Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence

Table 5

Omega-3 PUFA antineoplastic effect in subjects at high risk for CRC or in CRC patients: completed interventional human studies.

(a)

Type of study	Enrolled subjects	Number of subjects	Omega-3 PUFA daily treatments	Control group daily treatment	Length of treatments	Antineoplastic effect observed in omega-3 PUFA-treated subjects	Reference
Randomized double-blind, placebo-controlled trial	High risk for CRC (sporadic adenomatous polyps)	10 (control group); 10 (omega-3 PUFA group)	OS: 4.1 g EPA-EE + 3.6 g DHA-EE	OS: 7 g olive oil	2 wk.–3 mo.	Inhibition of abnormal rectal mucosa cell proliferation	[83]
Double-blind crossover trial	Healthy volunteers	12 (control group); 12 (omega-3 PUFA group)	OS: 11 g FO (providing 4.4 g omega-3 PUFA); omega-3/omega-6 ratio in the basal diet: 0.40	11 g; corn oil	2–4 wk.	Inhibition of rectal mucosa cell proliferation; inhibition of PGE2 release by rectal biopsies	[84]
Randomized double-blind, placebo-controlled trial	High risk for CRC (sporadic adenomatous polyps)	10 (control group); 10 (omega-3 PUFA group)	OS: 2.5 g; EPA-EE + DHA-EE	2.5 g; olive oil	1–6 mo.	Inhibition of abnormal rectal mucosa cell proliferation (in subjects with abnormal baseline proliferation pattern)	[85]
Double-blind crossover trial	Healthy volunteers	12 (control group); 12 (omega-3 PUFA group)	OS: 11 g FO (providing 4.4 g omega-3 PUFA); omega-3/omega-6 ratio in the basal high-fat diet: 0.25	11 g; corn oil	2–4 wk.	No effect on inhibition of rectal mucosa cell proliferation	[86]
Randomized double-blind, placebo-controlled trial	Patients with resected CRC or severely dysplastic polyps	10 (control group); 17 (omega-3 PUFA group)	OS: 9 g omega-3 PUFA-EE concentrate (providing about 4.0 g EPA-EE and 2.2 g DHA-EE)	9 g omega-6 PUFA-EE concentrate (providing about 4.5 g LA-EE)	6 mo.	Inverse association between colon omega-3/omega-6 PUFA and cell proliferation (in subjects with abnormal baseline proliferation pattern); suppression of polyp development	[87]

CRC: colorectal cancer; EE: ethyl ester; FAP: familial adenomatous polyposis; FFA: free fatty acid; FO: fish oil; LA: linoleic acid; OS: oral supplementation; TG: triglycerides.
The same subjects were treated with FO or CO in different periods.

(b)

Type of study	Enrolled subjects	Number of subjects	Omega-3 PUFA daily OS treatments	Control group daily OS treatment	Length of treatments	Antineoplastic effect observed in omega-3 PUFA-treated subjects	Reference
Randomized double-blind, placebo-controlled trial	Patients undergoing surgery for CRC	24 (control group); 25 (omega-3 PUFA group)	2 g FO; (providing 1.4 EPA + 1.0 DHA g n-3 PUFA)	2 g; safflower oil	12 days prior to surgery	No effect on frequency and spatial distribution of crypt cell mitosis	[88]
Single-blind (investigators) trial	Patients polypectomized for CR adenomas/tumors	20 (control group); 21 (omega-3 PUFA group)	FO; (providing 0.1 g EPA + 0.4 g DHA) and DA	No treatment; DA: reduction of fat consumption	2 years	Increased apoptosis in normal sigmoid colon mucosa	[89]
Randomized single-blind (investigators) trial	Patients with one or more CR adenomas	15 (control group); 15 (omega-3 PUFA group)	2 g; enteric coated EPA-FFA formulation	No treatment; DA: no fish intake	3 mo.	Reduced cell proliferation and increased apoptosis in normal colon mucosa crypts	[90]
Phase III randomised, double-blind, placebo-controlled trial	FAP patients	27 (control group); 28 (omega-3 PUFA group)	2 g; enteric coated EPA-FFA formulation	2 g; capric and caprylic acid medium-chain TG	6 mo.	Reduced polyp number and diameter	[91]
Phase II double-blind, randomised, placebo-controlled trial	Patients carrying CRC liver metastases	35 (control group); 36 (omega-3 PUFA group)	2 g; enteric coated EPA-FFA formulation	2 g; capric and caprylic acid medium-chain TG	12–65 days (median 30 days) prior to surgery	Reduced vascularity of CRC liver metastases	[92]

CRC: colorectal cancer; DA: dietary advice; FAP: familial adenomatous polyposis; FFA: free fatty acid; FO: fish oil; OS: oral supplementation; TG: triglycerides.
DA: reduction of fat intake and increase in omega-3 PUFA/omega-6 PUFA dietary ratio.