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Prevalence of Functional Cobalamin Deficiency and Relevant Mortality Risk in the General Population: An Unheeded
Yan Liu1,2,3, Yi Gao3, Yige Liu1,2
1Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Insights
Functional cobalamin (Cbl) deficiency, defined by elevated Cbl and methylmalonic acid levels, affects 4.5% of US adults and significantly increases mortality risk. Unlike Cbl deficiency, functional Cbl deficiency is not mitigated by Cbl supplementation.
Area of Science:
- Nutritional Science
- Epidemiology
- Gerontology
Background:
- Current guidelines inadequately address functional cobalamin (Cbl) deficiency, a state of decreased Cbl sensitivity.
- This study investigates the prevalence and mortality associations of functional Cbl deficiency in US adults.
Purpose of the Study:
- To determine the prevalence of functional Cbl deficiency in the US adult population.
- To compare the mortality risk associated with functional Cbl deficiency versus Cbl deficiency.
Main Methods:
- A cohort study of 22,513 US adults (aged ≥20 years) from 1999-2014 with follow-up through 2019.
- Functional Cbl deficiency defined as elevated methylmalonic acid (MMA) and Cbl levels (MMA >250 nmol/L, Cbl >400 pg/mL).
- Cbl deficiency defined as serum Cbl <148 pmol/L (200 pg/mL).
Main Results:
- Functional Cbl deficiency prevalence was 4.5% (approx. 10 million adults), compared to 2.1% for Cbl deficiency.
- The functional Cbl deficiency group (MMAhighCblhigh) showed significantly higher all-cause (HR 1.76) and cardiovascular mortality (HR 2.17) versus the MMAlowCbllow group.
- Mortality risk associated with Cbl deficiency was not significant after confounder adjustment.
Conclusions:
- Functional Cbl deficiency is more prevalent than Cbl deficiency and poses a significant mortality risk.
- Cbl supplementation or increased intake does not appear to reduce the prevalence or mortality risk of functional Cbl deficiency.
Background:
Current guidelines prioritize monitoring and managing cobalamin (Cbl) deficiency but insufficiently address the issue of functional Cbl deficiency (decreased Cbl sensitivity). This study aims to investigate the prevalence burden of functional Cbl deficiency and to examine its prospective association with mortality risk, compared to Cbl deficiency, among United States (US) adults.
Method:
The cohort study included 22,513 US participants aged ≥20 years from 1999 to 2014 and was followed up through December 31, 2019. Cbl sensitivity was assessed using a combination of binary classifications for Cbl and methylmalonic acid (MMA) levels, with cutoff values set at 400 pg/mL for Cbl and 250 nmol/L for MMA. Functional Cbl deficiency was defined as elevated MMA and Cbl levels. Serum Cbl levels <148 pmol/L (200 pg/mL) were classified as Cbl deficiency.
Results:
In this study, approximately 2.1% of US adults had Cbl deficiency, while the age-adjusted prevalence of functional Cbl deficiency was 4.5%, corresponding to an estimated 10 million US adults. Over a median follow-up period of 10.7 years, there were 4636 recorded deaths. Compared to the MMAlowCbllow group (MMA ≤250 nmol/L, Cbl ≤400 pg/mL), the multivariable-adjusted hazard ratios for all-cause, cardiovascular, and cancer-related mortality in the MMAhighCblhigh group were 1.76 (95% confidence interval [CI]: 1.53-2.02, p < 0.001), 2.17 (95% CI: 1.78-2.67, p < 0.001), and 1.38 (95% CI: 0.95-2.00, p = 0.089). In contrast, the mortality risk associated with Cbl deficiency became insignificant after adjusting for similar confounders. While Cbl supplementation or dietary intake above recommended levels might alleviate Cbl deficiency, they do not appear to reduce the prevalence of functional Cbl deficiency or its associated mortality risk.
Conclusion:
Compared with Cbl deficiency, functional Cbl deficiency is more frequent and is significantly associated with increased mortality risk in the general population.
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