This study evaluated the effect of multivitamin use on various health outcomes, including all-cause mortality, liver-related mortality, major vascular events, and CKD in individuals with MASLD and those without steatotic liver disease (No SLD). Using data from the UK Biobank, we found that multivitamin users experienced significantly lower risks of CVD and CKD, with the most prominent protective link observed in individuals with MASLD. These findings contributed to providing evidences suggesting that certain dietary supplements, particularly multivitamins, might have beneficial effects on health, especially in populations with underlying metabolic disorders such as MASLD.

One of the key findings from the present study is the significant reduction in all-cause mortality observed in multivitamin users within the MASLD cohort. Although the overall cohort showed a trend toward reduced mortality among multivitamin users, the effect was more prominent in individuals with MASLD. These data suggest that multivitamins might exert more substantial protective effects in populations with metabolic dysfunction. MASLD is characterized by an increased burden of oxidative stress, inflammation, and insulin resistance, all of which contribute to disease progression^13,14,15. Multivitamins, particularly those containing antioxidants such as vitamins D and E, may interrupt these pathogenic mechanisms, thereby reducing mortality risk^16,17,18.

Previous studies have reported controversial results on the association between multivitamin use and mortality in the general population. For instance, large cohort studies such as the Physicians’ Health Study II and the Women’s Health Initiative found no clear benefit of multivitamin use on cardiovascular events and malignancies^19,20. Nevertheless, our study suggests that individuals with MASLD might represent a distinct population in which multivitamins could be linked to lower risks. This result is consistent with previous research highlighting the role of antioxidants in reducing oxidative stress and inflammation, both of which are central to the pathogenesis of MASLD. In particular, Vitamin E has been shown to improve liver histology in patients with steatohepatitis, a more advanced form of MASLD, by reducing liver inflammation and oxidative damage^21,22​.

Vitamin deficiencies, particularly of vitamins C, D, and E, are commonly observed in patients with type 2 diabetes and cardiometabolic diseases, and are associated with increased oxidative stress, endothelial dysfunction, and chronic inflammation. These micronutrients play critical roles in modulating gene expression and signal transduction pathways that contribute to anti-inflammatory, antioxidant, and hypolipidemic effects²³. In the context of MASLD, where metabolic dysfunction and systemic inflammation are prominent, multivitamin supplementation might provide targeted benefits by attenuating these pathogenic processes. Our study demonstrated that multivitamin use was associated with reduced risks of CVD and CKD, particularly in individuals with MASLD, suggesting that improvements in micronutrient status could translate into significant clinical outcomes.

Furthermore, vitamin D, another key component of multivitamin formulations, is known to play a crucial role in regulating immune function and modulating inflammation^24,25. Vitamin D deficiency has been linked to worse outcomes in individuals with metabolic diseases, including MASLD, due to its role in reducing pro-inflammatory cytokine production and enhancing insulin sensitivity^26,27,28. Vitamin D deficiency has been strongly associated with the progression of CKD, and supplementation may help slow kidney function decline, particularly in individuals with MASLD who are at increased risk of renal complications due to metabolic dysfunction²⁹. Additionally, the antioxidant properties of vitamins C and E may help reduce renal oxidative stress and inflammation, thereby preserving kidney function and reducing the incidence of CKD in high-risk populations³⁰. Therefore, the observed reduction in all-cause mortality in MASLD patients who use multivitamins may reflect the combined impact of these vitamins on reducing the systemic inflammatory and metabolic burden associated with MASLD. Collectively, vitamin D has established immunomodulatory and anti-inflammatory effects, which are particularly relevant in metabolic diseases such as MASLD and CKD.

Our findings also demonstrated a significant reduction in the risk of CVD in multivitamin users across all cohorts, with the greatest effect shown in the MASLD group. CVD, including both cardiovascular and cerebrovascular events, is a major complication in individuals with metabolic disorders like MASLD, where insulin resistance, dyslipidemia, and chronic inflammation contribute to increased vascular risk^31,32. The protective effect of multivitamins including vitamin A, B, C, D, and E, on CVD may be attributed to several factors, including the antioxidant properties of vitamins, their ability to improve endothelial function, and their role in modulating blood pressure and lipid levels^33,34,35,36.

In particular, vitamins such as C and E are potent antioxidants that can reduce oxidative stress, a major contributor to vascular dysfunction in metabolic diseases³⁷. Oxidative stress damages endothelial cells, promotes atherosclerosis, and impairs vascular reactivity, all of which increase the risk of cardiovascular events³⁸. By reducing oxidative damage, multivitamins might help preserve vascular integrity and reduce the incidence of both cardiovascular and cerebrovascular events. Although previous studies suggest that vitamins C and E may contribute to improved endothelial function and vascular health, the direct impact of multivitamin supplementation on CVD risk in MASLD remains speculative and requires further investigation^37,38.

In addition to the observed reduction in CVD, our study found that multivitamin use was associated with a significantly lower incidence of CKD across all cohorts, particularly in the MASLD group. CKD is a common comorbidity in individuals with metabolic disorders, and the progression of both CKD and MASLD is driven by similar etiologies, including hypertension, type 2 diabetes, chronic inflammatory state and dyslipidemia³⁹. The reduction in CKD risk among multivitamin users would reflect the role of specific vitamins, such as D and E, in modulating these pathogenic processes. Vitamin D deficiency has been strongly associated with the progression of CKD, and supplementation may help slow kidney function decline, particularly in individuals with MASLD who are at increased risk of renal complications due to metabolic dysfunction²⁹. Additionally, the antioxidant properties of vitamins C and E may help reduce renal oxidative stress and inflammation, thereby preserving kidney function and reducing the incidence of CKD in high-risk populations³⁰.

Although the observed effect sizes of multivitamin use on MASLD-related outcomes were modest (HRs ranging from 0.7 to 0.9), even small risk reductions could have significant clinical and public health implications. Given the increasing global burden of MASLD and its associated complications, interventions with even modest protective effects might be valuable. Multivitamins are widely used, and their potential health benefits extend beyond liver-related outcomes. Our findings contribute to the broader discussion on preventive strategies for metabolic and liver diseases. Future studies, particularly randomized controlled trials, are required to elucidate the role of multivitamin supplementation in individuals with MASLD.

The strengths of this study include the use of a large, well-characterized cohort from the UK Biobank, which provided robust data on participants’ health, lifestyle, and clinical outcomes. The application of IPTW to control for confounding factors also strengthens the validity of our findings, allowing for more accurate estimates of the effects of multivitamin use. However, there are several limitations. First, multivitamin use was self-reported, which could introduce recall bias or inaccuracies regarding the frequency and duration of supplementation. Additionally, we could not specify formulations of multivitamins used by participants, which would differ in their composition and effects. Furthermore, the observational nature of the study means that we cannot infer causality, and residual confounding by unmeasured factors may still be present. In addition, despite the application of IPTW to balance measured confounders, residual confounding due to unmeasured health-related behaviors, such as diet quality, physical activity, and healthcare utilization, might still influence the observed associations, representing a potential healthy user bias. Moreover, the reliance on self-reported multivitamin use at baseline does not capture long-term adherence, as the UK Biobank lacks longitudinal data on supplement consumption. Notably, although the UK Biobank recruited participants from the general population, the voluntary nature of enrollment may have led to a cohort that is healthier and more health-conscious than the broader population, potentially introducing selection bias. Lastly, the UK Biobank cohort is predominantly of European ancestry, limiting the generalizability of our findings to more diverse ethnicity.