Omega Memory with Curcumin by Nordic Naturals

Hyperlipidemia. Most research shows that taking oral DHA alone or with eicosapentaenoic acid (EPA) seems to modestly reduce triglyceride levels. However, DHA does not decrease total cholesterol and may increase levels of low-density lipoprotein (LDL) cholesterol. Details: Clinical research shows that taking DHA 1.25-4 grams daily for up to 7 weeks can reduce triglyceride levels by 17% to 24% in adult patients with mild hyperlipidemia, dyslipidemia, or hypertriglyceridemia (6143,48013,48338). Also, taking DHA-enriched fish oil providing DHA 810 mg plus EPA 210 mg daily for 8 weeks reduces triglyceride levels by 23% in premenopausal adults with mild hypertriglyceridemia (99131). Most clinical research suggests that DHA does not decrease total cholesterol (6143,48013,99131). Although some conflicting research exists, most research suggests that DHA modestly increases HDL cholesterol (6143,48013,48338,99131,109216). Most clinical research shows that DHA increases LDL cholesterol by about 8% to 13.6% (6143,48174,48338,109216). However, it may actually decrease levels of small, dense LDL particles (48174). There are conflicting results regarding the effects of DHA on cholesterol levels in children. One preliminary clinical study in children with primary hyperlipidemia shows that taking DHA 500 mg alone or along with EPA does not improve cholesterol levels when compared with control. However, this study was probably too small to detect statistically significant changes (90712). Other research in children aged 9 years and up with familial hypercholesterolemia or familial combined hyperlipidemia shows that taking DHA (DHASCO oil, Martek Biosciences Corp.) 1.2 grams daily for 6 weeks along with the National Cholesterol Education Program Step II (NCEP-II) diet actually increases total cholesterol and LDL cholesterol when compared to following the diet alone (48078,48083). However, some clinical research shows that DHA increases the large buoyant type of LDL particles, but actually decreases the small, dense type (48083).
Preterm labor. Most research shows that oral DHA seems to prevent preterm labor in those with low DHA status at baseline. Details: A large clinical trial shows that taking DHA 1000 mg daily during pregnancy, starting at 12-20 weeks' gestation and continuing until delivery, results in an early preterm birth rate of 1.7%, compared with 2.4% in those taking DHA 200 mg daily. Benefits were strongest in those with low DHA status at baseline, with no benefit in those with high DHA status at baseline and in those with high adherence to DHA 1000 mg daily (109204,110360). A secondary analysis of two studies shows that taking DHA 800 mg from algal oil or 1000 mg from fish oil modestly reduces the early preterm and preterm birth rates in those with a low DHA status at baseline compared with taking DHA 200 mg (110361). However, conflicting evidence exists. Some clinical research shows that taking DHA during pregnancy does not reduce the risk of preterm delivery. One study has used a specific fish oil supplement (Incromega DHA 500TG) 900 mg containing DHA 800 mg and eicosapentaenoic acid (EPA)100 mg daily, starting at 20 weeks' gestation and continuing to delivery or 34 weeks' gestation (101505). In another clinical trial, use of a high-DHA fish oil, providing EPA 100 mg and DHA 800 mg daily, from before 20 weeks' until 34 weeks' gestation, increases the risk of preterm birth prior to 34 weeks' gestation when compared with placebo in patients with baseline omega-3 status of greater than 4.9%. However, the risk is reduced from 3.2% to 0.7% in patients with baseline omega-3 status below 4.1%. In addition, taking this high-DHA fish oil had no effect on the risk of preterm birth prior to 37 weeks' gestation (103496). The reasons for any discrepancies may be due to the baseline omega-3 status, the use of algal or fish oil as the source of DHA, and/or the specific timing of preterm labor.

POSSIBLY INEFFECTIVE

Age-related cognitive decline. Most research shows that taking oral DHA alone or with other ingredients does not slow or improve cognitive decline associated with age. Details: Most clinical research, from individual studies and a meta-analysis, shows that taking DHA orally, alone or with additional eicosapentaenoic acid (EPA) for up to 36 months, does not slow or improve age-related cognitive decline (97175,103313). In contrast, results from one large clinical study show that taking DHA 900 mg daily in the absence of EPA for 24 weeks improves episodic memory and visuospatial learning when compared with placebo in patients with age-related cognitive decline. However, DHA did not affect working memory or executive function (90717). DHA has also been evaluated in combination with other ingredients. A moderate-sized clinical study in older adults with subjective cognitive impairment and objective mild cognitive impairment shows that taking a DHA-rich fish oil containing DHA 1.1 grams and EPA 0.4 grams 3 times daily with high-flavanol cocoa for 12 months does not improve most measures of cognitive function, and moderately worsens reaction time variability, executive function, and alertness when compared with placebo. Additionally, there is no evidence of benefit on brain volumes, and patients who took DHA-rich fish oil and cocoa had greater decreases in cortical volume at 12 months when compared with placebo (111453).
Alzheimer disease. Taking oral DHA does not seem to slow Alzheimer disease progression. Details: Population research has found that a 0.1 gram per day increment of dietary DHA intake is associated with a 37% reduced risk of Alzheimer disease when taken for 2-21 years (15041,96527). However, a dose-response relationship was not seen, and a correlation between DHA blood concentration and dementia was not seen (96527). Furthermore, clinical research shows that taking DHA 2 grams daily for 18 months does not slow cognitive or functional decline in patients with mild to moderate Alzheimer disease (48290). DHA has also been examined in combination with other ingredients. Preliminary clinical research in patients with mild to moderate Alzheimer disease shows that taking DHA 500 mg, as part of fish 1 gram with eicosapentaenoic acid (EPA) 150 mg, and along with lutein 10 mg, zeaxanthin 2 mg, meso-zeaxanthin 10 mg, and vitamin E 15 mg (Memory Health) daily for 12 months does not affect disease severity when compared with placebo. However, there were modest increases the number of patients experiencing either an improvement or an attenuated decline in memory and mood (109764). The effect of DHA alone is unclear from this study.
Attention deficit-hyperactivity disorder (ADHD). Most research shows that taking oral DHA does not improve ADHD symptoms. Details: Low plasma levels of DHA are associated with ADHD in children (7599,15496). Although some preliminary clinical research shows that DHA might improve aggression, emotional problems, and social relationships in children with ADHD (15494,100940), taking DHA 345-500 mg daily or 3.6 grams weekly does not seem to improve objective or subjective measures of ADHD symptoms when compared with placebo (7599,15495,100940). DHA has also been evaluated in combination with other ingredients. A moderate-sized clinical study in drug-naïve children ages 6 to 12 years with mild to moderate ADHD shows that taking DHA 87 mg in combination with eicosapentaenoic acid (EPA) and gamma linoleic acid (GLA) daily for 12 months does not improve inattentive symptoms, global functioning, or learning skills when compared with placebo. There also does not appear to be a correlation between plasma fatty acid levels and ADHD symptoms (111058).
Bronchopulmonary dysplasia. Most research shows that oral DHA does not prevent bronchopulmonary dysplasia (BPD) in preterm infants. Some research suggests that it might increase the risk of BPD in infants born before 29 weeks gestation. Details: One meta-analysis of clinical research in over 3,500 preterm infants shows that administration of EPA and DHA as part of formula or as a direct oral dose, starting within one month of birth, does not increase or decrease the risk for BPD, regardless of the dose of DHA administered (102390). A more recent meta-analysis of four clinical trials limited to infants born less than 29 weeks gestation also shows that administration of DHA at levels of at least 40 mg/kg, or at levels of at least 0.4% total fatty acids in breast milk or formula, does not increase or decrease the risk of bronchopulmonary dysplasia (110359). However, in this latter meta-analysis, when only clinical trials using a more stringent definition of bronchopulmonary dysplasia were included, there was a modest INCREASED risk (110359). Similar findings occurred in a study that was terminated early. This research shows that maternal supplementation with DHA 1.2 grams daily, starting within 72 hours of delivery of infants born before 29 weeks gestation, has no effect on mortality of breastfed infants or survival without BPD at 36 weeks postmenstrual age. However, the occurrence of BPD and severe BPD in surviving infants of mothers taking DHA were increased when compared to those whose mothers took placebo (104559). The conclusions of this study are limited by the early termination, the provision of intravenous DHA-rich lipids to some infants per standard of clinical care, and the increased number of infants born via cesarean delivery to the mothers randomized to DHA. A more recent clinical trial has investigated the inclusion of arachidonic acid in an enteral emulsion providing DHA. One clinical trial in preterm infants born before 29 weeks gestation shows that supplementation with an enteral emulsion containing DHA 50 mg/kg and arachidonic acid 100 mg/kg (Formulaid, DSM Nutritional Products Inc.) until 36 weeks postmenstrual age does not increase the risk of bronchopulmonary dysplasia or other major morbidities compared to control (MCToil, Nutricia) emulsion. Also, infants given the arachidonic acid and DHA required 17 fewer days of respiratory support (110356).
Cognitive function. Most research shows that oral DHA does not improve cognitive function in healthy adults. Details: Most clinical research shows that taking DHA 250-1000 mg daily for up to 6 months does not improve cognitive function in healthy children, healthy adults, or older females (48194,48216,48266,90668,90708,104560). Also, cognitive function does not seem to be improved when compared with placebo in trials in which omega-3 products containing higher ratios of DHA to eicosapentaenoic acid (EPA) were used. These trials have used a specific product (Efamol Ltd) containing DHA 1.16 grams and EPA 0.17 grams daily (90707), DHA 900 mg plus EPA 270 mg (Accelon DHA EE, BASF) daily (109215), or fish oil (Dasbrain, Max Biocare) providing DHA 520 mg or 270 mg daily (109310), for 3 or 6 months in children and adults. However, some clinical research shows that taking algal oil containing DHA 600 mg daily for 16 weeks improves reading scores when compared with placebo in a subgroup of children ages 6-10 years who are below the 20th percentile for reading (90699). However, these results could not be replicated in a later study that included only children below the 20th percentile for reading (98542). The reason for this discrepancy is not clear. Taking DHA does not appear to improve reading scores in children at or above the 20th percentile for reading, and there does not appear to be any benefit of DHA on working memory in any children (90699).
Cystic fibrosis. Most research shows that oral DHA does not improve symptoms of cystic fibrosis. Details: Clinical research in infants, children, and young adults with cystic fibrosis shows that taking DHA (DHA-basic, CASEN Fleet SLU) 50 mg/kg daily for 48 weeks does not improve spirometry measures, reduce Pseudomonas aeruginosa primary infections, or reduce the number of, or time to, total or severe pulmonary exacerbations when compared with placebo (109217). Also, small clinical studies show that taking DHA 70 mg/kg daily for 6 weeks, or 100 mg/kg daily for one month and then 1 gram daily for 11 months, does not improve lung function or overall health in patients with cystic fibrosis (48119,90665).
Depression. Most research shows that oral DHA does not improve depression, regardless of the type. Details: Taking DHA orally does not seem to relieve symptoms of major depression, peripartum depression, or postpartum depression in most patients (10869,48030,48238,90680,90691,90692,89353,102391). Also, taking DHA for two weeks prior to the start of interferon-alpha therapy does not appear to prevent depression during interferon-alpha treatment in patients with hepatitis C, although it may delay depression onset by about 6 weeks (90710).
Macrosomia. Taking oral DHA during pregnancy does not seem to prevent fetal macrosomia. Details: Clinical research in overweight or obese individuals shows that taking DHA (S-oil, DSM Nutritional Products) 800 mg daily, starting before 15 weeks' gestation and continuing until delivery, with or without dietary counselling, does not reduce the incidence of macrosomia when compared with taking DHA 200 mg daily (109218).

Age-related macular degeneration (AMD). Oral DHA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Increased dietary consumption of DHA is associated with a decreased risk of AMD (10324). Preliminary clinical research shows that taking a combination of DHA 280 mg, lutein 12 mg, and zeaxanthin 0.6 mg daily for one year increases macular pigment optical density by 31% when compared with placebo in patients with AMD. Increased macular pigment optical density is associated with improve vision performance and a reduced risk of AMD (90678). However, other clinical research suggests that adding DHA plus EPA to an AREDS formula, with or without lutein and zeaxanthin, does not reduce the time to development of AMD or vision loss in patients at high risk of progression to advanced AMD when compared with the AREDS formula alone (60281).
Allergic rhinitis (hay fever). Although there has been interest in using oral DHA for allergic rhinitis, there is insufficient reliable information about the clinical effects of DHA for this condition.
Atopic dermatitis (eczema). It is unclear if adding DHA to infant formula prevents atopic dermatitis. Details: Evidence from an observational, open-label study shows that giving full-term infants formula with added DHA 17 mg/100 kcal and arachidonic acid 34 mg/100 kcal (Enfamil Premium 1 and Enfamil Premium 2, Mead Johnson Nutrition) as needed for 12 months does not prevent the development of eczema when compared to control formulas without DHA and arachidonic acid (92505).
Atopic disease. It is unclear if oral DHA during pregnancy prevents atopic disease in the infant. Details: Clinical research shows that supplementation with DHA during pregnancy may modestly protect against some respiratory symptoms in the infants of atopic mothers. Prenatal supplementation with DHA 400 mg, taken daily from 18-22 weeks gestation until delivery, reduces the incidence of phlegm with nasal discharge or nasal congestion in the infant by the age of 18 months by approximately 22% and the incidence of fever with phlegm and nasal discharge or nasal congestion in the infant by approximately 47% when compared with placebo (90676). However, it is unclear if these symptoms are due to atopy or infections.
Atrial fibrillation. Oral DHA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Population research suggests that adipose tissue levels of DHA are not associated with a decreased risk of atrial fibrillation (90700). However, clinical research suggests that taking 2 grams per day of a combination of DHA plus EPA (2:1 ratio), starting 7 days before cardiac surgery and continuing until hospital discharge, reduces the relative risk of post-cardiac surgery atrial fibrillation by 72% when compared with placebo. These patients also received vitamin C 1 gram daily plus vitamin E 400 IU daily, starting 2 days prior to surgery and continuing until discharge (90701).
Autism spectrum disorder. It is unclear if oral DHA is beneficial for autism. Details: One preliminary clinical study shows that taking DHA 200 mg daily for 6 months does not improve autism symptoms in children and may even worsen some behaviors (90713). Another preliminary clinical study in children and adults with autism shows that taking a specific product (SUNTGA40S, Aravita, Suntory Ltd) containing DHA, arachidonic acid, and astaxanthin daily for 16 weeks does not improve overall symptoms when compared with placebo, although the combination product may improve certain symptoms such as social withdrawal or social communication (90716).
Behcet disease. Although there has been interest in using oral DHA for Behcet disease, there is insufficient reliable information about the clinical effects of DHA for this condition.
Bipolar disorder. It is unclear if oral DHA is beneficial for bipolar disorder in adults. Details: A small clinical trial shows that taking DHA 1250 mg daily for 12 weeks does not improve cognitive function when compared with placebo in patients with bipolar disorder (103312).
Breast cancer. It is unclear if oral DHA is beneficial for breast cancer treatment or prevention. Details: Population research has found no association between dietary fatty acid intake, including DHA, and the risk of breast cancer (96528). The effect of DHA supplementation on breast cancer risk is unknown. Some early research has investigated the effects of DHA in patients with breast cancer. Preliminary clinical research shows that taking DHA (DHASCO, Martek Biosciences Corp.) 600 mg three times daily for 7-10 days prior to chemotherapy initiation, and then for 5 months during chemotherapy, induces complete or partial response in 44% of breast cancer patients. Patients with a greater increase in DHA levels (at least 2.5%) show a longer time to progression and longer survival when compared to those with a smaller increase in DHA levels (90671).
Cancer. Taking oral DHA with oral eicosapentaenoic acid (EPA) does not seem to decrease the risk of cancer in patients with cardiovascular disease and may actually INCREASE the risk of cancer in females. The effect of DHA alone is unclear. Details: Clinical research suggests that taking a combination of EPA 400 mg plus DHA 200 mg, with or without B vitamins, for a median of 4.7 years does not reduce the risk of cancer in middle-aged and elderly patients with cardiovascular disease. Furthermore, this combination appears to increase the risk of cancer in females (90666).
Child development. It is unclear if oral DHA is beneficial for child development. However, due to the lack of significant safety concerns and the possibility of some cognitive benefit, many experts recommend DHA 200 mg daily during pregnancy. Details: Clinical research shows that giving infants DHA-supplemented formula during infancy does not appear to improve language and school readiness by the age of 2-3.5 years, or improve neurodevelopment by the age of 6 years (90674,92503). In addition, most research suggests that DHA supplementation during pregnancy, occasionally continuing postpartum for 6 months, does not affect visual acuity, attention, working memory, behavior and most other measures of neurodevelopment by 1-7 years of age (48095,48285,48293,90679,90690,94600,96522,109219). There is some evidence to suggest that maternal supplementation with DHA 400 mg daily from 16 weeks gestation until delivery may reduce the risk of poor language development in the infant at age 14 and 18 months and the risk of lower visual acuity at 2 months when compared with placebo (90694); however, this benefit did not have lasting effects at 5-6 years of age (99133).
Cognitive impairment. It is unclear if oral DHA is beneficial for cognitive impairment in older adults. Details: Clinical research shows that taking DHA 800 mg daily, alone or with folic acid 800 mcg daily for 6 months, modestly improves some measures of cognitive function when compared with placebo in elderly patients with mild cognitive impairment (103978). Also, taking a specific product (Vayacog, Enzymotec Ltd.) providing phosphatidylserine 300 mg, DHA about 59 mg, and eicosapentaenoic acid (EPA) about 20 mg daily for 15 weeks improves verbal immediate recall when compared with placebo (94665). However, other research in older patients with mild cognitive impairment disagrees. Several clinical studies show that taking DHA 720-3300 mg plus EPA 351-1200 mg daily and other ingredients such as cocoa for 12 weeks to 12 months does not improve cognitive measures including memory and forgetfulness when compared with placebo (62847,90704,94665,109220,111453). One moderate-sized clinical study in older adults with subjective cognitive impairment and mild cognitive impairment shows that taking DHA 1.1 grams and EPA 0.4 grams 3 times daily with high-flavanol cocoa for 12 months moderately worsens reaction time variability, executive function, and alertness when compared with placebo. Additionally, there is no evidence of benefit on brain volumes, and those taking DHA-rich fish oil and cocoa had a greater decrease in cortical volume at 12 months when compared with placebo (111453).
Coronary heart disease (CHD). It is unclear if oral DHA is beneficial for CHD. Details: Increased dietary consumption of DHA may reduce the risk of death in patients with CHD (10322). However, the effect of DHA supplements is unclear.
Crohn disease. It is unclear if oral DHA is beneficial for Crohn disease prevention. Details: Population research suggests that increased dietary intake of DHA is associated with a reduced risk of Crohn disease (90673).
Dementia. It is unclear if oral DHA is beneficial for dementia prevention. Details: Population research has found that a 0.1 gram per day increment of dietary DHA intake is associated with a 14% reduced risk of dementia when taken for 2-21 years. However, a dose-response relationship was not seen, and a correlation between DHA blood concentration and dementia was not seen (96527).
Developmental coordination disorder (DCD). Oral DHA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children with DCD shows that taking a tuna fish oil product providing DHA 480 mg daily for 4 months, in combination with evening primrose oil providing arachidonic acid 35 mg and gamma-linolenic acid 96 mg, thyme oil 24 mg, and vitamin E 80 mg (Efalex, Efamol Ltd.), modestly decreases movement disorders as determined by objective measures when compared with baseline (5708). It is unclear if these benefits are due to DHA, other ingredients, or the combination. Also, the validity of this finding is limited by the lack of a comparator group.
Diabetes. It is unclear if oral DHA is beneficial for glycemic control or the prevention of type 1 or gestational diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking DHA orally does not improve levels of low-density lipoprotein (LDL) cholesterol or decrease blood sugar or glycated hemoglobin. However, triglyceride levels are reduced (10321). DHA has also been evaluated for the prevention of gestational or type 1 diabetes. Clinical research in overweight or obese individuals shows that taking DHA (S-oil, DSM Nutritional Products) 800 mg daily, starting before 15 weeks' gestation and continuing until delivery, with or without dietary counselling, does not reduce the incidence of gestational diabetes when compared with taking DHA 200 mg daily (109218). Additionally, population research suggests that maternal serum levels of DHA are not associated with the risk of childhood onset of type 1 diabetes (90705).
Diabetic retinopathy. Oral DHA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with diabetic macular edema related to diabetic retinopathy receiving ranibizumab shows that taking a combination supplement containing DHA 1050 mg daily along with other free fatty acids, minerals, and vitamins (Brudyretina, Brudy Lab S.L.) for 2 years reduces macular thickness, but not visual acuity, when compared with ranibizumab alone. The effect of DHA alone is unknown (96526).
Diarrhea. It is unclear if infant formula containing DHA is beneficial for diarrhea prevention. Details: Preliminary clinical research suggests that giving full-term infants formula with added DHA 17 mg/100 kcal and arachidonic acid 34 mg/100 kcal (Enfamil Premium 1 and Enfamil Premium 2, Mead Johnson Nutrition) as needed for 12 months reduces the incidence of diarrhea requiring medical attention when compared to control formulas (92505).
Dyslexia. It is unclear if oral DHA is beneficial for improving night vision in children with this condition. Details: One small clinical study in children with dyslexia shows that taking fish oils rich in DHA, providing 480 mg daily for one month, seem to develop significantly better dark adaptation when compared with controls (5708).
Dysmenorrhea. Although there has been interest in using oral DHA for dysmenorrhea, there is insufficient reliable information about the clinical effects of DHA for this condition.
Fractures. Oral DHA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study shows that taking omega-3 fatty acids 1 gram daily, providing DHA 660 mg and eicosapentaenoic acid (EPA) 330 mg, for 3 years does not prevent fractures in adults over 70 years of age when compared with placebo. These findings were consistent in adults taking omega-3 fatty acids alone or combined with vitamin D 2000 IU daily and/or strength training three times weekly (104619).
Glaucoma. Oral DHA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in older adults with glaucoma shows that taking DHA 1.5 grams 3 times daily with citicoline for 3 months reduces the amount and rate of visual field loss and improves visual field index but does not reduce intraocular pressure when compared to baseline (112236). It is unclear if these effects are due to DHA, citicoline, or the combination; however, since no effects were found in the groups administered DHA or citicoline alone, it is possible that the effects are due to the combination of ingredients. The validity of these effects is limited by a lack of a control group and the very small sample size.
Hypertension. It is unclear if oral DHA is beneficial for reducing blood pressure in adults or if prenatal supplementation reduces blood pressure in children. Details: Clinical research shows that taking DHA-enriched canola oil containing 63% oleic acid and 6% DHA for 4 weeks reduces systolic blood pressure by 3% and diastolic blood pressure by 4% when compared to baseline in adults with at least one cardiovascular risk factor (26466). A meta-analysis of clinical research in adults with dyslipidemia shows that supplemental DHA reduces diastolic, but not systolic, blood pressure when compared with control (102389). A large clinical study shows that taking omega-3 fatty acids 1 gram daily, providing DHA 660 mg and eicosapentaenoic acid (EPA) 330 mg, for 3 years does not reduce blood pressure levels in adults over 70 years of age when compared with placebo. These findings were consistent in adults taking omega-3 fatty acids alone or combined with vitamin D 2000 IU daily and/or strength training three times weekly. About 39% of the individuals included in this study were diagnosed with hypertension and about 50% were using antihypertensives (104619). The effect of DHA alone on blood pressure levels in a population of adults with diagnosed hypertension is unclear. Prenatal supplementation with DHA has also been evaluated for the prevention of hypertension in children. A secondary analysis of a large clinical trial shows that overweight children or children with obesity whose mothers took DHA 600 mg daily, starting at about 14.5 weeks' gestation and continuing until birth, have lower diastolic and systolic blood pressure at 5 years of age when compared with those whose mothers took placebo. Systolic and diastolic blood pressure were reduced by about 4 mm Hg and 5 mm Hg, respectively, in the children exposed to DHA during pregnancy when compared with those exposed to placebo. The blood pressure of the children exposed to DHA during pregnancy was similar to that of children with normal weight (98891). Results of this study are limited by the fact that confounding factors, such as shorter duration of breast-feeding and increased sodium intake for children with obesity in the placebo group, may have also contributed to differences in blood pressure. It is unclear if this reduction in elevated blood pressure during childhood reduces the risk of hypertension in adulthood.
IgA nephropathy. Although there has been interest in using oral DHA for IgA nephropathy, there is insufficient reliable information about the clinical effects of DHA for this condition.
Infant development. Infant supplementation with DHA does not seem to improve development. Also, most evidence shows that maternal supplementation with DHA is not beneficial for infant cognitive development. However, due to the lack of significant safety concerns and the possibility of some cognitive benefit, many experts recommend DHA 200 mg daily during pregnancy. Details: Most clinical research shows that giving healthy, full-term infants formula supplemented with DHA 0.32% to 0.96% modestly improves measures of visual acuity at 2, 4, and 12 months of age when compared with standard infant formula (14403,15003,47980,48355,90670). However, formula supplemented with DHA 0.15% does not appear to improve visual acuity by about 12 months when given to preterm infants (48008). There is some evidence that giving healthy, full-term infants DHA-supplemented formula during infancy might improve language comprehension and development, as well as fine motor skills, by the age of 12-14 months when compared with standard formula (48247,48356). However, most clinical research, including meta-analyses of high-quality clinical trials, shows that giving infants formula supplemented with DHA during infancy does not improve overall cognition or motor skills at 12-14 months of age, regardless of DHA dosing or prematurity status (48247,48356,89363). Experts generally recommend breast-feeding as the preferred feeding method over DHA-supplemented formula; however, if formula is used, some experts suggest a formula providing at least 0.2% of lipids from DHA (14403). Some population research suggests that higher maternal DHA levels are associated with improved use of gestures and problem solving in infants (90709,99132). However, population research suggests that higher maternal DHA levels also appear to be associated with worsening mental development (90709), and most clinical research shows that maternal ingestion of DHA has little effect on fetal or infant development. Maternal ingestion of DHA 33-133 mg daily from an egg source or 400 mg daily from an algal-based source does not seem to significantly increase weight, length, or head circumference at birth (14395,48286). Also, maternal ingestion of DHA 200-400 mg daily from week 15-22 of pregnancy until term does not significantly improve visual or auditory development in term infants (14393,90706). A small clinical trial shows that taking DHA 1440 mg daily from fish oil also providing eicosapentaenoic acid (EPA) 260 mg, from 22-24 weeks gestation until delivery, does not improve most measures of developmental or behavioral milestones in the infant at 6 months, when compared with olive oil placebo (110354). In addition, most research suggests that DHA supplementation during pregnancy, occasionally continuing postpartum for 6 months, does not affect growth to age 18 months or visual acuity, attention, working memory, behavior and most other measures of neurodevelopment by 1-7 years of age (48095,48285,48293,90679,90690,94600,96522,109219). However, there is some evidence to suggest that maternal supplementation with DHA 214 mg daily may improve infant sleep patterning on the first day of life (90687). Also, maternal supplementation with DHA 400 mg daily from 16 weeks gestation until delivery may reduce the risk of poor language development in the infant at age 14 and 18 months and the risk of lower visual acuity at 2 months when compared with placebo (90694). However, this benefit did not have lasting effects at 5-6 years of age (99133).
Intraventricular hemorrhage. It is unclear if oral DHA is beneficial for preventing intraventricular hemorrhage in premature infants. Details: Preliminary clinical research in infants born before 29 weeks gestation shows that supplementation with an enteral emulsion containing DHA 50 mg/kg and arachidonic acid 100 mg/kg (Formulaid, DSM Nutritional Products Inc.) until 36 weeks postmenstrual age has no effect on the incidence of intraventricular hemorrhage when compared with a control emulsion (110356).
Keratoconus. It is unclear if oral DHA is beneficial for improving vision in people with keratoconus. Details: A small clinical trial in patients with early to advanced keratoconus shows that taking DHA 1000 mg daily for 3 months does not improve corneal thickness, measurements of corneal curve, or most other ophthalmological measures when compared with taking no DHA (110358).
Lower respiratory tract infections. It is unclear if formula containing DHA is beneficial for preventing lower respiratory tract infections in infants. Details: Clinical research shows that giving preterm infants formula or breast milk containing high-dose DHA (1% of fatty acids) does not prevent hospitalizations due to bronchiolitis and other lower respiratory tract conditions when compared with giving breast milk or formula containing 0.35% DHA (90667). However, preliminary clinical research shows that giving full-term infants formula with added DHA 17 mg/100 kcal and arachidonic acid 34 mg/100 kcal (Enfamil Premium 1 and Enfamil Premium 2, Mead Johnson Nutrition) as needed for 12 months reduces the risk of bronchiolitis and croup when compared with control formulas (92505).
Male infertility. It is unclear if oral DHA is beneficial for improving fertility. Details: Clinical research shows that taking DHA (NuaDHA, Nua Biological Innovations SL) 0.5, 1, or 2 grams daily for 3 months increases progressive sperm motility by 24% to 30% when compared with placebo in men with a history of infertility. The greatest effects were seen in men with asthenozoospermia, with an overall effect of 35 (99134). It is unclear if the effects of DHA on sperm function correlate with increased fertility rates.
Metabolic syndrome. Although there has been interest in using oral DHA for metabolic syndrome, there is insufficient reliable information about the clinical effects of DHA for this condition.
Migraine headache. Although there has been interest in using oral DHA for migraine headache, there is insufficient reliable information about the clinical effects of DHA for this condition.
Muscle strength. It is unclear if oral DHA is beneficial for increasing muscle strength. Details: A large clinical study shows that taking omega-3 fatty acids 1 gram daily, providing DHA 660 mg and eicosapentaenoic acid (EPA) 330 mg, for 3 years does not increase muscle strength in adults over 70 years of age when compared with placebo. These findings were consistent in adults taking omega-3 fatty acids alone or combined with vitamin D 2000 IU daily and/or strength training three times weekly (104619).
Necrotizing enterocolitis (NEC). It is unclear if oral DHA is beneficial for preventing NEC in preterm infants. Details: Clinical research in preterm infants shows that providing DHA (Neuromins for Kids life's DHA; DSM Nutritional Products Inc.) 75 mg/kg for 14 days from the first enteral feed reduces the risk of confirmed NEC by 7% when compared with a control oil. Treatment of 15 infants with DHA would be needed to prevent one case of NEC (109213). However, preliminary clinical research shows that maternal supplementation with DHA 1.2 grams daily, starting within 72 hours of delivery of infants born before 29 weeks' gestation, has no effect on the incidence of NEC in breastfed infants at 36 weeks postmenstrual age when compared with placebo (104559). Other preliminary clinical research in infants born before 29 weeks gestation shows that supplementation with an enteral emulsion containing DHA 50 mg/kg and arachidonic acid 100 mg/kg (Formulaid, DSM Nutritional Products Inc.) until 36 weeks postmenstrual age has no effect on the incidence of NEC when compared with a control emulsion (110356).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral DHA is beneficial for NAFLD. Details: Preliminary clinical research shows that taking DHA (Martek Biosciences Corporation) 250-500 mg daily for 6-24 months reduces the risk of severe liver steatosis when compared with placebo in children with NAFLD (48295,90695,90696).
Obesity. It is unclear if oral DHA is beneficial for improving weight loss in overweight or obese adults. Details: Preliminary clinical research shows that taking 2.8 grams daily of an oil emulsion containing approximately 46% DHA for 12 weeks decreases carbohydrate and fat intake, but does not reduce body weight or improve body composition, when compared with placebo in overweight or obese adults (90681).
Otitis media. It is unclear if DHA in infant formula is beneficial for preventing otitis media in infants. Details: Preliminary clinical research shows that giving full-term infants formula with added DHA 17 mg/100 kcal and arachidonic acid 34 mg/100 kcal (Enfamil Premium 1 and Enfamil Premium 2, Mead Johnson Nutrition) for 12 months does not prevent the development of ear infection when compared with control formulas (92505).
Phenylketonuria (PKU). It is unclear if oral DHA is beneficial for PKU. Details: Children with PKU consume very low amounts of DHA. Clinical research shows that taking DHA up to approximately 7 mg/kg daily for 6 months improves DHA status, but not neurological function, in children aged 5-13 years with PKU (99631). The effect of higher doses of DHA, or the effect of DHA supplementation on neurological function in younger children with PKU, have not been determined.
Physical performance. It is unclear if oral DHA is beneficial for increasing physical performance in older adults. Details: A large clinical study shows that taking omega-3 fatty acids 1 gram daily, providing DHA 660 mg and eicosapentaenoic acid (EPA) 330 mg, for 3 years does not improve physical performance in adults over 70 years of age when compared with placebo. These findings were consistent in adults taking omega-3 fatty acids alone or combined with vitamin D 2000 IU daily and/or strength training three times weekly (104619).
Postoperative pain. It is unclear if oral DHA is beneficial for reducing postoperative analgesic use. Details: A post-hoc analysis shows that enteral DHA 75 mg/kg administered perioperatively to infants born at greater than 34 weeks gestation who are undergoing cardiac surgery reduces the cumulative analgesic dose and shortens the duration of buprenorphine during the postoperative period when compared with placebo. However, the use of fentanyl or ketorolac were not reduced (96524).
Prematurity. It is unclear if oral DHA during lactation or in early infancy is beneficial for increasing growth or neurodevelopment of the premature infant. Details: Clinical research in lactating individuals who delivered prior to 29 weeks' gestation shows that taking DHA 1.2 grams daily, starting within 72 hours of delivery and continuing until the infant reached 36 weeks postmenstrual age, might have beneficial effects on the growth of female infants, but not male infants, when compared with placebo. Weight velocity and weight gain were significantly increased in the female infants, with a weight gain of 52.6 grams. However, weight gain and weight velocity were not improved in the male infants, and weight at 36 weeks postmenstrual age was 89 grams less than those whose mothers took placebo (109221). In addition, there was no improvement in neurodevelopmental outcomes at 18 to 22 months corrected age (110364). Other clinical research in infants born before 29 weeks' gestation shows that giving enteral DHA 60 mg/kg daily until 36 weeks corrected gestational age does not improve most measures of intelligence at 5 years when compared with placebo (110363). However, a cohort study in premature infants born before 29 weeks' gestation suggests that supplementation with enteral high-dose DHA emulsion 60 mg/kg daily to match in-utero requirements until 36 weeks' gestational age or discharge home is associated with an increased risk of bronchopulmonary dysplasia and a 3.45 point benefit in intelligence quotient (IQ) at 5 years' corrected age. Further analysis of this relationship suggests that the increased risk effect of bronchopulmonary dysplasia from neonatal high-dose DHA is not associated with a decrease in the beneficial effects of DHA on IQ (112238).
Prostate cancer. It is unclear if oral DHA is beneficial for prostate cancer prevention. Details: Observational research has found that higher consumption of DHA is associated with a reduced risk of total, advanced, and aggressive prostate cancer when compared to lower consumption of DHA (12961,25937). However, a meta-analysis of multiple population studies has found that higher DHA blood levels are associated with a 2.5-fold higher risk of aggressive prostate cancer, but not low-grade prostate cancer, when compared with lower blood percentages of DHA (25936). Another meta-analysis of population research has found that a higher blood level of DHA is associated with a slight increased risk of non-aggressive prostate cancer (90677).
Psoriasis. Although there has been interest in using oral DHA for psoriasis, there is insufficient reliable information about the clinical effects of DHA for this condition.
Raynaud syndrome. Although there has been interest in using oral DHA for Raynaud syndrome, there is insufficient reliable information about the clinical effects of DHA for this condition.
Restenosis. It is unclear if oral DHA is beneficial for preventing restenosis in people with stents. Details: Observational research has found that initiation of statin therapy in patients receiving stent placement after an acute coronary event is associated with a reduction in DHA levels. These reductions in DHA are associated with a greater prevalence of in-stent restenosis. From these results, researchers postulate that patients newly started on a statin after stent placement for acute coronary syndrome might benefit from DHA supplementation (100939). However, the effect of DHA supplementation is unknown.
Retinitis pigmentosa. Evidence for the use of oral DHA for retinitis pigmentosa is inconsistent and contradictory. Details: Some clinical research shows that taking DHA 1200 mg daily for 4 years does not improve eye function in patients with retinitis pigmentosa who are also taking vitamin A when compared with placebo (48070). Also, taking DHA 600-3600 mg daily for 4 years does not maintain rod or cone function in boys or men with retinitis pigmentosa when compared with placebo (90683). However, a report of ancillary outcomes from this study shows that taking DHA might slow the rate of decline in final dark-adapted thresholds and visual field sensitivity in these patients (95738). Also, some research shows that taking DHA 400 mg daily for 4 years does maintain rod and cone function in some patients, although visual function is not improved when compared with placebo (48057,48115).
Retinopathy of prematurity. It is unclear if maternal or infant supplementation with oral DHA is beneficial for preventing retinopathy of prematurity. Details: Preliminary clinical research shows that maternal supplementation with DHA 1.2 grams daily, starting within 72 hours of delivery of infants born before 29 weeks gestation, has no effect on the incidence of retinopathy of prematurity in breastfed infants at 36 weeks postmenstrual age when compared with placebo (104559). Other preliminary clinical research in infants born before 29 weeks gestation shows that supplementation with an enteral emulsion containing DHA 50 mg/kg and arachidonic acid 100 mg/kg (Formulaid, DSM Nutritional Products Inc.) until 36 weeks postmenstrual age has no effect on the incidence of retinopathy of prematurity when compared with a control emulsion (110356).
Rheumatoid arthritis (RA). Although there has been interest in using oral DHA for RA, there is insufficient reliable information about the clinical effects of DHA for this condition.
Schizophrenia. Oral DHA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking EPA 1000 mg, DHA 500 mg, and alpha-lipoic acid 150 mg twice daily for up to 2 years after discontinuing antipsychotic treatment does not prevent relapse in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder (90675).
Sepsis. It is unclear if oral DHA is beneficial for preventing sepsis in premature infants. Details: Preliminary clinical research shows that maternal supplementation with DHA 1.2 grams daily, starting within 72 hours of delivery of infants born before 29 weeks gestation, has no effect on the incidence of sepsis in breastfed infants at 36 weeks postmenstrual age when compared with placebo (104559). Other preliminary clinical research in infants born before 29 weeks gestation shows that supplementation with an enteral emulsion containing DHA 50 mg/kg and arachidonic acid 100 mg/kg (Formulaid, DSM Nutritional Products Inc.) until 36 weeks postmenstrual age has no effect on the incidence of sepsis when compared with a control emulsion (110356).
Sickle cell disease. It is unclear if oral DHA is beneficial for treating sickle cell disease. Details: A very small clinical study in adults with sickle cell disease shows that eating mayonnaise enriched with DHA 1900 mg and eicosapentaenoic acid (EPA) daily for 28 days does not reduce vaso-occlusive crisis pain or biomarkers of systemic inflammation (112237). The validity of these effects is limited by a lack of a comparator group and a very small sample size.
Spinocerebellar ataxia (SCA). It is unclear if oral DHA is beneficial for SCA. Details: Preliminary clinical research in patients with SCA shows that taking DHA 600 mg daily for 16 weeks reduces ataxia and improves cerebellar hypometabolism upon brain imaging when compared with placebo. These beneficial effects are sustained when DHA is taken for an additional 40 weeks (96525).
Stroke. It is unclear if oral DHA is beneficial for stroke prevention. Details: Population research has found that serum DHA levels may be associated with a reduced risk of ischemic stroke, as well as any specific type of ischemic stroke, including cardioembolic stroke, atherothrombotic stroke, and lacunar stroke (90715).
Systemic lupus erythematosus (SLE). Although there has been interest in using oral DHA for SLE, there is insufficient reliable information about the clinical effects of DHA for this condition.
Systemic lupus erythematosus (SLE) nephritis. Although there has been interest in using oral DHA for SLE nephritis, there is insufficient reliable information about the clinical effects of DHA for this condition.
Ulcerative colitis. Although there has been interest in using oral DHA for ulcerative colitis, there is insufficient reliable information about the clinical effects of DHA for this condition.
Vascular dementia. It is unclear if DHA is beneficial for improving dementia severity. Details: Preliminary clinical research in patients with vascular dementia shows that taking DHA 0.72 grams daily for one year improves dementia severity based on the Hasegawa's Dementia Rating Scale and Mini-Mental State Examination Scale scores when compared to baseline (47940). More evidence is needed to rate DHA for these uses.

EICOSAPENTAENOIC ACID (EPA) (Eicosapentaenoic Acid)

EFFECTIVE

Hypertriglyceridemia. Oral prescription ethyl-EPA 4 grams daily reduces triglyceride levels in patients with hypertriglyceridemia, especially in severe cases. It is unclear if oral EPA supplements are beneficial in hypertriglyceridemia. Details: A specific ethyl-EPA product (Vascepa, formerly ARM101, Amarin) is approved by the US Food and Drug Administration (FDA) to be used at a dose of 4 grams daily with diet modification to reduce triglyceride levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia. Clinical research shows that taking 4 grams daily in two divided doses for 12 weeks reduces triglyceride levels by 33%, total cholesterol by 16%, very low-density lipoprotein (VLDL) cholesterol by 29%, and apolipoprotein B by 9% when compared with placebo (91410). In patients taking statins with persistent elevated triglyceride levels (between 200 mg/dL and 500 mg/dL), this prescription product reduces triglyceride levels by about 22% and low-density lipoprotein (LDL) cholesterol by about 6% when compared with placebo (91409). In females with diabetes taking statins with persistent elevated triglyceride levels, this product reduces triglyceride levels by about 21.5% and total cholesterol levels by 12.5%, but does not reduce levels of LDL cholesterol when compared with placebo (99136). Furthermore, a large clinical trial (REDUCE-IT) in patients with LDL cholesterol levels controlled with statin therapy, but with persistent elevated triglyceride levels and other cardiovascular risk factors, shows that this product reduces the risk of major adverse cardiovascular events by 25% when compared with placebo after a median follow-up of 4.9 years. The number of these patients needed to be treated to prevent one major adverse cardiovascular event is 21 (95715). Preliminary clinical research in patients with hypertriglyceridemia also shows that taking a specific self-emulsifying ethyl-EPA (MND-2119, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan) 2 grams or 4 grams once daily for 52 weeks reduces levels of triglycerides by 16.7% and 21.0%, respectively, compared with baseline (110365). This study is uncontrolled and open-label. There is no strong evidence that EPA SUPPLEMENTS reduce triglyceride levels in patients with hypertriglyceridemia.

Cardiovascular disease (CVD). Oral prescription ethyl-EPA seems to reduce the risk of CVD events when used as an adjunct to statin therapy in patients with CVD risk. It is unclear if oral EPA supplements are beneficial in CVD. Details: A specific ethyl EPA product (Vascepa, Amarin) is approved by the US Food and Drug Administration (FDA) to be used as an adjunct to statin therapy to reduce the risk of cardiovascular events such as myocardial infarction and stroke in adult patients with elevated triglycerides (≥ 150 mg/dL) and CVD or diabetes mellitus and at least two additional risk factors for CVD (101286). This approval was mostly due to evidence from a large clinical trial (REDUCE-IT). For patients in the REDUCE-IT trial on statin therapy with persistent elevated triglyceride levels and other cardiovascular risk factors, taking Vascepa 4 grams daily reduced the risk of major adverse cardiovascular events by 25% when compared to placebo after a median follow-up of 4.9 years. To prevent one major cardiovascular event, 21 patients need to be treated (95715). There is no strong evidence that EPA SUPPLEMENTS reduce CVD risk in patients with hypertriglyceridemia.
Depression. Oral EPA seems to reduce symptoms of depression, especially in patients already being treated with conventional antidepressants. Details: Meta-analyses of clinical research show that pure EPA or omega-3 fatty acid enriched in EPA (at least 60%) moderately reduces depressive symptoms in patients with major depressive disorder (MDD) and those with depressive symptomatology but no diagnosis of MDD (90680,66129,102391). The beneficial effect of EPA appears to be dose-dependent in patients with MDD but not in those with depressive symptomatology (90680). The duration of treatment and the age of the patients do not appear to influence the effects of EPA (66129). Patients already being treated with conventional antidepressant medications may benefit more from EPA than those not taking antidepressants. Preliminary clinical research shows that taking ethyl-EPA orally 500 mg to 1 gram twice daily with standard therapy improves symptoms of recurrent major depression, such as depressed mood, guilty feelings, worthlessness, and insomnia, after 2-4 weeks of treatment (10215,10872). A 1 gram per day dose of ethyl-EPA may be more effective for depression than 2 grams per day (10215). However, in patients not using standard therapy, taking EPA-enriched omega-3 fatty acid (ProEPA Xtra, NordicNaturals) standardized to contain EPA 1060 mg and docosahexaenoic acid (DHA) 274 mg daily for 8 weeks does not reduce symptoms of depression in patients with MDD (90691). Some research suggests that EPA may help prevent the development of major depression in patients treated with interferon-alpha. Clinical research shows that only 10% of patients taking EPA 3.5 grams daily for 2 weeks prior to the start of interferon-alpha therapy experience major depression during the 24 weeks of interferon-alpha treatment compared to 30% of patients taking placebo. Also, the onset of depression is delayed from approximately 5.3 weeks to 12 weeks (90710). Based on these and other findings, Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that omega-3 fatty acids providing 1-2 grams EPA are recommended for adjunctive use in patients with major depressive disorder. However, omega-3 fatty acids are not recommended as monotherapy and products containing other doses of EPA are not recommended as adjunctive or monotherapy in these patients (110318).
Myocardial infarction (MI). Oral prescription ethyl-EPA reduces the risk of MI when used as an adjunct to statin therapy in patients with cardiovascular disease (CVD) risk. Oral EPA supplements also seem to be beneficial for this purpose. Details: A specific ethyl-EPA product (Vascepa, Amarin) 4 grams daily is approved by the US Food and Drug Administration (FDA) to be used as an adjunct to statin therapy to reduce the risk of cardiovascular events such as myocardial infarction and stroke in adult patients with elevated triglycerides (≥ 150 mg/dL) and CVD or diabetes mellitus and at least two additional risk factors for CVD (101286). The effects of EPA SUPPLEMENTS for MI are less clear. Clinical research in patients with acute MI shows that taking EPA 1.8 grams daily along with pitavastatin 2 mg daily for one month starting within 24 hours of percutaneous coronary intervention (PCI) reduces the incidence of adverse cardiac events, including cardiac death, stroke, re-infarction, ventricular arrhythmias, and paroxysmal atrial fibrillation, by 64% when compared with pitavastatin alone. In particular, the incidence of ventricular arrhythmias is reduced by about 66% for patients treated with EPA plus pitavastatin compared to pitavastatin alone (91411). Taking this same dose of EPA along with the same dose of pitavastatin for one year after PCI in patients with acute MI also reduces the absolute risk of cardiovascular death, MI, stroke, or coronary revascularization by 11% when compared to pitavastatin alone. The reduction in cardiovascular events after one year was largely due to a decrease in cardiovascular deaths by about 6% (96420). There is also evidence that taking EPA 1.8 grams daily along with pitavastatin 4 mg daily for 6-8 months following PCI for acute coronary syndrome reduces plaque lipid volume by 20% when compared to pitavastatin alone (96419). One clinical study also shows that taking EPA 0.9 grams twice daily along with statins for one month prior to undergoing PCI might reduce the incidence of periprocedural (type IV) MI by approximately 25% when compared to statins alone (91412).

Age-related macular degeneration (AMD). It is unclear if oral EPA is beneficial for AMD prevention. Details: Population research suggests that increased dietary consumption of EPA does not prevent AMD (10324).
Allergic rhinitis (hay fever). Although there has been interest in using oral EPA for allergic rhinitis, there is insufficient reliable information about the clinical effects of EPA for this condition.
Alzheimer disease. It is unclear if oral EPA is beneficial for Alzheimer disease prevention. Details: Population research suggests that higher dietary intake of EPA is not associated with a decreased risk of developing Alzheimer disease (15041).
Asthma. Although there has been interest in using oral EPA for asthma, there is insufficient reliable information about the clinical effects of EPA for this condition.
Atopic dermatitis (eczema). Although there has been interest in using oral EPA for atopic dermatitis, there is insufficient reliable information about the clinical effects of EPA for this condition.
Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral EPA is beneficial for ADHD treatment or prevention. Details: Some research shows that low plasma levels of EPA and other fatty acids are associated with ADHD in children (15496); however, it is not known if taking EPA supplements can treat or prevent ADHD.
Behcet disease. Although there has been interest in using oral EPA for Behcet disease, there is insufficient reliable information about the clinical effects of EPA for this condition.
Bipolar disorder. Oral fish oil in doses providing 1-2 grams EPA may be beneficial for symptoms of depression in patients with bipolar disorder. It is unclear if EPA alone is beneficial. Details: Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that omega-3 fatty acids in doses standardized to 1-2 grams EPA are weakly recommended for adjunctive use in bipolar depression (110318). This recommendation is based mainly on an early meta-analysis of clinical research of various omega-3 sources (66126). Three clinical trials in this meta-analysis examined the effect of EPA alone in patients with bipolar disorder (110366,110367,110368), with only one study in patients also using stable routine treatment examining the effect of ethyl-EPA 1 gram or 2 grams daily for 12 weeks showing benefit on symptoms of depression, but not mania (110366). The largest clinical trial in patients with bipolar disorder shows that taking ethyl-EPA 6 grams daily for 4 months does not improve symptoms of depression or mania (110368). These findings suggest an unclear effect of ethyl-EPA on symptoms of depression, with no evidence of support for improving symptoms of mania. Also, theoretically, fish oil, a source of EPA in some clinical trials, might increase symptoms of mania in patients with bipolar disorder. Cases of hypomania have been reported in patients with bipolar disorder using fish oil (5713,7202).
Borderline personality disorder. It is unclear if oral EPA is beneficial for improving symptoms of borderline personality disorder. Details: A small clinical trial shows that taking ethyl-EPA 1 gram orally daily for 8 weeks modestly improves aggressive behavior and depression in patients with moderately severe borderline personality disorder when compared with placebo (10348).
Cachexia. It is unclear if oral EPA is beneficial for maintaining lean body mass in patients undergoing chemotherapy. Details: In patients with advanced non-small cell lung cancer, taking an oral nutritional supplement containing EPA (ProSure, Abbott Nutrition) 2 grams daily while undergoing chemotherapy modestly increases lean body mass by 1.6 kg, on average, compared with a 2 kg LOSS of lean body mass with an isocaloric nutritional supplement (91413). In patients with head and neck cancer, starting EPA 2 grams daily along with a polymeric diet prior to chemotherapy and continuing for 6 weeks results in weight and lean body mass maintenance when compared with baseline. However, this maintenance did not differ statistically from losses of 2.1 kg and 1.3 kg, respectively, in patients using the polymeric diet without EPA (99135). A meta-analysis of eight studies in cancer patients shows that taking EPA, usually alone in doses of 1.5-2.2 grams daily for 4-6 weeks, does not seem to prevent loss of lean body mass when compared with placebo. However, it is unclear how many of the included patients had malnutrition and/or weight loss (106070). Also, this analysis included two studies in which EPA was combined with docosahexaenoic acid (DHA) in fish oil.
Chemotherapy-induced diarrhea. It is unclear if oral EPA is beneficial for preventing diarrhea during treatment with chemotherapy. Details: In patients with advanced non-small cell lung cancer, taking an oral nutritional supplement containing EPA (ProSure, Abbott Nutrition) 2 grams daily while undergoing chemotherapy with paclitaxel and cisplatin/carboplatin does not seem to prevent diarrhea when compared with taking an isocaloric control nutritional supplement (91413).
Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral EPA is beneficial for preventing nausea and vomiting during treatment with chemotherapy. Details: In patients with advanced non-small cell lung cancer, taking an oral nutritional supplement containing EPA (ProSure, Abbott Nutrition) 2 grams daily while undergoing chemotherapy with paclitaxel and cisplatin/carboplatin does not seem to prevent nausea or vomiting when compared with taking an isocaloric control nutritional supplement (91413).
Chemotherapy-induced peripheral neuropathy. It is unclear if oral EPA is beneficial for preventing peripheral neuropathy during treatment with chemotherapy. Details: In patients with advanced non-small cell lung cancer, taking an oral nutritional supplement containing EPA (ProSure, Abbott Nutrition) 2 grams daily while undergoing chemotherapy with paclitaxel and cisplatin/carboplatin moderately prevents the development of neuropathy symptoms when compared with taking an isocaloric control nutritional supplement (91413).
Chemotherapy-related fatigue. It is unclear if oral EPA is beneficial for preventing fatigue during treatment with chemotherapy. Details: In patients with advanced non-small cell lung cancer, taking an oral nutritional supplement containing EPA (ProSure, Abbott Nutrition) 2 grams daily while undergoing chemotherapy with paclitaxel and cisplatin/carboplatin modestly reduces symptoms of fatigue when compared with taking an isocaloric control nutritional supplement (91413).
Cognitive function. It is unclear if oral EPA alone is beneficial for improving cognitive function. Details: Clinical research in young and middle-aged adults shows that taking an omega-3 supplement providing EPA 900 mg plus docosahexaenoic acid (DHA) 360 mg (Accelon EPA EE, BASF) daily for 6 months improves some measures of cognitive function, including overall speed and overall memory-related accuracy, when compared with both placebo or an omega-3 supplement providing DHA 900 mg and EPA 270 mg daily (Accelon DHA EE, BASF). There were no benefits on other measures of cognitive performance (109215).
Colorectal adenoma. Taking oral EPA with aspirin might reduce the development of new colorectal adenomas. However, it is unclear if oral EPA alone is beneficial. Details: Clinical research in adults determined to be at high risk for colorectal cancer shows that taking EPA 2 grams, with or without aspirin 300 mg, daily for one year does not reduce the rate of adenoma detection during colonoscopy when compared with placebo or aspirin alone. However, the combination of EPA with aspirin seems to reduce the total number of detected adenomas when compared with taking either EPA or aspirin alone (102501).
Coronary heart disease (CHD). It is unclear if oral EPA alone is beneficial for CHD. Details: Population research suggests that increased dietary consumption of EPA is associated with a modest decrease in the risk of mortality in patients with CHD (10322). Also, preliminary clinical research shows that patients with hypercholesterolemia and a history of CHD who take ethyl-EPA 600 mg three times daily have a 19% reduction in the risk of major coronary events; however, ethyl-EPA doesn't appear to reduce sudden cardiac death (15497).
Cystic fibrosis. Although there has been interest in using oral EPA for cystic fibrosis, there is insufficient reliable information about the clinical effects of EPA for this condition.
Diabetes. It is unclear if oral EPA is beneficial for glycemic control. Details: A small study shows that taking EPA 4 grams daily for 6 weeks does not seem to substantially improve cholesterol, blood sugar, or glycated hemoglobin in patients with type 2 diabetes when compared with placebo. However, triglyceride levels are reduced (10321).
Dysmenorrhea. Although there has been interest in using oral EPA for dysmenorrhea, there is insufficient reliable information about the clinical effects of EPA for this condition.
Exercise-induced muscle damage. It is unclear if oral EPA alone is beneficial for preventing exercise-induced muscle damage. Details: Small clinical studies in untrained healthy males show that taking fish oil providing EPA 600 mg and docosahexaenoic acid (DHA) 260 mg daily for 4-8 weeks prior to exhaustive unaccustomed exercise has beneficial effects on immediate and/or delayed muscle soreness and range of motion when compared with placebo (98257,109222).
Fractures. Oral EPA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study shows that taking omega-3 fatty acids 1 gram daily, providing EPA 330 mg and docosahexaenoic acid (DHA) 660 mg, for 3 years does not prevent fractures in adults over 70 years of age when compared with placebo. These findings were consistent in adults taking omega-3 fatty acids alone or combined with vitamin D 2000 IU daily and/or strength training three times weekly (104619).
Huntington disease. It is unclear if oral EPA is beneficial for this condition. Details: A meta-analysis of five clinical studies in adults with Huntington disease shows that taking EPA 1-2 grams daily for 6 months does not improve motor scores or symptoms when compared with placebo. In two clinical studies that continued for an additional 6 months, EPA supplementation improved total motor score at 12 months. However, the validity of this finding is confounded because the largest clinical trial included in this analysis converted to an open-label design after the first 6 months, eliminating the placebo control and introducing the risk for patient and investigator bias (102505).
Hypercholesterolemia. It is unclear if oral EPA is beneficial for improving lipid levels. Details: Small clinical trials shows that taking EPA alone reduces serum triglyceride concentrations, but has no effect on total and low-density lipoprotein (LDL) cholesterol in mildly hypercholesterolemic males (6143,10322). The effect of EPA on cholesterol levels in other populations has also been evaluated. In patients with type 2 diabetes, EPA can increase high-density lipoprotein (HDL) cholesterol levels by approximately 12% (10321). In normolipidemic individuals, an algal oil enriched in EPA reduced levels of very low-density lipoprotein (VLDL) and total cholesterol but had no effect on triglyceride or LDL cholesterol levels (103314). Also, a meta-analysis of clinical research shows that taking EPA modestly decreases total and LDL cholesterol levels when compared with placebo (109216). However, not all patients in these studies had hyperlipidemia, and EPA was usually provided in oils that also include docosahexaenoic acid.
Hypertension. Small clinical studies suggest that oral EPA, when used alone or in combination with docosahexaenoic acid (DHA), does not lower blood pressure. Details: A meta-analysis of clinical research in adults with dyslipidemia shows that supplemental EPA reduces systolic, but not diastolic, blood pressure when compared with control (102389). Other preliminary clinical research in adults with slightly elevated diastolic blood pressure (84-94 mmHg) also shows that taking a combination of EPA 0.48 grams plus gamma-linolenic acid 0.12 grams does not reduce diastolic blood pressure (13771). A large clinical study shows that taking omega-3 fatty acids 1 gram daily, providing EPA 330 mg and DHA 660 mg, for 3 years does not reduce blood pressure levels in adults over 70 years of age when compared with placebo. These findings were consistent in adults taking omega-3 fatty acids alone or combined with vitamin D 2000 IU daily and/or strength training three times weekly. About 39% of the individuals included in this study were diagnosed with hypertension and about 50% were using antihypertensives (104619).
IgA nephropathy. Although there has been interest in using oral EPA for IgA nephropathy, there is insufficient reliable information about the clinical effects of EPA for this condition.
Intrauterine growth restriction (IUGR). It is unclear if oral EPA during pregnancy reduces the risk of IUGR. Details: A small clinical study in patients with a history of IUGR during a previous pregnancy shows that taking EPA 3 grams daily, starting at 12-14 weeks gestation and continuing until delivery, does not seem to reduce the risk of IUGR when compared with placebo (1027).
Lung cancer. It is unclear if oral EPA is beneficial for lung cancer treatment. Details: In patients with advanced non-small cell lung cancer, taking an oral nutritional supplement containing EPA (ProSure, Abbott Nutrition) 2 grams daily while undergoing chemotherapy with paclitaxel and cisplatin/carboplatin does not improve tumor response rate, survival, or physical functioning over a 12 month period when compared with taking an isocaloric control nutritional supplement (91413).
Menopausal symptoms. It is unclear if oral EPA reduces hot flashes after menopause. Details: In post-menopausal adults with mild hot flash symptoms, clinical research shows that taking ethyl-EPA (ethyl-EPA) 500 mg three times daily, provides modest reduction in the frequency of hot flashes when compared with placebo. After 8 weeks of treatment, the mean number of hot flashes decreased by 1.58 per day in those taking ethyl-EPA. However, taking ethyl-EPA did not significantly decrease the severity of hot flashes or improve overall quality of life (16901). Research in patients with more severe hot flash symptoms is needed to confirm these results.
Metabolic syndrome. Although there has been interest in using oral EPA for metabolic syndrome, there is insufficient reliable information about the clinical effects of EPA for this condition.
Migraine headache. Although there has been interest in using oral EPA for migraine headache, there is insufficient reliable information about the clinical effects of EPA for this condition.
Muscle strength. It is unclear if oral EPA is beneficial for increasing muscle strength. Details: A large clinical study shows that taking omega-3 fatty acids 1 gram daily, providing EPA 330 mg and docosahexaenoic acid (DHA) 660 mg, for 3 years does not increase muscle strength in adults over 70 years of age when compared with placebo. These findings were consistent in adults taking omega-3 fatty acids alone or combined with vitamin D 2000 IU daily and/or strength training three times weekly (104619).
Physical performance. Taking EPA does not seem to improve physical performance in patients requiring mechanical ventilation. It is unclear if oral EPA is beneficial for increasing physical performance in older adults. Details: Clinical research in mechanically ventilated patients shows that taking EPA 2 grams daily for 10 days, alone or with beta-hydroxymethylbutyrate 3 grams daily, does not increase diaphragm or quadriceps strength or thickness when compared with placebo (109223). Also, a large clinical study shows that taking omega-3 fatty acids 1 gram daily, providing EPA 330 mg and docosahexaenoic acid (DHA) 660 mg, for 3 years does not improve physical performance in adults over 70 years of age when compared with placebo. These findings were consistent in adults taking omega-3 fatty acids alone or combined with vitamin D 2000 IU daily and/or strength training three times weekly (104619).
Postoperative infection. Oral EPA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that enteral nutrition supplemented with EPA in combination with RNA and L-arginine, given during the postoperative period, reduces the percentage of patients experiencing postoperative infectious/wound complications and shortens the duration of hospitalization by about 4 days when compared to standard enteral nutrition (5531). It is not clear if this effect is due to EPA, RNA, L-arginine, or the combination.
Postoperative recovery. It is unclear if oral EPA helps to maintain postoperative lean body mass. Details: Weight loss and malnutrition are common after esophageal cancer resection. Preliminary clinical research shows that administering EPA-enhanced enteral nutrition does not attenuate loss of body weight or lean body mass by one month post-esophagectomy when compared with standard enteral nutrition (96504).
Pregnancy-induced hypertension. It is unclear if oral EPA during pregnancy reduces the risk of hypertension. Details: A small study in patients with a history of intrauterine growth restriction during a previous pregnancy shows that taking EPA 3 grams daily, starting at 12-14 weeks gestation and continuing until delivery, does not seem to reduce the risk of pregnancy-induced hypertension when compared with placebo (1027).
Prostate cancer. It is unclear if oral EPA is beneficial for prostate cancer treatment or prevention. Details: Preliminary clinical research shows that taking EPA 4.48 grams and docosahexaenoic acid 2.88 grams daily for 12 weeks reduces prostate specific antigen (PSA) levels in men with normal PSA levels at baseline. However, it is unclear if this effect was due to EPA alone. Additionally, it is unclear if this leads to a reduced risk for prostate cancer (89423). Observational research regarding the association between EPA and prostate cancer risk is conflicting. Although some early research suggests a possible association, a meta-analysis including this and other prospective observational research shows that increased dietary intake or serum levels of EPA are not associated with overall prostate cancer risk (90677,102503). One observational study in men with existing low-risk prostate cancer shows that the highest tertile of prostate tissue levels of EPA, as well as the highest tertile of dietary intake, is associated with 71% to 75% reduced odds for progression to high-grade prostate cancer when compared with the lowest tertile (102502). However, other prospective observational research suggests that increased dietary intake of EPA may be associated with an increased risk for fatal prostate cancer (102503). High-quality prospective research is needed to clarify these findings.
Psoriasis. It is unclear if oral EPA is beneficial in psoriasis. Details: Preliminary clinical research shows that taking ethyl-EPA 1.8 grams daily in combination with low-dose (20 mg per day) etretinate (Tegison, no longer available in the US) for 12 weeks is more effective than etretinate alone for plaque psoriasis (66478).
Quality of life. It is unclear if oral EPA is beneficial for improving quality of life in patients with cancer. Details: A meta-analysis of eight clinical trials in cancer patients shows that taking EPA, usually alone in doses of 2-2.2 grams daily for 6-12 weeks, does not seem to improve quality of life when compared with placebo (106070). This analysis included two studies in which EPA was combined with docosahexaenoic acid (DHA) in fish oil.
Schizophrenia. Evidence for the use of oral EPA in schizophrenia is conflicting. Details: Some clinical research shows that EPA improves mental state and reduces dyskinesia when taken along with antipsychotic medications (8720). However, other clinical research shows that EPA does not improve mental state, cognitive function, or mood in patients with schizophrenia who are taking antipsychotics (10347). A meta-analysis of clinical research shows that EPA modestly improves the mental state of patients with schizophrenia who are not taking antipsychotic medications prior to treatment, but not those already being treating with antipsychotics at baseline. Some evidence suggests that ethyl-EPA might be more effective than EPA. Taking EPA does not appear to significantly decrease the need for conventional antipsychotics (15039). EPA or ethyl-EPA 1-3 grams daily in divided doses for 12-16 weeks has been used in these studies (8720,15039).
Systemic lupus erythematosus (SLE). Although there has been interest in using oral EPA for SLE, there is insufficient reliable information about the clinical effects of EPA for this condition.
Systemic lupus erythematosus (SLE) nephritis. Although there has been interest in using oral EPA for SLE nephritis, there is insufficient reliable information about the clinical effects of EPA for this condition.
Ulcerative colitis. It is unclear if oral EPA is beneficial for ulcerative colitis prevention and treatment. Details: Population research derived from the Nurses' Health Study shows that a higher dietary intake of omega-3 fatty acids is associated with a reduced incidence of ulcerative colitis. One study shows that taking EPA 1 gram twice daily for 6 months reduces fecal calprotectin levels, a marker of intestinal mucosal inflammation, by 40% when compared with placebo. Additionally, a 27% reduction in disease relapse was seen in the EPA group (96503).
Wound healing. Although there has been interest in using oral EPA for wound healing, there is insufficient reliable information about the clinical effects of EPA for this condition. More evidence is needed to rate eicosapentaenoic acid for these uses.

HUPERZINE A

Alzheimer disease. Oral huperzine A seems to improve memory, cognitive function, and behavior in patients with this condition. Details: Meta-analyses of small clinical studies in patients with Alzheimer disease show that, overall, huperzine A 200-800 mcg in 2-3 divided doses daily for 8-36 weeks improves cognitive function as measured on some scales, but not others, when compared with placebo (55674,93482). Improvement in cognitive function was observed consistently when measured using the Mini-Mental State Examination (MMSE) (55674,93482,93483,101469). However, results are inconsistent with other scales, such as the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Hasegawa Dementia Scale (HDS), and the Wechsler Memory Scale (WMS) (55674,93482). Meta-analyses also show that huperzine A improves overall behavior and performance of daily living activities when compared with placebo (55674,93482). Most research has been conducted in China, where huperzine A is an approved drug for this condition. Only one clinical trial has been conducted in the United States. This study was conducted in patients with probable mild to moderate Alzheimer disease and shows that taking huperzine A 200 mcg twice daily for at least 16 weeks does not improve cognition based on the ADAS-Cog when compared with placebo. However, this dose results in modest benefit when cognition is measured using the MMSE, and a higher dose of 400 mcg twice daily shows modest benefit when measured on both the ADAS-Cog and MMSE (93479). Long-term, large-scale clinical trials in diverse geographic locations are necessary to confirm these findings and determine which dose of huperzine A, if any, is beneficial.

Athletic performance. It is unclear if oral huperzine A is beneficial for improving athletic performance. Details: One very small, double-blind randomized crossover study in physically active adults shows that taking huperzine A 200 mcg as a single dose 30-45 minutes prior to exercise does not affect athletic performance, neuromuscular performance, or cognitive function when compared with placebo (107470). Due to the single-dose nature of this study, the effects of continued administration of huperzine A on athletic performance are unclear.
Cocaine dependence. It is unclear if oral huperzine A is beneficial in patients with cocaine use disorder. Details: A very small clinical study in adults with cocaine use disorder shows that taking huperzine A in gradually increasing doses over 9 days, up to a dose of 200 or 400 mcg twice daily, might attenuate the stimulation and anxiety effects of an intravenous cocaine infusion when compared with placebo (93484). It is unclear if huperzine A can attenuate cravings and cocaine use in these individuals.
Cognitive impairment. Although there is interest in using oral huperzine A for mild cognitive impairment, there is insufficient reliable information about the clinical effects of huperzine A for this condition.
Depression. It is unclear if oral huperzine A is beneficial in patients with major depressive disorder. Details: A meta-analysis of three small, low-quality clinical studies in patients with major depressive disorder shows that taking huperzine A 100-300 mg daily in combination with antidepressants for 6-8 weeks does not further improve depressive symptoms when compared with antidepressants alone. However, huperzine A might improve cognitive functioning, based on the Wisconsin Card Sorting Test and the Wechsler Memory Scale-Revised (WMS-R) (93485). All available research has been conducted in China, so it is unclear if these findings are generalizable to other geographic locations.
Memory. It is unclear if oral huperzine A is beneficial for improving memory in healthy adolescents. Details: A small clinical trial in Chinese adolescents around 15 years of age who complain of poor memory shows that taking huperzine A 100 mcg daily for 4 weeks improves memory quotient scores when compared with placebo (4626).
Myasthenia gravis. It is unclear if intramuscular huperzine A is beneficial in patients with myasthenia gravis. Details: A small, open-label clinical trial in stabilized patients with myasthenia gravis shows that giving huperzine A 400 mcg intramuscularly for 10 days maintains muscle strength similarly to patients treated with intramuscular neostigmine alternating with intramuscular huperzine A. Huperzine A was reported to have a 7-hour duration of effect, compared to only 4 hours with neostigmine (3561).
Schizophrenia. Small clinical studies suggest that oral huperzine A may modestly improve symptoms of schizophrenia in adults. Details: A meta-analysis of small, low-quality clinical trials in hospitalized patients with schizophrenia shows that taking huperzine A 150-400 mcg daily for 8-24 weeks as an adjunct to antipsychotic medications improves memory, intelligence, and positive, but not negative, psychiatric symptoms when compared with antipsychotic medications alone (93478). Limited research also suggests that huperzine A might improve outcomes in patients with resistant schizophrenia and cognitive impairment. A small, open-label clinical study in patients with treatment-resistant schizophrenia and cognitive impairment shows that adding huperzine A 300 mcg daily for 12 weeks to treatment with antipsychotics improves negative symptoms of schizophrenia by 32% and memory by 15% when compared to baseline (55665). The validity of this finding is limited by the lack of a comparator group. Furthermore, all available research has been conducted in China, so it is unclear if these findings are generalizable to other geographic locations.
Vascular dementia. Small clinical studies suggest that oral huperzine A may modestly improve symptoms of vascular dementia in adults. Details: A meta-analysis of two small clinical trials in patients with vascular dementia shows that taking huperzine A 200-300 mcg daily for 12-24 weeks modestly improves cognitive function and activities of daily living when compared with control (93483). The validity of this meta-analysis is limited by small study size and publication bias. More evidence is needed to rate huperzine A for these uses.

Ulcerative colitis. Limited clinical research shows that taking phosphatidylcholine products may improve clinical and remission scores in adults with ulcerative colitis. Details: Clinical research suggests that taking slow-release, phosphatidylcholine-rich phospholipids (Sterpur P-30 Granulat, Stern-Lecithin and Soja GmbH) improves symptoms and remission rate in patients with ulcerative colitis (68839,93389,93390,105728). A pooled analysis of 3 small randomized clinical trials in adults with chronic, active, ulcerative colitis at a single site shows that taking this specific form of phosphatidylcholine 1-4 grams daily for 3 months increases the odds of achieving clinical remission by 9.7 times when compared with placebo. Overall, 49% of the patients taking phosphatidylcholine achieved clinical remission. Taking phosphatidylcholine also improved quality of life and clinical improvement scores. In one study, this product also decreased the need for steroids, resulting in complete withdrawal of steroid therapy without exacerbation of disease in 80% of patients (93390). However, most patients in these studies were not treated with other standard therapies for ulcerative colitis, such as immunosuppressants and aminosalicylic acids. Subgroup analyses by dose suggest that the effective dose of this product is at least 1 gram daily; however, taking 3-4 grams daily may be more effective (93389,105728). In patients not responsive to mesalamine, some preliminary clinical research suggests taking LT-02 (Lipid Therapeutics GmbH), a modified-release formula of phosphatidylcholine, 3.2 grams daily for 12 weeks, improves symptoms of ulcerative colitis. Overall disease activity was improved by 52%, compared with 33% in those taking placebo. The effects on remission rate and mucosal healing were unclear; however, response rates were increased from 60% in the placebo group to 83% in the phosphatidylcholine group. In an 8-week follow-up, relapse was also less likely in patients treated with this product (93387).

Acne. Topical phosphatidylcholine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a topical cream containing niacinamide and linoleic acid-rich phosphatidylcholine (4% niacinamide-phospholipidic; N-PHCL emulsion) once daily for 12 weeks improves skin hydration and reduce acne lesions and inflammation when compared with a 1% clindamycin cream or a carrier-only cream in patients 15 years and older with moderate acne (93388).
Aging. Although there has been interest in using oral phosphatidylcholine for aging, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Alcohol-related liver disease. It is unclear if oral phosphatidylcholine is beneficial in patients with alcohol-related liver disease. Details: Preliminary clinical research in adults with acute alcoholic hepatitis shows that taking polyunsaturated phosphatidylcholine 6 grams orally daily for 24 months does not increase survival when compared with placebo (68843).
Alzheimer disease. Although there has been interest in using oral phosphatidylcholine for Alzheimer disease, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Angina. Although there has been interest in using intravenous phosphatidylcholine for angina, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Anxiety. Although there has been interest in using oral phosphatidylcholine for anxiety, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Atherosclerosis. Although there has been interest in using intravenous phosphatidylcholine for atherosclerosis, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Atopic dermatitis (eczema). Although there has been interest in using oral phosphatidylcholine for atopic dermatitis, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Bipolar disorder. Although there has been interest in using oral phosphatidylcholine for bipolar disorder, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Dementia. It is unclear if oral phosphatidylcholine is beneficial in patients with dementia. Details: Population research in a sample of 1259 men in Finland suggests that high daily intake of phosphatidylcholine is associated with a 28% lower risk of developing dementia when compared with low daily intake, over a mean follow-up of about 22 years (103178).
Fatty deposits. It is unclear if subcutaneous phosphatidylcholine is beneficial in patients with fatty deposits. Details: Very low quality clinical research shows that administering subcutaneous injections of phosphatidylcholine 125 mg-250 mg every 7-15 days can reduce localized fatty deposits on the chin, thigh, hips, abdomen, back, neck, and elsewhere, based on subjective visual assessments, when compared with baseline (15621,15625,15627). Improvements appear to last for 2-3 years or longer (15621,15627). In one study, phosphatidylcholine injections markedly or moderately reduce localized fatty deposits on the face in about 80% of patients for a period of up to 3 years based on subjective patient self-assessment (15621).
Hepatic encephalopathy. It is unclear if oral phosphatidylcholine is beneficial in patients with hepatic encephalopathy. Details: Preliminary clinical research shows that taking polyunsaturated phosphatidylcholine 1050 mg daily for 6-8 weeks, either orally or through a nasogastric tube, does not improve recovery from encephalopathy compared with control in patients with acute or subacute liver failure. However, polyunsaturated phosphatidylcholine seems to reduce mortality compared to control in patients with subacute, but not acute, liver failure (68835).
Hepatitis A. It is unclear if oral phosphatidylcholine is beneficial in patients with hepatitis A. Details: Preliminary clinical research shows that taking phosphatidylcholine 900 mg orally daily for 12 weeks does not seem to reduce serum bilirubin or liver enzyme levels in patients with hepatitis A when compared with no intervention (5225).
Hepatitis B. It is unclear if oral phosphatidylcholine is beneficial in patients with hepatitis B. Details: Preliminary clinical research in adults undergoing interferon treatment for hepatitis B shows that taking phosphatidylcholine 1.8 grams orally daily for 24 weeks improves clinical response when compared with placebo (5226). Other preliminary clinical research in patients with chronic active hepatitis B shows that taking phosphatidylcholine 3 grams orally improves histological disease scores when compared with control (5224).
Hepatitis C. Oral phosphatidylcholine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults undergoing interferon treatment for hepatitis C shows that taking phosphatidylcholine 1.8 grams orally daily for 24 weeks improves clinical response when compared with placebo (5226).
Hypercholesterolemia. Although there has been interest in using intravenous phosphatidylcholine for hypercholesterolemia, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Hyperlipidemia. Although there has been interest in using oral phosphatidylcholine for hyperlipidemia, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Hyperlipoproteinemia. Oral phosphatidylcholine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking polyunsaturated phosphatidylcholine 1.8 grams daily for 28 days in combination with clofibrate does not significantly reduce total cholesterol, triglycerides, or phospholipids compared to clofibrate alone in patients with primary hyperlipoproteinemia of Fredrickson Types II or IV. However, taking the combination of polyunsaturated phosphatidylcholine plus clofibrate seems to significantly attenuate the relative increase in low-density lipoprotein (LDL) cholesterol when compared with clofibrate alone (68840).
Infant development. It is unclear if oral phosphatidylcholine is beneficial for infant development. Details: Preliminary clinical research shows that taking phosphatidylcholine (PhosChol, Nutrasal) 5 grams daily, containing choline 750 mg daily, from 18 weeks' gestation to 90 days postpartum does not improve cognitive function in the infant at 10-12 months of age when compared with corn oil placebo (93386).
Lipoma. It is unclear if subcutaneous phosphatidylcholine is beneficial in patients with lipoma. Details: An anecdotal report suggests that injecting a phosphatidylcholine solution directly into a lipoma can shrink the tumor by about 35%. However, in this report a major inflammatory reaction occurred, resulting in undesirable fibrotic changes to the tissue and eventual surgical excision of the lipoma (15622).
Memory. It is unclear if oral phosphatidylcholine is beneficial for memory. Details: Preliminary clinical research shows that taking a single dose of phosphatidylcholine 25 grams (PC-55, TwinLab) orally can improve some measures of memory in healthy college students when compared with placebo (5228).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral phosphatidylcholine is beneficial in patients with NAFLD. Details: Preliminary clinical research shows that taking phosphatidylcholine 600 mg orally three times daily for 24 weeks qualitatively improves liver echogenicity and structure on an ultrasound scan, suggesting a reduction in hepatic steatosis, when compared to baseline. There is also a small decrease in liver function test values, but with considerable variability both at baseline and at 24 weeks (103176,103177). Preliminary clinical evidence also suggests that taking a combination of the milk thistle constituent silybin, phosphatidylcholine, and vitamin E (Realsil, Instituto Biochimico Italiano) orally twice daily for 12 months improves liver function tests (LFTs) and liver histology when compared with placebo in people with NAFLD (63244). It is unclear if this effect is due to phosphatidylcholine, other ingredients, or the combination.
Periorbital fat pad herniation. It is unclear if subcutaneous phosphatidylcholine is beneficial in patients with periorbital fat pad herniation. Details: Preliminary clinical research shows that injecting phosphatidylcholine 20 mg subcutaneously every 2 weeks markedly reduces lower eyelid fat pads in people with bulging fat pads due to herniation when compared to baseline. In some people, benefits appeared to last for a period of 9 months to 2 years or longer (15623,15628).
Peripheral arterial disease (PAD). Although there has been interest in using oral phosphatidylcholine for PAD, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Peritoneal dialysis. It is unclear if oral phosphatidylcholine is beneficial in patients with peritoneal dialysis. Details: Very preliminary clinical research shows that taking phosphatidylcholine 900 mg orally daily for 8 weeks does not improve ultrafiltration in peritoneal dialysis when compared to baseline (5222).
Premenstrual syndrome (PMS). Although there has been interest in using oral phosphatidylcholine for PMS, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
Tardive dyskinesia. It is unclear if oral phosphatidylcholine is beneficial in patients with tardive dyskinesia. Details: Preliminary clinical research taking phosphatidylcholine 30 grams orally daily for 6 weeks does not improve tardive dyskinesia symptoms when compared with placebo (5223). More evidence is needed to rate phosphatidylcholine for these uses.

Allergic rhinitis (hay fever). Oral turmeric seems to improve symptoms in people with allergic rhinitis. Details: A large clinical study in people with allergic rhinitis shows that taking a specific curcumin product (Organika Health Products) 500 mg daily for 2 months reduces nasal symptoms, including sneezing, itching, runny nose, and congestion, when compared with placebo (96138).
Depression. Most research shows that oral curcumin, a constituent of turmeric, 1 gram daily improves symptoms of depression after 6 weeks when taken along with an antidepressant. However, it is unclear whether curcumin is beneficial when used for greater than 8 weeks. Details: Curcumin appears to be most beneficial for depression in middle aged patients compared to older patients, when taken for at least 6 weeks, and when used at a dose of at least 1 gram daily. In adults with major depressive disorder, a meta-analysis of data from six clinical studies, as well as individual studies not included in this analysis, show that taking curcumin 1 gram daily along with an antidepressant moderately improves depression symptoms when compared with placebo (96131,96139). Another meta-analysis of 10 studies shows symptom reductions in patients with major depression when combined with conventional antidepressants, but not when used alone in patients with milder depressive symptoms. However, the quality of the evidence is low (104971). When used alone, one clinical study shows that curcumin 1 gram daily for 6 weeks may be similarly effective to fluoxetine 20 mg daily. Taking both products together seems to be more effective than either product alone, increasing the response rate from 65% to 78% (89728). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that curcumin extract at doses of 500-1000 mg daily is provisionally recommended for monotherapy or adjunctive use in mild to moderate depression (110318).
Dyspepsia. Oral turmeric may be modestly beneficial for some patients with dyspepsia. In patients with functional dyspepsia, small clinical studies show that oral curcumin, a constituent of turmeric, is similarly effective when compared with the proton-pump inhibitor omeprazole. Details: Clinical research shows that taking turmeric 500 mg four times daily for 7 days can relieve overall symptoms of dyspepsia in 64% more patients than taking placebo (11144). A small, unblinded clinical study in patients with a type of dyspepsia called postprandial distress syndrome shows that taking turmeric 250 mg or 500 mg orally three times daily after meals for 4 weeks is associated with reductions in symptom scores which are similar to those seen with simethicone 60 mg three times daily for 4 weeks. However, the recurrence rate upon stopping therapy was about 14% with simethicone, compared with 43% to 46% with turmeric (104963). In patients with functional dyspepsia, taking the constituent curcumin appears similarly effective when compared with omeprazole, but might not provide further symptom reduction in those also taking famotidine or omeprazole (106063,106801,111599). One small clinical study in Iran shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing overall symptoms of dyspepsia, such as abdominal pain, heartburn, bloating, and nausea, when compared with famotidine alone (106063). Another small clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity and improving satisfaction when compared with an unspecified dose of omeprazole and more effective when compared with placebo (106801). Similarly, a moderate-size clinical study in Thailand shows that taking curcumin 500 mg four times daily for 4 weeks is similarly effective for reducing dyspepsia severity when compared with omeprazole 20 mg daily. However, taking curcumin and omeprazole in combination did not provide further symptom reduction (111599). The validity of these results is limited by the high rate of study dropouts.
Hyperlipidemia. Research is conflicting on whether oral turmeric, curcumin, or curcuminoids can reduce serum lipids. Any improvement in lipids is likely to be small. Reasons for the conflicting findings may relate to turmeric formulation, duration of treatment, and/or the baseline cholesterol status of the included patients. Details: Results from meta-analyses of clinical research show inconsistent and conflicting results. One large meta-analysis of over 50 clinical studies in healthy adults and those with a variety of conditions shows that supplementation with turmeric or curcumin 80-4000 mg daily for 4-24 weeks reduces total cholesterol by 4 mg/dL, low-density lipoprotein (LDL) cholesterol by 5 mg/dL, and triglycerides by 7 mg/dL and increases high-density lipoprotein (HDL) cholesterol by 2 mg/dL when compared with placebo (112119). Two other meta-analyses of 27 clinical studies agree that taking turmeric, curcumin, or curcuminoids moderately reduce triglyceride levels but suggest that turmeric does not improve total cholesterol when compared with placebo. However, the meta-analyses contradict one another on whether turmeric and its constituents reduce LDL cholesterol or increase HDL cholesterol. (96128,96135). Additionally, a third meta-analysis of 10 clinical trials shows that taking up to 2400 mg daily of curcumin or curcuminoids, from turmeric or isolated sources, for up to 12 weeks, does not significantly improve triglycerides, LDL cholesterol, HDL cholesterol, or total cholesterol (110220).
Nonalcoholic fatty liver disease (NAFLD). Oral curcumin, a constituent of turmeric, seems to attenuate fat deposition and improve some metabolic parameters in adults with NAFLD. Details: Clinical research shows that taking curcumin daily reduces NAFLD severity in 30% to 79% of patients, compared to 5% to 27.5% of patients receiving placebo. Curcumin also reduces the quantity of additional fat deposition in the liver to 0% to 4.5%, compared to 17.5% to 26% in those taking placebo. Most research shows that taking curcumin also reduces liver enzyme levels, body mass index (BMI), blood glucose levels, glycated hemoglobin (HbA1c), and total cholesterol when compared with placebo. Although some clinical research shows that taking curcumin improves levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, a meta-analysis of clinical research shows that these lipid levels are not improved in patients with NAFLD, specifically (97430,97431,100258,102350,106062,107120,109279,111349). However, another meta-analysis of 14 small, heterogeneous clinical studies in adults with NAFLD, that included some of these studies, shows that taking various doses and forms of turmeric or curcumin modestly reduces liver enzyme levels, improves measures of insulin resistance, reduces waist circumference, and improves LDL, HDL, and triglyceride levels when compared with placebo (111348). A small clinical trial in patients with NAFLD given specific lifestyle recommendations shows that taking curcumin modestly reduces the frequency of metabolic syndrome and fatty liver but does not have beneficial effects on fatty liver-associated indices, adiposity, or the atherogenic index, when compared with placebo (109285). Findings for specific endpoints are mixed between individual studies and may depend on the formulation of curcumin used or the duration of treatment. These studies have used various doses and formulations. In one study, 500 mg of a dispersion formulation equivalent to 70 mg of curcumin daily for 8 weeks was used (97430). Also, 250 mg once daily or 500 mg twice daily of a specific phytosomal formulation (Meriva, Indena) containing curcumin and soy phosphatidylcholine in a 1:2 ratio and standardized to an overall curcuminoid content of 20% was taken for 8 weeks (97431,106062). Another study used 1 gram of powdered turmeric rhizome taken three times daily with meals for 12 weeks (102350). One study used a curcumin-piperine complex (Curcumin C3 complex 500 mg plus Bioperine 5 mg) daily for 8 weeks (107120). One study used curcumin (Arjuna Natural Extract) 500 mg three times daily for 12 weeks (109285). Despite positive results with curcumin in several small clinical studies of patients with NAFLD, there is some concern that curcumin might cause hepatotoxicity in rare cases, especially when highly bioavailable formulations are used in high doses (103633). There is also evidence that the risk for hepatotoxicity with curcumin may be increased in individuals with the HLAB*35:01 allele (109288). Curcumin-induced hepatotoxicity has not been reported in clinical trials of patients with NAFLD, and its potential mechanism is unclear. However, patients seeking to take curcumin for NAFLD should be advised to monitor for symptoms of hepatotoxicity, including abdominal pain, dark urine, fatigue, jaundice, nausea, and pruritus.
Oral mucositis. Oral curcumin or curcumin-containing mouthwash seem to reduce the development of severe oral mucositis, as well as reduce the severity and pain of oral mucositis, associated with cancer treatment. Details: Clinical research in patients receiving radiotherapy following recent radical surgery for oral cancer shows that taking turmeric (BCM-95, Arjuna Natural Pvt. Ltd., India) during radiotherapy reduces the incidence of severe oral mucositis to 25% or 20% in those taking turmeric 500 mg two or three times daily, respectively, compared with 65% in those taking placebo. The incidences of severe oral pain, dysphagia, and dermatitis were also reduced by at least 50% (105398). A small clinical study in patients receiving chemotherapy with or without head and neck radiotherapy shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 7 weeks improves severity of oral mucositis at weeks 1, 4, and 7 and reduces pain at week 7 when compared with placebo. Effects were more pronounced in those with chemotherapy-induced oral mucositis than radiotherapy-induced oral mucositis (106800). In patients with head and neck cancer receiving radiotherapy, preliminary clinical research shows that swishing with 10 mL of turmeric solution (prepared by dissolving turmeric 400 mg in 80 mL of water) six times daily for 6 weeks delays mucositis and reduces the number of cases of intolerable mucositis by 49% when compared to swishing with 10 mL of povidone-iodine solution twice daily for 6 weeks (89726). Another small clinical study shows that swishing with 10 mL of nanoparticulate curcumin 0.1% mouthwash three times daily for 6 weeks is associated with a 50% lower risk of developing oral mucositis, and a delay of 2 weeks in the onset of mucositis, when compared with benzydamine 0.15% mouthwash (104969). A small clinical study in patients with mucositis due to head and neck radiotherapy shows that taking curcumin nanoparticles (SinaCurcumin, ExirNanoSina) 40 mg daily or using 10 mL of a curcumin 0.1% mouthwash three times daily for up to 21 days improves scores related to pain, burning, ulceration, and erythema when compared with placebo. Results with either oral or topical curcumin were similar (111350).
Osteoarthritis. Some oral turmeric extracts and combination products containing turmeric seem to improve certain symptoms of knee osteoarthritis. However, it is unclear how turmeric compares to the use of non-steroidal anti-inflammatory drugs (NSAIDs). Details: Several meta-analyses of clinical studies show that turmeric extracts and/or curcuminoid products reduce knee pain and stiffness, improve physical function, and reduce the need for rescue medication when compared with placebo (104970,106792,109280,110222). However, a reduced effect was noted in patients with increasing age or body mass index (104790). The studies evaluated in these meta-analyses are heterogeneous, of low- to moderate-quality, and utilized a variety of products and/or dosing strategies (104970,106792,109280,110222). Small to moderate-sized clinical studies show that specific products (Meriva, Indena; Theracurmin, Theravalues Corp) containing curcumin 90-100 mg twice daily for up to 6 months, or specific turmeric extracts (Turmacin, Natural Remedies Pvt. Ltd.; Curcugen, DolCas Biotech, LLC) 500 mg twice daily for 6-12 weeks, reduce pain and analgesic use and improve functionality when compared with placebo (17953,80988,89721,97424,104148,107118). A specific turmeric extract (CuraMed, EuroPharma USA) 1500 mg daily for 12 weeks improves functionality, but not pain, when compared with placebo (96127). Also, a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 40 mg twice daily for 6 weeks, improves pain, stiffness, and physical activity scores and reduces intake of rescue acetaminophen by about 60% when compared with placebo (102349). However, not all turmeric products seem to be effective for improving symptoms of osteoarthritis. One small clinical study shows that taking a specific turmeric extract (B-Turmactive, PLAMECA S.A.) 500 mg daily for one week does not reduce knee pain when compared with placebo (104147). Also, a meta-analysis of clinical research shows that benefits are limited to bio-optimized forms of curcuminoids, and benefits related to pure extracts are lacking (110222). Turmeric has also been compared with conventional treatments for knee osteoarthritis in small meta-analyses, a network meta-analysis, and individual clinical studies. However, the evidence is mixed as to whether turmeric is as effective or more effective than NSAIDs, such as ibuprofen 400 mg taken 2-3 times daily, diclofenac 25-100 mg daily, or chondroprotective drugs (17952,89720,89722,106792,109280,110222,113607). A network meta-analysis comparing 6 interventions in adults with knee osteoarthritis suggests that curcumin monotherapy, curcumin with chondroprotective agents, or curcumin with NSAIDs improves scores related to pain, function, and stiffness while reducing the need for rescue medication and the incidence of adverse events (113607). Individual studies are heterogenous with respect to comparator medication and dosing schedule. Doses included a non-commercial turmeric extract 500 mg 3-4 times daily for 4-6 weeks (17952,89720) or turmeric extract 500 mg twice daily for 3 months (89722). Topical turmeric has also been evaluated. One clinical study shows that applying curcumin topically as a 5% ointment in Vaseline twice daily for 6 weeks reduces pain associated with knee osteoarthritis by a mean of about 11 on a 100-point visual analog scale when compared with placebo (104964). Another clinical study in patients with knee osteoarthritis shows that applying curcumin in a self-nano-emulsifying polyethylene glycol organogel 1.5 grams to the knee twice daily for 8 weeks reduces pain, stiffness, and difficulty with physical function scores by 72%, 62%, and 46%, respectively, when compared to baseline, with improvements superior to placebo for all outcomes (113357). Research also shows that taking specific combination products containing turmeric and other ingredients can improve pain and functionality in patients with osteoarthritis. These combination products have combined turmeric with chondroitin sulfate and glucosamine hydrochloride (CartiJoint Forte, Fidia Farmaceutici SpA); boswellic acid (Curamin, EuroPharma USA; Rhulief); Boswellia serrata (Rhulief); ashwagandha, Boswellia serrata, and zinc (Articulin-F, Eisen Pharmaceutical Co. Pvt. Ltd.); devil's claw and bromelain (AINAT, Laboratoire de Rhumatologie Appliquée); Boswellia serrata, guggul, and valerian (Phytoproflex, OPTM Healthcare); Boswellia serrata and terminalia (LI73014F2, Laila Nutraceuticals); ashwagandha, Boswellia serrata, and ginger (Artrex, Mendar); or extracts of ginger rhizome, devil's claw tuber, Boswellia serrata resin, and celery seed (Tregocel, Max Biocare) (19276,51950,81466,89717,89719,96127,97419,97421,97428,106078)(109280).
Pruritus. Oral turmeric has been evaluated for the management of pruritus of various etiologies, with promising results. Details: Clinical research in patients with kidney failure shows that taking turmeric 500 mg orally three times daily for 8 weeks decreases symptoms of uremic pruritus by 1.9-fold when compared with placebo (89724). Also, a small clinical study in patients with sulfur mustard-induced chronic pruritus shows that taking a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 1 gram plus extract from black pepper or long pepper (Bioperine) daily for 4 weeks reduces pruritus severity and improves quality of life when compared with placebo (81120,81176).

POSSIBLY INEFFECTIVE

Alzheimer disease. Neither oral turmeric nor its constituent curcumin appears to improve cognitive function or attenuate cognitive decline in adults with this condition. Details: A small clinical trial shows that taking the turmeric constituent, curcumin, 1-4 grams daily for 6 months does not improve mental state examination scores when compared with placebo (17096). Furthermore, a meta-analysis of this study and another small clinical study in patients with Alzheimer disease shows that the turmeric group experienced greater cognitive decline when compared with placebo (100261). While this research is limited by small study sizes and heterogeneous patient populations, the current evidence does not support the use of turmeric in patients with this condition.
Peptic ulcers. Oral turmeric does not seem to improve the healing of peptic or gastric ulcers when compared with placebo or liquid antacids. Details: Some clinical research shows that taking turmeric 2 grams three times daily for 8 weeks does not improve the healing of peptic ulcers when compared with placebo in Vietnamese patients (81444). Also, taking powdered turmeric rhizome 250 mg four times daily for 6 weeks seems to be less effective than a liquid aluminum-magnesium-hydroxide antacid for promoting gastric ulcer healing (81284).

Acne. Although there has been interest in using topical turmeric for acne, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Age-related cognitive decline. Some small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve cognition in elderly patients experiencing cognitive decline. Details: A meta-analysis of three small clinical trials shows that curcumin modestly improves cognition in the elderly (100261). One of these clinical trials shows that taking a specific brand of curcumin (Theracurmin, Theravalues Corp.) 90 mg twice daily for 18 months improves long-term memory and attention when compared with placebo in middle-aged and older adults with or without mild cognitive impairment (96161).
Amenorrhea. Although there has been interest in using oral turmeric for amenorrhea, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Ankylosing spondylitis. Although there has been interest in using oral turmeric for ankylosing spondylitis, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Aromatase inhibitor-induced arthralgia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for aromatase inhibitor-induced arthralgia. Details: A small clinical trial in patients experiencing aromatase inhibitor-induced arthralgia shows that taking curcuminoids as a nanoemulsion (Curcumin C3 Complex, Sabinsa Corporation) 200 mg daily for 3 months does not improve grip strength or joint symptoms when compared with placebo (113345). However, this study may have been underpowered to detect a difference between groups.
Asthma. Some small clinical studies suggest that oral turmeric, as an adjunct to conventional asthma treatment, does not improve lung function or symptoms in adults and children with asthma. Details: One small clinical study in adults with mild to moderate asthma shows that adjuvant therapy with turmeric as curcumin 500 mg twice daily for 30 days does not improve lung function based on FEV1, or improve symptoms such as dyspnea, wheezing, cough, or tightness, when compared to standard treatment alone (99349). A small clinical trial in children 7-18 years of age with moderate to severe asthma shows that adding turmeric 500-1000 mg (containing 20-40 mg curcuminoids) daily for 6 months to standard therapy does not improve overall asthma symptoms when compared with placebo and standard therapy, although it may decrease the frequency of nighttime awakenings and the use of rescue inhalers (99348). Due to their small sizes and high drop-out rates, these studies may have been underpowered to detect a difference between groups.
Athletic performance. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for athletic performance. Details: Preliminary clinical research in middle-aged male long-distance runners shows that taking a turmeric extract providing 2 grams of curcumin 95% and piperine 5% daily for 6 weeks does not improve aerobic capacity when compared with placebo (109286).
Benign prostatic hyperplasia (BPH). It is unclear if oral curcumin, a constituent of turmeric, is beneficial in BPH. Details: A clinical study in patients with BPH shows that taking curcumin 2250 mg once daily along with tamsulosin and finasteride for 6 months improves lower urinary tract symptoms related to storage, but not overall symptoms or symptoms related to voiding, by about 35%, compared with 25% in those receiving tamsulosin and finasteride alone. Periprostatic fat thickness, quality of life, and erectile function also were improved (106799).
Beta-thalassemia. It is unclear if oral turmeric is beneficial for iron overload in patients with beta-thalassemia. Details: A small clinical study in patients with beta-thalassemia major and iron overload shows that taking turmeric extract containing curcumin 500 mg twice daily for 12 weeks modestly reduces non-transferrin bound iron (NTBI) by 0.6 micromol/L, but not hemoglobin, transferrin saturation, total iron binding capacity, ferritin, or hepcidin, when compared with placebo (99306). Another small clinical study in adult males with beta-thalassemia intermedia and iron overload shows that taking a higher dose of curcumin 500 mg three times daily for 12 weeks modestly reduces serum iron and ferritin turmeric levels and transferrin saturation when compared with placebo (108871).
Bruises. Although there has been interest in using topical turmeric to alleviate bruising, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Cachexia. It is unclear if oral curcumin, a constituent of turmeric, is beneficial for cancer cachexia. Details: A small clinical trial in patients with cancer anorexia-cachexia syndrome shows that taking curcumin 800 mg twice daily for 8 weeks does not reduce weight loss or improve body composition or handgrip strength when compared with placebo (109283).
Canker sores. Some preliminary research suggests that topical curcumin, a constituent of turmeric, is beneficial for minor canker sores. Details: Preliminary clinical research in young adults with minor canker sores shows that applying a 2% curcumin oral gel for 6 months reduces ulcer size, pain, and recurrence rate and increases healing rate similarly to 0.1% triamcinolone oral paste (104962). The validity of the study is limited by a lack of investigator blinding and the lack of an intention to treat analysis. Another small clinical study shows that applying a 1% curcumin nanomicelle gel (SinaCurcumin Pharmaceuticals) on lesions three times daily for one week is modestly more effective than applying a 2% curcumin gel for reducing pain and ulcer size (109282). The validity of this finding is limited by the lack of a non-curcumin comparator group.
Carpal tunnel syndrome. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. It is unclear if topical curcumin, a constituent of turmeric, is beneficial for carpal tunnel syndrome. Details: A moderate-sized clinical study in adults with mild to moderate carpal tunnel syndrome shows that taking a combination product containing turmeric, alpha-lipoic acid, acetyl-L-carnitine, phosphatidylserine, and vitamins C, E, B1, B2, B6, and B12 twice daily for 60 days reduces symptom severity and pain but does not improve measures of hand and wrist function when compared with control (111702). The validity of these effects is limited by a lack of blinding. The study may also be inadequately powered to detect a difference between groups. Additionally, it is unclear if the effects are due to turmeric, other ingredients, or the combination. Topical turmeric has also been investigated. A small clinical study in patients with mild to moderate carpal tunnel syndrome shows that applying a 1% curcuminoid gel (Sinanomin) to the wrists twice daily for 8 weeks modestly decreases symptom severity and improves function when compared with a placebo gel. However, there was no change in electrodiagnostic testing of the injury. All patients also used a night splint (113356).
Chemotherapy-induced acral erythema. It is unclear if oral or topical turmeric reduces the risk for acral erythema from capecitabine. Details: A small clinical trial in adults with cancer shows that taking turmeric 4 grams daily for 6 weeks starting at the beginning of treatment with capecitabine does not reduce the incidence of acral erythema overall; however, it does seem to reduce acral erythema grade 2 or higher when compared with expected incidence rates (99309). Topical turmeric has also been evaluated. A clinical study in patients with colorectal, gastric, pancreatic, or breast cancer receiving capecitabine shows that applying a specific ointment (Alpha) standardized to contain curcumin extract 0.5% and henna extract 10% to the soles and palms twice daily, beginning on day 1 of chemotherapy and continued for 4 cycles, does not prevent acral erythema or improve World Health Organization severity scores when compared with placebo. A post-hoc analysis suggests that there may have been a trend toward delayed onset and progression; however, this study was not structured to assess these outcomes (108874).
Chemotherapy-induced constipation. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced constipation. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of constipation when compared with placebo (107111).
Chemotherapy-induced diarrhea. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced diarrhea. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks does not reduce symptoms of diarrhea when compared with placebo (107111).
Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral curcumin reduces CINV. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of nausea, but not vomiting, in the second and third months after the start of treatment when compared with placebo (107111).
Chemotherapy-induced peripheral neuropathy. It is unclear if oral curcumin reduces symptoms of chemotherapy-induced peripheral neuropathy. Details: A small clinical study in patients with various forms of cancer receiving standard chemotherapy for that cancer type shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg twice daily for 9 weeks modestly reduces symptoms of chemotherapy-induced peripheral neuropathy over a three-month period when compared with placebo (107111).
Chronic kidney disease (CKD). It is unclear if oral turmeric is beneficial for CKD. Details: A meta-analysis of four small clinical trials in patients with CKD related to diabetic nephropathy or lupus nephritis shows that taking curcumin or turmeric for 0.5-4 months moderately reduces proteinuria when compared with placebo (109276). Also, a small clinical trial in children and young adults ages 6-25 years with vascular dysfunction related to autosomal dominant polycystic disease (PKD) shows that curcumin powder 25 mg/kg daily for 12 months does not improve vascular function or kidney function when compared with placebo (107117).
Colorectal adenoma. It is unclear if oral turmeric is beneficial for managing colorectal adenoma. Details: Preliminary clinical research in adults with familial adenomatous polyposis shows that taking curcumin 1500 mg twice daily for 12 months does not reduce the quantity or size of lower intestinal adenomatous polyps when compared with placebo (97427). A very small clinical trial in patients with familial adenomatous polyposis shows that taking 8 capsules daily of a turmeric extract, in a formulation also containing pepper fruit, spirulina, seaweed, and ginger root, for 6 months does not affect total polyp number or burden when compared with placebo. However, both number and burden were modestly reduced in the left colon. Each capsule provided curcuminoids 123.65 mg and turmerones 26.79 mg (110223).
Colorectal cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of colorectal cancer. Details: A small clinical trial in patients undergoing chemotherapy following colorectal cancer surgery shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily for 8 weeks modestly improves some measures of quality of life when compared with placebo (107109). In addition, a small clinical study in people at high risk for colorectal cancer, such as those who smoke, shows that taking the turmeric constituent, curcumin, 4 grams daily for 30 days can reduce the number of precancerous rectal aberrant crypt foci (18204). It is not clear if this results in a reduced risk for colorectal cancer.
Coronary artery bypass graft (CABG) surgery. One small study suggests that oral turmeric may reduce the risk for myocardial infarction after CABG surgery. Details: Preliminary clinical research shows that taking the turmeric constituent, curcuminoids, 4 grams daily in four divided doses, beginning 3 days prior to surgery and continuing for 5 days post-surgery, decreases the relative risk of myocardial infarction following CABG by approximately 56% when compared with placebo (81143).
Coronavirus disease 2019 (COVID-19). It is unclear if oral turmeric or its constituent, curcumin, is beneficial for reducing symptoms of COVID-19. Details: Small studies have evaluated curcumin as an adjunctive therapy in adults hospitalized with confirmed COVID-19. Patients in these studies also received treatments such as antimicrobials, anti-inflammatory medications, anticoagulants, antiretrovirals, and immunosuppressants (104966,105393,107119). One study shows that adding curcumin reduces the duration of shortness of breath by 6-9 days when compared with patients who received other treatments in combination with probiotics. However, there were no differences in the duration of other symptoms, including fever, cough, or sore throat. Subgroup analyses suggest that taking curcumin may improve oxygenation and reduce the need for supplemental oxygen or ventilation (105393). Another study shows that adding curcumin modestly reduces the time to resolution of COVID-19 symptoms, the length of supplemental oxygen use, and the likelihood for deterioration in the patients' condition when compared with patients who received other treatments alone (104966). A third study shows some benefit of curcumin on fever and cough when compared with baseline; however, it is unclear if any changes were significant when compared with placebo (107119). Doses of curcumin used in these studies include curcumin 525 mg with piperine 2.5 mg (C3 Complex, SamiDirect) twice daily, starting at admission and continuing for 14 days (105393), or a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 2 weeks or 240 mg daily in divided doses for 7 days (104966,107119). Limitations of these studies include the small number of patients with severe symptoms, the large number of outcomes evaluated, the inconsistencies in other treatments used, the lack of clarity related to presentation of some results, and, in most cases, a lack of blinding. Turmeric has also been evaluated in adults in the outpatient setting with suspected or confirmed mild to moderate COVID-19. One small clinical study shows that taking curcumin (SinaCurcumin, ExirNanoSina) 80 mg twice daily for 14 days in addition to other COVID-19 treatments (mainly hydroxychloroquine and azithromycin) reduces the duration of cough, chills, myalgia, and smell and taste disturbance, but not dyspnea, fever, sore throat, or others, by 1-2 days when compared with placebo with other treatments (106802). The validity of this study is limited by the lack of confirmatory diagnosis at baseline and lack of consistency with other treatments, as well as the unclear reporting of symptom duration in relation to the initiation of treatment. Another small clinical study in outpatients confirmed to have COVID-19 shows that taking curcumin 1000 mg plus piperine 10 mg (Sami Labs Limited) daily for 14 days modestly improves weakness, but not cough, pain, headache, difficulty breathing, or biochemical indices, when compared with placebo (109278). Some research has also examined the effect of turmeric as part of a polyherbal combination. Clinical research in patients hospitalized for moderate COVID-19 symptoms shows that using an Ayurvedic formulation 1776 mg twice daily containing turmeric, ashwagandha, ginger, and Boswellia serrata (BV-4051) for 14 days modestly reduces the duration of illness and reduces the severity of fever, cough, and smell and taste dysfunction when compared to placebo. There was no beneficial effect on other symptoms, including nasal congestion, breathing difficulty, headache, and gastrointestinal symptoms. More than half of the patients were also treated with remdesivir which did not impact the majority of these findings (109899).
Crohn disease. It is unclear if oral turmeric is beneficial for improving symptoms of active Crohn disease. Details: Some clinical research shows that taking the turmeric constituent, curcumin, 1.08 grams daily for one month, then 1.44 grams daily for one month, can reduce bowel movements, diarrhea, and abdominal pain when compared to baseline in patients with Crohn disease (79730). The validity of these findings is limited by the lack of a comparator group.
Denture stomatitis. Topical turmeric may be beneficial for treating denture stomatitis. Details: A small clinical study in patients with denture stomatitis shows that applying topical curcumin gel (Curenext, Abbott Laboratories) three times daily for 2 weeks resolves denture stomatitis lesions similarly to clotrimazole ointment (106797).
Diabetes. Low-quality clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve glycemic control in patients with diabetes. Details: A meta-analysis of small clinical trials in patients with diabetic kidney disease shows that curcumin reduces levels of fasting glucose by approximately 8.3 mg/dL when compared with placebo. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). Preliminary clinical research included in the analysis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL (104149). Other meta-analyses of low- to moderate-quality clinical studies in patients with a variety of conditions including type 2 diabetes show that taking turmeric extract, curcumin, or curcuminoids for 4-36 weeks improves glycated hemoglobin (HbA1c) by 0.4-0.7% and reduces fasting glucose by approximately 13 mg/dL when compared with placebo or conventional treatment (106806,108877,113604). The validity of these findings is limited by the heterogeneity of the included studies and broad curcuminoid doses ranging from 46-1500 mg daily. Conversely, other meta-analyses in patients with type 2 diabetes show that curcumin does not reduce HbA1c or insulin levels when compared with placebo (104965,108877,113604).
Diabetic foot ulcers. It is unclear if oral curcumin is beneficial in patients with diabetic foot ulcers. Details: Preliminary clinical research in patients with grade 3 diabetic foot ulcers shows that taking nanocurcumin 80 mg orally daily for 12 weeks does not improve glycated hemoglobin (HbA1c) or change the rate of ulcer healing when compared with placebo. Taking turmeric did result in modest decreases in fasting blood glucose, insulin levels, and insulin resistance (104972).
Diabetic nephropathy. It is unclear if oral curcumin is beneficial in patients with diabetic nephropathy. Details: Meta-analyses of two to four small clinical trials in patients with diabetic kidney disease show that curcumin modestly improves serum levels of creatinine, total cholesterol, and fasting glucose, and reduces systolic blood pressure by 4 mmHg, when compared with placebo. However, there was no effect on diastolic blood pressure, proteinuria, or serum levels of other plasma lipids or blood urea nitrogen. Curcumin was used in doses of 66.3-1670 mg daily for 2-6 months (107114). One small study included in this analysis, which evaluated patients receiving hemodialysis, shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 12 weeks reduces fasting blood glucose by about 20 mg/dL when compared with placebo (104149).
Dysmenorrhea. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in university students aged 18 to 24 in Iran with mild to severe primary dysmenorrhea and premenstrual syndrome (PMS) shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805). Conversely, a small clinical study in adults with moderately painful dysmenorrhea shows that taking a single dose of a combination product containing turmeric, Boswellia serrata, and sesame (Rhuleave-K, Arjuna Natural Private Ltd.) 1000 mg at the start of menstruation relieves menstrual cramp pain and reduces pain intensity for up to 6 hours when compared with placebo (112806). However, it is unclear if these effects are due to turmeric, other ingredients, or the combinations.
Endometriosis. It is unclear if oral turmeric is beneficial for reducing pain due to endometriosis. Details: A small clinical study in adults with endometriosis shows that taking the turmeric constituent, curcumin, 500 mg twice daily for 8 weeks does not affect pain associated with endometriosis or quality of life when compared with placebo (113603).
Erythema. Although there has been interest in using topical turmeric for reducing erythema, there is insufficient reliable information about the clinical effects of turmeric for this purpose.
Exercise-induced muscle soreness. It is unclear if oral turmeric is beneficial for reducing muscle soreness from exercise. Details: A small clinical study in healthy males shows that taking turmeric capsules containing curcumin 2.5 grams twice daily for 5 days, starting 2.5 days before exercise, slightly reduces pain from certain movements when compared with placebo (98998). Another small crossover clinical study in professional male soccer players shows that taking curcumin 500 mg (Elite Opti-Turmeric, Health Span) immediately, 12 hours, and 36 hours after a match accelerates muscle recovery and reduces delayed-onset muscle soreness when compared with medium chain triglyceride oil 1000 mg (111356). Turmeric has also been examined in combination with other ingredients. Clinical research in healthy active adults with moderate to severe exercise-induced muscle pain shows that taking a single, 1000-mg dose of turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) improves pain relief when compared with placebo, with maximal benefits within about 3 hours. The number of people needed to treat to obtain pain relief of at least 50% over a 6-hour period was 1.1 (109277).
Gingivitis. Small clinical studies suggest that oral turmeric and turmeric mouthwash may reduce the severity of gingivitis. Turmeric mouthwash appears to be similarly effective to chlorhexidine mouthwash. Details: A meta-analysis of generally preliminary clinical research shows that rinsing with a mouthwash containing curcumin for 3-4 weeks is as effective as rinsing with chlorhexidine for reducing the severity of gingivitis or plaque (106059). Mouthwashes in these studies contained 0.05% to 20% curcumin and were usually used twice daily for 3-4 weeks (81127,89723,106059). One mouthwash contained 0.05% turmeric extract and 0.005% eugenol (89723). Another small clinical trial shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily by mouth after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo in patients with gingivitis and mild periodontitis (104146).
Gout. Although there is interest in using oral turmeric for gout, there is insufficient reliable information about the clinical effects of turmeric for this condition.
Gulf war syndrome. It is unclear if oral curcumin is beneficial in patients with Gulf war syndrome. Details: A small preliminary clinical trial in patients with Gulf war syndrome shows that taking curcumin (Meriva, Indena, S.p.A.) 500 mg twice daily for 30 days reduces overall symptoms, including pain, fatigue, gastrointestinal distress, and others, by 19% when compared with baseline. Taking a higher dose of 2000 mg twice daily for an additional 30 days appears to be no more effective than the lower dose (105395).
Helicobacter pylori. Small clinical studies suggest that oral turmeric is not beneficial for eradicating H. pylori when used alone or in combination with standard triple therapy or famotidine. Details: One small clinical study in patients with H. pylori gastritis shows that taking turmeric 2.1 grams daily for 4 weeks is less effective for eradicating H. pylori than taking an omeprazole-based triple regimen for one week (80957). Another small study in adults with peptic ulcers shows that taking a specific curcumin product (C3 Complex, Sami Labs LTD) 500 mg daily for 7 days, in conjunction with standard triple therapy, does not improve H. pylori eradication rates when compared with standard triple therapy alone. The addition of curcumin increased the resolution of dyspepsia symptoms by an additional 21%, but the clinical significance of this outcome is unclear (97420). In patients with dyspepsia, most of whom tested positive for fecal H. pylori antigen, clinical research shows that taking curcuminoids (C3 Complex, Sami Labs) 500 mg with piperine (Bioperine) 5 mg daily in addition to famotidine 40 mg daily for 30 days is no more effective for reducing fecal H. pylori antigen levels than taking famotidine alone (106063).
Hypertension. It is unclear if oral curcumin is beneficial in patients with hypertension. Details: A meta-analysis of approximately 30 clinical studies in healthy adults or patients with a variety of conditions shows that taking turmeric, curcumin, curcuminoids, or nano-curcumin for 4 to 24 weeks reduces systolic blood pressure by about 2 mmHg and diastolic blood pressure by about 0.8 mmHg when compared with placebo (113602). However, these blood pressure reductions may not be clinically meaningful. In addition, most of the included studies were small and utilized heterogeneous dosing regimens.
Impaired glucose tolerance (prediabetes). Oral turmeric may modestly improve glucose control in some patients with prediabetes. Details: In overweight or obese individuals with prediabetes, clinical research shows that taking a turmeric extract (BCM95 or Cucugreen; M/s Arjuna Natural Pvt Ltd.) 500 mg daily, providing 95% curcuminoids and at least 65% curcumin, for 90 days, either alone or in combination with zinc 30 mg as zinc gluconate, results in a small reduction in fasting glucose and glycated hemoglobin (HbA1c) when compared with placebo. There was also a small benefit in insulin sensitivity (105391). Other preliminary clinical research in adults with prediabetes shows that taking 500 mg of a combination of turmeric extract and Indian gooseberry extract in a 1:2 ratio along with phosphatidylcholine (EmbliQur) twice daily for 6 months modestly reduces fasting glucose and improves insulin resistance, when compared with placebo. However, changes in most other endpoints were not significantly different from placebo. Each 500 mg capsule contained turmeric extracts 29.86% and turmeric oil 1.27% (113355). The effect of turmeric on progression to type 2 diabetes in patients with prediabetes has also been investigated. Preliminary clinical research shows that taking a turmeric extract containing curcumin 750 mg twice daily for 9 months reduces the percentage of patients with prediabetes who develop type 2 diabetes when compared with placebo (81163).
Irritable bowel syndrome (IBS). It is unclear if oral turmeric is beneficial for improving symptoms of IBS. Details: Preliminary clinical research in otherwise healthy adults with IBS shows that taking a turmeric extract (Cynara Turmeric, Lichtwer Pharma) 72-144 mg daily for 8 weeks reduces IBS symptoms by about 40% to 60% when compared to baseline (79565). The validity of this finding is limited by the lack of a comparator group. Taking a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422). It is unclear if these effects are due to turmeric, fennel, or the combination. Observational research suggests that adding a supplement (Enterofytol PLUS) providing curcumin 42 mg and berberine 200 mg twice daily for 2 months to conventional IBS treatment is associated with improvements in symptoms, such as abdominal discomfort, distension, and stool status, by up to 48% when compared with conventional treatment alone. Use of the supplement was also associated with a 64% reduced need for conventional treatments (113354).
Joint pain. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking capsules of a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 1500 mg, methylsulfonylmethane 500 mg, white willow bark extract 250 mg, ginger root concentrate 50 mg, Boswellia extract 125 mg, turmeric root extract 50 mg, cayenne 40 m H.U. 50 mg, and hyaluronic acid 4 mg in three divided doses daily for 8 weeks reduces joint pain severity by 37% compared to only 16% with placebo. However, it does not improve joint stiffness or function when compared with placebo (89560). It is unclear if these effects are due to turmeric, other ingredients, or the combination.
Juvenile idiopathic arthritis (JIA). Although there is interest in using oral turmeric for JIA, there is insufficient reliable information about the clinical effects of turmeric for this condition.
Knee pain. It is unclear if oral turmeric is beneficial for knee pain. Details: Clinical research in individuals with knee pain not related to existing arthritis shows that taking turmeric extract (TurmXTRA 60N; Inventia Healthcare Ltd. and Laila Nutraceuticals) 250 mg, providing 60% curcuminoids, once daily for 90 days modestly reduces pain associated with walking 80 meters when compared with placebo. The time taken to walk 80 meters and to climb nine steps was reduced by 4-5 seconds (105396).
Lichen planus. Evidence is conflicting on whether turmeric is beneficial for lichen planus. Details: A meta-analysis of several small, heterogeneous, mostly low-quality clinical and observational studies in adults with oral lichen planus shows that oral or topical curcumin with or without corticosteroids for 2-12 weeks does not improve erythema, lesion size, or pain when compared with control (113605). Similarly, a network meta-analysis of small clinical trials in patients with oral lichen planus shows that applying topical turmeric gel does not improve symptoms, clinical resolution, clinical scores, or reduce pain when compared with other available interventions (111640). However, small individual clinical studies have shown some benefit in using turmeric for lichen planus. A small clinical study shows that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) containing curcuminoids 6000 mg daily in three divided doses for 12 days can reduce erythema and ulceration associated with lichen planus when compared with placebo (81109). Another small clinical study shows that taking a nanocurcumin product (SinaCurcumin, ExirNanoSina) 80 mg orally once daily for 1 month reduces oral lichen planus lesion size, pain, and burning similarly to prednisolone 10 mg taken orally once daily for 1 month (104961).
Metabolic syndrome. It is unclear if oral turmeric is beneficial for metabolic syndrome. Details: Research is conflicting on how turmeric, curcumin, and other formulations affect various measures of metabolic syndrome. Some clinical research and a meta-analysis of 13 clinical studies in patients with metabolic syndrome show that taking turmeric or curcumin decreases low-density lipoprotein (LDL) cholesterol, waist circumference by 2 cm, fasting blood glucose by 9 mg/dL, and diastolic blood pressure by 3 mmHg and increases high-density lipoprotein (HDL) cholesterol by 5 mg/dL when compared with placebo. However, other research shows that turmeric or curcumin have no effect on body weight, lipids, blood pressure, or blood glucose when compared with placebo (98999,99311,105400,109284,111347,112118). The validity of these effects is limited by high heterogeneity within the included studies and incomplete information about randomization and blinding. Studies have used turmeric, curcumin, and curcumin extract 80-2400 mg, in divided doses, daily for 4-12 weeks, nano-curcumin 80 mg daily for 12 weeks, or calebin A (CurCousin, Sabinsa), which is a constituent of turmeric, 25 mg twice daily for 3 months (98999,99311,105400,109284,111347,112118). Also, taking crude or phosphorylated curcuminoids 1 gram daily for 6 weeks does not improve sleep or reduce weight in these patients (105397).
Migraine headache. It is unclear if oral curcumin is beneficial for migraine headache. Details: A small clinical trial in females with regular migraines shows that taking curcumin 500 mg twice daily for 8 weeks reduces the severity and duration, but not the frequency, of migraine headaches when compared with placebo. In individuals taking curcumin, the duration of headache per month was reduced by approximately 10.3 hours from baseline (107116).
Myocardial infarction (MI). It is unclear if oral curcumin is beneficial for reducing myocardial injury following a MI. Details: Clinical research in patients with an acute MI shows that taking curcuminoids 500 mg plus piperine (Bioperine) 5 mg daily (Sami Labs) for 8 weeks does not improve ejection fraction, serum levels of cardiac troponin 1, blood pressure, levels of fasting blood glucose, or kidney function parameters when compared to placebo. However, there were some modest benefits on levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, glycated hemoglobin, and certain liver enzymes such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) (107115). The validity of this study is limited by its short duration and relatively small sample size.
Obesity. Oral turmeric might modestly improve weight loss, although any effect is unlikely to be clinically significant. Details: Multiple meta-analyses of small, mostly low-quality clinical studies in adults with a variety of comorbid conditions show that taking various forms and doses of turmeric or curcumin results in an average weight loss of about 0.6-1 kg, a decrease in body mass index (BMI) of about 0.2-0.5 kg/m2, and a decrease in waist circumference of about 1.3 cm when compared with control (102345,111351,111352). A sub-analysis of dose and duration shows that a reduction in waist circumference only occurs with curcumin daily doses above 1000 mg, and duration of treatment longer than 8 weeks (102345).
Oral submucous fibrosis. Small studies suggest that topical or oral curcumin might be beneficial for oral submucous fibrosis. However, the research is heterogenous with respect to outcomes, comparators, and the turmeric preparations, doses, and routes of administration utilized. Details: A meta-analysis of 3 small clinical trials shows that turmeric modestly improves mouth opening when compared with control. In addition, a systematic review of 11 studies shows that turmeric improves overall symptoms, including mouth opening, tongue protrusion, burning sensation, and cheek flexibility. However, studies were small with short duration and used variable dosing strategies. Most trials have studied oral turmeric 300-400 mg, either alone or with black pepper 100 mg or piperine 5 mg, for 3-6 months. Less commonly, turmeric was provided in lozenge form (105399). Also, a network meta-analysis suggests that the turmeric constituent curcumin with or without piperine is most the effective for reducing tongue protrusion when compared indirectly with various medical and antioxidant therapies; however, this analysis suggests that curcumin does not rank among the most effective interventions for improving mouth opening, burning sensation, or cheek flexibility (113514). Other preliminary clinical research shows that taking a specific oral product containing curcumin 300 mg and piperine 5 mg (Turmix tablets, Sanat Products), three times daily for 12 weeks, improves mouth opening, burning sensation, and tongue protrusion when compared with baseline, but not when compared with an antioxidant product containing alpha-lipoic acid, beta-carotene, copper, lycopene, selenium, and zinc. Mouth opening is further improved by concurrent use of a mouthwash (Turmix mouthwash, Sanat Products), containing 0.1% w/v turmeric extract (standardized to 95% curcumin), with thymol, eucalyptol, clove oil, mentha oil, and tea tree oil, twice daily for 12 weeks (102347). A small clinical study shows that applying topical curcumin gel (Curenext, Abbott Laboratories) 5 mg daily in 3-4 divided doses for 6 weeks, in combination with oral physical therapy, improves mouth opening similarly to using an aloe vera gel in combination with oral physical therapy. However, decreases in burning sensation are greater with aloe gel than curcumin gel (104967). It is not clear whether the gels, oral physical therapy, or the combination of both is responsible for the outcome. Finally, clinical research shows that applying a paste providing turmeric and holy basil 10 grams each, mixed in 10 mL of honey, to the oral mucosa 4 times daily for 3 months modestly improves mouth opening, tongue protrusion, and burning sensation and reduces the presence of fibrous bands when compared with taking a vitamin B supplement. There was no effect on the shape of the uvula (113325).
Pain (acute). Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute musculoskeletal pain shows that taking a specific combination product containing turmeric and Boswellia serrata extracts in black sesame oil (Rhuleave-K; Arjuna Natural Private Ltd.) 1000 mg daily for 7 days is as effective as acetaminophen 1000 mg daily for pain relief, onset of pain relief, and onset of maximal pain relief (109287). This study is limited by its lack of blinding and placebo control. Additionally, the dose of acetaminophen used in this study is below the standard recommended daily dose.
Periodontitis. There is limited evidence on the oral or topical use of turmeric or its constituent curcumin in patients with periodontitis. Details: A meta-analysis of heterogenous clinical studies in patients with chronic periodontitis suggests that use of local delivery gel products, usually turmeric 2% or a specific product containing curcumin (Curenext), modestly reduces pocket depth when compared with routine products, such as chlorhexidine. However, limited research suggests that curcumin products do not affect plaque or gingivitis measures, and curcumin irrigation does not affect pocket depth based on limited research (107108). A small preliminary clinical study in patients with severe chronic periodontitis shows that placing curcumin gel 2 mg on one side of the mouth along with scaling and root planing (SRP) reduces plaque and probing pocket depth, but not gingival index, when compared with SRP alone (101339). The use of oral curcumin has also been investigated. A small clinical trial in patients with gingivitis and mild periodontitis shows that taking a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily after breakfast for 4 weeks reduces the severity of gingivitis and gingival bleeding, but not plaque, when compared with placebo (104146).
Physical performance. It is unclear if oral turmeric may be beneficial for improving physical performance in older adults. Details: A very small clinical study in moderately functioning, sedentary adults over age 65 with low-grade chronic inflammation shows that that taking a specific turmeric extract (Curcumin C3 Complex, Sabinsa Corporation) 500 mg twice daily for 12 weeks does not improve measures of physical function, walking speed, or muscle strength when compared with placebo (111357). However, this study may have been inadequately powered to detect any possible differences between groups.
Polycystic ovary syndrome (PCOS). Small clinical studies suggest that oral curcumin may improve some metabolic parameters in patients with PCOS, but these improvements may not be considered clinically significant. Details: Clinical research in patients with PCOS shows that taking curcumin 500 mg one to three times daily for 6-12 weeks improves some metabolic parameters (104968,105394,106795). Conversely, a small clinical study in patients aged 18 to 45 with PCOS in Iran shows that taking curcumin 1000 mg daily for 12 weeks modestly reduces fasting glucose but does not improve other metabolic parameters when compared with placebo. Taking curcumin also did not improve testosterone levels or hirsutism scores (111355). Meta-analyses show that taking curcumin modestly decreases body mass index (BMI) and improves measures of glycemic control, including fasting glucose and insulin resistance, and levels of total cholesterol when compared with placebo or metformin alone. However, effects on high-density lipoprotein (HDL) cholesterol levels were mixed and there was no effect on low-density lipoprotein (LDL) cholesterol or triglyceride levels (105394,106795,110219). Other preliminary clinical research shows that taking curcumin decreases plasma dehydroepiandrosterone and fasting plasma glucose levels when compared with placebo (104968). Some clinical research also shows that taking nano-curcumin (SinaCurcumin, ExirNanoSina) 80 mg daily for 3 months is beneficial in patients already taking metformin 1500 mg daily. Taking curcumin had modest beneficial effects on fasting insulin and insulin resistance, as well as levels of testosterone, LDL cholesterol, HDL cholesterol, and triglycerides, when compared with metformin alone. There was no effect of curcumin on body weight, fasting blood glucose, or other hormones (106060).
Postoperative pain. Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly reduce pain in various postoperative recovery settings. Details: One small clinical study in patients undergoing laparoscopic cholecystectomy shows that taking curcumin 2 grams daily reduces postoperative pain, fatigue, and the need for analgesics by the second postoperative week when compared with placebo (81099). In patients undergoing surgery for inguinal hernia and/or hydrocele, taking curcumin 1.2 grams daily for 5 days reduces inflammation and tenderness by the sixth postoperative day when compared with placebo (81206). Curcumin was taken in 3-4 divided doses daily in these studies. Finally, taking a single dose of curcumin 200 mg after surgical removal of impacted third molars modestly reduces acute postoperative pain when compared with taking mefenamic acid 500 mg (99305).
Premenstrual syndrome (PMS). It is unclear if oral turmeric may be beneficial for improving symptoms of PMS. Details: Some preliminary clinical research in patients with PMS shows that taking curcumin 100 mg twice daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation, improves physical, behavioral, and mood symptoms, as well as overall severity of symptoms, when compared with placebo (97433). Conversely, in university students aged 18 to 24 in Iran with mild to severe PMS and primary dysmenorrhea, a clinical study shows that taking a specific combination product containing curcumin 500 mg plus extract from black pepper 5 mg (C3 Complex, Sami Labs) daily, starting 7 days prior to menstruation and continuing for 3 days after menstruation for 3 consecutive menstrual cycles, does not improve the severity of symptoms when compared with placebo (106805).
Prostate cancer. It is unclear if oral turmeric is beneficial for the prevention or treatment of prostate cancer. Details: One small clinical study shows that taking curcumin 1.8 grams orally three times daily for 7 days, starting 4 days prior to docetaxel and prednisone treatment and continuing for up to 6 cycles, reduces PSA levels by at least half in 59% of patients when compared to baseline. Also, all patients with measurable lesions showed at least stable disease after treatment, and 40% of patients showed partial response when compared with baseline (96132). It is unclear if the addition of turmeric is beneficial when compared with docetaxel and prednisone alone. In contrast, an additional small clinical trial shows that taking curcumin 6 grams daily for 7 days every 3 weeks, starting four days before docetaxel, does not improve PSA levels or progression-free or overall survival when compared with docetaxel alone (105392).
Psoriasis. Evidence is limited to one small study of topical use in patients with scalp psoriasis. Details: Preliminary clinical research in adults with scalp psoriasis shows that applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves overall symptoms and quality of life when compared with a placebo tonic (97429).
Quality of life. Some preliminary clinical research suggests that oral curcumin might improve quality of life in patients with various chronic conditions. Details: Small or low-quality clinical trials in various patient populations show that taking curcumin improves at least some measures of quality of life when compared with placebo. Research has been conducted in patients with cancer, sulfur mustard-induced chronic pruritus, benign prostatic hyperplasia (BPH), or irritable bowel syndrome (IBS). Studies have evaluated curcumin 2250 mg once daily for 6 months, a specific combination product (C3 Complex, Sami Labs LTD) containing curcumin 500-1000 mg plus piperine (Bioperine) daily for 4-9 weeks, or a combination product (CU-FEO, Alfa Wasserman S.p.A.) containing curcumin 42 mg and fennel essential oil 25 mg per capsule twice daily for 60 days (81120,81176,97422,106799,107109,107111). Also, in patients with scalp psoriasis, applying a tonic of turmeric to the scalp twice daily for 9 weeks modestly improves quality of life when compared with a placebo tonic (97429).
Radiation dermatitis. It is unclear if oral or topical turmeric is beneficial for reducing the severity of radiation dermatitis. Details: A meta-analysis of 4 clinical studies in patients with breast cancer shows that taking curcumin 500-2000 mg three times daily for 3-7 weeks or applying curcumin gel 500 mg three times daily for 7 weeks reduces the radiation dermatitis severity score by about 0.5 points (on a 4-point scale) when compared with placebo or other control (111354). The validity of this analysis is limited by the heterogeneity of the included studies. However, a small clinical study in patients with breast cancer shows that taking nanocurcumin 80 mg twice daily during and for up to 2 weeks after treatment does not reduce skin reaction severity overall, but does modestly reduce pain, when compared with taking placebo. Also, there was a small reduction in skin reaction severity near the end of the study. All patients also used aloe vera leaf as part of the hospital protocol (109281). Another small preliminary clinical study in head and neck cancer patients shows that a specific cream (Vicco turmeric cream, Vicco Laboratories) containing turmeric and sandalwood oil, applied 5 times daily during radiation therapy, seems to reduce frequency and severity of radiation dermatitis when compared with baby oil (99307).
Radiation proctopathy. It is unclear if oral turmeric is beneficial for preventing proctitis or cystitis in patients receiving radiotherapy for prostate cancer. Details: A small clinical study in patients with prostate cancer shows that taking a specific nanocurcumin product (SinaCurcumin, ExirNanoSina) 120 mg daily, for 3 days before and also during a course of radiotherapy, does not reduce the occurrence of proctitis or cystitis when compared with placebo (100259). This study may have been underpowered to detect small treatment effects.
Respiratory tract infections. Although there is interest in using oral turmeric for various respiratory tract infections, including bronchitis and the common cold, it has not been clinically evaluated.
Rheumatoid arthritis (RA). Small clinical studies suggest that oral curcumin, a constituent of turmeric, may modestly improve some symptoms of RA. Details: Meta-analyses of small clinical trials in patients with RA show that taking curcumin alone or with other treatments modestly reduces overall RA symptoms, pain, and markers of inflammation when compared with control groups, including placebo or other treatments. However, some research shows that there is no beneficial effect on tender or swollen joint count from the limited available clinical research (109280,111358), while other research shows that there is a benefit (112117). Clinical studies have evaluated curcumin 120-1200 mg daily for 2 weeks to 3 months (11149,18205,96129). The validity of these findings is limited by the small size of the studies, and in some cases, the lack of a comparator group.
Sarcopenia. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly patients with sarcopenia shows that taking a specific slow-release product containing turmeric, protein, carbohydrate, and fiber (Cureit, Aurea Biolabs), 500 mg orally daily for 3 months, increases handgrip strength by about 1% and distance walked before feeling tired by about 6% when compared with placebo. It also increases weightlifting capacity by about 6% from baseline, compared with a 5% decrease from baseline in those taking placebo (104973). It is unclear whether these small changes are clinically meaningful.
Schizophrenia. Although there is interest in using oral turmeric for improving cognitive function in patients with schizophrenia, there is insufficient reliable information about the clinical effects of turmeric for this use.
Sepsis. It is unclear if oral curcumin, a constituent of turmeric, is beneficial in patients with sepsis. Details: A small clinical trial in patients admitted to the intensive care unit (ICU) with sepsis shows that a specific nanoparticle formulation of curcumin (SinaCurcumin, ExirNanoSina), 80 mg dissolved in water and administered via gastric tube following lavage twice daily for 10 days does not affect length of ICU stay, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, blood pressure, or heart rate when compared with placebo (108873).
Smoking cessation. Oral turmeric has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing turmeric 50 mg, ashwagandha, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, and holy basil (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is unclear if these effects are due to turmeric, other ingredients, or the combination.
Stress. It is unclear if oral turmeric is beneficial for reducing occupational stress in healthy adults. Details: A small clinical trial in healthy adults with occupational stress-related anxiety and fatigue shows that taking a specific type of turmeric (CurQfen, Akay Flavours and Aromatics Pvt Ltd.) that contains fenugreek dietary fiber for improved bioavailability at a dose of 500 mg twice daily for 30 days reduces stress and fatigue and improves quality of life when compared with placebo, and also when compared with a standard curcumin supplement with lower bioavailability (99308).
Stroke. It is unclear if oral turmeric is beneficial for stroke. Details: A small clinical study conducted in Iran in adults with a recent ischemic stroke shows that taking curcumin 500 mg and piperine, a pepper constituent, 5 mg (Sami Lans, India) daily for 12 weeks reduces carotid intima-media thickness, triglycerides, total cholesterol, and systolic and diastolic blood pressure, but does not improve low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or quality-of-life indicators when compared with placebo (113601). The validity of this study is limited by the lack of statistical adjustment for multiple comparisons which can lead studies to erroneously show differences between treatment groups.
Systemic lupus erythematosus (SLE). There is limited evidence on the oral use of turmeric in adults with lupus nephritis. Details: Preliminary clinical research in adults with lupus nephritis shows that taking turmeric 1.5 grams daily in three divided doses for 3 months reduces systolic blood pressure and improves kidney function when compared to baseline (81104). The validity of this finding is limited by the lack of a comparator group.
Tuberculosis. It is unclear if oral turmeric is beneficial in patients receiving treatment for tuberculosis. Details: A small clinical study in adults receiving antituberculosis treatment shows that taking a formulation containing turmeric 0.5 grams and Tinospora cordifolia 0.5 grams twice daily for 4 months can reduce levels of Mycobacterium tuberculosis in the sputum and improve lesion healing when compared with antituberculosis treatment alone. Also, liver toxicity associated with the antituberculosis treatment seems to be reduced when administered with this formulation (80424). It is unclear if these effects are due to turmeric, Tinospora cordifolia, or the combination.
Ulcerative colitis. It is unclear if oral or rectal turmeric, or its constituent, curcumin, is beneficial in adults with ulcerative colitis. Details: Although two small clinical studies in adults with ulcerative colitis show that taking oral turmeric extract 2-3 grams daily for 1-6 months improves the rate of remission and reduces relapse rate (79966,97423), a meta-analysis of these studies and one additional clinical study shows that turmeric does not improve remission rates when compared with placebo (99000). A specific product (Cur-Cure, Bara Herbs Inc) was used in some of these studies. Reasons for the conflicting findings are unclear, but may be due to small patient populations, concerns about blinding, and the inclusion of patients who were also taking immunomodulating drugs. It may also be due to differences in how a study measures remission. A meta-analysis of small clinical studies in patients with mild to moderate ulcerative colitis shows that adding oral curcumin 0.5-3 grams daily to standard treatment for 1-6 months may improve clinical remission rates, but not endoscopic remission rates, when compared with placebo (108872). However, the validity of this finding is limited by the small number of studies that evaluated endoscopic remission. A small clinical study shows that administering an enema form of turmeric extract (NCB-02, Himalaya Drug Company) as 20 mL, containing turmeric extract 140 mg, daily for 8 weeks increases response rate from 50% to about 93% and increases remission rate from about 31% to 71% when compared with placebo in patients with active ulcerative colitis. However, patients using the turmeric extract enema for shorter durations did not improve when compared with placebo (89729). Turmeric has also been investigated in combination with the Mediterranean diet. A small clinical trial shows that taking curcumin (VeNatura Curcumin Supplement) 800 mg twice daily while following the Mediterranean diet for 8 weeks is no more effective for improving ulcerative colitis symptom severity than following the Mediterranean diet without supplemental curcumin (113339).
Uveitis. It is unclear if oral curcumin is beneficial for uveitis. Details: Observational research in patients with acute non-infectious uveitic macular edema shows that taking a specific hydrophilic curcumin product (Cucrcuwin, Diabec, Alfa Intes) 60 mg twice daily for 6 months, in conjunction with standard corticosteroid treatment, and then alone for an additional 6 months, modestly improves best corrected visual acuity, but not macular thickness or intraocular pressure, when compared with standard treatment alone for 6 months (107110).
Wound healing. Although there is interest in using topical turmeric for wound healing, there is insufficient reliable information about the clinical effects of turmeric for this condition. More evidence is needed to rate turmeric for these uses.

Safety view details

Below is general information about the safety of the known ingredients contained in the product Omega Memory with Curcumin. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

DOCOSAHEXAENOIC ACID (DHA) (Docosahexaenoic Acid)

LIKELY SAFE ...when used orally and appropriately. DHA has been used safely in studies lasting up to 4 years (1016,1043,6413,10321,10869,11333,90684). Fish oil supplements containing DHA have also been safely used in studies lasting up to 7 years (1016). While doses of DHA up to 4 grams orally daily have been used safely in some clinical research (6143), there is some concern that high intake of omega-3 fatty acids such as DHA might increase the risk of bleeding. For this reason, the US Food and Drug Administration (FDA) recommends that consumers limit intake of DHA plus eicosapentaenoic acid (EPA), another omega-3 fatty acid also found in fish oil, to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).

POSSIBLY SAFE ...when used intravenously and appropriately, in combination with eicosapentaenoic acid (EPA), short-term. Daily infusions with an omega-3 fatty acid-based lipid emulsion (Omegavenous 10%, Fresenius Aktiengesellschaft) providing 4.2 grams/day of DHA and EPA has been used safely for 14 days (1004).

POSSIBLY UNSAFE ...when used orally in high doses. Doses greater than 3 grams daily might decrease platelet aggregation and increase the risk of bleeding (1313). The US Food and Drug Administration (FDA) recommends that consumers limit intake of DHA plus eicosapentaenoic acid (EPA), another omega-3 fatty acid, to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).

CHILDREN: LIKELY SAFE
when used orally and appropriately. DHA is a component of some infant formula (424,1045,5708,5941,7599,14403,15003,15495,17735,48088)(48194,48266,48343,90665,90713,90716,110357). In children 7 years and older, DHA 30 mg/kg daily has been used safely for up to 4 years (90684). Also, DHA 0.4-1 grams daily has been safely used in children ages 4 years and older for up to 1 year (11333,90665,100940,104560).

CHILDREN: POSSIBLY UNSAFE
when used orally in preterm infants born less than 29 weeks gestation. Although not all findings agree (110356,110359), supplementation with an enteral emulsion containing DHA 40 mg/kg to 60 mg/kg daily might increase the risk of developing or worsening bronchopulmonary dysplasia compared to control emulsion (96523,110359).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. An intake of DHA 650 mg daily from food and/or supplements during pregnancy seems to be required to prevent a reduction in DHA status before delivery (110329). DHA is commonly used during pregnancy and lactation and is a component of some prenatal supplements. DHA is a normal component of breast milk, with higher levels in breast milk following term vs. preterm pregnancies (14393,14394,14396,14400,14403,14397,20000,47977,47994,48095)(90672,90718,110355). When taken as a prenatal supplement, DHA increases DHA levels in breast milk (90685). Doses of DHA ranging from 300-600 mg daily beginning during the first trimester of pregnancy have been used safely in clinical research (90672,90676,90687,90694). When taken during lactation, DHA increases DHA levels in breast milk (109214,110362). When initiated within 72 hours of delivery of a very preterm infant, taking DHA 1.2 grams daily increases DHA levels in breast milk within 14 days (109214). One study found that DHA supplementation during lactation increased the risk of bronchopulmonary dysplasia in breast-feeding infants born less than 29 weeks gestational age (104559); however, it is unclear if this was due to DHA or various confounding factors. The tolerable upper intake level of DHA during pregnancy or lactation has not been established; most experts recommend DHA 200-300 mg daily. While it is typically advised that this need is met by consuming 8-12 ounces of seafood weekly during pregnancy and 4-8 ounces weekly during lactation, those with nutrient deficiency or those following a vegan diet may meet this need with supplementation (95740,95741).

EICOSAPENTAENOIC ACID (EPA) (Eicosapentaenoic Acid)

LIKELY SAFE ...when fish oil or prescription EPA is used orally and appropriately as a source of EPA. Fish oil containing EPA has been used safely for up to 7 years (1016,7819,15497). While doses of prescription EPA (Vascepa, formerly ARM101, Amarin) have been used safely at doses up to 4 grams daily (91409,91410,95715,99136), there is some concern that high intake of omega-3 fatty acids such as EPA might increase the risk of bleeding. For this reason, the US Food and Drug Administration (FDA) recommends that consumers limit intake of EPA plus docosahexaenoic acid (DHA), another omega-3 fatty acid also found in fish oil, to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).

POSSIBLY SAFE ...when algal oil is used orally and appropriately as a source of EPA. A specific algal oil supplement (Almega PL) providing EPA 250 mg daily has been used with apparent safety for up to 12 weeks (103314). ...when used intravenously under the guidance of a healthcare professional. Fish oil or omega-3 fatty acid lipid emulsions containing EPA, administered intravenously for 1-4 weeks, have been safely used (1004,66042,66421,89323).

POSSIBLY UNSAFE ...when used orally in high doses. Doses greater than 3 grams daily might decrease blood coagulation and increase the risk of bleeding (1313). The US Food and Drug Administration (FDA) recommends that consumers limit intake of EPA plus DHA, another omega-3 fatty acid, to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

HUPERZINE A

POSSIBLY SAFE ...when used orally and appropriately, short-term. Huperzine A 200-800 mcg daily has been used with apparent safety in clinical trials lasting up to 6 months (3171,3561,4626,93478,93479,93480,93481,93482,93483,93485).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Huperzine A has been used with apparent safety in clinical research lasting for 1 month (4626).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

POSSIBLY SAFE ...when used orally and appropriately. Large doses up to 30 grams per day for 6 weeks (5223) and smaller doses of up to 6 grams daily for up to 24 months have been well tolerated (68839,68843,105728). ...when used subcutaneously and appropriately, short-term. Some research suggests that subcutaneous injections of 0.2 mL to 5 mL of a 5% phosphatidylcholine solution do not cause significant serious adverse effects when doses are administered up to five times and spaced apart by 2-4 weeks (15621,15623,15624,15625). ...when used topically as an emulsion also containing niacinamide for up to 12 weeks (93388).

PREGNANCY: POSSIBLY SAFE
when used orally from 18 weeks of gestation at doses of up to 5 grams daily (93386)

LACTATION:
Insufficient reliable information available; avoid using.

LIKELY SAFE ...when used orally and appropriately, short-term. Turmeric products providing up to 8 grams of curcumin have been safely used for up to 2 months (10453,11144,11150,17953,79085,89720,89721,89724,89728,101347)(81036,101349,107110,107116,107117,107118,107121,109278,109283). Turmeric in doses up to 3 grams daily has been used with apparent safety for up to 3 months (102350,104146,104148,113357). ...when used topically and appropriately (11148).

POSSIBLY SAFE ...when used as an enema, short-term. Turmeric extract in water has been used as a daily enema for up to 8 weeks (89729). ...when used topically as a mouthwash, short-term. A mouthwash containing 0.05% turmeric extract and 0.05% eugenol has been used safely twice daily for up to 21 days (89723).

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in food.

PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts; turmeric might stimulate the uterus and increase menstrual flow (12).

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food. There is insufficient reliable information available about the safety of using turmeric in medicinal amounts during lactation.

Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Omega Memory with Curcumin. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

DOCOSAHEXAENOIC ACID (DHA) (Docosahexaenoic Acid)

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Unlikely • Level of Evidence = B

Theoretically, DHA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

Although some clinical evidence suggests that DHA might reduce collagen-stimulated platelet aggregation and thromboxane release, most clinical evidence suggests that DHA alone does not affect blood clotting (11112,11113,48020). However, theoretically, when given in combination with EPA as fish oil, concomitant use with anticoagulant or antiplatelet drugs (including aspirin) might increase risk of bleeding.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, taking DHA with antidiabetes drugs might reduce the effects of these medications.

Details

In people with type 2 diabetes, including those taking oral hypoglycemic medications, DHA seems to increase fasting blood glucose levels (10321).

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Theoretically, taking DHA with antihypertensive drugs might increase the risk of hypotension.

Details

Fish oils containing DHA can lower blood pressure and might have additive effects in patients treated with antihypertensives (1001,1020,1030,1033,47944,48013,48020,48163); use with caution.

EICOSAPENTAENOIC ACID (EPA) (Eicosapentaenoic Acid)

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, EPA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

In human research, taking EPA has been shown to inhibit platelet aggregation (9930).

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Theoretically, taking EPA with antihypertensive drugs might increase the risk of hypotension.

Details

Fish oils containing EPA can lower blood pressure and might have additive effects in patients treated with antihypertensives (1001,1020,1030,1033); use with caution.

HUPERZINE A

ANTICHOLINERGIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, huperzine A might decrease the effects of anticholinergic drugs.

Details

Huperzine A has acetylcholinesterase (AChE) inhibiting effects. In animal models, huperzine A reversed cognitive deficits induced by scopolamine, an anticholinergic drug (3134,3135,55692).

CHOLINERGIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, concurrent use of huperzine A with cholinergic drugs might increase the effects and side effects of these medications.

Details

Huperzine A can inhibit acetylcholinesterase (AChE) and might cause cumulative effects if used with cholinergic drugs (3131).

None known.

ALKYLATING AGENTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.

Details

In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression (96126). However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

AMLODIPINE (Norvasc)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Taking turmeric with amlodipine may increase levels of amlodipine.

Details

Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone (107113). Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone (103099).

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.

Details

Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271). Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR) (89718,100906). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk (96137). It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes (79692,79984,80155,80313,80315,80476,80553,81048,81219). Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction (96133). Another clinical study in patients with diabetes on hemodialysis shows that taking curcumin 80 mg daily for 12 weeks can reduce blood glucose levels when compared with placebo (104149).

ANTITUMOR ANTIBIOTICS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.

Details

In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65% (96126). However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase or decrease levels of drugs metabolized by CYP1A1. However, research is conflicting.

Details

Most in vitro and animal research suggests that the turmeric constituent, curcumin, INHIBITS CYP1A1, primarily in the liver (15823,21495,80876,81411). However, some evidence from in vitro research suggests that curcumin may INDUCE CYP1A1 in the intestines (21500).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.

Details

In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2 (15823,21497,81304). However, other in vitro research suggests that curcumin does not significantly affect CYP1A2 (22000).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric might increase levels of drugs metabolized by CYP3A4.

Details

In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4 (21497,21498,21499). Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib (111644). In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition (93544).
Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans.

DOCETAXEL (Taxotere)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase blood levels of oral docetaxel.

Details

Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel (80999). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

ESTROGENS

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.

Details

In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors (21486).

GLYBURIDE (Diabeta, others)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.

Details

Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research (96133).

HEPATOTOXIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.

Details

There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses (103633,107122,109288,110221).

LOSARTAN (Cozaar)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase the effects of losartan.

Details

Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan (110897).

METHOTREXATE (Trexall, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.

Details

In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity (111644).

NORFLOXACIN (Noroxin)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.

Details

Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin (80863).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase blood levels of OATP4C1 substrates.

Details

In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs (113337). Theoretically, taking turmeric might decrease renal excretion of OATP substrates.

P-GLYCOPROTEIN SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.

Details

In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity (21472,21473,21474,21475,21476,21477,21478,21479,21480)(21482,21484,111644).

PACLITAXEL (Abraxane, Onxol)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.

Details

Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant (108876). Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel (22005). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

SULFASALAZINE (Azulfidine)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Turmeric might increase the effects and adverse effects of sulfasalazine.

Details

Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold (81131).

TACROLIMUS (Prograf)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric might increase the effects and adverse effects of tacrolimus.

Details

In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition (93544). In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499).

TALINOLOL

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Turmeric may reduce the absorption of talinolol in some situations.

Details

Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day (80079). The clinical significance of this effect is unclear.

TAMOXIFEN (Nolvadex)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.

Details

In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers (107123).

TOPOISOMERASE I INHIBITORS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.

Details

In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71% (96126). However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have.

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Turmeric might increase the risk of bleeding with warfarin.

Details

One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10 (100906). Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271), which may produce additive effects when taken with warfarin.

Report an Adverse Reaction to Omega Memory with Curcumin

Adverse Effects view details

Below is general information about the adverse effects of the known ingredients contained in the product Omega Memory with Curcumin. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

DOCOSAHEXAENOIC ACID (DHA) (Docosahexaenoic Acid)

General ...Orally, DHA is generally well-tolerated when used in doses up to 3 grams daily. Intravenously, DHA seems to be well tolerated.
Most Common Adverse Effects:
Orally: Belching, fishy aftertaste, loose stools, and nausea.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with high doses of fish oil containing DHA.

Cardiovascular ...Orally, DHA might increase low-density lipoprotein (LDL) cholesterol levels. However, this appears to be primarily due to increases in the large buoyant type of LDL particles. The small, dense type of LDL particles are reduced (6143,48013,48078,48083,48174,48338).

Dermatologic ...Orally, DHA has been associated with one report of rash and one report of warmth on hands in one clinical study (48217). In another clinical study, two patients taking DHA 400 mg daily reported acne (11333). In another clinical study, one parent of a pediatric patient treated with DHA 600 mg daily reported increased hair loss beginning 6 weeks after completion of supplementation (90699). It is unclear if this adverse effect is specifically related to DHA intake.

Gastrointestinal ...Orally, DHA may cause gastrointestinal upset, fishy aftertaste, belching, flatulence, heartburn, loose stools, anorexia, and dry mouth (10869,11333,48217,109218). There is also some evidence that increased serum levels of DHA might be associated with an increased risk for atrophic gastritis associated with Helicobacter pylori infection, but further research is needed to clarify this finding (8709).
For fish oils containing EPA and DHA, side effects can include fishy taste, belching, nausea, and loose stools (1009,1313,8699,10007). Three people with pre-existing familial adenomatous polyposis were diagnosed with malignant lesions during the course of long-term fish oil use (999).

Genitourinary ...Orally, one patient in one clinical study who was taking DHA 1, 2, or 4 grams daily (specific dose unclear) reported decreased libido (48217).

Hematologic ...Orally, DHA might cause nose bleeds, but this is uncommon. Onset of severe nose bleeds has been reported in one clinical study in one child who took DHA 600 mg daily (98542). Although most clinical research shows that DHA does not affect blood clotting when taken alone (11112,11113,48020), there is some concern that taking high doses of oils providing DHA along with eicosapentaenoic acid (EPA) might decrease blood coagulation and increase the risk of bleeding (1313). The US Food and Drug Administration (FDA) recommends that consumers limit intake of EPA plus DHA to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).

Neurologic/CNS ...Orally, DHA may cause dizziness, headache, insomnia, fatigue, and anxiety (10869,11333,48217). In one clinical study, one parent of a pediatric patient treated with DHA 600 mg daily reported increased disruptive behavior in the child (90699).

Ocular/Otic ...Orally, DHA may cause watery eyes but results are inconsistent. In one clinical study, five of 167 infants fed formula containing 0.32% or 0.64% DHA experienced watery eyes. However, none of the infants fed formula containing 0.96% DHA experienced watery eyes (90670). In one clinical study, one patient taking DHA 400 mg daily experienced an ear infection. It is unclear if this event was related to DHA supplementation.

Oncologic ...Orally, DHA may increase the risk of prostate cancer, but additional research is needed to clarify this finding. A meta-analysis of data from observational studies found that higher dietary intake of DHA is associated with a non-linear increased risk of prostate cancer (90677). It is unclear if supplemental DHA intake is associated with increased risk of prostate cancer.

Pulmonary/Respiratory ...Orally, worsened asthma symptoms were reported by one parent of one patient with asthma taking DHA 600 mg daily (90699).

EICOSAPENTAENOIC ACID (EPA) (Eicosapentaenoic Acid)

General ...Orally, prescription EPA or EPA derived from fish oil is generally well tolerated in doses of up to 3 grams daily. Agal oil providing EPA seems to be well tolerated. Doses of EPA greater than 3 grams daily are possibly unsafe.
Intravenously, fish oil or omega-3 fatty acid lipid emulsions containing EPA seem to be well tolerated.
Most Common Adverse Effects:
Orally: Belching, diarrhea, epigastric discomfort, fishy aftertaste, and nausea.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with high doses.

Cardiovascular ...Orally, taking the prescription ethyl-EPA product (Vascepa, Amarin) 4 grams daily has been linked to a 1% greater risk of atrial fibrillation or atrial flutter that required hospitalization when compared with placebo (101286).

Dermatologic ...Orally, reported side effects of EPA have included skin rash and itching (15497).

Gastrointestinal ...Orally, reported side effects of EPA have included nausea, diarrhea, and epigastric discomfort (15497,103314,110365,110366). For fish oils containing EPA and docosahexaenoic acid, side effects can include fishy taste, belching, nausea, and loose stools (10007).

Hematologic ...Orally, reported side effects of EPA, as well as fish oils containing EPA and docosahexaenoic acid (DHA), have included nosebleed (10007,15497). There is some concern that taking high doses of oils providing EPA along with DHA might decrease blood coagulation and increase the risk of bleeding (1313). To reduce this risk, the US Food and Drug Administration (FDA) recommends that consumers limit intake of EPA plus DHA to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739). The prescription ethyl-EPA product (Vascepa, Amarin) 4 grams daily has been linked to bleeding in 12% of patients, compared with 10% in the placebo group. Serious bleeding occurred in 3% of the Vascepa group compared to 2% in the placebo group (101286).

Immunologic ...There is preliminary evidence that the EPA in fish oil decreases natural killer (NK) cell activity. Due to this effect, there is concern that increased intake of EPA might have some adverse immunologic effects and possibly increase the risk for viral infections and some cancers (8718).

Musculoskeletal ...Orally, EPA may cause musculoskeletal pain in some patients, although results from clinical research are conflicting. In one clinical study, a higher percentage of patients treated with ethyl-EPA 2 or 4 grams daily experienced joint pain compared to placebo (3.4% and 1.7% vs 0.4%, respectively) (91409). However, in another study, slightly fewer patients taking ethyl-EPA 1.8 grams daily experienced joint, lumbar, or muscle pain compared to placebo (1.6% vs 2.0%, respectively) (15497).

Oncologic ...Three people with pre-existing familial adenomatous polyposis have been diagnosed with malignant lesions during the course of long-term high-docosahexaenoic acid fish oil use (999); however, it is unclear if fish oil, or more specifically EPA, was the cause.

HUPERZINE A

General ...Orally, huperzine A seems to be well tolerated. There is currently a limited amount of information about the tolerability of intramuscular huperzine A.
Most Common Adverse Effects:
All ROAs: Huperzine A can cause dose-dependent cholinergic side effects such as blurred vision, constipation, diarrhea, dizziness, dry mouth, insomnia, nausea, sweating, and vomiting.

Cardiovascular ...Orally, huperzine A might cause decreased heart rate (3138,93482). There are two cases reported where consumption of a tea mistakenly brewed from Lycopodium selago, a source of huperzine A, has resulted in significant cholinergic toxicity, including hypertension (13193).

Gastrointestinal ...Orally, huperzine A can cause cholinergic side effects such as nausea, vomiting, diarrhea, and anorexia (93480,93481,93482,93483). Constipation and thirst have also been reported (93482,93483). In two case reports, consumption of a tea mistakenly brewed from Lycopodium selago, a source of huperzine A, has resulted in significant cholinergic toxicity, including vomiting and diarrhea (13193).

Musculoskeletal ...In two case reports, consumption of a tea mistakenly brewed from Lycopodium selago, a source of huperzine A, has resulted in significant cholinergic toxicity, including leg cramps (13193).

Neurologic/CNS ...Orally, huperzine A can cause cholinergic side effects such as dizziness (3140,55613,93481,93482) and sweating (93482). Huperzine A can also cause hyperactivity and insomnia (3138,3140,55613,93482). Fainting has also been reported (4624). In two case reports, consumption of a tea mistakenly brewed from Lycopodium selago, a source of huperzine A, has resulted in significant cholinergic toxicity, including sweating and slurred speech (13193).

General ...Phosphatidylcholine is generally well tolerated when used orally, subcutaneously, or topically.
Most Common Adverse Effects:
Orally: Altered taste, bloating, diarrhea, itching, nausea, sweating, vomiting.
Subcutaneously: Bruising, burning, edema, erythema, hematoma, itching, pain at the injection site.
Serious Adverse Effects (Rare):
Subcutaneously: Lipoma.

Dermatologic ...When taken orally, phosphatidylcholine may increase sweating (5229) and itching (63244). When given subcutaneously, phosphatidylcholine can cause pain, burning, itching, tenderness to touch, bruising, edema, and erythema at the injection site. The pain, itching and erythema usually resolve within 2 days of treatment; however localized tenderness can last longer (15623,15624,15626,15627,15628). Edema and bruising usually resolve within 10 days of treatment (15621,15623,15625). Some people can also develop nodules or hematoma at the injection site. This usually resolves within 30 days (15627).

Gastrointestinal ...Ingesting large amounts of phosphatidylcholine (30 grams per day) can cause gastrointestinal upset and diarrhea (5223). However, bloating, diarrhea, altered taste, nausea, and vomiting have been reported with smaller doses (63244,68843,93389,93390,105728). Although moderate subcutaneous doses do not usually cause systemic side effects, high doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624).

Musculoskeletal ...Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissue changes (15622).

General ...Orally and topically, turmeric is generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, dyspepsia, diarrhea, distension, gastroesophageal reflux, nausea, and vomiting.
Topically: Curcumin, a constituent of turmeric, can cause contact urticaria and pruritus.

Cardiovascular ...Orally, a higher dose of turmeric in combination with other ingredients has been linked to atrioventricular heart block in one case report. It is unclear if turmeric caused this adverse event or if other ingredients or a contaminant were the cause. The patient had taken a combination supplement containing turmeric 1500-2250 mg, black soybean 600-900 mg, mulberry leaves, garlic, and arrowroot each about 300-450 mg, twice daily for one month before experiencing atrioventricular heart block. Heart rhythm normalized three days after discontinuation of the product. Re-administration of the product resulted in the same adverse effect (17720).

Dermatologic ...Following occupational and/or topical exposure, turmeric or its constituents curcumin, tetrahydrocurcumin, or turmeric oil, can cause allergic contact dermatitis (11146,79270,79470,79934,81410,81195). Topically, curcumin can also cause rash or contact urticaria (79985,97432,112117). In one case, a 60-year-old female, with no prior reactivity to regular oral consumption of turmeric products, developed urticaria after topical application of turmeric massage oil (97432). A case of pruritus has been reported following topical application of curcumin ointment to the scalp for the treatment of melanoma (11148). Yellow discoloration of the skin has been reported rarely in clinical research (113356). Orally, curcumin may cause pruritus, but this appears to be relatively uncommon (81163,97427,104148). Pitting edema may also occur following oral intake of turmeric extract, but the frequency of this adverse event is less common with turmeric than with ibuprofen (89720). A combination of curcumin plus fluoxetine may cause photosensitivity (89728).

Gastrointestinal ...Orally, turmeric can cause gastrointestinal adverse effects (107110,107112,112118), including constipation (81149,81163,96135,113355), flatulence and yellow, hard stools (81106,96135), nausea and vomiting (10453,17952,89720,89728,96127,96131,96135,97430,112117,112118), diarrhea or loose stool (10453,17952,18204,89720,96135,110223,112117,112118), dyspepsia (17952,89720,89721,96161,112118), gastritis (89728), distension and gastroesophageal reflux disease (18204,89720), abdominal fullness and pain (81036,89720,96161,97430), epigastric burning (81444), and tongue staining (89723).

Hepatic ...Orally, turmeric has been associated with liver damage, including non-infectious hepatitis, cholestasis, and hepatocellular liver injury. There have been at least 70 reports of liver damage associated with taking turmeric supplements for at least 2 weeks and for up to 14 months. Most cases of liver damage resolved upon discontinuation of the turmeric supplement. Sometimes, turmeric was used concomitantly with other supplements and medications (99304,102346,103094,103631,103633,103634,107122,109288,110221). The Drug-Induced Liver Injury Network (DILIN) has identified 10 cases of liver injury which were considered to be either definitely, highly likely, or probably associated with turmeric; none of these cases were associated with the use of turmeric in combination with other potentially hepatotoxic supplements. Most patients (90%) presented with hepatocellular pattern of liver injury. The median age of these case reports was 56 years and 90% identified as White. In these case reports, the carrier frequency on HLAB*35:01 was 70%, which is higher than the carrier frequency found in the general population. Of the ten patients, 5 were hospitalized and 1 died from liver injury (109288).
It is not clear if concomitant use with other supplements or medications contributes to the risk for liver damage. Many case reports did not report turmeric formulation, dosing, or duration of use (99304,103094,103631,103634,109288). However, at least 10 cases involved high doses of curcumin (250-1812.5 mg daily) and the use of highly bioavailable formulations such as phytosomal curcumin and formulations containing piperine (102346,103633,107122,109288,110221).

Neurologic/CNS ...Orally, the turmeric constituent curcumin can cause vertigo, but this effect seems to be uncommon (81163).

Psychiatric ...Orally, the turmeric constituent curcumin or a combination of curcumin and fluoxetine can cause giddiness, although this event seems to be uncommon (81206,89728).

Renal ...Orally, turmeric has been linked to one report of kidney failure, although the role of turmeric in this case is unclear. A 69-year-old male developed kidney failure related to calcium oxalate deposits in the renal tubules following supplementation with turmeric 2 grams daily for 2 years as an anti-inflammatory for pelvic pain. While turmeric is a source of dietary oxalates, pre-existing health conditions and/or chronic use of antibiotics may have contributed to the course of disease (113343).

Other ...There is a single case report of death associated with intravenous use of turmeric. However, analysis of the treatment vial suggests that the vial contained only 0.023% of the amount of curcumin listed on the label. Also, the vial had been diluted in a solution of ungraded polyethylene glycol (PEG) 40 castor oil that was contaminated with 1.25% diethylene glycol. Therefore the cause of death is unknown but is unlikely to be related to the turmeric (96136).

Report an Adverse Reaction to Omega Memory with Curcumin