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Hinz M, Stein A, Uncini T. Int J Nephrol Renovasc Dis. 2011;4:101–113.The Editor-in-chief and Publisher of International Journal of Nephrology and Renovascular Disease wish to retract the published article.This review article cites several original research articles published by the authors, which have recently been retracted. This article draws on the findings from those original research articles to form central arguments and discussion, and as a result of the research articles’ retraction, the argument presented in this article is no longer valid and the editor has determined it should be retracted.Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Uncini T. Neuropsychiatr Dis Treat. 2012;8:323–328.The Editor-in-chief and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article.This review article cites several original research articles published by the authors, which have recently been retracted. This article draws on the findings from those original research articles to form central arguments and discussion, and as a result of the research articles’ retraction, the argument presented in this article is no longer valid and the editor has determined it should be retracted.Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.This retraction relates to this paper

Hinz M, Stein A, Uncini T. Int J Gen Med. 2012;5:413– 430. The Editor-in-chief and Publisher of International Journal of General Medicine wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.This retraction relates to this paperThis retraction relates to this Corrigendum

Hinz M, Stein A, Uncini T. Neuropsychiatr Dis Treat. 2010;6:387–392. The Editor-in-chief and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it as determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Stein A, Hinz M, Uncini T. Clin Exp Gastroenterol. 2010;3:171–177. The Editor-in-chief and Publisher of Clinical and Experimental Gastroenterology wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the requested IRB and consent to publish information relating to this study and it was determined the study did not meet the ethical publication requirements for research involving human subjects. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Uncini T. Int J Gen Med. 2012;5:135–142. The Editor-in-chief and Publisher of International Journal of General Medicine wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Uncini T. Neuropsychiatr Dis Treat. 2010;6:741—747. The Editor-in-chief and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Uncini T. Drug Healthc Patient Saf. 2011;3:69–77. The Editor-in-chief and Publisher of Drug, Healthcare and Patient Safety wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Neff R, Weinberg R, Uncini T. Neuropsychiatr Dis Treat. 2011;7:31–38. The Editor-in-chief and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Trachte G, Uncini T, Hinz M. Neuropsychiatr Dis Treat. 2009;5:227–235. The Editor-in-chief and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Trachte G, Uncini T. Res Rep Urol. 2010;2:177–183. The Editor-in-chief and Publisher of Research and Reports in Urology wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Uncini T. Neuropsychiatr Dis Treat. 2011;7:457–463. The Editor-in-chief and Publisher of Neuropsychiatric Disease and Treatment wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.This retraction relates to this paper

Hinz M, Stein A, Uncini T. Res Rep Urol. 2011;3:19–24. The Editor-in-chief and Publisher of Research and Reports in Urology wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the required IRB and informed consent information relating to this study and it was determined the study did not meet the standard ethical publication requirements for studies involving human subjects in research. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the required study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Uncini T. Int J Gen Med. 2011;4:165– 174. The Editor-in-chief and Publisher of International Journal of General Medicine wish to retract the published article. Following the conclusion of our investigation the decision has been made to retract the published article. The authors did not provide the requested IRB and consent to publish information relating to this study and it was determined the study did not meet the ethical publication requirements for research involving human subjects. These requirements are based on guidelines issued by the World Medical Association and the International Committee of Medical Journal Editors. Additionally, the authors did not provide the study protocols, raw data and other study documents relating to this study as requested. Given our concerns about the standard of research ethics, competing interests and that the authors have not supplied the information we requested to verify and validate the reported findings, the editor has determined the article should be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hinz M, Stein A, Uncini T. Neuropsychiatr Dis Treat. 2011;7:457–463. The Editor-in-Chief and Publisher of Neuropsychiatric Disease and Treatment wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. Neuropsychiatric Disease and Treatment would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation.Read the original article

Hinz M, Stein A, Neff R,Weinberg R, Uncini T. Neuropsych Dis Treat. 2011;7:31–38. The Editor-in-Chief and Publisher of Neuropsychiatric Disease and Treatment wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. Neuropsychiatric Disease and Treatment would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Uncini T. Int J Gen Med. 2012;5:135–142. The Editor-in-Chief and Publisher of International Journal of General Medicine wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. International Journal of General Medicine would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Uncini T. Neuropsychiatr Dis Treat. 2010;6:741–747. The Editor-in-Chief and Publisher of Neuropsychiatric Disease and Treatment wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. Neuropsychiatric Disease and Treatment would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Trachte G, Uncini T, Hinz M. Neuropsychiatr Dis Treat. 2009;5:227– 235. The Editor-in-Chief and Publisher of Neuropsychiatric Disease and Treatment wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. Neuropsychiatric Disease and Treatment would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Uncini T. Neuropsych Dis Treat. 2010;6:387–392. The Editor-in-Chief and Publisher of Neuropsychiatric Disease and Treatment wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. Neuropsychiatric Disease and Treatment would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Uncini T. Neuropsychiatr Dis Treat. 2012;8:323– 328. The Editor-in-Chief and Publisher of Neuropsychiatric Disease and Treatment wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors and alleged excessive self-citation for the published article. Neuropsychiatric Disease and Treatment would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Uncini T. Drug Healthc Patient Saf. 2011;3:69–77. The Editor-in-Chief and Publisher of Drug, Healthcare and Patient Safety wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. Drug, Healthcare and Patient Safety would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Uncini T. Res Rep Urol. 2011;3:19–24. The Editor-in-Chief and Publisher of Research and Reports in Urology (formerly Open Access Journal of Urology) wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. Research and Reports in Urology would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Trachte G, Uncini T. Res Rep Urol. 2010;2:177–183. The Editor-in-Chief and Publisher of Research and Reports in Urology (formerly Open Access Journal of Urology) wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. Research and Reports in Urology would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Stein A, Hinz M, Uncini T. Clin Exp Gastroenterol. 2010;3:171– 177. The Editor-in-Chief and Publisher of Clinical and Experimental Gastroenterology wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology and study data for the published article. Clinical and Experimental Gastroenterologywould like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation.Read the original article

Hinz M, Stein A, Uncini T. Int J Gen Med. 2012;5:413–430. The Editor-in-Chief and Publisher of International Journal of General Medicine wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article.International Journal of General Medicine would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Uncini T. Int J Nephrol Renovasc Dis. 2011;4:101–113. The Editor-in-Chief and Publisher of International Journal of Nephrology and Renovascular Disease wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors for the published article. International Journal of Nephrology and Renovascular Disease would like to alert readers of this while our investigation is still ongoing and we will provide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Hinz M, Stein A, Uncini T. Int J Gen Med. 2011;4:165–174. The Editor-in-Chief and Publisher of International Journal of General Medicine wish to issue an Expression of Concern for the published article. Concerns have been raised regarding the alleged undisclosed competing interests of some of the authors, and the level of information provided on methodology, study data and process of institutional ethical approval for the published article. International Journal of General Medicine would like to alert readers of this while our investigation is still ongoing and we willprovide an update following the conclusion of our investigation. The authors have been informed of these concerns and of our investigation. Read the original article

Marty Hinz,1 Alvin Stein,2 Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc, Cape Coral, 2Stein Orthopedic Associates, Plantation, FL, USA; 3University Medical Center Mesabi Hibbing, MN, USAAbstract: 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.Keywords: 5-HTP, 5-hydroxytryptophan, L-5-HTP, L-5-hydroxytryptophan

Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics Inc, Cape Coral, 2Stein Orthopedic Associates, Plantation, FL, 3DBS Labs, Duluth, MN, USABackground: 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.Materials and methods: Monoamine transporter optimization results were investigated, re-evaluated, and correlated with previous publications by the authors under the relative nutritional deficiency hypothesis. Most of those previous publications did not discuss the concept of a relative nutritional deficiency. It is the purpose of this paper to redefine the etiology expressed in these previous writings into the realm of relative nutritional deficiency, as demonstrated by monoamine transporter optimization. The novel and broad range of amino acid precursor dosing values required to address centrally acting monoamine relative nutritional deficiency properly is also discussed.Results: Four primary etiologies are described for postsynaptic neuron damage leading to a centrally acting monoamine relative nutritional deficiency, all of which require monoamine transporter optimization to define the proper amino acid dosing values of serotonin and dopamine precursors.Conclusion: Humans suffering from chronic centrally acting monoamine-related disease are not suffering from a drug deficiency; they are suffering from a relative nutritional deficiency involving serotonin and dopamine amino acid precursors. Whenever low or inadequate levels of monoamine neurotransmitters exist, a relative nutritional deficiency is present. These precursors must be administered simultaneously under the guidance of monoamine transporter optimization in order to achieve optimal relative nutritional deficiency management. Improper administration of these precursors can exacerbate and/or facilitate new onset of centrally acting monoamine-related relative nutritional deficiencies.Keywords: nutritional deficiency, serotonin, dopamine, monoamine

Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc, Cape Coral, FL, 2Stein Orthopedic Associates, Plantation, FL, 3Fairview University Medical Center, Hibbing, MN, USABackground: 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).Methods: Organic cation transporters (OCT) are a primary force controlling intracellular and extracellular (including synaptic) concentrations of centrally acting monoamines and their amino acid precursors. A new type of research was analyzed in this paper (previously published by the authors) relating to determining the functional status of the nutritionally driven organic cation transporters. It was correlated with the claims of the monoamine hypothesis.Results: Results of laboratory assays from subjects not suffering from a hyperexcreting tumor show that centrally acting monoamine concentrations are indistinguishable in subjects with and without disease symptoms and/or regulatory dysfunction. Analysis of centrally acting monoamine concentrations in the endogenous state reveals a significant difference in day-to-day assays performed on the same subject with and without monoamine-related disease symptoms and/or regulatory dysfunction. The day-to-day difference renders baseline testing in the endogenous state non-reproducible in the same subject.Conclusion: It is asserted that the monoamine hypothesis, which claims that low synaptic levels of monoamines are a primary etiology of disease, is not a valid primary reference point for understanding chronic electrical dysfunction related to the centrally acting monoamines. Furthermore, the "bundle damage theory" is a more accurate primary model for understanding chronic dysfunction. The "bundle damage theory" advocates that synaptic monoamine levels are normal but not adequate in states associated with chronic electrical dysfunction and that levels need to be increased to compensate for the chronic postsynaptic electrical dysfunction due to existing damage. The monoamine hypothesis, in failing to accurately explain the etiology of chronic neuronal electrical flow dysfunction in the endogenous state, is reduced to no more than a historical footnote.Keywords: monoamine hypothesis, monoamine theory, serotonin, dopamine, neuronal dysfunction, bundle damage theory

Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics Inc, Cape Coral, FL; 2Stein Orthopedic Associates, Plantation, FL; 3DBS Labs Inc, Duluth, MN, USABackground: 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.Methods: Two groups were retrospectively evaluated. Group 1 was composed of subjects with depression and Group 2 was composed of bariatric subjects treated with reuptake inhibitors for appetite suppression.Results: In Group 1, 200 subjects with depression were treated with citalopram 20 mg per day. A total of 46.5% (n = 93) achieved relief of symptoms (Hamilton-D rating score ≤ 7), of whom 37 (39.8%) of whom experienced recurrence of depression symptoms, at which point an amino acid precursor formula was started. Within 1–5 days, 97.3% (n = 36) experienced relief of depression symptoms. In Group 2, 220 subjects were treated with phentermine 30 mg in the morning and citalopram 20 mg at 4 pm. In this group, 90.0% (n = 198) achieved adequate appetite suppression. The appetite suppression ceased in all 198 subjects within 4–48 days. Administration of an amino acid precursor formula restored appetite suppression in 98.5% (n = 195) of subjects within 1–5 days.Conclusion: Reuptake inhibitors do not increase the total number of monoamine molecules in the central nervous system. Their mechanism of action facilitates redistribution of monoamines from one place to another. In the process, conditions are induced that facilitate depletion of monoamines. The "reuptake inhibitor monoamine depletion theory" of this paper offers a novel and unified explanation for the waning of response seen after a reuptake inhibitor is started, independent of a drug or placebo etiology.Keywords: reuptake inhibitor, depletion, tachyphylaxis, relapse, serotonin, dopamine

Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc, Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3DBS Labs, Duluth, MN, USABackground: The monoamines serotonin and dopamine are known to exist in two separate states: the endogenous state and the competitive inhibition state. The presence of the competitive inhibition state has been known to science for many years, but from a functional standpoint it has been noted in the literature as being "meaningless."Methods: A large database of monoamine transporter response to amino acid precursor administration variations with clinical outcomes was accumulated. In the process, a new organic cation transporter (OCT) model has been published, and OCT functional status determination along with amino acid precursor manipulation methods have been invented and refined.Results: Methodology was developed whereby manipulation of the OCT, in the competitive inhibition state, is carried out in a predictable manner. This, in turn, has disproved the long-held assertion that the monoamine competitive inhibition state is functionally meaningless.Conclusion: 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.Keywords: catecholamine, monoamine, competitive inhibition state

Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, Neuro Research Clinics Inc, Cape Coral, FL; 2Stein Orthopedic Associates, Plantation, FL; 3Laboratory, Fairview Regional Medical Center-Mesabi, Hibbing, MN, USAAbstract: 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.Keywords: monoamine, serotonin, dopamine, norepinephrine, epinephrine, urine, urinary

Hinz M, Stein A, Uncini T. Int J Gen Med. 2011:4 165–174 On page 173, Disclosure section, “MH discloses ownership of DBS Labs, Duluth, MN, USA. TU discloses directorship of DBS Labs, Duluth, MN, USA. AS reports no conflicts of interest in this work.” should have read “MH discloses his relationship with West Duluth Distribution Company which terminated June 2011 and ownership of DBS Labs, Duluth, MN, USA. TU discloses directorship of DBS Labs, Duluth, MN, USA. AS reports no conflicts of interest in this work.”Read the original article.

CorrigendumHinz M, Stein A, Uncini T. Int J Gen Med. 2012;5:413–430. On page 428, Disclosure section, “The authors report no conflicts of interest in this work.” should have read “MH discloses his relationship with West Duluth Distribution Company which terminated June 2011. The other authors report no conflicts of interest in this work”.Read the original paper by Hinz et al.

Background: 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)., Methods: Organic cation transporters (OCT) are a primary force controlling intracellular and extracellular (including synaptic) concentrations of centrally acting monoamines and their amino acid precursors. A new type of research was analyzed in this paper (previously published by the authors) relating to determining the functional status of the nutritionally driven organic cation transporters. It was correlated with the claims of the monoamine hypothesis., Results: Results of laboratory assays from subjects not suffering from a hyperexcreting tumor show that centrally acting monoamine concentrations are indistinguishable in subjects with and without disease symptoms and/or regulatory dysfunction. Analysis of centrally acting monoamine concentrations in the endogenous state reveals a significant difference in day-to-day assays performed on the same subject with and without monoamine-related disease symptoms and/or regulatory dysfunction. The day-to-day difference renders baseline testing in the endogenous state non-reproducible in the same subject., Conclusion: It is asserted that the monoamine hypothesis, which claims that low synaptic levels of monoamines are a primary etiology of disease, is not a valid primary reference point for understanding chronic electrical dysfunction related to the centrally acting monoamines. Furthermore, the "bundle damage theory" is a more accurate primary model for understanding chronic dysfunction. The "bundle damage theory" advocates that synaptic monoamine levels are normal but not adequate in states associated with chronic electrical dysfunction and that levels need to be increased to compensate for the chronic postsynaptic electrical dysfunction due to existing damage. The monoamine hypothesis, in failing to accurately explain the etiology of chronic neuronal electrical flow dysfunction in the endogenous state, is reduced to no more than a historical footnote.

Unlabelled: An extensive list of side effects and problems are associated with the administration of l-dopa (l-3, 4-dihydroxyphenylalanine) during treatment of Parkinson's disease. These problems can preclude achieving an optimal response with l-dopa treatment., Purpose: To present a case study outlining a novel approach for the treatment of Parkinson's disease that allows for management of problems associated with l-dopa administration and discusses the scientific basis for this treatment., Patients and Methods: The case study was selected from a database containing 254 Parkinson's patients treated in developing and refining this novel approach to its current state. The spectrum of patients comprising this database range from newly diagnosed, with no previous treatment, to those who were diagnosed more than 20 years before and had virtually exhausted all medical treatment options. Parkinson's disease is associated with depletion of tyrosine hydroxylase, dopamine, serotonin, and norepinephrine. Exacerbating this is the fact that administration of l-dopa may deplete l-tyrosine, l-tryptophan, 5-hydroxytryptophan (5-HTP), serotonin, and sulfur amino acids. The properly balanced administration of l-dopa in conjunction with 5-HTP, l-tyrosine, l-cysteine, and cofactors under the guidance of organic cation transporter functional status determination (herein referred to as "OCT assay interpretation") of urinary serotonin and dopamine, is at the heart of this novel treatment protocol., Results: When 5-HTP and l-dopa are administered in proper balance along with l-tyrosine, l-cysteine, and cofactors under the guidance of OCT assay interpretation, the long list of problems that can interfere with optimum administration of l-dopa becomes controllable and manageable or does not occur at all. Patient treatment then becomes more effective by allowing the implementation of the optimal dosing levels of l-dopa needed for the relief of symptoms without the dosing value barriers imposed by side effects and adverse reactions seen in the past.

Background: The purpose of this paper is to present the results of statistical analysis of spot baseline urinary norepinephrine and epinephrine assays in correlation with spot baseline urinary serotonin and dopamine findings previously published by the authors. Our research indicates a need for physicians and decision-makers to understand the lack of validity of this type of spot baseline monoamine testing when using it in the decision-making process for neurotransmitter deficiency disorders., Methods: Matched-pairs t-tests were performed for a group of subjects for whom spot baseline urinary norepinephrine and epinephrine assays were performed on samples collected on different days then paired by subject., Results: The reported laboratory test results for urinary serotonin, dopamine, norepinephrine, and epinephrine, obtained on different days from the same subjects, differed significantly and were not reproducible., Conclusion: Spot baseline monoamine assays, in subjects not suffering from a monoamine-secreting tumor, such as pheochromocytoma or carcinoid syndrome, are of no value in decision-making due to this day-to-day variability and lack of reproducibility. While there have been attempts to integrate spot baseline urinary monoamine assays into treatment of peripheral or central neurotransmitter-associated disease states, diagnosis of neurotransmitter imbalances, and biomarker applications, significant differences in day-to-day reproducibility make this impossible given the known science as it exists today.

Background: This paper documents a retrospective pilot study of a novel approach for treating attention deficit hyperactivity disorder (ADHD) with amino acid precursors of serotonin and dopamine in conjunction with urinary monoamine assays subjected to organic cation transporter (OCT) functional status determination. The goal of this research was to document the findings and related considerations of a retrospective chart review study designed to identify issues and areas of concern that will define parameters for a prospective controlled study., Methods: This study included 85 patients, aged 4-18 years, who were treated with a novel amino acid precursor protocol. Their clinical course during the first 8-10 weeks of treatment was analyzed retrospectively. The study team consisted of PhD clinical psychologists, individuals compiling clinical data from records, and a statistician. The patients had been treated with a predefined protocol for administering amino acid precursors of serotonin and dopamine, along with OCT assay interpretation as indicated., Results: In total, 67% of participants achieved significant improvement with only amino acid precursors of serotonin and dopamine. In patients who achieved no significant relief of symptoms with only amino acid precursors, OCT assay interpretation was utilized. In this subgroup, 30.3% achieved significant relief following two or three urine assays and dosage changes as recommended by the assay results. The total percentage of patients showing significant improvement was 77%., Conclusion: The efficacy of this novel protocol appears superior to some ADHD prescription drugs, and therefore indicates a need for further studies to verify this observation. The findings of this study justify initiation of further prospective controlled studies in order to evaluate more formally the observed benefits of this novel approach in the treatment of ADHD.

Purpose: A novel method for differentiating and treating bipolar disorder cycling on the depressive pole from patients who are suffering a major depressive episode is explored in this work. To confirm the diagnosis of type 1 or type 2 bipolar disorder, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria require that at least one manic or hypomanic episode be identified. History of one or more manic or hypomanic episodes may be impossible to obtain, representing a potential blind spot in the DSM-IV diagnostic criteria. Many bipolar patients who cycle primarily on the depressive side for many years carry a misdiagnosis of recurrent major depression, leading to treatment with antidepressants that achieve little or no relief of symptoms. This article discusses a novel approach for diagnosing and treating patients with bipolar disorder cycling on the depressive pole versus patients with recurrent major depression., Patients and Methods: Patients involved in this study were formally diagnosed with recurrent major depression under DSM-IV criteria and had no medical history of mania or hypomania to support the diagnosis of bipolar disorder. All patients had suffered multiple depression treatment failures in the past, when evaluated under DSM-IV guidelines, secondary to administration of antidepressant drugs and/or serotonin with dopamine amino acid precursors., Results: This study contained 1600 patients who were diagnosed with recurrent major depression under the DSM-IV criteria. All patients had no medical history of mania or hypomania. All patients experienced no relief of depression symptoms on level 3 amino acid dosing values of the amino acid precursor dosing protocol. Of 1600 patients studied, 117 (7.3%) nonresponder patients were identified who experienced no relief of depression symptoms when the serotonin and dopamine amino acid precursor dosing values were adjusted to establish urinary serotonin and urinary dopamine levels in the Phase III therapeutic ranges. All of the 117 nonresponders who achieved no relief of depression symptoms were continued on this amino acid dosing value, and a mood-stabilizing drug was started. At this point, complete relief of depression symptoms, under evaluation with DSM-IV criteria, was noted in 114 patients within 1-5 days. With further dose adjustment of the mood-stabilizing drug, the remaining three nonresponders achieved relief of depression symptoms., Conclusion: Resolution of depression symptoms with the addition of a mood-stabilizing drug in combination with proper levels of serotonin and dopamine amino acid precursors was the basis for a clinical diagnosis of bipolar disorder cycling on the depressive pole.

Unlabelled: 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., Purpose: This paper reviews the basic science of urinary monoamine assays. Results of statistical analysis correlating baseline and nonbaseline assays are reported and provide valid methods for interpretation of urinary serotonin and dopamine results., Patients and Methods: Key scientific claims promoting the validity of the urinary neurotransmitter testing (UNT) model applications are discussed. Many of these claims were not supported by the scientific literature. Matched-pairs t-tests were performed on several groupings. Results of all statistical tests were compared with peer-reviewed literature., Results: The statistical analysis failed to support the UNT model. Peer-reviewed literature search failed to verify scientific clams made in support of applications of the UNT model in many cases.

Unlabelled: The three-phase response of urinary serotonin and dopamine in subjects simultaneously taking amino acid precursors of serotonin and dopamine has been defined.1,2 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., Purpose: The purpose of this writing is to document the internal renal function model that has evolved in research during large-scale assay with phase interpretation of urinary serotonin and dopamine., Patients and Methods: In excess of 75,000 urinary monoamine assays from more than 7,500 patients were analyzed. The serotonin and the dopamine phase were determined for specimens submitted in the competitive inhibition state. The phase determination findings were then correlated with peer-reviewed literature., Results: The correlation between the three-phase response of urinary serotonin and dopamine with internal renal processes of the bilateral monoamine transporter and the apical monoamine transporter of the proximal convoluted renal tubule cells is defined., Conclusion: The phase of urinary serotonin and dopamine is dependent on the status of the serotonin gate, dopamine gate, and lumen of the basolateral monoamine transporter while in the competitive inhibition state.

Purpose: This paper reviews the clinical course of a case of severe Crohn's disease and discusses the scientific ramifications of a novel treatment approach., Patients and Methods: A case study of a 37-year-old male with a 22-year history of Crohn's disease whose clinical course had experienced no sustained remissions. The patient was treated with a protocol that utilized serotonin and dopamine amino acid precursors administered under the guidance of organic cation transporter assay interpretation., Results: Within 5 days of achieving the necessary balance of serotonin and dopamine, the patient experienced remission of symptoms. This remission has been sustained without the use of any Crohn's disease medications., Conclusion: In Crohn's disease, it is known that there is an increase of both synthesis and tissue levels of serotonin in specific locations. It is asserted that this is prima facie evidence of a significant imbalance in the serotonin-dopamine system, leading to serotonin toxicity. The hypothesis formulated is that improperly balanced serotonin and dopamine transport, synthesis, and metabolism is a primary defect contributing to the pathogenesis of Crohn's disease.

Amino acid precursors of dopamine and serotonin have been administered for decades to treat a variety of clinical conditions including depression, anxiety, insomnia, obesity, and a host of other illnesses. Dietary administration of these amino acids is designed to increase dopamine and serotonin levels within the body, particularly the brain. Convincing evidence exists that these precursors normally elevate dopamine and serotonin levels within critical brain tissues and other organs. However, their effects on urinary excretion of neurotransmitters are described in few studies and the results appear equivocal. The purpose of this study was to define, as precisely as possible, the influence of both 5-hydroxytryptophan (5-HTP) and tyrosine on urinary excretion of serotonin and dopamine in a large human population consuming both 5-HTP and tyrosine. Curiously, only 5-HTP exhibited a marginal stimulatory influence on urinary serotonin excretion when 5-HTP doses were compared to urinary serotonin excretion; however, a robust relationship was observed when alterations in 5-HTP dose were compared to alterations in urinary serotonin excretion in individual patients. The data indicate three statistically discernible components to 5-HTP responses, including inverse, direct, and no relationships between urinary serotonin excretion and 5-HTP doses. The response to tyrosine was more consistent but primarily yielded an unexpected reduction in urinary dopamine excretion. These data indicate that the urinary excretion pattern of neurotransmitters after consumption of their precursors is far more complex than previously appreciated. These data on urinary neurotransmitter excretion might be relevant to understanding the effects of the precursors in other organs.