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reference
Tiekou Lorinczova H, Begum G, Temouri L, Renshaw D, Zariwala MG. Co-administration of iron and bioavailable curcumin reduced levels of systemic markers of inflammation and oxidative stress in a placebo-controlled, randomized trial.Nutrients. 2022;14(3):712.
Study objective
To determine whether coadministration of iron (ferrous sulfate) with a bioavailable form of curcumin reduces systemic inflammation and/or gastrointestinal (GI) side effects
Key to take away
High doses of iron can lead to darker stools and curcumin can counteract this known effect.
design
Double-blind, placebo-controlled, randomized study
Participant
The researchers recruited participants who were generally healthy and whose ferritin levels were within the normal range (>15 ng/ml). They recruited 155 healthy participants (79 men, 26.42 years ± 0.55; and 76 women, 25.82 years ± 0.54).
Participant ethnicity includes: Caucasian 64.3%, Asian 22.1%, African 3.2%, Central or South American 2.6%, and other 7.8%.
Researchers excluded people with low hemoglobin, known medical conditions, taking supplements or medications, excessive alcohol consumption, or with chronic gastrointestinal symptoms, eating disorders, mental illness, or hypo-/hypertensive blood pressure measurements. One participant was excluded from data analysis due to a high body mass index (>40 kg/m ).2).
Interventions
The process consisted of 5 parts:
- Eisen-Placebo und Curcumin-Placebo
- Niedrig dosiertes (18 mg) Eisen- und Curcumin-Placebo
- Niedrig dosiertes Eisen und Curcumin
- Hochdosiertes (65 mg) Eisen- und Curcumin-Placebo
- Hochdosiertes Eisen und Curcumin
The researchers used ferrous sulfate as a form of iron and administered curcumin (HydroCurc) at a dosage of 500 mg/day. Instructions included conducting the intervention at least 1 hour before or 2 hours after consuming food. The study duration was 6 weeks.
Evaluated study parameters
Biochemical assessment included hemoglobin, serum ferritin, C-reactive protein (CRP), serum iron (Fe), total iron binding capacity (TIBC), transferrin saturation (TS) and unsaturated iron binding capacity (UIBC), interleukin 6 (IL). -6), interleukin 10 (IL-10), interleukin 1 beta (IL-1b), tumor necrosis factor (TNF) and thiobarbituric acid-reactive substances (TBARS).
Subjective assessment included the Fatigue Severity Scale (FSS), the Fatigue Visual Analog Scale (F-VAS), and the questionnaire assessing gastrointestinal symptoms after oral iron supplementation, as well as a question related to dark or black stools.
Assessments were conducted at baseline, midpoint, and endpoint, and participants completed the GI questionnaire online daily.
Primary outcome
The primary endpoints were markers of systemic inflammation: IL-1, IL-6, TNF and TBARS. All other measurements, both subjective and objective, were secondary.
Key findings
There was a significant reduction in mean plasma TNF levels (0.65 pg/ml ± 0.17).P=0.0018) when comparing the mean values with the mean endpoint values in the high-dose iron and curcumin arm. Also a significant reduction in mean plasma TNF (0.35 pg/ml ± 0.13,P=0.0288) occurred in the low-dose iron and curcumin arm and in the high-dose iron and placebo arm (0.39 pg/ml ± 0.15, P=0.0363).
When comparing the double placebo group with the group taking 65 mg iron and a curcumin placebo, there was a significant association with darker stools (P=0.002, Fisher exact test).
Finally, when comparing the mean to the endpoint, there was a significant reduction in IL-6 in the group taking high-dose iron plus curcumin (0.06 pg/ml ± 0.02, P=0.0073).
transparency
The financier,Gencor Pacific Ltd.,Whoever makes HydroCurc was involved in the study design process but not in data collection or analysis. The authors declare no other conflict of interest.
Implications and limitations for practice
Examination of healthy subjects plays a role in determining the safety of interventions as well as detecting subtle changes. However, this can make it more difficult to detect changes. One technique the researchers used involved conducting a subgroup analysis of participants with low ferritin levels, either below 30 ng/ml or below 50 ng/ml. The reason for these limits is to achieve higher sensitivity than the World Health Organization recommendation of 15 ng/ml.3-4Values below 50 ng/ml may result in reduced bone marrow stores or latent iron deficiency.5This can be referred to as iron deficiency without anemia or colloquially as suboptimal levels.
From a practical perspective, this study has significant limitations as it recruits young, healthy and non-obese participants with normal iron status. In clinical practice, higher-dose iron supplementation without objective need is rare. Essentially, the researchers wanted to identify effects on inflammation in patients who show no obvious signs or symptoms of inflammation.
One of the most common objective markers of inflammation in clinical practice is C-reactive protein, an acute phase protein produced by the liver. CRP increases in relation to IL-6 and is often elevated due to systemic inflammation or infection.6However, no statistically significant change in CRP was observed between any of the study arms in this study. The marker may not be sensitive enough if the inflammatory cascade is already normal in a healthy population.
However, changes in plasma IL-6 were observed in the high-dose iron and curcumin arm (P=0.0073) in the subgroup analysis of people with ferritin levels above 30 ng/ml. Similar effects were observed with circulating TNF. IL-1b and IL-10 were not affected by the procedure. While these cytokines and inflammatory indicators are useful in research, they are not often assessed in clinical practice.
Serum iron levels, which are routinely measured in practice, remained unchanged during this procedure; This is not surprising given the population studied. However, ferritin levels were affected in both the curcumin-placebo arm and the curcumin-active arm, although in an inconsistent manner. Ferritin increased more significantly in the high-dose iron and curcumin and placebo arm than in the high-dose iron and curcumin arm. This may lead the reader to believe that bioavailable curcumin may inhibit iron absorption or storage; However, in the low-dose iron arms and the low normal ferritin analysis (>30 ng/mL), the active curcumin arm responded more strongly than the placebo arm. Furthermore, a previous study using the same material failed to detect any inhibitory effect.7
From a practical application perspective, this study has significant limitations as it recruits young, healthy and non-obese participants with normal iron status.”
Subjective fatigue ratings did not differ significantly between arms throughout the study. Perhaps the most compelling and clinically useful consideration of this study was the change in darker stool. For patients who require a higher dose or longer duration of treatment or who report darker stools with lower iron doses, bioavailable curcumin appears to be a promising adjunct recommendation.
Since iron supplementation can cause pro-inflammatory side effects, the use of a recognized anti-inflammatory measure makes sense. The curcumin used in this study was HydroCurc, which is described as a bioavailable curcumin product containing 85% curcuminoids. The delivery system is patented and may contain processes or materials that are objectionable to some patients and/or physicians. Several attempts to improve the pharmacokinetic profile of curcumin and its precursor turmeric have been commercialized. Some questions that remain following this study include whether other curcumin products have the same or similar effects, whether the dose used in this study is most appropriate, and whether the duration of the study is long enough to detect clinically relevant effects.
Disclosure of Conflicts of Interest
The author is employed by a company that sells turmeric products, but not the product that is the subject of this study, and otherwise declares no conflict of interest.
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