|June 2003 |
Stress really is aging
A longitudinal study published online in the Proceedings of the National Academy of Sciences established a link between long term stress and the release of the proinflammatory cytokine interleukin-6. Interleukin-6 is involved in immune system regulation and is known to be a promoter of C-reactive protein, which is a risk factor in the development cardiovascular disease and myocardial infarction, adult-onset diabetes, osteoporosis, arthritis and congestive heart failure-all age-related diseases.
Researchers from Ohio State University studied a population of 119 men and women in the stressful situation of being the caregiver of a spouse with dementia and compared them to 106 noncaregivers. Participants, whose average age was 70.5, were evaluated by various standard assessments concerning perceived stress levels, depression and loneliness. Blood samples were taken periodically over a six year period to determine interleukin-6 levels.
Caregivers reported more stress and loneliness than noncaregivers. The researchers found that the caregivers had a rate of increase in interleukin-6 production four times that of noncaregivers over the period of the study. In former caregivers whose spouses died, interleukin-6 elevations did not differ from current caregivers for up to three years after the spouse's death, demonstrating a lasting effect of stress on immune function. The researchers found no differences in health problems or related behaviors to account for the difference in interleukin-6 production among the two groups.
These results illustrate a key mechanism by which stress may increase the risk of age-related diseases by prematurely aging the immune response. The authors suggest that other chronic stressors may also accelerate the age-related rise in interleukin-6 and increase the risk of diseases related to its elevation.
Antioxidants slow brain aging
An article published online in the Proceedings of the National Academy of Sciences reported that synthetic versions of the antioxidants superoxide dismutase and catalase may be more powerful than those that are made in the body in their ability to reverse the decline in memory that occurs with age. The NIA-funded study, conducted by researchers at the University of Southern California, Irvine, involved eight month old mice implanted with a pump that released one of the two synthetic compounds called EUK-189 and EUK-207 over a three month period. They found that mice treated with the compounds exhibited improved memory compared to the normal decline experienced in mice at this age. Additionally, the compounds significantly lowered lipid peroxidation and carbonyl oxidation (markers of oxidative stress) compared to levels found in control mice.
Oxidative stress has been implicated in the cognitive impairment seen in older animals and humans. Antioxidants such as superoxide dismutase and catalase combat oxidative stress by fighting the destructive chemicals that form in the body known as free radicals. However, these natural antioxidants and others such as vitamins C and E may not be as effective as those designed by science. Lead researcher and biological sciences professor in the USC College of Letters, Arts & Sciences, Michael Baudry, explained, "Because enzymes are huge molecules, they can't go through the cell membrane and they provoke an immune response. The body identifies them as foreign molecules and tries to destroy them. When the antioxidant Vitamin E, for example, interacts with a radical, it's a one-shot deal. It can't interact with another radical. Our molecules are small. They can get through the membranes and interact with more than one molecule of free radicals."
Predicting human trials as the next step in this work, Baudry added, "These drugs could eventually be adapted to fight almost any disease which has an oxidative component."
Smoke exposure depletes B vitamin, ups disease risk
In a study funded by the Centers for Disease Control and Prevention, research reported in the journal Nicotine & Tobacco Research has shown that exposure to cigarette smoke, whether active or passive, lowers blood levels of folate, an important member of the B vitamin complex that helps protect against birth defects, which has been found to be inversely associated in humans with heart disease and some cancers.
The study analyzed red blood cell and serum levels of folate and the nicotine byproduct cotinine in 15,564 adults seventeen years of age and older, who were questioned by the researchers on smoking and eating habits. It was found that both red blood cell levels of the vitamin, which reflect long term folate intake, and serum levels, which are a better indicator of recent consumption, declined with exposure to smoke. Subjects who were active smokers experienced a significantly greater loss of the vitamin than those exposed to second-hand smoke.
David M. Mannino, MD and colleagues at the Centers for Disease Control and Prevention stated, "Overall, we found that red blood cell folate levels in current smokers were 20 percent lower than those in our entire group of nonsmokers . . . The finding provides biological support for recent studies linking tobacco smoke exposure to heart disease and breast cancer and provides biological plausibility to examine the role of tobacco smoke exposure in other folate-related diseases such as neural tube defects and colon cancer."
Tea extract lowers cholesterol
A report published in the June 23 2003 issue of Archives of Internal Medicine provided the results of the first human study of its kind to reveal a cholesterol-lowering benefit for tea extracts.
Researchers in China enrolled 240 men and women with high cholesterol and randomly provided them with a placebo or a 375 milligram capsule containing 75 milligrams theaflavins from black tea, 150 milligrams catechins from green tea and 150 milligrams of tea polyphenols--the equivalent of thirty-five cups black tea and seven cups green tea. The participants received the capsules for twelve weeks, during which they continued to consume the low-fat diets they had adopted prior to the study.
Subjects who received the tea extract capsule were found to have lower cholesterol than the placebo group at the end of twelve weeks. Previous studies involving tea-drinking and consumption of green tea extract had not found a cholesterol-lowering effect associated with tea.
Lead author and associate professor of Medicine at Vanderbilt University Medical Center, Dr. David J. Maron, stated, ""Personally, I was very surprised. I expected, if anything, a very slight cholesterol-lowering effect. But what we saw was a 16 percent reduction in low density lipoprotein (LDL) cholesterol." He added, "The present study represents the first step in establishing the practicality, safety and LDL-lowering ability of this tea product. Although the results are exciting, we do not want people to take the extract in place of their medications. Unlike statins, this product has not been proven to prevent heart attacks or stroke, or to prolong life. The study shows that the tea extract is a useful adjunct to lowering LDL in people with high cholesterol already on a low-fat diet."
Dr Marron recommends further trials of the extract in combination with lipid-lowering medication, particularly statin drugs.
Soy isoflavones, miso, protect against breast cancer
The Journal of the National Cancer Institute published a report in its June 18 2003 issue that established a trend between increased consumption of soy isoflavones and the fermented soy paste miso, with a lower incidence of breast cancer among Japanese women. Isoflavones from soy include genistein and daidzein, which have been found to have a number of health benefits.
The researchers examined data obtained from the Japan Public Health Center-Based Prospective Study on Cancer and Cardiovascular Diseases, which enrolled 27,435 women and a similar number of men in January of 1990. Upon enrollment, participants completed a questionnaire concerning their intake of food and beverages, personal and family history of diseases, and other pertinent information. The subjects also provided information on their consumption of various types of soyfoods including miso soup. The participants were followed for ten years. During this period, 225 women were diagnosed with breast cancer. After disqualifying 5,583 women, the final analysis included 21,852 women of whom 179 had breast cancer diagnoses provided during follow-up.
Analysis of the data determined a significant inverse relationship between the risk of developing breast cancer and intake of isoflavones (as calculated from various soyfoods) and miso soup. Women whose isoflavone consumption was in the highest one-fourth of the participants had less than half the risk of breast cancer than women whose isoflavone consumption was in the lowest 25%. A stronger protective benefit for isoflavones emerged for postmenopausal women than for premenopausal women.
The fact that women in this study whose isoflavone consumption was the lowest still had an intake that is 250 times greater than that consumed daily by Caucasian women in the U.S. may account for the lower incidence of breast cancer found in Japanese women.
Licorice extract fights SARS
In a research letter published in the June 14 2003 issue of The Lancet, scientists from Germany's Frankfurt University discussed their finding that glycyrrhizin, the active component of licorice root, prevents the replication of the SARS associated virus. SARS, or severe acute respiratory syndrome, is a newly identified coronavirus that is highly infectious. Researchers are currently seeking the most effective ways to prevent and treat the disease.
The researchers assessed the antiviral properties of five different substances including glycyrrhizin on cell cultures infected with the SARS coronavirus. While a couple of the substances were minimally effective, the most potent inhibitor of the virus was glycyrrhizin. Glycyrrhizin also was found to inhibit adsorption and penetration of the virus early in its reproductive cycle. Four thousand milligrams per liter glycyrrhizin completely blocked replication of the virus in culture.
Possible mechanisms of action for glycyrrhizin include its ability to affect various cellular signaling pathways including protein kinase C, casein kinase II and the transcription factors activator protein 1 and nuclear factor KB. Glycyrrhizin also increases the production of nitrous oxide in macrophages, a substance that has been shown to inhibit the replication of several viruses. In its use in HIV and hepatitis C patients, side effects, such as elevated blood pressure, were infrequent and controllable. When high doses of glycyrrhizin were tried in clinical studies, few side effects were observed in comparison with other regimens.
Selenium may help protect high risk women from breast cancer
The June 15 2003 issue of Cancer Research reported that the trace mineral selenium may help prevent cancer in women whose genetic makeup puts them at higher risk of developing the disease. The University of Illinois researchers' finding was a result of comparing genes from 517 individuals without cancer to the genes of 79 breast cancer tissue samples. Lead researcher and University of Illinois professor Alan Diamond explained, "For over 20 years, animal studies have shown that tiny amounts of selenium in the diet can suppress cancer in several types of organs. The animal data is very strong, but human data is just emerging. We believe there are certain proteins in mammalian cells that contain selenium that can mediate the protective effects, but proving that is difficult. The way we studied this was to look at a certain selenium-containing gene that encodes for selenium-containing proteins, then examine their nucleotide -- or genetic code -- makeup for differences. We looked to see if there were differences in the frequency of versions of these genes both in tumor cells and from DNA from people who didn't have cancer."
Diamond and research assistant professor Ya Jun Hu focused on the selenium-containing antioxidant enzyme glutathione peroxidase. They found that cancer-free individuals had a difference in the frequency of versions of the genes for this protein compared to the frequency of genetic versions observed in breast cancer tissue. This led them to conclude that people with one version of the gene may need more selenium in order to obtain glutathione peroxidase's cancer-protective benefit.
Dr Diamond added, "Utimately, this might influence who would most benefit from having dietary supplementary selenium."
Aspirin use linked with lower leukemia incidence
The June 13 2003 issue of the American Association for Cancer Research journal, Cancer Epidemiology, Biomarkers & Prevention, published a report that links prevention of yet another cancer to regular aspirin use: adult leukemia. In previous studies, the use of aspirin has been found to be associated with a lower risk of breast, ovarian, colon, prostate, pancreatic and esophageal cancers.
Researchers from the Cancer Center at the University of Minnesota analyzed data obtained from the Iowa Women's Health Study, which surveyed 41,836 women ages 55 to 69 beginning in 1986. Participants answered questions concerning their medical history, diet, cancer risk factors and anthopometric data, including two questions concerning aspirin and nonsteroidal anti-inflammatory drug (NSAID) use. Women who did not complete the 1992 follow-up questionnaire, who had cancer before 1993 or did not answer the questions concerning aspirin and NSAID use were excluded from the current analysis, leaving 28,224 subjects. During the follow up period between 1993 and 2000, 81 of these participants developed leukemia. The researchers found that those who took aspirin at least twice a week had half the risk of developing leukemia than those who did not use aspirin. Nonaspirin NSAID use was not found to be protective against the disease.
Lead researcher and associate professor of pediatrics at the University of Minnesota, Julie Ross, PhD, summarized, "There's a growing body of evidence that aspirin may be a powerful cancer-preventing agent. To our knowledge, this is the first prospective study to examine the association between NSAID use and adult leukemia. A strength of our study was the ability to examine separately the effects of aspirin and non-aspirin NSAIDs. While the results are preliminary, notable differences in leukemia risk between aspirin and non-aspirin NSAID use definitely call for additional research with other large populations."
Alpha and beta carotene associated with lower heart disease risk in women
The June 2003 issue of the American Journal of Clinical Nutrition published findings from data obtained from the Nurses' Health Study that dietary intake of the antioxidant carotenoids alpha and beta carotene are inversely associated with coronary artery disease. The researchers, from the Children's Hospital Department of Medicine and Harvard University in Boston, utilized food-frequency questionnaires completed in 1984 by 73,286 female nurses which were updated in 1986, 1990 and 1994. The questionnaires were used to calculate intake of the carotenoids alpha-carotene, beta-carotene, lutein, zeaxanthin, lycopene and beta-cryptoxanthin.
Over the twelve year follow-up period 998 cases of coronary artery disease were identified among the study population. When the top one-fifth in consumption of each carotenoid were compared to those whose intake was in the lowest one-fifth of the population, alpha and beta carotene emerged as protective against coronary artery disease, while lutein/zeaxanthin, lycopene and beta-cryptoxanthin did not appear to have an association. Women whose consumption of beta-carotene was the highest had a 26 percent lower risk of developing coronary artery disease than women whose intake was the in the lowest group.
In explanation of a mechanism of action, the authors of this study wrote that carotenoids may prevent atherosclerosis by directly inhibiting low density lipoprotein oxidation, which has been demonstrated in vitro, or they may protect the cells of the vascular system from oxidative injury through actions independent of this effect. Because of the lack of cardiovascular benefit demonstrated in some clinical trials of beta-carotene supplements, the authors speculate that the benefits associated with higher dietary intake of this nutrient could be provided by alpha-carotene, which is found in carotenoid-rich foods.
New method to make coenzyme Q10 more affordable
Coenzyme Q10, one of the more important nutritional supplements, has heretofore been imported from Japan, and its relatively high cost passed on to consumers. Now professor of chemistry and biochemistry at the University of California, Santa Barbara, Bruce H. Lipshutz, has found a "short and sweet" way to manufacture this popular nutrient, and has patented the method.
Lipshutz's method uses economical transition metal catalysts such as cobalt and nickel complexes to synthesize the coenzyme, in contrast to the fermentation method used currently by Japanese manufacturers. In Japan, coenzyme Q10 is sold by prescription only.
Coenzyme Q10 is made in the body, but its production declines to suboptimal levels with aging. The nutrient is also known as ubiquinone because of its ubiquitous presence in the body. Recent studies have shown that this antioxidant nutrient may reduce the progression of Parkinson's and Huntington's disease, and that is also helpful to the heart. The National Cancer Institute has stated, "Interest in CoQ10 as a therapeutic agent in cancer began in 1961, when a deficiency was noted in the blood of both Swedish and American cancer patients, especially in the blood of patients with breast cancer. A subsequent study showed a statistically significant relationship between the level of plasma CoQ10 deficiency and breast cancer prognosis."
Lipshutz commented, "Without CoQ10 there is no human life . . . This (compound) affects everyone on the planet. I am hoping to make people more aware as to how important it is to take supplemental CoQ10. For much of the population it can be viewed as an essential 'vitamin.'"
Vitamin D analog enhances radiation therapy
The June 2003 issue of the Journal of Clinical Cancer Research reported that EB 1089, an analog of vitamin D, can destroy radiation-resistant cells that can remain following radiation therapy for breast cancer. Researchers from Dartmouth Medical School utilized a mouse model of breast cancer to compare radiation alone to radiation combined with EB 1089. They found final tumor volumes in the mice who received the combination therapy to be half that of mice who did not receive the vitamin D analog.
Radiation-resistant cells are dangerous, because they can lead to a reccurrence of the cancer being treated. Vitamin D has been found to prevent and treat several types of cancer, but an excess of the vitamin can elevate serum calcium, affecting bone structure. The modified form of the vitamin used in this study causes less of this type of side effect, and is much more readily tolerated by the patient than chemotherapy.
Lead author and assistant research professor at Dartmouth Medical School, Dr Sujatha Sundaram, commented, "The results of our latest study with EB 1089 are very encouraging. The vitamin D analog has proven effective in enhancing radiation treatments in our prior studies with cell cultures and now in live mice. We are eager to push ahead to clinical trials with breast cancer treatments in humans."
Coathor David A. Gewirtz, PhD, of Virginia Commonwealth University Medical Center in Richmond, Virginia, added, "We're always trying to find drugs that will prevent cancer from recurring, yet be less toxic to the patient than the current chemotherapy regimens. We're seeing very encouraging results in cell culture and animal studies when we add vitamin D analogs to radiation therapy."
The authors hope that their findings will prove useful for individuals with radiation-resistant brain and prostate tumors as well.
Branched-chain amino acids improve tardive dyskinesia symptoms
The June 2003 issue of the American Journal of Psychiatry published the findings from Nathan S. Kline Institute for Psychiatric Research in Orangeburg New York that the branched-chain amino acids, leucine, isoleucine and valine, help to control tardive dyskinesia among patients taking antipsychotic drugs. Tardive dyskinesia is a disorder that occurs frequently among long-term antipsychotic drug users, characterized by twitching and other involuntary movements.
Sxity-eight men with tardive dyskinesia randomly received low-dose, medium-dose or high-dose branched chain amino acids or a placebo three times daily for three weeks. The amino acid formula consisted of valine, isoleucine and leucine in a ratio of 3:3:4. Tardive dyskinesia movements were videotaped for analysis. At the study's conclusion, the men who received the high dose exhibited a highly significant decrease in their symptoms compared to the placebo group, with diminishment of symptoms occurring as soon as one week following treatment. Ono other differences were seen between the groups before and after the trial, including changes in blood glucose or medication levels. Mild gastrointestinal symptoms were the only side effects noted.
While blood levels of the branched-chain amino acids were measured after three weeks, an increase in their levels was observed in the groups receiving them. The aromatic amino acids phenylalanine, tyrosine and tryptophan simultaneously declined in these groups and correlated with the decrease in tardive dyskinesia movements, leading the researchers to suggest reduced synthesis of monoamine neurotransmitters (dopamine, noradrenaline, and serotonin) from aromatic amino acid precursors as a possible mechanism of action for isoleucine, leucine and valine against tardive dyskinesia symptomps in this study.
Cooling after cardiac arrest helps heal brain
At the Annual Meeting of the Society of Academic Emergency Medicine held in Boston this year, researchers from the University of Pittsburgh School of Medicine reported that inducing hypothermia following cardiac arrest improves survival and promotes growth factors in the brain that aid in recovery. Cardiac arrest is the sudden loss of heart function that results in death in the majority of cases and in brain injury in many of the survivors.
The researchers found that laboratory animals cooled to 33 degrees Celsius within one hour following cardiac arrest experienced a 100 percent survival rate compared to 75 percent of animals not cooled. Microscopic examination of brain tissue found a 50 percent reduction in brain injury in the cooled group compared to the animals who did not undergo hypothermia. An increased level of glia-cell derived growth factors that support nerve cells were found in the brains of the cooled animals, which may assist in brain recovery. This shows that cooling, rather than merely slowing the injury process, actually stimulates recovery. Additionally, the team observed functional improvement in the cooled group twelve hours following cardiac arrest compared to little functional improvement in animals that had not been cooled.
Assistant professor of emergency medicine at the University of Pittsburgh School of Medicine,.Clifton Callaway, MD, stated, "Although it is known from clinical studies that cooling the brain offers therapeutic benefits to patients, further studies need to be done to determine how much the brain should be cooled and for how long. By understanding the molecular mechanisms of brain recovery in cardiac arrest, we can prescribe a more effective treatment."
Dr Callaway and his colleagues are now routinely cooling cardiac arrest patients at the University of Pennsylvania Medical Center Presbyterian Hospital based on these and previous findings.