Vitamin D in a New Light

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There are thirteen
vitamins humans need for growth and development and to maintain
good health. The human body cannot make these essential bio-molecules.
They must be supplied in the diet or by bacteria in the intestine,
except for vitamin D. Skin makes vitamin D when exposed to ultraviolet
B (UVB) radiation from the sun. A light-skinned person will synthesize
20,000 IU (international units) of vitamin D in 20 minutes
sunbathing on a Caribbean beach.

Vitamin D is
also unique in another way. It is the only vitamin that is a hormone,
a type of steroid hormone known as a secosteroid, with three
carbon rings.

Steroid hormones
such as cortisone, estrogen, and testosterone have four carbon rings.
Ultraviolet B radiation in sunlight breaks open one of the rings
in a steroid alcohol present in the skin, 7-dehydrocholesterol,
to form vitamin D (cholecalciferol). The liver changes this molecule
into its circulating form, 25-hydroxyvitamin D (calcidiol,
25[OH]D), the "vitamin D" blood tests measure. Cells throughout
the body absorb 25-hydroxyvitamin D and change it into 1,25-dihydroxyvitamin
D (calcitriol), the active form of vitamin D that attaches directly
to receptors on the DNA of genes in the cell's nucleus.

The vitamin
D hormone system controls the expression of more than 200 genes
and the proteins they produce. In addition to its well-known role
in calcium metabolism, vitamin D activates genes that control cell
growth and programmed cell death (apoptosis), express mediators
that regulate the immune system, and release neurotransmitters (e.g.,
serotonin) that influence one's mental state.

Severe deficiencies
of some vitamins cause vitamin-specific diseases, such as beriberi
(from a lack of vitamin B1, thiamine), pellagra (B3, niacin), pernicious
anemia (B12), and scurvy, (vitamin C). A deficiency in iodine produces
a goiter, mental retardation, and, when severe, cretinism.

Rickets, a
softening and bending of bones in children, first described in 1651,
is another nutritionally-specific disease. It reached epidemic proportions
following the industrial revolution, which began in the 1750s. In
the 19th century, before the importance of exposing children
to sunlight was recognized, the majority of children that lived
in cities with sunless, narrow alleyways and pollution developed
rickets. An autopsy study done in Boston in the late 1800s showed
that more than 80 percent of children had rickets.

Early in the
20th century an investigator found that cod liver oil
could prevent rickets in puppies. The nutritional factor in the
oil that promotes skeletal calcium deposition was named "vitamin
D," alphabetically after already-named vitamins A, B, and C.
Rickets was thought to be another vitamin-deficiency disease, and
the curative agent, a steroid hormone, was mislabeled a "vitamin."

Now, a century
later, a wealth of evidence suggests that rickets, its most florid
manifestation, is the tip of a vitamin D insufficiency/deficiency
iceberg. A lack of Vitamin D can also trigger infections (influenza
and tuberculosis), autoimmune diseases (multiple sclerosis, Type
1 diabetes, rheumatoid arthritis, and inflammatory bowel disease),
cardiovascular disease, and cancer. Practitioners of conventional
medicine (i.e., most MDs) are just beginning to appreciate the true
impact of vitamin D deficiency. In 1990, medical journals published
less than 20 reviews and editorials on vitamin D. Last year they
published more than 300 reviews and editorials on this vitamin/hormone.
This year, on July 19, 2007, even the New England Journal of
Medicine, the bellwether of pharmaceutically-oriented conventional
medicine in the U.S., published a review on vitamin D that addresses
its role in autoimmune diseases, infections, cardiovascular disease,
and cancer (N Engl J Med 2007;357:266–281).

Up until 1980,
doctors thought that vitamin D was only involved in calcium, phosphorus,
and bone metabolism. Then two investigators proposed
that vitamin D and sunlight could reduce the risk of colon cancer.
A growing body of evidence indicates that they were right and that
vitamin D can prevent a whole host of cancers – colon, breast,
lung, pancreatic, ovarian, and prostate cancer among them. Colon
cancer rates are 4 to 6 times higher in North America and Europe,
where solar radiation is less intense, particularly during the winter
months, compared to the incidence of colon cancer near the equator.
People with low blood levels of vitamin D and those who live at
higher latitudes are at increased risk for acquiring various kinds
of cancer. Many epidemiological, cohort, and case control studies
prove, at least on a more likely than not basis, that vitamin D
supplements and adequate exposure to sunlight play an important
role in cancer prevention (Am J Public Health 2006;96:252–261).

There is now
strong scientific evidence that vitamin D does indeed reduce the
risk of cancer. Evidence from a well-conducted, randomized, placebo-controlled,
double-blind trial proves beyond a reasonable doubt that this is
the case, at least with regard to breast cancer. A Creighton University
study has shown that women over the age of 55 who took a 1,100 IU/day
vitamin D supplement, with calcium, and were followed for 4 years
had a highly statistically significant (P <0.005) 75%
reduction in breast cancer (diagnosed after the first 12 months)
compared with women who took a placebo (Am J Clin Nutr 2007;85:1568–1591).

of the genes vitamin D activates make proteins that halt cancer
by inducing apoptosis (programmed cell death), which destroys aberrant
cells before they become cancerous, like adenoma cells in the colon
and rectum
. Others promote cell differentiation and reining
in of out-of-control growth of cancer cells (like prostate
cancer cells
). Vitamin D-expressed genes inhibit angiogenesis,
the formation of new blood vessels that malignant tumors need to
grow, as studies on lung
breast cancers
show. Other genes inhibit metastases, preventing
cancer that arises in one organ from spreading its cells to other
parts of the body, as studied in breast,
and prostate

Vitamin D also
expresses genes that curb cardiovascular disease. One gene controls
the renin-angiotensin system, which when overactive causes hypertension
(high blood pressure). Others stifle the immune system-mediated
inflammatory response that propagates atherosclerosis and congestive
heart failure (Curr Opin Lipidol 2007;18:41–46).

Multiple sclerosis
(MS) is a neurologically devastating disease that afflicts people
with low vitamin D levels. Its victims include the cellist Jacqueline
Du Pré, whose first symptom was loss of sensation in her
fingers, and some 500,000 Americans who currently suffer from this
malady. MS is an autoimmune disease, where the body's immune system
attacks and destroys its own cells. With multiple sclerosis, T cells
in the adaptive immune system, Th1 cells (CD4 T helper type 1 cells),
attack the myelin sheath (insulation) of the axons (nerve fibers)
that neurons (brain cells) use to transmit electrical signals. The
Vitamin D hormone system regulates and tones down the potentially
self-destructive actions of Th1 cells. These cells make their own
1,25-dihydroxyvitamin D if there is a sufficient amount of vitamin
D (25-hydroxyvitamin D) circulating in the blood. Researchers have
shown that the risk of MS decreases as the level of vitamin D in
the blood increases (JAMA 2006;296:2832–2838). People
living at higher latitudes have an increased risk of MS and other
autoimmune diseases. Studies show that people who live below latitude
35 (e.g., Atlanta) until the age of 10 reduce the risk of MS by
50% (Toxicology 2002;181–182:71–78 and Eur J
Clin Nutr 2004;58:1095–1109).

In a study
published earlier this year, researchers evaluated 79 pairs of identical
twins where only one twin in each pair had MS, despite having the
same genetic susceptibility. They found that the MS-free twin had
spent more time outdoors in the sun – during hot days, sun
tanning, and at the beach. The authors conclude that sunshine
is protective against MS
(Neurology 2007;69:381–388).

New research
suggests that influenza is also a disease triggered by vitamin D
deficiency. Influenza virus exists in the population year-round,
but influenza epidemics are seasonal and occur only in the winter
(in northern latitudes), when vitamin D blood levels are at their
nadir. Vitamin D-expressed genes instruct macrophages, the front-line
defenders in the innate immune system, to make antimicrobial peptides,
which are like antibiotics (Science 2006;311:1770–1773).
These peptides attack and destroy influenza virus particles, and
in human carriers keep it at bay. (Neutrophils and natural killer
cells in the innate immune system and epithelial cells lining the
respiratory tract also synthesize these virucidal peptides.) Other
vitamin D-expressed genes rein in macrophages fighting an infection
to keep them from overreacting and releasing too many inflammatory
agents (cytokines) that can damage infected tissue. In the 1918
Spanish flu pandemic, which killed 50 million people, of which 500,000
were Americans, young healthy adults (as happened to my 22-year-old
grandmother) would wake up in the morning feeling well, start drowning
in their own inflammation as the day wore on, and be dead by midnight.
Autopsies showed complete destruction of the epithelial cells lining
the respiratory tract due, as researchers now know, to a macrophage-induced
overly severe inflammatory reaction to the virus. These flu victims
were attacked and killed by their own immune system, something researchers
have found vitamin D can prevent (Epidemiol Infect 2006;134:1129–1140).

clinical trials need to be done to test the vitamin D theory of
influenza. With what we know now, however, perhaps an annual shot
of 600,000 IU of vitamin D (Med J Aust 2005;183:10–12)
would be more effective in preventing influenza than a jab of flu

Our species
evolved in equatorial Africa where the sun, shining directly overhead,
supplies its inhabitants with year-round ultraviolet B photons for
making vitamin D. Our African ancestors absorbed much higher doses
of vitamin D living exposed in that environment compared to the
amount most humans obtain today. A single mutation that occurred
around 50,000 years ago is responsible for the appearance of white
skin in humans. It turns out that a difference in one rung, or base
pair, in the 3 billion-rung DNA ladder that constitutes the human
genome determines the color of one's skin (Science 2005;310:1782–1786).
White skin, with less melanin, synthesizes vitamin D in sunlight
six times faster than dark skin. People possessing this mutation
were able to migrate to higher latitudes, populate Europe, Asia,
and North America, and be able to make enough vitamin D to survive.

The majority
of the world's population now lives above latitude 35 N and is
unable to synthesize vitamin D from sunlight for a period of time
in winter owing to the angle of the sun. At a large solar zenith
angle, ozone in the upper atmosphere will completely block UVB radiation.
In Seattle (47 N) and London (52 N), from October to April UVB
photons are blocked by the atmosphere so one's skin cannot make
vitamin D. (The half-life of circulating vitamin D is approximately
one month.) Making matters worse, even when UVB radiation is available
in sunlight, health authorities, led by the American Academy of
Dermatology, warn people to shield themselves from the sun to avoid
getting skin cancer.

Except for
oily fish like (wild-only) salmon, mackerel, and sardines and cod
liver oil – and also sun-dried mushrooms – very little
vitamin D is naturally present in our food. Milk, orange juice,
butter, and breakfast cereal are fortified with vitamin D, but with
only 100 IU per serving. One would have to drink 200 8-oz. glasses
of milk to obtain as much vitamin D as skin makes fully exposed
to the noonday sun.

The U.S. Food
and Nutrition Board in the Institute of Medicine puts the Recommended
Dietary Allowance (RDA) for vitamin D at 200 IU for children and
adults less than 50 years old, 400 IU for adults age 50–70,
and 800 IU for adults over the age of 70. Most multivitamin preparations
contain 400 IU of vitamin D. These guidelines are directed towards
maintaining bone health and are sufficient to prevent rickets –
but not cancer, cardiovascular disease, multiple sclerosis, or influenza.
Without evidence to support it, the board arbitrarily set the safe
upper limit for vitamin D consumption at 2,000 IU/day.

Vitamin D (25-hydroxyvitamin
D) blood levels, the barometer for vitamin D status, are measured
in nanograms per milliliter (ng/ml) or nanomoles per liter (nmol/l),
where ng/ml = 0.4 nmol/l. Children and adults need a vitamin D blood
level >8 ng/ml to prevent rickets and osteomalacia (demineralization
and softening of bones) respectively. It takes a concentration >20
ng/ml to keep parathyroid hormone levels in a normal range. A level
>34 ng/ml is required to ensure peak intestinal calcium
absorption. Finally, neuromuscular performance steadily improves
in elderly people as vitamin D levels rise up to 50 ng/ml.
Accordingly, a vitamin D blood level <8 ng/ml is regarded as
severely deficient; 8–19, deficient; and 20–29,
insufficient, i.e., too low for good health. A level >30
ng/ml is sufficient, but experts now consider 50–99
ng/ml to be the optimal level of vitamin D. Levels 100–150
ng/ml are excessive and >150 ng/ml, potentially toxic.

A majority
of Americans have insufficient or deficient vitamin D blood levels.
In veterans undergoing heart surgery at the Seattle VA hospital,
I found that 78% had a low vitamin D level: 12% were insufficient;
56%, deficient; and 10% were severely deficient.

In order to
enjoy optimal health, we should maintain a vitamin D blood level
of ≥50–99 ng/ml. Without sun exposure, to reach a level
of 50 ng/ml requires taking a 5,000 IU/day vitamin D supplement.
There are two kinds of vitamin D supplements: vitamin D3 (cholecalciferol),
the kind our skin makes, and vitamin D2 (ergocalciferol), a synthetic
variant made by irradiating plants. Vitamin D2 is only 10–30%
as effective in raising 25-hydroxyvitamin D blood levels compared
to vitamin D3, leading the authors of a recent study conclude, "Vitamin
D2 should not be regarded as a nutrient suitable for supplementation
or fortification" (Am J Clin Nutr 2006;84:694–697).

Concerns about
vitamin D toxicity are overblown, along with those about sun exposure.
As one researcher in the field puts it, "Worrying about vitamin
D toxicity is like worrying about drowning when you're dying of
thirst." The LD50 of vitamin D in dogs (the dose that will
kill half the animals) is 3,520,000 IU/kilogram. One can take a
10,000 IU vitamin D supplement every day, month after month safely,
with no evidence of adverse effect. (Am J Clin Nutr 1999;69:842–856).
A person must consume 50,000 IU a day for several months before
hypercalcemia (an elevated calcium level in the blood, which is
the initial manifestation of vitamin D toxicity) might occur. Vitamin
D in a physiologic dose (5,000 IU/day) prevents the build up of
calcium in blood vessels. (Circulation 1997;96:1755–1760).
If one takes 10,000 IU of vitamin D a day and spends a lot of time
in the sun, it would be prudent to check vitamin D blood level to
ensure that it does not exceed 100 ng/ml.

Sensible sun
exposure should be encouraged, not maligned. If one avoids sunburn,
the sun's health-giving benefits far outweigh its detrimental effects.
A large body of evidence indicates that sunlight does not cause
the most lethal form of skin cancer, malignant melanoma. A U.S.
Navy study found that melanoma occurred more frequently in sailors
who worked indoors all the time. Those who worked outdoors had the
lowest incidence of melanoma. Also, most melanomas appear on parts
of the body that are seldom exposed to sunlight (Arch Environ
Health 1990;45:261–267). Sun exposure is associated with
increased survival from melanoma (J Natl Cancer Inst 2005;97:195–199).
Another study showed that people who had longer lifetime exposure
to the sun without burning were less likely to get melanomas than
those with less exposure (J Invest Dermatol 2003;120:1087–1093.)

The rise in
skin cancers over the last 25 years parallels the rise in use of
sunscreen lotions, which block vitamin D-producing UVB radiation
but not cancer-causing ultraviolet A radiation (UVA). (Newer sunscreen
lotions also block out UVA.) Each year there are 8,000 deaths from
melanoma and 1,500 deaths from nonmelanoma (squamous and basal cell)
skin cancer. Surgical excision of nonmelanoma skin cancers cures
them, except in rare cases where the growth has been allowed to
linger for a long time and metastasize. Dr. John Cannell, Executive
Director of the Vitamin D Council, makes this point: 1,500 deaths
occur each year from non-melanoma skin cancer, but 1,500
deaths occur each day from other cancers that vitamin D in
optimal doses might well prevent. (The Vitamin D Council website
is an excellent source of information on vitamin D.)

The U.S. government
and its citizens currently spend $2,000 billion dollars ($2 trillion)
on "health care," i.e., sickness care, each year. The
cost of taking a 5,000 IU supplement of vitamin D every day for
a year is $22.00. The cost for 300 million Americans taking this
supplement would be $6.6 billion dollars. The number and variety
of diseases that vitamin D at this dose could prevent, starting
with a 50 percent reduction in cancer, is mind-boggling. If everyone
took 5,000 IU/day of vitamin D, the U.S. "health care"
industry would shrink. It would no longer account for 16 percent
of the gross domestic product.

food stores typically do not sell vitamin D3 in 5,000 IU tablets,
but they are readily available online. BIO-TECH
produces both 5,000 and 50,000 IU tablets of Vitamin
D3, which online sites sell. Some people prefer to take one 50,000
IU tablet a week (equivalent to 7,100 IU a day) and a three-day
course of 150,000 IU vitamin D at the first sign of a cold.

Two sites that
sell both "D3-5" (5,000 IU) and "D3-50"
(50,000 IU) are here
and here.

10, 2007

(send him mail)
is a cardiac surgeon and Professor of Surgery at the University
of Washington in Seattle. He is a member of Doctors
for Disaster Preparedness
and writes articles on a variety
of subjects for His web site is

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