Vitamin Information Center

Vitamin D is the key to preventing rickets and osteoporosis, but Rockefeller University scientists suspect it may also play a role in heading off atherosclerosis in people with chronic kidney disease. In a new clinical study, investigators at The Rockefeller University Hospital are examining patients with moderately reduced kidney function to investigate the effect of vitamin D therapy on endotoxemia, a condition that is common among those with renal disease and is widely viewed as a contributor to heart disease. The study, led by Instructor in Clinical Investigation Manish Ponda, is partially funded by a $25,000 grant from the Center for Clinical and Translational Science.

The high rate of atherosclerosis among patients with kidney disease is well documented but little understood by medical experts. Endotoxins, products of the natural breakdown process of bacteria, are a hot topic of clinical investigation with regard to both heart and kidney disease. “The number one killer among people with kidney disease is heart disease, just like in the rest of the population, except that in people with kidney disease, the heart disease exhibits an accelerated course,” says Ponda, a member of Jan Breslow’s Laboratory of Biochemical Genetics and Metabolism at Rockefeller. The research is an extension of earlier clinical work by Ponda that showed a high incidence of vitamin D deficiency among early-stage kidney disease patients.

Study participants — males and postmenopausal females between ages 50 and 80 with stage three chronic kidney disease and vitamin D deficiency — will be provided with thrice-weekly doses of vitamin D3, also known as cholecalciferol, the form of vitamin D produced by the body in response to sunlight. Participants will make three outpatient visits at intervals of four weeks each to The Rockefeller University Hospital, where investigators test for levels of endotoxins in response to vitamin D repletion.

The dose of vitamin D prescribed for the study — 30,000 international units per week — equals more than 20 times the intake recommended by the United States Department of Agriculture and approximately 10 times the amount in an average multivitamin supplement. The dosage is designated to safely reverse vitamin D deficiency.

If Ponda’s hypothesis — that vitamin D repletion will be accompanied by decreases in blood endotoxin levels — holds true, a larger, more-extensive, “progression” study will follow, to chart the connection over longer periods of treatment and in later stages of renal disease. “Kidney disease puts a person at significantly higher risk for cardiovascular disease, but it is often asymptomatic even as late as stage three,” says Ponda. “The more definitively we can characterize renal disease, the closer we are to effectively treating both it and its comorbid conditions.”

Hardly a week goes by, it seems, without a press release regarding a new vitamin D study appearing in my email box.

For example:

“Men with Low Vitamin D May Have Increased Risk of Heart Attack”
“Study Links Vitamin D to Colon Cancer Survival”
“Vitamin D Inadequacy May Exacerbate Chronic Pain”
“Low Vitamin D Levels May Worsen Osteoarthritis of the Knee”
“Low Levels of Vitamin D Associated with Depression in Older Adults”
“Study Links Vitamin D, Type 1 Diabetes”
“Vitamin D Linked to Reduced Mortality Rate in Chronic Kidney Disease”

Then, last Friday, came the uber-vitamin D press release:

“Low Vitamin D Levels Pose Large Threat to Health”

That study, published this week in the Archives of Internal Medicine, found a 26 percent increase in risk of early death from any cause among people with inadequate levels of vitamin D.

What’s going on? Why this sudden (or so it seems) interest in the “sunshine vitamin”? (The nickname comes from the fact that the vitamin is produced in the skin from sunlight.) And what are health consumers – especially here in Minnesota, where the low angle of the winter sun makes it difficult to sustain adequate vitamin D levels – to make of it all?

Old interest, new connections
Despite the current flurry of studies, research into vitamin D’s multipronged impact on human health “is not all that new,” said Kurt Kennel, M.D., an assistant professor of medicine at the Mayo Clinic in Rochester. Scientists have known since the 1970s that vitamin D’s effect on the body went beyond regulating calcium and helping to build strong bones.

Much of the past research, however, was confined to the laboratory. In recent years, thanks to better ways of assaying (or measuring) vitamin D in the body, scientists have been able to give it a more clinical face, linking it to the risk of developing different diseases.

In addition, aging baby boomers have developed a deep and personal interest in the bone-weakening disease osteoporosis.

“That put vitamin D on the map,” said Kennel.

A misnomer
To understand vitamin D’s ubiquitous role in the body, we need to stop thinking of it as a traditional vitamin.

“If we named it today, we’d call it a hormone,” said Kennel.

Like insulin, adrenaline, estrogen and other hormones, vitamin D is produced by a body organ (in this case, the skin). It’s then carried through the body by a fluid (blood) to other organs and tissues (the heart, brain, breasts, kidneys, muscles, and so on). At each of these destinations, vitamin D adeptly attaches itself to receptors on the DNA of genes in the cells’ nuclei.

As we’re now learning, the resulting effects appear to be remarkably beneficial, possibly protecting against heart disease, kidney disease, diabetes, osteoporosis, multiple sclerosis, certain types of cancers (including breast, lung and colon) and other major illnesses and conditions.

The latest study
In the newly published study – considered the most compelling evidence of vitamin D’s overall health benefits to date – a team of John Hopkins researchers analyzed vitamin D levels in more than 13,000 men and women aged 20 and older who participated in a large ongoing health survey conducted by the Centers for Disease Control and Prevention. The data was collected between 1988 and 1994.

To ensure comparable results, vitamin D levels were surveyed during the summer among participants living in northern states and during the winter among those in southern states.

All participants were tracked until Dec. 31, 2000, by which time 1,806 had died. Those whose vitamin D levels had been the lowest (less than 17.8 nanograms per milliliter of blood) had a 26 percent increased rate of death from any cause compared to those with the highest vitamin D levels (above 50 nanograms per milliliter).

Cardiovascular disease seemed to be the major factor in these deaths, although the study wasn’t able to determine with scientific certainty a cause-effect relationship between low vitamin D levels and heart attacks and strokes.

“In the past few months, several other papers have confirmed that low vitamin D levels are associated with increased risk of heart attacks and strokes,” said Erin Michos, M.D., one of the study’s lead investigators.

In fact, earlier this year, Michos and her team showed an 80 percent increased risk of peripheral artery disease among people with vitamin D deficiency.

It may not be long before vitamin D deficiency is added to the long list of risk factors for heart disease, she said.

What’s a consumer to do?
Vitamin D deficiency is, by some accounts, reaching epidemic proportions. A review article published in The New England Journal of Medicine last year reported that up to 50 percent of children and adults in the United States have insufficient levels (less than 20 nanograms per milliliter).

“Vitamin D deficiency is getting a lot more common because we’re getting more obese and sedentary, and we’re spending less time in the sun,” said Michos.

People who are over the age of 50, who have dark skin, or who wear clothing that covers most of their skin are also at increased risk. (The last two reasons, said Kennel, are partly why Minnesota’s Somali immigrants have higher-than-average rates of vitamin D deficiency.)

Both Kennel and Michos recommend that people boost their vitamin D levels by eating salmon, mackerel and other fatty fish and fortified dairy products. (Years ago, vitamin D used to be added to beer, but, alas, no longer.) You can also take cod-liver oil (yes, just as your great-grandparents did) and/or vitamin supplements.

Federal guidelines currently recommend that adults get 200 to 600 international units (IU) of vitamin D daily. Those recommendations are currently under review, said Kennel, and will most likely be upped.

The National Osteoporosis Society already recommends 800 to 1,000 IU to people aged 50 and older. And the Canadian Cancer Society, citing Canada’s northern latitude, recommends that adults living there take 1,000 IU of vitamin D daily during fall and winter.

Currently, most experts put the safe upper limit of vitamin D from supplementary sources at 2,000 IU per day. But that number, too, may be increased.

Out in the noonday sun
The best way to get vitamin D, of course, is to spend time in the sun. In a single 10-minute midday outing, your skin will produce about 10,000 IU.

Fortunately, your skin won’t let you overdose on vitamin D from the sun. But spending unprotected time in the sun increases your risk of skin cancer, which has also reached epidemic proportions in the United States.

“Unfortunately, the time of the day the dermatologist wants you to be out – the morning and the evening – is the worst time for your body to make vitamin D,” said Kennel.

If you think you’re at increased risk for vitamin D deficiency, talk with your physician about having your blood levels of the vitamin checked. You’ll then have a better idea of whether you need supplements.

And remember: Although the recent findings about vitamin D are intriguing and promising, the benefits are not yet proven.

Studies of other nutrients and hormones – vitamin E, vitamin A, and estrogen, to name a few – were also found to benefit the heart in observational studies. But when it came time for the clinical trials, not only did they fail to prevent heart disease, they actually increased the risk.

Stay tuned.

Chronic kidney disease patients may see their risk of death drop by one quarter if they take a form of vitamin D, a new study says.

In a study of more than 1,400 people with chronic kidney disease, those that were taking the drug calcitriol, a form of activated vitamin D, had a 26 per cent reduction in their risk of death versus those who were not on the drug. Overall, the patients on calcitriol had their risk of either death or dialysis due to a loss of kidney function fall by 20 per cent.

The study is published in the Journal of the American Society of Nephrology.

A healthy human body uses first the liver and then the kidneys to convert vitamin D obtained through diet and sunlight into an active form that the body can use. However, it is believed that patients with chronic kidney disease are unable to do complete the second step.

They are often prescribed activated vitamin D to help lower elevated levels of the parathyroid hormone, which can lead to a weakening of the bones. However, people with kidney disease often suffer from calcified, or stiff, blood vessels, which can lead to a host of cardiovascular problems. Vitamin D increases calcium levels in the blood, which doctors fear could exacerbate this problem.

“We did find that people who got the activated vitamin D drug did have a higher risk of having a high calcium level in the blood,” study author Dr. Bryan Kestenbaum of the University of Washington told Ctv.ca.

“But the overall amount of people that that happened to was relatively small, and the overall balance was that people who got the activated vitamin D drug survived longer.”

Kestenbaum speculated that vitamin D leads to decreased mortality rates because of its known ability to lower risk factors for cardiovascular disease, including high blood pressure, diabetes and inflammation.

He said that the next step in this field of research would be to conduct randomized clinical trials to confirm vitamin D’s effect on survival rates among patients with kidney disease.