TruAge Extra by Morinda

POSSIBLY INEFFECTIVE

• Hypertension. Most clinical research suggests that consuming freeze-dried blueberries or blueberry powder does not lower blood pressure in patients with hypertension, prehypertension, or other risk factors for cardiovascular disease. Details: Although conflicting results exist (92386,99139), a meta-analysis of 6 clinical trials including approximately 200 patients with hypertension, prehypertension, or other risk factors for cardiovascular disease shows that consuming freeze dried blueberries or blueberry powder 22-50 grams daily for 6-8 weeks does not significantly lower systolic or diastolic blood pressure when compared with placebo (92390).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. It is unclear if oral blueberry can improve symptoms of anxiety. Details: A small clinical study in healthy adults shows that drinking 30 mL of blueberry juice diluted in 100 mL of water twice daily for 20 days reduces measures of state and trait anxiety when compared with placebo (111235).
• Age-related cognitive decline. Small clinical studies suggest that oral blueberry products may slightly improve some measures of cognitive function in older adults with age-related cognitive decline. Details: Most clinical evidence shows that blueberry can improve some aspects of cognitive decline, but it has minimal effect on other measures. One small clinical trial in older patients with self-reported cognitive decline shows that taking freeze-dried blueberry powder 12.5 grams twice daily for 6 months modestly improves cognitive performance in daily activities but most measures of cognitive function did not improve (97181). Another small clinical study in patients 60 years of age and older with self-reported memory complaints shows that taking a wild blueberry extract (ThinkBlue, Naturex Inc) 100 mg daily with cysteine and glutathione modestly improves episodic memory at 3 months, but not at 6 months, when compared with placebo. However, taking this same blueberry extract or a wild blueberry powder 450 mg or 900 mg daily with cysteine and glutathione does not improve sequence recall, working memory, or executive function (99139). Other small clinical studies show a benefit in some, but not all measures of executive functioning and memory (96467,111234)
• Aging. It is unclear if consuming blueberry can improve functional mobility in adults 60 years of age and older. Details: One small clinical study in adults over 60 years of age shows that consuming 2 cups of frozen blueberries daily for 6 weeks improves some measures of functional mobility, such as foot placement and balance, when compared with drinking carrot juice. However, blueberry does not seem to improve hand grip strength, executive function, or other measurements of gait speed when compared with carrot juice (92387). Another small clinical study in this same age group shows that consuming 12 grams of powdered blueberry mixed with liquid twice daily for 3 months does not improve measures of functional mobility when compared with placebo (96467).
• Athletic performance. Small clinical studies suggest that oral freeze-dried blueberry powder may not reduce exertion or improve long-distance running performance in trained runners. Details: Two small clinical studies in adults with running experience show that taking freeze-dried blueberry powder 24 grams three times daily for four days does not improve perceived exertion, the time to run 8 km, or distance run over 30 minutes when compared with placebo. However, blueberry does appear to modestly attenuate increases in blood lactate after running (101963,107282).
• Cancer. Although there has been interest in using oral blueberry for preventing cancer, there is insufficient reliable information about the clinical effects of blueberry for this purpose.
• Cardiovascular disease (CVD). Small clinical studies suggest that oral blueberry supplementation might modestly improve body weight and triglyceride levels, but not body mass index (BMI), glycemic control, or cholesterol levels, in patients at risk for CVD. Details: A meta-analysis of 11 small and low-quality clinical studies involving a total of 497 adults with various risk factors for CVD shows that taking blueberry for 4-16 weeks modestly reduces weight and triglyceride levels, but does not improve other risk factors for CVD, including BMI, glycemic indices, cholesterol levels, and certain inflammatory mediators, when compared with placebo or other control. In a sub-group analysis, weight reduction was slightly more favorable in studies of longer than 6 weeks' duration (mean reduction of 0.91 kg) and in studies using blueberry powder or freeze-dried blueberry (mean reduction of 0.86 kg) (105702). The validity of these findings is limited by the heterogeneity and small size of the included studies. Additionally, it is unclear if blueberry is beneficial for reducing the risk for CVD or CVD-related complications.
• Cataracts. Although there has been interest in using oral blueberry for preventing cataracts, there is insufficient reliable information about the clinical effects of blueberry for this purpose.
• Cognitive function. Small clinical studies suggest that oral blueberry products may improve some, but not most, measures of cognitive function in children and adults. Details: Several small clinical studies in children 7-10 years of age show that drinking a blueberry drink containing 30 grams of freeze-dried blueberries or 200 grams of fresh blueberries as a single dose does not improve most measures of cognitive function when compared with placebo. These trials showed small improvements in some measures of cognitive function, including auditory-verbal learning, word recognition, and delayed memory, but these specific findings were not consistent across all studies (92394,96465,101961). Additionally, a small clinical trial in healthy young adults shows that taking a combination of blueberry and grape extracts (Memophenol, Activ'Inside) 600 mg increases the ability to complete serial three subtraction by 2.5-fold when compared with placebo. However, there were no other improvements in working memory or attention during a sustained cognitive effort (101960).
• Depression. It is unclear if oral blueberry extract or freeze-dried powder is beneficial in patients with depression. Details: One small clinical study in adults with cerebral venous thrombosis (CVT)-associated depression and depression-associated gastrointestinal infection shows that taking blueberry extract 10 mg daily for 3 months reduces symptoms of depression by 49% and gastrointestinal infection rates by 84% when compared to baseline; when compared with placebo, these changes are significant (96464). Another small clinical study in healthy adults shows that drinking 30 mL of blueberry juice diluted in 100 mL of water twice daily for 20 days reduces symptoms of depression when compared with placebo (111235). A small clinical study in healthy adolescents 11-17 years of age without diagnosed mental health issues at baseline shows that drinking freeze-dried wild blueberry powder 13 grams daily for 4 weeks improves self-reported depressive symptoms, but not anxiety symptoms or transient affect, when compared with placebo. The adolescents enrolled in this study were found to have suboptimal fruit and vegetable intake at baseline (105703).
• Diabetes. It is unclear if oral freeze-dried blueberry powder is beneficial in patients with diabetes. Details: A small clinical study in males 45-75 years of age with type 2 diabetes shows that drinking 11 grams of freeze-dried highbush blueberry powder mixed with water twice daily with a meal for 8 weeks reduces glycated hemoglobin (HbA1c) values and triglyceride levels, but not body weight, fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, or blood pressure, when compared with placebo. This study may have been inadequately powered to detect a difference between groups (105701). Blueberry has also been evaluated for the prevention of gestational diabetes. A small clinical study in patients with a history of gestational diabetes shows that consuming 280 grams of blueberries plus 12 grams of soluble fiber daily for 18 weeks, starting at less than 20 weeks' gestation, along with standard care reduces maternal weight gain and blood glucose levels after glucose challenge testing when compared with standard care alone. However, neither gestational diabetes incidence nor infant birth weight was lower with blueberry supplementation when compared with standard care alone (107281).
• Hyperlipidemia. It is unclear if oral blueberry is beneficial in patients with hyperlipidemia. Details: One small clinical study in healthy adults shows that drinking blueberry juice 30 mL twice daily for 20 days reduces total cholesterol and low-density lipoprotein (LDL) cholesterol when compared with placebo (111235). Additionally, drinking a combination of blueberry, apple, chokeberry, and cranberry juice 300 mL daily for 6 weeks appears to decrease total cholesterol and increase high-density lipoprotein (HDL) cholesterol when compared to baseline in females with overweight or obesity and at least one risk factor for cardiovascular disease (111233). However, the validity of the study is limited by its small size, short duration, and lack of a comparator group. It is unclear if these effects are due to blueberry, other ingredients, or the combination. In contrast, other small clinical studies suggest that blueberry does not improve lipid levels (105701,111234). A small clinical study in males 45-75 years old shows that blueberry has no effect on total cholesterol, HDL cholesterol, and LDL cholesterol, but may reduce triglycerides, when compared with placebo. However, in a sub-group of patients also taking lipid-lowering medications, blueberry reduced levels of total cholesterol and LDL cholesterol when compared with placebo (105701). Another small clinical study in middle-aged adults with overweight shows that taking oral blueberry powder daily for 12 weeks does not impact total cholesterol, LDL cholesterol, HDL cholesterol, or triglycerides when compared with placebo (111234). However, these studies may have been inadequately powered to detect a difference between groups.
• Hypertriglyceridemia. It is unclear if oral blueberry leaf extract is beneficial in patients with hypertriglyceridemia. Details: A small clinical trial in patients with mild to moderate hypertriglyceridemia shows that taking a single dose of a blueberry leaf extract 300 mg along with a high-fat meal reduces postprandial triglyceride levels, but not postprandial glucose or insulin levels, when compared with placebo (101959).
• Juvenile idiopathic arthritis (JIA). It is unclear if oral blueberry juice is beneficial in children with JIA. Details: A small clinical study in children with JIA shows that adding 50 mL of blueberry juice daily to treatment with etanercept 50 mg twice weekly for 6 months increases the percentage of patients who achieve a 20% improvement in symptoms based on American College of Rheumatology criteria when compared with taking etanercept along with placebo juice. About 75% of patients in the blueberry juice group experienced a 20% improvement in symptoms, compared with 51% of patients in the placebo group, suggesting that for every four patients that drink blueberry juice along with etanercept therapy, one additional patient will experience a 20% or greater improvement in symptoms. Drinking blueberry juice also appears to reduce side effects caused by etanercept, including weight gain, infection, diarrhea, and anorexia (92388).
• Metabolic syndrome. Small clinical studies in patients with metabolic syndrome, along with an analysis of studies in patients at risk for metabolic syndrome, suggest that oral freeze-dried blueberries do not improve body weight or glycemic control, but may slightly lower blood pressure and cholesterol levels. Details: A small clinical study in patients with metabolic syndrome shows that taking freeze-dried blueberry powder 26 grams daily for 6 months improves flow-mediated dilation by 45% when compared with placebo, but does not affect low-density lipoprotein (LDL) cholesterol levels, insulin resistance, or blood pressure. In a sub-group of patients not taking statins, blueberry increased levels of high-density lipoprotein (HDL) cholesterol by 3 mg/dL; however, a lower dose of 13 grams daily had no beneficial effects (101958). Another small clinical trial in patients with metabolic syndrome shows that consuming freeze-dried blueberries 25 grams twice daily for 8 weeks reduces systolic blood pressure by around 4% and diastolic blood pressure by around 3% when compared with placebo, but does not affect body weight, lipid levels, or glycemic control (107278). Additionally, a small clinical trial in patients with metabolic syndrome shows that drinking a smoothie containing freeze-dried blueberry powder 22.5 grams twice daily for 6 weeks does not improve blood pressure, body weight, glycemic control, or lipid levels when compared with placebo, although it does improve measures of endothelial function (107279). A meta-analysis evaluating the studies above, along with 9 small clinical trials in patients at risk for metabolic syndrome, shows that blueberry supplementation does not improve body weight, glycemic control, triglyceride levels, or systolic blood pressure. However, it reduces total cholesterol by around 8 mg/dL, low-density lipoprotein (LDL) cholesterol by around 9 mg/dL, and diastolic blood pressure by around 2 mmHg when compared with placebo (107280).
• Muscle strength. Oral blueberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in young, healthy males shows that taking blueberry extract 200 mg plus phosphocreatine disodium salts 5 grams daily for 28 days improves peak torque and average power during leg extension exercises when compared to baseline, while individuals taking placebo saw no improvements in these measures (107284). It is unclear if these findings are due to blueberry, phosphocreatine, or the combination.
• Night vision. Although there has been interest in using oral blueberry for improving night vision, there is insufficient reliable information about the clinical effects of blueberry for this purpose.
• Obesity. Oral blueberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with overweight or obesity and at least one risk factor for cardiovascular disease shows that drinking a combination of blueberry, apple, chokeberry, and cranberry juice 300 mL daily for 6 weeks does not reduce body weight, body mass index (BMI), or blood pressure but might improve total cholesterol and high-density lipoprotein (HDL) cholesterol when compared to baseline (111233). However, the validity of these findings is limited by the small study size, short duration, and lack of a comparator group. It is unclear if these effects are due to blueberry, other ingredients, or the combination.
• Urinary tract infections (UTIs). Although there has been interest in using oral blueberry for preventing UTIs, there is insufficient reliable information about the clinical effects of blueberry for this purpose. More evidence is needed to rate blueberry for these uses.

(Read more about BLUEBERRY)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral noni for aging, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Asthma. Although there has been interest in using oral noni for asthma, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Atherosclerosis. Although there has been interest in using oral noni for atherosclerosis, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Athletic performance. It is unclear if oral noni juice is beneficial for athletic performance. Details: Preliminary clinical research shows that drinking 100 mL of a specific juice (Tahitian Noni Juice (TNJ), Tahitian Noni International) containing 89% pureed noni in grapefruit and blackberry juices twice daily for 21 days can increase running time-to-fatigue by approximately 21% in trained distance runners when compared with baseline. Runners taking placebo blackberry juice did not demonstrate improved endurance when compared with baseline (65230).
• Burns. Although there has been interest in using topical noni for burns, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Cancer. It is unclear if oral noni is beneficial in patients with cancer. Details: Preliminary, low-quality clinical research shows that taking noni fruit extract 2-14 grams daily for 28 days does not improve physical function, fatigue, pain, or tumor growth in patients with various forms of advanced cancer when compared with baseline (65173).
• Cardiovascular disease (CVD). Although there has been interest in using oral noni for CVD, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Cataracts. Although there has been interest in using oral noni for cataracts, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Cervical spondylosis. It is unclear if oral noni is beneficial in patients with cervical spondylosis. Details: Preliminary clinical research shows that taking oral noni juice 15 mL twice daily in combination with physiotherapy for 4 weeks can improve neck pain and flexibility scores more than physiotherapy alone in patients with cervical spondylosis. Treatment with noni juice alone was not different than physiotherapy alone. However, the study may have been inadequately powered to detect a difference between these groups (65197).
• Colic. Although there has been interest in using oral noni for colic, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Common cold. Although there has been interest in using oral noni for the common cold, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Cough. Although there has been interest in using oral noni for cough, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Depression. Although there has been interest in using oral noni for depression, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Diabetes. Although there has been interest in using oral noni for diabetes, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Epilepsy. Although there has been interest in using oral noni for epilepsy, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Headache. Although there has been interest in using oral and topical noni for headache, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Hearing loss. It is unclear if oral noni is beneficial for hearing loss. Details: Preliminary clinical research shows that drinking 4 ounces of noni juice daily for 3 months does not improve hearing at most frequencies in hearing-impaired postmenopausal females (65146).
• HIV/AIDS. Although there has been interest in using oral noni for HIV/AIDS, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Hypertension. It is unclear if oral noni is beneficial in patients with hypertension. Details: Preliminary clinical research shows that drinking 4 ounces of a specific noni juice (Tahitian Noni Juice) daily for one month reduces blood pressure by approximately 8% when compared with baseline in individuals with hypertension (65231). The validity of this finding is limited by the lack of a comparator group.
• Insomnia. Although there has been interest in using oral noni for insomnia, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Leishmania lesions. It is unclear if topical noni is beneficial for improving the severity of leishmania lesions. Details: Preliminary clinical research shows that topical application of an ointment containing noni stem extract 1% three times daily for 6 weeks improves leishmania lesion scores when compared with baseline. A good to excellent response was reported in 80% of patients (65174). However, the validity of this finding is limited by the lack of a comparator group.
• Leprosy. Although there has been interest in using topical noni for leprosy, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Liver disease. Although there has been interest in using oral noni for liver disease, there is insufficient reliable information about the clinical effects of noni for this purpose. Additionally, there is some concern that noni might cause hepatotoxicity in some patients.
• Malaria. Although there has been interest in using oral noni for malaria, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Migraine headache. Although there has been interest in using oral noni for migraine headache, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Osteoarthritis. It is unclear if oral noni is beneficial in patients with osteoarthritis. Details: Preliminary clinical research in patients with knee or hip osteoarthritis shows that drinking 3 ounces of a specific noni juice (Tahitian Noni Juice) daily for 90 days can reduce the need for analgesic medications and improve quality of life parameters, including mobility, joint function, social activity, tension level, mood, and the ability to conduct activities of daily living when compared with baseline (65206). However, the validity of this study is limited by the lack of a comparator group.
• Parturition. Although there has been interest in using oral noni for parturition, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Postoperative nausea and vomiting (PONV). It is unclear if oral noni is beneficial in patients with PONV. Details: Preliminary clinical research shows that taking noni fruit extract 600 mg orally one hour prior to surgery reduces postoperative nausea, but not vomiting, in the first 6 hours after surgery by 40% when compared with placebo. However, taking noni fruit extract did not reduce PONV in the first 6-24 hours after the surgery. Taking noni fruit extract 150-300 mg also did not reduce PONV when compared with placebo (17169).
• Premenstrual syndrome (PMS). Although there has been interest in using oral noni for PMS, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral and topical noni for RA, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Stroke. Although there has been interest in using oral noni for stroke, there is insufficient reliable information about the clinical effects of noni for this purpose.
• Urinary tract infections (UTIs). Oral noni has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some observational research in females with recurrent UTIs has found that taking antibiotics with a combination of noni fruit extract 200 mg, d-mannose 500 mg, and N-acetylcysteine 100 mg orally twice daily for 2 months, then daily for 4 months, may be associated with a lower incidence of recurrent UTI when compared with antibiotics alone. Of patients without a UTI in the first 2 months, 100% of those taking the combination product remained UTI free at 6 months whereas only 6% of those taking antibiotics alone remained UTI free. This combination also seems to improve symptoms of urgency, frequency, and incontinence (97360). It is not clear if these effects are due to noni, other ingredients, or the combination.
• Wound healing. Although there has been interest in using topical noni for wound healing, there is insufficient reliable information about the clinical effects of noni for this purpose. More evidence is needed to rate noni for these uses.

(Read more about NONI)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dyspepsia. Oral olive leaf extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in healthy adults shows that taking a specific combination product containing olive leaf extract 24% and prickly pear cactus 33% (Mucosave, Bionap S.R.L.) 400 mg daily for 8 weeks seems to improve dyspepsia and other gastrointestinal symptoms when compared with placebo (105904). It is unclear if this benefit would occur in patients with clinically diagnosed dyspepsia.
• Exercise-induced respiratory infections. It is unclear if oral olive leaf extract is beneficial for reducing respiratory infections from exercise. Details: A small clinical study in high school athletes shows that taking one tablet of olive leaf extract providing eleuropein 100 mg daily for 2 months during training season does not reduce the incidence of the common cold when compared with placebo. While it may reduce the number of sick days by 28%, a sub-group analysis suggests that this reduction is only evident in female athletes (101860).
• Gastroesophageal reflux disease (GERD). Although there is interest in using oral olive leaf for GERD, there is insufficient reliable information about the clinical effects of olive for this condition.
• Herpes zoster (shingles). Although there is interest in using oral olive leaf for shingles, there is insufficient reliable information about the clinical effects of olive for this condition.
• Influenza. Although there is interest in using oral olive leaf for influenza, there is insufficient reliable information about the clinical effects of olive for this condition.
• Metabolic syndrome. It is unclear if oral olive leaf extract is beneficial for improving body composition and cardiovascular risk factors in patients with metabolic syndrome. Details: A small clinical trial in overweight, middle-aged males at risk for metabolic syndrome shows that taking four capsules of olive leaf extract providing oleuropein 51.1 mg and hydroxytyrosol 9.7 mg daily for 12 weeks improves insulin sensitivity by 15% when compared with placebo. However, body composition, blood pressure, cholesterol levels, and other cardiovascular risk factors were not improved (92245).
• Osteoarthritis. It is unclear if oral olive fruit or leaf extract is beneficial for improving osteoarthritis. Details: Preliminary clinical research shows that taking a freeze-dried aqueous extract of olive fruit 400 mg daily for 8 weeks decreases pain and increases mobility in people with osteoarthritis (14844). Other preliminary clinical research in adults with knee osteoarthritis shows that taking olive leaf extract 50.1 mg daily for 4 weeks improves overall pain measurements by 14%, compared to only 4% in the placebo group. However, many individual measurements of pain are not improved (92252).
• Osteoporosis. It is unclear if oral olive leaf extract is beneficial for osteoporosis. Details: Clinical research shows that taking olive leaf extract (Bonolive, BioActor BV) 250 mg daily for 12 months, along with elemental calcium 400 mg daily, increases osteocalcin levels by about 32% when compared to baseline; this increase was significant when compared to those taking calcium 400 mg plus placebo, who showed a 6% decrease in osteocalcin levels. However, taking olive leaf extract does not significantly increase bone mineral density of the lumbar spine or femur neck when compared with placebo (92247).
• Rheumatoid arthritis (RA). It is unclear if oral olive fruit extract is beneficial for improving RA symptoms. Details: Preliminary clinical research in adults with RA shows that taking an aqueous freeze-dried extract of olive fruit 400 mg daily for 8 weeks does not improve symptoms when compared with control (14844). More evidence is needed to rate the effectiveness of olive for these uses.

(Read more about OLIVE)

LIKELY SAFE ...when used orally and appropriately. Blueberry, as the whole fruit, juice, or in a powder formulation, is safe when consumed in amounts commonly found in foods (13533,92387,92388,92394,96467,97181,99139). There is insufficient reliable information available about the safety of blueberry when used topically or when the leaves are used orally.

CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods (13533,96465).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (13533,107281). There is insufficient reliable information available about the safety of blueberry for medicinal use; avoid using.

(Read more about BLUEBERRY)

POSSIBLY SAFE ...when used orally and appropriately. Noni juice has been used in doses of up to 200 mL daily with apparent safely in small clinical studies for up to 3 months (11944,17169,65173). However, there have been several case reports of increased liver enzymes and hepatotoxicity in people taking some noni products (13107,14341,14468,17170,17171,17172). In three reports, hepatotoxicity was linked to a specific brand of noni juice (Tahitian Noni Juice, Tahitian Noni International) (14341,17171). It is unclear if potential contaminants or hypersensitivity reactions may be the cause of these events. More evidence is needed to determine if noni increases the risk for hepatotoxicity. There is insufficient reliable information available about the safety of noni fruit extract when used orally or the safety of noni when used topically.

PREGNANCY AND LACTATION:
While animal research is conflicting on the teratogenic effects of noni (65205,65206), there is insufficient reliable information available about the safety of noni in humans; avoid using.

(Read more about NONI)

LIKELY SAFE ...when olive fruit is used orally and appropriately in amounts commonly found in foods.

POSSIBLY SAFE ...when olive leaf extract is used orally and appropriately. Olive leaf extract providing 51-100 mg oleuropein daily has been used with apparent safety for 6-8 weeks (92245,92247,101860). There is insufficient reliable information available about the safety of olive fruit extract when used in amounts greater than those found in foods.

PREGNANCY AND LACTATION:
Insufficient reliable information available; stick with amounts commonly found in foods.

(Read more about OLIVE)

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, blueberries or blueberry leaf extracts might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal and in vitro research suggests that blueberry and/or blueberry leaf extracts can lower blood glucose levels (909,36743,36759).

BUSPIRONE (BuSpar) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, blueberry juice might increase blood levels of buspirone.  Details In vitro research shows that blueberry juice can inhibit the metabolism of buspirone, possibly by inhibiting cytochrome P450 3A (CYP3A) enzymes. However, pharmacokinetic research in humans shows that drinking 300 mL of blueberry juice 30 minutes before taking buspirone hydrochloride 10 mg does not significantly affect the concentration or clearance of buspirone (92385).

FLURBIPROFEN (Ansaid, others) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, blueberry juice might increase blood levels of flurbiprofen.  Details In vitro research shows that blueberry juice can inhibit the metabolism of flurbiprofen, possibly by inhibiting cytochrome P450 2C9 (CYP2C9) enzymes. However, pharmacokinetic research in humans shows that drinking 300 mL of blueberry juice 30 minutes before taking flurbiprofen 100 mg does not significantly affect the concentration or clearance of flurbiprofen (92385).

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ACE INHIBITORS (ACEIs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining noni and ACE inhibitors might increase the risk of hyperkalemia.  Details Noni juice contains significant amounts of potassium, about 6 mEq/100 mL juice (1298). This may increase the risk for hyperkalemia when used in conjunction with ACE inhibitors, which can also increase potassium levels.

ANGIOTENSIN RECEPTOR BLOCKERS (ARBs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining noni and ARBs might increase the risk of hyperkalemia.  Details Noni juice contains significant amounts of potassium, about 6 mEq/100 mL juice (1298). This may increase the risk for hyperkalemia when used in conjunction with ARBs, which can also increase potassium levels.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, noni may increase the risk of hypotension when used in combination with antihypertensive drugs.  Details Preliminary clinical research suggests that drinking noni juice can reduce blood pressure in individuals with hypertension (65231).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking noni with hepatotoxic drugs might increase the risk of liver damage.  Details There is concern that noni might cause hepatotoxicity in some patients (13107,14341,14468). Advise patients against combining noni with potentially hepatotoxic drugs.

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking noni fruit juice concomitantly with phenytoin may lower phenytoin levels and increase the risk of seizures.  Details In one case report, an adult taking phenytoin for partial seizures experienced low serum phenytoin levels while taking noni juice 90-200 mL daily. Serum phenytoin levels increased after decreasing noni juice consumption; similarly, serum phenytoin levels decreased after increasing noni juice consumption. Some researchers believe noni juice may induce cytochrome P450 2C9 enzymes, which would decrease phenytoin levels, but this has not been well studied. Patients may need additional monitoring when starting or stopping noni juice supplementation (106057).

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combing noni and a potassium-sparing diuretic might increase the risk of hyperkalemia.  Details Noni juice contains significant amounts of potassium, about 6 mEq/100 mL juice (1298). This may increase the risk for hyperkalemia when used in conjunction with potassium-sparing diuretics, which can also increase potassium levels.

RANITIDINE (Zantac) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Taking noni fruit with ranitidine might increase the levels and clinical effects of ranitidine.  Details Clinical evidence shows that taking an aqueous extract of noni fruit 30 minutes prior to taking a single oral dose of ranitidine can increase the rate of absorption and plasma concentration of ranitidine (23387).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking noni juice concomitantly with warfarin might decrease the effectiveness of warfarin.  Details In one case, a 41-year-old patient stabilized on warfarin had a decreased international normalized ratio (INR) following consumption of a specific commercial noni juice product (Noni juice 4 Everything). While the patient was still taking noni juice, an increase in warfarin dose did not produce an increase in INR (14434). However, it should be noted that this particular product contained extracts and derivatives from more than 115 components, many of which contained vitamin K. Furthermore, vitamin K was listed as a separate ingredient of the product, suggesting that the product was possibly fortified with vitamin K. It has not been verified that noni fruit alone contains a significant amount of vitamin K or interacts with warfarin.

(Read more about NONI)

(Read more about OLIVE)

General ...Orally, blueberry is generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, nausea, and vomiting with freeze-dried blueberries.

Gastrointestinal ...Orally, freeze-dried blueberries may cause constipation, diarrhea, nausea, and vomiting. In one clinical trial, 26% of patients taking freeze-dried blueberries 50 grams daily dropped out in the first week of the study due to gastrointestinal complaints (107278).

(Read more about BLUEBERRY)

General ...Orally and topically, noni seems to be generally well tolerated; however, high quality studies of adverse effects have not been conducted.
Most Common Adverse Effects:
Orally: Abdominal discomfort, nausea.
Serious Adverse Effects (Rare)::
Orally: Hepatotoxicity, including liver failure. However, studies have not conclusively identified whether noni, or contaminants in noni products, were responsible for this toxicity.

Gastrointestinal ...Orally, dehydrated noni fruit has been reported to cause nausea and abdominal discomfort (65173).

Hepatic ...Noni has been associated with several cases of hepatotoxicity in previously healthy patients ranging in age from 14 to 62 years (13107,14341,14468,17170,17171,17172). In two cases, the patients had used a tea or other herbal products containing noni (13107,17172); five had consumed noni juice, specifically Tahitian Noni Juice (Tahitian Noni International) (14341,16648,17171); and two cases involved energy drinks containing several herbal ingredients including noni (17170,90125). Symptoms of liver dysfunction and elevated liver function tests (LFTs) were seen between 2 weeks and 4 months after starting noni. The LFTs started to improve within 2 days of stopping noni and generally normalized within 1 month (13107,14468,17171). Biopsy findings included acute hepatitis, inflammation, hepatocyte necrosis, and hepatocellular cholestasis (14341,17170). One patient, who had a history of prior mild acetaminophen toxicity, had rapidly progressive liver failure after noni ingestion and required transplantation (14341).
Potential product contamination was not ruled out in these case reports. Some researchers theorize that anthraquinones contained in noni could potentially cause hepatotoxicity. Other products containing anthraquinones, such as senna, have been linked to cases of hepatotoxicity. However, analyses of a noni juice product associated with reports of liver damage (Tahitian Noni Juice, Tahitian Noni International) have not detected anthraquinone content (14444). Another analysis of noni fruit puree from which the seeds and skin had been removed had no detectable anthraquinones (92201). However, products containing seed or leaf material had detectable amounts of anthraquinones (92201). The part of the noni plant used might affect hepatotoxicity risk. More evidence is needed to determine if noni causes hepatotoxicity.

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General ...Orally, olive fruit is well tolerated when used in typical food amounts. Olive leaf extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Headache and stomach discomfort.

Dermatologic ...Orally, one patient in one clinical trial reported bad skin and acne after using olive leaf extract (101860).

Gastrointestinal ...Orally, three patients in one clinical trial reported stomach ache after using olive leaf extract (101860).

Neurologic/CNS ...Orally, three patients in one clinical trial reported headache after using olive leaf extract (101860).

Psychiatric ...In one case report, a 67-year-old female experienced irritability, anger, a lack of control, and feelings of sadness and negativity after consuming a multi-ingredient product containing olive leaf extract 5 grams, horseradish root, and eyebright daily for 38 days. All psychiatric symptoms disappeared within days of stopping the combined product. It is hypothesized that the hydroxytyrosol component of olive leaf extract contributed to these symptoms due to its chemical similarity to dopamine; however, it is not clear if these symptoms were due to the olive leaf extract or to the other ingredients (96245).

Pulmonary/Respiratory ...Olive tree pollen can cause seasonal respiratory allergy (1543).

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