L-Methionine 500 mg by Bluebonnet

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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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.

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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).

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