Discerning the Mauve factor, Part 2.

"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.

Discerning the Mauve Factor, Part 1.

"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 glutathione 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 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 a reservoir for HPL or its precursor, and stress-related changes in intestinal permeability mediate systemic and urinary concentrations.

The two faces of L-DOPA: benefits and adverse side effects in the treatment of Encephalitis lethargica, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis.

Parkinson's disease, encephalitis lethargica, multiple sclerosis and amyotrophic lateral sclerosis patients all display two distinct types of symptoms. Some of these are due directly to a deficiency of dopamine and are quickly reduced by laevodihydroxyphenylalanine (L-DOPA). The second set, however, are the result of neurological damage caused by metabolites of dopamine, which include dopachrome and other chrome indoles that are both hallucinogenic and neurotoxic. If this hypothesis is correct, three corollaries follow. Patients of all four disorders should display excessive oxidative stress, natural methyl acceptors should delay development and elevated antioxidant supplementation, given with L-DOPA, ought to prolong the "honeymoon" period in which the benefits of the drug out weigh its subsequent disadvantages. A literature review suggests that all three corollaries are probably correct.

Schizophrenia and cancer: the adrenochrome balanced morphism.

Cancer might be expected to be more common amongst schizophrenics than the general population. They frequently live in selenium deficient regions, have seriously compromised antioxidant defense systems and chain-smoke. The available literature on the cancer-schizoprenia relationship in patients from England, Wales, Ireland, Denmark, USA and Japan, however, strongly suggests that the reverse is true. One of the authors (Hoffer) has treated 4000 schizophrenics since 1952. Only four of these patients has developed cancer. Since low cancer incidence has been recorded amongst patients treated by both conventional physicians using pharmaceuticals and by orthomolecular doctors who emphasize vitamins and minerals, it follows that this depressed cancer incidence must be related to the biochemistry of the disorder itself. Taken as a whole, therefore, the evidence seems to suggest that schizophrenics, their siblings and parents are less susceptible to cancer than the general population. These relationships seem compatible with one or more genetic risk factors for schizophrenia that offer(s) a selective advantage against cancer. There is experimental evidence that appears to support this possibility. Matrix Pharmaceuticals Inc. has received a US patent covering the composition of IntraDose Injectable Gel. This gel contains cisplatin and epinephrine (adrenaline) and is designed to be injected directly into tumour masses. Cisplatin is a very powerful oxidant which will almost certainly rapidly convert the adrenaline to adrenochrome. While the manufacturers of IntraDose consider cisplatin to be the active cytotoxic agent in IntraDose, it seems more likely that adrenochrome and its derivatives may, in fact, be more effective. IntraDose gel has undergone or is undergoing a series of Phase III open-label clinical studies, being injected into patients' tumours that have been identified as the most troublesome by their physicians. The results have been impressive for breast cancer, malignant melanoma, esophageal cancer and cancer of the head, neck and liver. The evidence suggests that there are balanced morphisms in schizophrenia that result in above normal exposure to catecholamine derivatives. Since such catecholamines are both hallucinogenic and anticarcinogenic abnormally high exposure to them simultaneously increases susceptibility to schizophrenia and reduces the probability of developing cancer. These observations have significant implications for the treatment of both illnesses.