"Progress in Megavitamin and Orthomolecular Science" (pages 1-25) (June 12, 1984)
"Progress in Megavitamin and Orthomolecular Science" (pages 26-48) (June 12, 1984)
Progress in Megavitamin and Orthomolecular Science
During the first half of the 20th Century the several fat-soluble and water-soluble vitamins were identified, isolated, and
characterized and methods for their synthesis were developed. By 1943 the Recommended Dietary Allowances (RDAs)
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were formulated and published by the Food and Nutrition Board of the U.S. National Academy of Sciences -- National Research
Council, which has revised its recommendations about every five years! The RDAs are defined in the following way^1: "Recommended
Dietary Allowances (RDA) are the levels of intake of essential nutrients
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considered, in the judgment of the Committee on Dietary Allowances of the Food and Nutrition Board on the basis of available
scientific knowledge, to be adequate to meet the known nutritional needs of practically all health persons."
The Board states that the RDAs are intended to be met by a [ . . . ] of a wide variety of foods rather than
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by supplementation or by extensive fortification of single foods, and that they apply to healthy populations, not to those
people with problems such as premature birth, inherited metabolic disorders, infections, chronic diseases, and the use of
medications requiring special dietary and therapeutic measures.
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During the second half of the 20th century it has been recognized that there is a fallacy in the definition of the RDAs.
The fallacy lies in the last words of the definition, " . . . to meet the known nutritional needs of practically all healthy
persons." Thus the "nutritional needs" are the amounts ingested by the control
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subpopulation of people in "ordinary good health." Since the nutrient intake of these people is an average one, the
definition of RDA leads to values of the RDA equal to the amounts in the average diet.
With this definition, there is no possibility that the RDAs would be given values that would improve the health of all the
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This fallacy is well known, even though the U.S. Food and Nutrition Board does not tell the American people about it. In
their book Human Nutrition and Dietetics^2 the authors, Sir Stanley Davidson and R. Passmore, mention that the different recommendations
of the national committees of Britain and the USA are related to the customary diets of the two countries [p. 242]. They
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also say [p. 213] that the chief argument against recommending an intake of vitamin C that would lead to full saturation and
improve the general health is that it would require a revolution in British habits to eat sufficient fruit and vegetables
to provide the vitamin in this amount.
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The value of megavitamins
The recognition of the value of an intake of a vitamin larger than the intake that prevents manifestations of the corresponding
deficiency disease has come mainly during the second half of the 20th century. In 1937 Albert Szent-Gyorgyi wrote^3 that
"Vitamins, if properly understood and applied, will help us to reduce human suffering to
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an extent which the most fantastic mind would find to imagine." In the period from 1940 on values of intake of vitamins
somewhat larger than the RDAs were tested for prophylactic and therapeutic value. The early investigators were conservative;
for example, Cowan, Diehl, and Baker, who in 1942 reported that
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in their double-blind study of 363 students who received vitamin C or a placebo, with 31% less respiratory illness in the
vitamin C group than in the placebo group, described the daily dose of 200 mg (four times the RDA) as a "massive"
dose. A dose of 27,000[?] mg is now considered a massive dose.
Megavitamin therapy was developed in 1952
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by A. Hoffer and H. Osmond, in Saskatoon, Saskatchewan, who then began the first double-blind study ever made in the field
of psychiatry. In this study of 30 schizophrenic patients a comparison was made of a placebo, nicotinic acid, and nicotinamide
(each as an adjunct to standard schizophrenia treatment. The patients receiving vitamin
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B3 (nicotinic acid or nicotinamide) fared better than those given a placebo: Hoffer states [Ref 4, p. 207] "A second
double-blind study with 82 patients, follow-up studies since 1952, and clinical experience on nearly 2,000 cases treated between
1952 and 1969 have clearly established for me that the treatment of choice for schizophrenia is a
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combination of megavitamins, tranquilizers, anti-depressants, and electroconvulsive therapy, combined with psychotherapy within
the framework of the medical model. An example of independent corroboration is the work of Hawkins (Ref. 4, pp. 571-673).
He and his clinic have treated over 4,000 cases, and the vast majority were restored to normality."
This more recent work may
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considered to be the logical consequence of earlier studies by many investigators of the value of this vitamin, which had
been recognized in 1933 to the pellagra-preventing vitamin, in controlling the psychosis associated with pellagra and also
in controlling depression and other psychotic states. The
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early studies are described by Hoffer (Ref. 4, pp. 203-205). The RDA of vitamin B3 is 17 mg per day. In the early studies
daily amounts from 100 mg to 1000 mg per day were used. Hoffer and Osmond, Hawkins, and other psychiatrists prescribe 3,000
or more mg per day, usually together with an equal amount of ascorbic acid and often with other vitamins.
The biological importance
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of vitamin B3 results from its involvement with enzymes in nicotinamide is a constituent of nicotinamide-adenine dinucleotide
(NAD) and nicotinamide-adenine dinucleotide phosphate (NADP), which serve as coenzymes in may enzyme systems.
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Another early investigator in the megavitamin field was Fred R. Klenner. Following the 1935 report by Jungeblut of the inactivation
of poliomyelitis virus by ascorbate ion^5 , Klenner before 1949 began the treatment of patients seriously ill with viral pneumonia,
poliomyelitis, and other viral diseases by oral administration or venous infusion of ascorbate, often
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in amounts so large as 100 g per day^(6-10). He recommended 10 to 20 g per day for prophylaxis. The biochemist Irwin Stone
also played an important part in this development by marshalling the arguments about the optimum intake of vitamin C and advocating
the prophylactic and therapeutic use in amounts far larger than the RDA^(11,12).
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Orthomolecular Substances and Orthomolecular Medicine
Most drugs have little physiological activity at doses far less than those at which they show pronounced activity, and the
doses of drugs usually prescribed for the treatment of a serious illness are usually rather close to the lethal dose. In
these respects the vitamins are much different. A daily intake
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of 5 mg of nicotamide [sic] is enough to prevent pellagra from developing in most people, but 50g, 10,000 times as much, can
be taken without harm. Similarly, 5 mg of ascorbic acid per day is enough to prevent scurvy in most people, but 10,000 or
even 50,000 times this amount can be taken without harm. No lethal does is known for these vitamins or for
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most of the others -- it is estimated that a single dose of 10,000,000 I.U. of vitamin A might be lethal.
Because the vitamins and some other substances have physiological activity over a great range of tolerated intakes, and important
question may be asked: What is the optimum intake?
For a vitamin the optimum intake may be
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far greater than the RDA. Only during recent decades has there been serious interest in determining the optimum intakes.
In order to differentiate them from drugs, the vitamins and similar substances have been given the name orthomolecular substances^13.
An orthomolecular substance is a substance that is normally present in the
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human body and that serves some purpose. The vitamins, essential amino acids, essential fats, essential minerals, and various
other constituents of foods are orthomolecular substances, as are also various other substances, such as choline, p-aminobenzoic
acid, the ubiquinones, and human proteins such as insulin and interferon.
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Orthomolecular medicine is the achievement and preservation of the best of health and the prevention and treatment of disease
by varying the concentrations of the orthomolecular substances in the human body. Reaching the goal may involve either increasing
the concentration (of, for example, high-density lipoprotein in the blood) or decreasing the concentration (of, for example,
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Optimum intakes of vitamins
During recent years the effort has been made to estimate the optimum intakes of vitamins. The curve expressing wellbeing
as a function of the intake of a vitamin is expected to have a rather flat top, and the optimum intake depends on the genetic
constitution of the person and on the state of his health. For a person in ordinary
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health the optimum intake of vitamin C may be 100 or 200 times the RDA, that for the B vitamins and vitamin E about 25 times
the RDA, and that for vitamin A about 10 times the RDA. Evidence supporting the high values of the optimum intake of vitamin
C is discussed by Stone^12 and by Pauling^(3,14).
The idea that the amounts of vitamins provided by an
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ordinary food diet are adequate seems to be based on two arguments. One is that people on a poor diet show manifestations
of deficiency diseases that disappear when the diet is improved. The fallacy in this argument is that the health of the control
population, receiving a good diet, may be improved further by increased intakes of the
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vitamins; that is, the intakes provided by an ordinary good diet are adequate for ordinary health but not for the best of
health. The other argument is that the plants that are the source of the vitamin-containing foods are similar in their biochemistry
to human beings, and that accordingly the amounts of vitamins
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that they manufacture, which are adequate for them, are also adequate for human beings. One of the fallacies in this argument
is that human beings require vitamin C for the synthesis of the principal structural macromolecule of the human body, the
protein collagen, whereas plants use a carbohydrate, cellulose, as their principal structural
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macromolecule, and hence have a smaller need for vitamin C. Another fallacy^(13,15) is that an organism that synthesizes
a vital substance synthesizes a somewhat smaller daily amount than the optimum, because to synthesize the optimum amount would
require supporting the burden of additional synthetic
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machinery, with only a smaller compensation.
The Food and Nutrition Board recognizes that the RDAs do not apply to persons with vitamin-related genetic diseases. More
than 100 of these diseases are known, most them with strikingly serious manifestations. It is estimated that many thousands
of less serious vitamin-related abnormalities occur, with nearly every person bearing one or more. The
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biochemical individuality discussed by Roger J. Williams^(15,16,17) may arise mainly in this way. Much of the improvement
in health resulting from optimum nutrition may result from control of minor genetic defects.
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Vitamin B/b and the carpel tunnel syndrome
Either a low intake of vitamin B/b (pyridoxine, pyridoxal, pyridoxamine) or the administration of an antagonist (deoxypriadoxine)
leads to serious problems -- convulsions, depression and confusion, dermatitis, stomatitis, and cheilosis. Pyridoxal phosphate
and pyridoxamine are coenzymes for many enzymes including those of amino-acid metabolism, and the
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effects of deprivation are attributed to the decreased functioning of the enzymes. The fact that ordinary health is restored
by administration of pyridoxine in amounts not much greater than the RDA (2.2 mg/per day for an adult male) has given rise
to the belief that the various enzyme synthesis dependent on B-b function at nearly their maximum level in persons receiving
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RDA intake of the vitamin. Recent work by John M. Ellis, Karl Folkers and their collaborators has shown that this conclusion
is not justified. In his practice in a small Texas community Ellis discovered that an increased intake to pyridoxine helped
to control rheumatism, edematous conditions, carpal tunnel syndrome, menopausal arthritis, clinical disturbances following
the use of
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antiovulatory pills, and some other problems^(18,19). The doses used were usually between 50 and 300 mg per day. He and
Folkers, co-author of a treatise on vitamins^20, found that many subjects with the ordinary intake of B6 has an activity of
the B6-dependent enzyme EGOT (erythrocyte glutamic oxaloacetic transferase) far lower than that achieved with a high
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B6 intake. It was shown in a double-blind controlled-trial with patients with carpal tunnel syndrome that the administration
of 100 mg of pyridoxine per day, about 50 times the RDA, led to control of the disease, whereas administration of a [ . .
. ] did not^21. The mechanism of action may involve the shrinking of the synovial membranes adjacent to the nerve. The authors
conclude that clinical
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improvement of the syndrome with pyridoxine therapy may frequently eliminate hand surgery, and mention that carpal tunnel
syndrome is often associated with rheumatoid arthritis, obesity, myxedema, diabetes, pregnancy, and rheumatoid conditions
such as "tennis elbow," Dupuytren contracture, denervain[?] disease, "trigger fingers," bursitis, and periarthritis
of the shoulder.
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These conditions are so common as to suggest that nearly everyone would benefit by the orthomolecular intake of this vitamin.
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Vitamin C and Cancer
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Vitamin and cardio-vascular disease
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1. Committee on Dietary Allowances, Food and Nutrition Board, Recommended Dietary Allowances, National Academy of Sciences,
Washington, D.C.. Ninth edition, 1980.
2. S. Davidson and R. Passmone, Human Nutrition and Dietetics, Williams and Wilkins Co., Baltimore, Md., 4th edn, 1970.
3. Quoted in L. Pauling, Vitamin C, the Common Cold, and the Flu, W.H. Freeman and Co., San Francisco, 1976.
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4. D. Hawkins and L. Pauling, eds., Orthomolecular Psychiatry: Treatment of Schizophrenia, W.H. Freeman and Co., San Francisco,
5. C.W. Jungeblut, J. Exper. Med. 62, 517-521 (1935).
6. F.R. Klenner, J. Southern Med. and Surg. 110, 60-63 (1948)
7. F.R. Klenner, J. Southern Med. and Surg. 111, 210-214 (1949).
8. F.R. Klenner, J. Southern Med. and Surg. 113, 107-107 (1951).