Respen-A Blended Chord Availability
June 7, 2011 2 Comments
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!
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Hi, I’m interested in what you are discussing about the MAOA:MAOB ratio being related to cholesterol synthesis. I tried to look up more information about this online but couldn’t find any papers discussing this role of MAO in particular. Do you have any journal articles that discuss this that I could read to learn more?
MAO-A metabolizes serotonin, histamine and norepinephrine. MAO-B metabolizes dopamine. MAO-A activity declines in MS, many neurodegenerative diseases and in aging, whereas MAO-B activity increases (Saura J. et al, 1994; Andersen O. et al, 1981; Davidson D. et al, 1977; Fowler J.S. et al, 1997; Kornhuber J. et al, 1989; Kumar M.J. & Andersen J.K., 2004; Arai Y. & Kinemuchi H., 1988). Numerous factors can inhibit MAO-A activity and increase MAO-B activity i.e. lipid peroxidation, elevated estrogen levels, toxins such as mercury, and stress (Ma Z.Q. et al, 1995; Shemyakov S.E., 2001; Volchegorskii I.A., et al, 2004; Chevillard C. et al, 1981). The decrease in the ratio of MAO-A: MAO-B accounts for the laboratory indices and symptoms associated with aging and many neurodegenerative diseases as described in the following.
Research shows that there is an age-related decline in ATP production (Savitha S. et al, 2005). A decrease in the MAO-A:MAO-B ratio results in a decrease in the mitochondria complex I activity (NADH dehydrogenase) and alpha-ketoglutarate dehydrogenase (KGDH) which impedes ATP production (Gluck M.R. & Zeevalk G.D., 2004; Bai et al, 2005; Kumar M.J. et al, 2003). KGDH catalyzes the formation of Acetyl CoA which provides the substrate for the mitochondrial complex I. NADH dehydrogenase is needed to relieve the reduced NADH of the hydrogen accepted so that NAD+ can continue to accept hydrogens in the Krebs cycle. Thus, a decrease in the KGDH and NADH dehydrogenase results in a decrease in ATP production. Deficiency in mitochondrial complex I activity has been associated with many neurodegenerative diseases and the aging process (Bai Y. et al, 2005).
ATP is needed for activation of ubiquitin in the cells to prevent the accumulation of proteins in the cytosol. Proteins that are damaged, folded incorrectly or like cyclin at the end of mitosis are no longer needed, are deposited in the cytoplasm of the cell and are then tagged by ubiquitin for degradation into peptides to be recycled. The degradation of the ubiquitinated proteins requires ATP and hydrolysis by proteasomes. Deficiency of ATP results in the accumulation of these ubiquitinated proteins. (Marieb E., Human Anatomy and Physiology, 2001). An accumulation of these ubiquitinated proteins is associated with aging and neurodegenerative disease such as Alzheimer’s (Li Z. et al, 2004). As the cytosolic proteins accumulate, the cell volume increases disproportionately to the cell membrane surface area. The cell membrane will become inadequate to import and export necessary nutrients and wastes for the cell. This increase in cell volume:surface area ratio stimulates mitosis which temporarily relieves the problem. Inadequate ATP production will result in the same increase in cell volume:surface area ratio in the two daughter cells, again stimulating mitosis. Each mitotic division results in the shortening of the telomeres and eventual apoptosis. (Marieb E., Human Anatomy and Physiology, 2001).
The metabolism of catecholamines results in H2O2 or ammonia and urea production depending on the enzymatic processes. MAO-B metabolism of catecholamines such as dopamine results in H2O2 production, whereas MAO-A metabolizes histamine and results in urea and ammonia production (Kumar, M.J. & Andersen, J.K., 2004; Featherstone, R.M. & Berg, C.P., 1947). A decrease in the activity of KGDH and NADH dehydrogenase is directly correlated to an increase in H2O2 (Tretter, L. & Adam-Vizi, V., 2000). Increased H2O2 production taxes the supply of catalase since catalase is needed to metabolize H2O2. Research shows that H2O2 production is increased in aging and catalase is decreased in aging and exogenous catalase has been shown to reverse the effects of photoaging and aging on the skin (Shin et al, 2005). Increased H2O2 production results in increased advanced glycated endproducts (AGEs) which are cytotoxic and are components of the beta-amyloid plaques associated with Alzheimer’s and aging (Deuther-Conrad, W. et al, 2001). AGEs have been shown to increase the activity of MAO-B (Jiang, J.M. et al, 2004). Thus, a perpetuating cycle is established in that an increase in MAO-B activity generates an increase in H2O2 production, which precedes an increase in AGE formation, and AGE production increases the MAO-B activity.
MAO-A is the predominant amine-oxidizing enzyme in the neurons, whereas MAO-B is the predominant amine-oxidizing enzyme in the astrocytes (Nagatsu T., 2004; Squires R.F., 1997; Ekblom J. et al, 1993). Aging and many neurodegenerative diseases such as Multiple Sclerosis, Parkinson’s disease and Alzheimer’s are associated with an increase in the number of astrocytes and a decrease in neurons (Geinisman Y. et al, 1978; Casu M.A. et al, 2002; Hirsch E.C. et al, 2005; Ho G.J. et al, 2005). Astrocytes produce alanine and glutamate (Feldman et al, Emory University, 2000). Alanine can interfere with cysteine and tyrosine residues on MAO-A resulting in decreased MAO-A activity (Ma J. & Ito A., 2002; Vintem A.P. et al, 2005). Alanine may interfere with the electron transfer to the FAD that is required for MAO-A catabolism activity to produce active monoamine neurotransmitters. A single amino acid substitution of alanine in a proteasome subunit results in impaired protein degradation and significantly hypersensitizes the cells to oxidative stress and cell death (Li Z. et al, 2004).
Also increased alanine may compete with amino acid transport that would further impede balanced protein synthesis. There is evidence that changes in the concentrations of the monoamine neurotransmitters within the brain are associated with changes in mental processes, with disorders of movement, and some neuropsychiatric diseases. Deficient neurotransmitter will be synthesized if competition between amino acids for the carriers transporting them into the cerebral cells causes exclusion of a large proportion of any of the aromatic amino acid precursors from the brain (Daniel P.M. et al, 1976).
Caloric restriction has been shown to increase longevity (Spindler S.R., 2005). Alanine can be synthesized from intermediates of glucose metabolism in well-fed persons. Under fasting conditions, alanine, derived from protein breakdown, is converted to pyruvate for the synthesis of glucose (Cold Spring Harbor Laboratory and European Bioinformatics Institute, 2003). Alanine aminotransferase (ALT), the enzyme that synthesizes alanine via transamination of pyruvate, is elevated in people who had significantly higher body mass index, waist circumference, serum triglycerides, total-cholesterol:HDL-cholesterol ratio, and degree of insulin resistance (Schwimmer J.B. et al, 2005; Shen Y.H. et al, 2005; Marchesini G. et al, 2005). ALT strongly correlates with body mass, age and gender with the highest levels in elderly men with higher body mass index (Moranska I. et al, 2004; Bryhni B. et al, 2005; Lai S.W. et al, 2001).
Below is one published research abstract for your review specifically correlating increased cholesterol with decreased MAO-A activity. To summarize the above and why a decrease in MAO-A activity is correlated with increased cholesterol: Cholesterol is needed for all tissue repair. Decreased MAO-A activity results in alpha ketoglutarate dehydrogenase inhibition which prevents pyruvate from being able to enter the Krebs Cycle and instead it is converted to alanine. This results in higher alanine concentrations which in turn inhibit MAO-A further and can debilitate the proteasomes so then the ubiquitin tagged proteins build up in the cells causing cell destruction. Also the decreased MAO-A activity inhibits NADH dehydrogenase so the NAD can’t deliver its hydrogens to the electron transport chain. This results in lactic acid production. This causes calcium/phosphate to be pulled from compartmental stores such as the bones. The phosphate breaks off and neutralizes the acid leaving high amounts of unbound calcium. This results in increased calcium influx into the cells and cell destruction all of which increases the need for more cholesterol production to repair the tissue damage.
Med Sci Monit. 2008 Feb;14(2):CR57-61.
Lipid levels are associated with a regulatory polymorphism of the monoamine oxidase-A gene promoter (MAOA-uVNTR).
Brummett BH, Boyle SH, Siegler IC, Zuchner S, Ashley-Koch A, Williams RB.
Source
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. brummett@duke.edu
Abstract
BACKGROUND:
The monoamine oxidase-A (MAOA) gene plays a vital role in the metabolism of neurotransmitters, e.g, serotonin, norepinephrine, and dopamine. A polymorphism in the promoter region (MAOA-uVNTR) affects transcriptional efficiency. Allelic variation in MAOA-uVNTR has been associated with body mass index (BMI). We extended previous work by examining relations among this polymorphism and serum lipid levels.
MATERIAL/METHODS:
The sample consisted of 74 males enrolled in a study of caregivers for relatives with dementia. Regression models, adjusted for age, race, group status (caregiver/control), and cholesterol lowering medication (yes/no), were used to examine associations between high verses low MAOA-uVNTR activity alleles and total cholesterol, HDL, LDL, VLDL, LDL/HDL ratio, triglycerides, and BMI.
RESULTS:
Higher total cholesterol (p<0.03), LDL/HDL ratio (p<0.01), triglycerides (p<0.02), and VLDL (p<0.02) were associated with low activity MAOA-uVNTR alleles. HDL and LDL were modestly related to MAOA-uVNTR activity, however, they did not reach the conventional significance level (p<0.07 and p<0.10, respectively). BMI (p<0.74) was unrelated to MAOA-uVNTR transcription.
CONCLUSIONS:
The present findings suggest that MAOA-uVNTR may influence lipid levels and individuals with less active alleles are at increased health risk.
PMID: 18227761 [PubMed – indexed for MEDLINE] PMCID: PMC2759533 Free PMC Article