St John's wort compound inhibits HIV gene expression
A report published online on October 27 in the journal Gene Therapy revealed that a protein found in the herb St John's wort (Hypericum perforatum) inhibits the expression and replication of the human immunodeficiency virus 1 (HIV-1) genome. Expression of the gene and the replication of the viral genome results in the development of AIDS in people infected with HIV.
Director of the Center for Neurovirology at Temple Univeristy School of Medicine in Philadelphia, Kamel Khalili, PhD, and colleagues found that an extract from St John's wort was able to inhibit HIV-1 gene expression in cells infected with the virus. They identified a protein, named p27SJ, as responsible for the antiviral activity. "It has unique characteristics," Dr Khalili commented. "Remember, it is a plant protein, and so far, to my knowledge, there is no similar protein to that in mammalian cells."
"Our studies indicate that p27SJ has the capacity to inhibit expression of the HIV-1 gene by interacting with both cellular proteins and viral proteins," Dr Khalili explained. "Since HIV-1 gene expression relies heavily on these factors, p27SJ can block viral replication by interfering with the proteins recruited by HIV-1 to increase viral gene expression."
It is unknown whether the p27SJ protein is present in the St John's wort preparations available as dietary supplements. Dr Khalili added, "We don't know yet how we have to deliver the protein to cells infected with HIV-1. Even if the protein were present in the tablets, we don't know how much might be present and whether the protein would be effective when ingested."
Proanthocyanidins from cranberry inhibit tumor growth
The October 17 2005 issue of the Journal of Science and Food Agriculture reported that compounds isolated from cranberries help prevent the growth of tumors when studied in cell cultures.
Catherine C. Neto of the University of Massachusetts and colleagues tested a proanthocyanidin rich fraction of cranberry as well as separate proanthocyanidins on breast, prostate, cervical, lung, and colon cancer cell lines as well as a melanoma and leukemia cell line, and normal mouse cells. Antitumor activity was expressed as the concentrations of a sample that inhibits cell growth by 50 percent relative to untreated cells. High and low concentrations of whole cranberry extract and cranberry fractions were also tested for their ability to inhibit matrix metalloproteinases (MMPs) in prostate cancer cells. Matrix metalloproteinases are enzymes that can break down intercellular tissue, which can increase the tumor invasiveness and metastasis.
The scientists found that proanthocyanidins were effective at inhibiting lung, cervical and colon cancer as well as leukemia growth. Additionally, one of the subfractions was found to inhibit all but the cervical tumor line as efficiently as its parent compound. Other subfractions inhibited tumor growth at higher concentrations.
Whole cranberry extract inhibited matrix metalloproteinase-2 and 9, particularly at higher concentrations. The higher concentration of proanthocyanidins inhibited MMP-2 completely and MMP-9 by 75 percent. The study is the first to evaluate cranberry proanthocyanidins' effect on MMPs.
The authors concluded that the proanthocyanidin-rich fraction from cranberries inhibited the proliferation of lung, colon and leukemia cell lines at concentrations below that which inhibited normal mouse fibroblasts. They write, "In light of our findings as well as previously published reports, cranberries may inhibit carcinogenesis in a variety of ways and further study is needed to reveal the mechanisms associated with each of its active phytochemicals."
Bioflavonoid helps inhibit prostate cancer
In a report published online on October 18 2005 in the FASEB (Federation of American Societies for Experimental Biology) Journal, researchers from Case Western Reserve University in Cleveland revealed that the bioflavonoid apigenin offered protection against prostate cancer tumor growth in mice. Apigenin is found in a number of fruits and vegetables as well as the herbs chamomile, lemon balm, perilla and parsley.
Assistant professor at the Case School of Medicine Department of Urology, Sanjay Gupta PhD and colleagues orally administered a low or high dose of apigenin or an inert substance to groups of mice for ten weeks. After two weeks of treatment, prostate tumors were implanted in each mouse. A second experiment designed to assess apigenin's efficacy as a treatment,administered the compound from two weeks following tumor implantation until the study's conclusion.
The research team found that mice that received apigenin experienced a reduction in tumor volume and weight with animals who received the higher dose experiencing the greatest benefit. The higher dose of apigenin resulted in a 59 percent inhibition in tumor volume in the first experiment, and in a 53 percent inhibition in the second experiment compared to growth observed in the control animals. Dr Gupta and colleagues also found an associated between apigenin and decreased insulin-like growth factor (IGF-1) levels, which, when elevated, is associated with an increased risk of prostate and other cancers. Conversely, insulin-like growth factor binding protein levels, which reduce these same cancer risks, was increased in the animals who received apigenin.
Dr Gupta concluded, "Apigenin may prove useful in the prevention and therapy of prostate cancer by shutting off the IGF signaling that leads to prostate cancer cell growth and/or development. Our findings suggest that apigenin could be developed as a promising agent against prostate cancer."
Greater omega-3 fatty acid intake associated with reduction in dry eye syndrome
A report published in the October 2005 issue of the American Journal of Clinical Nutrition revealed that a greater intake of omega-3 fatty acids is associated with a decreased risk of dry eye syndrome, and having a higher amount of omega-6 fatty acids in the diet is increases the risk of the condition.
Researchers at Brigham and Women's Hospital and Schepens Eye Research Institute examined data from 32,470 participants in the Women's Health Study, which is evaluating the effects of aspirin and vitamin E on cancer and cardiovascular disease prevention among female health professionals. Food frequency questionnaires completed upon enrollment provided information on omega-3 and omega-6 intake, and participants were queried concerning whether they had been diagnosed with dry eye syndrome at the four year follow-up.
The team found that women whose omega-3 intake was in the top one-fifth of participants experienced a 17 percent lower risk of dry eye syndrome than women whose intake was in the lowest fifth. Having a greater than 15 to 1 ratio of omega-6 to omega-3 fatty acids in the diet more than doubled the risk of dry eye.
The study is the first of its kind to examine modifiable risk factors for dry eye. Lead author Biljana Miljanovic, MD, of the Divisions of Preventive Medicine and Aging at Brigham and Women's summarized, "We found that a high intake of omega 3 fatty acids, often referred to as a 'good' fat, commonly found in fish and walnuts, is associated with a protective effect. Conversely, a higher ratio of omega 6, a fat found in many cooking and salad oils and animal meats, compared to omega 3 in the diet, may increase the risk of dry eye syndrome."
CLA dampens inflammation
Researchers at the University of Wisconsin at Madison have discovered that an isomer of conjugated linoleic acid (CLA), a group of fatty acids found in milk and other foods, helps regulate cyclooxygenase-2, or COX-2, a protein that plays a role in inflammation such as occurs with arthritis or cancer. CLA exists in a number of structural forms known as isomers, some of which have been found to be of more benefit than others. The finding was published in the October 2005 issue of the Journal of Lipid Research.
Study author and professor of animal science at the University of Wisconsin's College of Agricultural and Life Sciences, Mark Cook and colleagues determined that one of CLA's isomer's inhibits the COX-2 protein by blocking an important cellular pathway. Dr Cook stated, "It's clear from previous research that conjugated linoleic acid, or CLA, prevents inflammatory damage resulting from immune response. We've identified the biochemical mechanism by which this occurs."
Dr Cook's interest in CLA resulted from his investigation into the reason why an animal in an environment that is free of microbes grows faster than one raised in a conventional environment. Antibiotic usein animal agriculture improves weight gain by protecting the body from immune responses that fight disease but result in inflammation, muscle wasting and appetite loss. Although antibiotic use has benefitted the industry, concerns exist regarding the long-term devleopment of of antibiotic resistance. Dr Cook believes that CLA could be used as a natural compound to prevent damage from the immune system's response to invaders. "The ideal solution is to let the immune system fight bacteria, but at the same time to maintain the overall health of the system," he stated.
A future study is planned to find out if the isomer can be increased in milk products by changing the diets of the dairy cows.
Low copper levels linked with cognitive decline in Alzheimer's disease
Head of the Division of Neurobiology at Saarland University Medical Center in Germany, Professor Thomas Bayer, and his German colleagues measured plasma copper levels in 32 men and women with mild to moderate Alzheimer's disease. After eight weeks the patients were tested for cognitive function utilizing the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), and copper levels were reassessed. For the analysis, the researchers grouped the participants according to low, medium or high plasma copper levels, defined as levels between 65 and 98, 99 and 132 and 133 to 165 micrograms per deciliter copper.
Although copper levels were within the normal physiologic reference points, participants in the low copper group had significantly higher ADAS-cog scores (which indicate a greater number of errors and lower performance) than those of the group with medium copper levels. The discovery agreed with previous research findings which found decreased superoxide dismutase-1 activity in a group of 44 Alzheimer's patients, an indicator of decreased cellular copper levels.
The authors conclude that "Alzheimer's disease patients suffer from a mild copper deficiency, as has been expected from analyses of Alzheimer's disease mouse models." Dr Bayer and colleague Dr Frank Pajonk, who is a psychiatrist at Saarland University Medical Center's Department of Psychiatry are currently conducting a clinical trial to assess the potential benefit administering copper orotate with a cholinesterase inhibiting drug for one year to patients with mild to moderate Alzheimer's dementia. The study will include examination of blood and cerebrospinal fluid, and magnet resonance imaging of the brain, and its outcome will be the subject of a future report.
Fibrinogen levels linked with cardiovascular disease, mortality
A review published in the October 12 2005 issue of the Journal of the American Medical Association concluded a positive association between fibrinogen levels and vascular and nonvascular mortality. Fibrinogen is the precursor of fibrin, which is a determinant of blood viscosity and platelet aggregation.
The Fibrinogen Studies Collaboration of Cambridge University in England reviewed information from 31 studies involving 154,211 participants with no known history of coronary heart disease or stroke upon enrollment. Fibrinogen levels and other measurements were determined at the beginning of the studies and the subjects were followed for at least one year. There were 13,210 deaths, and 6,944 first nonfatal heart attacks or strokes during the studies' follow-up periods. Three thousand nine hundred forty-one of the deaths were due to vascular causes, 8,007 to nonvascular causes (including cancer) and 1,262 to unknown causes.
A linear association with usual fibrinogen levels and the risk of any coronary heart disease (CHD), stroke, vascular and nonvascular mortality was determined in all age groups studied (ages 40-59, 60-69 and 70 and older). Every 1 gram per liter increase in usual fibrinogen level was associated with a more than two times increased risk of fatal and nonfatal coronary heart disease, stroke, and deaths from vascular and nonvascular causes.
The authors write that their meta-analysis "provides the first reliable demonstration that fibrinogen is associated with the age-specific incidence rates of CHD, stroke (especially nonhemorrhagic stroke), other vascular mortality, and, interestingly, of the aggregate of all nonvascular causes (mainly comprising cancer)." The authors write that determining whether fibrinogen has a causative effect with disease will require particular research strategies or involve randomized trials of fibrinogen-lowering drugs.
Eating fish reduces rate of cognitive decline to equivalent of being 3-4 years younger
An early release published online in the American Medical Association journal Archives of Neurology revealed that eating fish at least once per week is associated with a 10 percent slower yearly decline in cognitive function among older individuals.
Martha Clare Morris, ScD, and colleagues at Rush University Medical Center in Chicago analyzed data obtained from participants in the Chicago Health and Aging Project, an ongoing study of 6,158 men and women aged 65 and older that was initiated from 1993 to 1997. Participants completed food frequency questionnaires and underwent cognitive testing at the beginning of the study. At least two cognitive assessments were conducted every three years during the six year follow up.
The team found that consuming fish at least once per week was associated with a 10 percent lower rate of cognitive decline per year than that experienced by those ate fish less frequently. Among those who consumed two or more meals containing fish per week, the rate was 13 percent slower. The authors note that this rate reduction is the equivalent of being three to four years younger in age.
The authors observed, "Cognitive decline is common among older people and is very much associated with advancing age. Our data offer no insight as to whether this cognitive decline is pathological or the result of a normal aging process. Nonetheless, data from the United States and other countries indicate that it is a widespread and increasing public health problem."
"This study suggests that eating one or more fish meals per week may protect against cognitive decline associated with older age." they conclude. "More precise studies of the different dietary constituents of fish should help to understand the nature of the association."
Meta-analysis finds 800 microgram folic acid supplementation most effective to lower homocysteine
The results of a meta-analysis published in the October 2005 issue of the American Journal of Clinical Nutrition found that taking at least 800 micrograms folic acid per day in combination with vitamin B12 is necessary to achieve the greatest reduction in homocysteine levels. Many multinutrient supplements provide just 400 micrograms folic acid, although fortified foods contribute to daily intake.
The meta-analysis was the fruit of the Homocysteine Lowering Trialists' Collaboration, which was established to determine the amount of homocysteine reduction achieved with varying doses of folic acid and vitamins B6 and B12. The current analysis examined data from 2,596 participants in 25 trials in which the effect of the vitamins on homocysteine levels was investigated.
When daily doses of 200, 400, 800, 2000 and 5000 micrograms folic acid were analyzed, it was found that 800 micrograms provided a significantly greater reduction in plasma homocysteine compared to 400 micrograms. Supplementation with 800 micrograms folic acid per day was associated with a 23 percent reduction in homocysteine, compared to a 20 percent reduction associated with 400 micrograms. Similarly, 400 micrograms had more impact than 200 micrograms, which was associated with a 13 percent reduction. Two thousand micrograms folic acid per day appeared to provide the same benefit as 800 micrograms, and 5000 micrograms provided a slightly greater benefit. While the addition of 400 micrograms per day vitamin B12 was associated with a 7 percent further reduction of homocysteine levels, vitamin B6 did not appear to have an effect.
The authors conclude that "little further homocysteine reduction is achieved by increasing the dose of folic acid above approximately 0.8 milligrams per day, but combined administration of folic acid with vitamin B12 will achieve a greater reduction in plasma homocysteine concentration than dose that of folic acid alone."
Vitamin D deficiency widespread
Vitamin D researcher Michael F Holick of the Department of Medicine at Boston University Medical Center and colleagues examined data on 8,276 individuals aged one year and older. Average daily vitamin D intake from food and from food plus supplements was calculated from dietary recall interviews.
Dr Holick and his colleagues found that among children aged one to eight, Mexican American children had the highest intake of vitamin D, although 31 percent did not meet of exceed adequate intake (AI) levels. Fifty-nine percent of non-Hispanic Caucasian children in this age group were considered to have an adequate intake of the vitamin, yet less than half of African-American children had their vitamin D needs met. When food combined with supplements was considered, these figures improved to 82 percent of Mexican American, 78 percent of non-Hispanic Caucasian and 66 percent of African Americans meeting adequate intake levels.
The percentage of individuals who had an adequate intake of vitamin D was found to decline with age, so that by the age of 51, 96 percent of the participants in that age category had a deficient intake from food alone. The authors recommend, "As an alternative to greater sun exposure, increasing the availability of fortified foods, supporting greater use of dietary supplements, and encouraging changes in dietary patterns to consume more food fortified with vitamin D should be considered to address this important health issue."
Weight gain linked with risk of prostate cancer recurrence
A report published in the journal Clinical Cancer Research's October 1 2005 issue revealed a correlation between rapid weight gain after the age of 25 and an increased risk of recurrence of prostate cancer following surgical removal of the gland. Obesity at age 40 or older was also discovered to increase recurrence risk.
The current study evaluated data from 526 men registered at the University of Texas M. D. Anderson Cancer Center who had undergone prostatectomies due to cancer . During the 54 month follow up period, 18 percent of the men experienced biochemical failure, defined as an elevation in prostate specific antigen (PSA), a marker of cancer that is produced primarily by the prostate gland.
The M.D. Anderson team found that men who were obese upon diagnosis experienced an increased rate of biochemical failure during the follow up period compared to nonobese men. Those who were obese at age 40 had an even greater risk, with twice the likelihood of experiencing a rise in PSA than that observed in men who were not obese. Rapid weight gain between the ages of 25 and 40 was also found to be linked with an increased risk compared to men who gained weight more slowly.
Lead author Sara S. Strom, PhD, who is an associate professor at the department of Epidemiology at M. D. Anderson, stated, "Patients who gained an average of three and a half pounds a year have an increased risk for having their prostate cancer recur." She noted, "Urologists and oncologists can use this information when a man is diagnosed with prostate cancer to develop treatment strategies for that patient. By plugging in the clinical characteristics, they calculate each patient's risk of having more aggressive disease that will progress. Body mass index makes that information more precise."
Phytoestrogens help prevent lung cancer
The study included 1,674 lung cancer patients and 1,735 healthy controls matched for gender, age, ethnicity and smoking status, who had taken part in an ongoing study of lung cancer. Dietary questionnaires completed by the participants were analyzed to determine the amount of total phytoestrogens consumed, as well as intake of individual classes of phytoestrogens (isoflavones, lignans, coumesterol and phytosterols) and their members.
Participants whose phytoestrogen intake from food (not including beverages) was among the highest 25 percent had a 46 percent reduced risk of developing lung cancer compared to individuals whose intake was in the lowest fourth. When classes of phytoestrogens were examined, men who consumed the most soy isoflavones had a 72 percent lower risk of lung cancer than those whose intake was lowest. While the use of hormone replacement therapy (HLRT) was associated with a 26 percent reduction in women's lung cancer risk, the reduction was doubled among women who also had a high intake of lignan metabolites..
This study is the largest case-controlled investigation to date to evaluate the effect of dietary phytoestrogens and lung cancer risk among Americans. Lead researcher and chair of M.D. Anderson's Department of Epidemiology Margaret Spitz, MD, commented, "The best cancer prevention advice continues to be to stop smoking, and it is clear that all of us can benefit from healthy eating and exercising. Still, our results generally show that higher intake of these foods resulted in lower lung cancer risk, and that is certainly a tantalizing preliminary finding."