Advertisement

Circulating Micronutrient Biomarkers Are Associated With 3 Measures of Frailty: Evidence From the Irish Longitudinal Study on Ageing

Published:August 07, 2019DOI:https://doi.org/10.1016/j.jamda.2019.06.011

      Abstract

      Objectives

      To examine the associations between 3 frailty instruments and circulating micronutrients in a large representative sample of older adults.

      Design

      Cross-sectional data from a nationally representative cohort study conducted between October 2009 and July 2011.

      Participants and setting

      Adults age ≥50 years (n = 4068) living in the community in Ireland.

      Measurements

      Circulating micronutrients (lutein, zeaxanthin, folate, vitamin B-12, and vitamin D) were measured, transformed, and standardized. Frailty was assessed using the Frailty Phenotype, the Frailty Index, and the FRAIL Scale (fatigue, resistance, ambulation, illnesses, and loss of weight), instruments. Multinomial logistic regression determined associations between micronutrients and prefrailty or frailty. Models were adjusted for sociodemographic, lifestyle, health, and seasonal factors.

      Results

      Adjusting for age, sex, and educational attainment, all 3 measures of frailty were associated with lower levels of lutein [relative risk ratios (RRRs): 0.43‒0.63], zeaxanthin (RRRs: 0.49‒0.63), and vitamin D (RRRs: 0.51‒0.75), and with the accumulation of micronutrient insufficiencies (RRRs: 1.42‒1.90). Attenuated but significant associations were also observed with all measures of prefrailty for lutein, vitamin D, and number of micronutrient insufficiencies. The associations with frailty persisted following additional adjustment for social, lifestyle, and health and seasonal factors, and following multiple test correction.

      Conclusions and implications

      We have presented the most consistent evidence in the largest study to date that micronutrient concentrations are associated with prefrailty and frailty in older adults. Our data suggest that low micronutrient status has potential as an easily modifiable marker and intervention target for frailty and supports further investigation into micronutrient supplementation and fortification to prevent frailty and disability among older adults.

      Keywords

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to Journal of the American Medical Directors Association
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Clegg A.
        • Young J.
        • Iliffe S.
        • et al.
        Frailty in elderly people.
        Lancet. 2013; 381: 752-762
        • Crome P.
        • Lally F.
        Frailty: joining the giants.
        CMAJ. 2011; 183: 889-890
        • Van Craen K.
        • Braes T.
        • Wellens N.
        • et al.
        The effectiveness of inpatient geriatric evaluation and management units: a systematic review and meta-analysis.
        J Am Geriatr Soc. 2010; 58: 83-92
        • Fried L.P.
        • Tangen C.M.
        • Walston J.
        • et al.
        Frailty in older adults: evidence for a phenotype.
        J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
        • Mitnitski A.B.
        • Song X.
        • Rockwood K.
        The estimation of relative fitness and frailty in community-dwelling older adults using self-report data.
        J Gerontol A Biol Sci Med Sci. 2004; 59: M627-M632
        • Morley J.E.
        • Malmstrom T.K.
        • Miller D.K.
        A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans.
        J Nutr Health Aging. 2012; 16: 601-608
        • Collard R.M.
        • Boter H.
        • Schoevers R.A.
        • Oude Voshaar R.C.
        Prevalence of frailty in community-dwelling older persons: a systematic review.
        J Am Geriatr Soc. 2012; 60: 1487-1492
        • Lee J.S.
        • Auyeung T.W.
        • Leung J.
        • et al.
        Transitions in frailty states among community-living older adults and their associated factors.
        J Am Med Dir Assoc. 2014; 15: 281-286
        • Ames B.N.
        • Shigenaga M.K.
        • Hagen T.M.
        Oxidants, antioxidants, and the degenerative diseases of aging.
        Proc Natl Acad Sci U S A. 1993; 90: 7915-7922
        • Fairfield K.M.
        • Fletcher R.H.
        Vitamins for chronic disease prevention in adults: scientific review.
        JAMA. 2002; 287: 3116-3126
        • High K.P.
        Micronutrient supplementation and immune function in the elderly.
        Clin Infect Dis. 1999; 28: 717-722
        • Lane J.S.
        • Magno C.P.
        • Lane K.T.
        • et al.
        Nutrition impacts the prevalence of peripheral arterial disease in the United States.
        J Vasc Surg. 2008; 48: 897-904
        • Michelon E.
        • Blaum C.
        • Semba R.D.
        • et al.
        Vitamin and carotenoid status in older women: associations with the frailty syndrome.
        J Gerontol A Biol Sci Med Sci. 2006; 61: 600-607
        • Rizzoli R.
        Management of the oldest old with osteoporosis.
        Eur Geriatr Med. 2010; 1: 15-21
        • Semba R.D.
        • Bartali B.
        • Zhou J.
        • et al.
        Low serum micronutrient concentrations predict frailty among older women living in the community.
        J Gerontol A Biol Sci Med Sci. 2006; 61: 594-599
        • Kelaiditi E.
        • Guyonnet S.
        • Cesari M.
        Is nutrition important to postpone frailty?.
        Curr Opin Clin Nutr Metab Care. 2015; 18: 37-42
        • Malafarina V.
        • Uriz-Otano F.
        • Gil-Guerrero L.
        • Iniesta R.
        The anorexia of ageing: physiopathology, prevalence, associated comorbidity and mortality. A systematic review.
        Maturitas. 2013; 74: 293-302
        • Remond D.
        • Shahar D.R.
        • Gille D.
        • et al.
        Understanding the gastrointestinal tract of the elderly to develop dietary solutions that prevent malnutrition.
        Oncotarget. 2015; 6: 13858-13898
        • Leoncini E.
        • Nedovic D.
        • Panic N.
        • et al.
        Carotenoid Intake from Natural Sources and Head and Neck Cancer: A Systematic Review and Meta-analysis of Epidemiological Studies.
        Cancer Epidemiol Biomarkers Prev. 2015; 24: 1003-1011
        • Hak A.E.
        • Stampfer M.J.
        • Campos H.
        • et al.
        Plasma carotenoids and tocopherols and risk of myocardial infarction in a low-risk population of US male physicians.
        Circulation. 2003; 108: 802-807
        • Hamer M.
        • Chida Y.
        Intake of fruit, vegetables, and antioxidants and risk of type 2 diabetes: systematic review and meta-analysis.
        J Hypertens. 2007; 25: 2361-2369
        • Amadieu C.
        • Lefevre-Arbogast S.
        • Delcourt C.
        • et al.
        Nutrient biomarker patterns and long-term risk of dementia in older adults.
        Alzheimers Dement. 2017; 13: 1125-1132
        • Sugiura M.
        • Nakamura M.
        • Ogawa K.
        • et al.
        High serum carotenoids associated with lower risk for bone loss and osteoporosis in post-menopausal Japanese female subjects: prospective cohort study.
        PLoS One. 2012; 7e52643
        • Bohn T.
        Carotenoids, Chronic Disease Prevention and Dietary Recommendations.
        Int J Vitam Nutr Res. 2017; 87: 121-130
        • Ben-Dor A.
        • Steiner M.
        • Gheber L.
        • et al.
        Carotenoids activate the antioxidant response element transcription system.
        Mol Cancer Ther. 2005; 4: 177-186
        • Palozza P.
        • Simone R.
        • Catalano A.
        • et al.
        Lycopene prevention of oxysterol-induced proinflammatory cytokine cascade in human macrophages: inhibition of NF-kappaB nuclear binding and increase in PPARgamma expression.
        J Nutr Biochem. 2011; 22: 259-268
        • Gruszecki W.I.
        • Strzalka K.
        Carotenoids as modulators of lipid membrane physical properties.
        Biochim Biophys Acta. 2005; 1740: 108-115
        • Kennedy D.O.
        B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review.
        Nutrients. 2016; 8: 68
        • Bailey L.B.
        Folate in health and disease.
        2nd edition. CRC press, USA2017
        • Stover P.J.
        Physiology of folate and vitamin B12 in health and disease.
        Nutr Rev. 2004; 62 (discussion S13): S3-S12
        • Strickland K.C.
        • Krupenko N.I.
        • Krupenko S.A.
        Molecular mechanisms underlying the potentially adverse effects of folate.
        Clin Chem Lab Med. 2013; 51: 607-616
        • Institue of Medicine (United States)
        Dietary Reference Intakes for Calcium and Vitamin D.
        National Academies Press, Washington, DC2011
        • Pludowski P.
        • Holick M.F.
        • Pilz S.
        • et al.
        Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence.
        Autoimmun Rev. 2013; 12: 976-989
        • Skaaby T.
        The relationship of vitamin D status to risk of cardiovascular disease and mortality.
        Dan Med J. 2015; 62 (pii: B5008. Review)
        • Haussler M.R.
        • Whitfield G.K.
        • Kaneko I.
        • et al.
        Molecular mechanisms of vitamin D action.
        Calcif Tissue Int. 2013; 92: 77-98
        • Krishnan A.V.
        • Feldman D.
        Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D.
        Annu Rev Pharmacol Toxicol. 2011; 51: 311-336
        • Bartali B.
        • Frongillo E.A.
        • Bandinelli S.
        • et al.
        Low nutrient intake is an essential component of frailty in older persons.
        J Gerontol A Biol Sci Med Sci. 2006; 61: 589-593
        • Kobayashi S.
        • Asakura K.
        • Suga H.
        • et al.
        Inverse association between dietary habits with high total antioxidant capacity and prevalence of frailty among elderly Japanese women: a multicenter cross-sectional study.
        J Nutr Health Aging. 2014; 18: 827-839
        • Matteini A.M.
        • Walston J.D.
        • Fallin M.D.
        • et al.
        Markers of B-vitamin deficiency and frailty in older women.
        J Nutr Health Aging. 2008; 12: 303-308
        • Smit E.
        • Winters-Stone K.M.
        • Loprinzi P.D.
        • et al.
        Lower nutritional status and higher food insufficiency in frail older US adults.
        Br J Nutr. 2013; 110: 172-178
        • Buta B.
        • Choudhury P.P.
        • Xue Q.L.
        • et al.
        The Association of Vitamin D Deficiency and Incident Frailty in Older Women: The Role of Cardiometabolic Diseases.
        J Am Geriatr Soc. 2017; 65: 619-624
        • Ensrud K.E.
        • Blackwell T.L.
        • Cauley J.A.
        • et al.
        Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study.
        J Am Geriatr Soc. 2011; 59: 101-106
        • Ensrud K.E.
        • Ewing S.K.
        • Fredman L.
        • et al.
        Circulating 25-hydroxyvitamin D levels and frailty status in older women.
        J Clin Endocrinol Metab. 2010; 95: 5266-5273
        • Puts M.T.
        • Visser M.
        • Twisk J.W.
        • et al.
        Endocrine and inflammatory markers as predictors of frailty.
        Clin Endocrinol (Oxf). 2005; 63: 403-411
        • Vogt S.
        • Decke S.
        • de Las Heras Gala T.
        • et al.
        Prospective association of vitamin D with frailty status and all-cause mortality in older adults: Results from the KORA-Age Study.
        Prev Med. 2015; 73: 40-46
        • Wong Y.Y.
        • McCaul K.A.
        • Yeap B.B.
        • et al.
        Low vitamin D status is an independent predictor of increased frailty and all-cause mortality in older men: the Health in Men Study.
        J Clin Endocrinol Metab. 2013; 98: 3821-3828
        • Kearney P.M.
        • Cronin H.
        • O'Regan C.
        • et al.
        Cohort profile: the Irish Longitudinal Study on Ageing.
        Int J Epidemiol. 2011; 40: 877-884
        • Whelan B.J.
        • Savva G.M.
        Design and methodology of the Irish Longitudinal Study on Ageing.
        J Am Geriatr Soc. 2013; 61: S265-S268
        • Roe L.
        • Normand C.
        • Wren M.A.
        • et al.
        The impact of frailty on healthcare utilisation in Ireland: evidence from the Irish longitudinal study on ageing.
        BMC Geriatr. 2017; 17: 203
        • Moran R.
        • Nolan J.M.
        • Stack J.
        • et al.
        Non-Dietary Correlates and Determinants of Plasma Lutein and Zeaxanthin Concentrations in the Irish Population.
        J Nutr Health Aging. 2017; 21: 254-261
        • Nolan J.M.
        • Loskutova E.
        • Howard A.N.
        • et al.
        Macular pigment, visual function, and macular disease among subjects with Alzheimer's disease: an exploratory study.
        J Alzheimers Dis. 2014; 42: 1191-1202
        • Molloy A.M.
        • Scott J.M.
        Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method.
        Methods Enzymol. 1997; 281: 43-53
        • Kelleher B.P.
        • Broin S.D.
        Microbiological assay for vitamin B12 performed in 96-well microtitre plates.
        J Clin Pathol. 1991; 44: 592-595
        • Laird E.
        • O'Halloran A.M.
        • Carey D.
        • et al.
        The Prevalence of Vitamin D Deficiency and the Determinants of 25(OH)D Concentration in Older Irish Adults: Data From The Irish Longitudinal Study on Ageing (TILDA).
        J Gerontol A Biol Sci Med Sci. 2018; 73: 519-525
        • Benjamini Y.
        • Hochberg Y.
        Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing.
        1995: 289-300
        • Hammond Jr., B.R.
        • Renzi L.M.
        Carotenoids.
        Adv Nutr. 2013; 4: 474-476
        • Feeney J.
        • O'Leary N.
        • Moran R.
        • et al.
        Plasma Lutein and Zeaxanthin Are Associated With Better Cognitive Function Across Multiple Domains in a Large Population-Based Sample of Older Adults: Findings from The Irish Longitudinal Study on Aging.
        J Gerontol A Biol Sci Med Sci. 2017; 72: 1431-1436
        • Yeum K.J.
        • Beretta G.
        • Krinsky N.I.
        • et al.
        Synergistic interactions of antioxidant nutrients in a biological model system.
        Nutrition. 2009; 25: 839-846
        • Laird E.J.
        • O'Halloran A.M.
        • Carey D.
        • et al.
        Voluntary fortification is ineffective to maintain the vitamin B12 and folate status of older Irish adults: evidence from the Irish Longitudinal Study on Ageing (TILDA).
        Br J Nutr. 2018; 120: 111-120
        • Koike H.
        • Takahashi M.
        • Ohyama K.
        • et al.
        Clinicopathologic features of folate-deficiency neuropathy.
        Neurology. 2015; 84: 1026-1033
        • Peng Y.
        • Dong B.
        • Wang Z.
        Serum folate concentrations and all-cause, cardiovascular disease and cancer mortality: A cohort study based on 1999-2010 National Health and Nutrition Examination Survey (NHANES).
        Int J Cardiol. 2016; 219: 136-142
        • Vogel T.
        • Dali-Youcef N.
        • Kaltenbach G.
        • Andres E.
        Homocysteine, vitamin B12, folate and cognitive functions: a systematic and critical review of the literature.
        Int J Clin Pract. 2009; 63: 1061-1067
        • Stabler S.P.
        Clinical practice. Vitamin B12 deficiency.
        N Engl J Med. 2013; 368: 149-160
        • Wilhelm-Leen E.R.
        • Hall Y.N.
        • Deboer I.H.
        • Chertow G.M.
        Vitamin D deficiency and frailty in older Americans.
        J Intern Med. 2010; 268: 171-180
        • Zhou J.
        • Huang P.
        • Liu P.
        • et al.
        Association of vitamin D deficiency and frailty: A systematic review and meta-analysis.
        Maturitas. 2016; 94: 70-76
        • SACN (Scientific Advisory Committee on Nutrition)
        Report on Vitamin D and Health.
        Public Health England; Crown, London2016
        • Visser M.
        • Deeg D.J.
        • Lips P.
        • Longitudinal Aging Study A
        Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam.
        J Clin Endocrinol Metab. 2003; 88: 5766-5772
        • Bischoff H.A.
        • Borchers M.
        • Gudat F.
        • et al.
        In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue.
        Histochem J. 2001; 33: 19-24
        • Wilson D.
        • Jackson T.
        • Sapey E.
        • Lord J.M.
        Frailty and sarcopenia: The potential role of an aged immune system.
        Ageing Res Rev. 2017; 36: 1-10
        • Tan B.L.
        • Norhaizan M.E.
        • Liew W.P.
        • Sulaiman Rahman H.
        Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases.
        Front Pharmacol. 2018; 9: 1162
        • Lupton J.R.
        • Atkinson S.A.
        • Chang N.
        • et al.
        Exploring the benefits and challenges of establishing a DRI-like process for bioactives.
        Eur J Nutr. 2014; 53: 1-9
        • Ranard K.M.
        • Jeon S.
        • Mohn E.S.
        • et al.
        Dietary guidance for lutein: consideration for intake recommendations is scientifically supported.
        Eur J Nutr. 2017; 56: 37-42
        • Thomas J.B.
        • Duewer D.L.
        • Mugenya I.O.
        • et al.
        Preparation and value assignment of standard reference material 968e fat-soluble vitamins, carotenoids, and cholesterol in human serum.
        Anal Bioanal Chem. 2012; 402: 749-762

      Supplementary References

        • Fried L.P.
        • Ferrucci L.
        • Darer J.
        • et al.
        Untangling the concepts of disability, frailty, and comorbidity: Implications for improved targeting and care.
        J Gerontol A Biol Sci Med Sci. 2004; 59: 255-263
        • Fried L.P.
        • Tangen C.M.
        • Walston J.
        • et al.
        Frailty in older adults: evidence for a phenotype.
        J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
        • Moran R.
        • Nolan J.M.
        • Stack J.
        • et al.
        Non-Dietary Correlates and Determinants of Plasma Lutein and Zeaxanthin Concentrations in the Irish Population.
        J Nutr Health Aging. 2017; 21: 254-261
        • Nolan J.M.
        • Loskutova E.
        • Howard A.N.
        • et al.
        Macular pigment, visual function, and macular disease among subjects with Alzheimer's disease: an exploratory study.
        J Alzheimers Dis. 2014; 42: 1191-1202
        • Kelleher B.P.
        • Broin S.D.
        Microbiological assay for vitamin B12 performed in 96-well microtitre plates.
        J Clin Pathol. 1991; 44: 592-595
        • Molloy A.M.
        • Scott J.M.
        Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method.
        Methods Enzymol. 1997; 281: 43-53
        • Laird E.
        • O'Halloran A.M.
        • Carey D.
        • et al.
        The Prevalence of Vitamin D Deficiency and the Determinants of 25(OH)D Concentration in Older Irish Adults: Data From The Irish Longitudinal Study on Ageing (TILDA)..
        J Gerontol A Biol Sci Med Sci. 2018; 73: 519-525