EAAs Essential Amino Acids Kiwi-Stawberry [Discontinued] by Prime Nutrition Performance Series

POSSIBLY EFFECTIVE

• 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).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• 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.

(Read more about BRANCHED-CHAIN AMINO ACIDS (BCAA))

POSSIBLY EFFECTIVE

• Herpes labialis (cold sores). Most clinical research shows that oral lysine can prevent and treat herpes labialis. The benefits of topical lysine are unclear. Details: Despite one small clinical study that found no benefit (1116), most clinical research shows that taking oral lysine monohydrochloride 1000-1248 mg daily or 1000 mg three times daily reduces the recurrence of herpes labialis infections when compared with placebo (1114,1115,1118,1120,19390,19391). Also, small clinical studies show that taking oral lysine 1000 mg daily in up to two divided doses for up to 12 months or 1000 mg three times daily for 6 months reduces the severity and healing time of herpes labialis infections when compared with placebo (1119,1120). Topical lysine has also been studied in combination with other ingredients. A small, open-label study shows that applying a specific combination product containing lysine and zinc oxide plus 14 other ingredients (Super Lysine Plus +) topically every 2 hours for 11 days seems to decrease symptoms and duration of herpes lesions when compared with baseline (11051). The validity of this finding is limited by the lack of a comparator group. Also, it is unclear if any benefit is due to lysine, other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. Although there is interest in using oral lysine for improving athletic performance, there is insufficient reliable information about the clinical effects of lysine for this purpose.
• Canker sores. It is unclear if oral lysine is beneficial in patients with canker sores. Details: Preliminary clinical research shows that taking oral lysine 500 mg daily may be beneficial for preventing canker sores, and taking oral lysine 4000 mg daily may be beneficial for decreasing the duration of canker sores (19390).
• Child growth. Oral lysine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children aged 4-9 years old with idiopathic short stature shows that taking a combination oral solution containing lysine, inositol, and vitamin B12 10 mL twice daily along with moderate stretching exercises for 12 months increases height, growth velocity, and serum growth indicators and reduces height standard deviation scores when compared with control. However, the combination product does not impact body mass index or the ratio of bone age to chronological age when compared with control (112280). It is unclear if these findings are due to lysine, other ingredients, or the combination.
• Diabetes. It is unclear if oral lysine is beneficial in patients with diabetes. Details: One small clinical study shows that taking lysine hydrochloride 500 mg twice daily for 2 months does not affect fasting or postprandial blood glucose levels or glycated hemoglobin in patients with type 2 diabetes when compared a calcium phosphate control (19395).
• Diabetic foot ulcers. It is unclear if topical lysine is beneficial in patients with diabetic foot ulcers. Details: A small clinical study in adults with type 2 diabetes and grade 2 diabetic foot ulcers shows that applying topical lysine 15% cream twice daily with standard treatment for 8 weeks improves the rate of wound healing and skin color surrounding the wound, and also reduces ulcer size, depth, margins, undermining, edema, induration, granulation tissue, necrotic tissue amount and type, exudate type and amount, and epithelialization when compared with control (112279). The validity of the findings is limited by a lack of blinding and small sample size.
• Hypertension. Limited clinical research shows that oral lysine can reduce blood pressure in hypertensive patients who have deficient dietary lysine intake. Details: Preliminary clinical research in malnourished people in West Africa with deficient lysine intake shows that taking lysine orally 500 mg twice daily for 16 weeks reduces systolic blood pressure (SBP) when compared with placebo in those with hypertension at baseline. The mean SBP was reduced by 17 mmHg in males and 12 mmHg in females. Lysine supplementation did not affect SBP in people who were normotensive at baseline (104104).
• Hypertriglyceridemia. It is unclear if oral lysine is beneficial for patients with hypertriglyceridemia. Details: Preliminary clinical research shows that taking lysine 1 gram daily for 12 weeks, with or without vitamin B6 50 mg daily, does not affect body weight, triglyceride levels, or blood glucose levels when compared with placebo in males with hypertriglyceridemia. Furthermore, this dose of lysine, taken alone or in combination with vitamin B6, appears to slightly decrease high-density lipoprotein (HDL) cholesterol levels after 12 weeks when compared with placebo (90642).
• Muscle strength. Higher dietary intake of lysine seems to improve muscle strength in young under- or well-nourished males. Details: Preliminary clinical research in young, under- or well-nourished males shows that consuming lysine 80 mg/kg daily in the diet for 8 weeks improves muscle strength of the forearm by approximately 7.5% when compared with a diet containing lysine 25-40 mg/kg daily (90643).
• Pressure ulcers. A small study suggests that topical lysine may be beneficial for pressure ulcers. Details: A small clinical study in hospitalized adults shows that applying a specific cream containing lysine hyaluronate (Lys-HA, Lysial, Fatai-Nyl Srl; Jasper LLC) topically with dressing changes once daily for one week, then once every 2 days for one week, reduces pressure ulcer size when compared with a cream containing sodium hyaluronate. The effect appears to be greater in patients with more advanced (stage 3) ulcers compared to less advanced (stage 1) ulcers (90641).
• Schizophrenia. Large doses of oral lysine seem to improve schizophrenia symptoms in patients taking antipsychotic medications. Details: Clinical research in people with schizophrenia not controlled by risperidone shows that taking L-lysine 2 grams three times daily for 8 weeks improves symptoms by approximately 34% when compared with placebo. Negative and psychopathologic symptoms appear to improve the most (90645). In patients stabilized on antipsychotic medications, preliminary clinical research suggests that taking L-lysine 6 grams once daily for 4 weeks improves positive symptoms of schizophrenia, particularly delusions and suspiciousness/persecution, when compared with baseline. However, this improvement was not significant when compared with placebo (90644).
• Stress. Limited clinical research in economically disadvantaged populations shows that fortifying wheat with lysine may reduce stress and anxiety. Details: Preliminary clinical research shows that consuming wheat that has been fortified with lysine 4.2 grams/kg reduces stress in females and reduces anxiety in males in economically disadvantaged populations that typically consume cereal-based diets when compared with control (19394). More evidence is needed to rate lysine for these uses.

(Read more about LYSINE)

POSSIBLY EFFECTIVE

• Neural tube birth defects. High dietary intake of methionine during pregnancy seems to reduce the risk of neural tube birth defects. Details: Population research has found that higher dietary intake of methionine during pregnancy is associated with a reduced risk of neural tube defects when compared with lower dietary intake (63117,63135).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acetaminophen poisoning. It is unclear if oral methionine is beneficial in patients with acute acetaminophen poisoning. Details: Observational research has found that taking methionine 2.5 grams every 4 hours for a total of four doses, starting within 10 hours of acetaminophen overdose, may have similar efficacy to acetylcysteine for preventing liver damage and death (2413).
• Allergic rhinitis (hay fever). Although there has been interest in using oral methionine for seasonal allergies, there is insufficient reliable information about the clinical effects of methionine for this purpose.
• Asthma. Although there has been interest in using oral methionine for asthma, there is insufficient reliable information about the clinical effects of methionine for this purpose.
• Breast cancer. It is unclear if high dietary intake of methionine reduces the risk of breast cancer. Details: A meta-analysis of observational studies suggests that higher dietary intake of methionine is associated with a 6% lower risk of breast cancer, especially for postmenopausal adults, when compared with lower intake. Increasing dietary intake of methionine by 1 gram daily may be associated with a 4% reduction in the risk of breast cancer. These results appear to be more prominent in postmenopausal adults when compared with premenopausal adults; however, this could have been by chance due to the small number of studies that assessed premenopausal adults (94093). A more recent meta-analysis, including 4 additional observational studies, suggests that there is no significant association between methionine intake and breast cancer risk. This finding is largely influenced by inclusion of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort study, which analyzed data from over 300,000 subjects and found no relationship between methionine intake and breast cancer risk (111416).
• Cisplatin-associated ototoxicity. It is unclear if oral D-methionine prevents cisplatin-associated ototoxicity. Details: A small clinical study in adults with cancer receiving cisplatin shows that taking D-methionine 100 mg/kg one hour prior to chemotherapy for up to 5 cycles prevents shifts in the hearing threshold at all four tested frequencies, compared with shifts occurring at three of the four tested frequencies in those receiving placebo (108039). The validity of these findings is limited by the lack of statistical comparison between groups.
• Colorectal cancer. It is unclear if high dietary intake of methionine reduces the risk of colorectal cancer. Details: A meta-analysis of observational research has found that higher dietary intake of methionine is associated with an 11% lower risk of colorectal cancer, a 23% lower risk of colon cancer, and a 12% lower risk of rectal cancer, when compared with lower intake of methionine. Increasing dietary intake of methionine by 1 gram daily is associated with a 11% reduction in the risk of colorectal cancer. Subgroup analyses have shown a significant inverse relationship between risk of colorectal cancer and dietary methionine intake in patients followed for at least 13.3 years, in Western populations, and in males (94094). There is some evidence that high dietary intake of methionine and folate might have a synergistic effect in decreasing the risk of colon cancer, especially in those with a family history of colon cancer and in those who consume large amounts of alcohol (9325,9326).
• Genital herpes. Oral L-methionine has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: A small clinical study in patients with genital warts caused by herpes simplex virus (HSV) shows that taking acyclovir 200 mg five times daily for 5 days followed by 4 capsules of a combination product providing a total daily dose of L-methionine 200 mg, coenzyme Q10 50 mg, vitamin E 50 mg, and selenium 50 mcg for 90 days increases the rate of skin reepithelization by approximately 2 days and decreases the incidence of relapse when compared with acyclovir alone. Patients receiving combination therapy had a relapse rate of 13%, compared with a rate of 43% with acyclovir alone (94091).
• Herpes zoster (shingles). Oral L-methionine has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: A small clinical study in patients with herpes zoster shows that taking acyclovir 800 mg five times daily for 10 days followed by 4 capsules of a combination product providing a total daily dose of L-methionine 200 mg, coenzyme Q10 50 mg, vitamin E 50 mg, and selenium 50 mcg for 90 days increases the rate of skin reepithelization by approximately 2 days, decreases the incidence of relapse, and decreases postherpetic neuralgia pain when compared with acyclovir alone. Patients receiving combination therapy had a relapse rate of 7%, compared with a rate of 44% with acyclovir alone (94091).
• Human papillomavirus (HPV). It is unclear if oral methionine is beneficial for the treatment of HPV lesions or for reducing the incidence of relapse. Details: A clinical study in patients aged 14 years or older with cutaneous warts caused by HPV shows that receiving conventional therapy in combination with one capsule of a product containing methionine, echinacea, inulin, taurine, vitamin A, vitamin C, coenzyme Q10, vitamin B3, zinc gluconate, and probiotics (Immuno Skin Plus tablets, Morgan Pharma S.r.l) daily for 20 days each month for 4 months reduces the number of warts at 6 months by about 5, with complete remission achieved in 86% of patients. The group receiving conventional therapy alone had a reduction in the number of warts by about 3, with complete remission achieved in 55% of patients. Conventional therapy consisted of either liquid nitrogen cryotherapy or topical therapy with salicylic acid 15% and lactic acid 15%. These findings are limited by the fact that patients in the combination therapy group had more warts at baseline when compared with those receiving conventional therapy alone (94092). Another small clinical study in patients with skin warts caused by HPV shows that cryotherapy followed by taking 4 capsules of a product containing a total dose of L-methionine 200 mg, coenzyme Q10 50 mg, vitamin E 50 mg, and selenium 50 mcg daily for 180 days increases the rate of complete recovery and decreases the incidence of relapse when compared with cryotherapy followed by placebo. At 180 days, 56% of patients in the active group experienced complete recovery, compared with 44% in the placebo group, and 30% of patients in the active group experienced a relapse, compared with 41% in the placebo group (94091). It is unclear if these effects are due to methionine, other ingredients, or the combination.
• Menopausal symptoms. It is unclear if oral L-methionine is beneficial for reducing hot flashes. Details: Preliminary clinical research in postmenopausal adults experiencing at least 5 hot flashes daily for the prior two months shows that taking L-methionine 1 gram twice daily for 12 weeks, then 2 grams twice daily for 8 weeks, does not improve hot flashes when compared with placebo (94090).
• Pancreatitis. Oral methionine has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: A meta-analysis of eight randomized and nonrandomized clinical studies in patients with chronic or recurrent acute pancreatitis shows that taking a combination of methionine, selenium, vitamin E, vitamin C, and beta-carotene reduces pain when compared with placebo. However, when the two nonrandomized studies were excluded, the significant reduction in pain was lost. Daily doses of individual components studied included methionine 1.6-2.88 grams, selenium 300-600 mcg, vitamin E 188-280 mg, vitamin C 540-720 mg, and beta-carotene 12-54 mg. The study durations ranged from 10 weeks to 12 months (94095). The validity of these findings is limited by the heterogeneity of the included studies.
• Parkinson disease. Although there has been interest in using oral methionine for Parkinson disease, there is insufficient reliable information about the clinical effects of methionine for this purpose.
• Urinary tract infections (UTI). Oral methionine has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: A low-quality observational study in patients with symptomatic UTI and culture-confirmed bacteriuria during pregnancy has found that taking a specific combination of methionine 800 mg, Hibiscus sabdariffa extract 200 mg, and Boswellia serrata 200 mg (Acidif Plus, Biohealth S.r.l) daily for one week increases the rate of negative urine cultures to 70% and symptom resolution to 63%, compared with 43% and 46%, respectively, in patients who increased fluid intake but did not take the combination product (97263). The validity of these findings is limited by the fact that the study groups were not comparable at baseline.
• Wound healing. Although there has been interest in using oral methionine for wound healing, there is insufficient reliable information about the clinical effects of methionine for this purpose. More evidence is needed to rate methionine for these uses.

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POSSIBLY EFFECTIVE

• Vitiligo. Small clinical studies suggest that oral or topical L-phenylalanine, when used in combination with UVA light, might modestly improve symptoms in adults and children with vitiligo. Details: Taking L-phenylalanine, as 50 mg/kg two to three times weekly or up to 100 mg/kg once daily orally for up to 3 months, or applying L-phenylalanine 10% cream topically, both in combination with UVA light exposure, seem to be effective for treating vitiligo in adults (2461,2463,2464,2466) and in children (2467).

POSSIBLY INEFFECTIVE

• Attention deficit-hyperactivity disorder (ADHD). Taking phenylalanine orally does not seem to be beneficial for ADHD. Details: Some research suggests that patients with ADHD have lower levels of amino acids such as phenylalanine (9948), but neither D-phenylalanine nor DL-phenylalanine appear to have any sustained effect on ADHD symptoms (9950,9951).
• Pain (chronic). Taking D-phenylalanine orally does not seem to be beneficial for chronic pain. Details: A small clinical study in patients with chronic pain of various etiologies shows that taking D-phenylalanine 250 mg four times daily for 4 weeks does not reduce pain when compared with placebo (2459). Additionally, a small clinical study in adults with chronic low back pain shows that taking D-phenylalanine 4 grams orally as a single dose prior to acupuncture does not enhance analgesic effects when compared with acupuncture alone (2456).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. It is unclear if topical undecylenoyl phenylalanine is beneficial for age spots. Details: Preliminary clinical research shows that applying undecylenoyl phenylalanine 2% cream to age spots, also known as solar lentigines, twice daily for 12 weeks significantly reduces the number of spots or their pigmentation when compared with controls (92704).
• Alcohol use disorder. Oral DL-phenylalanine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients experiencing alcohol withdrawal symptoms shows that taking a combination of DL-phenylalanine 300 mg, L-glutamine 150 mg, and 5-HTP 5 mg orally daily for 40 days improves depression, hostility, and physical symptoms caused by psychological distress, when compared with placebo (30100).
• Depression. It is unclear if oral phenylalanine is beneficial in patients with depression. Details: Older clinical research conducted prior to 1985 suggests that taking L-phenylalanine 250 mg orally or intravenously daily for 14-96 days in combination with selegiline, or DL-phenylalanine 50-200 mg orally daily for 15-30 days, might improve symptoms of depression (2468,2469,68795,68825). However, taking D-phenylalanine, 50-100 mg daily for 15 days, does not seem to provide any benefit (68795,68830).
• Multiple sclerosis (MS). Oral L-phenylalanine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that treatment with Cari Loder's regimen, which includes oral L-phenylalanine and lofepramine, plus intramuscular (IM) vitamin B12 for 24 weeks, does not improve disability in patients with MS when compared with placebo plus IM vitamin B12 (68796).
• Obesity. It is unclear if oral L-phenylalanine is beneficial in obese or overweight patients. Details: Preliminary clinical research in females with overweight or obesity shows that taking L-phenylalanine 5 grams or 10 grams orally 20 minutes before meals twice daily does not reduce energy intake or improve satiety when compared with placebo (92705).
• Osteoarthritis. Although there is interest in using oral phenylalanine for osteoarthritis, there is insufficient reliable information about the clinical effects of phenylalanine for this condition.
• Pain (acute). It is unclear if oral D-phenylalanine is beneficial for acute pain. Details: Preliminary clinical research shows that taking D-phenylalanine 2-4 grams orally as a single dose 30 minutes prior to tooth extraction modestly enhances the analgesic effects of acupuncture when compared with acupuncture alone (2456).
• Parkinson disease. Although there is interest in using oral phenylalanine for Parkinson disease, there is insufficient reliable information about the clinical effects of phenylalanine for this condition.
• Rheumatoid arthritis (RA). Although there is interest in using oral phenylalanine for RA, there is insufficient reliable information about the clinical effects of phenylalanine for this condition. More evidence is needed to rate phenylalanine for these uses.

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POSSIBLY INEFFECTIVE

• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Taking threonine 2 grams/day orally for 7 days, or 4 grams/day orally, divided into two or four doses, for up to 12 months does not seem to slow the progression of early-stage ALS or reduce symptoms (681,12057,60069). There is also concern that threonine might actually worsen pulmonary function in these patients. The decline in forced vital capacity (FVC) associated with threonine therapy was about 2.5 times greater than that with placebo (681).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Familial spastic paraparesis (FSP). There is preliminary evidence that taking threonine 1.5 grams to 2 grams orally, three times daily, might improve some measures of motor impairment and spasticity in people with familial spastic paraparesis. However, the improvement does not seem to be clinically significant (12059).
• Multiple sclerosis (MS). Preliminary clinical evidence shows that taking threonine 2.5 grams orally three times daily for 8 weeks does not significantly reduce spasticity in people with inactive or slowly progressive MS (60073).
• Spasticity. Preliminary clinical evidence shows that taking threonine 2 grams orally three times daily for 2 weeks might help improve leg muscle tone in people with spasticity arising from spinal cord injuries. However, methodological problems limit the usefulness of this finding (12056). More evidence is needed to rate threonine for these uses.

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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).

(Read more about BRANCHED-CHAIN AMINO ACIDS (BCAA))

POSSIBLY SAFE ...when used orally in doses up to 3000 mg daily for up to one year (1114,1119,1120,90642,104104), or up to 6000 mg daily for up to 8 weeks (90644,90645). ...when used topically and appropriately, short-term (11051).

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

(Read more about LYSINE)

LIKELY SAFE ...when used orally in amounts commonly found in food (94500).

POSSIBLY SAFE ...when used orally or intravenously and appropriately in medicinal amounts under the supervision of a healthcare professional (2410,2411,2413).

POSSIBLY UNSAFE ...when used orally or intravenously in excessive doses. Doses larger than 100 mg/kg should be avoided to prevent severe and potentially lethal cerebral effects (9339).

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (94500).

CHILDREN: POSSIBLY SAFE
when used intravenously and appropriately (9338).

CHILDREN: POSSIBLY UNSAFE
when used intravenously in infants receiving parenteral nutrition. In infants, blood methionine concentration can increase due to lower enzyme activity and inability to metabolize methionine. High levels of methionine can cause liver toxicity (9338).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food (94500). There is insufficient reliable information available about the safety of methionine in medical doses during pregnancy and lactation; avoid using.

(Read more about METHIONINE)

LIKELY SAFE ...when L-phenylalanine is consumed in amounts typically found in foods (11120).

POSSIBLY SAFE ...when L-phenylalanine is used orally in doses up to 100 mg/kg daily for up to 3 months (2463,2464,2466,2467,2469). ...when D-phenylalanine is used orally in doses up to 1 gram daily for up to 4 weeks, or as a single dose of 4-10 grams (2455,2456,2459,68795,104792). ...when DL-phenylalanine is used orally in doses up to 200 mg daily for up to 4 weeks (2468,68795,68825). ...when phenylalanine cream is applied topically, short-term (2461,92704).

PREGNANCY: LIKELY SAFE
when L-phenylalanine is consumed in amounts typically found in foods by pregnant patients with normal phenylalanine metabolism (2020,11120).

PREGNANCY: UNSAFE
when L-phenylalanine is consumed in amounts typically found in foods by pregnant patients with high serum phenylalanine concentrations, such as those with phenylketonuria (PKU). Serum levels of phenylalanine greater than 360 micromol/L increase the risk of birth defects (1402,11468). Experts recommend that patients with high phenylalanine serum concentrations follow a low phenylalanine diet for at least 20 weeks prior to conception to decrease the risk for birth defects (1402). There is insufficient reliable information available about the safety of L-phenylalanine when taken by mouth in large doses during pregnancy; avoid using. There is insufficient reliable information available about the safety of oral D-phenylalanine during pregnancy; avoid using.

LACTATION: LIKELY SAFE
when L-phenylalanine is consumed in amounts typically found in foods by breast-feeding patients with normal phenylalanine metabolism (2020,11120). There is insufficient reliable information available about the safety of L-phenylalanine when taken by mouth in medicinal amounts during lactation; avoid using. There is insufficient reliable information available about the safety of oral D-phenylalanine during lactation; avoid using.

(Read more about PHENYLALANINE)

LIKELY SAFE ...when used orally in food amounts. Threonine as L-threonine in doses of 7-14 mg/kg daily (about 0.5-1 gram daily) has been suggested to be the minimum amount required to maintain a positive nitrogen balance in humans and is generally considered to be safe (60072,94096).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Taking threonine in doses up to 4 grams daily for up to 12 months seems to be safe (681,12056,12057,12059,60069).

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

(Read more about THREONINE)

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).

(Read more about BRANCHED-CHAIN AMINO ACIDS (BCAA))

5-HT4 AGONISTS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, lysine may reduce the effects of 5-HT4 agonists.  Details Animal research suggests that L-lysine is a partial serotonin receptor 4 (5-HT4) antagonist and inhibits diarrhea induced by the 5-HT4 agonist, 5-hydroxytryptophane (19400).

(Read more about LYSINE)

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BACLOFEN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant intake of phenylalanine may reduce the intestinal absorption of baclofen.  Details Phenylalanine and baclofen share the same intestinal carrier for absorption; phenylalanine competitively inhibits the absorption of baclofen, reducing its plasma levels (23788).

LEVODOPA Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Phenylalanine, especially in high doses, can reduce the effectiveness of levodopa.  Details Phenylalanine competes with levodopa for carrier-mediated transport into the brain. The resulting reduction in levels of levodopa in the brain can exacerbate tremor, rigidity, and the "on-off" phenomenon in patients with Parkinson disease (3291,3294).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of L-phenylalanine and non-selective MAOIs might increase the risk of hypertensive crisis.  Details L-phenylalanine is metabolized to tyrosine (2052,9949). Some evidence suggests that L-phenylalanine, given with the non-selective MAOI pargyline, might prevent the elimination of tyramine, increasing the risk of hypertensive crisis (2021). However, this was not reported in a small number of patients when using L-phenylalanine with the partially selective MAO-B inhibitor, selegiline (2469).

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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).

(Read more about BRANCHED-CHAIN AMINO ACIDS (BCAA))

General ...Orally and topically, lysine is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, and dyspepsia.

Gastrointestinal ...Orally, lysine has been reported to cause diarrhea and abdominal pain, including dyspepsia (1114,1115,1116,1118,1120).

Renal ...There is one case report of oral lysine use associated with tubulointerstitial nephritis progressing to chronic renal failure in a 44-year old female (1121).

(Read more about LYSINE)

General ...Orally, methionine is well tolerated when used in amounts commonly found in foods. Intravenously, methionine is generally well tolerated.
Most Common Adverse Effects:
All ROAs: Dizziness, drowsiness, hypotension, irritability, and vomiting. Methionine may also cause headache, increased homocysteine levels, increased urinary calcium excretion, and leukocytosis.
Serious Adverse Effects (Rare):
All ROAs: Cerebral edema, hepatic encephalopathy. In infants, intravenous methionine has been linked to liver toxicity.

Cardiovascular ...Orally or intravenously, methionine can cause hypotension (9339,9340). High-dose methionine (75-100 mg/kg daily) may increase plasma concentrations of homocysteine, which is a risk factor for vascular disease (63112,63114,63115). However, a study of patients with type 2 diabetes and a history of cardiovascular disease (CVD) showed that methionine loading did not increase homocysteine concentrations, and that a cause-effect relationship between increased intake of methionine and endothelial dysfunction has not been clearly established (63110).

Gastrointestinal ...Orally or intravenously, methionine can cause vomiting (9339,9340).

Genitourinary ...Orally or intravenously, methionine may increase urinary calcium excretion (9340,63112,94095).

Hematologic ...Orally or intravenously, methionine may cause leukocytosis when used at a dose of 8-13. 9 grams daily for 4-5 days (9340).

Hepatic ...A single dose of 8 grams of methionine has reportedly caused hepatic encephalopathy in patients with cirrhosis (9340). Long-term use of methionine-containing parenteral nutrition solution has been linked to liver toxicity in infants (9338).

Neurologic/CNS ...Orally or intravenously, methionine can cause dizziness, drowsiness, headache, and irritability (9339,9340,94095).
A case of cerebral edema ultimately leading to death has been reported in a patient receiving methionine 100 mg/kg orally. The post-load plasma concentrations of methionine were substantially higher in this patient than those previously reported in humans receiving this usual oral loading dose, leading the authors to postulate that an overdose of methionine may have been administered erroneously. This can occur when plasma methionine levels rise above 3000 mcmol/L (9339). Another case of progressive cerebral edema associated with high methionine levels and betaine (N,N,N-trimethylglycine) therapy in a patient with cystathionine beta-synthase (CBS) deficiency has been reported (63119). The authors stated that the cerebral edema was most likely precipitated by the betaine therapy, but that the exact mechanism is uncertain.

Oncologic ...Although one case-control study of incident, histologically-confirmed gastric cancer has indicated that a diet rich in methionine, salt, and nitrite is associated with an increased risk of gastric cancer (2409), a large observational study that adjusted for multiple factors, including sodium intake, has found no association between high dietary intake of methionine and gastric cancer (108041).

(Read more about METHIONINE)

General ...Orally, L-phenylalanine and D-phenylalanine are generally well tolerated when used in typical doses.
Most Common Adverse Effects:
Orally: Anxiety, constipation, headache, heartburn, insomnia, nausea, and sedation.
Topically: Burning, erythema, and itching.

Cardiovascular ...One patient in a small case series developed extrasystoles after 10 days of treatment with DL-phenylalanine, but this resolved on the 12th day of treatment without discontinuing phenylalanine (68825).

Dermatologic ...Topically, erythema, itching, and burning have been reported in some patients using an undecylenoyl phenylalanine 2% cream for treatment of age spots (92704).

Gastrointestinal ...Orally, constipation, heartburn, and nausea has been reported in some patients taking phenylalanine (2463,68827,68829,68830).

Neurologic/CNS ...Orally, headaches, which are typically transient and do not require treatment or dosage reduction, have been reported during the first 10 days of treatment with L-, D-, and DL-phenylalanine (68795,68825,68827,68829). Transient vertigo has also been reported with D- and DL-phenylalanine (68795).
In patients with Parkinson disease, taking DL-phenylalanine, especially in high doses, interferes with levodopa transport into the brain, causing increased rigidity, tremor, and occurrence of the on-off phenomenon. Akinesia has been reported more rarely (3291,3292,3293,3294,68828). In patients with schizophrenia, taking a single dose of L-phenylalanine 100 mg/kg has been associated with worsening of medication-induced tardive dyskinesia (2457).

Psychiatric ...Orally, L-phenylalanine has been associated with anxiety, insomnia, and, more rarely, hypomania (68827,68829). DL-phenylalanine has been associated with fatigue and sedation (9951).

(Read more about PHENYLALANINE)

General ...Orally, threonine seems to be well tolerated. Some patients can experience minor gastrointestinal upset including diarrhea (12056). Other side effects reported in people who have taken threonine include headache, rhinorrhea, flatus, constipation, and skin rash. One patient had a two-fold increase in serum ammonia levels following administration of threonine 4 grams daily (681).

Dermatologic ...Orally, skin rash has been reported in people who have taken threonine (681).

Gastrointestinal ...Orally, some patients can experience minor gastrointestinal upset including diarrhea (12056). Other side effects reported in people who have taken threonine include flatus and constipation (681).

Neurologic/CNS ...Orally, headache has been reported in people who have taken threonine (681).

Pulmonary/Respiratory ...Orally, rhinorrhea has been reported in people who have taken threonine (681).

Other ...Orally, a two-fold increase in serum ammonia levels occurred in one patient following administration of threonine 4 grams daily (681).

(Read more about THREONINE)