High doses of vitamins can treat genetic diseases - study
Source: NUTRA ingredients
- 08/04/2002 - 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.
Source: NUTRA ingredients
- 08/04/2002 - 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.
“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.
