Effects of Gum Arabic on Metabolic Syndrome Parameters in Postmenopausal Women

Phase 2

• Conditions: Metabolic Syndrome in Postmenopausal Females
• Interventions: Drug: Gum Arabic

• Registration Number: NCT04978103
• Lead Sponsor: University of Khartoum

Brief Summary

Gum Arabic ingestion has been proved to decrease some of the inflammatory markers in some metabolic diseases that have an inflammatory background. Nevertheless, the mechanism/s by which it does so is uncertain. This study is targeting one of the postulated molecular mechanisms at genetic level that may help to understand how Gum Arabic exerts its effect .The effects of GA on Nuclear Factor Kappa Beta, P38 Mitogen Activated Protein (MAP) Kinase levels, and on the expression of inflammatory cytokines genes are going to be assessed in postmenopausal females with Metabolic Syndrome.

Detailed Description

The Metabolic syndrome (MetS) is a collection of several interconnected biochemical, clinical, and metabolic factors that directly increase the risk of atherosclerotic cardiovascular disease and Diabetes Mellitus.

Hypertension, Dyslipidemia, insulin resistance, obesity, glucose intolerance, proinflammatory and prothrombotic states are the cornerstone features defining the syndrome. Glycerol, free fatty acids (FFA), tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), interleukin 1(IL-1) and Interferon Gamma (INFγ) are some of the inflammatory substances (cytokines) that are released from different cells (monocytes and adipocytes) in MetS.

Gum Arabic is found as a mixture of sodium, calcium and potassium salts of branched polysaccharides. In the colon, GA is fermented by colonic bacteria into short chain fatty acids such as butyrate, which are partially absorbed into blood.

Butyrate treatment was found to inhibit expression of cytokine mRNAs in peripheral blood monocytes (PBMC) that are stimulated by bacterial lipopolysaccharide (LPS).

In unstimulated (PBMC), a transcription factor (Nuclear Factor kappa β (NF-κB)) controls gene expression of some inflammatory cytokines; Tumor Necrosis Factor Alpha (TNF- α), IL-1 and IL-6. NF-κB was detected mainly in the cytoplasm tightly bound to an Inhibitory protein (IκB).

When those cells are stimulated by bacterial lipopolysaccharide (LPS) or by adipokines, NFκB is activated and translocates to the nucleus to start gene expression of the inflammatory cytokines. Moreover; stimulation causes degradation of IκB which releases NFκB and allows its translocation to the nucleus.

This nuclear translocation of NFκB was found to be inhibited by butyrate (a byproduct of Gum Arabic fermentation ) providing evidence that butyrate mediated reduction of proinflammatory cytokines was achieved by reducing NFκB activation.

Consequently; the postulated mechanisms by which butyrate may regulate gene expression are through inhibition of NFκB activation and IκBα degradation.

NFκB and the inflammatory cytokines: Target for therapy in inflammatory diseases, are they?

As NFκB is involved in transcriptional regulation of many cytokines genes that contributes to immune and inflammatory responses, it may be a good target for therapy also. At present, treatment of inflammatory diseases depends greatly on aminosalicylates, corticosteroids, and immune-suppressants that decrease cytokines level especially TNF.

The anti-inflammatory and immune-modulatory properties of gum Arabic, through butyrate, described previously may offer an interesting alternative therapeutic approach for inflammatory conditions.

Study Timeline

• Study Start: 2019-12-04
• Primary Completion: 2021-01-10
• Status Verified: 2021-07
• Study First Submitted: 2021-07-10
• Study First Submitted QC: 2021-07-15
• Study First Posted: 2021-07-27
• Last Update Submitted: 2021-07-27
• Last Update Posted: 2021-08-03
• Study Completion: 2022-12-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 100

Inclusion Criteria

• Inclusion criteria Females Menopause Metabolic syndrome based on Adult panel II criteria Signed/verbal consent to participate

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Exclusion Criteria

• Exclusion criteria

  1. Patients with mental or physical disability
  2. Use of corticosteroids or any other drug that affects body weight
  3. History of Gum Arabic (GA) allergy
  4. Chronicrenal or liver disease
  5. Chronocinflammatory diseases
  6. History of CVA or MI Participants will be asked to maintain their habitually daily diet and level of activity during the period of the study and to continue any previously prescribed medication.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	Gum Arabic	Hundred postmenopausal women were enrolled and received therapeutic dose of Gum Arabic (0.5 gm/kg/day) and followed for 12 weeks then the intended outcomes will be compared before and after completion of the study

Primary Outcome Measures

Name	Time	Method
Fasting Insulin in nanogram/dl	12 weeks	Metabolic hormone
Insulin resistance by HOMA index	12 weeks	Measuring cells sensitivity to insulin
Nuclear Factor Kappa Beta concentration in nanogram/dl	12 weeks	Nuclear regulatory protein
P38 Mitogen activated protein kinase in nanogram/dl	12 weeks	Transcription regulatory protein
Inhibitory Kappa Beta protein in nanogram/dl	12 weeks	inhibitory protein
Plasminogen activated protein inhibitor1 in picogram/dl	12 weeks	Protein Inhibitor
Tumor necrosis factor, interferon gamma and interleukin-6 in nanogram/dl	12 weeks	Proinflammatory cytokines

Secondary Outcome Measures

Name	Time	Method
Fasting Blood Sugar in mg/dl	12 weeks	Biochemical serological markers
Lipid profile in mg/dl	12 weeks	Serological markers

Trial Locations

Locations (1)

University of Khartoum; 🇸🇩 Khartoum, Sudan