Digestive Enzymes

Gastric disturbances such as decreased production of gastric acid, decreased digestive enzymes, poor absorption of nutrients, and dysbiosis are common in autism.  These gastric problems can be the result of deficient MAO-A activity.  MAO-A metabolizes histamine into the active H2 agonist.  H2 receptor stimulation by the H2 agonist stimulates the parietal cells in the stomach to secrete hydrochloric acid.  The hydrochloric acid helps breakdown the food in the stomach.  The low pH in the stomach as a result of hydrochloric acid secretion closes the sphincter from the esophagus into the stomach and opens the sphincter from the stomach into the duodenum, which is the beginning of the intestinal tract.  The intestines are alkaline so the acidic chyme (food from the stomach) lowers the pH of the duodenum.  The low pH of the duodenum stimulates the sphincter between the pancreas and the duodenum to open.  The opening of the sphincter between the pancreas and the duodenum stimulates the pancreas to contract and secrete digestive enzymes and secretin into the duodenum.  Secretin is the bicarbonate molecule for the intestines raising the pH of the duodenum back up to an alkaline pH.  The higher pH in the duodenum activates the digestive enzymes in the duodenum so that the food can be further broken down releasing the nutrients for absorption across the intestinal membrane.  So if MAO-A activity is deficient, the histamine is not converted to the H2 receptor agonist and the whole digestive process is hindered. 

 The active ingredient in Respen-A stimulates MAO-A activity resulting in H2 production, which in turn stimulates gastric acid and digestive enzyme production.  Many parents have reported that their child no longer needs the digestive enzymes after starting Respen-A.  Digestive enzymes can be taken with Respen-A but they may not be necessary.

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Pro-biotic vs Pre-biotic for dysbiosis in the gut

Many parents have reported success in getting the calcium into their child by putting it in muffin mix, pancake or waffle mix.  Heating doesn’t appear to affect it. Many children continue on the probiotics with Respen-A and many have stopped the probiotics.  Research has shown that prebiotics such as FOS are more effective than probiotics in reversing dysbiosis in the gut.  The FOS is a soluble fiber made up of sucrose and fructose but the way they are bound, we can’t digest them but they are an excellent source of food for the bacteria in our gut.  If we feed the bacteria what they thrive on the best, the bacteria will multiply and through competition keep the yeast in check returning balance to the gut.  In fact science has calculated that if you were to feed one bacterial cell what it needed and removed its waste, within a 24 hour period, that one bacterial cell would multiply to create the mass of an aircraft carrier.  So you can see that when you feed the bacteria its optimal food such as FOS, there is no need to keep supplying bacteria such as in a probiotic.  The only time you don’t want to use FOS is if your stools are positive for Klebsiella which is a bad bacteria in the gut.  You would need to get rid of the Klebsiella before taking the FOS or else it will floursih as well on the FOS. 

 One important thing about taking FOS, don’t divide up the dose as directed on the bottle to get the optimal effect of FOS.  As the bacteria eat the FOS, they produce a protein that stimulates our bodies’ gene expression of two very important calcium binding proteins, calbindin D9k and calbindin D28k.  The calbindin D9k is needed for calcium and other mineral absorption from the intestines and calbindin D28k protects the cells from too much calcium influx into the cells that can cause exitotoxicity and result in inflammation and cell damage.  Whenever you are stimulating gene expression, the protein concentration must be within a finite range.  2,000 -3,000 mg of FOS must be taken all at once in order to get this protein produced by the bacteria in the finite range to stimulate the production of the calcium binding proteins.

Soy Free Diet

The soy free diet has shown benefit in Autism Spectrum Disorders.  Soy is high in phyto-estrogens which have been shown to stimulate the estrogen receptors.  High estrogen receptor stimulation inhibits MAO-A.  Children with an ASD have decreased MAO-A activity and so by decreasing their estrogen, such as through a soy free diet, this will help prevent further inhibition of their MAO-A.  Unlike gluten and casein that may be added back into the diet in small amounts with children on Respen-A, soy should be avoided even though the child may be on Respen-A.

Casein Free Diet

The casein free diet has shown benefits similar to the gluten free diet in children with an Autism Spectrum Disorder.  Casein is a protein found in dairy products.  It is not a natural protein found in humans. The scientific rationale for the benefits seen from the casein free diet, is due to the hypersensitization of the mast cells that line the intestines causing them to over-react to this foreign protien, casein, when ingested.  The etiology of the hypersensitization of the mast cells is the mitochondrial deficiency caused by MAO-A deficiency, resulting in lactic acid production.  The build-up of lactic acid causes calcium phosphate to be pulled from storage compartments in the body such as the bones.  The phosphate neutralizes the acid, leaving free-unbound calcium in the blood.  The free-unbound calcium goes into the mast cells and excites them, causing them to become hypersensitive.  Normally, mast cells detecting casein in the gut would not react, but because of them being put on red-alert by the calcium, they actually over-react.   This results in an inflammatory response which contributes to digestive absorption problems.  This irritation in the gut results in more serotonin production by the gut.  (Please see the Gluten Free Diet post for the effects of increase serotonin production by the gut in ASD).

 The active ingredient in Respen-A is reserpine, which increases the activity of MAO-A, thus reducing the production of lactic acid.  This reduction in lactic acid production reduces the amout of free calcium influx into the mast cells.  Respen-A also, has an added benefit, reduces calcium by pushing it into the urine and into the bones, which in turn reduces the hypersensitivity of the mast cells.  Consequently, a child using Respen-A, overtime may find that they can tolerate some dairy products in their diet once again.

Gluten Free Diet

Many children, with an Autism Spectrum Disorder, have seen benefit from a gluten free diet.  The scientific rationale for this benefit is because gluten stimulates serotonin production and mobilization (release).  In ASD there is a deficiency in MAO-A activity, resulting in a build-up of serotonin because MAO-A breaks down serotonin into it’s active aldehyde.  This build-up of serotonin inhibits oxytocin nerve growth, increases in cortisol production, and increases beta-endorphin production, all of which are seen in ASD.  So gluten compounds the problem by stimulating the gut to produce and release more serotonin into the blood stream.  This is why a gluten free diet has been beneficial to many children with a spectrum disorder.

The active ingredient in Respen-A is reserpine.  Research shows that reserpine will double the activity of MAO-A.  Thus by increasing the activity of MAO-A with Respen-A, the serotonin level is decreased and converted into its active aldehyde metabolite.  Because of this breakdown of serotonin by MAO-A, serotonin must be replenished, such as through eating meat or taking the supplement of L-Tryptophan daily.  We have found that in some children on a gluten free diet, just eating meat or taking L-Tryptophan, isn’t adequate after being on Respen-A.  These children often show improvement in the first month to six months of using Respen-A and then they start to exhibit a return of their symptoms or become withdrawn, depressed, and sad.   We find that these children have needed to add back into their diet a little bit of gluten.  The reason is, L-Tryptophan from meat is the precursor to producing serotonin.  The serotonin that is produced, is then stored in vesicles in the cell.  The serotonin must then be released or mobilized from these vesicles into the synapse (the nerve junction), where it can be converted by MAO-A to its active aldehyde.  Gluten triggers the mobilization and release of the serotonin from the vesicles.

No EFA’s with Respen-A

No EFA Supplements When Using Respen-A™ or Respen™ Spray

Many parents have inquired as to why the need to discontinue the EFA supplements such as Flaxseed oil, Primrose oil, Fish oils and Omega3 when using the Respen-A™ disc or Respen™ Spray. We have found that these oils, which contain a high concentration of polyunsaturated fats, will negate the effects of Respen-A™ and Respen™ Spray.

A possible explanation for this phenomenon is that the body works in ratios, and this is a means of checks and balances. Some of the ratios in the body are sodium to potassium, calcium to magnesium, copper to zinc, and even polyunsaturated fats to saturated fats. Polyunsaturated fats contain double bonds, which is what makes them maintain their liquid state when refrigerated. Polyunsaturated fats are structural components in the cell membrane making the cell membrane fluid and flexible. The cell membrane has an inner and outer membrane with protein channels that must be lined up between the outer and inner cell membranes so that they form a channel that transverses the cell membrane, allowing the cell to import and export things. If the cell membrane were too fluid, these protein channels would not be lined up and the cell would not be able to import and export efficiently. Thus, the cell membrane also has saturated fats in the cell membrane, which are straight chains with single bonds and act like ties or rebar that help maintain the structural position of the protein channels in the cell membrane.

The body tries to keep the polyunsaturated fats and saturated fats in a specific ratio. The body has no control over what we feed it, so if we ingest a large concentration of polyunsaturated fats such as what is in the EFA supplements, the body will burn the excess polyunsaturated fats, trying to bring it back into balance with the saturated fats. Polyunsaturated fats with double bonds create lipid peroxides when they are broken (metabolized) in the body. Lipid peroxides are neurotoxic and they inhibit monoamine oxidase-A (MAO-A), which is the enzyme we are trying to boost with the reserpine in Respen-A™ or Respen™ Spray.

The best way to get a balance of saturated and polyunsaturated fats, is to eat whole foods such as meat, fish, and nuts as these contain both polyunsaturated fats and saturated fats in a ratio that is more balanced for our body.

Calcium is a MUST with Respen-A

Calcium Supplementation is a MUST with Respen™

 Many patients have verbalized some concern with the need to take 2,000mg of elemental calcium while using Respen™.  The rationale for the increased need of calcium is explained below.

 The active ingredient in Respen™ is reserpine.  Research has shown that reserpine increases monoamine oxidase-A (MAO-A) activity 2-fold.  MAO-A is the mitochondria enzyme involved in metabolizing histamine, serotonin and norepinephrine into their active aldehyde metabolites.  Histamine is metabolized by MAO-A into tele methylimidazoleacetaldehyde, which stimulates the H2 receptors in the brain and body.

 H2 receptor stimulation results in:

  • Increased gastric acid production
  • Increased digestive enzyme production and intrinsic factor for the absorption of Vitamin B12
  • Thyroid stimulation
  • Vasodilation of small arterioles
  • Pineal gland activation
  • Production of melatonin
  • Production of cyclic AMP
  • Major neurotransmitter in the hypothalamus
  • Dilation of the bronchioles
  • Stress regulation
  • Immune system regulation
  • Heat stress regulator for the brain and body

 Reserpine’s activation of MAO-A results in increased H2 receptor stimulation, which results in increased production of calcitonin by the thyroid gland.  Calcitonin pushes calcium from the blood into the bones.  H2 receptor stimulation also causes calcium from the blood to be excreted in the urine.  This results in decreased levels of calcium, which is a benefit of reserpine in that free unbound calcium can be too high in autistic children resulting in inflammation and excitatory cell destruction.  But reserpine lowers the blood calcium so much; 2,000 mg of elemental calcium is required to keep the blood calcium levels in the normal range. 

 It is recommended that the entire 2,000mg of calcium be taken all at once with breakfast because only 4-15% of the calcium supplemented is absorbed and it should be taken with adequate saturated fat and protein such as butter, whole milk, eggs or coconut butter if your child is on a casein free diet.  Saturated fat and protein is needed to adequately absorb calcium.  If calcium is taken later in the day, it can inhibit the parathyroid which can result in low blood calcium levels despite the calcium supplementation, thus it is recommended to take the calcium supplement all at once with breakfast. 

 Whenever hypercalciuria (calcium excreted in the urine) is initiated, magnesium becomes a blocker of calcium absorption from the intestine.  Thus, it is recommended a 4:1 or 5:1 ratio of calcium to magnesium when using Respen™.

 Symptoms of aggressiveness and irritability occur if the calcium intake is inadequate or poor absorption of the form of calcium being taken.  Most people report the best results with a calcium carbonate rather than a calcium citrate.  We recommend no vitamin D in the calcium supplement.  Below is a list of various calcium supplements that have been used with success:

  1. Calcium Carbonate powder from PCCA available only from the pharmacy where you get the Respen™.
    1. This powder goes into suspension easily in water or juice or can be mixed in applesauce, yogurt, etc and it has no taste.
    2. Requires frequent shaking if mixed in water or juice to keep it in a suspension while drinking.
    3. Requires a separate magnesium supplement to be taken i.e. magnesium oxide 500 mg a day.
    4. Certificate of Analysis states contains less than or equal to 3 ppm of lead
  2. Calcium Carbonate/magnesium oxide capsules available from the pharmacy where you get the Respen™.
    1. The capsules can be opened and the powder can be mixed with food or liquid. 
    2. 6 capsules are required to get 2,000 mg of elemental calcium
    3. Certificate of Analysis states contains 0.58 ppm of lead
  3. Calcium Carbonate liquid from Roxane laboratories available from the pharmacy or online.
    1. 1 teaspoon (5 ml) contains 500 mg of elemental calcium so 4 teaspoons (20 ml) are required to get 2,000 mg of elemental calcium
    2. Spearmint flavor
    3. Requires a separate magnesium supplement to be taken i.e. magnesium oxide 500 mg a day.
  4. TUMS Ultra 1,000
    1. Online information states that TUMS contain less than 3 ppm of lead.
    2. One tablet contains 400 mg of elemental calcium so 5 tablets would be required to get 2,000 mg of elemental calcium.
    3. Requires a separate magnesium supplement to be taken i.e. magnesium oxide 500 mg a day.
  5.  Calcium Carbonate Powder by NOW Nutritionals
    1. Less than 0.3ppm  of lead
    2. This calcium comes from limestone
    3. Requires a separate magnesium supplement to be taken i.e. magnesium     oxide 500 mg a day.

  If you experience increased aggressiveness or irritability using a Calcium Carbonate supplement, the following may be an alternative form of calcium supplementation:

  1.  Calcium Lactate Powder from Standard Process Product No. 1925
    1. 1 level tablespoon equals 800 mg of elemental calcium so 2.5 level tablespoons are required to get 2,000 mg of elemental calcium
    2. Contains magnesium so supplemental magnesium would probably not be required.  The calcium to magnesium ratio is 5:1 so if constipation occurs may need to supplement with separate magnesium. 
    3. Has been reported to dissolve well in hot slightly acidic liquids like warm apple juice.
  2. Calcium Lactate tablets from NutritionGeeks.com
    1. 1 tablet contains 255 mg of calcium so 8 tablets would be required to get 2,000 mg of elemental calcium
    2. Requires a separate magnesium supplement to be taken i.e. magnesium oxide 500 mg a day.

      3.   Calcium Citrate available in powder or tablet from various suppliers. 

  1. May require a separate magnesium supplement to be taken i.e. magnesium oxide 250-500 mg a day