The Yeast Accident / Parkinson’s Epiphany

I’ve about done myself in whilst hydroponic gardening radishes with my daughter for her science project. 🤢

Late in the project we had fungus gnats develop in the enclosure.

So the folks at the hydro store recommended an “all natural” “organic” fungicide/ pesticide...

But the plot thickens...After mixing it and applying it per the recommendations, I realize...

It’s 9.42% yeast!!!!
And I am allergic to yeast, and it’s a dread fungus!

So I think, “well I washed my hands in hot water” - but I started feeling weaker, shakier over the next few weeks while simultaneously going cold turkey on dairy. Then Friday I started smelling something like the substance itself in my sweat, breath - yuk! So I went to the doctor  and got some diflucan, and it seems to be zapping it. My Parkinson’s meds are working significantly better! I should progressively get somewhat better over the next month... my IGG allergy to yeast takes a week or so to onset, then a month of inflammation. Here’s what the urgent care doc gave me:

 

Further you will note that during the horror I specifically had to escalate my carbidopa.... making me wonder if the yeast controls us by making vitamin B6 or AADC! Note also that the night I crashed off my dairy free bid, I recovered well from this yogurt:
http://www.whitemountainfoods.com/probiotics.html

So those lactobacillus and other strains appear to attack the yeast. But also remember they sold me that yeast based fungicide for organic cultivation...  Makes me wonder if we’re getting loaded with yeast in organic fruits and vegetables.

 Looked into this further, it turns out that yeast does in fact produce vitamin B6!

Candida Sythesizes B6

So beware - B6 converts your Levodopa into dopamine so it doesn’t enter your brain and stops your gut, and candida or yeast in your gut produces vitamin B6!

Further explanation added 3/18/8:
Two Cofactors, vitamin B6 and AADC control how much Levodopa from your mesenteric system, including your medication which enters through your mesenteric system, gets to your brain. B6 and AADC together convert levodopa to dopamine and dopamine does not appreciably cross the blood brain barrier (BBB): Higher levels of B6 and AADC prevent more levodopa from crossing the BBB; lower levels allow more levodopa to cross the BBB. 90% of the serotonin and 50% of the body’s Levodopa are produced in the mesenteric system so it’s reasonable to estimate that AADC is abundant, being required for both Serotonin and Levodopa. Therefore if organisms such as over abundant yeast are injecting B6 directly at the origin location of both mesenteric and medication levodopa, that levodopa is quickly converted to dopamine and kept from the brain. Further, other citations in the literature indicate that yeast grows faster in higher levels of B6, so levels of yeast keep rising and this process snowballs.

Calculation Of Circulating Levodopa From The Mesenteric System, The Brain

Based on the paper “Substantial Production of Dopamine in the Human Gastrointestinal Tract “, 1997 by Eisenhofer et al , I wanted to see if I could develop a reasonable estimate for the amount of levodopa produced by the mesenteric system, and the amount of levodopa produced by the brain. The thinking is that we could put into perspective the contributions of your medicine, your gut, and your brain if your battling PD. So I used the information in the paper to perform calculations as follows:

How much Levodopa does the mesenteric system produce?

Levodopa molecular weight = 197.19g/MOL= 197.19 ng/nmol

Table 2,
States net mesenteric DOPA production as:
.65 nmol/min

197.19ng/nmol * .65 nmol/min = 128.17 ng/min,  * 1mg/1E6ng = .128E-3 mg/min

Mesenteric Daily Production:
.128mg/min * 60min/hr *24hrs/day = 184.32 mg/day
Comparable to 2 Sinamet 100/25 per day.

Please note that this is conservative because all the individuals studied in the paper had either gut cancer, pancreatic illness, or heart disease.

The article states: “Up to 46% of the DA formed in the body ... is derived from the gastrointestinal tract, pancreas, and spleen.” Given that some of the remainder is produced in the peripheral nervous system, perhaps a generous estimate is that 50% is produced by the brain. So we have about another 2 Sinamet being produced in a healthy brain. Estimates widely cited have indicated that brain production is 50% compromised in the PD affected by brain at onset. So the brain is producing about 1 Sinemet at onset of symptoms for PWP.

In summary :

Mesenteric System (gut, pancreas, spleen) - produces about 2 Sinamet per day

Parkinson’s brain at onset - 1 Sinamet per day

So this seems to imply that if you’re taking more that 1 Sinamet per day as a PWP, you’re fighting another Dragon besides brain disease (something in your periphery is either failing to produce levodopa, overactively converting levodopa to dopamine, and/or overactively destroying levodopa)  Possibilities include an overactive liver, overactive kidneys, and/or an unhealthy gut, unhealthy pancreas, improper vitamin B6 balance (and B6 is involved in 100
different processes), insufficient production of AADC enzyme and/or an unhealthy spleen.

Notice how very little levodopa is normally produced by your body. Depending on your stage of Parkinson’s and how much levodopa you’re taking, your medication dose can be 50x, 500x, or 5000x what the body normally produces. So it’s no wonder, results vary widely and side effects abound.

Find the article at:

https://academic.oup.com/jcem/article/82/11/3864/2866142

History and Background

 Collecting reference  papers here:

History of levodopa and dopamine agonists in Parkinson's disease treatment.

Tolosa E, et al. Neurology. 1998.

M

https://www.ncbi.nlm.nih.gov/m/pubmed/9633679/

How Does Carbidopa work?

Collecting References:

Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase

• Peter Burkhard
• , Paola Dominici
• , Carla Borri-Voltattorni
• , Johan N. Jansonius
 

https://www.nature.com/articles/nsb1101-963

Eisenhofer et al on mesenteric dopamine

Substantial Production of Dopamine in the Human Gastrointestinal Tract 

Graeme Eisenhofer Anders Åneman Peter Friberg Douglas Hooper Lars FåndriksHans Lonroth Béla Hunyady Eva Mezey

The Journal of Clinical Endocrinology & Metabolism, Volume 82, Issue 11, 1 November 1997, Pages 3864–3871, https://doi.org/10.1210/jcem.82.11.4339

Published:

01 November 1997

Article history

https://academic.oup.com/jcem/article/82/11/3864/2866142

Metabolism of Levodopa, Liver

collecting references here:

December 27, 1971

Absorption and Metabolism of Levodopa

B. Abrams, MD; Claude B. Coutinho, PhD; Arthur S. Leon, MD; et al

https://jamanetwork.com/journals/jama/article-abstract/340329?redirect=true

 Pharmacokinetics of Levodopa

Nutl John G.; Fellman, Jack H.

Clinical Neuropharmacology: March 1984 - Volume 7 - Issue 1 - ppg 35-50

Review: PDF Only

http://journals.lww.com/clinicalneuropharm/citation/1984/03000/pharmacokinetics_of_levodopa.2.aspx

 

 

Volume 296, Issue 7687, 26 December 1970, Pages 1341-1343

Preliminary Communications

LEVODOPA IN HEPATIC COMA

Author links open overlay panelJ.DParkesPSharpstoneRogerWilliams

https://doi.org/10.1016/S0140-6736(70)92362-7

http://www.sciencedirect.com/science/article/pii/S0140673670923627

     

Dual Beneficial Effects of (-)-Epigallocatechin-3-Gallate on Levodopa Methylation and Hippocampal Neurodegeneration: In Vitro and In Vivo Studies

• Ki Sung Kang, 
• Yujing Wen, 
• Noriko Yamabe, 
• Masayuki Fukui, 
• Stephanie C. Bishop, 
• Bao Ting Zhu

 

• Published: August 5, 2010
• https://doi.org/10.1371/journal.pone.0011951

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011951

September 01, 1997; 49 (3) Articles

Altered systemic iron metabolism in Parkinson's disease

G. Logroscino, K. Marder, J. Graziano, G. Freyer, V. Slavkovich, N. LoIacono, L. Cote and R. Mayeux

First published September 1, 1997, DOI: https://doi.org/10.1212/WNL.49.3.714

http://n.neurology.org/content/49/3/714.short 

Reviews in Endocrine and Metabolic Disorders

August 2001, Volume 2, Issue 3, pp 297–311 | Cite as

Understanding Catecholamine Metabolism as a Guide to the Biochemical Diagnosis of Pheochromocytoma

https://link.springer.com/article/10.1023%2FA%3A1011572617314?LI=true

 

Need Full Text

Papers By M. Hintz (Considered By Some As Controversial)

M. Hintz has written many papers discussing his theories regarding peripheral levodopa therapy, and his views on carbidopa and novel alternative PD treatments. While his papers have caused some controversy, and even notable backlash, nevertheless I think they are worth examining. In particular, the cited references appear to point towards a deeper understanding of peripheral systems impacting PD.

Amino acid management of Parkinson’s disease: a case study
https://www.dovepress.com/amino-acid-management-of-parkinsonrsquos-disease-a-case-study-peer-reviewed-article-IJGM

Parkinson’s disease managing reversible neurodegeneration
https://www.dovepress.com/parkinsonrsquos-disease-managing-reversible-neurodegeneration-peer-reviewed-fulltext-article-NDT

Parkinson’s disease-associated melanin steal
https://www.dovepress.com/parkinsonrsquos-disease-associated-melanin-steal-peer-reviewed-fulltext-article-NDT

Relative nutritional deficiencies associated with centrally acting monoamines
https://www.dovepress.com/relative-nutritional-deficiencies-associated-with-centrally-acting-mon-peer-reviewed-article-IJGM

The discrediting of the monoamine hypothesis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282597/

APRESS: apical regulatory super system, serotonin, and dopamine interaction
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157489/

The Parkinson's disease death rate: carbidopa and vitamin B6
https://www.dovepress.com/the-parkinson39s-disease-death-rate-carbidopa-and-vitamin-b6-peer-reviewed-fulltext-article-CPAA

citations:

1.	National Parkinson Foundation [webpage on the Internet]. What is Parkinson’s disease? Miami, FL: National Parkinson Foundation; 2014. Available from: http://www.parkinson.org/parkinson-s-disease/pd-101/what-is-parkinson-s-disease. Accessed July 19, 2014.
2.	Mayo Clinic [webpage on the Internet]. Diseases and conditions: Parkinson’s disease. Rochester, MN: Mayo Clinic; 2014. Available from: http://www.mayoclinic.org/diseases-conditions/parkinsons-disease/basics/treatment/con-20028488. Accessed July 19, 2014.
3.	SINEMET CR (carbidopa and levodopa) tablet, extended release [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc.; 2014. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=69e575b9-f8a5-494f-b736-2520ef505cb0. Accessed July 1, 2014.
4.	US Food and Drug Administration [webpage on the Internet]. Drugs@FDA: FDA approved drug products. Silver Spring, MD: US Food and Drug Administration; 2014. Available from: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed July 19, 2014.
5.	Airoldi L, Watkins CJ, Wiggins JF, Wurtman RJ. Effect of pyridoxine on the depletion of tissue pyridoxal phosphate by carbidopa. Metabolism. 1978;27(7):771–779.
6.	Hoyert DL, Heron MP, Murphy SL, Kung H. National Vital Statistics Report. Deaths: Final Data for 2003. Hyattsville, MD: National Center for Health Statistics; 2006. Available from: http://www.cdc.gov/nchs/data/nvsr/nvsr54/nvsr54_13.pdf. Accessed July 1, 2014.
7.	Daidone F, Montioli R, Paiardini A, et al. Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors. PLoS One. 2012;7(2):e31610.
8.	Andrews DW, Patrick RL, Barchas JD. The effects of 5-hydroxytryptophan and 5-hydroxytryptamine on dopamine synthesis and release in rat brain striatal synaptosomes. J Neurochem. 1978;30(2):465–470.
9.	Awazi N, Guldberg HC. On the interaction of 5-hydroxytryptophan and 5-hydroxytryptamine with dopamine metabolism in the rat striatum. Naunyn Schmiedebergs Arch Pharmacol. 1978;303(1):63–72.
10.	Hinz M. Depression. In: Kohlstadt I, editor. Food and Nutrients in Disease Management. Baton Rouge, FL: CRC Press; 2009:465–481.
11.	Hinz M, Stein A, Uncini T. The dual-gate lumen model of renal monoamine transport. Neuropsychiatr Dis Treat. 2010;6:387–392.
12.	Hinz M, Stein A, Uncini T. Amino acid management of Parkinson’s disease: a case study. Int J Gen Med. 2011;4:165–174.
13.	Hinz M, Stein A, Uncini T. Relative nutritional deficiencies associated with centrally acting monoamines. Int J Gen Med. 2012;5:413–430.
14.	Hinz M, Stein A, Uncini T. APRESS: apical regulatory super system, serotonin, and dopamine interaction. Neuropsychiatr Dis Treat. 2011;7:457–463.
15.	Stein A, Hinz M, Uncini T. Amino acid-responsive Crohn’s disease: a case study. Clin Exp Gastroenterol. 2010;3:171–177.
16.	Hinz M, Stein A, Neff R, Weinberg R, Uncini T. Treatment of attention deficit hyperactivity disorder with monoamine amino acid precursors and organic cation transporter assay interpretation. Neuropsychiatr Dis Treat. 2011;7:31–38.
17.	Hinz M, Stein A, Trachte G, Uncini T. Neurotransmitter testing of the urine: a comprehensive analysis. Open Access J Urol. 2010;2:177–183.
18.	Hinz M, Stein A, Uncini T. A pilot study differentiating recurrent major depression from bipolar disorder cycling on the depressive pole. Neuropsychiatr Dis Treat. 2010;6:741–747.
19.	Zhelyaskov DK, Levitt M, Udenfriend S. Tryptophan derivatives as inhibitors of tyrosine hydroxylase in vivo and in vitro. Mol Pharmacol. 1968;4(5):445–451.
20.	Ng LK, Chase TN, Colburn RW, Kopin IJ. Release of (3 H)dopamine by L-5-hydroxytryptophan. Brain Res. 1972;45(2):499–502.
21.	Stamford JA, Kruk ZL, Millar J. Striatal dopamine terminals release serotonin after 5-HTP pretreatment: in vivo voltammetric data. Brain Res. 1990;515(1–2):173–180.
22.	Ritvo ER, Yuwiler A, Geller E, et al. Effects of L-dopa in autism. J Autism Child Schizophr. 1971;1(2):190–205.
23.	Wuerthele SM, Moore KE. Studies on the mechanisms of L-dopa-induced depletion of 5-hydroxytryptamine in the mouse brain. Life Sci. 1977;20(10):1675–1680.
24.	Borah A, Mohanakumar KP. Long-term L-DOPA treatment causes indiscriminate increase in dopamine levels at the cost of serotonin synthesis in discrete brain regions of rats. Cell Mol Neurobiol. 2007;27(8):985–996.
25.	Karobath M, Díaz JL, Huttunen MO. The effect of L-dopa on the concentrations of tryptophan, tyrosine and serotonin in rat brain. Eur J Pharmacol. 1971;14(4):393–396.
26.	García NH, Berndt TJ, Tyce GM, Knox FG. Chronic oral L-DOPA increases dopamine and decreases serotonin excretions. Am J Physiol. 1999;277(5 Pt 2):R1476–R1480.
27.	Carta M, Carlsson T, Kirik D, Björklund A. Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain. 2007;130(Pt 7):1819–1833.
28.	Carta M, Carlsson T, Muñoz A, Kirik D, Björklund A. Serotonin–dopamine interaction in the induction and maintenance of L-DOPA-induced dyskinesias. Prog Brain Res. 2008;172:465–478.
29.	Everett GM, Borcherding JW. L-dopa: effect on concentrations of dopamine, norepinephrine, and serotonin in brains of mice. Science. 1970;168(3933):849–850.
30.	UniProt [webpage on the Internet]. UniProt. UniProt Consortium; 2014. Available from: http://www.uniprot.org/uniprot/?query=pyridoxal+AND+organism%3A%22Homo+sapiens+%5B9606%5D%22&sort=score. Accessed July 4, 2014.
31.	Paiardini A, Contestabile R, Buckle AM, Cellini B. PLP-dependent enzymes. Biomed Res Int. 2014;2014:856076.
32.	Nicotra A, Parvez S. Apoptotic molecules and MPTP-induced cell death. Neurotoxicol Teratol. 2002;24(5):599–605.
33.	Fangman A, O’Malley WE. L-dopa and the patient with Parkinson’s disease. Am J Nurs. 1969;69(7):1455–1457.
34.	Srimal RC, Dhawan BN. An analysis of methylphenidate induced gnawing in guinea pigs. Psychopharmacologia. 1970;18(1):99–107.
35.	Leon AS, Spiegel HE, Thomas G, Abrams WB. Pyridoxine antagonism of levodopa in parkinsonism. JAMA. 1971;218(13):1924–1927.
36.	Smythe GA, Edwards G, Graham P, Lazarus L. Biochemical diagnosis of pheochromocytoma by simultaneous measurement of urinary excretion of epinephrine and norepinephrine. Clin Chem. 1992;38(4):486–492.
37.	Verde G, Oppizzi G, Colussi G, et al. Effect of dopamine infusion on plasma levels of growth hormone in normal subjects and in agromegalic patients. Clin Endocrinol (Oxf). 1976;5(4):419–423.
38.	Weiner RI, Ganong WF. Role of brain monoamines and histamine in regulation of anterior pituitary secretion. Physiol Rev. 1978;58(4):905–976.
39.	Mason LJ, Cojocaru TT, Cole DJ. Surgical intervention and anesthetic management of the patient with Parkinson’s disease. Int Anesthesiol Clin. 1996;34(4):133–150.
40.	Volkow ND, Fowler JS, Gatley SJ, et al. PET evaluation of the dopamine system of the human brain. J Nucl Med. 1996;37(7):1242–1256.
41.	Checkley SA. Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness. Psychol Med. 1980;10(1):35–53.
42.	Nishino T, Lahiri S. Effects of dopamine on chemoreflexes in breathing. J Appl Physiol Respir Environ Exerc Physiol. 1981;50(4):892–897.
43.	Pollock JD, Rowland N. Peripherally administered serotonin decreases food intake in rats. Pharmacol Biochem Behav. 1981;15(2):179–183.
44.	Greenamyre JT. Glutamate–dopamine interactions in the basal ganglia: relationship to Parkinson’s disease. J Neural Transm Gen Sect. 1993; 91(2–3):255–269.
45.	Ward DS, Bellville JW. Effect of intravenous dopamine on hypercapnic ventilatory response in humans. J Appl Physiol Respir Environ Exerc Physiol. 1983;55(5):1418–1425.
46.	Morton JJ, Connell JM, Hughes MJ, Inglis GC, Wallace EC. The role of plasma osmolality, angiotensin II and dopamine in vasopressin release in man. Clin Endocrinol (Oxf). 1985;23(2):129–138.
47.	Seri I, Tulassay T, Kiszel J, et al. Effect of low-dose dopamine infusion on prolactin and thyrotropin secretion in preterm infants with hyaline membrane disease. Biol Neonate. 1985;47(6):317–322.
48.	Al-Damluji S, Rees LH. Effects of catecholamines on secretion of adrenocorticotrophic hormone (ACTH) in man. J Clin Pathol. 1987;40(9):1098–1107.
49.	Hoffman B, Lefkowitz R. Catecholamines and sympathomimetic drugs. In: Gillman AG, Rall TW, Nies AS, Taylor P, editors. Goodman and Gillman’s The Pharmacological Basis of Therapeutics. New York, NY: Pergamon Press; 1990.
50.	Levein NG, Thörn SE, Wattwil M. Dopamine delays gastric emptying and prolongs orocaecal transit time in volunteers. Eur J Anaesthesiol. 1999;16(4):246–250.
51.	Bell DG, McLellan TM, Sabiston CM. Effect of ingesting caffeine and ephedrine on 10-km run performance. Med Sci Sports Exerc. 2002;34(2):344–349.
52.	Bergerot A, Storer RJ, Goadsby PJ. Dopamine inhibits trigeminovascular transmission in the rat. Ann Neurol. 2007;61(3):251–262.
53.	Scanlon MF, Weightman DR, Shale DJ, et al. Dopamine is a physiological regulator of thyrotrophin (TSH) secretion in normal man. Clin Endocrinol (Oxf). 1979;10(1):7–15.
54.	Allen GF, Land JM, Heales SJ. A new perspective on the treatment of aromatic L-amino acid decarboxylase deficiency. Mol Genet Metab. 2009;97(1):6–14.
55.	Rubí B, Maechler P. Minireview: new roles for peripheral dopamine on metabolic control and tumor growth: let’s seek the balance. Endocrinology. 2010;151(12):5570–5581.
56.	Hinz M, Stein A, Uncini T. The discrediting of the monoamine hypothesis. Int J Gen Med. 2012;5:135–142.
57.	Carlsson A. A Half-Century of Neurotransmitter Research: Impact on Neurology and Psychiatry. Nobel Lecture, December 8, 2000. Available from: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2000/carlsson-lecture.pdf. Accessed July 4, 2014.
58.	Kandel ER. The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses. Nobel Lecture, December 8, 2000. Available from: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2000/kandel-lecture.pdf. Accessed July 4, 2014.
59.	The Royal Swedish Academy of Sciences. Advanced Information on the Nobel Prize in Chemistry 2001. Stockholm, Sweden: The Royal Swedish Academy of Sciences; 2001. Available from: http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2001/advanced-chemistryprize2001.pdf. Accessed July 4, 2014.
60.	Sweet RD, McDowell FH. Five years’ treatment of Parkinson’s disease with levodopa. Therapeutic results and survival of 100 patients. Ann Intern Med. 1975;83(4):456–463.
61.	Murphy SL, Xu JQ, Kochanek KD. Deaths: Final data for 2010. National vital statistics reports; vol 61 no 4. Hyattsville, MD: National Center for Health Statistics. 2013. Available from: http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_04.pdf. Accessed July 1, 2014.
62.	National Parkinson Foundation. The National Parkinson Foundation’s Helpline Speaks: Lessons from the 2011 Sinemet Shortage. Miami, FL: National Parkinson Foundation; 2012. Available from: http://www.parkinson.org/Files/PDFs/NPF-Content-Documents/White-Papers/NPF466-_2011-Sinemet-Shortage_WhitePaper-_Full-art. Accessed July 1, 2014.
63.	Mones RJ, Elizan TS, Siegel GJ. Analysis of L-dopa induced dyskinesias in 51 patients with Parkinsonism. J Neurol Neurosurg Psychiatry. 1971;34(6):668–673.
64.	Chase TN. Serotonergic mechanisms in Parkinson’s disease. Arch Neurol. 1972;27(4):354–356.
65.	Busch AE, Karbach U, Miska D, et al. Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998;54(2):342–352.
66.	Mayeux R, Stern Y, Williams JB, Cote L, Frantz A, Dyrenfurth I. Clinical and biochemical features of depression in Parkinson’s disease. Am J Psychiatry. 1986;143(6):756–759.
67.	Chan-Palay V, Höchli M, Jentsch B, Leonard B, Zetzsche T. Raphe serotonin neurons in the human brain stem in normal controls and patients with senile dementia of the Alzheimer type and Parkinson’s disease: relationship to monoamine oxidase enzyme localization. Dementia. 1992;3(5–6):253–269.
68.	Charlton CG, Mack J. Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain. Support for an excess methylation hypothesis for parkinsonism. Mol Neurobiol. 1994;9(1–3):149–161.
69.	Roche. Modpar [prescribing information’. Dee Why, Australia: Roche Products Pty Limited; 2010. Available from: http://www.roche-australia.com/content/dam/internet/corporate/roche/en_AU/files/central_nervous_agents/madopar-pi.pdf. Accessed July 20, 2014.
70.	Bertoldi M. Mammalian Dopa decarboxylase: structure, catalytic activity and inhibition. Arch Biochem Biophys. 2014;546:1–7.
71.	Wu F, Christen P, Gehring H. A novel approach to inhibit intracellular vitamin B6-dependent enzymes: proof of principle with human and plasmodium ornithine decarboxylase and human histidine decarboxylase. FASEB J. 2011;25(7):2109–2122.
72.	Cellini B, Montioli R, Oppici E, Voltattorni CB. Biochemical and computational approaches to improve the clinical treatment of dopa decarboxylase-related diseases: an overview. Open Biochem J. 2012;6:131–138.
73.	Bartlett MG. Biochemistry of the water soluble vitamins: a lecture for first year pharmacy students. Am J Pharm Educ. 2003; 67(2):Article 64.
74.	Palfreyman MG, Danzin C, Bey P, et al. Alpha-difluoromethyl DOPA, a new enzyme-activated irreversible inhibitor of aromatic L-amino acid decarboxylase. J Neurochem. 1978;31(4):927–932.
75.	DrugBank [webpage on the Internet]. Pyridoxal phosphate. DrugBank; 2013. Available from: http://www.drugbank.ca/drugs/DB00114. Accessed July 20, 2014.
76.	DrugBank [webpage on the Internet]. Carbidopa. DrugBank; 2013. Available from: http://www.drugbank.ca/drugs/DB00190. Accessed July 2014.
77.	National Institutes of Health [webpage on the Internet]. Vitamin B6: Dietary Supplement Fact Sheet. Bethesda, MD: National Institutes of Health; 2011. Available from: http://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/. Accessed July 20, 2014.
78.	Jansen MC, Bueno-de-Mesquita HB, Buzina R, et al. Dietary fiber and plant foods in relation to colorectal cancer mortality: the Seven Countries Study. Int J Cancer. 1999;81(2):174–179.
79.	Robinson K, Arheart K, Refsum H, et al. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group. Circulation. 1998;97(5):437–443.
80.	Cui R, Iso H, Date C, Kikuchi S, Tamakoshi A; Japan Collaborative Cohort Study Group. Dietary folate and vitamin b6 and B12 intake in relation to mortality from cardiovascular diseases: Japan collaborative cohort study. Stroke. 2010;41(6):1285–1289.
81.	Medrano MJ, Sierra MJ, Almazán J, Olalla MT, López-Abente G. The association of dietary folate, B6, and B12 with cardiovascular mortality in Spain: an ecological analysis. Am J Public Health. 2000;90(10):1636–1638.
82.	Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA. 2002;288(8):973–979.
83.	Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997;337(4):230–236.
84.	Centers for Disease Control and Prevention [webpage on the Internet]. Health data interactive. Atlanta, GA: Centers for Disease Control and Prevention; 2014. Available from: http://www.cdc.gov/nchs/hdi.htm. Accessed July 1, 2014.
85.	Baker AB. Treatment of paralysis agitans with vitamin B6 (pyridoxine hydrochloride). JAMA. 1941;116(22):2484–2487.
86.	Giardina G, Montioli R, Gianni S, et al. Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases. Proc Natl Acad Sci USA. 2011;108(51):20514–20519.
87.	Barbeau A. The pathogenesis of Parkinson’s disease: a new hypothesis. Can Med Assoc J. 1962;87:802–807.
88.	US Food and Drug Administration [webpage on the Internet]. Drugs@FDA: FDA approved drug products. Silver Spring, MD: US Food and Drug Administraiton; 2014. Available from: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed July 2014.
89.	Hoyert DL, Xu JQ. Deaths: Preliminary data for 2011. National vital statistics reports; vol 61 no 6. Hyattsville, MD: National Center for Health Statistics. 2012.

Parkinson's disease: carbidopa, nausea, and dyskinesia
https://www.dovepress.com/parkinson39s-disease-carbidopa-nausea-and-dyskinesia-peer-reviewed-fulltext-article-CPAA

citations:

1.	Hinz M, Stein A, Uncini T. Relative nutritional deficiencies associated with centrally acting monoamines. Int J Gen Med. 2012;5:413–430.
2.	GenomeNet. Homo sapiens (human):1644. Available from: http://www.genome.jp/dbget-bin/www_bget?hsa:1644+H01161+D00405+D00558+D01653+D03082+D08205. Accessed August 2, 2014.
3.	Mayo Clinic. Parkinson’s disease: treatments and drugs. 2014. Available from: http://www.mayoclinic.org/diseases-conditions/parkinsons-disease/basics/treatment/con-20028488. Accessed August 2, 2014.
4.	Sinemet CR® [prescribing information]. Available from: http://packageinserts.bms.com/pi/pi_sinemet_cr.pdf. Accessed August 2, 2014.
5.	Daidone F, Montioli R, Paiardini A, et al. Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors. PLoS One. 2012;7(2):e31610.
6.	Roche Australia. Madopar® [prescribing information]. Sydney: Roche Australia; 2010. Available from: http://www.roche-australia.com/content/dam/internet/corporate/roche/en_AU/files/central_nervous_agents/madopar-pi.pdf. Accessed August 2, 2014.
7.	Hinz M, Stein A, Uncini T. Amino acid management of Parkinson disease: a case study. Int J Gen Med. 2011;4:1–10.
8.	Hinz M, Stein A, Uncini T. Validity of urinary monoamine assay sales under the “spot baseline urinary neurotransmitter testing marketing model”. Int J Nephrol Renovasc Dis. 2011;4:101–113.
9.	Hinz M, Stein A, Uncini T. APRESS: apical regulatory super system, serotonin, and dopamine interaction. Neuropsychiatr Dis Treat. 2011;2011:7 1–7.
10.	Hinz M, Stein A, Uncini T. The dual-gate lumen model of renal monoamine transport. Neuropsychiatr Dis Treat. 2010;6:387–392.
11.	Stein A, Hinz M, Uncini T. Amino acid responsive Crohn’s disease: a case study. Clin Exp Gastroenterol. 2010;3:171–177.
12.	Hinz M, Stein A, Uncini T. Treatment of attention deficit hyperactivity disorder with monoamine amino acid precursors and organic cation transporter assay interpretation. Neuropsychiatr Dis Treat. 2011;7:31–38.
13.	Hinz M, Stein A, Uncini T. Urinary neurotransmitter testing: considerations of spot baseline norepinephrine and epinephrine. Open Access J Urol. 2011;3:19–24.
14.	Hinz M, Stein A, Uncini T. Monoamine depletion by reuptake inhibitors. Drug Healthc Patient Saf. 2011;3:69–77.
15.	Hinz M, Stein A, Uncini T. The discrediting of the monoamine hypothesis. Int J Gen Med. 2012;5:135–142.
16.	Hinz M, Stein A, Uncini T. 5-HTP efficacy and contraindications. Int J Gen Med. 2012;5:413–430.
17.	Carta M, Carlsson T, Muñoz A, Kirik D, Björklund A. Serotonin-dopamine interaction in the induction and maintenance of L-DOPA-induced dyskinesias. Prog Brain Res. 2008;172:465–468.
18.	Mones RJ, Elizan TS, Siegel GJ. Analysis of L-dopa induced dyskinesias in 51 patients with parkinsonism. J Neurol Neurosurg Psychiatry. 1971;34:668–673.
19.	Chase TN. Serotonergic mechanisms in Parkinson’s disease. Arch Neurol. 1972;27:354–356.
20.	Busch AE, Karbach U, Miska D, et al. Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998;54:342–352.
21.	Mayeux R, Stern Y, Williams JB, Cote L, Frantz A, Dyrenfurth I. Clinical and biochemical features of depression in Parkinson’s disease. Am J Psychiatry. 1986;143:756–759.
22.	Chan-Palay V, Höchli M, Jentsch B, Leonard B, Zetsche T. Raphe serotonin neurons in the human brain stem in normal controls and patients with senile dementia of the Alzheimer type and Parkinson’s disease: relation to monoamine oxidase enzyme location. Dementia. 1992;3:253–269.
23.	Charlton CG, Mack J. Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain: support for an excess methylation hypothesis for parkinsonism. Mol Neurobiol. 1994;9:149–161.
24.	UniProt. Search query results. Available from: http://www.uniprot.org/uniprot/?query=pyridoxal+AND+organism%3A%22Homo+sapiens+%5B9606%5D%22&sort=score. Accessed July 4, 2014.
25.	Andrews DW, Patrick RL, Barchas JD. The effects of 5-hydroxytryptophan and 5-hydroxytryptamine on dopamine synthesis and release in rat brain striatal synaptosomes. J Neurochem. 1978;30:465–470.
26.	Awazi N, Guldberg HC. On the interaction of 5-hydroxytryptophan and 5-hydroxytryptamine with dopamine metabolism in the rat striatum arch. Naunyn Schmiedebergs Arch Pharmacol. 1978;303:63–72.
27.	Zhelyaskov DK, Levitt M, Udenfriend S. Tryptophan derivatives as inhibitors of tyrosine hydroxylase in vivo and in vitro. Mol Pharmacol. 1968;4:445–451.
28.	Ng LK, Chase TN, Colburn RW, Kopin IJ. Research of [3H] dopamine by L-5-hydroxytryptophan. Brain Res. 1972;45:499–505.
29.	Stamford JA, Kruk ZL, Millar J. Striatal dopamine terminals release serotonin after 5-HTP pretreatment: in vivo voltammetric data. Brain Res. 1990;515:173–180.
30.	Ritvo ER, Yuwiler A, Geller E, et al. Effects of L-dopa in autism. J Autism Child Schizophr. 1971;1:190–205.
31.	Wuerthele SM, Moore KE. Studies on the mechanisms of L-dopa induced depletion of 5-hydroxytryptamine in the mouse brain. Life Sci. 1977;20:1675–1680.
32.	Borah A, Mohanakumar KP. Long-term L-DOPA treatment causes indiscriminate increase in dopamine levels at the cost of serotonin synthesis in discrete brain regions of rats. Cell Mol Neurobiol. 2007;27:985–996.
33.	Karobath M, Díaz JL, Huttunen MO. The effect of L-dopa on the concentrations of tryptophan, tyrosine, and serotonin in rat brain. Eur J Pharmacol. 1971;14:393–396.
34.	García NH, Berndt TJ, Tyce GM, Knox FG. Chronic oral L-DOPA increases dopamine and decreases serotonin excretions. Am J Physiol. 1999;277:R1476–R1480.
35.	Carta M, Carlsson T, Kirik D, Björklund A. Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain. 2007;130:1819–1833.
36.	Everett GM, Borcherding JW. L-DOPA: effect on concentrations of dopamine, norepinephrine, and serotonin in brains of mice. Science. 1970;168:847–850.
37.	Hinz M, Stein A, Cole T. Management of L-dopa overdose in the competitive inhibition state. Drug Healthc Patient Saf. 2014;6:93–99.
38.	US Department of Agriculture. Mucuna chochinchinensis (Lour) A Chev Available from: http://www.ars-grin.gov/cgi-bin/npgs/html/taxon.pl?70451. Accessed August 3, 2014.
39.	US Food and Drug Administration. FDA approved drug products. Available from: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed September 22, 2014.
40.	Google. Dyskinesia definition. Available from: https://www.google.com/search?sourceid=navclient&ie=UTF-8&rlz=1T4GGHP_enUS590US590&q=dyskinesia+definition. Accessed August 2, 2014.
41.	Barbeau A. L-dopa therapy in Parkinson’s disease: a critical review of nine years’ experience. Canada Med Assoc J. 1969;101:59–68.
42.	Krack P, Pollak P, Limousin P, et al. Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Brain. 1998;121:451–457.
43.	Fabbrini G, Brotchie JM, Grandas F, Nomoto M, Goetz CG. Levodopa-induced dyskinesias. Mov Disord. 2007;22:1379–1389; quiz 1523.
44.	Caparros-Lefebvre D, Blond S, Vermersch P, Pécheux N, Guieu JD, Petit H. Chronic thalamic stimulation improves tremor and levodopa induced dyskinesias in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1993;56:268–273.
45.	Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79:368–376.
46.	Fahn S. Levodopa in the treatment of Parkinson’s disease. J Neural Transm Suppl. 2006:1–15.
47.	Del Sorbo F, Albanese A. Levodopa-induced dyskinesias and their management. J Neurol. 2008;255 Suppl 4:32–41.
48.	Lewitt PA, Hauser RA, Lu M, et al. Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study). Neurology. 2012;79:164–169.
49.	Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE. A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med. 2000;342;1484–1491.
50.	Paiardini A, Contestabile R, Buckle AM, Cellini B. PLP-dependent enzymes. Biomed Res Int. 2014;2014;856076.
51.	Giardinia G, Montioli R, Gianni S, et al. Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to group II decarboxylases. Proc Natl Acad Sci U S A. 2011;108:20514–20519.
52.	Google Scholar. Search: [parkinson’s irreversible dyskinesias “l-dopa or levodopa”] with query prior to 1977. Accessed August 2, 2014.
53.	Schreck J, Kelsberg G, Rich J, Ward R. Clinical inquiries. What is the best initial treatment of Parkinson’s disease? J Fam Pract. 2003;52:897–899.
54.	Weiss JL, Ng LK, Chase TN. Long-lasting dyskinesia induced by L-dopa. Lancet. 1971;1:1016–1017.
55.	Greener M. New Hope for patients with Parkinson’s disease. Inpharma. 1999:3–4.
56.	Landers M. Exercise-Induced Neuroprotection in a Hemiparkinsonian 6-Hydroxydopamine Rat Model [doctoral thesis]. Las Vegas: University of Nevada; 2012.
57.	Oxford Dictionaries. Definition of antihistamine. Available from: http://www.oxforddictionaries.com/us/definition/american_english/antihistamine. Accessed August 2, 2014.
58.	Kemp SF, Lockey RF, Simons FE. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy. 2008;63:1061–1070.
59.	Wu F, Christen P, Gehring H. A novel approach to inhibit intracellular vitamin B6-dependent enzymes: proof with human and plasmodium ornithine decarboxylase and human histidine decarboxylase. FASEB J. 2011;25:2109–2122.
60.	Olson K. Poisoning and Drug Overdose. 4th ed. New York: McGraw-Hilll; 2003.
61.	Edriss H, Pfarr M. Acute respiratory distress syndrome, metabolic acidosis, and respiratory acidosis associated with citalopram overdose. 2014. Available from: http://pulmonarychronicles.com/ojs/index.php?journal=pulmonarychronicles&page=article&op=view&path%5B%5D=102&path%5B%5D=213. Accessed August 2, 2014.
62.	Scharman EJ1, Erdman AR, Wax PM, et al. Diphenhydramine and dimenhydrinate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2006;44:205–223.
63.	DrugBank. Pyridoxal phosphate. Available from: http://www.drugbank.ca/drugs/DB00114. Accessed July 20, 2014.
64.	DrugBank. Carbidopa. Available from: http://www.drugbank.ca/drugs/DB00190. Accessed July 20, 2014.
65.	Pitkin R. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington: National Academies; 1998.
66.	Hinz M, Stein A, Cole T. Parkinson’s disease death rate: carbidopa and vitamin B6 (PLP). Clinical Pharmacology: Advances and Applications. 2014;6:161–169.