From the distinctive smell to therapeutic effects: Garlic for cardiovascular, hepatic, gut, diabetes and chronic kidney disease

doi:10.1016/j.clnu.2021.03.005

Clinical Nutrition

Volume 40, Issue 7, July 2021, Pages 4807-4819

https://doi.org/10.1016/j.clnu.2021.03.005 Get rights and content

Summary

Garlic, a member of the Allium family, widely used in cooking for many centuries, displays well described antioxidant and anti-inflammatory properties, as a result of its constituent organosulfur compounds, such as alliin, allicin, ajoene S-allyl-cysteine, diallyl sulfide and diallyl disulfide, among others. Although garlic has demonstrated beneficial effects in cardiovascular disease, diabetes, and cancer, its efficacy as a therapeutic intervention in chronic kidney disease remains to be proven. This review thus focuses on the potential benefits of garlic as a treatment option in chronic kidney disease. and its ability to mitigate associated cardiovascular complications and gut dysbiosis.

Introduction

Garlic (Allium sativum L.) is a well-known herb that has been used for many years as a culinary flavoring agent. Besides its flavor attributes, the biological functions of garlic have been widely studied and the salutogenic properties of its constituent sulfur containing compounds demonstrated. These have been respectively ascribed as anti-inflammatory, antidiabetic, antioncogenic, antimicrobial, antioxidant, cardioprotective, immunomodulatory and hepatoprotective in nature [[1], [2], [3], [4], [5]].

Due to its potent anti-inflammatory and antioxidant properties garlic is a good nutritional food candidate for use in a “Food as Medicine” approach for chronic kidney disease (CKD) [6,7]. In fact, the uremic milieu is characterized by a prematurely aged phenotype linked with chronic inflammation and oxidative stress that should be possible to target with garlic [8,9]. CKD patients also present with an altered composition of their gut microbiota, associated with increased uremic toxin production, which exacerbates oxidative stress levels and inflammatory burden [10]. However, there are only a limited number of studies in patients with CKD that have investigated the effect of garlic on inflammatory markers, lipid profile, gut microbiota, and other essential biomarkers.

A nutritional intervention strategy based on food, however, is not without merit. The literature shows that various bioactive nutritional compounds, such as resveratrol, curcumin, selenium, can be part of an important nutritional strategy to mitigate inflammation, oxidative stress and dysbiosis [[11], [12], [13], [14], [15]]. This narrative review will elucidate the salutogenic properties of garlic as a nutritional intervention in CKD and shed some light on how garlic could mitigate the pathogenic complications associated with co-morbid conditions in patients with CKD.

Section snippets

Garlic

Garlic belongs to the Liliaceae family, known for its historical nutritional as well its medicinal use. It has several physiological functions, such as lowering blood glucose and lipid levels, improving the function of the immune system, contributing to the capacity of mineral absorption, preventing constipation, acting in the reduction of body fat levels, restricting proliferation of microorganisms and regulating intestinal tract peristalsis [[16], [17], [18]].

Fresh garlic contains water

Metabolism and bioavailability

The recommended dosage for the therapeutic use of garlic should have sufficient allicin bioavailability potential, which represents 2–4 g of crushed raw garlic as a daily dose [27]; or 7.2 g of age garlic extract or one dried garlic powder tablet twice to thrice per day [28]. According to the U.S. Food and Drug Administration (FDA), garlic is considered safe for humans. However, some side effects can be induced with ingestion of high doses by a sensitive individual, such as gastric agitation,

Garlic as antioxidant and anti-inflammatory food

Compounds from garlic such as alliin, allyl cysteine, diallyl disulfide, and allyl disulfide are scavengers of superoxide anion radicals that can mitigate the lipid peroxidation [21]. Moreover, garlic can activate the nuclear factor-erythroid 2-related factor 2 (Nrf2), which is responsible for activation of the antioxidant response elements (ARE) and production of phase II antioxidant and detoxifying enzymes, such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione

Hepatoprotective effect of garlic

Administration of garlic as an intervention can be of benefit in the treatment of liver diseases, due to its salutogenic properties [49]. Studies in animal models have already demonstrated the potential benefits of garlic in the treatment of alcoholic liver disease (ALD) [50]. Indeed, the hepatoprotective capacity can be attributed to the oil-soluble organosulfur compounds (CSOs) present in garlic, which seem to increase the activity of hepatic antioxidant enzymes (e.g., glutathione, catalase,

Cardiovascular protective effects of garlic

The effects of garlic on cardiovascular diseases have been extensively investigated since the 1960s. Raw garlic became an object of investigation as it became apparent that most people who regularly consumed large amounts of garlic had low cholesterol levels [60]. Thus, Orekhov et al. [61] were able to demonstrate that garlic could have anti-atherogenic properties by acting directly on the arterial wall, reducing and preventing lipid accumulation. A comprehensive meta-analysis has shown that

Beneficial effects of garlic on the microbiota

Several factors can influence the composition of the gut microbiota, including ageing, nutrition, medication, lifestyle, immune function and underlying disease [13,97]. An imbalance in the composition of the intestinal microbiota is termed dysbiosis. This condition correlates directly with the pathogenesis and progression of chronic non-communicable diseases [98,99]. In this context, food has been studied as a critical element in gut microbiota modulation. Specifically, garlic may be an

Garlic and diabetes mellitus

Garlic has been used as an antidiabetic nutritional component, as it can improve insulin sensitivity; decrease hyperglycemia, promote inhibition of intestinal glucosidase and reduce cholesterol, triacylglycerol and LDL-cholesterol plasma levels [106,107]. Moreover, the improvement in the glycemic homeostasis promoted by garlic may be due to increased glucose transporter (GLUT)-4 translocation, glucose uptake and insulin action [108,109] and also by improving antioxidant responses by increasing

Could garlic be of benefit in chronic kidney disease?

Many chronic complications are associated with the uremic phenotype such as inflammation, dysbiosis and oxidative stress that contributes to CVD, progression of renal failure, immunological disorders, low nutritional status, osteoporosis, premature ageing and mortality [8,9,144,145]. Although still limited, the number of studies in patients with CKD using dietary components and their potent bioactive compounds, aiming to decrease inflammation and oxidative stress, are continually rising [[11],

Conclusion

As garlic has potent anti-inflammatory and antioxidant effects it offers a promising and simple but effective means of mitigating complications often observed in diseases of ageing, such as CKD and its co-morbidities. Additionally, garlic may be beneficial to the maintenance of a normative gut microbiota and thus enhanced age-related physiological resilience. Finally, as patients with CKD have many complications linked to chronic inflammation, oxidative stress, and uremic dysbiosis, garlic

Financial support

Conselho Nacional de Pesquisa (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) support Denise Mafra research.

Conflict of interest

There are no conflicts of interest to declare.

Acknowledgments

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) support Denise Mafra research. The Heart and Lung Foundation, Karolinska Institutet Diabetic Theme Centre, INTRICARE, CaReSyAn and “Njurfonden” support Peter Stenvinkel's research. Paul G Shiels is funded by studentship awards from 4D Pharma and Constant Pharma Ltd.

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Allicin ameliorates glucose and lipid metabolism via modulation of gut microbiota and bile acid profile in diabetic rats
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Diabetes mellitus is a widely prevalent chronic disease, and effective treatments for it remain limited. Allicin has anti-diabetic effect, however, the detailed mechanism has not been well investigated. The diabetic rats were treated with allicin for 6 weeks, and then the fecal samples, serum and tissues were collected for measurement of gut microbiota (GM), bile acids (BAs) and other indexes. Allicin decreased the blood glucose levels, serum lipid levels, and alleviated hepatic lipid deposition of the diabetic rats. Simultaneously, allicin changed the composition of GM and increased secondary BAs in serum. Interestingly, allicin significantly increased the glucagon-like peptide-1 (GLP-1) content in colon homogenate, and reduced the protein expression of fibroblast growth factor 15 (FGF15) in ileum. Moreover, allicin increased 7α-hydroxylase 1 (CYP7A1) expression in liver. The study demonstrated that allicin ameliorates metabolisms in the diabetic rats though modulating gut microbiota, bile acids, and inhibiting enterohepatic FGF15-CYP7A1 signaling.
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Organosulfur compounds, phenolic compounds, and ascorbic acids (AsA) are known to account for the bulk of chive’s (Allium schoenoprasum L.) antioxidant properties. This study uncovered the contribution of each of these compounds to the chive's antioxidant activity under different storage conditions. The results showed that room temperature (RT) accelerated the accumulation of reactive oxygen species, though phenolics, organosulfur compounds, activities of antioxidant enzymes, and scavenging activity toward hydroxyl radical (OH) and superoxide anion (O₂⁻) were observed to be enhanced in chives stored at RT. In contrast, AsA content, DPPH (1,1-diphenyl-1-picrylhydrazyl) scavenging and FRAP (ferric reducing antioxidant power) activity of the chive were increased by LT on day 5. Furthermore, S-alk(en)ylcysteine sulfoxides (CSOs) showed OH scavenging and weak DPPH scavenging but had no O₂⁻ scavenging and FRAP capacity. Volatile organosulfur compounds showed no antioxidant activities. Conclusively, the data demonstrated that AsA was largely responsible for DPPH scavenging and FRAP activity of the chive, while phenolic compounds, especially vanillic acid and p-hydroxybenzoic acid, were primarily responsible for OH and O₂⁻ scavenging activity.
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Narrative ReviewFrom the distinctive smell to therapeutic effects: Garlic for cardiovascular, hepatic, gut, diabetes and chronic kidney disease

Summary

Introduction

Section snippets

Garlic

Metabolism and bioavailability

Garlic as antioxidant and anti-inflammatory food

Hepatoprotective effect of garlic

Cardiovascular protective effects of garlic

Beneficial effects of garlic on the microbiota

Garlic and diabetes mellitus

Could garlic be of benefit in chronic kidney disease?

Conclusion

Financial support

Conflict of interest

Acknowledgments

J Ren Nutr

J Ren Nutr

J Ethnopharmacol

Fibre

Food Chem

Int J Biol Macromol

J Food Drug Anal

Eur J Med Chem

Nutr Res

Eur J Pharmacol

Life Sci

J Pharmacol Sci

Int Immunopharm

Hepatobiliary Pancreat Dis Int

Food Chem Toxicol

Sci Total Environ

J Nutr

Effects of Garlic on Atherosclerosis Nutrition

Phytomedicine

Chin J Nat Med

J Nutr

Phytomedicine

Food Chem Toxicol

Biomed Pharmacother

Clin Nutr ESPEN

Cell

Allicin: chemistry and biological properties

Molecules

Antioxidant action and therapeutic efficacy of Allium sativum

L. Molecules

Evaluation of garlic cultivars for polyphenolic content and antioxidant properties

PloS One

Compounds from Allium species with cytotoxic and antimicrobial activity

Phytochemistry Rev

Hepatoprotective and antioxidant effects of single clove garlic against CCl4-induced hepatic damage in rabbits

BMC Compl Alternative Med

Allium vegetable intakes and the incidence of cardiovascular disease, hypertension, chronic kidney disease, and type 2 diabetes in adults: a longitudinal follow-up study

J Hypertens

Evaluating the effect of garlic extract on serum inflammatory markers of peritoneal dialysis patients: a randomized double-blind clinical trial study

BMC Nephrol

Inflammation and premature ageing in chronic kidney disease

Toxins

Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy

Lancet

Brazil nut consumption modulates Nrf2 expression in hemodialysis patients: a pilot study

Mol Nutr Food Res

Dietary components that may influence the disturbed gut microbiota in chronic kidney disease

Nutrients

Impact of curcumin supplementation on expression of inflammatory transcription factors in hemodialysis patients: a pilot randomized, double-blind, controlled

Clin Nutr

Food as medicine: targeting the uraemic phenotype in chronic kidney disease

Nat Rev Nephrol

Garlic for cardiovascular disease: prevention or treatment?

Curr Pharmaceut Des

Garlic and resveratrol attenuate diabetic complications, loss of β-cells, pancreatic and hepatic oxidative stress in streptozotocin-induced diabetic rats

Front Pharmacol

Chemistry of aged garlic: diversity of constituents in aged garlic extract and their production mechanisms via the combination of chemical and enzymatic reactions

Exp Ther Med

Biological and chemical stability of garlic-derived allicin

J Agric Food Chem

Bioactive compounds and biological functions of garlic (allium sativum L.)

Foods

Allicin bioavailability and bioequivalence from garlic supplements and garlic foods

Nutrients

Narrative Review
From the distinctive smell to therapeutic effects: Garlic for cardiovascular, hepatic, gut, diabetes and chronic kidney disease