The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis

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Contents lists available at ScienceDirect

Primary Care Diabetes journal homepage: http://www.elsevier.com/locate/pcd

Original research

The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis Ehsan Shabani a,∗, Korosh Sayemiri b, Mohammadtaghi Mohammadpour c a b c

MSc. Epidemiology Student Research Committee, Faculty of Health, Ilam University of Medical Sciences, Ilam, Iran Psychosocial Injuries Research Centre, Ilam University of Medical Sciences, Ilam, Iran MSc. Health Research Committee, Yasuj University of Medical Science, Yasuj, Iran

a r t i c l e

i n f o

a b s t r a c t

Article history:

Purpose: Several studies have been published about the effect of garlic on lipid profile and

Received 28 March 2018

blood glucose in diabetic patients. Which, the results mostly contradict with each other.

Received in revised form

This study aimed to investigate the effect of garlic on lipid profile and serum glucose levels

13 June 2018

in diabetic patients using a systematic review and meta-analysis.

Accepted 1 July 2018

Methods: This study was a systematic review and meta-analysis of articles published

Available online xxx

between 1988 and 2016. For this purpose, two independent researchers searched SID medical information databases including MagIran, Irandoc, Medlib, Iran Medex, Science Direct,

Keywords:

Scopus, Google and PubMed using keywords. Data were analyzed using STATA software.

Garlic

Results: After the initial search, 23,000 articles were found, of which 33 had the required

Lipid profile

criteria for the meta-analysis. In the present study, the total sample under review was 1273

Glucose parameters

individuals, with a mean of 39 samples per study. Overall, the garlic was more influential

Meta-analysis

than placebo in reducing the levels of lipid parameters including triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), and fasting blood sugar (FBS) and HbA1C . In the meta-analysis, the concentration of serum TC, LDL, TG, and HDL in the group receiving garlic compared with the placebo showed a significant decreased for 16.87 mg/dl (95% CI, −21.01, −12.73) (P = 0.001), 9.65 mg/dl (95% CI, −15.07, −4.23) (P = 0.001), 12.44 mg/dl (95% CI, −18.19, −6.69) (P = 0.001), and increased for 3.19 mg/dl (95% CI, 1.85, 4.53) (P = 0.001), respectively. Also, the concentration of serum FBS and HbA1C serum showed a significant decreased for 10.90 mg/dl (95% CI, −16.40, −5.40) (P = 0.001) and 0.60 mg/dl (95% CI, −0.98, −0.22) (P = 0.001), respectively. Conclusion: Garlic can reduce lipid profile as well as glucose parameters and be therapeutically effective in patients suffering from cardiovascular diseases and diabetes. © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

∗

Corresponding author at: Ilam University of Medical Sciences, Research Blvd, Ilam 6931975897, Iran. E-mail address: [email protected] (E. Shabani). https://doi.org/10.1016/j.pcd.2018.07.007 1751-9918/© 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

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1.

Introduction

Population with diabetes mellitus (DM) who have visited a doctor are increasing dramatically [1]. Diabetes affects over 140 million human population in the west and estimates of the prevalence will reach 300 million by 2025 [2]. Atherosclerosis is one of the late consequences of diabetes that affects many organs and is the cause of morbidity and mortality [3]. Elevated serum lipids are risk factors that cause atherosclerosis and progress diabetes particularly cardiovascular problems [4]. Hyperlipidemia causes atherosclerotic plaques and blocks artery in a chronic process. One percent Low Density Lipoprotein (LDL) reduction is associated with 2% decrease in the consequences of coronary artery disease. In addition, cholesterol-lowering drugs can reduce 25% LDL level in men with coronary artery disease and reduce subsequent mortality due to coronary heart disease [5]. High blood sugar causes non-enzymatic binding of glucose to proteins inside and outside the cell. Those who have DM will face long-term problems such as renal failure, eye damage, cardiovascular system failure and the central nervous system failure [6]. Among the currently therapeutic options, such as hypoglycemic drugs and insulin therapy, which have limitations, there has been much attention to use of traditional plants medicine that modulate hyperglycemia, dyslipidemia and prevent diabetes-induced complication. Also, plant-based medicine provides beneficial effects, alongside with only minimal or no complications in clinical experiments, and compared to other medicine are relatively cost effective. In this regard. Garlic beneficial effects such as antimicrobial and lowering blood fats have been proven in various studies that is among the herbs with a high consumption from the earliest times [7]. In another study, garlic is seen as an effective plant for blood glucose control through herbal therapy [8]. Researchers believe that the therapeutic effect of garlic and its components on modulating lipid synthesis and excretion of sterols is probably due to the Diallyl disulfide (DADS) decomposition of Allicin. Garlic decreases the absorption of cholesterol and inhibits the activity of enzymes involved in cholesterol synthesis [9–11]. Garlic is a member of the Liliaceae family. Garlic contains various compounds, including organic sulfur compounds, amino acids, vitamins and minerals. Probably, some components of garlic such as Allicin, aigio, S-allyl cysteine, and DADS have the therapeutic effects on serum levels of glucose, lipid profile and insulin [12]. According to the International Diabetes Federation (IDF), in 2030 the global prevalence of diabetes was approximately 439 million people and 7.7% of the word population [13]. Hence, the present study aimed to investigate the effect of garlic on lipid parameters and serum glucose levels in diabetic patients in order to achieve a comprehensive result through a systematic review and meta-analysis.

2.

Method

This study was a systematic review and meta-analysis considering the effect of garlic on serum lipid profile in diabetic

patients conducted on Persian and English-language articles published until the end of 2016. Two independent researchers searched SID medical information databases, Mag Iran, Iran doc, Med lib, Iran Med ex, Science Direct, Scopus, Google and Pub Med using articles’ keyword search strategy through keywords of garlic, serum lipids, glucose, meta-analysis and their derivatives and assessing their correlation with these key words of TC; HDL; TG; LDL; HbA1C and FBS in all related papers published in Farsi and English from 1988 to 2016. References used in all the articles that were found during the search were evaluated so that other possible sources might be also included in the study. Next; the study abstracts were reviewed and the one completely unrelated to the research question of this study were excluded. The full text of studies closely related or possibly related to the study were recorded and articles closely related to the aims of this study were selected. Finally; the selected articles were reviewed based on critical evaluation and articles that had the inclusion criteria were selected. It should be noted that all stages of the articles’ quality assessment were performed by two independent researchers. Inclusion criteria was: availability the full text article in English and Persian; patients with dyslipidemia with TC > 200 mg/dl; LDL > 130 mg/dl; HDL < 40 mg/dl and TG > 150 mg/dl and diabetic patients with fasting blood glucose >126 mg/dl; 2 h post prandial glucose (2HPP) > 200 mg/dl; not being in special groups; sufficient sample size; and the result of studies based on mean ± standard deviation (SD). Exclusion criteria included healthy people; smokers; pregnancies at risk of eclampsia and pre-eclampsia; people with gastrointestinal disorders (GI); and compound products (garlic + drug).

2.1.

Data extraction

Data were extracted based on the questionnaire using a checklist that contained information such as the type of study, year of study, age, gender, location, sample size, garlic dose, duration of garlic consumption, and average TC, HDL, TG, LDL, HBA1C, FBS serum.

2.2.

Statistical analysis

The studies’ distribution was conducted on the basis of the weighted average. Random-effects model meta-analysis was used to combine results. Plot Forest method was used for drawing figures; I2 index, Cochran test for estimating heterogeneity between studies, and funnel chart for detecting publication bias. Data were analyzed using the STATA software. In the heterogeneity test, P < 0.05 was considered as significant.

3.

Results

In the present study, 23,000 papers were selected after the initial search in the medical information databases. After reviewing the titles and abstracts by two independent researchers, 21,725 articles unrelated to the subject of our study were excluded. Finally, the full text of 1275 articles was

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

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Table 1 – The characteristics of the collected data in the present meta-analysis. Study

Type study

SampleN Gender (M/F) garlic/placebo

Ebadi et al. [36] Emami et al. [37] Khademian-Ravandi et al. [38] Khademian-Ravandi et al. [39] Parastouei et al. [40] Zekri et al. [41] Mahmoodi et al. [42] Mahmoodi et al. [43] Mahmoudi et al. [44] Bashiri et al. [45] Aslani et al. [46] Jabbari et al. [47] Harenberg et al. [48] Durak et al. [49] Irshad et al. [50] Lachhiramka et al. [51] Gardner et al. [52] Sobenin et al. [53] Hussien et al. [54] Adler et al. [55] Ashraf et al. [56] Byrne et al. [57] Jung et al. [58] Seo et al. [59] Ho et al. [60] McCrindle et al. [61] Study

Clinical trials Clinical trials Clinical trials Clinical trials Semi experintalme Clinical trials Clinical trials Clinical trials Semi experintalme RCT Crossover Crossover Clinical trials Clinical trials Clinical trials Clinical trials Clinical trials Clinical trials RCT-DB Clinical trials RCT RCT-DB RCT Parallel RCT-DB RCT Type study

60 50 40 50 20 30 25 30 18 55 25 25 20 23 100 50 60 51 40 20 23 42 70 31 55 14 SampleN

Superko et al. [62] Tahbaz et al. [63] Scicali et al. [64] Sahebkar et al. [65] Sahebkar et al. [66] Cicero et al. [67] Bordia et al. [35]

Parallel RCT-DB Parallel RCT-DB RCT-DB Crossover Clinical trials

20 30 21 41 50 24 60

9/21/9/21 Not stated M/F: 24/16 M/F: 11/39 M:20 M/F: 13/17 M/F: 7/18 M/F: 11/19 M: 18 27/28 Not stated Not stated Not stated 14/9 Not stated 30/20 Not stated Not stated 8/12/10/10 M:20 M: 12/11 11/9/8/14 15/20/17/18 Not stated 10/18/7/20 F: 8/6 Gender (M/F) garlic/placebo Not stated M/F: 16/14 Not stated 7/13/12/9 Not stated 13/11/13/11 8/22/14/16

evaluated and if the paper under review had the inclusion criteria, the required data would be extracted. 1157 article were excluded at this stage. After screening the full articles and their abstracts, 118 articles remained and then 85 other studies were excluded. Ultimately, 33 studies which met the inclusion criteria were selected (Tables 1–3). The final papers had been conducted between the years 1988 and 2016 with a total sample of 1273 people and an average of 39 samples per study. Duration of the intervention period for the studies included in the meta-analysis was 2–180 days from 500 to 20,000 mg dose of garlic. All studies were reviewed in each stage by two independent researchers. In case of disagreement, a third reviewer would review the study to make a decision (Fig. 1). In the present study, the effect of garlic on lipid parameters such as TC, HDL, LDL, TG, and FBS was significant, which is shown in Figs. 2–7, respectively. Generally, garlic reduced serum cholesterol levels compared to the placebo group for 16.87 mg/dl (95% CI, −21.01, −12.73) and this relationship was statistically significant (P = 0.001) (Fig. 2). Random-effects model was used due to the level of heterogeneity between studies (I2 = 96.2%). TG is another serum lipid indicator that garlic reduced compared to the placebo group for 12.44 mg/dl (95% CI, −18.19, −6.69)

Age Not stated 20–60 30–65 44–66 22–26 36–54 44–49 36–48 20–30 30–60 36–43 36–43 36–71 24–68 Not stated 40–60 Not stated 30–65 34–62 Not stated 34–57 40–64 53–65 Not stated 41–59 49–60 Age 21–60 8–18 21–60 18–65 43–63 42–57 43–49

Dose garlic (mg/day)

Duration garlic (day)

1203 1200 900 900 700 10,000 10,000 10,000 1000 20,000 1000 1000 600 10,000 500 3000 4000 1000 600 1000 900 900 600 900 6000 80 Dose garlic (mg/day) 1080 900 1080 7800 900 20,000 2400

60 90 28 42 14 42 42 42 28 56 60 60 28 120 90 90 90 84 28 84 84 84 84 180 84 84 Duration garlic (day) 91 56 91 77 84 2 90

Year 2005 2015 2004 2004 2012 2011 2005 2011 2014 2016 2005 2005 1988 2004 2016 2016 1998 2001 2007 2013 1995 1992 2005 1999 2013 2012 Year 2016 1998 2016 1997 1999 2006 2005

and this relationship was also significant (P = 0.001) (Fig. 5). Random-effects model was used due to the level of heterogeneity between studies (I2 = 93.6%). Also, garlic reduced glucose parameters such as FBS versus placebo group for 10.90 mg/dl (95% CI, −16.40, −5.40) and this relationship was significant (P = 0.001) (Fig. 6). Random-effects model was used due to heterogeneity between studies (I2 = 94.9%). The other serum glucose indicator assessed in the meta-analysis was HbA1c that garlic reduced compared to the placebo group for 0.60 mg/dl (95% CI, −0.98, −0.22) and the relationship was significant (P = 0.001) (Fig. 7). Here, a random-effects model was also used due to heterogeneity between studies (I2 = 93.2%). Figures indicated the impact of garlic on lipid profiles and glucose parameters in general and separately for all studies and the 95% CI in studies under review based on year, author name and random effects model. The midpoint of each segment showed the impact of garlic on lipid profiles and glucose parameters in each study. Segments showed 95% CI per study. Rhombus shape indicated the overall result and squares’ given weight outcome with its confidence interval (horizontal diameter diamond) for all studies. Moreover, Inverted funnel plot results showed that low risk of

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

Emami et al. [37]

Khademian-Ravandi et al. [38]

Khademian-Ravandi et al. [39]

Parastouei et al. [40]

Zekri et al. [41]

Mahmoodi et al. [42]

Mahmoodi et al. [43]

Mahmoudi et al. [44]

Bashiri et al. [45]

Aslani et al. [46]

Jabbari et al. [47]

Harenberg et al. [48]

Harenberg et al. [48]

Harenberg et al. [48]

−29.30 (−49.08, −9.52) −14.66 (−37.12, 7.80) −18.60 (−35.71, −1.49) −14.96 (−31.63, 1.71) −5.14 (−13.89, 3.61) −12.50 (−14.91, −10.09) −20.56 (−24.05, −17.07) −29.60 (−47.64, −11.56) −9.11 (−31.44, 13.22) −19.10 (−32.34, −5.86) −9.80 (−29.41, 9.81) −0.10 (−21.39, 21.19) −19.60 (−46.23, 7.03) −19.60 (−46.23, 7.03) −19.60 (−46.23, 7.03)

LDL

1.00 (−3.64, 5.64) 2.04 (−4.49, 8.57) 1.50 (−2.75, 5.75) 3.31 (−0.14, 6.76) 5.99 (3.79, 8.19)

3.00 (−2.78, 8.78) 3.80 (−0.48, 8.08) −1.20 (−7.47, 5.07) −1.40 (−7.51, 4.71) Not stated

−23.40 (−40.95, −5.5) 0.35 (−15.69, 16.39 −15.70 (−32.94, 1.54) −2.80 (−9.18, 3.58) −2.80 (−9.18, 3.58 0.70 (−0.52, 1.92) −3.38 (−6.24, −0.52) −2.50 (−3.87, −1.13) −7.67 (−25.72, 10.38) −14.80 (−28.12, −1.48) −0.30 (−19.15, 18.55) −0.80 (−17.88, 16.28) Not stated

Not stated

Not stated

1.90 (1.42, 2.38) 1.10 (0.31, 1.89) 4.10 (3.47, 4.73)

TG

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HDL

p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

TC

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˙1 −X ˙ 2 (95%CI)) Experimental(X

Study

4

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

Table 2 – Effect of garlic on lipid profile and blood glucose. ˙ 2 (95%/CI)) ˙1 −X Control(X FBS

HBA1C

TC

HDL

LDL

TG

FBS

−0.84 (−43.63, 41.95) −3.46 (−39.88, 32.96) 4.20 (−38.37, 46.77) 19.42 (−33.87, 72.71) −9.17 (−12.18, −6.16) −9.00 (−13.79, −4.21) 8.20 (−2.50, 18.90) −37.70 (−46.77, −28.63) −10.38 (−67.55, 46.79) −33.90 (−93.57, 25.77) −20.90 (−74.22, 32.42) 8.80 (−44.62, 62.22) Not stated-

Not stated

Not stated

−8.40 (−19.48, 2.68) −3.48 (−17.47, 10.41) Not stated

−4.17 (−32.62, 24.28) −26.60 (−56.09, 2.89) Not stated

Not stated

−1.33 (−1.96, −0.70) Not stated

0.50 (−4.57, 5.57) −1.76 (−7.44, 3.92) Not stated

Not stated

−14.66 (−37.12, 7.80) −7.00 (−20.74, 6.74) −12.65 (−34.94, 9.64) Not stated

−11.20 (−30.10, 7.70) −5.20 (−23.79, 13.39) Not stated

5.40 (−18.09, 28.89) Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

−0.99 (−6.75, 4.77) Not stated

−1.11 (−6.42, 4.20) Not stated

Not stated

−0.40 (−0.50, −0.30) −0.30 (−13.63, 13.03) 0.03 (−0.03, 0.09) Not stated

0.81 (−1.71, 3.33) Not stated

Not stated

−9.77 (−13.36, −6.18) −18.10 (−24.50, −11.70) −6.70 (−7.77, −5.63) Not stated

−3.46 (−13.31, 6.39) Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

−0.78 (−30.71, 29.15) 15.50 (−9.89, 40.89) Not stated

Not stated

Not stated

2.93 (−6.99, 12.85) 8.00 (−2.80, 18.80) Not stated

Not stated

Not stated

−0.22 (−7.51, 7.07) −0.10 (−3.86, 3.66) Not stated

Not stated

Not stated

2.45 (−13.19, 18.09) 4.10 (−4.63, 12.83) Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated-

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated-

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

0.00 (−1.18, 1.18) Not stated

HBA1C

Not stated

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˙1 −X ˙ 2 (95%CI)) Experimental(X

Study TC Durak et al. [49]

Irshad et al. [50]

Gardner et al. [52]

Sobenin et al. [53]

Harenberg et al. [48]

Hussien et al. [54]

Adler et al. [55]

Ashraf et al. [56]

Byrne et al. [57]

Jung et al. [58]

Seo et al. [59]

HDL

LDL

TG

FBS

HBA1C

TC

HDL

LDL

TG

FBS

10.83 (7.58, 14.08) 2.56 (1.13, 3.99)

−57.23 (−82.31, −32.15) −21.51 (−31.80, −11.22) Not stated

−28.62 (−38.86, −18.38) −23.79 (−42.75, −4.83) Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

−50.50 (−73.55, −27.45) Not stated

−1.43 (−2.03, −0.83 Not stated

−12.50 (−19.57, −5.43) Not stated

0.70 (−0.56, 1.96) Not stated

−7.55 (−16.68, 1.58) Not stated

−7.71 (−22.30, 6.88) Not stated

Not stated

Not stated

Not stated

Not stated

9.00 (8.26, 9.74)

Not stated

4.00 (2.40, 5.60)

Not stated

2.80 (1.45, 4.15)

Not stated

Not stated

Not stated

2.00 (−15.93, 19.93) Not stated

Not stated

Not stated

0.00 (−10.61, 10.61) Not stated

Not stated

Not stated

0.10 (−1.20, 1.40) 2.00 (−3.17, 7.17) Not stated

Not stated

−10.00 (−23.93, 3.93) Not stated

−4.60 (−8.67, −0.53) 3.00 (−9.22, 15.22) Not stated

Not stated

3.00 (−6.03, 12.03) Not stated

−19.80 (−22.36, −17.24) −7.00 (−44.45, 30.45 Not stated-

Not stated

Not stated

0.38 (−2.25, 3.01) 10.81 (8.89, 12.73) 1.16 (−1.81, 4.13) −1.00 (−8.75, 6.75) 3.35 (2.63, 4.07)

10.04 (1.79, 18.29) −29.33 (−55.17, −3.49) −23.93 (−38.45, −9.41) −20.00 (−44.86, 4.86) −30.15 (−32.32, −27.98) −7.72 (−22.81, 7.37)

−54.04 (−66.24, −41.84) Not stated

Not stated

−6.18 (−15.58, 3.32) Not stated

1.55 (−1.12, 4.22 Not stated

−4.24 (−12.26, 3.78) Not stated

−8.10 (−23.09, 6.89) Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

−1.00 (−5.76, 3.76) Not stated

Not stated

Not stated

−0.39 (−38.23, 37.45) 4.00 (−43.95, 51.95) −2.02 (−4.07, 0.03) Not stated

Not stated

Not stated

−2.32 (−22.52, 17.88) −6.00 (−23.63. 11.63) −2.70 (−4.32, −1.08) 0.00 (−21.16, 21.16)

Not stated

Not stated

2.31 (−5.84, 10.46) 1.00 (−8.20, 10.20) Not stated

Not stated

Not stated

1.16 (−19.48, 21.80) −2.00 (−20.67, 16.67) −2.11 (−3.37, −0.85) 1.93 (−20.12, 23.98)

Not stated

Not stated

Not stated

0.38 (−6.45, 7.21)

−40.91 (−50.52, −31.30) −25.09 (−25.77, −24.41) −5.01 (−30.36, 20.34) 14.00 (−37.78, 65.78) 1.42 (−2.57, 5.41) Not stated

Not stated

4.64 (−5.04, 14.32)

HBA1C

Not stated

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Lachhiramaka et al. [51]

−67.28 (−100.40, −34.16) −23.62 (−35.08, −12.16) −30.89 (−36.99, −24.78) −32.40 (−35.82, −28.98) −10.00 (−27.38, 7.38) −19.60 (−46.23, 7.03) −7.34 (−15.85, 1.17) −30.10 (−30.63, −29.57 −28.95 (−48.80, −9.09) −15.00 (−38.29, 8.29) −27.23 (−29.48, −24.98) −11.58 (−29.09, 5.93)

˙1 −X ˙ 2 (95%/CI)) Control(X

p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

5

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

– Table 2 (Continued)

6

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– Table 2 (Continued) ˙1 −X ˙ 2 (95%CI)) Experimental(X

Study

˙1 −X ˙ 2 (95%/CI)) Control(X

TC

HDL

LDL

TG

FBS

HBA1C

TC

HDL

LDL

TG

FBS

0.38 (−6.45, 7.21) 3.50 (−1.28, 8.28) 0.30 (−15.68, 16.28) 8.88 (−12.37, 30.13) 0.00 (−6.48, 6.48) 1.54 (−17.23, 20.32) 0.00 (−5.26, 5.26) 0.10 (−4.80, 5.00) Not stated

−7.72 (−22.81, 7.37) 5.11 (−4.55, 14.77) −15.00 (−40.25, 10.25) 3.87 (−14.79, 22.53) 10.00 (−31.17, 51.17) 2.70 (−10.35, 15.75 0.00 (−19.14, 19.14) Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

−10.04 (−23.71, 3.63) Not stated

Not stated

4.00 (−17.20, 25.20) 37.60 (6.41, 68.79) Not stated

Not stated

Not stated

0.00 (−21.16, 21.16) 6.22 (−6.49, 18.93) 5.00 (−26.25, 36.25) Not stated

Not stated

Not stated

4.64 (−5.04, 14.32) −0.33 (−5.39, 4.73) −2.20 (−15.14, 10.74) Not stated

Not stated

−19.58 (−50.62, 11.46) −18.20 (−49.20, 12.80) −8.88 (−27.67, 9.91) −11.00 (−39.95, 17.95) −0.39 (−11.26, 10.48) 0.00 (−8.61,8.61)

1.93 (−20.12, 23.98) −61.60 (−76.00, −47.20) 18.00 (−25.38, 61.38) Not stated

Not stated

Not stated

−10.00 (−49.02, 29.02) Not stated

10.00 (−25.51, 45.51) Not stated

Not stated

Not stated

0.00 (−5.38, 5.38) Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

3.20 (−3.96, 10.36) Not stated

−21.50 (−46.23, 3.23) Not stated

0.00 (−12.89, 12.89) Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

Not stated

31.60 (25.44, 37.76) Not stated

Not stated

Bordia et al. [35]

−4.00 (−8.45, 0.45) Not stated

0.77 (−5.54, 7.08) −0.20 (−5.45, 5.05) Not stated

Not stated

Not stated

0.00 (−17.55, 17.55 −1.20 (−10.35, 7.95) Not stated

Not stated

4.30 (−17.24, 25.84) Not stated

8.49 (−4.36, 21.34) 0.00 (−9.57, 9.57) Not stated

−8.00 (−49.17, 33.17) Not stated

Cicero et al. [67]

−11.58 (−29.09, 5.93) −7.57 (−20.30, 5.16) −20.00 (−54.84, 14.84) 6.18 (−14.29, 26.64) 11.00 (−32.31, 54.31) 3.09 (−17.51, 23.69) 0.00 (−21.53, (−21.53 2.50 (−8.91, 13.91) Not stated

Ho et al. [60]

−7.57 (−20.30, 5.16) −20.00 (−54.84, 14.84) 6.18 (−14.29, 26.64)

3.50 (−1.28, 8.28) 0.30 (−15.68, 16.28) 8.88 (−12.37, 30.13)

5.11 (−4.55, 14.77) −15.00 (−40.25, 10.25) 3.87 (−14.79, 22.53)

−19.58 (−50.62, 11.46) −18.20 (−49.20, 12.80) −8.88 (−27.67, 9.91)

−61.60 (−76.00, −47.20) 18.00 (−25.38, 61.38) Not stated

−0.33 (−5.39, 4.73) −2.20 (−15.14, 10.74) Not stated

6.22 (−6.49, 18.93) 5.00 (−26.25, 36.25) Not stated

4.00 (−17.20, 25.20) 37.60 (6.41, 68.79) Not stated

Seo et al. [59]

Ho et al. [60]

McCrindle et al. [61]

Superko et al. [62]

Tahbaz et al. [63]

Scicali et al. [64]

Sahebkar et al. [65]

Sahebkar et al. [66]

McCrindle et al. [61]

Superko et al. [62]

Not stated

Not stated

Not stated

Not stated

−1.50 (−3.74, 0.74) Not stated

Not stated

Not stated

−10.04 (−23.71, 3.63)

Not stated

HBA1C

Not stated

Not stated

−0.20 (−1.16, 0.76) Not stated

Not stated

Not stated

Not stated

Not stated

ARTICLE IN PRESS

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−0.20 (−1.16, 0.76) 8.19 (−3.45, 19.83)

Abstracts and full articles screened (n = 118)

Arcles excluded (1157): No text found (n = 192) Non-related articles (n = 697) Non-clinical trials (n = 219) Combination products (n = 18) Unrelated indications (n = 31)

Articles excluded (n = 85) Trials included (n = 33)

−1.87 (−5.00, 1.27)

TG TC

−2.19 (−3.59, −0.79) 0.5 (−0.22, 1.23 −5.71 (−10.51, −0.92) −0.60 (−0.98, −0.22) −10.90 (−16.40, −5.40) −12.44 (−18.19, −6.69) −9.65 (−15.07, −4.23) 3.19 (1.85, 4.53 −16.87 (−21.01, −12.73)

LDL TC HBA1C FBS TG HDL Overall

LDL

Experimental (WMD(95%CI)) Study

Table 3 – The overall result of the effect of garlic on lipid profile and blood glucose.

1275 Citations

Fig. 1 – Flowchart of selecting the studies to be included in the present meta-analysis.

HDL

Control (WMD (95%/CI))

FBS

HBA1C

p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

publication bias may exist in outcomes of blood liquids for TC, TG, HDL, and LDL. For blood glucose outcomes, moderate risk of publication bias may exist in HbA1c.

4.

Discussion

In current systematic review, several papers were identified during the search process. After reviewing the titles, abstracts and various variable of articles, they were included into the checklists. After the final evaluation, 33 full text articles were provided for the researchers, that had been carried out between 1988 and 2016 with a total sample of 1273 individuals. Due to the high heterogeneity of findings, random effects model was used in all following stages. According to this model, it is assumed that the observed differences are due to different sampling as well as differences in measured variables in different studies. This study aimed to investigate the effect of garlic on lipid parameters and serum glucose in patients with diabetes through a meta-analysis performed on 33 experimental studies. Duration of the intervention period for the studies included in the meta-analysis was 2–180 days from 500 to 20,000 mg dose of garlic. The results showed that garlic has beneficial effect on lipid profile parameters and serum glucose and their association was statistically significant (P = 0.001). In various studies, the effective components of various forms of garlic are mentioned. The major components of garlic include allyne and the enzyme alinaz. Garlic powder contains three active substances of alin, alkaline, and allicin. The old garlic has an abundance of antioxidant compounds, including alixin and selenium [14–16]. In Bordia et al. study, 62 diabetic patients with cardiovascular disease who had high serum cholesterol levels were treated with garlic for 10 months and total serum cholesterol, triglycerides and LDL cholesterol significantly decreased while HDL cholesterol increased significantly [17] and the present study also showed it. Mansell et al. studied 60 patients with type 2 diabetes, in which patients received 900 mg garlic tablets daily and TC and LDL cholesterol reduced after 6 weeks and HDL cholesterol significantly increased after 12 weeks, but there was no change in serum triglycerides [18]. However, TG did not decrease in present study that may be

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

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p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

Study ID

WMD (95% CI)

Iran Emami F (2005) Khademianravandi R (2014) AfkhamiArdakani M (2003) Parastoi K (2004) Zekri R (2012) Mahmoodi M (2011) Mahmoodi M (2005) Mahmoodi M (2011) Bashiri J (2014) Jabbari A (2005) Jabbari A (2005) Aslani N (2013) Subtotal (I-squared = 58.0%, p = 0.006) . Irland Harenberg J (1988) Subtotal (I-squared = .%, p = .) . Turkey ILKer D (2003) Subtotal (I-squared = .%, p = .) . India Yadav K (2016) Lachhiramka P (2016) Bordia A (1997) Xiao-Hua Z (1997) Subtotal (I-squared = 70.6%, p = 0.017) . USA Gardner Christopher D (2000) Robersuperko H (1999) Subtotal (I-squared = 28.0%, p = 0.239) . Aragh Zuhair M (2013) Subtotal (I-squared = .%, p = .) . Canada Brian W (1998) Adam JA (1995) Subtotal (I-squared = 63.0%, p = 0.100) . Islamabad Rizwan A (2005) Subtotal (I-squared = .%, p = .) . Germany Adeshk J (1992) Subtotal (I-squared = .%, p = .) . England Byrn DJ (1999) Subtotal (I-squared = .%, p = .) . Russia Sobenin I (2007) Subtotal (I-squared = .%, p = .) . Syngapor Xing Lin Ho (2016) Xing Lin Ho (2016) Subtotal (I-squared = 0.0%, p = 0.835) . Korea Eun-Soo Jung M.S (2013) Dae Yun Seo (2012) Subtotal (I-squared = 0.0%, p = 0.511) . Overall (I-squared = 92.2%, p = 0.000) NOTE: Weights are from random effects analysis -100

% Weight

-29.30 (-49.08, -9.52) 2.49 -14.66 (-37.12, 7.80) 2.14 -18.60 (-35.71, -1.49) 2.90 -14.96 (-31.63, 1.71) 2.98 4.58 -5.14 (-13.89, 3.61) -12.50 (-14.91, -10.09) 5.64 -20.56 (-24.05, -17.07) 5.52 -29.60 (-47.64, -11.56) 2.75 -9.11 (-31.44, 13.22) 2.15 2.51 -9.80 (-29.41, 9.81) -0.10 (-21.39, 21.19) 2.28 -19.10 (-32.34, -5.86) 3.62 -15.21 (-19.80, -10.61) 39.55 -19.60 (-46.23, 7.03) -19.60 (-46.23, 7.03)

1.70 1.70

-67.28 (-100.40, -34.16)1.23 -67.28 (-100.40, -34.16)1.23 -23.62 (-35.08, -12.16) 3.99 -30.89 (-36.99, -24.78) 5.11 -32.40 (-35.82, -28.98) 5.53 0.00 (-21.53, 21.53) 2.25 -27.17 (-34.49, -19.85) 16.88 -10.00 (-27.38, 7.38) 2.50 (-8.91, 13.91) -1.96 (-13.70, 9.78)

2.86 4.00 6.86

-30.10 (-30.63, -29.57) 5.75 -30.10 (-30.63, -29.57) 5.75 11.00 (-32.31, 54.31) 0.79 -28.95 (-48.80, -9.09) 2.47 -13.80 (-51.79, 24.19) 3.26 -27.23 (-29.48, -24.98) 5.65 -27.23 (-29.48, -24.98) 5.65 -15.00 (-38.29, 8.29) -15.00 (-38.29, 8.29)

2.04 2.04

-11.58 (-29.09, 5.93) -11.58 (-29.09, 5.93)

2.83 2.83

-7.34 (-15.85, 1.17) -7.34 (-15.85, 1.17)

4.63 4.63

3.09 (-17.51, 23.69) 6.18 (-14.29, 26.64) 4.64 (-9.88, 19.16)

2.37 2.39 4.76

3.72 -7.57 (-20.30, 5.16) -20.00 (-54.84, 14.84) 1.13 4.86 -9.03 (-20.99, 2.92) -16.87 (-21.01, -12.73) 100.00

0

100

Fig. 2 – Forest plot results of the effects of garlic on serum TC levels (mg/dl). The black squares represent individual studies and the size of the square represents the weight given to each study in the meta-analysis. The diamond represents the pooled estimate and the horizontal line represents the 95% confidence interval.

due to the type of consumed garlic. In another study conducted by Rahmani, cholesterol level and LDL-C decreased by prescribing garlic powder for 12 weeks [19]. In the study of Morcos, garlic and fish oil dietary supplementations for a month lead to lower cholesterol, triglyceride, LDL-C but increase in HDL-C [20]. Zhang et al. carried out an study and showed that garlic oil leads to more HDL and serum glucose in women [21]. Slowing et al. evaluate low-cholesterol diet on rats and found that garlic consumption decreased LDL-C

cholesterol [22]. In comparison to the results of this study, it is concluded that the results of their study are consistent with ours, and differences in some studies can be linked to the type and duration of the study. Lee et al. examined 20 male rats for 5 weeks with daily garlic combined to high-fat diet, their result showed significantly lower TG and LDLc levels in the the experimental group compared to the controls and increased HDLc [23]. In another study, Jain et al. examined 42 patients with total serum cholesterol of ≤220 mg/dl,

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

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p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

Study ID Iran Emami F (2005) Khademianravandi R (2014) AfkhamiArdakani M (2003) Parastoi K (2004) Zekri R (2012) Mahmoodi M (2011) Mahmoodi M (2005) Mahmoodi M (2011) Bashiri J (2014) Jabbari A (2005) Jabbari A (2005) Aslani N (2013) Subtotal (I-squared = 80.5%, p = 0.000) . Turkey ILKer D (2003) Subtotal (I-squared = .%, p = .) . India Yadav K (2016) Bordia A (1997) Xiao-Hua Z (1997) Subtotal (I-squared = 97.1%, p = 0.000) . USA Gardner Christopher D (2000) Robersuperko H (1999) Subtotal (I-squared = 0.0%, p = 0.580) . Aragh Zuhair M (2013) Subtotal (I-squared = .%, p = .) . Canada Brian W (1998) Adam JA (1995) Subtotal (I-squared = 0.0%, p = 0.750) . Islamabad Rizwan A (2005) Subtotal (I-squared = .%, p = .) . Germany Adeshk J (1992) Subtotal (I-squared = .%, p = .) . England Byrn DJ (1999) Subtotal (I-squared = .%, p = .) . Russia Sobenin I (2007) Subtotal (I-squared = .%, p = .) . Syngapor Xing Lin Ho (2016) Xing Lin Ho (2016) Subtotal (I-squared = 0.0%, p = 0.612) . Korea Eun-Soo Jung M.S (2013) Dae Yun Seo (2012) Subtotal (I-squared = 0.0%, p = 0.707) . Overall (I-squared = 93.0%, p = 0.000) NOTE: Weights are from random effects analysis -30.1

WMD (95% CI)

% Weight

1.00 (-3.64, 5.64) 2.04 (-4.49, 8.57) 1.50 (-2.75, 5.75) 3.31 (-0.14, 6.76) 5.99 (3.79, 8.19) 1.90 (1.42, 2.38) 1.10 (0.31, 1.89) 4.10 (3.47, 4.73) 3.00 (-2.78, 8.78) -1.20 (-7.47, 5.07) -1.40 (-7.51, 4.71) 3.80 (-0.48, 8.08) 2.60 (1.41, 3.80)

3.35 2.41 3.58 4.08 4.87 5.56 5.50 5.54 2.74 2.51 2.59 3.56 46.30

10.83 (7.58, 14.08) 4.21 10.83 (7.58, 14.08) 4.21 2.56 (1.13, 3.99) 9.00 (8.26, 9.74) 0.00 (-5.26, 5.26) 4.21 (-1.26, 9.68)

5.27 5.51 3.00 13.78

3.00 (-6.03, 12.03) 1.58 0.10 (-4.80, 5.00) 3.20 0.76 (-3.55, 5.07) 4.78 10.81 (8.89, 12.73) 5.02 10.81 (8.89, 12.73) 5.02 0.00 (-6.48, 6.48) 1.16 (-1.81, 4.13) 0.96 (-1.74, 3.66)

2.42 4.40 6.82

3.35 (2.63, 4.07) 3.35 (2.63, 4.07)

5.52 5.52

-1.00 (-8.75, 6.75) -1.00 (-8.75, 6.75)

1.95 1.95

0.38 (-6.45, 7.21) 0.38 (-6.45, 7.21)

2.28 2.28

0.38 (-2.25, 3.01) 0.38 (-2.25, 3.01)

4.61 4.61

1.54 (-17.23, 20.32) 0.47 8.88 (-12.37, 30.13) 0.37 4.76 (-9.31, 18.83) 0.84 3.50 (-1.28, 8.28) 3.27 0.30 (-15.68, 16.28) 0.62 3.24 (-1.34, 7.82) 3.89 3.19 (1.85, 4.53)

0

100.00

30.1

Fig. 3 – Forest plot results of the effects of garlic on serum level HDL(mg/dl). The black squares represent individual studies and the size of the square represents the weight given to each study in the meta-analysis. The diamond represents the pooled estimate and the horizontal line represents the 95% confidence interval.

after 12 weeks of treatment with garlic, total cholesterol level reduced by 5.7% and LDLc serum level reduced by 11% while there was no significant change in serum HDLc and TG [24]. In studying patients with cardiovascular disease, it was observed that 400 mg of garlic powder consumption for four weeks significantly decreased serum levels of TC, TG, LDL and sig-

nificantly increased HDLc levels and the ratio of HDLc to LDLc [25]. Garlic consumption and its related compounds may increase the excretion of TG from the intestines (due to the presence of polyphenols and dietary fiber in garlic compounds) and suppress degradation of TG (repression of

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

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p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

Study ID

WMD (95% CI)

Iran Emami F (2005) Khademianravandi R (2014) AfkhamiArdakani M (2003) Parastoi K (2004) Zekri R (2012) Mahmoodi M (2011) Mahmoodi M (2005) Mahmoodi M (2011) Bashiri J (2014) Jabbari A (2005) Jabbari A (2005) Aslani N (2013) Subtotal (I-squared = 72.6%, p = 0.000) . Turkey ILKer D (2003) Subtotal (I-squared = .%, p = .) . India Yadav K (2016) Xiao-Hua Z (1997) Subtotal (I-squared = 73.4%, p = 0.052) . USA Gardner Christopher D (2000) Robersuperko H (1999) Subtotal (I-squared = .%, p = .) . Aragh Zuhair M (2013) Subtotal (I-squared = .%, p = .) . Canada Brian W (1998) Adam JA (1995) Subtotal (I-squared = 56.9%, p = 0.128) . Islamabad Rizwan A (2005) Subtotal (I-squared = .%, p = .) . Germany Adeshk J (1992) Subtotal (I-squared = .%, p = .) . England Byrn DJ (1999) Subtotal (I-squared = .%, p = .) . Russia Sobenin I (2007) Subtotal (I-squared = .%, p = .) . Syngapor Xing Lin Ho (2016) Xing Lin Ho (2016) Subtotal (I-squared = 0.0%, p = 0.920) . Korea Eun-Soo Jung M.S (2013) Dae Yun Seo (2012) Subtotal (I-squared = 52.9%, p = 0.145) . Overall (I-squared = 96.2%, p = 0.000) NOTE: Weights are from random effects analysis -82.3

% Weight

-23.40 (-40.95, -5.85) 3.38 0.35 (-15.69, 16.39) 3.59 -15.70 (-32.94, 1.54) 3.42 -28.93 (-45.05, -12.81)3.58 4.88 -2.80 (-9.18, 3.58) 5.21 0.70 (-0.52, 1.92) 5.15 -3.38 (-6.24, -0.52) -2.50 (-3.87, -1.13) 5.21 -7.67 (-25.72, 10.38) 3.31 -0.30 (-19.15, 18.55) 3.20 -0.80 (-17.88, 16.28) 3.44 -14.80 (-28.12, -1.48) 3.97 -4.02 (-6.94, -1.10) 48.35 -57.23 (-82.31, -32.15)2.47 -57.23 (-82.31, -32.15)2.47 -21.51 (-31.80, -11.22)4.40 0.00 (-19.14, 19.14) 3.17 -12.33 (-33.18, 8.52) 7.57 -10.00 (-23.93, 3.93) 3.89 (Excluded) 0.00 -10.00 (-23.93, 3.93) 3.89 -29.33 (-55.17, -3.49) 2.39 -29.33 (-55.17, -3.49) 2.39 10.00 (-31.17, 51.17) 1.30 -23.93 (-38.45, -9.41) 3.80 -12.66 (-43.98, 18.67) 5.11 -30.15 (-32.32, -27.98)5.19 -30.15 (-32.32, -27.98)5.19 -20.00 (-44.86, 4.86) 2.49 -20.00 (-44.86, 4.86) 2.49 -7.72 (-22.81, 7.37) -7.72 (-22.81, 7.37)

3.72 3.72

10.04 (1.79, 18.29) 10.04 (1.79, 18.29)

4.66 4.66

2.70 (-10.35, 15.75) 3.87 (-14.79, 22.53) 3.08 (-7.61, 13.78)

4.01 3.23 7.24

5.11 (-4.55, 14.77) 4.48 -15.00 (-40.25, 10.25) 2.45 -1.42 (-19.88, 17.04) 6.93 -9.65 (-15.07, -4.23) 100.00

0

82.3

Fig. 4 – Forest plot results of the effects of garlic on serum level LDL(mg/dl). The black squares represent individual studies and the size of the square represents the weight given to each study in the meta-analysis. The diamond represents the pooled estimate and the horizontal line represents the 95% confidence interval.

cyclic adenosine monophosphate) and decrease plasma TG by increasing the prostaglandin in adipose tissue. In addition, the results of some research on this point asserted that serum cholesterol-lowering effects of garlic consumption and its products were due to Diallyl disulfide from decomposition of allicin [9,26]. However, the results of some studies have shown that garlic consumption and its products do not have a significant effect on lipid profile changes [27–29]. According to Berthold et al., using garlic oil for 4 weeks had no effect on serum levels of lipid profile and lipopro-

teins [30]. Thomson in 2006 conducted high doses of raw garlic extract to rats with normal blood glucose for 4 weeks (500 mg/kg/day). The high dose of garlic could significantly decrease blood glucose in rats with normal blood glucose levels [31]. In 2005, Demerdash examined hypoglycemia effect of garlic on Alloxan induced diabetic rats. Garlic extract consumption at a dose of 0/4 mg/kg/day for 4 weeks reduced serum levels of glucose in rats [32]. In a double-blind study, Kesewetter in 1991 conducted patients 800 mg/day garlic powder for more than 4 weeks which significantly reduced blood

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p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

Study ID Iran Emami F (2005) Khademianravandi R (2014) AfkhamiArdakani M (2003) Parastoi K (2004) Zekri R (2012) Mahmoodi M (2011) Mahmoodi M (2005) Mahmoodi M (2011) Bashiri J (2014) Jabbari A (2005) Jabbari A (2005) Aslani N (2013) Subtotal (I-squared = 78.2%, p = 0.000) . Turkey ILKer D (2003) Subtotal (I-squared = .%, p = .) . India Yadav K (2016) Bordia A (1997) Xiao-Hua Z (1997) Subtotal (I-squared = 89.5%, p = 0.000) . USA Gardner Christopher D (2000) Robersuperko H (1999) Subtotal (I-squared = 0.0%, p = 0.608) . Aragh Zuhair M (2013) Subtotal (I-squared = .%, p = .) . Canada Brian W (1998) Adam JA (1995) Subtotal (I-squared = 0.0%, p = 0.760) . Islamabad Rizwan A (2005) Subtotal (I-squared = .%, p = .) . Germany Adeshk J (1992) Subtotal (I-squared = .%, p = .) . Russia Sobenin I (2007) Subtotal (I-squared = .%, p = .) . Syngapor Xing Lin Ho (2016) Xing Lin Ho (2016) Subtotal (I-squared = 0.0%, p = 0.443) . Korea Eun-Soo Jung M.S (2013) Dae Yun Seo (2012) Subtotal (I-squared = 0.0%, p = 0.951) . Overall (I-squared = 93.6%, p = 0.000)

WMD (95% CI)

% Weight

-0.84 (-43.63, 41.95) -3.46 (-39.88, 32.96) 4.20 (-38.37, 46.77) 19.42 (-33.87, 72.71) -9.17 (-12.18, -6.16) -9.00 (-13.79, -4.21) 8.20 (-2.50, 18.90) -37.70 (-46.77, -28.63) -10.38 (-67.55, 46.79) -20.90 (-74.22, 32.42) 8.80 (-44.62, 62.22) -33.90 (-93.57, 25.77) -9.82 (-19.07, -0.58)

1.42 1.82 1.44 0.99 6.61 6.43 5.46 5.77 0.88 0.99 0.99 0.82 33.61

-28.62 (-38.86, -18.38) -28.62 (-38.86, -18.38)

5.55 5.55

-23.79 (-42.75, -4.83) -19.80 (-22.36, -17.24) 0.00 (-8.61, 8.61) -13.74 (-28.87, 1.39)

3.89 6.64 5.85 16.38

-7.00 (-44.45, 30.45) 4.30 (-17.24, 25.84) 1.49 (-17.18, 20.16)

1.75 3.46 5.21

-25.09 (-25.77, -24.41) -25.09 (-25.77, -24.41)

6.72 6.72

-11.00 (-39.95, 17.95) -5.01 (-30.36, 20.34) -7.61 (-26.68, 11.46)

2.49 2.92 5.41

1.42 (-2.57, 5.41) 1.42 (-2.57, 5.41)

6.52 6.52

14.00 (-37.78, 65.78) 14.00 (-37.78, 65.78)

1.04 1.04

-40.91 (-50.52, -31.30) -40.91 (-50.52, -31.30)

5.67 5.67

-0.39 (-11.26, 10.48) -8.88 (-27.67, 9.91) -2.52 (-11.93, 6.89)

5.43 3.92 9.34

-19.58 (-50.62, 11.46) -18.20 (-49.20, 12.80) -18.89 (-40.82, 3.04)

2.27 2.28 4.55

-12.44 (-18.19, -6.69)

100.00

NOTE: Weights are from random effects analysis -93.6

0

93.6

Fig. 5 – Forest plot results of the effects of garlic on serum levels TG(mg/dl). The black squares represent individual studies and the size of the square represents the weight given to each study in the meta-analysis. The diamond represents the pooled estimate and the horizontal line represents the 95% confidence interval.

glucose level (11%) [33]. As noted by Anwar in 2003, prescribing garlic oil for 15 days reduced blood glucose in under study rats. Ali in 1995 conducted 40–50 year-old men with 3 grams of fresh garlic daily (approximately one clove of fresh garlic) for 16 weeks. After 26 weeks, no changes in blood glucose level were observed [34]. However, in 1993, Jain et al. did a clinical trial study on the effect of garlic pills on blood glucose. Fourty two healthy subjects were given 300 mg doses

tablets 2 times a day for 12 weeks (drug or placebo). At the end of the study, serum levels of glucose had no significant changes [24]. In 1998, Bordia studied the effect of garlic on blood glucose in patients with heart disease. Thirty patients were given two 1-g capsules twice a day (each capsule contained Atylastat) and compared with control group. Within 1.5–3 months intervention period, there was no change in the level of blood glucose in both groups [35]. Ebadi et al.

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

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%

Study WMD (95% CI)

Weight

Khademianravandi R (2014)

-14.66 (-37.12, 7.80)

3.90

AfkhamiArdakani M (2003)

-7.00 (-20.74, 6.74)

6.57

Parastoi K (2004)

-12.65 (-34.94, 9.64)

3.94

Zamaninoor N (2006)

-4.00 (-8.45, 0.45)

10.38

Mahmoodi M (2011)

-9.77 (-13.36, -6.18)

10.63

Mahmoodi M (2005)

-18.10 (-24.50, -11.70) 9.67

ID Iran

Mahmoodi M (2011)

-6.70 (-7.77, -5.63)

11.08

Subtotal (I-squared = 63.7%, p = 0.011)

-8.90 (-12.32, -5.48)

56.16

. India Yadav K (2016)

-50.50 (-73.55, -27.45) 3.77

Bordia A (1997)

4.00 (2.40, 5.60)

11.03

Xiao-Hua Z (1997)

0.00 (-9.57, 9.57)

8.33

Subtotal (I-squared = 90.9%, p = 0.000)

-10.57 (-28.49, 7.35)

23.12

. Russia Sobenin I (2007)

-54.04 (-66.24, -41.84) 7.19

Subtotal (I-squared = .%, p = .)

-54.04 (-66.24, -41.84) 7.19

. Syngapor Xing Lin Ho (2016)

8.49 (-4.36, 21.34)

6.93

Xing Lin Ho (2016)

-10.04 (-23.71, 3.63)

6.60

Subtotal (I-squared = 73.3%, p = 0.053)

-0.62 (-18.77, 17.54)

13.52

. Overall (I-squared = 94.9%, p = 0.000)

-10.90 (-16.40, -5.40) 100.00

NOTE: Weights are from random effects analysis -73.5

0

73.5

Fig. 6 – Forest plot results of the effects of garlic on serum levels FBS(mg/dl). The black squares represent individual studies and the. size of the square represents the weight given to each study in the meta-analysis. The diamond represents the pooled estimate and the horizontal line represents the 95% confidence interval.

conducted a study in 2007 that involving 60 patients with type 2 diabetes to evaluate the effect of garlic on FBS. The intervention group received 2 garlic tablets 3 times a day at a dose of 400 mg for 3 months. The results showed HgbA1C decrease in the intervention group in comparison to the control group. Also, FBS reduced 49 mg/dl compared with the control group which was 6.4 mg/dl [36] and this effect was consistent with our study. The effect of garlic on lipid profile and blood glucose are shown in studies used in the meta-analysis[17,24,37–68]. In view of the various reports on the effects of garlic on lipid parameters as well as serum glucose, taking this herb can be effective on the aforementioned parameters and the conducted meta-analysis showed it.

side effects of these drugs are their limitation usage in some diabetic patients. Therefore, garlic consumption may be a safe and effective method for patients with mild increases in serum lipid profile and glucose and cannot tolerate chemical drugs.

5.

Acknowledgements

Conclusion

According to the our results in the current study, it can be expressed that garlic reduces lipid profile and blood glucose. Although, there are certain benefits in the use of standard medications for diabetes and increasing serum lipids, the

Conflicts of interest The authors state that they have no conflict of interest.

Hereby, our special thanks are to the research deputy of Ilam University of Medical Sciences, professors who helped us with their guides, and all those who participated in conducting this study.

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

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Study

%

ID

WMD (95% CI)

Weight

Khademianravandi R (2014)

-1.33 (-1.96, -0.70)

16.28

Iran

Parastoi K (2004)

0.00 (-1.18, 1.18)

7.75

Ebadi SA (2005)

-1.50 (-3.74, 0.74)

2.67

Mahmoodi M (2011)

-0.40 (-0.50, -0.30)

28.07

Mahmoodi M (2005)

-0.30 (-13.63, 13.03)

0.08

Mahmoodi M (2011)

0.03 (-0.03, 0.09)

28.40

Subtotal (I-squared = 92.8%, p = 0.000)

-0.42 (-0.80, -0.03)

83.25

Yadav K (2016)

-1.43 (-2.03, -0.83)

16.75

Subtotal (I-squared = .%, p = .)

-1.43 (-2.03, -0.83)

16.75

-0.60 (-0.98, -0.22)

100.00

. India

. Overall (I-squared = 93.2%, p = 0.000)

NOTE: Weights are from random effects analysis -13.6

0

13.6

Fig. 7 – Forest plot results of the effects of garlic on serum levels HbA1C (mg/dl). The black squares represent individual studies and the. size of the square represents the weight given to each study in the meta-analysis. The diamond represents the pooled estimate and the horizontal line represents the 95% confidence interval.

references

[1] R.W. Grant, E.P. McCarthy, D.E. Singer, J.B. Meigs, Frequent outpatient contact and decreasing medication affordability in patients with diabetes from 1997 to 2004, Diabetes Care 29 (6) (2006) 1386–1388. [2] H. King, R.E. Aubert, W.H. Herman, Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections, Diabetes Care 21 (9) (1998) 1414–1431. [3] Y. Chen, G. Reaven, Insulin resistance and atherosclerosis, Diabetes Rev. 5 (4) (1997) 331–342. [4] H. De Wardener, Salt reduction and cardiovascular risk: the anatomy of a myth, J. Hum. Hypertens. 13 (1) (1999) 1. [5] N. Bagdasarian, Andreoli and Carpenter’s Cecil Essentials of Medicine, 5th ed., W. B. Saunders, Philadelphia, 2001, pp. 103–113. [6] A. Chait, Pathogenesis of macrovascular disease in diabetes, Joslin’s Diabetes Mellit. (1994) 648–664. [7] S. Shariathadi, F. Moatar, Herbal Treatment, 13-15, 7th ed., Diba Printer, Argmand: Tehran, 1997, pp. 330–335. [8] A. Cicero, G. Derosa, A. Gaddi, What do herbalists suggest to diabetic patients in order to improve glycemic control? Evaluation of scientific evidence and potential risks, Acta Diabetol. 41 (3) (2004) 91–98. [9] S.K. Banerjee, S.K. Maulik, Effect of garlic on cardiovascular disorders: a review, Nutr. J. 1 (1) (2002) 4.

[10] O. Ohaeri, Effect of garlic oil on the levels of various enzymes in the serum and tissue of streptozotocin diabetic rats, Biosci. Rep. 21 (1) (2001) 19–24. [11] V. Khori, M. Naebpour, A. Mir-Abbasi, A. Salehi, The effects of liquid extract of Allium sativum on the basic and speed-dependent electrophysiological properties of islolated atrioventicular nodal of rabbit, J. Shahrekord Univ. Med. Sci. (2007) 2007. [12] K.C. Agarwal, Therapeutic actions of garlic constituents, Med. Res. Rev. 16 (1) (1996) 111–124. [13] A. Esteghamati, M.M. Gouya, M. Abbasi, A. Delavari, S. Alikhani, F. Alaedini, et al., Prevalence of diabetes and impaired fasting glucose in the adult population of Iran: national survey of risk factors for non-communicable diseases of Iran, Diabetes Care 31 (1) (2008) 96–98. [14] R. Padiya, S.K. Banerjee, Garlic as an anti-diabetic agent: recent progress and patent reviews, Recent Pat. Food Nutr. Agric. 5 (2) (2013) 105–127. [15] S. Banerjee, P.K. Mukherjee, S. Maulik, Garlic as an antioxidant: the good, the bad and the ugly, Phytother. Res. 17 (2) (2003) 97–106. [16] B.G. Hughes, L.D. Lawson, Antimicrobial effects of Allium sativum L. (garlic), Allium ampeloprasum L. (elephant garlic), and Allium cepa L. (onion), garlic compounds and commercial garlic supplement products, Phytother. Res. 5 (4) (1991) 154–158. [17] A. Bordia, S. Verma, K. Srivastava, Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease,

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

PCD-706; No. of Pages 15

ARTICLE IN PRESS

14

p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

[18]

[19]

[20] [21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

Prostaglandins, Leukot. Essent. Fatty Acids 58 (4) (1998) 257–263. P. Mansell, P. Reckless, L. Lloyd, The effect of dried garlic powder tablets on serum lipids in non-insulin dependent diabetic patients, Eur. J. Clin. Res. 8 (1996) 25–26. M. Rahmani, A. Tabari, K. Niaki, S. Allahaverdian, M. Sheikholeslami, Effect of dried garlic supplementation on blood lipids in mild and moderate hypercholesterolemic patients, Arch. Iran. Med. 2 (1999) 19–23. N. Morcos, Modulation of lipid profile by fish oil and garlic combination, J. Natl. Med. Assoc. 89 (10) (1997) 673. X.-H. Zhang, D. Lowe, P. Giles, S. Fell, M.J. Connock, D.J. Maslin, Gender may affect the action of garlic oil on plasma cholesterol and glucose levels of normal subjects, J. Nutr. 131 (5) (2001) 1471–1478. K. Slowing, P. Ganado, M. Sanz, E. Ruiz, T. Tejerina, Study of garlic extracts and fractions on cholesterol plasma levels and vascular reactivity in cholesterol-fed rats, J. Nutr. 131 (3) (2001) 994S–999S. S. Lee, H. Joo, C.-T. Kim, I.-H. Kim, Y. Kim, High hydrostatic pressure extract of garlic increases the HDL cholesterol level via up-regulation of apolipoprotein AI gene expression in rats fed a high-fat diet, Lipids Health Dis. 11 (1) (2012) 77. A.K. Jain, R. Vargas, S. Gotzkowsky, F.G. McMahon, Can garlic reduce levels of serum lipids? A controlled clinical study, Am. J. Med. 94 (6) (1993) 632–635. A.A. Powolny, S.V. Singh, Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds, Cancer Lett. 269 (2) (2008) 305–314. N. Benkeblia, Free-radical scavenging capacity and antioxidant properties of some selected onions (Allium cepa L.) and garlic (Allium sativum L.) extracts, Braz. Arch. Biol. Technol. 48 (5) (2005) 753–759. M.J. Williams, W.H. Sutherland, M.P. McCormick, D.J. Yeoman, S.A. de Jong, Aged garlic extract improves endothelial function in men with coronary artery disease, Phytother. Res. 19 (4) (2005) 314–319. M. Koseoglu, F. Isleten, A. Atay, Y. Kaplan, Effects of acute and subacute garlic supplement administration on serum total antioxidant capacity and lipid parameters in healthy volunteers, Phytother. Res. 24 (3) (2010) 374–378. T. Ratanasuwan, No effect of garlic extract supplement on serum lipid levels in hypercholesterolemic subjects, J. Med. Assoc. Thai. 86 (2003) 750–757. H.K. Berthold, T. Sudhop, K. von Bergmann, Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism: a randomized controlled trial, JAMA 279 (23) (1998) 1900–1902. M. Thomson, K.K. Al-Qattan, T. Bordia, M. Ali, Including garlic in the diet may help lower blood glucose, cholesterol, and triglycerides, J. Nutr. 136 (3) (2006) 800S–802S. F. El-Demerdash, M. Yousef, N.A. El-Naga, Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats, Food Chem. Toxicol. 43 (1) (2005) 57–63. H. Kiesewetter, F. Jung, G. Pindur, E. Jung, C. Mrowietz, E. Wenzel, Effect of garlic on thrombocyte aggregation, microcirculation, and other risk factors, Int. J. Clin. Pharmacol. Therapy Toxicol. 29 (4) (1991) 151–155. M.M. Anwar, A.-R.M. Meki, Oxidative stress in streptozotocin-induced diabetic rats: effects of garlic oil and melatonin, Comp. Biochem. Physiol. A: Mol. Integr. Physiol. 135 (4) (2003) 539–547. A. Bordia, Effect of garlic on blood lipids in patients with coronary heart disease, Am. J. Clin. Nutr. 34 (10) (1981) 2100–2103.

[36] A. Ebadi, E. RahimiLanji, M. Taghdosi, A. Khorshidi, H. Akbari, Effect of garlic tablet on blood glucose in type 2 diabetic patients, Sci. J. Faize 11 (2007) 20–25. [37] F. Emami, B. Naghsh Tabrizi, Evaluation the effect garlet tablet on serum lipid profile, Avicenna J. Clin. Med. 13 (2) (2006) 37–40. [38] R. Khademian-Ravandi, H. Mozaffari-Khosravi, A. Esteghamati, A. Meysami, The effect of garlic tablet on blood glucose, and lipid profile in type 2 diabetic patients&58; a double-blind randomized placebo controlled trial, J. Shahid Sadoughi Univ. Med. Sci. 23 (7) (2015) 621–630. [39] R. Khademian-Ravandi, H. Mozaffari-Khosravi, A. Esteghamati, A. Meysami, The effect of garlic tablet on blood glucose, and lipid profile in type 2 diabetic patients: a double-blind randomized placebo controlled trial, J. Shahid Sadoughi Univ. Med. Sci. 23 (7) (2015) 621–630. [40] K. Parastouei, S. Ravanshad, H. Mostaphavi, E. Setoudehmaram, Effects of garlic tablet on blood sugar, plasma lipids and blood pressure in type 2 diabetic patients with hyperlipidemia, J. Med. Plants 1 (17) (2006) 48–54. [41] R. Zekri, A. Jafari, G. Dehghan, The concurrent effect of one bout aerobic exercise and short-term garlic supplementation on the lipids profile in male non-athletes, J. Shahrekord Univ. Med. Sci. 14 (5) (2012) 34–41. [42] M. Mahmoodi, S.H. Zijoud, G. Hassanshahi, M. Toghroli, M. Khaksari, M. Hajizadeh, et al., The effects of consumption of raw garlic on serum lipid level, blood sugar and a number of effective hormones on lipid and sugar metabolism in hyperglycemic and/or hyperlipidemic individuals—benefit of raw garlic consumption, Adv. Biol. Chem. 1 (02) (2011) 29. [43] M. Mahmoodi, M. Hajizadeh, K. HosseiniSadat, S. Hosseini, G. AsadiKaram, M. Khaksari, et al., Effect of raw garlic on blood biochemical factors in hyperlipidemic and, Bimonthly J. Hormozgan Univ. Med. Sci. 11 (2) (2007) 127–131. [44] M. Mahmoudi, M.R. Hajizadeh, K. Hosseini sadat, S.H.A. Hosseini, G.R. Asadi Karam, M.S.A. Khaksari, Effect of raw garlic on blood biochemical factors in hyperlipidemic and high blood sugar, Hormozgan Univ. Med. Sci. 11 (2) (2007) 127–131. [45] J. Bashiri, The effect of regular aerobic exercise and garlic supplementation on lipid profile and blood pressure in inactive subjects, Zahedan J. Res. Med. Sci. 17 (4) (2015). [46] N. Aslani, M.H. Entezari, G. Askari, Z. Maghsoudi, M.R. Maracy, Effect of garlic and lemon juice mixture on lipid profile and some cardiovascular risk factors in people 30–60 years old with moderate hyperlipidaemia: a randomized clinical trial, Int. J. Prev. Med. 7 (2016). [47] A. Jabbari, H. Argani, A. Ghorbanihaghjo, R. Mahdavi, Comparison between swallowing and chewing of garlic on levels of serum lipids, cyclosporine, creatinine and lipid peroxidation in renal transplant recipients, Lipids Health Dis. 4 (1) (2005) 11. [48] J. Harenberg, C. Giese, R. Zimmermann, Effect of dried garlic on blood coagulation, fibrinolysis, platelet aggregation and serum cholesterol levels in patients with hyperlipoproteinemia, Atherosclerosis 74 (3) (1988) 247–249. [49] I. Durak, M. Kavutcu, B. Aytac¸, A. Avcı, E. Devrim, H. Özbek, et al., Effects of garlic extract consumption on blood lipid and oxidant/antioxidant parameters in humans with high blood cholesterol, J. Nutr. Biochem. 15 (6) (2004) 373–377. [50] F. Irshad, H. Mawani, S. Naz, Allium sativum essential oil (ASEO); effect of supplementation on serum triglycerides, total, cholesterol, HDLC, LDLC and blood cell counts in albino rats, Prof. Med. J. 24 (4) (2017). [51] P. Lachhiramka, S. Patil, Cholesterol lowering property of garlic (Allium sativum) on patients with hypercholesterolemia, Int. J. Med. Sci. Public Health 5 (11) (2016) 2249–2251.

Please cite this article in press as: E. Shabani, et al., The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis, Prim. Care Diab. (2018), https://doi.org/10.1016/j.pcd.2018.07.007

PCD-706; No. of Pages 15

ARTICLE IN PRESS p r i m a r y c a r e d i a b e t e s x x x ( 2 0 1 8 ) xxx–xxx

[52] C.D. Gardner, L.M. Chatterjee, J.J. Carlson, The effect of a garlic preparation on plasma lipid levels in moderately hypercholesterolemic adults, Atherosclerosis 154 (1) (2001) 213–220. [53] I.A. Sobenin, L.V. Nedosugova, L.V. Filatova, M.I. Balabolkin, T.V. Gorchakova, A.N. Orekhov, Metabolic effects of time-released garlic powder tablets in type 2 diabetes mellitus: the results of double-blinded placebo-controlled study, Acta Diabetol. 45 (1) (2008) 1–6. [54] Z.M. Hussien, L.T. Ahmed, Q.G. Hussain, Effect of Atorvastatin And Garlic on Lipid Profile in Hyperlipidemic Patients. [55] A.J. Adler, B.J. Holub, Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men, Am. J. Clin. Nutr. 65 (2) (1997) 445–450. [56] R. Ashraf, K. Aamir, A.R. Shaikh, T. Ahmed, Effects of garlic on dyslipidemia in patients with type 2 diabetes mellitus, J. Ayub Med. Coll. Abbottabad 17 (3) (2005) 60–64. [57] D. Byrne, H. Neil, D. Vallance, A. Winder, A pilot study of garlic consumption shows no significant effect on markers of oxidation or sub-fraction composition of low-density lipoprotein including lipoprotein (a) after allowance for non-compliance and the placebo effect, Clin. Chim. Acta 285 (1–2) (1999) 21–33. [58] E.-S. Jung, S.-H. Park, E.-K. Choi, B.-H. Ryu, B.-H. Park, D.-S. Kim, et al., Reduction of blood lipid parameters by a 12-wk supplementation of aged black garlic: a randomized controlled trial, Nutrition 30 (9) (2014) 1034–1039. [59] D.Y. Seo, S.R. Lee, H.K. Kim, Y.H. Baek, Y.S. Kwak, T.H. Ko, et al., Independent beneficial effects of aged garlic extract intake with regular exercise on cardiovascular risk in postmenopausal women, Nutr. Res. Pract. 6 (3) (2012) 226–231. [60] X.L. Ho, S.Y. Tsen, M.Y. Ng, W.N. Lee, A. Low, W.M. Loke, Aged garlic supplement protects against lipid peroxidation in hypercholesterolemic individuals, J. Med. Food 19 (10) (2016) 931–937.

15

[61] B.W. McCrindle, E. Helden, W.T. Conner, Garlic extract therapy in children with hypercholesterolemia, Arch. Pediatr. Adolesc. Med. 152 (11) (1998) 1089–1094. [62] H.R. Superko, R.M. Krauss, 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. 35 (2) (2000) 321–326. [63] F. Tahbaz, F. Taleban, H. Alavi Majd, T. Neyestani, Effects of garlic ingestion with breakfast on postprandial serum glucose and insulin in type 2 diabetic patients, Iran. J. Nutr. Sci. Food Technol. 1 (3) (2007) 39–44. [64] R. Scicali, A. Di Pino, V. Ferrara, F. Urbano, S. Piro, A.M. Rabuazzo, et al., New treatment options for lipid-lowering therapy in subjects with type 2 diabetes, Acta Diabetol. (2017) 1–10. [65] A. Sahebkar, M.-C. Serban, A. Gluba-Brzózka, D.P. Mikhailidis, A.F. Cicero, J. Rysz, et al., Lipid-modifying effects of nutraceuticals: an evidence-based approach, Nutrition 32 (11) (2016) 1179–1192. [66] A. Sahebkar, C. Serban, S. Ursoniu, M. Banach, Effect of garlic on plasma lipoprotein (a) concentrations: a systematic review and meta-analysis of randomized controlled clinical trials, Nutrition 32 (1) (2016) 33–40. [67] A.F. Cicero, A. Colletti, G. Bajraktari, O. Descamps, D.M. Djuric, M. Ezhov, et al., Lipid-lowering nutraceuticals in clinical practice: position paper from an International lipid expert panel, Nutr. Rev. 75 (9) (2017) 731–767. [68] B. Sosnowska, P. Penson, M. Banach, The role of nutraceuticals in the prevention of cardiovascular disease, Cardiovasc. Diagn. Ther. 7 (Suppl. 1) (2017) S21.

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