Need for Dietary Research into the Cause and Progression of Multiple Sclerosisby
Ashton F. Embry
here to visit Dr. Embry's website
This essay was submitted in January, 2000 to the Institute of Medicine (IOM)
Committee on Multiple Sclerosis: Current Status and Strategies for the Future
which was commissioned by the National Multiple Sclerosis Society (NMSS). The
purpose of the essay was to convince the Committee to include a recommendation
for research into the likely role that diet plays in MS onset and progression.
I am pleased that the IOM committee is taking such a wide-ranging look at
the current status of research into MS and strategies for future research efforts.
I would note the committee has an impressive line-up of experts although I think
that the committee would have been enhanced by at least one member from outside
the medical field (eg an expert on chaos theory). Also there is no one from the
client side of the fence, the inclusion of which might have also provided some
unique perspectives. I suppose the committee can consider this input as being
both from a scientist completely outside of medicine and also from a client.
have been a geological research scientist for over thirty years (click here for
details) and have worked mainly on large, multi-factoral problems such as the
origin of the Arctic Ocean and the occurrence and causes of global base level
changes. In 1995 my oldest child was diagnosed with MS and I have spent a great
deal of time since then reading the extensive MS literature with the goal of identifying
plausible causal factors of MS. In geology we accept the fact we can never know
anything with absolute certainty and we concentrate on the simplest solution(s)
which fit all available data. I have applied this same strategy to the epidemiological
and pathogenesis database for MS. I would note that I have nothing to gain and
all to lose from subjectively favouring one causal factor over another.
I would hope that the committee would unanimously agree
that both genetic and environmental factors play significant roles in MS. My main
interest is in the identification of the environmental factors and I believe this
is a very important area for future research. Given the current data base for
MS, I have concluded that the simplest (best) explanation for MS is that CNS autoaggressive
T cells are activated in the periphery by foreign antigens and that these effector
cells then cross the BBB and precipitate an autoimmune attack against one or more
autoantigens associated with myelin. I note that this is not the only plausible
cause for MS, just the one that best fits the data. Furthermore it is the one
which is seemingly favoured by most researchers at this time.
leaves important questions of what are the sources of the foreign antigens, how
do they activate the autoaggressive T cells, and when does this happen. Again
the simplest answers to these questions, given all the constraints of the data,
are 1) sources of foreign antigens are both infectious agents and food, 2) activation
of both naïve and memory Th cells is mainly by cross reactions induced by molecular
mimicry between foreign and self antigens, and 3) such activation happens throughout
the course of the disease in a chaotic fashion. I stress that all of these answers
are not proven or either widely accepted, they just seem to me to be the best
ones if all the data are honoured. I expect most members of the IOM committee
would agree somewhat with this analysis with the notable exception of my inclusion
of food being a source of foreign antigens which can result in the activation
of CNS autoaggressive T cells. The main reason for this submission to the IOM
committee is to expand on this concept and to argue for the need for research
which determines whether or not food-derived antigens play a substantial role
in MS onset and progression.
As stated earlier, I think most of the IOM committee,
and indeed most MS researchers, would agree that foreign antigens play a major
role in MS. So the question at hand is whether or not it is plausible that food-derived
antigens are part of the foreign antigen load which drives MS. My arguments for
why food antigens quite possibly play a role in MS are below. Once one accepts
that it is plausible (ie there is a reasonable chance) that food antigens contribute
to MS progression, then there can be no doubt that research is necessary to decide
the issue beyond a reasonable doubt. Furthermore, given the lack of industrial
incentives for doing such research (no significant financial reward), only charitable
and governmental organizations like NMSS and NIH can provide the necessary promotion
and funding for such research.
if it is found that food antigens do indeed play a role in MS onset and progression,
then that will revolutionize MS research and treatment. How many other proposed
research topics have that potential! So what is the circumstantial evidence that
indicates that food antigens may be a significant factor in MS?
of all, from a big picture view, it is reasonable to expect that food antigens
may play a role in a disease like MS which can be lumped with a large number of
chronic diseases in which both genetic and environmental factors play major roles.
Eaton and Konner (1985) published a very important paper in NEJM which introduced
the concept of Paleolithic nutrition. Simply stated, it argues that foods introduced
into the human diet by the agricultural revolution (~6000-8000 years ago for northern
Europeans) can potentially cause biochemical failures which lead to chronic illnesses
in genetically susceptible people because humans have not had time to genetically
adapt to such foods. Thus in a given population there will be a given percentage
of people who are genetically incompatible with one or more of the newly introduced
foods. These "new" foods include dairy products, grains, legumes and yeast as
well as large increases in the consumption of sugar, salt and saturated fat. The
pre-agricultural diet (Paleolithic diet) consisted of lean wild meat (low fat,
low % of saturates), fruits and vegetables. There can be no doubt that the newly
introduced foods have contribute substantially to other genetic-environmental
(chronic) diseases such as heart disease, hypertension, stroke, type 2 diabetes
and various forms of cancer. The question is do these new foods also contribute
to autoimmune diseases including MS. The evidence which indicates that these foods
do indeed play a role in autoimmune disease include:
geographic variations in the prevalence of autoimmune diseases tend to match variations
in food supply with higher prevalence occurring in areas where the new foods dominate
the diets (temperate climates). For example it was shown that the correlation
between milk consumption and MS prevalence was .84 (Malosse et al, 1992). Even
more impressive was the almost one for one correlation between type 1 diabetes
prevalence and consumption of a specific type of beta casein (.98!) (Elliott et
experiments show that foods such as milk, wheat and soy can precipitate IDDM and
RA in mice, rats and rabbits (Coombs and Oldham, 1981; Elliott et al,1984; Welsh
et al, 1985; Scott, 1996). Little has been done in this regard for MS although
I was recently in contact with Dr John Elliott of the University of Alberta who
told me that his recent experimental work has demonstrated that NOD mice fed an
elemental diet were resistant to MOG-induced EAE but lost that resistance when
milk protein was added to the diet (J Elliott, pers. comm., 1999).
with autoimmune diseases have T-cells and antibodies which cross react with both
self proteins and food proteins (Martin et al, 1991; Perez-Maceda et al, 1991;
Cheung et al, 1994; Ostenstad et al, 1995 ).
studies of proteins from wheat, milk, yeast and legumes show that they can have
very similar molecular structures as self proteins and that peptides derived from
food proteins activate autoreactive T-cells derived from people with autoimmune
disease ( Singh et al, 1989; Ostenstad et al, 1995; Cavello et al, 1996; Honeyman
et al, 1998).
trials with people with RA and Crohn’s disease, both organ-specific, cell-mediated
autoimmune diseases with numerous immunological similarities to MS, show that
avoidance of proteins from wheat, dairy and legumes results in major symptom improvement
(Panush et al, 1986; Darlington and Ramsey, 1992; Riordan et al,1993; Haugen et
al, 1994; Beattie and Walker-Smith, 1994; Husby et al, 1995; Kavanaghi et al,
1995; Fukuda et al, 1995; Zoli et al, 1997).
proteins from a variety of grains are the primary cause of two autoimmune diseases,
celiac disease and dermatitis herpetiformis (Marsh, 1992; Bodvarsson et al, 1993).
Also of note is that persons with celiac disease are much more susceptible to
other autoimmune diseases including RA, IDDM, autoimmune thyroid disease, Addison’s
disease and alopecia areata ( Lepore et al, 1996; Kaukinen et al, 1999).
me, when all this epidemiological, experimental, clinical and theoretical evidence
is considered as a whole, it is very reasonable to postulate that food proteins,
especially those recently introduced into the human diet, may well play a role
in a variety of autoimmune diseases including MS.
Agent-Diet Model for MS
Given this, it is still necessary to provide
a theoretically plausible pathogenesis for MS which involves food proteins and
there should be no major contradictions with the available epidemiological data
base. Below is a simple hypothesis for MS pathogenesis, which for the most part
follows the one currently favoured by most researchers. Essentially the addition
of food proteins is nothing more than a small, but potentially critical, modification
of this widely accepted model.
"infectious agent-diet model" for MS cause is as follows:
with one or more childhood illnesses (e.g. Epstein-Barr,HHV-6) results in an autoimmune
reaction against tissue in the CNS by molecular mimicry (Wucherpfennig and Strominger,
1995). Such autoimmune reactions are suppressed before any demyelination occurs.
However memory cells against the infectious agent are produced and such memory
cells can be seen as an autoimmune time bomb because they are also potentially
autoaggressive and are much more easily activated than naïve cells (Lovett-Racke
et al, 1998).
time, intestinal permeability increases due to various factors including food
allergies, alcohol consumption, candida overgrowth and non-steroidal anti-inflammatory
drugs (Doe et al, 1979). The consumption of gluten and legumes also increases
intestinal permeability through the action of lectins (glycoproteins) (Freed,
increased intestinal permeability, intact food proteins begin to escape the gut
as do gut bacteria products (Walker and Isselbacher, 1974; Gardner, 1988).These
antigens are likely presented mainly by B cells (non-professional APC) and precipitate
an autoimmune response by molecular mimicry of the childhood infectious agents
and/or self antigens in the CNS. Cordain (1999) has discussed such three way mimicry
in celiac disease and the results of both Singh et al, (1989) and Ostenstad et
al (1995) indicate that three way mimicry between antigens derived from self,
food and infectious agents is a plausible mechanism for the development of autoimmune
disease. Such cross-reactions result in the activation of the autoaggressive memory
cells which do not require co-stimulation. These initial, rather limited reactions
are most commonly successfully suppressed by a reasonably well functioning immune
system before any clinically detectable damage is done.
chronic activation of the autoaggressive memory cells by food and bacteria mimics
which are escaping through the intestine wall on a near daily basis (MS never
sleeps!), combined with major reactivation events precipitated by rare infections,
finally results in a failure of the suppressor side and a major autoimmune attack
occurs. This is eventually suppressed, and depending on the strength of the immune
system and its ability to suppress subsequent autoimmune reactions, the individual
experiences a benign course, a relapsing-remitting course (younger, healthier
immune system) or a progressive course (older, degraded immune system).
only difference between this model and the currently favoured model of infectious
agent-driven MS is the addition of food antigens which potentially cause small,
autoimmune reactions on an almost daily basis. Thus we may have two different
modes of autoimmune reactions occurring in MS, one small and frequent (food-driven)
and one large and rare (infectious agent-driven). Many geological processes (e.g.
erosion) have a similar duality in terms of magnitude and frequency and many debates
have been held on the relative importance of each type of action. Is the landscape
mainly shaped by almost imperceptible, day to day erosion or by the powerful 1000
year storm? It is now agreed that both processes play important roles in landscape
evolution. Of course for MS it is important at this time to establish if the high
frequency, low magnitude process of food-driven autoimmunity even exists and,
if it does, whether or not it is of any significance.
would further suggest that the addition of such food-driven reactions to the model
improves its compatibility with the epidemiology of MS. One of the nagging problems
with the infectious agent-driven model has been the fact that the geographic prevalence
differences for MS are not matched by differences in the prevalence of the various
infectious agents postulated to play a role in MS. The major differences in MS
prevalence in Australia (McLeod et al, 1994) are certainly not matched by notable
differences in infection types, rates or timing. Also it has been documented that
MS is more prevalent in inland farming communities than coastal fishing communities
when genetics and latitude are held constant and these significant differences
are especially difficult to rationalize with the infection-driven model. For example
MS prevalence in the outports of Newfoundland is 25/100000 (Pryse-Phillips, 1986)
whereas in the farming communities of Alberta it exceeds 200/100000 (Svenson et
al, 1994). With genetics and latitude being essentially the same for these two
areas of Canada, such a near ten fold difference cannot be easily explained by
the infectious hypothesis. However, with the addition of the food antigen factor,
which would take into account the dominance of high fat meats, dairy and grains
in the Albertans’ diet in contrast to the dominance of fish and vegetables of
the Newfoundlanders’ diet, this major difference in prevalence becomes much better
understood. This difference between farming and fishing communities has also been
documented in Norway (Swank et al, 1952) and in the islands north of the Scotland
(Shetlands vs Faroes) (Fog, 1966) and again the food antigen factor helps to explain
Given that dietary research is required for MS, the next
question is what type of research would effectively answer the question of whether
or not dietary proteins play an important role in MS. To me I think the best approach
would be one or more clinical trials with the subjects using a Paleolithic diet
as the therapy. Such a diet emphasizes lean meats, fruits and vegetables and excludes
dairy products, grains, yeast and legumes. Other features include a more balanced
ratio of fat types, a reduction in salt and sugar intake and no alcohol. The main
variable to be measured would be lesion load as determined by serial MRI scans
over a one to two year time period. I leave the details of such a trial to those
who are experienced in such matters but to me such clinical trials, if properly
designed and run, would decide the issue to most people’s satisfaction.
hope that the IOM Committee finds my reasoning compelling enough to recommend
research into food antigens and MS. This would constitute extraordinary research
(in the sense of Kuhn, 1970) which has been exceedingly rare in the MS research
agenda for the past decade (oral tolerance research being a notable exception)
(Weiner et al, 1994). There is no doubt we need the normal, inductive science
which has completely dominated MS research for decades. However, most breakthroughs
in science have not come linearly from such plateau science although such science
is absolutely necessary for novel concepts to be conceived in the first place.
The suggested dietary research is clearly not safe, predicable research which
commonly has little or no impact (most MS research papers are rarely if ever cited).
It is risky research which can potentially yield major returns for a relatively
In summary, I believe there are substantial data and theoretical considerations
which make the concept that food proteins play a role in MS progression a very
plausible hypothesis. As such, I think such a hypothesis should be tested as quickly
and thoroughly as possible with clinical trials being the best research method.
The MS research community rarely is presented with a plausible, testable hypothesis
for MS progression and it behooves the community and the main funding agencies
to act expediently in testing it. Of course those with MS, most of whom are consuming
the potentially problematic food proteins every day, would be most interested
to know beyond a reasonable doubt if their current dairy and grain-dominated diets
affect the progression of their MS or not. Right now no responsible researcher,
including all those on the IOM committee, can guarantee persons with MS that food
proteins from such foods as dairy and grains will not affect the progression of
their MS. In this atmosphere of uncertainty some persons with MS have even opted
for diet revision over use of one of the recommended drugs to try to slow MS progression.
I am sure most of the IOM Committee members would not support such an action but
until reliable information on diet and MS is available it is impossible to say
with confidence if such a choice will be detrimental or not.
all else, I think it is imperative that sufficient research be done as soon as
possible so that MS researchers and clinicians can provide persons with MS with
a definitive statement on the role of dietary proteins in MS. Statements such
as "we do not know" and "there is no definite proof that food proteins are involved
in MS" (an ambiguous way of saying we do not know) are not adequate and are potentially
harmful. I hope the IOM Committee will recommend that sufficient research be done
to finally settle this important question which continues to plague many persons
with MS and which could open up entirely new fields of research and therapy for
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