Powerpoint about phytochemicals

KOWSAR

Int J Endocrinol Metab. 2010;8(2):68-73

Journal home page: www.IJEM.org

Effect of garlic on serum adiponectin and interleukin levels in women with metabolic syndrome

Faranak Sharifi 1*, Abdolkarim Sheikhi 1, Mahnaz Behdad 1, Nouraddin Mousavinasab 1

1 Metabolic Diseases Research Center, Valieasr Hospital, Zanjan University of Medical Sciences, Zanjan, IR Iran

A B S T R A C T

Background: Metabolic syndrome is considered to be an inflammatory situation with highly production of adipokines. Garlic and its products are known to induce anti- inflammatory effects. However, no data are available on the anti- inflammatory effects of garlic in subjects with metabolic syndrome. Objectives: This study was designed to investigate the effects of a chemically wellchar- acterized garlic preparation on biomarkers for inflammation, and lipid metabolism in subjects with metabolic syndrome. Patients and Methods: This study was a double-blind, randomized, placebo-controlled trial in 40 adult women, aged > 18 year, who were diagnosed to have metabolic syn- drome based on ATPIII criteria and 10 normal women. The cases were randomly as- signed to 2 parallel treatment groups: garlic tablets (1.8 g/d), or placebo. Serum adi- ponectin, interleukin 6, TNF α and lipid profiles were measured at baseline and after 6 weeks of treatment and anthropometric measurements were recorded. Results: Compared to the placebo group, garlic treatment resulted in significantly low- er weight and waist circumference in women with metabolic syndrome. No effect on weight was detected in normal subjects with garlic. None of the inflammatory biomar- kers and plasma lipid levels showed significant differences between the garlic-treated and the placebo groups. Conclusions: This study confirms that garlic has no effect on major plasma lipoproteins and furthermore has no impact on inflammatory biomarkers in women with meta- bolic syndrome.

A R T I C L E I N F O

Article history: Received: 5 Jul 2010 Revised: 12 Sep 2010 Accepted: 26 Dec 2010

Keywords: Garlic Metabolic syndrome Lipids TNF alpha Interleukin 6 Adiponectin

Article Type: Original Article

Copyright c 2011, Iran Endocrine Society, Published by Kowsar M.P.Co. All rights reserved.

* Corresponding author at: Faranak Sharifi, Metabolic Diseases Research Center, Valieasr Hospital, Zanjan University of Medical Sciences, Zanjan, IR Iran. Tel: +98-9121412528, Fax: +98-2417270815.

E-mail: [email protected]

Background

Diet is a key factor in the development of some human diseases, including cardiovascular disease. The health- benefits of fruit and vegetable consumption, because of the anti-inflammatory properties of their phytochemical components, have been suggested (1). One such source is garlic (Allium sativum). The majority of garlic (65%) is water, and the bulk of the dry weight is composed of fructose-containing carbohydrates, followed by sulfur

c 2011 Kowsar M.P.Co. All rights reserved.

Please cite this paper as: Sharifi F, Sheikhi AK, Behdad M, Mousavinasab N. Effect of garlic on serum adiponectin and interleukin levels in women with meta- bolic syndrome. Int J Endocrinol Metab. 2010;8(2):68-73.

compounds, protein, fiber, and free amino acids (2). It also contains high levels of saponins, phosphorus, po- tassium, sulfur, zinc, moderate levels of selenium and Vitamins A and C, and low levels of calcium, magnesium, sodium, iron, manganese, and B-complex vitamins; gar- lic also has a high phenolic content (3). Recently interest in garlic as a preventive factor in cardiovascular diseases has increased. Some studies showed an effect for garlic in lowering plasma lipid concentrations and preventing progressive atherosclerotic changes and consequently reducing the incidence of cardiovascular events (4-6). Other studies however do not support these observa- tions and reported no significant effects on these vari- ables (7-9). Clustering of some cardiovascular risk factors such as abdominal obesity, dyslipidemias, hypertension

Int J Endocrinol Metab. 2010;8(2):68-73

69Garlic, serum adiponectin and interleukin in metabolic syndrome Sharifi F et al.

and glucose intolerance has been recognized as metabol- ic syndrome (10), of which central obesity was suggested to be the basic component. Obesity is associated with chronic inflammation due to overproduction of proin- flammatory cytokines, including tumor necrosis factor (TNF)-α. In vitro studies show that high concentrations of garlic decrease cytokine production in endothelial cells, suggesting anti-inflammatory properties (11, 12). To our knowledge, no studies have reported the effects of garlic on inflammatory biomarkers in the metabolic syndrome in humans.

Objectives

This study was designed to investigate the effects of garlic on markers of inflammation associated with CVD. In addition, the effects of garlic on plasma lipid concen- trations, fasting plasma glucose and body weight were investigated.

Patients and Methods Subjects

This is a double-blind, randomized, placebo-controlled study with 3 parallel groups. A total of 50 women, aged more than 18 years, including 40 cases with metabolic syndrome (MS) and 10 normal female controls were completed the study. All the subjects with MS were out- patients at the Endocrine Clinic of Valieasr general Hos- pital of Zanjan University of Medical Sciences, and were diagnosed with metabolic syndrome based on the ATPIII criteria (13). All the subjects with acute or chronic infec-

tion or inflammatory disorders were excluded. They were also excluded if they were smokers, pregnant or used any medication (i.e. aspirin, metformin, steroid or nonsteroidal anti-inflammatory drugs) that interferes with the measures of the study or affects insulin sensi- tivity. All the subjects with known diabetes mellitus and those with triglyceride levels over 400 mg/dL were also excluded. Normal subjects without any cardiovascular risk factors were volunteers who drawn from the same socioeconomic population. Approval for the study was obtained from the ethics committee of Zanjan Univer- sity of Medical Sciences. All participants were notified about the goals of the study, and informed consent was obtained.The study was registerd in IRCT, code number: 138706121179N1.

Study design

From a list of 102 adult subjects with known metabolic syndrome who were outpatients of endocrine clinic,50 people were selected with simple random sampling and recalled. They were randomly assigned to 1 of the 2 treat- ment arms by a nurse. The subjects received either the garlic preparation (daily dose of 1.8 g; two 300 mg garlic tablets three times per day ) or placebo (2 garlicmatching placebo tablets morning, noon and evening). An addi- tional 12 normal volunteer women were serially assigned to the third arm of the study and received garlic tablets with the same doses of the cases. The total treatment period was 6 wk with follow-up visits scheduled after 2, 4, and 6 wk. On these visits the study medication was counted, their medical history was taken and adverse

Parameter Metabolic syndrome placebo group (No. = 20)

Metabolic syndrome garlic group (No. = 20)

Normal women on garlic (No. = 20)

Before After Before After Before After

Age 47.9 ± 3 - 50.5 ± 2.9 - 49.2 ± 3.4 -

BMI a 29.1 ± 0.9 29 ± 0.8 29.6 ± 0.8 29 ± 0.9 26.6 ± 1.4 26.1 ± 1

Waist circumference (cm) 103.3 ± 2.7 103 ± 2.7 103.9 ± 2 102 ± 2 87 ± 4.3 88.1 ± 4

Systolic blood pressure (mm Hg) 122 ± 3.1 119 ± 2.5 123 ± 3 122.5 ± 2.9 j 109 ± 3.1 104 ± 4.2

Diastolic blood pressure (mm Hg) 77 ± 2.1 77.5 ± 1.6 81.5 ± 2.7 81 ± 2.6 75.5 ± 3 72 ± 2.9

FPG b (mmol/l) 6.26 ± 0.58 6.2 ± 0.4 5.7 ± 0.27 5.4 ± 0.2 4.6 ± 0.19 4.46 ± 0.14

Chol c (mmol/l) 5.7 ± 0.3 6.37 ± 0.3 i 5.5 ± 0.3 5.4 ± 0.3 4.5 ± 0.4 4.7 ± 0.4

TG d (mmol/l) 2.5 ± 0.24 2.8 ± 0.25 2.7 ± 0.2 2.75 ± 0.35 1.39 ± 0.25 1.14 ± 0.14

HDL e-c (mmol/l) 1.01 ± 0.03 1.09 ± 0.2 i 1.08 ± 0.05 1.07 ± 0.08 1.28 ± 0.09 1.48 ± 0.1

Insulin (pmol/l) 45.8 ± 12.3 38.1 ± 8.3 48.3 ± 11 51.8 ± 15.9 27 ± 7.2 29.8 ± 11.8

HOMA index f 1.8 ± 0.48 1.4 ± 0.32 1.7 ± 0.38 1.9 ± 0.7 0.88 ± 0.27 0.85 ± 0.28

Adiponectin (ng/ml) 87.7 ± 15 72.5 ± 14.2 91.9 ± 13.3 70.8 ± 8.8 56.5 ± 9.6 36.2 ± 6 k

IL6 g (pg/ml) 0.85 ± 0.4 0.61 ± 0.19 1.3 ± 0.49 1.13 ± 0.55 0.7 ± 0.2 1.3 ± 0.2

TNF α h (pg/ml) 1.66 ± 0.28 2.17 ± 0.4 2.35 ± 0.39 2.18 ± 0.5 1.89 ± 0.3 5.5 ± 0.8 k

a BMI: Body Mass Index, b FPG: Fasting Plasma Glucose, c Chol: Cholesterol, d TG: Triglycerides, e HDL: High Density Lipoprotein, f HOMA Index: Homeostasis Model Assessment Index, g IL6: Interleukin 6, h TNF α: Tumor Necrosis Factor α, i P < 0.05 for difference between baseline and after intervention in metabolic syndrome group, j P<0.05 for difference between baseline and after intervention in metabolic syndrome garlic group, k P < 0.05 for difference between baseline and after intervention in normal women garlic group

Table 1. Characteristics of the study population (Data are shown as Mean ± SE)

Int J Endocrinol Metab. 2010;8(2):68-73

70 Garlic, serum adiponectin and interleukin in metabolic syndromeSharifi F et al.

events were recorded. The participants were asked not to change their diet or physical activity during the study and to report any changes. The 300 mg tablets of garlic were manufactured (Amin pharmaceutical co., Isfahan, Iran) and matching placebo tablets were produced un- der standard manufacturing practice standards (Tehran University of Medical Sciences, Tehran, Iran). All study medication was labeled, and dispensed by the Valieasr Hospital endocrine clinic.

Measurements

Body weight was measured to the nearest 0.1 kg with a balanced beam scale, while wearing light clothing, and height was measured with a stadiometer to the nearest 0.5 cm. BMI was calculated based on the weight/height² formula. Waist circumference between the lowest rib and the iliac crest, at the level of umbilicus, was measured in duplicate to the nearest millimeter using flexible tape. Blood pressure was measured with the subject seated using a random zero sphygmo-manometer. Systolic (Ko- rotkoff phase I) and diastolic (Korotkoff phase V) blood pressure was measured twice on the left upper arm and the average of the two measurements was used for analy- sis.In all the women, blood samples were collected be- tween 8.00-9.00 AM, after at least 12 hours of fasting. The basal levels of adiponectin, insulin, interleukin 6 (IL6), tumor necrotizing factor α (TNF α) and plasma glucose were measured, and a lipid profile was also obtained. The Homeostasis Model Assessment Index (HOMA Index) was used to determine the level of insulin resistance and was calculated according to the following equation:

[Insulin (μU/mL)] [FPG (mmol/L)] /22.5. Insulin resis- tance was diagnosed in cases with a HOMA index of more than 2.1, (14).

Insulin levels were measured via an electrochemilu- minescence immunoassay (ECLIA) using commercially available kits (Roche, German), and adiponectin was measured using human adiponectin ELISA kits (Bioven- dor, Germany) with a limit of detection 7 ng/ml. Intra and inter-assay CV for the assay were 7 and 8 % in the lower limit and 6.4% and 7.3% for upper limit concentrations respectively. TNF-α was measured with the use of ELISA kits (Bender medsystem), with a sensitivity of 5pg/ml and inter and intra-assay CVs of 8.1 and 7.7% respectively. IL 6 was measured by ELISA kits (Bender medsystem). The sensitivity of the kit was 0.92 pg/mL. Inter and intra-assay CV for the kits were 5.2% and 3.4% respectively.

Statistical methods

Data are presented as Mean ± SE. Between group com- parisons of changes in lipid and adipokines parameters were done using one-way ANOVA. Mann-Whitney test was used for those variables without normal distribution. Within group assessments of changes in the parameters were analyzed by paired the t-test and Kruskal-Wallis Test. Significance of differences was evaluated using the SPSS

version 11.5 and defined at a 0.05 level of confidence.

Results

At the end of the study, of 50 subjects with MS, five in the garlic group and six in the placebo arm did not com- plete the study and were excluded. Of 12 normal subjects, who entered in the study, 10 completed it. All the exclud- ed subjects were followed by telephone. No complication with the medication was reported by the excluded sub- jects. One additional subject with MS entered later to the placebo arm of the study and finally the study popula- tion consisted of 50 subjects, 20 subjects with metabolic syndrome in the garlic group, 20 subjects with meta- bolic syndrome in the placebo group, and 10 normal subjects in the garlic group. No significant differences were observed in the baseline characteristics among the 3 groups. The adverse events reported in this study were mild and data showed a good compliance for the medica- tions. Clinical parameters and markers of inflammation at the 6 week assessment of women with metabolic syn- drome before and after intervention are shown in Table1.

Compared with placebo group, garlic treatment re- sulted in significantly lower weight (P = 0.04) and waist circumference (P < 0.001) in women with metabolic syndrome. No effect on weight (71.4 ± 3.8 Kg before treat- ment vs. 71.8 ± 4 Kg after treatment, p = 0.4) and waist circumference (87.8 ± 4.3 cm before treatment vs. 88± 4.4 cm after treatment, p = 0.4) was detected in normal sub- jects with garlic. None of the inflammatory biomarkers and plasma lipid levels showed significant differences between the garlic-treated and placebo groups with met- abolic syndrome (Table2).

While significant rise was seen in serum adiponectin concentration in normal subjects with garlic (56.5 ± 9.6 ng/ml after treatment vs. 36.2 ± 9.6 ng/ml before treat- ment, p = 0.024), no significant changes in other inflam- matory biomarkers or lipid concentrations were ob- served in normal subjects using garlic.

Discussion

This double blind placebo-controlled study demon- strated no effect of a 6-wk treatment with garlic tablets on plasma lipid concentrations of women with metabol- ic syndrome. Although a significant statistical reduction in weight and waist circumference was seen with garlic, the reduction was not clinically significant. The main finding of this study was that garlic has no detectable ef- fects on TNF-α, interleukin 6 and adiponectin concentra- tions in women with metabolic syndrome, which makes it unlikely that garlic exerts a beneficial effect on car- diovascular disease prevention by anti-inflammatory or lipid-lowering mechanisms. For a long time a preventive effect on atherogenesis has been considered for garlic because its lipid lowering properties. It has been shown that garlic inhibits enzymes involved in lipid synthesis, decreases platelet aggregation, and prevents lipid per-

Int J Endocrinol Metab. 2010;8(2):68-73

71Garlic, serum adiponectin and interleukin in metabolic syndrome Sharifi F et al.

Parameter (Mean ± SE a)

Average treatment effect (97.5% CI)

Garlic compared with placebo

Metabolic syndrome Placebo group (No. = 20)

Metabolic syndrome Garlic group (No. = 20)

% Change (97.5% CI of difference) p-value

Waist circumference (cm) (-1.2)-(0.6) (-2.4)-(-0.7) (-1.2)-(-0.1) 0.036

Systolic blood pressure (mmHg) (-5.4)-(1.4) (-3.7)-(2.7) (1.3) - (1.7) 0.5

Diastolic blood pressure (mmHg) (-3)-(5.8) (-5.5)- (5.7) (-2.5)-(-0.1) 0.7

FPG b (mmol/l) (-3.3)-(11.9) (-12.3) - (6.6) (-9)- (-5.3) 0.2

Chol c (mmol/l) (3.6)-(21.6) (-11.7) - (20.4) (-15.3)-(-0.8) 0.3

TG d (mmol/l) (-4.8)-(31.6) (-29)- (41) (-24.2)-(9.4) 0.6

HDL e (mmol/l) (0.12)-(16.8) (-14)-(17) (-14.1)-(0.2) 0.4

Insulin (pmol/l) (-22)-(208) (-17.6)-(63) 4.4-(-145) 0.2

Adiponectin (ng/ml) (-39.4)-(39.2) (-38)-(44.7) (1.4)-(5.5) 0.9

IL6 f (pg/ml) (-105.4)-(527) (-74.8)-(213) (30.6)-(-314) 0.3

TNF α g (pg/ml) (-49)-(168) (-55.7)-(100) (-6.7)-(-68) 0.5 a SE: Standard Error of mean, b FPG: Fasting Plasma Glucose, c Chol: Cholesterol, d TG: Triglycerides, e HDL: High Density Lipoprotein, f IL6: Interleukin 6, g TNF α: Tumor Necrosis Factor α

Table 2. Average treatment effects of placebo and garlic on clinical parameters and markers of inflammation at the 6-week assessment of women with meta- bolic syndrome

oxidation of oxidized erythrocytes and LDL (15, 16). How- ever, most clinical trials have indicated no reduction in total cholesterol with garlic and its effect on blood pres- sure and oxidative-stress reduction is controversial (17). The different results obtained in clinical trials may be due to usage of different garlic preparations with differ- ent dosage, selection of subjects, and duration of trials. Different garlic preparations have different properties. Some toxicity has been reported with raw garlic. Garlic powder must be prepared at a suitable temperature and is associated with some toxicity. No major studies on the efficacy of garlic oils have been reported (18). Aged garlic extracts (AGE) have increased sulfur compounds with the loss of allicin. There is also substantial variability in the contents of garlic preparations, with inadequate defini- tions of the biologically active and available constituents and their dissolution properties making it difficult to confirm the garlic in these trials. There is some evidence that higher garlic doses are associated with more signifi- cant effects. In the present study, we chose a relatively high dose of the garlic tablets (1.8 g/d, approximately equivalent to 9 mg allicin/d) to be able to detect the po- tentially beneficial effects of garlic. Measurement of gar- lic components plasma concentrations would have been helpful, but, unfortunately, these were not measured in our study. Our data are in agreement with many of the recent findings that did not observe any effects of garlic on plasma lipids (7, 8). To our knowledge, this is the first report for the effects of garlic on lipid concentrations in subjects with metabolic syndrome. Although a clini- cally significant rise in HDL-cholesterol was observed in normal women with garlic, this difference was not statistically significant. This result may be due to small sample size of normal women in our study. No signifi- cant changes in total cholesterol, triglyceride and low- density lipoprotein cholesterol (LDL-C) were observed in

normal women using garlic. Central obesity and conse- quent insulin resistance are major factors of metabolic syndrome and confer an increased risk of atherosclero- sis and cardiovascular disease (CVD). The possible role of inflammatory cytokines originating from adipose tissue in this process is still being elucidated. A growing body of evidence suggests that inflammatory processes play an important role in the pathophysiology of atheroscle- rosis (19-21). Substances like interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are indicators of oxidative stress and may play a role in promoting adverse vascular out- comes in the metabolic syndrome (9). Low levels of adi- ponectin and increased leptin also have been reported in this syndrome. Adiponectin is inversely associated with insulin resistance and inhibits inflammation. IL-6 is a cy- tokine that increases triglyceride formation and insulin resistance. Levels of IL-6 are linked to insulin resistance, adiposity (22), and the metabolic syndrome (23). TNF-α is produced mostly by fatty tissue, but also by macro- phages and endothelial cells. Its levels correlate with the amount of adiposity and have been linked to the increase in insulin resistance seen in obesity (24, 25). We chose adiponectin, IL-6 and TNF- α as primary outcomes of this study because of their possible effect on atherogenesis in the metabolic syndrome. Some in vitro studies indicated a reduced cytokine production in endothelial cells with high concentrations of garlic suggesting that it has anti- inflammatory properties (15, 26, 27).

Among limited number of clinical trials performed with garlic and different preparations of garlic, most evalu- ated the effect of garlic on glucose control, lipid profiles, hypertension and platelet aggregation (1, 7, 28, 29); only two clinical trials have been conducted to evaluate the ef- fect of garlic on inflammatory cytokines, and both have shown that garlic has no effect on these markers (30, 31). Of these, one study was performed in overweight smok-

Int J Endocrinol Metab. 2010;8(2):68-73

72 Garlic, serum adiponectin and interleukin in metabolic syndromeSharifi F et al.

er subjects, and the other in men with coronary artery disease; our results were in agreement with these two studies and revealed no significant changes in IL-6, TNF-α and adiponectin after a 6-week duration of treatment with garlic tablets, in women with metabolic syndrome. A rise in adiponectin concentration in normal women after garlic administration in this study may suggest a different effects of garlic in different health conditions, suggesting a preventive role for cardiovascular disease with garlic in healthy people. However considering the small sample size of normal subjects and lack of normal people on placebos in this study, any results in the nor- mal group should be interpreted cautiously.

In conclusion, our data demonstrated that a 6-week treatment with a high-dose, garlic tablets had no anti- inflammatory or lipid-lowering effect in women with metabolic syndrome. This suggests that short-time ad- ministration of garlic has no significant effect on the inflammatory processes associated with atherosclero- sis in a high risk population. Furthermore, increases in adiponectin levels in normal women with garlic showed that garlic tablets may have some anti-inflammatory ef- fects in healthy people, and may prevent cardiovascu- lar events in this group. More investigations with larger sample sizes and longer duration of interventions are recommended.

Financial support

This study was supported by Zanjan University of Medi- cal Sciences and was approved as the residency thesis of Dr. Behdad.

Conflict of interest

None declared.

Acknowledgement

We are grateful to Dr. Hamidi, Mr. Rahimi and to the laboratory staff for their assistance in this research.

References

1. Jain AK, Vargas R, Gotzkowsky S, McMahon FG. Can garlic reduce levels of serum lipids? A controlled clinical study. Am J Med. 1993;94(6):632-5.

2. Swiderski F, Dabrowska M, Rusaczonek A, Waszkiewicz-Robak B. Bioactive substances of garlic and their role in dietoprophylaxis and dietotherapy. Rocz Panstw Zakl Hig. 2007;58(1):41-6.

3. Vinson JA, Su X, Zubik L, Bose P. Phenol antioxidant quantity and quality in foods: fruits. J Agric Food Chem. 2001;49(11):5315-21.

4. Stevinson C, Pittler MH, Ernst E. Garlic for treating hypercho- lesterolemia. A meta-analysis of randomized clinical trials. Ann Intern Med. 2000;133(6):420-9.

5. Liu CT, Sheen LY, Lii CK. Does garlic have a role as an antidiabetic agent? Mol Nutr Food Res. 2007;51(11):1353-64.

6. Gorinstein S, Jastrzebski Z, Namiesnik J, Leontowicz H, Leontow- icz M, Trakhtenberg S. The atherosclerotic heart disease and pro- tecting properties of garlic: contemporary data. Mol Nutr Food Res. 2007;51(11):1365-81.

7. Superko HR, Krauss RM. Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-

density lipoprotein subclass distribution and lipoprotein(a). J Am Coll Cardiol. 2000;35(2):321-6.

8. Isaacsohn JL, Moser M, Stein EA, Dudley K, Davey JA, Liskov E, et al. Garlic powder and plasma lipids and lipoproteins: a multi- center, randomized, placebo-controlled trial. Arch Intern Med. 1998;158(11):1189-94.

9. Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr. 2006;136(3 Suppl):736S-40S.

10. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-607.

11. Rassoul F, Salvetter J, Reissig D, Schneider W, Thiery J, Richter V. The influence of garlic (Allium sativum) extract on interleukin 1alpha-induced expression of endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Phytomedicine. 2006;13(4):230-5.

12. Hodge G, Hodge S, Han P. Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel dis- ease. Cytometry. 2002;48(4):209-15.

13. Expert Panel on Detection E, Adults ToHBCi. Executive Summary of the Third Report of the National Cholesterol Education Pro- gram (NCEP) Expert Panel on Detection, Evaluation, and Treat- ment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97.

14. Meshkani R, Taghikhani M, Larijani B, Khatami S, Khoshbin E, Adeli K. The relationship between homeostasis model assess- ment and cardiovascular risk factors in Iranian subjects with normal fasting glucose and normal glucose tolerance. Clin Chim Acta. 2006;371(1-2):169-75.

15. Chang HS, Yamato O, Yamasaki M, Maede Y. Modulatory influ- ence of sodium 2-propenyl thiosulfate from garlic on cyclooxy- genase activity in canine platelets: possible mechanism for the anti-aggregatory effect. Prostaglandins Leukot Essent Fatty Acids. 2005;72(5):351-5.

16. Hasani-Ranjbar S, Larijani B, Abdollahi M. A systematic review of the potential herbal sources of future drugs effective in oxidant- related diseases. Inflamm Allergy Drug Targets. 2009;8(1):2-10.

17. Wu CC, Sheen LY, Chen HW, Tsai SJ, Lii CK. Effects of organosulfur compounds from garlic oil on the antioxidation system in rat liver and red blood cells. Food Chem Toxicol. 2001;39(6):563-9.

18. Banerjee SK, Mukherjee PK, Maulik SK. Garlic as an antioxidant: the good, the bad and the ugly. Phytother Res. 2003;17(2):97-106.

19. Hsueh WA, Quinones MJ. Role of endothelial dysfunction in in- sulin resistance. Am J Cardiol. 2003;92(4A):10J-7J.

20. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336(14):973-9.

21. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol lev- els in the prediction of first cardiovascular events. N Engl J Med. 2002;347(20):1557-65.

22. Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, et al. Elevated levels of interleukin 6 are reduced in serum and subcu- taneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab. 2000;85(9):3338-42.

23. Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, Pratley RE. Circulating interleukin-6 in relation to adiposity, insulin ac- tion, and insulin secretion. Obes Res. 2001;9(7):414-7.

24. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expres- sion of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87-91.

25. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tis- sue. Regulation by obesity, weight loss, and relationship to lipo- protein lipase. J Clin Invest. 1995;95(5):2111-9.

26. Moriguchi T, Takasugi N, Itakura Y. The effects of aged garlic extract on lipid peroxidation and the deformability of erythro- cytes. J Nutr. 2001;131(3s):1016S-9S.

27. Ide N, Lau BH. Garlic compounds minimize intracellular oxida- tive stress and inhibit nuclear factor-kappa b activation. J Nutr. 2001;131(3s):1020S-6S.

28. Duda G, Suliburska J, Pupek-Musialik D. Effects of short-term garlic supplementation on lipid metabolism and antioxidant

Int J Endocrinol Metab. 2010;8(2):68-73

73Garlic, serum adiponectin and interleukin in metabolic syndrome Sharifi F et al.

status in hypertensive adults. Pharmacol Rep. 2008;60(2):163-70. 29. Sobenin IA, Andrianova IV, Demidova ON, Gorchakova T, Orekhov

AN. Lipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-controlled randomized study. J Ath- eroscler Thromb. 2008;15(6):334-8.

30. van Doorn MB, Espirito Santo SM, Meijer P, Kamerling IM, Schoe-

maker RC, Dirsch V, et al. Effect of garlic powder on C-reactive protein and plasma lipids in overweight and smoking subjects. Am J Clin Nutr. 2006;84(6):1324-9.

31. Williams MJ, Sutherland WH, McCormick MP, Yeoman DJ, de Jong SA. Aged garlic extract improves endothelial function in men with coronary artery disease. Phytother Res. 2005;19(4):314-9.