Two studies released this week reach contradictory conclusions on the value of B vitamins and folic acid (or folate in its naturally occurring form) in reducing the risks of heart disease. What are doctors and their patients to make of this?
"Not much," says Dr. Steven Woloshin of Dartmouth University's Institute for Health Policy and Clinical Practice.
"One study is very weak and the conclusions can't be believed and the other's results don't add much for practitioners or their patients," Woloshin told Reuters Health.
In the first study, Japanese researchers wanted to know if folate and vitamins B6 and B12 in the diet would have any affect on deaths due to heart disease.
Foods that are rich in B vitamins and folate include beans, lentils, potatoes, peanuts, spinach, broccoli, brussel sprouts, and some fruits such as bananas, strawberries, and oranges.
Using data from the large observational Japan Collaborative Cohort Study, Dr. Renzhe Cui and colleagues calculated the nutrients eaten daily by 23,119 men and 35,611 women by analyzing their answers given in food "frequency" questionnaires.
After 14 years of follow-up, 3815 deaths related to heart disease were recorded in the study population of 58,730: 986 from stroke, 424 from coronary heart disease, 318 from heart failure, and 2087 from cardiovascular disease.
In a nutshell, the results suggested that eating a diet high in folate and vitamin B6 was associated with reduced risk of death from heart failure in men and with reduced risk of death from stroke, coronary heart disease, and cardiovascular disease in women.
In the American Heart Association's journal Stroke, the researchers conclude that greater folate and vitamin B6 in the diet may be useful in preventing cardiovascular disease.
Woloshin questions the validity of such a claim, because of the study's design. The researchers can't tell from the data what factors may be responsible for the observed differences, Woloshin said: "There's nothing to hang your hat on."
"For instance, women were more likely to smoke if they ate less folate. Maybe they have other less healthy habits and that's why they are more likely to die of heart failure," Woloshin said. The data gathered in the observational study doesn't say.
A randomized controlled trial, such as the study by the other research group, is needed to make such claims, he said.
Researchers at the University of Bergen in Norway looked at data gathered in the Western Norway B Vitamin Intervention Trial, which included 3,090 patients suspected of having coronary artery disease.
Participants had angiograms to look at restricted blood flow in the coronary arteries. Blood was also collected to measure levels of an enzyme, homocysteine. High blood levels of homocysteine have been associated with increased risk of heart disease.
Study subjects were randomly assigned to take one of three supplement formulations of folic acid, B6 and B12, or a placebo. One hundred eighty-three patients, with a total of 309 lesions in their coronary arteries, were included in this study's analysis. After 10 months, blood was tested, follow-up angiograms were performed and blockages measured again.
Even though homocysteine in the blood was reduced an average of 22 percent in the patients who got a folic acid/B12 supplement, "overall disease progression was not affected," the researchers found.
Writing in the American Journal of Cardiology, Kjetil Loland and colleagues reported detecting "no statistically significant results from treatment." Coronary artery disease had progressed unabated, they note. In fact in one subgroup, CAD appeared to progress more rapidly for those getting the supplement.
"It must be noted that this was in a post-hoc analysis of a subgroup of patient. We felt however obliged to report this finding," Loland told Reuters Health in an email.
Otherwise, "the results support a growing amount of evidence that B-vitamin treatment of cardiovascular disease is ineffective" in patients with established cardiovascular disease," Loland added.
The results also suggest, Loland said, that high homocysteine levels are not a cause of heart disease and treatments aimed at reducing them won't reduce the heart disease risk itself.
Loland said that by using two measurements of arterial blockage, he and his colleagues were, for the first time, able to look at "clinically silent disease progression."
Woloshin believes significant research now has settled the question of whether folic acid and B vitamin supplementation help reduce the risks of heart disease. "It doesn't," he said.
SOURCE: Stroke, April, 2010. American Journal of Cardiology, April 2010
Friday, July 9, 2010
Thursday, November 19, 2009
Scientists Identify Two Gene Variants Associated with Alzheimer's Risk
In the largest genome-wide association study (GWAS) reported to date involving Alzheimer's disease, scientists have identified two new possible genetic risk factors for late-onset Alzheimer's, the most common form of the disease. The study, which pooled DNA samples from a number of European and U.S. groups, not only associated variations in the sequence of the CLU and PICALM genes with increased risk, but also found another 13 gene variants that merit further investigation, according to findings presented in the September 6, 2009, online issue of Nature Genetics. Involving more than 16,000 DNA samples, one feature of this research was its use of publicly shared DNA samples and databases, including several supported by the National Institute on Aging (NIA) and other components of the National Institutes of Health.
To date, only four genes have been definitively associated with Alzheimer's disease. Three mutated genes — amyloid precursor protein (APP) and the presenilins (PS1 and PS2) — have been shown to cause the rare, early-onset familial form of the disease, which mostly occurs in middle age. Only one gene variant, apolipoprotein e4 or APO-e4, has been confirmed as a significant risk factor gene for the common form of late-onset Alzheimer's, which typically strikes after age 65. GWAS studies look for genetic associations with a disease in the DNA on all of the chromosomes in a specific population of individuals. To date, such studies have been done on relatively small numbers of samples and have not been able to identify genetic variations of smaller effect. But now, GWAS studies in very large sample sets are able to identify these elusive genetic variations.
"GWAS research is entering a new phase of discovery, with much larger sample sizes made available for analysis due to highly collaborative researchers and rapid DNA sample and data sharing," said Marcelle Morrison-Bogorad, Ph.D., director of the NIA Division of Neuroscience. "Identifying gene variants like CLU and PICALM advances our understanding of the many genetic factors that may contribute to overall risk for this devastating neurological disorder and how these genes affect the development of Alzheimer's. This knowledge may then lead to novel disease pathways that can be targeted to develop new treatments."
The collaborative consortium led by Julie Williams, Ph.D., and her colleagues at the School of Medicine at Cardiff University, Wales, used brain and blood tissues made available and analyzed by dozens of laboratories in the United Kingdom, Ireland, Germany, Belgium, Greece and the United States. The two-stage study first used samples from people with Alzheimer’s and a control group free of the disease to locate CLU on chromosome 8 and PICALM on chromosome 11, and then replicated the findings in a second stage of testing.
CLU (ApoJ/clusterin located on chromosome 8) and PICALM (phosphatidylinositol-binding clathrin assembly protein located on chromosome 11) are both potentially involved in important pathways involved in AD. While more study is needed to determine the roles of the CLU and PICALM variants in Alzheimer’s pathology, the researchers noted that CLU levels are often elevated when brain tissue is injured or inflamed. Increased levels of CLU are found in the brains and cerebrospinal fluids of Alzheimer's patients. Neurons have trouble functioning in neurodegenerative diseases because as the disease progresses, the connections between neurons, or synapses, often break down. Senile plaques and associated beta-amyloid are another hallmark of Alzheimer's disease. Geneticists hypothesize that PICALM may play a role in synaptic health and that it may also affect the levels of beta-amyloid deposits in the brain.
The U.S. laboratories contributing samples to the study were: NIA's Laboratory of Neurogenetics, Bethesda, Md., and NIA-funded scientists at Washington University School of Medicine, St. Louis; Mayo Clinic College of Medicine, Jacksonville, Fla.; and Mayo Clinic and Mayo Foundation, Rochester, Minn. Samples were also provided by institutions supported by other NIH components, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Human Genome Research Institute, the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
To date, only four genes have been definitively associated with Alzheimer's disease. Three mutated genes — amyloid precursor protein (APP) and the presenilins (PS1 and PS2) — have been shown to cause the rare, early-onset familial form of the disease, which mostly occurs in middle age. Only one gene variant, apolipoprotein e4 or APO-e4, has been confirmed as a significant risk factor gene for the common form of late-onset Alzheimer's, which typically strikes after age 65. GWAS studies look for genetic associations with a disease in the DNA on all of the chromosomes in a specific population of individuals. To date, such studies have been done on relatively small numbers of samples and have not been able to identify genetic variations of smaller effect. But now, GWAS studies in very large sample sets are able to identify these elusive genetic variations.
"GWAS research is entering a new phase of discovery, with much larger sample sizes made available for analysis due to highly collaborative researchers and rapid DNA sample and data sharing," said Marcelle Morrison-Bogorad, Ph.D., director of the NIA Division of Neuroscience. "Identifying gene variants like CLU and PICALM advances our understanding of the many genetic factors that may contribute to overall risk for this devastating neurological disorder and how these genes affect the development of Alzheimer's. This knowledge may then lead to novel disease pathways that can be targeted to develop new treatments."
The collaborative consortium led by Julie Williams, Ph.D., and her colleagues at the School of Medicine at Cardiff University, Wales, used brain and blood tissues made available and analyzed by dozens of laboratories in the United Kingdom, Ireland, Germany, Belgium, Greece and the United States. The two-stage study first used samples from people with Alzheimer’s and a control group free of the disease to locate CLU on chromosome 8 and PICALM on chromosome 11, and then replicated the findings in a second stage of testing.
CLU (ApoJ/clusterin located on chromosome 8) and PICALM (phosphatidylinositol-binding clathrin assembly protein located on chromosome 11) are both potentially involved in important pathways involved in AD. While more study is needed to determine the roles of the CLU and PICALM variants in Alzheimer’s pathology, the researchers noted that CLU levels are often elevated when brain tissue is injured or inflamed. Increased levels of CLU are found in the brains and cerebrospinal fluids of Alzheimer's patients. Neurons have trouble functioning in neurodegenerative diseases because as the disease progresses, the connections between neurons, or synapses, often break down. Senile plaques and associated beta-amyloid are another hallmark of Alzheimer's disease. Geneticists hypothesize that PICALM may play a role in synaptic health and that it may also affect the levels of beta-amyloid deposits in the brain.
The U.S. laboratories contributing samples to the study were: NIA's Laboratory of Neurogenetics, Bethesda, Md., and NIA-funded scientists at Washington University School of Medicine, St. Louis; Mayo Clinic College of Medicine, Jacksonville, Fla.; and Mayo Clinic and Mayo Foundation, Rochester, Minn. Samples were also provided by institutions supported by other NIH components, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Human Genome Research Institute, the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Sunday, October 11, 2009
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