Genistein, Equol, Cognitive Function and Mood: Twelve-week. (GECFAMc)

Overview

Isoflavones (ISF) are naturally occurring compounds that can provide protective benefits for certain domains of cognitive function. Studies on the prevalence of cognitive decline and cancers in the Asian diet-eating areas of the world have investigated the effects of the ISFs and how they affect human bodies and brains. Previous literature has shown that ISFs are capable of activating oestrogen receptors in brains that provide protection in terms of long-term potentiation as well antioxidation, anti-inflammatory and promoting the growth and interaction of neurons (e.g., BDNF upregulation). Genistein is a bioactive ISF having been shown to provide a strong protective response in our brains and other aspects of healthcare; Equol is a metabolite of Daidzein and is thought to provide a similar (or stronger) response than Genistein due to its receptor binding strength. Not everyone is capable of digesting Equol from other Isoflavones (Daidzein) and therefore supplementing this directly could provide neurological benefits at a similar level, if not stronger than, Genistein. This twelve-week three-arm study will aim to evaluate the efficacies of two ISFs (Genistein and Equol) versus a control group. ISF are "Generally Recognised As Safe" ("GRAS") molecules by the United States of America's classification regulatory commission the Federal Drug Administration as well as deemed "Safe" by the European Food Safety Authority (EFSA). Participants will be required to undertake 4 one-hour-long sessions. Interventions will be taken once daily. This investigative team hypothesise that both ISFs will elicit significant positive changes in cognitive functions, specifically to spatial/verbal working memory, executive function, and speed of processing and measures of mood with a variation in effect due to age likely, the lacking restriction for age will allow for this as a covariate dependent on recruitment outcome.

The design of this study is as a three-arm, placebo controlled, double-blind with between-groups comparison. Adult participants aged 18 years old and over will be recruited to the study from the local community (see Appendix H for recruitment poster). After demonstrating an initial interest in the study, participants will be sent the participant information sheet (Appendix A), a health and lifestyle questionnaire (Appendix C), and FFQ to assess habitual diets, supplements and medications (Appendix D). A screening interview will be used to answer the health and lifestyle questionnaire and participants who meet the screening criteria will be able to undergo a practice session where they will sign a consent form (Appendix B) and familiarise themselves with the cognitive tasks and mood questionnaires. Recruitment materials will include posting posters advertising (Appendix H) as well as posts on pertinent social media outlets (such as Reddit page r/Reading) Following a this screening session wherein the researchers will check exclusion/inclusion criteria have been met; participants will be quasi-randomly allocated to intervention based on age and sex, consisting of a control group (maltodextrin), a genistein group (70mg/day) and an equol group (70mg/day). Participants will also undergo a familiarisation session with the computerised software. Return appointments will be made for their study days and participants will be reminded of their right to withdraw from the study at any point. Helplines and web links with support and advice will be provided (Mind, Alzheimer's Society, Dementia UK) alongside advice to contact their GP should they require medical support. On the first testing day (baseline), participants will attend the laboratory after consuming their standard breakfast, but to refrain from consuming any caffeine-containing products (researchers will ask participants to consume the same breakfast on their second test day). Upon arrival at the University, participants will be asked to complete a battery of cognitive tasks and to complete some mood questionnaire. On completion of the battery, the participants will be supplied with their allocation of intervention and asked to consume one capsule every day for a 12-week period. After 6 and 12 weeks of consuming the intervention, subjects will return to the lab for their 2nd \& 3rd study days. On these test days, subjects will be asked not to consume their intervention until after testing has occurred. Here the researchers will follow the same protocol as for the 1st study day, where a single set of cognitive tests and mood measures will be completed. At the end of the trial, pots of pills will be returned to researchers and compared against the expected number of remaining pills to measure adherence. The task battery is composed of cognitive tests and measures of mood, which previous data have shown to be sensitive to nutritional interventions chronically. More generally, the cognitive tests are categorised into one of three key cognitive domains, speed of processing/memory/executive function whilst changes in mood will be measured using the PANAS.