Peer-reviewed published
scientific papers by Dr. Stein

Parkinson’s disease managing reversible neurodegeneration
Neuropsychiatric Disease and Treatment
Dove Press Journal
April 5, 2016

Abstract: Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neuro­degeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. Keywords: Parkinson’s disease, L-dopa, carbidopa, B6, neurodegeneration

Parkinson's disease-associated melanin steal.
PubMed - US National Library of Medicine National Institutes of Health
eCollection 2014

Abstract: Urinary dopamine fluctuations in the competitive inhibition state were first documented in 2009. At that time, it was noted that progressively higher daily dosing values of L-tyrosine decreased the magnitude of these fluctuations. While extensive statistical analysis has been performed by the authors since 2004, it was not until 2012 that a plausible explanation was formulated. In the process, correlations with L-tyrosine administration and the on/off effect of Parkinson's disease were defined. This paper documents the current knowledge with regard to the management of retrograde phase 1 dopamine fluctuations and investigates the hypothesis that they are caused by a melanin steal phenomenon. Keywords: L-dopa; dopamine; fluctuations; melanocyte

The Parkinson's disease death rate: carbidopa and vitamin B6
Clinical Pharmacology: Advances and Applications
Dove Press open access
October 2014

Abstract: The only indication for carbidopa and benserazide is the management of L-3,4-dihydroxyphenylalanine (L-dopa)-induced nausea. Both drugs irreversibly bind to and permanently deactivate pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, and PLP-dependent enzymes. PLP is required for the function of over 300 enzymes and proteins. Virtually every major system in the body is impacted directly or indirectly by PLP. The administration of carbidopa and benserazide potentially induces a nutritional catastrophe. During the first 15 years of prescribing L-dopa, a decreasing Parkinson's disease death rate was observed. Then, in 1976, 1 year after US Food and Drug Administration approved the original L-dopa/carbidopa combination drug, the Parkinson's disease death rate started increasing. This trend has continued to the present, for 38 years and counting. The previous literature documents this increasing death rate, but no hypothesis has been offered concerning this trend. Carbidopa is postulated to contribute to the increasing Parkinson's disease death rate and to the classification of Parkinson's as a progressive neurodegenerative disease. It may contribute to L-dopa tachyphylaxis.

Keywords: L-dopa, levodopa, vitamin B6, pyridoxal 5'-phosphate.

Administration of supplemental L-tyrosine with phenelzine: a clinical literature review
Clinical Pharmacology: Advances and Applications
Dove Press open access
July 2014

Abstract: The subject of this literature review is the alleged relationship between L-tyrosine, phenelzine, and hypertensive crisis. Phenelzine (Nardil®) prescribing information notes: “The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises (see WARNINGS). Therefore, patients being treated with NARDIL should not take […] L-tyrosine […]”. Interest in the scientific foundation of this claim was generated during routine patient care. A comprehensive literature search of Google Scholar and PubMed revealed no reported cases of hypertensive crisis associated with concomitant administration of L-tyrosine and phenelzine. Review of current US Food and Drug Administration nutritional guidelines relating to ongoing phenelzine studies reveals no mention and requires no consideration of L-tyrosine ingestion in combination with phenelzine. This paper is intended to provide an objective review of the science to then allow the reader to formulate the final opinion.

Keywords: hypertensive crisis, phenelzine, tyrosine, tyramine, stroke, phenelzine.

Management of L-dopa overdose in the competitive inhibition state
Drug, Healthcare and Patient Safety, Volume 6
Dove Press open access
July 2014

Abstract: The amino acid L-3,4-dihydroxyphenylalanine (L-dopa) is prescribed for conditions where increased central and/or peripheral dopamine synthesis is desired. Its administration can establish dopamine concentrations higher than can be achieved from an optimal diet. Specific indications include Parkinson's disease and restless leg syndrome. The interaction between serotonin and dopamine exists in one of two distinctly different physiologic states: the endogenous state or the competitive inhibition state. Management with L-dopa in the competitive inhibition state is the focus of this paper. In the past, control of the competitive inhibition state was thought to be so difficult and complex that it was described in the literature as functionally “meaningless”. When administering L-dopa without simultaneous administration of serotonin precursors, the patient is in the endogenous state. Experience gained with patient outcomes during endogenous L-dopa administration does not allow predictability of L-dopa outcomes in the competitive inhibition state. The endogenous approach typically increases the daily L-dopa dosing value in a linear fashion until symptoms of Parkinson's disease are under control. It is the novel observations made during treatment with the competitive inhibition state approach that L-dopa dosing values above or below the optimal therapeutic range are generally associated with the presence of the exact same Parkinson's disease symptoms with identical intensity. This recognition requires a novel approach to optimization of daily L-dopa dosing values from that used in the endogenous state. This paper outlines that novel approach through utilization of a pill stop. This approach enhances patient safety through its ability to prevent L-dopa overdose, while assisting in the establishment of the optimal therapeutic L-dopa daily dosing value.

Keywords: L-3,4-dihydroxyphenylalanine, L-dopa, levodopa, Parkinson's disease

5-HTP efficacy and contraindications
Neuropsychiatric Disease and Treatment
Dove Press open access
July 2012

Abstract: L-5-hydroxytryptophan (5-HTP) is the immediate precursor of serotonin. It is readily synthesized into serotonin without biochemical feedback. This nutrient has a large and strong following who advocate exaggerated and inaccurate claims relating to its effectiveness in the treatment of depression and a number of other serotonin-related diseases. These assertions are not supported by the science. Under close examination, 5-HTP may be contraindicated for depression in some of the very patients for whom promoters of 5-HTP advocate its use.

Relative nutritional deficiencies associated with centrally acting monoamines
International Journal of General Medicine
Dove Press open access
May 2012

Abstract: Two primary categories of nutritional deficiency exist. An absolute nutritional deficiency occurs when nutrient intake is not sufficient to meet the normal needs of the system, and a relative nutritional deficiency exists when nutrient intake and systemic levels of nutrients are normal, while a change occurs in the system that induces a nutrient intake requirement that cannot be supplied from diet alone. The purpose of this paper is to demonstrate that the primary component of chronic centrally acting monoamine (serotonin, dopamine, norepinephrine, and epinephrine) disease is a relative nutritional deficiency induced by postsynaptic neuron damage..

The discrediting of the monoamine hypothesis
International Journal of General Medicine
Dove Press open access
February 2012

Abstract: The monoamine hypothesis has been recognized for over half a century as a reference point to understanding electrical dysfunction associated with disease states, and/or regulatory dysfunction related to synaptic, centrally acting monoamine concentrations (serotonin, dopamine, norepinephrine, and epinephrine).

Monoamine depletion by reuptake inhibitors
Drug, Healthcare and Patient Safety
Dove Press open access
October 2011

Abstract: Disagreement exists regarding the etiology of cessation of the observed clinical results with administration of reuptake inhibitors. Traditionally, when drug effects wane, it is known as tachyphylaxis. With reuptake inhibitors, the placebo effect is significantly greater than the drug effect in the treatment of depression and attention deficit hyperactivity disorder, leading some to assert that waning of drug effects is placebo relapse, not tachyphylaxis.

APRESS: apical regulatory super system, serotonin, and dopamine interaction
Neuropsychiatric Disease and Treatment
Dove Press open access
August 4, 2011

Abstract: The most significant aspect of this paper is the documentation of newly recognized relationships between serotonin and dopamine. When transport of serotonin and dopamine are both in the competitive inhibition state, manipulation of the concentrations of one will lead to predictable changes in concentrations of the other. From a functional standpoint, processes regulated and controlled by changes to only serotonin can now be controlled by changes to dopamine, and vice versa, in a predictable manner.

Validity of urinary monoamine assay sales under the “spot baseline urinary neurotransmitter testing marketing model”
International Journal of Nephrology and Renovascular Disease
Dove Press open access
July 2011, Volume 2011:4

Abstract: Spot baseline urinary monoamine assays have been used in medicine for over 50 years as a screening test for monoamine-secreting tumors, such as pheochromocytoma and carcinoid syndrome. In these disease states, when the result of a spot baseline monoamine assay is above the specific value set by the laboratory, it is an indication to obtain a 24-hour urine sample to make a definitive diagnosis. There are no defined applications where spot baseline urinary monoamine assays can be used to diagnose disease or other states directly. No peer-reviewed published original research exists which demonstrates that these assays are valid in the treatment of individual patients in the clinical setting. Since 2001, urinary monoamine assay sales have been promoted for numerous applications under the “spot baseline urinary neurotransmitter testing marketing model”. There is no published peer-reviewed original research that defines the scientific foundation upon which the claims for these assays are made. On the contrary, several articles have been published that discredit various aspects of the model. To fill the void, this manuscript is a comprehensive review of the scientific foundation and claims put forth by laboratories selling urinary monoamine assays under the spot baseline urinary neurotransmitter testing marketing model.

Microperforation Prolotherapy™: a novel method for successful nonsurgical treatment of atraumatic spontaneous anterior sternoclavicular subluxation with an illustrative case
Journal of Sports Medicine
Dove Press open access
June 2011 , Volume 2011

Abstract: Surgical repair of an atraumatic spontaneous anterior subluxation of the sternoclavicular joint (herein referred to as the “SCJ”) is often associated with poor outcome expectations. With traditional treatment, successful conservative therapy usually incorporates major lifestyle alterations. This manuscript discusses a novel approach known as "microperforation prolotherapy."™ To illustrate the technique, the care of a patient who benefitted from this treatment is reviewed.

The dual-gate lumen model of renal monoamine transport
Neuropsychiatric Disease and Treatment
July 2, 2010

Abstract: The three-phase response of urinary serotonin and dopamine in subjects simultaneously taking amino acid precursors of serotonin and dopamine has been defined. No model exists regarding the renal etiology of the three-phase response.

This writing outlines a model explaining the origin of the three-phase response of urinary serotonin and dopamine. A “dual-gate lumen transporter model” for the basolateral monoamine transporters of the kidneys is proposed as being the etiology of the three-phase urinary serotonin and dopamine responses.

Amino Acid Responsive Crohn’s Disease: a case study

Clinical and Experimental Gastroenterology
December 6, 2010

Abstract: This writing discusses a case study of a 37-year-old white male with a 22 year history of progressive and severe Crohn’s disease, with no previous remissions, that showed dramatic and relatively abrupt remission of symptoms when a novel treatment approach was prescribed.

This treatment protocol involved the balancing of serotonin and dopamine through the organic cation transporters (OCT) with the guidance of OCT analysis interpretation.

Neurotransmitter testing of the urine: a comprehensive analysis
Journal of Urology
Dove Press open access
October 6, 2010

Abstract: This paper analyzes the statistical correlation of urinary serotonin and dopamine data in subjects not suffering from monoamine-secreting tumors such as pheochromocytoma or carcinoid syndrome. Peer-reviewed literature and statistical analyses were searched and monoamine (serotonin and dopamine) assays defined in order to facilitate their proper interpretation. Many research findings in the literature are novel. Baseline assays completed with no monoamine precursors differ from baseline assays performed on a different day in the same subject. There is currently no scientific basis, value, or predictability in obtaining baseline monoamine assays. Urinary assays performed while taking precursors can demonstrate a lack of correlation or unexpected correlations such as inverse relationships. The only valid model for interpretation of urinary monoamine assays is the “three-phase model” which leads to predictability between monoamine assays and precursor administration in varied amounts.

ADHD Study: Treatment with Amino Acids
Neuropsychiatric Disease and Treatment
January 25, 2011

85 children with ADHD treated with amino amino acids and OCT assay interpretation with results that appear superior to prescription ADHD drugs.

Treatment of Parkinson's Disease
International Journal of General Medicine
January 18, 2011

L-dopa holds the highest potential in the treatment of Parkinson disease. Its potential is limited by mis-management of amino acids and use of carbidopa. This paper outlines proper management of L-dopa in the treatment of Parkinson disease.

Differentiating Garden Variety Depression from Bipolar Depression with Amino Acids
Neuropsychiatric Disease and Treatment
November 9, 2010

Differentiating depressive dominant bipolar disorder from garden variety depression with amino acids guided by OCT assay interpretation.

The Urinary Neurotransmitter Testing Model Discredited - Part One
Open Access Journal of Urology
October 6, 2010

The peer-reviewed scientific paper that exposed and discredited
the "urinary neurotransmitter testing model."

The Urinary Neurotransmitter Testing Model Discredited - Part Two
Open Access Journal of Urology
February 3, 2011

A second paper discrediting the "urinary neurotransmitter testing model."