Methylcobalamin

Methylcobalamin

Methylcobalamin

Clinical overview

Use

dosage

The Dietary Reference Intake (DRI, also known as the recommended daily intake). [RDA]) for vitamin B12 is 2.4 µg/day.

Clinical studies with specific dosage recommendations for methylcobalamin are lacking. The dosage depends on the recommended dosages for vitamin B12. Limited studies have used high doses of methylcobalamin (1,500 mcg/day orally).

Contraindications

None identified.

Pregnancy/breastfeeding

Tolerable at usual dosages.

Interactions

Drugs thought to reduce the absorption of vitamin B12 include alcohol, aminosalicylic acid, chloramphenicol, colchicine, metformin, neomycin, and proton pump inhibitors.

Side effects

Vitamin B12 is well tolerated in the dosage contained in foods or dietary supplements. Gastrointestinal effects of methylcobalamin may include anorexia, diarrhea, headache, nausea, and vomiting.

toxicology

Specific toxicological studies are lacking. Vitamin B12 has long been used safely, even in high doses. At usual dosages, the cobalt and cyanide content is not considered toxicologically relevant.

source

Vitamin B12 is obtained from animal products (e.g. meat, fish, shellfish, poultry, eggs, milk, dairy products). Tempeh, made from fermented soybeans, contains the beneficial bacteria responsible for producing vitamin B12. Commercial forms of methylcobalamin are made in the laboratory by converting cyanocobalamin. Harvard 2005

Story

Early empirical work on the structure and function of cobalamins as coenzymes was carried out in the 1950s using vitamin B12-dependent bacteria. Beck 1990 Previously, Addison's anemia (pernicious anemia) was described and the involvement of intrinsic factor was recognized through experiments with regurgitated raw meat. The discovery of liver to treat pernicious anemia in the 1920s led to the Nobel Prize in Medicine, and in 1948 Karl Folkers and Alexander Todd identified cobalamin as an active ingredient in the liver. Olson 2001

Chemistry

Methylcobalamin is the methyl form of cobalamin, which is derived from hydroxycobalamin, either through chemical manipulation in the laboratory or in the body as a natural process. Cyano- and hydroxocobalamin are considered storage or transport forms of cobalamin, while methylcobalamin and deoxyadenosylcobalamin are the active forms involved in enzymatic reactions. Methylcobalamin is particularly involved in normal folic acid metabolism and the resulting maintenance of normal homocysteine ​​serum levels. Facts and comparisons 2011

The 4 cobalamins are often referred to together as vitamin B12 and are essential cofactors in the bone marrow and myeloid cells, where chromosome replication and cell division take place. Facts and comparisons 2011

Use and Pharmacology

Vitamin B12 deficiency

The prevalence of vitamin B12 deficiency in older Americans is estimated to be approximately 20%. (Andres 2010, Harvard 2005) A deficiency of vitamin B12 in the diet can arise from poor diet or in strict vegetarians who do not consume animal products. Elderly patients and people taking proton pump inhibitors experience a lack of stomach acid, which leads to poor digestion of the vitamin from animal products. People with a deficiency of intrinsic factor (also known as pernicious anemia), as well as people with severe gastrointestinal diseases with impaired small bowel function (e.g. Crohn's disease) or people who have had gastric bypass surgery may also have a vitamin B12 deficiency. (Harvard 2005, Ito 2010, McCaddon 2010, Stover 2010)

The deficiency can lead to subtle cognitive and neurological changes, as well as more severe anemia and dementia. (Ito 2010, McCaddon 2010, Stover 2010) Newborn development may also be affected in infants breastfed by mothers with vitamin B12 deficiency. (Harvard 2005, Pepper 2011)

Animal data

Specific data on the correction of methylcobalamin deficiencies in animals are lacking.

Clinical data

A vitamin B12 deficiency can be corrected by giving cobalamin. Usually either cyano- or hydroxocobalamin is used to restore normal levels. Clinical studies specifically evaluating methylcobalamin supplementation are lacking. However, there is no reason to assume a lack of effectiveness and there are reports of the therapeutic effectiveness of methylcobalamin. (Head 2006, Maladkar 2009, Sharma 2012)

The Academy of Nutrition and Dietetics (AND)'s 2016 Statement on Vegetarian Diets states that vitamin B12 intake is lower among vegetarians than non-vegetarians because it is not found in plant-based foods. Additionally, it is said that neither fermented soy products nor unfortified plant foods are reliable sources of vitamin B12. Pregnant and breastfeeding women, as well as infants breastfed by mothers with inadequate vitamin B12 intake, should receive vitamin B12 supplementation. Likewise, older vegetarian adults should use foods or supplements fortified with vitamin B12. Poor vitamin B12 status has been linked to an increased risk of dementia. (Melina 2016)(Melina 2016) A review of guidelines addressing nutrition, physical activity, and nutrient supplementation before and after bariatric surgery found one guideline that included micronutrient recommendations; the American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update: Micronutrients. Vitamin B12 supplementation was recommended for all patients following bariatric surgery following weight loss (Grade B, Stage 2) at an oral dose of 350 to 500 mg/day (disintegrating tablet, sublingual, liquid) or nasal spray according to the manufacturer's instructions. To treat postoperative deficiency, a dose of 1,000 mg/day was recommended until normal limits were reached, and then doses required to maintain normal values ​​were resumed (Grade B, Level 2). (Tabesh 2019)

Neuropathy

Animal data

In animal models of vitamin B12-related neuropathy, an ultra-high dose of methylcobalamin (500 µg/kg) resulted in the regeneration of motor neurons. (Head 2006)

Clinical data

Limited clinical trials have evaluated the effect of supplemental methylcobalamin on diabetic peripheral neuropathy as well as neuropathy associated with renal disease. Subjective measurements were reported to have improved. (Head 2006, Maladkar 2009)

Reversal of moderate cognitive impairment (dementia) was reported in an 83-year-old woman with oral methylcobalamin, but not hydroxocobalamin, even though B12 levels were within normal limits. Therapy was inspired by the VITACOG study and consisted of daily oral methylcobalamin (3,000 µg) and folic acid (1,200 µg). Two months later, her Mini Mental State Examination improved from 14 to 29 and her body mass index improved from 17.1 to 22.6 kg/m2. (Rietsema 2014)

The American Academy of Neurology (AAN) updated practice guideline for mild cognitive impairment (2018) states that there is insufficient evidence to support or refute the use of homocysteine-lowering B vitamins, including vitamin B12, in patients with mild cognitive impairment (very low). Level, Class II).(Petersen 2018) Additionally, the updated British Association for Psychopharmacology Consensus Statement on Clinical Practice with Antidementia Drugs (2016) advises against the use of vitamin B12, either alone or in combination with folic acid, for the treatment of dementia and dementia prevention based on Type I (Level A) evidence. (O'Brien 2017)

Vegetarian diet

Clinical diet

The Academy of Nutrition and Dietetics' updated position paper on vegetarian nutrition (2016) states that adequate nutrition can be ensured through a well-planned vegetarian diet containing legumes. Therapeutic vegetarian diets help maintain a healthy weight and body mass index and are associated with a reduction in the risk of cardiovascular disease and type 2 diabetes. Vitamin B12 is not found in plant foods. Therefore, it is important that vegetarians (especially vegans) regularly consume reliable sources of vitamin B12, such as B12-fortified foods or supplements, to prevent deficiency. Special consideration for vitamin B12 is required in pregnant vegetarians as well as in children and older adults. (Melina 2016)

Other uses

Animal studies and clinical data suggest that parenteral vitamin B12 therapy has a role in the care of the critically ill, particularly in shock. However, clinical studies and information specific to methylcobalamin are lacking. (Manzanares 2010)

A systematic review found little evidence for vitamin B12 supplementation to reduce the risk of diabetes or cardiovascular disease. (Pezzini 2007, Rafnsson 2011) A 2013 meta-analysis that included 15 studies and 1,106 diabetic patients found combination therapy for 2 to 4 weeks with intravenous (IV) alpha-lipoic acid 300 to 600 mg/day plus methylcobalamin 500 to 1,000 mg/day IV to prevent the Methylcobalamin monotherapy appears to be superior for improving nerve conduction. (Xu 2013) Also a combination therapy with prostaglandin E1 (10 or 20 µg i.v.), methylcobalamin (500 to 1,500 µg i.v./intramuscularly). [IM]) plus lipoic acid (300 or 600 mg/day IV) significantly improved nerve conduction velocity compared to combination therapy without lipoic acid in a 2015 meta-analysis of 18 randomized clinical trials (N = 1,410) in patients with diabetic peripheral neuropathy. (Jiang 2015)

Limited information suggests that methylcobalamin may play a role in immune modulation and cancer. (Wheatley 2007)

Methylcobalamin has been used in clinical studies to reduce serum homocysteine ​​levels. (Guttuso 2009, Zoccolella 2010)

A Cochrane systematic review and meta-analysis of antioxidants in male subfertility found a double-blind, randomized, parallel study administering vitamin B12 (N=396); However, the lack of usable data prevented inclusion in the meta-analysis. Japanese men with abnormal sperm count or motility received mecobalamin at a dose of either 1,500 or 6,000 mcg/day for 12 weeks. No statistically significant difference was observed in sperm parameters compared to placebo. (Showell 2014)

dosage

The DRI of vitamin B12 is 2.4 µg. The FDA has set the daily reference value (DRV) at 6 mcg. Harvard 2005, Tanaka 1981

One case study reported that methylcobalamin 1,000 mcg i.m. three times a week for 2 weeks, followed by weekly doses, reversed neuropsychiatric symptoms. Sharma 2012

In clinical studies evaluating the effects of methylcobalamin in diabetic neuropathy, doses of 2,500 micrograms of saline in 10 ml were injected intrathecally. Head 2006 and oral methylcobalamin 500 mcg were taken three times daily. Maladkar 2009: In studies of patients with kidney failure-associated neuropathy, 1,500 µg methylcobalamin was administered orally daily for 6 months.Head 2006

Methylcobalamin is at least as bioavailable as cyano- and hydroxycobalamin.Tanaka 1981

The American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update recommends an oral dose of 350 to 500 mg/day (disintegrating tablet, sublingual, liquid) or nasal spray as recommended by the manufacturer for all bariatric weight loss surgery patients (Grade B, Level 2). To treat postoperative deficiency, a dose of 1,000 mg/day until normal limits were achieved and then doses required to maintain normal values ​​was recommended (Grade B, Level 2). (Tabesh 2019)

Pregnancy/breastfeeding

In pregnant women, the recommended intake of vitamin B12 increases to 2.6 mcg/day to meet the needs of the developing fetus. Methylcobalamin supplementation may improve the nutritional status of pregnant women, but data from clinical trials are lacking. Pepper 2011 No reports were found linking high doses of vitamin B12 to maternal or fetal complications. Drugs in Pregnancy 2011

Interactions

Information on interactions caused by methylcobalamin supplementation is not available. Certain drugs are thought to decrease the absorption of vitamin B12, including alcohol, aminosalicylic acid, chloramphenicol, colchicine, metformin, neomycin, and proton pump inhibitors. Facts and comparisons 2011, Ito 2010, Martindale 2011, Saidi 1961

Most antibiotics, methotrexate or pyrimethamine invalidate diagnostic blood tests for folic acid and vitamin B12. Facts and comparisons 2011

Side effects

Vitamin B12 is well tolerated in the dosages contained in foods or dietary supplements. (Bistrian 2010) Gastrointestinal effects of methylcobalamin may include anorexia, nausea, vomiting, and diarrhea. Headache has been reported. (Facts & Compares 2011) High doses of vitamin B12 (more than 5 to 10 mg/week) or long periods of use have been associated with worsening acne, particularly in women. (Zamil 2020)

toxicology

Specific toxicological studies are lacking. Vitamin B12 (as cyanocobalamin or hydroxocobalamin) has long been used safely, even in high doses (cyanocobalamin 1 mg IM at weekly intervals for 1 month, followed by monthly injections for 6 months). At usual dosages, the cobalt and cyanide content is not considered toxicologically relevant. Bistrian 2010, European Commission 2012

Hydroxocobalamin is used in 5 g doses to treat cyanide poisoning.

A study conducted on rats in the 1950s suggested that vitamin B12 may have a tumor-promoting effect, while another study suggested reduced survival rates in rats with Walker's carcinosarcoma treated with methyl- and cyanocobalamin. European Commission 2012

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been evaluated for safety or effectiveness by the FDA and is not subject to the quality and safety information collection standards that apply to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not confirm that this product is safe, effective, or approved to treat any patient or medical condition. This is just a brief summary of general information about this product. It does NOT contain all information about the possible uses, instructions, warnings, precautions, interactions, side effects or risks that may apply to this product. This information does not constitute specific medical advice and does not replace the information you receive from your healthcare provider. You should speak to your doctor to get complete information about the risks and benefits of using this product.

This product may interact negatively with certain health and medical conditions, other prescription and over-the-counter medications, foods or other dietary supplements. This product may be unsafe if used before surgery or other medical procedures. It is important to fully inform your doctor about the herbs, vitamins, minerals, or other supplements you are taking before any surgery or medical procedure. With the exception of certain products generally considered safe in normal amounts, including the use of folic acid and prenatal vitamins during pregnancy, this product has not been adequately studied to determine whether it is safe for use during pregnancy, breastfeeding, or in those younger than 2 years of age.

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