Vitamin D3-sulfate

[Kasper]

I found this an interesting article from the weston price foundation about vitamin D and sulfur. It is very long, but here are the parts about vitamin D3:

"Upon exposure to the sun, the skin synthesizes vitamin D3 sulfate, a form of vitamin D that, unlike unsulfated vitamin D3, is water soluble. As a consequence, it can travel freely in the blood stream rather than encapsulated inside LDL (the so-called “bad” cholesterol) for transport.1 The form of vitamin D that is present in both human milk19 and raw cow’s milk2 is vitamin D3 sulfate (pasteurization destroys it in cow’s milk).
Cholesterol sulfate is also synthesized in the skin, where it forms a crucial part of the barrier that keeps out harmful bacteria and other microorganisms such as fungi.35 Cholesterol sulfate regulates the gene for a protein called profilaggrin, by interacting like a hormone with the nuclear receptor ROR-alpha. Profilaggrin is the precursor to filaggrin, which protects the skin from invasive organisms.31,24 A deficiency in filaggrin is associated with asthma and arthritis. Therefore, cholesterol sulfate plays an important role in protection from asthma and arthritis. This explains why sulfur is a healing agent.
Like vitamin D3 sulfate, cholesterol sulfate is also water-soluble, and it too, unlike cholesterol, does not have to be packaged up inside LDL for delivery to the tissues.
Here I pose the interesting question: where do vitamin D3 sulfate and cholesterol sulfate go once they are in the blood stream, and what role do they play in the cells? Surprisingly, as far as I can tell, nobody knows. It has been determined that the sulfated form of vitamin D3 is strikingly ineffective for calcium transport, the well-known “primary” role of vitamin D3.29 However, vitamin D3 clearly has many other positive effects (it seems that more and more are being discovered every day), and these include a role in cancer protection, increased immunity against infectious disease, and protection against heart disease. Researchers don’t yet understand how it achieves these benefits, which have been observed empirically but remain unexplained physiologically. However, I strongly suspect it is the sulfated form of the vitamin that instantiates these benefits, and my reasons for this belief will become clearer in a moment.
One very special feature of cholesterol sulfate, as opposed to cholesterol itself, is that it is very agile: due to its polarity it can pass freely through cell membranes, almost like a ghost.30 This means that cholesterol sulfate can easily enter a fat or muscle cell. I am developing a theory which at its core proposes an essential role for cholesterol sulfate in the metabolism of glucose for fuel by these cells. Below, I will show how cholesterol sulfate may be able to protect fat and muscle cells from damage due to exposure to glucose, a dangerous reducing agent, and to oxygen, a dangerous oxidizing agent. I will further argue that, with insufficient cholesterol sulfate, muscle and fat cells become damaged, and as a consequence become glucose intolerant, unable to process glucose as a fuel. This happens first to muscle cells but eventually to fat cells, as well. Fat cells become storage bins for fats to supply fuel to the muscles, because the muscles are unable to utilize glucose as fuel. Eventually, fat cells also become too disabled to release their stored fats. Fatty tissue then accumulates on the body.

....

IS THE SKIN A SOLAR-POWERED BATTERY FOR THE HEART?
The evidence is quite compelling that sunny places afford protection from heart disease. A study described in a 1996 issue of QJ Med.14 provides an in-depth anaylsis of data from around the world showing an inverse relationship between heart disease rates and a sunny climate and a low latitude. For instance, the cardiovascular-related death rate for men between the ages of 55 and 64 was 761 per 100,000 men in Belfast, Northern Ireland, but only 175 in Toulouse, France. While the obvious biological factor that would be affected by sunlight is vitamin D, studies conducted specifically on vitamin D status have been inconclusive, with some even showing a significant increased risk for heart disease with increased intake of vitamin D2 supplements12.
I believe, first of all, that the distinction between vitamin D3 and vitamin D3 sulfate really matters, and also that the distinction between vitamin D2 and vitamin D3 really matters. Vitamin D2 is the plant form of the vitamin. It works similarly to D3 with respect to calcium transport, but it cannot be sulfated. Furthermore, apparently the body is unable to produce vitamin D3 sulfate directly from unsulfated vitamin D3 19 (which implies that it produces vitamin D3 sulfate directly from cholesterol sulfate). I am not aware of any other food source besides raw milk that contains vitamin D3 in the sulfated form. So, when studies monitor either vitamin D supplements or vitamin D serum levels, they’re not getting at the crucial aspect for heart protection, which I think is the serum level of vitamin D3 sulfate.
Furthermore, I believe it is extremely likely that vitamin D3 sulfate is not the only thing that’s affected by greater sun exposure, and maybe not even the most important thing. Given that cholesterol sulfate and vitamin D3 sulfate are very similar in molecular structure, I would imagine that both molecules are produced the same way. And since vitamin D3sulfate synthesis requires sun exposure, I suspect that cholesterol sulfate synthesis may also exploit the sun’s radiation energy.
Both cholesterol and sulfur afford protection in the skin from radiation damage to the cell’s DNA, the kind of damage that can lead to skin cancer. Cholesterol and sulfur become oxidized upon exposure to the high frequency rays in sunlight, thus acting as antioxidants to “take the heat,” so to speak. Oxidation of cholesterol is the first step in the process by which cholesterol transforms itself into vitamin D3. Sulfur dioxide in the air is converted nonenzymatically to the sulfate ion upon sun exposure. This is the process that produces acid rain. The oxidation of sulfide (S-2) to sulfate (SO4 -2), a strongly endothermic reaction15, converts the sun’s energy into chemical energy contained in the sulfur-oxygen bonds, while simultaneously picking up four oxygen molecules. Attaching the sulfate ion to cholesterol or vitamin D3is an ingenious step, because it makes these molecules water-soluble and therefore easily transportable through the blood stream.
Hydrogen sulfide (H2S) is consistently found in the blood stream in small amounts. As a gas, it can diffuse into the air from capillaries close to the skin’s surface. So it is conceivable that we rely on bacteria in the skin to convert sulfide to sulfate. It would not be the first time that humans have struck up a symbiotic relationship with bacteria. If this is true, then washing the skin with antibiotic soap is a bad idea. Phototrophic bacteria, such as Chlorobium tepidum, that can convert H2S to H2SO4 exist in nature39,36, for example in sulfur hot springs in Yellowstone Park. These highly specialized bacteria can convert the light energy from the sun into chemical energy in the sulfate ion.
Another possibility is that we have specialized cells in the skin, possibly the keratinocytes, that are able to exploit sunlight to convert sulfide to sulfate, using a similar phototrophic mechanism to C. tepidum. This seems quite plausible, especially considering that both human keratinocytes and C. tepidum can synthesize an interesting UV-B absorbing cofactor, tetrahydrobioptin. This cofactor is found universally in mammalian cells, and one of its roles is to regulate the synthesis of melanin,34 the skin pigment that is associated with a tan and protects the skin from damage by UV-light exposure.9 However, tetrahydrobiopsin is very rare in the bacterial kingdom, and C. tepidum is one of the very few bacteria that can synthesize it.37
Let me summarize at this point where I’m on solid ground and where I’m speculating. It is undisputed that the skin synthesizes cholesterol sulfate in large amounts, and it has been suggested that the skin is the major supplier of cholesterol sulfate to the blood stream.35 The skin also synthesizes vitamin D3 sulfate upon exposure to sunlight. Vitamin D3 is synthesized from cholesterol, with oxysterols (created from sun exposure) as an intermediate step (oxysterols are forms of cholesterol with hydroxyl groups attached at various places in the carbon chain). The body can’t synthesize vitamin D3 sulfate from vitamin D3 19 so it must be that sulfation happens first, producing cholesterol sulfate or hydroxy-cholesterol sulfate, which is then optionally converted to vitamin D3sulfate or shipped out “as is.”
Another highly significant feature of skin cells is that the skin stores sulfate ions attached to molecules that are universally present in the intracellular matrix, such as heparan sulfate, chondroitin sulfate, and keratin sulfate26. Furthermore, it has been shown that exposure of the melanin-producing cells (melanocytes) to molecules containing reduced sulfur (-2) leads to suppression of melanin synthesis,7 whereas exposure to molecules like chondroitin sulfate that contain oxidized sulfur (+6) leads to enhancement of melanin synthesis.18Melanin is a potent UV-light absorber, and it would compete with reduced sulfur for the opportunity to become oxidized. It is therefore logical that, when sulfur is reduced, melanin synthesis should be suppressed, so that sulfur can absorb the solar energy and convert it to very useful chemical bonds in the sulfate ion.
The sulfate would eventually be converted back to sulfide by a muscle cell in the heart or a skeletal muscle (simultaneously recovering the energy to fuel the cell and unlocking the oxygen to support aerobic metabolism of glucose), and the cycle would continually repeat.
Why am I spending so much time talking about all of this? Well, if I’m right, then the skin can be viewed as a solar-powered battery for the heart, and that is a remarkable concept. The energy in sunlight is converted into chemical energy in the oxygen-sulfur bonds, and then transported through the blood vessels to the heart and skeletal muscles. The cholesterol sulfate and vitamin D3-sufate are carriers that deliver the energy (and the oxygen) “door-to-door” to the individual heart and skeletal muscle cells.
Today’s lifestyle, especially in America, severely stresses this system. First of all, most Americans believe that any food containing cholesterol is unhealthy, so the diet is extremely low in cholesterol. Eggs are an excellent source of sulfur, but because of their high cholesterol content we have been advised to eat them sparingly. Second, as I discussed previously, natural food plant sources of sulfur are likely to be deficient due to sulfur depletion in the soil. Third, water softeners remove sulfur from our water supply, which would otherwise be a good source. Fourth, we have been discouraged from eating too much red meat, an excellent source of sulfur-containing amino acids. Finally, we have been instructed by doctors and other authoritarian sources to stay out of the sun and wear high SPF sunscreen whenever we do get sun exposure.
Another significant contributor is the high carbohydrate, lowfat diet, which leads to excess glucose in the blood stream, which glycates LDL particles and renders them ineffective in delivering cholesterol to the tissues. One of those tissues is the skin, so skin becomes further depleted in cholesterol due to glycation damage to LDL."

[dime]

It's a lot of guessing and assumptions in that article.. as usual people looking for the holly grail of health.
There's very scarce research on vitamin D sulfate. This says it's a much less potent alternative of vitamin D.
I can't access this, seems more recent: http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract

So we don't know what's the exact role of vit. D sulfate, but we know it can only made from sunlight exposure. So IF vit. D sulfate is important, then supplements don't completely help you.

[overkees]

In the article you can't get acces to they refer to the following articles:

[overkees]

Alot of experiments quoted are japanese experiments from the 60ies. The article says that there are alot of problems with the methods.

See this one for example:
When administered as a single intravenous dose, vitamin D3 sulfate exhibited no biological activity in doses as high as 52,000 pmol. Vitamin D3, however, was active at a dose of as low as 65 pmol. We conclude that vitamin D3 sulfate, a metabolite of vitamin D3 of heretofore unknown biological activity, is considerably less active than vitamin d3 itself.
http://www.ncbi.nlm.nih.gov/pubmed/6256368

These results disprove previous claims that vitamin D3-sulfate has potent biological activity, and they further do not support the contention that vitamin D-sulfate represents a potent water-soluble form of vitamin D in milk.
http://www.ncbi.nlm.nih.gov/pubmed/6256368

Although added cholecalciferol sulfate was readily detected in human milk whey samples, no endogenous vitamin D sulfate was found (detection limit 1 ng/ml). The results indicate that vitamin D sulfate is not a major source of vitamin D activity in human milk.
http://www.ncbi.nlm.nih.gov/pubmed/6257870

[overkees]

Here is a very good full article that you can have acces to that also discusses the japanese results:

http://www.ncbi.nlm.nih.gov/pmc/article ... 2-0088.pdf