Vitamin D: Not a simple case of cause and effect

I swear I didn't plan to grow up and become a vitamin D cowboy, but here I am, again galloping into the vitamin corral, again trying to get an intellectual rope around the question of whether the "sunshine vitamin" really is medicine's next clap-hands-hosanna — or not.

The context for this reflection are four presentations about what has come to be known as the Marshall Protocol made in September in Portugal at the 6th International Congress on Autoimmunity. In a 21st-century world in which the talk everywhere seems to be that taking much, much more vitamin D — five to 10 times the present recommended dosage — is needed if humans in northern and far southern countries are to curtail cancers and slack the growth of autoimmune diseases, the Marshall presenters reached a 180-degree, U-turn of a conclusion.

Looking at more than 1,000 people with a host of autoimmune and related diseases, the researchers said that — when combined with a particular drug treatment program — people who consciously tried not to take vitamin D and stayed out of the sun showed an often-dramatic reduction in symptoms. Dramatic means a reduction of 81 per cent in symptoms for people suffering from conditions ranging from Type 2 diabetes, to rheumatoid arthritis, to multiple sclerosis, Lyme disease and Crohn's disease.

One drug in the protocol is called olmesartan, a medication currently approved for high blood pressure and vitamin-D-reduction use in certain diseases, and the others are low doses of certain antibiotics.

What is the rationale for this treatment? A very, very complicated body biology.

Marshall Protocol initiator Trevor Marshall later told me that it is scientifically accepted that forms of vitamin D act as a steroid that, among other things, modulates the body's immune responses. In his model, certain kinds of bacteria invade the white cells that the body uses to fight and destroy foreign invaders. The compromised cells respond by generating inflammation. The inflammation ends up throwing off the body's ability to effectively use vitamin D to ramp up and dampen down immune responses. The form of vitamin D that is usually measured to determine deficiency has to be converted to another active form and, without that conversion, according to Marshall, the vitamin D supplements actually dampen down the immune system.

This immune suppression allows the bacteria inside the white cells to multiply. As they do, the inflammation that Marshall sees lying at the root of autoimmune diseases increases and with that, another round of inflammation is generated.

In the protocol, the banning of vitamin D prevents the imbalance from self-perpetuating; the olmesartan returns the immune system response to its normal state, so that the antibiotics can kill the rogue bacteria.

What does this mean for the more-vitamin-D-is-good-for-you debate?

In a paper entitled Vitamin D discovery outpaces FDA decision-making, which Marshall published last year in the peer reviewed journal BioEssays, he wrote the following immensely provocative few sentences: "For half a century, medical science has been noting the association between vitamin D serum levels and disease. What developed has been a concept of 'vitamin D deficiency' based solely on the notion that 'low' vitamin D serum levels somehow cause disease processes. But this ignores the alternative hypothesis — that the disease processes themselves regulate the vitamin D metabolism  —that the observed 'low' values of vitamin D in disease are a result of the disease process, not the cause."

Oof. The supposed cause is the really an effect. Oof.

I report this to you and then almost as quickly want to rein back on what I have told you. The Marshall Protocol is not your classic double-blind/don't tell patients who is getting antibiotics and olmesartan and who isn't sort of thing. Everyone who enrolls, with their doctor's approval, gets the drugs. There is no part of the study in which people are encouraged to go into the sun or take more vitamin D. The people who went into the study were all very sick, "at the end of their ropes," Marshall says, and were looking for something, anything, to make their pain-filled lives better.

Moreover, the presenters generally had rather unconventional backgrounds. Marshall is a PhD electrical engineer who has gotten heavily involved with computer simulations of various sorts, and his PhD thesis was entitled Modelling and Simulation in Diabetes Care. Another was a retired captain in the Commission Corps of the U.S. Public Health Services who worked in the Food and Drug Administration. And yet another had a BA in biology and wrote her senior thesis on the Marshall Protocol.

Most seem to have one or another of the conditions which the treatment is designed to cure.

That is to say they are, as they say in French, parti pris. They really want the treatment to work because they really need it to work in their lives. This means that the fabled placebo effect, with its oft times 30 per cent improvement level, may be part of what is going on.

As well, Marshall doesn't plan to have the protocol's results submitted to a peer-reviewed journal for publication. He is just going to speak at meetings. Why? He complains about the medical community's inability to appreciate the new biochemistry of the genes and its subsequent unwillingness to move beyond the double-blind study.

"Our studies were designed to make breakthroughs, not to fit into paradigms that big medicine was capable of understanding," he tells me. "I think it is highly unlikely we will be publishing our study results. I think others will replicate our work and they will publish."

Or not. Maybe what others' published research will show is that Marshall is wrong — something peer review would let him see today.

And it is also fair to say that much of the conventional scientific community thinks Marshall's science — what he personally does is generate computer simulations of how cells and proteins might interact — is somewhere between plain wrong and awfully loony. "His paper really ignored large swatches of literature on vitamin D functions. There is nothing in what he has said or published that modifies my views about how vitamin D works," is how John White, a molecular geneticist at McGill University who late last year published an extensive piece in Scientific American about vitamin D and its effect on cells, views Marshall's research.

What is particularly lacking is "wet" data — that is, actual experiments with cells and vitamin D that show that Marshall's computer-based theories are correct.

Quite damning in this regard, White will soon submit for publication an experiment which contradicts some of Marshall's computer-based theories of how the body processes vitamin D.

Now my intellectual horse rears up another time. However flawed it may turn out to be, at least the Marshall Protocol presents a clear biochemical pathway that explains what happens in diseases and how vitamin D effects the body.

This is in clear contrast to those who advocate taking much greater amounts of vitamin D. They haven't clearly defined the mechanisms by which the vitamin can cure you or prevent a disease from occurring. And there is a reason for this. The more we know about vitamin D, the more complicated its actions in the body seem. White reported in his Scientific American paper that at least 1,000 genes are regulated by 1,25 D, the metabolically active form of the vitamin.

Even this is likely a low estimate of its ultimate effect. White writes in the same paper that many other genes are influenced by vitamin D activity.

What this suggests is that whatever happens with vitamin D and disease, the process is likely extremely complicated. And thus increasing dosage is something one wants to do with great, great care. This is not a world of a cause and an effect; this is a body planet where a multiplicity of disease causes and a multiplicity of medicine effects are occurring.

With this in mind, White, who publicly admits that he now takes 4,000 international units of the vitamin daily in winter instead of Health Canada's presently recommended 200, also preaches caution.

"I am very concerned people are going to have the expectation that vitamin D will cure everything — and it will not," he tells me with high seriousness. "You have to keep a certain distance and be critical here, and I would argue that some vitamin D proponents are just as guilty [as Marshall], but in the other direction. Taking vitamin D doesn't mean that all of a sudden no one is never ever going to get cancer, no one is ever going to get multiple sclerosis anymore, etc, etc."

And with that, my intellectual horse, much like Stephen Leacock's, rears up a final time and — in its still uncertain search for the truth about vitamin D and disease — gallops off in all directions.