From Paradoxical Pyridoxine to “Glyconutrients”

“How wonderful that we have met with a paradox. Now we have some hope of making progress,” spoken nearly a century ago by Niels Bohr, the physicist.

Another name for pyridoxine is vitamin B6, and it is paradoxical. Its symptom of deficiency (neuritis) is the same as its symptom of excess. As it comes from nature it may be in an inactive form and must be chemically modified in the liver in order to have its beneficial effect. When pyridoxine is present in great excess (50 to 100 times the minimum requirement for optimum health), the mechanism for activation in the liver is overwhelmed, the inactive form begins to circulate in the general circulation, and poisons the enzyme system which pyridoxine normally enhances. Remember that all the blood from the stomach and the intestines goes through the liver before entering the general circulation. Thus any amount of pyridoxine obtainable from natural sources is not nearly enough to cause any problem.

Is it also paradoxical that the FDA’s (Food and Drug Administration) jurisdiction of dietary supplements was removed by Congress in 1994 except for cases of death or severe injury? What happened in 1994 that the FDA ceased to have jurisdiction over dietary supplements? The FDA had proposed to limit the per tablet dose of non-prescription vitamins to two or three times the daily requirement. This accorded with the precautionary principle, which holds that a measure of little cost and potentially great benefit can usefully be adopted without absolute proof of efficacy. There had also been some concern about harmful effects of even moderate doses of vitamin A and its precursors when administered as dietary supplements. The health food industry responded with campaign contributions to congressmen of both parties and requests to their customers to write to the congress. The voices of the FDA and interested experts were drowned in a flood of dollars.

In 2003 several deaths did occur from Ephedra, an otherwise useful herb that was being used to enhance athletic performance and Ephedra was belatedly removed from the list of permitted dietary supplements. Ephedrine, the active ingredient of Ephedra, has long been known to be very similar chemically and in action to amphetamines and therefore potentially hazardous—these deaths and the delay in regulating Ephedra should have been entirely sufficient grounds for fully restoring this jurisdiction to the FDA. (Ephedra is the name of a genus of plants, all species of which contain ephedrine. Generic names are always capitalized—species names are lower case.)

The most recent controversy about food additives is described in a three page article in Science for November 2, 2007, entitled “Who Owns Glycobiology?”—the study of glycoproteins (proteins combined with sugars). The article describes a controversy surrounding several conferences of glycobiologists sponsored by the manufacturer of Ambrotose, the company’s flagship “glyconutrient” This company had $400 million in sales last year. It is known that glycoproteins are prevalent in living creatures of all types, that we can make them in our bodies in all needed quantities (compare with lecithin), and they are quite harmless. (incidentally, glucosamine is a glycoprotein—harmless but with no proven benefit). The objectors feared that this particular company’s sponsorship of their conference would taint glycobiology with charlatanism. Particularly alarming is that articles are appearing in various venues, some quasi-scientific, implying that glyconutrients are essential for human health. From the Ambrotose website: “{eight sugars} are needed at the cellular level for optimum immune function {but that} six of these dietary glyconutrients…are often lacking in our modern diet,” glossing over the fact that all these glycoproteins can be manufactured in our bodies in any needed amount without any specific dietary source. On the other hand the attorney general of Texas in July, 2007, charged the company with violating Texas laws and is suing to stop its sales associates from making claims that its products cure diseases.

Now the public spends billions of dollars per year on unproven "alternative" remedies, an order of magnitude more than the cost of national campaign expenses. I am sure that other special interests, not in my sphere of knowledge, are achieving similar "success." Here is an example well known to me. Industry has doggedly succeeded in retaining the right to sell antibiotics for “growth promotion” in animal husbandry in spite of 50 years of the knowledge that this is a major source of antibiotic resistant bacteria. The mechanism of the growth promotion is that antibiotics are a partial compensation for unhygienic conditions where the animals are confined. Public financing of elections could be a real bargain. Maine has had voluntary campaign expense limitations for several years. If a complying candidate is outspent by an opponent not abiding by the limitation, Maine will make up 80% of the difference in spending. Already nearly 90% of candidates for statewide office have accepted spending limits there.

The cleanest solution to these problems of public information and safety is to restore something similar to the regulatory power the FDA lost in 1994. Since then, as mentioned in connection with the Ephedra disaster, sale of dietary supplements without FDA approval is allowed provided that no therapeutic benefit is claimed and no death or serious reactions are reported. Meanwhile we depend on the dietary supplements industry’s common sense not to promote excessive doses. (The industry, as a matter of self interest, has ceased recommending excessive doses of Vitamins A and D, fat soluble vitamins that accumulate in the body on repeated dosing. That does not stop unbridled promoting of lecithin—very near to no toxic hazard whatsoever, and no benefit whatsoever—blatant charlatanism. The glycobiology scientists are correct in not wanting to be co-opted in perpetrating fraud. The long tradition of pharmaceutical support for physicians’ continuing medical education for what were/are (shamefully) similar reasons is steadily withering and, I am pleased to report, at the medical profession’s behest.

The bottom line: “All substances are poisons. There is none which is not a poison. The right dose differentiates a poison and a remedy.” This is from Paracelsus who lived from 1493 to 1541—we stand on the shoulders of giants. Specifically: the Food and Nutrition Board of the Institute of Medicine, which is affiliated with and receiving funding from various federal agencies (such as the FDA, USDA, NIH, CDC) recommends that daily supplements of pyridoxine be limited to 100 mg per day because this is below the level where toxicity has ever been reported, and no studies have shown higher doses to have any increased benefit.

John A. Frantz, MD

November 30, 2007.

References

1) SchaumbergH et al. Sensory neuropathy from pyridoxine abuse: a new megavitamin syndrome. NEJM, 309, 445- 8 1983

2) SilvaCD. D’CruzFP. Pyridoxine toxicity courtesy of your local health food store. Ann Rheum Dis. 2006 Dec. 65(12) 1666-7

3) OmennGs et al. Effects of combinationof beta carotene and vitamin A on lung cancer and cardiovascular disease. NEJM. 1996 May2: 334 (18): 1150-5

4) KaiserJ. Who owns glycobiology. Science. 2007 Nov2: 318, 733-7