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