Multiple Daily Condensed Tannin Supplementation and Iron Bioavailability: The Tannin Dose Response Trial

Long-term, Multiple Daily Condensed Tannin Supplementation in Increasing Concentrations Does Not Affect Iron Status or Bioavailability: Results From the Tannin-dose Response Trial.

Tannins are known to inhibit iron absorption through formation of insoluble tannin-mineral complexes, and have thus been termed 'antinutritional.' Despite this, there is evidence that adaptation to similar antinutritional factors is possible when consumed over time. Limitations in current studies include short (single meal) duration, and use of incongruent tannin types from the condensed tannins that are commonly consumed. If adaptation to tannins does happen, it may be due to salivary proline-rich proteins, which have been found to be protective of iron status in animal models. The primary objectives of this study are: 1) To determine whether condensed tannins impact iron bioavailability or status when consumed in multi-dose, multiple daily supplements and 2) to test whether salivary protein production may impact iron bioavailability with tannin supplementation. Secondary objectives included assessment of the reliability of astringency as a measure of salivary protein production and iron absorption.

The study has been conducted in an iron absorption study of 11 women, aged 18-35 years old, to determine iron bioavailability with supplementation of 0.03, 0.25, and 1.5 g 95% proanthocyanidin rich grape seed extract before and after regular, three times daily supplementation for four weeks. Each participant consumed all three concentrations of supplement over the 26-week study, with a two-week washout between interventions. Direct iron absorption was measured using area under the curve. Iron status was measured by changes in hemoglobin and ferritin, and was adjusted by participant c-reactive protein levels. Salivary samples were collected before and after supplement consumption during meal challenges, and analyzed on HPLC. Astringency testing was conducted at the end of each meal challenge. Iron absorption and status markers were analyzed by ANOVA, and mixed-modeling followed by pairwise comparison by least significant differences. Pearson's correlations were used to correlated salivary proteins and astringency with iron bioavailability.

The present study will provide important information regarding the approximate influence of condensed tannin consumption on iron bioavailability and storage over time, at different doses. Data will also help to delineate possible physiological mechanisms underlying tannin adaptation and possible ways to detect individuals who better adapt than others.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Iron Deficiency Anemia
• Intervention / Treatment: Dietary supplement: 95% condensed proanthocyanidins from grape seed extract

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Manhattan, Kansas, United States, 66502
      • Physical Activity and Nutrition Research Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female, 18-35 years old
• Non-obese BMI (18-29.9)
• Signed informed consent

Exclusion Criteria:

• Oral disease
• Gastrointestinal disease
• Tobacco user
• Heavy alcohol user
• Pregnancy (assessed by pregnancy test)
• Lactation
• Medications affecting iron bioavailability
• Vitamin or mineral supplementation (other than vitamin B12)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.03 mg 95% condensed proanthocyanidin; 0.03 g 95% condensed proanthocyanidins from grape seed extract at week 0 0.03 g 95% condensed proanthocyanidins from grape seed extract at week 4	Dietary supplement: 95% condensed proanthocyanidins from grape seed extract; 0.03, 0.25, and 1.5 g 95% condensed proanthocyanidins from grape seed extract consumed three times daily for 4 weeks each
Experimental: 0.25 g 95% condensed proanthocyanidin; 0.25 g 95% condensed proanthocyanidins from grape seed extract at week 0 0.25 g 95% condensed proanthocyanidins from grape seed extract at week 4	Dietary supplement: 95% condensed proanthocyanidins from grape seed extract; 0.03, 0.25, and 1.5 g 95% condensed proanthocyanidins from grape seed extract consumed three times daily for 4 weeks each
Experimental: 1.5 g 95% condensed proanthocyanidin; 1.5 g 95% condensed proanthocyanidins from grape seed extract at week 0 1.5 g 95% condensed proanthocyanidins from grape seed extract at week 4	Dietary supplement: 95% condensed proanthocyanidins from grape seed extract; 0.03, 0.25, and 1.5 g 95% condensed proanthocyanidins from grape seed extract consumed three times daily for 4 weeks each

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in baseline to endline area under the curve after meal challenge at weeks 0 and 4 of each intervention	Change in area under the curve will be measured after administration of test meal including ferrous sulfate and condensed tannin supplementation at weeks 0 and 4	Baseline and 4 weeks
Change in baseline to endline hemoglobin and serum ferritin at weeks 0 and 4 of each intervention	Change in ferritin and hemoglobin will be measured before administration of test meals at weeks 0 and 4	Baseline and 4 weeks
Change in salivary proteins at weeks 0 and 4 of each intervention	HPLC determination of salivary proteins will be analyzed from saliva collected before and after test meals at weeks 0 and 4 of each intervention	Baseline and 4 weeks

Collaborators and Investigators

• Sponsor: Kansas State University
• Collaborators: United States Department of Agriculture Foreign Agricultural Service
• Investigators: Principal Investigator: Brian L Lindshield, Ph.D., Kansas State University

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2016
• Primary Completion (Actual): December 10, 2016
• Study Completion (Actual): December 10, 2016

Study Registration Dates

• First Submitted: January 23, 2017
• First Submitted That Met QC Criteria: January 24, 2017
• First Posted (Estimate): January 25, 2017

Study Record Updates

• Last Update Posted (Estimate): January 25, 2017
• Last Update Submitted That Met QC Criteria: January 24, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: antinutrients; tannins; proanthocyanidins; salivary proline-rich proteins
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Phytogenic; Antiprotozoal Agents; Antiparasitic Agents; Antioxidants; Proanthocyanidin; Grape Seed Extract; Procyanidin
• Other Study ID Numbers: PRPTanninTrial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No