Effects of Alpha-Lipoic Acid Supplementation on Plasma Adiponectin Levels and Some Metabolic Risk Factors in Patients with Schizophrenia

Abstract

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

Introduction

Schizophrenia is a severe psychiatric disorder with reduced life expectancy and higher physical-health comorbidity rate more than the general population.¹ Genetic predisposition, sedentary lifestyle, poor diet, as well as metabolic side effects related to antipsychotic treatment, has contributed to the high prevalence of obesity and obesity-related complications in patients with schizophrenia.²

In recent years, a number of pathophysiological processes have been identified in schizophrenia, including oxidative stress, one-carbon metabolism, and immune-mediated responses. Thus, there is considerable interest in ameliorating these altered physiological mechanisms by nutritional intervention, as an adjunct antipsychotic treatment, including antioxidant and vitamin B supplementation, neuroprotective and anti-inflammatory nutrients, as well as exclusion diets.³ Especially, the nutraceuticals for raising cellular glutathione (GSH) level in the brain and other tissues with high metabolic rates could be highly beneficial in patients with schizophrenia.⁴

The metabolic syndrome is a cluster of cardiometabolic conditions, generally triggered by an expansion of the adipose visceral tissue, which include insulin resistance, with or without impairing glucose metabolism and type 2 diabetes, atherogenic dyslipidemia [low high-density lipoprotein (HDL) cholesterol and high triglycerides], and high blood pressure.⁵ Insulin resistance is associated with fat accumulation in the liver, a condition called nonalcoholic fatty liver disease (NAFLD), in its whole spectrum ranging from the pure fatty liver to nonalcoholic steatohepatitis, which has been identified as the hepatic manifestation of the metabolic syndrome.⁶ In addition to the diagnostic importance of the presence, NAFLD can also be associated with the risk of future development of metabolic syndrome.⁷

Although the precise mechanisms are still unclear, dysregulated production or secretion of bioactive substances, known as adipocytokines, caused by excess adipose tissue and adipose tissue dysfunction may play a critical role in the pathogenesis of the metabolic syndrome, including NAFLD.⁸ In fact, a number of these adipocytokines have been linked to alterations in insulin sensitivity, including adiponectin, leptin, resistin, and tumor necrosis factor-α (TNF-α).⁹ Unlike, other adipokines, serum adiponectin concentrations are decreased in obesity and obesity-related complications.¹⁰ Based on its insulin-sensitizing, anti-inflammatory, and antiatherogenic properties, an increase in circulating adiponectin may have beneficial effects in the prevention and treatment of hepatic insulin resistance, metabolic syndrome, and related complications.¹¹ Pharmacological intervention and lifestyle modification such as restriction of calorie intake in combination with moderate physical activity have been shown to increase plasma adiponectin levels.^12,13 Although the mechanism is still poorly understood, increased intake of some nutrients, such as the long chain polyunsaturated fatty acids (LC-PUFAs), also has been shown to increase adiponectin levels.¹⁴

Recent studies have shown that supplementation with alpha-lipoic acid (ALA) could help to improve obesity treatment and/or reduce the comorbidities related to an excessive fat storage.^15,16 ALA or its reduced form, dihydrolipoic acid (DHLA), has many biochemical functions acting as biological antioxidants and modulators of the signaling transduction of several pathways.¹⁷ Some positive metabolic effects of ALA/DHLA have been proposed to be mediated by the modulation of the central and the peripheral 5′-AMP-activated protein kinase and the activation of the transcription factor PPAR-γ that increases adiponectin expression and production in adipocytes.¹⁸ However, there is no clear evidence of proper dose of ALA in the potential treatment of obesity and metabolic disorders.^4,16

Taking into account all these facts, the aim of our study was to investigate whether adjunctive ALA supplementation (500 mg per day) for 3 months affects the plasma adipokine concentrations (adiponectin and leptin) in patients with schizophrenia. We also aim to identify anthropometric and biochemical parameters correlated with adiponectin concentration in schizophrenic patients.

Materials and Methods

Subjects

The study was undertaken according to the Helsinki declaration and was approved by the Ethics Committee of the Clinical Center of Serbia in Belgrade. Eighteen patients (10 female and 8 male), aged between 25 and 60 years, who maintained a stable dose of their current antipsychotic for at least 2 months before enrollment were recruited from the outpatient unit of the Clinic for Psychiatry, Clinical Center of Serbia, Belgrade. International Classification of Diseases (ICD-10) criteria was used to obtain the diagnosis of schizophrenia. The Clinical Global Impression (CGI) scale was used to measure the severity of the psychotic disorder, as well as the changes in severity of illness ratings from baseline. Exclusion criteria were as follows: the current substance or alcohol abuse; the presence of significant medical illness, including severe head injury, seizure disorders, diabetes, cancer, renal, or liver diseases; patients who underwent treatment with hypolipidemic or hypoglycemic drugs; or taking of any supplements at least 30 days prior the study beginning. All subjects gave signed informed consent before the enrollment. They were instructed to take the ALA capsules (500 mg) once a day before breakfast and to maintain their usual dietary habits and lifestyle throughout the study. They also were advised to continue their antipsychotic drugs as usual. To monitor compliance, patients were asked to return any unused capsules.

Blood sampling and anthropometric measurements were performed at three time points: the baseline, in the middle, and at the end of the 3-month supplementation period.

Sample collection and analysis

Venous blood was collected into the sample tubes for serum and EDTA-containing tubes for plasma between 8 a.m. and 10 a.m. after an overnight fast. Serum and plasma were separated by centrifugation, and multiple aliquots of each sample were stored at −80°C until analysis.

Fasting glucose, lipid status parameters [total cholesterol (t-C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglycerides (TG)], and liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT)] were determined in a serum, on the same day the samples were collected, using automated analyzer (ILab300+ analyzer; Instrumentation Laboratory) and commercial kits according to the manufacturer's instruction.

The anthropometric measurements included height, weight, waist circumference, and body fat. Body height was measured without shoes using a standard height bar. Body weight and total body fat were measured with a Tanita digital scale (InnerScan Body Composition Monitor, BC 587; Tanita Corp) to the nearest 0.1 kg with the subject wearing light clothes and without shoes. Body mass index was calculated by dividing the weight in kilograms by the square of the height in meters (kg/m²). Waist circumference was measured midpoint between the iliac crest and the lowest rib.

The fatty liver index (FLI) was calculated according to the formula based on BMI, waist circumference, triglycerides, and GGT.¹⁹

Total plasma adiponectin concentration was measured in duplicate and assayed by an enzyme-linked immunosorbent assay (ELISA) method (Human Adiponectin/Acrp30 Immunoassay; Quantikine, R&D systems). The concentration of leptin in plasma was determined using a Leptin (sandwich) ELISA Kit (DRG Instruments).

As oxidative stress parameters, we determined the production of superoxide anion in plasma using an assay previously described by Auclair and Voisin²⁰ and malondialdehyde (MDA) as a by-product of lipid peroxidation according to Girotti et al. ²¹ Total antioxidant capacity (TAC) was determined by the automated method developed by Erel²² using an ILab300+ autoanalyser.

Serum lipids were extracted according to the method of Sperry and Brand,²³ which uses chloroform–methanol mixture (2:1, v/v) with 10 mg/100 mL 2,6-di-tert-butylmethylphenol (BHT) added as an antioxidant. The phospholipid fraction was isolated from the lipid extract using one-dimensional thin-layer chromatography in a neutral lipid solvent system hexane-diethyl ether-acetic acid (87:12:1, v/v/v) using Silica Gel GF plates (C. Merck). Following methylation, fatty acid ester derivatives were analyzed by gas chromatography using a Varian gas chromatograph (model 3400). Individual fatty acid methyl esters were identified by comparing peak retention times with authentic standards (Sigma-Aldrich) and/or the PUFA-2 standard mixtures (Supelco, Inc.). The results were expressed as the relative percentage of total identified fatty acids (FA). The percentage of total saturated fatty acids (SFAs) was calculated as the sum of the percentages of C16:0 and C18:0, while the percentage of monounsaturated fatty acids (MUFAs) was determined from C16:1n-7, C18:1n-9, and C18:1n-7 percentages. The percentage of total PUFAs was calculated from the percentages of individual polyunsaturated long-chain fatty acids C18:2n-6, C20:3n-6, C20:4n-6, C22:4n-6, C20:5n-3, C22:5n-3, and C22:6n-3.

Statistical analyses

Data are shown as the mean and standard deviation for normally distributed variables and as the geometric mean and 95th confidence intervals derived from log-normal values. Comparisons were performed by repeated measures analysis of variance with the Bonferroni post hoc test. Logarithmic transformation of glucose, TG, and O₂ ⁻ values was performed because of the skewed distribution in an analysis using repeated measures analysis of variance. Associations of the investigated parameters and adiponectin concentrations were evaluated by Spearman's rho correlation test. Multiple linear regression analysis was performed to estimate the independent association of the investigated parameters with adiponectin concentrations. All statistical analyses were performed using the SPSS software (version 18.0). All statistical tests were considered significant at the 0.05 probability level.

Results

The general characteristics of the study group at baseline are presented in Table 1. The study included 10 females and 8 men who were schizophrenia patients with average age 39.7 ± 8.4 years and BMI 26.7 ± 5.4. A detailed description of the clinical characteristics of the study population has been described in our previous article.²⁴ Briefly, all patients were of the chronic type, with an average duration of illness 11.4 ± 5.4 years and CGI score 3.6 ± 0.7. All the patients were receiving various antipsychotic medications at conventional doses, including clozapine (n = 9), risperidone (n = 4), olanzapine (n = 2), as well as haloperidol (n = 2) and chlorpromazine (n = 1). In terms of additional medications, six patients received benzodiazepines, five received valproic acid, and four received an anticholinergic medication.

Table 1.

Baseline Characteristics of the Study Population

Characteristics
Age (years)	39.7 ± 8.4
Body weight (kg)	85.38 ± 22.79
BMI (kg/m²)	26.7 ± 5.4
Waist circumference (cm)	98.6 ± 15.7
Body fat (%)	31.0 ± 8.9
Leptin (ng/mL)^a	6.89 (3.92–9.87)
Adiponectin (ng/mL)^a	8135 (5672–11666)
Glucose (mM)^a	6.01 (5.40–6.67)
ALT (U/L)	15.37 ± 7.15
AST (U/L)	27.73 ± 5.71
GGT (U/L)	19.06 ± 8.70
Triglycerides (mM)^a	1.91 (1.18–3.09)
Total cholesterol (mM)	6.36 ± 1.38
LDL cholesterol (mM)	3.99 ± 0.86
HDL cholesterol (mM)	1.19 ± 0.35
Plasma phospholipid levels (%)
SFA	43.54 ± 2.79
MUFA	10.26 ± 1.32
PUFA	46.24 ± 3.68
n-6 PUFA	41.12 ± 2.29
n-3 PUFA	5.11 ± 2.45
n-6/n-3	9.28 ± 3.15
MDA (μM)	1.52 ± 0.50
O₂ ⁻ (μmol/min/L)^a	31.9 (22.7–45.0)
TAC (μM)	775 ± 267
FLI	52.34 ± 35.27

Data are presented as mean ± SD.

–geometric mean and 95th confidence intervals derived from log-normal values. Fatty acid concentrations are expressed in % of total detected fatty acids.

FLI, fatty liver index; SFA, saturated fatty acid; MDA, malondialdehyde; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; TAC, total antioxidant capacity.

Correlation analyses considering adiponectin concentrations, anthropometric, biochemical, and parameters of the oxidative stress status in patients with schizophrenia were performed (Table 2).

Table 2.

Spearman's Nonparametric Correlations Between Adiponectin and Baseline Biochemical, Oxidative Status Parameters and Fatty Liver Index

Parameter	r	P
Body weight (kg)	−0.681	<.01
BMI (kg/m²)	−0.622	<.01
Waist circumference (cm)	−0.762	<.001
Body fat (%)	−0.188	.455
Leptin (ng/mL)	−0.179	.478
Glucose (mM)	−0.337	.091
ALT (U/L)	−0.199	.430
AST (U/L)	−0.683	<.05
GGT (U/L)	−0.314	.205
Triglycerides (mM)	−0.612	<.01
Total cholesterol (mM)	−0.410	.091
LDL-cholesterol (mM)	−0.284	.305
HDL-cholesterol (mM)	0.344	.163
SFA	−0.355	.315
MUFA	−0.023	.949
PUFA	0.266	.458
n-6 PUFA	−0.012	.973
n-3 PUFA	0.411	.238
n-6/n-3	−0.385	.272
MDA (μM)	0.093	.714
O₂ ⁻ (μmol/min/L)	−0.486	<.05
TAC (μM)	−0.275	.364
FLI	−0.731	<.001

As expected, significant inverse correlations between plasma adiponectin and body weight (r = −0.681, P < .01), an abdominal circumference (r = −0.762, P < .001), and BMI (r = −0.622, P < .01) were found. In addition, we found that the baseline adiponectin concentration was inversely correlated with triglycerides (r = −0.612, P < .01) and AST activity (r = −0.683, P < .05). Circulating adiponectin levels were inversely correlated with O₂ ⁻ (r = −0.486, P < .05) as well. Baseline plasma adiponectin level showed strong significant negative correlations with the FLI (r = −0.713, P < .001). No significant correlations were observed between adiponectin and serum phospholipid FA levels (Table 2).

To reveal significant and independent determinants of adiponectin levels, we performed a multiple linear regression analysis (Table 3). When BMI, triglyceride concentrations, AST activities, and O₂ ⁻ levels were included in the model, only the AST activities were a significant predictor of adiponectin levels. In fact, 48.7% of the adiponectin increase could be explained by a decrease in AST activity.

Table 3.

Multiple Regression Analysis of the Association of Various Parameters in Schizophrenic Patients with Adiponectin

Adiponectin (ng/mL); R ² = 0.674; adjusted R ² = 0.487
Variables	Standardized β coefficients	P
BMI (kg/m²)	−0.727	.075
Triglycerides (mM)	0.232	.516
AST (U/L)	−0.498	<.05
O₂ ⁻ (μmol/min/L)	−0.052	.854

Table 4 presents the anthropometric, metabolic, and oxidative stress parameters and adipokines levels during the study. Statistically significant increase was observed in plasma adiponectin levels (P < .05) after 3 months of supplementation with ALA, while the plasma leptin concentration was not significantly changed. Although no statistically significant changes in anthropometric parameters were found, there was a trend toward reduction in waist circumference through the study (P = .087). There were no significant changes in the phospholipid FA serum composition, suggesting constant dietary fatty acid pattern throughout the study period. The decrease of the percentage of total SFAs, n-3 PUFAs, and total PUFAs was noticed, although not statistically relevant. In contrast, the total n-6 PUFAs slightly increased from the beginning until the end of the study, while MUFAs showed a tendency to an increase only between the midpoint and baseline (Table 4).

Table 4.

Anthropometric and Biochemical Parameters and Serum Phospholipid Fatty Acid Composition of Patients During the Study Period

	Baseline	Midpoint	End point	P
Body weight (kg)	85.38 ± 22.79	85.07 ± 23.05	85.03 ± 22.56	.748
BMI (kg/m²)	26.7 ± 5.4	26.6 ± 5.5	26.6 ± 5.4	.763
Waist circumference (cm)	98.6 ± 15.7	96.5 ± 16.3	96.9 ± 16.4	.087
Body fat (%)	31.0 ± 8.9	32.5 ± 11.3	30.5 ± 9.8	.169
Leptin (ng/mL)^a	6.89 (3.92–9.87)	6.94 (4.15–9.73)	6.78 (3.72–9.85)	.533
Adiponectin (ng/mL)^a	8135 (5672–11666)	10308 (7712–13777)	12793 (9917–16503)^*	<.01
Glucose (mM)^a	6.01 (5.40–6.67)	5.42 (5.17–5.69)^*	5.29 (5.01–5.58)^**	<.05
ALT (U/L)	15.37 ± 7.15	14.96 ± 7.46	15.37 ± 6.32	.960
AST (U/L)	27.73 ± 5.71	26.90 ± 8.00	20.45 ± 6.63^*	<.05
GGT (U/L)	19.06 ± 8.70	20.78 ± 11.19	17.58 ± 6.59	.331
Triglycerides, (mM)^a	1.91 (1.18–3.09)	2.05 (1.41–2.99)	1.93 (1.36–2.74)	.521
Total cholesterol (mM)	6.36 ± 1.38	6.39 ± 1.78	6.18 ± 1.54	.760
LDL-cholesterol (mM)	3.99 ± 0.86	4.16 ± 1.55	3.96 ± 1.30	.774
HDL-cholesterol (mM)	1.19 ± 0.35	1.14 ± 0.33	1.06 ± 0.39	.432
SFA (%)	43.54 ± 2.79	43.52 ± 2.01	42.99 ± 3.04	.789
MUFA (%)	10.26 ± 1.32	10.74 ± 1.41	10.66 ± 1.51	.673
PUFA (%)	46.24 ± 3.68	45.75 ± 3.08	45.74 ± 3.17	.927
n-6 PUFA (%)	41.12 ± 2.29	41.35 ± 2.90	41.73 ± 3.32	.862
n-3 PUFA (%)	5.11 ± 2.45	4.39 ± 0.97	4.02 ± 1.71	.287
n-6/n-3	9.28 ± 3.15	9.85 ± 2.35	10.01 ± 2.82	.620
MDA (μM)	1.52 ± 0.50	1.44 ± 0.65	1.59 ± 0.41	.782
O₂ ⁻ (μmol/min/L)^a	31.9 (22.7–45.0)	25.2 (14.7–43.1)	31.5 (25.7–38.5)	.858
TAC (μM)	775 ± 267	786 ± 134	760 ± 177	.950
FLI	52.34 ± 35.27	51.97 ± 33.45	51.95 ± 34.86	.973

Data are presented as mean ± SD.

–geometric mean and 95th confidence intervals derived from log-normal values.

Repeated measures ANOVA was used for comparisons.

P < .05; ^** P < .01.

A statistically significant decrease was observed in fasting serum glucose at the midpoint, as well as at the end point of the ALA supplementation period in comparison with the baseline (P < .05, P < .01, respectively). Furthermore, statistically significant decrease was observed in AST activity (P < .05) between the end point and baseline.

Discussion

The recognition that schizophrenia is associated with metabolic comorbidity and a subsequent greater risk of cardiovascular events compared to the general population have led to attempts to reduce this metabolic burden.²⁵ Although the antipsychotics are helpful in the management of psychotic symptoms, these drugs, especially second-generation antipsychotics, have the potential to cause weight gain and other metabolic syndrome-related side effects.²⁶ In this context, more recent research has focused on identifying safe and effective adjunctive antiobesity therapeutic options in schizophrenia.³

Although studies are limited, there is clinical support of an antiobesity effect of ALA in schizophrenia patients. In a study by Kim et al.,²⁷ daily consumption of ALA (1200 mg) for 12 weeks was associated with reduced body weight in patients with schizophrenia without significant adverse effects. In another study, Ratliff et al. ²⁸ also reported significant weight loss in nondiabetic schizophrenia patients consuming 1200 mg/ALA over 10 weeks. In contrast with these results, our data showed that the daily supplementation with the lower dose of ALA (500 mg) was not effective for weight loss in antipsychotic medicated patients with schizophrenia.²⁴

In addition to weight reduction, there is evidence that ALA exerts many beneficial metabolic effects.^29,30 However, it is currently unclear whether these effects are secondary to weight loss or if they are the product of a more direct molecular effect of ALA.

In the current study, we found that ALA supplementation for 3 months significantly increases the plasma adiponectin concentrations in patients with schizophrenia. Our result is in agreement with the animal model study who suggest that the ability of ALA to prevent insulin resistance might be related to the stimulation of AMPK and increased expression of receptors for adiponectin in white adipose tissue.³¹ Furthermore, adiponectin through upregulation of AMPK activity has direct actions in the liver, skeletal muscle, and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation, and attenuate TNF-α mediated vascular inflammation.³² In the general population, the serum adiponectin level has been found to be inversely correlated with body weight, especially visceral adiposity, as well as other metabolic risk factors such as insulin, triglycerides, and very low-density lipoprotein (LDL) cholesterol, while positively correlated with HDL cholesterol.³³ This study found an inverse correlation of adiponectin with anthropometric measures and hypertriglyceridemia confirming that low adiponectin levels could be associated with overweight, obesity, and higher metabolic adversities in patients taking second-generation antipsychotics, particularly clozapine and olanzapine.^34

–38 Recently, it was shown that the changes in adiponectin levels appeared to be a direct effect of antipsychotics on hormonal pathways of energy homeostasis, rather than the result of weight gain,³⁹ but this concept needed to be more documented.

Interestingly, in our study the baseline plasma adiponectin concentrations were inversely correlated with plasma superoxide anions, suggesting that adiponectin and oxidative stress might have a close association with cardiometabolic risk factors in schizophrenia. This result is not surprising because a number of studies already established that lower adiponectin concentrations were associated with higher concentrations of inflammatory markers, higher concentrations of oxidative stress markers, and lower antioxidant enzyme activities, which are characteristics of metabolic syndrome, diabetes, and cardiovascular disease.⁴⁰ In addition, experimental cellular models showed that adiponectin directly suppresses superoxide generation in endothelial cells.⁴¹ But, after ALA supplementation for 3 months, an inverse correlation between adiponectin and superoxide anion was lost (data not shown). The explanation for this losing of correlation is in the fact that after the period of supplementation adiponectin concentration was significantly higher compared with the baseline concentration, while superoxide anion concentration showed a decrease, but it was not statistically significant (Table 4). According to this result, we could speculate that the short-term effect of ALA supplementation (3 months) is more effective on adiponectin as adipocytokine and that potential effect of ALA supplementation on oxidative stress parameters should be investigated for a long period of supplementation.

Available evidence suggests that insulin resistance affects the hepatic fat accumulation by increasing the release of free fatty acids from adipose tissue, increasing fatty acid and triglyceride synthesis in the liver, reducing fatty acid oxidation, and increasing very LDL production.^42,43 Data from our study showed that the baseline plasma adiponectin concentration was negatively correlated with the FLI, which recently suggested as the most reliable early predictor of metabolic syndrome.⁴⁴ It has recently been shown that adiponectin correlates negatively with cardiometabolic risk factors and is an independent indicator for NAFLD.⁴⁵ In addition, our data clearly showed a very strong and independent association of liver enzyme AST with the baseline adiponectin level (Table 3). In logistic regression analysis, AST remained as a significant predictor of low adiponectin level, even after adjustment for BMI, triglyceride, and O₂ ⁻ levels. The observed relationships with low adiponectin in the baseline revealed through multiple regression analysis were completely lost at the end of the supplementation period. The greater plasma adiponectin concentration is accompanied by significant decrease in the AST activities at the end of the study. Considering that elevated liver aminotransferase levels are the primary abnormalities seen in patients with NAFLD, we can speculate that the risk of NAFLD in schizophrenia is associated with a decrease in adiponectin concentration. In accordance with this, it was recently shown that adiponectin inversely correlated with transaminase levels, even within normal ranges, in a large population-based cohort and suggested that adiponectin should be evaluated as possible NAFLD-specific liver injury markers, especially in individuals at risk for metabolic syndrome.⁴⁶

Despite existing data indicating that adiponectin levels were associated with plasma phospholipid FA composition in overweight and obese nondiabetic adults,^33,47 no significant correlations were observed in our study. There is substantial evidence that adiponectin expression and serum levels are associated with the amount and type of dietary fats. In general, it has been suggested that SFAs have negative associations with adiponectin levels, while ω-3 PUFAs are positive.⁴⁸ At the same time, there was no change in phospholipid FA composition during treatment with ALA. The main problems in the measurement of dietary intake of FA are that some tools used to assess dietary intake of FA are subjective and the quality of data for FA content of foods in databases can be low. From those reasons, plasma phospholipid FA composition was being increasingly used as an indicator of dietary fat quality. Plasma phospholipid FA is primarily related to medium-term (weeks to months) qualitative dietary intake of fats and endogenous metabolism of FA.⁴⁹ Although endogenous FA metabolism in schizophrenia might be associated with fatty acid desaturase gene polymorphism⁵⁰ (that is not prone to medium-term changes), it can be suggested that dietary fat quality was not changed during the study and that dietary FAs had no influence on adiponectin levels.

The limitations of the present study, including the relatively small number of patients, the lack of a placebo group, and open-label design, should be taken into account. Furthermore, the patients were under treatment with various antipsychotic drugs with different potential for adverse metabolic effects. In addition, although patients were asked to maintain their eating and exercise habits, characteristics of their diet and level of physical activity could not be documented.

In conclusion, supplementation with ALA had some beneficial effects on plasma adiponectin, as well as glucose and AST levels in patients with schizophrenia. Based on the present data, ALA using adiponectin-dependent mechanisms may be useful in the control and prevention of metabolic complications in antipsychotic medicated schizophrenic patients such as the metabolic syndrome and NAFLD.

Footnotes

Acknowledgment

The authors acknowledge financial support from the Ministry of Education and Science of Serbia, project numbers III46001, III41030, and 175035.

Author Disclosure Statement

No competing financial interests exist.

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