Whole grain wheat sourdough bread does not affect plasminogen activator inhibitor-1 in adults with normal or impaired carbohydrate metabolism,☆☆

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Abstract

Background and aims

Epidemiological studies suggest whole grain consumption is associated with a reduced risk of cardiovascular disease (CVD), possibly through alterations in glucose metabolism and subsequent effects on plasminogen activator inhibitor (PAI)-1, a novel biomarker for CVD. Our aim was to investigate the effect of 6 wk of whole grain wheat sourdough bread consumption versus refined white bread on PAI-1.

Methods and Results

Normoglycemic/normoinsulinemic (NGI; n = 14; age 53 ± 6 y; BMI 26.5 ± 2.9 kg/m2) and hyperglycemic/hyperinsulinemic (HGI; n = 14; age 57 ± 7 y; BMI 35.7 ± 5.7 kg/m2) adults incorporated whole grain wheat sourdough (162.5 g) or white (168.8 g) bread into their diet, for 6 wk in a randomized crossover study. Pre- and post-intervention, fasting blood samples were analyzed for PAI-1 (primary outcome), as well as glucose, insulin and glucagon (secondary outcomes) at fasting and postprandially after an oral glucose tolerance test (OGTT). Anthropometric measures, fasting glucose, insulin, glucagon and PAI-1 antigen and activity were not different between treatments in either NGI or HGI adults. Glucose incremental area under the curve (iAUC) was lower (19%, P = 0.02) after 6 wk consumption of whole grain wheat sourdough bread compared to white bread in the HGI group, with no differences in insulin or glucagon iAUC in either group.

Conclusion

Our data showed decreased glucose iAUC after an OGTT following 6 wk whole grain wheat bread consumption in adults with differing glycemic/insulinemic status, but no improvements in PAI-1 or fasting glycemic parameters.

Introduction

Alteration in dietary carbohydrate, including increased whole grain intake, is associated with reduced risk of cardiovascular disease (CVD) [1], [2]. Whole grain foods are composed of the bran, germ, and endosperm in the same proportions as the original cereal grain, while refined grains lose a portion of the bran and/or germ during refining [3], [4], producing a product relatively lower in dietary fiber, micronutrients, and phytochemicals, all of which have potential to impact health [3], [4].

Mechanisms by which whole grains exert protective effects remain undetermined [3], [4], but may be through modulation of PAI-1, a CVD biomarker that may be altered by dietary carbohydrates [5], [6], [7], [8]. Elevations in PAI-1, a key regulator of fibrinolysis within the vascular system [9], [10], [11], have been associated with CVD [12], [13], [14], [15], [16]. Studies have demonstrated that different types of carbohydrates can modulate plasma PAI-1. For example, adoption of a low glycemic index (GI) diet for 3 wk in adults with type 2 diabetes (T2D) significantly attenuated circulating PAI-1 [6], [7], along with an associated reduction in postprandial glucose and insulin [6]. While more modest dietary changes, such as the addition of whole grains to the habitual diet, have not been associated with alterations in PAI-1, previous studies have been limited by the use of healthy adults with low baseline PAI-1 activity [8], [17]. No studies to date have examined the impact of a more modest dietary change on PAI-1 in adults with impaired glucose metabolism or hyperinsulinemia. Given the potential for a more modest dose of whole grains to modulate carbohydrate metabolism in adults with metabolic dysregulation [18], [19], we hypothesized that a modest dose of whole grains added to the habitual diet of adults with abnormal glucose tolerance and/or hyperinsulinemia would reduce circulating PAI-1.

Our objective was to investigate the effect of 6 wk whole grain wheat sourdough bread consumption versus refined white bread on PAI-1, the primary outcome measure, in adults with low and high levels of CVD risk. Secondary outcome measures included parameters of postprandial carbohydrate handling that have been associated with PAI-1 regulation.

Section snippets

Study population

Non-smoking women (no menses for ≥ 1y) and men 43–70 y were recruited from Guelph and area. Individuals were excluded if they reported any serious medical condition (e.g. CVD, T2D, hepatic or renal disease, cancer), ≥2 alcohol drinks/d, use of lipid-lowering medication, daily aspirin or hormone replacement therapy, body weight changes >5% within 6 mo, current or planned attempts to lose or gain weight, elite athletic training or gluten allergy. Potential participants underwent a 75 g oral

Baseline and nutrient intake data

Participants were recruited between April 2007 and July 2008 and intention-to-treat analysis was used (Fig. 1). Treatment compliance was 95% as assessed by subject-reported diaries. Subject baseline characteristics are reported in Table 2. Daily intakes of energy and macronutrient intake did not differ between the 3 d before the start of each treatment, within either NGI or HGI (Table 3). As expected, in both groups, total dietary fiber intake was greater (P < 0.01) during the whole grain wheat

Discussion

While studies have consistently shown that whole grain intake is associated with reduced CVD risk, mechanisms are not known [1], [2]. One possibility may be through modulation of PAI-1, although the effect of whole grain and refined wheat bread on PAI-1 has not been previously studied in adults with low and high CVD risk. We hypothesized that whole grain bread would favorably alter PAI-1 in adults with elevated fasting glucose and/or insulin, given their tendency for elevated circulating PAI-1.

Acknowledgements

We acknowledge the participants for their participation, as well as Premila Sathasivam and Mehrnoosh Kashani for technical assistance, and Kendra Brett, Stacey Dundas, Alex Kartes, Rachel Rebry and Laura Willis for help with data collection and sample analysis.

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    Supported by the Ontario Ministry of Agriculture, Food and Rural Affairs and a donation from Stonemill Bakehouse Ltd.

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    Author Disclosures: no conflicts of interest.

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