Evaluation of a High Concentrate Omega-3 for Correcting the Omega-3 Fatty Acid Nutritional Deficiency in Non-Alcoholic Fatty Liver Disease (CONDIN)
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Inclusion and Exclusion Criteria
2.3. Measurement of RBC EPA and DHA
2.3.1. Quantitative Measurement of RBC EPA and DHA
2.3.2. Qualitative Measurement of RBC EPA and DHA
2.4. Assessment of Change in Liver Fat
2.5. Calculation of Fatty Liver Index (FLI) Score
2.6. Sample Size Calculations
2.7. Statistical Analysis
3. Results
3.1. Effect of Intervention on Omega-3 Index
3.2. Effect of Intervention on RBC EPA + DHA, EPA and DHA Values
3.3. Effect of Intervention on RBC Omega-6: Omega-3 Ratio
3.4. Effect of Intervention on Liver Fat
3.5. Relationship between RBC EPA + DHA Enrichment and Liver Fat Content
3.6. Relationship between Baseline Fatty Liver Index (FLI) and Change in Liver Fat Content
3.7. Relationship between RBC EPA + DHA Enrichment and Liver Enzymes AST and ALT
3.8. Effect of Intervention on Plasma Triglycerides
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Variables | Placebo 1 | MF4637 2 | p-Value * |
---|---|---|---|
Age, years | 55.1 (10.9) | 55.3 (13.3) | 0.93 |
Sex, M/F | 44/42 | 36/45 | 0.39 |
Weight, kg | 90.1 (18.8) | 88.4 (18.4) | 0.55 |
Waist circumference, cm | 105.9 (13.1) | 106.3 (13.2) | 0.87 |
Hip circumference, cm | 110.5 (12.1) | 110.9 (11.8) | 0.85 |
Waist to hip ratio | 0.96 (0.09) | 0.96 (0.08) | 0.95 |
BMI, kg/m2 | 32.4 (5.0) | 32.1 (4.8) | 0.59 |
Systolic blood pressure, mm Hg | 127.0 (10.7) | 128.0 (11.9) | 0.64 |
Diastolic blood pressure, mm Hg | 80.3 (7.2) | 79.8 (7.6) | 0.33 |
Heart rate, beats/min | 74.7 (8.7) | 73.2 (9.1) | 0.25 |
Statin use, % | 34.9 | 30.9 | 0.58 |
Diabetes, % | 39.5 | 35.0 | 0.97 |
Fasting glucose, mg/dL | 120.1 (48.5) 2 | 119.4 (38.1) 3 | 0.97 |
Fasting insulin, µIU/mL | 30.2 (41.3) | 20.8 (18.2) 4 | 0.04 |
HbA1c, % | 6.5 (1.5) 5 | 6.3 (1.4) 6 | 0.20 |
Triglycerides, mg/dL | 199.1 (123.0) 7 | 192.0 (125.1) 4 | 0.70 |
BUN, mg/dL | 14.7 (4.9) 7 | 15.4 (5.0) 4 | 0.24 |
Creatinine, mg/dL | 0.8 (0.2) 7 | 0.3 (0.2) 4 | 0.83 |
TSH µIU/mL | 1.9 (1.0) 7 | 1.7 (0.9) 8 | 0.17 |
Hs-CRP, mg/L | 6.4 (9.2) 7 | 8.1 (17.5) | 0.61 |
Albumin, g/dL | 4.29 (0.3) 7 | 4.29 (0.3) 4 | 0.91 |
ALT, IU/L | 35.6 (24.0) | 37.5 (39.0) | 0.40 |
AST, IU/L | 25.8 (12.2) | 27.1 (20.3) | 0.79 |
ALP, IU/L | 81.5 (31.0) | 85.5 (45.3) | 0.62 |
GGT, IU/L | 47.1 (49.0) | 62.2 (151.4) | 0.78 |
Bilirubin, mg/dL | 0.5 (0.2) | 0.5 (0.3) | 0.91 |
Variables | Placebo 1 | MF4637 2 | Two-Sample Test for Change from Baseline p-Value # | ||||
---|---|---|---|---|---|---|---|
Baseline | End of Study | p-Value * | Baseline | End of Study | p-Value * | ||
Age, years | 55.1 (10.9) | 55.3 (13.3) | |||||
Sex, M/F | 44/42 | 36/45 | |||||
Weight, kg | 90.1 (18.8) | 89.5 (18.5) | 0.84 | 88.4 (18.4) | 89.0 (18.8) | 0.082 | 0.23 |
Waist circumference, cm | 105.9 (13.1) | 104.7 (13.9) | 0.005 | 106.3 (13.2) | 105.5 (12.2) | 0.72 | 0.18 |
Hip circumference, cm | 110.5 (12.1) | 110.0 (11.7) | 0.31 | 110.9 (11.8) | 110.4 (11.9) | 0.81 | 0.42 |
Waist to hip ratio | 0.96 (0.1) | 0.95 (0.1) | 0.081 | 0.96 (0.08) | 0.96 (0.1) | 0.66 | 0.58 |
BMI, kg/m2 | 32.4 (5.0) | 32.3 (4.8) | 0.74 | 32.1 (4.8) | 32.3 (5.0) | 0.078 | 0.18 |
SBP, mm Hg | 127.0 (10.7) | 128.8 (15.0) | 0.23 | 128.0 (11.9) | 126.6 (10.6) | 0.29 | 0.11 |
DBP, mm Hg | 80.3 (7.2) | 79.9 (9.9) | 0.25 | 79.8 (7.6) | 77.8 (8.4) | 0.032 | 0.53 |
Heart rate, beats/min | 74.7 (8.7) | 74.1 (8.2) | 0.59 | 73.2 (9.1) | 74.2 (9.8) | 0.17 | 0.17 |
Statin use, % | 34.9 | 30.9 | |||||
Diabetes, % | 39.5 | 35.0 | |||||
Fasting glucose, mg/dL | 120.1 (48.5) 3 | 125.4 (56.8) 3 | 0.39 | 119.4 (38.1) 3 | 127.5 (55.2) 3 | 0.0616 | 0.38 |
Fasting insulin, µIU/mL | 30.2 (41.3) 4 | 30.1 (35.8) 4 | 0.51 | 20.8 (18.2) 5 | 24.0 (24.3) 5 | 0.21 | 0.63 |
HbA1c, % | 6.5 (1.5) 6 | 6.6 (1.7) 6 | 0.67 | 6.3 (1.4) 7 | 6.3 (1.4) 7 | 0.83 | 0.87 |
Triglycerides, mg/dL | 199.1 (123.0) 2 | 185.7 (118.0) 2 | 0.52 | 192.0 (125.1) 5 | 157.8 (84.2) 5 | 0.0008 | 0.053 |
BUN, mg/dL | 14.7 (4.9) 2 | 15.0 (4.5) 2 | 0.88 | 15.4 (5.0) 5 | 16.2 (4.9) 5 | 0.25 | 0.46 |
Creatinine, mg/dL | 0.8 (0.2) 2 | 0.82 (0.2) 2 | 0.51 | 0.3 (0.2) 5 | 0.84 (0.2) 5 | 0.26 | 0.19 |
TSH µIU/mL | 1.9 (1.0) 2 | 2.5 (2.7) 2 | 0.025 | 1.7 (0.9) 7 | 1.8 (0.9) 7 | 0.043 | 0.86 |
Hs-CRP, mg/L | 6.4 (9.2) 2 | 5.5 (5.8) 2 | 0.46 | 8.1 (17.5) 8 | 6.7 (10.9) 8 | 0.75 | 0.82 |
Albumin, g/dL | 4.29 (0.3) 2 | 4.3 (0.3) 2 | 0.69 | 4.29 (0.3) 5 | 4.3 (0.3) 5 | 0.62 | 0.91 |
ALT, IU/L | 35.6 (24.0) | 29.8 (21.2) | 0.005 | 37.5 (39.0) | 38.1 (37.7) | 0.48 | 0.015 |
AST, IU/L | 25.8 (12.2) | 23.9 (13.5) | 0.036 | 27.1 (20.3) | 28.7 (24.6) | 0.37 | 0.036 |
ALP, IU/L | 81.5 (31.0) | 76.3 (21.5) | 0.01 | 85.5 (45.3) | 83.2 (40.3) | 0.09 | 0.73 |
GGT, IU/L | 47.1 (49.0) | 37.1 (32.2) | <.0001 | 62.2 (151.4) | 57.1 (108.7) | 0.37 | 0.058 |
Bilirubin, mg/dL | 0.5 (0.2) | 0.47 (0.2) | 0.70 | 0.5 (0.3) | 0.5 (0.2) | 0.88 | 0.72 |
Placebo (n = 86) | MF4637 (n = 81) | p-Value 1 | |||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | T = 12 weeks | T = 24 weeks | Change from Baseline | Baseline | T = 12 weeks | T = 24 weeks | Change from Baseline | ||
RBC omega-3 index, % | 4.9 (1.2) | 5.8 (1.3) | 5.3 (1.1) | 0.4 (1.0) | 4.8 (1.1) | 8.7 (2.3) | 8.0 (2.6) | 3.2 (2.7) | <0.0001 |
RBC EPA + DHA, µg/mL | 32.3 (26.4) | 34.9 (21.0) | 33.1 (20.5) | 1.2 (14.9) | 29.6 (17.5) | 51.5 (38.9) | 52.9 (40.7) | 21.2 (28.7) | <0.0001 |
RBC EPA, % | 0.54 (0.3) | 0.54 (0.2) | 0.54 (0.2) | 0.002 (0.3) | 0.53 (0.2) | 1.6 (0.9) | 1.4 (0.9) | 0.9 (1.0) | <0.0001 |
RBC EPA, µg/mL | 3.8 (6.6) | 3.7 (2.6) | 4.1 (5.7) | 0.4 (7.0) | 3.0 (2.6) | 10.4 (10.7) | 10.6 (12.0) | 7.1 (10.5) | <0.0001 |
RBC DHA, % | 4.3 (1.1) | 5.2 (1.2) | 4.8 (1.0) | 0.4 (0.9) | 4.3 (1.0) | 7.1 (1.5) | 6.6 (1.8) | 2.3 (1.9) | <0.0001 |
RBC DHA, µg/mL | 28.5 (21.0) | 31.2 (18.6) | 29.0 (16.2) | 0.7 (10.7) | 26.6 (15.3) | 41.0 (28.8) | 42.4 (29.8) | 14.1 (19.5) | <0.0001 |
RBC omega-6: omega-3 | 4.9 (1.1) | 4.5 (0.9) | 4.7 (0.8) | −0.2 (0.7) | 4.9 (1.2) | 3.0 (0.9) | 3.3 (1.5) | −1.6 (1.8) | <0.0001 |
Placebo 1 | MF4637 1 | p-Value | |||||||
---|---|---|---|---|---|---|---|---|---|
T = 0 weeks | T = 24 weeks | Change from Baseline | T = 0 weeks | T = 24 weeks | Change from Baseline | ||||
Absolute | Relative | Absolute | Relative | ||||||
Liver fat, % | 17.4 (10.4) | 12.6 (8.0) | −4.4 (6.9) | −27.6 | 14.4 (10.1) | 10.7 (7.6) | −2.8 (5.8) | −25.7 | 0.1838 |
Baseline HFF Mean (SD) | Study End HFF Mean (SD) | Change in MRI-PDFF Liver Fat Percentage (%) | |||||
---|---|---|---|---|---|---|---|
Absolute Change | p-Value 1 | Relative Change | p-Value 1 | ||||
FLI <30 2 | Placebo | 15.6 (11.2) | 11.2 (7.8) | 2.25 (1.39) | 0.11 | 2.7 (11.3) | 0.81 |
Omega-3 | 12.5 (8.6) | 10.3 (7.7) | |||||
FLI ≥30 3 | Placebo | 20.6 (9.4) | 16.0 (7.9) | −2.47 (2.53) | 0.34 | −9.3 (15.3) | 0.55 |
Omega-3 | 19.3 (11.1) | 13.5 (7.0) | |||||
FLI ≥40 4 | Placebo | 20.2 (9.5) | 16.3 (8.4) | −7.45 (2.81) | 0.02 | −44.1 (14.6) | 0.009 |
Omega-3 | 20.7 (10.4) | 10.6 (5.2) |
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Tobin, D.; Brevik-Andersen, M.; Qin, Y.; Innes, J.K.; Calder, P.C. Evaluation of a High Concentrate Omega-3 for Correcting the Omega-3 Fatty Acid Nutritional Deficiency in Non-Alcoholic Fatty Liver Disease (CONDIN). Nutrients 2018, 10, 1126. https://doi.org/10.3390/nu10081126
Tobin D, Brevik-Andersen M, Qin Y, Innes JK, Calder PC. Evaluation of a High Concentrate Omega-3 for Correcting the Omega-3 Fatty Acid Nutritional Deficiency in Non-Alcoholic Fatty Liver Disease (CONDIN). Nutrients. 2018; 10(8):1126. https://doi.org/10.3390/nu10081126
Chicago/Turabian StyleTobin, Derek, Merethe Brevik-Andersen, Yan Qin, Jacqueline K. Innes, and Philip C. Calder. 2018. "Evaluation of a High Concentrate Omega-3 for Correcting the Omega-3 Fatty Acid Nutritional Deficiency in Non-Alcoholic Fatty Liver Disease (CONDIN)" Nutrients 10, no. 8: 1126. https://doi.org/10.3390/nu10081126