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CORVALLIS, Ore. - Your best defense against influenza, by far, is to get the flu vaccine. Washing hands, a healthy diet and lifestyle are also important.

But after that, a growing body of research suggests the next best thing you should consider for the prevention of flu and other upper respiratory infections is to make sure you have adequate levels of vitamin D. Most Americans do not.

As one of the worst flu seasons in recent years spreads its misery across the nation, experts in the Linus Pauling Institute at Oregon State University say that more people may want to get their blood levels of vitamin D checked. If too low, they could consider supplements to reach optimal levels of this "sunshine vitamin" that both laboratory and epidemiological studies suggest can help reduce respiratory infection.

The winter cold and flu season corresponds - perhaps by coincidence, perhaps not - with the time of year when most people also get the least sun exposure and, as a result, drop to their lowest levels of vitamin D. It can be difficult in winter to get adequate vitamin D from diet alone.

"Vitamin D affects a wide range of immune functions, both innate and adaptive, that can help a person recognize and respond to both bacteria and viruses, not just the flu but many others," said Adrian Gombart, an OSU associate professor of biochemistry and biophysics, principal investigator with the Linus Pauling Institute and international expert on vitamin D and the immune response.

"The number of people in the U.S. with insufficient levels of vitamin D is probably above 60 percent, especially in the northern states, most of Europe and all of Canada," Gombart said. "This problem is critical in the elderly, who may get little of it in their diets, don't get outside as much, and synthesize vitamin D from sunshine at a rate only about 20 percent that of younger adults."

Vitamin D has anti-inflammatory effects, may improve vaccine response, and is important for the response of immune and epithelial or "barrier cells" in the lungs. Without adequate vitamin D, these cells don't adequately express cathelicidin, an antimicrobial peptide gene. Laboratory studies have shown that this antimicrobial peptide reduced both infection and inflammation, and protected mice against an influenza challenge.

"Many studies have been done, both in the laboratory and in clinical trials, and some have conflicting results," Gombart said. "One explanation may be that some study participants already had adequate levels of vitamin D. If you aren't deficient in this nutrient, adding more to your diet isn't going to offer much benefit. We still need more well-designed clinical trials with a vitamin D deficient population."

Many scientists believe that at least 32 nanograms per milliliter of vitamin D in the blood is a reasonable minimum, Gombart said, and some research has found increased protection against upper respiratory infection in people with levels around 38 ng/ml. But the level now considered insufficient, based primarily on bone health rather than other health outcomes, is less than 20 ng/ml.

The official RDA for vitamin D was recently raised, and is now 600 IU daily for most adults, 800 IU for the elderly. An intake of 2,000 IU per day for all adults and 400 IU for children should get most people to a blood level of 32 ng/ml or higher. But this is difficult to achieve through diet alone - a cup of vitamin D fortified milk, for example, has about 100 IU.

Historically, studies about adequate vitamin D were focused on bone health, including overt deficiency diseases such as rickets. Scientists now understand this vitamin plays a much larger role in many physiologic functions, especially an appropriate immune response.

There are estimates that one billion people around the world may be deficient, mostly in the temperate zones and higher latitudes, and any population with darker skin color also faces higher risk. Some experts say that in the U.S. more than 90 percent of black, Hispanic and Asian populations have insufficient levels. The primary source of this fat-soluble nutrient is a metabolic response to UV-B radiation in sunshine.  Diet plays only a limited role.

The regulation of cathelicidin by vitamin D, which was discovered by Gombart, is a unique biological pathway that can help explain vitamin D's multiple roles in immune function. This pathway exists only in two groups of animals - humans and non-human primates.  Its importance for their immune response against infection is highlighted by its conservation through millions of years of separate evolution.