Lifestyle-related disease in Crohn’s disease: Relapse prevention by a semi-vegetarian diet

Table 1 Details of patients’ data

Case No.	Sex	Age (yr)	Type of disease	Anal lesion		Disease duration	Previous segmental resection	Initial onset or relapse	Hospitalization
				Fistula	Tag				On admission		Main medication	Duration of SVD (d)	On discharge
									CDAI	CRP (mg/dL)			CDAI	CRP (mg/dL)	Morphology
1	F	52	C	-	-	< 1 mo	-	I	161	0.6	Sulfasalazine	58	25	0.9	Active (CS)
2	M	22	C	+	+	4 yr and 3 mo	+	R	264	3.1	Infliximab	55	62	0	NT
3	F	21	EC	+	-	5 yr and 8 mo	-	R	133	6.3	Infliximab	48	38	0	NT
4	M	22	EC	+	-	5 yr and 3 mo	-	R	679	5.9	Infliximab	82	72	0.1	Remission (CS)
5	M	23	EC	+	-	< 2 mo	-	I	235	1.5	Infliximab	55	98	0.1	Near remission (CS)
6	M	28	C	-	-	2 mo	-	I	88	2.5	Infliximab	68	59	0.5	Near remission (CS)
7	F	77	C	-	-	1 yr and 10 mo	-	R	233	13.8	Infliximab	49	39	0	Remission (CS and BE)
8	M	30	C	+	-	6 mo	-	I	281	4.6	Infliximab	50	39	0.1	Remission (CS)
9	M	55	C	+	+	8 mo	-	I	172	1.0	Infliximab	46	67	0.5	Remission (CS and BE)
10	M	19	EC	+	-	4 mo	-	I	147	0.8	Infliximab	43	40	0	Remission (CS and BE)
11	F	21	EC	-	+	3 mo	-	I	335	6.0	Infliximab	49	47	0.3	Improved still active (CS and BE)
12	F	50	E	-	-	1 mo	-	I	488	5.1	Infliximab	43	53	0	Remission (CS)
13	M	28	C	-	-	3 mo	-	I	52	0.6	Infliximab	50	2	0	Remission (CS)
14	M	19	EC	+	+	2 yr and 1 mo	-	I	193	0.8	Infliximab	43	35	0	Near remission (CS and BE)
15	M	29	C	+	-	1 yr and 4 mo	-	I	126	0.2	Infliximab	43	8	0	Improved still active (CS)
16	M	30	C	+	-	1 yr and 1 mo	-	I	211	11.8	Infliximab	47	28	0.8	Near remission (CS and BE)
17	F	21	EC	-	+	6 yr and 2 mo	-	R	544	3.7	Infliximab	46	64	0.3	Improved still active (BE)
18	F	45	EC	-	-	13 yr	+	R, PO 21st d	143	0.2	Metronidazole	19	105	0.1	NT
19	M	21	EC	+	+	2 yr	-	I, PO 13th d	217	1.1	Metronidazole	18	166	0.1	NT
20	M	34	EC	-	-	17 yr	-	R, PO 12th d	146	0	Metronidazole	24	108	0.1	NT
21	M	25	C	-	+	13 yr	-	R, PO 17th d	372	7.1	Metronidazole	21	149	0	NT
22	F	23	EC	-	-	8 yr	-	R, PO 25th d	151	8.0	Metronidazole	83	141	0.8	NT

F: Female; M: Male; EC: Enterocolitis; C: Colitis; E: Enteritis; R: Relapse; I: Initial onset; PO: Postoperative; CDAI: Crohn's disease activity index; CRP: C-reactive protein (normal range ≤ 0.3 mg/dL); SVD: Semi-vegetarian diet; CS: Colonoscopy; BE: Barium enema study; NT: Not tested.

Table 2 Nutritional data and hemoglobin during hospitalization

Case No.	Dietary pattern beforehospitalization	Hospitalization
		On admission					On discharge
		BMI (kg/m2)	Albmin(g/dL)	Chol(mg/dL)	ChE(IU/mL)	Hemoglobin(g/dL)	BMI (kg/m2)	Albmin(g/dL)	Chol(mg/dL)	ChE(IU/mL)	Hemoglobin(g/dL)
1	Pro-Japanese	21.1	4.7	155	4929	14.8	20.5	4.1	145	4959	13.0
2	Standard	17.2	3.8	140	4059	14.0	17.1	4.5	145	4170	15.5
3	Japanese	17.2	3.7	102	2003	8.3	19.2	4.0	152	4117	11.1
4	Pro-Japanese	18.5	2.8	100	789	8.6	17.9	3.0	116	1876	12.7
5	Pro-western	17.7	4.8	132	5592	15.8	17.0	4.2	135	5057	14.4
6	Pro-western	21.3	3.0	122	2876	10.8	20.7	4.4	192	4321	10.8
7	Pro-Japanese	17.2	2.1	95	1549	7.5	16.8	3.2	177	2633	11.6
8	Pro-western	19.2	3.2	128	3441	12.6	18.3	4.2	114	4911	14.3
9	Japanese	19.7	3.9	190	5094	13.0	18.2	4.1	221	4602	14.1
10	Pro-western	17.6	4.0	147	4505	13.5	17.6	4.5	154	4725	13.7
11	Standard	19.8	3.7	147	4081	9.5	18.4	3.9	125	4837	10.3
12	Standard	24.1	4.4	149	5156	11.0	21.4	4.3	158	6626	10.7
13	Standard	24.4	4.6	151	4599	16.2	22.5	4.4	143	4376	15.1
14	Pro-western	19.0	4.7	167	5722	15.0	18.8	4.4	138	4861	16.0
15	Pro-western	24.1	4.6	188	5755	15.4	22.4	4.5	137	5643	15.8
16	Pro-western	22.5	3.7	138	3757	12.3	21.4	4.4	116	4304	14.3
17	Standard	18.8	3.8	187	2700	10.6	18.1	4.1	209	2798	11.8
18	Pro-Japanese	21.6	4.1	126	7943	10.7	21.9	3.9	129	9098	10.8
19	Pro-western	20.1	4.1	150	3320	11.0	20.1	4.2	152	3426	11.8
20	Polymeric diet	18.1	3.9	100	3512	11.0	17.9	4.1	130	3757	13.4
21	Standard	15.6	3.5	116	3387	10.2	15.6	4.0	138	3870	11.9
22	Pro-Japanese	16.5	3.2	58	2320	9.9	16.0	2.9	78	3355	9.8

Standard: A mixture of Japanese and western diet; BMI: Body mass index; Chol: Total serum cholesterol; ChE: Cholinesterase. Normal range: BMI: 18.5 kg/m²≤-< 25.0 kg/m²; Albmin: 3.8-5.2 g/dL; Chol: 120-220 mg/dL; ChE: 3200-6500 IU/mL; Hemoglobin: M: 13.8-17.5 g/dL, F: 12.0-15.1 g/dL.

Table 3 Lifestyle and dietary habits

	Every day	3-5 times/wk	1-2 times/wk	Rare	None
Smoking (No. of cigarettes/d)	20 ≤	6-19	1-5	Rare	P
Regular exercise	R	R	R		P
Alcohol					P
Eating between meals			P	R	R
Type of diet (D)	Semi-vegetarian (R)	Japanese	Pro-Japanese	Standard/mixed	Pro-western (P)
Food
Rice	P
Miso soup	P
Pulses	R	P
Vegetables	R	P
Udon/soba (Japanese noodles)				P
Ramen (Chinese noodles)			P	R
Bread (D)	P			R
Tea, coffee		Canned coffee (P)		R
(Sugar in tea or coffee) (D)	Large amount (P)	Average amount	Small amount	Rare	None (R)
Juice	P			R	R
Cola/soda					P
Beef			P	R
Pork/chicken (D)		P		R
Minced or processed meat			P	R
Fish				P
Cheese/butter/margarine			P	R
Sweets (D)	P			R	R
Ice cream/milk shake				P
Yoghurt (plain)	R				P
Green tea (D)	R				P
Potatoes/starches (D)	R		P
Fruits (D)	R				P

P: Your present habit (style); R: Recommended habit (style); D: Drastic alteration recommended.

Table 4 Content of semi-vegetarian diet (2000 kcal/d)

	SVD	DRI
Energy
Protein (%)	16.1 ± 0.5	< 20
Fat (%)	18.6 ± 1.4	20-30
Carbohydrate (%)	66.1 ± 1.6	50-70
Content
Protein (g)	80.3 ± 3.0	M 60, F 50
Fat (g)	41.4 ± 3.6
Carbohydrate (g)	330.2 ± 11.4
Dietary fiber (g)	32.4 ± 2.1	M 20, F 17
Soluble dietary fiber (g)	6.8 ± 0.7
Insoluble dietary fiber (g)	23.3 ± 1.6
Calcium (mg)	873.7 ± 65.2	M 600-650, F 600
Phosphorus (mg)	1882.7 ± 101.8	M 1050, F 900
Iron (mg)	19.3 ± 1.3	M 7.5, F 10.5
Sodium (mg)	4492.9 ± 342.1	600
Kalium (mg)	4281.7 ± 250.6	M 2000, F 1600
Vitamin A (μgRE)	1416.6 ± 360.9	M 750, F 600
Vitamin B1 (mg)	2.0 ± 0.2	M 1.4, F 1.1
Vitamin B2 (mg)	1.3 ± 0.2	M 1.6, F 1.2
Niacin (mg)	26.6 ± 3.1	M 15, F 12
Vitamin C (mg)	133.1 ± 23.4	100
Vitamin D (μg)	3.2 ± 1.0	5
Vitamin E (mg)	12.3 ± 1.9	M 9, F 8
Cholesterol (mg)	285.9 ± 72.1	M < 700, F < 600
NaCl (g)	10.9 ± 0.8	M < 10, F < 8
Polyunsaturated fatty acid (g)	13.9 ± 1.9
Monounsaturated fatty acid (g)	9.3 ± 0.9
Saturated fatty acid (g)	7.1 ± 0.9
P:S ratio	2.0 ± 0.2

SVD: Semi-vegetarian diet, Figure is mean ± 1SD of 28 d; DRI: Dietary reference intakes for Japanese[52], Figures for ages above 18 are shown; P:S: Polyunsaturated fatty acids:saturated fatty acids.

Table 5 Follow-up study

Case No.	Main medication	Dietary pattern				Days of remission	Reason for termination	On final attendance
		Month 3	Year 1	Year 2	On relapse			CDAI	CRP (mg/dL)	BMI (kg/m2)	Alb (g/dL)	Chol (mg/dL)	ChE (IU/mL)	Hemoglobin (g/dL)
1	SSZ for 1 yr	SVD	SVD	SVD		730	Completion	0	0.1	23.1	4.5	235	5684	14.4
2	Mesalamine	SVD	Omni		Omni	301	Relapse	193	8.2	17.5	3.8	151	3262	13.8
3	Mesalamine	SVD	Omni		Omni	367	Relapse	167	11.3	21.1	3.5	133	3551	10.0
4	Mesalamine	SVD	SVD	SVD		730	Completion	128	5.0	18.7	2.8	114	1113	9.3
5	SSZ for 1 yr	SVD	SVD			523	Moving	39	0	19.4	4.5	194	5509	15.0
6	Mesalamine	Omni			Omni	191	Relapse	192	5.7	21.7	3.9	134	3052	7.9
7	None	SVD	SVD			442	INFX for RA	61	2.0	19.6	4.0	158	5068	10.9
8	Mesalamine	SVD	SVD		SVD	635	Relapse	174	7.6	19.1	3.1	88	2678	11.3
9	Mesalamine	Omni	Omni	Omni		730	Completion	48	0.2	19.8	4.3	171	5461	15.2
10	Mesalamine	SVD	SVD	SVD		730	Completion	18	0.1	18.2	5.1	181	4659	16.3
11	Mesalamine	SVD	SVD	SVD		730	Completion	11	0	19.7	4.7	147	5215	13.9
12	Mesalamine	SVD	SVD	SVD		730	Completion	45	0	20.2	4.7	163	6268	11.3
13	Mesalamine	SVD	SVD	SVD		730	Completion	0	0	22.8	4.6	171	4770	15.6
14	Mesalamine	SVD	SVD			666	Ongoing	27	0.1	19.3	4.7	188	6084	15.1
15	Mesalamine	SVD	Omni			560	Ongoing	0	0	22.6	4.8	185	5671	16.8
16	Mesalamine	SVD	SVD			440	Ongoing	19	1.9	21.8	4.4	141	5146	14.2
17	Mesalamine	SVD	SVD			397	Ongoing	32	2.0	22.5	3.6	216	2683	11.1
18	Mesalamine	SVD	SVD	SVD		730	Completion	25	0.4	22.6	3.7	151	10222	11.1
19	Mesalamine	SVD	SVD	SVD		730	Completion	62	0	20.1	4.7	139	4391	13.3
20	None	SVD	SVD	SVD		730	Completion	37	0.7	18.2	4.5	156	5655	13.2
21	SSZ	SVD	SVD	SVD		730	Completion	16	0.1	19.0	4.9	205	6424	14.4
22	Mesalamine	SVD	Omni		Omni	630	Relapse	118	5.1	22.1	3.5	84	3596	10.1

Alb: Albumin; SSZ: Sulfasalazine; Omni: Omnivorous diet; INFX: Infliximab; RA: Rheumatoid arthritis. Normal range: CRP: ≤ 0.3 mg/dL; BMI: 18.5 kg/m²≤-< 25.0 kg/m²; Albmin: 3.8-5.2 g/dL; Chol: 120-220 mg/dL; ChE: 3200-6500 IU/mL; Hemoglobin: M: 13.8-17.5 g/dL, F: 12.0-15.1 g/dL.

Table 6 Maintenance therapy in Crohn's disease following induction of remission or response

	Induction therapy		Maintenance therapy
	Subjects	Regimen	Regimen	Duration
				1 yr	2 yr
Candy et al[55], 1995	CDAI > 200	PS (diminishing dose) + AZA 12 wk	AZA 2.5 mg/kg	Remission rate 42% (14/33)
			Placebo	7% (2/30)
Hanauer et al[56], 2002	CDAI ≥ 220	Gr (1) and Gr (2)	Gr (1) INFX 5 mg/kg every 8 wk	Remission rate 25% (28/113)
	Responder to a single infusion of infliximab	INFX 5 mg/kg at weeks 0, 2, 6	Gr (2) INFX 10 mg/kg every 8 wk	33% (37/112)
		Gr (3) INFX 5 mg/kg then placebo infusion at weeks 2, 6	Gr (3) placebo infusion every 8 wk	11% (12/110)
Sandborn et al[58], 2005	Mild to moderate CD	Budesonide 6 mg or 3 mg	Budesonide 6 mg or 3 mg	Relapse rate 60%-70%
			Placebo	(In all 3 groups)
Takagi et al[39], 2006	Active CD	TPN (25 cases), TEN (22 cases),	ED (half) + a free diet (half)	Relapse rate 26.9% (7/26)
		PS (1 case), INFX (3 cases)	A free diet	64.0% (16/25)
Regueiro et al[59], 2009	CD patients who had surgery	Ileocolonic resection	INFX 5 mg/kg at weeks 0, 2, 6	Remission rate 80% (8/10)
			then every 8 wk
			Placebo	58% (7/13)
Present study	Active CD	INFX 5 mg/kg at weeks 0, 2, 6 (16 cases), intestinal resection (5 cases), SSZ (1 case)	Semi-vegetarian diet	Remission rate 100% (16/16)	92%
			Omnivorous diet	67% (4/6)	25%

PS: Prednisolone; AZA: Azathioprine; CD: Crohn's disease; TPN: Total parenteral hypernutrition; TEN: Total enteral nutrition; ED: Elemental diet.

Table 7 Conventional and current diet in IBD at Nakadori General Hospital

	Conventional	Current
Diet	Low-residue diet	Semi-lactoovovegetarian diet
Menu	Common for UC and CD	SVD for UC (staple: white rice)
		SVD for RUC (staple: white rice 70%, brown rice 30%)
		SVD for CD (staple: brown rice)
Refrainment	Fiber-rich diet	Minced or processed meat, bread, fast foods, sweets, cola/soda, juices
Dairy products	Refrainment	Egg, milk: no refrainment
		Refrain from cheese/butter/margarine
Calories	2000 kcal/d	About 30 kcal/kg standard body weight/d
Dietary analysis	Absent	Food-frequency questionnaire
Dietary guidance	Absent	Guidance by doctor and registered dietitian

UC: Ulcerative colitis; RUC: Refractory ulcerative colitis.