Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human

Abstract

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

The Protective Effects of Ganoderic Acids from Ganoderma lucidum Fruiting Body on Alcoholic Liver Injury and Intestinal Microflora Disturbance in Mice with Excessive Alcohol Intake

“…The result was consistent with the previous report that ethanol has been shown to increase fecal pH and disrupt gut microbiota homeostasis [ 34 ]. Moreover, Lactobacillus and Bifidobacterium encode ADH and ALDH to mediate the metabolism of ethanol and acetaldehyde, respectively, reducing the accumulation of acetaldehyde in the intestinal tract, which can improve the intestinal barrier function, showing a protective action on the development of alcohol-induced liver injury in mice [ 36 ]. On the other hand, oral administration of a high dose of GA markedly increased the relative proportion of producers of SCFAs in mice with excessive drinking, which perform the functions of mucoprotection, immune hemostasis and metabolism, including Faecalibaculum , Bifidobacterium , unclassified_c_Clostridia , Ruminiclostridium , unclassified_o_Coriobacteriales and Christensenellaceae_R-7_group , which are positively correlated with acetic acid and increase total SCFAs production [ 37 , 38 ].…”

The efficacy and tolerability of pharmacologically active interventions for alcohol‐induced hangover symptomatology: a systematic review of the evidence from randomised placebo‐controlled trials

“…For example, those interventions examining agents requiring 14 or more days of use before the onset of hangover symptoms (e.g. Duolac ProAP4 [14]) may not appeal to individuals who are unable to accurately predict in advance when they are likely to consume excessive alcohol. Concerns are often raised that the pursuit of efficacious hangover remedies may lead people to be more likely to consume excessive amounts of alcohol [30, 31] and ultimately perpetuate development of alcohol‐related harm.…”

“…We implemented robust methods to conduct the review, using a broad search strategy and a pre-defined protocol to capture evidence from RCTs. This is also the first systematic review in the treatment and prevention of alcohol-induced hangover to use GRADE methodology to assess the quality of the evidence base and the strength of resultant recommen- ProAP4 [14]) may not appeal to individuals who are unable to accurately predict in advance when they are likely to consume excessive alcohol. Concerns are often raised that the pursuit of efficacious hangover remedies may lead people to be more likely to consume excessive amounts of alcohol [30,31] and ultimately perpetuate development of alcohol-related harm.…”

“…Seven studies reported the number of AEs [22][23][24][25][26][27][28]; there were no statistically significant differences in the number of reported AEs attributed to intervention or placebo across all studies. Five studies reported the number of SAEs [14,22,23,25,27]; there were no reported SAEs in any included study. All results were of low or very low quality according to GRADE.…”

“…Although two previous systematic reviews have examined the evidence base for hangover treatment and prevention [11,12], they have been narratively reported, make no attempt to quantitatively synthesise and compare data across interventions and are restricted to studies conducted over specific time periods. Numerous trials have also been conducted since publication of the most recent systematic review, therefore, the current available evidence syntheses do not consider the totality of the evidence base [13,14], nor do they compare all studied interventions using quantitative techniques. When this is considered alongside the myriad anecdotal reports of efficacious therapies available in print and online media [15], a robust up to date synthesis of the literature is warranted to provide professionals and the public with accurate information as to what, if any, pharmacologically active interventions are evidence-based options.…”