Researchers at Emory University are learning how vitamins and minerals in the diet can stimulate or prevent the appearance of colon cancer.
Emory investigators will present their findings on biological markers that could influence colon cancer risk in three abstracts at the American Association for Cancer Research meeting in San Diego.
In a clinical study of 92 patients, supplementing diet with calcium and vitamin D appeared to increase the levels of a protein called Bax that controls programmed cell death in the colon. More Bax might be pushing pre-cancerous cells into programmed cell death, says Emory researcher Veronika Fedirko, who will present her team's results.
Previous studies have shown that calcium and vitamin D tend to reduce colon cancer risk.
"We were pleased that the effects of calcium and vitamin D were visible enough in this small study to be significant and reportable," Fedirko says. "We will have to fully evaluate each marker's strength as we accumulate more data."
The studies of colorectal biopsy samples are part of a larger effort to identify a portfolio of measurements that together can gauge someone's risk of getting colon cancer, says Roberd Bostick, MD, MPH, professor of epidemiology at Emory's Rollins School of Public Health.
"We want to have the equivalent of measuring cholesterol or high blood pressure, but for colon cancer instead of heart disease," Bostick says. "These measurements will describe the climate of risk in the colon rather than spotting individual tumors or cells that may become tumors."
Bostick has plans for developing non-invasive blood or urine tests for colon cancer risk.
Bostick and his colleagues demonstrates in a 200-patient case-control study that high levels of calcium and vitamin D together are associated with increased levels of E-cadherin, which moderates colon cells' movement and proliferation.
A third abstract on the same case-control study to be presented at the same meeting, shows that high levels of iron in the diet are linked to low levels of APC, a protein whose absence in colon cancer cells leads to their runaway growth.
Bostick and his colleagues are participating in a ten-year multi-center study of the effects of increased vitamin D and calcium and biomarker-guided treatment of colon cancer recurrence. The study involves almost 2,500 people nationwide who have regular colonoscopies.
The Bostick team's research is funded by the National Cancer Institute and the Wilson and Anne Franklin Foundation.
Showing posts with label Vitamins. Show all posts
Showing posts with label Vitamins. Show all posts
Saturday, 10 May 2008
Twin Findings Raise Hopes Of Improved Anemia Treatments
A new understanding of how red blood cell production is controlled could lead to improvements in the treatment of the blood disorder anaemia, according to West Australian medical researchers.
The findings are reported in two papers published in Blood, the journal of the American Society of Hematology, by a group of Australian scientists, led by Western Australian Institute for Medical Research (WAIMR) Director Peter Klinken and his Laboratory for Cancer Medicine.
One of the papers shows how the gene Hls5, which was discovered by Professor Klinken's team, affects red cell production.
"We have established that Hls5 impedes the maturation of immature red blood cells which has provided us with a much better understanding of what Hls5 does and how it is linked with the development of leukaemias and cancers," he said.
"Another arm of our research has revealed that thyroid hormone, which it was already established affected metabolism, also contributes to red blood cell formation -- which was previously unknown."
Professor Klinken said both findings opened the door to exploring new ways of treating a range of anaemias.
"Anaemias develop where a person's blood is low in red blood cells so the two discoveries we have made may provide an insight into how to turn these conditions around," he said.
"Our findings indicate that minor changes in Hls5 levels can have a big impact and so the possibility of modulating this gene to generate new treatments is significant.
"As a number of patients don't respond to erythropoietin (EPO) -- the current form of hormone therapy for anaemias -- this new knowledge will hopefully lead to alternative treatments."
The research being conducted by Professor Klinken and his team is funded by the National Health and Medical Research Council and ASX-listed Perth-based biotechnology company BioPharmica.
Anaemia occurs when the amount of haemoglobin (which is found in red blood cells) drops below normal. Haemoglobin is necessary for the transportation of oxygen throughout the body.
It can be caused by iron or vitamin deficiency, blood loss, a chronic illness, a genetic or acquired defect or disease or through the use of some medications.
The findings are reported in two papers published in Blood, the journal of the American Society of Hematology, by a group of Australian scientists, led by Western Australian Institute for Medical Research (WAIMR) Director Peter Klinken and his Laboratory for Cancer Medicine.
One of the papers shows how the gene Hls5, which was discovered by Professor Klinken's team, affects red cell production.
"We have established that Hls5 impedes the maturation of immature red blood cells which has provided us with a much better understanding of what Hls5 does and how it is linked with the development of leukaemias and cancers," he said.
"Another arm of our research has revealed that thyroid hormone, which it was already established affected metabolism, also contributes to red blood cell formation -- which was previously unknown."
Professor Klinken said both findings opened the door to exploring new ways of treating a range of anaemias.
"Anaemias develop where a person's blood is low in red blood cells so the two discoveries we have made may provide an insight into how to turn these conditions around," he said.
"Our findings indicate that minor changes in Hls5 levels can have a big impact and so the possibility of modulating this gene to generate new treatments is significant.
"As a number of patients don't respond to erythropoietin (EPO) -- the current form of hormone therapy for anaemias -- this new knowledge will hopefully lead to alternative treatments."
The research being conducted by Professor Klinken and his team is funded by the National Health and Medical Research Council and ASX-listed Perth-based biotechnology company BioPharmica.
Anaemia occurs when the amount of haemoglobin (which is found in red blood cells) drops below normal. Haemoglobin is necessary for the transportation of oxygen throughout the body.
It can be caused by iron or vitamin deficiency, blood loss, a chronic illness, a genetic or acquired defect or disease or through the use of some medications.
Synthetic Vitamin D Helps Prevent Some Breast Cancers, Animal Study Suggests
Researchers at Rutgers University have found that, in animal studies, a synthetic form of active vitamin D has a substantive preventive effect on the development of both estrogen receptor (ER)-positive and ER-negative breast cancers. Unlike many of the other synthetic vitamin D agents that have been tested in humans, this compound, known as Gemini 0097, shows no toxicity, they report.
The research team found that daily injections of Gemini 0097 cut growth of ER-positive cancer by 60 percent in rat studies, and reduced ER-negative breast cancer by half in mice.
"These are very promising findings, especially because no toxicity is observed," said researcher Hong Jin Lee, a graduate student at Rutgers. Lee works in the laboratory of lead investigator Nanjoo Suh, Ph.D., an assistant professor at the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers, the State University of New Jersey. Suh said that Gemini 0097 likely did not cause the most common vitamin D toxicity, an overload of calcium in blood known as hypercalcemia, because the compound has an extra side chain of chemicals.
"It is quite different from the natural shape of active vitamin D," she said. "Because the binding affinity of Gemini 0097 with vitamin D receptor is low that may contribute to the lower toxicity, but the efficacy stays the same or even better."
Epidemiologic studies have shown that use of vitamin D is beneficial in preventing colon cancer, but studies in prostate and breast cancer have yielded mixed conclusions, Suh says.
Vitamin D is a pro-hormone that is produced in the skin after exposure to sunlight. Vitamin D dietary supplements are converted into an active, useful form by metabolism in the liver and kidneys. Although the active form of vitamin D has been tested as a cancer treatment, the higher doses needed for prevention or treatment have typically produced intolerable side effects in clinical trials, Suh says.
In this study, the researchers tested 60 novel Gemini vitamin compounds, with Gemini 0097 performing the best, Lee says.
In one set of studies, the researchers exposed rats to a mammary carcinogen, then injected groups of 15 animals with different doses of Gemini 0097. They found that the lowest dose had little effect but higher doses slowed the growth of resultant ER-positive tumors by 60 percent, compared with a group of control rats. Some treated rats developed small mammary tumors and some developed none at all, says Lee. "The data are very convincing," he said.
In a second, similar experiment in a mouse model of ER-negative breast cancer, mice treated with Gemini vitamin D had 50 percent fewer tumors than did control mice.
The researchers analyzed tumor samples from both the rats and the mice and discovered that Gemini 0097 prevents tumorigenesis by increasing expression of the p21 protein, which arrests the cell cycle, and by inducing insulin-like growth factor binding protein--3 (IGFBP-3), which slows down cell proliferation.
"These data are from animal studies, and we need more data before these compounds can be tested in humans," said Suh. "Still, we are hopeful that we have found a way of providing vitamin D without toxicity that has a significant effect on cancer prevention."
This research was presented at the 2008 Annual Meeting of the American Association for Cancer Research, April 12-16, 2008.
The research team found that daily injections of Gemini 0097 cut growth of ER-positive cancer by 60 percent in rat studies, and reduced ER-negative breast cancer by half in mice.
"These are very promising findings, especially because no toxicity is observed," said researcher Hong Jin Lee, a graduate student at Rutgers. Lee works in the laboratory of lead investigator Nanjoo Suh, Ph.D., an assistant professor at the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers, the State University of New Jersey. Suh said that Gemini 0097 likely did not cause the most common vitamin D toxicity, an overload of calcium in blood known as hypercalcemia, because the compound has an extra side chain of chemicals.
"It is quite different from the natural shape of active vitamin D," she said. "Because the binding affinity of Gemini 0097 with vitamin D receptor is low that may contribute to the lower toxicity, but the efficacy stays the same or even better."
Epidemiologic studies have shown that use of vitamin D is beneficial in preventing colon cancer, but studies in prostate and breast cancer have yielded mixed conclusions, Suh says.
Vitamin D is a pro-hormone that is produced in the skin after exposure to sunlight. Vitamin D dietary supplements are converted into an active, useful form by metabolism in the liver and kidneys. Although the active form of vitamin D has been tested as a cancer treatment, the higher doses needed for prevention or treatment have typically produced intolerable side effects in clinical trials, Suh says.
In this study, the researchers tested 60 novel Gemini vitamin compounds, with Gemini 0097 performing the best, Lee says.
In one set of studies, the researchers exposed rats to a mammary carcinogen, then injected groups of 15 animals with different doses of Gemini 0097. They found that the lowest dose had little effect but higher doses slowed the growth of resultant ER-positive tumors by 60 percent, compared with a group of control rats. Some treated rats developed small mammary tumors and some developed none at all, says Lee. "The data are very convincing," he said.
In a second, similar experiment in a mouse model of ER-negative breast cancer, mice treated with Gemini vitamin D had 50 percent fewer tumors than did control mice.
The researchers analyzed tumor samples from both the rats and the mice and discovered that Gemini 0097 prevents tumorigenesis by increasing expression of the p21 protein, which arrests the cell cycle, and by inducing insulin-like growth factor binding protein--3 (IGFBP-3), which slows down cell proliferation.
"These data are from animal studies, and we need more data before these compounds can be tested in humans," said Suh. "Still, we are hopeful that we have found a way of providing vitamin D without toxicity that has a significant effect on cancer prevention."
This research was presented at the 2008 Annual Meeting of the American Association for Cancer Research, April 12-16, 2008.
Vitamin E May Help Alzheimer's Patients Live Longer, Study Suggests
People with Alzheimer's disease who take vitamin E appear to live longer than those who don't take vitamin E, according to new research.
For the study, researchers followed 847 people with Alzheimer's disease for an average of five years. About two-thirds of the group took 1,000 international units of vitamin E twice a day along with an Alzheimer's drug (a cholinesterase inhibitor). Less than 10 percent of the group took vitamin E alone and approximately 15 percent did not take vitamin E.
The study found people who took vitamin E, with or without a cholinesterase inhibitor, were 26 percent less likely to die than people who didn't take vitamin E.
"Vitamin E has previously been shown to delay the progression of moderately severe Alzheimer's disease. Now, we've been able to show that vitamin E appears to increase the survival time of Alzheimer's patients as well," said study author Valory Pavlik, PhD, with Baylor College of Medicine's Alzheimer's Disease and Memory Disorders Center in Houston, TX, and member of the American Academy of Neurology. "This is particularly important because recent studies in heart disease patients have questioned whether vitamin E is beneficial for survival."
In addition, the study found vitamin E plus a cholinesterase inhibitor may be more beneficial than taking either agent alone. "Our findings show that people who took a cholinesterase inhibitor without vitamin E did not have a survival benefit," said Pavlik. "More research needs to be done to determine why this may be the case."
In addition to vitamin E supplements, some vegetables oils, nuts, and green leafy vegetables are main food sources of vitamin E. Some fortified cereals in the United States also contain vitamin E. "The daily amount of vitamin E taken by patients in this study was much higher than what is currently recommended for the general population," said Pavlik.
This research was presented at the American Academy of Neurology 60th Anniversary Annual Meeting in Chicago, April 12--19, 2008.
For the study, researchers followed 847 people with Alzheimer's disease for an average of five years. About two-thirds of the group took 1,000 international units of vitamin E twice a day along with an Alzheimer's drug (a cholinesterase inhibitor). Less than 10 percent of the group took vitamin E alone and approximately 15 percent did not take vitamin E.
The study found people who took vitamin E, with or without a cholinesterase inhibitor, were 26 percent less likely to die than people who didn't take vitamin E.
"Vitamin E has previously been shown to delay the progression of moderately severe Alzheimer's disease. Now, we've been able to show that vitamin E appears to increase the survival time of Alzheimer's patients as well," said study author Valory Pavlik, PhD, with Baylor College of Medicine's Alzheimer's Disease and Memory Disorders Center in Houston, TX, and member of the American Academy of Neurology. "This is particularly important because recent studies in heart disease patients have questioned whether vitamin E is beneficial for survival."
In addition, the study found vitamin E plus a cholinesterase inhibitor may be more beneficial than taking either agent alone. "Our findings show that people who took a cholinesterase inhibitor without vitamin E did not have a survival benefit," said Pavlik. "More research needs to be done to determine why this may be the case."
In addition to vitamin E supplements, some vegetables oils, nuts, and green leafy vegetables are main food sources of vitamin E. Some fortified cereals in the United States also contain vitamin E. "The daily amount of vitamin E taken by patients in this study was much higher than what is currently recommended for the general population," said Pavlik.
This research was presented at the American Academy of Neurology 60th Anniversary Annual Meeting in Chicago, April 12--19, 2008.
Variants Of Vitamin D Receptor Linked To Increased Risk Of Breast Cancer
Genetic variations in the body's receptor for vitamin D could increase the risk of breast cancer in postmenopausal women, according to a new study.
Jenny Chang-Claude of the Division of Cancer Epidemiology, at the German Cancer Research Center, in Heidelberg, and colleagues there and at the Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Germany, undertook a population-based case-control study involving 1,408 patients and 2,612 control individuals.
The researchers explain that vitamin D intake and serum concentrations of its metabolites have been associated with a decreased risk of developing breast cancer. The vitamin plays a known role in controlling calcium levels and influences the differentiation of cells and so could play a part in preventing the runaway proliferation of cells characteristic with cancer.
Previous studies regarding the association between vitamin D and breast cancer have been inconsistent in their conclusions.
Chang-Claude and her colleagues have investigated variations in the gene encoding the vitamin D receptor protein. They found that there were no differences in the biomarker for vitamin D, 25-hydroxyvitamin D, between women with two well-known genetic variations, the polymorphisms FokI and TaqI, and two functional putative variants, VDR-5132 and Cdx2, in the gene for the receptor. Moreover, they found no relationship between the presence of these polymorphisms and overall risk of postmenopausal breast cancer.
However, they found a significant increase in the risk of estrogen receptor (ER) positive tumours among women with the TaqI genetic variant. This suggests the involvement of estrogen metabolism in the anticancer activity of vitamin D.
"Further studies focusing on the influence of genetic variations on vitamin D receptor functionality, activity and concentration are now needed" says Chang-Claude.
Journal reference: Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk. Sascha Abbas, Alexandra Nieters, Jakob Linseisen, Tracy Slanger, Silke Kropp, Elke J Mutschelknauss, Dieter Flesch-Janys and Jenny Chang-Claude. Breast Cancer Research (in press)
Jenny Chang-Claude of the Division of Cancer Epidemiology, at the German Cancer Research Center, in Heidelberg, and colleagues there and at the Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Germany, undertook a population-based case-control study involving 1,408 patients and 2,612 control individuals.
The researchers explain that vitamin D intake and serum concentrations of its metabolites have been associated with a decreased risk of developing breast cancer. The vitamin plays a known role in controlling calcium levels and influences the differentiation of cells and so could play a part in preventing the runaway proliferation of cells characteristic with cancer.
Previous studies regarding the association between vitamin D and breast cancer have been inconsistent in their conclusions.
Chang-Claude and her colleagues have investigated variations in the gene encoding the vitamin D receptor protein. They found that there were no differences in the biomarker for vitamin D, 25-hydroxyvitamin D, between women with two well-known genetic variations, the polymorphisms FokI and TaqI, and two functional putative variants, VDR-5132 and Cdx2, in the gene for the receptor. Moreover, they found no relationship between the presence of these polymorphisms and overall risk of postmenopausal breast cancer.
However, they found a significant increase in the risk of estrogen receptor (ER) positive tumours among women with the TaqI genetic variant. This suggests the involvement of estrogen metabolism in the anticancer activity of vitamin D.
"Further studies focusing on the influence of genetic variations on vitamin D receptor functionality, activity and concentration are now needed" says Chang-Claude.
Journal reference: Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk. Sascha Abbas, Alexandra Nieters, Jakob Linseisen, Tracy Slanger, Silke Kropp, Elke J Mutschelknauss, Dieter Flesch-Janys and Jenny Chang-Claude. Breast Cancer Research (in press)
High Blood Levels Of Vitamin D Protect Women From Breast Cancer, Study Suggests
A connection between vitamin D level and the risk of developing breast cancer has been implicated for a long time, but its clinical relevance had not yet been proven. Sascha Abbas and colleagues from the working group headed by Dr. Jenny Chang-Claude at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), collaborating with researchers of the University Hospitals in Hamburg-Eppendorf, have now obtained clear results:
While previous studies had concentrated chiefly on nutritional vitamin D, the researchers have now investigated the complete vitamin D status. To this end, they studied 25-hydroxyvitamin D (25(OH)D) as a marker for both endogenous vitamin D and vitamin D from food intake.
The result of the study involving 1,394 breast cancer patients and an equal number of healthy women after menopause was surprisingly clear: Women with a very low blood level of 25(OH)D have a considerably increased breast cancer risk. The effect was found to be strongest in women who were not taking hormones for relief of menopausal symptoms. However, the authors note that, in this retrospective study, diagnosis-related factors such as chemotherapy or lack of sunlight after prolonged hospital stays might have contributed to low vitamin levels of breast cancer patients.
In addition, the investigators focused on the vitamin D receptor. The gene of this receptor is found in several variants known as polymorphisms. The research team of the DKFZ and Eppendorf Hospitals investigated the effect of four of these polymorphisms on the risk of developing breast cancer. They found out that carriers of the Taql polymorphism have a slightly increased risk of breast tumors that carry receptors for the female sex hormone estrogen on their surface. No effects on the overall breast cancer risk were found. A possible explanation offered by the authors is that vitamin D can exert its cancer-preventing effect by counteracting the growth-promoting effect of estrogens.
Besides its cancer-preventing influence with effects on cell growth, cell differentiation and programmed cell death (apoptosis), vitamin D regulates, above all, the calcium metabolism in our body. Foods that are particularly rich in vitamin D include seafish (cod liver oil),
While previous studies had concentrated chiefly on nutritional vitamin D, the researchers have now investigated the complete vitamin D status. To this end, they studied 25-hydroxyvitamin D (25(OH)D) as a marker for both endogenous vitamin D and vitamin D from food intake.
The result of the study involving 1,394 breast cancer patients and an equal number of healthy women after menopause was surprisingly clear: Women with a very low blood level of 25(OH)D have a considerably increased breast cancer risk. The effect was found to be strongest in women who were not taking hormones for relief of menopausal symptoms. However, the authors note that, in this retrospective study, diagnosis-related factors such as chemotherapy or lack of sunlight after prolonged hospital stays might have contributed to low vitamin levels of breast cancer patients.
In addition, the investigators focused on the vitamin D receptor. The gene of this receptor is found in several variants known as polymorphisms. The research team of the DKFZ and Eppendorf Hospitals investigated the effect of four of these polymorphisms on the risk of developing breast cancer. They found out that carriers of the Taql polymorphism have a slightly increased risk of breast tumors that carry receptors for the female sex hormone estrogen on their surface. No effects on the overall breast cancer risk were found. A possible explanation offered by the authors is that vitamin D can exert its cancer-preventing effect by counteracting the growth-promoting effect of estrogens.
Besides its cancer-preventing influence with effects on cell growth, cell differentiation and programmed cell death (apoptosis), vitamin D regulates, above all, the calcium metabolism in our body. Foods that are particularly rich in vitamin D include seafish (cod liver oil),
Vitamin D Important In Brain Development And Function
In a definitive critical review, scientists at Children's Hospital & Research Center Oakland ask whether there is convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction. Joyce C. McCann, Ph.D., assistant staff scientist and Bruce N. Ames, Ph.D., senior scientist at Children's Hospital Oakland Research Institute (CHORI) conclude that there is ample biological evidence to suggest an important role for vitamin D in brain development and function, and that supplementation for groups chronically low in vitamin D is warranted. Their conclusions will be published on April 22, 2008 in the Federation of American Societies for Experimental Biology (FASEB) Journal.
"This critical analysis of vitamin D function and the brain is a model of careful thinking about nutrition and behavior", says Gerald Weissmann, MD, Editor-in-Chief of the FASEB Journal "One wishes that all studies of nutritional supplements or requirements were this thoughtful. Drs. McCann and Ames deftly show that while vitamin D has an important role in the development and function of the brain, its exact effects on behavior remain unclear. Pointing to the need for further study, the authors argue for vitamin D supplementation in groups at risk."
Vitamin D has long been known to promote healthy bones by regulating calcium levels in the body. Lack of sufficient vitamin D in very young children results in rickets, which can be easily prevented by vitamin D supplements. Only recently the scientific community has become aware of a much broader role for vitamin D. For example, we now know that, in addition to its role in maintaining bone health, vitamin D is involved in differentiation of tissues during development and in proper functioning of the immune system.
In fact, over 900 different genes are now known to be able to bind the vitamin D receptor, through which vitamin D mediates its effects. In addition to protecting against rickets, evidence now strongly indicates that a plentiful supply of vitamin D helps to protect against bone fractures in the elderly. Evidence also continues to accumulate suggesting a beneficial role for vitamin D in protecting against autoimmune diseases, including multiple sclerosis and type I diabetes, as well as some forms of cancer, particularly colorectal and breast.
Vitamin D is present in only a few foods (e.g., fatty fish), and is also added to fortified milk, but our supply typically comes mostly from exposure to ultraviolet rays (UV) in sunlight. UV from the sun converts a biochemical in the skin to vitamin D, which is then metabolized to calcitriol, its active form and an important hormone. Formation of vitamin D by UV can be 6 times more efficient in light skin than dark skin, which is an important cause of the known widespread vitamin D deficiency among African Americans living in northern latitudes. Dark skin has been selected during evolution because it protects against the burning UV rays of the sun in the tropics.
White skin has been selected for allowing as much UV exposure to make sufficient vitamin D in Northern (high) latitudes. Thus, fair-skinned northerners are at risk in Australia or Arizona for sunburns and UV-induced cancer, while dark-skinned people in the Northern U.S. or European latitudes with little exposure to the sun are at risk for rickets, bone fractures and possibly other diseases including several types of cancer due to a lack of vitamin D. Fortunately sun-screens and vitamin D supplements are inexpensive.
McCann & Ames point out that evidence for vitamin D's involvement in brain function includes the wide distribution of vitamin D receptors throughout the brain. They also discuss vitamin D's ability to affect proteins in the brain known to be directly involved in learning and memory, motor control, and possibly even maternal and social behavior. The review also discusses studies in both humans and animals that present suggestive though not definitive evidence of cognitive or behavioral consequences of vitamin D inadequacy. The authors discuss possible reasons for the apparent discrepancy between the biological and behavioral evidence, and suggest new, possibly clarifying avenues of research.
Many vitamin D experts advise that the currently recommended level of vitamin D intake is much too low and should be raised to protect against bone fractures and possibly cancer in addition to rickets (2). Indeed, even using present guidelines, too many Americans have low vitamin D blood levels. McCann & Ames propose that, despite uncertainty regarding all of the deleterious effects of vitamin D inadequacy, the evidence overall indicates that supplementation, which is both inexpensive and prudent, is warranted for groups whose vitamin D status is exceptionally low, particularly nursing infants, the elderly, and African Americans (e.g., see (3)).
This review is the fourth in a series by McCann & Ames that critically evaluate scientific evidence linking deficiencies in micronutrients (the approximately 40 vitamins, minerals, amino acids, and fatty acids required for the body to function) to brain function. Other reviews in the series discuss the long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) (4, 5), choline (6), and iron (7).
"This critical analysis of vitamin D function and the brain is a model of careful thinking about nutrition and behavior", says Gerald Weissmann, MD, Editor-in-Chief of the FASEB Journal "One wishes that all studies of nutritional supplements or requirements were this thoughtful. Drs. McCann and Ames deftly show that while vitamin D has an important role in the development and function of the brain, its exact effects on behavior remain unclear. Pointing to the need for further study, the authors argue for vitamin D supplementation in groups at risk."
Vitamin D has long been known to promote healthy bones by regulating calcium levels in the body. Lack of sufficient vitamin D in very young children results in rickets, which can be easily prevented by vitamin D supplements. Only recently the scientific community has become aware of a much broader role for vitamin D. For example, we now know that, in addition to its role in maintaining bone health, vitamin D is involved in differentiation of tissues during development and in proper functioning of the immune system.
In fact, over 900 different genes are now known to be able to bind the vitamin D receptor, through which vitamin D mediates its effects. In addition to protecting against rickets, evidence now strongly indicates that a plentiful supply of vitamin D helps to protect against bone fractures in the elderly. Evidence also continues to accumulate suggesting a beneficial role for vitamin D in protecting against autoimmune diseases, including multiple sclerosis and type I diabetes, as well as some forms of cancer, particularly colorectal and breast.
Vitamin D is present in only a few foods (e.g., fatty fish), and is also added to fortified milk, but our supply typically comes mostly from exposure to ultraviolet rays (UV) in sunlight. UV from the sun converts a biochemical in the skin to vitamin D, which is then metabolized to calcitriol, its active form and an important hormone. Formation of vitamin D by UV can be 6 times more efficient in light skin than dark skin, which is an important cause of the known widespread vitamin D deficiency among African Americans living in northern latitudes. Dark skin has been selected during evolution because it protects against the burning UV rays of the sun in the tropics.
White skin has been selected for allowing as much UV exposure to make sufficient vitamin D in Northern (high) latitudes. Thus, fair-skinned northerners are at risk in Australia or Arizona for sunburns and UV-induced cancer, while dark-skinned people in the Northern U.S. or European latitudes with little exposure to the sun are at risk for rickets, bone fractures and possibly other diseases including several types of cancer due to a lack of vitamin D. Fortunately sun-screens and vitamin D supplements are inexpensive.
McCann & Ames point out that evidence for vitamin D's involvement in brain function includes the wide distribution of vitamin D receptors throughout the brain. They also discuss vitamin D's ability to affect proteins in the brain known to be directly involved in learning and memory, motor control, and possibly even maternal and social behavior. The review also discusses studies in both humans and animals that present suggestive though not definitive evidence of cognitive or behavioral consequences of vitamin D inadequacy. The authors discuss possible reasons for the apparent discrepancy between the biological and behavioral evidence, and suggest new, possibly clarifying avenues of research.
Many vitamin D experts advise that the currently recommended level of vitamin D intake is much too low and should be raised to protect against bone fractures and possibly cancer in addition to rickets (2). Indeed, even using present guidelines, too many Americans have low vitamin D blood levels. McCann & Ames propose that, despite uncertainty regarding all of the deleterious effects of vitamin D inadequacy, the evidence overall indicates that supplementation, which is both inexpensive and prudent, is warranted for groups whose vitamin D status is exceptionally low, particularly nursing infants, the elderly, and African Americans (e.g., see (3)).
This review is the fourth in a series by McCann & Ames that critically evaluate scientific evidence linking deficiencies in micronutrients (the approximately 40 vitamins, minerals, amino acids, and fatty acids required for the body to function) to brain function. Other reviews in the series discuss the long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) (4, 5), choline (6), and iron (7).
Low Blood Levels Of Vitamin D May Be Associated With Depression In Older Adults
Older adults with low blood levels of vitamin D and high blood levels of a hormone secreted by the parathyroid glands may have a higher risk of depression, according to a new report .
About 13 percent of older individuals have symptoms of depression, and other researchers have speculated that vitamin D may be linked to depression and other psychiatric illnesses, according to background information in the article. "Underlying causes of vitamin D deficiency such as less sun exposure as a result of decreased outdoor activity, different housing or clothing habits and decreased vitamin intake may be secondary to depression, but depression may also be the consequence of poor vitamin D status," the authors write. "Moreover, poor vitamin D status causes an increase in serum parathyroid hormone levels." Overactive parathyroid glands are frequently accompanied by symptoms of depression that disappear after treatment of the condition.
Witte J. G. Hoogendijk, M.D., Ph.D., and colleagues at VU University Medical Center, Vrije Universiteit Amsterdam, the Netherlands, measured blood levels of vitamin D and parathyroid hormone and assessed symptoms of depression among 1,282 community residents age 65 to 95. Of those individuals, 26 had a diagnosis of major depressive disorder, 169 had minor depression and 1,087 were not depressed. The average blood vitamin D level was 21 nanograms per milliliter and the average parathyroid hormone level was 3.6 picograms per milliliter.
Blood vitamin D levels were 14 percent lower in individuals with major and minor depression (average, 19 nanograms per milliliter) compared with non-depressed participants (average, 22 nanograms per milliliter). In addition, parathyroid hormone thyroid levels were an average of 5 percent higher in those with minor depression (average, 3.72 picograms per milliliter) and 33 percent higher in those with major depressive disorder (average, 4.69 picograms per milliliter) than in those who were not depressed (average, 3.53 picograms per milliliter).
The findings may be important to patients because both low blood vitamin D levels and high parathyroid hormone levels can be treated with higher dietary intake of vitamin D or calcium and increased sunlight exposure. "Moreover, the clinical relevance of the present study is underscored by our finding that 38.8 percent of men and 56.9 percent of women in our community-based cohort had an insufficient vitamin D status," they conclude. Additional studies are needed to determine whether changes in levels of vitamin D and parathyroid hormone precede depression or follow it.
Journal reference: Arch Gen Psychiatry. 2008;65[5]:508-512.
This study was supported by a clinical fellow grant from the Netherlands Organisation for Scientific Research. .
About 13 percent of older individuals have symptoms of depression, and other researchers have speculated that vitamin D may be linked to depression and other psychiatric illnesses, according to background information in the article. "Underlying causes of vitamin D deficiency such as less sun exposure as a result of decreased outdoor activity, different housing or clothing habits and decreased vitamin intake may be secondary to depression, but depression may also be the consequence of poor vitamin D status," the authors write. "Moreover, poor vitamin D status causes an increase in serum parathyroid hormone levels." Overactive parathyroid glands are frequently accompanied by symptoms of depression that disappear after treatment of the condition.
Witte J. G. Hoogendijk, M.D., Ph.D., and colleagues at VU University Medical Center, Vrije Universiteit Amsterdam, the Netherlands, measured blood levels of vitamin D and parathyroid hormone and assessed symptoms of depression among 1,282 community residents age 65 to 95. Of those individuals, 26 had a diagnosis of major depressive disorder, 169 had minor depression and 1,087 were not depressed. The average blood vitamin D level was 21 nanograms per milliliter and the average parathyroid hormone level was 3.6 picograms per milliliter.
Blood vitamin D levels were 14 percent lower in individuals with major and minor depression (average, 19 nanograms per milliliter) compared with non-depressed participants (average, 22 nanograms per milliliter). In addition, parathyroid hormone thyroid levels were an average of 5 percent higher in those with minor depression (average, 3.72 picograms per milliliter) and 33 percent higher in those with major depressive disorder (average, 4.69 picograms per milliliter) than in those who were not depressed (average, 3.53 picograms per milliliter).
The findings may be important to patients because both low blood vitamin D levels and high parathyroid hormone levels can be treated with higher dietary intake of vitamin D or calcium and increased sunlight exposure. "Moreover, the clinical relevance of the present study is underscored by our finding that 38.8 percent of men and 56.9 percent of women in our community-based cohort had an insufficient vitamin D status," they conclude. Additional studies are needed to determine whether changes in levels of vitamin D and parathyroid hormone precede depression or follow it.
Journal reference: Arch Gen Psychiatry. 2008;65[5]:508-512.
This study was supported by a clinical fellow grant from the Netherlands Organisation for Scientific Research. .
Folic Acid, B Vitamins Not Linked To Reduced Risk Of Cardiovascular Events In High-risk Women
Women at high-risk of cardiovascular disease who took a daily supplement of folic acid and vitamin B6 and B12 for seven years did not have an overall reduced rate of cardiovascular events, despite a significant lowering of homocysteine levels, according to a new study.
"Homocysteine [an amino acid produced by the body] levels have been directly associated with cardiovascular risk in observational studies; and daily supplementation with folic acid, vitamin B6, vitamin B12, or a combination have been shown to reduce homocysteine levels to varying degrees in intervention studies," the authors write. Observational data suggest cardiovascular benefits from B-vitamin supplementation may be greater among women, yet women have been underrepresented in published randomized trials. "Given the paucity of data on women and the known influences of estrogen on homocysteine levels, adequately powered randomized trials of homocysteine lowering in women are still needed."
Christine M. Albert, M.D., M.P.H., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues tested whether a combination of folic acid, vitamin B6 and vitamin B12 would reduce total cardiovascular events among women at high risk for the development of cardiovascular disease (CVD) over 7 years of follow-up. Within an ongoing randomized trial of antioxidant vitamins, 5,442 women who were U.S. health professionals age 42 years or older, with either a history of CVD or three or more coronary risk factors, were enrolled in a randomized trial to receive a combination pill containing folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) or a matching placebo.
During the 7.3 years of follow-up, 796 participants (14.6 percent) experienced a confirmed CVD event included in the primary end point (heart attack, stroke, coronary revascularization, or CVD death), with some individuals experiencing more than one event. There was no difference in the cumulative incidence of the primary combined end point in the active vs. placebo treatment groups at any time during study follow-up. A total of 406 women (14.9 percent) in the active treatment group and 390 (14.3 percent) in the placebo group experienced at least one cardiovascular event included in the primary end point.
When analyzed separately, there were no significant differences for each of the components of the primary outcome including heart attack, stroke, and CVD death, between the active treatment and placebo groups. Also, the risk of death from any cause was similar between the active and placebo treatment groups.
The researchers also found that the average plasma homocysteine level was 18.5 percent lower in the active group than that observed in the placebo group.
"Our results are consistent with prior randomized trials performed primarily among men with established vascular disease and do not support the use of folic acid and B vitamin supplements as preventive interventions for CVD in these high-risk fortified populations," the authors write.
Journal reference: JAMA. 2008;299[17]:2027-2036.
Editorial: Homocysteine-Lowering B Vitamin Therapy in Cardiovascular Prevention--Wrong Again?
In an accompanying editorial, Eva Lonn, M.D., M.Sc., F.R.C.P.C., of McMaster University, Hamilton, Ontario, Canada, comments on the findings of Albert and colleagues.
"... B vitamin supplements cannot currently be recommended for the prevention of CVD events (with the exception of rare genetic disorders) and there is no role for routine screening for elevated homocysteine levels. However, ongoing clinical research should provide further evidence on whether there may be any role for homocysteine-lowering B vitamin supplements in CVD prevention and for the overall importance of homocysteine as a CV risk factor."
"Homocysteine [an amino acid produced by the body] levels have been directly associated with cardiovascular risk in observational studies; and daily supplementation with folic acid, vitamin B6, vitamin B12, or a combination have been shown to reduce homocysteine levels to varying degrees in intervention studies," the authors write. Observational data suggest cardiovascular benefits from B-vitamin supplementation may be greater among women, yet women have been underrepresented in published randomized trials. "Given the paucity of data on women and the known influences of estrogen on homocysteine levels, adequately powered randomized trials of homocysteine lowering in women are still needed."
Christine M. Albert, M.D., M.P.H., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues tested whether a combination of folic acid, vitamin B6 and vitamin B12 would reduce total cardiovascular events among women at high risk for the development of cardiovascular disease (CVD) over 7 years of follow-up. Within an ongoing randomized trial of antioxidant vitamins, 5,442 women who were U.S. health professionals age 42 years or older, with either a history of CVD or three or more coronary risk factors, were enrolled in a randomized trial to receive a combination pill containing folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) or a matching placebo.
During the 7.3 years of follow-up, 796 participants (14.6 percent) experienced a confirmed CVD event included in the primary end point (heart attack, stroke, coronary revascularization, or CVD death), with some individuals experiencing more than one event. There was no difference in the cumulative incidence of the primary combined end point in the active vs. placebo treatment groups at any time during study follow-up. A total of 406 women (14.9 percent) in the active treatment group and 390 (14.3 percent) in the placebo group experienced at least one cardiovascular event included in the primary end point.
When analyzed separately, there were no significant differences for each of the components of the primary outcome including heart attack, stroke, and CVD death, between the active treatment and placebo groups. Also, the risk of death from any cause was similar between the active and placebo treatment groups.
The researchers also found that the average plasma homocysteine level was 18.5 percent lower in the active group than that observed in the placebo group.
"Our results are consistent with prior randomized trials performed primarily among men with established vascular disease and do not support the use of folic acid and B vitamin supplements as preventive interventions for CVD in these high-risk fortified populations," the authors write.
Journal reference: JAMA. 2008;299[17]:2027-2036.
Editorial: Homocysteine-Lowering B Vitamin Therapy in Cardiovascular Prevention--Wrong Again?
In an accompanying editorial, Eva Lonn, M.D., M.Sc., F.R.C.P.C., of McMaster University, Hamilton, Ontario, Canada, comments on the findings of Albert and colleagues.
"... B vitamin supplements cannot currently be recommended for the prevention of CVD events (with the exception of rare genetic disorders) and there is no role for routine screening for elevated homocysteine levels. However, ongoing clinical research should provide further evidence on whether there may be any role for homocysteine-lowering B vitamin supplements in CVD prevention and for the overall importance of homocysteine as a CV risk factor."
Vitamin D Linked To Reduced Mortality Rate In Chronic Kidney Disease
For patients with moderate to severe chronic kidney disease (CKD), treatment with activated vitamin D may reduce the risk of death by approximately one-fourth, suggests a study in the August Journal of the American Society of Nephrology.
Many patients with advanced CKD take the drug calcitriol, an oral form of activated vitamin D, to treat elevated levels of parathyroid hormone. "Although activated vitamin D is known to influence many biological processes, previous clinical knowledge is limited to its effect on parathyroid hormone levels," explains Dr. Bryan Kestenbaum of the University of Washington in Seattle, one of the study authors.
The study included 1,418 patients who had stage 3 to 4 CKD, which means moderately to severely reduced kidney function. All patients also had high parathyroid hormone levels (hyperparathyroidism), which can contribute to weakening of the bones in CKD. The researchers identified one group of patients who were being treated with calcitriol to lower their parathyroid hormone levels and another group who were not receiving calcitriol.
During a two-year follow-up period, mortality rates were compared for patients who were and were not taking calcitriol. "We then adjusted for differences in age, kidney function, parathyroid hormone levels, other illnesses, and other medications," says Dr. Kestenbaum.
In the adjusted analysis, the overall risk of death was about 26 percent lower for patients taking calcitriol. Patients on calcitriol were also less likely to develop end-stage renal disease, requiring dialysis to replace lost kidney function.
Overall, treatment with calcitriol was associated with a 20 percent reduction in the risk of either death or dialysis. The reduction in mortality with calcitriol was unrelated to its effect on parathyroid hormone levels.
"Recently, there has been an increased focus on the effects of vitamin D beyond those on bone health," Dr. Kestenbaum comments. "Vitamin D deficiency has been associated with risk factors for cardiovascular disease, such as high blood pressure, diabetes, and inflammation." Previous studies have suggested that treatment with intravenous vitamin D can improve survival in patients on hemodialysis.
The new results suggest that treatment with oral activated vitamin D may also improve survival in patients with CKD who do not yet require dialysis. "Randomized clinical trials are needed to test the hypothesis that vitamin D therapy can improve cardiovascular health and survival in CKD," Dr. Kestenbaum adds. "Future studies should also examine the role of non-activated vitamin D, which is less expensive and less toxic."
The study has some important limitations, including a lack of data on other factors that may have affected survival in patients taking calcitriol. Also, since the study included mainly older, white men, the results may not apply to younger, more ethnically diverse populations with CKD.
Many patients with advanced CKD take the drug calcitriol, an oral form of activated vitamin D, to treat elevated levels of parathyroid hormone. "Although activated vitamin D is known to influence many biological processes, previous clinical knowledge is limited to its effect on parathyroid hormone levels," explains Dr. Bryan Kestenbaum of the University of Washington in Seattle, one of the study authors.
The study included 1,418 patients who had stage 3 to 4 CKD, which means moderately to severely reduced kidney function. All patients also had high parathyroid hormone levels (hyperparathyroidism), which can contribute to weakening of the bones in CKD. The researchers identified one group of patients who were being treated with calcitriol to lower their parathyroid hormone levels and another group who were not receiving calcitriol.
During a two-year follow-up period, mortality rates were compared for patients who were and were not taking calcitriol. "We then adjusted for differences in age, kidney function, parathyroid hormone levels, other illnesses, and other medications," says Dr. Kestenbaum.
In the adjusted analysis, the overall risk of death was about 26 percent lower for patients taking calcitriol. Patients on calcitriol were also less likely to develop end-stage renal disease, requiring dialysis to replace lost kidney function.
Overall, treatment with calcitriol was associated with a 20 percent reduction in the risk of either death or dialysis. The reduction in mortality with calcitriol was unrelated to its effect on parathyroid hormone levels.
"Recently, there has been an increased focus on the effects of vitamin D beyond those on bone health," Dr. Kestenbaum comments. "Vitamin D deficiency has been associated with risk factors for cardiovascular disease, such as high blood pressure, diabetes, and inflammation." Previous studies have suggested that treatment with intravenous vitamin D can improve survival in patients on hemodialysis.
The new results suggest that treatment with oral activated vitamin D may also improve survival in patients with CKD who do not yet require dialysis. "Randomized clinical trials are needed to test the hypothesis that vitamin D therapy can improve cardiovascular health and survival in CKD," Dr. Kestenbaum adds. "Future studies should also examine the role of non-activated vitamin D, which is less expensive and less toxic."
The study has some important limitations, including a lack of data on other factors that may have affected survival in patients taking calcitriol. Also, since the study included mainly older, white men, the results may not apply to younger, more ethnically diverse populations with CKD.
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