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

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

The Effect of Ginseng (The Genus Panax) on Glycemic and Vascular Health

The objective was to conduct a systematic review and meta-analysis of RCTs to assess ginseng's effect on glycemic control and further undertake a RCT to explore the therapeutic potential of the economically-grown, non-steamed Korean ginseng variety, Korean white ginseng (KWG). The meta-analysis of 16-trials (n=770) showed that ginseng significantly improved fasting blood glucose relative to control (P=0.03), with no effect on other glycemic parameters. The RCT in 25-subjects with type-2-diabetes revealed that acute administrations of 1g, 3g, and 6gKWG were safe, but did not improve postprandial glycemia and blood pressure measures relative to control. Nevertheless, 3gKWG demonstrated significant improvements in augmentation index compared to control (P=0.04). Overall, the meta-analysis results indicate that ginseng may serve as an adjunct to conventional diabetes therapy. The clinical findings further suggest that KWG may possess promising vascular benefits, offering a potential cost-effective natural health alternative. However, these results are preliminary and warrant long-term exploration.M.Sc

Flavonoid Intake and MRI Markers of Brain Health in the Framingham Offspring Cohort.

BACKGROUND: Although greater flavonoid intake is associated with a reduced risk of Alzheimers disease (AD) and related dementias (ADRD), evidence relating dietary flavonoid intake to brain health based on MRI is lacking. OBJECTIVE: The objective of this study was to explore the association between dietary flavonoid intake and MRI measures of brain health, including total brain tissue volume (TBV), white matter hyperintensities volume (WMHV), and hippocampal volume (HV). METHODS: Eligible subjects included members of the Framingham Heart Study Offspring Cohort who were free of stroke at exam 7 and had at least 1 valid food frequency questionnaire from exams 5, 6, or 7 (n&nbsp;=&nbsp;2086; mean age at exam 7, 60.6 y). Flavonoid intakes represented the cumulative mean of intakes across the 3 exams and were categorized based on quartiles categories of intake. TBV, WMHV, and HV were assessed at exam 7. Multiple linear regression models were used to examine the cross-sectional association between total and the 6 classes of flavonoids and the 3 aforementioned MRI measures. RESULTS: The mean (95% CI) of the WMHV of subjects in the highest quartile category of flavan-3-ols [0.56 (0.52, 0.61)] and flavonoid polymers [0.57 (0.52, 0.61)] intake was significantly smaller relative to that of subjects in the lowest quartile category of flavan-3-ols [0.65 (0.60, 0.71)] and flavonoid polymers [0.66 (0.60, 0.71)] after accounting for important demographic, lifestyle, and clinical factors. Inverse trend associations with WMHV were also seen for flavan-3-ols (P&nbsp;=&nbsp;0.01) and flavonoid polymers (P&nbsp;=&nbsp;0.01) as well as for total flavonoids (P&nbsp;=&nbsp;0.01). TBV and HV were not associated with dietary flavonoid intake following the adjustment for potential confounders. CONCLUSIONS: Our results contribute to the literature on flavonoids and ADRD as they suggest that higher flavonoid intakes may affect ADRD risk in middle-aged and older adults by reducing WMHV, a marker strongly associated with ADRD

The effect of ginseng (the genus panax) on glycemic control: a systematic review and meta-analysis of randomized controlled clinical trials.

Despite the widespread use of ginseng in the management of diabetes, supporting evidence of its anti-hyperglycemic efficacy is limited, necessitating the need for evidence-based recommendations for the potential inclusion of ginseng in diabetes management.To elucidate the effect of ginseng on glycemic control in a systematic review and meta-analysis of randomized controlled trials in people with and without diabetes.MEDLINE, EMBASE, CINAHL and the Cochrane Library (through July 3, 2013).Randomized controlled trials ≥30 days assessing the glycemic effects of ginseng in people with and without diabetes.Relevant data were extracted by 2 independent reviewers. Discrepancies were resolved by consensus. The Heyland Methodological Quality Score and the Cochrane risk of bias tool were used to assess study quality and risk of bias respectively.Sixteen trials were included, in which 16 fasting blood glucose (n = 770), 10 fasting plasma insulin (n = 349), 9 glycated hemoglobin (n = 264), and 7 homeostasis model assessment of insulin resistance (n = 305) comparisons were reported. Ginseng significantly reduced fasting blood glucose compared to control (MD =  -0.31 mmol/L [95% CI: -0.59 to -0.03], P = 0.03). Although there was no significant effect on fasting plasma insulin, glycated hemoglobin, or homeostasis model assessment of insulin resistance, a priori subgroup analyses did show significant reductions in glycated hemoglobin in parallel compared to crossover trials (MD = 0.22% [95%CI: 0.06 to 0.37], P = 0.01).Most trials were of short duration (67% trials<12wks), and included participants with a relatively good glycemic control (median HbA1c non-diabetes = 5.4% [2 trials]; median HbA1c diabetes = 7.1% [7 trials]).Ginseng modestly yet significantly improved fasting blood glucose in people with and without diabetes. In order to address the uncertainty in our effect estimates and provide better assessments of ginseng's anti-diabetic efficacy, larger and longer randomized controlled trials using standardized ginseng preparations are warranted.ClinicalTrials.gov NCT01841229

Forest plots of controlled clinical trials investigating the effect of ginseng on homeostasis model assessment of insulin resistance.

<p>The diamond represents a pooled effect estimate. Paired analyses were applied to all crossover trials <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Elbourne1" target="_blank">[18]</a>. Data are mean differences (MD) with 95% CI. <i>P</i> values are for Generic Inverse Variance random effects models. Inter-study heterogeneity was tested by the Cochran Q statistic at a significance level of <i>P</i> <0.10 and quantified by the I² statistic, where I² ≥ 50% is considered to be evidence of substantial heterogeneity.</p

Flow of the literature search for the effect of ginseng on glycemic outcomes (FBG, FPI, HbA1c, and HOMA-IR).

<p>Flow of the literature search for the effect of ginseng on glycemic outcomes (FBG, FPI, HbA1c, and HOMA-IR).</p

Forest plots of controlled clinical trials investigating the effect of ginseng on glycated hemoglobin.

<p>The diamond represents a pooled effect estimate. Paired analyses were applied to all crossover trial <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Elbourne1" target="_blank">[18]</a>. Data are mean differences (MD) with 95% CI. <i>P</i> values are for Generic Inverse Variance random effects models. Inter-study heterogeneity was tested by the Cochran Q statistic at a significance level of <i>P</i> <0.10 and quantified by the I² statistic, where I² ≥ 50% is considered to be evidence of substantial heterogeneity.</p

Characteristics of Studies Investigating the Effect of Ginseng on Glycemic Outcomes.

<p>Abbreviations: T1DM – Type 1 Diabetes mellitus; T2DM – Type 2 Diabetes mellitus; Pre-DM – Pre-diabetes Mellitus; EHPT – Essential hypertension; F – Female; M – Male; BMI – Body mass index; C – Control group; T – Treatment group; T1 – Treatment group #1; T2 – Treatment group #2; T3 – Treatment group #3; IP – Inpatient; OP – Outpatient; MQS – Heyland Methodological Quality Score; N/R – Not reported.</p><p>*Studies by Sotaniemi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Sotaniemi1" target="_blank">[7]</a>, Yoon et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Yoon1" target="_blank">[30]</a>, and Reeds et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Reeds1" target="_blank">[25]</a> contained multiple comparisons, and to mitigate unit-of-analysis error, we combined groups to create a single pairwise comparison.</p>†<p>Pre-DM included subjects with either Impaired Fasting Glucose or Impared Glucose Tolerance.</p>‡<p>Pre-study baseline BMI is listed. The study by Rhee et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Rhee1" target="_blank">[26]</a> did not report SD for the mean BMI of participants.</p>§<p>Pre-study baseline endpoints are listed. In studies were these values were not reported, the start value of control was assumed to be equivalent to baseline and was reported. Where start of control value was not given, of control value was assumed to be equivalent to baseline and was reported. Assumed values are reported in bold. The study by Reay et al. (a) & (b) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Reay1" target="_blank">[24]</a> used n = 23 and n = 14 respectively for reporting data on fasting blood glucose, n = 17 and n = 12 respectively for reporting data on fasting plasma insulin, and n = 18 and n = 11 respectively for reporting data on HbA1c.</p><p>∥Ginseng dose is reported individually for trials with multiple treatment groups.</p>¶<p>All ginseng doses were compared to placebo, a control group that did not receive ginseng, or fermented soybean.</p><p>**Study quality was assessed by the Heyland Methodological Quality Score (MQS) and trials with a score ≥ 8 were considered to be of high quality.</p>††<p>Agency funding is that from government, university or not-for-profit health agency sources. None of the trialists declared conflicts of interest.</p><p>All data is expressed as mean ± SD.</p><p>Characteristics of Studies Investigating the Effect of Ginseng on Glycemic Outcomes.</p