Has Anyone Tried Sodium Acetate ? (for SIBO?)

[Amazoniac]

Yes I'm curious, for sure. Why would the japanese mix sugar with vinegar so ignorantly, it's so unlike them. Interesting you mention that, I do wonder if propionate is not overproduced in my body. It could help explain why carnitines seem to help (besides stuff regarding astrocytes). Its metabolism is problematic.

Then again:
Effects of SCFA on the DNA methylation pattern of adiponectin and resistin in high-fat-diet-induced obese male mice. - PubMed - NCBI

Guru, the thought of seasoned vinegar occurred to me as well, and it got me wondering how traditional it is.
- Rice - Wikipedia
- History of sugar - Wikipedia

If I come across something relevant to the enzymes, I'll post.

For now, what could also be concerning is the possibility of enhancement of iron adsorqtion (as it happens with other acids), although the effect might differ when it's neutralized.
- Effect of Vinegar on Absorption of Iron in Rats (日本語)

 

[Amazoniac]

This is such a special toxin.

In terms of effects, I was wondering if it could involve thiamide, an aesoteric bypass (described in other circumstances) to the thiamide-dependent reaction of pyruvate with SH-coA, yielding acetyl-coA, where the hydrogen iod is replaced; in this case it would be acetate instead of pyruvate.
Acetyl-CoA - Wikipedia
Acetyl-CoA synthetase - Wikipedia

Even though the amount isn't great in relation to what's obtained from carbohydrates, it concentrates in the liver, so it's a good suspect to be reaping its benefits and the positive effects stemming from there.

It's possible to be affecting the lining of the intestines. Manipulation of these acids can control proliferation, and if I remember it right, I read somewhere that acetate can induce tissue overgrowth. This could be desirable if a barrier is compromised, it's similar to what has been claimed to occur when poison/"vitamin" A is cleared from the body.

Acetylation is also something to consider, for some reason is neglected compared to the attention that sulfatization and glucuronidization get. Here they provide a table for the enzymes that should be functioning and the cofactors required:
- Drug metabolism - Wikipedia

Mito pointed out that the acetyl group in aspirin is involved in resolution of inflammation.
- Aspirin - Wikipedia

One more aspect to consider:
- Acetate reduces PGE2 release and modulates phospholipase and cyclooxygenase levels in neuroglia stimulated with lipopolysaccharide

--
These are related to the first link from post #81:
- Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation
- Neuroglial Mechanisms Involved In The Anti-Inflammatory Effect Of Acetate Supplementation

 

[Elchapchapchapo]

Hey so there are 3 acids like sodium acetate. I can’t remember where I saw it. I’ll have to dig around and find it. But anyway one of the other ones is butrayte

 

[Amazoniac]

- High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice

"In the present study, we aimed to investigate whether dietary fiber or acetate supplementation, through changes in the gut microbiota, prevents the development of hypertension and associated renal and cardiac fibrosis in the deoxycorticosterone acetate (DOCA)–salt model. Last, we also determined the transcriptome involved in the cross-talk between the gut, kidney, and heart."

Spoiler: Figure 1. The effect of deoxycorticosterone acetate (DOCA)–salt, a diet rich in fiber and acetate supplementation, in the gut microbiome.

"Percentage of total bacteria presented at the (B) phyla and (C) family level. D, Mice fed a high-fiber diet or acetate had a significantly higher percentage of acetate-producing bacteria (P<0.0001). E, Ratio of Firmicutes to Bacteroidetes (F/B), as a marker of gut dysbiosis, is lower in mice fed high fiber or acetate, independently of surgical state (P<0.0001). One-way ANOVA with a Tukey adjustment for multiple comparison was used."

Spoiler: Figure 3. Acetate improves renal fibrosis in deoxycorticosterone acetate (DOCA)–salt model.

Spoiler: Figure 4. High fiber diet and acetate reduce cardiac fibrosis in deoxycorticosterone acetate (DOCA)–salt model.

Read it for more (cool) details.
It's interesting that acetate was ingested and crap was collected from the colon showing those differences.
Since the form was magnesium acetate, I wonder how much the mineral played a rôle in terms of prevention of fibrosas.

 

[Amazoniac]

Surprise, surprise: sugar is toxic. You know that it was a short experiment because otherwise the word used would be 'fatal'.

- A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice

"Western-style diets have been implicated in triggering inflammatory bowel disease activity. The aim of this study was to identify the effect of a short-term diet high in sugar on susceptibility to colitis. Adult wild-type mice were placed on chow or a high sugar diet (50% sucrose) ± acetate. After two days of diet, mice were treated with dextran sodium sulfate (DSS) to induce colitis. Disease severity was assessed daily."

Spoiler

"The loss of intestinal barrier function in the mice fed the high sugar diet could have been due to either a direct effect of high levels of luminal sucrose or alternatively linked with a decrease in SCFA production. SCFA, including acetate, propionate, and butyrate, are produced by gut microbial fermentation along the entire intestinal tract including the small intestine[38,39]. SCFA regulate gut immune and barrier function, as well as having a role in epithelial cell proliferation, differentiation, and apoptosis. SCFA also promote nutrient absorption, lipid metabolism, mucin production, and expression of antimicrobial peptides[31]. The importance of acetate in gut health was reinforced by the improvement in colitis susceptibility following the supplementation of acetate. Acetate did not elicit any significant changes in bacterial community composition or increase levels of butyrate but was able to independently enhance the ability of high sugar fed mice to recover from an intestinal chemical insult. Several studies have previously shown that luminal acetate induces protective barrier effects in the intestine both directly through effects on epithelial cells and indirectly through effects on immune cells[40–42]. In addition, oral acetate has previously been shown to reduce severity of DSS colitis when given prior to DSS[43,44]. In our study, the loss of small intestinal barrier function that occurred during high sugar feeding was prevented by the provision of acetate in the drinking water."

"In conclusion, this paper provides mechanistic insight into the epidemiologic findings implicating a high-sugar diet in the triggering and perpetuation of inflammation in patients with inflammatory bowel disease. The results show that a short-term diet high in sugar results in an enhanced intestinal permeability coupled with a more inflammatory monocyte phenotype that results in an increased susceptibility to colonic insults and a lack of ability to repair damage. The findings that acetate alone substantially alleviates the deleterious effects of a high-sugar diet adds to the body of evidence suggesting that SCFAs play a crucial role in the response of the gut to insults and tissue repair."​

 

[Amazoniac]

- The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity

Spoiler: Summary

Spoiler: Chosen parts

"In general, saccharolytic fermentation mostly occurs in the distal ileum and proximal colon. The most abundant SCFA are acetate, propionate, and butyrate with an approximate molar ratio of 60:20:20, respectively [18–20]." "After colonic absorption and transition to the systemic circulation, the molar ratio changes to approximately 91:5:4, respectively, which are numbers that are based on findings in sudden death victims [22]."

Steroidogenesis | Colorado State University​

"Oral ingestion of vinegar rapidly increases circulating acetate as observed in healthy participants that increased serum acetate levels from 120 μmol/L during placebo conditions up to 350 μmol/L (after 15 min) and 200 μmol/L (after 30 min) after vinegar (100 mL containing 0.75 g acetic acid) and acetic acid capsules (containing 0.75 g of acetic acid) intake, respectively [47]. Acetic acid is a bioactive component with a dominant flavor in different types of vinegars including cider, malt, plum, sherry, tomato, and wine vinegar [48]."

"In addition, vinegars may contain other polyphenol residual components (e.g., gallic acid, catechin) such as in apple cider, grape, sherry, and Balsamic vinegar [48]. Therefore, it is important to consider the vinegar type since their composition of phenolic, flavonoid, and acetic acid content may differ [49]. In general, various dietary products such as preservatives, acidity regulators, food substitutes, ethanol, and vinegar may provide acetate orally. In particular, vinegar may provide rapid increments in plasma acetate levels due to its fast absorption in the upper digestive tract []. However, future vinegar supplementations should specify detailed composition including acetic acid percentage and polyphenols content."

"Microbial-derived acetate production is yielded by the fermentation of indigestible foods especially foods of acetogenic fibers (e.g., galacto-ligosaccharides, inulin) [50]. In postprandial conditions, acetogenic fibers can be fermented and may elevate production of acetate in the proximal colon [] [51]. When acetogenic fibers reach the colon, acetate is mainly generated by the microbial community via two metabolic pathways: acetogenesis and the carbon fixation pathway [52]. Acetogenesis is the production of acetate, mediated by homoacetogenic bacteria or acetogens (found in the digestive tract of humans and ruminants), which are capable to produce acetate from H2 and carbon dioxide (CO2) [53]. The carbon fixation pathway (also known as Wood-Ljungdahl pathway) produces acetate from CO2 as a precursor [52]."

"Acetogenic fiber characteristics (e.g., length, glycosidic bond configuration) may determine acetate production."

"In a Western diet (low fiber intake), protein fermentation occurs mainly in the distal colon where saccharolytic substrates are depleted [58] and this produces other compounds of toxic nature such as ammonia, amines, phenols, and sulfides [59]. Branched chain and aromatic amino acids may be produced and further metabolized via cross-feeding mechanisms and alter gut integrity and impair insulin sensitivity [60]." "[..]gut-derived acetate production is determined by the balance between saccharolytic and proteolytic fermentation and is especially determined by the presence of acetogenic fibers."

"Although gut-derived acetate production is expected to be low during states of low presence of fibers such as fasting, some studies suggest a possible contribution of fasting-induced alterations in the gut microbiota to fasting acetate concentrations [61]. This was accompanied by an increase in the Firmicutes/Bacteroidetes ratio and cross-feeding mechanisms as shown by an upregulation of pyruvate fermentation pathways to acetate and lactate by Lactobacillus reuteri and other unclassified bacteria [61]. In support, human fasting and caloric restriction interventions have described an increase in microbial diversity and abundance of important acetate producers, such as Akkermansia Muciniphila (A. muciniphila) and Bifidobacteria [62,63]."

"Acetate concentrations in the colon start with the highest levels in the caecum (69 mmol/L) and ascending colon (63 mmol/L), which was followed by a subsequent decrease in the transverse colon (57.9 mmol/L), descending colon (43.5 mmol/L), and sigmoid colon (50.1 mmol) (measured by kilograms of intestinal luminal contents) as observed in sudden death victims [22]. This progressive decline along the colon suggests that major acetate production and absorption occurs in the proximal colon. In general, microbially produced acetate in the proximal colon may follow a colonic-hepatic-periphery distribution starting with colonic levels in the mmol/L range, which was followed by a significant drop, around 10-fold in the liver, and reaching the periphery in the μmol/L range (See Table 1) [22]."

Spoiler

"[..]acetate production and colonic acetate release may vary along the colon. Thus, the site of fermentation and acetate production may be an important determinant of circulating concentrations."

"Appetite regulation is coordinated by nutrients and microbial metabolites through the central nervous system circuitry and circulating hormones from peripheral tissues [93]. Acetate has been reported to cross the blood-brain barrier in both mice [89] and humans [94]. Additionally, acetate has been detected in the cerebrospinal fluid, which suggests a central homeostatic mechanistic role [95]."

"Infusions in humans in different sites may elicit differential effects on gut-derived satiety hormones. For example, rectal (60 mmol/L) sodium acetate administrations increased PYY and GLP-1 significantly as compared to intravenous infusions (acetate 20 mmol/L and saline) [112]. Similarly, distal (not proximal) colonic infusions of sodium acetate (180 mmol/L) increased PYY in overweight/obese men and only 180 mmol/L (not 100 mmol/L) elicited these effects [39]. Moreover, rectal/intravenous infusions showed the potential to induce gut-derived hormone secretion (GLP-1 and PYY) in a metabolically disturbed phenotype [113]. Together, these distal colonic infusions studies suggest the relevance of the site of administration or fermentation (distal versus proximal colon) to modulate gut hormone secretion. Of note, a higher density of PYY producing cells in the distal colon in rodent studies [114,115] may explain the differential effect on hormonal secretion dependent on the site of fermentation."

"[..]a study in healthy and T2DM subjects, acetate intravenous infusions (2.5 mmol per minute for 1 h) did not increase energy expenditure, which was partly explained by the fact that acetate might replace long chain fatty acids as preferred oxidation fuel [121]."

"Studies related to vinegar effects on body weight and energy expenditure in humans are limited. Nevertheless, a few studies have reported effects on body weight. For instance, a study in individuals with obesity, a 12-week vinegar intervention significantly lowered body weight with low (0.75 g) and high (1.5 g) acetate doses versus placebo (0 g) in a dose-dependent manner [122]."

"With respect to differences in acetate infusions (sodium acetate) versus vinegar (acetic acid) administrations, both the route and absorption may differ. Saunders et al. [127] reported that oral acetic acid administration was more rapidly absorbed in the stomach when compared with sodium acetate administrations, possibly through a pH-dependent mechanism, since acetic acid (unionized acetate) absorption increased when gastric pH decreased."

"Human acute acetate infusions have shown inhibitory roles in whole-body lipolysis, increase in gut-hormone release, and increase in fat oxidation and energy expenditure among other effects (See Table 2). Collectively, these effects may improve adipose tissue lipid buffering capacity, satiety regulation, oxidative capacity, and, in turn, improve whole-body insulin sensitivity and peripheral tissue functioning. In addition, vinegar administrations have reported improvements in glucose homeostasis and insulinemic profiles. Moreover, we discuss vinegar effects on glucose homeostasis and insulinemic profiles with potential T2DM treatment applications [46]."

Spoiler

"[..]oral vinegar (4%–8% acetic acid) administrations may rapidly increase circulating acetate and its co-ingestion with carbohydrates (50–75 g), which seems more effective for glucose lowering and insulinemic responses. In contrast to colonic sodium acetate infusions, oral vinegar administrations have shown improvements in glucose homeostasis and insulin profiles in healthy subjects [46,130,131]. For instance, supplementation of acetic acid (unspecified vinegar) in healthy subjects together with a test meal resulted in reduced postprandial glucose concentration (~35%, during 30–70 min), putatively, through a delayed gastric emptying [130]. Similarly, white vinegar (6% acetic acid) administrations (18, 23, and 28 mmol/L) in combination with white wheat bread (50 g) in healthy subjects lowered glycemic (highest dose at 30–45 min) and insulinemic (highest dose at 15–30 min) postprandial responses [132]. In addition, acetic acid lowered the glycemic index (GI) and increased the satiety score postprandially at 30, 90, and 120 min using a subjective rating scale [132]. Another study in healthy subjects reported that a vinaigrette (28 g white vinegar, 6% acetic acid) on a potato meal reduced GI and insulinemic index (43 and 31%, respectively) [133]."

Spoiler

"In the human in vivo situation, a handful of studies demonstrated effects on lipolysis on the whole-body level. First, Crouse et al. [142] showed that orally administered sodium acetate (given in two doses 143 mg/kg initially and 71 mg/kg 30 min later) increased plasma acetate by three-fold to four-fold and decreased FFA plasma concentrations by 25% in healthy humans within 20 min after ingestion. Second, in healthy young subjects, an intragastric infusion of sodium acetate (12 mmol/L) significantly decreased the total AUC of circulating FFA in comparison to saline infusions during five hours after infusion [119]. Third, rectal infusion of high dose sodium acetate (180 mmol/L) decreased serum FFA in comparison to saline infusions in healthy subjects for 2 h after infusion [118]. Fourth, one-hour intravenous infusion of sodium acetate in healthy individuals increased plasma acetate from 0.19 to 0.99 mmol/L and inhibited whole-body lipolysis, as shown by the decrease in plasma glycerol and FFA concentrations [143]. Thus, both animal and human data show an antilipolytic effect of acetate that may decrease lipid overflow to peripheral insulin-sensitive tissues (e.g., skeletal muscle), which may possibly improve insulin sensitivity and decrease hypothalamic inflammation."

"Acetate may affect the proliferation and differentiation of adipocytes, which contributes to adipose tissue morphology, browning, and function. This can induce high thermogenic activity with the potential to enhance oxidative capacity [141]."

"Recently, intermittent fasting treated mice (every other day fasting, EODF) significantly induced the expression of browning markers (UCP1) in subcutaneous inguinal WAT, which was proposed to occur through gut-derived acetate since browning depended on gut microbiota depletion and transplantation [61]. In support, both colonic and serum acetate levels were significantly increased after both short-term and long-term intermittent fasting (3 and 15 cycles of 24 h, respectively), which suggests an acetate-mediated browning effect [61]."

"Under different pathological conditions, a leaky gut may occur and result in metabolic endotoxemia, characterized by high circulating lipopolysaccharide (LPS) levels, which can potentially lead to chronic low-grade inflammation. This is often observed in obesity and insulin resistance [152]. Gut-derived acetate may affect gut health via an improvement in intestinal barrier function through cross-feeding mechanisms (e.g., increased butyrate concentration) [153]. In an in vitro study, acetate (30 mmol/L) decreased LPS-stimulated secretion of the tumor necrosis factor (TNF-α) from human neutrophils by ~33% (p < 0.01) [154]."

"Intracellularly, acetate may be rapidly assimilated and metabolized through the TCA cycle in the mitochondrial matrix [162], contribute to the Acetyl-coA pool [163], and/or modulate signaling mechanisms involved in muscle lipid oxidation."

"Oxygen consumption rate measurements (using metabolic cage) reported 7% higher rates in acetate-treated rats, which indicates a possible increase in the whole-body metabolic rate following intragastric acetate infusion."

"[..]acetate may modulate skeletal muscle lipid and glucose metabolism possibly through activation (phosphorylation) of AMPK. Whether this affects endogenous intramuscular triglycerides (IMTG) and/or exogenous (dietary) lipid oxidation and glucose homeostasis in human muscle remains unclear."

"[..]the liver plays a central role in acetate metabolism, since important endogenous production occur here." "[It] occurs in all tissues but predominantly in the liver." "Furthermore, acetate may be rapidly metabolized and used as a carbon donor for intracellular pathways including cholesterol biosynthesis, acetylation processes [165], and hepatic palmitate formation [92]. Importantly, the liver is the first organ in direct contact with microbially-produced acetate coming from the ileum and proximal colon."

"The acetate: propionate ratio may be of importance for hepatic lipid biosynthesis since propionate may favor odd chain fatty acids while acetate may favor palmitate formation [169]. Moreover, odd chain fatty acids have been linked to improvements in insulin sensitivity [170]. Moreover, in men, it has been suggested that propionate may reduce acetate utilization for liver lipid biosynthesis (fatty acid and cholesterol) [171]. However, acetate has shown antilipolytic effects at the whole-body and adipose tissue level and increases in whole-body fat oxidation []. For instance, a 3-hour intragastric infusion of acetate (equivalent to the fermentation of 30 g of dietary fibers) in healthy subjects decreased plasma FFA, which possibly improved lipid profiles [119]. Importantly, SCFA reach the liver in different ratios. Therefore, single SCFA may not reflect physiological effects in the lipid profile. In general, in vitro and animal studies have provided mechanistic insight into the role of acetate in the liver, where it may increase the AMP/ATP ratio, and subsequently increase AMPK phosphorylation/activity and, thereby, affect hepatic lipid (FA oxidation) and glucose (glycogen) metabolism."

"Overall, both human acetate colonic infusions and vinegar administrations have reported effects to improve insulin sensitivity and glucose homeostasis. From a mechanistic perspective, acetate may modulate improvements in adipose tissue functioning, as well as through an increase in oxidative capacity (e.g., muscle, liver) and modulation of GSIS in the pancreas. Collectively, these tissue-specific effects may synergistically decrease lipid ectopic deposition and contribute to body weight control and glucose homeostasis."

 

[Astolfo]

In summary, is it toxic? How much benefit does it offer? Which one is preferable in terms of "alkalization" of the body, OJ + BS or ACV + BS?

 

[Amazoniac]

- Acetate Metabolism and the Inhibition of Bacterial Growth by Acetate

During aerobic growth on glucose, Escherichia coli excretes acetate, a mechanism called “overflow metabolism.” At high concentrations, the secreted acetate inhibits growth. Several mechanisms have been proposed for explaining this phenomenon, but a thorough analysis is hampered by the diversity of experimental conditions and strains used in these studies. Here, we describe the construction of a set of isogenic strains that remove different parts of the metabolic network involved in acetate metabolism. Analysis of these strains reveals that (i) high concentrations of acetate in the medium inhibit growth without significantly perturbing central metabolism; (ii) growth inhibition persists even when acetate assimilation is completely blocked; and (iii) regulatory interactions mediated by acetyl-phosphate play a small but significant role in growth inhibition by acetate. The major contribution to growth inhibition by acetate may originate in systemic effects like the uncoupling effect of organic acids or the perturbation of the anion composition of the cell, as previously proposed. Our data suggest, however, that under the conditions considered here, the uncoupling effect plays only a limited role.

IMPORTANCE
High concentrations of organic acids such as acetate inhibit growth of Escherichia coli and other bacteria. This phenomenon is of interest for understanding bacterial physiology but is also of practical relevance. Growth inhibition by organic acids underlies food preservation and causes problems during high-density fermentation in biotechnology. What causes this phenomenon? Classical explanations invoke the uncoupling effect of acetate and the establishment of an anion imbalance. Here, we propose and investigate an alternative hypothesis: the perturbation of acetate metabolism due to the inflow of excess acetate. We find that this perturbation accounts for 20% of the growth-inhibitory effect through a modification of the acetyl phosphate concentration. Moreover, we argue that our observations are not expected based on uncoupling alone.

 

[Amazoniac]

- Abnormalities of Acetate Metabolism in Adrenal Insufficiency in Man

Human adrenal insufficiency has been found in the present studies to be associated with marked decrease in the incorporation of C14 from C14 acetate into plasma triglyceride fatty acids and cholesterol.

Acetate oxidation is increased in mild adrenal insufficiency, together with an apparent generalized increase in the oxidation of various substrates to carbon dioxide. More marked adrenal insufficiency is associated with striking changes in the pattern of acetate oxidation and impaired ability to oxidize an acetate load.

Maintenance doses of adrenal steroids appear to be required for normal disposal of acetate. Possible mechanisms by which these effects might occur are discussed.

 

[Amazoniac]

Below is one more experiment showing changes in faecal bacteria when vinegar and acetic acid were ingested. Both moved inflammatory markers on the right direction, but the reason to be posting is because there were differences between them (read the publication), we should from now on produce a distinction between acetate and vinegarate salts.

- Vinegar Treatment Prevents the Development of Murine Experimental Colitis via Inhibition of Inflammation and Apoptosis

This study investigated the preventive effects of vinegar and acetic acid (the active component of vinegar) on ulcerative colitis (UC) in mice. Vinegar (5% v/v) or acetic acid (0.3% w/v) treatment significantly reduced the disease activity index and histopathological scores, attenuated body weight loss, and shortened the colon length in a murine experimental colitis model induced by dextran sulfate sodium (DSS). Further mechanistic analysis showed that vinegar inhibited inflammation through suppressing Th1 and Th17 responses, the NLRP3 inflammasome, and MAPK signaling activation. Vinegar also inhibited endoplasmic reticulum (ER) stress-mediated apoptosis in the colitis mouse model. Surprisingly, pretreatment with vinegar for 28 days before DSS induction increased levels of the commensal lactic acid-producing or acetic acid-producing bacteria, including Lactobacillus, Bifidobacteria, and Enterococcus faecalis, whereas decreased Escherichia coli levels were found in the feces of mice. These results suggest that vinegar supplementation might provide a new dietary strategy for the prevention of UC.

Spoiler

"Shizhen Li stated in his book that vinegar can disperse blood stasis, cure jaundice, attenuate yellow perspiration, and treat inflammatory diseases.[4] Vinegar has been used extensively since the era of Hippocrates as an antifungal and antibacterial agent for the treatment of numerous infections and ailments, including persistent coughs, head lice, insect bites, warts, ear infections, and wounds.[5] Recently, studies have shown that acetic acid exhibits important physiological activities, including metabolism promotion, detoxification, liver function improvement,[6] and especially antihypertensive and antihyperglycemic effects. Moreover, kurozu (a Japanese black vinegar) has been shown to have an anticolitis activity.[7]"

"The organic acids in dietary vinegar include acetic acid, lactic acid, formic acid, citric acid, malic acid, tartaric acid, and acetic acid, and these acids account for 90% of all of the organic acids in vinegar.[21] In the past decade, continuous intake (on a daily basis) of a drink containing 15 mL vinegar (750 mg of acetic acid) was reported to improve lifestyle-related diseases, such as hypertension,[22] hyperlipidemia,[23] and obesity.[24] Furthermore, animal studies demonstrated that acetic acid was the active ingredient responsible for the effects.[25−27] Acetic acid is absorbed immediately in the upper digestive tract after vinegar intake, especially the stomach and jejunum, and then circulates as acetate to the whole body.[28] Acetate is adequately absorbed by the body, and serum acetate levels rise above background levels.[28]"

"Some of the proposed mechanisms by which commensal bacteria may exert beneficial effects are (1) the acetic acid and lactate produced by Lactobacillus and Bifidobacteria, which inhibit the growth of potentially pathogenic organisms (e.g., Escherichia coli); (2) the increased transit time by the net flow of water from the blood to the intestinal lumen, which influences the adherence of bacteria to the intestinal wall; and (3) the reduced production of noxious substances.[37,38]"

"In previous studies, some researchers used 3−4% (v/v) acetic acid to induce colitis by intracolonic instillation. This did not conflict with our research results that high concentrations acetic acid (3−4% v/v) induced colitis by intracolonic instillation and low concentrations of acetic acid (0.3% w/v) or vinegar (5% v/v; acetic acid in 5% vinegar would be the equivalent of 0.3% acetic acid) in drinking water prevented experimental colitis in our study. Oral vinegar is mainly absorbed in the stomach and intestine, but locally instilled high concentrations acetic acid are largely smoldered in blood flow, leading to hemorrhage and tissue necrosis."

@methylenewhite

 

[Amazoniac]

- Acetate and Butyrate Improve β-cell Metabolism and Mitochondrial Respiration under Oxidative Stress

"Pancreatic β-cells are very sensitive to oxidative stress-induced mitochondrial dysfunction due to a relatively weak enzymatic anti-oxidative defense mechanism along with an inefficient repair system for oxidative DNA damage [25,26]. This is a major cause of islet loss in the process toward both type 1 and type 2 diabetes. Many report the beneficial effects of SCFA on glucose metabolism [14,15], but most of these effects are attributed to the increasing insulin sensitivity of peripheral organs rather than directly impacting β-cells to keep producing insulin under stress."

"Recently, acetate and propionate have been reported to improve insulin secretion and to protect against apoptosis in β-cells damaged by the cytokines interferon gamma, tumor necrosis factor alpha, and interleukin 1 beta and the fatty acid sodium palmitate [16,29]."

"Here, with the usage of both human islets and the MIN6 mouse β-cell line, we proved the direct effect of SCFAs on islets and β-cells. In human islets, we show that acetate and butyrate at 1 mM supported cell metabolism and prevented cell death. In the presence of STZ, the impact of both SCFAs was even more pronounced. Several studies have demonstrated that STZ induces damage mainly by provoking ROS and NO production in islet cells [33,34]. Therefore, as a possible mechanism for the protective effects of SCFAs, we measured after exposure to SCFAs the ROS/NO levels, mitochondrial function, and expression of GPR receptors. Incubation with 1 mM of both SCFAs strongly attenuated STZ-induced overproduction of ROS and NO, which might be caused by multiple mechanisms, including the amelioration of mitochondrial damage by supporting mitochondrial metabolism as an energy source. These two SCFAs seem to be able to reduce this oxidative stress, leading to improved islet-cell survival via, as we show here, regulating essential genes involved in mitochondrial dynamics."

"The SCFAs effects were dose-dependent; acetate and butyrate at a concentration of 1 mM enhanced β-cell viability and showed slightly improved metabolism at 2 mM, but no protective effects were observed at 4 mM. The physiological concentrations of acetate and butyrate in the portal and peripheral circulation were also found to be approximately 1 mM [38,39]. The loss of protection at higher concentrations and observed enhanced apoptosis at 4 mM with both SCFAs might be caused by multiple mechanisms."

"Acetate had a different effect than butyrate. Acetate showed more efficacy in supporting energy metabolism and anti-oxidative effects than butyrate. This might be caused by adaptations of β-cells to lower concentrations of butyrate in the pancreatic circulation. Butyrate is present at relatively lower concentrations compared to acetate because of the preferential use of butyrate by colonic epithelial cells for energy production [44]. Although there are no studies accurately quantifying and reporting the physiological concentration of acetate and butyrate surrounding islets, it is likely that butyrate concentrations will be lower and that β-cells will already benefit from butyrate at a lower concentration than that of acetate. However, we noticed that butyrate showed stronger effects on inhibiting GPR41 and NO generation, which suggests that butyrate function in β-cells might rely on a signal-mediated process via the SCFA receptor GPR41. Butyrate is sensed by GPR41 and stimulates a cascade of the signal transduction pathway [45,46], resulting in faster and more efficient energy metabolism toward β-oxidation, and the suppressed synthesis of inducible nitric oxide synthase."​

 

[Amazoniac]

- Acetate metabolism and aging: An emerging connection
- Tracking acetate through a journey of living world: Evolution as alternative cellular fuel with potential for application in cancer therapeutics

- From Sugar To Acetate - The Origins Of Acetyl-Coa Dictate Its Use In Cells And In Mice

- Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans
- Intravenous acetate elicits a greater free fatty acid rebound in normal than hyperinsulinaemic humans

 

[GorillaHead]

So if alcohol converts to acetate is this why alcohol provides a warming affect due to the acetate itself?

what are ways we can increase acetate production ? I read a study that acetate lowers Free fatty acids significantly.

 

[Amazoniac]

- Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review

"In brief, a solution that increases the body’s strong ion difference (the concentration of strong cations minus strong anions) will increase serum pH [15]. After injection and cellular uptake, the two-carbon acetate anion forms acetyl CoA and enters the citric acid cycle; the final by-products, carbon dioxide and water, are in a rapid equilibrium with bicarbonate through the catalyst activity of carbonic anhydrase [16, 17]. Thus, the infusion of sodium acetate increases the strong ion difference by causing a net increase in cations, as the acetate anion is metabolized out of the system."

"Sodium bicarbonate infusion can be thought of in a similar manner, whereby the end result is added sodium cations, an increased strong ion difference, and, in turn, increased pH. Sodium bicarbonate metabolism, however, is dependent on the near instant catalyst action of the ubiquitous enzyme, carbonic anhydrase. In contrast, acetate has numerous and complex metabolic pathways; this may reflect adverse events associated with sodium acetate overload."

"Sodium acetate metabolism was thought to occur primarily in the liver, but that has been disproved by several studies [18, 19]. Schumann et al. measured metabolic products of labeled acetate to assess the citric acid cycle and gluconeogenesis in the human liver [19]. The results of this analysis were inconsistent with hepatic metabolism alone, and the authors conclude that acetate cannot be used as a marker for gluconeogenesis or citric acid cycle activity in the liver. Acetate metabolism occurring in skeletal muscle accounts for the observation that liver disease does not adversely affect the handling of infused sodium acetate [19, 20]."

"Studies regarding the disposition of sodium acetate were primarily derived from the nephrology literature of 30 to 40 years past, when the drug was most commonly used as a dialysate buffer. Of note, the sodium acetate load during dialysis is much larger than that during standard intravenous infusion, and adverse events reported with dialysis may not parallel sodium acetate infusions in medical toxicology. This is highlighted by Tolchin et al. who suggested that sodium acetate used during dialysis may saturate its metabolic pathways; in a single dialysis treatment using a 40-mM sodium acetate bath and lasting 4 h, approximately 90 % of the acetate load is converted to bicarbonate [21]. Under these conditions, the authors calculated a maximum metabolic threshold of 48 μM/min/kg body weight [21]. As the sodium acetate load exceeds this level, acetate levels increase without an equimolar rise in bicarbonate. This rate of infusion translates to approximately 200 mM per h for a 70-kg person."​

It's about 12 g of acetate/h.

A steady supply of ethanol keeps it evelated:
- Increased Blood Acetate: A New Laboratory Marker of Alcoholism and Heavy Drinking

- Alcohol-derived acetate modulates brain function
- Increased brain uptake and oxidation of acetate in heavy drinkers


Short-chain triglyceride:
- Triacetin - Wikipedia (there's also tributyrin and tripropionin)
- Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma
- Volume accessibility of acid sites in modified montmorillonite and triacetin selectivity in acetylation of glycerol

Spoiler

But considering the previous article, edemium (Na) salt might be advantageous. If acetate is metabolized to waste productide (CO2), it can be breathed out or converted to hydrogen carbonate (HCO3) while edemium is going to remain in excess outside cells, so if the goal is impact this compartment, other ligands won't be as good (it would only be uni-winning).


Is the ability of glycine (aminoacetic acid) to control dextrose metabolism (as pointed out by Jorge a while ago) related to that of acetic acid? A measuring spoon of collagen or vinegar would have 30% or 5% of their weight as each toxin.

- Glycine acetate (1:1) | C4H9NO4 | ChemSpider
- Glycine Virtually Eliminates Adverse GI Effects Of Aspirin​

If you believe that the benefit of vinegar is beyond its acetic acid, it makes sense to choose those that are less concentrated in it (4% instead of 6%) provided that there's nothing undesirable when fermentation stops earlier.

 

[Amazoniac]

Diagram of intestinal lumen ↔ epithelial cells ↔ blood:

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From:
- Potential Application of the Synchronization Modulation Technique on Clinical Aspects

- Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans

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"AC [Air Conditioner] is largely taken up by the liver but 30–50% of colonic AC does reach the peripheral circulation where it can be used as an energy source."

"Participants were studied in the morning after 10–14 h overnight fasts. On the test day, participants collected fasting breath samples. Participants then put ~5 cm of the end of a piece of Tygon flexible plastic tubing (Norton Performance Plastics, Akron, OH, USA; o.d., 5mm) into their rectum, infused 500 ml of doubly distilled water, and emptied their colon and collected the voided solution/faecal material (baseline sample) in the collection bag provided to them. Participants then waited 15 min to ensure that there was no further urge to void. During this time, an indwelling intravenous (IV) catheter was inserted into a superficial forearm vein and kept patent with normal saline and fasting blood samples were collected. The tubing was then replaced into the rectum and 300 ml of the test solution containing 27 mmol of sodium acetate (Sigma Chemical, St Louis, MO, USA), was infused over a 10-min period."

That's about 1.6 g of acetate. A tablespoon of 6% acetate vinegar provides something like 0.8 g of it, so, two of them.

Normo- and Hyperinsulinemic.
​

It's expected for the level of this toxin to be lower after a while without food, but some of their victims had it below what's typical.

The point is the sharp rise after dosing.

If for whatever reason there's not enough acetate from the intestinal lumen, it may be possible for the epithelial cells to obtain it from the blood.

- Increased Blood Acetate: A New Laboratory Marker of Alcoholism and Heavy Drinking

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[Hgreen56]

Anyway I decided to give it a try. So I mixed 1 tsp of baking soda with white vinegar until it stopped forming the "volcano reaction". You have to divide this concoction in 3-4 doses. I divided it in 3 doses and drank the first one. Half an hour later I experienced what seemed like a metaboolic boost. Heat all over my body and energy. What's more important : I felt a very STRONG reducing in anxiety/adrenalin. At first I though... WOW! Maybe I have SIBO and this is killing the ******* bacteria that is eating up my GABA, creating LPS and stuff... Then I though... Hold on a second... maybe it's just plain old sodium calming the stress reaction like we all know. Ray says it. Salt diminishes adrenalin.

isn't the low ph and acetic acid in vinagar destroying the tooth enamel? how do you drink it?

 

[Makrosky]

isn't the low ph and acetic acid in vinagar destroying the tooth enamel? how do you drink it?

I didn't notice any enamel damage. I think enamel regrows anyway? Or am I mistaken?

I didn't drink it for long periods of time IIRC. Maybe a week at max. And it has to be diluted with water or juice or something because it tastes like HELL. So by that I think it can't destroy the enamel.

Are you using it?

 

[Hgreen56]

I didn't notice any enamel damage. I think enamel regrows anyway? Or am I mistaken?

I didn't drink it for long periods of time IIRC. Maybe a week at max. And it has to be diluted with water or juice or something because it tastes like HELL. So by that I think it can't destroy the enamel.

Are you using it?

i have tried it in the past.
the vinegar irritate my intestine like fruit juice's do that are very high acidic.
High acid is very bad for teeth.

 

[SaltiestSardine]

You lot must be using too much vinegar then..i didn't get any enamel erosion from this even when i was an extreme risk for dental caries about 2 years ago when something as simple as drinking orange juice would cause erosion for me. i've supplemented with Sodium Acetate on and off since reading about it. when my anxiety is really high, which makes digesting anything a real chore i often incorporate it as i find it pretty therapeutic(tried experimenting with his calcium acetate as well but i could never get it to react with white vinegar, or ACV)i find it really gives me a boost and it has some minor but noticeable effects on sexual function shortly after consuming(warmer and fuller flaccid penis) which is probably from CO²

 

[Amazoniac]

- Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest

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"The extent of histone hypoacetylation is linked to promoter CpG hypermethylation, silencing of tumor-suppressor genes, and poorer clinical outcomes (Seligson et al., 2009). Several histone deacetylase inhibitors (HDACi) (e.g., sodium butyrate, trichostatin A, Vorinostat) have shown promise in glioma treatment (Roesler et al., 2010). However, HDACi have serious limitations, including ineffective penetrance into solid tumors, cardiotoxicity, and thrombocytopenia (Duvic et al., 2007; Gryder et al., 2012). Safe alternative approaches to promote and/or maintain histone acetylation are required; yet, to date researchers have not investigated acetate supplementation as a therapeutic approach. Normally, most of the nuclear acetate required for histone acetylation is derived from glucose via ATP-citrate lyase (ACL)-mediated conversion of mitochondrial-derived citrate to acetyl-Coenzyme A (acetyl-CoA) (Fig. 1) (Wellen et al., 2009). However, in highly proliferative, glycolytic tumor cells, citrate is exported from the mitochondria to the cytosol to support lipid synthesis and biomass accumulation (i.e., Warburg effect) (Hatzivassiliou et al., 2005; Koppenol et al., 2011). This suggests that an alternative nucleocytosolic acetyl-CoA synthetic pathway, distinct from ACL, may provide a therapeutic target."

"N-acetyl-L-aspartate (NAA) is the most concentrated source of acetate in the human brain (12.1 ± 1.5 mM) (Rigotti et al., 2011). Aspartoacylase (ASPA) catalyzes the breakdown of NAA, its only known substrate (Kaul et al., 1991), to L-aspartate, for use in protein synthesis and the Krebs cycle, and acetate (Fig. 1). Free acetate is then converted to acetyl-CoA via cytosolic/nuclear acetyl-CoA synthetase-1 (AceCS1) for lipid biosynthesis and histone/protein acetylation (Goldberg and Brunengraber, 1980) and via mitochondrial AceCS2 for ATP production (Fig. 1) (Fujino et al., 2001). Both NAA and ASPA protein levels are decreased in glioma (Moffett et al., 2007; Tsen et al., 2014). Thus, decreased NAA-derived acetate bioavailability could contribute to histone/protein hypoacetylation as well as an increased glycolytic state by further exhausting the mitochondrial citrate supply. NAA-mediated acetate supplementation is not a candidate therapeutic approach since NAA catalysis requires ASPA, which is also decreased in glioma. Furthermore, we recently demonstrated that NAA promotes GSC proliferation in vitro via mechanisms that remain to be determined (Long et al., 2013a). Hence, an alternative acetate source is required."

"Triacetin (glyceryl triacetate, GTA) is ideal for therapeutic acetate supplementation. Unlike free acetate, GTA is readily absorbed by the gastrointestinal tract, freely crosses the blood-brain barrier and plasma membranes, and is hydrolyzed by non-specific lipases and esterases in all cell types to liberate glycerol and acetate. Glycerol can either participate in de novo triglyceride synthesis or be used for glycolysis after conversion to glyceraldehyde-3-phosphate, while the acetate generates acetyl-CoA (Fig. 1) (Reisenauer et al., 2011). Thus, GTA serves as an ideal acetate delivery vehicle."

"We demonstrate that GTA induces cytostatic growth arrest of primary tumor-derived GSCs more than established human GBM cells (U87 and U251), but has less effect on normal cells (i.e., normal human astrocytes and murine neural stem cells [NSCs]). Interestingly, GTA is more effective at growth arrest than sodium acetate and glycerol comparable to that generated by complete GTA catalysis. GTA-mediated acetate supplementation does not induce anti-proliferative effects via the promotion of differentiation or apoptosis, but increased acetylation of several proteins, suggesting an epigenetic mechanism of action."