Vitamin C deficient mice have vulnerable plaque
The March 26 2002 issue of Circulation: Journal of the American Heart Association published the results of a study demonstrating that chronic vitamin C deficiency, while not effecting the initiation or progression of atherosclerotic plaques, produces a type of plaque that is vulnerable to rupture, leading to cardiac events. The plaque produced by the deficient rats contained lower amounts of collagen and larger necrotic cores. These mice also showed less fibroproliferation and neovascularization in the outer layer of the aorta, the large vessel that carries blood away from the heart.
Mice bred to be dependent upon dietary vitamin C due to the lack of an enzyme and to be susceptible to atherosclerosis due to the absence of apolipoprotein E, were given regular diets or high fat Western-type diets. The mice receiving the normal diet were given approximately 1, 2.5 or 17 milligrams vitamin C per day, and mice receiving the high fat diets received 0.37 milligram, 1 milligram or 17 milligrams of the vitamin per day. Postmortem examination of the mice revealed collagen fibers forming intricate networks throughout the plaque in mice receiving high levels of vitamin C in both dietary groups, which were less marked in those who received low levels, predisposing these plaques to weakness and rupture. The mice receiving low amounts of vitamin C had minimal thickening of the outer layer of the aorta, and less formation of new blood vessels compared to the high vitamin C group. This reduced neovascularization may limit the supply of oxygen and nutrients to the plaques, promoting necrosis.
In humans, heart disease symptoms develop when plaques become unstable. The features of the plaques found in vitamin C deficient mice were similar to those in humans with high-risk plaques vulnerable to rupture.
Vitamin C is important in wound healing because of its necessity for the formation of collagen. As plaques form at the site of injury within blood vessels, higher levels of vitamin C may be necessary to help increase collagen, improving plaque stability.
Lower drug costs could add years to life
The April 2002 issue of the American Journal of Preventive Medicine published a review of studies examining the cost and health effects of the use of pharmaceuticals by older individuals. Researchers at Rutgers University analyzed five studies published between 1990 and 2000, including three on the use of statins to reduce cholesterol, in order to determine how many years of life would be added for each one million dollars spent if the drugs were sold at the average wholesale price, and 20% or 40% below the average wholesale price. Individuals lacking prescription drug insurance pay the highest prices for their medications, whereas federal purchases pay 40 to 50 percent below the average wholesale price, and managed care prices lie somewhere between the two.
The researchers' analysis revealed that on average, older individuals with a history of heart attack could experience double the extension of life statins are capable of producing if their costs were lowered by 40%.
Louise B Russell PhD and Nancy Wolff PhD, of Rutger's Institute for Health, Health Care Policy and Aging Research write, "Much of the discussion regarding the addition of a prescription drug benefit to Medicare has centered on issues of cost -- budgetary cost to Medicare and out-of-pocket costs to the elderly. Important and easily measured, costs have overshadowed the health consequences of the benefit. A Medicare drug benefit program that supports prices at the high end of the current range could yield substantially less health for the elderly . . . It is important to evaluate drug benefit proposals in terms of health effects per dollar, not just dollars."
Calcium plus vitamin D can reverse bone loss occurring in high protein diets
In the results of a study to appear in the April 2002 American Journal of Clinical Nutrition, researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University demonstrated that adequate calcium and vitamin D can reverse bone loss that can occur with high protein diets. Three hundred forty-two healthy men and women over the age of sixty-five were randomized to receive 500 milligrams calcium per day along with vitamin D or a placebo for a period of three years, and diets and bone mass density were assessed. Protein intake for the participants ranged from 79 to 96 grams per day, well above the recommended protein intake for healthy people of 40 to 60 grams per day. A high protein diet may benefit older individuals in preventing muscle wasting and promoting wound healing.
The group receiving calcium experienced an increase in bone mass density, whereas the placebo group experienced a reduction in calcium levels with rising protein intake. Protein source did not effect bone density. The researchers explained that sufficient calcium intake may be conducive to protein aiding calcium absorption.
Lead author and senior scientist and chief of the Calcium and Bone Metabolism Laboratory at the Human Nutrition Research Center on Aging, Bess Dawson-Hughes, MD summarized, "Our results suggest that a higher calcium intake is going to be protective against any adverse effects of protein on bone, and may allow protein to have a positive effect. These results help us to better understand the mechanics behind calcium and vitamin D supplementation and their effect on bone mass density. This study is a significant confirmation that adequate calcium in the diet is crucial. This report, however, also shows that there is much more research needed in this area."
Adequate vitamin B6 improves transplant survival
Researchers at the Cleveland Clinic in Cleveland, Ohio and at Wake Forest University in Winston-Salem North Carolina sought to determine the relationship between the elevated homocysteine levels and low levels of folate and vitamin B6 observed in heart transplant patients, and the risk of complications or death following the surgery. In a study partly funded by the National Institutes of Health, 160 patients were enrolled who had undergone heart transplants due to idiopathic dilated cardiomyopathy, coronary artery disease, valvular heart disease, restrictive cardiomyopathy, congenital heart disease or other indications. Fasting plasma homocysteine, cholesterol LDL, creatinine and glucose levels; as well as folic acid, vitamin B12 and plasma pyridoxal 5'-phosphate (the active form of vitamin B), were measured and patients were followed for an average of five years subsequent to their procedures.
Although elevated serum homocysteine levels was found in the majority of the participants, it did not predict cardiovascular complications or death, with survival being equal in those with high and low homocysteine. Pyridoxal 5'-phosphate, or vitamin B6 levels were observed in 21% of the subjects in who complications or death occurred, and in 9% of those in whom complications or death did not occur. The survival of individuals with a deficiency in the B vitamin was significantly lower than that of those who had adequate levels of the vitamin. Elevations in serum creatinine also increased the risk of complications and death, a finding that was independent of one another.
Vitamin B6 may be involved in several thrombotic processes including cholesterol metabolism, clotting factor activity and platelet function, rendering the vitamin important in the prevention of cardiovascular complications independent of its relationship to homocysteine.
Magnesium deficiency causes arrhythmias in women
The March 2002 issue of the American Journal of Clinical Nutrition, http://www.ajcn.org/ published a study of twenty-two women which showed that magnesium deficient diets increased supraventricular ectopy, a type of heart arrhythmia. The women, aged 47 to 78, received diets containing less than half the US recommended dietary allowance for magnesium. Subjects were maintained in a metabolic unit and were supervised for six months. For the initial eighty-one days of the study, participants were randomized to receive either a placebo or a magnesium gluconate supplement that would raise their magnesium level to greater than the RDA of 320 milligrams per day. Following this period, subjects were switched to the opposite regimen. One or three milligrams copper was supplemented throughout the course of the study to compensate for the copper deficiency that accompanies magnesium deficient diets.
The low magnesium regimen was determined to provide 130 milligrams magnesium per day, while the high magnesium diet provided 411 milligrams. Magnesium deficient diets predictably lowered serum, urinary and erythrocyte magnesium. Ionized plasma magnesium levels were not affected. Heart rhythms were monitored via Holter electrocardiograms. Supraventricular beats as well as supraventricular plus ventricular beats were significantly higher when the subjects were not consuming adequate magnesium.
Because magnesium is central to many cellular mechanisms controlling muscle and nerve cell activity, a deficiency may result in heartbeat abnormalities. Less than half of the RDA consumed for an eighty-one day period changed heart rhythm in this study. A magnesium deficient diet is not likely to benefit individuals with valvular disease or cardiac hypertrophy, or consumers of alcohol or caffeine who are predisposed to cardiac arrhythmia, and these individuals may require more magnesium than an average diet provides.
Soy may help individuals faced with chronic pain
Chronic pain effects over two-thirds of advanced cancer patients. Opioid drugs such as morphine are currently the most effective weapons against pain, but side effects which include constipation and nausea render their use unacceptable by many patients.
The results of a study funded by the National Center for Complementary and Alternative Medicine, presented on March 15 at the annual meeting of the American Pain Society held in Baltimore showed that rats consuming diets high in soy experienced a greater tolerance to pain and less inflammation when exposed to heat stimuli. The Johns Hopkins researchers, led by Jill M Tall PhD, fed one group of ten rats a milk protein based diet and another group a soy protein based diet for two weeks. The rats randomly received an injection in their hind paw of a placebo or a substance that produced inflammatory pain. Paw thickness was measured to determine fluid build-up and pain and pressure tolerance assessed prior to injection and at six, twenty-four, forty-eight and ninety-six hours following the injection. The animals who were fed the soy-based diet experienced significantly less swelling and a greater tolerance to pain than those fed the milk protein based diets. Reaction to pressure stimuli did not appear to be effected by either dietary regimen.
The results of this study concurred with an earlier study demonstrating that soy based diets suppressed pain after nerve injury.
Dr Tall commented, "Our generation is very open to the idea of dietary methods of pain control. We hope to find complementary and alternative treatments to help people suffering from pain."
Mayo Clinic shows NSAIDs may help prevent prostate cancer
The March 2002 issue of Mayo Clinic Proceedings published the results of a population-based study revealing that men age 60 and older who were regular users of nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen reduce their risk of prostate cancer by up to 60 percent. The protective effect may increase as one ages, suggesting that the drugs may prevent the progression of the disease from latent to clinical disease.
The study followed 1,362 Caucasian men ages 50 to 79 for an average of five and one half years. Seven hundred ninety-three participants were nonusers of nonsteroidal anti-inflammatories, while 569 reported daily use of the drugs. During follow up, 8.6% of those who did not use the drugs were diagnosed with prostate cancer, compared to only 4% of those who used NSAIDs. The preventive benefits of the drugs appeared to increase with age, with those age 70 and older experiencing the greatest risk reduction.
Lead researcher and Mayo Clinic epidemiologist Rosebud Roberts, MD commented, "These numbers mean the proportion of men who used NSAIDs daily and developed prostate cancer was about one-half that of men who did not use NSAIDs daily -- four percent compared to nine percent. Further, the association between NSAIDs and prostate cancer appears to be stronger in older men. The risk of prostate cancer among NSAID users was 12 percent lower in men age 50 to 59 years, 60 percent lower in men 60 to 69 years, and 83 percent lower in men age 70 to 79 years compared to men in those same age groups who did not use NSAIDs daily... While our findings complement previous studies that NSAIDs help protect against breast and colon cancers, and possibly against prostate cancer, there are also negative side effects of NSAIDs that need to be considered and monitored in people who take NSAIDs on a daily basis."
Green tea extracts protect cartilage
A study conducted at the University of Sheffield Medical School, in Sheffield, England, and reported in the March 2002 issue of the Journal of Nutrition, investigated the effect of green tea catechins on human and bovine cartilage cultures. Although these polyphenols have been previously demonstrated to alleviate inflammation in mice, it had been unknown whether they protected the joints.
Green tea catechins were added to bovine nasal and joint cartilage cultures as well as three cultures of human cartilage that had been removed during joint replacement or other surgery which provided osteoarthritic, rheumatoid and macroscopically normal human cartilage. The researchers sought to determine the amount of proteoglycan degradation as well as type II collagen breakdown, induced by exposure of the cultures to several proinflammatory substances.
The green tea catechin epigallocatechin gallate (EGCG) prevented tumor necrosis factor-stimulated proteoglycan degradation in the bovine nasal cartilage culture, while the catechins epicatechin gallate (ECG) and epicatechin (EC) inhibited interleukin 1-alpha stimulated degradation. In the bovine joint cartilage culture, EGCG prevented proteoglycan breakdown when challenged with several inflammatory substances, as did ECG. In human cartilage, ECG significantly inhibited proteoglycan breakdown in osteoarthritic, rheumatoid and nonaffected cartilage treated with interleukin 1-beta and tumor necrosis factor. EGCG, ECG and epigallocatechin (EGC) reduced the degradation of type II collagen in bovine nasal cartilage when treated with interleukin 1-alpha.
The catechins' benefits may be due to both their antiinflammatory properties as well as an antiproteolytic effect which protects the cartilage. It remains to be demonstrated whether oral administration of green tea catechins can elevate levels in the joints sufficiently to prevent cartilage breakdown.
Ensuring sufficient dietary magnesium prevents cardiovascular disease in diabetics
Researchers at Odense University Hospital in Odense, Denmark, and the State University of New York Health Science Center in Brooklyn have confirmed that the increase in cardiovascular disease caused by magnesium deficiency in diabetics is due to their diets containing less than adequate amounts of the mineral, and that longterm supplementation with magnesium can reduce this increased risk.
The research, published in the December 2001 issue of the journal Metabolism: Clinical & Experimental, tested the hypothesis by supplementing magnesium in ten type 1 diabetic patients and five control patients who did not have diabetes. Test subjects had their daily magnesium intakes calculated before initiating supplementation and were tested for serum cholesterol, serum low-density lipoprotein and apolipoprotein B. Participants received oral magnesium oxide supplements for twenty-four weeks, after which they were retested.
Eighty percent of the diabetic patients had a magnesium intake of lower than 90% of the recommended daily allowance at baseline as well as a muscle magnesium content that was decreased by 7%. After twenty-four weeks, magnesium supplementation elevated muscle magnesium by 5% while lowering serum total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B. The participants also experienced a 35% decline in insulin-stimulated glucose uptake.
The researchers concluded that the diets of type 1 diabetics are magnesium deficient and that supplementing this mineral will decrease atherogenic lipid fractions and lower blood sugar.
Gene found to control brain aging
Researchers at Duke University in Durham, North Carolina, have discovered a genetic link between a variation in the apolipoprotein gene, designated APOE4, and the development of age-related changes in the brain. The findings were presented at the fifteenth annual meeting of the American Association for Geriatric Psychiatry held in February of this year.
The APOE4 variant is carried by approximately one quarter of the population. Research has established that carriers have a greater risk of Alzheimer's disease, heart disease, and memory loss after head injury or bypass surgery. The researchers measured the levels of a chemical known to be closely associated with nerve cells and mental functions known as N-acetyl aspartate, or NAA, in 165 healthy individuals ages 55 through 85, through the use of magnetic resonance spectroscopy. Study participants were grouped according to whether they possessed the APOE4 variant and given tests to assess cognitive function. When the tests were repeated after two years, it was found that subjects with the lowest NAA levels at the study's onset experienced a greater loss of short term memory and naming ability than those whose NAA levels were higher.
Research team leader and Duke University psychiatrist P Murali Dorasiwamy, MD, elaborated: "We found that NAA levels declined mildly with increasing age for all participants in the study. But when the sample was broken down by genetic makeup, the average loss of NAA across the age span was nearly three-fold higher in people with the APOE4 gene than in those who were not carriers of this gene... This is an important finding in the study of aging. I believe it will lead to a greater understanding of age-related memory loss and hopefully, one day, to ways of keeping our brains sharper, longer."
Low methylfolate status associated with venous thromboembolism
A study reported in the March 2, 2002 issue of The Lancet showed a correlation between the risk of venous thromboembolism and low levels of folate and methylfolate in red blood cells. It has been known that elevated levels of homocysteine are a risk factor for venous thromboembolism but it had not been known if the risk was caused by homocysteine or components of the homocysteine remethylation pathway. Methylfolate is one component of that pathway, necessary for the conversion of homocysteine to methionine, and dependent upon the body's folate, or folic acid, status. Vitamin B12 is also a cofactor in this process.
In a multicenter case-controlled study, 243 patients diagnosed with deep vein thrombosis and/or pulmonary embolism were matched with controls who did not have venous thromboses. Blood samples were taken to measure homocysteine, methionine, plasma folate, total folate and methylfolate in red blood cells, and other risk factor for the condition.
Univariate analysis showed elevated homocysteine, and low methionine, plasma folate, and total folate and methylfolate in red blood cells as significant risk factors. While weakening other associations, multivariate analysis showed methylfolate in red blood cells remaining as a strong risk factor. Individuals having the lowest levels of methylfolate experienced seven times the risk of venous thrombosis than did those whose levels were the highest. This points to a disequilibrium of the homocysteine remethylation cycle in patients with the condition. The researchers concluded that the concentration of folates, in particular methylfolates, within red blood cells are a strong risk factor for venous thromboembolism, independent of homocysteine and other factors.
Resveratrol's anticancer mechanism defined
Researchers at De Montfort University in Leicester, England, have discovered the mechanism of action of resveratrol against cancer. Resveratrol, a substance found in grapes, had been previously demonstrated to have cancer-fighting properties, but how it is able to do so has heretofore been unknown. The researchers discovered that resveratrol is converted in the body by the cytochrome P450 enzyme CYP1B1, found on a variety of tumors, to a substance called piceatannol, a tyrosine kinase inhibitor which is toxic to cancer cells. The process is restricted to the tumor, preventing toxicity to healthy cells.
Resveratrol is naturally produced in plants such as peanuts and grapes to aid them in combating fungus. It was previously believed that the enzyme CYP1B1 was involved in initiating cancer, because it is found only in tumors. The study provides additional insight into CYP1B1's role as a growth suppressor enzyme.
Research team leader and coauthor Professor Gerry Potter, of De Montfort University's School of Pharmacy commented, "The belief that CYP1B1 is a cause of cancer is like blaming police for a crime just because they are on the scene. We suspected that resveratrol might be beneficial for health and have cancer preventative properties. This research shows just how it could prevent tumours developing by producing these anticancer molecules within the cancer cells themselves . . . Learning from nature in this way will help in our work to design drugs which are selectively activated in a tumour and can form the basis of anticancer treatments."
The report appears in the March 4 2002 issue of British Journal of Cancer.