On the Orthomolecular Environment of the Mind: Orthomolecular Theory

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On the Orthomolecular Environment of the Mind: Orthomolecular Theory

 

" Varying the concentrations of substances normally present in the human body may

control mental disease. " - Linus Pauling

 

 

" The methods principally used now for treating patients with mental disease are

psychotherapy (psychoanalysis and related efforts to provide insight and to

decrease environmental stress), chemotherapy (mainly with the use of powerful

synthetic drugs, such as chlorpromazine, or powerful natural products from

plants, such as reserpine), and convulsive shock therapy (electroconvulsive

therapy, insulin coma therapy, pentylenetetrazol shock therapy). I have reached

the conclusion that another general method of treatment, which may be called

orthomolecular therapy, may be found to be of great value, and may turn out to

be the best method of treatment for many patients. " - Linus Pauling, Science,

April 19, 1968, p. 265

 

The author defines orthomolecular psychiatry as the achievement and preservation

of good mental health by the provision of the optimum molecular environment for

the mind, especially the optimum concentrations of substances normally present

in the human body, such as the vitamins. He states that there is sound evidence

for the theory that increased intake of such vitamins as ascorbic acid, niacin

pyridoxine, and cyanocobalamin is useful in treating schizophrenia. The negative

conclusions of APA Task Force Report 7, Megavitamin and Orthomolecular Therapy

in Psychiatry, he says, result not only from faulty arguments and from a bias

against megavitamin therapy but also from a failure to deal fully with

orthomolecular therapy in psychiatry- Three psychiatrists comment on Dr.

Pauling's presentation.

 

 

Orthomolecular psychiatry is the achievement and preservation of mental health

by varying the concentrations in the human body of substances that are normally

present, such as the vitamins- It is part of a broader subject, orthomolecular

medicine, an important put because the functioning of the brain is probably more

sensitively dependent on its molecular composition and structure than is the

functioning of other organs (1) . After having worked for a decade on the

hereditary hemolytic anemias, I decided in 1954 to work on the molecular basis

of mental disease. I read the papers and books dealing with megavitamin therapy

of schizophrenia by Hoffer and Osmond (2,4) as well as the reports on studies of

vitamins in relation to mental disease by Cleckley and Sydenstricker (5,6) and

others. In the course of time I formulated a general theory of the dependence of

function on molecular structure of the brain and other parts of the body and

coined the adjective " orthomolecular " to describe it (1).

 

There is no doubt that the mind is affected by its molecular environment. The

presence in the brain of molecules of LSD, mescaline, or some other

schizophrenogenic substance is associated with profound psychic effects. Mental

manifestations of avitaminosis have been reported for several vitamins. A

correlation of behavior of school children with concentration of ascorbic acid

in the blood (increase in " alertness " or " sharpness " with increase in

concentration) has been reported by Kubala and Katz (7). A striking abnormality

in the urinary excretion of ascorbic acid after an oral loading dose was

reported for chronic schizophrenics by VanderKamp (8) and by Herjanic and

Moss-Herjanic (9). My associates and I (10) carried out loading tests for three

vitamins on schizophrenic patients who had recently been hospitalized and an

control subjects. The percentage of schizophrenic patients who showed low

urinary excretion of each vitamin was about twice as great as that of the

controls: for ascorbic acid, 74 percent of the schizophrenic patients showed low

urinary excretion versus 32 percent of the controls; for niacinamide, 81 percent

versus 46 percent; and for pyridoxine, 52 percent versus 24 Percent. The

possibility that the low values in urinary excretion of thew vitamins for

schizophrenic patients resulted from poor nutrition is made unlikely by the

observation that the numbers of subjects low in one, two, or all three vitamins

corresponded well with the numbers calculated for independent incidence.

 

There are a number of plausible mechanisms by which the concentration of a

vitamin may affect the functioning of the brain. One mechanism, effective COT

vitamins that serve as coenzymes, is that of shifting the equilibrium for the

reaction of apoenzyme and coenzyme to give the active enzyme. An example is the

effectiveness of cyanocobalamin (vitamin B12) given in amounts 1,000 times

greater than normal to control the disease methylmalonic aciduria (11-14). About

half of the patients with this disease are successfully treated with megadoses

of vitamin B12 . In these patients a genetic mutation has occurred and an

altered apoenzyme that has a greatly reduced affinity for the coenzyme has been

produced. Increase in concentration of the coenzyme can counteract the effect of

the decrease in the value of the combining constant and lead to the formation of

enough of the active enzyme to catalyze effectively the reaction of conversion

of methylmalonic acid to succinic acid.

 

In the human population there may be several alleles of the gene controlling the

manufacture of each apoenzyme; in consequence the concentration of coenzyme

needed to produce the amount of active enzyme required for optimum health may

well be somewhat different for different individuals- In particular, many

individuals may require a considerably higher concentration of one Or more

coenzymes than other people do for optimum health, especially for optimum mental

health. It is difficult to obtain experimental evidence for gene mutations that

lead to only small changes in the properties of enzymes. The fact that genes

that lead to large and more easily detectable changes in the properties of

enzymes occur, as in individuals with methylmalonic aciduria, for example,

suggests that mutations that lead to small changes also occur.

 

Significant differences in enzyme activity in different individuals have been

reported by many investigators, especially by Williams [15], who has made many

studies of biochemical individuality. It is likely that thorough studies of

enzymes would show them to be similar to the human hemoglobins. A few of the

abnormal human hemoglobins, most of which involve only the substitution of one

amino-acid residue for another in either the alpha chain or the beta chain of

the molecule, differ greatly in properties from normal adult hemoglobin, leading

to serious manifestations of disease.

 

It was in the course of the study of one of these diseases, sickle cell anemia,

that the first abnormal hemoglobin was discovered (16). Most of the abnormal

human hemoglobins, however. differ from normal hemoglobin in their properties to

only a small extent, so that there is no overt manifestation of diseaseThere is,

nevertheless, the possibility that even the small changes in properties of an

abnormal hemoglobin associated with a mild hemoglobinopathy will have

deleterious consequences. An example is the intolerance to sulfa drugs

associated with the substitution of arginine for histidine in the locus 58 in

the alpha chain or 63 in the beta chain. It is likely that individual

differences in enzyme activity will in the course of time be shown to be the

result of differences in the amino-acid sequences of the polypeptide chains of

the apoenzymes.

 

More than 100 abnormal human hemoglobins are now known, and the human population

may be expected to be similarly complex with respect to many enzymes, including

those involved in the functioning of the brain. A tendency to schizophrenia is

probably polygenic in origin. I have suggested (1) that the genes primarily

involved in this tendency may well be those which regulate the metabolism of

vital substances such as the vitamins.

 

Some vitamins are known to serve as coenzymes for several enzyme systems. We

might ask if the high concentration of coenzyme required to produce the optimum

amount of one active enzyme might not lead to the production of far too great an

amount of another active enzyme. The answer to this question is that the danger

is not very great. For most enzymes the concentration of coenzyme and the value

of the combination constant are such that most (90 percent or more) of the

protein is converted to active enzyme. Accordingly, a great increase in

concentration would increase the amount of most active enzymes by only a few

percentage points, whereas it might cause a great increase for a mutated enzyme.

 

The Orthomolecular Treatment of Schizophrenia

In the book Orthomolecular Psychiatry: Treatment Of Schizophrenia (17) my

colleagues and I pointed out that the orthomolecular treatment of schizophrenia

involves the use of vitamins (megavitamin therapy) and minerals; the control of

diet, especially the intake of sucrose; and, during the initial acute phase, the

use of conventional methods of controlling the crisis, such as the

phenothiazines. The phenothiazines are not, of course, normally present in the

human body and are not orthomolecular. However, they are so valuable in

controlling the crisis that their use is justified in spite of their undesirable

side effects.

 

Hawkins (18) stated that his initial combination of vitamins for the treatment

of schizophrenia was I gin. of ascorbic acid, I gm, of niacinamide, 50 mg. of

pyridoxine, and 400 I.U. of vitamin E four times a day. Other vitamins may also

be given. A larger intake, especially of niacinamide or niacin may be

prescribed; the usual amount seems to be about 8 gm. a day after an initial

period on 4 gm. a day.

 

The vitamins, as nutrients or medicaments, pose an interesting question. The

question is not, Do we need them? We know that we do need them, in small

amounts, to stay alive. The Teal question is, What daily amounts of the various

vitamins will lead to the best of health, both physical and mental? This

question has been largely ignored by medical and nutritional authorities.

 

Let us consider schizophrenia, Osmond (19) stated that about 40 percent of

schizophrenics hospitalized for the first time are treated successfully by

conventional methods in that they are released and not hospitalized a second

time. The conventional treatment fails for about 60 percent in that the patient

is not released or is hospitalized again. Conventional treatment includes a

decision about vitamin intake. Usually it is decided that the vitamins in the

food will suffice or that a multivitamin tablet will also be given. The amounts

of ascorbic acid, niacin pyridoxine, and vitamin E may be approximately the

daily allowances recommended by the Food and Nutrition Board of the U.S.

National Academy of Sciences-National Research Council: 60 mg. of ascorbic acid,

20 mg of niacin 2 mg. of pyridoxine, and 15 I.U. of vitamin E. Is this amount of

vitamins correct? Would many schizophrenic patients respond to their treatment

better if the decision were made that they should receive 10 or 100 or 500 times

as much of some vitamins? What is the optimum intake for these patients? I

believe there is much evidence that the optimum intake for schizophrenic

patients is much larger than the recommended daily allowances. By the use of

orthomolecular methods in addition to the conventional treatment of

schizophrenia, the fraction of patients hospitalized for the first time in whom

the disease is controlled may be increased from about 40 percent to about 80

percent. (19)

 

Ascorbic Acid

It was reported by Horwitt in 1942 (20) and by later investigators that

schizophrenic patients receiving the usual dietary amounts of ascorbic acid had

lower concentrations of ascorbic acid in the blood than people in good health.

The loading-test results of VanderKamp (8), Herjanic and Moss-Herjanic (9), and

Pauling and associates (10) have been mentioned above. In his discussion of

ascorbic acid and schizophrenia Herjanic (21) concluded:

 

The individual variation of the need for ascorbic acid may turn out to be one of

the contributing factors in the development of the illness. Ascorbic acid is an

important substance necessary for optimum functioning of many organs. If we

desire, in the treatment of mental illness, to provide the " optimum molecular

environment, " especially the optimum concentration of substances normally

present in the human body (Pauling,. 1968 (1)), ascorbic acid should certainly

be included (2).

 

There is, moreover, a special reason for an increased intake of ascorbic acid by

patients with schizophrenia or any other disease for which there is only partial

control. About 60 mg. of ascorbic acid a day is enough to prevent overt

manifestations of avitaminosis C (scurvy) in most people. However, there are

several significant arguments to support the thesis that the optimum intake for

most people is 10 to 100 times more than 60 mg. These arguments are summarized

in the papers and books of Irwin Stone (22) and myself (23,24). They constitute

the theoretical basis for the customary use of about 4 gin. of ascorbic acid a

day in the orthomolecular therapeutic and prophylactic treatment of

schizophrenia. A significant controlled trial of ascorbic acid in chronic

psychiatric patients was reported in 1963 by Milner (25). The study, which was

double-blind, was made with 40 chronic male patients: 34 had schizophrenia, 4

had manic-depressive psychosis, and 2 had general paresis. Twenty of the

patients, selected at random, received 1 gm. of ascorbic acid a day for three

weeks; the rest received a placebo. The patients were checked with the Minnesota

Multiphasic Personality Inventory (MMPI) and the Wittenborn Psychiatric Rating

Scales (WPRS) before and after the trial. Milner concluded that " statistically

significant improvement in the depressive, manic, and paranoid

symptoms-complexes, together with an improvement in overall personality

functioning, was obtained following saturation with ascorbic acid " (25). He

suggested that chronic psychiatric patients would benefit from the

administration of ascorbic acid.

 

We found (10) that of 106 of the schizophrenic patients we studied who had

recently been hospitalized in a private hospital, a county-university hospital,

or a state hospital, 81 (76 percent) were deficient in ascorbic acid, as shown

by the six-hour excretion of less than 17 percent of an orally administered

close. Only 27 of 89 control subjects (30 percent) showed this deficiency. Great

deficiency (less than 4 percent excreted) was shown by 24 (22 percent) of the

schizophrenic subjects and by only 1 (1 percent) of the controls. I have no

doubt that many schizophrenic patients would benefit from an increased intake of

ascorbic acid. My estimate is that 4 gm. of ascorbic acid a day, in addition to

the conventional treatment, would increase the fraction of acute schizophrenics

in whom the disease is permanently controlled by about 25 percent, Except for

that of Milner (25), no controlled trial of ascorbic acid in relation to

schizophrenia has been made, so far as I know.

 

Niacin and Niacinamide

The requirement of niacin (nicotinic acid) for proper functioning of the brain

is well known. The psychosis of pellagra, as well as the other manifestations of

this deficiency disease, is prevented by the intake of a small amount of niacin,

about 20 mg. a day. In 1939 Cleckley, Sydenstricker, and Geeslin (5) reported

the successful treatment of 19 patients with severe psychiatric symptoms with

niacin and in 1941 Sydenstricker and Cleckley (6) reported similarly successful

treatment of 29 patients with niacin. In both studies, moderately large doses of

niacin, 0.3 to 1.5 gm. a day, were given. None of the patients in these studies

had physical symptoms of pellagra or any other avitammosis. A decade later,

Hoffer and Osmond (2,3) initiated two doubleblind studies of niacin or

niacinamide in the treatment of schizophrenia. Another double-blind study was

reported by Denson in 1962 (26). In 1964 Hoffer and Osmond (4) reported that a

10-year follow-up evaluation of the patients in their initial studies showed

that 75 percent had not required hospitalization, compared with 36 percent of

the comparison group, who had not received niacin. Similar estimates have been

made by Hawkins (18). There are, however, contradictory statements by other

investigators. The question of the weight of the evidence is discussed below in

the section on the APA task force report.

 

Pyridoxine

Pyridoxine, vitamin B6 is used in the treatment of schizophrenia in amounts of

200 to 800 mg. a day by many orthomolecular psychiatrists, Derivatives of this

vitamin are known to be the coenzymes for over 50 enzymes, and the chance of a

genotype with need for a large intake of the vitamin is accordingly great. There

is evidence that pyridoxine is involved in tryptophan-niacin metabolism.

A double-blind placebo-controlled study has been made of pyridoxine and niacin

by Ananth, Ban, and Lehmann (27). Their experimental population consisted of 30

schizophrenic patients: 15 were men, 15 were women, their mean age was 41.7

years, and their mean duration of hospitalization was 10.9 years. They were

randomly assigned to three treatment groups: 1) the combined treatment group,

which received 3 gm. of nicotinic acid a day for 48 weeks and 75 mg. of

pyridoxine a day during three 4-week periods; 2) the nicotinic acid group, which

received 3 gm. of nicotinic acid a day for 48 weeks and a pyridoxine placebo;

and 3) the pyridoxine group, which received 75 mg- of pyridoxine a day during

three 4 week periods and a nicotinic acid placebo. In addition, neuroleptic

preparations were administered according to clinical requirements for the

control of psychopathology. The investigators reported that " of the ten patients

in each treatment group, seven improved and three deteriorated in the nicotinic

acid group, nine improved and one deteriorated in both the combined treatment

group and in the pyridoxine group " (27). They also stated:

 

Of the three indices of therapeutic effects, global improvement in

psychopathology (Brief Psychiatric Rating Scale and Nurses Observation Scale for

Inpatient -Evaluation) scores was seen in all three groups: the number of days

of hospitalization during the period of the clinical study was lower in both the

nicotinic acid and the combined treatment group; and only in the combined

treatment group was the daffy average dosage of phenothiazine medication

decreased. Thus, improvement in all three indices was noted in the combined

treatment group. However, several side effects were observed during the

therapeutic trials, indicating that the vitamins used are not completely safe

(27).

 

 

The investigators reached the conclusion that " on balance, these results suggest

that the addition of pyridoxine may potentiate the action of nicotinic acid.

Thus pyridoxine seems to be a useful adjunct to nicotinic acid therapy " (27).

Hawkins (18) commented on this work in the following way:

 

The therapeutic effect was demonstrable even though the patients had been

hospitalized for an average of 10.9 years, were not on hypoglycemic diets, and

the doses of both pyridoxine (75 mg. daily) and vitamin B3 (3 gm. a day) were

considerably below the dosages we routinely prescribe (18).

 

Cyanocobalamin

A deficiency in cyanocobalamin (vitamin B12), whatever its cause, leads to

mental illness as well as to such physical manifestations as anemia. The anemia

can be controlled by a large intake of folic acid, but the mental illness and

neurological damage cannot. A pathologically low concentration of cyanocobalamin

in the blood serum has been reported to occur in a much larger percentage of

patients with mental illness than in the general population. Edwin and

associates (28) determined the amount of vitamin B12 in the serum of every

patient over 30 years old admitted to a mental hospital in Norway during a

period of one year. Of the 396 patients, 61 (15-4 percent) had a subnormal or

pathologically low concentration of vitamin B 12, less than 150 pg. per ml. (the

normal range is 150 to 1,300 pg. per ml.). This incidence is 30 times as great

as that estimated for the population as a whole. Other investigators have

reported similar results and have suggested that a low serum concentration of

vitamin B12, whatever its origin, may cause mental illness. In addition, of

course, mental illness may accompany some genetic diseases, such as

methylmalonic aciduria, which can be controlled only by achieving a serum

concentration of cyanocobalamin far greater than normal.

 

Minerals and Other Vitamins

There is some evidence that mental illness may result from deprivation of or

abnormal need for minerals and other vitamins. (See, for example, Pfeiffer,

Iliev, and Goldstein (29)). Further work in this field by psychiatrists and

biochemists is needed.

 

The APA Task Force Report

In July 1973 an APA task force of five physicians and one consultant issued a

54-page report titled Megavitamin and Orthomolecular Therapy in Psychiatry (30).

In this report the Task Force on Vitamin Therapy in Psychiatry purports to

present both theoretical and empirical reasons for completely rejecting the

basic concept of orthomolecular psychiatry, which is the achievement and

preservation of good mental health by the provision of the optimum molecular

environment for the mind, especially the optimum concentrations of substances

normally present in the human body.

 

Some Errors in the Report

It is mentioned in the report that in the treatment program of the

orthomolecular psychiatrists " each patient may receive as many as six vitamins

in large doses individually determined by the treating physician as well as

other psychotropic drugs and hormones whose doses are also individually

determined for each patient " (p. 46). The assumption is made by the task force

that the optimum intake of vitamins for mental health is the conventional

average daily nutritional requirement, with growth and development as the

criteria: " In schizophrenia there is apparently an adequate vitamin intake for

growth and development until the illness becomes manifest in the teens or early

adult life " (p. 40). Mention is made in the report of the well-known genetic

diseases with both psychic and somatic manifestations that can be controlled by

an intake of a vitamin 100 or 1,000 times the usually recommended daily

allowance, but the possibility that less obvious genetic differences could

result in an increased individual need for a larger intake of vitamins in order

to achieve good mental health, as discussed in my 1968 publication (1) and in

the earlier sections of this paper, is rejected on the basis of arguments that

have little value or pertinence. One such argument is the following:

 

The two theoretical bases adduced by megavitamin proponents for the

effectiveness of NA therapy (nicotinic acid as a methyl acceptor and NAD

deficiency) are in fact generally incompatible, because NAA [nicotinamide], when

functioning as a vitamin, is bound to the remainder of the coenzyme molecule by

the nitrogen of its pyridine ring and hence can no longer accept methyl groups.

Essentially, then, the two views of NA as a vitamin precursor of NAD and as a

methyl acceptor are incompatible, except for the possibility that there is in

schizophrenia double deficit - both a vitamin deficiency and a transmethylation

defect and that nicotinic acid has the happy fortune to serve two purposes

simultaneously (pp. 40-42).

 

There is an obvious error in this task force argument. There is no

incompatibility between two functions of nicotinic acid; some molecules may

engage in one function and others in the other. A defect in either function

might be controlled by increasing the intake of the vital substance. A " double

deficit " is not needed. The authors of the report would have wen the fallacy in

their argument if they had set up some equilibrium and reaction rate equations,

as was done in my 1968 paper (1). The task force expresses an interesting

misunderstanding of the nature of vitamins, in the following words: " By common

definition a vitamin is not only an essential nutrient, but it is essential

because it is transformed into a coenzyme vital for metabolic reactions " (p.

41). In fact, this is not the common definition of a vitamin; it is wrong. Some

vitamins, including vitamin C, are not known to be transformed into a coenzyme.

This misunderstanding by the task force may have contributed to the

misinterpretation of the evidence for and the theoretical basis of

orthomolecular psychiatry.

Nicotinic acid as a methyl acceptor is referred to in the report: " From Study

No. 12: nicotinic acid in the dosage of 3000 mg. per day can neither prevent nor

counteract the psychopathology induced by the combined administration of a

monoamine oxidase inhibitor (tranylcypromine) and methionine " (p. 16). In fact,

the molecular weights of nicotinic acid and methionine (a methyl donor) are

nearly the same, 123 and 149, respectively. Instead of 3 gm., 16.5 gm. of

nicotinic acid would have had to be given each day to accept the methyl groups

donated by the 20 gm. of methionine that was given each day. The study referred

to as number 12 (31), which resulted in an exacerbation of the illness of 30

schizophrenic patients who participated in it, has no value as a test of the

methyl acceptor theory of nicotinic acid. Consideration of ethical principles

may have kept the investigators from repeating the study with use of the proper

equimolar amounts of nicotinic acid and methionine.

 

The Failure To Discuss Ascorbic Acid and Pyridoxine

In several places the APA task force report mentions the use of 1 to 30 gm. of

ascorbic acid a day by orthomolecular psychiatrists. There are, however, no

references to the literature. Milner's double-blind study (25) is not mentioned,

nor is there any discussion of the many papers in which a low level of ascorbic

acid in the blood of schizophrenics was reported. Neither the general theory of

orthomolecular psychiatry, as presented in my 1968 paper (1) nor any of the

special arguments about the value of ascorbic acid is presented or discussed in

any significant way. There is, moreover, no discussion in the report of

pyridoxine and no reference to the 1973 work by Ananth, Ban, and Lehmann (27) on

the potentiation by pyridoxine of the effectiveness of niacin in controlling

chronic schizophrenia. The title of the report, Megavitamin and Orthomolecular

Therapy in Psychiatry, is completely inappropriate, and the general condemnation

of megavitamin and orthomolecular therapy is unjustified.

 

Niacin

The report does my that it is possible that the other watersoluble vitamins will

prove to be more effective than niacin but it adds;

 

Nonetheless, the massive use of niacin has always been the cornerstone of the

theory and practice of megavitamin advocates. Since this has proved to have no

value when is it employed as the sole variable along with conventional

treatments of schizophrenia, the burden of proof for the complex and highly

individualized programs now advocated would appear to be on the proponents of

such treatment (p. 46).

 

I shall point out below that the principles of medical ethics prevent

orthomolecular psychiatrists from withholding from half of their patients a

treatment that they consider to be valuable. Controlled tests can be carried out

only by skeptics. I now ask whether the task force is justified in saying that

the massive use of niacin has been proved to have no value when it is employed

as the sole variable along with conventional treatments of schizophrenia. My

answer to this question, from a study of the evidence quoted in the report, is

that it is not justified. The evidence that niacin has no value is far from

conclusive. A beneficial effect of niacin or niacinamide was reported for three

double-blind studies (two by Hoffer and Osmond and their collaborators (2,3,32)

and one by Denson (26)) and in 12 open clinical trials by other investigators

referred to in the report. On the other hand, the report mentions 7 doubleblind

studies in which a statistically significant difference between the niacinamide

subjects and the controls was not observed.

A failure to reject with statistical significance the nun hypothesis that the

treatment and the placebo have equal value is not proof that the treatment has

no value. The explicit statistical analysis of an alternative hypothesis should

be carried out: for example, the hypothesis that there is a 10-percent or

20-percent greater improvement in the treated subjects than in the placebo

subjects. No such analysis has been published.

In fact, some of the " negative " studies indicate that the treatment has value.

The report states that " Greenbaum (33) reported a double-blind study of 57

schizophrenic children who received nicotinamide 1 gm. per 50 lbs of body weight

or placebo for six months. No statistically significant differences were seen in

the two groups as a result of the treatment " (P. 11). it is true that no

statistically significant differences were wen, but that is not the whole truth,

The principal criterion of improvement in this study was the increase in the

score on a clinical scale of observable behavior categories. The average

improvement in the score of the 17 children receiving niacinamide was 4.0 units

and that of the 24 controls was 2.6 units (there was a third group of 16

children who were given a tranquilizer and niacinamide). The children who were

given niacinamide showed a 54-percent greater improvement than the children who

were given placebo. The groups were too small, however, for the difference to be

significant at the 95-percent level of confidence. This study does not prove

that niacinamide has no value. Rather, it indicates that niacinamide has greater

value than the placebo, even though it fails to show this at the customary level

of statistical significance.

 

The Hoffer-Osmond Diagnostic Test

Two-thirds of the report relates to niacin and one-third to the Hoffer-Osmond

Diagnostic Test (HOD) (34), which has no special connection with megavitamin or

orthomolecular psychiatry except that it was devised by the originators of

niacin therapy. The report should have been given the- title Niacin Therapy and

the HOD Test, or published as two reports, one on niacin and one on the HOD

test. It would have been still better for the task force to have discussed

megavitamin and orthomolecular therapy in psychiatry fully.

 

The Question of Controlled Experiments

The report refers to the low credibility of the megavitamin proponents, whose

published results were not duplicated in studies carried out by one of the task

force members (p. 48). The penultimate sentence of the report is, " Their

credibility is further diminished by the consistent refusal over the past decade

to perform controlled experiments and to report their new results in a

scientifically acceptable fashion " (p. 48).

I have talked with the leading orthomolecular psychiatrists and have found that

they feel the principles of medical ethics prevent them from carrying out

controlled clinical tests, with half of their patients receiving orthomolecular

therapy in addition to the conventional treatment and the other half receiving

only the conventional treatment. It is the duty of the physician to give to

every one of his patients the treatment that in his best judgment will be of the

greatest value, Some psychiatrists, including Hoffer and Osmond, carried out

controlled trials 20 years ago. They became convinced that orthomolecular

therapy, along with conventional treatment, was beneficial to almost every

patient. From that time on their ethical principles have required that they give

this treatment and not withhold it from half of their patients. The task force

is wrong in criticizing the orthomolecular psychiatrists for not having carried

out controlled clinical trials during the last few years. Instead, it is the

critics, who doubt the value of orthomolecular methods, who are at fault in not

having carried out well-designed clinical tests.

It is also the duty of a physician to give to a patient a treatment that may

benefit him and is known not to be harmful. The incidences of toxicity and other

serious side effects of the doses of vitamins used in orthomolecular medicine

are low. There is significant evidence that an increased intake of certain

vitamins may benefit the patient. It is accordingly the duty of the psychiatrist

to prescribe these vitamins for him.

 

The Bias of the Task Force

The last sentence of the report reads as follows:

 

Under these circumstances this Task Force considers the massive publicity which

they promulgate via radio, the lay press and popular books, using catch phrases

which are really misnomers like " megavitamin therapy " and " orthomolecular

treatment, " to be deplorable (p. 48).

 

This sentence, like others in the report, shows the presumably unconscious bias

of the task force. " Promulgate " (misused here) is a pejorative word, and " catch

phrases " is a pejorative expression. I do not understand why megavitamin therapy

and orthomolecular treatment should be called misnomers. This concluding

sentence, like many others in the book, seems to me to have been written in

order to exert an unjustifiably unfavorable influence on the readers of the

report.

I have written two popular books, No More War! (35) and Vitamin C and the Common

Cold (24). I feel that each of them was worthwhile and that neither would have

been easily replaced by a more technical book. The second book (24) was written

because I had discovered in reading the medical literature that there was much

evidence there about the value of ascorbic acid in decreasing both the incidence

and the severity of the common cold and that this evidence had been suppressed

or misrepresented by the medical and nutritional authorities. Since publication

of the book, eight new studies have been reported. Every one of these has

verified the value of ascorbic acid. The APA report shows the same sort of

negative attitude as that shown by the authorities toward ascorbic acid in

relation to the common cold. There seems to be a sort of professional inertia

that hinders progress.

 

Conclusions

Orthomolecular psychiatry is the achievement and preservation of good mental

health by the provision of the optimum molecular environment for the mind,

especially the optimum concentrations of substances normally present in the

human body, such as the vitamins. There is evidence that an increased intake of

some vitamins, including ascorbic acid, niacin pyridoxine, and cyanocobalamin,

is useful in treating schizophrenia, and this treatment has a sound theoretical

basis. The APA task force report Megavitamin and Orthomolecular Therapy in

Psychiatry discusses vitamins in a very limited way (niacin only) and deals with

only one or two aspects of the theory. Its arguments are in part faulty and its

conclusions are unjustified.

 

 

-Based on a lecture given at a meeting of the American College of

Neuropsychopharmacology, Palm Springs, Calif., Dec 47 7 1973 . Reprinted with

permission: Am J. Psychiatry, 131:11, November 1974. Copyright 1974 American

Psychiatric Association.

 

 

References

 

1.Pauling, L.: Orthomolecular psychiatry. Science 160: 265-271, 1968

 

2.Hoffer, A.: Niacin Therapy in Schizophrenia. Springfield, Ill., Charles C.

Thomas, 1962

 

3.Osmond, H., Hoffer A.: Massive niacin treatment in schizophrenia: review of a

nine-year study. Lancet 1:316-319, 1962

 

4.Hoffer, A., Osmond H.: Treatment of schizophrenia with nicotinic acid: a

ten-year follow-up. Acta Psychiatr Scand 40:171-189, 1964

 

5.Cleckley, H.M., Sydenstricker, V,P., Geeslin, LE-: Nicotinic acid in treatment

of atypical psychotic states associated with malnutrition. JAMA 112:2107-2110,

1939

 

6.Sydenstricker, V.P., Cleckley, H.M.: The effect of nicotinic acid in stupor,

lethargy and various other psychiatric disorders. Am I Psychiatry 98:83-92,1941

 

7.Kubala, A.L., Katz, M.M.: Nutritional factors in psychological test behavior.

J Genet Psychol 96:343-352, 1960

 

8.VanderKamp, H: A: biochemical abnormality in schizophrenia involving ascorbic

acid- Int J Neuropsychiatry 2:204206, 1966

 

9.Herjanic, M., Moss-Herjanic, B.L. Ascorbic acid test in psychiatric patients.

J Schizophrenia 1: 257-260, 1967

 

10.Pauling, L., Robinson, A.B_ Oxley S.S., et a]: Results of a loading test of

ascorbic acid, niacinamide, and pyridoxine in schizophrenic subjects and

controls, in Orthomolecular Psychiatry: Treatment of Schizophrenia. Edited by

Hawkins, D., Pauling, L San Francisco, W.H. Freeman and Co., 1973, pp 18-34

 

11. Orsenberg, LE., Lilljeqvist, A.C., Hsia, Y.E.: Methylmalonic aciduria:

metabolic block localization and vitamin B12 dependency. Science 162: 805-807,

1968

 

12. Lindblad, B., Olin, P., Svanberg, B., et al: Methylmalonic acidemia. Acta

Paediatr Scand.57: 417-424, 1968

 

13.Walker, F.A., Agarwal, A.B., Singh, R.; Methylmalonic aciduria: response to

oral B12 therapy. I Pediatr 75:344, 1969

 

14.Rosenberg, LE,, Lilljeqvist, A.C., Hsia, Y.E., et al: Vitamin B12 dependent

methylmalonicaciduria: defective B12 metabolism in cultured fibroblasts. Biochem

Biophys Res Commun 37:607-614,1969

 

15.Williams, R.J.: Biochemical Individuality. New York, John Wiley & Sons, 1957

 

16.Pauling, L., Itano, ILA., Singer, S.J., et al: Sickle cell anemia a molecular

disease. Science I 10: 543-548, 1949

 

17.Hawkins, D., Pauling, L (eds): Orthomolecular Psychiatry; Treatment of

Schizophrenia. San Francisco, W.H. Freeman and Co., 1973

 

18.Hawkins, D.: Orthomolecular psychiatry: treatment of schizophrenia. Ibid, pp.

631-673

 

19.Osmond, H.: The background to the niacin treatment. Ibid,pp. 194-201

 

20.Horwitt, M.K.: Ascorbic acid requirements of individuals in a large

institution. Proc Soc Exp, Biol Med 49:248-250, 1942

 

21.Herjanic, M.: Ascorbic acid and schizophrenia, in Orthomolecular Psychiatry;

Treatment of Schizophrenia. Edited by Hawkins, D., Pauling, L San Francisco,

W.H. Freeman and Co., 1973, pp. 303-315

 

22.Stone, L: The Healing Factor: Vitamin C Against Disease. New York. Grosset

and Dunlap, 1972

 

23.Pauling, L: Evolution and the need for ascorbic acid. Proc Natl Acad Sci USA

67:1643-1648, 1970

 

24.Pauling, L: Vitamin C and the Common Cold. San Francisco. W.H. Freeman and

Co. 1970

 

25.Milner, G.: Ascorbic acid in chronic psychiatric patients: a controlled

trial- Br I Psychiatry 109:294-299, 1963

 

26.Denson, R.: Nicotinamide in the treatment of schizophrenia. Dis Nerv Syst

23:167-172, 1962

 

27.Ananth, J.V., Ban, T.A., Lehmann, H.E.: Potentiation of therapeutic effects

of nicotinic acid by pyridoxine in chronic schizophrenic & Can Psychiatr Assoc J

18:377-382, 1973

 

28.Edwin, I., Holten, K., Norum, K.R., et al: Vitamin B12 hypovitaminosis in

mental diseases. Acta Med Scand 177:689-699, 1965

 

29. Pfeiffer, C.C., Iliev, V., Goldstein, L: Blood histamine, basophil counts,

and trace elements in the schizophrenias, in Orthomolecular Psychiatry:

Treatment of Schizophrenia. Edited by Hawkins, D., Panting, L San Francisco.

W.H. Freeman and Co. 1973. pp. 463-510

 

30. Task Force Report 7: Megavitamin and Orthomolecular Therapy in Psychiatry.

Washington, DC, American Psychiatric Association, 1973

 

31.Ananth, J.V., Ban, T.A., Lehmann, ILE., et al: Nicotinic acid in the

prevention and treatment of methionine-induced exacerbation of psychopathology

in schizophrenics. Can Psychiatr Assoc J 15:15-20, 1970

 

32. Hoffer, A., Osmond, H., Callbeck, J.M., et al: Treatment of schizophrenia

with nicotinic acid and nicotinamide. J Clin Exp Psychopathol 18:131-158. 1957

 

33.Greenbaum, G.H.C.; An evaluation of niacinamide in the treatment of childhood

schizophrenia. Am J Psychiatry 127:89-93, 1970

 

34.Kelm, H.: The Hoffer-Osmond Diagnostic Test (HOD), in 'Orthomolecular

Psychiatry: Treatment of Schizophrenia. Edited by Hawkins, D., Panting, L San

Francisco. W.H. Freeman and Co. 1973, pp. 327-341

 

35.Pauling, L: No More War! New York. Dodd, Mead and Co. 1958

 

 

 

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