Process Flow Diagram for Respen-A

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New Study on Respen-A in Autism Spectrum Disorders Shows Respen-A to Have a Significant Effect in Treating the Core Symptoms.

Dr. Anju Usman specializes in Autism Spectrum Disorders (ASD). She has found that many of her patients with ASD have a single or double mutation on their MAO-A gene. Dr. Usman stated that those patients with a double mutation often failed to respond to traditional or complementary treatments and therapies. Respen-A is a homeopathic topical disc containing a 12C dilution of reserpine, which is a very old blood pressure medication. Resperine has been shown to double the activity of MAO-A. Thus, Dr. Usman evaluated the effect of Respen-A in 9 of her patients having MAO-A mutations, utilizing the Autism Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS). The ATEC is a parent-rated measure and the CARS is completed by a health professional. Research has shown a significant correlation between total ATEC and CARS scores. Evaluations were conducted before starting the Respen-A (“Pre” Score) and after wearing the Respen-A topical disc for 3 months (“Post” Score).

The ATEC is a validated tool developed by the Autism Research Institute to evaluate the effectiveness of a treatment to improve the core symptoms of ASD. The core symptoms of ASD are impaired speech/language, impaired socialization, impaired sensory/cognitive awareness, and restrictive health/physical behaviors. The ATEC scores consist of individual scores for each category of core symptoms as well as a total score which is the sum of all of the symptom category scores. The higher the score, the greater the severity of the symptoms.

ATEC scores range from zero to 180. If a child scores zero or close to zero, that child can no longer be distinguished from non-autistic children and thus can be considered fully recovered. The important benchmarks in scoring are as follows:

A total ATEC score < 30. This level places the child in the top 10 percentile. A child with score of less than 30 – or, better still, less than 20 – would have some ability to conduct normal, two-way conversations, and more or less behave normally. Such children have high chances of leading normal lives as independent individuals.

A total ATEC score < 50. This places the child in the 30th percentile level. The child has good chances of being semi-independent. More importantly, he or she will not likely need to be placed in an institution or residential home. For many parents of autistic children, being able to achieve improvement up to this level is already considered very significant.

A total ATEC score > 104. Even though the maximum score is 180, any person with a score of more than 104 would already be in the 90th percentile, and be considered very severely autistic.

The CARS is a 15-item behavioral rating scale developed to identify autism as well as to quantitatively describe the severity. The items are: I. Relating to People; II. Imitation; III. Emotional Response; IV Body Use; V. Object Use; VI. Adaptation to Change; VII. Visual Response; VIII. Listening Response; IX. Taste, Smell, and Touch Response and Use; X. Fear or Nervousness; XI. Verbal Communication; XII. Nonverbal Communication; XIII. Activity Level; XIV. Level and Consistency of Intellectual Response; and XV. General Impressions. Each item is scored from 1 to 4 in 0.5 intervals. A total score of 15-29.5 is considered nonautistic; a score of 30-36.5 is considered mild to moderate autism; and a score of 37-60 is considered moderate to severe autism.

Eight of the nine patients evaluated had moderate to severe autism and one patient had mild to moderate autism according to their baseline total CARS score. The improvements in the total CARS scores were significant with a p value of 0.01.

The total ATEC scores showed highly significant improvements with a p value of 0.001.

Because of the strong effect size of the Respen-A, the power of the study was well above .80, which is the acceptable power for scientific studies. The fact that Dr. Usman’s study only included 9 patients, the Respen-A homeopathic treatment would need to have a very strong effect size to show a statistical significant effect. The larger the study the less effect size of a treatment is needed to show statistical significance. For instance, it only takes one person wearing a very strong perfume to walk into a room for everyone in the room to notice the scent of the perfume. But if a person is wearing a weak perfume, it would take several people wearing that weak perfume before there would be a noticeable scent of the perfume in the room. Despite the very small number of patients analyzed in the study, Respen-A showed a highly statistical significant effect with a p value of 0.001. The p value measures the probability of getting these results by chance alone. A p value of 0.05 or less is considered statistically significant, meaning there is only 5 in 100 chances that the results were in error. The improvement in the total ATEC scores with patients applying the Respen-A topical disc for three months achieved a p value of 0.001, meaning there are only 1 in 1,000 chances that the improvements seen with the Respen-A disc were simply by chance alone.

Below are the Pre and Post scores for both the ATEC and the CARS. Evaluations were conducted before starting the Respen-A (“Pre” Score) and after wearing the Respen-A topical disc for 3 months (“Post” Score).

Patient ATEC

Speech/

Language

ATEC

Socialization

ATEC

Sensory/

Cognitive

ATEC

Health/Physical Behaviors

ATEC

Total

CARS

Total

Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post
1. 19 14 8 7 16 16 19 12 62 49 49 40
2. 11 11 15 15 19 16 30 29 75 71 46 42
3. 9 9 15 9 15 10 2 16 41 44 43 41
4. 14 14 15 15 20 19 46 41 95 89 57 57
5. 9 9 4 3 12 11 5 6 30 29 31 30
6. 13 11 13 11 13 12 22 15 61 49 46 41
7. 4 4 3 3 2 2 17 15 26 24 42 38
8. 22 24 33 38 29 32 41 56 125 150 68 69
9. 15 12 5 5 11 12 7 4 38 33 40 38

A study conducted at the New England Center for Children found that most therapies need to be started before age two and continued for at least a year before significant benefits may be noticed. Dr. Usman states, “Using Nutrigenomics, MAO-A SNPs and cholesterol levels to individualize treatment, the homeopathic Respen-A patches provided a statistically significant improvement in my patients. These results were unexpected because of the small study size, the older age of the patients and the chronic nature of their issues that improved in just 3 months.” The average age of the patients in the small Respen-A study was 13.5 years of age and patients showed significant improvement within just 3 months of starting Respen-A.

New Respen-A Disc that will be replacing Respen-A Blended Chord Disc

We are pleased to inform you that we have a new improved Respen-A™ disc that can now be shipped and stored at room temperature.  The new formulation referred to as simply, Respen-A™, is a 12C homeopathic dilution of reserpine and a 12C homeopathic dilution of a reserpine metabolite whereas the Respen-A™ Blended Chord that your child has been receiving is a 4X dilution of reserpine and 12C dilution of a reserpine metabolite.

Our goal in developing the new Respen-A™ formulation was to get the Respen-A™ stable at room temperature, but early reports from parents who have beta tested the new Respen-A™ formulation have stated that the new formulation has a superior effect in treating their child’s symptoms as compared to the Respen-A™ Blended Chord.  We have enclosed one example of a parent’s testimonial comparing the effect of the new Respen-A™ with the previous Respen-A™ Blended Chord.

In order to get the Respen-A™ stable at room temperature, the packaging had to be changed to the foil packaging which is gas impermeable and has a very low volume of air surrounding the disc in the package.  Unfortunately the foil packaging doesn’t allow a person to cut the disc in half and save the second half of the disc for the next day’s dose. Thus, you will need to apply the full disc each day.

Another benefit that we have seen with the new Respen-A™ disc is that L-tryptophan and/or 5-HTP doesn’t have to be supplemented as long as your child eats a serving of meat a day.  The meat can be poultry, fish, beef, lamb, bison, venison, pork etc.  Also inositol doesn’t have to be supplemented if your child is not on a gluten free diet.  If your child is on a gluten free diet, they will probably still need the inositol supplementation, but very likely at a lesser dose than they were requiring with the Respen-A™ Blended Chord.

The 2,000 mg of elemental calcium with breakfast daily is still required with the new Respen-A™ disc. The application instructions are the same for the new Respen-A™ disc as they were for the Respen-A™ Blended Chord with the exception that the new Respen-A™ disc can now be stored at room temperature.  For the longest possible shelf life, we recommend storing it in the refrigerator.

After January 1, 2013 the current Respen-A™ Blended Chord disc will no longer be available as it will be replaced by the new Respen-A™ disc.  If you have any questions or concerns, please call the pharmacy or the Respen-A™ nurse consult line, toll free 1-877-963-3338.

Testimonial from Parent Testing the New Respen-A™ Disc as Compared to the Respen-A™ Blended Chord Disc

Yesterday we put Jacob back on the regular Respen Blended Chord disc (half disc). I have 3 packs left (6 days) and wanted to use them before they expired. Compared to the new Respen-A full disc packaged in foil that we have been testing for you…Jacob struggled way more on the Blended Chord. He was more agitated, more upset with feeling like he was always into trouble, less patience with his brothers(!), more difficulty with being interrupted. He even told me he didn’t feel very happy on this disc as the other one! WOW!

SO, we absolutely love the new Respen-A disc compared to the blended chord. He is so much happier and compliant and reasonable. He still perseverates on things but can be easily encouraged to stop without feeling he’s in trouble. He never once has said, “It’s always my fault…”, on the new disc but that was one of the first things he started saying yesterday when we re-tried the blended chord disc. He sometimes has periods where we feel he may be winding up and getting silly but he’s happy and that is SO much more important to us. We haven’t had the “giddiness” that I first told you about. He’s just way more happy.

When Lyndel notices, then I KNOW there’s a difference! ;o)  I have listed below the benefits we have seen on the new Respen-A disc packaged in foil.

  • Being truly kind and patient with his littlest brother.
  • Very helpful even when he was engaged in his own interest. Normally, we’ve gotten a begrudging grunt and a slow response but he has been very helpful with a glad heart.
  • Better focus on his school work.
  • Easily calmed down after thinking he had been left at home by himself. (poor guy, I was home but I didn’t hear him call.) ;o(   But he calmed down so much more quickly and didn’t hold on to it.
  • Remembering to take his disc off at night by himself.
  • So good at being redirected or refocused. Normally, he gets mad or upset when we redirect him or refocus him because of his particular “interest”. It’s been awesome to actually be able to correct him and he is able to take it, process it and be teachable and change. AMAZING!!
  • He was able to take his shower without any prompts from me and then normally, he just stands and vegs’ out in the shower. He washed himself, shut the shower off and remembered to squeegie (sp?) the shower off…all without me telling him a thing! FANTASTIC!!!
  • The last time we cut and hauled wood, he had a major tantrum in the yard (I told you about that). Also, he normally has to be redirected again and again, “Jacob, get the logs, Jacob here, Jacob get another log, etc.”.   Today, he was focused, hard working and never complained once about working. He was so good and SO happy.   I do have to say that we noticed he was more “happy go lucky”, which made it easy to help him and he just laughed it off but still did what we had asked.
  • Jacob hasn’t been so focused on his particular “interest” these past few days/OCD.  He still talks about them BUT doesn’t hound us. Last night when I was using the computer, he asked if he could be on it, I told him to wait until I      was done, and then he sat next to me and waited patiently without bugging me. That’s big!
  • Also, he was always coming up to us with arms outstretched wanting to hug. As cute as it is for our 4 year old to do this, not so cute for a big kid. He has not done that at all with this new Respen-A™ disc. He is willing to receive hugs      just not always “needing” one.
  • Thirdly, we realized that Jacob had way more energy yesterday (especially noticed because we were cutting and hauling wood). He was so worn out last night and I’m sure it’s because he was so much more active! It was so good.

Inositol vs Gluten

The serotonin push from Respen-A Blended Chord is so great that we previously were stating that a small amount of gluten (about 1/4 to a whole wheat cracker, depending on the child) was needed every 1.5 to 2 hours throughout the day to keep up with the push.  We recently have discovered another avenue of keeping up with the serotonin push, besides supplementing gluten, and that is supplementing Inositol.

Inositol can be used in place of gluten and early reports show it may be superior.  500 mg to 1,000 mg a day has been adequate in the release of serotonin to keep up with the turnover stimulated by Respen-A Blended Chord.  Inositol is available in a powder or capsule from various manufactures.  It virtually is tasteless and dissolves well in water.  Early reports show that a once a day dosing has been adequate, but depending on the child, you may find that dividing the dose up into three servings a day may be beneficial.

Respen-A Blended Chord Availability

We have developed a new formulation of the Respen-A, which you will hear referred to as Respen-A Blended Chord and it will be available, and take the place of the original Respen-A, July 1, 2011 via all pharmacies currently compounding the original Respen-A.

The rationale behind going from the original Respen-A to the Respen-A Blended Chord is the following:
There are two forms of MA0: MAO-A and MAO-B. The MAO-A:MAO-B ratio is much like a teeter-totter in that environmental factors that inhibit MAO-A activity usually boost MAO-B activity. Decreased activity in MAO-A is common in autism. A decrease in MAO-A results in a dysfunction in the mitochondria resulting in lactic acid production. This results in calcium phosphate being pulled from the compartmental stores in the body such as the bones. The phosphate neutralizes the acid, leaving high amounts of unbound calcium. This free calcium goes into the cells, such as mast cells, causing an inflammatory response and tissue damage. Tissue damage stimulates cholesterol production because cholesterol is needed for tissue repair. Thus, research shows that an MAO-A deficiency is associated with high cholesterol levels. But interestingly, many children with autism have low cholesterol levels. This may be explained by the fact that when MAO-B activity gets really high it inhibits production of cholesterol. This may also explain why high cholesterol levels often precede low cholesterol levels. Stress inhibits MAO-A. The decrease in the MAO-A:MAO-B ratio causes an increase in cholesterol. But as stress continues and becomes prolonged, the MAO-A activity becomes very low and the MAO-B activity becomes very high and this can result in very low cholesterol levels due to inhibition of cholesterol synthesis.

So we hypothesized that it may be beneficial to try and work on both sides of the MAO-A:MAO-B ratio. The Respen-A 4X formulation is aimed at increasing the MAO-A, but would Respen-A have a greater effect on the symptoms of autism if it worked on both sides of the equation; increasing the MAO-A and lowering the MAO-B? Thus, the Respen-A Blended Chord formulation was adopted. One of the metabolites of reserpine appears to boost MAO-A activity and decrease MAO-B activity. Thus the Respen-A Blended Chord is a 4x homeopathic dilution of reserpine and a 12C dilution of a reserpine metabolite.

The Respen-A Blended Chord was first tested in a small sample of 3 patients who had used the original Respen-A 4X formulation for 6-12+ months. On the Respen-A Blended Chord, they reported more initiation of language, better attention, better motor planning and dexterity, more affection, more empathy and awareness of others emotions and needs and a desire to help and respond to others. They also reported that a little bit of gluten every 1 1/2 -2 hours was an absolute MUST with the Respen-A Blended Chord.

We then increased the sample size of the Respen-A Blended Chord to 20 patients to see if these same benefits were consistent in a larger sample since often the response to a treatment can vary from individual to individual. The majority of the larger sample reported similar benefits as seen in the small 3 patient sample. Parents reported that they felt the Respen-A Blended Chord was superior to the Respen-A 4x.

So as of July 1, 2011, all pharmacies will begin compounding and dispensing the Respen-A Blended Chord and the original Respen-A 4x will no longer be available. The patient instructions are the same for Respen-A Blended Chord as for the original Respen-A 4x:

  • 2000 mg of calcium each morning with breakfast MUST be taken prior to putting on the disc.
  • All supplements that will negate the original Respen-A 4x will still in fact negate the new Respen-A Blended Chord (such as EFA’s, oils, Enhansa, high Vitamin D, etc)
  • A serving of meat must still be eaten daily to keep up with the serotonin turnover. (If meat cannot be eaten, you may supplement with 500mg of L-Tryptophan daily or100-150mg of 5-HTP 3-4 times a day.)
  • Also, a small amount of gluten (such as a 1/4-whole cracker, depending on the child) MUST be taken every 1 1/2 hours to 2 hours throughout the day if they are on a strict Gluten Free Diet.

    THE DIFFERENCE in the Respen-A 4x and Respen-A Blended Chord however, is that with the Respen-A Blended Chord it is recommended to start with only a 1/2 disc of the Respen-A Blended Chord as most patients have found the 1/2 disc to be the optimal dose of the Respen-A Blended Chord. Thus, if the patient is careful when opening the individual disc packages, so as to not tear the paper/foil backing, they can remove the disc, cut it in half with a pair of scissors and then place one half of the disc back into the package and reseal the paper/foil backing and place the package back in the refrigerator to be used the following day. Thus, a month’s supply of Respen-A Blended Chord may provide treatment for 2 months. (Note that if you are using less than 1/2 disc, you can only get the packaging to effectively reseal one time.)

    We are also holding a webinar on June 28, 2011 at 4:00pm Pacific Time to address the new formulation and our findings from those children that have tried both formulations. If you would like to join this webinar, please contact us at info@respen-a.com with your email address and we will make sure you are listed on the recipient list of our webinar invites. From what we have seen, we are very excited about the new Respen-A Blended Chord coming soon!

Yeast (Candida)

Yeast and bacteria make up the normal flora in the gastrointestinal tract.  Competition between the two species is what maintains the balance.   Antibiotics, poor diet, insufficient soluble fiber in the diet and poor gastric acid and digestive enzyme production can result in gastric dysbiosis in which yeast overgrowth occurs in the intestinal tract.  Probiotics and antifungal medications are commonly prescribed to fight dysbiosis but it can be a long and difficult battle. 

 Research has shown that prebiotics are more effective than probiotics in most cases to resolve dysbiosis.  Prebiotics are the optimal food for the bacterial flora in the intestines, whereas probiotics contain the favorable bacteria for the intestines.  The reason prebiotics have been more effective than probiotics at reversing dysbiosis is because it doesn’t do much good to just keep reintroducing the good bacteria into the intestinal tract if you don’t provide them with their optimal food source (soluble fiber).  Yeast is a very opportunistic organism, meaning they can thrive on a wide variety of food sources.  But the favorable bacterial flora in the intestines cannot.  The optimum food for the bacteria is soluble fiber,which our diets are becoming very deficient in.  Without this optimum food source of soluble fiber, the bacteria will not flourish, resulting in yeast overgrowth due to lack of competition from the bacteria.   Of course if the dysbiosis is due to the administration of antibiotics, then a probiotic would be indicated followed with prebiotics.

 A very good prebiotic is frucotooligosaccharides (FOS).  FOS is a soluble fiber consisting of sucrose and fructose but the way the two simple sugars are bound together, our body can’t digest them but the bacteria can flourish on them.  The exception to when FOS should not be supplemented is if a bad bacteria such as Klebsiella is present in the stool as this bad bacteria will flourish on FOS as well.  So the stools must be negative for the bad bacteria before supplementing FOS. 

 The key to supplementing FOS to get the most benefit is to take 2,000-3,000 mg of FOS all at one time each day.  The reason for this is as the bacteria utilize the FOS, they produce a protein the stimulates gene expression of two very important calcium binding proteins, Calbindin D9k and Calbindin D28k.  In order to stimulate gene expression, a particular protein must be present in a finite concentration, which is achieved if 2,000 –3,000 mg of FOS are taken all at once.  The Calbindin D9k is needed for calcium and other mineral absorption from the intestines.  The Calbindin D28k is needed to protect the cells from too much calcium influx that can result in cell damage and inflammation. 

 Many doctors and parents are reporting that the gastrointestinal problems including dysbiosis have resolved in their patients and children respectively after starting Respen-A with FOS.

Constipation

Constipation is common in autism due to the lack of gastric motility.  H2 receptors stimulate the production of gastric acid and digestive enzymes, which in turn stimulate intestinal motility.  So if the MAO-A activity is deficient, the H2 receptors don’t get adequate stimulation.  Many children or adults with autism are taking magnesium supplements orally or in the form of Epsom Salts baths to counteract the constipation. 

 Many parents have reported that their child’s constipation is resolved within days of starting the Respen-A.  It is recommended to stop the increased magnesium supplements when starting Respen-A as these can result in loose stools or diarrhea.  Also the increased magnesium intake can interfere with the calcium absorption that is necessary when using Respen-A.