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LE Magazine November 1997

Weight and Chitosan

Tanaka Y Tanioka S Tanaka M Tanigawa T Kitamura Y Minami S, Okamoto Y Miyashita M Nanno M
Biomaterials (1997 Apr) 18(8):591-5

Chitin and chitosan were administered orally and parenterally into mice and their toxicity was investigated. When 5 mg of chitin were injected intraperitoneally every 2 weeks over a 12-week period, the mice were apparently normal, but histologically, many macrophages with hyperplasia were observed in the mesenterium and foreign-body giant-cell-type polykaryocytes were observed in the spleen. The polykaryocytes were also observed in the spleen of the mice injected subcutaneously with 5 mg of chitin, but no other changes were observed. When 5 mg of chitosan were injected intraperitoneally, the body weights of the mice decreased significantly and inactivity was observed in the fifth week. Histologically, many macrophages with hyperplasia were observed in the mesenterium. Subcutaneous injection of 5 mg of chitosan did not evoke the general and cellular abnormalities. Oral administration of 5% chitosan via a casein diet caused mouse body weights to decrease and also decreased the number of Bifidobacterium and Lactobacillus in normal flora of the intestinal tract. These results indicate that special care should be taken in the clinical use of chitin and chitosan over a long time period.

DHEA's Effects on Weight

Coleman DL Schwizer RW Leiter EH
Diabetes (1984 Jan) 33(1):26-32

Dehydroepiandrosterone (DHEA) was fed at 0.1-0.4% in the diet to genetically diabetic (db/db) or obese (ob/ob) C57BL/KsJ (BL/Ks) or C57BL/6J (BL/6) mice. Treatment of BL/Ks-db/db or ob/ob mice with 0.4% DHEA prevented hyperglycemia, islet atrophy, and severe diabetes associated with this inbred background, but did not affect weight gain and food consumption. Homozygous obese (ob) or diabetes (db) mice on the BL/6 background were more sensitive to DHEA, and the mild, transient hyperglycemia associated with ob or db gene expression on the BL/6 inbred background could be prevented by 0.1% DHEA. Both body weight and food consumption were decreased in BL/6 mutants maintained on 0.1% DHEA whereas this effect was not seen in BL/Ks mutants fed up to 0.4% DHEA. Early therapy with 0.4% DHEA, initiated at 2 wk of age, prevented the development of most diabetes symptoms and decreased the rate of weight gain in pups of all genotypes. In addition to therapeutic effects on both obese mutants, DHEA effected significant changes in an aging study using normal BL/6 female mice. Four weeks of DHEA treatment initiated at 2 years of age improved glucose tolerance and at the same time reduced plasma insulin to a "younger" level. This suggests that DHEA may act in insulin-resistant mutant mice and in aging normal mice to increase the sensitivity to insulin.

Anti-Obesity Properties of DHEA

Coleman DL
Prog Clin Biol Res (1988) 265:161-75

Dehydroepiandrosterone (DHEA) fed at 0.4%, and its metabolites, 3 alpha-hydroxyetiocholanolone (alpha-ET) and 3 beta- hydroxyetiocholanolone (beta-ET), fed at 0.1%, had marked anti- hyperglycemic and anti-obesity properties in mutant mice with single gene obesity mutations (diabetes, db; obese, ob; viable yellow, Avy). The therapeutic effects differed depending on the mutation as well as the inbred background on which the mutation was maintained. These steroids prevented onset of hyperglycemia and reduced the rate of weight gain in C57BL/6J-db/db and ob/ob mice, whereas in C57BL/KsJ- db/db mice, only hyperglycemia was prevented. The viable yellow (Avy) mutant, exhibiting a more slowly developing obesity condition, responded to all steroids with a marked decrease in rate of weight gain associated with decreased plasma insulin concentrations. Steroid treatment of most mouse mutants was associated with normal or increased food intake, a feature that suggests a decrease in metabolic efficiency. In order to assess any potential energy wastage by steroid stimulation of futile cycles we looked at the rates of lipogenesis, gluconeogenesis and oxygen consumption in steroid- treated normal and mutant mice. With the possible exception of the rate of gluconeogenesis that in obesity mutants was consistently reduced to normal by treatment, no metabolic changes were of sufficient magnitude to account for the marked decrease in metabolic efficiency. All treatments potentiated the action of insulin. This potentiation may change the hormonal balance such that minor changes in the rates of many metabolic pathways may interact to produce a large decrease in metabolic efficiency.

Dietary Soy Protein

Forsythe WA 3rd
J Nutr (1995 Mar) 125(3 Suppl):619S-623S

The effects of dietary protein on plasma cholesterol concentrations are well documented: animal proteins (casein) are hypercholesterolemic compared with plant proteins (soy protein). Although this effect of protein source on plasma cholesterol has been shown in many species, the mechanism is not completely understood. This paper reviews the relationship between dietary protein source and plasma thyroxine concentration. The basic premise is that feeding soy protein lowers plasma cholesterol concentration by causing an increase in plasma thyroxine concentrations. The metabolic changes involving cholesterol that occur when soy protein is fed are discussed. These changes are consistent with changes induced by elevating thyroxine. Data are presented from animal studies showing that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Furthermore, this elevation in plasma thyroxine concentrations precedes the change in plasma cholesterol concentrations: a necessary requirement for hypothesizing a causative effect. Possible mechanisms as to how a dietary protein source affects plasma thyroxine are also presented.

DHEA And Lipids

Bednarek-Tupikowska G Milewicz A Kossowska B Bohdanowicz-Pawlak A Sciborski R
Gynecol Endocrinol (1995 Mar) 9(1):23-8

The authors estimated the influence of dehydroepiandrosterone (DHEA) administration, a potential antiatherogenic agent, on serum lipids, sex hormones and insulin levels in male rabbits fed on an atherogenic diet. They concluded that (1) DHEA administration has an unfavorable impact on the serum lipid profile; (2) an atherogenic diet causes insulin resistance; (3) the glucose and insulin levels are not related to DHEA in normally fed rabbits and in rabbits with hyperlipoproteinemia; (4) an atherogenic diet causes a slight increase of estradiol concentration; (5) DHEA treatment has no significant effect on testosterone and estradiol concentrations in both normally fed rabbits and those on an atherogenic diet; (6) DHEA administration has an anti-obesity effect.

Chromium Increases Insulin Internalization

Evans GW Bowman TD
J Inorg Biochem (1992 Jun) 46(4):243-50

The effects of chromium chloride, chromium nicotinate, and chromium picolinate on insulin internalization in cultured rat skeletal muscle cells was examined. Insulin internalization was markedly increased in cells cultured in a medium that contained chromium picolinate and the increased internalization rate was accompanied by a marked increase in the uptake of both glucose and leucine. The effect was specific for chromium picolinate since neither zinc picolinate nor any of the other forms of chromium tested was effective. The increased insulin internalization rate may result from an increase in membrane fluidity since chromium picolinate and to a lesser extent, chromium nicotinate, increased the membrane fluidity of synthetic liposomal membranes.

Longevity Effect of Chromium Picolinate

McCarty MF
Med Hypotheses (1994 Oct) 43(4):253-65

The first rodent longevity study with the insulin-sensitizing nutrient chromium picolinate has reported a dramatic increase in both median and maximal lifespan. Although the observed moderate reductions in serum glucose imply a decreased rate of tissue glycation reactions, it is unlikely that this alone can account for the substantial impact on lifespan; an effect on central neurohormonal regulation can reasonably be suspected. Recent studies highlight the physiological role of insulin as a modulator of brain function. I postulate that aging is associated with a reduction of effective insulin activity in the brain, and this contributes to age- related alterations of hypothalamic functions that result in an 'older' neurohormonal milieu; consistent with this possibility, diabetes leads to changes of hypothalamic regulation analogous to those seen in normal aging. Conversely, promoting brain insulin activity with chromium picolinate may help to maintain the hypothalamus in a more functionally youthful state; increased hypothalamic catecholamine activity, sensitization of insulin- responsive central mechanisms regulating appetite and thermogenesis, and perhaps trophic effects on brain neurons may play a role in this regard. Since both the pineal gland and thymus are dependent on insulin activity, chromium may aid their function as well. Thus, the longevity effect of chromium picolinate may depend primarily on delay or reversal of various age-related changes in the body's hormonal and neural milieu. A more general strategy of hypothalamic 'rejuvenation' is proposed for extending healthful lifespan.

Deprenyl Prevents Protein Oxidation

Rodriguez-Gomez JA, Venero JL, Vizuete ML, Cano J
Brain Res Mol Brain Res 1997 Jun;46(1-2):31-8

Chronic treatment of aged rats with deprenyl prevents age-induced protein oxidation in substantia nigra and protects tyrosine hydroxylase (TH) enzyme against inactivation [11]. With these precedents, we treated adult rats with deprenyl for 3 weeks in order to get further insight in the mechanism by which deprenyl exerts such actions. After completing the treatment, dopamine (DA) levels markedly increased in both striatum and substantia nigra while levels of the acid DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), decreased in the two brain areas, thus proving MAO-inhibiting properties of the treatment. We then studied the cellular expression of TH mRNA by in situ hybridization. Following treatment with deprenyl, levels of TH mRNA were significantly higher in individual dopaminergic nigral cell bodies than in those of control rats (+74%). Western blotting analysis of TH enzyme amount revealed a positive effect of the treatment in both the terminal field (+44%) and the cell body region (+31%). This correlation between TH mRNA and amount was also extended to TH enzyme activity in the two brain areas studied, which significantly increased in striatum (+57%) and substantia nigra (+35%) following deprenyl treatment. Taken together, our results clearly suggest a TH- inducing effect of deprenyl in the dopaminergic nigrostriatal system, which seems to be independent of its protective action against oxidative stress described previously. These results expand our knowledge about the beneficial effect of deprenyl in the therapy of Parkinson's disease.

Deprenyl And 'Excess Mortality'

Riggs JE
Clin Neuropharmacol 1997 Jun;20(3):276-8

Compared with the findings for an age-matched group not taking deprenyl, a higher risk of mortality in Parkinson's disease patients taking deprenyl has recently been reported. Since a biological basis for this observation was not apparent, an epidemiological explanation was sought. Expected mortality over a 6-year period in four hypothetical age-matched groups was determined. Although groups were age matched, ages of individuals within the groups varied. Variation of individual ages within each group, without affecting the age-match comparability, produced a marked variation in expected group mortality. Mortality comparisons between age-matched groups can be invalid. This epidemiological trap might account for the recent unexplained high mortality observed in a group of Parkinson's disease patients taking deprenyl.

Vitamin E and Immunity

Meydani SN, Meydani M, Blumberg JB, Leka LS, Siber G, Loszewski R, Thompson C, Pedrosa MC, Diamond RD, Stollar BD
JAMA (1997 May 7) 277(17):1380-6

OBJECTIVE: To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell- mediated immunity in healthy elderly subjects.

DESIGN: Randomized, double-blind, placebo-controlled intervention study.

SETTING AND PARTICIPANTS: A total of 88 free-living, healthy subjects at least 65 years of age.

INTERVENTION: Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days.

MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation. RESULTS: Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and 3-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum alpha-tocopherol (vitamin E) concentration (>48.4 micromol/L [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed.

CONCLUSIONS: Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation.

Whey And Cancer

Kennedy RS Konok GP Bounous G Baruchel S Lee TD
Anticancer Res (1995 Nov-Dec) 15(6B):2643-9

Glutathione (GSH) concentration is high in most tumor cells and this may be an important factor in resistance to chemotherapy. Previous in- vitro and animal experiments have shown a differential response of tumor versus normal cells to various cysteine delivery systems. More specifically, an in-vitro assay showed that at concentrations that induce GSH synthesis in normal human cells, a specially prepared whey protein concentrate, Immunocal, caused GSH depletion and inhibition of proliferation in human breast cancer cells. On the basis of this information five patients with metastatic carcinoma of the breast, one of the pancreas and one of the liver were fed 30 grams of this whey protein concentrate daily for six months. In six patients the blood lymphocyte GSH levels were substantially above normal at the outset, reflecting high tumor GSH levels. Two patients (#1, #3) exhibited signs of tumor regression, normalization of haemoglobin and peripheral lymphocyte counts and a sustained drop of lymphocyte GSH levels towards normal. Two patients (#2, #7) showed stabilization of the tumor, increased haemoglobin levels. In three patients (#4, #5, #6,) the disease progressed with a trend toward higher lymphocyte GSH levels. These results indicate that whey protein concentrate might deplete tumor cells of GSH and render them more vulnerable to chemotherapy.