European Journal of Clinical Nutrition (2013) 67, 1325–1327 & 2013 Macmillan Publishers Limited All rights reserved 0954-3007/13 www.nature.com/ejcn
SHORT COMMUNICATION
Determinants of fat-soluble vitamin status in patients aged 65 years and over F Granado-Lorencio1,2, I Blanco-Navarro1,2, B Pe´rez-Sacrista´n1, I Milla´n3, E Donoso-Navarro2 and RA Silvestre-Mardomingo2 In the elderly, malnutrition is highly prevalent and a major contributor to increased morbidity and mortality. We aimed to evaluate the fat-soluble vitamin status and potential determinants in patients 465 years of age. Serum vitamins A, D and E were determined by liquid chromatography in 166 patients. Gender, age, season, hospitalization, nutritional markers (albumin and cholesterol), acute-phase reactants (ferritin and C-reactive protein) and renal function (creatinine and glomerular filtrate) were assessed as potential determinants. Prevalence of vitamin deficiency was highly variable, ranging from 0 (vitamin E/cholesterol ratio) to 94% (for vitamin D in hospitalized patients). Vitamin status did not differ according to gender, but age, season, hospitalization, a poor nutritional status and impaired renal function, and the presence of acute-phase response significantly affected serum levels of vitamin A, E and D. In conclusion, in subjects 465 years both demographic and clinical factors determined the fat-soluble vitamin status. European Journal of Clinical Nutrition (2013) 67, 1325–1327; doi:10.1038/ejcn.2013.198; published online 16 October 2013 Keywords: vitamin status; clinical practice; old persons; malnutrition; hospitalized patients
INTRODUCTION In older populations, malnutrition is highly prevalent1 and a major contributor to increased morbidity and mortality, decreased function and quality of life, and increased frequency and length of hospital stay.2,3 Both acute conditions and chronic diseases may be associated with nutrient loss, increased nutritional requirements and/or malabsorption, so that patients may have compromised the immune response and a poorer prognosis. In Europe, disease-related malnutrition affects some 30 million people with a prevalence of 20–50% and entails an associated annual cost of around 170 billion euros.4 In addition, micronutrient status in the elderly, as indicated by circulating levels of vitamin A, E, C, folate, carotenoids and 25(OH)D, is heterogeneous and influenced by demographic, dietary and lifestyle factors.5,6 Nutrient intake data in Europe showed that the mean prevalence of inadequacy of micronutrients in the elderly ranged between o10 (vitamin B12 in the elderly) and 46% for vitamin D in some countries,6 although vitamin D-deficient levels were observed in up to 88% of non-institutionalized subjects.5 In Spain, a nationwide, cross-sectional, observational study (Prevalence of Hospital Malnutrition and Associated costs in Spain (PREDyCES) study) conducted on 1597 patients in 31 representative hospitals under regular clinical practice conditions showed that 23% of patients admitted to Spanish hospitals were at risk of malnutrition,7 although information regarding the vitamin status and potential determinants in this group is scarce. Within this context, we aimed to assess the nutritional status of vitamins in patients 465 years, and its relationship with demographic and nutritional factors, acute-phase reactants and renal function as potential determinants of vitamin status in this group. MATERIAL AND METHODS This is an observational study intended to assess hospital malnutrition in usual clinical practice. As part of our daily clinical assistance, we
consecutively evaluated the serum status of vitamins A, E and D in 166 subjects 465 years (76.3±7.6 years; 108 women and 58 men). To avoid the use of prescribed supplements, only blood samples corresponding to the first visit were considered and no additional inclusion criteria were applied, except age. Potential determinants of vitamin status were also retrospectively recorded, if available, including sex, age (65–75, 76–85 and 86–100 years), season (official calendar dates), hospitalized versus outpatients, nutritional markers (albumin and total cholesterol), acutephase reactants (ferritin and C-reactive protein (CRP)) and renal function (serum creatinine, estimated glomerular filtrate according to modification of diet in renal disease-4 (IDMS) formula). Serum concentrations of 25-OH-D3, retinol and a-tocopherol were determined by ultra-fast liquid chromatography.8 Serum albumin, total cholesterol, ferritin, CRP and creatinine were measured using standard methods routinely used in our lab. Clinical cutoffs to define deficiency were o30 mg/dl for retinol, o0.7 mg/dl for a-tocopherol and o2.5 for a-tocopherol/total cholesterol ratio, o50 nmol/l (420 ng/ml) for 25-OHvitamin D, o20 ng/ml for albumin ando150 mg/dl for total cholesterol. The presence of acute-phase response was considered at serum ferritin 4300 ng/ml and CRP 410 mg/l, and impaired renal function was defined at serum creatinine 41.1 mg/dl (average cutoff for men and women) and estimated glomerular filtrate o60 ml/min 1.73 m2. All data were expressed as mean and 95% confidence intervals. Statistical significance of differences was assessed using one-way analysis of variance and the prevalence of inadequate status was estimated using cross-tabs. The statistical software package SPSS release 12.0.1 (SPSS Inc., Chicago, IL, USA) was used and significance was set at Po0.5.
RESULTS Prevalence of inadequate nutritional status is shown in Table 1. For all subjects, prevalence of vitamin deficiency was highly variable ranging from 0% for a-tocopherol /cholesterol ratio to 78% for vitamin D, whereas the percentage of subjects with inadequate nutritional status, acute-phase response or impaired renal function was also variable but substantially higher in
1 Unidad de Vitaminas, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain; 2Servicio de Bioquı´mica Clı´nica, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain and 3Unidad de Bioestadı´stica, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain. Correspondence: Dr F Granado-Lorencio, Unidad de Vitaminas or Servicio de Bioquı´mica Clı´nica, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid 28222, Spain. E-mail: [email protected] or [email protected] Received 3 May 2013; revised 7 August 2013; accepted 28 August 2013; published online 16 October 2013
Fat-soluble vitamin status in the elderly F Granado-Lorencio et al
1326 Table 1.
Mean, 95% confidence intervals and prevalence of inadequate values of nutritional biomarkers in subjects 465 years Cutoff a
Markers
All subjects n
Age (years) 25-OH-vitamin D (nmol/l) Retinol (mg/dl) a-tocopherol (mg/dl) a-tocopherol/cholesterol (mg/mg) Albumin (g/dl) Total cholesterol (mg/dl) C-reactive protein (mg/l) Ferritin (ng/ml) Creatinine (mg/dl) GFR (ml/min 1.73 m2)
— o50 o30 o0.7 o2.5 o3.5 o150 410 4300 41.1 o60
166 166 166 166 139 130 139 68 106 143 140
Mean (95% CI) 76.3 37.3 63.5 1.29 7.8 3.8 171 34 287 2.2 57
(75.1, 77.5) (32.7, 41.8) (57.6, 69.3) (1.23, 1.35) (7.3, 8.2) (3.7, 3.9) (164, 178) (16, 52) (232, 342) (1.8, 2.6) (51, 63)
Hospitalized patients Prevalence (%)
n
— 78 14 7 0 23 33 49 38 34 45
64 64 64 64 62 60 62 46 54 62 63
Mean (95% CI) 75.5 25.2 73.7 1.20 8.0 3.4 152 47 445 3.8 38
Outpatients
Prevalence
n
— 94 22 8 0 43 47 67 67 62 70
102 102 102 102 77 70 77 22 52 81 77
(73.9, 77.0) (21.0, 29.3) (60.6, 86.9) (1.11, 1.28) (7.5, 8.5) (3.3, 3.6) (143, 160) (21, 72) (359, 530) (3.0, 4.5) (29, 48)
Mean (95% CI) 77.5 44.8 57.0 1.35 7.6 4.2 187 7 123 1.0 72
Prevalence
(75.7, 79.3) (38.3, 51.4)* (52.4, 61.5)** (1.27, 1.43)*** (6.9, 8.3) (4.1, 4.3)* (178, 196)* (0, 15)*** (91, 155)* (0.8, 1.2)* (68, 77)*
— 68 8 7 0 6 22 14 8 13 25
Abbreviations: CI, confidence intervals; GFR, estimated glomerular filtration rate. *Po0.001; **P ¼ 0.005; ***Po0.05). aCut-off considered to define vitamin deficiency, presence of acute-phase response and impaired renal function. Differences between hospitalized and outpatients groups (one-way analysis of variance test).
Table 2.
Mean and 95% CI of the variables measured in patients 465 years
Variable (n)
Vitamin A (retinol) (mg/dl)
Vitamin E (a-tocopherol) (mg/dl)
Vitamin E/cholesterol (mg/mg)
Vitamin D (25-OH-D3) (nmol/l)
Sex Women (108) Men (58) P-value
63 (57, 69) 65 (53, 78) NS
1.34 (1.27, 1.41) 1.20 (1.10, 1.30) 0.04
7.4 (7.1, 7.9) 8.2 (7.3, 9.2) NS
39 (33, 46) 33 (28, 40) NS
Age (years) 65–75 (88) 76–85 (52) 485 (26) P-value
67 (59, 75) 62 (51, 73) 61 (42, 80) NS
1.38 (1.30, 1.47) 1.26 (1.16, 1.36) 1.14 (1.00, 1.29) o0.019
8.0 (7.3, 8.7) 7.6 (7.1, 8.2) 7.1 (6.4, 7.9) NS
39 (34, 45) 32 (37, 38) 28 (21, 35) o0.063
Season Spring (36) Summer (28) Fall (31) Winter (71) P-value
47 (41, 54) 52 (44, 60) 42 (36, 48) 85 (75, 96) o0.001
1.26 1.22 1.29 1.35
6.5 7.1 8.5 8.2
33 51 44 32
Origin Hospitalized (64) Outpatients (103) P-value
74 (61, 87) 57 (53, 62) 0.006
1.19 (1.11, 1.29) 1.35 (1.28, 1.44) 0.011
8.0 (7.5, 8.5) 7.6 (6.9, 8.3) NS
25 (21, 29) 45 (39, 52) o0.001
Albumin (g/dl) 43.5 (100) o3.5 (30) P-value
69 (61, 77) 49 (36, 63) 0.016
1.35 (1.27, 1.41) 1.10 (0.97, 1.23) 0.002
7.6 (7.2, 8.0) 8.4 (6.8, 10.0) NS
38 (34, 42) 21 (14, 27) o0.001
Cholesterol (mg/dl) 4150 (93) o150 (46) P-value
65 (59, 71) 68 (52, 85) NS
1.42 (1.35, 1.50) 1.04 (0.95, 1.13) o0.001
7.3 (7.0, 7.7) 8.6 (7.6, 9.7) 0.006
34 (30, 38) 33 (27, 40) NS
Ferritin (ng/ml) o300 (66) 4300 (40) P-value
63 (55, 70) 78 (61, 95) NS
1.27 (1.19, 1.35) 1.23 (1.11, 1.35) NS
7.5 (6.7, 8.3) 8.6 (7.9, 9.3) 0.046
36 (31,42) 25 (20, 30) 0.005
C-reactive protein (mg/l) o10 (34) 410 (33) P-value
81 (65, 97) 77 (59, 96) NS
1.43 (1.30, 1.55) 1.19 (1.06, 1.32) 0.010
8.2 (7.3, 9.0) 8.1 (7.6, 8.7) NS
35 (28, 42) 22 (17, 27) 0.004
Creatinine (mg/dl) o1.1 (93) 41.1 (48) P-value
53 (49, 57) 89 (76, 102) o0.001
1.27 (1.20, 1.34) 1.30 (1.18, 1.41) NS
7.4 (6.9, 7.9) 8.5 (7.9, 9.1) 0.013
39 (35, 44) 33 (27, 38) NS
GFR (ml/min 1.73 m2) o60 (77) 460 (63) P-value
83 (71, 95) 53 (47, 59) o0.001
1.28 (1.18, 1.39) 1.31 (1.23, 1.40) NS
8.3 (7.7, 8.8) 7.4 (6.7, 8.1) NS
31 (26, 36) 37 (32, 41) NS
(1.12, (1.09, (1.11, (1.26, NS
1.39) 1.34) 1.47) 1.44)
(6.0, 7.1) (6.4, 7.9) (6.6, 10.5) (7.7, 8.6) 0.013
(27, 39) (37, 66) (28, 60) (27, 36) 0.009
Abbreviations: CI, confidence intervals; GFR, estimated glomerular filtration rate; NS, not significant. One-way analysis of variance. NS: Po0.05.
European Journal of Clinical Nutrition (2013) 1325 – 1327
& 2013 Macmillan Publishers Limited
Fat-soluble vitamin status in the elderly F Granado-Lorencio et al
1327 hospitalized subjects. Outpatients showed significant higher levels of vitamins E and D than hospitalized patients. Season and hospitalization affected significantly serum levels of vitamin D and A, and to a lesser extent vitamin E or the a-tocopherol/cholesterol ratio (Table 2), and a clear decreasing trend with age was observed for vitamins D, E and the a-tocopherol/cholesterol ratio. Hypoalbuminemia was associated with lower concentrations of vitamin A and D, and low serum cholesterol levels were related to a lower vitamin E and a-tocopherol/cholesterol ratio. High levels of CRP and ferritin were associated with lower levels of vitamin D and E, and an impaired renal function (high serum creatinine and low glomerular filtrate) was related to higher serum retinol levels. Consequently, in hospitalized subjects, an inadequate nutritional status and a high acute-phase response were associated with a higher prevalence of vitamins D and E deficiency (up to 97 and 15%, respectively), whereas an impaired renal diminished the prevalence of vitamin A (up to 8% using the cutoff for creatinine). DISCUSSION Aging is associated with an increasing prevalence of malnutrition, a consistent finding across all settings including communitydwelling elderly, nursing home residents and geriatric hospital patients.1 In this study, we observed a high prevalence of inadequate nutritional status and a clear decreasing trend with age for vitamins E and D. However, the prevalence of inadequacy was especially high in hospitalized patients, being even higher than the rates of malnutrition previously observed in the PREDyCES study,7 a fact probably related to the study design (that is, geographical settings, sample size, inclusion criteria and so on). Suboptimal micronutrient intake for particular vitamins (vitamins A, E and D) is common in older adults,9 although highly variable depending both on the country and the vitamin (that is, from 0% for vitamin B12 to 100% for vitamin D).5,9–11 In addition, hospitalization influences vitamin and nutritional status,6,7 and pathological conditions and their treatment can both cause malnutrition. Consistently, in hospitalized subjects, we found higher rates of both vitamin and nutritional markers inadequacy reaching values of 97% for vitamin D. The cause of malnutrition is multifactorial including diseaserelated metabolic effects, reduced dietary intake and polimedication. Unfortunately, the lack of this information in the present study constitutes a major limitation to draw more robust conclusions. In addition, nutritional biomarkers can also be influenced by many factors. As shown, an impaired renal function was related to a reduced prevalence of vitamin A deficiency in hospitalized patients, a fact possibly unrelated to diet but because of a decreased retinol clearance. Also, the higher prevalence of vitamin deficiency in hospitalized subjects was associated with inadequate levels of nutritional markers and elevated acute-phase reactants. These factors, however, do not explain the high rate of vitamin D deficiency in outpatients, so that other factors such as age, season or dietary imbalance are probably more relevant contributors in this group. In conclusion, nutritional status of fat-soluble vitamins in subjects aged 465 years is highly variable and determined by
& 2013 Macmillan Publishers Limited
age, season, hospitalization, nutritional status, inflammation and renal function. Given the high prevalence of malnutrition and its impact on patient morbidity–mortality and health-care costs, an integrated nutritional care for patients while in hospital should be placed, although this measure has not been applied either in the majority of hospitals in Europe or in Spanish hospitals.7 For hospitalized patients, what indicators of vitamin status deserve to be routinely measured and which other markers should be evaluated to interpret correctly the vitamin status of the patient remains to be defined. Owing to the current trend to reduce the hospital stay, the best approach to assess, provide nutritional support and monitor the vitamin status at preadmission, in hospital and post-discharge remains to be established and deserve additional studies.
CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS The present study was performed as part of our clinical assistance to the patients and no other public or private sources of funding were used.
REFERENCES 1 Bauer JM, Kaiser MJ, Sieber CC. Evaluation of nutritional status in older persons: nutritional screening and assessment. Curr Opin Clin Nutr Metab Care 2010; 13: 8–13. 2 Lim SL, Ong KChB, Chan YH, Loke WCh, Ferguson M, Daniels L. Malnutrition and its impact on cost of hospitalization, length of stay, readmission and 3-year mortality. Clin Nutr 2012; 31: 345–350. 3 White JV, Guenter P, Jensen G, Malone A, Schofield M. The Academy Malnutrition Work Group; the A.S.P.E.N. Malnutrition Task Force; and the A.S.P.E.N. Board of Directors. Consensus Statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: characterisitics recommended for the identification and documentation of adult malnutrition (undernutrition). J Parent Enteral Nutr 2012; 36: 275–283. 4 Ljungqvist O, de Man F. Under nutrition—a major health problem in Europe. Nutr Hosp 2009; 24: 368–370. 5 Fabian E, Bogner M, Kickinger A, Wagner K-H, Elmadfa I. Vitamin status in elderly people in relation to the use of nutritional supplements. J Nutr Health Aging 2012; 16: 206–212. 6 Hausman DB, Fischer JG, Johnson M-A. Nutrition in centenarians. Maturitas 2011; 68: 203–209. 7 A´lvarez-Herna´ndez J, Planas Vila M, Leo´n-Sanz M, Garcı´a de Lorenzo A, CelayaPe´rez S, Garcı´a-Lorda P et al. On behalf of the PREDyCES researchers. Prevalence and costs of malnutrition in hospitalized patients; the PREDyCESs Study. Nutr Hosp 2012; 27: 1049–1059. 8 Granado-Lorencio F, Herrero-Barbudo C, Blanco-Navarro I, Pe´rez-Sacrista´n B. Suitability of ultra-high performance liquid chromatography for the determination of fat-soluble nutritional status (vitamins A, E, D, and individual carotenoids. Anal Bioanal Chem 2010; 397: 1389–1393. 9 Marian M, Sacks G. Micronutrients and older adults. Nutr Clin Pract 2009; 24: 179–195. 10 Roman-Vin˜as B, Ribas Barba L, Ngo J, Gurinovic M, Novakovic R, Cavelaars A et al. Projected prevalence of inadequate nutrient intake in Europe. Ann Nutr Metab 2011; 59: 84–95. 11 Troesch B, Eggersdorfer M, Weber P. 100 years of vitamins: adequate intake in the elderly is still a matter of concern. J Nutr 2012; 142: 979–980.
European Journal of Clinical Nutrition (2013) 1325 – 1327
SHORT COMMUNICATION
Determinants of fat-soluble vitamin status in patients aged 65 years and over F Granado-Lorencio1,2, I Blanco-Navarro1,2, B Pe´rez-Sacrista´n1, I Milla´n3, E Donoso-Navarro2 and RA Silvestre-Mardomingo2 In the elderly, malnutrition is highly prevalent and a major contributor to increased morbidity and mortality. We aimed to evaluate the fat-soluble vitamin status and potential determinants in patients 465 years of age. Serum vitamins A, D and E were determined by liquid chromatography in 166 patients. Gender, age, season, hospitalization, nutritional markers (albumin and cholesterol), acute-phase reactants (ferritin and C-reactive protein) and renal function (creatinine and glomerular filtrate) were assessed as potential determinants. Prevalence of vitamin deficiency was highly variable, ranging from 0 (vitamin E/cholesterol ratio) to 94% (for vitamin D in hospitalized patients). Vitamin status did not differ according to gender, but age, season, hospitalization, a poor nutritional status and impaired renal function, and the presence of acute-phase response significantly affected serum levels of vitamin A, E and D. In conclusion, in subjects 465 years both demographic and clinical factors determined the fat-soluble vitamin status. European Journal of Clinical Nutrition (2013) 67, 1325–1327; doi:10.1038/ejcn.2013.198; published online 16 October 2013 Keywords: vitamin status; clinical practice; old persons; malnutrition; hospitalized patients
INTRODUCTION In older populations, malnutrition is highly prevalent1 and a major contributor to increased morbidity and mortality, decreased function and quality of life, and increased frequency and length of hospital stay.2,3 Both acute conditions and chronic diseases may be associated with nutrient loss, increased nutritional requirements and/or malabsorption, so that patients may have compromised the immune response and a poorer prognosis. In Europe, disease-related malnutrition affects some 30 million people with a prevalence of 20–50% and entails an associated annual cost of around 170 billion euros.4 In addition, micronutrient status in the elderly, as indicated by circulating levels of vitamin A, E, C, folate, carotenoids and 25(OH)D, is heterogeneous and influenced by demographic, dietary and lifestyle factors.5,6 Nutrient intake data in Europe showed that the mean prevalence of inadequacy of micronutrients in the elderly ranged between o10 (vitamin B12 in the elderly) and 46% for vitamin D in some countries,6 although vitamin D-deficient levels were observed in up to 88% of non-institutionalized subjects.5 In Spain, a nationwide, cross-sectional, observational study (Prevalence of Hospital Malnutrition and Associated costs in Spain (PREDyCES) study) conducted on 1597 patients in 31 representative hospitals under regular clinical practice conditions showed that 23% of patients admitted to Spanish hospitals were at risk of malnutrition,7 although information regarding the vitamin status and potential determinants in this group is scarce. Within this context, we aimed to assess the nutritional status of vitamins in patients 465 years, and its relationship with demographic and nutritional factors, acute-phase reactants and renal function as potential determinants of vitamin status in this group. MATERIAL AND METHODS This is an observational study intended to assess hospital malnutrition in usual clinical practice. As part of our daily clinical assistance, we
consecutively evaluated the serum status of vitamins A, E and D in 166 subjects 465 years (76.3±7.6 years; 108 women and 58 men). To avoid the use of prescribed supplements, only blood samples corresponding to the first visit were considered and no additional inclusion criteria were applied, except age. Potential determinants of vitamin status were also retrospectively recorded, if available, including sex, age (65–75, 76–85 and 86–100 years), season (official calendar dates), hospitalized versus outpatients, nutritional markers (albumin and total cholesterol), acutephase reactants (ferritin and C-reactive protein (CRP)) and renal function (serum creatinine, estimated glomerular filtrate according to modification of diet in renal disease-4 (IDMS) formula). Serum concentrations of 25-OH-D3, retinol and a-tocopherol were determined by ultra-fast liquid chromatography.8 Serum albumin, total cholesterol, ferritin, CRP and creatinine were measured using standard methods routinely used in our lab. Clinical cutoffs to define deficiency were o30 mg/dl for retinol, o0.7 mg/dl for a-tocopherol and o2.5 for a-tocopherol/total cholesterol ratio, o50 nmol/l (420 ng/ml) for 25-OHvitamin D, o20 ng/ml for albumin ando150 mg/dl for total cholesterol. The presence of acute-phase response was considered at serum ferritin 4300 ng/ml and CRP 410 mg/l, and impaired renal function was defined at serum creatinine 41.1 mg/dl (average cutoff for men and women) and estimated glomerular filtrate o60 ml/min 1.73 m2. All data were expressed as mean and 95% confidence intervals. Statistical significance of differences was assessed using one-way analysis of variance and the prevalence of inadequate status was estimated using cross-tabs. The statistical software package SPSS release 12.0.1 (SPSS Inc., Chicago, IL, USA) was used and significance was set at Po0.5.
RESULTS Prevalence of inadequate nutritional status is shown in Table 1. For all subjects, prevalence of vitamin deficiency was highly variable ranging from 0% for a-tocopherol /cholesterol ratio to 78% for vitamin D, whereas the percentage of subjects with inadequate nutritional status, acute-phase response or impaired renal function was also variable but substantially higher in
1 Unidad de Vitaminas, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain; 2Servicio de Bioquı´mica Clı´nica, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain and 3Unidad de Bioestadı´stica, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain. Correspondence: Dr F Granado-Lorencio, Unidad de Vitaminas or Servicio de Bioquı´mica Clı´nica, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid 28222, Spain. E-mail: [email protected] or [email protected] Received 3 May 2013; revised 7 August 2013; accepted 28 August 2013; published online 16 October 2013
Fat-soluble vitamin status in the elderly F Granado-Lorencio et al
1326 Table 1.
Mean, 95% confidence intervals and prevalence of inadequate values of nutritional biomarkers in subjects 465 years Cutoff a
Markers
All subjects n
Age (years) 25-OH-vitamin D (nmol/l) Retinol (mg/dl) a-tocopherol (mg/dl) a-tocopherol/cholesterol (mg/mg) Albumin (g/dl) Total cholesterol (mg/dl) C-reactive protein (mg/l) Ferritin (ng/ml) Creatinine (mg/dl) GFR (ml/min 1.73 m2)
— o50 o30 o0.7 o2.5 o3.5 o150 410 4300 41.1 o60
166 166 166 166 139 130 139 68 106 143 140
Mean (95% CI) 76.3 37.3 63.5 1.29 7.8 3.8 171 34 287 2.2 57
(75.1, 77.5) (32.7, 41.8) (57.6, 69.3) (1.23, 1.35) (7.3, 8.2) (3.7, 3.9) (164, 178) (16, 52) (232, 342) (1.8, 2.6) (51, 63)
Hospitalized patients Prevalence (%)
n
— 78 14 7 0 23 33 49 38 34 45
64 64 64 64 62 60 62 46 54 62 63
Mean (95% CI) 75.5 25.2 73.7 1.20 8.0 3.4 152 47 445 3.8 38
Outpatients
Prevalence
n
— 94 22 8 0 43 47 67 67 62 70
102 102 102 102 77 70 77 22 52 81 77
(73.9, 77.0) (21.0, 29.3) (60.6, 86.9) (1.11, 1.28) (7.5, 8.5) (3.3, 3.6) (143, 160) (21, 72) (359, 530) (3.0, 4.5) (29, 48)
Mean (95% CI) 77.5 44.8 57.0 1.35 7.6 4.2 187 7 123 1.0 72
Prevalence
(75.7, 79.3) (38.3, 51.4)* (52.4, 61.5)** (1.27, 1.43)*** (6.9, 8.3) (4.1, 4.3)* (178, 196)* (0, 15)*** (91, 155)* (0.8, 1.2)* (68, 77)*
— 68 8 7 0 6 22 14 8 13 25
Abbreviations: CI, confidence intervals; GFR, estimated glomerular filtration rate. *Po0.001; **P ¼ 0.005; ***Po0.05). aCut-off considered to define vitamin deficiency, presence of acute-phase response and impaired renal function. Differences between hospitalized and outpatients groups (one-way analysis of variance test).
Table 2.
Mean and 95% CI of the variables measured in patients 465 years
Variable (n)
Vitamin A (retinol) (mg/dl)
Vitamin E (a-tocopherol) (mg/dl)
Vitamin E/cholesterol (mg/mg)
Vitamin D (25-OH-D3) (nmol/l)
Sex Women (108) Men (58) P-value
63 (57, 69) 65 (53, 78) NS
1.34 (1.27, 1.41) 1.20 (1.10, 1.30) 0.04
7.4 (7.1, 7.9) 8.2 (7.3, 9.2) NS
39 (33, 46) 33 (28, 40) NS
Age (years) 65–75 (88) 76–85 (52) 485 (26) P-value
67 (59, 75) 62 (51, 73) 61 (42, 80) NS
1.38 (1.30, 1.47) 1.26 (1.16, 1.36) 1.14 (1.00, 1.29) o0.019
8.0 (7.3, 8.7) 7.6 (7.1, 8.2) 7.1 (6.4, 7.9) NS
39 (34, 45) 32 (37, 38) 28 (21, 35) o0.063
Season Spring (36) Summer (28) Fall (31) Winter (71) P-value
47 (41, 54) 52 (44, 60) 42 (36, 48) 85 (75, 96) o0.001
1.26 1.22 1.29 1.35
6.5 7.1 8.5 8.2
33 51 44 32
Origin Hospitalized (64) Outpatients (103) P-value
74 (61, 87) 57 (53, 62) 0.006
1.19 (1.11, 1.29) 1.35 (1.28, 1.44) 0.011
8.0 (7.5, 8.5) 7.6 (6.9, 8.3) NS
25 (21, 29) 45 (39, 52) o0.001
Albumin (g/dl) 43.5 (100) o3.5 (30) P-value
69 (61, 77) 49 (36, 63) 0.016
1.35 (1.27, 1.41) 1.10 (0.97, 1.23) 0.002
7.6 (7.2, 8.0) 8.4 (6.8, 10.0) NS
38 (34, 42) 21 (14, 27) o0.001
Cholesterol (mg/dl) 4150 (93) o150 (46) P-value
65 (59, 71) 68 (52, 85) NS
1.42 (1.35, 1.50) 1.04 (0.95, 1.13) o0.001
7.3 (7.0, 7.7) 8.6 (7.6, 9.7) 0.006
34 (30, 38) 33 (27, 40) NS
Ferritin (ng/ml) o300 (66) 4300 (40) P-value
63 (55, 70) 78 (61, 95) NS
1.27 (1.19, 1.35) 1.23 (1.11, 1.35) NS
7.5 (6.7, 8.3) 8.6 (7.9, 9.3) 0.046
36 (31,42) 25 (20, 30) 0.005
C-reactive protein (mg/l) o10 (34) 410 (33) P-value
81 (65, 97) 77 (59, 96) NS
1.43 (1.30, 1.55) 1.19 (1.06, 1.32) 0.010
8.2 (7.3, 9.0) 8.1 (7.6, 8.7) NS
35 (28, 42) 22 (17, 27) 0.004
Creatinine (mg/dl) o1.1 (93) 41.1 (48) P-value
53 (49, 57) 89 (76, 102) o0.001
1.27 (1.20, 1.34) 1.30 (1.18, 1.41) NS
7.4 (6.9, 7.9) 8.5 (7.9, 9.1) 0.013
39 (35, 44) 33 (27, 38) NS
GFR (ml/min 1.73 m2) o60 (77) 460 (63) P-value
83 (71, 95) 53 (47, 59) o0.001
1.28 (1.18, 1.39) 1.31 (1.23, 1.40) NS
8.3 (7.7, 8.8) 7.4 (6.7, 8.1) NS
31 (26, 36) 37 (32, 41) NS
(1.12, (1.09, (1.11, (1.26, NS
1.39) 1.34) 1.47) 1.44)
(6.0, 7.1) (6.4, 7.9) (6.6, 10.5) (7.7, 8.6) 0.013
(27, 39) (37, 66) (28, 60) (27, 36) 0.009
Abbreviations: CI, confidence intervals; GFR, estimated glomerular filtration rate; NS, not significant. One-way analysis of variance. NS: Po0.05.
European Journal of Clinical Nutrition (2013) 1325 – 1327
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Fat-soluble vitamin status in the elderly F Granado-Lorencio et al
1327 hospitalized subjects. Outpatients showed significant higher levels of vitamins E and D than hospitalized patients. Season and hospitalization affected significantly serum levels of vitamin D and A, and to a lesser extent vitamin E or the a-tocopherol/cholesterol ratio (Table 2), and a clear decreasing trend with age was observed for vitamins D, E and the a-tocopherol/cholesterol ratio. Hypoalbuminemia was associated with lower concentrations of vitamin A and D, and low serum cholesterol levels were related to a lower vitamin E and a-tocopherol/cholesterol ratio. High levels of CRP and ferritin were associated with lower levels of vitamin D and E, and an impaired renal function (high serum creatinine and low glomerular filtrate) was related to higher serum retinol levels. Consequently, in hospitalized subjects, an inadequate nutritional status and a high acute-phase response were associated with a higher prevalence of vitamins D and E deficiency (up to 97 and 15%, respectively), whereas an impaired renal diminished the prevalence of vitamin A (up to 8% using the cutoff for creatinine). DISCUSSION Aging is associated with an increasing prevalence of malnutrition, a consistent finding across all settings including communitydwelling elderly, nursing home residents and geriatric hospital patients.1 In this study, we observed a high prevalence of inadequate nutritional status and a clear decreasing trend with age for vitamins E and D. However, the prevalence of inadequacy was especially high in hospitalized patients, being even higher than the rates of malnutrition previously observed in the PREDyCES study,7 a fact probably related to the study design (that is, geographical settings, sample size, inclusion criteria and so on). Suboptimal micronutrient intake for particular vitamins (vitamins A, E and D) is common in older adults,9 although highly variable depending both on the country and the vitamin (that is, from 0% for vitamin B12 to 100% for vitamin D).5,9–11 In addition, hospitalization influences vitamin and nutritional status,6,7 and pathological conditions and their treatment can both cause malnutrition. Consistently, in hospitalized subjects, we found higher rates of both vitamin and nutritional markers inadequacy reaching values of 97% for vitamin D. The cause of malnutrition is multifactorial including diseaserelated metabolic effects, reduced dietary intake and polimedication. Unfortunately, the lack of this information in the present study constitutes a major limitation to draw more robust conclusions. In addition, nutritional biomarkers can also be influenced by many factors. As shown, an impaired renal function was related to a reduced prevalence of vitamin A deficiency in hospitalized patients, a fact possibly unrelated to diet but because of a decreased retinol clearance. Also, the higher prevalence of vitamin deficiency in hospitalized subjects was associated with inadequate levels of nutritional markers and elevated acute-phase reactants. These factors, however, do not explain the high rate of vitamin D deficiency in outpatients, so that other factors such as age, season or dietary imbalance are probably more relevant contributors in this group. In conclusion, nutritional status of fat-soluble vitamins in subjects aged 465 years is highly variable and determined by
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age, season, hospitalization, nutritional status, inflammation and renal function. Given the high prevalence of malnutrition and its impact on patient morbidity–mortality and health-care costs, an integrated nutritional care for patients while in hospital should be placed, although this measure has not been applied either in the majority of hospitals in Europe or in Spanish hospitals.7 For hospitalized patients, what indicators of vitamin status deserve to be routinely measured and which other markers should be evaluated to interpret correctly the vitamin status of the patient remains to be defined. Owing to the current trend to reduce the hospital stay, the best approach to assess, provide nutritional support and monitor the vitamin status at preadmission, in hospital and post-discharge remains to be established and deserve additional studies.
CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS The present study was performed as part of our clinical assistance to the patients and no other public or private sources of funding were used.
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European Journal of Clinical Nutrition (2013) 1325 – 1327
