Vitamin D and inflammation

December 15, 2005

http://www.sciencenews.org/articles/20041009/bob8.asp

Vitamin Boost From muscle strength to immunity, scientists find new vitamin

D benefits Janet Raloff

First in a two-part series. Part II: " Vitamin D: What's Enough? " is available

at http://www.sciencenews.org/articles/20041016/bob9.asp. 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. COVERED. Outdoor

activities—even reading—build vitamin D in people as long as enough of a

person's skin is exposed to the sun.

PhotoDisk

What's now clear is that vitamin D is a potent force in regulating cell

growth, immunity, and energy metabolism, observes 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 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, 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? " is available at http://www.sciencenews.org/articles/20041016/bob9.asp.

---------------------------------

Letters:

I found both your articles on vitamin D very interesting. My question now is

whether the rays received in a tanning bed can cause the skin to manufacture

vitamin D. Wade

Kalamazoo, Mich.

Ultraviolet–B radiation triggers the skin to produce vitamin D, whether those

rays come from the sun or a lamp. However, not all tanning salons use lamps that

emit UV-B rays as well as UV-A wavelengths.—J. Raloff

Two thoughts on vitamin D: Are treatments for seasonal affective mood

disorders, involving shining bright lights on the skin, effective simply because

they stimulate the production of vitamin D? Does exposure to sunlight affect

blood-cholesterol levels? Steve Palmer

Plainfield, N.J.

Could the lack of vitamin D be a cause of the " death in the dark months " of

elderly people? The rise of depression in the winter months could be accounted

for, as well, and perhaps treated very simply by adding the vitamin to our

diets. Follow up, please. Karl L. Roesch

Arlee, Mont.

---------------------------------

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References:

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. , 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. , 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.

Raloff, J. 2004. Vitamin D: What's enough? Science News 166(Oct. 16):248-249.

Available at http://www.sciencenews.org/articles/20041016/bob9.asp.

______. 2004. Should foods be fortified even more? Science News Online (Sept.

18). Available at http://www.sciencenews.org/articles/20040918/food.asp.

______. 2001. Sometimes an antibiotic is much more. Science News 159(Feb.

24):116. Available to subscribers at

http://www.sciencenews.org/articles/20010224/fob2.asp.

______. 1996. Vanishing flesh. Science News 150(Aug. 10):90-91. Available at

http://www.sciencenews.org/pages/sn_arch/8_10_96/bob1.htm.

Sources:

Heike A. Bischoff-Ferrari

Harvard Medical School

Brigham and Women's Hospital

Division of Aging

1620 Tremont Street

Boston, MA 02120

Margherita T. Cantorna

Penn State University

Health and Human Development Nutritional Sciences

118A South Building

University Park, PA 16802

Dietrich

Department of Health Policy and Health Services Research

Goldman School of Dental Medicine

Boston University

715 Albany Street

Boston, MA 02118

Feldman

Stanford University

300 Pasteur Drive

Endocrinology Division, MC 5103

Stanford, CA 94305-5103

P. Heaney

Creighton University Medical Center

601 North 30th Street

Suite 4841

Omaha, NE 68131

D. Meyers

Food and Nutrition Board

Institute of Medicine

National Academies

500 Fifth Street, NW

Washington, DC 20010

Kassandra Munger

Department of Nutrition

Harvard School of Public Health

665 Huntington Avenue

Boston, MA 02115

JoEllen Welsh

Department of Biological Sciences

University of Notre Dame

Notre Dame, IN 46556

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December 15, 2005

One of my docs put me on this because I was low & said it was really important

for a number of things! Vit D. Loni

Kathy <kathywnb@...> wrote: