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The Potential of Vitamin D in Cancer

Prevention
The first hint of a correlation between vitamin D and cancer
arose in the 1930’S when it was observed that those living in
areas with higher exposure to sunlight had a lower incidence
of cancer.

Explaining the link between cancer and sunlight proved


difficult. At the time, vitamin D had only just been discovered
(1921) and its mode of production, by the skin in response to
ultraviolet (UV) light had yet to discovered.

It was not until the 1980s that anyone seriously considered


that vitamin D might account for the differences in cancer
rates. Initially, two epidemiologists (the Garland brothers) at
the University of California in San Diego discovered that
being exposed to sunlight reduced the risk of colon cancer.
Later they were able to show that exposure to sunlight and
the incidence of breast cancer were also strongly related.

Then another researcher, Schwartz discovered that the


same was true of prostate cancer.

The Garland brothers then published data supporting the


role of vitamin D as as an explanation of the correlation
between cancer rates and sun exposure.

By 2008 there were over 63 epidemiological studies in the


world literature showing the correlation between low vitamin
D levels and the development of cancer.

The incidence of over sixteen different types of cancer,


which includes all the most common killers has shown some
correlation with low levels of vitamin D.

Out of the 63 epidemiology studies mentioned above, 30


studied colon cancer, 26 prostate cancer, 13 breast cancer
and 7 ovarian cancer. The majority of these studies showed
a correlation between low level of vitamin D and an
increased incidence of cancer.
Studies previously conducted in animals had predicted this
effect. There are multiple animal and cell-based studies that
have demonstrated the anti-cancer effect of vitamin D.
While all these data amounts to a very strong signal that
vitamin D levels play an important role in preventing cancer,
the scientific community remained skeptical as no one had
conducted a prospective double blind placebo trial to confirm
these findings. The double bind placebo controlled trial is
considered the gold standard in clinical trial design. In such
studies patients are placed on either the active compound or
placebo (sugar pill) and followed to monitor the effects.

Eventually, such a study was done with Vitamin D by Dr.


Joan Lappe at Creighton University in Omaha, Nebraska.
In her study she treated women over the age of 55 with
either 1100IU of vitamin D and calcium or calcium alone or
placebo. She followed the patients for four years and
monitored the incidence of cancer. The results were very
convincing

Over the four year treatment period, the group receiving


vitamin D and calcium developed 60% fewer cases of
cancer than occurred in the placebo group.

Dr. Lappe then reanalyzed the data looking at the incidence


of cancer occurring during years 2-4 of the trial. This was
done because it was highly likely that the cases of cancer
that occurred during the first year of the study were already
present when the patients entered the trial but were too early
to be detected.

In this analysis Dr. Lappe found that the vitamin D


treated group demonstrated a 77% reduction in the
incidence of cancer compared to the placebo group.

In addition, Dr. Lappe explored the relationship between


blood levels of vitamin D and the incidence of cancer. This
analysis showed that every 25 nmol/L (10ng/ml) increase in
vitamin D levels resulted in a 35% reduction in the risk of
developing cancer.
In a study conducted in France, physicians monitored
vitamin D levels prior to renal transplantation and then
followed the patients to determine cancer rates in those with
deficient, insufficient and adequate levels. At least 85% of
the patients had deficient or insufficient levels of vitamin D.
The incidence of cancer during the follow up period was
13.7% in the deficient group, 7% in the insufficient and
only 3.7% in the group with normal vitamin D levels.
These numbers show an excellent dose response, ie the
higher the level of vitamin D the lower the incidence of
cancer. Such a dose response is a strong indicator of cause
and effect which is so often missing in epidemiology studies.

In Germany, 3299 patients admitted to hospital for coronary


angiography had their vitamin D levels measured and were then
followed for almost eight years. During the follow-up period, there
were 95 deaths due to cancer. Those with the highest levels of
vitamin D had a 55% reduction in the risk of death from cancer
compared to the group with the lowest levels. In this study levels
above 30ng/ml were considered to be high and only 10% of the
patient population had levels this high. Only one of the 95
patients who died from cancer was in the group with the highest
vitamin D levels.

The vitamin D council in the USA now recommended


that doses of 2000IU in the summer and 5000IU in the
winter are needed to keep vitamin D at optimal levels. This
is especially for populations living high above the equator.

The Canadian Oncology Society now recommends that all


Canadians take vitamin D supplements to reduce the risk of
cancer.

However, the Canadians are not the only people suffering


from Vitamin D deficiency. Such deficiency is widespread.
Almost anyone who does not live in a sunny environment
and expose themselves to the sun on a regular basis is likely
to have less than optimal levels.

Recently a major health care provider in the US, Aurora


Healthcare, has recommended that all Wisconsin residents
take vitamin D and has started a program to educate its
physicians about the dangers of vitamin D deficiency.

The Chief Medical Officer of Scotland has stated also that


the government of Scotland should initiate a program to
ensure all citizens increase their intake of vitamin D. This
northern region of the UK sees little of the sun and has some
of the worst rates of cardiovascular disease and cancer in
the world.

Lung Cancer Prevention


Recently, Professor Garland of the University of California,
San Diego published an analysis of the relationship between
latitude, ultraviolet (UV) exposure and the incidence of lung
cancer. (Latitude and UV exposure, both determine the
quantity of vitamin D produced) Data on the incidence of
lung cancer was gathered from 111 countries.
This analysis showed that the higher the latitude the higher
the incidence of lung cancer in both men and women. Living
at lower latitudes and,thus being exposed to more sun light
resulted in a reduction in the risk of developing lung
cancer by 45% for men and 65% in women. The lower
degree of protection seen in men is believed to be due to
their increased rate of smoking compared to women.

Calculating the degree of ultraviolet exposure at various


latitudes, the relationship with lung cancer was inversely
associated with the amount of UV exposure --the higher the
exposure to UV the lower the incidence of lung cancer. The
correlation with UV exposure at different latitudes was highly
statistically significant in men (P=0.003) and even more so in
women (P=0.0002).

Even the amount of cloud cover correlated with the


incidence of lung cancer. The more cloud cover (thus less
UV) the higher the rate of lung cancer.

Professor Garland has also published similar results for


breast cancer, renal cancer and endometrial cancer.

In another study in Finland, nearly 7000 subjects had their


vitamin D levels checked and then followed for up to 24
years to monitor the incidence of lung cancer. Females
with the highest levels of vitamin D showed a 84%
reduction in the risk of developing lung cancer. The
incidence of lung cancer in men was not seen to depend
on vitamin D status although if the younger males and
females were examined as a group they also showed a
66% reduction in the risk of developing lung cancer. As
in the Garland study, older men did not show any protective
effect from higher levels of vitamin D, and it is postulated
that this is due to their much higher incidence of heavy
smoking.
Colon Cancer Prevention
The link between vitamin D levels and colon cancer is
perhaps the strongest of all the types of cancer. The
connection was first noted in 1980 in a study by Garland et
al who noted that deaths from colon cancer were much rarer
in sunny parts of the country. The incidence of colon cancer
was 4-6 times higher in northern areas compared to
countries near the equator.

Several epidemiology studies were then conducted that also


showed a correlation between dietary intake of vitamin D
and the incidence of colorectal cancer. The higher the intake
of vitamin D, the lower the incidence of cancer, usually
around a 50% reduction. Because dietary intake of vitamin D
is only a small contributor to total body vitamin D, these
results suggested that colorectal cancer may be very
sensitive to vitamin D levels. (Dietary intake is rarely more
than 600 IU per day whereas the body can make as much as
20,000 IU in a few minutes in strong sunshine).

Finally studies were done where the blood level of vitamin D


was actually measured, and it was shown that the higher the
level the less the chance of developing colon cancer. The
correlation was extremely strong. The risk of colon cancer
was reduced five fold if vitamin D levels were between 33-
41ng/ml. A similar relationship was found in a another study
conducted in Finland. Vitamin D levels were sorted into four
quartiles and a 63% reduction in the risk of colorectal cancer
was demonstrated between the highest and lowest quartiles.
Interestingly, the four quartiles showed a very convincing
dose response curve which is strong evidence for a cause
and effect relationship. The study also demonstrated that the
Finns were very vitamin D deficient with the average level
being only 13ng/ml.

A prospective epidemiology study was published in


November 2007 by Dr. Freedman of NCI. In this study
participants had their baseline vitamin D levels measured
and were followed for up to twelve years, and the overall
incidence of cancer noted. Over 16000 patients were
monitored in this study. It concluded that deaths due to
cancer during the follow up period were unrelated to
baseline vitamin D levels.

This study was widely reported in the media under such


headlines as "Maybe vitamin D Isn't the Answer After All"
However, despite the negative conclusion and media
reporting, the numbers in the publication revealed a different
story. Looking at individual types of cancer there was a 72%
reduction in the incidence of colorectal cancer between
the groups of patients with the highest and lowest levels
(<20ng/ml vis >32ng/ml) of vitamin D. This difference was
highly statistically significant. In addition, there was also a
72% reduction in the incidence of breast cancer, which
because of small numbers was not statistically significant but
still a very interesting signal of activity.

The fact that a single estimation of the vitamin D level can


predict the incidence of any form of cancer twelve years in
the future is remarkable and might suggest that the cancer in
question is extremely sensitive to vitamin D.

Finally in another study conducted at Harvard School of


Public Health, 179 colorectal cancer patients were matched
with control subjects and their vitamin D levels compared.
Again those with the highest versus the lowest levels of
vitamin D demonstrated a 50% reduction in the risk of
colorectal cancer.

Breast Cancer Prevention


The role of vitamin D in preventing breast cancer has been
extensively studied and the results encouraging.

During the 1980's and 90's several epidemiological studies


showed that women living in sunny areas of the US had
much lower rates of breast cancer than those living in less
sunny areas. Overall these studies showed the risk of
developing breast cancer was three to five times lower in
sunny areas of the country. Later studies compared the
incidence of breast cancer in women with high or low dietary
intake of vitamin D. Theses studies generally showed a
small protective effect of high dietary intake. However, it is
known that dietary intake accounts of only a small fraction of
our total vitamin D levels as the vast majority (over 90%) is
made in the skin following exposure to UV radiation.

Possibly the largest study looking at high and low dietary


intake was published in 2007. This study estimated calcium
and vitamin D intake in over 10,000 premenopausal and
over 20,000 post menopausal women who where followed
for ten years. There was approximately a 40% reduction in
the risk of developing breast cancer in premenopausal
women who had the highest calcium and vitamin D intake.
No effect was seen in postmenopausal women.
In 2008 another large epidemiological study was published
where breast cancer rates in 107 countries were studied in
relationship to both modeled and measured vitamin D levels.
It was demonstrated that those living in Southern areas had
almost a 60% reduction in their risk of developing breast
cancer compared to those living in Northern areas.

Finally in 2008, a study was published where actual blood


levels of vitamin D were measured in post-menopausal
breast cancer patients and compared to levels in a control
population without breast cancer. Between the groups of
patients with the lowest and highest levels of vitamin D there
was a almost a 70% reduction in the risk of developing
breast cancer. A strong trend was also seen across the
various levels of vitamin D showing that the lower the level
the greater the risk of developing breast cancer. The authors
concluded that the data strongly suggest a protective effect
for post-menopausal women with higher vitamin D level.

In the following year the same group repeated their work in a


pre-menopausal population of breast cancer patients again
comparing their vitamin D levels to matched controls. Once
again comparing the groups with the lowest and highest
levels of vitamin D there was almost a 60% reduction in the
risk of breast cancer. There was also a good trend seen
across the various levels showing that the lower the level of
vitamin d the greater the risk.

Prostate Cancer Prevention


A connection between prostate cancer and vitamin D levels
was first proposed in 1990 by Schwartz et al. His paper
pointed out that all the major risk factors for prostate cancer:
age, darked skin and northern latitudes are assoicated with a
reduced production of vitamin D. Mortality from prostate
cancer was inversely correlated with ultraviolet radiation.

Men in the US have ten times the risk of developing prostate


cancer than Japanese men. This has also been linked to
vitamin D consumption as Japanese men have a higher
intake due to their high intake of fatty fish which is a good
source of vitamin D. The correlation between prostate
cancer deaths and exposure to sunlight was again explored
and a significant negative correlation was demonstrated.
Several studies were then published showing no correlation
between vitamin D and the risk of prostate cancer.

However, in 2000 another study was published in which


young mens level of calcidiol (vitamin D precursor) was
measured and the men followed for the development of
prostate cancer. This showed than men with low levels
(below 16ng/ml) were three times more likely to develop
prostate cancer and six times more likely to develop
agressive invasive cancer than men with higher levels.

By this time there was a great deal of lab and animal data to
support the use of calcidiol in prostate cancer and in 2003
and extensive review of these data was published and
concluded that "adequate vitamin D should be maintained,
not only for bone health in men and women but because it
might decrease the risk of prostate cancer and prevent
metastatic disease should it develop."

Researchers in Norway then published work showing that


men diagnosed with prostate cancer during seasons with
more sunlight had a significantly better prognosis that those
diagnosed with the condition at other times of the year.

Then in 2004 results of a trial in which 15 men with


advanced prostate cancer were treated with 2000 IU of
vitamin D3. Impressivily,14 of the 15 men showed a reducing
in, or prevention of further rises in PSA showing that vitamin
D could play a role in prosate cancer.

Preventing Pancreatic Cancer


Two large long-term studies have shown that adults who
have a higher dietary intake of vitamin D (300-400 IU) have
almost half the risk of developing pancreatic cancer than
those with less than 150 IU vitmain D in their diet.

The researchers followed 120,000 subjects in the Health


Professionals Follow-Up study and the Nurses Health Study.
Between the two studies there were 365 cases of pancreatic
cancer.
Interestingly, even subjects who consumed only 150-299 IU
daily had a 22% reduction in their risk of developing the
condition. This graduated response suggests a dose
response which is a very good indicator of a true cause and
effect relationship.

In 2008 another study was published suggesting that sun


exposure may be associated with higher death rates in
pancreatic cancer patients. However, no blood levels were
measured in this study and the results would appear to
contradict those seen in many other studies. No other study
has suggested that high vitamin D levels are detrimental.