PLOS ONE

RESEARCH ARTICLE

Association between plant-based dietary

index and gallstone disease: A cross sectional
study from NHANES
Luyang Li ID1, Chengli Liu ID1,2,3*, Tian Xia3, Haoming Li1, Jun Yang1, Meng Pu2,
Shuhan Zhang2, Yingbo Ma2, Tao Zhang2
1 Postgraduate Training Base of Air Force Medical Center, China Medical University, Beijing, China,
2 Department of Hepatobiliary Surgery, Air Force Medical Center, Air Force Medical University, Beijing,
China, 3 Graduate School of Hebei North University, Zhangjiakou, Hebei, China
a1111111111
a1111111111 * liuchengli_beijing@163.com
a1111111111
a1111111111
a1111111111 Abstract
Background
The relationship between plant-based diets and gallstone disease has been debated. This
OPEN ACCESS study aimed to shed light on the association between plant-based dietary index and the risk
Citation: Li L, Liu C, Xia T, Li H, Yang J, Pu M, et al. of developing gallstone disease.
(2024) Association between plant-based dietary
index and gallstone disease: A cross sectional
study from NHANES. PLoS ONE 19(6): e0305822. Methods
https://doi.org/10.1371/journal.pone.0305822 Eligible participants were selected from National Health and Nutrition Examination Survey
Editor: Wen-Wei Sung, Chung Shan Medical (NHANES) 2017–2020. Three plant-based diet indexes (PDI, healthy PDI, unhealthy PDI)
University, TAIWAN were calculated using data from two NHANES 24-h dietary recall interviews. Restricted
Received: March 9, 2024 Cubic Spline and multivariate logistic regression were used to analyze the associations.
Accepted: June 4, 2024 Subgroup analysis was adopted to make the results more robust.

Published: June 25, 2024

Results
Copyright: © 2024 Li et al. This is an open access
article distributed under the terms of the Creative A total of 5673 eligible participants were analyzed. After adjusting for various confounding
Commons Attribution License, which permits variables, uPDI was positively associated with gallstone disease (OR = 1.53, 95%CI: 1.02–
unrestricted use, distribution, and reproduction in 2.29). No association was found between PDI/hPDI and gallstone disease (p > 0.05). The
any medium, provided the original author and
results of subgroup analysis did not show any positive association between uPDI and gall-
source are credited.
stones in specific groups.
Data Availability Statement: All relevant data are
within the manuscript and its Supporting
information files. Conclusion
Funding: Clinical research project of Air Force Our study shows that the elevated uPDI are linked to a higher risk of gallstone disease.
Medical Center, PLA, Air Force Medical University,
grant number 2021LC013. The funders had no role
in study design, data collection and analysis,
decision to publish, or preparation of the
manuscript. Introduction
Competing interests: The authors have declared Gallstone disease (GD) is one of the most common gastrointestinal disorders [1]. The preva-
that no competing interests exist. lence and incidence of GD varies between countries and ethnicities. About 10% to 15% of

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 1 / 11

PLOS ONE Plant-based dietary index and gallstone disease

Americans suffer from GD [2]. Gallstones are classified into three types: cholesterol stones, pig-
ment stones, and mixed stones. In the western world, cholesterol stones are the most common
[3]. The increased secretion of cholesterol in bile, crystallization, and reduced gallbladder con-
tractility are linked to the development of cholesterol gallstones. The main cause of pigment
gallstones is biliary tract infection. GD is usually asymptomatic. Comorbidities such as pancre-
atitis, cholangitis, and cholecystitis are major sources of surgical procedures and hospital
admissions. These conditions place a significant financial strain on healthcare resources. It is
important to address these comorbidities to reduce the burden on the healthcare system [2,4].
5Fs (forty years of age, female, fatty, fair, and fertile) are considered traditional risk factors
for gallstones [5]. Multiple foods and nutrients are also associated with the risk of GD, and this
association is complex. Previous research has shown that the risk of GD is negatively correlated
with the consumption of vegetables and fiber, and positively correlated with high caloric, fat,
and saturated fatty acid intake from meat [6]. Some research shown that vegetarian diet is a
protective factor for gallstone disease [7]. However, some studies have concluded that vegetar-
ian diets increase the risk of gallstone disease [8]. The inconsistent conclusions of these studies
may be attributed to differences in the quality of plant-based diet and lack of quantitative eval-
uation of plant-base diet.
Plant-based dietary indexes are frequently suggested as healthy dietary alternatives due to
their higher intake of plant foods and lower consumption of animal foods [9,10]. Compared
with previous researches that treated plant foods equally, the Plant-based Dietary Index (PDI)
further segregates plant-based diets into hPDI and uPDI categories. Studies showed that PDI
can result in a lower risk of all-cause mortality and improved health conditions for individuals
with disease such as hypertension, cardiovascular disease and diabetes [11,12].
In this study, we examined the association between plant-based diet, its quality and the risk
of gallstone disease.

Materials and methods

Study design and population
A sophisticated, multistage, random sampling design is employed in the National Health and
Nutrition Examination Survey (NHANES), a nationally representative study. NHANES data
has been approved by the NCHS Ethics Review Board (ERB), and informed consent was
obtained in writing from all participants in this national survey. In this study, we extracted
data from NHANES between 2017 and 2020. In a survey conducted by trained professional
interviewers, respondents were asked the question: "Has a doctor or other health professional
ever diagnosed you with gallstones? " The results of the survey showed that individuals who
answered "yes" were considered to have gallstones, while those who answered "no" were con-
sidered to be free of gallstone disease. Exclusion criteria were as follows: (1) participants
aged < 20years old; (2) participants with incomplete gallstone data; (3) participants with
incomplete two 24-h dietary recall interviews data; (4) participants with incomplete covariates.
(Fig 1) shows a thorough illustration of the inclusion and exclusion procedure.

Plant-based dietary index

PDI, hPDI, uPDI were calculated using methods similar to previous studies [11,13]. The aver-
age of two 24-hour recall NHANES interviews were used to gather dietary intake data, which
were then taken from the food-pattern-equivalency database after being converted to the
appropriate food equivalents. Table 1 shows the food grouping and scoring rules. Food groups
were ranked into quintiles by consumption and those with highest consumption received a 5
while those with the lowest or no consumption received a 0. Likewise, reverse score is that

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 2 / 11

PLOS ONE Plant-based dietary index and gallstone disease

Fig 1. Flow chart illustrating selection of the study population in NHANES from 2017 to 2020.
https://doi.org/10.1371/journal.pone.0305822.g001

food groups with highest consumption received a 0 and those with the lowest or no consump-
tion received a 5. Each subject’s scores were summed to obtain a score for each index, with a
theoretical range of 15 to 75. Finally, these index variables were treated as continuous and cate-
gorical (in quintiles), respectively.

Definition of covariates
Participants’ demographic characteristics (age, gender, ethnicity, body mass index (BMI), and
waistline), lifestyle (smoking status and sitting time), and history of disease (diabetes and

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 3 / 11

PLOS ONE Plant-based dietary index and gallstone disease

Table 1. Calculation of three PDIs.

Food groups PDI hPDI uPDI
Healthy plant foods
Whole grains + + -
Fruits + + -
Vegetables + + -
Nuts + + -
Legumes + + -
Less healthy food
Fruit juices + - +
Refined grains + - +
Potatoes + - +
Sugar + - +
Animal food group
Dairy - - -
Egg - - -
Fish or seafood - - -
Meat - - -

Abbreviations: PDI, plant-based diet index; hPDI, healthy plant-based diet index; uPDI, unhealthy plant-based diet
index.

https://doi.org/10.1371/journal.pone.0305822.t001

hypertension) were considered as covariates in the present study. Smoking status was defined
by serum continine levels, which included: (i) non-smoker (<1.0 ng/mL); (ii) environmental
tobacco smoke (ETS) exposure (1.0–9.9 ng/mL); (iii) current smoker (�10 ng/mL).

Statistical analysis
The NCHS-recommended sampling weights were employed in all analyses to take into consid-
eration the intricate NHANES survey design. This study incorporated interview weight vari-
ables (WTINT2YRs) in all of this analyses to guarantee nationally representative estimates. To
account for standard errors (SEs) associated with complex survey designs, this study utilized
the primary sampling unit variable (SDMVPSU) and the stratification variable (SDMVSTRA).
Continuous variables were reported as medians and interquartile ranges (25th and 75th per-
centiles), analysis was performed with ANOVA. Categorical variables were presented as abso-
lute variables and frequencies, analysis was performed with the Chi-square test. Restricted
cubic splines were used to flexibly model the association between PDI and the risk of gallstone
disease. Survey-weighted multivariable logistic regression models were used to investigate the
relationship between PDI and the risk of gallstones. A difference was considered statistically
significant if it was p < 0.05, and all statistical tests were two-tailed. All analyses were per-
formed using R software (4.1.0, R core team).

Results
Participant characteristics
A total of 5673 participants were included in this study. The mean age of participants was 48
years old. Among them, there were 48.76% male and 51.24% female. The differences in age,
gender, race, waist, BMI, diabetes and hypertension between the non-gallstones and gallstone
group were significant (p < 0.05). Participants in the gallstone group have a larger waist

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 4 / 11

PLOS ONE Plant-based dietary index and gallstone disease

circumference, a higher BMI, and a higher incidence of hypertension. The majority of them
were women. Table 2 presents the detailed participant characteristics. The mean scores of PDI,
hPDI and uPDI were 39.8 ± 5.1, 40.8 ± 6.1, and 38.9 ± 5.4, respectively. Participants over 80
years old, Mexican American, those with BMI between 25 and 29.9 Kg/m2, those without dia-
betes, those without hypertension, and non-smoker had higher PDI. Female had higher hPDI
compared with male. Participants between 20 and 40 years old, Non-Hispanic Black, those
with BMI below 18.5 Kg/m2, those without diabetes had higher uPDI. The detailed scores were
shown in Table 3.

Correlation between PDI, hPDI, uPDI and gallstones

As is shown in (Fig 2), we used restricted cubic splines to visualize the relation of PDI, hPDI,
uPDI with the odds of GD after adjusting all factors (p > 0.05).
Multivariate logistic regression results for the association of three PDI and GD were illus-
trated in Table 4. In the model 1, we adjusted age, gender and race. Then we further adjusted
demographic characteristics and history of disease in the model 2. Finally, we adjusted all
covariates in the model 3. Significant reverse associations were observed between odds of GD
and hPDI in model 1 (ORQ4vsQ1 = 0.66, CI = 0.44–0.99). In all three models, there is a positive
association between uPDI and GD(Model 1: ORQ4vsQ1 = 1.71, CI = 1.23–2.39; Model 2:
ORQ4vsQ1 = 1.57, CI = 1.08–2.29; Model 3: ORQ4vsQ1 = 1.53, CI = 1.02–2.29;p for trend <0.05).
Then we further explore the association between uPDI and GD in different subgroups.
Table 5 presents the logistic regression results and reports of a linear trend test (P for trend) in
different age, gender, race, BMI, smoking status subgroup. There is no significant interaction
between uPDI and other variables.

Disscussion
Diet has always been considered a crucial factor in the formation of gallstones and the onset of
gallstone related diseases. This study investigated the association of an association between
three plant-based diet indexes and GD. We identified higher score of uPDI was independently
associated with gallstones based on large-scale epidemiological data from NHANES. There is
not such an association between PDI/hPDI and GD.
There have been several researches about the association between vegetarian diet and risk
of gallstones, which are controversial between each other [7,8,14]. Research from Europe con-
cluded that significant positive association between vegetarian diet and symptomatic gallstone
disease [8]. But a cohort study from Taiwan reported that a vegetarian diet is associated with a
lower incidence of symptomatic GSD in women [7]. These differences may be attributed to
different population choices. The former consumes more starch. Due to the vegetarian partici-
pants were almost Buddhists, the latter consume a healthy diet (adequate amount of fiber and
vegetables). Our research calculated three plant-based diet indexes which further subdivided
plant-based diet into healthy and unhealthy categories while considering meat intake. So, the
conclusion is more applicable to the general population. Many researches also investigated the
relationship between single dietary components and gallstones [15–17]. For example, one
research concluded that low fiber intake might increase the risk of cholesterol gallstones [18].
Starch consumption was positively associated with gallstones risk [7]. In our research, in the
calculation of unhealthy PDI, a high score mainly represents a lower intake of meat, a lower
intake of healthy food, and a higher intake of unhealthy plant-based food. Our research not
only consistent with the previous research findings, but also takes into account the interactions
between foods, which is more robust. Additionally, there is limited data on the correlation
between overall dietary habits and the risk of GD illness. A cohort study conducted among

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 5 / 11

PLOS ONE Plant-based dietary index and gallstone disease

Table 2. Baseline characteristics of eligible participants.

Characteristic Overall (N = 5,673) Non-Gallstones (N = 5,075) Gallstones (N = 598) p-Value
Age (years) 48 (33, 62) 47 (32, 61) 59 (46, 70) <0.001
Gender <0.001
Male 2,759 (48.76%) 2,585 (51.27%) 174 (27.68%)
Female 2,914 (51.24%) 2,490 (48.73%) 424 (72.32%)
Race/ethnicity 0.045
Mexican American 635 (8.00%) 565 (8.08%) 70 (7.26%)
Non-Hispanic Black 1,528 (10.86%) 1,407 (11.27%) 121 (7.50%)
Non-Hispanic White 2,104 (63.65%) 1,825 (62.84%) 279 (70.44%)
Other 1,406 (17.49%) 1,278 (17.81%) 128 (14.80%)
Waist (cm) 99.80 (89.40, 111.00) 99.20 (88.50, 110.00) 106.40 (95.55, 119.51) <0.001
BMI (Kg/m2) <0.001
< 18.5 68 (1.00%) 67 (1.11%) 1 (0.03%)
18.5–24.9 1,316 (24.50%) 1,250 (25.86%) 66 (13.18%)
25–29.9 1,755 (31.81%) 1,600 (32.11%) 155 (29.27%)
� 30 2,534 (42.69%) 2,158 (40.92%) 376 (57.51%)
Diabetes <0.001
No 4,594 (85.82%) 4,184 (87.03%) 410 (75.65%)
Yes 1,079 (14.18%) 891 (12.97%) 188 (24.35%)
Hypertension <0.001
No 3,054 (60.60%) 2,830 (62.92%) 224 (41.22%)
Yes 2,619 (39.40%) 2,245 (37.08%) 374 (58.78%)
Smoking status 0.400
Non-smoker 4,086 (74.25%) 3,630 (74.03%) 456 (76.06%)
ETS 208 (3.08%) 189 (3.22%) 19 (1.91%)
Current smoker 1,379 (22.67%) 1,256 (22.75%) 123 (22.02%)
Sitting time 300 (180.00, 480.00) 300 (180.00, 480.00) 360 (240.00, 480.00) 0.300
PDI 0.500
Q1 1,160 (20.18%) 1,036 (20.37%) 124 (18.54%)
Q2 1,592 (27.43%) 1,412 (27.04%) 180 (30.68%)
Q3 1,224 (21.60%) 1,114 (21.93%) 110 (18.82%)
Q4 1,697 (30.80%) 1,513 (30.66%) 184 (31.96%)
hPDI >0.900
Q1 1,406 (22.37%) 1,265 (22.53%) 141 (21.02%)
Q2 1,367 (23.73%) 1,224 (23.70%) 143 (24.02%)
Q3 1,321 (23.62%) 1,183 (23.70%) 138 (22.99%)
Q4 1,579 (30.27%) 1,403.00 (30.07%) 176.00 (31.97%)
uPDI 0.300
Q1 1,194 (24.58%) 1,074 (25.08%) 120 (20.43%)
Q2 1,447 (27.90%) 1,297 (28.00%) 150 (26.99%)
Q3 1,553 (24.89%) 1,383 (24.50%) 170 (28.12%)
Q4 1,479 (22.63%) 1,321 (22.41%) 158 (24.45%)

Abbreviations: BMI, body mass index; ETS, environmental tobacco smoke; PDI, plant-based diet index; hPDI, healthy plant-based diet index; uPDI, unhealthy plant-
based diet index.

https://doi.org/10.1371/journal.pone.0305822.t002

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 6 / 11

PLOS ONE Plant-based dietary index and gallstone disease

Table 3. The scores of dietary patterns in different subgroups.

Variables PDI hPDI uPDI
Total participants 39.8 ± 5.1 40.8 ± 6.1 38.9 ± 5.4
Gallstones group
Non-gallstones 39.8 ± 5.2 40.8 ± 6.2 38.9 ± 5.5
Gallstones 39.7 ± 5.0 41.1 ± 5.9 39.1 ± 5.3
Age (years)
20–40 39.5 ± 5.2 39.8 ± 6.1 39.7 ± 5.6
41–60 40.0 ± 5.1 40.8 ± 6.3 38.8 ± 5.5
61–80 39.8 ± 5.2 41.7 ± 5.9 38.2 ± 5.2
>80 40.3 ± 4.8 41.7 ± 5.6 38.7 ± 4.9
Gender
Male 39.8 ± 5.2 39.7 ± 6.1 38.9 ± 5.4
Female 39.8 ± 5.1 41.9 ± 6.0 38.9 ± 5.4
Race/ethnicity
Mexican American 40.7 ± 5.2 41.1 ± 5.8 38.1 ± 5.3
Non-Hispanic Black 39.2 ± 4.9 39.2 ± 6.1 40.5 ± 5.2
Non-Hispanic White 39.8 ± 5.1 41.1 ± 5.9 38.5 ± 5.4
Other 40.0 ± 5.4 41.9 ± 6.3 38.0 ± 5.5
BMI (Kg/m2)
< 18.5 39.7 ± 5.2 39.4 ± 6.5 40.5 ± 6.0
18.5–24.9 40.1 ± 5.3 41.1 ± 6.4 38.7 ± 5.7
25–29.9 40.3 ± 5.3 41.5 ± 6.2 38.5 ± 5.4
� 30 39.3 ± 4.9 40.2 ± 5.9 39.2 ± 5.3
Diabetes
No 39.9 ± 5.2 40.7 ± 6.2 39.0 ± 5.5
Yes 39.4 ± 5.1 41.4 ± 5.9 38.4 ± 5.2
Hypertension
No 40.0 ± 5.3 40.8 ± 6.2 38.8 ± 5.6
Yes 39.6 ± 5.0 40.8 ± 6.1 39.0 ± 5.2
Smoking status
Non-smoker 40.2 ± 5.2 41.5 ± 6.1 38.2 ± 5.4
ETS 39.0 ± 5.3 38.9 ± 6.0 40.7 ± 5.2
Current smoker 38.7 ± 4.8 39.1 ± 5.9 40.6 ± 5.1

Note: A statistically significant difference was defined as p < 0.05 and data with p values below 0.05 are presented in bold type. Abbreviations: BMI, body mass index;
ETS, environmental tobacco smoke; PDI, plant-based diet index; hPDI, healthy plant-based diet index; uPDI, unhealthy plant-based diet index.

https://doi.org/10.1371/journal.pone.0305822.t003

French medical professionals found that increased adherence to MED was associated with a
decreased incidence of GD disease symptoms [19]. However, non-Mediterranean countries
often lack high-quality sources of MUFA due to the infrequent use of olive oil. Dena PER-
SIAN’s research suggests that a proinflammatory diet is linked to a lower risk of GSD [20]. In
contrast to these dietary regimens, PDI is considered to be more practical.
The exact mechanisms of gallstone formation are still unclear. The mechanisms involved in
this process include increased hepatic cholesterol synthesis, elevated insulin levels, and hyper-
secretion of cholesterol into bile, resulting in increased biliary cholesterol saturation. A large
intake of refined grains leads to a negative effect on colonic motility, and increased production
of secondary bile acids. These may all be related to the increased risk of gallstone disease
caused by uPDI. In addition, many diets in uPDI also belong to pro-inflammatory diets.

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 7 / 11

PLOS ONE Plant-based dietary index and gallstone disease

Fig 2. Dose-response association of three plant-based dietary index and gallstone disease. (A) the association of PDI and GD; (B) the association of hPDI
and GD; (C) the association of uPDI and GD. Hazard ratios from restricted cubic splines were adjusted for age, gender, race/ethnicity, waist, BMI, diabetes,
hypertension, smoking status and sitting time. Models accounted for National Health and Nutrition Examination Survey complex design and weights.
https://doi.org/10.1371/journal.pone.0305822.g002

Gallstone development can be caused by inflammation-induced changes in the metabolism of

proteins and lipids, which can also impact the metabolism of cholesterol and bile acids, as well
as increase bile salt levels [21].
To reduce the risk of gallstone disease, participants may consider reducing their intake of
unhealthy plant-based foods, as well as lowering their risk of diabetes, obesity, and cardiovas-
cular disease [9,10,22]. Moreover, an increasing amount of research highlights the environ-
mental benefits of transitioning to more sustainable plant-based diets. The global adoption of
plant-based diets could result in significant reductions in greenhouse gas emissions, land clear-
ance, and freshwater consumption, particularly in high-income countries where animal pro-
tein consumption is high. Switching to a mostly plant-based diet may have significant benefits
for both environmental and human health [23,24].

Table 4. Odds ratio (95%CI) for gallstones by quartiles of dietary patterns and as a continuous variable among eligible participants.
Dietary patterns Q1 Q2 Q3 Q4 As continuous variables P for Trend p-Value
PDI
Model 1 1.00 1.29 (0.83,2.00) 1.00 (0.58,1.74) 1.14 (0.96,1.87) 1.00 (0.96,1.04) 0.868 >0.900
Model 2 1.00 1.25 (0.80,1.94) 1.08 (0.59,1.98) 1.24 (0.75,2.06) 1.01 (0.97,1.05) 0.497 0.600
Model 3 1.00 1.28 (0.79,2.08) 1.12 (0.58,2.15) 1.32 (0.74,2.34) 1.01 (0.97,1.05) 0.385 0.500
hPDI
Model 1 1.00 0.78 (0.55,1.10) 0.69 (0.41,1.15) 0.66 (0.44,0.99) 0.98 (0.95,1.00) 0.065 0.087
Model 2 1.00 0.83 (0.56,1.24) 0.76 (0.43,1.35) 0.86 (0.54,1.38) 0.99 (0.96,1.02) 0.485 0.600
Model 3 1.00 0.84 (0.55,1.28) 0.77 (0.41,1.42) 0.87 (0.52,1.45) 0.99 (0.96,1.03) 0.517 0.700
uPDI
Model 1 1.00 1.21 (0.81,1.82) 1.52 (1.02,2.28) 1.71 (1.23,2.39) 1.04 (1.01,1.07) 0.004 0.005
Model 2 1.00 1.20 (0.74,1.96) 1.38 (0.91,2.11) 1.57 (1.08,2.29) 1.03 (1.01,1.06) 0.025 0.024
Model 3 1.00 1.19 (0.71,1.98) 1.35 (0.87,2.10) 1.53 (1.02,2.29) 1.03 (1.00,1.06) 0.048 0.044

Note: Values are odds ratios (95%CI) from logistic regression. Model 1: adjusted for age, gender, race/ethnicity; Model 2: Model 1 plus waist, BMI, diabetes, and
hypertension; Model 3: Model2 plus smoking status, and sitting time; a statistically significant difference was defined as p < 0.05 and data with p values below 0.05 are
presented in bold type. Abbreviations: OR, odds ratio; 95% CI, 95% confidence interval; PDI, plant-based diet index; hPDI, healthy plant-based diet index; uPDI,
unhealthy plant-based diet index.

https://doi.org/10.1371/journal.pone.0305822.t004

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 8 / 11

PLOS ONE Plant-based dietary index and gallstone disease

Table 5. Subgroup analyses of the association between quartiles of uPDI and gallstones.
uPDI p for Trend p for Interaction
Q1 Q2 Q3 Q4
Age (years) 0.828
20–40 1.00 1.86 (0.35,9.80) 1.94 (0.54,6.98) 2.18 (0.60,7.87) 0.200
41–60 1.00 1.06 (0.42,2.64) 1.21 (0.64,2.29) 1.05 (0.58,1.92) 0.700
61–80 1.00 1.06 (0.59,1.91) 1.28(0.65,2.53) 1.70(0.77,3.74) 0.140
>80 1.00 2.45 (0.71,8.46) 1.08(0.32,3.64) 1.27(0.31,5.20) >0.900
Gender 0.794
Male 1.00 1.01 (0.42,2.44) 1.59(0.55,4.58) 1.73(0.67,4.50) 0.140
Female 1.00 1.28 (0.67,2.43) 1.24(0.78,1.97) 1.41(0.97,2.05) 0.120
Race/ethnicity 0.132
Mexican American 1.00 0.65 (0.10,4.08) 2.05(0.39,10.9) 0.90(0.12,6.77) 0.600
Non-Hispanic Black 1.00 1.25 (0.52,3.01) 1.85(0.76,4.48) 0.99(0.36,2.69) 0.800
Non-Hispanic White 1.00 1.32 (0.71,2.44) 1.18 (0.69,2.00) 1.59(0.94,2.69) 0.130
Other 1.00 0.93 (0.45,1.95) 1.62 (0.76,3.45) 2.25(0.93,5.45) 0.043
BMI (Kg/m2) 0.112
18.5–24.9 1.00 2.10 (0.55,7.98) 1.41 (0.54,3.66) 0.79 (0.23,2.70) 0.500
25–29.9 1.00 1.51 (0.67,3.38) 1.11 (0.37,3.31) 1.95 (0.88,4.35) 0.200
� 30 1.00 0.77 (0.41,1.45) 1.33 (0.81,2.17) 1.40 (0.82,2.38) 0.063
Smoking status 0.394
Non-smoker 1.00 1.11 (0.71,1.76) 1.35 (0.83,2.18) 1.64 (0.99,2.70) 0.048
ETS 1.00 4.32(0.15,127.00) 4.87 (0.19,125) 22.5 (1.50,337) 0.031
Current smoker 1.00 1.85 (0.63,5.44) 1.29 (0.51,3.22) 0.96 (0.41,2.22) 0.700

Multivariable logistic regression models were adjusted for age, gender, race/ethnicity, waist, BMI, diabetes, hypertension, smoking status and sitting time. Stratification
variables were not adjusted in the corresponding models. Abbreviations: uPDI, unhealthy plant-based diet index; BMI, body mass index; ETS, environmental tobacco
smoke.

https://doi.org/10.1371/journal.pone.0305822.t005

Our study’s advantages include the use of a large, representative sample of national data,
ensuring reliable results. In our study, we took restricted cubic spline to exclude the non-linear
relationship between uPDI and gallstone disease. However, several limitations should be con-
sidered. First, the NHANES cross-sectional design suggests that causal links cannot be estab-
lished. Secondly, the use of 24-h dietary recall may not fully reflect habitual dietary intake of
the participants since it is unable to account day-to-day variation and participants may change
their diet during the follow-up periods. Thirdly, although we adjusted for multiple covariates,
we were unable to control for some untested confounders and residual covariates, which could
lead to confounding bias. The outcome compensated for previous studies, but further large-
scale prospective cohorts are still needed for validation. Further interventional studies and
experimental research are warranted to identify the impact of high quality plant-based diets on
asymptomatic patients who with gallstones and patients who have undergone
cholecystectomy.

Conclusion
Our study shows that the elevated uPDI are linked to a higher risk of gallstone disease. There is
no significant relationship between PDI/uPDI and gallstone diseases.

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 9 / 11

PLOS ONE Plant-based dietary index and gallstone disease

Supporting information
S1 Table. Original data.
(CSV)

Author Contributions
Conceptualization: Chengli Liu.
Data curation: Haoming Li, Yingbo Ma.
Formal analysis: Luyang Li, Tian Xia, Jun Yang, Meng Pu, Shuhan Zhang, Yingbo Ma, Tao
Zhang.
Methodology: Jun Yang, Shuhan Zhang, Tao Zhang.
Supervision: Chengli Liu.
Writing – original draft: Luyang Li, Meng Pu.
Writing – review & editing: Tian Xia, Haoming Li.

References
1. Marschall H -U., Einarsson C. Gallstone disease. Journal of Internal Medicine. 2007; 261: 529–542.
https://doi.org/10.1111/j.1365-2796.2007.01783.x PMID: 17547709
2. Stinton LM, Shaffer EA. Epidemiology of Gallbladder Disease: Cholelithiasis and Cancer. Gut Liver.
2012; 6: 172–187. https://doi.org/10.5009/gnl.2012.6.2.172 PMID: 22570746
3. Shabanzadeh DM. Incidence of gallstone disease and complications. Curr Opin Gastroenterol. 2018;
34: 81–89. https://doi.org/10.1097/MOG.0000000000000418 PMID: 29256915
4. Everhart JE, Ruhl CE. Burden of Digestive Diseases in the United States Part III: Liver, Biliary Tract,
and Pancreas. Gastroenterology. 2009; 136: 1134–1144. https://doi.org/10.1053/j.gastro.2009.02.038
PMID: 19245868
5. Fujita N, Yasuda I, Endo I, Isayama H, Iwashita T, Ueki T, et al. Evidence-based clinical practice guide-
lines for cholelithiasis 2021. J Gastroenterol. 2023; 58: 801–833. https://doi.org/10.1007/s00535-023-
02014-6 PMID: 37452855
6. Park Y, Kim D, Lee JS, Kim YN, Jeong YK, Lee KG, et al. Association between diet and gallstones of
cholesterol and pigment among patients with cholecystectomy: a case-control study in Korea. J Health
Popul Nutr. 2017; 36: 39. https://doi.org/10.1186/s41043-017-0116-y PMID: 29169372
7. Chang C-M, Chiu THT, Chang C-C, Lin M-N, Lin C-L. Plant-Based Diet, Cholesterol, and Risk of Gall-
stone Disease: A Prospective Study. Nutrients. 2019; 11: 335. https://doi.org/10.3390/nu11020335
PMID: 30720747
8. McConnell TJ, Appleby PN, Key TJ. Vegetarian diet as a risk factor for symptomatic gallstone disease.
Eur J Clin Nutr. 2017; 71: 731–735. https://doi.org/10.1038/ejcn.2016.252 PMID: 28272400
9. Kim J, Kim H, Giovannucci EL. Plant-based diet quality and the risk of total and disease-specific mortal-
ity: A population-based prospective study. Clin Nutr. 2021; 40: 5718–5725. https://doi.org/10.1016/j.
clnu.2021.10.013 PMID: 34749131
10. Chen H, Shen J, Xuan J, Zhu A, Ji JS, Liu X, et al. Plant-based dietary patterns in relation to mortality
among older adults in China. Nat Aging. 2022; 2: 224–230. https://doi.org/10.1038/s43587-022-00180-
5 PMID: 37118372
11. Satija A, Bhupathiraju SN, Rimm EB, Spiegelman D, Chiuve SE, Borgi L, et al. Plant-Based Dietary Pat-
terns and Incidence of Type 2 Diabetes in US Men and Women: Results from Three Prospective Cohort
Studies. PLoS Med. 2016; 13: e1002039. https://doi.org/10.1371/journal.pmed.1002039 PMID:
27299701
12. Mokhtari E, Rouhani P, Shahdadian F, Mohammadi S, Heidari Z, Saneei P. An Unhealthy Plant-Based
Diet Increases Risk of Hypertension but not Framingham Risk Score in Adults. Curr Dev Nutr. 2023; 7:
102008. https://doi.org/10.1016/j.cdnut.2023.102008 PMID: 37869525
13. Kim H, Caulfield LE, Rebholz CM. Healthy Plant-Based Diets Are Associated with Lower Risk of All-
Cause Mortality in US Adults. The Journal of Nutrition. 2018; 148: 624–631. https://doi.org/10.1093/jn/
nxy019 PMID: 29659968

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 10 / 11

PLOS ONE Plant-based dietary index and gallstone disease

14. Walcher T, Haenle MM, Mason RA, Koenig W, Imhof A, Kratzer W, et al. The effect of alcohol, tobacco
and caffeine consumption and vegetarian diet on gallstone prevalence. Eur J Gastroenterol Hepatol.
2010; 22: 1345–1351. https://doi.org/10.1097/MEG.0b013e32833efdb2 PMID: 20802339
15. Jayanthi V, Anand L, Ashok L, Srinivasan V. Dietary factors in pathogenesis of gallstone disease in
southern India—a hospital-based case-control study. Indian J Gastroenterol. 2005; 24: 97–99. PMID:
16041099
16. Lim HK, Luben R, Hart AR, Banim PJ. P255 Dietary niacin intake is inversely associated with the devel-
opment of gallstones: a prospective cohort study. Posters. BMJ Publishing Group Ltd and British Soci-
ety of Gastroenterology; 2021. p. A173.3-A174.
17. Tsai C-J, Leitzmann MF, Willett WC, Giovannucci EL. Dietary carbohydrates and glycaemic load and
the incidence of symptomatic gall stone disease in men. Gut. 2005; 54: 823–828. https://doi.org/10.
1136/gut.2003.031435 PMID: 15888792
18. Ortega RM, Fernández-Azuela M, Encinas-Sotillos A, Andrés P, López-Sobaler AM. Differences in diet
and food habits between patients with gallstones and controls. J Am Coll Nutr. 1997; 16: 88–95. https://
doi.org/10.1080/07315724.1997.10718655 PMID: 9013440
19. Barré A, Gusto G, Cadeau C, Carbonnel F, Boutron-Ruault M-C. Diet and Risk of Cholecystectomy: A
Prospective Study Based on the French E3N Cohort. Am J Gastroenterol. 2017; 112: 1448–1456.
https://doi.org/10.1038/ajg.2017.216 PMID: 28741614
20. Sadri Z, Harouni J, Vahid F, Khosravani Z, Najafi F. Association between the Dietary Inflammatory
Index with gallstone disease: finding from Dena PERSIAN cohort. BMJ Open Gastroenterol. 2022; 9:
e000944. https://doi.org/10.1136/bmjgast-2022-000944 PMID: 36123004
21. Liu Z, Kemp TJ, Gao Y-T, Corbel A, McGee EE, Wang B, et al. Association of circulating inflammation
proteins and gallstone disease. J Gastroenterol Hepatol. 2018; 33: 1920–1924. https://doi.org/10.1111/
jgh.14265 PMID: 29671891
22. Medawar E, Huhn S, Villringer A, Veronica Witte A. The effects of plant-based diets on the body and the
brain: a systematic review. Transl Psychiatry. 2019; 9: 226. https://doi.org/10.1038/s41398-019-0552-0
PMID: 31515473
23. Fresán U, Sabaté J. Vegetarian Diets: Planetary Health and Its Alignment with Human Health. Adv
Nutr. 2019; 10: S380–S388. https://doi.org/10.1093/advances/nmz019 PMID: 31728487
24. Tilman D, Clark M. Global diets link environmental sustainability and human health. Nature. 2014; 515:
518–522. https://doi.org/10.1038/nature13959 PMID: 25383533

PLOS ONE | https://doi.org/10.1371/journal.pone.0305822 June 25, 2024 11 / 11