Research Suggests Strong Immune Role for Vitamin D

by Kayt Sukel

March 9, 2009

Vitamin D, a micronutrient we absorb from the sun’s rays, has long been known to be beneficial to bone health, preventing childhood diseases such as the bone-softening rickets. But new research suggests that the micronutrient’s reach may be much deeper—it may play a pivotal role in the development and maintenance of the human immune system.

In a review published in the December 2008 issue of Breastfeeding Medicine, researchers from the Medical University of South Carolina (MUSC) argue that insufficient vitamin D levels, particularly in mothers and children, have led to a nutrient deficiency epidemic with potentially dire consequences from a public health perspective.

From sunshine to hormone

Vitamin D is often lumped together with other micronutrients such as vitamins A, B and C. But there are some important differences between them.

“In some senses [vitamin D is] not a vitamin at all, at least in the sense that it is not often found in the foods human beings eat,” says Bruce Hollis, the director of pediatric nutritional sciences at MUSC. “Even if you eat a balanced diet, there is no impact on the amount of vitamin D you take in.”

Instead, Hollis argues, the body mostly receives this micronutrient from exposure to sunlight. “It’s not all that different from how plants use photosynthesis to get the nutrients they need,” he says. “Our skin absorbs vitamin D from the sun and then the body converts it to a hormone.”

To get to that state, vitamin D goes through several complex biochemical steps, eventually transforming into a hormone called calcitriol. And ample evidence suggests that calcitriol interacts with specific vitamin D receptors in both the brain and the immune system. When the human body has insufficient vitamin D levels, immune functions mitigated by calcitriol and vitamin D receptors suffer.

At work on genes

More than 100 years ago, in 1903, Danish physician Niels Finsen took home the Nobel Prize for his pioneering treatment of tuberculosis with ultraviolet light. Though the cellular mechanisms of the treatment were unknown at the time, scientists now understand that calcitriol played a part in the so-called heliotherapy’s beneficial effects.

But as the human genome project became a reality, nearly 1,000 genes were found with vitamin D receptors that calcitriol might turn on and off. Closer looks at some of these individual genes have shown that hundreds are directly influenced by levels of vitamin D.

“There are now hundreds of genes that have been shown to be affected by vitamin D,” says Bruce Ames, a molecular biologist at the Children’s Hospital Oakland Research Institute. “And these genes span a range of functions. Certainly the immune system is one of the big systems that vitamin D is interacting with, but there may be many other kinds of genes where vitamin D is also playing some role.”

Direct effects on immune function

In a report published in 2006 in Science, Hollis and colleagues at the University of California, Los Angeles, demonstrated that vitamin D triggers an innate immune response in humans. The researchers showed that insufficient vitamin D levels made it more difficult for cells to activate toll-like receptors (TLRs), a type of receptor that kicks off a direct immune response to bacterial threats.

“It was a very elegant study,” says Carol Wagner, a pediatric researcher at MUSC. “[The researchers] were able to show that activation of TLRs is affected by a person’s vitamin D status. With lower levels of the vitamin, the cells could not turn on the message to start the immune response. But once vitamin D was added, [the cells] were able to turn the whole process on and correct it.”

Since then, dozens of studies have linked insufficient vitamin D levels with disease states including bone problems, tuberculosis, multiple sclerosis, some cancers, cardiovascular disease and diabetes. Simply put, insufficient vitamin D levels impact the genetic and molecular pathways of the immune system, leading to cell breakdown and disease.

“Many of these chronic diseases have flourished in the past few decades,” says Hollis. “And one of the reasons may be a chronic deficiency of vitamin D due to lifestyle changes.” Those changes include lack of exposure to sunlight from more sedentary indoor lifestyles as well as increased use of ultraviolet-blocking creams and clothing.

Treating the deficiency

Hollis and Wagner, co-authors on the Breastfeeding Medicine review with Sarah Taylor, are now involved with a longitudinal study of pregnant and lactating women that is examining the influence of low vitamin D levels in mothers on their infants after delivery. Though the study is ongoing, Hollis contends that we need to increase vitamin D levels for people across the board, particularly those with darker skin pigments who need more extensive sun exposure to reach optimum status.

“We’re already treating all of these complex diseases with pharmacology,” he says. “But we’re still not treating the deficiency. Doing so could give us a very different approach to treatment.”

Wagner agrees. “We’ve developed wonderful antibiotics that can treat many diseases. But the immune infrastructure has to be there first,” she says. “And we’re now seeing what happens when we are deficient in an essential vitamin like vitamin D—autoimmune diseases, cancers, cardiovascular disease. How can you explain all of those diverse diseases? One of the common glues is very likely insufficient vitamin D levels. And we need to think more about how to best rebuild this cornerstone of our innate immune system.”