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Showing posts with label M2. Show all posts
Showing posts with label M2. Show all posts

Friday 4 May 2018

Drinking Baking Soda for Vagal Nerve Stimulation?













 The easy to read article: -


 The original paper:-

There are several posts in this blog about Vagal Nerve Stimulation, which may look like science fiction, but does have potent anti-inflammatory effects.  What if you could achieve some of those benefits in a much simpler, non-invasive way? And all in the name of actual science.

Many people currently take baking soda (sodium bicarbonate) for all kinds of different reasons. It is the bicarbonate (HCO3) that is the interesting part.

Bicarbonate is alkaline and it plays a key role in how the body regulates pH; above 7 is alkaline and below 7 is acidic. The other important factors are carbonic acid, carbon dioxide and water. The body is constantly having to maintain its pH in a narrow range. Sometimes this is not possible, as we saw in the case of long distance runners, the mitochondria in their muscles run out of enough oxygen and then lactic acidosis occurs. This drop in pH causes some side effects which in theory can be reduced if you increase bicarbonate in your bloodstream by consuming baking soda.
Many products for heartburn and indigestion contain baking soda to provide a short-term reduction in acidity. Some people just mix regular baking soda with a glass of water.
Many people seem to use baking soda to treat gout, which is caused by high levels of uric acid, but many do seem to worry about elevating their blood pressure. This is because of the sodium in baking soda.
Some people take baking soda long term to improve their sleep. This actually appears to be a DAN therapy.
Some people with autism are taking baking soda for all kinds of reasons other than poor sleep, including for allergy.

Kidney Disease and Baking Soda
I was surprised to see that baking soda has been shown in numerous studies to be beneficial for those with kidney disease; until very recently nobody really knew why it helps. Baking soda will reduce the pH of urine and some bicarbonate supplements even include pH measuring strips.
A recent study set out to investigate why baking soda has this positive effect and it came up with some very interesting conclusions. The bicarbonate is producing an anti-inflammatory effect very similar to that produced by vagal nerve stimulation (VNS). As we have seen in previous posts, by stimulating the vagus nerve you activate the cholinergic anti-inflammatory pathway. The problem with VNS is that you need a device connected to your vagus nerve to deliver electrical pulses to it. This exists today and special versions are being developed to treat arthritis. Half a teaspoon of baking soda in a glass of water is a much simpler therapy.

We speculate that the anti-inflammatory effects of oral NaHCO3 ingestion are mediated by activation of the cholinergic ant-inflammatory pathway. The cholinergic anti-inflammatory pathway has been reported to be the efferent arm of the anti-inflammatory reflex, which acts via vagal efferents to promote M2 macrophage polarization in the spleen and limit activation of the innate immune system, thereby preventing damage caused by excessive cytokine production. Inflammatory macrophages and excessive TNF-a production have been implicated in the pathology of a broad range of disease states, including rheumatoid arthritis, cardiovascular disease, atherosclerosis, irritable bowel disease, type 2 diabetes, and neurodegenerative diseases as well as others. Conversely, FOXP3+ Tregs have been shown to be beneficial in a wide range of pathologies. FOXP3+ Tregs act to suppress activation of the immune system and induce immune tolerance. Evidence suggests that expansion of Tregs may be beneficial in a wide variety of disease states that involve pathological activation of the immune system, including allergy, asthma, multiple sclerosis (29), graft versus host disease, diabetes, and hypertension as well as many others. Given its therapeutic potential against inflammatory disease, there is currently much interest in methods to activate the cholinergic anti-inflammatory pathway.”

Macrophage polarization
This section is a cut and paste from the site below:


Chronic inflammation is currently linked to a variety of diseases. The disease processes include the central nervous system through Rheumatoid Arthritis. The macrophages of the brain (microglia) and the peripheral innate immune system become chronically activated and release inflammatory cytokines. These cytokines cause tissue damage and cell death.
Macrophages function as control switches of the immune system, providing a balance between pro- and anti-inflammatory responses. To accomplish this, they develop into different subsets: classically (M1) or alternatively (M2) activated macrophages.
M1 macrophages display a cytotoxic, proinflammatory phenotype, much like the soldiers of The Dark Side of The Force in the Star Wars movies. M2 macrophages, like Jedi fighters, suppress immune and inflammatory responses and participate in wound repair and angiogenesis.
Critical to the actions of these divergent or polarized macrophage subpopulations is the regulated release of inflammatory mediators. When properly controlled, M1 macrophages effectively destroy invading pathogens, tumor cells and foreign materials. However, when M1 activation becomes excessive or uncontrolled, these cells can succumb to The Dark Side, releasing copious amounts of cytotoxic mediators that contribute to disease pathogenesis.
The activity of M1 macrophages is countered by The Force of alternatively activated M2 macrophages, which release anti-inflammatory cytokines, growth factors and mediators involved in extracellular matrix turnover and tissue repair.
It is the balance in the production of mediators by these two macrophage subpopulations that ultimately determines the outcome of the tissue response to chemical toxicants. 





 Baking Soda and Macrophage Polarization 
The recent research showed that oral bicarbonate reduced M1 macrophages and increased M2 macrophages, in a dose dependent fashion; so shifting away from the Dark Side towards the Jedi Order.

The above is for rats, but he same very likely applies to humans. 

So is baking soda a panacea for auto-immune disease?
The big drawback of baking soda is that very often causes irritation to your digestion, but this should also apply to those indigestion tablets containing baking soda.
These tablets do not just contain sodium bicarbonate, they often contain potassium bicarbonate. It has been reported that the effect of drinking sodium bicarbonate will affect your blood electrolytes as follows
·        Raise sodium (and hence potentially blood pressure)

·        Raise calcium

·        Lower potassium

·        Raise bicarbonate

·        Lower chloride

In another study below in the use of baking soda in humans (table III in the full paper) the level of potassium fell 10%, from 4.3 to 3.9 mmol/l. Sodium did not change much at all.


So adding potassium bicarbonate is quite clever. It will naturally increase potassium but it has a negative effect on sodium.
Some DAN-type doctors use Alka Seltzer Gold, which contains
Anhydrous citric acid 1000 mg
Potassium bicarbonate 344 mg
Sodium bicarbonate  1050 mg

Here is what Dr Sidney Baker writes on ARI’s website 

A quarter of an Alka Seltzer Gold tablet for a toddler or two tablets for an adult, dissolved in a glass of water, is safe when given once or twice in a day to see its effect. In the context of sleep problems its first use is just to see if it does work. If it does—in, say, less than 35 minutes—then you’ve learned a lot and done some good. What you have learned is that there was something that didn’t agree with the person to whom it was administered. The good you have done is to find a temporary solution to the problem and take steps based on what you have learned.” 

Potassium bicarbonate is an approved food additive often used in making wine.  Club soda usually contains potassium bicarbonate. In the European Union, it is identified by the E number E501.
Some people with high blood pressure self-treat with potassium bicarbonate.
You will struggle to find Alka Seltzer Gold outside North America, but you can easily make your own.
It looks like the researchers at Augusta University have put some science behind Dr Baker’s therapy. If an adult keeps taking two of these Aka Seltzer Gold tablets a day, he will tamp down his immune system. If he has any kind of autoimmune condition, this would appear as an improvement in the symptoms he was accustomed to.
Most people with autism do seem to have auto-immune comorbidities of one kind or another which would be expected to make their autism symptoms worse.
So it is pretty clear what one of those North American autism researchers needs to do. Find the bicarbonate product that causes the least GI problems and test it on people with autism and an auto-immune comorbidity (asthma, allergy, irritable bowel syndrome etc). The results would be interesting. 
If you read the full text of the paper you will see that the researcher’s still do not fully understand what is going on.
It is currently fashionable to talk about alkalinity and how it is good for you, but there is much more to it than this idea. Baking soda does reduce acidity, but so do drugs called Proton Pump Inhibitors (e.g. Nexium) and H2 antihistamines (Zantac), these drugs do not activate the cholinergic ant-inflammatory pathway. Worse still the researchers showed that by taking a Proton Pump Inhibitor (e.g. esomeprazole, below), you blocked the clever anti-inflammatory effect of baking soda. You need acid (H+) to be present.
In the chart below we want as much M2 as possible and as little M1. This is only achieved by bicarbonate alone.



So, people with IBS will not benefit from this bicarbonate effect unless they stop taking their Nexium/Zantac/ …prazole.


Conclusion
A combination of sodium bicarbonate (baking soda) and potassium bicarbonate (a food additive) equal to about 2g dissolved in a water bottle and drunk either at once, or throughout the day, would be a good trial for those autism researchers to think about. They would have to make sure no drugs were being used to inhibit the production of gastric acids, so no H2 antihistamines or more modern PPIs allowed; they will stop the anti-inflammatory effect.
It also looks like marathon runners might benefit from taking Alka Seltzer Gold, unless it counts as a banned substance.
Drinking your baking soda slowly apparently reduces the incidence of GI problems. 
Long term use of Proton Pump Inhibitors, like Nexium, to lower stomach acidity, may have the unintended consequence of aggravating auto-immune disease.

=========


The original paper


Some highlights:- 
Participants. To examine the effects of NaHCO3 on acute changes in parasympathetic activity, 12 healthy participants (six men, six women, age 27 6 2 y, body mass index [BMI] 25.3 6 1.2 kg/m2) were provided 2 g of NaHCO3 dissolved in 250 ml of bottled water (treatment [TXT] group).
An additional six participants (four men, two women, age 25 6 1, BMI 25.7 6 2.1 kg/m2) were recruited as controls and were provided 1.39 g of NaCl (equivalent molar load to 2 g of NaHCO3) dissolved in 250 ml of bottled water (CON group).
 Serum electrolytes. Blood samples were collected via an i.v. catheter (Nexiva; Becton Dickinson, Franklin Lakes, NJ) at baseline and at 60 min intervals posttreatment to examine changes in serum electrolyte balance (Na, K, and Cl2). Analytical flow cytometry (humans). In the NaHCO3 TXT group, 10 of 12 subjects had blood drawn at 3 h posttreatment. Blood was taken at all time points for all control subjects. No data were excluded from the analysis. Flow cytometric analysis of heparinized whole blood was performed as described previously (11–13). Briefly, cells were incubated with Abs for surface markers (15 min on ice in dark) before incubation with Abs against intracellular cytokines and factors (after permeabilization for 15 min using fix/Perm mixture; eBioscience), including CD11b, CD68, TNF-a (for M1 macrophages); CD11b, CD68, CD206 and IL-10 (for M2 macrophages) (purchased from BD BioSciences); and CD16 and TNF-a (for neutrophils; from eBioscience). 

To determine whether oral NaHCO3 had a similar antiinflammatory action in humans as we found in rats, we evaluated blood samples at baseline and 1, 2, and 3 h following ingestion of a single dose (2 g) of NaHCO3 (n = 11) or equimolar NaCl (n = 6), each dissolved in 250 ml of bottled water. Pre- and posttreatment values of serum electrolytes are presented in Table III. There was a significant group by time interaction for changes in serum potassium (p = 0.029, h2 P = 0.279). Specifically, serum potassium decreased with NaHCO3 treatment (p = 0.008), but there was no change with NaCl treatment (p = 0.381). BMI and C-reactive protein levels were not significantly different at baseline between either group, indicating a similar baseline inflammatory state (Table IV). No other significant differences were observed between TXT groups at baseline in any variables tested (Table IV). Baseline flow cytometry values of all subjects, before ingesting NaHCO3 or NaCl in solution, are presented in Table IV. Prior to any treatment, the percentages of blood leukocytes that were TNFa+ neutrophils, M1 macrophages, or M2 macrophages were all significantly higher in the NaHCO3 TXT group when compared with baseline values obtained in the NaCl TXT group (Table IV). There was a significant TREATMENT 3 TIME effect on both M1 macrophages (p = 0.0004) and TNF-a–positive neutrophils (p = 0.0146), with the levels of these inflammatory cells in the plasma being reduced to a significantly greater degree following ingestion of NaHCO3 when compared with NaCl (Fig. 3). The greatest decreases in blood inflammatory cells were observed at 2 and 3 h following NaHCO3 ingestion. Similar to our observations in rats, oral NaHCO3 ingestion increased the percentage of blood leukocytes identified by flow cytometry as M2 macrophages (p = 0.00165) (Fig. 3). Decreases in inflammatory TNFa+ neutrophils and M1 macrophages in the NaHCO3 TXT group did not appear to be related to the differing baseline levels observed between TXT groups. When comparing individual responses between subjects of different groups, subjects with similar baseline levels of blood leukocytes responded differently if they received NaHCO3 compared with NaCl (Supplemental Fig. 1). Splenic involvement. In the current study, we found that, prior to beginning NaHCO3 or vehicle treatment, either complete removal of the spleen or simple manipulation of the spleen to midline during sterile surgical laparotomy completely abolished the effect of NaHCO3 to promote M1 to M2 polarization in the kidney of Dahl SS rats fed an HS diet for 2 wk (Fig. 4). Furthermore, both of these maneuvers resulted in a significant decrease in renal M2 macrophages when compared with sham laparotomy only (p = 0.02 and 0.0002, comparing laparotomy only to sham splenectomy and splenectomy for vehicle- and bicarbonate-treated groups, respectively; Fig. 4). We confirmed a functional antiinflammatory response using the MLR.  
In humans, efforts to stimulate the cholinergic anti-inflammatory pathway chronically by implanting stimulating electrodes on the vagal nerves have shown promise in patients with rheumatoid arthritis

Consistent with activation of the cholinergic anti-inflammatory pathway, in rats, removal of the spleen or treatment with the a7 nicotinic Ach receptor antagonist MLA abolished the anti-inflammatory effect of oral NaHCO3 intake. Our data indicate that oral NaHCO3 loading may provide a cheap, relatively safe, effective, and easily accessible and/or non-invasive method to activate cholinergic anti-inflammatory pathways in humans, which may be of benefit to patients suffering from a multitude of inflammatory disease states. As such, our findings could potentially have significant clinical application to the treatment of human disease. Future studies testing the efficacy of oral NaHCO3 to limit injury in models of inflammatory disease will be required to determine the therapeutic potential of this stimuli. 

We speculate that the anti-inflammatory effects of oral NaHCO3 ingestion are mediated by activation of the cholinergic antiinflammatory pathway. The cholinergic anti-inflammatory pathway has been reported to be the efferent arm of the anti-inflammatory reflex (15), which acts via vagal efferents to promote M2 macrophage polarization in the spleen and limit activation of the innate immune system, thereby preventing damage caused by excessive cytokine production (4, 16). Inflammatory macrophages and excessive TNF-a production have been implicated in the pathology of a broad range of disease states, including rheumatoid arthritis (17), cardiovascular disease (18), atherosclerosis (19, 20), irritable bowel disease (21), type 2 diabetes (22), and neurodegenerative diseases as well as others (23–26). Conversely, FOXP3+ Tregs have been shown to be beneficial in a wide range of pathologies. FOXP3+ Tregs act to suppress activation of the immune system and induce immune tolerance (27). Evidence suggests that expansion of Tregs may be beneficial in a wide variety of disease states that involve pathological activation of the immune system, including allergy (28), asthma (28), multiple sclerosis (29), graft versus host disease (30), diabetes (31), and hypertension (32, 33) as well as many others. Given its therapeutic potential against inflammatory disease, there is currently much interest in methods to activate the cholinergic anti-inflammatory.

Interestingly, we found that inhibition of gastric proton pumps prevented oral NaHCO3 from activating an anti-inflammatory response, suggesting that gastric H+ secretion is required. This finding may be particularly relevant to CKD, as long-term use of proton pump inhibitors has been associated with increased risk of developing CKD (36). 

Our data indicating that oral ingestion of NaHCO3 promotes an anti-inflammatory response, which is inhibited by an antagonist of the gastric proton pump, raises the possibility that the effect of vagal stimulation or denervation to promote or inhibit the anti-inflammatory response, respectively, is secondary to the common denominator between these stimuli: the stimulation of acid secretion in the stomach (53–55). This hypothesis is consistent with findings that Ghrelin, which also stimulates acid secretion, can activate the anti-inflammatory pathway (56). Our finding that mesothelial cells are required to mediate this anti-inflammatory response provides a potential sensory mechanism for this alternative hypothesis, whereby stomach acid secretion alters some factor within the peritoneal milieu, such as pH, that is sensed by the mesothelium that lines this compartment. Such a mechanism may be of physiological importance in deciphering whether Ags absorbed by the gut are inert (coming after a meal) or represent a potential infection of the peritoneum with ensuing acid production by invading bacteria and providing the appropriate response, either tolerance or inflammatory immune response, respectively. This alternative hypothesis challenges our current understanding of how vagal nerve stimulation promotes the cholinergic anti-inflammatory response in the spleen, suggesting for the first time that there may be no direct interface between the nervous and immune systems. In light of our data, further studies are warranted to determine whether promotion of an anti-inflammatory effect following stimulation of vagal nerves (classical activation of the cholinergic anti-inflammatory response) occurs independent of a requirement to stimulate stomach acid secretion. 

In summary, we report that oral NaHCO3 activates splenic anti-inflammatory pathways in both rats and humans. Our novel finding provides a potentially practical and/or cost-effective and relatively safe method to activate splenic anti-inflammatory pathways in humans and therefore may have significant therapeutic potential for inflammatory disease. We provide both functional (flow cytometry) and anatomical and histological evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal-like function of mesothelial cells. To our knowledge, this is the first evidence that mesothelial cells may have a role in transmitting cholinergic signals to distal sites and, combined with evidence that gastric acid secretion is required to promote an anti-inflammatory response to NaHCO3, raises the possibility that there may be no direct interface between the nervous and immune systems. Future studies testing the efficacy of oral NaHCO3 to limit injury in models of inflammatory disease will be required to determine the therapeutic potential of this stimuli.


PURPOSE:


This study investigated the effect of ingesting 0.3 g/kg body weight (BW) of sodium bicarbonate (NaHCO₃) on physiological responses, gastrointestinal (GI) tolerability, and sprint performance in elite rugby union players.

CONCLUSIONS: 
NaHCO₃ supplementation increased blood HCO₃⁻ concentration and attenuated the decline in blood pH compared with placebo during high-intensity exercise in well-trained rugby players but did not significantly improve exercise performance. The higher incidence and greater severity of GI symptoms after ingestion of NaHCO₃ may negatively affect physical performance, and the authors strongly recommend testing this supplement during training before use in competitive situations. 

Some ideas from Dr Baker over at ARI
https://www.autism.com/sleeplessness 

Alka Seltzer Gold and activated charcoal (in sequence—not mixed together!)
A dose of Alka Seltzer Gold followed in at least 20 minutes by a dose of activated charcoal provides information gained from seeing it work that is worth almost as much as the relief it provides. The equivalent of “Alka-Gold” comes in the form of tri-salts —sodium, magnesium, and potassium bicarbonate powder and capsules—from various nutritional supplement suppliers and compounding pharmacies. Alka Seltzer Gold (not Cold) contains only sodium and potassium bicarbonate. Not to be taken immediately after a large meal, it is safe and makes just about everything better. It is absorbed from the intestine quickly into the bloodstream and results in a slight, transient adjustment (called an alkaline tide) of the acidity that is associated with just about everything that goes wrong with us acutely and chronically when we are sick.


A quarter of an Alka Seltzer Gold tablet for a toddler or two tablets for an adult, dissolved in a glass of water, is safe when given once or twice in a day to see its effect. In the context of sleep problems its first use is just to see if it does work. If it does—in, say, less than 35 minutes—then you’ve learned a lot and done some good. What you have learned is that there was something that didn’t agree with the person to whom it was administered. The good you have done is to find a temporary solution to the problem and take steps based on what you have learned.



Unless the Alka Seltzer Gold is an instant success by itself, the next step in the sequence comes with the administration of activated charcoal. It comes as tablets (crushable) or encapsulated in doses of 100 to 560 mg. For individuals who cannot swallow capsules, the powder can be taken carefully from the capsules to avoid getting the powder on your clothing. It is, however, washable. If administered as a powder it must first be mixed in water. (Grape juice frozen concentrate— undiluted or minimally diluted—is a vehicle for children needing a strong disguise of taste and color, provided they can tolerate an exceptional bit of sugar.) A recipient who is likely to chew a capsule should be given the charcoal as a liquid suspension (water or juice) to avoid the risk of inhaling the fine black powder.

Many parents and individuals with problems discover from the use of charcoal for die-off reactions that it works—as just described—under circumstances that include just having a “bad day” or reactions to stresses such as allergenic foods, too much sugar, or alcohol, not enough sleep, or even just being hungry and irritable. Similar to Alka Seltzer Gold or its generic equivalent, activated charcoal works as a kind of panacea.


The risk that activated charcoal will absorb important nutrients is minimized by using it only for short-term diagnostic and treatment purposes and keeping it at least an hour away from foods and other medications. 

Here we have another DAN doctor using Alka Seltzer:-

4. FOOD ALLERGIES

Inflammation is a common result of the histamine release that takes place because of food allergies. Dr. Lendon Smith says children tend to crave what they are allergic to—dairy and wheat, for example. Many parents have seen dramatic changes when they not only reduce sugar and simple carbohydrates but when they start an allergy elimination diet, beginning with dairy items (not even one teaspoonful!). In a few weeks, they may also eliminate gluten products. For encouraging parent testimonials, go to www.gfcfdiet.com and www.blockcenter.com, and read Dr. Mary Ann Block’s success with elimination diets. Histamine is such a factor in behavior that Dr. Block recommends the use of Alka-Seltzer Gold (no medicine, just sodium and potassium), to help a child calm down from a tantrum or anxiety. A histamine reaction floods acid into the system, and this product serves to neutralize that acid, calming the body. A mother named Amy recently e-mailed me and thanked me for the suggestion of Alka-Seltzer Gold for her son Michael, age 10. When a meltdown or anxiety begins to occur (after all, no one can follow a diet perfectly), she goes “plop, plop, fizz, fizz,” and finds what a relief it is—for his nervous system.

For those of you interested to see what happens to your blood/urine when you take sodium/potassium bicarbonate, there is plenty of data in the full version of the paper below 

Previous studies demonstrated that the administration of NaHCO3 or sodium citrate had either only a small effect to reduce urinary Ca excretion or no effect, but that potassium citrate significantly reduced urinary Ca excretion. In order to further evaluate and compare the effects of NaHCO3 and of KHCO3, we performed ten metabolic balances in healthy men during 18 control days, 12 days of NaHCO3, 60 mmol/day and 12 days of KHCO3, 60 mmol/day. Six subjects were fed a low Ca diet (5.2 +/- 0.7 SD mmol/day) and three of these were also given calcitriol (0.5 microgram 6-hourly). Four subjects ate a normal Ca diet (19.5 +/- 1.3 mmol/day). For all 10 subjects, KHCO3 administration reduced urinary Ca excretion from control by -0.9 +/- 0.7 mmol/day, P less than 0.001. Net intestinal Ca absorption did not change detectably so that Ca balances became less negative by a +0.9 +/- 0.9 mmol/day; P = 0.01. KHCO3 administration was also accompanied by more positive PO4 and Mg balances. NaHCO3 administration had no significant effect on urinary Ca excretion or Ca balance. NaHCO3 and KHCO3 administration were accompanied by equivalently more positive Na or K balances, respectively and equivalently more negative acid balances (HCO3 retention). Neither NaHCO3 or KHCO3 altered fasting serum HCO3 concentrations, blood pH, serum 1,25-(OH)2-D or PTH concentrations. We conclude that KHCO3 promotes more positive Ca balances by either enhancing renal Ca retention or skeletal Ca retention or both.