Effect of Methylfolate, Pyridoxal-5′-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Population and Design
- 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) [4].
- Personal history of cardiovascular disease or high risk (≥20%);
- Triglycerides (TG) ≥ 400 mg/dL;
- Obesity (Body Mass Index > 30 kg/m2);
- 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.
2.2. Study Endpoints and Assessments
2.3. Sample Size Calculation and Statistical Power
2.4. Statistical Analyses
3. Results
3.1. Primary Endpoint
3.2. Other Secondary End Points
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Methylfolate, P5P, Methylcobalamin (n = 26) | Placebo (n = 25) | p-Value | Homozygous Minor Allele Carriers (n = 18) | Mixed Allele Carriers (n = 33) | p-Value | |
---|---|---|---|---|---|---|
Age, y | 59.2 ± 6.2 | 57.5 ± 9.1 | p = 0.45 | 57.3 ± 7.8 | 59.1 ± 8.9 | p = 0.07 |
Women, % | 57.7 | 52.0 | p = 0.61 | 60 | 52 | p = 0.21 |
Body mass index, kg/m2 | 27.5 ± 3.1 | 28.9 ± 3.3 | p = 0.33 | 29.2 ± 3.2 | 27.5 ± 3.6 | p = 0.09 |
10-y ASCVD risk, % | 9.9 | 8.5 | p = 0.75 | 10 | 8.5 | p = 0.11 |
Homocysteine, μmol/L | 18.5 ± 4.1 | 19.1 ± 3.8 | p = 0.81 | 25.1 ± 4.1 | 17.3 ± 3.9 | p < 0.01 |
Total cholesterol, mg/dL | 180 ± 21 | 185 ± 31 | p = 0.68 | 190 ± 29 | 180 ± 25 | p = 0.08 |
LDL-C, mg/dL | 125.4 ± 27.2 | 131.7 ± 29.1 | p = 0.57 | 150.1 ± 29.3 | 127.7 ± 26.8 | p < 0.01 |
HDL-C, mg/dL | 52.4 ± 6.5 | 48.9 ± 4.1 | p = 0.11 | 47.6 ± 4.8 | 52.2 ± 5.8 | p = 0.05 |
Triglycerides, mg/dL | 159 ± 32 | 148 ± 27 | p = 0.42 | 165 ± 29 | 147 ± 25 | p = 0.18 |
hsCRP, mg/L | 1.8 ± 0.7 | 2.5 ± 1.1 | p = 0.09 | 2.5 ± 0.9 | 2.0 ± 1.2 | p = 0.23 |
Methylfolate, P5P, Methylcobalamin (n = 26) % Change from Baseline (95% CI) | Placebo (n = 25) % Change from Baseline (95% CI) | % Difference (95% CI) | p-Value | |
---|---|---|---|---|
Homocysteine | −30.0% (−39.7%, −20.3%) | 1.8% (−4.8%, 6.8%) | −31.8% (−46.5%, −15.5%) | p < 0.01 |
LDL-C | −7.5% (−10.3%, −4.7%) | 2.6% (−1.6%, 5.6%) | −10.1% (−15.9%, −3.1%) | p < 0.01 |
Total cholesterol | −2.5% (−4.8%, −0.3%) | 2.1% (−0.6%, 4.8%) | −4.6% (−9.6%, 0.3%) | p = 0.08 |
HDL-C | 1.6% (−1.4%, 4.6%) | −0.5% (−3.0%, 2.0%) | 2.1% (−3.4%, 7.6%) | p = 0.16 |
Triglycerides | −3.7% (−7.7%, 0.3%) | 2.8% (−0.3%, 5.9%) | −6.5% (−13.6%, 0.6%) | p = 0.11 |
hsCRP | −5.3% (−13.0%, 2.5%) | −3.2% (−8.3%, 1.9%) | −2.1% (−14.9%, 10.8%) | p = 0.23 |
Homozygous Minor Allele Carriers (n = 10) % Change from Baseline (95% CI) | Mixed Allele Carriers (n = 16) % Change from Baseline (95% CI) | % Difference (95% CI) | p-Value | |
---|---|---|---|---|
Homocysteine | −48.3% (−62.3%, −34.3%) | −18.6% (−25.6%, −11.6%) | −29.7% (−50.7%, −8.7%) | p < 0.01 |
LDL-C | −11.8% (−15.8%, −7.8%) | −4.8% (−6.8%, −2.8%) | −7.0% (−13.0%, −1.0%) | p < 0.01 |
Total cholesterol | −3.2% (−5.6%, −0.8%) | −2.1% (−4.3%, 0.1%) | −1.1% (−5.7%, 3.5%) | p = 0.07 |
HDL-C | 2.8% (−0.5%, 6.1%) | 0.9% (−1.9%, 3.7%) | 1.9% (−4.2%, 8.0%) | p = 0.12 |
Triglycerides | −5.1% (−10.9%, 0.7%) | −2.8% (−5.7%, 0.1%) | −2.3% (−11.0%, 6.4%) | p = 0.09 |
hsCRP | −3.9% (−11.6%, 3.8%) | −6.1% (−13.9%, 1.7%) | 2.2% (−17.7%, 13.3%) | p = 0.22 |
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Pokushalov, E.; Ponomarenko, A.; Bayramova, S.; Garcia, C.; Pak, I.; Shrainer, E.; Ermolaeva, M.; Kudlay, D.; Johnson, M.; Miller, R. Effect of Methylfolate, Pyridoxal-5′-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial. Nutrients 2024, 16, 1550. https://doi.org/10.3390/nu16111550
Pokushalov E, Ponomarenko A, Bayramova S, Garcia C, Pak I, Shrainer E, Ermolaeva M, Kudlay D, Johnson M, Miller R. Effect of Methylfolate, Pyridoxal-5′-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial. Nutrients. 2024; 16(11):1550. https://doi.org/10.3390/nu16111550
Chicago/Turabian StylePokushalov, Evgeny, Andrey Ponomarenko, Sevda Bayramova, Claire Garcia, Inessa Pak, Evgenya Shrainer, Marina Ermolaeva, Dmitry Kudlay, Michael Johnson, and Richard Miller. 2024. "Effect of Methylfolate, Pyridoxal-5′-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial" Nutrients 16, no. 11: 1550. https://doi.org/10.3390/nu16111550