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.

Low back pain 6- Central Sensitization

The mechanisms I described in the previous post  involve a process termed "central sensitization."  Let me explain.  The brain has a certain threshold at which it perceives pain.  This threshold is variable, not absolute.  In other words, there are moments when you have a lowered pain threshold and other moments when it is raised.  For example, if you are in the middle of an athletic event, your pain threshold is elevated because of a change in your neuroendocrine milieu.  A cut on your hand may not even be perceived until the game is over.  You don't actually feel "pain" even though the pain signals are being actively generated at the tissue.  While there are numerous places where this pain modulation occurs (spinal cord, brain stem, thalamus are a few...), it ultimately leads to a decrease in pain related activity in the brain.

"Central sensitization" is just the opposite.  When a pain loop has been running for some time, your brain gets really good at perceiving and running that loop. This can happen after an injury where a vicious cycle emerges to perpetuate the pain.

These authors describe one model where a painful stimulus may...

"...induce multiple inflammatory and neuropathic processes in the spinal cord dorsal horn, and trigger modification and plasticity of local neural circuits. As a result, ongoing noxious signals to the brain are amplified and prolonged, a phenomenon known as central sensitization."  Curr Pain Headache Rep. 2010 Jun;14(3):213-20.

Scientists are in agreement that this phenomenon occurs regularly.  The question that remains unanswered (although we can make educated guesses), is whether or not central sensitization is more likely to occur when there is pre-existing inflammation in the brain or the periphery.

Does an unhealthy physiology have a greater probability of allowing central sensitization to occur?  Does a person who eats well, has no inflammation, sleeps well, exercises regularly and manage his stress have a better environment that will resist the induction of these noxious pathways?

To be fair, we don't have a clear answer for this yet.  The science pretty much says, "maybe- but we can't preach that particular message with full confidence."  But when you consider the many health related "shades of gray" that brain can live in, when you consider our current understanding of pain physiology, when you appreciate the influence of food and nutrition on brain health and inflammation levels, it is not a giant leap of faith to believe that food is related to central sensitization.

If you know someone with chronic low back pain, I hope you are beginning to appreciate the absurdity of throwing multiple pain management modalities (ice, steroids, anti-inflammatory medications, exercises, physical therapy) at the individual without making fundamental changes to his diet.

Low back pain 5- Chemistry

Common mechanical causes of low back pain include disc herniations. Most clinicians acknowledge that if a tissue is damaged, there is a reasonable probability that it will produce pain.  In the 'old days', we used to believe that a disc herniation would pinch a nerve and lead to pain.  But as we realized that true nerve impingement (although it does occur) was less common than previously believed, the low back community began to look outward.

When there is tissue damage, lots of noxious chemicals are released. These chemicals are generally used to communicate with different components of your body that are responsible for healing and repair.  But it is becoming clear that these chemicals (broadly termed 'cytokines'), can be problematic if they persist.

This paper describes the production of inflammatory cytokines by damaged tissues. As they activate immune cells and the brain, the brain responds by promoting further release of these inflammatory triggers.  These authors describe the way that these signals cross the blood brain barrier and influence our perception of pain through a "cascade of altered neural activity."  This can promote the efficiency of the "pain pathways" to the brain and lead to persistent pain.

So far, so good.  But another question remains; is there anything else that leads to the production of these inflammatory cytokines?  In other words, can another event, apart from tissue damage at the low back, produce these nasty chemicals.  If so, then this would have the potential to make relatively minor tissue damage... a REALLY BIG DEAL.  The answer is a resounding yes.  Before we detail some of these components, picture this.

Have you ever caught a friend at just the wrong moment? Perhaps you made an innocent comment, "I like your other shoes more than the ones you're wearing."  And all of a sudden, your friend explodes!  It may have been a minor statement, but if she just got fired from her job, broke up with her boyfriend, had her credit cards stolen and her car is making funny noises, then your minor statement was the "straw that broke the camel's back" in an already traumatic day. 

If your brain is already compromised by a poor diet and lifestyle, then even a minor stimulus will lead to a major symptomatic eruption.  Remember, the brain not only maintains normal body mechanics, but also perceives pain.  Alteration in its function can heighten sensitivity and generate vicious cycles of pain.

Low back pain 4- Brain

We have further evidence that there are central neurological changes in individuals with chronic low back pain.  In this study, researchers found that in people with chronic low back pain, there was a decrease in gray matter in both the thalamus and prefrontal cortex.  The authors go on and state, 

"We hypothesize that atrophy of the brain circuitry involved in pain perception may dictate the properties of the pain state, such that as atrophy of elements of the circuitry progresses, the pain condition becomes more irreversible and less responsive to therapy."

In other words, the longer you have pain, the more that pain will establish itself as a regular part of your life by "rewiring" your brain.  At the very least, research like this suggests that in order to ameliorate low back pain, we must not only correct your peripheral structures (muscles, joints), but also address the brain.

Other experts agree with this idea.

"There is increasing evidence that chronic pain problems are characterised by alterations in brain structure and function. Chronic back pain is no exception. There is a growing sentiment, with accompanying theory, that these brain changes contribute to chronic back pain..." Man Ther. 2010 Jul 23. [Epub ahead of print]

Where does this leave us?  It suggests that everything we know about maintaining the health of your brain applies (to varying degrees) to chronic low back pain.  Brain research has exploded in the past 2 decades and we now recognize a variety of mechanisms to compromise the brain; inadequate nutrition, oxidative stress, stress hormones, lack of sleep, environmental triggers, gluten (to those who are sensitive), lack of exercise and so much more!  

There is truth to the thought that low back exercises will aid in brain function.  However, if those exercises are performed and the brain is then swamped with a Happy Meal (and the saturated fat, blood sugar surge, oxidative components, noxious chemicals, trans fats etc.) as you drive home from your physical therapy session, you are working against yourself.   Your are trying to re-wire the brain with the exercises, and then proceeding to assault it with your diet.  Food and low back pain are related.

In the next post, we will address other metabolic perspectives on low back pain. 

Low back pain 3- Respiraton

The diaphragm plays an important role in maintaining core stability.  It serves as the "top" of the core and its activation is timed to the activation of the abdominal muscles.  We know that in many cases, individuals with low back pain have altered respiratory patterns.  Spine. 2010 May 1;35(10):1088-94. 

In fact, some people that reach a plateau in their 'typical' treatment of low back pain respond quite well to breathing exercises.  Also, other researchers have discovered that in some individuals, problems with the diaphragm (and the subsequent low back pain), are coupled to failure to activate muscles of the pelvic floor.

We now have a picture of a person with low back pain and poor respiratory patterns (primarily chest breathing rather than using abdominal breathing techniques).  This person also fails to activate muscles of the pelvic floor.  We don't think of these muscles often unless we have a problem with urination (these muscles are trained during 'potty training') but they are also activated unconsciously as we stabilize the low back. 

The overriding question is; why do these muscles fail?  To answer that, we have to know what turns them on.  These muscles are activated by unconscious pathways from the brain and brainstem.  In other words, the nervous system turns on these muscles.  "Big deal" you could ask.  All muscles are activated by the nervous system.  The point that I want to make here is that it is generally recognized by the rehabilitation community that muscles do not fail.  Instead, the neural components that activate them will fail.  In other words, muscles don't tend to get truly "weak".  They tend to get "not activated" secondary to inhibition of those parts of the nervous system. 

As we dig deeper, we learn that the lower brainstem makes you breathe.  The lower brainstem is commanded by higher parts of the brain including the vestibular system. 

In other words a poor brain causes poor breathing which causes low back pain.  This is the missing "neuro" part that I wrote about in the previous post.  To be clear, I am not talking about a brain with true degeneration as in Parkinson disease.  I am talking about a brain that works at less efficiency or has a compromised level of integrity.

Low back pain 2

When you view low back pain, you can think of it from 2 perspectives.

1.  Biomechanical causes

2.  Metabolic causes

Most research has focused on the biomechanical causes of low back pain.  Truthfully, you could spend your entire life studying clinical biomechanics as it is a complex topic.  For example, in the 1980's, we thought you just needed to get some bed rest.  In the 1990's we realized that abdominal muscles were important in the stability of the back.  In the late 90's, gluteal muscles and legs were understood as important.  In the 2000's, there was an explosion of research on muscles with fancy names like; multifidus & transverse abdominis. And only fairly recently did many practitioners start appreciating the respiratory diaphragm and muscles of the pelvic floor.

As there are many practitioners who are skilled in this approach, I won't regurgitate this body of knowledge in this blog.  For more information, check out this blog by biomechanics expert, Will Stewart.  Will does a great job highlighting the importance of assessing all components of the kinetic chain from a variety of "real life" positions.  He also emphasizes a "real life" approach to rehab and exercise.  Great stuff and hours of mind-boggling reading.

I will mention that as we've learned more about the biomechanics of the spine, we've really come to appreciate the role of the nervous system.  While the term "musculoskeletal" has been around for decades, the term "neuromusculoskeletal" has been in use for the past 10-15 years as we've come to appreciate the role of the brain.

However, for most of those past 10-15 years, the "neuro" part has not been well described.  In the next post, I'll start there with the overall goal of bringing us into the metabolic arena.  I want to show you that to have a good biomechanical system, you must have a good "neuro"  system.  And to have a good "neuro" system, you must have a good endocrine and immune system.  And to have a good endocrine and immune system, you must eat well, manage your stress, sleep well and exercise... all the things that make you healthy.

Low back pain 1

Most of the entries I post in this blog have to do with metabolic issues (diabetes, obesity, inflammation etc.).  One of the underlying themes you may have gleaned by now is the integration of body systems.  Just when we think some component of our body works in isolation, science will demonstrate an intimate connection with other components of our physiology.  For example, in the series on heart disease, we saw how things like the gut, hormones, nutritional intake, and immune system influence the health of the heart.  For the next series, I want to tackle something just as prevalent; low back pain.

When you think of low back exercises, you may think of abdominal work.  If you find a more thoughtful therapist, he may recommend exercising the gluteal muscles (variety of squats or lunges) and stretching hamstrings.  An even more highly skilled therapist will integrate respiratory exercises and activation of muscles of the pelvic floor. Perhaps your therapist also examines the broader "kinetic chain" and examines your foot, ankle, knees and hips.  We often mistake this as a very sophisticated approach toward low back pain. I will admit that this is light years ahead of where low back rehab was just a decade ago, but we still have a long way to go.  

This paper changed my life forever.  In summary; 83% of patients who had chronic low back pain were found to have low levels of vitamin D.  They were treated with vitamin D and 95% of those treated had significant improvement in their symptoms!  The authors concluded, 

"Vitamin D deficiency is a major contributor to chronic low back pain in areas where vitamin D deficiency is endemic. Screening for vitamin D deficiency and treatment with supplements should be mandatory in this setting."

This paper was published in 2003 when I was in the middle of my residency.  In those years, I spent the vast majority of my clinical time performing physical rehabilitation on patients with musculoskeletal pain.  It irked me that the hours of physical exercise that my patients were performing may have been undermined by low vitamin D.  As more research uncovered the roles of vitamin D, it became clear that even something low back pain, more than likely, involved a intimate integration of physiological systems.

We'll take a closer look in the coming weeks.

The Future of America...unless things change

Another bleak report was published by the Centers for Disease Control recently indicating that the state of health in the U.S. in 2050 will be very, very sad.  They emphasize that unless things change, there will be an increasing number of diabetics.   We are reminded in this report that the health care costs associated with diabetes is $174 billion per year!

Experts predict that up to 1 in 3 American adults could have diabetes.   I've used the following example before but it's worth repeating; if I told you that 1 in 3 Americans would catch a virus that would significantly reduce their quality of life, consume massive amounts of health care dollars, cause kidney failure, blindness, nerve issues, sexual dysfunction, increase risk of many cancers, promote infertility and heart attacks.... we would be up in arms!  There would be a massive public outcry to develop a vaccine against this virus that could assault and destroy the lives of so many Americans.  

The real threat here is much more insidious.  I admit- eating lots of vegetables and exercising regularly is not quite as sexy as the idea of a brilliant team of scientists developing a new vaccine (cue the suspenseful music) against a ticking clock... to conquer this threat.  You probably won't see Hollywood make movies on how a healthy lifestyle can destroy this epidemic. 

Folks- you can change this.  I know it sounds a bit idealistic, but one bite at a time, one person- one family- one community at a time, we can prove these CDC scientists wrong.

The Role of Fathers

I've dedicated a reasonable portion of this blog to talking about the importance of Mom's health when she is pregnant.  Mom has the ability to make life-long impressions on the child's health depending on her health during pregnancy.   Mom's health can directly influence her child's susceptibility to diabetes, obesity & heart disease even as an adult.    But recent developments suggest that even dads have the potential for life-long influence over his child's health.

A paper published in Nature is titled, "Chronic high fat diet in fathers programs beta cell dysfunction in female rat offspring."  Researchers fed a group of male rats a high fat diet and made them obese.  These male rats impregnated normal weight, healthy female rats.  The female offspring had early signs of diabetes by the time they reached puberty.  And their beta cells (insulin secreting cells of the pancreas) actually had a distinctive gene expression compared to their healthy counterparts.

The researchers believe that the sperm of male rats changes with obesity. They believe there are epigenetic markings around the DNA of the sperm that influence the development of that child.  It should come as no great surprise when you understand the general principles of cell biology and epigenetics.  This will be welcome news to women trying to get healthy for the sake of their future children.  Now- dads have every reason to be on board with a healthy lifestyle!

Pregnancy- Essential Fats

Many people have heard of omega 3 fatty acids.  We see these advertised on infant formula, supermarket eggs and more.  Food manufacturers have begun fortifying many foods with this essential fat as it plays crucial roles in heart health, brain health, and in reducing inflammation.  You can easily find a bottle of fish oil (or an actual fish) in any supermarket.  Omega 3's are among the best researched nutritional supplement available and in our generally fish-deprived culture, a good supplement for most of us to take.

Omega 3s are especially important for the pregnant woman.  Supplementing with omega 3 fatty acids is a great idea, but women of child-bearing years should pay attention long before they get pregnant.  Experts believe that women consuming a traditional Western diet do not consume sufficient amounts of omega 3s to nourish the developing child. 

In late pregnancy, many women consuming contemporary Western diets may not be able to meet the fetal demand for n-3 long chain polyunsaturated fatty acids (LCPUFAs) from the diet alone.  Annu Rev Nutr 2010 Aug 21; 30: 237-55

In fact, much of the omega 3 available to the growing baby comes from Mom's fat tissue.  As Mom consumes omega 3 fatty acids, some are immediately utilized and other are stored in her fat tissue.   This becomes available to the growing baby throughout pregnancy and especially in the latter months.  The baby then utilizes some and stores some in his fat.  He will use these fats during the first few months of life. 

Omega 3 supplements should be a part of every woman's prenatal care.  Just as you would take a good prenatal vitamin with sufficient folate, omega 3s should also be included.

Metabolic Syndrome- Fetal Origins

There's no doubt that many of our lifestyle habits and dietary patterns powerfully influence our health; often, adversely.  Metabolic syndrome is a combination of many "famous" risk factors.  This includes hypertension, insulin resistance, dyslipidemia, promthrombotic state, abdominal obesity and a few others.  The American Heart Association has a great web page explaining metabolic syndrome.

Most health professionals acknowledge that metabolic syndrome is a consequence of poor lifestyle decisions and can be prevented by following common sense health principles.  But like many diseases, scientists are studying the origins and pathogenesis of metabolic syndrome.  As it turns out, the 'seeds' of metabolic syndrome may actually be sown during embryonic development. 

This paper states that "nutritional, hormonal, and metabolic environment afforded by the mother may permanently program differentiating target tissues of the offspring toward the development of metabolic syndrome/PCOS phenotype in adult life."

Stated differently, this simply means that a pregnant woman's health habits, including her diet, have the potential to radically affect her baby's health even as an adult!  This is something I've written about before.  It shows that the 9 months of intrauterine development may be the most important months of a human being's life.  If you didn't get a chance to read it yet, check out this piece from TIME magazine a few weeks ago.  It does a great job in discussing the most important months of your life.

Over 50 million Americans are affected by metabolic syndrome.  Wouldn't it be great if we could cut that number in half in a single generation?  Pregnant women, please take care of yourself. 

Pregnancy and Nutrition

Pregnancy is a time when women should pay extra attention to quality nutrition.  But an article in the Journal of the American Dietetic Association suggests that this may not be as easy as it sounds.  The article specifically highlights choline, a member of the B vitamin family.

Choline, like so many other nutrients, has many roles in the body.  One of the most famous roles is acting as a substrate to make acetylcholine, an important neurotransmitter.  It is also vital for cell signaling and maintaining the integrity of the cell membrane.  Choline is found in food often as phosphatidylcholine (aka lecithin).  Phosphatidylcholine is present in egg yolks, meat products, soy, brussel sprouts, broccoli, beef liver and more.  

During pregnancy, a great amount of choline is concentrated in the growing baby.  By the time he is born, his blood choline concentration is 3 times higher than Mom's!  Clearly, pregnancy is a critical time for choline availability.  Taken to an extreme, choline deficits can lead to neural tube defects in the embryo as well as cognitive impairment.  

According to Dr. Caudill, the author of the article being referenced here, "the majority of pregnant (and presumably lactating) women are not achieving the target intake levels and that certain common genetic variants may increase requirements for choline beyond current recommendations."

Ideas like this show us we have a long way to go if we want to truly provide comprehensive prenatal care.

Massage- Real Benefits

Most people enjoy receiving massages.  But in recent years, massage therapy has been gaining steam as a legitimate therapeutic modality.  Beyond rubbing muscles to make you "feel good" for an hour, it is very likely that there are discernible biological changes that occur as a result of a good massage.

The New York Times reported on a recent research article that highlights some of the benefits of massage therapy.  It appears that volunteers had lowered cortisol levels after a massage compared to controls. Cortisol is regarded as the "stress hormone" that often runs out of control in our lives. In other words, massage lowers stress levels.  This may not be a surprise, but it is good to see that our this effect is more than psychological; it actually changes our biochemistry.

It also "decreased IL-4, IL-5, IL-10, and IL-13 levels relative to baseline measures."  Interleukins (IL) are chemicals that cells in your body use to talk to each other.  Many are produced by immune cells.  A decrease in these levels is interpreted as a generally good thing in this context.  We want cells in your body to talk to each other, not scream at each other.

Dr. Mark Hyman Rapaport, the lead author of the study is quoted as saying the findings are “very, very intriguing and very, very exciting — and I’m a skeptic.” 

Massage therapy probably won't replace regular visits to your doctor, but it may deserve as place alongside "healthy diet & regular exercise" as staples of a healthy lifestyle.

Stress and epigenetics

I've written previously on the concept of epigenetics, the study of gene expression.  We know that for all intents and purposes, your genes do not change.  However, the little signals that tell your body when to express those genes (epigenetic signals) can be altered.  Food certainly has a powerful role in this although we do not understand all the details.  A recent paper also demonstrates that chronic stress will alter epigenetic markers.

Researchers at the Johns Hopkins School of Medicine found that the markers on genes were different after mice were exposed to stress hormones.  They believe that this may have a significant role in the development of  mood disorders.  Notably, the changes were found to be long lasting.  The epigenetic changes were presents for weeks even after the hormones had been removed from their environment.  In other words, these are potentially long lasting epigenetic changes.

 

"These behaviors, which were probably advantageous earlier in evolution, aren't as useful today with modern stressors that we can't fight or flee, such as work deadlines, Potash adds. Consequently, chronic stress might instead lead to depression or other mood disorders triggered by epigenetic changes."

I spend a lot of time talking about the benefits of eating good food.  But total health requires a life style adaptation as well.  Some people believe they thrive when under pressure; we even take pride in it.  Nobody can argue that some individuals genuinely do well under chronic stress. However, we must understand that your performance (at your job, school etc.) does not necessarily correlate with your well-being.  Chronic stress comes with a price.  Much of it has been well described (HPA dysfunction, hypercortisolemia etc.) We now have evidence that even your DNA expression may be altered by stress.

A Doctor to Listen To

Dr. Preston Maring was featured in the New York Times in a piece discussing his activism in bringing good food into the health care setting.  We've all been a part of a conversation that went something like this, "yeah yeah yeah.... I know I know... eating well is important.." as we shrug our shoulder and move on with our lives. 

Many doctors will say with their mouth, "nutrition is important" but not really believe their own words.  If anything, they believe it 'just a little bit' as they continue to eat fast food dinners and vending machine snacks.

From the article:

Dr. Maring, 64, a gynecologist and obstetrician with three decades as a surgeon, is well known as a former physician in chief at the hospital... But increasingly, his reputation and perpetual motion revolve around his conviction that in the health professions, the kitchen must become as crucial as the clinic. Food is at the center of health and illness, he argues, and so doctors must make all aspects of it — growing, buying, cooking, eating — a mainstay of their medical educations, their personal lives and their practices. 

I agree with him 100%.  The kitchen must absolutely be as crucial as the clinic (in the management of any disease).  In the prevention of chronic disease, it may be the most important place in your world.

Garlic and immune activity

I just saw an advertisement for flu shots at the local pharmacy.   I wanted to remind readers that in addition to conventional methods, tweaking your diet can go a long way in helping prevent colds and flu this season.

Garlic has long been used as a delicious addition to our foods.  But it has also served medicinal purposes.  Garlic is known to have antimicrobial and antiviral properties.  It carries with it a long list of fancy-sounding compounds like:

(allicin, alliin and agoene), volatile oils, enzymes (allinase, peroxidase and miracynase), carbohydrates (sucrose and glucose), minerals (selenium), amino acids such as cysteine, glutamine, isoleucine and methionine ... bioflavonoids such as quercetin and cyanidin, allistatin I and allistatin II, and vitamins C, E and A which help to protect us from oxidation agents and free radicals, and other vitamins such as niacin, B1 and B2 and beta-carotene.

Here's a simple way to prepare garlic in the oven.  You can spread this roasted garlic over crackers or toast for a delicious snack.  Or roast some brocooli and peppers and serve together.  Roasted garlic can be used in all kinds of dressings or sauces.

As we're in back to school season (with runny noses and shared germs), this can be yummy way to help your immune system.

Vitamin D and Pregnancy

Another paper on the significance of vitamin D has recently been published.  In it, the authors report,

"low maternal levels of 25 hydroxyvitamin D are associated with adverse outcomes for both mother and fetus in pregnancy as well as the neonate and child."

Further, low vitamin D seems to be linked with "infertility, preeclampsia, gestational diabetes and an increased rate of caesarean section."

Clearly, it is very important for pregnant women to maintain healthy vitamin D levels.  The general recommendation for most people is to maintain serum 25-OH D levels above 55 ng/mL.  The absolute bottom threshold seems to be around 33ng/mL but greater than 55 is generally believed to be a more optimal range.  

The authors of this study admit that whether low vitamin D causes problems during pregnancy or is simply associated with them is unclear.  However, they also acknowledge that there are plausible physiological mechanisms that could explain how low vitamin D would cause the issues.

With 3/4 of American deficient in vitamin D, it appears that we need to pay special attention to pregnant mothers.

Economic burden of diabetes

A new report published indicates that 23% of hospital stays involve a patient with diabetes.   Diabetics racked up a total of $83 billion dollars in hospital fees.  These patients were in the hospital for longer periods than individuals without diabetes, costing nearly $2,200 more per stay.  

If $83 billion dollars in hospital bills seems high, consider this; the total cost of diabetes related care is over $218 billion dollars per year.  Couple this with the knowledge that the vast majority of diabetes is preventable.  It is a result of poor diet and lifestyle.

More on AGEs

You may have heard of many people taking a baby aspirin daily to "thin the blood."  This "thinning" effect is accomplished by shutting down the function of platelets; cell fragments involved in blood clotting.  The AGEs mentioned in the previous post negatively affect platelets.

This study shows that when albumin is glycated, it can activate platelets.  These activated platelets can then go on to promote heart disease.

Additionally, AGEs have also been implicated in degenerative joint disease.  AGEs may collect in joint cartilage to promote the wear and tear typical of osteoarthritis.  By now, you can see that diabetes can wreak quite a bit of havoc through the production of AGEs alone.

Diabetes- AGEs

Another harmful factor generated in diabetes are products called 'advanced glycation end-products', or AGEs.  AGEs develop essentially when proteins in your body (or fats or other compounds) are tagged with a sugar molecule.  While this may see relatively harmless, we must understand that a central tenant in biology is that "form dictates function."  When we add sugar residues, we have changed the form of that molecule.  That will invariably lead to an alteration in function.

These AGEs can go on to make blood vessels stiff (not a good thing), generate free radicals and promote inflammation.  If all of that sounds a little to "science-ey" for you, then how about this;  AGEs also make your skin age.

AGEs are often discussed outside of the context of diabetes.  While they can be generated in our body, we also consume them in our diet.  Diet sodas are a common source of AGE consumption because of the aspartame and caramel colourant.  Animal derived foods with lots of fat and protein are another common source of AGEs.

While we always have some level of AGE production, exogenous intake and extraordinary production during diabetes promotes pathogenic processes.  In fact, doctors often monitor a patient's A1C, a marker of glycated end products, to determine how well blood sugar management has been over an extended period of time. 

In summary, diabetes produces AGEs.  AGEs then promote more insulin resistance (with oxidative stress and inflammation) that exacerbate the diabetes.    Then we make more AGEs.... and the vicious cycle goes on and on.

Diabetes- Avandia

Avandia, a medication used to increase insulin sensitivity, has taken a lot of heat over the past several weeks.  This popular diabetes medication has made headlines because of the increased risk of heart attacks and strokes associated with it.  The matter is far from over.  As of today, the FDA is still considering whether or not to pull Avandia from the market.

When these matters are debated, you often find two camps where one group strongly supports the use of a drug while the other group is staunchly opposed.  Both perspectives are often rooted in the naive idea that "drugs are amazing" or "drugs are evil."

Individuals in the natural health community, like myself, are often guilty of decrying the multiple adverse effects of medications and the overuse of these powerful tools.  This leads to the well intentioned but ill informed opinion that "drugs are evil."  News like this can serve as a sort of vindication for anti-drug advocates.

But consider the broader view here.  Medications clearly save lives and improve the quality of life for millions of people in the U.S.  I read this piece in the LA Times which is a bit more fair and balanced than many viewpoints. 

With any medication, you will help some people and hurt others.  It is impossible for a drug to be everything to all people.  

"It's always a balancing act for us," said Karen Riley, a spokeswoman for the Food and Drug Administration. "Products get approval because we see that the benefits outweigh the risks. Then we try to adjust as we go along." LA Times July 1, 2010.

Our natural tendency is to assume that "the powers that be" have clearly determined that the benefits outweigh the risk.  The case of Avandia is evidence that this is a dangerous assumption.  Consider the recalls we hear daily; McDonald's toys, Toyota cars, cribs, baby bottles and more.  Drugs are no different. 

Diabetes- Inflammation

The risks of diabetes are well known.  Individuals run the risk of kidney failure, blindness, poor wound healing, loss of limbs & nerve damage.  As blood sugar is chronically elevated, a number of other physiological events occurs simultaneously. We'll start this series off discussing chronic inflammation.

A rise in blood sugar alone can be problematic enough by itself.  But it appears that with hyperglycemia, diabetics also experience inflammation.  This inflammation also promotes damage to the eyes, kidneys and nerves.

"In general, hyperglycemia is the main initiator of diabetic retinopathy, nephropathy, and neuropathy, and it participates in the development of diabetic cardiovascular diseases. Although the precise role of inflammation in the development of diabetic microvascular diseases is still unclear, it is likely that inflammation induced by diabetes and insulin resistance can accelerate atherosclerosis in patients with diabetes."  J Periodontol 2008 Aug;79(8 Suppl):1527-34.

Inflammation itself has been implicated in many, if not most, chronic diseases.  Take a look at this article that discusses how peripheral inflammation (away from the brain), can actually damage brain cells!

"As a consequence of excessive inflammatory response triggered by pro-inflammatory cytokines in the periphery, free radicals, oxidants and glucocorticoids are over-produced, which can affect glial cell functions and damage neurons in the brain. Indeed, decreased neurogenesis and the dysfunction of neurotrophic system (up- or down-regulations of neurotrophins and their receptors) have been recently found."  Prog Neuropsychopharmacol Biol Psychiatry 2010 Jul 2. [Epub ahead of print]

There's no doubt that with hyperglycemia, we set off on a downward spiral of multiple physiological systems.  While convenient, it is overly simplified to understand the risks of diabetes as being secondary only to high blood sugar.  High blood sugar assaults your body directly, but then promotes inflammation that will also assault your body.  This is a proverbial "double whammy."

Before continuing on with the next posts, let's consider this.  Do you believe that the pathophysiology of diabetes provides a "double whammy?"  Or is it a "triple whammy?"  "Quadruple whammy?"  

Lots of things go wrong.  This is the tip of the iceberg. 

Diabetes

Approximately 24 million Americans suffer from diabetes.  It sucks up $116 billion dollars each year in direct medical costs and $58 billion dollars a year in indirect costs.  More than 90% of diabetics are considered type 2 diabetics, or non-insulin dependent.  There are ever changing medications used to manage diabetes, many of which dramatically help an individual manage blood sugar, but ultimately fall short in correcting a person's physiology.

In the next series, we'll take a look at how diabetes works and why this crippling disease can be almost entirely prevented.  Most of us probably know at least one diabetic in our inner circle of family and friends.  To some, it seems inevitable because of a defeatist attitude that echoes, "my mom had it and so I'll get it too... it's in my genes."  We'll zoom in and look at the vicious chain of degeneration that diabetes sets off.  Then, we'll look at natural means to manage this disorder.

Many people know something about diabetes.  But the reality is; it's much worse than you think.

Vitamin D and Autism

Vitamin D deficiency is rampant in the United States.  Approximately 75% of the population has low levels of vitamin D.  The list of associated illnesses is growing; heart disease, chronic pain, multiple sclerosis etc.  One more disease on the list may be autism.

There is nothing near conclusive data on this, but many researchers recommend higher doses of vitamin D for affected individuals.  Maintaining healthy vitamin D levels is good counsel to all of us, but considering the often aberrant immune response in autistic kids, this may be especially relevant.

While autism and something like multiple sclerosis may seem to be dramatically different diseases on the surface, there is a common thread.  That commonality is the fact that the immune system may be overzealous in response to poor nutritional/biochemical modulation, environmental insult, or some combination of the two. 

Supplementing with vitamin D is not likely to be the 'cure' for autism.  But it may play a significant role in the prevention and the reduction of symptoms.

Brain and Cholesterol

In the old days, high cholesterol was a very scary thing.  High cholesterol meant that your arteries had a very good chance of getting plugged up down the road.  With that, a heart attack or stroke was not far behind.  As scientists learned more about physiology and realized that half the people who died of heart disease had normal cholesterol, we learned that there's more to the story of heart disease than just cholesterol.

It's important not to throw our understanding of cholesterol completely out the window.  Does it play a major role in heart disease?  The safe answer is probably, "in some people 'yes'...but in others, 'not as much.' "  With that, a new study shows a direct link between the brain and cholesterol levels.  In fact, they authors quote,

"Our data suggest that a neural circuit in the brain is directly involved in the control of cholesterol metabolism by the liver."

To put it in perspective, a statement to the media said, "We have long thought that cholesterol is exclusively regulated through dietary absorption or synthesis and secretion by the liver.... our study shows for the first time that cholesterol is also under direct 'remote control' by specific neurocircuitry in the central nervous system." 

Pretty remarkable stuff; I think it's time that your cardiologist, nutritionist and neurologist (at the very least) get together to figure out the best way to keep you healthy.

Sugary Drinks and Blood Pressure

Sugary drinks are terrible stuff.  They increase the risk of diabetes, obesity and are nutritionally bankrupt.  A new study shows that it may also increase blood pressure.

This article states that the average American drinks 2.3 sugary beverages per day.  This is in addition to the  sugar we take in our cookies, pies, cakes and the refined carbohydrates in our white breads, pastas and other treats.  Lowering sugar intake cut both diastolic and systolic readings in participants.

While the total decline in blood pressure isn't mind-blowing, keep in mind that cutting sugar consumption will also decrease weight, decrease inflammation, help manage insulin resistance and a host of other things that one wouldn't directly related to blood pressure.  Taken as a package, it seems a good idea to drop the sugary beverages.

Soda Tax

I've written about a so called, "fat tax" in previous posts.  Another concept thrown around every few years is the idea of a "soda tax."  Proponents argue that taxing sodas approximately 1 cent per ounce would "kill two birds with one stone."  First, it would raise much needed revenue.  Second, it would potentially decrease soda consumption and improve the health of individuals in that area.

While there has been some debate on the efficacy of a soda tax, it's been in the news recently as Washington DC recently wrestled with the idea of implementing a soda tax within the district.  

I read this Wall Street Journal blog recently that shared some good information and wanted to pass it along.

More Bad News

News released today that nearly 50% of American adults have high blood pressure, diabetes, or high cholesterol.  All 3 of these are bad in and of themselves, but also strongly predispose to heart disease, the leading killer in the United States.

Dr. Steve Nissen from the Cleveland Clinic is quoted as saying, "These findings are disturbing and reflect the cumulative effects of the modern American lifestyle."

Our inattentiveness to healthy diets, lack of exercise and general disregard for our personal health is taking a toll. Where will we be a generation from now?

Bad News About School Lunches

Is our overweight problem a threat to national security?  A group of retired military officers state that school lunches are so unhealthy, they are making future soldiers "too fat to fight."  Currently, 27 million young adults are deemed too fat to serve in the military. 

Let's remember that these fat kids become fat adults.  Our current health crisis starts with overweight and sick kids.  We are setting ourselves up for a dangerous future.

Environmental Hazards

Last week, Time magazine did a great piece on chemical dangers in the environment.  This comes a few months after the FDA expressed concerns over the safety of bisphenol A (BPA), a compound found in many plastics.   The concern is especially grave for unborn children as reports have shown that BPA crosses the placenta.

There are toxins everywhere.  We'll do a short series on these chemical compounds, the sources and what we can do about them. Browse through the Time magazine article as it gives a good primer on this important topic.

Folic Acid

Several studies in the past have shown a risk in taking folic acid, the synthetic form of folate.  Folate is a B vitamin found in green vegetables.  Folic acid, on the other hand, is a synthetic form that is used in most multivitamins.  It is also used to fortify many cereals and grains.

This article references a paper that found an increased risk of breast cancer with additional folic acid consumption.  Folic acid also made headlines a few weeks ago as a link between its use and colon cancer was also described. 

Be cautious of overdoing it with synthetic supplements.  Food sources are always best.

Infants and Vitamin D

The American Academy of Pediatrics increased their vitamin D recommendations for infants in late 2008.  A recent report in Pediatrics takes a look at how we're doing. The answer is; bad.  The vast majority of infants still do not get adequate amounts of vitamin D.

Pregnant moms should make sure their vitamin D levels are on the high end of normal.  Mom should make sure her vitamin D levels are high while she is nursing her infant.  And infants should also be given supplemental vitamin D.

Maternal Diet and Chronic Disease

A recent review article was published in the Journal of Nutrition.  In it, the authors state, "Micronutrient status in fetal and early life may alter metabolism, vasculature, and organ growth and function, leading to increased risk of cardiometabolic disorders, adiposity, altered kidney function, and, ultimately, to type 2 diabetes and cardiovascular diseases."

This means mom's nutrient deficits have potential to create long term harm in the child.  By now, this kind of research shouldn't be surprising.

Up until recently, most prenatal nutrition recommendations were relatively boiler-plate.  Get enough folic acid to prevent neural tube defects and take a fish oil capsule.  Some advised women to avoid fish due to mercury contamination and many experts even spend the effort to figure out how much coffee women can "get away with" without long term negative effects.

But rather than thinking about how "not to hurt" the developing child, it is time we focus on providing him/her the best chance for long term health and wellness.

Will Your Child Develop Metabolic Syndrome?

Metabolic syndrome is a major problem in the United States.  It is marked by insulin resistance, inflammation, dyslipidemia, hypertension and a number of other variables.  Within the past 10 years, the prevalence has risen dramatically among adolescents.  Over 45% of adolescents have at least 1 risk factor for metabolic syndrome and with overweight and obesity on the rise, this number is likely rise.

A recent study in Diabetes Care found that hyperinsulinemia in pregnant women predicted an increase in overweight and metabolic syndrome in the offspring!  

Other researchers propose that changes in the nutritional environment of the pregnant mother may lead to "a long term re-setting of cellular energy homeostasis, most probably via epigenetic modification of genes involved in a number of key regulatory pathways."  In other words, the genes themselves may not change but mom may profoundly influence the expression of the child's genes.  This doesn't suggest that the health of the child is now predetermined.  But it does tell us that your child has now been, "dealt a bad hand."  Nat Rev Endocrinol 2009 Nov;5(11):604-10. Epub 2009 Sep 29.

"Eating for two" should take on a different light now.  The abuse of chocolate cake and twinkies will forever affect your child.