Abstract
Background
Gallstones represent a significant global health challenge, impacting both the healthcare system and the broader socio-economic landscape. Despite their prevalence, the relationship between vitamin intake and gallstone development remains underexplored, which this research aims to address.
Methods
A total of 4,628 participants from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) database were included in this study. Data on gallstones were collected through self-reported questionnaires. We conducted a multifactorial logistic regression analysis to explore the association between vitamin intake and the prevalence of gallstones. Various subgroups were analyzed, and potential interactions were tested.
Results
Female gender, advanced age, obesity, and hyperlipidemia were identified as risk factors associated with a higher prevalence of gallstones. Higher dietary intake of vitamin B6 (OR: 0.73, 95% CI 0.61–0.88), niacin (OR: 0.96, 95% CI 0.95–0.98) and vitamin E (OR: 0.96, 95% CI 0.94–0.99) was associated with reduced gallstone risk in unadjusted models. However, after full adjustment (Model 3), only niacin retained marginal significance (OR: 0.98, 95% CI 0.97–1.00, p = 0.035). Restricted cubic spline analyses suggested potential linear relationships between niacin and gallstone risk.
Conclusions
The findings from the NHANES database indicate that increased dietary intake of vitamin B6, niacin, and vitamin E may lower the risk of gallstones in the U.S. population. The mechanisms underlying the role of vitamins in gallstone formation warrant further exploration.
Keywords: Cholelithiasis, Vitamin, Nutrition, NHANES, Diet
Introduction
Gallstones are among the most prevalent digestive disorders worldwide, posing significant social and economic challenges [1–3]. While most gallstones present with mild symptoms and are manageable through medical or surgical interventions, some can lead to severe complications and even become life-threatening [4, 5]. Research has identified several risk factors for gallstones, including gender, age, obesity, and lack of physical activity [6, 7]. In addition, dietary habits are increasingly recognized as crucial in the development of gallstones [8].
Vitamins, essential micronutrients for human life, play a pivotal role in maintaining health. With societal advances, there is a growing emphasis on preventive healthcare, leading to an increase in the daily consumption of vitamin supplements [9, 10]. Research has shown that vitamin intake can both prevent and alleviate the progression of various diseases, such as retinal diseases, neurological disorders and scurvy [11–13]. Although previous studies have shown that in populations with gallstones, the levels of some vitamins such as vitamin B12 and vitamin E are lower than in those without gallstones, suggesting that the levels of certain vitamins in the body may influence the occurrence of gallstones, these studies have generally been limited by small sample sizes, and their conclusions have not been entirely consistent [14, 15].
Consequently, this study aims to perform a cross-sectional analysis using the NHANES database to investigate the correlation between daily vitamin intake and the incidence of gallstones. This study aims to identify any previously unrecognized vitamins that may be linked to gallstones and validate previous findings.
Methods
Data collection
This study used data from the 2017–2020 NHANES, which is overseen by the National Center for Health Statistics (NCHS) and includes demographic details, nutritional surveys, health questionnaires, results from lab tests, and physiological measurements. The data and research materials from NHANES are publicly accessible. The study was conducted with ethical clearance, and every participant gave their written consent.
This study, based on NHANES data, is a cross-sectional analysis designed to explore the link between gallstone occurrence and daily vitamin consumption. Initially, the study encompassed 15,560 participants from 2017 to 2020. We excluded 6350 participants lacking gallstone-related information, leaving 9210 individuals. Subsequently, we excluded 2851 participants with missing 2-day dietary data. After further excluding individuals under 20 years of age and those missing other relevant covariate data, the study encompassed 4628 subjects (Fig. 1).
Fig. 1.
Detailed flow chart of participant recruitment
Vitamin intake and determination of gallstones
NHANES diet-related data were collected using complex sampling methods. Dietary data for the first day were recorded by participants using a mobile examination cart (MEC), and the dietary data for the second day were obtained through telephone interviews conducted by the investigator. The intake of each vitamin in this study was averaged over these 2 days. Data on gallstones were collected from participants through a questionnaire asking, "Has a doctor ever told you that you have gallstones?" Participants who answered "yes" were classified as having gallstones.
Relevant covariates
To identify potential confounders, we selected several covariates for inclusion in a multifactorial regression model. These covariates encompassed basic demographic information, such as smoking status, BMI, education level, and race, as well as age, gender, diabetes and hyperlipidemia. Smoking status was determined by whether an individual had smoked at least 100 cigarettes in their lifetime. For diabetes, and hyperlipidemia, participant responses to the question, "Has a physician ever diagnosed you with the associated illness?" were used.
Statistical analysis
This research utilized RStudio and R version 4.3.3 for its analysis. Sample weights were applied in the calculations [28]. A p value below 0.05 was deemed to indicate statistical significance.
Initial traits were evaluated using the chi-square test for categorical variables and the t test for continuous variables. Logistic regression was employed for assessing the link of gallstone development and vitamin consumption. Three models were analyzed: Model 1 was unadjusted; Model 2 adjusted for demographic data, including race, age, and gender; and Model 3 included all covariates. We also conducted subgroup analyses and forest plots for vitamins statistically associated with gallstones and plotted restricted cubic spline (RCS) curves to model the risk associated with gallstone occurrence.
Results
Baseline data
This study included a total of 4,628 individuals, whose baseline data were categorized based on their characteristics. Participants were divided into two groups depending on whether they had gallstones. The data demonstrated a higher prevalence of gallstones among older adults, females, and individuals with obesity. Significant differences between the groups were also observed in terms of BMI, smoking habits, and the presence of hyperlipidemia. Regarding vitamin intake, disparities were noted in the daily consumption of vitamin E, vitamin B6, and niacin between the two groups (Table 1).
Table 1.
Baseline characteristics of participants with and without gallstone
| Characteristic | N1 | Overall N = 176,671,5772 |
Non-Gallstone N = 158,674,8562 |
Gallstone N = 17,996,7212 |
p value3 |
|---|---|---|---|---|---|
| Gender | 4628 | < 0.001 | |||
| Male | 2317 (51%) | 2174 (53%) | 143 (29%) | ||
| Female | 2311 (49%) | 1987 (47%) | 324 (71%) | ||
| Age | 4628 | 49 ± (17) | 48 ± (17) | 59 ± (15) | < 0.001 |
| Race | 4628 | 0.30 | |||
| Mexican American | 540 (8.3%) | 481 (8.4%) | 59 (7.5%) | ||
| Other Hispanic | 468 (7.3%) | 415 (7.3%) | 53 (7.0%) | ||
| Non-Hispanic White | 1767 (65%) | 1552 (64%) | 215 (70%) | ||
| Non-Hispanic Black | 1130 (9.8%) | 1050 (10%) | 80 (6.6%) | ||
| Other Race | 723 (9.7%) | 663 (9.8%) | 60 (9.1%) | ||
| Education | 4628 | 0.003 | |||
| Less than 9th grade | 253 (2.5%) | 237 (2.6%) | 16 (1.2%) | ||
| 9–11th grade | 475 (6.7%) | 426 (6.9%) | 49 (5.0%) | ||
| High school graduate | 1044 (26%) | 923 (25%) | 121 (36%) | ||
| Some college or AA degree | 1579 (31%) | 1407 (31%) | 172 (30%) | ||
| College graduate or above | 1277 (34%) | 1168 (35%) | 109 (27%) | ||
| Ratio of family income to poverty | 4628 | 3.26 ± (1.63) | 3.28 ± (1.63) | 3.00 ± (1.62) | 0.009 |
| BMI | 4628 | 28.8 ± (4.8) | 28.7 ± (4.7) | 30.1 ± (4.8) | 0.003 |
| Smoke | 4628 | 0.049 | |||
| Yes | 1938 (41%) | 1718 (41%) | 220 (48%) | ||
| No | 2690 (59%) | 2443 (59%) | 247 (52%) | ||
| Diabet | 4628 | 0.028 | |||
| Yes | 674 (11%) | 566 (10%) | 108 (18%) | ||
| No | 3821 (87%) | 3477 (88%) | 344 (78%) | ||
| Borderline | 133 (2.1%) | 118 (1.9%) | 15 (3.7%) | ||
| High blood pressure | 4628 | < 0.001 | |||
| Yes | 1744 (32%) | 1502 (31%) | 242 (48%) | ||
| No | 2884 (68%) | 2659 (69%) | 225 (52%) | ||
| High cholesterol | 4628 | < 0.001 | |||
| Yes | 1733 (36%) | 1499 (34%) | 234 (53%) | ||
| No | 2895 (64%) | 2662 (66%) | 233 (47%) | ||
| Total Cholesterol (mmol/L) | 4628 | 4.90 ± (1.07) | 4.89 ± (1.07) | 4.95 ± (1.12) | 0.60 |
| Triglycerides (mmol/L) | 4628 | 1.62 ± (1.22) | 1.62 ± (1.26) | 1.63 ± (0.85) | 0.033 |
| Vitamin E in diet (mcg) | 4628 | 9.2 ± (5.5) | 9.3 ± (5.6) | 8.0 ± (4.7) | < 0.001 |
| Vitamin E supplyment (mcg) | 4628 | 0.92 ± (3.04) | 0.96 ± (3.13) | 0.61 ± (2.02) | 0.12 |
| Vitamin E total (mcg) | 4628 | 10.1 ± (7.7) | 10.2 ± (7.8) | 8.7 ± (6.0) | 0.002 |
| Retinol (mcg) | 4628 | 402 ± (325) | 400 ± (312) | 420 ± (421) | 0.80 |
| Vitamin A (mcg) | 4628 | 618 ± (442) | 618 ± (438) | 614 ± (477) | 0.80 |
| Vitamin B1 (mcg) | 4628 | 1.56 ± (0.75) | 1.57 ± (0.75) | 1.48 ± (0.67) | 0.20 |
| Vitamin B2 (mcg) | 4628 | 2.08 ± (1.19) | 2.10 ± (1.23) | 1.88 ± (0.78) | 0.20 |
| Niacin (mcg) | 4628 | 26 ± (15) | 26 ± (15) | 21 ± (10) | < 0.001 |
| Vitamin B6 (mcg) | 4628 | 2.15 ± (1.83) | 2.20 ± (1.90) | 1.73 ± (0.85) | 0.001 |
| Vitamin B12 in diet (mcg) | 4628 | 4.67 ± (4.19) | 4.72 ± (4.20) | 4.18 ± (4.09) | 0.30 |
| Vitamin B12 supplyment (mcg) | 4628 | 1.01 ± (2.87) | 1.04 ± (2.99) | 0.73 ± (1.46) | > 0.90 |
| Vitamin B12 total (mcg) | 4628 | 5.7 ± (6.6) | 5.8 ± (6.8) | 4.9 ± (4.8) | 0.40 |
| Vitamin C (mcg) | 4628 | 75 ± (69) | 76 ± (69) | 72 ± (70) | 0.50 |
| Vitamin D (mcg) | 4628 | 4.3 ± (4.2) | 4.3 ± (4.3) | 3.9 ± (3.0) | 0.70 |
| Vitamin K (mcg) | 4628 | 126 ± (132) | 127 ± (133) | 116 ± (120) | 0.70 |
| Total Folate (mcg) | 4628 | 367 ± (187) | 371 ± (189) | 334 ± (162) | 0.023 |
| Folic Acid (mcg) | 4628 | 156 ± (142) | 156 ± (144) | 148 ± (121) | 0.40 |
| Food Folate (mcg) | 4628 | 212 ± (110) | 215 ± (112) | 186 ± (95) | 0.007 |
| Folate (mcg) | 4628 | 475 ± (273) | 480 ± (277) | 437 ± (236) | 0.040 |
| Lycopene (mcg) | 4628 | 4,689 ± (6,204) | 4,691 ± (6,244) | 4,672 ± (5,844) | 0.60 |
| Lutein and zeaxanthin (mcg) | 4628 | 1,616 ± (2,470) | 1,644 ± (2,495) | 1,369 ± (2,232) | 0.20 |
1N not Missing (unweighted)
2n (weighted) (%); Mean ± (SD)
3Pearson's X2: Rao and Scott adjustment; Design-based Kruskal–Wallis test
Correlation between vitamin intake and gallstone formation
In this study, we investigated the relationship between the intake of different types of vitamins and the risk of gallstone occurrence (Table 2). The results suggest that the intake of vitamin E, vitamin B6, and niacin may be potentially associated with a reduced risk of gallstones. In unadjusted models, the odds ratios (ORs) for gallstone risk were 0.96 (95% CI 0.94–0.99) for vitamin E, 0.73 (95% CI 0.61–0.88) for vitamin B6, and 0.96 (95% CI 0.95–0.98) for niacin. In tertile-based models, a trend of decreasing gallstone risk with increasing intake of these vitamins persisted. However, in the fully adjusted Model 3, only niacin retained a marginally significant association with gallstone risk (OR: 0.98, 95% CI 0.97–1.00). This suggests that the relationship between vitamin intake and gallstone risk may be influenced by multiple confounding factors (Table 3).
Table 2.
Association between vitamin categories and gallstone
| Model 1 OR(95%CI) p value |
Model 2 OR(95%CI) p value |
Model 3 OR(95%CI) p value |
|
|---|---|---|---|
| Vitamin E in diet (mcg) | 0.95(0.92,0.98) 0.005 | 0.97(0.93,1.00) 0.031 | 0.97(0.94,1.01) 0.11 |
| Vitamin E supplyment (mcg) | 0.95(0.89,1.02) 0.13 | 0.96(0.90,1.02) 0.14 | 0.97(0.94,1.01) 0.11 |
| Vitamin E total (mcg) | 0.96(0.94,0.99) 0.014 | 0.97 (0.95,1.00) 0.046 | 0.98(0.96,1.01) 0.13 |
| Retinol (mcg) | 1.00 (1.00,1.00) 0.30 | 1.00(1.00,1.00) 0.12 | 1.00(1.00,1.00) 0.20 |
| Vitamin A (mcg) | 1.00(1.00,1.00) 0.90 | 1.00(1.00,1.00) 0.70 | 1.00(1.00,1.00) > 0.90 |
| Vitamin B1 (mcg) | 0.84(0.68,1.03) 0.093 | 1.11(0.90,1.38) 0.30 | 1.12(0.89,1.40) 0.30 |
| Vitamin B2 (mcg) | 0.82(0.69,0.97) 0.023 | 0.94 (0.80,1.11) .0.50 | 0.93(0.76,1.13) 0.40 |
| Niacin | 0.96(0.95,0.98) < 0.001 | 0.99 (0,97,1.00) 0.043 | 0.98(0.97,1.00) 0.035 |
| Vitamin B6 (mcg) | 0.73(0.61,0.88) 0.002 | 0.86(0.74,1.01) 0.060 | 0.87(0.75,1.01) 0.064 |
| Vitamin B12 in diet (mcg) | 0.96(0.91,1.01) 0.12 | 1.00(0.96,1.04) > 0.90 | 1.00(0.95,1.04) 0.80 |
| Vitamin B12 supplyment (mcg) | 0.95(0.87,1.03) 0.20 | 0.99(0.92,1.08) 0.90 | 0.99(0.91,1.07) 0.70 |
| Vitamin B12 total (mcg) | 0.97(0.94,1.01) 0.13 | 1.00(0.97,1.03) > 0.90 | 1.00(0.96,1.03) 0.70 |
| Vitamin C (mcg) | 1.00(1.00,1.00) 0.50 | 1.00(1.00,1.00) 0.50 | 1.00(1.00,1.00) 0.90 |
| Vitamin D (mcg) | 0.97(0.93,1.01) 0.20 | 0.97(0.92,1.02) 0.20 | 0.97(0.91,1.03) 0.30 |
| Vitamin K (mcg) | 1.00 (1.00,1.00) 0.30 | 1.00 (1.00,1.00) 0.30 | 1.00(1.00,1.00) 0.70 |
| Folate (mcg) | 1.00(1.00,1.00) 0.079 | 1.00(1.00,1.00) > 0.90 | 1.00(1.00,1.00) 0.80 |
| Lycopene (mcg) | 1.00(1.00,1.00) > 0.90 | 1.00(1.00,1.00) 0.30 | 1.00(1.00,1.00) 0.20 |
| Lutein and zeaxanthin (mcg) | 1.00(1.00,1.00) 0.12 | 1.00(1.00,1.00) 0.20 | 1.00(1.00,1.00) 0.40 |
Model 1: no adjustment for covariates
Model 2: Covariates included age, gender, race
Model 3: Covariates included age, gender, race, education, BMI, whether they smoked, whether they were diabetic, hyperlipidemic
Table 3.
Association between Vitamin E, Vitamin B6, niacin and gallstone
| Model 1 OR(95%CI) p value |
Model 2 OR(95%CI) p value |
Model 3 OR(95%CI) p value |
|
|---|---|---|---|
| Vitamin E | 0.96(0.94,0.99) 0.014 | 0.97 (0.95,1.00) 0.046 | 0.98(0.96,1.01) 0.13 |
| Vitamin E.qtertile | |||
| Q1 (< 6.30) | Ref | Ref | Ref |
| Q2 (6.30 ~ 10.06) | 0.83(0.56,1.21) 0.30 | 0.89(0.60,1.32) 0.50 | 0.94(0.61,1.44) 0.70 |
| Q3 (> 10.06) | 0.56(0.40,0.79) 0.002 | 0.64(0.47,0.87) 0.007 | 0.70(0.49,1.00) 0.050 |
| p for trend | 0.00213 | 0.00722 | 0.050 |
| Model 1 OR(95%CI) p value |
Model 2 OR(95%CI) p value |
Model 3 OR(95%CI) p value |
|
|---|---|---|---|
| Vitamin B6 | 0.73(0.61,0.88) 0.002 | 0.86(0.74,1.01) 0.060 | 0.87(0.75,1.01) 0.064 |
| Vitamin B6.qtertile | |||
| Q1 (< 1.44) | Ref | Ref | Ref |
| Q2 (1.44 ~ 2.18) | 0.86(0.57,1.30) 0.50 | 0.95(0.62,1.46) 0.80 | 1.04(0.61,1.78) 0.90 |
| Q3 (> 2.18) | 0.49(0.30,0.78) 0.004 | 0.74(0.47,1.17) 0.20 | 0.77(0.45,1.30) 0.30 |
| p for trend | 0.0044 | 0.1815 | 0.2772 |
| Model 1 OR(95%CI) p value |
Model 2 OR(95%CI) p value |
Model 3 OR(95%CI) p value |
|
|---|---|---|---|
| Niacin | 0.96(0.95,0.98) < 0.001 | 0.99 (0,97,1.00) 0.043 | 0.98(0.97,1.00) 0.035 |
| Niacin.qtertile | |||
| Q1 (< 18.81) | Ref | Ref | Ref |
| Q2 (18.81 ~ 27.61) | 0.63(0.48,0.82) 0.001 | 0.75(0.58,0.97) 0.029 | 0.75(0.57,0.98) 0.037 |
| Q3 (> 27.61) | 0.35(0.22,0.58) < 0.001 | 0.64(0.40,1.03) 0.066 | 0.61(0.37,1.02) 0.056 |
| p for trend | 0.000229 | 0.0660 | 0.05610 |
Model 1: not adjustment for covariates
Model 2: Covariates included age, gender, race
Model 3: Covariates included age, gender, race, education, BMI, whether they smoked, whether they were diabetic, hyperlipidemic
Stratification study
To evaluate the robustness of the association between the intake of vitamin E, vitamins B6 and niacin and gallstone occurrence, subgroup analyses were conducted and forest plots for Model 3 were generated (Fig. 2). The results indicated that the intake levels of these three vitamins did not significantly vary among subgroups in terms of gallstone risk.
Fig. 2.
Subgroup analyses for the association between vitamin intake and gallstone risk. Models were adjusted for gender, age, race, education, BMI, smoking, presence of diabetes and hyperlipidemia. A Vitamin E with gallstone risk, B Vitamin B6 with gallstone risk, C Niacin with gallstone risk. BMI, body mass index; DM, diabetes mellitus; OR, odds ratio
RCS curves
To further determine potential linear relationships between vitamin intake and gallstone risk, restricted cubic spline (RCS) curves were plotted. Curve fitting was performed separately for each vitamin, adjusted for model 3 (Fig. 3). The analysis revealed a potential linear association between niacin intake with gallstone risk, demonstrating a consistent decrease in gallstone risk as the intake of this vitamin increased.
Fig. 3.
RCS curve of the association between vitamin intake and gallstone risk. A, D RCS curve of Vitamin E and gallstones, B, E RCS curve of Vitamin B6 and gallstones, C, F RCS curve of Niacin and gallstones. RCS, restricted cubic spline; BMI, body mass index; DM, diabetes mellitus; OR, odds ratio
Discussion
Gallstones are a widespread and significant health issue globally. With improvements in living standards and increased public health awareness, the use of vitamin supplements has grown. However, the existing research on the effects of vitamin intake on gallstones remains somewhat limited. This study utilized the NHANES database to examine the correlation between vitamin intake and gallstones. Our findings affirm that gallstones are more prevalent in women and older adults, consistent with previous research [16]. We observed notable differences in niacin, vitamin B6, and vitamin E intake between individuals with and without gallstones. Our logistic regression analysis revealed that an increased intake of niacin, vitamin E and vitamin B6 might show associations with a decreased incidence of gallstones. In addition, the RCS curves we plotted suggested a potential linear relationship between niacin and the risk of developing gallstones.
The literature lacks extensive cohort studies or experimental research on the relationship between various vitamin intakes and gallstone formation. Some previous studies have suggested that vitamin C may influence the development of gallstones. For example, a study by Simon et al. in [17] showed that in women, as the serum ascorbic acid levels increased, the risk of developing gallstones decreased, but this phenomenon was not observed in men. Thomas Walcher et al. in [18], analyzed data from 2129 individuals in Southern Germany and observed that vitamin C supplementation showed associations with a reduced incidence of gallstones. This may be because vitamin C deficiency impairs cholesterol 7α-hydroxylation, leading to a decrease in bile acid biosynthesis and causing cholesterol supersaturation in the bile [9]. In addition, Sabina Waniek et al. reported that circulating levels of vitamin E were inversely associated with gallstone prevalence [19], while the study by Helen V. Worthington et al. confirmed that a dietary deficiency in vitamin E could disrupt glutathione homeostasis, thereby increasing gallstone risk [20]. Niacin, also known as vitamin B3, is primarily derived from meat, fish, and legumes. In the body, it is converted to NAD + and NADP + , which are crucial for metabolism, redox reactions, and other biological processes [21]. Niacin is used clinically to increase HDL cholesterol and decrease LDL cholesterol levels [22]. However, recent studies have shown that in combination with statin therapy, niacin therapy may increase mortality among patients with cardiovascular diseases and shows associations with the onset of cardiovascular disorders and inflammation in blood vessels through the metabolic end products of niacin [23]. A previous study by R. E. Holland et al. demonstrated that niacin increases bile flow rate and reduces blood lipids in rats by enhancing bile secretion [24]. Vitamin B6, found in many foods, serves as a key coenzyme for numerous biological processes, with pyridoxine, pyridoxal, and pyridoxamine as its three natural forms [25]. Deficiencies in Vitamin B6 have shown associations with a variety of diseases, including diabetes, inflammation, tumors, and cardiovascular disease [26]. Prior research has indicated that Vitamin B6 may reduce the incidence of kidney stones by decreasing oxalate levels [27]. However, the link of the consumption of these vitamins and gallstone occurrence has not been conclusively demonstrated through systematic studies. Our analysis of the NHANES database revealed that higher niacin, vitamin E and Vitamin B6 consumption levels show associations with a decreased risk of gallstones.
This study utilizes the NHANES database to conduct a large-sample cross-sectional study, exploring the association between vitamin intake and the risk of gallstone occurrence. We found that the association between Vitamin C and gallstones may not be as definitive as expected across a wide sample population, indicating that further research in this area is necessary. In addition, this study identified three vitamins—niacin, Vitamin E and Vitamin B6—that are potentially associated with a reduced risk of gallstones, providing new research directions for future studies and potential implications for gallstone prevention and treatment strategies.
However, this study has several limitations. First, as this is a cross-sectional study, it is not possible to establish a causal relationship between vitamin intake and the occurrence of gallstones. Second, the NHANES database surveys a U.S. population, which may introduce population heterogeneity. Third, although the study adjusted for multiple covariates, such as age, gender, BMI, and smoking, there may still be unmeasured confounding factors that could affect the results. Fourth, this study on the diagnosis of gallstones is based on self-reported survey questionnaires, lacking imaging-related evidence. Fifth, since this is a cross-sectional study, we can only use the dietary information provided by the NHANES database to infer participants' long-term vitamin intake. However, due to the lack of information on the duration of vitamin intake, this may have some impact on the results. While this study provides statistical insights, further validation through cohort studies or experimental research is necessary.
Conclusion
In the U.S. population, higher niacin intake showed a marginal inverse association with gallstones after full adjustment, while vitamins B6 and E exhibited protective trends only in unadjusted models. Future longitudinal and mechanistic studies should clarify the role of vitamins in gallstone formation. Public health emphasis on balanced diets over supplements remains prudent.
Abbreviations
- US
United States
- NHANES
National Health and Nutrition Examination Survey
- NCHS
National Center for Health Statistics
- DM
Diabetes Mellitus
- BMI
Body Mass Index
- OR
Odds Ratio
- CI
Confidence Interval
- RCS
Restricted Cubic Spline
Author contributions
P.C. CHEN and Q.F. Zhang design the project, P.C.CHEN and C.F.L.Yang analyses the data, P.C. CHEN, C.F.L. Yang, Y. Li, J.R. Ding, W. Hu co-write the article.
Funding
This research did not receive any specific grant from funding agencies in public, commercial, or not-for profit sectors.
Data availability
Data described in the manuscript will be made publicly and freely available without restriction at NHANES. https://www.cdc.gov/nchs/nhanes/
Declarations
Ethics approval and consent to participate
The research was carried out in compliance with the ethical principles outlined in the Declaration of Helsinki. All study procedures involving human participants were reviewed and approved by the Institutional Review Board of the National Center for Health Statistics (NCHS). In addition, written informed consent was secured from each participant/patient involved in the study.
Consent for publication
Not applicable.
Competing Of interestS
The authors declare that they have no conflict of interest.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Pinchu Chen and Chenfenglin Yang contributed equally to this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data described in the manuscript will be made publicly and freely available without restriction at NHANES. https://www.cdc.gov/nchs/nhanes/