According to a colleague, his doctor recently recommended avoiding soy foods to reduce inflammation. Since there is evidence at odds with this advice, it is a bit puzzling as to why it was given.
The word inflammation comes from the Latin word inflammare (meaning “to set on fire”). The Roman writer Aulus Cornelius Celsus, who lived in the 1st century AD, was the first to describe the process called inflammation. Inflammation is the reaction of the body against injury or infection and is an important defense and survival mechanism.1 For example, the acute inflammation induced in a host by invading microorganisms is essential for the induction of an appropriate response to the infectious threat and for the repair of damaged tissues.2
However, when inflammation is discussed, typically the conversation focuses on systemic chronic inflammation, not acute inflammation. The latter can lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease, and autoimmune and neurodegenerative disorders.3
Systemic chronic inflammation is low-grade and persistent (as the name suggests) and ultimately causes collateral damage to tissues and organs over time, such as by inducing oxidative stress. There are several routinely used markers of inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-a). Although according to Furman et al.,3 there are presently no standard biomarkers for indicating the presence of health-damaging chronic inflammation.
Why might someone, especially a physician, recommend avoiding soy foods to reduce inflammation? Although only speculation, it could be because of the mistaken belief that soybean oil causes inflammation and conflating soybean oil with soy foods. The claim that soybean oil leads to inflammation is based on its high content of the omega-6 essential fatty acid, linoleic acid. However, research shows that neither soybean oil4 nor linoleic acid5 causes inflammation.
It could also be because most plant-based meat alternatives, including those based on soy, are classified as ultra-processed foods, and observational studies show a link between ultra-processed food intake and inflammation.6,7 However, not only do these associations not establish a causal relationship, but no mechanism for a potential inflammatory effect of ultra-processed foods has been identified.8 Furthermore, the category of ultra-processed foods includes a wide range of foods, from sweetened yogurt to potato chips. Many foods classified this way can be part of a healthful dietary pattern as determined by commonly used nutrient profiling models. And in any event, there are soy foods that are unprocessed or minimally processed, so there is little reason to recommend avoiding soy.
There are considerable data upon which one can evaluate the impact of soy foods on markers of inflammation. The evidence highlighted below represents a few recently published meta-analyses of the clinical data. Collectively, this research not only refutes the notion that soy foods cause inflammation but if anything, suggests they may exert an anti-inflammatory effect, although the evidence isn’t sufficiently robust to reach that conclusion.
2023 meta-analysis involving 31 randomized controlled trials:
- Soy protein supplementation significantly reduced TNF-alpha but had no effect on IL-6 levels. Adding isoflavones to soy protein led to a further reduction in TNF-a.9
2021 meta-analysis involving 18 randomized controlled trials:
- Soymilk significantly reduced systolic and diastolic blood pressure, total and low-density lipoprotein cholesterol, waist circumference, C-reactive protein, and TNF-a. Soymilk had no effect on interleukin-6.10
2021 meta-analysis involving 22 randomized controlled trials:
- In participants with type 2 diabetes, soy product consumption led to a significant reduction in serum concentrations of triglycerides, total cholesterol, low density lipoprotein cholesterol, and C-reactive protein.11
2021 meta-analysis involving 19 randomized controlled trials:
- In postmenopausal women, there was a non-significant effect of soy isoflavones or isoflavones plus protein on serum C-reactive protein concentrations.12
2021 meta-analysis involving 14 randomized controlled trials:
- Overall, soy protein plus isoflavones had a non-significant effect on serum IL-6 concentrations. In subgroup analysis, based on soy isoflavone dosage, it was observed that a combination of soy isoflavones and soy protein could reduce IL-6 levels in studies that used isoflavones with doses >84 mg/day.13
2020 meta-analysis involving 51 randomized controlled trials:
- Soy product supplementation led to a significant reduction in C-reactive protein, but it did not affect IL-6 and TNF-a. Subgroup analysis showed that soy supplementation had a significant impact on decreasing IL-6 and TNF-alpha levels when studies had a long-term intervention (≥12 weeks) and used an isoflavone dose below 100 mg/day.14
1. Rivas F. In this Issue: Inflammation. Cell 2010;140:755,7.
2. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010;140:805-20.
3. Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med 2019;25:1822-32.
4. Messina M, Shearer G, Petersen K. Soybean oil lowers circulating cholesterol levels and coronary heart disease risk, and has no effect on markers of inflammation and oxidation. Nutrition 2021;89:111343.
5. Johnson GH, Fritsche K. Effect of dietary linoleic acid on markers of inflammation in healthy persons: A systematic review of randomized controlled trials Journal of the Academy of Nutrition and Dietetics 2012;112:1029-41.
6. Lane MM, Lotfaliany M, Forbes M, Loughman A, Rocks T, O’Neil A, Machado P, Jacka FN, Hodge A, Marx W. Higher ultra-processed food consumption is associated with greater high-sensitivity C-reactive protein concentration in adults: Cross-sectional results from the Melbourne Collaborative Cohort Study. Nutrients 2022;14.
7. Martins G, Franca A, Viola P, Carvalho CA, Marques KDS, Santos AMD, Batalha MA, Alves JDA, Ribeiro CCC. Intake of ultra-processed foods is associated with inflammatory markers in Brazilian adolescents. Public health nutrition 2022;25:591-9.
8. Tristan Asensi M, Napoletano A, Sofi F, Dinu M. Low-grade inflammation and ultra-processed foods consumption: A review. Nutrients 2023;15.
9. Prokopidis K, Mazidi M, Sankaranarayanan R, Tajik B, McArdle A, Isanejad M. Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis. Br J Nutr 2023;129:759-70.
10. Sohouli MH, Lari A, Fatahi S, Shidfar F, Gaman MA, Guimaraes NZ, Sindi GA, Mandili RA, Alzahrani GA, Abdulwahab RA, et al. Impact of soy milk consumption on cardiometabolic risk factors: A systematic review and meta-analysis of randomized controlled trials. J Functional Foods 2021;83:104499.
11. Asbaghi O, Ashtary-Larky D, Mousa A, Kelishadi MR, Moosavian SP. The effects of soy products on cardiovascular risk factors in patients with Type 2 Diabetes: A systematic review and meta-analysis of clinical trials. Adv Nutr 2021;13:455-73.
12. Hariri M, Ghasemi A, Baradaran HR, Mollanoroozy E, Gholami A. Beneficial effect of soy isoflavones and soy isoflavones plus soy protein on serum concentration of C-reactive protein among postmenopausal women: An updated systematic review and meta-analysis of randomized controlled trials. Complement Thr Med 2021;59:102715.
13. Gholami A, Baradaran HR, Hariri M. Can soy isoflavones plus soy protein change serum levels of interlukin-6? A systematic review and meta-analysis of randomized controlled trials. Phytother Res 2021;35:1147-62.
14. Asbaghi O, Yaghubi E, Nazarian B, Kelishadi MR, Khadem H, Moodi V, Naeini F, Ghaedi E. The effects of soy supplementation on inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials. Cytokine 2020;136:155282.
This blog is sponsored by SNI Global and U.S. Soy.