Omega-3 fatty acid balance influences depression risk
A report scheduled to be published online in the journal Psychosomatic Medicine concluded that Americans need to improve their ratio of omega-6 to omega-3 fatty acids if we want to reduce depression and inflammatory diseases.
Ohio State University professor of psychiatry and psychology Jan Kiecolt-Glaser and colleagues studied 43 middle-aged to elderly men and women, of whom nearly half were the caregivers of spouses with Alzheimer's disease or other dementias, which is known to confer a significant amount of stress. The participants' blood was analyzed for interleukin-6 (IL-6), tumor necrosis factor -alpha (TNF-alpha) and the receptor molecule for IL-6, all involved in inflammation. Completed questionnaires provided information on diet and depression levels.
It was found that participants who consumed more omega-6 compared to omega-3 fatty acids and who reported more symptoms of depression had significantly higher levels of the inflammatory cytokines IL-6 and TNF-alpha.
"In this study, we're looking at the intersection of behavior, immune function and diet. In past experiments, we concentrated only on the first two," Dr Kiecolt-Glaser commented. "It now appears that diet is a very important variable in the equation as to how people respond to depression and stress."
"The data suggest that higher depression and a poorer diet in terms of omega-3 can work together to promote inflammation. Other researchers have shown that clinically depressed people -- those with more severe depression -- often have lower omega-3 levels in their blood, and several studies have shown that supplementing diets with omega-3 improves depression," he noted. "People who are depressed don't eat well, or it might be that there is something about depression that affects how well people process such foods."
Coauthor Martha Belury added, "The important message for consumers is that they don't have to take mega-doses of omega-3 to have some impact."
Proanthocyanidins help prevent skin cancer
A one-day symposium held on March 25, 2007 during the 233rd national meeting of the American Chemical Society in Chicago was the site of a presentation by associate professor Santosh Katiyar, PhD, of the University of Alabama at Birmingham department of dermatology concerning the finding that proanthocyanidins from grape seeds help prevent ultraviolet light-induced skin cancer by improving the immune system.
Hairless mice were given diets supplemented with a high or low percentage of grape seed proanthocyanidins, or a control diet and exposed to ultraviolet B (UVB) light. Mice that received proanthocyanidins experienced a reduction in tumor incidence, as well as fewer and smaller tumors compared with animals provided with an unenhanced diet.
Because immune suppression caused by ultraviolet-B radiation has been implicated in skin cancer risk, the research team investigated whether grapeseed proanthocyanidins affected UVB's effect on immune function. They found that the compound inhibited ultraviolet-B induced suppression of contact hypersensitivity in mice. Administration of proanthocyanidins reduced the increase in an immunosuppressive cytokine known as interleukin-10 in skin exposed to ultraviolet-B and in draining lymph notes compared with animals that did not receive the compound, while enhancing the production of immunostimulatory cytokine interleukin-12 (IL-12) in lymph nodes. Mice injected with an antibody that neutralized IL-12 did not experience the protective effects of proanthocyanidins against UVB induced immune suppression. "Our data suggested that prevention of photocarcinogenesis by grape seed proanthocyanidins is mediated through development of anti-tumor immune responses, which are regulated by IL-12 induction in mice," the authors conclude.
"Grape seed proanthocyanidins also have antioxidant properties, and UV-induced oxidative stress has been implicated in the induction of skin cancers," Dr Katiyar added. "We speculate that the use of grape seed proanthocyanidins as a dietary supplement may have beneficial effects in protecting cutaneous disorders in UV-exposed skin including the risk of skin cancers."
Blueberries may help prevent colon cancer
On March 25, 2007, the 233rd national meeting of the American Chemical Society was the site of a presentation by Bandaru S. Reddy, PhD, of Rutgers University in Piscataway, New Jersey, of the discovery that a compound occurring in blueberries helps protect laboratory animals from developing colon cancer. The compound, known as pterostilbene, is an antioxidant similar to resveratrol that could be developed into a preventive nutritional supplement.
Dr Reddy and his colleagues gave the carcinogen azoxymethane to eighteen rats to induce colon cancer. The rats were provided with balanced diets, half of which were supplemented with pterostilbene. After eight weeks, animals that received the compound had 57 percent fewer precancerous colon lesions than the control rats as well as reduced colon cell proliferation. Rats that consumed pterostilbene also experienced a reduction in the expression of genes involved in inflammation, which is a risk factor for the disease. Dr Reddy noted that some research suggests that pterostilbene may lower lipids, which, when elevated, are another known risk factor for colon cancer. A study conducted by coauthor Agnes Rimando of the USDA, also presented at the American Chemical Society's meeting, revealed that blueberry skins reduce cholesterol in animals when added to their diets.
Dr Reddy suggested that pterostilbene could be combined with COX-2 inhibitors, which are anti-inflammatory drugs that have demonstrated a preventive effect against colon cancer in laboratory animals. By adding pterostilbene, the drugs could be administered in lower doses, which would reduce some of their well-known side effects.
The research, funded by the National Institutes of Health, is the first to demonstrate the ability of pterostilbene to combat colon cancer. “This study underscores the need to include more berries in the diet, especially blueberries,” Dr Reddy stated.
Low dose DHA reduces diastolic blood pressure
A report published in the April, 2007 issue of The Journal of Nutrition concludes that supplementing with a low dose of docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid found in fish and the algae they feed on, lowers diastolic blood pressure in middle-aged men and women.
Thomas A. B. Sanders of King's College London and his British colleagues randomized 20 men and 18 women aged 40 to 65 to receive 0.7 grams DHA derived from algae or an olive oil placebo daily for three months. The treatment period was followed by an intervening period of at least four months during which no supplement was given, succeeded by another three months during which each group was given the supplement the other group had received in the initial treatment phase. Blood pressure was measured, and blood and urine samples were collected and tested at the beginning and end of each treatment period.
Treatment with DHA resulted in a 58 percent increase in the DHA content of red blood cells, accompanied by a reduction in the proportions of omega-6 fatty acids. Although measures of arterial stiffness and endothelial function did not change during the short periods of DHA administration, diastolic blood pressure was lowered by an average of 3.3. mm HG and heart rate was reduced by 2.1 beats per minute after DHA administration compared to after the placebo period.
"A significant reduction in diastolic blood pressure was noted which is likely to be of clinical significance with regard to risk of future vascular events in middle-aged subjects," the authors conclude. "Future work is needed to confirm these findings and to investigate further the effects of DHA on cardiac function.
High lignan diet linked with lower risk of breast cancer
The March 21, 2007 issue of the Journal of the National Cancer Institute published the results of a large prospective study of postmenopausal women which concluded that women who consume high levels of lignans may have a reduced risk of breast cancer. Lignans are estrogen-like compounds found in such plant foods as flaxseed in addition to some fruits, vegetables, and whole grains. Because phytoestrogens can bind to estrogen receptors, they may be involved in the prevention of breast cancer.
The current study included 58,049 postmenopausal women living in France. Marina Touillaud, PhD of the National Institute of Health and Medical Research in France, and colleagues analyzed the results of dietary questionnaires completed by the participants to determine their intake of the plant lignans pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol, and estimated the exposure to two enterolignans metabolized from plant lignans by intestinal bacteria. The participants were followed for a median of 7.7 years, during which 1,469 women developed breast cancer.
Women whose intake of lignans was in the top 25 percent of participants were found to have a 17 percent lower risk of breast cancer than those whose intake was in the lowest fourth. When the individual lignans were analyzed, lariciersinol was found to be associated with a similar benefit. The protective effect was limited to cancers that were estrogen and progesterone receptor positive. High total estimated enterolignan levels were also associated with protection.
"Although the possible role of plant foods in breast cancer prevention is still debated, increasing dietary lignan intake may be an interesting potential preventative approach," the authors write. "In view of the epidemiologic results of this study, the recommendation that women should consume diets that consist largely of fruits, vegetables, and cereals—all foods rich in lignans—should continue."
Inflammation may be involved in prostate cancer metastasis
A report published online on March 19, 2007 in the journal Nature described the findings of University of California San Diego researchers that the inflammation associated with the immune system's attack on prostate tumors could be involved in their metastasis. It has been hypothesized that genetic changes within the cancer cell result in metastasis, but this does not explain metastases that occur years after the primary tumor.
Working with a mouse model of prostate cancer, professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, Michael Karin, PhD, and his colleagues discovered a signaling pathway that increased prostate tumor metastases. They found that a cytokine called RANK ligand, produced by inflammatory cells, initiates a chain reaction in which a protein kinase known as IKKa is activated to enter the cancer cell nucleus and reduce the expression of the antimetastatic gene Maspin.
"An excellent inverse correlation between IKKa activation and Maspin production was detected, such that advanced prostate cancer cells contain high amounts of activated IKKa in their nuclei and express little or no Maspin," Dr Karin stated. "Maspin is a very potent inhibitor of metastasis; in a patient with metastasis, cells have found a way to turn off Maspin, which may depend on invasion of the tumor with RANK ligand-producing cells that activate IKKa."
"Our findings suggest that promoting inflammation of the cancerous tissue, for instance, by performing prostate biopsies, may, ironically, hasten progression of metastasis," Dr Karin observed. "We have shown that proteins produced by inflammatory cells are the 'smoking gun' behind prostate cancer metastasis. The next step is to completely indict one of them."
Research team member Steven L. Gonias, MD, PhD, added, "This study helps explain the paradox that, in certain types of malignancy, inflammation within a cancer may be counterproductive."
Meta-analysis concludes aspirin helps prevent colorectal cancer
The results of a meta-analysis published in the March 6, 2007 issue of the Annals of Internal Medicine found that regular users of aspirin have a lower rate of colon polyps (adenoma) and colorectal cancer than nonusers.
Canadian reviewers identified 17 studies which sought to determine the preventive effect of aspirin on colorectal cancer, 14 that investigated the drug's effect on colorectal adenoma (which are a precursor of cancer), and 12 reviews of the drug's potential harm. Analysis of cohort studies (which examine a particular population of individuals) determined that regular use of aspirin reduced the risk of colorectal cancer by 22 percent compared with nonusers. One large, long-term study of American women showed that higher doses or the use of aspirin for ten years or more further lowered risk.
For polyps, randomized clinical trials found an 18 percent reduction associated with aspirin use. For case-control studies (which compare individuals with a condition to matched control subjects who do not have the condition), there was a 13 percent lower risk, and in cohort studies there was a 28 percent reduction for aspirin users compared with nonusers.
While primary prevention trials of aspirin did not find a higher rate of stroke associated with aspirin use, secondary prevention trials using higher doses of aspirin found an increase in hemorrhagic stroke risk, while the risk of ischemic stroke decreased. Increased gastrointestinal complications were also associated with aspirin use.
"In conclusion, aspirin appears to reduce the incidence of colorectal adenomas and colorectal cancer," the authors write. "The available data would suggest that for chemoprevention, aspirin would need to be used in doses greater than used for cardiovascular prevention and for a duration close to 10 years. Therefore, the potential benefit of aspirin chemoprevention would need to be carefully weighed against its harms."
High "normal" glucose levels predict congestive heart failure hospitalization
Blood glucose levels falling in the high end of the normal range or greater are associated with an increased risk of hospitalization for congestive heart failure among heart attack patients and others at risk of developing heart failure, according to a report published online on March 5, 2007 in Circulation: Journal of the American Heart Association. Heart failure occurs when the heart cannot pump an adequate supply of blood throughout the body. Risk factors other than heart attack are diabetes and uncontrolled high blood pressure.
Associate professor of cardiology at the Karolinska Institutet Claes Held, MD, PhD, and colleagues evaluated data from 31,546 high-risk patients participating in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND). Subjects were classified as having low-normal glucose, high-normal glucose, impaired fasting glucose, newly diagnosed diabetes, or previously diagnosed diabetes upon enrollment.
During an average 2.4 year follow up there were 668 hospitalizations for congestive heart failure. It was discovered that even small elevations in fasting glucose increased the risk of developing congestive heart failure in both diabetic and nondiabetic patients.
“Even in the normal range, our results indicate that elevated blood glucose is associated with the risk of heart failure." Dr Held stated. "You can look at blood glucose much like blood pressure or cholesterol. Even if you have normal blood glucose, there is a gradual increase in risk wherever you start on the scale. If the blood sugar is 'high normal' there is a higher risk than those with 'low normal fasting blood glucose levels.'"
The authors conclude that their findings "are consistent with accumulating evidence showing that elevated glucose is a progressive risk factor for cardiovascular disease outcomes even with levels below the threshold for a diagnosis of diabetes mellitus."
A new vitamin?
The March 12, 2007 issue of Chemistry & Industry, published an article by Marina Murphy that unveils glowing expectations for epicatechin, a compound found in cocoa, tea and wine. In fact, Harvard Medical School professor of medicine Norman Hollenberg believes that the compound is so important that it should be considered a vitamin.
Dr Hollenberg's observations of the Kuna people of Panama, who drink up to 40 cups of cocoa per week, are the source of his enthusiasm. The risk of the some of the most common western diseases: stroke, heart failure, cancer and diabetes, is reduced to less than 10 percent in this population. Additionally, no dementia has been observed among their many long-lived individuals. "If these observations predict the future, then we can say without blushing that they are among the most important observations in the history of medicine," Dr Hollenberg stated. "We all agree that penicillin and anesthesia are enormously important. But epicatechin could potentially get rid of 4 of the 5 most common diseases in the western world, how important does that make epicatechin?... I would say very important."
Natural Products Association vice president of scientific affairs Daniel Fabricant shares Dr Hollenberg's views. "Vitamins are defined as being essential to the normal functioning, metabolism, regulation and growth of cells," he explained. "At the moment, the science does not support epicatechin having an essential role." However, he noted that "the link between high epicatechin consumption and a decreased risk of killer disease is so striking, it should be investigated further. It may be that these diseases are the result of epicatechin deficiency."
For now, Fabricant suggests that phytonutrient is a more appropriate term since it is not yet known whether the compound is essential.
While many individuals might look forward to a guilt-free mug of hot chocolate, "no doubt some people would prefer to get their epicatechin in capsule form," Dr Hollenberg noted.
The heart needs copper
Although too much copper can be problematic health-wise, researchers at the University of Louisville in Kentucky and the USDA Human Nutrition Research Center reported online on the March 5, 2007 in The Journal of Experimental Medicine that supplementing mice with the mineral prevents enlargement of the heart when the organ is stressed. Deficient copper intake has been associated with increased cholesterol levels, clot formation, and heart disease.
Y. James Kang and colleagues at the University of Louisville School of Medicine used a mouse model of hypertrophic cardiomyopathy caused by pressure overload induced by constriction of the ascending aorta. A group of control mice received sham surgeries. The animals received a diet providing RDA adequate levels (6 milligrams per kilogram diet) of copper for eight weeks. After four weeks on the diet, some of the animals were changed to a diet providing higher levels (20 milligrams per kilogram diet) for the remaining four weeks.
Four weeks after the surgery, cardiac hypertrophy (enlargement) was observed. This was significantly reversed during the final four weeks of the study in the animals who received the higher copper diet, while the remainder went on to develop heart failure. The researchers found that supplementing with copper promoted the synthesis of vascular endothelial growth factor (VEGF), a protein that increases the growth of new blood vessels, which was reduced in the late phase of cardiac hypertrophy among mice that did not receive extra copper.
The human equivalent dose for the high dose of copper used in the study is 2.9 milligrams per day, however, the recommended daily intake is only 0.9 milligrams. "Should similar effects of copper supplementation be found in controlled studies in human patients," the authors write, "this will point the way to a simple, nontoxic and extraordinarily economical therapy for hypertrophic cardiomyopathy."
Omega-3 fatty acids boost gray matter, mood
On March 7, 2007 at the American Psychosomatic Society’s Annual Meeting held in Budapest, Hungary, Sarah M. Conklin, PhD of the University of Pittsburgh reported the discovery that an increased intake of omega-3 fatty acids is associated with greater gray matter volume in areas of the brain related to mood and behavior.
Animal research has shown that increasing omega-3 fatty acids in the diet results in structural brain changes. The researchers involved in the current study sought to determine whether gray matter volume was related to omega-3 fatty acid intake in humans to help explain the improvement in mood associated with increased omega-3 intake.
Dr Conklin, who is a postdoctoral scholar at the Cardiovascular Behavioral Medicine Program in the department of psychiatry at the University of Pittsburgh, and her colleagues questioned 55 healthy adults on their diets to determine their average intake of long-chain omega-3 fatty acids. High-resolution structural magnetic resonance imaging (MRI) of the brain was used to measure gray matter volume.
It was discovered that subjects whose intake of omega-3 fatty acids was high had greater gray matter volume in the bilateral anterior cingulate cortex, the right amygdala and the right hippocampus, which are associated with with emotional arousal and regulation. These areas have been found to be reduced in individuals with mood disorders such as major depressive disorder.
In a study presented by Dr. Conklin at the previous year's meeting, researchers at the University of Pittsburgh found that participants who had lower blood levels of omega-3 fatty acids tended to have a more negative outlook and were more impulsive.
Although the current study found an association with structural changes in the brain associated with greater omega-3 fatty acid intake, the team recommends further research to confirm a causative effect.
Whole grain breakfasts lower heart failure risk
The American Heart Association’s 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention was the site of a presentation on March 2, 2007 by Luc Djoussé, MD, MPH of Harvard Medical School of the finding that eating a whole-grain breakfast reduces the risk of developing heart failure.
Dr Djoussé's team analyzed data from 1982 to 2006 obtained in the Physicians’ Health Study for the current research. In questionnaires completed at the beginning of the study, 79 percent of 10,469 physicians reported consuming breakfast cereals that contained at least 25 percent oat or bran.
Among the 35 percent of participants who reported consuming the cereals at least seven times per week, the risk of heart failure was reduced by 28 percent over the course of the study compared to participants who reported never eating them. A 22 percent risk reduction was observed among 39 percent subjects who consumed the cereals two to six times per week, and among the 26 percent who reported eating them up to once per week , there was a 14 percent reduction. When possible changes in cereal intake over time were taken into consideration, the results remained unchanged.
Dr Djoussé, who is assistant professor of medicine in the Division of Aging at Brigham & Women’s Hospital and Harvard Medical School, observed, "There are good and powerful arguments for eating a whole-grain cereal for breakfast. The significant health benefits of whole-grain cereal are not just for kids, but also for adults. A whole-grain, high-fiber breakfast may lower blood pressure and bad cholesterol and prevent heart attacks."
"The Physicians’ Health Study shows that even in a population with overall healthy behavior, it is possible to see less heart failure in those who eat a whole-grain cereal breakfast," he added.