Selenium may help protect smokers from lung cancer
The December 2002 issue of the journal Cancer Causes and Control published a study showing that low levels of the trace mineral selenium are associated with a higher risk of lung cancer in male smokers. The examined 500 Finnish men who were part of the Alpha-Tocopherol Beta-carotene Cancer Prevention study, which was conducted between 1985 and 1993. Finland began fortifying agricultural fertilizers in 1984, which increased dietary intake of selenium in its population.
Two hundred fifty participants who had been diagnosed with lung cancer prior to April of 1993, and 250 age-match controls were randomly selected and their body levels of selenium were determined by measuring the levels in toenail samples. Subjects were provided with 50 milligrams alpha-tocopherol (vitamin E), 20 milligrams beta-carotene, both vitamins, or a placebo, on a daily basis throughout the study. The data was analyzed for each year of the study, and the researchers found that men who had the highest levels of selenium had an 80% lower rate of lung cancer than those whose selenium concentrations were the lowest.
Later in the trial, a comparison of the two groups revealed less of a difference, but those whose selenium levels were the highest still had a 39% lower risk. The authors suggested that this finding could be attributable to the lower levels of selenium found earlier in the study due to less exposure to selenium-fortified fertilizers, providing a greater number of participants with very low levels of selenium for comparison. It is also possible that selenium fortification lowered overall lung cancer risk, changing the relationship between selenium and lung cancer in the later years of the study. In addition, it was discovered that vitamin E added to the benefit of selenium in the last year of the trial.
Less fat, not calories, may be responsible for lifespan extension
A study published in the January 24 2003 issue of Science published the finding of Harvard researchers that mice bred to lack insulin receptors in their fat cells had less body fat and lived 18 percent longer than normal mice, despite eating diets that were not restricted in calories. The experiment may provide an explanation for how calorie restriction works and have implications for humans.
The researchers used fat-specific insulin receptor knockout, or FIRKO mice in the study and compared them to three other strains. At three months of age through the remainder of their lives, the FIRKO mice had body weights that were 15 to 25 percent lower than controls as well as a 50 to 70 percent reduction in fat mass. Despite being thinner than the controls, the amount of calories consumed by the FIRKO mice was higher by 55 percent. At thirty months of age, which is an average lifespan for laboratory mice, 80 percent of the FIRKO mice were alive compared to 45 to 54 percent of the mice in the control groups. Maximum lifespan was extended by approximately five months, with the longest lived FIRKO mouse dying at the age of 41 months.
In attempting to formulate a theory in regard to the mechanism of action of calorie restriction, the most common hypothesis has been that consumption of fewer calories and the consequent reduction in metabolism leads to the formation of fewer harmful free radicals, resulting in less oxidative damage to the body. In the FIRCO mice, however, the metabolic rate was increased. The findings show that the increased lifespan of the mice may be due to altered insulin signaling in fat tissue, and that "leanness, not food restriction, is a key contributor to extended longevity." (Bluher M et al, "Extended longevity in mice lacking the insulin receptor in adipose tissue," Science vol 299 pp 572-4)
Glucosamine relieves knee pain
The results of a small trial published in the February 2003 issue of the British Journal of Sports Medicine showed that oral supplementation with glucosamine was largely successful in relieving regular knee pain of unknown origin. The trial enrolled 37 men and 13 women between the ages of 20 and 70. Twenty-two subjects had experienced knee pain for more than ten years. Twenty-four participants received 2000 milligrams glucosamine hydrochloride and 22 received a placebo for twelve weeks. During this time period, subjects were regularly assessed for changes in pain and knee function.
Four participants did not complete the study due to knee surgery during the trial period. The incidences of side effects reported were similar between the placebo and glucosamine groups. The participants who received glucosamine experienced a steady lowering of knee pain scores over the course of the study. After four weeks, over a third of the glucosamine group had some degree of pain relief, increasing to over two-thirds after eight weeks. Eighty-eight percent of subjects receiving glucosamine reported an improvement in knee pain over the study's three month course compared to 17 percent in the placebo group.
This study was unique in that it administered glucosamine over a three month period, compared to other studies lasting four or eight weeks, and the amount of glucosamine, intended to provide 168 grams to each participant over the study's course, was greater than most earlier studies. This may explain why an earlier study supplementing 500 milligrams glucosamine for a two month period failed to show improvement. Since the knee pain experienced by participants in the current study was probably due to cartilage damage or osteoarthritis, glucosamine's proposed mechanism of action of improvement of cartilage integrity was likely the reason for the benefits seen in this study.
Large study shows vitamin D, not calcium, lowers hip fracture risk in women
A prospective analysis of 72,337 postmenopausal women, published in the February 2003 issue of The American Journal of Clinical Nutrition, showed consumption of vitamin D to be protective against hip fractures. Contrary to commonly held beliefs, neither milk consumption nor calcium intake appeared to be preventive.
The subjects were part of the Nurses' Health Study, which enrolled 121,700 female nurses in 1976. Information concerning diet and hip fracture incidence was provided by mailed-in questionnaires. Over the course of the eighteen year study, 603 hip fractures were identified.
From the data provided, the Harvard researchers calculated the daily amounts of calcium and vitamin D obtained by the participants. In the final analyses, calcium intake from food and supplements or from diet alone was not associated with hip fracture incidence, while vitamin D, when consumed in the amount of 12.5 micrograms per day or more from diet and supplements, was associated with a 37% lower risk of hip fracture compared to consuming less than 3.5 micrograms per day. When dietary vitamin D alone was examined, consuming 6.25 micrograms or more per day was associated with a 43% lower risk of hp fracture than consumption of less than 2.5 micrograms per day. Milk consumption did not reveal an inverse association with hip fractures, but consumption dark fish, such as salmon, was associated with a 33% lower risk of hip fracture when eaten more than once per week compared to less than once per month, presumably because of its vitamin D content.
The authors conclude that, "Because women commonly consume less than the recommended daily intake of vitamin D and additional exposure to sunlight can increase the risk of skin cancer, use of supplements or more frequent consumption of dark fish may be prudent." (Feskanich D et al, "Calcium, vitamin D, milk consumption and hip fractures: a prospective study among postmenopausal women, Am J Clin Nutr 2003;77:504-11)
Fish oil plus GLA more effective in improving blood lipids
Researchers from the University of Guelph, in Guelph, Ontario, tested the fish oil derived omega 3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) alone and in combination with the omega 6 fatty acid gamma linolenic acid (GLA) , with the goal of determining their effect on plasma lipids. Thirty-one women aged 36 to 68 were given a daily supplement providing 4 grams EPA and DHA combined with 0, 1, 2 or 4 grams GLA for twenty-eight days.
While there was only a slight reduction in serum total cholesterol experienced by all groups after 28 days on the regimens, there was a significant lowering of serum low density lipoprotein (LDL) concentrations in the groups receiving regimens containing 2 and 4 grams GLA. The group receiving 2 grams GLA experienced the largest mean reduction in non-HDL cholesterol. Mean high density lipoprotein (HDL) concentrations were significantly higher in both groups consuming fish oil alone or with 1 gram GLA after twenty-eight days compared to presupplementation levels. Triglycerides were lowered significantly in all groups but the last. While total omega-3 fatty acids increased in all groups, dihomo-gamma-linolenic acid (DGLA) increased significantly in serum phospholipids only I the groups receiving two and four grams of GLA. DGLA is an omega 6 precursor fatty acid that generates anti-inflammatory substances in the body.
The fact that the addition of 2 grams GLA to EPA and DHA caused a significant reduction in LDL cholesterol was of note because fish oil alone usually does not effect LDL concentrations. Subjects in the group receiving 2 grams GLA experienced a 43% reduction in myocardial infarction risk, the highest of all the groups in this study.
The research was published in the January 2003 issue of The American Journal of Clinical Nutrition (http://www.ajcn.org/)
Vitamin E succinate suppresses melanoma
The December 2002 issue of the Annals of Surgical Oncology published news that vitamin E succinate, a natural form of the vitamin, helps put melanoma tumor cells in a dormant state, and inhibit the formation of new blood vessels, a process known as angiogenesis. Relapse after the excision of melanoma tumors accounts for the majority of deaths from melanoma. In this report, the researchers showed success in vivo for D-alpha-tocopherol succinate against the disease.
The researchers injected one ten mice with 100 milligrams per kilogram vitamin E succinate per day for seventeen days immediately following inoculation with melanoma tumor cells while another group received the vitamin 17 to 25 days following inoculation, and two control groups received injections of sesame oil for corresponding time periods. When the first group were examined after seventeen days, tumor volume was an average of nearly ten times as small as that of the controls. Vitamin E succinate treatment initiated 17 days following melanoma inoculation reduced tumor volume by more than half compared to the control group. Tumors in the groups treated with the vitamin showed an average of 87 percent fewer microvessels, demonstrating suppression of angiogenesis by vitamin E succinate whether it was given early or later during melanoma growth. It was found that vascular endothelial growth factor (VEGF) and vascular endothelial growth factors receptors 1 and 2 were significantly suppressed in the tumors of the animals who received the vitamin. Additionally, VEGF promoter activity was found to decrease linearly with increased vitamin e succinate dosage.
The study demonstrates that melanoma growth and angiogenesis are reduced by vitamin E succinate, at least in part by the inhibition of VeGF transcription. A study conducted in 1996 also showed an antiangiogenesis effect for vitamin E succinate against squamous cell cancer in hamsters.
Large study shows aspirin use associated with lower breast cancer incidence
The December 2002 issue of the journal Cancer Epidemiology, Biomarkers & Prevention, published the results of a study of 27,616 postmenopausal women that revealed that aspirin, but not other nonsteroidal anti-inflammatory drugs (NSAIDs), was associated with a reduction in the risk of breast cancer, and that the risk decreased as the frequency of aspirin use increased. Previous epidemiologic studies have demonstrated a reduction in breast cancer risk with NSAID use but did not separate the effects of aspirin from other NSAIDs. These studies also failed to account for breast cancer risk factors.
The study involved participants in the Iowa Women's Health Study, aged 55 to 69, who were followed for six years, during which 983 cases of breast cancer were identified. Information on aspirin and NSAID use, hormone replacement therapy, smoking status and alchohol intake was obtained via questionnaires completed by mail in 1992. Data concerning other risk factors, such as body mass index, age at menarche, number of children, age at first live birth and age at menopause, was obtained at the study's onset. The women were followed until the end of 1999.
After accounting for age and other breast cancer risk factors, the use of two to five aspirin per week was associated with a 20% reduction in the risk of breast cancer compared to those who did not report current usage of the drug. Women who used six or more aspirin per week further lowered their risk. The greatest risk reduction associated with aspirin use was seen in late stage disease and in situ breast cancer. Non-aspirin NSAIDs were not associated with a reduction in breast cancer incidence.
The authors predict that "use of aspirin containing compounds could have a significant public health impact" if it truly reduces breast cancer risk.
(Johnson TW, Anderson KE, Lazovich D et al, "Association of Aspirin and Nonsteroidal Anti-inflammatory Drug Use with Breast Cancer," Cancer Epidemiology, Biomarkers & Prevention, vol 11, 1586-91.)
Antioxidants and arginine protect blood vessel walls
A study published online in the Proceedings of the National Academy of Science on January 13 2003 showed that vitamins C and E and the amino acid L-arginine help protect the walls of the blood vessels from the continual stress of rapidly flowing blood. The walls of blood vessel branch points are exposed to greater shear-stress, resulting in cell damage and inflammation with consequent early plaque formation and blood flow impediment.
The researchers cultured human coronary endothelial cells and exposed them to shear-stress of a force similar to that experienced in the veins and arteries, in the presence and absence of a combination of alpha-tocopherol and ascorbic acid, and/or L-arginine. The increased shear-stress caused an increase in inflammatory factors and decreased expression of endothelial nitric oxide synthase (eNOS), a molecule that promotes the formation of nitric oxide, which dilates blood vessels and protects against clotting. The addition of the vitamins or L-arginine increased eNOS, with a synergistic action observed when they were used together. Inflammatory proteins were reduced as well with by antioxidants alone or in combination with L-arginine.
In vivo, mice fed a high cholesterol diet for six months were divided into groups that were supplemented with vitamins C and E, L-arginine, or a combination of these therapies, for one or eight weeks. A control group received no supplementation. After six months, the control mice had developed advanced atherosclerotic lesions in areas of increased shear-stress, and intermediate lesions in areas less prone to the condition. While one week of treatment with antioxidants and/or L-arginine did not effect lesion formation, the mice who received the treatments for eight weeks experienced reduced lesions in both areas. Treatment with the supplements increased eNOS and decreased inflammatory factors after both one and eight weeks.
These findings point to a synergistic effect between vitamins C and E and L-arginine in protecting blood vessels.
Selenium protects brain cells from excitotoxicity
In a report published in the January 2003 issue of Federation of American Societies for Experimental Biology journal, German researchers discovered that a deficiency of the trace mineral selenium increases the susceptibility of brain cells to excitotoxicity induced by the excitatory neurotransmitter glutamate. The occurrence of brain lesions associated with excitotoxicity such as epilepsy and stroke is followed by massive free radical activity and the activation of factors leading to apoptosis, or programmed cell death.
Using a neuronal cell line, the researchers created an excitotoxic condition by administering glutamate, which caused the death of over 80 percent of the cells. When selenium in the form of sodium selenite was administered at the same time, cell death was prevented in a concentration-dependent manner. Even when added hours after glutamate damage was induced, selenium was able to prevent cell death caused by glutamate. It was found that high levels of glutamate in neurons resulted in excessive levels of peroxides. Treatment with selenium prevented this from occurring without effecting glutathione levels. Another form of selenium, sodium selenate, was also found to be effective, even though it does not have direct antioxidant effects, but is incorporated into selenoproteins. Further investigation determined that it is selenium-containig proteins that are involved in antiapoptotic mechanisms.
To test the findings in vivo, rats were given a diets providing adequate or deficient selenium. Rats on the selenium deficient diets showed a dramatic reduction of selenium in the liver and an approximately 10% lower level of the mineral in the brain than those who received sufficient amounts. When excitotoxicity was induced, the rats fed the selenium-deficient diets experienced significantly more seizures than the rats who were not deficient.
The authors speculate that a deficiency in selenium may also effect glial cells, in addition to neurons. They recommend that prevention of excitotoxic brain damage should not rely on the substitution of other antioxidants but should consider selenium levels as an independent factor.
Calorie restriction protects brains
A Federation of American Societies for Experimental Biology online publication showed that restriction of calories, known to slow many of the aspects of aging of the body, may protect the brain from aging as well. In research supported by National Institutes of Health and the National Institute of Aging, investigators at the University of Florida compared male rats who were allowed to eat all they wanted for twelve or twenty six months to rats who received 40 percent fewer calories for twenty-six months.
Upon examination of the rats' frontal cortexes, the researchers found an elevation in cytochrome-C, a protein associated with apoptosis (programmed cell death) when the cell's mitochondria become damaged, in the brains of the older nonrestricted rats, but did not find a corresponding elevation in the brains of the rats who received the calorie restricted diets. Specific DNA fragmentation indicative of apoptosis, increased as well in the unrestricted groups, but was significantly lower in the restricted animals. Additionally, an apoptosis repressor protein known as ARC which protects against cell death was found to be twice as high in the calorie restricted rats compared to those who received ad lib diets.
The study is the first to examine the effects of life-long calorie restriction on the brain's neurons. Coauthor and director of the Biochemistry of Aging Laboratory at the University of Florida College of Health and Human Performance, Christiaan Leeuwenburgh, commented, "In normal aging, there's a variety of factors that could alter the internal environment of the cell and make it more prone to die. We would like to stop this. Cells in neurons, muscle and heart have very low regenerative capacity, so obviously you don't want to lose a lot of them."
Vitamin C and taurine reverse blood vessel constriction in smokers
In a study published online in the January 6 2003 rapid access issue of Circulation: Journal of the American Heart Association, researchers from Beaumont Hospital, in Dublin, Ireland, found that vitamin C and the amino acid taurine improved endothelial-dependent vasodilation in smokers. Endothelial dysfunction initiated by monocyte-endothelial interactions has been observed in chronic cigarette smokers, and is an early sign of atherosclerosis.
Fifteen smokers and fifteen nonsmokers between the ages of 20 and 37 were recruited for the study. The smokers received 2 grams vitamin C or 1.5 grams taurine daily for five days followed by a two-week "wash-out" period before switching regimens for five additional days. Blood vessel function was assessed by ultrasound examination at the beginning of the study and after treatment with the supplements.
It was found that the blood vessels of smokers were smaller than nonsmokers at the study's onset and that their ability to dilate was less than that of nonsmokers. While vitamin C improved the smoker's blood vessel function, taurine restored it to that of nonsmokers.
In vitro it was found that human endothelial cells cultured with monocyte-conditioned medium taken from smokers showed impaired nitric oxide release, but pretreating the smokers with taurine prevented this.
Senior author and professor of surgery at the Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, David J. Bouchier-Hayes, MD, explained, "When blood vessels are exposed to cigarette smoke it causes the vessels to behave like a rigid pipe rather than a flexible tube, thus the vessels can't dilate in response to increased blood flow . . . We're not trying to find a therapeutic treatment for smoking, because we believe that the best therapy for smokers is to stop smoking. Nonetheless, smokers provide a good clinical model for treatment of endothelial dysfunction."
Review finds protective benefit for aspirin against esophageal cancer
A review and meta-analysis published in the January 2003 issue of the journal Gastroenterology, concluded a protectiive association between aspirin and nonsteroidal anti-inflammatory drug (NSAID) use and esophageal cancer risk. Other studies have associated the use of aspirin and NSAIDs with a lowered risk of colon cancer and possibly stomach, lung and breast cancers.
Out of 98 potential studies retrieved from a MEDLINE search, University of California researchers selected nine that met their criteria, which provided a total of 1813 patients with esophageal cancer for analysis. Studies were included if they evaluated exposure to aspirin or NSAIDS, measured esophageal cancer diagnoses or deaths, and reported a relative risk or odds ratios, or provided other data to allow their calculation.
It was found that subjects who had any exposure to aspirin or NSAIDs experienced a 43 percent reduction in the risk of developing either type of esophageal cancer (esophageal adenocarcinoma or esophageal squamous cell cancer) compared to nonusers. Frequent aspirin or NSAID use increased the risk reduction to 46 percent, while even intermittent use provided a reduction of 18 percent. When aspirin was examined separately, risk reduction increased to 50%, appearing to offer greater protection than NSAIDs.
These results support further studies of the ability of aspirin or NSAIDs to prevent esophageal cancer in high risk populations such as patients with Barrett's esophagus, who have forty times the risk of esophageal adenocarcinoma than those without the condition. The drugs' mechanism of action may be their ability to inhibit the cyclooxygenase-2 enzyme, which is involved in the early development of esophageal and other tumors and, when elevated, has been found to be associated with Barrett's esophagus. Additionally, aspirin and NSAID use may prevent the development of Barrett's esophagus by decreasing the inflammation of its precursor, gastroesophageal reflux disease.
Aspirin, beta blockers underprescribed for heart patients
A study conducted at Stanford University Medical Center, published in the January 1 2003 issue of the Journal of the American College of Cardiology revealed that despite studies showing that aspirin and other drugs can help manage heart disease, physicians continue to underprescribe them. Randall Stafford MD, PhD of Stanford University Medical Center and David Radley of Yale University analyzed thirteen years of data from the National Disease and Therapeutic Index and the National Ambulatory Medical Care Surveys to determine the utilization of aspirin and beta blockers for coronary artery disease, warfarin for atrial fibrillation and ACE inhibitors for congestive heart failure.
Although prescription rates for the drugs rose during the previous decade, usage rate increases later slowed and are currently well below recommended levels, with warfarin use for atrial fibrillation at 58 percent, beta-blocker and aspirin use for coronary artery disease at 40 and 38 percent, and ACE inhibitors for congestive heart failure at 39 percent.
Dr Stafford, who is an assistant professor of medicine at the School of Medicine and at Stanford's Center for Research in Disease Prevention, "There is no dispute over the benefit of these medications. The medications lead to a reduction in complications and a delay in progression of disease. There is debate over the optimal usage level of each medication - and clearly the number is less than 100 percent. But the level of use for each should be above 50 percent and probably closer to 80. Adoption of these therapies has been slow to even approach acceptable levels. Physicians are taught to do no harm and may withhold therapy that actually has more benefits than risks . . . This suggests that patients may need to be their own advocates and make sure that these medications are a topic of conversation with their physicians."