Science behind vitamin D

All forms of vitamin D are secosteroids, sharing a close structural and functional resemblance to steroids. The full implications of a “vitamin” acting as a steroid has yet to be fully appreciated by many in the research community. The overlap between steroids and secosteroids is key to understanding the Marshall Pathogenesis. It explains how a “vitamin” can exert short-term palliative effects and long-term harm. Patients on the MP are advised to avoid consuming vitamin D, because of its immunomodulatory effects.

A number of studies have suggested that patients with chronic inflammatory diseases are deficient in 25-hydroxyvitamin-DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver. (25-D) and that consuming greater quantities of vitamin D, which further elevates 25-D levels, alleviates symptoms of disease. Some years ago, molecular biology identified 25-D as a secosteroid. Secosteroids would typically be expected to depress inflammation, which is in line with the reports of symptomatic improvement. The simplistic first-order mass-action model used to guide the early vitamin studies has given way to a more complex description of action. When active, the Vitamin D nuclear receptor (VDR) affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides.

Located in the nucleus of a variety of cells including immune cells, the VDR is a control system of sorts. When exposed to infection and damage, especially that which is caused by pathogens, the body begins to convert the inactive form 25-D into the active form, 1,25-D. As cellular concentrations of 1,25-D increase, 1,25-D activates the VDR, turning on any number of tens of thousands of genes the receptor transcribes. The activation of certain genes leads to the synthesis of antimicrobial peptides. The antimicrobial peptides are the body's “natural antibiotics” and have a potent anti-bacterial effect.

However, bacteria create ligands, which like 25-D, inactivate the VDR and, in turn, the innate immune responseThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease.. This allows the microbes to proliferate. In response, the body increases production of 1,25-D from 25-D, leading to one of the hallmarks of chronic inflammatory disease: a low 25-D and a high 1,25-D.

This pattern is a result of the disease process rather than a cause. For a variety of reasons, neither increased consumption of vitamin D nor the body's synthesis of additional 1,25-D is ultimately effective at combatting infection.

Both osteoporosis and osteopenia are diseases marked by a decrease in bone mineral density. Osteopenia is a less severe form of and sometimes precursor to osteoporosis. The loss of bone mass leads to a porous bone structure, frequent fractures, and delayed healing.

Among doctors, and even many researchers, it is conventional wisdom that vitamin D supplementation reverses osteopenia and osteoporosis. However, a growing body of interventional trials and molecular evidence shows this is not the case. Instead, current research has demonstrated that osteoporosis and osteopenia are often the direct result of infection with the Th1 pathogens, a metagenomic microbiotaThe community of bacterial pathogens including those in an intracellular and biofilm state which cause chronic disease., which produce inflammatory cytokines and inactivate the Vitamin D Receptor. The only way to achieve long-term reversal of bone loss is to kill the Th1 pathogens driving the disease process.

Rickets (osteomalacia) is a softening of the bones that leads to fractures and deformity. The majority of cases of rickets occur among children in developing countries who suffer from severe malnutrition. The disease is cited as a primary reason for consuming vitamin D regularly even though research has demonstrated that rickets is not caused by vitamin D deficiency but by hypophosphatemia.

The latest molecular evidence does not support adding high levels of vitamin D to the food chain in the name of “preventing rickets.” The health of the public would be much better served by regulations ensuring that they obtain adequate calcium and phosphorous rather than vitamin D.

A variety of studies have suggested that vitamin D protects against cancer. This seemingly intuitive proposition is supported by neither epidemiological nor molecular evidence. In fact, the very opposite is true. This article reviews why this body of research is most likely incorrect – or at the very least, much more complicated than articles in the popular media would have a person believe.

• Latitude studies - The “latitude studies” are observational, as opposed to interventional, studies, which use ambient solar UV radiation as a proxy for latitude and vitamin D status. For these studies, researchers compare rates of certain major cancers - most notably breast, colorectal and prostate cancer - to rates of sunlight exposure. This group of research has the liability of being wildly inconsistent. The choice to publish research on a specific latitude gradient may be a better proxy for a researcher's bias.
• Interventional studies - While some randomized controlled trials have suggested that consuming vitamin D reduces rates of cancer, larger and more carefully controlled studies show no such effect.
• Studies of vitamin D status - Many of the studies examining the relationship between vitamin D status and incidence of cancer argue that low levels of 25-D contribute to cancer. This conclusion has been invalidated by larger well-controlled studies. Although the immune system works to downregulate 25-D (25-hydroxyvitamin D) in inflammatory diseases such as cancer, very high levels of 25-D are a clear indication of regular supplementation. These studies suggest that consuming large amounts of vitamin D predispose a person to increased incidence of cancer.
• Observational studies – Some case control studies have found that vitamin D intake seems to increase incidence of certain types of cancer.

According to the Marshall Pathogenesis, light-related changes in mood can be attributed to fluctuations in 1,25-dihydroxyvitamin D (1,25-D). Such reactions exist in people who suffer from “seasonal affective disorder” as well as those who are addicted to or dependent upon tanning.

Contrary to popular belief, epidemiological research points to an increase in suicide across countries during the beginning of the summer months when people tend to get more light exposure.

Light exposure does nothing to resolve underlying disease state and can actually delay progress for Marshall Protocol (MP) patients. Certainly prolonged light exposure has been shown to increase skin melanoma – the World Health Organization now categorizes tanning beds under the highest cancer risk category.²

MP patients who have completed the treatment have been able to attest to the fact that sunshine is not necessary for good health or happiness.

Despite what some researchers have argued, latitude studies that try to tie ambient solar UV radiation to prevalence of disease have been inconclusive.

1,25-D rises by 40% in the early pregnant decidua, meaning that its ability to dysregulate the nuclear receptors and the antimicrobial peptides (AmPs) they express is particularly prevalent during the first trimesters of pregnancy. The subsequent decrease in immune function slows immunopathology, resulting in symptomatic relief. But when the surge in 1,25-D disappears after pregnancy, AmP expression and immunopathology increase once again, leading to exacerbation of disease symptoms. This may explain why some women with autoimmune disease experience periods of palliation during gestation only to become increasingly symptomatic after giving birth.

One of the abiding weaknesses of studies on the effects of vitamin D on health is that researchers simply do not follow subjects consuming the secosteroid for a sufficient period of time. Instead, they tend to track subjects over the course of weeks, months, or one or two years, during the period of time when study participants are usually feeling the palliative effects of the steroid. This practice is a mistake as it does not account for the long-term immunosuppressive effects of a steroid.

It is arguably impossible to sufficiently control for the socioeconomic factors, which drive a person to participate in a therapy or take a supplement. The case of hormone replacement therapy (HRT) is instructive. For decades, researchers thought that HRT prevented disease, but it was ultimately shown that it caused it.

Studies of vitamin D's efficacy are especially fraught with challenges. For one, the secosteroid is palliative and the negative side effects can only be seen after decades of use. Also, people who take vitamin D are demonstrably different than those who don't. They almost always have a higher socioeconomic status.

Not all studies on vitamin D's efficacy are observational, but those that are may warrant a special amount of skepticism.

Many vitamin D studies suffer from methodological errors including bias inherent to using self-selected subjects and insufficient followup, but perhaps their most egregious liability comes in mistaking correlation for causation.

It's undisputed that a wide array of studies point to the fact that 25-hydroxyvitamin D (25-D) – typically referred to in the media as vitamin D – is low in people with numerous chronic inflammatory diseases. However, these studies fail to prove that low 25-D causes disease.

In fact, molecular science has revealed that the levels of the vitamin D metabolites through a series of intricate and carefully controlled feedback pathways, mechanisms that belie the simplistic first-order mass-action model used to guide the short-sighted vitamin studies. Also, epidemiological evidence suggests that while 25-D is low in chronic disease, 1,25-D (1,25-dihydroxyvitamin D) tends to be very high, an observation which is at odds with the theory that vitamin D deficiency causes or exacerbates disease.