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Alcohol use disorder. Although there has been interest in using oral agmatine for alcohol use disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Alzheimer disease. Although there has been interest in using oral agmatine for Alzheimer disease, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Anxiety. Although there has been interest in using oral agmatine for anxiety, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Athletic performance. Although there has been interest in using oral agmatine for improving athletic performance, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Autism spectrum disorder. Although there has been interest in using oral agmatine for autism spectrum disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Bipolar disorder. Although there has been interest in using oral agmatine for bipolar disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Depression. Although there has been interest in using oral agmatine for depression, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Epilepsy. Although there has been interest in using oral agmatine for epilepsy, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Herniated disc. It is unclear if oral agmatine is beneficial in patients with herniated disc. Details: A small clinical study in patients with radicular pain associated with lumbar disc herniation shows that taking agmatine sulfate 890 mg three times daily for 14 days decreases pain scores by around 20% and increases health-related quality of life scores by around 50% when compared with placebo (94736).
Muscle strength. Although there has been interest in using oral agmatine for increasing muscle strength, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Parkinson disease. Although there has been interest in using oral agmatine for Parkinson disease, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Peripheral neuropathy. It is unclear if oral agmatine is beneficial in patients with peripheral neuropathy. Details: A small, open-label study in patients with peripheral neuropathy of mixed etiologies shows that taking a specific agmatine sulfate product (AgmaSet, Gilad&Gilad LLC) 2.67 grams daily, in divided doses, for 2 months reduces pain intensity by around 46% and improves symptom scores for burning, numbness, and tingling when compared to baseline (111144). The validity of these findings is limited by a lack of comparator group.
Schizophrenia. Although there has been interest in using oral agmatine for schizophrenia, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Stroke. Although there has been interest in using oral agmatine for neuroprotection against stroke, there is insufficient reliable information about the clinical effects of agmatine for this purpose. More evidence is needed to rate agmatine for these uses.

Hypercholesterolemia. Consuming a diet rich in avocados seems to improve serum lipid levels. Details: Consuming a diet rich in avocados (e.g., 0.5-2 avocados daily or a diet in which avocados account for 75% of total daily fat intake) for 1-4 weeks seems to lower total serum cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B. It may also increase high-density lipoprotein (HDL) serum cholesterol levels (668,669,670,671,33256). In contrast, a meta-analysis of 8 clinical studies in adults with various metabolic conditions shows that consuming avocado 99-330 grams daily for 3-24 weeks reduces total cholesterol by 5 mg/dL but does not reduce LDL cholesterol or triglycerides or increase HDL cholesterol when compared with diets containing no or low amounts of avocado. However, subgroup analysis in patients with hypercholesterolemia suggests that consuming avocado reduces LDL cholesterol by 9 mg/dL and total cholesterol by 7.5 mg/dL (112435).

Aging skin. It is unclear if consuming avocado is beneficial for aging skin. Details: A small study in females with overweight or obesity shows that consuming one avocado daily for 8 weeks improves forehead skin firmness, but not elasticity or tiring, when compared with no avocado consumption. No improvements in under eye skin firmness, elasticity, or tiring were observed (108010).
Cardiovascular disease (CVD). It is unclear if consuming avocado is beneficial for reducing the risk of CVD. Details: Observational research has found that consumption of at least one avocado weekly is associated with a 16% lower risk of CVD and a 21% lower risk of coronary heart disease (CHD) when compared with no avocado consumption. However, there was no association between avocado consumption and the risk of stroke. Additionally, replacement of half a serving daily of certain fat-containing foods (i.e., margarine, butter, egg, yogurt, cheese, processed meats) with an equivalent amount of avocado is associated with a 16% to 22% lower risk of CVD (108007).
Cognitive function. It is unclear if consuming avocados is beneficial for improving cognitive function. Details: Preliminary clinical research in adults with overweight or obesity shows that consuming one avocado daily as part of a test meal for 12 weeks improves attentional inhibition, but not response inhibition, during cognitive testing when compared with baseline. Improvements on these tests were not reported in patients receiving an isocaloric control meal (103895). A cross-sectional study in older adults has also found that avocado consumption is associated with improvements in memory performance on immediate learning and delayed recall tests as well as global cognitive scores when compared with no avocado consumption (108013).
Metabolic syndrome. It is unclear if consuming avocados is beneficial for metabolic syndrome. Details: A very large clinical study in adults with an elevated waist circumference shows that consuming a large avocado daily for 6 months reduces total cholesterol by 3 mg/dL and low-density lipoprotein cholesterol by 2.5 mg/dL but does not change any other measures of metabolic syndrome including visceral adiposity, waist circumference, body weight, body mass index (BMI), systolic and diastolic blood pressure, glucose, insulin, triglycerides, very low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol when compared with a standard diet without avocados (112436). Additionally, a small clinical study in adults with overweight, obesity, and insulin resistance shows that consuming an avocado daily for 12 weeks does not change BMI, body composition, blood pressure, fasting glycemic indices, glucose levels, plasma lipid profiles, insulin sensitivity, or markers of inflammation or endothelial function when compared with control (112438).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if consuming avocados is beneficial for NAFLD. Details: A secondary analysis of a previous clinical study in adults with overweight and obesity shows that consuming 14 avocados per week per family for 6 months does not improve NAFLD fibrosis score or biomarkers of hepatic function including alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl-transferase (GGT), or high-sensitivity c-reactive protein (hsCRP) when compared with low avocado consumption, defined as 3 avocados per week per family (112437).
Obesity. It is unclear if consuming avocados is beneficial for weight loss or prevention of weight gain. Details: A meta-analysis of clinical trials and a very large clinical study in adults with overweight, obesity, and elevated waist circumference shows that consuming one avocado daily or 136-200 grams daily for 6 weeks to 6 months does not reduce body weight, body mass index (BMI), percent fat mass, or visceral adipose tissue when compared with control (112433,112436). However, a small study in adults with overweight or obesity shows that consuming one avocado daily for 12 weeks changes abdominal adiposity distribution among females, but not males, when compared with no avocado consumption. No significant effects were observed for glucose or insulin outcomes (108008). Preliminary clinical research in adults with overweight or obesity shows that eating half of an avocado with lunch increases satisfaction by 23% to 26% and decreases desire to eat by 28% to 40% when compared with a control lunch with no avocado (93109). A large observational study in the same population has found that habitual consumption of avocado at an average intake of 32 grams or more daily is not associated with reductions in body weight or body mass index (BMI) over 5 years when compared with no avocado consumption. Additionally, this study suggests that while habitual avocado consumption in patients with normal weight may slightly attenuate increases in body weight and BMI, it does not seem to reduce the odds of these patients becoming overweight or developing obesity over time when compared with no avocado intake (100936).
Psoriasis. Topical avocado has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with psoriasis shows that applying a specific cream containing avocado oil and vitamin B12 (Regividerm, Regeneratio Pharma AG) 0.7 mg/gram to the affected area for 12 weeks reduces symptoms to a similar extent when compared with calcipotriol ointment (Psorcutan). The avocado combination cream also causes significantly less irritation than calcipotriol (14909). It is unclear if these effects are due to avocado, vitamin B12, or the combination. More evidence is needed to rate avocado for these uses.

BRANCHED-CHAIN AMINO ACIDS (BCAA) (Glycyl-Alanyl-Lysine-L-Leucine, Glycyl-Alanyl-Lysine-L-Isoleucine, Glycyl-Alanyl-Lysine-L-Valine)

Hepatic encephalopathy. Oral and intravenous BCAAs improve symptoms and nutritional status in patients with hepatic encephalopathy, especially in those not tolerating protein supplementation. Details: Taking BCAAs 240 mg/kg (up to 25 grams) daily in 3 divided doses for up to 3 months can improve symptoms, liver function tests, and nitrogen balance in patients with chronic hepatic encephalopathy (68,69,82,690,92643,97531). Oral BCAAs are recommended for malnourished patients with chronic hepatic encephalopathy who cannot tolerate protein supplementation (69,4274). When the enteral route is unavailable and when patients cannot tolerate general purpose amino acid solutions, intravenous solutions with BCAAs can be used for nutritional support; however, most patients can tolerate standard amino acid mixtures (4274). Some clinical research also suggests that taking BCAAs orally improves psychomotor function, attention, intelligence, and driving ability in patients with latent hepatic encephalopathy (684,685,37131,97531). However, not all studies show a positive effect of BCAAs on psychometric outcomes (37135). There is also some preliminary evidence that intravenous BCAAs might be helpful for reversing coma in acute hepatic encephalopathy, although findings are conflicting (66,81,686,687,688,689,4274,37134). BCAAs do not appear to reduce the risk of mortality or improve quality of life in patients with hepatic encephalopathy (92643,97531).
Tardive dyskinesia. Oral BCAAs might reduce symptoms of tardive dyskinesia precipitated by antipsychotic drugs. Details: Taking BCAAs orally seems to reduce symptoms of tardive dyskinesia (72,10146,13307). Clinical research in adult and pediatric patients who are taking antipsychotic drugs shows that taking a drink containing BCAAs 222 mg/kg three times daily for 3 weeks reduces tardive dyskinesia movements by 30% to 60% when compared with placebo (10146,13307).

POSSIBLY INEFFECTIVE

Liver cancer. Oral BCAAs do not seem to improve outcomes or reduce the risk for recurrence in patients with liver cancer. Details: A meta-analysis of the available clinical research, as well as individual clinical studies, in patients with hepatocellular carcinoma show that consuming up to 50 grams of BCAAs twice daily for up to 4 years does not improve survival, reduce tumor recurrence, or reduce the risk of complications such as ascites following liver resection when compared with a control group receiving no intervention (37143,92646,97532,105578). However, one small clinical study suggests that BCAAs may be beneficial in patients recently diagnosed with hepatocellular carcinoma that does not require surgery. Taking two packets of a specific supplement (Aminoleban EN) daily containing a total of L-leucine 4 grams, L-isoleucine 3.8 grams, and L-valine 3.2 grams, starting two weeks before receiving transcatheter arterial chemoembolization and radiofrequency ablation and continuing for up to 5 years, reduces recurrence of liver cancer and increases event-free survival when compared with placebo (97533). However, the validity of these findings is limited by the high withdrawal rate in this study.

LIKELY INEFFECTIVE

Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Overall, oral BCAAs are not beneficial and might even lead to worsened outcomes in patients with ALS. Details: Although early studies have indicated that taking BCAAs might be beneficial in ALS, more recent studies show no benefit and a possible increased loss of pulmonary function and higher rate of mortality among patients using BCAAs (678,679,680,681,37154).

Alzheimer disease. It is unclear if dietary BCAAs prevent Alzheimer disease. Details: Observational research has found that higher blood levels of BCAAs are associated with an 11% to 13% lower risk of Alzheimer disease; however, when research was adjusted for mortality, body mass index, and concomitant cholesterol-lowering medications, the association was no longer significant (100469).
Athletic performance. Small clinical trials suggest that although oral BCAAs may not enhance athletic performance, they may modestly reduce perceived exertion and fatigue with some forms of exercise. Details: In most studies, taking BCAAs orally does not enhance athletic performance (692,1135,37080,37094,37106,37123,37141,37142,37151,92641). For instance, BCAAs do not appear to improve strength or work power or to reduce completion times for long-distance running or cycling trials (692,37106,37112,37141,37142,92641). However, most research shows that BCAAs are beneficial for reducing exercise-induced fatigue and perceived exertion after prolonged or intense exercise, exercise in the heat, or exercise following glycogen depletion (692,37112,37124,37144,92642,92644,92645,92648,97529,97530)(97535,105582). In many cases, this improvement is observed when BCAAs are taken in combination with arginine, citrulline, or green tea powder (37124,92642,92645,92648,97529,100462). However, some conflicting evidence exists (1135,37080,37094). Overall, the validity of these findings is limited because most studies differ widely in the amount and type of product consumed. For example, studied doses included BCAAs 0.17-0.3 mg/kg daily; or valine 0.5-1.7 grams, leucine 1-3.5 grams, and isoleucine 0.48-2.1 grams given before and/or after exercise (37108,37123,92642,92644,92645). Other limitations include variability in the studied endpoints and control comparisons used.
Bipolar disorder. It is unclear if oral BCAAs are beneficial in patients with bipolar disorder. Details: One small clinical study shows that consuming a tyrosine-free amino acid drink containing 60 grams of the BCAAs leucine, isoleucine, and valine in a ratio of 3:3:4, reduces acute manic symptoms within 6 hours when compared with placebo. When taken daily for 7 days, it seems to continue to improve symptoms over a 2-week period (10117).
Cachexia. Small clinical studies suggest that oral BCAAs are beneficial in patients with cachexia from various causes. Details: Preliminary clinical research in elderly malnourished patients receiving hemodialysis shows that taking a combination of BCAAs 4 grams three times daily improves appetite and caloric intake and increases plasma albumin levels and anthropometric measurements when compared with placebo (10147). Also, small clinical studies in adults with cachexia due to cancer or cirrhosis show that taking oral BCAAs 2.4 grams twice daily for 1 year or 4.8 grams 3 times daily for 1 week might be helpful when compared to baseline (71,37090). This finding is limited by the lack of a comparator group. A small clinical study in adults with congestive heart failure who have lost at least 7.5% of dry weight over the past 6 months or have a body mass index below 20 kg/m² shows that taking BCAAs 10 grams every evening at bedtime for 8 weeks improves physical and emotional quality of life scores, appetite, and fatigue when compared with placebo. Patients taking melatonin 20 mg nightly in addition to BCAA supplementation observed greater improvements in appetite and fatigue when compared with placebo (108478). However, a statistical comparison of outcomes between the groups taking BCAA alone or BCAA with melatonin was not provided.
Cancer. It is unclear if dietary BCAA consumption improves cancer-related mortality. Details: Observational research in adults has found that consuming BCAAs 19 grams or more daily as part of the diet is not associated with a reduced risk of cancer-related mortality when compared with a lower dietary BCAA intake of less than 7.8 grams daily (108467). The validity of this finding is limited due to unclear reporting; additionally, dietary intake was recorded from a single survey.
Cardiovascular disease (CVD). It is unclear if dietary BCAA consumption reduces the risk of CVD-related mortality. Details: Observational research in adults has found that CVD-related mortality is not associated with dietary BCAA intake or with individual leucine, isoleucine, or valine intake (108467). The validity of this meta-analysis is limited due to unclear reporting; additionally dietary intake was recorded from a single survey.
Chronic obstructive pulmonary disease (COPD). It is unclear if oral BCAAs can improve physical performance in adults with COPD. Details: A clinical study in adults with stable, stage 2 or 3 COPD undergoing a pulmonary rehabilitation program shows that taking a BCAA powder 4.3 grams, diluted in water and consumed once daily for 4 weeks, may improve recovery after exercise, but does not impact maximal exercise capacity, functional and muscular performance, or quality of life when compared with placebo (108464). The validity of these findings is limited due to the short duration of treatment.
Cirrhosis. Most small studies suggest that BCAAs may modestly improve certain measures in some patients with liver cirrhosis. Details: One small clinical study shows that although taking BCAAs 14.4 grams daily for 12 months does not improve survival or liver function in patients with advanced liver cirrhosis, the number of hospitalizations and prevalence of cachexia are reduced and quality of life is improved when compared with control or whey protein (37090). A clinical study in patients with sarcopenia and liver cirrhosis shows that taking BCAAs 7.2 grams for 6 months decreases bilirubin levels and improves Child-Turcotte-Pugh and model for end-stage liver disease (MELD) scores when compared with baseline (108468). Although the study enrolled a control group (whey protein), the investigators did not provide a statistical comparison of outcomes between groups. In addition, a small study in Japanese patients with cirrhosis shows that taking BCAAs 12.45 grams daily for at least 12 months improves liver function and reduces liver complications by 50% to 60% over 3-5 years when compared with control (37120). Also, taking a specific product (Livact, Samil Pharmaceutical) providing the same dose for 11-22 months improves liver function by a small to moderate amount over a 24-month period when compared with not taking BCAAs. There was also a moderate reduction in the rate of developing or worsening major complications such as ascites or hepatic encephalopathy (103351). However, some research providing BCAAs as part of a late evening snack has found no benefit. In one small study, consuming BCAAs as part of a late evening snack in an undefined dose for 3 months does not seem to improve quality of life when compared with a late evening snack without BCAAs (37101). Also, a very small clinical study in patients with abnormal glucose metabolism related to cirrhosis shows that consuming BCAAs in an undefined dose as part of a late evening snack for 1 week does not improve glycemic control when compared with baseline. Instead, glucose levels increased in some patients (103348). It is possible that the doses provided in these latter studies were lower than those used in the studies showing benefit. Additionally, these very small studies may not have been adequately powered to detect a difference between groups.
Colorectal cancer. It is unclear if dietary BCAAs are beneficial or harmful in patients with colorectal cancer. Details: An observational study in Italy has found that increased dietary intake of BCAAs is associated with a lower risk of developing sigmoid colon cancer, but not overall colorectal cancer risk, when compared with lower intake (105584). However, there's some concern that increased dietary BCAAs may have negative effects in patients who have been diagnosed with colorectal cancer. Observational research in patients living in the US has found that higher dietary intake of BCAAs is associated with a slightly higher risk of all-cause mortality when compared with lower intake (105581).
Dementia. It is unclear if dietary BCAAs help to prevent dementia. Details: Observational research has found that higher blood levels of BCAAs are associated with a 13% to 17% lower risk of dementia. The lowered risk was maintained when research was adjusted for mortality, body mass index, and concomitant cholesterol-lowering medications (100469).
Diabetes. It is unclear if dietary BCAAs reduce the risk for developing diabetes. Details: Some population research in Japanese females has found a decreased risk of diabetes associated with higher intake of BCAAs (97543). However, other observational research in people from the US has found that increased dietary intake of BCAAs is associated with an increased risk of diabetes (97536). Reasons for the conflicting finding are not entirely clear. Some evidence suggests that the dietary pattern of BCAA intake, rather than the total intake, may influence the risk of diabetes. Also, there is some speculation that differences in gut microbiota may attribute to the observed differences in diabetes risk associated with BCAA intake (100465). Prospective clinical research is needed to determine whether this association is causal or correlative.
Exercise-induced muscle damage. Small studies suggest that BCAAs might reduce some, but not all, markers of muscle damage caused by exercise. Details: A meta-analysis of small clinical studies shows that supplementation with BCAAs reduces creatine kinase (CK) levels 24 hours post-exercise, but not 48 hours post-exercise. Additionally, this analysis shows that lactate dehydrogenase (LDH) levels are not affected by BCAA supplementation (97534). The validity of this analysis was limited because baseline dietary protein consumption was not taken into consideration as a potential confounder. A separate meta-analysis of clinical research in trained male athletes performing various resistance exercises shows that taking BCAAs 0.2-1.76 grams/kg for 1-28 days improves CK levels immediately following exercise, and at 24 and 48 hours post-exercise, but does not reduce LDH levels at any timepoint, when compared with placebo or control (108469). Most doses of BCAAs studied consisted of a 2:1:1 ratio of leucine, isoleucine, and valine, respectively. The validity of these findings is limited due to the short duration of treatment and various doses studied. Small individual clinical trials show that taking BCAAs does not affect urinary myoglobin after a marathon nor plasma myoglobin or CK levels after isotonic muscular exercise (37123,92641,100471). The benefits of BCAAs might depend on baseline protein consumption. A small clinical study in resistance trained males shows that adding BCAAs 0.22 grams/kg (MusclePharm BCAA) daily for 8 days to a high daily protein consumption of 1.2 grams/kg does not attenuate muscle damage or improve muscle recovery when compared with placebo (100471). Conversely, a meta-analysis of clinical research in adults completing various exercises shows that taking BCAAs consisting of any combination of valine, leucine, and isoleucine ratios modestly reduces CK, LDH, and myoglobin 24 and 48 hours post-exercise, but does not improve muscle recovery or muscle force after exercise, when compared with placebo (108471). The validity of these findings is limited due to unclear reporting.
Exercise-induced muscle soreness. Limited evidence suggests that oral BCAAs may modestly attenuate exercise-induced muscle soreness. Details: One meta-analysis shows that taking BCAAs does not reduce delayed-onset muscle soreness after exercise when assessed at the individual time points of 24, 48, or 72 hours (97534). However, when results of all time points are pooled together in two separate meta-analyses, supplementation modestly reduces soreness after exercise (97534,103353). Most, but not all, individual trials also show that taking BCAAs in various doses, such as 0.087 grams/kg or 5-10 grams before and/or after exercise, modestly reduces muscle soreness after exercise (37108,37123,37124,92648,97530,97535,100467,100471,103346,108471). The validity of these individual trials is limited by their small sample sizes, variable dosing regimens, and enrolled populations, which were mainly limited to young untrained adult males (97534,103353). A separate meta-analysis of clinical research in trained male athletes performing various resistance exercises shows that taking BCAAs 0.2-1.76 grams/kg for 1-28 days may improve muscle soreness during the first 24 hours after exercise, but not at 24 or 48 hours post-exercise, when compared with placebo or control (108469). The validity of these findings is limited due to the short duration of treatment and various doses studied. Also, it is not clear whether taking BCAAs before or after a workout may be more beneficial. Some research found a nonsignificant trend toward reduced muscle soreness when consuming a specific product (Aminofeel, Seikatsu Bunkasya Co. Ltd.) containing BCAAs 3.2 grams three times daily starting 3 days before working out and continuing 3 days after, when compared to control (100467). More research is needed to determine the best dosing regimen and which populations, if any, may benefit.
Heart failure. It is unclear if oral BCAAs are beneficial in patients with heart failure. Details: A small clinical study in patients with heart failure and hypoalbuminemia shows that taking a specific packet of BCAA granules (LIVACT, Ajinomoto Co) containing L-valine 1144 mg, L-leucine 1904 mg, and L-isoleucine 952 mg, three times daily for at least 7 days and stopping after discharge from the hospital, does not affect serum albumin or cardiothoracic ratio (CTR) when compared with placebo (100470). It is possible that this study was underpowered to detect differences between groups. Another small clinical study in adults with chronic heart failure participating in a cardiac rehabilitation program shows that taking a specific oral supplement (Meiji Mei Balance Rehasupport Mini; Meiji Group) containing BCAAs 2.5 grams and various vitamins, minerals, and whey protein, twice daily for 12 weeks increases fat mass, but has no effect on peak oxygen uptake, 6-minute walking distance, or strength parameters, when compared with no supplementation (108470). It is unclear if these effects are due to BCAAs, the other ingredients, or the combination.
Hepatitis. It is unclear if oral BCAAs are beneficial in patients with hepatitis. Details: Preliminary clinical research in patients with alcoholic hepatitis shows that taking BCAAs 20 grams daily orally or enterally for 3 weeks or until discharge, in combination with a controlled diet, does not reduce the risk of mortality when compared with conventional protein or a controlled diet alone (37133).
Inflammatory myopathies. It is unclear if oral BCAAs are beneficial in patients with polymyositis and dermatomyositis. Details: A small clinical study in adults with suspected or confirmed polymyositis or dermatomyositis who are receiving standard corticosteroid therapy shows that a BCAA-specific product containing L-isoleucine 952 mg, L-leucine 1904 mg, and L-valine 1144 mg for 12-28 weeks, taken as two packages three times daily for a total daily dose of 24 grams, does not improve manual muscle test scores or clinical response at 12 and 28 weeks when compared with placebo (108477).
Obesity. It is unclear of oral BCAAs can reduce the likelihood of developing obesity or improve weight loss in adults with overweight or obesity. Details: Some observational research has found that higher dietary intake of BCAAs is associated with lower odds of obesity when compared with a lower intake (100466). Conversely, a large observational study in adults in Iran, including those who are overweight or obese, has found that the highest dietary intake of BCAAs is associated with a 24% higher likelihood of general obesity in males, but not in females, when compared with the lowest dietary BCAA intake (108465). This study did not report ranges for highest and lowest BCAA intake, limiting the validity of this study. BCAAs have also been evaluated in adults with overweight or obesity. A small clinical study in obese females that underwent a 4-week calorie-restricted diet shows that taking 6 caplets daily containing a total of L-leucine 3 grams, L-isoleucine 1.5 grams, and L-valine 1.5 grams in addition to vitamin B6 40 mg daily for 4 weeks does not further reduce weight, but may slightly preserve lean body mass, when compared with placebo (100464). Another small clinical study in overweight and obese adults shows that taking BCAAs 0.1 gram/kg daily in addition to starting a low-calorie diet for 16 weeks does not improve weight loss, but may preserve lean muscle mass, when compared with taking placebo while following the low-calorie diet (105583).
Overall mortality. It is unclear if dietary BCAA consumption reduces the risk of all-cause mortality. Details: Observational research in adults has found that total BCAA intake, as well as isoleucine intake, is associated with a reduced risk of all-cause mortality, particularly in those with higher serum triglyceride concentrations (108467). However, this association was not present for leucine or valine intake. The validity of this meta-analysis is limited due to unclear reporting; additionally dietary intake was recorded from a single survey.
Pancreatic cancer. The association between dietary BCAA intake and pancreatic cancer risk is unclear. Details: Observational research in adults in Italy has found that consuming BCAAs as part of the diet in quantities greater than 18 grams daily is associated with a 2-fold increased risk of pancreatic cancer when compared with less than 12 grams daily. This relationship was stronger in younger males, those with higher body mass indexes, and in those who smoke or have high alcohol intake (108476). Dietary information was recorded from a single, weekly consumption questionnaire.
Phenylketonuria (PKU). It is unclear if oral BCAAs are beneficial in patients with PKU. Details: A small clinical trial in adolescents and young adults with PKU shows that taking BCAAs, consisting of valine 150 mg/kg, isoleucine 150 mg/kg, and leucine 200 mg/kg, with meals and at bedtime for up to 6 months seems to improve attention and processing when compared with a control group (37127).
Physical performance. It is unclear if oral BCAAs are beneficial for improving physical function and muscle strength in older adults. Details: In malnourished elderly individuals, preliminary clinical research shows that taking a supplement providing BCAAs 5000 mg daily, in addition to other amino acids, vitamin B6, and vitamin B1 (Aminotrofic) for 2 months, does not improve muscle mass, muscle strength, or physical function to a greater extent than dietary advice intended to maximize nutritional intake from food and drink (103349). Similarly, a clinical study in middle aged and elderly adults shows that a specific product (Sarcojoint; Orient Euro Pharma, Inc) containing leucine 1 gram, arginine, vitamin D3, glucosamine, chondroitin, and calcium, taken twice daily in addition to regular resistance exercise for 12 weeks, does not improve muscle strength, muscle mass, or physical performance when compared with taking an unspecified vitamin B supplement twice daily with regular exercise (108472). Conversely, one small clinical study in older adults who have had a hip replacement shows that taking BCAAs 1.2 grams and lysine 1.8 grams (Amino-aile, Ajinomoto Co., Inc.) daily for one month after undergoing exercise therapy sessions modestly increases the strength of both legs and arms when compared with taking starch. However, there was no effect on hip abductor strength of the operated leg or on grip strength or measures of independence (103347).
Postoperative infection. There is limited evidence on the intravenous and oral use of BCAAs for reducing infection after oncologic surgery. Details: A meta-analysis of 6 small heterogeneous clinical trials in patients after oncologic surgery, mostly for liver cancer, suggests that receiving oral or intravenous BCAAs reduces the risk of postoperative infection by 38% when compared with control (105577).
Postoperative recovery. There is limited evidence on the intravenous and oral use of BCAAs for improving postoperative recovery after oncologic surgery. Details: A meta-analysis of small heterogeneous clinical trials in patients after oncologic surgery, mostly for liver cancer, suggests that receiving oral or intravenous BCAAs reduces hospital stay by about 2 days, but does not reduce mortality or post-operative complications, when compared with control (105577).
Psychological well-being. It is unclear if oral BCAAs are beneficial for psychological well-being. Details: A cross-sectional observational study has found that higher dietary consumption of BCAAs is associated with a lower risk of anxiety and depression when compared with lower consumption (105579).
Sarcopenia. It is unclear if oral BCAAs are beneficial in patients with primary sarcopenia or in those with sarcopenia related to liver cirrhosis. Details: A small clinical study in postmenopausal adults at risk for sarcopenia shows that consuming BCAAs 9 grams daily for 8 weeks in addition to resistance training increases strength and muscle mass when compared with baseline, but is no different than resistance training plus a placebo (105576). Another small clinical study in adults 65 years or older with sarcopenia shows that taking a supplement containing BCAAs 2500 mg, vitamin D 500 IU, protein, and other vitamins daily for 8 weeks in addition to resistance training does not improve physical function when compared with resistance training alone. The supplement did seem to slightly improve handgrip strength and body mass when compared with no supplementation (100468). However, overall the study was inadequately powered to detect smaller effects on physical function and muscle mass. There is also interest in using BCCAs in patients with sarcopenia and liver cirrhosis. A clinical study in this population shows that taking BCAAs 7.2 grams (containing 1.2 grams of L-leucine, 600 mg of L-isoleucine, and 600 mg of L-valine) daily for 6 months improves handgrip strength, gait speed, and muscle mass when compared with baseline (108468). Although the study enrolled a control group (whey protein), the investigators did not provide a statistical comparison of outcomes between groups. A separate meta-analysis of low-quality clinical research in this population shows that taking BCAAs has no effect on handgrip strength when compared with no supplementation (108473). Although other outcomes were evaluated, results are inconclusive due to the limited number of studies available for each outcome.
Spinocerebellar ataxia (SCA). It is unclear if oral BCAAs are beneficial in patients with SCA. Details: Although there is some preliminary clinical evidence that oral BCAAs might have a beneficial effect on symptoms of SCA (73), a small clinical crossover study shows that taking a particular BCAA compound (Livact) 4.5-18 grams daily for 4 weeks does not improve ataxia in patients with SCA when compared with placebo (37088).
Stroke. It is unclear if oral BCAAs are beneficial in patients recovering from stroke. Details:A small nonblinded, clinical study in elderly patients with subacute stroke and sarcopenia currently undergoing intensive inpatient rehabilitation therapy shows that administering a specific product (Seniup; Enterogenomics Co) containing BCAAs 6 grams, given twice daily orally or by feeding tube for 1 month, modestly improves skeletal muscle index, dysphagia, gait, balance, and handgrip strength, and may attenuate muscle loss in affected upper and lower extremities, when compared with rehabilitation alone (108474). The validity of these findings is limited by the short duration of treatment. Other research has compared BCAA dosing regimens. A small study in stroke patients taking part in exercise sessions shows that taking BCAAs 3.5 grams (Hepas, Clinico Co. Ltd) daily for 2 months with breakfast is more effective for improving leg strength and balance than when taken post-exercise in the mid-afternoon. However, there were no differences in most measures of strength or in skeletal muscle mass (103352). More evidence is needed to rate BCAAs for these uses.

Atopic dermatitis (eczema). Topical coconut oil has been evaluated for the management of atopic dermatitis in children, with promising results. Details: One clinical trial in children with atopic dermatitis shows that topical application of virgin coconut oil 5 mL twice daily for 8 weeks results in moderate or excellent improvements in almost two-fold more patients and reduces symptom severity about 30% when compared with mineral oil (90614).
Prematurity. Topical coconut oil may reduce the risk for hypothermia and apnea and improve body weight, length, and skin integrity in premature infants. Details: A large clinical study in premature infants shows that applying coconut oil 5 mL topically four times daily for 28 days reduces the incidence of hypothermia and apnea by 67% and 76%, respectively, when compared with body massage without oil. There were also improvements in the level of vitamin D3 and the overall neurodevelopmental score over 12 months (101873). Clinical studies in premature infants also show that oil massage using coconut oil reduces weight loss in the first few days after birth and improves weight gain and length when compared with mineral oil or no application (17937,90616,101873). Preterm infants are at increased risk for infection due to the inadequate protective barrier provided by immature skin. Clinical studies in preterm or very preterm infants show that topical application of virgin coconut oil 2-4 times daily for 21-28 days as part of routine neonatal care helps maintain skin integrity, but does not reduce the risk for infections such as sepsis, when compared with routine neonatal care alone (96204,101873). Another clinical study in preterm infants shows that topical application of coconut oil 5 mL/kg twice daily for 28 days reduces the incidence of hospital-acquired infections from 21% to 7% when compared with control, but does not reduce overall mortality (90616).

Alzheimer disease. Although there has been interest in using oral coconut oil for Alzheimer disease, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
Athletic performance. It is unclear if oral coconut oil is beneficial for improving athletic performance. Details: A small clinical trial in recreational runners shows that taking virgin coconut oil (Copra Alimentos, Maceio) 15 grams, with or without caffeine 6 mL/kg, 60 minutes prior to a 1600 meter running trial does not improve running performance or ratings of exertion when compared with a warm water control (101874).
Breast cancer. It is unclear if oral coconut oil is beneficial in patients with breast cancer. Details: A small clinical study in patients with invasive or advanced breast cancer shows that taking virgin coconut oil 10 mL twice daily starting one week after chemotherapy from the third to the sixth cycle improves quality of life based on some but not all measurement scales when compared with control (90615).
Coronary heart disease (CHD). Small clinical studies suggest that oral coconut oil does not alter the risk of CHD or prevent cardiovascular events in patients with CHD. Details: One small observational study in India has found that coconut or coconut oil consumption is not associated with a decreased or increased risk of myocardial infarction or angina (14407). A small clinical trial in patients with CHD from India shows that cooking with coconut oil does not alter cardiovascular outcomes or risk factors at 6 months, 1 year, or 2 years when compared with cooking with sunflower oil (96205).
Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral coconut oil for COVID-19, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
Crohn disease. Although there has been interest in using oral coconut oil for Crohn disease, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
Dental plaque. Small clinical studies suggest that pulling coconut oil through the teeth may modestly reduce dental plaque. Details: A small clinical study shows that pulling coconut oil 10 mL through the teeth for 15-20 minutes twice daily for 4 days is as effective as using a mouth rinse containing chlorhexidine gluconate-0.2% as 10 mL twice daily for 30 seconds in the prevention of plaque regrowth in posterior, but not anterior, surfaces of the teeth (101878). Another small clinical study in patients with plaque-induced gingivitis shows that pulling coconut oil 10 mL through the teeth for 5-10 minutes nightly for 30 days improves plaque scores when compared with standard dental hygiene with no mouth rinse (106491).
Diabetes. It is unclear if oral coconut oil is beneficial for diabetes. Details: A meta-analysis of clinical trials shows that a single intake of coconut oil as part of a meal modestly increases postprandial glucose levels and decreases insulin levels. However, long-term intake of coconut oil increases insulin resistance, with no effect on fasting blood glucose or insulin levels. Only two studies in these analyses included patients with diabetes (107667). Therefore, the effect of coconut oil in patients with diabetes is unclear.
Diarrhea. It is unclear if oral coconut oil is beneficial for improving diarrhea in children. Details: One small clinical study in children with mild-to-moderate dehydration due to diarrhea shows that eating a diet consisting of coconut oil, chicken, and plantain reduces the duration of diarrhea by 20 hours when compared with a cow's milk diet (19269). However, another small clinical trial in children with acute gastroenteritis shows that total duration of diarrhea is no different in children given a milk-free formula containing coconut oil when compared with children given cow's milk formula (19270).
Dry mouth. It is unclear if topical coconut oil is beneficial for improving dry mouth in patients receiving radiation therapy. Details: One small clinical study in patients with dry mouth caused by radiation therapy shows that coating the mouth with coconut oil prior to meals and at bedtime for 2 weeks does not improve dry mouth-related quality of life scores when compared to baseline (106490).
Dry skin. It is unclear if topical coconut oil is beneficial for improving dry skin. Details: A small clinical study in patients with mild-to-moderate dry skin shows that applying coconut oil topically twice daily improves skin moisture and skin lipid levels when compared to baseline. Coconut oil seems to be comparable to mineral oil as a skin moisturizer (17936). Also, preliminary clinical research in individuals who apply alcohol-based sanitizers to the hands six times daily shows that applying 6-8 drops (0.1 mL/cm²) of virgin coconut oil to the hands before bed for 15 days modestly increases perceived moisture content, but not perceived appearance or sensation, when compared with not using coconut oil (107668).
Fetal and premature infant mortality. It is unclear if topical coconut oil is beneficial for reducing mortality in premature infants. Details: One clinical study in preterm infants shows that topical application of coconut oil 5 mL/kg twice daily for 28 days reduces the incidence of hospital-acquired infections from 21% to 7% when compared with control, but does not reduce overall mortality (90616).
Gingivitis. It is unclear if pulling coconut oil through the teeth is beneficial in patients with gingivitis. Details: A small clinical study in patients with plaque-induced gingivitis shows that pulling coconut oil 10 mL through the teeth for 5-10 minutes nightly for 30 days improves gingival bleeding scores when compared with standard dental hygiene without a mouth rinse (106491). Another small clinical study in volunteers with gingival inflammation shows that pulling extra virgin coconut oil, 5 mL, through the teeth for 8 minutes daily for 28 days does not change plaque microbial counts when compared with baseline or with palm oil pulling (110010).
HIV/AIDS. Although there has been interest in using oral coconut oil for HIV/AIDS, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
Hypertension. It is unclear if oral coconut oil is beneficial in patients with hypertension. Details: One small clinical study in patients with hypertension shows that taking extra virgin coconut oil 3 mL with breakfast, 4 mL with lunch, and 3 mL with dinner daily for 30 days does not reduce blood pressure when compared with placebo (106493).
Irritable bowel syndrome (IBS). Although there has been interest in using oral coconut oil for IBS, there is insufficient reliable information about the clinical effects of coconut oil for this purpose.
Lice. Topical coconut oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in children with head lice shows that application of a topical spray containing coconut oil, anise oil, and ylang ylang oil (Chick-Chack) once every 5 days for three treatments eradicates lice in around 92% of infected children, a rate comparable to children treated with a spray containing permethrin, malathion, piperonyl butoxide, and isododecane (13483). It is unclear if these findings are due to coconut oil, other ingredients, or the combination.
Low birth weight. It is unclear if oral coconut oil is beneficial for improving growth in infants with very low birth weight. Details: One small, open-label clinical trial in very low birth weight infants shows that giving coconut oil 1 mL four times daily in expressed breast milk until 40 weeks corrected age does not increase growth when compared with breast milk alone. The addition of coconut oil also has no effect on head circumference, length, weight, or body fat improvements (101875).
Metabolic syndrome. It is unclear if oral coconut oil is beneficial in patients with metabolic syndrome. Details: One small clinical trial in patients with metabolic syndrome shows that using 30 mL of virgin coconut oil in place of other cooking oils daily for 4 weeks reduces levels of triglycerides, very low-density lipoprotein (VLDL) cholesterol, and fasting plasma glucose and increases high-density lipoprotein (HDL) cholesterol levels when compared with a usual diet. However, levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were increased with coconut oil use. Coconut oil did not alter blood pressure or waist circumference (106494).
Multiple sclerosis (MS). Oral coconut oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with MS shows that taking coconut oil 60 mL in combination with epigallocatechin gallate (EGCG) 800 mg daily for 4 months improves functional capacity, increases muscle mass, and reduces symptoms of anxiety and depression by a small amount when compared to baseline (101876,106492). It is unclear if these findings are due to coconut oil, EGCG, or the combination. Additionally, the validity of these findings is limited by the lack of a comparator group.
Nipple fissures. It is unclear if topical coconut oil is beneficial for nipple fissures in breastfeeding mothers. Details: Preliminary clinical research in breastfeeding primiparous mothers with nipple fissures shows that applying 0.5 mL of virgin coconut oil to the fissures after breastfeeding three times daily for 14 days improves scores on Storr's fissure scale and on a visual analog pain scale, when compared with applying 3 to 4 drops of breastmilk to the nipples after every breastfeeding session (110407).
Nocturnal enuresis. It is unclear if topical coconut oil is beneficial in children with primary nocturnal enuresis. Details: Preliminary clinical research in children aged 6 to 14 years with primary nocturnal enuresis shows that applying coconut oil, 6 drops to the suprapubic, sacral, and flank areas nightly for 4 weeks reduces the mean frequency of urination at 4 weeks and 8 weeks of follow-up, when compared with baseline. Complete resolution occurred in 24 patients receiving coconut oil, and 17 receiving the paraffin oil control. There was no improvement in 5 on coconut oil, and 14 on paraffin oil (110405). However, the validity of these findings is unclear since blinding was compromised by the different oil odors.
Obesity. Although some clinical studies suggest that oral coconut oil may modestly reduce body weight or body mass index (BMI), most research is mixed. Details: A meta-analysis of clinical research shows that taking coconut oil in the diet or as a supplement daily decreases body weight, BMI, and fat mass percent by 0.75 kg, 0.28 kg/m², and 0.35%, respectively, when compared to other oils and fats, usually polyunsaturated oils. However, there was no effect on waist circumference or total fat mass, and significant changes did not occur in more than half of the individual studies (107665). These individual studies were generally small, of low to moderate quality, and utilized a wide range of dosing regimens. Doses of coconut oil used in the individual studies ranged from 7-93 mL or 14% to 15% of daily energy intake and included extra-virgin, virgin, bleached and deodorized, hydrogenated, and ordinary sources. Study durations ranged from 4 weeks to 2 years (17938,17942,99102,107665). Virgin coconut oil is associated with reduced hunger and desire to eat in normal weight subjects, but not in obese subjects, when compared with extra virgin olive oil. It is also associated with reduced energy intake at the next meal when compared with olive oil in obese subjects, but not in normal weight subjects (110406).
Psoriasis. It is unclear if topical coconut oil is beneficial in patients with psoriasis. Details: One small clinical study in patients with psoriasis shows that applying coconut oil to the skin before treatment with ultraviolet B (UVB) or psoralen and ultraviolet A (PUVA) phototherapy does not seem to improve the clearance of psoriasis (12356). More evidence is needed to rate coconut oil for these uses.

CONJUGATED LINOLEIC ACID (CLA) (Conjugated Linoleic Acid)

Hypertension. Oral CLA seems to modestly reduce blood pressure when used along with ramipril. However, oral CLA alone does not seem to reduce blood pressure. Details: A meta-analysis of small clinical trials shows that taking CLA in doses of 1 gram to 10.8 grams daily does not lower systolic or diastolic blood pressure when compared with placebo or a control diet (111053). However, this analysis is limited by the heterogeneous populations in the individual studies. Only one study was specifically conducted in individuals with hypertension (45569). This small clinical trial in individuals with stage one uncontrolled hypertension shows that taking CLA 4.5 grams daily along with ramipril 37.5 mg daily for 8 weeks modestly reduces systolic and diastolic blood pressure when compared with ramipril alone (45569).
Obesity. In adults and children, oral CLA seems to decrease fat mass by a small amount, including abdominal fat mass. However, it is unclear if oral CLA is beneficial for weight loss, body mass index (BMI) reduction, or improvement of metabolic measures. Details: Taking CLA 3-6.8 grams daily seems to decrease body fat mass, increase lean body mass, and reduce waist and hip circumference in some patients (2819,3153,4947,13137,45295,45303,45685,45799,97003,105809). A meta-analysis of clinical research in adults with overweight or obesity also undergoing an exercise program shows a small effect on body fat reduction, but not body weight or plasma lipids (111056). Most research suggests that doses greater than 3.4 grams daily do not seem to offer any additional benefit when compared with lower doses (2819,2821,3153,4947,10410,11327,13137,45295,45799). Also, supplementing milk with CLA 3 grams daily seems to reduce total fat mass in individuals with overweight when compared with placebo (45331). CLA also seems to reduce hunger and improve satiety and feelings of fullness, but this appetite suppression does not necessarily result in a lower energy intake or improved body weight maintenance (11327). In children with overweight aged 6-10 years, taking CLA 3 grams daily for approximately 7 months seems to reduce body fat, abdominal fat, and peripheral fat percentages when compared with placebo (45713). There is inconsistent evidence regarding the effects of CLA on body weight and BMI, with most research suggesting that CLA does not reduce total body weight or BMI (2819,2821,3153,10410,13137,45007,45679,45790,97003,97006). Also, taking CLA in combination with omega-3 fatty acids or chromium picolinate does not seem to improve BMI and body weight in individuals with overweight or obesity (42627,45431). Although one meta-analysis of clinical research shows that taking CLA 2.4-6 grams daily for 6-12 months increases weight loss by 0.7 kg and fat loss by 1.3 kg when compared with placebo, this effect is small and may not be clinically significant (91585). Also, taking CLA 3.4 grams daily for 1 year does not seem to prevent weight or body fat regain in individuals with overweight who previously lost some of their initial body weight (45083,45221). However, one study shows that taking CLA 8 grams daily for 16 weeks seems to reduce BMI in obese, postmenopausal adults with type 2 diabetes (45614). Some studies have evaluated the consumption of CLA-enriched fatty foods. In males with overweight, consuming butter enriched with CLA does not seem to have beneficial metabolic effects (45192). Also, in individuals with overweight or obesity, consuming a goat cheese naturally enriched in CLA and omega-3 fatty acids for 12 weeks does not seem to improve BMI, fat mass, or weight, or most metabolic measures, including fasting glucose, blood pressure, or inflammatory factors, when compared to a control goat cheese. However, there was an increase in total cholesterol, possibly related to an increase in high-density lipoprotein (HDL) cholesterol, and reduced levels of C-reactive protein (CRP) (105808). There is evidence that the isolated trans-10,cis-12 isomer of CLA can increase hyperproinsulinemia and insulin resistance in patients with abdominal obesity (2821,13026,13137). Hyperproinsulinemia is an independent risk factor for type 2 diabetes and cardiovascular disease. Therefore, CLA might not be a good choice for obese patients. However, most commercial CLA products contain a mixture of CLA isomers. It is not known if these mixed CLA isomer products carry this risk. One meta-analysis of clinical research shows that insulin resistance is modestly reduced when a CLA supplement is taken by adults undergoing an exercise program when compared with exercise alone (111056).

POSSIBLY INEFFECTIVE

Common cold. Oral CLA does not seem to be beneficial for common cold prevention or treatment. Details: Some clinical research shows that taking CLA 2 grams daily does not reduce the risk of developing a cold or reduce cough or sore throat severity in individuals with a common cold when compared with placebo (45577).
Diabetes. Oral CLA does not seem to be beneficial for diabetes. Details: Some clinical research shows that taking CLA 6.4 grams daily for 16 weeks does not improve fasting glucose, postprandial glucose, or insulin in individuals with type 2 diabetes when compared with safflower oil (45614,45835).
Hyperlipidemia. Oral CLA does not seem to be beneficial for hyperlipidemia. Details: A meta-analysis and individual clinical trials show that taking CLA as supplements or fortified foods does not improve levels of cholesterol or triglycerides (45790,97006,111054). One meta-analysis of small clinical trials in heterogenous populations shows that taking CLA does not improve levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides, and modestly DECREASES levels of high-density lipoprotein (HDL) cholesterol, when compared with taking placebo or a control diet (111054). CLA has generally been taken in doses of 1.4 to 6.8 grams daily for up to 24 weeks (45790,97006,111054). However, research in patients with hyperlipidemia is limited. Most studies have included general populations of healthy adults, patient with type 2 diabetes, or populations with obesity.

Allergic rhinitis (hay fever). It is unclear if oral CLA is beneficial for reducing symptoms of allergic rhinitis. Details: Clinical research shows that taking CLA 2 grams daily for 12 weeks improves overall well-being in patients with birch pollen allergy when compared with placebo, but does not improve eye or total allergy symptoms (45395).
Asthma. It is unclear if oral CLA is beneficial for reducing symptoms of asthma. Details: A small clinical trial in patients with mild asthma shows that taking CLA 4.5 grams daily for 12 weeks improves airway hypersensitivity and tolerance to strenuous exercise when compared with placebo, but without significantly reducing the need to use rescue bronchodilators or improving lung capacity (45787). In addition, a small clinical trial in children 6-18 years of age with allergic asthma shows that taking CLA 3 grams daily for 12 weeks does not reduce the use of emergency bronchodilators or improve peak expiratory flow, forced expiratory volume (FEV1), or vital lung capacity when compared with placebo (97005).
Atherosclerosis. Although there is interest in using oral CLA for preventing atherosclerosis, there is insufficient reliable information about the clinical effects of CLA for this purpose.
Athletic performance. It is unclear if oral CLA is beneficial for improving athletic performance. Details: Some preliminary clinical research in student athletes shows that taking CLA powder (CLAce Powder, The Nisshin OilliO Group, Ltd.) 900 mg daily for 14 days increases time to exhaustion during exercise by an average of 179 seconds, but does not reduce rate of perceived exertion, when compared with placebo (97002). Other small clinical trials show that taking a specific product containing CLA oil (Clarinol A-80, Stepan Specialty Products, LLC) 5.63 grams daily for 6 weeks in combination with aerobic training does not improve muscle endurance, muscle power, peak oxygen uptake, or cardiorespiratory fatigue threshold when compared with placebo in untrained to moderately trained males (91587,91588).
Breast cancer. It is unclear if dietary CLA is beneficial for preventing breast cancer. Details: Some observational research has found that a higher intake of CLA in foods, particularly cheese, is linked with a lower risk of developing breast cancer in postmenopausal individuals (5058). However, other population research has found that intake of CLA is not associated with a reduced risk of breast cancer (45609). Furthermore, some epidemiological evidence has found that CLA intake might be weakly associated with an increased risk of breast cancer (45048).
Cognitive function. It is unclear if oral CLA is beneficial for improving cognitive function in older adults. Details: Preliminary clinical research in older adults shows that taking CLA 1.75 grams twice daily for 6 weeks may modestly improve verbal learning and recall in males, but not females, when compared with placebo (97008).
Colorectal cancer. It is unclear if dietary CLA is beneficial for preventing colorectal cancer. Details: Epidemiological research has found that high dietary intake of CLA might reduce the risk of colorectal cancer in females by up to 39% (13775). It is not known if taking CLA supplements is associated with a reduced risk of colorectal cancer.
Metabolic syndrome. It is unclear if oral CLA is beneficial for metabolic syndrome. Details: Evidence from a small clinical trial shows that taking CLA 3 grams daily orally for 90 days, along with a hypocaloric diet, decreases body fat mass by approximately 3% when compared to baseline in females with metabolic syndrome. However, this reduction does not appear to be significant when compared with placebo treatment, and CLA does not lower blood lipid levels or blood pressure (91586).
Muscle strength. It is unclear if oral CLA is beneficial for increasing muscle strength. Details: Some preliminary clinical research shows that adding CLA 6 grams to supplementation with creatine 9 grams and whey protein 36 grams daily for 12 weeks modestly enhances strength improvement and lean tissue mass when compared with placebo in adults participating in strength training (45596). However, other clinical research shows that taking CLA 5 grams daily for 7 weeks does not improve most measures of strength in adults participating in resistance training when compared with placebo, although bench press strength was modestly improved in males, and lean tissue mass and fat mass were also improved (45222). Other clinical research shows that taking CLA 6 grams daily for 4 weeks does not improve body composition or strength in resistance-trained athletes (45041). The reasons for these discrepancies are unclear, but may be related to the duration of treatment.
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral CLA is beneficial for NAFLD. Details: Preliminary clinical research shows that taking CLA (Nutrifit, Nutricentury) 1 gram three times daily in conjunction with a weight loss diet for 8 weeks reduces fat mass, low-density lipoprotein (LDL) cholesterol levels, and alanine aminotransferase (ALT) levels and increases muscle mass when compared with a weight loss diet alone in obese adults with NAFLD. CLA was also associated with a reduction in glycated hemoglobin, but with no corresponding reduction in fasting plasma glucose (97004).
Physical performance. It is unclear if oral CLA is beneficial for improving physical performance in older adults. Details: Preliminary clinical research in adults 65-85 years of age shows that taking CLA 1.75 grams twice daily for 6 weeks does not improve handgrip strength or hand discomfort when compared with placebo (97008).
Rheumatoid arthritis (RA). It is unclear if oral CLA is beneficial for RA. Details: Preliminary clinical research shows that taking CLA 2.5 grams daily with or without vitamin E 400 mg daily for 12 weeks reduces pain and morning stiffness and reduces erythrocyte sedimentation rate in patients with RA when compared to baseline (45730). The validity of these findings is limited by the lack of a comparator group. More evidence is needed to rate conjugated linoleic acid for these uses.

Hypercholesterolemia. Several small studies suggest that oral safflower oil, as a substitute for coconut oil, butter, or other animal fats in the diet, may reduce total and low-density lipoprotein (LDL) cholesterol levels in patients with or without hypercholesterolemia. Details: Three small clinical studies in patients with or without hypercholesterolemia show that substituting coconut oil, butter, or other animal fats in the diet with safflower oil (36% of total daily calories) for 4-6 weeks can lower levels of total and LDL cholesterol, but has no beneficial effects on high-density lipoprotein (HDL) cholesterol or triglycerides (25391,25393,72310).

Coronary heart disease (CHD). Safflower oil, which is high in oleic acid, may be beneficial for reducing the risk of CHD when used to replace other dietary oils. Details: Some safflower oil products contain high quantities of oleic acid. In 2018, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that consuming 1.5 tablespoons daily of oils containing at least 70% oleic acid may reduce the risk of CHD. In order to obtain any benefit, this oil must be used to replace fats and oils higher in saturated fat. However, the FDA has determined that this statement is based on supporting, rather than conclusive, evidence (98563).
Cystic fibrosis. It is unclear if oral safflower oil is beneficial in children with cystic fibrosis. Details: A very small clinical study in children with cystic fibrosis shows that taking safflower oil 1 gram/kg daily for one year does not affect sweat chloride concentrations or disease severity when compared with age-matched controls (72281).
Diabetes. Small clinical studies of oral safflower oil for improving glycemic control in patients with diabetes have yielded mixed results. Details: One very small clinical trial in patients with type 2 diabetes shows that taking safflower oil 10 grams daily for 3 weeks increases fasting blood glucose by 11% when compared to baseline. Insulin levels, insulin sensitivity, and lipid levels were not affected (13146). However, another small clinical study in obese, postmenopausal patients with type 2 diabetes shows that taking safflower oil 2 grams four times daily for 16 weeks decreases HbA1c by 0.64% and increases high-density lipoprotein (HDL) cholesterol by about 5 mg/dL when compared with conjugated linoleic acid (CLA) 2 grams four times daily. Insulin sensitivity and fasting blood glucose levels do not appear to be affected (94039). These differing outcomes may be due to the small study sizes and varied patient populations.
Diabetic nephropathy. Small clinical studies suggest that intravenous safflower yellow, a component of safflower flower, might improve symptoms and markers of diabetic nephropathy. Details: A meta-analysis of 14 small and low-quality clinical studies in adults with diabetic nephropathy shows that intravenous administration of safflower yellow as an adjunct to conventional treatment reduces urinary albumin excretion rate, fasting blood glucose, serum creatinine, and blood urea nitrogen when compared with conventional treatment alone. Overall, patients receiving safflower yellow were more likely to experience a clinical improvement in symptoms when compared with conventional treatment alone (102381).
Familial hypercholesterolemia. Small clinical studies suggest that substituting safflower oil in place of butter in the diet may modestly reduce cholesterol levels in patients with familial hypercholesterolemia. Details: Two very small clinical studies in patients with familial hypercholesterolemia show that substituting safflower oil in place of butter in the diet (contributing 36% of daily calories) for 3 weeks decreases total and low-density lipoprotein (LDL) cholesterol levels when compared with butter (72246,72267).
Hepatitis C. Oral safflower oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, open-label clinical study in patients with chronic hepatitis C shows that taking a specific combination product containing safflower, pumpkin seeds, plantain seeds, and Japanese honeysuckle (EH0202) 1 gram daily for 3 months modestly reduces general discomfort, abdominal bloating, nausea, and vomiting when compared to baseline. However, hepatitis C RNA and hepatitis C virus antibody levels are not affected (72238).
Hypertension. It is unclear if oral safflower oil is beneficial for reducing blood pressure; the available research is conflicting. Details: A very small clinical study in patients with hypertension shows that taking safflower oil 10 mL twice daily for 6-8 weeks reduces diastolic blood pressure when compared with placebo (72304). However, another small clinical study in patients with mild hypertension shows that taking safflower oil 30 mL daily for 6 weeks does not affect blood pressure when compared to baseline (72268).
Low birth weight. It is unclear if oral safflower oil is beneficial in infants with low birth weight. Details: A small clinical study in low birth weight infants shows that fortifying formula or breast milk with a specific safflower oil product (Safola, Marico Industries Ltd.) does not improve weight gain or skin thickness when compared with coconut oil or unfortified formula or breast milk (72229).
Metabolic syndrome. It is unclear if oral safflower oil is beneficial in patients with metabolic syndrome. Details: A small clinical study in patients with metabolic syndrome shows that taking safflower oil 2 grams four times daily for 12 weeks reduces waist circumference by 3.4 cm, systolic blood pressure by 7 mmHg, diastolic blood pressure by 3 mmHg, and fasting blood glucose by 8 mg/dL when compared with placebo. However, body weight, body mass index (BMI), and lipid levels were not affected (108889).
Obesity. Although there has been interest in using oral safflower oil for obesity, there is insufficient reliable information about the clinical effects of safflower oil for this purpose.
Myocardial infarction. Intravenous safflower yellow, a component of safflower flower, might improve outcomes when used as an adjunct to conventional therapy for the treatment of acute coronary syndrome (ACS). Details: A meta-analysis of 16 small, low-quality clinical trials in patients with ACS, including myocardial infarction and unstable angina, shows that intravenous administration of safflower yellow 20-40 mL daily for 10-15 days as an adjunct to conventional therapy improves clinical outcomes, electrocardiogram measures, and left ventricular ejection fraction when compared with placebo (108891).
Phrynoderma. It is unclear if oral safflower oil is beneficial in patients with phrynoderma. Details: A small clinical study in patients with phrynoderma shows that taking 30 mL of safflower oil containing vitamin E 116 mg and linoleic acid 68% daily for more than 8 weeks can partially improve skin dryness and roughness when compared to baseline (72269). The validity of these findings is limited by the lack of a comparator group.
Scarring. Topical safflower oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with non-hypertrophic scars and striae shows that applying an oil containing safflower oil 55.9%, olive oil 42%, grapefruit oil 2%, and tocopherol 0.1% (Kneipp Bio Skin Oil, Kneipp GmbH) to the scars and striae twice daily for 8 weeks improves scores on the Patient Scar Assessment Scale (PSAS) by 20%, compared to a 6% improvement in untreated areas (95938).
Stroke. Small clinical studies suggest that intravenous safflower yellow, a constituent of safflower flower, as an adjunct to conventional treatments, may improve neurological outcomes post-stroke. Details: A meta-analysis of seven small, low-quality clinical studies in Chinese patients with acute ischemic stroke shows that intravenous administration of safflower yellow 100-150 mg as an adjunct to conventional treatments, starting within 72 hours of stroke onset and continuing once daily for 14 days thereafter, increases the odds of neurological improvement by about 3-fold when compared with conventional treatments alone (94038).
Unstable angina. Intravenous safflower yellow, a component of safflower flower, might improve outcomes when used as an adjunct to conventional therapy for the treatment of unstable angina. Details: A meta-analysis of seven low-quality clinical studies in Chinese patients with unstable angina shows that intravenous safflower yellow 50-150 mg daily for 14-15 days in addition to conventional treatment modestly improves electrocardiogram (ECG) measures and symptoms of angina when compared with conventional treatment alone (94041). Another meta-analysis of 16 small, low-quality clinical trials in patients with acute coronary syndrome (ACS), including unstable angina and myocardial infarction, shows that intravenous administration of safflower yellow 20-40 mL daily for 10-15 days as an adjunct to conventional therapy improves clinical outcomes, ECG measures, and left ventricular ejection fraction when compared with placebo (108891). More evidence is needed to rate safflower for these uses.

Safety view details

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

AGMATINE

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Agmatine sulfate has been used with apparent safety at doses up to 2.67 grams daily for up to 2 months and 3.56 grams daily for up to 3 weeks (94736,111144).

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

LIKELY SAFE ...when the fruit is consumed in amounts commonly found in foods (668,669,670,671).

POSSIBLY SAFE ...when the oil is applied to the skin topically and appropriately, short-term. Avocado oil in combination with vitamin B12 appears to be safe when used for up to 12 weeks (14909). There is insufficient reliable information available about the safety of avocado for its other uses.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in amounts exceeding those commonly found in foods.

BRANCHED-CHAIN AMINO ACIDS (BCAA) (Glycyl-Alanyl-Lysine-L-Leucine, Glycyl-Alanyl-Lysine-L-Isoleucine, Glycyl-Alanyl-Lysine-L-Valine)

LIKELY SAFE ...when used orally and appropriately. BCAAs 12 grams daily have not been associated with significant adverse effects in studies lasting for up to 2 years (68,72,73,74,10117,10146,10147,37120,92643,97531,103351,103352). ...when used intravenously and appropriately. BCAAs are an FDA-approved injectable product (13309).

CHILDREN: LIKELY SAFE
when used orally in dietary amounts of 71-134 mg/kg daily (11120,13308).

CHILDREN: POSSIBLY SAFE
when larger, supplemental doses are used orally and appropriately for up to 6 months (13307,13308,37127).

PREGNANCY:
Insufficient reliable information available; avoid using amounts greater than those found in food. Although adverse effects have not been reported in humans, some animal research suggests that consumption of supplemental isoleucine, a BCAA, during the first half of pregnancy may have variable effects on birth weight, possibly due to abnormal placental development (103350).

LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food. Although the safety of increased BCAA consumption during lactation is unclear, some clinical research suggests that a higher concentration of isoleucine and leucine in breastmilk during the first 6 months postpartum is not associated with infant growth or body composition at 2 weeks, 2 months, or 6 months (108466).

LIKELY SAFE ...when used orally in food amounts. Coconut oil can be safely consumed as a component of the diet (12361,17935,94452,106494). However, coconut oil should not be considered a healthy alternative to other saturated fats (94453,94643). Coconut oil contains more saturated fat than animal based fats, including lard and butter (94643). Therefore, like all saturated fats, coconut oil should be used in moderation (94453,94643). ...when used topically and appropriately. Commercial products containing coconut oil in concentrations up to 100% have been used with apparent safety. However, most research has used commercial products with concentrations up to 70% (12356,17936,17941).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Taking coconut oil up to 10 mL orally two or three times daily for up to 12 weeks has been used with apparent safety in clinical research (17938,17942,90615,106493).

CHILDREN: POSSIBLY SAFE
when used topically and appropriately, short-term. Coconut oil has been used with apparent safety in children and neonates for about one month (13483,17937,90614,90616,96204,101873). There is insufficient reliable information available about the safety of coconut oil when taken orally in children.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of using coconut oil in medicinal amounts during pregnancy or lactation. Coconut oil ingestion increases the amount of lauric acid in breast milk within 10 hours. This indicates that fatty acids from coconut oil are rapidly transferred into human breast milk following oral intake (14086). The impact of this increase in lauric acid on nursing infants is not known.

CONJUGATED LINOLEIC ACID (CLA) (Conjugated Linoleic Acid)

LIKELY SAFE ...when used orally in amounts found in foods. CLA occurs naturally in milk fat, beef, and the meat of other ruminant animals (5924,5925,5932,5933).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts of up to 6. 8 grams daily, short-term (2819,2821,3153,4947,10410,11327,111056).

CHILDREN: LIKELY SAFE
when used orally in amounts found in foods. CLA occurs naturally in milk fat, beef, and the meat of other ruminant animals (5924,5925,5932,5933).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts. Some evidence suggests that CLA 3 grams daily can be taken safely for up to 7 months (45713).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods (5924,5932,5933). There is insufficient reliable information available about the safety of CLA when used in medicinal amounts during pregnancy or lactation; avoid using.

LIKELY SAFE ...when safflower oil is used orally as part of the diet (6,13146,72238).

POSSIBLY SAFE ...when safflower oil is used topically for up to 8 weeks (95938). ...when safflower oil is administered intravenously in recommended doses by a health care professional. A specific safflower oil emulsion (Liposyn) 10% to 20% has been used intravenously for up to 2 weeks (72300,72301). ...when safflower yellow, a component of safflower flower, is administered intravenously and appropriately. Safflower yellow has been used with apparent safety in doses up to 150 mg daily for up to 5 weeks (94038,94041,102381).

CHILDREN: POSSIBLY SAFE
when safflower oil is administered intravenously in recommended doses by a healthcare professional. A specific safflower oil emulsion (Liposyn) 20% has been used intravenously in infants and children for up to 2 weeks (72284,72295). ...when safflower oil is used orally in medicinal amounts. Safflower oil 2.5 mL daily has been taken safely for 8 weeks (94042). There is insufficient reliable information available about the safety of safflower flower in children.

PREGNANCY: LIKELY SAFE
when safflower oil is used orally as part of the diet (6,13146,72238).

PREGNANCY: POSSIBLY SAFE
when safflower oil is administered intravenously in recommended doses by a healthcare professional (20529).

PREGNANCY: LIKELY UNSAFE
when safflower flower is used due to its abortifacient, menstrual stimulant, and uterine stimulant effects (11,12).

LACTATION: LIKELY SAFE
when safflower oil is used orally as part of the diet (6,13146,72238). There is insufficient reliable information available about the safety of safflower flower during lactation; avoid using.

Interactions with Drugs view details

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

AGMATINE

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, agmatine might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Details

Animal and in vitro research suggest that agmatine has mild hypoglycemic effects (94734).

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, agmatine might increase the risk of hypotension when taken with antihypertensive drugs.

Details

Animal research suggests that agmatine can modestly decrease heart rate and blood pressure (94734).

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

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

Avocado may antagonize the anticoagulant effects of warfarin.

Details

Avocado may antagonize the anticoagulant effects of warfarin; however, there has been only one case report of this interaction (667).

BRANCHED-CHAIN AMINO ACIDS (BCAA) (Glycyl-Alanyl-Lysine-L-Leucine, Glycyl-Alanyl-Lysine-L-Isoleucine, Glycyl-Alanyl-Lysine-L-Valine)

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, BCAAs might alter the effects of antidiabetes medications.

Details

Some evidence suggests that BCAAs might stimulate insulin release (10105,10110,10113,10114,10118). However, a small clinical study in adults with liver cirrhosis and high nocturnal levels of blood glucose suggests that BCAAs might increase blood glucose levels (103348).

LEVODOPA

Interaction Rating = Major Do not take this combination.

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

BCAAs in large doses can reduce the effects of levodopa.

Details

BCAAs may compete with levodopa for transport systems in the intestine and brain and decrease the effectiveness of levodopa (66,2719). Small clinical studies how that concomitant ingestion of protein or high doses of leucine or isoleucine (100 mg/kg) and levodopa can exacerbate tremor, rigidity, and the "on-off" syndrome in patients with Parkinson disease (3291,3292,3293,3294).

None known.

CONJUGATED LINOLEIC ACID (CLA) (Conjugated Linoleic Acid)

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

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

Details

Some clinical evidence suggests that intake of CLA reduces platelet aggregation by approximately 10% (45607). The clinical significance of this effect is unclear.

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

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

Details

Animal research suggests that a particular form of CLA reduces systolic blood pressure (45081). Also, some clinical research shows that CLA enhances the blood pressure-lowering effects of ramipril, an antihypertensive drug (45569).

RAMIPRIL (ALTACE)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, taking black seed with ramipril might increase the risk of hypotension.

Details

Some clinical research shows that CLA enhances the blood pressure-lowering effects of ramipril (45569).

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

High doses of safflower oil might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.

Details

Small clinical studies show that taking safflower oil, approximately 55 grams daily for 2-3 weeks, decreases platelet aggregation (72241,72303). However, taking lower doses of safflower oil, such as 5 grams daily for 4 weeks, does not seem to affect platelet function (66267). In one case report, a 74-year-old male stabilized on warfarin developed urinary tract bleeding and an elevated INR after taking a safflower extract 20 grams daily for 14 days (95939).

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, safflower oil might alter the effects of antidiabetes drugs.

Details

Some clinical research shows that taking safflower oil 10 grams daily for 3 weeks can increase fasting blood glucose in patients with type 2 diabetes (13146). However, clinical research in patients with metabolic syndrome with or without impaired glucose tolerance shows that taking safflower oil 8 grams daily for 12 weeks reduces fasting glucose levels by around 8 mg/dL (108889). Some clinical research also shows that taking safflower oil 8 grams daily for 16 weeks does not affect fasting glucose levels in patients with type 2 diabetes (94039).

WARFARIN

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, safflower oil might increase the risk of bleeding when taken with warfarin.

Details

In one case report, a 74-year-old male stabilized on warfarin developed urinary tract bleeding and an elevated INR after taking a safflower extract 20 grams daily for 14 days (95939).

Report an Adverse Reaction to Best BCAA Snow Cone

Adverse Effects view details

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

AGMATINE

General ...Orally, agmatine seems to be well tolerated when used in medicinal amounts, short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, nausea.

Gastrointestinal ...Orally, agmatine has been reported to cause diarrhea, dyspepsia, and nausea in two small clinical studies (94736,94742). Mild-to-moderate diarrhea and nausea were reported in 3 out of 24 patients taking agmatine sulfate 3.56 grams daily. These adverse effects appeared within 2-3 days of therapy and resolved upon treatment discontinuation (94736).

General ...Orally, avocado has been generally well tolerated in clinical research.
Most Common Adverse Effects:
Topically: A cream containing avocado oil in combination with vitamin B12 can cause itching.
Serious Adverse Effects (Rare):
Orally: Avocado may lead to allergic cross-sensitivity in latex sensitive patients. While rare, avocado can cause acute food protein-induced enterocolitis syndrome (FPIES), a food hypersensitivity reaction characterized by excessive vomiting and diarrhea.

Dermatologic ...Topically, a cream containing avocado oil in combination with vitamin B12 can cause itching when applied initially, but itching appears to diminish with continued use (14909). Orally, avocado may cause skin rash (112436).

Gastrointestinal ...Orally, avocado can cause acute food protein-induced enterocolitis syndrome (FPIES). This is a rare, delayed, non-IgE-mediated gastrointestinal food hypersensitivity reaction most often reported in infants and young children. Symptoms of FPIES include excessive vomiting within 1-4 hours of avocado consumption and diarrhea. Treatment is generally supportive in nature, including oral or intravenous rehydration, along with avoidance of avocado (100938). There have also been reports of gastrointestinal upset including gas, bloating, and diarrhea due to daily avocado consumption, though it is possible that these symptoms were due to E. coli infection (112436).

Immunologic ...Orally, avocado may lead to type I hypersensitivity reactions in people who are allergic to latex (6197,7853,25216,33248,33253,33254). While rare, avocado can also cause acute food protein-induced enterocolitis syndrome (FPIES). This is a delayed, non-IgE-mediated gastrointestinal food hypersensitivity reaction most often reported in infants and young children. Symptoms of FPIES include excessive vomiting within 1-4 hours of avocado consumption and diarrhea. Many infants and children who experience FPIES after eating avocado will have the same reaction to other foods, such as milk, oat, and rice (100938).

BRANCHED-CHAIN AMINO ACIDS (BCAA) (Glycyl-Alanyl-Lysine-L-Leucine, Glycyl-Alanyl-Lysine-L-Isoleucine, Glycyl-Alanyl-Lysine-L-Valine)

General ...Orally or intravenously, BCAAs are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, diarrhea, nausea, vomiting.
All routes of administration: High doses can lead to fatigue and loss of motor coordination.

Cardiovascular ...Orally, a single case of hypertension following the use of BCAAs has been reported (37143).

Dermatologic ...Orally, a single case of skin blanching following the use of BCAAs has been reported (681). It is not known if this effect was due to use of BCAAs or other factors.

Gastrointestinal ...Orally, BCAAs can cause nausea, vomiting, diarrhea, and abdominal distension. Nausea and diarrhea has been reported to occur in about 10% of people taking BCAAs (10117,37143,92643,97531).

Neurologic/CNS ...Orally and intravenously, BCAAs can cause fatigue and loss of motor coordination due to increased plasma ammonia levels (693,694,10117). Short-term use of 60 grams of BCAAs containing leucine, isoleucine, and valine for 7 days in patients with normal metabolic function seems to increase levels of ammonia, but not to toxic plasma levels (10117). However, liver function should be monitored with high doses or long-term use (10117). Due to the potential of increased plasma levels of ammonia and subsequent fatigue and loss of motor coordination, BCAAs should be used cautiously before or during activities where performance depends on motor coordination (75). Orally, BCAAs may also cause headache, but this has only been reported in one clinical trial (681).

General ...Orally and topically, coconut oil is generally well tolerated.
Most Common Adverse Effects:
Orally: Increased cholesterol levels.
Serious Adverse Effects (Rare):
All routes of administration: Allergic reactions, including anaphylaxis, in sensitive individuals.

Cardiovascular ...Due to its high saturated fat content, there has been some speculation that consuming coconut oil might increase cholesterol levels and the risk of cardiovascular disease. Several population and clinical studies have found that consuming coconut oil increases total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol in some patients (12361,14407,17935,17940,94451,94452,99103,101877,101879,106489,106494). In patients with normal to high cholesterol levels, consuming a daily diet providing 30% to 36% of calories from fat, of which 46% to 66% is from coconut oil, for 4-12 weeks increases total cholesterol by about 12-15 mg/dL, low-density lipoprotein (LDL) cholesterol by about 9-12 mg/dL, and HDL cholesterol by 3-6 mg/dL when compared to a diet containing vegetable oils, especially those rich in polyunsaturated fatty acids (17935,94451,94452,101877,106489). In some cases, these cholesterol effects are similar to those seen in patients consuming a similar diet containing butter or beef fat (12361,17935,94451,99103,101879). Despite the potential effects of coconut oil on cholesterol levels, population research has not found an association with coconut oil consumption and risk of adverse cardiovascular events such as myocardial infarction or angina (14407,96205). Advise patients not to rely on coconut oil as a "healthy" alternative to other saturated fats.

Dermatologic ...In one case report, a 6-year-old child developed urticaria and hives from applying coconut oil to the skin. The child had been exposed to coconut oil consistently since 2 weeks of age, indicating sensitization over the course of regular exposure (95806). In clinical research, one patient reported localized pruritus immediately after applying a combination of coconut oil, anise oil, and ylang ylang (13483). It is unclear if this event was due to coconut oil, other ingredients, or the combination. Also, it is possible that this was an idiosyncratic event.

Gastrointestinal ...Orally, diarrhea and gastroenteritis have been reported rarely (101877).

Hepatic ...Orally, taking virgin coconut oil in the diet for 28 days modestly increased levels of liver enzymes in patients with coronavirus disease 2019 (COVID-19). However, it is unclear if this was due to the coconut oil or to the illness (107664).

Immunologic ...Several cases of allergic reactions have been reported for patients who consumed coconut fruit. In some of the cases, the patients were previously diagnosed with sensitivity to other tree nuts, including peanuts, so cross-sensitivity is suspected. In a separate case report, a 17-year-old male was found to be sensitized to both coconut and buckwheat, indicating a possible cross-sensitivity between the two allergens (95808). In other cases, the patients did not show sensitivity to any other allergens, so the patients were considered to have a single allergy to coconut fruit (12359,12360).
Because coconut oil is derived from coconut fruit, ingestion of coconut oil may theoretically cause allergic reactions in patients with confirmed allergy to coconut fruit. In one case report, a 6-year-old child who had previously experienced urticaria and hives from applying coconut oil to the skin experienced throat swelling and anaphylaxis after eating food containing coconut, indicating a sensitivity to both the fruit and the oil via both topical application and ingestion (95806). However, allergic reactions to coconut appear to occur significantly less often than allergies to other food items such as wheat, milk, soy, or peanut (14408).

CONJUGATED LINOLEIC ACID (CLA) (Conjugated Linoleic Acid)

General ...Orally, CLA is well tolerated when found in foods. When taken in medicinal amounts, CLA seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, flatulence, loose stools, and nausea.
Serious Adverse Effects (Rare) :
Orally: Cases of hepatotoxicity have been reported.

Cardiovascular ...Some preliminary clinical research suggests that the t10,c12 isomer of CLA can decrease high-density lipoprotein (HDL) cholesterol levels (2821). This isomer of CLA, as well as a mixture of CLA isomers, seems to increase plasma triglyceride levels, the ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol, and the ratio of total cholesterol to HDL cholesterol (45148,45468), although not all research has identified these effects (107475).
A meta-analysis of 6 randomized, controlled trials shows that administration of CLA in individuals who are overweight or obese significantly increases lipoprotein (a) levels, a value associated with increased risk of cardiovascular disease. Subgroup analyses suggest this increase is more prominent in trials that are longer than 6 months in duration and with CLA doses of at least 3.5 grams daily (107475).

Endocrine ...Orally, CLA has been shown to increase insulin resistance and glucose concentrations, as well as decrease insulin sensitivity in some patients, including obese individuals or patients with type 2 diabetes (2821,13026,45145,45152,45513). Some evidence suggests that this effect is isomer-specific and occurs with only the t10,c12 isomer (2821,13026), while other evidence shows that decreased insulin sensitivity may also occur with the c9,t11 isomer or with a 50:50 mixture of c9,t11 and t10,c12 isomers (45145,45152).

Gastrointestinal ...Orally, the most common adverse effect reported with CLA is gastrointestinal upset including diarrhea, constipation, nausea, loose stools, dyspepsia, bloating, and flatulence (3153,4947,45280,45705,45730,111056). Esophageal irritation was reported in one patient who bit open and swallowed a capsule containing CLA (45577).

Hepatic ...Orally, clinical research shows that CLA 3 grams daily for 12 weeks does not affect liver outcome measures (105809). However, there are at least two case reports of hepatotoxicity. Asthenia, jaundice, and pruritus were reported in a 46-year-old female who consumed CLA for two weeks. Abnormal liver enzyme levels returned to normal following discontinuation of CLA supplementation (45483). Hepatotoxicity, presenting as fulminant hepatitis and characterized by anorexia, nausea, jaundice, choluria, and hepatic encephalopathy requiring liver transplantation has also been reported in a 63-year-old female taking a CLA-containing weight-loss supplement for one month (91589).

Musculoskeletal ...Orally, CLA has been reported to cause back ache in one individual in one clinical trial (45787).

Neurologic/CNS ...Orally, CLA may cause headache or fatigue (3153,45787). In one case report, a 50-year-old female presented with headache and subarachnoid hemorrhage due to reversible cerebral vasoconstriction syndrome (RCVS) after taking a combination product containing green tea, L-carnitine, and CLA for one week. At 28 days after discontinuation of the combination product and surgery, angiography showed complete regression of vascular restrictions (97007). It is unclear if this adverse effect was due to CLA, another ingredient in the product, or a combination of ingredients.

Other ...Orally, CLA has been reported to cause halitosis in one patient in one clinical trial (45839).

General ...Orally and intravenously, safflower oil seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Liver failure.

Dermatologic ...Intravenously, safflower yellow, a constituent of safflower flower, can cause skin rash (94038,94041). In one case, adjusting the rate of the drip improved the rash (94041).

Hepatic ...Orally, safflower oil has been associated with liver failure. There are at least 7 case reports of acute liver failure requiring liver transplant that are probably associated with over-use of safflower oil, usually for weight loss purposes. However, it is not clear what dose or duration of safflower use led to liver failure in these cases (99138).

Immunologic ...Safflower can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

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