| Ingredients | Each 5.4 g Scoop |
|---|---|
| 294.54 mg | |
| 49.09 mg | |
| 317.45 mg | |
| 1191.2 mg | |
| 497.45 mg | |
| 98.18 mg | |
|
(LPA)
|
199.64 mg |
| 278.18 mg | |
| 1.96 mg | |
| 327.27 mg |
Acacia Gum PlantPart: gum, Beta-Carotene, Citric Acid, Malic Acid, Stevia Genus: Stevia, Natural Flavors, Pineapple Flavor, Natural, Maltodextrin
In 2004, Canada began regulating natural medicines as a category of products separate from foods or drugs. These products are officially recognized as "Natural Health Products." These products include vitamins, minerals, herbal preparations, homeopathic products, probiotics, fatty acids, amino acids, and other naturally derived supplements.
In order to be marketed in Canada, natural health products must be licensed. In order to be licensed in Canada, manufacturers must submit applications to Health Canada including information about uses, formulation, dosing, safety, and efficacy.
Products can be licensed based on several criteria. Some products are licensed based on historical or traditional uses. For example, if an herbal product has a history of traditional use, then that product may be acceptable for licensure. In this case, no reliable scientific evidence is required for approval.
For products with non-traditional uses, some level of scientific evidence may be required to support claimed uses. However, a high level of evidence is not necessarily required. Acceptable sources of evidence include at least one well-designed, randomized, controlled trial; well-designed, non-randomized trials; cohort and case control studies; or expert opinion reports.
Finished products licensed by Health Canada must be manufactured according to Good Manufacturing Practices (GMPs) as outlined by Health Canada.
Below is general information about the effectiveness of the known ingredients contained in the product Muscle Matrix. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Muscle Matrix. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
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 the amounts found in foods.
POSSIBLY SAFE ...when used orally in larger amounts, short-term. L-histidine has been used with apparent safety in doses of up to 4 grams daily for up to 12 weeks (2347,2353,96311,108621), or in doses of up to 8 grams daily for up to 4 weeks (108620).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in the amounts found in foods.
There is insufficient reliable information available about the safety of histidine when used in larger amounts during pregnancy or lactation.
POSSIBLY SAFE ...when used orally and appropriately. L-arginine has been used safely in clinical studies at doses of up to 24 grams daily for up to 18 months (3331,3460,3595,3596,5531,5532,5533,6028,7815,7816)(8014,8473,13709,31943,91195,91196,91963,99264,99267,110380)(110387). A tolerable upper intake level (UL) for arginine has not been established, but the observed safe level (OSL) of arginine intake established in clinical research is 20 grams (31996). ...when used intravenously and appropriately. Parenteral L-arginine is an FDA-approved prescription product (15). ...when used topically and appropriately. L-arginine appears to be safe when 5 grams is applied as a topical cream twice daily for 2 weeks or when a dentifrice is used at a dose of 1.5% w/w for up to 2 years (14913,96806). ...when inhaled, short-term. L-arginine appears to be safe when inhaled twice daily at a dose of 500 mg for up to 2 weeks (96807).
CHILDREN: POSSIBLY SAFE
when used orally in premature infants and children (8474,32286,96803,97392,110391).
...when used intravenously and appropriately (97392). Parenteral L-arginine is an FDA-approved prescription product (15). ...when used topically, short-term. A dentifrice containing L-arginine appears to be safe when used at a dose of 1.5% w/w for up to 2 years in children at least 3.7 years of age (96806). ...when inhaled, short-term. L-arginine appears to be safe when inhaled twice daily at a dose of 500 mg for up to 2 weeks in children at least 13 years of age (96807).
CHILDREN: POSSIBLY UNSAFE
when used intravenously in high doses.
Parenteral L-arginine is an FDA-approved prescription product (15). However, when higher than recommended doses are used, injection site reactions, hypersensitivity reactions, hematuria, and death have occurred in children (16817).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
L-arginine 12 grams daily for 2 days has been used with apparent safety in pregnancy during the third trimester (11828). L-arginine 3 grams daily has been taken safely during the second and/or third trimesters (31938,110379,110382). ...when used intravenously and appropriately, short-term. Intravenous L-arginine 20-30 grams daily has been used safely in pregnancy for up to 5 days (31847,31933,31961,31978).
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in the amounts commonly found in foods. L-tryptophan is an essential amino acid that must be obtained from the diet. A typical diet in the United States supplies 0.5-2 grams of L-tryptophan daily (1146).
POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. L-tryptophan 5 grams daily for 21 days has been used with apparent safety (91460,97243). In 1989, L-tryptophan was linked to over 1500 reports of eosinophilia-myalgia syndrome (EMS) and several deaths (7067,8053,10085,11474,11478), leading to its removal from the U.S. market in 1990 (7067). The exact cause of EMS in patients taking L-tryptophan is unknown, but some evidence suggests that nearly all cases were due to contaminated L-tryptophan products from a single manufacturer (8050,8051,11477,11478). Under the Dietary Supplement Health and Education Act (DSHEA) of 1994, L-tryptophan is currently available and marketed as a dietary supplement. There is insufficient reliable information available about the safety of L-tryptophan when used orally, long-term.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods.
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts because it may cause respiratory depression in utero (1142).
Avoid using in amounts greater than those found in foods.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods.
There is insufficient reliable information available about the safety of larger medicinal amounts; avoid using.
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.
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.
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.
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.
Below is general information about the interactions of the known ingredients contained in the product Muscle Matrix. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, BCAAs might alter the effects of antidiabetes medications.
 Details
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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).
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Theoretically, concomitant use of L-arginine and ACE inhibitors may increase the risk for hypotension and hyperkalemia.
Details
Combining L-arginine with some antihypertensive drugs, especially ACE inhibitors, seems to have additive vasodilating and blood pressure-lowering effects (7822,20192,31854,31916). Furthermore, ACE inhibitors can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients (32213,32218). Theoretically, concomitant use of ACE inhibitors with L-arginine may increases the risk of hyperkalemia.
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Theoretically, concomitant use of L-arginine and ARBs may increase the risk of hypotension and hyperkalemia.
Details
L-arginine increases nitric oxide, which causes vasodilation (7822). Combining L-arginine with ARBs seems to increase L-arginine-induced vasodilation (31854). Furthermore, ARBs can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients (32213,32218). Theoretically, concomitant use of ARBs with L-arginine may increases the risk of hyperkalemia.
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Theoretically, concomitant use of L-arginine with anticoagulant and antiplatelet drugs might have additive effects and increase the risk of bleeding.
Details
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Theoretically, concomitant use of L-arginine might have additive effects with antidiabetes drugs.
Details
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Theoretically, concomitant use of L-arginine and antihypertensive drugs may increase the risk of hypotension.
Details
L-arginine increases nitric oxide, which causes vasodilation (7822). Clinical evidence shows that L-arginine can reduce blood pressure in some individuals with hypertension (7818,10636,31871,32201,32167,32225,31923,32232,110383,110384). Furthermore, combining L-arginine with some antihypertensive drugs seems to have additive vasodilating and blood pressure-lowering effects (7822,20192,31854,31916).
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Theoretically, concurrent use of isoproterenol and L-arginine might result in additive effects and hypotension.
Details
Preliminary clinical evidence suggests that L-arginine enhances isoproterenol-induced vasodilation in patients with essential hypertension or a family history of essential hypertension (31932).
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Theoretically concomitant use of potassium-sparing diuretics with L-arginine may increases the risk of hyperkalemia.
Details
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Theoretically, concurrent use of sildenafil and L-arginine might increase the risk for hypotension.
Details
In vivo, concurrent use of L-arginine and sildenafil has resulted in increased vasodilation (7822,8015,10636). Theoretically, concurrent use might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported (105065).
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Theoretically, concomitant use of L-arginine and testosterone might have additive effects.
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Theoretically, concomitant use of L-tryptophan with CNS depressants might cause additive sedative effects.
Details
Clinical research shows that L-tryptophan can cause fatigue and drowsiness (1143).
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Theoretically, combining L-tryptophan with serotonergic drugs might cause additive serotonergic effects.
Details
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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).
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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).
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Phenylalanine, especially in high doses, can reduce the effectiveness of levodopa.
Details
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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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Theoretically, threonine might decrease the effects of NMDA antagonists.
Details
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Below is general information about the adverse effects of the known ingredients contained in the product Muscle Matrix. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
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, histidine has been used with apparent safety in clinical research; however, a thorough evaluation of safety outcomes has not been conducted.
General
...Oral, intravenous, and topical L-arginine are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, nausea, diarrhea, headache, insomnia, flushing.
Intravenously: Excessively rapid infusion can cause flushing, headache, nausea and vomiting, numbness, and venous irritation.
Cardiovascular ...L-arginine taken orally by pregnant patients in a nutrition bar containing other antioxidants was associated with a 36% greater risk of palpitations when compared with a placebo bar (91197). It is unclear if this effect was due to L-arginine, other ingredients, or other factors.
Dermatologic ...Orally, arginine can cause flushing, rash, and hives (3460,32138,102587,104223). The skin reactions were likely of allergic etiology as oral L-arginine has been associated with eosinophilia (32138). In one case report, intravenous administration caused allergic reactions including urticaria, periorbital edema, and pruritus (11830). Excessively rapid infusion of L-arginine has caused flushing, local venous irritation, numbness. Extravasation has caused necrosis and superficial phlebitis (3330,16817).
Gastrointestinal
...Orally, L-arginine has been reported to cause nausea, diarrhea, vomiting, dyspepsia, gastrointestinal discomfort, and bloating (1363,31855,31871,31972,31978,32261,90198,91197,96811,99243)(102587,102592).
Orally, L-arginine has been reported to cause esophagitis in at least six adolescents. Symptoms, which included pain and dysphagia, occurred within 1-3 months of treatment in most cases (102588). There are at least two cases of acute pancreatitis possibly associated with oral L-arginine. In one case, a 28-year-old male developed pancreatitis after consuming a shake containing 1.2 grams of L-arginine daily as arginine alpha-ketoglutarate. The shake also contained plant extracts, caffeine, vitamins, and other amino acids. Although there is a known relationship between L-arginine and pancreatitis in animal models, it is not clear if L-arginine was directly responsible for the occurrence of pancreatitis in this case (99266).
Intravenously, excessively rapid infusion of L-arginine has been reported to cause nausea and vomiting (3330,16817).
Musculoskeletal ...Intravenous L-arginine has been associated with lower back pain and leg restlessness (32273). Orally, L-arginine has been associated with asthenia (32138).
Neurologic/CNS ...Orally, L-arginine has been associated with headache (31855,31955,32261,91197,102587,102592), insomnia, fatigue (102587,102592), and vertigo (32150,102592).
Oncologic ...In breast cancer patients, L-arginine stimulated tumor protein synthesis, which suggests stimulated tumor growth (31917).
Pulmonary/Respiratory ...When inhaled, L-arginine can cause airway inflammation and exacerbation of airway inflammation in asthma (121). However, two studies assessing oral L-arginine in patients with asthma did not detect any adverse airway effects (31849,104223).
Renal ...Intravenously, L-arginine has been associated with natriuresis, kaliuresis, chloruresis, and systemic acidosis (32225). Orally, L-arginine can cause gout (3331,3595).
Other ...Orally, L-arginine has been associated with delayed menses, night sweats, and flushing (31855).
General
...Orally, L-tryptophan is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, diarrhea, drowsiness, dry mouth, flatulence, headache, heartburn, lightheadedness, nausea, stomach pain, visual blurring, and vomiting.
Serious Adverse Effects (Rare):
Orally: L-tryptophan has been associated with the neurological disorder eosinophilia-myalgia syndrome (EMS). However, almost all cases were traced to L-tryptophan produced by a single manufacturer in Japan and are likely related to contamination.
Cardiovascular ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include cardiovascular symptoms such as myocarditis, arrhythmias, and palpitations (8053,11477).
Dermatologic ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include dermatological symptoms such as sclerodermiform skin changes, alopecia, and rash (8053,11477).
Gastrointestinal ...Orally, L-tryptophan can cause gastrointestinal side effects such as heartburn, stomach pain, belching and flatulence, nausea, vomiting, diarrhea, dry mouth, and anorexia (10853,99884).
Hematologic ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include hematologic symptoms such as eosinophilia (8053,11477).
Hepatic ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include hepatic symptoms such as hepatomegaly (8053,11477).
Musculoskeletal ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include musculoskeletal symptoms such as myalgia and inflammation of the joints and connective tissue (8053,11477).
Neurologic/CNS
...Orally, L-tryptophan can cause headache, lightheadedness, and ataxia (10853,99884).
In 1989, more than 1500 cases of the neurological disorder EMS were associated with oral L-tryptophan use in the US. About 95% of all EMS cases were traced to contaminated L-tryptophan produced by a single manufacturer in Japan (8054,10288,10289,11475,11476). In 1990, L-tryptophan was recalled in the U.S. and an FDA alert was put into force limiting the importation of all over-the-counter L-tryptophan products (7067,11477,11478). After the limitation of L-tryptophan products, the incidence of EMS dropped abruptly (11474). Symptoms of EMS associated with L-tryptophan use include intense eosinophilia; fatigue; myalgia; neuropathy; sclerodermiform skin changes; alopecia; rash; and inflammatory disorders affecting the joints, connective tissue, lungs, heart, and liver (8053,11477). Symptoms tend to improve over time, however some individuals may still experience symptoms up to 2 years after the onset of EMS and complete resolution of symptoms may not occur (8053,10287).
There is some evidence of an association between L-tryptophan-related EMS and the occurrence of chronic B-cell lymphocytic leukemia (8055).
Ocular/Otic ...Orally, L-tryptophan can cause side effects such as visual blurring (10853).
Pulmonary/Respiratory ...Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include respiratory symptoms such as dyspnea and cough (8053,11477).
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).
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).
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).
General ...Orally, threonine seems to be well tolerated.
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).
