METHYLCOBALAMIN
and the New Story of Vitamin B12
The 50th anniversary of the discovery of vitamin B12 came
and went and nobody noticed. There were no conferences to mark the occasion, no
fanfares, no speeches, not a mention in the press, not even in the nutritional
media. "Vitamin B12 isn't sexy" was the way a friend, a sports
nutrition consultant, put it. "Just for old people to keep them from
getting anemic." Oh, yeah? Welcome to the new story of vitamin B12.
There's a buzz over B12 these days for two reasons, one scientific and the
other economic. First, the science: Over the last decade or so, researchers
have strongly implicated the toxic amino acid homocysteine in a variety of
disease states. Homocysteine tends to accumulate in the body whenever B12 gets
deficient, and this accumulation has been linked with increased risk of
Alzheimer's disease [1,2], cardiovascular disease [3], chronic fatigue
syndrome/fibromyalgia [4] and multiple sclerosis [5] among other conditions.
Folic acid deficiency can also lead to increased homocysteine levels -
that's because folate and B12, in their active "coenzyme" forms, are
both necessary cofactors for the enzymatic conversion of homocysteine to
methionine. Until recently it's been thought that the availability of folate
was the most important determinant of the body's ability to remethylate
homocysteine. New research has revealed that vitamin B12 is more important for
homocysteine disposal than once believed [3,6,7]. In particular, a study
conducted among dialysis patients with kidney failure showed that a monthly
shot of B12 plus conventional oral folate was more effective than high-dose
folate without B12 in lowering elevated homocysteine [6].
The coenzyme form of vitamin B12 is known as METHYLCOBALAMIN or METHYL B12.
It's the only form of vitamin B12 which can directly participate in
homocysteine metabolism. In addition, converting homocysteine to methionine via
methyl B12 generates an increased supply of SAMe (S-adenosyl methionine), the
body's most important methyl donor. Indeed, some of the benefits of methyl B12,
such as protection from neurotoxicity, appear to derive from increased
production of SAMe [8,9]. Methyl B12 has also been reported to be neurotrophic,
or growth-promoting, for nerve cells [10,11], a property which may help
regenerate central and peripheral nervous tissues damaged in disorders such as
amyotrophic lateral sclerosis [12] and diabetic peripheral neuropathy [13].
All of this scientific news is hot stuff, but it's still only half the
story. The other half is that starting around 1998, methylcobalamin first
became widely available in this country at an affordable price, thus offering
new options for treating B12 deficiencies and lowering elevated homocysteine.
Before then, methyl B12 had been enormously expensive and widely available only
in Japan, where it still remains a prescription medication. Today any
health-conscious American consumer can easily access the most powerful known
form of vitamin B12.
When most of us think of vitamin B12, the molecule we really have in mind
is cyanocobalamin or cyano B12. As its name suggests, cyano B12 has a cyanide
group (CN) attached, whereas methyl B12 carries a methyl group (CH3) instead.
Very little of the body's natural B12 is in the cyano form under normal
circumstances; exceptions are in cases of cyanide poisoning or chronic smoking,
both of which can raise cyanocobalamin levels. The fact that most of our
vitamin pills contain cyano rather than methyl B12 is largely an accident of
history, the result of using charcoal to filter extracts during the isolation
of B12. Unknown to the early researchers who first isolated B12, the traces of
cyanide present in such charcoal rapidly convert all natural forms of B12,
including methyl B12, into the more stable cyano form. As a result, the
discovery of the B12 coenzymes and their metabolic role was delayed for years.
Whenever we swallow a conventional vitamin pill, any cyano B12 present gets
carried along and absorbed by an intricate "bucket brigade" of
B12-binding proteins. Operating in the stomach and small intestine, this
transport system provides a very efficient mechanism for absorbing a few
micrograms of B12, yet is quickly swamped by anything larger. As a result, only
about 1% of a large oral dose of any form of B12 usually makes it into the
bloodstream. Fortunately, we can bypass intestinal absorption entirely by
giving B12 by injection or sublingually. In particular, sublingual
administration is a simple and effective way of substantially raising blood
levels by absorbing B12 through the oral mucosa. It's also unquestionably the
most convenient way to take B12, especially for people taking supplements on a
daily basis.
So let's say we've taken a sublingual tablet and a significant amount of
B12 shows up in the bloodstream. End of story? Not if it's cyano B12. Most of
the B12 naturally circulating in the blood is in the methyl form. Before cyano
B12 can join this metabolic pool and be properly utilized by the body, it must
be stripped of its cyano group and "reduced" (i.e., made to gain
electrons) in a time-consuming, multi-step process [1,4]. The result of all
this processing is a B12 molecule with its cobalt ion reduced from the +3 to
the +1 oxidation state, ready to take on a methyl group and be distributed
throughout the body as methyl B12.
It should be obvious there are certain advantages inherent in taking methyl
B12 as a supplement, versus "ordinary" B12. For one thing, methyl B12
needn't engage the body's resources to convert it into coenzyme form - it's
already there. Even more important is the fact methylcobalamin is the most
highly reduced form of vitamin B12 possible; this makes methyl B12 a very
potent reducing agent (antioxidant) indeed. In a body undergoing oxidative
stress, for example, from a disease process or from a diet deficient in
antioxidants, it's possible methyl B12 production can become impaired. A
similar derangement in the cellular synthesis of adenosyl B12 (another reduced
coenzyme form of B12, into which methyl B12 can be converted) is already known
to occur in association with vitamin E deficiency [15]. So it makes sense to
consume B12 in a form in which it's already metabolically active and maximally
reduced, and thereby put less of a strain on our bodies' antioxidative
capacity.
How much methyl B12 should be taken for optimal health? In some studies on
animals and humans, big doses (equivalent to 25-40 mg per day for an adult
human) were found to halt or improve neural degeneration [10,12]. The problem
is, nobody knows the long-term effects of such huge doses. A more prudent
approach would be to take about a tenth as much - say, 3 mg per day - as a
maintenance dose, with the dose increased as needed in cases of increased
stress, oxidative or otherwise. (1 mg=1000 mcg)
So here's a belated "Happy 50th Birthday" to B12. With all the
health and pro-longevity benefits of methyl B12 now becoming evident -
including warding off such age-related diseases as Alzheimer's [1,2],
atherosclerosis [3], rheumatoid arthritis [16] and possibly even cancer
[17,18], it seems the old vitamin has some new life in it. May it and we
continue in partnership for many birthdays yet to come.
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REFERENCES
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[14] Pezacka E, Green R, Jacobsen DW. Glutathionylcobalamin
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[15] Turley CP, Brewster MA. Alpha-tocopherol protects
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stressed human cells. J Nutr 1993;123(7):1305-12.
[16] Yamashiki M, Nishimura A, Kosaka Y. Effects of
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Ed Sharpe, 1999
Diabetic
Neuropathy.org & Diabetic-Neuropathy.org
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