A Causal Relationship between Vitamin C Intake with Hyperglycemia and Metabolic Syndrome Risk: A Two-Sample Mendelian Randomization Study

Abstract

Excessive oxidative stress can contribute to metabolic syndrome (MetS), and antioxidants can protect against its development. Vitamin C (VC) is a well-known antioxidant, and observational studies have associated a deficiency with an increased MetS risk. This study tested the hypothesis that dietary VC intake caused an inverse relation of MetS and its components risk using a two-sample Mendelian randomization (MR) method in adults ≥40 years in a city hospital-based (n = 58,701) and Ansan/Ansung plus rural (n = 13,598) cohorts. Independent genetic variants associated with dietary VC intake were explored using a genome-wide association study (GWAS) with significance levels of p < 5 × 10−5 and linkage disequilibrium (r2 threshold of 0.001), after adjusting for the covariates related to MetS, in a city hospital-based cohort (n = 52,676) excluding the participants having vitamin supplementation. MR methods, including inverse-variance weighting (IVW), weighted median, MR-Egger, and weighted model, were used to determine the causal relationship between the dietary VC intake and the risk of MetS and its components in Ansan/Ansung plus rural cohorts (n = 11,733). Heterogeneity and leave-one-out sensitivity analyses were conducted. Energy intake, as well as other nutrient intakes, were significantly lower in the low VC intake group than in the high VC intake group, but the incidence of MetS and its components, including hyperglycemia, hypertriglyceridemia, and hypertension, was observationally higher in inadequate low VC intake in the combined cohorts. In MR analysis, insufficient dietary VC intake increased the risk of MetS, hyperglycemia, hypertriglyceridemia, and hypertension in an IVW (p < 0.05). In contrast, only the serum fasting blood glucose concentration was significantly associated with VC intake in weight median analysis (p < 0.05), but there was no significant association of low dietary VC with MetS and its components in MR-Egger. There was no likelihood of heterogeneity and horizontal pleiotropy in MetS and its components. A single genetic variant did not affect their association in the leave-one-out sensitivity analysis. In conclusion, insufficient dietary VC intake potentially increased the MetS and hyperglycemia risk in Asian adults. Low VC intake can contribute to increasing type 2 diabetes incidence in Asians.

Translational Research on Bee Pollen as a Source of Nutrients: A Scoping Review from Bench to Real World

“…A countless number of studies unveiling the antidiabetic properties, including early preventive, disease course modifying, and complication limiting effects, of individual nutrients and phytochemicals that are ubiquitously present in BP from different botanical and geographical origins have been published so far. This includes, for example, nutrients including vitamins such as groups B [ 241 , 242 , 243 ], C [ 244 , 245 , 246 ], D [ 247 , 248 , 249 ], and E [ 128 , 250 , 251 ], oligo-elements and other minerals [ 252 , 253 , 254 ], and lipids such as unsaturated fatty acids [ 255 , 256 , 257 ] and phytosterols [ 63 , 258 , 259 ], as well as other phytochemicals including polyphenols such as phenolic acids, flavonoids, and stilbenes (very recent and comprehensive reviews of preclinical and clinical evidence can be found in [ 260 , 261 , 262 , 263 , 264 , 265 , 266 ]). Despite the substantial amount of experimental and clinical evidence of all these BP compounds in the complex pathophysiology of diabetes and in its interaction with other comorbidities, the possible synergistic potential and real clinical outcome of these compounds, which are always combined in BP, have generally been omitted in research and must be further studied by in vivo experiments, and subsequently verified and objectively assessed by clinical studies.…”

Genetic and Lifestyle-Related Factors Influencing Serum Hyper-Propionylcarnitine Concentrations and Their Association with Metabolic Syndrome and Cardiovascular Disease Risk

“…(2) Both serum BCAA concentrations and BCAA intake were measured to show their relationship with serum propionylcarnitine concentrations and the genetic impact. (3) The study explored the interaction between genetics and dietary patterns and the influence of smoking on serum propionylcarnitine concentrations. This novel approach adds to our understanding of the complex genetic and lifestyle factors affecting serum propionylcarnitine concentrations.…”

“…MetS is a prevalent and concerning health condition with a significant global impact, and its incidence has been on the rise over recent decades [1]. Although the precise etiology of MetS remains incompletely understood, it is widely recognized that a combination of genetic, lifestyle, and environmental factors contributes to its development [2,3].…”

The Role of Natural Antioxidant Products That Optimize Redox Status in the Prevention and Management of Type 2 Diabetes

“…Vitamin C is a water-soluble antioxidant present in plasma and tissues. As detailed below, vitamin C status and vitamin C supplementation play potential roles in T2D progression and management [ 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ]. The molecular mechanisms for the protective effects of vitamin C on T2D are not fully understood but inhibition of mitochondrial OxS is a probable candidate (see Figure 4 ).…”

“…An increasing body of literature suggests that AA supplementation plays a potential role in the management of T2D [ 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. A 2021 meta-analysis by Mason et al [ 80 ] shows that supplementation with AA decreases HbA1c, fasting glucose, and PPG.…”