Effect of Weight Loss on Hepcidin Levels and Iron Status in Subjects With Obesity.

NCT06104800 | Completed DMC

• 1 other identifier: FNU-4686-23-24-1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity and iron deficiency are the nutritional disorders with the highest prevalence worldwide. Different mechanisms have been proposed to explain iron deficiency secondary to obesity. Among the most studied is the deficit in dietary iron intake or the increase in blood volume that increases the need for the metal. However, one of the most plausible mechanisms linking obesity and iron deficiency is low-grade systemic inflammation, through the iron metabolism intermediate known as hepcidin. The investigators objective is to evaluate the effect of weight loss by caloric restriction on hepcidin and serum iron concentration in people living with obesity and iron deficiency. The study will be divided into two phases: Phase 1: A cross-sectional study (cases and controls) to compare hepcidin levels, iron status and inflammatory markers in people living with and without obesity. The second phase consists of an open-label randomized controlled clinical trial. Individuals living with obesity who are iron deficient will be recruited and randomized to one of 2 dietary intervention groups with 60-day follow-up. The intervention groups will be: diet with caloric restriction rich in protein (with red meat) and diet with caloric restriction rich in protein (without red meat). Hepcidin levels, iron status and inflammatory markers will be determined at the beginning and end of the intervention. The nutritional intervention will have the following distribution of macronutrients in the diet: protein 1.5 g/kg of ideal weight, 50% carbohydrates and 25-30% fats.

Conditions

Obesity; Iron Deficiency Anemia

Outcome Measures

Primary Outcomes (2)

• Serum iron concentration in mcg/dL

  Change in serum iron concentration between different nutritional interventions in subjects with obesity and iron deficiency

  Baseline to 2 months of intervention

• Serum hepcidin concentration in mcg/dL

  Change in serum hepcidin concentration between different nutritional interventions in subjects with obesity and iron deficiency

  Baseline to 2 months of intervention

Secondary Outcomes (23)

• Serum ferritin concentration in ng/mL

  Baseline to 2 months of intervention

• Serum iron binding capacity concentration in mcg/dL

  Baseline to 2 months of intervention

• Blood reticulocytes percentage

  Baseline to 2 months of intervention

• Serum soluble transferrin receptor concentration in mg/L.

  Baseline to 2 months of intervention

• Blood haemoglobin concentration in g/dL

  Baseline to 2 months of intervention

Study Arms (2)

Red meat diet

EXPERIMENTAL

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (including red meat), 50% carbohydrates, and 25-30% fats.

Other: Calorie-restricted diet with red meat

Red meat free diet

ACTIVE COMPARATOR

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (excluding red meat), 50% carbohydrates, and 25-30% fats

Other: Calorie-restricted diet without red meat

Interventions

Calorie-restricted diet with red meat OTHER

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (including red meat), 50% carbohydrates, and 25-30% fats.

Red meat diet

Calorie-restricted diet without red meat OTHER

Calorie-restricted diet with macronutrient distribution: 1.5 g/kg of ideal body weight in protein (excluding red meat), 50% carbohydrates, and 25-30% fats

Red meat free diet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1
• Signing of the informed consent form
• Both sexes
• Adults over 18 years of age
• BMI of 18.5 and under 40 kg/m2
• Phase 2
• Both sexes
• Adults older than 18 years
• People with obesity (BMI of 30 to 40 kg/m2) and serum iron \< 50 micrograms/dL.
• Total cholesterol less than 240 mg/dL (with the diet plan 20% decrease).

You may not qualify if:

• Any type of diabetes.
• Patients with renal disease diagnosed by a physician.
• Patients with acquired diseases that secondarily produce obesity and diabetes.
• Patients who have suffered a cardiovascular event.
• Weight loss \> 3 kg in the last 3 months.
• Patients with catabolic diseases such as cancer and acquired immunodeficiency syndrome.
• Pregnancy.
• Treatment with any drug treatment:
• Treatment with antihypertensive drugs (loop or potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers, alpha blockers, calcium antagonists, beta blockers).
• Treatment with hypoglycemic agents (sulfonylureas, biguanides, incretins) or insulin and antidiabetics.
• Treatment with statins, fibrates or other drugs to control dyslipidemia.
• Use of steroid drugs, chemotherapy, immunosuppressants or radiotherapy.
• Anorectics or drugs that accelerate weight loss.
• Any drug or medication that activates intestinal motility (cisapride, dimethicone, domperidone, metoclopramide, trimebutine).
• Laxatives or antispasmodics 4 weeks prior to the study h) Antibiotic treatment 2 months prior to the study.

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead

Study Sites (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

México, Mexico

Location

Related Publications (22)

• Zhou Z, Zhang H, Chen K, Liu C. Iron status and obesity-related traits: A two-sample bidirectional Mendelian randomization study. Front Endocrinol (Lausanne). 2023 Feb 14;14:985338. doi: 10.3389/fendo.2023.985338. eCollection 2023.

  PMID: 36864839 BACKGROUND

• Yanoff LB, Menzie CM, Denkinger B, Sebring NG, McHugh T, Remaley AT, Yanovski JA. Inflammation and iron deficiency in the hypoferremia of obesity. Int J Obes (Lond). 2007 Sep;31(9):1412-9. doi: 10.1038/sj.ijo.0803625. Epub 2007 Apr 17.

  PMID: 17438557 BACKGROUND

• Becker C, Schumann K. Iron-homeostasis and obesity. J Trace Elem Med Biol. 2015 Apr;30:194. doi: 10.1016/j.jtemb.2014.06.009. Epub 2014 Jun 27. No abstract available.

  PMID: 25023846 BACKGROUND

• Coimbra S, Catarino C, Santos-Silva A. The role of adipocytes in the modulation of iron metabolism in obesity. Obes Rev. 2013 Oct;14(10):771-9. doi: 10.1111/obr.12057. Epub 2013 Jul 11.

  PMID: 23841713 BACKGROUND

• Collins JF, Wessling-Resnick M, Knutson MD. Hepcidin regulation of iron transport. J Nutr. 2008 Nov;138(11):2284-8. doi: 10.3945/jn.108.096347.

  PMID: 18936232 BACKGROUND

• Anderson GJ, Frazer DM. Current understanding of iron homeostasis. Am J Clin Nutr. 2017 Dec;106(Suppl 6):1559S-1566S. doi: 10.3945/ajcn.117.155804. Epub 2017 Oct 25.

  PMID: 29070551 BACKGROUND

• Ross AC. Impact of chronic and acute inflammation on extra- and intracellular iron homeostasis. Am J Clin Nutr. 2017 Dec;106(Suppl 6):1581S-1587S. doi: 10.3945/ajcn.117.155838. Epub 2017 Oct 25.

  PMID: 29070546 BACKGROUND

• Joffin N, Gliniak CM, Funcke JB, Paschoal VA, Crewe C, Chen S, Gordillo R, Kusminski CM, Oh DY, Geldenhuys WJ, Scherer PE. Adipose tissue macrophages exert systemic metabolic control by manipulating local iron concentrations. Nat Metab. 2022 Nov;4(11):1474-1494. doi: 10.1038/s42255-022-00664-z. Epub 2022 Nov 3.

  PMID: 36329217 BACKGROUND

• Gabrielsen JS, Gao Y, Simcox JA, Huang J, Thorup D, Jones D, Cooksey RC, Gabrielsen D, Adams TD, Hunt SC, Hopkins PN, Cefalu WT, McClain DA. Adipocyte iron regulates adiponectin and insulin sensitivity. J Clin Invest. 2012 Oct;122(10):3529-40. doi: 10.1172/JCI44421. Epub 2012 Sep 10.

  PMID: 22996660 BACKGROUND

• Moreto F, de Oliveira EP, Manda RM, Burini RC. The higher plasma malondialdehyde concentrations are determined by metabolic syndrome-related glucolipotoxicity. Oxid Med Cell Longev. 2014;2014:505368. doi: 10.1155/2014/505368. Epub 2014 Jun 24.

  PMID: 25089170 BACKGROUND

• Nikonorov AA, Skalnaya MG, Tinkov AA, Skalny AV. Mutual interaction between iron homeostasis and obesity pathogenesis. J Trace Elem Med Biol. 2015 Apr;30:207-14. doi: 10.1016/j.jtemb.2014.05.005. Epub 2014 May 24.

  PMID: 24916791 BACKGROUND

• Teng IC, Tseng SH, Aulia B, Shih CK, Bai CH, Chang JS. Can diet-induced weight loss improve iron homoeostasis in patients with obesity: A systematic review and meta-analysis. Obes Rev. 2020 Dec;21(12):e13080. doi: 10.1111/obr.13080. Epub 2020 Jul 16.

  PMID: 32677171 BACKGROUND

• Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci. 2014 Feb;19(2):164-74.

  PMID: 24778671 BACKGROUND

• Dev S, Babitt JL. Overview of iron metabolism in health and disease. Hemodial Int. 2017 Jun;21 Suppl 1(Suppl 1):S6-S20. doi: 10.1111/hdi.12542. Epub 2017 Mar 15.

  PMID: 28296010 BACKGROUND

• Zhang C, Rawal S. Dietary iron intake, iron status, and gestational diabetes. Am J Clin Nutr. 2017 Dec;106(Suppl 6):1672S-1680S. doi: 10.3945/ajcn.117.156034. Epub 2017 Oct 25.

  PMID: 29070554 BACKGROUND

• Frazer DM, Wilkins SJ, Becker EM, Vulpe CD, McKie AT, Trinder D, Anderson GJ. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology. 2002 Sep;123(3):835-44. doi: 10.1053/gast.2002.35353.

  PMID: 12198710 BACKGROUND

• Cao C, Thomas CE, Insogna KL, O'Brien KO. Duodenal absorption and tissue utilization of dietary heme and nonheme iron differ in rats. J Nutr. 2014 Nov;144(11):1710-7. doi: 10.3945/jn.114.197939. Epub 2014 Sep 10.

  PMID: 25332470 BACKGROUND

• Chiabrando D, Vinchi F, Fiorito V, Mercurio S, Tolosano E. Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes. Front Pharmacol. 2014 Apr 8;5:61. doi: 10.3389/fphar.2014.00061. eCollection 2014.

  PMID: 24782769 BACKGROUND

• Vela D. Hepcidin, an emerging and important player in brain iron homeostasis. J Transl Med. 2018 Feb 7;16(1):25. doi: 10.1186/s12967-018-1399-5.

  PMID: 29415739 BACKGROUND

• Amato MC, Giordano C. Visceral adiposity index: an indicator of adipose tissue dysfunction. Int J Endocrinol. 2014;2014:730827. doi: 10.1155/2014/730827. Epub 2014 Apr 14.

  PMID: 24829577 BACKGROUND

• Utami FA , Lee HC , Su CT , Guo YR , Tung YT , Huang SY . Effects of calorie restriction plus fish oil supplementation on abnormal metabolic characteristics and the iron status of middle-aged obese women. Food Funct. 2018 Feb 21;9(2):1152-1162. doi: 10.1039/c7fo01787a.

  PMID: 29362766 BACKGROUND

• Mejia-Rodriguez F, Villalpando S, Shamah-Levy T, Garcia-Guerra A, Mendez-Gomez Humaran I, De la Cruz-Gongora VV. Prevalence of iron deficiency was stable and anemia increased during 12 years (2006-2018) in Mexican women 20-49 years of age. Salud Publica Mex. 2021 May 3;63(3 May-Jun):401-411. doi: 10.21149/12152. Spanish.

  PMID: 34098613 BACKGROUND

MeSH Terms

Conditions

Obesity; Anemia, Iron-Deficiency

Interventions

Caloric Restriction; Red Meat

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Meat; Food; Food and Beverages

Study Officials

• Martha Guevara-Cruz, MD, PhD

  Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The person who will perform the biochemical determinations and the statistical analysis will be blinded from the intervention group by assigning each patient.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The groups will receive the treatment simultaneously.

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: October 27, 2023
• Study Start: January 8, 2024
• Primary Completion: April 30, 2024
• Study Completion: January 24, 2025
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)