Depression, High-Mauve Factor, & Recent Research

Depression is characterized by a persistent depressed mood and or interest in things that previously gave pleasure, which is a change for that individual.¹ It is estimated that 6.6% of the population in the USA will experience depression.

The mauve factor is hydroxylactam of hemopyrrole, hydroxyhemopyrrolin-3-one (HPL).  Elevated urinary HPL results in neurobehavioral symptoms, which can be improved with nutrients vitamin B6 and zinc.  Increased excretion of HPL is associated with oxidative stress and emotional stress.

High-mauve factor is found in patients with Down syndrome, schizophrenia, autism, ADHD, and alcoholism.² Pfeiffer et al. reports symptoms of high-mauve include upper abdominal pain, hyperactivity, explosive anger, low stress tolerance, and musculoskeletal pain.  These symptoms are expansive and can be difficult to distinguish from many mental health conditions such as major depression and schizophrenia.

The development of depression is complex and two major models in the literature describe the pathogenesis. The monoamine-deficiency hypothesis states that symptoms related to decreased norepinephrine and serotonin in multiple regions of the brain may be responsible for depression.  Abnormalities in the cortisol response, and chronically elevated cortisol may be contributory. Additionally, abnormal circadian rhythms and impaired synthesis or metabolism of neurotransmitters can result in inflammation causing depression. Twin studies suggest a 37% concordance suggesting genetics contribute to the development of depression.

HPL is correlated inversely with plasma glutathione and red-cell catalase, and directly with plasma nitric oxide. High-mauve denotes individuals that excrete excess HPL, and have resulting erythroid heme depression, low zinc, and increased nitric oxide.  Heme depression and increased nitric oxide results in considerable oxidative stress and inflammation throughout the body and brain.  There are many heme-dependent enzymes, which play vital roles in anti-oxidant defense, including catalase, peroxidase, and CYP450 synthesis. 

Heme synthesis begins with condensation of glycine and succinyl-CoA to form d-aminolevulinic acid (ALA). Vitamin B6, or pyridoxal phosphate (PLP) serves as a coenzyme for d-aminolevulinate synthesis (which is the rate-limiting step in heme synthesis). Aminolevulinic acid (ALA) condensation forms porphobilinogen by zinc-containing ALA dehydratase. The porphyrias are classified as erythropoietic or hepatic, depending on where the enzyme deficiency occurs in the erythropoietic cells of the bone marrow, or the liver. 

Depression and other mental health conditions have been associated with mitochondria dysfunction. Bioenergetics and neurodevelopment are highly influenced by mitochondrial function, and poor function is often due to altered redox balance and chronic low-grade inflammation. N-acetylcysteine has protective effects in multiple models of mitochondrial dysfunctions.³

Research completed by Torres et al. demonstrated protective effects in neurotoxicity associated with pyrroles in urine.  The sulfhydryl groups provided by NAC appear to inhibit the pyrrole-pyrrole crosslinking and prevent 2,5-hexanedion toxicity in a rat model.⁴

Anti-depressants, escitalopram, and placebo compared to S-adenosyle methionine (SAMe) showed inferior responses in major depression. Results of the study suggest that SAMe provide evidence for the use of SAMe in major depression.⁵

1.      Domino, Frank J. The 5-minute Clinical Consult Standard. Philadelphia, PA: Wolters Kluwer Health; 2015. 380-381 p.

2.      Pfeiffer, C. C., Sohler, A., Jenney, E. H., & Iliev, V."Treatment of pyroluric schizophrenia (malvaria) with large doses of pyridoxine and a dietary supplement of zinc." J Orthomol Psychiat 3 (1974): 292-300.

3.      Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M. Mitochondrial dysfunction in schizophrenia: Pathways, mechanisms and implications. Neurosci Biobehav Rev. 2015;48:10-21. doi:10.1016/j.neubiorev.2014.11.005.

4.      Torres ME, dos Santos a. PM, Gonçalves LL, Andrade V, Batoréu MC, Mateus ML. Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model: Changes in urinary pyrroles levels and motor activity performance. Environ Toxicol Pharmacol. 2014;38(3):807-813. doi:10.1016/j.etap.2014.09.008.

5.      Sarris J, I. Papakostas G, Vitolo O, Fava M, Mischoulon D. S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: Efficacy and effects of histamine and carnitine as moderators of response. J Affect Disord. 2014;164:76-81. doi:10.1016/j.jad.2014.03.041.