C-reactive protein directly involved in inflammation
C-reactive protein (CRP) is a plasma marker of inflammation that, when elevated, has been found to be a risk factor for atherosclerosis. However, evidence that this protein is plays a causative role in the development of heart disease has been limited. A study published online in the American Heart Association journal, Circulation, on January 26, 2004 has found for the first time in an animal model that C-reactive protein not only predicts the presence of atherosclerosis, but is involved in its development. Atherosclerosis is characterized by the buildup of fatty plaques in the arteries, which causes them to narrow and can lead to heart attack or stroke.
Working with mice bred to develop atherosclerosis in addition to expressing a human form of C-reactive protein, researchers from Baylor College found that atherosclerotic plaques these mice were larger than those in atherosclerotic mice who were not bred to express CRP. The research team, led by Baylor College of Medicine's diabetes, endocrinology and metabolism division chief, Dr Lawrence Chan, found high levels of the arterial wall cell surface protein known as angiotensin type 1 receptor in the plaques of the mice expressing CRP, and lower levels in the mice who did not express CRP. High levels of this receptor render cells more susceptible to inflammation. The angiotensin receptor blocking drugs used by some heart patients may be particularly effective in those with elevated CRP levels. There was no blood pressure difference between the two groups of mice, indicating that the atherosclerosis-promoting effect of CRP via angiotensin type 1 receptor was not brought about by the receptor's hypertensive property.
Dr Chan summarized, "Our study supports the use of C-reactive protein as a marker of risk for heart disease. Not only that, but it identifies at least one mechanism by which the protein contributes to the development of atherosclerosis."
Vitamin D supplements recommended for burn victims
A letter published in the January 24 2004 issue of The Lancet recommends supplementation with vitamin D following acute burn injuries. The letter, coauthored by vitamin D researcher Michael F Holick, summarized a study that included 12 children who with burn injuries averaging 52 percent of their body surface. Biopsy samples were taken from scar tissue and adjacent areas over a year after their injuries and levels of levels of the vitamin D3 precursors 7-dehydrocholesterol, and its conversion product previtamin D3 were determined. Tissue samples taken from nonburned wound site skin of healthy volunteers and from newborn foreskins following circumcision were used as control samples.
An average of fourteen months following their injuries, 73 percent of the burn patients were found to have deficient blood levels of 25-hydroxyvitamin-D, the form of the vitamin that is the main criterion for determining vitamin D deficiency. When the scar tissue samples were examined, 7-dehydrocholesterol was lower in the burn patients compared to the controls. Previtamin D3 in both scar tissue and adjacent skin was significantly lower in burn patients compared to controls.
Previous research revealed an association between acute burn injury in childhood and subsequent low lumbar spine bone mineral density, indicating longlasting bone loss. Deficient levels of serum vitamin D have also been noted in these patients. Because vitamin D is involved in maintaining bone mass, a defect in the ability of the burned skin to produce this vitamin may be responsible for these findings. Additionally, the reduced ability of skin adjacent to scar tissue to synthesize vitamin D shows that this phenomenon occurs in a total body surface area greater than that involved in the burn. The authors postulate that “scar tissue has more ultraviolet-B-absorbing substances similar to melanin and sunscreens,” and they conclude that, “burn patients should receive vitamin D supplementation.”
Increased vitamin D intake associated with reduced rheumatoid arthritis
Data obtained from the Iowa women's Health Study has yielded the promising finding that vitamin D from both diet and supplements is inversely associated with the risk of rheumatoid arthritis. The Iowa Women's Health Study is a population-based study begun in 1986 which included 41,836 between the ages of 55 and 69. The current study analyzed 29,368 participants who did not have rheumatoid arthritis at the study's onset.
Food frequency questionnaires administered in 1986 were analyzed to determine vitamin D and calcium intake. Over the eleven year followup period, 152 cases of rheumatoid arthritis were identified. Total vitamin D intake, vitamin D from diet and vitamin D from supplements were all negatively associated with rheumatoid arthritis. Supplemental vitamin D was more strongly associated with an adverse relationship to rheumatoid arthritis risk than vitamin D from diet. Total calcium intake from all sources was not found to be associated with rheumatoid arthritis risk.
Rheumatoid arthritis is an autoimmune disease whose cause is unknown, although genetic and nongenetic factors have been identified to play a role in susceptibility to the disease. The authors of the study acknowledge that vitamin D has an immunologic activity apart from its role in calcium regulation, and has been shown to have an immunosuppressant effect in laboratory studies, possibly explaining its mechanism of action in rheumatoid arthritis. The findings in this study may have relevance to other immunologic disorders, creating the need for further research.
The study was published in the January 2004 issue of the journal Arthritis & Rheumatism.
Low magnesium predicts neurologic events in atherosclerotic patients
A study published in the January 2004 issue of the American Heart Association journal, Stroke, found that a deficiency in the essential mineral magnesium is associated with an increased incidence of neurologic events including stroke in individuals with peripheral artery disease who are at high risk for complications of atherosclerosis.
Researchers in Vienna, Austria followed 323 men and women with peripheral artery disease and intermittent claudication for a median of twenty months to determine the incidence of ischemic stroke and/or carotid revascularization (endarterectomy or stenting of the carotid artery). Serum magnesium levels were ascertained at the study's onset. The aforementioned neurologic events occurred in 11 percent of the subjects, with stroke occurring in fifteen participants, carotid revascularization occurring in thirteen and stroke with subsequent revascularization occurring in seven.
It was found that subjects whose serum magnesium levels were in the lowest one-third of the study population (defined as less than 0.76 micromoles magnesium per liter) experienced a greater than three-fold increased risk for neurologic events compared to those in the top third, while those whose magnesium levels were in the middle third did not experience an increased risk. Magnesium levels were not found to be associated with all-cause mortality or coronary events.
Epidemiological studies have revealed an association between magnesium deficiency and atherosclerosis. The findings from other studies suggest that dietary magnesium may help lower blood pressure and subsequently reduce the risk of stroke. The authors of the current study concluded that low serum magnesium levels are a risk factor for neurologic events in symptomatic peripheral artery disease patients and recommend, “ magnesium substitution therapy in those patients with advanced atherosclerosis.”
Melatonin: high blood pressure remedy of the future?
The January 19 2004 rapid access issue of Hypertension: Journal of the American Heart Association , published the results of a study conducted at the Netherlands Institute for Brain Research in Amsterdam, which found that hypertensive men taking the hormone melatonin experienced reduced nighttime blood pressure. Melatonin is a hormone involved in circadian rhythms produced by the pineal gland in the brain, and is taken as a safe over the counter sleep remedy by numerous individuals.
Sixteen men with untreated essential hypertension were administered 2.5 milligrams melatonin or a placebo one hour before sleep for three weeks, and the results were compared to those obtained when melatonin was given for one day only. In those who received the longer melatonin treatment, ystolic blood pressure dropped by 6 millimeters of mercury and diastolic blood pressure was reduced by 4 millimeters Melatonin given in one single dose only had no effect on blood pressure. Additionally, the group who received melatonin reported an improvement in sleep.
Lead author Frank A.J.L. Scheer , PhD, who is a neuroscientist at Brigham and Women's Hospital in Boston and at Harvard Medical School's division of sleep medicine, commented, "It has been reported that people with high blood pressure often have suppressed nighttime melatonin levels. We have recently found that people with high blood pressure have actual anatomical disturbances of their biological clocks. This finding might open the door for a new approach for treating hypertension.” He added, “This is just a start. Large-scale studies need to be done, as well as studies of potential interactions between melatonin and traditional antihypertensive treatments."
Prevention of “normal” brain aging
An American Medical Association media briefing in New York on January 15, 2004 was the site of a presentation by Alzheimer's Association Medical and Scientific Advisory Committee chair Marilyn Albert, PhD, on the prevention of so called “normal” brain aging as opposed to Alzheimer's disease (AD).
Dr Albert explained the difference between developing Alzheimer's disease, and the decline in cognitive function that occurs in aging individuals who do not have the disease. While neurons are lost in Alzheimer's disease, memory loss associated with normal aging is likely to be the result of changes in the way neurons communicate. Pharmaceutical agents that are used prevent and treat Alzheimer's disease may have side effects that render them inappropriate for healthy people. Nevertheless, understanding how to maintain normal brain health is providing clues about what may reduce the likelihood of developing Alzheimer's disease. The National Institute on Aging, National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke are collaborating to unify the knowledge that has been gained on the subject, and to find ways of extending that knowledge.
Dr Albert, who is the director of the division of cognitive neuroscience, department of neurology, at Johns Hopkins University School of medicine, stated, " We are already learning that there may be ways of maintaining general brain health that can be safely recommended to everyone and could have a real impact on helping people maintain the brain's repair mechanisms, resilience and responsiveness. Vitamin E, an antioxidant, has already been tested and shown to somewhat reduce AD symptoms. Increased mental activity may achieve a protective effect by increasing the connections between nerve cells. We know that vitamin E is relatively safe and physicians can feel comfortable recommending it. And, of course, there just doesn't seem to be any downside to increased mental and physical activity. “
French paradox explained?
A letter to the December 2003 issue of the journal Atherosclerosis offered a possible explanation for the so-called French paradox, which is so named because of the apparent paradox of the relatively low incidence of heart disease among the French, who consume a greater amount of fatty foods than the populations of many other countries. It has been hypothesized that the frequent consumption of red wine by the French may be responsible for offering a degree of protection against coronary heart disease (CHD).
Researchers at the University of Illinois at Chicago studied the effect of a methanol soluble pinor noir red wine extract, a concentrated extract, and resveratrol from red wine on two strains of cultured cells infected with Chlamydia pneumoniae, a bacterium responsible for up to 30 percent of acute respiratory tract infections that has also been found to be associated with atherosclerotic plaque development and coronary heart disease. Both the concentrated pinot noir extract and the resveratrol proved to be active against the two Chlamydia strains.
The first time that red wine extracts and resveratrol had been reported to be active against a human pathogen was in 2001, when two of the researchers involved in the current study found that the compounds inhibited the growth of the bacterium, Helicobacter pylori. The authors conclude that, “the French Paradox may be due in part to the beneficial effects of red wine consumption on development and progression of CHD through its antimicrobial activity on C. pneumoniae .” ( Schriever C et al, “Red wine, resveratrol , Chlamydia pneumoniae and the French connection,” Atherosclerosis 171 (2003) 379-380.
Lycopene levels inversely related to women's cardiovascular disease risk
An examination of data obtained from the Women's Health Study, published in the January 2004 issue of the American Journal of Clinical Nutrition, has found an association between higher levels of plasma lycopene and a reduced risk of cardiovascular disease. Lycopene is a carotenoid found in tomatoes and other plant foods that has been linked with a lower risk of several diseases, such as prostate cancer.
Blood samples were obtained from 28,345 participants in the Women's Health Study who were free of cardiovascular disease at enrollment. During the 4.8 year follow-up period, 483 cases of cardiovascular disease (including myocardial infarction, stroke, revascularization, cardiovascular disease death and angina pectoris) were identified. The researchers matched these with an equal number of subjects by age, follow-up time and smoking status. The blood samples were analyzed for plasma lycopene, other carotenoids, and additional factors.
Women who developed cardiovascular disease tended to have a history of disease factors and weigh more at the beginning of the study than women who did not develop the disease. When women in the highest one-fourth of plasma lycopene levels were compared to women in the lowest one-fourth, those whose lycopene levels were highest experienced a 38 percent reduction in the risk of developing cardiovascular disease. When angina was excluded from the analysis, women in the top three-fourths of plasma lycopene had half the risk of developing cardiovascular disease than women in the lowest one-fourth.
Because lycopene is one of the most potent singlet oxygen quenchers, its superior antioxidant property may be responsible for its association with a reduction in cardiovascular disease. Lycopene has been shown to have other properties in vitro that may help lower the risk of the disease, and other studies have demonstrated a link between elevations of the inflammatory marker C-reactive protein and low concentrations of plasma lycopene in human populations.
Glucosamine aids ibuprofen's pain relief
The November 2003 issue of Journal of Pharmacology and Experimental Therapeutics reported that the findings of Temple University researchers that the popular nutritional supplement glucosamine, administered with ibuprofen, synergistically boosts the ability of the drug to relieve pain. Glucosamine is a substance that occurs naturally in the body, and is taken to help relieve arthritis pain, often in combination with chondroitin sulfate, another naturally occurring compound.
The team initially tested glucosamine's ability to relieve irritant-induced pain in mice and found that the compound was ineffective. Glucosamine's known property of relieving the pain of arthritis is caused by its ability to prevent and repair bone and cartilage damage through the activation of chondrocytes and inhibition of inflammation, not due to a direct pain-blocking effect. They then tested the compound with varying doses of several nonsteroidal anti-inflammatory pain relievers and found a synergistic benefit when glucosamine was combined with ibuprofen.
Because nonsteroidal anti- inflammatories are so effective at relieving pain, individuals who have need of them often take increasingly higher doses in hope of relieving more pain. High doses of the drugs can cause gastrointestinal problems such as heartburn and bleeding. A means of rendering a lower dose more effective would enable pain-afflicted individuals to experience greater relief with fewer unwanted effects. Coauthor Robert Raffa PhD, of Temple University 's School of Pharmacy , commented, "Combining pain relievers into one pill can increase patient compliance, simplify prescribing, and improve efficacy without increasing side effects, or conversely, decrease side effects without losing efficacy.”
Alan Cowan PhD, of Temple University School of Medicine, added, “"The next step will be to study this drug combination in clinical trials to see whether it can enhance pain relief or offer pain relief using a lower dose of ibuprofen and therefore a lower risk of side effects.”
Vitamin E decreases oxidative stress in plasma, not plaques
A reason for the benefit provided by vitamin E in early but not advanced atherosclerosis has been proposed by the authors of a study published in the January 2004 issue of the journal, Arteriosclerosis, Thrombosis and Vascular Biology . Italian researchers matched patients scheduled for carotid endarterectomy (surgical removal of an atherosclerotic area inside of a carotid artery) with healthy controls and assigned some of them 900 milligrams per day vitamin E in the form of alpha- tocopherol for six weeks. At the study's onset, participants were tested for levels of alpha- tocopherol and cholesterol oxidation products (measured as 7-beta-hydroxycholesterol and 7-ketocholesterol.) Subjects with atherosclerosis were found to have plasma vitamin E levels that were half that of the healthy participants, as well as having higher levels of 7-beta-hydroxycholesterol, and this group continued to have a lower vitamin E/cholesterol ratio after six weeks.
At the end of the treatment period, scheduled endarterectomies took place and plasma samples were evaluated for vitamin E, 7-beta-hydroxycholesterol and 7-ketocholesterol. Plaques obtained following the surgery were also analyzed for these factors and compared to normal carotid artery tissue. In the group who received vitamin E, plasma levels of the vitamin increased by 88% while 7-beta-hydroxycholesterol decreased significantly from previous levels. However, when the plaques were examined, those from patients who received vitamin E had the same levels of the vitamin and cholesterol oxidation products as plaques from subjects who did not receive it.
Oxidative stress is known to be involved in atherosclerosis, yet clinical trials involving supplementation with the antioxidant vitamin alpha- tocopherol have provided conflicting results. Experimental findings have been positive in contrast with findings from studies that involve patients with advanced atherosclerosis. Atherosclerotic plaques, which are more prevalent with advanced disease may acquire vitamin E through a different method of transport than diffusion from plasma. The authors conclude, “These results imply that patients with advanced atherosclerosis in clinical trials with antioxidants do not represent an ideal model for testing the clinical effect of vitamin E, and antioxidant treatment should be tested in patients with early atherosclerosis.” [ Micheletta F et al, “Vitamin E supplementation in patients with carotid atherosclerosis,” Arterioscler Throm Vasc Biol , 24 (1), pp 136-140]
Increased folate intake linked with lower stroke risk in men
The January 2004 issue of the American Heart Association journal Stroke published the results of a study that sought to determine the role of vitamins B6, B12 and folate in stroke prevention. The study included 43,732 men between the ages of 40 and 75 who were enrolled in the Health Professionals Follow-Up study. Dietary information was obtained through the use of food frequency questionnaires administered at the study's onset, and twice during the follow-up period which ended in the year 2000.
There were 455 ischemic strokes, 125 hemorrhagic strokes and 145 strokes of unknown origin during the follow-up period. Analysis of dietary data showed that vitamin B12 intake was associated with a lower risk of ischemic stroke, and consumption of folate was significantly associated with lower risk. Men in the top one-fifth of folate intake had 30 percent lower stroke risk than those in the lowest fifth. Multivariate analyses of the data confirmed that the benefit of folate was not explained by overall healthier lifestyles in those whose folate intake was high. However, because vitamin supplements were the major source of folic acid, other components of supplement formulas could be responsible for the benefits observed.
The protective benefit of folate and vitamin B12 against stroke could be due to their inverse association with blood homocysteine , which may damage the blood vessels by accumulating in the endothelial cells and generating free radicals. Earlier studies have determined that elevated plasma homocysteine is a risk factor for ischemic stroke. While vitamin B6 levels have also been correlated with homocysteine levels, the association is less strong than that of folate and vitamin B12.
Selenium concentrations inversely related to esophageal and stomach cancer risk
The January 2004 issue of the American Journal of Clinical Nutrition published the findings of researchers from China and the United States that serum concentrations of the mineral selenium are inversely related to the incidence of esophageal squamous cell carcinoma (ESCC) and gastric cardia (upper stomach) cancer (GCC). The study involved 1,103 subjects selected from the General Population Trial of Linxian, China, which enrolled 29,584 adults aged 40 to 69. Serum selenium levels were measured at the study's onset, and participants were followed for fifteen years.
During the follow up period there were 516 deaths, including 116 from heart disease, 167 from stroke, 75 from esophageal squamous cell carcinoma and 36 from gastric cardia cancer. Age, male gender, low body mass index and smoking emerged as factors that were more likely to be found in those who died compared to survivors. Significant inverse associations were observed between serum selenium levels at the start of the study and the risk of death from esophageal squamous cell carcinoma and gastric cardia cancer. Subjects whose selenium concentrations were in the top 25 percent had a 69 percent reduction in gastric cardia cancer mortality risk compared with those in the lowest fourth. For esophageal squamous cell carcinoma, the reduction in the risk of dying from the disease was 65 percent lower in the top quarter compared to the lowest quarter of selenium levels. A smaller inverse association between selenium levels and heart disease was found. There were no inverse trends observed for stroke or total deaths and serum concentrations of selenium.
Due to selenium levels in this Chinese population being low, the authors “are currently evaluating the feasibility of population-wide selenium supplementation for the region of China with low selenium concentrations and a high incidence of ESCC and GCC.” ( Wei WQ et al, “Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death,” Am J Clin Nutr 2004:79:80-5.)