The Vitamin D Conference just finished
in Victoria was nothing short of spectacular. On the bus
into Victoria, I met a representative from the National
Cancer Institute whose job was simple: her bosses at the NIH wanted
to know if they should fund the flood of grant requests
about vitamin D. Given the quality of the papers
presented, I can't imagine her answer was anything
but yes.
Dr. Tony Norman and Dr. Roger Bouillon, the conference
organizers, had to choose from over 300 submissions from
scientists around the world. The venerable Dr. Bouillon
did not try to back off his recent widely quoted warning
that more than a billion
people in the world are vitamin D deficient.
Both men did a great job balancing presentations on vitamin D
nutrition, vitamin D basic science, and the patentable
vitamin D analogs sought by drug companies. Of course,
I thought more time should have been devoted to vitamin D
nutrition but Dr. Norman pointed out that more time was
devoted to vitamin D nutrition than ever before.
Like Dr. Norman, I am unable to comment on all the presentations
that merited it, or this newsletter would be 50 pages long.
Vitamin D's Many Names
It was painful to hear the scientists use ten different
names (and interchangeably) for vitamin D, for 25-hydroxy
cholecalciferol, and for 1,25-dihydroxy cholecalciferol.
Some even called ergocalciferol vitamin D! Can you
imagine scientists using the same name for cholesterol,
pregnenolone, testosterone, and estradiol? They do exactly
that with vitamin D. Editors of the major journals
will not accept reasonable names like "vitamin D" for
cholecalciferol, "calcidiol" for 25-hydroxy cholecalciferol,
and "calcitriol" for 1,25-dihydroxy cholecalciferol.
The presentations would have been much smoother if scientists
could get together and give vitamin D and its metabolites
common names like other steroid hormones.
Dr. Barbara Gilchrest, who fired Dr. Michael Holick from
one of his professorships several years ago after Holick
wrote a book saying God knew what she was doing when she
created sunlight, gave the Plenary Lecture. Wisely, Dr.
Gilchrest overwhelmed the audience with graphic pictures
of invasive skin cancer to support her argument that sunlight
is evil. Of course, it's harder to show pictures
of invasive colon
cancer, breast
cancer, prostate
cancer, and the 15 other internal cancers caused by
sunlight deprivation.
"Progress Is Impossible Without Change"
However, Dr. Gilchrest is changing her mind. George Bernard
Shaw once said, "Progress is impossible without change;
and those who cannot change their minds, cannot change
anything." Dr. Gilchrest is changing her mind—not
about the evils of sunlight—about vitamin D.
She is in the process of admitting that this miraculous
substance has benefits beyond bone.
Two years ago, she dismissed any concerns about vitamin D
with a "take a multivitamin if you are concerned." Now
she believes the Food and Nutrition Board needs to consider
raising both the Adequate Intake recommendations (how much
one should take every day) as well as the Upper Level (the
amount one can take on your own, without being under a
doctor's care, and without fear of toxicity). My
compliments to Dr. Gilchrest.
The "American Decade Rule"
One of the most interesting things I learned in Victoria
is that scientists from England, Canada, New Zealand, Australia,
and the rest of the world, do not understand the "American
Decade Rule." The rule clearly states that if a U.S.
scientist and a foreign scientist both discover the same
thing in the same decade, the American gets total credit
for it, even if the foreigner discovered it first.
Case in point: the discovery of the potent steroid hormone,
activated vitamin D or calcitriol—a discovery
so important that it regularly starts rumors of a Nobel
Prize. Dr. Holick, Dr. Schnoes, and Dr. DeLuca announced
their discovery of calcitriol in April of 1971. A group
in England, led by Dr. Lawson and Williams, published the
same discovery in Nature, in March of 1971, a
month earlier. Members of the same English group, Dr. Fraser
and Dr. Kodicek, discovered the kidneys make calcitriol
in November of 1970, a full six months earlier. However,
both English discoveries were within a decade of the Americans.
Therefore, the "American Decade Rule" applies
and the Americans get total credit. I was surprised that
scientists from the Commonwealth find the rule so hard
to understand. Proc
Natl Acad Sci U S A. 1971 Apr;68(4):803-4. Nature.
1971 Mar 26;230(5291):228-30. Nature.
1970 Nov 21;228(5273):764-6.
Vitamin D and Neuromuscular Performance
Dr. Heike Bischoff-Ferrari did a wonderful job, not just
presenting her data that optimal vitamin D blood
levels need to be at least 40 ng/mL,
but for presenting Dr. Ed Giovannucci's data (who
had to cancel for personal reasons). Dr. Bischoff-Ferrari
reminded us that periodontal disease in inversely related
to vitamin D blood levels. She also reminded us that
there is strong scientific evidence that vitamin D
improves neuromuscular performance in older people. She
didn't tackle the logical next question: will adequate
levels of one of the most potent steroid hormones in the
body improve neuromuscular performance in younger people,
such as that need for optimal athletic or musical performance?
Philip, whose email to me is above, and other readers of
this newsletter have been telling me yes.
At Least 2,000 IU Needed
Per Day
Dr. Bischoff-Ferrari then presented Dr. Giovannucci's
data that one reduces one's risk of all cancers about
17% for every 10 ng/mL of
vitamin D in their blood. For cancer of the digestive
system, the risk reduction is 43%. His data indicates all
Americans should be taking about 2,000 IU per
day and some Americans need even more to minimize cancer
risk. No one know where the curve flattens out; that is,
no one knows how much further cancer reduction one gets
from 20, 30, or 40 ng/mL incremental
increases in blood levels.
Vitamin D Metabolizing Enzymes
The section on the enzymes that metabolize vitamin D
reminded me how much we don't know about vitamin D.
Millions of Americans take psychiatric and other medications
that interfere with the same system of enzymes, called cytochrome
P-450, that metabolize vitamin D. We've
known for a long time that some medications taken for epilepsy
(Dilantin, phenobarbital, Tegretol) reduce vitamin D
blood levels. However, which medications increase levels?
I have seen a number of cases of higher than expected levels
in patients taking psychiatric medications metabolized
by cytochrome P-450 enzymes and some non-psychiatric medications
interfere with these same enzymes. This practical area
of clinical medicine needs more research.
Seventy-Five Percent Of Women D-Deficient
Dr. Robert Heaney presented by video hookup and made his
quiet but powerful case that about 75% of American
women are vitamin D deficient (levels less than 35 ng/mL),
that about 3,000 units a day are needed to bring 95% of
the population out of the deficient range, and that 10,000
units a day is the safe upper limit. (This does not mean
you should take 10,000 units per day, it means scientists
should be able to study 10,000 unit daily doses without
the bureaucratic difficulty they now encounter).
More Clinical Studies Needed
Dr. Kimball, working with Dr. Reinhold Vieth, presented
data that children (age 10–17) only increased their
average blood level by 11 ng/mL when
given 14,000 units per week for eight weeks and that such
dosing was safe. Dr. Vieth is also trying to fill another
need in vitamin D clinical science. We need a trial
of healthy volunteers taking 20,000 units per day for two
or three years. Do blood levels stabilize with oral dosing
as they do with sun exposure? Does skin production produce
other vitamin D compounds, like dihydrotachysterol,
which inhibits the production of calcitriol and thus protects
against vitamin D toxicity? Do other vitamin D
variants made in the skin induce the metabolism of vitamin D,
lower levels, and protect against toxicity? J
Biol Chem. 1972 Dec 10;247(23):7528-32.
Does 20,000 units a day for years have any ill effects?
Does it affect blood or urine calcium? One study from the
1980s showed 10,000 units a day caused loss in bone density
but they used a vitamin D analog (ergocalciferol)
which is a xenobiotic (generally foreign to the human body).
Therefore, we still don't know what 20,000 units
of real vitamin D (cholecalciferol) would do if given
for several years.
Dr. Bruce Hollis presented data that reminded us of two
overlooked facts: (1) techniques to measure vitamin D
in the blood have significant reliability problems, and
(2) vitamin D is the only steroid hormone system
in the body in which substrate starvation is the rule.
That is, only the vitamin D steroid hormone system
is chronically short of the substance needed (vitamin D)
to fully activate the system. Dr. Reinhold Vieth discussed
the second fact in his chapter in Feldman's most
recent, and invaluable, textbook: Vitamin D.
Dr. Hollis presented evidence in Victoria that levels
of at least 40 ng/mL are
required to normalize the enzyme kinetics of vitamin D.
[When I say vitamin D blood levels, I'm referring
to 25(OH)D levels;
Bruce is studying actual vitamin D levels (cholecalciferol)
as well as 25(OH)D levels].
Dr. Hollis continues giving pregnant and lactating South
Carolina women about 4,000–6,000 units a day in an
ongoing study. We predict easier pregnancies and less depression
in the moms - lower prenatal and perinatal mortality, fewer
birth defects, fewer infections, less diabetes, less psychiatric
illness, less asthma, stronger bones, and higher IQs
in the children.
Most Of The World Is Deficient
Dr. Paul Lips and Dr. Susan Whiting presented upsetting
evidence that vitamin D
deficiency is the rule in most of the world; one exception
is the Scandinavian countries were vitamin D levels
are the highest in Europe, probably due to their cod liver
oil. Unfortunately, hip fractures in these same countries
are the highest in Europe, probably from the excessive
vitamin A in cod liver oil. Stay away from cod liver oil. Osteoporos
Int. 1992 Nov;2(6):298-302.
Upper Limit Needs Revision
Dr. Hathcock did a great job reviewing the evidence that
doses below 10,000 units per day have never been shown
to be toxic and that 10,000, not 2,000, units per day should
be the Upper Limit. He, like so many others, urged the
Food and Nutrition Board to revise their outdated recommendations.
Moreover, I understand from knowledgeable people at the
conference that the Food and Nutrition Board is planning
to do just that. Yes!!!!!!
Higher Blood Levels, Quicker Tan
Dr. Dixon presented fascinating evidence that high vitamin D
blood levels prevent sunburn! Of course, it makes sense.
When vitamin D levels are low, the skin stays as
white as it can to make as much vitamin D as it can,
just in case you ignore Dr. Gilchrest's advice. When
vitamin D levels are high, the skin rapidly tans
to prevent excessive vitamin D skin production. A
number of people have emailed me that observation: now
that their levels are high, they tan very quickly. I've
noticed the same thing.
Athletic Performance and Hair Growth
Dr. Marie Demay presented her basic science research that
vitamin D is involved in hair follicles. I loved
her talk—although she's a scientist and I'm
a psychiatrist so I didn't understand much of what
she said. However, I've always thought that vitamin D
will really take off once science reveals that it's
involved in any of three things: sex, athletic performance,
or hair growth. In Victoria, we saw evidence for neuromuscular
(athletic) performance and hair growth. Two out of three
isn't bad; great job, Dr. Demay! In the way of full
disclosure, my semi-baldness has not improved on vitamin D,
but it has stopped getting worse.
Cancer and Renal Failure
Dr. Cedric Garland recounted how, 26 years ago, he and
his brother Frank first thought about the relationship
between vitamin D and colon
cancer. The brothers, together with colleague Ed Gorham,
were the first to provide epidemiological evidence that vitamin D
deficiency is involved in numerous cancers. Their seminal
1980 paper is going to be reprinted, a well-deserved honor. Int
J Epidemiol. 1980 Sep;9(3):227-31.
Dr. Thadhani and his group from Harvard reviewed their
recent discovery that calcitriol and similar drugs increase
survival in patients with renal failure. He also presented
evidence that renal failure patients have profound deficiencies
of both calcitriol and vitamin D and their vitamin D
deficiency is not corrected by giving calcitriol or
its analogs, which is the current practice.
Vitamin D A Powerful Antibiotic
Of course, Dr. Robert Modlin stole the show when he reported
on his research just published in Science that
vitamin D may be, in effect, a powerful antibiotic.
For the first time, the UCLA group
showed that when researchers add vitamin D to African
American blood, their blood makes more of the natural antibiotics
that humans rely on to fight infection. Dr. Adrian Martineau,
from the Imperial College in London, followed Modlin and
showed vitamin D helped fight tuberculosis, probably
from increasing these same natural antibiotics. Science
has discovered more than 200 of these naturally occurring
antimicrobial peptides; they are especially prevalent in
the upper and lower respiratory tract; at least one inactivates
the influenza virus. Let's not forget that two other
groups have also recently shown the antibiotic potential
of vitamin D. Science.
2006 Mar 24;311(5768):1770-3. Epub 2006 Feb 23. J
Immunol. 2004 Sep 1;173(5):2909-12. FASEB J.
2005 Jul;19(9):1067-77. J
Virol. 1986 Dec;60(3):1068-74.
Evidence of A Multitude of Health Benefits
Two hundred and sixteen papers were relegated to poster
presentations and all 216 of these scientists thought they
should have been chosen to present, as did I. Of course,
that would have meant a month-long conference. I only have
space to mention of few of the most interesting. Dr. Lu
presented evidence that the vitamin D content of
fish is much less than previously thought, including mackerel.
Salmon is okay but the vitamin D almost disappears
when the salmon is fried. Dr. Kimball presented a case
series of 12 patients with multiple sclerosis who are now
on 40,000 units vitamin D a day with an average blood
level of 180 ng/mL (the
highest is about 400 ng/mL)
and they have no evidence of toxicity or calcium disturbances!!!
(Don't do this on your own; they have a very serious
illness, doses were gradually increased, and the patients
are being monitored closely.)
Dr. Hardin, from Columbia University, presented evidence
that blood levels above 50 ng/mL should
help patients with lupus. A group from the University of
Manchester presented the mechanism by which vitamin D
should reduce arteriosclerosis. A group from the University
of Chicago presented evidence that vitamin D should
not only prevent colon
cancer, but help treat it as well. Dr. Robert Scragg
of the University of Auckland presented evidence that ethnic
differences in vitamin D levels explain a significant
proportion of the reason African Americans are more hypertensive
than whites. The group from San Diego presented evidence
that vitamin D
deficiency is intimately involved in breast, colon,
and ovarian cancer.
A group from the University of Manitoba presented evidence
that one-month-old infants tolerate 2,000 units of vitamin
a day for three months quite well without any evidence
of adverse effects. A group from Wake Forest University
demonstrated that higher vitamin D levels were associated
with better neuromuscular (athletic) performance in older
Americans (should help younger Americans too). A group
from the University of Amsterdam showed that the increased
risk of falling from vitamin D
deficiency is much worse in people with a common genetic
variation of the vitamin D receptor. Dr. Chen presented
evidence that plain old vitamin D should prevent prostate
cancer.
Dr. Barsony, of Georgetown University, presented evidence
that low blood sodium is a risk factor for vitamin D
deficiency and that such deficiencies may not be able
to be corrected until the low blood sodium is corrected.
Dr. Barsony really thought "outside the box" to
discover this potentially very important clinical finding.
Dr. Godar presented evidence that young Americans, not
just older Americans, are not getting much vitamin D
from sunlight. Dr. Taylor showed evidence that a significant
number of young children have a previously undetected form
of vitamin D in their blood. (Sunlight triggers the
creation of a number of different versions of vitamin D
in the skin, that's why it's risky to avoid
the sun and only depend on oral vitamin D.) Dr. Patel
and a group from the University of Manchester announced
evidence that vitamin D
deficiency may be involved in inflammatory polyarthritis.
Dr. Grant was involved in six presentations; the most
interesting was his replication of a 1937 finding that
squamous cell skin cancer reduces one's risk for
a number of internal cancers. That's why I used to
be so happy when my dermatologist found a squamous cell
cancer on my skin. However, now that I maintain my level
at about 60 ng/mL,
he hasn't been able to find any new ones. Peller
S, Stephenson CS. Skin irritation and cancer in
the United states Navy.Am J Med Sci: 1937;194:326-333.
Dr. Bulmer and his group from the Royal Victoria Infirmatory
produced evidence that vitamin D may play a role
in allowing fertilized ova to implant in the uterus and
thus enhance fertility. Dr. Reichrath presented evidence
that transplant recipients are at a high risk for vitamin D
deficiency and that 50,000 units once a month may be
the most practical way of ensuring sufficiency. Dr. Selby
from the University of Manchester found the same problem
in patients with chronic pancreatitis. A group from the
University of Tennessee found the same problem in African
Americans with heart failure. A group from Norway confirmed
that cancer patients do better if they are diagnosed when
vitamin D levels are the highest.
Maternal D Deficiency and Brain Damage
Finally, the Australian group headed by Dr. Darryl Eyles
and Dr. John McGrath continue to present their convincing
evidence (confirmed at this meeting by Dr. Abreu and a
group from France) that profound maternal vitamin D
deficiency in mammals causes permanent brain damage
in their offspring. The racial implication of their work
is overwhelming because most of the women in the USA who
are profoundly deficient are African American. Are African
Americans more likely to be born brain damaged than whites?
Would pennies worth of vitamin D improve the disparate
prenatal, perinatal, and postnatal outcome in African Americans?
The sad fact is that McGrath's and Eyles' work
will continue to be ignored because our society has no
way to rationally discuss, assimilate, or act on such racially
charged scientific discoveries.
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