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Completed

NCT Number: NCT06377631

Effect of Multi-ingredient on Visceral Adiposity & Non-alcoholic Fatty Liver Disease in Postmenopausal Women With Abdominal Obesity

This study aims to evaluate the effect of daily intake of a specific combination of different natural histidine-related amino acids in combination with dietary recommendations, in the reduction of visceral fat, as well as their associated comorbidities, in postmenopausal women with abdominal obesity.

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Key information

Conditions

Visceral Obesity Body Weight Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Non-alcoholic Fatty Liver Disease Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity, Abdominal Overnutrition Overweight Pathological Conditions, Signs and Symptoms Postmenopausal Signs and Symptoms

Age range

50 year–65 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Anna Crescenti, Reus, Catalonia. Spain, Spain

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About this study

In postmenopausal women, the risk of non-alcoholic fatty liver disease (NAFLD) increases due to hormonal changes and metabolic shifts. Menopause leads to a decline in estrogen levels, affecting lipid metabolism and promoting abdominal and visceral fat accumulation. This visceral adiposity poses a significant risk factor for insulin resistance, type 2 diabetes, dyslipidemia, cardiovascular diseases, and NAFLD. While the prevalence of NAFLD is initially higher in men, it becomes comparable or even higher in postmenopausal women due to these metabolic changes.

Studies suggest that estrogen deficiency post-menopause contributes to the development of NAFLD in women. Lower serum estrogen levels are associated with a higher likelihood of NAFLD development, indicating the potential role of hormone replacement therapy (HRT) in mitigating NAFLD risk in postmenopausal women. However, the use of HRT must be carefully evaluated due to potential adverse effects on cardiovascular health.

Thus, novel, effective and safety therapeutic strategies for managing metabolic disorders in postmenopausal women are highly desirable.

The main objective of this study is to evaluate the effect of daily intake of a specific combination of different natural histidine-related amino acids in combination with dietary recommendations, in the reduction of visceral fat in postmenopausal women with abdominal obesity.

The secondary objectives of this study are to evaluate the effect of daily intake of the multi-ingredient aforementioned in liver function markers, anthropometric parameters, blood pressure and heart rate, markers of lipid metabolism, markers of glucidic metabolism, inflammatory markers, histidine serum levels, sexual hormones, the temperature of supraclavicular brown adipose tissue, changes in the intestinal microbiota, changes in the expression of lipid metabolism-related genes and symptoms associated with postmenopause.

A randomized, parallel, placebo-controlled, single-center, triple-blind clinical trial with a 1:1:1 ratio between interventions with 50 participants will be conducted.

During the study there will be 4 visits: a preselection visit (V0; day -7) and 3 study visits during the consumption of the treatments, which will take place on the first day of the study (V1; day 1 +/- 3 days; week 1), at 6 weeks of treatment (V2; day 43 +/- 3 day; week 6) and at 12 weeks of treatment (V3; day 85 +/- 3 days; week 12).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Postmenopausal women aged 50 to 65 years.
  • BMI ≥27.5 kg/m^2 and ≤32.5 kg/m^2.
  • Waist circumference ≥88 cm.
  • No hormone replacement therapy.
  • Read, write and speak Catalan or Spanish.
  • Sign the informed consent.

Exclusion criteria

  • Present values of body mass index < 27.5 kg/m^2 or > 32.5 kg/m^2
  • Present values of waist circumference > 115 cm.
  • Present diabetes.
  • Present dyslipidemia.
  • Present anemia.
  • Taking supplements, multivitamin supplements or phytotherapeutic products that interfere with the treatment under study.
  • Consume 2 or more Standard Beverage Units (SBU) daily or 17 SBU weekly.
  • Be a smoker.
  • Present any diagnosed liver disease other than NAFLD.
  • Have lost more than 3 kg of weight in the last 3 months.
  • Present food intolerances and/or allergies related to the study products, such as hypersensitivity to maltodextrin or N-Acetylcysteine.
  • Presenting any chronic or autoimmune disease in clinical manifestation such as hepatitis, hyper or hypothyroidism or metabolic diseases.
  • Follow a pharmacological treatment with immunosuppressants, cytotoxic agents, corticosteroids or other drugs that could cause hepatic steatosis or alter the measurements in the liver.
  • Being participating or having participated in a clinical trial or nutritional intervention study in the last 30 days before inclusion in the study.
  • Follow a hypocaloric diet and/or pharmacological treatment for weight loss.
  • Suffering from eating behavior disorders or psychiatric disorders.
  • Being unable to follow study guidelines.

Treatment and study plan

Multi-ingredient of L-histidine, L-serine, L-carnosine and N-Acetylcysteine

Dietary Supplement

The product will be presented in powder format in a single container and with a measuring spoon of the daily dose.

Placebo

Dietary Supplement

The product will be presented in powder format in a single container and with a measuring spoon of the daily dose.

Primary outcomes

  1. Change in Visceral Adiposity

    Time frame: Change from Baseline Visceral Adiposity at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Visceral fat content measured using a dual energy x-ray absorptiometry (DXA) scanner

Secondary outcomes

  1. Height (cm)

    Time frame: At baseline

    Height measured with standardized method

  2. Age

    Time frame: At day -7 (pre-selection visit)

    The age of the volunteers will be recorded in the case report form.

  3. Ethnicity

    Time frame: At day -7 (pre-selection visit)

    The ethnicity of the volunteers will be recorded in the case report form.

  4. Change in Body Weight (kg)

    Time frame: Change from Baseline Weight at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Weight measured with standardized method

  5. Change in Body Mass Index (BMI) (Kg/m^2)

    Time frame: Change from Baseline Body Mass Index at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Weight and height will be combined to report BMI in kg/m^2

  6. Change in Neck circumference (cm)

    Time frame: Change from Baseline Neck circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Neck circumference using a measuring tape

  7. Change in Arm circumference (cm)

    Time frame: Change from Baseline Arm circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Arm circumference using a measuring tape

  8. Change in Waist circumference (cm)

    Time frame: Change from Baseline Waist circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Waist circumference using a measuring tape

  9. Change in Hip circumference (cm)

    Time frame: Change from Baseline hip circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Hip circumference using a measuring tape

  10. Change in Conicity Index

    Time frame: Change from Baseline Conicity Index at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Weight, height and waist circumference will be combined to report Conicity index.

  11. Change in Waist-to-Hip ratio

    Time frame: Change from Baseline Waist-to-Hip ratio at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Waist and Hip circumference will be combined to report Waist-to-Hip ratio

  12. Change in Lipid Accumulation Product (LAP)

    Time frame: Change from Baseline Lipid Accumulation Product ratio at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Waist circumference and fasting plasma Triglycerides will be combined to report Lipid Accumulation Product

  13. Change in Systolic Blood Pressure (mm Hg)

    Time frame: Change from Baseline Systolic Blood Pressure at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Systolic blood pressure will be measured using an automatic sphygmomanometer

  14. Change in Diastolic Blood Pressure (mm Hg)

    Time frame: Change from Baseline Systolic Blood Pressure at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Diastolic blood pressure will be measured using an automatic sphygmomanometer

  15. Change in heart rate (bpm)

    Time frame: Change from Baseline Heart rate at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Heart rate will be measured using an automatic sphygmomanometer

  16. Change in serum glucose levels (mg/dL)

    Time frame: Change from Baseline serum glucose levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Serum glucose levels will be determined by standardized spectrophotometry methods

  17. Change in serum total cholesterol (mg/dL)

    Time frame: Change from Baseline serum total cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Total cholesterol will be determined by standardized spectrophotometry methods

  18. Change in serum high-density lipoprotein cholesterol (HDL-C,mg/dL)

    Time frame: Change from Baseline serum high-density lipoprotein cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    High-density lipoprotein cholesterol will be determined by standardized spectrophotometry methods

  19. Change in serum low-density lipoprotein cholesterol (LDL-C, mg/dL)

    Time frame: Change from Baseline serum low-density lipoprotein cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Low-density lipoprotein cholesterol will be calculated using the Friedewald formula

  20. Change in serum triglycerides (TG, mg/dL)

    Time frame: Change from Baseline serum triglycerides at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Triglycerides will be determined by standardized spectrophotometry methods

  21. Change in serum alanine aminotransferase (ALT, U/L)

    Time frame: Change from Baseline serum alanine aminotransferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Alanine aminotransferase will be determined by standardized spectrophotometry methods

  22. Change in serum aspartate aminotransferase (AST, U/L)

    Time frame: Change from Baseline serum aspartate aminotransferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Aspartate aminotransferase will be determined by standardized spectrophotometry methods

  23. Change in serum gamma glutamyl transferase (GGT, U/L)

    Time frame: Change from Baseline serum gamma glutamyl transferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Gamma glutamyl transferase will be determined by standardized spectrophotometry methods

  24. Change in serum insulin levels (mU/L)

    Time frame: Change from Baseline serum insulin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Insulin levels will be measured by standardized chemiluminescence methods.

  25. Change in serum leptin levels (pg/mL)

    Time frame: Change from Baseline serum leptin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Leptin levels will be measured by standardized chemiluminescence methods

  26. Change in serum adiponectin levels (ng/mL)

    Time frame: Change from Baseline serum adiponectin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Adiponectin levels will be measured by standardized chemiluminescence methods

  27. Change in Adiponectin/Leptin ratio (numerical ratio)

    Time frame: Change from Baseline Adiponectin/Leptin ratio at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Adiponectin and leptin will be combined to report adiponectin/leptin ratio

  28. Change in serum Monocyte chemoattractant protein-1 (MCP-1) levels (pg/mL)

    Time frame: Change from Baseline serum MCP-1 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    MCP-1 levels will be measured by standardized chemiluminescence methods

  29. Change in plasma tumor necrosis factor alpha (TNF-alpha) levels (pg/mL)

    Time frame: Change from Baseline plasma TNF-alpha levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    TNF-alpha levels will be measured by standardized chemiluminescence methods

  30. Change in plasma Interleukin 6 (IL-6) levels (pg/mL)

    Time frame: Change from Baseline plasma IL-6 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    IL-6 levels will be measured by standardized chemiluminescence methods

  31. Change in plasma Interleukin 10 (IL-10) levels (pg/mL)

    Time frame: Change from Baseline plasma IL-10 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    IL-10 levels will be measured by standardized chemiluminescence methods

  32. Change in plasma Intercellular Adhesion Molecule 1 (ICAM-1) levels (ng/mL)

    Time frame: Change from Baseline plasma ICAM-1 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    ICAM-1 levels will be measured by standardized chemiluminescence methods

  33. Change in plasma Cluster of Differentiation 14 (CD14) levels (pg/mL)

    Time frame: Change from Baseline plasma CD14 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    CD14 levels will be measured by standardized chemiluminescence methods

  34. Change in plasma oxidized low density lipoproteins (LDLox) levels (mU/L)

    Time frame: Change from Baseline plasma LDLox levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    LDLox levels will be measured by standardized chemiluminescence methods

  35. Change in serum C-Reactive protein levels (mg/L)

    Time frame: Change from Baseline serum C-Reactive protein levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    C-Reactive protein levels will be determined by standardized spectrophotometry methods

  36. Change in Histidine levels in blood (umol/L)

    Time frame: Change from Baseline Histidine levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Serum histidine levels will be determined by Liquid Chromatography coupled to tandem Mass Spectrometry

  37. Change in Acylcarnitine levels in blood (umol/L)

    Time frame: Change from Baseline Acylcarnitine levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Serum Acylcarnitine levels will be determined by Liquid Chromatography coupled to tandem Mass Spectrometry

  38. Change in 17-beta-estradiol (E2) levels in blood (pg/mL)

    Time frame: Change from Baseline 17-beta-estradiol (E2) levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Serum 17-beta-estradiol (E2) levels will be determined by standardized chemiluminescence methods

  39. Change in Follicle-stimulating hormone (FSH) levels in blood (mU/mL)

    Time frame: Change from Baseline FSH levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Follicle-stimulating hormone (FSH) levels will be determined by standardized chemiluminescence methods

  40. Change in Homeostatic Model Assessment from Insulin Resistance Index (HOMA-IR)

    Time frame: Change from Baseline HOMA-IR at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    HOMA-IR will be calculated using serum glucose and insulin levels.

  41. Change in Fatty Liver Index (FLI)

    Time frame: Change from Baseline FLI at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    FLI will be calculated using BMI, waist circumference, serum triglycerides and gamma glutamyl transferase levels

  42. Change in Triglyceride glucose index (TyG)

    Time frame: Change from Baseline TyG at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    TyG will be calculated using serum glucose and triglycerides levels

  43. Change in Plasma atherogenic index

    Time frame: Change from Baseline Plasma atherogenic index at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Plasma atherogenic index will be calculated as the logarithm of the TG to HDL-c ratio

  44. Change in lipidomic profile

    Time frame: Change from Baseline Lipidomic profile at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Lipidomic analyses will be done by Liquid Chromatography coupled to tandem Mass Spectrometry

  45. Change in intestinal microbiota composition

    Time frame: Change from Baseline intestinal microbiota composition at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Metagenomic analysis in fecal samples. The bacteria DNA will be extracted and massive sequenced by the Ion Torrent platform.

  46. Change in the expression of lipid-metabolism genes in PBMC

    Time frame: Change from Baseline gene expression at 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Peripheral blood mononuclear cell (PBMC) will be isolated to obtain the RNA for gene expression analyses by Quantitative reverse transcription PCR (RT-qPCR)

  47. Change in Dietary habits

    Time frame: Change from Baseline Dietary habits at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Nutritional habits will be determined based on the results obtained from the 3-day dietary record

  48. Change in Physical activity

    Time frame: Change from Baseline Physical activity at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Physical activity will be evaluated through the International Physical Activity Questionnaire (IPAQ)-short for physical activity questionnaire. Scores will be reported in categories: LOW activity levels, MODERATE activity levels or HIGH activity levels with the latter indicating better outcomes.

  49. Concomitant medication

    Time frame: At day -7 (pre-selection visit), day 1 (visit V1), day 43 (visit 2) and day 85 (visit 3)

    Concomitant medication consumed during the study will be recorded in the case report form.

  50. Consumption of dietary supplements

    Time frame: At day -7 (pre-selection visit), day 1 (visit V1), day 43 (visit 2) and day 85 (visit 3)

    Dietary supplements consumed during the study will be recorded in the case report form.

  51. Change in the Supraclavicular skin temperature

    Time frame: Change from Baseline Supraclavicular skin temperature at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Supraclavicular skin temperature will be measured with the FLIR T530 thermal imaging camera

  52. Change in postmenopausal symptoms

    Time frame: Change from Baseline postmenopausal symptoms at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

    Postmenopausal symptoms will be evaluated through the Menopause Rating Scale (MRS) questionnaire. The MRS comprises 11 items representing various symptoms or complaints. Each symptom can be rated from 0 (indicating no complaints) to 4 points (indicating severe symptoms), depending on the perceived severity reported by the women completing the scale. The total MRS score ranges from 0 (asymptomatic) to 44 (maximum complaint severity).

  53. Adverse events

    Time frame: At 6 weeks (V2) and at 12 weeks (V3) for each of the two treatments (multi-ingredient and placebo)

    Possible adverse events derived from taking study's products will be recorded in the case report form

Sponsors and collaborators

Lead sponsor

Fundació Eurecat

Other

Collaborators

  • Centre de Diagnosi per la Imatge
  • Instituto de Investigación Biomédica de Girona (IDIBGI)
  • Laboratorio de Referencia de Cataluña

Registry information

Official study title

Effect of a Multi-ingredient of L-Histidine, L-Serine, L-Carnosine and N-Acetylcysteine on Visceral Adiposity and Non-alcoholic Fatty Liver Disease in Postmenopausal Women With Abdominal Obesity

Acronym: FATHIS+

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Apr 22, 2024
Registry last updated
Apr 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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