Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants–Eligibility Criteria
2.2. Randomization and Allocation
2.3. Protocol Registration
2.4. Biochemical Tests
2.5. Neuropathy Assessment and Tests
2.6. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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All | Active Group | Placebo Group | p | |
---|---|---|---|---|
Gender (m/w) | 36/37 | 16/20 | 20/17 | 0.204 |
Age (years) | 63.0 ± 9.9 | 64.5 ± 10.8 | 61.5 ± 8.9 | 0.243 |
Height (cm) | 166 ± 9 | 165 ± 9 | 167 ± 9 | 0.393 |
Body weight (kg) | 85.4 ± 9.2 | 84.0 ± 10.2 | 86.7 ± 8.0 | 0.251 |
BMI (kg/m2) | 31.0 ± 4.2 | 30.9 ± 4.3 | 31.2 ± 4.1 | 0.778 |
Diabetes duration (years) | 17.5 ± 7.3 | 17.9 ± 8.3 | 17.1 ± 6.2 | 0.632 |
Only OADs, incl. metformin (n,%) | 45 (61.6%) | 21 (58.3%) | 24 (64.9%) | 0.667 |
OADs and basal insulin (n,%) | 28 (38.4%) | 15 (41.7%) | 13 (35.1%) | 0.568 |
Smoking (n,%) | 15 (22%) | 7 (20%) | 8 (24.2%) | 0.110 |
Cardiovascular Disease (n,%) | 28 (41.2%) | 15 (42.8%) | 13 (39.4%) | 0.587 |
Dyslipidemia (n,%) | 52 (76.5%) | 28 (80%) | 24 (72.7%) | 0.853 |
Hypertension (n,%) | 54 (79.4%) | 26 (74.3%) | 28 (84.8%) | 0.781 |
HbA1c (%) | 7.0 ± 0.9 | 7.0 ± 0.9 | 7.1 ± 0.8 | 0.817 |
Vitamin B12 (pg/mL) | 230.3 ± 90.9 | 222.1 ± 87.5 | 238.3 ± 94.9 | 0.493 |
All | Active Group (n = 36) | Placebo Group (n = 37) | p of Change | |||||
---|---|---|---|---|---|---|---|---|
Baseline | Follow Up | p | Baseline | Follow Up | p | |||
Total Cholesterol (mg/dL) | 162.3 ± 37 | 158.06 ± 32.8 | 159.2 ± 30.8 | 0.229 | 166.7 ± 41.1 | 165.5 ± 40.7 | 0.282 | 0.339 |
HDL Cholesterol (mg/dL) | 47.7 ± 11.7 | 46.9 ± 12.8 | 46.7 ± 12.7 | 0.213 | 48.6 ± 10.5 | 48.8 ± 10.4 | 0.160 | 0.472 |
LDL cholesterol (mg/dL) | 86.8 ± 28.9 | 84.3 + 30.6 | 85.7 ± 28.9 | 0.243 | 89.3 ± 30.8 | 87.9 ± 29.7 | 0.756 | 0.345 |
Triglycerides (mg/dL) | 139.3 ± 43 | 134.4 ± 39.9 | 133.5 ± 38.5 | 0.593 | 144.5 ± 46.1 | 144.3 ± 44.6 | 0.891 | 0.339 |
TSH | 2.3 ± 0.8 | 2.4 ± 0.7 | 2.4 ± 0.7 | 0.247 | 2.3 ± 0.8 | 2.3 ± 0.8 | 0.160 | 0.09 |
AST | 18.9 ± 8 | 20.1 ± 9.9 | 19.9 ± 9.8 | 0.481 | 17.5 ± 5.2 | 17.4 ± 5.2 | 0.484 | 0.192 |
ALT | 21.9 ± 10.1 | 21.9 ± 11.5 | 21.8 ± 11.3 | 0.912 | 22 ± 8.6 | 21.7 ± 7.8 | 0.299 | 0.477 |
Urea (mg/dL) | 34.2 ± 11.5 | 33.4 ± 9.2 | 33.4 ± 9.2 | 0.737 | 35.1 ± 13.5 | 34.9 ± 13.6 | 0.563 | 0.279 |
Creatinine (mg/dL) | 0.9 ± 0.2 | 0.9 ± 0.2 | 0.9 ± 0.2 | 0.612 | 0.9 ± 0.2 | 0.8 ± 0.2 | 0.326 | 0.365 |
Ht (%) | 40.5 ± 2.9 | 40.7 ± 2.9 | 40.6 ± 2.8 | 0.454 | 40.3 ± 2.9 | 40.4 ± 2.8 | 0.694 | 0.323 |
MCV | 85.5 ± 3.9 | 84.9 ± 4 | 86.2 ± 3.6 | 0.342 | 86.2 ± 3.6 | 86 ± 3.5 | 0.492 | 0.177 |
WBC | 7.9 ± 1.4 | 7.9 ± 1.5 | 7.9 ± 1.4 | 0.424 | 7.9 ± 1.4 | 7.9 ± 1.3 | 0.560 | 0.894 |
PLT | 239.1 ± 5.7 | 246.1 ± 41 | 249 ± 40.7 | 0.159 | 231.8 ± 58.9 | 233.7 ± 58.8 | 0.188 | 0.246 |
HbA1c (%) | 7.0 ± 0.9 | 7.0 ± 0.9 | 6.83 ± 0.3 | 0.289 | 7.1 ± 0.8 | 6.9 ± 0.3 | 0.341 | 0.749 |
B12 (pg/mL) | 230.3 ± 90.9 | 222.1 ± 87.5 | 576.3 ± 201.5 | <0.001 | 238.3 ± 94.9 | 264.3 ± 106.1 | 0.081 | <0.001 |
All | Active Group (n = 36) | Placebo Group (n = 37) | p | |
---|---|---|---|---|
MNSIQ | 6.2 ± 1.7 | 6.13 ± 1.9 | 6.3 ± 1.5 | 0.779 |
MNSIE | 3.3 ± 2.2 | 3.6 ± 1.9 | 2.9 ± 2.4 | 0.241 |
Pain score | 20.4 ± 7.7 | 20.9 ± 7.4 | 21.6 ± 7.9 | 0.224 |
SNAP (μV) | 5.9 ± 4.1 | 6.5 ± 3.8 | 5.4 ± 4.4 | 0.281 |
SNCV (m/s) | 29.4 ± 22.6 | 28.8 ± 22.7 | 30 ± 22.9 | 0.831 |
VPT (V) | 30.6 ± 14.5 | 32.1 ± 14.5 | 29.2 ± 14.5 | 0.437 |
MCR | 20 ± 30.9 | 18.4 ± 34.6 | 21.8 ± 27.8 | 0.789 |
PI | 4.3 ± 6.6 | 5.9 ± 8.9 | 2.5 ± 0.9 | 0.200 |
PO (mmHg) | 8.9 ± 11.8 | 10.7 ± 12.8 | 7.1 ± 10.8 | 0.456 |
ESCF (μS) | 76.9 ± 11.5 | 72.2 ± 10.7 | 75.6 ± 11.7 | 0.775 |
ESCH (μS) | 68 ± 10.5 | 68.4 ± 11.1 | 67.6 ± 10.2 | 0.764 |
Active Group (n = 36) | Placebo Group (n = 37) | p for Difference between Groups | |||||
---|---|---|---|---|---|---|---|
Baseline | Follow Up | p | Baseline | Follow Up | p | ||
HbA1c (%) | 7 ± 0.9 | 6.83 ± 0.3 | 0.289 | 7.1 ± 0.8 | 6.9 ± 0.3 | 0.341 | 0.749 |
B12 (pg/mL) | 222.1 ± 87.5 | 576.3 ± 201.5 | <0.001 | 238.3 ± 94.9 | 264.3 ± 106.1 | 0.081 | <0.001 |
MNSIQ | 6.13 ± 1.9 | 5.9 ± 1.8 | 0.017 | 6.3 ± 1.5 | 6.23 ± 1.5 | 0.712 | 0.117 |
MNSIE | 3.6 ± 1.9 | 3.7 ± 1.8 | 0.161 | 2.9 ± 2.4 | 3.4 ± 2.4 | <0.001 | 0.009 |
Pain score | 20.9 ± 7.1 | 13.9 ± 6.1 | <0.001 | 21.6 ± 7.9 | 21.7 ± 8.4 | 0.870 | <0.001 |
Quality of life | 38.3 ± 11.6 | 35.6 ± 10.3 | <0.001 | 38.3 ± 10.4 | 38.8 ± 9.7 | 0.208 | 0.779 |
SNAP (μV) | 6.5 ± 3.8 | 7.2 ± 3.6 | 0.055 | 5.4 ± 4.4 | 5.4 ± 4.3 | 0.897 | 0.101 |
SNCV (m/s) | 28.8 ± 22.7 | 30.4 ± 23.04 | 0.001 | 30 ± 22.9 | 29.4 ± 23.5 | 0.564 | 0.052 |
VPT (V) | 32.1 ± 14.5 | 26.7 ± 12.9 | 0.001 | 29.2 ± 14.5 | 28.5 ± 13.7 | 0.618 | 0.025 |
MCR | 18.4 ± 34.6 | 14.6 ± 15.3 | 0.686 | 21.8 ± 27.8 | 17.5 ± 28.3 | 0.695 | 0.951 |
PI | 5.9 ± 8.9 | 5.7 ± 9.7 | 0.833 | 2.5 ± 0.9 | 1.9 ± 1.3 | 0.195 | 0.946 |
PO (mmHg) | 10.7 ± 12.8 | 5.5 ± 9.1 | 0.211 | 7.1 ± 10.8 | 6.3 ± 9.8 | 0.765 | 0.377 |
Valsalva | 1.5 ± 0.2 | 1.6 ± 0.2 | 0.883 | 1.5 ± 0.3 | 1.5 ± 0.2 | 0.963 | 0.971 |
ESCF (μS) | 72.2 ± 10.7 | 74.8 ± 10.8 | <0.001 | 75.6 ± 11.7 | 75.8 ± 11.6 | 0.731 | 0.239 |
ESCH (μS) | 68.4 ± 11.1 | 69.2 ± 10.5 | 0.567 | 67.6 ± 10.2 | 68.5 ± 8.9 | 0.467 | 0.937 |
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Didangelos, T.; Karlafti, E.; Kotzakioulafi, E.; Giannoulaki, P.; Kontoninas, Z.; Kontana, A.; Evripidou, P.; Savopoulos, C.; Birkenfeld, A.L.; Kantartzis, K. Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy. Nutrients 2024, 16, 3045. https://doi.org/10.3390/nu16183045
Didangelos T, Karlafti E, Kotzakioulafi E, Giannoulaki P, Kontoninas Z, Kontana A, Evripidou P, Savopoulos C, Birkenfeld AL, Kantartzis K. Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy. Nutrients. 2024; 16(18):3045. https://doi.org/10.3390/nu16183045
Chicago/Turabian StyleDidangelos, Triantafyllos, Eleni Karlafti, Evangelia Kotzakioulafi, Parthena Giannoulaki, Zisis Kontoninas, Anastasia Kontana, Polykarpos Evripidou, Christos Savopoulos, Andreas L. Birkenfeld, and Konstantinos Kantartzis. 2024. "Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy" Nutrients 16, no. 18: 3045. https://doi.org/10.3390/nu16183045