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Grape seed extract proves toxic to head and neck cancer cells
January 30, 2012. Researchers at the University of Colorado report online on January 19, 2012 in the journal Carcinogenesis that grape seed extract shows an ability to reduce the growth of head and neck squamous cell carcinoma when administered to cell cultures and mice.
"It's a rather dramatic effect," commented lead researcher Rajesh Agarwal, PhD, who is a professor at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences. "Cancer cells are fast-growing cells. Not only that, but they are necessarily fast growing. When conditions exist in which they can't grow, they die."
Dr Agarwal and his associates tested the effects of grape seed extract in cultures of human head and neck squamous cell carcinoma as well as normal human epidermal cells. The researchers observed a reduction in growth, along with cell cycle arrest and programmed cell death in the cancerous cells. Grape seed was found to damage the DNA of the cancer cells while inhibiting its repair. The authors attribute grape seed's growth inhibitory, DNA-damaging and apoptotic effects to the accumulation of intracellular reactive oxygen species, a phenomenon that was reversed by the administration of the antioxidant N-acetylcysteine. Similarly, in an experiment involving mice that received transplanted head and neck squamous cell carcinoma tumors, animals that received grape seed extract had a reduction in cancer cell growth compared with those who did not receive the extract. In both experiments, healthy tissue remained unharmed.
"We saw absolutely no toxicity to the mice, themselves," Dr Agarwal emphasized. "I think the whole point is that cancer cells have a lot of defective pathways and they are very vulnerable if you target those pathways. The same is not true of healthy cells."
The researchers hope to test grape seed in human patients who have failed first line therapies.
Higher vitamin D levels predict improved survival among colorectal cancer patients
January 27, 2012. An article published online on January 25, 2012 in Cancer Epidemiology, Biomarkers and Prevention reports an association between higher prediagnostic levels of vitamin D and increased survival among patients with colorectal cancer.
The study evaluated the association between serum vitamin D levels and mortality among 1,202 men and women enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which recruited over 520,000 participants from 1992 to 1998. Subjects in the current study were diagnosed with colorectal cancer between enrollment and June 2003. Blood samples obtained upon recruitment were analyzed for serum 25-hydroxyvitamin D [25(OH)D]. Over a mean follow-up period of 73 months, 444 deaths due to colorectal cancer and 97 deaths from other causes occurred.
Men and women whose serum vitamin D levels were among the top 20 percent of participants had a 31 percent lower risk of dying from colorectal cancer and a 33 percent lower risk of mortality from any cause compared to those whose levels were among the lowest 20 percent. Having a high vitamin D level was protective against cancers of both the colon and the rectum. When subjects were analyzed according to calcium intake, a significant protective effect of vitamin D was observed only among those with high dietary calcium.
"If verified in other studies, calcium supplementation in combination with vitamin D may be potentially useful for improved survival in colorectal cancer patients," the authors write. "This large and comprehensive study, based on the EPIC cohort has shown that higher blood vitamin D levels before colorectal cancer diagnosis are associated with reduction in colorectal cancer-specific and overall mortality. Further prognostic studies among cancer patients are needed to determine whether 25(OH)D levels at diagnosis and post-diagnosis correlate with those measured prior to diagnosis, and influence all-cause and disease-specific survival among colorectal cancer patients."
The worm paradox
January 25, 2012. While the relatively lengthy and healthy life of the French people has long been attributed to be the result of their moderate consumption of wine, researchers have recently observed that a small amount of alcohol also benefits a well-studied worm known as Caenorhabditis elegans. In fact, a diluted amount of ethanol more than doubles the worms' life span, according to a report published on January 18, 2012 in the journal PLoS ONE. The finding could shed light on human studies that have revealed positive effects on cardiovascular and all-cause mortality in association with moderate alcohol intake.
University of California Los Angeles professor of chemistry and biochemistry Steven Clarke, PhD and his associates stumbled upon the finding when testing the effects in C. elegans larvae of the administration of cholesterol dissolved in ethanol. "It's just a solvent, but it turns out the solvent was having the longevity effect," Dr Clarke stated. "The cholesterol did nothing. We found that not only does ethanol work at a 1-to-1,000 dilution, it works at a 1-to-20,000 dilution. That tiny bit shouldn't have made any difference, but it turns out it can be so beneficial."
"The concentrations correspond to a tablespoon of ethanol in a bathtub full of water or the alcohol in one beer diluted into a hundred gallons of water," he said. "This finding floored us — it's shocking."
While the worms normally survive for fifteen days, Dr Clarke reported that "Our finding is that tiny amounts of ethanol can make them survive 20 to 40 days."
"While the physiological effects of high alcohol consumption have been established to be detrimental in humans, current research shows that low to moderate alcohol consumption, equivalent to one or two glasses of wine or beer a day, results in a reduction in cardiovascular disease and increased longevity," added coauthor Shilpi Khare. "While these benefits are fascinating, our understanding of the underlying biochemistry involved in these processes remains in its infancy."
Luteolin shows promise as an agent to reduce colon cancer cell growth
January 23, 2012. In an article published today in the journal BMC Gastroenterology, Korean researchers report a benefit for the flavonoid luteolin, which occurs in some fruits and vegetables, in reducing the growth of cultured colon cancer cells.
In earlier research, Professor Jung Han Yoon Park of Hallym University in Chuncheon and colleagues found that luteolin decreases the growth of colon cancer cells by stimulating programmed cell death (apoptosis) and cell cycle arrest. In the current study, the team cultured the cells with luteolin and/or insulin-like growth factor-1 (IGF-1), which stimulates cancer growth.
A reduction in the secretion of insulin-like growth factor II (IGF-II) occurred in colon cancer cells treated with luteolin, and a decline in levels of IGF receptor precursor protein was observed within two hours. IGF-II occurs in higher levels in colon cancer cells compared to normal colon cells, and is believed to induce uncontrolled cell division and growth in cancer. When administered with IGF-1, luteolin also inhibited IGF-1's growth stimulatory effect, by affecting the cell signaling pathways that IGF-1 activates in cancer.
"Luteolin reduced IGF-I-dependent activation of the cell signaling pathways PI3K, Akt, and ERK1/2 and CDC25c," stated Jung Han Yoon Park, who is also affiliated with Kangwon National University. "Blocking these pathways stops cancer cells from dividing and leads to cell death. Our study, showing that luteolin interferes with cell signaling in colon cancer cells, is a step forward in understanding how this flavonoid works. A fuller understanding of the in vivo results is essential to determine how it might be developed into an effective chemopreventive agent."
Polyphenol as well as alcohol content contribute to wine benefit
January 20, 2012. A report published in the February, 2012 issue of the American Journal of Clinical Nutrition reveals that the alcohol content of wine and the polyphenols it contains both contribute to the beverage's cardioprotective effects, but in different ways. The research helps answer the question concerning whether wine's benefits are due to its alcohol content or other factors.
A team from Spain enrolled 67 men who were at high risk of cardiovascular disease due to smoking or other risk factors. Following a two week period during which no alcohol was consumed, the participants were divided to receive red wine, dealcoholized red wine or gin daily for four weeks. This was followed by two similar trials of the beverages not previously received by each subject. Blood and urine samples were collected at the beginning and end of each treatment period, and analyzed for markers of inflammation and other factors.
The researchers found an increase in interleukin-10 (an anti-inflammatory cytokine) and a reduction in macrophage-derived chemokines in association with alcohol, while red wine polyphenols were associated with reduced intercellular adhesion molecule-1 and interleukin-6, as well as other factors. "The phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease," the authors conclude.
In a review of the study, one author commented that "The results strongly indicate an effect of wine polyphenols on inflammation and this is just what we expect from the biochemistry and nutritional effects of fruits and vegetables. The effect of ethanol, on the other hand, likely fits a hormetic mechanism, where low doses regularly supplied are protective while high doses in a single shot are worsening the progression of disease."
Fewer calories equal longer telomeres in men
January 18, 2012. An article published online on January 11, 2012 in the American Journal of Clinical Nutrition reveals the presence of longer telomeres among men who consume fewer calories in comparison with those who consumed more. Telomeres are protective caps at the ends of chromosomes that shorten with age, and are used as a biomarker of cellular aging.
Researchers from Hebrew University in Israel and the University of Medicine and Dentistry of New Jersey analyzed data from 405 men and 204 women who participated in the Jerusalem LRC Prevalence Study, a long term observational study of Jerusalem residents. Leukocyte (white blood cell) telomere length was measured in blood samples obtained between 1989 and 1991 and at follow-up (which averaged 13.1 years after baseline). Dietary questionnaire responses provided data on daily calories and foods consumed.
Lower calorie intake at baseline and follow-up were associated with longer telomere length in men, whereas the association with women was not significant. Further analysis determined that the association was restricted to those who never smoked. Of foods consumed, decreased unsaturated fatty intake had the strongest association with longer telomeres. "We found calorie intake at a mean age of 30 years to be significantly inversely associated with leukocyte telomere length at the mean ages of 30 and 43 years but not with leukocyte telomere length change during the relatively brief 13 year window of follow-up," the authors write. "This finding was confined to men and was evident for all of the macronutrients (although more so for unsaturated fatty acids), suggesting that energy per se, and not specific nutrients, might play a role."
"The inverse calorie intake–leukocyte telomere length association is consistent with trial data showing beneficial effects of calorie restriction on aging biomarkers," they conclude.
Arthritis linked to ultra short telomeres
January 16, 2012. Writing in an article that appeared online on January 16, 2012 in the journal Arthritis Research & Therapy, Danish researchers report their discovery of a higher incidence of knee osteoarthritis (OA) among individuals who have ultra short telomeres. Telomeres, which are protective caps that reside at the ends of the chromosomes, shorten with age and telomere length has been associated with cellular aging and longevity. Abnormally short telomeres can be the result of sudden cell damage, and have been observed in some types of cancer. In their introduction to the article, Maria Harbo of the University of Southern Denmark and her colleagues remark that aged cartilage cells exhibit behavior typical of senescent cells in which telomere shortening is believed to play a prominent role.
Dr Harbo's team examined telomere length in cells derived from the knees of women who had joint replacement surgery. "We see both a reduced mean telomere length and an increase in the number of cells with ultra short telomeres associated with increased severity of osteoarthritis, proximity to the most damaged section of the joint, and with senescence," Dr Harbo reported. "Senescence can be most simply explained as biological aging and senescent cartilage within joints is unable to repair itself properly."
"The telomere story shows us that there are, in theory, two processes going on in osteoarthritis," she added. "Age-related shortening of telomeres, which leads to the inability of cells to continue dividing and so to cell senescence, and ultra short telomeres, probably caused by compression stress during use, which lead to senescence and failure of the joint to repair itself. We believe the second situation to be the most important in OA. The damaged cartilage could add to the mechanical stress within the joint and so cause a feedback cycle driving the progression of the disease."
Grapes may protect against macular degeneration
January 13, 2012. An article published online on December 8, 2011 in the journal Free Radical Biology and Medicine shows a protective effect for grapes and lutein against the development of age-related macular degeneration (AMD) in a mouse model of the disease.
In their introduction to the article, Silvia Finnemann, PhD of Fordham University's Department of Biological Sciences and her associates explain that oxidative damage and pro-oxidant lysosomal lipofuscin accumulate in the aging human eye, which causes a decline in function of the retinal pigment epithelium: the support cells for the retina's photoreceptors. The resulting dysfunction and destruction of these cells, in turn, contributes to the development of age-related macular degeneration.
For their study, Dr Finnemann's team administered diets that provided natural antioxidants, grapes or marigold extract containing the macular pigments lutein/zeaxanthin to mice bred to have increased blood vessel formation (which occurs in macular degeneration). While lutein and zeaxanthin proved to be protective to the eye, grapes showed the greatest benefit, with both compounds resulting in reduced lipofuscin accumulation and age related rod and cone photoreceptor dysfunction, prevention of blindness, and other positive outcomes. The antioxidant properties of compounds that occur in grapes are believed to be the protective mechanism observed in the current research.
"The protective effect of the grapes in this study was remarkable, offering a benefit for vision at old age even if grapes were consumed only at young age," Dr Finnemann stated. "A lifelong diet enriched in natural antioxidants, such as those in grapes, appears to be directly beneficial for retinal pigment epithelium, and retinal health and function."
Majority of postmenopausal women need more vitamin D
January 11, 2012. A Position Statement prepared by the European Menopause and Andropause society (EMAS) published in the January, 2012 issue of the journal Maturitas reveals an undesirably low level of vitamin D in postmenopausal women and suggests the use of vitamin D2 or vitamin D3 supplements accompanied by monitoring when needed. The text was signed by 11 international experts and defines optimal blood levels as ranging between 30 to 90 nanograms per milliliter. "We believe that many diseases can be aggravated by a chronic deficiency of vitamin D," stated project leader Faustino R. Pérez-López of the University of Zaragoza. "We analyzed the conditions and diseases that are associated with vitamin D deficiency and we recommended the intake of supplements in postmenopausal women."
Reduced vitamin D levels are estimated to affect 50 to 70 percent of Europeans. "Healthcare professionals should be aware that this is a common problem which affects a large part of the population in Europe, even those who live in sunny places," Dr Pérez-López noted. "The World Health Organisation or other relevant bodies belonging to the European Union should establish minimum requirements or recommendations on the fortification of foods with vitamin D."
Although the medical community still has not reached a consensus concerning vitamin D supplements, Dr Pérez-López remarked that "they are effective but its efficacy has not yet been accepted." He recommended that "Patients with risk factors associated with hypovitaminosis (obesity, pigmented skin, intestinal malabsorption syndromes and living in regions close to the North and South poles) should increase their intake to up to 4,000 IU per day."
"It is unknown what will happen in the future but we make our recommendations from the EMAS," he concluded. "This is the first statement on the matter in Europe directed towards menopausal women."
Red wine may be more protective than white wine against breast cancer
January 09, 2012. While increased alcohol intake in general has been associated with elevated breast cancer risk, the results of a study published online on December 7, 2011 in the Journal of Women's Health indicate that elements in red wine could be protective against the development of the disease. "Aromatase inhibitors prevent the conversion of androgens to estrogen and occur naturally in grapes, grape juice, and red, but not white wine," the authors note in their introduction to the article.
In a cross-over study, Glenn D. Braunstein, MD and his associates at Cedars-Sinai Medical Center in Los Angeles assigned 36 premenopausal women to eight ounces of red wine daily for one month followed by eight ounces of white wine for one month, or the reverse regimen. Blood samples collected at two points during the women's menstrual cycles were analyzed for the hormones estradiol, estrone, androstenedione, total and free testosterone, sex hormone binding globulin, luteinizing hormone and follicle stimulating hormone.
In addition to elevations of luteinizing hormone and free testosterone, the team found a small reduction in estrogen levels among participants who consume red wine for one month in comparison with those who consumed white wine. In contrast, alcohol in general has been shown to increase the body's estrogens, which fuels the most common type of breast cancer. "There are chemicals in red grape skin and red grape seeds that are not found in white grapes that may decrease breast cancer risk," stated Dr Braunstein, who is vice president for Clinical Innovation and the James R. Klinenberg, MD, Chair in Medicine at Cedars-Sinai.
"If you were to have a glass of wine with dinner, you may want to consider a glass of red," remarked study coauthor Chrisandra Shufelt, MD, who is an assistant director of the Women's Heart Center at the Cedars-Sinai Heart Institute. "Switching may shift your risk."
Increased flavonoid consumption associated with reduced cardiovascular deaths
January 06, 2012. An article published online on January 4, 2012 in the American Journal of Clinical Nutrition reveals a lower risk of dying of cardiovascular disease among those who consumer more flavonoids: plant-based phytochemicals that may be responsible in part for the reduced risk of heart disease observed among those who consume a diet that contains high amounts of vegetables, fruit and other plant foods.
American Cancer Society and Tufts University researchers evaluated data from 38,180 men and 60,289 women who had no history of heart disease upon enrollment in the Cancer Prevention Study II Nutrition in 1999. Dietary questionnaire responses were analyzed for the intake of seven classes of flavonoids, including flavan-3-ols, flavanones, flavones, flavonols, isoflavones, anthocyanidins and proanthocyanidins from a variety of plant foods. The subjects were followed for seven years, during which 1,589 men and 1,182 women died from cardiovascular disease.
Subjects whose total flavonoid intake was among the top one-fifth of participants had an 18 percent lower risk of dying from cardiovascular disease compared to those whose intake was among the lowest fifth. Among classes of flavonoids, increased intake of flavon-3-ols, flavones, flavonols, anthocyanidins and proanthocyanidins were associated with a reduction in the risk of fatal cardiovascular disease. For men, the protective effect of increased total flavonoids was greater for stroke than for heart disease.
Flavonoids' possible cardioprotective mechanisms involve antioxidant, anti-inflammatory and vascular effects. "Our findings indicate that total flavonoids and several classes, especially flavones, are associated with lower risks of fatal cardiovascular disease," the authors write. "The finding that benefits of flavonoid consumption were realized at relatively low intake thresholds deserves further examination. If these findings are replicated, recommendations for food sources rich in specific flavonoids should be considered for cardiovascular disease risk reduction."
Is manganese the missing mineral in osteoporosis?
January 04, 2012. A hypothesis submitted by researchers at the University of Castilla-La Mancha in Spain, published in the January, 2012 Frontiers of Bioscience Elite Edition, suggests that a lack of manganese rather than calcium could be the cause of osteoporosis, a disease characterized by progressive thinning of the bones that is common among older individuals, particularly women.
By studying deer antlers, Tomás Landete of the University's Research Institute of Hunting Resources (IREC) and his associates discovered an association between manganese depleted diets in 2005 and increased breakage. "Previous antler studies show that manganese is necessary for calcium absorption," commented Dr Landete. "Our hypothesis is that when the human body absorbs less manganese or when it is sent from the skeleton to other organs that require it, such as the brain, the calcium that is extracted at the same time is then not properly absorbed and is excreted in the urine. It is in this way that osteoporosis can slowly strike."
"Antlers grow by transferring 20% of the skeleton's calcium towards their structure," he added. "We therefore saw that it was not calcium deficiency that caused the weakening but rather the deficiency of manganese. The lack of manganese was almost as if the 'glue' that sticks calcium to antlers bones was missing."
The researchers suggest that osteoporosis caused by a lack of manganese could precede brain disorders including Alzheimer's and Parkinson's disease. A comparison of 45 osteoporosis patients and 68 subjects with osteoarthritis who underwent surgery between 2008 and 2009 found that 40 percent of those who had osteoporosis exhibited some type of cerebral dysfunction while none of those who had osteoarthritis showed signs of the condition.
"We are collecting human bones to confirm this," Dr Landete stated. "However, studies on rats in which Alzheimer's disease has been induced by aluminum intoxication show that as the severity of this disease increases, manganese levels in the bones decrease."
Adherence to Mediterranean Diet, Recommended Food Score predict longer life
January 02, 2012. A report published online on December 21, 2011 in the Journal of Nutrition reveals a protective effect for two healthy diets on mortality from any cause over a 14 year average follow-up period.
A team from Australia and the UK analyzed the diets of 972 participants in the British Diet and Nutrition Survey of men and women aged 65 and older upon enrollment from 1994-1995. Four day weighed food intake records were analyzed according to their adherence to the Healthy Diet Score, which rates the intake of saturated fatty acids, polyunsaturated fatty acids, protein, carbohydrates, fiber, fruit and vegetables, pulses and nuts, sugars, cholesterol, fish, red meat and meat products, and calcium; the Mediterranean diet, which includes vegetables, legumes, fruits and nuts, cereals, fish and seafood, a high monounsaturated to saturated fats ratio, dairy products, meat and meat products, and alcohol; and the Recommended Food Score which, according to the authors, "is a food-based score calculated based on the frequency of consumption of a range of foods considered to be consistent with existing dietary guidelines," including various fruits, vegetables, whole grains, lean meat and reduced fat dairy products.
Having a higher Mediterranean Diet Score was associated with a 23 percent lower adjusted risk of dying over follow-up than having a low score, and a higher Recommended Food Score was associated with a 33 percent lower risk. No association was found for the Healthy Diet Score.
"The study shows that diet quality is an important predictor of longevity among older adults," Sarah A. McNaughton and her colleagues write. "With the ageing population worldwide, the role of diet quality in improving functional status and quality of life becomes increasingly important and further research is required on the role of diet in these aspects of ageing."
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