Animal versus plant-based protein and risk of cardiovascular disease and type 2 diabetes: a systematic review of randomized controlled trials and prospective cohort studies

Christel Lamberg-Allardt; Linnea Bärebring; Erik Kristoffer Arnesen; Bright I. Nwaru; Birna Thorisdottir; Alfons Ramel; Fredrik Söderlund; Jutta Dierkes; Agneta Åkesson

doi:10.29219/fnr.v67.9003

Christel Lamberg-Allardt Department of Food and Nutrition, University of Helsinki, Finland
Linnea Bärebring Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
Erik Kristoffer Arnesen Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway
Bright I. Nwaru Krefting Research Centre, Institute of Medicine, University of Gothenburg, Sweden
Birna Thorisdottir Health Science Institute, University of Iceland, Iceland
Alfons Ramel Faculty of Food Science and Nutrition, University of Iceland, Iceland
Fredrik Söderlund Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, the Karolinska Institute, Sweden
Jutta Dierkes Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Norway and Department of Laboratory Medicine and Pathology, Haukeland University Hospital, Norway
Agneta Åkesson Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, the Karolinska Institute, Sweden

DOI: https://doi.org/10.29219/fnr.v67.9003

Keywords: dietary protein, plant protein, cardiovascular disease mortality, incidence of type 1 diabetes, blood lipids

Abstract

Objectives: To systematically review the evidence on the effect of replacing the intake of animal protein with plant protein on cardiovascular disease (CVD) and type 2 diabetes (T2D) and their intermediate risk factors.

Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 12th May 2022 for randomized controlled trials (RCTs) or prospective cohort studies that investigated replacement of animal protein with plant protein from foods. Outcomes were CVDs, T2D, and in RCTs also the effects on blood lipids, glycemic markers, and blood pressure. Risk of bias was evaluated with the Cochrane’s RoB2, ROBINS-I, and USDA’s RoB-NObS tools. Random-effects meta-analyses assessed the effects of plant vs. animal proteins on blood lipids in RCTs. The evidence was appraised according to the World Cancer Research Fund’s criteria.

Results: After screening 15,090 titles/abstracts, full text of 124 papers was scrutinized in detail, from which 13 RCTs and seven cohort studies were included. Eight of the RCTs had either some concern or high risk of bias, while the corresponding evaluation of cohort studies resulted in moderate risk of bias for all seven. Meta-analyses of RCTs suggested a protective effect on total cholesterol (mean difference -0.11 mmol/L; 95% CI -0.22, -0.01) and low-density lipoprotein cholesterol (-0.14 mmol/L; 95% CI -0.25, -0.02) by replacing animal protein with plant protein. The substitution of animal protein with plant protein (percentage of energy intake) in cohort studies was associated with lower CVD mortality (n = 4) and lower T2D incidence (n = 2). The evidence was considered limited-suggestive for both outcomes.

Conclusion: Evidence that the substitution of animal protein with plant protein reduces risk of both CVD mortality and T2D incidence is limited-suggestive. Replacing animal protein with plant protein for aspects of sustainability may also be a public health strategy to lower the risk of CVD mortality and T2D.

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References

1.
Willett W, Rockström J, Loken B, Springmann M, Lang T, Vermeulen S, et al. Food in the Anthropocene: the EAT-Lancet Commission on healthy diets from sustainable food systems. Lancet 2019; 393(10170): 447–92. doi: 10.1016/S0140-6736(18)31788-4

2.
Santo RE, Kim BF, Goldman SE, Dutkiewicz J, Biehl EMB, Bloem MW, et al. Considering plant-based meat substitutes and cell-based meats: a public health and food systems perspective. Front Sustain Food Syst 2020; 4: 134. doi: 10.3389/fsufs.2020.00134

3.
GBD 2019 Viewpoint Collaborators. Five insights from the global burden of disease study 2019. Lancet 2020; 396: 1135–59. doi: 10.1016/S0140-6736(20)31404-5

4.
Zhao L-G, Zhang Q-L, Liu X-L, Wu H, Zheng J-L, Xiang Y-B. Dietary protein intake and risk of type 2 diabetes: a dose-response meta-analysis of prospective studies Eur J Nutr 2019; 58(4): 1351–67. doi: 10.1007/s00394-018-1737-7

5.
Mousavi SM, Jayedi A, Jalilpiran Y, Hajishafiee M, Aminianfar A, Esmaillzadeh A. Dietary intake of total, animal and plant proteins and the risk of coronary heart disease and hypertension: a systematic review and dose-response meta-analysis of prospective cohort studies. Crit Rev Food Sci Nutr 2022; 62(5): 1336–49. doi: 10.1080/10408398.2020.1841730

6.
Naghshi S, Sadeghi S, Willett WC, Esmaillzadeh A. Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies. BMJ 2020; 370: m2412. doi: 10.1136/bmj.m2412

7.
Qi X-X, Shen P. Associations of dietary protein intake with all-cause, cardiovascular disease, and cancer mortality: a systematic review and meta-analysis of cohort studies. Nutr Metab Cardiovasc Dis 2020; 30: 1094–105. doi: 10.1016/j.numecd.2020.03.008

8.
Chen Z, Glisic M, Song M, Aliahmad HA, Zhang X, Moumdjian AC, et al. Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam study and a meta-analysis of prospective cohort studies. Eur J Epidemiol 2020; 35: 411–29. doi: 10.1007/s10654-020-00607-6

9.
Pedersen AN, Kondrup J, Børsheim E. Health effects of protein intake in healthy adults: a systematic literature review. Food Nutr Res 2013; 57: 21245. doi: 10.3402/fnr.v57i0.21245

10.
Christensen JJ, Arnesen EK, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – principles and methodologies. Food Nutr Res 2020; 64: 402. doi: 10.29219/fnr.v64.4402

11.
Høyer A, Christensen JJ, Arnesen EK, Andersen R, Eneroth H, Erkkola M, et al. The Nordic nutrition recommendations 2022 – prioritisation of topics for de novo systematic reviews. Food Nutr Res 2021; 65: 7828. doi: 10.29219/fnr.v65.7828

12.
Arnesen EK, Christensen JJ, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – handbook for systematic reviews. Food Nutr Res 2020; 64: 4404. doi: 10.29219/fnr.v64.4404

13.
Arnesen EK, Christensen JJ, Andersen R, Eneroth H, Erkkola M, Høyer A, et al. The Nordic nutrition recommendations 2022 – structure and rationale of systematic reviews. Food Nutr Res 2020; 64: 4403. doi: 10.29219/fnr.v64.4403

14.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71. doi: 10.1136/bmj.n71

15.
Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021; 372: n160. doi: 10.1136/bmj.n160

16.
Baranska A, Błaszczuk A, Kanadys W, Baczewska B, Jedrych M, Wawryk-Gawda E, et al. Effects of soy protein containing of isoflavones and isoflavones extract on plasma lipid profile in postmenopausal women as a potential prevention factor in cardiovascular diseases: systematic review and meta-analysis of randomized controlled trials. Nutrients 2021; 13: 2531. doi: 10.3390/nu13082531

17.
Sterne JA, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898. doi: 10.1136/bmj.l4898

18.
Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355: i4919. doi: 10.1136/bmj.i4919

19.
Viswanathan M, Patnode CD, Berkman ND, Bass EB, Chang S, Hartling L, et al. Recommendations for assessing the risk of bias in systematic reviews of health-care interventions. J Clin Epidemiol 2018; 97: 26–34. doi: 10.1016/j.jclinepi.2017.12.004

20.
Nutrition Evidence Systematic Review. Risk of bias for nutrition observational studies (RoB-NObs) tool 2019. Available from: https://nesr.usda.gov/sites/default/files/2019-07/RiskOfBiasForNutritionObservationalStudies-RoB-NObs.pdf [cited 6 February 2020].

21.
McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods 2021; 12: 55–61. doi: 10.1002/jrsm.1411

22.
AHRQ. Methods guide for effectiveness and comparative effectiveness reviews. Rockville, MD: Agency for Healthcare Research and Quality; 2014.

23.
Morton SC, Murad MH, O’Connor E, et al. Quantitative Synthesis—An Update. 2018 Feb 23. In: Methods Guide for Effectiveness and Comparative Effectiveness Reviews [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2008-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519365/.

24.
Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.

25.
Bähr M, Fechner A, Krämer J, Kiehntopf M, Jahreis G. Lupin protein positively affects plasma LDL cholesterol and LDL: HDL cholesterol ratio in hypercholesterolemic adults after four weeks of supplementation: a randomized, controlled crossover study. Nutr J 2013; 12: 107. doi: 10.1186/1475-2891-12-107

26.
Bähr M, Fechner A, Kiehntopf M, Jahreis G. Consuming a mixed diet enriched with lupin protein beneficially affects plasma lipids in hypercholesterolemic subjects: a randomized controlled trial. Clin Nutr 2015; 34: 7–14. doi: 10.1016/j.clnu.2014.03.008

27.
Crouse JR, 3rd, Morgan T, Terry JG, Ellis J, Vitolins M, Burke GL. A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern Med 1999; 159: 2070–6. doi: 10.1001/archinte.159.17.2070

28.
Dent SB, Peterson CT, Brace LD, Swain JH, Reddy MB, Hanson KB, et al. Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors. J Nutr 2001; 131: 2280–7. doi: 10.1093/jn/131.9.2280

29.
Frota KMG, dos Santos RD, Ribeiro VQ, Arêas JAG. Cowpea protein reduces LDL-cholesterol and apolipoprotein b concentrations, but does not improve biomarkers of inflammation or endothelial dysfunction in adults with moderate hypercholesterolemia. Nutr Hosp 2015; 31: 1611–19.

30.
Gardner CD, Messina M, Kiaz A, Morris JL, Franke AA. Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial. J Amer Coll Nutr 2007; 26: 669–77. doi: 10.1080/07315724.2007.10719646

31.
Gardner CD, Newell KA, Cherin R, Haskell WL. The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Am J Clin Nutr 2001; 73: 728–35. doi: 10.1093/ajcn/73.4.728

32.
Jenkins DJ, Srichaikul K, Wong JM, Kendall CW, Bashyam B, Vidgen E, et al. Supplemental barley protein and casein similarly affect serum lipids in hypercholesterolemic women and men. J Nutr 2010; 140: 1633–7. doi: 10.3945/jn.110.123224

33.
Lichtenstein AH, Jalbert SM, Adlercreutz H, Goldin BR, Rasmussen H, Schaefer EJ, et al. Lipoprotein response to diets high in soy or animal protein with and without isoflavones in moderately hypercholesterolemic subjects. Arterioscler Thromb Vasc Biol 2002; 22: 1852–8. doi: 10.1161/01.ATV.0000033513.18431.A1

34.
McVeigh BL, Dillingham BL, Lampe JW, Duncan AM. Effect of soy protein varying in isoflavone content on serum lipids in healthy young men. Am J Clin Nutr 2006; 83: 244–51. doi: 10.1093/ajcn/83.2.244

35.
Santo AS, Cunningham AM, Alhassan S, Browne RW, Burton H, Leddy JJ, et al. NMR analysis of lipoprotein particle size does not increase sensitivity to the effect of soy protein on CVD risk when compared with the traditional lipid profile. Appl Physiol Nutr Metab 2008; 33: 489–500. doi: 10.1139/H08-023

36.
Steinberg FM, Guthrie NL, Villablanca AC, Kumar K, Murray MJ. Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women. Am J Clin Nutr 2003; 78: 123–30. doi: 10.1093/ajcn/78.1.123

37.
Weiße K, Brandsch C, Zernsdor B, Nkengfack Nembongwe GS, Hofmann K, Eder K, et al. Lupin protein compared to casein lowers the LDL cholesterol: HDL cholesterol-ratio of hypercholesterolemic adults. Eur J Nutr 2010; 49: 65–71. doi: 10.1007/s00394-009-0049-3

38.
Budhathoki S, Sawada N, Iwasaki M, Yamaji T, Goto A, Kotemori A, et al. Association of animal and plant protein intake with all-cause and cause-specific mortality in a Japanese cohort. JAMA Intern Med 2019; 179: 1509–18. doi: 10.1001/jamainternmed.2019.2806

39.
Huang J, Liao LM, Weinstein SJ, Sinha R, Graubard BI, Albanes D. Association between plant and animal protein intake and overall and cause-specific mortality. JAMA Intern Med 2020; 180: 1173–84. doi: 10.1001/jamainternmed.2020.2790

40.
Malik VS, Li Y, Tobias DK, Pan A, Hu FB. Dietary protein intake and risk of type 2 diabetes in US men and women. Am J Epidemiol 2016; 183: 715–28. doi: 10.1093/aje/kwv268

41.
Song M, Fung TT, Hu FB, Willett WC, Longo VD, Chan AT, et al. Association of animal and plant protein intake with all-cause and cause-specific mortality. JAMA Intern Med 2016; 176: 1453–63. doi: 10.1001/jamainternmed.2016.4182

42.
Sun Y, Liu B, Snetselaar LG, Wallace RB, Shadyab AH, Kroenke CH, et al. Association of major dietary protein sources with all-cause and cause-specific mortality: prospective cohort study. J Am Heart Assoc 2021; 10: e015553. doi: 10.1161/JAHA.119.015553

43.
Virtanen HEK, Koskinen TT, Voutilainen S, Mursu J, Tuomainen TP, Kokko P, et al. Intake of different dietary proteins and risk of type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Brit J Nutr 2017; 117: 882–93. doi: 10.1017/S0007114517000745

44.
Voortman T, Chen Z, Girschik C, Kavousi M, Franco OH, Braun KVE. Associations between macronutrient intake and coronary heart disease (CHD): the Rotterdam study. Clin Nutr 2021; 40: 5494–9. doi: 10.1016/j.clnu.2021.08.022

45.
Guasch-Ferré M, Ambika Satija A, Blondin SA, Janiszewski M, Emlen E, O’Connor LE, et al. Meta-analysis of randomized controlled trials of red meat consumption in comparison with various comparison diets on cardiovascular risk factors. Circulation 2019; 139: 1828–45. doi: 10.1161/CIRCULATIONAHA.118.035225

46.
Li SS, Mejia SB, Lytvyn L, Stewart SE, Viguiliouk E, Ha V, et al. Effect of plant protein on blood lipids: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc 2017; 6: e006659. doi: 10.1161/JAHA.117.006659

47.
Zhao H, Song A, Zheng C, Wang M, Song G. Effects of plant protein and animal protein on lipid profile, body weight and body mass index on patients with hypercholesterolemia: a systematic review and meta‑analysis. Acta Diabetol 2020; 57: 1169–80. doi: 10.1007/s00592-020-01534-4

48.
Tian S, Xu Q, Jiang R, Han T, Sun C, Na L. Dietary protein consumption and the risk of type 2 diabetes: a systematic review and meta-analysis of cohort studies. Nutrients 2017; 9: 982. doi: 10.3390/nu9090982

49.
Hu FB. Plant-based foods and prevention of cardiovascular disease: an overview. Am J Clin Nutr 2003; 78(3 Suppl): 544S–51S. doi: 10.1093/ajcn/78.3.544S

Animal versus plant-based protein and risk of cardiovascular disease and type 2 diabetes: a systematic review of randomized controlled trials and prospective cohort studies

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