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Vitamin D & HIV
  Vitamin D: From muscle strength to immunity, scientists find new vitamin D benefits—cancers, immunity, diabetes
Janet Raloff
Science Magazine, Oct 16, 2004, Vol 166, No 16
Note from Jules Levin: is the bone loss problem in HIV due to HIV or lack of adequate intake of vitamin in the patient populations affected by HIV? I'm not sure if this question has been studied.
The story of vitamin D would appear simple. Take in enough sun or drink enough fortified milk to get the recommended daily amount, and you'll have strong bones. Take a supplement, if you want insurance. But recent studies from around the world have revealed that the sunshine vitamin's role in health is far more complex. More than just protecting bone, vitamin D is proving to preserve muscle strength and to give people some protection against deadly diseases including multiple sclerosis (MS), diabetes, and even cancer.
Outdoor activities—even reading—build vitamin D in people as long as enough of a person's skin is exposed to the sun.
What's now clear is that vitamin D is a potent force in regulating cell growth, immunity, and energy metabolism, observes David Feldman of Stanford University School of Medicine. He's the editor of a new 1,300-page compilation of research findings from more than 100 labs working on this substance (2004, Vitamin D, Academic Press). Not only is the vitamin gaining increasing respect as a governor of health, he notes, but it's also serving as the model for drugs that might tame a range of recalcitrant diseases.
Ironically, observes bone-metabolism specialist Robert P. Heaney of Creighton University Medical Center in Omaha, Neb., vitamin D is a misnomer. "A vitamin is an essential food constituent that the body can't make," he explains, but people have the capacity, right in their skin, to produce all the vitamin D they need from a cholesterol-like precursor.
Once vitamin D is available, the body converts it first into 25-hydroxy vitamin D and then into 1,25-dihydroxy vitamin D (1,25-D). This final form, which is actually a hormone, is the only active variety. Researchers loosely refer to all three substances in this biochemical cascade as "vitamin D."
The human body can generate 10,000 to 12,000 international units (IU) of vitamin D from a half-hour of summer-sun exposure. The National Academies recommend that adults, depending on their age, get from 200 to 600 IU of the vitamin each day.
In practice, however, most people in the United States get a daily intake from food and sun exposure well below that recommended intake, especially during winter. People living in the United States and Europe or farther from the equator have trouble getting enough sun to maintain adequate blood concentrations of the vitamin. When people heed dermatologists' warnings about preventing skin cancer by limiting sun exposure and using sunscreen, they also reduce their vitamin D production.
By studying the subtle effects of vitamin D deficiency and boosting animals' exposure to it in laboratory tests, researchers have been slowly teasing out the vitamin's myriad benefits.
Muscling in
Leg weakness is a common symptom of severe vitamin D deficiency. Five years ago, nutritional epidemiologist Heike A. Bischoff-Ferrari began wondering whether vitamin D affects muscle function in apparently healthy people as well. She was particularly concerned about senior citizens, who typically suffer from an inexorable muscle wasting that begins by age 40 (SN: 8/10/96, p. 90: http://www.sciencenews.org/pages/sn_arch/8_10_96/bob1.htm). So, she measured vitamin D blood concentrations in elderly men and women and found that individuals who had higher readings also had greater thigh strength.
Bischoff-Ferrari and her team at the University of Basel in Switzerland then launched an intervention trial with 122 women in their mid-80s. The researchers administered 1,200 milligrams of calcium to all the participants, and another 800 IU of vitamin D per day to half of them. At the end of 3 months, each woman was tested for leg strength and rated on how easily she could get up from a chair, walk around an object, and sit back down.
Not only did vitamin D¨Csupplemented women perform dramatically better on these tests, but they sustained only about half as many falls during the trial, according to the researchers' report in the February 2003 Journal of Bone and Mineral Research.
Bischoff-Ferrari, now at the Harvard Medical School in Boston, teamed with other Boston researchers to analyze past studies of falls in elderly people. Falls are a leading cause of fracture and disability in that population and account for U.S. medical bills exceeding $20 billion a year.
The researchers reevaluated five previously published vitamin D¨Csupplementation trials that together included more than 1,200 elderly people. Overall, a daily vitamin D intake of at least 400 IU cut a woman's risk of being injured in a fall by more than 20 percent, and higher doses had an even greater effect. Bischoff-Ferrari notes, "We showed that to get the best protection from falling, you likely have to get 800 units or more [daily]." She and her colleagues reported the findings in the April 28 Journal of the American Medical Association.
More recently, the team combed through a national diet-and-health survey of some 4,100 men and women 60 years and older. The researchers report in the September American Journal of Clinical Nutrition that blood concentration of vitamin D directly correlated with leg strength and function in these people.
Attack mode
Other correlations between vitamin D and health have captured researchers' attention. Kassandra L. Munger of the Harvard School of Public Health in Boston recently presented evidence of what appears to be a protective effect of vitamin D against MS. In two ongoing studies of 187,500 U.S. nurses, women getting at least 400 IU of vitamin D per day showed only 60 percent the risk of developing MS compared with women getting less of the vitamin, Munger and her colleagues reported in the Jan. 13 Neurology.
These findings not only confirmed a link seen earlier in animals but also fit with several long-standing geographic observations. The incidence of MS and other autoimmune diseases—in which a person's immune system attacks parts of his or her own body—tend to be rare near the equator, where ultraviolet light from the sun is intense and people produce abundant vitamin D.
For 2 decades, scientists have known that certain immune cells in the blood possess receptors for 1,25-D, the active form of vitamin D. To probe why, Margherita T. Cantorna of Pennsylvania State University in University Park and her colleagues incubated white blood cells with 1,25-D. The team found that the hormone inactivates a type of immune cell called a killer T lymphocyte. These are the cells that launch immune attacks against material invading the body, as well as native cells that have become infected or malignant. Killer T lymphocytes also drive autoimmune diseases.
Over the years, Cantorna's team has shown in animal models of MS, lupus, inflammatory bowel disease, and type 1 diabetes that autoimmune symptoms diminish or disappear after the animal receives either 1,25-D or chemical analogs of it. The group has even shown, in a mouse study, that such drugs can prevent rejection of a transplanted heart.
Cantorna and others have turned to 1,25-D analogs for potential therapeutic applications of vitamin D because excessive amounts of 1,25-D can raise blood-calcium concentrations to toxic levels, which can lead to kidney stones and heart disease.
The analogs that drug companies have devised mimic many of the vitamin's effects on cells but produce less of an increase in blood calcium. Cantorna explains that her animal studies have benefited from the analogs because the 1,25-D doses needed to have an anti-autoimmune effect "were pushing the envelope of what's safe." Companies are now beginning trials with such drugs in patients with autoimmune diseases.
Recently, Cantorna has focused on the mechanism of vitamin D's immune benefits. Her findings indicate that the vitamin's availability during T cell development influences how the mature cells operate. Vitamin D deficiency leads the cells to produce agents that are more reactive to other cells than are those produced when the killer T cells grow up with abundant vitamin D.
Cantorna suspects that once full-blown autoimmune disease appears, "you've already lost your window of opportunity to change the kind of T cells that develop."
The immune reaction known as inflammation can also be a leading player in gum disease and tooth loss (SN: 2/24/01, p. 116: Available to subscribers at http://www.sciencenews.org/articles/20010224/fob2.asp). Low blood concentrations of vitamin D were linked to gum disease in a study of 11,200 men and women who had taken part in the federally sponsored National Health and Nutrition Examination Survey, Thomas Dietrich of Boston University's dental school and his colleagues report.
The rate of loss in tooth-gum attachment was 25 percent higher among those participants with the least vitamin D compared to those with the most vitamin. Since poor attachment correlated with low vitamin D even when bone density was taken into account, the investigators say that the observed effect probably stemmed from the vitamin's effect on immunity. They conclude in the July 1 American Journal of Clinical Nutrition that vitamin D "may be important for preventing tooth loss."
Double trouble
Like autoimmune diseases, several cancers—though not skin cancer—become less common in populations the closer they are to the equator. Recent research suggests that vitamin D underlies that geographic pattern, says JoEllen Welsh of the University of Notre Dame (Ind.). In the July 2003 Journal of Nutrition, she and her colleagues reviewed laboratory evidence that the vitamin signals colon, breast, and prostate cells to differentiate into mature forms, stop growing, and eventually succumb to programmed cell death. Cancer cells, in contrast, remain immature, rapidly divide, and are immortal.
Says Welsh, "We've shown that if you give [a chemical analog of 1,25-D] to an animal that already has a mammary tumor, that tumor will regress." Other researchers, she notes, have used 1,25-D analogs to inhibit the spread of cancer or the growth of blood vessels that feed new tumors in laboratory animals.
Feldman's group has shown that giving men 1,25-D analogs for 2 years can reduce the buildup in blood of a protein marker of cancer—prostate-specific antigen (PSA). The result suggests that the treatment slowed prostate cancer growth, Feldman says. Several human trials are now testing higher doses of the drugs against prostate cancer and a precancerous condition known as benign prostatic hyperplasia.
Scientists are also investigating whether vitamin D can prevent cancer. Welsh and her colleagues are giving lab animals large doses of vitamin D, rather than 1,25-D or an analog. Whereas 1,25-D is toxic at high does, vitamin D is less so. It's converted to 1,25-D only in specific tissues in response to a signal. The kidneys make most of the 1,25-D and put it into circulation throughout the body. Recently, scientists have discovered that cells of the colon, breast, and prostate can also make this substance for local use. In that case, there's no risk of a toxic systemic effect, such as calcium overload in the blood.
Vitamin D may play a role in the prevention of diabetes as well as of cancer. Many studies have linked vitamin D deficiency to an increased risk of type 2 diabetes, which used to be called adult-onset diabetes. However, says Ken C. Chiu of the University of California, Los Angeles School of Medicine, no one knew what aspect of the disease the vitamin might be acting on. So, his team recently recruited 126 healthy adults and correlated their blood concentrations of vitamin D with their production of and response to insulin.
Both these insulin parameters were low, sometimes falling below the normal range, among people with low blood concentrations of vitamin D, the researchers reported in the May 1 American Journal of Clinical Nutrition.
Vitamin D deficiency "is a double jeopardy for type 2 diabetes," concludes Chiu. He says he now worries that for people on the cusp of developing the disease, vitamin deficiency might tip the balance.
The rub
Today, during much or all of the year, a large share of the U.S. population doesn't even come close to achieving 200 to 600 IU of vitamin D daily. That's the minimum vitamin D intake recommended in 1997 by the National Academies' Food and Nutrition Board, which sets guidelines for vitamins. However, most recent research on vitamin D suggests that many of its health-promoting actions may require far higher doses.
Indeed, Heaney suspects that such high thresholds for vitamin D sufficiency may explain why many of the vitamin's benefits outside bones escaped notice for so long.
Part II: "Vitamin D: What's Enough?"
Many people may need much more
Janet Raloff
This articles reviews how much vitamin D intake one may need.
A few minutes of sun exposure on a summer day can generate huge quantities of vitamin D in a person's body. A cholesterol-like substance in the skin absorbs ultraviolet (UV) energy and creates vitamin D. Then, a cascade of chemical reactions turns vitamin D into a surprisingly versatile hormone—one that has long been recognized to help the body absorb calcium from the diet to build strong bones. Recent work, however, indicates that vitamin D also bolsters muscle strength, insulin action, immune health, and the body's natural defenses against cancer.
UNDEREXPOSED. Sitting in the sun and exposing oneself to the sun at low sun angles little ultraviolet energy is available for making vitamin D.
Inhabitants of the tropics typically have plenty of vitamin D, says Robert P. Heaney of Creighton University in Omaha, Neb. However, studies are now showing that people throughout the industrial world lag far behind. Many in temperate and colder climates don't reach the doses currently recommended to protect bone health, much less the far-higher amounts that research has been linking to additional health-promoting functions.
Some scientists are campaigning for additional vitamin-D enrichment of foods. Others advocate that people spend more time outdoors to increase vitamin D--producing sun exposure. Many hold that the boost must come largely from supplements.
What researchers who study vitamin D do agree on is that many people would benefit from more of the vitamin. At issue is only how much.
Out of the tropics
The Food and Nutrition Board of the National Academies in Washington, D.C., currently recommends that people from infancy through age 50 get 200 international units (IU) of vitamin D per day, that those ages 51 through 70 receive 400 IU daily, and that anyone over 70 get a net of 600 IU from sun, food, and supplements.
That's easy enough to do if you're, say, a white person working outdoors during the summer in New Jersey. In shorts and a T-shirt, such a person can soak up enough ultraviolet rays to produce 12,000 IU of vitamin D within 20 minutes, notes Reinhold Vieth of the University of Toronto.
That production would plummet if the person stayed indoors or slathered on UV-blocking sunscreen or covered up with clothing when out of doors, as recommended for protection against skin cancer.
Global location and skin color also affect the amount of vitamin D a person's skin manufactures. UV intensity falls as one moves from the equator toward Earth's poles, increasing latitude. Evolution compensated by selecting for increasingly unpigmented skin in northern populations, says Boston University endocrinologist Michael F. Holick.
Melanin pigment protects the skin from the damage of UV rays but also lowers the skin's production of vitamin D. In the March American Journal of Clinical Nutrition, Holick quantifies this effect: Fair-skinned people who sunburn easily and rarely tan need just 2 to 10 percent as much sun exposure to produce a unit of vitamin D as do people with the darkest skin.
Season also matters. Holick has found that from the latitude of San Francisco northward—or from Buenos Aires southward—for 3 to 6 months a year, no amount of exposure will generate substantial vitamin D in even the palest skin.
Holick composed a map of North America that shows the minutes of exposure each skin type needs to generate some 1,000 IU of vitamin D without risking sunburn. For instance, a dark-skinned individual living in Anchorage can get that amount in 20 to 30 minutes midday in July, Holick reports in his new book The UV Advantage (2004, with Mark Jenkins, ibooks). A pale person in Honolulu might do it in 1 minute.
Finding sufficiency
Severe vitamin D deficiency softens bones. In children, the result is rickets, characterized by malformed legs. Adults may develop a rare condition called osteomalacia, distinguished by weakened muscles as well as bones. Seventy-five years ago, when the cause of rickets and osteomalacia was first recognized, the remedy was vitamin D--rich cod liver oil. Later, the United States mandated that dairies fortify milk with 100 IU of vitamin D per 8 ounces, and rickets essentially disappeared.
However, rickets has staged a comeback in the U.S. There is no national count, but according to Laurence Grummer-Strawn of the Centers for Disease Control in Atlanta, between 1997 and 1999, "5 per million Georgia children were hospitalized with rickets due to vitamin D deficiency." All were African American, 8 to 21 months old. Numbers could be higher in more-northern locales.
Scientists offer several explanations for rickets' reemergence. Vieth notes that breast-feeding has had a revival and that mother's milk delivers little vitamin D. And Holick points out that doctors have been discouraging parents from letting babies get sun without liberal doses of sunscreen. The Food and Nutrition Board last reviewed its vitamin D recommendations in 1997. As part of that effort, a panel of experts including Vieth, Holick, and Heaney was charged to define how the vitamin should be monitored in people. The active form wasn't deemed suitable because it's manufactured in the body on demand, so it doesn't directly correlate with vitamin D intake and production.
The panel concluded that the best way to evaluate a person's vitamin D status would be to measure concentrations of an inactive form known as 25-hydroxy-vitamin D (25-D) that circulates in the blood.
However, Heaney adds, "we didn't say how much an individual should have—because we didn't know."
In North America, a typical 25-D blood concentration is 40 nanomoles per liter (nmol/l), and scientists long assumed that amount was adequate.
Last year, in a roundtable discussion at an osteoporosis conference in Lausanne, Switzerland, Vieth, Holick, Heaney, and others agreed that an optimal 25-D blood concentration for most people is 75 to 80 nmol/l. Most panelists, therefore, recommended that people strive for 800 to 1,000 IU of Vitamin D daily to achieve it.
That conclusion rests on a variety of experiments. David Hanley of the University of Calgary in Alberta cites studies focusing on parathyroid hormone, one of the factors regulating the natural breakdown of bone that constantly occurs throughout a healthy body. When a person's 25-D concentration dips too low, parathyroid hormone concentration in the blood rises and triggers excessive bone loss. Hanley says that several studies indicate that most people need 75 to 80 nmol/l of 25-D in their blood to protect their bones.
However, people 70 years old and older may need more than 100 nmol/l of 25-D to hold parathyroid hormone at healthy concentrations. Vieth and his colleagues reported this finding, which was based on a study of 1,700 people ages 19 to 97, in the January 2003 Journal of Clinical Endocrinology and Metabolism.
Low 25-D concentrations may identify apparently healthy individuals who are at risk for type 2 diabetes as well as for bone problems. In the May 1 American Journal of Clinical Nutrition, Ken C. Chiu and his colleagues at the University of California, Los Angeles report that the lower the 25-D in study participants, the less likely they were to produce adequate amounts of insulin or to show sufficient sensitivity to insulin. Chiu's team found that increasing a person's blood concentration of 25-D from 25 nmol/l to about 75 nmol/l would "improve insulin sensitivity by 60 percent," which is a greater increase than many antidiabetes drugs provide.
In people over age 60, 25-D blood concentrations correlate with leg strength, according to studies by Bess Dawson-Hughes of the Agriculture Department's Human Nutrition Research Center on Aging in Boston and her colleagues. In one study, they examined data from 4,100 adults representing a cross-section of the U.S. population. People with 25-D concentrations of 40 nmol/l or less walked more slowly and had more trouble rising from a chair than did people with concentrations higher than 86 nmol/l. The results took into account differences between the groups in age, arthritis, weight, and use of a cane, according to the team's report in the Sept. 1 American Journal of Clinical Nutrition.
A third recent study of 25-D links low blood concentrations to colorectal cancer in women. Diane Feskanich of Brigham and Women's Hospital in Boston and her coworkers compared blood tests from 193 cancer patients with those of age-matched women who were cancerfree. All the women were participating in the long-running Nurses' Health Study. In the September Cancer Epidemiology, Biomarkers & Prevention, the researchers report that women in the highest 25-D group—with about 100 nmol/l—had only about half the cancer risk of women in the lowest group, averaging 40 nmol/l.
Silent epidemic
Few people have the blood concentrations of 25-D that researchers recommend. For instance, Hanley described findings from 200 Calgary adults at the Experimental Biology meeting in Washington, D.C., last April. A third of the study's population showed less than 30 nmol/l during at least part of the year. "The average level of 25-D through the four seasons was in the low 60s [nmol/l]," Hanley told Science News. If 80 nmol/l is taken as the cutoff for adequate 25-D, "virtually 100 percent of the population is vitamin D--deficient at least part of the year," he says.
In the March 2003 Nutrition Reviews, Mona Calvo of the U.S. Food and Drug Administration coauthored a review of five studies on vitamin D status in Canada and the United States. They described data indicating a high incidence of vitamin D insufficiency in almost all populations.
In one of those studies, Calvo notes, 42 percent of African American women were 25-D deficient, compared with just 4 percent of their white counterparts. That study defined deficiency as concentrations below 37.5 nmol/l. Calvo says that she prefers to use 80 nmol/l as the minimum adequate blood concentration of 25-D.
The remedy?
Some researchers propose that fortified milk and other foods can cover vitamin D shortfalls. However, the current diet offers, at most, 200 to 400 IU per day. Furthermore, Calvo has new data showing that "African Americans do not consume [vitamin-D] fortified foods." She suspects that many blacks avoid milk, the most highly enriched food, because they have difficulty digesting it.
Harold L. Newmark of Rutgers University in New Brunswick, N.J., and his colleagues propose a new food-enrichment scheme in the Aug. 1 American Journal of Clinical Nutrition. They argue that the best way to help vulnerable groups get enough vitamin D would be to mandate fortification of grain-based products, such as wheat flour, corn meal, and pasta.
Newmark and his colleagues estimate that the cost could be as low as 7 cents per person per year if U.S. foods were fortified to the maximum amount allowed by law (see Should Foods Be Fortified Even More?). They calculate that this would increase vitamin D daily dietary intake by 50 to 200 IU.
Vieth and Holick are among the scientists who advocate increasing "sensible" outdoor activity so people can boost their sun exposure and thus vitamin D supply.
The amount of sun required would pose virtually no increased cancer risk, Holick says. "We evolved in sunlight, and so our whole system is dependent on some exposure to sunlight," he says. In fact, "our health depends on it," he adds.
Most researchers recommend that people get much of their vitamin D intake from supplements and recommend that they boost daily vitamin D intakes to around 1,000 IU.
Holick says that physicians could measure 25-D in blood and prescribe increasing doses of the vitamin until 80 nmol/l is reached. Such personalized prescriptions could take into account lifestyle and pigmentation. For instance, Heaney's research in Omaha indicates that elderly, dark-skinned women could require up to 2,000 IU of vitamin D to keep 25-D concentrations around 80 nmol/l.
Linda D. Meyers, director of the Food and Nutrition Board, which sets the government's recommended daily intake values for all vitamins and some minerals, agrees that "it really is time to look at those [intake standards] again for vitamin D." The standard probably needs to be higher, she acknowledges.
In December, the board will begin discussions with nutrition experts on which nutrients need to be reevaluated. Considering the wealth of data that has been coming out, "I'm thinking vitamin D might even offer a case study to help us," says Meyers.
"[Vitamin D] deserves to be in the first group reexamined," she told Science News. "It really is time to look at that one again."
REFERENCES for part 2 Article
Aeschbach, D., et al. 2003. A longer biological night in long sleepers than in short sleepers. Journal of Clinical Endocrinology & Metabolism 88(January):26-30. Available at http://intl-jcem.endojournals.org/cgi/content/full/88/1/26.
Bischoff-Ferrari, H.A. . . . B. Dawson-Hughes, et al. 2004. Effect of vitamin D on falls: A meta-analysis. Journal of the American Medical Association 291(April 28):1999-2006. Abstract available at http://jama.ama-assn.org/cgi/content/abstract/291/16/1999.
Calvo, M.S., and S.J. Whiting. 2004. Vitamin D insufficiency: A significant risk factor in chronic diseases and potential disease-specific biomarkers of vitamin D sufficiency. Experimental Biology meeting. April 17-21. Washington, DC.
______. 2003. Prevalence of vitamin D insufficiency in Canada and the United States: Importance to health status and efficacy of current food fortification and dietary supplement use. Nutrition Reviews 61(March):107-113. Abstract available at http://dx.doi.org/10.1301/nr.2003.marr.107-113.
Chiu, K.C., et al. 2004. Hypovitaminosis D is associated with insulin resistance and b cell dysfunction. American Journal of Clinical Nutrition 79(May 1):820-825. Abstract available at http://www.ajcn.org/cgi/content/abstract/79/5/820.
Dawson-Hughes, B., et al. 2003. Vitamin D, how much is enough and why. 5th International Symposium on Nutritional Aspects of Osteoporosis. May 14-17. Lausanne.
DeLucia, M.C., M.E. Mitnick, and T.O. Carpenter. 2003. Nutritional rickets with normal circulating 25-hydroxyvitamin D: A call for reexamining the role of dietary calcium intake in North American infants. Journal of Clinical Endocrinology & Metabolism 88(August):3539-3545. Available at http://jcem.endojournals.org/cgi/content/full/88/8/3539.
Feskanich, D., et al. 2004. Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiology, Biomarkers & Prevention 13(September):1502-1508. Abstract available at http://cebp.aacrjournals.org/cgi/content/abstract/13/9/1502.
Holick, M.F. 2004. Vitamin D: Importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. American Journal of Clinical Nutrition 79(March):362-371. Available at http://www.ajcn.org/cgi/content/full/79/3/362.
Institute of Medicine and National Research Council. 1997. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, D.C.: National Academy Press. Available at http://www.nap.edu/books/0309063507/html/.
Nesby-O'Dell, S., et al. 2002. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey, 1988--1994. American Journal of Clinical Nutrition 76(July 1):187-192. Available at http://www.ajcn.org/cgi/content/full/76/1/187.
Newmark, H.L., R.P. Heaney, and P.A. Lachance. 2004. Should calcium and vitamin D be added to the current enrichment program for cereal-grain products? American Journal of Clinical Nutrition 80(August):264-270. Available at http://www.ajcn.org/cgi/content/full/80/2/264.
Rivkees, S.A. 2003. Time to wake-up to the individual variation in sleep needs. Journal of Clinical Endocrinology & Metabolism 88(January):24-25. Available at http://intl-jcem.endojournals.org/cgi/content/full/88/1/24.
Rucker, D. . . . and D.A. Hanley. 2002. Vitamin D insufficiency in a population of healthy western Canadians. Canadian Medical Association Journal 166(June 11):1517-1524. Available at http://www.cmaj.ca/cgi/content/full/166/12/1517.
Vieth, R., Y. Ladak, and P.G. Walfish. 2003. Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. Journal of Clinical Endocrinology & Metabolism 88(January):185-191. Available at http://intl-jcem.endojournals.org/cgi/content/full/88/1/185.
Further Readings:
Barger-Lux, M., and R.P. Heaney. 2002. Effects of above average summer sum exposure on serum 25-hydroxyvitamin D and calcium absorption. Journal of Clinical Endocrinology & Metabolism 87(November):4952-4956. Available at http://jcem.endojournals.org/cgi/content/full/87/11/4952.
Feskanich, D., W.C. Willett, and G.A. Colditz. 2003. Calcium, vitamin D, milk consumption, and hip fractures: A prospective study among postmenopausal women. American Journal of Clinical Nutrition 77(February):504-511. Available at http://www.ajcn.org/cgi/content/full/77/2/504.
Heaney, R.P. 2003. Vitamin D, nutritional deficiency, and the medical paradigm. Journal of Clinical Endocrinology & Metabolism 88(November):5107-5108.
Holick, M.F., et al. 1992. The vitamin D content of fortified milk and infant formula. New England Journal of Medicine 326(April 30):1178-1181. Abstract available at http://content.nejm.org/cgi/content/abstract/326/18/1178.
Hollis, B.W. 2004. The determination of circulating 25-hydroxyvitamin D: No easy task. Journal of Clinical Endocrinology & Metabolism 88(July):3149-3151.
Lane, N.E., et al. 1999. Serum vitamin D levels and incident changes of radiographic hip osteoarthritis. Arthritis & Rheumatism 42(May):854-860. Abstract available at http://www3.interscience.wiley.com/cgi-bin/abstract/78502195/ABSTRACT.
Munger, K.L., et al. 2004. Vitamin D intake and incidence of multiple sclerosis. Neurology 62(Jan. 13):60-65. Abstract available at http://www.neurology.org/cgi/content/abstract/62/1/60.
Raloff, J. 2004. Vitamin boost. Science News 166(Oct.9):232-233. Available at http://www.sciencenews.org/articles/20041009/bob8.asp.
______. 2004. Should foods be fortified even more? Science News Online (Sept. 11). Available at http://www.sciencenews.org/articles/20040911/food.asp.
Vieth, R., and D. Fraser. 2002. Vitamin D insufficiency: No recommended dietary allowance exists for this nutrient. Canadian Medical Association Journal 166(June 11):1541-1542. Available at http://www.cmaj.ca/cgi/content/full/166/12/1541.
Vieth, R., P.-C.R. Chan, and G.D. MacFarlane. 2001. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. American Journal of Clinical Nutrition 73(February):288-294. Available at http://www.ajcn.org/cgi/content/full/73/2/288.
Bischoff-Ferrari, H.A., T. Dietrich, et al. 2004. Higher 25-hydroxyvitamin D concentrations are asociated with better lower-extremity function in both active and inactive persons aged more than 60 y. American Journal of Clinical Nutrition 80(September):752-758. Abstract available at http://www.ajcn.org/cgi/content/abstract/80/3/752.
Bischoff-Ferrari, H.A., et al. 2004. Effect of vitamin D on falls: A meta-analysis. Journal of the American Medical Association 291(April 28):1999-2006. Abstract available at http://jama.ama-assn.org/cgi/content/abstract/291/16/1999.
Bischoff-Ferrari, H.A., et al. 2004. Vitamin D receptor expression in human muscle tissue decreases with age. Journal of Bone and Mineral Research 19(February):265-269. Abstract available at http://www.jbmr-online.org/abstracts/01902/JBMR0190202650_abs.html.
Bischoff, H.A., et al. 2003. Effects of vitamin D and calcium supplementation on falls: A randomized controlled trial. Journal of Bone and Mineral Research 18(February):343-351. Available at http://www.jbmr-online.org/fulltext/01802/03430/JBMR0180203430.html?free.
Cantorna, M.T., et al. 2000. 1,25-dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. Journal of Nutrition 130(November):2648-2652. Available at http://www.nutrition.org/cgi/content/full/130/11/2648.
Cantorna, M.T., C.E. Hayes, and H.F. DeLuca. 1998. 1,25-dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. Journal of Nutrition 128(January):68-72. Available at http://www.nutrition.org/cgi/content/full/128/1/68.
Cantorna, M.T., C.E. Hayes, and H.F. DeLuca. 1996. 1,25-dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proceedings of the National Academy of Sciences 93(July 23):7861-7864. Available at http://www.pnas.org/cgi/content/abstract/93/15/7861.
Chiu, K.C., et al. 2004. Hypovitaminosis D is associated with insulin resistance and b cell dysfunction. American Journal of Clinical Nutrition 79(May 1):820-825. Abstract available at http://www.ajcn.org/cgi/content/abstract/79/5/820.
Dietrich, T. . . . and H.A. Bischoff-Ferrari. 2004. Association between serum concentrations of 25-hydroxyvitamin D3 and periodontal disease in the US population. American Journal of Clinical Nutrition 80(July 1):108-113. Abstract available at http://www.ajcn.org/cgi/content/abstract/80/1/108.
Feldman, D., J.W. Pike, and F.H. Glorieux, eds. In press. Vitamin D, 2nd ed. Academic Press.
Heaney, R.P. 1999. Lessons for nutritional science from vitamin D. American Journal of Clinical Nutrition 69(May 1):825-826. Available at http://www.ajcn.org/cgi/content/full/69/5/825.
Institute of Medicine and National Research Council. 1997. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, D.C.: National Academy Press. Available at http://www.nap.edu/books/0309063507/html/.
Munger, K.L., et al. 2004. Vitamin D intake and incidence of multiple sclerosis. Neurology 62(Jan. 13):60-65. Abstract available at http://www.neurology.org/cgi/content/abstract/62/1/60.
Nesby-O'Dell, S., et al. 2002. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey, 1988--1994. American Journal of Clinical Nutrition 76(July 1):187-192. Available at http://www.ajcn.org/cgi/content/full/76/1/187.
Peehl, D.M., A.V. Krishnan, and D. Feldman. 2003. Pathways mediating the growth-inhibitory actions of vitamin D in prostate cancer. Journal of Nutrition 133(July):2461S-2469S. Available at http://www.nutrition.org/cgi/content/full/133/7/2461S.
Welsh, J., et al. 2003. Vitamin D-3 receptor as a target for breast cancer prevention. Journal of Nutrition 133(July):2425S-2433S. Available at http://www.nutrition.org/cgi/content/full/133/7/2425S.
Further Readings:
Bischoff-Ferrari, H.A., T. Dietrich, et al. 2004. Positive association between 25-hydroxy vitamin D levels and bone mineral density: A population-based study of younger and older adults. American Journal of Medicine 116(May 1):634-639. Abstract available at http://dx.doi.org/10.1016/j.amjmed.2003.12.029.
Cantorna, M.T. 2000. Vitamin D and autoimmunity: Is vitamin D status an environmental factor affecting autoimmune disease prevalence? Proceedings of the Society for Experimental Biology & Medicine 223(March):230-233. Available at http://www.ebmonline.org/cgi/content/full/223/3/230.
Lane, N.E., et al. 1999. Serum vitamin D levels and incident changes of radiographic hip osteoarthritis. Arthritis & Rheumatism 42(May):854-860. Abstract available at http://www3.interscience.wiley.com/cgi-bin/abstract/78502195/ABSTRACT.
Newmark, H.L., and N. Suh. 2004. Mechanistic hypothesis for the interaction of dietary fat, calcium, and vitamin D in breast cancer. Medical Hypotheses and Research 1(July):67-75.
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