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Obesity · Journal article
Current Therapeutic Research, Clinical and Experimental · June 27, 2026
Early or partial results. Treat as a signal, not a conclusion.
This prospective cohort study of 8,301 adults with obesity from NHANES (1999–2006 and 2011–2014) found an approximately U-shaped association between serum vitamin B12 levels and all-cause mortality, with an inflection point at 354 pmol/L. The authors identify a putative safe range of 300–500 pmol/L but explicitly state that the observational design precludes causal inference and that further studies are needed.
Prospective cohort study (secondary analysis of NHANES cross-sectional surveys with mortality linkage). Adults with obesity (BMI ≥30 kg/m²) from NHANES 1999–2006 and 2011–2014 with complete serum B12 levels and all-cause mortality linkage data. U.S. civilian population, all age groups.. Intervention: Serum vitamin B12 levels (observational; no intervention administered). Compared with: Comparison across quintiles and threshold analysis; no active comparator group. n = 8,301. United States (NHANES national survey).
Among 8,301 participants with obesity, 1,347 all-cause deaths occurred over median 9.08 years follow-up. Lowest groups Q1, Q2 and highest group Q5 showed significantly increased all-cause mortality risk, although P for trend was nonsignificant. Threshold effect analysis identified an inflection point of 354 pmol/L for serum vitamin B12 levels.
Lowest groups Q1, Q2 and highest group Q5 showed significantly increased all-cause mortality risk, although P for trend was nonsignificant. Below 354 pmol/L, lower B12 levels were associated with lower all-cause mortality; above threshold, higher B12 was associated with high all-cause mortality.
The finding of a U-shaped mortality risk suggests that both very low and very high vitamin B12 levels may be harmful in obese populations, challenging the assumption that 'more is better' for supplementation. However, because this is observational and causality cannot be proven, clinicians should view this as hypothesis-generating; dynamic B12 monitoring may help identify at-risk individuals, but supplementation decisions require further prospective evidence.
Observational cohort study with a U-shaped association and identified threshold effect, but the authors explicitly state causality cannot be inferred and acknowledge the need for further studies to establish causality.
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The finding of a U-shaped mortality risk suggests that both very low and very high vitamin B12 levels may be harmful in obese populations, challenging the assumption that 'more is better' for supplementation. However, because this is observational and causality cannot be proven, clinicians should view this as hypothesis-generating; dynamic B12 monitoring may help identify at-risk individuals, but supplementation decisions require further prospective evidence.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background. Despite the health benefits of vitamin B12, the potential association between vitamin B12 and all-cause mortality in populations with obesity remains understudied. Objective: To dissect this intrinsic association in adults with obesity and identify potential threshold effects. Methods: Data from 1999 to 2006 and 2011 to 2014 were retrieved from the National Health and Nutrition Examination Survey database. Three models were developed by adjusting for demographic characteristics, clinical factors, and comorbidities, and the relationship between vitamin B12 and all-cause mortality was further analyzed using Cox proportional hazards modelling, restricted cubic spline, survival curve analysis, and threshold effect analysis.Results. Among 8301 participants with 1347 all-cause mortality over median follow-up of 9.08 years, the lowest groups Q1, Q2 and the highest group Q5 showed significantly increased all-cause mortality risk, although the P for trend was nonsignificant. The unweighted threshold effect analysis showed an inflection point of 354 pmol/L for serum vitamin B12 levels. Below this point, lower B12 levels were associated with lower all-cause mortality, whereas above the threshold, higher vitamin B12 levels were associated with high all-cause mortality.Conclusions. All-cause mortality in the population with obesity showed an approximately U-shaped association with serum vitamin B12 levels. Maintaining serum B12 levels within 300 to 500 pmol/L is associated with a lower mortality risk. Owing to its observational design, causality cannot be inferred. Dynamic monitoring of vitamin B12 levels may help identify individuals at increased risk; however, further studies are needed to establish causality.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.