Resveratrol rapidly activate mitogen-activated protein kinase (MAPK) in a MEK-1, Src, matrix metalloproteinase, and epidermal growth factor receptor in a dependent manner. It activates MAPK and endothelial nitric-oxide synthase (eNOS) at nanomolar concentrations (i.e., magnitude less than that required for ER genomic activity) and at concentrations possibly/transiently achieved in serum following oral red wine consumption 147. Additionally, resveratrol consumption at modest doses result in a life span increase in 1-year old mice. However, when mice consumed larger resveratrol doses (1800 mg/kg), animals were shown to die within 3–4 months 148. Studies on steady-state pharmacokinetics and tolerability of 2000 mg trans-resveratrol, administered twice daily with food, quercetin and alcohol (ethanol) showed that trans-resveratrol was well-tolerated by healthy subjects, although diarrhea was frequently observed 149.
Study design and subjects
We think that the enhancement of CAT activities may not come from high concentration of ethanol, but rather from the compensatory improvement of antioxidant capacity after the intervention with low-concentration ethanol in the early stage. Firstly, antioxidants exhibit a threshold effect, where excess levels may exhibit pro-oxidant properties. Yet, OBS is defined under the assumption of a linear relationship between all components and oxidative stress, and its assessment via questionnaires is prone to recall and selection biases in reporting nutrient intake. Secondly, as this study was conducted in the US population, the racial universality of our findings remains to be further validated. Thirdly, despite constructing multivariate logistic regression models and conducting subgroup and sensitivity analyses to mitigate confounding factors, residual confounding effects cannot be entirely ruled out. Lastly, as a cross-sectional study, this research cannot establish a causal relationship between OBS and CKD, highlighting the need for more prospective studies in this area.
However, adjusting the confounding factors indicated that occasional drinking as compared to nondrinking significantly increased the odds of stage 3 and 4 CKD prevalence as compared to stage 1 CKD prevalence. In addition to the association of alcohol consumption with different CKD stages, it was revealed that factors such as aging, history of cerebrovascular disease, and increased LDL and Cr can increase the odds of CKD prevalence at higher stages. Overall, all the studies we found point towards elevated risk of primary hypertension development among heavy drinkers regardless of gender. The risk among those who consume low and moderate amounts of alcohol may not be significantly elevated. It should be noted that not all the aforementioned findings can be generalized to the total population as the patient sample that was used was limited, either geographically or age-wise. In order to further our understanding of the issue, it would be essential to do more research on the pathophysiology of alcohol-induced hypertension.
- Since aging, metabolic diseases, and hypertension impair kidney function, they can also influence the effect of ethanol on the kidneys.
- When experts talk about one drink, they are talking about one 12-ounce bottle of beer, one glass of wine (5 ounces), or one shot (1.5 ounces) of “hard liquor.” Always consult your healthcare provider to determine what’s safe for you.
- In this review, we focused on the effect of ethyl alcohol on the kidneys and the effect of drinking on patients with CKD, and summarized the clinical and experimental studies.
- Na+-K+-ATPase present on the proximal tubular epithelial membrane is important for tubular reabsorption.
- This self-report is susceptible to under-reporting and underestimates the patients’ alcohol consumption 12,13,117.
Medical Disclaimer:
We conducted a cross-sectional analysis involving 25,118 participants from the NHANES database. Our findings revealed a negative association between OBS and the risk of CKD, with this relationship remaining consistent across subgroup and sensitivity analyses. Furthermore, we observed a more pronounced correlation between OBS and CKD in the subgroup of participants aged over 60 years. Collectively, our study provides preliminary evidence for the exploration of the correlation between OBS and CKD, offering novel insights for future clinical and basic research endeavors.
Lifestyle Choices to Prevent Kidney Stones
Ethyl alcohol and water are the main ingredients of alcohol beverages, but we cannot ignore other bioactivators in liquors, such as polyphenols. Moreover, alcohol-induced renal tubular dysfunction is also reflected in vitamin reabsorption disorders. Subramanian et al. proved that chronic alcohol consumption can significantly inhibit carrier-mediated thiamin and biotin transport across the renal brush border membrane and basolateral membrane 54,55. Diagrammatic representation of resveratrol biphasic activity and gene expression modulation. At nanomolar 124 doses, resveratrol acts as a potent antioxidant, while at micromolar (μM) range, it interacts as agonist or antagonist exhibiting cell proliferation/cytoprotective responses or cytostatic/apoptotic effects, respectively.
2 Association between OBS and CKD
Among the isolated resveratrol oligomers, vitisin A and heyneanol A have been reported for better dose-dependent inhibitory potential compared with standard inhibitor (galantamine) on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity 17,37. Resveratrol is also able to improve rat motor abilities and to deactivate neuroinflammatory response following intracerebral hemorrhage. Further, we assessed alcohol consumption, SUA, and renal function at a single time point and did not conduct follow‐up evaluations to determine clinical impact.
- Furthermore, alcohol has an anti-inflammatory effect, with increased serum interleukin-10 levels and decreased serum interleukin-16 levels 20.
- If you fall into any of these categories, avoiding alcohol, or closely monitoring your use, may be your best bet.
- Thirdly, despite constructing multivariate logistic regression models and conducting subgroup and sensitivity analyses to mitigate confounding factors, residual confounding effects cannot be entirely ruled out.
- However, as alcohol consumption can lead to adverse events, such as hypertension, cerebral hemorrhage, alcohol addiction, and tendencies toward violence, clinicians should not advise non-drinkers to start drinking.
- Second, the proteinuria detection and diagnosis of CKD can also affect the credibility of the conclusion.
- Indeed, resveratrol anticancer properties have been confirmed by many in vitro and in vivo studies, which shows that resveratrol is able to inhibit all carcinogenesis stages (e.g., initiation, promotion and progression).
In summary, there is no exact evidence that alcohol consumption aggravates the state of CKD or increases all-cause mortality in alcohol consumption can be a double-edged sword for chronic kidney disease patients pmc CKD, and the protective effect of abstinence on such patients is unclear. Although many studies stated that people should not start drinking for any reason, and alcohol consumption can increase disease risk 125, we also cite many studies demonstrating the protective effects of light-to-moderate alcohol consumption in our review. Although there has long been controversy about the renal-protective effect of alcohol consumption on kidney injury, the renal-protective effects of polyphenols and other bioactivators from wine has been demonstrated in many studies 15,95,97,101–103. These include anthocyanins, which are the main polyphenols in red grapes, and resveratrol, which is the most famous polyphenolic compound found in red wine 104.
Therefore, the effect of ethanol on renal antioxidant capacity varies with the concentration of ethanol and the duration of stimulation. In general, ethanol causes oxidative stress-related damage in the kidneys, but sometimes, in some conditions, it also improves the antioxidant capacity of the renal cells. Unfortunately, we only know that low-concentration ethanol can improve renal antioxidant capacity, but the exact dose and period are still unclear. Pterostilbene is a methoxylated derivative of resveratrol that showed antibacterial activity against drug-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) superior of pterostilbene compared to resveratrol (8~16-fold). Pterostilbene anti-MRSA potency was related to bacterial membrane leakage, chaperone protein downregulation, and ribosomal protein upregulation and can be topically applied for treatment of skin MRSA infection bearing it less toxicity to mammalian cells 32. From another point of view, reactive oxygen species (ROS), superoxide, peroxide, and hydroxyl radicals are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents.
Influence of sex, age, primary diseases and other confounding factors
It may lead to interactions with various cytochrome P450 (CYP), especially when taken at high doses 150. Resveratrol has been reported to inhibit CYP3A4 activity, in vitro 151 and in healthy volunteers 152. Therefore, high resveratrol intakes even in through form of supplements with additional medications could potentially reduce drugs metabolic clearance that undergo extensive first-pass CYP3A4 metabolism, hence increasing both bioavailability and toxicity risk of these drugs.
The National Health Interview Survey selected participants while using a multistage stratified systematic sampling design. Participant information, including education, income, marriage status, and lifestyle behaviors, were obtained during in-person interviews. The National Health Insurance research database comprises medical information of nearly 99% of Taiwanese people, including ambulatory and inpatient care. Kaartinen et al. found that an abnormal immunoreaction may be related to acetaldehyde, the first metabolite of ethanol, which can form covalent adducts with different proteins to activate the immune response49. Resveratrol is a nutraceutical belonging to stilbenoid group, widely distributed in the plant kingdom and with several therapeutic effects.
Some studies found that ethanol has an influence on renal damage, such as apoptosis and epithelial mesenchymal transdifferentiation. Nesreen and Sayed discovered that alcohol consumption significantly increased renal caspase3, caspase8, and caspase9 activity, and ethanol toxicity can increase the ratios of Bax and Bcl-2 in kidney tissues compared to a control group 24,25. This indicates that long-term ethyl alcohol consumption can activate both intrinsic and extrinsic pathways of apoptosis in the kidneys (Figure 1).
Contrarily, at physiological concentrations, resveratrol induces vasodilation, and consequently decreases hypertension and cardiovascular diseases risk 79. On the other hand, these results have also confirmed the uses of Polygonum cuspidatum as a resveratrol source to treat and to prevent hyperlipidemia and arteriosclerosis in traditional chinese medicine 80,81,82. Overall, the cardiovascular protective effect of resveratrol have been linked to multiple molecular targets and might be useful to the development of novel therapy for atherosclerosis, metabolic syndrome, ischemia/reperfusion, and heart failure 83.
