| OBJECTIVE:The investigation focuses on the evaluation of functional effects of 2 fish oil preparations in the subjects with dyslipidemia by 2 independent clinical trials. The attempt was aimed to find effectof fish oilon human blood lipids metabolismand any potential difference between the two fish oil preparations with the different ratio of EPA and DHA in the effects on lipid profile by pooling the results from the 2 trials, to seek more solid scientific evidence for practical guideline related to the improvement of blood lipid profile for the prevention and treatment of dyslipidemia and the reduction of the risk of its relevant cardiovascular diseases.METHODS:In each of the 2 randomized, parallel, blank control studies, conducted respectively in one community in Shanghai, one-hundred-twenty(120)subjects with dyslipidemia were enrolled and randomly assignedto receive oral fish oil preparation or blank control group at ratio of 1:1. The fish oil group regimens were daily 4 of 1000mg fish oil preparation (Capsule I, each containing 175mg EPA and 70mg DHA) for Study 1, and daily 3 of 1500mg fish oil preparation (Capsule II, each containing 197mg EPA and 131mg DHA) for Study 2, respectively, each group taking continuously for 45 days. The primary effect measurement is the proportion of the subjects with greater than 10% reduction in serum total cholesterol (TC) and more than 15% reduction in serum triglyceride (TG), compared with the baseline. The other effect measurements include the proportion of subjects having eitherreduction of TC more than 10% or TG more than 15%, and the percentage changes of TC and TG after the intervention for 45 days. For the binomial data, Pearson’s Chi-square test was employed to the significant analysis of the differences between the fish oil group and blank control group. For the continuous data, i.e. the percentage changes after treatment from baseline in lipid profile, student’s t-test or Wilcoxon Rank Sum test was used to analyze the significance of differences between the 2 groups, based on the data distributions. To evaluate the overall effect of oil fish preparations, Meta-analysis approach for the proportion difference were applied. The type I error margin for all the significant analyses was 0.05.RESULTS:At the end of the trials,20 subjects in each study did not return for study evaluation, and thus they were not included for the analyses and evaluations. Therefore, there were 100 subjects,50 in each of fish oil and blank control group in each trials for analyses.At baseline, all the subjects in analyses set had higher TC (more than 5.2 mmol/L) and TG (greater than 1.65 mmol/L). In the 2 trials, the subjects with reduction of TC more than 10% and TG more than 15% were20 (40%) for Study 1, and 16 (32%) for Study 2, respectively, in the administration of fish oil preparations (Capsule I or Capsule II), but in the subjects receiving blank as control, there were only 4 subjects (8%) for Study 1 and 0 subject for Study 2, respectively, achieving the target. In Study 1, the proportion of overall effect was approximately 32%, significantly higher in Capsule I than blank control group (p= 0.0002). Similarly, in the Study 2, the proportion of subjects achieving the target in Capsule II was 32%, significantly higher comparing to the blank control group (p<0.0001).InStudy 1, after the daily oral administration of 4 of Capsule I continuously for 45 days, mean TC level in subjects receiving Capsule I was changed from 5.74±0.452 mmol/Lof baseline to 5.07±0.663 mmol/L of the end of study and the median percentage change was -11.54%. In the subjects in blank control group, the TC level was changed from 5.70±0.475 mmol/L to5.64±0.830mmol/L, the median percentage change was -0.50%. The Capsule I induced TC change was significantly more than that in blank control and the difference was estimated-11.7%(p< 0.0001). In the Study 2, the mean change of TC level from baseline were-10.4±13.85% for daily 3 of Capsule Ⅱ and0.6±8.08% for the blank control group. The difference of Capsule II from blank control in TC change percent was-11.0%(p< 0.0001). Correspondingly, the greater benefits in reduction of TC level in fish oil supplementation in the 2 studies could be translated to the greater proportion of subjects achieving the target of more than 10%in TC:In Study 1, the proportion of the subjects treated with Capsule I was 48%(p< 0.0001)significantly higher than the blank control, and in Study 2, the difference of Capsule II in the proportion achieving the target was 42%(p< 0.0001) from the blank control.For the TG profile, in the Study 1, the subjects daily receiving 4 of capsule I for 45 days had serum TC level changed from 2.58±1.099 mmol/Lof the baseline to 1.89± 0.797 mmol/Lof the end of the study, and the median of TG percentage change was-21.2% in the control group, the mean TG level was changed from 2.41±0.864 mmol/L of the baseline to 2.43±1.130mmol/Lof the end of the study, and the median of TG percentage change was -3.09%. By comparison between groups, Capsule I induced greater reduction in TG profile than blank control group, achieving approximately -24.3%(p=0.0006 by Satterthwaite approximate t-test).In the Study 2, the changes in TG level of the subjects with Capsule II supplementation was from2.47±1.151 mmol/L before the administration to 1.97±1.259 mmol/Lin the end of study, and median percentage change was -29.55%. But in the blank control group, the mean TG level was 2.50±1.085mmol/L at the baseline and 2.46±0.956mmol/L in the end of study, respectively, and median percentage change was -0.11%. By comparing the percentage changes of TG profile in the two test groups, Capsule II produced more decrease in TG level, the deviation of Capsule II supplementation from the control group in TG profile was estimated -29.01%(p=0.0003). For the subjects with TG reduction more than 15% from, there were 31 subjects (62.0%) in the Study 1, Capsule Iadministration and 33 subjects (66.0%) in the Study 2, Capsule Ⅱadministration, respectively; and in the control group, the subjects achieving the target were 15 (30%) for the Study 1 and 11 (22%) for the Study 2, respectively.Obviously, the proportion achieving the target in the subjects associated with fish oil supplementation were 32%(p= 0.0013) for Study 1 and 44%(p< 0.0001) for the Study 2, respectively, higher than the blank control ones.On the HDL-C level changes, in the Study 1, the subjects with Capsule I had the changes of median HDL-C level from 1.425 mmol/Lof the baseline to 1.455 mmol/L in the study end, and median change was -0.025mmol/L; and the subjects in the blank control group, themedian HDL-C level was changed from 1.46 mmol/L of the baseline to 1.355mmol/L in the end of the study, and the median changing was 0.065 mmol/L. The difference of oral Capsule I from the blank control one was estimated 0.0650 mmol/L by Hodges-Lehmann method, and did not have significance (p= 0.0581 by Wilcoxon Rank Sum test). In Study 2, daily 3 of Capsule II for 45 days had the mean HDL-C level changed from 1.45±0.310 mmol/L of the baseline to 1.40±0.341 mmol/Lat the end of study, and in the control group, the mean HDL-C level in the subject was changed was from 1.37±0.226 to 1.34±0.255 mmol/L. The mean changes were -0.050±0.2669 mmol/Lfor Capsule II and -0.035±0.1889 mmol/L for the blank control group, respectively. There was no significant difference between the two groups in the HDL-C changes (mean difference:-0.0154 mmol/L, p=0.7399, by Satterthwaite approximate t-test).By pooling the results from the 2 trials, no evidence was found to demonstrate any difference in the modification of serum lipid profile by the two fish oil preparations with different EPA/DHA ratio.In the 2 studies, No adverse events was reported, and all the laboratory results related to the safety profiles were comparable between the baseline and the end of study.CONCLUSIONSThe study concludes that fish oil could have positive effects on human blood lipids metabolismby significantly declining the level of TC and TG; however, there is no changes in normal level of HDL-C and no evidence to show the effect difference between the fish oil capsules with different EPA/DHA ratio. The results from the two studies suggests that administration of fish oil preparations with n-3 unsaturated fattyacid as a supplementation could be favor for the prevention and treatment of adult dyslipidemia, and thus reduce the potential risk of cardiovascular diseases. |
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