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Hosseinzadeh M, Pakravanfar F, Ghadiri-Anari A, Fallahzadeh H. The Effect of L-Carnitine Supplementation on Weight and Body Composition in Women with Polycystic Ovary Syndrome: A Double-Blind Randomized Clinical Trial. JNFS 2020; 5 (3) :282-289
URL: http://jnfs.ssu.ac.ir/article-1-298-en.html
URL: http://jnfs.ssu.ac.ir/article-1-298-en.html
Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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The Effect of L-Carnitine Supplementation on Weight and Body Composition in Women with Polycystic Ovary Syndrome: A Double-Blind Randomized Clinical Trial
Fatemeh Pakravanfar; MSc 1, Akram Ghadiri-Anari; MD 3, Azadeh Nadjarzadeh; PhD 1, 2,Hossein Fallahzadeh; PhD 3 & Mahdieh Hosseinzadeh; PhD *1, 2
1 Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
2 Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
3 Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
2 Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
3 Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
| ARTICLE INFO | ABSTRACT | |
| ORIGINAL ARTICLE | Background: Polycystic ovarian syndrome (PCOS), one of the most common causes of endocrine disorders with irregular menstruation, is accompanied by an increase in androgen and polycystic ovarian. The aim of this study was to evaluate the effect of weight loss regimen with and without supplementation. L-carnitine affects lipid profile, insulin, and hormone resistance indices. Methods: This double-blind randomized clinical trial was conducted over women within the age range of 18 to 45 years, who referred to Yazd Diabetes Center in 2019. The participants were divided into the experimental and control groups. The intervention group received 1000 mg L-carnitine (LG = 28) and the placebo group (PG = 28) received the placebo daily. All people followed a low celery diet for 12 weeks. Anthropometric indices and body composition (weight, body mass index, waist circumference, hip circumference, fat mass, and free fat mass) were measured prior to and after the intervention. Data analysis was performed using SPSS software version 22. The independent sample t-test was used to compare the mean changes between the LG and PG. Results: At the end of the study period, patients treated with L-carnitine showed a significant decrease in waist circumference compared to the PG (change: -1 ± 3.15, P = 0.001) and no significant difference was observed between the two groups in terms of other anthropometrics indices and body composition including fat mass, body mass index, and hip circumference (P > 0.05). Conclusion: The present study showed that 1000 mg oral L-carnitine had no significant effect on body weight, body mass index, body composition, and hip circumference, but had a significant effect on waist circumference size. Keywords: Polycystic ovarian syndrome; L-carnitine; Androgenic index; Sex hormone-binding globulin |
|
| Article history: Received: 28 Jan 2020 Revised: 21 Jun 2020 Accepted: 6 May 2020 |
||
| IRCT20191016045131N1 | ||
| *Corresponding author: hoseinzade.mahdie@gmail.com Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Postal code: 8915173160 Tel: +98- 9126992113 |
Introduction
Polycystic ovary syndrome (PCOS) was first reported in modern medical literature describing seven women with amenorrhea, hirsutism, and ovaries enlarged with multiple cysts (Azziz, 2004). Disorders affecting women with PCOS are characterized by high levels of androgens, dysfunction of the ovaries and polycystic ovaries. The clinical manifestations of PCOS are very different. Women with PCOS often seek care for menstrual disorders, hyperandrogenism, and infertility (Sirmans and Pate, 2014).
The prevalence of PCOS varies according to different criteria. According to NIH/NICHD data, its prevalence in Australia and Iran was 8.7% and 7-7.1%, respectively. The disability-adjusted life year (DALY) index of PCOS is ranked 22nd in Iran in 2010 (Forouzanfar et al., 2014). The prevalence of PCOS is high in people with insulin resistance and metabolic syndrome (Panidis et al., 2008). Polycystic ovary syndrome has important clinical complications including psychological problems (decreased quality of life, decreased self-esteem, depression, and anxiety), fertility manifestations (prematurity, infertility, and pregnancy complications), and metabolic consequences (insulin resistance, metabolic syndrome, and diabetes mellitus) (Teede et al., 2010). They are also at risk for endometrial carcinoma, hypertension, and dyslipidemia (Knochenhauer et al., 1998). Genetics play an important role in the pathogenesis of this disease. People with a history of weight gain develop clinical symptoms of PCOS (Sirmans and Pate, 2014).
Treatment modalities include lifestyle adjustment, obesity treatment, drug therapy (Legro, 2012), and symptoms related to androgens, menstruation,
and infertility that include oral contraceptive pill (OCP) medications, Spironolactone, Metformin, Thiazolinedione Clomiphene citrate etc. (Sirmans and Pate, 2014). Studies were conducted over the effect of zinc (Foroozanfard et al., 2015), calcium, vitamin D (Pal et al., 2012), selenium (Razavi et al., 2016), omega 3 (Sadeghi et al., 2017), myoinositol (Emekçi Özay et al., 2017), folate (Bahmani et al., 2014), and chromium (Jamilian et al., 2016)
on PCOS. Given that obesity is one of the
effective factors on PCOS, weight loss is
considered as an infertility treatment in women
with overweight/obesity (Jiskoot et al., 2017). Obesity is associated with insulin resistance (Rafraf et al., 2012), which increases insulin, decreases steroid hormone binding globulin (SHBG(, increases circulating free testosterone, and results in ovarian follicle development (Teede et al., 2010). Carnitine is a trimethylamine, produced in the liver by lysine and methionine, and plays an important role in the metabolism of cellular energy. Its mechanism of action involves increasing glucose oxidation as well as improving insulin sensitivity under insulin-dependent conditions. Hyperinsulinemia increases carnitine accumulation in muscle and decreases serum carnitine (Fenkci et al., 2008). Carnitine is found in two forms of L-Carnitine, which is the active form, and D carnitine, which is the biologically inactive form (Ismail et al., 2014).
Studies investigated the effects of L-Carnitine on diseases such as severe ischemia, knee osteoarthritis, coronary artery disease, hypothyroidism, diabetes, and hyperlipidemia (Kumar et al., 2015). However, limited data are available regarding its effect on ovarian syndrome. For example, two studies reported that low serum carnitine levels were associated with an increased incidence of this syndrome. Furthermore, two studies found that high-dose carnitine treatment in PCOS improved fertility, congestion, lipid profile, weight loss, waist circumference and hip circumference (Ismail et al., 2014, Samimi et al., 2016).
Given the high prevalence of PCOS, the limited number of studies over the effect of L-Carnitine on PCOS, and the fact that no study has ever evaluated the combined effect of weight loss diet and L-Carnitine supplementation, the present study was conducted. The aim of this study was to investigate the effect of weight loss regimen with and without L-Carnitine supplementation on anthropometric indices and body composition.
Materials and Methods
Design and Population: In this double-blind study, the sample size was calculated as 31 using the significance level of 0.05, the test power of 80%, and according to the average insulin level of 26.03 (Samimi et al., 2016). The L-Carnitine and placebo supplements were codified as A or B by an individual who was unaware of the study process and goals. Later, random allocation tables were applied using computer software and participants were allocated into the intervention or control groups.
Intervention group (CG) members were supposed to take 1000 mg L-Carnitine capsules daily and the placebo group (PG) consumed the exactly similar placebo supplements in lunch meal for 12 weeks. Every two weeks the participants were supposed to refer to the researcher, bring the empty capsule bottles, and receive the next bottle. A trained researcher also checked the participants' adherence to the diet.
Administration dose and Follow-up: The L-Carnitine capsules and placebo were obtained from Karen Corporation in Yazd city. The weight loss diet was designed by calculating the basal daily energy for each person using the Harris Benedict formula (Movahedi, 1999). To this end, the total energy consumed, the activity coefficient, and the thermic effect food were considered for each individual. In order to decrease the participants' weight, 500 kcal was reduced from the final calculated energy required for each participant.
Measurements: The patients’ weights were also measured on a portable digital scale (Omeron BF511, Japan) to the nearest 0.1 kg. Waist circumference (midpoint between the upper edge of the iliac and the last rib) and hip circumference (the widest part of the hip) were measured using a plastic meter prior to and after the intervention. Body mass index (BMI) was also calculated after dividing weight (kg) by squared height (m). Furthermore, height was measured in standing position using an audiometer fixed on a straight wall to the nearest 0.1 cm. Participants were also required to complete the consent forms, demographic questionnaire containing information, items about education, age, gender, etc., items about disease and medication history, and the 24-hour food recall questionnaire.
Ethical Considerations: The patients freely volunteered to participate in this study and could withdraw from the study as they wished. Written informed consent forms were obtained from all participants. In addition, the study proposal was approved by Ethics-in-Research Commission in Shahid Sadoughi University of Medical Sciences (IR.SSU.SPH.REC.1397.014). Moreover, this study was registered in Iranian randomized
clinical trial (www.irct.ir). With the code of IRCT20191016045131N1.
Data analysis: SPSS software version 22 was used for data analysis. Paired sample t-test was used to assess within-group changes. Independent sample student t-test was also run to compare the mean changes between the intervention and control groups. Non-parametric equivalent tests were applied for abnormal data. Meanwhile, the significance level of all tests was set at 0.05.
Results
This study was conducted on 62 patients with PCOS, who referred to Yazd Diabetes Center. As shows the figure 1, a total of 58 participants completed the study; three patients were excluded from the study due to pregnancy (in the PG) and three others did not want to continue the study
(CG = 28, PG = 28).
The individual characteristics of patients at the beginning of the study are shown in Table 1. No significant difference was found between the
study groups in terms of the anthropometric characteristics and age at the baseline (P > 0.05). The mean age of participants was 30.79 ± 6.57 years and their mean of BMI was 30.6 ± 5.85. Table 2 includes the anthropometric changes before and 12 weeks after the intervention in both groups. Weight loss, BMI, as well as waist and hip circumference were significantly different before and after the intervention for the CG. However, only waist circumference was significantly different between the two groups
(P = 0.001) and other anthropometric indices were not significant (P > 0.05).
The prevalence of PCOS varies according to different criteria. According to NIH/NICHD data, its prevalence in Australia and Iran was 8.7% and 7-7.1%, respectively. The disability-adjusted life year (DALY) index of PCOS is ranked 22nd in Iran in 2010 (Forouzanfar et al., 2014). The prevalence of PCOS is high in people with insulin resistance and metabolic syndrome (Panidis et al., 2008). Polycystic ovary syndrome has important clinical complications including psychological problems (decreased quality of life, decreased self-esteem, depression, and anxiety), fertility manifestations (prematurity, infertility, and pregnancy complications), and metabolic consequences (insulin resistance, metabolic syndrome, and diabetes mellitus) (Teede et al., 2010). They are also at risk for endometrial carcinoma, hypertension, and dyslipidemia (Knochenhauer et al., 1998). Genetics play an important role in the pathogenesis of this disease. People with a history of weight gain develop clinical symptoms of PCOS (Sirmans and Pate, 2014).
Treatment modalities include lifestyle adjustment, obesity treatment, drug therapy (Legro, 2012), and symptoms related to androgens, menstruation,
and infertility that include oral contraceptive pill (OCP) medications, Spironolactone, Metformin, Thiazolinedione Clomiphene citrate etc. (Sirmans and Pate, 2014). Studies were conducted over the effect of zinc (Foroozanfard et al., 2015), calcium, vitamin D (Pal et al., 2012), selenium (Razavi et al., 2016), omega 3 (Sadeghi et al., 2017), myoinositol (Emekçi Özay et al., 2017), folate (Bahmani et al., 2014), and chromium (Jamilian et al., 2016)
on PCOS. Given that obesity is one of the
effective factors on PCOS, weight loss is
considered as an infertility treatment in women
with overweight/obesity (Jiskoot et al., 2017). Obesity is associated with insulin resistance (Rafraf et al., 2012), which increases insulin, decreases steroid hormone binding globulin (SHBG(, increases circulating free testosterone, and results in ovarian follicle development (Teede et al., 2010). Carnitine is a trimethylamine, produced in the liver by lysine and methionine, and plays an important role in the metabolism of cellular energy. Its mechanism of action involves increasing glucose oxidation as well as improving insulin sensitivity under insulin-dependent conditions. Hyperinsulinemia increases carnitine accumulation in muscle and decreases serum carnitine (Fenkci et al., 2008). Carnitine is found in two forms of L-Carnitine, which is the active form, and D carnitine, which is the biologically inactive form (Ismail et al., 2014).
Studies investigated the effects of L-Carnitine on diseases such as severe ischemia, knee osteoarthritis, coronary artery disease, hypothyroidism, diabetes, and hyperlipidemia (Kumar et al., 2015). However, limited data are available regarding its effect on ovarian syndrome. For example, two studies reported that low serum carnitine levels were associated with an increased incidence of this syndrome. Furthermore, two studies found that high-dose carnitine treatment in PCOS improved fertility, congestion, lipid profile, weight loss, waist circumference and hip circumference (Ismail et al., 2014, Samimi et al., 2016).
Given the high prevalence of PCOS, the limited number of studies over the effect of L-Carnitine on PCOS, and the fact that no study has ever evaluated the combined effect of weight loss diet and L-Carnitine supplementation, the present study was conducted. The aim of this study was to investigate the effect of weight loss regimen with and without L-Carnitine supplementation on anthropometric indices and body composition.
Materials and Methods
Design and Population: In this double-blind study, the sample size was calculated as 31 using the significance level of 0.05, the test power of 80%, and according to the average insulin level of 26.03 (Samimi et al., 2016). The L-Carnitine and placebo supplements were codified as A or B by an individual who was unaware of the study process and goals. Later, random allocation tables were applied using computer software and participants were allocated into the intervention or control groups.
Intervention group (CG) members were supposed to take 1000 mg L-Carnitine capsules daily and the placebo group (PG) consumed the exactly similar placebo supplements in lunch meal for 12 weeks. Every two weeks the participants were supposed to refer to the researcher, bring the empty capsule bottles, and receive the next bottle. A trained researcher also checked the participants' adherence to the diet.
Administration dose and Follow-up: The L-Carnitine capsules and placebo were obtained from Karen Corporation in Yazd city. The weight loss diet was designed by calculating the basal daily energy for each person using the Harris Benedict formula (Movahedi, 1999). To this end, the total energy consumed, the activity coefficient, and the thermic effect food were considered for each individual. In order to decrease the participants' weight, 500 kcal was reduced from the final calculated energy required for each participant.
Measurements: The patients’ weights were also measured on a portable digital scale (Omeron BF511, Japan) to the nearest 0.1 kg. Waist circumference (midpoint between the upper edge of the iliac and the last rib) and hip circumference (the widest part of the hip) were measured using a plastic meter prior to and after the intervention. Body mass index (BMI) was also calculated after dividing weight (kg) by squared height (m). Furthermore, height was measured in standing position using an audiometer fixed on a straight wall to the nearest 0.1 cm. Participants were also required to complete the consent forms, demographic questionnaire containing information, items about education, age, gender, etc., items about disease and medication history, and the 24-hour food recall questionnaire.
Ethical Considerations: The patients freely volunteered to participate in this study and could withdraw from the study as they wished. Written informed consent forms were obtained from all participants. In addition, the study proposal was approved by Ethics-in-Research Commission in Shahid Sadoughi University of Medical Sciences (IR.SSU.SPH.REC.1397.014). Moreover, this study was registered in Iranian randomized
clinical trial (www.irct.ir). With the code of IRCT20191016045131N1.
Data analysis: SPSS software version 22 was used for data analysis. Paired sample t-test was used to assess within-group changes. Independent sample student t-test was also run to compare the mean changes between the intervention and control groups. Non-parametric equivalent tests were applied for abnormal data. Meanwhile, the significance level of all tests was set at 0.05.
Results
This study was conducted on 62 patients with PCOS, who referred to Yazd Diabetes Center. As shows the figure 1, a total of 58 participants completed the study; three patients were excluded from the study due to pregnancy (in the PG) and three others did not want to continue the study
(CG = 28, PG = 28).
The individual characteristics of patients at the beginning of the study are shown in Table 1. No significant difference was found between the
study groups in terms of the anthropometric characteristics and age at the baseline (P > 0.05). The mean age of participants was 30.79 ± 6.57 years and their mean of BMI was 30.6 ± 5.85. Table 2 includes the anthropometric changes before and 12 weeks after the intervention in both groups. Weight loss, BMI, as well as waist and hip circumference were significantly different before and after the intervention for the CG. However, only waist circumference was significantly different between the two groups
(P = 0.001) and other anthropometric indices were not significant (P > 0.05).
| Figure 1. Flowchart of intervention |
| Table 1. Selected baseline characteristics of study participants | |||||
| P-valuea | Placebo group (n = 28) |
L-carnitine group ( n = 28) | Total (n = 56) |
Variables | |
| 0.95 | 30.83 ± 6.53 | 30.74 ± 6.71 | 30.79 ± 6.57 | Age (y) | |
| 0.79 | 30.8 ± 6.40 | 31.01 ± 4.62 | 30.60 ± 5.85 | Body mass index (kg/m2) | |
| 0.33 | 163.5 ± 3.00 | 162.00 ± 49.17 | 162.60 ± 5.50 | Height (cm) | |
| 0.77 | 82.27 ± 1.20 | 81.42 ± 1.30 | 81.85 ± 1.24 | Weight (kg) | |
| 0.72 | 99.00± 10.00 | 99.00 ± 11.00 | 99.08 ± 10.20 | Waist (cm) | |
| 0.45 | 115.35 ± 94.35 | 113.37 ± 11.20 | 114.36 ± 10.31 | Hip (cm) | |
| 0.85 | 26.84 ± 3.72 | 26.63 ± 5.52 | 26.74 ± 4.49 | Free fat mass (%) | |
| 0.85 | 40.71 ± 6.57 | 41.01 ± 7.37 | 40.88 ± 6.92 | Fat mass (%) | |
| a: Student t-test | |||||
| Table.2: Anthropometric variable changes in patients treated with placebo and L-carnitine before and after 12 weeks of intervention | ||||
| Variables | Before | After | P-valuea | Changes |
| Body mass index (kg/m2) L-carnitine group Placebo group P-valueb |
81.42 ± 1.30 82.27 ± 1.20 0.66 |
79.59 ± 1.20 81.94 ± 1.26 0.77 |
0.04 0.39 |
-1.83 ± 4.6 -0.20 ± 1.2 0.11 |
| Weight (kg) L-carnitine group Placebo group P-value |
31.01 ± 4.62 30. 80 ± 6.40 0.45 |
30.24 ± 4.46 32.27 ± 1.20 0.79 |
0.04 0.68 |
-0.77 ± 2.01 -0.08 ± 0.56 0.10 |
| Waist circumference (cm) L-carnitine group Placebo group P-value |
99.98 ± 11.63 99.00 ± 10.00 0.56 |
96.99 ± 8.93 99.00 ± 11.00 0.72 |
0.002 0.66 |
-1.0 ± 3.15 0.001 ± 0.0 0.11 |
| Hip circumference (cm) L-carnitine group Placebo group P-value |
113.37 ± 11.20 115.35 ± 94.35 0.25 |
112.10 ± 10.54 115.03 ± 95.75 0.45 |
0.01 0.11 |
-1.0 ± 2.0 0.001 ± 1.0 0.12 |
| Free fat mass (%) L-carnitine group Placebo group P-value |
26.63 ± 5.20 26.84 ± 3.72 0.84 |
26.82± 5.93 27.07 ± 4.01 0.85 |
0.89 0.58 |
-1.0 ± 5.5 0.7 ± 0.8 0.46 |
| Fat mass (%) L-carnitine group Placebo group P-value |
41.04 ± 7.37 40.71 ± 6.57 0.93 |
40.45 ± 8.68 40.81 ± 6.85 0.85 |
0.81 0.84 |
-0.39 ± 9.2 0.10 ± 1.2 0.92 |
| a: Pared t-test; b: Student t-test | ||||
Discussion
The effect of L-Carnitine on anthropometric indices showed that supplementation with 1000 mg L-Carnitine for three months did not lead to a significant weight loss in the two studied groups. A significant decrease was observed in the waist circumference between the two groups. The
results of studies in this area are contradictory.
For example, L-Carnitine administration (15 mg/kg/day) did not affect weight loss among bipolar patients treated with valproate for 26 weeks on a low-fat diet (Elmslie et al., 2006). Furthermore, oral L-Carnitine supplementation had no effect on weight loss in patients with impaired glucose metabolism (Molfino et al., 2010) and in obese women (Villani et al., 2000). A study over people with PCOS showed no significant decrease in weight, BMI, and waist circumference after taking 250 mg L-Carnitine supplementation daily for 12 weeks (Samimi et al., 2016). A study conducted in 2013 evaluated the effect of L-Carnitine supplementation for eight weeks with a daily dose of 2 g in obese women with type 2 diabetes who underwent low calorie diet. After intervention, a significant decrease was found in anthropometric indices of the intervention group, however, this decrease was not significant compared to the control group (Barzegar et al., 2013).
The results of our study are in contradiction with the results of a study in which 250 mg L-Carnitine was administered for a 12-week intervention period. This study showed a significant decrease in BMI and weight of the intervention group compared with the control group (Jamilian et al., 2017).
In animal studies, L-Carnitine supplementation resulted in significant weight loss in the intervention group (Center et al., 2000). In another study, clomiphene citrate-resistant PCOS women were required to intake 1 mg/day L-Carnitine for 5 weeks. The findings showed a significant reduction in BMI of the intervention group (Ismail et al., 2014). A meta-analysis over 7 randomized controlled trials found a significant reduction in weight and BMI of patients who used 1.8 to 4 g of L-Carnitine daily (Pooyandjoo et al., 2016). A recent meta-analysis conducted in 2019 showed that different doses of L-Carnitine (less than 2 g daily) reduced body weight and BMI, but had no effect on body fat percentage. This meta-analysis showed that a dose of less than 2 g did not affect body fat mass (Center et al., 2012).
Empirical evidences also show that L-Carnitine stimulates pyruvate dehydrogenase complex activity by reducing acetyl-CoA to CoA after trapping acetyl groups. Simultaneous depletion of CoA acetyltransferase in the cytosol is further involved in activation of the glycolytic pathway. So, L-Carnitine plays a key role in the metabolism of glucose and assists in fuel-sensing (Barzegar et al., 2013).
L-Carnitine intake may decrease body weight, BMI, waist circumference, and hip circumference by increasing beta-oxidation of fatty acids (Askarpour et al., 2020) and increasing basal metabolic rate (Seim et al., 2002).
In our study, the observed weight loss and BMI decrease in the L-Carnitine group confirms the results of previous studies. However, these changes were not significant compared to the control group, which could be explained by administration of the low calorie diet in both study groups.
Strength of this study includes investigation of PCOS patients in terms of their compliance with a low calorie diet by taking into account the effect of L-Carnitine supplementation. Weaknesses of the study are administration of a low dose of L-Carnitine and short duration of the intervention. Furthermore, we could not measure the participants' hormone levels, lipid profile, and glycemia.
Conclusion
Based on the findings, the weight loss and BMI reduction were only observed in the L-Carnitine group. However, these changes were not significant compared to the control group, which can be justified by administration of a low calorie diet in both groups.
Conflict of interest
The authors declare that they have no competing interests.
Funding
Financial support for this study was provided by School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Authors' contributions
Hosseinzadeh M designed the study concept and revised the manuscript. Pakravanfar F collected the data and prepared the manuscript. Fallahzadeh H performed the statistical analyses. Nadjarzadeh A was also involved in designing the study and revising the manuscript. Ghadiri A was also involved in designing the study and revising the manuscript.
Acknowledgements
We appreciate all participants of the study for their cooperation.
The effect of L-Carnitine on anthropometric indices showed that supplementation with 1000 mg L-Carnitine for three months did not lead to a significant weight loss in the two studied groups. A significant decrease was observed in the waist circumference between the two groups. The
results of studies in this area are contradictory.
For example, L-Carnitine administration (15 mg/kg/day) did not affect weight loss among bipolar patients treated with valproate for 26 weeks on a low-fat diet (Elmslie et al., 2006). Furthermore, oral L-Carnitine supplementation had no effect on weight loss in patients with impaired glucose metabolism (Molfino et al., 2010) and in obese women (Villani et al., 2000). A study over people with PCOS showed no significant decrease in weight, BMI, and waist circumference after taking 250 mg L-Carnitine supplementation daily for 12 weeks (Samimi et al., 2016). A study conducted in 2013 evaluated the effect of L-Carnitine supplementation for eight weeks with a daily dose of 2 g in obese women with type 2 diabetes who underwent low calorie diet. After intervention, a significant decrease was found in anthropometric indices of the intervention group, however, this decrease was not significant compared to the control group (Barzegar et al., 2013).
The results of our study are in contradiction with the results of a study in which 250 mg L-Carnitine was administered for a 12-week intervention period. This study showed a significant decrease in BMI and weight of the intervention group compared with the control group (Jamilian et al., 2017).
In animal studies, L-Carnitine supplementation resulted in significant weight loss in the intervention group (Center et al., 2000). In another study, clomiphene citrate-resistant PCOS women were required to intake 1 mg/day L-Carnitine for 5 weeks. The findings showed a significant reduction in BMI of the intervention group (Ismail et al., 2014). A meta-analysis over 7 randomized controlled trials found a significant reduction in weight and BMI of patients who used 1.8 to 4 g of L-Carnitine daily (Pooyandjoo et al., 2016). A recent meta-analysis conducted in 2019 showed that different doses of L-Carnitine (less than 2 g daily) reduced body weight and BMI, but had no effect on body fat percentage. This meta-analysis showed that a dose of less than 2 g did not affect body fat mass (Center et al., 2012).
Empirical evidences also show that L-Carnitine stimulates pyruvate dehydrogenase complex activity by reducing acetyl-CoA to CoA after trapping acetyl groups. Simultaneous depletion of CoA acetyltransferase in the cytosol is further involved in activation of the glycolytic pathway. So, L-Carnitine plays a key role in the metabolism of glucose and assists in fuel-sensing (Barzegar et al., 2013).
L-Carnitine intake may decrease body weight, BMI, waist circumference, and hip circumference by increasing beta-oxidation of fatty acids (Askarpour et al., 2020) and increasing basal metabolic rate (Seim et al., 2002).
In our study, the observed weight loss and BMI decrease in the L-Carnitine group confirms the results of previous studies. However, these changes were not significant compared to the control group, which could be explained by administration of the low calorie diet in both study groups.
Strength of this study includes investigation of PCOS patients in terms of their compliance with a low calorie diet by taking into account the effect of L-Carnitine supplementation. Weaknesses of the study are administration of a low dose of L-Carnitine and short duration of the intervention. Furthermore, we could not measure the participants' hormone levels, lipid profile, and glycemia.
Conclusion
Based on the findings, the weight loss and BMI reduction were only observed in the L-Carnitine group. However, these changes were not significant compared to the control group, which can be justified by administration of a low calorie diet in both groups.
Conflict of interest
The authors declare that they have no competing interests.
Funding
Financial support for this study was provided by School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Authors' contributions
Hosseinzadeh M designed the study concept and revised the manuscript. Pakravanfar F collected the data and prepared the manuscript. Fallahzadeh H performed the statistical analyses. Nadjarzadeh A was also involved in designing the study and revising the manuscript. Ghadiri A was also involved in designing the study and revising the manuscript.
Acknowledgements
We appreciate all participants of the study for their cooperation.
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Center SA, et al. 2012. Influence of dietary supplementation with (L)-carnitine on metabolic rate, fatty acid oxidation, body condition, and weight loss in overweight cats. American Journal of Veterinary Research. 73 (7): 73, 1002.
Elmslie JL, Porter RJ, Joyce PR, Hunt PJ & Mann JI 2006. Carnitine does not improve weight loss outcomes in valproate-treated bipolar patients consuming an energy-restricted, low-fat diet. Bipolar Disorders. Bipolar Disorders. 8 (5p1): 503-507.
Emekçi Özay Ö, Özay AC, Çağlıyan E, Okyay RE & Gülekli B 2017. Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: a prospective, controlled, randomized trial. Gynecological Endocrinology. 33 (7): 524-528.
Fenkci SM, Fenkci V, Oztekin O, Rota S & Karagenc N 2008. Serum total L-carnitine levels in non-obese women with polycystic ovary syndrome. Human Reproduction. 23 (7): 1602-1606.
Foroozanfard F, et al. 2015. Effects of zinc supplementation on markers of insulin resistance and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Experimental and Clinical Endocrinology & Diabetes. 123 (04): 215-220.
Forouzanfar MH, et al. 2014. Evaluating causes of death and morbidity in Iran, global burden of diseases, injuries, and risk factors study 2010. Archives of Iranian Medicine. 17 (5): 304.
Ismail AM, Hamed AH, Saso S & Thabet HH 2014. Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial. European Journal of Obstetrics & Gynecology and Reproductive Biology. 180: 148-152.
Jamilian H, et al. 2017. Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinology. 33 (6): 442-447.
Jamilian M, et al. 2016. The effects of chromium supplementation on endocrine profiles, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biological Trace Element Research. 172 (1): 72-78.
Jiskoot G, et al. 2017. A three-component cognitive behavioural lifestyle program for preconceptional weight-loss in women with polycystic ovary syndrome (PCOS): a protocol for a randomized controlled trial. Reproductive Health. 14 (1): 34.
Knochenhauer E, et al. 1998. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. Journal of Clinical Endocrinology & Metabolism. 83 (9): 3078-3082.
Kumar NS, Kalaivanam K, Bheemasen R, Chandrappa MS & Ramadas D 2015. A view of L-carnitine in health and disease. Journal of Pharmaceutical Research. 5 (8).
Legro RS 2012. Obesity and PCOS: implications for diagnosis and treatment. In Seminars in reproductive medicine, pp. 496-506. Thieme Medical Publishers.
Molfino A, et al. 2010. Caloric restriction and L-carnitine administration improves insulin sensitivityin patients with impaired glucose metabolism. Journal of Parenteral and Enteral Nutrition. 34 (3): 295-299.
Movahedi A 1999. Simple formula for calculating basal energy expenditure. Nutrition Research. 19 (7): 989-995.
Pal L, et al. 2012. Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. Gynecological Endocrinology. 28 (12): 965-968.
Panidis D, et al. 2008. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertility and Sterility. 89 (4): 899-906.
Pooyandjoo M, Nouhi M, Shab-Bidar S, Djafarian K & Olyaeemanesh A 2016. The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. докринологія. 23 (1): 83-90.
Rafraf M, Karimi M, Rashidi M & Jafari A 2012. Effect of l-carnitine supplementation in comparison with moderate aerobic training on insulin resistance and anthropometric indices in obese women. Journal of Advances in Medical and Biomedical Research. 20 (83): 17-30.
Razavi M, et al. 2016. Selenium supplementation and the effects on reproductive outcomes, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome. Hormone and Metabolic Research. 48 (03): 185-190.
Sadeghi A, Djafarian K, Mohammadi H & Shab-Bidar S 2017. Effect of omega-3 fatty acids supplementation on insulin resistance in women with polycystic ovary syndrome: Meta-analysis of randomized controlled trials. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 11 (2): 157-162.
Samimi M, et al. 2016. Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled trial. Clinical endocrinology. 84 (6): 851-857.
Seim H, Kiess W & Richter T 2002. Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults. Metabolism-Clinical and Experimental,. 51 (11): 1389-1391.
Sirmans S & Pate K 2014. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology. 6 (1): 1.
Teede H, Deeks A & Moran L 2010. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Medicine. 8 (1): 41.
Villani RG, Gannon J, Self M & Rich P 2000. L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. International Journal of Sport Nutrition and Exercise Metabolism, . 10 (2): 199-207.
Askarpour M, et al. 2020. Beneficial Effects of L-Carnitine Supplementation for Weight Management in Overweight and Obese Adults: An Updated Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. Pharmacological Research. 151: 104554.
Azziz R 2004. PCOS: a diagnostic challenge. Reproductive biomedicine online. 8 (6): 644-648.
Bahmani F, Karamali M, Shakeri H & Asemi Z 2014. The effects of folate supplementation on inflammatory factors and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled clinical trial. Clinical Endocrinology. 81 (4): 582-587.
Barzegar A, Panahi F & Karamzad N 2013. Effect of L-carnitine supplementation on serum adipokines (leptin and visfatin) levels in obese type II diabetes mellitus women with hypocaloric diet. Life Science Journal. 10: 359-365.
Center SA, et al. 2000. The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L‐carnitine. Journal of Veterinary Internal Medicine. 14 (6): 598-608.
Center SA, et al. 2012. Influence of dietary supplementation with (L)-carnitine on metabolic rate, fatty acid oxidation, body condition, and weight loss in overweight cats. American Journal of Veterinary Research. 73 (7): 73, 1002.
Elmslie JL, Porter RJ, Joyce PR, Hunt PJ & Mann JI 2006. Carnitine does not improve weight loss outcomes in valproate-treated bipolar patients consuming an energy-restricted, low-fat diet. Bipolar Disorders. Bipolar Disorders. 8 (5p1): 503-507.
Emekçi Özay Ö, Özay AC, Çağlıyan E, Okyay RE & Gülekli B 2017. Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: a prospective, controlled, randomized trial. Gynecological Endocrinology. 33 (7): 524-528.
Fenkci SM, Fenkci V, Oztekin O, Rota S & Karagenc N 2008. Serum total L-carnitine levels in non-obese women with polycystic ovary syndrome. Human Reproduction. 23 (7): 1602-1606.
Foroozanfard F, et al. 2015. Effects of zinc supplementation on markers of insulin resistance and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Experimental and Clinical Endocrinology & Diabetes. 123 (04): 215-220.
Forouzanfar MH, et al. 2014. Evaluating causes of death and morbidity in Iran, global burden of diseases, injuries, and risk factors study 2010. Archives of Iranian Medicine. 17 (5): 304.
Ismail AM, Hamed AH, Saso S & Thabet HH 2014. Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial. European Journal of Obstetrics & Gynecology and Reproductive Biology. 180: 148-152.
Jamilian H, et al. 2017. Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinology. 33 (6): 442-447.
Jamilian M, et al. 2016. The effects of chromium supplementation on endocrine profiles, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biological Trace Element Research. 172 (1): 72-78.
Jiskoot G, et al. 2017. A three-component cognitive behavioural lifestyle program for preconceptional weight-loss in women with polycystic ovary syndrome (PCOS): a protocol for a randomized controlled trial. Reproductive Health. 14 (1): 34.
Knochenhauer E, et al. 1998. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. Journal of Clinical Endocrinology & Metabolism. 83 (9): 3078-3082.
Kumar NS, Kalaivanam K, Bheemasen R, Chandrappa MS & Ramadas D 2015. A view of L-carnitine in health and disease. Journal of Pharmaceutical Research. 5 (8).
Legro RS 2012. Obesity and PCOS: implications for diagnosis and treatment. In Seminars in reproductive medicine, pp. 496-506. Thieme Medical Publishers.
Molfino A, et al. 2010. Caloric restriction and L-carnitine administration improves insulin sensitivityin patients with impaired glucose metabolism. Journal of Parenteral and Enteral Nutrition. 34 (3): 295-299.
Movahedi A 1999. Simple formula for calculating basal energy expenditure. Nutrition Research. 19 (7): 989-995.
Pal L, et al. 2012. Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. Gynecological Endocrinology. 28 (12): 965-968.
Panidis D, et al. 2008. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertility and Sterility. 89 (4): 899-906.
Pooyandjoo M, Nouhi M, Shab-Bidar S, Djafarian K & Olyaeemanesh A 2016. The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. докринологія. 23 (1): 83-90.
Rafraf M, Karimi M, Rashidi M & Jafari A 2012. Effect of l-carnitine supplementation in comparison with moderate aerobic training on insulin resistance and anthropometric indices in obese women. Journal of Advances in Medical and Biomedical Research. 20 (83): 17-30.
Razavi M, et al. 2016. Selenium supplementation and the effects on reproductive outcomes, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome. Hormone and Metabolic Research. 48 (03): 185-190.
Sadeghi A, Djafarian K, Mohammadi H & Shab-Bidar S 2017. Effect of omega-3 fatty acids supplementation on insulin resistance in women with polycystic ovary syndrome: Meta-analysis of randomized controlled trials. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 11 (2): 157-162.
Samimi M, et al. 2016. Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled trial. Clinical endocrinology. 84 (6): 851-857.
Seim H, Kiess W & Richter T 2002. Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults. Metabolism-Clinical and Experimental,. 51 (11): 1389-1391.
Sirmans S & Pate K 2014. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology. 6 (1): 1.
Teede H, Deeks A & Moran L 2010. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Medicine. 8 (1): 41.
Villani RG, Gannon J, Self M & Rich P 2000. L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. International Journal of Sport Nutrition and Exercise Metabolism, . 10 (2): 199-207.
Type of article: orginal article |
Subject:
public specific
Received: 2020/01/28 | Published: 2020/07/27 | ePublished: 2020/07/27
Received: 2020/01/28 | Published: 2020/07/27 | ePublished: 2020/07/27
References
1. Askarpour M, et al. 2020. Beneficial Effects of L-Carnitine Supplementation for Weight Management in Overweight and Obese Adults: An Updated Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. Pharmacological Research. 151: 104554.
2. Azziz R 2004. PCOS: a diagnostic challenge. Reproductive biomedicine online. 8 (6): 644-648.
3. Bahmani F, Karamali M, Shakeri H & Asemi Z 2014. The effects of folate supplementation on inflammatory factors and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled clinical trial. Clinical Endocrinology. 81 (4): 582-587.
4. Barzegar A, Panahi F & Karamzad N 2013. Effect of L-carnitine supplementation on serum adipokines (leptin and visfatin) levels in obese type II diabetes mellitus women with hypocaloric diet. Life Science Journal. 10: 359-365.
5. Center SA, et al. 2000. The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L‐carnitine. Journal of Veterinary Internal Medicine. 14 (6): 598-608.
6. Center SA, et al. 2012. Influence of dietary supplementation with (L)-carnitine on metabolic rate, fatty acid oxidation, body condition, and weight loss in overweight cats. American Journal of Veterinary Research. 73 (7): 73, 1002.
7. Elmslie JL, Porter RJ, Joyce PR, Hunt PJ & Mann JI 2006. Carnitine does not improve weight loss outcomes in valproate-treated bipolar patients consuming an energy-restricted, low-fat diet. Bipolar Disorders. Bipolar Disorders. 8 (5p1): 503-507.
8. Emekçi Özay Ö, Özay AC, Çağlıyan E, Okyay RE & Gülekli B 2017. Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: a prospective, controlled, randomized trial. Gynecological Endocrinology. 33 (7): 524-528.
9. Fenkci SM, Fenkci V, Oztekin O, Rota S & Karagenc N 2008. Serum total L-carnitine levels in non-obese women with polycystic ovary syndrome. Human Reproduction. 23 (7): 1602-1606.
10. Foroozanfard F, et al. 2015. Effects of zinc supplementation on markers of insulin resistance and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Experimental and Clinical Endocrinology & Diabetes. 123 (04): 215-220.
11. Forouzanfar MH, et al. 2014. Evaluating causes of death and morbidity in Iran, global burden of diseases, injuries, and risk factors study 2010. Archives of Iranian Medicine. 17 (5): 304.
12. Ismail AM, Hamed AH, Saso S & Thabet HH 2014. Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial. European Journal of Obstetrics & Gynecology and Reproductive Biology. 180: 148-152.
13. Jamilian H, et al. 2017. Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinology. 33 (6): 442-447.
14. Jamilian M, et al. 2016. The effects of chromium supplementation on endocrine profiles, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biological Trace Element Research. 172 (1): 72-78.
15. Jiskoot G, et al. 2017. A three-component cognitive behavioural lifestyle program for preconceptional weight-loss in women with polycystic ovary syndrome (PCOS): a protocol for a randomized controlled trial. Reproductive Health. 14 (1): 34.
16. Knochenhauer E, et al. 1998. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. Journal of Clinical Endocrinology & Metabolism. 83 (9): 3078-3082.
17. Kumar NS, Kalaivanam K, Bheemasen R, Chandrappa MS & Ramadas D 2015. A view of L-carnitine in health and disease. journal of Pharmaceutical Research. 5 (8).
18. Legro RS 2012. Obesity and PCOS: implications for diagnosis and treatment. In Seminars in reproductive medicine, pp. 496-506. Thieme Medical Publishers.
19. Molfino A, et al. 2010. Caloric restriction and L-carnitine administration improves insulin sensitivityin patients with impaired glucose metabolism. Journal of Parenteral and Enteral Nutrition. 34 (3): 295-299.
20. Movahedi A 1999. Simple formula for calculating basal energy expenditure. Nutrition Research. 19 (7): 989-995.
21. Pal L, et al. 2012. Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. Gynecological Endocrinology. 28 (12): 965-968.
22. Panidis D, et al. 2008. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertility and Sterility. 89 (4): 899-906.
23. Pooyandjoo M, Nouhi M, Shab-Bidar S, Djafarian K & Olyaeemanesh A 2016. The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. докринологія. 23 (1): 83-90.
24. Rafraf M, Karimi M, Rashidi M & Jafari A 2012. Effect of l-carnitine supplementation in comparison with moderate aerobic training on insulin resistance and anthropometric indices in obese women. Journal of Advances in Medical and Biomedical Research. 20 (83): 17-30.
25. Razavi M, et al. 2016. Selenium supplementation and the effects on reproductive outcomes, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome. Hormone and Metabolic Research. 48 (03): 185-190.
26. Sadeghi A, Djafarian K, Mohammadi H & Shab-Bidar S 2017. Effect of omega-3 fatty acids supplementation on insulin resistance in women with polycystic ovary syndrome: Meta-analysis of randomized controlled trials. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 11 (2): 157-162.
27. Samimi M, et al. 2016. Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled trial. Clinical endocrinology. 84 (6): 851-857.
28. Seim H, Kiess W & Richter T 2002. Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults. Metabolism-Clinical and Experimental,. 51 (11): 1389-1391.
29. Sirmans S & Pate K 2014. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology. 6 (1): 1.
30. Teede H, Deeks A & Moran L 2010. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Medicine. 8 (1): 41.
31. Villani RG, Gannon J, Self M & Rich P 2000. L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. International Journal of Sport Nutrition and Exercise Metabolism, . 10 (2): 199-207.
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