Plasma erythritol levels, cardiovascular risk and overall muscular strength in young male adults – a cluster-based cross-sectional analysis

Abstract

Introduction & Purpose

Erythritol, a commonly used non-nutritive sweetener and endogenous metabolite, has been recently proposed as a possible biomarker of cardiometabolic disease risk (Ortiz & Field, 2020) after its elevated blood concentrations were associated with subsequent gains in body weight, fat, and abdominal adiposity in young adults (Hootman et al, 2017). Simultaneously, muscular strength has been inversely associated with cardiovascular disease (Carbone et al, 2020). As skeletal muscle is a central regulator of glucose homeostasis and muscular insulin resistance can appear decades before the onset of pancreatic β-cell failure or symptoms of type 2 diabetes (Merz & Thurmond, 2020), muscular strength may provide early and important additional information about metabolic health. However, it remains unclear whether plasma erythritol differ between cardiovascular risk profiles in young, healthy individuals before potentially manifesting cardiovascular diseases. Therefore, this study identifies cardiovascular risk profiles using cluster analysis to compare them regarding both erythritol levels and overall muscular strength in young healthy Austrian men.

Methods

This cross-sectional study examined a sample of 339 young male Austrian conscripts (age: 17.9 ± 0,5 years, BMI: 23.8 ± 0.3 kg/m²). Blood parameters and anthropometric data were recorded at the Austrian military draft board. Erythritol concentrations were investigated using targeted metabolomics. Overall muscular strength comprising upper limbs, lower limbs and trunk was measured with the Myoline DIERS device. Cardiovascular risk profiles were developed using cluster analysis based on cardiovascular risk-related parameters, including waist-circumference, systolic blood pressure, triglycerides, HDL-cholesterol and LDL-cholesterol. A two-cluster solution differentiated between a more and a less favorable cardiovascular risk profile. Erythritol concentrations and overall muscular strength were compared according to cluster allocation using Mann-Whitney-U tests. To assess whether muscular strength explained between-cluster difference, rank-transformed ANCOVA was performed.

Results

Cluster analysis identified two differing cardiovascular risk profiles, classified as either a more (n = 239) or less (n = 100) favorable cardiovascular risk profile. In comparison, erythritol levels were significantly higher in the less favorable risk profile (Z = -2.158, p = 0.031, r = 0.118). Overall muscular strength was significantly lower in subjects assigned to the less favorable cardiovascular risk profile compared to subjects in the more favorable cardiovascular risk profile (Z = -2.767, p = 0.006, r = 0.153). In rank-transformed ANCOVA, cluster allocation was significantly associated with erythritol (p = 0.018) as well as overall muscular strength (p = 0.039).

Discussion

According to our findings, participants with a less favorable cardiovascular risk profile tend to have higher erythritol levels and lower overall muscular strength. However, given the small effect sizes, no firm conclusions regarding the clinical or biological relevance can be drawn. Cluster difference in erythritol remained significant after adjustment for overall muscular strength, suggesting that muscular strength did not entirely explain the observed between-cluster difference.

Conclusion

A less favorable cardiovascular risk profile appears to be linked to higher plasma erythritol levels and lower overall muscular strength in young adulthood. Differences in erythritol were not entirely explained by overall muscular strength, highlighting the need for further research regarding individual associations of erythritol and overall muscular strength with cardiovascular risk in young individuals. Furthermore, the sample consisted exclusively of young men, which limits the generalizability of the results to women, other age groups and other population groups.

References

Carbone, S., Kirkman, D. L., Garten, R. S., Rodriguez-Miguelez, P., Artero, E. G., Lee, D. C., & Lavie, C. J. (2020). Muscular Strength and Cardiovascular Disease: AN UPDATED STATE-OF-THE-ART NARRATIVE REVIEW. Journal of cardiopulmonary rehabilitation and prevention, 40(5), 302–309. https://doi.org/10.1097/HCR.0000000000000525

Hootman, K. C., Trezzi, J. P., Kraemer, L., Burwell, L. S., Dong, X., Guertin, K. A., Jaeger, C., Stover, P. J., Hiller, K., & Cassano, P. A. (2017). Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults. Proceedings of the National Academy of Sciences of the United States of America, 114(21), E4233–E4240. https://doi.org/10.1073/pnas.1620079114

Merz, K. E., & Thurmond, D. C. (2020). Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake. Comprehensive Physiology, 10(3), 785–809. https://doi.org/10.1002/cphy.c190029

Ortiz, S. R., & Field, M. S. (2020). Mammalian metabolism of erythritol: a predictive biomarker of metabolic dysfunction. Current opinion in clinical nutrition and metabolic care, 23(5), 296–301. https://doi.org/10.1097/MCO.0000000000000665