Showing posts with label Vagus nerve. Show all posts
Showing posts with label Vagus nerve. Show all posts

Friday 26 April 2019

The Autonomic Nervous System (ANS), Heart Rate Variability (HRV), Performance Anxiety, Propranolol, Vagus Nerve Stimulation and Autism

Performance anxiety symptoms may include:
·       Racing pulse and rapid breathing.

·       Dry mouth and tight throat.

·       Trembling hands, lips, and voice.

·       Sweaty and cold hands.

·       Nausea 

·       Vision changes.

Today’s post started out to be all about Propranolol, a very old and widely prescribed drug that lowers your blood pressure, but does other interesting things as well. It is used to treat several psychiatric disorders and has been widely trialled in autism. As I started researching I decided to broaden the post to bring in Heart Rate Variability (HRV), which one reader of this blog suggested as a useful measure of the effect of supplements.   HRV is actually a good indicator of a dysfunction in the Autonomic Nervous System (ANS). 

The Autonomic Nervous System (ANS) is a control system that acts largely unconsciously and regulates bodily functions such as the heart rate, digestion, respiratory rate, pupillary response and urination.
Within the brain, the autonomic nervous system is regulated by the hypothalamus. Autonomic functions include control of respiration, cardiac regulation, vasomotor activity (actions upon a blood vessel which alter its diameter) and certain reflex actions such as coughing, sneezing, swallowing and vomiting.
Dysfunctions in the Autonomic Nervous System (ANS) are known to be a common feature of autism.  Propranolol is known to affect the Autonomic Nervous System (ANS) and has been shown in numerous trials and case studies to improve some cases of autism.
Performance anxiety is a well-known off-label use of Propranolol.
Vagus Nerve Stimulation (VNS) is known to affect the Autonomic Nervous System (ANS) and is sometimes used to treat performance anxiety.

Vagus nerve stimulation (VNS) using an implanted device can have profound benefits in severe epilepsy. Less invasive VNS can be achieved transcutaneously and in particular via a branch of the vagus nerve that extends to your ear.
The vagus nerve has many roles including sending inflammatory signalling from the gut to the brain. We saw how this was proved, at least in mice, by severing the vagus nerve. Stimulating the vagus nerve can have significant anti-inflammatory effects, which is why it is being developed to treat a wide range of conditions ranging from arthritis to COPD (severe asthma).

We also saw in a post last year that drinking sodium/potassium bicarbonate has an effect that is very similar to VNS, in that it tamps down your immune system in a very similar way.

The Propranalol Autism Research
Fortunately, in 2018 a review of all Propranolol-related autism research was published. I found this out after having started to trawl through the old research.  The issue of Heart Rate Variability (HRV) as potential marker for propranolol responders that I focused in on, was also picked up in the review paper.

We can start with review paper, which happens to be from England, which still has not fully recovered from the Wakefield saga.  There is a real stigma about treating autism, better call it encephalopathy and treat that!

To date, there is no single medication prescribed to alleviate all the core symptoms of Autism Spectrum Disorder (ASD; National Institute of Health and Care Excellence, 2016). Both serotonin reuptake inhibitors and drugs for psychosis possess therapeutic drawbacks when managing anxiety and aggression in ASD. This review sought to appraise the use of propranolol as a pharmacological alternative when managing emotional, behavioural and autonomic dysregulation (EBAD) and other symptoms.
This review indicates that propranolol holds promise for EBAD and cognitive performance in ASD. Given the lack of good quality clinical trials, randomised controlled trials are warranted to explore the efficacy of propranolol in managing EBAD in ASD.

From the 16 articles identified, propranolol dosages ranged from 7.5 mg to 360 mg per day across a range of patients. All studies had a range of outcome measures for those diagnosed with ASD, including a focus on cognitive enhancement, management of social behaviours, EBAD, SIBs, and aggression.

Summary of evidence

Across multiple domains, propranolol had significant benefits in the treatment of adults and children diagnosed with ASD. Propranolol improved cognitive performance, with individuals with ASD demonstrating an improvement in verbal problem solving (Beversdorf et al., 2008; Zamzow et al., 2017), semantic processing (Beversdorf et al., 2011) and working memory (Bodner et al., 2012). No changes in cognitive performance for individuals without ASD were reported (Beversdorf et al., 2008, 2011). Additionally, propranolol exhibited greater functional connectivity in individuals with ASD (Hegarty et al., 2017; Narayanan et al., 2010). Not only does this provide evidence for the ability of propranolol to improve functional connectivity in those with ASD, but also that central and peripheral blockade is more effective than just peripheral blockade as seen by nadolol (Hegarty et al., 2017). It is important to note that a non-significant difference for functional connectivity between placebo and propranolol conditions can be attributed to other hemodynamic factors, such as differences in blood pressure, confounding the effects on blood-oxygen-level-dependent responses during fMRI sessions (Narayanan et al., 2010). Moreover, propranolol decreased functional connectivity in various subnetworks where high baseline functional connectivity was observed. Conversely, for those with low baseline functional connectivity, functional connectivity in these subnetworks increased after the introduction of propranolol, irrespective of diagnostic group (Hegarty et al., 2017). These differences suggest that propranolol, and other beta-adrenergic antagonists may have a greater role in maintaining appropriate patterns of functional connectivity, allowing for more efficient integration of functional networks (Hegarty et al., 2017). These findings also highlight the potential for propranolol to support cognitive processing. Indeed, by modulating noradrenaline, greater associative processing and integration of subnetworks may be achieved. Subsequently, potential improvements in attention-shifting, sensory processing, language communication, and the processing of social information could be observed in those with ASD (Hegarty et al., 2017). Furthermore, propranolol reduced mouth fixation, improving facial scanning at a global level (Zamzow et al., 2014). Although, non-significant findings were reported when investigating the efficacy of single-dose propranolol treatment for eye contact, this may be attributable to the sample used. The majority of subjects fulfilling diagnostic criteria for ASD were high functioning, suggesting that scores for eye contact may have already been at a ceiling prior to the administration of propranolol. Therefore, none or only marginal improvements would be attained from post administration of propranolol leading to non-significant results when compared with controls. Moreover, non-verbal communication improvements (Zamzow et al., 2016) and reductions in hypersexual behaviours (Agrawal, 2014) were also observed. These improvements were reported in studies using a 40 mg dose of propranolol, with just one study utilising a low dose of 20 mg (Agrawal, 2014). However, it may be noteworthy to consider that for this case, the hypersexual behaviours did not decrease while the patient was alone, but the patient was able to manage behaviours more appropriately in the presence of others. This may indicate an improved ability to understand and interpret social contexts, rather than a reduction in hypersexual behaviours. Indeed, social cues and social situations are a challenge for those with ASD, and these findings highlight potential clinical implications for propranolol. In light of this, both studies by Sagar-Ouriaghli et al. (2017) and Santosh et al. (2017) highlight again that on average, a 40 mg dose is suitable for children and adolescents in managing symptoms associated with ASD and EBAD. Furthermore, Santosh et al. (2017) and Zamzow et al. (2017) provide supporting evidence for the use of wearable technologies in measuring biomarkers such as HRV and skin conductance in order to identify treatment responders and monitoring the impact of propranolol on therapeutic outcomes. Alongside these benefits, propranolol significantly helped manage SIBs and aggressive outbursts in those with ASD (Knabe and Bovier, 1992; Lyskowski et al., 2009; Ratey et al., 1987). Two cases reported no significant improvement when using propranolol (Connor, 1994; Luiselli et al., 2000). One case was required to change propranolol due to hypotension and bradycardia despite a decreasing trend in aggressive behaviours (Luiselli et al., 2000). Across these cases, dosing ranged from 7.5 mg–360 mg, indicating a higher dose may be required for SIBs and aggression, in comparison with cognitive performance (20 mg–40 mg). In summary, these results and a subsequent overview by Fleminger et al. (2006) conclude that β-blockers have the best evidence for the management of such symptoms and that propranolol improves impulse control and subsequent violence associated with brain dysfunction of diverse aetiologies.

You can read the original 16 studies referred to if you are seriously interested in Propranolol. I have just highlighted some I found interesting.  It is interesting that beneficial effects are reported across the spectrum from severe autism to Asperger’s. 

People with intellectual disability often exhibit various behavioral problems, which are referred to as “challenging behaviors.” Aggression is among the commonest of these, affecting about 7% of this population. The management of aggression in these patients involves both behavior therapy and medications. Various medications, such as lithium, anticonvulsants, and antipsychotics, have been used, but their evidence base is limited and recent research suggests that antipsychotics, in particular, should not be routinely used
Propranolol is a centrally acting β-adrenergic antagonist used in a variety of medical conditions. It has also been used to manage aggression in various neuropsychiatric conditions, including organic brain syndromes, schizophrenia, dementia, and intellectual disability. Doses used in these studies have been as high as 520 mg/d, but some authors have reported benefits at much lower doses. The following is the case of a young man with intellectual disability, epilepsy, and severe aggression who responded remarkably to low-dose propranolol.
Case report. Mr A, a 20-year-old man diagnosed as having moderate intellectual disability and generalized epilepsy, presented to our clinic with severe aggression, both verbal and physical, occurring with little or no provocation over the past 3 years. These episodes would last up to several hours and often led to food refusal. Before this, he could attend to his personal needs, helped his mother in household tasks, and could communicate in short sentences despite an articulation defect. However, after the onset of his aggression, it was difficult to engage him in any activities, including basic self-care. There was no evidence of a mood disorder or psychosis or of seizures either preceding or following the episodes of aggression. He was seizure-free for the past 4 years on carbamazepine 1,000 mg/d and diazepam 10 mg/d, and he had never exhibited postictal aggression in the past. He had already received trials of olanzapine (up to 15 mg/d for 6 weeks) and chlorpromazine (up to 400 mg/d for 3 months) without significant improvement and was currently on olanzapine 10 mg/d and chlorpromazine 300 mg/d in addition to his medications for epilepsy.

As his mother reported features of autonomic arousal—such as increased perspiration, motor agitation, and rapid breathing—during each episode, he was given a trial of propranolol, starting at 20 mg/d and increased by 20 mg every week. At 40 mg/d, there was a significant reduction in his aggression, and his food intake was better. On further increasing the dose to 60 mg/d, his mother reported that he was essentially “normal,” with no significant episodes of aggression. Over the next year, olanzapine and chlorpromazine were tapered and stopped, and he remained stable. He has been well on carbamazepine 1,000 mg/d, propranolol 60 mg/d, and diazepam 10 mg/d for the past 3 months with no recurrence of either seizures or aggression, and it is now possible to engage him in household tasks and speech therapy.
The management of aggression in the intellectually disabled is a clinical challenge. The best evidence suggests that antipsychotics are of limited use, and the evidence for other medications is even more limited. Behavioral management is valuable, but may not be feasible in a very violent or uncooperative patient, and pharmacotherapy may be required initially in such cases.
Propranolol is effective in reducing aggression in a variety of neurologic and psychiatric conditions. Its exact mechanism of action is unknown, but may involve central β-adrenergic blockade, peripheral effects on the sympathetic nervous system, or serotonergic blockade. It may be effective not only in aggression, but also in the self-injurious behavior commonly seen in the intellectually disabled. Recent evidence suggests that it may improve some aspects of learning in patients with autism. Given these properties, and the uncertainties surrounding other treatment options, low-dose propranolol may be a valuable treatment option in the management of aggression in intellectually disabled adults, even if they do not respond to other drugs.

Amelioration of Aggression and Echolalia With Propranolol in Autism Spectrum Disorder


Although the autonomic hyperactivity hypothesis of aggression in ASD partially explains the behavior of our patient, aggression likely stems from multiple sources beyond just peripheral autonomic arousal. The rapid improvement with propranolol at a fairly low dose suggests that a subpopulation of patients may benefit from non-selective beta blockers. As beta blockers have hemodynamic side effects that include hypotension and bradycardia, clinicians should record baseline vitals and monitor for orthostasis, dizziness, and syncope. Overall, beta blockers may serve as an important therapy for aggression but should not replace a multimodal interventional plan that encompasses pharmacology, psychotherapy, and social support. It will be beneficial to validate the utility of propranolol and other beta blockers for ASD in future randomized controlled trials.
·       Though autism spectrum disorder (ASD) is primarily a disorder of language and social functioning, there may also be significant autonomic dysfunction that could contribute to aggression and impulsivity often seen in the disorder.
·       Beta-adrenergic blocking agents have been shown to reduce aggression in patients with traumatic brain injury and adult-onset neuropsychiatric disorders, but evidence is still limited in patients with ASD.
·       The non-selective beta-blockers propranolol and nadolol may significantly alleviate aggression, echolalia, and vital sign derangements in autistic patients; it is unknown whether β1-selective antagonists would have similar effects.

Here we have the effect on high functioning autism:-


Autism is characterized by repetitive behaviors and impaired socialization and communication. Preliminary evidence showed possible language benefits in autism from the β-adrenergic antagonist propranolol. Earlier studies in other populations suggested propranolol might benefit performance on tasks involving a search of semantic and associative networks under certain conditions. Therefore, we wished to determine whether this benefit of propranolol includes an effect on semantic fluency in autism.


A sample of 14 high-functioning adolescent and adult participants with autism and 14 matched controls were given letter and category word fluency tasks on 2 separate testing sessions; 1 test was given 60 minutes after the administration of 40 mg propranolol orally, and 1 test was given after placebo, administered in a double-blinded, counterbalanced manner.


Participants with autism were significantly impaired compared with controls on both fluency tasks. Propranolol significantly improved performance on category fluency, but not letter fluency among autism participants. No drug effect was observed among controls. Expected drug effects on heart rate and blood pressure were observed in both the groups.


Results are consistent with a selective beneficial effect of propranolol on flexibility of access to semantic and associative networks in autism, with no observed effect on phonological networks. Further study will be necessary to understand potential clinical implications of this finding.

This paper is interesting because it looks at how you can identify people who are likely to respond to Propranolol:-

Autism spectrum disorders are a group of developmental disorders, which display significant heterogeneity of symptoms. Besides the core symptoms, various comorbidities are common for individuals with autism. A growing body of evidence suggests dysfunction of autonomic nervous system within the ASD population. The detection of autonomic abnormalities could help in more personalized approach, which takes into account individual etiologic differences. It has also been suggested that interventions focused on autonomic function could possibly be beneficial for treatment of aggression, anxiety, as well as the core symptoms of autism.
Detection of autonomic alterations in autism spectrum disorders

Invasive methods 
The measurement of circulating catecholamines belongs to most common methods of assessment of sympathetic nervous system function (SNS) (Zygmunt & Stanczyk 2010). Activity of the SNS can be assessed using the measurement of the plasma or urine concentration of norepinephrine, or its metabolites. Measurement of catecholamines provides useful information about the activity of SNS, however, they are determined by location of vessel used for blood collection and therefore do not reflect the whole amount of neurotransmitter secreted from axon terminal (Sinski et al 2006). Acetylcholine, neurotransmitter released by postganglionic fibers of the parasympathetic system, is very quickly inactivated by acetylcholinesterase, so its plasma levels cannot be used as a marker of parasympathetic nervous system activity (McCorry 2007). Interestingly, plasma norepinephrine concentrations have been reported to be elevated in autism (Launay et al 1987). However, blood and urine samples acquisition represent extremely stressful stimuli for children with autism spectrum disorders and thus pose a challenge for researchers in obtaining such samples from both ethical and methodological reasons. Therefore, various non-invasive methods of ANS activity detection have been developed. 
Non-invasive methods 
To assess autonomic nervous system activity, various non-invasive methods are used. For example, measurement of sympathetic skin response is used frequently (Claus & Schondorf 1999, Kucera et al 2004). This method is based on determination of the alterations in skin electrical resistance in response to activation of sweat glands which are stimulated by impulses conducted by cholinergic postganglionic sympathetic fibers. However, it is important to note, that in general, skin conductance level are not stable and therefore it is difficult to define baseline values and there are large intra- and inter-individual differences (Boucsein et al 2012). Another widely used method has become pupillometry, biomarker of LC-NE system. Several studies found both dysregulated tonic pupil responses to various stimuli (e.g. Anderson et al 2006, Martineau et al 2011) and greater skin conductance level (Prince et al 2016) in children with ASD. One of the most reliable methods for measurement of ANS activity, namely cardiac autonomic responses, has become heart rate variability (HRV). HRV refers to beat-to-beat variations of the heart rate that is determined by autonomic nervous system. In resting conditions, the variability of beat-to-beat intervals remains large and becomes more regular when influenced by stressful environmental factors (Task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology 1996). Because of the fast degradation of acetylcholine by acetylcholinesterase, the influence of parasympathetic activation is quick and thus accounts for fast changes in heart rate. Sympathetic influence changes more slowly, its effect is observable as a change in heart rate after longer period, and thus is responsible for slower oscillations. HRV has been found to be decreased in autism spectrum disorders in number of studies (Daluwatte et al 2013, Ming et al 2005). These data

Interventions affecting vagal activity for adjuvant treatment of children with ASD 

In the light of above mentioned findings, several new treatment options are now being explored. Vagus nerve stimulation, which involves surgical implantation of electrodes around cervical portion of the vagus nerve, was found to increase HRV. Study of Hull et al (2015) showed decreased severity and duration of seizures in children with refractory epilepsy and autism after stimulation of vagus nerve. Moreover, they found the improvement in ASD symptoms not related to epilepsy, such as communication skills, or stereotyped behavior. Furthermore, considerable improvement in regulation of aggressive behavior and receptive communication skills were noted and maintained over 1 year. The biggest drawback of vagus nerve stimulation method is cost and requirement of invasive neurosurgery. However, recent studies confirmed the possibility of noninvasive transcutaneous stimulation of the vagus nerve with electrodes located in the auricular concha area that is densely innervated by branches of the vagus nerve (Fang et al 2016). Electrical stimulation of the cervical vagus nerve with handheld device represent another non-invasive method (Schoenen et al 2016). In preterm infants or high-risk infants, kangaroo care or massage therapy may increase vagal tone and promote optimal neurodevelopment (Feldman & Eidelman 2003). Similar preliminary data were obtained on children with ASD, as well (Escalona et al 2001).

This new clinical trial looks very interesting because it includes looking at predictors for responders:-

The specific aim of this study is to examine the effects of serial doses of propranolol on social interaction, and secondarily on language tasks, anxiety, adaptive behaviors, and global function in high functioning adults and adolescents with autism in a double-blinded, placebo-controlled trial. The investigators will also examine whether response to treatment can be predicted based upon markers of autonomic functioning, such as skin conductance, heart rate variability (HRV), and the pupillary light reflex (PLR), and whether anxiety can predict treatment response. The hypothesis is that social functioning and language abilities will benefit from serial doses of propranolol, and that those with the greatest degree of autonomic dysregulation, or the lowest functional connectivity, will demonstrate the greatest benefit from the drug.

Propanolol will be given on a titration schedule in which participants will begin with small doses (single capsules) of the drug and increase to a larger dosage (divided over 3 capsules) over the course of three weeks. Participants aged 15-24 years will undergo an MRI.

 Autonomic Dysfunction in Autism


Objective: To report a case series of clinically significant autonomic dysunction in ASD. 
Background:Autonomic nervous system (ANS) impairment has been increasingly recognized in autism spectrum disorders (ASD). Abnormalities in pupillary light reflex, resting heart rate, heart rate response to social cognitive tasks, respiratory rhythm, and skin conductance suggest that autonomic dysfunction is common in ASD and may play a role in the social, behavioral, and communication problems that are the hallmark of this neurodevelopmental disorder. This case series confirms the presence of clinically significant multisystem ANS dysfunction in ASD. 
Methods: Patients with a history of ASD who underwent an evaluation for ANS dysfunction at our institution were identified. Clinical features, findings on autonomic testing, and laboratory results were reviewed.
Results: Six patients with ASD underwent clinical and autonomic evaluation, ranging in age from 12 to 28, and autonomic symptom duration ranging from 10 months to 6 years. All reported postural lightheadedness, near-syncope, and rapid heart rate. Five reported significant gastrointestinal (GI) symptoms including constipation, diarrhea, and early satiety. Autonomic testing revealed an excessive postural tachycardia with head-up tilt (HUT) in all patients, with a mean heart rate (HR) increment of 50 bpm, mean maximum HR on HUT of 118 bpm, absence of orthostatic hypotension on HUT. Abnormal blood pressure profile with the Valsalva maneuver was identified in three patients. All five patients were diagnosed with orthostatic intolerance. Supine norepinephrine (NE) was low in three of the four patients tested and an inadequate rise in standing NE was noted in two of these patients. GI motility testing was performed in two patients, and suggested gastroparesis in one patient.
Conclusions: Clinically significant ANS dysfunction may occur in ASD, with symptoms suggestive of orthostatic intolerance and gastrointestinal dysmotility, and findings on autonomic testing demonstrating an excessive postural tachycardia.

Functional autonomic nervous system profile in children with autism spectrum disorder


Autonomic dysregulation has been recently reported as a feature of autism spectrum disorder (ASD). However, the nature of autonomic atypicalities in ASD remain largely unknown. The goal of this study was to characterize the cardiac autonomic profile of children with ASD across four domains affected in ASD (anxiety, attention, response inhibition, and social cognition), and suggested to be affected by autonomic dysregulation.


We compared measures of autonomic cardiac regulation in typically developing children (n = 34) and those with ASD (n = 40) as the children performed tasks eliciting anxiety, attention, response inhibition, and social cognition. Heart rate was used to quantify overall autonomic arousal, and respiratory sinus arrhythmia (RSA) was used as an index of vagal influences. Associations between atypical autonomic findings and intellectual functioning (Weschler scale), ASD symptomatology (Social Communication Questionnaire score), and co-morbid anxiety (Revised Children’s Anxiety and Depression Scale) were also investigated.


The ASD group had marginally elevated basal heart rate, and showed decreased heart rate reactivity to social anxiety and increased RSA reactivity to the social cognition task. In this group, heart rate reactivity to the social anxiety task was positively correlated with IQ and task performance, and negatively correlated with generalized anxiety. RSA reactivity in the social cognition task was positively correlated with IQ.


Our data suggest overall autonomic hyperarousal in ASD and selective atypical reactivity to social tasks.

The Vagus nerve as a means to affect the ANS 

Vagal Nerve Stimulation in Autonomic Dysfunction – A Case Study

Background: Autonomic nervous system function is influenced by the balance of the parasympathetic and sympathetic systems. Management for imbalance of these components causing dysfunction is largely focused on medications primarily improving cardiovascular tone. However, there appears to be an opportunity for therapy by modulating neurotransmission. Methods: Our patient is a nine year old female with history of intractable epilepsy and developmental delay related to confirmed genetic abnormalities and also complaints of episodic pallor, fatigue, light-headedness and headaches concerning for dysautonomia. Results: Our patient underwent vagal nerve stimulator (VNS) implantation for treatment of epilepsy and showed improvement of these symptoms at typical settings. Headup tilt test (HUTT) was subsequently performed and revealed normal findings and no subjective symptoms of autonomic dysfunction. A repeat HUTT was performed five months later with VNS output currents set to zero and revealed cardiovascular changes and clinical symptoms consistent with dysautonomia. With resumption of previous VNS settings, clinical symptoms resolved.

Conclusions: Neurotransmission from vagal afferents to brainstem nuclei is increased during VNS affecting multiple brainstem areas and the cerebral cortex, including regions controlling autonomic function. Studies have suggested a role for VNS in patients with clinical signs of autonomic dysfunction showing improvement in sympathovagal balance after VNS implantation. In our patient, we observed subjective and objective improvement in autonomic function. This initial case demonstrates a phenomenon that requires further study, may lead to improved understanding of autonomic function and the response to vagal nerve stimulation, and possibly a new indication for VNS therapy.

The autonomic nervous system, consisting of the sympathetic and parasympathetic branches, is a major contributor to the maintenance of cardiovascular variables within homeostatic limits. As we age or in certain pathological conditions, the balance between the two branches changes such that sympathetic activity is more dominant, and this change in dominance is negatively correlated with prognosis in conditions such as heart failure. We have shown that non-invasive stimulation of the tragus of the ear increases parasympathetic activity and reduces sympathetic activity and that the extent of this effect is correlated with the baseline cardiovascular parameters of different subjects. The effects could be attributable to activation of the afferent branch of the vagus and, potentially, other sensory nerves in that region. This indicates that tragus stimulation may be a viable treatment in disorders where autonomic activity to the heart is compromised.

The Vagus Nerve as a target to reduce inflammation
Regardless of its effects on the autonomic nervous system (ANS), we know from the research in earlier blog posts that vagus nerve stimulation can significantly reduce inflammation.  Here is an easy to read article as a reminder.

Vagus Nerve Stimulation Dramatically Reduces Inflammation

Stimulating the vagus nerve reduces inflammation and the symptoms of arthritis.

Healthy vagal tone is indicated by a slight increase of heart rate when you inhale, and a decrease of heart rate when you exhale. Deep diaphragmatic breathing—with a long, slow exhale—is key to stimulating the vagus nerve and slowing heart rate and blood pressure, especially in times of performance anxiety.
A higher vagal tone index is linked to physical and psychological well-being. Conversely, a low vagal tone index is associated with inflammation, depression, negative moods, loneliness, heart attacks, and stroke.

There are many ways put forward to  stimulate the vagus nerve simply without electrical devices. Here is one list I came across:-

1.     Slow deep breathing. An example would be to breathe in slowly for a count of 4 and out for a count 6 to 8. The average normal breathing rate is between 12 and 14 per minute. This slow breathing reduces it to 6 to 7 per minute.
2.     Any exposure to cold. eg rinse your hands and face in cold water.
3.     Singing, chanting, gargling and humming
4.     Laughter
5.     Restorative yoga postures such as the cat cow posture and downward dog
6.     Meditation.
7.     Evoking the emotions of love, compassion and empathy.
8.     Exercise
9.     Massage/acupuncture, acupressure
10. Intermittent fasting

I found re-reading this old post interesting

Drinking Baking Soda for Vagal Nerve Stimulation?

It prompted me to order some potassium bicarbonate.


I think when you read about what the Autonomic Nervous System (ANS) does in your body you are likely to be able to judge whether or not it may be dysfunction. Hopefully the research will identify reliable markers, whether it is heart rate variability (HRV) or pupillary light reflex (PLR).
I do not think Autonomic Nervous System (ANS) dysfunction is a cause of autism, but it may be a consequence of it. Correcting any such dysfunction may have an impact ranging from trivial to profound.
I know that some readers of this blog have been using Propranolol for some time already. It has been very well researched, by the standards of autism. Being a cheap generic drug, there is little interest to spend $8 million in Europe to have it approved for autism, or the $20 million needed in the US. 
It should be noted that while Propranolol is a very widely used drug it does have side effects and interactions. Some other autism drugs used off-label do reduce blood pressure.
Propranolol is a competitive antagonist of beta-1-adrenergic receptors in the heart. It competes with sympathomimetic neurotransmitters for binding to receptors, which inhibits sympathetic stimulation of the heart. Blockage of neurotransmitter binding to beta 1 receptors on cardiac myocytes inhibits activation of adenylate cyclase, which in turn inhibits cAMP synthesis leading to reduced PKA production. This results in less calcium influx to cardiac myocytes through voltage gated L-type calcium channels meaning there is a decreased sympathetic effect on cardiac cells, resulting in antihypertensive effects including reduced heart rate and lower arterial blood pressure.

One side effect of Propranolol is low heart rate (bradycardia), but some people do have too high a heart rate.
Propranolol is a so-called negative inotropic agent, meaning it reduces the strength of contractions of heart muscle. This is why it reduces blood pressure.
Negative inotropic effects can be additive, which means not surprisingly if you take another negative inotropic agent, like an L-type calcium channel blocker, you have to be careful.
There are medical conditions for which the combined use of Propranolol and Verapamil has been suggested, but at the high doses often used this looks rather unwise.
There are interactions between Propranolol and many drugs; note that Verapamil will raise the serum level of propranolol.
The good news is that the dosage often effective in autism is quite low.

The adult dose for Migraine Prophylaxis is up to 240mg a day.  Some of the regular pediatric doses are also huge, compared to the “autism dosage” which can be 40mg of even less.
The initial paper we looked at in this post, from ultra-sceptical that autism can be treated England, concluded:

 “… randomised controlled trials are warranted to explore the efficacy of propranolol in managing EBAD (emotional, behavioural and autonomic dysregulation) in ASD”
Are severe headaches that occur in some autism another possible predictor of Propranolol responders?

Is stuttering another symptom to look out for?

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.

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.


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.

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 

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:-


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 and, 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.