Cystatin SN Binds to Phytic Acid and Predicts Non-heme Iron Bioavailability

Salivary Cystatin SN Binds to Phytic Acid and is a Predictor of Non-heme Iron Bioavailability With Phytic Acid Supplementation

Phytic acid is a known inhibitor of iron bioavailability, although long term studies have suggested possibly exaggerated findings compared to single meal studies, pointing to phytic acid adaptation over time. Salivary proline-rich proteins have been found to reduce tannin-iron chelation, but studies have not explored changes in salivary proteins that may result in phytic acid adaptation. The primary objectives of this study are: 1) To determine whether phytic acid impacts iron bioavailability or status when consumed over time 2) to test whether salivary protein production may impact iron bioavailability with phytic acid supplementation, and 3) to explore in vitro phytic acid salivary binding. Secondary objectives included assessment of the reliability of astringency as a measure of salivary protein production and iron absorption.

The study was conducted in an iron absorption study of 7 women, aged 18-35 years old, to determine iron bioavailability with supplementation of 350 mg phytic acid before and after regular, three times daily supplementation for four weeks. 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 and by ELISA. Astringency testing was conducted at the end of each meal challenge. In vitro saliva-phytic acid modeling was explored on HPLC, MALDI-TOF, and ELISA. 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 phytic acid consumption on iron bioavailability and storage over time in regards to salivary proteins. It will also give context to the role of salivary proteins with phytic acid consumption over time. Data will also help to delineate possible physiological mechanisms underlying phytic acid 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: phytic acid

• Study Type: Interventional
• Enrollment (Actual): 7
• 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: 14 years to 31 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 350 mg phytic acid; 350 mg phytic acid (inositol hexaphosphate) at week 0 (before supplementation) and at week 4 (after supplementation)	Dietary supplement: phytic acid; 350 mg phytic acid (inositol hexaphosphate) three times daily for four weeks; Other Names: inositol hexaphosphate

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 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 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 intervention	HPLC determination of salivary proteins will be analyzed from saliva collected before and after test meals at weeks 0 and 4 of the intervention	Baseline and 4 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 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: Phytic acid; Cystatin; Salivary proline-rich protein; antinutrient
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Inositol
• Other Study ID Numbers: SPPhyticAcidTrial

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