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Abram Hoffer, M.D., Ph.D (1917- 2009)
in schizophrenia. As a result, this entire
controversy and emerging tranquilizers
on the market led the adrenochrome
theory and resulting therapy falling into
oblivion. Nevertheless, a seed of a new
interest into mechanisms and effects
catecholamines and their metabolites
might have on the body was planted. In
recent years catecholamine-induced
toxicity has been implicated and rese-
arched in three fields so far: neurology,
psychiatry and cardiology.
Hoffer’s work has been continued by
many followers among which the work
of Carl Pfeiffer at the Princeton Brain
Bio Center in USA holds one of the most
prominent places. He observed that
most people with mental illness were
low or deficient in zinc or had a copper-
zinc imbalance, a finding duplicated by
other researchers. He also established
five groups of mental disorders related
to chemical compound found in blood
and urine, cerebral allergy which inclu-
des wheat- gluten allergy and nutritional
Orthomolecular medicine and
psychiatry today is an independent
branch of medicine present worldwide
with their own international and local
associations. Its “Journal of Orthomo-
lecular medicine” has a goal to educate
health practitioners through numerous
high quality scientific publications in
the field.
Since the initial treatment of
schizophrenia orthomolecular therape-
utic methods have been claimed as
effective in treating a broad spectrum
of other psychiatric and neurological
diseases from bi-polar, depression, be-
havior problems, autism, tardive dyski-
nesia to ADD/ADHD , MS, Parkinson’s
disease, epilepsy, addictions etc. Ortho-
molecular medicine also has extended
into other medical areas where condi-
tions like arthritis, allergies, digestive
problems, cancer and various cardio-
vascular conditions have been treated
with promising results.
The concept of orthomolecular me-
dicine is based on several principles
which can be narrowed down to two
main ones:
nutrition with optimal supple-
(usually with large quantities)
biochemical individuality.
is the cornerstone of ort-
homolecular medicine. Since the human
body should constantly be supplied by
food in order tomaintain life, the choice
of food is one of the major factors that
determine the body’s chemistry. Food
intake reflects on the molecular level
of the cell and the tissue microenvi-
ronment and consequently plays a role
in delicate, but always ongoing dyna-
mics between normal physiology and
” and “
Primum non nocere
” are in-
corporated in this concept.
In practice, orthomolecular therapy
is focused on correcting one’s nutritio-
nal faults whether there is a deficiency
in micronutrients, consumption of
improper or harmful food or excess of
macronutrients. Most commonly more
than one factor is involved. Recommen-
dations are directed toward avoidance
as much as possible of processed, pre-
pared and refined food that is stripped
of essential nutrients. Basically, it means
that the diet should exclude food with
additives, artificial flavor enhancers,
food coloring and preservatives. Also
simple sugars found in cookies, pastries,
cakes etc. are considered one of the
major culprits for health problems and
are banned from the patient’s diet. Re-
strictions are also made in the amount
of consumed saturated fatty acids.
Further on, determining the food to
which the patient is allergic or intolerant
is a must. This rule pertains to the so
called „healthy food” as well. Recogni-
zing the fact that food which is benefi-
cial to one person can be detrimental,
even fatal to the other, orthomolecular
medicine respects the fact that each
person is unique and consequently
should be treated individually. A good
example is citrus fruits such as oranges,
lemon, grapefruits, kiwi etc. Because of
a high content of Vitamin C and flavo-
noids they are highly recommended
food. However, for a person who has
adverse reaction to them, avoidance is
required not only to prevent allergic
reactions, but also to omit exacerbation
of the patient’s underlying disorder.
Consuming bread or pasta made of
whole grain, organic flour without addi-
tives and coloring is another example.
It is generally considered healthy food,
but for an individual who is gluten in-
tolerant it can cause variety of symp-
toms, usually gastrointestinal, but in
some cases the process can extend over
to other systems, including the skin,
musculoskeletal, nervous system etc.
with or without the GI tract involve-
In addition to diet adjustment, ort-
homolecular therapy advises mega
nutrient therapy which includes large
doses of essential vitamins, minerals,
trace minerals, amino acids and essen-
tial fatty acids in order to correct the
presumed chemical imbalances. Eviden-
ce based research shows that majority
of current food supply is grown in nu-
tritionally depleted soil. To make things
worse, this kind of food is further pro-
cessed, refined and additionally stripped
of its crucial nutritive constituents.
Although the food on the shelves
satisfies, even exceeds the caloric needs
of general population in the Western
hemisphere, it could paradoxically cause
malnutrition in terms of inadequate
amounts of essential micronutrients.
The notion that modern diet does not
provide the optimum concentration of
necessary nutrients for an individual is
shared now worldwide by the experts
in the field. Furthermore, a precursor or
substrate may not be utilized comple-
tely or in part because of deficiencies
in enzymes or coenzymes in individual
metabolic pathways. These factors call
for supplementation in quantities much
higher than recommended in order to
rectify one’s specific deficiencies in these
nutrients. Today the main supplements
used in orthomolecular psychiatry are
vitamin B3, B6 and B12, folic acid,
vitamin C with flavonoids, vitamin D
and E, essential amino and fatty acids,
and certain minerals.
Biochemical individuality
is the
concept evolved from the work of Roger
J. Williams, discoverer of vitamin B5, in
1956 where he suggested that bioche-
mical pathways of the body have signi-
ficant genetic variability and many di-
seases such as atherosclerosis, cancer,
schizophrenia or depression were asso-
ciated with specific biochemical abnor-
malities which were either causal or
contributing factors of an illness. While
studying alcoholics, Williams found that
the dietary deficiencies arose not pri-
marily because of failure to eat satisfac-
tory food, but rather of the genetic
patterns which made these individuals
prone to the development of crucial
deficiencies. His findings explain partial
„genetic block” where the capability of
producing a specific enzyme is not en-
tirely lost, but it is impaired to such an
extent that augmented nutritional
requirements develop whichmay be for
a specific vitamin, amino acid, mineral
or other metabolic substance. He
termed these types of diseases „gene-
totrophic” diseases.
This theory is not only adopted by
orthomolecular medicine but it is also
confirmed in current research. Ames
and al. suggest in a paper published in
2002 that as many as one third of mu-
tations in a gene results in the corres-
ponding enzyme having decreased
binding affinity for a coenzyme, resulting
in a lower rate of reaction. About 50
human genetic diseases due to defecti-
We are stepping into a new era where
new trends in current medical practi-
ce emphasize nutrition in prevention
of many conditions and see it as a
valuable support to the established
medical therapies. In addition, practi-
cal experience has shown that treating
a sick person rather than disease one
suffers from has better chances for
Orthomolecular medicine has reco-
gnized importance of both, nutrition
and individuality, and incorporated
them into its concept since the be-
ginning. Of particular interest is imple-
mentation of nutrition and vitamins
and other natural constituents in neu-
rology and especially in psychiatry.
Psychiatric disorders are looked at from
the biochemical prospective, rather
than only psychological or social. Ort-
homolecular psychiatry holds that
metabolic abnormalities within the
nervous system, mostly due to a genetic
error, can bring about many psychiatric
manifestations and as such can be
treated with substances naturally occu-
rring in the body and food. Vitamins,
particularly B3 and C, as integrative and
crucial part in these chemical processes,
are administered in optimal, very often
in mega doses in order to overcome
these abnormal metabolic pathways.
Schizophrenia, as well as other mental
disorders, according to this concept,
arise in those individuals who are rela-
tively deficient in certain vitamins and
most likely some essential minerals and
other necessary natural substances. In
another word, the need for these essen-
tial substances are higher than in other
people in order to maintain normal
physiology and production of neuro-
According to scientific evidence so far,
more investigation regarding a link
between nutrition and supplementati-
on, genetic aberrations and neurological
and psychiatric disorders is indeed
warranted and needs more attention in
the future. It could lead to clearer un-
derstanding how nutrition and supple-
mentation affect nervous system and
mental health which in turn may facili-
tate development of new dietary pro-
tocols for prevention and therapy of
neurological and mental illnesses, as
well as healthier ageing with superior
quality of life.
pathological physiology of the body.
According to Pauling, the functioning
of the brain and nervous tissue is pro-
bably more dependent on molecular
composition then is functioning of other
organs and tissues. He indicates that
psychosis associated with pernicious
anemia, for example, may manifest itself
in a patient for several years before the
other manifestations of this disease
become noticeable. Also, increased
incidence of B12 deficiency detected in
patients admitted to psychiatric wards
points toward the possibility that the
mental disease is rather a result of this
Along this line, Pauling argues that
other deficiencies in „vital substances”
might be entirely or partly responsible
for many cases of psychiatric illnesses.
Another reason why orthomolecular
therapy made nutrition its first choice
is derived from long-lasting clinical
experience and observation that nutri-
ent-related disorders are usually tre-
atment responsive or in some cases even
curable.In addition, with few possible
exceptions, nutrients have showed low
level of side effects. In this way both
principles of Hippocrates ”
Let the food
be your medicine and medicine be your
What is food for one, is to
others bitter poison
Lucretius Titus Carus
c.99 BC-55 BC, Roman poet and
ve enzymes can be remedied or ameli-
orated by the administration of high
doses of the vitamin component of the
corresponding coenzyme, which at least
partially restores enzymatic activity .
Along with this concept, orthomole-
cular medicine considers nutritional
needs of each patient individually and
treats them accordingly. It has been
shown in practice that a large propor-
tion of today’s population requires an
intake of certain nutrients far beyond
the recommended daily allowances
(percent daily value-DV, presumed to
prevent severe deficiency disease) to
maintain optimal health.
Therefore, in the course of the tre-
atment, each patient is closely observed
and dose-titrated. The initial dose of a
supplement is gradually increased to
the „patient’s tolerance” which varies
from patient to patient. For instance, in
case of vitamin C the dosage is increased
up to the level which can cause loose
stool and then it is reduced just to reach
the safe amount. Likewise, niacin is ti-
trated to the individual nausea and/or
vomiting level and adjusted just below
this amount where it can only bring the
beneficial effects.