Download Scientific and Ethical Foundations of Nutritional Medicine. Part 1

Journal of Nutritional Medicine (1991) 2, 227-247
EDITORIAL
Scientific and Ethical Foundations of Nutritional
Medicine. Part 1—Evolution, Adaptation and Health
STEPHEN DAVIES MA BM BCH FACN
British Society for Nutritional Medicine, PO Box 3AP, London WIN SAP, UK
This article is the first in a series attempting to put into the clinical medical context an
awareness of the nutritional, environmental, psychological, cultural, technical and
industrial influences on health, and to put our perception of patients into the context of
the evolutionary progress of Homo sapiens. It will highlight some of the theoretical,
scientific and ethical aspects of current medical practice, with specific relevance to
nutritional medicine and will focus on the importance of nutrient status in modulating
adaptive responses.
Keywords: genetic expression, predisposition, environmental challenge, adaptation, evolution, nutritional
status, toxic load, xenobiotics, nutritional medicine, vitamins, minerals, essential fatty acids, amino acids,
food allergy.
DEFINITION OF NUTRITION AND NUTRITIONAL MEDICINE
Nutritional medicine is defined as [1]
the study of interactions of nutritional factors with human biochemistry, physiology
and anatomy, and how the clinical application of a knowledge of these interactions
can be used in the modulation of structure and function for the prevention and
treatment of disease as well as the betterment of health
and nutrition can be defined as
the sum of all the processes involved in taking in nutrients, assimilating and utilizing
them.
The nutritional medical approach is based on a wide range of published scientific
information and is essentially integrative, deriving concepts and knowledge from many
disciplines including physics, chemistry, anatomy, physiology, biochemistry, pathology,
pharmacology, toxicology, genetics, anthropology, palaeontology, microbiology,
molecular biology, environmental science, nutrition, food science, psychology and
sociology.
Nutrition has been perceived as a specialty of current medical practice, but nutritional
medicine integrates more comprehensively in pragmatic terms certain concepts,
perspectives and areas of knowledge, the importance of which current medical practice
underestimates. It also represents a significant broadening [2] which has been discussed
previously in this journal [3].
It is hoped that this overview will help, at least to some degree, to bridge the gaps in
communication and knowledge between those disciplines from which the theoretical and
scientific foundations of nutritional medicine are derived, and between them and
nutritional medicine to provide an integrated perspective.
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THE PRIME PRECEPTS OF NUTRITIONAL MEDICINE
A precept is defined as 'one of the practical rules of an art; a direction' [4]. The following
set of precepts were formulated and published upon the founding of the British Society for
Nutritional Medicine in June 1984 [1] and modified in the first issue of this journal in
1990, as follows.
(1) Man's diet, even in industrialized societies, may have only a borderline, or indeed low,
content of certain essential nutrients. A 'normal' diet is not necessarily a healthy or
optimum one.
(2) Requirements for essential nutrients vary from individual to individual depending on
genetic, physiological, lifestyle and other influences. What is adequate for one person
may not be adequate for another.
(3) Illness is inevitably linked with an abnormal biochemistry and an alteration in the
metabolism of nutrients and their by-products.
(4) Specific nutrients such as vitamins, minerals, essential fatty acids and amino acids, as
well as dietary manipulation in general, provide a potent means of influencing body
biochemistry and thus disease processes.
(5) Reproductive processes are nutrient-dependent and sensitive to environmental
pollution. Nutritional status of and environmental factors affecting both parents in the
preconceptional and periconceptional period, and nutritional status of and
environmental factors affecting the mother throughout pregnancy, are primary
determinants of pregnancy outcome.
This series of articles will look broadly at the theoretical background and the range of
scientific evidence upon which these precepts and thus the discipline of nutritional
medicine are based. The ethical implications for medical practice that result from
consideration of these precepts and of the underlying theoretical, philosophical and
scientific foundations, will also be considered.
It would be impossible to provide a comprehensive review of all the evidence which
substantiates or supports the validity of the nutritional medical approach. However,
references are cited that draw attention to clearly demonstrated phenomena, or refer to
those areas of research that support the validity of the viewpoints and concepts included in
this article.
It is worthwhile to begin by considering Homo sapiens in the context of our
understanding of evolutionary processes.
THE EVOLUTIONARY PERSPECTIVE—GENE EXPRESSION AS A NUTRIENTDEPENDENT, TOXIN-SENSITIVE PHENOMENON
Genes and Gene Expression
Genetics tell us that a species is the biological (genetic) consequence of successful
adaptation in terms of propagation of the species, to those environmental challenges
presented to that species in the course of its evolution. This basic Darwinian approach [5]
has been touched on previously in this journal [6] and is discussed more fully by Dubos
[7] in the context of the 20th century.
Notwithstanding any spiritual concept of Man, discussion of which is beyond the remit
of this article, the genetic concept of Homo sapiens can be summarized by stating that we
are a biological manifestation of life based upon the interaction of genetic material with
the environment in all its aspects—nutritional, toxic, other life-forms, nurturing and
destructive physical factors (temperature, atmospheric pressure, gravity, electromagnetics
etc.)—as well as the social and cultural influences and the psychological effects of all
these upon the individual and possibly also the species.
FOUNDATIONS OF NUTRITIONAL MEDICINE—PART 1
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Genetic expression is the biological mechanism by which we, as a life-form (species),
can persist physically through time. Our existence thus far is as a result of our inherent
adaptability, and can be viewed as a manifestation of the genetic legacy we have
inherited from our forebears.
Nutrition is one of the fundamental processes of life itself. Without it no life exists, nor
can any genetic expression and thus survival of any known species occur. Nutrition and
nutrient availability influence every biochemical process and determine the adaptive
capacity (see below) of an individual; thus they are of fundamental clinical relevance. To
be a physician, i.e. someone whose intention it is to assist life processes in the direction
of survival of the individual, and yet at the same time to hold the view that nutrition and
assessment of nutritional status have little or no importance in routine assessment of
patients is logically untenable. The ethical ramifications for the medical doctor of this
concept in terms of therapeutic modalities will be discussed in more detail in a later
article.
We know that our genetic material includes nuclear DNA with four purine bases, the
sequence of which determines the coding for enzyme synthesis, with synthesis and
activity turned on and off at various points in the life-cycle of a cell, group of cells or
organism [8]:
genes are switched on to a code for enzymes dictated by the needs of the organism
and hence ultimately by natural selection to ensure the right concentration of
enzyme molecules within cells. The moment the need is met, the organism
apparently activates its repression to prevent synthesis of the messenger RNA.
It is evident that genetic expression is an utterly nutrient-dependent set of processes.
Every atom of our physical body is dietarily or respiratorily (particularly in the case of
oxygen) derived. This has been discussed by Crawford & Marsh in neo-Darwinian terms
[9]. This idea is entirely compatible with more recent evolutionary theories such as that
proposed by Sheldrake [10], since phenotypes cannot develop 'accurately' without
adequate raw materials (i.e. nutrients) necessary for appropriate structure and function,
whatever other influences or mechanisms are involved in the propagation of the species.
Genes, Enzymes, Nutrients and Toxins
Enzymes require nutrients for their synthesis, and cofactors (vitamins and minerals), as
well as substrates, for their activity. Enzyme activity can be impaired or inhibited by a
shortage of nutrients as well as by toxins derived endogenously as a result of metabolic
processes, or exogenously from the environment. Deviation from the predetermined
genetic blueprint can occur as a result of nutrient deficiency [11] or excess, e.g. vitamin
A [12]. It can also occur as a result of toxic chemical or physical damage (e.g. ionizing
radiation) affecting the genetic material, or affecting the processes involved in gene
expression, or affecting enzymes or enzyme systems and other vital physical structures
(membranes etc.). The degree to which a species is successful is dependent, among other
factors, upon the degree to which individuals within the species are capable of adapting
to a non-optimum nutrient supply and toxic challenge. Man has many mechanisms by
which to metabolize toxins to render them less toxic or more readily excreted [13]; these
mechanisms have presumably been evolved to deal with naturally occurring toxic
substances present in the environment during the course of evolution. Man-made
chemicals which are absorbed into the body evidently 'piggyback' when possible on these
pre-existing detoxifying and excretory mechanisms [13]. Some medical conditions
caused by chemical exposure are outlined in Fig. 1.
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FIG. 1.
STEPHEN DAVIES
Diseases associated with exposure to environmental chemicals (after Forrester & Wolf [13]). The
dashed lines indicate that there is circumstantial evidence to suggest that chemical exposure may
play a role in the aetiology of these diseases, but this has not been proven directly. *Conditions
where diet or nutritional status are known to play a role.
There is a large body of evidence to demonstrate that nutrient deficiencies per se can
be mutagenic, and therefore potentially carcinogenic or teratogenic, and that nutrient
deficiencies can render certain chemicals mutagenic or enhance mutagenicity (see, for
example, refs [11, 14]). The corollary is also substantiated; i.e. that certain nutrients
have a protective role against toxic substances [11, 14-19].
It is interesting to note in passing that it has been known for more than 40 years that
female rats on a low riboflavin diet before mating produced low birthweight or
malformed offspring or aborted or resorbed the foetuses, although the levels were
insufficiently low to produce deficiency signs [15]. There are many other examples of
how nutrient deficiency and/or toxic load can impair mammalian reproductive capacity [
16] and this will be discussed more fully in a later article.
To lake one example—that of the mixed-function oxidase (MFO) system, vital in the
detoxification of xenobiotics (foreign chemical compounds)—the activity of which is
decreased by deficiencies of each of protein, ascorbic acid, magnesium, zinc, total and
essential fatty acids, riboflavin, energy, iron and thiamin [13]. Furthermore, oxidative
damage to DNA and biological membranes as well as damage to enzyme systems can be
reduced by the presence of adequate quantities of antioxidant vitamins, minerals, amino
acids and other dietary constituents, thereby reducing the extent of interference to
molecular processes and damage to structure [20-23].
As Hathcock [19], now of the US Food and Drug Administration in Washington, DC,
says:
Toxicology has usually been considered as a separate discipline or a subject closely
related to pharmacology; a nutritional perspective is not common. The increasing use
in food production and processing, of pesticides, growth stimulants, preservatives,
processing chemicals and nutrient supplements has resulted in a need for increased
toxicological awareness by nutritionists and other professionals concerned with food
production and utilisation and health.
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He goes on to quote Wattenburg:
In addition to altered detoxification, or biotoxification of many compounds, nutritional
deficiencies alter the primary susceptibility of cells to toxicants. Decreased
biochemical or structural integrity makes cells more easily damaged by many
toxicants, including those which are excreted unmetabolised. Protein deficiency
decreases albumin binding of many compounds. Deficiencies cause decreased rates of
cellular replacement, decreased enzyme synthesis and activation and decreased coenzyme synthesis and consequently increased susceptibility to toxicants.
The reader is specifically referred to the two volumes by Calabrese [17, 18] and the three
volumes by Hathcock [19, 24, 25] for a fuller coverage of the nutrient modulation of
toxic susceptibility.
It is clear that nutritional status and toxic load, as part of the total environmental milieu,
are important determinants of gene expression. This provides a foundation for the
discussion of adaptation as it relates to the clinical situation, and is fundamental to our
understanding of the nutritional medical approach.
Adaptation
When presented with an environmental challenge, an individual may be able to adapt to
that challenge after an initial adaptive period, called the 'alarm reaction' by Selye [26]
(see Fig. 2), and then be maintained in an adapted state until such time as adaptation can
no longer be maintained, for whatever reason. The individual then enters a stage of
exhaustion, with failure of adaptation, and can no longer be considered healthy. This is
the basic principle of the general adaptation syndrome (GAS) as described by Selye (see
ref. [26], p. 118):
Adaptability is probably the most distinctive characteristic of life. In maintaining the
independence and individuality of natural units, none of the great forces of inanimate
matter are as successful as that alertness and adaptability to change which we
designate as life—and the loss of which is death. Indeed there is perhaps even a
certain parallelism between the degree of aliveness and the extent of adaptability in
every animal—in every man.
Nutritional adaptation, whereby appropriate biochemical functions can be regulated,
maintained or enhanced in given situations in the face of a non-optimum nutrient supply
does occur, but usually at a cost (for a discussion, see refs [8, 27]). Some degree of
adaptive capacity evidently exists as regards absorption and utilization for many but not
all the nutrients studied—absorption and retention of such can be enhanced or reduced
depending on whether or not those nutrients are present in less or more than
FIG. 2. The general adaptation syndrome (GAS) of Selye [26]. In the acute phase of the alarm reaction
(AR), general resistance to the particular stressor with which the GAS had been elicited falls below
normal. Then, as adaptation is acquired in the stage of resistance (SR), the capacity to resist rises
considerably above normal. However, eventually, in the stage of exhaustion (SE), resistance drops
below normal again.
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STEPHEN DAVIES
adequate amounts necessary for optimum function (see ref. [28], p. 89). These adaptive
mechanisms again can be impaired by toxins.
Effective adaptation involving, for example, increased adrenocorticosteroid hormone
output in response to an environmental stressor, as discussed at length by Selye [26], is
dependent upon the necessary genetic programme and all those factors required for the
accurate expression of that programme—the synthesis of the necessary enzymes and their
vitamin and mineral cofactors as well as the appropriate substrates and intact membrane
structure and functions. Without all these factors intact, effective adaptation can be
impaired or inhibited, and the survival of the individual or species thereby compromised.
Adaptive mechanisms involve, among others, alterations in endocrine, neuropsychological, haematological, cardiovascular, immunological and detoxification functions
directed towards maintaining homoeostasis within certain limits. When these mechanisms
are impaired or fail, the survival of the individual is threatened; all these mechanisms
involve biochemical processes which are genetically determined and nutrient dependent.
This genetic expression is impaired by endogenously or exogen-ously derived toxins and
physical factors (e.g. radiation) damaging DNA and RNA or by interference to the
structure or activity of enzymes or the structure of other molecules as well as cell and
subcellular membranes. Thus, adaptive mechanisms can be impaired by poor nutrient
intake or assimilation, as well as by toxic excesses. The role of nutritional status in
determining the efficiency of adaptive mechanism and thus the susceptibility to toxins is
an important concept which will be developed later. The relevance of adaptive processes
to clinical and preventive medicine is discussed in the following section.
THE RELEVANCE TO CLINICAL MEDICINE OF ADAPTIVE CAPACITY, AND
THE FACTORS THAT INFLUENCE IT
General Considerations
If a person consults a medical practitioner for any reason other than for purely preventive
medical advice and education, one could, from the Darwin-Selye point of view, regard
that person as an individual member of the species Homo sapiens who has failed to adapt
to past and/or current environmental challenges. The symptoms and physical conditions
with which the patient presents to the doctor can be regarded as the consequence of
adaptive failure (stage of exhaustion—see Fig. 2) or difficulty in adapting (i.e. alarm
reaction—see Fig. 2) to those environmental challenges to which the patient is exposed.
This is a rather different perspective to that from which current medical practice is
usually viewed.
This Darwinian concept of medicine has been simply stated by Cheraskin et al. [29]
who state that 'susceptibility' (i.e. 'predisposition') times 'environmental challenge' leads
to health or disease: when predisposition is high and environmental challenge extensive
then disease ensues, and ultimately death, once the adaptive capacity of the individual has
been terminally exceeded; the lower the predisposition the greater the resistance (or
adaptive capacity) and vice versa (Fig. 3).
Predisposition
X
Environmental Challenge
FIG. 3. Formula for health or disease [29].
=
Health or Disease
FOUNDATIONS OF NUTRITIONAL MEDICINE—PART 1
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FIG. 4. An integrated approach to patient dynamics (discussed in the text).
If we take the GAS of Selye (Fig. 2) and the mechanism outlined by Cheraskin et al. (Fig.
3), we can combine the two to form a more integrated dynamic approach to patient
adaptation (Fig. 4).
This concept has been expressed, though somewhat differently, by Holdgate & Beaumont
[30].
For any species (or genetic group) it is possible to elaborate a "medicine", that is, to
describe its responses at biochemical, physiological or population level to the
variables in the environment. A variation in the conditions in the habitat, or in the
composition of an animal's food, if it is slight, causes no more than a shift in the rate
or scale of a few biochemical reactions, and the organism as a whole may adjust to
this perturbation so that there is no detectable influence on its behaviour or
physiology. A more severe disturbance may, however, bring about obvious changes
in the behaviour, metabolism or reproductive success of the whole organism. Even
this, however, may not affect the capacity of that species to maintain a viable
population in the area subject to the habitat variation—for the inherent variability of
plants and animals is likely to mean that the population has some that are more
"robust" than others in the face of the variation and the capacity of all life forms to
produce more young than are needed to replace the parents means that the
reproductive failure or the death of the most sensitive members of the population
can be made good. At biochemical, physiological and population level, organisms
have a "homeostatic" capacity—a capacity to respond to and counteract external
disturbances. The "medical science" it is theoretically possible to compile for each
species would need to document this capacity, quantitatively, for all foreseeable
perturbations, singly or in combination.
The genetic content, the accuracy and efficiency of genetic expression, social, cultural
and psychological factors, nutritional status, toxic load and pattern of environmental
challenges are unique for each individual, and we must view each patient in the context
of their life and not necessarily in terms of organ disease. As Harvey Cushing is reported
to have taught (quoted by Dubos in ref. [7], p. 342):
A physician is obligated to consider more than the whole man—he must view the man
in his world.
Each individual organism has its own unique genetic coding, its own unique nutritional
state, its own unique psychological make-up, its own unique adaptive capacity and its
own unique set of environmental challenges; all these need to be considered when trying
to understand the context in which an individual patient is living and seeking medical
advice, in an attempt to resolve what is in fact an adaptive breakdown.
This is not a new concept but was mooted some 35-40 years or so ago by Williams and
co-workers, who discussed the concept of biochemical individuality [31, 32]. Man's
adaptability and the relevance of this to this phase of our evolution has been discussed by
Dubos [7], Crawford & Marsh [9] and Vander [28].
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Predisposition
A predisposition towards failure to adapt successfully to a specific or, more usually, a
series of environmental challenges, is determined by a range of factors, including
genetics, nutritional status and psychology. We know that genetics can affect nutritional
status (e.g. transport mechanisms) and that nutritional status can determine the
effectiveness and accuracy of genetic expression [16]. It is also evident that nutritional
status can influence psychological state and that psychological state can influence
nutritional status by way of food choice, appetite and altered nutrient requirements [3335].
As has been mentioned, psychological state can also profoundly influence endocrine,
immune, neurological and cardiovascular functions, to name but a few [28]. All these
factors can influence the way in which an individual will respond to an environmental
challenge. Nutrition per se cannot be considered validly in isolation, but only in the
context of the total environment, internal and external, of the individual. The effect of the
psychological make-up on predisposition and adaptive capacity is extremely important in
any branch of clinical medicine, but is outside the scope of this article.
Environmental Challenges
Environmental challenges that represent actual or potential threats to the survival of the
individual (as well as possibly the species) include physical factors such as temperature,
humidity, atmospheric pressure and partial pressures of various gases (oxygen, carbon
dioxide, nitrogen etc.); electromagnetic fields, ionizing and non-ionizing radiation—
including sunlight; infective, parasitic and toxic components in our food, water, air and
general environment—including social pollutants such as alcohol, tobacco, caffeine and
industrial or agricultural pollutants such as pesticides, herbicides, fungicides, industrial
effluent etc.—and medical drugs (see Table 1).
Environmental factors evidently play an important part in health and disease. In light of
the extent to which our air, water, food supply and living environment have been, and
continue to be, polluted by man-made chemicals, our approach to the
TABLE 1. Types of environmental challenge
(1) Naturally occurring toxicants in food, air, water and environment [36]
(2) Man-made chemical exposure.
(i) Industrial exposure to individuals
(ii) Industrial effluent polluting food, air, water and environment [17, 18, 37]
(iii) Agrichemicals (Table 2)
(iv) Food processing chemicals (Table 3)
(v)
Chemical treatment of water supply (fluoride, chloride etc) [38]
(vi)
Domestic pollutants (detergents (including toothpaste) cleaning chemicals, aerosol sprays,
building materials, e.g. formaldehyde) [39] (vii) Dental material (e.g. mercury) [40, 41] (viii)
Medical drugs and illegal drugs [44] (ix) Social toxins (e.g. tea, coffee, alcohol, tobacco)
(3) Ionizing and non-ionizing radiation
(4) Inadequate or excessive sunlight [42]
(5) Electromagnetic pollution [43]
(6) Noise pollution [37]
(7) Psychological [28, 35]
(8) Infection and infestation
(9) Inappropriate level of physical activity (excessive or inadequate)
(10) Sleep deprivation
(11) Seasonal
(12) etc.
FOUNDATIONS OF NUTRITIONAL MEDICINE—PART 1
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patient should include an awareness of these aspects of the environmental challenge. It is
of obvious relevance when considering industrial or occupational exposure and, while this
has been embraced by current medical practice, what has not been embraced is the degree
to which lesser levels of a combination of large numbers of environmental pollutants can
affect an individual's health.
Consideration of both the predisposing factors and the environmental challenges
occurring in a particular patient's life are necessary if a medical practitioner is to achieve a
broader understanding, in evolutionary and practical therapeutic terms, of the context in
which an individual patient finds themselves in a given clinical situation.
A further mechanism to be taken into consideration, arises when predisposition is
reduced and adaptive mechanisms are compromised, and environmental challenge tends to
be greater as a result, e.g. opportunistic infections in immune-compromised patients; a
dwindling spiral of ill health subsequently ensues. Some defence systems against
environmental challenge are outlined in Table 2.
Table 2. Some defense systems against environmental challenge [13]
Environmental Challenge
Defence System
Biological agents
Bacteria
Hormonal and cellular response
Viruses
to the immune system
Toxins
Parasites
Yeasts
Chemical agents
Enzymatic detoxification systems
Foods
DNA repair enzymes, membrane proteins Industrial chemicals
Drugs
affecting drug accumulation
Environmental chemicals
Pesticides
Physical agents
Heat
Stress response systems, glutathione,
UV irradiation
DNA repair enzymes, skin pigmentation
Oxidative stress
Maladaptive Responses
As Vander [28] succinctly states:
It is easy enough to understand how a given environmental threat can cause disease or
death if there is no adaptive response at all to it, or if the response is simply not up to
the task, as for example, in an overwhelming bacterial infection. What is surprising is
that the response itself may be outright damaging, i.e. maladaptive.
In many cases this maladaption is an unavoidable consequence of the body's
complexity. The response to a stressor automatically alters many other components of
body function, sometimes in a harmful way. For example... when the body responds
adaptively to a harmful foreign chemical by increasing the rate at which the body
breaks down the chemical, the rate at which certain essential endogenous chemicals are
broken down is also enhanced, with potential harmful results if the endogenous
chemical is already in short supply.
On yet another level of complexity, acclimatization to one stressor may influence the
ability to respond to a second different stressor. This is a fundamental concept, i.e.
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STEPHEN DAVIES
FIG. 5. Integrated scheme of life function.
that of 'total load' of stressors, giving rise to a breakdown of adaptive mechanisms and the
development of disease. This has been discussed at length by Randolph [45]. To further
discuss maladaptation, Vander goes on to say [28]:
Another type of maladaptation occurs when a response which is highly adaptive in the
short term turns out to be harmful if continued for long periods. For example, low
levels of irritating air pollution increase mucus production in the airways, an adaptive
response which helps prevent entry of these chemicals into the blood. However over
long periods of time the accumulation of mucus production may predispose to
infection in the airways and to serious lung disease.
A further type of maladaptive response is characterised by allergies such as hay
fever, which is an inappropriate or excessive response to pollens, which can give rise
to miserable symptoms. Immunological responses to bacterial infection for example,
can also be appropriate but may be excessive where the defences against a microbial
invader may result in destruction not only of the invader but also of the body's normal
cells and tissues.
There may well be a common denominator to many of these maladaptive responses,
namely that most people now live in environments which because of human
intervention, are very different from the environments in which humankind evolved.
It should not be surprising therefore that physiological activities and responses which
were selected by evolution because of their adaptiveness in one environment might
prove to be maladaptive when the environment changes.
In practical terms, prevention and treatment of disease in this medical model should
involve intervention to reduce predisposition (i.e. increase resistance) and reduce
environmental challenge; in other words, the application of a more integrated approach to
patient management which is outlined in Fig. 5.
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237
BASELINE
FIG. 6. Adaptive capacity and symptom threshold (adapted from Brennerman [46]). * In excess, these
become toxic chemicals.
ADAPTIVE CAPACITY AND HEALTH
As we have seen, the lower the predisposition the greater is the adaptive capacity, and
thus resistance in health terms, to the ill-effects of environmental challenges. The
corollary would also appear to be true: the higher the predisposition the less are the
adaptive capacity and resistance to ill-effects from environmental challenges. In order to
illustrate a clinical application of this more integrated approach, let us take a
hypothetical case of childhood asthma.
An Example—Childhood Asthma
Another way of looking at predisposition and adaptive capacity is outlined in Fig. 6;
application of this model to patient assessment, which can be expanded to include all
sorts of different types of environmental challenges (see Table 1), is very useful in
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STEPHEN DAVIES
SYMPTOMS
BASELINE
FIG. 7. Adaptive capacity, predisposition and precipitation: a case of childhood asthma. A, Before
treatment—reduced adaptive capacity: parents arguing precipitates asthma attack. B, After
treatment—increased adaptive capacity: parents arguing does not precipitate asthma attack.
trying to determine those factors involved in contributing to the patient's adaptive
breakdown. Let us take, for example, the case of a nine-year-old boy, who has an asthma
attack every time he is in bed and his mother and father have a noisy argument
downstairs. In an analysis of this child's situation we can say that asthma can be
associated with selenium deficiency [47] and with vitamin B6 deficiency, and may be
improved by vitamin B6 supplementation [48]; magnesium deficiency increases
bronchial reactivity [49, 50] and destabilizes mast cells [51]. We also know the
following: a significant percentage of asthmatic children are intolerant to cow's milk and
many are allergic to house dust mites [52]; some food colourings, e.g. tartrazine, can
cause bronchospasm in susceptible individuals [52, 53] and can cause an increase in
urinary zinc excretion with increased risk of zinc deficiency [54]; certain types of
toothpaste can provoke bronchospasm [55]; certain aerosol bronchodilators contain
chemicals (for example Ventolin, Alien & Hanbury UK, contains trichlorofluoromethane and dichlorodifluoromethane as propellants) which themselves can provoke bronchospasm in susceptible individuals [56]; essential fatty acid (EFA) metabolism is
impaired in atopic individuals [57] and EFA metabolism determines the balance of
proinflammatory prostaglandins and leukotrienes and the anti-inflammatory prostaglandins [57]; cell membranes, including bronchial mucosal mast cell membranes, are
unstable if antioxidant supply in the diet is inadequate [20]; stress and anxiety can
FOUNDATIONS OF NUTRITIONAL MEDICINE—PART 1
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precipitate an attack; some asthmatics react to sulphites [58]; under normal circumstances, sulphur dioxide in air, sulphites in the diet and those created endogenously as
part of normal sulphur metabolism are usually oxidized by the molybdenum-dependent
enzyme sulphite oxidase [59]. If insufficient molybdenum is present [60], the activity of
the enzyme is reduced and sulphites accumulate and spill over into the urine in
measurable quantities—this is a functional test for molybdenum deficiency [61, 62].
Asthmatic children may also have gastric hypochlohydria [63]. As can be seen in Fig. 7,
there is a cumulative effect of all these individual components, bringing the patient up
towards the symptom threshold and away from the baseline, with a reduced 'residual'
adaptive capacity for whatever environmental challenge the individual may be subjected
to—in this case the stress of the parents arguing acts as the precipitating factor.
Let us imagine that, for the second time, the family doctor is called out to the house to
see this upset nine-year-old boy who is wheezing badly, and that both visits have been
after the parents have been arguing—a stressful situation for the child (not to mention the
parents). The doctor may assume that the asthma attack is psychosomatic in origin but
may consider other things: the doctor may check for the presence of a chest infection,
may give antibiotics (hopefully free of colourings) or a 'bronchodilator' drug or steroids,
marriage counselling for the parents or family therapy for the family.
There is, however, another approach based upon a consideration of the adaptive
capacity of the child and a knowledge of those factors known to be of possible relevance
in the predisposition to asthma. The acute situation, if life threatening, should be dealt
with using the appropriate medication. At a later point in time the doctor can work with
the child and his parents to ensure adequate dietary intake, with emphasis on
micronutrient-dense unrefined foods, to check the adequacy of status of selenium,
vitamin B6, magnesium, zinc, molybdenum and those cofactors required for effective
essential fatty acid metabolism [57]. The doctor may give nutritional supplements where
appropriate, and advise the trial of a diet free of cow's milk and minimised house dust
mite exposure. The child may well find later (point B in Fig. 7) that his parents can argue
without him experiencing an asthma attack. However, the relative contribution of each
component, and the components themselves, may vary between different asthma sufferers
and for the same sufferer at different points in time. Once again the individual has to be
borne in mind, and generalization as regards aetiology of a specific medical condition in
a particular individual should be avoided.
In principle, the closer to the baseline in Figs 6 and 7, the greater is the adaptive
capacity; the closer to the symptom threshold the poorer is the adaptive capacity. As
medical practitioners, we can, using this model, help ourselves and the patient to
understand the various addressable factors that might result in an increased adaptive
capacity. This in turn could lead to an effective multifactorial therapeutic intervention
which may result in a disappearance of the clinical symptoms and thus avoid having to
resort to pharmaceutical (xenobiotic) drugs. The interface between the nutritional medical
approach and the prescribing of pharmaceutical drugs as well as drug-nutrient
interactions will be covered in a later article.
From our professional knowledge and experience, we can leam from the clinical and
family history, physical examination and laboratory and other special investigations those
factors most likely in a particular patient to be contributing to a reduced adaptive capacity
to the total sum of all environmental challenges to which the patient is exposed.
In summary, genetic content, genetic expression, psychological factors, environmental
challenge and the pivotal role of nutritional status as a major modulator of these
influences on the survival of an individual or species are primary concepts upon which
the discipline of nutritional medicine is based and which must be grasped before the
nutritional medical approach can be understood.
240
STEPHEN DAVIES
IS THE CURRENT 20TH CENTURY WESTERN DIET ADEQUATE TO MEET THE
CURRENT ENVIRONMENTAL CHALLENGES?
We will now consider in general terms, those factors that influence predisposition,
environmental challenge and adaptive capacity.
General Considerations
In considering the health of Homo sapiens in light of the interplay between predisposition
and environmental challenge and the importance of nutrition as outlined above, it would
seem worthwhile to compare the nature of the modem 20th century western diet with the
(albeit postulated) diet that Homo sapiens consumed during the greater part of his
evolution. One such discussion has been presented by Eaton & Konner [64] who state the
following:
The human genetic constitution has changed little since the appearance of truly
modern human beings, Homo sapiens sapiens, about 40,000 years ago. Even the
development of agriculture 10,000 years ago has apparently had a minimal effect on
our genes. Certain haemaglobinopathies and retention of intestinal lactase into
adulthood are "recent" genetic evolutionary trends, but very few other examples are
known. Such developments as the Industrial Revolution, agribusiness and modern
food processing techniques have occurred too recently to have had any evolutionary
effect at all. Accordingly, the range of diets available to pre-agricultural human
beings determines the range that will still exist for men and women living in the
20th century—the nutrition for which human beings are in essence genetically
programmed.
TABLE 3. The main events of human evolution modified from Pilbeam [65] and Baton & Konner [64]
Years
Ago
200
Event
Industrial Revolution
5000
Introduction of cupellation
(metal extraction—lead etc.)
Holocene
10 000
Agricultural Revolution
Late pleistocene
45 000
Homo sapiens sapiens—
anatomically modem man appears
H. sapiens Neanderthalis appears
80 000
Middle Pleistocene
400 000
1-6 million
2-0 million
Early Pleistocene
Pliocene
4.5 million
Archaic Homo sapiens appears
Homo erectus present
Homo habilis present
Australopithecine divergence
Bipedal Australopithecus
afarensis present
Late miocene
7.5 million
Hominid-pongid divergence
(inferred from molecular data)
11 million
Middle miocene
African and Asian Hominoids diverge
Early miocene
Hominoid radiation begins
17 million
24 million
Palaeolithic period
first manufacture of
stone tools to shortly
before the development
of agriculture
TABLE 4. Comparison of the late palaeolithic diet [64], the current UK diet [66] and Dietary Reference Values [67]
Current UK
Late
Palaeolithic diet'
Total dietary energy (%)
Protein
Carbohydrate
Fat
P:S ratio
Cholesterol (mg)
Fibre (g)
Sodium (mg)
Calcium (mg)
Ascorbic acid (mg)
a
34
45
21
1. 41
591
45. 7
690
1580
392
adult diet (mean)
Male
Female
14. 1
41. 6
37. 6
0. 40
390
24. 9
3376
937
66. 5
15. 2
43. 0
39. 2
0. 38
280
18. 6
2351
726
62. 0
Dietary Reference Value
adult
Male
55. 5
50
35
(0. 4)
(—)
18/34
1600
525/700
25/40
Female
45. 0
50
35
(0. 4)
(—)
18/34
1600
525-700
25/40
EAR/RNIb
RNI (no EAR made)
EAR/RNI
EAR/RNI
Assuming the diet contained 35% meat and 65% vegetables.
(a) P:S ratio denotes (polyunsaturated):(saturated) fats.
(b) Dietary Reference Values—the term used in ref. [67] for the various categories of nutrient intakes discussed.
(c) EAR (estimated average requirement)—the estimate of the average requirement or need for food energy or a nutrient.
Clearly, many people will need more than the average and many people less ref. [67].
(d) RNI (reference nutrient intake)—the amount of a nutrient that is enough for almost every individual, even someone who
has high need for the nutrient. This level of intake is, therefore, considerably
RNI of a nutrient, they are most unlikely to be deficient in that nutrient.
b
Fibre is referred to as non-starch polysaccharides in ref. [67].
242
STEPHEN DAVIES
These considerations would appear to have strong relevance to the dominant health
problems in modem western industrialized society: chronic degenerative disease—coronary heart disease, hypertension, diabetes, cancer, arthritis, mental disease—are
virtually unknown among the few surviving hunter-gatherer populations whose way of
life and eating habits most closely resemble those of pre-agricultural human beings. The
main events of human evolution are outlined in Table 3.
A Comparison of Palaeolithic and 20th Century Western Diets
A comparison of the postulated late-palaeolithic diet [64], the current UK diet [66] and
UK, Dietary Reference Values [67] appears in Table 4, highlighting the major differences
between them.
We are genetically programmed for the palaeolithic nutritional pattern in terms of
hunting and gathering [7, 66] as regards food choice and availability. However, it is
apparent that the nutrient content of and nutrient availability from the modem food
supply is different from that in palaeolithic times. Some differences are highlighted in
Table 4. One example is the domestication of animals, birds and fish which is associated
with a reduction in omega-3 fatty acids, eicosapentaenoic acid (EPA) and
docosohexaenoic acid (DHA), as well as a reduced total polyunsaturated fatty acid
TABLE 5. Factors that may influence the nutrient content of and bioavailability of
nutrients from the modem food supply
(1) Domestication of animals and fish and intensive farming procedures
—alteration in essential fatty acid content of meat
—alteration in saturated fat content of meat
—use of steroid and other hormones
—use of antibiotics in animal feed
—use of tranquillisers and beta-blockers to reduce stress
—deprivation of sunlight
—deprivation of free-range feeding pattern
—hybridization to increase yield rather than enhancement of nutritional quality
—feeding of offal to herbivores
—overcrowding
—salmon and trout fanning: overcrowding, high incidence of infection and
infestation, interference with migratory and reproductive pattern of behaviour,
use of chemical wormers
(2) Agrichemical usage
—pesticides, herbicides, rodenticides, fungicides
—hybridization of plant species to increase yield and resistance to
agrichemicals rather than to enhance nutrient content
—nitrate fertilizers rather than soil remineralization: nitrogen fertilizers
interfere with mineral uptake and bioavailability
(3) Food processing and packaging
—refining of wheat and sugar which reduces trace mineral and vitamin content
—effects of storage and heating on nutrient content
—food irradiation
—contamination of food by packaging procedures and materials
—addition of man-made chemicals which may alter the nutrient content and
bioavailability:
flavour enhancers, colourings, flavourings, stabilizers, emulsifiers, binders,
preservatives, etc.
(4) Food preparation
—effect of heat and storage
—effects of microwave ovens
(5) Medical drugs
FOUNDATIONS OF NUTRITIONAL MEDICINE——PART 1
243
content [64]. Intensive livestock farming of pigs and chickens in particular, where the
animals are kept indoors in overcrowded conditions, is associated with nutrient
deficiencies of these animals and problems with infection [68-70]. Food processing and
refining techniques further compromise nutrient content [71-74] as do intensive farming
techniques which result in soil demineralization [75]. Agrichemicals and other environmental pollutants find their way into the food chain [68-70, 76] and further disrupt the
nutrient value of the foods and stress our detoxification and excretory mechanisms (see
Tables 5 and 6). This will be discussed in more detail later in this series of articles.
Table 6. Main types of food additives (from London Food Commission [70])
(1) Cosmetic additives
Approx number
Colours
Flavours
Flavour enhancers
Sweeteners
Texture modifiers (e.g. emulsifiers, stabilizers)
50
3500+
7
13
70
3640+
(2) Preservatives
Preservatives
Antioxidants
Sequestrants
43
13
7
63
(3) Processing Aids
Total additives
91
3794+
Does the Modern Food Supply Increase Predisposition and Actually Constitute a
Significant Environmental Challenge?
If the nutrient content of and the bioavailability of nutrients from the modern food supply
is less now than in paleolithic times, this could lead to a compromise of nutritional status,
an increase in predisposition and a concomitant reduction in an individual's adaptive
capacity. It would therefore have profound relevance in assessing patients.
Food choice also has an obvious impact on nutritional status and is governed by a range
of influences including the personal, social, cultural, economic and commercial (e.g.
advertising, packaging), and not just the physiological nutritional demands of the
individual. (Thus it could be said that advertising can have an impact on genetic
expression!)
The following can contribute to the compromising of the nutritional quality of our food
supply:
—modem intensive farming techniques can result in soil demineralization and 'sterilization';
—the widespread use of artificial fertilizers can influence mineral uptake by plants and
can reduce the bioavailability of minerals;
—the widespread use of agricultural and farming chemicals (pesticides, hormones etc.,
see Table 5) may alter the nutrient content of and bioavailability from foodstuffs;
—the domestication of animals and the intensive way in which they are reared;
—the use of xenobiotics in food processing and the reduction in nutrient content as a
result of refining procedures (e.g. wheat, flour and sugar).
244
STEPHEN DAVIES
Furthermore, food choice can be influenced by nutritional status. Zinc, for example, is
critical in its influence on appetite, taste and smell [77] and can affect food choice;
zinc deficiency can have an influence on food choice in the direction of 'high-impact'
tasting foods [80], i.e. those with flavourings, flavour enhancers, a high salt or sugar or
sweetener content, processed or refined foods, and these in turn can give rise to a reduced
micronutrient intake. It may well be that zinc deficiency is more common in western
industrialized societies than was previously estimated: in the latest UK dietary survey [66]
the mean dietary zinc intake (including those taking supplements) was 11-4 mg per day
for men and 8-4 mg per day for women, representing 76% and 56%, respectively, of the
United States Recommended Daily Allowance (US RDA) [74]. However, the latest report
of the Dietary Reference Values in the UK set the required nutrient intake for zinc
extraordinarily low at 9-5 mg per day for men and 7-5 mg per day for women [67].
The above, in conjunction with the potential toxic effects of all the many thousands of
agricultural and food processing chemicals and industrial pollutants that find their way
into our food and water supplies, all mitigate towards the modem food supply having the
effect of increasing predisposition and environmental challenge. This has substantial
implications for clinical medicine and public health since it tips the equation (Figs 3 and
4) in the direction of non-adaptation or only partial adaptation, and the consequent
increased likelihood of compromized function and ill health.
Food and Chemical Intolerance as Maladaptive Processes
A further viewpoint, which can enhance a physician's understanding of disease
mechanisms in a particular patient, is to consider that major differences between the
palaeolithic diet and the modem diet could represent an environmental challenge requiring
adaptive processes, and that a certain percentage of individual members of the species
may fail to adapt to these challenges or may exhibit maladaptive responses. The physician
should consider these differences, not just in terms of nutrient and xenobiotic content but
in terms of the actual foodstuffs and frequency of consumption.
For example, wheat and dairy products are consumed by most of us on a daily basis.
However, as hunter-gatherers prior to the development of agriculture approximately 10000
years ago (see Table 3), we would have come into contact with them less regularly and in
much smaller quantities. Thus, it is entirely reasonable to postulate that a percentage of
man's ailments may be due to a failure to adapt or maladaptive responses to such
environmental challenges. This appears to be the case in a certain percentage of patients
since wheat and dairy products are among the food items most commonly implicated [79]
in a range of clinical conditions, including rheumatoid arthritis, irritable bowel, asthma,
eczema, migraine and mental disorders etc. to name but a few [81]. The same can be said
of sucrose, which was present in our diet in only relatively small quantities until a couple
of hundred years ago—a mere 'blinking of the eye' in evolutionary terms—and which has
been implicated as being a significant contributing factor in a wide range of conditions
that afflict western man [73].
Various mechanisms involved in the development of food and chemical intolerances and
the impact that they have in the development of ill health will be discussed in a later
article.
CONCLUSIONS
In summary, the nutritional medical approach is based on the concept of genetic-environmental interaction and the pivotal role of nutrition in modulating this interaction. It is
based on the premise that the modern diet is not necessarily adequate for
FOUNDATIONS OF NUTRITIONAL MEDICINE—PART 1
245
optimum modulation of the gene-environment interaction and that preventive and
therapeutic measures can be formulated as a result of adopting this premise. It does not
assume, as current medical practice generally does, that the nutrient content of the current
food supply is adequate to meet the demands placed on an individual by the chemical
pollution of our environment, water, air and food supply. By not making this assumption
one looks at the patient in terms of adaptive breakdown, and one looks at the range of
possible addressable factors that might be contributing to that failure of adaptation,
including the presence of subclinical or clinical nutrient deficiencies or toxic overload.
In further articles in this series, to appear in future issues of the journal, further
consideration will be given to the following:
—the possibility of widespread subclinical nutritional deficiencies in Western society;
—the impact of partial adaptive breakdown and consequent ill health on nutrient
demands;
—maladaptive and other responses to food and common toxicants;
—the extent and nature of important widespread toxicants (lead, aluminium, mercury,
pesticides, food additives, detergents, industrial, occupational and domestic pollutants);
—the role of long-term use of pharmaceutical drugs in the nutritional medical model;
—the role of nutritional medicine principles in preventing birth defects and handicap, and
the procedures for licensing new chemicals for agrichemical, food processing,
domestic, industrial or pharmaceutical use.
Further consideration will also be given to the possible interactions between accumulated
toxicants, risk-benefit assessment of nutritional supplementation, ethical ramifications in
terms of medical practice and directions in which we, as medical practitioners, can go in
the light of this broader, more integrated approach.
Submissions for publication in this journal are invited, that relate to any aspect of this
proposed medical model, in the form of letters, original research, critical reviews and
case histories.
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