Osteoarthritis (OA) is a prevalent joint disorder characterized by clinical symptoms such as chronic pain, crepitus, joint stiffness, and structural changes including radiographic alterations and joint-wide tissue degradation (1). The socioeconomic influences of OA are globally recognized as imposing a staggering long-term burden on both individuals and healthcare systems due to the absence of a curative treatment and need for chronic management (2, 3). The pathogenesis of OA is complex, involving a variety of genetic, lifestyle, and other factors (4), and is not fully understood. Certain lifestyle and health factors are found to be definitive risk factors for OA, such as excessive physical activity, alcohol consumption, smoking, type 2 diabetes, and obesity (5). Current studies have outlined a role of diet on OA progression, although mostly centered on the association between diet and obesity and consequent effects on OA (6, 7), or specific types of diet (8).

Research into the effects of diet on OA has yielded interesting, sometimes conflicting results (6, 9–11). There is good evidence to suggest that certain dietary components such as dietary fiber, lipids, and vitamins have a significant impact on OA progression (12–14). These nutrients may influence key molecular pathways implicated in OA pathogenesis, by changing serum lipid concentrations, expression of inflammatory biomarkers, oxidative stress responses, and the activity of matrix metalloproteinases, among other mechanisms (12, 15). There is a gap in research regarding the comprehensive impact of specific foods on osteoarthritis. This study aims to explore the association between specific food items, including coffee, tea, fruits, dairies, meats, vegetables, and nuts, and osteoarthritis using genetic data from the UK Biobank.

The UK Biobank is an invaluable resource for biomedical research, providing a vast repository of detailed genetic, lifestyle, and health information from around 500,000 participants in the UK (16). This allows multifaceted analysis particularly regarding the associations and risk factors of common health problems such as OA. Of particular significance, the database contains genome-wide association analysis data for various dietary intake preferences. The IEU open GWAS database is a comprehensive platform that integrates genome-wide association study data from various sources. The data for our GWAS study on diet were sourced from the summary data of the most recent UK Biobank GWAS available in the IEU Open GWAS database. Mendelian randomization (MR) is an analytical method that conducts causal inferences by using ancestral genetic variations as instrumental variables for exposures (such as dietary preference for milk) and outcomes (such as OA) (17). It takes advantage of the fact that single nucleotide polymorphisms (SNPs) are randomly allocated at conception, avoiding issues of reverse causality and reducing residual confounding. Mendelian randomization is grounded on three key assumptions: (i) Correlation assumption: A robust correlation exists between SNP and exposure factors (ii) Independence assumption: SNP and confounding factors are independent (iii) Exclusion hypothesis: SNP can solely impact the outcome through exposure factors. In this study, we conducted a two-sample Mendelian analysis to investigate the causal relationship between specific dietary preferences and OA. We selected representative food items as exposures and used OA as the outcome. This approach should allow an accurate assessment of the impact of dietary choices on OA risk. The study findings may enhance the current understanding of how common food items affect OA, and inform the development of more effective dietary strategies for disease prevention and its chronic management, particularly in predisposing populations such as those who are overweight or have had prior joint injury.

Mendelian randomization provides a robust framework to differentiate between correlation and causation, offering more reliable insights compared to conventional observational studies. In this study, we used MR to analyze genetic variants associated with common dietary habits, and inferred the potential causal effects of these dietary items on OA. This research may help inform the development of dietary recommendations and preventive strategies for OA. Interestingly, our findings identified four dietary preferences which may impact OA, namely coffee, peas, watercress, and cheese, where the first two had a promoting effect and the last two an inhibiting effect.

Several studies have pointed to the relationship between coffee and OA (25–27). A cross-sectional study found that consuming more than 7 cups of coffee per day was linked to a higher risk of OA in men, and this risk increased with the amount of coffee consumption (26). A recent review also summarized experimental as well as clinical evidence on the negative effects of caffeine on hyaline cartilage, including its catabolic effects on articular and growth plate cartilage (28). Other studies have suggested an indirect effect of caffeine on the relationship between inflammatory factors and articular cartilage, with caffeine intake being associated with the expression of inflammatory cytokines IL-1 and TNF-α (29).

Pea consumption was found to contribute to OA in our study. Very limited research has explored this association in the literature, with only one study suggesting that alcoholic drinks produced using peas was an independent risk factor for OA (30). It should be noted however that this study set out to investigate the relation of alcohol and specific alcoholic drinks with OA risk, and that high consumption of alcohol itself (>14 standard drinks per week) was significantly associated with incident knee surgery due to OA (30). Further research is needed to determine whether there are specific components in peas that may trigger or enhance molecular pathways leading to OA progression.

Interestingly, our findings suggested an inhibitory effect of watercress on OA, which might be related to several mechanisms. Firstly, watercress contains high levels of beneficial compounds such as isothiocyanates, which have shown strong anti-inflammatory properties (31). This may help reduce inflammation in joint tissues and retard associated pro-inflammatory mechanisms contributing to OA development (32). Secondly, watercress is rich in antioxidants such as vitamin C and beta-carotene, which may counteract the harmful effects of free radicals (31), known to be implicated in the degradation of joint cartilage leading to OA progression (33). Furthermore, the nutrients present in watercress may help protect the integrity of cartilage, maintaining normal cartilage metabolism and inhibiting or slowing catabolic processes (34).

Among dairy products, cheese is naturally nutrient dense and provides high levels of compounds that help maintain bone density and strength, which can be beneficial in OA management especially given the bone weakening associated with OA (35) and the critical role of the subchondral bone in OA (36). Cheese provides a rich source of calcium and is often fortified with vitamin D, both of which are essential for maintaining bone health (37). Some cheeses, especially those made from the milk of grass-fed animals, contain conjugated linoleic acid (CLA), a fatty acid shown to possess anti-inflammatory properties (38). Other cheeses from grass-fed animals can have high levels of omega-3 fatty acids (39), also known for their potent anti-inflammatory properties (40). Both of these compounds may provide benefits in reducing the inflammation involved in the pathogenesis of joint diseases including OA.

In this study, we employed a dual-sample MR approach to investigate potential associations between four specific dietary items and the onset of OA. It is important to acknowledge that certain limitations may exist in our work. Firstly, the observational nature of our study may introduce potential biases, as the establishment of a causative relationship would require randomized controlled trials. Additionally, the genetic instruments used for MR may not fully capture the complexity of dietary influences on OA, considering its multifactorial nature as well as the wide-ranging effects of diet on other factors associated with OA such as exercise, obesity, and co-morbidities including cardiovascular disease (41). Secondly, our findings may have been influenced by unmeasured confounding factors. It only includes a range of genetic markers directly associated with the items investigated in this study. To gain an enhanced and more accurate understanding of the relationship between diet and OA, further studies incorporating a wider array of genetic markers and consideration of environmental factors are necessary, particularly given an emerging understanding of the role of epigenetics in OA progression (42). Ideally, these studies should involve diverse populations to comprehend the intricate interplay among genetics, diet, and lifestyle factors in the context of OA. Due to the utilization of summary GWAS data, the demographic information is restricted, with the population solely reflecting individuals of European descent. Consequently, the generalization of the research findings is constrained. In an investigation into the correlation between 21 dietary intakes and osteoarthritis, our study employed Mendelian randomization to evaluate causality, using p-values for statistical significance. Despite its innovative approach, this methodology encounters challenges when dealing with multiple comparisons, especially given the numerous dietary factors involved, which increases the risk of Type I errors. The absence of adjustments for these multiple comparisons represents a notable limitation of our study, underscoring the need for cautious interpretation of our results. Nevertheless, our findings offer valuable insights into the link between diet and osteoarthritis. Future research should consider incorporating correction methods like the Bonferroni or Benjamini-Hochberg procedures to improve result reliability and explore alternative statistical techniques, such as Bayesian approaches, to more precisely evaluate the genuine relationship between diet and osteoarthritis while addressing the issue of multiple comparisons. Moreover, relaxing the threshold for selecting SNPs related to certain dietary items due to a limited number of SNPs meeting the stringent genome-wide significance level may introduce bias and potentially impact the outcomes of our study. Lastly, it is important to note that while the potential mechanisms discussed in this study in relation to the identified food items with significant influence on OA are supported by preliminary research, further studies are necessary to fully understand the extent of the impact of these dietary preferences on OA.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

LC: Formal analysis, Methodology, Writing – original draft, Writing – review & editing. YS: Formal analysis, Methodology, Writing – review & editing. HL: Methodology, Writing – review & editing. ZY: Methodology, Writing – review & editing. JL: Writing – review & editing. DX: Funding acquisition, Methodology, Supervision, Writing – review & editing.