Nutritional supplementation and genetics

My thanks today to Tammy Antzler, who supplied me with three references to information on research and progress in personalized nutrition. 

The first reference is a 75-page report from the Department of Health and Human Services on Personalized Health Care (PHC). The report details agencies of the government that are involved in the many different aspects of PHC. There are a few, very brief, references to diet, environnment, and genetics. These are generally genome studies--populations, not individuals.

The second reference is a recent article in Science Daily, titled Good news in our DNA: Defects you can fix with vitamins and minerals. The article details the work of Jasper Rine, UC Berkeley professor of molecular and cell biology, and his colleagues.

What Rine and colleagues found and report in the online early edition of the journal Proceedings of the National Academy of Sciences (PNAS) is that there are many genetic differences that make people's enzymes less efficient than normal, and that simple supplementation with vitamins can often restore some of these deficient enzymes to full working order.

First author Nicholas Marini, a UC Berkeley research scientist, noted that physicians prescribe vitamins to "cure" many rare and potentially fatal metabolic defects caused by mutations in critical enzymes. But those affected by these metabolic diseases are people with two bad copies, or alleles, of an essential enzyme. Many others may be walking around with only one bad gene, or two copies of slightly defective genes, throwing their enzyme levels off slightly and causing subtle effects that also could be eliminated with vitamin supplements

The twist in the research is that it was conducted by inserting human genes into yeast. However,

Rine and Marini are confident the results will hold up in humans. Their research, partially supported by the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army, may enable them to employ U.S. soldiers to test the theory that vitamin supplementation can tune up defective enzymes.

"Our soldiers, like top athletes, operate under extreme conditions that may well be limited by their physiology," Rine said. "We're now working with the defense department to identify variants of enzymes that are remediable, and ultimately hope to identify troops that have these variants and test whether performance can be enhanced by appropriate supplementation."

Marini and Rine estimate that the average person has five rare mutant enzymes, and perhaps other not-so-rare variants, that could be improved with vitamin or mineral supplements.

"There are over 600 human enzymes that use vitamins or minerals as cofactors, and this study reports just what we found by studying one of them," Rine said. "What this means is that, even if the odds of an individual having a defect in one gene is low, with 600 genes, we are all likely to have some mutations that limit one or more of our enzymes."

 I was pleased to note:

Marini and Rine credit Bruce Ames, a UC Berkeley professor emeritus of molecular and cell biology now on the research staff at Children's Hospital Oakland Research Institute, with the research that motivated them to look at enzyme variation. Ames found in the 1970s that many bacteria that could not produce a specific amino acid could do so if given more vitamin B6, and in recent years he has continued exploring the link between micronutrients and health.

Ames was one of my advisors during my PhD work at Johns Hopkins. 

Before you consider sending your DNA to some testing laboratory, you should know that the researchers cited in this article emphazise the great variety of gene versions that can be found even for a single gene.

Using DNA samples from 564 individuals of many races and ethnicities, colleagues at Applied Biosystems of Foster City, Calif., sequenced for each person the two alleles that code for the MTHFR enzyme. Consistent with earlier studies, they found three common variants of the enzyme, but also 11 uncommon variants, each of the latter accounting for less than one percent of the sample.

The researchers found that four different mutations affected the functioning of the human enzyme in yeast. One of these mutations is well known: Nearly 30 percent of the population has one copy, and nine percent has two copies.

The researchers were able to supplement the diet of the cultured yeast with folate, however, and restore full functionality to the most common variant, and to all but one of the less common variants.

Since this experiment, the researchers have found 30 other variants of the MTHFR enzyme and tested about 15 of them, "and more than half interfere with the function of the enzyme, producing a hundred-fold range of enzyme activity.

The researchers predict that the results will be applicable to humans.  I believe I've read differently lately; I'll check on that and report on it in another blog entry.

The only companies offering genetic testing online that may offer an analysis detailed enough to identify the particular variant of the MTHFR gene that one individual possesses are those charging about $30,000. And, their reports generally do not offer interpretation, only sequences of your particular DNA. I'm not even sure whether they even analyze both strands of DNA.

Last, we have an article from the Sacramento Bee titled, Genetics may define diets of the future. This is another report, from a different slant, on the meeting held at UC Davis in October of 2007. The article notes: "A few companies have already begun offering diets based on genetic testing for the general public" and then dashes it all by adding that UC Davis's Ray Rodriquez dismisses [these companies] as "infotainment.He adds, "It's not that the science behind them is bad or sloppy, he said. It's simply that so far, we don't know enough yet to leap from a few genetic details to truly individualized diets."

I think my favorite comment came from Jim Kaput, who recently took over as head of the U.S. Food and Drug Administration's division of personalized nutrition and medicine. "The fast-growing field will be huge. We are definitely not ready for it." Try saying his name outloud and you'll understand why I laughed. Regardless, I agree wholeheartedly.

Marie Godfrey, PhD





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