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Review
. 2017 May;96(21):e6531.
doi: 10.1097/MD.0000000000006531.

The Effect of Alpha-Linolenic Acid on Glycemic Control in Individuals With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

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Free PMC article
Review

The Effect of Alpha-Linolenic Acid on Glycemic Control in Individuals With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Elena Jovanovski et al. Medicine (Baltimore). .
Free PMC article

Abstract

Background: Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation.

Methods: The parameters of interest were glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment for insulin resistance (HOMA-IR), fructosamine, and glycated albumin. A comprehensive search was conducted with MEDLINE, Embase, CINAHL, and Cochrane. Eligible studies included randomized controlled trials (RCTs) ≥1 month in duration that compared diets enriched in ALA with usual diets on glycemic parameters. For each study, the risk of bias as well as the study quality was assessed. Using the statistical software RevMan (v5.3), data were pooled using the generic inverse method with random effects model, and final results were expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I statistic.

Results: A total of 8 trials (N = 212) were included in the meta-analysis. Compared to a control diet, a median dose of 4.4 g/day of ALA intake for a median duration of 3 months did not affect HbA1c (%) (MD = -.01; [95%: -.32, .31], P = .96). A median ALA dose of 5.4 g/day did not lower FBG (MD = .07; [95% CI: -.61, .76], P = .84) or FBI (MD = 7.03, [95% CI: -5.84, 19.89], P = .28). Summary effect estimates were generally compromised by considerable and unexplained heterogeneity (I ≥75%). In the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA. Further adjustment for Publication Bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of -.25 (95% CI: -.38, -.12; P <.001) for HbA1c (%).

Conclusions: ALA-enriched diets did not affect HbA1c, FBG, or FBI. The scarce number of existing RCTs and the presence of heterogeneity in our meta-analysis limit the ability to make firm conclusions about ALA in T2DM management. The potential for ALA to have dose-dependent effects warrants further research in this area.

Conflict of interest statement

In the last 5 years, RdS has served as an external resource person to the World Health Organization's Nutrition Guidelines Advisory Group on trans fats and saturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012 to 2015 to present and discuss this work. He has also done contract research for the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has held a grant from the Canadian Foundation for Dietetic Research as a principal investigator, and is a co-investigator on several funded team grants from Canadian Institutes of Health Research. JLS has received research support from the Canadian Institutes of health Research (CIHR), Canadian Diabetes Association (CDA), PSI Foundation, Calorie Control Council, Banting and Best Diabetes Centre (BBDC), American Society for Nutrition (ASN), Dr. Pepper Snapple Group (investigator initiated, unrestricted donation), INC International Nut and Dried Fruit Council, and The Tate and Lyle Nutritional Research Fund at the University of Toronto. He has received speaker fees and/or honoraria from the Canadian Diabetes Association (CDA), Canadian Nutrition Society (CNS), University of Alabama at Birmingham, Abbott Laboratories, Canadian Sugar Institute, Dr. Pepper Snapple Group, The Coca-Cola Company, Dairy Farmers of Canada, Nutrition Foundation of Italy (NFI), C3 Collaborating for Health, White Wave Foods, Rippe Lifestyle, mdBriefcase, Alberta Milk, Food Minds, PepsiCo, and Pulse Canada. He has ad hoc consulting arrangements with Winston & Strawn LLP, Perkins Coie LLP, and Tate & Lyle. He is a member of the European Fruit Juice Association Scientific Expert Panel. He is on the Clinical Practice Guidelines Expert Committees of the Canadian Diabetes Association (CDA), European Association for the study of Diabetes (EASD), and Canadian Cardiovascular Society (CCS), as well as an expert writing panel of the American Society for Nutrition (ASN). He serves as an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Technical Committee on Carbohydrates of the International Life Science Institute (ILSI) North America. He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His wife is an employee of Unilever Canada. VV holds a research grant from CDA for study of dietary intervention including viscous, soluble fibre and holds the Canadian (2,410,556) and American (7,326,404) patent on medical use of viscous fibre blend for reducing blood glucose for treatment of diabetes, increasing insulin sensitivity, reduction of systolic blood pressure and blood lipids. The other authors have no conflicts of interest related to this manuscript.

Figures

Figure 1
Figure 1
PRISMA flow diagram. Search and data selection.
Figure 2
Figure 2
Forest plot of randomized controlled trials investigating ALA on HbA1c (%). Pooled effect estimate (diamond) for HbA1c from 10 trials. Data expressed at MD ± SD, with 95% CIs, using the generic inverse-variance method with random effects model. Between-study heterogeneity quantified by I2 at a significance P <.10. N = number of participants in each treatment group. ALA = alpha-linolenic acid, CI = confidence interval, HbAc1 = glycated hemoglobin, MD = mean difference, SD = standard deviation.
Figure 3
Figure 3
Forest plot of randomized controlled trials investigating ALA on FBG (mmol/L). Pooled effect estimate (diamond) for FBG)from 9 trials. Data expressed at MD ± SD, with 95% CIs, using the generic inverse-variance method with random effects model. Between-study heterogeneity quantified by I2 at a significance P <.10. N = number of participants in each treatment group. ALA = alpha-linolenic acid, CI = confidence interval, FBG = fasting blood glucose, MD = mean difference, SD = standard deviation.
Figure 4
Figure 4
Forest plot of randomized controlled trials investigating ALA on FBI (pmol/L). Pooled effect estimate (diamond) for FBI from 9 trials. Data expressed at MD ± SD, with 95% CIs, using the generic inverse-variance method with random effects model. Between-study heterogeneity quantified by I2 at a significance P <.10. N = number of participants in each treatment group. ALA = alpha-linolenic acid, CI = confidence interval, FBI = fasting blood insulin, HbAc1 = glycated hemoglobin, MD = mean difference, SD = standard deviation.
Figure 5
Figure 5
Funnel plots assessing publication bias. The funnel plots represent a visual assessment of publication bias for the studies investigating ALA on (A). HbA1c (%) (B). FBG (mmol/L) (C). FBI (pmol/L). The solid line represents the pooled summary effect expressed as a weighted MD. The dashed lines represent pseudo 95% CIs. Publication bias and small-study effects were quantitatively assessed using Egger's and Begg's test and presented as P-values. ALA = alpha-linolenic acid, CI = confidence interval, FBG = fasting blood glucose, FBI = fasting blood insulin, HbAc1 = glycated hemoglobin, MD = mean difference.
Figure 6
Figure 6
Funnel Plots for correcting Publication bias using trim-and-fill analysis. Funnel plots for trim-and-fill analysis of (A). HbA1c (%) (B). FBG (mmol/L) (C). FBI (pmol/L). The horizontal line represents the pooled effect estimate expressed as a mean difference, and the diagonal lines represent pseudo-95% CIs of the mean difference. Clear circles represent the effect estimates of the included studies, and the black squares represent the imputed studies. CI = confidence interval, FBG = fasting blood glucose, FBI = fasting blood insulin, HbAc1 = glycated hemoglobin.

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