Effect of vegetable and fruit intake on fracture risk: a two-sample Mendelian randomization study

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This study intended to examine the causal relationship between vegetable and fruit intake and fracture risk. Methods The causal correlation was evaluated by a two-sample Mendelian randomization (MR) study. Genetic variation associated with fruit and vegetable intake (dried fruit intake, fresh fruit intake, salad/raw vegetable intake, cooked vegetable intake) and fracture were utilized as instrumental variables in the analysis. The results of inverse-variance weighted (IVW) were used as the basis for the main causal inference and described as odds ratio and 95% confidence interval [OR (95%CI)]. Results Genetically predicted dried fruit intake reduced the risk of fracture of foot (except ankle) [OR = 0.495 (0.252–0.976); P = 0.0423] and fracture of lumbar spine and pelvis [OR = 0.441 (0.208–0.938); P = 0.0334], whereas salad/raw vegetable intake reduced the risk of postmenopausal osteoporosis with pathological fracture [OR = 0.024 (0.001–0.630); P = 0.0253] and fracture of foot (except ankle) [OR = 0.204 (0.052–0.797); P = 0.0223]. However, no relationship was observed between fresh fruit intake and cooked vegetable intake and fracture risk (all P > 0.05). Conclusion Our results reveal a causal correlation between dried fruit and raw vegetable intake and the risk of specific types of fractures. Vegetable and fruit intake fracture causal relationship dried fruits raw vegetables Figures Figure 1 Figure 2 Figure 3 Introduction Fractures due to osteoporosis are a global public health problem, resulting in a significant economic burden [ 1 , 2 ]. The global report on fractures shows that there were an estimated 178 million new fractures and 455 million patients affected by fracture symptoms worldwide in 2019, with the incidence of fractures increasing at all sites in the elderly population [ 3 ]. Fractures can lead to premature death and reduced quality of life [ 4 , 5 ], and the social burden of osteoporosis and fractures is increasing as the population ages. Therefore, identifying potential factors that affect fracture risk is of great value for disease prevention and burden reduction. Dietary factors play a role in maintaining bone health [ 6 ]. Fruits and vegetables are rich in dietary fiber, vitamins, minerals, and phytochemicals, and their intake levels have been reported to be correlated with bone health [ 7 , 8 ]. Fruit and vegetable intake may be related to reduced serum bone resorption markers and elevated bone formation markers [ 9 ]. Cohort studies have reported that increased fruit and vegetable intake was significantly correlated with a reduced risk of hip fracture in both men and women [ 10 , 11 ]. Fruits and vegetables differ in their nutrient composition, and their effects on the human body may also differ due to differences in nutrient content, bioavailability, and digestibility between raw and cooked vegetables and fresh and dried fruits. The Prospective Urban Rural Epidemiology-based study found that raw vegetable intake, rather than cooked vegetable intake, was strongly related to a lower risk of overall mortality [ 12 ]. Some studies have also found that dried fruits may have a bone protective effect, but no consistent conclusions have been reached [ 13 – 15 ]. Mendelian randomization (MR) is a method that uses genetic variation linked to exposure and outcome as an instrumental variable to explore causal relationships [ 16 ]. Several recent studies have reported the application of MR to the etiologic exploration of osteoporosis and fractures [ 17 , 18 ]. Thus, this study intended to assess the causal correlation between the intake of raw and cooked vegetables, fresh and dried fruits and fracture risk through an MR study. Methods Study design and data source The causal link between fruit and vegetable intake and fracture was assessed through a two-sample MR analysis. Genetic variation of single-nucleotide polymorphisms (SNPs) linked to fruit and vegetable intake and fracture were utilized as instrumental variables in MR analysis. When SNPs are applied to MR analysis, three assumptions should be met: (1) SNPs are closely correlated with fruit and vegetable intake; (2) SNPs are independent of the confounders in the correlation between fruit and vegetable intake and fracture; (3) SNPs affect fracture only via fruit and vegetable intake (Figure 1). The SNPs data used in this study were derived from the MRC-IEU database (https://gwas.mrcieu.ac.uk/about/), a publicly genome-wide association studies (GWAS) summary database. Because we used publicly available de-identified data, this study was exempt from ethical review board approval. SNPs for exposure and outcome Fruit and vegetable intake (dried fruit, fresh fruit, salad/raw vegetable, cooked vegetable) were utilized as exposure variables. Data on SNPs correlated with fruit and vegetable intake were derived from the MRC-IEU database, the original source of which is the UKB database (https://www.ukbiobank.ac.uk/), which contains SNP data on dried fruit intake for 421,764 Europeans, SNP data on fresh fruit intake for 446,462 Europeans, SNP data on salad/raw vegetable intake for 435,435 Europeans, and SNP data on cooked vegetable intake for 448,651 Europeans. Fracture (multiple types of fractures) was used as outcome variable. The original source of SNPs associated with the outcome variables was the FinnGEN database (https://r7.finngen.fi/). The sample sizes of patients included in the analyses of the different outcome variables were as follows: osteoporosis (cases/controls: 3,203/209,575), osteoporosis with pathological fracture (cases/controls: 785/172,834), postmenopausal osteoporosis with pathological fracture (cases/controls: 621/122,861), fracture at wrist and hand level (cases/controls: 5,677/199,036), fracture of femur (cases/controls: 3,983/211,460), fracture of foot (except ankle) (cases/controls: 3,515/206,804), fracture of forearm (cases/controls: 9,956/205,768), fracture of lower leg (including ankle) (cases/controls: 10,489/191,178), fracture of lumbar spine and pelvis (cases/controls: 2,859/212,839), fracture of neck (cases/controls: 664/215,476), fracture of rib(s), sternum and thoracic spine (cases/controls: 4,070/211,861), fracture of shoulder and upper arm (cases/controls: 5,824/202,866), and fracture of skull and facial bones (cases/controls: 3,467/196,254). Detailed sources of SNPs correlated with fruit and vegetable intake and fracture are summarized in Supplement Table 1. Selection of instrumental variables SNPs linked to fruit and vegetable intake and fracture undergo a series of screenings before they can be used as instrumental variables in MR analysis. The SNPs linked to fruit and vegetable intake should be significantly associated and remain below the genome-wide statistical significance threshold (5 × 10 -8 ). Second, SNPs with genetic linkage disequilibrium (LD) (clump: r 2 =0.001, 10,000 kb) should be excluded because the presence of LD affects the probability of random assignment of genes. Third, SNPs for being palindromic with intermediate allele frequencies were excluded. The SNPs linked to fruit and vegetable intake were first screened and then the SNPs associated with fracture were harmonized with it by a function in the ‘TwoSampleMR’ software package, so that fruit and vegetable intake and fracture had the same SNPs. Ultimately, the screened SNPs were used as instrumental variables for MR analysis. Statistical analysis Multiple MR analysis methods were applied to explore causal correlations between fruit and vegetable intake and fracture, including inverse-variance weighted (IVW), MR-Egger, weighted-median, and weighted mode. The results of IVW were utilized as the basis for the main causal inference, supplemented by other MR analysis methods. IVW uses a meta-analytical approach to calculate Wald estimates for each SNP to produce an overall estimate of the effect of exposure on outcomes. Therefore, the IVW results for SNPs with heterogeneity were used a random effects model, and the IVW results for SNPs without heterogeneity were used a fixed effects model. To assess the reliability of the correlation between fruit and vegetable intake and fracture, several sensitivity analyses were performed. The strength of instrumental variables was tested using the F-statistic and variance explained (R 2 ), and SNPs with an F-statistic less than 10 were considered weak instrumental variables. The heterogeneity of instrumental variables was assessed by Cochran’s Q statistic of the MR-Egger test and the IVW test, and if the P-value of these tests was less than 0.05, heterogeneity was considered to exist in these SNPs. Horizontal pleiotropy is a genetic variant related to multiple risk factors along different causal pathways, which would violate the basic assumption of MR. The potential horizontal pleiotropy of instrumental variables was examined using the MR-Egger intercept test, and horizontal pleiotropy was considered to exist in these SNPs if the P-value of the test was less than 0.05. The MR Steiger directionality test was used to examine whether the causal link from fruit and vegetable intake to fracture is in the right direction. Furthermore, the leave-one-out analysis was utilized to investigate whether the causal correlation was generated by a single SNP. Statistical analyses were performed by the R (version 4.2.3) software via the TwoSampleMR (version 0.5.7) package. Statistical significance was defined as P-value <0.05. Results Instrumental variables The screening process for SNPs is shown in Supplement Table 2. After screening, the number of SNPs included in the analyses was 41 SNPs related to dried fruit intake, 51 SNPs related to fresh fruit intake, 18 SNPs related to salad/raw vegetable intake, and 17 SNPs related to cooked vegetable intake. The results of the detection of these SNPs are presented in Table 1. The F-statistic for these SNPs in the strength test was much greater than 10, suggesting the absence of weak instrumental variables in these SNPs. The P-values of these SNPs in the horizontal pleiotropy test were all >0.05, indicating that no horizontal pleiotropy was found among these SNPs. Furthermore, the results of the heterogeneity test indicated there was heterogeneity among some SNPs such as the SNPs associated between cooked vegetable intake and postmenopausal osteoporosis with pathological fracture (all P<0.05). Causal link between fruit and vegetable intake and fracture The IVW results on the link between fruit and vegetable intake and fracture risk are listed in Table 2. Genetically predicted dried fruit intake reduced the risk of fracture of foot (except ankle) [OR=0.495 (0.252-0.976); P=0.0423] and fracture of lumbar spine and pelvis [OR=0.441 (0.208-0.938); P=0.0334]. However, no correlation was observed between fresh fruit intake and fracture risk (P>0.05). Genetically predicted salad/raw vegetable intake reduced the risk of postmenopausal osteoporosis with pathological fracture [OR=0.024 (0.001-0.630); P=0.0253] and fracture of foot (except ankle) [OR=0.204 (0.052-0.797); P=0.0223]. Furthermore, there was no relationship between cooked vegetable intake and fracture risk (P>0.05). The results of the other MR methods revealed that the direction of the effect of dried fruit intake and salad/raw vegetable intake on fracture risk remained consistent with IVW (Supplement Table 3). The MR Steiger directionality test showed that the direction of causal association from dried fruit intake and salad/raw vegetable intake to fracture risk was correct (Supplement Table 4). The scatter plots of the links between dried fruit intake and salad/raw vegetable intake and fracture risk are listed in Figure 2. The leave-one-out analysis demonstrated that the causal correlations between dried fruit intake and salad/raw vegetable intake and fracture risk were not generated by any single SNP (Figure 3). Discussion Diet is one of the factors that influence bone quality and fracture risk. We assessed the causal correlation between fruit and vegetable intake and fracture risk. The results indicated that genetically predicted dried fruit intake reduced the risk of fracture of foot (except ankle) and fracture of lumbar spine and pelvis, whereas salad/raw vegetable intake reduced the risk of postmenopausal osteoporosis with pathological fracture and fracture of foot (except ankle). However, no relationship was observed between fresh fruit intake and cooked vegetable intake and fracture risk. Fruit and vegetable intake is an inevitable part of a healthy diet and has been associated with reduced bone loss [ 19 ], bone turnover [ 20 ], and increased bone density [ 21 ]. A cohort study found that subjects who did not consume fruits and vegetables had a significantly higher risk of hip fracture than those who consumed fruits and vegetables daily [ 11 ]. A meta-analysis suggested that increased intake of fruits and vegetables was correlated with a reduced fracture risk [ 22 ]. The current study evaluated the causal correlation between dried and fresh fruit intake, raw and cooked vegetable intake and different fracture risks. However, our study only found a causal correlation between dried fruit intake and salad/raw vegetable intake and fracture risk. Dried fruits are used as storage-resistant alternatives to fresh fruits, and their effects on the human body may be related to their bioavailability and gut microbiota [ 23 ]. The modulation of gut flora by dried fruits reduces chronic inflammation and thus metabolic disorders [ 24 ]. Consumption of dried fruit improves glucose metabolism as well as reduces the risk of osteoporosis [ 23 ]. Several studies have shown that dried plum intake in postmenopausal women increased bone mineral density and reduced bone loss in the subjects [ 14 , 25 ]. Dried fruits such as plums and sultanas have been found to be a source of highly bioavailable phenolics [ 26 ]. For vegetable intake, the cooking process may alter the bioavailability and digestion of nutrients (e.g. vitamins, fibers, and enzymes) in vegetables [ 27 ]. A large prospective cohort study indicated that raw vegetable intake was connected with a lower risk of total mortality, whereas cooked vegetable intake had little benefit in reducing mortality [ 12 ]. This may explain why salad/raw vegetable intake rather than cooked vegetables was connected with a reduced risk of fracture. Bone is a dynamic tissue that is constantly remodeling, and the balance of osteoblasts and osteoclasts plays an important role in bone homeostasis and its remodeling process, as well as in the repair of fractures [ 28 ]. However, the exact mechanisms underlying the effects of dried fruit intake and salad/raw vegetable intake on fracture risk are unclear. Some possible explanations for the lower fracture risk with higher vegetable and fruit intake may be correlated with inflammation, oxidative stress, and acid-base balance in the body. Fruit and vegetable intake was connected with a reduction in chronic inflammation, which has been involved with an increased risk of osteoporosis and fractures [ 29 , 30 ]. Oxidative stress inhibits osteoblast differentiation and there is a relationship between excess reactive oxygen species and bone loss [ 31 ]. Inflammation and oxidative stress may promote bone resorption by enhancing the function of osteoclasts and inhibit bone formation by decreasing the function of osteoblasts [ 32 ]. Fruits and vegetables contain high levels of antioxidants (e.g. carotenoids and ascorbic acid), which may increase osteoblast differentiation and inhibit osteoclast differentiation [ 33 , 34 ]. Other nutrients such as glutathione and polyphenols may also reduce the risk of fracture [ 35 ]. Fruit and vegetable intake slightly alters the acid-base balance, and this mild alkalization increases calcium reabsorption through the renal tubules, thereby reducing bone loss [ 36 ]. Diets rich in fruits and vegetables have a lower dietary acid load, which is associated with inhibiting osteoclast function and promoting osteoblast activity [ 37 ]. Furthermore, fruit and vegetable intake has also been linked to a more diverse gut microbiota, which influences the absorption of minerals such as calcium and has anti-inflammatory effects [ 38 ]. We evaluated the causal link between dried and fresh fruit intake, as well as raw and cooked vegetable intake, and the risk of different types of fractures, which may provide evidence for a causal correlation between fruit and vegetable intake and fracture risk. Nevertheless, this study has some limitations. First, the data for this MR study were from participants of European ancestry, and whether the findings are applicable to other populations needs to be further verified. Second, this study was unable to analyze the non-linear relationship between vegetable and fruit intake and fracture risk due to the lack of individual data. Third, MR methods can only perform causal analysis and cannot explain the mechanism of action between vegetable and fruit intake and fracture risk. Conclusions The causal relationship between dried and fresh fruit intake, as well as raw and cooked vegetable intake, and the risk of different types of fractures was explored. Genetically predicted dried fruit intake reduced the risk of fracture of foot (except ankle) and fracture of lumbar spine and pelvis, whereas salad/raw vegetable intake reduced the risk of postmenopausal osteoporosis with pathological fracture and fracture of foot (except ankle). However, no correlation was found between fresh fruit intake and cooked vegetable intake and fracture risk. Future studies may need to explore the mechanisms by which vegetable and fruit intake contribute to fracture risk. Declarations Ethics statement The requirement of ethical approval for this was waived by the Institutional Review Board of the Affiliated LiHuiLi Hospital of Ningbo University, because this study was a secondary analysis of summary-level data. The need for informed consent was waived. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication Not applicable. Availability of data and materials Data used in this study were derived from the MRC-IEU project (https://gwas.mrcieu.ac.uk/datasets/). Competing interests The authors declare that they have no competing interests. Funding This study was funded by the Social Welfare Research Key Project of Ningbo, China (Grant No. 2021S105), the Natural Science Foundation of Ningbo, China (Grant No. 2022J251, 2022J267), the Medical and Health Research Project of Zhejiang Province (Grant No. 2021429693), and the Ningbo Top Medical and Health Research Program (Grant No. 2022020102). Authors’ contributions Kaifeng Gan and Yanxue Dong designed the study. Yanxue Dong wrote the manuscript. Ke Zhou, Shirong Gu, Leidong Lian, and Zhe Luo collected, analyzed, and interpreted the data. Kaifeng Gan critically reviewed, edited, and approved the manuscript. All authors read and approved the final manuscript. Acknowledgements Clinical trial number:Not applicable. References Compston JE, McClung MR, Leslie WD: Osteoporosis . Lancet (London, England) 2019, 393 (10169):364-376. 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Weaver CM, Dawson-Hughes B, Rizzoli R, Heaney RP: Nutritional Support for Osteoporosis . In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. edn.; 2018: 534-540. Frassetto L, Banerjee T, Powe N, Sebastian A: Acid Balance, Dietary Acid Load, and Bone Effects-A Controversial Subject . Nutrients 2018, 10 (4). Jeffery IB, O'Toole PW: Diet-microbiota interactions and their implications for healthy living . Nutrients 2013, 5 (1):234-252. Tables Table 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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01:53:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9391075/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9391075/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107738525,"identity":"f5020dc8-2d94-4947-b22b-999067319265","added_by":"auto","created_at":"2026-04-24 14:29:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3906958,"visible":true,"origin":"","legend":"\u003cp\u003eThe Mendelian randomization (MR) assumptions of this study.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9391075/v1/96676e3f4f4c50f8862bbbaa.png"},{"id":107738527,"identity":"d8dcda20-7531-443b-81c4-8ebd9d4f1b3d","added_by":"auto","created_at":"2026-04-24 14:29:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1292995,"visible":true,"origin":"","legend":"\u003cp\u003eThe scatter plots of the associations between dried fruit intake and salad/raw vegetable intake and fracture risk.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9391075/v1/f478423bf3f43d8a999de715.png"},{"id":107868979,"identity":"a4ecbe8a-660b-4b11-af05-505a869c3bac","added_by":"auto","created_at":"2026-04-27 07:35:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2000714,"visible":true,"origin":"","legend":"\u003cp\u003eThe leave-one-out analysis of the causal correlations between dried fruit intake and salad/raw vegetable intake and fracture risk.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9391075/v1/22efda546ae3694ded25f963.png"},{"id":109203579,"identity":"697f4648-ef00-4888-9386-e9baaeb31211","added_by":"auto","created_at":"2026-05-13 14:40:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7056341,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9391075/v1/802bcfc1-c53e-4e25-be35-b1c4cb1814a4.pdf"},{"id":107869164,"identity":"3245a19b-e1b6-4506-9f9a-0e2a9f381c86","added_by":"auto","created_at":"2026-04-27 07:36:17","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":29547,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-9391075/v1/db7cd01daca42356168ece06.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of vegetable and fruit intake on fracture risk: a two-sample Mendelian randomization study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFractures due to osteoporosis are a global public health problem, resulting in a significant economic burden [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The global report on fractures shows that there were an estimated 178\u0026nbsp;million new fractures and 455\u0026nbsp;million patients affected by fracture symptoms worldwide in 2019, with the incidence of fractures increasing at all sites in the elderly population [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Fractures can lead to premature death and reduced quality of life [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and the social burden of osteoporosis and fractures is increasing as the population ages. Therefore, identifying potential factors that affect fracture risk is of great value for disease prevention and burden reduction.\u003c/p\u003e \u003cp\u003eDietary factors play a role in maintaining bone health [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Fruits and vegetables are rich in dietary fiber, vitamins, minerals, and phytochemicals, and their intake levels have been reported to be correlated with bone health [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Fruit and vegetable intake may be related to reduced serum bone resorption markers and elevated bone formation markers [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Cohort studies have reported that increased fruit and vegetable intake was significantly correlated with a reduced risk of hip fracture in both men and women [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Fruits and vegetables differ in their nutrient composition, and their effects on the human body may also differ due to differences in nutrient content, bioavailability, and digestibility between raw and cooked vegetables and fresh and dried fruits. The Prospective Urban Rural Epidemiology-based study found that raw vegetable intake, rather than cooked vegetable intake, was strongly related to a lower risk of overall mortality [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Some studies have also found that dried fruits may have a bone protective effect, but no consistent conclusions have been reached [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMendelian randomization (MR) is a method that uses genetic variation linked to exposure and outcome as an instrumental variable to explore causal relationships [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Several recent studies have reported the application of MR to the etiologic exploration of osteoporosis and fractures [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Thus, this study intended to assess the causal correlation between the intake of raw and cooked vegetables, fresh and dried fruits and fracture risk through an MR study.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and data source\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe causal link between fruit and vegetable intake and fracture was assessed through a two-sample MR analysis. Genetic variation of single-nucleotide polymorphisms (SNPs) linked to fruit and vegetable intake and fracture were utilized as instrumental variables in MR analysis. When SNPs are applied to MR analysis, three assumptions should be met: (1) SNPs are closely correlated with fruit and vegetable intake; (2) SNPs are independent of the confounders in the correlation between fruit and vegetable intake and fracture; (3) SNPs affect fracture only via fruit and vegetable intake (Figure 1). The SNPs data used in this study were derived from the MRC-IEU database (https://gwas.mrcieu.ac.uk/about/), a publicly genome-wide association studies (GWAS) summary database. Because we used publicly available de-identified data, this study was exempt from ethical review board approval.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSNPs for exposure and outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFruit and vegetable intake (dried fruit, fresh fruit, salad/raw vegetable, cooked vegetable) were utilized as exposure variables. Data on SNPs correlated with\u0026nbsp;fruit and vegetable intake were derived from the MRC-IEU database, the original source of which is the UKB database (https://www.ukbiobank.ac.uk/), which contains SNP data on dried fruit intake for 421,764 Europeans, SNP data on fresh fruit intake for 446,462\u0026nbsp;Europeans, SNP data on salad/raw vegetable intake for 435,435 Europeans, and SNP data on cooked vegetable intake for 448,651 Europeans.\u003c/p\u003e\n\u003cp\u003eFracture (multiple types of fractures) was used as outcome variable. The original source of SNPs associated with the outcome variables was the FinnGEN database (https://r7.finngen.fi/). The sample sizes of patients included in the analyses of the different outcome variables were as follows: osteoporosis (cases/controls: 3,203/209,575), osteoporosis with pathological fracture (cases/controls: 785/172,834), postmenopausal osteoporosis with pathological fracture (cases/controls: 621/122,861), fracture at wrist and hand level (cases/controls: 5,677/199,036), fracture of femur (cases/controls: 3,983/211,460), fracture of foot (except ankle) (cases/controls: 3,515/206,804), fracture of forearm (cases/controls: 9,956/205,768), fracture of lower leg (including ankle) (cases/controls: 10,489/191,178), fracture of lumbar spine and pelvis (cases/controls: 2,859/212,839), fracture of neck (cases/controls: 664/215,476), fracture of rib(s), sternum and thoracic spine (cases/controls: 4,070/211,861), fracture of shoulder and upper arm (cases/controls: 5,824/202,866), and fracture of skull and facial bones (cases/controls: 3,467/196,254). Detailed sources of SNPs correlated with fruit and vegetable intake and fracture are summarized in Supplement Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSelection of instrumental variables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSNPs linked to fruit and vegetable intake and fracture undergo a series of screenings before they can be used as instrumental variables in MR analysis. The SNPs linked to fruit and vegetable intake should be significantly associated and remain below the genome-wide statistical significance threshold (5 \u0026times; 10\u003csup\u003e-8\u003c/sup\u003e). Second, SNPs with genetic linkage disequilibrium (LD) (clump: r\u003csup\u003e2\u003c/sup\u003e=0.001, 10,000 kb) should be excluded because the presence of LD affects the probability of random assignment of genes. Third, SNPs for being palindromic with intermediate allele frequencies were excluded. The SNPs linked to fruit and vegetable intake were first screened and then the SNPs associated with fracture were harmonized with it by a function in the \u0026lsquo;TwoSampleMR\u0026rsquo; software package, so that fruit and vegetable intake and fracture had the same SNPs. Ultimately, the screened SNPs were used as instrumental variables for MR analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultiple MR analysis methods were applied to explore causal correlations between fruit and vegetable intake and fracture, including inverse-variance weighted (IVW), MR-Egger, weighted-median, and weighted mode. The results of IVW were utilized as the basis for the main causal inference, supplemented by other MR analysis methods. IVW uses a meta-analytical approach to calculate Wald estimates for each SNP to produce an overall estimate of the effect of exposure on outcomes. Therefore, the IVW results for SNPs with heterogeneity were used a random effects model, and the IVW results for SNPs without heterogeneity were used a fixed effects model.\u003c/p\u003e\n\u003cp\u003eTo assess the reliability of the correlation between fruit and vegetable intake and fracture, several sensitivity analyses were performed. The strength of instrumental variables was tested using the F-statistic and variance explained (R\u003csup\u003e2\u003c/sup\u003e), and SNPs with an F-statistic less than 10 were considered weak instrumental variables. The heterogeneity of instrumental variables was assessed by Cochran\u0026rsquo;s Q statistic of the MR-Egger test and the IVW test, and if the P-value of these tests was less than 0.05, heterogeneity was considered to exist in these SNPs. Horizontal pleiotropy is a genetic variant related to multiple risk factors along different causal pathways, which would violate the basic assumption of MR. The potential horizontal pleiotropy of instrumental variables was examined using the MR-Egger intercept test, and horizontal pleiotropy was considered to exist in these SNPs if the P-value of the test was less than 0.05. The MR Steiger directionality test was used to examine whether the causal link from fruit and vegetable intake to fracture is in the right direction. Furthermore, the leave-one-out analysis was utilized to investigate whether the causal correlation was generated by a single SNP. Statistical analyses were performed by the R (version 4.2.3) software via the TwoSampleMR (version 0.5.7) package. Statistical significance was defined as P-value \u0026lt;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eInstrumental variables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe screening process for SNPs is shown in Supplement Table 2. After screening, the number of SNPs included in the analyses was 41 SNPs related to dried fruit intake, 51 SNPs related to fresh fruit intake, 18 SNPs related to salad/raw vegetable intake, and 17 SNPs related to cooked vegetable intake. The results of the detection of these SNPs are presented in Table 1. The F-statistic for these SNPs in the strength test was much greater than 10, suggesting the absence of weak instrumental variables in these SNPs. The P-values of these SNPs in the horizontal pleiotropy test were all \u0026gt;0.05, indicating that no horizontal pleiotropy was found among these SNPs. Furthermore, the results of the heterogeneity test indicated there was heterogeneity among some SNPs such as the SNPs associated between cooked vegetable intake and postmenopausal osteoporosis with pathological fracture (all P\u0026lt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCausal link between fruit and vegetable intake and fracture\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe IVW results on the link between fruit and vegetable intake and fracture risk are listed in Table 2. Genetically predicted dried fruit intake reduced the risk of fracture of foot (except ankle) [OR=0.495 (0.252-0.976); P=0.0423] and fracture of lumbar spine and pelvis [OR=0.441 (0.208-0.938); P=0.0334]. However, no correlation was observed between fresh fruit intake and fracture risk (P\u0026gt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGenetically predicted salad/raw vegetable intake reduced the risk of postmenopausal osteoporosis with pathological fracture [OR=0.024 (0.001-0.630); P=0.0253] and fracture of foot (except ankle) [OR=0.204 (0.052-0.797); P=0.0223]. Furthermore, there was no relationship between cooked vegetable intake and fracture risk (P\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eThe results of the other MR methods revealed that the direction of the effect of dried fruit intake and salad/raw vegetable intake on fracture risk remained consistent with IVW (Supplement Table 3). The MR Steiger directionality test showed that the direction of causal association from dried fruit intake and salad/raw vegetable intake to fracture risk was correct (Supplement Table 4). The scatter plots of the links between dried fruit intake and salad/raw vegetable intake and fracture risk are listed in Figure 2. The leave-one-out analysis demonstrated that the causal correlations between dried fruit intake and salad/raw vegetable intake and fracture risk were not generated by any single SNP (Figure 3).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDiet is one of the factors that influence bone quality and fracture risk. We assessed the causal correlation between fruit and vegetable intake and fracture risk. The results indicated that genetically predicted dried fruit intake reduced the risk of fracture of foot (except ankle) and fracture of lumbar spine and pelvis, whereas salad/raw vegetable intake reduced the risk of postmenopausal osteoporosis with pathological fracture and fracture of foot (except ankle). However, no relationship was observed between fresh fruit intake and cooked vegetable intake and fracture risk.\u003c/p\u003e \u003cp\u003eFruit and vegetable intake is an inevitable part of a healthy diet and has been associated with reduced bone loss [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], bone turnover [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], and increased bone density [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. A cohort study found that subjects who did not consume fruits and vegetables had a significantly higher risk of hip fracture than those who consumed fruits and vegetables daily [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A meta-analysis suggested that increased intake of fruits and vegetables was correlated with a reduced fracture risk [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The current study evaluated the causal correlation between dried and fresh fruit intake, raw and cooked vegetable intake and different fracture risks. However, our study only found a causal correlation between dried fruit intake and salad/raw vegetable intake and fracture risk. Dried fruits are used as storage-resistant alternatives to fresh fruits, and their effects on the human body may be related to their bioavailability and gut microbiota [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The modulation of gut flora by dried fruits reduces chronic inflammation and thus metabolic disorders [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Consumption of dried fruit improves glucose metabolism as well as reduces the risk of osteoporosis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Several studies have shown that dried plum intake in postmenopausal women increased bone mineral density and reduced bone loss in the subjects [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Dried fruits such as plums and sultanas have been found to be a source of highly bioavailable phenolics [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. For vegetable intake, the cooking process may alter the bioavailability and digestion of nutrients (e.g. vitamins, fibers, and enzymes) in vegetables [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A large prospective cohort study indicated that raw vegetable intake was connected with a lower risk of total mortality, whereas cooked vegetable intake had little benefit in reducing mortality [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This may explain why salad/raw vegetable intake rather than cooked vegetables was connected with a reduced risk of fracture.\u003c/p\u003e \u003cp\u003eBone is a dynamic tissue that is constantly remodeling, and the balance of osteoblasts and osteoclasts plays an important role in bone homeostasis and its remodeling process, as well as in the repair of fractures [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, the exact mechanisms underlying the effects of dried fruit intake and salad/raw vegetable intake on fracture risk are unclear. Some possible explanations for the lower fracture risk with higher vegetable and fruit intake may be correlated with inflammation, oxidative stress, and acid-base balance in the body. Fruit and vegetable intake was connected with a reduction in chronic inflammation, which has been involved with an increased risk of osteoporosis and fractures [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Oxidative stress inhibits osteoblast differentiation and there is a relationship between excess reactive oxygen species and bone loss [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Inflammation and oxidative stress may promote bone resorption by enhancing the function of osteoclasts and inhibit bone formation by decreasing the function of osteoblasts [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Fruits and vegetables contain high levels of antioxidants (e.g. carotenoids and ascorbic acid), which may increase osteoblast differentiation and inhibit osteoclast differentiation [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Other nutrients such as glutathione and polyphenols may also reduce the risk of fracture [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Fruit and vegetable intake slightly alters the acid-base balance, and this mild alkalization increases calcium reabsorption through the renal tubules, thereby reducing bone loss [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Diets rich in fruits and vegetables have a lower dietary acid load, which is associated with inhibiting osteoclast function and promoting osteoblast activity [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Furthermore, fruit and vegetable intake has also been linked to a more diverse gut microbiota, which influences the absorption of minerals such as calcium and has anti-inflammatory effects [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe evaluated the causal link between dried and fresh fruit intake, as well as raw and cooked vegetable intake, and the risk of different types of fractures, which may provide evidence for a causal correlation between fruit and vegetable intake and fracture risk. Nevertheless, this study has some limitations. First, the data for this MR study were from participants of European ancestry, and whether the findings are applicable to other populations needs to be further verified. Second, this study was unable to analyze the non-linear relationship between vegetable and fruit intake and fracture risk due to the lack of individual data. Third, MR methods can only perform causal analysis and cannot explain the mechanism of action between vegetable and fruit intake and fracture risk.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe causal relationship between dried and fresh fruit intake, as well as raw and cooked vegetable intake, and the risk of different types of fractures was explored. Genetically predicted dried fruit intake reduced the risk of fracture of foot (except ankle) and fracture of lumbar spine and pelvis, whereas salad/raw vegetable intake reduced the risk of postmenopausal osteoporosis with pathological fracture and fracture of foot (except ankle). However, no correlation was found between fresh fruit intake and cooked vegetable intake and fracture risk. Future studies may need to explore the mechanisms by which vegetable and fruit intake contribute to fracture risk.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe requirement of ethical approval for this was waived by the Institutional Review Board of the Affiliated LiHuiLi Hospital of Ningbo University, because this study was a secondary analysis of summary-level data. The need for informed consent was waived. All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData used in this study were derived from the MRC-IEU project (https://gwas.mrcieu.ac.uk/datasets/).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Social Welfare Research Key Project of Ningbo, China (Grant No. 2021S105), the Natural Science Foundation of Ningbo, China (Grant No. 2022J251, 2022J267), the Medical and Health Research Project of Zhejiang Province (Grant No. 2021429693), and the Ningbo Top Medical and Health Research Program (Grant No. 2022020102).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaifeng Gan and Yanxue Dong designed the study. Yanxue Dong wrote the manuscript. Ke Zhou, Shirong Gu, Leidong Lian, and Zhe Luo collected, analyzed, and interpreted the data. Kaifeng Gan critically reviewed, edited, and approved the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical trial number:Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCompston JE, McClung MR, Leslie WD: \u003cstrong\u003eOsteoporosis\u003c/strong\u003e. \u003cem\u003eLancet (London, England) \u003c/em\u003e2019, \u003cstrong\u003e393\u003c/strong\u003e(10169):364-376.\u003c/li\u003e\n\u003cli\u003eHernlund E, Svedbom A, Iverg\u0026aring;rd M, Compston J, Cooper C, Stenmark J, McCloskey EV, J\u0026ouml;nsson B, Kanis JA: \u003cstrong\u003eOsteoporosis in the European Union: medical management, epidemiology and economic burden. 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In: \u003cem\u003ePrimer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism.\u003c/em\u003e edn.; 2018: 534-540.\u003c/li\u003e\n\u003cli\u003eFrassetto L, Banerjee T, Powe N, Sebastian A: \u003cstrong\u003eAcid Balance, Dietary Acid Load, and Bone Effects-A Controversial Subject\u003c/strong\u003e. \u003cem\u003eNutrients \u003c/em\u003e2018, \u003cstrong\u003e10\u003c/strong\u003e(4).\u003c/li\u003e\n\u003cli\u003eJeffery IB, O\u0026apos;Toole PW: \u003cstrong\u003eDiet-microbiota interactions and their implications for healthy living\u003c/strong\u003e. \u003cem\u003eNutrients \u003c/em\u003e2013, \u003cstrong\u003e5\u003c/strong\u003e(1):234-252.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"food-nutrition-and-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Food, Nutrition and Health](https://link.springer.com/journal/44403)","snPcode":"44403","submissionUrl":"https://submission.springernature.com/new-submission/44403/3","title":"Food, Nutrition and Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Vegetable and fruit intake, fracture, causal relationship, dried fruits, raw vegetables","lastPublishedDoi":"10.21203/rs.3.rs-9391075/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9391075/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eVegetables and fruits are part of a healthy diet. This study intended to examine the causal relationship between vegetable and fruit intake and fracture risk.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe causal correlation was evaluated by a two-sample Mendelian randomization (MR) study. Genetic variation associated with fruit and vegetable intake (dried fruit intake, fresh fruit intake, salad/raw vegetable intake, cooked vegetable intake) and fracture were utilized as instrumental variables in the analysis. The results of inverse-variance weighted (IVW) were used as the basis for the main causal inference and described as odds ratio and 95% confidence interval [OR (95%CI)].\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eGenetically predicted dried fruit intake reduced the risk of fracture of foot (except ankle) [OR\u0026thinsp;=\u0026thinsp;0.495 (0.252\u0026ndash;0.976); P\u0026thinsp;=\u0026thinsp;0.0423] and fracture of lumbar spine and pelvis [OR\u0026thinsp;=\u0026thinsp;0.441 (0.208\u0026ndash;0.938); P\u0026thinsp;=\u0026thinsp;0.0334], whereas salad/raw vegetable intake reduced the risk of postmenopausal osteoporosis with pathological fracture [OR\u0026thinsp;=\u0026thinsp;0.024 (0.001\u0026ndash;0.630); P\u0026thinsp;=\u0026thinsp;0.0253] and fracture of foot (except ankle) [OR\u0026thinsp;=\u0026thinsp;0.204 (0.052\u0026ndash;0.797); P\u0026thinsp;=\u0026thinsp;0.0223]. However, no relationship was observed between fresh fruit intake and cooked vegetable intake and fracture risk (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur results reveal a causal correlation between dried fruit and raw vegetable intake and the risk of specific types of fractures.\u003c/p\u003e","manuscriptTitle":"Effect of vegetable and fruit intake on fracture risk: a two-sample Mendelian randomization study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-24 14:29:08","doi":"10.21203/rs.3.rs-9391075/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-13T08:21:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"33776236284208145427470347143190323777","date":"2026-05-05T14:45:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"131220004559223942031724884003782858951","date":"2026-05-05T09:31:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164678650345468062759245995203509267139","date":"2026-04-23T12:38:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-16T11:34:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-15T10:04:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-15T10:03:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Food, Nutrition and Health","date":"2026-04-12T01:48:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"food-nutrition-and-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Food, Nutrition and Health](https://link.springer.com/journal/44403)","snPcode":"44403","submissionUrl":"https://submission.springernature.com/new-submission/44403/3","title":"Food, Nutrition and Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"905ae3a9-5077-450d-b0bb-76b269a38b5f","owner":[],"postedDate":"April 24th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-13T08:21:47+00:00","index":39,"fulltext":""},{"type":"reviewerAgreed","content":"33776236284208145427470347143190323777","date":"2026-05-05T14:45:47+00:00","index":36,"fulltext":""},{"type":"reviewerAgreed","content":"131220004559223942031724884003782858951","date":"2026-05-05T09:31:35+00:00","index":34,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-24T14:29:09+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-24 14:29:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9391075","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9391075","identity":"rs-9391075","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}