Effect of Ferrous iROn and cUrcumin sTatus on Inflammatory and Neurotrophic markErs (Fe-ROUTINE)

The Effect of HydroCurc™ Curcumin and Ferrous Iron Supplementation on Iron Status and Inflammatory and Neurotrophic Marker Levels in Healthy Adults

INTRODUCTION: Iron is a vital nutrient for many physiological processes including DNA production, oxygen transport and neuronal processes. However, several factors limit iron absorption including: limited bioavailability of iron (dietary or supplementation sources), can be subject to dietary iron inhibitors (e.g. calcium). Excess iron can cause cellular oxidative stress in the body.

Curcumin is an active component found in turmeric, known for its anti-oxidant and anti-inflammatory properties. Co-administration of iron and curcumin may influence iron, inflammatory status and/or neurotrophic markers in the body.

Study Overview

• Status: Completed
• Conditions: Iron Deficiency (Without Anemia)
• Intervention / Treatment: Dietary supplement: Ferrous Sulphate 65 mg; Dietary supplement: Curcumin; Other: Placebo (Curcumin); Other: Placebo (Ferrous Sulphate); Dietary supplement: Ferrous Sulphate 18mg

Detailed Description

Intervention study with five parallel treatment groups in a randomised, double-blind, placebo-controlled design.

Study population: Healthy Participants (Male or Female) will receive daily supplements (active or equivalent placebos) for 6 weeks (42 days)

Biological samples (blood and urine samples) are collected at baseline visit (day 1), mid-point (day 21) and end-point (day 42). In addition, pertinent questionnaires (Visual Analogue Scale-Fatigue [VAS-F] and oral iron supplement questionnaire will be collected at the aforementioned time points.

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W1W 6UW
    • University of Westminster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males & Females (18-40 years of age)
• Healthy subjects

Exclusion Criteria:

• <18 years or >40 years
• Dieters
• Consumption of >21 serving of alcohol/week
• Any allergies/health issues related to items being ingested
• Any serious illnesses or those on medication
• Any pregnant or lactating women
• Any women who are trying to conceive
• Any women taking contraceptive medication
• Any gastrointestinal disorders
• Any chronic menstrual disorders
• Any subjects who have undergone the menopause or undergoing the perimenopause transition
• Any eating disorders
• Any depression/mental disorders
• Any abnormal blood pressure levels
• Those with deficient/excess/abnormal iron levels according to United Kingdom (UK) guidelines &/or haemochromatosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FS65_Curc; Ferrous Sulphate (65 mg/day elemental iron) and Curcumin 500 mg/day	Dietary supplement: Ferrous Sulphate 65 mg; Oral ferrous salt supplement Ferrous Sulphate 200 mg (equiv. 65 mg elemental iron content) Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach) At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules; Other Names: Ferrous Sulfate; Dietary supplement: Curcumin; HydroCurc™ 500 mg formulated curcumin At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach); Other Names: Turmeric; Curcuma longa
Placebo Comparator: FS65_Plac; Ferrous Sulphate (65 mg/day elemental iron) and Placebo (Curcumin placebo [cellulose])	Dietary supplement: Ferrous Sulphate 65 mg; Oral ferrous salt supplement Ferrous Sulphate 200 mg (equiv. 65 mg elemental iron content) Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach) At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules; Other Names: Ferrous Sulfate; Other: Placebo (Curcumin); Microcrystalline cellulose Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach)
Placebo Comparator: FS0_Plac; Placebo (Ferrous Sulphate placebo [cellulose]) and Placebo (Curcumin placebo [cellulose])	Other: Placebo (Curcumin); Microcrystalline cellulose Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach); Other: Placebo (Ferrous Sulphate); Microcrystalline cellulose Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach)
Placebo Comparator: FS18_Plac; Ferrous Sulphate (18 mg/day elemental iron) and Placebo (Curcumin placebo [cellulose])	Other: Placebo (Curcumin); Microcrystalline cellulose Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach); Dietary supplement: Ferrous Sulphate 18mg; Oral ferrous salt supplement Ferrous Sulphate 55 mg (equiv. 18 mg elemental iron content) Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach) At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules; Other Names: Ferrous Sulfate
Active Comparator: FS18_Curc; Ferrous Sulphate (18 mg/day elemental iron) and Curcumin 500 mg/day	Dietary supplement: Curcumin; HydroCurc™ 500 mg formulated curcumin At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach); Other Names: Turmeric; Curcuma longa; Dietary supplement: Ferrous Sulphate 18mg; Oral ferrous salt supplement Ferrous Sulphate 55 mg (equiv. 18 mg elemental iron content) Participants instructed to swallow opaque capsules with water away from meals (on an empty stomach) At the mid-point visit day (day 21) and the finally at the end-point (day 42) compliance will be verified by counting capsules; Other Names: Ferrous Sulfate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated inflammation	Marker: Interleukin 6 (pg/mL), Interleukin 10 (pg/mL), Interleukin 1 beta (pg/mL)	Change in Interleukin 6, Interleukin 10 and Interleukin 1 beta (ELISA) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated inflammation	Tumour Necrosis Factor alpha (pg/mL)	Change in Tumour Necrosis Factor alpha (ELISA) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated inflammation	Marker: C-Reactive Protein (g/L)	Change in C-Reactive Protein (immunoassay) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated lipid peroxidation	Marker: thiobarbituric acid reactive substances (μM)	Change in thiobarbituric acid reactive substances (ELISA) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated acute iron absorption	Marker: serum iron (μmol/L)	Change in serum iron (colorimetric analyser) from 0 and 180 minutes following supplementation
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated acute iron absorption	Marker: total iron binding capacity (μmol/L)	Change in total iron binding capacity (colorimetric analyser) from 0 and 180 minutes following supplementation
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status	Marker: serum iron (μmol/L)	Change in serum iron (colorimetric analyser) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status	Marker: total iron binding capacity (μmol/L)	Change in total iron binding capacity (colorimetric analyser) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status	Marker: Ferritin (ng/mL)	Change in ferritin (immunoassay) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status	Marker: Haemoglobin (g/dL)	Change in haemoglobin (whole blood analyser) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated iron status	Marker: Red blood cells (M/μL)	Change in red blood cells (whole blood analyser) from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated neurotrophic levels	Marker: Brain derived neurotrophic factor (BDNF) (ng/mL)	Change in BDNF (ELISA) from baseline to endpoint from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated gastrointestinal effects	Subjective analysis including: Oral Iron Supplement Questionnaire	Change in reported subjective gastrointestinal effects from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated perception of fatigue	Subjective analysis including: Visual Analogue Scale for Fatigue (VAS-F). Scores range from 0 to 100 (the higher the score the greater the level of fatigue)	Change in VAS-F from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)
To assess the influence of HydroCurc™ administration on ferrous iron supplementation associated perception of fatigue	Subjective analysis including: Fatigue Severity Scale (FSS). The total score of all answers indicates level of fatigue (a total score above ≥ 36 indicates fatigue).	Change in FSS from day 1 compared to day 21 (baseline to midpoint), day 1 compared to day 42 (baseline to endpoint) and day 21 compared to day 42 (midpoint to endpoint)

Collaborators and Investigators

• Sponsor: University of Westminster
• Collaborators: Gencor Pacific Group

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2018
• Primary Completion (Actual): November 11, 2019
• Study Completion (Actual): January 31, 2020

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Actual): July 10, 2020
• Last Update Submitted That Met QC Criteria: July 6, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: fatigue; supplement; ferrous sulphate; curcumin; iron; gastrointestinal; turmeric; nutraceutical; inflammatory status; anti-oxidant; oxidative status; Hydrocurc
• 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; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Curcumin
• Other Study ID Numbers: ETH1718-0907

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