Effects of Annurca apple polyphenols on cholesterol excretion
| ISRCTN | ISRCTN13396702 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13396702 |
| Secondary identifying numbers | 123501 |
- Submission date
- 07/11/2017
- Registration date
- 09/11/2017
- Last edited
- 10/11/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Metabolic syndrome is a serious risk factor for cardiovascular disease (heart disease) such as arteriosclerosis and is caused by hyperlipidemia (high levels of lipids in the blood), hyperglycemia (high blood sugar), and hypertension (high blood pressure). Arteriosclerosis (the thickening and hardening of the artery walls) is related to cardiovascular disease and cerebral infarction (when there is a blockage of the arteries that deliver blood to the brain), which are widely recognized as major public health problems. Reducing the risk of arteriosclerosis, especially dyslipidemia (abnormal amount of lipids in the blood), which was reported to be the strongest risk factor for arteriosclerosis, is extremely important. In some patients, the major abnormality in dyslipidemia is a postprandial serum triglyceride and cholesterol elevation (high levels of sugar and cholesterol after eating). In previous reports, administration of tea polyphenols (micronutrients) improved blood lipid levels and promoted lipid excretion in an animal study, while prevented postprandial serum triglyceride elevation in a clinical study. These reports suggest that tea polyphenols have a lipid excretion (removal) effect. Previous authors have demonstrated that the addition of tea catechins (a natural type of phenol and antioxidant) galloyl moiety to a bile salt micellar solution precipitated (separated) cholesterol and decreased the micellar solubility of cholesterol in a dose-dependent manner. In contrast, green tea catechins without a galloyl moiety did not precipitated cholesterol. Interestingly, apple procyanidins (apple polyphenols) are oligomeric (consisting of only a few) compounds consisting of catechin monomeric units. Specifically, dimeric procyanidins are the most structurally similar to the green tea catechins with a galloyl moiety. Therefore, it could be hypothesised that these may play a major role as regards our observed effects of apple extract samples on in vitro cholesterol micellar solubility. Specifically, the antioxidant composition and in vitro effects on cholesterol metabolism of polyphenolic extracts from Annurca apple, has been evaluated. By comparing experimental data with those from more common commercial apple cultivars, Annurca apple exhibited the highest polyphenolic concentration, while results obtained by incubating human hepatocellular liver carcinoma (HepG2) cell lines with apple extracts, indicated Annurca apple as the most effective in reducing cell cholesterol uptake, enhancing LDL-C receptor binding activity, and increasing cell medium Apo-AI concentration. The aim of the present study is to evaluate the effects of Annurca apple polyphenolic extract on intestinal cholesterol solubility in healthy subjects.
Who can participate?
Men and women between 18-83 years of age.
What does the study involve?
Participants are provided with a food frequency questionnaire at the beginning of the study. Participants are randomly divided into two groups (each one of 25 subjects, 15 men and 10 women).
They are followed by a cross-over design including 7-day washout periods and 10-day treatment periods. During the treatment periods, each group are given about 370 mg cholesterol a day from two eggs (about 50 g weight each) (185 mg cholesterol each within 30 min after lunch and dinner) and total 1000 mg Annurca apple polyphenolic extract in gastro-resistant capsules at two meals (one 500 mg capsule at each meal). Subjects are allowed to take water freely. All the participants are instructed to maintain their habitual patterns of physical activity throughout the entire study period. The physical characteristics are measured and 1 mL of blood is collected after 12 h fasting in the early morning. The blood samples are collected for biochemical examination at days 8, 18, 25 and 35 of the study period. Fecal samples are collected for the analysis of lipid excretion during the last three days of each treatment period.
What are the possible benefits and risks of participating?
In line with what already reported in literature as regards the effects of apple polyphenols, participants are expected to reveal a positive influence on the balance regarding the circulating lipoproteins. Conversely, no side effects are expected, since the maximum quantity of apple polyphenolic extracts (1000 mg) administered daily is in full accordance with the maximum polyphenolic extract daily intake, through food supplements and novel foods, indicated by the revised form (January 2015) of the Commission Regulation (EC) No. 258/1997, as the safe polyphenolic daily amount compatible with a good health state.
Where is the study run from?
The blood samples are collected by the Samnium Medical Cooperative (Italy) and analysed at the Department of Pharmacy, University of Naples “Federico II” (Italy).
When is the study starting and how long is it expected to run for?
October 2017 to January 2018
Who is funding the study?
1. Samnium Medical Cooperative (Italy)
2. University of Naples “Federico II” (Italy)
Who is the main contact?
Professor Gian Carlo Tenore
Contact information
Scientific
University of Naples
Via Domenico Montesano, 49
Naples
80131
Italy
 ORCID ID |
0000-0002-0251-9936 |
|---|---|
| Phone | +39 (0)81678610 |
| giancarlo.tenore@unina.it |
Study information
| Study design | Dietary intervention trial parallel randomised cross-over open controlled study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet: Gian Carlo Tenore giancarlo.tenore@unina.it |
| Scientific title | Effects of Annurca apple polyphenolic extract on intestinal cholesterol solubility in healthy subjects: A monocentric, double-blind, randomised, placebo-controlled, cross-over study |
| Study acronym | AMD |
| Study hypothesis | Annurca apple contains oligomeric procyanidins, mainly dimeric compounds, which are structurally similar to tea galloylated catechins for which the capacity to decrease intestinal cholesterol solubility has been demonstrated. Thus, Aim 1: Evaluate the effects of Annurca apple polyphenolic extract on fecal cholesterol levels in the subjects. Aim 2: Evaluate the effects of Annurca apple polyphenolic extract on plasma levels of TC, LDL-C, HDL-C, TG, in the subjects. |
| Ethics approval(s) | Azienda Ospedaliera Gaetano Rummo Via dell’Angelo, 18/10/2017, ref: 123501 |
| Condition | Metabolic Syndrome (MeTS) |
| Intervention | Participants are randomly allocated into two groups. They are followed by a cross-over design including 7-day washout periods and 10-day treatment periods. During the treatment periods, each group are given about 370 mg cholesterol a day from two eggs (about 50 g weight each) (185 mg cholesterol each within 30 min after lunch and dinner) and total 1000 mg Annurca apple polyphenolic extract in gastro-resistant capsules at two meals (one 500 mg capsule at each meal). |
| Intervention type | Supplement |
| Primary outcome measure | Fecal samples are collected for the analysis of lipid excretion during the last three days of each treatment period. |
| Secondary outcome measures | 1. Clinical history is measured both by interviews and previous clinical data at baseline 2. Anthropometric measures are collected taking height and weight at baseline and at the end of the study period 3. Nutrient intake and dietary habits are measured using a seven day food record validated nutritional questionnaire at baseline and at the end of the study period 4. Blood pressure is measured using a blood pressure cuff at baseline and at the end of the study period 5. 24 hour ambulatory blood pressure is measured using blood pressure cuff at baseline and at the end of the study period 6. Plasma TC is measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period 7. HDL-C is measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period 8. LDL-C is measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period 9. Triglyceride levels are measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period 10. Blood analysis (AST, ALT, γ-GTP, ALP, LDH, Albumin, Total bilirubin, Creatinine) is measured using a Diacron International Free Carpe Diem spectrophotometer (Grosseto, Italy), and commercially available kits from Diacron International at days 8, 18, 25 and 35 of the study period |
| Overall study start date | 18/10/2017 |
| Overall study end date | 04/01/2018 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 83 Years |
| Sex | Both |
| Target number of participants | 50 |
| Participant inclusion criteria | Men and women between 18-83 years of age, of white race, with the following range values of serum cholesterol parameters at baseline (week 0): 1. TC, 200-260 mg/dL 2. HDL-C, 30-45 mg/dL 3. LDL-C, 189-206 mg/dL 4. TG, 170-280 mg/dL 5. Body mass index (BMI) between 18 and 30 kg/m2 |
| Participant exclusion criteria | Healthy adults (males and females) with: 1. Smoking 2. Obesity (BMI >30 kg/m2) 3. Diabetes 4. Hepatic disease 5. Renal disease 6. Heart disease 7. Family history of chronic diseases 8. Drug therapy or supplement intake for hypercholesterolemia 9. Drug therapy or supplement intake containing apple polyphenols 10. Heavy physical exercise (>10 h/week) 11. Pregnant women, women suspected of being pregnant, women who hoped to become pregnant, breastfeeding 12. Birch pollen allergy 13. Use of vitamin/mineral supplements 2 weeks prior to entry into the study 14. Donation of blood less than 3 months before the study |
| Recruitment start date | 17/11/2017 |
| Recruitment end date | 27/11/2017 |
Locations
Countries of recruitment
- Italy
Study participating centres
Castelvenere
80131
Italy
via Domenico Montesano, 49
Naples
80131
Italy
Sponsor information
Hospital/treatment centre
Viale C. Colombo
18 - 82037 Castelvenere (BN)
Benevento
82037
Italy
| Phone | +39 (0)82424244 |
|---|---|
| samnium@samnium.com | |
"ROR" |
https://ror.org/02ww5xj89 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 07/01/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. Additional documents will be available at the Department of Pharmacy, University of Naples “Federico II”, Naples, Italy. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository at the Department of Pharmacy, University of Naples “Federico II”. |
Editorial Notes
10/11/2017: Internal review.
