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LE Magazine February 2002

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Studies from throughout the world that can help you live longer

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February 2002 Table of Contents

  1. Curcumin protects against lung injury
  2. Melatonin increases muscle and liver glycogen
  3. Role of vitamin C in atherogenesis and vascular dysfunction
  4. Protective effect of aminoguanidine on brain damage
  5. Preventing hip fracture
  6. Antioxidants/caloric restriction protects against liver cancer
  7. Effect of L-carnitine on glycoprotein status
  8. Cardiovascular disease risk factors and menopausal status
  9. Effect of curcumin and dietary n-3 fatty acids on macrophages
  10. Antioxidants and free radicals in exercise
  11. Genetic Link: periodontal disease, clotting factor and heart diesease
  12. Treating chronic insomnia without drugs
  13. Caloric intake and aging
  14. Diet and cancer prevention
  15. Red meat consumption linked to digestive system cancers
  16. Beer may reduce heart disease risk
  17. Americans do not drink enough water
  18. Estrogen use and early onset of Alzheimer's disease

1. Curcumin protects against lung injury

An early feature of paraquat (PQ) toxicity (a weedkiller that produces delayed toxic effects on the lungs when ingested) is the inflow of inflammatory cells, releasing proteolytic enzymes and free radicals, which can destroy lung tissue and result in pulmonary fibrosis (chronic inflammation and formation of fibrous tissue). Therefore, suppressing early lung injury is an appropriate therapy of pulmonary damage before the development of irreversible fibrosis. Curcumin confers remarkable protection against PQ lung injury. In a study, 50 mg/kg of PQ resulted in a significant rise in the levels of certain proteins and enzymes, thiobarbituric acid reactive substances (TBARS), and neutrophils in the fluid of the bronchioles and alveoli in the lungs (bronchoalveolar lavage fluid (BALF), while decreasing glutathione levels. In addition, the data also demonstrated that PQ caused a decrease in angiotension converting enzyme (ACE), glutathione levels and an increase in levels of TEARS and myeloperoxidase (MPO) (leads to impaired bacterial killing) activity in the lung. Interestingly, curcumin prevented the general toxicity and mortality induced by PQ and blocked the rise in proteins and enzymes such as BALF protein, ACE and neutrophils. Similarly, curcumin prevented the rise in TEARS content in both BAL cell and lung tissue and MPO activity of the lung. In addition, curcumin treatment abolished PQ induced reduction in lung ACE and BAL cell, and lung glutathione levels. Thus, curcumin has important therapeutic implications in facilitating the early suppression of PQ lung injury.

LIFE SCIENCES, 2000, Vol 66, Iss 2, pp PL21-PL28


2. Melatonin increases muscle and liver glycogen

The effects of melatonin on several parameters of carbohydrate and lipid metabolism were investigated in exercised and nonexercised rodents. The stress from exercise resulted in a significant hypoglycemia (low blood sugar) and increased blood levels of lactate and P-hydroxybutyrate, together with a significant reduction of glycogen in muscle and liver. In nonexercised animals receiving melatonin (0.5 or 2.0 mg/kg), muscle and liver glycogen content was elevated and blood fatty acid decreased. Melatonin at 2.0 mg/kg reduced blood lactate and increased lactate concentration in liver. When compared to untreated exercised animals, glycemia, muscle, and liver glycogen content were significantly higher in melatonin-treated exercised animals. Blood and liver lactate and blood P-hydroxybutyrate were significantly reduced. The results indicate that melatonin preserves glycogen stores in exercised rats through changes in carbohydrate and lipid utilization.

LIFE SCIENCES, 2000, Vol 66, Iss 2, pp 153-160


3. Role of vitamin C in atherogenesis and vascular dysfunction

Free radicals have been implicated as an important causative factor in atherosclerosis and vascular dysfunction. Antioxidants can inhibit the development of atherosclerosis and improve vascular function by two different mechanisms. 1) Lipid-soluble antioxidants present in low-density lipoprotein (LDL), including vitamin E and water-soluble antioxidants present in the extracellular fluid of the arterial wall, including vitamin C, inhibit LDL oxidation through an LDL-specific antioxidant action. 2) Antioxidants present in the cells of the vascular wall decrease cellular production and the release of free radicals, inhibit endothelial activation (i.e., activity of molecules that adhere to one another), and improve the biologic activity of endothelium-derived nitric oxide (EDNO) through a cell- or tissue-specific antioxidant action. Vitamin E and a number of thiol antioxidants have been shown to decrease the adhesion of molecules. Vitamin C has been demonstrated to make EDNO activity more effective and normalize vascular function in individuals with coronary artery disease and associated risk factors, including hypercholesterolemia, hyperhomocysteinemia, hypertension, diabetes and smoking.

PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE, 1999, Vol 222, Iss 3, pp 196-204


4. Protective effect of aminoguanidine on brain damage

Nitric oxide (NO) produced by inducible NO synthase contributes to ischemic brain damage. However, the role of inducible NO synthase-derived NO on neonatal hypoxic-ischemic encephalopathy has not been clarified. We demonstrate here that aminoguanidine, a relatively selective inhibitor of inducible NO synthase, ameliorated neonatal hypoxic-ischemic brain damage and that temporal profiles of NO correlated with the neuroprotective effect of aminoguanidine. Seven-day-old rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure (8% oxygen). Infarct volumes (cortical and striatal) were assessed 72 h after the onset of hypoxia-ischemia by planimetric analysis of coronal brain slices stained with hematoxylin-eosin. Aminoguanidine (300 mg/kg i.p.) administered once before the onset of hypoxia-ischemia and then three times daily, significantly ameliorated infarct volume (89% reduction in the cerebral cortex and 90% in the striatum). NO metabolites were measured by means of chemiluminescence using an NO analyzer. In controls, there was a significant biphasic increase in NO metabolites in the ligated side at 1 hour (during hypoxia) and at 72 h after the onset of hypoxia (p < 0.05). Aminoguanidine did not suppress the first peak but significantly reduced the second one (p < 0.05), and markedly reduced infarct size in a neonatal ischemic rat model. Suppression of NO production after reperfusion is a likely mechanism of this neuroprotection.

PEDIATRIC RESEARCH, 2000, Vol 47, Iss 1, pp 79-83


5. Preventing hip fracture

Hip fractures are recognized as a major public health problem worldwide. Demographic changes will lead to enormous increases in the number of hip fractures and projections indicate that the number of hip fractures occurring worldwide each year will rise from 1.26 million in 1990 to 4.5 million by 2050. However, preventive strategies are available. Supplementation with calcium and vitamin D restores bone quality by suppressing excessive activity of the parathyroid glands and decreases the risk of falling by improving neuromuscular coordination. As a result, hip fracture risk is reduced by 43% in the vitamin D-insufficient elderly. Treatment with the bisphosphonate alendronate increases bone strength and results in a 51% reduction of hip fracture risk. Also, hip protectors absorb energy during a fall and reduce hip fracture risk by 56%. Combining these procedures could prevent a large proportion of hip fractures in the future.

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 1999, Vol 10, Iss 10, pp 417-420


6. Antioxidants/caloric restriction protects against liver cancer

A study looked at the role of oxidative stress and oxidative damage in the induction of cancer by nongenotoxic carcinogens (Genotoxic = may cause mutation or cancer by damaging DNA). Liver carcinogenic compounds such as chlorinated hydrocarbons appeared to induce oxidative stress in the liver. This oxidative stress and oxidative damage in turn may be responsible for the tumor-promoting activity of these compounds. Reduction of oxidative damage by antioxidants, or dietary-restriction, results in a lessening of the selective cell growth by these carcinogens.

The free radical stress induced by non-genotoxic agents may influence cell proliferation and/or apoptosis (programmed cell death) in the pre-cancerous cells. A study with nongenotoxic liver carcinogens showed a dose-dependent increase in oxidative stress and an increase in liver local lesion growth. The use of antioxidant dietary supplementation or caloric restriction prevented the lesion growth. This restriction appeared to be through an increase in apoptosis (cell death) in the liver lesions.

TOXICOLOGICAL SCIENCES, 1999, Vol 52, Iss 2, Suppl S, pp 101-106


7. Effect of L-carnitine on glycoprotein status

The effect of L-carnitine on glycoprotein status was studied in young and aged rats. The levels of protein, hexose, hexosamine, sialic acid and fucose were low in aged rats. Supplementation of L-carnitine (300 mg/kg body weight/day) for 7, 14 and 21 days demonstrated a normalization of glycoprotein status. There was no such significant effect upon carnitine administration to young rats. It was concluded that L-carnitine is effective in normalizing the age-associated alterations in glycoproteins and can minimize the age-associated disorders in which free radicals are the major cause.

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION, 1999, Vol 26, Iss 3, pp 193-200


8. Cardiovascular disease risk factors and menopausal status

A study examined cardiovascular risk factors in 93 pre- and 93 postmenopausal women age 43-55. Postmenopausal women who were at least 3 years after menopause or whose menses had stopped naturally before age 48 were age-matched with premenopausal women with regular menses and without menopausal complaints. Compared to premenopausal women, postmenopausal women had significantly increased levels of total cholesterol (10.0%), low-density lipoprotein (LDL) cholesterol (14.0%) and apolipoprotein B (8.2%,). The difference was present within 3 years after onset of menopause. However, it did not show a trend towards an increase with the advancement of a number of postmenopausal years. No differences were found in high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1, blood glucose, insulin, body mass index, waist-to-hip ratio and systolic and diastolic blood pressure. The results of this study add to the evidence that total cholesterol, LDL cholesterol and apolipoprotein B are the primary cardiovascular risk factors affected by menopause.

JOURNAL OF INTERNAL MEDICINE, 1999, Vol 246, Iss 6, pp 521-528


9. Effect of curcumin and dietary n-3 fatty acids on macrophages

Macrophages (immune system cells) from rodents fed cod-liver oil (rich in n-3 fatty acids) diet secreted lower levels of lysosomal enzymes collagenase, elastase and hyaluronidase as compared to those from rats fed coconut oil or groundnut oil diets. (A lysosomal enzyme serves to digest exogenous material, such as bacteria). Curcumin significantly lowered the secretion of these lysosomal enzymes from macrophages in animals given coconut oil or groundnut oil diet. Macrophages from rats fed cod-liver oil secreted lower amounts of eicosanoids such as prostaglandin, leukotrienes and also incorporated lesser amounts of arachidonic acid as compared to those given the coconut oil diet. Curcumin lowered the secretion of these eicosanoids and decreased the incorporation of arachidonic acid in macrophage lipids. The study indicates that dietary cod-liver oil (rich in n-3 fatty acids), and the spice, curcumin can lower the secretory functions of macrophages in a beneficial manner.

MOLECULAR AND CELLULAR BIOCHEMISTRY, 2000, Vol 203, Iss 1-2, pp 153-161


10. Antioxidants and free radicals in exercise

Strenuous exercise increases oxygen consumption and causes disturbance of intracellular pro-oxidant-antioxidant homeostasis (stability in the normal physiological states). The mitochondrial electron transport chain, polymorphoneutrophil and xanthine oxidase have been identified as major sources of intracellular free radical generation during exercise. The free radicals are a serious threat to the cellular antioxidant defense system, such as diminished reserve of antioxidant vitamins and glutathione (endogenous), and increased tissue susceptibility to oxidative damage. However, enzymatic and nonenzymatic antioxidants have demonstrated great adaptation to acute and chronic exercise. The delicate balance between pro-oxidants and antioxidants suggests that supplementation of antioxidants may be desirable for physically active individuals under certain physiological conditions by providing a larger protective margin.

PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE, 1999, Vol 222, Iss 3, pp 283-292


11. Genetic Link: periodontal disease, clotting factor and heart diesease

A study found increased levels of the blood-clotting factor, fibrinogen, in persons with periodontitis. Elevated fibrinogen levels in the blood are known to be an independent risk factor for cardiovascular disease by increasing the propensity for blood clots. There is a relationship between cardiovascular disease and the gene for fibrinogen. The study found that persons with periodontal disease are more likely to have a rare form of the gene responsible for fibrinogen activity than persons with no periodontal disease. People with the rare form of the fibrinogen gene (H2H2) produce higher levels of fibrinogen than those with the more-common gene. Results showed that 16% of the periodontal-disease group had the rare form, compared to none of the healthy participants. Since the production of fibrinogen can be stimulated by an infection, people with the rare gene who also have a chronic infection such as periodontal disease may produce higher levels of the clotting factor, thus putting themselves at even higher risk for heart disease. The study provides another potential link between chronic infections, such as periodontal disease, and atherosclerotic heart disease. The findings present the possibility of using these measures as a diagnostic tool to identify people at potential risk for heart disease. The study was supported by a grant from the National Institutes of Health.

ANNUAL MEETING OF THE INTERNATIONAL ASSOCIATION FOR DENTAL RESEARCH, May 2000, Research at U of Buffalo School of Dental Medicine


12. Treating chronic insomnia without drugs

A study at the American Academy of Sleep Medicine indicates that non-pharmacological therapies produce reliable and durable changes for chronic insomnia sufferers. The data indicate that between 70% and 80% of individuals treated with nonpharmacological interventions benefit from treatment. For the typical individual with persistent insomnia, treatment is likely to reduce the main target symptoms of sleep onset latency and/or wake time. Sleep duration is increased by a modest 30 minutes and sleep quality and individual's satisfaction with sleep patterns are significantly enhanced. Sleep improvements achieved with these behavioral interventions are sustained for at least 6 months after treatment completion. Three treatments meet the American Psychological Association (APA) criteria for empirically-supported psychological treatments for insomnia: 1) Stimulus control, 2) progressive muscle relaxation and 3) paradoxical intention. Three additional treatments meet APA criteria for probably efficacious treatments: 1) Sleep restriction, 2) biofeedback and 3) multifaceted cognitive-behavior therapy. Additional outcome research is needed to examine the effectiveness of treatment when it is implemented in clinical settings (primary care, family practice).

SLEEP, 1999, Vol 22, Iss 8, pp 1134-1156


13. Caloric intake and aging

Caloric restriction (CR) increases maximum life span in rodents while lessening the development of age-associated pathological and biological changes. Although nearly all of the rodent studies have initiated CR early in life (1-3 months of age), CR, when started at 12 months of age, also extends maximum life span in mice. Two main questions face investigators of CR: 1) the mechanisms by which CR retards aging and diseases in rodents. There is evidence that CR may act, at least in part, by reducing free radicals. A CR-induced decrease in free radicals appears to be most profound and may derive from lower mitochondrial production of free radicals, 2) whether CR will exert similar effects in primates. Studies on CR in rhesus monkeys (maximum life span similar to 40 years) support the notion of it working in humans. Rhesus monkeys were subjected to a 30% reduction of caloric intake starting at either 1989 or 1994 when they were similar to 10 years old. Data from various trials suggest that CR can be safely carried out in monkeys and that certain beneficial physiological effects of CR that occur in rodents (e.g., decreased blood glucose and insulin levels, improved insulin sensitivity, and lowering of body temperature) also occur in monkeys. Whether free radical stress in monkeys is reduced by CR will be known by the year 2001, while effects on longevity and diseases should be clearly seen by 2020.

TOXICOLOGICAL SCIENCES 1999, Vol 52, Iss 2, Suppl S, pp 35-40


14. Diet and cancer prevention

Diet can play a major role in cancer prevention. The international differences in cancer incidence are largely accounted for by lifestyle practices that include nutrition, exercise and alcohol and tobacco use. About 50% of cancer incidence and 35% of cancer mortality in the U.S., represented by cancers of the breast, prostate, pancreas, ovary, endometrium and colon, are associated with Western dietary habits. Cancer of the stomach, currently a major disease in the Far East, relates to distinct, specific nutritional elements such as excessive salt intake. For these cancers, information is available on possible initiating genotoxic factors, promoting elements, and prophylactic agents. In general, the typical diet in the United States contains low levels of the potent carcinogenic agents, and heterocyclic amines, formed during the cooking of meats, provides only about half the potent appropriate fiber intake, and is high in calories. About twice as many calories as would be desirable come from fat, certain kinds of which enhance the development of cancers. Other foods with functional properties, such as soy products and tea, can be beneficial. To achieve reduction in risk of certain cancers, diet must be optimized, primarily to reduce caloric intake and the fat component. The latter should be 20% or less of total caloric intake and fiber should be increased to 25-35 g per day for adults. To achieve these goals, a diet should be designed around adequate fiber intake from grains, especially cereals, vegetables, legumes and fruits, which thereby reduces both calorie and fat intake. Such dietary improvements will not only reduce cancer and other chronic disease risks, but will contribute to a healthy life to an advanced age.

TOXICOLOGICAL SCIENCES, 1999, Vol 52, Iss 2, Suppl S, pp 72-86


15. Red meat consumption linked to digestive system cancers

A recent study confirms the findings of the United States Department of Agriculture, the UK Committee on the Medical Aspects of Food and Nutrition Policy and others: red meat consumption is linked to colorectal, stomach and pancreatic cancers, but not to cancers of the breast and thyroid or lymphatic system. In the study, individuals with confirmed abnormal growths (neoplasms) were asked about their red meat consumption. Information was also gathered from a control group of 7,990 patients hospitalized for "acute, non-neoplastic conditions unrelated to long-term modifications in diet." The odds ratios for the highest intake of red meat (seven or more times per week) compared with the lowest (three or fewer times per week) were 1.6 for stomach, 1.9 for colon, 1.7 for rectal, 1.6 for pancreatic, 1.6 for bladder, 1.2 for breast, 1.5 for endometrial and 1.3 for ovarian cancer. The data also showed that cancers of the oral cavity, pharynx, esophagus, liver, gallbladder, larynx, kidney, thyroid, prostate, Hodgkin's disease, non-Hodgkin's lymphomas and multiple myeloma do not appear to be associated with red meat consumption. All the studies support the conclusion that red meat consumption is an important factor in the nutritional causes of human cancer.

Int J Cancer 2000;86:425-428


16. Beer may reduce heart disease risk

Drinking beer with dinner may also be healthy for your heart. Beer contains vitamin B6, which reduces homocysteine levels in blood. High levels of homocysteine have been linked to an increase in cardiovascular disease risk, so keeping homocysteine levels under control may cut heart risk. After three weeks of drinking beer, volunteers had a 30% rise in their vitamin B6 levels without any change in their homocysteine levels. Drinking red wine or Dutch gin brought only about half that increase. At the same time, homocysteine levels increased by 8% with red wine drinking and 9% with Dutch gin drinking, enough to increase the risk of cardiovascular disease by 10% to 20%. However, moderate alcohol consumption is associated with a lowered heart disease risk. Therefore, there must be another factor associated with alcohol that may compensate for this rise in homocysteine. Moderate consumption of alcohol for nine of the 12 weeks did not lead to an abnormality in any of the measures of liver function. Vitamin B6 may participate in the breakdown of homocysteine so that when vitamin B6 levels rise, homocysteine levels fall. Even independent of its effect on homocysteine, vitamin B6 appears to lower heart disease risk.

The Lancet 2000;355:1522.


17. Americans do not drink enough water

Water makes up more than 70% of the body's tissues and plays a role in nearly every body function from regulating temperature and cushioning joints to bringing oxygen to the cells and removing waste from the body. Without proper hydration, the body is exposed to a variety of health risks. A new survey of more than 2,800 people living in 14 U.S. cities reveals that most Americans fall short of recommendations to drink eight 8-ounce servings a day. Nearly three quarters of Americans are aware of the recommendation but only 34% actually drink this amount of water each day. Most people consume only about six servings of water a day and nearly 10% said they do not drink water at all. Americans also drink an average of nearly six servings a day of caffeinated beverages such as coffee and soda. These drinks can cause the body to lose water, making proper hydration even more difficult to attain. Severe dehydration can affect blood pressure, circulation, digestion and kidney function. However, on a daily basis, not getting enough water can cause fatigue, dry skin, headaches and constipation. Among those surveyed, 37% mistakenly believe that people need less water in cold weather and 49% erroneously believe the body looses less water while sleeping than while awake. Nearly one-third did not know that giving a child water instead of sugar-containing drinks such as juice or soda could help prevent childhood obesity.

Rockefeller University in New York


18. Estrogen use and early onset of Alzheimer's disease

Estrogen use seems to be protective for late onset Alzheimer's disease. However, the effects on early onset Alzheimer's disease have been unclear. For 109 women and 119 controls, a study showed that when estrogen was used, early onset Alzheimer's disease was delayed and visa versa. The study therefore suggests that estrogen use is beneficial to early onset Alzheimer's disease.

JOURNAL OF NEUROLOGY, NEUROSURGERY, AND PSYCHIATRY, 1999, Vol 67, Iss 6, pp 779-781



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