Iron Supplementation and Side Effects

Overview

The objective of this study is to examine patient-reported gastrointestinal side effects, as well as iron status indicators, inflammatory markers and oxidative stress following administration of ferrous sulfate and iron-enriched Aspergillus oryzae supplementation.

Full Title of Study: “Assessment of Gastrointestinal Symptoms and Other Side Effects After Three Week Oral Ferrous Sulfate and Iron-enriched Aspergillus Oryzae Supplementation in Young Female Subjects”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: April 18, 2018

Detailed Description

Iron deficiency anemia (IDA) afflicts more than 2 billion people globally, making it the most prevalent nutrient disorder, today. Inadequate dietary intake of iron results in consequences like cognitive decline, fatigue, abnormal growth and adverse pregnancy outcomes. These ramifications have associated burdens on economical progression due to decreased market productivity. Inorganic iron supplements like ferrous sulfate (FeSO4) are most commonly used to treat IDA, however known associated side effects occur, decreasing compliancy in individuals. Moreover, inorganic iron salts present a large bolus of iron to the intestinal lumen, resulting in non-transferrin bound iron which leads to systemic inflammation and further exacerbation of chronic diseases. Organic iron compounds have strong potential to be utilized for supplementation, however only under circumstances in which contain high absorbance. Seventeen subjects were randomized in a three-armed, double-blinded crossover design to examine the differences among three treatments (FeSO4, ASP-s and placebo). Outcomes will be to assess acute inflammatory proteins, oxidative stress, iron status indicators, non-transferrin bound iron and gastrointestinal-related side effects.

Interventions

  • Dietary Supplement: Ferrous sulfate
    • 65 mg Fe as ferrous sulfate
  • Dietary Supplement: Aspiron
    • 65 mg Fe as iron-enriched koji culture, called AspironTM
  • Other: Placebo
    • Contains maltodextrin.

Arms, Groups and Cohorts

  • Experimental: Ferrous sulfate
    • Subjects will take a 65 mg Fe capsule of ferrous sulfate, once daily for 21 consecutive days. The first treatment capsule will be consumed with a semi-purified meal (egg albumin, sugar, vanilla, maltodextrose and corn oil) and will have blood drawn hours 0, 1, 2, 3, 4, 6 and 8 post consumption. Serum will be used to determine non-transerrin bound iron, serum iron and percent saturation. Throughout the treatment period, subjects are informed to consume the capsule with food and report symptoms in an online questionnaire. Following three weeks treatment, participants return for a blood draw and oxidative stress indicators are measured. A three week washout period with placebo treatment takes place between treatment crossover.
  • Experimental: Aspiron
    • AspironTM which is an iron-enriched supplement will follow the same guidelines and protocol as ferrous sulfate arm. Equivalent 65 mg Fe per capsule will be administered to participants.
  • Placebo Comparator: Placebo
    • Participants will follow the same description for the other two experimental treatment groups. Capsules will be given to subjects in opaque formation, therefore will be unable to differentiate the iron supplements.

Clinical Trial Outcome Measures

Primary Measures

  • Area under the serum iron curve over 8 hours
    • Time Frame: 0,1,2,3,4,6 and 8 hours
    • Serum iron concentrations (µM) measured over 8 hours following consumption of either Ultimine, FeSO4, or placebo capsules at baseline (0h).
  • Area under the NTBI curve over 8 hours
    • Time Frame: 0,1,2,3,4,6 and 8 hours
    • NTBI (µM) concentrations measured over 8 hours following consumption of either Ultimine, FeSO4, or placebo capsules at baseline (0h).
  • Area under the percent transferrin saturation curve over 8 hours
    • Time Frame: 0,1,2,3,4,6 and 8 hours
    • Percent transferrin (%) saturation concentrations measured over 8 hours following consumption of either Ultimine, FeSO4, or placebo capsules at baseline (0h).

Secondary Measures

  • Change in protein carbonyls
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of protein carbonyls (nmol/mL) oxidative stress after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in thiobarbituric acid reactive substances (TBARS)
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of TBARS (µM) oxidative stress after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in hepcidin
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of inflammatory status via hepcidin (ng/mL) after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in C-reactive protein
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of inflammatory status via C-reactive protein (mg/L) after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in serum ferritin
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of iron status through serum ferritin (µg/L) after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in hemoglobin
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of iron status through hemoglobin (g/dL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in hematocrit
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of iron status through hematocrit (%) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in soluble transferrin receptor (sTFR)
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of iron status through sTFR (ng/mL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in total iron binding capacity (TIBC)
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of iron status through TIBC (µg/dL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in glomerular filtration rate (eGFR)
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of kidney function through eGFR (mL/min/1.73m2) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in creatinine
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of kidney function through creatinine (mg/dL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in blood urea nitrogen (BUN)
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of kidney function through BUN (mg/dL) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in aspartate aminotransferase (AST)
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of kidney function through AST (U/L) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Change in alanine aminotransferase (ALT)
    • Time Frame: Baseline and 21 days
    • Change from baseline to 21 days of kidney function through ALT (U/L) production after taking either Ultimine, FeSO4, or placebo for 3 consecutive weeks.
  • Gastrointestinal symptoms
    • Time Frame: 21 days
    • Symptoms questionnaire was distributed 3 days/week over 3 weeks/treatment. Total survey per supplemental treatment included 9 surveys. Participants described how the supplement contributed to gastrointestinal distress, such as, constipation, diarrhea, fatigue, abdominal discomfort, nausea, headaches, and heartburn.

Participating in This Clinical Trial

Inclusion Criteria

  • Age 18-40 – Female – BMI < 30 kg/m2 – Nonsmoker – Non pregnant – Non lactating – No food allergies to wheat or dairy – No history of gastrointestinal diseases/disorders – Willing to discontinue use of vitamin/mineral supplements – No medications that interfere with iron absorption – No blood or plasma donations during study period Exclusion Criteria:

  • History of gastrointestinal diseases or disorders – Donating blood or plasma two weeks prior to study period – On medications interfering with iron absorption – Food allergies to wheat or dairy – Pregnant or lactating – Smoker – Anemic (< 120 g/L) – Ferritin > 40 ug/L

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Iowa State University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Dr. Manju B. Reddy, Professor – Iowa State University
  • Overall Official(s)
    • Manju B Reddy, PhD, Principal Investigator, Iowa State University

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