Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation

Figures & data

Figure 1 Subject disposition.

Notes: *Two subjects withdrew from the study due to adverse events, and one moved out of the city. The adverse events that were reported were: cold symptoms (n=1); and presence of blood in the stool (n=1). **Four subjects withdrew from the study due to adverse events. The adverse events that were reported were: LDL-C increased to ATP III high-risk category (n=3); and one subject did not wish to continue study after being ill with strep throat (n=1). ***One subject withdrew from the study due to an increase in LDL-C to ATP III high-risk category. The black boxes represent the pantethine tablets which was the investigational product and the white boxes represent the placebo. In order to maintain blinding all subjects received 3 tablets. At week 8 the dose was increased in the pantethine group so they received three pantethine tablets (three black boxes).
Abbreviations: ATP III, Adult Treatment Panel III (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in adults); LDL-C, low-density lipoprotein cholesterol; TLC, Therapeutic Lifestyle Change.

Table 1 Baseline physical characteristics of participants in the pantethine and placebo groups

Characteristic	Pantethine (n=16) mean ± SD	Placebo (n=16) mean ± SD	P-valuea
Age (years)	54.4±7.3	47.2±12.1	0.051
Height (cm)	164.8±6.9	169.3±7.5	0.083
Sex (%)
Female	87.50	56.25	0.113
Male	12.50	43.75
Race (%)
White	87.50	93.75	>0.999
Other	12.50	6.25	>0.999

Notes:

a Between-group (adjusted to baseline) statistical comparisons were conducted using unpaired t-test. Probability values P<0.05 are significant.

Abbreviation: SD, standard deviation.

Figure 2 Changes in the serum (A) TC, (B) LDL-C, (C) non-HDL-C, and (D) Apo-B levels at screening, baseline, and weeks 2, 4, 8, 12 and 16 of the study period.

Notes: Data are represented as the mean ± SEM. Triangle (▲) represents placebo, and square (■) represents pantethine. Asterisk (*) indicates a statistically significant (P<0.05) between-group statistical comparison, using baseline as a covariate.
Abbreviations: Apo-B, apolipoprotein B; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol; SEM, standard error of the mean; TC, total cholesterol.

Table 2 Biochemistry and clinical characteristics of participants in the pantethine and placebo groups

	Pantethine	Placebo	P-value
	(n) mean ± SD	(n) mean ± SD
Hemoglobin (g/L)
Screening	(16) 139.90±5.90	(16) 144.60±13.30	–
Baseline	(16) 138.40±6.10	(16) 140.90±11.30	0.508
Week 2	(16) 138.40±7.20	(16) 141.90±12.20	0.339
Week 4	(16) 137.10±8.30	(16) 141.60±10.70	0.201
Week 8 dose escalation	(16) 136.50±9.50	(13) 141.20±12.70	0.260
Week 12	(15) 135.50±9.30	(9) 141.00±13.60	0.253
Week 16 end of study	(15) 134.60±8.20	(9) 142.20±13.00	0.090
Hematocrit (L/L)
Screening	(16) 0.408±0.020	(16) 0.422±0.039	–
Baseline	(16) 0.406±0.023	(16) 0.415±0.036	0.412
Week 2	(16) 0.406±0.027	(16) 0.414±0.032	0.444
Week 4	(16) 0.403±0.028	(16) 0.414±0.031	0.289
Week 8 dose escalation	(16) 0.402±0.032	(13) 0.414±0.036	0.357
Week 12	(15) 0.400±0.041	(9) 0.414±0.044	0.428
Week 16 end of study	(15) 0.402±0.039	(9) 0.424±0.039	0.184
White blood cells (10^9/L)
Screening	(16) 6.19±1.52	(16) 7.14±2.31	–
Baseline	(16) 5.86±1.10	(16) 6.46±1.85	0.273
Week 2	(16) 5.96±1.33	(16) 6.29±2.30	0.821
Week 4	(16) 6.02±0.89	(16) 6.51±2.27	0.533
Week 8 dose escalation	(16) 5.83±1.19	(13) 6.54±1.84	0.218
Week 12	(15) 5.68±1.48	(9) 5.87±2.37	0.530
Week 16 end of study	(15) 5.89±1.58	(9) 6.10±2.08	0.835
Red blood cells (10^12/L)
Screening	(16) 4.52±0.28	(16) 4.70±0.47	–
Baseline	(16) 4.45±0.23	(16) 4.61±0.38	0.173
Week 2	(16) 4.46±0.31	(16) 4.59±0.36	0.293
Week 4	(16) 4.40±0.28	(16) 4.59±0.35	0.115
Week 8 dose escalation	(16) 4.40±0.32	(13) 4.57±0.36	0.189
Week 12	(15) 4.37±0.37	(9) 4.63±0.32	0.087
Week 16 end of study	(15) 4.35±0.30	(9) 4.71±0.30	0.011*
MCV (fL)
Screening	(16) 90.50±2.70	(16) 90.10±3.70	–
Baseline	(16) 91.30±3.00	(16) 89.90±3.40	0.242
Week 2	(16) 91.20±3.10	(16) 90.10±3.80	0.401
Week 4	(16) 91.20±3.20	(16) 90.40±3.90	0.525
Week 8 dose escalation	(16) 91.50±3.30	(13) 90.80±4.60	0.626
Week 12	(15) 91.90±3.80	(9) 89.30±4.80	0.162
Week 16 end of study	(15) 92.00±4.50	(9) 90.00±5.30	0.332
MCH (pg)
Screening	(16) 31.02±1.18	(16) 30.76±1.67	–
Baseline	(16) 31.14±1.16	(16) 30.66±1.40	0.292
Week 2	(16) 31.07±1.15	(16) 30.96±1.49	0.813
Week 4	(16) 31.18±1.15	(16) 30.97±1.74	0.687
Week 8 dose escalation	(16) 31.07±1.25	(13) 30.95±1.81	0.831
Week 12	(15) 31.10±1.18	(9) 30.37±1.53	0.199
Week 16 end of study	(15) 31.02±1.13	(9) 30.10±1.49	0.100
MCH concentration (g/L)
Screening	(16) 342.50±5.80	(16) 341.70±6.10	–
Baseline	(16) 341.30±8.60	(16) 340.60±6.90	0.570
Week 2	(16) 340.90±8.90	(16) 343.40±7.60	0.387
Week 4	(16) 341.80±6.60	(16) 342.00±8.10	0.943
Week 8 dose escalation	(16) 339.60±7.90	(13) 341.00±8.90	0.648
Week 12	(15) 339.10±15.20	(9) 341.00±14.30	0.698
Week 16 end of study	(15) 337.10±14.80	(9) 334.90±13.50	0.611
RDW (%)
Screening	(16) 13.55±0.75	(16) 13.59±0.97	–
Baseline	(16) 13.76±0.94	(16) 13.73±1.03	0.663
Week 2	(16) 13.82±0.85	(16) 13.81±1.06	0.971
Week 4	(16) 13.84±0.92	(16) 13.86±1.11	0.945
Week 8 dose escalation	(16) 13.98±1.05	(13) 13.64±1.20	0.262
Week 12	(15) 13.97±1.23	(9) 13.96±1.23	>0.999
Week 16 end of study	(15) 14.09±1.16	(9) 14.08±1.36	0.952
Platelet count (10^9/L)
Screening	(16) 302.00±66.00	(16) 276.00±79.00	–
Baseline	(15) 285.00±59.00	(16) 260.00±67.00	0.287
Week 2	(16) 293.00±61.00	(16) 262.00±78.00	0.222
Week 4	(16) 284.00±68.00	(16) 263.00±70.00	0.346
Week 8 dose escalation	(16) 282.00±68.00	(13) 273.00±81.00	0.735
Week 12	(15) 272.00±62.00	(9) 247.00±79.00	0.221
Week 16 end of study	(15) 267.00±67.00	(9) 269.00±96.00	0.907
MPV (fL)
Screening	(16) 8.37±0.81	(16) 8.99±0.88	–
Baseline	(15) 8.57±1.10	(16) 9.04±0.91	0.208
Week 2	(16) 8.49±0.83	(16) 9.14±0.77	0.028*
Week 4	(16) 8.52±0.86	(16) 9.22±0.91	0.032*
Week 8 dose escalation	(16) 8.54±0.76	(13) 9.05±0.65	0.063
Week 12	(15) 8.63±0.93	(9) 8.97±0.43	0.436
Week 16 end of study	(15) 8.66±0.94	(9) 9.04±0.55	0.353
Neutrophils (10^9/L)
Screening	(16) 3.57±1.07	(16) 4.62±1.93	–
Baseline	(16) 3.47±0.91	(16) 3.94±1.36	0.257
Week 2	(16) 3.46±0.99	(16) 3.96±1.87	0.706
Week 4	(16) 3.65±0.71	(16) 4.14±1.75	0.307
Week 8 dose escalation	(16) 3.41±1.00	(13) 4.17±1.46	0.106
Week 12	(15) 3.30±1.36	(9) 3.58±1.43	0.676
Week 16 end of study	(14) 3.33±1.03	(9) 3.60±1.24	0.567
Lymphocytes (10^9/L)
Screening	(16) 1.99±0.51	(16) 1.90±0.51	–
Baseline	(16) 1.87±0.44	(16) 1.94±0.53	0.714
Week 2	(16) 1.90±0.53	(16) 1.73±0.47	0.345
Week 4	(16) 1.79±0.40	(16) 1.82±0.51	0.878
Week 8 dose escalation	(16) 1.86±0.39	(13) 1.82±0.51	0.817
Week 12	(15) 1.79±0.63	(9) 1.74±0.85	0.474
Week 16 end of study	(14) 2.07±1.04	(9) 1.90±0.94	0.378
Monocytes (10^9/L)
Screening	(16) 0.40±0.14	(16) 0.42±0.14	–
Baseline	(16) 0.34±0.13	(16) 0.39±0.12	0.350
Week 2	(16) 0.37±0.13	(16) 0.39±0.11	0.651
Week 4	(16) 0.38±0.09	(16) 0.37±0.10	0.816
Week 8 dose escalation	(16) 0.35±0.12	(13) 0.38±0.10	0.507
Week 12	(15) 0.36±0.13	(9) 0.36±0.16	0.591
Week 16 end of study	(14) 0.38±0.12	(9) 0.33±0.14	0.403
Eosinophils (10^9/L)
Screening	(16) 0.19±0.14	(16) 0.16±0.12	–
Baseline	(16) 0.15±0.10	(16) 0.15±0.14	0.955
Week 2	(16) 0.19±0.12	(16) 0.16±0.19	0.375
Week 4	(16) 0.18±0.13	(16) 0.16±0.14	0.748
Week 8 dose escalation	(16) 0.17±0.14	(13) 0.16±0.12	0.775
Week 12	(15) 0.22±0.19	(9) 0.17±0.19	0.550
Week 16 end of study	(14) 0.17±0.13	(9) 0.22±0.17	0.481
Basophils (10^9/L)
Screening	(16) 0.050±0.028	(16) 0.034±0.033	–
Baseline	(16) 0.041±0.030	(16) 0.028±0.038	0.472
Week 2	(16) 0.049±0.032	(16) 0.037±0.035	0.157
Week 4	(16) 0.035±0.029	(16) 0.041±0.036	0.583
Week 8 dose escalation	(16) 0.033±0.031	(13) 0.032±0.034	0.890
Week 12	(15) 0.023±0.026	(9) 0.026±0.025	0.897
Week 16 end of study	(14) 0.025±0.032	(9) 0.059±0.051	0.090
Glucose (mmol/L)
Screening/baseline	(16) 4.83±0.71	(16) 4.98±0.53	0.677
Creatinine (μmol/L)
Screening/baseline	(16) 66.20±12.20	(16) 75.90±15.00	0.054
Week 16 end of study	(16) 65.50±11.90	(14) 74.50±13.00	0.058
eGFR (mL/min/1.73 m^2)
Screening/baseline	(16) 84.90±7.20	(16) 85.10±6.80	0.787
Week 16 end of study	(16) 85.80±6.90	(14) 86.60±6.00	0.588
AST (U/L)
Screening	(16) 20.50±6.20	(16) 24.70±10.80	–
Baseline	(16) 19.40±3.90	(16) 22.90±7.80	0.198
Week 2	(16) 18.40±4.70	(16) 21.80±7.60	0.142
Week 4	(16) 20.60±7.80	(16) 24.40±12.60	0.192
Week 8 dose escalation	(16) 19.20±4.30	(13) 23.20±9.80	0.235
Week 12	(15) 17.80±3.90	(9) 22.70±7.70	0.050*
Week 16 end of study	(15) 18.90±5.60	(9) 25.20±8.10	0.034*
ALT (U/L)
Screening	(16) 19.50±9.90	(16) 33.10±31.90	–
Baseline	(16) 18.00±7.60	(16) 27.30±18.80	0.131
Week 2	(16) 17.00±6.10	(16) 26.10±17.70	0.126
Week 4	(16) 18.30±13.20	(16) 27.10±21.70	0.052
Week 8 dose escalation	(16) 16.50±7.30	(13) 28.40±17.90	0.014*
Week 12	(15) 16.10±5.80	(9) 29.30±17.10	0.017*
Week 16 end of study	(15) 17.70±11.50	(9) 35.30±22.10	0.012*
Creatinine kinase (U/L)
Baseline	(16) 84.00±43.00	(16) 97.00±50.00	0.346
Week 16 end of study	(16) 92.00±45.00	(14) 86.00±42.00	0.787
Homocysteine
Baseline	(16) 10.75±2.32	(16) 10.31±2.77	0.632
Week 4	(16) 10.56±2.25	(16) 10.75±2.59	0.829
Week 8 dose escalation	(16) 11.25±2.27	(13) 9.85±2.30	0.111
Week 12	(15) 10.67±1.95	(9) 8.56±3.81	0.085
Week 16 end of study	(15) 10.20±1.66	(9) 9.78±2.05	0.585
hs-CRP
Baseline	(16) 1.65±1.61	(16) 3.51±3.44	0.038*
Week 4	(16) 1.69±1.58	(16) 3.47±3.33	0.040*
Week 8 dose escalation	(16) 1.87±1.72	(13) 3.42±3.60	0.227
Week 12	(15) 1.47±1.61	(9) 3.24±2.86	0.073
Week 16 end of study	(15) 1.48±1.59	(9) 3.27±2.64	0.042*
CoQ10
Baseline	(16) 0.89±0.17	(16) 0.93±0.21	0.895
Week 4	(16) 0.98±0.23	(16) 1.03±0.28	0.821
Week 8 dose escalation	(16) 1.08±0.27	(13) 1.13±0.37	0.948
Week 12	(15) 1.11±0.29	(9) 1.28±0.45	0.551
Week 16 end of study	(15) 1.15±0.32	(9) 1.32±0.45	0.531

Notes: Probability values P<0.05 are significant.

* P-values that were significantly different between groups. The between group statistical significance in red blood cells, MPV and AST values remained within the normal laboratory reference range.

Abbreviations: ALT, alanine transaminase; AST, aspartase aminotransferase; CoQ10, Coenzyme Q10; eGFR, estimated glomerular filtration rate; hs-CRP, high sensitivity C-reactive protein; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; MPV, mean platelet volume; RDW, red cell distribution width; SD, standard deviation.