Elsevier

Clinical Nutrition

Volume 24, Issue 2, April 2005, Pages 172-183
Clinical Nutrition

REVIEW
Can oxidative damage be treated nutritionally?

https://doi.org/10.1016/j.clnu.2004.10.003Get rights and content

Summary

Background & aims: Nutrition and dietary patterns have been shown to have direct impact on health of the population and of selected patient groups. The beneficial effects have been attributed to the reduction of oxidative damage caused by the normal or excessive free radical production. The papers aims at collecting evidence of successful supplementation strategies

Methods: Review of the literature reporting on antioxidant supplementation trials in the general population and critically ill patients.

Results: Antioxidant vitamin and trace element intakes have been shown to be particularly important in the prevention of cancer, cardiovascular diseases, age related ocular diseases and in aging. In animal models, targeted interventions have been associated with reduction of tissue destruction is brain and myocardium ischemia-reperfusion models. In the critically ill antioxidant supplements have resulted in reduction of organ failure and of infectious complications.

Conclusions: Antioxidant micronutrients have beneficial effects in defined models and pathologies, in the general population and in critical illness: ongoing research encourages this supportive therapeutic approach. Further research is required to determined the optimal micronutrient combinations and the doses required according to timing of intervention.

Introduction

The last 50 years have been characterised by the understanding of the impact of nutrition and dietary patterns on health.1 Oxidation of lipids, nucleic acids or proteins has been suggested to be involved in the aetiology of several chronic diseases including cancer, cardiovascular disease, cataract, age-related macular degeneration and aging in general. The “free radical theory of aging” proposed in 1957 by Harman2 has fostered a important body of research investigating the potential role of antioxidant nutrients in therapeutic or preventive strategies.3 In the critically ill patients, free radical-mediated damage has also generated a large body of research, and various antioxidant strategies have been proposed.

Until very recently, the only mean of prolonging life span in laboratory animals was to restrict their calorie intake. A trial published in 2004 using nutritional antioxidants challenges this evidence: the life span of mice-fed diets enriched with a metabolite of curcuma vs. standard diets was prolonged 11.7% (84 days) by the supplementation: similarly in another series of mice-fed standard diets, the addition of green tea extracts to drinking water resulted in a 6.4% (52 days) prolongation of life span.4 Both antioxidant agents are know for their atherosclerosis preventing properties, pathology which is irrelevant in wild-type rodents, but is a killer in humans: supplementation with these agents can therefore be expected to be even more effective in humans. Beyond these specific results, these animal data demonstrate that AOX intervention strategies have a significant impact on a series of biological variables and on survival—is this form of supplementation to be considered as prevention or as a therapy?

Individuals in the Mediterranean area have been shown to present with a lower risk of several important chronic diseases, including coronary heart disease and a number of types of cancer associated with nutritional traditions, such as breast, colon, and prostate cancer. The use of large amounts of vegetables and fruits in general and cooked tomatoes, together with olive oil, appears to account for this lower risk.5 Among the nutrients that have “disease preventive” properties, vitamins and trace elements have been shown to be the most active components. Beyond micronutrients, other nutrients such glutamine may also be considered as antioxidant especially in selected critically ill patients. Overall many substances can be considered antioxidant, including some drugs, but are beyond the scope of the present review which will concentrate on vitamins and trace elements, and consider their potential “therapeutic” value in treating oxidative damage.

Section snippets

Free radicals, inflammatory response and oxidative stress

Free radicals and their deleterious effects have been extensively reviewed.6, 7, 8 Briefly, free radicals are atoms or molecules containing one or more unpaired electrons: they are unstable and strive to restore parity. The oxygen-centred radicals which are produced under normal aerobic metabolism, are also called reactive oxygen species (ROS); they are mainly produced by leukocytes and by the respiratory mitochondrial chain; they are essential for cell signalling, and for bacterial defence.

Antioxidants

Antioxidants (AOX) are substances, which inhibit or delay oxidation of a substrate while present in minute amounts.17 Endogenous AOX defences are both non-enzymatic (e.g. uric acid, glutathione, bilirubin, thiols, albumin, and nutritional factors, including vitamins and phenols) and enzymatic (e.g. the superoxide dismutases, the glutathione peroxidases=GSHPx, and catalase). In the normal subject the endogenous antioxidant defences balance the ROS production, but for the above-mentioned 1% daily

Status of the general population

An important part of the population is exposed to the risk of trace element and vitamin deficiency for multiple reasons including the changes in eating habits in Western countries, but also the lower food concentration of micronutrients caused by intensive agricultural techniques, compared to standards determined in the 1950s. Children, young women and elderly aged 65 years and up are most exposed.25 Indeed, more than 10 years ago, a French study showed of large-scale deficit in micronutrients

Intervention trials

Efforts to fight nutrient deficiencies have centred on supplemental nutrient administration and on addition of selected nutrients to the food chain in the form of food fortification.1 Supplementation and fortification has been proposed in healthy individuals, with the aim of reducing their risk of future diseases such as cardiovascular diseases, diabetes, and cancer. Nevertheless, with our increasing understanding of the genetic heterogeneity of human nutrient requirements, it is likely that

Discussion and conclusion

For all the above-mentioned reasons my answer to the question « can oxidative damage be treated nutritionally? » is yes. If one considers the cellular mechanisms, current knowledge clearly supports the role of AOX nutrients in the intracellular prevention AOX-related damage and of proximity damage propagation. AOX also appear to have defined pathology targets: some examples of AOX modulable conditions are ischemia-reperfusion, burns, renal failure, age-related ocular diseases, and some cancers.

References (72)

  • Z. He et al.

    Zinc-deficiency increases infarct size following permanent middle cerebral artery occlusion in rats

    Nutr Res

    (1997)
  • E.A. Malecki et al.

    Manganese protects against heart mitochondrial lipid peroxidation in rats fed high levels of polyunsaturated fatty acids

    J Nutr

    (1996)
  • P. Varo et al.

    Selenium intake and serum selenium in Finlandeffects of soil fertilization with selenium

    Am J Clin Nutr

    (1988)
  • S. Hercberg et al.

    “The SU.VI.MAX Study”a primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers. Supplementation on vitamines et mineraux antioxydants

    Food Chem Toxicol

    (1999)
  • J. Villar et al.

    Nutritional interventions during pregnancy for the prevention or treatment of maternal morbidity and preterm deliveryan overview of randomized controlled trials

    J Nutr

    (2003)
  • G. Bjelakovic et al.

    Antioxidant supplements for prevention of gastrointestinal cancersa systematic review and meta-analysis

    Lancet

    (2004)
  • M.S. Willis et al.

    The role of nutrition in preventing prostate cancera review of the proposed mechanism of action of various dietary substances

    Clin Chim Acta

    (2003)
  • M.M. Berger et al.

    Cutaneous zinc and copper losses in burns

    Burns

    (1992)
  • M.M. Berger et al.

    Copper, selenium, zinc and thiamine balances during continuous venovenous hemodiafiltration in critically ill patients

    Am J Clin Nutr

    (2004)
  • M.M. Berger et al.

    Relations between copper, zinc and selenium intakes and malondialdehyde excretion after major burns

    Burns

    (1995)
  • M.M. Berger et al.

    Trace element supplementation modulates pulmonary infection rates after major burnsa double blind, placebo controlled trial

    Am J Clin Nutr

    (1998)
  • M.M. Berger et al.

    Influence of early trace element and vitamin E supplements on the plasma antioxidant status after major traumaa controlled trial

    Nutr Res

    (2001)
  • B. Caballero

    Fortification, supplementation, and nutrient balance

    Eur J Clin Nutr

    (2003)
  • D. Harman

    Aginga theory based on free radical and radiation chemistry

    J Gerontol

    (1957)
  • K. Kitani et al.

    Interventions in aging and age-associated pathologies by means of nutritional approaches

    Ann NY Acad Sci

    (2004)
  • J.H. Weisburger

    Lycopene and tomato products in health promotion

    Exp Biol Med

    (2002)
  • S. Cuzzocrea et al.

    Antioxidant therapya new pharmacological approach of shock, inflammation, and ischemia/reperfusion injury

    Pharmacol Rev

    (2001)
  • C. Goodyear-Bruch et al.

    Oxidative stress in critically ill patients

    Am J Crit Care

    (2002)
  • E. Bulger et al.

    Antioxidants in critical illness

    Arch Surg

    (2001)
  • H.J. Schiller et al.

    Antioxidant therapy

    Crit Care Med

    (1993)
  • J.M.C. Gutteridge

    Free radicals in disease processes—a compilation of cause and consequence—invited review

    Free Radical Res Commun

    (1993)
  • A. Hartmann et al.

    Recommendations for conducting the in vivo alkaline Comet assay. Fourth international comet assay workshop

    Mutagenesis

    (2003)
  • H. Sakamoto et al.

    Isoprostanes—markers of ischemia reperfusion injury

    Eur J Anaesthesiol

    (2002)
  • I.Y. Kim et al.

    Inhibition of NF-kB DNA binding and nitric oxide induction in human T cells and lung adenocarcinoma cells by selenite treatment

    Proc Natl Acad Sci USA

    (1997)
  • M.M. Berger et al.

    Key vitamins and trace elements in the critically ill

  • D.V. Parke

    Nutritional antioxidants in disease preventionmechanisms of action

  • Cited by (0)

    View full text