Abstract
Cardiovascular diseases remain a global challenge, and lipid-associated biomarkers can predict cardiovascular events. Extensive research on cardiovascular benefits of omega-3 polyunsaturated fatty acids (n3-PUFAs) is geared towards fish oil supplementation and fish-rich diets. Nevertheless, vegetarianism and veganism are becoming more popular across all segments of society, due to reasons as varied as personal, ethical and religious values, individual preferences and environment-related principles, amongst others. Due to the essentiality of PUFAs, plant sources of n3-PUFAs warrant further consideration. In this review, we have critically appraised the efficacy of plant-derived n3-PUFAs from foodstuffs and supplements upon lipid profile and selected cardiometabolic markers. Walnuts and flaxseed are the most common plant sources of n3-PUFAs, mainly alpha-linolenic acid (ALA), and feature the strongest scientific rationale for applicability into clinical practice. Furthermore, walnuts and flaxseed are sources of fibre, potassium, magnesium, and non-essential substances, including polyphenols and sterols, which in conjunction are known to ameliorate cardiovascular metabolism. ALA levels in rapeseed and soybean oils are only slight when compared to flaxseed oil. Spirulina and Chlorella, biomasses of cyanobacteria and green algae, are important sources of n3-PUFAs; however, their benefits upon cardiometabolic markers are plausibly driven by their antioxidant potential combined with their n3-PUFA content. In humans, ALA is not sufficiently bioconverted into eicosapentaenoic and docosahexaenoic acids. However, evidence suggests that plant sources of ALA are associated with favourable cardiometabolic status. ALA supplementation, or increased consumption of ALA-rich foodstuffs, combined with reduced omega-6 (n6) PUFAs intake, could improve the n3/n6 ratio and improve cardiometabolic and lipid profile.
Cardiovascular diseases remain a global challenge, and lipid-associated biomarkers can predict cardiovascular events. Extensive research on cardiovascular benefits of omega-3 polyunsaturated fatty acids (n3-PUFAs) is geared towards fish oil supplementation and fish-rich diets. Nevertheless, vegetarianism and veganism are becoming more popular across all segments of society, due to reasons as varied as personal, ethical and religious values, individual preferences and environment-related principles, amongst others. Due to the essentiality of PUFAs, plant sources of n3-PUFAs warrant further consideration. In this review, we have critically appraised the efficacy of plant-derived n3-PUFAs from foodstuffs and supplements upon lipid profile and selected cardiometabolic markers. Walnuts and flaxseed are the most common plant sources of n3-PUFAs, mainly alpha-linolenic acid (ALA), and feature the strongest scientific rationale for applicability into clinical practice. Furthermore, walnuts and flaxseed are sources of fibre, potassium, magnesium, and non-essential substances, including polyphenols and sterols, which in conjunction are known to ameliorate cardiovascular metabolism. ALA levels in rapeseed and soybean oils are only slight when compared to flaxseed oil. Spirulina and Chlorella, biomasses of cyanobacteria and green algae, are important sources of n3-PUFAs; however, their benefits upon cardiometabolic markers are plausibly driven by their antioxidant potential combined with their n3-PUFA content. In humans, ALA is not sufficiently bioconverted into eicosapentaenoic and docosahexaenoic acids. However, evidence suggests that plant sources of ALA are associated with favourable cardiometabolic status. ALA supplementation, or increased consumption of ALA-rich foodstuffs, combined with reduced omega-6 (n6) PUFAs intake, could improve the n3/n6 ratio and improve cardiometabolic and lipid profile.
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Key points
Studies on the potential efficacy of plant-derived n3-PUFAs in heart disease become further justified as dramatic reductions of fish stocks have been reported in the North Atlantic Ocean and Mediterranean Sea. The present review, critically appraised the efficacy of plant-derived n3-PUFAs from foodstuffs, as well as its supplementation, upon the modulation of lipid profile and selected cardiometabolic markers.
Flaxseed is an important source of ALA, and a few trials have identified beneficial effects of flaxseed intake upon lipid indexes and cardiometabolic biomarkers. In a study recruiting 21 patients with coronary artery disease, a pivotal population to ascertain the magnitude of a cardiometabolic intervention, the daily consumption of 30 g flaxseed for 12 weeks promoted better outcomes as compared to the control group in increasing flow-mediated dilation (5.1 vs. −0.55% change from baseline for the flaxseed and control groups, respectively), whilst decreasing the inflammatory status by reducing the levels of CRP (−1.18 mg/L), IL-6 (−7.65 pg/mL), and TNF-α (−34.73 pg/mL). Importantly, no significant change in body weight was observed in either groups which appears to be a very relevant result as it suggests that flaxseed may improve cardiovascular parameters independently of weight loss.
In a systematic review and meta-analysis of RCTs with 1502 patients across 32 studies, flaxseed or its derivatives (whole or ground flaxseed, flaxseed oil, or lignan supplements) reduced the concentrations of hs-CRP (weighted mean difference (WMD): −0.75; 95% CI −1.19, −0.31) and TNF-α (WMD: −0.38; 95% CI −0.75, −0.01) but did not change IL-6 levels. Flaxseed was tested in the form of whole flaxseed, golden flaxseed, flaxseed oil, and lignan supplements at dosages ranging from 360 mg to 60 g, for 2 to 12 weeks, with an averaged intervention period of approximately 10 weeks.
A recently published clinical trial recruited 41 women suffering with polycystic ovary syndrome, randomly segregated into two groups, group 1 subjected to lifestyle changes (American Heart Association recommendations + >30 min moderate to intense activity 3x/week) plus 30 g/day brown flaxseed flour in salad, yogurt or cold drinks, and group 2 subjected to the same lifestyle changes only, for 12 weeks. The authors found that the flaxseed group showed significant improvements in insulin, homeostasis model assessment of insulin resistance (HOMA-IR), TG, hs-CRP, IL-6, leptin, HDL-C and adiponectin, as compared to the non-flaxseed group.
In a RCT recruiting 100 eligible patients suffering with non-alcoholic fatty liver disease (NAFLD), Yari et al. found that 30 g flaxseed daily plus positive lifestyle interventions for 12 weeks decreased serum concentrations of total cholesterol (TC) (−31.71 mg/dL), TG (−61.33 mg/dL), LDL-C (−22.64 mg/dL), ALT (−11.12 U/L), AST (−5.37 U/L) and gamma-glutamyltransferase (−11.54 U/L), results that were not matched in the group submitted to positive lifestyle interventions only. It should be noted however that both groups showed reductions in BMI (30.37 ± 4.42 to 28.05 ± 3.89 kg/m2 in the flaxseed plus lifestyle improvement group, and 33.37 ± 5.56 to 32.42 ± 5.98 in the lifestyle improvement only group) as well as the intensity of hepatic steatosis, a result most likely attributed to decreased energy intake in both groups (2379.41 ± 473.74 to 2117.47 ± 378.46, and 2424.45 ± 470.89 to 1966.39 ± 449.52 kcal, respectively).
Flaxseed Oil: A RCT investigated the effects of either 25 mL/d flaxseed oil or 25 mL/d sunflower oil administered for seven weeks to 60 patients suffering with metabolic syndrome. Serum IL-6 levels decreased significantly in both groups (9.37 to 7.90 pg/mL, p < 0.001 for flaxseed oil, and 9.22 to 8.48 pg/mL, p < 0.006 for sunflower oil), but the flaxseed oil group presented a greater reduction (p = 0.017). Given that that was a dosage considered high, it is worth mentioning that no side effects were reported in either group. Interestingly, in a study recruiting 60 women with gestational diabetes, the daily supplementation for 6 weeks with 2 g/day flaxseed oil capsules, which contained 800 mg/day ALA, reduced the concentrations of TG (−40.5 mg/dL), TC (−22.7 mg/dL), insulin (−2.2 µIU/mL), and hs-CRP (−1.3 mg/L), as compared to a matched group that received sunflower oil capsules. The flaxseed oil-receiving group also showed upregulated LDL receptor, downregulated IL-1 and TNF-α gene expression, decreased malondialdehyde levels and increased total nitrite and total glutathione levels.
In a recent study recruiting 59 overweight and obese adults with stage I hypertension without pharmacological treatment, 10 g of refined cold-pressed flaxseed oil (4.7 g ALA) for 12 weeks decreased fasting free fatty acid (−58 μmol/L) and TNF-α (−0.14 pg/mL) plasma concentrations. In contrast, no changes were found in other metabolic risk markers (e.g., serum glucose and TG levels) nor vascular function markers (e.g., brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, and retinal microvascular calibres) before versus after testing, both on fasting and postprandially.
Further clinical research is required to broaden the current knowledge of the potential of ALA upon cardiometabolic dysregulations and cardiometabolic protection. Well-designed RCTs could certainly minimize the residual confounding variables caused by other nutrients. In case of suspected insufficient n3 status, such as in individuals with low intake of fatty fish, those who do not take FO supplement, and in vegan individuals with very narrow dietary habits, alternative plant sources of n3-PUFAs may be candidates for partially attending the n3 metabolic demands. Not only ALA in isolation, but its proposed effect in combination with other plant fatty acids and other plant components such as fibre, potassium, magnesium, and non-essential substances, e.g., polyphenols and sterols, may be the players in yielding benefits in cardiovascular metabolism. Consumption of walnuts and flaxseed seems to be the main plant sources of n3-PUFAs with strong scientific basis for translation into clinical practice. Regarding oil intake, we believe that flaxseed oil is more advantageous than walnut oil, because the former’s ALA content is five times greater than that of the latter, which in turn, can be considered the second principal source of ALA. Although several studies have alluded to rapeseed and soybean oils as ALA sources, their ALA amount is slight when compared to flaxseed oil, so that a usual oil serving must be considered in order not to exceed the daily energy requirement in an attempt to achieve an optimal level of ALA.