Application of BRAFO-Tiered Approach for Risk–Benefit Assessment of Nut Consumption in Chinese Adults
Abstract
1. Introduction
2. Material and Methods
2.1. Concentration Data of AFs in Nuts
2.2. Nut Consumption Data
2.3. Risk–Benefit Assessment
2.3.1. Pre-Assessment and Question Formulation
2.3.2. Tier 1
2.3.3. Tier 2
2.3.4. Tier 3
Estimation of Dietary Exposure to Total AFs from Nuts in Chinese Adults
Dose–Response Relationship
Calculation of DALY
2.4. Statistical Analyses
3. Result
3.1. Tier 1: Independent Assessment of the Beneficial and Harmful Health Effects of Nut Consumption
3.1.1. The Beneficial Effects of Nut Consumption
3.1.2. Risks Associated with Nut Consumption
3.2. Tier 2: Qualitative Assessment of the Risks and Benefits Associated with Nut Consumption
3.3. Tier 3 and Tier 4
3.3.1. Dose–Response Relationship
3.3.2. DALY
3.4. Uncertainty Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Abbreviation | Definition |
AF | Aflatoxin |
AFB1 | Aflatoxin B1 |
AFB2 | Aflatoxin B2 |
AFG1 | Aflatoxin G1 |
AFG2 | Aflatoxin G2 |
BMDL10 | Benchmark Dose Lower Confidence Limit 10% |
BMI | Body Mass Index |
BRAFO | Benefit–Risk Analysis for Foods |
CAD | Coronary Artery Disease |
CHD | Coronary Heart Disease |
CI | Confidence Interval |
CVD | Cardiovascular Diseases |
DALY | Disability-Adjusted Life Year |
DASH | Dietary Approaches to Stop Hypertension |
ELISA | Enzyme-Linked Immunosorbent Assay |
GBD | Global Burden of Disease |
HBV | Hepatitis B Virus |
HCC | Hepatocellular Carcinoma |
HDL | High-Density Lipoprotein |
HPLC | High-Performance Liquid Chromatography |
IARC | International Agency for Research on Cancer |
IHD | Ischemic Heart Disease |
LOD | Limits of Detection |
MI | Myocardial Infarction |
MOE | Margin of Exposure |
NOS | Newcastle–Ottawa Scale |
OR | Odds Ratio |
PHC | Primary Health Care |
RBA | Risk–Benefit Assessment |
RCS | Restricted Cubic Spline |
RR | Relative Risk |
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Nuts | Number | Positive Samples (%) | Mean (μg/kg) | P95 (μg/kg) | Max (μg/kg) | |||
---|---|---|---|---|---|---|---|---|
LB a | UB a | LB a | UB a | LB a | UB a | |||
Ginkgo nut | 19 | 4 (21.05) | 0.31 | 0.67 | 1.32 | 1.41 | 4.00 | 4.00 |
Walnut | 171 | 14 (8.19) | 0.12 | 0.51 | 0.12 | 0.52 | 6.70 | 7.10 |
Chestnut | 9 | 0 (0.00) | 0.00 | 0.40 | 0.00 | 0.40 | 0.00 | 0.40 |
Pine nut | 206 | 25 (10.68) | 0.41 | 0.78 | 1.38 | 1.43 | 41.02 | 41.12 |
Almond | 413 | 54 (13.08) | 0.20 | 0.58 | 1.00 | 1.26 | 11.20 | 11.50 |
Cashew | 62 | 5 (8.06) | 0.10 | 0.49 | 0.93 | 1.22 | 1.94 | 2.24 |
Hazelnut | 38 | 1 (2.63) | 0.03 | 0.42 | 0.00 | 0.40 | 0.98 | 1.08 |
Pistachio | 490 | 56 (11.43) | 0.16 | 0.54 | 0.81 | 1.04 | 18.00 | 18.25 |
Peanut | 91 | 5 (5.49) | 0.16 | 0.54 | 0.40 | 0.75 | 6.90 | 7.20 |
Sunflower seed | 896 | 102 (11.38) | 1.05 | 1.44 | 2.00 | 2.30 | 82.37 | 82.42 |
Pumpkin seed | 357 | 37 (10.36) | 0.28 | 0.66 | 0.84 | 1.12 | 31.00 | 31.10 |
Watermelon seed | 419 | 38 (9.07) | 0.10 | 0.48 | 0.69 | 0.99 | 3.96 | 4.21 |
Amygdalus communis L. | 92 | 6 (6.52) | 0.22 | 0.61 | 0.50 | 0.78 | 9.79 | 9.84 |
Macadamia nut | 16 | 2 (12.50) | 0.21 | 0.57 | 1.66 | 1.68 | 1.83 | 1.93 |
Pecan | 48 | 0 (0.00) | 0.00 | 0.40 | 0.00 | 0.40 | 0.00 | 0.40 |
Other b | 22 | 2 (9.09) | 0.19 | 0.57 | 0.08 | 0.48 | 4.00 | 4.00 |
Total | 3349 | 348 (10.39) | 0.42 | 0.80 | 0.99 | 1.21 | 82.37 | 82.42 |
Author, Year | Average Follow-Up Time (Year) | Country | Outcome | Sample Size (Cases) | Dose | RR | NOS | Adjustment Factor |
---|---|---|---|---|---|---|---|---|
Fraser et al. (1992) [37] | 5 | USA | Fatal CHD | 31,208 (260) | <1 serving/week | 1 | 7 | Age, sex, smoking, exercise, relative weight, high blood pressure and all food variables. |
1–4 servings/week | 0.76 (0.56, 1.04) | |||||||
≥5 servings/week | 0.52 (0.36, 0.76) | |||||||
Nonfatal MI | 31,208 (134) | <1 serving/week | 1 | |||||
1–4 servings/week | 0.78 (0.51, 1.18) | |||||||
≥5 servings/week | 0.49 (0.28, 0.85) | |||||||
Albert et al. (2002) [38] | 17 | USA | Nonfatal MI | 22,071 (1037) | 1 serving/month | 1 | 7 | Age (continuous), aspirin and beta carotene treatment assignment, evidence of cardiovascular disease before 12-month questionnaire, BMI, smoking, history of diabetes, history of hypertension, history of hypercholesterolemia, alcohol consumption, vigorous exercise, vitamin E, vitamin G and multivitamin use at baseline. |
1–3 servings/month | 1.22 (1, 1.51) | |||||||
1 serving/week | 1.20 (0.96, 1.50) | |||||||
≥2 servings/week | 1.04 (0.82, 1.33) | |||||||
Haring et al. (2014) [39] | 22 | USA | CHD | 12,066 (1147) | 0 serving/day | 1 | 8 | Age, sex, race, study center, total energy intake, smoking, education, systolic blood pressure, use of antihypertensive medication, HDLc total cholesterol, use of lipid-lowering medication, body mass index, waist-to-hip ratio, alcohol intake, sports-related physical activity, leisure-related physical activity, carbohydrate intake, fiber intake, and magnesium intake. |
0.1 serving/day | 0.89 (0.75, 1.06) | |||||||
0.2 serving/day | 0.86 (0.71, 1.05) | |||||||
0.4 serving/day | 0.83 (0.68, 1.01) | |||||||
1.0 serving/day | 0.91 (0.74, 1.12) | |||||||
Guasch-Ferré et al. (2017) [40] | 32 | USA | MI | 76,364 (3552) | 0 g/day | 1 | 7 | Age, Caucasian, BMI, physical activity, smoking status, physical examination for screening purposes, current multivitamin use, current aspirin use, family history of diabetes mellitus, myocardial infarction or cancer, history of diabetes mellitus, hypertension or hypercholesterolemia, intake of total energy, alcohol, red or processed meat, fruits and vegetables, and, in women, menopausal status and hormone use. In the NHS II study, the multivariable model was further adjusted for oral contraceptive use. |
1.68 g/day | 0.84 (0.76, 0.91) | |||||||
3.92 g/day | 0.76 (0.68, 0.86) | |||||||
9.24 g/day | 0.73 (0.64, 0.82) | |||||||
27 g/day | 0.69 (0.56, 0.83) | |||||||
92,946 (670) | 0 g/day | 1 | ||||||
1.47 g/day | 0.93 (0.77, 1.13) | |||||||
3.92 g/day | 0.79 (0.61, 1.02) | |||||||
7.98 g/day | 0.84 (0.63, 1.12) | |||||||
23.03 g/day | 0.57 (0.27, 1.23) | |||||||
41,526 (4168) | 0 g/day | 1 | ||||||
1.96 g/day | 0.93 (0.84, 1.03) | |||||||
3.92 g/day | 0.90 (0.81, 0.99) | |||||||
7.84 g/day | 0.88 (0.79, 0.97) | |||||||
24.08 g/day | 0.86 (0.76, 0.98) | |||||||
Larsson et al. (2018) [41] | 17 | Sweden | MI | 61,364 (4983) | 0 | 1 | 8 | Education, family history of myocardial infarction before 60 years of age, smoking, walking/bicycling, exercise, aspirin use and consumption of alcohol, fruits, vegetables and total energy, potential intermediates of the nut-CVD relationship, including body mass index, history of diabetes, history of hypertension and history of hypercholesterolemia. |
1–3 servings/month | 0.98 (0.92, 1.04) | |||||||
1 serving/week | 0.91 (0.79, 1.05) | |||||||
≥3 servings/week | 0.88 (0.70, 1.11) | |||||||
Perez-Cornago et al. (2020) [42] | 12.6 | Multinational | 490,311 (8504) | 0 | 1 | 7 | Age, smoking status and number of cigarettes per day, histories of diabetes, hypertension and hyperlipidemia, including Cambridge physical activity index, employment status, level of education completed, current consumption, BMI, and observed intakes of total energy, red and processed meat, and cheese are considered in the analysis. | |
0.006–0.5 g/day | 0.99 (0.90, 1.08) | |||||||
0.5–2.0 g/day | 0.97 (0.91, 1.04) | |||||||
2.0–5.3 g/day | 0.96 (0.89, 1.03) | |||||||
>5.3 g/day | 0.93 (0.86, 1.01) | |||||||
de Souza et al. (2020) [43] | 9.5 | Multinational | MI | 124,329 (2559) | <30 g/month | 1 | 8 | Age, sex, location, and center, follow-up time, lifestyle factors such as education, tobacco use, BMI, waist-to-hip ratio, physical activity, family history of CVD, diabetes, and cancer, and diet factors including fish, fruits, vegetables, red/processed meat, legumes, and total energy. |
30 g/month–30 g/week | 0.97 (0.85, 1.12) | |||||||
30 g/week–120 g/week | 0.99 (0.87, 1.13) | |||||||
≥120 g/week | 0.86 (0.72, 1.04) | |||||||
Ivey et al. (2021) [44] | 3.5 | USA | CAD | 179,827 (9908) | <1 serving/month | 1 | 7 | Age, sex, race, BMI, smoking status, alcohol intake, physical activity, education, modified DASH score. |
1–3 servings/month | 0.93 (0.89, 0.99) | |||||||
1 servings/week | 0.89 (0.84, 0.95) | |||||||
2–4 servings/week | 0.83 (0.78, 0.89) | |||||||
≥5 servings/week | 0.78 (0.72, 0.84) | |||||||
Mohammadifard et al. (2021) [45] | 11.25 | Iran | IHD | 5432 (594) | 0.64 g/day | 1 | 7 | Age, sex, education, residence area, smoking status, daily physical activity, family history of CVD, diabetes mellitus, hypertension, hypercholesterolemia and aspirin use, and menopausal status in female, BMI and dietary factors. |
0.66 g/day | 1.07 (0.84, 1.37) | |||||||
0.96 g/day | 1.01 (0.79, 1.28) | |||||||
2.28 g/day | 0.98 (0.76, 1.27) | |||||||
Ikehara et al. (2021) [46] | 14.8 | Japan | IHD | 74,793 (849) | 0 g/day | 1 | 7 | Age, sex, PHC, smoking status, alcohol consumption, perceived stress level, physical activity, and vegetable, fruit, fish, soy, sodium, and total energy intakes, BMI, history of hypertension, history of diabetes, and cholesterol-lowering drug. |
0.7 g/day | 0.98 (0.79, 1.21) | |||||||
1.3 g/day | 0.93 (0.77, 1.11) | |||||||
4.3 g/day | 0.97 (0.80, 1.17) | |||||||
Author, Year | Country | Research Year | Study Design | Matching Factors | Biomarker | Dose | Case | Control | OR | NOS | Adjustment Factor |
---|---|---|---|---|---|---|---|---|---|---|---|
Yu MW et al. (1997) [47] | China, Taiwan | 1988–1992 | Individually matched | Age, interview, urine collection time. | urinary AFM1 (ng/mL) | <1.61 | 9 | 18 | 1 | 7 | Educational level, ethnicity, habitual alcohol drinking, and cigarette smoking status. |
1.61–2.85 | 10 | 10 | 1.9 (0.5, 7.2) | ||||||||
>2.85 | 23 | 15 | 6 (1.2, 29) | ||||||||
Long XD et al. (2005) [48] | GuangXi | - | Frequency matched | Age, sex, ethnicity. | AFB1 (μg/day) | >7 | 536 | 447 | 1 | 4 | - |
<7 | 140 | 71 | 5.82 (3.26, 10.38) | ||||||||
Long XD et al (2006) [49] | GuangXi | 2004–2005 | Individually matched | Age, sex, ethnicity, and hepatitis B virus infection. | AFB1 (μg/day) | >7 | 58 | 127 | 1 | 6 | Adjusted for age, sex, ethnicity, HBV infection, anti-HCV, and AFB1 exposure levels. |
<7 | 175 | 130 | 5.55 (3.82, 8.06) | ||||||||
YU SZ et al. (2008) [50] | TaiXing | 2000 | Frequency matched | Age, length of residence. | AFB1 albumin adduct (fmol/mg) | <247 | 33 | 94 | 1 | 8 | Age, gender, BMI, education, alcohol consumption, smoking, virus infection. |
247.1–388.9 | 46 | 94 | 1.15 (0.61, 2.14) | ||||||||
388.9–545 | 42 | 95 | 1.19 (0.61, 2.21) | ||||||||
>545.1 | 61 | 94 | 1.63 (0.9, 2.96) | ||||||||
Wu HC et al. (2009) [51] | China, Taiwan | 1990–2004 | Frequency matched | Age, gender, residential township, recruitment date. | AFB1-albumin adducts (fmol/mg) | <26.9 | 66 | 263 | 1 | 8 | Aflatoxin biomarker assay batch, HBsAg, anti-HCV status, habitual smoking, alcohol consumption, and BMI. |
26.9–43.5 | 58 | 262 | 1.11 (0.69, 1.83) | ||||||||
43.5–71.35 | 49 | 264 | 1.18 (0.69, 2.03) | ||||||||
>71.35 | 57 | 263 | 1.47 (0.83, 2.58) | ||||||||
Yao JG et al. (2014) [52] | GuangXi | 2004–2012 | Individually matched | Age, ethnicity, sex, HBV and HCV infection. | AFB1-albumin adducts (ln fmol/mg) | <2.18 | 352 | 1060 | 1 | 7 | - |
2.18–2.98 | 417 | 604 | 2.08 (1.75, 2.47) | ||||||||
>2.98 | 717 | 332 | 6.52 (5.46, 7.79) | ||||||||
Zheng CF et al. (2017) [53] | ChongQing | 2013–2016 | Individually matched | Age, gender. | AFB1-albumin adducts (ng/g) | <133.1 | 81 | 132 | 1 | 7 | Smoking, drinking alcohol, HBV infection, family history of HBV infection, family history of tumors, diabetes, and hyperglycemia. |
≥133.1 | 133 | 82 | 1.9 (1.1, 3.4) | ||||||||
Chu YJ et al. (2018) [54] | China, Taiwan | 1991–2011 | Individually matched | Age, gender, residence, date of blood sample collection. | AFB1-albumin adducts (fmol/mg) | <21.5 | 23 | 1475 | 1 | 9 | Age, sex, education level, smoking status, drinking status, HBsAg status. |
>21.5 | 21 | 468 | 2.43 (1.31, 4.52) | ||||||||
Health Impact Endpoint | Incidence of Health Effects | Severity of Health Effects [72] | Effect Duration | Age-Standardized DALY (1/105) [69] | Age-Standardized Mortality (1/105) (95% CI) | Changes in Health Effects |
---|---|---|---|---|---|---|
Coronary heart disease | Decrease | 0.790 | Lifelong after illness | 2132.1 (2093.7, 2179.8) a | 108.7 (99.8, 115.6) a [70] | Beneficial |
Liver cancer | Increase | 0.857 | Lifelong after illness | 253.6 (243.2, 266.2) | 10.2 (9.8, 10.7) [71] | Adverse |
Subgroup | N Studies | OR (95% CI) | p for Group Differences |
---|---|---|---|
Region | 0.076 | ||
Europe | 1 | 0.88(0.70, 1.1) | |
USA | 8 | 0.74 (0.62, 0.87) | |
Asia | 2 | 0.97 (0.84, 1.13) | |
Multinational | 2 | 0.92 (0.85, 0.99) | |
Follow-up time | 0.18 | ||
<10 years | 4 | 0.77 (0.69, 0.86) | |
≥10 years | 9 | 0.82 (0.76, 0.90) | |
Adjusted for hypertension | 0.72 | ||
NO | 3 | 0.82 (0.75, 0.90) | |
YES | 10 | 0.79 (0.68, 0.92) | |
Overall | 13 | 0.81 (072, 0.91) |
Scenarios c | Man | Woman | ||||
---|---|---|---|---|---|---|
CHD | Liver Cancer | ΔDALY | CHD | Liver Cancer | ΔDALY | |
sunflower seeds a | ||||||
reference scenario | 810.08 (802.71, 818.68) | 801.04 (797.97, 803.97) | 452.47 (448.56, 456.32) | 269.82 (268.77, 271.15) | ||
alternative scenario 1 | 703.34 (697.08, 710.90) | 803.39 (800.37, 806.25) | −104.39 (−105.51, −103.24) | 392.73 (389.22, 398.04) | 270.08 (269.03, 271.41) | −58.79 (−59.33, −58.38) |
alternative scenario 2 | 661.33 (655.44, 668.45) | 806.16 (803.07, 809.17) | −143.63 (−145.17, −142.03) | 369.12 (365.78, 372.24) | 270.26 (269.30, 271.69) | −81.29 (−82.00, −80.65) |
alternative scenario 3 | 620.45 (614.92, 627.15) | 809.20 (806.00, 811.93) | −181.47 (−183.80, −179.64) | 346.23 (234.09, 349.16) | 270.64 (269.59, 271.98) | −102.94 (−103.83, −102.17) |
pecans b | ||||||
reference scenario | 810.08 (802.71, 818.68) | 801.04 (797.97, 803.97) | 452.47 (448.56, 456.32) | 269.82 (268.77, 268.77) | ||
alternative scenario 1 | 703.34 (697.08, 710.90) | 801.70 (798.63, 804.63) | −106.08 (−107.26, −104.89) | 392.73 (389.22, 398.04) | 270.76 (269.70, 272.12) | −59.47 (−60.03, −59.03) |
alternative scenario 2 | 661.33 (655.44, 668.45) | 802.39 (799.32, 805.33) | −147.40 (−149.05, −145.77) | 369.12 (365.78, 372.24) | 271.88 (270.89, 273.16) | −82.81 (−83.59, −82.19) |
alternative scenario 3 | 620.45 (614.92, 627.15) | 803.11 (800.04, 806.05) | −187.56 (−189.65, −185.56) | 346.23 (234.09, 349.16) | 273.11 (272.06, 274.49) | −105.41 (−106.38, −104.62) |
Scenarios a | Descriptive Level | MOE b of AFB1 | MOE b of Total AFs | ||
---|---|---|---|---|---|
LB | UB | LB | UB | ||
Reference scenario | |||||
p50 | N/A c | N/A c | N/A c | N/A c | |
p75 | N/A c | N/A c | N/A c | N/A c | |
p90 | 15,751 d | 5648 | 3900 | 2035 | |
mean | 50,553 d | 18,127 d | 12,519 d | 6532 | |
Alternative scenario 1 | |||||
p50 | 23,108 d | 8286 | 5722 | 2986 | |
p75 | 20,027 d | 7181 | 4959 | 2588 | |
p90 | 15,020 d | 5386 | 3719 | 1941 | |
mean | 17,740 d | 6361 | 4393 | 2292 | |
Alternative scenario 2 | |||||
p50 | 11,554 d | 4143 | 2861 | 1493 | |
p75 | 10,398 d | 3729 | 2575 | 1344 | |
p90 | 8858 | 3176 | 2194 | 1145 | |
mean | 10,546 d | 3781 | 2611 | 1363 | |
Alternative scenario 3 | |||||
p50 | 7728 | 2771 | 1914 | 999 | |
p75 | 7048 | 2527 | 1745 | 911 | |
p90 | 6162 | 2210 | 1526 | 796 | |
mean | 7422 | 2661 | 1838 | 959 |
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Liu, Z.; Bian, X.; Zhao, Y.; Liang, J.; Zhang, L.; Zhou, P.; Mao, W.; Jiang, D.; Cao, P.; Sun, J. Application of BRAFO-Tiered Approach for Risk–Benefit Assessment of Nut Consumption in Chinese Adults. Foods 2025, 14, 3498. https://doi.org/10.3390/foods14203498
Liu Z, Bian X, Zhao Y, Liang J, Zhang L, Zhou P, Mao W, Jiang D, Cao P, Sun J. Application of BRAFO-Tiered Approach for Risk–Benefit Assessment of Nut Consumption in Chinese Adults. Foods. 2025; 14(20):3498. https://doi.org/10.3390/foods14203498
Chicago/Turabian StyleLiu, Zhujun, Xiangyu Bian, Yingzi Zhao, Jiang Liang, Lei Zhang, Pingping Zhou, Weifeng Mao, Depeng Jiang, Pei Cao, and Jinfang Sun. 2025. "Application of BRAFO-Tiered Approach for Risk–Benefit Assessment of Nut Consumption in Chinese Adults" Foods 14, no. 20: 3498. https://doi.org/10.3390/foods14203498
APA StyleLiu, Z., Bian, X., Zhao, Y., Liang, J., Zhang, L., Zhou, P., Mao, W., Jiang, D., Cao, P., & Sun, J. (2025). Application of BRAFO-Tiered Approach for Risk–Benefit Assessment of Nut Consumption in Chinese Adults. Foods, 14(20), 3498. https://doi.org/10.3390/foods14203498