Compendium of the most significant studies with reference to properties, intake, effects.

Hooper Marosek SE, Antharam V, Dowlatshahi K. Quantitative Analysis of the Acetic Acid Content in Substances Used by Athletes for the Possible Prevention and Alleviation of Exercise-Associated Muscle Cramps. J Strength Cond Res. 2020 Jun;34(6):1539-1546. doi: 10.1519/JSC.0000000000003595. 

Abstract. Athletes regularly consume commercially available food and sports shot products, carbohydrate beverages, and water to improve their physical exertion and to possibly prevent or relieve exercise-associated muscle cramps (EAMCs)-often experienced during practice, training, or competition. Acetic acid, a component of interest within these products, has been recognized for its potential role in cramp reduction. Acetic acid is postulated to mitigate cramping by decreasing alpha motor neuron activity through oropharyngeal stimulation and inhibitory neurotransmitter production, while aiding in the role acetylcholine plays in muscle contraction and relaxation. The purpose of this research is to analytically assess the most viable sources of acetic acid from substances that athletes ingest before or when experiencing these cramps. The range of samples investigated were based on their widespread use in the athletic world: dill and sweet pickle juices, yellow mustard, sweet relish, apple cider vinegar, Hot Shot, PJ Shot, PJ Sport, E-Lyte Sport, Powerade, Gatorade, Smartwater, and Propel (with electrolytes). As hypothesized, pH and enzymatic assay or spectroscopic analyses revealed that yellow mustard, sweet relish, all pickle juices, and the pickle juice products were composed of moderate amounts of acetic acid. Based on established studies resulting in EAMC relief, acetic acid consumption, and the appropriate serving size, the yellow mustard, PJ Shot, and all pickle juices would be the most practical and palatable sources of acetic acid for strength and conditioning professionals to recommend that athletes consume for the possible prevention or alleviation of muscle cramps.

Trček J, Mira NP, Jarboe LR. Adaptation and tolerance of bacteria against acetic acid. Appl Microbiol Biotechnol. 2015 Aug;99(15):6215-29. doi: 10.1007/s00253-015-6762-3. 

Abstract. Acetic acid is a weak organic acid exerting a toxic effect to most microorganisms at concentrations as low as 0.5 wt%. This toxic effect results mostly from acetic acid dissociation inside microbial cells, causing a decrease of intracellular pH and metabolic disturbance by the anion, among other deleterious effects. These microbial inhibition mechanisms enable acetic acid to be used as a preservative, although its usefulness is limited by the emergence of highly tolerant spoilage strains. Several biotechnological processes are also inhibited by the accumulation of acetic acid in the growth medium including production of bioethanol from lignocellulosics, wine making, and microbe-based production of acetic acid itself. To design better preservation strategies based on acetic acid and to improve the robustness of industrial biotechnological processes limited by this acid's toxicity, it is essential to deepen the understanding of the underlying toxicity mechanisms. In this sense, adaptive responses that improve tolerance to acetic acid have been well studied in Escherichia coli and Saccharomyces cerevisiae. Strains highly tolerant to acetic acid, either isolated from natural environments or specifically engineered for this effect, represent a unique reservoir of information that could increase our understanding of acetic acid tolerance and contribute to the design of additional tolerance mechanisms. In this article, the mechanisms underlying the acetic acid tolerance exhibited by several bacterial strains are reviewed, with emphasis on the knowledge gathered in acetic acid bacteria and E. coli. A comparison of how these bacterial adaptive responses to acetic acid stress fit to those described in the yeast Saccharomyces cerevisiae is also performed. A systematic comparison of the similarities and dissimilarities of the ways by which different microbial systems surpass the deleterious effects of acetic acid toxicity has not been performed so far, although such exchange of knowledge can open the door to the design of novel approaches aiming the development of acetic acid-tolerant strains with increased industrial robustness in a synthetic biology perspective.

Gullo M, Giudici P. Acetic acid bacteria in traditional balsamic vinegar: phenotypic traits relevant for starter cultures selection. Int J Food Microbiol. 2008 Jun 30;125(1):46-53. doi: 10.1016/j.ijfoodmicro.2007.11.076. 

Abstract. This review focuses on acetic acid bacteria in traditional balsamic vinegar process. Although several studies are available on acetic acid bacteria ecology, metabolism and nutritional requirements, their activity as well as their technological traits in homemade vinegars as traditional balsamic vinegar is not well known. The basic technology to oxidise cooked grape must to produce traditional balsamic vinegar is performed by the so called "seed-vinegar" that is a microbiologically undefined starter culture obtained from spontaneous acetification of previous raw material. Selected starter cultures are the main technological improvement in order to innovate traditional balsamic vinegar production but until now they are rarely applied. To develop acetic acid bacteria starter cultures, selection criteria have to take in account composition of raw material, acetic acid bacteria metabolic activities, applied technology and desired characteristics of the final product. For traditional balsamic vinegar, significative phenotypical traits of acetic acid bacteria have been highlighted. Basic traits are: ethanol preferred and efficient oxidation, fast rate of acetic acid production, tolerance to high concentration of acetic acid, no overoxidation and low pH resistance. Specific traits are tolerance to high sugar concentration and to a wide temperature range. Gluconacetobacter europaeus and Acetobacter malorum strains can be evaluated to develop selected starter cultures since they show one or more suitable characters.

Liao SC, Chen KS, Chien JL, Chen SC, Lin WL. Acetic-Acid Plasma-Polymerization on Polymeric Substrates for Biomedical Application. Nanomaterials (Basel). 2019 Jun 28;9(7):941. doi: 10.3390/nano9070941. 

Abstract. Cold plasma is an emerging technology offering many potential applications for regenerative medicine or tissue engineering. This study focused on the characterization of the carboxylic acid functional groups deposited on polymeric substrates using a plasma polymerization process with an acetic acid precursor. The acetic acid precursor contains oxygen and hydrocarbon that, when introduced to a plasma state, forms the polylactide-like film on the substrates. In this study, polymeric substrates were modified by depositing acetic acid plasma film on the surface to improve hydrophilic quality and biocompatibility. The experimental results that of electron spectroscopy for chemical analysis (ESCA) to show for acetic acid film, three peaks corresponding to the C-C group (285.0 eV), C-O group (286.6 eV), and C=O group (288.7 eV) were observed. The resulting of those indicated that appropriate acetic acid plasma treatment could increase the polar components on the surface of substrates to improve the hydrophilicity. In addition, in vitro cell culture studies showed that the embryonic stem (ES) cell adhesion on the acetic acid plasma-treated polymeric substrates is better than the untreated. Such acetic acid film performance makes it become a promising candidate as the surface coating layer on polymeric substrates for biomedical application.

Yamashita H. Biological Function of Acetic Acid-Improvement in Obesity and Glucose Tolerance by Acetic Acid in Type 2 Diabetic Rats. Crit Rev Food Sci Nutr. 2016 Jul 29;56 Suppl 1:S171-5. doi: 10.1080/10408398.2015.1045966. 

Abstract. Fatty acids derived from adipose tissue are oxidized by β-oxidation to form ketone bodies as final products under the starving condition. Previously, we found that free acetic acid was formed concomitantly with the production of ketone bodies in isolated rat liver perfusion, and mitochondrial acetyl CoA hydrolase was appeared to be involved with the acetic acid production. It was revealed that acetic acid was formed as a final product of enhanced β-oxidation of fatty acids and utilized as a fuel in extrahepatic tissues under the starving condition. Under the fed condition, β-oxidation is suppressed and acetic acid production is decreased. When acetic acid was taken daily by obesity-linked type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats under the fed condition, it protected OLETF rats against obesity. Furthermore, acetic acid contributed to protect from the accumulation of lipid in the liver as well as abdominal fat in OLETF rats. Transcripts of lipogenic genes in the liver were decreased, while transcripts of myoglobin and Glut4 genes in abdominal muscles were increased in the acetic acid-administered OLETF rats. It is indicated that exogenously administered acetic acid would have effects on lipid metabolism in both the liver and the skeletal muscles, and have function that works against obesity and obesity-linked type 2 diabetes.

Martín-Espejo JL, Gandara-Loe J, Odriozola JA, Reina TR, Pastor-Pérez L. Sustainable routes for acetic acid production: Traditional processes vs a low-carbon, biogas-based strategy. Sci Total Environ. 2022 Sep 20;840:156663. doi: 10.1016/j.scitotenv.2022.156663. 

Abstract. The conversion of biogas, mainly formed of CO2 and CH4, into high-value platform chemicals is increasing attention in a context of low-carbon societies. In this new paradigm, acetic acid (AA) is deemed as an interesting product for the chemical industry. Herein we present a fresh overview of the current manufacturing approaches, compared to potential low-carbon alternatives. The use of biogas as primary feedstock to produce acetic acid is an auspicious alternative, representing a step-ahead on carbon-neutral industrial processes. Within the spirit of a circular economy, we propose and analyse a new BIO-strategy with two noteworthy pathways to potentially lower the environmental impact. The generation of syngas via dry reforming (DRM) combined with CO2 utilisation offers a way to produce acetic acid in a two-step approach (BIO-Indirect route), replacing the conventional, petroleum-derived steam reforming process. The most recent advances on catalyst design and technology are discussed. On the other hand, the BIO-Direct route offers a ground-breaking, atom-efficient way to directly generate acetic acid from biogas. Nevertheless, due to thermodynamic restrictions, the use of plasma technology is needed to directly produce acetic acid. This very promising approach is still in an early stage. Particularly, progress in catalyst design is mandatory to enable low-carbon routes for acetic acid production. Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

La China S, Zanichelli G, De Vero L, Gullo M. Oxidative fermentations and exopolysaccharides production by acetic acid bacteria: a mini review. Biotechnol Lett. 2018 Oct;40(9-10):1289-1302. doi: 10.1007/s10529-018-2591-7.

Abstract. Acetic acid bacteria are versatile organisms converting a number of carbon sources into biomolecules of industrial interest. Such properties, together with the need to limit chemical syntheses in favor of more sustainable biological processes, make acetic acid bacteria appropriate organisms for food, chemical, medical, pharmaceutical and engineering applications. At current, well-established bioprocesses by acetic acid bacteria are those derived from the oxidative pathways that lead to organic acids, ketones and sugar derivates. Whereas emerging applications include biopolymers, such as bacterial cellulose and fructans, which are getting an increasing interest for the biotechnological industry. However, considering the industrial demand of high performing bioprocesses, the production yield of metabolites obtained by acetic acid bacteria, is still not satisfying. In this paper we review the major acetic acid bacteria industrial applications, considering the current status of bioprocesses. We will also describe new biotechnological advances in order to optimize the industrial production, offering also an overview on future directions.

Terasaki M, Ito H, Kurokawa H, Tamura M, Okabe S, Matsui H, Hyodo I. Acetic acid is an oxidative stressor in gastric cancer cells. J Clin Biochem Nutr. 2018 Jul;63(1):36-41. doi: 10.3164/jcbn.17-49. 

Abstract. Acetic acid can cause cellular injury. We previously reported that acetic acid induces cancer cell-selective death in rat gastric cells. However, the mechanism is unclear. Generally, cancer cells are more sensitive to reactive oxygen species than normal cells. Accordingly, in this study, we investigated the involvement of oxidative stress in cancer cell-selective death by acetic acid using normal gastric mucosal cells and cancerous gastric mucosal cells. The cancer cell-selective death was induced at the concentration of 2-5 µM acetic acid. Cancerous gastric mucosal cells had increased expression of monocarboxylic transporter 1 and high uptake of acetic acid, compared to normal gastric mucosal cells. The exposure of cancerous gastric mucosal cells to acetic acid enhanced production of reactive oxygen species and expression of monocarboxylic transporter 1, and induced apoptosis. In contrast, acetic acid showed minor effects in normal gastric mucosal cells. These results indicate that acetic acid induced cancer cell-selective death in gastric cells through a mechanism involving oxidative stress.

Okabe S, Amagase K. An overview of acetic acid ulcer models--the history and state of the art of peptic ulcer research. Biol Pharm Bull. 2005 Aug;28(8):1321-41. doi: 10.1248/bpb.28.1321.

Abstract. Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers >100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.

Maruta H, Abe R, Yamashita H. Effect of Long-Term Supplementation with Acetic Acid on the Skeletal Muscle of Aging Sprague Dawley Rats. Int J Mol Sci. 2022 Apr 23;23(9):4691. doi: 10.3390/ijms23094691. 

Abstract. Mitochondrial function in skeletal muscle, which plays an essential role in oxidative capacity and physical activity, declines with aging. Acetic acid activates AMP-activated protein kinase (AMPK), which plays a key role in the regulation of whole-body energy by phosphorylating key metabolic enzymes in both biosynthetic and oxidative pathways and stimulates gene expression associated with slow-twitch fibers and mitochondria in skeletal muscle cells. In this study, we investigate whether long-term supplementation with acetic acid improves age-related changes in the skeletal muscle of aging rats in association with the activation of AMPK. Male Sprague Dawley (SD) rats were administered acetic acid orally from 37 to 56 weeks of age. Long-term supplementation with acetic acid decreased the expression of atrophy-related genes, such as atrogin-1, muscle RING-finger protein-1 (MuRF1), and transforming growth factor beta (TGF-β), activated AMPK, and affected the proliferation of mitochondria and type I fiber-related molecules in muscles. The findings suggest that acetic acid exhibits an anti-aging function in the skeletal muscles of aging rats.

Doles W, Wilkerson G, Morrison S, Richmond RG. Glacial Acetic Acid Adverse Events: Case Reports and Review of the Literature. Hosp Pharm. 2015 Apr;50(4):304-9. doi: 10.1310/hpj5004-304. 

Abstract. Glacial acetic acid is a dangerous chemical that has been associated with several adverse drug events involving patients over recent years. When diluted to the proper concentration, acetic acid solutions have a variety of medicinal uses. Unfortunately, despite warnings, the improper dilution of concentrated glacial acetic acid has resulted in severe burns and other related morbidities. We report on 2 additional case reports of adverse drug events involving glacial acetic acid as well as a review of the literature. A summary of published case reports is provided, including the intended and actual concentration of glacial acetic acid involved, the indication for use, degree of exposure, and resultant outcome. Strategies that have been recommended to improve patient safety are summarized within the context of the key elements of the medication use process.