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Paleolithic Nutrition and Multiple Sclerosis
Ashton Embry
Numerous diets have been proposed to be of benefit for MS (1) but none of these have been
rigorously tested under clinical conditions and more importantly none have been supported
by an underlying immunological basis. There is substantial evidence which indicates that a
Paleolithic diet regime may be of benefit in modulating autoimmune disease, including MS.
In 1985 Eaton and Konner (2) proposed that foods added to the human diet during the past
10,000 years when agricultural practices were adopted (Neolithic) are potentially
incompatible with the human genetic structure which had slowly evolved with and adapted
to a diet of lean wild meat, fruits and vegetables over 2 million years. Thus it may not be
unreasonable to hypothesize that an incompatibility exists between genetically determined
human dietary requirements and the new foods ushered in by the agricultural revolution
such as dairy, grains, legumes, yeast and high saturated fat meats. This genetic discordance
has been hypothesized to be, in part, responsible for the increased occurrence of a variety of
chronic degenerative diseases including heart attacks, stroke, some cancers, and type 2
diabetes (2). There is also substantial epidemiological, clinical and animal data which
supports the notion that the fundamental underlying etiology of autoimmune disease stems
from a genetic incompatibility between the human immune system and environmental
factors. Pathogenic organisms including bacteria and viruses have long been suspected to be
involved in the development of autoimmune disease (including MS). Over the past decade,
evidence has increasingly suggested that these organisms may elicit certain types of
autoimmune disease in genetically susceptible individuals via the process of molecular
mimicry (3, 4, 5, 6). There is also an emerging body of evidence to indicate that dietary
antigens may also serve as mimicking antigens in the etiology of autoimmune disease (7, 8, 9,
10). Further, there is compelling evidence from both human and animal trials to indicate
that dietary glycoproteins (lectins) found in common food stuffs, such as grains and legumes
alter intestinal physiology and allow luminal pathogenic antigens access to peripheral
tissues. (11, 12, 13).
Epidemiological Data
A notable aspects of MS is the distinct variations in disease prevalence throughout the
world (14). It has a high prevalence mainly in USA, Canada, western Europe, New Zealand
and Australia, a pattern mainly related to genetic susceptibility (European ancestry). In this
regard it has been established that susceptibility to MS is associated with MHC class II
molecules most notably DR2 and DQ1 (HLA DRB1 1501, DQA1 0102, DQB1 0602
haplotype) (15, 16, 17). However it would appear that HLA contributes only modestly to
overall susceptibility (18, 19).
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Within the areas of high prevalence there are second order patterns which are mainly due
to one or more environmental factors. An obvious trend is the increase in MS prevalence in
more temperate regions, the so-called north-south gradient (20). There are also smaller scale
trends which occur within the same general latitudinal zone. For example, in Canada, MS
prevalence in the outports of Newfoundland (~25) is an order of magnitude less than in the
rural areas of Alberta (~220) even though genetics and latitude are essentially the same (21,
22). These variations of MS prevalence in areas of genetic similarity are possibly explained
by differences in dietary habits with increased consumption of dairy, gluten and saturated
fat correlating with areas of higher MS prevalence (23, 24, 25, 26). The
Newfoundland/Alberta difference in prevalence demonstrates this dietary variance very
well with the fishing and vegetable patch food sources of the Newfoundland outports
contrasting with the cattle ranches and wheat farms of Alberta. Thus, the epidemiological
data are compatible with the hypothesis that Neolithic, agricultural foods play a role in MS
MS Pathogenesis
Currently the extensive MS pathogenic data base provides tight constraints on possible
causal factors and has led researchers to postulate that MS is an autoimmune disease caused
by activated T helper-cells which are reactive with one or more proteins in myelin in the
CNS. Such potentially autoantigenic proteins include myelin basic protein (MBP),
protolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), myelin associated
glycoprotein (MAG), heat shock proteins (HSP) and alpha -beta crystallin (27). Furthermore
it is most often interpreted that the autoreactive T -cells are activated in the periphery by
foreign antigens (27, 28). The two favoured mechanisms for such peripheral activation of
myelin sensitive T-cells are by superantigens and by molecular mimicry (27). Little evidence
has been offered for the role of superantigens but numerous studies have provided
supporting evidence for molecular mimicry to be an effective mechanism for precipitating
an autoimmune response (3, 4, 5, 6). For example, the recent Rand et al. study (29) identified
a specific IgG antibody which occurred in the CFS of MS patients and which was cross
reactive for both a common infectious agent (EBV) and a CNS autoantigen (alpha -beta
crystallin). As noted by the authors the odds of such a chance occurrence of a cross -reactive
antibody in a number of MS patients are so high that the likelihood of molecular mimicry
occurring in MS is very high. It still remains to be determined which foreign proteins may
be mimicking CNS proteins and how and when such foreign proteins engage the immune
system such that mimicking reactions may occur.
Current data indicate that numerous common viruses and bacteria have the potential to
mimic the immuno-dominant epitope of MBP which many favour as the most likely target
of autoaggressive T-cells (5, 6). Similar studies have not been done for the other common
myelin proteins in the CNS and thus many more potential mimics may exist.
If the hypothesis that agricultural food proteins are involved in MS pathogenesis is to be
taken seriously it must be demonstrated that such proteins can play one or more roles in
promoting and/or participating in molecular mimicry and other immunological reactions. A
variety of data indicate that the food proteins from dairy, gluten, yeast and legumes can
indeed be involved in the activation and expansion of autoreactive T -cells in at least four
1. Agricultural dietary staples such as cereal grains and legumes contain glycoproteins
called lectins (e.g. wheat germ agglutinin ¡WGA], phytohemagglutinin ¡PHA]). These
lectins can promote an overgrowth of gut bacteria such as Escherichia coli and
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Klebsiella which are potential mimics (11). Such overgrowth relates to autoimmunity
because it increases the number of potential mimics.
2. The lectins themselves can also result in substantially increased intestinal permeability
(12, 13). Such an increase in intestinal permeability results in the translation of
pathogenic viruses and bacteria to the periphery (30) where they can participate in
molecular mimicry and other immune responses. Such mimicry reactions may involve
three way cross reactions between viral antigens, myelin antigens and HLA antigens
similar to that hypothesized for rheumatoid arthritis (31, 32).
3. Additionally, dietary lectins from grains and legumes which escape into the periphery
have the ability to interact with components of the immune system in a manner which
can promote autoimmune reactions. Both WGA and PHA have been shown to rapidly
cross the gastro-intestinal barrier in a number of animal experiments (33, 34). PHA
has been demonstrated to promote the expansion of activiated T-cell lines (35), to
elevate ICAM expression (36, 37) and to stimulate the production of pro-inflammatory
cytokines such as IL-1 and TNF alpha (38, 39, 40). All of these actions would promote
previously initiated autoimmune reactions.
4. Finally, dietary antigens have the potential to participate in molecular mimicry of
autoantigens and infectious agents. Currently there has been no investigation of
molecular similarities between peptides derived from dairy, gluten and legumes with
myelin protein epitopes. However similarities between these food peptides and other
autoantigens involved in rheumatoid arthritis, uveitis and type 1 diabetes (7, 8, 9) as
well as infectious agents (EBV) (7) has been established. Thus it is plausible that food-
derived peptides also have the potential to mimic myelin protein epitopes.
The other aspect of diet which can affect immune reactions is the type and amount of fat
(41, 42, 43). Notably omega three essential fatty acids (EFAs) which are an important
component of Paleolithic nutrition (44), have been demonstrated to downregulate immune
responses (43, 45).
Thus dietary proteins from agricultural foods such as dairy, yeast, gluten and legumes
theoretically can play a significant role in the currently held model of MS pathogenesis.
Furthermore the replacement of omega three EFAs by agricultural -derived saturated fats
and omega six EFAs may well play a subsidiary role.
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