Vitamin D supplements are immunosuppressive

For many years, vitamin D supplements have been recommended in high quantities for patients with a range of problems. However, this article describes how the most recent high-quality studies on vitamin D supplementation no longer support such claims. Nevertheless, many patients who take vitamin D supplements still report feeling better. This begs the question: Why!?

It is important to take a closer look at “vitamin” D. The various forms of vitamin D are not actually vitamins in the traditional sense. Instead, all forms of vitamin D are secosteroids, sharing a close structural and functional resemblance to steroids.

My research, done in conjunction with the non-profit foundation Autoimmunity Research Foundation, suggests that, when taken as a supplement, the secosteroid vitamin D acts in a manner similar to that of other steroid-based medications. These medications, such as prednisone, work by slowing the activity of the immune system.

2013-Proal-Spain.001Other studies additionally support the possibility that the form of vitamin D derived from food and supplements – 25-hydroxyvitamin D or 25-D – is immunosuppressive. Several studies show that 25-D slows the activity of immune system proteins and blood cells. Researchers studying the effects of 25-D in patients with multiple sclerosis have concluded that “vitamin D has multiple immunosuppressant properties and that, on the whole, vitamin D confers an immunosuppressive effect.”

Immunosuppressive medications or substances have been shown to successfully palliate symptoms in the short-term, but have negative effects on a patient’s long-term health. One reason for this is that any medication that slows the immune response allows pathogens in the microbiome to better survive. This can promote the dysbiosis or imbalance of the microbiome often observed in inflammatory disease.

When autoimmune disease was thought to result from the immune system attacking “self,” immunosuppressant medications were believed to help control this “overactive” immune response. However, as I describe here, the theory of autoimmunity is being re-evaluated. It is now more likely that autoimmune disease results from infectious processes and microbiome dysbiosis.

Under such conditions, the symptoms of an inflammatory disease result in large part from a “battle” between the immune system and chronic pathogens. As the immune system strives to target and kill these pathogens, it secretes a host of immune cells that generate inflammation. While the release of these inflammatory molecules makes a person feel temporarily worse, it increases the likelihood that the pathogens making them ill might be successfully killed.

Thus, the short-term symptom “improvement” often experienced by patients taking vitamin D and other immunosuppressive substances does not result from improved health. Instead, as the immune system slows, the patient becomes more likely to acquire other pathogens over time. Indeed, patients taking immunosuppressive medications often suffer from increased periods of relapse and are are more likely to develop new symptoms.

To minimize vitamin D’s immunosuppressive effects, I recommend that blood-borne 25-D be kept below the consensus immunosuppressive level of approximately 50–60 nmol/L to optimize immune function and overall health. I (Amy) have successfully kept my 25-D levels in this range by avoiding vitamin D supplements and any foods to which vitamin D has been artificially added. I do eat moderate amounts of foods that naturally contain vitamin D, such as eggs and fish.

The following excerpt is taken from a book chapter I wrote for the 2015 textbook Infection and Autoimmunity. It describes vitamin D’s immunosuppressive properties in more detail:

One of the most common supplements used to palliate inflammatory symptoms is vitamin D or cholecalciferol, a precursor for the secosteroid 25-D. While vitamin D has long been viewed solely as a nutrient, vitamin D metabolites are actually potent secosteroids. While the metabolism of a vitamin is characterized by a first-order mass-action model, metabolism of the vitamin D secosteroids is instead governed by layers of feedback and feed-forward transcriptional pathways that are tightly regulated in H. sapiens. This calls into question whether the word vitamin accurately communicates any of the primary activities of this supplement.

The various forms of vitamin D exert their actions via the Vitamin D nuclear receptor or VDR. While proper functioning of the VDR is vital to a plethora of activities necessary for optimal human health, an increasing number of studies show that artificial supplementation of vitamin D metabolites does not result in optimal VDR activity. Under conditions of health, the VDR is activated by 1,25 dihydroxyvitamin-D (1,25-D). Yet,1,25-D concentrations often increase in patients as they become ill. Elevated 1.25-D can subsequently interfere with the ability of key nuclear receptors to correctly express the antimicrobial peptides (AMPs) under their control.

Elevated concentrations of 25-D in the blood cause additional immunosuppression by a number of mechanisms. Dickie et al. found that 25-D slows the activity of several toll-like receptors including TLR2, TLR4, and TLR9. A study of multiple sclerosis demonstrated that the supplement effectively slowed the immune activity of peripheral blood mononuclear cells. Indeed, Arnson et al. argued that vitamin D has multiple immunosuppressant properties and that, on the whole, vitamin D confers an immunosuppressive effect.

Over the past decade we performed several in silico experiments that suggest that blood-borne 25-D is able to directly bind into the VDR binding pocket to slow receptor activity. Much like the microbial ligands that slow innate immunity by interfering with VDR activity, this antagonism would result in a significant decrease in the expression of the antimicrobial peptides and TLR2. This immunosuppressive effect progressively increases as higher doses of vitamin D are administered, resulting in the J- or U-shaped curves evident in so many of the clinical trials. The resulting decrease in innate immune activity enhances pathogen survival, and homeostasis of the microbiome is more easily disrupted.

We have subsequently argued, with increasing urgency, that any subjective or objective improvements associated with vitamin D supplementation in the short term result from its ability to decrease the immunopathology associated with an effective innate immune response to elements of a patient’s microbiome.

Blood-borne 25-D likely provides symptomatic relief by acting in a manner similar to the immunosuppressive medications described earlier, the use of which has been associated with high rates of relapse and instability over time. Thus, while we are accustomed to the hypothesis that high levels of vitamin D supplementation are necessary to curb the current epidemic of chronic disease, the opposite may instead be true. Vitamin D is added to an increasing variety of food products and is more frequently used in the clinic, but the incidence of nearly every chronic condition has, in fact, increased. To minimize potential harm, we believe that blood-borne 25-D must be kept below the consensus immunosuppressive level of approximately 50–60 nmol/L to optimize innate immune function and overall health.