Melatonin slows signs of aging in mice
Research conducted by The Spanish Ageing Research Network, headed by Dario Acuna Castroviejo of the University of Granada in Spain, has found that orally administered melatonin can help delay the effects of aging in mice.
Dr Acuna Castroviejo, of the University of Granada's Institute of Biotechnology, and his colleagues gave mice genetically engineered to age more rapidly as well as normal mice small amounts of melatonin beginning at five months of age when the animals begin to stop producing adequate levels of the hormone.
" We proved that the first signs of ageing in animal tissues start at the age of five months [in mice] – equivalent to 30 human years of age – due to an increase in free radicals (oxygen and nitrogen), which cause an inflammatory reaction,” explained Dr Acuna Castroviejo, who has coauthored a number of studies on melatonin and aging published in the Journal of Pineal Research.
It was discovered that melatonin neutralized aging-associated oxidative stress and inflammation, and delayed their effects. The researchers hope that the finding will be applicable to humans, and aid in the prevention of age-related diseases such as diabetes and Parkinson's disease.
Melatonin is found in small quantities in onions, cherries, bananas, corn, oats, rice, mint, lemon verbena, sage, thyme, and red wine. While melatonin is widely available in the United States as an over the counter nutritional supplement, Dr Acuna Castroviejo noted that melatonin is not currently approved by the Spanish Ministry of Health. "While the substance becomes legalised, humans should try to increase melatonin consumption through food," he recommends.
Older adults with inadequate vitamin D levels may risk disability
The April, 2007 issue of the Journal of Gerontology: Medical Sciences published the finding of researchers at Wake Forest University School of Medicine that older individuals who have low blood levels of vitamin D increase their risk of impaired physical performance and disability. Deficient levels of the vitamin occur in approximately one quarter of those over the age of 60.
Denise Houston, PhD and colleagues analyzed data from the InCHIANTI study, which evaluated factors contributing to late life loss of mobility. The study included 976 participants aged 65 and older. Physical performance was assessed by testing walking speed, ability to stand from a seated position, and ability to maintain balance in progressively more challenging positions. Handgrip strength, a predictor of future disability, was also measured.
Among subjects with low vitamin D levels, physical performance and grip strength were five to 10 percent lower than that of participants who did not have reduced levels. The finding remained valid after taking into consideration other factors such as season of the year and physical activity levels.
"With a growing older population, we need to identify better ways to reduce the risk of disability," Dr Houston stated. "Our study showed a significant relationship between low vitamin D levels in older adults and poorer physical performance."
"Recent findings showing the importance of vitamin D status on multiple health outcomes underscore the need for more research on the effects of low vitamin D levels in elderly populations," she concluded. "Higher amounts of vitamin D may be needed for the preservation of muscle strength and physical function as well as other conditions such as cancer prevention. The current recommendations are based primarily on vitamin D's effects on bone health."
Meta-analysis finds antioxidant supplementation safe during cancer therapy
The January/February and March/April 2007 issues of the journal Alternative Therapies published a two part article by a team at the Simone Protective Cancer Institute in Lawrenceville, New Jersey, which concluded that, contrary to long-held beliefs, antioxidant and other nutritional supplementation during chemotherapy or radiation does not interfere with these treatments.
"A single, front-page interview in The New York Times in 1997, which was not based on published scientific work, and a single research paper involving mice, along with a press release by its author in 1999, led to the erroneous notion that vitamin C interferes with chemotherapy and radiation in humans," the authors write. "This notion soon applied to all antioxidants as physicians, patients, the media, the American Cancer Society, and scores of websites took the same position without reviewing the scientific evidence."
For their meta-analysis, oncologist Charles B. Simone, MD, and colleagues identified 50 human studies that included a total of 8,251 participants involving the use of chemotherapy and/or radiation concurrently with dietary supplements. They discovered that antioxidants and other supplements failed to interfere with the treatments and were actually found to enhance them. In 47 of these studies, supplements were associated with protection of normal tissue and a reduction of side effects, and in 15 studies, 3,738 subjects experienced increased survival.
The authors explain that, due to a loss of the homeostasis control mechanism for the uptake of antioxidants, cancer cells accumulate large amounts of the nutrients, while healthy cells do not have this membrane defect. This accumulation decreases the oxidative reactions needed for the generation of the cells' energy. Additionally, the nutrients elicit other effects on cancer cells unrelated to their antioxidant activity.
The authors concluded that "Antioxidant and other nutrient food supplements are safe and can help to enhance cancer patient care."
Vegetable compound fights prostate cancer in two ways
The annual meeting of the American Association for Cancer Research was the site of a presentation on April 17, 2007 by Shivendra Singh, PhD of the University of Pittsburgh concerning his team's finding that isothiocyanates derived from cruciferous vegetables provide a two-pronged approach in slowing prostate cancer growth. The cruciferous family of vegetables, which includes broccoli, cauliflower, and cabbage, have demonstrated anticancer effects in a number of studies conducted over the past few decades. Phytochemicals known as isothiocyanates that are formed when the vegetables are cut or chewed may be responsible for some of these benefits.
Earlier research conducted by Dr Singh discovered a reduction in the growth of human prostate tumors implanted in mice that received a small amount of phenethyl-isothiocyanate (PEITC) for 31 days compared to animals that did not receive the compound. In the current study, Dr Singh's team found an inhibition of angiogenesis (the formation of new blood vessels that allows tumors to grow and spread) in cultured cells treated with PEITC.
Dr Singh, who is a professor of pharmacology and urology at the University of Pittsburgh School of Medicine, stated, "The contribution of diet and nutrition to cancer risk, prevention and treatment has been a major focus of research in recent years because certain nutrients in vegetables and dietary agents appear to protect the body against diseases such as cancer. From epidemiologic data, we know that increased consumption of vegetables reduces the risk for certain types of cancer, but now we are beginning to understand the mechanisms by which certain vegetables like broccoli may help our bodies fight cancer and other diseases."
"Angiogenesis is a major issue in cancer metastases," Dr. Singh observed. "Our results provide promising preliminary evidence that constituents of many edible cruciferous vegetables may slow down, or even halt, this process."
Anticancer mechanism of DIM and genistein identified
A presentation at the 2007 Annual Meeting of the American Association for Cancer Research, held this month in Los Angeles, revealed a mechanism by which diindolylmethane (DIM, a compound metabolized from the digestion of cruciferous vegetables), and the soy isoflavone genistein reduce breast and ovarian cancer cells' invasive and metastatic potential. Foods from which the compounds are derived have been associated with a reduction of some cancers, but their mechanisms have not been fully explored.
University of California, Los Angeles graduate student in molecular toxicology Erin Hsu and associates examined the potential of the compounds to interfere with the CXCR4/CXCL12 axis, which is involved in breast cancer metastasis and may also be involved in ovarian cancer. Cancer cells express high levels of the CXCR4 chemokine receptor on their surface. The organs to which the cells metastasize secrete the chemokine ligand CXCL12, which draws the cancer cells, resulting in invasion. By administering DIM or genistein to cancer cells at one end of a compartment, Hsu and her colleagues observed an 80 percent reduction of the cells' migration to CXCL12 at the compartment's other end compared to untreated cells.
The researchers noted that the amount of genistein and DIM used in the experiment is comparable to a high dose of supplements, and would not be achievable by diet alone.
"We think these compounds might slow or prevent the metastasis of breast and ovarian cancer, which would greatly increase the effectiveness of current treatments," Hsu stated. "But we need to test that notion in animals before we can be more definitive."
"We have also tested other phytochemicals and seen similar effects, indicating that this mechanism may mediate protective effects of other vegetable products as well," she added.
Greater magnesium intake linked with lower markers of inflammation and endothelial dysfunction
The April 2007 issue of the American Journal of Clinical Nutrition published the finding of researchers at Harvard University that having a greater intake of magnesium is associated with lower levels of some markers of inflammation and endothelial dysfunction in healthy women. The two conditions often precede atherosclerosis and type 2 diabetes, and are involved in the metabolic syndrome. Magnesium intake has been associated by some studies with a decrease in metabolic syndrome features.
Y. Song of Harvard Medical School and colleagues included 657 participants in the Nurses' Health Study for the current investigation. Blood samples drawn between 1989 and 1990 were analyzed for inflammation markers C-reactive protein, interleukin 6, and soluble tumor necrosis factor alpha receptor 2, and endothelial biomarkers E-selectin, soluble intercellular adhesion molecule 1, and soluble vascular cell adhesion molecule 1. Dietary questionnaires completed by the subjects in 1986 and 1990 were averaged to provide the dietary intake of magnesium and other nutrients.
After adjusted analyses, higher intake levels of magnesium were associated with lower levels of C-reactive protein and E-selectin. The authors write that the direct effect of magnesium on glucose and insulin homeostasis may be responsible for the associations, however they suggest that, alternatively, magnesium may modulate systemic inflammation and endothelial function to influence insulin resistance, explaining that there is increasing evidence implicating the two conditions as its antecedents.
"These observed associations, albeit generally modest, may represent a pathophysiologic mechanism for the pleiotropic effects of magnesium intake on the features of the metabolic syndrome and its associated chronic diseases," the authors conclude.
Greater intake of fish and omega-3 fatty acids linked with reduced cognitive decline
In yet another study to find that fish and omega-3 fatty acids help maintain mental acuity, researchers from the Netherlands found that older men who consumed fish experienced significantly less cognitive decline than men who did not eat fish.
The researchers, from the National Institute for Public Health and the Environment, the Julius Centre for Health Sciences and Primary Care, and Wageningen University, evaluated data from 210 men aged 70 to 89 who were enrolled in the Zutphen Elderly Study, a prospective cohort study of men born between 1900 and 1920 in the Netherlands. Participants were examined in 1985, and cognitive function testing was conducted in 1990 and 1995. Dietary questionnaires completed in 1990 were evaluated for fish intake, fatty acid content, and other factors. Men included in the current investigation were free of heart attack, stroke, diabetes and cancer at the beginning of the study.
Twenty-four percent of the men did not eat fish, 41 percent consumed up to 20 grams per day, and 35 percent consumed more than 20 grams. Although there was no difference in their cognitive function in 1990, men who did did not consume fish experienced a subsequent five-year cognitive decline four times greater than that of men who were fish eaters. When omega-3 fatty acids EPA and DHA were examined, there was a dose-response relationship observed between intake and cognitive decline. Men whose intake placed them among the top one-third of participants experienced significantly less cognitive decline than those whose intake was in the lowest third.
"The current study provides evidence that a combined daily intake of approximately 400 milligrams omega-3 polyunsaturated fatty acids EPA and DHA is associated with less subsequent cognitive decline in elderly men," the authors conclude.
Mediterranean diet protects against childhood allergy and asthma
A report published ahead of print in the journal Thorax described the finding that Crete's traditional "Mediterranean" diet may provide protection from the development of allergic rhinitis and asthma in children. The incidence of these conditions is rare on this Greek Island, although skin allergy is not uncommon.
Paul Cullinan of Royal Brompton Hospital and the National Heart and Lung Institute in England, along with collaborators in Crete evaluated data from 690 children aged 7 to 18 residing on the island. Questionnaires completed by the subjects' parents provided information on the children's diets and allergy and respiratory symptoms. Adherence to a Mediterranean diet was determined by the intake of 12 different foods, including fruits, vegetables, whole grains, legumes, nuts, and olive oil.
Eighty percent of the children were reported to consume fresh fruit, and 68 percent consumed fresh vegetables at least twice per day. Greater adherence to the Mediterranean diet was associated with a reduction in the symptoms of asthma and skin allergy, and were stronger against allergic rhinitis. Adjusted analysis of the data found that grapes, which contain high amounts of antioxidants and resveratrol, were especially associated with protection against allergic rhinitis and wheezing. Oranges, apples and tomatoes also appeared to be protective, but were not associated with skin allergy. High nut consumption, defined as including nuts in the diet at least three times per week, halved the risk of wheezing, which could be attributable to their vitamin E and magnesium content. A high intake of margarine doubled the risk of allergic rhinitis and asthma.
"Our data suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis," the authors conclude. "Diet may explain the relative lack of allergic symptoms in this population."
More cancer-preventive evidence for vitamin D
The March, 2007 issue of the journal Cancer Epidemiology Biomarkers & Prevention published the finding of researchers at Mt Sinai Hospital in Toronto that early exposure to vitamin D, whether via sun exposure or diet, may help protect women from developing breast cancer.
Julia A Knight, of Mt Sinai's Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute and her associates compared information from 972 women with invasive breast cancer with 1,135 healthy control subjects. Questionnaires answered by the participants provided information on demographics, established breast cancer risk factors, lifetime sun exposure, and diet.
Not surprisingly, women with breast cancer were likelier to have such known risk factors as early menarche or a first-degree relative who had been diagnosed with the disease. When sun exposure was evaluated, having fewer outdoor activities, being less likely to work outdoors, covering the limbs, having experienced less tanning or burning, and consuming less cod liver oil were each found to be associated with increased breast cancer risk. When diet was examined, more frequent consumption of milk (commonly fortified with vitamin D), was associated with a reduction in breast cancer risk, and more servings of salmon and tuna per week appeared to be marginally protective. The use of vitamin supplements was also associated with a lower risk of the disease.
When the participants' exposure to vitamin D was evaluated according age, there was little evidence for a protective benefit of exposure for women between the ages of 45 and 54, and more evidence for women between the ages of 10 and 19. "We found strong evidence to support the hypothesis that vitamin D could help prevent breast cancer," the authors conclude. "However, our results suggest that exposure earlier in life, particularly during breast development, may be most relevant."
Fish oil gives statins a boost
The March 31, 2007 issue of The Lancet published the finding of the Japan EPA Lipid Intervention Study (JELIS) that the omega-3 fatty acid eicosapentaenoic acid (EPA) found in fish oil could be used in addition to statin drugs to provide additional protection against coronary artery disease. The study is the first major long-term interventional trial to evaluate this effect.
Mitsuhiro Yokoyama of Kobe University Graduate School of Medicine and colleagues randomized 18,645 men and women with a total cholesterol of at least 6.5 micromoles per liter to receive 1800 milligrams EPA with a statin drug, or a statin drug only for a five year period during which major coronary events were noted. Serum cholesterol levels were measured at the beginning and conclusion of the trial.
At the end of an average 4.6 years of follow up, LDL cholesterol concentrations had decreased by an average of 25% in both groups. A 19 percent reduction in major coronary events occurred in the group that received EPA compared to those that received a statin only. Unstable angina and nonfatal events were similarly reduced.
“This study shows that EPA, at a dose of 1800 mg per day, is a very promising regimen for prevention of major coronary events, especially since EPA seems to act through several biological mechanisms," the authors conclude. "We need to investigate whether EPA is effective for prevention of major coronary events in hypercholesterolemic patients without or with coronary artery disease in other countries”.
“Compared with drugs, invasive procedures, and devices, modest dietary changes are low risk, inexpensive, and widely available," Dariush Mozaffarian of Harvard wrote in an accompanying commentary."The JELIS investigators should be commended, and their efforts should inspire additional clinical trials of the effects of fish oil and other dietary factors and habits on cardiovascular health”.