Vitamin
D protects against colorectal cancer by boosting the immune system
A new study by Dana-Farber Cancer Institute investigators
demonstrates that vitamin D can protect some people with colorectal cancer by
perking up the immune system's vigilance against tumor cells.
The research, published January 15, 2015 by the journal Gut,
represents the first time that a link between vitamin D and the immune response
to cancer has been shown in a large human population. The finding adds to a
growing body of research showing that vitamin D - known as the "sunshine
vitamin" because it is produced by the body in response to sunlight
exposure - plays a key role in cancer prevention.
"People with high levels of vitamin D in their bloodstream
have a lower overall risk of developing colorectal cancer," said the
study's senior author, Shuji Ogino, MD, PhD, of Dana-Farber, Harvard School of
Public Health, and Brigham and Women's Hospital. "Laboratory research
suggests that vitamin D boosts immune system function by activating T cells
that recognize and attack cancer cells. In this study, we wanted to determine
if these two phenomena are related: Does vitamin D's role in the immune system
account for the lower rates of colorectal cancer in people with high
circulating levels of the vitamin?"
Ogino and his colleagues theorized that if the two phenomena
were connected, then people with high levels of vitamin D would be less likely
to develop colorectal tumors that are permeated with large numbers of immune
system cells. Colorectal tumors that do develop in these individuals would, by
the same logic, be more resistant to the immune response.
To determine if this is indeed the case, the research team drew
on data from 170,000 participants in the Nurses' Health Study and Health
Professionals Follow-up Study, two long-term health-tracking research projects.
Within this population, researchers compared carefully selected groups of 318
colorectal cancer patients and 624 individuals who were free of cancer. All 942
of them had blood samples drawn in the 1990s, before any developed cancer. The
investigators tested these samples for 25-hydroxyvitamin D, (abbreviated
25(OH)D), a substance produced in the liver from vitamin D.
They found that patients with high amounts of 25(OH)D indeed had
a lower-than-average risk of developing colorectal tumors that were enriched
with immune system cells.
"This is the first study to show evidence
of the effect of vitamin D on anti-cancer immune function in actual patients,
and vindicates basic laboratory discoveries that vitamin D can interact with
the immune system to raise the body's defenses against cancer," Ogino
said. "In the future, we may be able to predict how increasing an
individual's vitamin D intake and immune function can reduce his or her risk of
colorectal cancer."
Low vitamin D levels linked to high risk of
premenopausal breast cancer
A prospective study led by researchers from the University of
California, San Diego School of Medicine has found that low serum vitamin D
levels in the months preceding diagnosis may predict a high risk of
premenopausal breast cancer.
The study of blood levels of 1,200 healthy women found that women
whose serum vitamin D level was low during the three-month period just before
diagnosis had approximately three times the risk of breast cancer as women in
the highest vitamin D group. The study is published online January 2013 in
advance of the print edition of the journal Cancer
Causes and Control.
Several previous studies have shown that low serum levels of
vitamin D are associated with a higher risk of premenopausal breast cancer.
"While the mechanisms by which vitamin D could prevent breast cancer are
not fully understood, this study suggests that the association with low vitamin
D in the blood is strongest late in the development of the cancer, "said
principal investigator Cedric Garland, DrPH, FACE, professor in the Department
of Family and Preventive Medicine at UC San Diego.
Analyses of vitamin D levels measured more than 90 days before
diagnosis have not conclusively established a relationship between serum levels
and risk of premenopausal breast cancer in the present cohort. However, this
new study points to the possibility of a relevant window of time for cancer
prevention in the last three months preceding tumor diagnosis –a time
physiologically critical to the growth of the tumor.
According to Garland, this is likely to be the point at which the
tumor may be most actively recruiting blood vessels required for tumor growth.
"Based on these data, further investigation of the role of vitamin D in
reducing incidence of premenopausal breast cancer, particularly during the late
phases of its development, is warranted," he said.
The new study drew upon 9 million blood serum specimens frozen by
the Department of Defense Serum Repository for routine disease surveillance.
The researchers thawed and analyzed pre-diagnostic samples of serum from 1,200
women whose blood was drawn in the same time frame – samples from 600 women who
later developed breast cancer, and from 600 women who remained healthy.
A 2011 meta-analysis by Garland and colleagues estimated that a
serum level of 50 ng/ml is associated with 50 percent lower risk of breast
cancer. While there are some variations in absorption, those who consume 4000
IU per day of vitamin D from food or a supplement normally would reach a serum
level of 50 ng/ml.
Garland added that a consensus of all available data has shown no
known risk associated with this concentration of vitamin D, which is measured
as serum 25-hydroxyvitamin D. But he urges patients to ask their health care
provider to measure their serum 25(OH)D before substantially increasing vitamin
D intake.
"Reliance should not be placed on different forms of vitamin
D, such as vitamin D2, and megadoses should be avoided except those ordered by
a doctor for short-term use," Garland added.
Pancreatic
cancer risk linked to weak sunlight low vitamin D
Writing in the April 30 2015 online issue of the Journal of
Steroid Biochemistry and Molecular Biology, researchers at University of
California San Diego School of Medicine report pancreatic cancer rates are
highest in countries with the least amount of sunlight. Low sunlight levels
were due to a combination of heavy cloud cover and high latitude.
"If you're living at a high latitude or in a place with a
lot of heavy cloud cover, you can't make vitamin D most of the year, which
results in a higher-than-normal risk of getting pancreatic cancer," said
first author Cedric F. Garland, DrPH, adjunct professor in the Department of
Family Medicine and Public Health and member of UC San Diego Moores Cancer
Center.
"People who live in sunny countries near the equator have
only one-sixth of the age-adjusted incidence rate of pancreatic cancer as those
who live far from it. The importance of sunlight deficiency strongly suggests -
but does not prove - that vitamin D deficiency may contribute to risk of
pancreatic cancer."
Limited foods naturally contain vitamin D. Fatty fish, such as
salmon and tuna, are good sources; beef liver, cheese and egg yolks provide
small amounts. Vitamin D is often added as a fortifying nutrient to milk,
cereals and juices, but experts say most people also require additional vitamin
D to be produce by the body when skin is directly exposed to sunlight.
Specifically, ultraviolet B radiation. Skin exposed to sunshine
indoors through a window will not produce vitamin D. Cloudy skies, shade and
dark-colored skin also reduce vitamin D production.
The UC San Diego team, led by Garland and Edward D. Gorham, PhD,
associate professor, had previously shown that sufficient levels of a
metabolite of vitamin D in the serum, known as 25-hydroxyvitamin D was
associated with substantially lower risk of breast and colorectal cancer. The
current paper is the first to implicate vitamin D deficiency with pancreatic
cancer.
Researchers studied data from 107 countries, taking into account
international differences and possible confounders, such as alcohol
consumption, obesity and smoking. "While these other factors also
contribute to risk, the strong inverse association with cloud-cover adjusted
sunlight persisted even after they were accounted for," said Garland.
UC San Diego researchers had previously identified an
association of high latitude with a higher risk of pancreatic cancer. Garland
said the new study advances that finding by showing that an estimate of solar
ultraviolet B that has been adjusted for heavy cloud cover produces an even
stronger prediction of risk of pancreatic cancer.
Vitamin D influences
racial differences in breast cancer risk
American women of African ancestry are more likely than European
Americans to have estrogen receptor (ER) negative breast cancer. There
continues to be discussion about the role of low levels of vitamin D in the
development of breast cancer for these women. New research published April 2012
in BioMed Central's open access journal Breast
Cancer Research has shown that specific genetic variations in the vitamin D
receptor (VDR) and in CYP24A1 (responsible for deactivating vitamin D) are
associated with an increase in breast cancer risk, particularly for ER negative
breast cancer, for African American women.
When a team of researchers led by Dr Song Yao and Dr Christine
Ambrosone, from Roswell Park Cancer Institute, compared levels of vitamin D in
the blood of women with or without breast cancer they found that severe vitamin
D deficiency in African American women was almost six times more common than in
European American women. However, because low levels of vitamin D can also be
caused by disease, or by treatment, the researchers decided to focus their
studies on genetic variations in VDR and the enzymes responsible for breaking
down vitamin D in the body.
The results showed that African American women with the highest
levels of vitamin D also had a specific variation in VDR. Although this
variation was present in European Americans, it was not associated with
alteration in their levels of vitamin D. African American women with the
specific variation associated with the higher levels of vitamin D, had half the
risk of breast cancer than the women without it.
When the researchers looked in detail at the patterns of genetic
variation for women with ER negative breast cancer, they found that seven SNPs,
in the gene coding for CYP24A1, were associated with ER negative breast cancer
risk, and that two of these seemed to account for the higher risk of ER
negative breast cancer in African American women.
Dr Song
Yao explained, "While it is difficult to determine the exact effect of low
levels of vitamin D on the risk of developing breast cancer, our results show
that these genetic variations, which contribute to the function of vitamin D,
are strongly associated with ER negative breast cancer and may contribute to
the more aggressive breast cancer features seen in African American
women."
Vitamin D increases breast cancer patient survival
Breast cancer patients with high
levels of vitamin D in their blood are twice as likely to survive the disease
as women with low levels of this nutrient, report University of California, San
Diego School of Medicine researchers in the March, 2104 issue of Anticancer Research.
In previous studies, Cedric F.
Garland, DrPH, professor in the Department of Family and Preventive Medicine,
showed that low vitamin D levels were linked to a high risk of premenopausal
breast cancer. That finding, he said, prompted him to question the relationship
between 25-hydroxyvitamin D — a metabolite produced by the body from the
ingestion of vitamin D — and breast cancer survival rates.
Garland and colleagues performed a
statistical analysis of five studies of 25-hydroxyvitamin D obtained at the
time of patient diagnosis and their follow-up for an average of nine years.
Combined, the studies included 4,443 breast cancer patients.
"Vitamin D metabolites
increase communication between cells by switching on a protein that blocks
aggressive cell division," said Garland. "As long as vitamin D
receptors are present tumor growth is prevented and kept from expanding its blood
supply. Vitamin D receptors are not lost until a tumor is very advanced. This
is the reason for better survival in patients whose vitamin D blood levels are
high."
Women in the high serum group had
an average level of 30 nanograms per milliliter (ng/ml) of 25-hydroxyvitamin D
in their blood. The low group averaged 17 ng/ml. The average level in patients
with breast cancer in the United States is 17 ng/ml.
"The study has implications
for including vitamin D as an adjuvant to conventional breast cancer therapy,"
said co-author Heather Hofflich, DO, UC San Diego associate professor in the
Department of Medicine.
Garland recommended randomized
controlled clinical trials to confirm the findings but suggested physicians
consider adding vitamin D into a breast cancer patient's standard care now and
then closely monitor the patient.
"There is no compelling reason
to wait for further studies to incorporate vitamin D supplements into standard
care regimens since a safe dose of vitamin D needed to achieve high serum levels
above 30 nanograms per milliliter has already been established," said
Garland.
A 2011 meta-analysis by Garland and
colleagues estimated that a serum level of 50 ng/ml is associated with 50
percent lower risk of breast cancer. While there are some variations in
absorption, those who consume 4,000 International Units (IU) per day of vitamin
D from food or a supplement normally would reach a serum level of 50 ng/ml.
Garland urged patients to ask their health care provider to measure their
levels before substantially increasing vitamin D intake.
According to the National
Institutes of Health, the current recommended daily allowance for vitamin D is
600 IU for adults and 800 IU for people over 70 years old.
Vitamin D Found to Stimulate a
Protein that Inhibits the Growth of Breast Cancer Cells
Calcitrol,
the active form of vitamin D, has been found to induce a tumor suppressing
protein that can inhibit the growth of breast cancer cells, according to a
study by researcher Sylvia Chistakos, Ph.D., of the UMDNJ-New Jersey Medical
School.
Chistakos,
a professor of biochemistry, has published extensively on the multiple roles of
vitamin D, including inhibition of the growth of malignant cells found in
breast cancer. Her current findings on the vitamin D induced protein that
inhibits breast cancer growth are published in The Journal of Biological Chemistry.
Previous
research had determined that increased serum levels of vitamin D are associated
with an improved diagnosis in patients with breast cancer. Prior to the current
study, little was known about the factors that determine the effect of
calcitrol on inhibiting breast cancer growth, she said.
During
the study, Christakos and co-author Puneet Dhawan, Ph.D., examined the protein
involved in the action that can reduce the growth of vitamin D in breast cancer
cells. “These results provide an important process in which the active form of
vitamin D may work to reduce growth of breast cancer cells,” said Christakos.
“These studies provide a basis for the design of new anticancer agents that can
target the protein as a candidate for breast cancer treatment.”
Vitamin D relieves joint, muscle pain for breast cancer patients
High-dose vitamin D relieves joint and
muscle pain for many breast cancer patients taking estrogen-lowering drugs,
according to a new study from Washington University School of Medicine in St.
Louis.
The drugs, known as aromatase inhibitors,
are commonly prescribed to shrink breast tumors fueled by the hormone estrogen
and help prevent cancer recurrence. They are less toxic than chemotherapy, but
for many patients, the drugs may cause severe musculoskeletal discomfort,
including pain and stiffness in the hands, wrists, knees, hips, lower back,
shoulders and feet.
“About half of patients can experience
these symptoms,” says Antonella L. Rastelli, MD, assistant professor of
medicine and first author of the study published online in the journal Breast Cancer Research and Treatment.
“We don’t know exactly why the pain occurs, but it can be very debilitating —
to the point that patients decide to stop taking aromatase inhibitors.”
Because the drugs reduce cancer
recurrence, finding a way to help patients stay on them is important for
long-term, relapse-free survival, according to Rastelli. Aromatase inhibitors
are prescribed to post-menopausal women for at least five years and often
longer after a breast cancer diagnosis. There is some evidence that patients
who experience the drugs’ side effects are less likely to see their cancer
return, providing even more incentive to help these patients continue taking
them.
It was Rastelli’s colleague, Marie E.
Taylor, MD, assistant professor of radiation oncology, who first noticed that
patients on aromatase inhibitors who experienced this pain found some relief
from high doses of vitamin D.
So Rastelli’s group recruited 60 patients
who reported pain and discomfort associated with anastrozole, one of three
FDA-approved aromatase inhibitors. The patients they studied also had low
vitamin D levels. Half the group was randomly assigned to receive the
recommended daily dose of vitamin D (400 international units) plus a
50,000-unit vitamin D capsule once a week. The other half received the daily
dose of 400 units of vitamin D plus a weekly placebo. All subjects received
1,000 milligrams of calcium daily throughout the study.
Patients in the study reported any pain
they experienced through three different questionnaires. They were asked to
quantify their pain intensity, as well as report how much the pain altered their
mood, affected their work and interfered with relationships and daily
activities. The results show that patients receiving high-dose vitamin D every
week reported significantly less musculoskeletal pain and also were less likely
to experience pain that interfered with daily living.
“High-dose vitamin D seems to be really
effective in reducing the musculoskeletal pain caused by aromatase inhibitors,”
Rastelli says. “Patients who get the vitamin D weekly feel better because their
pain is reduced and sometimes goes away completely. This makes the drugs much
more tolerable. Millions of women worldwide take aromatase inhibitor therapy,
and we may have another ‘tool’ to help them remain on it longer.”
Like anastrozole used in this study, the
other two FDA-approved aromatase inhibitors, letrozole and exemestane, also
cause musculoskeletal pain. Given the similar side effects, Rastelli says
patients on these drugs may also benefit from high-dose vitamin D.
The vitamin used in this study is a
plant-derived type called vitamin D2. Rastelli says it achieves the best
results when given weekly because the body metabolizes it within seven to 10
days. Rastelli and her colleagues did not use high-dose vitamin D3, which
remains in the body longer.
“This was a very carefully conducted
study, and the placebo control makes the findings quite compelling,” says
Matthew J. Ellis, MD, PhD, the study’s senior author and director of the Breast
Cancer Program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital
and Washington University School of Medicine in St. Louis. “We should follow up
these findings further to determine the most efficacious and safe approach to
vitamin D supplementation in our breast cancer patients.”
Since vitamin D helps the body absorb
calcium, too much of it can cause high levels of calcium in the urine, which
may increase the risk of kidney stones. Such possible side effects emphasize
the importance of tracking patients’ urine calcium levels while taking
high-dose vitamin D.
“It’s important to monitor the patients,
but overall it appears to be very safe,” Rastelli says. “Because vitamin D2 is
eliminated from the body so quickly, it’s very hard to overdose.”
In addition to relieving pain, the group
wanted to examine whether vitamin D could protect against the bone loss often
seen in patients taking aromatase inhibitors. The researchers measured each
patient’s bone density at the beginning of the study and again after six
months.
Perhaps because of its role in calcium
absorption, high-dose vitamin D did appear to help maintain bone density at the
neck of the femur, the top of the thighbone near the hip joint. Although the
result did not reach statistical significance, Rastelli calls the result
promising and worth further studies.
“It’s great that we have something as
simple as vitamin D to help patients alleviate some of this pain,” Rastelli
says. “It’s not toxic — it doesn’t cause major side effects. And if it is
actually protecting against bone loss, that’s even better.”
Sunshine vitamin ups bowel cancer survival odds, study
finds
Bowel cancer patients with high
levels of vitamin D in their blood are more likely to survive the disease, a
study shows.
Patients with the highest levels of
vitamin D have half the risk of dying compared with those with the lowest
levels, the findings reveal.
The study is the first to correlate
total blood levels of vitamin D in bowel cancer patients after their diagnosis
– which includes that produced after exposure to sunlight and that obtained
from dietary sources – with their long term survival prospects.
The University of Edinburgh team
tested blood samples from almost 1600 patients after surgery for bowel cancer.
The greatest benefit of vitamin D
was seen in patients with stage 2 disease, at which the tumour may be quite
large but the cancer has not yet spread.
Researchers found that three
quarters of the patients with the highest vitamin D levels were still alive at
the end of five years, compared with less than two thirds of those with the
lowest levels.
The results show that vitamin D is
associated with a much better chance of cancer survival, although the nature of
this relationship is not clear from this study.
The study's authors aim to set up a
clinical trial to test whether taking vitamin D tablets in combination with
chemotherapy can improve bowel cancer survival rates.
Measuring vitamin D levels in bowel
cancer patients could also provide a useful indication of prognosis, the
scientists say.
Professor
Malcolm Dunlop, of the Medical Research Council Human Genetics Unit at the
University of Edinburgh, said: "Our findings are promising but it is
important to note that this is an observational study. We need carefully
designed randomised clinical trials before we can confirm whether taking vitamin
D supplements offers any survival benefit for bowel cancer patients."
Pancreatic
Cancer Risk Lowered By Exposure To Sun
According to a study presented by Rachel
Neale, Ph.D. at the American Association for Cancer Research's Pancreatic
Cancer: Progress and Challenges conference in June, 2012, the risk of
pancreatic cancer is decreased in individuals with a history of skin cancer, as
well as in those born in a location with high levels of ultraviolet radiation
and in people whose skin is sensitive to sun.
Rachel Neale, Ph.D., from Australia's
Queensland Institute of Medical Research led the population-based, case-control
study, which adds to existing conflicting data about sun exposure, vitamin D
gained from sun exposure and the risk of cancer. Neale's study results support
existing ecological data, which suggests that sun exposure has a protective
effect against pancreatic cancer.
Neale commented:
"Several ecological studies,
including one conducted in Australia, have suggested that people living in
areas with high sun exposure have lower risk for pancreatic cancer. However,
some studies of circulating vitamin D indicate that people with high vitamin D
are at increased risk, and one study of vitamin D intake supports this
increased risk."
The study was conducted between 2007 and
2011 and involved 714 Australians from Queensland, who were matched to 709
controls in terms of age and sex. The team questioned all participants
regarding their socio-demographic information and medical history, as well as
about their birth location, history of skin cancer and skin type in terms of
skin color, risk of sunburn sunburn and tanning ability.
The team then assigned the appropriate
ultraviolet radiation level to each birth location using NASA's Total Ozone
Mapping Spectrometer, and divided them into three categories based on the level
of radiation.
They found that the risk for pancreatic
cancer was 24% lower in those born in areas with the highest levels of
ultraviolet radiation as compared with those born in areas of low ultraviolet
radiation.
Despite the fact that all skin types have
a considerable link of being at risk for pancreatic cancer, they discovered
that those with the most sun-sensitive skin had a 49% lower risk than those
with the least sun-sensitive skin. In addition, the risk of pancreatic cancer
was 40% lower in participants with a history of skin cancer or other
sun-related skin lesions compared with those who had not reported skin lesions.
Neale declared:
"There is increasing interest in the
role of sun exposure, which has been largely attributed to the effect of
vitamin D, on cancer incidence and mortality. It is important that we
understand the risks and benefits of sun exposure because it has implications
for public health messages about sun exposure, and possibly about policy
related to vitamin D supplementation or food fortification."
Neale suggests that large cohort studies
are needed in the future, which measure sun exposure and vitamin D levels more
comprehensively. She concludes: "There are several trials of vitamin D
that are either under way or planned, and pooling data from these might give
some clue about vitamin D and pancreatic cancer."
Oral Vitamin D Supplements Fight Prostate Cancer
Higher oral doses of plain vitamin D
raised levels of calcitriol in prostate tissue. Higher prostate levels of
calcitriol, a hormone made from vitamin D, corresponded with lower levels of
the proliferation marker Ki67 and increased levels of cancer growth-inhibitory
microRNAs in prostate cancer cells.
The results not only point to the
mechanisms by which vitamin D affects the rate of prostate cancer growth, but
also indicate that vitamin D may slow the growth of prostate cancer cells — a
key finding given that the role of vitamin D in prostate cancer has been
“controversial, with some suggesting that higher levels of vitamin D should be
avoided,” said Reinhold Vieth, Ph.D., professor at the University of Toronto in
Toronto, Ontario, Canada.
“This study shows calcitriol makes the
foot come off the gas pedal of cancer growth. We are not able to prove that the
speed of the car has slowed down, but it certainly is a good sign,” said Vieth.
“We expect that this early-phase clinical trial will open the door for more
detailed clinical research into the usefulness of vitamin D in the treatment or
prevention of prostate cancer.”
Vieth and colleagues previously reported
that in men who were being monitored regularly for prostate cancer, higher
vitamin D levels slowed the rate of rise in prostate-specific antigen levels.
They randomly assigned 66 men scheduled for radical prostatectomy to daily
vitamin D in doses of 400, 10,000 or 40,000 IU for three to eight weeks before
surgery. Researchers found that calcitriol levels in the prostate increased
progressively with each daily dose of vitamin D, with 40,000 IU showing the
highest levels. These higher levels of calcitriol corresponded with lower
prostate levels of Ki67, a protein that indicates prostate cancer cell growth,
as well as higher levels of specific growth-inhibitory microRNAs.
Vieth stressed that he and his colleagues
do not advocate vitamin D supplementation in doses higher than 4,000 IU daily.
Patients were assigned to the 40,000 IU daily dose because of the short
presurgical time frame available for study, not as a regular regimen.
“Plain vitamin D provides the raw
material to permit the body to take care of its own needs,” he said. “We showed
here that plain vitamin D allows the prostate to regulate its own level of
calcitriol, and at the doses we used, for the time frame we used, it has been
safe with the hoped-for desirable outcomes.”
Vitamin D Fights Lung Cancer
Recent research suggests vitamin D may be
able to stop or prevent cancer. Now, a new study finds an enzyme that plays a
role in metabolizing vitamin D can predict lung cancer survival.
The study, from researchers at the
University of Michigan Comprehensive Cancer Center, suggests that this enzyme
stops the anti-cancer effects of vitamin D.
Levels of the enzyme, called CYP24A1,
were elevated as much as 50 times in lung adenocarcinoma compared with normal
lung tissue. The higher the level of CYP24A1, the more likely tumors were to be
aggressive. About a third of lung cancer patients had high levels of the
enzyme. After five years, those patients had nearly half the survival rate as
patients with low levels of the enzyme.
Researchers then linked this to how
CYP24A1 interacts with calcitriol, the active form of vitamin D. CYP24A1 breaks
down calcitriol, which has a normal and crucial role when kept in check. But
when levels of CYP24A1 climb, the enzyme begins to hinder the positive
anti-cancer effects of vitamin D.
Results of the study appear in Clinical Cancer Research.
Previous studies have linked low levels
of vitamin D to a higher incidence of cancer and worse survival. Researchers
are looking at using vitamin D to help prevent lung cancer from returning and
spreading after surgery. This new study suggests the possibility of using
CYP24A1 levels to personalize this approach to those likely to benefit most.
"Half of lung cancers will recur
after surgery, so it's important to find a way to prevent or delay this
recurrence. A natural compound like vitamin D is attractive because it has few
side effects, but it's even better if we can determine exactly who would
benefit from receiving vitamin D," says study author Nithya Ramnath, M.D.,
associate professor of internal medicine at the U-M Medical School.
Researchers also are working to identify
drugs that block CYP24A1. Blocking the enzyme would reinstate the positive
anti-cancer effects of vitamin D, suggesting that this inhibitor could
potentially be combined with vitamin D treatments.
Higher vitamin D intake needed to reduce cancer risk
Researchers at the University of
California, San Diego School of Medicine and Creighton University School of
Medicine in Omaha have reported that markedly higher intake of vitamin D is
needed to reach blood levels that can prevent or markedly cut the incidence of
breast cancer and several other major diseases than had been originally
thought. The findings are published February 21, 2011 in the journal Anticancer Research.
While these levels are higher than
traditional intakes, they are largely in a range deemed safe for daily use in a
December 2010 report from the National Academy of Sciences Institute of
Medicine.
"We found that daily intakes of
vitamin D by adults in the range of 4000-8000 IU are needed to maintain blood
levels of vitamin D metabolites in the range needed to reduce by about half the
risk of several diseases - breast cancer, colon cancer, multiple sclerosis, and
type 1 diabetes," said Cedric Garland, DrPH, professor of family and
preventive medicine at UC San Diego Moores Cancer Center. "I was surprised
to find that the intakes required to maintain vitamin D status for disease
prevention were so high – much higher than the minimal intake of vitamin D of
400 IU/day that was needed to defeat rickets in the 20th century."
"I was not surprised by this"
said Robert P. Heaney, MD, of Creighton University, a distinguished biomedical
scientist who has studied vitamin D need for several decades. "This result
was what our dose-response studies predicted, but it took a study such as this,
of people leading their everyday lives, to confirm it."
The study reports on a survey of several
thousand volunteers who were taking vitamin D supplements in the dosage range
from 1000 to 10,000 IU/day. Blood studies were conducted to determine the level
of 25-vitamin D – the form in which almost all vitamin D circulates in the
blood.
"Most scientists who are actively
working with vitamin D now believe that 40 to 60 ng/ml is the appropriate
target concentration of 25-vitamin D in the blood for preventing the major
vitamin D-deficiency related diseases, and have joined in a letter on this
topic," said Garland. "Unfortunately, according a recent National
Health and Nutrition Examination Survey, only 10 percent of the US population
has levels in this range, mainly people who work outdoors."
Interest in larger doses was spurred in
December of last year, when a National Academy of Sciences Institute of
Medicine committee identified 4000 IU/day of vitamin D as safe for every day
use by adults and children nine years and older, with intakes in the range of
1000-3000 IU/day for infants and children through age eight years old.
While the IOM committee states that 4000
IU/day is a safe dosage, the recommended minimum daily intake is only 600
IU/day.
"Now that the results of this study
are in, it will become common for almost every adult to take 4000 IU/day,"
Garland said. "This is comfortably under the 10,000 IU/day that the IOM
Committee Report considers as the lower limit of risk, and the benefits are
substantial." He added that people who may have contraindications should
discuss their vitamin D needs with their family doctor.
"Now is the time for virtually
everyone to take more vitamin D to help prevent some major types of cancer,
several other serious illnesses, and fractures," said Heaney.
Vitamin D deficiency common in cancer patients
More than three-quarters of cancer
patients have insufficient levels of vitamin D (25-hydroxy-vitamin D) and the
lowest levels are associated with more advanced cancer, according to a study
presented on October 2, 2011, at the 53rd Annual Meeting of the American
Society for Radiation Oncology (ASTRO).
"Until recently, studies have not
investigated whether vitamin D has an impact on the prognosis or course of
cancer. Researchers are just starting to examine how vitamin D may impact
specific features of cancer, such as the stage or extent of tumor spread,
prognosis, recurrence or relapse of disease, and even sub-types of
cancer," Thomas Churilla, lead author of the study and a medical student
at the Commonwealth Medical College, Scranton, Pa., said.
Researchers sought to determine the
vitamin D levels of patients at Northeast Radiation Oncology Center in Dunmore,
Pa., a community oncology practice, and to see if vitamin D levels were related
to any specific aspects of cancer. The study involved 160 patients with a
median age of 64 years and a 1:1 ratio of men to women. The five most common
primary diagnoses were breast, prostate, lung, thyroid and colorectal cancer. A
total of 77 percent of patients had vitamin D concentrations either deficient
(less than 20 ng/mL) or sub-optimal (20-30 ng/mL). The median serum vitamin D
level was 23.5 ng/mL. Regardless of the age or sex of the patient, levels of
vitamin D were below the median predicted for advanced stage disease in the
patient group.
Patients who were found to be vitamin D
deficient were administered replacement therapy, increasing serum D levels by
an average of 14.9 ng/mL. Investigators will be analyzing if vitamin D
supplementation had an impact on aspects of treatment or survival in the
long-term.
"The benefits of vitamin D outside
of improving bone health are controversial, yet there are various levels of
evidence to support that vitamin D has a role in either the prevention or the
prediction of outcome of cancer," Churilla said. "Further study is
needed to continue to understand the relationship between vitamin D and
cancer."
Vitamin
D acts as a protective agent against the advance of colon cancer
A study conducted by VHIO researchers
confirms that a lack of vitamin D increases the aggressiveness of colon cancer
The indication that vitamin D and its
derivatives have a protective effect against various types of cancer is not
new. In the field of colon cancer, numerous experimental and epidemiological
studies show that vitamin D3 (or cholecalciferol) and some of its derivatives
inhibit the growth of cancerous cells. Researchers at the Vall d'Hebron
Institute of Oncology (VHIO), in collaboration with the Alberto Sols Institute
of Biomedical Research (CSIC-UAB), have confirmed the pivotal role of vitamin
D, specifically its receptor (VDR), in slowing down the action of a key protein
in the carcinogenic transformation process of colon cancer cells. These results
are published in the journal PLoS One.
This protein, known as beta-catenin,
which is normally found in intestinal epithelial cells where it facilitates
their cohesion, builds up in large quantities in other areas of the cells when
the tumour transformation begins. As a result of these changes, the protein is
retained in the cell nucleus, where it facilitate the carcinogenic process, and
this is the point at which vitamin D intervenes, or rather, the vitamin D
receptor (VDR). "Our study has confirmed the pivotal role of the VDR in
controlling the anomalous signal that sparks off the growth and uncontrolled
proliferation of colon cells which, in the final instance, ends up causing a
tumour to emerge", says Héctor Palmer, the coordinator of this study and
head of the VHIO's Stem Cells and Cancer laboratory. He continues, "The
stimulation of this receptor suppresses the action of the beta-catenin protein,
intercepting the series of events that change the intestinal cell into a
malignant tumour cell".
The study was conducted on mice and human
colon cancer cells. The mice were used as a model to replicate the initial
phases of colon cancer. "These findings show that mice of this kind, which
also lack the VDR and hence do not respond to vitamin D, present larger and
more aggressive tumours than mice with the VDR", explains Dr. Palmer, and concludes:
"The number of tumours is not influenced by the absence of VDR, which
would indicate that this factor does not protect against the appearance of the
tumour but does intervene in its growth phase, reducing its
aggressiveness".
The researchers then analysed the effect
of the VDR on human colon cancer cell cultures and observed that the
concentration of the altered protein, beta-catenin, increased in cells without
the VDR. These findings were repeated in the three types of colon cancer cells
studied, and confirmed the results observed in the mice.
In two-thirds of advanced colon cancer
tumours there was a lack of VDR in the cancer cells, and this circumstance
leads us to believe that this loss may contribute to speeding up the growth of
the tumour. The findings of this study confirm this supposition.
In light of these findings, chronic
vitamin D deficiency represents a risk factor in the development of more
aggressive colon tumours. Patients in the initial stages of colon cancer, the
time when the VDR still has a substantial presence in the cells, could benefit
from being treated with vitamin D3. However, this would not be useful in the
advanced stages of the disease when the presence of the VDR is very much
reduced.
The study data support the development of
anti-tumour medicines based on the structure of vitamin D, although their use
in patients will require further research in the next few years.
The body not only obtains vitamin D from
food, especially milk and fish oils, but also manufactures it from exposure to
sunlight. Prolonged exposure is not necessary; just 10 minutes in the sun every
day when it is not at its peak is sufficient to stimulate its production.
During the summer, when we are more likely to sunbathe, it is important to use
the appropriate protective measures against sunburn to avoid future sun damage.
Use high-factor solar protection products and do not expose the skin to the sun
in the middle of the day to protect against skin cancers.
Calcium Plus Vitamin D May Reduce Melanoma Risks
A combination of calcium and vitamin D
may cut the chance of melanoma in half for some women at high risk of
developing this life-threatening skin cancer, according to a new study by
Stanford University School of Medicine researchers.
Using existing data from a large clinical
trial, the study zeroed in on women with a history of non-melanoma skin cancer,
as people with this generally non-fatal disease are more likely to develop the
more lethal illness -- melanoma. The researchers found that women who once had
non-melanoma and took the calcium-vitamin D combination developed 57 percent
fewer melanomas than women with similar histories who were not given the
supplements. Non-melanoma skin cancers, such as basal cell or squamous cell
cancers, are the most common forms of skin cancer.
"In preventive medicine, we want to
target people most at risk for the disease," said dermatologist Jean Tang,
MD, PhD, lead author of the study. "If you previously had a non-melanoma
skin cancer, calcium plus vitamin D might reduce your risk of the more deadly
melanoma."
Tang added a note of caution. The study
found that a daily dose of 1,000 mg calcium plus 400 IU of vitamin D doesn't
provide skin cancer protection for everybody. Women without a history of
non-melanoma skin cancer who took the supplements did not see any reduction of
risk compared with their placebo-group counterparts, according to the research.
The study was published online on June
27, 2011 in the Journal of Clinical
Oncology.
Vitamin D is well-known for its role in
bone growth, but it also affects non-skeletal cells. In many parts of the body,
including the skin, vitamin D controls how quickly cells replicate, a process
that often goes awry in cancer. Reports from various institutions have
suggested that vitamin D is associated with lower risks of colon, breast,
prostate and other cancers. Nonetheless, the Institute of Medicine published a
report last November saying that more research was needed on vitamin D and
calcium, as the evidence was insufficient to prove their having a benefit for
conditions other than bone health.
This study is the second to look at the
effect of vitamin D supplementation on cancer risk with a randomized,
controlled trial.
Tang and colleagues analyzed data from
the Women's Health Initiative, a study that followed 36,000 women ages 50 to 79
for an average of seven years. Half of the women took the daily dose of calcium
and vitamin D as part of the experiment; the other half took a placebo pill.
The WHI calcium plus vitamin D trial was designed to look at the effects of the
supplement on hip fractures and colorectal cancers, but its researchers
collected data on many other health issues, including other cancers.
Tang and colleagues took advantage of the
large and long-term data set provided by the WHI trial to explore whether
vitamin D has a protective effect against skin cancer. "Our results
include the first positive cancer-reducing effect seen from the calcium plus
vitamin D trial," said Teresa Fu, MD, a co-author of the study and a recent
graduate of the School of Medicine.
The lack of protective effect in women
without a history of non-melanoma skin cancer may be due to the amount of
vitamin D given to the patients in the WHI trial. "The patients in the
Women's Health Initiative were given vitamin D at a very low dose, based on
today's knowledge -- only 400 IU per day," said David Feldman, MD,
professor emeritus of endocrinology and a co-author of the study. Furthermore,
patients in the placebo group were allowed to take as much vitamin D as
patients that were provided the calcium and vitamin D supplements, so the
experimental difference between the two groups was small. In light of that
small difference, "it's somewhat surprising that there was an effect on
melanoma risk, and I think many potential benefits of vitamin D may not have
been detected," said Feldman.
Because men were not included in the
trial, the researchers cannot be certain whether the protective effect of the
supplements would also apply to men with a history of non-melanoma skin cancer.
Nonetheless, a 2010 study by Tang demonstrated that elderly men with higher
blood levels of vitamin D have fewer non-melanoma skin cancers.
Even in a large study like the WHI, the
low frequency of melanomas means that the absolute number of cancers was small.
Out of the 36,000 participants, only 176 cases of melanoma were reported.
"That just highlights how large a trial needs to be to capture cancer as
relatively rare as melanoma," said Marcia Stefanick, PhD, the Stanford WHI
principal investigator and senior author of this study.
"These results spur us to do more
studies," said Tang. She is planning multiple lines of research to examine
the potential relationship between vitamin D and cancer prevention, including a
study that will compare blood levels of vitamin D with melanoma outcomes.
Another line of research will examine the effect of larger doses of vitamin D
on the behavior.
Vitamin D lowers kidney cancer risk in men
According to a new study, men employed in
occupations with potential exposure to high levels of sunlight have a reduced
risk of kidney cancer compared with men who were less likely to be exposed to
sunlight at work. The study did not find an association between occupational
sunlight exposure and kidney cancer risk in women. Published early online in CANCER, a peer-reviewed journal of the
American Cancer Society, the study is the largest case-control study of kidney
cancer to investigate the association with occupational sunlight exposure. The
study, however, did not include information on non-occupational sunlight
exposure and does not address directly whether sunlight exposure can help
prevent kidney cancer.
Research suggests that vitamin D, which
is obtained from sun exposure, some foods, and from supplements, may help
prevent some cancers. Vitamin D is metabolized and most active within the
kidneys. Because both the incidence of kidney cancer and the prevalence of
vitamin D deficiency have increased over the past few decades, Sara Karami,
PhD, of the National Cancer Institute in Rockville, MD, and her colleagues
designed a study to explore whether occupational sunlight exposure is
associated with kidney cancer risk.
The study included 1,097 patients with
kidney cancer and 1,476 individuals without cancer from four Central and
Eastern European countries. Demographic and lifetime occupational information
was collected through in-person interviews and occupational sunlight exposure
indices were estimated based on industry and job titles. The investigators
observed a 24 percent to 38 percent reduction in kidney cancer risk with
increasing occupational sunlight exposure among male participants in the study.
No association between occupational sunlight exposure and kidney cancer risk
was observed among females in the study.
The findings suggest that sunlight
exposure may affect kidney cancer risk, although the authors have no
explanation for the apparent differences in risk between men and women. They
offer several hypotheses for the observed differences. Biological or behavioral
differences between men and women may play a role. For example, hormonal
differences may influence the body's response to sunlight exposure, females may
have a higher tendency to use sunscreen on a regular basis, and men may be
prone to working outdoors while shirtless. It is also possible that the
observed gender differences in risk were due to confounding by other unmeasured
kidney cancer risk factors, such as recreational sunlight exposure and physical
activity levels.
While this study's findings raise the
possibility of a link between sunlight exposure and kidney cancer risk,
"they clearly need to be replicated in other populations and in studies
that use better estimates of long-term ultraviolet exposure and vitamin D
intake," said Dr. Karami.
###
Article: "Occupational sunlight
exposure and risk of renal cell carcinoma." Sara Karami, Paolo Boffetta,
Patricia Stewart, Nathaniel Rothman, Katherine L. Hunting, Mustafa Dosemeci,
Sonja I. Berndt, Paul Brennan, Wong-Ho Chow, and Lee E. Moore. CANCER;
Published Online: March 8, 2010 (DOI: 10.1002/cncr.24939).
Vitamin D may raise survival rates among cancer patients
Analysis
finds strongest evidence of benefit in breast, colorectal cancers
Cancer patients
who have higher levels of vitamin D when they are diagnosed tend to have better
survival rates and remain in remission longer than patients who are vitamin
D-deficient, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology &
Metabolism (JCEM).
The body naturally
produces vitamin D after exposure to sunlight and absorbs it from certain
foods. In addition to helping the body absorb the calcium and phosphorus needed
for healthy bones, vitamin D affects a variety of biological processes by
binding to a protein called a vitamin D receptor. This receptor is present in
nearly every cell in the body.
"By reviewing
studies that collectively examined vitamin D levels in 17,332 cancer patients,
our analysis demonstrated that vitamin D levels are linked to better outcomes
in several types of cancer," said one of the study's authors, Hui Wang,
MD, PhD, Professor of the Institute for Nutritional Sciences at the Shanghai
Institutes for Biological Sciences at the Chinese Academy of Sciences in
Shanghai, China. "The results suggest vitamin D may influence the
prognosis for people with breast cancer, colorectal cancer and lymphoma, in
particular."
The meta-analysis
looked at the results of 25 separate studies that measured vitamin D levels in
cancer patients at the time of diagnosis and tracked survival rates. In most of
the research, patients had their vitamin D levels tested before they underwent
any treatment for cancer. The study found a 10 nmol/L increase in vitamin D
levels was tied to a 4 percent increase in survival among people with cancer.
Researchers found
the strongest link between vitamin D levels and survival in breast cancer,
lymphoma and colorectal cancer. There was less evidence of a connection in
people with lung cancer, gastric cancer, prostate cancer, leukemia, melanoma or
Merkel cell carcinoma, but the available data were positive.
"Considering
that vitamin D deficiency is a widespread issue all over the world, it is
important to ensure that everyone has sufficient levels of this important
nutrient," Wang said. "Physicians need to pay close attention to
vitamin D levels in people who have been diagnosed with cancer."
Vitamin D deficiency linked to aggressive prostate cancer
African-American
and European-American men at high risk of prostate cancer have greater odds of
being diagnosed with an aggressive form of the disease if they have a vitamin D
deficiency, according to a new study from Northwestern Medicine® and the
University of Illinois at Chicago (UIC).
Results of the
study were published May 1, 2014 in Clinical
Cancer Research, a journal of the American Association for Cancer Research.
"Vitamin D
deficiency could be a biomarker of advanced prostate tumor progression in large
segments of the general population," said Adam B. Murphy, M.D., lead
author of the study. "More research is needed, but it would be wise for
men to be screened for vitamin D deficiency and treated."
Murphy is an
assistant professor in urology at Northwestern University Feinberg School of
Medicine, a physician at Jesse Brown VA Medical Center and a member of the
Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
"This is the
first study to look at vitamin D deficiency and biopsy outcomes in men at high
risk of prostate cancer," said Rick Kittles, senior author of the study.
"Previous studies focused on vitamin D levels in men either with or
without prostate cancer."
Kittles is an
associate professor in the department of medicine at UIC.
Scientists
examined data collected from a diverse group of more than 600 men from the
Chicago area who had elevated PSA levels or other risk factors for prostate
cancer. Each man was screened for vitamin D deficiency before undergoing a
prostate biopsy.
The authors were
surprised to find that vitamin D deficiency seemed to be a predictor of
aggressive forms of prostate cancer diagnosis in African-American and
European-American men, even after adjusting for potential confounders including
diet, smoking habits, obesity, family history and calcium intake.
"These men,
with severe vitamin D deficiency, had greater odds of advanced grade and
advanced stage of tumors within or outside the prostate," Murphy said.
European-American
men and African-American men had 3.66 times and 4.89 times increased odds of
having aggressive prostate cancer respectively and 2.42 times and 4.22 times
increased odds of having tumor stage T2b or higher, respectively.
African-American
men with severe vitamin D deficiency also had 2.43 times increased odds of
being diagnosed with prostate cancer.
"Vitamin D
deficiency is more common and severe in people with darker skin and it could be
that this deficiency is a contributor to prostate cancer progression among
African-Americans," Murphy said. "Our findings imply that vitamin D
deficiency is a bigger contributor to African-American prostate cancer."
Unless it is
severe, vitamin D deficiency is fairly asymptomatic, so more effort needs to be
put on screening, Murphy said.
"It
is a good idea to get your levels checked on a yearly basis," Murphy said.
"If you are deficient, you and you doctor can make a plan on how to
reverse it through diet, supplements or other therapies."
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