1/23/2009

Ingredient used in dandruff shampoos a potential treatment for seizures

Researchers at Johns Hopkins have discovered that the same ingredient used in dandruff shampoos to fight the burning, itching and flaking on your head also can calm overexcited nerve cells inside your head, making it a potential treatment for seizures. Results of the study can be found online in Nat...

Researchers at Johns Hopkins have discovered that the same ingredient used in dandruff shampoos to fight the burning, itching and flaking on your head also can calm overexcited nerve cells inside your head, making it a potential treatment for seizures. Results of the study can be found online in Nature Chemical Biology.



Epilepsy and other seizure disorders result when nerves excessively or inappropriately %26#8220;fire%26#8221; in the brain. The brain%26#8217;s %26#8220;off%26#8221; switches fail in part due to protein defects that prevent potassium from exiting nerve cells and calming them. %26#8220;Channels that carry potassium,%26#8221; says Min Li, Ph.D., professor of neuroscience at Johns Hopkins, %26#8220;must open on cue to make sure nerve cells only fire for defined periods of time.%26#8221;


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In their studies of these channels, Li and his colleagues developed a new way of testing thousands of druglike molecules to find any that could turn the potassium switch on or off. Their approach involved chemically shaving off all the potassium channels on the cell surface and forcing the cells to make new channels. By measuring the activity of the new channels, the researchers could identify molecules that accelerated the recovery.



One chemical that proved quite effective in improving channel recovery was zinc pyrithione (ZnPy), the active ingredient in many dandruff shampoos. Li explains that ZnPy has a shape that allows it to fit into the gate region of the channel protein and allow more potassium flow. %26#8220;If you think of these channels as doors on the cell%26#8217;s surface,%26#8221; Li says, %26#8220;then ZnPy made this door both easier to open and stay open longer. It%26#8217;s like a tunable hinge that helps sticky doors swing freely.%26#8221;



The researchers then tested defective channels that contain the same mutations known in humans to cause mild epilepsy-like seizures in infants. Bathing cells with small amounts of ZnPy caused the mutant potassium channels to let three times as much potassium flow through, raising the possibility of restoring normal nerve cell activity.



%26#8220;Most drug discoveries uncover chemicals that stop things from working - it%26#8217;s a lot easier to close or block a door than open it,%26#8221; Li says. %26#8220;But here we found a chemical that makes a defective protein work better. So now we have a chance to actually try to fix the causes of epilepsy, rather than traditionally circumventing them. Plus, this study really shows that we don%26#8217;t fully appreciate the biological roles of many familiar chemicals that surround us.%26#8221;



Source: Johns Hopkins Medical Institutions


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Depression may be an early symptom of Parkinson's disease

Depression may be an early symptom of Parkinson's disease, according to research that will be presented at the American Academy of Neurology's 59th Annual Meeting in Boston, April 28May 5, 2007.The study looked at whether people who are taking antidepressant medications are more likely to develop Pa...

Depression may be an early symptom of Parkinson's disease, according to research that will be presented at the American Academy of Neurology's 59th Annual Meeting in Boston, April 28 %26#8211; May 5, 2007.



The study looked at whether people who are taking antidepressant medications are more likely to develop Parkinson's disease than people who are not taking the medications. It found that, in the year before their Parkinson's disease was diagnosed, people who were taking antidepressants were nearly twice as likely to develop Parkinson's disease as those who were not taking antidepressants.


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"This should not be interpreted as evidence that antidepressants cause Parkinson's disease," said Miguel Hernan, MD, DrPH, of Harvard School of Public Health in Boston. "The relationship is only apparent in the year before the onset of the disease, which suggests that depression is an early symptom of the disease."



For the study, researchers examined a database of more than three million people in the United Kingdom and identified 1,052 people with Parkinson's disease and matched them with 6,634 people without the disease. Then they looked at antidepressant use before the onset of Parkinson's disease.



The increased risk of developing Parkinson's in the year before diagnosis was true for both men and women, across age groups, and for those who used both types of antidepressants, tricyclic antidepressants and SSRIs, or selective serotonin reuptake inhibitors.



Source: American Academy of Neurology


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How plants make vitamin C

Vitamin C is possibly the most important small molecule whose biosynthetic pathway remained a mystery. That is until now.A group of UCLA and Dartmouth researchers, who normally work on genes involved in aging and cancer in animals, discovered the last piece of the puzzle, they report in a study publ...

Vitamin C is possibly the most important small molecule whose biosynthetic pathway remained a mystery. That is until now.



A group of UCLA and Dartmouth researchers, who normally work on genes involved in aging and cancer in animals, discovered the last piece of the puzzle, they report in a study published online April 26 in the Journal of Biological Chemistry.



Dr. Steven Clarke of the UCLA Molecular Biology Institute and the Department of Chemistry and Biochemistry explains, "We were working on an interesting gene in worms." One insight led to another until, "We uncovered the last unknown enzyme in the synthesis of vitamin C in plants," said Dr. Charles Brenner of Dartmouth Medical School's Norris Cotton Cancer Center and Department of Genetics.


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An essential vitamin for people, vitamin C is well known as an antioxidant and enzyme cofactor. Humans lost the ability to make vitamin C and need to take it up from dietary sources, particularly from plants.



Only in 1998 was a biosynthetic pathway proposed to explain how plants make vitamin C. Research since then has confirmed much of the pathway, although the gene responsible for the seventh step of the proposed 10-step pathway from glucose to vitamin C remained unknown.



The work began in an effort to understand the role of a gene in C. elegans, a tiny worm used as a model for aging studies by researcher Tara Gomez in Clarke's UCLA laboratory. The sequence of the gene suggested that it is related to a family of genes altered in cancer, termed HIT genes, that Brenner studies at Dartmouth.



Collaboration between the two laboratories revealed similarity of the worm gene to the product of the VTC2 gene of Arabidopis thaliana, a small roadside plant whose genetics have been well studied. Mutations in this plant gene had been previously linked to low levels of vitamin C. So the hunt was on to determine how its product would contribute to vitamin C synthesis.



The researchers, led by Brenner and Clarke, reconstituted in test tubes the long mysterious seventh step in vitamin C synthesis, a reaction they describe as the first committed step. They liken the first six steps in vitamin C synthesis to a roadmap with multiple possible routes from glucose to a variety of cellular compounds. Once the product of the sixth step, a compound called GDP-L-galactose, can take the exit marked VTC2, however, the atoms are reconfigured toward making vitamin C, specifically, and little else. The remaining three steps, like a curving driveway, require some turns but no real choices and no backing-up.



Through efforts led by UCLA postdoctoral fellow Dr. Carole Linster, the plant VTC2 enzyme was expressed and purified from bacteria. After preparing their own GDP-L-galactose, the team showed that VTC2 is responsible for the long sought seventh step in vitamin C synthesis.



Since enzymes catalyzing the first committed steps of a pathway represent sites of biological regulation, the researchers hope their discovery may lead to new strategies for increasing vitamin C levels in food crops, which could mean more nutritious foods as well as potentially higher crop yields. They still need to find out what VTC2-related genes do in animals and how these genes may relate to aging and cancer.



Source: Dartmouth Medical School


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Tart cherries may be good for health

Tart cherries may be good for more than just making pie, according to new data from an animal study conducted by University of Michigan Health System researchers and presented today at a major scientific meeting.In a study involving rats, the researchers report that animals that received powdered ta...

Tart cherries may be good for more than just making pie, according to new data from an animal study conducted by University of Michigan Health System researchers and presented today at a major scientific meeting.



In a study involving rats, the researchers report that animals that received powdered tart cherries in their diet had lower total cholesterol, lower blood sugar, less fat storage in the liver, lower oxidative stress and increased production of a molecule that helps the body handle fat and sugar, compared with rats that didn't receive cherries as part of an otherwise similar diet. All of the rats had a predisposition toward high cholesterol and pre-diabetes, but not obesity.


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All the measures on which the two groups of animals differed are linked to metabolic syndrome, a collection of risk factors linked to high rates of heart disease and Type 2 diabetes. Tens of millions of Americans have metabolic syndrome; most don't know it.



The researchers say the correlation between cherry intake and significant changes in metabolic measurements suggest a positive effect from the high concentrations of antioxidant compounds called anthocyanins that are found in tart cherries. The new results were given today in an oral presentation at the Experimental Biology 2007 meeting in Washington, D.C.



It's not yet known if cherry-rich diets might have a similar impact in humans, but a U-M team will soon launch a small clinical trial to start to find out. Meanwhile, additional research is being carried out in animals prone to both obesity and diabetes.



The study's lead author is E. Mitchell Seymour, M.S., a U-M research associate and supervisor of the U-M Cardioprotection Research Laboratory, which studies the potential preventive benefits of antioxidant-rich foods. Support for the new study comes from an unrestricted grant from the Cherry Marketing Institute, a trade association for the cherry industry. CMI has no influence on the design, conduct or analysis of any U-M research it funds.



Seymour and the laboratory's director, U-M cardiac surgeon Steven Bolling, M.D., caution that their results cannot be directly translated into humans. But they are encouraged by the positive signs seen in the new data.



"Rats fed tart cherries as 1 percent of their total diet had reduced markers of metabolic syndrome," says Seymour. "Previous research by other groups studied pure anthocyanin compounds rather than anthocyanin-containing whole foods, and they used concentrations of anthocyanins that would be very difficult if not impossible to obtain in the diet."



He continues, "We are interested in a whole-foods approach, using amounts of fruit that are relevant to human diets. We are enthusiastic about the findings that tart cherries conferred these beneficial effects at such a modest daily intake."



The potential for protective effects from antioxidant-rich foods and food extracts is a promising area of research, says Bolling, who is the Gayle Halperin Kahn Professor of Integrative Medicine, a professor of cardiac surgery, co-director of U-M Integrative Medicine and member of the U-M Cardiovascular Center.



"These data from whole tart cherries join other findings that suggest a correlation between anthocyanin intake and reductions in cardiovascular and metabolic risk factors," he says. "But there is still a long way to go before we can advocate any course of action for humans. Still, the growing body of knowledge is encouraging."



Bolling and Seymour performed the study using 48 male Dahl Salt-Sensitive rats, which are bred for their susceptibility to salt-linked high blood pressure, high cholesterol and impaired glucose tolerance.



For 90 days beginning in their sixth week of life, the rats were fed either a carbohydrate-enriched diet or a diet that, by weight, included 1 percent cherries or 10 percent cherries. The higher cherry dose was used to look for any toxic effects; none were seen.



The cherries were Montmorency tart cherries grown in northern Michigan, frozen, and powdered. Michigan is the nation's largest producer of tart cherries, which are used in pies and jams as well as juice. They are different from the sweet Bing cherries that are often eaten raw, and have higher concentrations of antioxidant anthocyanins than sweet cherries.



By the end of the study, the rats that received the 1-percent cherry diet had total cholesterol, triglyceride, glucose and insulin levels that were significantly lower than those of the rats that did not receive cherries. The same was true for those on the 10-percent cherry diet, compared with rats that received a diet with an equivalently high level of carbohydrates not from cherries.



The researchers also measured plasma TEAC, a measure of antioxidant capacity in the blood on which a higher reading means better ability to neutralize damaging free radical molecules produced in the body during metabolism. The rats that received cherries had higher antioxidant capacity, indicating lower oxidative stress in their bodies, than those that did not.



In addition to blood measures, the researchers measured the level of fat in the livers of the rats, and the genetic expression of PPAR (peroxisome proliferator-activating receptor) in the liver.



The "fatty liver" measure is important because the storage of excess energy as fat in the liver is a common effect in metabolic syndrome %26#8211; and because it feeds the vicious cycle of increased cholesterol and decreased response to insulin that can lead to cardiovascular disease and Type 2 diabetes.



Meanwhile, the measure of PPAR messenger RNA in the liver reflects the readiness of the liver tissue to express functional PPAR. PPAR is important to the process by which the body burns fat instead of storing it, and it is important in the formation of blood lipids like LDL, typically known as the "bad cholesterol". Drugs in the classes known as thiazolidinediones and glitazars activate PPAR and are often used to manage high cholesterol and risk for Type 2 diabetes.



In the current study, the rats that received cherries had both a lower level of fat in their livers, and a higher expression of the PPAR gene, than those that did not %26#8211; and the correlation between the two was dose-dependent.



Now, the Cardioprotection Laboratory team has embarked on a new study in rats that have Type 2 diabetes, both with and without obesity and in the presence of low-fat and high-fat diets. They will look at whether tart cherries have an impact on the storage of fat in fat tissue and in muscle, and on the production of specific blood lipids like LDL and HDL. In addition, they will characterize cherries chemically, to assess the levels of phytochemicals in whole cherries, cherry juice and dry cherries.



Meanwhile, U-M Integrative Medicine co-director Sara Warber. M.D., an assistant professor of family medicine at the U-M Medical School, will lead a pilot clinical trial of whole tart cherries in humans. The study will enroll healthy individuals who will spend a night at the U-M General Clinical Research Center, and have their blood tested multiple times to look for the breakdown products of cherries.



Source: University of Michigan


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Zorro-LNA has potential to stop genetic disorders in their tracks

A study to appear in the June 2007 issue of The FASEB Journal describes a new agent, called "Zorro-LNA," which has the potential to stop genetic disorders in their tracks. In the study, researchers from the Karolinska Institute in Stockholm, Sweden, describe how they developed Zorro-LNA to bind with...

A study to appear in the June 2007 issue of The FASEB Journal describes a new agent, called "Zorro-LNA," which has the potential to stop genetic disorders in their tracks. In the study, researchers from the Karolinska Institute in Stockholm, Sweden, describe how they developed Zorro-LNA to bind with both strands of a gene%26#8217;s DNA simultaneously, effectively disabling that gene. This development has clinical implications for virtually every human condition caused by or worsened by dominant defective genes. Examples include: Huntington%26#8217;s disease, familial high cholesterol, polycystic kidney disease, some instances of glaucoma and colorectal cancer, and neurofibromatosis, among others.


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"Zorro-LNA is a new substance that targets DNA and turns off genes," said co-author Edvard Smith of the Karolinska Institute in Sweden. "It has the potential of becoming a new drug for the treatment of human genetic disease."



The findings described in this article significantly raise the possibility that new therapies could arise where defective DNA is deactivated more completely and more thoroughly than ever before. For instance, Zorro-LNA could be used in combination with "RNA interference" (RNAi). Like Zorro-LNA, RNAi has the ability to deactivate genes, but does so by degrading the gene%26#8217;s RNA. In addition, Zorro-LNA could be used to deactivate certain genes in stem cells, which could eventually lead to the development of new cells, tissues, or organs. The discovery of RNAi was recognized by a Nobel Prize award in 2006 to two American scientists.



"This is a major development in the treatment not only of genetic diseases, but also of acquired diseases when microbes or toxins cause genes to go awry" said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "One might say these researchers have found a gene-hunter%26#8217;s Holy Grail for which scientists have been hunting for many years. Zorro-LNA should give us a new, safe way of blocking the effects of errors in our genetic repertoire."



Source: Federation of American Societies for Experimental Biology


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Eating pistachios may reduce body's response to stress

Eating pistachios may reduce your body's response to the stresses of everyday life, according to a Penn State study."A ten-year follow-up study of young men showed that those who had larger cardiovascular responses to stress in the lab, were more likely to contract hypertension later in life," says ...

Eating pistachios may reduce your body's response to the stresses of everyday life, according to a Penn State study.



"A ten-year follow-up study of young men showed that those who had larger cardiovascular responses to stress in the lab, were more likely to contract hypertension later in life," says Dr. Sheila G. West, associate professor of biobehavioral health. "Elevated reactions to stressors are partly genetic, but can be changed by diet and exercise. Lifestyle changes can make the biological reactions to stress smaller."


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West and her colleagues investigated the effects of pistachios on standardized stressors on subjects who had high cholesterol, but normal blood pressure. They used a randomized, crossover controlled feeding study design and all three diets all contained the same number of calories. After a two-week run-in diet containing 35 percent fat and 11 percent saturated fats, each test diet lasted for four weeks during which time participants ate only foods supplied by the study. The researchers reported the results of this study at Experimental Biology 2007 today (April 30) in Washington, D.C.



The diets included a Step I Diet %26#8211; a standard heart healthy diet with 25 percent fat and 8 percent saturated fat, a diet containing 1.5 ounces of pistachios that was a Step I Diet with 30 percent total fat and 8 percent saturated fat and a diet containing 3 ounces of pistachios that was a Step I Diet containing 34 percent fat and 8 percent saturated fat. At the end of each four-week diet regime, the researchers measured blood pressure and total peripheral vascular resistance at rest and during two stress tests.



The two tests consisted of a physical test and a psychological test. The physical test consists of putting one foot in a bucket of ice water for 2.5 minutes. The psychological test asks participants to listen to two numbers, add them in their head and say the answer. Then they hear another number and they must add it to the second number they heard, not the sum they spoke.



"The ice water is a stimulus for the sympathetic nervous system, but it is very different form the stressors we encounter every day," says West. "We also wanted to see if the reaction occurred when the stress was nonphysical, so we used the math test."



The researchers found that both pistachio containing diets reduced the stress effects on blood pressure, but that the 1.5 ounce pistachio diet reduced systolic blood pressure by 4.8 millimeters of mercury while the 3-ounce pistachio diet only reduced systolic blood pressure by 2.4 millimeters of mercury. The diets had no effect on normal, resting blood pressure.



"When we only look at blood pressure, these results are confusing," says West. "If it is the pistachios, why is it not dose related?"



When the researchers looked at total peripheral vascular resistance, it was clear that the 3-ounce diet caused greater relaxation of arteries. Because the body tightly regulates blood pressure, rather than allowing blood pressure to drop further, the heart compensated by pumping more forcefully.



"The relaxation of blood vessels after the 3-ounce pistachio diet likely reduced the workload on the heart," says West. "This pattern of change would be beneficial if it is maintained long term. It is possible that other foods that are high in unsaturated fat and antioxidants would have a similar effect."



Source: Penn State


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Statins help memory in Alzheimer's

Treatment with Simvastatin, one of the statin drugs widely used for lowering cholesterol in humans, significantly improved spatial memory - how to navigate a water maze - in mice genetically bred to have an Alzheimers like disease. Although statin improved memory in both males and females, the resul...

Treatment with Simvastatin, one of the statin drugs widely used for lowering cholesterol in humans, significantly improved spatial memory - how to navigate a water maze - in mice genetically bred to have an Alzheimer%26#8217;s like disease. Although statin improved memory in both males and females, the results were more pronounced in males.



Dr. H. A. Morcos, chair of Pharmacology at the American University of Antigua, and colleagues at Florida A %26amp; M University presented the study April 30 at Experimental Biology 2007 in Washington, DC. His presentation is part of the scientific program of the American Society for Pharmacology and Experimental Therapeutics.


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The study confirmed the Morcos laboratory%26#8217;s earlier findings of improved memory in this mouse model of Alzheimer%26#8217;s and discovered new information about the neurochemical basis of the beneficial effects. Various studies have found evidence of a strong relationship between memory deficits and high levels of cholesterol in the brain, suggesting that statin%26#8217;s effects on memory might be due to a reduction in cholesterol biosynthesis.



In this study, Dr. Morcos found that nNOS (neuronal nitric oxide synthase) levels were significantly higher in the hippocampus and cortex of statin treated groups as compared to similar mice that did not receive statin. Furthermore, the levels of nNOS proteins were statistically higher in the hippocampus of the statin treated animals than in the cortex. nNOS is responsible for the release of nitric oxide, a substance that causes dilation of the blood vessels in the brain, which eventually will increase blood flow and improve circulation to the memory region of the brain. These findings suggest that increases in brain nNos levels may play an important role in statin-induced improvement of spatial reference memory.



The transgenic mice used in the study are homozygous for the gene for beta amyloid protein, making it inevitable that they develop an Alzheimer%26#8217;s like disease as they age. In fact, they lose their memory by nine months of age. These animals, together with regular mice without the beta amyloid genes, were acclimated for one week, with as much food and water as they wished, then divided into four groups. Half the %26#8220;Alzheimer%26#8217;s mice%26#8221; and half the normal mice received 10 mg/kg Simvastatin for seven days, while half of each group only received saline. Each day the mice had two swimming trials in the water maze, giving them a chance to learn how to reach a platform. Food was always available and safety makes taken during the entire trial.



On the seventh day the animals were tested for spatial memory, in other words low long it took them to find the platform. The Alzheimer%26#8217;s mice that received statin were able to find the platform while none of the transgenic mice receiving only saline were able to do so. Normal mice on statin also showed improvement in the time they usually take to reach the platform compared to normal mice on saline. After the maze test, brain tissue then was studied to determine levels of nNOS.



Source: Federation of American Societies for Experimental Biology


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Pistachios may lower cholesterol and provide the antioxidants

A handful of pistachios may lower cholesterol and provide the antioxidants usually found in leafy green vegetables and brightly colored fruit, according to a team of researchers."Pistachio amounts of 1.5 ounces and 3 ouncesone to two handfulsreduced risk for cardiovascular disease by significantly r...

A handful of pistachios may lower cholesterol and provide the antioxidants usually found in leafy green vegetables and brightly colored fruit, according to a team of researchers.



"Pistachio amounts of 1.5 ounces and 3 ounces %26#8211; one to two handfuls %26#8211; reduced risk for cardiovascular disease by significantly reducing LDL cholesterol levels and the higher dose significantly reduced lipoprotein ratios," says Sarah K. Gebauer, graduate student in integrative biosciences, Penn State, to attendees at the Experimental Biology meeting today (April 30) in Washington, D.C.


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The researchers conducted a randomized, crossover design, controlled feeding experiment to test the effects of pistachios added to a heart healthy moderate-fat diet on cardiovascular disease risk factors. Controlled feeding experiments provide all the food eaten by study subjects for the duration of the study segment.



Participants began the study by eating an Average American Diet consisting of 35 percent total fat and 11 percent saturated fat for two weeks. They then tested three diets for four weeks each with a two-week break between each diet.



All three diets were variations on the Step I Diet, a cholesterol-lowering diet in general use. The diets included a Step I Diet without pistachios which had 25 percent total fat and 8 percent saturated fat; a Step I Diet including 1.5 ounces of pistachios per day which had 30 percent total fat and 8 percent saturated fat, and a Step I Diet including three ounces of pistachios per day which had 34 percent total fat and 8 percent saturated fat. The researchers added pistachios into the diets by including about half the amount of pistachios as a snack and by incorporating the rest into such foods as pistachio muffins, granola and pistachio pesto.



"We had really good compliance and participants were generally pleased with the diets," says Gebauer.



Standard blood tests determined the various cholesterol levels in the participant%26#8217;s blood after each diet. Researchers found that 3 ounces of pistachios reduced the amounts of total cholesterol in the blood by 8.4 percent and low-density lipoprotein (LDL), the so-called bad cholesterol, by 11.6 percent. The study also found that non-high density lipoproteins (non-HDL) decreased by 11.2 percent. Non-HDL levels are considered reliable predictors of cardiovascular disease risk.



The three-ounce pistachio diet also decreased the ratios of total cholesterol to HDL, LDL to HDL and non-HDL to HDL and apolipoprotein B, which are all measures of cardiovascular disease risk. "We were pleased to see a difference between the two doses of pistachios for the lipoprotein ratios because it would appear that pistachios are causing the effect and that they act in a dose dependent way," says Gebauer.



In addition, during this study researchers, researchers looked at the effects of these diets on oxidized LDL and on antioxidants in the blood.



"We were trying to see if the increased levels of antioxidants provided by pistachios could reduce inflammation and oxidation," says Gebauer. Pistachios contain more lutein, %26#8211; normally found in dark leafy vegetables -- beta carotene %26#8211; a precursor to vitamin A %26#8211; and gamma tocopherol %26#8211; the major form of vitamin E %26#8211; than other nuts. It is oxidized LDL and other lipproteins that contribute to plaque formation in arteries.



The researchers reported that both the 1.5 and 3 ounce pistachio diets reduced oxidized LDL compared with the baseline diet. Pistachio-enriched diets also resulted in significantly higher levels of lutein in the blood. The increased lutein from the 3-ounce pistachio diet correlated with a reduction in oxidized LDL which may indicate that the lutein in pistachio nuts improves the risk of cardiovascular disease by reducing serum oxidized LDL.



"Our study has shown that pistachios, eaten with a heart healthy diet, may decrease a person's CVD risk profile," says Dr. Penny Kris-Etherton, distinguished professor of nutrition and primary investigator of the study.



Source: Penn State


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