Relationship between serum B12 concentrations and mortality: experience in NHANES

Abstract

Background There is conflicting evidence in the literature on the association between (elevated) serum B12 concentrations and subsequent disease or mortality. We evaluated in the NHANES general population the association of serum B12 concentrations as well as vitamin B12 supplement intake with all-cause, cardiovascular, and cancer-related mortality, while taking into account demographic and lifestyle factors and significant other diseases which are known to be associated with poorer outcome. Methods The main outcomes of our study were all-cause mortality, cardiovascular mortality, and cancer-related mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index public access files through December 31, 2015. The association of serum B12 concentrations and vitamin B12 supplement intake with mortality was assessed with Cox proportional hazard (PH) models, with adjustment for a number of relevant demographic and lifestyle factors and comorbidity. Results The final study population of 24,262 participants had a mean age of 48 (SD 19) years; 50.1% were males. The median follow-up duration was 109 months (range 1–201 months). On the census day of December 31, 2015, 3023 participants were determined as deceased (12.5%). The fully adjusted Cox PH model indicated that low serum B12 concentrations < 140 pmol/l were associated with a small increase in all-cause (hazard ratio, HR 1.39, 95% CI 1.08–1.78, p = 0.011) and cardiovascular (HR 1.64, 95% CI 1.08–2.47, p = 0.020) mortality. Similarly, high serum B12 concentrations > 700 pmol/l were associated with an increase in cardiovascular mortality only (HR 1.45, 95% CI 1.01–2.06, p = 0.042). Participants with a diagnosis of hypertension, dyslipidemia, CVD, and cancer more frequently used vitamin B12-containing supplements than those without these diagnoses. We could not demonstrate an association between vitamin B12 supplement intake and mortality, when adjusted for comorbidity. Conclusions In the general population of NHANES, low serum B12 concentrations were associated with a moderate increase in all-cause mortality. There was a small but significant increase in cardiovascular mortality in the groups with low or high serum B12. High intake of vitamin B12 in the form of supplements was not associated with any adverse effect on mortality and therefore can be regarded as safe.

Is There a Carcinogenic Risk Attached to Vitamin B12 Deficient Diets and What Should We Do About It? Reviewing the Facts

“…[87] Others have suggested that rather a daily oral dosage of 10 µg of B 12 is sufficient. [4] Despite the difference in numbers, supplementation is generally advised for individuals who consume a diet low in B 12 and may have a positive impact on public health [88] and possibly reduce the risk of developing cancer (but see above). [61] Although not commonly used, B 12 supplements can be administered nasally and sublingually as well.…”

Fruit and Vegetable Intake and Telomere Length in a Random Sample of 5448 U.S. Adults

“…Concurrent validity of the NHANES 24 h diet assessment has been established through numerous studies. For example, results derived using the NHANES 24 h recall are predictive of non-alcoholic fatty liver disease [ 30 ], total mortality [ 31 ], cardiovascular mortality [ 32 ], cancer mortality [ 33 ], and coronary heart disease [ 34 ], to name a few.…”

The role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle–gut–brain axis and implications for SARS-CoV-2 infection

“…In data from 24 262 participants with a mean age of 48.0 (SD, ± 19.0) years, Wolffenbuttel et al 130 found that low serum B 12 concentrations (< 140 pmol/L) were associated with a moderate increase in all causes of death (eg, chronic lower respiratory diseases, Alzheimer’s disease, influenza and pneumonia, cerebrovascular diseases, diabetes mellitus) and high serum concentrations of MMA and Hcy; the increase in cardiovascular causes of death was associated with both low (< 140 pmol/L) and high (> 700 pmol/L) serum B 12 levels.…”