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Baking Soda Dramatically Increases Antibiotic Effectiveness, Could Help In Sepsis

haidut

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Recently we posted some studies showing that thiamine (by itself or vitamin C) dramatically increases survival in sepsis, and lowers its severity.
IV B1+Vit. C+ Cortisone Prevents Septic Induced Death

Sepsis is the number one killer of hospitalized patients, so finding a way to reduce its lethality is perhaps one of the most important goals of clinical medicine.
This new study below shows that baking soda, in physiological concentrations, not enhances the effects of antibiotics (thus reducing needed dose) but also somehow interferes with the bacteria's ability to produce energy (which makes them even more vulnerable to antibiotics). Notably, the effects of baking soda were NOT related to pH change, as that was purposefully kept stable. In addition, baking soda was found to be innately antibacterial, even without the presence of antibiotics. Furthermore, it was the bicarbonate ion that was responsible for all of these effects, not sodium or other metal salts tested.
I wonder if the effects of thiamine in sepsis are not due to a similar mechanism or the inhibition of carbonic anhydrase, which has effects on bicarbonate levels. I suspect combining bicarbonate and thiamine would be even more effective. So, maybe orange juice with baking soda and some thiamine could become a good home remedy for (subclinical) endotoxin overload.
@Travis @Koveras @aguilaroja @Such_Saturation

http://pubs.acs.org/doi/10.1021/acsinfecdis.7b00194
"...We first analyzed the interaction of sodium bicarbonate (pH 7.4) with conventional antibiotics at the sub-minimum inhibitory concentration (MIC) but physiological concentration of 25 mM. Our goal was to establish the nature of the interaction with various chemical classes of antibiotics as a first step to understanding the mechanism of action of bicarbonate. Remarkably, eight classes of antibiotics investigated had appreciably altered activities in the presence of a physiological concentration sodium bicarbonate. The fold enhancement in MIC for a variety of antibiotics in standard microbiological media relative to media supplemented with sodium bicarbonate is shown for E. coli and S. aureus in Figure 1 and Table S1. With a few exceptions, these Gram-negative and Gram-positive bacteria, behaved similarly."

"...Importantly, the chemical bicarbonate was uniquely responsible for the enhancements observed. The activity was not due to a trivial effect on pH. Test media were pH-adjusted upon addition of sodium bicarbonate for all studies reported herein. Of note, sodium bicarbonate at physiological concentration (25 mM) produces media with a pH typical of standard susceptibility testing conditions. Further, using dirithromycin as a test case, we tested many equimolar organic salts, with differing ionic strengths and steric properties, and none had impact on antibacterial activity, ruling out osmotic-mediated mechanisms (Table 1). Lastly, sodium did not contribute to the potentiation of dirithromycin, as equally potent synergy was observed with other salts of bicarbonate (Table 1)."

"...Nevertheless, our experiments suggest that in the bicarbonate-rich environment of the host, energy-dependent efflux systems may be less effective than predicted by increases in MICs in conventional in vitro MIC determinations, often assumed to be the result of efflux pumps. Interestingly, macrolide antibiotics have been previously shown to be potentiated by normal human serum, but the serum factor responsible for the effect has remained elusive25. Our studies suggest bicarbonate is the causative agent."

"...Accordingly, we observed a profound effect on cellular respiration (70% reduction) in E. coli treated with 25 mM sodium bicarbonate (Figure S5A). Consistent with this finding, E. coli grown in high concentrations of sodium bicarbonate exhibited an extended lag phase, implying lowered metabolic resources (Figure S5B). Further, intracellular ATP levels, which are produced via the F0F1-ATPase utilizing PMF, were reduced by ~30% in sodium bicarbonate-treated E. coli compared to the untreated control (Figure S5C). Overall, these experiments suggest that bicarbonate is a bacteriostatic compound that perturbs cellular respiration and reduces the activity of cell wall-active antibiotics that require actively growing bacteria for activity. Chemical genomics studies further reveal action of bicarbonate on the proton motive force."

"...Finally, decreased promoter activity was also observed for many ATP-dependent processes, likely as an adaptive effort to conserve energy. Overall, E. coli adaptation to bicarbonate involved strategies to respond to periplasmic pH changes, increase membrane potential and preserve energy. Bicarbonate selectively dissipates the transmembrane pH gradient."

"...To this end, we investigated the influence of sodium bicarbonate (pH 7.4) on the in vitro antibacterial activity of various secretory molecules and cellular components that make up innate immunity against bacterial pathogens. Sodium bicarbonate itself exhibited antibacterial activity against many clinically relevant pathogens, with MIC values ranging from 50-100 mM (Table S4). We assessed the ability of sodium bicarbonate, at the sub-MIC but physiological concentration of 25 mM, to potentiate the activity of various mediators of host defense, including defensins and cathelicidins, whose family members make up the principal components of innate immunity in vertebrates36. The antimicrobial activity of alpha-defensin and LL-37 were enhanced 4 to 8-fold against E. coli (Figure 4A,E) and S. aureus (Table S5). Other antimicrobial peptides, such as indolicidin and bactenesin, were also highly potentiated in the presence of bicarbonate, 128- and 256-fold, respectively against E. coli (Figure 4B,C), and 16- and 256-fold, respectively against S. aureus (Table S5). Also enhanced in the presence of bicarbonate, was the activity of the porcrine leukocyte protegrin (8-fold in both E. coli and S. aureus) (Figure 4D, Table S5). Additionally, a physiological concentration of sodium bicarbonate enhanced the inhibitory activity of other innate immunity chemical factors such as lysozyme and bile salts against E. coli (Figure 4F,G). Interestingly, the innate immunity chemical barrier, hyaluronic acid, which is ubiquitously expressed in the extracellular matrix of all vertebrate tissues was also highly potentiated in the presence of sodium bicarbonate, 64-fold in both E. coli and S. aureus (Figure 4H, Table S5). Common among these components of innate immunity is their ultimate action on the cytoplasmic membrane causing membrane depolarization, suggesting for the first time, a role for bicarbonate as a mediator of membrane attack. Indeed, the majority of innate immunity constituents tested herein are ultimately perturbants of membrane potential37-40, suggesting a concerted attack by the host on bacterial PMF using these factors in bicarbonate-rich environment. Overall, our studies of innate immune components suggested that sodium bicarbonate is intrinsically antibacterial and an integral player in immunity, working in synergy with physical and chemical barriers to eliminate pathogens that cause infection."


A Spoonful of Baking Soda Helps the Antibiotics Go Down? | American Council on Science and Health
"...An article in the American Chemical Society Infectious Disease suggests we have overlooked a means of treating sepsis that our body already provides, bicarbonate. It is important to note that the research involves in vitro work only."

"...Their experiments demonstrate that at physiologic concentrations, bicarbonate enhanced the activity of some antibiotics. More importantly, with respect to sepsis, bicarbonate potentiated the impact of antibiotics on four of the bacterial species identified by the World Health Organization as global health priorities. [2] This effect was not related to an increase in pH, which was adjusted to remain physiologically normal. Their hypothesis for these findings was that bicarbonate interfered with the energy available to bacteria, by altering what is known as the proton motive force (PMF), an electrochemical gradient across the bacterial cell wall that bacteria harness to make energy. Bicarbonate interferes with this gradient, and this can influence how antibiotic molecules behave. For instance, the PMF is directly related to pumps that bacteria possess in their cell membranes. Tetracycline penetrates cell walls based on a pH gradient, but bicarbonate reduces the gradient, reducing tetracycline's effect as measured by MICs. As bicarbonate reduces the pH gradient, bacteria compensate by increasing the electrical gradient. Aminoglycosides' activity is more related to electrical charge, and bicarbonate enhances the entry of aminoglycosides as measured by MICs. Additionally, under normal physiologic concentrations, bicarbonate seems to make it more difficult for bacteria like E. coli to produce energy, resulting in slower growth. Slower growth means that antibiotics that act when bacteria are actively dividing become less effective. Furthermore, their research suggested that bicarbonate modulates portions of our immune response and can have impacts on antibiotics that we fail to recognize from simple in vitro testing. The authors believe these experiments can direct research into new antimicrobial drugs and therapies. But as a clinician, I think the experimental findings point towards a more immediate use for bicarbonate, as well (e.g. sepsis treatment)."
 

Koveras

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Thanks @haidut

I was organizing a few things around sepsis the other day for those interested

Note last quote on thiamin regarding your thoughts above

Serotonin

Bazarevich, G., Deviataev, A. M., Likhtenshtein, A. O., Natsvlishvili, B. P., & Sadeko, M. (1976). [Role of the biological activity of serotonin in the production of the "shock lung" syndrome]. Biull Eksp Biol Med, 82(10), 1181-1183.

Zhang, J., Bi, J., Liu, S., Pang, Q., Zhang, R., Wang, S., & Liu, C. (2017). 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice. Mediators Inflamm, 2017, 6374283. doi:10.1155/2017/6374283

"In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis."​

Cyproheptadine

Almqvist, P., Kuenzig, M., & Schwartz, S. I. (1983). The effect of naloxone and cyproheptadine on pulmonary platelet trapping, hypotension, and platelet aggregability in traumatized dogs. J Trauma, 23(5), 405-407.

"Adult respiratory distress syndrome (ARDS) is a serious complication of trauma and sepsis. We have earlier shown naloxone, an opiate antagonist, and cyproheptadine, an antiserotonin drug, to be effective in reducing pulmonary platelet trapping (PPT), which is thought to play an important role in the evolution of ARDS in endotoxin-shocked dogs. Endorphins are implicated as pathophysiologic factors in shock, and serotonin is a possible mediator of their action. The present study shows naloxone and cyproheptadine to be equally effective in protecting against PPT in dogs subjected to trauma, and when naloxone is given before the trauma it also obviates the hypotension associated with trauma. In addition, the naloxone- and cyproheptadine-treated animals did not show the increased platelet aggregability usually seen in traumatized dogs."
Almqvist, P., Skudder, P., Jr., Kuenzig, M., & Schwartz, S. I. (1984). Effect of cyproheptadine on endotoxin-induced pulmonary platelet trapping. Am Surg, 50(9), 503-505.

"Posttreatment with cyproheptadine obviated [Pulmonary platelet trapping] indicating the applicability of cyproheptadine in the treatment of ARDS. Pretreated dogs had PPT not significantly different from endotoxin controls, suggesting that blocking of serotonin before shock activates other vasoactive substances, which may include prostaglandins or prostaglandin derivates."
Wang, L., Zhang, Q., Hu, X., Lun, N., Wang, B., & Zhu, F. (2002). Anti-endotoxic shock effects of cyproheptadine in rats. Chin Med J (Engl), 115(3), 443-445.

“[Cyproheptadine] exerts an anti-endotoxic shock effect by inhibiting TNF(alpha) gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing [Ca(2+)](i) overload.”
Wang, L. Z., Liu, Y. Q., Cui, Y. H., Zhu, F. H., Wang, B. S., & Lun, N. (1999). Effects of dexamethasone, cyproheptadine, anisodamine, and dinoprostone on TNF alpha production in endotoxic shock. Zhongguo Yao Li Xue Bao, 20(2), 171-174.
Tryptophan Metabolism

Schefold, J. C., Zeden, J. P., Pschowski, R., Hammoud, B., Fotopoulou, C., Hasper, D., . . . Reinke, P. (2010). Treatment with granulocyte-macrophage colony-stimulating factor is associated with reduced indoleamine 2,3-dioxygenase activity and kynurenine pathway catabolites in patients with severe sepsis and septic shock. Scand J Infect Dis, 42(3), 164-171. doi:10.3109/00365540903405768

"Metabolites downstream of IDO (kynurenine, quinolinic acid, kynurenic acid) were all induced in sepsis and declined in the [granulocyte-macrophage colony-stimulating factor] group, but not in controls.”
Zeden, J. P., Fusch, G., Holtfreter, B., Schefold, J. C., Reinke, P., Domanska, G., . . . Schuett, C. (2010). Excessive tryptophan catabolism along the kynurenine pathway precedes ongoing sepsis in critically ill patients. Anaesth Intensive Care, 38(2), 307-316.

"It has recently been shown that an increased plasma level of the tryptophan catabolite kynurenine is an early indicator for the development of sepsis in major trauma patients.” … " In general, non-septic critically ill patients showed activation of the kynurenine pathway, but septic shock coincided with an exacerbation of kynurenine pathway activity even in the absence of renal failure. Importantly, plasma concentrations of quinolinic acid (area under the curve 0.832 [95% confidence interval 0.710 to 0.954]) and the Quin/Trp ratio (area under the curve 0.835 [95% confidence interval; 0.719 to 0.952]) showed the best discrimination between non-septic and pre-septic patients at baseline."​

Vitamin C / Hydrocortisone / Thiamin

Barabutis, N., Khangoora, V., Marik, P. E., & Catravas, J. D. (2017). Hydrocortisone and Ascorbic Acid Synergistically Prevent and Repair Lipopolysaccharide-Induced Pulmonary Endothelial Barrier Dysfunction. Chest, 152(5), 954-962. doi:10.1016/j.chest.2017.07.014

"LPS alone induced profound hyperpermeability, as reflected in decreased values of transendothelial electrical resistance. vitC alone did not exhibit barrier enhancement properties nor did it affect the LPS-induced hyperpermeability. Similarly, HC alone exhibited only a minor barrier-enhancing and protective effect. Conversely, the combination of HC and vitC, either as before or after treatment, dramatically reversed the LPS-induced barrier dysfunction"
Marik, P. E., Khangoora, V., Rivera, R., Hooper, M. H., & Catravas, J. (2017). Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest, 151(6), 1229-1238. doi:10.1016/j.chest.2016.11.036

"Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine, are effective in preventing progressive organ dysfunction, including acute kidney injury, and in reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings.”​

Thiamin

Collie, J. T. B., Greaves, R. F., Jones, O. A. H., Lam, Q., Eastwood, G. M., & Bellomo, R. (2017). Vitamin B1 in critically ill patients: needs and challenges. Clin Chem Lab Med, 55(11), 1652-1668. doi:10.1515/cclm-2017-0054

Holmberg, M. J., Moskowitz, A., Patel, P. V., Grossestreuer, A. V., Uber, A., Stankovic, N., . . . Donnino, M. W. (2018). Thiamine in septic shock patients with alcohol use disorders: An observational pilot study. J Crit Care, 43, 61-64. doi:10.1016/j.jcrc.2017.08.022

Moskowitz, A., Andersen, L. W., Cocchi, M. N., Karlsson, M., Patel, P. V., & Donnino, M. W. (2017). Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial. Ann Am Thorac Soc, 14(5), 737-741. doi:10.1513/AnnalsATS.201608-656BC

"In this post hoc analysis of a randomized controlled trial, patients with septic shock randomized to receive thiamine had lower serum creatinine levels and a lower rate of progression to RRT than patients randomized to placebo. These findings should be considered hypothesis generating and can be used as a foundation for further, prospective investigation in this area."
Sassoon, C. S., Zhu, E., Fang, L., Subramanian, V. S., & Said, H. M. (2016). Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis. Crit Care Med, 44(9), e875-881. doi:10.1097/CCM.0000000000001745

"For the first time, we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and mitochondrial thiamin pyrophosphate transporter, leading to adenosine triphosphate depletion.”​
 
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Travis

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Thanks @haidut
Tryptophan Metabolism

"It has recently been shown that an increased plasma level of the tryptophan catabolite kynurenine is an early indicator for the development of sepsis in major trauma patients.” … " In general, non-septic critically ill patients showed activation of the kynurenine pathway, but septic shock coincided with an exacerbation of kynurenine pathway activity even in the absence of renal failure. Importantly, plasma concentrations of quinolinic acid (area under the curve 0.832 [95% confidence interval 0.710 to 0.954]) and the Quin/Trp ratio (area under the curve 0.835 [95% confidence interval; 0.719 to 0.952]) showed the best discrimination between non-septic and pre-septic patients at baseline."​
I did read an article showing that endotoxin will increase γ-interferon. This is one cytokine that I know induces tryptophan dioxygenase and generally view it as the worst one. Cytokines all seem to have slightly different functions and induce different enzymes, with some overlap in function between some of them.

This low tryptophan is probably why grains and some infections can make people weak. Through the enzyme tryptophan dioxygenase, interferon-γ has been shown to reduce serum tryptophan levels by 50% while having no significant effect on other plasma amino acids. Besides histamine and exorphins, this is another way in which some food proteins can powerfully effect psychology.

"...Importantly, the chemical bicarbonate was uniquely responsible for the enhancements observed. The activity was not due to a trivial effect on pH. [...] ...Accordingly, we observed a profound effect on cellular respiration (70% reduction) in E. coli treated with 25 mM sodium bicarbonate [...] Overall, these experiments suggest that bicarbonate is a bacteriostatic compound that perturbs cellular respiration and reduces the activity of cell wall-active antibiotics that require actively growing bacteria for activity. Chemical genomics studies further reveal action of bicarbonate on the proton motive force. [...] ...Finally, decreased promoter activity was also observed for many ATP-dependent processes, likely as an adaptive effort to conserve energy. Overall, E. coli adaptation to bicarbonate involved strategies to respond to periplasmic pH changes, increase membrane potential and preserve energy. Bicarbonate selectively dissipates the transmembrane pH gradient. [...] This effect was not related to an increase in pH, which was adjusted to remain physiologically normal. Their hypothesis for these findings was that bicarbonate interfered with the energy available to bacteria, by altering what is known as the proton motive force (PMF), an electrochemical gradient across the bacterial cell wall that bacteria harness to make energy. Bicarbonate interferes with this gradient, and this can influence how antibiotic molecules behave. For instance, the PMF is directly related to pumps that bacteria possess in their cell membranes.
I wonder if this has anything to do with increased CO₂ adsorbing onto proteins? Carbon dioxide has been shown to be adsorbed onto polyarginine, making you wonder if this would decrease the activity of iNOS and arginase? I think Ray Peat talks a little about CO₂ adsorbing onto proteins at the N‐containing side chains.

There are a few ways that I know of to decrease mitochondrial respiration. Cyanide adsorbs onto heme iron, lowering electron flux and mitochondrial membrane potential that way. Carbon monoxide is also known to bind heme and slow respiration, but I'm not sure about carbon dioxide.. .

Carbonate is also a water‐soluble anion which could affect K⁺ dynamics, an ion known to complex‐with and stabilize ATP.
 

Diokine

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This is one cytokine that I know induces tryptophan dioxygenase

Endotoxin insult will actually block the activity of tryptophan dioxygenase, I think through disruption of RNA synthesis via amino acid metabolism derangement.

I wonder if this has anything to do with increased CO₂ adsorbing onto proteins?

I think this is exactly right - it's been shown that animals fed a diet containing excessive leucine will have higher levels of tryptophan oxygenase in their livers. Endotoxin severely disrupts the incorporation and processing of amino acids, and I think the bicarbonate acts to stabilize the proteins.
 
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If they kept pH constant, does that mean intact baking soda might not work?
 

Travis

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Endotoxin insult will actually block the activity of tryptophan dioxygenase, I think through disruption of RNA synthesis via amino acid metabolism derangement.
Endotoxin induces the expression of indolamine dioxygenase in the brain:

Lestage, J. "The enzyme indoleamine 2, 3-dioxygenase is induced in the mouse brain in response to peripheral administration of lipopolysaccharide and superantigen." Brain, behavior, and immunity (2002)

'Peripherally injected LPS had been demonstrated to activate the KYN pathway in the mouse brain (Heyes et al., 1989).' ―Lestage

'The present study aimed at evaluating the effects of a peripheral treatment with lipopolysaccharide (LPS) from Escherichia coli, a Gram-negative bacteria, and enterotoxin B from Staphylococcus aureus (SEB), a Gram-positive bacteria, on IDO activity in the brain of two strains of mice, CD1 and BALB/c, differing by their Th1/Th2 balance.' ―Lestage

They measured the total activity of the enzymes using tryptophan as substrate; they had detected kynurenine by UV absorption (365·nm):

'The supernatants (0.2 ml) were added to 0.8 ml of the reaction mixture containing 400 μM L-tryptophan, 20 mM ascorbate, 10 μM methylene blue, and 100 μg catalase in 50 mM potassium phosphate buffer pH 6.5. The reaction was carried out at 37°C under agitation for 60 min. Then, it was blocked by adding 0.2 ml of 30% trichloroacetic acid and further incubated at 50°C for 30 min to convert the N-formylkynurenine to L-kynurenine. Samples were centrifuged at 13,000g for 10 min at 4°C. The supernatants were filtered through microspin ultrafiltrates with a cut-off of 10,000M before being taken for measurement of IDO. The amount of L-kynurenine formed from tryptophan was determined by reversed phase high pressure liquid chromatography (HPLC) (Holmes, 1988).. .' ―Lestage

IDO.png
'Blood was allowed to clot and serum collected after centrifugation. Sera were kept at )80 C until assay. The serum concentrations of IFN-γ were determined by a commercially available ELISA (Pharmingen).' ―Lestage
They had measured the predictable interferon-γ spike, and also the increase in indolamine dioxygenase that should follow.

I couldn't find any information on LPS inhibing tryptophan dioxygenase in the liver.
 

haidut

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leading to adenosine triphosphate depletion

Thanks for all of these links.
So, the main danger of sepsis is the systemic depletion of ATP?? I wonder if giving ATP through IV would help even more than thiamine...
 

haidut

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There are a few ways that I know of to decrease mitochondrial respiration. Cyanide adsorbs onto heme iron, lowering electron flux and mitochondrial membrane potential that way. Carbon monoxide is also known to bind heme and slow respiration, but I'm not sure about carbon dioxide.. .

This study shows that bicarbonate stimulates succinate dehydrogenase even more so then succinic acid. I guess effects of bicarbonate on metabolism may depend on pH??
Activation of succinate dehydrogenase by bicarbonate - ScienceDirect
 

managing

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If they kept pH constant, does that mean intact baking soda might not work?
The abstract doesnt specify how they administered the antiB or bicarb. One would presume orally. In which case, the only thing bicarb would do is neutralize some stomach acid. In extreme, that could effect the adsorption, but I think most antiB pass through the stomach unaltered anyway?
 

Vinero

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How do you guys take baking soda? Just dissolve in orange juice? Or is water better ? I have never used baking soda before but this post made me buy a pack of it.
 

Seleniodine

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I am curious if this effect would apply to other bicarbonates such as magnesium or potassium? Also , would consuming say magnesium bicarbonate water with mildly antibiotic foods such as carrot salad or Cascara and Pau D'arco bark extracts have a similar synergistic result. Thanks for the great research and info Haidut!

Furthermore, it was the bicarbonate ion that was responsible for all of these effects, not sodium or other metal salts tested.
 
Last edited:

Koveras

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Thanks for all of these links.
So, the main danger of sepsis is the systemic depletion of ATP?? I wonder if giving ATP through IV would help even more than thiamine...

Would like to see this with the intervention given after the endotoxin however...

Crit Care Med. 1998 Feb;26(2):322-37.
Effects of adenosine on cardiopulmonary functions and oxygen-derived variables during endotoxemia.
Thiel M1, Kreimeier U, Holzer K, Moritz S, Peter K, Messmer K.

OBJECTIVES:
To determine the effects of a prophylactic intravenous infusion of adenosine on cardiopulmonary functions and oxygen-derived variables in a porcine model of endotoxemia.​
DESIGN:
Prospective, randomized, placebo-controlled, unblinded study.​
SETTING:
University research laboratory.​
SUBJECTS:
Thirty country bred pigs, aged 6 to 7 wks, weighing 24.9 +/- 0.65 (SEM) kg body weight.​
INTERVENTIONS:
Pigs were anesthetized by i.v. pentobarbital and fentanyl, intratracheally intubated, and mechanically normoventilated with a gas mixture of nitrous oxide/oxygen = 1:1. Intravascular catheters were inserted to allow for determination of arterial, central venous blood pressure, pulmonary artery occlusion pressure, cardiac output, and sampling of blood for gas analyses. Group 1 (n = 10) received a 330-min intravenous infusion of Salmonella abortus equi endotoxin (5 microg/kg body weight x hr). Group 2 (n = 10) received an additional intravenous infusion of adenosine (150 microg/kg body weight x min), started 30 mins before the infusion of endotoxin. Control groups 3 and 4 (n = 5 for both groups) received adenosine or physiologic saline, respectively.​
MEASUREMENTS AND MAIN RESULTS:
Parameters of cardiopulmonary function and oxygen-derived variables were calculated from pulmonary artery catheter measurements and blood gas analyses using standard formula. Plasma concentrations of purine compounds (adenosine, inosine, hypoxanthine) were determined by high-performance liquid chromatography. Since tumor necrosis factor-alpha plays a central role in the development of endotoxic shock, concentrations of this cytokine were determined in serum by enzyme-linked immunosorbent assay. Infusion of adenosine before the beginning of the infusion of endotoxin increased plasma concentrations of the nucleoside from 193 +/- 72 to 553 +/- 65 nmol/L and decreased the systemic vascular resistance by 50%. Although acting as a potent vasodilator under control conditions, adenosine did not aggravate the arterial hypotension elicited by endotoxemia but significantly increased cardiac output by a comparably small decrease in systemic vascular resistance, prevention of pulmonary vasoconstriction, and improvement of left ventricular performance. Despite significant pulmonary vasodilation, gas exchange was not worsened but slightly improved by adenosine. With the increase in cardiac output and arterial oxygenation, systemic oxygen delivery almost doubled. This adenosine-induced oxygen flux was not a surplus but was most likely utilized by tissues, as suggested by the much earlier beginning of the increase in the systemic oxygen consumption and the attenuation of the decrease in the gastric mucosal pHi. No effects of adenosine were observed on the endotoxin-induced increase in serum concentrations of tumor necrosis factor-alpha.​
CONCLUSIONS:
Infusion of adenosine might be useful to improve flow-dependent oxygen delivery and tissue oxygenation during endotoxic shock without the induction of adverse cardiopulmonary side effects. The beneficial hemodynamic effects of adenosine appear not to be mediated by the inhibition of the release of tumor necrosis factor-alpha.​
 

Koveras

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Thanks for all of these links.
So, the main danger of sepsis is the systemic depletion of ATP?? I wonder if giving ATP through IV would help even more than thiamine...

This one gives some clues as well

Crit Care. 2008;12(5):R125. doi: 10.1186/cc7033. Epub 2008 Oct 13.
The adenosine deaminase inhibitor erythro-9-[2-hydroxyl-3-nonyl]-adenine decreases intestinal permeability and protects against experimental sepsis: a prospective, randomised laboratory investigation.
Kayhan N1, Funke B, Conzelmann LO, Winkler H, Hofer S, Steppan J, Schmidt H, Bardenheuer H, Vahl CF, Weigand MA.

INTRODUCTION:
The treatment of septic conditions in critically ill patients is still one of medicine's major challenges. Cyclic nucleotides, adenosine and its receptors play a pivotal role in the regulation of inflammatory responses and in limiting inflammatory tissue destruction. The aim of this study was to verify the hypothesis that adenosine deaminase-1 and cyclic guanosine monophosphate-stimulated phosphodiesterase inhibition by erythro-9-[2-hydroxyl-3-nonyl]-adenine could be beneficial in experimental endotoxicosis/sepsis.​
METHOD:
We used two established animal models for endotoxicosis and sepsis. Twenty-four male Wistar rats that had been given intravenous endotoxin (Escherichia coli lipopolysaccharide) were treated with either erythro-9-[2-hydroxyl-3-nonyl]-adenine infusion or 0.9% saline during a study length of 120 minutes. Sepsis in 84 female C57BL/6 mice was induced by caecal ligation and puncture. Animals were treated with repeated erythro-9-[2-hydroxyl-3-nonyl]-adenine injections after 0, 12 and 24 hours or 4, 12 and 24 hours for delayed treatment.​
RESULTS:
In endotoxaemic rats, intestinal production of hypoxanthine increased from 9.8 +/- 90.2 micromol/l at baseline to 411.4 +/- 124.6 micromol/l and uric acid formation increased from 1.5 +/- 2.3 mmol/l to 13.1 +/- 2.7 mmol/l after 120 minutes. In endotoxaemic animals treated with erythro-9-[2-hydroxyl-3-nonyl]-adenine, we found no elevation of adenosine metabolites. The lactulose/L-rhamnose ratio (14.3 versus 4.2 in control animals; p = 2.5 x 10(-7)) reflects a highly permeable small intestine and through the application of erythro-9-[2-hydroxyl-3-nonyl]-adenine, intestinal permeability could be re-established. The lipopolysaccharide animals had decreased L-rhamnose/3-O-methyl-D-glucose urine excretion ratios. Erythro-9-[2-hydroxyl-3-nonyl]-adenine reduced this effect. The mucosa damage score of the septic animals was higher compared with control and therapy animals (p < 0.05). Septic shock induction by caecal ligation and puncture resulted in a 160-hour survival rate of about 25%. In contrast, direct adenosine deaminase-1 inhibition resulted in a survival rate of about 75% (p = 0.0018). A protective effect was still present when erythro-9-[2-hydroxyl-3-nonyl]-adenine treatment was delayed for four hours (55%, p = 0.029).
CONCLUSIONS:
We present further evidence of the beneficial effects achieved by administering erythro-9-[2-hydroxyl-3-nonyl]-adenine, an adenosine deaminase-1 and cyclic guanosine monophosphate-stimulated phosphodiesterase inhibitor, in an endotoxicosis and sepsis animal model. This suggests a potential therapeutic option in the treatment of septic conditions.​
 

Xisca

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I am curious if this effect would apply to other bicarbonates such as magnesium or potassium? Also , would consuming say magnesium bicarbonate water with mildly antibiotic foods such as carrot salad or Cascara and Pau D'arco bark extracts have a similar synergistic result. Thanks for the great research and info Haidut!
Yes why only sodium bicarb? What if you already have much enough sodium?
Anyway it depends the length of use too...
 

Pompadour

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May 11, 2017
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Before PPI;s people often took bicarbonate as a remedy for GERD. My father took it routinely very often ... but i can't say that it helped his problems (he struggled with long standing liver problems, with depression , etc.)
 

Soren

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physiological concentration of 25 mM.

What is the dose to get to a concentration of 25nm baking soda as was done in the study?

I was thinking about taking a Tablespoon in a glass of water or orange juice everyday.
 

Mossy

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Jun 2, 2017
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What is the dose to get to a concentration of 25nm baking soda as was done in the study?

I was thinking about taking a Tablespoon in a glass of water or orange juice everyday.
Should you take that much, I’d be curious to see how you do. I took half of that once, post workout, after reading a pro-Peat write-up, and it did a number on me. Just did not feel well for a few days. I have subpar health, so maybe you’ll be ok.
 

Soren

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Should you take that much, I’d be curious to see how you do. I took half of that once, post workout, after reading a pro-Peat write-up, and it did a number on me. Just did not feel well for a few days. I have subpar health, so maybe you’ll be ok.

I took that much and a really weird thing happened. I had a massive craving for sugar and water. I drank 4 cans of coke in about an hour. Other than that I felt a bit weird but not bad.
 

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