Magazine Columns

The following columns related to MS and diet were written by Ashton Embry.

• New Studies Show the MS Drugs Don’t Slow Progression
• CCSVI - A Huge Breakthrough in MS?
• A Tale of Two Trials
• The Need for Proper Regulation
• Vitamin D and MS – An Update
• Statistics and Risk Assessment
• Vitamin D Supplementation and Autoimmune Disease - Opposing Views
• The Role of Lectins from Grains and Legumes in the MS Disease
• Up from the Chair - The Terry Wahls Story
• Advice for the Newly Diagnosed
• Low Dose Naltrexone
• The Varied Roles of Infectious Agents in the Onset and Progression of MS
• Appraising Therapies
• Multiple Sclerosis and Food Proteins
• Drastic Measures for Aggressive MS
• Genetic Epidemiology and Causal Factors of MS
• Scientific Subjectivity
• The Three Stages of MS
• MS and Supplements
• MS and Fats – A Balancing Act
• Are patients being given objective information on MS drugs?
• MS and Vitamin D Deficiency
• MS and Vitamin D Supplementation
• Where Did MS Come From?
• MS and First Do No Harm
• Nutrition Factors and Multiple Sclerosis - Part I: Identifying the Prime Suspects
• Nutrition Factors and Multiple Sclerosis - Part II: Vitamin D
• Death and Dividends: The Tysabri Debacle

The Varied Roles of Infectious Agents in the Onset and Progression of MS

By Ashton Embry

Multiple sclerosis is the result of various environmental factors acting upon a genetically susceptible individual. There is not much that can be done about one’s genetic makeup. However, a person can either lower their risk of MS or can affect its course by changing their exposure level to the various environmental factors which drive the onset and progression of MS. Thus it is important to understand what environmental factors are involved in MS. In the past I have written mainly about the various nutritional factors which contribute to the MS disease process. These are the easiest factors to address when making changes to one’s lifestyle.

Another major environmental factor involved in MS encompasses varied infectious agents that include viruses, bacteria, parasites and fungi. It has become apparent that infectious agents play various roles in MS. MS was first recognized as a specific disease in the mid-part of the 19th century. At this same time it was discovered that infectious agents, mainly bacteria, were the main causes of many diseases. Thus, it was natural for early workers to assume MS was also an infectious disease caused by bacteria. Consequent attempts to identify the specific MS bacterium came up empty and in the early part of the 20th century it was proposed that MS was caused by a viral infection. Again, efforts to identify a specific infectious agent and to treat MS with anti-infection therapies were not successful.

By the late 1930s, the concept of autoimmunity became reasonably well established and the possibility that MS was an autoimmune disease was entertained. From 1940 to 1970, the concept of MS as an infectious disease was gradually supplanted by the view that MS is an autoimmune disease. Currently, the prevailing view strongly favours the autoimmune interpretation although a few researchers still regard MS as an infectious disease caused by a specific virus or bacterium.

Those who advocate that MS is an infectious disease suggest that MS is caused by either a latent virus which is periodically reactivated or a chronic viral infection. It seems every so often a research team announces they have “discovered” the infectious cause of MS and candidate agents have included HHV-6 (roseola), Varicella (chicken pox), Epstein-Barr (mononucleosis) and Chlamydia (a common bacterium), not to mention canine distemper virus, Lyme Disease bacteria and various retroviruses. Further work has disproved the causal role of all the proposed infectious agents but I am sure another one will be trumpeted as the cause of MS in the near future.

Overall, the evidence which supports the infectious hypothesis is rather weak. One strong piece of evidence against this concept is that no specific infectious agent has ever been consistently detected in MS lesions despite the use of extremely sophisticated techniques. An even stronger argument against an infectious cause is that immune suppressant drugs tend to improve the disease rather than make it worse. This latter point is especially convincing because, if infection was driving MS, immune suppression would allow the infectious agent to expand and do more damage. This does not happen. Thus I think we can confidently reject the hypothesis that MS is an infectious disease.

Just because it does not appear that MS is an infectious disease does not mean infectious agents do not play various roles in MS onset and progression. In most cases the MS disease process appears to begin in childhood. The simplest and most widely accepted explanation for the triggering event is that a common childhood infection such as roseola (HHV-6) or Epstein-Barr (EBV) infection sets MS in motion by resulting in cross reactions between viral antigens (protein pieces) and parts of a protein in myelin. Thus, when the immune system of a genetically susceptible person becomes sensitized to the EBV or HHV-6 antigen, it also becomes sensitized to myelin. At this time a pool of myelin-sensitive, memory, immune cells can potentially form. These cells represent a time bomb which detonates and drives MS in later life when the myelin-sensitive immune cells lead a substantial immune attack on myelin.

As has been discussed in past columns, it appears vitamin D is protective against MS and, that if a child has an adequate blood level of vitamin D, they will be protected from MS. The reason for this is that adequate vitamin D ensures that an infection with an MS-driving virus such as EBV or HHV-6, is well controlled and that a “time bomb” pool of myelin-sensitive, immune cells does not form. Thus MS-causing infections can be rendered toothless by ensuring that children have an adequate blood level of vitamin D (100 nmol/l) at all times. Unfortunately most children do not have an adequate level of vitamin D for at least part of the year and there is no indication that the public realizes the importance of adequate vitamin D supplementation for children.

There is also solid evidence that viral and bacterial infections can initiate exacerbations during the R-R phase of MS. This likely occurs because various infectious agents, including the flu, can activate myelin-sensitive immune cells through cross reactions. Another way infections can drive MS is that infections of the gut can result in increased intestinal permeability (“leaky gut”). This often leads to the passage of food and bacterial proteins across the gut wall. When such proteins meet the immune system, they can also activate myelin-sensitive immune cells. Finally, general infection can cause the release of various inflammatory mediators and these can also contribute to increased autoimmune reactions.

Infectious agents play another, even more surprising role in MS. It is apparent that people who have chronic, parasitic infections are protected against MS. Notably such parasitic infections were standard for everyone during the 4 million year history of human beings. It is only in the last 100 years that such chronic infections have been eradicated in developed countries, where, not by chance, the MS rate has exploded. The main way such parasites protect against MS is that the parasites induce the immune system to produce regulatory immune cells which in turn off the attack side of the immune system. This evolutionary bargain protects the parasite against the host’s immune system and benefits the host by preventing autoimmune disease. Currently, muted parasites are being tested as a therapy for Crohn’s Disease (another autoimmune disease) and are being considered for use in MS. Such a therapy may be quite effective.

In summary, infectious agents play a varied role in MS, from initiating the disease in the first place, to precipitating exacerbations, to potentially being a beneficial therapy. Adequate vitamin D can ensure that infections do not have a noticeable effect on MS progression and do not initiate the MS disease process in the first place.

back to top

Appraising Therapies

By Ashton Embry

There is certainly no shortage of proposed therapies for helping a person with MS control the progression of their disease. Most persons with MS are naturally very interested in hearing about as many therapeutic options as possible because right now there is no obvious therapy which will, beyond a reasonable doubt, stop MS in its tracks or even slow it significantly. With each new therapy option comes the big question “Should I give it a try or not”. In this column I will try to provide some advice on how to best answer this critical question.

Because MS can cause a great deal of damage in the central nervous system, it is important to do everything reasonably possible to ensure MS does not result in serious disabilities over the long run. We often look to physicians to prescribe an appropriate therapy to take care of a specific medical problem (e.g. an antibiotic in the case of a bacterial infection). Doctors like to use what they call “evidence-based” medicine to prescribe the appropriate therapy for a given ailment. Evidence-based medicine simply means that the recommended therapies are based on reliable scientific evidence.

To conventional medicine, “evidence” usually means the results of acceptable clinical trials (e.g. randomized, blinded trials with a large sample size) and other scientific evidence is rarely considered in decision making. This attitude can be seen in the oft quoted book “Therapeutic Claims in Multiple Sclerosis” published by the International Federation of Multiple Sclerosis Societies. Any proposed therapy for which there are no supporting clinical trial results is summarily dismissed. Such an approach to evidence-based medicine ensures that only patented drugs manufactured by pharmaceutical companies can be considered as a suitable therapy. Thus don’t expect a neurologist to recommend anything but a drug therapy. Such a narrow approach is not the best for appraising a variety of proposed therapies for MS and selecting those that might be of benefit.

First of all other scientific evidence such as epidemiological and animal experimental data can be very useful for reaching a solid decision about a therapy. Furthermore, other factors must be taken into account when evaluating the proposed therapy. These other factors include the financial cost of the therapy, its safety and its ease of use. Clearly, if a proposed therapy is low cost, safe and easy to use, one would not require much scientific evidence before giving it a try. It all comes down to a benefit/risk/hassle/finance analysis. If risk and hassle are very low and costs are reasonable then one has very little to lose and perhaps much to gain by using such a therapy regardless of the availability of much reliable science.

When it comes to a drug, there is no doubt that very reliable, clinical trial data are needed before such a therapy can be recommended. Drugs are very powerful chemicals and thus carry a high risk that negative side effects will outweigh and positive effects. Death can be one of the negative side effects as shown by the Tysabri trials of a few years ago. The currently recommended drugs, with the exception of Tysabri, have reliable clinical trial data which indicate they are reasonably safe and that there is a chance they will slow disease progression over the long term. This chance of some success tends to offset their high cost and unpleasant side effects.

Tysabri, despite the fact that it has been approved, is still under cloud of doubt regarding safety. A recent study showed extremely low T helper immune cells in the CNS of those using Tysabri. Notably, the counts were equivalent to those found in AIDS patients who do suffer from uncontrollable brain infections because of low T cell counts. In AIDS it is the virus that is responsible for such low numbers but with Tysabri it is the drug itself, which is causing such an alarming effect. Clearly more scientific evidence is needed before one could feel comfortable about using Tysabri.

A proposed nutritional therapy such as the “Best-Bet Diet” is safe, costs little and has potential positive side effects of better general health. However, it does represent a fair amount of hassle due to the drastic dietary changes required. In a case like this, one would want a reasonable amount of scientific evidence but, unlike for a drug, clinical trial data would not be essential due to the complete safety of the therapy. Importantly, a lot of diverse scientific evidence has been compiled to support use of the various aspects of the BBD and thus persons with MS would be wise to seriously contemplate its use.

Perhaps the hardest therapies to evaluate are those with no clinical trial data, have no solid scientific rationale, are quite expensive and/or are possibly harmful. A classic case of such a therapy is the use of “goat serum” which is also known as Aimspro. To me such a therapy is best avoided until a reasonable amount of scientific data are available regarding its safety and its effectiveness for MS. An additional factor worth looking at with such a therapy is the type of individual(s) promoting it. Are they health care professionals or are they businessmen looking to earn lots of money? A recent newspaper article revealed that the principal businessman behind Aimspro has a “spotty” track record when it comes to business (one or more bankruptcies) and that Aimspro is his first foray into health care. These are red flags which are additional reasons to avoid such a therapy until some proper scientific evidence is available. Notably, it is important to give “anecdotal accounts of success” little weight unless you are very familiar with the cases. It seems every therapy under the sun, no matter how implausible, always has lots of anecdotal accounts which attest to its great value.

In my next column I’ll be showing an example of an appraisal of a proposed therapy which was first recommended over 50 years ago and is now part of the BBD. This is the avoidance of specific food proteins such as gluten and dairy.

back to top

Multiple Sclerosis and Food Proteins

By Ashton Embry

The basic disease process of MS involves the activation of autoaggressive, myelin-sensitive, immune cells that subsequently lead an autoimmune attack on myelin in the central nervous system. This leads to myelin and nerve axon destruction and the occurrence of the many disabilities that characterize MS. The myelin-sensitive immune cells are activated by fragments of foreign proteins which closely resemble fragments of myelin proteins (“molecular mimicry”). The two obvious sources of foreign proteins are infectious agents and foods. There is little doubt that infectious agents are involved in MS but it is less known that there is substantial evidence that implicate food proteins in MS and other closely related autoimmune diseases.

This article summarizes the scientific evidence that suggests various food proteins may be playing a role in the activation of the autoaggressive immune cells. If this is indeed happening, then avoidance of those food proteins might well help to decrease the activation of myelin-sensitive immune cells and thus be of benefit for controlling MS.

Substantial scientific evidence points to proteins derived from dairy products as being involved in the MS disease process. An epidemiological study showed a very close correlation between the prevalence of MS in a country and the amount of milk consumed in that country. Subsequent immunological studies demonstrated that protein fragments from milk closely resemble parts of proteins associated with myelin. It was further demonstrated that these “mimicking” milk proteins can activate autoaggressive immune cells that are sensitive to myelin and that persons with MS carry much higher amounts of milk-sensitive T cells than do healthy controls. As a final part of this study, the researchers showed that injection of the milk protein into laboratory animals caused EAE, a disease which closely resembles MS. Thus it appears that milk proteins have the potential to activate autoaggressive immune cells that attack myelin. In another, yet to be published study, a researcher demonstrated that mice fed a diet with no proteins did not develop EAE despite being primed to do so. When milk was added to the diet of the mice, they developed EAE. It is also worth noting that diverse research including small clinical trials has implicated milk in closely related autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and Crohn’s.

Other sources of potentially problematic proteins are the grains wheat, rye and barley, all of which contain gluten, a complex mix of proteins. Gluten has been identified as the cause of two autoimmune diseases, celiac disease and dermatitis herpetiformis. It has also been implicated in neurological diseases including one called gluten ataxia. This establishes beyond a doubt that food proteins can play a substantial role in the onset and progression of autoimmune disease. The evidence linking gluten to MS is not strong. It has been noted that areas of high rates of MS coincide with areas of major gluten grain cultivation and consumption. An animal study found that mice on a gluten free diet had much less disability than those on a regular diet after EAE was induced. No studies have been done on determining if proteins in gluten grains are “molecular mimics” of myelin proteins so this question is still open. However it has been established that protein fragments from gluten grains closely resemble parts of self-proteins in the joints and pancreas. These grain-derived proteins can activate autoaggressive immune cells that are part of the disease process in rheumatoid arthritis or type 1 diabetes. Avoidance of gluten has been found to reduce symptoms in rheumatoid arthritis and Crohn’s. Another relevant study demonstrated that adding gluten to the diet of genetically susceptible mice caused the mice to develop type 1 diabetes.

The last food type that is suspected of contributing to autoimmune diseases such as MS, rheumatoid arthritis and type 1 diabetes is legumes (beans). Like gluten, legumes have been found to yield protein fragments that closely resemble self-proteins in the pancreas and in joints. Soy, a commonly consumed legume, can cause genetically susceptible mice to develop type 1 diabetes. No epidemiological or immunological studies have been done for legumes and MS.

In summary, dairy products, gluten grains and legumes have all been implicated in MS and/or closely related autoimmune diseases. Notably these food types are some of the most allergenic foods and this further demonstrates a general lack of compatibility between these food types and the human immune system. Such a lack of compatibility with the human genome is best explained by the fact that these foods have been added to the human diet relatively recently, during the agriculture revolution over the last 10,000 years. This may seem like a long time but it is extremely short when compared with four million years of human evolution. It is postulated that humans have not had sufficient time to adapt to such foods and that part of the population still carries genes that result in immune problems caused by these food types. Autoimmune reactions may well be one of the immune problems associated with these food types as evidenced by the data discussed above.

Many people with MS are choosing to avoid eating dairy products, gluten grains and legumes because they do not want to take the chance that such foods might be activating myelin-sensitive immune cells. Such a substantial change in dietary habits can be accommodated with a few strategies. Dairy products are the main source of calcium for many people and thus, if dairy products are not eaten, a calcium supplement of 1000 mg is essential. Rice products such as rice breads and pastas can readily be substituted for gluten grain products. Legumes tend to be a minor component of most people’s diet and increased vegetable intake readily compensates for any nutritional losses associated with legume avoidance.

Clearly at this stage of scientific knowledge we do not know for sure if milk products, gluten grains and legumes are contributing to the MS disease process by activating autoaggressive immune cells. All we can say is that there is a reasonable chance that they are. Each person with MS has to weigh the scientific evidence and decide whether or not to take a chance and eat such foods or to play it safe and avoid them until science decides the issue.

back to top

Drastic Measures for Aggressive MS

By Ashton Embry

The average age of persons diagnosed with multiple sclerosis is about 30 and most begin with the relapsing-remitting phase of the disease. In the relapsing-remitting phase, persons with MS often experience about one attack per year. Such attacks are associated with a significant increase in one or more symptoms which cause one or more impairments. For many the symptoms slowly resolve and the person returns to their previous state or to a slightly worse one. Overall, the accumulation of disability is very slow and for some is minor. About half of those with R-R MS eventually enter the secondary progressive phase of MS after about 15-20 years in the R-R phase.

Of course anyone diagnosed with MS wants to avoid the disease path described above and to basically halt progression when they have little to no disability. The current first-line drugs (Interferons, Copaxone) can perhaps increase the time between diagnosis and entering the SPMS phase but there is little evidence that the drugs halt the disease progression for most or even substantially change the final outcome. They simply delay the arrival of severe disability which is a plus. Many with MS use a drug and hope (gamble) that they are one of the lucky ones who do not end up with severe disability by their 60s.

Of course there are many people who are diagnosed and who take a much more proactive approach than simply taking a drug prescribed by their neurologist and hoping they get lucky. There are a number of complementary and alternative methods for treating MS and many of these are described and discussed on innumerable websites and in New Pathways. The seemingly most effective, non-drug therapy on the basis of the available scientific data and anecdotal accounts is the adoption of various nutritional strategies which are lumped together as the Best Bet Diet (http://www.ms-diet.org). For many a strict adherence to the BBD is enough to completely halt disease progression. Others have had success with a combination of the BBD and one of the first-line drugs. To me it has always made sense to first use the BBD as soon as possible following diagnosis and then to add a drug only if the BBD does not keep MS well controlled (no increase in disability score).

Unfortunately for some, neither the BBD nor a combination of the BBD plus a drug keeps MS well controlled. To me this signals that the person has an aggressive case of MS and that they are at very high risk for progressing to severe disability over a relatively short time period. People with aggressive MS can have 6 or more attacks a year. So the big question is “What should a person do if the BBD and a first-line drug do not keep MS well controlled and they continue to experience frequent attacks and increased disability?”.

To answer this, it is important to understand why a person would experience such an aggressive and relentless form of MS. As I have discussed in previous columns, MS is caused by the activation of myelin-sensitive immune cells and a failure of the regulatory side of the immune system to quickly and effectively suppress the immune attack on myelin in the central nervous system. For those who do not respond to the BBD and drug regimen, it would seem that their immune systems are very far out of equilibrium. For example a person’s regulatory side may be so weak or their attack side so strong that the BBD with the help of a drug cannot push their immune system back to equilibrium where the regulatory side keeps the attack side well controlled.

To me when a person is afflicted with such an aggressive form of MS, it is time for drastic action and the sooner the better. Drastic action means major medical intervention which halts the unrelenting attack of the immune system on the person’s CNS. To accomplish this, the pathogenic elements of the person’s immune system have to be nearly or completely wiped out. Neurologists are slowly coming to this realization but have always been reluctant to act until a person already has very substantial disability and is wheelchair-bound. To me this is much too late.

There are a number of drug therapies which I would classify as drastic action. Three of them involve the use of drugs developed to treat cancer and they are used to wipe out much of the immune system. These include the drugs Campath 1-H, Cyclophosphamide and Mitoxantrone. The long term use of such drugs puts the person at risk for major infections, including the one that killed patients in the Tysabri trial, and for cancer as well as for other serious side effects such as cardiac problems with Mitoxantrone. I don’t think this is the best way to go.

On the other side of the spectrum is a stem cell transplant which is a rather common therapy for leukemia (cancer of the immune system). This involves a complete destruction of the person’s immune system through chemotherapy and radiation and the regrowth of a new one from stem cells. Recently two people with aggressive R-R MS were given a stem cell transplant and two years later both had substantially less disability and no evidence of any disease activity. There is no doubt a stem cell transplant carries some risk but to me it is worth considering if one is experiencing an aggressive form of MS.

An even better therapy may be available for aggressive MS. Last year the results were published on an open trial in which 27 persons with uncontrollable, R-R MS were given five pulses of Mitoxantrone, a major immune suppressant, over 8 months with Copaxone introduced after the third pulse. All 27 participants have either substantially improved or remained stable over time periods up to 5 years.

So why is this treatment apparently so effective? To me the key is the regrowth of the immune system in an environment of Copaxone which is a mixture of amino acids which mimic parts of myelin protein. It is likely that as the immune system regenerates it becomes tolerant to the widely present Copaxone amino acids and thus becomes tolerant of parts of look-alike myelin proteins that are normally attacked in MS. Notably, this therapy carries less risks than a stem cell transplant and may well be more effective given the myelin tolerance aspect of the regenerated immune system.

So in answer to the question of what to do when one has an aggressive form of MS that cannot be controlled by standard drug and nutritional therapies, I would say ask your neurologist to consider the use of the combination Mitoxantrone/Copaxone therapy. I would further suggest that it be combined with the BBD to increase the chances of keeping the MS disease activity well controlled.

back to top

Genetic Epidemiology and Causal Factors of MS

By Ashton Embry

I have always been somewhat surprised at the low level of interest by the MS research community in identifying the causal factors of MS. It seems to me that the best path to finding effective treatments for MS lies in finding out what causes it in the first place. There certainly were no effective treatments for infectious diseases until science discovered that micro-organisms such as bacteria and viruses were the causal factors of such diseases. Sadly, I suspect one of the reasons why little effort is being made in this field is the widely accepted dictum of the pharmaceutical industry “There is no money in a cure!”

Another likely reason why causal factors are not hotly pursued is that the only experiment that could identify a causal factor beyond any doubt would be to expose a group of people to suspected causal factors and see if they get MS. For obvious reasons this is never going to happen. So, to get at causal factors, historical scientific methods have to be employed and these usually entail epidemiological work which most MS researchers have no interest in. Epidemiology entails finding out everything you can about people who already have MS. Things like where they live, where they were born, what they eat, what infections have they had, what % of a given population has MS, all can help ferret out causal factors.

The good news is that a few researchers are trying to get at the causal factors of MS and one of the leaders in this field is Dr George Ebers, the chair of the neurology department at Oxford. He came to Oxford after a distinguished career in Canada where he did, and continues to do, a lot of genetic epidemiology. Genetic epidemiology looks at the rates of MS in persons who are genetically related to persons with MS or who have had long, close contact with persons with MS when they were growing up. Such information can tell us a lot about the nature of the causal factors of MS.

The classic genetic epidemiology work has been to study MS in twins, both identical and fraternal. Twins of course share many environmental factors during childhood and adolescence and identical twins have the same genetic makeup whereas fraternal twins only share 50% of their genes. They found that, for identical twin pairs with at least one having MS, both twins have MS in about 30% of the sets. For fraternal twin sets, both have MS in only 4% of the sets. This finding leaves no doubt that genes play a major role in MS and that only genetically susceptible persons get MS. On the other hand these results also tell us that one or more environmental factors are involved because for most sets of identical twins in which one has MS, the other one doesn’t. If MS was purely genetic, when one identical twin had MS, the other would too.

Dr Ebers and his colleagues then asked the question whether or not environmental factors specific to a family were involved in MS. They answered this one by studying the rate of MS in adopted siblings of persons with MS. Such individuals would share the same family environmental influences but none of their genes. They found that adopted siblings had the same rate of MS as the general population in Canada and this strongly suggested that specific family environmental factors were not involved. The researchers also studied half siblings of persons with MS and this population included those who shared the same home with the person with MS when they were growing up and those who did not. It was found that both groups had the same rate of MS which was about half of that of full siblings. This confirmed the lack of specific family related environmental factors and supported the conclusion that environmental factors which affect the population at large are driving MS.

Such a robust conclusion is very helpful because there just are not that many factors which affect the population at large, result in a very similar rate of MS along a given latitude and can contribute to the initiation and progression of an autoimmune disease like MS. The obvious ones are common infectious agents which can activate autoimmune immune cells, common foods which can activate or suppress immune cell activity, sanitation which determines the overall exposure of the population to infectious agents and the consequent “education” of the immune system, and vitamin D supply from sunshine and/or fish which determines a person’s ability to adequately regulate an autoimmune response. Notably these are exactly the same factors which I identified though a deductive exercise using the principles of evolutionary biology in concert with the known disease mechanisms (i.e. activation and failed suppression of autoaggressive immune cells).

One recent genetic epidemiological study involved looking at identical twins at different latitudes and seeing if latitude influenced whether both or only one twin got MS. It was clear that sets of twins with both having MS were much more common in higher latitudes than in lower ones. This added more support to the concept that vitamin D supply is a major causal factor in MS.

The genetic epidemiological results from the identical twins also tell us that in Canada only about half of the people who are genetically susceptible to MS actually contract the disease. This comes from the result that 30% of identical twins both have MS. Thus, out of a group of 10 identical twin sets with at least one with MS (i.e. 20 genetically susceptible individuals), only 13 will have MS and 7 won’t. Of course there must be some identical twin sets that are susceptible to MS and neither have MS. This would bring the overall rate of MS in susceptible individuals down to about 50%.

This begs the question of, if the environmental factors are affecting the population as a whole, why don’t all susceptible people in that population get MS. The answer to this question lies in the timing of exposure to the causal factors. The best explanation of why at least half the susceptible individuals do not get MS is that at least one of the factors must vary greatly in time and likely interact with another factor which only acts over a short time interval. Thus it would take a coincidence of timing of the two factors to cause MS and it appears such coincidence happens about half the time in Canada. Of the above factors, the obvious ones that fulfill these requirements are vitamin D supply which is high in summer and low in winter in Canada (and Britain) and an initial infection with a cross reactive agent which occurs over a short interval of time.

Putting everything together it is hard to escape the interpretation that MS is caused by an infection with a cross reactive virus or bacterium in a child or adolescent with a low vitamin D level (most likely from October to May in Canada). The need for a coincidence of the two factors nicely explains the 50% rate for genetically susceptible persons getting MS in a high latitude country like Canada where vitamin D supply is low to negligible for at least 8 months. Of course the MS contraction rate will decrease with decreasing latitude and consequent higher vitamin D supply over more of the year. The longer most people are protected against MS by adequate vitamin D over a year, the lower the MS rate. Thus in low latitude areas (e.g. northern Australia) few genetically susceptible persons get MS.

Is such a causal scenario without doubt? No it is not, but it is solidly supported and makes complete sense of all the known data. It is by far the best explanation of the cause of MS. However I estimate it will be at least 10 to 20 years before most MS researchers and clinicians accept that MS is fundamentally a long latency, vitamin D deficiency disease. A few classic examples of the long time it takes conventional medicine to accept an obvious causal factor of a disease include lack of sun exposure causing rickets (100 years), gluten consumption causing celiac disease (40 years) and a bacterium causing ulcers (12 years).

It is not hard to understand such resistance. When the causal factors of a disease are correctly identified, current approaches to research and treatment must be radically altered. Most people, especially researchers and clinicians, will fight long and hard against anything that would precipitate that much stressful change in their careers. Such is the genetic nature of human beings.

back to top

Scientific Subjectivity

By Ashton Embry

Scientists like to portray themselves and their endeavours as being very objective and completely lacking in any personal prejudices when it comes to determining and analyzing data. It would be wonderful if this was so but unfortunately scientists are affected by the same human frailties as everyone else. Thus subjectivity, rather than cold, hard objectivity, often plays a big role in science. Scientists tend to have a lot in common with lawyers in that once they take a position they will emphasize the evidence that supports their hypothesis and ignore, or at best downplay, the evidence which favours an opposing hypothesis. Thus in science we often have two “camps” when it comes to a given scientific question just like we have a prosecutor and a defense attorney when it comes to a legal question. This is fundamentally the way science progresses with the two camps battling it out until one completely overpowers the other and the views of the victorious group assume the mantle of scientific “truth”.

Various scientific questions about multiple sclerosis have their two camps and a good example of this is the debate of whether or not nutritional factors play a significant role in MS onset and progression. As most readers know I am a warrior in this ongoing battle which pits the pillars of conventional medicine - MS researchers, neurologists, pharmaceutical companies, National MS charities - against the holistic medical practitioners, a few iconoclastic scientists and the odd small charity. This debate is greatly influenced by financial considerations with conventional medicine being bankrolled by the wealthy pharmaceutical companies. The conventional medicine “camp” pushes the exclusive use of expensive drugs despite their questionable effectiveness and safety. At the same time this group strongly discourages the use of nutritional strategies despite robust scientific evidence which supports their use.

Persons with multiple sclerosis are interested in scientific opinions when it comes to new, potentially beneficial therapies such as a drug or a supplement. The scientific literature is often thought of as the most reliable source of information and I certainly believe this. One problem with the scientific literature is that one has to be a scientist to be able to access, read and most importantly, appraise the information in the medical journals. Most people, including many MS scientists and neurologists read only the abstracts of articles or, more commonly, will read only a second or third hand summary of the main conclusions of an article. This has pitfalls.

I have recently come across two classic examples of how one could be led astray by author subjectivity if the entire research articles were not critically read. In the first example the researchers have focused on the benefits of one drug while ignoring the apparent worthlessness of another. In the other example they have ignored key data and emphasized a relatively minor finding in order to demonstrate that a nutritional factor is not potentially involved in MS.

A few months ago two papers which described the results of the clinical trials involving Tysabri were published. One paper provided the details of a trial in which one group of patients used Tysabri while the control group received a placebo. A second, closely related trial had one group on both Tysabri and Avonex with the control group receiving only Avonex. In both trials those using Tysabri did far better than the control groups did in terms of active lesions and rate of attacks. There is no doubt that the researchers were justified in claiming that Tysabri positively affected the MS disease process despite having rare fatal side effects.

Another finding of these two trials was that the results of those on Avonex (the control group in the Tysabri plus Avonex versus Avonex trial) were exactly the same as those in the placebo group in the Tysabri versus placebo trial. The results were as follows:

These results leave no doubt that the highly touted MS drug, Avonex, is no better than a placebo and thus is most likely of no value for MS. None of the researchers pointed out this very obvious result. Such an oversight is not surprising given that the researchers all received payments from the company that manufactures Avonex.

The other paper of interest presented the results of the use of a gluten-free diet for rats which were given an animal form of MS known as EAE. EAE is induced in rats by injecting them with myelin proteins mixed with bacteria. The results of this study are illustrated in the accompanying graph. The red line represents the changes in disability with time of those rats on a gluten-free diet. As can be seen, they suffered worse effects (score of 3) early in the disease (14 days after disease induction) than those consuming gluten (blue line, score 2.5). However, as also can be readily seen on the graph, by day 40 the gluten-free rats were doing much better on average (score of > 1) than those eating gluten (score 2). The researchers chose to emphasize the result that the gluten-free rats had worse symptoms early on and in the abstract they noted that a gluten-free approach “exacerbated the course” of the disease. They ignored the result that the gluten-free rats had much less disability at the end of the trial. The authors clearly did not want to see, or at least admit to, any possible benefits of a gluten-free approach to MS.

These two examples show the strong bias which exists in the MS scientific literature which strongly promotes drug therapy and denigrates the potential of nutritional therapies. Persons with MS must realize that there is often much more to scientific results than those mentioned in abstracts and by spokespersons for conventional medicine. The scientific process in medical research is sometimes corrupted by an overriding subjectivity which is primarily driven by financial gain. It is not easy to get the “whole story” but at least the Internet provides an outlet for other sides of the story. This is a vast improvement of the past situation where the word of conventional medicine went unquestioned.

back to top

The Three Stages of MS

By Ashton Embry

Many people think MS has two stages: relapsing remitting (R-R MS) and secondary progressive (SPMS). I see the MS disease process as having three distinct stages. The often ignored and perhaps most critical stage of MS, is the first one which can be called Pre-clinical MS (PCMS).

The MS disease process usually begins in early childhood and is most likely precipitated in a genetically susceptible child by a cross-reactive, viral infection in combination with a low vitamin D level (i.e. winter to early spring). The viral infection results in the activation of immune cells which are sensitized to both the virus and to a protein in myelin, the substance that coats the axons in the central nervous system. The occurrence of a low vitamin D level at this time ensures that the viral infection is not well controlled and this lack of control allows a substantial pool of memory immune cells to develop. These memory immune cells, which are sensitized to the myelin protein as well as the virus, are basically an MS time bomb that most often explodes 20 – 30 years later.

During the long Pre-clinical stage of MS various cross-reactive proteins from infectious agents and foods sporadically activate the myelin-sensitive memory cells especially during times when vitamin D levels are low. These immune cells cause minor inflammatory reactions in various areas of the brain but such inflammation is very diffuse and is not detectable with an MRI scan. The damage associated with these minor inflammatory autoimmune episodes does not cause any noticeable symptoms but even at this stage nerve axons are damaged and destroyed. With each activation, the pool of problematic memory cells expands and the next episode of autoimmunity is potentially more extensive and damaging. During the long Pre-Clinical stage the immune system is gradually altered such that autoimmunity becomes less well controlled and the potential for more substantial autoimmune reactions increases. . Eventually a triggering event such as a cross-reactive viral infection during a time of low vitamin D level will precipitate a large enough autoimmune attack that symptoms become very apparent and the person sees a neurologist. A second, clinically apparent attack plus the appearance of distinct lesions on an MRI scan, usually results in a diagnosis of MS. The second stage of MS consists of well-defined attacks separated by periods of remission (R-R MS). New symptoms and disabilities often appear during an attack and many resolve during the following remission as the regulatory side of the immune system regains control. However there is sometimes a small incremental increase in disability by the time the next attack happens. An MS attack is caused by greatly increased, poorly controlled inflammation in the brain due to amplified autoimmune activity. The inflammation is often focused in distinct lesions although diffuse inflammation also occurs in the brain. The swelling associated with the inflammation results in most of the new symptoms. The inflammatory action, besides causing demyelination, also damages the nerve axons themselves and this can result in long-term disability. The more frequent and extensive the autoimmune-driven inflammatory action, the greater the axon damage and the greater the long-term disability.

Inflammation is not the only disease process which is contributing to increased disability during the R-R stage. When the nerve axons are damaged and severed in the lesions and possibly elsewhere in the brain and spinal chord, they degenerate along their entire length. This degeneration of the axons is perhaps the main cause of long-term disability. Thus the R-R stage is characterized by episodes of focal inflammation and by slow, progressive degeneration of nerve axons. Considerable disability accumulates due to these processes, especially the latter one.

The third and final phase of MS is known as Secondary Progressive MS (SPMS). It is characterized by few if any distinct attacks and by an insidious, slow and steady increase in disability. All the damage that occurred to the demyelinated nerve axons during the first two stages results in a slow and continuous degeneration of the long axon strands. This means less and less nerve impulses from the brain reach the muscles they are destined for and this translates into increased disability. Autoimmune inflammation continues during this time but is much more diffuse.

The long MS disease process which can essentially last a lifetime starts with low level inflammation, progresses to greatly increased inflammation and associated nerve axon degeneration and ends with continual nerve axon degeneration. Most of the accumulated disability is due to the degeneration component of the disease process. To avoid reaching the phase of steady degeneration and experiencing a downward spiral into serious disability, one must shut off the inflammatory process as early as possible. The ideal would be for susceptible persons to use a few nutritional strategies such as adequate vitamin D in childhood. However few do this because most believe that MS will never affect them.

More rigorous nutritional strategies and perhaps even one of the MS drugs are needed once MS is diagnosed. The sooner they are instituted the better the chance to short circuit the disease process and the appearance of long-term disability. Because many people do not experience serious symptoms in the early years of R-R MS they often do nothing and falsely believe that MS is no big deal. They do not realize that the disease process and associated damage are continuing. A major attack 5 –10 years after diagnosis interval often results in disabilities which do not resolve. Suddenly they want to “do something” about their MS. Nutrition can still be very helpful at this time but because of the extent of inflammatory damage and ongoing degeneration, the chances of returning to a disability-free state are low.

Once one is in the SPMS stage it is critical to use the nutritional strategies and to have a good exercise program with associated mind concentration. The goal of such a program is to “rewire” the brain and have nerve impulses use new routes and thus restore abilities. Again the chances of halting disease progression at this time are low because of widespread degeneration of the axons.

Overall it is important to understand the stages in the evolution of the MS disease process, why disabilities occur and accumulate and what strategies are needed to try to counter the processes going on in each stage. The main lesson learned from this is that the sooner one starts using nutritional strategies the better the chances of halting disease progression and avoiding any problematic disabilities. It would be wonderful if every child was given adequate vitamin D from birth onward. MS would become a very rare disease if this was done.

back to top

MS and Supplements

By Ashton Embry

The human body is best seen as a biochemical machine. For this machine to work at its best, many specific nutrients are needed in the proper amounts. This includes various proteins, fats, carbohydrates, minerals, vitamins and phytochemicals.

Long term, substantial deviations from the required nutrient intake usually result in one or more biochemical failures that we label as diseases.

An example of such a biochemical failure, due primarily to a long-term deficiency in vitamin D, is the loss of immune regulation such that an autoimmune attack on the central nervous system occurs. When consequent neurological symptoms become apparent, we call such a biochemical failure multiple sclerosis.

Supplements of Value in MS

A number of nutritional strategies known as the Best Bet Diet are recommended for MS with the goal of slowing or even halting MS progression by restoring biochemical equilibrium. An important part of such strategies is the use of a variety of supplements.

It seems there is an endless list of possible supplements for MS and a day hardly goes by without someone recommending yet another supplement which has had “amazing” results.

There is no doubt it is hard for anyone with MS to decide on a supplement regime that will be most effective while at the same time being reasonably priced.

The main questions seem to be “what supplements are needed?” and “how much of each is optimal?” Other issues include the cost of supplements, where they are best obtained and when they should be taken.

My approach to compiling a supplement list is the same as it is for deciding on any therapeutic approach to MS – I weigh all the scientific evidence to determine if a given supplement has a reasonable chance of being of value.

The main attribute I look for is whether or not the supplement can positively affect the MS disease process mainly through the suppression of autoimmune reactions. The other important role of supplements is to ensure there are no deficiencies of essential nutrients.

The recommended supplements are vitamins, minerals and a few more specialized items, most of which can be easily obtained at a reasonable cost. Suggested amounts for these are found both on the Best Bet Diet pages on the MSRC site and on the Supplements Page of this site.

There is no magic list but I think over the years a basic list has emerged. This can then be modified and added to according to one’s specific situation.

I would stress that supplements are not like drugs and that it can sometimes take months before the positive benefits are felt.

The Most Important Supplements

The most important supplements for MS are vitamin D, omega 3 essential fatty acids, calcium/ magnesium and antioxidants. Other basic supplements that are worth using are a probiotic, all the B vitamins, and the minerals zinc, copper and manganese.

Vitamin D

Anyone with MS or at high risk of getting MS would be wise to take 4000 IU of vitamin D3 a day as well as a fish oil supplement which contains at least 3-4 g of EPA + DHA. These amounts are a daily average. If you wanted to take 28,000 IU of vitamin D3 once a week the result would be exactly the same. It seems fish oils supplements are readily obtained, but unfortunately pills with a reasonable amount of vitamin D3 are not so easily found, especially in Europe where the maximum dosage per pill is 400 IU. I would emphasize that adequate vitamin D cannot be obtained from fish oil sources due to high amounts of vitamin A associated with such products. 1000 IU vitamin D3 pills can be bought at a reasonable price from American supplement companies on the Internet and I would recommend using such a product. Just type vitamin D and purchase into Google.

Calcium & Magnesium

Because it is essential that dairy products be avoided, an adequate calcium and magnesium supplement is also extremely important. These are found in most stores that sell supplements. Daily dosages of 800 – 1200 mg of calcium and half that amount of magnesium are sufficient.

Antioxidants

Another important category of supplements is antioxidants. There is ample evidence that people with MS tend to be deficient in antioxidants especially during an attack. Antioxidants play a significant role in regulating immune reactions so people with MS want to ensure they consume an overabundance of anti-oxidants through eating lots of fruits and vegetables and using a variety of antioxidant supplements.

Low cost, readily obtainable antioxidants include vitamin C, vitamin E, vitamin A and selenium. It is important to always make sure that these and other supplements do not contain any dairy or gluten fillers. Higher cost, more specialised antioxidants include grape seed extract, alpha lipoic acid, coenzyme Q-10, green tea extract and ginkgo biloba. Given the higher cost and greater difficulty in obtaining these, I recommend using one or two of these.

An even harder choice is whether or not to use inosine, a substance which is currently being tested as a treatment for MS. Inosine raises uric acid level and it is established that uric acid is a powerful antioxidant especially for neutralising perioxinitrite that causes damage in MS. An inosine supplement is fairly costly and also may result in gout. Thus there is no easy answer on its usage at this time.

Probiotics, B Vitamins, Zinc, Copper & Manganese

Other basic supplements that are worth using are a probiotic such as acidophilus, all the B vitamins in a B-50 pill and some minerals such as zinc, copper and manganese. These supplements are mainly for ensuring no deficiencies but also have some beneficial effect on the MS disease process.

Avoid Over-Priced and Over-Hyped Products

I am not a fan of any product that is sold by individuals in pyramid-selling schemes. These products in general tend to be overpriced and of questionable value. For example one such specialized supplement that is currently being flogged this way consists mainly of dairy (whey) protein and is potentially very harmful because of potential autoimmune cross-reactions. I would also caution against any special supplement that is touted, through anecdotal stories, to work miracles with a variety of diseases. To me, the recommended supplements are rather straightforward and do not include any exotic or miraculous products.

New Supplements – Glucosamine

Finally, it is always worth watching for a new recommendation for a supplement. Such an addition to the list is usually the result of recent research. For example glucosamine has recently been found to be very beneficial for EAE, the experimental version of MS. Is it worth adding glucosamine to your supplement regimen? I would say if your current nutritional strategies are not 100% effective then perhaps give glucosamine (1500 mg/d) a 6-month trial.

back to top

MS and Fats – A Balancing Act

By Ashton Embry

The Swank Research & Diet

The role of fats in MS has been passionately debated for over 50 years. It all began over 50 years ago when Dr. Roy Swank published a paper in 1950 claiming that saturated fat was an important factor in MS. Saturated fat is one of four main types of fat which also include monounsaturated fat, omega 3 polyunsaturated fatty acids (PUFA) and omega 6 PUFA. Swank supported his thesis with observations that populations that consumed high amounts of saturated fat had the highest rates of MS. He documented that farm-dwelling, meat-eating Norwegians had two to three times the rate of MS compared to their coastal, fish-eating cousins. Swank hypothesized that saturated fat caused MS by forming micro-emboli in capillaries in the brain and these resulted in CNS tissue degeneration.

Swank conducted a 40-year clinical trial to test the effectiveness of a “low fat” diet for MS. Swank uses the term “fat” only for saturated fat and he refers to the three unsaturated fat types as “oils”. He advised trial participants to eat less than 20 g of saturated fat a day and to increase their oil consumption, including the use of a cod liver oil supplement. Some of the participants did not follow the advice and consumed much more saturated fat. They became the “controls” for the study. The persons eating the low saturated fat/increased oils diet did much better than those who did not. They had much less disease progression and much longer life spans. Based on these results, a low saturated fat diet has been recommended for persons for MS in many self help books and even a few neurologists quietly suggest such a regimen.

The Role of Polyunsaturated Fats in MS

In the 1970s there was great interest in the possible value of increased polyunsaturated fats for MS and a few small clinical trials were done using either omega 6 PUFA (mainly sunflower oil) or omega 3 PUFA (mainly fish oil). These trials were inconclusive and the medical community lost interest in the role of fats in MS and their potential use as therapeutic agents. Over the past 30 years there have been a few epidemiological studies that suggest that fats may indeed play a role in MS, although an analysis of the huge Nurses database by Harvard scientists did not indicate any relationship between fat intake and MS occurrence.

Types of Fat & Immune Response

So do one or more fat types play a role in MS? MS is an inflammatory, autoimmune disease in which myelin-sensitive immune cells are inappropriately activated and are not sufficiently suppressed to prevent damage to myelin. Importantly, it has been demonstrated that the various types of fat have different influences on immune cells by either promoting or suppressing inflammatory immune reactions. This indicates that fats certainly have the potential to be involved in MS. The research shows that both omega 6 and omega 3 PUFA regulate the immune system and affect both the inflammatory side and the suppressor side.

Omega 6 PUFA (found in mainly in vegetable oils) tend to have more effect on the inflammatory side than do omega 3 PUFA. However one omega 6 fatty acid found in evening primrose oil and some other oils such as borage and blackcurrant – gamma linolenic acid – gets around this problem by starting later on in the conversion process of fatty acids and is therefore not pro-inflammatory.

Omega 3 PUFA found mainly in fish oil and a few other sources (flax, canola) have much more anti-inflammatory capability than do omega 6 PUFA. Thus the ratio of omega 6 to omega 3 consumed influences one’s anti-inflammatory response. Curiously there are no data to indicate that saturated fats have any noticeable effect on the immune system. Finally, monounsaturated fats (e.g. olive oil) are mildly anti-inflammatory.

Proportions of Fats Eaten Today

As discussed in my last column, the nutritional factors involved in MS are those that have been introduced into the human environment through the agricultural, industrial and technological revolutions. Although the overall amount of fat consumed has not changed very much, the proportions of the four main fat types being consumed in the developed Western world today are very different from those consumed by our Paleolithic ancestors. These societies eat much more omega 6 PUFA and saturated fat and much less omega 3 and monounsaturated fat. Notably some of the omega 6 PUFA in many baked products has been chemically changed to trans fatty acids that may also contribute to inflammation. Such a significant change in fat intake decreases a person’s anti-inflammatory responses and this contributes to the promotion of inflammatory diseases such as MS.

Ratios of Types of Fats

Given the above, it is very likely that fats play a role in MS onset and progression by decreasing anti-inflammatory capacity. Persons with MS or anyone wanting to lower their risk of MS would be wise to adopt the fat intake ratios of the Paleolithic. The most important ratio seems to be omega 6 / omega 3 which is currently estimated to be 10 –20. This starkly contrasts with the much lower Paleolithic ratio of 1-2. The Paleolithic ratio for monounsaturated/ saturated was 2-3 which is higher than that of today (>1).

Given these ratios, more omega 3 PUFA and monounsaturated fat and less omega 6 and saturated fat are required. 70 to 80 grams of total fat (720 kilocalories/ 35% total energy) is a reasonable daily intake. To achieve a proper balance of fat types the suggested amounts of the four fat types are

• 40g of monounsaturated fat
• 18 g of saturated fat
• 14 g of omega 6 PUFA
• 8g of omega 3 PUFA (mainly from fish oil)
• Trans fats, a product of the recent technological revolution, should be completely avoided.

With this understanding, it appears the main problem with a high intake of saturated fat for MS is that it tends to preclude an adequate intake of omega 3 PUFA and monounsaturated fat. Also, PUFAs compete and lose against saturated fat in the metabolic process. Swank’s recommendations of reducing saturated fat and increasing the oils had a beneficial effect because they led to a reasonable approximation of a Paleolithic balance of fat types and this in turn decreased inflammatory reactions. He was right for the wrong reason.

back to top

Are Patients Being Given Objective Information On MS Drugs?

By Ashton Embry

One of the hardest decisions for a person newly diagnosed with MS is to decide whether or not to use one of the available MS drugs (Copaxone, Avonex, Betaseron, Rebif) and if so, which one.

This dilemma is complicated by the fact that the main sources of information on the drugs (national MS societies, neurologists, MS nurses) usually supply only one-sided information on the drugs. This highly subjective information comes from published scientific articles on the results of the clinical trials that tested the drugs.

One might expect that such scientific articles would be very objective but unfortunately this is not the case. These articles are written by researchers who are funded by the drug companies that produce the drugs they are writing about.

Giving The Data Spin

It is not hard to understand that the authors of such articles do not bite the hand that very generously feeds them and thus “spin” the data in such a way that it is concluded that the drugs are very helpful for persons with MS. The drug companies then take these published, very subjective conclusions and spin them some more so that the drugs look even better.

The information providers seem only too happy to go along with the very biased conclusions published in the articles and supplied by the drug companies. They simply repeat the tainted and highly suspect conclusions like a mantra.

Thus persons with MS have little hope of making good decisions when it comes to the drugs because they do not have any solid, reliable information to base them on.

This serious conflict of interest problem is well recognised by the medical profession and, to counter it, an international organisation, known as the Cochrane Collaboration (http://www.cochrane.org), was set up in 1992. The main aim of this organisation is to “help people make well-informed decisions about healthcare by preparing, maintaining and promoting the accessibility of up-to-date systematic reviews of the effects of healthcare interventions”.

The Collaboration encompasses an established network of 50 research groups worldwide that prepares and maintains Cochrane Reviews, covering a range of medical specialties and free from the influence of drug companies. Approximately 10,000 people are actively involved in the work of The Cochrane Collaboration, almost all on a voluntary basis.

An Objective Look At MS Drugs

The good news is that the Cochrane Collaboration has taken an objective look at the MS drugs and produced Cochrane Reviews for them. The bad news is that the national MS societies and many neurologists and MS nurses are ignoring the results of these objective reviews and most people with MS are not being given this unbiased information on the MS drugs.

One Cochrane Review panel looked at all the clinical trial data for Copaxone, also known as glatiramer acetate, and this report is available in the Cochrane Library (http://www.nicsl.com.au/cochrane/index.asp).

An article on the main conclusions of this important study was published in November 2004 in The Lancet*, a very prestigious medical journal. The summary conclusion of the article is “Our systematic review of all randomised controlled trials of glatiramer acetate found little support for use of this drug in patients with MS”.

Other statements include “Whatever the disease course, glatiramer acetate is no better than placebo in preventing clinical progression at two years”, “When pooled estimates of treatment effect are adjusted for heterogeneity across studies, there is no difference between relapse rates for patients taking glatiramer acetate compared with those taking placebo up to two years” and “The median time to first relapse has also been studied, and no significant difference was shown between the treatment and control groups”.

I would emphasise that this review is based on a very objective analysis of the data and is not coloured by the financial influence of a drug company. The authors simply wanted to see if Copaxone helped or not and the available data clearly says it does not.

The Cochrane Collaboration has also undertaken an objective, systematic review of all the clinical trial data for the interferon drugs, Avonex, Betaseron and Rebif, for relapsing remitting MS. This review is also available at the Cochrane Library and a summary article was published in February 2003 in The Lancet.

The main conclusion of this study is “There is still a lack of solid evidence that recombinant interferons are effective after a year of treatment for patients with relapsing multiple sclerosis”.

Other conclusions include “Interferon seemed to reduce the number of patients who had exacerbations by about 25% during the first year of treatment but, at two years the results were not robust and were difficult to interpret because of the many dropouts” and “Doubts remain as to whether they can really prevent progression of the disease”.

Such conclusions are not exactly a glowing endorsement of the interferon drugs and are a far cry from the information that persons with MS most often receive. Finally the authors also note that “side-effects were common, and acute toxic effects adversely affected patients’ quality of life”.

Not surprisingly, this unbiased article on the interferon drugs drew heavy fire from the MS researchers who are well funded by the drug companies. In a series of discussions and replies published in The Lancet, the Cochrane Group, which included some very high profile and well respected MS researchers such as the chair of the Clinical Neurosciences Department at Oxford University, easily answered these desperate attempts to discredit the study.

The Cochrane Group was also able to make a few more damaging points such as the “unavailability of primary data”, “the sponsors’ analyses eliminate considerable patient experience from each calculation”, and “We had to extract key data, known to the investigators but not present in their publications, in order to arrive at this conclusion, which we find an unwelcome development”. This last statement comes as close as they dared to calling the authors of the original papers unethical scientists.

MS Patients Given Erroneous Data on Drugs

The bottom line is that a sober, objective look at the available data on the effectiveness of the MS drugs indicates that there is very little evidence that the interferons do much good and that there is no evidence at all that Copaxone has any value.

This is not to say that future proper studies and honest presentations of them may one day show these drugs have some value. It is just that right now such evidence does not exist.

To me it is a very sad situation that persons with MS continue to be given misleading and erroneous data on the drugs. It is quite possible that persons with MS are being sold worthless products that have nasty side effects.

It is difficult for persons with MS to obtain unbiased information on the MS drugs. However, it can be done and it is most important to do so. I invite anyone interested in objective information on the MS drugs to read the Cochrane Reviews and to draw their own conclusions.

Just like when one is buying a used car, there is no doubt it is “Caveat Emptor” (Buyer Beware) when deciding to use an MS drug or not.

back to top

MS and Vitamin D Deficiency

Recently a team of researchers from Canada and Britain led by Dr George Ebers of Oxford University published an important paper which provided evidence that persons born in the spring and early summer (April to July) were more likely to contract MS than those born in late fall and early winter (October to January). The authors suggested that this result may well be due to the supply of vitamin D the unborn child receives from their mother during the second and/or third trimester of pregnancy. In relatively high latitude areas such as Canada and Britain, most people’s circulating vitamin D is at a relatively low level in winter and thus the unborn child can potentially receive less vitamin D than is required for proper development. This deficiency does not happen when the latter stages of pregnancy occur in the summer and early fall when most people’s circulating vitamin D level is substantially higher.

This research has added further evidence that vitamin D supply plays a critical role in the onset and progression of MS. Such a relationship between MS and vitamin D was proposed 30 years ago but was completely ignored for almost 20 years. Recently a great deal of diverse evidence that links vitamin D supply to MS has accumulated and it now seems reasonable to classify MS as a long latency vitamin D deficiency disease. The most convincing evidence for this comes from the large variations in the rate of MS in Australia. Only 11 persons per 100,000 have MS in tropical Australia whereas MS is seven times more common (75/100,000) in temperate Australia. Intermediate values occur between these two extremes. It was shown that the varying rate of MS in Australia correlates very closely with the changing supply of vitamin D derived from ultraviolet radiation. Notably MS was more closely related to changing amounts of ultraviolet radiation than was melanoma skin cancer – a disease which is widely accepted to be mainly caused by exposure to ultraviolet radiation.

The Australian data indicate that 85% or persons in tropical Australia who would have otherwise contracted MS if they had resided in higher latitude, temperate areas escaped MS simply because they had an adequate vitamin D supply all year around. Thus, although there are other causal factors of MS such as various infectious agents and food proteins, adequate vitamin D throughout childhood prevents MS from developing in most cases regardless of exposure to these other factors. No vitamin D deficiency – no MS. This is why MS is best regarded as a long latency vitamin D deficiency disease.

Rickets is another vitamin D deficiency disease and it is characterized by poor bone development in children. Over much of the nineteenth century and the first two decades of the 20th century, many people ensured their children got adequate exposure to sunshine or got a daily dose of cod liver oil to prevent rickets. Such “folk remedies” were dismissed by convention medicine throughout this 100 year period despite the existence of a number of scientific studies which strongly linked rickets to sunlight supply. Eventually the evidence became so overwhelming that rickets was finally “officially” recognized as a vitamin D deficiency disease in the 1920s. Before this long overdue designation of rickets as a vitamin D deficiency disease, tens of thousands of children needlessly experienced great suffering. Will MS share the same fate as rickets by having the obvious relationship between vitamin D and MS ignored by medical doctors for the next 20 to 50 years? Such a scenario is not impossible and I expect it will be a many years before conventional medicine and associated organizations such as national MS societies refer to MS as a vitamin D deficiency disease. For some reason conventional medicine has a very hard time seeing the forest and taking appropriate action. I suspect it is a result of their basic philosophical approach to disease, which is to treat symptoms rather than determine cause.

The most important result of the realization that MS is a vitamin D deficiency disease is that an adequate intake of vitamin D by children can prevent MS. Thus just as modest vitamin D supplementation which is promoted by public health programs has made rickets an extremely rare disease, optimal vitamin D supplementation has the potential to essentially make MS a disease of the past. Between now and the time when such a vitamin D supplementation program is implemented, we will have the same situation that existed in the 1800s and early 1900s. Some people will have the wisdom to ignore official recommendations for vitamin D intake and use a common sense supplementation level just like the families who used folk remedies to prevent rickets 100 years ago. Many others will unfortunately blindly accept recommendations of woefully inadequate supplementation and some will pay a substantial price for choosing this thoughtless path.

In my column in the next issue of New Pathways I will discuss what constitutes an optimal vitamin D status and how one may best achieve it. I will also look at why vitamin D supplementation is important not only for preventing MS but also for people who already have MS.

Carpe D (Seize the Vitamin D).

back to top

MS and Vitamin D Supplementation

In my last column I explained why MS is best seen as a long latency vitamin D deficiency disease based on abundant and diverse scientific evidence. The current data strongly support the concept that an adequate supply of vitamin D throughout childhood and later life is protective against MS despite exposure to other environmental factors involved in MS. There is also evidence that an adequate supply of vitamin D can help slow the progression of MS for those who already have the disease. In this column I want to focus on how much vitamin D is needed to prevent or treat MS.

To understand how vitamin D can provide protection against MS and how much is needed, it is important to understand the basics of how vitamin D works in the body. When vitamin D is produced in the skin by the action of ultraviolet light or is taken orally in a food or a supplement, it is transported to the liver where it is transformed into a substance called 25 hydroxyvitamin D or more simply, circulating vitamin D. This substance circulates in the blood and is used by cells throughout the body to produce an active hormone that is often referred to as vitamin D hormone. This hormone has a powerful effect on cells and adequate vitamin D hormone is needed for proper cell functioning.

Notably immune cells need adequate vitamin D hormone for proper immune regulation. This regulation ensures that immune responses are appropriate and do not cause uncontrolled damage to self-tissue. Such uncontrolled immune damage to self is known as autoimmune disease when the damage becomes clinically apparent. When such damage occurs to myelin in the central nervous system the disease is labeled as multiple sclerosis.

With this understanding we can ask two critical questions in regards to preventing MS:

1. “What level of circulating vitamin D must one maintain from childhood onward such that the immune cells will function properly and not allow MS to develop.”
2. “How much vitamin D is needed from sun exposure, food and supplements to achieve and maintain such an optimal and protective level of circulating vitamin D”

Lately there have been a number of scientific papers that have addressed these questions.
It appears that an optimal level of circulating vitamin D is between 100 and 150 nmol/l (nanomols per litre). This has been determined by various observations. First of all people who live in low latitude sunny climates where MS is rare and have reasonable sun exposure have such a level of circulating vitamin D. Also it has been found that this level is protective against osteoporosis. Given that humans evolved in a low latitude, sunny climate with lots of sun exposure, it seems reasonable that such a level is what our genes need for optimal health.

The most important question for preventing MS is how much vitamin D is needed from the sun and oral sources to ensure one’s circulating vitamin D level remains in the optimal range of 100- 150 nmol/l. There have been a number of clinical trials in which the subjects were given varying amounts of vitamin D over 6 months and their resulting circulating vitamin D levels were measured. From this work it has been estimated that an intake of 4000-5000 IU each day will result in an optimal circulating vitamin D level. However it is important to note that these studies were done in the winter months when no vitamin D was obtained from sun exposure. Thus the amount of vitamin D supplement needed will depend an individual’s lifestyle and genetic response to vitamin D intake. Furthermore the amount needed by each person will vary during the year with more needed during the winter when little vitamin D is available from sun exposure. Finally the amount needed by babies and small children to achieve a protective level of circulating vitamin D will be less than that for adults. Clearly it is impossible to recommend a single supplement amount of vitamin D that will meet everyone’s needs.

For babies a supplement of 1000 IU all year around appears to be sufficient. For children 3 to 10 years of age, a 2000 IU supplement all year around will be adequate. For adults a 4000 IU supplement during the winter and a 1000-3000 IU supplement depending on sun exposure during the summer is likely adequate. To ensure one’s vitamin D supplement is resulting in an optimal level of circulating vitamin D, it is best to have one’s level of circulating vitamin D checked once or twice a year (fall and/or spring). One’s supplement regimen can be adjusted according to the test result as shown on the table below.

Finally what are the best sources of supplemental vitamin D? The easiest source is 1000 IU vitamin D pills that can be bought at a pharmacy or over the Internet. Cod liver oil can also provide some vitamin D but only up to 1500 IU can be gotten from such a source because of the associated high vitamin A content. I personally use a combination of cod liver oil and 1000 IU pills to provide 4500 IU a day.

In summary it is most important that everyone maintain a circulating vitamin D level of 100-150 nmol/l all year around to either treat MS or prevent it in the first place. For adults, a supplement in the range of 4000 IU/d should result in such a protective circulating vitamin D level but periodic checks of the one’s level are needed to ensure one’s supplement regimen is optimal.

back to top

Where Did MS Come From?

As part of my MS literature research I have tried to answer big questions such as “what causes MS?” and “where did MS come from?”. It has always seemed to me that answers to such questions would be very helpful for developing effective therapies for both the prevention and treatment of MS. In this column I will summarize my answers to these important, yet rarely addressed, questions.

Most researchers agree that MS was probably very rare before 1800 and, previous to that time, there are only a very few records of a person having the rather distinctive symptoms and disabilities that we now label as MS. By the early 1800s MS seems to have affected enough people in France and Britain that many more records are available. By the mid part of the 19th century MS was recognized as a distinct disease and, as the population of the first world grew, MS prevalence grew with it and today it is estimated there are perhaps as many as two million people with MS.

So why did MS start to become so common about 200 years ago such that it was seen as a distinct disease? The answer to this lies in understanding the environmental factors that drive MS onset and progression and when and why such factors started to affect large parts of the population.

It is widely accepted that MS is an autoimmune disease which means the disease process is driven by one’s own immune system. Autoimmune disease involves the activation of immune cells that are sensitized to one or more self-proteins as well as the failure of the regulatory side of the immune system to suppress such potentially harmful reactions. In MS, the immune system becomes sensitized to and attacks proteins in the myelin sheath that protects the axons of the central nervous system. Such attacks on the myelin are not well controlled by immune suppression such that substantial damage often occurs and clinical symptoms become apparent. Given this understanding of the MS disease process, the obvious questions become “what environmental factors cause the activation of the myelin-sensitive immune cells?” and “which factors ensure that such attacks are not well controlled through immune suppression?”.

Research has revealed that fragments from foreign proteins derived from infectious agents and foods can activate myelin-sensitive immune cells through cross-reactions. Notably, many new foreign proteins were introduced into the human environment by the agricultural revolution, 10,000 to 5000 years ago. Such new proteins came from numerous infectious agents that crossed over to humans from domesticated animals (eg Epstein Barr virus) and from completely new food types such as dairy, grains and legumes. These new proteins had a great potential to cause autoimmune reactions because of the lack of any evolutionary experience with them.

However the introduction of these new proteins by agriculture apparently did not cause widespread MS and other autoimmune diseases because most people still had adequate immune regulation and were able to suppress any potentially harmful autoimmune reactions caused by the new proteins. Most people had adequate immune regulation because of an adequate supply of vitamin D and omega 3 EFA, established immune regulators, and also the occurrence of many chronic infections in childhood related to the unhygienic conditions of those times. Such infections result in well-educated immune system capable of optimal immune suppression.

Notably, in the early 1800s there was a substantial reduction of vitamin D supply due to the industrial revolution and there was also a major reduction in common childhood infections due to the establishment of hygienic conditions. These reductions resulted in many people no longer having an adequate capacity to suppress autoimmune reactions. This reduced suppression capacity within the population, combined with the already common presence of foreign proteins that could initiate autoimmune reactions, resulted in some of the people who were genetically susceptible to MS actually contracting it. Hence MS started to affect a large enough number of people that it was seen as a distinctive disease during this time.

The situation has gotten even worse over the last 100 years. Vitamin D intake has continued to decline due to more and more people having urban office jobs rather than outdoor, rural ones. The specter of skin cancer and the development of sunscreens have added to widespread vitamin D deficiency. Hygienic conditions have been improved such that most first world people live in an ultra-hygienic world. Children have only rare infections and consequently also have an undereducated immune system that has a greatly reduced capability for immune suppression. Finally, even omega 3 EFA intake has been greatly reduced due to a change from grass-fed domesticated animals to grain-fed ones.

In summary, the loss of immune regulation capacity over the past 200 years, in combination with the already present, cross-reactive antigens introduced earlier by agriculture, unleashed the MS monster in first world populations. This analysis leads to the insight that MS rates can be greatly reduced if first world societies either remove the problematic foreign proteins or substantially increase the immune suppression capacity of the population. It would be next to impossible to remove most of the foreign proteins so the obvious solution is to boost immune suppression capacity. Ensuring that all children receive adequate vitamin D and omega 3 EFA can readily do this and such a strategy would likely reduce MS to a very rare disease. For those with MS, the obvious strategies are to both remove the potentially cross-reactive food proteins and to boost immune regulation capacity through supplements of vitamin D and omega 3 EFA.

back to top

MS and First Do No Harm

First of all I would like to thank Judy Graham for inviting me to write a column entitled “MS and” in New Pathways, which is undoubtedly the best publication available for persons with MS. I am planning to write mainly about various issues including the science behind different types of therapies and specific scientific phenomenon involved in MS. I am also going to take this opportunity to air a few of my pet peeves that I lump together as the crippling politics of MS. I decided to start with one of these topics and this column is on the obvious but never-mentioned problem of a lack of consistency between the well-known dictum “First Do No Harm” and the current actions of MS researchers.

Most MS researchers are doctors (MDs) rather than formally trained scientists (PhDs). Doctors claim to follow the laudatory and common sense goal of “First Do No Harm”. For the MS researchers this oath translates to “First Do Research that Leads to Therapies that Do No Harm” and our main question is whether or not MS researchers come remotely close to following this maxim.

The widely accepted autoimmune model of MS disease process guides the MS research effort. In brief, this model appeals to foreign proteins to activate myelin-sensitive T cells that then cross the blood-brain barrier and initiate an immune attack on myelin proteins in the central nervous system. A failure of the regulatory portion of the immune system to contain the autoimmune attack is also an important facet of the model The consequent immune destruction of myelin and underlying axons is the cause of the various symptoms that characterize MS.

There is a large body of scientific evidence that supports this model and it is reasonable that it is used as the key foundation of the MS research effort. Given this model and the desire to First Do No Harm one might expect the researchers to be concentrating on elements of the interpreted disease process that can lead to therapies that cause no harmful side effects rather than on elements that would lead to therapies involving substances that have substantial toxicity.

The autoimmune model for MS directly leads to the deduction that both infectious agents and foods can contribute proteins that can activate the myelin-sensitive T cells and abundant research supports this. It also leads to the interpretation that nutritional deficiencies that result in reduced immune regulation may well be involved in MS. Given that if certain foods could be identified as being activators of autoimmune reactions in MS, then the avoidance of such foods would be a potential “no-harm” therapy. Unfortunately extremely little research is being done on the potential involvement of various food proteins in MS and the potential for diet modification to be an effective therapy. Another obvious area of research for the development of no-harm therapies would be examining whether or not deficiencies in vitamin D and omega 3 essential fatty acids, both established immune regulators, are involved in MS. Once again very little research is being done on these nutrients in regards to MS.

Almost all the MS research effort goes towards the identification of specific molecular interactions that are involved in the MS disease process. The goal here is to identify a drug therapy that counters one or more of these molecular interactions. An inherent problem with such an approach is that the derailing of a putative harmful molecular interaction, which in almost all cases has beneficial purposes as well, results in harmful side effects. The recent Vioxx debacle is a fine example of this problem. Thus such drug development research is anything but an attempt to “First Do No Harm”.

It is clear that the MS researchers have not made the investigation of nutritional factors that are plausibly involved in MS as their priority as would be expected if they wanted to First Do No Harm. Their overwhelming priority is the development of semi-toxic drugs to treat MS. This complete lack of balance in research effort cannot be justified on scientific grounds because both research paths have the potential to yield an effective therapy. The main reasons for the priority of drug development research are generous grants from drug companies, possible large financial rewards from patents and potential fame and prestige in the research community and beyond. Nutritional research does not offer these researcher-centred benefits to the researchers.

It is perfectly understandable that the MS researchers have chosen potential fame and fortune through research that leads to harmful therapies and have avoided doing research that would lead to “no harm” therapies. Such actions are readily understood when viewed in an evolutionary perspective in which the researchers are trying to improve their fitness and chance of survival through the attainment of wealth and higher status.

The only nagging problem is that the MS research community is not acting in the best interests of those with MS by not researching therapies that “Do No Harm”. There are a number of obvious “no-harm” therapies such as vitamin D supplementation that are begging for laboratory and clinical research. Such “no harm” therapies won’t make much money for anyone but they might well make a huge difference in the lives of persons with MS. I wonder what it will take to persuade the MS research community to “do the right thing” and pay more than lip service to their favourite motto of First Do No Harm.

back to top

Nutrition Factors and Multiple Sclerosis

Part one: Identifying the Prime Suspects

Dietary factors are an important part of many chronic diseases, including heart disease, hypertension, osteoporosis, diabetes, and even cancer. With this in mind, one may ask if dietary factors are also part of the MS disease process. Currently, no clear-cut scientific data demonstrate, beyond a reasonable doubt, that various components of diet do or do not play a significant role in MS. Therefore, no definitive statements may be made regarding the diet’s effect on MS, and whether or not dietary changes can help slow MS progression.

This is the first of a series of articles that will objectively look at the scientific data that implicate a variety of nutritional factors in the MS disease process. On the basis of this information, suggestions will be provided for dietary revision that could have the potential to positively affect the MS disease process and slow the addition of disabilities.

By providing such information, individuals with MS are given a dietary strategy that may be helpful; however, anyone considering any changes to his or her diet should do so only under the guidance of his or her physician. Please note that while much data is available, no rigorous clinical trials have been conducted to definitively determine if dietary changes can affect the onset and progression of MS. Plans are now underway for a clinical trial which will look at the effects of diet on MS. It will involve MRI scans, neurological exams, and immune markers carried out over a two-year period.

Many scientific articles have been published on various aspects of nutrition and MS, as well as closely related diseases. These allow a reasonable assessment of the possibility for various nutritional factors to be involved in MS. Currently, nutritional factors that have been determined as “prime suspects” in MS include: various common protein-bearing foods such as dairy products, gluten grains (wheat, rye, barley), and legumes; as well as chronic deficiencies in vitamin D, fish oil, and anti-oxidant vitamins, minerals, and phytochemicals.

These “prime suspects” were identified by utilizing the scientific database in two different ways. The first way is best described as logical deductions from the current understanding of the MS disease process, that is, the way Sherlock Holmes would solve a crime. A great deal of research over the past 30 years has left little doubt that MS is an autoimmune disease in which a person’s own immune cells attack and damage tissue in their central nervous system (CNS). Thus a key question is, “What nutritional factors have the potential to help the immune cells to attack the central nervous system?”

Potential candidates are both nutritional factors that can stimulate immune cells to attack the CNS, and those factors that can decrease the body’s ability to suppress such an attack. All of the above named nutritional factors seemed to ”fit the bill” at this stage of analysis. Various proteins in foods clearly had the potential to stimulate immune cells, while deficiencies in vitamin D, fish oil, and antioxidants can hinder the suppression of harmful immune reactions.

This next task involved a thorough review of the MS scientific literature to find out what reliable data existed to support or deny the involvement of the initially identified, nutritional “prime suspects.” Such scientific information included data on animal experiments as well as studies of the molecular composition of various food components (vitamin D and dairy proteins for example) and their effect on the immune system. Also of great importance were the studies of the nutritional habits and status of various populations and the rates of MS in those populations.

Finally, important data came from a number of small clinical trials that used a nutritional factor as the tested therapy for MS along with closely related autoimmune diseases such as rheumatoid arthritis. When all of these data are considered together, a reasonable assessment can be made as to whether or not a reasonable chance exists that a given nutritional factor plays a role in MS. If the available science points the finger at a given nutritional factor, for example a deficiency in a certain vitamin, then individuals with MS may potentially benefit from a strategy that ensures they are getting an adequate intake of that vitamin.

The continuing series on nutritional factors and MS will look at each of the identified ”prime suspects” – common protein-bearing foods as well as chronic deficiencies in vitamin D, fish oil, and anti-oxidants – and present the scientific data which implicate each one in the MS disease process. Strategies on how one might change his or her dietary habits (under the guidance of a physician) to offset the effects of each of the “prime suspects” will be given. In the next issue of The Motivator, evidence linking vitamin D deficiency to MS onset and progression will be reviewed, along with the controversial claim that MS could be a vitamin D deficiency disease.

Editor’s note: Any vitamin which is not water-soluble, including vitamin D, may be stored in the body if too much is taken, and this may result in toxicity. Readers are cautioned to contact their physician before making any changes to their diet or supplement regimens.

back to top

Nutrition Factors and Multiple Sclerosis

Part II Vitamin D

In the Health and Wellness column in the last issue of The Motivator, the concept that various nutritional factors play roles in the onset and progression of MS was introduced. In that column the “prime suspects” were identified on the basis of the available scientific evidence. A deficiency in vitamin D, the sunshine vitamin, was one of the nutritional factors that appear to figure prominently in the MS disease process.

Vitamin D first reached the public’s attention in the 1920s when it was isolated and named. At that time it was shown that a deficiency in vitamin D was responsible for rickets, a serious bone disease that affected many children in North America and Europe. The main source of vitamin D for most people comes from the sun. Notably vitamin D is found only in very few foods with fatty fish such as salmon and mackerel being the best sources. When skin is exposed to ultraviolet B rays of the sun, cholesterol in the skin is converted into vitamin D. The vitamin D is then transported to the liver where it changes form and is released into blood circulation. Many cells in the body from the kidneys to the brain to various immune cell types, convert the circulating vitamin D into an active hormone that is required for proper cell functioning.

The action of this vitamin D hormone is usually associated with its ability to facilitate the absorption of calcium from the intestines. Calcium is a mineral that is essential for many critical physiological functions and thus vitamin D’s role in this regard is of the utmost importance. When vitamin D levels are too low, various biochemical reactions occur to ensure calcium levels are maintained and one result of these actions is the loss of calcium from the bone. Thus a long-term deficiency in vitamin D may result in osteoporosis in later adulthood.

Cells of the immune system also require vitamin D for proper functioning. This is why vitamin D deficiency may well be a factor in MS, a disease of a malfunctioning immune system. A deficiency in vitamin D was first hypothesized to be a significant factor in MS 30 years ago when it was noted that variations in rates of MS closely followed changes in vitamin D supply. For example, in Australia, where there are very large variations in the rate of MS, the MS rate correlates almost perfectly with the supply of ultraviolet light from the sun, the main source of vitamin D. A similar relationship has also been documented in North America and decreasing sunshine and vitamin D supply provides a ready explanation for why MS is four times as common in Washington state compared with southern California.

Notably other very diverse scientific data also support the concept that a deficiency in vitamin D plays a major role in MS. Animal experiments have demonstrated that injections of vitamin D hormone or just simple exposure to ultraviolet light will prevent or halt the animal form of MS in mice. Immunological studies reveal how vitamin D plays an important role in affecting the MS disease process that is dominated by the attack of immune cells on myelin, the fatty substance that wraps around nerve axons in the central nervous system. It has been shown that vitamin D hormone can significantly slow down such an immune attack by preventing the problematic immune cells from multiplying.

Other important scientific evidence which demonstrates that vitamin D is involved in MS includes a study which showed that nurses who took a vitamin D supplement had a 40% lower risk of MS, a study which showed that people who work in jobs where they are exposed to lots of sunshine had low rates of MS and a study which showed that people who were exposed to lots of sunshine as children had an 85% lower chance of contracting MS.

Most studies provide good evidence that adequate vitamin D can prevent the onset of MS in many cases. An obvious question becomes can adequate vitamin D affect MS disease activity in those who are already diagnosed with the disease. In the 1980s a small clinical trial using 5000 IU of vitamin D a day demonstrated a marked reduction in attack rate over the 2 years of the study. However the study was quite small so the results need to be confirmed by a larger better-controlled study. Recently, in a small study that used fish oil, a good dietary source of vitamin D, as the therapeutic agent, 85% of the participants went attack free over the two-year study period. Finally it was shown that MS disease activity, as revealed by lesion activity on MRI scans, increased and decreased in concert with seasonal changes in vitamin D levels of the participants.

People who live in latitudes greater than 35 degrees (most of the USA and Europe) do not make much vitamin D for up to 6 months of the year because of the low angle of the sun in the winter months and a consequent substantial lessening of UVB rays. That is likely the main reason why MS is so common in these higher latitudes. It has been estimated that humans use up to 4000 International Units (IU) of vitamin D a day and that many people in the higher latitudes average only 500-1000 IU/d from all sources over the year. This relatively low intake results in a fluctuating blood level of circulating vitamin D of 20-30 ng/ml. This is about half of the estimated optimal level of 40-60 ng/ml which is found in persons in lower latitudes where MS is rare. This deficiency in circulating vitamin D results in many cell types, including immune cells, not being able to manufacture adequate vitamin D hormone for proper functioning.

Given all of the above it would seem that it would be wise for persons with MS and their close relatives who have a higher susceptibly to MS to ensure they have an optimal amount of circulating vitamin D so that all their cells, especially their immune cells, have access to all the vitamin D which is required. Vitamin D supplements provide one way on accomplishing this. Increased sun exposure would be of benefit for increased vitamin D but this may also raise the risk of skin cancer. Because of differences in genetics, lifestyle, geographic location and sun exposure, the amount of supplement required will differ from person to person depending on their individual circumstances. Each person with the help of their physician can determine what level of supplementation is needed to ensure their circulating blood level of vitamin D stays above 40 and below 60 ng/ml. For many people an adequate supplement level seems to be about 4000 IU/d from October to March and 2000 IU/d from April through September. However it is emphasized that yearly checks of one’s circulating vitamin D level and a discussion with their physician are essential for making sure one’s level is not too low or too high.

In summary, a very diverse scientific database indicates that lower than optimal levels of circulating vitamin D are associated with MS. Persons with MS and their close relatives may want to consider using an adequate vitamin D supplement, especially in winter, to ensure they do not become deficient in this very important nutrient.

back to top

Death and Dividends: The Tysabri Debacle

For the last three to four years neurologists have been talking about the coming of a much more effective drug for MS. That drug was first called Antegren and then Tysabri. The story of Tysabri illustrates some risky and unsavory aspects of the search for an effective drug for MS.

Tysabri is a humanized, monoclonal antibody that is produced by transgenic goats in their milk. A monoclonal antibody is a designer drug that targets one specific protein in the body and basically knocks it out of action. MS research has led to the concept that MS is driven by activated T cells that are sensitized to myelin. Such autoreactive T cells are activated in the blood mainly through an immune encounter with a foreign protein from an infectious agent or food. The activated, myelin-aggressive T cells then migrate to the brain, pass through the blood-brain barrier and lead an attack on the myelin. It was reasoned if a drug could stop or greatly hinder the passage of these autoaggressive T cells across the blood-brain barrier, then the MS disease process could be substantially short-circuited. Activated T cells cross the blood-brain barrier by sticking on the blood vessel wall and then pushing through it. A monoclonal antibody, which was to become Tysabri, was developed to knock out the protein on the T cells (VLA-4) that allows them to stick on the blood vessel wall.

Preliminary studies indicated that Tysabri was seemingly safe over the short term with a few bad allergic reactions being the only notable adverse effect. By 2001, Elan and Biogen, the drug companies which were producing Tysabri, predicted billions of dollars in future revenue and their stocks started to soar. The Phase III trial began in late 2002 and, after only one year, the companies applied to the Food and Drug Administration (FDA) in the USA to approve the drug despite the fact that there wasn’t any evidence that it slowed disease progression. At the same time the drug was also tested for Crohn’s Disease, a gastrointestinal autoimmune disease, but was found to have no significant effect. One person on Tysabri in the Crohn’s trial died of apparent brain cancer.

In November of 2004 the FDA approved Tysabri for use on the basis of the first year result of fewer attacks and MRI-detected lesions and soon afterwards neurologists were infusing their patients with this new, very expensive drug. The company stocks climbed to new heights.

The last two weeks of February, 2005 were very eventful. On February 14 Biogen director, Robert Pangia, sold 15,570 shares for a profit of $954,844. On Feb 15, Biogen’s executive chairman, William Rastetter, sold more than 120,000 shares, yielding a $7.45-million profit. On February 18 Thomas Bucknum, a Biogen executive vice president and the company's general counsel, sold 89,700 shares for a profit of $1.9 million. Later that same day Biogen informed the FDA that one Tysabri patient had died of a very rare brain disease known as PML (progressive multifocal leukoencephalopathy)and that another patient also likely had the disease.

PML occurs when the JC virus, which most people carry, rises from a dormant state due to a weakened immune system and destroys the myelin in the brain at a very rapid rate. PML is a very ugly disease which usually ends in death over a few months. Given that Tysabri prevents T cells from entering the brain and thus reduces immunological control of the JC virus, it is extremely likely that it is the main cause of the PML.

On February 27, Elan and Biogen issued a glowing press release describing the results of the two-year Tysabri clinical trials. It sounded like the promised drug had arrived. On February 28 the FDA issued a terse statement stating that two Tysabri patients had PML and that the drug was being voluntarily withdrawn from use by Elan and Biogen. Both stocks fell like rocks with Elan losing 60% of its value and Biogen 40%. When questioned about the executives who had possibly made illegal stock trades, Biogen stated "All these trades preceded that quick and decisive action, which was guided exclusively by concern for patient safety and our commitment to the MS community". The Securities Exchange Commission will likely investigate whether or not insider-trading laws were violated.

Throughout most of March it was widely agreed that Tysabri would likely make a comeback as early as the fall. Then at the end of March came the news that the patient in the Crohn’s/Tysabri study who had supposedly died of cancer had actually died of PML. As I write this they are still debating whether or not Tysabri will be brought back despite its potentially fatal side effects.

There are a number of incidents connected with the Tysabri saga that need clarification. It is surprising the Biogen doctors misdiagnosed PML as brain cancer in 2003 especially when PML is a possibility with any drug that has a major effect on the immune system of the brain. Also it is unclear why it took at least a month after the PML cases were identified in the Tysabri and MS trials for the drug’s withdrawal to be announced. This delay put many people at great risk. Furthermore, is it just coincidence that the Biogen executives unloaded their stock during this questionable delay? It is also surprising that Elan and Biogen put out a press release saying how fantastic Tysabri is, knowing full well that the next day the FDA was going announce the suspension of the drug because of ties to a deadly brain disease. And why did the FDA approve Tysabri after only one year of the Phase III trial given the potential of long-term side effects of such a powerful drug as well as the less than stellar results. These are all troubling questions without answers.

Persons with MS should realize that participating in a clinical trial is somewhat like playing Russian Roulette and that a drug company’s desire for maximum profits may compromise their efforts to ensure maximum protection against harm. Drugs that short-circuit the immune system have bad side effects and death is always a possibility. Copaxone and the beta-interferon drugs are cakewalks compared to what is coming down the pipe. The drug companies know that any new “blockbuster” drug, such as Tysabri, has to be significantly more effective than the current drugs and that means they will likely be much more damaging to the immune system.

I always find it incredible that many people recently diagnosed with MS will choose a potentially deadly drug over nutritional strategies that are completely safe and likely more effective. Luckily there are still some people with common sense who do not allow themselves to be sacrificed for profit.

back to top