Table 3.
Randomized controlled trials providing oral N-3 supplementation.
| Cancer Type (Stage) | N (Int/CNT) Female/Male |
Age Body Weight and BMI (Int/CNT) |
Chemotherapy | N-3 (g EPA + DHA/Day) CNT |
Treatment Duration |
Experimental Findings | Ref |
|---|---|---|---|---|---|---|---|
| Lung, Head and Neck, Gynecologic, Breast, Prostate, Urinary Tract, Esophagus (I–IV) |
38 20/18 14 F/24 M |
Age = 62.7 ± 11.0 Body weight = 70.8 ± 12.6 BMI = 24.8 ± 3.5 |
Radiotherapy | 2 × 326 kcal: 2.4 g EPA + 1.2 g DHA + 40 g protein CNT = N/A |
7 days | N-3: ↓ serum PGE2 Control: ↑ serum PGE2 No differences in cytokine production |
2013 [15] |
| Stomach, Colon, Lung, Pancreas, Other | 40 | Age = 61.3 ± 12.1/63.6 ± 11.4 BMI = 20.9 ± 3.7/22.2 ± 3.8 |
Chemotherapy ± radiation or no treatment | 600 kcal: 1.5 g EPA + 19.5% protein CNT = isocaloric supplement |
1 month | Both groups: ↑ SF36 N-3: ↓ in IFNγ Control: ↑ in IFNγ |
2011 [21] |
| Head and Neck (I–IV) |
27 (13/14) 11 F/16 M |
Age = 61.5(45–77)/66.1 (47–76) BMI = NS but cachexic |
Surgery | 600 kcal: 2.1 g EPA + 32 g protein CNT = N/A |
4 weeks | No differences between groups or from baseline | 2018 [17] |
| Head and Neck (I–IV) |
64 29 F/35 M |
Age = 60 ± 14/58 ± 14 Body weight = 58.8 ± 1.4/61.1 ± 11.5 BMI = 22.6 ± 4.6/24 ± 4.2 weight loss = ~9 kg in 3 months before entry |
Surgery, radiotherapy, chemotherapy, or combination | 600 kcal: 2 g EPA + 40 g protein CNT = isocaloric supplement |
6 weeks | N-3: weight maintenance, ↓CRP, TNFα and IFNγ Control: weight loss (2.0 ± 3.7 lbs), ↓ CRP, ↑ TNFα and IFNγ |
2018 [18] |
| Colorectal (IV) |
23 8 F/13 M |
Age = 61 ± 11.6 Body weight = 75.9 ± 17.0 BMI = 28 ± 6.4 |
Chemotherapy 17 with previous chemotherapy |
600 kcal: 2.2 g EPA + 0.92 g DHA + 32 g protein CNT = N/A |
9 weeks | N-3: ↓ in GM-CSF, ↑ RANTES, CRP (week 3) ↑ in GM-CSF and NC CRP (compared to baseline; week 9), Correlations between baseline IL-10 and survival, IL-6 and survival, IL-6 and CRP |
2007 [41] |
| Colorectal (IV) |
13 (5/6) 4 F/9 M |
Age = 61.5 ± 15.8/68.2 ± 15.6 Body weight = 69.9 ± 15.9/72.2 ± 11.7 BMI = 25.8 ± 4.3/26 ± 3.3 |
Fluorouracil + oxaliplatin + folinic acid or capecitabine | 600 kcal: 2 g EPA + 0.9 g DHA + 32 g protein CNT = N/A |
12 weeks | N-3: ↑ weight, NS improvement in QOL and appetite, NS ↓ in fatigue and pain | 2010 [37] |
| Gastric (I–IV) |
68 24 F/44 M |
Age = 58 Body weight= 63.5 (58.1–69.8)/66.1 (71.7–75.4) BMI = 24.2 (20.4–26.3)/22.8 (20.1–28.3) |
Not stated | 600 kcal: 2 g EPA + 1.2 g DHA + 24 g protein CNT = isocaloric supplement |
30 days | N-3: ↑ weight and ↓ IL-6 compared to control | 2018 [31] |
| Gastrointestinal | 42 15 F/27 M |
Age = 68.1/66.7 Body weight = 69.1/67.8 |
Surgery | 10.5% n-3 of 25% fat + 5.6 g protein in 100 mL (patients received 25 kcal/kg body weight) | 16 days postoperative | N-3: NC in albumin, transferrin, prealbumin, PHA; ↑ stimulated IFN, CD3+, CD3 + HLA-DR, CD4+ and B lymphocytesBoth groups: ↓ T lymphocytes (preoperative to postoperative) | 1995 [38] |
| Gastrointestinal (Advanced) |
24 10 F/14 M |
Age = 66 ± 9/69 ± 10 Body weight = 56.6(35–101)/61.8(33–80) BMI = 21.6 ± 4.1/21.1 ± 4.8 All had >10% weight loss in past 6 months |
Palliative (at least 2 rounds of chemotherapy before study entry) | 4.9 g EPA and 3.2 g DHA± melatonin CNT = isocaloric supplement |
4 weeks | N-3: 38% had weight maintenance, No statistically significant changes in cytokines | 2005 [39] |
| Gastrointestinal (II–IV) |
128 38 F/90 M |
Age = 72.3 ± 8.4/68.9 ± 10.3 Body weight = NS but 5% weight loss before entry |
44 adjuvant chemotherapy/84 palliative chemotherapy | 600 kcal supplement: 2.2 g EPA + 0.92 g DHA + 32 g protein CNT = N/A |
6 months | N-3: stable CRP Control: ↑ CRP |
2017 [64] |
| Lung, Gastrointestinal (I–IV) |
69 28 F/21 M |
Age = 63.5 ± 11.8 BMI = not stated but 87% moderate or severe malnutrition |
Chemotherapy | 600 kcal: 2.2 g EPA 33 g protein CNT = isocaloric supplement |
4 weeks | N-3: ↓ CRP (NS due to dropouts/death only 18 in N-3 vs. 25 in control for final analysis) | 2014 [40] |
| NSCLC (III) |
40 19 F/21 M |
Age = 58.4 ± 12.0/57.2 ± 8.1 Body weight = 77.1 ± 14.6/64.7 ± 7.4 BMI = 24.8 ± 4.1/23.0 ± 2.4 |
Cisplatin ± docetaxel or± bevacizumab + concurrent radiotherapy | 600 kcal: 2.2 g EPA + 1 g DHA + 32 g protein CNT = isocaloric supplement |
6 weeks | N-3: weight maintenance, NC in CRP, IL-6, TNFp55, albumin and HLA-DR | 2012 [53] |
| NSCLC (III–IV) |
84 (44/40) 49 F/43 M |
Age = 58.8 ± 14/61.1 ± 12.4 Body weight = 60.4 ± 11/64.7 ± 11; BMI = 24.2 ± 3/25.2 ± 4 weight loss before entry = 8.8 ± 8%/7.4 ± 9% |
Paclitaxel and cisplatinum | 300 kcal: 1.1 g EPA + protein CNT = isocaloric supplement |
6 weeks supplement and up to 18 weeks chemotherapy) | N-3: weight maintenance; ↓ CRP, TNFα; ↑ protein intake improved global health status (including fatigue and improved appetite); trend towards progression-free survival Control: weight loss, ↑ neuropathy | 2014 [54] |
| Pancreatic, NSCLC | 7 2 F/5 M |
Age = 55.1 ± 5.0 = Body weight = 77.5 ± 11.5 (12% weight loss in previous 6 months)BMI = 26.8 ± 5.7 |
Gemcitabine ± other | 300 kcal: 1.1 g EPA + 16 g protein CNT = N/A |
8 weeks | N-3: ↑ in protein intake, total energy intake, body weight and QOL | 2004 [55] |
| Pancreatic (II–IV) |
36 (18/18) (+ 6 no cancer controls) |
Age = 64(56–66)/60(54–70) Body weight = 55.0(46.5–60.5)/58.5(47.8–70.7); pre-study weight loss = 17.9% (15.9–20.7)/11.8% (5.6–23.5) |
Palliative | 2 × 610 kcal: 2.2 g EPA + 0.96 g DHA + 32 g protein CNT = N/A |
24 days | Baseline: Cancer patients: ↓ albumin, prealbumin and transferrin; ↑ CRP, fibrinogen, haptoglobin, ceruloplasmin. After intervention: N-3: ↑ albumin, prealbumin, transferrin; ↓ CRP; 1.0 kg weight gain | 1999 [59] |
| Pancreatic (II–IV) |
20 10 F/10 M |
Age = 62 (51–75) Body weight = 55.2 (48.8–61.2); 17.9% (15.9–22.8) weight loss BMI = 19.8 (17.8–21.8) |
Palliative surgical procedures | 2 × 610 kcal: 2.2 g EPA, 0.96 g DHA + 32 g protein CNT = N/A |
3–7 weeks | N-3: weight gain = 1.0 kg at 3 weeks, 2 kg at 7 weeks; ↓ IL-6 in stim PBMCs and ↓ trend IL1β (P = 0.07), NC in TNFα, CRP, unstimulated production of cytokines, or serum concentrations of IL-6, sTNF-RI, sTNF-RII, or sIL-6R and NC leptin; ↑ in fasting insulin | 1999, 2001 [60,61] |
Abbreviations used: BMI, body mass index; CD, cluster of differentiation; CNT, control; CRP, C-reactive protein; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; F, female; g, gram(s); GM-CSF, granulocyte macrophage colony-stimulating factor; HLADR, Human Leukocyte Antigen—DR; IFNγ, interferon gamma; IL, interleukin; Int, intervention group; kcal, kilocalorie; kg, kilogram; M, male; N, number; N/A, not applicable; NC, no change, NS, non-significant; NSCLC, non-small-cell lung cancer; PBMC, peripheral blood mononuclear cell, PGE2, prostaglandin E2; PHA, phytohaemagglutinin; QOL, quality of life; RANTES, regulated on activation, normal T cell expressed and secreted (CCL5); Ref, reference; SF36, short form (36) health survey; TNFα, tumor necrosis factor.