{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:41:33Z","timestamp":1783942893534,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T00:00:00Z","timestamp":1384214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>This study was designed to assess whether symptoms, functional measures, and reported disabilities were associated with vitamin B12 (B12) deficiency when defined in three ways. Participants, aged 60 or more years of age, in 1999\u20132002 National Health and Nutrition Examination Surveys (NHANES) were categorized in relation to three previously used definitions of B12 deficiency: (1) serum B12 &lt; 148 pmol\/L; (2) serum B12 &lt; 200 pmol\/L and serum homocysteine &gt; 20 \u03bcmol\/L; and (3) serum B12 &lt; 258 pmol\/L or serum methylmalonic acid &gt; 0.21 \u03bcmol\/L. Functional measures of peripheral neuropathy, balance, cognitive function, gait speed, along with self-reported disability (including activities of daily living) were examined with standardized instruments by trained NHANES interviewers and technicians. Individuals identified as B12 deficient by definition 2 were more likely to manifest peripheral neuropathy OR (odds) (95% confidence intervals),  p value: 9.70 (2.24, 42.07), 0.004 and report greater total disability, 19.61  (6.22, 61.86) 0.0001 after adjustments for age, sex, race, serum creatinine, and ferritin concentrations, smoking, diabetes, and peripheral artery disease. Smaller, but significantly increased, odds of peripheral neuropathy and total disability were also observed when definition 3 was applied. Functional measures and reported disabilities were associated with B12 deficiency definitions that include B12 biomarkers (homocysteine or methylmalonic acid). Further study of these definitions is needed to alert clinicians of possible subclinical B12 deficiency because functional decline amongst older adults may be correctable if the individual is B12 replete.<\/jats:p>","DOI":"10.3390\/nu5114462","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T10:43:07Z","timestamp":1384252987000},"page":"4462-4475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Vitamin B12 Deficiency in Relation to Functional Disabilities"],"prefix":"10.3390","volume":"5","author":[{"given":"Breanna","family":"Oberlin","sequence":"first","affiliation":[{"name":"Diabetes Research Group, Seattle Institute of Biomedical and Clinical Research,  1660 S. Columbian Way, DPP-151, Seattle, WA 98108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Tangney","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Rush University Medical Center, 1700 West Van Buren St.,  Suite 425, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Gustashaw","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Rush University Medical Center, 1700 West Van Buren St.,  Suite 425, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Rush University Medical Center, 1700 West Van Buren St.,  Suite 425, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,11,12]]},"reference":[{"key":"ref_1","unstructured":"Institute of Medicine (1998). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, National Academy Press."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1093\/ageing\/afg109","article-title":"Vitamin B12 and folate deficiency in later life","volume":"33","author":"Clarke","year":"2004","journal-title":"Age Ageing"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/ajcn\/46.3.387","article-title":"The 1986 Herman Award Lecture. Nutrition science as a continually unfolding story, the folate and vitamin B12 paradigm","volume":"46","author":"Herbert","year":"1987","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1365-2796.2004.01393.x","article-title":"A population-based intervention study on elevated serum levels of methylmalonic acid and total homocysteine in elderly people, results after 36 months of follow-up","volume":"256","author":"Bjorkegren","year":"2004","journal-title":"J. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/gerona\/glr202","article-title":"Vitamin B12 and homocysteine levels and 6-year change in peripheral nerve function and neurological signs","volume":"67","author":"Lesihear","year":"2012","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1093\/ajcn\/81.5.1155","article-title":"Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy, a placebo-controlled randomized study","volume":"81","author":"Lewerin","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1017\/S1368980009990279","article-title":"Association between vitamin B12-containing supplement consumption and prevalence of biochemically defined B12 deficiency in adults in NHANES III (Third National Health and Nutrition Examination Survey)","volume":"13","author":"Evatt","year":"2009","journal-title":"Public Health Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/ajcn\/85.1.193","article-title":"Folate and vitamin B-12 status in relation to anemia, macrocytosis and cognitive impairment in older Americans in the age of folic acid fortification","volume":"85","author":"Morris","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s12603-010-0077-y","article-title":"Vitamin B12 deficiency in African Americans and white octogenarians and centenarians in Georgia","volume":"14","author":"Johnson","year":"2010","journal-title":"J. Nutr. Health Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1111\/j.1532-5415.1992.tb03641.x","article-title":"High prevalence of cobalamin deficiency in elderly outpatients","volume":"40","author":"Pennypacker","year":"1992","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1182\/blood.V76.5.871.871","article-title":"Clinical spectrum and diagnosis of cobalamin deficiency","volume":"76","author":"Stabler","year":"1990","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1093\/ageing\/afl033","article-title":"Clinical relevance of low serum vitamin B12 concentrations in older people, the Banbury B12 study","volume":"36","author":"Hin","year":"2006","journal-title":"Age Ageing"},{"key":"ref_13","unstructured":"NHANES Centers for Disease Control and Prevention, National Health and Nutrition Examination Survey 2001\u20132002, Available online:http:\/\/wwwn.cdc.gov\/nchs\/nhanes\/search\/datapage.aspx?Component=Examination&CycleBeginYear=2001."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.2337\/diacare.27.7.1591","article-title":"Prevalence of lower-extremity disease in the US adult population \u2265 40 years of age with and without diabetes, 1999\u20132000 National Health and Nutrition Examination survey","volume":"27","author":"Gregg","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_15","unstructured":"The Psychological, Corporation (1997). WAIS-III, Wechsler Adult Intelligence Scale, Harcourt Brace and Company. [3rd ed.]."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1159\/000096792","article-title":"Cognitive function, habitual gait speed, and late-life disability in the National Health and Nutrition Examination Survey (NHANES) 1999\u20132002","volume":"53","author":"Kuo","year":"2007","journal-title":"Gerontology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/j.1532-5415.2004.52268.x","article-title":"Isokinetic leg muscle strength in older Americans and its relationship to a standardized walk test. Data from the National Health and Nutrition Examination Survey 1999\u20132000","volume":"52","author":"Ostchega","year":"2004","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/ageing\/29.5.441","article-title":"Walking speed as a good predictor for the onset of functional dependence in a Japanese rural community population","volume":"29","author":"Shinkai","year":"2002","journal-title":"Age Ageing"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"439","DOI":"10.2307\/3349677","article-title":"An epidemiology of disability among adults in the United States","volume":"54","author":"Nagi","year":"1976","journal-title":"Milbank Mem. Fund Q. Health Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/00005792-199107000-00001","article-title":"Neurologic aspects of cobalamin deficiency","volume":"70","author":"Healton","year":"1991","journal-title":"Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/j.1532-5415.1992.tb01939.x","article-title":"Time dependency of cognitive recovery with cobalamin replacement, report of a pilot study","volume":"40","author":"Martin","year":"1992","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/ajcn\/60.1.2","article-title":"Prevalence of cobalamin deficiency in the Framingham elderly population","volume":"60","author":"Lindenbaum","year":"1994","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1532-5415.1995.tb06093.x","article-title":"Social and leisure activities and risk of dementia, a prospective longitudinal study","volume":"43","author":"Fabrigoule","year":"1995","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/BF02982659","article-title":"Markers of B-vitamin deficiency and frailty in older women","volume":"12","author":"Matteini","year":"2008","journal-title":"J. Nutr. Health Aging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1212\/WNL.57.12.2236","article-title":"Influence of leisure activity on the incidence of Alzheimer\u2019s disease","volume":"57","author":"Scarmeas","year":"2001","journal-title":"Neurology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1212\/01.wnl.0000341272.48617.b0","article-title":"Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline","volume":"72","author":"Tangney","year":"2009","journal-title":"Neurology"},{"key":"ref_27","first-page":"48","article-title":"Effectiveness of vitamin B12 on diabetic neuropathy, Systematic review of clinical controlled trials","volume":"14","author":"Sun","year":"2008","journal-title":"Acta Neurol. Taiwan"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/5\/11\/4462\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:50:32Z","timestamp":1760219432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/5\/11\/4462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,12]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,11]]}},"alternative-id":["nu5114462"],"URL":"https:\/\/doi.org\/10.3390\/nu5114462","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,12]]}}}