Tuesday, March 24, 2015

Inflammation and Sulfate

Historically, people were injured or died from 1. child birth (mom or baby), 2. trauma (farm accidents, war, duels) and 3. various infectious diseases. Perinatal mortality is much improved, and People still come to the ED for trauma and infection but with modern sanitation, antibiotics, medical and surgical practices; people usually are surviving these events.

However, despite these advanced, in the last 100 years we have seen an explosion of chronic inflammatory illnesses from lupus to crohns disease, asthma, and even hypertension, diabetes, and heart disease.  Some argue that these inflammatory disorders were always there but we are seeing more of them today because people are living longer today and we are recognizing them better.

It is apparent that the current lifespan upper limit is 120 years.  However, Man rarely reaches that upper limit because of environmental factors damaging our organs and not because our organ systems are defectively designed.  According to the Bible, Man used to live up to 1000 years and ancient peoples organs also lasted this long with no mention of organ transplant.  So why are we now wearing out early?  As I see it, apart from telomerase activity and other acquired genetic corruptions, either God messed up designing us, or we are depriving and/or poisoning ourselves in some way.  It is my faith that God did not design us to wear out before our time. 

Also, many people lived to old age even during the Middle Ages.  Much of the reason for the supposed shorter life span is because the reported value averages all the babies that died at birth with everyone else.  If you survived birth, you were likely to live a long time just like today.

All these modern chronic inflammatory diseases have something in common. They all are associated with elevated homocysteine levels.  Accordingly, homocysyeine is considered a nonspecific marker of inflammation.  But, thats just it.  Homocysteine is not nonspecific. Homocysteine is a very specific biochemical intermediate in the sulfur and DNA repair pathway.  Could it be that elevated homocysteine is pointing us directly to what the problem is-- Sulfate deficiency?

Turns out that sulfate (SO4^2-) is used all over in the body for many things. It is one of the most important negative ions (anions) in the body after chloride (Cl-) and bicarbonate (CO3^2-).  Sulfate is used to make other more complex molecules more soluble.  The liver conjugates toxins and drugs with sulfate so they can be excreated by the kidney.  Similarly, many important complex molecules in the body are sulfated to increase their solubility.

You might have heard of the good cholesterol that is in egg yokes is also found in our brain.  Or you might have taken glucosamine and condroitin for your joints.  An important natural blood thinner is heparin.  However, in reality its not just cholesterol heparin or glucosamine; but cholesterol sulfate, glucosamine sulfate, condroitin sulfate, and heparin sulfate.  Without sulfate, the body cannot produce or utilize these important biomolecules.  No sulfate means no heparin sulfate which leads to blood clots like heart attcks, stroke and pulmonary embolism. 

You might also have also heard of gutathione.  Glutathione (GSH) is the master antioxidant for each cell. Glutathione protects the cell from oxidative damage. When dietitians tell us to eat a diet of fresh fruits and veggies rich in antioxidants, those antioxidant keep glutathione in its protective state.  Glutathione is chock full of sulfur amino acids.  You could consume all the antioxidants possible, but without sulfate you wouldn't produce the glutathione for the other antioxidants to keep active.

Humans get sulfate in two ways.  First, we can directly consume inorganic sulfate.  The body easily absorbs sulfate and distributes it throughout the body.  Second, if there is not enough inorganic sulfate in the diet, the body can convert sulfur-containing amino acids in protein like methionine and cysteine into sulfate. In fact, despite the importants of sulfate to our health, the FDA makes absolutely no recommendations for our daily sulfate requirement. Sadly, the government considers sulfate to be a acid rain-causing pollutant and has gone to great lengths to scrub it out of our coal and gasoline.

The FDA assumes that we can just get all the sulfate we need by converting sulfur amino acids into sulfate. The problem with this is that converting methionine and cysteine to sulfate is very expensive and requires B12, B6, and folate to do the transformation.

What I'm saying is that that all these modern chronic inflammatory diseases may be helped by getting more inorganic sulfate in the diet.  How do you do this? Epsom salt is magnesium sulfate and easily found at every corner pharmacy and grocery store in the western world.  In addition, in contrast to the hundreds and even thousands of dollars of prescription medicine that many consume on a monthly basis to control but never cure these diseases, epsom salt is less than 1$.

We have romantic stories of the fountain of youth and healing in volcanic springs.  FDR even stayed at Warm Springs, GA recuperating from Polio. However, it just may be that it wasn't soaking in these sulfated waters that was healing but drinking them.

Now if you think that this theory about epsom salt and sulfate is too good to be true, consider 1. magnesium sulfate is already used very effectively to treat several acute exacerbations of chronic inflammatory conditions like asthma, migraine and preeclampsia. 2. epsom salt is already safely taken as a home remedy by numerous very healthy 85-year-olds in the southern US.  This population who regularly consume epsom salt have much less disease than do their children. 3. Methyltrexate is a powerful chemotherapy drug that blocks folate metabolism that is also used to treat many of these inflammatory diseases.  By looking at the biochemical pathway above showing folate and homocysteine, I hope you can see that taking extra sulfate is a much easier way to boost sulfate than by blocking folate-dependent DNA repair pathways.

Why does being folate-deficiency cause inflammation?  The body will do what it needs to do to survive.  When the body is cold it will shunt bood away from the limbs to the core to preserve core body heat resulting in frostbite and loss of limbs before loss of life.  The body is a Master at "stealing from Peter to pay Paul".  

When the body is sulfate deficent, it will become catabolic and start to cannibalize sulfate from various tissues.  My hunch is that while the body is cannibalizing sulfate, there is a risk of the body developing an exaggerated immune response against a particular tissue. There may be genetic factors that predispose someone to which tissue this might be or it might be random chance.  An autoimmune response to the skin is eczema or psoriasis. A reaction in the lungs might be asthma or maybe sarcoidosis.  Once your body has been autoimmune-sensitized to a particular tissue type, because of immune memory, you may likely carry the risk of future exacerbations.  However, understanding the possible mechanism of disease, it may be possible to make simple alterations in diet to prevent future exacerbations.

Sodium Benzoate is a ubiquitous food preservative found in soda pop, imitation maple syrup, BBQ sauce, soy sauce, salad dressings, and even store-bought humus.  Sodium benzoate is a D-aminoacid oxidase inhibitor and blocks the conversion of homocysyeine to sulfate.  This dangerous food preservative should be avoided.  Sodium Benzoate can also be found naturally to ground cinnamon.  Accordingly, it is important to avoid exposure to this spice.  Cinnamon is used by some as a natural remedy for many of the same disease processes that sulfate benefits.  But I think supplementing sulfate is a better strategy than blocking the sulfate pathway midstream, diverting and feeding sulfate down certain metabolic pathway branches while at the same time starving other pathways.

Tylenol is a common pain reliever and fever reducer.  Tylenol is cleared from the body by being sulfated in the liver befire being excreted by the kidney.  However, Tylenol causes a second hit to body sulfate levels. The liver converts acetaminophen to a toxic radical metabolite known as NAPQI which depletes liver glutathione.  The NAPQI-glutathione depletion is what results in liver failure and death in tylenol overdose.  Studies have shown that children exposed to tylenol have a 500% increased assiciation of asthma.  Now association does not prove causation but I personally limit my tylenol exposure and  prefer ibuprofen for minor pain and fever.  

In addition to a possible causal relationship between sulfate deficiency and inflammatory illness is a link between insulin resistant diabetes and dementia and sulfate deficiency. One of the common places the body goes to steal sulfate is skeletal muscle. Low sulfate means low cholesterol sulfate which results in a sparsity of lipid rafts in muscle cell walls.  Lack of lipid rafts in muscle cell walls results in low Glut4 receptor insertion which causes the insulin resistance. So far I have 3 individuals who are petsonal friends with poorly controlled type 2 diabetes who started taking epsom salt and their blood sugars went from the 200-300 range immediately to the 120-150 range.  This is anecdotal, but research needs to start somewhere.

Dementia and sulfate follows a different but related mechanism.  We know that persons with defective Apo4e enzymes have a genetic predisposition to developing Alzheimer's dementia. Apo4e is involved with transporting fat and cholesterol to and from the brain.  What happens in the brain is sulfate deficiency may cause the Endoplasmic Reticulum in the bain to become deficient in cholesteol sulfate and become too rigid or too floppy (conflicting data).  Beta-amyloid precursor protein is then cleaved out of the ER in the wrong spot and instead of being targeted for the lysosome to be degrated, the beta-amyloid precursor protein deposits in the brain to form the characteristic plaques. I believe the whole dementia disease process is not only caused by the B-amyloid buildup but by general dysfunction of the ER as a whole whose job is to fold, finish and activate proteins via post-translational modifications in the cell. This is why Alzheimers usually mainly affects more recent memory.  New connections are not being made because the enzymatic machinery isn't working.  Taking extra oral inorganic sulfate in the form of epsom salt may regulate cholesterol sulfate in the brain ER and improve memory and maybe even halt or reverse the disease process before a certain point.

I also think there is potential benefit to taurine and sulfate supplementiation in pre-term and low weight birth. Pre-mature infants have impared liver and taurine production and are likely also globally sulfate deficient. Taurine and sulfate supplementation has already been studied and shown some positive effects.     

In the metabolic pathway above, methionine is needed in the creation of SAM or S-adenasylmethionine. SAM is a key methyl donor critical in the formation of neurotransmitters dopamine, norepinephine, epinephrine and serotonin.  Could it be that the root cause behind the explosion of mental illness, depression and anxiety could also be traced back to sulfate deficiency?  Instead of taking SSRI's or other expensive medications that alter seretonin and norepinephrine, could these disorders be treated by avoiding sulfate-modulating preservatives and sulfate supplementation?

Cancer is a disease that requires the accumulation of multiple DNA mutations. The body has a very sophisticated DNA repair mechanism to prevent mutation. Homocysteine and Methionine are also key intermediates in the folate cycle. And Folate is a critical component of DNA repair.  I don't think that it is such a big leap to assume that sulfate deficiency could also adversely affect DNA repair and be a contributing factor to the development of some cancers.  So, in addition to mental illness, inflammatory disease, there may also be a link between sulfate deficiency and cancer. 

Gestational hypertension, diabetes, preclampsia and ecclampsia are all associated with elevated homocysyeine levels.  Infact there exists a direct correlation with homocysyeine level and the severity of disease. When a women is pregnant, the developing fetus will steal the nutrients it needs from the mother.  I think all these severe gestational diseases are directly a result of sulfate deficiency.  Gestational hypertension is treated with methyldopa which is known to modulate the SAM pathway. Preeclampsia and eclampsia are already treated aggressively with IV mag sulfate.  All this time doctors assumed it was the Mg alone relaxing smooth muscle.  Maybe it is also the sulfate treating the root cause of the disease.

My recommendation for any adult with inflammatory illnesses, type 2 diabetes, dementia or a strong family history of these issues is to:

1. Avoid Sodium Benzoate preservative
2. Avoid Cinnamon (natural source of Sodium Benzoate).
3. Limit Tylenol exposure
4. Eat Healthy preservative-free diet
5. Exercise and get at least 20 min sun daily
6.  Take 1/4 tsp Epsom Salt Heptahydrate crystals in 8 oz liquid daily or once- or twice-a-day.

For severe debilitating illness like multiple sclerosis, scleroderma, rheumatoid arthritis, inflammatory bowel disease, etc:
6. Take 5000 Units D3 Daily
7. Take B12, B6, Folate vitamin daily 

Magnesium Sulfate is not necessarily a cure all. Once you have developed an autoimmune reaction against a particular tissue, your immune system has a long memory, and you will carry the risk of future exacerbations the rest of your life.  But the goal of sulfate supplementation is to manage future exacerbation. Once a person has developed hypertension, kidney failure or some other chronic disease, sulfate supplementation alone won't get rid of the scar tissue in the liver and lungs and it won't restore lost neurons and nephrons in the kidney.  But what it may do is prevent further injury, loss of reserves, and organ failure.

I do not generally believe that a healthy person without chronic disease and who maintains a healthy diet needs to necessarily supplement with Epsom Salt. I do think it is critical to minimize our exposure to sulfate depleting substances like acetaminophen and sodium benzoate including cinnamon.  But a person suffers from one or more chronic inflammatory diseases, if there is a strong family history of chronic disease, or if a person desires the pro-biotic affects of Epsom salt, supplementation will likely be beneficial.