Archives of Gerontology and Geriatrics 33 (2001) 243– 253 www.elsevier.com/locate/archger Prevalence of zinc deficiency and its clinical relevance among hospitalised elderly Thierry Pepersack a,*, Philippe Rotsaert a, Florence Benoit b, Dominique Willems b, Michel Fuss c, P. Bourdoux d, Jean Duchateau e a Geriatic Unit, Centre Hospitalier Uni6ersitaire Brugmann, Uni6ersite Libre de Bruxelles, ´ Place Van Gehuchten 4, 1020 Brussels, Belgium b Chemical Laboratory, Centre Hospitalier Uni6ersitaire Brugmann, Uni6ersite Libre de Bruxelles, ´ Place Van Gehuchten 4, 1020 Brussels, Belgium c Department of Internal Medicine, Centre Hospitalier Uni6ersitaire Brugmann, Uni6ersite Libre de Bruxelles, Place Van Gehuchten 4, 1020 Brussels, Belgium ´ d Laboratory of Pediatrics, Centre Hospitalier Uni6ersitaire Brugmann, Uni6ersite Libre de Bruxelles, ´ Place Van Gehuchten 4, 1020 Brussels, Belgium e Laboratory of Immunology, Centre Hospitalier Uni6ersitaire Brugmann, Uni6ersite Libre de Bruxelles, ´ Place Van Gehuchten 4, 1020 Brussels, Belgium Received 4 December 2000; received in revised form 22 June 2001; accepted 25 June 2001 Abstract Zinc is an essential trace element, and constituent of many metallo-enzymes required for normal metabolism. Age may be associated with altered metallothionein metabolism related to changes in zinc metabolism. The objectives of this study were: (i) to assess the prevalence of zinc deficiency among hospitalised elderly patients; (ii) to define the social, functional, pathological and nutritional characteristics of zinc deficient elderly hospitalised patients; and (iii) to assess the relationship between the zinc status and humoral immune function among hospitalised elderly patients. Fifty consecutive patients underwent comprehensive geriatric assessments included evaluations of the medical (index of the severity of the disease(s)), psychiatric (Geriatric depression scale (GDS)), therapeutic, social, functional (Katz’s scale), and nutritional problems (Mini Nutritional Assessment (MNA) and biochemical markers (zinc, albumin, prealbumin (PAB), cholesterol) before their discharge. Fourteen patients (28%) presented a zinc concentrations lower than 10.7 mmol/l, this value is usually considered * Corresponding author. Tel.: + 32-2-477-2386; fax: + 32-2-477-2178. E-mail address: thierry.pepersack@chu-brugmann.be (T. Pepersack). 0167-4943/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 7 - 4 9 4 3 ( 0 1 ) 0 0 1 8 6 - 8 244 T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 as the cut-off level below which a zinc deficient status is possible. Higher proportions of respiratory infections, cardiac failure, and depression were observed among zinc deficient patients as compared with the group of patients with normal zinc status. The other parameters of comprehensive geriatric assessment did not allow to discriminate the zinc deficient patients. The only slight differences (which remained unsignificant) concerned the prealbumin levels which tended to be higher in the group of patients presenting normal zinc status than in the group with poor zinc status (0.208 9 0.062 versus 0.171 9 0.068 g/l respectively, P=0.06), and the IgG2 levels which tended to be lower in the group of patients with normal zinc status than in the group presenting poor zinc status (2.77 91.91 versus 4.0692.56, respectively, P =0.057). A negative correlation was observed between the Zn concentrations and the IgG2 levels (Spearman R = −0.311, P=0.028). To the best of our knowledge, this is the first study presenting zinc status according to a comprehensive geriatric assessment among European hospitalised geriatric patients. We decided to perform this study to known whom of our patients needed to be supplemented with zinc administration. Considering the low energy intake of hospitalised patients (confirmed here in regards of the nutritional assessment), and the insufficient trace element density in European foods, the relevance of providing medical supplements or enriched foods to this population has to be evaluated. Although most of the current diseases may be relevant to long-term interactions between nutrition and ageing, certain states observed in the elderly, like impaired immune and cognitive functions, could still benefit from an appropriate nutritional supplementation. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Zinc; Nutrition; Comprehensive geriatric assessment; Elderly 1. Introduction Zinc is an essential trace element, and constituent of many metallo-enzymes required for normal metabolism (Endre et al., 1990; Jackson and Lowe, 1992; O’Dell, 1992). Age may be associated with altered metallothionein metabolism related to changes in zinc metabolism (Wastney et al., 1992). In the elderly, mild zinc deficiency may be associated with impaired cellular immune function (Kaplan et al., 1988). Zinc supplementation is able to correct T-lymphocyte dysfunction in zinc deficient elderly (Cossack, 1989). Several studies in the elderly indicate that they may not cover their zinc requirement (Guigoz, 1992). Epidemiological studies suggest that people with low zinc blood levels are at greater risk of developing diseases or conditions related to the ageing process, like immune function impairment (Chandra, 1990), cardiovascular disease (Salonen et al., 1982), or cancer (Strain, 1994). Zinc intake is generally reported to be particularly low in the elderly (Gibson et al., 1985; Bunker and Clayton, 1989). The aims of this study are: (i) to assess the prevalence of zinc deficiency among hospitalised elderly patients; (ii) to define the social, functional, pathological and nutritional characteristics of zinc deficient elderly hospitalised patients ; and (iv) to assess the relationship between the zinc status and humoral immune function among hospitalised elderly patients. T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 245 2. Subjects and methods 2.1. Patients Fifty patients consecutively admitted in the geriatric unit (48 beds) of our general hospital were studied prospectively between July 15 and August 28, 1998. All patients underwent a comprehensive geriatric assessments included evaluations of the medical, psychiatric, therapeutic, social, functional, and nutritional problems before their discharge. These characteristics are described in Table 1 and confirmed the ‘geriatric’ profile of the studied population (old elderly, poly-pharmacy, poly-pathology, disability, social problems, malnutrition, etc.). 2.2. Social assessment Social evaluation included determination of age, sex, home (private versus institution), marital status for each patient. Table 1 Characteristics of the patients according to the comprehensive geriatric assessment (n =50) Mean 9S.D. 83.5 6.8 Functional Katz’scale 10.4 7.8 Medical Greenfield GDS MMSE Number of therapeutic classes 10.5 5.2 20.6 4.3 1.4 0.7 2.1 2.1 Nutritional Zn (mmol/l) PAB (g/l) B.M.I. MNA (points) 12.0 0.197 21.9 19.5 2.1 0.049 6.0 3.5 % Social Age (years) Sex Females Males 86 14 Marital status Widow or celibate 26 Home Private Institution 56 44 Social, functional, medical and nutritional characteristics of the patients (n = 50). Results are expressed as the mean 9 S.D. or as the proportion of patients who fulfilled the condition. 246 T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 2.3. Functional e6aluation The assessment of activities of daily living (ADL) was made using the Katz’s scale (Katz et al., 1963). This scale involve the following items, for Katz’s scale: bathing, dressing, transfer, toileting, continence, and eating. Each task is graded in a four-level scale (1– 4 for Katz’s scale), lower levels represent the absence of dependence, and upper level, the maximal dependence for the task. 2.4. Medical e6aluation 2.4.1. E6aluation of the se6erity of the diseases The severity of the medical problems was score using a comorbidity index adapted from Greenfield et al. (1987). 2.4.2. E6aluation of the psychiatric problems The geriatric depression scale (GDS) was used in his French translation to assess the probability of a depressed state (Yesavage, 1988). The scale was completed by trained geriatricians in the presence of the patient. A score higher than five suggested the presence of depression. 2.4.3. Cogniti6e e6aluation Cognitive functions were assessed using the Mini Mental State Examination (Folstein et al., 1975). 2.4.4. E6aluation of therapeutics The number of therapies according to their classes was is collected for each patient. 2.5. Nutritional e6aluation 2.5.1. Mini nutritional assessment Nutritional assessment used the ‘mini nutritional assessment test’ (MNA) a validated tool in elderly population integrated in our geriatric assessment program (Vellas et al., 1997; Guigoz et al., 1997). The MNA test is composed of simple measurements and of rapid questions in order to be performed in less than 10 min: (1) anthropometric measurements; (2) dietary questionnaire; (3) global assessment; (4) subjective assessment (self-perception of health and nutrition). The scoring of each part allows distinguishing elderly patients with adequate nutrition to be identified as compared with those at risk of malnutrition or who are frankly malnourished. 2.5.2. Biochemical makers Plasma Zinc levels were measured at 2139 nm with a Perkin– Elmer 372 atomic absorption spectrometer according to Manning (1975). A value of zinc plasma concentrations under 10.7 mmol/l is usually considered as the cut-off level below which a zinc deficient status is possible (Expert Scientific Working Group, 1984). T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 247 Fig. 1. Histogram of plasma Zinc values among 50 hospitalised geriatric patients. Albumin determination was made with automated colorimetric method using broomcresol green, prealbumin and IgG2 by by nephelometry. Measurements of cholesterol, HDL-cholesterol and triglycerides were made by using commercial kits. LDL-cholesterol was calculated following the formula of Friedewald et al. (1972). The population was divided in two groups according to their serum PAB concentration. A serum PAB concentration higher than 170 mg/l is usually associated with a positive nitrogen balance (Mears, 1996). The patients who fulfilled this criterion are categorised into the group that is considered presenting no risk for proteino-caloric malnutrition (PCM). In the contrary, the group of patients with a PAB concentration less than 170 mg/l were considered presenting a risk of PCM. Erytrocyte folates and vitamin B127 were evaluated by chemiluminescence technology on immunoassay system (ACS 180 Chiron Diagnostics). C-reactive protein (CRP) dosages were done by a turbidimetric immunoassay (APTEC reagents). 2.6. Statistics Data were collected in a data base using the software Access from Microsoft, statistical analyses were performed with the software Statistica 5 Microsoft. Results from groups of patients were presented as means 9 S.D. Non parametric Mann – Whitney test was used to compare means between the groups. Chi square test was used to assess the differences between proportions of conditions in the groups. 248 T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 3. Results Fig. 1 shows the histogram of frequencies of zinc values in the whole population (n=50). Fourteen patients (28%) presented zinc concentrations lower than 10.7 mmol/l. Table 2 shows the characteristics of comprehensive geriatric assessment according to zinc status. No significant changes were observed in terms of social (age, sex ratio, marital status, home), functional (Katz), medical (co-morbidity index), and nutritional (albumin, prealbumin, BMI, MNA) characteristics. Table 2 Characteristics of the patients according to their plasma zinc concentrations Zn B10.7 mmol/l (n =14) Number (%) Social Age (years) Sex Females Males Marital status Widows Home Private Institution Functional Katz’s scale Medical Greenfield index GDS MMSE Number of therapeutic classes Nutritional PAB (g/l) Albumine (g/l) Triglycerides (mg%) CT (mg%) HDL Chol. (mg%) LDL Chol. (mg%) MNA (points) Immunology IgG2 (g/l) Zn \10.7 mmol/l (n =36) Number (%) Mean (S.D.) 84 (6) PB Mean (S.D.) 83 (5) 8 (57) 6 (43) 30 (83) 6 (17) 12 (86) 29 (80) 8 (57) 6 (43) 22 (61) 14 (39) 11.1 (6.9) 10.1 (4.6) NS 12 (7) 5.6 (3.4) 20 (6) 10 (5) 5.0 (3.0) 21 (7) NS NS NS 0.171 (0.068) 3.81 (0.6) 113 (39) 222 (39) 57 (13) 133 (48) 18.8 (4.8) 0.208 (0.062) 4.05 (0.6) 129 (49) 209 (49) 57 (14) 133 (33) 19.8 (4.6) 0.06 NS NS NS NS NS NS 4.06 (2.56) 2.77 (1.91) 0.057 Social, functional, medical and nutritional characteristics of the patients (n = 50). Results are expressed as the mean 9 S.D. or as the proportion of patients who fulfilled the condition. T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 249 Fig. 2. Relationship between plasma Zn concentrations and IgG2 levels (n =50). The only slight differences (which remained unsignificant) concerned the prealbumin levels which tended to be higher in the group of patients presenting normal zinc status than in the group with poor zinc status (0.2089 0.062 versus 0.1719 0.068 g/l respectively, P = 0.06), and the IgG2 levels which tended to be lower in the group of patients with normal zinc status than in the group presenting poor zinc status (2.7791.91 versus 4.0692.56 g/l respectively, P= 0.057). A negative correlation was observed between the Zn concentrations and the IgG2 levels (Spearman R= −0.311, P = 0.028) (Fig. 2). If we looked at the details of the co-morbidity index, higher proportions of congestive cardiopathy, respiratory infections, gastro-intestinal diseases and depressions were observed among the group of patients with poor zinc status as compared to those presenting normal zinc status (Table 3). 4. Discussion To the best of our knowledge, this is the first study presenting zinc status according to a comprehensive geriatric assessment among European hospitalised geriatric patients. We decided to perform this study to known whom of our patients needed to be supplemented with zinc administration. The evidence reviewed suggests that zinc deficiency is more frequent than generally perceived (Stanstead, 1995). The reasons for the lack of recognition are 250 T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 several. Evaluation of the quality and quantity of dietary zinc and concurrence with host and environmental factors that also influence zinc status is not a usual component of clinical assessment. Thus the risk of deficiency is unappreciated. Another problem is the insensitivity and difficulty of laboratory methods for assessment of zinc status. Analysis of zinc in plasma, leukocytes, and other tissues requires special instrumentation (flame atomic absorption spectroscopy). Plasma zinc, the most commonly measured index of zinc status, is insensitive and affected by circadian, meals, stress, and other factors that make interpretation difficult. In addition, plasma zinc is often in the normal range unless deficiency is severe (Stanstead, 1991). Analysis of zinc in leukocytes is difficult and not generally available as a clinical tool. We hoped that comprehensive geriatric assessment will allow us to discriminate patients with zinc deficiency. Twenty eight percent of our patients had plasma zinc concentrations B 10.7 mmol/l. This value is usually considered as the cut-off level below which a zinc deficient status is possible (Expert Scientific Working Group, 1984). It is generally recognised that plasma zinc concentration is not the optimal indicator of zinc status, partly because of the influence of factors like infections or traumatic injuries on plasma zinc levels (Gibson, 1990). Although none of the studied patients had traumatic injuries, a significant high proportion of pulmonary infections was Table 3 Pathological conditions of the 50 patients according to their plasma zinc concentrations % of pathology encountered Zn B10.7 mmol/l Zn \10.7 mmol/l PB Cardiac Arythmy Congestive cardiopathy High blood pressure Peripheral vascular disease Respiratory disease Gastro-intestinal disorder Liver disease Renal disorder Musculo-skeletal disorder Stroke Parkinson Anemia Diabetes Tumor Vision disorder Audition disorder Dementia Delirium Depression 64 36 21 43 43 36 50 7 21 50 14 0 21 7 0 29 21 21 0 50 53 25 0 36 33 19 31 8 28 39 22 6 31 19 8 25 25 25 6 33 ns ns 0.001 ns ns 0.007 0.009 ns ns ns ns ns ns ns ns ns ns ns ns 0.05 Statistical significiance of the differences in observed proportions between the groups were assessed using the 2 test. T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 251 observed among the group of patients presenting low zinc levels as compared with the group of patients with normal zinc concentrations. Although patients with poor zinc status presented a (non significant) trend of high class II immunoglobulin concentrations compared with patient with normal zinc status, this study can not precise the relationship between zinc status and pulmonary infection. In addition, changes in plasma zinc can be secondary to modifications in zinc binding or to changes in the distribution of zinc among tissues. In the present case, no significant correlation was observed between plasma zinc and albumin concentration or nutritional scores (BMI, MNA) (data not shown). The only slight differences (which remained not significant) concerned the prealbumin levels which tended to be higher in the group of patients presenting normal zinc status than in the group with poor zinc status (0.20890.062 versus 0.1719 0.068 g/l respectively, P= 0.06) suggesting that the former group tended to present a better nutritional status. Clinical relevance of zinc deficiency in elderly remains scant. In the zinc deficient group, we observed a high proportion of patients presenting congestive heart failure which are not secondary to thiamin deficiency (normal thiamin tranketolase effect), or metabolic disease (hemochromatosis, Wilson disease). Although epidemiological studies suggest that people with low zinc blood levels are at greater risk of developing cardiovascular diseases (Salonen et al., 1982; Strain, 1994), further studies are needed to confirm these data and to propose the possible underlying mechanism(s). Considering the low energy intake of hospitalised patients (confirmed here in regards of the nutritional assessment), and the insufficient trace element density in European foods (Schmuck et al., 1996), the relevance of providing medical supplements or enriched foods to this population has to be evaluated. Although most of the current diseases may be relevant to long-term interactions between nutrition and ageing, certain states observed in the elderly, like impaired immune and cognitive functions, could still benefit from an appropriate nutritional supplementation. Using vitamin and mineral containing mixtures, an enhancement of certain indices of immunocompetence was obtained in elderly subjects (Meydani, 1993; Bogden et al., 1994; Girodon et al., 1997, 1999). Chandra (1992) reported a decrease of infection-related illness in free-living, apparently healthy elderly people supplemented with physiological amounts of micronutrients. However, the potential clinical benefits of zinc supplementation in hospitalised geriatric patients remain to be studied. Unfortunately, supplementation studies are difficult to perform in the elderly population because of its heterogeneity, the confounding effects of inter-current diseases, and the lack of possibility to determine the patient at risk of zinc deficiency using comprehensive geriatric assessment. References Bogden, J.D., Bendich, A., Kemp, F.W., Bruening, K.S., Skurnick, J.H., Denny, T., Baker, H., Louria, D.B., 1994. Daily micronutrients supplements enhance delayed-hypersensitivity skin test responses in older people. Am. J. Clin. Nutr. 60, 437 – 447. 252 T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 Bunker, V.W., Clayton, B.E., 1989. Research review: studies in the nutrition of elderly people with particular reference to essential trace elements. Age Ageing 18, 422 – 429. Chandra, R.K., 1990. Micronutrients and immune functions: an overview. Ann. NY Acad. Sci. 587, 9–16. Chandra, R.K., 1992. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 340, 1124 – 1127. Cossack, Z.T., 1989. T-Lymphocyte dysfunction in the elderly associated with zinc deficiency and subnormal nucleoside phosphorylase activity: effect of zinc supplementation. Eur. J. Cancer Oncol. 25, 973 –976. Endre, L., Beck, F.W.J., Prasad, A.S., 1990. The role of zinc in human health. J. Trace Elements Exp. Med. 3, 337 –375. Expert Scientific Working Group, Federation of American Societies for Experimental Biology, 1984. Assessment of the Zinc Nutritional Status of the US Population Based on Data Collected in the Second National Health and Nutrition Examination Survey, 1976 – 1980. FASEB, Bethesda, MD. Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189 – 198. Friedewald, W.T., Levy, R.I., Fredrickson, D.S., 1972. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502. Gibson, R.S., Martinez, O.B., MacDonald, A.C., 1985. The zinc, copper and selenium status of a selected sample of non institutionalized elderly Canadian women. In: Trace Elements in Man and Animals — TEMA 5. Commonwealth Agricultural Bureaux, Aberdeen, pp. 789 – 791. Gibson, R.S., 1990. Assessment of trace elements status. In: Principles of Nutritional Assessment. Oxford University Press, Oxford, pp. 511 – 576. Girodon, F., Lombard, M., Galan, P., Brunet-Lecomte, P., Monget, A.L., Arnaud, J., Preziozi, P., Herdberg, S., 1997. Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Ann. Nutr. Metab. 41, 98 – 107. Girodon, F., Galan, P., Monget, A.L., Boutron-Ruault, M.C., Brunet-Lecomte, P., Preziozi, P., Arnaud, J., Manuguerra, J.C., Hercberg, S., and the MIN.VIT.AOX. Geriatric Network, 1999. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients. Arch. Intern. Med. 159, 748 – 754. Greenfield, S., Blanco, D.M., Elashoff, R.M., Ganz, P.A., 1987. Pattern of care related to age of breast cancer patients. J. Am. Med. Assoc. 257, 2766 – 2772. Guigoz, Y., Vellas, B., Garry, P.J., 1997. Mini Nutritional Assessment: a practical assessment tool for grading the nutritional state of elderly patients. In: Vellas, B., Guigoz, Y., Garry, P., Albarede, J. (Eds.), Facts, Research and Intervention in Geriatrics, third ed. Serdi, pp. 15 – 60. Guigoz, Y., 1992. Are the nutritional requirements of the elderly different of those of young individuals? Zinc as an example, Facts Res. Gerontol. 265 – 276. Jackson, M.J., Lowe, N.M., 1992. Physiological role of zinc. Food Chem. 43, 233 – 238. Kaplan, J., Hess, J.W., Prasad, A.S., 1988. Impaired interleukin-2 production in the elderly. J. Trace Elements Exp. Med. 1, 3–8. Katz, S., Ford, A.B., Moskowitz, R.W., Jackson, B.A., Jaffee, M.W., 1963. Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychological function. J. Am. Med. Assoc. 185, 914 –919. Manning, D.C., 1975. Aspirating small volume samples in flame atomic absorption spectroscopy. Atomic Absorption Newsletter 14, 99 – 102. Mears, E., 1996. Outcomes of continuous process improvement of nutritional care program incorporating serum prealbumin measurements. Nutrition 12, 479 – 484. Meydani, S.N., 1993. Vitamin/mineral supplementation, the aging response and risk of infection. Nutr. Res. 51, 106 –112. O’Dell, B.L., 1992. Zinc plays both structural and catalytic roles in metalloproteins. Nutr. Rev. 50, 48–50. Salonen, J.T., Alfthan, G., Pikkarainen, J., Huttunen, J.K., Puska, P., 1982. Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet 2, 175 –179. T. Pepersack et al. / Arch. Gerontol. Geriatr. 33 (2001) 243–253 253 Schmuck, A., Roussel, A.M., Arnaud, J., Ducros, V., Favier, A., Franco, A., 1996. Analyzed dietary intakes, plasma concentrations of zinc, copper, and selenium, and related antioxidant enzymes activities in hospitalized elderly women. J. Am. Coll. Nutrition 15, 462 – 468. Stanstead, H., 1991. Assessment of zinc status. J. Lab. Clin. Med. 118, 299. Stanstead, H., 1995. Is zinc deficiency a public health problem? Nutrition 11, 87 – 92. Strain, J.J., 1994. Putative role of dietary trace elements in coronary heart disease and cancer. Biomed. Sci. 51, 241 – 251. Vellas, B., Garry, P.J., Albarede, J.L., 1997. Nutritional assessment as part of the geriatric evaluation: the mini nutritional assessment. In: Vellas, B., Guigoz, Y., Garry, P., Albarede, J. (Eds.), Facts, Research and Intervention in Geriatrics, third ed. Serdi, pp. 11 – 13. Wastney, M.E., Ahmed, S., Henkin, R.I., 1992. Changes in regulation of human zinc metabolism with age. Am. J. Physiol. 263, R1162 – R1168. Yesavage, J.A., 1988. Geriatric depression scale. Psychopharmacol. Bull. 24, 709 – 711.