Effects of Phyllanthus amarus PHYLLPRO^TM leaves on hangover symptoms: a randomized, double-blind, placebo-controlled crossover study

Figures & data

Figure 1. Study flow chart. Fifteen of the 16 subjects screened were randomized in the study with 15 in the PHYLLPRO™ and placebo group, crossed over and included as the per-protocol final analysis. Subjects who received PHYLLPRO™ during Arm 1 received placebo during Arm 2. Subjects who received placebo during Arm 1 received PHYLLPRO™ during Arm 2.

Table 1. Baseline characteristics of subjects.

Baseline characteristics
N	15
Male number (percentage)	10 (66.67%)
Female number (percentage)	5 (33.33%)
Age in years (mean)	25 ± 8.9
Age in years (range)	21–47
Weight in lbs. (mean)	155.6 ± 15.1
Weight in lbs. (range)	134–193
BMI (mean)	23.9 ± 2.1
BMI (range) kg/m^2	20.4–28.3

Table 2. Effect of treatment on blood alcohol level (mean ± SD).

	Baseline	0.5 h	1 h	1.5 h	12 h	18 h	22 h
Active	0.000 ± 0.000	0.110 ± 0.021	0.130 ± 0.022	0.130 ± 0.014	0.000 ± 0.018^a	0.000 ± 0.000	0.000 ± 0.000
Placebo	0.000 ± 0.000	0.101 ± 0.032	0.120 ± 0.025	0.140 ± 0.016	0.050 ± 0.120	0.000 ± 0.000	0.000 ± 0.000

^aDenotes significant difference between groups p < 0.0001.

Table 3. Inflammatory cytokine panel and liver function of subjects at baseline to 22 h.

	Baseline		Hour 2		Hour 12		Hour 22
	treatment	Placebo	treatment	Placebo	treatment	Placebo	treatment	Placebo
CRP	0.89 ± 0.97	0.72 ± 0.88	0.90 ± 0.92	0.72 ± 0.82	0.83 ± 0.72	0.68 ± 0.79	0.86 ± 0.87	0.73 ± 0.85
Inflammatory cytokine panel
TNF-α	4.74 ± 1.10	5.07 ± 1.39	4.74 ± 1.03	5.00 ± 1.25	4.25 ± 1.14	4.52 ± 0.74	5.16 ± 1.68	5.30 ± 1.16
IL-1β	8.27 ± 3.73	7.81 ± 1.88	7.32 ± 1.79	7.82 ± 1.84	7.48 ± 1.79	7.60 ± 2.09	8.47 ± 1.92	8.40 ± 2.73
IL-2	4.17 ± 0.65	4.48 ± 0.83	4.15 ± 0.51	4.23 ± 0.84	4.01 ± 0.65	3.96 ± 0.64	4.43 ± 0.91	4.71 ± 1.14
IL-4	5.39 ± 1.60	5.09 ± 1.10	5.08 ± 1.56	5.27 ± 1.44	4.76 ± 1.57	4.79 + 0.63	5.92 ± 2.26	5.21 ± 1.07
IL-5	4.36 ± 1.55	4.16 ± 0.98	405 ± 1.07	4.67 ± 1.05	3.90 ± 1.00	4.45 ± 1.79	4.15 ± 0.94	4.70 ± 1.75
IL-6	2.94 ± 0.26	3.02 ± 0.05	3.02 ± 0.05	3.02 ± 0.05	3.00 ± 0.38	2.97 ± 0.13	3.27 ± 0.46	3.06 ± 0.14
IL-8	4.83 ± 0.79	5.24 ± 1.07	4.68 ± 0.73	4.77 ± 0.78	8.72 ± 4.84	5.69 ± 1.40	5.28 ± 0.68	4.19 ± 0.81#
IL-10	3.82 ± 0.61	4.35 ± 0.76	4.15 ± 0.62	4.04 ± 0.56	3.92 ± 0.40	4.10 ± 0.71	4.09 ± 0.45	4.23 ± 0.71#
IL-12p70	3.98 ± 0.80	4.99 ± 1.49	4.30 ± 0.70	4.48 ± 0.65	4.02 ± 0.54	4.41 ± 0.96	4.54 ± 0.84	4.62 ± 0.64#
IL-13	4.88 ± 0.94	4.84 ± 0.88	4.90 ± 0.96	5.21 ± 1.03	4.70 ± 0.74	4.61 ± 0.82	4.84 ± 0.84	5.11 ± 0.99
IL-17A	3.61 ± 0.47	3.87 ± 0.74	3.63 ± 0.48	3.73 ± 0.46	4.00 ± 0.53	3.68 ± 0.45	3.53 ± 0.52	3.67 ± 0.49
GM-CSF factor	5.87 ± 0.99	5.84 ± 0.53	5.55 ± 0.48	6.24 ± 0.78	5.51 ± 0.63	5.85 ± 0.80	6.27 ± 1.16	6.23 ± 1.01
Eotaxin	54.10 ± 39.89	68.67 ± 44.12	61.07 ± 50.93	55.02 ± 30.01	90.33 ± 61.2	92.93 ± 62.66	98.57 ± 67.84	87 ± 61.56
MIP-1beta	422.67 ± 161.14	410.72 ± 171.99	411.07 ± 195.48	381.52 ± 176.67	556.52 ± 183.08	586.23 ± 222.62	462.71 ± 145.04	485.18 ± 197.25
IFN-γ	5.67 ± 1.77	6.40 ± 2.10	5.66 ± 1.63	5.49 ± 1.26	5.54 ± 2.04	6.03 ± 2.62	5.78 ± 1.91	6.18 ± 2.32
VEGF	47.86 ± 24.02	61.67 ± 40.74	45.65 ± 24.23	51.33 ± 30.81	57.64 ± 37.68	64.72 ± 44.88	54.89 ± 29.34	62.12 ± 37.67
MCP-1	16.43 ± 6.31	15.54 ± 4.66	14.35 ± 5.09	15.15 ± 4.66	18.28 ± 5.21	20.64 ± 8.28	16.8 ± 4.67	17.55 ± 5.80
FGF-basic	4.31 ± 0.46	4.46 ± 0.51	4.30 ± 0.59	4.50 ± 0.56	4.55 ± 0.89	4.32 ± 0.46	4.70 ± 0.45	4.51 ± 0.50
Liver function tests
AST	21.8 ± 8.61	18.13 ± 5.30	21.6 ± 8.26	18.87 ± 5.14	18.79 ± 6.58	17.07 ± 3.9	17.08 ± 4.91	17.27 ± 3.84
ALT	18.13 ± 8.79	16 ± 5.68	18.33 ± 8.74	16.13 ± 5.65	16.21 ± 8.38	15.4 ± 5.15	15.92 ± 8.25	15.53 ± 5.64
Total bilirubin	0.51 ± 0.2	0.49 ± 0.22	0.48 ± 0.15	0.47 ± 0.17	0.42 ± 0.15	0.39 ± 0.12	0.59 ± 0.21	0.54 ± 0.22
Albumin	4.53 ± 0.29	4.41 ± 0.32	4.59 ± 0.35	4.45 ± 0.34	4.36 ± 0.35	4.36 ± 0.43	4.41 ± 0.31	4.45 ± 0.41
INR	1.04 ± 0.07	1.03 ± 006	1.03 ± 0.07	1.04 ± 0.06	1.06 ± 0.11	1.07 ± 0.09	1.06 ± 0.08	62.47 ± 14.88
ALK	63.88 ± 13.08	67.44 ± 14.17	66.31 ± 14.62	69.84 ± 13.31	62.84 ± 14.76	67.41 ± 15.23	62.47 ± 14.88	67.88 ± 15.61
GSH-Px	69.89 ± 15.77	74.69 ± 16.18	70.46 ± 15.52	71.48 ± 14.27	70.79 ± 9.60	75.3 ± 13.26	73.79 ± 11.66	76.86 ± 12.88

^#p < 0.05, Denotes significant difference of active compared to placebo.

Figure 2. Domains of (A) headache, (B) tremulousness, (C) dizziness and (D) diarrhoea within the Hangover Severity Score in the placebo and active groups within 22 h of the initiation of alcohol.

Table 4. Effect of treatment on Hangover Severity Score (mean ± SD).

	Baseline		Hour 2		Hour 10		Hour 12		Hour 18		Hour 22
	Active	Placebo	Active	Placebo	Active	Placebo	Active	Placebo	Active	Placebo	Active	Placebo
Nausea	0.00 ± 0.00	0.00 ± 0.00	0.20 ± 0.78	0.07 ± 0.26	0.00 ± 0.00	0.20 ± 0.41**	0.00 ± 0.00	0.07 ± 0.26*	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Headache	0.07 ± 0.26	0.07 ± 0.26	0.07 ± 0.26	0.00 ± 0.00*	0.00 ± 0.00	0.47 ± 1.06**	0.00 ± 0.00	0.27 ± 0.79**	0.00 ± 0.00	0.20 ± 0.78*	0.07 ± 0.26	0.07 ± 0.27
Anorexia	0.00 ± 0.00	0.00 ± 0.00	0.20 ± 0.56	0.00 ± 0.00**	0.00 ± 0.00	0.20 ± 0.56**	0.13 ± 0.52	0.20 ± 0.56	0.07 ± 0.26	0.33 ± 1.29	0.00 ± 0.00	0.00 ± 0.00
Dry mouth	0.13 ± 0.35	0.00 ± 0.00	0.13 ± 0.35	0.20 ± 0.56	0.31 ± 0.75	0.40 ± 0.91	0.20 ± 0.56	0.27 ± 0.59	0.13 ± 0.35	0.07 ± 0.26	0.13 ± 0.35	0.07 ± 0.27
Soreness	0.00 ± 0.00	0.07 ± 0.26*	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00^a	0.13 ± 0.35	0.07 ± 0.26	0.07 ± 0.26	0.00 ± 0.00	0.07 ± 0.26*	0.13 ± 0.52	0.07 ± 0.27*
Weakness	0.00 ± 0.00	0.07 ± 0.26*	0.00 ± 0.00	0.13 ± 0.52*	0.08 ± 0.28	0.13 ± 0.35	0.07 ± 0.26	0.07 ± 0.26	0.00 ± 0.00	0.07 ± 0.26*	0.00 ± 0.00	0.00 ± 0.00
Tremulousness	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.13 ± 0.35*	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Diarrhoea	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.07 ± 0.26	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Dizziness	0.00 ± 0.00	0.00 ± 0.00	0.13 ± 0.35	0.73 ± 1.79*	0.00 ± 0.00	0.33 ± 0.49***	0.00 ± 0.00	0.07 ± 0.26*	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Overall (how do you feel right now?)	1.20 ± 1.37	1.40 ± 1.24	1.50 ± 1.45	1.20 ± 1.47	1.77 ± 1.74	2.00 ± 1.73	1.47 ± 1.35	1.67 ± 1.54	1.27 ± 1.10	1.33 ± 1.29	1.20 ± 1.21	1.07 ± 1.28
If you needed to attend work or school right now, would you be able to?	0.00 ± 0.00	0.00 ± 0.00	0.20 ± 0.41	0.20 ± 0.41	0.23 ± 0.44	0.27 ± 0.46	0.20 ± 0.41	0.07 ± 0.26*	0.00 ± 0.00	0.00 ± 0.00	0.07 ± 0.26	0.00 ± 0.00*

*Denotes significant difference p < 0.05, ** p < 0.005, *** p < 0.0001, compared to baseline.

^a Denotes significant difference p < 0.05 between groups.

Table 5. The effect of treatment of Profile of Mood Scores.

	Before supplementation						After supplementation
	Baseline		Hour 2		Hour 10		Hour 12		Hour 18		Hour 22
	Active	Placebo	Active	Placebo	Active	Placebo	Active	Placebo	Active	Placebo	Active	Placebo
POMS
Tension-Anxiety	0.33 ± 0.72	0.40 ± 1.06	0.07 ± 0.26	0.13 ± 0.52	0.27 ± 1.03	0.33 ± 1.05	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.07 ± 0.26*	0.13 ± 0.52	0.67 ± 1.50*
Depression-Dejection	0.00 ± 0.00	0.00 ± 0.00	0.07 ± 0.26	0.13 ± 0.52	0.33 ± 0.82	0.00 ± 0.00*	0.07 ± 0.26	0.00 ± 0.00*	0.00 ± 0.00	0.00 ± 0.00	0.07 ± 0.26	0.00 ± 0.00*
Anger-Hostility	0.13 ± 0.52	0.020 ± 0.41	0.00 ± 0.00	0.13 ± 0.52*	0.87 ± 1.68	0.53 ± 1.36	0.13 ± 0.35	0.91 ± 0.24*	0.27 ± 0.59	0.00 ± 0.00*	0.33 ± 1.05	0.40 ± 0.91
Vigour-Activity	8.87 ± 6.65	10.40 ± 5.18	7.40 ± 5.59	9.93 ± 5.51	4.13 ± 5.14	3.80 ± 4.91	6.00 ± 6.21	6.60 ± 6.42	7.67 ± 7.08	8.47 ± 6.75	8.80 ± 7.51	9.80 ± 7.37
Fatigue-Inertia	0.73 ± 1.16	0.93 ± 1.22	0.47 ± 0.92	1.13 ± 1.81*	1.53 ± 2.07	2.20 ± 2.34	1.73 ± 2.63	1.67 ± 2.06	0.33 ± 0.72	0.60 ± 1.18	0.93 ± 2.15	0.47 ± 1.34
Confusion-Bewilderment	2.13 ± 1.99	1.60 ± 1.84	2.27 ± 1.75	2.13 ± 1.85	2.40 ± 1.72	2.67 ± 1.79	2.53 ± 1.68	2.53 ± 1.77	2.40 ± 1.99	2.13 ± 1.81	2.20 ± 1.94	1.93 ± 1.83
Overall Mood	−5.53 ± 9.97	−7.27 ± 8.10	−4.53 ± 7.32	−5.67 ± 8.25	1.27 ± 7.87	1.93 ± 8.49	−1.53 ± 8.61	−2.00 ± 9.72	−4.67 ± 9.15	−5.67 ± 9.12	−5.13 ± 11.35	−6.33 ± 10.66

*Denotes significant difference at p < 0.05, compared to baseline.