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Objectives <p>To evaluate the joint, nonlinear, and interactive associations between multiple serum vitamins and cardiovascular disease (CVD), addressing the limitations of prior single-nutrient studies.</p> Methods <p>Using nationally representative adults from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (<i>n</i> = 3055), we adjusted for potential confounders and applied complementary, advanced mixture-modeling techniques—multivariable logistic regression, adaptive elastic net with environmental risk score (AENET–ERS), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR)—to assess component-specific and mixture effects, variable contributions, nonlinearity, and interactions.</p> Results <p>In the NHANES 2005–2006 adult sample, advanced mixture modeling was used to assess the association between vitamin mixtures and CVD. In fully adjusted logistic models, per log-unit increases in vitamins C, D, and E were associated with lower CVD risk, and quartile (Q4 vs Q1) analyses were directionally consistent; vitamins A and B6 were not significant, and B12 showed inconsistent associations. Qgcomp indicated an overall protective mixture effect (per one-quantile increase, logRR − 0.231; RR ≈ 0.79; 95% CI 0.68–0.92), with risk weights primarily from B6 (0.594) and A (0.406) and protective weights from D (− 0.375), C (− 0.359), and E (− 0.251); B12 contributed minimally (− 0.014). AENET–ERS retained E, D, C, B6, and A (β: − 0.219, − 0.204, − 0.204, + 0.195, + 0.179; B12 excluded), while BKMR posterior inclusion probabilities (PIPs) were highest for E (0.943) and D (0.936), followed by B6 (0.857), A (0.796), C (0.735), and B12 (0.437), revealing nonlinear overall protective effects and suggesting that vitamin D modifies the B6–CVD association.</p> Conclusions <p>The vitamin mixture shows an overall protective effect associated with lower CVD risk; contributions are primarily driven by vitamins C, D, and E, with A and B6 contributing risk and B12 playing a minimal role, and there is exploratory evidence of a D × B6 interaction.</p>

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Nonlinear associations between serum vitamin mixtures and cardiovascular disease risk: insights from a national cross-sectional analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月8日

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  • Menglin Tian,
  • Jilei Zhang,
  • Chaoliang Nian,
  • MengTing Wei,
  • Wenzhang Kuang,
  • Wenyin Du,
  • Sen Yang,
  • Xiaohua Zhao,
  • Qiwei Liao,
  • Qiang Xue,
  • Fuding Guo

摘要

Objectives

To evaluate the joint, nonlinear, and interactive associations between multiple serum vitamins and cardiovascular disease (CVD), addressing the limitations of prior single-nutrient studies.

Methods

Using nationally representative adults from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n = 3055), we adjusted for potential confounders and applied complementary, advanced mixture-modeling techniques—multivariable logistic regression, adaptive elastic net with environmental risk score (AENET–ERS), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR)—to assess component-specific and mixture effects, variable contributions, nonlinearity, and interactions.

Results

In the NHANES 2005–2006 adult sample, advanced mixture modeling was used to assess the association between vitamin mixtures and CVD. In fully adjusted logistic models, per log-unit increases in vitamins C, D, and E were associated with lower CVD risk, and quartile (Q4 vs Q1) analyses were directionally consistent; vitamins A and B6 were not significant, and B12 showed inconsistent associations. Qgcomp indicated an overall protective mixture effect (per one-quantile increase, logRR − 0.231; RR ≈ 0.79; 95% CI 0.68–0.92), with risk weights primarily from B6 (0.594) and A (0.406) and protective weights from D (− 0.375), C (− 0.359), and E (− 0.251); B12 contributed minimally (− 0.014). AENET–ERS retained E, D, C, B6, and A (β: − 0.219, − 0.204, − 0.204, + 0.195, + 0.179; B12 excluded), while BKMR posterior inclusion probabilities (PIPs) were highest for E (0.943) and D (0.936), followed by B6 (0.857), A (0.796), C (0.735), and B12 (0.437), revealing nonlinear overall protective effects and suggesting that vitamin D modifies the B6–CVD association.

Conclusions

The vitamin mixture shows an overall protective effect associated with lower CVD risk; contributions are primarily driven by vitamins C, D, and E, with A and B6 contributing risk and B12 playing a minimal role, and there is exploratory evidence of a D × B6 interaction.