Clinical trial NCT01293175: Whole Grain Polyphenol Bioavailability and Effects on Health
Official title: Whole Grain Polyphenol Bioavailability and Effects on Inflammatory, Oxidative and Hormonal Status
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Overweight
Keywords: whole grains
polyphenols
overweight
bioavailability
antioxidant status
inflammation
Lead sponsor: Federico II University
Sponsor class: OTHER
First posted: 2011-02-10
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Whole grains (WG) contain numerous physiologically bioactive compounds, a key group being polyphenolic compounds such as ferulic acid (FA). These whole grain polyphenolic compounds have been shown to have potent antioxidant activity. This study will evaluate bioavailability of WG bioactive compounds and their physiological impact on health outcomes, mainly related to inflammatory, oxidative and hormonal status, in overweight subjects.

Detailed description: Epidemiological evidence indicates that consumption of whole grains (WG) is associated with improved health and decreased risk for common chronic diseases. However there is paucity of intervention data regarding the beneficial effects of WG in vascular health and associated metabolic disorders.

From 2007 up to now five main intervention studies using WG were published. The results from these studies consistently showed no efficacy of WG to modify biochemical parameters in free-living subjects including WG in their habitual diet. Anyway some drawbacks could be found and mainly regarding subject compliance to the treatment and the type of WG-rich foods supplied.

Our working hypothesis is based on WG physiologically bioactive compounds mainly polyphenolic compounds such as ferulic acid (FA). FA is covalently bound to arabinoxylans constituting WG dietary fiber. This structure represents a natural way to carry polyphenol compounds, into the lower gut. A previous work indicated that intestinal microflora particularly Bifidobacteria and Lactobacilli is able to ferment WG polysaccharide moiety (prebiotic effect) and at the same time microbial esterases can release free phenolic acids. The free acids are adsorbed through the colon barrier into the blood. The slow and continuous release of phenolic acids, particularly FA, determines an increase of baseline level of FA in the blood of WG consumers. However no study correlated FA plasma concentration with health parameters such as biomarkers of inflammation, glucose metabolism and oxidative status which may be in turn associated to the CVD risk.

In this framework a controlled, parallel, two arm intervention study will be performed using a WG-rich product that will be selected from those commercially available for having a high content of FA (\>500 mg/kg). The aim of this study is to evaluate the bioavailability of FA over a two month-treatment in overweight subjects and to correlate variation of FA plasma concentrations with biomarkers of oxidative (plasma antioxidant capacity, MDA) and inflammatory (CRP, anti- and pro-inflammatory cytokines) status, with nutritional status and with gastro-intestinal hormones related to appetite and glucose metabolism (ghrelin, PYY, PP, insulin, GLP-1, GIP and leptin). Eighty subjects will be selected in the respect of strict inclusion and exclusion criteria and will be randomized to include WG in opportunely revised individual habitual diet, or to continue with their habitual diet. At baseline, after 1 month and after 2 months from starting the protocol, blood drawings will be performed and urine and feces will be collected from fasting subjects. Gastro-intestinal hormone response and glucose metabolism following a standard meal will be also evaluated at baseline and at 2 months.

Eligibility criteria: Inclusion Criteria:

* 18 - 60 years old, male and female
* Healthy by medical assessment
* Overweight: BMI \> 25 and \< 32 kg/m2
* Habitual diet characterized by i) absence of WG (all dietary carbohydrates derived from refined cereals); ii) absence of pro-biotics; iii) intake of dietary fibre ≤ 10 g/d; iv) intake of fruit and vegetables ≤ 2 portions/die; v)habit to have breakfast
* Sign of a written informed consent

Exclusion Criteria:

* Age \< 18 and \> 60 years old
* Pregnancy or breastfeeding
* Fasting plasma triglycerides ≥ 200 mg/dl and cholesterol \> 200 mg/dl
* Cardiovascular events (AMI and/or stroke) in the last 6 months
* Regular intensive physical activity
* Hypertension
* Intestinal or metabolic diseases/disorders such as diabetic, renal, hepatic, pancreatic or ulcer
* Previous abdominal/gastrointestinal surgery
* Regular consumption of medication
* Antibiotic therapy within 2 months previous the study
* Food allergies and intolerances (celiac disease, lactose intolerance,)
* Concurrent participation or having participated in another clinical trial during the last 3 weeks

Primary outcomes:
measure: Variation of serum polyphenol concentration
timeFrame: 1 year
measure: Variation of plasma lipids
timeFrame: 1 year
Secondary outcomes:
measure: Variation of serum antioxidant capacity
timeFrame: 1 year
measure: Variation of body weight
timeFrame: 1 year
measure: Variation of serum inflammatory marker concentration
timeFrame: 1 year
measure: Variation of fecal microbiota composition
timeFrame: 1 year
measure: Variation of serum gastro-intestinal hormone concentration
timeFrame: 1 year
measure: Variation of blood pressure
timeFrame: 1 year
measure: Variation of body circumferences
timeFrame: 1 year
measure: Variation of body composition
timeFrame: 1 year
Other outcomes:
Locations:
city: Portici
country: Italy
facility: Department of Food Science
Study officials:
affiliation: University of Naples
name: Vincenzo Fogliano, Prof
role: STUDY_DIRECTOR
affiliation: University of Naples
name: Paola Vitaglione, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vitaglione P, Mennella I, Ferracane R, Rivellese AA, Giacco R, Ercolini D, Gibbons SM, La Storia A, Gilbert JA, Jonnalagadda S, Thielecke F, Gallo MA, Scalfi L, Fogliano V. Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber. Am J Clin Nutr. 2015 Feb;101(2):251-61. doi: 10.3945/ajcn.114.088120. Epub 2014 Dec 3.