Vitamins work for 50 genetic disorders

08/04/02 - More than 50 genetic disorders can be successfully treated with
high doses of vitamins, according to a recent article by a professor at UC
Berkley in the US.

Writing in the April issue of The American Journal of Clinical Nutrition,
Bruce N. Ames said that he had discovered a common thread in the
effectiveness of so-called megavitamin therapies which suggested that
there may be many more diseases treatable with high-dose vitamins, in
particular the eight B vitamins like niacin, thiamine and pyridoxine. He
said that because the ageing process often involved similar genetic
changes to some of the diseases helped by vitamin therapies, the prospect
of the treatment being used to help fight ageing was a distinct one.

"I suspect that the big impact is going to be in ageing, though younger
people, too, might benefit from supplementary B vitamins to 'tune up'
their metabolism," said Ames. Megadose vitamin therapy is the use of
vitamins in amounts at least 10 times greater than the recommended daily
allowance, or RDA. Ames noted that B vitamins are sold over the counter in
dosages up to 100 times the RDA, and are generally considered safe at such
levels.

Ames said that the key to the effectiveness of high-dose vitamin therapy
lay in the role vitamins play in the body. Vitamins are converted to
coenzymes, which team up with enzymes to perform some essential metabolic
function. An analysis of existing data showed that around 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
catalyses 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, Ames said.

Ames gave the example of Asians, who often turn a deep shade of red after
drinking alcohol because of a genetic variation, or polymorphism, that
prevents them from quickly metabolising alcohol. This is probably
responsible for the low incidence of alcoholism in Asian countries, but it
also contributes to higher rates of oral, throat and stomach cancers, he
said. However, vitamin B-6, or niacin, might help alleviate the problem.

"These 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
recognised as safe in large doses. I think this kind of thing will turn up
all over once people start looking."

Ames and his co-researchers estimated that up to one-third of all
mutations in a gene might affect binding to a vitamin-derived coenzyme,
which means that high-dose vitamin therapy might reverse the effects of
these mutations. The theory has far broader implications than just the
treatment of genetic disease, however. 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.' "Zinc 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 treatment could well prove effective in slowing the ageing process as
well, Ames said, as ageing is accompanied by oxidative damage to many
proteins and enzymes. Ames has already carried out research on rats which
showed that they 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. The
extra acetyl-L-carnitine, he said, compensated for the defective binding
of the enzyme, carnitine acetyltransferase. Together, these two play a key
role in burning fuel in mitochondria.

Of the 50 diseases Ames' team studied, 11 responded to pyridoxine, or
vitamin B-6. These included 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. The authors pointed out that, of
3,870 known enzymes, 22 percent use cofactors and 112 of those use 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. The authors 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).

"What's 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? "Maybe 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
Ames. Provided 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.

The 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.

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