Has Anyone Tried Sodium Acetate ? (for SIBO?)

I don't know why, but when you combine sodium bicarbonate with selenomethionine, then add vinegar, it fizzes in a different way; the reaction is more intense than sodium bicarbonate alone and the bad odor diminishes. Maybe selenomethionid becomes less prone to putrefaction this way. On the hands of the others, it might change something that makes it more difficult to be digested.

 

I just started doing ACV and BS a couple times a day and I am liking the effects. Too early to tell what the results will be but I can see that it may have an effect on water weight around the middle.

 

Positive or negative?

I've been using it too. Its great. I got a friend with serious asthma using it too and he immediately went off medication and inhaler and is doing great.

 

I never considered trying bull**** before.

 

I've always spelled out "baking soda" for that reason. But you ought to try BS. Works sometimes.

 

Haha yes baking soda. I used to use ACV quite a bit as I was a big fan of folk remedies but seriously I abandoned so many good things when I realized I could subsist on sugary food all day . I also have felt the metabolism boosting effect. Digestion feels cleaner, although I also started at the same time increasing my fiber so I can maybe increase my elimination, I know I was very against it, but..... I am open minded to trying new things when old things are not working so well.

 

I am considering trying this for CFS as pyruvate oxidation , which is one way of creating acetylcoa, is diminished. On one hand, just straight up vinegar should help, as it gets converted into acetate in vivo, but I guess the sodium acetate, b/c basic, could be easier on the stomach?

There's not a ton of safety data on it in humans but nevertheless it seems pretty safe

Also an interesting tidbit: it's used as a food additive, specifically for salt and vinegar potato chips. I've always like that taste!

 

One of the guys I helped couldn’t seem to get any improvement to his SIBO after 18 months of diarrheas and liquid stools, within A WEEK his digestion normalized.

- water or tea only, away from meals
- betaine HCL each meal
- MAXIMUM 10g of fats per meal (he has 4 a day bc he lifts)
- obviously basmati, whole fruit, potatoes as his preferred carbs. 60-65% ish of his macros

He ended up identifying right away which foods caused him troubles and ended up throwing away eggs, oatmeal, and now is on a quite restrictive diet trying to introduce one food at a time. Hit or miss. In the meantime his digestion is back to normal.

 

So I asked ray about this and he said "Its similarity to fat suggests that it could lead to under-production of CO2, leading to other problems"

And I thought "what??"

Then I looked for sodium acetate in his articles, he doesn't mention it directly but cites this in an article about salt: Effects of infused sodium acetate, sodium lactate, and sodium beta-hydroxybutyrate on energy expenditure and substrate oxidation rates in lean humans. - PubMed - NCBI

"Infusion of sodium acetate in lean humans results in a decrease in respiratory exchange ratio, which may be advantageous in patients with respiratory failure. However, this potential decrease in respiratory work was observed to be offset by significant thermogenesis. The metabolic effects of sodium acetate, sodium lactate, and sodium beta-hydroxybutyrate, infused at a rate of 20 mumol.kg-1.min-1 for 3 h, was monitored in six healthy human volunteers. Respiratory exchange ratio decreased from 0.85 +/- 0.02 at baseline to 0.75 +/- 0.02, 0.75 +/- 0.02, and 0.80 +/- 0.02, after acetate, lactate, or beta-hydroxybutyrate, respectively (P < 0.05 for each). Acetate produced a larger thermic effect (22.7% of energy infused) than did lactate (16.3%) or beta-hydroxybutyrate (13.6%). Thus, sodium salts of organic acids may potentially decrease the respiratory requirements by decreasing the respiratory exchange ratio. However, this effect is partially offset by the thermic effect of these substrates. The maximal doses and safety of these anions during larger infusion periods remain to be determined."

Okay, so thermogenesis, that's good, right? But apparently it decreases the C02/O2 ratio. Which also happens with ketosis or eating more fats.

Respiratory exchange ratio - Wikipedia

With only fats, the ratio would be about .7, whereas normally it's about .8. In this paper, it started at .85 and decreased to .75

But then this also says that in anaerobic exercise, the respiratory ratio raises a lot, to above 1. Well, that makes it sound like increased CO2 is stressful. But I would bet that it's also a compensatory mechanism for the stress of anaerobic metabolism, to increase oxygenation via the Bohr effect. So maybe we want a higher respiratory ratio?


But at the same time, thermogenesis--that seems good. As well as the fact that it would feed the kreb's cycle via providing an alternate source for acetylcoA, whereas people with CFS have problems with pyruvate oxidation. Hmm. It seems possibly worth a try. It seems like it could be similar to keto, maybe not ideal long term, but could provide temporary relief by providing an alternate fuel source for people who are having trouble with normal oxidative metabolism.

@Travis thoughts? Also, @SB4 I thought you might be interested in this.

@Travis my main question is, would you think that the thermogenesis and subjective beneficial effects would be due to the decrease in respiratory ratio specifically, e.g. could one take this and also take CO2 and not cancel out the effects?

 

Interesting.

I'll point out that you are talking IV sodium acetate. Did you ask him about oral ingestion?

 

That study is IV sodium acetate, but I just asked him about taking it as a supplement period. I assume he thought I meant oral, because how many people out there are gonna run sodium acetate IVs on themselves?

 

Interesting. I've mentioned to him using magnesium acetate (Mg carbonate reacted with apple cider vinegar) and he didn't say anything about it. I wonder if the issue is acid salts of sodium or acid salts in general.

 

i'

i'm pretty sure that study had magnesium acetate too but it yielded a diff. respiratory ratio/less dramatic effects? gotta look at it again

 

Thanks. Do you have the full text? I only see the abstract.

 

I see the thermogenesis as a direct consequence of metabolism, and cannot realistically imagine any way to produce heat besides. I feel the confusion had started with the very discoverer of the uncoupling protein, D.G. Nicholls, who had noted an increase of heat independent of cellular changes in adenosine nucleotides. This observation of course would imply no change in metabolic rate had occurred, leading Nicholls and others since to hypothesize a perpetual and rapid 'electron cycling' between either side of the mitochondrial membrane. However: Nicholls had not measured guanosine nucleotides, and it has been since demonstrated that uncoupling protein has a GDP-binding domain. What uncoupling protein actually appears to accomplish is to switch oxidative respiration from adenosine to guanosine nucleotides. This could be expected to increase metabolism on account of a greater GDP substrate availability because most mitochondrial surface area would still be converting ADP into ATP. So if something should increase body heat without effecting vascular tone—i.e. facilitating environmental heat exchange—I feel it could only be doing so by affecting the metabolic rate. But since acetate regenerates the citric acid cycle via acetyl–coenzyme A, you might expect that it would liberate just as much CO₂ as hexose metabolism. Yet once it's noted that pyruvate decarboxylase—together with thiamine and α-lipoic acid—is the enzyme responsible for synthesizing acetyl–coenzyme A during normal hexose metabolism, then acetate's effect on the respiratory exchange ratio can perhaps be understood by its annulment of the made-superfluous CO₂ liberated through the pyruvate pathway.

 

I tried pretty hard to parse this, but struggling.

So most things that increase uncoupling protein and increase thermogenesis, like caffeine, T3, etc--would increase CO2? As an aside, why is DNP, which is an uncoupler, so toxic, whereas these other chemicals are generally beneficial? Does it simply increase thermogenesis and uncoupling too much without some kind of rate limiting or compensatory mechanism?

For practical purposes, the last line, "annulment of the made-superfluous CO2"--does that imply that in this case the effects on metabolism make CO2 less necessary, and therefore it could still be beneficial?

Is it always good to keep the respiratory exchange ratio higher? It seems like carbon dioxide could be compensatory in some way, since it's increased in anaerobic exercise, so maybe if metabolism/thermogenesis are increased some other way, it's less necessary. But Ray seems to think that its tied overall to redox chemistry, etc., in a way that its good for metabolism and not having it is bad for metabolism, sort of binary oppositions, with diff. substances.

 

I certainly think uncoupling protein would increase oxygen flux, glycolytic rate, NADH formation, heat output, carbon dioxide production, and CO₂ flux—yet not necessarily its concentration. Carbonic anhydrase, which has multiple isoforms, can be expressed in many locations in diverse concentrations. Such things as γ-aminobutyric acid, methylglyoxal, and histamine have all been shown to influence the catalytic rate. Since methylglyoxal is formed from sugar metabolism and increases the enzyme's rate (Biswas, 2012), then concentration of carbon dioxide resulting from increased glycolysis could be partially-offset in some people more than others.

I believe this is because it is metabolized into primary amines—e.g. 5-amino-3-methylcatechol (Lenke, 1992)—all of which take a positive charge at physiological pH. Positively-charged ions and small molecules are attracted to the negative mitochondrial membrane potential (ψ ≈ −180 mV), and mitochondrial histology stains and assay reagents are always cationic by necessity. Ammonia (NH₃) largely becomes ammonium (NH₄⁺) at physiological pH, and I believe the toxicity from this derives from its displacement of intracellular potassium (K⁺) and mitochondrial affinity. Yet there could of course be a different means in which dinitrophenol 'uncouples' mitochondria besides a physical 'smothering effect,' and I have yet to read an article that had proposed a mechanism of action.

I suppose higher-than-average carbon dioxide could be better in many ways, and perhaps a better word than 'superfluous' would have been 'excessive.' I think perhaps I even had the word 'extraneous' in mind, yet had somewhat confounded that with 'superfluous' at some point. Besides that: I still think it's easy to see why acetate should produce less carbon dioxide than pyruvate, and also why Ray Peat was fair in likening acetate to fat metabolism. Beta-oxidation of course produces acetate without liberating any carbon dioxide in the process, yet glucose and fructose metabolism ultimately leads to pyruvate which releases CO₂ in forming coenzyme A-bound acetate. Taking acetate effectively bypasses pyruvate's carbon dioxide emitted when forming acetate. So sucrose should lead to a greater carbon dioxide flux than an isocaloric amount of fat.

That is fair, and some people could certainly do better with more carbon dioxide. I sleep with my head under my blankets so I do get a slightly hypercapnic at night, and thus far haven't experienced many side-effects. I had actually found an older article out of curiosity that had studied this, and the doctor–writer had concluded that the slight hypercapnia induced from this would be harmless. Yet with increased carbon dioxide flux comes more acidity, as carbonic acid is generated by carbonic anhydrase by using this as substrate.

 

Yes, and since problems with pyruvate dehydrogenase, or pyruvate oxidation have been demonstrated in CFS, this was originally why i was interested in this substance, sodium acetate, to "bypass" that step and make acetylcoa via a different route. But I would imagine ray would rather one use either something to activate PDH more, or directly impair PDK, like thiamine or DCA respectively. May have to revisit thiamine.

That said, would taking sodium acetate be as intense as keto? I have no desire to do a ketogenic diet, even though it "bypasses" this step that may be impaired in CFS patients, partially because ray considers it so stressful but also partially because it seems intuitively bad and anecdotes abound of it making people worse. But if I could induce this change in metabolism in a gentler way, like sodium acetate does, I might consider it beneficial.

 

I was trying to find out if it's common to have a reduction in acetic acid in the small intestine when there's bacterial overgrowth to justify its supplementation. Then, where is the main site for absorption of dietary short-chain fatty acids and if it coincides with regions that tend to be infected, or at least if it can have an affect that alters things downstream. Next, is it better to supply acetic acid or acetate? And finally, what if some pathogenic bacteria is actually feasting on it and this is the reason why it's low? It would not make sense to provide more.

I wasn't able to answer them all, but these are relevant:

- Small intestinal bacterial overgrowth syndrome

"SIBO may be accompanied by both maldigestion and malabsorption. Bacteria in SIBO might significantly interfere with enzymatic, absorptive and metabolic actions of a macro-organism. Due to injury of the brush-border of enterocytes, the activity of disaccharideses may be decreased. If bacteria simultaneously metabolise fructose, lactose and sorbitol, malabsorption of saccharides may occur. Injured small intestinal mucosa can have undesirable consequences in increased intestinal permeability and/or protein-losing enteropathy. Deficiency of vitamin B12 results from the consumption of this vitamin by anaerobic micro-organisms. Bacteria may also utilise intraluminal protein in the small bowel, this may lead to protein deficiency for the macro-organism and excessive production of ammonia by bacteria. Deconjugation of bile acids by bacteria results in malabsorption of fat and liposoluble vitamins. Extensively formed lithocholic acid is poorly absorbable and acts enterotoxically[5,7,93-95].

Bacteria produce various toxic agents that may have surprising systemic effects. These agents are ammonia, D-lactate, endogenous bacterial peptidoglycans and others. SIBO is regularly associated with increased serum endotoxin and bacterial compounds stimulating production of (pro)inflammatory cytokines[7,96]. SIBO might be associated with endogenous production of ethanol (probably synthesised by Candida albicans and Saccharomyces cerevisiae). Serum ethanol disappears after successful treatment of SIBO[37].

Small intestinal bacterial overgrowth has a negative impact not only on the function but also on the morphological structure of the small bowel. Microscopic inflammatory changes (especially in the lamina propria) and villous atrophy are found regularly. In such a case, the villous atrophy in SIBO must be distinguished from that of coeliac disease. Macroscopic changes may also be visible in some patients. Hoog et al[97] found small intestinal mucosal breaks (erosions or ulcers) in 16/18 patients with chronic myopathic or neuropathic motility disorders of the small bowel by means of wireless capsule endoscopy."

"SIBO may be clinically asymptomatic or can resemble irritable bowel syndrome with non-specific symptoms (bloating, flatulence, abdominal discomfort, diarrhoea, abdominal pain). In more severe cases, there are signs of malabsorption (weight loss, steatorrhoea, malnutrition), liver lesion, skin manifestation (rosacea), arthralgias and deficiency syndromes (anaemia, tetany in hypocalcaemia induced by vitamin D deficiency, metabolic bone disease, polyneuropathy due to vitamin B12 deficiency, impaired barrier function of the gut, etc.). Anaemia is usually macrocytic (megaloblastic) due to vitamin B12 deficiency. It could also be microcytic iron deficiency (due to occult gastrointestinal blood loss) or normocytic (as anaemia of chronic disease)[3,5-7]. Serum folate and vitamin K levels are usually normal. Serum vitamin K can even be increased owing to its bacterial overproduction. Moreover, there are some concerns as to whether endogenous intestinal production of vitamin K by bacteria might interfere with warfarin treatment in SIBO[98-100]. In the case of oedema of lower extremities, the aetiology is usually more complex (anaemia, malnutrition, hypoproteinaemia, vitamin B12 deficiency)."

"D-lactic acidosis is a severe complication of patients with short bowel syndrome (with intact large bowel). It is caused by an excessive overgrowth of lactobacilli. Non-absorbed saccharides pass from the small intestine to the large bowel and they are fermented down to the D-isomer of lactic acid. There is no human pathway to metabolise D-lactic acid. D-lactic acid is absorbed from the large bowel; its serum concentration is regularly increased in these patients. Nevertheless, most patients remain asymptomatic. In clinically expressed cases, leading symptoms comprise characteristic neurologic abnormalities including confusion, cerebellar ataxia, slurred speech, and loss of memory. Patients exhibit some degree of altered mental status. They may complain of or appear to be drunk in the absence of ethanol intake. In the treatment, it is necessary to compensate metabolic acidosis and administer peroral antibiotics (metronidazole, rifaximin). To prevent this serious complication, it is important to reduce peroral intake of simple sugars, polysaccharides given in smaller amounts together with a higher intake of fat[101]."

"Therapy for SIBO must be complex (addressing all causes, symptoms and complications) and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics.

The most important thing is always treatment of the basic underlying disease if possible. Nutritional support is mandatory in SIBO associated with malnutrition, weight loss and nutrient deficiency."​

- Regulation of short-chain fatty acid production

"The principal SCFA that result from both carbohydrate and amino acid fermentation are acetate, propionate and butyrate, although formate, valerate, caproate and the branched-chain fatty acids isobutyrate, 2-methyl-butyrate and isovalerate, which are formed during the catabolism of branched-chain amino acids (valine, leucine, isoleucine), are also produced in lesser amounts (Macfarlane & Macfarlane, 1995). Other fermentation products such as lactate, ethanol and succinate, which are intermediates in the global fermentation process in the microbiota, are to varying extents metabolised to SCFA by cross-feeding species in the ecosystem, and they do not usually accumulate to a substantial extent in the bowel (Bernalier et al. 1999)."

"As a result of depletion of C sources in the proximal large intestine, particularly readily-digestible carbohydrates, a progressive reduction in bacterial substrate availability occurs as food residues move towards the distal gut. This situation affects the types and amounts of SCFA produced, as does the length of time digestive material spends in the colon (Cummings, 1978; Cummings et al. 1979, 1992). In vivo and in vitro studies show that long transit times in the large intestine can have profound effects on bacterial physiology and metabolism, leading to protein breakdown and amino acid fermentation making an increased contribution to colon SCFA pools (Macfarlane et al. 1992, 1994, 1998)."

"In addition to the importance of gut transit time, mentioned earlier, many host-related factors affect bacterial metabolism and SCFA formation in the gut, including diet and other less direct determinants such as ageing, neuroendocrine system activity, stress, pancreatic and other secretions in the digestive tract, mucus production, disease, drugs, antibiotics and epithelial cell turnover times. From a microbiological viewpoint, the chemical composition, physical form and amount of substrate available affects bacterial fermentation reactions, which are also dependent on the types and numbers of different bacterial populations in the gut, catabolite regulatory mechanisms, the availability of inorganic electron donors, such as nitrate (Allison & Macfarlane, 1988) and sulfate (Gibson et al. 1993), as well as competitive and cooperative interactions between different species in the microbiota (Macfarlane & Gibson, 1994)."

"Nitrate and sulfate have been shown to profoundly affect fermentation reactions during carbohydrate breakdown under anaerobic conditions. This effect is typically manifested in the form of increased acetate production, together with reduced butyrate and lactate formation (Allison & Macfarlane, 1988; Gibson et al. 1993). This process occurs because these inorganic anions act as electron sinks, which enables some intestinal bacteria to use hydrogen as an electron donor in metabolism."

​

- Short-Chain Fatty Acids in the Small-Bowel Bacterial Overgrowth Syndrome

"Bacterial overgrowth of the small intestine occurs mainly in patients with reduced gastric acidity or increased retention time in the whole or parts of the small bowel (1,2). These conditions are followed by quantitative and qualitative changes in the bacterial flora in the small intestine (2-4). If this flora causes clinically significant disturbances of gut functions, the condition is termed small-bowel bacterial overgrowth syndrome (BO) (5)."

"The median total concentration of SCFAs in jejunal secretions from patients with bacterial overgrowth was 990 pmol/l (range, 210- 12,370 vmol/l) (Table 11). Acetic acid accounted for an average of 61.0%, propionic acid for 15.6%, and n-butyric acid for 8.3%, respectively, of the total concentration. Isobutyric, isovaleric, and n-valeric acid were also present in low concentrations."

"The total concentration of SCFAs was about four times higher in jejunal aspirates from patients with bacterial overgrowth than in control patients (p < 0.01) and healthy subjects (p < 0.025) (Table 111). The relative distribution of the acids was different, with significantly less acetic acid and more isobutyric, n-butyric, isovaleric, and n-valeric acid in jejunal aspirates from BO patients than the other two groups (p < 0.025 for each of these acids)."

"The relative distribution of the acids resembled the fecal pattern more than the oral pattern, supporting the view that a colon-like flora is present in the small bowel of these patients (4)."
And this is why the diagram above was included.

"Treatment with peroral antimicrobial drugs for a few days may lead to normalization of the concentrations and distributions of SCFAs in the jejunal secretions of patients with BO, supporting the view that these acids are of bacterial origin (7)."

"As might be expected, large individual variations in the concentrations and patterns of SCFAs were observed in the patients with bacterial overgrowth. The concentrations of SCFAs probably depend on various factors such as localization and type of pathological lesion in the small bowel, retention time and flux of fluid in the diseased segment, composition of the abnormal flora, and substrate available for fermentation. To which extent the jejunal fluid is sampled at a close vicinity to the most affected part of the small bowel may be of great importance. In the present study all aspirations were made from a position approximately at the ligament of Treitz. It is possible, therefore, that we would have found higher concentrations and more abnormal patterns if we had aspirated from the sites of the lesions in all patients. This may be illustrated by patient B08, who had bacterial overgrowth by our definition but had normal concentrations and pattern of SCFAs. Later examinations showed that she had stenosis at the ileocecal junction, with extensive dilatation of the ileum but a normal jejunum."

"Analyses of SCFAs in jejunal secretions may prove to be valuable in the diagnosis of bacterial overgrowth in clinical practice. However, one subject in each of the control groups had elevated concentrations and/or an abnormal distribution of the acids. Thus, a combination of diagnostic tests (e.g. cultivation of jejunal secretions, H2 breath test, and analysis of jejunal SCFAs) must be used to ascertain the diagnosis."​

 

- Bifidobacteria can protect from enteropathogenic infection through production of acetate
- Starch and starch hydrolysates are favorable carbon sources for Bifidobacteria in the human gut
- Xylooligosaccharide increases bifidobacteria but not lactobacilli in human gut microbiota*
- A review on xylooligosaccharides*
*Not encouraging the use of these, it's just to think about what's in them that can favor the growth of beneficial bacteria that can provide the missing acetate.

But one of the reasons for questioning its use is that it can also feed problematic bacteria (most are found in the colon, but some of them have been detected in the small intestine as well).
- Methanogenic archaea and sulfate reducing bacteria co-cultured on acetate: teamwork or coexistence?