The impact of plasma vitamin C levels on the risk of cardiovascular diseases and Alzheimer's disease: A Mendelian randomization study

Abstract

Background & aims: Previous observational studies have reported associations between plasma vitamin C levels, and cardiovascular diseases (CVDs) and Alzheimer's disease (AD); however, no conclusive results have been obtained. We conducted a Mendelian randomization (MR) study to investigate the causality of vitamin C on the risk of nine CVDs [including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes] and Alzheimer's disease. Methods: Eleven single-nucleotide polymorphisms (SNPs) identified in a recent genome-wide metaanalysis (N ¼ 52,018) were used as the instrumental variables for plasma vitamin C levels. The summarylevel data for CVDs and AD were extracted from consortia and genome-wide association studies (GWAS). We performed MR analyses using the fixed-effects inverse-variance-weighted (IVW) method, weighted median, and MR-Egger approaches.Results: This MR study found suggestive evidence that genetic liability to higher vitamin C levels was associated with a lower risk of cardioembolic stroke [odds ratio (OR, presented per 1 standard deviation increase in plasma vitamin C levels) ¼ 0.773; 95% confidence interval (CI), 0.623e0.959; P ¼ 0.020] and AD (OR ¼ 0.968; 95% CI, 0.946e0.991; P ¼ 0.007) using the fixed-effects IVW method. Sensitivity analysis yielded directionally similar results. A null-association was observed between vitamin C and the other CVDs. Conclusion: Our MR study provided suggestive evidence that higher vitamin C levels were casually associated with a decreased risk of cardioembolic stroke and AD. No evidence was observed to suggest that vitamin C affected the risk of CAD, MI, AF, HF, stroke, IS, large artery stroke, or small vessel stroke. However, well-designed studies are warranted to confirm these results and determine the underlying mechanisms of the causal links.

Vegetable intake and metabolic risk factors: A Mendelian randomization study

“…Previous MR using serum antioxidants as exposures also showed similar results. For example, serum vitamin C was not associated with multiple cardiovascular diseases [44,47,48]; other antioxidants (vitamin E, carotene, lycopene and retinol) were not associated with risk of ischemic stroke [49] and CHD [50].…”

A Mild Causal Relationship Between Tea Consumption and Obesity in General Population: A Two-Sample Mendelian Randomization Study

“…Finally, F statistics ( Eq. (1) ) were used to test the strength of the association between the SNPs as instrumental variables and tea consumption, and an F statistic >10 indicates a lower risk of weak instrumental variable bias ( Zhang Q. et al, 2021 ; Chen et al, 2021 ). N represents the sample size; eaf represents effect allele frequency.…”

Genome-Wide Studies in Ischaemic Stroke: Are Genetics Only Useful for Finding Genes?

“…Perhaps the most interesting studies are those assessing causality using blood biomolecules as these are easy biomarkers to capture for stroke risk assessment but can also be potential drug targets. Not all the studies to date have observed causal associations with stroke risk, in either direction (inflammatory biomarkers [ 76 , 77 , 79 , 83 ], between circulating cytokines [ 96 ], vitamins [ 78 , 79 , 80 , 81 , 82 , 83 , 114 ], and many polyunsaturated fatty acids [ 70 ]). Some interesting findings are: (1) the identification of a causal link between lower serum MMP-12 levels and the risk of AIS, lower serum MMP-1 and MMP-12 levels and the risk of LAS, and higher serum MMP-8 levels and the risk of SVS [ 94 ]; (2) genetically determined levels of hemostatic factors have also been associated with the risk of IS [ 87 , 88 ]; (3) iron factors are causally associated with an increased risk of IS and CES, except transferrin, which is protective against IS and CES [ 73 ]; (4) among the cytokines studied, monocyte chemoattractant protein-1 (MCP-1) is the only one that was associated with an increased risk of IS, LAS, and CES [ 96 ].…”