Effects of Short-Term Consumption of Bread Obtained by an Old Italian Grain Variety on Lipid,Inflammatory,and Hemorheological Variables: An Intervention Study

Abstract

The aim of this study was to evaluate the influence of short-term dietary intake of bread obtained by a selected variety of old grain grown in Tuscany, Italy on some parameters related to the atherosclerotic process. Twenty healthy subjects (median age, 39.5 years) followed for 10 weeks a diet containing bread (150 g/day) made from the test grain (test period) and for the same period a diet containing commercially available bread of the same quantity (control period). Lipid, inflammatory, and hemorheological profiles before and after dietary intervention were evaluated. The test period showed a significant (P < .05) improvement of total cholesterol (pre-intervention, 211.2 ± 10.8 mg/dL; post-intervention, 196.5 ± 9.8 mg/dL) and low-density lipoprotein-cholesterol levels (pre-intervention, 137.5 ± 8.1 mg/dL; post-intervention, 119.5 ± 7.5 mg/dL), whereas no significant changes during the control period were observed. With regard to inflammatory and hemorheological parameters, the test period showed a significant decrease in some of the parameters investigated (interleukin-8 [pre-intervention vs. post-intervention, 67.4 ± 10.7 vs. 43.9 ± 4.1 pg/mL], whole blood viscosity at high [4.36 ± 0.03 vs. 4.32 ± 0.03 mPa · s, respectively] and low [26.1 ± 0.4 vs. 24.8 ± 0.5 mPa · s, respectively] shear rates, and erythrocyte filtration [8.4 ± 0.7% vs. 9.1 ± 0.6%, respectively]) relative to the control period, which showed no significant changes. Short-term dietary intake of whole grain bread obtained from an old grain variety seems to impose a favorable status with regard to lower circulating levels of markers of atherosclerosis.

Introduction

W hole grain products have been reported to have several positive effects on human health.^1,2 All the major scientific associations providing nutritional recommendations to prevent major diseases put carbohydrates in the first place of the pyramid for a health diet.^3,4 The benefits of carbohydrates on the risk of cardiovascular diseases are mostly determined by their structure and content.⁵ Carbohydrate foods contain several nutrients that may reduce risk factors for cardiovascular diseases such as several phenolic acids with antioxidant properties, vitamin E, linoleic acid, and phytoestrogens.⁶ Actually, bread obtained with semi-integral flour produced by “stone mill” and by acid leavening (sourdough) contains a large amount of vitamin B₆ and folic acid, both B-group vitamins. Cereals, and in particular whole wheat products, are an important source of mineral and trace elements such magnesium, iron, zinc, and copper.⁷ These elements are mainly present in the aleuronic layer of bread wheat grains.^8,9

Recently, it has been demonstrated that several beneficial components of cereals depend on the production, storage, processing, and climatic conditions of the source grains.^10,11 Indeed, it has been reported that different varieties of germs contain different levels of B-group vitamins and antioxidants.¹² Thus, the identification of some particular variety of germs determining particular types of cereals rich in these supposed beneficial elements seems to be of importance for optimizing diet for prevention of major chronic diseases. In this regard, old wheat varieties seem to have a more variable composition of these secondary metabolites.¹² In the last 50 years breeding strategies were aimed at improving the yield production, to increase the kernel protein content, and to adapt the wheat plants at a high chemical fertilization input. This led to a progressive abandonment of the old varieties, which are not suitable for the high-input cultivation system. However, the old varieties can be found either in germoplasm collections or in seed savers. In particular, the old Verna variety is actually commercialized in Tuscany.

The aim of this crossover dietary intervention study was, therefore, to assess the possible effects of a mid-term consumption of an old selected grain variety on some atherosclerotic markers such as lipid, inflammatory, and hemorheological profiles.

Materials and Methods

Study population

Twenty clinically healthy subjects (nine women, 11 men) were recruited into a protocol approved by the institutional review board, and all gave informed consent. Participants taking any prescribed medications, food supplements, or following special diets were excluded from the study. Participants were subjects who reported being fond of grain products and willing to undertake a grain product's consumption period. In order to identify symptom-free subjects and to exclude who were suspected of having any form of vascular and inflammatory diseases, a detailed interview addressed to personal and familial history was performed. Current smoking status was determined at the time of physical examination. Body mass index (BMI) was calculated as weight (kg)/height (m)².

The bread used for the experiment was derived from the Verna cultivar, an old commercial bread wheat Italian variety grown in organic cultivation. Stone-ground (semi-integral) flour was used for the bread production. This bread was obtained by acid-dough rising for 4–5 hours. The chemical composition of Verna flour—in particular, total proteins (CHN elementary analysis), lipids (Soxhlet method), total polyphenols (high-performance liquid chromatography), and total flavonoids (colorimetric method)—was detected and compared with those of new varieties (six) of bread wheat (Table 1). Concentrations of the principal mineral elements zinc, iron, copper, magnesium, calcium, potassium, phosphorus, manganese, and sodium in the grain digests were determined by inductively coupled plasma-atomic emission spectrometry (Table 2). The semi-integral Verna flour was characterized by a total protein, polyphenol, and flavonoid content superior to the new varieties' content (Table 1). Moreover, the content of mineral elements—in particular, copper, iron, magnesium, phosphorus, and zinc, which are essential for human diet—is significantly higher in the Verna flour variety in comparison to the new ones (Table 2).

Table 1.

Mean Data Relative to Technological, Qualitative, and Functional Characteristics of Soft Wheat

Varietal of wheat	Total proteins (%)	Lipids (%)	Polyphenols (mg/100 g)	Flavonoids (μM/g)
Verna	15.95 ± 2.47	1.60	184.59 ± 76.83	1.80 ± 0.34
New^a	14.52 ± 1.74	2.33	151.80 ± 44.36	1.29 ± 0.20

Data are mean ± SD values.

Bilancia, Bolero, Eureka, Mieti, Nobel, and Palesio.

Table 2.

Mineral Element Content in the Grain of Verna and New Soft Wheat Varieties

	Mineral contents (mg/kg)
Varietal of wheat	Ca	Cu	Fe	K	Mg	Mn	Na	P	Zn
Verna	348.77 ± 26.91	5.89 ± 0.41	39.55 ± 2.81	5,165.67 ± 191.84	1,333.00 ± 45.55	30.05 ± 2.06	14.67 ± 2.66	4,586.33 ± 153.06	51.33 ± 3.64
New^a	501.57 ± 19.03	5.57 ± 0.29	36.10 ± 1.99	5,197.72 ± 135.65	1,172.94 ± 32.20	31.24 ± 1.46	16.18 ± 1.88	3,928.22 ± 108.23	37.66 ± 2.58

Data are mean ± SD values.

Bilancia, Bolero, Eureka, Mieti, Nobel, and Palesio.

Study design

The study was a nonblinded, crossover dietary intervention study with treatments of two 10-week periods interrupted by a 10-week washout period. Before starting, a run-in period for all the subjects was performed. After this period, participants were individually instructed to undertake a 10-week study period (intervention period) with the test bread at about 150 g/day. Subjects were encouraged to adhere to their habitual daily diet and to include such a fixed amount of bread in their daily dietary pattern. The amount of bread to be consumed was provided three times per week to each participant, in weighed portion size, at no cost. After the intervention period, a washout period of 10 weeks was followed by all the subjects (washout period). Subsequently, for the next 10 weeks (control period), a commercially available bread of the same quantity and characteristics of the test bread was given to all the subjects. This commercial bread is obtained with flour derived from a mixture of new commercial varieties, of which the most used are Bilancia, Bolero, Eureka, Mieti, Nobel, and Palesio.

Fasting blood samples were obtained at the beginning and at the end of each period.

Blood measurements

Venous blood samples anticoagulated with 0.129 M sodium citrate (volume ratio 9:1) were collected from the antecubital vein into evacuated plastic tubes (Vacutainer^®, BD, Franklin Lakes, NJ, USA), after an overnight fasting. Whole venous blood was also collected in tubes without anticoagulant. Citrated and serum samples were centrifuged at 2,000 g for 10 minutes at 4°C, and supernatants were stored in aliquots at −80°C until assays. Lipid variables were assessed by conventional methods. Interleukin (IL)-6, IL-8, IL-10, IL-12, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) levels were determined by using the Bio-Plex cytokine assay (Bio-Rad Laboratories, Hercules, CA, USA), according to the manufacturer's instructions.

With regard to hemorheological variables, whole blood viscosity (WBV) and plasma viscosity (PLV) were measured using an LS 30 rotational viscosimeter (Contraves, Zurich, Switzerland), whereas erythrocyte filtration was measured by a model MF4 microcomputer-assisted filtrometer (Myrenne GmbH, Roetgen, Germany). The erythrocyte deformability index was estimated by a curve indicating erythrocyte filtration throughout a 10-minute recording in order to determine rheological properties of erythrocytes, passing them through polycarbonate filters with 5-μm micropores (Nucleopore, Pleasanton, CA, USA). The initial flow rate from the microcomputer-generated curves was used for assessing the erythrocyte deformability index. WBV was analyzed at shear rates of 0.512 second⁻¹ and 94.5 second⁻¹.

Statistical analysis

Statistical analysis was performed by using SPSS (Statistical Package for Social Sciences Inc., Chicago, IL, USA) software for Windows (version 13.0). Results are expressed either as mean ± SD or as median and range, as appropriate. The analyses were simplified by calculating the absolute change for each variable tested (mean value at baseline subtracted from the mean value after intervention for each subject) with independent t sample tests. No carryover effect was observed. Therefore, all data were treated as paired samples from a crossover study. Data that were not normally distributed were logarithmically transformed or analyzed by the nonparametric Wilcoxon signed-ranked test. Data were analyzed by using paired t tests for significant differences between changes observed during test and control intervention periods. Moreover, in order to compare the effect of test bread versus baseline and versus the placebo bread, a general linear model for repeated measurements, after adjustment for age and gender, was performed. A Bonferroni adjustment for multiple comparisons was also performed. A value of P < .05 was considered to indicate statistical significance.

Results

Baseline and demographic characteristics of the subjects enrolled in the study are shown in Table 3. The median age of the studied population was 39.5 years (range, 21–61 years). Five subjects were current smokers. No significant differences for age, BMI, smoking habit, and family history of cardiovascular diseases were observed between men and women.

Table 3.

Demographic and Baseline Characteristics

	Men (n = 11)	Women (n = 9)	P
Age (years)^a	39 (21–59)	45 (27–61)	.6
BMI (kg/m²)^b	26.1 ± 2.5	24.8 ± 4.9	.4
Smoking habit [n (%)]	3 (27.3)	2 (22.2)	.8
Positive family history of CVD [n (%)]	2 (18.2)	1 (11.1)	.7

CVD, cardiovascular disease.

Median (range).

Mean ± SD.

In order to evaluate the possible effects of dietary interventions on the parameters investigated, we performed a general linear model for repeated measurements, after adjustment for age, gender, and BMI change. Table 4 shows adjusted mean values of lipid, inflammatory, and hemorheological parameters before and after dietary interventions with test and control breads. No significant changes for blood pressure and BMI were observed in either period.

Table 4.

Circulating Values of Lipid, Inflammatory, and Hemorheological Variables According to Dietary Interventions

	Test period		Control period		Change (pre-/post-intervention)
	Pre	Post	Pre	Post	Test period	Control period	P value ^a
Lipid variables
Total cholesterol (mg/dL)	211.2 ± 10.8	196.5 ± 9.8^*	202.1 ± 9.5	204.5 ± 9.6	−15.7 (−30.9; 1.7)	2.4 (−4.4; 9.3)	.01
LDL-cholesterol (mg/dL)	137.5 ± 8.1	119.5 ± 7.5^*	133.2 ± 8.5	135.7 ± 8.4	−18 (−30.2; − 5.9)	2.5 (−2.9; 8.1)	.001
HDL-cholesterol (mg/dL)	48.9 ± 2.7	47.3 ± 2.3	48.9 ± 2.7	46.5 ± 2.3^*	−1.6 (−4.1; 0.8)	−2.4 (−4.6; − 0.09)	.4
Triglycerides (mg/dL)	137.1 ± 22.1	150.4 ± 20.6	133.5 ± 16.5	146.1 ± 23.7	13.4 (−17.9; 44.7)	12.6 (−10.5; 35.7)	.6
Inflammatory variables
VEGF (pg/mL)	1,008.1 ± 167.9	960 ± 158.9	1,172.4 ± 302.7	1,024 ± 189.9	−48.1 (−257.7; 161.5)	−148.2 (−551.8; 255.3)	.1
IL-12 (pg/mL)	18.5 ± 6.3	14.4 ± 4.4	16.6 ± 5.8	23.7 ± 7.2	−4.1 (−10.1; 1.9)	−7.1 (1.7–12.4)	.4
IL-1ra (pg/mL)	522.9 ± 74.8	435 ± 75.2	1,198.9 ± 203.8	1,072.5 ± 261.8	−87.9 (−252.5; 76.8)	−126.3 (−830.7; 577.9)	.4
IL-10 (pg/mL)	12.7 ± 1.2	7.4 ± 0.8	15.1 ± 8	8 ± 1.8	−5.3 (−11.3; 0.7)	−7.1 (−14.7; 0.5)	.9
IL-6 (pg/mL)	8.1 ± 1.2	8.7 ± 3.1	6.3 ± 1.2	9.8 ± 5.3	0.6 (−4.9; 6.2)	3.4 (−8.4; 15.3)	.7
IL-8 (pg/mL)	67.4 ± 10.7	43.9 ± 4.1	54.4 ± 4.9	58.4 ± 5.8	−23.5 (−45.3; − 1.5)	4 (−12.4; 20.3)	.02
Hemorheological variables
WBV (mPa · s)
94.500 second⁻¹	4.36 ± 0.03	4.32 ± 0.03^*	4.38 ± 0.07	4.48 ± 0.01	−0.04 (−0.07; 0.001)	0.1 (0.01–0.39)	.02
0.512 second⁻¹	26.1 ± 0.4	24.8 ± 0.5^*	22 ± 0.6	22.6 ± 0.8	−1.3 (−2.3; 0.4)	0.6 (−0.8; 2)	.04
EF (%)	8.4 ± 0.7	9.1 ± 0.6	11.4 ± 0.3	10.7 ± 0.6	0.7 (0.3; 1.1)	−0.7 (1.8; 0.5)	.02
PLV (%)	1.35 ± 0.02	1.34 ± 0.02	1.32 ± 0.02	1.42 ± 0.03	−0.01 (0.01; 0.35)	0.1 (0.03; 0.18)	.03

Data are geometric mean ± SD values and were general linear model–adjusted for age, gender, and BMI change.

Comparison between absolute changes induced by the two interventions (Wilcoxon signed-ranks test).

P < .05 for comparison between pre- and post-intervention values.

EF, erythrocyte filtration.

During the intervention period with the test bread significant decreases for total cholesterol and low-density lipoprotein (LDL)-cholesterol, but not for high-density lipoprotein (HDL)-cholesterol and triglycerides, were reported. Indeed, the study participants reported a 7.4% and a 13.1% decrease for total cholesterol and LDL-cholesterol levels during the test period, respectively. Conversely, no significant changes during the intervention period with the control bread were observed.

With regard to the inflammatory pattern, some pro- and anti-inflammatory cytokines were measured in all the study participants. The test period, but not the control period, showed a significant change only for IL-8 levels (–34.9%), whereas no significant modifications for all the other cytokines were observed.

Furthermore, variables related to the rheological characteristics of blood were also investigated according the two different dietary interventions. After adjustment for age, gender, and BMI change WBV at both high and low shear rates significantly improved at the end of the intervention period, whereas no significant changes during the control period were observed. In addition, changes in erythrocytes' filterability during the intervention period were significantly different from those observed during the control period. Correlation analyses performed among changes of parameters observed between pre- and post-intervention were also obtained. Changes of cholesterol and IL-8 levels were significantly and directly correlated (r = 0.61; P = .0001) during the test period, whereas no significant correlation during the control period was observed.

Discussion

In this 10-week crossover feeding trial in clinically healthy subjects we found that consumption of semi-integral bread obtained from the Verna variety, an old variety of Italian bread wheat, is able to improve lipid, inflammatory, and hemorheological profiles. Conversely, consumption of the same duration of commercially available bread did not show such significant effects on the atherosclerotic risk profile of these subjects. This is one of the few articles showing that bread produced from a stone-ground flour obtained from an old grain variety is able produce positive effects on some patterns related to atherosclerotic disease.

The importance and health benefits of whole grain consumption in the prevention of chronic diseases such as neoplastic and cardiovascular diseases have been widely documented.^1,2 However, the attention paid to grain consumption has been little compared to that for other foods such as fruits and vegetables, although nutritional guidelines put grains and grain products at the base of the food guide pyramid to emphasize their importance for optimal health.^3,4 Carbohydrate intake in the Italian population is peculiar, as Italy shows the highest consumption of carbohydrates from refined cereals. The main sources of carbohydrates in the Italian population are bread and various types of pasta, accounting altogether for almost 40% of the total carbohydrate intake.¹³

To date, consumption of grain products with a high content of whole grain flour, milled from all edible components of grains, has been inversely associated with mortality from and incidence of diabetes and ischemic heart disease in several prospective studies.¹⁴ Conversely, intake of refined flour, which consists mainly of the starchy endosperm, was not associated with diabetes and ischemic heart disease risk in these studies. It has been hypothesized that the observed health benefits of whole grain intake may be attributable to the synergistic effects of dietary fiber and micronutrients found in whole grain foods. Indeed, the bran and germ components of whole grains are rich in fiber, vitamins, minerals, and phytoestrogens.

Our study shows a clear beneficial effect of intake of such an old variety of bread wheat on lipids, inflammatory markers, and hemorheological variables over a 10-week period of dietary intervention. To the best of our knowledge, this is the first report of a possible influence of dietary intervention with this variety of bread on hemorheological profile.

Epidemiological studies have shown that increased blood viscosity is associated with several cardiovascular risk factors as well as with both prevalent and incident cardiovascular diseases.^15,16 Mechanisms by which elevations in rheological factors may promote cardiovascular events are different and include increases in blood pressure, shear stress, ischemia, and blood vessel wall interactions. A relevant feature of the rheological flow is the erythrocyte morphology because the deformability of circulating cells greatly influences the rheological properties of the blood, thus playing a key role in maintaining and regulating the microcirculation. Under pathologic conditions, the erythrocyte deformability is altered, thus affecting the rheological environment at the level of the microcirculation. We previously found an influence of dietary habits on hemorheological parameters.¹⁷

In the present study a significant improvement of all the hemorheological parameters after the dietary intervention with the test bread in comparison to the placebo bread was observed, thus improving the deformability of red blood cells and of the rheological characteristics of the blood.

The mechanisms by which such whole grain bread may contribute to health benefits remain to be fully elucidated. It is known that whole grains are a rich source of fiber, minerals (magnesium, potassium, phosphorus, selenium, manganese, zinc, and iron), vitamins (B group and vitamin E), and related antioxidants.¹⁸ These compounds all may have important biological functions so that by themselves, or by interacting with other substances, they could make an important contribution to reduction in cardiovascular risk. In our study, intake of “healthy” bread was inversely associated with circulating levels of inflammatory markers. Although other observational studies of whole grains have not included measures of inflammation, several studies have estimated measures of carbohydrate quality in relation to inflammatory markers.¹⁹

Notably, in our study we found, similar to what was observed in the Framingham Offspring Cohort study,²⁰ a beneficial effect of bread consumption on total and LDL-cholesterol. On the other hand, however, in our study we were not able to observe any influence of the test bread on HDL-cholesterol or triglycerides. These results are in line with some studies^20,21 but in conflict with another study.²² The discrepancies observed can be explained by several factors. First of all, intake of grain products was estimated on the basis of servings and not quantitatively, which makes a comparison of the different results difficult; furthermore, grains consumed in these studies are different from bread consumed in our intervention study, thus likely having a different content of fiber, minerals, and vitamins, with a different effect on triglycerides.

Our study has several main limitations. An important limitation is the restricted sample size of the study. Further and larger studies need to be conducted before drawing any firm conclusion on the effects of such food products on human health. The results of the present study are just a promising basis for evaluating more completely this aspect of clinical nutrition.

Another limitation is the lack of assessment of dietary habits and physical activity in our study population. The possibility that changes in dietary and/or lifestyle habits have significantly affected parameters investigated cannot be excluded, although, before enrollment, all subjects were instructed by physicians and by an expert dietician to maintain their usual lifestyle habits.

Conclusions

Dietary short-term intake of whole grain bread obtained by an old variety seems to impose a favorable status with regard to lower circulating levels of markers of atherosclerosis. Regular consumption of such an old variety of whole grain bread may be useful for reducing the cardiovascular risk burden of the general population.

Footnotes

Acknowledgments

This study was supported by the Italian Ministry of Education MIUR, Fondazione Monte dei Paschi di Siena, and Ente Cassa di Risparmio di Firenze. We wish to thank Mr. Franco Petrini, Mr. Andrea Grifoni, and Mr. Luciano Piazzetti for cultivating the Verna wheat, for milling the kernels, and for making the bread, respectively.

Author Disclosure Statement

No competing financial interests exist.

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