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The relationship between
urinary glyphosate and all-cause
and specic-cause mortality: a
prospective study
Yi Chen1,2, Zhijian Wu1,2, Meng Li1 & Yanqing Wu1
Glyphosate (GLY) is a well-known herbicide with signicant applications in both agriculture and
non-agriculture. However, GLY overuse in recent years has resulted in detection of GLY residues in
many crops, endangering human health and food safety. Our aim is to investigate the relationship
between urinary GLY and mortality, as well as its inuencing factors. The National Health and Nutrition
Examination Survey (NHANES) data from 4740 American adults were examined. Fitted smooth curves,
generalized summation models, and multiple logistic regression models were used to investigate the
relationship between urinary GLY and mortality. To investigate potential regulatory elements between
the two eects, perform subgroup analysis. During a median follow-up of 4.03 years, there were a total
of 238 all-cause deaths, 75 cardiovascular disease (CVD) deaths and 52 cancer deaths. The urinary GLY
is positively correlated with all-cause mortality. Each 1 ng/ml increase in urinary GLY was associated
with a 40% increased risk of all-cause mortality (Hazard ratio (HR) 1.40, 95% condence interval (CI)
1.09–1.80), and an 50% increased risk of all-cause mortality in High group compared with Low group
(HR 1.50, 95% CI 1.05–2.14). In subgroup analysis, the association between urinary GLY and all-cause
mortality was signicantly modied by gender (P for interaction = 0.03), and the association between
urinary GLY and cancer mortality was signicantly modied by hypertension (P for interaction = 0.022).
Higher urinary GLY seems to be associated with more all-cause death, and gender may aect this
association. Furthermore, urine GLY may have a higher eect on cancer mortality in people without
hypertension.
Keywords Glyphosate, All-cause mortality, Cardiovascular mortality, Cancer mortality, NHANES
Glyphosate (GLY) is the most widely used herbicide in the US agricultural sector1. It inhibits the 5-enolacetone
shikimic acid-3-phosphate synthase (EPSPS), which interferes with the formation of aromatic amino acids and
ultimately causes plant death in plants by acting on the shikimic acid pathway in plants2,3. Currently, farms,
orchards, and gardens utilize it primarily for weeding1,4. However, because of the exponential increase in GLY
use over the past century, its presence has been found in a wide range of foods3,5–9. As its use continues to
rise, the public and scientic community are paying more and more attention to GLY’s possible eects on
human health. Several investigations have revealed that GLY is not as safe and innocuous as rst thought. GLY
can strongly irritate human skin, eyes, and respiratory tracts during acute exposure, resulting in discomfort
sensations10–12. Even more concerning are the long-term health concerns associated with exposure, which
can disrupt the endocrine system, alter hormone balance, and negatively impact vital physiological functions
including development and reproduction13,14. GLY may be carcinogenic, as evidenced by some research that
have connected it to an increased risk of cancer15,16. Furthermore, GLY may harm the cardiovascular system,
immune system, the nervous system, the liver, kidneys, et17–20. In 2015, GLY was categorized as a chemical that
was “potentially carcinogenic to humans” by the World Health Organization’s International Agency for Research
on Cancer (IARC)1,21,22. Furthermore, extensive and prolonged usage of GLY may have detrimental eects on
aquatic and soil species23–26. Moreover, GLY usage over an extended period of time may cause weed resistance27,28.
Higher doses of GLY or other herbicides are required to suppress weeds that have developed resistance to GLY,
which increases agricultural production costs and strains the environment29. On the other hand, GLY is not
1Department of Cardiology, The Second Aliated Hospital, Jiangxi Medical College, Nanchang
University, Nanchang 330006, China. 2Yi Chen and Zhijian Wu contributed equally to this work. email:
m13657004331@163.com; wuyanqing01@sina.com
OPEN
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expected to cause cancer, according to the ndings of the Joint Meeting on Pesticide Residues between the Food
and Agriculture Organization (FAO) and the World Health Organization (WHO)30. e U.S. EPA came to the
conclusion that there was “inadequate information to assess carcinogenic potential,” “carcinogenic to humans,”
or “likely to be carcinogenic to humans,” based on the weight of the evidence and available data31,32. In a similar
vein, the Glyphosate Assessment Group of the European Union declared that, when used in accordance with
recommended usage, GLY is safe for all purposes and suggested declassifying it as carcinogenic33. erefore,
opinions on GLY’s safety are currently divided. Nonetheless, it is easy to conclude from the rst two NHANES
cycles’ data that GLY exposure is common among Americans and that most people’s urine contains GLY34,35.
Here, we examined the relationship between urine GLY and adult mortality in America by extracting data on
urinary GLY and all-cause and cardiovascular mortality from the National Health and Nutrition Examination
Surveys (NHANES) conducted from 2013 to 2018.
Methods
Study design and population
National Health and Nutrition Examination Survey (NHANES) is a cross-sectional study conducted by the U.S.
Centers for Disease Control and Prevention (CDC). NHANES utilizes a complex, multistage sampling design
designed to be representative of the nation’s diverse population groups. e data collected include physical
examinations, interviews, and laboratory tests that help researchers analyze health trends and inform public
health policy. Ethical approval for the study was obtained from the National Center for Health Statistics (NCHS)
Ethics Review Board, and all NHANES participants provided written informed consent. e data collected
and related documents are publicly available. For more information, please visit the ocial NHANES website.
In addition to the core survey, NHANES links participant data to the National Death Index (NDI) to track
mortality outcomes. NDI mortality data are available at h t t p s : / / w w w . c d c . g o v / n c h s / d a t a - l i n k a g e / m o r t a l i t y . h t m.
We conducted a secondary analysis using data from three independent NHANES cycles between 2013 and
2018 to investigate the association between GLY exposure and all-cause and cardiovascular mortality. A total
of 8,507 participants with available urinary GLY data were included for the study. Due to the vulnerability of
children and adolescents, we excluded 3,109 participants under the age of 18. Next, we excluded 17 participants
with missing mortality data and 641 participants with missing urinary GLY data. In the end, 4,740 eligible
individuals were included in the nal analysis (Fig.1).
Urinary GLY
In the NHANES, urinary GLY measurements are part of the environmental exposure data collected to assess
the levels of this widely used herbicide in the U.S. population. e eligible sample consisted of all examined
participants aged 3 to 5 years and one-third of the examined participants aged 6 years and older. NHANES’s
ocial website provides information about urinary GLY’s range and handling options. e median GLY level
in the population’s urine serves as the grouping concentration for the independent variables. Urinary GLY was
measured by using 200µl of urine and was based on 2D-on-line ion chromatography coupled with tandem mass
spectrometry (IC-MS/MS) and isotope dilution quantication36. e analytical measurements were conducted
following strict quality control/quality assurance CLIA guidelines. Along with the study samples, each analytical
run included high- and low-concentration quality control materials (QCMs) and reagent blanks to assure
the accuracy and reliability of the data. e concentrations of the high-concentration QCMs and the low-
concentration QCMs, averaged to obtain one measurement of high-concentration QCM and low-concentration
QCM for each run, were evaluated using standard statistical probability rules37.
All-cause, cardiovascular mortality and cancer mortality
In this study, the outcome variables included all-cause mortality, cardiovascular mortality and cancer mortality.
ese mortality data were obtained through linkage with the NDI38. Specically, participants without a recorded
death were considered alive during the follow-up period, which extended from the time of their participation
in the survey until December 31, 2019. All-cause mortality encompasses deaths from any cause. Cardiovascular
mortality was dened using the International Classication of Diseases, 10th Revision (ICD-10) codes: I00-I09,
I11, I13, I20-I51, and I60-I69, which represent a range of cardiovascular-related conditions, including heart
disease, hypertensive heart disease, and cerebrovascular disease. Cancer mortality include any death brought
on by cancer.
Potential covariates
e covariates in this study were pre-selected based on prior research identifying risk factors for all-cause
mortality. Aer variable screening, the nal multivariable logistic regression analysis included the following
covariates: Continuous variables include age, poverty-to-income ratio (PIR), body mass index (BMI, kg/m²),
alanine aminotransferase (ALT, U/L), serum creatinine (SCR, µmol/L), blood urea nitrogen (BUN, mg/dL),
estimated glomerular ltration rate (eGFR, mL/min/1.73m²), uric acid (UA, µmol/L), fasting blood glucose
(FBG, mmol/L), glycated hemoglobin (HbA1c, %), total cholesterol (TC, mmol/L), and triglycerides (TG,
mmol/L); Categorical variables include sex, ethnicity, education level, smoking and drinking status, physical
activity, presence of hypertension, and presence of diabetes. e eGFR was calculated using the Chronic Kidney
Disease Epidemiology Collaboration (CKD-EPI) equation: eGFR = 141 × min(SCR/κ, 1)α × max(SCR/κ, 1)-
1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black], κ is 0.7 for females and 0.9 for males, α is -0.329 for
females and − 0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum
of Scr/κ or 139. Hypertension was dened as either a self-reported diagnosis from a healthcare professional, a
systolic blood pressure ≥ 140 mmHg, and/or diastolic blood pressure ≥ 90 mmHg40. Diabetes was dened as a
self-reported diagnosis, a fasting blood glucose (FBG) ≥ 7 mmol/L, or HbA1c > 6.5%41.
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Statistical analysis
All statistical analyses in this study were conducted following the CDC guidelines for NHANES data analysis ( h
t t p s : / / w w w n . c d c . g o v / n c h s / n h a n e s / t u t o r i a l s / d e f a u l t . a s p x), with each NHANES participant assigned a sampling
weight to ensure the representativeness of the data42. To compare baseline characteristics across tertiles of urinary
GLY levels, continuous variables were analyzed using weighted linear regression models and presented as means
with 95% condence intervals (CI), while categorical variables were analyzed using weighted chi-squared tests
and reported as counts and percentages. e relationship between urinary GLY and mortality (both all-cause and
cardiovascular) was evaluated using univariate and multivariate Cox proportional hazards regression models.
ree models were constructed: model 1: Unadjusted, model 2: Adjusted for sociodemographic factors, and
model 3: Adjusted for all covariates listed in Table1. To account for potential nonlinear relationships between
urinary GLY levels and mortality, cubic spline functions and smooth curve tting (penalized spline method) were
applied in Cox regression models. e Kaplan-Meier method was employed to plot survival curves, comparing
mortality rates across dierent GLY exposure groups. e Log-rank test was used to assess statistical dierences
between the survival curves. In addition to the main analyses, stratied analyses and interaction tests were
conducted to assess the potential modifying eects of various covariates on the relationship between urinary
GLY levels and mortality. e following variables were included for stratication: age (< 60 vs. ≥60 years), sex
(man vs. woman), race (Mexican American vs. Other Hispanic vs. Non-Hispanic White vs. Non-Hispanic Black
vs. other race), educational attainment (< 9th grade vs. 9-11th grade vs. high school vs. college vs. graduate and
above), BMI (< 25 vs. ≥25kg/m2), smoking status (never vs. quit vs. current), alcohol consumption (never vs.
1 ~ 5 drinks/month vs. 5 ~ 10 drinks/month vs. >10 drinks/month vs. unknown), and eGFR (< 60 vs. ≥60 mL/
min/1.73 m2), hypertension (yes vs. no), and diabetes (yes vs. no).
To maximize statistical power and reduce potential bias from excluding observations with missing covariate
data, we employed a robust approach to handle missing values. Multiple imputation was used for continuous
Fig. 1. Flow chart of participants.
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Characteristics NbMissing c
Glyphosate (ng/mL, Urine)
P-valueLow group (< 0.33) High group (0.33–8.21)
N a2368 2372
Sex 723,907,169 0 < 0.001
Male 45.39 (43.13 ,47.68) 51.62 (48.28 ,54.95)
Female 54.61 (52.32 ,56.87) 48.38 (45.05 ,51.72)
Age, years 723,907,169 0 45.88 (44.86 ,46.90) 48.05 (47.11 ,48.98) 0.001
Race, % 723,907,169 0 < 0.001
Mexican American 9.83 (7.60 ,12.62) 8.02 (6.07 ,10.53)
Other Hispanic 6.90 (5.40 ,8.79) 6.22 (4.90 ,7.87)
Non-Hispanic White 62.40 (58.26 ,66.36) 65.01 (60.44 ,69.32)
Non-Hispanic Black 10.07 (8.07 ,12.50) 12.79 (10.21 ,15.92)
Other race 10.81 (8.92 ,13.03) 7.96 (6.85 ,9.23)
Education level, % 723,907,169 0 0.467
< 9th grade 4.22 (3.47 ,5.13) 4.53 (3.72 ,5.51)
9–11th grade 7.99 (6.65 ,9.57) 9.23 (7.44 ,11.40)
High school 22.90 (20.29 ,25.75) 22.76 (20.53 ,25.16)
College 31.96 (28.89 ,35.20) 33.21 (30.37 ,36.17)
Graduate or above 32.92 (28.47 ,37.70) 30.27 (27.25 ,33.46)
PIR 669,181,295 54,725,874 3.11 (2.99 ,3.23) 2.94 (2.80 ,3.08) 0.031
Physical Activity d723,907,169 0 0.597
Inactive 44.38 (41.65 ,47.15) 46.46 (42.59 ,50.37)
Moderately active 32.52 (29.48 ,35.72) 31.40 (28.37 ,34.60)
Highly active 23.10 (20.81 ,25.55) 22.14 (19.69 ,24.80)
Smoking Status, % 723,907,169 0 0.644
Never Smoking 58.52 (55.46 ,61.52) 57.65 (54.84 ,60.42)
Quit Smoking 19.99 (17.74 ,22.43) 20.85 (18.81 ,23.04)
Current Smoking 21.49 (19.18 ,24.00) 21.44 (19.25 ,23.81)
Unknow 0.00 (0.00 ,0.00) 0.06 (0.01 ,0.28)
Drinking status, % 723,907,169 0 < 0.001
Never Drinking 13.41 (10.41 ,17.12) 17.44 (15.35 ,19.74)
1–5 drinks/month 27.22 (24.22 ,30.43) 34.36 (31.76 ,37.07)
5–10 drinks/month 4.76 (3.90 ,5.79) 6.16 (5.04 ,7.51)
10 + drinks/month 9.95 (7.38 ,13.27) 11.31 (9.50 ,13.41)
Unknown 44.67 (40.12 ,49.31) 30.73 (27.47 ,34.20)
BMI e, kg/m2720,018,844 3,888,325 28.96 (28.53 ,29.39) 29.67 (29.21 ,30.14) 0.009
Hypertension f, % 723,907,169 0 0.033
No 64.92 (61.71 ,67.99) 60.92 (58.30 ,63.47)
Yes 35.08 (32.01 ,38.29) 39.08 (36.53 ,41.70)
Diabetes g, % 723,907,169 0 < 0.001
No 90.44 (89.19 ,91.56) 85.13 (83.13 ,86.93)
Yes 9.56 (8.44 ,10.81) 14.87 (13.07 ,16.87)
ALT, U/L 699,645,877 24,261,292 23.81 (23.06 ,24.56) 25.08 (23.97 ,26.19) 0.053
SCR, umol/ 699,593,948 24,313,221 75.66 (74.51 ,76.82) 79.61 (78.31 ,80.91) < 0.001
BUN, mg/dL 699,304,649 24,602,520 4.90 (4.80 ,5.01) 5.29 (5.17 ,5.42) < 0.001
eGFR h699,593,948 24,313,221 96.65 (95.23 ,98.07) 93.38 (92.17 ,94.59) < 0.001
UA, umol/L 699,134,538 24,772,632 320.28 (315.50 ,325.05) 321.58 (316.76 ,326.40) 0.684
Continued
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variables, ensuring that the missing data were replaced with plausible values based on other available information.
For categorical variables, dummy variables were introduced to account for missing data. All statistical analyses
were conducted using R soware (version 4.2.2) and EmpowerStats (http://www.empowerstats.com, X&Y
Solutions, Inc., Boston, MA). A two-sided P-value < 0.05 was considered statistically signicant.
Results
Baseline characteristics of the study population
Overall, this study included 4740 individuals (median follow-up time: 4.03 years) (Fig.1). e social demographic
characteristics and other covariates of the selected participants are shown in Table1. e ranges of urinary GLY
content for the two groups are < 0.33 and 0.33-8.21ng/mL, respectively. Except for education level, physical
activity, smoking status, ALT, UA and Triglyceride, there were signicant statistical dierences between both
groups for all included characteristics. Compared to the low group, the high group participants are more likely
to be male, older, non-Hispanic white and black and have a history of hypertension and diabetes, have lower
levels of PIR, eGFR, TC and HDL-C; and have a higher level of more than 10 drinks per month, BMI, SCR, BUN,
FBG and HbA1c.
Association of urinary GLY with all-cause, cardiovascular mortality and cancer mortality
As indicated by Table2 and Table S1, there were 238 deaths from all causes, 75 deaths from cardiovascular disease
and 52 deaths from cancer during the follow-up period of 19,092.33 person-years. We constructed three models
to analyze the independent role of urinary GLY in all-cause, cardiovascular mortality and cancer mortality.
Overall, regardless of adjusting for confounding factors, the urinary GLY of all participants was signicantly
positively correlated with all-cause mortality. In the unadjusted model, the all-cause mortality increased by 49%
with each 1 ng/mL increase in the urinary GLY (HR 1.49, 95% CI 1.24–1.79). is positive relationship in
Model 2 (HR 1.31, 95% CI 0.99–1.71) and Model 3 (HR 1.40, 95% CI 1.09–1.80) remained robust aer adjusting
for the confounding factors. All-cause mortality was signicantly higher in the High group as compared to
the Low group. In Model 3, the corresponding HRs for all-cause mortality was 1.50 (95% CI, 1.05–2.14).
Moreover, in Model 1, mortality from cardiovascular disease was positively correlated with urinary GLY, with
corresponding mortality HRs of 1.44 (95% CI, 1.21–1.71). While the eect values in Models 2 and 3 were still
more prominent and the association’s direction remained constant across all models, the relationships in those
models did not attain statistical signicance. Adjusting for additional factors may have diminished statistical
signicance, but generally the association between cardiovascular mortality and urinary GLY appears to be
robust. Cancer mortality and urine GLY had a neutral correlation in Model 1, with corresponding mortality
HRs of 1.07 (95% CI, 0.67–1.72) 0.775. Although not statistically signicant, there was a negative connection
between cancer mortality and urine GLY in Models 2 and 3, with corresponding mortality HRs of 0.66 (95% CI,
0.37–1.18) and 0.77 (95% CI, 0.42–1.44). We reanalyzed the relationship between urinary GLY and mortality
using post-interpolation data, and the results were not qualitatively dierent (Table3 and Table S2). e fully
adjusted smooth curve tting results also support the prior ndings (Fig.2 and Figure S1). Additionally, we
Characteristics NbMissing c
Glyphosate (ng/mL, Urine)
P-valueLow group (< 0.33) High group (0.33–8.21)
TC, mmol/L 699,423,837 24,483,333 5.06 (4.98 ,5.13) 4.89 (4.83 ,4.95) < 0.001
Triglyceride, mmol/L 700,624,321 23,282,848 1.68 (1.57 ,1.80) 1.71 (1.64 ,1.77) 0.681
HDL-C, mmol/L 702,434,526 21,472,643 1.43 (1.40 ,1.47) 1.36 (1.34 ,1.39) < 0.001
FBG, mmol/L 699,356,578 24,550,591 5.39 (5.32 ,5.45) 5.74 (5.64 ,5.84) < 0.001
HbA1c, % 707,770,890 16,136,279 5.56 (5.52 ,5.59) 5.73 (5.68 ,5.77) < 0.001
Tab le 1. Characteristics of study population. Continuous variables were described by means (95%CI) and
P-values were calculated by weighted linear regression model. Categorical variables were described by
percentages (95%CI) and P-values was calculated by weighted Chi-square test. PIR poverty income ratio,
BMI body mass index, ALT alanine aminotransferase, SCR serum creatinine, BUN blood urea nitrogen,
eGFR estimated glomerular ltration rate, UA uric acid, TC total cholesterol, HDL-C high density lipoprotein
cholesterol, FBG fasting blood glucose, HbA1c hemoglobin A1c. a Unweighted number of observations in
dataset, b Weighted number, c Weighted number of missing data. d Inactive is dened as engaging in no
moderate- or vigorous-intensity physical activity; Moderately active refers to engaging in moderate- or
vigorous-intensity physical activity for more than 10min on 1 to 3 days per week; Highly active is dened
as engaging in moderate- or vigorous-intensity physical activity for more than 10min on 4 to 7 days per
week. e BMI was calculated as the body weight in kilograms divided by the square of the height in meters. f
Hypertension was dened by ≥ 1 of the following criteria: systolic blood pressure ≥ 140mm Hg or diastolic
blood pressure ≥ 90 or self-reported physician diagnosis of hypertension. g. Diabetes was dened as self-
reported physician diagnosis of diabetes or a fasting glucose concentration > 126mg/dL. h Estimated using the
newly developed Chronic Kidney Disease Epidemiology Collaboration equation: eGFR = 141 × min(SCR/κ, 1)α
× max(SCR/κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black], where Scr is serum creatinine, κ is 0.7 for
females and 0.9 for males, α is -0.329 for females and − 0.411 for males, min indicates the minimum of Scr/κ or
1, and max indicates the maximum of Scr/κ or 1.
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investigated urinary GLY’s threshold eect analysis on all-cause mortality, cardiovascular mortality and cancer
mortality (Table4 and Table S3). To t the relationship between urinary GLY and mortality, we employed the
Cox proportional hazards model and the 2-segment Cox proportional hazards model, respectively. Table4 and
Table S3 demonstrates a linear correlation between urinary GLY and all-cause mortality, but not with urinary
GLY and cardiovascular mortality and cancer mortality (P < 0.05 for the log likelihood ratio test). We discovered
that urinary GLY has an inection point of 0.38 ng/mL. When urinary GLY < 0.38 ng/mL, an increase in urinary
GLY is substantially associated with an increased risk of cardiovascular mortality (HR = 73.08; 95% CI, 2.12-
2523.35; P = 0.018). Conversely, when urinary GLY > 0.38 ng/mL, there is no statistically signicant association
between increased urinary GLY and cardiovascular mortality. Furthermore, the results of the unadjusted Kaplan
Meier curve indicated that the High group had a higher risk of all-cause, cardiovascular mortality and cancer
mortality as compared to the Low group (Fig.3 and Figure S2).
Glyphosate
(ng/mL, urine)
HR (95% CI) a
MI.1 MI.2 MI.3 MI.4 MI.5
Model 1 Model 2 Mode l 1 Model 2 Mo del 1 Model 2 Model 1 Mo del 2 Model 1 Mode l 2
All-cause mortality
Continuous 1.49 (1.24–1.79) 1.31
(1.02–1.69) 1.49
(1.24–1.79) 1.33
(1.03–1.72) 1.49
(1.24–1.79) 1.35
(1.05–1.74) 1.49
(1.24–1.79) 1.33
(1.03–1.72) 1.49
(1.24–1.79)
1.34
(1.05–
1.72)
Low group reference reference reference reference reference reference reference reference reference reference
High group 1.77 (1.28–2.44) 1.39
(1.01–1.93) 1.77
(1.28–2.44) 1.39
(1.01–1.91) 1.77
(1.28–2.44) 1.41
(1.04–1.92) 1.77
(1.28–2.44) 1.39
(1.01–1.91) 1.77
(1.28–2.44)
1.37
(1.00-
1.90)
Cardiovascular mortality
Continuous 1.44 (1.21–1.71) 1.10
(0.84–1.45) 1.44
(1.21–1.71) 1.16
(0.90–1.50) 1.44
(1.21–1.71) 1.15
(0.89–1.47) 1.44
(1.21–1.71) 1.14
(0.87–1.48) 1.44
(1.21–1.71)
1.16
(0.90–
1.50)
Low group reference reference reference reference reference reference reference reference reference reference
High group 3.06 (1.38–6.78) 1.99
(0.81–4.89) 3.06
(1.38–6.78) 2.03
(0.86–4.81) 3.06
(1.38–6.78) 2.05
(0.86–4.86) 3.06
(1.38–6.78) 2.00
(0.85–4.74) 3.06
(1.38–6.78)
2.04
(0.85–
4.86)
Tab le 3. Association of urine glyphosate with All-cause and cardiovascular mortality based on multiple
imputed data. a Weighted Cox proportional hazards models were used to estimate HRs and 95% CIs. Model
1: adjusted for none. Model 2 adjusted for sex, age, race, education status, PIR, smoking and drinking status,
Physical Activity, hypertension and diabetes, BMI, ALT, SCR, eGFR, UA, TC, Triglyceride, FBG, and HbA1c.
HR hazard ratio, CI condence interval, PIR poverty income ratio, BMI body mass index, ALT alanine
aminotransferase, SCR Serum creatinine, BUN blood urea nitrogen, eGFR estimated glomerular ltration rate,
UA uric acid, TC total cholesterol, FBG fasting blood glucose, HbA1c hemoglobin A1c.
Glyphosate
(ng/mL, urine) Person-y No. of events Mortality rate (per 1000 person-y)
Adjusted HR (95% CI) a, P Val ue
Model 1 Model 2 Model 3
All-cause mortality
Continuous 19,092.33 238 12.47 1.49 (1.24–1.79) < 0.001 1.31 (0.99–1.71) 0.055 1.40 (1.09–1.80) 0.008
Low group 8,761.60 86 9.82 reference reference reference
High group 9,972.28 152 15.24 1.77 (1.28-2,44) < 0.001 1.38 (0.98–1.95) 0.066 1.50 (1.05–2.14) 0.026
Cardiovascular mortality
Continuous 19,092.33 75 3.93 1.44 (1.21–1.71) < 0.001 1.11 (0.83–1.48) 0.491 1.16 (0.89–1.52) 0.278
Low group 8,761.60 20 2.28 reference reference reference
High group 9,972.28 55 5.52 3.06 (1.38–6.78) 0.006 2.11 (0.84–5.31) 0.112 2.00 (0.72–5.53) 0.181
Tab le 2. Association of urine glyphosate with All-cause and cardiovascular mortality. Model 1: adjusted for
none. Model 2: adjusted for sex, age, race, education status, and PIR. Model 3: adjusted for sex, age, race,
education status, PIR, smoking and drinking status, Physical Activity, hypertension and diabetes, BMI, ALT,
SCR, eGFR, UA, TC, Triglyceride, FBG, and HbA1c. HR hazard ratio, CI condence interval, PIR poverty
income ratio, BMI body mass index, ALT alanine aminotransferase, SCR Serum creatinine, BUN blood urea
nitrogen, eGFR estimated glomerular ltration rate, UA uric acid, TC total cholesterol, FBG fasting blood
glucose, HbA1c hemoglobin A1c. aWeighted Cox proportional hazards models were used to estimate HRs and
95% CIs.
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Subgroup analyses
We stratied the primary covariates and performed subgroup analysis to further conrm the results’ reliability
in the presence of confounding variables and to determine whether there are any factors that could change the
connection between urinary GLY and mortality. Other than gender and hypertension, no other covariates—
such as age, PIR, diabetes, BMI, and eGFR—had a statistically signicant eect on the association between GLY
and mortality (all p interactions > 0.05) (Fig.4 and Figure S3). e signicant interaction (p-value of 0.03 for
the interaction) was found between all-cause mortality and sex, suggesting that sex may be an important factor
inuencing the eects of urinary GLY, with female detriment the most (HR 1.59, 95% CI 1.20–2.10). Cancer
mortality and hypertension have a signicant interaction (p-value of 0.022 for the interaction), indicating that
urine GLY may have a greater impact on cancer mortality in persons without hypertension (HR 2.31, 95%
CI 0.87–6.13). e urinary GLY eects, nevertheless, were highly consistent for other important factors, such
as age, PIR, diabetes, BMI, and eGFR subgroups; none of the interaction eects, however, reached statistical
signicance (P for all interactions > 0.05).
Discussion
In this large prospective analysis, we discovered a strong positive connection between urinary GLY and all-
cause mortality, which persisted even aer controlling for confounding variables. Furthermore, we discovered
that the relationship between urinary GLY and all-cause mortality may vary depending on a person’s sex in the
stratication and interaction study. e ndings demonstrated a substantial positive correlation between the
urinary GLY by female individuals and all-cause mortality, but not a signicant correlation between the urinary
GLY by male individuals and all-cause mortality.
GLY is an ecient and broad-spectrum herbicide29. It works well in elds with a variety of crops, including
cotton, corn, soybeans, etc5,43,44. Broad-leaved weeds like amaranth, quinoa, and purslane, as well as annual
and perennial weeds like barnyard grass, sagebrush, cowweed, and horseweed, can all be successfully prevented
Adjusted HR (95% CI) a, P Val ue
All-cause mortality Cardiovascular mortality
Fitting by standard Cox proportional hazards model 1.47 (1.08, 2.00) 0.014 1.41 (0.86, 2.30) 0.176
Fitting by 2-piecewise Cox proportional hazards model
Inection point 0.57 0.38
< Inection point 2.47 (0.81, 7.56) 0.113 73.08 (2.12, 2523.35) 0.018
> Inection point 1.26 (0.80, 1.98) 0.319 0.95 (0.51, 1.78) 0.874
Log likelihood ratio 0.344 0.019
Tab le 4. reshold eect analysis of urine glyphosate on All-cause and cardiovascular mortality in US adults.
Adjust for adjusted for sex, age, race, education status, PIR, smoking and drinking status, physical activity,
hypertension and diabetes, BMI, ALT, SCR, eGFR, UA, TC, Triglyceride, FBG, and HbA1c. HR hazard ratio,
CI condence interval, PIR poverty income ratio, BMI body mass index, ALT alanine aminotransferase, SCR
Serum creatinine, BUN blood urea nitrogen, eGFR estimated glomerular ltration rate, UA uric acid, TC total
cholesterol, FBG fasting blood glucose, HbA1c hemoglobin A1c. aCox proportional hazards models were used
to estimate HRs and 95% CIs.
Fig. 2. Kaplan–Meier survival curve for mortality by glyphosate (weighted and unadjusted). (A) All-cause
mortality, (B) Cardiovascular mortality.
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and controlled by it45–48. GLY can be used before to planting or during crop growth to enhance crop quality
and production by establishing a conducive growing environment49. Additionally, GLY works well against
some harmful plants that are hard to eradicate, such reeds, tiny ying awns, etc50,51. Furthermore, GLY nds
extensive use in horticulture, forestry, and other domains52,53. However, GLY has been abused precisely because
of its potent weed control action. Extensive and prolonged use of GLY may alter the diversity and activity of
soil microbes, diminish soil fertility, and harm soil structure54–56. GLY may be dangerous to aquatic life if it
gets into a body of water57,58. Elevated levels of GLY have the potential to impede the development of aquatic
Fig. 4. Stratifying analyses by potential modiers of the association between glyphosate and all-cause
mortality and cardiovascular mortality. Each subgroup analysis adjusted for sex, age, PIR, BMI, hypertension
and diabetes and eGFR except for the stratifying variable.
Fig. 3. Association between glyphosate and all-cause and cardiovascular mortality. (A) All-cause mortality, (B)
Cardiovascular mortality. e solid and dotted lines represent the estimated values and their corresponding
95% condence intervals, respectively. Adjustment factors included sex, age, race, education status, PIR,
physical activity, smoking and drinking status, BMI, hypertension and diabetes, ALT, SCR, BUN, eGFR,
UA, TC, TG, HDL-C, FBG, and HbA1c. PIR poverty income ratio, BMI body mass index, ALT alanine
aminotransferase, SCR Serum creatinine, BUN blood urea nitrogen, eGFR estimated glomerular ltration rate,
UA uric acid, TC total cholesterol, TG triglycerideHDL-C high density lipoprotein cholesterol, FBG fasting
blood glucose, HbA1c hemoglobin A1c.
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vegetation and impact the equilibrium of aquatic environments59,60. Fish and shellsh are examples of aquatic
species that may be toxically aected by GLY61–63. Furthermore, while gathering nectar and pollen, insects like
bees and butteries may come into contact with GLY and become poisoned as a result64–67. In northwestern
Germany, Liebing et al. discovered that two-thirds of the examined samples for Phasianus colchicus hens that
were free-ranged showed positive results for GLY68. A retrospective analysis of all suspected cases of livestock
poisoning revealed that GLY was the cause in cases involving dogs, cats, horses, goats, and sheep69. Moreover, it
is important to consider how GLY aects aquatic organisms, as we have previously mentioned. Agbohesi et al.
discovered that GLY damages the liver of Clarias gariepinus, an African catsh70. According to Ames et al., GLY
can harm zebrash embryonic larvae, resulting in teratogenicity, heart defects, and even death71. When adult
zebrash exposed to GLY, Sulukan et al. observed that the progeny had decreased blood ow and heart rate,
delayed hatching, increased physical malformations, and a worse survival rate72,73. GLY was discovered by Lu et
al. to have an impact on zebrash body length shortening, improper hatching, and embryo death74. Zebrash
embryos exposed to GLY, on the other hand, showed cardiac anomalies such as ventricular dilatation, ventricular
wall thinning, and irregular rhythms74. A study by Pompermaier et al. indicated that exposure to GLY lowers the
survival rates of zebrash, causes hyperactivity and anti-anxiety behavior, aects larval anti-predation behavior
negatively, and raises acetylcholinesterase activity75. In zebrash larvae, Lanzarin et al. observed that GLY
triggers oxidative stress, inammation, and cell death76. Moreover, embryos exposed to high concentrations of
GLY showed lower heart rate and hatching rate, as well as increased mortality and number of abnormalities76.
On the other hand, exposure to amounts that do not result in teratogenic eects caused a dose-dependent drop
in heart rate without signicantly altering development77. Nonetheless, the larvae exposed to these quantities
did not exhibit any alterations in histology77. According to DíazMartín et al., zebrash embryos exposed to
GLY for a brief period of time may develop skeletal, craniofacial, and motor disorders78. Bridi et al. showed that
GLY shortens the zebrash larvae’s eye distance and decreases the adult zebrash’s walking distance, average
speed, and crossing line79. It was discovered by Roy et al. that GLY causes neurotoxicity in zebrash80. Research
by Flach et al. showed that GLY has an impact on the Xenopus laevis embryos’ development of the heart and
nervous system81. Bullfrogs (Lithobates catesbeiana) tadpoles’ metabolic processes and behavioral performance
are aected by GLY exposure, according to research done by Costa et al.82. Furthermore, research has shown that
GLY’s lethal and sublethal eects on non-target plants may contribute to the decline of biodiversity in natural
forest remnants submerged in agricultural settings83. All of these instances suggest that GLY has inltrated the
ecosystem and might stay there, potentially endangering the ecosystem’s stability and equilibrium.
In this work, we rst examined the association between urine GLY and mortality using representative large
sample prospective data. We have made some signicant new discoveries. First o, there is a strong link between
the urine GLY and all-cause mortality according to our research. Additionally, the Kaplan Meier curve supports
our ndings. People with high urine GLY have comparatively greater rates of all-cause and cardiovascular
mortality when compared to those with low urinary GLY. GLY has been shown to be harmful to the heart
in numerous investigations. According to a retrospective study, patients who are exposed to GLY poisoning
may have certain arrhythmia, such as I degree atrioventricular block, intraventricular conduction delay, and
prolonging of the QTc interval84. Case reports from recent years have shown demonstrated that ingesting GLY
can harm the cardiovascular system to varied degrees85–89. e majority of patients received gastric lavage,
norepinephrine and vasopressin infusion, intubation and mechanical breathing, and substantial intravenous
uid replacement, despite the fact that the quantity of GLY ingested varied. Per Calderon et al., prolonged
exposure to the GLY environment may have an impact on women’s development of cardiovascular disease90.
On a cardiac organoid model produced from human pluripotent stem cells, Sun et al. discovered that GLY had
developmental toxicity91. In the study by Maia et al., GLY can lead to atherosclerosis regardless of exposure
route and concentration92. However, Printemps et al. contend that Roundup ® A herbicide formulated with
GLY and adjuvants can induce severe cardiac toxicity by blocking the CaV1.2 channel, leading to worsening
cardiac contractility and arrhythmia, which cannot be attributed to GLY93. Lee et al. discovered that infusion of
isopropylamine (IPA) salt (IPAG) containing GLY can alter the hemodynamics of piglets and cause piglet death,
while GLY has no such imp act94. Maybe as a result of the active ingredient GLY’s interaction with other ingredients
in herbicide formulations, or maybe because of their increased cytotoxic activity. In order to determine the
true health concerns associated with occupational and environmental exposure, more formulation research is
necessary when creating herbicides based on GLY. Notably, this research shows for the rst time the unique
biological signicance of urinary GLY concentration in the low threshold range, meaning that a small increase
in urinary GLY concentration is signicantly positively correlated with the risk of cardiovascular mortality
when the concentration is below 0.38 ng/mL. is nding challenges the conventional toxicology’s linear “dose-
response” cognitive framework and raises the prospect of non-monotonic dose-response relationships or critical
threshold eects at very low exposure levels. Based on our research data and analysis process, urinary GLY
concentration is very likely to become a potential biomarker for cardiovascular mortality risk which may be
more signicant in the low concentration range, even though there are currently no epidemiological studies
reporting similar phenomena. e nding oers fresh concepts and avenues for investigation in the area of risk
assessment for cardiovascular disease. Further investigation into the inherent connection between variations in
low-level urine GLY concentration and the risk of cardiovascular mortality may be feasible in the future, thereby
providing more valuable information for the prevention and management of cardiovascular disease.
Several investigations have indicated that GLY may have carcinogenic properties. Dal’Bó et al. discovered
that while GLY can have a major cytotoxic eect on cells, it can also have a major proliferative eect, particularly
on papillary thyroid cancer cells95. An increased risk of breast cancer may be linked to exposure to aminomethyl
phosphonic acid (AMPA), the primary metabolite of GLY, according to a prospective study by Franke et al.96.
Herbicides based on GLY have been shown by Silva et al. to decrease autophagy and enhance energy metabolism
in C6 glioma cell lines97. Martínez et al. established that exposure to GLY in the environment is problematic by
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demonstrating how GLY and AMPA cause oxidative stress, development, and cell death in human neuroblastoma
cell line SH-SY5Y neurons via the pathways of necrosis, autophagy, and apoptosis98. Malatesta et al. showed that
hepatic cancer tissue culture (HTC) cells’ metabolic pathways can be disrupted by low doses of GLY99. C onversely,
Parajuli and colleagues showed that the combination of methoxyacetic acid (MAA) and AMPA can induce
apoptosis in prostate cancer cells, indicating its potential as a prostate cancer treatment medication100. e main
source of the debate on GLY’s carcinogenicity is an IARC assessment. GLY was categorized as a “possible human
carcinogen” (Class 2A) by the IARC in 2015. is classication is based on ndings from in vitro research,
animal trials, and epidemiological studies, some of which have linked GLY to non-Hodgkin’s lymphoma (NHL).
But it’s important to keep in mind that the IARC’s designation of GLY as “possibly carcinogenic” does not imply
that it causes cancer; rather, it suggests that there is enough evidence to support the possibility that it may cause
cancer, but the ndings are conicting or the evidence is insucient. e degree and mode of exposure must
also be taken into account when assessing GLY’s carcinogenic consequences. e amounts that people who are
directly exposed to GLY, such farmers, gardeners, and nearby residents, receive from GLY exposure or spraying
are signicantly higher than those that they consume through food. ese populations may therefore be at
greater risk for health problems. However, there isn’t any solid proof that GLY causes cancer directly, even in
these populations. It’s also important to note that GLY may be present in trace amounts in plants themselves.
is does not imply that all plants are GLY-contaminated; rather, it indicates that because GLY is so pervasive in
the environment, plants may absorb traces of the chemical while they are growing. Whether these small levels of
GLY are harmful to human health is still up for debate, though. e results of our research indicated that, even
aer controlling for confounding variables, there was a negative correlation between urine GLY content and
cancer mortality; however, this relationship was not statistically signicant. Furthermore, the protective eect
of GLY against cancer is not yet supported by any trustworthy scientic data. We consider that the incredibly
complicated inuencing factors of cancer mortality may be the cause of this outcome. Despite our best eorts to
account for known confounding variables, the results may still be imprecise due to unmeasured or insuciently
controlled confounding variables. To further conrm whether GLY has carcinogenic eects or its possible health
impacts, more carefully planned and sizable sample investigations are therefore still required in the future,
particularly long-term tracking and large-scale population research.
ere is mounting evidence that GLY may also harm dierent organs to diering degrees. According to a
recently released study, there is a positive linear link between non-alcoholic fatty liver disease (NAFLD) and GLY
exposure101. Another prospective study discovered that early exposure to GLY and AMPA during childhood
may raise the risk of metabolic diseases related to the liver and heart in early adulthood102. Tang et al. showed
that GLY signicantly harmed rats’ livers and resulted in an imbalance in the concentration of dierent mineral
elements in the rats’ various organs103. Liu et al. demonstrated that GLY can worsen liver toxicity by blocking
the Nrf2/GSH/GPX4 axis, which causes iron death in the liver cells104. e work of Gasnier et al. discovered
that GLY can harm liver cell lines intracellularly at various levels; however, human cell lines can be somewhat
shielded from this pollution by a combination of Dig1 medicinal plant extract105. Urine KIM-1 is the most
eective early biomarker for kidney injury, according to research by Wunnapuk et al. who also showed that GLY-
induced nephrotoxicity can occur106. Furthermore, GLY appears to have some eect on the neurological system.
Oliveira et al. reported that GLY has an age- and tissue-specic impact on the hypothalamus pituitary thyroid
axis107. Adewale et al. observed that in the brains of Wistar rats, GLY can trigger markers of oxidative stress,
inammation, and cell death108. Winstone et al. showed that GLY penetrates the brain, causes a dose-dependent
disruption of the transcriptome, and raises the expression of TNF α and soluble A β109. Cattani noticed that
GLY may cause extracellular glutamate levels to become too high, which would then cause oxidative stress and
glutamate excitotoxicity in the rat hippocampal tissues110. According to Gui et al., Parkinson’s disease may be
linked to exposure to commonly used GLY111. Numerous studies have oered sucient data to demonstrate the
possible risk of urinary GLY, despite the fact that there is still considerable debate and doubt about the connection
between this chemical and damage to human organs. us, given the possible health hazards associated with
GLY, we need to take proactive preventive actions, such as tightening laws governing the use of pesticides,
increasing public awareness of safety issues, lowering exposure outside of the workplace, and promoting the
adoption of greener substitutes. In order to lessen or even reverse the harm that GLY does to organs, people
that are already impacted by it must receive prompt medical monitoring and intervention. In summary, the
application of GLY needs to be prudent and careful in order to protect human health and safety while preserving
agricultural output eciency. To strengthen the scientic foundation for protecting human health, additional
comprehensive and long-term studies are required in the future to elucidate the precise mechanism and extent
of urinary GLY’s impact on organ damage.
It’s crucial to keep in mind that GLY has also been linked to some degree of reproductive system impairment.
According to Chianese et al., GLY can activate estrogen receptors and cause cell death in prostate cells. It also
functions as a heteroestrogen. Hormonal changes that follow could reduce fertility112. Lu et al. discovered
that GLY, which may be harmful to reproduction, stimulates iron death and suppresses testosterone synthesis
via ferritin autophagy mediated by NCOA4113. Long-term dietary exposure to GLY in chickens has been
demonstrated by Estienne et al. to cause the accumulation of GLY in egg yolks, which causes severe early
embryo mortality and delayed embryo development in survivors114. ese negative eects go away aer two
weeks of GLY exposure114. Ganesan et al. revealed that ovarian mitochondria and oxidative stress proteins are
changed in female C57BL6 mice exposed to GLY115,116. Cai et al. determined that even very low concentrations
(0.9 ppm) of GLY are detrimental to pre-implantation development in cattle [117]. ey also reported that
exposure to agricultural recommended dosages of GLY can result in stunted in vitro growth and fast loss of
bovine embryos117. Additionally, Cavalli et colleagues demonstrated that GLY may aect male fertility118. GLY
has been shown by Razi et al. to impact spermatogenesis, motility of sperm, and anomalies in rat testicular tissue,
all of which may result in infertility119. Benachour et al. reported that in human umbilical cord, embryonic,
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and placental cells, GLY causes necrosis and apoptosis120. Dallegrave and colleagues found that GLY causes
embryonic bone development to be delayed and is hazardous to the mother of Wistar rats121. In conclusion,
it is impossible to overlook the possible harm that GLY could cause to the developing reproductive system.
Numerous studies have alerted us to the danger, even though there is still some debate on its precise impact. It
is additionally essential to keep in consideration that the majority of GLY research is based on animal studies,
and that the dosage of GLY in animal studies may dier signicantly from the amounts of exposure in humans.
is necessitates analyzing research ndings with caution and a scientic mindset. To investigate the possible
toxicity of GLY under high exposure, animal tests are usually carried out in harsh environments. e results of
animal trials cannot be directly applicable to humans because these concentrations are frequently far greater
than the amounts that people may encounter in their daily lives. Additionally, GLY exposure in humans typically
occurs through a variety of pathways, including the food chain, air, and water, whereas in animals, trials are
typically carried out in highly controlled situations and the sources of GLY that animals come into contact with
are single and obvious. It is challenging to determine the precise amount of GLY that humans are exposed to due
to the intricacy of these exposure pathways. erefore, in order to have a more thorough picture of the actual
state of human exposure to GLY, we must rely on epidemiological studies and environmental monitoring data.
Moreover, species dierences may also play a role. Dierent animal species may react, tolerate, and metabolize
GLY quite dierently than humans do. Certain animals may have a high resistance to GLY and will not react
similarly to people, even at high doses, while other animals may be more sensitive to the chemical and need
higher doses to have eects comparable to those seen in humans. erefore, the amount and concentration of
GLY in animal studies cannot be directly compared to human exposure. us, we should completely take into
account variables like exposure pathways, dosages, length, and individual characteristics when describing the
distinctions between exposure in humans and animal study. In order to more precisely evaluate the possible
eects of GLY on human health, we need also keep an eye out for fresh research ndings. In conclusion, even
though the dosages used in animal tests and human exposure dier, these studies nevertheless give us important
insights into how to use GLY more safely and shield people from any potential risks.
Secondly, we note that sex and hypertension may aect the relationship between urinary GLY and mortality.
In subgroup analysis of sex, we observed that female individuals had lower rates of all-cause mortality. It is true
that there is a correlation between gender and mortality, but this correlation is highly complex and inuenced by
a variety of factors, such as work, environment, behavior and lifestyle, and heredity. Furthermore, we observed
that the fraction of low concentration urine GLY in females is larger than in males, which could be one of
the causes of the lower all-cause death rate in females (Table1). Additionally, GLY may have a higher eect
on cancer mortality in patients without hypertension, according to our subgroup study. We speculate that it
might be because the toxic eects of GLY are more likely to appear in non-hypertensive patients with relatively
simple health status, whereas the numerous illness loads and medication interference of hypertensive patients
may obscure the impact of GLY. It is important to remember that these conclusions are merely theories, and
additional clinical data will be needed to validate our research ndings. As of yet, there is no known cure for
GLY poisoning, and the only available treatment is prompt systemic support. More research could lead to the
development of GLY inhibitors that are more potent in the future. However, the primary way to solve the issue
is to stop the misuse of herbicides like GLY. erefore, we should strengthen policy supervision and regulatory
enforcement, strictly formulate and implement usage norms, enhance agricultural technology guidance and
training, and raise public environmental awareness, in order to bring the minimum negative impact while
maximizing the benets of GLY.
We must recognize that this study has signicant drawbacks even though it is a huge sample size and
thoroughly illustrates the intricate stratied sampling methodology of NHANES. First o, despite our best
eorts to account for confounding variables, lifestyle, medication, occupational characteristics, and other factors
that may be known or unmeasured confounding factors cannot be completely ruled out as potential sources of
bias in the research ndings. In addition, there may be complex interactions between confounding variables
and between confounding variables and research factors, which can make the impact of confounding factors
more complex. ere may be a synergistic eect between GLY exposure and lifestyle factors such as smoking
and alcohol consumption, which collectively aect human health. However, it is dicult to accurately separate
and eectively control the eects of this interaction separately in statistical analysis. Moreover, in studying the
eects of long-term GLY exposure on human health, confounding variables such as dietary habits and living
environment of research subjects may change during the study period. For instance, an individual’s water
intake can have a big impact on how diluted their urine is, which can change the target substance’s detection
concentration. e accuracy of detection results may be hampered by diets that contain compounds that
physically resemble urine GLY or that alter the body’s metabolism of GLY. Furthermore, statistical analysis can
oen only be controlled based on data from a specic time point or limited time period, making it dicult to
consider these dynamic changes in a real-time and comprehensive manner. Second, the majority of our ndings
are derived from questionnaire surveys, and self-reporting by participants could contain bias. It is noteworthy,
however, that questionnaire surveys constitute a signicant part of the National Health and Nutrition Survey,
and that a great deal of research has been done using the data from these surveys. irdly, results should not be
extended to other nations or age groups because the population we covered consisted of adult Americans who
are 18 years of age or older. In conclusion, before the aforementioned results are applied in clinical settings, more
clinical research is required to conrm these results.
Conclusion
Overall, this study investigated the relationship between urinary GLY and mortality, and discovered that there
might be an association between urinary GLY and all-cause mortality, which we observed that this correlation is
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more pronounced in female populations. Furthermore, urine GLY may have a higher eect on cancer mortality
in people without hypertension.
Data availability
e original contributions presented in the study are included in the article, further inquiries can be directed to
the corresponding author.
Received: 31 October 2024; Accepted: 19 March 2025
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Acknowledgements
We would like to give special thanks to the supporters, workers and participants of NHANES for their contribu-
tion to the completion of this study.
Author contributions
YC and ZW conceived and designed the study; YC draed the manuscript and participated in the literature
search, data analysis, and interpretation. ZW collected the data and contributed to the statistical analysis. All
authors contributed to the review/editing of key intellectual content of the manuscript. ML and YW provided
key revisions. All authors contributed to the article and approved the submitted version.
Funding
is work was supported by the National Natural Science Foundation of China (81660085) and the Key Science
and Technology Innovation Projects of Jiangxi Provincial Health Commission (2024ZD007).
Declarations
Competing interests
e authors declare no competing interests.
Ethical approval
e studies involving human participants were reviewed and approved by Ethics Review Committee of the
National Center for Health Statistics. e patients/participants provided their written informed consent to
participate in this study.
Additional information
Supplementary Information e online version contains supplementary material available at h t t p s : / / d o i . o r g / 1
0 . 1 0 3 8 / s 4 1 5 9 8 - 0 2 5 - 9 5 1 3 9 - y .
Correspondence and requests for materials should be addressed to M.L. or Y.W.
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