A Placebo-Controlled Trial of a Proprietary Lipid-Lowering … · 2020. 5. 21. · A...
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A Placebo-Controlled Trial of a Proprietary Lipid-Lowering Nutraceutical Supplement in the Management of Dyslipidemia Mark Houston, 1 Robert Rountree, 2 Alan Miller, 2 Jacqueline Jacques, 2 Joseph Lamb, 3 Kathleen Head, 2 Stephen M. Phipps, 2 Shasha Meng, 4 Bodi Zhang 2 1. Hypertension Institute of Nashville, Saint Thomas Hospital, Vanderbilt University School of Medicine, Nashville, Tennessee 2. Thorne Research, Inc., Sandpoint, Idaho 3. Hypertension Institute of Nashville, Saint Thomas Hospital, Nashville, Tennessee 4. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts SUBJECT CODES: Clinical Studies, Lipids and Cholesterol This study was designed to determine the tolerability and overall effectiveness of a proprietary multi-ingredient, lipid-lowering supplement in subjects with dyslipidemia. Aims Method 40 subjects were recruited for a single-center, double-blind, randomized, placebo-controlled trial. Study participants were recruited between December 2014 and March 2015. Initial screening included taking a medical history, physical examination, renal and hepatic function, serum lipid concentrations, serum electrolytes, complete blood counts, and urine analysis. The study’s 40 patients were randomly assigned to receive either the proprietary multi-ingredient lipid-lowering supplement (PMILLS) or placebo. The trial consisted of a screening visit, a two-week run-in, and a four-month treatment period. Samples were taken at baseline, one month, and four months of treatment. Primary Outcomes Secondary Outcomes Diastolic blood pressure decreased from 72.4 ± 9 mmHg to 68.1 ± 11 mmHg in the PMILLS group, while increasing from 72.3 ± 8 mmHg to 73.9 ± 9 mmHg with placebo (p=0.047) (see Table 2). Supplementation with the PMILLS group was also associated with decreased heart rate, from 67.5 ± 6 to 62.4 ± 7 (p=0.0093), which was significantly lower compared to the placebo group (see Table 1). TNF-α, hs-CRP, and IL-6 were measured in serum. In the PMILLS group, participants with the highest inflammatory markers at baseline showed the greatest response to intervention, which was highly significant (hs-CRP; p<0.001: TNF-α; p<0.001: IL-6; p<0.001) (see Figure 3). These effects were not observed in the placebo group. Safety Two of the recognized sides effects related to HMG-CoA inhibitor- based therapy are myopathy and serum coenzyme Q10 (CoQ10) reduction. None of the study participants reported any symptoms of myalgias or myopathy. There was also no significant reduction in serum CoQ10 levels at any time during the proprietary multi-ingredient lipid- lowering supplement group compared to the control group. (see Figure 4). Discussion This PMILLS appears to be a safe and effective nutritional supplement for the management of dyslipidemia and its attendant inflammation. It offers an excellent alternative to individuals who are statin intolerant or who refuse to take statins or other lipid-lowering drugs. This PMILLS significantly reduced all of the atherogenic particles implicated in CHD, such as LDL, LDL-P, Apo-lipoprotein B, VLDL, TG and oxLDL. LDL and LDL-P, the driving risks for CHD (6)(10), both achieved significant reductions of 19.5 percent (p<0.001) and 5.0 percent (p=0.0492), respectively, with the PMILLS at one and four months. Patients were screened for the study 68 Patients were randomized Proprietary Lipid Supplement group 20 patients randomized Placebo group 20 patients randomized 40 20 20 Treatment for 4 months Proprietary Lipid Supplement group 20 patients completed Placebo group 20 patients completed 20 20 FIGURE 4 TABLE 1 Before Baseline-4 mos Baseline-4 mos After P Value b Before After P Value b P Value a No. (Male/Female) 20 (8/12) 20 (10/10) Age (Yr) 62 + 6 58 + 7 Body Weight (lb) 168.4 + 26.5 165.3 + 24.7 0.87 170.2 + 31.5 171.4 + 29.7 0.79 0.84 BMI 26.76 + 2.41 26.49 + 2.53 0.91 26.98 + 3.05 27.01 +2.99 0.81 0.75 Systolic blood pressure (mm Hg) 135.7 + 4.92 130.9 + 3.92 0.098 136.6 + 4.57 135.1 + 5.72 0.82 0.41 Diastolic blood pressure (mm Hg) 72.3 + 2.09 69.4 + 1.79 0.001 75.05 + 2.01 74.78 + 2.14 0.79 0.04 Heart rate (bpm) 66.5 + 2.24 63 + 1.99 0.001 67.5 + 3.1 70.8 + 2.4 0.38 0.009 HbA1C(%) Baseline CRP Coefficients - 0.0291 - 0.9203 P-values 0.9117 < 0.0001 5.59 + 0.41 5.63 + 0.62 0.92 5.81 + 0.57 5.77 + 0.48 0.65 0.69 PROPRIETARY LIPID SUPPLEMENT PLACEBO Baseline and 4-month clinical characteristics of the proprietary lipid supplement and placebo groups FIGURE 3 Pearson Correlation Baseline vs 1 mos 1 mos vs 4 mos 1 mos vs 4 mos Baseline vs 4 mos Baseline vs 4 mos Baseline vs 1 mos Baseline TNFA Coefficients - 0.4837 - 0.8531 P-values 0.0359 - 0.1315 0.5917 - 0.5861 0.0084 - 0.8946 <0.0001 0.1959 0.4216 < 0.0001 Baseline vs 1 mos 1 mos vs 4 mos 1 mos vs 4 mos Baseline vs 4 mos Baseline vs 4 mos Baseline vs 1 mos Baseline IL-6 Coefficients 0.0503 - 0.9915 P-values 0.8381 - 0.3666 0.1227 - 0.3574 0.1331 < 0.9952 < 0.0001 0.0728 0.7672 < 0.0001 CONTROL PROPRIETARY LIPID SUPPLEMENT Baseline Base - 1 mos Base - 4 mos 1 mos – 4 mos hsCRP_0 delta_CRP_02 delta_CRP_24 delta_CRP_04 Baseline Base - 1 mos Base - 4 mos 1 mos – 4 mos hsCRP_0 delta_CRP_02 delta_CRP_24 delta_CRP_04 hsCRP_0 CONTROL PROPRIETARY LIPID SUPPLEMENT CONTROL PROPRIETARY LIPID SUPPLEMENT Baseline Base - 1 mos Base - 4 mos 1 mos – 4 mos Baseline Base - 1 mos 1 mos – 4 mos TNFA_0 delta_TNFA_02 delta_TNFA_24 delta_TNFA_04 TNFA_0 delta_TNFA_02 delta_TNFA_24 delta_TNFA_04 TNFA_0 TNFA_0 Int17A_0 Int17A_0 delta_INT17A_02 delta_INT17A_24 delta_INT17A_04 Int17A_0 delta_INT17A_02 delta_INT17A_24 delta_INT17A_04 Baseline Base - 1 mos Base - 4 mos 1 mos – 4 mos Baseline Base - 1 mos Base - 4 mos 1 mos – 4 mos Base - 4 mos Bodi Zhang [email protected] Thorne Research, Inc. P.O. Box 25 Dover, ID 83825 Tel: 208.263.1337 Fax: 800.747.1950 Mark Houston [email protected] Hypertension Institute 4230 Harding Road Saint Thomas Medical Plaza, Suite 400 Nashville, TN 37205 a= between group comparisons; b= within group comparisons; Red text indicates statistical significance p< 0.05 21.61 26.58 26.1 27.94 15.84 18.05 * * VLDL-C 10 15 20 25 30 Compared to the participants who received placebo, those receiving the PMILLS, had significant reductions in total cholesterol, LDL-C, and VLDL-C at both one and four months (see Figures 1,2, and 3). LDL-P decreased at four months in the PMILLS group, while no change was observed in the placebo group. Total LDL-III and IV particle number (LDL-P), an important indicator of LDL particle size. After treatment, oxLDL was significantly decreased in the PMILLS group, whereas, no change was observed in the placebo group (see Figure 4). Similar between-group changes were also observed for Apo-lipoprotein B and triglycerides (see Figures 5 and 6). 80 Baseline 1 mos 4 mos 90 100 110 120 130 140 150 160 144.05 142.02 146.84 140.2 106.2 117.9 * Apo-lipoprotein B Control Proprietary Lipid Supplement Control Proprietary Lipid Supplement Control Proprietary Lipid Supplement Control Proprietary Lipid Supplement 80 100 120 140 160 180 200 Baseline 1 mos 4 mos 131 158.35 173.16 162.84 117.05 120.85 * * Triglycerides Control Proprietary Lipid Supplement OxLDL 30 35 40 45 50 55 60 55.95 * 51.65 42.7 42.6 53.75 162.84 Baseline 1 mos 4 mos 200 Baseline 1 mos 4 mos 210 220 230 240 250 260 270 246.45 242.55 226.55 214.16 256.68 258.58 Total Cholesterol 100 Baseline 1 mos 4 mos Control Proprietary Lipid Supplement Baseline 1 mos 4 mos 120 110 140 130 150 170 160 180 190 200 164.1 166.2 139.15 133.73 169.9 165.9 LDL-C FIGURE 2 FIGURE 1 FIGURE 2 FIGURE 1 FIGURE 3 FIGURE 5 FIGURE 4 FIGURE 6
Transcript of A Placebo-Controlled Trial of a Proprietary Lipid-Lowering … · 2020. 5. 21. · A...
A Placebo-Controlled Trial of a Proprietary Lipid-LoweringNutraceutical Supplement in the Management of DyslipidemiaMark Houston,1 Robert Rountree,2 Alan Miller,2 Jacqueline Jacques,2 Joseph Lamb,3 Kathleen Head,2 Stephen M. Phipps,2 Shasha Meng,4 Bodi Zhang2
1. Hypertension Institute of Nashville, Saint Thomas Hospital, Vanderbilt University School of Medicine, Nashville, Tennessee
2. Thorne Research, Inc., Sandpoint, Idaho
3. Hypertension Institute of Nashville, Saint Thomas Hospital, Nashville, Tennessee
4. Department of Epidemiology, Harvard School of Public Health, Boston,
Massachusetts
SUBJECT CODES: Clinical Studies, Lipids and Cholesterol
This study was designed to determine the tolerability and overall e�ectiveness of a proprietary multi-ingredient, lipid-lowering supplement in subjects with dyslipidemia.
Aims
Method40 subjects were recruited for a single-center, double-blind, randomized, placebo-controlled trial. Study participants were recruited between December 2014 and March 2015. Initial screening included taking a medical history, physical examination, renal and hepatic function, serum lipid concentrations, serum electrolytes, complete blood counts, and urine analysis.
The study’s 40 patients were randomly assigned to receive either the proprietary multi-ingredient lipid-lowering supplement (PMILLS) or placebo. The trial consisted of a screening visit, a two-week run-in, and a four-month treatment period.
Samples were taken at baseline, one month, and four months of treatment.
Primary Outcomes
Secondary OutcomesDiastolic blood pressure decreased from 72.4 ± 9 mmHg to 68.1 ± 11 mmHg in the PMILLS group, while increasing from 72.3 ± 8 mmHg to 73.9 ± 9 mmHg with placebo (p=0.047) (see Table 2). Supplementation with the PMILLS group was also associated with decreased heart rate, from 67.5 ± 6 to 62.4 ± 7 (p=0.0093), which was significantly lower compared to the placebo group (see Table 1).
TNF-α, hs-CRP, and IL-6 were measured in serum. In the PMILLS group, participants with the highest inflammatory markers at baseline showed the greatest response to intervention, which was highly significant (hs-CRP; p<0.001: TNF-α; p<0.001: IL-6; p<0.001) (see Figure 3). These e�ects were not observed in the placebo group.
SafetyTwo of the recognized sides e�ects related to HMG-CoA inhibitor- based therapy are myopathy and serum coenzyme Q10 (CoQ10) reduction. None of the study participants reported any symptoms of myalgias or myopathy. There was also no significant reduction in serum CoQ10 levels at any time during the proprietary multi-ingredient lipid- lowering supplement group compared to the control group. (see Figure 4).
DiscussionThis PMILLS appears to be a safe and e�ective nutritional supplement for the management of dyslipidemia and its attendant inflammation. It o�ers an excellent alternative to individuals who are statin intolerant or who refuse to take statins or other lipid-lowering drugs. This PMILLS significantly reduced all of the atherogenic particles implicated in CHD, such as LDL, LDL-P, Apo-lipoprotein B, VLDL, TG and oxLDL. LDL and LDL-P, the driving risks for CHD (6)(10), both achieved significant reductions of 19.5 percent (p<0.001) and 5.0 percent (p=0.0492), respectively, with the PMILLS at one and four months.
Patients were screenedfor the study
68
Patients were randomized
Proprietary Lipid Supplement group 20 patients randomized
Placebo group 20 patientsrandomized
40
20 20Treatment for4 months
Proprietary Lipid Supplement group 20 patients completed
Placebo group 20 patientscompleted
20 20
FIGURE 4
TABLE 1
Before
Baseline-4 mos Baseline-4 mos
After P Valueb Before After P Valueb P Valuea
No. (Male/Female) 20 (8/12) 20 (10/10)
Age (Yr) 62 + 6 58 + 7
Body Weight (lb) 168.4 + 26.5 165.3 + 24.7 0.87 170.2 + 31.5 171.4 + 29.7 0.79 0.84
BMI 26.76 + 2.41 26.49 + 2.53 0.91 26.98 + 3.05 27.01 +2.99 0.81 0.75
Systolic blood pressure (mm Hg) 135.7 + 4.92 130.9 + 3.92 0.098 136.6 + 4.57 135.1 + 5.72 0.82 0.41
Diastolic blood pressure (mm Hg) 72.3 + 2.09 69.4 + 1.79 0.001 75.05 + 2.01 74.78 + 2.14 0.79 0.04
Heart rate (bpm) 66.5 + 2.24 63 + 1.99 0.001 67.5 + 3.1 70.8 + 2.4 0.38 0.009
HbA1C(%)
Baseline CRP Coe�cients - 0.0291 - 0.9203
P-values 0.9117 < 0.0001
5.59 + 0.41 5.63 + 0.62 0.92 5.81 + 0.57 5.77 + 0.48 0.65 0.69
PROPRIETARY LIPID SUPPLEMENT PLACEBO
Baseline and 4-month clinical characteristics of the proprietary lipid supplement and placebo groups
FIGURE 3
Pearson Correlation
Baseline vs 1 mos 1 mos vs 4 mos 1 mos vs 4 mos Baseline vs 4 mos Baseline vs 4 mos Baseline vs 1 mos
Baseline TNFA Coe�cients - 0.4837 - 0.8531
P-values 0.0359
- 0.1315
0.5917
- 0.5861
0.0084
- 0.8946
<0.0001
0.1959
0.4216 < 0.0001
Baseline vs 1 mos 1 mos vs 4 mos 1 mos vs 4 mos Baseline vs 4 mos Baseline vs 4 mos Baseline vs 1 mos
Baseline IL-6 Coe�cients 0.0503 - 0.9915
P-values 0.8381
- 0.3666
0.1227
- 0.3574
0.1331
< 0.9952
< 0.0001
0.0728
0.7672 < 0.0001
CONTROL PROPRIETARY LIPID SUPPLEMENT
Baseline Base - 1 mos Base - 4 mos1 mos – 4 mos
hsCRP_0 delta_CRP_02 delta_CRP_24 delta_CRP_04
Baseline Base - 1 mos Base - 4 mos1 mos – 4 mos
hsCRP_0 delta_CRP_02 delta_CRP_24 delta_CRP_04
hsCR
P_0
CONTROL PROPRIETARY LIPID SUPPLEMENT
CONTROL PROPRIETARY LIPID SUPPLEMENT
Baseline Base - 1 mos Base - 4 mos1 mos – 4 mos Baseline Base - 1 mos 1 mos – 4 mos
TNFA_0 delta_TNFA_02 delta_TNFA_24 delta_TNFA_04 TNFA_0 delta_TNFA_02 delta_TNFA_24 delta_TNFA_04
TNFA
_0
TNFA
_0
Int1
7A_0
Int17A_0 delta_INT17A_02 delta_INT17A_24 delta_INT17A_04 Int17A_0 delta_INT17A_02 delta_INT17A_24 delta_INT17A_04
Baseline Base - 1 mos Base - 4 mos1 mos – 4 mos Baseline Base - 1 mos Base - 4 mos1 mos – 4 mos
Base - 4 mos
Bodi [email protected] Research, Inc.P.O. Box 25Dover, ID 83825Tel: 208.263.1337Fax: 800.747.1950
Mark [email protected] Institute4230 Harding RoadSaint Thomas Medical Plaza,Suite 400Nashville, TN 37205
a= between group comparisons; b= within group comparisons; Red text indicates statistical signi�cance p< 0.05
21.61
26.58
26.1
27.94
15.84
18.05
**
VLDL-C
10
15
20
25
30
Compared to the participants who received placebo, those receiving the PMILLS, had significant reductions in total cholesterol, LDL-C, and VLDL-C at both one and four months (see Figures 1,2, and 3). LDL-P decreased at four months in the PMILLS group, while no change was observed in the placebo group. Total LDL-III and IV particle number (LDL-P), an important indicator of LDL particle size. After treatment, oxLDL was significantly decreased in the PMILLS group, whereas, no change was observed in the placebo group (see Figure 4). Similar between-group changes were also observed for Apo-lipoprotein B and triglycerides (see Figures 5 and 6).
80Baseline 1 mos 4 mos
90
100
110
120
130
140
150
160
144.05
142.02
146.84
140.2
106.2117.9
*
Apo-lipoprotein B
Control Proprietary Lipid SupplementControl Proprietary Lipid Supplement
Control Proprietary Lipid Supplement Control Proprietary Lipid Supplement
80
100
120
140
160
180
200
Baseline 1 mos 4 mos
131
158.35
173.16
162.84
117.05120.85
**
Triglycerides
Control Proprietary Lipid Supplement
OxLDL
30
35
40
45
50
55
6055.95
*51.65
42.7 42.6
53.75162.84
Baseline 1 mos 4 mos
200Baseline 1 mos 4 mos
210
220
230
240
250
260
270
246.45
242.55
226.55
214.16
256.68 258.58
Total Cholesterol
100Baseline 1 mos 4 mos
Control Proprietary Lipid Supplement
Baseline 1 mos 4 mos
120
110
140
130
150
170
160
180
190
200
164.1
166.2
139.15133.73
169.9 165.9
LDL-CFIGURE 2 FIGURE 1 FIGURE 2 FIGURE 1 FIGURE 3
FIGURE 5FIGURE 4 FIGURE 6
