Circulating Alpha-Tocopherol Levels, Bone Mineral Density, and Fracture: Mendelian Randomization Study
Karl Michaëlsson1, Susanna C Larsson1,2
1Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
Nutrients
|July 2, 2021
Summary
Higher levels of the antioxidant alpha-tocopherol (Vitamin E) are linked to increased bone mineral density. This study suggests a causal relationship, but found no significant association with fracture risk.
Area of Science:
- Nutritional Science
- Bone Biology
- Genetic Epidemiology
Background:
- Observational studies suggest alpha-tocopherol (Vitamin E) may reduce bone loss and fracture risk.
- The causal relationship between circulating alpha-tocopherol and bone health remains unclear.
Purpose of the Study:
- To investigate the causal associations between circulating alpha-tocopherol levels and estimated bone mineral density (eBMD) and fracture risk.
- Utilizing Mendelian randomization to assess these relationships.
Main Methods:
- Employed Mendelian randomization using three genetic variants strongly associated with alpha-tocopherol levels.
- Analyzed summary-level data from UK Biobank for eBMD (n=426,824) and fracture (n=53,184 cases).
- Used inverse-variance weighted analysis to estimate effects.
Main Results:
- A genetically predicted increase in circulating alpha-tocopherol was associated with a significant increase in eBMD (0.07 g/cm² per SD increase).
- This increase in eBMD corresponds to over 10% higher bone density.
- No significant association was found between genetically predicted alpha-tocopherol and the odds of any fracture.
Conclusions:
- Results provide strong evidence for a causal link between higher circulating alpha-tocopherol and greater bone mineral density.
- Further research, including intervention studies and Mendelian randomization focusing on fragility fractures, is warranted.
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