Immunomodulatory effect of allium sativum in type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder marked by chronic hyperglycemia and low-grade inflammation, contributing to various complications. Natural agents with immunomodulatory and antioxidant properties have gained attention as adjunct therapies. To review the effects of Allium sativum on inflammatory pathways and metabolic alterations associated with T2DM. A narrative review was performed using PubMed/MEDLINE, EMBASE, and Scielo databases. The search included terms such as “allium sativum”, “inflammation", “oxidative stress”, and “diabetes mellitus”. Studies in English and Spanish - ranging from clinical trials to meta-analyses - were selected based on relevance. Bioactive compounds such as allicin, S-allyl cysteine, and diallyl disulfide exhibit anti-inflammatory, antioxidant, hypoglycemic, and lipid-lowering actions. Preclinical studies show improved glucose metabolism, insulin sensitivity, and organ function. Moreover, clinical evidence supports reductions in fasting glucose, hemoglobin A1c, blood pressure, and oxidative stress, with good safety profiles. Allium sativum appears to be a promising adjuvant in T2DM management, offering metabolic and anti-inflammatory benefits. Nonetheless, further high-quality clinical trials are needed to confirm its long-term efficacy and standardize its therapeutic use.

Key Words: Garlic; Phytotherapy; Anti-inflammatory agents; Antioxidants; Immunomodulating agents; Type 2 diabetes mellitus

Core Tip: Allium sativum (garlic) demonstrates significant potential in managing type 2 diabetes mellitus through its immunomodulatory effects, primarily due to its organosulfur compounds like allicin. Preclinical and clinical studies suggest garlic improves metabolic control by reducing inflammation, oxidative stress, glucose levels, and insulin resistance, with benefits comparable to antidiabetic drugs. It may also positively impact complications such as metabolic-associated fatty liver disease, hypertension, nephropathy, and cardiovascular disease. However, more clinical trials are needed to confirm its therapeutic efficacy and optimize its use in type 2 diabetes mellitus treatment. Garlic offers promise as a natural adjunct to conventional diabetes management.

INTRODUCTION

Diabetes mellitus (DM) is a group of disorders characterized by impaired carbohydrate metabolism, wherein the body’s ability to utilize glucose as an energy source is diminished, while endogenous glucose production increases, resulting in chronic hyperglycemia[1]. In 2021, it was reported that 10.5% of the adult population was affected by DM[2]. DM contributes to a significant burden of complications, including hypertension, coronary artery disease, osteoarthritis, depression, asthma, various types of cancer, and infections, all of which reduce life expectancy in affected individuals[3]. Among the pathophysiological mechanisms underlying type 2 DM (T2DM), oxidative stress, endoplasmic reticulum stress, amyloid deposition in the pancreas, ectopic lipid accumulation in muscle, liver, and pancreas, as well as lipotoxicity and glucotoxicity, play key roles. These factors may induce an inflammatory response or be exacerbated by inflammation[4].

Various forms of metabolic stress that promote insulin resistance and T2DM also activate stress- and inflammation-induced kinases, such as IkappaB kinase and c-Jun N-terminal kinase. IkappaB kinase, in turn, activates the nuclear factor kappa B (NF-κB) transcription factor, leading to the expression of pro-inflammatory genes, such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and IL-1β, in the liver and adipose tissue. On the other hand, c-Jun N-terminal kinase activates transcription factors such as the Ets-like protein 1 and activating transcription factor 2[4,5]. In individuals with obesity, hypoxia in expanding adipose tissue can trigger an inflammatory response through increased secretion of chemokines such as C-C motif ligand 2, which recruits monocytes, and adipokines such as leptin and adiponectin, which have potential immunomodulatory effects[4,5].

Preclinical evidence supports the use of natural products with significant effects on various signaling pathways, including mitogen-activated protein kinases, the phosphatidylinositol 3-kinase/protein kinase B system, NF-κB, and the Janus kinase/signal transducer and activator of transcription pathway. These compounds also play a crucial role in regulating the balance between T helper 17 cells and regulatory T cells, as well as in modulating oxidative stress. Through these mechanisms, they have been shown to regulate the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-8, and IL-17, and anti-inflammatory cytokines such as IL-2 and IL-10. This knowledge forms the basis for the traditional use of medicinal plants in the treatment of immune-related diseases[6-9]. Recent research highlights allium sativum bioactive compounds, like allicin and S-allyl cysteine, which reduce oxidative stress and inflammation in T2DM, offering promising therapeutic potential[10-14]. The aim of this article is to review the immunomodulatory effects of allium sativum in the inflammatory process of patients with T2DM.

LITERATURE REVIEW

A narrative review was conducted through a bibliographic search in the PubMed/MEDLINE, EMBASE, and Scielo databases, focusing on the search terms “allium sativum”, “garlic”, “inflammation”, “anti-inflammatory”, “oxidative stress”, “antioxidative”, “diabetes mellitus”, “GLYCEM”, “dyslipidemia”, “lipid lowering”, “liver”, “MASLD”, “kidney”, “nephropathy”, and “cardiovascular disease”. Systematic reviews, meta-analyses, clinical trials, preclinical studies, narrative reviews, retrospective studies, cross-sectional studies, prospective studies, and case reports were included, all closely aligned with the objectives of this manuscript. The search was limited to documents written in Spanish or English, excluding conference abstracts. Articles were not excluded based on their publication date. A total of 122 articles were included and are cited in the references section.

ALLIUM SATIVUM EXHIBITS POTENT IMMUNOMODULATORY PROPERTIES IN THE CONTEXT OF T2DM

Preclinical and clinical studies consistently demonstrate its efficacy in improving glycemic control, modulating oxidative stress, and attenuating systemic inflammation. Moreover, garlic supplementation has shown favorable effects on comorbid conditions, including dyslipidemia, hypertension, and metabolic dysfunction-associated steatotic liver disease (MASLD), with a significant reduction in inflammatory markers such as C-reactive protein (CRP) and TNF-α. Its bioactive compounds - particularly allicin, diallyl disulfide (DADS), and S-allyl cysteine - play a pivotal role in regulating pro- and anti-inflammatory cytokine profiles, enhancing antioxidant defenses, and ameliorating diabetes-associated complications such as nephropathy and retinopathy[11-14]. These findings support the therapeutic potential of Allium sativum as an adjunctive strategy in the holistic management of T2DM.

CHEMICAL COMPOSITION OF ALLIUM SATIVUM

Allium sativum (garlic) is the second largest species in the Allium genus, after onion, and belongs to the subfamily Allioideae within the family Amaryllidaceae (formerly known as the Liliaceae family)[10,11]. Garlic has a long history of medicinal use as an antimicrobial, immunomodulator, antioxidant, anticancer, and anti-aging agent[11]. The primary active compounds in garlic (Figure 1) are organosulfur compounds, such as allicin, alliin, ajoene (in both E and Z forms), S-allylcysteine, diallyl sulfide (DAS), DADS, diallyl trisulfide (DATS), and vinyl dithiins, as well as saponins, phenolic compounds (e.g., β-resorcylic acid, pyrogallol, gallic acid, rutin, protocatechuic acid, quercetin), polysaccharides, and other components such as fatty acids, amino acids, vitamins, and minerals[12-16]. Allicin, the most biologically active sulfur compound in garlic, is lipophilic and responsible for its characteristic odor and taste[17]. It represents between 70% and 80% of garlic’s bioactive components[18]. Allicin is formed from alliin through the action of the enzyme alliinase, which is activated when garlic is cut or crushed[17-19]. Subsequently, allicin rapidly decomposes into other components due to heat exposure[19].

Figure 1 Active components and medicinal properties of garlic. DADS: Diallyl disulfide; DAS: Diallyl sulfide; DATS: Diallyl trisulfide.

PROPERTIES OF GARLIC COMPONENTS

Regarding its antimicrobial effects, the antibacterial activity of garlic is mainly attributed to allicin[17,20], while its fungicidal effect is attributed to allicin, DADS, and DATS[17]. Both antiparasitic and antiviral activities are linked to allicin, ajoene, and DATS[16,17,21]. The antitumoral activity of garlic is believed to result from the enhancement of p38 expression by allicin, alliin, DADS, and DAS, inhibition of tumor vascularization, and promotion of apoptosis in cancer cells. Additionally, ajoene stimulates apoptosis, promotes peroxide production, and increases the activity of caspases-3 and caspases-8[17,18,22-24].

Allicin, DADS, and DATS are the primary antioxidant compounds in garlic, acting through the modulation of reactive oxygen species (ROS), increasing glutathione levels, and activating cellular antioxidant enzymes. Alliin, in turn, regulates ROS generation and prevents the activation of mitogen-activated protein kinases. Furthermore, DADS suppresses the enzymatic activity of cytochrome P450 2E1, reducing the production of reactive oxygen and nitrogen species[17,22,25,26]. Garlic has also been shown to protect against various natural, chemical, and industrial toxicities, as well as the adverse effects of medications, suggesting its potential as an antidote[27]. Allicin exhibits anti-inflammatory activity by inhibiting stromal cell-derived factor 1 alpha and the transendothelial migration of neutrophils. Meanwhile, DADS reduces the expression of inflammatory cytokines such as NF-κB, IL-1β, and TNF-α, as well as ROS generation, by suppressing the activity of cytochrome P450 2E1. Additionally, thiacremonone blocks NF-κB activity[17,22,28,29].

Concerning obesity, ajoene stimulates adipocyte apoptosis, reduces fat accumulation, and decreases body weight gain by activating adenosine monophosphate-activated protein kinase and increasing thermogenesis[17,30]. 1,2-vinyl dithiol decreases the expression of CCAAT/enhancer-binding protein alpha, peroxisome proliferator-activated receptor gamma 2, and lipoprotein lipase[17,31]. DAS, allicin, cysteine sulfoxide, S-allylcysteine sulfoxide, and alliin exhibit antidiabetic properties by enhancing insulin production[17,32]. Furthermore, hypolipidemic effects have been observed with various garlic preparations[17]. Allicin and DADS also reduce both systolic and diastolic blood pressure, while gamma-glutamylcysteine inhibits angiotensin-converting enzyme (ACE)[17,22,23,33].

EVIDENCE ON THE EFFECT OF GARLIC ON INFLAMMATION AND OXIDATION

The chemical compounds in garlic can reduce inflammatory markers through the regulation of IL-10 and NF-κB[34]. Studies have found that garlic reduces levels of CRP and TNF-α, although results regarding its effect on IL-6 Levels have been inconsistent[34-41]. Garlic does not appear to have a significant effect on leptin (pro-inflammatory) or adiponectin (anti-inflammatory) levels[35]. Furthermore, garlic enhances the proliferation and activation of immune cells, such as γδ-T cells and natural killer cells[42], while reducing the number of natural killer T cells, indicating a modulatory effect on the immune system and inflammation[39].

Garlic can improve oxidative stress through various mechanisms, including the reduction of superoxide radical production, enhancement of enzymatic and non-enzymatic antioxidant activity and expression, and the reduction of certain pro-oxidant enzymes[44]. Garlic supplementation has been shown to increase serum levels of total antioxidant capacity, reduced glutathione, and superoxide dismutase, while decreasing serum levels of malondialdehyde[43-47]. Raw garlic exhibits higher antioxidant capacity than cooked garlic. Additionally, the ethanolic extract of garlic sprouts demonstrated superior antioxidant activity compared to raw garlic extract, while aged black garlic displayed more prominent antioxidant properties than fresh garlic[48-50] This is likely due to the fact that although aged black garlic contains less allicin, it has a higher concentration of polyphenols and flavonoids[51].

EVIDENCE ON THE EFFECT OF GARLIC IN DIABETES

Preclinical studies

In vitro, silver nanoparticles ranging from 10 nm to 30 nm, synthesized from garlic, increased glucose utilization, reduced hepatic glucose production, inhibited starch-digesting enzymes such as α-amylase and α-glucosidase, and stimulated pancreatic insulin secretion[52]. In studies conducted in rats with streptozotocin- or alloxan-induced DM, various garlic preparations were administered, including raw garlic extract (125 mg/kg/day, 250 mg/kg/day, 500 mg/kg/day, or 750 mg/kg/day, orally or intraperitoneally), ethanolic garlic extract (0.1 g/kg/day, 0.25 g/kg/day, or 0.5 g/kg/day, orally), aged garlic, garlic extract combined with “Vernonia amygdalina”, and aqueous extracts of garlic, ginger, and cayenne pepper (200 mg/kg/day or 500 mg/kg/day), over periods ranging from 1 weeks to 8 weeks. The results showed a reduction in glucose levels[43,44,53-59], glycosylated hemoglobin A1c (HbA1c)[44,55,56] and histopathological alterations[55,58], as well as an increase in serum insulin levels[44,54,57,59,60], improvement in insulin resistance[57] and body weight[43,59,60]. In some studies, the effects were dose-dependent[44,59], and were comparable to or even greater than those observed with glibenclamide or metformin[44,54,55,59]. In rabbits, similar reductions in glucose levels were also observed[61].

Clinical studies

In patients with T2DM, garlic supplementation (300-1500 mg/day) has been associated with reductions in fasting glucose (-17 to 29 mg/dL), HbA1c (-0.4% to 0.8%) and improved insulin sensitivity. Similarly, in our trial, a polyherbal compound containing 300 mg of garlic, along with aloe vera, fenugreek, milk thistle, black seed and psyllium, reduced HbA1c by 0.5% and significantly lowered triglycerides (-40 mg/dL), total cholesterol (-35 mg/dL), and LDL (-28 mg/dL) after 12 weeks, outperforming the control group under standard therapy alone[62,63]. The results showed a reduction in fasting glucose[62,64-68], postprandial glucose[67,68], HbA1c[63,66,68] and insulin resistance[68]. In some studies, these effects were dose-dependent[66] and duration-dependent[66], with results comparable to or even superior to those observed with metformin[66,67]. No adverse effects on renal or hepatic function were reported[63,68]. On the other hand, studies that administered raw garlic (300 mg/day or 3 cloves per day for 2 weeks) or aged garlic (1200 mg/day for 4 weeks) did not show significant effects on the reduction of fasting glucose[63,69,70]. Systematic reviews and meta-analyses have demonstrated that garlic, in various forms (powder: 300 mg/day to 22400 mg/day, oil: 4000 mg/day, aged garlic extract: 1200-6000 mg/day, raw garlic: 4000 mg/day, and enteric-coated supplements: 800 mg/day), administered over periods ranging from 3 weeks to 1 year, can significantly reduce blood glucose levels, HbA1c, and fructosamine[71,72], as well as improve insulin resistance[72], without increasing the frequency of complications[73].

GARLIC AND DIABETES-ASSOCIATED COMORBIDITIES

Dyslipidemia

In rat studies with streptozotocin- or alloxan-induced DM, various garlic preparations were used: Raw garlic extract (250-500 mg/kg/day, intraperitoneally), ethanolic extract (0.1-0.5 g/kg/day, orally), aged garlic, and aqueous garlic with ginger and cayenne pepper (200-500 mg/kg/day). Treatments lasted from 1 week to 24 weeks. These showed dose-dependent reductions in total cholesterol (TC) and triglycerides (TG)[44,53,54,56,59]. Similar TC reductions were seen in rabbits[61]. In T2DM patients, raw garlic (300 mg/day), garlic tablets (300 mg three times/day), or tablets with 1.3% allicin (300 mg twice/day) were given alone or with standard treatment for 4-24 weeks. Results included reduced TC, low-density lipoprotein cholesterol (LDL), and TG[63,65,74], and increased high-density lipoprotein cholesterol (HDL)[65,74], without adverse kidney or liver effects[63].

However, aged garlic (1200 mg/day for 4 weeks) showed no significant change in TC or TG[70,74]. Systematic reviews and meta-analyses report that garlic (powder: 300-22400 mg/day, oil: 4000 mg/day, aged extract: 1200-6000 mg/day, raw: 4000 mg/day, enteric-coated: 800 mg/day) for 3 weeks to 1 year may lower TC[72,73,75-77], LDL[72,73,77], and TG[75,76], and raise HDL[72]. Still, some studies found no significant changes in LDL, HDL[75,76], apolipoprotein B[75], or TG[72]. Effects often depended on treatment duration and initial lipid levels[75]. No increase in complications was reported[73]. Yet, due to low-certainty evidence, more high-quality studies are needed. Some reviews found no significant impact of garlic on lipid profiles[78,79].

MASLD

In studies conducted on rats with streptozotocin- or alloxan-induced DM, various garlic preparations were administered, including ethanolic garlic extract (0.1 g/kg/day, 0.25 g/kg/day, or 0.5 g/kg/day, orally), aged garlic, aqueous garlic extract (100 mg/kg/day or 200 mg/kg/day), and an aqueous extract of garlic, ginger, and cayenne pepper (200 mg/kg/day or 500 mg/kg/day) over periods ranging from 1 week to 8 weeks. The results showed a reduction, normalization, or prevention of elevated levels of liver enzymes such as aspartate aminotransferase, alanine aminotransferase[44,54,59,80] and lactate dehydrogenase[44], as well as a reduction in liver lipid peroxidation[56] and repair of DM-induced liver damage[59], in a dose-dependent manner[44,56].

In mice fed a high-fat diet, essential garlic oil (50 mg/kg and 100 mg/kg) and DADS (20 mg/kg) significantly reduced the release of proinflammatory cytokines in the liver and increased antioxidant capacity by inhibiting the expression of cytochrome P450 2E1, thereby protecting against the development of MASLD[81]. In adults with mild liver dysfunction, the administration of fermented garlic extracts over a 12-week period resulted in improved levels of gamma-glutamyl transferase (P = 0.066) and alanine aminotransferase (P = 0.014), with no additional adverse effects[82].

A systematic review and meta-analysis in animal models of MASLD revealed that garlic improves metabolic parameters associated with the development of the disease, such as blood glucose, insulin, and lipid levels[83]. Another systematic review, which included both animal and human studies, suggested that garlic could regulate the progression of MASLD through mechanisms such as weight reduction, modulation of lipid and glucose metabolism, and reduction of inflammation and oxidative stress[84]. A meta-analysis in humans demonstrated that the likelihood of reducing hepatic steatosis with garlic was 2.75 times higher than with placebo (P < 0.001), with improvements in liver enzymes and metabolic parameters[85]. Furthermore, another meta-analysis in humans indicated that garlic significantly reduces liver enzymes and decreases the likelihood of being diagnosed with MASLD by 46%[86].

Hypertension

Hypertension, which is common in patients with T2DM, is a key risk factor for cardiovascular disease (CVD) and microvascular complications[87]. Garlic, due to its content of allicin and DADS, exerts antihypertensive effects in a dose-dependent manner by inhibiting ACE, reducing the synthesis of vasoconstrictor prostanoids, increasing nitric oxide levels, and reversing arterial remodeling[33,88]. It has been shown to effectively reduce both systolic and diastolic blood pressure without increasing serious adverse effects[38,70,88-98].

In preclinical studies, garlic components have been found to inhibit ACE and reduce the concentration of angiotensin II, acting synergistically with drugs that block the renin-angiotensin system. Additionally, garlic improves the oral bioavailability of nifedipine and propranolol. When combined with carvedilol or atenolol, garlic prevents myocardial damage and reduces oxidative stress[99,100]. Based on the section discussed, Table 1 provides a brief overview of the proposed mechanisms and effects of garlic on cardiometabolic disorders.

Table 1 Main clinical effects of garlic in cardiometabolic disorders: Dyslipidemia, metabolic dysfunction-associated steatotic liver disease, and hypertension.

Condition	Mechanisms and Effects
Dyslipidemia	↓ TC, TG, LDL
	↑ HDL
	Garlic forms: Raw, tablets, aged
	Effect varies with dose and duration
MASLD	↓ Liver enzymes (ALT, AST, GGT)
	↓ Lipid peroxidation
	↑ Antioxidant activity
	Improves metabolic parameters
Hypertension	ACE inhibition
	↓ Systolic/diastolic blood pressure
	↑ NO levels
	Arterial remodeling
	Synergistic with drugs

TC: Total cholesterol; TG: Triglycerides; LDL: Low-density lipoprotein cholesterol; HDL: High-density lipoprotein cholesterol; MASLD: Metabolic dysfunction-associated steatotic liver disease; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transpeptidase; ACE: Angiotensin-converting enzyme; NO: Nitric oxide.

GARLIC AND DIABETES COMPLICATIONS

Nephropathy

Studies conducted in streptozotocin- or alloxan-induced diabetic rat models have employed various garlic preparations - raw garlic extract (500 mg/kg, intraperitoneally), ethanolic garlic extract (0.1-0.5 g/kg/day, orally), aged garlic, allicin (16 mg/kg/day), aqueous garlic extract (100-2000 mg/kg/day), and mixed aqueous extracts of garlic, ginger, and cayenne pepper (200-500 mg/kg/day) - administered over 1 week to 8 weeks. These interventions consistently demonstrated reductions, normalization, or prevention of elevated serum urea and creatinine levels[54,59,80]. Garlic exhibits nephroprotective effects in diabetic models primarily through its antioxidant and anti-inflammatory properties. Aqueous garlic extract (2 g/kg/day) significantly lowered serum urea, creatinine, and uric acid concentrations, decreased renal malondialdehyde and total oxidant status, while enhancing total antioxidant capacity and reducing renal TNF-α and nitric oxide levels[101].

Similarly, allicin administration (16 mg/kg/day) improved renal function by reducing proteinuria, creatinine clearance, and urinary N-acetyl-β-D-glucosaminidase, while attenuating oxidative stress and suppressing proinflammatory cytokines, including IL-1β, IL-6, NF-κB, and transforming growth factor β1[102]. Furthermore, garlic supplementation reduced urinary protein loss[53], particularly albuminuria[103], and decreased serum uric acid levels[54]. Histopathological analyses revealed partial renal tissue repair[59,101], with efficacy in some studies exceeding that of glibenclamide[59]. Additional nephroprotective effects included reduced excretion of N-acetyl-β-D-glucosaminidase[102,103], diminished renal lipid peroxidation[56,103], and lowered expression of inflammatory mediators (IL-1β, IL-6, TNF-α, NF-κB)[101,102]. Notably, garlic reversed the diabetes-induced upregulation of angiotensin II type 1 receptors and the downregulation of type 2 receptors[103]. Many of these effects were shown to be dose-dependent[56,59]. A recent systematic review and meta-analysis reinforced garlic’s therapeutic potential in diabetic kidney disease, identifying optimal nephroprotective outcomes at garlic doses of 500 mg/kg for 8-10 weeks or garlic component doses of 45-150 mg/kg over 4-10 weeks[104].

Retinopathy

Garlic enhances the function of brain-derived neurotrophic factor, conferring neuroprotective properties and positioning it as a complementary option in the treatment of patients with diabetic retinopathy in combination with conventional therapies. In addition, garlic suppresses the action of vascular endothelial growth factor, contributing to the reduction of angiogenesis, and inhibits the activity of hypoxia-inducible factor 1, both key factors in the development of this pathology[105]. In a study conducted in rats with streptozotocin-induced DM, raw garlic extract (0.4 g/100 g body weight) administered for 7 weeks showed favorable effects in improving morphological changes in the retina[106].

Cardiovascular disease

Individuals with DM are at increased risk of CVD, which is not solely attributable to the alterations caused by hyperglycemia but also to excess ectopic fat[107]. Several studies have found that garlic consumption is significantly associated with increased levels of HDL cholesterol and apolipoprotein A, as well as a reduction in TC, TG, LDL, CRP, IL-6, homocysteine, and coronary artery calcium, suggesting that garlic may reduce risk factors for CVD[38,70,71,108-116]. However, other studies have not observed any benefits in terms of reducing CVD risk[90,117-119].

Adverse effects and toxicity

Although garlic does not contain known toxic compounds and administration of garlic to rats at doses of 50 mg/kg shows no clinical adverse effects, doses exceeding 200 mg/kg may cause liver damage and impair antioxidant mechanisms[18,120,121]. Excessive consumption of raw garlic on an empty stomach may disrupt the gut microbiota. Topical application can cause painful lesions, rashes, and burns. In rodents, daily administration of 50 mg of garlic powder over extended periods inhibits spermatogenesis. Long-term exposure to high doses results in anemia and weight loss due to red blood cell lysis[18,121]. Additionally, studies have shown that allicin, one of the main active compounds of garlic, although beneficial in certain diabetic complications such as diabetic retinopathy through its antioxidative and anti-inflammatory properties mediated by activation of phosphatase and tensin homolog induced putative kinase 1/parkin-mitophagy and inhibition of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome, also possesses bioactivity that could potentially affect systemic physiological processes[121]. Garlic may interact with anticoagulant and antiplatelet drugs, increasing the risk of bleeding. This effect raises concerns for surgical patients, as it can prolong bleeding time. Caution is advised when combining garlic with medications such as warfarin, aspirin, or clopidogrel[122].

LIMITATIONS OF THE EVIDENCE AND AREAS FOR FUTURE RESEARCH

Further research is needed to expand knowledge on the bioactive components of garlic, as well as its biological functions and mechanisms of action. Studies have demonstrated promising roles of compounds like allicin, particularly in oxidative stress regulation and inflammation control, as observed in experimental models of diabetic complications such as diabetic retinopathy[121]. It is also critical to study the potential impact of processing techniques on its efficacy and safety, as these may alter the concentration and activity of key compounds[120]. Moreover clinical trials in humans are required to validate the health benefits of garlic observed in preclinical studies, with a particular focus on assessing its safety and potential adverse effects. However, current evidence is still limited by factors such as short intervention periods, small sample sizes, and lack of standardized garlic preparations, which may affect the reproducibility and generalizability of the findings[120,122].

CONCLUSION

Garlic emerges as a potentially beneficial adjunct in the management of T2DM and its comorbidities or complications, demonstrating significant effects in reducing serum lipids, improving liver and kidney parameters, and regulating blood pressure and oxidative stress. Its antihypertensive, hypolipidemic, hepatoprotective, antioxidant, and anti-inflammatory properties have been evidenced in preclinical studies some clinical trials and even meta-analysis, although results vary depending on the dose, form of administration, and duration of treatment. Nevertheless, the limited quality and heterogeneity of the available evidence underscores the need for more rigorous clinical studies to confirm these findings, optimize therapeutic applications, and assess its long-term safety.