This Is MS Multiple Sclerosis Community: Knowledge & Support

Dr. Patrick Woods is the Scientific Director of the Fibromyalgia Association of America. His findings in fibromyalgia are low dopamine, low iron, spinal cord changes and dysautonomia (autonomic nervous system dysfunction). As we have seen, MS has the same findings. According to the Lupus Foundation of America, in about half of those with lupus, the disease attacks the brain and spinal cord. Science has not yet been able to provide an explanation for this. We have explained the low dopamine, low iron, and dysautonomia. Now we will need to explain the spinal cord changes. According to the National Institutes of Health, subacute combined degeneration of the spinal cord is CAUSED by a vitamin B12 deficiency. Here is some information from the NIH website.

"Subacute combined degeneration primarily affects the spinal cord but its effects on the brain and the peripheral (body) nerves are the reason for the term “combined”. At first, the disease damages the covering of the nerves (the myelin sheath). It later affects the entire nerve cell.

Symptoms
Symptoms include:

•Abnormal sensations (tingling and numbness)

•Weakness of the legs, arms, or other areas

These symptoms slowly get worse and are usually felt on both sides of the body.

Other symptoms include:

•Clumsiness, stiff, or awkward movements

•Change in mental state such as memory problems, irritability, apathy, confusion, or dementia

•Decreased vision

•Depression

•Sleepiness

Unsteady gait and loss of balance

Do fibromyalgia patients lack B12?

A study published in the Scandinavian Journal of Rheumatology found that fibromyalgia and CFS patients had low B12 and resulting high homocysteine in their cerebrospinal fluid. Here is the conclusion from the study.

"In conclusion, this study provides convincing preliminary evidence that high homocysteine levels in cerebrospinal fluid homocysteine is an underlying factor in patients suffering from Fibromyalgia and Chronic Fatigue Syndrome. Low vitamin B12 levels in cerebrospinal fluid and possibly low SAM levels are implicated as contributing factors. Additional evidence from other studies further support the idea that deficiencies in enzymatic pathways in the brain involving vitamin B12 , homocysteine, and folic acid underlie a range of neurological disorders. Deficiencies in these essential biochemical pathways in the brain should be considered by health practitioners in the evaluation of successful interventions for reversing symptoms of Fibromyalgia, Chronic Fatigue Syndrome, and other neurological conditions." (Regland,1997)

The lack of vitamin B12 in fibromyalgia also explains the other missing neurotransmitter needed to regulate the autonomic nervous system. We know dopamine is needed for adrenaline, one of the neurotransmitters. Fibromyalgia and MS patients lack dopamine. The other neurotransmitter is acetylcholine. Vitamin B12 and folate are required for the synthesis of choline, before becoming acetylcholine.



In the coming posts, we will look closely at the association between MS and vitamin B12 and also identify how a lack of protease would lead to a B12 deficiency.

If another condition or disease commonly occurs with any of the diseases we have been discussing (no matter what it is), then we should be able to trace it back to missing protease as well.

One of these commonly occurring conditions would be restless legs syndrome (RLS). Here is some information on its association with MS.
http://ms.about.com/od/signssymptoms/a/ ... s_legs.htm

In the study entitled, "Systemic Lupus and Risk of Restless Legs Syndrome", the conclusion states, "These novel data indicated that RLS is more prevalent in women with SLE than in controls."

And in an article from Arthritis Today, entitled, "Restless Leg Syndrome Linked to Fibromyalgia; A study finds these two conditions commonly overlap," it is stated that RLS occurs in 33 percent of those with fibromyalgia.

We have shown why a lack of protease would lead to a lack of iron and dopamine. The following study entitled,"Dopamine and iron in the pathophysiology of restless legs syndrome (RLS)", makes the connection to RLS and a lack of dopamine and iron. Here is the conclusion from the study. "It is concluded that there may be an iron-dopamine connection central to the pathophysiology of RLS for at least some if not most patients with this disorder".


http://www.ncbi.nlm.nih.gov/pubmed/15222997

It has long been assumed by many that a virus or some form of bacteria is the causative factor behind many of these diseases. None more so than in CFS perhaps. After many years of controversy, recent very definitive spinal fluid studies in CFS, fibromyalgia and Gulf War Syndrome (GWS) were unable to find a bacterial, viral, or genetic connection to any the diseases.

Here is what Suzanne Vernon, the scientific director of the Chronic Fatigue and Immune Dysfunction Syndrome Association of America said about these recent findings. "I'm very excited about this-you can't dispute these biological findings." These findings were reported on in the Feb. 23, 2011 Wall Street Journal. They stated, "Schutzer (lead researcher) is also involved in a separate study looking for microbes-including the virus XMRV in the fluid of 43 CFS patients. An abstract published earlier this month in Annals of Neurology reported that the team was unable to find XMRV in the spinal fluid of the CFS patients."

What they did find,though,will give us direct evidence of what we believe is the cause of these illnesses. We will explore these findings in the next post. There is a connection to bacteria, viruses and proteases however, and this will explain why many sufferers say their disease was preceded by a viral or bacterial infection.

Proteases (which digest proteins) are responsible for keeping the small intestine free from parasites (such as intestinal worms), yeast overgrowth, and bacteria etc. Parasites, fungal forms, and bacteria are proteins that additionally disguise themselves in a protein sheath that our bodies view as normal. Proteases work by removing this protein shell. With the protective barrier down, your immune system can destroy the invading organism. If you are bordering on a pancreatic enzyme deficiency, and you contact a viral or bacterial infection, this would deplete your protease, as they would be needed to 'disarm' the invader.

Suzanne Vernon also stated about these spinal tap studies, "They looked at a really important fluid, using really advanced technology.." So, not only should these studies to able to rule out things like the XMRV virus, they should be able to shed some definite light on the actual disease process involved. And indeed they do. Following are the findings from these spinal tap studies.


■two proteins suggesting a protease – antiprotease imbalance is present. This implicates increased production of elastase, an enzyme Dr. De Meirleir believes plays a role.

■several proteins suggesting small amounts of bleeding in the brain could be caused by the aggregation of proteins (amyloids) in the blood vessels.

■Another protein suggests increased free radical production is present.

■Another suggests that problems with the vasoconstriction of the blood vessels and damage to the cells lining the blood vessels (the endothelial cells).

■Another protein is associated with inflammation.

■One protein suggesting altered rates of cell suicide (apoptosis) are present. (Johnson,2010)

As the first finding shows, protease are implicated in the disease process of CFS, fibromyalgia and GWS.
The second finding implicates amyloids. Amyloids are misshapen proteins. If you are unable to break down dietary proteins, you would not be able to form normal proteins. Amino acids that come from dietary proteins are the building blocks for body proteins (factors in the blood and tissue).

The remaining protein findings will be clearly explained as we move forward.

We will look at one more spinal tap study on CFS, fibromyalgia, and PGI for additional clues. In spinal tap studies conducted at the Georgetown University Proteomics Laboratory Division of Rheumatology, Immunology & Allergy, researchers concluded, "This pilot study detected an IDENTICAL set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohors of subjects with overlapping CFS, PGI, and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanisms may be shared," (Baraniuuk, 2005).

We have shown that CFS, fibromyalgia, MS etc. share many of the same features which define these diseases, such as spinal cord degeneration, autonomic dysfunction, low adrenal and thyroid hormones etc. The researchers concluded from the spinal tap study that even though CFS, PGS, and fibromyalgia had different names, based on the evidence from the studies, they may in reality all originate from the same source. We have shown that the symptoms we have presented, so far, of all of these diseases can be traced back to missing pancreatic enzymes. As can the evidence from the spinal fluid studies.

So what would have determined whether a person would have received a diagnosis of CFS versus fibromyalgia or PGS? If a patient went to a doctor and presented with the symptoms we have been discussing and had just returned from the Persian Gulf War, I would expect this to influence the diagnosis. Also, if a patients primary complaint was muscle pain and his fatigue was not as predominant, he may be given a diagnosis of fibromyalgia versus CFS. Of course, the type of doctor and other factors could come into play as well. So, it may well be that the severity and predominance of symptoms is a major factor in what determines a diagnosis.

What about MS? Is the diagnosis of MS made, in part, on the presence of white matter lesions? Is this what tips the scales to a diagnosis of MS, since we have shown so far many of the symptoms and findings to be the same? What if white matter lesions are part of the disease process of CFS, Sjogren's and lupus as well and they were just not tested for or present yet at the time of diagnosis? Following are studies that confirm the presence of white matter lesions in the other diseases we have been discussing.

White matter lesions in lupus: http://www.na-mic.org/pages/DBP:Lupus

White matter lesions in CFS: http://bjp.rcpsych.org/content/167/1/86.abstract

White matter lesions in Sjogren's: http://www.ncbi.nlm.nih.gov/pubmed/10381047


We still have much more evidence to present. We will show that all of these diseases have mitochondrial dysfunction, improper glucose metabolism, elevated tumor necrosis factor, a disruption in the heme biosynthetic pathway and the cytochrome P450 enzyme system, endothelial cell dysfunction and much more. And we will be able to trace all of these findings directly back to protease.

Both of the spinal tap studies in CFS and fibromyalgia identified amyloids (improperly folded proteins). These amyloids also exist in lupus, rheumatoid arthritis, and Sjogren's. This is called secondary amyloidosis. There is also a disease called primary amyloidosis. According to Mayo Clinic, these amyloids can build up in the heart, kidney, liver, spleen, nerves, skin, blood vessels, and gastrointestinal tract. Here are some of the symptoms-irregular heartbeats, numbness, shortness of breath, swelling, and weak grip. It can also lead to endocrine failure, as well as heart, kidney, and respiratory failure. These diseases all share many of the same symptoms because they have the same abnormal proteins or amyloids.

In the abstract entitled, "Secondary Amyloidosis Associated with Multiple Sclerosis," it states, "These data suggest that MS is related to secondary amyloidoisis.."


In the article entitled, "Why Do I Keep Having to Scratch? Fibromyalgia and the Sensation of Itching" the author states in the last sentence, "Surprisingly, the fact that certain FMS patients tend to itch a lot just scratches the surface (no pun intended) of quite a number of situations unique to FMS." Of course, we know that itchy skin is also a symptom of MS. And now one that will no longer be a mystery.

As the following study entitled, "Proteinase-Activated Receptor-2 Mediates Itch: A Novel Pathway for Pruritus in Human Skin" shows, protease play an important role in this symptom as well.

http://www.jneurosci.org/content/23/15/6176.full

Many of the diseases we have been discussing have been found to have increased pain sensitivity. For instance, in the study entitled,"The relationship between fibromyalgia and interstitial cystitis," it states,"These data suggest that IC and fibromyalgia have significant overlap in symptomatology, and that IC patients display diffusely increased nociception (pain sensitivity), as seen in fibromyalgia. Although central mechanisms have been suspected to contribute to the pathogenesis of fibromyalgia for some time, we speculate that these same mechanisms may be operative in IC, which has traditionally been felt to be a bladder disorder." (Note that these researchers also feel that both of these diseases may share a common source)

Endorphins and enkephalins are the body’s natural painkillers. The word “endorphin” is used generically to describe both classes of painkillers. Endorphins are morphine-like substances that block pain signals in the spinal cord and brain stem. They do this by binding to the same receptor sites that pain signals use.

The body’s goal in pain suppression is to allow the body to cope with pain while remaining focused, rather than allowing the perception of pain to overwhelm the system and cause panic and confusion. Endorphins are released by the brain and central nervous system when the brain perceives pain. They dull the sensation of pain and also help the individual cope with the emotional aspects of pain by changing the way the pain is perceived. Since endorphins can influence perception, they also play a role in memory formation and mood.

Studies show that the diseases we have been discussing have lower levels of endorphins than normal. For example, the study entitled, “Decreased immunoreactive beta-endorphin in mononcuclear leucocytes from patients with chronic fatigue syndrome,” found that endorphin levels were “significantly lower” in chronic fatigue syndrome patients than in healthy subjects. In fact, one of the drugs used to treat multiple sclerosis, fibromyalgia, etc. is the opiate antagonist low dose naltrexone (LDN). It was initially approved by the FDA to treat heroin addiction. Low doses of naltrexone are thought to work by temporarily blocking the body’s ability to release endorphins by binding to the same receptor sites. The body compensates by producing more endorphins than it typically would once the drug wears off. If you lack the ability to make endorphins though, this accelerated response could just further deplete your body’s long term ability to produce endorphins.

The body makes two classes of endorphins, or enkephalins, from amino acids found in high protein foods. One form of enkephalin contains leucine, and the other contains methionine. The other amino acids found in both types of enkephalins are phenylalanine and tyrosine. We have shown that MS patients lack these specific amino acids.

Phenylalanine and tyrosine are also needed to produce "an essential cofactor involved in mitochondrial oxidative phosphorylation as well as a potent antioxidant". The quote is from the following abstract entitled, "Coenzyme Q10 Effects in Neurodegenerative Disease".

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785862/

CoQ10 is a fat-soluble compound synthesized by the body and also consumed in the diet. A report from Iowa State University lists beef, chicken, pork, and fish as the foods with the highest levels of CoQ10. In a healthy person, CoQ10 can be synthesized, but it requires the presence of one of two amino acids we have found lacking in CFS, fibromyalgia, MS etc.; phenylalanine or tyrosine. The Linus Pauling Institute at Oregon State University states, "The biosynthesis of coenzyme Q10 involves three major steps: 1) synthesis of the benzoquinone structure from either tyrosine or phenylalanine." Tyrosine is derived from phenylalanine, and phenylalanine is found in high protein foods. Without the ability to break down high protein foods, you would not have the necessary amino acids to produce CoQ10.

The inability to break down high protein foods would also account for another one of our missing nutrients-zinc.
Here is some information on foods that contain zinc. As the information states,"Zinc is very much associated with protein foods. Thus, you may assume that most foods high in zinc are protein-rich as well. The best sources of zinc include beef, lamb, pork, crabmeat, turkey, chicken, lobster, clams and salmon."
http://www.nutritional-supplements-heal ... urces.html

The other diseases we have been discussing lack zinc as well. This study entitled, "Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS" states, "These results show that CFS is accompanied by a low serum zinc status.."
http://www.ncbi.nlm.nih.gov/pubmed/16338007

Tumor Necrosis Factor (TNF) is responsible for many of the symptoms associated with these diseases. What is TNF? TNF is a cytokine. It is a normal, necessary part of our immune systems, but it becomes elevated or dysregulated in the diseases we have been discussing.

According to an article in Molecular Psychiatry, "TNF has long been implicated in the immunopathogenesis of Multiple Sclerosis (MS), which is an inflammatory and demyelinating disease of the central nervous system. In MS, the magnitude of the elevation of TNF in cerebrospinal fluid mirrors the severity of the disease," (Finsen, 2002)

Studies show that lupus, CFS patients etc. also have dysregulated TNF. Here is the title to one such study. "Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelation with cellular sources and patterns of soluble immune mediator expression."

The arthritis and Crohn's disease drug Humira was designed to target TNF. The Humira website states, "Many patients with Crohn's disease produce too much of a protein called tumor necrosis factor (TNF) in their body. This excess attacks the intestines and other parts of the gastrointestinal tract, and can cause them to become inflamed. This can result in the pain, diarrhea, and other symptoms of Crohn's disease. Humira belongs to a class of biologics known as TNF blockers." Locally, TNF can cause heat, redness, swelling and pain-as seen in joints affected by arthritis.

TNF acts on the hypothalamus to generate fever and suppress appetite. TNF also kicks off a process called an "acute phase response." This can show up in your bloodwork as elevated CRP or C-Reactive Protein. It can also cause insulin resistance.

It is responsible for the feelings of malaise and flu-like symptoms that many of the sufferers of these diseases often feel, even if there is no infectious agent present. Symptoms such as sore throat, swollen glands, and low grade fevers are due to TNF. Excess circulating TNF in the bloodstream can also cause night sweats.

Recurrent apthous ulceration (RAU) or canker sores, is a common occurrence in these diseases. The abstract, "Salivary interleukin-6 and tumor necrosis factor in patients with recurrent aphthous ulceration," states, "Recurrent apthous ulceration (RAU) is a well-known oral disease which seems to be mediated principally by the immune system." The researchers found significant differences in salivary TNF between healthy controls and patients with acute RAU.

So, what is responsible for regulating TNF and degrading it when necessary? The first study title shows that the degradation and inactivation of TNF is performed by PROTEASE. It states, " Our study demonstrates degradation and inactivation of TNFalpha by pancreatic proteases..."

"Degradation and Inactivation of Plasma Tumor Necrosis Factor-alpha by Pancreatic Proteases in Experimental Acute Pancreatitis."

This next study entitled," Neutrophil Serine Proteases Fine-Tune the Inflammatory Response", states, "Studies over the past several years indicate that neutrophil serine protease may also be KEY REGULATORS of the inflammatory response." It also states, " Neutrophil serine proteases specifically process and release chemokines, CYTOKINES, and growth factors, thus modulating their biological activity."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440796/

Low levels of Human Growth Hormone (HGH) are also found in lupus, fibromyalgia, CFS, MS etc. This would need to be explained as well. The following abstract entitled, " Growth hormone and insulin growth factor-1 levels in plasma and cerebrospinal fluid of patients with multiple sclerosis" explains that HGH has a "direct influence" on myelination. It is factors such as this that explain why even though all of the deficiencies and symptoms originate with the lack of protease and DNase 1, each of us will still have varying levels of neurotransmitters and hormones based on dietary habits, medications, duration of illness etc. For this reason, some of us will be able to repair myelin damage much quicker than others, as the abstract explains. http://www.ncbi.nlm.nih.gov/pubmed/16386830

Human growth hormone or somatropin is the most abundant hormone produced by the pituitary gland and the body's most important anti-ageing hormone. HGH stimulates growth, cell reproduction, and regeneration. It is essential for normal muscle metabolism and repair. HGH also regulates the amount of sugar in the blood and promotes the break down of fat.

After failing to see an improvement in her patients with chronic fatigue syndrome after supplementation with HGH, Dr. Sarah Myhill, a CFS specialist stated, "My guess is that low levels of HGH is a symptom CFS and correcting the underlying causes of CFS will result in HGH levels returning to normal." (I agree with this)

Many people believe that as we age the amount of HGH in our bodies decreases. In fact, the difference generally, in growth hormone between adults and adolescents, is not due to the amount, but in the release. For instance, adequate amounts of blood protein levels will stimulate the release of HGH from the pituitary. In the study entitled, "Dietary protein restriction impairs both spontaneous and growth hormone-releasing factor -stimulated growth hormone release in the rat," researchers concluded,"These results demonstrate that lack of dietary protein 1)blunts spontaneous pulsatile GH release, 2)attenuates GH responsiveness to GRF challenge, and 3)reduces pituitary GH content and size."

The next few posts will be on vitamin B12 and the central role it plays in MS. Vitamin B12 is necessary for every cell in our bodies, so a deficiency could have far reaching and profound effects on our health. Vitamin B12 is made by organisms in the soil. We ingest B12 by eating animal proteins that were pastured. If an animal was not given access to soil, then the meat, eggs, milk or cheese will contain no B12. Most of our animals are raised on concrete, so this would be one reason why most Americans are low in vitamin B12.

According to a large study done at Tufts University, nearly 40% of the American population has B12 levels low enough to cause neurological damage. In addition, they tested the participants at a very low level-258pg/mL. Japan has set their B12 limits at 550pg/mL to 1200pg/mL. One of the reasons for this is that at approximately 500pg/mL you will see B12 deficiency symptoms such as dementia. On this basis, Misuyama and Kogoh proposed 550pg/mL and Tiggelen et al proposed 600pg/mL. The level we have set in the U.S. is approximately the level at which you see one of the most severe manifestations of a B12 deficiency-pernicious anemia. If you are in the normal range in the U.S., you have a severe deficiency, enough to cause pernicious anemia.

One surprising fact from the Tufts University study was that the participants in the study were eating foods rich in vitamin B12, but their bodies were not absorbing the vitamin. In the previous study I mentioned that found low B12 and high homocysteine in the cerebrospinal fluid of CFS and fibromyalgia patients, the study authors interpreted their findings to mean that low vitamin B12 levels in the cerebrospinal fluid may reflect disruption of the mechanism of transport across the blood brain barrier.

Numerous studies have found that MS patients are deficient in vitamin B12. The following study entitled, "Serum Vitamin B12, Folate, and Homocysteine Levels and their Association with Clinical and Electrophysiological Parameters in Multiple Sclerosis," found that like CFS and fibromyalgia patients, MS patients also had high homocysteine and low B12. The study states in the conclusion, "Thus, we found a significant relationship between MS and vitamin B12 deficiency..."

http://www.ncbi.nlm.nih.gov/pubmed/19153046

Studies show that MS patients are also unable to properly metabolize B12.

"There is a significant association between MS and disturbed vitamin B12 metabolism," states the study entitled, "Vitamin B12 Metabolism in Multiple Sclerosis."

The study entitled, "Vitamin B12 and its Relationship to Age of Onset of Multiple Sclerosis," states, "In the present communication, we report that serum vitamin B12 levels in MS patients are related to the age of onset of the disease. These findings suggest a specific association between the timing of onset of first neurological symptoms of MS and vitamin B12 METABOLISM. In addition, since, vitamin B12 is required for the formation of myelin and for immune mechanisms, we propose that its deficiency in MS is of CRITICAL PATHOGENETIC SIGNIFICANCE."

The study entitled, "Multiple Sclerosis Associated with Vitamin B12 Deficiency," also concludes, "A vitamin B12 binding and/or transport is suspected."

Here is a quote from Julie Stachowiak, Ph.D., who has MS herself. "Studies have reported a significantly higher rate of vitamin B12 deficiency in people with MS than in people without MS, which is suspected to be due to problems with binding and transport of vitamin B12. One study found low B12 levels in the cerebrospinal fluid of people with MS, although their blood levels were normal. People with B12 deficiency have destruction of both the myelin and underlying axon."

So, what is responsible for the binding and transport of vitamin B12? The next study entitled, "Cobalamin Malabsorption Due to Nonegradation of R Proteins in the Human Intestine," states,"Pancreatic enzymes and the ionic environment in the upper gastrointestinal tract are ESSENTIAL determining factors for TRANSPORT and ABSORPTION of cobalamin (B12) in man." It concludes," Absorption of vitamin B12 is dependent on the presence of appropriate pancreatic enzymes." The specific enzymes that break down the proteins that B12 is attached to are protease.

I have heard of a substance called Intrinsic Factor which is necessary for the use of a B vitamin – I thought it was B12, but I could be wrong. In this discussion of B12 there is no mention of Intrinsic Factor; could people with MS be deficient in the substance?

Yes, lyndacarol, intrinsic factor is necessary for proper absorption of B12. Here is some of what I write in my book. "Intrinsic factor consists of tiny, innumerable open-ended protein capsules that bob around the stomach acid (think Pac-Man). It is created by the stomach in the exact same shape and size required to fit a cobalamin molecule. These capsules randomly weave and bob around amid digesting food. When they bump into vitamin B12, they quickly trap it inside. snap open and shut, and transport it to the farthest end of the small intestine."

"Making protein for intrinsic factor depends on a good supply of many different amino acids that are available primarily from animal sources. If you are unable to break down proteins, then you will not be able to produce intrinsic factor."

I also have a section on hydrochloric acid, which is required in sufficient amounts for proper digestion of proteins and the release of vitamin B12 as well.

Hi Annesse,

This is all good stuff. Well done. Have you done some work on the thyroid like nuclear receptors?

Regards

Hi Scott1- The connections we have made to the thyroid and the other diseases we have been discussing are related to a lack of the thyroid hormones, thyroxine and triiodothyronine, due to a deficiency in the essential amino acid phenylalanine. This would lead to hypothyroidism. Also, we should be able to find a B12 deficiency if a disease is a symptom of PEDD (Pancreatic Enzyme Deficiency Disease).

Following are two studies showing that vitamin B12 deficiency is common in hypothyroidism. The first study shows an approximately 40% prevalence of B12 deficiency in hypothyroid patients. While the deficiencies found in these studies are remarkable, these numbers likely would have been much higher if a more appropriate set of criteria had been used. First, they tested serum (blood) levels. Cellular levels are often much lower. Second, they used an extremely low level to determine a deficiency-133 pg/mL. At more than three times that level, you will start to see disease symptoms such as memory loss, lethargy, and dementia.

The title of the first study is "Vitamin B12 Deficiency Common in Primary Hypothyroidism."

http://www.ncbi.nlm.nih.gov/pubmed/18655403

The second study is entitled,"Prevalence and Evaluation of B12 Deficiency in Patients with Autoimmune Thyroid Disease."

http://www.ncbi.nlm.nih.gov/pubmed/16969140

The study concluded that, "Patients with AITD have a high prevalence of B12 deficiency and particularly of pernicious anemia."
In pernicious anemia, red blood cells are abnormally formed due to an inability to absorb B12. According to a study entitled, Anemia in Hypothyroidism, "Pernicious anemia occurs 20 times more frequently in patients with hypothyroidism than generally," (Antonijevic, 1999).

Patients with hypothyroidism also have dysregulated glucose metabolism as do MS patients etc. I haven't posted on this quite yet.
Since this is a pathway, that begins with a lack of protease, you would also expect to find elevated tumor necrosis factor and elevated homocysteine. The first study on hypothyroidism and tumor necrosis factor states, "In patients with hypothyroidism, serum concentrations of TNF were significantly higher than those found in controls."

http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract

In the study entitled, "Homocysteine, Hypothyroidism, and Effect of Thyroid Hormone Replacement" researchers concluded that homocysteine levels are elevated in hypothyroidism.