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Sunlight 10,000 IU from 15-20 minutes of midday summer sun Oysters 270 International Units (IU) of vitamin D per half-dozen Dried shiitake mushrooms 172 IU per 100g |
Reinhold
Vieth is frustrated. A thin, bald professor at the University of
Toronto’s Department of Laboratory Medicine and Patho-biology, Vieth is
among the most knowledgeable people in the world on the subject of
vitamin D. He began studying it as a graduate student in 1974 and
hasn’t changed his focus since. “I stick with vitamin D and follow it
where it goes,” he says.
In recent years, vitamin D has been going
to some exciting places. Reports of new and promising studies seem to
emerge almost weekly. A 2007 analysis of vitamin D studies found that
individuals with higher vitamin D levels are significantly – as much as
50 per cent – less likely to develop colorectal cancer. Another 2007
study found that women who took 1,100 International Units (IU) of
vitamin D per day together with a calcium supplement reduced their
overall cancer risk by 60 per cent. And the excitement is not only
about cancer prevention. Low vitamin D levels have been linked to an
increased risk of osteoporosis, heart disease, multiple sclerosis, type
1 diabetes, depression and rheumatoid arthritis, among other diseases.
Perhaps not surprisingly, in light of the other studies, one recent
review of the health records of more than 13,000 Americans found that
individuals with the lowest vitamin D levels were 26 per cent more
likely, in an eight-year period, to die than those with the highest
levels.
So
why is Dr Vieth so frustrated? You might think he’d have cause for
celebration. But for him and other vitamin D researchers around the
world, the good news comes with a bitter aftertaste. They believe they
can prove vitamin D could help millions live longer and be healthier
and yet they have not been able to convince their own governments.
In
the US and Canada, official vitamin D policy is set by the Institute of
Medicine. And in the opinion of Vieth, the current recommendations –
200 International Units per day for people under 50, 400 for people
aged 51-70, and 600 for those 71 and older – are outrageously low.
Bruce Hollis, professor of paediatrics at the Medical University of
South Carolina, calls 400 IU a day “a joke”. That’s because the best
research suggests that to achieve the higher vitamin D blood levels
associated with disease prevention, most adults in the US would need to
take 1,000-2,000 IU a day: five to 10 times more than the current
official recommendation for adults.
In the UK, the government’s
Committee on Medical Aspects of Food and Nutrition Policy has declined
to set a “Reference Nutrient Intake” value for people “leading a normal
lifestyle”, arguing that you can get the vitamin D you need from food
and sunlight. But they fall in line with the Americans where they do
make recommendations: for people confined indoors, the elderly and
pregnant women, they suggest a daily intake of 10 micrograms a day.
That’s equal to 400 IU.
. . .
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Mackerel 643 IU per 100g. Halibut gives you 230 IU per 100g, pickled herring 113 IU per 100 Tinned sardines 23 IU per 12g fish. Tinned salmon gives you 550 IU per 100g, tinned tuna 270 IU per 100g |
Vitamin
D was discovered in the early 20th century as scientists searched for a
cure for rickets, a disease that softens the bones of children, leaving
them bowlegged and deformed. It had been known for some time that
children in cities were more likely to suffer from rickets than those
in the countryside. But it wasn’t until the 1920s that scientists in
the US and UK realised rickets was caused by a vitamin D deficiency,
caused in city kids by lack of sunlight. We obtain our other vitamins
from our food; but while it’s possible to get vitamin D from oily fish
and some other foods, most of the vitamin D in our bodies doesn’t come
from diet at all but from a chemical process that takes place when the
sun’s ultraviolet light strikes our skin.
In the 1950s and 1960s,
when American and other dietary guidelines first specified vitamin D
intakes of up to 400 IU for adults, nobody understood that vitamin D
could do anything other than regulate calcium. And since 200 IU is
enough to prevent rickets in children – assuming they have at least a
moderate amount of calcium in their diet – it was assumed that 200 IU
was sufficient. It was only in the following decades, as scientists
came to understand how vitamin D works in our bodies, that the picture
changed.
After it forms in our skin, vitamin D undergoes two
critical transformations. First our liver metabolises it, turning it
into calcidiol. If you have your vitamin D blood levels checked, it’s
the amount of calcidiol in your blood that will be tested. From the
liver, calcidiol makes its way to the kidneys, where it is turned into
calcitriol, arguably the most potent steroid hormone in the body. In
other words, while vitamin D is lumped together with other vitamins, by
the time our bodies are done with it, it has more in common with
testosterone or oestrogen than with vitamins A or C.
If you
have only a small amount of D in your body, it will all be used by the
kidneys to produce calcitriol and maintain blood calcium levels. But
when there is more vitamin D available, something very different
happens. As scientists have discovered in recent decades, it’s not only
the kidneys that can make calcitriol from the calcidiol produced in the
liver. Many tissues throughout the body can as well. These tissues use
the hormone locally, within the cells, to regulate their behaviour.
“Calcidiol
is like a blank piece of paper,” Vieth explains. “And calcitriol is
like the message written on to it. Calcitriol is needed by our bodies
to convey many kinds of messages, and virtually every cell in our body
has a receptor that can read and respond to it.”
The first real
evidence for the cancer-fighting properties of vitamin D emerged in the
early 1980s, when researchers found that if they added calcitriol to
immature malignant leukaemia cells, the cells would stop growing. They
could only guess why this was, but scientists have since shown that
vitamin D interacts with an unusually large number of genes and has the
apparent ability to turn them on and off.
. . .
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Hard-boiled eggs 26 IU per egg; 25 IU per egg yolk Fortified cows’ milk 250 IU per pint Fortified orange juice 270 IU per pint |
This
new understanding of how vitamin D works in our bodies, together with a
large quantity of evidence of the benefits of higher vitamin D levels,
might make it seem like an obvious move for the world’s governments to
adjust their recommendations for daily intake. But Vieth and other
vitamin D advocates have good reason to think there will be minimal
changes made to dietary guidelines. Last December, the World Health
Organisation’s International Agency for Research on Cancer issued a
465-page report that concluded there was no need to raise vitamin D
recommendations.
The reason is not a lack of research but a lack of
the right kind of research, say vitamin D sceptics. Most evidence for
vitamin D and health is based on epidemiological surveys. Many of these
studies, particularly early ones, were based on geography.
Epidemiologists have found, for example, that multiple sclerosis – a
disease of the central nervous system – and a number of cancers become
more common the farther you move away from the equator. In the US, you
are four times more likely to develop MS if you live in a state that
borders Canada than if you live in the south. The theory is that as you
move away from the equator, you receive less “UVB” ultraviolet sunlight
(UVB is a subtype of UV light and the most important for vitamin D
production), and thus fewer opportunities to make vitamin D in your
skin.
This may sound like persuasive research to lay readers,
but for scientists, such correlations aren’t generally convincing, as
there could be plenty of other possible reasons why people living at
higher latitudes are more likely to suffer from MS.
The more
compelling evidence for the connection between vitamin D and disease
onset comes from the wide range of studies in recent years that have
actually measured vitamin D levels in blood. But even these studies
only show correlations. They can demonstrate, as one Harvard School of
Public Health study did in 2006, that the vitamin D status of healthy
young adults can predict their future risk of developing MS, but they
can’t definitively demonstrate that higher vitamin D levels prevent MS.
It’s possible, for example, that there is another mechanism at work in
the early stage of MS that causes vitamin D levels to drop during the
first stage of a progressive disease (see box below for more on MS).
The link to MS
Multiple
sclerosis is thought to be caused by a mix of environmental and genetic
factors. And while scientists are still trying to unravel how these
interact, a growing body of research points to vitamin D as a key
environmental factor.
In people with MS, the immune system
malfunctions and attacks the protective coating around nerve cells
known as myelin sheaths. The disease can affect sight, balance,
continence, speech and more, and reduces life expectancy. Vitamin D’s
influence on MS – and other autoimmune diseases such as type 1 diabetes
– is thought to be related to the vitamin’s ability to suppress
autoimmune responses.
The link between vitamin D and MS was for
many years thought to be wild speculation. Now more and more studies
point in the same direction: people who have higher levels of vitamin D
in their blood early in life are less likely to get MS later in life.
Also, MS patients have been found to have low levels of vitamin D in
their blood– and the levels appear to be even lower during relapses.
One
small study published this year found that MS patients who took high
doses of vitamin D – an average of 14,000 IU a day for a year – had
significantly fewer relapses than those MS patients who took an average
of 1,000 IU a day. Studies have also shown that vitamin D prevents
experimental autoimmune encephalomyelitis (EAE), the mouse model of
human MS.
Few mainstream researchers would
disagree that a single correlation study should not be given much
weight in determining public policy. It’s only when looked at in
aggregate that these survey studies – together with the many small
clinical trials and our new knowledge of how vitamin D works at the
cellular level – begin to make a powerful case for increasing the
current vitamin D recommendations.
And yet, if the WHO report of
2008 is any indicator, such a case isn’t always strong enough to sway a
sceptical committee. All the recent research notwithstanding, vitamin D
is still missing the gold standard of evidence-based medicine: large,
randomised controlled trials which can demonstrate its ability to
prevent major diseases. The WHO report concludes that “we should wait
for the results of new randomised trials” before changing vitamin D
recommendations.
It’s a position echoed in the UK by the
National Institute of Clinical Excellence (Nice), which advises the
government on whether drugs should be paid for by the state. After
reviewing the vitamin D literature, in 2003 Nice pointed to the absence
of randomised clinical trials and suggested that there was no need even
to recommend vitamin D to pregnant women – a conclusion that was
overruled by the government’s chief medical officer after
paediatricians objected.
. . .
For
Britons, the most alarming aspect of these government responses is that
people living in the UK have so much to lose. For much of the year, it
is impossible in this country to obtain vitamin D from the sun – for
the same reason it is impossible to suffer sunburn. There is simply not
enough UVB ultraviolet radiation in our winter and autumn sunlight. And
unless you happen to consume a lot of oily fish, it’s very hard to get
much vitamin D from your diet. (In addition to oily fish, eggs and
fortified foods have small amounts of vitamin D.) It’s no surprise,
then, that a 2007 study of middle-aged British adults found that 90 per
cent had less-than-optimal levels of vitamin D during winter and
spring. In the US, by comparison, three-quarters of teenagers and
adults are estimated to be deficient in vitamin D.
Advocates of
changes to the vitamin D recommendations in the UK and elsewhere don’t
disagree that large, randomised control trials are important. The
trouble is, trials that could convince policymakers to advise an
across-the-board increase to vitamin D recommendations for all children
and adults might never take place.
There are a number of
obstacles to the research, but the simplest, and biggest, is money.
Vitamin D is not a proprietary compound. It’s cheap and easy to
produce. A bottle of 180 1,000-IU capsules can be purchased online for
about £9. No pharmaceutical company is going to put up the many
millions of dollars necessary to conduct the trials.
Michael
Gleimer, a research fellow at Harvard Medical School who has no
connection to the vitamin D controversy, notes that it is easy for a
medical research fellow to do a small-scale study on something like
vitamin D. “It is non-controversial, easy to get approval for, and
popular-sciency enough that it may land you in the science section of
BBC news,” Gleimer says. “But to do a large, definitive, long-term
study, one needs cash. This is something a pharmaceutical company could
do. But why would they want to push vitamin D? It’s cheap and there is
no patent for it.”
Vitamin D also has to overcome the baggage
of other vitamins. Asked for his thoughts on the US and Canada’s
current daily vitamin D recommendations, Len Lichtenfeld, deputy chief
medical officer of the American Cancer Society, said that “similar
‘signals’ regarding other vitamins and nutritional supplements –
suggesting that they decreased the incidence of certain cancers – have
not been borne out in subsequent randomised clinical trials.”
The
main culprit here is vitamin E, which caused a great deal of excitement
in the early 1990s. The enthusiasm for vitamin E at the time was great
enough to convince the US government to invest millions in just the
sort of large clinical trials that have yet to be conducted for vitamin
D. But E turned out to be a disappointment, showing no benefits
whatsoever in preventing cancer.
There’s a third obstacle in the
way of large clinical trials with vitamin D. Like other nutrients, it
faces a systemic problem. A typical clinical trial follows what Vieth
calls a “pharmaceutical drug company model”, where a group of sick
people are given a carefully selected dose of a drug to see if it makes
a difference to their condition, compared with a second group of sick
people who receive a placebo.
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Fortified tofu 120 IU per 80g Vitamin D capsules 100-5,000 IU; most multivitamin pills contain 400 IU of vitamin D Cod liver oil 450 IU per teaspoon; capsule amounts vary |
The
drawback of this model is that it doesn’t work nearly as well if the
goal of the study is not to determine if a person gets better but to
determine if the substance can prevent you from becoming ill at all.
“It takes a great deal of time and huge population to look at healthy
people and see what develops,” says Mariela Glandt, an endocrinologist
and the former director of the Diabetes Clinical Trials Center at
Hadassah Hospital in Jerusalem. “It’s just much more expensive and
time-consuming.”
Not even the recent announcement of a $20m study by
Harvard Medical School and the Brigham and Women’s Hospital in Boston
is enough to make Vieth optimistic. Funded by National Institutes of
Health and other institutions, the research will look at vitamin D and
omega-3 fatty acids (which have also shown disease-fighting promise) in
the primary prevention of chronic disease in adults ages 60 and over.
If the results are good, they could help make the case for raising
vitamin D recommendations for older adults. But Vieth believes it would
still be difficult to persuade policy-makers of the need to raise
vitamin D levels for everyone. “‘If you start with people older than
age 65 and do clinical trials with them’, policy-makers say, ‘Why
should we impose this drug on everyone in society?’”
And if it
remains challenging to raise enough money to study prevention in older
adults, it’s nearly impossible to find the money to study younger
people; a younger population is less susceptible to disease, so any
convincing study would require an enormous number of participants.
. . .
Then
there is a problem that is more specific to vitamin D. The latest
research suggests that it takes 1,000 IU a day or more to achieve
vitamin D’s anti-cancer benefits. But often when a smaller vitamin D
trial does receive funding, it is conducted with the current lower
vitamin D recommendation – and then fails to prove effective.
These
failures, such as a highly publicised Lancet study in 2005 that found
800 IU of vitamin D and calcium given in prevention trials (trials in
which many participants did not take the supplements regularly) did not
prevent bone fractures, are then used by review committees as grounds
for leaving the current vitamin D recommendations in place.
It
was precisely such studies that convinced the authors of the WHO report
that there was no need for action on vitamin D. The report concluded
that vitamin D recommendations did not need to be raised because there
was not yet evidence that supplementing with 400-840 IU of vitamin D
could prevent cancer. What the conclusion left out, as though the
authors couldn’t imagine anyone taking more than 840 IU, was a
randomised clinical trial which found that 1,110 IU taken daily is
effective in preventing cancer in women.
With so many factors
weighing against a large vitamin D trial for anyone who is not old or
sick with cancer or another serious disease, the best hope for
advocates of higher vitamin D recommendations may be convincing the
medical authorities and the public to take the epidemiology survey
studies more seriously. (Even if a large trial did get off the ground,
it would probably be at least a decade before there were results.)
It’s
not an impossible task. In other instances, the medical community has
been ready to recognise survey evidence: “The evidence favouring
vitamin D is probably as good as the evidence that shows smoking is bad
for you,” Vieth says, explaining that just as smoking is correlated
with certain cancers, so are low vitamin D levels. “But when these
government officials see the same kind of evidence that deals with
vitamin D as they see with smoking they go, ‘Oh wait a minute. We can’t
really trust this.’”
Vieth pauses, as though he can barely stand
to talk about such a miserable state of affairs. “It’s easy to say
‘don’t do something – don’t smoke’. It’s very hard to say ‘take this.
Take vitamin D.’”
Sam Apple is a regular contributor to the FT Weekend Magazine and founder and publisher of the news website TheFasterTimes.com
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Can we overdose?
One
of the debates surrounding vitamin D is whether too much can be toxic.
The US’s Institute of Medicine’s recommendations – unchanged since 1997
– were influenced in part by a 1984 study concluding that 3,800 IU of
vitamin D per day could cause hypercalcemia, or too much calcium in the
blood. Symptoms include kidney stones, vomiting and muscle atrophy.
But
the 1984 study was flawed: it failed to measure the amount of vitamin D
administered; based on the findings of other studies, it now looks as
though subjects were given 100 times more vitamin D than
intended.Moreover, how could it be that 3,800 IU was toxic, when 20
minutes of midday sunbathing in the summer makes at least 10,000 IU of
vitamin D in our bodies?
In 1999, Reinhold Vieth (pictured right)
published a review of vitamin D research in response to the IOM
conclusions. In it, he argued that there was no evidence that amounts
lower than 20,000 IU a day could be toxic. “Throughout my preparation
of this review, I was amazed at the lack of evidence supporting
statements about the toxicity of moderate doses of vitamin D,” Vieth
wrote.
Studies have since shown 10,000 IU a day of vitamin D to
be safe. While any substance will become toxic in excess, vitamin D
researchers today accept that the current vitamin D recommendations
could be more than quadrupled with no fear of toxicity.
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