Serum folate predicts muscle strength: a pilot cross-sectional study of the association between serum vitamin levels and muscle strength and gait measures in patients >65 years old with diabetes mellitus in a primary care setting

Andrew Kien Han Wee, Andrew Kien Han Wee

Abstract

Background: Old age and diabetes mellitus are risk factors for vitamin deficiencies, weakness and falls. Deficiencies of vitamin D, and possibly vitamin B12 and folate (which are associated with hyperhomocysteinaemia), contribute to sarcopenia. Determination of the physical effects of vitamin deficiencies in specific groups of people can help to guide public health policy with regard to vitamin supplementation.

Methods: A pilot cross-sectional study was conducted to determine the association of levels of vitamin D, vitamin B12, folate and homocysteine with muscle strength, gait and fall history in 56 patients >65 years old with diabetes mellitus in primary care in Singapore. Hand-grip and leg-quadriceps strength measures were obtained and divided by body mass index (BMI). The timed up-and-go and Tinetti tests were used to measure gait. A history of "at least one fall in the preceding year" was obtained.

Results: Vitamin B12 deficiency (<150 pmol/l) was present in 43 % of patients, folate deficiency (<13.5 mmol/l) in 20 %, hyperhomocysteinaemia (≥15.0 μmol/l) in 52 % and vitamin D deficiency (<49.9 nmol/l) in 25 %. Levels of vitamin D, vitamin B12 and homocysteine did not significantly predict muscle strength in regression analyses. Folate (B = 0.010, P < 0.01) and gender (B = 0.356, P < 0.001) predicted average grip strength corrected for BMI (F(2,53) = 17.74, P < 0.001, R 2 = 0.40) Folate (B = 0.011, P < 0.05) and gender (B = 0.367, P < 0.001) also predicted average leg quadriceps strength corrected for BMI (F(2,53) = 9.79, P < 0.001, R 2 = 0.27). Average leg strength and average leg strength corrected for BMI were both negatively associated with the risk of having fallen in the preceding year (odds ratio (OR) = 0.89, 95 % CI 0.80-0.98, P < 0.05 and OR = 0.12, 95 % CI 0.02-0.92, P < 0.05, respectively).

Conclusions: The prevalence of vitamin deficiency was very high in our sample of patients >65 years old with diabetes mellitus. Folate levels were significantly correlated with grip and leg strength (with correction for BMI). Leg strength was positively correlated with gait measures and negatively correlated with a history of falls. The role of folate in muscle weakness and falls warrants further study.

Keywords: Falls; Fast-gait speed; Homocysteine; Sarcopenia; Vitamin B12; Vitamin D.

Figures

Fig. 1
Fig. 1
Venn diagram of the deficiencies in vitamin B12, folate, and vitamin D (n = 56 patients)
Fig. 2
Fig. 2
Serum levels of folate and measures of strength in individual patients. For each of the 28 female and 28 male participants, serum folate was plotted against a the average leg strength (corrected for BMI) and b the average hand-grip strength (corrected for BMI)
Fig. 3
Fig. 3
Functional relationships between vitamin B12, folate and homocysteine. dUMP, deoxyuridine monophosphate; dTMP, deoxythymidine monophosphate; MS, methionine synthase; MTase, methyltransferase; MTHFR, methylenetetrahydrofolate reductase; SAHH, S-adenosylhomocysteine hydrolase; TS, thymidylate synthase

References

    1. Department of Statistics Singapore. Key Indicators on the Elderly . Accessed 24 Apr 2016.
    1. Ministry of Health Singapore. National Health Survey 2010 SINGAPORE . Accessed 24 Apr 2016.
    1. Toh E. The Straits Times. Seniors Resilient but Many Don't Exercise . Accessed 24 Apr 2016.
    1. Koh WP, Wang R, Ang LW, Heng D, Yuan JM, Yu MC. Diabetes and risk of hip fracture in the Singapore Chinese Health Study. Diabetes Care. 2010;33(8):1766–70. doi: 10.2337/dc10-0067.
    1. Foo CL, Chan KC, Goh HK, Seow E. Profiling acute presenting symptoms of geriatric patients attending an urban hospital emergency department. Ann Acad Med Singapore. 2009;38(6):515–6.
    1. Neo JJ, Kong KH. Prevalence of vitamin D deficiency in elderly patients admitted to an inpatient rehabilitation unit in tropical Singapore. Rehabil Res Pract. 2016;2016:9689760.
    1. Ramason R, Selvaganapathi N, Ismail NH, Wong WC, Rajamoney GN, Chong MS. Prevalence of vitamin d deficiency in patients with hip fracture seen in an orthogeriatric service in sunny singapore. Geriatr Orthop Surg Rehabil. 2014;5(2):82–6. doi: 10.1177/2151458514528952.
    1. Robien K, Butler LM, Wang R, Beckman KB, Walek D, Koh WP, et al. Genetic and environmental predictors of serum 25-hydroxyvitamin D concentrations among middle-aged and elderly Chinese in Singapore. Br J Nutr. 2013;109(3):493–502. doi: 10.1017/S0007114512001675.
    1. Clarke R, Refsum H, Birks J, Evans JG, Johnston C, Sherliker P, et al. Screening for vitamin B-12 and folate deficiency in older persons. Am J Clin Nutr. 2003;77(5):1241–7.
    1. Tomkin GH, Hadden DR, Weaver JA, Montgomery DA. Vitamin-B12 status of patients on long-term metformin therapy. Br Med J. 1971;2(5763):685–7. doi: 10.1136/bmj.2.5763.685.
    1. de Jager J, Kooy A, Lehert P, Wulffele MG, van der Kolk J, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181. doi: 10.1136/bmj.c2181.
    1. Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Seaquist D, Topolski R. The prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: a cross-sectional study. J Am Board Fam Med. 2009;22(5):528–34. doi: 10.3122/jabfm.2009.05.090044.
    1. Holick MF. Vitamin D, deficiency. N Engl J Med. 2007;357(3):266–81. doi: 10.1056/NEJMra070553.
    1. Kalyani RR, Stein B, Valiyil R, Manno R, Maynard JW, Crews DC. Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis. J Am Geriatr Soc. 2010;58(7):1299–310. doi: 10.1111/j.1532-5415.2010.02949.x.
    1. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009;339:b3692. doi: 10.1136/bmj.b3692.
    1. Fetahu IS, Hobaus J, Kallay E. Vitamin D and the epigenome. Front Physiol. 2014;5:164. doi: 10.3389/fphys.2014.00164.
    1. Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349:g5226. doi: 10.1136/bmj.g5226.
    1. Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149–60. doi: 10.1056/NEJMcp1113996.
    1. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. doi: 10.1186/1475-2891-14-6.
    1. Matteini AM, Walston JD, Fallin MD, Bandeen-Roche K, Kao WH, Semba RD, et al. Markers of B-vitamin deficiency and frailty in older women. J Nutr Health Aging. 2008;12(5):303–8. doi: 10.1007/BF02982659.
    1. Kojima G. Frailty as a predictor of future falls among community-dwelling older people: a systematic review and meta-analysis. J Am Med Dir Assoc. 2015;16(12):1027–33. doi: 10.1016/j.jamda.2015.06.018.
    1. Ansari R, Mahta A, Mallack E, Luo JJ. Hyperhomocysteinemia and neurologic disorders: a review. Journal of clinical neurology. 2014;10(4):281–8. doi: 10.3988/jcn.2014.10.4.281.
    1. Fratoni V, Brandi ML. B vitamins, homocysteine and bone health. Nutrients. 2015;7(4):2176–92. doi: 10.3390/nu7042176.
    1. van Wijngaarden JP, Doets EL, Szczecinska A, Souverein OW, Duffy ME, Dullemeijer C, et al. Vitamin B12, folate, homocysteine, and bone health in adults and elderly people: a systematic review with meta-analyses. J Nutr Metab. 2013;2013:486186.
    1. Clarke M, Ward M, Strain JJ, Hoey L, Dickey W, McNulty H. B-vitamins and bone in health and disease: the current evidence. Proc Nutr Soc. 2014;73(2):330–9. doi: 10.1017/S0029665114000044.
    1. Ng TP, Aung KC, Feng L, Scherer SC, Yap KB. Homocysteine, folate, vitamin B-12, and physical function in older adults: cross-sectional findings from the Singapore longitudinal ageing study. Am J Clin Nutr. 2012;96(6):1362–8. doi: 10.3945/ajcn.112.035741.
    1. Skrabal F. Syncope, falls and cobalamin deficiency in the old population. Clin Auton Res. 2004;14(2):60–6. doi: 10.1007/s10286-004-0179-x.
    1. Jansen L, van der Linden CM. Falling due to vitamin B12 deficiency. Ned Tijdschr Geneeskd. 2013;157(2):A5132.
    1. Ocampo Chaparro JM. Vitamin B12 deficit and development of geriatric syndromes. Colombia medica (Cali, Colombia) 2013;44(1):42–5.
    1. Olmedo C, Sacanella E, Masanes F, Formiga F, Lopez Soto A. Vitamin B12 deficiency: an unusual cause of falls in the elderly. Aging Clin Exp Res. 2004;16(3):255–6. doi: 10.1007/BF03327394.
    1. Nelson JM. Vitamin B12 deficiency in the elderly. A major contributor to falls. Adv Nurse Pract. 2001;9(11):39–41.
    1. Nagga K. Vitamin B12 and folate--a question of balance? Lakartidningen. 2005;102(41):2975.
    1. Aparicio-Ugarriza R, Palacios G, Alder M, Gonzalez-Gross M. A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population. Clin Chem Lab Med. 2015;53(8):1149–59. doi: 10.1515/cclm-2014-0784.
    1. de Benoist B. Conclusions of a WHO technical consultation on folate and vitamin B12 deficiencies. Food Nutr Bull. 2008;29(2 Suppl):S238–44. doi: 10.1177/15648265080292S129.
    1. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet. 1999;354(9176):407–13. doi: 10.1016/S0140-6736(98)11058-9.
    1. Tinetti ME. Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc. 1986;34(2):119–26. doi: 10.1111/j.1532-5415.1986.tb05480.x.
    1. Abbruzzese LD. The Tinetti performance-oriented mobility assessment tool. Am J Nurs. 1998;98(12):16J-L.
    1. Lin MR, Hwang HF, Hu MH, Wu HD, Wang YW, Huang FC. Psychometric comparisons of the timed up and go, one-leg stand, functional reach, and Tinetti balance measures in community-dwelling older people. J Am Geriatr Soc. 2004;52(8):1343–8. doi: 10.1111/j.1532-5415.2004.52366.x.
    1. Mathias S, Nayak US, Isaacs B. Balance in elderly patients: the "get-up and go" test. Arch Phys Med Rehabil. 1986;67(6):387–9.
    1. Lusardi MM, Pellecchia GL, Schulman M. Functional performance in community living older adults. J Geriatr Phys Ther. 2003;26(3):14–22. doi: 10.1519/00139143-200312000-00003.
    1. Peel NM, Kuys SS, Klein K. Gait speed as a measure in geriatric assessment in clinical settings: a systematic review. J Gerontol Ser A Biol Med Sci. 2013;68(1):39–46. doi: 10.1093/gerona/gls174.
    1. Martin HJ, Yule V, Syddall HE, Dennison EM, Cooper C, Aihie SA. Is hand-held dynamometry useful for the measurement of quadriceps strength in older people? A comparison with the gold standard Bodex dynamometry. Gerontology. 2006;52(3):154–9. doi: 10.1159/000091824.
    1. Sallinen J, Stenholm S, Rantanen T, Heliovaara M, Sainio P, Koskinen S. Hand-grip strength cut points to screen older persons at risk for mobility limitation. J Am Geriatr Soc. 2010;58(9):1721–6. doi: 10.1111/j.1532-5415.2010.03035.x.
    1. Mathiowetz V, Weber K, Volland G, Kashman N. Reliability and validity of grip and pinch strength evaluations. J Hand Surg. 1984;9(2):222–6. doi: 10.1016/S0363-5023(84)80146-X.
    1. Mathiowetz V, Kashman N, Volland G, Weber K, Dowe M, Rogers S. Grip and pinch strength: normative data for adults. Arch Phys Med Rehabil. 1985;66(2):69–74.
    1. Lord SR, Menz HB, Tiedemann A. A physiological profile approach to falls risk assessment and prevention. Phys Ther. 2003;83(3):237–52.
    1. Bril V, Kojic J, Ngo M, Clark K. Comparison of a neurothesiometer and vibration in measuring vibration perception thresholds and relationship to nerve conduction studies. Diabetes Care. 1997;20(9):1360–2. doi: 10.2337/diacare.20.9.1360.
    1. Dros J, Wewerinke A, Bindels PJ, van Weert HC. Accuracy of monofilament testing to diagnose peripheral neuropathy: a systematic review. Ann Fam Med. 2009;7(6):555–8. doi: 10.1370/afm.1016.
    1. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. Jama. 2005;293(2):217–28. doi: 10.1001/jama.293.2.217.
    1. Collin C, Wade DT, Davies S, Horne V. The Barthel ADL Index: a reliability study. Int Disabil Stud. 1988;10(2):61–3. doi: 10.3109/09638288809164103.
    1. Wade DT, Collin C. The Barthel ADL Index: a standard measure of physical disability? Int Disabil Stud. 1988;10(2):64–7. doi: 10.3109/09638288809164105.
    1. Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md State Med J. 1965;14:61–5.
    1. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3):179–86. doi: 10.1093/geront/9.3_Part_1.179.
    1. Shyamala T, Wong SF, Andiappan A, Au Eong KG, Bakshi AB, Boey D, et al. Health promotion board-ministry of health clinical practice guidelines: falls prevention among older adults living in the community. Singapore Med J. 2015;56(5):298–300. doi: 10.11622/smedj.2015073.
    1. SINGAPORE MoH. MOH Clinical Practice Guidelines 3/2008 OSTEOPOROSIS. . Accessed 19 June 2016.
    1. Lafortuna CL, Maffiuletti NA, Agosti F, Sartorio A. Gender variations of body composition, muscle strength and power output in morbid obesity. Int J Obes. 2005;29(7):833–41. doi: 10.1038/sj.ijo.0802955.
    1. Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008;13(3):216–26.
    1. Grieger JA, Nowson CA, Jarman HF, Malon R, Ackland LM. Multivitamin supplementation improves nutritional status and bone quality in aged care residents. Eur J Clin Nutr. 2009;63(4):558–65. doi: 10.1038/sj.ejcn.1602963.
    1. Swart KM, Ham AC, van Wijngaarden JP, Enneman AW, van Dijk SC, Sohl E, et al. A randomized controlled trial to examine the effect of 2-year vitamin B12 and folic acid supplementation on physical performance, strength, and falling: additional findings from the B-PROOF study. Calcif Tissue Int. 2016;98(1):18–27. doi: 10.1007/s00223-015-0059-5.
    1. Wu SW, Wu SF, Liang HW, Wu ZT, Huang S. Measuring factors affecting grip strength in a Taiwan Chinese population and a comparison with consolidated norms. Appl Ergon. 2009;40(4):811–5. doi: 10.1016/j.apergo.2008.08.006.
    1. Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al. Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc. 2014;15(2):95–101. doi: 10.1016/j.jamda.2013.11.025.
    1. Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di Iorio A, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol (Bethesda, Md : 1985) 2003;95(5):1851–60. doi: 10.1152/japplphysiol.00246.2003.
    1. Stampfer M, Willett W. Folate supplements for stroke prevention: targeted trial trumps the rest. Jama. 2015;313(13):1321–2. doi: 10.1001/jama.2015.1961.
    1. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med. 1999;159(12):1289–98. doi: 10.1001/archinte.159.12.1289.
    1. Nazki FH, Sameer AS, Ganaie BA. Folate: metabolism, genes, polymorphisms and the associated diseases. Gene. 2014;533(1):11–20. doi: 10.1016/j.gene.2013.09.063.
    1. Stark T, Walker B, Phillips JK, Fejer R, Beck R. Hand-held dynamometry correlation with the gold standard isokinetic dynamometry: a systematic review. PM & R. 2011;3(5):472–9. doi: 10.1016/j.pmrj.2010.10.025.
    1. Andrew K H Wee. 6-19. Vitamins B9 (Folate), B12 & D deficiencies and hyperhomocysteinaemia in elderly diabetics of a primary care polyclinic in Singapore – serum folate strongly predicts muscle strength. Poster session presented at: SCWD 2015 Paris. Abstracts of the 8th International Conference on Cachexia, Sarcopenia and Muscle Wasting, Paris, France, 4–6 December 2015. J. Cachexia Sarcopenia Muscle. 2015;6(4):398–509. doi:10.1002/jcsm.12087.
    1. American Medical Association. JAMA instructions on Systeme International (SI) conversion factors for selected laboratory components JAMA. 2000;283(1):134–5.

Source: PubMed

3
Subskrybuj