Impact of a Novel Functional Snack on Perimenopausal Symptoms and Well-being

Impact of a Novel Functional Snack on Perimenopausal Symptoms and Well-being: a Randomised, Double-blinded, Placebo-controlled, Crossover Trial

This is a clinical trial aimed to investigate if a novel phytochemical and fibre-rich snack can improve perimenopausal symptoms and well-being in perimenopausal women aged 40-55 and not on hormone replacement therapy.

Hypothesis: The investigators hypothesise that the phytochemical and fibre-rich snack will improve perimenopausal symptoms via a gut microbiota mediated mechanism.

Main research questions:

Does eating the snack every day lower menopause symptoms such as hot flushes, night sweats, mood changes, and sleep problems? Does the snack improve mood, stress, anxiety, sleep, and overall quality of life? Does the snack improve the balance of bacteria in the gut, and could this be part of how it helps symptoms?

This double-blind, randomised, placebo-controlled crossover trial will assess the effects of daily consumption for 4 weeks of a novel phytochemical- and fibre-rich granola snack created by TulaCode on menopausal symptoms. The effects of the snack will be compared to a calorie-matched placebo snack: a commercially available oat bar low in fibre and polyphenols. The study will also examine the impact of the intervention snack on mood, stress, sleep quality, cognition, depression and anxiety. Participants will be randomly assigned to either the intervention or the placebo snack for 4 weeks followed by a 4-week washout period before crossing over to the alternate snack for another 4 week period. Snacks will be consumed twice daily, and participants will be instructed to maintain their usual diet and physical activity while avoiding additional probiotic, prebiotic, or polyphenol-rich supplements throughout the study.

Participants will attend 4 in-person study visits at King's College London. At baseline, after 4 weeks, after 8 weeks (washout period) and after 12 weeks. Each study visit will take approximately 1 hour. On the day before each study visit, participants will be asked to self-collect their saliva, 24-h urine and stool samples at home, as well as finish a set of online questionnaires, and be fasted for 12 hours prior to their study visit.

Self-collection procedure of participants at home one day before study visits:

1. Collect a total of 6 saliva samples throughout the day to measure cortisol levels and fill the saliva collection booklet.

2. Collect a 24 h urine sample, starting in the morning after the first void urine, and finishing the next day collecting the first urine of the day (morning of the study visit day).

3. Collect a small stool sample throughout the day for gut microbiome analysis.

4. Fill the below online questionnaires:

   1. Positive and Negative Affect Schedule (PANAS-SF) questionnaire
   2. Hospital Anxiety and Depression Scale (HADS)
   3. Menopause Rating Scale (MRS)
   4. Cognitive Failure Questionnaire (CFQ)
   5. Perceived Stress Scale (PSS)
   6. World Health Organisation Quality of Life assessment instrument (EF-WHOQOL-100)

5. Weekly questionnaire, 4 questionnaires per visit:

   1. International Physical Activity Questionnaire (IPAQ)
   2. Pittsburgh Sleep Quality Index (PSQI)
   3. Online 24 h dietary recall (Intake 24)
   4. 24h picture log of meals (OPIS)
   5. Gastrointestinal Symptom Rating Scale (GSRS)
   6. Menopause Rating Scale (MRS)

6. Fill the below paper questionnaires:

   1. Food-Frequency Questionnaire - EPIC (only for visit 2)
   2. Food-Frequency Questionnaire - KCL polyphenol (only for visit 4)

On the morning of each study visit day, participants will bring their self-collected saliva, urine, and stool samples. Any Adverse events will be discussed and recorded. Any concomitant medication will be checked by the researchers that may impact on the eligibility criteria and the early completion of the study. Self-collected samples and completed online questionnaires will be checked. Blood pressure, heart rate and anthropometric measurements will be performed, waist-hip circumference will be measured, and fasting blood samples will be collected.

On Visit 1 (baseline), either intervention snack or a calorie-matched placebo snack will be provided to participants, with the amount should be enough for the 4-week study period. On Visit 3 (after 8 weeks), the crossover snacks will be provided to participants.

At the end of visit 1, 2 and 3, new self-collection kits and a link of online questionnaires will be distributed to participants to be used for next study visit.

Inclusion Criteria:

• Adults aged 40 to 55
• Score 14 or higher on the Menopause Rating Scale
• For intervention purposes, eligible participants are also required to have a mobile phone and be able to read and speak English.

Exclusion Criteria:

• People who consume more than 15g of fibre a day
• People who consume more than 2 cups of coffee or tea a day
• People who consume more than 4 portions (portion = 80g) of fruits and vegetables a day
• People who do not have any intolerances or allergies to the following:
• Any kinds of nuts including tree nuts, peanuts, hazelnuts and coconuts
• Chia seeds
• Pumpkin seeds
• Sunflower seeds
• Dates
• Gluten
• Dairy
• Oats
• Barley
• Soya
• People who smoke or vape or have smoked or vaped in the last 2 years
• People who consume more than 21 drinks a week or have a history of excess alcohol intake
• People with comorbid conditions that may limit participation in the study, such as a history of an acute cardiovascular event, including coronary artery disease, previous myocardial infarction (heart attack), stroke, peripheral artery disease, diabetes mellitus, chronic kidney disease, metabolic syndrome, malignancies, cardiac arrhythmia, renal failure, cardiac failure, uncontrolled hypertension, cancer or major psychiatric or cognitive problems
• People receiving drug treatment for lipid metabolisms (e.g., statins)
• People with a history of long-term use of medicines known to influence glucose metabolism (e.g., corticosteroids) or aspirin
• People taking antihypertensive drugs
• People who take antibiotics or bacterial agents (Probiotics) within 1 month
• People who take vitamin/dietary supplements within 1 month
• Pregnant women, women ready for pregnancy, and nursing mothers
• cardiac arrhythmia
• renal failure
• heart failure (NYHA II-IV)
• diabetes mellitus
• Malignant disease
• People who have participated in a biomedical study within the past 3 months
• Women who require hormone replacement therapy during the development of the protocol.