may be useful treatment for many genetic diseases, or just good
insurance to tune up body's metabolism
Sanders, Media Relations
Linus Pauling's claim that megadoses of vitamin C can
prevent colds remains unproven, yet high doses of some vitamins
could play a big role in the treatment of disease and perhaps
slow the effects of aging, according to a University of California,
biochemist Bruce Ames on how megavitamins may tune up
a review article in the April issue of The American Journal
of Clinical Nutrition, UC Berkeley's Bruce N. Ames lists
more than 50 genetic diseases successfully treated with high
doses of vitamins, most of them rare inborn metabolic diseases
due to defective enzymes.
found a common thread in the effectiveness of these megavitamin
therapies that suggests there may be many more diseases treatable
with high-dose vitamins, in particular the eight B vitamins
like niacin, thiamine and pyridoxine. And because aging involves
similar biochemical deficiencies, megavitamins may help perk
up an increasingly older population.
that the big impact is going to be in aging," Ames said,
though younger people, too, might benefit from supplementary
B vitamins to "tune up" their metabolism. Ames is
a professor of molecular and cell biology at UC Berkeley and
a researcher at Children's Hospital Oakland Research Institute
vitamin therapy is the use of vitamins in amounts considerably
greater than the recommended daily allowance, or RDA. Ames noted
that many B vitamins are sold over the counter in high dosages
and are generally considered safe at such levels, although side
effects have been reported after taking very high levels of
some of them, such as pyridoxine and niacin.
In his paper,
co-authored with recent UC Berkeley graduate Ilan Elson-Schwab
and former CHORI technician Eli A. Silver, Ames argues that
the key to the effectiveness of high-dose vitamin therapy lies
in the role vitamins play in the body. Vitamins are converted
to coenzymes, which team up with enzymes to perform some essential
found in a computer sweep of the literature, about 50 diseases
result from a genetic mutation that reduces the ability of an
enzyme to bind to its coenzyme, thereby reducing the rate at
which the enzyme catalyzes a molecular reaction. Saturating
the body with high doses of the appropriate vitamin increases
coenzyme levels to overcome the binding defect and boost the
reaction rate towards normal.
who turn beet red after drinking alcohol can chalk it
up to a genetic variation, or polymorphism, that prevents
them from quickly metabolizing alcohol. This probably
is responsible for the low incidence of alcoholism in
Asian countries, but it also contributes to higher rates
of oral, throat and stomach cancers. Vitamin B-3, or niacin,
might help alleviate the problem, Ames said. More.
packed with protein and fiber, beans have always been
problematic. In the 6th century BC, the Greek geometer
Pythagoras even founded a cult that prohibited the eating
of fava beans, the main bean in the Mediterranean at the
thinks Pythagoras based his proscription on a common medical
problem triggered by eating fava beans, and suggests that
some forms of the problem are caused by defective binding
between an enzyme and its niacin-based coenzyme. More.
50 diseases are just the tip of the iceberg," Ames said.
"Individual doctors have noticed this, but nobody put it
all together. Now, doctors are going to try high-dose vitamin
therapy the minute they know a coenzyme is involved in a disease
or there is a problem with the substrate. It makes sense, since
many of the vitamins are generally recognized as safe in large
doses. I think this kind of thing will turn up all over once
people start looking."
In the paper,
Ames and Elson-Schwab estimate that up to one-third of all mutations
in a gene may affect binding to a vitamin-derived coenzyme,
which means that high-dose vitamin therapy might reverse the
effects of these mutations.
has far broader implications than just the treatment of genetic
disease. The human genome is rife with genetic variation that
probably affects enzyme-coenzyme interactions, and thus vitamin
requirements. High-dose vitamins might tweak enzyme functioning
enough to improve the health of many segments of society, Ames
said. Eliminating vitamin and mineral deficiencies will restore
what he calls "metabolic harmony."
and iron deficiency, vitamin C, B-12 and B-6 deficiencies are
very common," he said. "Yet, a multivitamin pill costs
only a penny to make - you can buy a year's supply for ten dollars.
Everybody in the world should take one as insurance and try
to eat a good diet."
the body with an excess of some enzyme cofactors may perk up
the aging body, too, since aging is accompanied by oxidative
damage to many proteins and enzymes. Last month, Ames and his
colleagues reported in Proceedings of the National Academy of
Sciences that aging rats responded to treatment with an antioxidant,
alpha-lipoic acid, and another substance, acetyl-L-carnitine,
that binds to an important enzyme in the energy-producing organs
of each cell, the mitochondria. Treated mice were more energetic
and had better memory.
acetyl-L-carnitine, he said, compensates for the defective binding
of the enzyme, carnitine acetyltransferase. Together, these
two play a key role in burning fuel in mitochondria.
suspected that enzyme/coenzyme binding might be at the root
of many diseases while teaching an undergraduate laboratory
course in biochemistry 30 years ago. As students isolated mutant
microbes and characterized the defective genes, they found that
many coded for enzymes with a problem binding to a cofactor.
In Elson-Schwab, Ames found an energetic undergraduate able
to search the literature for diseases that fit this scenario
and to locate biochemical data indicating a cause.
Of the 50
diseases he tracked down, 11 respond to pyridoxine, or vitamin
B-6. These include enzyme diseases that lead to blindness, mental
retardation, kidney failure and developmental problems. In all
of these, scientists have pinned the disease to a problem in
how an enzyme binds to a cofactor derived from vitamin B-6.
point out that, of 3,870 known enzymes, 22 percent use cofactors
and 112 of those utilize B-6. There may be diseases associated
with every one of these enzymes, each treatable, to some degree,
by megadoses of B-6 or another vitamin or cofactor. Also, due
to genetic variation, some people have enzymes with less coenzyme
binding affinity than normal, and thus are able to benefit from
high doses of particular vitamins.
found 22 other diseases caused by defective binding to a cofactor
derived from a B vitamin, including thiamine (B-1), riboflavin
(B-2), niacin (B-3), cobalamin (B-12) and biotin (B-7).
interesting is, health food stores sell B-100 pills with 50
times the normal requirement for vitamin B-6, which is about
a milligram. It never made much sense to the nutrition community,
and yet the public is buying these pills. Why?
somebody just feels better when they take these high B-vitamins.
All the neurotransmitters in the brain, such as serotonin, use
vitamin B-6. So maybe when you take high levels it raises serotonin
levels in the brain. There is some evidence for that."
said individual doctors have noticed the connection between
coenzyme binding problems and response to high-dose vitamin
therapy, but no one had put all the puzzle pieces together.
Pauling even suggested, with little evidence, that much mental
illness may be due to deficiencies of some micronutrients, and
that brain dysfunction may involve mutations that affect enzyme-cofactor
order to stimulate discussion of their ideas, Ames and Elson-Schwab
have created a Web site - http://www.KmMutants.org - where scientists
and lay people alike can share information about megavitamins
physicians use safe dosages, "there is potentially much
benefit and possibly little harm in trying high-dose nutrient
therapy because of the nominal cost, ease of application and
low level of risk," the authors concluded in their paper.
research was funded by grants from the Ellison Foundation, the
National Foundation for Cancer Research, the Wheeler Fund of
the Dean of Biology at UC Berkeley and the National Institute
of Environmental Heath Sciences Center, funded by the National
Institutes of Health.