Research Database -
International Updates

Antioxidants

Issue 86

AGUILERA and co-workers, Servicio de Nefrologia, Hospitales Universitarios La Paz, Spain, describe true deficiency of vitamins E and A in dialysis patients and its relationship with clinical patterns of atherosclerosis.

Background: Atherosclerosis is an important cause of morbidity and mortality in peritoneal dialysis patients. Oxidative stress plays a role in the etiology of uremic atherosclerosis. Although antioxidant vitamins (A and E) are elevated in the blood plasma of these patients, clinical signs of vitamin deficiency are often found. Recently the importance of vitamin/carrier complexes as markers for the bioavailability of vitamins has been recognised. In this study, the bioavailability of vitamins A and E was measured as vitamin/carrier complexes, and related to atherosclerosis status in dialysis patients.

Methods: 45 patients were assessed for atherosclerosis and divided into clinical atherosclerosis scores (CAS) grades 1 to 4. Vitamins A and E and their carriers were determined.

Results: The vitamin A/carrier complex showed a statistically significant negative linear correlation with CAS and with serum iron. By univariate logistic regression analysis, significant associations between CAS and vitamin E plasma levels, vitamin E/carrier, age, and serum albumin were found.

Conclusions: These results show a vitamin/carrier complex disorder in dialysis patients that results in elevated mobilization of vitamins from pool and target cells.

Aguilera A, Bajo MA, del Peso G, Diez JJ, Codoceo R, Rebollo F, Mariano M, Selgas R, et al. True deficiency of antioxidant vitamins E and A in dialysis patients. Relationship with clinical patterns of atherosclerosis. Advances in Peritoneal Dialysis 18: 206-211, 2002.

GOLLNICK and SIEBENWIRTH, University Clinic of Dermatology and Venereology, Otto-von-Guericke University, Magdeburg, Germany, harald.gollnick@medizin.uni-magdeburg.de, have found that beta-carotene plasma levels and content in the oral mucosal epithelium is skin-type associated.

Background: Beta-carotene is one of the important antioxidants and particularly acts to protect the skin against UV radiation damage. The study was designed to measure if differences in beta-carotene in peripheral blood and in the oral mucosa are related to skin types I to IV (according to Fitzpatrick).

Methods: 174 men and women were studied for beta-carotene plasma levels. Of these, 63 healthy volunteers with skin types I – IV were studied with regard to beta-carotene plasma levels and beta-carotene content in the oral mucosa.

Results: Plasma levels were 0.1565 micromol/l in skin type I and increased through 0.2989 in type II and 0.5457 in type III to 1.221 micromol/l in type IV. A similar skin-type dependent increase in beta-carotene could be measured in the oral mucosa. Smokers had significantly lower levels of beta-carotene in plasma and oral mucosa as compared to non-smokers. Skin cancer patients also showed lower beta-carotene levels in both tissues.

Conclusions: The levels of beta-carotene in blood plasma and in oral mucosal cells are strongly associated with skin type. It is an interesting question whether these differences are genetically controlled.

Gollnick HPM, Siebenwirth C, et al. Beta-carotene plasma levels and content in oral mucosal epithelium is skin type associated. Skin Pharmacology and Applied Skin Physiology 15 (5): 360-366, Sep 2002.

SHOR-POSNER and colleagues, Department of Psychiatry, University of Miami School of Medicine, Florida, USA, review (53 references) neuroprotection in HIV-positive drug users and its implication for antioxidant therapy.

Abstract: Impaired protection of nerve cells resulting from oxidative stress has been implicated in neurodegeneration in a number of pathological conditions of the brain including both cortical and subcortical dementias. Moreover excessive oxidative stress can lead to elevated levels of certain cytokines that are thought to contribute to neuronal injury and are evident in HIV-related dementia as well as other neurodegenerative disorders. Inhibitors of oxidative damage could thus be promising therapeutic agents for preventing progressive nerve cell death and slowing the advance of neurodegenerative diseases. The potential of antioxidant therapy to provide neuroprotection is substantiated by studies demonstrating lower risk of cognitive impairment with higher plasma antioxidant levels.

Shor-Posner G, Lecusay R, Morales G, Campa A, Migue-Burbano MJ, et al. Neuroprotection in HIV positive drug users: implications for antioxidant therapy. Journal of Acquired Immune Deficiency Syndromes 31 Suppl 2:S84-S88, Oct 2002.

ZHANG et al., Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA, Shumin.Zhang@channing.harvard.edu, study the intakes of vitamins E and C, carotenoids, vitamin supplements, and the risk of Parkinson’s disease.

Background: Oxidative damage has been implicated in the pathogenesis of Parkinson’s disease (PD). Limited data suggest a reduction or no change in the risk of PD associated with high vitamin E intake.

Methods: In this prospective study, a total of 371 incident PD cases were ascertained in 2 large cohorts of men and women who completed detailed and validated semiquantitative food frequency questionnaires: the Nurses’ Health Study which comprised 76,890 women who were followed for 14 years, and the Health Professionals’ Follow-Up Study which comprised 47,331 men who were followed for 12 years.

Results: Neither intake of total vitamin E or C or use of vitamin C or E supplements or multivitamins were associated with risk of PD. However the risk of PD was significantly reduced in men and women with high intake of dietary vitamin E from foods only. Consumption of nuts was also significantly associated with a reduced risk of PD.

Conclusions: The use of vitamin supplements and high intake of carotenoids does not seem to reduce the risk of PD. The reduction in risk of Parkinson’s disease associated with high vitamin E from foods suggest that other constituents of these foods may have a protective effect, or that moderate amounts of vitamin E may reduce the risk of PD but the benefit is lost with higher intakes.

Zhang SM, Hernan MA, Chen H, Spiegelman D, Willett WC, Ascherio A, et al. Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk. Neurology 59 (8): 1161-1169, Oct 2002.

Comment: The above two studies regarding the potential role of antioxidants in the involvement of neurodegenerative disorders are potentially hugely important both to the prevention and possibly treatment of two currently devastating and fairly intractable conditions – HIV and Parkinson’s Disease. It is conceivable that antioxidant therapy could also be helpful for another fatal condition – motor neurone disease; there is a considerable interest in this research topic, as evidenced by a short search of google.com with the key words: antioxidants and motor neurone disease.

Issue 65

FERRANDEZ and colleagues, Department of Animal Physiology, Faculty of Biological Sciences, Complutense University of Madrid, Spain studied, in vitro, the changes in the effects of several antioxidants on natural killer (NK) cell activity that occur with ageing.
Methods: The following antioxidants were investigated: thiazolidine-4-carboxylic acid (thioproline); N-acetylcysteine (NAC); ascorbic acid (AA); and alpha-tocopherol (vitamin E, VE). NK cell activity of mononuclear cells from axillary nodes, spleen and thymus and peritoneal leukocytes of BALB/c male mice was assessed in a nonradioactive cytotoxic assay. Cells from young (8 weeks), adult (24 weeks), mature (48 weeks) and old (72 weeks) mice were studied. Cells from the murine lymphoma YAC-1 were used as target cells, and a ratio of effector: target cells of 10:1 was used. The concentrations of antioxidants used were: thioproline (1 mM), NAC (1 mM), AA (5 microM) and VE (5 microM). These concentrations had been found to induce a maximum effect in previous dose-response studies.
Results: In general, the antioxidants examined enhanced NK activity at all ages studied. Stimulation was higher with thioproline and NAS than with AA and VE. The effects were similar for the three lymphoid organs and the peritoneum.
Conclusion: The observed stimulation of NK cell activity by antioxidants is an important favourable response, especially in older mice, in which age results in a decrease in NK function and hence a higher
incidence of cancers.
Ferrandez MD et al. Effects in vitro of several antioxidants on the natural killer cell function of aging mice. Experimental Gerontology 34 (5): 675-85. Aug 1999.

MOLINA ARJONA and colleagues, Servicio de Neurologia, Hospital 12 de Octubre, Madrid, Spain investigated the possible relationship of several serum pro-oxidant and antioxidant substances to the risk for Parkinson’s disease.
Background: Studies have suggested a role of ‘oxidative stress’ (increased production of pro-oxidants, deficiencies of antioxidants, or both) in the pathogenesis of Parkinson’s disease.
Methods: The researchers assessed the serum levels of iron, ferritin, transferrin, ceruloplasmine, vitamin A, alpha-carotene, beta-carotene and alpha-tocopherol in 28 patients with Parkinson’s disease and 85 matched controls. All subjects were recruited from a population study.
Results: No values of pro-oxidant or antioxidant substances measured in serum differed significantly between the two study groups, and none correlated with the age at onset of disease, duration of the disease, scores on the Unified Parkinson Disease Rating Scale, or Hoehm and Yahr staging in the Parkinson’s disease group.
Conclusion: These results confirm previous findings from classic case-
control studies, suggesting an absence of a relationship between the studied variables and the risk for Parkinson’s disease.
Molina Arjona JA et al. (Serum pro-oxidant and antioxidant factors and risk of Parkinson’s disease: population study.) Revista de Neurologia 29 (1): 12-5. Jul 1999.

Comment: The search for treatment options for Parkinson’s disease is a desperate one, due to the large numbers of people afflicted, and the increasing age of the general population. The results of this research were negative, but extremely valuable to other researchers nonetheless, to prevent the needless expenditure of time, resources and finances to repeat the same experiments. This is why it is so important for journals to publish negative, as well as positive results.

ASTLEY and colleagues, Institute of Food Research, Norwich, UK investigated the effect of daily vitamin E supplementation on the susceptibility of plasma low-density lipoprotein (LDL) and lymphocyte DNA to oxidative damage in type 1 diabetes.
Methods: In this randomized, prospective, double-blind, placebo-
controlled trial, 42 patients with type 1 diabetes and 31 age- and sex-matched controls received oral vitamin E (400 IU) daily for 8 weeks. Measurements were made of single-strand breaks of lymphocyte DNA at baseline and after hydrogen peroxide-induced stress (comet assay), and of copper-induced LDL oxidization and plasma antioxidant profiles.
Results: Plasma LDL and lymphocyte DNA were more resistant to induced oxidative change in the type 1 diabetes group than in controls. Vitamin E supplementation reduced LDL oxidizability in control subjects but not in the diabetes group. Vitamin E supplementation had no effect on oxidative DNA damage in either group. The type 1 diabetes group had a significantly poorer plasma antioxidant profile, with lower mean serum concentrations of alpha-tocopherol and most carotenoids than controls.
Conclusions: Plasma LDL and lymphocyte DNA appear to be more resistant to oxidative change in type 1 diabetic subjects than in controls. There was no evidence of oxidatively induced DNA or LDL change in type 1
diabetes. The results do not support the hypothesis of oxidative
damage in type 1 diabetes. Furthermore, a dose of vitamin E (400 IU daily) that reduced LDL oxidative susceptibility in control subjects did not do so in patients with type 1 diabetes.
Astley S et al. Vitamin E supplementation and oxidative damage to DNA and plasma LDL in type 1 diabetes. Diabetes Care 22 (10): 1626-31. Oct 1999.

Comment: Again, these results disproved the hypothesis that oxidative damage to LDL and lymphocyte DNA could be alleviated by vitamin E supplementation. The surprise result was that Plasma LDL and lymphocyte DNA were in fact more resistant to oxidative change in the diabetes groups than the controls and that vitamin E had no effect upon oxidative damage in either group.