Vitamin D3 and cancer

Two New Studies Back
Vitamin D for Cancer Prevention
Vitamin D Affects the Immune System & Healing Wounds on Skin

Researchers Report Levels Needed To Cut Breast, Colon Cancer Risk

February 7, 2007

By Nancy Stringer
ucsdnews

Two new vitamin D studies using a sophisticated form of analysis
called meta-analysis, in which data from multiple reports is combined,
have revealed new prescriptions for possibly preventing up to half of
the cases of breast cancer and two-thirds of the cases of colorectal
cancer in the United States. The work was conducted by a core team of
cancer prevention specialists at the Moores Cancer Center at
University of California, San Diego (UCSD), and colleagues from both
coasts.

The breast cancer study, published online in the current issue of the
Journal of Steroid Biochemistry and Molecular Biology, pooled
dose-response data from two earlier studies - the Harvard Nurses
Health Study and the St. George's Hospital Study - and found that
individuals with the highest blood levels of 25-hydroxyvitamin D, or
25(OH)D, had the lowest risk of breast cancer.

The researchers divided the 1,760 records of individuals in the two
studies into five equal groups, from the lowest blood levels of
25(OH)D (less than 13 nanograms per milliliter, or 13 ng/ml) to the
highest (approximately 52 ng/ml). The data also included whether or
not the individual had developed cancer.

"The data were very clear, showing that individuals in the group with
the lowest blood levels had the highest rates of breast cancer, and
the breast cancer rates dropped as the blood levels of
25-hydroxyvitamin D increased," said study co-author Cedric Garland,
Dr.P.H. "The serum level associated with a 50 percent reduction in
risk could be maintained by taking 2,000 international units of
vitamin D 3 daily plus, when the weather permits, spending 10 to 15
minutes a day in the sun."

The colorectal cancer study, published online February 6 in the
American Journal of Preventive Medicine, is a meta-analysis of five
studies that explored the association of blood levels of 25(OH)D with
risk of colon cancer. All of the studies involved blood collected and
tested for 25 (OH)D levels from healthy volunteer donors who were then
followed for up to 25 years for development of colorectal cancer.

As with the breast cancer study, the dose-response data on a total of
1,448 individuals were put into order by serum 25(OH)D level and then
divided into five equal groups, from the lowest blood levels to the
highest.

"Through this meta-analysis we found that raising the serum level of
25-hydroxyvitamin D to 34 ng/ml would reduce the incidence rates of
colorectal cancer by half," said co-author Edward D. Gorham, Ph.D. "We
project a two-thirds reduction in incidence with serum levels of
46ng/ml, which corresponds to a daily intake of 2,000 IU of vitamin D
3. This would be best achieved with a combination of diet, supplements
and 10 to 15 minutes per day in the sun."

Vitamin D 3 is available through diet, supplements and exposure of the
skin to sunlight, or ultraviolet B (UVB). In the paper, the
researchers underscored the importance of limiting sun exposure such
that the skin does not change color (tan) or burn. For a typical
fair-skinned Caucasian individual, adequate vitamin D could be
photosynthesized safely by spending 10 to 15 minutes in the noontime
sun on a clear day with 50 percent of skin area exposed to the sun.
Darker skinned individuals may require more time in the sun, such as
25 minutes. For people with photosensitivity disorders, or anyone with
a personal or family history of nonmelanoma skin cancer, any amount of
extra sun exposure would be inadvisable.

The meta-analysis on colorectal cancer includes data from the Women's
Health Initiative, which had shown in 2006 that a low dose of vitamin
D did not protect against colorectal cancer within seven years of
follow-up. However, the researchers wrote, the meta-analysis indicates
that a higher dose may reduce its incidence.

"Meta-analysis is an important tool for revealing trends that may not
be apparent in a single study," said co-author Sharif B. Mohr, M.P.H.
"Pooling of independent but similar studies increases precision, and
therefore the confidence level of the findings."

The authors recommend further research to study individuals for the
effect of vitamin D from sunlight, diet and supplements on the risk of
cancer.

****
Vitamin D3 Provides Skin with
Protection from Harmful Microbes
Deficiency in D3 may impact wounds' ability to heal

February 9, 2007

By Debra Kain
ucsdnews

A study by researchers at the UCSD School of Medicine shows that
fluctuations in Vitamin D3 levels control the body's innate immune
response, affecting a skin wound's ability to heal.

Richard L. Gallo, M.D., Ph.D., professor of medicine and chief of
UCSD's Division of Dermatology and the Dermatology section of the
Veterans Affairs San Diego Healthcare System, says that several
unexpected associations between fluctuations of the body's vitamin D3
and infectious disease have emerged in recent investigations.

In a study appearing online February 8 in advance of publication in
the March issue of the Journal of Clinical Investigation, Gallo and
his colleagues look at how the innate immune system is controlled in
the skin, and find that genes controlled by active vitamin D3 play an
essential role in the process.

"Our study shows that skin wounds need vitamin D3 to protect against
infection and begin the normal repair process," said Gallo.
"deficiency in active D3 may compromise the body's innate immune
system which works to resist infection, making a patient more
vulnerable to microbes."

Gallo's lab discovered that an antimicrobial peptide called
cathelicidin is produced by wounds and is necessary to fight
infections. Recently, several studies have begun to link vitamin D to
cathelicidin. Researchers focused on white blood cells called
macrophages that work to destroy invading bacterial microbes.
Macrophages contain toll-like receptors that identify the invaders;
when the receptors sense the presence of bacteria, they trigger
cathelicidin production.

Gallo's team has now discovered that injury stimulates skin cells
called keratinocytes, which surround the wound, to increase the
production of vitamin D3 and that this in turn increases the
expression of genes (CD14 and TLR2) that detect microbes. These genes,
together with active vitamin D3, called 1,25D3, then lead to more
cathelicidin. In both mice and humans, a deficiency in cathelicidin
allows infections to develop more readily.

â??Our finding - that multiple, diverse genes controlled by 1,25D3 are
increased after injury to the skin - suggests that the availability of
D3 is essential to the wound. These responses are a previously
unrecognized part of the human injury response,â?? said Gallo.

Lower concentrations of 1,25D3 in African Americans, likely due to a
decreased ability to absorb vitamin D from sunlight, correlate with
increased susceptibility to infection. In addition, 1,25D3 has been
suggested to be an immune-modifying agent in pulmonary tuberculosis.

As a result of this and previous studies, Gallo and his colleagues are
beginning clinical trials at UCSD Medical Center with both oral and
topical vitamin D3. Normal volunteers, and patients with disorders in
antimicrobial peptide production such as atopic dermatitis and acne,
are being studied to determine if vitamin D3 can improve their natural
immune defenses.

Additional contributors to the paper include Jorgen Schauber, Robert
A. Dorschner, Alvin B. Coda, Amanda S. Bachau and David Kiken of
UCSD's Division of Dermatology and VA San Diego Healthcare System;
Philip T. Liu and Robert L. Modlin, Division of Dermatology, David
Geffen School of Medicine, UCLA; Yolanda R. Helfrich and Sewon Kang
Department of Dermatology, University of Michigan; Hashem Z. Alalieh
and Daniel D. BIkle, Department of Medicine, VA Medical Center, UCSF;
Andreas Steinmeyer and Ulrich Zügel, Schering AG, Berlin, Gemany

The research was sponsored by the National Institutes of Health and
the Veterans Administration.

.