GARLIC

There are few cancer clinical trials with garlic, though one study in advanced digestive system disease showed protective effects on NK (natural killer) T-cells of the immune system (Highlight 2). Where garlic has broad clinical evidence is in endothelial (blood vessel) health in other systemic inflammatory conditions, where it suppresses several common bio-markers strongly indicated in cancer growth and spread.

Aged black garlic is able to reduce endothelial adhesion molecules (MCP-1, ICAM-1, VCAM-1) crucial not only in heart disease but strongly implicated in metastasis. Even in healthy individuals, aged black garlic supplements measurably reduced the rates of blood platelet aggregation (see References) The fermentation process produces the actie compound S-allyl-cysteine indicated in lab studies to increase effects of garlic.

In studies with patients having some type of systemic inflammatory condition, garlic supplements show a moderate reduction in the c-reactive protein and IL-6 markers of inflammation, and an increase in IL-12 all of which indicate positive effects needed in metabolic health including cancer. Aged black garlic at 2.4g daily for 12 months showed strong reductions in key inflammatory markers IL-6 and c-reactive protein in otherwise healthy women ( Highlight 4). Similarly, aged black garlic has been shown to improve levels of adiponectin, a hormone important to healthy metabolism including glucose and insulin sensitivity. Low levels are associated to progression in several cancers including breast, prostate and kidney cancer.

Similarly, a clinical trial on chronic inflammation in obesity showed 400mg of garlic extract could also reduce Plasminogen Activator Inhibitor-1, a marker of blood coagulation or clotting levels. Upregulated levels of this protein are strongly linked to the spread of ovarian, colorectal, lung, bladder and most types of breast cancer.

Studies show sufficient levels of B12 can be linked to responses to garlic. In prevention, research shows mixed findings though some tendencies to protective effects in digestive cancers particularly colorectal. Clinical trials have used very diverse forms and doses of garlic, maybe the clearest protocol is from 2.4mg daily of aged black garlic extract sustained over time- look for high quality extracts such as Kyolic AGE or similar and can be a useful complement to garlic as a functional food.

Use both raw and cooked garlic. To help chopped garlic retain its active compounds during cooking, let it rest for ten minutes before heating.

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Highlighted Studies

Moreover, in our study black garlic consumption decreased the levels of MCP-1 in both populations studied. MCP-1 is a chemokine released by the endothelium that regulates monocytes and leukocytes migration and infiltration. It has been associated with the development of atheroma plaques and different pathologies with inflammatory components. Its decrease in black garlic consumption could contribute to reducing the inflammatory response and its progression.

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The NK cell activity was not different between the 2 groups before or 3 mo after the administering treatment. The NK cell activity increased significantly in the AGE group. It also increased in the control group, but the increase was not significant. The NK cell activity appeared to decrease rapidly in the control group compared with the AGE group. Five subjects (22%) in the control group showed >25% decrease in the NK cell activity but none did in the AGE group

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Dietary supplementation with AGE significantly inhibited both the total percentage and initial rate of platelet aggregation at concentrations of ADP up to 10 ��mol/L. The KM for ADP-induced aggregation were approximately doubled after supplementation with AGE, whereas the maximum rate of aggregation was unaffected….. We conclude that AGE, when taken as a dietary supplement by normolipidemic subjects, may be beneficial in protecting against cardiovascular disease as a result of inhib...

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AGE ameliorates atherosclerosis and type 2 diabetes through the suppression of inflammation. AGE modulates the inflammatory response by enhancing the phosphorylation of AMP-activated protein kinase (AMPK) [23]. AMPK plays an important role in regulating the inflammatory response through the inhibition of the TLR signaling pathway. Therefore, AGE may prove to be useful for the prevention and improvement of various diseases associated with chronic inflammation

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TABLE OF REFERENCES

URLRatingHighlightHighlight 2Visuals (click)
https://www.sciencedirect.com/science/article/pii/S00223166221659462.5Meta-analysisIn the current meta-analysis, garlic supplementation significantly reduced serum concentrations of inflammatory biomarkers including CRP, IL-6, and TNF. There were clinically significant reductions of 0.61 mg/L and 0.73 ng/L in serum concentrations of CRP and IL-6, respectively, but a reduction of only 0.26 ng/L for TNF. However, the effects of garlic on serum concentrations of adiponectin and leptin were not significant. The current meta-analysis showed a significant reduction (0.61 mg/L) in serum CRP concentrations after garlic supplementation, compared to among controls. CRP is an acute phase protein that plays a critical role in the human innate immune response. We found a significant reduction in IL-6 concentrations after garlic supplementation compared with controls. IL-6 is a proinflammatory cytokine mostly secreted by T-cells and macrophages to stimulate the immune response during infection and tissue damage (13, 14). A narrative review on this topic showed that intake of garlic compounds might inhibit NF-κB, a transcription factor that regulates gene transcription of several cytokines involved in proinflammatory responses, including TNF, IL-1β, IL-6, monocyte chemotactic protein-1, and IL-12 (61).
https://onlinelibrary.wiley.com/doi/full/10.1155/2021/66368752.5Human studyThe present study concluded that 12 months of AGE treatment had a lowering effect on the inflammatory biomarker IL-6. AGE has in prior clinical and preclinical studies shown a beneficial effect on inflammation [22, 23], with a significant lowering effect on IL-6; however, this is the first time it has been shown to have a lowering effect in a female cohort with a low risk of cardiovascular disease. AGE has immunomodulatory effects, among other things, through its application of antioxidants. S-1-propenylcysteine (S1PC) and SAC are the two predominant sulfur-containing amino acids present in AGEIL-6 was measured at 0 and 12 months of either AGE or placebo treatment. At baseline, at 0 months of treatment of either AGE or placebo, the IL-6 concentration was 4.762 ± 0.701 ng/L in the AGE group and 4.173 ± 0.653 ng/L in the placebo group (p > 0.05). After 12 months of treatment, the IL-6 concentration was 3.754 ± 0.493 ng/L in the AGE group and 4.573 ± 0.461 ng/L in the placebo group (p > 0.05). The differences between the two groups were calculated as mean annular percent change
https://jn.nutrition.org/article/S0022-3166(22)14296-3/fulltext2.5Human studyIn contrast, ADP-induced platelet aggregation was inhibited by the AGE supplementation regimen used in our study (Fig. 1, Table 1). We postulate that the most likely mechanism for this involves the ADP receptor. Platelet ADP receptors belong to the P2T subtype of purinoreceptors whose activation leads to a rise in intracellular Ca2+. Thus, one possibility would be that AGE inhibits the ADP-induced rise in cytosolic Ca2+ concentrations. Indeed, aqueous extracts of crushed garlic have been shown to inhibit the uptake of Ca2+ into plateletsDietary supplementation with AGE significantly inhibited both the total percentage and initial rate of platelet aggregation at concentrations of ADP up to 10 μmol/L. The KM for ADP-induced aggregation were approximately doubled after supplementation with AGE, whereas the maximum rate of aggregation was unaffected. No significant changes in plasma thromboxane B2 and 6-ketoprostaglandin F1α concentrations or serum lipid profiles were observed. We conclude that AGE, when taken as a dietary supplement by normolipidemic subjects, may be beneficial in protecting against cardiovascular disease as a result of inhibiting platelet aggregation.
https://www.sciencedirect.com/science/article/pii/S0022316622081524?via%3Dihub2.5Human study - adjunctAGE ameliorates atherosclerosis and type 2 diabetes through the suppression of inflammation. AGE modulates the inflammatory response by enhancing the phosphorylation of AMP-activated protein kinase (AMPK) [23]. AMPK plays an important role in regulating the inflammatory response through the inhibition of the TLR signaling pathway. Therefore, AGE may prove to be useful for the prevention and improvement of various diseases associated with chronic inflammationThe NK cell activity was not different between the 2 groups before or 3 mo after the administering treatment. The NK cell activity increased significantly in the AGE group. It also increased in the control group, but the increase was not significant. The NK cell activity appeared to decrease rapidly in the control group compared with the AGE group. Five subjects (22%) in the control group showed >25% decrease in the NK cell activity but none did in the AGE group (P = 0.051) (Table 3, Fig. 1). Only 1 (3%) of the 35 patients in whom the NK cell activity did not decrease by 25% or more 3 mo after administering treatment died within the following 3 mo, but 3 (60%) of the 5 patients in whom the NK cell activity decreased by 25% or more died within the following 3 mo
https://www.sciencedirect.com/science/article/abs/pii/S07533322173649582.5Human studyThis randomized, double-blind, placebo-controlled trial demonstrates that supplementation with GE favorably modifies endothelial biomarkers associated with cardiovascular risk and suggests that GE can be used to suppress chronic inflammation..At the end of study SI (p = 0.01), hsCRP (p < 0.001, PAI-1 (p < 0.001), LDL cholesterol (p < 0.001), and TAS (p < 0.01) were reduced in the GE-supplemented group, but not in the placebo group.Ninety-two subjects were enrolled in this study. The participants were randomly assigned to receive 400 mg of GE or placebo daily for 3 months. The arterial stiffness index (SI) and markers of endothelial function such as high-sensitivity C-reactive protein (hsCRP), cholesterol (total, LDL, HDL), triglycerides, and plasminogen activator inhibitor 1 (PAI-1)...supplementation with GE favorably modifies endothelial biomarkers associated with cardiovascular risk and suggests that GE can be used to suppress chronic inflammation in obese individuals.
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-019-1204-62Human studyAs the main finding, this study showed that garlic can be effective in reducing the inflammatory biomarkers in ESRD patients. We observed that the levels of IL-6, CRP and ESR significantly decreased after the end of 8-week period in garlic-treated group. Similar to our study, Mozaffari-Khosravi et al. [18] investigated the effect of garlic on pro-inflammatory markers in 44 postmenopausal osteoporotic women and did not observe a significant difference in inflammatory cytokines of IL-1, IL-6 and tumor necrosis factor alpha (TNF-α) between garlic and placebo groups. They saw a significant reduction in TNF-α just in garlic group after the intervention Baseline versus after-intervention median (IQR) of IL-6 (pg/ml), CRP (mg/L) and mean ± SD of ESR (mm) in garlic and placebo groups was 2.2 (0.8, 6.4) versus 0.7 (0.6, 1.2) (p <  0.001) and 2.0 (0.8, 2.1) versus 0.6 (0.6, 0.8) (p = 0.002), 13.0 (5.0, 14.0) versus 2.0 (1.0, 9.0) (p <  0.001) and 7.0 (2.0, 10.0) versus 6.0 (3.7, 7.5) (p = 0.547) and 35.4 ± 21.7 versus 50.7 ± 28.5 (p = 0.021) and 46.0 ± 26.0 versus 45.3 ± 22.3 (p = 0.797). Median (IQR) of Percentage Before-After change in CRP was − 71.4%(− 85.7, − 42.9%) and − 20.0%(− 30.0, 114.3%) in garlic and placebo group respectively.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10385333/2Human studyThe intervention consisted of the ingestion of 4 cloves of black garlic (12 g) daily for 12 weeks. Results: significant increases in Apolipoprotein (Apo)A1 occurred in both groups: Hypercholesterolemia (Δ 11.8 mg/dL) vs Healthy (Δ 11.1 mg/dL). Besides, significant reductions for endothelial adhesion molecules monocyte chemoattractant protein-1 (MCP-1) (Δ −121.5 pg/mLvs. Δ −56.3 pg/mL), intracellular adhesion molecule-1 (ICAM-1) (Δ −39.3 ng/mL vs. Δ 63.5 ng/mL), and vascular cyto-adhesion molecule-1 (VCAM-1) (Δ −144.4 ng/mL vs. Δ −83.4 ng/mL ) were observed, for hypercholesterolemic and healthy subjects, respectively.In vitro studies have shown that garlic components suppress VCAM-1 and ICAM-1 expression in HCAEC endothelial cell cultures, decreasing monocyte adherence [39], by affecting signaling pathways [40]. Similarly, garlic extracts effectively suppressed the expression of VCAM-1, the activation of NF-κβ transcription factor, and monocyte adhesion [41]. No data have been reported up to date on changes in selectins with black garlic treatment. Moreover, in our study black garlic consumption decreased the levels of MCP-1 in both populations studied. MCP-1 is a chemokine released by the endothelium that regulates monocytes and leukocytes migration and infiltration. It has been associated with the development of atheroma plaques and different pathologies with inflammatory components. Its decrease in black garlic consumption could contribute to reducing the inflammatory response and its progression.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3603419/2Human studyDouble-blind, crossover, randomized, placebo-controlled clinical trial to assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12 weeks of AGE and 12 weeks of placebo), on subjects with MS. Results. The administration of AGE increased the plasma levels of adiponectin (P = 0.027). No serious side effects associated with the intervention were reported. Conclusion. The present results have shown for the first time that the administration of AGE for 12 weeks increased plasma adiponectin levels in patients with MS. This suggests that AGE might be a useful, novel, nonpharmacological therapeutic intervention to increase adiponectinAdiponectin exerts an anti-inflammatory effect through activation of its three receptors (AdipoR1, AdipoR2, and T-cadherin) [9]. The activation of AdipoR1 and R2 results in increased hepatic and skeletal muscle fatty acid oxidation, increased skeletal muscle lactate production, reduced hepatic gluconeogenesis, increased cellular glucose uptake, and inhibition of inflammation and oxidative stress [30]. Activation of T-cadherin is protective in vascular endothelial cells against oxidative stress-induced apoptosis [31]. Several mechanisms have been suggested to explain the anti-inflammatory effects of adiponectin, including direct actions on inflammatory cells, actions on NF-κB, and interaction with TNF-α [9]. It has been demonstrated that adiponectin inhibits the expression of adhesion molecules in endothelia
https://www.mdpi.com/2072-6643/16/11/17552Human studySkin microvascular peak flow during post-occlusive reactive hyperemia significantly increased in the purple garlic oil group compared to the placebo group (between-group difference [95%CI]: 15.4 [1.5 to 29.4] PU; p = 0.031). Likewise, hs-CRP levels decreased in the purple garlic group compared to the control group (−1.3 [−2.5 to −0.0] mg/L; p = 0.049). Furthermore, we observed a significant reduction in the mean number of MetS components in the purple garlic group after five weeks (1.7 ± 0.9 vs. 1.3 ± 1.1, p = 0.021). In summary, regular consumption of encapsulated purple garlic oil significantly improved microvascular function, subclinical inflammatory status, and the overall MetS profile in a population with cardiometabolic alterationsIn our study, urinary F2-isoprostanes/creatinine levels, a surrogate biomarker of oxidative stress, did not change after five weeks of intervention. These results, combined with those of VCAM-1 and PAI-1, could suggest that a longer period of administration may be necessary to have an effect on circulating biomarkers of oxidative stress and endothelial dysfunction in untreated subjects with mild cardiometabolic alterations. Nevertheless, our functional and biochemical findings jointly provide evidence for a protective role of purple garlic oil on endothelium
https://clinicalnutritionespen.com/article/S2405-4577(17)30259-0/fulltext2Human studyIn this 6-week, double-blind, randomized, placebo-controlled clinical study, we determined the effects of AGE supplementation on immune cells and markers of inflammation. In adults with obesity, we found that 6 weeks of AGE supplementation was able to modulate immune cell distribution and prevent the increase of serum concentrations of IL-6 and TNF-α, factors that play important roles in the development of obesity-induced inflammation. Moreover, blood LDL levels, which often increase with obesity...were significantly lower after AGE supplementationRegular consumption of encapsulated purple garlic oil significantly improved microvascular function in a population with cardiometabolic alterations. Additional benefits were also observed in subclinical inflammatory status and the components of MetS. Thus, purple garlic oil may play a potential role in the management of cardiometabolic disorders at early stages, when pharmacological treatment is not yet indicated. Nevertheless, further research is needed to establish the long-term benefits of purple garlic oil in microvasculature in different patient populations.
https://www.mdpi.com/2072-6643/16/11/16922Meta-analysisThe aim of this systematic evaluation was to investigate the effect of garlic on glycolipid metabolism in adults, and 22 RCTs were included; we found that garlic significantly modulated FBG, HbA1c, TC, LDL, and HDL in patients but had no effect on TG levels. Due to the high heterogeneity of findings, a random effects model was used in all of the following stages. The duration of the intervention period for the studies included in the meta-analysis was 3 weeks−1 year, and the types of garlic included raw garlic, aged garlic extract, and garlic powder tablets. The results showed that garlic has a beneficial effect on blood glucose and blood lipid in humans, and their association was statistically significant.Our study showed that garlic consumption had a significant effect on TC, LDL and HDL. Garlic’s ability to modulate TC, LDL, HDL and TG has been linked to various conditions stemming from disrupted lipid metabolism. These include nonalcoholic fatty liver disease, coronary artery disease, and the development of atherosclerosis [55,56]. This might have been possible due to the presence of the allicin compound and its derivatives by inhibiting the HMG–CoA reductase enzyme [35,57,58]. In addition, the active ingredient SAC in garlic attenuated free-fatty-acid-induced adipogenesis in human HepG2 cells by activating an AMP-activated protein kinase dependent pathway [16]. Studies have shown that aged garlic extract can improve insulin resistance, which may be related to its effect on the gut microbiota

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