Sodium benzoate (Cinnamon) trialed for Schizophrenia (Adult-onset Autism)

Regular readers will have noticed that behavioral diagnosese like autism, ADHD, schizophrenia or even intermittent explosive disorder (IED) do not impress me.  I think that patients deserve a biological diagnosis from a neurologist.

To me, Schizophrenia might as well be called adult-onset autism and ADHD be called autism-lite.

We have already seen an overlap in the genetics/channelopathies of these three conditions.

Schizophrenia affects adults that developed “normally” as children and so they do not have the physical brain damage that has been shown to occur in many cases of autism.  According to Courchesne, the physical abnormalities he finds in autistic brains have occurred before most children even get diagnosed (before 3-5 years of age).  The young brain does remain plastic and this appears to explain why some children make excellent progress.  The various dysfunctions in utero and thereafter have caused some structural abnormalities in the brain.  In schizophrenia, the dysfunctions occur well after the brain has matured; so the result is different.  There are nonetheless very many similarities both in the underlying genetics and also in the observed behaviors.

So I term Schizophrenia, adult-onset autism.  (Many years ago, autism was called child onset Schizophrenia).  Any therapies that show promise in adults with schizophrenia should be trialed in children and adults with autism.

Just as there are many different dysfunctions that can lead to autism, there will be many that lead to schizophrenia.  I believe that there will be a wide overlap between those two groups of dysfunctions.

Back to Sodium Benzoate, Cinnamon and Schizophrenia

In my last post I started to look at Parkinson’s and COPD (severe asthma) and I suggested that the same anti-oxidant gene DJ-1 might also be relevant to autism.

I proposed that sodium benzoate, taken in the form of cinnamon, might be a useful therapy.

Having received a comment that some people with autism do not find sodium benzoate agreeable (it is found in carbonated drinks and is a common food additive), I did some more checking.

Firstly, if you are histamine intolerant, you should avoid cocoa, sodium benzoate and cinnamon.

For anyone unaffected, I found that a trial has already been carried out using Sodium Benzoate in Schizophrenia, with very promising results.

Add-on Treatment of (Sodium) Benzoate for Schizophrenia

DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer.

INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo.

MAIN OUTCOMES AND MEASURES The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment.

RESULTS Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms–20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health’s Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects.

CONCLUSIONS AND RELEVANCE Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia.

As to be expected, the proposed method of action is nothing to do with DJ-1 and oxidative stress.  They believe it is all about enhancing NMDAR-mediated neurotransmission.

Quite frankly, I do not mind why they think it works, or who is right.

For me what matters is that in adult-onset autism 1 g/day of sodium benzoate produced a 21% improvement in PANSS total score and in other rating scales. 

If you are wondering what is a PANSS score, according to Wikipedia:-

The PANSS or the Positive and Negative Syndrome Scale

To assess a patient using PANSS, an approximately 45-minute clinical interview is conducted. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers.

Positive scale

7 Items, (minimum score = 7, maximum score = 49)

·         Delusions

·         Conceptual disorganization

·         Hallucinations

·         Hyperactivity

·         Grandiosity

·         Suspiciousness/persecution

·         Hostility

Negative scale

7 Items, (minimum score = 7, maximum score = 49)

·         Blunted affect

·         Emotional withdrawal

·         Poor rapport

·         Passive/apathetic social withdrawal

·         Difficulty in abstract thinking

·         Lack of spontaneity and flow of conversation

·         Stereotyped thinking

General Psychopathology scale

16 Items, (minimum score = 16, maximum score = 112)

·         Somatic concern

·         Anxiety

·         Guilt feelings

·         Tension

·         Mannerisms and posturing

·         Depression

·         Motor retardation

·         Uncooperativeness

·         Unusual thought content

·         Disorientation

·         Poor attention

·         Lack of judgment and insight

·         Disturbance of volition

·         Poor impulse control

·         Preoccupation

·         Active social avoidance

PANSS Total score minimum = 30, maximum = 210

Note regarding Histamine

Some people have a deficiency of diamine oxidase, this means that their body cannot break down histamine in their food, or produced by their food.  They are histamine intolerant.

Histamine and histamine intolerance

There are also mast cell disorders:- Mast Cell Activation Syndrome (MCAS) and Mastocytosis that can affect some people with autism.

This area is not well understood and is subjective to diagnose and therefore treat.  Much will depend on which country you happen to live in.

Some people may have pollen allergies, but be histamine tolerant when it comes to food.  This just means that they produce enough diamine oxidase.

Some people have debilitating problems associated with mast cell disorders combined with histamine intolerance.

Histamine Intolerance

Many people with autism have allergies.  Some people have food intolerance.

In an allergic response, an allergen stimulates the release of antibodies, which attach themselves to mast cells. When histamine is released from the mast cells it may cause one or more of the following symptoms

· Eyes to itch, burn, or become watery

· Nose to itch, sneeze, and produce more mucus

· Skin to itch, develop rashes

· Sinuses to become congested and cause headaches

· Lungs to wheeze or have spasms

· Stomach to experience cramps and diarrhea

The release of histamine can be caused by almost any allergen. Examples include inhalant allergens (ragweed pollen, dust mite, etc.), drugs (penicillin, aspirin), stinging insect venoms, and foods (egg, wheat, milk, fish, etc.).

Histamine in Foods

There are many foods that contain histamine or cause the body to release histamine when eaten. These types of reactions are food intolerances, and are different from food allergy, in that the immune system is not involved in the reaction. The symptoms, however, can be the same as a food allergy.

An enzyme called diamine oxidase should break down any histamine that is absorbed from a histamine-containing food. So when you eat a food which contains histamine it should not affect you. However, some people have a low level of this enzyme. When they eat too many histamine-rich foods they may suffer ‘allergy-like’ symptoms such as headaches, rashes, itching, diarrhea, and vomiting or abdominal pain. This is called histamine intolerance.

Fermented foods may cause allergy symptoms because they are either rich in histamine or because yeast or mold is involved in the fermentation process.

Histamine-Rich Foods (including fermented foods):

· Alcoholic beverages, especially beer and wine.

· Anchovies, Mackerel

· Cheeses, especially aged or fermented cheese, such as parmesan

· Dried fruits such as apricots, dates, prunes, figs and raisins

· Fermented foods, such as pickled or smoked meats, sauerkraut

· Mushrooms, spinach, tomatoes, avocados

· Processed meats - sausage, hot dogs, salami, etc.

· Sardines, Smoked fish - herring, sardines, etc.

· Sour cream, sour milk, buttermilk, yogurt

· Soured breads, such as pumpernickel, coffee cakes and other foods made with large amounts of yeast.

· Vinegar or vinegar-containing foods, such as mayonnaise, salad dressing, ketchup, chili sauce, pickles, pickled beets, relishes, olives.

Histamine-Releasing Foods:

· Alcohol

· Bananas

· Chocolate

· Eggs

· Fish/Shellfish

· Milk

· Papayas

· Pineapple

· Strawberries

· Tomatoes

Mastocytosis Mistaken for Aspergers

One of the features I have in this blog is that I get to see what search terms people use to find this site.  Sometimes these search terms tell you some very interesting things.

Here is one such interesting search, somebody used today:-

    mastocytosis mistaken for aspergers

Even though I expect 90+% visitors to this blog are interested in more severe types of ASD than Asperger's, much here is likely to be applicable to some people with Asperger's.

There are several posts in this blog about the role of mast cells and how allergies cause them to degranulate.  In some people mast cell degranulation actually leads to pain.  Some people have an over-expression of mast cells, this is called Mastocytosis.

I made by own theory about seasonal autism flare-ups and mast cells, which I called Seasonal Autistic Mastocytosis.

Now we know that at least one person thinks their mastocytosis was mistaken for Asperger's. 




 

Seasonal Autistic Mastocytosis

 

 The degranulation process in a Mast cell. 1 = antigen; 2 = IgE; 3 = FcεRI; 4 = preformed mediators (histamine, proteases, chemokines, heparin); 5 = granules; 6 - Mast cell; 7 - newly formed mediators  leukotrienes, platelet-activating factor)

Source: Wikipedia 

Some of the most popular posts on my blog refer to my investigation into the role of histamine in autism.  The investigation was productive and lead to a highly effective treatment for the wild summertime flare-ups in autistic behaviour exhibited by Monty, aged 10 with ASD. 

Since I have found a therapy it is only reasonable to give the condition a name. 

Seasonal Autistic Mastocytosis (SAM)

Seasonal Autistic Mastocytosis (SAM), sometimes known as Airborne Autistic Mastocytosis, occurs when airborne allergens like pollen, cause mast cells in the eyes, nose, mouth and lungs to degranulate.  These mast cells contain many granules, themselves containing histamine, serotonin and heparin, a naturally occurring anticoagulant.  This mast cell activation also releases inflammatory cytokines, leukotrienes and platelet activating factor (PAF).  Some of these pro-inflammatory agents enter the brain and stoke up the ever-present neuro-inflammation, starting a downward spiral with further localized cytokine release.  In behavioural terms, the result is that all the earlier bad behaviours will return, but in a magnified form.  The observer may notice swings to aggression and self-injurious behaviour (SIB).  If the subject is verbal, he may complain of unpleasant itching on arms and legs, typical of mastocytosis.  The autistic subject, not understanding the reason for the itching, is likely to react with some form of tantrum, aggression or hitting that part of his body.

SAM should be considered even when only very minor symptoms of an allergy are visible, like red eyes or runny nose.  

The most effective therapy is to use mast cell stabilizers, but even a standard OTC H1 antihistamine will provide some relief within 20 minutes.  The dosage required to have an effect, may be much higher than the recommended dose for allergic rhinitis (hay fever), but should still be within safe limits.

 

An alternative therapy is simply to move to somewhere that is pollen free, even just for a weekend and observe the effect.

Depending on where you live, SAM may be possible for about 5 months of the year.

Mast cells are particularly present in the digestive tract, the lungs, skin, eyes, mouth and nose.  They undoubtedly also play a major role is asthma.

Mastocytic enterocolitis is a related condition.  This condition is acknowledged in the medical community.  I am not a gastroenterologist, but I think Messrs Wakefield and Krigsman may have really stumbled upon cases of Mastocytic enterocolitis, when they came up with their diagnosis of Autistic enterocolitis.  Incidentally, Krigsman recently published an interesting paper on genes and colitis in ASD.

Some of the frequently reported cases of GI problems in autism may also be caused by mast cell degranulation.  Some of the DAN doctors treat GI problems with mast cell stabilizers and allergists routinely prescribe them.

Note on Serotonin

Approximately 30% of people with autism have high blood serotonin; perhaps a contributing factor is serotonin released by the degranulation of mast cells.  We have already seen that there often appears to be central hypo-function of serotonin in autism (i.e. low brain serotonin).  The endocrine system functions using feedback loops, so high blood serotonin sends a signal to lower serotonin; thus you could get low brain serotonin but high blood serotonin.  Remember that serotonin does not cross the blood brain barrier.