Sunday, July 20, 2014

Sulfate and Chronic Disease

Inorganic Sulfate is one of the most abundant anions in human and mammalian plasma. Sulfate plays an important physiological role in detoxifying xenobiotics, activating steroids, cholesterol, vitamin D, neurotransmitters, and bile acids. Sulfate is needed for the biosynthesis of glycosaminoglycans, cerebroside sulfate, and heparin sulfate.  Sulfate conjugation is a major liver pathway necessary for detoxifying and excreting toxins in the body and bloodsteam.  In mammals, sulfate homeostasis is regulated by the kidney. The majority of filtered sulfate is reabsorbed in the proximal tubules, and only 5–20% of the filtrate is excreted into the urine.

A few recent scientific papers are making a possible connection between serum sulfate levels and several chronic diseases including: osteoarthritis, preeclampsia, dementia, inflammatory bowel disease, peptic ulcer disease, hypertension, type 2 diabetes, DIC, asthma, eczema, lupus, chronic fatigue, wrestless legs, multiple sclerosis, autism, heart disease and cancer. How could all these different conditions be related? Well, the thinking is that all these chronic diseases are related to serum sulfate deficiency, and the specific disease process depends on where in the body sulfate is being scavenged/cannabilized from. 

Interesting point here is that sulfate-containing medicines are already used in many of these disease processes. Magnesium sulfate is already used in preeclampsia, hypertension, and asthma. Vitamin D has been shown to improve symptoms in autism, multiple sclerosis, dementia, inflammatory bowel and numerous other autoimmune conditions. Chondroiton sulfate is used in osteoarthritis, and heparin sulfate is used in DIC.

What is the connection between vitamin D and sulfate?  Turns out sun exposure not only activates vitamin-D but also is required to produce cholesterol sulfate and vitamin-D sulfate. Cholesterol sulfate is then incorporated into cell walls and endoplasmic reticulum to increase cell wall plasticity, protect from oxidative damage, facilitate transmembrane glucose transport, and protein post-translation modifications. 

Tragically, despite its importance, sulfate metabolism is not discussed much if at all in modern medical education.  Also, serum and urinary sulfate levels are not routinely measured in the hospital or clinical settings. In fact in all my medical career, I have never seen or heard of a serum or urinary sulfate level being checked.  Sulfate concentration is easily measured using a barium assay.

Furthermore. there are several factors that can lead to deficiencies in sulfate levels.  1. Penicillin antibiotics kill nitrate-metabolizing bacteria in the gut but not sulfate-metabolizing bacteria. Sulfate-metabolizing bacteria overgrow and reduce whole-body sulfate levels. 2. Aluminum (Alum) containing adjuvant vaccines can lead to deficiencies in serum sulfate, vitamin D sulfate, and cholesterol sulfate.  3. Consumption of Alum-containing foods such as pickles, iodized salt, and baking powder can exacerbate these disease states.  4. Fasting followed by the consumption of a carbohydrate-only meal can lead to a significant 50% drop in serum sulfate levels. 5. Statins inhibit cholesterol syntheses in the liver and brain. 6. Oil-in-water squalene vaccines can result in anti-cholesterol and anti-vitamin D antibodies.  7. The increased clearance of vitamin D and cholesterol by the immune system because of either Alum or squalene adjuvants can lead to decreased total body serum sulfate levels. 8. Tylenol (acetaminophen) ingestion causes decreased sulfate levels due to liver detoxification via sulfate conjugation (phase 2) and consumption of the sulfur-containing glutathione antioxidant.

The key to treating many of these disease states may be simply to supplement the diet with magnesium sulfate or Epsom salt and vitamin D3.  Epsom salt is safe to consume orally except in those with kidney failure. Ingesting too much MgSO4 will be eliminated by the kidney or not absorbed at all, resulting in diarrhea. Like sodium, potassium, and calcium, it is important not to take more magnesium than the body needs and can excrete.  Despite what advertisements claim, sulfate is not absorbed in any significant way by adding MgSO4 to the bath water. The only benefit of an Epsom salt bath is that you can stay in longer without getting pruney.

A safe daily dose of Epsom salt is about 1/2 tsp MgSO4 in 8 oz. fluid.  This works out to be about 2.5 gm MgSO4.7H2O or 250 mg elemental magnesium (10%).  In addition to supplemental sulfate, 5000-10,000 units of vitamin D daily is also recommended.  For comparison, 10 minutes of sun expose produces 10,000 units of Vitamin D. However, in addition to vitamin D supplementation, getting at least 10 minutes of sun exposure daily is necessary to produce cholesterol sulfate.  

*****1 tsp MgSO4.7H2O (magnesium sulfate heptahydrate) = approx. 5 gm/tsp = 10% elemental Mg = 500 mg per tsp.
*****RDA of Magnesium is about 400 mg daily.

As far as cholesterol itself goes, the liver already makes 1-2 gm daily which is much more cholesterol than you could ever ingest by eating eggs (300-500 mg).  However, eating eggs is still important because the lecithin in egg yoke is required for efficient transport of cholesterol out of the liver. 

You might wonder why you can't just get enough sulfate in your diet without supplementing. The answer is because most food is grown using inorganic fertillizer which, except for Austrailia, does not include sulfur.  Even organically grown food can be sulfur deficient because the chickens and cattle that produce the manure are fed a sulfate poor feed (soy and corn) and consequently produce a sulfate-poor manure.

I believe God did not create the human body to have the myriad of chronic health problems we are now seeing. Even among those who try and eat healthy and exercise regularly are seeing an explosion of chronic disease. The way I see it, either God designed a flawed human body or we are ingesting something harmful (nitrites) and/or missing something essential in our diets (sulfates).

According to the Institute of Medicine, Food and Nutrition Board 2004 "Dietary Reference Intakes: Water, Potassium, Sodium, Chloride, and Sulfate", they give no recommended daily intake of sulfate. They list a long but still incomplete table of sulfate-containing biochemicals in the body.  However, their conclusion is that recycled sulfate from protein and dietary protein is probably enough. They also say sulfate is an industrial pollutant, tastes bad in well water, and could give you diarrhea. Also, they say supplemental sulfate could lead to ulcerative colitis. This assertion is based on a study finding of sulfur-metabolizing bacteria in the gut of patients with UC. (this dismissive attitude against sulfate makes me a little suspicious)

But as I point out above, the sulfur-metabolizing bacteria actually lower overall sulfate levels which is more likely the cause of UC and not the presence of the bacteria and the resultant hydrogen sulfide gas itself. For one thing, treatments targeting the bacteria do not cure the disease.  Correlation does not equal causation.

My argument in advocating for sulfate supplementation is precisely for the reason stated in the Institute of Medicine guidelines paper.  They say you don't need sulfate because you can simply cannabilize it from protein and other molecules.  This cannabilization I believe is precisely the cause of many of the chronic diseases we are seeing today.

FYI: I do not generally advocate vitamin or mineral supplementing.  I think in most cases, taking excess vitamins and minerals can cause more harm than good and studies have not shown benefit but increased harm (manganese, vitamin E, etc).

In mice lacking the vitamin D receptor (VDR), NaSi-1 expression in the kidney was reduced by 72% but intestinal NaSi-1 levels remained unchanged. In connection with these findings, urinary sulfate excretion was increased by 42% whereas serum sulfate concentration was reduced by 50% in VDR knockout mice. Moreover, levels of hepatic glutathione and skeletal sulfated proteoglycans were also reduced by 18 and 45%, respectively. (Yan et al., Critical role of vitamin D in sulfate homeostasis, 2004)

According to the national guidelines, the body metabolizes up to about 3 - 6 gm inorganic-source and organic-source sulfate daily. According to the article, at least 1.5 - 3 gm comes from inorganic-source sulfate in food and water and 1.5 -3 gm organic-source sulphate comes from digestion and breakdown of sulfur-amino-acids. However, they make a point that total dietary sulfate can be much less than 1.5 gm.  Soy and corn are poor quality protein sources precisely because of their low sulfur-amino-acid content.

MgSO4.7H2O -- Mg: 24, SO4: 32 + 16 x 4 = 98, 7H2O: 16 + 2 = 18 x 7 = 126
Total mass per mole = 248
% Mg = 24/248 = 10%
% SO4 = 98/248 = 40%

Interesting that 1/2 the mass of MgSO4 is water and there can be variation in how much 1 tsp weighs depending on humidity and storage from 4.5 gm/tsp to 6.5 gm/tsp.   But anyways, assuming about 1 tsp = 5 gm, then SO4 would be about 2 gm SO4. 1/4 tsp would be 500 mg SO4.

A study of Vets measuring serum sodium measured got a range of 0.2 mM to 0.5 mM.  It would be really super hard to predict an increase in serum levels by 500mg or 2 gm oral Sulfate because of considering absorption (80%), and elimination and whole body distribution. Like other electrolytes like Mg and K etc, the serum levels are only a tiny fraction of the whole body stores.  But I think that it is good when you are thinking about taking a supplement that you are within the ballpark. (considering normal kidney function).

Im curious if pernicious anemia (B12 deficiency) could be another manifestation of sulfate deficiency. If the body is sulfate deficient then it starts to scavenge it from various places in the body. When you don't get enough dietary sulfate the body will begin to cannibalize parts of the body to get it. Homocysteine is an inflammatory breakdown product of protein that then must be converted to sulfate via folate, thiamine, B12 etc. Elevated homocysteine can be a sensitive marker for B12 deficiency. Unless a patient has a deficiency in intrinsic factor, more B12 may not be the only answer. It may be that an elevated homocysteine level and low B12 indicates a catabolic state.

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