Benefit of vitamin B-12 supplementation in asymptomatic elderly: a matter of endpoints

Abstract

The myth and panacea of vitamin B-12 have attracted many scientists in the past century. Six Nobel Prizes have been awarded to the scientists who worked on vitamin B-12: George Hoyt Whipple, George Richards Minot, and William Parry Murphy were awarded the prize in 1934 for the discovery of vitamin B-12; Robert B Woodward received it in 1965 for synthesis of vitamin B-12; and Lord Todd and Dorothy Crowfoot Hodgkin were awarded in 1957 and 1964, respectively, for discovering the structure of vitamin B-12. The journey of vitamin B-12 was started as a panacea for anemia, followed by a definite association with subacute combined degeneration and remarkable improvement with vitamin B-12, and lately a controversial role of vitamin B-12 in prevention of dementia and cardiovascular complications. The prevalence of vitamin B-12 deficiency in industrialized countries ranges between 2% and 20% and may occur in 30% in elderly malnourished sick individuals. In the Framingham study, the prevalence of vitamin B-12 deficiency in the elderly was 12% (1). Vitamin B-12 is an essential cofactor in 2 enzymatic pathways in mammalian cells. It acts as a cofactor with methionine synthase to convert homocysteine to methionine and with L-methylmalonyl-CoA mutase to convert methylmalonyl-CoA to succinyl-CoA. Humans are unable to synthesize cobalamin; hence, an exogenous supply is essential. The daily requirement of vitamin B-12 in adults is 2.4 lg/d, and only 1-5% of crystalline cobalamin is absorbed. In the elderly, the absorption is reduced; hence, the daily requirement is higher than in younger individuals. Vitamin B-12 deficiency can result from pernicious anemia; vegetarianism; poor intake in isolated, elderly, or psychiatric patients; food cobalamin absorption; gastric or ileal resection; malabsorption; alcohol intake; Sjogren syndrome; deficiency in transcobalamin II, intracellular enzymes, or haptocorin; and frequent use of certain drugs (e.g., H2-receptor antagonists, proton-pump inhibitors, biguanids).The clinical manifestations of vitamin B-12 deficiency are diverse and include hematologic, skin, behavioral, and neurologic manifestations. The frequency of neuropsychiatric and cognitive abnormalities in vitamin B-12 deficiency depends on the extent of evaluation. In one study, 42% of patients with vitamin B-12 deficiency neurological syndrome (VBDNS) had abnormalities on neuropsychiatric inventory; these included anxiety, apathy, aggression, irritability, hallucinations, delusions, and disinhibition, in descending order (2). In another study of VBDNS (3), myelopathy was present in 93% of patients, cognitive impairment in 48%, and neuropathy in 44%. Combined syndromes were common, and the isolated syndrome occurred in only 2% of patients. Healton et al. (4) reported myelopathy and encephalopathy in 88% and 15% of patients, respectively. Dementia in VBDNS is mild to moderate, although initial studies reported megaloblastic madness (5). Detailed cognitive testing in VBDNS revealed frontal-subcortical neurobehavioral and cognitive abn...

Evaluation of optic nerve functions in subacute combined degeneration using visual evoked potential and diffusion tensor imaging—a pilot study

“…13 Optic nerve demyelinating changes in MS are different from SACD, because SACD patients are usually asymptomatic, conventional MRI sequences do not reveal any signal abnormality, although half the patients have prolongation of P100 latency in VEP which normalizes following cobalamine treatment. 1,5,7 These changes are consistent with myelin dysfunction of optic nerve which is further supported by reduced FAR and increased RDR and MDR on DTI with prolonged P100 latency on PSVEP in the present study. Moreover, optic nerve diameter in SACD patients was comparable to controls.…”

Association of Vitamin B12, Folate, and Sulfur Amino Acids With Brain Magnetic Resonance Imaging Measures in Older Adults

“…1 High levels of tHcy and low levels of vitamin B 12 and folate are common in the elderly and are associated with a variety of disorders, including cardiovascular and cerebrovascular conditions. [2][3][4][5] In addition, they may influence brain structure through several mechanisms. 4 In older adults, substantial cerebral atrophy is associated with a diagnosis of dementia, which is maintained in very advanced age.…”

Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review

“…There have been a few randomized controlled trials on the benefits of supplementation on neurologic function in people with marginal B12 status. A recent study on elderly subjects with marginal B12 status residing in the United Kingdom failed to see benefits of 12 mo of B12 supplements on a battery of electrophysiologic measures of peripheral and central nerve function (44), although this trial has been criticized for use of insensitive outcome measures (45). In contrast, B12 treatment of Chilean elderly subjects with serum B12 <120 pmol/L at screening improved conductivity in myelinated peripheral nerves (37).…”