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I find the references to mitigating sarcopenia of particular interest

in this Science News article.

Thanks,

Doug

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

Science News Online

Week of Oct. 9, 2004; Vol. 166, No. 15

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.

[iMAGE] COVERED. Outdoor activities & #151;even reading & #151;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 & #168;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 & #168;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 & #151;in which a

person's immune system attacks parts of his or her own body & #151;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 & #151;though not skin

cancer & #151;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 & #151;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.

If you have a comment on this article that you would like considered

for publication in Science News, send it to editors@....

Please include your name and location.

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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?fr

ee.

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 & #150;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

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

From Science News, Vol. 166, No. 15, Oct. 9, 2004, p. 232.

Copyright © 2004 Science Service. All rights reserved.

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