Comparisons of the effects of different flaxseed products consumption on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases: systematic review and a dose–response meta-analysis of randomized controlled trials

Yang, Chao; Xia, Hui; Wan, Min; Lu, Yifei; Xu, Dengfeng; Yang, Xian; Yang, Ligang; Sun, Guiju

doi:10.1186/s12986-021-00619-3

Table 2 Demographic characteristics and baseline parameters of the 33 studies selected for analysis

From: Comparisons of the effects of different flaxseed products consumption on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases: systematic review and a dose–response meta-analysis of randomized controlled trials

References	Country	Completer/enrollment	Patient features ()	Dyslipidemia state	Age [Mean (SD) or range]	Design	Intervention	WF (g/d)	FLO (g/d)	LIG (g/d)	Duration (weeks)
Patients with NAFLD
Rezaei et al. [47]	Iran	57/68	Patients with NAFLD; BMI ≥ 25 (FLO: 30.1 ± 4.1; SFO: 29.6 ± 3.9) kg/m²; Gender: Mixed	Marginal hypertriglyceridemia; TG (FLO: 1.9 ± 1.6; SFO: 1.71 ± 0.99) mmol/L	FLO: 45.5 (8.7) SFO: 40.8 (8.7)	RCT^a	FLO/ SFO	NA	20 ml/d	NA	12 weeks
Yari et al. [48]	Iran	50/52	Patients with NAFLD; BMI: 30.72 ± 3.31 kg/m²; Gender: Mixed	Hypertriglyceridemia; TG: 215.26 ± 85.68 mg/dL	45.02 (10.44)	RCT^a	LC + brown milled flaxseed/ LC	30 g	NA	NA	12 weeks
Patients with Atherosclerosis
Raygan et al. [51]	Iran	55/60	T2DM patients with CHD; BMI: < 25 and ≥ 25 kg/m²; Gender: Mixed	Non dyslipidemia	FLO: 64.1 (9.3) Con: 64.6 (9.1)	RCT^a	FLO /paraffin	NA	1 g*2 (ALA: 0.4 g)	NA	12 weeks
Edel et al. [34]	Canada	84/110	Patient with peripheral artery disease; BMI: Not reported; Gender: Mixed	Non dyslipidemia	Not reported	RCT^a	Milled flaxseed/ whole wheat	30 g	NA	NA	12 moths
Patients with MetSyn
Akrami et al. [52]	Iran	52/60	Patients with MetSyn; Weight (FLO: 81.17 ± 11.23, SFO: 84.50 ± 14.89) kg; WC (FLO: 99.42 ± 6.95, SFO: 101.85 ± 10.73) cm; Gender: Mixed	Marginal hyperlipidemia; (HDL < 40 mg/dL for men and < 50 mg/dL for women, TG ≥ 150 mg/dL)	FLO: 48.3 (6.9) SFO: 48.8 (6.4)	RCT^a	FLO/SFO	NA	25 ml/d	NA	7 weeks
Yari et al. [49]	Iran	44/60	Patients with MetSyn; BMI: 30.90 ± 3.39 kg/m²; Gender: Mixed	Hypertriglyceridemia; TG: 217.6 ± 86.44 mg/dL	Flax: 45.8 (10.9) Con: 45.2 (10.3)	RCT^a	Brown milled flaxseed + LC/ LC	30 g	NA	NA	12 weeks
Wu et al. [28]	China	189/189	Patients with MetSyn; BMI (LC: 25.4 ± 2.4, LCF: 25.1 ± 2.3) kg/m²; Gender: Mixed	Hyperlipidemia; TC (LC: 6.1 ± 1.7, LCF: 6.0 ± 1.5) mmol/L; LDL-C (LC: 4.3 ± 1.4, LCF: 4.2 ± 1.3) mmol/L; TG (LC: 1.94 [1.45–2.80], 1.89 [1.36–2.77]) mmol/L	25–65	RCT^a	LC + flaxseed/LC	30 g	NA	NA	12 weeks
Patients with Dyslipidemia
Torkan et al. [50]	Iran	70/70	Patients with hyperlipidemia; BMI (Flax: 27.28 ± 0.61; Con: 27.68 ± 0.43) kg/m²; Gender: Mixed	Hyperlipidemia TC (Flax: 226 ± 6.2, Con: 214.8 ± 5.7) mg/dL; TG (Flax: 226.05 ± 18.7, Con: 213 ± 15.6) mg/dL	Flax: 43.4 (1.1) Con: 40.5 (1.4)	RCT^a	Raw flaxseed powder/NR	30 g	NA	NA	5.7 weeks (40 days)
Cassani et al. [40]	Brazil	27/27	Men with cardiovascular risk factors; WC ≥ 90 cm; BMI (Flax: 32 ± 3, Con: 32.1 ± 2.8) kg/m²; Gender: Men	Hyperlipidemia; TC ≥ 200 mg/dL, LDL-C ≥ 130 mg/dL, HDL-C < 40 mg/dL, TG ≥ 150 mg/dL	Flax: 40 (9) Con: 33 (10)	RCT^a	Brown flaxseed powder/rice raw powder	60 g	NA	NA	6 weeks
Dittrich et al. [45]	Germany	49/59	Patients with moderate hypertriglyceridemia; BMI (SFO: 28.35 ± 4.25, FLO: 28.10 ± 3.84) kg/m²; Gender: Mixed	Moderate hypertriglyceridemia; TG > 1.5 mmol/L	56 (12)	RCT²	FLO/SFO	NA	10 g/d (ALA: 7 g)	NA	10 weeks
Saxena et al. [46]	India	50/50	Patients with dyslipidemia; BMI (Flax: 28.48 ± 2.91, Con: 28.90 ± 4.21) kg/m²; Gender: Mixed	Hyperlipidemia; TG > 150 mg/dL; TC > 200 mg/dL; LDL-C > 130 mg/dL	40–60	RCT^a	Roasted flaxseed powder /NR	30 g	NA	NA	3 moths
Soltani et al. [53]	Iran	30/38	Hemodialysis patients with dyslipidemia; BMI (Flax: 25.5 ± 2.0, Con: 27.0 ± 1.0) kg/m²; Gender: Mixed	Hyperlipidemia; TG > 200 mg/dL and/or HDL-C < 40 mg/dL	Flax: 54.0 (4.0) Con: 54.5 (4.0)	RCT^a	Ground flaxseed/usual diet	40 g	NA	NA	8 weeks
Gillingham et al. [35]	Canada	36/39	Subjects with hypercholesterolemia; BMI: 28.56 ± 4.62 kg/m²; Gender: Mixed	Hypercholesterolemia; LDL-C > 3.0 mmol/L	47.49 (11.93)	RCT²	HOCO + FLO/HOCO	NA	NA	NA	4 weeks
Fukumitsu et al. [20]	Japan	16/20	Men with moderately hypercholesterolemic; BMI (LIG: 23.5 ± 1.0, 23.8 ± 1.2; Con: 25.5 ± 1.7) kg/m²; Gender: Men	Hypercholesterolemia 4.65 ≤ TC ≤ 6.21 mmol/L (180–240 mg/mL)	21–57	RCT^a	LIG/placebo (corn starch)	NA	NA	0.02	12 weeks
Fukumitsu et al. [20]	Japan	16/20			21–57	RCT^a	LIG/placebo (corn starch)	NA	NA	0.1	12 weeks
Zhang et al. [19]	China	35/44	Men and women with hypercholesterolemia; BMI: 26–27 kg/m²; Gender: Mixed	Hypercholesterolemia; LDL-C ≥ 3.62 mmol/L	53.5–58.3	RCT^a	LIG/placebo (maltodextrin)	NA	NA	0.3	8 weeks
Zhang et al. [19]	China	37/44		Hypercholesterolemia; LDL-C ≥ 3.62 mmol/L	53.5–58.3	RCT^a	LIG/placebo (maltodextrin)	NA	NA	0.6	8 weeks
Bloedon et al. [23]	US	50/62	Men and post-menopausal women with hypercholesterolemia; BMI: (Flax: 27.4 ± 4.4, Con: 28.1 ± 5.1) kg/m²; Gender: Mixed	Hypercholesterolemia; LDL-C of 130–200 mg/dL, TG < 600 mg/dL	44–75	RCT^a	Flaxseed/wheat bran	20 g	NA	NA	5 weeks
Bloedon et al. [23]	US	50/62			44–75	RCT^a	Flaxseed/wheat bran	20 g	NA	NA	10 weeks
Patade et al. [30]	US	26/37	Postmenopausal women with hypercholesterolemia (moderate); BMI: Not reported. Gender: Woman	Hypercholesterolemia; TC: ≥ 5.1 to ≤ 9.8 mmol/L	47–63	RCT^a	Flaxseed/muffins and white bread	30 g	NA	NA	3 moths (12.9 weeks)
Paschos et al. [37]	Greece	87/87	Men with dyslipidemia; BMI (FLO: 28 ± 3, SAO: 28 ± 4) kg/m²; Gender: Men	Hyperlipidemia; TC > 200 mg/dL, and/or HDL-C < 40 mg/dL	SAO: 52.0 (1.0) FLO: 54.1 (1.6)	RCT^a	FLO/SAO	NA	15 ml/d (ALA: 8 g)	NA	12 weeks
Rallidis et al. [39]	Greece	76/90	Men with dyslipidemia; BMI: (ALA: 28.42 ± 3.44, 28 ± 3.19) kg/m²; Gender: Men	Hyperlipidemia; TC (ALA: 232 ± 34, LA: 234 ± 46) mg/dL; LDL-C (ALA: 154 ± 37, LA: 154 ± 43) mg/dL; TG (ALA: 155 ± 84, LA: 173 ± 113) mg/dL	ALA: 50.4 (7.3) LA: 52.0 (7.7)	RCT^a	Linseed oil/LA	NA	15 ml/d (ALA: 8.1 g)	NA	12 weeks
Rallidis et al. [38]	Greece	76/90	Men with dyslipidemia; BMI: (ALA: 28.42 ± 3.44, 28 ± 3.19) kg/m²; Gender: Men	Hyperlipidemia; TC (ALA: 232 ± 34, LA: 234 ± 46) mg/dL; LDL-C (ALA: 154 ± 37, LA: 154 ± 43 mg/ dL); TG (ALA: 155 ± 84, LA: 173 ± 113 mg/ dL)	ALA: 50.4 (7.3) LA: 52.0 (7.7)	RCT^a	Linseed oil//SAO	NA	15 ml/d (ALA: 8 g)	NA	12 weeks
Jenkins et al. [36]	Canada	29/37	Men and postmenopausal women with hyperlipidemia; BMI (24.9 ± 0.5 [mean ± SEM]; range: 19.6–29.8) kg/m²; Gender: Mixed	Hyperlipidemia; [LDL-C > 4.1 mmol/L (160 mg/dL) or TG > 2.3 mmol/L (200 mg/dL)]	57 (2)	RCT^a	Defatted flaxseed/wheat bran	50 g	NA	NA	3 weeks
Arjmandi et al. [31]	US	34/38	Postmenopausal women with hypercholesterolemia; Gender: Woman	mild, moderate, or severely hypercholesterolemia; (5.85–9.05) mmol/L	56.3 (6.5)	RCT^a	WF/ sunflower seed	68 g	NA	NA	6 weeks
Bierenbaum et al. [32]	US	15/15	Subjects with hypercholesterolemia; None were excessively overweight (mean 154 ± 4.8 lbs); Gender: Mixed	Hypercholesterolemia TC > 240 mg/dL	52.2 (1.8)	RCT²	VE + Flaxseed powder/VE	15 g	NA	NA	12 weeks
Subjects with overweight or obese
Yang et al. [29]	China	66/73	Hypertensive comorbid with abdominal obesity; BMI (FLO: 26.83 ± 3.06, CO: 26.78 ± 2.98) kg/m²; WC (97.42 in men, 95.74 in women) cm; Gender: Mixed	Non dyslipidemia	FLO: 56.6 (7.8) CO: 58.4 (6.87)	RCT^a	FLO/ corn oil	NA	4 g/d (ALA: 2.5 g)	NA	13 weeks/90 days
de Oliveira et al. [41]	Brazil	76/79	Obese or overweight non-Diabetic elderly patients; BMI ≥ 27 (FLO: 32.7 ± 4.62, OO: 34.4 ± 3.97) kg/m²; Gender: Mixed	Not reported	FLO: 66.3 (4.62) SFO: 68.0 (5.69)	RCT^a	FLO/SFO	NA	30 ml/d (ALA: 24 g)	NA	13 weeks/90 days
Brahe et al. [44]	Denmark	35/40	Obese postmenopausal women; BMI: 30–45 kg/m²; Gender: Woman	Hyperlipidemia TC (6.36 ± 0.89, 6.13 ± 1.06) mmol/L; LDL-C (4.11 ± 0.84, 3.73 ± 0.84) mmol/L	Flax: 60.6 (6.4) Con:5 8.5 (5.3)	RCT^a	Flaxseed mucilage/ Placebo buns	10 g	NA	NA	6 weeks
Machado et al. [22]	Brazil	61/75	Overweight adolescents; BMI: (Flax: 23.38 ± 2.33, Co: 23.71 ± 2.01) kg/m²; Gender: Mixed	Non dyslipidemia	13.7 (2.1)	RCT^a	Brown flaxseed/wheat bran	28 g	NA	NA	11 weeks
Machado et al. [22]	Brazil	61/75		Non dyslipidemia	13.7 (2.1)	RCT^a	Golden flaxseed/wheat bran	28 g	NA	NA	11 weeks
Hutchins et al. [21]	US	25/41	Overweight or obese men and postmenopausal women; BMI: 30.4 ± 5.3 kg/m²; Gender: Mixed	Not reported	Men: 56.9 (8.3) Women: 60.0 (4.1)	RCT^b	Flaxseed powder/non- flaxseed	13 g	NA	NA	12 weeks
Hutchins et al. [21]	US	25/41		Not reported	Men: 56.9 (8.3) Women: 60.0 (4.1)	RCT^b	Flaxseed powder/non- flaxseed	26 g	NA	NA	12 weeks
Rhee et al. [33]	US	9/11	Obese glucose intolerant people; BMI (Flax: 32.4 ± 8.2, Con: 32.0 ± 8.3) kg/m²; Gender: Mixed	Not reported	54.7 (6)	RCT^b	Flaxseed powder/wheat bran	40 g	NA	NA	12 weeks
Faintuch et al. [43]	Brazil	18/20	Subjects with morbidly obese; BMI (44.0 ± 3.9, 45.2 ± 4.2) kg/m²; Gender: Mixed	Non dyslipidemia	Flax: 47.8 (8.0) Con: 50.7 (6.4)	RCT^a	Flaxseed powder/cassava powder	60 g	NA	NA	12 weeks
Faintuch et al. [42]	Brazil	24/24	Subjects with morbidly obese; BMI (Flax: 47.1 ± 7.2, Con: 47.2 ± 7.2) kg/m²; Gender: Mixed	Non dyslipidemia	40.8 (11.6)	RCT^a	Flaxseed flour/manioc flour	30 g	NA	NA	2 weeks

US, United States; UK, United Kingdom ; TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; FLO, flaxseed oil; FO, fish oil; CO, corn oil; HPO, hempseed oil; OO, olive oil; SFO, sunflower oil; SAO, safflower oil; SBO, soybean oil; HORO, high-oleic rapeseed oil; WF, whole flaxseed; LIG, flaxseed lignan; HOCO, novel high-oleic rapeseed (canola) oil; LC, lifestyle counseling; VE, Vitamin E; NAFLD, nonalcoholic fatty liver disease; T2DM, Type 2 diabetic mellitus; CHD, coronary heart disease; MetSyn, metabolic syndrome; WC, waist circumference
^aa randomized clinical trial
^ba randomized crossover study

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