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Brian Leibovitz, Ph.D. Journal of Optimal Nutrition, 2552 Regis Dr., Davis, CA 95616.
This page contains the following articles:
JON Vol. 3(3), 1994 Editorial Brian Leibovitz, Ph.D.
The use of nutritional supplements in the treatment as well as prevention of disease, is clearly the future of medicine. Nutrition is currently going through a renaissance, and the prospects for alleviating suffering and improving the quality of life are very real, and have generated an excitement heretofore unknown. It's not just in the laboratories; clinicians are finding that nutrient and herbal supplements are indeed quite effective if the proper combinations at the proper doses are provided to the appropriate sites.
I'd like to present a novel nutritional therapy that is remarkably effective in the treatment (as well as the prevention) of heart disease. This empirical, but effective, formulation aptly illustrates the three fundamental principles of nutritional therapeutics: type, dose, and site.
Cardiac insufficiency (with its plethora of symptoms, including arrythmias, pulse abnormalities, pressure on the chest, difficulty breathing, and a sense of something being wrong in the area of the heart) is a condition which, if left untreated, will result in a heart attack. Although there are many causes of cardiac insufficiency (i.e., atherosclerosis, ischaemia, vasospasm), the ultimate biochemical defect is an insufficient supply of cellular energy (i.e., ATP). The combination of L-carnitine, coenzyme Q10, magnesium, and vitamin E (CCME) is an extremely effective treatment for cardiac insufficiency, as the nutrients provided cover most of the known mechanisms of cardiac dysfunction.
L-Carnitine, coenzyme Q10, magnesium, and vitamin E all interact in the mitochondrial generation of energy. Carnitine carries fats across the inner membrane for beta-oxidation. Coenzyme Q10 is the key factor in the electron transport system. Magnesium is an essential cofactor for many of the enzyme systems which support energy production. Moreover, it is required for ATP stability, as ATP is synthesized as the magnesium complex. Vitamin E is in the membrane where it can scavenge the free radicals generated by the electron transport system.
Lipids provide 60-80% of the metabolic energy required by the heart, which explains why such high levels of L-carnitine are stored in cardiac muscle. Moreover, interference with fatty acid oxidation can have dire consequences on myocardial function. Cognizance of L-carnitine’s import has led to numerous investigations, the results of which have documented its cardiovascular benefits in both animals , and humans , , Carnitine is perhaps best known for its lipid-lowering activity, specifically, its ability to rapidly and markedly decrease plasma triglycerides and increase HDL-cholesterol.
"Intravenous magnesium sulfate is a simple, safe, and widely applicable treatment. Its efficacy in reducing early mortality of myocardial infarction is comparable to, but independent of, that of thrombolytic or antiplatelet therapy."
These findings have been confirmed and reconfirmed in many clinics and laboratories. Teo and colleagues, for example, in an analysis of seven clinical studies, concluded that magnesium (in doses of 5-10 grams by intravenous injection) reduced the odds of death by an astounding 55%.
Studies of magnesium have revealed it to be Nature's "calcium-channel blocker" ; unlike its drug counterparts, however, magnesium has no toxic side-effects. Another important effect of supplemental magnesium is its ability to mitigate the cardiotoxic effects of catecholamines. Prielipp and associates, for example, published results of a clinical trial in which magnesium (10 mg per kg body weight per hour, or approximately 700 mg per hour for an average adult) attenuated the cardiotoxic effects of epinephrine in 17 bypass patients. Interestingly, the drug captopril - an angiotensin- converting enzyme (ACE) inhibitor - has been demonstrated to work by raising intracellular magnesium.
Vitamin E also plays a pivotal important role in the inhibition of platelet aggregation. Platelets aggregate because arachidonic acid is converted into pro-aggregatory thromboxanes; this conversion is an oxidative process responsive to vitamin E treatment. The ability of vitamin E to inhibit platelet aggregation is vitally important, as excessive, uncontrolled platelet aggregation is now acknowledged to be a primary causative factor in myocardial infarction. An ancillary mechanism involves vitamin E's ability to block redox cycling of catecholamines —the net result being a diminution in abnormal sympathetic stimulation of the heart.
CCME is, however, therapeutically effective; more importantly, it is practical, and hence patient compliance is not a problem. CCME is completely safe, and no toxic side-effects have ever been reported (save for the laxative effect of magnesium salts). The icing on the cake is that CCME - in addition to being effective and safe - is very inexpensive as compared with currently prescribed drugs. CCME;s cost efficacy is even more impressive when compared to mechanical procedures (e.g., heart transplantation and bypass surgery) that are major contributors to the spiraling cost of health care. CCME is effective, easy, and economical; what more could one possibly expect in clinical medicine?
Table 1. CCME: Recommended Doses For Prevention And Therapy Of Cardiovascular Diseases
Nutrient Preventive dose* Therapeutic dose* Major effects L-Carnitine (mg) 1,000 2,000 ATP beta-oxidation ¯ blood and tissue triglycerides Coenzyme Q10 (mg) 200 400 ATP, antioxidant Magnesium (mg) 600 1,200 Calcium-channel blocker ATP stability ¯ catecholamine damage Vitamin E (IU) 1,000 2,000 Antioxidant, ¯ platelet aggregation, ¯ thromboxane and prostacyclin ¯ leukotriene-mediated inflammation *Recommended daily intake based on a body weight of 70 kg.
DISCLAIMER
These recommendations are based on studies published in peer- reviewed, scientific journals. I am not a physician, having earned a Ph.D. degree from the Department of Zoology & Physiology, University of Wyoming. I am not an M.D., and hence cannot engage in the practice of medicine.
Suzuki Y, Kamikawa T, Yamazaki N. Effect of L-carnitine on cardiac hemodynamics. Japanese Heart Journal 22: 219-225, 1981. Challoner D, Mandelbaum I, Elliott W. Protective effect of L-carnitine in experimental intoxication with diphtheria toxin. Journal of Laboratory and Clinical Medicine 77: 616-622, 1971. McFalls E. Carnitine protection against adriamycin-induced cardiomyopathy in rats. Life Sciences 38: 497-505, 1986. Kamikawa T, Suzuki Y, Kobyashi A, et al. Effects of L-carnitine on exercise tolerance in patients with stable angina pectoris. Japanese Heart Journal 25: 587-597, 1984. Rebuzzi A, Schiavoni G, Amico C, et al. Beneficial effects of L-carnitine in the reduction of the necrotic area in acute myocardial infarction. Drugs Exptl Clin Res 10: 219-23, 1984. Vacha G, Giorcelli G, Siliprandi M, et al. Favorable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: decisive role of low levels of high-density lipoprotein-cholesterol. American Journal of Clinical Nutrition 38: 532-540, 1983. Pola P, Savi L, Grilli M, et al. Carnitine in the therapy of dyslipidemic patients. Current Therapeutic Research 27: 208- 216, 1980. Ferrari R, Cucchini F, Visioli O. The metabolic effects of L-carnitine in angina pectoris. International Journal of Cardiology 5: 213-216, 1984. Kishimoto C, Tamaki S, Matsumori A, et al. The protection of coenzyme Q10 against experimental viral myocarditis in mice. Japanese Circulation Journal 48: 1358-1361, 1984. Kamikawa T, Kobayashi A, Yamashita T, et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. American Journal of Cardiology 56: 247-251, 1985. Judy W, Hall J, Toth P, et al. Long term management of end stage heart failure with coenzyme Q10, IN "Biomedical and Clinical Aspects of Coenzyme Q," Volume 5, K. Folkers and Y. Yamamura (editors) Elsevier Science Publishing Company, Inc., New York, 1986, pp. 291-302. Goldenberg I, Cohn J. New inotropic drugs for heart failure. Journal of the American Medical Association 258: 493-496, 1987. Anon. Magnesium for acute myocardial infarction? The Lancet 338: 667-668, 1991. Durlach J. New trends in international magnesium research. Magnesium Research 5: 23-27, 1992. Woods KL, Fletcher S, Roffe C, et al. Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). The Lancet 339: 1553-1558, 1992. Teo KK, Yusuf S, Collins R, et al. Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomized trials. British Medical Journal 303: 1499-1503, 1991. Touyz RM. Magnesium supplementation as an adjuvant to synthetic calcium channel antagonists in the treatment of hypertension. Medical Hypotheses 36: 140-141, 1991. Prielipp RC, Zaloga GP, Butterworth JF, et al. Magnesium inhibits the hypertensive but not the cardiotonic actions of low-dose epinephrine. Anesthesiology 74: 973-979, 1991. O’Keeffe S, Grimes H, Finn J, et al. Effect of captopril therapy on lymphocyte potassium and magnesium concentrations in patients with congestive heart failure. Cardiology 80: 100-105, 1992. Ferrari R, Curello S, Boffa GM, et al. Oxygen free radical-mediated heart injury in animal models and during bypass surgery in humans: effects of alpha-tocopherol. Annals of the New York Academy of Sciences 570: 237-253, 1989. Esterbauer H, Striegl G, Puhl H, et al. The role of vitamin E and carotenoids in preventing oxidation of low density lipoproteins. Annals of the New York Academy of Sciences 570: 254-267, 1989. Jandak J, Steiner M, Richardson PD. Reduction of platelet adhesiveness by vitamin E supplementation in humans. Thrombosis Research 49: 393-404, 1988. Fukuzawa K, Kurotori Y, Tokumura A, et al. Vitamin E. Deficiency increases the synthesis of platelet-activating factor (PAF) in rat polymorphonuclear leukocytes. Lipids 24: 236-239, 1989. References Cited
JON 3(2), 1994 Editorial Brian Leibovitz, Ph.D. THE ABC/s OF CONFUSION AS A WEAPON: Acronyms, b-Carotene, And Capsaicin
This paper, published in Nutrition Reviews, introduced novel acronyms as well as toxicology acronyms adapted for nutrition:
Hathcock's definitions and calculations were equally unenlightening and senseless - not to mention confusing:
"For calculation of the RfD, the SF has been refined into multiple components described as uncertainty factors, UFs, and a modifying factor, MF. Thus, the RfD is defined by the following equation: RfD = NOAEL (or LOAEL) / (UF x MF), where UF represents one or the product of several uncertainty factors [emphasis added], generally tenfold each. An additional factor, the MF, is used as necessary to account for areas of uncertainty that are not explicitly addressed by the usual factors [emphasis added]."The scientific translation: agree on the policy (results) prior to conducting the research. Furthermore, why should "groups responsible for nutrition and health policy" - not bonafide nutritional scientists - be the final arbiters of scientific truth?"To assess the comparative safety of nutrients, a nutrient safety index (SI) has been defined as a ratio that is analogous in several ways to the therapeutic index (TI) for drugs. The SI was defined as the minimum toxic dose divided by the recommenced intake: SI = LOAEL / RI. This SI is useful for comparing the relative hazard posed by overconsumption of different nutrients. In this analysis, an SI of 10 does not indicate that an intake of up to 10 times the RDA is safe. Instead, it indicates that such an intake provides no margin of safety [emphasis added]." "If appropriate and adequate human data are available, a safety limit (SL) could be calculated as follows: SL = LOAEL / SF where LOAEL is the lowest-observed-adverse-effect level derived from clinical reports and SF is a safety factor that provides an acceptable margin of safety. The SF could be either fixed or variable [emphasis added]."
"Safety limits may be calculated by the SRM [square-root method] and MPM [midpoint method] as follows: Midpoint method:
SL = (LOAEL - (LOAEL - RDA) /2)) or equivalently SL = (LOAEL + RDA) divided by 2 x (the arithmetic mean) Square-root method: SL = (LOAEL / SF) = LOAEL / SI0.5 where SI = LOAEL / RDA or equivalently SL = (LOAEL x RDA)0.5 (the geometric mean).”"The confidence in and reasonableness of safety limits, regardless of the method used to define them, will be enhanced if the objectives [emphasis added], data criteria, and the quantitative method have been agreed upon ahead of time by groups responsible for nutrition and health policy [emphasis added]."
Even Science (the most widely-read scientific journal) got into the act. "b-Carotene: Helpful or harmful?" (3) was the title of a recent editorial which concluded that the NEJM study provides "support for skepticism, and a moratorium on unsubstantiated health claims about b-carotene and other antioxidants." This editorial also stated that, "A more frightening explanation is that b-carotene itself is carcinogenic... In light of the Finnish results, is it safe to expose thousands of people to large doses of b- carotene?"
The NEJM article has successfully introduced an element of doubt regarding nutrient supplements that will linger long after the study has been thoroughly discredited. Therein lies the real danger: "confusion as a weapon" accomplished via "science by design."
The concept of confusion as a weapon is described above, and was detailed in my article "Nutrition: At the crossroads" (4). Examples include: the oat bran study; the PDCAAS (the new measure of protein quality); the RDI, PDV, and DV (nutrient requirement and labeling acronyms); Chaparral-induced "hepatotoxicity"; and L-tryptophan as the cause of the Eosinophilia Myalgia Syndrome (EMS).
Sadly, this paper has undoubtedly confused many people about the value, and safety, of b-carotene (and other nutrient) supplements. Confusion, in turn, acts to decrease supplement usage. This is really an example of "science by design."
The NEJM study is a travesty of science - an experiment designed to fail - and does not deserve the honor of our speculation about possible mechanisms for its flawed findings.
b-Carotene supplements provided only 20 mg/day - far too low a dosage to expect beneficial effects (especially in a challenged system, as described below). The investigators should have used at least 140 mg/day of b-carotene, as these intakes have proven effective.
The dose of vitamin E was even worse — a measly 50 mg (or 50 IU) per day of dl-a-tocopheryl acetate! This is not even twice the RDA for vitamin E - hardly a therapeutic amount! The intake of vitamin E should have been in the 1,500 - 2,500 IU/day.
The effectiveness of any given dose, naturally, depends on the system. Heavily challenged systems, like smoking 20 cigarettes a day for 36 years (as in the present study), require intakes higher than the therapeutic doses routinely used. Because of its lack of applicability to the real human predicament, this article is not worth the paper it's printed on.
"The participants were randomly assigned to one of four supplementation regimens: a-tocopherol alone (N=7286), a- tocopherol and b-carotene (N=7278), b-carotene alone (N=7282), or placebo (N=7287). Thus, a total of 14, 564 men received a- tocopherol, and 14, 560 received b-carotene."Thus, any benefits of one nutrient (e.g., vitamin E alone) would be masked because the "without vitamin E" group contained data from those given b-carotene alone and from placebo-treated subjects. Incidentally, there was no mention of what placebo was used. They did, however, point out that "all formulations were colored with quinoline yellow" (a synthetic food dye with known toxicity) (5).
"In light of all the data available, an adverse effect of b-carotene seems unlikely; in spite of its formal statistical significance, therefore, this finding may well be due to chance."
This statement is an oxymoron: statistical significance, by definition, means that the results are not due to chance. If the authors don't even believe their own data, why should anyone else have confidence in their findings? The statement above is a type of academic insurance - insurance against the likelihood of being proven wrong about b-carotene and lung cancer.
"The Adjunct To NSAIDs That Works [emphasis added]"The obvious implication is that other approved adjuncts don't work. The details were on the second page of the advertisement.
"Zostrix works safely and economically. Zostrix is free from systemic side effects, and has no known drug interactions. When used properly, Zostrix is inexpensive pain therapy. In fact, when treating a single knee joint, a 20-gm tube can last up to a month."
There is no problem with the concept of using capsaicin to treat inflammation; the data clearly show that it is effective for inflammation as well as pain relief (via a reduction in the levels of substance P). The concentration of capsaicin, however, is extremely low (0.025% by weight); hence, Zostrix is simply a very diluted form of this remarkable non- vitamin nutrient.
Cayenne pepper contains not less than 0.5 (dry weight) of capsaicin. A small, inexpensive (~$2) bottle (45.4 gm) of Cayenne at the grocery store contains ~227 mg of capsaicin. A similar amount is provided by ~45 tubes of Zostrix® (each 20-gm tube contains 5 mg capsaicin). The cost of 45 tubes - at $15.50/tube - is $698.
Thus, ~$2 worth of Cayenne pepper yields ~$700 worth of Zostrix. This astronomical markup of approximately 350-fold (35,000 percent) is yet another example of a nutrient (or herb) being converted to an expensive prescription item. FDA restrictions on Cayenne are likely, as the sales of Zostrix will suffer if the non-prescription form is allowed to remain on the market. The confusion, in the Cayenne pepper caper, is due to nomenclature: the name Zostrix's offers no clue as to the origin or nature of its active component.
Hathcock, JN. Safety limits for nutrient intakes: concepts and data requirements. Nutr Rev 51: 278-285, 1993. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. The effect of vitamin E and b-carotene on the incidence of lung cancer and other cancers in male smokers. New Engl J Med 330: 1029-1035, 1994. Nowak R. b-Carotene : Helpful or harmful? Science 264: 500-501, 1994. Leibovitz B. Nutrition: At the crossroads. J Optimal Nutr 1: 69-83, 1992. Budavari S, O’Neil MJ, Smith A, et al. (editors). The Merck Index, 11th Edition, Merck & Co., Inc., Rahway, NJ, 1989, pg. 1286. The New England Journal of Medicine, December 9, 1993. REFERENCES CITED
The future is what we make it, and is molded by today’s thoughts and tomorrow's actions. As I see it, nutrition is at a crucial junction from which there are two possible directions: 1) one in which nutrients are extensively used to prevent and treat human diseases, and 2) one in which the therapeutic applications of nutritional supplements continue to be ignored.
I started this article with the intention of discussing all the players, concepts, and events. There is simply too much to cover, however, and some of the topics will have to wait for future issues.
Equally important, I am not required (nor have I ever been asked) to write or speak about any nutrient or product which, in my opinion, lacks sufficient documentation. Consequently, I have no vested interests whatsoever, which allows me to maintain objectivity. Those who are familiar with the health food industry know how very rare this relationship really is.
My only goal is to help speed the day when nutritional supplements are used to the fullest extent possible to reduce the morbidity and mortality of human diseases and to improve the quality of life.
Compared to placebo, milrinone therapy resulted in a 28 percent increase in mortality from all causes (P = 0.038) and a 34 percent increase in cardiovascular mortality (P = 0.016).
Furthermore, milrinone significantly increased the number of serious adverse cardiovascular reactions and also hospitalizations as compared with the placebo group (1). Nice drug!
An increase in mortality after treatment with cardiac drugs is the rule, not the exception. Consider the drug clofibrate, a lipid-lowering drug prescribed for millions of men world-wide. In a six-year, World Health Organization (WHO) study of 5,000 patients with known coronary heart disease, clofibrate-treatment resulted in a 44% higher mortality rate as compared to placebo (2).
Side Effects. In addition to higher mortality rates, most cardiac drugs produce a plethora of harmful side-effects. Consider the drug Plendil (felodipine), a calcium channel blocker. In the latest issue of NEJM, an advertisement for Plendil lists over 15 adverse reactions at a dose of 5 mg (in percent of patients), including: peripheral edema (22%); headache (19%), flushing (6%), dizziness (6%), upper respiratory infection (6%), and palpitation (2%). Moreover, the toxicity of Plendil is dose-dependent: at a 20 mg dose, the incidence of peripheral edema is 36%, palpitation 12%, headache 28%, and flushing 20%. The advertisement also stated that Plendil's "safety in patients with heart failure has not been established".
Imagine the FDA's reaction to a nutrient that produced such an array of untoward side-effects! The FDA would undoubtedly deem it toxic and ban its sale. Recall that guar gum (a soluble fiber) was banned from weight-loss products by the FDA because a few individuals didn't dilute it properly and choked (the FDA never said how many people, nor did they mention the outcome).
It's no joke that the average drug advertisement has one sentence of indications followed by a full page (sometimes more) of contraindications, warnings, precautions, adverse reactions, and toxic effects.
Leaving drugs for a moment, other treatment modalities of modern cardiovascular medicine are even more deranged. Artificial hearts, for example, are even further removed from the ultimate management of cardiovascular diseases. In a recent review of the artificial heart program, a blue-ribbon panel from the Institute of Medicine concluded "the projected costs would be greater, and the benefits lower, than for any medical procedure now in use, but that research should go on anyway" (3).
These drugs, by-and-large, are the worst chemicals on the shelf; they work by damaging the DNA of fast-growing cells, thereby inhibiting growth potential. That’s fine for tumor cells, but the indiscriminate toxicity of these anti-metabolites also obliterates cells in the gastrointestinal tract, bone marrow, mucous epithelium, hair, and the immune system (particularly those involved in anticancer and antimicrobial immunity). The non-specific nature of chemotherapy results in severe gastrointestinal damage, malnutrition, anemia, loss of hair, and immune dysfunction. Naturally, death from bacterial or other infections is common in cancer patients given chemotherapy; estimates of infection as the proximate cause of death in cancer patients range from 50% (in those with solid tumors) to 75% (in leukemia patients) (4).
In a recently-published review of the book "Cancer Risk After Medical Treatment", the Dr. Penn (the reviewer) observed that:
"It is one of the great paradoxes of medicine that the treatment of cancer may be complicated by the development of a second type of cancer induced by radiotherapy, chemotherapy, or both treatments. There is an increased risk of acute non- lymphocytic leukemia after treatment with a variety of alkylating agents and an increased risk of carcinoma of the bladder after treatment with cyclophosphamide" (5).
In another article published recently in NEJM, continuous combination chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) was compared to no treatment in 250 women with metastatic breast cancer (6). The results: chemotherapy did not improve survival, but it did significantly decrease the quality of life (as evidenced by an increased frequency of vomiting, nausea, mucositis, and other "side- effects" of these noxious poisons).
Another class of chemotherapy agents is based on adriamycin (aka doxorubicin). Adriamycin works by redox cycling, thereby generating copious quantities of free radicals which overwhelm defense systems of cancer cells as well as cells in the heart. Not surprisingly, adriamycin is very cardiotoxic, and approximately 10-15% of cancer patients given this drug die from cardiomyopathy (7). In fact, adriamycin is so effective (meaning cardiotoxic), it’s become a favorite model system for many laboratories studying oxidative damage and antioxidants.
The bottom line is that the twenty-year, $22 billion dollar war on cancer has failed to produce any real benefits. As discussed in a recent issue of Science , "Overall death rates from many common cancers remain stubbornly unchanged -- or even higher than when the war began" (8). Dr. Samuel Epstein and 60 physicians and scientists -- at a press conference in Washington D.C. -- charged that the cancer establishment repeatedly and grossly exaggerated its’ ability to treat and cure cancer:
"The cancer establishment confuses the public with repeated claims that we are winning the war...Our ability to treat and cure most cancers has not materially improved"(9).
If the medications presently used to treat the major diseases were truly efficacious, then why are cardiovascular diseases, cancer, and lung diseases still the leading causes of death?
The cold, cruel fact is that -- despite the highly-proclaimed advancements in medicine -- many hundreds of thousands of Americans die each year because they are given the wrong medicines.
Aside from emergency medicine, diagnostics, orthopedics, and certain other specialties, modern medicine has simply missed the forest for the trees. I would be remiss in not mentioning The National Cancer Institute (NCI)-- a remarkable exception. NCI is currently supporting some 40 studies on the anticancer effects of a variety of nutrient supplements (vitamin A, beta-carotene, vitamin C, vitamin E, selenium, folic acid, and others).
Most other branches of medicine, however, have been slow to recognize the value of supplementation. This is particularly true of the heart disease establishment, which is trapped in the dogma about polyunsaturated fatty acids (PUFAs) of the omega-6 series being of benefit in treating coronary heart disease. That fantasy, plus the idea that cholesterol per se is the cause of coronary artery disease, has been promulgated for so long, and with such fanaticism, that a retraction at this stage would involve a serious loss of credibility.
This prediction is based on several factors, the most important being the thousands of studies (published in respectable, peer-reviewed journals) which I've accumulated over the past 18 years. The volume of literature is incredibly large at present, and it's growing by leaps and bounds. I xerox 10-30 articles on supplements each week at the U.C. Davis Health Sciences Library. My collection of articles on nutrition and disease now fills 38 metal file cabinets (two 5-stack, six 4-stack, and two 2-stack file cabinets -- the 25"-deep kind).
I believe that nutrients -- especially micronutrients - - will be recognized as the medicines of choice, and that, ultimately, nutrients will supplant most drugs used in clinical medicine. The handwriting is clearly on the wall.
Most people think of nutritional supplements for the prevention of disease, which is fine as substantial data have accumulated in support of this concept. In real life, however, most people wait for the lumps, bumps, aches, and pains: it is a rare individual who actually has the foresight to use supplements prophylactically. Nutritional supplementation as a therapeutic modality is at least as important as it’s preventive roles. This topic has begun to be studied in earnest, and results document the benefits of increasing dietary intakes of nutrients in the treatment as well as prevention of numerous human diseases.
Non-Vitamin Nutrients: The Gray Area. This interface between vitamins and natural products includes coenzyme Q10, bioflavonoids, carotenoids, carnitine, and terpenes -- compounds which belong to a group I call "non-vitamin nutrients". These naturally-occurring compounds are not considered vitamins (except for some pro-vitamin A carotenoids); nonetheless, numerous beneficial effects are elicited by dietary supplementation with these remarkable molecules. The volume of the data is really quite astounding: articles about carnitine fill an entire file cabinet, as do the bioflavonoids; coenzyme Q10 and carotenoids fill yet another.
Bioflavonoids are probably the hottest class of non-vitamin nutrients, and their medical applications span almost every pathology and organ. Silybin, a flavonolignin complex isolated from Milk Thistle, was chosen as the cover molecule for this inaugural issue. In Europe, silybin is marketed as a drug for the treatment of cirrhosis. Like most bioflavonoids, it has potent antioxidant and metal-chelating properties; in addition, silybin raises liver glutathione levels.
"The conception that the investigation of the pure vitamin might possibly disclose new and so far unknown effects has proven especially productive with vitamin C. It appears that this vitamin given in pure form may influence disease conditions, which (so much may be said today) have nothing to do with states of avitaminoses or hypovitaminoses. Thus, the vitamins, beyond the service they render as accessory substances, possess the properties of curative stuffs [emphasis added]."This is a good description of JON's focus, namely, that dietary supplements of macronutrients and micronutrients are beneficial in the prevention and/or treatment of disease as well as in the maintenance of optimal health. So JON's unique focus is really based on ideas conceived over half a century ago. This is both a tribute to the early nutrition investigators and a reason for humility about the novelty of our conceptions. The interest and excitement in this field is blossoming as never before, as reflected by the present number of nutrition journals (>35), books (>50/yr), and conferences (>40/yr is a conservative estimate). The recent New York Academy of Sciences Conference entitled "Beyond Deficiency: New Views On The Function And Health Benefits Of Vitamins" (chaired by Drs. Machlin and Sauberlich) is further confirmation of the growing interest in nutritional supplementation.
The article covered free radicals/antioxidants and cancer, heart disease, aging, cataracts, birth defects, infectious diseases, and a host of other diseases. In addition, folic acid supplementation as a means of preventing neural tube defects in children was discussed, as was folate’s capacity to reverse precancerous lesions of the cervix .The increased requirement for vitamins and other nutrients with advancing age was also pointed out, as was the increased requirements for nutrients in persons taking various medications. The author hit the nail on the head in the summary statement:
"They [vitamins] may be much more important than doctors thought in warding off cancer, heart disease, and the ravages of aging -- and no, you may not be getting enough of these crucial nutrients in your diet."
The fact that Time Magazine went out on a limb with this provocative cover story indicates their lawyers felt the documentation was sufficient to protect against lawsuit. The NY Times also joined in with it's article entitled "Vitamins Win Support As Potent Agents Of Health" (NY Times, March 10, 1992). These were soon followed by an article in USA Today entitled "Megadose Vitamin C Linked To Longer Life" (USA Today, May 8-10, 1992). The latter report (published in Epidemiology) was based on a study of 11,348 U.S. adults, and revealed that men with the highest vitamin C intakes had a 35% lower mortality rate and a 42% lower death rate from heart disease and stroke (women had a 10% lower mortality rate and a 25% lower death rate from heart disease and stroke.
In fact, it seems everyone in the U.S. knows that nutritional supplements can be of benefit in disease prevention and/or treatment. Even the conservative dietitian at CNN (Carolyn O'Neil) brought up this concept when she reported that calcium intakes above the RDA could benefit those with high blood pressure.
Yes, most Americans are aware of nutrients' potential health benefits -- a concept whose time has indeed arrived. Most, that is, except those at the FDA who are entrusted with regulating the supplement industry.
Even stranger is that ineffective OTC supplements never seem to get noticed or hassled, such as diosgenin, gamma-oryzanol, Smilax, and other plant sterols which are marketed as anabolic agents. These ideas gave rise to the following principle:
The stronger the data supporting the efficacy of a nutritional supplement, the sooner it will be banned from over-the-counter sales.
Corollary: The drug derivative, however, will soon be widely acclaimed for its therapeutic value.
What was the heinous crime that led to this raid? Did Dr. Wright commit rape, child abuse, or murder? Was he selling crack or cheating on his income tax? Nope. Dr. Wright's crime was simply the possession of vitamins, specifically, an injectible mixture of B complex. If this is difficult to fathom, or evokes feelings of anger and frustration, relax. You're in good company. Intelligent people throughout the U.S. were, and continue to be, baffled by these unexplainable, objectionable, and possibly unlawful actions of the FDA.
What If... Imagine being arrested for possession of L-carnitine? Or six months hard labor for N-acetylcysteine, or L-arginine. Because its’ benefits are so well-documented, possession of coenzyme Q10 would probably get you two to four years in the Federal Penitentiary, assuming that was your first offense.
Where would it stop? We'd have to purchase our nutrients from shady characters on dark street corners. Of course, a black market would develop, with drug czars and all. Crime usually follows lucrative, illicit enterprises, so the number of murders and muggings would be bound to rise. The "vitamin pushers" -- once arrested -- would further overcrowd our already-overflowing jails. On Wall Street, the market would certainly suffer from the loss of U.S. dollars to foreign "vitamin kingpins". More police would have to be hired to assist the overburdened "supplement police", and the army would likely get diverted from the war on drugs to the war on vitamins. Naturally, taxes would have to be raised to pay for all this. And so on. This all sounds pretty silly until you realize that the FDA is well on its' way to implementing such a plan.
The "Great Vitamin War". The arrest of Dr. Wright did produce one unexpected benefit: it shocked us into doing something. Suddenly, people realized that action must be taken, and soon, to protect our rights to the unrestricted availability of nutrients and food factors, and to prevent FDA's strangulation of the supplement industry. The "Great Vitamin War", as it's been called, is on. In a way, after so many years of "cold war", the recent declaration is almost a relief.
The first breakthrough in understanding EMS came in July of 1990, when EMS was firmly linked to L-tryptophan from a single manufacturer (Showa Denko--a large Japanese chemical and pharmaceutical company) (12). Later studies revealed that suspect batches of L-tryptophan from Showa Denko contained an impurity which might be the cause of EMS. This impurity was isolated by high-performance liquid chromatography as "peak E", and was suggested to be the dl-tryptophan aminal of acetaldehyde (DTAA) (13). More recently, however, chemical and spectral studies have demonstrated that "peak E" is a tryptophan derivative called 1,1'-ethylidenebis[tryptophan] (14).
The presence of this toxic impurity has been linked to the use of a new, genetically-recombined strain of bacteria (Bacillus amyloliquefaciens, Strain V) in Showa Denko's lots produced between October 1988 and June 1989 (15). In addition, the toxic contaminant has been attributed to several changes in the purification procedures which were instituted during the time period in question. This former point raises serious concerns about the use of recombinant bacteria in fermentation technology. The FDA apparently did not learn the lesson of EMS, namely, that recombinant genetic techniques can produce novel toxins in our nutrient (or food) supply. If EMS was caused by consumption of gram quantities of genetically-recombined material (L-tryptophan supplements), what may happen when kg quantities of recombinant vegetables are eaten?
Be that as it may, the bottom line is that L-tryptophan per se is not the cause of EMS; this disease is due to the presence of a contaminant which resulted from inappropriate production and inadequate purification procedures (16). Clearly, production and purity standards need to be defined and implemented so that this kind of industrial mistake never happens again. With proper quality control protocols, there is no reason not to lift the ban.
To retain the ban on L-tryptophan supplements, however, is absurd in light of the fact that L-tryptophan is used every day in every U.S. hospital in total parenteral nutrition (TPN) solutions. TPN is given intravenously, and hence purity is even more critical than for oral supplements. If L- tryptophan is allowed for use in TPN solutions (where it is used as the free amino acid), then it would most certainly be safe given by the oral route.
And a final comment: L-tryptophan occurs in many foods, particularly protein-rich foods like steak and milk; humans consume 1-2 grams per day in the average diet. Should the FDA consider banning steak, milk, cheese or other foods rich in L-tryptophan? This argument is a reductio ad absurdum, but it does serve to illustrate the inherent fallacy in the FDA’s indictment of L-tryptophan.
The crucial point is that an amino acid (or other nutrient) which is essential for life in a given, nutritional quantity cannot, by definition, be toxic when consumed in such amounts.
What I'd really like to know is: how do they avoid seeing any of the thousands of articles published in the scientific literature? It must be a very special talent: only the FDA, Victor Herbert, Stephen Barrett, Frederick Stare, Richard Wurtman, and a handful of others believe that nutrient supplements are worthless except for treating nutritional deficiency diseases. It is very doubtful that one could spend 10 minutes in any Health Sciences Library periodicals room and not find at least one article about nutritional supplements benefiting some disease or condition.
In summer of 1991 while Editor-in-Chief of the Journal of Applied Nutrition, I wrote to Dr. Kessler, Gary Dykstra, and Dr. Vanderveen (Head of Nutrition at FDA) about joining my Editorial Board. By Autumn, I'd sent two letters and made dozens of follow-up calls to each of these FDA officials. In addition, I offered to send complimentary copies of all the nutrition articles I find in my weekly sojourns to the library. Not a bad offer, considering the large number of articles I always end up with.
Only Mr. Dykstra had the courtesy to respond to the Editorial Board invitation (he declined, of course). And none responded to my offer of free copies of the latest nutritional literature. Evidently, these top FDA officials aren't interested in learning about what they are regulating.
My experiences only confirm what is most Americans already know: The FDA is apparently not interested in an honest evaluation of the overwhelming amount of documentation regarding medical applications of nutritional supplements.
If you think the RDAs are bad, wait till you see the RDIs !! First off, there is only one RDI value for any nutrient, regardless of age, sex, or pregnancy/lactation. Worse, the RDIs are significantly lower than the RDAs (by 10-40 percent) for 16 nutrients. Biotin is down 40%, calcium by 25%, magnesium by 25%, vitamin A by 12%, thiamin by 20%, vitamin B-6 by 25%, and so on. A comparison of RDA and RDI values for selected nutrients is provided in TABLE 1.
Switching from RDAs (already low) to RDIs is analogous to reducing the definition of poverty to annual incomes of less than $1,000. The poor would cease to exist on paper, but in reality nothing would change. With the RDIs, dietary deficiencies may cease to exist simply because of how they are defined. More information on the RDI may be found in the article by Jeffrey Blumberg.
It's almost laughable, like a Charlie Chaplin movie; we’ve got, in addition to the RDA, the RDI, DRV, and PDV ("Percent of Daily Value", whatever that nonsensical term might be). In the midst of all these acronyms, I'd like to add one more: Generally Regarded As True (GRAT). The FDA needs to learn that, despite the RDA, RDI, DRV, PDV, GRAS or PDBCAA (see below), the therapeutic benefits of supplementary nutrients are GRAT.
However humorous this may seem, their strategy works. Make no mistake about it: the public, confused and bewildered by all these acronyms, simply gives up trying to understand nutrition.
It gets worse. FDA plans to set soy protein at a PDCAAS of 1.0 -- the top of the PDCAAS rating scale. More importantly, they state that:
"If a food has a PDCAAS above 1.0, then it shall be set at 1.0" (17).In other words, all higher-quality proteins (eg., lactalbumin, egg albumin, fish, or casein) will, by the FDA's definition, be equal to soy protein.
The only exception is in infant foods, where the PER will be retained and required for labeling purposes. The FDA must have realized that they'd have a lot of dead babies on their hands if they allowed the PDCAAS to replace the PER in infant formulas, since infants need higher- quality protein than soy can supply.
Incidentally, the article was written by Dr. E.C. Henley, Director of Nutritional Science at Protein Technologies International, Checkerboard Square, St. Louis. And the FDA’s decision to change the determination of protein quality was in response to a "citizen petition submitted by Protein Technologies International, Inc., (Docket No. 90P-0052)" (17). Could Ralston-Purina be looking to sell some soy protein? Soy is a good protein, to be sure, but it will never be as high-quality as lactalbumin -- no matter what it's PDCAAS rating.
If the FDA is ever allowed to change science to sell product -- the ultimate prostitution of science -- we are all in deep trouble.
In contrast, therapeutic applications of nutritional supplements can -- and are -- patentable (so-called "use patents"). Several nutritional entrepreneurs hold a number of these, but the King of use patents has to be Dr. Richard Wurtman -- a professor at the Massachusetts Institute of Technology. A recent search of U.S. patents revealed that Dr. Wurtman owns over 20 use patents on various medical applications of supplementary amino acids. Some examples include: L-tyrosine for increasing blood pressure (US Patent # 4,745,130), choline for neurological diseases and aging (US Patent # 4,737,489) or for enhancing muscular performance (US Patent #4,626,527), and L-tryptophan for increasing brain serotonin levels (US Patent # 4,687,763) or for reducing depression (US Patent #4,377,595).
This is the ultimate in hypocrisy. Wurtman states that all amino acids are toxic and should be taken off the OTC market; all the while he is secretly accumulating use patents so that when amino acids are removed (as appears imminent), he is ready to roll.
The problem with use patents, from the patent-holder's point of view, is that they are only salable if the nutrient in question cannot be purchased OTC. This is the rub, and probably explains Wurtman’s testimony before a House Subcommittee Hearing last year where he implored the Congress to ban OTC sales of amino acids. I particularly enjoyed his statement to the effect that "L-tryptophan has nothing to do with nutrition"; this comment is rather inane, considering the essentiality of this amino acid.
Unfortunately, Wurtman is not alone in his greed, and there seems to be a trend towards profiteering at the expense of the nation’s health. Dr. Stephen De Felice, for example, has long been trying to get carnitine removed from the OTC market, as his use patents can't be sold to drug companies (eg., Sigma Tau, which already markets a "drug" form of carnitine called Carnitor -- actually nothing more than L-carnitine at many fold the OTC price) until this is accomplished. I met De Felice in 1983 just prior to publication of my book on carnitine; I still remember him telling me what a great drug carnitine could be. De Felice's latest thing is "nutraceuticals" -- nutrients turned into pharmaceuticals. A recent paper describes De Felice’s so-called "White Paper" -- his "Nutraceutical Initiative: A Proposal For Economic And Regulatory Reform":
"A nutraceutical can be defined as any substance that may be considered a food or part of a food and provides medical or health benefits, including the prevention and treatment of disease. Nutraceuticals may range from isolated nutrients, dietary supplements, and diets to genetically engineered "designer" foods, herbal products, and processed products, such as cereals, soups, and beverages." (18).
Apparently, De Felice won't be satisfied with just getting carnitine classed as a drug; he wants it all -- vitamins, minerals, non-vitamin nutrients, herbs, foods, etc. I believe that De Felice has similar goals, namely, the use of nutrients for preventing and treating diseases; the only difference is that he wants to make his fortune selling us the nutrients at many fold their OTC price.
There are, of course, a number of easier ways to make a nutrient into a drug. You can oxidize it (retinoids), add a chlorine or two (4",6- dichloroflavan), methyoxylate it (glutathione monomethylester), dimerize it (sodium cromolyn) or acetylate it (acetyl-L-carnitine). You can even link it to another vitamin -- as in Juvela-Nicotinate (dl-alpha tocopheryl nicotinate) -- or non-vitamin nutrient, as in Hexopal (inositol nicotinate).
This is exemplified in an article by Victor Herbert appearing in the March/April issue of Nutrition Today (not peer-reviewed, despite Victor's criticism of such journals) (19). Victor Herbert has really outdone himself in this article which, in my opinion, is not even a reasonable facsimile of science. It certainly ranks among his worst, and that's saying quite a bit as Victor has penned some real dillies. Remember the fable about vitamin C destroying vitamin B12 in foods? That was one of Victor's contributions to nutrition. [NOTE: some textbooks, even today, still use B12 destruction as a "toxic effect" of vitamin C, even though it's been unequivocally disproved. The error, as it turned out, was that Victor used the wrong assay for vitamin B12].
Victor's "Medicolegal" Case Against OTC Amino's. There are so many errors that we’ll only be able to mention a few of the more important ones. Victor stated that "The potential toxicity of large doses of single amino acids led the FDA to remove these from the GRAS list in 1974." But where is the evidence of individual amino acid toxicity when given as oral supplements? Aside from EMS (a disease which was due to a contaminant in L-tryptophan supplements), his one reference to a peer- reviewed journal was a 1958 study by Fahey in which intravenous amino acids raised blood ammonia. His only other "reference" to amino acid toxicity is a book by none other than Richard Wurtman.
If amino acid toxicity was as well known as Victor implied, there must be some references in the literature. Why aren't more references cited by Herbert regarding amino acid toxicity? It's simple: there's virtually nothing to cite. Amino acids are not toxic despite proclamations by Victor Herbert, Richard Wurtman, or the FDA.
Although a number of false "toxic effects" were mentioned (like the unreferenced accusation that "large doses of L-tryptophan will block gluconeogenesis"), Victor missed the only real undesirable side-effect of aminos (diarrhea at very high intakes, as occurs with consumption of large amounts of any substance). Victor has consistently criticized the supplement industry for unsubstantiated claims; well, where is his proof? In his summary, Victor states that:
"Not only is there no need for free tryptophan in the diet, but free tryptophan is not recognized as safe by the Food and Drug Administration. It is a drug whose only use is as a drug or food additive (in infant formulas, medical foods, and as an additive to tryptophan-poor protein of plant origin)"(19).Without getting into the specifics of this moronic statement, I’d just like to know why, if free tryptophan is not recognized as safe by the FDA, it is being fed to babies and given to people as a drug?
Stonewalling In Academia. I have observed an incredible resistance to JON at the very top of the academic community. Both the American Journal of Clinical Nutrition and the Journal of Nutrition refused to run my “call for papers” notice (a paid advertisement). This is in spite of the fact that they had run the exact same ad for three and six months, respectively, the previous year (when I was Editor-in-Chief of The Journal of Applied Nutrition). [In truth, the ads were slightly different: The Journal of Applied Nutrition was changed to The Journal of Optimal Nutrition].
Neither AJCN nor JN responded in writing to my written requests, nor were any reasons given for their rejections. Even more lamentable was that I was not told how to change the ad to make it acceptable. All I got from JN was the proverbial run-around, and all I was told was that "someone had said they didn't like it". I tried, in vein, to find out more about how they had arrived at their decision by contacting Dr. Willard Visek (the Editor-in-Chief of JN). The irony was that I had been elected to the American Institute of Nutrition (JN's parent organization) the same week as the rejection occurred. Nice welcome!
The story at AJCN was much the same: Dr. Stephen Schiaffino (the Managing Editor of AJCN) said that he’d asked four individuals about this ad, and they all disapproved. When asked how many he had to choose from, his response was 500, but on further questioning he was unwilling to get any other opinions. In essence, I was told that 0.8% of the total reviewing board was sufficient to reject the JON “call for papers” ad. Further discussions with Dr. Norman Kretchmer (Editor-in-Chief of AJCN) were equally revealing. He told me that AJCN didn’t have to say why the ad was rejected, or let me know how it could be changed to make it acceptable, or even respond in writing!
One take-home lesson is that there is something amiss with the decision-making process at the very highest echelons of academic nutrition -- at levels I'd previously thought immune to petty politics and common corruption.
The Bottom Line: Fear. I also brought this up to illustrate the depth of resistance to any one or any group focusing on the science of nutritional supplements. I definitely got the impression that there was no way either JN or AJCN would carry the ad, not because of me personally, but because of what JON represents. But of greater import is the fear that gets registered every time the terms "science" and "supplements" are used in the same sentence.
Nutritionists are terrified of even appearing to be supplement- oriented, fearing (probably rightfully so) that their grants would be cut and their reputations ruined. At several free radical/antioxidant meetings, I have proposed that we (the leaders in antioxidant research) make some recommendations to the general public, as we have the knowledge (and responsibility) to do so. No recommendations ever emerged, however; the fear was simply too great. Moreover, several members of JON's Editorial Board have related instances where they have been warned not to publish positive results on supplemental nutrients, for by doing so their careers would suffer.
The fear of having one's career ruined is, in my estimation, one of the methods whereby the system has survived for so many years. It is this same system which promotes the use of the wrong medicines -- ones which at best are ineffective, at worst lethal. It is the same system which brings you the PDCAAS, the RDI, and genetically-recombined vegetables.
I believe that as nutritionists we can no longer hide behind the veil of academia; we must stand up for what we know to be the truth. If not, we are guilty of complicity with a deplorable system of medicine.
Mineral chelates, however, contain only 10-25% of the elemental mineral (on a weight basis). For example, calcium citrate is only 24%, calcium lactate only 18%, and calcium gluconate only 9% elemental calcium.
If all of Brand X's calcium were actually in the form of calcium citrate (with the highest percentage of calcium), the weight of 1 g elemental calcium would actually be about 4 g The total weight of their 1.7 g of elemental minerals would be at least 6.8 g. And that's giving them the benefit of the doubt by using citrate as the chelator.
False label claims like these damage the industry's credibility, and underscore the need for quality control in the health food industry. There's no reason why nutrient supplements cannot be prepared using the same, meticulous standards used by pharmaceutical companies. The industry as a group needs to set such standards and, more importantly, enforce them.
This statement is from Dr. Frederick Stare, but it could have come from anyone. This concept so well entrenched that no one even questions it's validity anymore. This is dogma as ingrained as that which once decreed the world is flat. Yes, the diet provides all one needs for preventing nutritional deficiencies, that is, for adequate health.
But that's as far as it goes. There is not a shred of evidence that diet alone can supply enough micronutrients to attain any level of health above adequate. I’ve never seen a single study to support the concept that you get everything you need for optimal health for a well-balanced diet. This is due, in part, to our asking the wrong questions. Instead of nutrient deficiencies, as we’ve studied for so long-- and as many nutritionists still study, we need to focus on supplemental nutrients, for only through supplemental nutrients can we achieve optimal health.
For it is my belief that nature, which wants us to reproduce and then die, ensures these events by limiting the number of micronutrients which may be obtained from our caloric intake. If one ate lemons all day, one might be optimal in vitamin C, bioflavonoids, and possibly terpenes, but deficient in everything else. And for the first time in Mankind’s history, we now have the knowledge and capabilities to extract these wondrous factors from foodstuffs, and ingest them in sufficient quantities to achieve a state of optimal health.
REFERENCES CITED 1. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 325: 1468-1475, 1991. 2. The National Cholesterol Education Program Expert Panel. Report on detection, evaluation, and treatment of high blood cholesterol in adults. arch int med 148: 36-69, 1988. 3. Marshall E. Artificial heart: the beat goes on. Science 253: 500-502, 1991. 4. Bodey G. Infections in cancer patients. Cancer Treatment Rev 2: 89-128, 1975. 5. Penn I. Review of “Cancer risk after medical treatment”, Coleman M, editor, Oxford University Press, NY, 1991. This review appeared in N Engl J Med 326: 1298-1299, 1992. 6. Muss HB, Case LD, Richards F. Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. N Engl J Med 325: 1342-1348, 1991. 7. Olson R, Boerth R, Gerber J, et al. Minireview: mechanism of adriamycin cardiotoxicity: Evidence for oxidative stress. Life Sci 29: 1393-1401, 1982. 8. Marshall E. Breast cancer: stalemate in the war on cancer. Science 254: 1719-1720, 1991. 9. Ingram B. Cancer strides challenged: establishment’s therapeutic claims overstated, says activist coalition. Medical Tribune 33: 1,1992. 10. Stepp W, Kuhnau D, Schroeder H. The vitamins and their clinical applications. The Vitamin Products, Co., Milwaukee, WI, pg. xiii, 1938. 11.Toufexis A. The new scoop on vitamins. Time 139 (14): 54-59, 1992. 12. Slutsker L, Hoesly F, Miller L, et al. Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer. JAMA 264: 213-217, 1990. 13. Sakimoto K. The cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med 323: 992-993, 1990. 14. Mayeno A, Lin F, Foote C, et al. Characterization of "Peak E", a novel amino acid associated with eosinophilia myalgia syndrome. Science 250: 1707-1708, 1990. 15. Raphals P. Disease puzzle nears solution. Science 249: 619, 1990. 16. Belongia E, Hedberg C, Gleich G, et al. An investigation of the cause of the eosinophilia myalgia syndrome associated with tryptophan use. N Engl J Med 323: 357-365, 1990. 17. Henley EC. Food and Drug Administration’s proposed labeling rules for protein. J Am Dietetics Assoc 92: 293-296, 1992. 18. Psczcola, DE. The nutraceutical initiative: a proposal for economic and regulatory reform. Food Tech (April): 77-79, 1992. 19. Herbert V. L-Tryptophan. A medicolegal case against over-the-counter marketing of supplements of amino acids. Nutr Today (March/April): 27-30, 1992. 20. Stare F. Some more comments on Silent Spring. Nutr Rev 50: 61-62, 1992. TABLE 1 The RDAs And RDIs Of Selected Nutrients Nutrient 1989 RDA* Proposed “Reference Daily Intake” (RDI) Percent Decrease Vitamin A 1000 RE** 875 RE 12 Vitamin D 10 mcg 6.5 mcg 35 Vitamin E 10 aTE*** 9 aTE 10 Vitamin B6 2 mg 1.5 mg 25 Biotin 100 mcg 60 mcg 40 Magnesium 400 mg 300 mg 25 Phosphorus 1200 mg 900 mg 25 * Highest 1989 RDA. ** Retinol equivalents. ***a-Tocopherol equivalents. Nutrition: At The Crossroads Brian Leibovitz, Ph.D.
Editorial JON 2(4), 1993 Brian Leibovitz, Ph.D.The focus of JON is on optimizing the quantity of dietary macronutrients (carbohydrates, lipids, proteins) and micronutrients (vitamins, minerals, non-vitamin nutrients, and other food factors) for the prevention and/or treatment of disease and for the maintenance of optimal health. A tremendous volume of data now exist that clearly document the pivotal role of nutrition in the management of most human ailments. The sheer magnitude of the scientific literature supporting this concept makes it difficult for even the most close- minded individuals (e.g., Victor Herbert, Stephen Barrett, or Frederick Stare) or agencies (e.g., FDA, FASEB, or CSPI) to deny the medical benefits of supplementary nutrients.
The primary challenge facing nutritionists today is elucidation of optimal levels of nutrients in the diet and in the body. JON is the first journal specifically dedicated to solving this question.
Nutrition is nothing less than the foundation of medicine, the cornerstone of all medical therapeutics. Despite the overwhelming evidence showing the clinical benefits, we are still faced with an extremely complex and (at present) almost incomprehensible problem: what are the optimal nutrient intakes — particularly for micronutrients? Because nutritionists have focused on dietary deficiencies, no one really knows how much of a given nutrient is optimal. But at least we are now asking the right questions.
This is a special issue on "Nutrition And Health" -- a Forum in which the Editorial Board Members have been invited to relate their perspective of how nutrition relates to health and disease. Because of the many significant contributions by JON's Board Members in a vast array of subjects, their opinions and viewpoints on future developments in nutrition should be of interest to JON readers and to the nutritional community at large.
All JON Board Members were invited to submit a short, succinct article which reflects their vision of the role of nutrition in health. Due to the special nature of this Forum, I asked that references be used sparingly. As with the previous Forum ["The Future Of Nutrition", JON 1(1), 1992], articles in this issue have not undergone the peer-review process.
This Forum is essentially a format to promote novel ways of looking at the ever-expanding field of nutrition. The goal is to provide new, creative concepts, as well as important findings, from those who are at the cutting edge of nutrition. The ideas and concepts generated by this Forum have the potential to significantly influence nutritional research - at the very least by stimulating the thought process of the next generation of nutritionists. It is with great pleasure that I invite you to spend a few moments and enjoy the reflections and insights of many of the world's leading nutritionists -- individuals who have devoted their lives to the study of the most basic, yet applicable, field of medical science.
JON 2(4), 1993