Effect of Vitamin K2 Over Osteocalcin, Leptin, Cytokines, and Cardiovascular Risk in Young Adults With Overweight and Obesity

Effect of Vitamin K2 Supplementation and Its Association With Osteocalcin Serum Levels, Leptin, Th1/Th2 Cytokine Profile, and Cardiovascular Risk in Young Mexican Adults With Overweight and Obesity

The goal of this clinical trial is to compare de effect of vitamin K2 in young adults with overweight or obesity. The main questions to answer are:

What is the effect of Vitamin K2 supplementation on methylation, serum concentration of ucOC, cOC, Gas6, leptin, inflammatory markers, cardiometabolic risk factors, and cardiovascular risk in overweight or obese young adults? Participants will be assigned to one of two intervention groups where they will consume Vitamin K2 100 µg per day or cornstarch 500 mg per day for 90 days.

If there is a comparison group: Investigators will compare the supplementation group (Vitamin K2) with the placebo group (cornstarch) to see if vitamin K2 supplementation modifies methylation, increases serum vitamin K, osteocalcin, growth arrest-specific 6 protein serum concentration, decreases serum leptin concentration, inflammatory markers and reduces cardiometabolic risk factors and cardiovascular risk.

Study Overview

• Status: Not yet recruiting
• Conditions: Overweight and Obesity; Cardiometabolic Risk Factors
• Intervention / Treatment: Dietary supplement: Vitamin K2; Other: Cornstarch

Detailed Description

Study Overview To meet the objectives of the project, two groups will be compared, one that will be supplemented with vitamin K and another of patients who will receive corn starch as a placebo. Patients are going to have a follow up during 3 months with periodic evaluations every 30 days.

This is a double-blind study, it is achieved by maintaining similarities in appearance, taste and smell between the treatments that will be delivered in the same vials, with same number of pills and identical in shape, color and consistency for each study group.

Patient recruitment will take place by disseminating information through physical and social media, once potential participants have been identified, they will be contacted and informed about the project, and if they decide to participate in the study, they will be asked to sign the informed consent.

Simple randomization will be performed using R software to assign participants to one of the study groups. A clinical history, anthropometric measurements and blood sampling shall be applied.

Nutritional recommendations based on the position of the Academy of Nutrition and Dietetics for the treatment of overweight and obesity and the healthy eating plate of Harvard University will be given. An appointment is to be scheduled every 30 days in order to provide the supplementation and follow-up. At the end, the pertinent statistical analyzes will be carried out.

Notification of adverse effects will be made in each of the sessions, in addition to this the participants will have the contact of the researchers to notify any anomaly.

Sample's size calculation

The sample size was calculated using the statistical formula for the comparison of two means. This estimate was made using the following formula:

n=2(Zα+Z[1-β]2xSD2/d2

Where:

n= sample size required in each group SD= standard deviation of the effect Zα: to the value of Z for a confidence level of 95% Z[1-β}: to the value of Z for a statistical power of 80% D= effect size A total of 19.72 patients per group were obtained. Considering a 20% loss, 24 patients are needed per study group.

Ethical considerations The study was approved by the Biosafety committee, research ethics committee and research committee of the University Center for Health Sciences, University of Guadalajara: CI-00421. The committees of the University have the authority to monitor and audit the study at any of its stages once it has been approved.

Objetives General objective Evaluate the effect of vitamin K2 supplementation on methylation, the serum concentration of total vitamin K, osteocalcin, growth arrest-specific 6 protein, leptin, inflammatory markers, cardiometabolic risk factors and cardiovascular risk in young Mexican adults with overweight or obesity.

Specific objectives

1. Compare the baseline variables between groups.
2. Compare the variable changes across the time within groups
3. Compare the variable changes across the time between groups

Statistical analysis The Shapiro-Wilk normality test is performed to determine whether the analysis will require parametric or non-parametric tests. Qualitative variables will be expressed as frequencies and percentages, while quantitative variables will be expressed as mean and standard deviation in parametric data or medians and ranges in non-parametric data.

Specific objective 1 Statistical technique T-student for independent samples if it has a normal distribution or by U-Mann Whitney for independent samples if it does not have a normal distribution

Specific objective 2 Variables with two measures Statistical technique T-student for paired samples if it has a normal distribution or the Wilcoxon signed-rank test if it does not have a normal distribution

Variables with more than two measures Statistical technique Repeated measures ANOVA if it has a normal distribution or the Friedman Test if it does not have a normal distribution

Specific objective 3 Statistical technique The effect size of the groups is compared with T-student for independent samples if it has a normal distribution or by U-Mann Whitney for independent samples if it does not have a normal distribution

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrés López Quintero, PhD; Phone Number: 34294 33 1058 5200; Email: andres.lopezq@academicos.udg.mx
• Study Contact Backup: Name: Edgar A Rivera León, PhD; Phone Number: 56928 (378) 782 8033; Email: edgar.rleon@academicos.udg.mx

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • University of Guadalajara
      • Contact: Andrés López Quintero, PhD; Phone Number: 34294 33 1058 5200; Email: andres.lopezq@academicos.udg.mx
      • Contact: Edgar A Rivera León, PhD; Phone Number: 56928 (378) 782 8033; Email: edgar.rleon@academicos.udg.mx
      • Principal Investigator: Andrés López Quintero, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body Mass Index greater than 25 kg/m2 and less than 40 kg/m2
• That they agree to participate in the study voluntarily and informed and sign the informed consent

Exclusion Criteria:

• People with self-reported diagnosis of chronic kidney, gastrointestinal or systemic disease
• Use of bile acid sequestrants drugs, insulin, glucocorticoids, contraceptives, bisphosphonates, thiazides, levetiracetam, thiazolidinediones, anticoagulants or estrogenic drugs and vitamin D, vitamin K, vitamin A, vitamin E, omegas or calcium supplements
• Patients who are on a hypocaloric or low-fat diet
• Self-reported pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supplementation arm; Vitamin K2	Dietary supplement: Vitamin K2; 100 µg per day for 90 days; Other Names: Nutricost Menaquinone-4 100 µg
Placebo Comparator: Placebo arm; Cornstarch	Other: Cornstarch; 500 mg per day for 90 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Osteocalcin serum concentration	ng/dL	Baseline and after 90 days of intervention
Vitamin K serum concentration	ng/dL	Baseline and after 90 days of intervention
Leptin serum concentration	ng/dL	Baseline and after 90 days of intervention
Tumour Necrosis Factor alpha serum concentration	pg/mL	Baseline and after 90 days of intervention
Interleukin-1 Beta serum concentration	pg/mL	Baseline and after 90 days of intervention
Interleukin-6 serum concentration	pg/mL	Baseline and after 90 days of intervention
Interleukin-4 serum concentration	pg/mL	Baseline and after 90 days of intervention
Interleukin-10 serum concentration	pg/mL	Baseline and after 90 days of intervention
Cardiovascular risk	percentage	Baseline, after 30, 60 and 90 days of intervention
LEP gene methylation	Methylated or unmethylated	Baseline and after 90 days of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth arrest-specific 6 protein serum concentration	ng/ml	Baseline and after 90 days of intervention
Global methylation	percentage	Baseline and after 90 days of intervention
Atherogenic indices	Value	Baseline and after 90 days of intervention
Triglycerides serum concentration	mg/dL	Baseline and after 90 days of intervention
Total cholesterol serum concentration	mg/dL	Baseline and after 90 days of intervention
HDL cholesterol serum concentration	mg/dL	Baseline and after 90 days of intervention
LDL cholesterol serum concentration	mg/dL	Baseline and after 90 days of intervention
VLDL cholesterol serum concentration	mg/dL	Baseline and after 90 days of intervention
Glucose serum concentration	mg/dL	Baseline and after 90 days of intervention
Blood pressure	mmHg	Baseline, after 30, 60 and 90 days of intervention
Insulin serum concentration	µIU/ml	Baseline and after 90 days of intervention
Weight	kg	Baseline, after 30, 60 and 90 days of intervention
Body mass index	kg/m2	Baseline, after 30, 60 and 90 days of intervention
Waist circumference	cm	Baseline, after 30, 60 and 90 days of intervention
Hip circumference	cm	Baseline, after 30, 60 and 90 days of intervention
Fat mass	kg	Baseline, after 30, 60 and 90 days of intervention
% fat	percentage	Baseline, after 30, 60 and 90 days of intervention
Lean mass	kg	Baseline, after 30, 60 and 90 days of intervention
Estimated energy consumption	kcal/day	Baseline, after 30, 60 and 90 days of intervention
Estimated protein consumption	grams/day	Baseline, after 30, 60 and 90 days of intervention
Estimated carbohydrates consumption	grams/day	Baseline, after 30, 60 and 90 days of intervention
Estimated fat consumption	grams/day	Baseline, after 30, 60 and 90 days of intervention
Estimated vitamin K consumption	μg/day	Baseline, after 30, 60 and 90 days of intervention

Collaborators and Investigators

• Sponsor: University of Guadalajara
• Investigators: Principal Investigator: Andrés López Quintero, PhD

Publications and helpful links

General Publications

• Aguayo-Ruiz JI, Garcia-Cobian TA, Pascoe-Gonzalez S, Sanchez-Enriquez S, Llamas-Covarrubias IM, Garcia-Iglesias T, Lopez-Quintero A, Llamas-Covarrubias MA, Trujillo-Quiroz J, Rivera-Leon EA. Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial. Diabetol Metab Syndr. 2020 Aug 18;12:73. doi: 10.1186/s13098-020-00580-w. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): November 30, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: August 8, 2023
• First Submitted That Met QC Criteria: August 8, 2023
• First Posted (Actual): August 16, 2023

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Cardiometabolic Risk Factors; Vitamin K; Overweight and Obesity
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Obesity; Overweight; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K; Vitamin K 2
• Other Study ID Numbers: CI-00421

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No