Effects of Polyunsaturated Fatty Acids on Colorectal Cancer Patients: A Meta-Analysis of Randomized Controlled Trials

Figures & data

Figure 1. Flow diagram of selection.

Table 1. Characteristics of included studies in the meta-analysis.

Author (Year)	Country	Experimental	Control	Treatment	Duration time	Intervention (dosage, frequency)	Mode of administration
Bakker et al. (2020)	Netherlands	18	23	Surgery	Perioperative	Fish oil (0.2 g/kg/d)	Intravenous
Braga et al. (2002)	Italy	50^a	50	Surgery	Preoperative	Arginine and n-3 fatty acids (1 L/d)	Oral
		50^b			Perioperative
Finco et al. (2007)	Italy	14	14	Surgery	Perioperative	Arginine, n-3 fatty acids and RNA (750 ml/d)	Oral
Haidari et al. (2020)	Iran	20^c	20^d	Chemotherapy	8 weeks	n-3 fatty acids (660 mg/d)	Oral
		20^e	21^f			n-3 fatty acids (660 mg/d)
Horie et al. (2006)	Japan	33	34	Surgery	Preoperative	Arginine, n-3 fatty acids and RNA (750 ml/d)	Oral
Liang et al. (2008)	China	21	21	Surgery	Postoperative	Fish oil (0.2 g/kg/d)	Intravenous
Mocellin et al. (2013)	Brazil	6	5	Shemotherapy	9 weeks	Fish oil (2 g/d)	Oral
Mohammadzadeh et al. (2013)	Iran	16	18	Chemotherapy	6 weeks	CLA (3 g/d)	Oral
Pastore-Silva et al. (2012)	Brazil	11	12	Chemotherapy	9 weeks	Fish oil (2 g/d)	Oral
Purasiri et al. (1994)	U.K.	14	6	Chemotherapy	2 mo,^g	γ-linolenic acid, DHA, EPA (2.384 g/d-4.768g/d)	Oral
Sorensen et al. (2014)	Denmark	74	74	Surgery	Perioperative	n-3 fatty acids (400 ml/d)	Oral
Zhu et al. (2012)	China	29	28	Surgery	Postoperative	Fish oil (0.2 g/kg/d)	Intravenous

NR: not reported; RNA: ribonucleic acid; CLA: conjugated linoleic acid; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid.

^a Oral intake for 5 day before surgery of a formula enriched with arginine and n-3 fatty acids (preoperative group; n = 50).

^b Same preoperative treatment prolonged after surgery by jejunal infusion (perioperative group; n = 50).

^c Omega-3 fatty acid arm, receiving two 330 mg omega-3 fatty acid capsules daily and placebo (for vitamin D3) weekly.

^d Controls, receiving placebos.

^e Co-supplementation arm, receiving a 50,000 IU vitamin D3 soft gel weekly and two 330 mg omega-3 fatty acids capsules daily for 8 weeks.

^f Vitamin D arm, receiving a 50,000 IU vitamin D3 soft gel weekly and two placebos (for omega-3 fatty acids) daily.

^g The original intervention was 6 mo, but compared with other included articles, the data for 2 mo, were more comparable.

Figure 2. Forest plot of the association between PUFAs supplementation and postoperative infectious complications in patients with CRC.

Table 2. Analysis of postoperative complications outcomes.

Experimental vs. Control	No. of studies	RR/WMD	95%CI	p	Heterogeneity(I^2)
Infectious
Surgical site infection	6	0.90	0.51, 1.59	0.73	0%
Preoperative	2	0.37	0.05, 2.84	0.34	44%
Perioperative	4	1.11	0.58, 2.14	0.75	0%
Urinary tract infection	6	0.57	0.24, 1.35	0.20	1%
Preoperative	2	0.39	0.09, 1.61	0.19	0%
Perioperative	4	0.86	0.19, 3.86	0.84	43%
Pneumonia	3	1.32	0.63, 2.76	0.46	0%
Perioperative	2	1.43	0.67, 3.05	0.36	0%
Abscess	3	0.64	0.10, 4.14	0.64	34%
Perioperative	3	0.77	0.06, 9.72	0.84	53%
Anastamotic leak	5	0.87	0.38, 2.00	0.74	24%
Preoperative	2	0.47	0.14, 1.61	0.23	0%
Perioperative	3	1.20	0.36, 3.97	0.77	41%
Noninfectious
Noninfectious complications	2	1.35	0.86, 2.12	0.19	0%
Perioperative	2	1.35	0.84, 2.17	0.21	0%
Ileus	4	2.60	0.58, 11.65	0.21	0%
Preoperative	2	1.03	0.07, 15.80	0.98	Not applicable
Perioperative	3	3.88	0.64, 23.38	0.21	0%
Wound dehiscence	2	0.84	0.24, 2.95	0.79	0%
Perioperative	2	0.81	0.20, 3.29	0.76	0%
Deep venous thrombosis	2	0.69	0.11, 4.34	0.69	0%
Perioperative	2	1.00	0.11, 9.45	1.00	0%
Length of hospital stay	6	−1.19^a	−2.62, 0.24	0.10	79%
Preoperative	2	−2.27^a	−3.58, −0.97	<0.001	0%
Perioperative	3	−0.08^a	−1.97, 1.80	0.93	84%
Postoperative	2	−2.66^a	−4.70, −0.62	0.01	0%
Death (Perioperative)	3	1.35	0.26, 7.02	0.72	0%

RR: risk ratio; WMD: weighted mean difference; CI: confidence interval.

^a Indicates continuous data, using MD.

Table 3. Analysis of immune regulation, inflammatory and nutritional status outcomes.

Experimental vs. Control	No. of studies	WMD/SMD	95%CI	p	Heterogeneity(I^2)
Inflammatory
IL-1β (Chemotherapy)	4	0.14^a	−0.19, 0.47	0.40	0%
CD4 (Surgery)	2	4.20	−1.57, 9.97	0.15	55%
CD8 (Surgery)	2	−3.49	−7.89, 0.91	0.12	47%
Ratio of CD4/CD8 (Surgery)	2	0.32	−0.03, 0.68	0.07	0%
Nutritional status
Weight (Chemotherapy)	3	0.97	−3.85, 5.79	0.69	19%
BMI (Chemotherapy)	3	0.26	−1.06, 1.58	0.70	0%

SMD: standard mean difference; WMD: weighted mean difference; CI: confidence interval; IL-1β: interluekin-1β; BMI: body mass index.

^a Using SMD.

Figure 3. Forest plot of the association between PUFAs supplementation and albumin in in patients with CRC.

Figure 4. Forest plot of the association between PUFAs supplementation and CRP in in patients with CRC.

Figure 5. Forest plot of the association between PUFAs supplementation and TNF-α in in patients with CRC.

Figure 6. Forest plot of the association between PUFAs supplementation and IL-6 in in patients with CRC.

Availability of Data and Materials

The datasets supporting this article’s conclusions are included within the article and its additional files.