January 31, 2007

Men warned of osteoporosis risk

Although osteoporosis has long been considered a woman's disease, Professor of Clinical Medicine Aliya A. Khan of McMaster University in Ontario warns that osteoporosis can severely afflict men as well, and wants physicians to realize that they can no longer overlook the disease in male patients. While a fourth of older women are estimated to have osteoporosis, one in eight men over the age of 50 has the disease, and one in three men die following a fracture compared to one in five women.

In a review published in the January 30, 2007 issue of the Canadian Medical Association Journal Dr Khan and her Canadian colleagues developed guidelines for the diagnosis, treatment and management of male osteoporosis, supplementing guidelines published by Osteoporosis Canada in 2002 with information from the current literature. The review identifies primary risk factors such as advancing age, previous fragility fractures and long term glucocorticoid therapy, and secondary causes such as hyperparathyroidism, vitamin D inadequacy, and increased urinary excretion of calcium. Bone mineral density testing for all men over 65 and younger men with osteoporosis risk factors is recommended, as well as long term monitoring of height to detect compression fractures of the spine.

Treatment options earning an "A" in the 2002 Osteoporosis Canada Guidelines are bisphosphonate drugs and 800 international units or more per day vitamin D.

Dr Kahn noted that researchers are "just at the tip of the iceberg" in their understanding of osteoporosis in men compared to their knowledge of how the disease affects women and how to treat it. "The problem is that when men sustain fractures they are more likely to die or suffer a disability," she observed.

In summarizing the researchers' goal, Dr Kahn stated "We want to bring all the research we have to the forefront and we want to bring it to the desk of Canadian physicians."

—D Dye

January 29, 2007

Lifestyle improvements as good as drugs to reduce diabetes risk

A meta-analysis published online on January 19, 2007 in the British Medical Journal concluded that making positive lifestyle changes is at least as effective as using prescription drugs to prevent or delay the onset of type 2 diabetes.

Clare L. Gillies and colleagues at the University of Leicester in England analyzed data from 17 clinical trials which studied the effects of diet and exercise, diabetes drugs, and the anti-obesity drug orlistat on a total of 8,084 men and women with impaired glucose tolerance. When the effects of all forms of lifestyle interventions on the individuals who adopted them were pooled they were found to reduce the risk of developing diabetes by 49 percent compared to individuals who received standard advice only. Exercise alone or exercise combined with dietary improvements appeared to be more effective than diet alone. Oral antidiabetes drugs were also effective at preventing or delaying diabetes, although the risk reduction determined by the analysis was not as great as that found for lifestyle changes. The drug orlistat alone had a comparable effect with that of lifestyle interventions. Diet and exercise also had the advantage of being associated with fewer adverse effects than those caused by pharmaceutical drugs, such as gastrointestinal effects or reduced liver function.

The authors ask whether what is fundamentally a lifestyle issue should be treated with a lifelong course of medication, and note that the potential adverse effects of pharmacological interventions in diabetes type 2 need to be completely understood to be able to assess their benefits and risks. Even minor adverse effects become more significant if a medication is to be taken for life.

"In 2000 an estimated 171 million people in the world had diabetes, and the numbers are projected to double by 2030," they write. "Interventions to prevent type 2 diabetes will therefore have an important role in future health policies."

—D Dye

January 26, 2007

Greater folic acid intake by pregnant women reduces risk of cleft lip in infants

While the preventive benefit of folic acid on neural tube defects in newborns is well known, scientists have recently discovered that women who consume folic acid supplements early in their pregnancies significantly reduce the risk of cleft lip in their infants. Cleft lip often accompanies cleft palate, a common birth defect. The research was published online this month in the British Medical Journal.

The study included 377 infants born with cleft lip with or without cleft palate, 196 infants with cleft palate, and 763 healthy babies born between 1996 and 2000 in Norway. The infants' mothers were questioned concerning their smoking, drug use, diet, and multivitamin and folic acid supplement use during the first three months of their pregnancy. Food frequency questionnaires completed by the mothers were analyzed for folate content.

Adjusted analysis found that women supplementing with at least 400 micrograms of folic acid per day reduced the risk of cleft lip in their infants by 40 percent. Folate from diet alone had a more moderate protective benefit, with a 25 percent risk reduction in infants born to women whose intake was among the top half of the group. Women who consumed at least a 400 microgram folic acid supplement, whose dietary intake of folate was in the top half of subjects, and who additionally consumed a multivitamin supplement had infants who experienced the lowest cleft lip risk, which was 74 percent lower than that experienced by the children of women who reported practicing none of these measures.

"Intake of 400 micrograms a day or more of folic acid in the periconceptional period seems to reduce the risk of isolated cleft lip with or without cleft palate in Norway by about a third," the authors conclude.

—D Dye

January 24, 2007

Supplementing with folic acid may improve cognitive function

Readers of What's Hot will recall a recent article published on January 3 of this year which summarized the finding of Jane Durga of Wageningen University in the Netherlands and her colleagues that supplementing with folic acid for three years helped slow age-related hearing loss. In the January 20, 2007 issue of The Lancet, Dr Durga's team now reports that folic acid also improves cognitive function in older adults.

Eight hundred eighteen participants in the Folic Acid and Carotid Intima-media Thickness (FACIT) trial were assigned to 800 micrograms per day folic acid or a placebo for three years. Participants were limited to those whose total homocysteine levels were at least 13 and no greater than 26 micromoles per liter. The subjects were tested for memory, sensorimotor speed, complex speed, information processing speed, and word fluency at the beginning of the study and at its conclusion.

Serum folate was increased by 576 percent and plasma total homocysteine was 26 percent lower at the end of the study among participants who received folic acid compared to the placebo group. Of the cognitive function criteria tested, memory, information processing speed and sensorimotor speed were significantly better among those who received the vitamin.

In an accompanying editorial entitled, "Is dietary folate too low?", Martha Clare Morris and Christine C Tangney of Rush University observed that the low folate levels evident in the Dutch study population were below those of the Netherlands' RDA of 300 micrograms per day. "Many individuals within populations have folate intakes that might be suboptimum for physiological function," they write. "Our knowledge about the physiological importance of homocysteine is limited, as is our definition of inadequate folate status. To make more informed dietary recommendations for optimum folate intake, we need randomised trials that take the approach of the FACIT trial."

—D Dye

January 22, 2007

Nutritional regimen lowers coronary heart disease risk factors in heart attack patients

A report published in the January, 2007 issue of the Journal of Nutrition revealed the finding of researchers in Granada, Spain that providing patients enrolled in a cardiac rehabilitation program with a combination of nutrients abundant in the Mediterranean diet reduced total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein after one year.

Forty male patients who had suffered a myocardial infarction (MI) and were attending exercise classes at a cardiac rehabilitation unit were divided to receive semi-skimmed milk fortified with vitamins A and D, or the same milk additionally fortified with EPA and DHA from fish oils, oleic acid, folic acid, vitamin B6 and vitamin E to be consumed twice per day. Blood samples were evaluated for plasma triglycerides, cholesterol, apolipoprotein B, homocysteine, high-sensitivity C-reactive protein and other factors at the beginning of the study and quarterly for one year.

At the study's conclusion, plasma total cholesterol, LDL cholesterol, and apoliprotein B and C-reactive protein were reduced compared to baseline levels in the group who received the supplemented drink. Homocysteine levels declined in both groups, and there were no changes in heart rate or blood pressure, nor did further cardiovascular events occur.

"Although numerous studies have been carried out using the nutrients used in the supplement, to the best of our knowledge, no dietary intervention using a combination of them has been reported in MI patients," the authors report. "This study indicates that therapeutic lifestyle changes, effected through a cardiac rehabilitation program comprised of regular exercise and the intake of low amounts of a combination of healthy nutrients are able to reduce a variety of risk factors in MI patients, and supports the rationale for the use of nutritional programs in the secondary prevention of CHD."

—D Dye

January 19, 2007

EPA reduces newly recognized cardiovascular disease risk factors

A report published in the January, 2007 issue of the journal Diabetes Care summarized the finding of researchers at Kyoto Medical Center and Tokyo Medical and Dental Hospital in Japan that consuming the polyunsaturated fatty acid eicosapentaenoic acid (EPA) is associated with a reduction in small dense low density lipoprotein (sdLDL), remnant lipoprotein particles, and C-reactive protein in men and women with metabolic syndrome. The omega-3 fatty acids EPA and DHA are abundant in fish oils, which have been associated with a beneficial effect on a number of diseases and conditions, including cardiovascular disease. The current research sought to determine whether EPA has an effect independent of DHA on lipoprotein subclass profiles and inflammation in individuals with metabolic syndrome, a precursor of cardiovascular disease (CVD).

The study included 44 type 2 diabetics who satisfied the diagnostic criteria of the metabolic syndrome. Participants were divided to receive a standard diet designed for cardiovascular disease, or diet plus 1.8 grams EPA daily for three months. Body mass index, serum EPA and arachidonic acid (a fatty acid associated with inflammation) levels, remnant lipoprotein particle cholesterol and triglycerides, plasma cholesteryl ester transfer protein (CETP) activity, LDL cholesterol subfractions, and C-reactive protein were measured before and after the treatment regimen.

At the conclusion of the study, serum EPA levels were elevated while arachidonic acid levels were decreased in the group that received EPA. Remnant lipoprotein triglycerides, CETP activity, small dense LDL, and CRP levels were significantly lowered in the group that received EPA compared to the group treated by diet alone. Decreases in in CRP were correlated with reductions in remnant lipoprotein cholesterol and small dense LDL.

"The present study is the first to demonstrate that purified EPA reduces sdLDL, remnants, and CRP, thereby potentially leading to the reduction in development of atherosclerosis and CVD in metabolic syndrome," the authors conclude.

—D Dye

January 17, 2007

Calcium supplements help reduce colorectal polyp recurrence for up to five years

The January 17, 2007 issue of the Journal of the National Cancer Institute published the finding of Maria V. Grau, MD of Dartmouth Medical School in New Hampshire and her colleagues that supplementing with calcium helped prevent the recurrence of colorectal polyps over a long term period. Polyps, or adenomas, are noncancerous tumors that are a precursor of colorectal cancer.

Dr Grau and her colleagues followed 822 men and women who completed the Calcium Poly Prevention Study, which discovered that a daily supplement providing 1200 milligrams calcium reduced the risk of polyp recurrence by 17 percent compared to those who received a placebo over a four year period. In the current Calcium Follow-Up Study, these subjects were followed for an additional average seven year period after the Calcium Polyp Prevention Study treatment period ended.

Over the first five years of follow-up, participants who received calcium supplements in the previous study had a 31.5 percent risk of adenoma recurrence, while those who had received a placebo experienced a 43.2 percent risk, resulting in a 37 percent lower adjusted risk in the calcium group compared with the placebo. Those in the calcium group also had a small reduction in the risk of advanced adenomas, which the authors of the study did not consider statistically significant. The protective effect of calcium did not continue over the second five year period of the current follow-up.

"Our study provides further evidence of the potential of calcium as a chemopreventive agent against colorectal adenomas among individuals with a history of these tumors," the authors conclude. "The protective effect of calcium supplementation on risk of colorectal adenoma recurrence extends up to five years after cessation of active treatment, even in the absence of continued supplementation."

—D Dye

January 15, 2007

Low dose aspirin associated with reduced asthma risk

Low dose aspirin every other day reduced the risk of developing asthma in a large scale clinical trial, concluded Tobias Kurth, MD, ScD of Brigham and Women's Hospital in Boston and colleagues after examining data from the double-blind Physician's Health Study. Asthma is a chronic inflammatory disease that causes breathing difficulties which is estimated to affect over 20 million Americans. Dr Kurth and his coauthors reported the finding in the January 15, 2007 issue of the American Thoracic Society journal American Journal of Respiratory and Critical Care Medicine.

The Physician's Health study involved 22,071 healthy male physicians between the age of 40 and 84 who consumed low-dose aspirin or a placebo on alternate days. The study was terminated after 4.9 years when a dramatic 44 percent reduction in the risk of a first heart attack was found among those who received aspirin. Participants were given the opportunity to report a diagnosis of asthma at the beginning of the study, at six months, and yearly thereafter. One hundred thirteen out of the 11,037 men who received aspirin developed asthma, compared with 145 who received a placebo. The risk reduction was not found to be affected by smoking status, body mass index, or age. "Aspirin reduced the risk by 22 percent of newly-diagnosed adult-onset asthma," Dr. Kurth observed. "These results suggest that aspirin may reduce the development of asthma in adults."

"They do not imply that aspirin improves symptoms in patients with asthma," he added. "Indeed, asthma can cause severe bronchospasm in some patients who have asthma. Because asthma was not the primary endpoint of the U. S. Public Health Service study, additional randomized trials would be helpful to confirm the apparent reduction in asthma incidence caused by aspirin."

—D Dye

January 12, 2007

Gene variant found to protect diabetics from kidney failure

An article published online on January 5, 2007 in the journal Nephrology Dialysis Transplantation reported the finding of researchers from Wake Forest University Baptist Medical Center and the University of Heidelberg that a form of the carnosinase 1 gene offers protection to many diabetics against the development of end-stage kidney failure.

Barry I. Freedman, MD, of Wake Forest University's department of Internal Medicine, and colleagues evaluated the DNA of 294 individuals of European descent with type 2 diabetes-associated end stage renal disease, 258 diabetics without kidney disease, and 306 healthy individuals for the current study. They found the protective form of the carnosinase 1 gene more often among those without kidney disease, whereas diabetics with end stage renal disease were more likely to have a different form.

The carnosinase 1 gene, located on human chromosome 18, produces carnosinase which breaks down carnosine. Carnosine protects the kidneys by preventing the development of scar tissue and scavenging harmful oxygen free radicals. Europeans, American Caucasians, and Arabs with the protective form of the carnosinase 1 gene have higher levels of carnosine.

"This is a major gene that appears to be associated with development of severe diabetic kidney disease," Dr Freedman said. "Prior to these genetic analyses, kidney doctors were unaware that this pathway played an important role in diabetic kidney disease."

A similar analysis conducted among African Americans did not show involvement of the carnosinase pathway in diabetic kidney failure. "It is possible that American blacks have different carnosine metabolism, making them less susceptible to alterations in carnosinase gene activity. Analyses are currently under way," Dr Freedman stated.

"It will be important to evaluate whether the administration of carnosine or agents that inhibit carnosinase activity will protect diabetic individuals from the development of progressive kidney disease," Dr Freedman noted.

—D Dye

January 10, 2007

Breastfeeding women risk oral bone loss

The January, 2007 issue of the Journal of Periodontology published the results of an animal study conducted by researchers at the Department of Oral Biology at Tohoku University Graduate School of Dentistry in Sendai, Japan, that lactation can lead to the loss of bone surrounding the teeth and gums, especially when the diet is deficient in calcium.

Dr Kanako Shoji of Tohoku University's division of Periodontology and Endodontology used a rat model of periodontitis for the current study. Sixty-two female rats were bred with males and divided to receive diets that provided 0.9%, 0.3% or 0.02% calcium. Periodontitis was induced on one side of the mouth in both lactating and nonlactating rats. Following the period of lactation, gum tissue and bone surrounding the teeth was examined and bone mineral density measured.

Although bone mineral density decreased in all rats according to the amount of calcium in the diet, the decrease was greater in the lactating animals. Diets with lower calcium resulted in acute inflammation in the periodontal tissues in addition to increased loss of bone height on the experimental side, with animals who were lactating experiencing greater loss.

"Our research emphasized the importance of having a high-calcium diet while breast-feeding," said Dr Shoji stated. "While our study was on a rat population, the evidence confirmed that breastfeeding can cause increased bone loss in the mother, especially when the mother has insufficient calcium intake. But additional studies in human populations are necessary to confirm these findings."

"We know a high-calcium diet can promote healthy teeth and gums," added Dr. Preston D. Miller, DDS, who is President of the American Academy of Periodontology, "But this research indicates that nursing mothers should be especially conscious of having enough calcium in their diet."

—D Dye

January 8, 2007

Being overweight or gaining weight in adulthood increases prostate cancer death risk

A report that will appear in the February 15, 2007 issue of the American Cancer Society journal Cancer concluded that being overweight or gaining weight after the age of 18 is associated with a greater risk of a man dying from prostate cancer, though not associated with an increased incidence of the disease. The study is the first of its kind to identify increased adult weight gain as an independent poor prognostic factor for prostate cancer.

Margaret E. Wright, PhD, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute in Bethesda, MD, and colleagues analyzed data from the NIH-AARP Diet and Health Study, which followed 287,760 men aged 50 to 71. They found that having a body mass index (BMI) classified as overweight was associated with 25 percent higher risk of dying from prostate cancer, and being mildly obese was associated with a 46 percent increased risk. Severe obesity, defined as a body mass index over 35, doubled the risk of dying from prostate cancer. Gaining weight after the age of 18 was additionally associated with prostate cancer death.

Although a previously conducted meta-analysis found a weak association between obesity and developing prostate cancer, the current study failed to find an association. Other research suggests that having a higher body mass index or gaining weight rapidly after the age of 25 increases the risk of treatment failure or being diagnosed with advanced prostate cancer. The finding that body mass index and adult weight gain were each associated with a greater risk of dying from prostate cancer significantly links "adiposity to prostate cancer progression leading to death," the authors conclude.

—D Dye

January 5, 2007

Fish, fruit and vegetables associated with reduction in venous thrombosis

In Norway during World War II a decrease in the rate of postoperative thrombosis emboli (blood clots) occurred during a period of food rationing in which the populace consumed fewer meats and dairy products and a greater amount of fish, cod liver oil and vegetables. To test their hypothesis that consuming more foods that provide B vitamins and omega-3 fatty acids is associated with a reduction in deep vein thrombosis or pulmonary embolism, researchers at the University of Minnesota in Minneapolis analyzed data from 14,962 participants in the Atherosclerosis Risk in Communities (ARIC) study and to determine that consuming fish, vegetables and fruit was linked with a lower incidence of venous thromboembolism (VTE) over an average 12.5 years of follow-up. The research was reported online on December 18, 2006, in the journal Circulation.

Dietary questionnaires completed by participants at the beginning of the study and during the sixth year were analyzed for food groups and several nutrients. One hundred ninety-six cases of deep vein thrombosis or pulmonary embolism were identified during the follow-up period.

Participants in the top one-fifth of fruit and vegetable intake had a 41 percent lower risk of venous thromboembolism than those whose intake was in the lowest fifth. Eating fish at least once per week was associated with a 30 to 45 percent lower incidence of the condition compared with those who consumed fish less often. When individual nutrients were examined, venous thromboembolism incidence was 34 to 51 percent lower for those who consumed at least 160 micrograms folate per day compared to those who consumed less. Vitamin B6 and omega-3 fatty acid intake also appeared to be protective. Meat intake was associated with increased risk.

"Our findings provide evidence that a diet including abundant plant food and fish and little meat is associated with lower risk of incident VTE," the authors conclude.

—D Dye

January 3, 2007

Folic acid supplementation slows hearing loss

The January 2, 2007 issue of the Annals of Internal Medicine published the finding of researchers at Wageningen University and Wageningen Centre for Food Sciences, and University Hospital Maastricht in the Netherlands that supplementing older men and women with folic acid slowed age-related hearing loss. Previous research has found an association between diminished hearing and reduced levels of the vitamin.

Jane Durga and colleagues recruited 728 Dutch adults between the ages of 50 to 70 from municipal and blood blank registries for the current double-blind, randomized study. Participants were limited to those with total plasma homocysteine levels of at least 13 micromoles per liter and vitamin B12 concentrations of 200 picomoles per liter, and no middle ear dysfunction, hearing loss in one ear, or non-age related ear pathologic diseases. Subjects were given a daily supplement providing 800 micrograms folic acid or a placebo for three years. Tests measuring the ability to hear low and high frequencies were conducted upon enrollment and at the study's conclusion.

Median hearing thresholds were 11.7 decibels for low frequencies and 34.2 decibels for high frequencies at the beginning of the study. Hearing thresholds for low frequencies increased by 1 decibel in the group that received folic acid and by 1.7 decibels in the group that received the placebo. There was no significant difference in the decline in the ability to hear high frequencies between the two groups.

Because the Netherlands does not mandate the fortification of grains with folic acid, it is unknown whether the effect seen in this investigation will occur in populations with higher folate levels. It is also not known whether individuals with lower homocysteine levels than those of the study's participants will be effected. The authors recommend further research, particularly in populations residing in countries with folic acid fortification.

—D Dye

January 1, 2007

Multinutrient supplement reduces odds of giving birth to low weight babies

A report published in the January, 2007 issue of the American Medical Association journal Archives of Pediatrics & Adolescent Medicine revealed the finding of Piyush Gupta, MD and colleagues at the University College of Medical Sciences in Delhi, India, that a prenatal multivitamin and mineral supplement given to undernourished pregnant women is more effective than iron and folic acid supplementation alone to help prevent delivering a low birth weight infant. Low birth weight is a risk factor for infant death, as well as the development heart disease, stroke and diabetes later in life.

The researchers assigned 99 underweight or iron deficient pregnant women to receive a daily tablet providing 29 micronutrients while the remaining 101 participants received a daily calcium tablet. All subjects received iron and folic acid supplements as well as prenatal health guidance and monitoring.

Participants who received the multinutrient supplement gained an average of 20.3 pounds during their pregnancies, while those who received only calcium in addition to folic acid and iron gained 19.2 pounds. Infants born to mothers who received the micronutrients weighed an average of 98 grams more than those born to mothers who did not receive them. The rate of delivering an infant categorized as having a low birth weight of less than 2,500 grams was 15.2 percent among mothers receiving the multinutrient supplement compared with 43.1 among the other mothers. The incidence of illness during the first week of life of infants born to women who did not receive the micronutrient supplement was almost double that of infants born to mothers who did receive the supplement. Birth weight was correlated with newborn illness.

"We advocate community-based trials in deprived populations to ascertain the impact of a supplementation schedule lasting throughout pregnancy," the authors recommend.

—D Dye

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