Methylcobalamin B12 supplement benefit and side effects, proper dosage, 5mg pills - Cobalamin information
August 2 2018
by Ray Sahelian, M.D.

Methylcobalamin is one of the two coenzyme forms of vitamin B12 (cobalamin). Vitamin B12 plays an important role in red blood cells, prevention and treatment of anemia, methylation reactions, and immune system regulation. Evidence indicates it has some metabolic and therapeutic applications not shared by the other forms of vitamin B12.

Rev Prat. 2013. Vitamin B12 cobalamin. The term "vitamin B12" refers to four cobalamins (Cbl), including methyl-Cbl and adenosyl-Cbl, the two enzyme co-factors of methionine synthase and methylmalonyl-CoA mutase, respectively. Vitamin B12 deficiency produces clinical disorders that include mainly megaloblastic anaemia, peripheral and central neurological manifestations. The clinical significance of low blood B12 concentrations in the absence of manifestations of deficiency is a matter of debate. The biochemical diagnosis of the subclinical and clinical deficiency of vitamin B12 has been enriched by several parameters, including serum methylmalonic acid, homocysteine, and holo-transcobalamine, which have been evaluated over the past two decades.

Methylcobalamin is the active form of vitamin B12 that acts as a cofactor for methionine synthase in the conversion of homocysteine to methionine, thus lowering blood levels of homocysteine. It
acts as a methyl donor and participates in the synthesis of SAM-e (S-adenosylmethionine), a nutrient that has powerful mood elevating properties. Vitamin B12 can be absorbed sublingually, orally, and in a doctor's office it can be given by injection.

Q. Been searching for a B12 Nasal delivery product. Very few and expensive. Any problem using an oral B12 product which has no additives such as flavors or sweeteners? I have found two such B12 sprays: B12MC by DaVinci Labs and Pure Advantage B12 (Amazon).
   A. B12MC by DaVinci Labs and Pure Advantage B12 (Amazon) appear to be fine products. Oral B12 is absorbed just as well and I do not see the need for a nasal delivery method.

Clinical Uses and benefits
Methylcobalamin supplements increase alertness and body temperature.
May slightly help those with diabetic neuropathy. A better nutrient for this condition is lipoic acid.
It has been found to be helpful in Bell's palsy. However, I don't have personal experience to determine whether when given in a doctor's office to actual patients with Bell's palsy it really helps or not.
Methylcobalamin taken orally is effective in the treatment of pernicious anemia, says a Japanese study.
Methylcobalamin may inhibit the ototoxic (hearing damage) side effects of the antibiotic gentamicin.

Brain health
Vitamin B-12 is essential for brain development, neural myelination, and cognitive function. Inadequate vitamin B-12 status during pregnancy and early childhood has been associated with adverse child health outcomes, including impaired cognitive development.

Pain decrease
Neural Plast. 2013. Methylcobalamin: A Potential Vitamin of Pain Killer. Methylcobalamin (MeCbl), the activated form of vitamin B12, has been used to treat some nutritional diseases and other diseases in clinic, such as Alzheimer's disease and rheumatoid arthritis. As an auxiliary agent, it exerts neuronal protection by promoting regeneration of injured nerves and antagonizing glutamate-induced neurotoxicity. Recently several lines of evidence demonstrated that MeCbl may have potential analgesic effects in experimental and clinical studies. For example, MeCbl alleviated pain behaviors in diabetic neuropathy, low back pain and neuralgia. MeCbl improved nerve conduction, promoted the regeneration of injured nerves, and inhibited ectopic spontaneous discharges of injured primary sensory neurons. This review aims to summarize the analgesic effect and mechanisms of MeCbl at the present.

Diabetic neuropathy
Curr Med Res Opin. 2015 . Nutritional management of patients with diabetic peripheral neuropathy with L-methylfolate-methylcobalamin-pyridoxal-5-phosphate: results of a real-world patient experience trial.

Cobalamin and methylcobalamin biochemistry
The B12 or cobalamin coenzymes are complex macrocycles whose reactivity is associated with a unique cobalt-carbon bond. The two biologically active forms are methylcobalamin and AdoCbl and their closely related cobamide forms. Methylcobalamin participates as the intermediate carrier of activated methyl groups. During the catalytic cycle the coenzyme shuttles between methylcobalamin and the highly nucleophilic cob(I)alamin form. Examples of methylcobalamin -dependent enzymes include methionine synthase and Me-H4-MPT: coenzyme M methyl transferase. AdoCbl functions as a source of carbon-based free radicals that are unmasked by homolysis of the coenzyme's cobalt-carbon bond. The free radicals are subsequently used to remove non-acid hydrogen atoms from substrates to facilitate a variety of reactions involving cleavage of carbon-carbon, carbon-oxygen and carbon-nitrogen bonds.

Coenzyme B12 (cobalamin)-dependent enzymes.
Essays Biochem. 1999.
The B12 or cobalamin coenzymes are complex macrocycles whose reactivity is associated with a unique cobalt-carbon bond. The two biologically active forms are methylcobalamin and AdoCbl and their closely related cobamide forms. Methylcobalamin participates as the intermediate carrier of activated methyl groups. During the catalytic cycle the coenzyme shuttles between methylcobalamin and the highly nucleophilic cob(I)alamin form. Examples of methylcobalamin -dependent enzymes include methionine synthase and Me-H4-MPT: coenzyme M methyl transferase.

Dibencozide coenzyme
Dibencozide is an active coenzyme form of vitamin B-12. It is required for processing branched chain amino acids through the Krebs cycle.

Cobalamin information
Vitamin B12, or cobalamin, is one of the most structurally complex small molecules made in Nature. Adenosyltransferase converts cobalamin to coenzyme B(12).
   Four cobalamines (methyl-, hydroxy-, adenosyl- and cyancobalamines) are considered as natural forms of vitamin B12 in human and animal tissues. Methyl- and adenosylcobalamines are the coenzymes of more than 10 enzymes, catalyzing important reactions of lipid, carbohydrate and protein metabolism. The four natural forms of vitamin B12 are interconverted in presence of corresponding enzymatic systems. Content of individual forms of cobalamines and of corresponding coenzymes depends on the function of enzymatic systems involved in their synthesis as well as on the enzymes, which use these derivatives as coenzymes. Spectra of cobalamines in human and animal bodies are dynamic systems, distinctly and specifically responding to various effects.

The biosynthetic route to adenosylcobalamin from its five-carbon precursor, 5-aminolaevulinic acid, can be divided into three sections: (1) the biosynthesis of uroporphyrinogen III from 5-aminolaevulinic acid, which is common to both pathways; (2) the conversion of uroporphyrinogen III into the ring-contracted, deacylated intermediate precorrin 6 or cobalt-precorrin 6, which includes the primary differences between the two pathways; and (3) the transformation of this intermediate to form adenosylcobalamin.

Deficiency due to medication use
Proton pump inhibitors also reduce the absorption of vitamin B12 probably by inhibiting intragastric proteolysis and, thus, its release from food required prior to binding to R-proteins and gastric intrinsic factor.
Metformin, a drug used for diabetes management, could cause deficiency.

Proton-pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and metformin can reduce serum vitamin B-12 concentrations by inhibiting the absorption of the vitamin.

Research study
Oral supplements of vitamin B12 appear to correct vitamin B12 deficiencies as well as B12 injections. However, in order to correct a deficiency, oral doses need to contain more than 200 times the recommended daily allowance (RDA) of vitamin B12. Study author Dr. Lisette C. P. G. M. de Groot of Wageningen University in the Netherlands explained that most people develop vitamin B12 deficiencies as a result of "malabsorption," in which their bodies become unable to extract vitamin B12 from food. The deficiency typically strikes older people, she added, and takes years to develop. In some instances, people who avoid animal products -- such as vegans and followers of a macrobiotic diet -- can also develop a deficiency in vitamin B12 as a result of not eating enough B12-rich foods. A vitamin B12 deficiency is typically treated by monthly, often painful, shots. To investigate whether an oral dose of vitamin B12 works, as well, they tested various daily doses of oral vitamin B12 supplements in 120 people aged 70 and older. They found that daily oral doses of 647 to 1032 micrograms of vitamin B12 appeared to correct the deficiency. The current RDA for vitamin B12 is 3 micrograms per day. Archives of Internal Medicine, May 23, 2005.

Mothers with low levels of vitamin B12 in their blood are at increased risk of having an infant with spina bifida -- a birth defect in which the spinal cord fails to form properly. Based on previous research, pregnancy guidelines recommend that women consume enough folic acid to reduce the risk of spina bifida and related problems. The new findings suggest that these guidelines should also include recommendations about vitamin B12.

The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes.
Annu Rev Biochem. 2003.
Vitamin B12 is a complex organometallic cofactor associated with three subfamilies of enzymes: the adenosylcobalamin-dependent isomerases, the methylcobalamin -dependent methyltransferases, and the dehalogenases. Different chemical aspects of the cofactor are exploited during catalysis by the isomerases and the methyltransferases. Thus, the cobalt-carbon bond ruptures homolytically in the isomerases, whereas it is cleaved heterolytically in the methyltransferases. The reaction mechanism of the dehalogenases, the most recently discovered class of B12 enzymes, is poorly understood. Over the past decade our understanding of the reaction mechanisms of B12 enzymes has been greatly enhanced by the availability of large amounts of enzyme that have afforded detailed structure-function studies, and these recent advances are the subject of this review.

Cobalamin-dependent methyltransferases.
Acc Chem Res. 2001.
Cobalamin cofactors play critical roles in radical-catalyzed rearrangements and in methyl transfers. This Account focuses on the role of methylcobalamin and its structural homologues, the methylcorrinoids, as intermediaries in methyl transfer reactions, and particularly on the reaction catalyzed by cobalamin-dependent methionine synthase. In these methyl transfer reactions, the cobalt(I) form of the cofactor serves as the methyl acceptor. Biological methyl donors to cobalamin include N5-methyltetrahydrofolate, other methylamines, methanol, aromatic methyl ethers, acetate, and dimethyl sulfide. The challenge for chemists is to determine the enzymatic mechanisms for activation of these unreactive methyl donors and to mimic these amazing biological reactions.

Effects of vitamin B12 on performance and circadian rhythm in normal subjects.
Neuropsychopharmacology. 1996.
This preliminary study investigates effects of methyl- and cyanocobalamin on circadian rhythms, well-being, alertness, and concentration in healthy subjects. Six women (mean age 35 years) and 14 men (mean age 37 years) were randomly assigned to treatment for 14 days with 3 mg cyano-(CB12) or methylcobalamin (MB12) after 9 days of pre-treatment observation. Levels in the CB12 group increased rapidly in the first, then slowly in the second treatment week, whereas increase in the MB12 group was linear. Urinary aMT6s excretion was reduced by both forms of vitamin B12 over 24 hours with a significant decrease between 0700-1100 hours, whereas urinary excretion of potassium was significantly increased between 0700-1100 hours. Activity from 2300-0700 hours increased significantly under both forms of vitamin B12. Sleep time was significantly reduced under MB12 intake. In this group the change in the visual analogue scales items "sleep quality," "concentration," and "feeling refreshed" between pretreatment and the first week of treatment showed significant correlations with vitamin B12 plasma levels. Cortisol excretion and temperature were not affected by either medication. We conclude that vitamin B12 exerts a direct influence on melatonin. Only MB12 has a positive psychotropic alerting effect with a distribution of the sleep-wake cycle toward sleep reduction.

I have been in and out of this website periodically for a number of years. The site is very informative and so was the book "Mind Boosters". I am not formally educated in medicine or biochemistry so please remember this when replying to my question. How does B12, in particular methylcobalamin, work to raise body temperature?
   Yes, B12 or methylcobalamin can raise body temperature in a high dose.

Q. I just recently got a home PC and internet access. I now have the time and desire to do extensive research on various topics, one of the highest on the list being health issues. I suffer from depression, which has recently become treatment-resistant. After MANY HOURS of research and reading, I have happened across your website NUMEROUS times, and have not once been disappointed!! Your site is a goldmine, in numerous ways. First, your objective honesty and accuracy. Next, the sheer volume of information. I love technical details!! And most valuable, the availability of certain products that one just can't find anywhere else!! Just before I compiled this email, I found your vitamin B12 supplement, consisting of both Methylcobalamin AND Adenosylcobalamin !! AWESOME!! I LOVE YOU GUYS!! Keep up the great work!!

Q. I've been seeing a lot of hype--on TV about how absorbable sublingual B-12 is because it is not swallowed but absorbed under the tongue. My question is this: Have you studied this way of taking vitamins or have you seen any studies to support the claims made.
   A. Vitamin B12 can be absorbed sublingually, orally, and in a doctor's office it can be given by injection. Most of the supplements of b12 are in such high doses anyway, that even if there were some differences in absorption between the 3 methods, practically speaking it makes little difference.

Q. I recently heard a radio health program where the topic was the B vitamins. It was stated that Cyano Cobalamin replaces the mercury in the brain with Cyanide, that Methyl Cobalamin removes the Magnesium from the brain and the best B12 was Hydroxy Cobalamin. I have been taking 1000 mg of Methyl for tingling fingers but have stopped. Will you please comment?
   A. Many things are said on radio or the internet that don't have any studies to validate the claims. I have not yet come across research that supports this viewpoint. At this time I am comfortable with the use of all types of cobalamin preparations in reasonable amounts.

Q. I'm a bit confused regarding the forms of B12 specifically cyanocobalamin vs. methylcobalamin. Is the latter a coenzyme of the former and are they interchangeable in terms of use. Specifically is the methyl form useful for those suffering from anemia.
   A. We have not seen human studies comparing cyanocobalamin to methylcobalamin, Methylcobalamin is the methylated form of cobalamin and may be more active and useful, but we are not sure of this. At this time, for practical purposes, the two forms may be used interchangeably until studies are published that indicate one form is better than the other. If we had to choose between the two, we probably would pick methycobalamin as the better option although we cannot be 100 percent certain of this. The name vitamin B12 is refers to a group of cobalt-containing compounds known as cobalamins - cyanocobalamin, hydroxocobalamin and the two coenzyme forms of B12, methylcobalamin and 5-deoxyadenosylcobalamin (adenosylcobalamin - AdoB12).

Found this info on your web-site: "Methylcobalamin is one of the two coenzyme forms of vitamin B12 (cyanocobalamin). Vitamin B12 plays an important role in red blood cells, prevention and treatment of anemia, methylation reactions, and immune system regulation. Evidence indicates methylcobalamin has some metabolic and therapeutic applications not shared by the other forms of vitamin B12." My understanding is Cyanocobalamin has a cyanide molecule added to the vitamin, so the Methylcobalamin doesn't contain a cyanide molecule. Is this correct?
   To the best of our understanding, cyano refers to (-CN). Cyanocobalamin is a synthetic form of vitamin B12.
Cyanocobalamin is used to treat pernicious anemia, nutritional vitamin B12 deficiency, malabsorption and other cases of vitamin B12 deficiency.

Is it possible you can help me to get injectable methylcobalamin. I live in Denmark, and here we need a recept from the doctor, but my doctor will not give me. He is very old fashion. But I have done a lot of recearch in long time on M. I think it could help me with the tiredness that I feel. At least I could try! I'm 54 years.
    Sorry, I cannot. See the information page on fatigue and you may find other ways to improve your tiredness. Oral methylcobalamin works well without the need for injections.

Information pages of interest
Lycopene from tomato
Pygeum Africanum extract found in Prostate products
Quercetin flavonoid

Saw Palmetto extract found in prostate products including Prostate Power Rx
Sitosterol or beta sitosterol
erectile dysfunction herbal solution

carnosine antioxidant
carnitine as energy booster
dopamine brain chemical
female libido enhancers
libido enhancers
horny goat weed aphrodisiac is found in an effective sexual enhancing supplement called Passion Rx
kava is used for anxiety
maca is from South America
pregnenolone is a precursor to DHEA
melatonin is a pineal hormone
tribulus terrestris sex enhancer
yohimbe for erection help

I bought MultiVit Rx, but the label does not indicate the type of B12. On the web site, the contents indicate that it is methylcobalamin, which is the specific form I am looking for. Would you please confirm what type of B12 is in MultiVit Rx.
   The MultiVit Rx contains methylcobalamin.

After doing extensive research on Cyanocobalamin versus Methylcobalamin, we have passed the information on to our doctor and he is enthusiastic to prescribe us the Methylcobalamin B12 injections. My husband has a vitamin B12 deficiency. He's been doing the Cyanocobalamin injections for about 2 weeks, and he has some improvement but his hands are still numb. His career is highly dependent on his hands. The roadblock that we have encountered is that we are located in Los Angeles and the only sources that I've found online to provide Methylcobalamin injections are Hopewell Pharmacy in the North East. I've called countless pharmacies in the LA area and they've told me that they only carry the Cyano B12 injectable. Is there a pharmacy in your medical building that stocks the Methylcobalamin injections, that we can perhaps have our doctor call in?
   Not in our office, I personally use high dosages of oral methylcobalamin in those who are deficient, which seems to work for my patients.

buy Methylcobalamin Vitamin B-12 Complex, 5 mg
Source Naturals, Advanced B-12 Complex, 5 mg, 60 Tablets
Methylcobalamin and Adenosylcobalamin

Advanced B-12 Complex combines the two active, coenzymated forms of vitamin B-12 - methylcobalamin and adenosylcobalamin (dibencozide) - with folic acid. Vitamin B-12 is required for normal growth, cell reproduction, myelin and nucleoprotein synthesis, and the formation of red blood cells. Coenzyme supplementation bypasses the body's need to synthesize the active forms of vitamin B-12 from cyanocobalamin.

Buy Methylcobalamin Vitamin B12 complex 5 mg

Supplement Facts
Serving Size: 1 Tablet
  Amount Per Serving %DV
Folate (as folic acid) 400 mcg 100%
Vitamin B-12 (as methylcobalamin and adenosylcobalamin) 5 mg 84,400%

Dietary Supplement

Buy Methylcobalamin Vitamin-B12

Supplement Facts:
Folate (as folic acid)
Vitamin B12 (as methylcobalamin and dibencozide [adenosylcobalamin]

Suggested Use: One methylcobalamin tablet 2 or 3 times a week or as directed by your doctor.

Q. Regarding the vitamin b-12 supplement you recommended (Source Naturals 5mg), the directions state to take 2-3 times a week. What would be the advantage of taking it this way, instead of taking a lesser dose (half tablet) daily? Additionally is there known to be any negative effect to taking high doses of vit B-12, when taken orally?
   A. It is probable that both options, taking a full tablet two or three times a week, or half a tablet daily could provide similar results. It is possible, though, that providing a large amount at one time may improve absorption. I have not seen studies comparing the two approaches. No major side effects are obvious, but as with any dietary supplement it is best to be reasonable in one's intake.

Other products sold online
Garden of Life, MyKind Organics, B-12 Organic Spray, Raspberry, 2 oz (58 ml)
Solgar, Sublingual Methylcobalamin (Vitamin B12), 1000 mcg, 60 Nuggets