A study in the November 2004 issue of the Journal of Clinical Endocrinology and Metabolism revealed that one out of three diabetic men have low testosterone. The study also showed that the deficiency, known as hypogonadism, is not caused by a testicular defect but by a malfunction of the pituitary gland.
Researchers at the University at Buffalo and Kaleida Health in Buffalo, New York, measured the serum testosterone and other associated hormone levels of 103 men with type 2 diabetes. None of the men had previously been diagnosed with low testosterone. It was discovered that 33 percent of the men had low levels of the hormone. University of Buffalo assistant professor of medicine and study coauthor, Sandeep Dhindsa, MD, explained the research team’s findings: "The surprisingly high prevalence of low testosterone levels was associated with lower levels of pituitary hormones called gonadotrophins, suggesting that the primary defect in these patients was either in the pituitary or higher up in the hypothalamus. Since gonadotrophins drive the testes to produce testosterone, this finding gives us an insight into the pathogenesis of this complication of type 2 diabetes."
The finding is important because hypogonadism had not previously been linked with type 2 diabetes. Low levels of testosterone are associated with a number of adverse health conditions, including diminished libido, erectile dysfunction, loss of muscle tone, increased abdominal fat, low bone density, poor mood and decreased cognitive function.
Dr Dhindsa added, "Further studies will help us determine why type 2 diabetic patients are more prone to developing hypogonadism. While obesity may explain part of the high prevalence of hypogonadism, it is likely that other factors associated with type 2 diabetes also contribute significantly. This area is clearly ripe for further investigation.
A review published in the October 2004 issue of the Journal of the American College of Nutrition has found that the beneficial effects of magnesium could outweigh those of statin drugs. Statins are a class of drugs commonly prescribed for individuals with elevated cholesterol levels, a risk factor for cardiovascular disease. Because the drugs have side effects, some people are seeking alternative ways to improve their cardiovascular disease risk.
Andrea Rosanoff, PhD, and Mildred S Seelig, MD of State University of New York Downstate Medical Center in Brooklyn discuss the fact that statin drugs as well as magnesium inactivate the enzyme 5-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). HMG CoA reductase converts HMG-CoA into a substance called mevalonate, which is the first step in cholesterol formation. Reducing mevalonate improves endothelial function, reduces inflammation, and provides other cardiovascular benefits. Magnesium, however, is also involved in the activity of another enzyme known as lecithin cholesterol acyl transferase (LCAT), which helps elevate high density lipoprotein (HDL) cholesterol levels and reduces low density lipoprotein (LDL) cholesterol and triglycerides. In addition, another enzyme known as desaturase, which helps convert linoleic acid and linolenic acid into prostaglandins, is dependent upon magnesium. Furthermore, optimal levels of magnesium within the cell are a natural calcium channel blocker, which helps dilate the blood vessels.
Drs Rosanoff and Seelig note that while statin drugs help to prevent blood clots, lower inflammation and protect against atherosclerosis, they can elevate liver enzymes and cause myopathy as well as other side effects, whereas diarrhea or mild gastrointestinal distress are the only side effects that have been caused by magnesium supplements. Statins cost at least $100.00 per month compared to no more than $20.00 for a month’s supply of magnesium. These factors combined suggest that increasing magnesium could be a viable alternative to taking statin drugs
A report published in the November 26 2004 issue of the journal Science (http://www.sciencemag.org/) details the findings of researchers from Columbia University Medical Center that stomach cancer originates from stem cells originating in bone marrow rather than stomach stem cells as had been believed.
Cancer experts had assumed that the majority of cancers originate from tissue stem cells. In the case of stomach cancer, it was believed that cancer issued from gastric stem cells found in the lining of the stomach.
Using a mouse model of stomach cancer, Timothy C. Wang, MD and colleagues observed that chronic infection with H pylori led to the stomach being populated with bone marrow derived cells (BMDCs) which progressed into intraepithelial cancer.
Dr Wang, who is the chief of the Division of Digestive and Liver Diseases at Columbia University College of Physicians and Surgeons, stated, “This was an unexpected finding, which may lead to a re-evaluation of current assumptions about how all cancers originate. The implications of this study may lead to new methods of diagnosis and treatment of many cancers – particularly those that have been linked to chronic inflammation such as stomach, esophagus, lung, pancreas, liver, etc."
During infection with the Helicobacter pylori, which has been linked with stomach cancer, bone marrow derived cells arrive in large quantities in the stomach to attempt to repair the inflammation and ulcers caused by the bacteria that lead to the death of normal stomach cells. Being prone to transformation, the bone marrow derived stem cells become stomach cancer cells.
Dr Wang announced, "With this clearer understanding of the connection between bone marrow derived stem cells and stomach cancer, I plan to establish screening models for people at high risk of cancer and work to translate the findings into new treatments that specifically target these cells."
In a seminar published in the November 20 2004 issue of The Lancet, a group of American authors announced that 70 percent of the common birth defect known as neural tube defects (also known as spina bifida) could be prevented if women took folic acid supplements before conceiving and during early pregnancy.
The neural tube is the embryonic structure that becomes the brain and spinal cord. Malformations during its development result in a number of adverse effects later in life, even with modern repair techniques. Although the cause of the defects in most infants is unknown, chromosome abnormalities and gene disorders are to blame in many cases.
Laura Mitchell of Texas A&M University System Health Science Center and colleagues suggest that genes that regulate folate transport and metabolism are involved in folic acid’s protective mechanism against the defects. Randomized clinical trials and other studies have demonstrated that women’s failure to take folic acid supplements results in a two to eight-fold increased risk of giving birth to a child with the disorder. Studies have also shown an inverse relationship between the risk of neural tube defects and blood folate levels, and with dietary plus supplemental folic acid intake.
The authors discuss the need for both surgical and medical management of the disorder, and note that in utero closure of neural tube defects is being conducted in the United States. They conclude, "Spina bifida is the only birth defect for which there have been tremendous successes in both treatment and prevention. Continuing advances in our understanding of the human genome are providing new opportunities to understand the causes of this disorder, and offer the prospect of developing improved strategies for the prevention of spina bifida.”
Grape juice raises HDL and lowers inflammation
The November 2004 issue of Arteriosclerosis, Thrombosis and Vascular Biology (http://atvb.ahajournals.org/) published the results of a study conducted by researchers form Boston University School of Medicine which found that drinking grape juice significantly elevated high density lipoprotein (HDL) cholesterol and lowered inflammation in individuals with stable coronary artery disease. HDL is the so-called good cholesterol that confers a protective benefit effect against cardiovascular disease.
In a double-blind study, 20 individuals with coronary disease were given Concord grape juice or a placebo to drink for fourteen days. This was followed by a two week washout period after which those who had received placebos were given juice and those who received juice were given placebos. Boston University associate professor of medicine and pharmacology, and study coauthor Jane E. Freedman, MD, explained the results: "In addition to HDL levels increasing, we saw significant decreases in the production of superoxide, a free radical, and soluble CD40 ligand, an inflammatory marker about which there is growing interest. Platelet release of soluble CD40 ligand is thought to contribute to the development of atherosclerosis and vascular inflammation. We have seen in previous studies of healthy subjects that drinking grape juice decreases superoxide production and inhibits platelet aggregation, yet its impact on the inflammatory properties of platelets had not been previously studied. The soluble CD40 ligand information is new and particularly interesting, given the growing interest in the link between this inflammatory marker and cardiovascular disease."
Grape juice from Concord grapes has been recently documented by the USDA to contain a higher amount of proanthocyanidins per serving than any other beverage tested. Proanthocyanidins are one of many plant compounds known as polyphenols that have antioxidant and other beneficial properties. The authors note that the cardiovascular disease reduction associated with drinking red wine has been attributed to the polyphenols found in red wine and purple grapes.
Higher selenium levels equal lower colorectal cancer risk
The Journal of the National Cancer Institute published an analysis of data derived from three randomized trials, which revealed that an elevation of blood selenium confers protection against the recurrence of colorectal adenomas, which are precursors of colorectal cancer. The findings were reported in the November 17 2004 issue of the journal.
The current study analyzed three trials that examined the ability of nutritional therapies to prevent colorectal adenoma recurrence: the Wheat Bran Fiber Trail, the Polyp Prevention Trial and the Polyp Prevention Study. Serum selenium levels were ascertained from blood samples provided by 1,763 participants upon enrollment. The reoccurrence of adenomas were ascertained by colonoscopies conducted during the studies' follow up periods.
In all trials, participants whose selenium levels were the highest experienced the lowest risk of developing a new colorectal adenoma. It was discovered that subjects whose blood selenium was in the top one-fourth of participants had a 34 percent lower risk of a new adenoma than those whose selenium was in the lowest quarter.
In an accompanying editorial entitled, “Can selenium prevent colorectal cancer? A signpost from epidemiology,” Scott M Lippman, MD and and Imad Shureiqi of the University of Texas M.D. Anderson Cancer Center, and Anna J Duffield-Lillico of Memorial Sloan-Kettering Cancer Center observe that oxidative metabolism of arachidonic and linoleic acids contribute to the formation of colon tumors. Selenium and selenium-containing compounds, are well known for their antioxidant activity. There is also evidence that the inhibition of cell growth observed in selenium-treated cultured cells is accomplished in part by a reduction in mechanisms dependent upon cyclooxygenase 2 (COX-2).
Dr Lippman and colleagues predict that the findings of this analysis should intensity the interest in clinical trials of selenium and/or other compounds in the prevention of colorectal adenomas
Vitamin K2 intake linked with lower heart disease risk
A study published in the November 2004 issue of the Journal of Nutrition (http://www.nutrition.org/) found that increased dietary intake of vitamin K2 (menaquinone) is associated with a lower risk of coronary heart disease (CHD).
Researchers from the Netherlands tested their hypothesis that a deficiency of vitamin K leads to increased calcification of atherosclerotic lesions thereby raising the risk of heart disease. They examined data obtained in the Rotterdam Study, which enrolled 4,983 men and women 55 years of age and older from 1990 to 1993. The current study analyzed the dietary data of 4,807 participants with no history of heart attack, and followed them until 2000.
During the follow-up period there were 144 nonfatal first heart attacks, 54 fatal heart attacks and 45 other fatal coronary events. Other causes claimed the lives of 602 additional participants. While both vitamin K1 ( phylloquinone ) and vitamin K2 were found to be positively associated with high density lipoprotein (HDL), only vitamin K2 was also associated with a decrease in total cholesterol. Individuals in the top one-third of vitamin K2 intake experienced a 41 percent reduction in incident CHD (defined as fatal and nonfatal heart attacks, sudden cardiac deaths and other forms of ischemic heart disease) compared to those whose intake was the lowest. Mortality from coronary heart disease as well as mortality from all causes was significantly reduced for those whose vitamin K levels were highest. Additionally, severe aortic calcification was found to be inversely related to vitamin K2 intake, and was positively associated with the risk of dying from coronary heart disease.
The results of this study suggest that vitamin K2 helps protect against coronary heart disease in older individuals without increasing the risk of other diseases as shown by the decrease in all-cause mortality associated with higher vitamin K2 intake.
Is antisocial behavior preventable through early childhood nutrition?
A study published in the November 2004 issue of the American Journal of Psychiatry (http://ajp.psychiatryonline.org/) revealed that a deficiency of essential nutrients early in life is linked to behavior problems and reduced IQ later.
Researchers at the University of Southern California followed boys and girls on the Indian Ocean island of Mauritius for 14 years. Nutritional status at age 3 was assessed by the presence of physical indicators of B vitamin, protein, zinc and iron deficiencies. Cognitive ability and intelligence were tested, and background and living conditions assessed.
Three hundred fifty-three participants exhibited signs of malnutrition, compared to 1,206 who did not. Home behavior was assessed at age 8, school behavior and cognitive function at age 11, and home and school behavior at 17. Compared to children who did not show signs of nutritional deficiencies at age 3, children who were malnourished were 41 percent more likely to demonstrate aggression at the age of 8. At age 11, malnourished children showed at 10 percent increase in aggression and delinquency, and at age 17, there was a 51 percent increase in violent and antisocial behavior compared to adequately nourished children. Having a greater number of malnutrition indicators was associated with increased antisocial behavior. Social class was not associated with the children's behavior in this study, however intelligence levels appeared to be a factor.
Study coauthor and University of Southern California professor of psychology Adrian Raine, explained, "Poor nutrition, characterized by zinc, iron, vitamin B and protein deficiencies, leads to low IQ, which leads to later antisocial behavior. These are all nutrients linked to brain development."
“There's more to antisocial behavior than nutrition, but we argue that it is an important missing link,” Dr Raine added. “Biology is not destiny. We can change the biological disposition to antisocial and aggressive behavior."
DHEA supplements may help reduce bulging tummies
A study published in the November 10 2004 issue of the Journal of the American Medical Association (http://jama.ama-assn.org/) found that supplementing with the over the counter hormone dehydroepiandrosterone (DHEA), may help reduce the abdominal fat that increases with age and is associated with insulin resistance and atherosclerosis. DHEA, a hormone produced by the adrenal glands that declines with aging, had previously been found to shrink abdominal fat in laboratory animals, but its effect on humans has not been confirmed.
Dennis T. Villareal , MD, and John O. Holloszy, MD, of Washington University School of Medicine in St. Louis, randomized 28 men and 28 women aged 65 to 78 to receive 50 milligrams per day DHEA or a placebo for six months. Visceral abdominal fat, which occurs within the abdomen, and subcutaneous fat, which exists under the skin, were measured by magnetic resonance imaging before and following the treatment period, and glucose and insulin responses were determined by administering oral glucose tolerance tests.
At the study's conclusion, participants who received DHEA had experienced significant losses visceral and subcutaneous fat. Women who received DHEA lost an average of 10.2 percent visceral fat, and men lost an average of 7.4 percent. Subcutaneous fat loss averaged 6 percent for men and women. Those who received placebos gained small amounts of fat in both areas.
DHEA also improved insulin action. No significant adverse events were associated with DHEA, and the hormone did not cause an elevation in the male participants' prostate specific antigen levels. The authors write, "These findings provide evidence that DHEA replacement may partially reverse the aging-related accumulation of abdominal fat in elderly people with low serum levels of DHEAS. They also raise the possibility that long-term DHEA replacement therapy might reduce the accumulation of abdominal fat and protect against development of the metabolic/insulin resistance syndrome.”
Alpha-linolenic acid helps protect women from cardiac death
The American Heart Association's Scientific Sessions 2004 was the site of a presentation on November 8 of the findings of Harvard researchers that higher dietary levels of alpha-linolenic acid appear to help protect women from dying of heart disease and sudden cardiac death. Alpha- linolenic acid (ALA) is an omega-3 fatty acid found in flaxseed, canola oil, green leafy vegetables and other foods.
The team studied dietary information obtained from the Nurse's Health Study, which included 76,763 women. During the study's sixteen year follow-up, 1,325 women experienced a nonfatal heart attack, 169 underwent sudden cardiac death and 564 died from coronary artery disease.
Alpha- linolenic acid intake was found to range from 0.7 grams per day to 1.5 grams per day. Women whose intake was in the top one-fifth of participants were discovered to have a 46 percent lower risk of dying from sudden cardiac death compared to those in the lowest fifth, and their risk of dying from coronary heart disease was 21 percent lower.
Dr Christine M. Albert, MD, assistant professor of medicine at Harvard University Medical School, and the study's lead author, explained the team's findings: "In this study, we examined whether ALA was associated with a lower risk of dying from heart disease or sudden cardiac death, which is death resulting from an abrupt loss of heart function. Sudden cardiac death is usually the result of a fatal rhythm disturbance. So, if this fat were to prevent sudden cardiac death, it would support the hypothesis that these oils were preventing fatal arrhythmias. “
"A clinical trial that randomly assigns people to ALA supplements or to a diet high in ALA would be needed to know for sure that ALA lowers risk of coronary heart disease and sudden cardiac death," Dr Albert added.
Aging biomarker discovery
A research article published in the November 2004 issue of the Journal of Clinical Investigation, reported that as aging increases, so do two proteins known as p6INK4a and ARF. Researchers at the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center discovered that the proteins increase more than a hundredfold in some tissues as people get older, and have the potential for becoming biomarkers of aging.
Senior author and assistant professor of medicine and genetics at UNC's School of Medicine, Dr Norman Sharpless, stated, "At the very least, our work suggests that looking at the expression of one or both proteins will make a great biomarker of aging - a tool to clinically determine the actual molecular age of people, as opposed to just their chronological age. We all know people that we consider to be a young 65, and we believe they won't demonstrate as much p16INK4a or ARF expression as others of the same age."
The two proteins are strong tumor suppressors known to be involved in cellular aging. The current study shows that they are increased during aging of the whole organism as well. By halting cell growth, the proteins may accelerate the aging process. Dr Sharpless explained, "Proliferation of cells is important in the repair and regrowth of tissues. In fact, we grow old in part because our bodies' ability to regenerate tissues decreases as we age. We believe an untoward effect of increased p16INK4a and ARF expression outside of cancer is a decrease in cellular proliferation needed to sustain this regeneration."
Dr Sharpless' team also discovered that the life extending therapy of calorie restriction significantly reduces the age-related increase in p16INK4a and ARF production, suggesting that decreased expression of the proteins is involved in some of its benefits.
Free radicals likely emphysema culprit
Readers of What's Hot for July 28, 2004 may recall that a deficiency of vitamin A was proposed to be a cause of emphysema. Now a study published in the November 1 2004 issue of the Journal of Clinical Investigation (http://www.jci.org) has found that a gene that protects against free radical damage also helps protect against the disease in mice.
Emphysema, a chronic obstructive pulmonary disease, is mainly caused by cigarette smoking. It has been suggested that the susceptibility of the lungs to damage caused by smoking depends upon oxidative stress caused by excessive free radicals. Oxidative stress markers, such as hydrogen peroxide and 8-isoprostane, have been found to be elevated in chronic obstructive pulmonary disease patients' breath and serum. Several studies have determined that upregulation of the body's protective antioxidant systems protect the lungs from oxidative injury.
Working with mice, Shyam Biswal and colleagues at John Hopkins University disrupted the Nrf2 gene which manufactures a protein which regulates genes that protect the body from damage by free radicals. These mice and mice with an intact Nrf2 gene were exposed to cigarette smoke for six months, following which the lungs were examined. The team found that mice in whom the gene was deleted experienced an earlier onset of emphysema, and that the disease was more widespread than that which developed in the control group of mice. A greater amount of apoptosis of cells in the alveoli of the lungs and more bronchoalveolar inflammation was also observed in these mice. Gene microarrays conducted by the researchers showed that a number of cell protective and antioxidant genes are activated in mice with intact Nrf2.
The study's findings identify Nrf2 as a determinant of susceptibility of the lungs to oxidative stress, and confirm the role of free radical injury and inflammation in emphysema.
Test for vitamin B12 fails to find many cases of deficiency
Researchers at St Louis University have determined that the test currently used to measure vitamin B12 in the body is not sensitive enough to measure a deficiency. A deficiency of vitamin B12 can result in serious consequences such as peripheral neuropathy, spinal cord disease and dementia. The research was presented at the American Neurological Association's meeting held in October, 2004.
St Louis University School of Medicine associate professor of neurology Florian Thomas, MD, PhD, and colleagues found that 26 of 34 patients whose vitamin B12 levels tested normal had elevated levels of methylmalonic acid, a compound that increases when B12 is deficient. Dr Thomas concluded, “The usual way of diagnosing B12 deficiency may be inadequate because it underestimates the frequency of the problem, which is present in up to 20 percent of the elderly. The problem is eminently treatable at pennies a day."
He added, "While it occurs at any age, B12 deficiency is more common in the elderly, may affect some vegetarians and their newborns, can be provoked by laughing gas anesthesia and also by a unique form of recreational drug use. Importantly, it is very easy to treat by taking one pill per day for life. We need to do a better job of detecting the problem."
Vitamin B12 deficiency is seen in younger people as a side effect of the inhalation of nitrous oxide (so-called laughing gas), which is abused as a recreational drug. Deficiency of the vitamin is also seen in patients who have undergone stomach stapling surgery, because an intact stomach better absorbs the vitamin from food.
Dr Thomas and colleagues urge physicians to measure both serum B12 and methylmalonic acid in patients prior to procedures requiring the administration of nitrous oxide, and to test older people every two years.