Those connections have not yet been proved, but now studies on the relationship between vitamin D and serotonin production are taking researchers down a new path.

But in recent years, the efficacy of those supplements has been widely questioned, while other research has explored possible connections between vitamin D and heart health, cancer prevention, and other health benefits.

When you think of vitamin D, you may think of bone health. For years, doctors have recommended vitamin D and calcium supplements to guard against fractures and osteoporosis.

A growing body of evidence suggests that vitamin D — present in some foods and produced naturally when skin is exposed to sunlight — regulates the enzyme that converts the amino acid tryptophan into serotonin, a neurotransmitter believed to help regulate moods and direct brain development while in the womb.


“It is very important for guiding [where] neurons . . . go in the brain and how they shape the structure and the wiring of the brain,” said researcher Rhonda P. Patrick. “Without adequate serotonin in that developing fetus, the brain . . . doesn’t develop normally.”

Patrick, a postdoctoral fellow at Children’s Hospital Oakland Research Institute in Oakland, Calif., said the degree to which vitamin D regulates serotonin isn’t yet clear. But psychologists and neuroscientists have established the effects of low serotonin by restricting tryptophan entering the brains of human test subjects, she said.

“What happens is their long-term decision making shuts down,” she said. “They become impulsive and aggressive, angry, unhappy. They have difficult time interpreting people’s facial expressions.”

Vitamin D is naturally present in some foods, including fatty fish such as mackerel, salmon, and tuna, and in small amounts in cheese, egg yolks, and beef liver, according to the National Institutes of Health. But most vitamin D in the human diet comes from its addition to foods such as milk, orange juice, and breakfast cereals.


Because vitamin D regulates about 1,000 different types of genes in the body — roughly 5 percent of the human genome — Patrick and her mentor, Bruce N. Ames, a senior scientist at Children’s Hospital Oakland Research Institute, believes the nutrient may play a much larger role in our health than previously realized.

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Dr. Walter Willett, chairman of the nutrition department at the Harvard School of Public Health, said that the hypothesis suggests many avenues for further research.

“This work by Ames and Patrick is significant because it describes a potential pathway linking vitamin D with serious mental conditions, and may explain some of the features of these diseases,” Willett said in an e-mail.

Researchers are working to confirm Ames and Patrick’s hypothesis in the lab. Mark R. Haussler, a professor at the University of Arizona College of Medicine — Phoenix, and Peter Jurutka, an associate professor at Arizona State University, have conducted experiments that support the hypothesis, Haussler said.

In successive experiments using synthesized DNA, then cells from human kidneys, then cells from the brains of rats and of humans, Haussler and Jurutka established that vitamin D produced effects consistent with Patrick and Ames’s hypothesis: It enhanced the ability of the brain cells to produce serotonin by anywhere from double to 30 times as much, Haussler said.

Haussler said a better understanding of how to regulate serotonin production could have a “huge impact, and all the way across the life span.” Haussler speculated that regulating serotonin in developing brains could potentially affect the development of autism or attention deficit hyperactivity disorder.


Some benefits of vitamin D have been known for generations, Haussler said, though they might have been described in different terms.

“When I was young, my mother would say, ‘Mark, go out in the sun; you’ll feel better,’ ” Haussler said. “Well, you know, I usually did, and that’s a common-sense-type thing, but why? Why do we feel better when we go out in the sun? Sun makes vitamin D in your skin.”

But too much sun can also lead to skin cancer, he cautioned, and not all sun exposure will help produce vitamin D. In New England during the winter, the sun is too low on the horizon to help generate the production of vitamin D.

Doctors and researchers said that in this region and many others, it is beneficial to take a vitamin D supplement, at least during winter months, but controversies have arisen in recent years about the use of vitamin supplements and the tools for measuring vitamin D deficiency.

Late last year, a widely discussed editorial in the Annals of Internal Medicine encouraged the public to “stop wasting money” on vitamin and mineral supplements that had not been proved to prevent or slow the development of chronic diseases.

That editorial included a caveat that vitamin D supplementation remained “an open area of investigation, particularly in deficient persons” but nevertheless concluded that “current widespread use [of vitamin D supplements] is not based on solid evidence that benefits outweigh harms.”


Also last year, a study from Massachusetts General Hospital found that many of the 70 percent to 90 percent of African-Americans diagnosed as vitamin D deficient may actually have healthy levels of the vitamin — and are not deficient — because they are genetically disposed to carry more of the “free” form of the nutrient.

Willett, of the Harvard School of Public Health, said the anti-supplement editorial “was unhelpful as it lumped together a very wide range of doses and conditions.”

Willett said many Americans do not get enough vitamin D from diet and sun exposure and should take a supplement. His recommendation included African-American adults because, he said, science has not yet determined which forms of vitamin D benefit specific organs, and the “free” form may not be helpful in all instances.

There is no universal agreement about the proper dosage, but Willett recommends 1,000 international units per day for most adults. Patrick said that before taking a supplement, people should get tested and consult their physicians.

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Jeremy C. Fox can be reached at jeremy.fox@globe.com. Follow him on Twitter @jeremycfox.