April 28, 2006
Research shows how oxidative stress leads to nonhereditary degenerative brain disease
A report published in the April 21, 2006 issue of the Journal of Biological Chemistry revealed the findings of Emory University School of Medicine researchers that a protein known as DJ-1, which, when mutated, results in hereditary Parkinson's disease, is also involved in nonhereditary (sporadic) Parkinson's disease when it becomes damaged by oxidative stress. Approximately 90 percent of Parkinson's disease cases are believed to be nonhereditary. "One popular theory has suggested that these sporadic cases result from exposure to environmental toxins, such as herbicides or pesticides," lead author and associate professor of pharmacology Lian Li, PhD, observed. "Previous research has indicated that these toxins lead to oxidative stress. While oxidative stress does occur naturally as humans age, further oxidation caused by toxins may overwhelm the body's antioxidants. This theory has been around for a long time. But what's been damaged by this oxidative stress?"
Doctor Li's team examined DJ-1 oxidation levels in the brains of individuals with nonhereditary Parkinson's and Alzheimer's disease, and age-matched controls and found that the protein showed signs of oxidative damage in the brains of the diseased patients. As in hereditary Parkinson's, structural changes to the protein leads to its loss and degradation. "The protein unfolds and cannot function normally," Dr Li explained. "Not recognizing the unfamiliar shape, the protein is broken down by the cell. The end result is the same: you lose your protein. Any mutation or modification causing this protein to lose its function will then lead to neurodegeneration in Parkinson's disease."
Dr Li is researching the possibility that DJ-1 could function as an antioxidant, leaving the cell vulnerable to oxidative damage when the protein is mutated. Until drugs are developed that target DJ-1, Dr Li notes that green tea and vitamin C are good dietary sources of antioxidants.
April 26, 2006
Inflammation and endothelial dysfunction responsible in part for increased cardiovascular mortality among diabetics
The authors of a study published in the May 1, 2006 issue of the journal Arteriosclerosis, Thrombosis and Vascular Biology estimate that 43 percent of the increased cardiovascular mortality that occurs with type 2 diabetes (T2D) is due to inflammation and endothelial dysfunction, rather than conventional cardiovascular risk factors such as hypertension, obesity and disordered lipids.
Researchers in the Netherlands evaluated 631 participants in the Hoorn study, a study of glucose tolerance and cardiovascular disease in men and women aged 50 to 75. Subjects were examined upon enrollment and followed up for an average of 11.7 years during which the cause of any deaths was ascertained. Blood samples were tested for markers of endothelial dysfunction and low-grade inflammation as well as homocysteine, cholesterol, and triglycerides. Additionally, data on blood pressure, weight, height, smoking status, glucose tolerance and other factors was obtained. Participants were classified as having normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes.
Low-grade inflammation was associated with both type 2 diabetes and impaired glucose metabolism, while endothelial dysfunction was associated only with diabetes. Over the follow-up period, low-grade inflammation increased the risk of cardiovascular mortality by 43 percent. Among diabetics, the presence of endothelial dysfunction was associated with an 87 percent higher risk of cardiovascular mortality compared to those without the condition.
"T2D-associated endothelial dysfunction and low-grade inflammation can explain approximately 43% of the higher cardiovascular mortality risk conferred by T2D," the authors conclude. "These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially in T2D, for which endothelial dysfunction is particularly ominous and for which both endothelial dysfunction and low-grade inflammation are highly prevalent."
April 24, 2006
Fiber intake associated with CRP reduction
A report published in the April, 2006 American Journal of Clinical Nutrition revealed an association between increased fiber intake and a reduction in C-reactive protein levels. C-reactive protein (CRP) is a marker of inflammation which scientific evidence has increasingly implicated as a predictor of coronary heart disease. CRP has also been associated with diabetes and the metabolic syndrome which can precede or include the disease.
Researchers at the University of Massachusetts evaluated information obtained in the Seasonal Variation of Blood Cholesterol Levels Study (SEASONS), which collected quarterly data on CRP, diet and other factors from 641 adults over a one year period. Five hundred twenty-four participants with an average age of 48 years were included in the current analysis. Dietary information was obtained at the beginning of the study and at four additional periods during the year.
Average fiber intake during the study was 16.11 grams per day, and the average C-reactive protein was 1.78 milligrams per liter. Eighteen percent of the study population had a CRP value of over 3 milligrams per deciliter, which is considered to be elevated. Those whose total fiber intake was in the top one-fourth of participants had a 63 percent lower risk of having an elevated CRP level than those whose intake of fiber placed them in the lowest fourth. The inverse association held true for soluble as well as insoluble fiber, however insoluble fiber appeared to have a stronger inverse association with CRP elevation.
These results add to those of two earlier epidemiologic studies which used data derived from NHANES 1999-2000 that found an inverse association between fiber intake and serum C-reactive protein levels. The authors of the current study recommend randomized, controlled trials of high and low fiber diets.
April 21, 2006
High magnesium linked with reduced mortality over an eighteen year period
The findings of a study published in the May 2006 issue of the journal Epidemiology revealed an association between having high serum levels of magnesium and a lower risk of mortality during an eighteen year follow-up. The study also found an increase in mortality linked with high serum copper levels.
Researchers at the National Institute of Health and Medical Research in France evaluated data from the Paris Prospective Study 2, which included 4,035 Parisian men between the ages of 30 and 60. Blood samples drawn upon enrollment were analyzed for serum zinc, copper and magnesium levels, and other factors.
During the follow-up period there were 176 cancer deaths, 56 cardiovascular disease deaths, and 107 deaths from other causes, including homicide and digestive disorders. Individuals whose serum magnesium levels were in the top one-fourth of participants had a 40 percent lower risk of dying from any cause or from cardiovascular disease, and a 50 percent lower risk of dying from cancer during follow-up than those whose magnesium was in the lowest fourth. Conversely, having high copper levels increased the risk of dying by 50 percent when the top 25 percent and lowest 25 percent of serum values were compared.
The results support those of other surveys that have determined increases in cancer and heart disease mortality associated with elevated serum copper, decreased cancer mortality associated with zinc, and reduced all-cause mortality associated with higher levels of magnesium. The authors explain that zinc deficiency is associated with depressed immune function and that copper is involved in oxidative damage. Reduced levels of magnesium are may be associated with an increase in low density lipoprotein oxidation and could initiate inflammation. Additionally magnesium and zinc help stabilize DNA, which could help prevent in the initiation of cancer.
April 19, 2006
Mediterranean diet linked with Alzheimer's disease reduction
In an article published online in advance of print in the Annals of Neurology researchers funded in part by the National Institutes on Aging reported an association between consuming a Mediterranean diet and having a lower risk of developing Alzheimer's disease. The Mediterranean diet contains high amounts of fruits, vegetables, legumes and grains, some fish and alcohol, and less meat and dairy products. Recent research has revealed a lower risk of cardiovascular disease and certain cancers associated with this pattern of eating.
Nikolaos Scarmeas of Columbia University Medical Center and his New York team conducted the current study of 2,258 men and women enrolled in the Washington Heights-Inward Columbia Aging project. Participants were free of dementia at the beginning of the study, and were followed for an average of four years. Medical and neurological histories were obtained, and physical and neurological examinations were conducted at the beginning of the study and every 18 months to determine whether dementia had developed. Dietary questionnaires completed by the participants were evaluated to determined how closely the subjects followed a Mediterranean diet, and participants were scored from 0 to 9 according to their adherence.
Two hundred sixty-two subjects were diagnosed with Alzheimer's disease over the follow-up period. Subjects whose diet adherence scores were among the top third of participants had a 40 percent lower risk of developing Alzheimer's disease than those in the lowest third, while those whose scores fell in the middle third experienced a 15 percent lower risk. The response to the diet appeared to be dose-dependent, with each Mediterranean diet score point associated with a reduction in Alzheimer's disease risk of 9 to 10 percent.
"We conclude that higher adherence to the Mediterranean diet is associated with a reduction in risk for Alzheimer's disease," the authors write.
April 17, 2006
Vitamin D supplements suppress inflammation in congestive heart failure patients
A report published in the April, 2006 American Journal of Clinical Nutrition revealed that supplementing congestive heart failure patients with vitamin D lowered cytokines that contribute to inflammation while elevating those that suppress it. Congestive heart failure, a condition in which inflammation plays a role, occurs when the heart fails to pump blood efficiently, and can be caused by hypertension, cardiomyopathy, diabetes, coronary artery disease or defective heart valves.
Researchers in Germany gave 123 congestive heart failure patients 50 micrograms vitamin D3 (equivalent to 2,000 international units) with 500 milligrams calcium per day, or a placebo plus 500 milligrams calcium for nine months. Blood serum was evaluated for 25-hydroxyvitamin D, parathyroid hormone, the pro-inflammatory cytokine tumor necrosis factor alpha and the anti-inflammatory cytokine interleukin 10.
Of the ninety-three participants who completed the study, those who received vitamin D experienced an increase in 25-hydroxyvitamin D levels and the anti-inflammatory cytokine interleukin 10, while parathyroid hormone levels decreased. The pro-inflammatory cytokine tumor necrosis factor alpha remained stable in this group, while increasing among those who received the placebo. Survival rates were similar for both groups.
The authors conclude, "Vitamin D3 reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease."
In an accompanying editorial, Reinhold Vieth and Samantha Kimball of the University of Toronto observed that the article is important because it confirms that vitamin D supplementation affects immune modulating cytokines beneficially, and that it points to a higher dose of the vitamin to achieve this. They remark that a previous study which used 400 IU per day failed to affect cytokine levels. "A conventional diet alone cannot ensure adequate concentrations of vitamin D, which means that supplements are often necessary," they note.
April 14, 2006
Another cancer inhibited by chili pepper compound
In addition to the recently reported inhibitory effect of the red chili pepper ingredient capsaicin on prostate cancer cell growth, the compound has now been found to reduce the growth of pancreatic cancer cells. Pancreatic cancer is the fifth leading cause of cancer death in the United States, and one of the most aggressive types of the disease. The findings were presented during the Late Breaking Session at the annual meeting of the American Association for Cancer Research, held April 1 to 5 at the Washington Convention Center in Washington, D.C.
Sanjay K. Srivastava, PhD, who is an assistant professor at the University of Pittsburgh School of Medicine's department of pharmacology, and his colleagues grafted pancreatic tumors into mice and fed them varying concentrations of capsaicin three or five days per week. A control group of mice received normal saline minus the compound. The team found that animals who received capsaicin had higher levels of apoptosis-associated proteins, and tumors that were half the size of those in the control group. It was discovered that capsaicin disrupted the cancer cells' mitochondria--the energy producing organelle's of the cell--which caused the release of apoptotic proteins.
"In our study, we discovered that capsaicin fed orally to mice with human pancreatic tumors was an extremely effective inhibitor of the cancer process, inducing apoptosis in cancer cells," Dr Srivastava summarized. "Capsaicin triggered the cancerous cells to die off and significantly reduced the size of the tumors."
"Our results demonstrate that capsaicin is a potent anticancer agent, induces apoptosis in cancer cells and produces no significant damage to normal pancreatic cells, indicating its potential use as a novel agent for the prevention and treatment of pancreatic cancer," he concluded.
April 12, 2006
Analysis finds inverse relationship between serum vitamin D levels and breast cancer risk
The results of a pooled analysis of 1,760 women confirmed that having higher levels of the vitamin D metabolite serum 25-hydroxyvitamin D is associated with a lower risk of breast cancer. The finding was reported at the 97th Annual Meeting of the American Association for Cancer Research held April 1-5, 2006 in Washington DC.
Cedric Garland, Dr PH, and Edward Gorham, PhD, of the University of California, San Diego, and their colleagues evaluated data from cancer studies conducted by Elizabeth R. Bertone-Johnson and colleagues at Harvard, and L.C. Lowe and associates at Saint George’s Hospital Medical School in London to arrive at their conclusion. "There is a strong inverse dose-response relationship between the serum concentration of 25-hydroxyvitamin D and the risk of breast cancer," Dr Garland stated. "It's a close fit to a linear model."
The research team found that having a serum vitamin D level of 52 nanograms per milliliter was associated with a 50 percent reduction in breast cancer risk. To attain this level of the vitamin, it would be necessary to consume at least 1,000 international units (IU) of vitamin D per day--more than three times as much as most Americans receive. Although the National Academy of Sciences has established 2,400 IU per day as the upper limit for vitamin D intake, there have been no toxic effects associated with up to 3,800 IU per day. "There is no substantial downside to a serum level of 52 nanograms per milliliter of Vitamin D," Dr Gorham noted. "Such levels are common in sunny climates. There is no known adverse effect of serum levels below 160 nanograms per milliliter."
The researchers recommend that at least 1,000 IU per day vitamin D3 be consumed until further studies are conducted.
April 10, 2006
Cruciferous vegetables halt prostate cancer growth in mice
The annual meeting of the American Association for Cancer Research held in Washington, DC, was the site of a presentation on April 5, 2006 by Shivendra Singh, PhD of the University of Pittsburgh School of Medicine of the discovery that compounds found in cruciferous vegetables are able to arrest the growth of human prostate cancer tumors implanted into mice. Cruciferous vegetables are a family of vegetables that include broccoli, watercress, cabbage and cauliflower, and have been associated with cancer preventive benefits in a number of studies.
The University of Pittsburgh Cancer Institute researchers grafted human prostate tumor tissue into mice, followed by the oral administration of a small quantity of phenethyl-ITC (PEITC), a type of isothiocyanate that is generated in cruciferous vegetables when they are cut or chewed. The amount of the compound given to the animals was equivalent to concentrations achievable human diets.
After 31 days of treatment, the team found that PEITC induced apoptosis, or programmed cell death, in cancerous cells. Mice in whom tumors were implanted who did not receive the compound had an average tumor volume that was 1.9 times greater than those who received PEITC.
Dr Singh commented, "The contribution of diet and nutrition to cancer risk, prevention and treatment have been a major focus of research in recent years because certain nutrients in vegetables and dietary agents appear to protect the body against diseases such as cancer. From epidemiologic data, we know that increased consumption of vegetables reduces the risk for certain types of cancer, but now we are beginning to understand the mechanisms by which certain edible vegetables like broccoli help our bodies fight cancer and other diseases. Our next step is to design clinical trials to determine the efficacy of PEITC for prostate cancer prevention in men."
April 7, 2006
Omega-3 fatty acid involved in eye retina protection
In an article published online on April 3 2006 in the journal Trends in Neuroscience, Nicolas G. Bazan, MD, PhD, describes his discovery of a protective role for the omega-3- fatty acid docosahexaenoic acid (DHA) against degenerative diseases of the retina. In these diseases, which include age-related macular degeneration and retinitis pigmentosa, photoreceptor cells degenerate and die, leading to vision loss.
Dr Bazan, who is the Director of the Neuroscience Center of Excellence at Louisiana State University Health Sciences Center in New Orleans, in collaboration with researchers at Harvard University, found that DHA in retinal pigment epithelial cells is a precursor to a compound called neuroprotectin D1, which is synthesized by the cells as part of a response to oxidative stress, sunlight, or trauma. Retinal pigment epithelial cells are responsible for maintaining the photoreceptor cells that degenerate in retinal diseases, as well as regulating the delivery of DHA to these cells. Neuroprotectin D1 prevents genes which cause inflammation and cell death from being switched on by oxidative stress and other factors, consequently promoting the survival of the retinal pigment epithelial cells. The compound as well as its precursor DHA also reduce free radical production. In addition, DHA facilitates the expression of proteins that promote protective cell signaling.
Dr Bazan has found that DHA also promotes survival and inhibits cell death in neurons in a model of Alzheimer's disease.
"Because the early clinical manifestations of most retinal degeneration precedes massive photoreceptor cell death, it is important to define the initial crucial events," Dr. Bazan observed. "This knowledge might be applicable to the design of novel therapeutic interventions to halt or slow disease progression."
April 5, 2006
Ginger induces death in ovarian cancer cells
A poster session presentation at the American Association for Cancer Research's 97th annual meeting, held April 1-5, 2006 in Washington, DC, revealed the finding of researchers from the University of Michigan Comprehensive Cancer that ginger caused the death of cultured ovarian cancer cells by two separate mechanisms in all of the cell lines tested. It is suspected that ginger's anti-inflammatory action is responsible for its ability to inhibit cancer cell growth.
By applying standard research grade powdered ginger dissolved in solution to ovarian cell cultures, assistant professor of obstetrics and gynecology J. Rebecca Liu, MD, and her University of Michigan School of Medicine colleagues found that ginger induced cell death through the process of programmed cell suicide known as apoptosis, as well as by autophagy, during which cells digest or attack themselves. Coauthor Jennifer Rhode, MD, who is a gynecologic oncology fellow at the University of Michigan Medical School, stated, "In multiple ovarian cancer cell lines, we found that ginger induced cell death at a similar or better rate than the platinum-based chemotherapy drugs typically used to treat ovarian cancer."
"Most ovarian cancer patients develop recurrent disease that eventually becomes resistant to standard chemotherapy – which is associated with resistance to apoptosis," Dr Liu commented. "If ginger can cause autophagic cell death in addition to apoptosis, it may circumvent resistance to conventional chemotherapy."
Dr Liu's team is also investigating the effects of two other natural substances on ovarian cancer: resveratrol and curcumin, as well as researching the effects of ginger in colon cancer and chemotherapy-induced nausea. They plan to test ginger's effect against ovarian cancer in animal studies.
April 3, 2006
Liver cancer cell growth prevented by omega-3 fatty acids
The results of two studies presented on April 3, 2006 at the American Association for Cancer Research's annual meeting revealed that the omega-3 fatty acids eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit the growth of liver cancer cells in culture.
Tong Wu, MD, PhD, who is a member of the division of transplantation pathology at the University of Pittsburgh School of Medicine, and whose laboratory was used to conduct the research explained, "It has been known for some time that omega-3 fatty acids can inhibit certain cancer cells. So, we were interested in determining whether these substances could inhibit liver cancer cells. If so, we also wanted to know by what mechanism this inhibition occurs."
The research team examined the effect of DHA and EPA and the omega-6 fatty acid arachidonic acid in human hepatoceullar cancer cells, a common type of liver cancer. After treating the cells for 12 to 24 hours, they found an inhibition of cell growth dose-dependently associated with EPA and DHA, while arachidonic acid failed to have an effect. They believe that the effect observed in this study was due to apoptosis, or programmed self-destruction, of the cancer cells. In addition, DHA and EPA indirectly reduced levels of the protein beta-catenin, which, when elevated, has been linked to the development of some tumors.
A second experiment looked at the effect of omega-3 and omega-6 fatty acids in cholangiocarcinoma cells, which is an agressive form of liver cancer, and discovered a similar ability of omega-3 fatty acids to inhibit cell growth and lower beta-catenin.
"Our finding that omega-3 fatty acids can decrease levels of beta-catenin is further evidence that these compounds have the ability to interact on several points of pathways involved in tumor progression," Dr Wu concluded.