Methylcobalamin is a human active B-12, which is found in nature and has the potential to raise our B-12 levels like nothing else. We have found that besides taking B-12 shots, these B-12 patches are the most effective B-12 on the market for helping maintain healthy B-12 levels.
The better choice: Methylcobalamin
The proper form of vitamin B-12 to supplement is called methylcobalamin. This is the form that exists in nature, and it is pre-methylated, meaning it's ready for your biochemistry to put to immediate use. Methylcobalamin has several key advantages over cyanocobalamin:
* Increased absorption
* Better retention in tissues
* Contains no toxic cyanide
* Supports production of SAMe
LATEST RESEARCH - Methylcobalamin
What is the difference between Cyanocobalamin and Methylcobalamin? Methylcobalamin is the active form of vitamin B-12 that is better absorbed than many of the other forms like cyanocobalamin. Actually, Vitamin B12 comes in several kinds including hydroxy-, cyano-, and adenosyl-, but only the methyl form is used in the central nervous system.
Here are some of the many uses and benefits of Methylcobalin The methyl form of B-12 especially protects nerve tissue and brain cells, and promotes healthy sleep.
Methylcobalamin is important because it is delivered more efficiently to nerve tissues than regular B-12. Because of this, Methylcobalamin should be considered in the treatment of all neurological diseases.
Based on its mechanism of action, it can be effective in slowing the progression of hard to treat neurological diseases like ALS, Multiple Sclerosis and Parkinson's Disease. Published studies show that high doses can help regenerate neurons and the myelin sheath that protects axons and peripheral nerves. Theraputic doses of Methylcobalamin have also been known to prevent and reverse numbness from nerve damage.
Among the conditions which have responded favorably to Methylcobalamin are, ALS (Lou Gehrig's Disease,) Alzheimer's disease, Bell's Palsy, Parkinson's disease, Multiple Sclerosis, Brain Aging, Insomnia, Immune dysfunction, Chronic Fatigue Syndrome and Fibromyalgia, Schizophrenia, Diabetes, Impotence and Herpes Zoster (Shingles.)
In one study of Alzheimer's patients given Methylcobalamin, the subjects improved their memory, emotions, and ability to communicate. In Alzheimer's or suspected Mercury amalgam related diseases (e.g. MS,) a hidden Vitamin B-12 deficiency has been found, even though the usual blood tests are normal. In one study of patients with chronic, progressive Multiple Sclerosis, 60 mg of Methylcobalamin resulted in clinical improvement in visual and auditory function, but not motor disability.
Methylcobalamin may help prevent Parkinson's disease and slow the progression in those who are already afflicted. Parkinson's is caused by a destruction of brain cells that produce dopamine. Dopamine is produced from the amino acid, L-Dopa. Anyone taking any form of L-Dopa should also take from 5 to 20 mg of Methylcobalamin to enjoy the benefits of L-Dopa for much longer. For best results, it should be taken with Alpha Lipoic Acid. In a sleep study it was shown that Methylcobalamin reduced the amount of time the subjects slept, but the sleep quality was better and subjects awakened refreshed with better alertness and concentration.
Methylcobalamin at 6mg per day for 16 weeks also improved sperm count by 37.5 percent.
In other studies it was found that Methylcobalamin enhances and modulates lymphocytes (white blood cells) by increasing T-Cell (and especially T-helper cells) activity.
In mice, several different kinds of cancerous tumors were suppressed by administration of Methylcobalamin for seven days. These included liver, lung and other tumors.
In a study of Amyotrophic Lateral Sclerosis (ALS) patients, all given high dose (25 mg per day) Methylcobalamin showed increases in muscle strength. Methylcobalamin also slows the progression to AIDS in HIV + patients and helps prevent neurological problems. Methylcobalamin also balances the sympathetic/parasympathetic nervous system (calming when overexcited and stimulating when too calm).
A therapeutic dose for conditions requiring Methylcobalamin would be a minimum of 1500 mcg and a maximum of 6000 mcg per day. No significant therapeutic advantage appears to occur from dosages exceeding this maximum dose; however, it is likely that beneficial physiological effects occur at dosages as low as 100 mcg per day, especially if this dose is given repetitively over time. Methylcobalamin is usually administered in divided doses three times daily. For every day prevention take 1 mg daily under the tongue.
Dr. Edward F. Group III
Cyanocobalamin Versus Methylcobalamin
QUESTION: What is the difference between what you call the "active form" of B12 and the standard health food store/ pharmacy brand. Aren't they both "active?"
ANSWER: Cyanocobalamin is the most commonly supplemented form of vitamin B12, but you might be surprised to discover that this form of vitamin B12 does not actually occur in plants or animal tissues. In other words, outside of the chemically synthesized cyanocobalamin that you encounter as B12 in most vitamin supplements, you would be extremely hard pressed to find this compound in nature (in fact you would not be able to find it). As the name implies, cyanocobalamin contains a cyanide molecule. Most people are familiar with cyanide as a poisonous substance. Although the amount of cyanide in a normal B12 supplement is small and from a toxicology point, viewed as insignificant, your body will still need to remove and eliminate this compound. This removal is accomplished through your detoxification systems with substances like glutathione being very important for the elimination of the cyanide.
Compared with cyanocobalamin, it appears that methylcobalamin is better absorbed and retained in higher amounts within your tissues. In simple terms, they are used much more effectively. In general, methylcobalamin is used primarily in your liver, brain and nervous system.
Methylcobalamin is the specific form of B12 needed for nervous system health. Because of this it should be the first form of this vitamin thought of when interested in attempting to optimize the health of the nervous system with vitamin supplementation. Indications of a potential deficiency of B12 in the nervous system might include numbness, tingling, loss of feeling sensation, burning sensations, muscle cramps, nerve pain and slowness of reflexes.
Because of methylcobalamin's importance in nervous system health, it is also an important nutrient for vision. In fact, continued visual work (like work on a computer) often leads to a reduction in something called "visual accommodation". Methylcobalamin can significantly improve visual accommodation, while cyanocobalamin appears to be ineffective.
An elevated level of homocysteine is a metabolic indication of decreased levels of the coenzyme forms of vitamin B12, especially methylcobalamin. Homocysteine has received a tremendous amount of emphasis in the scientific literature because of its associations with heart disease and a variety of other specific health conditions. I have even seen advertisements on television promoting folic acid, as a vitamin needed to lower homocysteine. While this is true, and folic acid does lower homocysteine levels, the combination of methylcobalamin and folic acid appears to work much better.
The most well studied use of methylcobalamin has to do with sleep. Although the exact mechanism of action is not yet clear, it is possible that methylcobalamin is needed for the synthesis of melatonin. Available information indicates that methylcobalamin can modulate melatonin secretion, enhance light-sensitivity, and normalize circadian rhythm (your 24-hour clock). Because of this, individuals supplementing this form of B12 often have improved quality of sleep, often will require slightly less sleep, and will not uncommonly report that they feel a bit more refreshed when waking in the morning. Methylcobalamin is particularly effective when your 24-hour clock is not running smoothly. This may be indicated by a need for excessive sleep, changing sleep-wake cycles, or a tendency to have altered sleep wake patterns. As examples, you might require 10-12 hours of sleep, or you might not feel tired until 2-3 am and you might wake at noon, or you might find that you wake a bit later every day and go to be a bit later every night. Under all of these circumstances the combination of methylcobalamin (about 3000 mcg daily) and exposure to bright light in the morning can help reestablish your 24-hour clock.
Because of methylcobalamin's impact on 24-hour clock and the cycles that feed of this, it is also an important vitamin to regulate your 24-hour release of the stress hormone cortisol. This seems to be particularly important for blood types A and AB. Methylcobalamin also seems to result in a better 24-hour maintenance of body temperature. Typically individuals supplementing this coenzyme form of B12 have higher temperatures in the later hours of the daytime. This usually corresponds with improved alertness at the same time of the day. While this can be of importance to all blood types, low body temperatures seems to be an area of greater challenge for A's and B's.
Vitamin B12: All Cobalamins are not Equal
"Vitamin B12: All Cobalamins are not Equal
Look at your multiple vitamin or B complex bottle. You're probably taking cyanocobalamin, the stable and less expensive form of vitamin B12. Because it is stable, it has a longer shelf life. However, the active form of B12 is methylcobalamin and the two are NOT equal in effectiveness. If you have symptoms of GI disorders, lethargy, confusion, slow thought processes, heart rate variability, atherosclerosis, sleep disorders, or immune dysfunction, you may need the methyl as well as the cobalamin component.
The two vitamin B12 coenzymes known to be metabolically active in humans are methylcobalamin and adenosylcobalamin. Vitamin B12 is usually absorbed from the gut from the fermentation of intrinsic factor by intestinal flora. However, production can be disturbed by nutritional deficiencies, intrinsic factor deficiency, bacterial overgrowth, malabsorption, alcohol, and antibiotics. Nitrous oxide anesthesia in surgery and nitric acid from normal metabolism and inflammation also reduce our vitamin B12 levels.
Cobalamins are destroyed by heavy metals and strong oxidizing or reducing agents. (take at different times than vit c). Vitamin B12 deficiency generally increases with age and is common in the elderly.(2)
Both vitamin B12 and folic acid are required for the synthesis of thymidylate, a component of DNA. Lack of adequate DNA synthesis causes many red blood cell precursors (hematopoietic cells) to die in the bone marrow. The development of epithelial cells is also disturbed by thymidylate deficiency. Gut changes due to vitamin B12 deficiency are often related to constipation whereas a folic acid deficiency is generally related to diarrhea. In the brain, the arrest of cell replication due to vitamin B12 deficiency disrupts myelin synthesis, resulting in neural damage in the brain, spinal cord and/or peripheral nerves. Vitamin B12 deficiency can include the following neurological symptoms: numbness and tingling in the hands and feet, unsteadiness, poor muscular coordination, moodiness, mental slowness, poor memory, confusion, agitation, and/or depression.
Vitamin B12 is involved in fat and carbohydrate metabolism. It is required in the synthesis of the amino acid methionine, which is involved in choline and betaine utilization. B12 assists in maintaining sulfhydryl (SH) groups in their reduced form for enzyme activity. Vitamin B12 deficiency is associated with a decrease of reduced glutathione, needed for cell defense against pathogens (viruses, bacteria, fungi) and toxins.
Methylcobalamin is a co-factor of methionine synthase, an enzyme that transfers methyl groups to homocysteine to regenerate methionine. Elevated homocysteine levels are a risk factor for coronary artery disease. (11) Methionine can be transformed to S-adenoxylmethionine (SAM) that is involved in a variety of methylation reactions in the body, one of which is alleviating depression.(13)
Methylcobalamin also plays a role in cell-mediated and humoral immune function in rats. In vitamin B12 deficient rats, serum C3, IgM and Ig G factors were found to be lower. There was also an elevation of the ratio of CD4+ CD8- to DC4- CD8+, which reduces the ability to fight off pathogens.(12)
Cyanocobalamin is not biologically active until converted to methylcobalamin, which also means releasing its cyanide. Cyanide can be toxic because it binds the iron (F3+) portion of cytochrome oxidases, preventing its reduction. This binding blocks electron transport and interrupts cellular respiration. Symptoms of sublethal cyanide toxicity include hypotension, tachypnea, and tachycardia.(4)
Cobalamin can bind with cyanide and is therefore effective in reducing cyanide toxicity. However cyanocobalamin is not effective in removing cyanide because the cobalamin is already bound. (3) Since nitroprusside can induce cyanide toxicity, other cobalamins such as hydroxocobalamin should be used to bind with cyanide. Nitroprusside therapies should be minimized in critically ill patients and those with liver or kidney dysfunction.
Large amounts of cyanocobalamin can exacerbate preexisting cyanide toxicity that can result from smoking tobacco, sodium nitroprusside therapy, and phagocytosis. Steve Roach, M.D. writes that "it seems wise to avoid a potentially harmful form of a drug when the more physiologic variety is available and is excreted at a more desirable rate.(7)
Foods fortified with vitamin B12 (as cyanocobalamin) may be a potential problem if cooked. The highest mutation activity in cooked (pyrolysate) vitamins was found in cyanocobalamin (3220 revertants at .025 mumole of cyanocobalamin).(5)
In a comparison of cobalamins against cancer, adenoxylcobalamin was effective against fast-growing malignant cells. Methylcobalamin was effective at elevated concentrations and cyanocobalamin had no effect in slowing the growth of any of the tumor cell lines studied.(6) In studies that show that vitamin B12 has no effect on cancer growth, we need to look closer at whether cyanocobalamin was used instead of the natural coenzyme forms (adenoxylcobalamin and methylcobalamin).
Methylcobalamin enhances synaptic transmission in learning and memory. Ikeuchi and associates studied the effects of methyl-B12 on the electrical activity in hippocampal neurons and found that methyl-B12 increased post-synaptic field potential which lasted more than an hour and increased the electrical currents elicited by N-methyl-D-aspartate (NMDA). Cyanocobalamin had no effect.(13)
Methylcobalamin plays a role in modulating human circadian rhythms. It accelerates re-entrainment of the activity rhythm to the environmental light-dark cycle. The suprachiasmatic nucleus (SCN) is involved in relaying photic information to the pineal gland. Methylcobalamin enhanced the field potential in the SCN that lasted an hour. In contrast, cyanocobalamin showed no effect.(16)
Methylcobalamin is also required in donating a methyl group for the synthesis of melatonin. Methylcobalamin supplementation can assist in modulating melatonin secretion, enhancing light-sensitivity, normalizing circadian rhythms and improving sleep-wake cycles. (17)
Methylcobalamin also helps improve heart rate variability, suggesting that it is involved in balancing sympathetic and parasympathetic nervous system function,(18) perhaps through its involvement with light entrainment and melatonin synthesis. Since circadian rhythm and melatonin synthesis are key factors in health maintenance, the use of cyanocobalamin rather than methylcobalamin is undermining our health as individuals as well as a nation.
Another study found a correlation between serum vitamin B12 in women and their breast milk. When a group of lactating women were injected with cyanocobalamin, there was also an increase of cyanocobalamin in their breast milk.
As early as 1970, Dr. A.G. Freeman protested against the use of cyanocobalamin in The Lancet. He again wrote a letter in 1978, entitled "Why Has Cyanocobalamin Not Been Withdrawn?" to The Lancet and to the British Committee on Safety of Drugs. Dr. Freeman voiced the concern that even if hydroxocobalamin is prescribed, cyanocobalamin is administered in its place. They wrote that "because doctors are still confused about the differences between various forms of vitamin B12 commercially available and about their possible adverse effects, manufacturers should withdraw cyanocobalamin in favor of hydroxocobalamin for therapeutic use." (8)
A letter from Dr. Terry was published in the October, 1978 issue of The Lancet. He wrote that "the lead for improved prescribing must come form compilers of formularies that are highly regarded. In this respect it is disappointing to find that the W.H.O. expert committee on the selection of essentiald rugs lists only cyanocobalamin, placing an incalculable number of patients with optic neuropathy in pernicious anemia or tobacco and tropical amblyopia at risk." (9)
In the November 1978 issue, the Lancet published a letter by J.C.Linnell and associates entitled "Therapeutic Misuse of Cyanocobalamin." The authors state that cyanocobalamin itself has no known biochemical function. Only trace amounts of cyanocobalmin are normally detectable in the human body, while significant amounts occur in patients with optic neuropathies, inborn errors of cobalamin metabolism and pernicious anemia. Cyanocobalamin must first undergo conversion to the physiological forms of cobalamin before being effective against pernicious anemia. However hydroxocobalamin (a precursor to methyl and andenoxylcobalamin) "has the additional advantage of therapeutic efficacy in certain neuropathies and some cases of inborn errors of cobalamin metabolism." The authors further write that "it is lamentable that an extensive demand for cyanocobalamin as a therapeutic agent should persist. There seems to be no place for the continued therapeutic use of cyanocobalamin." (10)
Vitamin B12 is found in algae, peas, clover, alfalfa, mustard, egg yolk, chedder cheese, sardines, herring, anchovies, calve's liver, haddock, salmon, and cow's milk. Plants containing S-methylmethionine include cabbage, kohlrabi, turnip, tomatoes, celery, leeks, garlic, beets, raspberries and strawberries (14). Cyanocobalamin is in haddock and cassava root. Elevated amounts of cyanocobalamin have been found in smokers and cases of amyotrophic lateral sclerosis and optic atrophy.
Clinical doses of methylcobalamin are 1500-6000 mcg per day and can be administered orally, intramuscularly or intravenously with positive clinical results. Methylcobalamin is well tolerated and has no known toxicity. B complex (riboflavin, folic acid, pyridoxine, and choline), and zinc assist methylcobalamin effectiveness. It is important that physicians giving injections check the source of their vitamin B12. Not only can it be cyano rather than methylcobalamin, but the shot gun approach of giving liver extract can include allergenics. One report states that 10-30% of pharmaceutical preparations may be noncobalamin analogues, that are either inactive or cause allergic reactions. (1)
In conclusion, methylcobalamin can be effective in cases of neuropathy, depression, cancer, optic atrophy, heart rate variability, homocysteinemia, and sleep disturbances. However, all cobalamin analogues are not equal and taking cyanocobalamin with already elevated levels of cyanide can actually be harmful. It has been thirty years since Dr. Freeman first published a letter in The Lancet about the risks of using cyanocobalamin. How much longer can we afford to allow ignorance and profit motives to undermine our nation's health?
(1) Herbert, Victor and Neville Colman. "Folic Acid and Vitamin B12" in Shils, Maurice and Vernon R. Young, "Modern Nutrition in Health and Disease." Lea & Febinger, Philadelphia, PA, 1988, pg. 388-416.
(2) Watt, D.T. "Vitamin B12 replacement therapy: how much is enough?" Wisconsin Medical Journal, 1994, 93(5): 203- 5.
(3) Zerbe, N.F. et al. "Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity." Critical Care Medicine, 1993, 21(3): 465-7.
(4) Williams, H.L. et al. "Studies of cobalamin vehicle for the renal excretion of cyanide anion." Journal of Laboratoyr and Clinical Medicine, 1990, 116(1): 37-44.
(5) Demura, R. et al. "Mutagenic activity of pyrolysate of cyanocobalamin and some other soluble vitamins in the model system with the Salmonella/mammalian microsomes." Mutation Research, 1990, 244(1): 37-42.
(6) Tsao, C.S. et al. "Cytotoxic activity of cobalamin in cultured malignant and nonmalignant cells." Pathobiology, 1990, 58(5): 292-6.
(7) Sawyer, D.R. "Cyanocobalmin and cyanide toxicity (letter)." American Family Physician, 1982, 26(1): 48.50,55.
(8) Freeman, A.G. et al. "Why has cyanocobalamin not been withdrawn?" The Lancet, April 8, 1978; pg. 777-778.
(9) Terry, S.I. et al. "Survival of Cyanocobalmin." The Lancet, October 14, 1978, pg. 848.
(10) Linnell, J.C. et al. "Therapeutic Misuse of Cyanocobalamin". Lancet, November 11, 1978; pg 1053-1054.
(11) Brown, C.A. et al. "A Common Polymorphism in Methionine Synthase Reductase Increases Risk of Premature Coronary Artery Disease." J Cardiovasc Risk 2000, 7(3): 197-200.
(12) Funada, U. et al. "Changes in CD4+ CD8-/CD4- CD8+ ratio and humoral immune functions in vitamin B12-deficient rats." Int J Vitam Nutr Res, 2000, 70(4): 167-71.
(13) Ikeuchi, Youji et al. "Methylcobalamin induces a long-lasting enhancement of the postsynaptic field potential in hippocampal slices of the guinea pig." Neuroscience Leters, 1995, 192: 113-116.
(14) Kovatscheva, E.G. et al. "S-methylmethionine content in plant and animal tissues and stability during storage." Nahrung, 1977, 21(6): 465-72.
(15) Schneider, Z. "Comprehensive B12." Walter de Gruyter, New York, New York, 1987.
(16) Nishikawa, Yukiko et al. "Methylcobalamin induces a long-lasting enhancement of the field potential in rat suprachiasmatic nucleus slices." Neuroscience Letters, 1996: 220: 199-202.
(17) Mayer, G. et al. "Effects of vitamin B12 on performance and circadian rhythm in normal subjects." Neuropsychopharmacology, 1996; 15: 456-464.
(18) Yoshioka, K. et al. "Effect of methylcobalamin on diabetic autonomic neuropathy as assessed by power spectral analysis of heart rate variations." Horm Metab Res, 1995, 27: 43-44"
The following supplements contain the Methylated form of B-12 Methylcobalamin:
intraMAX® from Life Enthusiast Co-op
Sublingual B-12 (Methylcobalmin)
Tangy Tangerine (Vitamins & colloidal minerals) buy from Youngevity Online
SUBLINGUAL B12 VITAMIN from Bio-Alternatives
INGREDIENTS: Vitamin B12 (Methylcobalamin) in Pure Water
Serving Size - 1/2 dropper (1000 mcg)
Servings per Container - 60
SUGGESTED USE: As a Dietary Supplement 1/2 dropper once or twice daily.
More choices coming soon...