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Vitamin D upregulates a gene called GDF-15, which suppresses inflammation and appears to protect against prostate cancer. Vitamin D3 is a an anti-cancer powerhouse. Most of us do not get enough sunshine, make sure you are taking vitamin D3!

A University of Colorado Cancer Center study recently published in the journal Prostate offers compelling evidence that inflammation may be the link between Vitamin D and prostate cancer. Specifically, the study shows that the gene GDF-15, known to be upregulated by Vitamin D, is notably absent in samples of human prostate cancer driven by inflammation.

“When you take Vitamin D and put it on prostate cancer cells, it inhibits their growth. But it hasn’t been proven as an anti-cancer agent. We wanted to understand what genes Vitamin D is turning on or off in prostate cancer to offer new targets,” says James R. Lambert, PhD, investigator at the CU Cancer Center and associate research professor in the CU School of Medicine Department of Pathology.

Since demonstrating that Vitamin D upregulates the expression of GDF-15, Lambert and colleagues, including Scott Lucia, MD, wondered if this gene might be a mechanism through which Vitamin D works in prostate cancer. Initially it seemed as if the answer was no.

“We thought there might be high levels of GDF-15 in normal tissue and low levels in prostate cancer, but we found that in a large cohort of human prostate tissue samples, expression of GDF-15 did not track with either normal or cancerous prostate tissue,” Lambert says.

But then the team noticed an interesting pattern: GDF-15 was uniformly low in samples of prostate tissue that contained inflammation.

“Inflammation is thought to drive many cancers including prostate, gastric and colon. Therefore, GDF-15 may be a good thing in keeping prostate tissue healthy – it suppresses inflammation, which is a bad actor potentially driving prostate cancer,” Lambert says.

The study used a sophisticated computer algorithm to analyze immunohistochemical (IHC) data, a task that in previous studies had been done somewhat subjectively by pathologists. With this new technique, Lambert, Lucia and colleagues were able to quantify the expression of the GDF-15 protein and inflammatory cells by IHC staining on slides taken from these human prostate samples.

Additionally encouraging is that the gene GDF-15 was shown to suppress inflammation by inhibiting another target, NFkB. This target, NFkB, has been the focus of many previous studies in which it has been shown to promote inflammation and contribute to tumor formation and growth; however, researchers have previously been unable to drug NFkB to decrease its tumor-promoting behavior.

“There’s been a lot of work on inhibiting NFkB,” says Lambert. “Now from this starting point of Vitamin D in prostate cancer, we’ve come a long way toward understanding how we might use GDF-15 to target NFkB, which may have implications in cancer types far beyond prostate.”

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What Do You Lack? Probably Vitamin D
By JANE E. BRODY
Published: July 26, 2010

Vitamin D promises to be the most talked-about and written-about supplement of the decade. While studies continue to refine optimal blood levels and recommended dietary amounts, the fact remains that a huge part of the population — from robust newborns to the frail elderly, and many others in between — are deficient in this essential nutrient.

If the findings of existing clinical trials hold up in future research, the potential consequences of this deficiency are likely to go far beyond inadequate bone development and excessive bone loss that can result in falls and fractures. Every tissue in the body, including the brain, heart, muscles and immune system, has receptors for vitamin D, meaning that this nutrient is needed at proper levels for these tissues to function well.

Studies indicate that the effects of a vitamin D deficiency include an elevated risk of developing (and dying from) cancers of the colon, breast and prostate; high blood pressure and cardiovascular disease; osteoarthritis; and immune-system abnormalities that can result in infections and autoimmune disorders like multiple sclerosis, Type 1 diabetes and rheumatoid arthritis.

Most people in the modern world have lifestyles that prevent them from acquiring the levels of vitamin D that evolution intended us to have. The sun’s ultraviolet-B rays absorbed through the skin are the body’s main source of this nutrient. Early humans evolved near the equator, where sun exposure is intense year round, and minimally clothed people spent most of the day outdoors.

“As a species, we do not get as much sun exposure as we used to, and dietary sources of vitamin D are minimal,” Dr. Edward Giovannucci, nutrition researcher at the Harvard School of Public Health, wrote in The Archives of Internal Medicine. Previtamin D forms in sun-exposed skin, and 10 to 15 percent of the previtamin is immediately converted to vitamin D, the form found in supplements. Vitamin D, in turn, is changed in the liver to 25-hydroxyvitamin D, the main circulating form. Finally, the kidneys convert 25-hydroxyvitamin D into the nutrient’s biologically active form, 1,25-dihydroxyvitamin D, also known as vitamin D hormone.

A person’s vitamin D level is measured in the blood as 25-hydroxyvitamin D, considered the best indicator of sufficiency. A recent study showed that maximum bone density is achieved when the blood serum level of 25-hydroxyvitamin D reaches 40 nanograms per milliliter or more.

“Throughout most of human evolution,” Dr. Giovannucci wrote, “when the vitamin D system was developing, the ‘natural’ level of 25-hydroxyvitamin D was probably around 50 nanograms per milliliter or higher. In modern societies, few people attain such high levels.”

A Common Deficiency

Although more foods today are supplemented with vitamin D, experts say it is rarely possible to consume adequate amounts through foods. The main dietary sources are wild-caught oily fish (salmon, mackerel, bluefish, and canned tuna) and fortified milk and baby formula, cereal and orange juice.

People in colder regions form their year’s supply of natural vitamin D in summer, when ultraviolet-B rays are most direct. But the less sun exposure, the darker a person’s skin and the more sunscreen used, the less previtamin D is formed and the lower the serum levels of the vitamin. People who are sun-phobic, babies who are exclusively breast-fed, the elderly and those living in nursing homes are particularly at risk of a serious vitamin D deficiency.

Dr. Michael Holick of Boston University, a leading expert on vitamin D and author of “The Vitamin D Solution” (Hudson Street Press, 2010), said in an interview, “We want everyone to be above 30 nanograms per milliliter, but currently in the United States, Caucasians average 18 to 22 nanograms and African-Americans average 13 to 15 nanograms.” African-American women are 10 times as likely to have levels at or below 15 nanograms as white women, the third National Health and Nutrition Examination Survey found.

Such low levels could account for the high incidence of several chronic diseases in this country, Dr. Holick maintains. For example, he said, in the Northeast, where sun exposure is reduced and vitamin D levels consequently are lower, cancer rates are higher than in the South. Likewise, rates of high blood pressure, heart disease, and prostate cancer are higher among dark-skinned Americans than among whites.

The rising incidence of Type 1 diabetes may be due, in part, to the current practice of protecting the young from sun exposure. When newborn infants in Finland were given 2,000 international units a day, Type 1 diabetes fell by 88 percent, Dr. Holick said.

The current recommended intake of vitamin D, established by the Institute of Medicine, is 200 I.U. a day from birth to age 50 (including pregnant women); 400 for adults aged 50 to 70; and 600 for those older than 70. While a revision upward of these amounts is in the works, most experts expect it will err on the low side. Dr. Holick, among others, recommends a daily supplement of 1,000 to 2,000 units for all sun-deprived individuals, pregnant and lactating women, and adults older than 50. The American Academy of Pediatrics recommends that breast-fed infants receive a daily supplement of 400 units until they are weaned and consuming a quart or more each day of fortified milk or formula.

Given appropriate sun exposure in summer, it is possible to meet the body’s yearlong need for vitamin D. But so many factors influence the rate of vitamin D formation in skin that it is difficult to establish a universal public health recommendation. Asked for a general recommendation, Dr. Holick suggests going outside in summer unprotected by sunscreen (except for the face, which should always be protected) wearing minimal clothing from 10 a.m. to 3 p.m. two or three times a week for 5 to 10 minutes.

Slathering skin with sunscreen with an SPF of 30 will reduce exposure to ultraviolet-B rays by 95 to 98 percent. But if you make enough vitamin D in your skin in summer, it can meet the body’s needs for the rest of the year, Dr. Holick said.

Can You Get Too Much?

If acquired naturally through skin, the body’s supply of vitamin D has a built-in cutoff. When enough is made, further exposure to sunlight will destroy any excess. Not so when the source is an ingested supplement, which goes directly to the liver.

Symptoms of vitamin D toxicity include nausea, vomiting, poor appetite, constipation, weakness and weight loss, as well as dangerous amounts of calcium that can result in kidney stones, confusion and abnormal heart rhythms.

But both Dr. Giovannucci and Dr. Holick say it is very hard to reach such toxic levels. Healthy adults have taken 10,000 I.U. a day for six months or longer with no adverse effects. People with a serious vitamin D deficiency are often prescribed weekly doses of 50,000 units until the problem is corrected. To minimize the risk of any long-term toxicity, these experts recommend that adults take a daily supplement of 1,000 to 2,000 units.

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