Exploring the health benefits of raw white garlic consumption in humans: a mini review

Introduction Raw white garlic, a fundamental food in both culinary and medicinal practices globally, has gained attention for its potential health benefits. Despite widespread use, clinical research has predominantly focused on aged black garlic or garlic extracts, leaving raw white garlic consumption in humans underexplored. This mini review aims to summarize the evidence from clinical and observational studies on the health effects of raw white garlic consumption. Methods A search in PubMed and Scopus databases was conducted to identify clinical and observational studies on raw white garlic consumption. Twelve clinical trials and 10 observational studies meeting the predefined inclusion criteria were selected for review. Results Results from clinical trials revealed diverse health effects of raw garlic consumption, including improved lipid profiles, blood pressure regulation, fibrinolytic activity, antioxidant status, and glucose metabolism. Observational studies reported the association of raw garlic consumption with improvements of important health outcomes, including cancer risk, cardiovascular disease, insulin homeostasis, and liver function. However, both clinical and observational studies were heterogenous in design, participant characteristics, durations, and outcome measures. Observational studies were limited to Asian populations. Conclusion While human studies indicate that raw garlic may exert various health benefits, larger randomized controlled trials with longer follow-up and cohort studies are needed to explore the full potential of raw garlic consumption in human health promotion. Our mini-review aims to summarize the currently available evidence on raw garlic consumption in humans.


Introduction
Meta-analyses show lipid-lowering nutraceuticals like garlic, red yeast rice, plant sterols and further similar compounds are effective and safe, with no major safety issues have been found (1).They may improve lipid levels in those with mild-to-moderate dyslipidemia and low cardiovascular risk (1).Raw white garlic has been a culinary and medicinal pillar across cultures (2), and its potential health benefits have intrigued researchers.However, most clinical studies exploring the health effects of garlic on humans have predominantly focused on aged black garlic or garlic extracts (3,4)-often as proprietary formulations and sold as expensive dietary supplements.While these studies provide valuable insights into the potential health effects of garlic compounds, their extrapolation to raw white garlic is limited due to the altered chemical composition resulting from the aging process or extraction methods (5).Various drying methods employed in industry to prepare different garlic products result in decreased levels of bioactive constituents such as allicin, total phenols, and pyruvate compared to freshly harvested garlic (5).Instead, they contain various products resulting from allicin transformation.For example, sulfur compounds in fresh garlic may be nearly 1,000 times more potent antioxidants compared to those in aged garlic extract (6).The inconsistencies between research focused on garlic supplements versus traditional raw white garlic consumption worldwide highlights the need for comprehensive investigations into the health benefits and mechanisms of action of raw garlic.Future research could provide a holistic understanding of the potential benefits associated with the consumption of raw garlic.Therefore, the aim of this mini review is to explore current evidence on the potential benefits of raw garlic consumption from clinical and observational studies conducted in humans.

Methods
PubMed and Scopus electronic databases were used for literature search using the following search terms: ("raw garlic" OR "white garlic") without limiting the publication dates.Only studies with human participants published in English were extracted.Only trials that used raw white garlic as the intervention, or observational studies examining the associations of consumption of raw white garlic with health benefits were included.Studies involving other garlic preparations such as dried garlic, garlic oil or juice extracted from raw crushed garlic were excluded.The initial search hits were cleared from duplicates and subsequent screened, leading to the selection of 12 clinical trials (7-18) and 10 observational (19-28) studies.
The heterogeneity regarding dosage, participants, duration of intervention and outcomes highlight the need for further welldesigned clinical trials investigating potential health effects of raw garlic.In addition, drawing conclusive insights is challenging, especially considering the limited number of studies addressing various disease conditions.

Discussion
In the present mini review, we identified 12 clinical trials and 10 observational studies on the health effects of raw white garlic consumption.The clinical trials indicated improvements in (cardio) metabolic biomarkers, fibrinolytic activity, and anthropometric measures.The identified observational studies suggested that raw garlic intake had beneficial effects on prehypertension, handgrip strength, risk of different types of cancer, thickened cIMT, insulin homeostasis, and newly diagnosed NAFLD.
The potential benefits for human health observed in intervention and observational studies can be explained by a range of mechanisms.Garlic bulbs contain around 2.3% organic sulfur compounds, with alliin comprising 80% of cysteine sulfoxide (29).When garlic is crushed, these compounds react with alliinase to form allicin, making up 70-80% of resulting thiosulfinates, which are unstable in nature and quickly decompose into various sulfur compounds like diallyl sulfide diallyl disulfide, diallyl tetrasulfide, diallyl trisulfide, ajoene and further compounds (5,29).
The cardiovascular protection primarily revolve around reducing lipid levels, attenuating oxidative stress, antiplatelet effects, inhibiting angiogenesis, safeguarding the endothelial cell layer, reducing inflammation, and these processes are mediated through various signaling pathways (such as AMPK/TLRs, GEF-H1/RhoA/Rac, PPARγ/ LXRα, Keap1/Nrf2 and PI3K/AKT) as described by Li and colleagues (30).The main antilipemic effect is attributed to the inhibition of cholesterol synthesis by inhibiting the activity of hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA), a key enzyme in cholesterol synthesis (30) and by blocking CD36 expression and oxidized LDL (oxLDL) uptake in human macrophages through the PPARγ pathway, potentially preventing atherosclerotic lesions (31,32).Garlic compounds may exert their antioxidative effects mainly through enhancing levels and/or activity of SOD, CAT and GPx (6,32), scavenging free radicals and attenuating lipid peroxidation (6).Garlic can have antithrombotic effects by inhibiting cyclooxygenase-mediated thromboxane synthesis (6) and by interacting with the biosynthesis of prostaglandins via cyclooxygenase 1 inhibition and with fibrinogen receptors (15).To summarize, antiplatelet activity of garlic compounds may come from various pathways, including the reduced synthesis of prothrombotic factors like cyclooxygenase-1, thromboxanes, leukotrienes, prostaglandins, and a reduced secretion of arachidonic acid from phospholipids and coagulation factor IV from platelets (30).Additionally, garlic's ability to inhibit platelet aggregation induced by calcium ion aggregates may further contribute to its antiplatelet effects (30).Proposed anticancer effects of garlic compounds may be based on a wider range of mechanisms, such as altering mitochondrial permeability, inhibiting angiogenesis and invasion, scavenging free radicals and preventing the formation of DNA adducts, activating enzymes for carcinogen detoxification, regulating cell proliferation and apoptosis, maintaining chromosome stability and immune response, modifying histones, inhibiting carcinogenic activation, and altering protein degradation dependence on the proteasome (6,29).
Garlic and its extracts have no known toxic compounds (6).In rats, administration in high doses of garlic powder (500 mg/kg) resulted in changes in lung and liver tissue, indicating dose-related toxicity, but low doses (50 mg/kg) had little effect (33).Long-term supplementation of high doses of fresh garlic homogenate (1,000 mg/ kg per day) in rats caused significant reductions in endogenous antioxidants (catalase and SOD) without altering lipid peroxidation levels and the animals treated with this dose showed morphological changes in the liver, indicating liver injury (34).This study also found that garlic in low doses had the potential to enhance the antioxidant status, but at higher doses a reversal of these effects was observed (6,34).In humans, garlic is generally considered safe by regulatory authorities, but can cause gastric irritation and different side effects, including gastrointestinal discomfort and body odor, especially at high doses (6).Thus, the acceptability of higher doses of raw garlic needs to be considered in future intervention studies.
While recognizing the constraints of the present study, the findings should be approached with caution due to the necessity for further standardized methods in future research on this topic to assure the reliability of the trials included.Some studies exhibited small sample sizes and often had short durations, which is why generalizability remains uncertain.Also, the epidemiological investigations predominantly originated from China, underlining the necessity for additional epidemiological data from different locations to spot potential geographical variations, if any.In the meantime, it is essential to acknowledge the health-promoting findings from these studies and the valuable data they provide, indicating promising trends in improving human health.If future research supports these results, raw garlic may become a potential contributor to dietary guidelines aimed at enhancing human health.

Future perspectives
In conclusion, the lack of clinical studies specifically dedicated to raw white garlic represents a significant gap in the understanding of its health benefits -despite its affordability and widespread availability -and hinders the development of evidence-based dietary recommendations on garlic consumption.The reliance on research involving aged black garlic and garlic extracts limits the generalizability of findings to the widely consumed raw white garlic.The gap in research is evident given the distinct chemical composition of raw garlic compared to its aged counterparts or extracts and existing studies often lack unity in garlic preparation, dosage, and duration, making it challenging to draw meaningful conclusions about the unique properties of garlic (5,35).To fully appreciate and utilize the potential health benefits of this easily accessible vegetable, research should prioritize and conduct well planned clinical trials focused on raw garlic, exploring its unique properties and applications in promoting human health.

Publisher's note
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TABLE 1
Clinical studies investigating the effects of raw garlic on human health.

TABLE 2
Observational studies investigating the effects of raw garlic on human health.