Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: A randomized, double-masked, crossover study

doi:10.1016/j.clnu.2011.01.001

Clinical Nutrition

Volume 30, Issue 4, August 2011, Pages 443-449

https://doi.org/10.1016/j.clnu.2011.01.001 Get rights and content

Summary

Background & aims

Metabolic effects of dietary fat quality in people with type 2 diabetes are not well-understood. The study objective was to evaluate effects of conjugated linoleic acid (CLA) and safflower (SAF) oils on glycemia, blood lipids, and inflammation. The hypothesis we tested is that dietary oils improve glycemia, lipids, and inflammatory markers in a time-dependent way that follows accumulation of linoleic acid and CLA isomers in serum of subjects supplemented with dietary oils.

Methods

Fifty-five post-menopausal, obese women with type 2 diabetes enrolled, and 35 completed this randomized, double-masked crossover study. Treatments were 8 g daily of CLA and SAF for 16 weeks each. We used a multiple testing procedure with pre-determined steps analysis to determine the earliest time that a significant effect was detected.

Results

CLA did not alter measured metabolic parameters. SAF decreased HbA1c (−0.64 ± 0.18%, p = 0.0007) and C-reactive protein (−13.6 ± 8.2 mg/L, p = 0.0472), increased QUICKI (0.0077 ± 0.0035, p = 0.0146) with a minimum time to effect observed 16 weeks after treatment. SAF increased HDL cholesterol (0.12 ± 0.05 mmol/L, p = 0.0228) with the minimum time to detect an effect of SAF at 12 weeks. The minimum time to detect an increase of c9t11-CLA, t10c12-CLA, and linoleic acid in serum of women supplemented CLA or SAF, respectively, was four weeks.

Conclusions

We conclude that 8 g of SAF daily improved glycemia, inflammation, and blood lipids, indicating that small changes in dietary fat quality may augment diabetes treatments to improve risk factors for diabetes-related complications.

Introduction

Obesity is present in 80% or more of type 2 diabetes cases.¹ Because of the known benefits for overweight individuals with type 2 diabetes, weight loss is recommended by the American Diabetes Association for optimal diabetes management.² Weight loss resulting in decreased visceral adipose mass may be particularly beneficial, as excess visceral adipose tissue is more strongly associated with markers of metabolic risk than subcutaneous adipose tissue.³ A modest 5% loss of body weight can improve glycemia, insulin sensitivity, and blood lipids.⁴ Improvement in glycemia decreases risk for diabetes-related micro- and macrovascular complications.⁵

Achieving and maintaining weight loss requires significant lifestyle and behavior modification.⁶ To aid in weight loss, an estimated 33.9% of people trying to lose weight report using non-prescription dietary supplements.⁷ A number of dietary supplements are marketed for weight loss, one of which is conjugated linoleic acid (CLA).

CLA refers to a group of positional and stereoisomers of linoleic acid. CLA is present in small quantities in ruminant meat and dairy products, primarily as the c9t11 isomer. Dietary supplements typically provide substantially higher quantities of CLA than is consumed from foods. Most supplements contain approximately equal amounts of the c9t11 and the t10c12 isomers, with t10c12-CLA being the more important isomer with regard to weight loss.⁸ In a meta-analysis, dietary CLA supplementation was shown to have a modest effect in reducing fat mass in humans.⁹ However, there are few studies specifically reporting the effects of CLA supplementation in people with type 2 diabetes.

In a study in our laboratory, we found that CLA reduced body weight by 1.1% and total adipose mass by 3.2% in obese, post-menopausal women with type 2 diabetes.¹⁰ Despite a significant decrease in both body and adipose masses, the 5% weight loss suggested for improved glycemia was not achieved within the 16 weeks of intervention.

Safflower oil (SAF) was chosen as a comparison treatment to CLA in this study. SAF is available in U.S. grocery stores and is rich in the essential n-6 polyunsaturated fatty acid (PUFA) linoleic acid. Numerous health organizations have recommendations for dietary linoleic acid intake, generally falling within the range of 3–10% of total energy consumption.¹¹ The average daily intake of linoleic acid for women ages 51–70 in the U.S. is 12.6 g, which equates to 5.7% of energy in a 2000-kilocalorie diet.¹²

To our knowledge, SAF had not previously been implicated in body composition changes in humans, but in our study we unexpectedly found a 6.3% decrease in fat mass of the trunk region, and a 1.6% increase in total body lean mass after SAF supplementation.¹⁰

The unexpected outcomes of this study led us to conduct secondary analyses to address the following: 1) the effect of these oils on metabolic parameters specifically related to glycemia, blood lipids, and inflammation; and 2) the time course of metabolic changes and its relationship to the time course of supplemented fatty acid appearance in the serum. The hypotheses were 1) safflower oil, and not CLA, would improve markers of glycemia, blood lipids, and inflammation, and 2) treatment effects would not become apparent until after an increase in supplemented fatty acids was detected in the serum.

Section snippets

Materials and methods

All clinical procedures were conducted at the Clinical Research Center at The Ohio State University Medical Center (Columbus, Ohio). The study was approved by The Ohio State University Institutional Review Board and the Clinical Research Center Advisory Committee. The study was conducted in agreement with the Declaration of Helsinki, and in accordance with International Harmonization/Good Clinical Practice Guidelines.

Markers of glucose tolerance and insulin sensitivity

We had previously found a decrease in fasting glucose with SAF and no effect of CLA when looking at the change from the beginning to the end of the study.¹⁰ To determine the time course of this change, pre-determined steps analysis was employed. This analysis revealed that 16 weeks was the minimum time of supplementation required for SAF to decrease fasting glucose (Fig. 1A).

QUICKI, a surrogate marker of insulin sensitivity, increased with SAF supplementation while CLA had no effect after 16

Discussion

We previously reported that safflower oil supplementation for 16 weeks decreased fat mass in the trunk region, and CLA decreased total body fat mass and body weight.¹⁰ As a result of these findings, in the present study we hypothesized that safflower oil would improve measures of glycemic control, blood lipids and inflammatory markers, and CLA would have no effect on these parameters. Additionally, we hypothesized that any metabolic effects of safflower oil and CLA would become evident after

Statement of authorship

The contribution of each author is as follows: M. Asp oversaw clinical visits, data collection, data analyses, primary writer and author; A. Collene- oversaw clinical visits, data collection, and was a contributing author and editor of final drafts; L. Norris oversaw clinical visits, data collection, and was a contributing author and editor of final drafts; R. Cole conducted fatty acid analyses of serum samples, participated in data collection, data analyses, and was a participating author and

Conflict of interest statement

There are no conflicts of interest declared by any of the authors.

Acknowledgements

The authors would like to thank Yi Liu for her assistance with the statistical analyses, Julia Richardson for editorial assistance with the manuscript, the staff of the Clinical Research Center for their help with data collection, and the study participants for their time and dedication to being a part of the study. This study was funded by an unrestricted gift from Cognis Corporation (Monheim, Germany, and Cincinnati, Ohio), the National Center for Research Resources (UL1RR025755), the

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We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF.
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Among 41,335 participants, 6173 incident cases of AF were ascertained, with median follow-up time of 14 y. In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), circulating n–6 levels were not associated with incident AF. For LA, the hazard ratio per interquintile range was 0.96 (95% confidence interval [CI]: 0.89, 1.04), and for AA, 1.02 (95% CI: 0.94, 1.10), with little evidence of heterogeneity between cohorts. Associations were similarly nonsignificant across subgroups of age, race, and biomarker fraction.
Biomarkers of n–6 fatty acids including LA and AA are not associated with incident AF. These findings suggest that overall effects of n–6 PUFAs on influencing AF development are neutral.
Conjugated linoleic acid (CLA) as a functional food: Is it beneficial or not?
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Conjugated linoleic acid (CLA) has attracted great attention in recent years as a popular class of functional food that is broadly used. It refers to a group of geometric and positional isomers of linoleic acid (LA) with a conjugated double bond. The main natural sources of CLA are dairy products, beef and lamb, whereas only trace amounts occur naturally in plant lipids. CLA has been shown to improve various health issues, having effects on obesity, inflammatory, anti-carcinogenicity, atherogenicity, immunomodulation, and osteosynthesis. Also, compared to studies on humans, many animal researches reveal more positive benefits on health. CLA represents a nutritional avenue to improve lifestyle diseases and metabolic syndrome. Most of these effects are attributed to the two major CLA isomers [conjugated linoleic acid cis-9,trans-11 isomer (c9,t11), and conjugated linoleic acid trans-10,cis-12 isomer (t10,c12)], and their mixture (CLA mix). In contrast, adverse effects of CLA have been also reported, such as glucose homeostasis, insulin resistance, hepatic steatosis and induction of colon carcinogenesis in humans, as well as milk fat inhibition in ruminants, lowering chicken productivity, influencing egg quality and altering growth performance in fish. This review article aims to discuss the health benefits of CLA as a nutraceutical supplement and highlight the possible mechanisms of action that may contribute to its outcome. It also outlines the feasible adverse effects of CLA besides summarizing the recent peer-reviewed publications on CLA to ensure its efficacy and safety for proper application in humans.
Safflower (Carthamus tinctorius L.) oil could improve abdominal obesity, blood pressure, and insulin resistance in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled clinical trial
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The results of that study revealed that the minimum time required to reduce Hemoglobin A1c (HbA1c), C-Reactive Protein (CRP), inflammatory factors, and insulin resistance was 16 weeks. To achieve a significant increase in serum HDL-C and adiponectin, the duration of intervention had to be at least 12 weeks, as well (Asp et al., 2011). Regarding the growing prevalence of MetS as a chronic disease worldwide along with its cardiovascular complications as well as limited and contradictory studies on the effects of safflower seed oil, the current trial aims to evaluate its pharmacological effects on cardiovascular risk factors in patients with MetS.
Carthamus tinctorius L. (Safflower) has been widely recommended to treat metabolic disorders in traditional herbal medicine in Persia, China, Korea, Japan, and other East-Asian countries. The anti-hypercholesterolemic and antioxidant effects of this plant have been well documented, but its protective effects against Metabolic Syndrome (MetS) have not been fully illustrated.
The present study aimed to evaluate the effects of safflower oil on MetS risk factors.
In this randomized, double-blind, placebo-controlled clinical trial, 67 patients with MetS were administered either divided 8 g safflower oil or placebo daily for 12 weeks. All patients were advised to follow their previous diets and physical activities.
Safflower oil resulted in a significant reduction in waist circumference (-2.42 ± 3.24 vs. 0.97 ± 2.53, p<0.001), systolic blood pressure (-8.80 ± 9.77 vs. -2.26 ± 8.56, p = 0.021), diastolic blood pressure (-3.53 ± 7.52 vs. -0.70 ± 6.21, p = 0.041), fasting blood sugar (-5.03 ± 10.62 vs. 2.94 ± 7.57, p = 0.003), and insulin resistance (-0.59 ± 1.43 vs. 0.50 ± 1, p = 0.012), but an increase in adiponectin level (0.38 ± 0.99 vs. -0.09 ± 0.81, p = 0.042) in the treatment group in comparison to the placebo group. The results revealed a direct relationship between leptin level and Body Mass Index (BMI) in both groups (p<0.001). In addition, increase in BMI resulted in a non-significant decrease in adiponectin level in both groups. Moreover, no significant difference was observed between the two groups regarding lipid profiles, leptin serum level, serum creatinine concentration, and other outcomes.
Safflower oil without lifestyle modification improved abdominal obesity, blood pressure, and insulin resistance in patients with MetS.
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Safflower like many other medicinal plants, is an available herbal remedy with low side effects and costs. The oil and extract of its seed have been used traditionally to treat metabolic syndrome and obesity (Nimrouzi et al., 2020b; Asp et al., 2011; Moon et al., 2001; Kang et al., 1999). The anti-hypercholesterolemic, anti-inflammatory and antioxidative effects of this plant and its role on fatty acid oxidation and homeostasis of trace elements have been well documented, as well (Koyama et al., 2006; Neschen et al., 2002; Moon et al., 2001; Kang et al., 1999).
Diabetes mellitus (DM), as a multiorgan syndrome, is an endocrine and metabolic disorder that is associated with male reproductive system dysfunction and infertility. Safflower (Carthamus tinctorius L.) as an herbal remedy improves DM and infertility-related disorders. The anti-hypercholesterolemic, anti-inflammatory, and antioxidative properties of this herb have been well documented, but its role in testosterone production, male reproductive system and zinc homeostasis has not been fully illustrated.
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After the intervention, the activity of antioxidant enzymes and the level of testosterone and gonadotropins significantly decreased in the rats with DM in comparison to the others. However, lipid peroxidation and serum level of insulin, leptin and TNF-α increased and the testicular level of zinc significantly changed in the rats with DM compared to the control groups (p < 0.05). The gene expression of NF-κB and TNF-α were also significantly increased and the gene expression of Nrf2, StAR, P450scc and 17βHSD3 were decreased in the testis of diabetic rats (p < 0.05). The results showed that pretreatment and treatment with safflower seed oil could improve these parameters in diabetic rats compared with untreated diabetic rats (p < 0.05).
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Influences of dietary oils and fats, and the accompanied minor content of components on the gut microbiota and gut inflammation: A review
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CLAs supplementation could also exert prebiotic actions on both Bacteroidetes/Prevotella ratio and Akkermansia muciniphila abundance, and showing positive effects in inducing the expression of genes encoding gastric proteins, which was related with regulation of energy homeostasis (Chaplin, Parra, Serra, & Palou, 2015). Results from the clinical studies also reported the positive effects of the CLAs supplementation for modulating the gut microbiota profiles, inflammation response and the overall lipid metabolism conditions (Asp et al., 2011; Bassaganya-Riera et al., 2012; Farnworth et al., 2007). As have mentioned, the different dietary oils and fats contain different fatty acids varying in degree of saturation or acyl chain length.
The processing of dietary lipids in the intestinal lumen involves metabolic processes of the host and also of the microbial organisms that reside in the gut. Whereas, in the edible oil, there are also other minor content of components, such as fat-soluble micronutrients. The dietary oils and fats, as well as these accompanied components have different effects on the gut microbiota structure, which is also closely associated with gut inflammation, and the host health.
This review of the literature highlights the effects of dietary oils and fats, as well as the minor content of accompanied components on the gut microbiota, and the gut inflammation, with special respect to illustrating the roles of high fat diet (HFD), fatty acid composition, the n6/n3 poly-unsaturated fatty acid (PUFA) ratio, the conjugated linoleic acids (CLAs), the fatty acid chain length and triacylglycerol (TAG) structure, the fat-soluble micronutrients, and some other minor content of components, such as trans-fatty acids (TFAs). The interactions between the dietary oils and fats and gut microbiota are also briefly discussed.
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2020, Cold Pressed Oils: Green Technology, Bioactive Compounds, Functionality, and Applications
Safflower seed is an important alternative oil crop because of its high oil content (27%–32%), which is rich in linoleic acid (55%–70%). Cold pressed safflower oil possesses high nutritional and pharmaceutical values due to its noticeable amounts of bioactive compounds and essential fatty acids. The oil is known as a valuable source of α-tocopherol, which shows the highest vitamin E activity, and it therefore has many health benefits such as prevention and treatment of hyperlipemia, arteriosclerosis, and coronary heart disease. Safflower seed is suitable for growing all over the world, with high soil and climate adaptation. The most common volatile compounds found in cold pressed safflower oil are paeonol, α-asarone, β-asarone, 1-methyl-4-(2-propenyl)-benzene, diethenyl-benzene, acetoin, methyl benzene, hexanal, p-xylene, heptanal, and 2-octenal. This chapter reviews the extraction techniques of safflower seed oil, bioactive compounds in cold pressed safflower oil and their health effects, aroma compounds found in cold pressed safflower oil, application areas, adulteration, and some process contaminants such as polycyclic aromatic hydrocarbons (PAHs) and 3-monochloropropanediol (3-MCPD) esters.

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Original ArticleTime-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: A randomized, double-masked, crossover study

Summary

Background & aims

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Markers of glucose tolerance and insulin sensitivity

Discussion

Statement of authorship

Conflict of interest statement

Acknowledgements

Lancet

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Am Heart J

Prevention Conference VII: obesity, a worldwide epidemic related to heart disease and stroke: group III: worldwide comorbidities of obesity

Circulation

Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association

Diabetes Care

Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study

Circulation

Weight management through lifestyle modification for the prevention and management of type 2 Diabetes: rationale and strategies: a statement of the American diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition

Diabetes Care

Use of dietary supplements for weight loss in the United States: results of a national survey

Obes (Silver Spring)

Original Article
Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: A randomized, double-masked, crossover study