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Discovering markers of flavonoid intake: The Flavi-MARKER study

Validity of novel urinary biomarkers of flavan-3-ol intake in healthy participants: A randomised, 5-way cross-over trial

Status
Completed
Phases
Unknown
Study type
Interventional
Source
ANZCTR
Registry ID
ACTRN12619001553167
Acronym
n.a.
Enrollment
16
Registered
2019-11-12
Start date
2020-12-01
Completion date
2021-06-10
Last updated
2023-01-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Recommendations to increase intakes of foods rich in flavonoids have the potential to improve population health and reduce cardiovascular disease-related mortality. Flavan-3-ols are the most abundant subclass of flavonoids in the diet and are found in abundance in cocoa, apples, and tea. Currently, flavan-3-ol intake is estimated from food frequency questionaires. There is a crucial need for quality biomarkers of intake as a means of overcoming food questionnaire and food database limitations. Recently, a microbiome-derived flavan-3-ol catabolite, gamma-valerolactone (gVL), has emerged as a promising candidate. The primary aim of the proposed project is to establish the suitability of gVLs as biomarkers of flavan-3-ol intake.

Interventions

This is a randomised, controlled, 5-way cross-over designed acute intervention trial. Volunteers will be randomised to receive each of the four interventions, plus control, in a random order: 1. Black tea – 1 cup of black tea, steeped for two minutes in 250ml of freshly boiled water and served with the tea bag out (no milk), 3 x per day, for one day. 2. Green tea – 1 cup of green tea, steeped for two minutes in 250ml of freshly boiled water and served with the tea bag out (no milk), 3 x per d

This is a randomised, controlled, 5-way cross-over designed acute intervention trial. Volunteers will be randomised to receive each of the four interventions, plus control, in a random order: 1. Black tea – 1 cup of black tea, steeped for two minutes in 250ml of freshly boiled water and served with the tea bag out (no milk), 3 x per day, for one day. 2. Green tea – 1 cup of green tea, steeped for two minutes in 250ml of freshly boiled water and served with the tea bag out (no milk), 3 x per day, for one day. 3. Apple – 1 Pink Lady apple (~200g), with the skin on and eaten to the core, 3 x per day, for one day. 4. Cocoa – 1 CocoaVia cocoa sachet (4.5g) in 200ml of hot water, 3 x per day, for one day. Participants will be provided with the tea/apple/cocoa as well as instructions to prepare and consume their drinks/food during the intervention period. Volunteers will be asked to maintain a low-flavan-3-ol diet, during each data intervention period, as a way of reducing the ‘background noise’ from their usual diet. To achieve this, volunteers will be provided with all meals for the intervention days as well as the meal the night before. Meals will be prepared by the metabolic research kitchen at Edith Cowan University. These will be prepared using foods that contain low levels of flavan-3-ols (i.e., <1mg/serve) and all participants will consume the same meals before each visit, apart from selected available snacks to raise energy intake according to individual appetite. Breakfast will be a selection from three low-flavonoid meals: cornflakes with milk/rice krispies with milk/eggs on white toast. A low-flavonoid lunch will be provided consisting of white bread with either pumpkin soup or chicken and sweet corn soup. Dinner will be a selection of: meat pie/mince samosas/chicken parcels. Snacks will consist of the following options: custard cream biscuit/plain yoghut/babybel cheese/tinned pineapple/popcorn. The low (poly)phenolic diet contains less than three servings of fruit and vegetables per day while, water will be provided ad labium. Volunteers will also be provided with an example menu and a list of foods to limit intake of (i.e., high flavonoid foods), on the day preceding the intervention (List 1 - 3). To monitor adherence, participants will keep a diary detailing: the time the intervention was consumed, the preparation of the intervention and the maintenance of the low flavan-3-ol diet. These diaries will be cross checked when the participants return their urine samples. There will be a minimum 2 day wash out between each intervention. List 1. Foods participants will be asked to avoid. Coffee Red wine White wine Rose´ wine Sherry wine All Beer Black tea Green tea Oolong tea Rooibos tea Peppermint tea Chamomile tea Any other tea All fruit juices Apple cider All chocolate All chocolate containing foods Cacao beans Chocolate drink All fruit juice All jams All dried fruit Apple Banana Grape Raisin Current Plum Prune Dates Cranberry Kiwi Pear Blackberry Blueberry Strawberry Raspberry Nectarine Mango Cherry Apricot Peach Garlic Red onion White onion Lettuce Olives Shallots Capers Broccoli Tomato Capsicum Asparagus Carrot Spinach Artichokes Herbs and spices Capers Kale Avocado Potato Sprouts Green bean Sorghum- flour Brown rice All whole- meal flour or rye Green bean Broad bean Kidney bean Black bean Soybean Soy products Tempeh Tofu Buckwheat Almond Pistachio Pecan Peanut Hazelnut Walnut Flaxseed meal Chestnut List 2. A list of foods suitable for consumption Water Soda water Milk Eggs Red meat White meat All Seafood meats All plain cheese All plain yoghurt Butter (use for cooking) Plain ice-cream Plain yoghurt Lemon Melon Orange Pineapple Vegemite Plain sugar Salt Cauliflower Pumpkin Peas Corn Button-Mushroom Cucumber Zucchini Celery White bread White pastry White rice White pasta Chickpea Quick oats Popcorn Plain biscuits Corn flakes Plain Weetabix List 3. A description of suitable meals Breakfast Choice of: cornflakes with milk / rice krispies with milk / bacon, eggs, mushroom & toast / plain yoghurt with watermelon or honey / porridge / toast with butter & vegemite + orange / pancake with honey Lunch Choice of: Toasted chicken or steak sandwich / cheese sandwich / chicken soup with bread / eggs and rice Evening Meal Choice of: chicken and gravy pie with pumpkin and butter side / macaroni cheese / steak and kidney pie with cauliflower / beef stew / ham burger and chips / salmon, white rice and zucchini Meal Accompaniments Selection of: plain rice / bread with butter / peas / corn Snacks Selection of: custard cream biscuits / cheese scone / toffee yoghurt / crumpets / Babybel cheese / mini cheddars / melon / corn chips / popcorn / tinned pineapple Drinks Selection of: Water / Soda Water / Milk Dessert Plain ice-cream

Sponsors

University of Western Australia
Lead SponsorUniversity

Study design

Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Diagnosis
Masking
Blinded (masking used) (Investigator)

Eligibility

Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
Yes

Inclusion criteria

Inclusion criteria: • Men and women between 18 and 75 years of age • No prescription medications • BMI 18.5 – 30 kg/m2 • Previously consumed cocoa, tea and apples with no adverse reactions

Exclusion criteria

Exclusion criteria: • Adults unable to consent • Body mass index less than 18.5 or greater than 30 kg/m2 • Systolic blood pressure less than 150 mmHg • Diastolic BP less than 100 mmHg • Diagnosed diabetes • Current or recent (less than 12 months) smoking • History of cardiovascular or peripheral vascular disease • Use of blood pressure lowering or cholesterol lowering medication • Psychiatric illness or other major illnesses such as cancer • Alcohol intake greater than 210 g per week for women and greater than 280 g per week for men • Women who are lactating, pregnant or wishing to become pregnant during the study. • Inability to attend clinic/office visits • Use of antibiotics (within previous 3 months) • Inability or unwillingness to follow the study protocol • Any dietary allergies to cocoa, tea and apples or any ingredients in the standardised meals • GI tract disorders, previous GI surgery (except appendectomy) • Self-reported malabsorption (e.g. difficulty digesting or absorbing nutrients from food, potentially leading to bloating, cramping or gas) • Diarrhoea within the last 3 months • Vegetarian, Vegan, food faddists, individuals using non-traditional diets, on a weight loss diet or individuals following diets with significant deviations from the average diet • Currently participating in another clinical or dietary intervention study

Outcome results

None listed

Source: ANZCTR · Data processed: Feb 4, 2026