Introduction

Alpha-lipoic acid (ALA) or thiocitic acid is an eight-carbon, sulfur-containing compound. It functions as a cofactor in the multienzyme complexes that catalyze the oxidative decarboxylation of α-keto acids.1 There is general agreement about the antioxidant properties of ALA, which is thought to work by scavenging free radicals directly, chelating metallic ions, increasing intracellular glutathione and activating endogenous antioxidant systems.2, 3 ALA’s antioxidant properties are thought to inhibit the deleterious mechanisms associated with inflammation; however, a number of studies suggest contradictory effects for ALA on inflammatory markers such as IL-6 and C-reactive protein (CRP).4, 5, 6 Apart from the antioxidant properties of ALA, it is found to increase nitric oxide synthesis through which endothelial function is probably improved.7 In addition, ALA reduces body weight and changes other anthropometric indices by suppressing appetite and increasing metabolism.8, 9, 10, 11, 12

Spinal cord injury (SCI) is a devastating condition and entails considerable burden on the individual and society.13, 14 Persons with chronic SCI are at increased risk for obesity, cardiovascular disease, hypertension, diabetes, dyslipidemia and systemic inflammation15, 16, 17, 18, 19 because of changes in their lifestyle, body composition and fat mass.20 However, these complications may be preventable and treatable.21

Studying the effect of ALA on cardiovascular risk factors and dietary intake is not novel; however, the effects of ALA supplementation in persons with SCI have not been investigated yet. This study examined the effect of ALA supplementation on inflammation, energy balance and some chronic disease markers in males with chronic SCI.

Materials and methods

The protocol of this randomized, double-blind, placebo-controlled clinical trial was approved by the research Ethics Committee of Tehran University of Medical Sciences (TUMS) and was registered in the Iranian Registry of Clinical Trial (IRCT201106122602N6).

Male volunteers with SCI were referred to Imam Khomeini Hospital and upon meeting the study criteria were enrolled into this study (from June 2012 to December 2013) after obtaining their consent. The inclusion criteria included complete SCI since at least 1 year with a maximum of 10 years, body mass index (BMI)⩾18.5, age 30–50 years, no self-reported specific diseases and malignancies, no vitamin and antioxidant supplementation and no smoking and drinking. Study volunteers were excluded for failure to follow trial guidelines (<80% compliance). Participants were randomly allocated to two numerically equal groups from a double-blind, 70-person list, using a table of random digits and given either 600 mg ALA or a placebo wheat flour capsule. Study participants, as well as the placebo group, ingested those pills once daily before breakfast for 12 weeks. Twelve participants were excluded during the study (because of unwillingness, infection, ulcer, diarrhea and rash), which left 28 volunteers in the ALA group and 30 in the placebo group.

At the beginning of the study, written consent was obtained. Trained personnel performed all data collection and measurements. Body weight for the study participants was measured to the nearest 0.1 kg with minimal clothing by means of a digital wheelchair balance. To measure height, knee height was determined and the following formula22 was used: height in cm (for men)=64.19−(0.04 × Age)+(2.02 × knee height in cm).

BMI was calculated for each patient (BMI=weight in kg/height2 in m). Waist circumference was measured at the level of the iliac crest using an Ergonomic Circumference Measuring Tape (model 201; Seca GmbH & Co., KG, Hamburg, Germany). Blood pressure was measured with a mercury sphygmomanometer after 5 min of sitting rest. The average of three readings was used for the waist circumference and blood pressure measurements. Food intake was collected by 24-hour food recall (3-day recall before, and the same after intervention). A nutritionist completed questionnaires during face-to-face interviews. To assess energy and macronutrient intake, dietary data were analyzed using Nutritionist IV software (Version 4.1, First Databank Division, The Hearst Corporation, San Bruno, CA, USA).

After a 12 -h overnight fast, venous blood samples were collected. After centrifugation, the serum samples were frozen and stored at −70 °C.

All biochemical measurements were recorded in the Laboratory of Biochemistry, School of Public Health, Tehran University of Medical Sciences. IL-6 was measured with ELISA (using a kit from Orgenium Company, Finland). The method of measurement of hs-CRP was turbidimetry using Roche kits on the Cobas Auto analyzer. Fasting blood sugar (FBS) was measured by means of an enzymatic method (using a Hitachi 750 instrument, Elitech kit from Feppim Company, French).

SPSS (version 16; SPSS Inc, Chicago, IL, USA) was used for all statistical analyses. Descriptive statistics are presented as mean±s.d. The normality of data was checked by the Kolmogorov–Smirnov test (K–S test). A paired t-test (in case of normal distribiution) or a nonparametric statistical test, Wilcoxon (in case of non-normal distribiution), was used for comparing data within groups. An independent t-test (in case of normal distribution) or a nonparametric statistical test, Mann–Whitney (in case of non-normal distribiution), was used for comparing data between two groups. Adjustment for differences in baseline covariates and changes in variables during the study were studied by means of analysis of covariance (ANCOVA). All tests were two-sided and P-values <0.05 were considered statistically significant.

Results

Baseline characteristics were similar in the ALA and placebo groups (Table 1). No statistically significant differences were found for age, weight, height and disease duration between the two groups.

Table 1 Baseline characteristics of the study subjects who received α-lipoic acid (600 mg) or placebo before the intervention
Full size table

After the intervention period no significant reduction was found in IL-6 and hs-CRP levels. There was significant reduction in FBS, body weight, BMI, waist circumference, blood pressure, carbohydrate, protein, fat and energy intake (Table 2).

Table 2 Anthropometric, hypertension, dietary, and serum variables of subjects of study before and after α-lipoic acid supplementation and changes in variables during the intervention
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Discussion

The present study shows that a 12-week supplementation with 600 mg ALA in chronic SCI male patients does not change IL-6 and hs-CRP levels but decreases fasting blood sugar, anthropometric indices, food intake and blood pressure. To our knowledge, this is the first study to investigate the effect of ALA supplementation on cardiovascular risk factors in men with chronic SCI.

Our results indicate no significant effect of ALA supplementation on serum levels of IL-6 and hs-CRP. Consistent with the present study, in a randomized, placebo-controlled clinical trial, Ramos et al.6 studied the effect of tocopherol (666 IU) and lipoic acid (LA; 600 mg) combination in patients with chronic renal failure for 2 months but found no significant change in IL-6 and hs-CRP. In contrast, in two studies by Sola et al.4 (Clinical trial, 300 mg LA, 4 weeks, in subjects with metabolic syndrome) and Khabbazi et al.5 (Clinical trial, 600 mg ALA, 8 weeks, in patients with ESRD on hemodialysis) ALA supplementation reduced IL-6 and CRP (%18.7) levels, respectively. As mentioned, there are major differences between our study participants and those in other studies, such as changes in lifestyle, body composition and fat mass,20 that predispose them to show different responses to the same interventions.

We found significant effect of ALA supplementation on FBS in SCI patients. Evidence suggests that this effect of ALA may be mediated by increasing GLUT-4 transportation to muscle and fat cell membranes and increasing glucose uptake.23 An intravenous injection of 1000 mg LA improves insulin sensitivity and insulin-stimulated metabolic clearance rate in patients with type II diabetes.24 Another study reported a positive effect of oral administration of supplemental LA on insulin sensitivity and metabolic clearance rate in patients with type II diabetes.25 In a randomized, double-blind, placebo-controlled clinical trial, Ansar et al.26 noted that ALA supplementation (300 mg, 8 weeks) could improve FBS and insulin resistance in patients with type II diabetes.

Our result shows that a 12-week ALA supplementation has beneficial effects on anthropometric indices (body weight, BMI and waist circumference) and food intake in SCI patients. There is a large body of growing evidence showing that LA can have a substantial role in the regulation of food intake and anthropometric indices by suppressing appetite and elevating energy metabolism.8, 9, 11, 12 In agreement with our study there are two human studies; in a randomized, double-blind, placebo-controlled, 20-week trial, 1800 mg LA reduced body weight significantly more than did 1200 mg LA and placebo in 360 obese individuals.10 In a case series study by Kim et al.,9 the effect of LA on body weight gain induced by antipsychotics in schizophrenic patients was studied (N=7, 1200 mg LA, 12 weeks). Mean weight loss was 3.2 kg and a remarkable reduction in BMI was observed. Neither of the aforementioned studies measured food intake and only the latter assessed BMI changes with a small sample size. These limitations make it difficult to compare our results with those of other studies. ALA-induced appetite suppression is likely the major cause of changes in anthropometric indices in our study.

We found significant reduction in systolic and diastolic blood pressure after 12 weeks of LA supplementation in SCI patients. It has been suggested that LA affects blood pressure by increasing reduced glutathione (GSH) levels in tissues. It is thought to work by affecting glutathione peroxidase activity and elevating nitric oxide production in endothelial cells.3, 7, 27 Several animal studies introduced LA as a blood pressure regulator.28, 29, 30, 31, 32 In a randomized clinical trial, Mazloom and Ansar33 reported that systolic and diastolic blood pressure significantly improved following 8 weeks of 300 mg LA supplementation in type II diabetes patients. Noori et al.34 observed significant reduction in systolic blood pressure but no change in diastolic blood pressure after 12 weeks of combined administration of LA (800 mg) and pyridoxine (80 mg) in patients with diabetic nephropathy. Two prior studies showed contrasting result to our findings. In one study, Sola et al.4 examined the effect of LA, Irbesartan and their combination vs placebo in patients with metabolic syndrome, but found no significant effect on blood pressure. In the second study, the impact of LA on endothelial function and proteinuria in quinapril-treated diabetic patients with stage I hypertension was assessed and found to not have a significant effect on blood pressure.35 A possible contributing factor to the difference found between our clinical trial and the two aforementioned contrasting studies could be the inherent physical differences associated with our patients with SCI.

Several limitations must be considered in the interpretation of our findings, including limited duration of the clinical trial and the sample size. Furthermore, because of budget limitation we were not able to include healthy individuals and compare the results of SCI patients with them, and measure other inflammatory markers or total antioxidant capacity. It seems to be a need for further studies.

In conclusion, on the basis of the present study results, it can be concluded that ALA supplementation (600 mg, 12 weeks) improves FBS, anthropometric indices, food intake and blood pressure but has no effect on measured inflammatory markers in men with chronic SCI.

Data archiving

There were no data to deposit.