Our main article describes how vitamin D protects us against tuberculosis. It turns out that identifying and understanding the microbiological mechanisms of the innate immune response, and the roll of vitamin D in this ancient defense system, required an extraordinary international collaboration. A total of 22 scientists in 10 medical schools and research centers, including one pharmaceutical company, in both Germany and the United States, participated in the investigation. To learn more about the technical details, click here. "Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response" Science DOI: 10.1126/science.1123933. This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

By Benjamin V. Treadwell, Ph.D.

Vitamin D and the phrase "strong bones" are closely identified in the minds of consumers, thanks primarily to the marketers of milk. Indeed, Vitamin D is a steroid hormone first discovered to be necessary for proper bone formation. Now, scientists are beginning to realize this micronutrient is necessary for numerous vital biological functions, including protection from tuberculosis. (Click here for additional information on vitamin D.

Scientists have long puzzled over the fact that low blood levels of vitamin D are associated with increased incidence of tuberculosis. A group of investigators recently made a significant discovery that may help explain the connection. It has been known that certain ethnic populations, such as African-Americans, have a significantly higher incidence of tuberculosis than the general population. It also became known that pigmented skin interferes with vitamin D synthesis. This is particularly evident in dark-skinned individuals who live in areas of decreased sun exposure. The vitamin D content in their blood is much lower than in that of their more fair-skinned counterparts (who nevertheless can have dangerously low vitamin D levels if they live in areas of minimal sun exposure, especially the aged).

The Innate Immune System Connection

The explanation for the vitamin D-tuberculosis correlation lies in the innate immune system. This part of the immune system is ancient, dating back 500 million years to the horseshoe crab. This defense acts almost instantly to destroy pathogens (unlike the much slower adaptive immune system, which takes weeks to be fully activated).

Most of us are more familiar with the adaptive immune system, which responds to pathogens by producing neutralizing antibodies and other pathogen-fighting agents. The adaptive immune system is activated in response to specific vaccines, such as those for flu, polio, measles, and mumps. Although this system provides a potent defense against disease, it has a major drawback, in that it takes weeks to be fully activated.

In contrast, the way the innate immune system works is that we are born with cells that contain specialized structures known as Toll-like receptors (TLRs). These receptors participate in the recognition of an invading pathogen. The recognition involves the binding of the TLR to a specific pattern of molecules exhibited on the surface of the pathogen. In other words, the pathogen wears a specific type of clothing that the TLR recognizes and binds to, like a key fitting a specific lock. Once recognized, the TLR forms a tight complex with the pathogens, and sets off a barrage of activities to destroy the pathogen (click here for more details on the innate immune system).

The investigators found that a specific type of white blood cell involved in immune-defense, the monocyte, plays a key role in protecting us from the tuberculosis bacterium. The TLR on the surface of the monocyte recognizes and binds to the specific pattern of molecules on the bacterium's surface. This lock-and-key interaction triggers a specific set of reactions in the monocyte. One effect is the immediate synthesis of receptors on the monocyte that bind a specific form of vitamin D. Another is to make more of that form of vitamin D. Now the monocyte is geared-up to do the incredible: produce its own antibiotic to kill the pathogen. A series of biochemical reactions within the monocyte culminates in the production of a specific protein called cathelicidin, which in turn destroys the tuberculosis bacterium.

The investigators took this experiment a step further. In cell-culture studies, they compared monocytes incubated in serum from African Americans with low levels of vitamin D to those incubated with serum from people with normal levels of the vitamin. They found that the former had much lower production of the anti-bacterial agent, cathelicidin.

What are the implications?

The above story illustrates the potential importance of the innate immune response in human health. Perhaps more importantly, it is a wake-up call for the heretofore unknown importance of vitamin D in protecting our cells and tissues from disease.

It also allows for speculation on other diseases associated with low serum levels of vitamin D. For example, prostate cancer is one such low-D associated disease that is currently under investigation. Interestingly, an association between a specific virus and prostate cancer was recently reported. Is it possible that this too may involve the innate immune system that is impaired due to a deficiency in vitamin D or a defect in the vitamin's receptor?