Effects of 12 weeks Treatment with Conjugated Linoleic acid Supplementation on Body Fat Mass and Lipid Metabolism in Healthy, Obese Individuals - A Pilot Study

 

B. Lalitha Devi¹, N.S. Muthiah², K. Satya Narayana Murty³, Sanjay Kumar⁴

¹Research Scholar, Bharath University, Associate Professor of Pharmacology GSL Medical College Rajamahendravaram-533296 (AP)

²HOD & Professor of Pharmacology, Sri Balaji Medical College, Chrompet, Chennai-600044 (Tamilnadu)

³HOD & Professor of Pharmacology GSL Medical College, Rajamahendravaram-533296 (AP)

⁴Professor of Pharmacology GSL Medical College, Rajamahendravaram-533296 (AP)

 

ABSTRACT:

Background: obesity is a condition characterized by accumulation of excess body fat and associated with risk for developing cardiovascular disease and diabetes. Therefore, management of obesity and body weight are increasingly considered an important approach for maintaining healthy cholesterol profiles and reducing cardiovascular risk which endangers the life of an individual.

Objectives: The objective is to study the effects of Conjugated linoleic acid in reducing body fat mass and lipid profile, to estimate HS-CRP and to observe the adverse effects during the study period.

Methodology: This is a pilot study and   is a hospital based prospective, interventional, open, non-randomized clinical study. In the study group, 22 patients are included who fulfill the inclusion criteria. Baseline values of lipid profile and HS- CRP are recorded  and body fat measurement  done with the help of Omron Karada scan at baseline and at the end of three months treatment. Anthropometric measurements are also noted at baseline and at the end of three months. Lipid profile and HS-CRP noted again at the end of the study.

Results: The pilot study was conducted for a period of 3 months from 20-10-2016 up to 20-1-2017. Initially 22 patients were enrolled for the study and there are 2 dropouts after 1 month of initiation of the study. In the remaining 20 subjects weight reduction of 5-8 % was observed in 12 patients. In 2 patients there is reduction in skin fold thickness and in one patient fat percentage reduced though there is no much reduction of weight. In 5 subjects there is no change in body weight, fat percentage or skin fold thickness. No adverse events observed in any of the subjects.

Interpretation and conclusion: From the above results it was observed that there is weight reduction with Conjugated linoleic acid, the test drug as well as reduction of body fat and skin fold thickness. There are no adverse events observed. The above findings are to be verified in the full scale study  and after that it can be concluded that the drug might be useful in the treatment of diet induced obesity.

 

 

 

 

INTRODUCTION:

Obesity is a condition characterized by accumulation of excess body fat and is a chronic health threatening disease. Its incidence is high, but only a small percentage of patients are treated with anti-obesity drugs. The potential of pharmacotherapy for obesity is enormous, though there are some limiting factors.

 

WHO classification of obesity based on BMI:

Grade I overweight (commonly and simply called overweight): BMI of 25-29.9 Kg/ m2 Grade II overweight (commonly called obesity): BMI of 30-39.9 Kg/m2 Grade III overweight (commonly called severe or morbid obesity): BMI greater than or equal to 40 Kg/m2 The cut-off for each grade varies according to an individual’s ethnic background.

 

Conjugated linoleic acid in the treatment of obesity:

An ideal anti obesity drug should be efficacious, safe and produces sustained weight reduction leading to the improvement in the cardio metabolic biomarkers, and thus reducing the incidence of obesity associated co-morbidities.

 

Conjugated linoleic acid (CLA) is a mixture of different types of isomers of linoleic acid, primarily position and geometric isomers which are conjugated dienoic derivatives of linoleic acid. CLA is found preferentially in dairy products and meat.¹ CLA is an omega-6 fatty acid important to human health. The major dietary source of CLA for humans is ruminant meats such as beef, lamb and dairy products including milk and cheese.^2,3 Animal studies have promising effects of CLA on reduction of body weight and fat deposition. The majority of animal studies have been conducted using CLA mixtures that contained approximately equal amounts of trans-10 cis-12 (t10c12) and cis 9 trans-11 isomers (c9t11). The double bonds of CLA are conjugated and separated by a single bond between them. CLA is marketed in dietary supplement form or as a NEUTRACEUTICAL. Neutraceuticals are products derived from food sources that are claimed to provide extra health benefits in addition to the basic nutritional value found in foods. These products may claim to prevent chronic diseases, improve health, delay the ageing process, increase life expectancy, or support the structure or function of the body.

 

CLA supplementation was shown to improve the lean mass to body fat ratio, decreasing fat deposition especially on the abdomen, and enhancing muscle growth. It reduces body fat by enhancing insulin sensitivity so that fatty acids and glucose can pass through muscle cell membranes and away from fat tissue.⁴ Despite the positive antiobesity effect of CLA in animals, the effects of CLA on body weight and composition in humans are inconsistent and less significant than those observed in animals^{.5, 6, 7} Studies in humans and human adipocytes have demonstrated that t10c12 CLA is the anti adipogentic isomer of CLA.⁸

Research on the biological functions and health benefits of CLA dates back to 1980s when Ha et al ⁹ made the seminal observation that CLA mixtures isolated from grilled beef or from a base categorized isomerisation of linoleic acid, inhibited chemically induced skin neoplasia in mice. This discovery led to many further studies examining the beneficial effects of CLA from different aspects including cancer, immune function, atherosclerosis, weight gain, food/energy intake, as well as body composition.^{10, 11}

 

Effects of CLA on body weight have been investigated in different rodent models. Some studies have consistently shown reductions of weight gain by feeding CLA while others have not shown any effect. Studies that have not shown a significant reduction on weight gain generally are those having applied either low levels of CLA or CLA mixtures that contained low concentrations of the t10c12 isomer.

 

MATERIAL AND METHODS:

Aim and objectives:

Aim: To study the effects of Conjugated linoleic acid in reducing body fat mass and lipid profile

 

Primary objective:

1. To evaluate the change in the body fat mass as measured by Karada scan and by anthropometric measurements.

2. To assess the change in lipid profile after treatment with Conjugated linoleic acid.

 

Secondary objective:

1. To estimate the HS-CRP, before and after treatment with Conjugated linoleic acid

2. To observe the adverse drug events during the study period.

 

Study design:

Hospital-based prospective, interventional, open and non-randomized clinical study.

 

Study setting:

Central out-patient department of GSL Medical college, Rajamahendravaram (AP)

 

Study period:

3 months

 

Study population:

22 subjects selected by simple random sampling who satisfy the selection criteria are included in the study.

Age group and sex:

Subjects of either sex from 18-65 years age group are included in the study.

 

Inclusion criteria:

1. Age between 18-65 years old of both the sexes.

2. Patients with Grade II obesity and above. (Body mass index of 30 kg /sq meter or more)

3. Waist circumference of > 104 cm in men >88 cm in women

 

Exclusion Criteria:

1. Endocrine disorders (Thyroid and pituitary disorders, diabetes mellitus)

2. Allergic disorders

3. Pregnancy and lactation

4. Patients on treatment of obesity

5. Management for weight control within previous 3 months.

6. Any other condition deemed unsuitable for trial

 

METHODOLOGY:

22 subjects, who volunteered for the study, were counselled and motivated for weight reduction before the start of the study. Baseline values of lipid profile and Highly Sensitive C-Reactive Protein (HS-CRP) are recorded. Readings taken with karada scan body composition monitor are body weight, BMI, fat percentage, visceral fat, skeletal muscle percentage and subcutaneous fat.

 

Anthropometric measurements were also taken along with the readings of Omron Karada scan to assess the validity of the instrument.

 

The various anthropometric measurements are height, weight, body mass index and skin fold thickness at the following 5 places. They are- triceps, biceps, subscapular, suprailiac and midabdominal. In all the 5 places 3 readings are taken and the average calculated.

Body fat percentage calculation done according to the formula-Adult body fat%= (1.20x BMi)+ (0.23xAge)-(10.8xsex)-5.4 where sex is 1 for male and 0 for female.

The test drug CLA given in the dose of 500mg twice per day after food for 3 months. At the end of the study, measurements are taken again. HS-CRP and lipid profile values are recorded. For all the 22 subjects, diet and exercise are standardized.

 

Omron karada scan body composition monitor HBF-701 was used to measure the body weight, body fat percentage, visceral fat , skeletal muscle percentage and subcutaneous fat. Subcutaneous fat and sketetal muscle are measured at 4 places, ie whole body, trunk, legs and arms. Age according to the fat level is measured.

 

Measuring principle of Omron Karada scan:

Calculation of body fat in accordance with the resistance value:

Karada scan measures body resistance by using weak currency flowing through both hands and both the feet by bioelectrical impedance analysis.

 

 

Bioelectrical impedance analysis (BIA):

Is an instrument used for measuring the body fat percentage designed by the Omron company. BIA is useful method to assess the body fat content and also skeletal muscle percentage. BIA determines the resistance to the flow of current as it passes through the body, it provides estimates of low conductivity from bone and fat.

 

Tissues with more water content in the human body tend to conduct electricity easily. Fat tissue almost conducts no electricity.

 

Ethical Issues:

Prior permission from the institutional ethics committee taken and informed consent taken from all the participants.

 

Statistical analysis: (For full scale study):

1. All descriptive statistics expressed in mean + standard deviation.

2. Body fat mass before and after treatment with CLA analyzed by paired t-test.

3. HS-CRP before and after treatment with CLA analyzed by paired t-test

4. Treatment emergent adverse reactions expressed in frequency and percentage.

5. All statistical analysis was done by using SPSS software version 21 and MS-EXCEL 2010.

 

Observation and Results:

The pilot study was conducted for a period of 3 months from 20-10-2016 to 20-1-2017. 22 patients were enrolled for the pilot study of which there are 2 dropouts and in the remaining 20 patients remarkable weight loss in between 3-5 kgs noticed in 12 patients. The weight reduction is about 5-8%.

 

In 2 patients skin fold thickness reduced after treatment though there is no weight loss and in 1 patient fat percentage reduced. In 5 subjects, there is no change in body weight, fat percentage or skin fold thickness. Where there is elevation in the lipid levels and HS- CRP at baseline, a reduction of the levels observed after 3 months treatment with Conjugated Linoleic Acid.

 

Table 1 Age Distribution of cases in Pilot Study

 

Table 2 Sex Distribution of cases in Pilot Study

 

Table 3 Results of the Pilot Study as measured by Karada Scan before and after treatment with CLA

 

DISCUSSION:

A pilot study has been conducted on 22 volunteers of BMI 30 or above 30 . There are 2 dropouts after a time period of one month and they discontinued the treatment. In 12 subjects, it was observed that there was weight reduction of about 5-8%. In 2 patients. Skin fold thickness reduced and in 1subject, fat percentage was reduced. There is no change in 5 subjects. Adverse events with the drug were not seen in any of the subjects.

Many rodent studies have showed the weight lowering effect of Conjugated linoleic acid. In a study conducted by Delany et al it was found that feeding male mice with a high fat diet containing 1% CLA, reduced the body weight by day 22 and the effect remained throughout the relatively long period of 12 weeks.¹²

 

Dietary CLA decreases adiposity in different animal models including mice, rats, hamsters and pigs. It has been reported that diet supplementation with CLA at a level as low as 0.5%, reduced fat deposition in both male and female ICR mice. In a long term study, female C57BL/6J mice showed an ablation of brown adipose tissue and marked decrease of subcutaneous white adipose tissue after supplemented with 1.0% CLA for 5 months. ¹³

 

Reduction of fat deposition induced by dietary CLA have also been reported in rat models. In male Sprague-Dawley rats fed diets containing 4, 7 or 10% added fat, supplementation of 1.5% CLA for 3 weeks significantly reduced white adipose tissue weight. Being consistent with the reduction of fat deposition, overall body fat content has been shown to be reduced while body protein content was increased after CLA supplementation.¹⁴

 

One of the effects of CLA that has been observed consistently is its ability to alter the fatty acid composition of tissues by reducing the levels of monounsaturated fatty acids. A proper ratio of saturated to unsaturated fatty acids is important in maintaining the membrane fluidity; alteration of this ratio can influence a variety of physiological responses including adiposity, metabolic rate and insulin sensitivity, all of which are affected by CLA. The CLA-induced reduction of fat deposition appears to be a result of decreased lipid accumulation of adipocytes. One of the key enzymes in lipid metabolism is adipocyte LPL, which hydrolyzes the circulating triglycerides and release fatty acids, which are then taken and reesterified by the adipocytes. The inhibition of LPL activity is significantly correlated with the suppressing effect of CLA on lipogenesis¹⁵

 

Previous studies conducted on animals have confirmed the ability of CLA to increase fatty acid oxidation. The t10c12 and c9t11 CLA were preferentially oxidized compared with linoleic acid over a 2 hr period in rats. Interestingly CLA also induces an increase in fat oxidation. Martin et al reported that hepatic and adipose Carnitine Palmitoyl Transferase (CPT) activity, a rate-limiting enzyme for fatty acid beta oxidation, was increased in rats after consuming a diet containing 1% of the t10c12 CLA for 6 weeks. Moreover, rats fed mixed CLA isomers produced lower respiratory quotients, indicating increased oxidation in the body. These results, together with other studies,¹⁶ suggest that CLA increases fat oxidation. The effects of CLA on human body fat mass have been investigated on several occasions. A few studies showed slight reduction of body fat mass. Thom et al ¹⁷ examined the efficacy of CLA on fat mass in healthy exercising humans with normal body weight. It was found that supplementation of 1.8g / day of CLA for 12 weeks reduced body fat. The mechanisms through which CLA reduces body weight and fat deposition remain to be fully understood. Proposed antiobesity mechanisms of CLA include decreased energy/ food intake and increased energy expenditure, decreased preadipocyte differentiation and proliferation, decreaded lipogenesis, and increased lipolysis and fat oxidation.

 

Results of in vitro studies have suggested that CLA possesses antioxidative properties¹⁸. Some human studies showed slight reductions of body fat mass or calculated fat percentage after CLA supplementation ¹⁹ while others failed to show any effect²⁰. The effect of CLA on insulin sensitivity and glucose control are also inconsistent.

 

In conclusion most of the evidence of CLA efficacy in reducing fat mass comes from animal studies, especially those conducted in mice. It is indicated that in humans the main anti adipogenic isomer is t10c12, the effects of CLA on fat deposition are less significant and more equivocal as compared to results observed in animals. There is need to conduct more trials in humans to assess the efficacy of specific CLA isomers which are critically important in ensuring the development of safe and efficacious foods fortified with CLA, or CLA based neutraceuticals for the prevention or treatment of diet-related obesity. when these neutraceuticals are employed in the treatment of obesity, the adverse events associated with the use of conventional medicines can be reduced and the quality of life can be improved much.

 

CONFLICT OF INTEREST:

There is no conflict of interest.

 

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Received on 18.09.2017         Modified on 24.10.2017

Accepted on 01.11.2017      © RJPT All right reserved