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Treatment of Pyroluric Schizophrenia (Malvaria) With Large Doses of Pyridoxine and a Dietary Supplement of Zinc
Abstract
A syndrome is described in the mauve-positive, urinary kryptopyrrole-ex-creting patient which has many distinguishing features, namely: (1) white spots in nails; (2) failure to remember dreams; (3) sweetish breath odor; (4) left upper quadrant abdominal pain; (5) dysperceptive schizophrenia and neurological-metabolical symptoms. These patients excrete urinary pyrroles at a level above 20 mcg percent. The usual age of onset is 15 to 20 years of age when the patient encounters the stress of senior year high school or first year of college. Kryptopyrrole has been shown to combine chemically with pyridoxal which then complexes with zinc to produce symptoms of vitamin B6 and zinc deficiency. The incidence is 30 to 40 percent in schizophrenics and 5 to 10 percent in normals. The disorder is familial and is responsible for the high incidence of "schizophrenia" in families. Adequate doses of 86 (up to 3.0 gm/day) and zinc will relieve the symptoms and reduce the urinary excretion of kryptopyrrole to the normal range. Discontinuation of the B6 -zinc results in a rapid return of serious symptoms within 48 hours. Work is progressing on the biochemical nature of stress-induced formation of kryptopyrrole.
... It has been suggested that zinc (likely as Zn 2+ ) is excreted as a pyridoxal phosphate kryptopyrrole chelate 46 (FIGURE 5). This might be a mechanism of Zn 2+ depletion, resulting in reduced serum Zn 2+ concentration, with its concomitant implications for GABA-mediated neurotransmission and perhaps its role in anxiety. ...
... It is interesting to speculate that kryptopyrrole has its biochemical origins in stercobilin and might indicate a link with leaky gut syndrome, which has been reported to be associated with anxiety. 50 If kryptopyrrole is excreted in urine in clinical anxiety, the postulated co-chelate with pyridoxal phosphate and zinc 46 would suggest a biochemical mechanism of anxiety, point to a dietary supplement-based treatment, and present a biomarker for diagnosis; however, because there is no pyrrole concentration difference between control and anxious urine samples in this small sample set, more work is needed to assess the usefulness of kryptopyrrole as an anxiety biomarker. ...
... This clearly shows that HPL does not react with 4-dimethylaminobenzaldehyde (DMAB) and that kryptopyrrole reacts in a concentration-related manner. Results are shown as mean ± SD (Postulated structure of the pyridoxal phosphate/kryptopyrrole-zinc chelate46 (left) and possible, but unlikely, zinckryptopyrrole complex (right).Downloaded from https://academic.oup.com/labmed/advance-article/doi/10.1093/labmed/lmad086/7271490 by guest on 13 September 2023 ...
Objective
For over 60 years there has been conjecture about the identity of an Ehrlich’s test positive pyrrole (Mauve Factor) reputed to be a biomarker for psychological disorders, including anxiety. We reviewed studies that attempt to identify Mauve Factor and subjected authentic standards of the 2 main candidates, kryptopyrrole and hydroxypyrrole, to the Ehrlich’s reaction.
Methods
Modified Ehrlich’s test for kryptopyrrole and hydroxypyrrole were applied to urine samples from 10 volunteers, anxious and nonanxious.
Results
Based on the mechanistic chemistry of Ehrlich’s reaction and reactions of the 2 compounds, Mauve Factor cannot be hydroxypyrrole. Analyses of urine samples from volunteers, identified by the Generalized Anxiety Disorder - 7 item scale (GAD-7 ≥10; n = 5) and control urine samples (GAD-7 <10; n = 5) using a kryptopyrrole calibration graph, show that concentrations are similar in both groups.
Conclusion
Kryptopyrrole may be the elusive Mauve Factor. Its possible origin from stercobilin via gut microbiome–mediated metabolism, its link to gut-mediated neurological effects via γ-aminobutyric acid (GABA) receptors, and its predicted interaction with Zn2+ and consequent impact on zinc homeostasis are discussed. The GAD-7 scale does not differentiate between state and trait anxiety and as such, the minimal difference in pyrrole levels between volunteer groups requires further study.
... This reaction is now understood as the combination of p-N,Ndimethylaminobenzaldehyde (DMAB) with the pyrrole moiety ( Figure 1). Pyrroles (a class of five-membered nitrogen containing heterocycles) can be found as chemical sub-units in porphyrin systems such as vitamin B 12 , bile pigments (biliverdin and bilirubin), haem, and chlorophylls [3]. ...
... As reviewed by Warren et al. (2021), numerous studies have attempted to correlate elevated pyrrole levels with the diagnosis of psychiatric disorders but have had limited effect [9]. Unfortunately, most of these studies did not use statistical analyses and/or control group data or had limited sample sizes, which has limited the validity of the data [5,6,[10][11][12][13][14][15][16][17]. Only the Fryar-Williams study followed the "Lambert" method guidelines for collections with results being corrected to creatinine to adjust for hydration [18]. ...
... Based on the previous observations, some researchers have suggested treatments for patients with elevated levels of pyrroles that include supplementation with active B6 and zinc. Clinical trials performed by Pfeiffer et al. first identified this link, demonstrating that supplementation of B6 and zinc led to significant reductions in DMAB-active pyrrole and improvement in patient symptoms [12]. According to clinicians in this field, ongoing treatment of this nature is required to reduce or suppress symptoms [30,31]. ...
Redox imbalance or oxidative stress that results from both environmental and genetic factors is observed in patients with schizophrenia. Therefore, identifying markers of oxidative stress in the early stages of psychosis and using antioxidant treatments as an adjuvant to antipsychotics has important implications. The reaction of p-N,N-dimethylaminobenzaldehyde (DMAB) with pyrrole moieties has been well studied for well over a century for use as a marker of oxidative stress dysregulation. Throughout this time, pyrroles have been investigated with varying veracity in urine extracts to identify elevated levels in patients diagnosed with schizophrenia. Since the 1960’s, various claims have been made with respect to what causes the colour change when DMAB is added to urine extracts. Whilst the substances from this reaction have not been fully elucidated, an objective look at most studies indicates that urobilinogen is likely to be one them. Urobilinogen has also been identified as a major interferent in our results. Both pyrroles and urobilinogen condense the DMAB reaction system (form condensation products) and are quite different. The urobilinogen detected in urine forms when gut microflora chemically reduces the bilirubin content of bile acids. In comparison, evidence suggests that the pyrrole fraction originates from the fragmentation of regulatory haem by reactive oxygen species (ROS) such as hydrogen peroxide and super and nitrous oxides. Clinical studies in our laboratories have established that pyrroles as a urine biomarker have specificity in detecting schizophrenia; however, caution must be applied as the readings are subject to interference by other DMAB active compounds that are present, such as urobilinogen. This review highlights the initial chemistry in isolating pyrroles and provides recommendations for standardised laboratory testing to ensure pyrroles are correctly measured and distinguished from other by-products.
... For example, published clinical guidelines for the management of eUKP suggest use of clinical nutrition supplements containing vitamin B3, B6, and zinc with the intended aim of reducing excretion of urinary kryptopyrroles and improving the health of those with eUKP [2]. The proposed pathophysiology of pyrrole disorder involves the excretion and/or antagonism of vitamin B6 and zinc by way of kryptopyrrole (and assuming HPL) having a physico-chemical affinity for these two nutrients [9], however this mechanism does not appear to have been demonstrated in vivo. The contemporary treatment approach for clinicians subscribing to this proposed pathophysiological process for pyrrole disorder therefore includes supplementation with zinc and vitamin B6, and supporting nutrients such as vitamin C, manganese, biotin, and evening primrose oil [8]. ...
... Plasma zinc and serum copper tests, as well as ceruloplasmin levels, were also reported to be used in the diagnosis of eUKP. The reasoning of their use is likely based on the hypothesis that pyrroles bind zinc in vivo [9], and that copper may antagonise zinc [20]. Plasma zinc is cited to be the measurement of choice in the literature on pyrrole disorder, while there is no mention of genetic tests or pyridoxine [2], which may explain the low reported use of these additional tests. ...
... Mean SD (min, max) postulated that balancing histamine levels may improve symptoms in individuals with schizophrenia [9]. The low reported use of hair mineral tests as an adjunct diagnostic test for eUKP is supported by research showing no difference in hair content of copper, zinc, aluminium and lead in patients with either normal (0-19 mcg/dL) or elevated (≥20 mcg/dL) urinary pyrroles, however patients with elevated urinary pyrroles showed a seven times higher (77 ppm vs 12 ppm) minimum level of zinc in hair samples [20]. ...
Introduction
Urinary kryptopyrroles (UKP), or the ‘Mauve factor’, was first described in in the early 1960s with an observed association with psychiatric illness. Since this time, there has been growing interest in the clinical importance of UKP testing for a range of clinical conditions. However, there are substantive gaps in the available evidence to inform appropriate application and interpretation of UKP tests. With this in mind, this study describes the observed health conditions, treatments and diagnostic application of UKP by clinicians using it within their clinical practice.
Methods
Observational cross-sectional self-report online survey of Australian clinicians, recruited through a company that provides functional testing (including UKP analysis), who identify as having used UKP testing within their clinical practice. The survey collected data on participant demography and characteristics of their clinical practice, their approach to the diagnosis and interventions used to clinically manage elevated UKP (eUKP), and the observed clinical importance of eUKP for a range of health conditions.
Results
The survey was completed by 86 respondents. The majority of participants used nutritional supplements (76.7%), dietary therapy (60.5%) and lifestyle changes (58.1%) to clinically manage eUKP. Nervous system (86.0%) and gastrointestinal (64.0%) conditions were most commonly observed by respondents to be linked to eUKP. Anxiety was observed by 91.9% of respondents to be associated with eUKP and was also the condition most commonly described as markedly improving following treatment of eUKP. A number of factors were reported to be associated with eUKP by the majority of respondents including mood swings (100%), social withdrawal (92.5%), compulsive behaviour (82.4%) and emotional eating (77.8%).
Implications
Given the substantive gaps in evidence associated with UKP testing, this data may provide direction for researchers to design projects that reflect UKP testing as it is used in grass-roots clinical practice.
... However, more importantly for the treatment of ADHD, histamine is found in high concentrations in neurons in the hypothalamus, from where it mediates arousal and attention. Pfeiffer and colleagues 61 found that approximately 50% of their outpatient schizophrenics were "histapenic" (low in blood histamine) and high in blood serum copper, and 20% were histadelic (high in blood histamine) and normal in serum copper. They also found that either group may be low in serum zinc and/or manganese. ...
... They found that these patients responded to large supplementary doses of vitamin B6, zinc and manganese. 61 Such individuals have very low RBC zinc and require heavy supplementation of zinc and vitamin B6. Pyrolurics can exhibit severe behavioral disorders, have a low frustration threshold and lose their temper easily. ...
... The disorder is familial and is responsible for the high incidence of behavioral disorders and schizophrenia in families, with an incidence of 30-40% in schizophrenics and only 5-10% in the normal population. 61 Kryptopyrroles increase in the blood during stress, and zinc and B6 rapidly become unavailable for neurotransmitter synthesis. ...
Many studies have highlighted the fact that our modern diet of processed foods, containing additives, colorings and preservatives, is far removed from those of our evolutionary ancestors and is a major contributing factor to modern diseases. This chapter reviews literature that indicates that most Americans and Australians are not getting the recommended daily intake of key nutrients for optimum general and mental health. The role of omega-3 essential fatty acids, zinc, magnesium, B vitamins and other enzyme cofactors is reviewed in the context of the symptomatology of ADHD. Specific mechanisms are described to illustrate that these nutrients are necessary for serotonin, dopamine and norepinephrine metabolism, and how deficits can promote ADHD. The message to practitioners is that whereas neurotherapy can help the brain to allocate resources appropriately and improve brain function, nutrient supplementation can help provide the optimum biological substrate that facilitates and enhances the changes that neurotherapy can bring about.
... However, more importantly for the treatment of ADHD, histamine is found in high concentrations in neurons in the hypothalamus, from where it mediates arousal and attention. Pfeiffer and colleagues 61 found that approximately 50% of their outpatient schizophrenics were "histapenic" (low in blood histamine) and high in blood serum copper, and 20% were histadelic (high in blood histamine) and normal in serum copper. They also found that either group may be low in serum zinc and/or manganese. ...
... They found that these patients responded to large supplementary doses of vitamin B6, zinc and manganese. 61 Such individuals have very low RBC zinc and require heavy supplementation of zinc and vitamin B6. Pyrolurics can exhibit severe behavioral disorders, have a low frustration threshold and lose their temper easily. ...
... The disorder is familial and is responsible for the high incidence of behavioral disorders and schizophrenia in families, with an incidence of 30-40% in schizophrenics and only 5-10% in the normal population. 61 Kryptopyrroles increase in the blood during stress, and zinc and B6 rapidly become unavailable for neurotransmitter synthesis. ...
This book chapter presents the rationale for Nutrition in ADHD and Autism. However the principles can be applied to any physical and mental health condition. for the Author's views on causes of ADHD and Autism, look up: www.autism-adhd.org.au
... 59 Over decades, clinicians formed the strong opinion that, irrespective of behavioral diagnosis, stress increases associated symptoms and excretion of Mauve. 11,16,30 Pfeiffer came to state unequivocally that Mauve is "a stress-induced factor." 14(p775) Sohler reportedly induced HPL with experimental stress. ...
... Discontinuation may result in severe deterioration within 48 hours. 11 Clinicians report proportionality between Mauve excretion and symptom severity 30 and according to the late Hugh Riordan, MD, former director of the Center for the Improvement of Human Functioning International, Wichita, Kansas (oral communication, 2000), higher Mauve excretion usually requires higher dosages of B 6 and zinc for suppression. HPL in urine decreased progressively with higher B 6 dosing, 16 and progressive B 6 dosing associates with normalization of erythrocyte glutamate oxaloacetate transaminase (EGOT). ...
... Later, some patients were noted to respond optimally to B 6 and as much as 160 mg daily of elemental zinc. 11 In the collective experience of the authors, long-term treatment with B 6 and zinc usually is needed for ongoing HPL suppression and symptom management. Optimal initial dosages may be higher than maintenance dosages. ...
"Mauve Factor" was once mistaken for kryptopyrrole but is the hydroxylactam of hemopyrrole, hydroxyhemopyrrolin-2-one (HPL). Treatment with nutrients--particularly vitamin B6 and zinc--reduces urinary excretion of HPL and improves diverse neurobehavioral symptoms in subjects with elevated urinary HPL. Heightened HPL excretion classically associates with emotional stress, which in turn is known to associate with oxidative stress. For this review, markers for nutritional status and for oxidative stress were examined in relationship to urinary HPL. In cohorts with mixed diagnoses, 24-hour urinary HPL correlated negatively with vitamin B6 activity and zinc concentration in red cells (P < .0001). Above-normal HPL excretion corresponded to subnormal vitamin B6 activity and subnormal zinc with remarkable consistency. HPL correlated inversely with plasma GSH and red-cell catalase, and correlated directly with plasma nitric oxide (P < .0001). Thus, besides implying proportionate needs for vitamin B6 and zinc, HPL is a promising biomarker for oxidative stress. HPL is known to cause non-erythroid heme depression, which lowers zinc, increases nitric oxide, and increases oxidative stress. Administration of prednisone reportedly provoked HPL excretion in animals. Since adrenocorticoid (and catecholamine) stress hormones mediate intestinal permeability, urinary HPL was examined in relationship to urinary indicans, presumptive marker for intestinal permeability. Urinary HPL associated with higher levels ofindicans (P < .0001). Antibiotics reportedly reduce HPL in urine, suggesting an enterobic role in production. Potentially, gut is reservoir for HPL or its precursor, and stress-related changes in intestinal permeability mediate systemic and urinary concentrations.
... Some of these studies date back to the 1970s. In a case study of over 300 polyuric (malvaria) patients seen in their clinic, Pfeiffer, Sohler, Jenney, and Iliev (1974) found that a treatment consisting of B6 and zinc was very efficacious in facilitating a remission of psychosis symptoms. These symptoms generally returned when the patient discontinued these nutrients. ...
... A review of the literature reveals that zinc could be an extremely critical factor in the onset and progression of schizophrenia (Pfeiffer, Sohler, Jenney, & Iliev 1974;Kaslow, 2010). ...
Although the research related to understanding the symptoms and linkages are important in the treatment of schizophrenia, finding the etiological foundations will go much further in the prevention and potential reduction of this disorder. An examination must be made into not only whether schizophrenia has its etiological base in genetics, but whether there are certain nutritional/mineral factors that may be at the root of the onset of schizophrenic symptoms. Isolating the genes that have a direct correlation to schizophrenia has proven to be both difficult and elusive. There have been attempts to link the pathophysiology of this disorder to mineral excess/deficiencies. Many essential trace elements play a role in metabolic pathways which may play a role in schizophrenia. An examination of the literature reveals that zinc could be an extremely critical factor in the onset and progression of schizophrenia.
... Research in the 1970s showed that the mauve factor is the hemopyrrole derivative HPL [36,37]. Furthermore, patients with HPL show deficiencies in in the levels of zinc and vitamin B6, as evinced, inter alia, by Pfei↵er [38]. The connection between HPL and deficiencies in essential metals, as well as the association of HPL with mental illness, are controversially discussed in a review by the Robert-Koch-Institute. ...
Every day huge amounts of medical records are stored by means of hospitals’ and medical offices’ software. These data are generally unconsidered in research. In this work anonymized everyday medical records ascertained in a physician’s office, cov- ering holistic internal medicine in combination with orthomolecular medicine, are analyzed. Due to the lack of cooperation by the provider of the medical practice software a selection of diagnoses and anthropometric parameters was extracted manually. Information about patients’ treatment are not available in this study. Nevertheless, data mining approaches in- cluding machine learning techniques are used to enable research, prevention and monitoring of patients’ course of treatment. The potential of these everyday medical data is demonstrated by investigating co-morbidity and pyroluria which is a metabolic dysfunction indicated by increased levels of hydroxy- hemopyrrolin-2-one (HPL). It points out that the metabolic syndrome forms a cluster of its components and cancer, as well as mental disorders are grouped with thyroid diseases including autoimmune thyroid diseases. In contrast to prevailing assumptions in which it was estimated that approximately 10 % of the population show increased levels of HPL, in this analysis 84.9 % of the tested patients have an increased concentration of HPL. Prevention is illustrated by using decision tree models to predict diseases. Evaluation of the obtained model for Hashimoto’s disease yield an accuracy of 87.5 %. The model generated for hypothyroidism (accuracy of 60.9 %) reveals shortcomings due to missing information about the treatment. Dynamics in the biomolecular status of 20 patients who have visited the medical office at least one time a year between 2010 and 2014 for laboratory tests are visualized by STATIS, a consensus analysis based on an extension to principal component analysis. Thereby, one can obtain patterns which are predestinated for specific diseases as hypertension. This study demonstrates that these often overlooked everyday data are challenging due to its sparsity and heterogeneity but its analysis is a great possibility to do research on disease profiles of real patients.
... Riboflavin supplementation has been demonstrated to restore glutathione activity (61) and N acetyl cysteine, an intermediate substrate in the transulfuration pathway from homocysteine to glutathione (Figure 1), may also offset glutathione synthesis deficiency in settings of oxidative stress (113). Such combination therapy has already been proposed with zinc and B6 supplementation trialed to reduce elevated HPL levels (114). Zinc supplementation reduces excess free copper and moderates copper effects in relationship to neurotoxicity, oxidative stress, thyroid damage and poor FMN synthesis (115,116). ...
The Mental Health Biomarker Project (2010–2016) explored variables for psychosis in schizophrenia and schizoaffective disorder. Blood samples from 67, highly characterized symptomatic cases and 67 gender and age matched control participants were analyzed for methyl tetrahydrofolate reductase (MTHFR) 677C → T gene variants and for vitamin B6, B12 and D, folate, unbound copper, zinc cofactors for enzymes in the methylation cycle, and related catecholamine pathways. Urine samples were analyzed for indole-catecholamines, their metabolites, and oxidative-stress marker, hydroxylpyrolline-2-one (HPL). Rating scales were Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, Global Assessment of Function scale, Clinical Global Impression (CGI) score, and Social and Occupational Functioning Assessment Scale (SOFAS). Analysis used Spearman’s correlates, receiver operating characteristics and structural equation modeling (SEM). The correlative pattern of variables in the overall participant sample strongly implicated monoamine oxidase (MAO) enzyme inactivity so the significant role of MAO’s cofactor flavin adenine nucleotide and its precursor flavin adenine mononucleotide (FMN) within the biochemical pathways was investigated and confirmed as 71% on SEM of the total sample. Splitting the data sets for MTHFR 677C → T polymorphism variants coding for the MTHFR enzyme, discovered that biochemistry variables relating to the wild-type enzyme differed markedly in pattern from those coded by the homozygous variant and that the hereozygous-variant pattern resembled the wild-type-coded pattern. The MTHFR 677C → T-wild and -heterozygous gene variants have a pattern of depleted vitamin cofactors characteristic of flavin insufficiency with under-methylation and severe oxidative stress. The second homozygous MTHFR 677TT pattern related to elevated copper:zinc ratio and a vitamin pattern related to flavin sufficiency and risk of over-methylation. The two gene variants and their different biochemical phenotypes govern findings in relationship to case-identification, illness severity, duration of illness, and functional disability in schizophrenia and schizoaffective psychosis, and establish a basis for trials of gene-guided precision treatment for the management of psychosis.
... 13,14 A polymorphism for CPOX increases isocoproporphyrins, as do toxins such as mercury, 15 diazinon, 16 and hexachlorobenzene. 14 Suggestively, urinary coproporphryin concentrations were greater in high-Mauve schizophrenics than other schizophrenics, 17 and intraperitoneal injection of rats with 0.65 μmol/kg of HPL (Cutler's low dose, as discussed in part 1 of this article) quintupled urinary coproporphyrins. 18 The formation of isocoproporphyrin from altered human heme biosynthesis requires participation of gut fl ora. ...
"Mauve Factor" was once mistaken for kryptopyrrole but is the hydroxylactam of hemopyrrole, hydroxyhemopyrrolin-2-one (HPL). Treatment with nutrients-particularly vitamin B(6) and zinc reduces urinary excretion of HPL and improves diverse neurobehavioral symptoms in subjects with elevated urinary HPL. Heightened HPL excretion classically associates with emotional stress, which in turn is known to associate with oxidative stress. For this review, markers for nutritional status and for oxidative stress were examined in relationship to urinary HPL. In cohorts with mixed diagnoses, 24-hour urinary HPL correlated negatively with vitamin B6 activity and zinc concentration in red cells (P<.0001). Above-normal HPL excretion corresponded to subnormal vitamin B6 activity and subnormal zinc with remarkable consistency. HPL correlated inversely with plasma GSH and red-cell catalase, and correlated directly with plasma nitric oxide (P<.0001). Thus, besides implying proportionate needs for vitamin B(6) and zinc, HPL is a promising biomarker for oxidative stress. HPL is known to cause non-erythroid heme depression, which lowers zinc, increases nitric oxide, and increases oxidative stress. Administration of prednisone reportedly provoked HPL excretion in animals. Since adrenocorticoid (and catecholamine) stress hormones mediate intestinal permeability, urinary HPL was examined in relationship to urinary indicans, presumptive marker for intestinal permeability. Urinary HPL associated with higher levels of indicans (P<.0001.). Antibiotics reportedly reduce HPL in urine, suggesting an enterobic role in production. Potentially, gut is reservoir for HPL or its precursor, and stress-related changes in intestinal permeability mediate systemic and urinary concentrations. (Altern Ther Health Med. 2008;14(3):56-62.)
... Hoffer claimed that HPL tended to decrease when a patient recovered from illness, and increased when illness reappeared; moreover, treatments with vitamin B6 and zinc were reported to decrease HPL levels and were associated with patient recovery [11]. Some psychiatrists, particularly those with interests in orthomolecular medicine, have used HPL as a clinical tool for diagnosing and following the progression or remission of mental illness [11][12][13][14][15][16][17]. Data from these studies suggest that roughly one-third of schizophrenia patients tested had elevated pyrroles, but high urine HPL levels were not limited to schizophrenia, as a variety of conditions and stresses were associated with urine pyrrole excretion. ...
Background : Psychiatrists started using urine pyrroles (hydroxyhemopyrrolin-2-one, HPL) to diagnose psychiatric disorders many years ago. The biological origins of HPL are not known, nor are the causes of elevated urinary pyrrole excretion well understood. Methods : In the present study we analyzed the level of pyrroles in 148 patients with schizophrenia, 135 patients with bipolar disorder, 97 patients with depression, 119 patients with ADHD and compared these data with the results of pyrrole tests for patients with non-psychiatric conditions and healthy volunteers. Results : According to our data, urinary pyrrole concentrations tended to be high in patients with psychiatric disorders, but elevated level of pyrroles was not specific for only these patients. We found evidence of an allergy related component in the fact that elevated pyrrole levels were significantly more prevalent in subjects with elevated histamine values. A role of intestinal bacteria, or imbalances in intestinal bacterial metabolism, was also suggested based on the found relationship between elevated pyrrole levels and elevations in indicans and urobilinogens. In addition, our data demonstrated that subjects with severely elevated pyrrole levels were deficient in nutrients such as zinc, vitamin B3, and vitamin C. Conclusion : Thus, pyrrole excretion seems to be a component of illness in general and not strictly psychiatric disorders.
... Insulin, pyridoxal phosphate, zinc and magnesium are required for the delta-6-desaturase to convert cis-linoleic acid into GLA (). Pyroluric schizophrenic patients, with elevated urinary kryptopyrole (Pfeiffer et al., 1972a) may have a disturbance in delta-6 desaturase and elevated levels of cis-linoleic acid since the important cofactors vitamin B6 and zinc may be differentially lacking in these patients (Pfeiffer et al., 1974).Figure 4 shows blocking factors between stored DGLA and free DGLA and between free DGLA and PGE-1. Methadone, dilantin, lithium, parlodel and methionine — block the formation of PGE-1 and also are used in the treatment of histadelia (high histamine). ...
It has long been accepted that schizophrenia is primarily a physical illness resulting from a chemical imbalance in the brain. This paper will review evidence supporting the hypothesis that histamine and prostaglandins are both linked and primary in the etiology of schizophrenia. Furthermore, their etiological significance supersedes the role of dopamine as a primary causative factor.
... This is a substance first discovered by Irvine et al. (1969) primarily in schizophrenic patients under our direction (Hoffer and Osmond, 1963). Later Pfeiffer (1975) and Pfeiffer et al. (1974) developed a quantitative assay and demonstrated KP bound irreversibly with zinc and pyridoxine causing a double deficiency. KP is an animal hallucinogen (Walker, 1975); it has not been tested in humans. ...
This paper reviews the current status of the adrenochrome theory of schizophrenia. An account is first given of all the experiments in which adrenochrome was reported to induce psychotomimetic effects in normal volunteers. Then the evidence is presented that adrenochrome may actually occur in the brain as a metabolite of adrenaline in the C2 group of adrenergic neurons in the medulla, together with an account of current ideas of the function of these neurons in higher limbic functions. Lastly the recent evidence is reviewed that the gene for the enzyme glutathione S-transferase is defective in schizophrenia. This enzyme detoxifies adrenochrome.
Abstract : Cerebral Palsy (CP) is often accompanied with cognitive, speech and language impairments. The purpose of the research was to examine the risk factors such as length of gestation, complications during pregnancy, birth weight and length linked to the occurrence of CP, as well as speech and language impairments in children with CP. The sample included 67 children with CP. The data used is taken from the documentation of categorization of children handicapped in the psycho-physical development, during the two year period from January, 1st 2008 to December, 31st 2009. There is prevalence in male children compared to the female. Most of the children belong to the category with multiple disabilities, then the categories of physical disability, categories of mental retardation and category of other disorders. The average length of gestation in the sample was 37.36 gestational weeks. The average birth weight was 2833 g. The average birth length was 50.1 cm. Complications during pregnancy were reported in 56.7% and complications during childbirth in 59.7% of the sample. Both complications, during pregnancy and during childbirth, were present in 25 children (37.31 % of the sample). There are 11 children without speech impairments (16.4%) and with speech impairment there are 56 children (83.6%). Value of an average length of gestation; the average birth weight and length of the sample are less than the value of the average population. Complications of pregnancy and childbirth are significantly represented in the sample. For some children both complications were present. Most of the children in the sample have multiple disabilities. At 83.6% of children, speech and language impairments were found.
• Ensure that your lab tests for mauve factor • Mauve was identified in the urine of some mental-health patients • Carl Pfeiffer first developed the calorimetric test for mauve • Mauve is not kryptopyrrole but hydroxyhaemopyrrolin-2-one (HPL) • Mauve factor causes deficits in zinc and vitamins B6 and B3 • Treatment may require aggressive supplementation with zinc citrate and both B6 and pyridoxal-5- phosphate • AA and/or EPA and DHA may be low in persons with mauve factor • Testing red blood-cell EFA helps titrate AA, EPA and EPO • Red blood-cell zinc (not serum zinc) is essential for monitoring zinc levels.
Background: Psychiatrists started using urine pyrroles (hydroxyhemopyrrolin-2-one, HPL) to diagnose psychiatric disorders many years ago. The biological origins of HPL are not known, nor are the causes of elevated urinary pyrrole excretion well understood. Methods: In the present study we analyzed the level of pyrroles in 148 patients with schizophrenia, 135 patients with bipolar disorder, 97 patients with depression, 119 patients with attention deficit hyperactivity disorder, and compared these data with the results of pyrrole tests for patients with non-psychiatric conditions and healthy volunteers. Results: According to our data, urinary pyrrole concentrations tended to be high in patients with psychiatric disorders, but elevated level of pyrroles was not specific for only these patients. We found evidence of an allergy related component in the fact that elevated pyrrole levels were significantly more prevalent in subjects with elevated histamine values. A role of intestinal bacteria, or imbalances in intestinal bacterial metabolism, was also suggested based on the found relationship between elevated pyrrole levels and elevations in indicans and urobilinogens. In addition, our data demonstrated that subjects with severely elevated pyrrole levels were deficient in nutrients such as zinc, Vitamin B3, and Vitamin C. Conclusion: Thus, pyrrole excretion seems to be a component of illness in general and not strictly psychiatric disorders.
The possible biochemical imbalances involved in the schizophrenias can now confidently be divided into five possible factors. These are low blood histamine (histapenia); high blood histamine (histadelia); pyroluria or malvaria due to the urinary mauve factor kryptopyrrole; cerebral allergy, and hypoglycemia. The combinations of these five basic biochemical imbalances number 23, which sounds formidable; but since all five basic factors can be measured, the treatment of all combinations is now possible.
This case report describes a man with aggressive and anti-social behaviors, a 47, XYY karyotype, abnormally elevated urinary kryptopyrroles and multiple brain injuries who is now serving a 250 year sentence for the serial murders of 11 women. These multiple abnormal findings have relevance as identifiable precursors for potential violence in such individuals with a history of behavioral disturbance and are discussed on a background of his case history and review of the literature.
The essential trace elements zinc and manganese have been noted as factors in brain disease since the Twenties. The combined use of zinc and manganese in schizophrenia is based on the following: increased urinary excretion of copper when both zinc and manganese are given orally; zinc alone causes a decrease in blood manganese; and the double deficiency of zinc and manganese frequently is found in patients with excess copper. The mauve factor (Kryptopyrrole) is known to increase the excretion of zinc and vitamin B6 (pyridoxine). Manganese is important in the building and breakdown cycles of protein and nucleic acid. For RNA chain initiation, manganese was found to be a better effector than magnesium. Manganese stimulates adenylate cyclase activity in brain tissue. Because cyclic-AMP plays a regulatory role in the action of several brain neurotransmitters, manganese is important in brain function. Owing to the fact that zinc is well absorbed from the gut but manganese is poorly absorbed all diagnostic categories may be harmed by large prolonged oral doses of zinc without manganese. In oral doses manganese occasionally elevates blood pressure in patients over 40 years of age. Zinc alone can lower blood pressure in some hypertensive patients. Prolonged use of phenothiazines causes tardive dyskinesia. Phenothiazines might chelate manganese making it unavailable for some presumed function as an enzyme activator.
If a standardized program of Megavitamin Therapy (MVT) and/or Lithium Orotate Therapy (LOT) are added to programs of psychotherapy, there should be seen measurable, observable and statistical differences in before and after populations as measured by the Minnesota Multiphasic Personality Inventory (MMPI). Thirty-two subjects, in a matched group design, each were assigned to seven groups (N=224): No Treatment Group, Psychotherapy Only Group, Psychotherapy and Megavitamin Therapy Group, and the Lithium Orotate, Psychotherapy, and Megavitamin Therapy Group. The last three groups had before and after subjects. The No Treatment Group was tested and then abandoned. Each of the specific groups were administered the full MMPI both upon admission to the treatment program and at the point of discharge. These groups were balanced for sex, religion, occupation, educational level, and race. The results were statistically significant. They demonstrated that time in therapy was reduced by seven months, Megavitamin Therapy was 66% more effective than Psychotherapy Only; it was therefore cost-effective. Whereas, MVT and LOT were only 8% more effective. Introduction/Motivation for the Study During the past decade the writer has observed the most common diagnosis for his patients to be: 296.23 Major Depression, Single Episode Without Psychotic Features. The average length in therapy was twelve to eighteen months. The author, without formal train-
A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.
The hypothesis presented here suggests that schizophrenia is caused by the action of gestational zinc deficiency on genetically susceptible foetuses. The psychosis seen is suggested to be due to a combination of dietary or otherwise induced zinc deficiency and lack of zinc releasing capacity in the hippocampus. A non genetic but transmissable immune defect is suggested to be relevant to psychosis and to the nonmendelian pattern of inheritance of the disorder.
Dopamine has been accepted as a possible etiological factor in schizophrenia and most studies have demonstrated that the ingestion of methionine by schizophrenics exacerbated their psychosis. Unfortunately, the methylation theory has failed to support the dopamine theory in schizophrenia. This paper will attempt to demonstrate why abnormal histamine metabolism in schizophrenia can explain the effect of methionine in worsening schizophrenia in certain patients.
Few complementary and alternative medicine (CAM) institutions require their students to undergo substantive training in research literacy and conduct, and well-developed programs to train CAM institution faculty in research are virtually non-existent. As part of a National Center for Complementary and Alternative Medicine (NCCAM) initiative to increase research capacity at CAM institutions, the New England School of Acupuncture (NESA), in collaboration with the Harvard Medical School (HMS) Osher Institute, was awarded a Developmental Center for Research on Complementary and Alternative Medicine (DCRC) grant. This article discusses a number of initiatives that we designed and implemented to train NESA students, faculty members, and alumni in the foundations of clinical research and to stimulate interest in both participating in research and receiving additional research training. Specific initiatives included a 30-hour faculty "Foundations of Research" course; a year-long course entitled, "How to Write a Publishable Case Report"; institution of a monthly research seminar series; revision of an already required student research course; and the addition of 2 new student-mentored independent research electives. We discuss successes and challenges encountered in developing and administering these initiatives and the overall impact they have had on research culture and productivity at NESA.
This chapter discusses zinc deficiency and copper excess in the schizophrenias. Zinc and copper are well-known biological antagonists. Schizophrenics may have low levels of zinc, manganese, chromium, and molybdenum but may also contain high levels of copper, iron, cadmium, and mercury. Plasma zinc levels are significantly reduced in acute liver diseases, active tuberculosis, indolent ulcer, myocardial infarction, Down's syndrome, cystic fibrosis, growth retardation, pregnancy, and oral contraceptive therapies. Hypoglycemias occur frequently in psychic disorders and are misdiagnosed as schizophrenias. Human brain appears to contain more than one type of copper protein, and the one so far isolated has been designated as cerebrocuprein. Its physical properties are almost identical to the copper protein isolated from human liver and from human erythrocytes. Its physiological significance has not been assessed. Copper is an essential trace element and is necessary for supporting life, but an excess in the body can be toxic because the copper ions can inactivate enzymes by reacting with their sulfhydril groups. Porphorins act as chelating agents to increase urinary excretion of both copper and zinc.
USING the drug-induced model psychosis as a guide to urinary constituents relevant to psychotic states, LSD was administered to volunteers and their urines were monitored by paper chromatography. In this way a new, Ehrlich-positive spot isographic with bufotenin was found and subsequently observed in many psychiatric patients not given LSD. In 1961, we named this substance "mauve factor" (because of its Ehrlich reaction), suggested it was pyrrolic, and pointed out its statistical association with psychosis (not specifically schizophrenia)1. Hoffer went further, perhaps prematurely, and suggested that persons excreting mauve factor could be described as suffering from a disease called "malvaria"2. The association between mauve factor and psychosis has been confirmed3-5 and similar trends were observed by others2,6,7,9, the factor usually being present in 30-60 per cent range of psychotic patients.
The authors confirm the reports of an Ehrlich-positive mauve-colored spot on chromatograms of urine extracts in certain schizophrenic patients, and a simplified procedure for performing the test is outlined. Although the data are consistent with earlier observations that certain abnormal materials occur with higher incidence in the urine of schizophrenic patients than in nonschizophrenics, experiments using thin layer chromatography of these materials suggest that the abnormal material may be phenothiazine metabolites.
Malvaria: A New Psychiatric Disease
- J Psychiat
- A Hoffer
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A
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Serum Polyamine Levels in Schizophrenia and Other Objective Criteria of Clinical Status, Schizophrenia Current Concepts and Research
- C C Pfeiffer
- V Iliev
- L Goldstein
PFEIFFER, C.C, ILIEV, V., GOLDSTEIN, L, and JENNEY, E.H.:
Serum Polyamine Levels in Schizophrenia and Other Objective
Criteria of Clinical Status, Schizophrenia Current Concepts and
Research, PJD Publications, Hicksville, N.Y., 1969.
Mauve Spot and Schizophre nia
- G L Ellman
- R T Jones
- R C Hoffer
ELLMAN,
G.L.,
JONES,
R.T., and
RYCHERT
,
R.C.:
Mauve
Spot and
Schizophre
nia. Amer.
J. Psychiat.
125:161,
1968.
HOFFER,
A.,
and
OSMOND,
H.:
Malvaria:
A
New
Psychiatric
Disease.
Acta
Psvchiatric
a Scandinavica 39:335, 1963.
C: Biochemical Relationship Between Kryptopyrrole (Mauve Factor) and Trans 3 Methyl 2Hexenoic-Acid (Schizophrenia Odor)
K R I S C H E R, K., and PFEIFFER, C.C: Biochemical Relationship
Between Kryptopyrrole (Mauve Factor) and Trans 3 Methyl 2Hexenoic-Acid (Schizophrenia Odor). Res. Comm. Chem. Path,
and Pharm. 5:9, 1973.