COFFEE

Coffee beans contain highly active compounds including cholorogenic and caffeic acid, polyphenols kahweol and cafestol. Caffeine is also indicated for positive actions in some studies. Clinical trials in multiple cancer types have shown improved patient outcomes from coffee consumption. Particularly advanced colorectal (CRC) cancer patients in multiple studies show longer relative survival rates in the 40% range. In the CRC case, caffeinated coffee usually, but not always, shows the greatest impact – decaffinated coffee has also shown strong outcomes in at least one CRC study (see Examples). Particularly those consuming at least 4 cups of coffee per day.

Swedish researchers found a relative risk reduction in recurrence of about a half in ER+ variant breast cancer patients during treatment with tamoxifen (see Highlight 2). The pre-clinical results focus on caffeine mainly, and its effects in breast cancer cell lines of reducing estrogen and insulin like growth factor receptor activity.

In prostate cancer, recent studies shine a light on the crucial importance of genotypes that steer caffeine metabolism. About half of patients with the CYP1A2  enzyme with AA geneotype with faster coffee metabolism saw large 70% or so reductions in progression risk but only at moderate 1-3 cups – each put at 230mg caffeine. (See Examples). And yes, there are DNA testing companies that can help identify caffeine metabolizer status. The other half, probably should consider decaffinated and use of green coffee extracts in moderation.

A small but fascinating GBM (brain cancer) trial in 2023 showed injected chorogenic acid having some striking impacts. The overall survival of these patients even for CGA alone was significantly extended to over 11 months, roughly double the timespan of typical oncology treatment (See references). Dose levels from 2 to 7 mg/ kg daily are perhaps 5 to 10x dietary intake. CGA is entering final approval stages for GBM in the chinese FDA process. Whilst these levels are higher than supplements can deliver, green coffee extracts are interesting too (see Supplements)

Population studies show reduced cancer incidence for multiple cancer types related to higher coffee consumption (see Examples)

Active compounds are high in unprocessed green coffee. Then lightly roasted beans, french press brewing and filtered coffee – especially with re-usable metallic filters.  In regards to decaffinated beans, some studies during oncology treatment show higher effects. Though rare forms of kidney cancer have been linked to decaf coffee in otherwise healthy populations. The proteins in standard milk reduce availability of the active compounds in coffee by about a half. Cream so non dairy is a better option, including almond, oat or soy milks ideally with lower protein and higher fat composition.

EXAMPLES OF IMPROVED OUTCOMES

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PRE-DIAGNOSIS OR PREVENTION

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Highlighted Studies

In 1171 patients with advanced or metastatic CRC [colorectal cancer], we found that increased total coffee intake was associated with a statistically significant improvement in both OS [overall survival] and PFS [progression free]. When caffeinated coffee and decaffeinated coffee were considered separately, both were associated with improved OS, whereas the association with PFS was attenuated [lower] for caffeinated coffee. The significant association between higher coffee intake and improved...

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…we demonstrate an association between increasing coffee consumption and significantly smaller invasive tumor sizes, whereas concomitantly lower proportion of ER+ tumors among women with breast cancer. ..in vitro data show that caffeine and caffeic acid attenuated the growth of predominantly ER+, but also ER−, human breast cancer cells by modulating ER and IGFIR levels… Finally, the present study demonstrate that tamoxifen-treated women ...

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In the multivariable model adjusting for PSA, age and tumor length, compared to 0 cups/day, <1 cup (HR 0.85) [hazard ratio], 1–1.9 cups (HR 0.64) 2–3.9 cups (HR 0.71) and ≥4 cups (HR 1.67) were not significantly associated with progression-free survival… Patients with low/moderate coffee intake and the AA “fast caffeine metabolizer” genotype were less likely to experience grade progression, as compared to non-consumers (HR 0.36)..Low to moderate coffee intake appears safe i...

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The recurrence of HCC contributes in a considerable manner to mortality after OLT. Even with improved patient selection and implementation of the Milan‐criteria, recurrence occurs in around 20%..results show that consumption of caffeinated coffee is associated with a decreased risk of HCC recurrence and beneficial survival following OLT [transplant] Experimental data suggest that such clinical benefits of coffee is associated, at least in part, with the antagonistactivity of caffeine on ade...

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TABLE OF REFERENCES

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https://jamanetwork.com/journals/jamaoncology/fullarticle/27702625Human study - adjunctIn 1171 patients with advanced or metastatic CRC, we found that increased total coffee intake was associated with a statistically significant improvement in both OS and PFS. When caffeinated coffee and decaffeinated coffee were considered separately, both were associated with improved OS, whereas the association with PFS was attenuated for caffeinated coffee. The significant association between higher coffee intake and improved patient outcomes remained even after multivariate adjustment for potential confounding and prognostic variables.Coffee is the largest source of dietary antioxidants in the United States.35 Studies have implicated high oxidative stress in CRC development and metastases.36,37 As such, a greater consumption of antioxidants could potentially slow the development of such cancers. In addition, kahweol is another component in coffee with anti-inflammatory and proapoptotic effects that may decrease mutagenesis and cancer progression.8,9,38 Further research is ongoing to identify other bioactive molecules in coffee and their effect on cancer in humans. Both insulin sensitization and other anticancer effects may work in combination to slow tumor growth and development.
https://aacrjournals.org/clincancerres/article/21/8/1877/79074/Caffeine-and-Caffeic-Acid-Inhibit-Growth-and5Meta-analysiswe demonstrate an association between increasing coffee consumption and significantly smaller invasive tumor sizes, whereas concomitantly lower proportion of ER+ tumors among women with breast cancer. Moreover, in the present study, mechanistic in vitro data show that caffeine and caffeic acid attenuated the growth of predominantly ER+, but also ER−, human breast cancer cells by modulating ER and IGFIR levels with impact on downstream effectors and cell-cycle progression. Finally, the present study demonstrate that tamoxifen-treated women with ER+ tumors drinking 2 or more cups of coffee per day show a significantly reduced risk of early breast cancer recurrence, compared with women with low daily coffee consumptionn summary, this study shows inhibitory effects by caffeine and caffeic acid on breast cancer cell growth. These results are in line with previous epidemiologic reports demonstrating protective roles of coffee constituents and the risk or progression of breast cancer. The present findings enhance the general understanding of how modifiable factors present in our daily diet, such as coffee constituents, may alter ER status, IGFIR levels, and contribute to reduced growth of ER+ and ER− breast cancer cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847429/5Meta-analysisCompared to patients who had consumed less than 2 cups/d of coffee, those who drank ≥ 2 cups/d of coffee before or after diagnosis had a 16% lower risk of death, whereas patients who maintained ≥ 2 cups/d of coffee intake at both periods had a 29% lower risk for all-cause mortality. In addition, we found that additionally adjusting for pre-diagnostic coffee intake attenuated the inverse association between post-diagnostic intake and survival. Given the high correlation of pre- and post-diagnostic coffee intake (r=0.63), these results may suggest that both pre- and post-diagnostic coffee intake are associated with improved CRC survival.In conclusion, our study suggested that higher consumption of coffee after diagnosis was associated with lower CRC-specific and all-cause mortality in patients with stage I to III CRC. Patients who maintain a high level of coffee consumption both before and after diagnosis may have particularly favorable survival. More prospective cohort studies in CRC patients are warranted to confirm our findings and further mechanistic studies are needed to better understand the potential role of higher coffee intake in improving CRC survival.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9798525/5Human study - adjunctIn order to further investigate the role that may caffeine play in risk of progression among men with localized prostate cancer, we evaluated the effect of patient genotype at the rs762551 SNP. We evaluated associations of coffee intake and grade progression among a subset of 346 patients with available genotype data (Table 3). Among patients with an AA (fast metabolizer15) genotype, low to moderate coffee intake (up to 3 cups/day, as compared to 0 cups) was associated with significantly improved PFS (HR 0.36, 95% CI 0.15–0.88, P=0.03). Among patients with the AC/CC (moderate/slow) genotype, higher coffee intake appeared to be associated with increased risk.Unique strengths of our study include robust clinical data regarding prostate cancer surveillance and grade progression in conjunction with dietary assessment. When taken with prior data indicating coffee is associated with lower risk of developing prostate cancer6 and improved outcomes in colorectal cancer patients11, our findings suggest low to moderate coffee consumption is likely safe. We cannot rule out potential increased risk of progression among heavy coffee drinkers and some sensitive groups, such as carriers of the slow caffeine metabolizer genotype
https://euoncology.europeanurology.com/article/S2588-9311(22)00138-9/5Meta-analysis In the group with clinically localized disease, high coffee intake was associated with longer Prostate Cancer Specific Survival (HR 0.66), with comparable results for the group with advanced disease (HR 0.92, 95% CI 0.69–1.23; p = 0.6). High coffee intake was associated with longer PCSS among men with the CYP1A2 AA (HR 0.67) but not the AC/CC genotypeNo associations with OS were observed in subgroup analyses (p > 0.05). Limitations include the nominal statistical significance and residual confounding. Conclusions Coffee intake was associated with longer PCSS among men with a CYP1A2 −163AA (*1F/*1F) genotype, a finding that will require further replication.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622099/5Meta-analysisPatients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 , compared with never drinkers... Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality.In sum, this prospective study of patients with stage III colon cancer, embedded in a randomized clinical trial, demonstrates improved patient outcome with increased consumption of total coffee, caffeinated coffee, and caffeine. Although our observational study does not offer conclusive evidence for causality, our findings potentially inform colon cancer biology and offer further insight into the role of diet and lifestyle in outcome for patients with colon cancer.
https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.150895Human study, Human study - adjunctNinety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1‐40.5). For overall survival postoperative coffee intake emerged as a major factor of hazard reduction in a multivariate analysis (HR = 0.29, 95% CI = 0.12‐0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029)Our results show that consumption of caffeinated coffee is associated with a decreased risk of HCC recurrence and beneficial survival following OLT. Experimental data suggest that such clinical benefits of coffee is associated, at least in part, with the antagonist activity of caffeine on adenosine‐receptor mediated growth‐promoting effects in HCC cells.
https://onlinelibrary.wiley.com/doi/10.1002/ijc.348795Meta-analysisIn the multivariable-adjusted model, [colorectal cancer patients] consuming >4 cups/d of coffee compared with an intake of <2 cups/d was associated with a 29% lower risk of all-cause mortality (HR: 0.71, 95% CI: 0.53, 0.94; Table 2). The association was more pronounced with the intake of 2–4 cups/d of coffee (HR: 0.62, 95%CI: 0.48, 0.81). This was supported by the result from the RCS analysis that suggested a U-shaped association between coffee consumption and all-cause mortality (P-value for nonlinearity <0.001; Figure 2B). Coffee consumption seemed optimal at 3–5 cups/d and with the lowest risk at 4 cups/d (HR: 0.68, 95% CI: 0.53, 0.88). We observed a similar U-shaped association in the 533 never smokers in our study (Figure S1). Components of coffee, especially chlorogenic acids are potent antioxidants that could improve endothelial and vascular function by increasing the availability of nitric oxides,48 which are important for maintaining cardiovascular health.49 Additionally, the inverse association between coffee consumption and all-cause mortality may be partly explained by the potential reduced risk of CRC recurrence with increased coffee consumption. Approximately 20%–30% of CRC patients experience recurrence23, 24 which is an independent risk factor for mortality.50 Notwithstanding, more research is needed to fully understand the specific underlying mechanism by which coffee consumption could improve CRC prognosis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144620/5Meta-analysisHigher post-diagnostic coffee consumption was associated with a lower breast cancer-specific mortality: compared with non-drinkers, >3 cups/day of coffee was associated with a 25% lower risk (hazard ratio (HR) = 0.75) . We also observed a lower all-cause mortality with coffee consumption: compared with non-drinkers, >2 to 3 cups/day was associated with a 24% lower risk (HR = 0.76) and >3 cups/day was associated with a 26% lower risk (HR = 0.74. Post-diagnostic tea consumption was associated with a lower all-cause mortality: compared with non-drinkers, >3 cups/day was associated with a 26% lower risk (HR = 0.74).In conclusion, our findings suggest that coffee consumption after a breast cancer diagnosis may improve both breast cancer-specific and overall survival in a dose-dependent manner. Both regular and decaffeinated coffee appear to contribute to these lower risks. High tea consumption may improve overall survival. Confirmation of these results and investigations into potential mechanisms would be useful. These results add to a body of literature showing general benefits of coffee drinking14,25 and can provide reassurance to breast cancer survivors who are habitual coffee drinkers
https://bmjopen.bmj.com/content/7/5/e0137394.5Meta-analysisIncreased consumption of caffeinated coffee and, to a lesser extent, decaffeinated coffee are associated with reduced risk of HCC, including in pre-existing liver disease. These findings are important given the increasing incidence of HCC globally and its poor prognosis.An extra two cups per day of coffee was associated with a 35% reduction in the risk of HCC (RR 0.65). The inverse association was weaker for cohorts (RR 0.71), which were generally of higher quality than case–control studies (RR 0.53)
https://www.tandfonline.com/doi/full/10.1080/01635581.2015.10047274.5Meta-analysisThe dose-response analysis showed a lower cancer risk decreased by 2.5% (RR = 0.975; 95% CI: 0.957–0.995) for every 2 cups/day increment in coffee consumption. Stratifying by geographic region, there was a statistically significant protective influence of coffee on prostate cancer risk among European populationsIn subgroup analysis of prostate cancer grade, the summary RRs were 0.89 (95% CI: 0.83–0.96) for nonadvanced, 0.82 (95% CI: 0.61–1.10) for advanced and 0.76 (95% CI: 0.55–1.06) for fatal diseases. Our findings suggest that coffee consumption may be associated with a reduced risk of prostate cancer and it also has an inverse association with nonadvanced prostate cancer
https://hrjournal.net/article/view/3989#sec154Human studyWith the decreased incidence of HCC in chronically infected HCV patients and the increase of liver tumor related to metabolic diseases, recommending a moderate coffee intake in these patients could be reasonable. There is no sufficient evidence to prescribe coffee in patients at risk of developing HCC, but moderate daily consumption of coffee should be encouraged in patients who are already doing so. Coffee consumption has proved to be beneficial in reducing the risk of NAFLD and the development of hepatic fibrosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291982/4Human studyAfter the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day. Conclusions: This phase I study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 gliomaAlthough the size of this trial was small, the study did indicate that 52.1% of patients (12 of 23) achieved SD at the end of the first cycle of treatment. Importantly, the estimated median OS was 11.3 months for all patients and was 9.4 months for the 18 patients with grade 4 glioma. Furthermore, the 1-year survival rate was 47.8%, and 2 patients were alive at the cutoff day of February 11, 2022. With respect to the median OS (5.7 to 7.5 months) for patients with recurrent high-grade glioma treated with standard-of-care therapeutics, the median OS was prolonged after CGA treatment. These preliminary results are very encouraging and may aid in providing necessary care for a deadly malignancy.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/26861454Meta-analysisCoffee drinking was inversely associated with mortality, including among those drinking 8 or more cups per day and those with genetic polymorphisms indicating slower or faster caffeine metabolism. These findings suggest the importance of noncaffeine constituents in the coffee-mortality association and provide further reassurance that coffee drinking can be a part of a healthy diet.In this large study of nearly 500 000 people in the United Kingdom, coffee drinking was inversely associated with all-cause mortality, with statistically significant inverse associations observed in participants drinking 1 to 8 or more cups per day. Inverse associations were also observed for ground and instant coffee, although were somewhat weaker for instant coffee, and for cancer and cardiovascular disease mortality, the 2 most common causes of death in the cohort
https://www.nature.com/articles/srep33711#Sec74Meta-analysisOur meta-analysis supports an inverse association between coffee intake and oral, pharynx cancer, liver cancer, colon cancer, prostate cancer, endometrial cancer and melanoma There are several mechanisms attempting to explain this phenomenon. Coffee contains many bioactive components, including caffeine, cafestol, kahweol and chlorogenic acid. Some studies indicate that caffeine can prevent oxidative DNA damage, modify the apoptotic response and reverse the cell cycle checkpoint function
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362645/3.5Meta-analysisGCE [Green Coffee Extract] supplementation had favorable effects on glycemic indices including FBG [glucose] and insulin levels. In terms of lipid profile, GCE supplementation led to a significant reduction in serum TC [cholesterol], particularly in individuals with elevated levels of TC. This suggests GCE as a promising antihyperlipidemic agent since some patients do not achieve cholesterol reduction goals or cannot tolerate statins... We also found a significant favorable effect of GCE on serum levels of TG, LDL, and HDL in some subgroups. The effect was more prominent in women and studies with a long duration of intervention [ >8 weeks in 100mg+ dose]Dose-response analysis demonstrated a significant increment in serum levels of HDL from CGA dosage of 100 mg/day to higher amounts. Moreover, we found a significant non-linear association between CGA dosage and serum TG concentrations. However, the TG-lowering effect of CGA was decreased at a dosage of 500 mg/d and over. The effect of green coffee on lipid profile was also dose-dependent..Therefore, the dosage of CGA is a potential moderator for the beneficial effect of GCE on lipid profile. CGA may exert its lipid-lowering effects through inhibition of the lipids absorption and the formation of cholesterol micelles. Also, CGA is involved in modifying hepatic metabolism of cholesterol and fatty acids by inhibiting pancreatic lipase and hydroxymethyl glutaryl Co-A reductase and increasing the activity of fatty acid beta-oxidation and the expression of peroxisome proliferator-activated receptor-alpha in the liver... higher dosages of more than 500 mg/d CGA is not recommended
https://www.meb.ki.se/biostat/bio1/week2/papers/wilson%20et%20al%20CCC_2013.pdf3.5Meta-analysisIn conclusion, there was a suggestion that regular coffee consumption was associated with lower risk of lethal and high-grade prostate cancer in this population-based case– control study in Sweden. Given the lack of identified modifiable risk factors for prostate cancer, this association is potentially important and should be studied in other populationsRisk of advanced prostate cancer was non-significantly lower among the highest coffee consumers with an adjusted OR of 0.73 (CI 0.41–1.30, p trend = 0.98). Risk of high-grade (Gleason 8–10) prostate cancer was significantly inversely associated with the highest coffee intake, with an OR of 0.50 (0.26–0.98, p trend = 0.13) for high-grade
https://apm.amegroups.org/article/view/65733/html3.5Meta-analysisOverall, the meta-analysis found a negative correlation [lower risk] between coffee intake and breast cancer risk, especially in postmenopausal and European women.Regarding the relationship between coffee intake and breast cancer risk before and after menopause, our meta-analysis showed that coffee intake and breast cancer incidence were negatively correlated in postmenopausal women. The effect of menstrual status on breast cancer risk may be related to interaction between caffeine and free estradiol in premenopausal women
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654648/3Meta-analysisOur results show that both kahweol and cafestol exert their actions on various cancers via inducing apoptosis and inhibiting cell growth. Additionally, kahweol acts by inhibiting cell migration.Kahweol and cafestol, two diterpenes, were found to have a striking role in preventing the progression of several types of cancer, as discussed above. This effect is achieved mainly by inducing apoptosis, alongside cytotoxicity and mitochondrial damage, which are mediated by targeting certain downstream molecules and pathways
https://nutritionj.biomedcentral.com/articles/10.1186/s12937-020-00587-z#3Human studyWe found a significant reducing effect of GCE supplementation on FBG (weighted mean difference (WMD): -2.35, 95% CI: − 3.78, − 0.92 mg/dL, P = 0.001) and serum insulin (WMD: -0.63, 95% CI: − 1.11, − 0.15 μU/L, P = 0.01). With regard to lipid profile, we observed a significant reduction only in serum levels of TC following GCE supplementation in the overall meta-analysis (WMD: -4.51, 95% CI: − 8.39, − 0.64, P = 0.02). However, subgroup analysis showed a significant reduction in serum TG in studies enrolled both genders.GCE supplementation had favorable effects on glycemic indices including FBG and insulin levels. In terms of lipid profile, GCE supplementation led to a significant reduction in serum TC, particularly in individuals with elevated levels of TC. This suggests GCE as a promising antihyperlipidemic agent since some patients do not achieve cholesterol reduction goals or cannot tolerate statins due to adverse effects [61]. We also found a significant favorable effect of GCE on serum levels of TG, LDL, and HDL in some subgroups
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9862908/2.5Human studywe believe that the main results of the present study are of great clinical importance since we have found that this nutraceutical has a number of beneficial effects on lipid, glucose, hepatic and vascular parameters in pre-obesity subjects, which can be easily translated into the everyday clinical practice of our patients with pre-obesity.We can speculate that the strong antilipidemic actions of Altilix® are related to chlorogenic acid, the main phenolic compound in the formulation. In fact, chlorogenic acid has exhibited numerous notable metabolic actions in humans and animals, independent of its antioxidant effects [21]. In particular, chlorogenic acid, probably through its interaction with a surface receptor, exerts a set of metabolic actions such as the activation of phosphorylating enzyme 5′ adenosine monophosphate-activated protein kinase (AMPK), a key metabolic sensor
https://www.clinicalnutritionjournal.com/article/S0261-5614(16)31329-2/fulltext2.5FMD responses to coffee intake was closely paralleled by the appearance of CGA metabolites in plasma, notably 3-, 4- and 5-feruloylquinic acid and ferulic-40-O-sulfate at 1 h and isoferulic-30-O-glucuronide and ferulic-40-O-sulfate at 5 h. Intervention with purified 5-CQA (450 mg) also led to an improvement in FMD response relative to control (0.75 ± 1.31% at 1 h post intervention, p ¼ 0.06) and concomitant appearance of plasma metabolites. Conclusions: Coffee intake acutely improves human vascular function, an effect, in part, mediated by 5- CQA and its physiological metabolites.Our data, emanating from the two clinical trials, suggest that the acute increases in endothelium-dependent dilation following either coffee, or pure CGA may reflect the potential of phenolic metabolites to influence the bioavailability of nitric oxide within the vasculature. The vasoactive effects of coffee consumption are evident at moderate levels of consumption, with efficacy following a Gaussian profile with respect to total phenolic intake
https://examine.com/supplements/green-coffee-extract/N/AAbsorption and dosageStudies using Green Coffee Extract (GCE) tend to be dosed based on their chlorogenic acid content, which in isolation are taken in the 120-300mg range. Based on this, recommended intakes of GCE would be approximately: 1,200-3,000mg for a 10% chlorogenic acid supplement 600-1,500mg for a 20% chlorogenic acid supplement 240-600mg for a 50% chlorogenic acid supplementThe Chlorogenic Acids in Green Coffee Extract are readily absorbed, and they themselves or their metabolites (such as ferulic acid) mediate many of the benefits of Green Coffee Extract. Supplementing Chlorogenic Acid should also, theoretically, confer much of the same benefits as Green Coffee Extract (and vice versa).
https://www.sciencedirect.com/science/article/pii/S0022316622097644?via%3DihubN/AAbsorption and dosageThis study shows that the main CGA compounds present in the green coffee matrix are highly bioavailable in humans. A large inter-individual variation clearly exists in CGA absorption, metabolismChlorogenic acids (CGA) are cinnamic acid derivatives with biological effects mostly related to their antioxidant and antiinflammatory activities...This study shows that the major CGA compounds present in green coffee are highly absorbed and metabolized in humans.
https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.04-2126com1Lab studyWe confirmed that caffeic acid CA suppressed the growth of HepG2 tumor xenografts........significantly reduced liver metastasisThese results confirm the therapeutic potential of the compounds and suggest that the anti-metastatic and anti-tumor effects of CA are mediated through selective suppression of MMP-9
https://www.biorxiv.org/content/10.1101/2020.06.11.146027v2.full1Lab studywe find chlorogenic acid hindered the binding of ANXA2 and actin maybe involved in the impediment of tumor cell cycle and migration. Thus, this work demonstrates that chlorogenic acid, as a binding ligand of ANXA2, decrease the expression of NF-κB downstream anti-apoptotic genes, inhibiting the proliferation of A549 cells in vivo and vitro CGA blocks the interaction between actin and ANXA2. CGA also arrests cell cycle G0/G1 and obstructs migration of cancer cell. Thus, CGA has the potential to become a significant anti-tumor drug especially in the treatment of lung cancer in the future.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757108/1Lab studyThe results demonstrated that CGA could significantly inhibit viability and induce apoptosis in breast cancer cells. Additionally, CGA suppressed the migration and invasion of breast cancer cells by impairing the NF-κB/EMT signaling pathwayFurthermore, CGA significantly slowed tumor growth, prolonged the survival rate and inhibited pulmonary metastasis by increasing the proportion of CD4+ and CD8+ T cells in spleens, thus improving antitumor immunity.
https://www.hindawi.com/journals/ecam/2020/1515081/1RLT-03 [astragalus derivative + cholorogenic acid] inhibited cell viability and induced apoptosis in a dose- and time-dependent manner. In vivo, tumor volume and weight were reduced, and the expression of VEGF, EGF, IL-10, TGF-β, and CD34 was suppressed in the tumor microenvironment, while cell apoptosis was induced. Conclusion. RLT-03 exhibited therapeutic effects against breast cancer by regulating the expression of ligands of receptor tyrosine kinases (RTKs) and inflammatory factors. Thus, RLT-03 represents a potential supplementary HM that can be used in breast cancer therapy.RLT-03 exhibited prominent therapeutic effects on breast cancer mainly via the regulation of cell proliferation, apoptosis, and the tumor-microenvironment through the downregulation of the expression of RTK ligands and inflammatory factors. Thus, RLT-03 represents a useful and an alternative supplementary medicine for the late-stage and poor performance breast cancer patients, who could not tolerate or refuse second-/third-line therapy. The potential therapeutic effects of RLT-03 may be further ascertained in clinical trials.
https://cellmolbiol.org/index.php/CMB/article/view/2367/12781Lab studyCGA blocked the proliferative capacity of NSCLC cells in vitro. Results from the migration assay suggested that CGA also inhibited the migration of A549 cells. Other assays further revealed that CGA strongly and selectively inhibited histone deacetylase 6 (HDAC6) activity and suppressed the activity of matrix metalloproteinase-2 (MMP-2) through decreased expression of Ac-NF-κBTumorigenicity assay showed that CGA also inhibited the proliferation and metabolism of NSCLC in vivo. These results indicate that CGA significantly suppresses the proliferation of NSCLC by regulating the activity of histone deacetylase 6
https://aacrjournals.org/cancerpreventionresearch/article/7/10/1056/50194/Caffeic-Acid-Directly-Targets-ERK1-2-to-Attenuate1Lab studyCaffeic acid topically applied to dorsal mouse skin significantly suppressed tumor incidence and volume in a solar UV (SUV)–induced skin carcinogenesis mouse model. A substantial reduction of phosphorylation in mitogen-activated protein kinase signaling was observed in mice treated with caffeic acid either before or after SUV exposureTaken together, our results suggest that caffeic acid exerts chemopreventive activity against SUV-induced skin carcinogenesis by targeting ERK1 and 2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815948/1Lab studyWe found that Chlorogenic Acid CA functioned as a safe differentiation inducer for solid tumors. After observing the exceptional therapeutic effect and excellent safety by CA in the recurrent high-grade glioma patients in the Phase I study (NCT02728349), CA has been approved by China FDA for Phase II trial (NCT03758014). Our study strongly suggested that “educating” cancer cells, rather than killing them, is a good option for future anticancer therapy. We consider CA as a promising therapeutic agent for cancer.In animal experiments, we showed that CA treatment terminated tumor growth. The detection of the genes/proteins associated with differentiation in tumors from the CA-treated animals revealed a profile identical to that observed in vitro. Through tumor re-implantation, we showed that CA also differentiated cancer stem cells. This inference was based upon the observation that the residual tumor cells from the CA-treated animals largely lost the ability to grow new tumors in vivo
https://www.nature.com/articles/srep390111Lab studyHerein we, for the first time, demonstrated that CHA treatment inhibited anti-inflammatory sate and induced activated macrophage to antitumor pro-inflammatory phenotype, consistent with the inhibition of glioma growth in vitro and in vivo.Taken together, these data support the hypothesis that the in vivo and in vitro antitumor effect of CHA depends on the macrophage polarization. We suggested that CHA is not only a potent inhibitor of M2 activation but also an enhancer for M1 activation.
https://www.spandidos-publications.com/10.3892/ijo.2016.37271Lab study These results indicate that kahweol may inhibit cell proliferation and induce apoptosis due to BTF3 via the ERK signaling pathway. Thus, kahweol might be a promising chemotherapeutic agent in the treatment of patients with NSCLC.In addition, kahweol both induced Bax and reduced Bcl-2 and Bcl-xL expression while also activating caspase-3 and PARP, which suggests that kahweol suppressed BTF3 expression and ultimately led to apoptotic cell death
https://www.sciencedirect.com/science/article/pii/S0014579304007082#SEC11Lab studyThe results in this study link the effects of kahweol and cafestol to the inhibition of PGE2 production. With regard to PGE2 production, it was shown that kahweol and cafestol inhibit the LPS-activated induction of COX-2 in the macrophages.It was found that the simultaneous treatment of either kahweol or cafestol with LPS significantly inhibited COX-2 mRNA and protein expression (Fig. 3). Kahweol had a more potent inhibitory effect on PGE2 production and the COX-2 expression than cafestol.
https://www.frontiersin.org/articles/10.3389/fcell.2020.585987/full#h31Lab studyWe found that caffeic acid effectively suppresses self-renewal capacity, stem-like characteristics, and migratory capacity of CD44+ and CD133+ colorectal CSCs in vitro and in vivoTo the best of our knowledge, this is the first study demonstrating that caffeic acid effectively targets colorectal CSC populations by inhibiting the growth and/or self-renewal capacity of colorectal CSCs through PI3K/Akt signaling in vitro and in vivo.
https://jpet.aspetjournals.org/content/384/2/2541Lab studyIncreasing evidence has testified that CA has an anti-invasive effect on a variety of cancers. In hepatocellular carcinoma, CA has been proven to be one of the chemical entities in coffee inhibiting hepatoma invasion Moreover, CA could inhibit tumor growth and xenograft tumor EMT in vivo. CA has a good therapeutic effect and is expected to be a potential drug for the treatment of metastatic breast cancer.
https://e-century.us/files/ijcem/12/5/ijcem0078541.pdf1Lab studyAdministration of CGA to mice bearing tumor cell-implanted xenografts also inhibited tumor growth in vivo. Collectively, these data suggest that the mTORC2/F-actin pathway is involved in CGA-induced tumor suppression. CGA might have the potential to become an anti-cancer agent.Here, we show for the first time that CGA could lead to deceased mTORC2 activation, which was demonstrated by less phosphorylation of mTORC2 and downstream pPKCα and pAkt signals
https://www.sciencedirect.com/science/article/pii/S0753332219352242?via%3Dihub#sec00601Lab studyIn this study, we confirmed the inhibition of proliferation by CGA in ESCC cells, as well as the reduction of ESCC xenograft volume by CGA in vivo. In addition, CGA also suppressed both the migration and invasion of ESCC cells in vitro. Together, our initial findings demonstrate that CGA suppresses ESCC progression, downregulates the expression of BMI1 and SOX2, and provide an anti-tumor candidate for ESCC therapy.
https://academic.oup.com/carcin/article/32/6/921/2463427#859190611Lab studyCoffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPKCoffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639050/1Lab studyWe found that caffeic acid inhibited UVB-induced COX-2 upregulation at the transcriptional level by suppressing COX-2 promoter activity, which resulted from the inhibition of AP-1 and NF-κB transactivationIn vivo data from mouse skin also supported the idea that caffeic acid suppressed UVB-induced COX-2 expression by blocking Fyn kinase activity. These results suggested that this compound could act as a potent chemopreventive agent against skin cancer.
https://www.sciencedirect.com/science/article/abs/pii/S0955286315002314?via%3Dihub1Lab studyOur data demonstrate that coffee inhibits NF-κB activity in PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription of genes related to prostate cancer and inflammation. Our results are the first to suggest mechanistic links between coffee consumption and prostate cancer in an experimental mouse model.In vivo imaging revealed a 31% lower NF-κB-luciferase activation in the xenografts of the mice receiving 5% coffee compared to control mice. Interestingly, we observed major changes in gene expression in the PC3 cells in xenografts
https://www.sciencedirect.com/science/article/pii/S0022316622144597?via%3DihubN/AAbsorption and dosageThus, one third of chlorogenic acid and almost all of the caffeic acid were absorbed in the small intestine of humans. This implies that part of chlorogenic acid from foods will enter into the blood circulationWe cannot exclude that part of the supplements were lost somewhere in the gastrointestinal tract; therefore, the absorption values we found in this study should be regarded as maximum absorption values rather than as fixed absorption values
https://globaljournals.org/GJMR_Volume11/4-Evaluation-of-Roasting-and-Brewing-effect-on-Antinutritional.pdfN/AAbsorption and dosageAs the roasting temperature increases there was a significant fall in both cafestol and kahweol profiles. Accordingly in full city roast there was ~56% reduction in cafestol and 61% reduction in kahweol compared to normal roasted beansThe higher levels of cafestol and kahweol in Turkish and French press coffee in our study was in accordance with earlier report [7] wherein, both the diterpenes per cup were at higher level in boiled Scandinavian coffee (7.2 mg each of cafestol & kahweol ) and Turkish coffee (5.3 mg of cafestol & 5.4 mg of kahweol) respectively

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