Effect of soy protein supplementation in patients with chronic hepatitis C: A randomized clinical trial

Table 1 Nutritional content per 100 g of supplement

	Whole soy powder1	Calcium caseinate
Energy (Kcal)	392	371
Carbohydrate (g)	14	0.2
Protein (g)	40	97.4
Total fat (g)	18.8	2.4
Alpha linolenic acid (mg)	1252	0
Linoleic acid (mg)	9332	0
Dietary fiber (g)	18	0
Isoflavones (mg)	53.82	0

¹Soyos^® ingredients.

Table 2 Characterization of the study population n (%)

	CG-casein	IG-soy	Total	P value
Demographic characteristics
Gender
Male	49 (61.2)	53 (66.2)	102 (63.8)	0.621
Female	31 (38.8)	27 (33.8)	58 (36.2)
Marital Status
Married	56 (70.0)	55 (68.7)	111 (69.4)	1.001
Single, widowed or divorced	24 (30.0)	25 (31.3)	49 (30.6)
Anthropometric data
Body mass index
< 25 kg/m2	40 (50.0)	43(53.8)	83 (51.9)	0.7511
≥ 25 kg/m2	40 (50.0)	37(46.2)	77 (48.1)
Waist circumference
Adequate	43 (53.7)	46 (59.0)	89 (56.3)	0.5251
Inadequate	37 (46.3)	32 (41.0)	69 (43.7)
Clinical data
Genotype
1	66 (88.0)	61 (79.2)	127 (83.5)	0.1891
2/3	9 (12.0)	16 (20.8)	25 (16.5)
Necroinflammatory activity
A0	26 (41.3)	29 (46.8)	55 (44.0)	0.7921
A1	26 (41.3)	22 (35.5)	48 (38.4)
A2 e A3	11 (17.4)	11 (17.7)	22 (17.6)
Stage of fibrosis
F0/F1/F2	35 (55.6)	40 (63.5)	75 (59.5)	0.4681
F3/F4	28 (44.4)	23 (36.5)	51 (40.5)
Hepatic steatosis
Yes	24 (40.0)	19 (29.7)	43 (34.7)	0.2601
No	36 (60.0)	45 (70.3)	81 (65.3)
HOMA-IR
< 3.0	55 (53.9)	47 (46.1)	102 (63.7)	0.251
≥ 3.0	25 (43.1)	33 (56.9)	58 (36.3)
Biochemical data	Median (iq r)	Median (iq r)
Glucose (mg/dL)	91.0 (14.2)	91.5 (14.2)		0.702
HOMA-IR	2.35 (2.24)	2.26 (2.59)		0.992
Triglycerides (mg/dL)	96.5 (60.2)	96.0 (67.2)		0.572
Total cholesterol (mg/dL)	149.0 (49.7)	160.0 (44.0)		0.422
HDL (mg/dL)	44.0 (14.2)	44.0 (15.5)		0.302
LDL (mg/dL)	90.5 (40.7)	90.0 (43.0)		0.942
AST (U/L)	59.5 (40.7)	52.0 (44.5)		0.142
ALT (U/L)	76.5 (54.5)	73.5 (53.0)		0.382
γGT (U/L)	102.0 (118.0)	87.0 (114.0)		0.712
Alkaline phosphatase (U/L)	79.0 (33.5)	80.0 (53.2)		0.492

¹Fisher’s exact test;

²Mann-Whitney; iq r: Interquartile range. n = 160. CG-casein: Control group-casein; IG-soy: Intervention group-soy; Adequate waist circumference: ≤ 80 cm for women and ≤ 94 cm for men. HOMA-IR: Homeostasis model assessment index of insulin resistance; HDL: High density lipoprotein; LDL: Low density lipoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γGT: Gamma glutamyl transferase.

Table 3 Comparison of the distribution of hepatic steatosis before and after intervention between groups of patients with hepatitis C virus

Hepatic Steatosis	n	Yes	No	P value
Before				0.26041
IG-soy	64	19 (29.7)	45 (70.3)
CG-casein	60	24 (40.0)	36 (60.0)
After				0.18501
IG-soy	64	10 (15.6)	54 (84.4)
CG-casein	60	16 (26.7)	44 (73.3)
IG-soy: before vs after				0.0076 2
With hepatic steatosis	19	10 (52.6)	9 (47.4)
Without hepatic steatosis	45	0 (0.0)	45 (100.0)
GC-casein: before vs after				0.01332
With hepatic steatosis	24	16 (66.7)	8 (33.3)
Without hepatic steatosis	36	0 (0.0)	36 (100.0)

¹Fisher's exact test: Comparison between groups before and after intervention;

²Paired analysis: McNemar’s test: Comparison in each group. CG-casein: Control group-casein; IG-soy: Intervention group-soy.

Table 4 Median values of biochemical tests in patients with hepatitis C virus after protein supplementation

	CG-casein		IG-soy		Treatment difference
Exams	n	median (iq r)	n	median (iq r)	P value1
Total cholesterol (mg/dL)	80	152.0 (61.5)	80	153.0 (44.7)	0.54
HDL (mg/dL)	80	46.0 (17.0)	80	43.5 (15.2)	0.21
LDL (mg/dL)	80	89.5 (45.0)	80	84.5 (41.5)	0.39
AST (U/L)	78	61.5 (40.5)	80	49.5 (44.2)	0.02
ALT (U/L)	78	73.0 (65.7)	79	64.0 (50.0)	0.007
γGT (U/L)	75	108.0 (120.5)	73	84.0 (107.0)	0.09
HOMA-IR	79	2.4 (2.7)	80	2.6 (2.2)	0.91

¹Mann-Whitney test (P < 0.05): comparison between groups; Bonferroni correction (P < 0.007); CG-casein: Control group-casein; IG-soy: Intervention group-soy; iq r: Interquartile range; n < 80: When an examination was not performed; HOMA-IR: Homeostasis model assessment index of insulin resistance; HDL: High density lipoprotein; LDL: Low density lipoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γGT: Gamma glutamyl transferase.

Table 5 Median values of biochemical tests in patients with hepatitis C virus at the beginning of monitoring and after protein supplementation

	IG-soy						CG-casein
		Baseline	12 wk					Baseline	12 wk
Exams	n	Median (iq r)	Median (iq r)	change	% change	P value1	n	Median (iq r)	Median (iq r)	change	% change	P value1
Total cholesterol (mg/dL)	80	160.0 (44.0)	153.0 (44.7)	-7.0	-7.37	0.05	80	149.0 (49.7)	152.0 (61.5)	+3.0	+2.01	0.63
HDL (mg/dL)	79	44.0 (15.5)	43.5 (15.2)	-0.5	-1.14	0.69	80	44.0 (14.2)	46.0 (17.0)	+2.0	+5.54	0.13
LDL (mg/dL)	78	90.0 (43.0)	84.5 (41.5)	-5.5	-6.11	0.03	80	90.5 (40.7)	89.5 (45.0)	-1.0	-1.10	0.66
AST (U/L)	80	52.0 (44.5)	49.5 (44.2)	-2.5	4.81	0.32	78	59.5 (40.7)	61.5 (40.5)	+2.0	+3.36	0.04
ALT (U/L)	76	73.5 (53.0)	64.0 (50.0)	-9.5	-12.92	0.006	78	76.5 (54.5)	73.0 (65.7)	-3.5	-4.57	0.48
γGT (U/L)	73	87.0 (114.0)	84.0 (107.0)	-3.0	-3.45	0.007	75	102.0 (118.0)	108.0 (120.5)	+6.0	+5.88	0.19
HOMA-IR	80	2.3 (2.6)	2.6 (2.2)	+0.3	+13.04	0.23	79	2.3 (2.2)	2.4 (2.7)	+0.1	+4.35	0.09

¹Paired analysis: Wilcoxon test (P < 0.05): Change in the group, the Bonferroni correction (P < 0.007). HDL: High density lipoprotein; LDL: Low density lipoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γGT: Gamma glutamyl transferase; CG-casein: Control group-casein; HOMA-IR: Homeostasis model assessment index of insulin resistance; IG-soy: Intervention group-soy; iq r: Interquartile range; n < 80: When an examination was not performed.

Table 6 Logistic regression model for factors predictive of hepatic steatosis in patients with hepatitis C virus after 12 wk of protein supplementation

	Bivariate analysis		Multivariate analysis
	Crude OR (95% IC)	P value	Adjusted OR1 (95% IC)	P value
Groups
Control-casein	1		1
IG-soy	0.51 (0.20-1.22)	0.135	0.25 (0.06-0.82)	0.032
HOMA-IR
< 3.0	1		1
≥ 3.0	1.97 (0.82-4.77)	0.129	3.49 (1.10-11.90)	0.037
Stage of fibrosis
F0/F1/F2	1		1
F3/F4	1.78 (0.68-4.69)	0.239	1.59 (0.50-5.40)	0.436
γGT
< 85 U/L	1		1
≥ 85 U/L	2.07 (0.81-5.64)	0.135	1.52 (0.47-5.18)	0.487
HDL-C
≥ 35 mg/dL	1		1
< 35 mg/dL	1.25 (0.41-3.40)	0.677	2.18 (0.56-8.21)	0.247

¹Adjusted for the other variables shown in the table; γGT: 85 U/L upper limit of normal. γGT: Gamma glutamyl transferase; HOMA-IR: Homeostasis model assessment index of insulin resistance; HDL: High density lipoprotein; IG-soy: Intervention-soy; OR: Odd ratio; 95% IC: 95% confidence interval.

Table 7 Logistic regression model for factors predictive of homeostasis model assessment of insulin resistance in patients with hepatitis C virus after 12 wk of protein supplementation

	Bivariate analysis		Multivariate analysis
	Crude OR (95% IC)	P value	Adjusted OR1 (95% IC)	P value
Groups
Control-casein	1		1
Intervention-soy	0.90 (0.47-1.70)	0.745	1.92 (0.80-4.83)	0.15
Stage of fibrosis
F0/F1/F2	1		1
F3/F4	4.21 (1.99-9.19)	0.0002	5.25 (2.17-13.67)	0.0004
Alanine aminotransferase
1.5 times below ULN	1		1
1.5 times above ULN	2.22 (1.16-4.30)	0.017	3.26 (1.30-8.71)	0.014
Marital status
Married	1		1
Single, widowed or divorced	0.52 (0.24-1.07)	0.081	0.24 (0.08-0.65)	0.007
Waist circumference2
Adequate	1		1
Inadequate	2.62 (1.37-5.16)	0.004	5.57 (2.23-15.27)	0.0004

¹Adjusted for the other variables shown in the table;

²Adequate waist circumference: ≤ 80 cm for women and ≤ 94 cm for men; ULN: Upper limit of normal; OR: Odd ratio; 95% IC: 95% confidence interval.

Table 8 Logistic regression model for factors predictive of alanine aminotransferase levels in patients with hepatitis C virus after 12 wk of protein supplementation

	Bivariate analysis		Multivariate analysis
	Crude OR (95% IC)	P value	Adjusted OR1 (95% IC)	P value
Groups
Control-casein	1		1
IG-soy	0.55 (0.29-1.04)	0.068	0.45 (0.22-0.89)	0.024
HOMA-IR
< 3.0	1		1
≥ 3.0	2.22 (1.16-4.30)	0.017	3.16 (1.51-6.93)	0.001
Gender
Male	1		1
Female	0.39 (0.20-0.77)	0.007	0.28 (0.12-0.60)	0.003
HDL-C
≥ 35 mg/dL	1		1
< 35 mg/dL	3.15 (1.37-7.76)	0.008	2.85 (1.18-7.40)	0.024

¹Adjusted for the other variables shown in the table. HOMA-IR: Homeostasis model assessment index of insulin resistance; HDL: High density lipoprotein; IG-soy: Intervention-soy; OR: Odd ratio; 95% IC: 95% confidence interval.