Phytochemicals of Antioxidants

Researcher Focuses on Pros, Cons of Antioxidants from Fruits and Vegetables

Nutrition: It's not just the four basic food groups any more.

Researcher Dr. Susanne Mertens-Talcott of Texas A&M University is looking into how plant-based phytochemicals, including antioxidants and herbal supplements, can be useful in the promotion of health and prevention of chronic diseases.

This field is still growing. In the U.S. more than $20 billion was spent on dietary supplements in 2005, said Talcott, who is in a joint research and teaching position with the department of nutrition and food science and the department of veterinary physiology and pharmacology.

"Over $7 billion was spent on herbal dietary supplements in 2005." These supplements are plant-based, including grape seed extract, St. John's wort, ginseng and biloba extract, she added.

"In addition to that there is the segment of so-called 'functional foods,' including antioxidant foods - for example, fruit juices and beverages and grain-based products," Talcott said.

The amount spent on these foods each year "has increased drastically; however, we do not know yet how efficacious these different antioxidants really are in the prevention of chronic diseases such as cardiovascular disease and cancer," she said. "We also do not know very much about the mechanisms, which appear to include antioxidant and anti-inflammatory effects of these phytochemicals."

This can be important to health since these reactive oxygen species or 'free radicals' may play a role in some diseases, including Alzheimer's, cancer and atherosclerosis, she said.

"However, other mechanisms, including the prevention of chronic inflammation and interaction with intracellular mechanisms, may be as important in the prevention of chronic diseases," she said. But are they safe? Are they efficient? How much is required? And how much is too much? Talcott is looking for the answers to these questions through her research.

"My overall goal is to find out more about the safety and efficacy of phytochemical dietary supplements," she said. Because these items are already popular with consumers, "we need to follow up with research. We know very little about (dose) recommendations and how safe (they are)."

Phytochemicals, also called secondary plant compounds - including antioxidants - have been defined as chemicals found in plants that have protective or disease-fighting properties ( http://phytochemicals.info/ ).

Pomegranate juice and extract have been the focus of much of her studies. Because these are used in different food products, they are found as ingredients in many different items in supermarkets, Talcott said.

She has also done research on the properties of muscadine grapes and acai, a palm fruit from Brazil, as well as isolated compounds including quercetin and ellagic acid, which are also sold as dietary supplements.

The results of some of her studies were published in the Oct. 13, 2006, edition of the Journal of Agricultural and Food Chemistry. The article was titled "Absorption, Metabolism and Antioxidant Effects of Pomegranate (Punica granatum L.) Polyphenols after Ingestion of a Standardized Extract in Healthy Human Volunteers."

In addition to her research, Talcott teaches a class on "Special Topics in Phytochemicals of Fruits and Vegetables" for students who are majoring in nutrition and food science. Many of the students are planning to enter medical or pharmacy school, she added.

"It is my goal to give students as much relevant information, which they directly can apply in their desired profession," Talcott said. "Consumers and patients have many questions about herbal dietary supplements, and health care professionals and (members of the) food industry are and will be even more confronted with these questions."

For example, Dr. Joseph M. Betz was a recent guest lecturer in Talcott's class. Betz is the director of the Dietary Supplement Methods and Reference Materials Program Office of Dietary Supplements at the National Institutes of Health in Bethesda, Md. He discussed Food and Drug Administration rules as to the differences between foods and drugs and how each must be labeled. With regard to herbal supplements, this can sometimes be a little tricky, he said.

During the question and answer period at the end of his talk, one of the students asked about a recent study on antioxidants. According to news reports, the study seemed to find that antioxidants - especially vitamins A and E - don't have the beneficial properties they are thought to have and may even increase mortality.

Talcott offered this clarification in regard to the study: "This study statistically analyzed many different clinical studies with vitamins A, E (and) C, beta-carotene and selenium. The performed statistical analysis indicated that vitamin A and E and beta-caraotene may increase mortality in some of the selected studies. The meaning of this study currently is being discussed."

The study looked at synthetic antioxidants, she said, which are not the same compounds that she is researching.

"Even though we still have a lot to learn about the efficacy, safety and dosing recommendations for herbal supplements and antioxidant foods, we can be confident to recommend a healthy balanced diet according to the food-pyramid rich in fresh fruits and vegetables. I also would not see a problem with the intake of reasonable amounts of standardized high-quality antioxidant dietary supplements," she said.

"It is my long-term goal to see science-based intake recommendations developed for those herbal plant compounds which have a proven potential in the promotion of health and prevention of chronic disease."

Texas A&M University
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The negative effect of antioxidant supplements

Use of some antioxidant supplements may increase mortality risk

Contradicting claims of disease prevention, an analysis of previous studies indicates that the antioxidant supplements beta carotene, vitamin A, and vitamin E may increase the risk of death, according to a meta-analysis and review article in the February 28 issue of JAMA.

Many people take antioxidant supplements, believing they improve their health and prevent diseases. Whether these supplements are beneficial or harmful is uncertain, according to background information in the article.

Goran Bjelakovic, M.D., Dr.Med.Sci., of the Center for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues conducted an analysis of previous studies to examine the effects of antioxidant supplements (beta carotene, vitamins A and E, vitamin C [ascorbic acid], and selenium) on all-cause death of adults included in primary and secondary prevention trials. Using electronic databases and bibliographies, the researchers identified and included 68 randomized trials with 232,606 participants in the review and meta-analysis. The authors also classified the trials according to the risk of bias based on the quality of the methods used in the study, and stratified trials as "low-bias risk" (high quality) or "high-bias risk" (low quality).

In an analysis that pooled all low-bias risk and high bias risk trials, there was no significant association between antioxidant use and mortality. In 47 low-bias trials involving 180,938 participants, the antioxidant supplements were associated with a 5 percent increased risk of mortality. Among low-bias trials, use of beta carotene, vitamin A, and vitamin E was associated with 7 percent, 16 percent and 4 percent, respectively, increased risk of mortality, whereas there was no increased mortality risk associated with vitamin C or selenium use.

"Our systematic review contains a number of findings. Beta carotene, vitamin A, and vitamin E given singly or combined with other antioxidant supplements significantly increase mortality. There is no evidence that vitamin C may increase longevity. We lack evidence to refute a potential negative effect of vitamin C on survival. Selenium tended to reduce mortality, but we need more research on this question," the authors write.

"Our findings contradict the findings of observational studies, claiming that antioxidants improve health. Considering that 10 percent to 20 percent of the adult population (80-160 million people) in North America and Europe may consume the assessed supplements, the public health consequences may be substantial. We are exposed to intense marketing with a contrary statement, which is also reflected by the high number of publications per included randomized trial found in the present review."

"There are several possible explanations for the negative effect of antioxidant supplements on mortality. Although oxidative stress has a hypothesized role in the pathogenesis of many chronic diseases, it may be the consequence of pathological conditions. By eliminating free radicals from our organism, we interfere with some essential defensive mechanisms . Antioxidant supplements are synthetic and not subjected to the same rigorous toxicity studies as other pharmaceutical agents. Better understanding of mechanisms and actions of antioxidants in relation to a potential disease is needed," the researchers conclude.

JAMA and Archives Journals
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Beneficial effect of apples and fish

Eating apples and fish during pregnancy may protect against childhood asthma and allergies

Women who eat apples and fish during pregnancy may reduce the risk of their children developing asthma or allergic disease, suggests a new study presented at the American Thoracic Society 2007 International Conference, on Sunday, May 20.

The SEATON study, conducted at the University of Aberdeen, UK, found that the children of mothers who ate the most apples were less likely to ever have wheezed or have doctor-confirmed asthma at the age of 5 years, compared to children of mothers who had the lowest apple consumption. Children of mothers who ate fish once or more a week were less likely to have had eczema than children of mothers who never ate fish.

The study did not find any protective effect against asthma or allergic diseases from many other foods, including vegetables, fruit juice, citrus or kiwi fruit, whole grain products, fat from dairy products or margarine or other low-fat spreads.

The researchers studied 1212 children born to women who had filled out food questionnaires during their pregnancy. When the children were 5 years old, the mothers filled out a questionnaire about the children's respiratory symptoms and allergies, as well as a questionnaire about their child's food consumption.

The children were also given lung function and allergy tests. Previous studies in the same children have found evidence for protective effects of vitamin E and D and zinc during pregnancy in reducing the risk of children's wheeze and asthma, notes researcher Saskia Willers, M.Sc. of Utrecht University in the Netherlands. If the new results are confirmed, she says, "recommendations on dietary modification during pregnancy may help to prevent childhood asthma and allergy."

Willers concludes that at least until age 5, a mother's diet during pregnancy might be more influential on a child's respiratory health than the child's own diet. She notes that further study of this group of children will be needed to see whether the association with the mothers' diet declines in older children, and if mothers' and their childrens' diets interact in older children.

Willers suggests that the beneficial effect of apples may come from powerful antioxidants called flavonoids, while fish's protective effect may come from omega-3 fatty acids, which other studies have suggested have a protective effect on the heart and may have a protective effect in asthma. "Other studies have looked at individual nutrients' effect on asthma in pregnancy, but our study looked at specific foods during pregnancy and the subsequent development of childhood asthma and allergies, which is quite new," Willers says. "Foods contain mixtures of nutrients that may contribute more than the sum of their parts."

American Thoracic Society
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Fruit - high antioxidant properties

Native fruits bear sweet antioxidants

Twelve native Australian fruits that are exceptional sources of antioxidants have been identified in research published in the journal Innovative Food Science & Emerging Technologies.

The fruits: Kakadu plum, Illawarra plum, Burdekin plum, Davidson's plum, riberry, red and yellow finger limes, Tasmanian pepper, brush cherry, Cedar Bay cherry, muntries and Molucca raspberry; were compared with blueberries (cultivar Biloxi) - a fruit renowned for its high antioxidant properties.

"Finding unique food ingredients and flavours with health-promoting properties is a key market requirement these days," says research team leader, Food Science Australia's Izabela Konczak. "And, by encouraging growers to cultivate native fruits, we are also contributing to the growing need to ensure agriculture becomes more sustainable."

Co-author Dr Michael Netzel - a post-doctoral researcher at Food Science Australia supported by Germany's Alexander von Humboldt Foundation - says the native fruits were shown to be rich sources of antioxidants, with stronger radical scavenging activities than blueberries.

"Compared to blueberries' TEAC value of 39.45 trolox equivalents per gram, Kakadu plum and Burdekin plum had TEAC values of 204.8 and 192.0 trolox equivalents per gram," Dr Netzel says.

"Using native Australian fruits as a source of phytochemicals for use in foods could offer enormous opportunities for the food and functional food industries.

"Studies to identify additional antioxidant compounds as well as clinical trials for testing the fruits' bioactivity in vivo, are in progress." he says.

While Australian native fruits have been eaten by indigenous people for thousands of years, this is the first scientific study of the fruits as a source of antioxidants and confirms preliminary results published in the Journal of Agricultural and Food Chemistry in 2006.

This research supports CSIRO efforts to realise the potential of Australia's fledgling native food industry which is currently estimated to be worth $A14 million annually.

Food Science Australia is a joint venture between CSIRO and the Victorian Government.

CSIRO Australia
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Antioxidants and retinal degeneration

Antioxidants may slow vision loss

Scientists at Johns Hopkins have successfully blocked the advance of retinal degeneration in mice with a form of retinitis pigmentosa (RP) by treating them with vitamin E, alpha-lipoic acid and other antioxidant chemicals.

"Much more work needs to be done to determine if what we did in mice will work in humans," said Peter Campochiaro, the Eccles Professor of Ophthalmology and Neuroscience at The Johns Hopkins University School of Medicine. "But these findings have helped to solve a mystery."

In patients with RP, rod photoreceptors die from a mutation, but it has not been known why cone photoreceptors die. After rods die, the level of oxygen in the retina goes up, and this work shows that it is the high oxygen that gradually kills the cones. Oxygen damage is also called "oxidative damage" and can be reduced by antioxidants. So for the first time, scientists have a treatment target in patients with RP, added Campochiaro. His team's findings appeared in the July online edition of the Proceedings of the National Academy of Sciences.

Retinas in all mammals, from mouse to man, are made up of light-sensitive cells known as cones and rods, named for their shapes, which convert light into nerve signals that are then transmitted to the brain via the optic nerve. Cones are needed to see colors and make vision possible in bright light, whereas the far more numerous rods permit sight in low light. The human retina contains approximately 125 million rod cells and six million cone cells. In diseases like RP and age-related macular degeneration (AMD), these cells die off and eventually lead to blindness (in the case of RP) or legal blindness (in the case of AMD).

In earlier studies exposing mice to pure oxygen, the Hopkins scientists found that high levels of oxygen in the retina killed both rods and cones, said Campochiaro. "This was the clue that the high oxygen levels that occur naturally in the retina after rods die was the suspect regarding cone cell death. To test this, we used antioxidants, which protect cells from oxygen damage, and since they allowed many more cones to survive, it proves that the suspect is guilty."

In this mouse model of retinal degeneration, the rods have completely degenerated by the 18th day of age, and then the cones start to degenerate, with 85 percent of them dying off by the time the mice are 35 days old. Campochiaro and his team injected vitamin E, vitamin C, alpha-lipoic acid or an antioxidant similar to superoxide dismutase between the 18th and 35th day. In mice that received vitamin E or alpha-lipoic acid, 40 percent of the cones survived, about twice as many as in the control group or the groups treated with the other antioxidants, which had no identifiable effect.

"What's clear is the link between oxygen and photoreceptor damage, as well as the potential of antioxidant treatment," Campochiaro said. "These experiments suggest that an optimized regimen of antioxidants may help to protect patients with retinitis pigmentosa."

Campochiaro emphasized that even if found valuable, antioxidant treatment of RP, a group of inherited blinding diseases with complex genetic roots, would not cure the disease. But the salvaging of cones, which are concentrated in the retina's macula and are critical to central vision, could serve as a "maintenance therapy," he said. "That alone would be an enormous help."

RP affects only about 100,000 people in the United States. But the oxygen damage has also been implicated in other more pervasive eye diseases, like AMD and cataracts.

Antioxidants naturally occur in some fruits and vegetables, and are available as supplements, but Campochiaro said it remains unclear whether the amounts of antioxidants consumed in foods provided any benefit to people with these types of vision impairments.

Johns Hopkins Medical Institutions
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