MEDICAL UPDATES

November 2000
Table Of Contents

1. Dietary antioxidant intake and the risk of intestinal cancer

   Full source: INTERNATIONAL JOURNAL OF CANCER, 2000, Vol 87, Iss 1, pp 133-140

   A study looked at the protective effect of antioxidants and intestinal cancer in 567 individuals. Vitamin C reduced all types of gastric cancer in a significant dose-response manner, with risk reductions between 40% and 60%. beta-carotene was also strongly and negatively associated with risk, particularly with the intestinal type. The associations with vitamin E were less clear. The highest intake of all three antioxidants, compared to those with the lowest intakes was associated with a 70% lower risk of developing noncardia cancer. The results suggest that antioxidants might be especially beneficial among subjects at increased risk for gastric cancer such as smokers and those infected by H. pylori. Thus, a high intake of antioxidants, because of high consumption of fruit and vegetables, may lower the risk not only for gastric cancer of the intestine, but also for adenocarcinoma and cardia cancer.

   
   
   
2. Role of antioxidant enzymes in brain tumors

   Full source: CLINICA CHIMICA ACTA, 2000, Vol 296, Iss 1-2, pp 203-212
   
   Red blood cell (RBC) antioxidant enzymes were analyzed in 100 people with brain tumors. There was a significant decrease in RBC glutathione reductase (GRx) and superoxide dismutase (SOD) (both endogenous natural antioxidants) activity in most types of brain tumor cases. Those with acoustic neurinoma showed a significant reduction in selenium-dependent glutathione peroxidase (Se-GPx) activity. A significant increase in blood ceruloplasmin concentration was observed in those with glioma (tumor). These enzymes were also studied in 27 post-treatment cases. GRx activity returned to normal levels in these individuals. RBC SOD and blood ceruloplasmin levels showed a tendency to return to normal. Thus, a significant decrease in the antioxidant enzymes may have a role in the genesis of considerable free radical stress in those with brain tumors.
   
   

   
   
   
3. Antioxidant-rich diets improve motor learning

   Full source: BRAIN RESEARCH, 2000, Vol 866, Iss 1-2, pp 211-217

   The free radical theory of aging predicts that reactive oxygen species are involved in the decline in function associated with aging. A study showed that diets supplemented with either spinach, strawberries or blueberries, nutritional sources of antioxidants, reverse age-induced declines in beta-adrenergic receptor function in nerve cells in the cerebellum of the brain of aged rats. In addition, the spinach diet improved learning on a runway motor task, previously shown to be modulated by the neurotransmitter, norepinephrine. Motor learning is important for adaptation to changes in the environment and is thus critical for rehabilitation following stroke, spinal cord injury, and the onset of some neurodegenerative diseases. The data from the study are the first to indicate that age-related deficits in motor learning and memory can be reversed with nutritional interventions.

   
   
   
4. Alpha-lipoic acid and diabetic neuropathy

   Full source: DIABETES, 2000, Vol 49, Iss 6, pp 1006-1015

   Diabetic peripheral neuropathy (DPN) is marked by impaired nerve conduction velocity, reduced nerve blood flow (NBF), and a variety of metabolic abnormalities in the peripheral nerve that have been variously ascribed to hyperglycemia, abnormal fatty acid metabolism, ischemic hypoxia, and/or free radical stress. A study looked at the selective effects of antioxidant alpha-lipoic acid (ALA) to diabetic rats. ALA improved digital sensory, corrected endometrial nutritive NBF, increased the mitochondrial oxidative state, and enhanced the accumulation of polyol pathway intermediates without worsening myo-inositol or taurine depletion. This also implicates free radical stress as an important factor in diabetic neuropathy.

   
   
   
5. Tomato juice, vitamin E and C and type 2 diabetes

   Full source: DIABETES CARE, 2000, Vol 23, Iss 6, pp 733-738

   A study compared the effects of short-term dietary supplementation with tomato juice, vitamin E, and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein (C-RP, a risk factor for heart attack) and cell adhesion molecules in 57 type 2 diabetics (under age 75). They received either 1) tomato juice (500 ml/day), 2) vitamin E (800 U/day), 3) vitamin C (500 mg/day), or 4) continued placebo treatment for 4 weeks. Results showed that blood lycopene levels increased nearly 3-fold, and the lag time (susceptibility of LDL to oxidation) in isolated LDL oxidation by copper ions increased by 42% during supplementation with tomato juice. The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E (54%). Blood C-RP levels decreased significantly (-49%)in those who received vitamin E. Circulating levels of cell adhesion molecules and blood glucose did not change significantly during the study. The study indicates that consumption of commercial tomato juice increases blood lycopene levels and the resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E, which also decreases blood levels of C-RP in diabetics. The findings may help reduce the risk of heart attacks in diabetics.

   
   
   
6. Green tea, grape juice, and colon cancer

   Full source: BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2000, Vol 23, Iss 6, pp 695-699

   A study reported the effects of tea and juice on the activity of the intestines. Green tea strongly inhibited the E. coli-expressed mouse intestinal phenol sulfotransferases (P-STs) activity in vitro. The active component of green tea, (-)-Epigallocatechin gallate (EGCG), was found to be the most potent inhibitor among the catechins tested. (-)EGCG also inhibited the P-ST activity of the human colon cancer cells. Among fruit juices examined (apple, grape, grapefruit and orange), grape juice exhibited the most potent inhibitory action on the P-ST activity of mouse intestines and human colon cancer cells. The inhibitory activity of grape juice was located mainly in the skin and seeds. Flavonols, such as quercetin and kaempferol, inhibited the P-ST activity at low concentrations. The results suggest the possible inhibition of P-ST activity in human intestines by green tea or grape juice.
   
   

   
   
   
   
7. Supplements and exercise in the elderly

   Full source: AMERICAN JOURNAL OF PUBLIC HEALTH, 2000, Vol 90, Iss 6, pp 947-954

   A study determined the effect of enriched foods and all-around physical exercise on bone and body composition in frail elderly persons (average age 78). Foods were enriched with multiple micronutrients. Exercises focused on strength, endurance, coordination, and flexibility. Results showed that exercise preserved lean mass. Groups receiving enriched food had slightly increased bone mineral density, bone mass, and bone calcium compared with groups receiving nonenriched foods, in whom small decreases were found. Thus, foods containing a physiologic dose of micronutrients slightly increased bone density, mass, and calcium, whereas moderately intense exercise preserved lean body mass in frail elderly persons.

   
   
   
   
8. Alpha-lipoic acid lowers blood pressure

   Full source: JOURNAL OF HYPERTENSION, 2000, Vol 18, Iss 5, pp 567-573

   In hypertensive rats (HRs), free calcium and blood pressure is increased. It has been shown that N-acetyl cysteine (NAC) normalizes elevated blood pressure in HRs by normalizing membrane calcium channels and cytosolic free calcium. A study investigated whether a dietary supplementation of an alpha-lipoic acid (an endogenous fatty acid known to increase tissue cysteine and glutathione) can lower blood pressure and normalize associated biochemical and pathological changes in HRs. The control group and the HR control group were given a normal diet. The alpha-lipoic acid group was given a diet supplemented with lipoic acid (500 mg/kg feed). Results after 9 weeks showed systolic blood pressure, platelet calcium, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in HR controls as compared with control group and the alpha-lipoic acid group. HR controls also showed smooth muscle cell hyperplasia (enlargement) in the small arteries and arterioles of the kidneys. Thus, dietary alpha-lipoic acid supplementation lowered the systolic blood pressure, cytosolic calcium, blood glucose and insulin levels, and tissue aldehyde conjugates, and weakened the adverse tissue changes in the kidneys.

   
   
   
   
9. Ginkgo biloba protects and rescues brain cells

   Full source: JOURNAL OF NEUROCHEMISTRY, 2000, Vol 74, Iss 6, pp 2268-2277

   An excess of the free radical nitric oxide (NO) is viewed as a negative factor involved in various central nervous system (CNS) disorders. Numerous studies have shown that ginkgo is a NO scavenger with neuroprotective properties. A study investigated the effect of ginkgo constituents against toxicity induced by NO generators on cells of the hippocampus (brain area particularly susceptible to neurodegenerative damage). Exposure of rat hippocampal cell cultures to an inducer of oxidative stress resulted in both a decrease in cell survival and an increase in free radical accumulation. These induced events were blocked by Ginkgo. Ginkgo was also able to rescue hippocampal cells preexposed to a free radical inducing chemical. Gingko was shown to block the activation of PKC artificially induced. (It is believed that protein kinase C is the receptor protein for phorbol esters. Phorbol esters are tumor-promoting compounds used in cell biological experiments as activators of protein kinase C). The data suggest that the protective and rescuing abilities of gingko are not only attributable to the antioxidant properties of its flavonoid constituents but also via their ability to inhibit NO-stimulated PKC activity.
   
   

   
   
   
   
10. Benefits of fruits and vegetables

    Full source: JOURNAL OF NUTRITION, 2000, Vol 130, Iss 6, pp 1578-1583

    A high consumption of fruits and vegetables is associated with a decreased risk of chronic diseases. Little is known about the bioavailability of constituents from vegetables and fruits and the effect of these constituents on markers for disease risk. Currently, the recommendation is to increase intake of a mix of fruits and vegetables ("five a day"). A study investigated the effect of this recommendation on blood carotenoids, vitamins and homocysteine concentrations in a 4-week period. Forty-seven men and women were given either a daily 500-g fruit and vegetable ("high") diet or a 100-g fruit and vegetable ("low") diet. The total carotenoid, vitamin C and folate concentrations of the daily high diet were 13.3 mg, 173 mg and 228.1 mu g, respectively. The daily low diet contained 2.9 mg carotenoids, 65 mg vitamin C and 131.1 mu g folate. Differences in final blood levels between the high and low group were as follows: lutein, 46%; beta-cryptoxanthin, 128%; lycopene, 22%; alpha-carotene, 121%; beta-carotene, 45%; and Vitamin C, 64%. The high group had an 11% lower final blood homocysteine and a 15% higher blood folate concentration compared with the low group. This is the first trial to show that a mix of fruits and vegetables, with moderate folate content, decreases plasma homocysteine concentrations in humans.

    
    
11. Deprenyl protects cultured nerve cells

    Full source: BIOCHEMICAL PHARMACOLOGY, 2000, Vol 59, Iss 12, pp 1589-1595

    L-Deprenyl, an MAO-B (monoamine oxidase B) inhibitor, is used for the treatment of Parkinson's disease and to delay the progression of Alzheimer's disease. L-Deprenyl also protects against nerve cell death. A study compared the anti-apoptotic efficacy of L-deprenyl against different types of substances that cause apoptosis (cell death), in three nerve cell cultures treated with okadaic acid. (Okadaic acid treatment in vivo is known to induce an Alzheimer's type of hyperphosphorylation of tau protein, formation of beta-amyloid plaques, and severe memory impairment). L-deprenyl significantly protected against the apoptotic response induced by the addition of okadaic acid in all three nerve cell cultures.

    
    
    
12. Genistein inhibits PSA expression in prostate cancer cells

    Full source: INTERNATIONAL JOURNAL OF ONCOLOGY, 2000, Vol 16, Iss 6, pp 1091-1097
    
    There is convincing evidence for the role of soy-isoflavones, particularly genistein, in the inhibition of prostate cancer cell growth. Prostate specific antigen (PSA) is a biological marker used to detect and monitor the treatment of those with prostate cancer. Previous studies have documented that isoflavones can inhibit the secretion of PSA in androgen-dependent prostate cancer cells. A study explored the effects of genistein on androgen-independent PSA activity. Prostate cancer cells were utilized which express PSA in an androgen-independent manner, to determine the effects of genistein on cell proliferation and PSA expression. The study showed that genistein inhibits cell growth similarly in two prostate cancer cell types, but has differential effects on PSA expression. Using concentrations of genistein that have been detected in the blood of humans consuming a soy-rich diet, it was found that genistein decreases messenger RNA in PSA, protein expression and secretion. Genistein inhibited cell proliferation independently of PSA signaling pathways. This provides further evidence to support the role of genistein as a chemopreventive/therapeutic agent for prostate cancer regardless of androgen responsiveness.
    
    

    
    
    
13. NAC modulates growth of human prostate cancer cells

    Full source: INTERNATIONAL JOURNAL OF ONCOLOGY, 2000, Vol 16, Iss 6, pp 1215-1219

    The effects of the N-acetylcysteine (NAC) conjugates of isothiocyanates (present in cruciferous vegetables) on tumor cell growth were analyzed in human prostate cancer cell lines LNCaP, androgen-dependent, and DU-145, androgen-independent. Exposure of the cells to NAC dissociation products at high concentrations caused cytolysis (dissolution of cells), while at lower concentrations NAC mediated a dose-dependent growth modulation, with reduction of DNA synthesis and growth rate, and induction of apoptosis in both types of prostate cancer cells. NAC decreased cells in S and G(2)M growth phases of cell cycle, blocking cells entering replicating phases. There was a significant enhancement of cells expressing the cell cycle regulator p21. The action of NAC was time-dependent, with the magnitude of inhibition increasing to 50-65% after NAC exposure for several days. The interaction of tumor cells with dissociation products of NAC, are thus proposed as the mechanism of growth regulation.

    
    
    
14. Vitamin E prevents brain cell death

    Full source: ARCHIVES OF TOXICOLOGY, 2000, Vol 74, Iss 2, pp 112-119

    Fumonisin is a fungal toxin that occurs widely in the food chain. Studies have associated it in contaminated food with human cancer of the esophagus in China and South Africa. Brain cells incubated with fumonisin caused DNA fragmentation and apoptosis. However, pre-incubation of the cells with vitamin E for 24 hours before Fumonisin significantly reduced DNA fragmentation and brain cell death.

    
    
    
15. Olive oil, lipid peroxidation and glutathione

    Full source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, Vol 1485, Iss 1, pp 36-44

    A study looked at the effect of supplementation of a high fat diet with olive oil in rabbits for 6 weeks. The atherogenic diet increased tissue lipid peroxidation and decreased the protective antioxidant effect of glutathione. However, dietary supplementation with olive oil reduced tissue lipid peroxidation by 71.6% in liver, 20.3% in brain, 84.5% in heart, 63.6% in aorta, 72% in platelets. Olive oil increased glutathione peroxidase and transferase activities in all tissues. Thus, in rabbits made hyperlipemic with a diet rich in saturated fatty acids, olive oil decreased free radical stress in the tissues.

    
    
    
16. Glutathione and longevity

    Full source: ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 2000, Vol 46, Iss 1, pp 51-56

    Glutathione, a natural endogenous antioxidant, has been shown to be a defense against xenobiotic (synthetic compound not occurring naturally) toxicity in mammals. A study exposed eels to a pesticide for 96 hours and compared levels of glutathione in relation to the degree of resistance to the pesticide. The fish that died before 96 hours of exposure were considered susceptible to the pesticide, while those dead after 96 hours and the surviving ones were called resistant. Liver glutathione (GSH) content in susceptible eels was lower than that in the control fish, while resistant eels presented GSH levels 3-fold higher than those of controls did. The results indicate that the eels that were able to synthesize glutathione in the liver due to the presence of the pesticide in the water, demonstrated a greater longevity than those who lost glutathione homeostasis.
    
    

    
    
    
    
17. NAC, glutathione induction, and epilepsy

    Full source: EPILEPSY RESEARCH, 2000, Vol 40, Iss 1, pp 33-39

    Free radical stress is thought to be an important factor in the neurological deterioration present in epilepsies, which are difficult to treat with most antiepileptic drugs. Four individuals with Unvericht-Lundborg disease (a form of epilepsy) were given high doses (6 g/day) of N-acetylcysteine (NAC), a glutathione precursor, to determine if symptoms of epilepsy would improve. The results showed that SOD was significantly lower in the red blood cells in those with epilepsy compared to controls. Therefore, NAC improved significantly and stabilized the neurological symptoms caused by free radical stress in those with Unvericht-Lundborg disease.

    
    
    
    
18. Physical activity and oxidative stress during aging

    Full source: INTERNATIONAL JOURNAL OF SPORTS MEDICINE, 2000, Vol 21, Iss 3, pp 154-157

    Physical activity and exercise have several beneficial effects for physical and psychological health in the young and aged. Exercise may reduce age-related lean body mass loss and risk for several chronic diseases including coronary artery disease, hypertension, non-insulin-dependent diabetes mellitus, anxiety, depression, functional decline, and frailty. Exercise, however, especially when performed strenuously, is associated with increased production of free radicals, able to consume endogenous antioxidants and eventually to damage biological molecules and key cellular components. Therefore, the balance between beneficial and potentially harmful effects of exercise might be of particular importance in the elderly, in which nutritional deficiencies, sedentary lifestyle, and comorbidity commonly concur to a depletion of the antioxidant reservoir of the organism and increased susceptibility to free radical stress. The full article discusses current experimental, clinical, and epidemiological knowledge regarding known associations and potential links between free radical stress and physical activity/exercise during aging. Before a final recommendation can be made with respect to the possible preventive and therapeutical role of antioxidant supplementation in aged exercising people, there is a substantial need for further studies.

    
    
    
    
    

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