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April 14, 2011

On Health:

Pitt experts discuss vitamin D

applesIncreasingly, studies have shown, people are seeking health-related information. A recent Pew Internet study found that 80 percent of Americans with Internet access turn to the web for answers to their medical and health questions.

But three-quarters of consumers fail to check how reliable and how current that information is, the study revealed.

In an effort to detangle some of the overload of health information that is out there, this occasional University Times series, On Health, is turning to Pitt experts for current — and reliable — information on some of today’s major health-related topics. A recent report that increased the recommended dietary intake levels for vitamin D, coupled with research that hints at a wide range of benefits, has put the so-called “sunshine vitamin” into the spotlight.

VITAMIN D

Pitt experts examine the issues

Vitamin D is needed for bone growth and strength. The vitamin helps the body absorb calcium and is important in protecting against rickets and osteoporosis. According to the National Institutes of Health, the vitamin also modulates cell growth and plays a role in neuromuscular and immune function and in reducing inflammation.

Last fall, the Institute of Medicine (IOM), the health arm of the National Academy of Sciences, issued a report saying that most people need no more than 600 international units (IUs) of vitamin D daily for bone health, although people 71 and older may need 800 IUs.

The IOM also determined an upper safe boundary of 2,500 IUs daily for children ages 1-3; 3,000 IUs for children 4-8 and 4,000 IUs per day for everyone else.

The IOM determination has been controversial. Some doctors criticized as too low the IOM’s finding that blood levels of 20 nanograms per milliliter (ng/ml) of 25-hydroxyvitamin D, or 25(OH)D, indicate sufficient vitamin D. Among them, a pair of Harvard public health researchers took the IOM recommendation to task, citing an earlier International Osteoporosis Foundation recommendation of approximately 30 ng/ml for optimal fall and fracture reduction and intake of 800-1,000 IUs for people age 60 and older.

Pitt epidemiology faculty member Jane Cauley, whose research was included in the literature the IOM considered in developing the new guidelines, said she wasn’t surprised that some colleagues thought the IOM’s guidelines were too low. “Those guidelines emphasized skeletal health over other benefits,” she said. “So there’s disagreement between those who say 20 is deficient and those who say it’s 30. The IOM suggests that the majority of risks are in individuals with blood levels of less than 20.”

Cauley said her observational studies on the relationship between vitamin D levels and fractures in older men and women found no increased risk of hip fractures until blood levels were less than 20. “These data support the IOM recommendation,” she said.

Critics also noted that the IOM’s recommendations don’t take into account the vitamin’s other potential benefits. However, the IOM defended its narrower recommendation, stating that its committee found conflicting results among the hundreds of studies it reviewed on other possible health benefits.

While the report stopped short of touting vitamin D as beneficial in protecting against cancer, heart disease, autoimmune diseases and diabetes, the IOM committee acknowledged that studies on these outcomes “point to possibilities that warrant further investigation,” although conflicting results “do not offer the evidence needed to confirm that vitamin D has these effects.”

“There’s a lot of interest in looking at the non-skeletal issues,” Cauley said, citing as an example a new study by the National Cancer Institute and the National Heart, Lung and Blood Institute that seeks to determine whether taking 2,000 IUs of vitamin D daily can prevent cardiac events and cancer.

“There’s lots of interesting research, on immunity, for example,” Cauley said, citing early 20th-century sanitariums where tuberculosis patients’ treatment included exposure to fresh air and sunlight. “Did the resulting vitamin D that was produced help?

“There’s a lot of biology supporting extra-skeletal benefits, but the literature is not there yet,” Cauley said. “But promising data suggest that might be the case.”

She noted as well that there is additional research currently under review that suggests optimal vitamin D levels might differ by race.

For more than a decade Pitt pediatrics professor Kumaravel Rajakumar has been researching vitamin D with an emphasis on its role in minority health disparities in children. His work also was among the studies IOM considered in making its recommendation.

One of Rajakumar’s earlier studies, involving 41 healthy local African-American children ages 6-10, researched the effects of supplementing their daily diets with 400 IUs of vitamin D for a month.

He found that 49 percent of the children had insufficient blood levels of vitamin D at the start of the study. Although the supplements increased the level of the vitamin in the children’s blood, 18 percent continued to have insufficient vitamin D levels at the end of the month.

“We’re all capable of making vitamin D in the skin,” Rajakumar said. But darker-skinned individuals are at greater risk of failing to get enough vitamin D. “Skin color makes a difference,” he said. “Melanin is a natural sunscreen and a black kid may need six-10 times the exposure that a lighter-skinned child might need to make the same amount of D.”

Geography and the time of the year matter as well.

In another observational study assessing vitamin D levels in local children, Rajakumar took into account season, race and diet. While most kids were meeting the 400 IU recommendation as a mean of the cohort, “a significant proportion were insufficient,” Rajakumar said, adding that blood levels of vitamin D were lower in winter.

He explained that the ultraviolet wavelength in sunlight that the body needs in order to produce vitamin D is very narrow, and is more available in summer than it is in the winter when the sun’s rays are more oblique. Above 35 degrees latitude (Pittsburgh is at approximately 40 degrees), people are more vulnerable to low levels of D, he said. “We can make enough in summer to ride us through the winter … but if you didn’t have enough summer banking, it can’t ride you through the winter.”

Research is continuing to determine optimal intake levels. While Rajakumar said he finds the new higher IOM recommendation a positive move, it still needs to be shown that 600 IU is sufficient, especially for dark-skinned children living in the north. “I think that there needs to be more work in that area,” he said.

Rajakumar stressed the importance of preventing and treating childhood vitamin D insufficiency in order to prevent osteoporosis later in life.

In addition to vitamin D’s benefits to bone health, which are related to its ability to help the body absorb calcium, vitamin D receptors are expressed in a variety of tissues including immune, vascular, pancreatic and brain cells, Rajakumar said, adding that optimizing vitamin D levels can make local changes within those cells. He noted that there are indications that vitamin D can play a role in improving insulin secretion, glucose utilization and immune function.

Geographic differences have been noted in rates for diseases such as multiple sclerosis and prostate cancer, he said, noting, “Sunlight is the difference, although there could be other confounding factors. Some believe it could be D.”

Observational data also correlates that people with low vitamin D levels are more prone to upper respiratory infections or cardiovascular disease, although he said the dosage necessary for avoiding those negative outcomes is not known.

Pitt researchers also are looking into the effects of vitamin D in the womb. Epidemiology faculty member Lisa Bodnar said when she first read about vitamin D in relation to pregnancy outcomes five years ago, “there seemed like a tremendous number of research gaps, yet it seemed very plausible that vitamin D could be contributing to adverse outcomes.”

In addition to determining the prevalence of vitamin D deficiency among pregnant women, researchers continue to investigate whether vitamin D supplements may decrease the risk of negative pregnancy outcomes such as pre-eclampsia and growth restrictions. Bodnar said she also is beginning to examine genetic components to determine whether there are specific genetic variations that may relate to vitamin D status.

Vitamin D levels may influence pre-term birth, a condition that is related to infant death and disability. “No one has identified many risk factors for it,” Bodnar said. Possible connections to pre-eclampsia and inflammation also are being examined, to determine whether low vitamin D may be related to systematic inflammation and whether inflammation could be a factor that leads to pre-term birth or pre-eclampsia.

Vitamin D levels have been related to diabetes risk in other research, Bodnar said, adding that one of her students is analyzing whether there also may be a relationship between vitamin D and blood glucose levels in early pregnancy, with an eye toward better understanding gestational diabetes.

The vitamin also may play a role in the risk of Caesarean delivery, Bodnar said. “Because D is important for muscle contraction, deficiency has been related to frailty and weak muscles,” she said. “It’s plausible that a uterus without as much D and calcium may not contract as well and a woman in labor may not progress and therefore need a Caesarean,” she said. “That’s very preliminary right now.”

Vitamin D deficiency is widespread among pregnant women, she noted. Although more than 90 percent of pregnant women take vitamins by the end of their pregnancy, Bodnar found that a large proportion of pregnant women remained vitamin D deficient, and that black women were more likely to have low vitamin D levels than white women.

“The myth is that because women are taking prenatal vitamins, there should be no deficiency,” she said. However, Bodnar said she found “more than 90 percent of black women were deficient in vitamin D. The propensity was toward deficiency in white women as well, although not to the same degree.”

In addition, there was a very clear seasonal change in vitamin D status, Bodnar said. “In summer and early fall levels were higher, but the levels really declined in winter and spring.”

Bodnar recently presented research that showed poor vitamin D status may be a risk factor for pre-term birth among black women.

Given that both vitamin D deficiency and pre-term birth are more common in black women, that finding may help explain why pre-term birth is more common in black women, she said.

Bodnar is especially interested in investigating how vitamin D may play a role in contributing to racial disparities in pregnancy outcomes. “If we could improve vitamin D status, it would have more of an impact on black women and potentially reduce that disparity,” she said. “That’s where I think this pregnancy research will have the biggest impact.”

Bodnar agreed that the IOM’s increased recommendation “was a move in the right direction.” However, some studies suggest a U-shaped curve when it comes to vitamin D’s association with certain outcomes — very high levels seem to increase risk.

A 2010 study of babies born small for their gestational age found such a curve. Similar results have been found in other areas, such as risk of fractures and falls.

“Knowing where is the nadir of the risk curve is important,” she said.

Given that there could be negative effects from ultra-high doses, “I think proceeding cautiously is important. We want to make sure we are giving people the best advice that we can.”

—Kimberly K. Barlow


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