Importance of zinc in the elderly: the ZENITH study

Abstract

The elderly are at nutritional risk as a result of multiple physiological, social, psychological, and economic factors. Physiological functions naturally decline with age, which may influence absorption and metabolism. Social and economic conditions can adversely affect dietary choices and eating patterns. However, at the same time, the nutrient needs of the elderly for certain nutrient (such as vitamins, minerals, proteins) is higher than for younger adults. This article reviews the importance of zinc (Zn) in elderly people, particularly for behavioural and mental function, micronutrient status, immune and antioxidant system, and bone metabolism.

Sponsorship:

The ZENITH Study is supported by the European Commission ‘Quality of Life and Management of Living Resources’ Fifth Framework Program, Contract No: QLK1-CT-2001-00168.

Introduction

Zinc (Zn) is essential for human health and well-being. It has a structural and functional role in a large number of macromolecules and is required for over 300 enzymic reactions. Zn ions participate in all aspects of intermediary metabolism, transmission, and regulation of the expression of genetic information, storage, synthesis, and action of peptide hormones and structural maintenance of chromatin and biomembranes. Zn is thus needed for growth and development, protein and DNA synthesis, neuro-sensory functions, cell-mediated immunity, thyroid, and bone metabolism. Long-term marginal intakes of Zn coupled with a decreased absorptive efficiency could severely compromise Zn status in older individuals. Indeed, a moderate deficiency of Zn is often observed in elderly subjects (Blumberg, 1997), even in industrialized countries. This suboptimal status might be responsible for the high incidence of infections and degenerative pathologies related to age (including diminished taste acuity, oxidative stress, altered immunity function, neurological disorders). This mini-review will present the importance of Zn in elderly for psychological functions, micronutrient status, immune and antioxidant system, and bone metabolism.

Zinc and psychological functions

About 90% of the total brain Zn is tightly bound to metalloproteins. Zn in the adult brain is located in the cerebral cortex (Frederickson et al, 2000), the ‘thinking’ part of the brain. This region includes the hippocampus, which is assumed to play a role in episodic memory and spatial ability, and the amygdala or ‘feeling’ part of the brain (Killcross, 2000). Zn is found in the presynaptic vesicles of glutamatergic neurons, which use glutamate as a transmitter. The role of Zn in these neurons is controversial but may include participation in the storage, release and uptake of glutamate, and modulation of glutamate receptors (Li et al, 2001). Zn can act as a neuromodulator or neurotransmitter (Harrison & Gibbsons, 1994). As Zn deprivation may influence brain Zn homeostasis, it is an important nutrient for the brain function (Takeda et al, 2000). Evidence from the available literature suggests that both deficiency and excess of Zn may have profound positive and negative consequences, respectively, on human behaviour. Serum Zn concentrations have been associated with impaired cognitive function in older individuals (Ortega et al, 1997). Research has shown that certain micronutrients, including Zn, are significantly depleted in depressed patients (Maes et al, 1994), and Zn depletion has also been implicated in mood disorders (Mc Loughlin & Hodge, 1990; Nowak & Szewczyk, 2002). Furthermore, older studies of human subjects reported that Zn deficient individuals have declined taste acuity which can be restored by Zn supplementation (Markovits et al, 1990); however, the literature on this topic appears contradictory (Fairweather-Tait, 1988). Zn deficiency has also been identified as a possible contributor to loss of appetite (Little et al, 1989) and anorexia (Su & Birmingham, 2002), by inhibiting the release of neuropeptide Y (NPY), which is required for receptor activation (Lewenson, 2003). Indeed, NPY regulates a wide variety of physiologic functions (Thorsell & Heilig, 2002) and it is also known to act as an orexigen (a stimulator of food intake).

Zinc and biological functions

Zn and status of other micronutrients

The balance among micronutrients within the body appears to be finely regulated and it is therefore very important, particularly in elderly, for whom deficiency in one or several micronutrients may have functional consequences on health. High intakes of Zn depress copper (Cu) absorption and decrease Cu status by stimulating the formation of metallothionein (MT). A high level of MT prevents Cu absorption/uptake into the intestine, liver, and kidney (Disilvestro & Cousins, 1983). Cu deficiency adversely affects lipid metabolism by decreasing HDL-cholesterol (Abiaka et al, 2003) and predisposes to cardiovascular abnormalities, by a mechanism which may involve free radical scavenging (Klevay et al, 1994). Moreover, Cu deficiency impairs lysyl oxidase function, an indispensable enzyme for structural integrity of vascular connective tissues (Allen & Klevay, 1978). In addition, the findings from metabolic studies and supplementation trials (Solomons, 1986; O’Brien et al, 2000) suggest an antagonist relationship between iron (Fe) and Zn, whereby Zn reduces the absorption of Fe and vice versa. Historically, the antagonism reported in literature was attributed to a competition between iron and zinc for transport by divalent metal transporter-1 (DMT1), which presents an affinity for iron and other divalent metals (Gunshin et al, 1997). But, recent studies show that Zn does not reduce Fe absorption, by virtue of the fact that the DMT1 is not implicated in the intestinal Zn absorption (Bannon et al, 2003). In further support of this argument, a family of human intestinal Zn transporters (ZIP) was recently identified, suggesting separate mechanisms for Fe and Zn absorption (Gaither & Eide, 2001).

In the case of vitamins, marginal, or low Zn status has been shown to decrease absorption of food folate, because the brushborder membrane folate conjugase, responsible for cleaving folate prior to absorption, is a Zn-dependent enzyme. Zn is necessary for the synthesis of hepatic cellular retinol-binding protein, which is essential for the intracellular transport of vitamin A in addition to its well-established extracellular transport role (Mejia, 1986). Consequently, marginal Zn intake is associated with decreased mobilization of retinol from the liver and also with a lowered concentration of transport proteins in the blood, such as albumin, prealbumin, and transferring. The literature shows also that dietary Zn deficiency may increase the nutritional requirement for vitamin E (Bunk et al, 1989), a very powerful antioxidant.

Zn and immunity

Zn plays a vital role in normal immune function. With advancing ageing, there is a progressive decline in immune responses. Changes associated with ageing may be partly related to Zn deficiency, which induce comparable impairment of the immune response (Dardenne, 2003). Several types of immune cells show decreased functionality after Zn depletion; in monocytes, overall functionality is impaired, whereas in natural killer cells, cytotoxicity is decreased, and in neutrophil granulocytes, phagocytosis is reduced (Shankar & Prasad, 1998). The normal functions of T cells are impaired by Zn depletion, but autoreactivity and alloreactivity are increased. Zn is also a major intracellular regulator of lymphocyte apoptosis in vitro and in vivo (Ibs & Rink, 2003). Secretion and function of cytokines, the basic messenger of the immune system are also adversely affected by Zn deficiency (Prasad, 2000). On the other hand, impaired immune function in elderly subjects due to Zn deficiency has been shown to be reversed by an adequate Zn supplementation (Prasad et al, 1993; Girondon et al, 1999). While beneficial effects of lower doses of Zn (<50 mg/d) on immune function have been reported, very high doses of Zn (>150 mg/d) may impair cellular immunity (Chandra, 1984).

Zn and oxidative stress

Zn has been shown to possess antioxidant activity in in vitro and in many animal and human studies (Powell, 2000; Klotz et al, 2003). Dietary Zn deficiency causes increased susceptibility to oxidative damage of membrane fractions from some tissues. Thus, increased oxidative stress may be a small, but significant, component of pathologies observed in elderly, in particular, cardiovascular diseases (Singh et al, 1998). At least two mechanisms have been elucidated: the protection of sulphhydryl groups against oxidation, and the inhibition of the production of reactive oxygen by transition metals (Bettger, 1993). Although Zn may act as a biological antioxidant, high levels of Zn could also be a pro-oxidant by eliciting a decline in erythrocyte Cu–Zn superoxide dismutase (SOD) (Abdallah & Samman, 1993).

Zn and bone metabolism

Osteoporosis is a common age-related condition, which is a major cause of morbidity and mortality in the elderly of both genders. Subclinical Zn deficiency, due to a reduced dietary intake and/or impaired intestinal absorption of Zn may be a contributory factor for age-related osteoporosis (Thomson & Keelan, 1986). For example, Zn is an essential cofactor for enzymes involved in synthesis of various bone matrix constituents (Heaney, 1986), and it plays a particularly important role in the regulation of bone deposition and resorption. Zn also plays a structural role in the bone matrix. Bone mineral is composed of hydroxyapatite crystals, which contain Zn complexed with fluoride. Zn is required for osteoblastic activity, directly by activating aminoacyl-tRNA synthetase in osteoblastic cells and stimulating cellular protein synthesis. Zn also promotes bone mineralization through its role as a cofactor of alkaline phosphatase (Yamaguchi, 1998). In vitro studies have emphasized that Zn plays a role in the inhibition of bone resorption by inhibiting osteoclast-like cell formation (Kishi & Yamaguchi, 1994). In animals, Zn deficiency has been associated with abnormalities in bone growth, bone formation, and mineralization (Eberle et al, 1999). Zn intake has been reported to be associated with low bone mass in women (Angus et al, 1988). Furthermore, reduced serum or plasma Zn concentrations have also been reported in osteoporotic women (Gur et al, 2002; Lowe et al, 2002).

Conclusion

Good nutritional status in older adults can be beneficial both to the individual as well as to society as a whole: health is improved, dependence is decreased, time required to recover from illness is reduced, and use of healthcare resources is controlled. However, multiple potential manifestations of Zn deficiency may occur in the elderly. Zn supplementation could be an interesting strategy aimed at improving physiological and cognitive functions in elderly. In this prospect, the objective of an European Commission-funded project ZENITH (Zinc effect in Nutrient/nutrient Interactions and Trends on Health and ageing) was to evaluate the effects of Zn on health indices in middle-aged and older people. The following short articles will provide more details about the project and some preliminary baseline findings in relation to Zn status and its correlations with several physiological parameters.

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Acknowledgements

The authors thank Nathalie Boirie for improving English.

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Correspondence to N Meunier.

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Guarantor: C Coudray.

Contributors: NM and CC wrote the paper; JMO, GM, AMR are the centre coordinators of the zenith study. All authors read and contributed to finalization of the manuscript.

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Meunier, N., O'Connor, J., Maiani, G. et al. Importance of zinc in the elderly: the ZENITH study. Eur J Clin Nutr 59, S1–S4 (2005). https://doi.org/10.1038/sj.ejcn.1602286

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Keywords

  • zinc
  • elderly
  • psychological and biological functions

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