The vitamin D miracle: Is it for real?

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The vitamin D miracle: Is it for real?

The claims have been sensational. Mittelstaedt checks up on the research

behind the hype

MARTIN MITTELSTAEDT

From Saturday's Globe and Mail

March 8, 2008 at 9:32 AM EDT

In the summer of 1974, brothers and Cedric Garland had a heretical

brainwave.

The young epidemiologists were watching a presentation on death rates from

cancer county by county across the United States. As they sat in a lecture hall

at s Hopkins University in Baltimore looking at the colour-coded cancer

maps, they noticed a striking pattern, with the map for colon cancer the most

pronounced.

Counties with high death rates were red; those with low rates were blue. Oddly,

the nation was almost neatly divided in half, red in the north and blue in the

south. Why, they wondered, was the risk of dying from cancer greater in bucolic

Maine than in highly polluted Southern California?

The two had arrived at s Hopkins a few days earlier, having driven their

Mustang from their hometown of San Diego. was about to begin graduate

studies and Cedric his first job as a professor. It was July, and the trip

through the sunny South gave them an idea as they studied the cancer maps:

Exposure to sunshine varies dramatically depending on the latitude. What if

that's what was behind the varying cancer rates?

Their hypothesis, painstakingly developed and published six years later in the

International Journal of Epidemiology, was that sunlight has a powerful

anti-cancer effect through its role in producing vitamin D in bare skin. Those

living at northern latitudes, they theorized, receive less sunlight and make

less of the vitamin, which in turn increases their risk of dying from cancer.

Today, with vitamin D so much in the news, it's hard to believe that it took

decades for the Garlands' hypothesis to gain traction in the mainstream medical

community.

But the benefits of vitamin D are no longer restricted to cancer prevention:

Studies have linked a shortage of the compound to such serious, chronic ailments

as multiple sclerosis, diabetes, heart disease, influenza and schizophrenia.

Cedric Garland, now a professor of preventive medicine at the University of

California, San Diego, is so convinced of this broad link that he says, " I think

vitamin D is introducing a golden age in medicine. "

And he's not alone. So compelling is the latest research that a number of

credible medical researchers and public-health advocates, many of them in

Canada, have started taking doses far above 200 to 600 international units - the

daily intake recommended by Health Canada, depending on age with an upper limit

of 2,000 IU.

Canada's leading vitamin D researcher, the University of Toronto's Reinhold

Vieth, says he has been knocking back 8,000 units a day - four times the maximum

- for years.

Should everyone be doing the same?

Dr. Vieth says he believes that what he's doing is completely safe - after all,

his intake is similar to the amount of vitamin D a sunbathing Canadian might

make naturally on a summer day.

And Heaney, a medical researcher at Creighton University in Omaha, says

his Canadian colleague is hardly alone in his super-sized approach. " All the

vitamin D researchers, to a person, I've not found an exception, are convinced

enough by the data to walk the walk, " says Dr. Heaney, who last year helped to

conduct a study, reported in the American Journal of Clinical Nutrition, that

linked vitamin D supplements to an astonishing 60-per-cent decrease in cancer

incidence among middle-aged and older women.

Cedric Garland argues that, rather than pollutants or some other cause,

insufficient levels of vitamin D are at the root of the Western world's cancer

epidemic. What's more, if more people took supplements, the population of

northern regions would be a lot healthier all round.

" We will be preventing an extremely broad range of diseases in a single,

inexpensive way with virtually no complications, " he explains. " It will affect

every branch of medicine and public health favourably. "

TOO GOOD TO BE TRUE?

It seems almost inconceivable that geography could damn someone to a

life-threatening illness - that the mere fact of living in a northern country

such as Canada could be a health hazard.

The Garland brothers' hypothesis also defies the long-held conventional view

that cancer is caused mainly by bad lifestyle habits, bad genes or carcinogens.

Indeed, it suggests that some types of cancer could be better described as

nutritional-deficiency diseases, much like scurvy or rickets.

Consequently, many experts have been skeptical, aware that much-touted nutrients

in the past have often failed to live up to their initial hype.

" The problem with vitamins has been that generally the evidence, for whatever

reason, doesn't pan out, " cautions Len Lichtenfeld, deputy chief medical officer

of the American Cancer Society.

Dr. Lichtenfeld says medical authorities have been burned so often over

supplements that he would like to see a " substantial amount " of additional

research before he is convinced that vitamin D is the real thing.

The idea that sunlight has beneficial health effects also flies in the face of

advice to avoid sun exposure to reduce the risk of skin cancer.

Nevertheless, the idea that vitamin D insufficiency plays a role in cancer and

other chronic adult diseases continues to gain scientific credence as a

plausible theory, earned new respect for the long-underappreciated vitamin.

Though it first drew attention in the 1920s as a cure for rickets (bone health,

not cancer, is why Health Canada even has a recommended intake), it has largely

been treated like Rodney Dangerfield ever since. In our health-conscious age, it

has been overshadowed by supplements such as vitamin C and beta carotene.

But since the Garland brothers kicked off interest in vitamin D with their data

on colon cancer, other studies have shown that more than a dozen other cancers,

including the big killers, breast and prostate, as well as an array of other

diseases appear sensitive to insufficiencies of the vitamin.

The idea behind the research is simple: Humans evolved in a sunlight-filled

environment near the equator, and still have countless biological processes

exquisitely calibrated to the rich vitamin D levels we would have if we were

still basking under the hot sun year-round.

But by migrating to higher latitudes, where strong sunlight is not present

during the fall and winter, most humans upset their vitamin D metabolism,

creating susceptibilities to chronic ailments that research is now linking to

insufficiencies.

The question for Canadians is: If we're so short of a crucial vitamin, shouldn't

we be compensating? And if we did, would vitamin D be a proverbial magic pill,

capable of curing much of what ails us?

Although the guidelines jointly issued by the U.S. and Canadian governments say

adults need only 200 to 600 IU of vitamin D daily, depending on age, the women

in Dr. Heaney's study took 1,100 IU daily, while he himself takes 1,500 IU

daily.

(Although the international units nomenclature makes the numbers seem large, the

actual weight represented by a single IU of vitamin D is dust-like, at less than

a millionth of a gram. The vitamin, by acting like a hormone in the body's

cells, packs a big biological punch in minute amounts.)

Radical conservatives

The Canadian Cancer Society is one of the more conservative health-advocacy

agencies, but last year became the first major organization in the world to

embrace the idea of large-scale, population-wide vitamin D supplementation to

combat cancer. It started recommending that white adults take up to 1,000 IU

daily in fall and winter, and non-whites, because of their higher susceptibility

to vitamin D insufficiency at northern latitudes, take that amount year-round.

(Canada doesn't keep national illness statistics by race, so the degree to which

non-whites are being affected by ailments linked to low vitamin D levels isn't

known.)

The Canadian Pediatric Society followed suit shortly after, calling for pregnant

and breastfeeding women to take 2,000 IU daily, with a goal of preventing

childhood diseases.

The Canadian Cancer Society's decision came after years of monitoring the

research. Vitamin D " kept coming up. It kept hitting the bar that reaches your

attention, " says Logan, the society's director of cancer-control policy.

" It wasn't one study and that was the end of the story. There were multiple

research studies continued to be published in peer-reviewed journals. "

One study, in the journal Circulation, found that those with low vitamin D

status had a 62-per-cent increased risk of heart failure. Another, published in

Archives of Internal Medicine, found that those who take vitamin D supplements

cut mortality risk by 7 per cent. A third report, by scientists at the U.S.

National Cancer Institute, found that, while vitamin D didn't affect overall

cancer-death risk, those with relatively high levels of it in their blood had a

72-per-cent lower risk of dying from colorectal cancer.

Other studies have found that low blood levels are an excellent predictor of who

goes on to develop cancer and heart disease and that people diagnosed with

cancer during the vitamin D-rich summer have a better prognosis than those

diagnosed during winter.

Not everyone is convinced, however. Critics charge that most of the findings -

such as the Garlands' cancer maps - constitute only circumstantial evidence. And

when the Canadian Cancer Society asked the American Cancer Society to join them

in recommending more vitamin D, it refused.

" I think it's fair to say we had discussions and we agreed to disagree on that.

Our position is that we really want what I call solid evidence .... that there

in fact is a reduction in cancer mortality without a significant increase in

risk with vitamin D supplementation, " Dr. Lichtenfeld says. He wants to see

drug-style clinical trials to validate the benefits and assess the risks, he

says, before telling 330 million Americans to start taking supplements.

Similarly, McLaughlin, vice-president of preventive oncology for Cancer

Care Ontario, says the research on vitamin D is too thin at this point to

recommend taking higher doses to prevent cancer. He dismisses Dr. Heaney's study

as " largely uninformative " because of its small size (about 450 women) and

because the subjects also took calcium supplements, which may have affected the

results.

But even though Ms. Logan says the Canadian Cancer Society agrees that all the

science on vitamin D may not be in yet, evidence to date strongly suggests that

not acting on the implications of the research is risky. Cancers affected

include such big killers as breast, prostate and colon, which will claim more

than 10,000 Canadians this year.

" You don't need to wait for every scientific question to be answered before you

take action, " Ms. Logan says. " Where there is evidence of harm, even in the face

of scientific uncertainty, you should so something about it. "

Mittelstaedt is The Globe and Mail's environment reporter.

JUST D FACTS

Vitamin D is measured by levels in blood. Many Canadians have 40 nanomoles/litre

or less, particularly in winter. Many researchers believe levels need to be at

least twice that high to reduce chronic disease risk.

Vitamin D is produced when exposed skin has a photochemical reaction to

ultraviolet light rays from the sun. Nearly all the vitamin D circulating in our

bodies is made this way, with a typical white-skinned person in a bathing suit

under a noonday summer sun in Canada producing about 10,000 international units

in 15 to 20 minutes. Non-whites need about five times longer to make the same

amount, because the melanin in their skin acts as a sunscreen against UVB rays.

During the fall and winter, sunlight at Canadian latitudes is too weak to cause

any vitamin D production.

Vitamin D synthesis in skin occurs only when the UV index is three or higher,

roughly the period around noon from March to October in southern parts of the

country. A rule of thumb is that if your shadow is longer than you are, the

sunlight is not intense enough.

Some of the very few foods that contain vitamin D are: cod liver oil (1,300 IU

per tablespoon); wild salmon (1,000 IU per serving); farmed salmon (250 IU);

sardines (600 IU); fortified milk or orange juice (100 IU); egg yolk (25 IU);

fresh shiitake mushrooms and some organ meats (traces in both). Most

multivitamins contain 400 IU. Over-the-counter pills and drops contain up to

1,000 IU.

Health Canada's daily intake recommendations, based primarily on a 1997 study,

are: newborns to 12 months, 400 IU; age 1 to 50, 200 IU; 51 to 70, 400 IU; over

70, 600 IU; with an overall upper limit of 2,000 IU.

Many vitamin D advocates say Health Canada is too conservative. The Canadian

Cancer Society, for example, recommends that non-white adults take 1,000 IU

daily year-round and whites take that amount in fall and winter. The Canadian

Pediatric Society recommends 2,000 IU daily for pregnant and breastfeeding

women.

Toxicity has occurred after long-term exposure to massive amounts, ranging from

50,000 IU to 150,000 IU daily. Effects such as bone demineralization may occur

with chronic daily doses exceeding 10,000 IU. No illnesses have been reported

for doses under 3,800 IU daily.

A U.S. study in 2007 found that overall risk of cancer in women was cut by 60

per cent when they were given 1,100 IU of vitamin D per day, plus a calcium

supplement.

Another study estimated the dose to cut colon-cancer risk in half: 1,000 IU

daily. The amount estimated to cut breast-cancer risk in half: 4,000 IU daily.

Researchers say women could stay within Health Canada guidelines and still reach

4,000 IU daily by getting 2,000 IU from diet and supplements and the rest from

modest sun exposure.

There is some evidence that girls can cut their future risk of breast cancer by

taking high levels of vitamin D during their teens.

U.S. researchers estimate that vitamin D insufficiency causes up to 60,000

premature cancer deaths a year in the country, or nearly 10 per cent of total

mortality from the disease. If the same percentage applies to Canada, low

vitamin D status leads to about 7,000 premature cancer deaths here annually.

While there is a risk of skin cancer from overexposure to ultraviolet light,

researchers say, the benefits of modest sun exposure in preventing serious,

hard-to-treat cancers outweighs that risk. Furthermore, they say, skin cancer is

relatively easy to treat.

A 2001 Finnish study found that children given 2,000 IU daily cut their risk of

getting juvenile diabetes by 80 per cent.

The strong correlation between latitude and the incidence of multiple sclerosis

has led researchers to suspect the trend is related to vitamin D status. In the

U.S., for example, MS rates are four times higher in northern states, along the

Canadian border, than in the southern parts of the country. Similarly,

Australian research shows the incidence of MS increases the farther people live

from the equator. The highest incidence rates in the world are found in Northern

Europe and Canada.

Mittelstaedt

GENE GENIE

New insights into how the 'magic pill' works

The role of vitamin D in carcinomas could explain one of the biggest mysteries

about the cause of cancer: why so many people who develop the disease have no

known risk factors, such as a family history of the illness.

The simple answer may be that Vitamin D interacts with an unusually large number

of our genes, working like a master switch to turn them on or off. Researchers

believe a deficiency of the vitamin leads to a deficiency of the proteins

manufactured under the direction of these genes, which then undermines key

defences against seemingly unrelated diseases such as cancer, diabetes and

multiple sclerosis.

White, who has been studying the antimicrobial activities of vitamin D at

McGill University in Montreal, says that " virtually every cell " in the human

body has receptors for vitamin D and that hundreds of different genes may be

regulated by it.

Vitamin D's most profound gene-influenced activity appears to be in keeping

healthy the broad category of cells known as epithelium, which line the outsides

of our organs and the surfaces of the structures in our body.

Even though these lining tissues amount to only about 2 per cent of the weight

of our bodies, they are the source of about 85 per cent of cancers, those known

as carcinomas.

These include cancer of the colon, prostate, pancreas and uterus, along with the

most common type of breast cancer, ductal carcinoma, which develops on milk-duct

lining. (The other main type of cancer, sarcomas, appear in muscles and

connective tissue, and don't have a strong association with vitamin D

insufficiency.)

" Vitamin D is a particularly effective agent in inhibiting abnormal growth or

development of malignancies in epithelial tissues, " says Cedric Garland, a

professor of preventive medicine at the University of California, San Diego.

Although many researchers view cancer as a hopelessly complex disease with

different causes for each tumour type, Dr. Garland, who has been studying

vitamin D for more than three decades, believes the carcinomas have a common

origin in low levels of the vitamin. By his estimate, up to 75 per cent of these

cancers could be prevented if vitamin D levels were raised through supplements.

" I'm convinced that cancer is largely a vitamin D deficiency disease, " he says.

One important function of vitamin D at the gene level that may explain its

anti-cancer properties is that it helps to regulate the production of

E-Cadherin, a type of biological glue that holds cells together. When this glue

is in short supply, it allows epithelial cells to lose adhesion to one another,

permitting some to escape from the tissue they are supposed to be embedded in.

Unconstrained, these cells start to multiply at a greater rate than they

otherwise would and begin forming the lesions that ultimately turn into cancers.

Vitamin D plays a role in telling cells when to die, thus helping to prevent

uncontrolled proliferation and curbing the growth of new blood vessels that

nourish growing tumours.

It may also play a role in diseases unrelated to cancer. A main biological

function of epithelial cells is to be a barrier against viruses and bacteria

that cause infections.

Scientists speculate that when low vitamin D status weakens epithelial cells,

the barrier function is compromised, exposing tissues to attack from

disease-causing agents - in diabetes, for example, by weakening islet cells; in

multiple sclerosis, by weakening glial cells in the nervous system; and in

tuberculosis, by reducing the ability of the lung lining to repulse bacteria,

according to Dr. Garland.

Some medical researchers have even begun to suspect a link between vitamin D

insufficiency and schizophrenia, which occurs 10 per cent more often among those

born in winter and early spring, when vitamin D from sunshine is less available.

Researchers in Australia are testing this hypothesis by studying the brains of

rats born to pregnant mothers deprived of vitamin D - with alarming results. The

vitamin-D-deprived rodent brains had more cell proliferation, enlarged

ventricles and less of a protein necessary for nerve growth.

" What we see is that when you take [vitamin] D out of the brain in the rodent,

you can break their brain basically, " says McGrath, a professor at the

Queensland Brain Institute at the University of Queensland in Brisbane. " We can

change the way their brain develops. "

Dr. McGrath says it is too early to say whether the rodent-brain research

applies to humans. But he adds that " even if only a small fraction of [the cases

of ] schizophrenia could be averted by optimizing maternal nutrition, that is

going to be a really important outcome. "

Mittelstaedt