Soy Isoflavones

Numerous randomized controlled trials have tested the effects of soy isoflavones on cognitive function, though results appeared to vary depending on age, sex, geographic region, treatment formulation, and treatment duration. Our search identified:

• 2 meta-analyses of randomized controlled trials
• 10 clinical trials testing soy isoflavones
• Numerous preclinical studies on possible mechanisms of action

Clinical studies of soy isoflavones suggest they benefit some cognitive functions, though effects varied across studies and by factors such as age, sex, geographic region, treatment formulation, and treatment duration [1; 2; 3]. A 2015 meta-analysis of 10 randomized controlled clinical trials reported that soy isoflavone supplementation significantly improved overall cognitive function and visual memory in people under 60 years old from non-US countries [2]. A 2020 meta-analyses of 16 randomized controlled clinical trials reported that treatment with soy isoflavones improved overall cognitive function and memory [3]. In this meta-analysis, cognitive effects of soy isoflavones were not significantly different based on geographic region (Asia vs non-Asia) or treatment duration, though people under 60 years old appeared to gain more cognitive benefits than older individuals, and higher-dose trials (≥100 mg/day) showed numerically better results than lower-dose trials. Other cognitive functions, such as executive function, attention, working memory, language, and visuospatial reasoning were not significantly improved by soy isoflavones in this meta-analysis.

In a large double-blind randomized controlled trial of postmenopausal women, treatment with isoflavone-rich soy protein for several years improved visual memory, but not other cognitive functions compared to control [4]. More benefits were seen in women between 5–10 years of menopause than those 10 years post-menopause. Other smaller randomized controlled trials in postmenopausal women reported that isoflavone treatment improved episodic memory, attention, and category fluency, but not nonverbal memory, category generation, planning, or rule-learning [5; 6].

In older men and women, soy isoflavones treatment resulted in improved spatial memory and construction, verbal fluency, and dexterity, but worse executive function [7]. In young healthy adults, high soy diet for 10 weeks resulted in significant improvements in short-term and long-term memory and in mental flexibility, but not in attention or category generation compared to those in the control diet [8]. Women, but not men, on the high soy diet also improved in letter fluency and planning. 

Soy isoflavones bind to an estrogen receptor called ERβ, which is expressed in brain regions important for executive function and memory and in preclinical models can lead to improved cognitive functions [9; 10]. Soy isoflavones also exhibit antioxidant and anti-inflammatory activities [11]. See Genistein rating for more details on this specific soy isoflavone.

APOE4 carriers:

In a randomized controlled trial of 59 people with Alzheimer’s disease, APOE4 genotype did not affect the response to soy isoflavone treatment [12]. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page. 

For Dementia Patients

A randomized controlled trial of 59 Alzheimer’s disease patients reported that soy isoflavone treatment (100 mg/day) for 6 months did not significantly improve cognitive function over placebo, despite increased plasma levels of isoflavones [12].

Soy isoflavones are generally considered safe [13]. Numerous randomized controlled trials in menopausal women reported that side effects were not significantly different between soy isoflavone and placebo groups [2; 3; 14]. Adverse events were generally mild [4] and included gastrointestinal and musculoskeletal complaints [2]. One systematic review of over 100 studies in patients with or at risk of breast cancer suggested that while there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (over 100 mg/day) isoflavones can be recommended for breast cancer patients [15]. In a meta-analysis of numerous clinical trials and single-group studies including a total of 1,753 healthy men or men with prostate cancer, treatment with soy foods, soy protein, or soy isoflavones (0-600 mg/day) did not significantly alter levels of total testosterone, free testosterone, estradiol, or estrone [16]. Drug interactions with soy isoflavones are not well-documented [17], but because they bind to estrogen receptors, they may interact with drugs that target the estrogen system.

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

Soy isoflavones are present in soybeans, tofu, fava beans, and other plants. It is also available as a supplement in tablet and capsule forms. Doses that showed improvement in some cognitive functions in clinical studies ranged from 60–100 mg/day [5; 7; 8].

Full scientific report (PDF) on Cognitive Vitality Reports

Genistein rating

1. North American Menopause S (2011) The role of soy isoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL (October 2010). Menopause 18, 732-753.
2. Cheng PF, Chen JJ, Zhou XY et al. (2015) Do soy isoflavones improve cognitive function in postmenopausal women? A meta-analysis. Menopause 22, 198-206.
3. Cui C, Birru RL, Snitz BE et al. (2020) Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 78, 134-144.
4. Henderson VW, St John JA, Hodis HN et al. (2012) Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial. Neurology 78, 1841-1848.
5. Duffy R, Wiseman H, File SE (2003) Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones. Pharmacol Biochem Behav 75, 721-729.
6. Kritz-Silverstein D, Von Muhlen D, Barrett-Connor E et al. (2003) Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study. Menopause 10, 196-202.
7. Gleason CE, Carlsson CM, Barnet JH et al. (2009) A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women. Age Ageing 38, 86-93.
8. File SE, Jarrett N, Fluck E et al. (2001) Eating soya improves human memory. Psychopharmacology (Berl) 157, 430-436.
9. Zhao L, Brinton RD (2005) Structure-based virtual screening for plant-based ERbeta-selective ligands as potential preventative therapy against age-related neurodegenerative diseases. J Med Chem 48, 3463-3466.
10. Turner JV, Agatonovic-Kustrin S, Glass BD (2007) Molecular aspects of phytoestrogen selective binding at estrogen receptors. J Pharm Sci 96, 1879-1885.
11. Kalaiselvan V, Kalaivani M, Vijayakumar A et al. (2010) Current knowledge and future direction of research on soy isoflavones as a therapeutic agents. Pharmacogn Rev 4, 111-117.
12. Gleason CE, Fischer BL, Dowling NM et al. (2015) Cognitive Effects of Soy Isoflavones in Patients with Alzheimer's Disease. J Alzheimers Dis 47, 1009-1019.
13. Munro IC, Harwood M, Hlywka JJ et al. (2003) Soy isoflavones: a safety review. Nutr Rev 61, 1-33.
14. Chen MN, Lin CC, Liu CF (2015) Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric 18, 260-269.
15. Fritz H, Seely D, Flower G et al. (2013) Soy, red clover, and isoflavones and breast cancer: a systematic review. PLoS One 8, e81968.
16. Reed KE, Camargo J, Hamilton-Reeves J et al. (2021) Neither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studies. Reproductive toxicology 100, 60-67.
17. Soy. Drugs.com.