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Amino acid supplements restore glutathione synthesis in aged men and women
Researchers at Baylor College of Medicine in Houston report online in the American Journal of Clinical Nutrition the finding of a reduction in glutathione synthesis in older individuals, which can be reversed by supplementing with the precursor amino acids N-acetylcysteine (NAC) and glycine.
Glutathione is a tripeptide antioxidant compound associated with protection against reactive oxygen species. According to the authors, glutathione is the most abundant endogenous intracellular antioxidant, whose decline with aging results in increased oxidative stress, a phenomenon associated with age-related disease. "We hypothesized that blunted glutathione synthesis could be responsible for intracellular glutathione deficiency and consequent oxidative stress in aging," they write. "We further hypothesized that dietary supplementation with two amino acid precursors of glutathione—cysteine and glycine—would boost glutathione synthesis and lower oxidative stress."
The team measured red blood cell glycine, cysteine and glutathione levels, glutathione synthesis, oxidative stress and oxidant damage in eight men and women between the ages of 30 and 40, and eight men and women aged 60 to 75. The older group subsequently received two weeks of oral supplementation with N-acetylcysteine and glycine, and their blood was retested.
Older participants had significantly lower levels of glycine, cysteine and glutathione, lower glutathione synthesis rates, and greater oxidative stress and damage compared to younger subjects at the beginning of the study. At the end of the supplementation period, no differences in these measures were observed between the supplemented older participants and unsupplemented younger subjects."Glutathione deficiency in elderly humans occurs because of a marked reduction in synthesis," Rajagopal V. Sekhar and colleagues conclude. "Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and concentrations and lowers levels of oxidative stress and oxidant damages. These findings suggest a practical and effective approach to decreasing oxidative stress in aging."
Higher vitamin C levels linked with lower blood pressure
Researchers in England evaluated data from 20,926 men and women aged 40 to 79 years who enrolled in the European Prospective Investigation Into Cancer-Norfolk prospective population study between 1993 and 1997. Blood pressure, plasma vitamin C and other factors were measured at the participants’ initial clinic visit. Questionnaire responses provided information on medical conditions, antihypertensive medication use and vitamin C intake from supplements.
For those whose plasma vitamin C levels were among the top 25 percent of participants, the adjusted risk of having hypertension, defined as systolic blood pressure of at least 140 mm Hg, was 22 percent lower than those whose levels were among the lowest fourth. Exclusion of subjects who used vitamin C supplements or antihypertensive drugs failed to modify the finding. Each 20 micromole per liter increase in plasma vitamin C, which is associated with consuming one additional serving of fruit and vegetables daily, was related to a 0.9 mm Hg reduction in systolic blood pressure.
Phyo K. Myint and colleagues remark that vitamin C is a well known antioxidant, and that oxidative stress plays a major role in hypertension. The vitamin also acts as a vasodilator by increasing the bioavailability of nitric oxide.“The magnitude of the association between fruit and vegetable consumption depicted by plasma vitamin C concentration and blood pressure is considerable and independent of known major risk factors for high blood pressure,” the authors write. “Future studies should be focused not only on quantity but on quality and type of fruit and vegetable consumption to better understand the association between dietary lifestyle behavior and blood pressure.”
Meta-analysis associates increased fiber intake associated with breast cancer risk reduction
The results of a meta-analysis published online on July 20, 2011 in the American Journal of Clinical Nutrition reveals a significant protective effect for increased fiber consumption on the risk of breast cancer.
For their review, Li-Quiang Qin of Soochow University in Suzhou, China and colleagues selected 10 prospective studies of the effect of fiber on breast cancer risk, which included a total of 712,195 women. Fiber intake was estimated from the participants’ dietary questionnaire responses. Follow-up periods ranged from 4.3 to 18 years, during which 16,848 cases of breast cancer were diagnosed.
Eight of the ten studies analyzed found a lower risk of breast cancer associated with greater fiber intake. Subjects whose intake of fiber was among the highest 20 percent of participants averaged an 11 percent lower risk of the disease compared to those whose intake was among the lowest 20 percent. For every 10 gram per day intake of fiber, the risk of breast cancer decreased by 7 percent. Length of follow-up or menopausal status did not appear to impact the association between breast cancer and fiber determined by the analysis.
Possible protective mechanisms for fiber include reduction of circulating estrogen concentrations via increased excretion of the hormone in feces, in addition to involvement in the control and insulin resistance and insulin-like growth factors, which have been associated with breast cancer.“Although the magnitude of risk reduction reported here is small at the individual level, given the high incidence and large burden of breast cancer, increasing dietary fiber intake in the general population is of great public health significance with respect to breast cancer prevention,” the authors note. “In conclusion, this meta-analysis of prospective cohort studies provides evidence of a significant inverse dose-response association between dietary fiber intake and risk of breast cancer.”
Long term antioxidant supplementation linked with better memory
Results from the French SU.VI.MAX trial indicate that supplementing with antioxidants could help middle aged people maintain memory skills that often decline with aging.
“Oxidative stress and a proinflammatory state were hypothesized to play a central role in dementia and the decline of age-related cerebral functions through lipid peroxidation,” write Emmanuelle Kesse-Guyot of the Université Paris and her associates in an article published online on July 20, 2011 in the American Journal of Clinical Nutrition. Because of the brain’s particular vulnerability to reactive oxygen species, ensuring an adequate intake of antioxidants is likely to be neuroprotective.
The team analyzed data from 4,447 participants aged 45 to 60 in the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) randomized trial. From 1994 to 2002, subjects received a daily placebo or combination of 6 milligrams beta carotene, 120 milligrams vitamin C, 30 milligrams vitamin E, 100 micrograms selenium and 20 milligrams zinc. Four tests of cognitive performance were administered beginning at five years following the end of the treatment period.
Participants who received the antioxidants had significantly better episodic memory and semantic fluency scores, while verbal memory scores improved among only the antioxidant recipients who had low serum vitamin C levels at the beginning of the study or who were nonsmokers. “These results suggested that a beneficial effect of low doses of antioxidants, which are easily reached through the diet, on cognitive functions may persist a long time after the end of the supplementation, particularly within specific subgroups with an inadequate antioxidant status at baseline,” the authors write.“Additional investigations of the association between antioxidants and cognitive function that are based on randomized controlled trial testing of low-dose antioxidant supplementation are required to confirm our findings,” they conclude.
Meta-analysis associates green tea consumption with lower cholesterol
The results of a meta-analysis published online on June 29, 2011 in the American Journal of Clinical Nutrition adds more evidence to a purported cardiovascular benefit for drinking green tea.
Researchers at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing reviewed 14 randomized controlled trials that evaluated the effects of a green tea beverage or extract on serum lipids. The trials included a total of 1,136 men and women. While consuming green tea appeared to have no effect on high-density-lipoprotein (HDL) cholesterol, it was significantly associated with reductions in serum low-density lipoprotein (LDL) cholesterol as well as triglycerides, in subjects with and without cardiovascular risks. Men and women who received green tea experienced an average reduction in LDL of 2.19 milligrams per deciliter, and a 7.2 milligram per deciliter reduction in triglycerides. The results were not affected by the type of study, catechin dose, trial duration or health status of the participants.
The authors suggest that inhibition of cholesterol absorption is a primary mechanism for tea catechins in reducing serum cholesterol in addition to a possible direct inhibitory effect on cholesterol synthesis. They note that tea’s effects are similar to those of statin drugs, which decrease cholesterol synthesis and increase the LDL receptor, which helps remove LDL from circulation.
“These results suggested that green tea may be incorporated into a targeted dietary program as part of public health policy to improve cardiovascular health,” they write. “Because most Americans drink high calorie beverages or alcohol on a daily basis, and only 20% of Americans consume low-calorie green tea, the potential for meaningful intervention is real.”
Nerves need vitamin C
An article published online on June 29, 2011 in the Journal of Neuroscience reveals that the eye’s nerve cells need vitamin C, which suggests the vitamin may be required by other areas of the nervous system.
Henrique von Gersdorff, PhD of Oregon Health & Science University (OHSU) and his associates studied goldfish retinal cells, which are similar to those found in humans. They found that the cells’ GABA-type receptors, which assist in the modulation of communication between nerve cells, cease to function properly in the absence of vitamin C. Because these cells are a type of brain cell, the researchers believe that GABA receptors in other parts of the brain may also need vitamin C, and that the vitamin’s antioxidant property helps preserve the cells and receptors from breakdown due to oxidative stress.
"We found that cells in the retina need to be 'bathed' in relatively high doses of vitamin C, inside and out, to function properly," commented Dr von Gersdorff, who is a senior scientist at OHSU's Vollum Institute "Because the retina is part of the central nervous system, this suggests there's likely an important role for vitamin C throughout our brains, to a degree we had not realized before . . . Perhaps the brain is the last place you want to lose vitamin C."The findings may have implications for other diseases caused by dysfunction of nerve cells in the retina and brain due to GABA receptor malfunction. "For example, maybe a vitamin C-rich diet could be neuroprotective for the retina — for people who are especially prone to glaucoma," Dr von Gersdorff stated. "This is speculative and there is much to learn. But this research provides some important insights and will lead to the generation of new hypotheses and potential treatment strategies."
Shortened telomeres associated with elevated emphysema risk
A report published online on July 15, 2011 in American Journal of Respiratory and Critical Care Medicine reveals the discovery of Johns Hopkins researchers of a connection between shorter telomeres—the DNA structures that protect the ends of the body’s chromosomes--and the risk of emphysema. Telomeres shorten with age, and are recognized as a marker of cellular aging.
Johns Hopkins School of Medicine assistant professor of oncology Mary Armanios, MD and her associates compared the effects of six months of cigarette smoke exposure in normal mice and mice bred to have short telomeres. “With age, short telomeres accumulate and cause cells to stop dividing,” Dr Armanios explained. “Telomeres can be thought of as 'biological clocks'. We wanted to determine whether telomere length itself was why susceptibility to emphysema increases with age."
"We found that in mice that have short telomeres, there was a significant increased risk of developing emphysema after exposure to cigarette smoke," Dr Armanios reported. "Although the mice had no lung disease at baseline, after exposure to cigarette smoke, they surprisingly developed emphysema. In contrast, mice with long telomeres did not develop lung disease during our experiments."
"We found that cells with damaged DNA stopped dividing, and lung cells with too much damage could no longer be repaired, thus contributing to the emphysema,” she observed. “These results are one of the clearest examples of telomere length, which is an inherited factor, interacting with an environmental insult to cause disease. In fact, our results in mice suggest that short telomeres might contribute to how cigarette smoke accelerates aging in the lung in some individuals."
"Now that we have examined the question of susceptibility in a rigorous genetic model, we can begin to study how telomere length affects emphysema risk in susceptible populations."
More potassium, less sodium linked with fewer deaths over more than a decade
In the July 11, 2011 issue of the AMA journal Archives of Internal Medicine, a team from the Centers for Disease Control in Atlanta and the Harvard School of Public Health report that having a lower sodium to potassium ratio is associated with a reduced risk of dying from any cause over a 14.8 year median period.
Quanhe Yang PhD and colleagues evaluated data from 12,267 adults enrolled in the Third National Health and Nutrition examination Survey Linked Mortality File, a cohort study of all-cause and cardiovascular and ischemic heart diseases mortality. Over a 14.8 year median follow-up period, 2,270 deaths occurred, which included 825 deaths from cardiovascular disease and 433 from ischemic heart disease.
While having a higher sodium intake was associated with a 20 percent higher adjusted risk of dying over follow up, high potassium intake was associated with a 20 percent lower risk. Those whose sodium to potassium ratio was among the top 25 percent of subjects had a 46 percent greater risk of dying from any cause or from cardiovascular disease, and more than twice the risk of dying of ischemic heart disease compared with those whose ratio was lowest.
“Critical issues are whether dietary or pharmacological potassium supplementation would have the same health benefits as consumption from traditional dietary sources and whether the form of potassium matters,” write Lynn D. Silver, MD, MPH and Thomas A. Farley, MD, MPH in an accompanying commentary. “While potassium supplementation may prove to be of benefit to many persons, a considerable number are at high risk for hyperkalemia. Yet some studies suggest that the greater harm may arise from inadequate intake.“
Dr Yang and colleagues conclude that “Public health recommendations should emphasize simultaneous reduction in sodium intake and increase in potassium intake.”
Vitamin D helps rid the brain of Alzheimer’s plaque
A report published online on July 8, 2011 in the journal Fluids and Barriers of the CNS describes experiments conducted by a team from Tohoku University in Japan which found a role for vitamin D in clearing the brain of amyloid beta, a toxic compound that accumulates in the plaques that occur in the brains of Alzheimer’s disease patients. “It was reported that single nucleotide polymorphisms in the vitamin D receptor (VDR) gene increase the risk of impairment of cognitive function and developing Alzheimer’s disease, suggesting a relation between serum vitamin D levels and risk of Alzheimer’s disease,” the authors write in their introduction to the article.
Professor Tesuya Terasaki and his colleagues at Tohuko University’s Graduate School of Pharmaceutical Sciences injected mice with 1 alpha,25-dihydroxyvitamin D3 (the active form of vitamin D3 in the body), the herbal compound forskolin, or a control substance. The animals were then examined to determine the rate of amyloid beta clearance and brain levels after 24 hours.
The rate of elimination of amyloid beta across the blood brain barrier was 1.3 times greater in mice that received vitamin D compared to those that received the control substance. At 24 hours, endogenous amyloid beta levels were significantly lower in the vitamin D-treated group.Forskolin was also shown to enhanced amyloid beta removal from the animals’ brains and while its action appears to be nongenomic, vitamin D’s actions were determined to be both genomic and nongenomic. "Vitamin D appears increase transport of amyloid β across the blood brain barrier (BBB) by regulating protein expression, via the vitamin D receptor, and also by regulating cell signaling via the MEK pathway,” Professor Terasaki explained. “These results lead the way towards new therapeutic targets in the search for prevention of Alzheimer's disease."
Calorie restriction in older mice prevents birth defects in offspring
A report published online on July 5, 2011 in the Proceedings of the National Academy of Sciences describes the discovery of researchers at Massachusetts General Hospital of a protective effect for calorie restriction against damage chromosomes that cause infertility in older mothers and birth defects in their offspring.
In earlier research, Jonathan Tilly, PhD and his associates observed that female mice given low calorie diets during adulthood maintain their fertility into advanced ages. For the current study, three month old female mice were divided to receive unlimited food until they reached one year of age or seven months of a calorie restricted diet followed by free feeding until the study’s conclusion.
While mice that had no restrictions on feeding underwent a decline in the number and quality of eggs released during ovulation, animals that received calorie restricted diets released eggs resembling those of healthy young females. Eggs from non-restricted animals were shown to have chromosome damage, clumping of mitochondria, and a decline in adenosine triphosphate (ATP), the body’s energy molecule. "We found that we could completely prevent, in a mouse model, essentially every aspect of the declining egg quality typical of older females," stated Dr Tilly, who is a professor of Obstetrics, Gynecology & Reproductive Biology at Harvard Medical School. "We also identified a gene that can be manipulated to reproduce the effects of dietary caloric restriction and improve egg quality in aging animals fed a normal diet, which gives us clues that we may be able to alter this highly regulated process with compounds now being developed to mimic the effects of caloric restriction."Dr Tilly added that the finding could one day benefit older women who wish to conceive, as well as help to prevent chromosomal disorders in children.
High folate intake associated with lower, not higher, colorectal cancer risk
The July, 2011 issue of the journal Gastroenterology reports the conclusion of American Cancer Society (ACS) researchers of a reduced risk of colorectal cancer in association with diets that contain higher amounts of the B vitamin folate. The finding contradicts recent speculation that consuming additional folate via food fortification or supplements could increase the risk of the disease.
For the current study, Victoria Stevens, PhD and her associates evaluated data from 43,512 men and 56,011 women enrolled in the Cancer Prevention Study II Nutrition Cohort. One thousand twenty-three participants were diagnosed with colorectal cancer from 1999 to 2007: a period that followed the mandatory fortification of grain products with folic acid to prevent specific birth defects.
High intake of folate and folic acid was found to be associated with a 19 percent reduction in the risk of colorectal cancer compared to low intake. Although no effect on risk was found between 1999 to 2001, high folate consumption was associated with a lower risk from 2002 to 2007.The study is the first to examine the association of colorectal cancer risk with folate during a follow-up period that occurred entirely after the implementation of food fortification with folic acid in the United States. "While folate fortification has been a public health success in reducing the risk of neural tube defects, the potential for an increase risk of cancer has been legitimate," stated Dr Stevens, who ACS’ is strategic director of laboratory services. "Our study population included many participants who consumed these very high levels of folate and we found no increased risk of colorectal cancer in these individuals. Nonetheless, one randomized clinical trial failed to show folate supplementation reduced the risk of adenomas, the noncancerous colon polyps that can become cancerous, so we need to continue to investigate the influence of folate on cancer development in high risk populations as well as potential differences in the action of natural and synthetic form of this vitamin."
Resveratrol may prevent sedentary lifestyle effects
An article published online on June 29, 2011 in the FASEB Journal reveals yet another benefit for resveratrol, a polyphenol found in red wine and grapes. The current research suggests that resveratrol could help protect against the adverse effects of weightlessness during space flight as well as those caused by a sedentary lifestyle, which has been linked to cardiovascular disease, obesity and other health conditions.
“Long-term spaceflight induces hypokinesia and hypodynamia, which, along microgravity per se, result in a number of significant physiological alterations, such as muscle atrophy, force reduction, insulin resistance, substrate use shift from fats to carbohydrates, and bone loss,” Stéphane Blanc of the University of Strasbourg in France and colleagues write. “Each of these adaptations could turn to serious health deterioration during the long-term spaceflight needed for planetary exploration.”
The research team tested the effects of resveratrol in rats undergoing simulated weightlessness. While animals that did not receive resveratrol experienced a reduction in soleus muscle mass and strength, bone mineral density and resistance to breakage, as well as the development of insulin resistance, treatment with resveratrol protected against these conditions.
"There are overwhelming data showing that the human body needs physical activity, but for some of us, getting that activity isn't easy,” commented FASEB Journal Editor-in-Chief Gerald Weissmann, MD. “A low gravity environment makes it nearly impossible for astronauts. For the earthbound, barriers to physical activity are equally challenging, whether they be disease, injury, or a desk job. Resveratrol may not be a substitute for exercise, but it could slow deterioration until someone can get moving again.""If resveratrol supplements are not your cup of tea, then there's good news,” he added. “You can find it naturally in red wine, making it the toast of the Milky Way."