Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study

Abstract

BackgroundFolate and vitamin B12 are keys to the correct functioning of one-carbon (1-C) metabolism. The current evidence on associations between 1-C metabolism biomarkers and mortality is inconclusive and generally based on younger or institutionalized populations. This study aimed to determine the associations between biomarkers of 1-C metabolism and all-cause and cardiovascular (CVD) mortality in the very old.MethodsThe Newcastle 85+ Study is a prospective longitudinal study of participants aged 85 at recruitment living in Northeast England. Baseline red blood cell folate (RBC folate), plasma vitamin B12, and total homocysteine (tHcy) concentrations were available for 752–766 participants. Associations between biomarkers of 1-C metabolism and all-cause and CVD mortality for up to 9 years were assessed by Cox proportional hazard models and confirmed by restricted cubic splines.ResultsParticipants with higher tHcy concentrations had higher risk of death from any cause (hazard ratio [HR] [×10 μmol/L]: 1.24, 95% confidence interval [CI]: 1.10–1.41) and cardiovascular diseases (HR [×10 μmol/L]: 1.23, 95% CI: 1.04–1.45) than those with lower concentrations; and women with higher plasma vitamin B12 concentrations had increased risk of all-cause and cardiovascular mortality (HR [×100 pmol/L]: 1.10, 95% CI: 1.04–1.16) after adjustment for key sociodemographic, lifestyle, and health confounders.ConclusionHigher concentrations of tHcy in all participants and plasma vitamin B12 in women were associated with increased risk of all-cause and CVD mortality in the very old. This confirms findings for tHcy in younger populations but the adverse relationships between elevated plasma vitamin B12 concentrations and mortality in this setting are novel and require further investigation.

Association of Plasma Concentration of Vitamin B12With All-Cause Mortality in the General Population in the Netherlands

“…Baseline characteristics, such as older age, high blood pressure, reduced eGFR, and elevated UAE rate, as well as increased concentrations of liver enzymes, were positively associated with higher plasma concentrations of vitamin B 12 , in agreement with findings from other studies. 3,8,11 While the cross-sectional associations as found in this study do not provide an insight for a particular cause of death, we observed that high circulating vitamin B 12 plasma concentrations were associated with significantly higher risk of all-cause mortality. The association remained significant after adjustment for established risk factors, including age, sex, BMI, type 2 diabetes, tobacco use, and alcohol consumption, as well as biomarkers associated with renal and liver function.…”

“…1 While the deleterious effects of vitamin B 12 deficiency, such as anemia, neuropsychiatric symptoms, and other clinical manifestations, are well established, 2 the potential association of high plasma concentrations of vitamin B 12 with adverse health outcomes has not been fully explored. 3 Indeed, a potential association of high vitamin B 12 plasma concentrations with excess mortality has been assessed in elderly [3][4][5][6][7][8][9] and hospitalized 10,11 populations, but it has not been explored in the general population, to our knowledge.…”

Asociación entre niveles de vitamina B-12 y mortalidad en pacientes hospitalizados adultos mayores

“…Una de las fortalezas de este estudio es análisis prospectivo en el contexto de pacientes admitidos en un servicio de medicina interna, ≥ 65 años, y considerando variables conocidas asociadas a mortalidad. La literatura disponible informa resultados similares en pacientes adultos mayores [4][5][6] y otros estudios publicaron resultados similares en la población hospitalaria 11 . Finalmente, nuestras limitaciones incluyen un alto número de datos incompletos y un reclutamiento bajo durante el período de estudio, que restringió el tamaño de la muestra a 93 pacientes, acotado a un solo centro de un hospital de alta complejidad en Chile.…”

“…Si bien el déficit de vitamina B-12 es más prevalente en individuos con baja ingesta oral (dieta estricta, veganos), edad avanzada, trastornos autoinmunes como la anemia perniciosa y alteraciones en la absorción intestinal (gastrectomía, enfermedad inflamatoria intestinal, entre otras), en los últimos años se ha reportado que tanto los niveles insuficientes como el exceso, se asocian a distintos desenlaces clínicos, por un lado, los niveles insuficientes han sido asociados con un mayor riesgo de compromiso neurológico, demencia y riesgo cardiovascular, en especial los inferiores a 200 pg/ml, mientras que exceso de vitamina B-12, en estudios recientes demostraron efectos deletéreos, en especial con niveles mayores de 1.000 pg/ml. Dentro de los desenlaces reportados se encuentra aumento del riesgo cardiovascular, asociado a mayor riesgo de muerte, efecto encontrado con mayor asociación en población adultos mayores, portadores de neoplasia [4][5][6][7] , además de comorbilidades con enfermedades hepáticas y hematológicas 7-9 y enfermedad renal crónica (ERC) en hemodiálisis 10 . Esta asociación ha demostrado ser variable independiente de mayor mortalidad y estadía hospitalaria, en especial en población hospitalizada en riesgo nutricional 11 .…”

Effect of Moxibustion on Hyperhomocysteinemia and Oxidative Stress Induced by High‐Methionine Diet

“…In addition to many traditional risk factors (such as hypertension, diabetes, hyperlipidemia, and smoking), more and more studies have focused on the relationship between homocysteine (Hcy) and atherosclerosis (AS) [1,2]. Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis [3,4].…”