Multiple Sclerosis 6- Oxidative Stress 1

In clinical circles, the term "oxidative stress" is used frequently.  You may have heard people talk about oxidative stress-inducing "free radicals" and how their influence is counteracted by "antioxidants."  Simply put, oxidative stress refers to a chemical instability that disrupts the function of cell membranes, enzymes and overall cellular function.  Oxidative processes are a normal part of human physiology but our built-in checks and balances system allows "antioxidants" to blunt any potential harm.  Many of these antioxidants are derived from our diet while other are synthesized by our body.

One study found that higher levels of oxidative stress were associated with further decline in function among MS patients.  Interestingly, this decline happened even though the appearance of lesions on MRI did not change.The authors conclude, "This process [oxidative stress] could be at least partially responsible for ongoing functional decline in SPMS (secondary progressive multiple sclerosis)." Mult Scler 2010 Oct 4 (epub)

In a sense, it is probably best to regard oxidative stress as a byproduct of the disease process rather than as a direct cause.  Let's think of it this way;  if a team of bandits came through your neighborhood setting houses on fire, there is going to be a massive amount of destruction.  As the fires blaze away, the bandits enjoy the cover of smoke and chaos and set even more houses on fire.  That team of bandits can be compared to any disease process; in our case, MS.

Oxidative stress is likened to the flames coming out of the homes.  While the bandits were the cause of the problem, the flames themselves lead to destruction, fear and bodily harm as well.  It is in our interest to put out those flames. 

A paper out of the University of Wisconsin-Madison compares the threat of the bandits versus the threat of the fires.  The authors describe the attack on myelin by immune cells and go on to state, "Secondary to these events, however equally destructive, is the generation of inflammatory-mediated reactive oxygen and nitrogen species generated by persistently activated microglia and astrocytes."  They suggest that by increasing our production of antioxidants (and detoxification agents),  we may "attenuate pathogenesis of autoimmune diseases such as MS..."   Toxicol Sci 2010 Apr;114(2):237-46.

Regarding the primary treatment of MS with interferon and other pharmaceuticals, one author writes,

"disease progression, although typically delayed with these agents, remains inevitable in most patients and constitutes a significant limitation of the currently available treatments....a better understanding of pathophysiologic factors in MS--such as the role of neurotrophic growth factors and oxidative stress--are changing the ways that efficacy is measured and how new agents are developed."   Am J Managed Care 2010 Sep; 16(8 Suppl):S211-8.

Clearly, oxidative stress is a force to be reckoned with.  In the next post, I'll discuss strategies to counter oxidative stress.

Multiple Sclerosis 5- Omega 3 Fatty Acids

The point of this series on MS is not to provide alternatives to conventional management.  Rather, we need to identify all the options that are complementary.  This article states that the complementary therapies, "most frequently used include diet, omega-3 fatty acids and antioxidants." Expert Rev Clin Immunol 2010 May;6(3):381-95.

You may find it interesting that modalities that are often attributed to simply being part of a healthy lifestyle are now considered to be a therapy.  We have come to the point where a healthy diet is now considered "therapy" rather than being a mainstream, commonplace habit.  

Many people, even those without disease, use omega 3 fatty acids.  Their heart and brain-protective effects have been well documented.   They are also well accepted as being a potent anti-inflammatory agent.  As inflammation is so common in a variety of diseases, omega 3s may be helpful in conditions ranging from fatty liver disease, depression, osteoporosis, and of course.... multiple sclerosis.

One study examined the therapeutic use of omega 3 fatty acids on several immune markers.  The researchers found that one particular indicator of immune activity, matrix metalloproteinase-9, was reduced after 3 months of aggressive supplementation (9.6 grams/day.  Many experts recommend 1 g/day for general health purposes).  The authors conclude that  "omega-3 FA may have a potential therapeutic role in RRMS (relapsing-remitting MS) patients." Prostaglandins Leukt Essent Fatty Acids 2009 Feb-Mar;80(2-3):131-6. Epub 2009 Jan 25.

Several animal studies also show promise in the use of omega 3s in MS management.  DHA, a component of fish oil, was shown to calm the immune response in experimental autoimmune encephalomyelitis, the animal model of MS.  Given the promise of modulating the immune response (and therefore the attack on myelin), researchers continue to actively investigate the possible use of MS.  Currently, the use of fish oil is not a standard of care in MS management. Results of many other scientific studies have been mixed.

But while researchers figure this out, what will you do? One option is to wait another 10 years for more conclusive data to emerge.  Another option is to recognize that sick or healthy, omega 3 fatty acids are necessary for ideal physiological outcomes.  Omega 3s are not a magic pill that will cure MS.  Perhaps taken alone, they may have minimal effect.  But what if omega 3s calmed inflammation, vitamin D helped modulate the immune response & probiotics restored normal gut activity?  Could there be a synergistic effect that will take decades for science to quantify? (I mention these 3 because these were mentioned in previous posts. There are, of course, other options).

I will admit that figuring out the appropriate dosage of omega 3s can be tricky.  As mentioned, many people take 1 g/day while the therapeutic dose used in some trials is over 9 grams.  But working with your physician, you should be able to monitor levels through simple blood tests that serve as a guideline. 

Multiple Sclerosis 4- Vitamin D

"It is believed that the active form of vitamin D has immunomodulatory effects on cells of the immune system, particularly T lymphocytes, as well as on the production and action of several cytokines" Rev Bras Reumatol 2010 Feb;50(1):67-80

Vitamin D has come a long way in the past decade.  We used to appreciate vitamin D for its role in promoting calcium absorption at the gut.  This is still the case, but we now see that vitamin D has so many more exciting roles in the body.  One of the most intriguing is its role in modulating the immune system.  

Let's remember that nearly 3/4 of Americans have low levels of vitamin D.  Experts universally agree that raising vitamin D levels is essential for optimal health.  There is some disagreement as to the dosage required, use of sunlight, tanning beds or fortified foods.  But we all agree that low vitamin D levels are not good and may manifest in a number of different ways.

"A growing body of evidence supports a role for vitamin D in MS aetiology."J Neurol 2010 Nov 2.

 "...it would appear likely that hypovitaminosis D is one of the risk factors for multiple sclerosis." Brain 2010 Jul;133(Pt 7):1869-88.

"Experimental animal models of MS reproduce the beneficial effects of vitamin D..." Nutr Rev 2008 Oct;66(10 Suppl 2):S135-8.  

The list goes on and on with general agreement that vitamin D deficiency is a very serious issue with respect to the cause and progression of multiple sclerosis.

Vitamin D levels can be easily assessed.  While 25 OH levels are typically the vitamin D form that are measured in blood, it may be worthwhile to also measure 1,25 dihydroxy vitamin D, the active form of vitamin D.  Closely monitor these levels as people may respond differently to the same dose.  If you have MS, it is in your best interest to maintain healthy levels of vitamin D.

Multiple Sclerosis 3- Gut

The gut appears to have particular significance in managing MS.  It is an emerging area of research so let's look at some recent findings.

In one study, alterations in the gut microbiota (in mice) significantly altered the susceptibility to autoimmune encephalitis.  (Autoimmune encephalitis is the experimental model for multiple sclerosis in mice.)   In this particular paper, mice who were put on antibiotics to wipe out the bacteria in their guts fared better than those that did not take antibiotics.  Based on what we know about gut microbiota, this may be somewhat surprising as we generally think of these bacteria as protective.

However, the authors conclude that "microbial populations that selectively persist in the gastrointestinal tracts of mice treated with antibiotics... could be inducing the antiinflammatory reactions reported in this study."  In other words, there are bacteria in the gut that seem to have a protective effect in this condition.

These findings were confirmed by researchers at Cal Tech.   These researchers state, " intestinal microbiota profoundly impacts the balance between pro- and antiinflammatory immune responses..."  They go on and "suggest that modulation of gut bacteria may provide therapeutic targets for extraintestinal inflammatory diseases such as MS."

 If these findings are accurate, then it would appear that healthy gut bacteria are necessary to protect the brain from inappropriate immune assault.  We do not know to what extent this protective effect exists.  We do not know what co-factors are necessary. We do not know to what extent healthy gut microbiota reduce the progression in those individuals already with the disease.  There is so much we have to learn.  But this much is clear; disrupted microbiota massively influence immune function.  The degree and extent of immune disruption is related to MS.

Let's try and make this meaningful to the current MS patient; it stands to reason that maintaining a healthy gut should have some priority.  This line of research opens up new questions that are pertinent to individuals with MS.  What destroys gut bacteria?  What foods?  Additives/preservatives/toxins? Lifestyle habits? How can I maintain a healthy balance? 

A healthy gut is essential for everyone; with or without MS. 

Multiple Sclerosis 2- Gluten

Gluten may have a role in multiple sclerosis... for some people.  In a study of 98 patients with confirmed MS, researchers "found a highly significant increase in titers of immunoglobulin G antibodies against gliadin and tissue transglutaminase in the multiple sclerosis patients."  

They concluded that while "the specific role of these antibodies in the pathogenesis of multiple sclerosis remains uncertain and requires additional research. A gluten free diet should be considered in specific cases of patients who present with gluten antibodies." Ann NY Acad Sci. 2009 Sep;1173:343-9.

Other studies have also suggested a link between MS and gluten although several studies have also refuted any association.  Clearly, we can't make a blanket call for everyone with MS to avoid gluten.  But it is reasonable cause for investigation.  If true, it makes case studies such as this one more understandable. In that paper, the authors suggest that gluten may have triggered, "inflammatory immune-mediated damage of the central nervous system" that presented as MS. Neurol Sci. 2008 Feb;29(1):29-31. Epub 2008 Apr 1.

Gluten is a protein found in wheat, barley & rye (most oats are contaminated with gluten).  At first glance, any association between a grain product and MS may seem absurd.  But when you realize that many individuals have an aberrant immune response against gluten (for reasons not entirely understood), then some similarity with MS becomes a bit more apparent.  In celiac disease, the immune system attacks gluten and often attacks components of our gut.  In MS, the immune system attacks the structures of the central nervous system.  Same army- inappropriate attack in both circumstances- different location.

In fact, there is even a relationship in the genetics behind these two seemingly separate diseases. 

Again, we should avoid making blanket statements about any complex chronic disease.  But it seems appropriate to rule out any involvement of gluten.   

Multiple Sclerosis 1- Complexity

There is no cure for multiple sclerosis.  It's a debilitating (to varying degrees) disorder that affects 300,000 people in the United States; most of them, women. In the coming weeks, I will be posting on multiple sclerosis and the utility of a functional medicine approach toward its management.   Conventional management of the disease has become more sophisticated in the past decade but emerging research may guide us toward more effective care in the future.  You can read about conventional care of MS through this Emedicine website.  Another great resource to keep abreast the current research can be found through the Lancet website. 

For many chronic diseases, functional medicine offers safer and often better options for management.  MS is a condition where a truly integrative approach between conventional and so-called "holistic" care may be ideal.  MS is an autoimmune disease that attacks myelin in the central nervous system.  It is often referred to as a 'demyelinating disorder.'  This means that the fatty sheaths that cover nerve cells are destroyed.  

Multiple sclerosis, while traditionally categorized as a neurological disorder, is actually a disease of immunity.  I realize this is hardly ground-breaking news, but once we really accept that fact that it is immunity gone haywire, it will open up options to approach this disease.

Is MS the result of a "pissed off" brain or a "pissed off" immune system.  Of course it is the brain but only as a consequence of the PO'd immune system.  This leads to the question; what PO'd the immune system?  Was there a provocative agent that made him turn on himself?  There is certainly a genetic component and some of the environmental factors have been identified. For example, researchers have long understood that latitude is significantly related to disease onset.

We'll look at MS through the lens of integrative physiology in the coming weeks.  By the end of this series, I want readers to be convinced that eating well and maintaining a healthy lifestyle are an absolutely essential part of management.  Many doctors and patients have the opinion that a healthy diet and lifestyle are important, but not of critical significance.  In other words, talk of a healthy diet gets a generic head nod and mumbled agreement while the tilt of the conversation moves toward "sexy" therapies like interferon or medications taken concurrently to reduce spasticity or pain.

Patients and doctors managing MS are a zealous lot; weeks of research and aggressive reading into the most suitable therapies.  My hope is that patients and doctors will invest equal time and energy into managing food intake and lifestyle habits.