Evaluating the Impact of B Vitamin Supplementation (Soloways™) on Homocysteine and LDL-C Levels in Patients With MTHFR, MTR, and MTRR Polymorphisms.

Study Overview
=================
Brief Summary
-----------------
This randomized, double-blind, placebo-controlled trial will evaluate the impact of methylfolate, pyridoxal-5'-phosphate (P5P), and methylcobalamin supplementation on homocysteine and LDL-C levels in individuals with low to medium cardiac risk and MTHFR, MTR, and MTRR gene polymorphisms. The study aims to explore the efficacy of these vitamins in reducing homocysteine levels, a critical risk factor for cardiovascular disease (CVD), while also monitoring LDL-C levels. The findings will offer valuable insights into personalized CVD prevention and management, emphasizing the significance of genetic factors in nutritional therapy.

Detailed Description
-----------------
Design: Participants with specific genetic polymorphisms and homocysteine levels above 15 µmol/L, without a history of severe CVD or other exclusion criteria, will be enrolled and randomized into two groups: one receiving methylfolate, P5P, and methylcobalamin, and the other a placebo. The study, adhering to ethical standards and informed consent, will involve 54 patients divided equally between the treatment and placebo groups. The primary endpoint will be the percent change in homocysteine levels over six months, with secondary endpoints including changes in LDL-C and other lipid profile components. Intervention: Participants will receive either the active treatment (L-methylfolate, P5P, and Methylcobalamin) or a placebo, with both groups taking two capsules daily for 180 days. Fasting measurements of lipid profiles and homocysteine levels will be conducted at the start, midpoint, and end of the study.

Official Title
-----------------
Evaluating the Impact of B Vitamin Supplementation (Soloways™) on Homocysteine and LDL-C Levels in Patients With MTHFR, MTR, and MTRR Polymorphisms: A Randomized, Double-blind, Placebo-controlled Trial

Conditions
-----------------
Hyperhomocysteinemia, Hyperlipoproteinemias

Intervention / Treatment
-----------------
* Dietary Supplement: Vitamin B
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 40 and 75. Homocysteine levels greater than 15 µmol/L and LDL-C level between 70 and 190 mg/dL, confirmed in at least two sequential checks conducted within the last six months prior to signing the consent form. Presence of at least one minor allele in any of the following genetic polymorphisms: rs1801133 (MTHFR C677T), rs1801131 (MTHFR A1298C), rs1805087 (MTR A2756G), and rs1801394 (MTRR A66G). Exclusion Criteria: Personal history of cardiovascular disease or high risk (≥ 20%). Triglycerides (TG) ≥ 400 mg/dL. Obesity (Body Mass Index > 32 kg/m^2). Assumption of lipid-lowering drugs or supplements affecting lipid metabolism within the last three months. Use of medications or supplements known to affect homocysteine levels, such as B-vitamins and certain antihypertensives, within the last three months. Diabetes mellitus. Known severe or uncontrolled thyroid, liver, renal, or muscle diseases.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin B group<br>Patients with polymorphisms in the MTHFR, MTR, and MTRR will take methylfolate, P5P, and methylcobalamin genes 2 capsules/day. | Dietary Supplement: Vitamin B<br>* MTHFR, MTR, and MTRR polymorphysm based L-methylfolate (1 mg), P5P (pyridoxal-5-phosphate, 50 mg), and Methylcobalamin (500 mcg) prescription<br>|
| Placebo Comparator: Placebo group<br>Patients with polymorphisms in the MTHFR, MTR, and MTRR will take placebo capsules will be identical in appearance, matched for color coating, shape, and size - 2 capsules/day.. | Dietary Supplement: Placebo<br>* MTHFR, MTR, and MTRR polymorphysm based placebo prescription<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Homocysteine levels | The primary endpoint is the percent change in homocysteine levels from baseline to 6 months of observation, comparing a combined treatment regimen of methylfolate, P5P, and methylcobalamin in MTHFR, MTR, and MTRR polymorphysm. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LDL-C Levels | Percent change in Low-Density Lipoprotein Cholesterol (LDL-C) levels. | 180 days | 
| Change in HDL-C Levels | Percent change in High-Density Lipoprotein Cholesterol (HDL-C) levels. | 180 days | 
| Change in Total Cholesterol | Percent change in total cholesterol levels in the study participants. | 180 days | 
| Change in Serum Triglycerides | Percent change in serum triglycerides. | 180 days | 
| Change in hsCRP Levels | Percent change in high-sensitivity C-Reactive Protein (hsCRP) levels. | 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Methylfolate, Homocysteine, Genetic Polymorphisms (MTHFR, MTR, MTRR), Cardiovascular Risk, Methylcobalamin, LDL-C, Cholesterol, Low-Density Lipoprotein