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Effect of Polyphenols on Absorption of Iron From Sodium Iron Chlorophyllin

Evaluating the Effect of Polyphenols on the Iron Bioavailability From Iron Chlorophyllin in Young Women Using the Iron Stable Isotopic Method

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04849832
Acronym
polySIC
Enrollment
40
Registered
2021-04-19
Start date
2021-06-21
Completion date
2021-07-26
Last updated
2021-11-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Iron-deficiency

Brief summary

Polyphenols present in tea are known to inhibit the absorption of non heme iron. The inhibiting effect of tea on non-heme iron absorption is attributed to the flavonoids present in tea. It is well known that Ferrous sulfate is not absorbed well in the presence of polyphenols. We would like to evaluate the effect of polyphenols on the newly developed compound, sodium iron chlorophyllin (SIC), which mimics the heme iron structure. Comparisons of fractional absorption of SIC and Ferrous Sulfate in the presence of polyphenols can help identify the performance of the compounds as vehicles for iron delivery in the presence of iron absorption inhibitors. In a single-blind randomized cross-over study using stable iron isotope technique, iron bioavailability from SIC delivered with an inhibitory matrix can therefore be determined when given along with black tea

Detailed description

New approaches to treat iron deficiency include developing novel iron compounds with possible iron absorption routes that increase iron bioavailability and reduce gastrointestinal side effects. Sodium iron chlorophyllin (SIC) is a water-soluble semisynthetic chlorophyll derivative where the magnesium in the porphyrin ring has been substituted by iron. Given the porphyrin ring heme-like structure of SIC, it may be an alternative delivery route for iron, suitable also for vegetarians and vegans. Yet, there are few studies investigating the use of SIC for this purpose. We recently completed the study entitled Evaluation of iron bioavailability from iron chlorophyllin in young women using the iron stable isotopic method based on previous in vitro and in vivo studies.. The study showed a 7% fractional iron absorption (FIA) from SIC when compared to the control compound, ferrous sulfate, which had a FIA of 30%, indicating a Relative Bioavailability of SIC of 20%. The study showed an inverse relationship between ferritin status and iron absorption from SIC in the study participants and an increase in the FIA in the presence of ascorbic acid. Both these findings lean towards the possibility that that the iron contributing to the FIA from SIC may be iron that was dissociated from the porphyrin ring of the chlorophyllin and entering the common non heme iron pool. This inverse relationship in ferritin and FIA is well known for ferrous sulfate. However, one cannot confirm the pathway taken up by SIC to deliver iron based on the previous study alone. Polyphenols present in tea are known to inhibit the absorption of non heme iron.The inhibiting effect of tea on non-heme iron absorption is attributed to the flavonoids present in tea. There are several types of tea flavonoids: monomers (catechin), dimers (theaflavin), and polymers (thearubigin). Black tea contains 10% flavanols, 25% catechins, 20% theaflavins and 45% thearubigins. The mechanism of iron absorption inhibition by tea is by formation of a complex of the flavonoids with iron. It is mainly the galloyl group in these phenolic compounds that specifically binds iron. A cup of black tea, brewed with 2.5 g tea leaves contains about 200 mg tea flavonoids . Heme iron absorption has also been shown to be inhibited by the presence of polyphenols but unclear to what extent. Thus, comparisons of fractional absorption of SIC and Ferrous Sulfate in the presence of polyphenols can help identify the performance of the compounds as vehicles for iron delivery in the presence of iron absorption inhibitors. In a single-blind randomized cross-over study using stable iron isotope technique, iron bioavailability from SIC delivered with an inhibitory matrix can therefore be determined when given along with black tea. SIC has been produced at the HNL with a 50% incorporation of iron into the chlorophyll. Our protocol is based on a Unilever patent that is no longer active, with in-house adaptation. The SIC has a neutral taste and will be presented as a dark green liquid, being the solution of SIC in water. If SIC, as hypothesized, behaves in a similar way to heme, then iron absorption inhibitors, such as the polyphenols, will not have an effect on the absorption of iron from SIC.

Interventions

DIETARY_SUPPLEMENTSIC + tea

Sodium Iron Chlorophyllin as prepared by the human nutrition laboratory, ETH Zurich with 2g of tea brewed for 5 minutes

DIETARY_SUPPLEMENTFeSO4

Ferrous sulfate solution serves as a positive control - and whose absorption is well known.

DIETARY_SUPPLEMENTSIC

Sodium Iron Chlorophyllin as prepared by the human nutrition laboratory, ETH Zurich

DIETARY_SUPPLEMENTFeSO4 + tea

Ferrous sulfate solution given with 2g of tea brewed for 5 minutes - expected iron absorption inhibition

Sponsors

Swiss Federal Institute of Technology
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Masking description

There will be no masking as the ferrous sulfate solutions will be colourless compared to the green color solution of SIC

Intervention model description

The study will be a randomized, single centre cross over study where every participant will receive all the four interventions.

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes

Inclusion criteria

* female aged between 18-45 y old; * SF \<80 µg/L; * BMI 18.5-24.9 kg/m2; * weight \<70 kg; * signed informed consent; * able to communicate and comprehend English language.

Exclusion criteria

* anemia (Hb \<12 g/dL); * Inflammation (CRP \> 5 mg/L); * chronic digestive, renal and/or metabolic disease; * chronic medications (except for oral contraceptives); * use of vitamin, mineral and pre- and/or probiotic supplements in the previous 2 weeks before study initiation and during the course of the study; * blood transfusion, blood donation or significant blood loss over the past 4 months; * difficulties with blood sampling; * antibiotic treatment in the 4 weeks before study initiation; * pregnancy (tested in serum at screening) or intention to become pregnant; * lactation up to 6 weeks before study initiation; * earlier participation in a study using stable isotopes or participation in any clinical study within the last 30 days; * unable to comply with study protocol (e.g. not available on certain study appointment days or difficulties with blood withdrawal); * inability to understand the information sheet and the informed consent form due to cognitive or language reasons; * smoking; * unwilling to use an effective method of contraception.

Design outcomes

Primary

MeasureTime frameDescription
Ratio of FIA of SIC arms vs ratio of FIA of Ferrous sulfate armsDay 1 of the studyratio of iron bioavailability (as measured by erythrocyte incorporation of the stable isotope labels) from SIC in a polyphenol matrix to that from SIC alone with the ratio of iron bioavailability from FeSO4 in a polyphenol matrix to that from FeSO4 alone.

Secondary

MeasureTime frameDescription
Hemoglobinday 1, day 17 and day 33 of the the studyIron status biomarker
Ferritinday 1, day 17 and day 33 of the the studyIron status biomarker
sTfRday 1, day 17 and day 33 of the the studyIron status biomarker
C-reactive Proteinday 1, day 17 and day 33 of the the studyInflammation marker

Countries

Switzerland

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026