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Life Extension Magazine

LE Magazine April 2002


Studies from throughout the world that can help you live longer

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April 2002 Table of Contents

  1. Effect of antioxidants on metabolism of the eye and brain
  2. GH replacement therapy and VLDL cholesterol
  3. DHEAS decreases overactivity of immune system
  4. Grape seed extract weakens development of atherosclerosis
  5. Selenium, vitamin E and defense against viruses
  6. The IGF-I response to very low GH doses in human aging

1. High-dose vitamin E supplementation in diabetics

This study sought to determine the effectiveness of vitamin E treatment in normalizing blood flow of the retina and kidney function in patients with less than 10 years of type 1 diabetes. This eight-month trial evaluated 36 type 1 diabetics and nine nondiabetics. They were given 1,800 IU vitamin E/day or placebo. Before treatment, diabetic patient baseline retinal blood flow (29.1 pixel(2)/s) was significantly decreased compared with that of nondiabetic subjects (35.2 pixel(2)/s). After vitamin E treatment, diabetic patient retinal blood flow (34.5 pixel(2)/s) was significantly increased and was comparable with that of nondiabetic subjects. In addition, vitamin E treatment significantly normalized elevated baseline creatinine clearance in diabetic patients. Oral vitamin E treatment appears to be effective in normalizing retinal blood abnormalities and improving kidney function in type 1 diabetic patients of short disease duration without inducing a significant change in glycemic (sugar in blood) control. This suggests that vitamin E supplementation may provide an additional benefit in reducing the risks for developing diabetic retinopathy or nephropathy.

DIABETES CARE, 1999, Vol 22, Iss 8, pp 1245-1251

2. Melatonin enhances exercise-induced GH secretion

There is evidence that melatonin may play a role in modulating pituitary secretion, although the mechanisms are unclear. Growth hormone (GH) is secreted by the pituitary gland, which is located on the lower part of the brain under the hypothalamus. The hypothalamus is a part of the brain involved in the functions of the autonomic nervous system, and in endocrine mechanisms, and it appears to play a role in neural mechanisms underlying moods and motivational states. This study examined the effects of a single dose of oral melatonin (5 mg) on exercise-induced GH secretion. Seven healthy males undertook an initial period of graded bicycle ergometric exercise to determine maximum workload and oxygen uptake (VO2max). They were subsequently studied on two further occasions, receiving either melatonin or placebo at the onset of each study. Bicycle exercise was performed for eight min at a workload corresponding to 70% of that achieved at VO2max. Serum GH and IGF-binding protein-1 (IGFBP-1) concentration was measured at 15-min intervals from the onset of the study until 120 min after exercise. Blood was also sampled for the measurement of blood glucose, insulin, non-esterified fatty acids, IGFBP-3, melatonin and vasopressin concentration. The results showed an exercise-induced increase in GH concentration following melatonin that was greater compared with placebo, as assessed by both area under the curve and peak increase in GH levels. The peak increase in IGFBP-1 levels after exercise was also significantly greater following melatonin compared with placebo but did not quite reach levels of significance as measured on a graph by area under the curve. Since exercise-induced GH secretion is thought to be caused indirectly through a hypothalamic pathway, it seems likely that melatonin facilitates GH secretion at a hypothalamic level.

EUROPEAN JOURNAL OF ENDROCRINOLOGY, 1999, Vol 141, Iss 1, pp 22-26

3. Acetyl-L-carnitine and the effects of aging

This study looked at the effect of aging and acute treatment with acetyl-L-carnitine on the pyruvate transport and oxidation in the mitochondria (cellular organelles which provide energy) of rat heart cells. The activity of the pyruvate carrier, as well as the rates of pyruvate-supported respiration, were both depressed (around 40%) in heart mitochondria from aged rats, the major decrease occurring during the second year of life. However, administration of acetyl-L-carnitine to the aged rats almost completely restored the rates of these metabolic functions to the level of young control rats. This effect of acetyl-L-carnitine was not due to changes in the content of pyruvate carrier molecules. The heart mitochondrial content of cardiolipin, which is an essential phospholipid necessary for mitochondrial substrate (substance which is acted upon by an enzyme) transport, was markedly reduced (approximately 40%) in aged rats. Again, treatment of aged rats with acetyl-L-carnitine reversed the age-associated decline in cardiolipin content. It is suggested that acetyl-L-carnitine reverses the age-related decrement in the mitochondrial pyruvate metabolism by restoring the normal cardiolipin content.

FEBS LETTERS, 1999, Vol 454, Iss 3, pp 207-209

4. DHEA suppresses elevated liver glucose activities

The effect of dehydroepiandrosterone (DHEA) on the liver and muscle glucose metabolizing enzymes and on blood glucose were investigated in insulin-resistant diabetic mice. The results were compared with those after troglitazone administration under the same conditions. Dietary administration of DHEA and that of troglitazone for 15 days to respective groups of five mice each significantly decreased blood glucose. Because androstenedione, a DHEA metabolite, barely affected either of these enzyme activities or blood glucose in diabetic mice, the actions of DHEA, which are similar to those of troglitazone, are presumed to be caused by DHEA itself. DHEA is considered a modulating agent for the activities of liver enzymes that produce glucose in diabetic mice.

DIABETES, 1999, Vol 48, Iss 8, pp 1579-1585

5. Antioxidant role of alpha-lipoic acid in lead toxicity

The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. This study investigated the efficacy of lipoic acid (LA) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed hamster ovary cells (HOC). LA's ability to decrease lead levels in the blood and tissues of lead-treated rats was also examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione (endogenous antioxidant) levels and reducing malondialdehyde levels in the lead-exposed cells and animals. This indicated a strong antioxidant shift on lead-induced free radicals. Administration of LA to cultures of HOC cells significantly increased cell survival that was inhibited by lead treatment in a concentration-dependent manner. However, administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Therefore, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent.

FREE RADICAL BIOLOGY AND MEDICINE, 1999, Vol 27, Iss 1-2, pp 75-81

6. The challenge of invasive fungal infection

Systemic fungal infections cause almost 25% of the infection-related deaths in leukemia patients. Particularly those with prolonged neutropenia (decrease in immune cells) are at risk, but any disease carried by fungi also show up in critically ill intensive care patients and in individuals who are treated for solid tumors and AIDS, or who received an organ transplant. The spread of AIDS and the more aggressive cytotoxic chemotherapy in combination with an improved management of hemorrhages and bacterial infections in leukemia and other cancer patients facilitated the occurrence of these invasive fungal infections. These life-threatening complications remain both difficult to diagnose and to treat and therefore carry a poor prognosis. For many years, the only realistic option to treat systemic infections was amphotericin B, whose administration was known to be associated with numerous adverse effects. Now less toxic formulations of amphotericin have become available for clinical use, as well as several new triazoles that appear to provide an effective and less toxic alternative for the treatment of certain fungal infections.

CHEMOTHERAPY, 1999, Vol 45, Suppl. 1, pp 1-14

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