Table S1. Serch strategy for retrieving literature on the association between metabolic syndrome and PFAS in each databases

Search Strings#1 Substance terms

Perfluoroalkyl* substance*) OR polyfluoroalkyl* substance* OR per*fluorinated alkyl* substance*) OR poly*fluorinated alkyl* substance*) OR perfluorooctane sulfon*) OR perfluorooctane*) OR perfluorooctan*) OR perfluorooctanic*) OR perfluoroctanoic*) OR polyfluoroalkyl*) OR polyfluorinated*) OR perfluoroalkyl*) OR Perfluorinated*) OR perfluorobutanoic*) OR perfluorohexanoic*) OR perfluorohexane) OR) OR perfluorononanoic*) OR perfluorononan*) OR perfluoro*) OR polyfluoro*) OR Fluorocarbons) OR perfluorooctanyl*) OR *fluorinated) OR PF?A) OR PF?S

#2 outcome terms

Metabolic syndrome) OR syndrome X) OR metabolic disorder*) OR MetS) OR MetSyn) OR metabolic disease*) OR metabolic abnormalitie*) OR metabolic *function) OR metabolic disturbance*) OR Cardiometabolic*) OR Insulin resistance syndrome

#3 hypertension OR high blood pressure#4 hyperlipidemia OR lipid disorder OR dyslipidemia #5 high blood sugar OR diabetes mellitus OR Diabetes OR impaired glucose tolerance OR Insulin resistance OR

Hyperinsulinemia#6 abdominal obesity OR Obesity OR waist circumference#7 #3 AND #4#8 #3 AND #5#9 #3 AND #6#10 #4 AND #6#11 #4 AND #5#12 #5 AND #6#13 #2 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12

#14 #13 AND #1#15 Human study terms

epidemio* OR Cohort OR population* OR participant* OR exposure* OR questionnaire* OR case?control OR cross?sectional OR Human

#16 #14 AND #15

Newcastle-Ottawa Scale adapted for cross-sectional studiesSelection: (Maximum 5 stars)1) Representativeness of the sample:

a) Truly representative of the average in the target population. * (all subjects or random sampling)b) Somewhat representative of the average in the target population. * (non-random sampling)c) Selected group of users.d) No description of the sampling strategy.

2) Sample size: a) Justified and satisfactory. * b) Not justified.3) Non-respondents: a) Comparability between respondents and non-respondents characteristics is established, and the response rate is satisfactory. * b) The response rate is unsatisfactory, or the comparability between respondents and non-respondents is unsatisfactory. c) No description of the response rate or the characteristics of the responders and the non-responders.4) Ascertainment of the exposure (risk factor): a) Validated measurement tool. ** b) Non-validated measurement tool, but the tool is available or described.* c) No description of the measurement tool.Comparability: (Maximum 2 stars)1) The subjects in different outcome groups are comparable, based on the study design or analysis. Confounding factors are controlled. a) The study controls for the most important factor (select one). * b) The study control for any additional factor. *Outcome: (Maximum 3 stars)1) Assessment of the outcome: a) Independent blind assessment. ** b) Record linkage. ** c) Self report. * d) No description.2) Statistical test: a) The statistical test used to analyze the data is clearly described and appropriate, and the measurement of the association is presented, including confidence intervals and the probability level (p value). * b) The statistical test is not appropriate, not described or incomplete.

This scale has been adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort studies to perform a quality assessment of cross-sectional studies for the systematic review, “Are Healthcare Workers’ Intentions to Vaccinate Related to their Knowledge, Beliefs and Attitudes? A Systematic Review”.We have not selected one factor that is the most important for comparability, because the variables are not the same in each study. Thus, the principal factor should be identified for each study.In our scale, we have specifically assigned one star for self-reported outcomes, because our study measures the intention to vaccinate. Two stars are given to the studies that assess the outcome with independent blind observers or with vaccination records, because these methods measure the practice of vaccination, which is the result of true intention.

Table S2. Quality assessment of included studies.

Representativeness of the sample

Sample size

Non-respondents

Ascertainment of the exposure (risk factor)

controls for most important factors

control for any additional

factor

Assessment of the outcome Statistical test Total

Lin et al. 2009 * * - ** * * ** * 9

Fisher et al. 2013 * * * ** * * ** * 10

Yang et al. 2018 - - - ** * - ** * 6

Liu et al. 2018 * * - ** * * ** * 9

Leary et al. 2018 * * - ** * - ** * 8

Christensenet al. 2019 * * - ** * * ** * 9

Chen et al. 2019 * - - ** * * ** * 8

Te-Wei Lin et al. 2020 * * * ** * * ** * 10

Wan- Lin Ye et al. 2020 * * - ** * * ** * 9

Zare Jeddi et al. 2021 * * * ** * * * * 10

Occupational exposure

Olsen et al. 2007 * * 0 ** * 0 ** * 8

Leary et al. 2019 * - - ** * - ** * 7

Table S3. Definition of metabolic syndrome

NCEP ATP III (2005) WHO (1998) EGIR (1999) IDF (2005) AACE (2003) Joint statement of IDF, NHLBI, IAS, IASQ and AHA (Alberti and others 2009)

Absolutely required

None Diabetes or impaired glucose tolerance or Insulin resistance (IR)

Hyperinsulinemia (plasma insulin >75th percentile) only non-diabetics subjects

Central obesity (waist circumference): ≥94cm (M), ≥80 CM (F)

impaired fasting glucose or IGT: impaired glucose tolerance

None

Criteria Any three of five criteria below

Insulin resistance or diabetes, plus two of criteria below

Hyperinsulinemia, plus two or more of the four criteria below

Obesity, plus two of the four criteria below

Plus any of the following based on clinical judgment

Any three of five criteria below

Obesity Waist circumference: >102 cm(M), >88 cm (F)

Waist/hip ratio: >0.90 (M), >0.85 (F); or BMI ≥30 kg/m2

Waist circumference: ≥94 cm (M), ≥80cm (F)

Central obesity already required

BMI ≥25 kg/m2 Waist circumference: >102 cm(M), >88 cm (F)

Hyperglycemia Fasting glucose ≥100 mg/dl (includes diabetes) or Rx

Insulin resistance or IGT, IFG already required (includes diabetes)

Insulin resistance already required; Fasting glucose ≥110 mg/dl

Fasting glucose ≥100 mg/dl or previouslly diagnosed diabetes

IGT or IFG (but not diabetes)

Fasting glucose ≥100 mg/dl or Rx

Dyslipidemia (lipoprotein level) Elevated TG

TG≥ 150 mg/dl or Rx TG≥ 150 mg/dl TG≥ 177 mg/dl TG≥ 150 mg/dl or Rx TG≥ 150 mg/dl TG≥ 150 mg/dl or Rx

Dyslipidemia (second, separate criteria) Reduced HDL- cholesterol

HDL-C:<40 mg/l (M); <50 mg/l (F) or Rx

HDL-C: <35 mg/dl (M); <39 mg/dl (F)

HDL-C: <35 mg/dl (M); <39 mg/dl (F)

HDL- cholesterol: <40 mg/l (M); <50 mg/l (F) Rx

Low HDL- cholesterol: <40 mg/l (M); <50 mg/l (F)

HDL cholesterol:<40 mg/l (M); <50 mg/l (F) or Rx

HypertensionElevated BP (mmHg)

≥130 mmHg systolic and/or ≥85 mmHg diastolic or Rx

≥140 mmHg systolic and/or 90 mmHg diastolic or Rx

≥140 mmHg systolic and/or 90 mmHg diastolic or Rx

≥130 mmHg systolic and/or ≥85 mmHg diastolic Rx

≥130 mmHg systolic and/or ≥85 mmHg diastolic or Rx

≥130 mmHg systolic and/or ≥85 mmHg diastolic or Rx

Other criteria MicroalbuminuriaUrinary albumin: creatinine ratio of >30mg/g.

Family history of type 2 diabetes, hypertension, or CVD, Polycystic ovary syndrome, Sedentary lifestyle, Advancing age,

*BP, blood pressure; FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol; TG, triglycerideRx: receiving treatment; National Cholesterol Education Program’s (NCEP) Adult Treatment Panel III,European Group for the study of Insulin Resistance (EGIR),The American Association of Clinical Endocrinologists (AACE),the International Diabetes Federation (IDF)

CD

A B

Figure S1. Random effects meta-analysis of the effects of PFAS on metabolic syndrome (pooled OR value with corresponding 95% CI) including study by Leary 2018. A. Correlation between PFOS and metabolic syndrome. B.Correlation between PFOA and metabolic syndrome. C. Correlation between PFHxS and metabolic syndrome. D. Correlation between PFNA and metabolic syndrome.

A B

C D

Figure S2. Fixed effects meta-analysis of the effects of PFAS on metabolic syndrome (pooled OR value with corresponding 95% CI). A. Correlation between PFOS and metabolic syndrome. B.Correlation between PFOA and metabolic syndrome. C. Correlation between PFHxS and metabolic syndrome. D. Correlation between PFNA and metabolic syndrome.