The effects of canola and olive oils on insulin resistance, inflammation and oxidative stress in women with type 2 diabetes: a randomized and controlled trial

Abstract

Background

A number of studies have shown that consumption of vegetable oils may improve diabetes complications including inflammatory response and oxidative stress, but no study has been done on the effects of canola oil (CO) and olive oil (OO) consumption in patients with type 2 diabetes. This clinical trial was done to compare the effects of CO and OO on insulin resistance, inflammation and oxidative stress in women with type 2 diabetes.

Methods

This randomized controlled clinical trial was done on 77 type 2 diabetic women. 4 weeks before the intervention, lipid-lowering drugs intakes were cut under the supervision of an endocrinologist. The participants were randomly divided into 2 intervention groups (Balanced diet +30 g/day CO or OO) and one control group (Balanced diet +30 g/day of sunflower oil (SFO)). Dietary intakes were assessed using three 24-h food records at baseline and at weeks 4 and 8 of the interventions. At baseline and after 8 weeks, height, weight, waist circumference, fasting blood sugar (FBS), serum insulin, C-reactive protein (CRP) and malondialdehyde (MDA) were measured.

Results

After the intervention in the inter-group analysis, CRP level was reduced significantly in CO and OO groups but no significant changes were observed in other factors. CRP reductions were also significant between all of the groups but not for other factors.

Conclusions

Replacing CO and OO with SFO as part of daily dietary fat in the diet of people with type 2 diabetes is recommended for reducing Inflammation and Oxidative Stress.

Trial registration.

This study is approved by the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1394.27) and is recorded in the Iranian Registry of Clinical Trials (IRCT2015062722818N1).

Introduction

Prevalence of diabetes mellitus is one of the most challenging and serious health problems in the twenty-first century. The number of people with diabetes is growing more than expected [1].

Insulin resistance plays a major role in the pathogenesis of type 2 diabetes [2]. Previous studies have shown that diets with saturated fatty acids interfere with insulin action [3]. A number of cross-sectional studies have shown that insulin resistance and type 2 diabetes are related with high level of CRP [4]. In addition, it seems that insulin resistance and oxidative stress play important roles in the pathology of type 2 diabetes [5–7].

Oxidative stress can be a pathophysiological link between cardiovascular diseases (CVD) and diabetes [8]. Studies have shown that oxidative stress by reactive oxygen species (ROS) and nitrogen species produced during hyperglycemia have an important role in diabetic damages in different organs [9]. During the diabetes disease, free and active radicals are produced. Increased free radical and reduced antioxidant defense mechanisms damage cellular organelles and enzymes, which lead to the increase of lipid peroxidation and insulin resistance, damage and finally death of beta cells in diabetic patients [10]. Studies have shown that the changes in dietary fatty acids can play an important role in the prevention and treatment of coronary heart disease [11], and inflammatory responses [12].

CO and OO are good sources of monounsaturated fatty acid (MUFA) [13]. CO contains 11% omega-3 polyunsaturated fatty acids (PUFA), 53–59% MUFA, 22% omega-6 PUFAs and 7.1% saturated fatty acids (SFA) [14–16], and its ratio of omega-6 to omega-3 is appropriate [16, 17]. OO contains 1% omega-3 PUFAs, 73.3% oleic acid (a MUFA), 7.9% omega-6 PUFAs and 13.5% SFA [17]. OO phenolic compounds like tyrosol, oleuropein aglycone, hydroxytyrosol and their derivatives have a high antioxidant capacities [18].

By lowering cholesterol level and stimulation of anti-inflammatory effects, high PUFA and alpha-Linolenic acid (ALA) diets have particularly protective effects on the heart [8]. Several studies have reported that CRP level is inversely related with EPA and DHA [8, 19]. The antioxidant activity of oils depends on vitamin E and Phytochemicals value and fatty acid’ compositions and OO consumptions has a protective effect against Oxidative Stress [20–22].

Due to the effects of fatty acids’ composition of diet on insulin resistance, inflammation and oxidative stress and developing of diabetes and CVD, this study was aimed to compare the effects of CO and OO with SFO, which is the most common oil being consumed in Iran, in patients with type 2 diabetes.

Methods

Patients

This study was held from July 2015 to November 2015. 81 females over 50 years old with type 2 diabetes and an average body mass index (BMI) of 28 kg/m² were recruited. Participants were selected from Motahhari clinic in Shiraz, according to these inclusion criteria:

Female gender, records of type 2 diabetes of at least 6 months, and the routine use of SFO. Patients who need insulin and/or lipid-lowering drugs; patients with thyroid disorders, kidney and liver diseases, CVD; participating in other studies in the past 6 months; taking non-steroidal immunosuppressant, cyclosporine and warfarin; smokers, alcohol consumers. People who have triglycerides (TG) > 400 (mg/dL) and/or low-density lipoprotein cholesterol (LDL-C) > 200 (mg/dL) were not included in the study.

Study design

This study was in a single-centered, parallel group, and randomized controlled clinical trial. It was approved by the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1394.27) and was recorded in the Iranian Registry of Clinical Trials.

All study protocols were introduced to the patients and then the written consents were taken. The sample size was estimated based on a previous study by POWER SSC software [23] and with considering the mean difference between independent groups by assuming the probability of Type I error (α) equal to 0.05, the power of (β-1) equal to 80%, the mean difference (μ1-μ2) equal to 0.35 and standard deviation (σ) equal to 0.40. After adding 25% drop out rate, 25 persons waere considered in every group.

Four weeks before the intervention, intakes of lipid-lowering drugs were discontinued under the supervision of an endocrinologist. Then, by using balanced block method, patients were randomly divided into 3 groups.

Weight maintenance (55% carbohydrate, 18% protein and 27% fat) diet was designated for each participant by Estimated Energy Requirement (EER) equation, each diet contained 30 g per day of vegetable oils (SFO, CO and OO) and patients were asked to add it to their salads or their boiled foods by using a small measuring cup. Fatty acids’ compositions of consumed oils are extracted in Shiraz Azmoon Gostar laboratory and they are shown in Table 1.

Table 1.

Fatty acids composition of consumed oils

Fatty acids	Olive oil	Canola oil	Sunflower oil
C16	11.2	6.5	7.8
C18	2.9	2.5	4.9
C20	0	0.2	0.4
C22	0	0	0.9
C18:1	72.5	59.4	27.6
C18:2	11	21.3	58
C18:3	1	9.9	0
C20:1	0	0.2	0.4
SFA∑	14.1	9.2	14
MUFA∑	72.5	59.6	28
PUFA∑	12	31.2	58

All values are % of total fatty acids, SFA: Saturated fatty acid,

MUFA Monounsaturated fatty acid, PUFA Polyunsaturated fatty acid

Anthropometric measurements and assessment of dietary intake

At the baseline and at the end of the intervention, anthropometric indices, including height, weight, and waist circumference were measured.

Patients’ weights were measured in light clothes, and without shoes with an accuracy of 100 g by a digital balance (BF11 OMRON made in France). Height was measured with an accuracy of 0.5 cm by a non-stretchable tape measure. Then, BMI was calculated as Weight (kg)/ (Height (m)* Height (m)).

At baseline, week 4 and week 8 of the intervention, 3 days 24-h record and physical activity record were filled by participants. Participants were asked not to change the recommended diet, medications and daily physical activity during the intervention.

Biochemical evaluation of blood

Five milliliters of blood samples were taken after 12 to 14 h fasting from all patients and were held for 15 to 20 min at room temperature, and then, they were centrifuged for 5 min at 300 rpm. Serums were kept on −76 °C for further analyses. MDA level was measured by spectrophotometry, serum insulin and CRP were measured by ELISA (IBL kit), and insulin resistance was calculated by the following formula:

$$\mathit{\text{HOMA}}-\mathit{IR}=\frac{\mathit{\text{Glucose}}\left(\frac{\mathit{mg}}{\mathit{dl}}\right)\times \mathit{\text{Insulin}}\left(\frac{\mathit{\mu U}}{\mathit{ml}}\right)}{405}$$ 1

Statistical analysis

24-h food records were analyzed by Nutritionist IV software. Data were analyzed by SPSS 19. P values less than 0.05 were considered significant.

Normal distribution of variables was assessed by using Kolmogorov-Smirnov test. Paired-Samples T-test was used to compare the anthropometric measurements, energy, dietary intakes, CRP, FBS, Insulin and MDA before and after intervention. One-way ANOVA was used to compare the mean changes of CRP, FBS, Insulin, HOMA-IR and MDA among the three groups and then, Post-Hoc test was used for further analyses.

Data availability

Please contact author for data requests.

Result

Out of 81 participants, one in the OO group (not following the dietary regimen), one in the CO group (need of insulin) and two in the SFO group (need for blood lipids lowering drugs) were excluded, and 77 of them completed the study (Fig. 1). Participants reported no side effects associated with the consumption of the oils.

Fig. 1.

Participants flow diagram throughout the study

General characteristics, anthropometric status, and the dietary intake of participants at baseline are shown in Table 2. No significant differences in energy and fatty acid intakes, macronutrient distributions, weights, waist circumferences, BMIs and physical activities were observed in the control and the intervention groups.

Table 2.

General characteristics, anthropometric status, physical activity and dietary intake of participants at baseline

Variables	Olive oil	Canola oil	Sunflower oil	p-Value*
Age (Year)	59 ± 7	58 ± 6	57 ± 5	0.63
Height (cm)	155 ± 5	156 ± 4	155 ± 4	0.67
Weight (kg)	69.8 ± 14	70.7 ± 7.8	68 ± 9.9	0.68
BMI (kg/m2)	28.7 ± 4.8	28.9 ± 3.6	28.1 ± 3.8	0.76
Waist circumference (cm)	95.2 ± 10.5	98.8 ± 6.8	95.6 ± 9.7	0.31
Physical activity (METh/day)	27.7 ± 2	27.5 ± 2	28.6 ± 2.2	0.20
Fat (%Energy)	29.4 ± 3.6	27.7 ± 4.5	28.9 ± 5.4	0.39
Protein (%Energy)	16.8 ± 2.4	17.5 ± 2.9	17 ± 2.1	0.58
Carbohydrate (%Energy)	55.7 ± 5.4	56.1 ± 6.5	55.2 ± 7.1	0.89
Energy (kcal/day)	1586.6 ± 337.3	1642.3 ± 299.0	1542.6 ± 262.4	0.50
Cholesterol (mg/day)	211.2 ± 71.0	206.3 ± 72.1	231.6 ± 83.7	0.46
SFA (% of total energy)	13.6 ± 3.6	13.4 ± 3.1	13.0 ± 4.2	0.85
MUFA (% of total energy)	9.6 ± 3.8	10.0 ± 3.8	12.1 ± 2.6	0.08
PUFA (% of total energy)	22.7 ± 3.9	22.4 ± 8.5	18.3 ± 1.5	0.06
Dietary fiber (% of total energy)	14.9 ± 5.6	18.0 ± 5.8	13.99 ± 3.9	0.07
Soluble fiber (% of total energy)	0.4 ± 0.3	0.4 ± 0.2	0.39 ± 0.3	0.54

BMI body mass index, SFAs saturated fatty acids, MUFAs monounsaturated fatty acids, PUFAs polyunsaturated fatty acids. All values are mean ± Standard deviation. * One way ANOVA

Dietary intakes of participants during the intervention are given in Table 3. No significant differences were observed in energy and fiber intakes, macronutrient distributions and physical activities in the three groups. MUFA and PUFA intakes had significant differences among the three groups (P < 0.01 for both).

Table 3.

Anthropometric status, physical activity and dietary intake of participants during the intervention

Variables	Olive oil	Canola oil	Sunflower oil	p-Value*
Weight (kg)	69.5 ± 14.1	70.7 ± 8	67.8 ± 9.8	0.63
BMI (kg/m2)	28.6 ± 4.9	28.9 ± 3.7	28 ± 3.7	0.71
Waist circumference (cm)	94.9 ± 10.6	98.9 ± 7.3	95.2 ± 9.3	0.23
Physical activity (METh/day)	27.7 ± 2.1	27.6 ± 1.8	28.2 ± 1.9	0.67
Fat (%Energy)	28.3 ± 3.9	27.8 ± 2.9	28 ± 4.5	0.91
Protein (%Energy)	16.8 ± 2.1	16.5 ± 1.4	16.8 ± 1.7	0.82
Carbohydrate (%Energy)	56.9 ± 5.6	57.3 ± 4.2	56.6 ± 5.6	0.89
Energy (kcal/day)	1614.8 ± 267.0	1620.8 ± 252.0	1614.9 ± 316.7	1.00
Cholesterol (mg/day))	197.3 ± 76.4	183.1 ± 49.8	178.5 ± 65.5	0.56
SFA (% of total energy)	13.4 ± 2.9	12.0 ± 2.3	12.9 ± 3.1	0.20
MUFA (% of total energy)	24.57 ± 2.6	21.7 ± 3.0	12.3 ± 2.3	0.00
PUFA (% of total energy)	6.8 ± 2.1	11.3 ± 2.0	19.0 ± 1.4	0.00
Dietary fiber (% of total energy)	18.5 ± 5.5	17.7 ± 4.7	16.3 ± 4.2	0.28
Soluble fiber (% of total energy)	0.5 ± 0.2	0.53 ± 0.2	0.4 ± 0.2	0.28

BMI body mass index, SFAs saturated fatty acids, MUFAs monounsaturated fatty acids, PUFAs polyunsaturated fatty acids. All values are mean ± Standard deviation. * One way ANOVA

Comparisons of the mean changes in FBS, MDA, CRP, Insulin and HOMA-IR levels among the three groups are illustrated in Table 4. There were no significant differences in FBS, insulin and HOMA-IR levels in the three groups. In the inter-group analysis CRP decreased significantly in OO (from 12 to 9.5, P < 0.01) and CO (from 15 to 11.8, P < 0.01) after the intervention. No changes were observed in SFO group. There were significant differences in CRP levels (P = 0.02) among the three groups. Turkey Post Hoc test showed significant reduction of CRP in CO (P = 0.02) in comparison to the SFO group (Table 5).

Table 4.

Comparison of the changes in hematological parameters among the three groups before and after intervention

	Olive Oil			Canola oil			Sunflower oil
	Before	After	Changes	Before	After	Changes	Before	After	Changes
FBS (mg/dL)	135 ± 30.3	134.1 ± 40.3	−0.9	127.85 ± 45.73	128.00 ± 42.83	0.1538	145.44 ± 58.28	141.20 ± 48.55	−4.24
MDA (mg/dL)	5.4 ± 1.5	5 ± 1.4	−0.4	5.21 ± 1.08	4.92 ± 1.13	−0.2869	4.84 ± 1.09	4.69 ± 1.05	−0.14
Insulin (mg/dL)	9.3 ± 8.3	8 ± 6.8	−1.3	8.70 ± 6.07	10.47 ± 6.09	1.7726	8.97 ± 7.69	9.55 ± 5.95	0.58
Homa-IR	3.3 ± 3.6	2.7 ± 2.7	−0.6	2.57 ± 1.79	3.13 ± 1.78	0.5564	3.41 ± 4.29	3.11 ± 1.82	−0.30
CRP (mg/dL)	12 ± 3.8	9.5 ± 2.8	−2.5	15.05 ± 6.28	11.77 ± 3.67	−3.2779	11.06 ± 4.35	10.74 ± 3.50	−0.32

FBS fast blood sugar, MDA malondialdehyde, CRP C-reactive Protein

Table 5.

Significant value of changes in hematological parameters among the three groups before and after intervention

	Inter-group analysis P-Valuea			Intra-group analysis P-Valueb
	Olive oil	Canola oil	Sunflower oil	Between groups
FBS (mg/dL)	0.88	0.98	0.56	0.92
MDA (mg/dL)	0.13	0.23	0.51	0.89
Insulin (mg/dL)	0.35	0.14	0.74	c0.10
Homa-IR	0.36	0.13	0.73	c*0.05
CRP (mg/dL)	*0.001	*0.003	0.47	0.02

^aThe value of paired-samples t-test, ^bThe value of ANOVA test, ^cNonparametric test value, ^*significant changes

FBS fast blood sugar, MDA malondialdehyde, CRP C-reactive Protein

Discussion

The results of our study showed that there were no significant differences among the effects of OO, CO and SFO consumption on MDA in women with diabetes. These changes were also not significant in each group. Based on previous studies, the effects of different kinds of oils on MDA are controversial and they are as follow.

OO with high content of MUFA, low content of PUFA and also with antioxidants like polyphenol and tocopherol causes strong protective effects against Oxidative Stress [20–22]. Positive results for CO consumption are also reported in some studies while this effect did not observe with SFO consumption in which MUFA content is lower and PUFA content is higher with respect to CO and OO (Table 1). [24].

It is shown that omega-3 fatty acids reduce oxidative stress in fat mass [3], and also, Ebrahimi et al. have reported that MUFA-enriched diet increased the resistance to oxidative damage compared to PUFA (omega-6 type) [24]. In regard to other study results on MDA, it seems that CO and OO consumptions have positive effects on oxidative stress, but it seems that the short period of the intervention in this study causes non-significant results.

We found no significant variations in the effects of OO, CO and SFO consumption on FBS and insulin resistance in women with type 2 diabetes. Also, no significant improvement was seen in glycemic status in each group.

On previous studies, controversial results were derived. In the Nigam study, consumption of 20 g OO, CO or SFO for 6 months showed significant reductions in fasting insulin and HOMA-IR in OO group. Results of other studies indicated that CO and OO have positive effects on insulin resistance [25, 26]. MUFs reduce insulin resistance by the oxidation of fatty acids which causes the activation and proliferation of alpha receptor. This leads to the reductions in activation of sterol regularity element-binding proteins and lipogenesis inhibition [25]. OO with high content of MUFA and PUFA may stimulate insulin secretion from beta cells [27]. In Gillingham study, SFA substitution with MUFA led to modulation of insulin sensitivity and glycemic control [28]. Lotfi and Zhao showed that MUFA in CO and OO compared to SFA, may improve glucose intolerance and insulin resistance but there were no significant differences on the peripheral insulin sensitivity [19, 29]. In Soaser study, significant increases in insulin, insulin resistance and FBS were observed [30].

In this study a significant reduction of CRP was found in CO in regard to SFO. Based on previous studies with dietary enrichments in omega-3 such as CO, ALA with high content PUFA diet, fish oil with weight loss diet, and Mediterranean diet, significant reductions of CRP were observed [19, 31–33], while opposite results were also reported [3, 8, 24]. But, no study has been done on the efficiency of CO and OO on the CRP of patients with type 2 diabetes. It seems that the causes and mechanisms of reducing CRP by compounds in CO and OO are as follow:

ALA and omega-3 content of CO and OO have anti-inflammatory effects. By formation of prostaglandin I3, ALA prevents formation of thromboxane A2 which decreases cardiovascular risks [24]. Omega-3 fatty acids in OO inhibit the inflammation process of omega-6 fatty acids and decrease concentrations of arachidonic acid [34]. Anti-inflammatory effects of omega-3 are shown by reducing the formation of leukocytes [8]. Also, OO has phenolic compounds which are anti-inflammatory [35].

Conclusion

Prevalence of diabetes mellitus is one of the most challenging and serious health problems and the consumption of vegetable oils may improve diabetes complications. In this study, a clinical trial considered the effects of CO and OO on insulin resistance, inflammation and oxidative stress in women with type 2 diabetes. Limitations include short duration of intervention and dietary examination based on individual reports. The strengths part include cutting lipid lowering drugs to demonstrate the effect of diet on health improvement, gender, age, menopause and hormonal status of participants.

After the intervention in the inter-group analysis, results show that CRP levels were reduced significantly in CO and OO groups but no significant changes were observed in other factors. CRP reductions were also significant between all of the groups but not for other factors. Replacing CO and OO with sunflower oil as part of daily dietary fat in the diet of people with type 2 diabetes is recommended to reduce Inflammation and Oxidative Stress. In future studies it is recommended to increase the number of samples, to study with different intervention periods, to study on hypertension or lipid abnormalities.

Abbreviations

ALA

Alpha-Linolenic Acid

BMI

Body Mass Index

CO

Canola Oil

CRP

C - reactive protein

CVD

Cardiovascular Diseases

EER

Estimated Energy Requirement

FBS

Fasting Blood Sugar

LDL-C

Low-density Lipoprotein Cholesterol

MDA

Malondialdehyde

MUFA

Monounsaturated Fatty Acid

OO

Olive Oil

PUFA

Polyunsaturated Fatty Acid

ROS

Reactive Oxygen Species

SFA

Saturated Fatty Acid

SFO

Sunflower Oil

TG

Triglycerides

Authors’ contributions

Masoumeh Atefi carried out the all protocols described in the manuscript and wrote it too. Gholam Reza Pishdad list the probable patients for the study and cut lipid-lowering drug of selected patients. Shiva Faghih participated in the design of the study and verified the study and edit the manuscript.

Funding

This article was extracted from an MSc thesis written by Masoumeh Atefi which was funded by Shiraz University of Medical Sciences with the grant number of “94–7493”.

Ethics approval and consent to participate

This study is approved by the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1394.27) and is recorded in the Iranian Registry of Clinical Trials (IRCT2015062722818N1).

Competing interests

The authors declare that they have no competing interests.