Genistein and brain health

Genistein

  • Food & Drink
  • Updated July 20, 2018

Genistein is a type of isoflavone (i.e., polyphenol) found in soy products. It preferentially acts on an estrogen receptor thought to play important roles in cognitive functions, menopausal symptoms, and premenstrual syndrome. No studies have tested genistein specifically for preventing cognitive decline, but studies of soy isoflavone treatments that included genistein did find benefit in some cognitive functions for people of specific ages and genders. Genistein intake via diet or supplementation is generally regarded as safe.

Evidence

No clinical trial has tested genistein specifically, though numerous trials have examined the effects of soy isoflavone treatments that included genistein. Our search identified:

  • Numerous randomized clinical trials testing soy isoflavones but not genistein alone
  • 1 observational study
  • Numerous preclinical studies on possible mechanisms of action

Potential Benefit

No clinical trials have tested genistein specifically, though some studies have examined the effects of soy isoflavone treatments in menopausal women (see Soy Isoflavones rating for details).

An observational study of 195 Japanese and 185 Chinese women reported that dietary intake of genistein was not significantly associated with measures of cognitive performance in either ethnic group [1].

Genistein binds to an estrogen receptor called ERβ, which is expressed in brain regions important for executive function and memory [2][3]. Cognitive benefits of genistein have been observed in preclinical models of brain toxicity [4], inflammation [5][6], diabetes-induced cognitive decline [7], Parkinson's disease [8], and Alzheimer's disease [9][10]. In these studies, genistein inhibited cell death [4][10], increased levels of a protein that protects brain cells [4][5], decreased levels of the enzyme that breaks down the neurotransmitter? acetylcholine [6], lowered inflammation [6][7], and prevented mitochondrial dysfunction [11]. In preclinical models of Alzheimer's disease, genistein decreases beta-amyloid? levels [9] and inhibits death of neurons induced by beta-amyloid [12]. These effects have not been confirmed in humans.

For Dementia Patients

No studies have tested genistein specifically in dementia patients. A randomized controlled trial of 59 Alzheimer's disease patients reported that soy isoflavone treatment (100 mg/day) for six months did not significantly improve cognitive function over placebo, despite increased plasma levels of isoflavones [13].

Safety

Genistein is generally considered safe, but most safety data come from large studies with soy isoflavones or dietary consumption of soy products. The largest study that examined genistein specifically was a meta-analysis of seven randomized controlled trials including a total of 670 subjects [14]. In trials lasting two to three years, about 19% of subjects reported gastrointestinal symptoms. Although genistein acts on estrogen receptors, several studies including one lasting three years reported that genistein is not associated with any significant adverse effect on breast density, the uterus, or endometrial thickness. Drug interactions with genistein are not well-documented [15], but because genistein binds to estrogen receptors, it will likely 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.

How to Use

Genistein is found in soybeans, tofu, and fava beans [16]. It is also available as supplements in tablet and capsule forms. Doses that showed improvement in a few cognitive functions in clinical studies ranged from 60–100 mg of soy isoflavones a day, which contains genistein doses of ~52 mg/day [17][18][19]. Genistin, a sugar-bound soy isoflavone that is biologically inactive, can be broken down into a bioavailable form in our digestive tract after exposure to high temperatures, such as cooking [20].

Learn More

A randomized controlled trial is testing the effects of genistein treatment on amyloid beta levels in the cerebral spinal fluid of Alzheimer’s disease patients.

References

  1. Huang MH, Luetters C, Buckwalter GJ et al. (2006) Dietary genistein intake and cognitive performance in a multiethnic cohort of midlife women. Menopause 13, 621-630.
  2. 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.
  3. Turner JV, Agatonovic-Kustrin S, Glass BD (2007) Molecular aspects of phytoestrogen selective binding at estrogen receptors. J Pharm Sci 96, 1879-1885.
  4. Jiang T, Wang XQ, Ding C et al. (2017) Genistein attenuates isoflurane-induced neurotoxicity and improves impaired spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt signaling. Korean J Physiol Pharmacy 21, 579-589.
  5. Lee HJ, Lim SM, Ko DB et al. (2017) Soyasapogenol B and Genistein Attenuate Lipopolysaccharide-Induced Memory Impairment in Mice by the Modulation of NF-kappaB-Mediated BDNF Expression. J Agric Food Chem 65, 6877-6885.
  6. Mirahmadi SM, Shahmohammadi A, Rousta AM et al. (2017) Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects. Cytokine.
  7. Rajput MS, Sarkar PD (2017) Modulation of neuro-inflammatory condition, acetylcholinesterase and antioxidant levels by genistein attenuates diabetes associated cognitive decline in mice. Chem Biol Interact 268, 93-102.
  8. Arbabi E, Hamidi G, Talaei SA et al. (2016) Estrogen agonist genistein differentially influences the cognitive and motor disorders in an ovariectomized animal model of Parkinsonism. Iran J Basic Med Sci 19, 1285-1290.
  9. Bonet-Costa V, Herranz-Perez V, Blanco-Gandia M et al. (2016) Clearing Amyloid-beta through PPARgamma/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer's Disease. J Alzheimers Dis 51, 701-711.
  10. Wang Y, Cai B, Shao J et al. (2016) Genistein suppresses the mitochondrial apoptotic pathway in hippocampal neurons in rats with Alzheimer's disease. Neural Regen Res 11, 1153-1158.
  11. Sadhukhan P, Saha S, Dutta S et al. (2017) Nutraceuticals: An emerging therapeutic approach against the pathogenesis of Alzheimer's disease. Pharmacy Res.
  12. Zeng H, Chen Q, Zhao B (2004) Genistein ameliorates beta-amyloid peptide (25-35)-induced hippocampal neuronal apoptosis. Free Radic Biol Med 36, 180-188.
  13. 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.
  14. Liu Y, Li J, Wang T et al. (2017) The effect of genistein on glucose control and insulin sensitivity in postmenopausal women: A meta-analysis. Maturitas 97, 44-52.
  15. Soy. Drugs.com.
  16. (2018) Genistein. DrugBank.
  17. 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 Behave 75, 721-729.
  18. File SE, Jarrett N, Fluck E et al. (2001) Eating soya improves human memory. Psychopharmacology (Berl) 157, 430-436.
  19. 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 Aging 38, 86-93.
  20. Devi KP, Shanmuganathan B, Manayi A et al. (2016) Molecular and Therapeutic Targets of Genistein in Alzheimer's Disease. Mol Neurobiol.