Drinking Baking Soda for Vagal Nerve Stimulation?

 The easy to read article: -

Drinking baking soda could be an inexpensive, safe way to combat autoimmune disease

 The original paper:-

Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells

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:

https://www.drthrasher.org/macrophages

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. 

Macrophages and Inflammatory Mediators in Chemical Toxicity: A Battle of Forces

 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

Oral NaHCO3 Activates a SplenicAnti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells

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.

Increased blood pH but not performance with sodium bicarbonate supplementation in elite rugby union players.

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:-

https://www.ochec.com/2de646a5-4b92-4b42-becf-b2c39226e6d1

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 

Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men.

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.

Transcutaneous Vagal Nerve Stimulation - a Potential Cognitive Therapy?

 Sham device left and the real one on the right

In older posts there was quite a lot written about the vagal nerve and a method of stimulating it, called vagal nerve stimulation (VNS). VNS is already used by many thousands of people with epilepsy; more recently a much milder kind of stimulation has been developed to improve learning after a stroke.

This kind of therapy requires a 40 minute operation to attach the device inside the body. Even though it looks like VNS makes a dramatic improvement in rehabilitation following a stroke, I do not see children without epilepsy being fitted with internal VNS devices any time soon.

Traditionally VNS requires making a connection directly to the main vagus nerve, however the vagus nerve has many branches leading to it.

A German company Cerbomed has created a non-invasive, transcutaneous (through the skin) VNS device (tVNS) that stimulates the afferent auricular branch of the vagus nerve located in your ear.

“This device has received CE approval as indication that it complies with essential health and safety requirements. Thus, tVNS is safe and accompanied only by minor side effects such as slight pain, burning, tingling, or itching sensation under the electrodes.  

Given that the right vagal nerve has efferent fibers to the heart, tVNS is safe to be performed only in the left ear.”

There are several kinds of electric and magnetic stimulation already used in autism - Transcranial Magnetic Stimulation (TMS), transcranial direct current stimulation (tDCS) and ECT.

ECT was covered in this post:-

Electro Convulsive Therapy (ECT) in Autism

Manuel Casanova, neuropathologist and bilingual autism blogger is a fan of TMS

Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Event-Related Potential (ERP) Indices of Attention in Autism

Transcranial direct current stimulation (tDCS) is a form of neurostimulation that uses constant, low direct current (DC) delivered via electrodes on the head; it can be contrasted with cranial electrotherapy stimulation which generally uses alternating current (AC) the same way.

It was originally developed to help patients with brain injuries or psychiatric conditions like major depressive disorder.

Transcranial Direct Current Stimulation to the RightTemporoparietal Junction for Social Functioning in Autism Spectrum Disorder: A Case Report.

METHODS:

The authors present a case of an 18-year old patient with ASD treated successfully with tDCS; 1.5 mA of tDCS was applied once a day for 30 minutes for 8 consecutive days with the anode electrode over rTPJ (CP6 in the 10/10 electroencephalogram system) and the cathode electrode placed on the ipsilateral deltoid. Behavioral outcome was assessed using the Autism Treatment Evaluation Checklist prior to tDCS, after the final tDCS session, and at 2 months after tDCS. An additional, informal follow-up was also made 1 year after tDCS.

RESULTS:

Autism Treatment Evaluation Checklist showed substantial improvement in social functioning from baseline to post-tDCS, which was maintained at 2 months. The patient also reported lessened feelings of anger and frustration over social disappointments. Informal follow-up 1 year after stimulation indicates that the patient continues to maintain many improvements.

CONCLUSIONS:

Anodal tDCS to the rTPJ may represent an effective treatment for improving social functioning in ASD, with a larger clinical trial needed to validate this effect.

Transcutaneous Vagal Nerve Stimulation (tVNS) 

The new nerve stimulation therapy for stroke survivors

Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke Recovery

Conclusions—This study provides the first evidence that VNS paired with rehabilitative training after stroke (1) doubles long-lasting recovery on a complex task involving forelimb supination, (2) doubles recovery on a simple motor task that was not paired with VNS, and (3) enhances structural plasticity in motor networks.

Will non-invasive vagus nerve stimulation help improve upper limb function following stroke?   Efficacy of a Novel Transcutaneous Vagus Nerve Stimulation Therapy on Motor Recovery after Stroke

Scientific Explanation of VNS Paired Stimulation for Tinnitus and Stroke Rehabilitation

http://www.microtransponder.com/

http://www.microtransponder.com/en-gb/stroke/physicians/stroke-technology

Each time the vagus nerve is stimulated, it sends a signal up to the brain, which triggers the release of neurotransmitters (acetylcholine and norepinephrine)   broadly across the brain thus enabling neuroplasticity. In effect it is telling the brain to pay attention to the task at hand.

In someone having therapy after a stroke this might be learning to open a jar, but in autism it might be speech therapy.

The image below illustrates the therapy in action. While the patient is performing a rehabilitative exercise, the physical therapist pushes a button, which triggers the wireless transmitter to send a signal to the implanted device to deliver a small burst of electrical stimulation to the vagus nerve.

big clinical trial:-   www.vnsstroketrial.com/

Conclusion 

It does seem that using electricity in one way or another does have some therapeutic effect in some people with autism. The reason it may be effective in some people is not always entirely clear.

Personally, I like the idea of tVNS to potentially give a learning boost during 1:1 therapy to struggling learners with autism, just as VNS is being used in elderly people who have lost function in their limbs after a stroke and need to relearn how to control their muscles.

It appears that the amount of electricity used in stroke patients is much lower (one 60th) than in those with epilepsy. Perhaps it will be possible to develop a tVNS therapy that does cause any discomfort in the patient’s ear.  

Nobody is researching transcutaneous vagal nerve stimulation for improved learning in autism, given that some doctors at leading hospitals like Johns Hopkins do seem to like zapping people with autism, perhaps somebody should. There looks to be more science behind this than some other shock treatments, which do look quite crude, but do seem to help some people.  

Parkinson’s Disease and the Vagal Nerve

We saw in an earlier post that what goes on in the gut is communicated to the brain, bypassing the blood brain barrier, via the vagal nerve.  In that post it was mice who had their vagal nerve severed in the name of science.

Until recently a common therapy in humans with peptic ulcers was to severe the vagal nerve.  It turns out that these people are protected from developing Parkinson’s Disease. Interesting?

 Parkinson's disease may begin in the gut

Sensory Gating in Autism, Particularly Asperger's

Sensory gating is an issue in autism, schizophrenia and ADHD.   It is the neurological process of filtering out redundant or unnecessary stimuli in the brain; like the child who sits in his classroom and gets bothered by the noise of the clock on the wall.  He is unable to filter out and ignore this sound. He becomes preoccupied by the sound and cannot concentrate on his work.

There are also sometimes advantages to not filtering out environmental stimuli, because you would have more situational awareness and notice things that others miss.

An example of sensory gating is the fact that young children are not waken by smoke detectors that have high pitched siren, but are waken by a recorded human voice telling them there is a fire and to wake up.

There may be times when sensory overload in autism is not a case of too much volume from each of the senses, but rather too many inputs being processed by the brain, instead of some just being ignored.  It is more a case of information overload.

Note that this blog has already covered hypokalemic sensory overload in some depth, which is treatable.

Much is known about sensory gating because it has long been known to be a problem in schizophrenia.

An EEG (Electroencephalography) test measures your brain waves / neural oscillations. Many people with autism have EEGs, but mainly those in which epilepsy is a consideration.

In the world of the EEG, the P50 is an event occurring approximately 50 millisecond after the presentation of an auditory click.  The P50 response is used to measure sensory gating, or the reduced neurophysiological response to redundant stimuli.

Abnormal P50 suppression is a biomarker of schizophrenia, but is present in other disorders, including Asperger’s, post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI).

In more severe autism abnormal P50 suppression was found not to be present in one study.  This might be because cognition and the senses are dimmed by the excitatory-inhibitory imbalance.

More broadly, sensory gating is seen as an issue in wider autism and ADHD.

Correcting P50 gating

It is known that α7 nicotinic acetylcholine receptor (α7 nAChR) agonists can correct the impaired P50 gating. It is also known that people with schizophrenia have less expression of this receptor in their brains than typical people.

One short term such agonist is the nicotine released from smoking.  This likely contributes to why people with schizophrenia can be heavy smokers.  The effect is thought to last for about 30 minutes.

Clinical trials using Tropisetron, a drug that is a α7 nAChR agonist and used off-label to treat fibromyalgia, have shown that it can correct defective P50 gating and improve cognitive function in schizophrenia.

An alternative α7 nAChR agonist that is widely available is varenicline, a drug approved to help people stop smoking.

So you might expect varenicline to improve P50 gating and improve cognition. You might also expect it to help people with fibromyalgia and indeed some other people with chronic inflammation, as shown by elevated inflammatory cytokines.

You may recall that the α7 nAChR is the key to stimulating the vagus nerve and this should be beneficial to many people with inflammatory conditions (from arthritis to fibromyalgia).

Brief Report: Initial Trial of Alpha7-Nicotinic Receptor Stimulation in Two Adult Patients with Autism Spectrum Disorder

Abnormalities in CHRNA7, the alpha7-nicotinic receptor gene, have been reported in autism spectrum disorder. These genetic abnormalities potentially decrease the receptor’s expression and diminish its functional role. This double-blind, placebo-controlled crossover study in two adult patients investigated whether an investigational receptor-specific partial agonist drug would increase the inhibitory functions of the gene and thereby increase patients’ attention. An electrophysiological biomarker, P50 inhibition, verified the intended neurobiological effect of the agonist, and neuropsychological testing verified a primary cognitive effect. Both patients perceived increased attention in their self-ratings. Alpha7-nicotinic receptor agonists, currently the target of drug development in schizophrenia and Alzheimer Disease, may also have positive clinical effects in autism spectrum disorder.

α7-nicotinic acetylcholine receptor agonists for cognitive enhancement in schizophrenia

A role for H3 and HI histamine receptors

It has also been suggested that histamine plays a role in sensory gating via the H1 and H3 receptors.

It had also been thought H3 receptors could be targeted to improve cognition in schizophrenia, but that research really did not go anywhere.

Meclizine enhancement of sensorimotor gating in healthy male subjects with high startle responses and low prepulse inhibition.

Histamine H₁ receptor systems have been shown in animal studies to have important roles in the reversal of sensorimotor gating deficits, as measured by prepulse inhibition (PPI). H₁-antagonist treatment attenuates the PPI impairments caused by either blockade of NMDA glutamate receptors or facilitation of dopamine transmission. The current experiment brought the investigation of H₁ effects on sensorimotor gating to human studies. The effects of the histamine H₁ antagonist meclizine on the startle response and PPI were investigated in healthy male subjects with high baseline startle responses and low PPI levels. Meclizine was administered to participants (n=24) using a within-subjects design with each participant receiving 0, 12.5, and 25 mg of meclizine in a counterbalanced order. Startle response, PPI, heart rate response, galvanic skin response, and changes in self-report ratings of alertness levels and affective states (arousal and valence) were assessed. When compared with the control (placebo) condition, the two doses of meclizine analyzed (12.5 and 25 mg) produced significant increases in PPI without affecting the magnitude of the startle response or other physiological variables. Meclizine also caused a significant increase in overall self-reported arousal levels, which was not correlated with the observed increase in PPI. These results are in agreement with previous reports in the animal literature and suggest that H₁ antagonists may have beneficial effects in the treatment of subjects with compromised sensorimotor gating and enhanced motor responses to sensory stimuli.

Histamine and acetylcholine receptor involvement in sensorimotor gating: an autoradiography study

The aim of this study was to investigate an established rat model of decreased PPI induced by administration of the NMDA antagonist, dizocilpine and the reversal of this PPI impairment by the histaminergic H1-antagonist, pyrilamine. H1-antagonism is a potential mechanism of the therapeutic effects of the atypical antipsychotic, clozapine, which improves PPI following dizocilpine administration in rats as well as in patients with schizophrenia. In the present study we show that chronic pyrilamine administration prevents the PPI impairment induced by chronic dizocilpine administration, an effect that is correlated with a reduction in ligand-binding potential of H1 receptors in the anterior cingulate and an increase in nicotinic receptor α7 subunit binding in the insular cortex. In light of the functional anatomical connectivity of the anterior cingulate and insular cortex, both of which interact extensively with the core PPI network, our findings support the inclusion of both cortical areas in an expanded network capable of regulating sensorimotor gating.

Histamine H3 Receptor Regulates Sensorimotor Gating and Dopaminergic Signaling in the Striatum.

The brain histamine system has been implicated in regulation of sensorimotor gating deficits and in Gilles de la Tourette syndrome. Histamine also regulates alcohol reward and consumption via H3 receptor (H3R), possibly through an interaction with the brain dopaminergic system. Here, we identified the histaminergic mechanism of sensorimotor gating and the role of histamine H3R in the regulation of dopaminergic signaling. We found that H3R knockout mice displayed impaired prepulse inhibition (PPI), indicating deficiency in sensorimotor gating. Histamine H1 receptor knockout and histidine decarboxylase knockout mice had similar PPI as their controls. Dopaminergic drugs increased PPI of H3R knockout mice to the same level as in control mice, suggesting that changes in dopamine receptors might underlie deficient PPI response when H3R is lacking. Striatal dopamine D1 receptor mRNA level was lower, and D1 and D2 receptor-mediated activation of extracellular signal-regulated kinase 1/2 was absent in the striatum of H3R knockout mice, suggesting that H3R is essential for the dopamine receptor-mediated signaling. In conclusion, these findings demonstrate that H3R is an important regulator of sensorimotor gating, and the lack of H3R significantly modifies striatal dopaminergic signaling. These data support the usefulness of H3R ligands in neuropsychiatric disorders with preattentional deficits and disturbances in dopaminergic signaling.

Conclusion

Other than nicotine, varenicline would seem a good potential therapy for sensory gating.  There are α7-nicotinic acetylcholine receptor agonists in development.

There are many H1 histamine antagonists.  Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H₁ receptors. Centrally acting H1 antihistamines are sedating.

H3 antagonists have stimulant and nootropic effects. Betahistine is an approved drug in this class, there are many research drugs.

The role of histamine dysfunction in sensory and cognitive deficits in schizophrenia

The aim of this study is to investigate the role of the neurotransmitter histamine in sensory and cognitive deficits as they often occur in schizophrenia patients (e.g. hearing voices, planning and memory problems). The ideal location to conduct the study and to obtain a unique learning experience is at the Institute of Psychiatry, London, United Kingdom, where staff comprises of leading experts in the field of schizophrenia and Magnetic Resonance Imaging of pharmacological effects. Current pharmacological treatment of psychotic symptoms including sensory and cognitive deficits remains partially unsuccessful due to side effects and treatment resistance. The neurotransmitter histamine seems to be a very promising target for new treatments. It has been found that histamine neurotransmission is altered in brains of schizophrenics, which may contribute to both the hallucinatory and cognitive symptoms. However, this specific role of histamine has not been investigated before. I will assess the effects of increased histaminergic activity, by administration of betahistine to healthy volunteers, on performance (sensory gating, executive functioning or planning and memory) and associated brain activity using fMRI. Altered performance and brain activity would support the importance of histamine in schizophrenia and would provide a research model and target for new treatments.

Other interesting Probiotic Bacteria for Cholesterol, Osteoporosis, Diabetes, Eczema, Asthma, Cancer and perhaps some Autism

  

In the next 30 to 50 years I think many common diseases will be, in part, treated by bacteria.  There is already a great deal of research to show that gut bacteria play a key role in both some diseases and the effectiveness of some therapies.

I was surprised to read that the effectiveness of some common existing cancer drugs appears to depend on the presence, or not, of specific gut bacteria.

Many gut bacteria have very specific, but different, effects on the immune system.  There may be no one-size-fits-all options and it is not a case of good bacteria and bad bacteria.  Too much of some “good” bacteria and they becomes “bad” bacteria.

Taking a pragmatic approach you can look at the effects of widely available probiotic bacteria and see if any might have a beneficial effect on a specific person’s autism.

We already saw in the trials that people made following Alli from Switzerland’s revelation about the two L.reuteri bacteria found in Biogaia Gastrus, that what is good for one person might not be effective in the next person.

In my case one of the L.reuteri bacteria in Biogaia Gastrus has a profound positive effect on allergy, and hence autism, while the second bacteria has negative behavioral effects.  Fortunately, the L.reuteri protectis bacteria in Biogaia Gastrus can be purchased separately.

Not surprisingly, companies are patenting the bacteria with research-proven therapeutic effects.  Many supplement companies are using the non-patented bacteria because they are cheaper.  Very often they do not specify exactly which sub-type of bacteria they use and you have no means of knowing whether they change the bacteria over time depending on pricing and availability.

Nonetheless if you skim through the probiotic bacteria research and anecdotal evidence there are some interesting options.

 

First a quick recap

So far in this blog we have seen some particularly interesting individual probiotic bacteria:-

Miyairi 588 from Japan produces butyric acid in the gut.  Butyric acid has been shown to have several interesting effects.  It improves immune health and for this reason is included in animal feed.  It has been shown to improve the integrity of gut to avoid “leaky gut”.  It is an HDAC inhibitor which means it may well have epigenetic effects.  It is an alternative to using butyrate supplements.

 Lactobacillus reuteri 17938 (Lactobacillus reuteri Protectis)

This bacteria is the one we are using and it has potent effects on my son’s summertime allergy that makes his autism much worse.

Lactobacillus reuteri ATCC PTA 6475

This is a potent anti-inflammatory bacteria, but its mode of action does not agree with my son, but it seems to do great things for many others.

Viviomixx and VSL#3

We saw that many people with IBS/IBD and some with autism find these two combination bacteria helpful.  Being a mixture of bacteria means that it may be only certain ingredients that have a helpful effect in a specific person with autism.

Many people with types of IBD/IBS do seem to respond well to the combined bacteria found in Viviomixx and VSL#3.

Some other interesting, commercially available, bacteria

I came across several interesting products. 

Lactobacillus reuteri NCIMB 30242

This bacteria is very well researched and has effects on some of comorbidities that effect some people with autism, such as vitamin D metabolism and calcium homeostasis.

As is often the case the benefits mainly relate to the immune system.  This particular bacteria reduces C-reactive protein (CRP) which is a commonly used marked for inflammation.  It reduces “bad” cholesterol and it has an odd effect on vitamin D making it interesting for people with reduced bone density.

I have no idea if it will help some people with autism, but it is very easy to find out since this patented bacteria is available in several products, targeted at your heart, GI or bones but also lightening your wallet.

Given how quick the L.reuteri protectis showed effect (1 day) I only intend to trial NCIMB 30242 for a few days.

Lactobacillus reuteri NCIMB 30242 research

L. reuteri NCIMB 30242: A Probiotic with Benefits

 Objectives

 The objective of this study was to evaluate the effects of probiotic bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 on cholesterol lowering, mechanism of action and gastrointestinal (GI) symptomatology in hypercholesterolemic adults.

Methods 127 subjects consumed either L. reuteri NCIMB 30242 or placebo capsules over a 9-week intervention period in a randomized controlled trial.

Results L. reuteri NCIMB 30242 capsules reduced LDL-cholesterol by 11.6% (P=0.001), total cholesterol by 9.1%, 

Conclusions L. reuteri NCIMB 30242 capsules should be considered as an adjunctive therapy for hypercholesterolemia and may be useful for promoting GI health.

  

Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D: a post hoc analysis of a randomized controlled trial.

L. reuteri NCIMB 30242 increased serum 25-hydroxyvitamin D by 14.9 nmol/L, or 25.5%, over the intervention period, which was a significant mean change relative to placebo of 17.1 nmol/L, or 22.4%, respectively (P = .003).

CONCLUSIONS:

To our knowledge, this is the first report of increased circulating 25-hydroxyvitamin D in response to oral probiotic supplementation.

  

Building healthy bones takes guts

Probioticboosts bone density in mice, could point way to new, natural treatments for osteoporosis

  

"We know that inflammation in the gut can cause bone loss, though it's unclear exactly why," said lead author Laura McCabe, a professor in MSU's departments of Physiology and Radiology. "The neat thing we found is that a probiotic can enhance bone density."

In the study, the male mice showed a significant increase in bone density after four weeks of treatment. There was no such effect when the researchers repeated the experiment with female mice, an anomaly they're now investigating.

Lactobacillus Reuteri NCIMB 30350

One reader of this blog is already a fan of Lactobacillus Reuteri NCIMB 30350 which comes from BioAmicus in Canada.

BioAmicus have had feedback from other customers who tried it having read the press reports on Lactobacillus Reuteri and autism.

 They told me:-

“The parents who have seen improvement with BioAmicus Reuteri note eye contact, social activity, language use, as well as improved instruction comprehension.”

They plan to make their own autism clinical trial.

                     https://bioamicus.com/autism-research/

Lactobacillus Johnsonii NCIMB 30351

The next interesting bacteria I came across is Lactobacillus Johnsonii.  There numerous strains.

This bacteria has been shown to be behind why children who live in a house with pet dog are protected from asthma.  Numerous studies like the auto immune disease asthma with increased incidence of autism.

The bacteria is protective against development of another auto immune disease, Type 1 diabetes.

Lactobacillus Johnsonii appears to mediate the effectiveness of some common cancer drugs.

BioAmicus have a Lactobacillus Johnsonii bacteria called NCIMB 30351 usually given to babies.

  

As some readers have already highlighted Lactobacillus bacteria can be used to make all kinds of yoghurt, kefir etc.  So you can grow your own at home to keep the cost down.

Lactobacillus johnsonii research

House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection

Early-life exposure to dogs is protective against allergic disease development, and dog ownership is associated with a distinct milieu of house dust microbial exposures. Here, we show that mice exposed to dog-associated house dust are protected against airway allergen challenge. These animals exhibit reduced Th2 cytokine production, fewer activated T cells, and a distinct gut microbiome composition, highly enriched for Lactobacillus johnsonii, which itself can confer airway protection when orally supplemented as a single species. This study supports the possibility that host–environment interactions that govern allergic or infectious airway disease may be mediated, at least in part, by the impact of environmental exposures on the gastrointestinal microbiome composition and, by extension, its impact on the host immune response.

Research Shows How Household Dogs Protect Against Asthma, Infection

UCLA research suggests that gut bacteria could help prevent cancer

  

The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide

 Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of “pathogenic” T helper 17 (pT_H17) cells and memory T_H1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT_H17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT_H17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

Lactobacillus Johnsonii N6.2 Mitigates the Development of Type 1 Diabetes in BB-DP Rat

Inhibition of Type 1 Diabetes Correlated to a Lactobacillus johnsonii N6.2-Mediated Th17 Bias

Although it is known that resident gut flora contribute to immune system function and homeostasis, their role in the progression of the autoimmune disease type 1 diabetes (T1D) is poorly understood. Comparison of stool samples isolated from Bio-Breeding rats, a classic model of T1D, shows that distinct bacterial populations reside in spontaneous Bio-Breeding diabetes-prone (BBDP) and Bio-Breeding diabetes-resistant animals. We have previously shown that the oral transfer of Lactobacillus johnsonii strain N6.2 (LjN6.2) from Bio-Breeding diabetes-resistant to BBDP rodents conferred T1D resistance to BBDP rodents, whereas Lactobacillus reuteri strain TD1 did not. In this study, we show that diabetes resistance in LjN6.2-fed BBDP rodents was correlated to a Th17 cell bias within the mesenteric lymph nodes. The Th17 bias was not observed in the non-gut–draining axillary lymph nodes, suggesting that the Th17 bias was because of immune system interactions with LjN6.2 within the mesenteric lymph node. LjN6.2 interactions with the immune system were observed in the spleens of diabetes-resistant, LjN6.2-fed BBDP rats, as they also possessed a Th17 bias in comparison with control or Lactobacillus reuteri strain TD1–fed rats. Using C57BL/6 mouse in vitro assays, we show that LjN6.2 directly mediated enhanced Th17 differentiation of lymphocytes in the presence of TCR stimulation, which required APCs. Finally, we show that footpad vaccination of NOD mice with LjN6.2-pulsed dendritic cells was sufficient to mediate a Th17 bias in vivo. Together, these data suggest an interesting paradigm whereby T1D induction can be circumvented by gut flora-mediated Th17 differentiation.

The effect of Lactobacillus johnsonii Ncc533 (La1) on the balance of Th1/Th2 cells in BALB/c mice

  

 Lactobacillus rhamnosus GG

  
This bacteria has numerous scientifically researched beneficial effects. Most recently it was shown to affect the expression of GABA receptors.  For some people with autism this might be beneficial. In particular it may reduce anxiety, since this was the effect noted in mouse research.

Lactobacillus rhamnosus GG (ATCC 53103) is a strain of L. rhamnosus that was isolated in 1983 from the intestinal tract of a healthy human being; filed for patent on 17 April 1985, by Sherwood Gorbach and Barry Goldin, and the 'GG' derives from the first letters of their surnames. 

The patent refers to a strain of "L. acidophilus GG" with American Type Culture Collection (ATCC) accession number 53103; later reclassified as a strain of L. rhamnosus. The patent claims the L. rhamnosus GG (ATCC 53103) strain is acid- and bile-stable, has a great avidity for human intestinal mucosal cells, and produces lactic acid. Since the discovery of the L. rhamnosus GG (ATCC 53103) strain, it has been studied extensively on its various health benefits and currently L. rhamnosus GG (ATCC 53103) strain is the world's most studied probiotic bacterium with more than 800 scientific studies.

The genome sequence of Lactobacillus rhamnosus GG (ATCC 53103) has been decoded.

Medical research and use

While Lactobacillus rhamnosus GG (ATCC 53103) is able to survive the acid and bile of the stomach and intestine, is claimed to colonize the digestive tract, and to balance intestinal microflora, evidence suggests that Lactobacillus rhamnosus is likely a transient inhabitant, and not autochthonous. Regardless, it is considered a probiotic useful for treatment of various maladies, as it works on many levels. Most of the molecular mechanisms are not known, however.

Peanut allergy

Research is showing that L. rhamnosus as a probiotic could stop allergic reactions to peanuts in 80% of children.

Diarrhea

Lactobacillus rhamnosus GG has been shown beneficial in the prevention of rotavirus diarrhea in children. The prevention and treatment of various types of diarrhea has been shown both in children and in adults.

Respiratory tract infections

L. rhamnosus GG may reduce the risk of obtaining respiratory tract infections in children that attend daycare.

Atopic dermatitis, eczema

Lactobacillus rhamnosus GG also has shown potential in treatment and primary prevention of atopic dermatitis, but the results of intervention trials have been mixed. A clinical trial with seven-year follow-up shows L. rhamnosus GG is useful in the prevention of atopic dermatitis in children at high risk of allergy.

Urogenital tract

The clinical health effects of L. rhamnosus GG have been widely studied. Both L. rhamnosus GG and L. rhamnosus GR-1 appear to protect the urogenital tract by excreting biosurfactants to inhibit the adhesion of vaginal and urinary pathogens.

Intestinal tract permeability

L. rhamnosus has been found to reduce intestinal permeability in children who suffer from irritable bowel syndrome, and it also has been found to counter alcohol-related intestinal permeability.

Gastrointestinal carriage of VRE

In 2005, L. rhamnosus GG was first used successfully to treat gastrointestinal carriage of vancomycin-resistant Enterococcus (VRE) in renal patients.

Anxiety

Research published in the Proceedings of the National Academy of Sciences on August 29, 2011 reported this bacterium may have an effect on GABA neurotransmitter receptors. Mice who were fed L. rhamnosus JB-1 had less anxiety and had different levels of a brain-chemical sensor and stress hormones.

This paper was mentioned previously in this blog

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA_B1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA_Aα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABA_Aα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.

Weight loss

Research published in the British Journal of Nutrition in 2013 suggests that Lactobacillus rhamnosus CGMCC 1.3724 may increase weight loss in women who are dieting. The research was initiated after several studies showed that the gut bacteria in obese individuals differs significantly from those in thin people. Women in the study lost nearly twice the weight that the placebo group lost. No difference was observed in men, however.

Risks

The use of L. rhamnosus GG for probiotic therapy has been linked with very rare cases of sepsis in certain risk groups, primarily those with a weakened immune system and infants. Ingestion of L. rhamnosus GG is, nevertheless, considered to be safe, and data from Finland show a significant growth in the consumption of L. rhamnosus GG at the population level has not led to an increase in the number of Lactobacillus bacteraemia cases.

Probiotic Lactobacillus Probiotic rhamnosus downregulates FCER1 and HRH4 expressionin human mast cells

Abstract

AIM: To investigate the effects of four probiotic bacteria and their combination on human mast cell gene expression using microarray analysis.

METHODS: Human peripheral-blood-derived mast cells were stimulated with Lactobacillus rhamnosus (L. rhamnosus) GG (LGG^®), L. rhamnosus Lc705 (Lc705), Propionibacterium freudenreichii ssp. shermanii JS (PJS) and Bifidobacterium animalis ssp. lactis Bb12 (Bb12) and their combination for 3 or 24 h, and were subjected to global microarray analysis using an Affymetrix GeneChip^® Human Genome U133 Plus 2.0 Array. The gene expression differences between unstimulated and bacteria-stimulated samples were further analyzed with GOrilla Gene Enrichment Analysis and Visualization Tool and MeV Multiexperiment Viewer-tool.

RESULTS: LGG and Lc705 were observed to suppress genes that encoded allergy-related high-affinity IgE receptor subunits α and γ (FCER1A and FCER1G, respectively) and histamine H4 receptor. LGG, Lc705 and the combination of four probiotics had the strongest effect on the expression of genes involved in mast cell immune system regulation, and on several genes that encoded proteins with a pro-inflammatory impact, such as interleukin (IL)-8 and tumour necrosis factor alpha. Also genes that encoded proteins with anti-inflammatory functions, such as IL-10, were upregulated.

CONCLUSION: Certain probiotic bacteria might diminish mast cell allergy-related activation by downregulation of the expression of high-affinity IgE and histamine receptor genes, and by inducing a pro-inflammatory response.

Bifidobacterium Infantis 35624 

Bifidobacterium infantis 35624  is marketed in the US by Proctor & Gamble, while in Europe it is sold by the Irish developer.

It is well researched and does have effects beyond the gut.

Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut

Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear. In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding. These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.

The research highlighted by Proctor & Gamble is here:-

http://www.bifantis.com/probiotic-scientific-data.php

The product is sold as Alflorex in Europe and Align in the US.

               http://www.alimentaryhealth.ie/products/Alflorex

Conclusion

One big issue with all probiotics is just how potent they are when you actually consume them, rather than when they are manufactured.

Most people are taking probiotics for very general reasons, but people with IBS/IBD are a group who have very specific problems.  VSL#3 and Viviomixx do seem to be the probiotics of choice among those with IBS/IBD.

For allergy and atopic dermatitis some people clearly benefit from specific probiotics such as Bifidobacterium lactis BB-12 and Lactobacillus GG, but not all people respond.

Lowering cholesterol by probiotic is very easy to verify, so I presume it really must work in some cases.

Generally reducing colic, reflux, gas etc. in babies is a claim made for numerous probiotics.

You could spend a vast amount of money on probiotics for autism and it really is only worth using one(s) that have a genuine impact.

It would be useful to collect some data on what dosage is required when somebody actually does respond behaviourally to a probiotic.  Thanks to Alli and other readers I think we have the data on Biogaia products.

So far only one reader has given feedback on Lactobacillus Reuteri NCIMB 30350 (Bioamicus), but it was positive. The people at BioAmicus in Canada are very interested to know if their products are effective in some autism.

There are many people in the US using Culturelle for kids with autism, but I did not see any rave reviews.  Probably it is used for GI problems rather than to improve autism itself.

It does depend a lot where you live, how easy it is to access specific probiotics at a reasonable price.  Some are much cheaper in the US and some cheaper in Europe.

My current list of potentially interesting probiotics is:-

I really never expected to be writing about the merits of probiotics. It was a big surprise to learn that Miyiari 588 is put in animal feed to improve immune health via increasing the SCFA (short chained fatty acid) butyric acid.  Butyric acid is relevant to autism.  It was a bigger surprise to see L.reuteri Protectis reduce my son’s troublesome pollen allergy and changed the colour of his nose.

It is worthwhile doing some experimentation to see what, if anything, actually is helpful.

There are sound reasons why some people with autism may respond to one of the above bacteria.  As of now though, Biogaia is the probiotic of choice to try first, since many people with autism respond well.

All positive and negative feedback on these, or any other probiotic bacteria is very welcome.