Antioxidants Articles
Supplements for men and women over 50 may improve diet
deficiency
Scientists now believe that free radicals are causal factors in
nearly every known disease
Antioxidants slow age-related impairments in dogs
New Obesity Study Supports Antioxidant Power
Antioxidant Supplements Decease Risk of Heart Disease
Antioxidant Combo Speeds Up
Wound Healing
New Data Finds Antioxidant Combo Decreases Smokers' Cancer Risk
Antioxidant Supplements May
Reduce Risk of Cardiovascular Diseases in Diabetic Patients
Antioxidants in Fruits and
Vegetables May Decrease Stroke Risk
Genes in the Brain Begin to Deteriorate, As Early as Age 40
Nutraceutical: Antioxidants and zinc
Antioxidants and Physical Performance in Elderly Persons
Vitamins Combat Age-Related Blindness
Duke University Study Shows
Positive Results For Antioxidant Users
Antioxidants May Offer Brain Cell Protection
Antioxidants May Protect Against Ozone Pollution
Dietary Antioxidants Help Prevent Alzheimer's
Reversing a long-standing anti-vitamin policy
Raw Material Research
AMERICAN JOURNAL OF EPIDEMIOLOGY
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Supplements for men and women over 50 may improve diet deficiency
Men and women over the age of 51 who regularly take dietary supplements are more likely to get adequate amounts of several vitamins and minerals than those who do not, a new study in the Journal of the American Dietetic Association states.
Researchers also found that a substantial portion of people in this age range do not get enough vitamins and minerals from their diet alone and the use of supplements is necessary.
The study, comprising of 4,384 adults, (1,777 daily supplement users, 428 infrequent users and 2,179 nonusers.) found that fewer than half took supplements daily. Those who did met recommended levels for vitamins A, B and C as well as iron, folate, and zinc,
Researcher Rhonda Sebastian from the US Department of Agriculture said: "These widespread inadequacies should be considered when developing recommendations for supplement use for clients in this age group."
Sebastian and her team found that from diet alone a significantly smaller proportion of supplement users than nonusers had intakes below the estimated average requirement (EAR) for vitamins A, B-6, and C; folate; zinc; and magnesium. Less than half of both users and nonusers met the EAR for folate, vitamin E, and magnesium from food sources alone.
Supplements improved the nutrient intake of older adults, with more than 80 per cent of users meeting the EAR for vitamins A, B6, B12, C, and E, folate, iron, and zinc, but not magnesium, the researchers found.
However, some supplement users, particularly men, exceeded tolerable upper intake levels for iron and zinc and a small percentage of women exceeded the upper intake level for vitamin A, they added.
Overall, supplements improved the nutrient intake of older adults and they concluded that a large "proportion of older adults do not consume sufficient amounts of many nutrients from foods alone. Supplements compensate to some extent, but only an estimated half of this population uses them daily.
"Modifying dietary attitudes may result in a higher rate of supplement use in this at-risk population."
Source: Journal of the American Dietetic Association
Older Adults Who Use Vitamin/Mineral Supplements Differ from Nonusers in Nutrient Intake Adequacy and Dietary Attitudes
doi:10.1016/j.jada.2007.05.010
Authors: Rhonda Sebastian, Linda Cleveland, Joseph Goldman, Alanna Moshfegh.
www.nutraingredients.com 9/18/2007
Scientists now believe that free radicals are causal factors in nearly every known disease.
By controlling free radicals; antioxidants can influence how fast and how well we age. More than 70% of Americans will die prematurely from diseases caused by or compounded by deficiencies of antioxidants. It is virtually impossible to get the optimal amount of antioxidants through food alone.
Dr. Lester Packard, University of California Berkeley
Regarded as the world's foremost antioxidant research scientist
The Natural Products Association, along with others in the science community disputed the conclusions of a new meta-analysis appearing in the February 28 edition of the Journal of the American Medical Association (JAMA) suggesting that the use of antioxidants might increase mortality risk, saying that the study was scientifically misleading and that most clinical research continues to show that antioxidants are safe and beneficial.
"Despite the authors' contention, this analysis is assessing mortality of at-risk and diseased populations - versus a healthy population - in prevention trials. The risk of mortality must be attributed to the appropriate population studied, those with an existing health condition, which it isn't in this case. Instead, those findings are generalized to a healthy general population, which is wrong on many levels," said Daniel Fabricant, Ph.D., vice president of scientific affairs for the Natural Products Association. "But what's most troubling is that people who are safely and beneficially taking vitamins might stop, which may actually put their health at greater risk."
Fabricant also expressed concern that most consumers, who are daily confronted with seemingly contradictory research findings, may understandably become confused and skeptical about such information.
"Just yesterday, for instance, a group of Swedish researchers concluded that vitamin A may help reduce some risks of stomach cancer," said Fabricant. "And ironically, this same medical journal has released a stream of studies suggesting the health benefits of antioxidants; from reduced risk of Alzheimer's disease and macular degeneration, to helping improve immune functioning in patients with HIV spectrum disease."
Other points to be considered in the context of this analysis follow:
- If a true mortality risk was to have become apparent in any of these clinical studies using antioxidants, the study would have been halted. None were. Using these same studies to now draw different conclusions is an indictment of those researchers who conducted the original study and never observed the same outcome or halted the trial.
- Nearly 160 million people in North America and Europe use the attributed supplements. If antioxidants were a significant public health risk, as the authors speculate, it would have become clearly apparent by now. This is obviously not the case: the negative effect they refer to has not been seen in the population.
- The initial hurdle for performing a clinically meaningful meta-analysis is the criteria for how similar the studies must be in order to be included in the meta-analysis. The more similar the studies, the more valid the meta-analysis. In this instance the studies are very divergent and the conclusion of the meta-analysis is not consistent with the findings of the actual clinical studies. In addition, large controlled clinical studies on antioxidants exist and the data from those studies will be much more meaningful and relevant than a piecemeal meta-analysis like this.
This new analysis has drawn criticism from both inside and outside the dietary supplements industry concerning the methodology applied, and the conclusions drawn.
The most prevalent criticism of the study has come from the diverse nature of the studies pooled together, described by one industry expert as comparing "apples and oranges".
Moreover, Meir Stampfer, a professor of nutrition and epidemiology at the Harvard School of Public Health who was not connected to the meta-analysis, told the Associated Press that the studies reviewed were too different to be able to pool them together.
"This study does not advance our understanding, and could easily lead to misinterpretation of the data," Stampfer told the AP.
"Most trials investigated the effects of supplements administered at higher doses than those commonly found in a balanced diet, and some of the trials used doses well above the recommended daily allowances and even above the tolerable upper intake level," said the reviewers.
Many of the studies included only subjects already classified as suffering from certain diseases. Indeed, only two of the studies classified as "low bias" were carried out in the 'general population'.
When taken in their entirety, antioxidants were found to have no significant effect on mortality. This result did not hold however when the reviewers looked at the nutrients singly and removed studies that they classed as having a 'high bias' in favour of the antioxidants.
Moreover, Andrew Shao, Ph.D., CRN's vice president, scientific and regulatory affairs said that the combined studies were far too diverse and different in terms of dosage, duration, study population and nutrients tested that the results of the analysis were "compromised".
Additionally, Dr. Shao noted that most of the trials included in the meta-analysis tested for secondary prevention, looking at how a nutrient works in diseased populations, instead of primary prevention studies in healthy populations.
"Combining secondary prevention and primary prevention trials and then making conclusions for the entire population is an unsound scientific approach," said Shao. "Additionally, many of the trials had limitations, including the expectation that a simple antioxidant vitamin could be expected to overturn serious illness, such as cancer or heart disease. These trials likely statistically skewed the results."
Daniel Fabricant, vice president of scientific affairs for Natural Products Association (NPA), another US-based trade association, supported this view.
"Despite the authors' contention, this analysis is assessing mortality of at-risk and diseased populations - versus a healthy population - in prevention trials. The risk of mortality must be attributed to the appropriate population studied, those with an existing health condition, which it isn't in this case. Instead, those findings are generalized to a healthy general population, which is wrong on many levels," said Fabricant.
"But what's most troubling is that people who are safely and beneficially taking vitamins might stop, which may actually put their health at greater risk."
Fabricant also stated that if a true mortality risk had been apparent in any of these clinical studies using antioxidants, the study would have been halted, but none were.
"Nearly 160 million people in North America and Europe use the attributed supplements. If antioxidants were a significant public health risk, as the authors speculate, it would have become clearly apparent by now," he said. "This is obviously not the case: the negative effect they refer to has not been seen in the population."
Source: Journal of the American Medical Association
February 28 2007, Volume 297, Pages 842-857
"Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis"
Authors: G. Bjelakovic; D. Nikolova; L. Lotte Gluud; R.G. Simonetti; C. Gluud
The Antioxidant Miracle, Lester Packard, Ph.D
www.healthy.net
Antioxidants slow age-related impairments in dogs
A University of Toronto study involving beagles indicates that cognitive stimulation may boost the effects of a diet rich in antioxidants in combating the loss of learning ability with advanced aging.
The effectiveness of two interventions, dietary fortification with antioxidants and a program of behavioral enrichment, was assessed in a longitudinal study of cognitive aging in beagle dogs. The results of this study of four groups of beagles, over a two-year period, are published in the January 2005 issue of Neurobiology of Aging.
In October 2003, a separate study conducted at the University of Toronto showed that old dogs that were on diet fortified with antioxidants such as vitamin E, vitamin C, and beta-carotene performed better on a variety of cognitive tests than dogs that were not on the diet.
"Although we found that not all cognitive functions respond to antioxidant treatment, our data suggests that antioxidants play an important role in preventing or slowing age-related cognitive impairments," said Dr Dwight Tapp.
In the latest study, one group of elderly dogs was fed a regular diet combined with regular experience. The second group received a regular diet and enriched experience; the third group an enriched diet and regular experience; and the fourth group both an enriched diet and an enriched experience.
The results suggest that behavioral enrichment or dietary fortification with antioxidants over a long-duration can slow age-dependent cognitive decline, and that the two treatments together are more effective than either alone in older dogs.
"We were really surprised just how clear-cut the benefit is of using a combined therapy," said lead investigator and psychology professor Bill Milgram.
"Since humans and dogs have many biological and behavioral parallels, I predict similar results would be attained in people," he added.
Like humans, dogs lose some of their ability to learn new information as they get older and suffer from both long-and short-term memory lapses.
January 2005,(77-90) Neurobiology of Aging
N. W. Milgram, E. Head, S. C. Zicker, C. J. Ikeda-Douglas, H. Murphey, B. Muggenburg, C. Siwak, D. Tapp and C. W. Cotman
www.nutraingredients.com
New Obesity Study Supports Antioxidant Power
New findings from Japanese researchers could help society understand the mechanistic role of obesity in the metabolic syndrome and could eventually help stem the obesity epidemic.
Metabolic syndrome is a condition marked by a combination of abdominal obesity, high blood pressure, poor blood sugar control, low HDL 'good' cholesterol and high blood fats. The constellation of health conditions increases the risk of developing Type 2 diabetes and heart disease.
Classed as an epidemic by the UN-backed World Health Organization, at least 171 million people worldwide suffer from diabetes, a figure likely to more than double to 366 million by 2030.
IIichiro Shimomura and colleagues from Osaka University, Japan, claim that fat cells of obese mice produce increased levels of toxic oxygen molecules known as reactive oxygen species (ROS) as well as the enzyme NADPH oxidase.
The scientists found that treatment of these mice with apocynin – an antioxidant that inhibits NADPH oxidase – reduced ROS production in fat cells, restored adipocytokine production to normal, improved diabetes, and reduced the levels of fat present in the blood and liver.
Although it is too early to suggest that taking antioxidants may counter the development of obesity-associated metabolic syndrome, ‘the steps leading to excess ROS generation may represent a potentially useful therapeutic target,’ say the researchers, who reported their findings in the 15 December issue of the Journal of Clinical Investigation.
The role of antioxidants in preventing health conditions is widely documented, and gaining pace with each new study published.
Linked in some research to reduced risk for cancers, especially prostate cancer, the health-boosting carotenoid antioxidant lycopene has attracted significant attention in recent years. A recent report on the $348.5 million (€291.4m) carotenoid market set to grow to €349.3 million in 2010 from market analysts Frost & Sullivan revealed that the European food and health industry, has ‘under-utilised’ the nutraceutical properties of carotenoids, and consumers are still unaware of their health benefits.
Frost & Sullivan claims that carotenoids are still used primarily as a colouring agent for the food and feed industries. Consumers in most European regions are unaware of their use as a food fortifier and this poor level of public awareness about the health benefits of carotenoids is expected to stifle market growth in the short term.
Nutraingredients.com
16/12/2004
Antioxidant Supplements Decease Risk of Heart Disease: Epidemiologic Studies Not Trumped by Clinical Trials
WASHINGTON, D.C., August 4, 2004-Epidemiologic studies, including results from at least four large cohorts, indicate that among the healthy population the long-term use of antioxidant supplements, specifically vitamin E and vitamin C, helps protect against heart disease. "It is puzzling how the American Heart Association's nutrition committee could recommend against the use of antioxidant supplements for primary prevention of heart disease, in the face of evidence such as this," said Annette Dickinson, Ph.D., president of the Council for Responsible Nutrition. "Even if recent secondary intervention trials have been disappointing, those results do not trump the epidemiological data on primary prevention." (Primary prevention is avoiding or delaying heart disease in healthy people; secondary prevention is avoiding a second heart attack or stroke in people who have already had one.)
A study of more than 80,000 nurses found that women who took vitamin E supplements for more than two years had a 41% reduction in risk of major coronary disease. (Stampfer 1993) A later study of the nurses' cohort found that women who took vitamin C supplements had a 27% reduction in risk of coronary heart disease. (Osganian 2003) A study of almost 40,000 male health professionals (mostly dentists) found that men who took vitamin E supplements for at least two years had a 37% reduction in risk of coronary disease. (Rimm 1993) A study in more than 11,000 elderly people found that those who used vitamin E supplements had a 47% reduced risk of coronary disease mortality, and those who used supplements of both vitamin E and vitamin C had a 53% reduced risk of coronary mortality. (Losonczy 1996) These are large and important effects. The exception is a study of almost 35,000 post-menopausal women that found a protective effect of vitamin E from conventional foods, but not from supplements ñ but the authors noted that relatively few of the women used vitamin E and they had no information on the duration of use. (Kushi 1996)
The American Heart Association's science advisory recognizes that the epidemiological data is compelling, but implies that such evidence applies only to the intake of antioxidants from conventional foods, and not from supplements. (AHA 2004) This is not the case, since the studies cited above specifically examined supplemental intake, and four of the five reported significant benefits in the primary prevention of heart disease associated with the use of antioxidant supplements in healthy populations.
What is the best advice for consumers? For overall health maintenance as well as potential protection against some chronic diseases, the Council for Responsible Nutrition recommends consuming the best possible diet, with lots of fruits and vegetables and two servings of fish per week; getting regular exercise; and supplementing those healthy habits with what UCLA's David Heber, M.D., has called the "basic four" nutritional supplements: a multivitamin, extra calcium, extra vitamin E, and extra vitamin C. (Heber 2001)
REFERENCES
AHA Science Advisory: Antioxidant vitamin supplements and cardiovascular disease. Circulation 2004; 110:637-641.
Heber D. What Color is Your Diet? Regan Books (HarperCollins Publishers), New York, NY, 2001.
Kushi L, et al. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. NEJM 1996; 334:1156-1162.
Losonczy KG, et al. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the established populations for epidemiologic studies of the elderly. Am J Clin Nutr 1996; 64:190-196.
Osganian S, et al. Vitamin C and risk of coronary heart disease in women. J Am Coll Cardiology 2003; 42:246-252.
Rimm EB, et al. Vitamin E consumption and the risk of coronary heart disease in men. NEJM 1993; 328:1450-1456.
Stampfer MJ, et al. Vitamin E consumption and the risk of coronary disease in women. NEJM 1993; 328:1444-1449.
www.crnusa.org
Antioxidant Combo Speeds Up Wound Healing
A dietary supplement containing vitamin C and plant extracts helped speed up wound healing in a new study on plastic surgery patients.
The researchers from the University of Texas found that patients taking the supplement recovered from a plastic surgery procedure like a facelift three days faster than those taking placebo.
The results could be a result of the antioxidant activity present in all four ingredients in the supplement although the scientists could not tell which ingredient or combination is the active ingredient.
"We were completely surprised that this combination of supplements actually reduced the recovery time for our patients," said Rod Rohrich, president of the American Society of Plastic Surgeons and co-author of the study.
Rohrich and colleagues found patients healed 17 per cent faster by taking the mixture of bromelain, vitamin C, rutin and grape seed extract.
"Previously, it would generally take 18 days for a patient to recover from a plastic surgery procedure, such as a facelift," said co-author James Chao. "By taking these supplements right after the procedure, patients can fully heal in just 15 days.
"The supplement could bring cost savings by cutting down on healing time as well as medicine for increasing numbers of plastic surgery patients. The results also demonstrate the potential benefits of the supplement ingredients for other types of wounds.
In the study, published in the July issue of Plastic and Reconstructive Surgery (114, issue 1, 237-244), 26 healthy volunteers took part in a randomized, crossover, placebo-controlled, clinical trial consisting of two phases, each lasting 21 days. In the first phase, subjects were subjected to a 3-mm forearm skin biopsy and randomly received a placebo or oral supplement (four capsules per day for seven days).
After a two-week washout period, a second biopsy was performed to start the second phase, with each subject receiving the respective placebo or supplement capsules. Digital photographs were taken during wound healing in both phases and analyzed for wound areas and perimeters.
More than 80 per cent of the participants benefited from taking the supplements during the early phase of the healing process, which accelerated the soft-tissue wound healing compared with subjects who received the placebo.
The researchers said they observed decreased redness in the wound for subjects receiving the supplement, indicating that the supplement cocktail more than likely changed the inflammatory process. As with all wounds, if the wound stays inflamed longer, it takes longer to heal.
All of the ingredients included in the mixture, (made by Enzymes Inc, based in Parkville, Missouri) are antioxidants, which enhance cellular stability and decrease swelling. Bromelain is an anti-inflammatory agent that helps heal minor injuries, including sprains, strains and muscle injuries, and has been found to dramatically reduce postoperative swelling.
Preliminary studies also suggest that vitamin C supplements in non-deficient people can speed healing of various types of wounds and trauma, including surgery, minor injuries, herniated intervertebral disks and skin ulcers.
In addition there is evidence that both rutin and grape seed extract helps the vitamin C's activity in cells. A study at Ohio State University in 2002 found grape seed extract to help skin wounds heal faster and with less scarring, by helping regenerate damaged blood vessels and increasing the amount of free radicals in the wound site.
However Dr Rohrich warned: "This study is a bridge towards discovering if any of these individual supplements have merit separately or combined together. Only through further study can we discover how these antioxidants work to shorten recovery time for patients."
13/07/2004
NutraIngredients.com
New Data Finds Antioxidant Combo Decreases Smokers' Cancer Risk
Smokers taking a wide range of antioxidants through their diet appear to have a lower risk of lung cancer, according to a recent study.
The results counter the findings of a trial carried out in the 90s, the Finnish ATBC study, which found an increased risk of the disease for smokers with high beta-carotene intake.
In the new study, researchers from Yale University and other US institutes together with colleagues from the National Public Health Institute in Helsinki, Finland analyzed the same data but looked at the total intake of antioxidants, including selenium, vitamin E, vitamin C as well as carotenoids and flavonoids, rather than one single antioxidant.
At baseline (1985-1988), 27,111 Finnish male smokers aged 50-69 years completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months. A total of 1,787 incident cases of lung cancer were identified during a follow-up period of up to 14.4 years (1985-1999).
Writing in the 1 July issue of the American Journal of Epidemiology (160:68-76), the researchers report that smokers in the top quintile of dietary antioxidant intake had a 16 per cent lower risk of lung cancer compared to those with the lowest intake.
Smokers who ate large amounts of meat had a 25 per cent decrease, despite red meat having a high oxidative effect.
The Vitality Council, a Danish organization set up by the Danish Society for Orthomolecular Medicine and producers and distributors of vitamins and minerals to inform consumers and health professionals about new research, said the results are of "great importance, because they are sourced from the same ATBC study, which has been one of the most outspoken arguments to warn against antioxidants".
It noted that two other larger studies have found the risk of lung cancer decreased up to as much as 32 per cent and 68 per cent.
The researchers add in a commentary that the original ATBC study results have been due to the fact that the smokers did not get a combination of vitamins but were given beta-carotene alone. They recommend smokers take a variety of antioxidants as a protection against cancer.
NutraIngredients.com
09/08/2004
Antioxidant Supplements May Reduce Risk of Cardiovascular Diseases in Diabetic Patients
BACKGROUND
Diabetic patients are two to four times more likely to die from cardiovascular diseases compared with people who do not have diabetes. This increased risk cannot be explained by conventional risk factors, such as elevated cholesterol levels. Considerable evidence indicates that free-radical-induced "oxidative stress" contributes to the higher risk of cardiovascular disease, and studies suggest that antioxidant supplementation may be helpful.
RESEARCH
In this review article, researchers described the relationship between oxidative stress and cardiovascular disease in diabetes. For example, people with diabetes tend to have lower blood levels of antioxidants compared with nondiabetics. The resulting oxidative stress leads to alterations in low-density lipoprotein (LDL) cholesterol, blood coagulation, and blood vessel function, each contributing to an increased risk of cardiovascular disease.
RESULTS
Clinical studies have found that supplements of several individual antioxidants--vitamin E, alpha-lipoic acid, and vitamin C--can reduce the risk of complications and death from diabetes. For example, one study of patients with end stage renal disease (42 percent of the subjects were diabetic) found that natural vitamin E supplements (800 IU daily) lowered the risk of major cardiovascular events, including heart attack and stroke, by 54 percent. Similarly, supplemental alpha-lipoic acid (600 mg daily) significantly improved nerve function in diabetic patients with neuropathy. Still other studies have found that vitamin C supplementation (500 mg daily) reduced blood pressure in nondiabetic patients with hypertension.
IMPLICATIONS
The researchers concluded, "Compelling evidence points to the role of oxidative stress in diabetic vasculopathies.However, further research is still needed to better understand the mechanisms by which different antioxidants may aid in the prevention of vascular dysfunction in diabetic patients.
"Vega-Lopez S, Devaraj S, Jialal I. Oxidative stress and antioxidant supplementation in the management of diabetic cardiovascular disease. Journal of Investigative Medicine, 2004;52:24-32.
Antioxidants in Fruits and Vegetables May Decrease Stroke Risk
Sufficient blood levels of carotenoids, a family of antioxidants in fruits and vegetables, might reduce the risk of ischemic stroke, according to a study published today in the rapid access issue of Stroke: Journal of the American Heart Association.
An ischemic stroke is caused by a blood clot and is the most common type of stroke.
Fruit and vegetable intake has long been associated with a lower risk of ischemic stroke, said study author Jing Ma, M.D., Ph.D., assistant professor of medicine, Brigham and Women's Hospital, Harvard Medical School, Boston. Researchers investigated which antioxidants in fruits and vegetables might have this positive effect.
The Physicians' Health Study involved 22,071 U.S. male physicians, 68 percent of whom provided blood samples at the start of the study in 1982. Among the 15,000 who didn't have cardiovascular disease at the beginning of the study, 297 had an ischemic stroke during the study's 13-year follow-up.
Analyzing blood samples among stroke patients, researchers measured levels of antioxidants, including carotenoids (vitamin A family, including alpha-carotene, beta-carotene, lycopene, lutein and beta-cryptoxanthin) and tocopherols (vitamin E). They then compared their findings to the blood levels of an equal number of men who did not have stroke.
They found that men who were in the lowest 20 percent quintile (bottom fifth) for carotenoid levels of alpha-carotene, beta-carotene and lycopene had the highest risk of ischemic stroke.
Men who were above the second through fifth quintiles were at a 40 percent lower risk of developing ischemic stroke during the 13 years than men in the lowest quintile, Ma said.
Once blood levels moved beyond that 20 percent threshold of carotene, the stroke protection benefit did not seem to increase with higher levels, Ma said.
The carotenoid level could have been the result of these men eating fruits and vegetables or taking antioxidant supplements.
The observational study shows an association between fruit and vegetable intake and stroke risk, but did not prove that eating fruits and vegetables caused the lower risk.
The results of this study support a diet high in fruits and vegetables to reduce ischemic stroke risk, she said.
Co-authors are A. Elizabeth Hak, M.D., Ph.D.; Calpurnyia B. Powell, B.S.; Hannia Campos, Ph.D.; J. Michael Gaziano, M.D.; Walter Willett, M.D., Dr.P.H.; and Meir J. Stampfer, M.D., Dr.P.H.NR04-1264 (Stroke/Ma)
Genes in the Brain Begin to Deteriorate, As Early as Age 40
Harvard University researchers found that 20 genes critical for learning and memory begin to decline in function as early as age 40, pointing the way for further research aimed at tackling the mental infirmities that come with growing old.
The Harvard work, released yesterday in the online edition of Nature, is the first major study to use a "genetic signature" to study brain-function decline in normal aging.
A genetic signature is a recent scientific innovation that measures the activity level of thousands of genes -- determining which are working hard, which are minimally active, and which are idle in controlling the production of proteins, which are the main actors in all microscopic bodily functions, including work performed by the brain.
The researchers studied well-preserved brain tissue from 30 people, aged 26 to 106 at the time of death. The changes they found occurred in a wide variety of genes, with functions that range from regulating sleep to metabolizing fat. But most interesting was a marked decline in function among 20 genes involved in learning, memory and the plasticity, or flexibility, of brain function. As the subjects aged, these genes became damaged, reducing their effectiveness. "Some genes begin to decline much earlier than expected, as early as the early 40s," says senior author Bruce Yanker, a professor of neurology and neuroscience at Harvard Medical School and Children's Hospital in Boston.
The Harvard researchers believe the damage is caused by exposure to toxins, including unstable molecules called free radicals. Free radicals are created both by the body's own energy-producing processes and by exposure to environmental hazards. Antioxidants such as vitamins C and E are believed to protect the body against the ravages of free radicals. Antioxidants could, in theory, help the brain protect itself from age-related damage, Dr. Yanker says, but there's still no proof that it would work.
In the older brain samples, the researchers found that genes whose job is to protect and repair neurons from damage had been working overtime. That compensatory activity may delay the effects of the damage, and could explain damage to cognitive function often doesn't show up until later in life, and why some individuals retain their intellectual acumen longer than others. The effectiveness of the compensatory activity "may be a function of genetics, and lifestyle, probably a combination of both," Dr. Yanker says.
Their search was limited to 11,000 of the body's 30,000 genes because those were the only genes available on the microchip used to perform the computerized search -- the best available at the time the work began two years ago. The researchers found that 4% of the 11,000 genes changed in activity with age. Some became less active, and others stepped up their activity. The changes began in the early 40s and varied widely from person to person until age 71. Over that age, the gene activity pattern was largely the same from one person to the next.
No Immediate Cures
The findings don't in themselves offer immediate cures to age-related mental decline, Dr. Yanker says, but are a "treasure trove" of information that will help researchers find the most promising avenues of study.
The research "adds to our understanding of the genetic factors that might contribute to memory loss," says Gary Small, director of the Center on Aging at the University of California, Los Angeles. He adds that the fact that the genetic changes start early "emphasizes how important it is to begin lifestyle changes early." Dr. Small is researching the effect of lifestyle changes, such as a healthy diet and exercise, on age-related declines in cognitive functions.
In his work, Dr. Small found that as little as two weeks on a program that includes exercise, stress reduction, and a healthy diet with antioxidants such as Japanese green tea, appears helpful for brain function. He found that subjects required less cerebral effort -- as measured by brain scans of neuronal activity -- to complete the same mental tasks than they did before they began the healthy program. Healthy diets are already widely believed to reduce fat buildup, which can increase the risk of strokes, Dr. Small says. But good nutrition also may have other, not yet understood effects on gene function.
Another possible approach is to try to mitigate the gene damage through medications. The Harvard researchers found that a very promising area of study is an enzyme used by the body to repair DNA damage, called oxoguanine DNA glycosylase. The enzyme was already known to the scientific community, but the Harvard researchers found that it was very effective in repairing genetic damages in brain neurons placed in a petri dish.
"If one had, for example, a drug to stimulate the activity of this enzyme, one might be able to repair the DNA" and slow the mental decline that happens with age, Dr. Yanker says.The research, funded by the National Institutes of Health and anonymous philanthropic donations, was done using a gene chip from Affymetrix Inc., of Santa Clara, Calif. The Harvard researchers are repeating the study with all 30,000 human genes on a newer chip from Affymetrix. The scientists also plan to study gene changes in people with Alzheimer's disease, and compare them to the changes found in normal aging.
THE WALL STREET JOURNAL
June 10, 2004; Page D1
Nutraceutical: Antioxidants and zinc
Indication/Goal
Evaluating age-related eye disease study (AREDS) public health impact
Source
Arch Opthalmol, November 2003;121(11):1621-4
Research
Researchers estimated the potential public health impact findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced macular degeneration (AMD) during the next five years in the US. The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dosage nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during five years if those at risk were to take a supplement such as that used in AREDS.
Results
An estimated eight million persons at least 55 years old in the US have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next five years. If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the US would be considerable during the next five years.
Antioxidants and Physical Performance in Elderly Persons
The Invecchiare in Chianti (InChianti) study1,2,3
Matteo Cesari, Marco Pahor, Benedetta Bartali, Antonio Cherubini, Brenda WJH Penninx, G Rhys Williams, Hal Atkinson, Antonio Martin, Jack M Guralnik and Luigi Ferrucci
1 From the Sticht Center on Aging, Wake Forest University Health Sciences, Winston-Salem, NC (MC, MP, BWJHP, and HA); the Laboratory of Clinical Epidemiology, Italian National Research Council of Aging, Geriatric Department, Florence, Italy (BB); the Department of Gerontology and Geriatrics, University of Perugia, Perugia, Italy (AC); the Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ (GRW); the Human Nutrition Research Center on Aging, Tufts University, Boston (AM); the Epidemiology, Demography, and Biometry Program, National Institute on Aging, Bethesda, MD (JMG); the Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore (LF).
Background
Muscle strength and physical performance in old age might be related to the oxidative damage caused by free radicals.
Objective
The objective was to assess the correlation of plasma concentrations and daily dietary intakes of antioxidants with skeletal muscle strength and physical performance in elderly persons.
Design
This study is part of the Invecchiare in Chianti (InCHIANTI) study, which was conducted in 986 Italians aged =" src="/math/ge.gif" border=065 y. Physical performance was assessed on the basis of walking speed, ability to rise from a chair, and standing balance. Knee extension strength was assessed with a hand-held dynamometer. The European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire was used to evaluate the daily dietary intakes of vitamin C, vitamin E, ß-carotene, and retinol. Plasma - and -tocopherol concentrations were measured. Adjusted linear regression analyses were used to calculate regression coefficients per SD increase in plasma concentrations and daily dietary intakes.
Results
In adjusted analyses, plasma -tocopherol was significantly correlated with knee extension (ß = 0.566, P = 0.003) and the summary physical performance score (ß = 0.044, P = 0.008). Plasma -tocopherol was associated only with knee extension strength (ß = 0.327, P = 0.04). Of the daily dietary intake measures, vitamin C and ß-carotene were significantly correlated with knee extension strength, and vitamin C was significantly associated with physical performance (ß = 0.029, P = 0.04).
Conclusions
Plasma antioxidant concentrations correlate positively with physical performance and strength. Higher dietary intakes of most antioxidants, especially vitamin C, appear to be associated with higher skeletal muscular strength in elderly persons.
American Journal of Clinical Nutrition, Vol. 79, No. 2, 289-294, February 2004
Vitamins Combat Age-Related Blindness
Hundreds of thousands of people could benefit from vitamin supplements shown to help prevent macular degeneration, a condition that is the leading cause of blindness from age 65, a study reported.
In 2001, researchers announced they had found a reduced risk of advanced age-related macular degeneration and vision loss for test subjects who had been given high-dose antioxidant supplements -- vitamins C, E and beta carotene -- as well as zinc or zinc oxide.
In Monday's report, researchers at the Johns Hopkins Medical Institutions in Baltimore tried to estimate how many people in the United States alone would benefit from increasing supplement use.
They concluded there are 8 million Americans at least 55 years old thought to be at high risk for the problem. If all the people at risk took the supplements used in the earlier study, more than 300,000 of them would avoid advanced macular degeneration and any associated vision loss during the next five years, the study said.
"If even half of the individuals at high risk for (the condition) were identified and compliant with the recommended supplement, it is likely that more than 150,000 individuals would avoid vision loss for some time," said the study published in the November issue of the Archives of Ophthalmology.
"These data suggest that the recommendation of such a supplement for these individuals should have a major impact on them as well as on the public health," the authors concluded.
In an editorial commenting on the study published in the same journal, Lee Jampol, a physician at the Northwestern University Feinberg School of Medicine in Chicago, said the supplements should be used "only in patients with intermediate or advanced age-related macular degeneration."
"What about patients who have a strong family history of macular degeneration or who for other reasons believe that they are at risk for the disease and wish to take the (supplement) formulation prior to the development" of intermediate or advances cases of the problem, he asked.
"It appears appropriate to eat a diet rich in fruits and (especially green) vegetables, to supplement with a multivitamin and to undergo periodic ophthalmic examinations for the development of" the condition, he added.
CHICAGO, Illinois (Reuters)
Duke University Study Shows Positive Results For Antioxidant Users
A multi-site cooperative study out of Duke University shows that in a group of seniors over 75 years old, "current antioxidant users had a 34%
lower risk of developing cognitive impairment compared with non-antioxidant users...and a 29% lower risk of experiencing cognitive
decline...."
American Journal of Geriatric Pharmacotherapy, Sept 2003, Vol 1, Num 1.
Title: Is antioxidant use protective of cognitive function in the community-dwelling elderly?
Antioxidants May Offer Brain Cell Protection
Alcohol damage may be averted.
Antioxidants, already widely promoted as cancer-fighters, also may help protect the brain from chronic alcohol damage. Chronic alcoholism damages parts of the brain used in learning and memory, but giving rats an antioxidant protected them from the damage, according to researchers working in the US and Spain.
The findings are reported in the June 3rd, 2003, online issue of Proceedings of the National Academy of Science.
Antioxidants are chemicals that inhibit the oxidation of a substance to which they are added. Oxidation can stress or damage cells.
The team, led by Dr. Daniel G. Herrera of Weill Medical College of Cornell University, fed rats a liquid diet containing alcohol for six weeks. They found a 66 percent decrease in the number of new cells in crucial parts of the brain and an increase in cell death of more than 227 percent. But in rats that also received injections of the antioxidant ebselen, the damage to developing cells did not occur, the researchers said.
Those rats had the same brain characteristics as a group that received no alcohol. Alcohol also kills liver cells, and the researchers knew that this could be reduced with the use of antioxidants, Herrera said. They decided to see if the same held for the brain. The antioxidant ebselen was used because it is known to have protective effects in the liver and digestive tract and has few side effects in humans. Finding ways to improve mental function in people, particularly the elderly, might increase positive results of alcohol treatment programs, Herrera said in a statement.
Dr. Antonio Noronha, chief of the neuroscience and behavioral branch of the National Institute of Alcohol Abuse and Alcoholism, said this is the first study to show the effects of antioxidants on chronic alcohol damage. Noronha, who was not part of the research team, said similar findings have been reported in studies at the University of North Carolina, but those focused on binge drinking and used a different antioxidant. The mechanism by which alcohol damages portions of the brain is still not fully understood, he said. Oxidative stress seems to be part of it, and the antioxidants appear to be protective.
Antioxidants May Protect Against Ozone Pollution
Vitamin C and E supplements appear to provide some protection against ozone pollution in young children with asthma, suggests the results of a new study.
Researchers at the National Institute of Public Health in Mexico gave 158 asthmatic children either a placebo or 50 mg of vitamin E and 250 mg of vitamin C per day and observed them for 18 months, carrying out pulmonary function tests twice per week.
The researchers found that the supplements improved forced expiratory volume.
"Our results suggest that supplementation with antioxidants might modulate the impact of ozone exposure on the small airways of children with moderate to severe asthma," wrote the researchers.
Source: I Romieu et al., "Antioxidant Supplementation and Lung Functions Among Children with Asthma Exposed to High Levels of Air Pollutants, "American Journal of Respiratory and Critical Care Medicine 166 (September 1, 2002):703-709
Dietary Antioxidants Help Prevent Alzheimer's
A diet rich in antioxidants may help protect against Alzheimer's disease, according to the results of the Rotterdam Study involving 5,395 people aged 55 and older.
In 1990, researchers determined the participants' intakes of beta-carotene, flavonoids, vitamin C and vitamin E. During the next ten years, participants were screened for Alzheimer's disease; a neurologist, neurophysychologist and magnetic brain imaging confirmed the condition in 146 of the subjects. Compared with participants whose diets provided fewer antioxidants, those with greater vitamin C intake cut their Alzheimer's risk by nearly 30%; those with greater vitamin E intake by up to 43%.
Smokers experienced the greatest risk reduction from antioxidants. Smokers, unlike the overall study population, also reduced their Alzheimer's risk when they consumed more beta-carotene and flavonoids.
Maryanne Engelhart, M.D., director of this population-based prospective cohort study, suggests that by decreasing excess oxidation in the brain, antioxidants may prevent the DNA damage, neuron cell death and build-up of the brain-clogging substance beta-amyloid that typify Alzheimer's disease.
Journal of the American Medical Assoc.
2002 Jun 26;287:3223-9.
Reversing a long-standing anti-vitamin policy
The Journal of The American Medical Association today is advising all adults to take at
least one multivitamin pill each day.
Scientists' understanding of the benefits of vitamins has rapidly advanced, and it now appears that people who get enough vitamins may be able to prevent such common chronic illnesses as cancer,
heart disease and osteoporosis, according to Drs. Robert Fletcher and Kathleen Fairfield of Harvard University, who wrote the new guidelines.
The last time JAMA made a comprehensive review of vitamins, about 20 years ago, it concluded people of normal health shouldn't take multivitamins because they were a waste of time and money. People can get all the nutrients they need from their diet, JAMA advised, adding that only pregnant women and chronically sick people may need certain vitamins. That was at a time when knowledge about vitamins was just beginning to expand. The role that low levels of folate, or folic acid, play in neural tube defects, for instance, was not known, nor was its role as a major risk factor for heart disease.
Researchers hope JAMA's endorsement will encourage more people to reap health benefits of a daily multivitamin. Health experts are increasingly worried that most American adults do not consume healthy amounts of vitamins in their diet, although they may be getting enough to ward off such vitamin-deficiency disorders as scurvy, beriberi and pellagra. Almost 80 percent of Americans do not eat at least five helpings of fruits and vegetables a day, the recommended minimum amount believed to provide sufficient essential nutrients.
Humans do not make their own vitamins, except for some vitamin D, and they must get them from an outside source to prevent metabolic disorders. "It's nice to see this change in philosophy that's saying we can make public-health recommendations based on this really compelling set of data," said Dr. Jeffrey Blumberg, chief of antioxidant research at Tufts University's Jean Mayer USDA Human Nutrition Research Center on Aging. Blumberg said the JAMA recommendations underscore a growing concern among nutrition experts that the recommended daily allowances, or RDAs, for many vitamins are set too low. RDAs essentially were established to prevent symptoms of vitamin-deficiency disorders, he said. But evidence is growing that higher levels of many vitamins are necessary to achieve optimum health, he said.
The National Academy of Sciences, which sets RDAs, is revising its recommendations based on the new evidence. Even people who eat five daily servings of fruits and vegetables may not get enough of certain vitamins for optimum health, Fletcher said. Most people, for instance, cannot get the healthiest levels of folate and vitamins D and E from recommended diets, he said. "All of us grew up believing that if we ate a reasonable diet, that would take care of our vitamin needs," Fletcher said. "But the new evidence, much of it in the last couple of years, is
that vitamins also prevent the usual diseases we deal with every day - heart disease, cancer, osteoporosis and birth defects." Because foods contain thousands of vitaminlike compounds - many not yet identified - that may be important for good health, vitamin supplements should not be a substitute for a wholesome diet, Blumberg said.
Chicago Tribune
By Ronald Kotulak 6-20-02
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Raw Material Research (AMD)
Raw Materials
Antioxidants
Indication
Age-related macular degeneration (AMD)
Source
Archives of Opthalmology, 2001;119:1417-1436
Research: More than 3600 patients, aged 55-80, from 11 medical centers took one of the following supplements or placebo for an average of six years:
(1) a multi-antioxidant containing vitamin C (500 mg), vitamin E (400 IU), beta-carotene (15 mg) daily;
(2) zinc (80 mg) and copper (2 mg)
(3) a combination of the antioxidants above, plus zinc and copper
Results
Patients with the highest risk of advanced AMD experienced the greatest benefits, with the combination of antioxidants and zinc reducing the rate of visual acuity loss by 27%.
In general, the antioxidant/zinc combination reduced the overall risk of AMD by 28%. Antioxidants and zinc each reduced the risk of AMD, but their effect was greater in combination.
Raw Material Research (Asthmatics)
Raw Materials
Antioxidants
Indication
Protecting asthmatics from air pollution
Source
Archives of Environmental Health, 2001;56:242-249
Research
Researchers studied the effect of supplements containing 400 IU of vitamin E and 500 mg of vitamin C versus placebo on 17 adult asthmatics for five weeks. The subjects' lung function was measured after four weeks, using three standard tests, following ozone exposure during mild exercise on a treadmill. The experiment was then repeated after another week.
Results
After taking the antioxidants, subjects tolerated the ozone with considerably less breathing difficulty compared to placebo and, sometimes, experienced improvements in lung function.
Raw Material Research (Alzheimer’s disease)
Raw Material
Antioxidant Vitamins
Indication
Reduction in possibility of Alzheimer's disease.
Source
Age and Aging 2001;30:235-241
Research
Researchers measured levels of antioxidants and free radicals in 20 patients with Alzheimer's disease and 23 elderly people without the disease.
Results
People with Alzheimer's disease had lower blood levels of vitamins E and A and higher levels of malondialdehyde, a marker of free radicals.
Vitamins C And E Supplements Protect Lungs
Researchers have found that daily doses of vitamin C and E counteract the negative, inflammatory effect on lungs from the pollutant ozone. Previous studies have shown that even low levels of ozone have significant effects on lung function, as little as one hour after exposure. These effects have been previously studied by researchers exercising athletes indoors, under laboratory conditions.
Research teams feel that the antioxidants protect the lungs by reducing the lung's inflammatory response to the pollutants and ozone. Vitamin E and antioxidants are believed to have anticancer effects as well as heart protective benefits.
American Journal of Epidemiology, 1999 |
