Public Health

(1992), 106, 393-395

© The Society of Public Health, 1992

Detection of Subclinical Ascorbate Deficiency in Early Parkinson's Disease S. C. Senarath Yapa, MB BS MRCP (UK) Principal Cfinical Medical Officer, Bury Health Authority, 21 Silver Street, Bury, Lancs, BL9 0EN

From mid-October 1989 to mid-July 1990 all newly admitted residents to Bury Local Authority Residential Homes were comprehensively medically screened. In a series of 100 residents eight had early Parkinson's disease (six of them hitherto undiagnosed). Seven showed evidence of Vitamin C deficiency. Of the seven showing evidence of deficiency, four suffered from early Parkinson's disease. Of the 93 without evidence of Vitamin C deficiency only four had Parkinson's disease. This indicates a significantly higher prevalence of Parkinson's disease in the group with Vitamin C deficiency (P < 0.001 using Fisher's exact).

Introduction This was an observational study in which from mid-October 1989 to mid-July 1990 all elderly residents newly admitted to Bury Local Authority H o m e s (age range 61-98 years, mean age 83.45, SD + 7.56) were medically screened by the author at the respective homes consecutively on referral by the Nurse Adviser to Social Services.

Method Each patient was examined for evidence of early Parkinson's disease. A n y resident with two or more of the following four features was diagnosed as having Parkinson's disease: 1. 2. 3. 4.

characteristic tremor; bradykinesia; cog-wheel type rigidity; festinant gait with or without 'freezing' at doorways.

The presence of corkscrew hairs I (peculiar curled maldeveloped hairs some of which characteristically do not emerge above the epidermis) were diligently looked for as evidence of 'subclinical' Vitamin C deficiency. When present in males they occurred predominantly over the thighs, shins, anterior abdominal wall, front and back of the chest. In females they were seen over the pubic area only. Two of the seven residents with 'corkscrew' hairs had the Vitamin C saturation test. Clinical suspicion of ascorbate deficiency was confirmed by this test in both cases. As the test was cumbersome it was not performed on the others.

Findings The most interesting finding was the significantly higher prevalence of Parkinson's disease in the group with Vitamin C deficiency.

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Discussion The finding of a higher prevalence of Parkinson's disease in the elderly with Vitamin C deficiency is intriguing. What is pertinent to know is whether the occurrence of ascorbate deficiency in Parkinson's disease is only a secondary phenomenon arising from sub-nutrition associated with attendant disabilities and social circumstances, or whether there is a causal link. Humans (and other primates like monkeys and guinea pigs) lack the microsomal enzyme L-gulanolactone oxidase essential for the denovosynthesis of ascorbate, whereas lower vertebrates possess this enzyme. MPTP (methyl phenyl tetrahydro pyridine) induces Parkinson's disease in humans, monkeys and guinea pigs but not in the lower vertebrates with a gulanolactone oxidase system. Ascorbate is known to have strong antioxidant properties and its protective properties on the dopamine neurone, and the prophylactic action on the progression of Parkinson's disease, has been the subject of intense enquiry by many workers of late. Fahn, 2 in an open-labelled pilot study, found that the progression of Parkinson's disease may be slowed by the administration of high dosages of tocopherol and ascorbate. Huyghe and Klinman, 3 investigating the role of intravesicular and extravesicular ascorbate in the turnover of the enzyme dopamine beta-monoxygenase (D beta M), using adrenal medulla chromaffin granules, have demonstrated very clearly that external aseorbate acts as a reductant for the membranous form of D beta M in chromaffin granules. Kalir and Mytilineou, 4 using mesencephalic rat brain cultures, have shown that the presence of ascorbate exerted a broad effect on dopamine neurone morphology and biochemical functioning, including increased glial proliferation, increased neurite growth and number on tyrosine hydroxylase staining. Vescour et al., 5 by monitoring dopamine metabolism in rat phaeochromocytomaderived PC 12 cell cultures, showed that manganese-induced disappearance of extracellular dopamine can be fully prevented by ascorbic acid and not by glutathione. Stewart and Klinman 6 found evidence for ascorbate regulation of D beta M enzyme activity over a range of ascorbate concentrations with apparent negative cooperativity. All the above studies indicate that ascorbate is protective and neurotrophic for the dopamine neurone, and has regulatory activity (a negative cooperativity) on the dopamine betamonooxygenase (D beta M) enzyme system; given in high dosage (with tocopherol) it may delay the progression o f symptoms of Parkinson's disease so delaying the need for medication. Since corkscrew hairs may be detected easily (e.g. by a bath-nurse trained to detect them), screening for corkscrew hairs followed by ascorbate therapy where deficiency is confirmed may have public health and health promotion implications for the elderly in terms of improved quality of life and prevention of falls, etc.

Acknowledgements Thanks to Eileen Prestwich, RGN, Nurse Adviser to Social Services, Bury, for invaluable assistance; Dr Olu Olojugba, Director of Public Health, for encouragement; and Mr Gordon Crossley, Principal Biochemist, for help with biochemical tests.

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References 1. Meiklejohn, A. P. (1956). Clinical features of scurvy. In: Davidson, L.S.P. (ed.). The Principles and Practice of Medicine, 3rd Edition, 417. Edinburgh: E. and S. Livingstone. 2. Fahn, S. (1991). An open trial of high-dosage antioxidants in early Parkinson's Disease. American Journal of Clinical Nutrition, 53(1 suppl.), 380S-382S. 3. Huyghe, B. G. & Klinman, J. P. (1991). Activity of membranous dopamine beta monoxygenase within chromaffin granule ghosts. Journal of Biological Chemistry, 266(18), 11544-11550. 4. Kalir, H. H. & Mytilineou, C. (1991). Ascorbic acid in mesencephalic cultures: effects on dopaminergic neuron development. Journal of Neurochemistry, 57(2), 458-464. g. Vescoir, A. et al. (1991). Dopamine metabolism alterations in a manganese-treated pheochromocytoma cell line (PC12). Toxicology, 67(2), 129-142. 6. Stewart, L. C. & Klinman, J. P. (1991). Cooperativity in the dopamine beta-monoxygenase reaction. Evidence for ascorbate regulation of enzyme activity. Journal of Biological Chemistry, 266(18), 11537-11543.

Detection of subclinical ascorbate deficiency in early Parkinson's disease.

From mid-October 1989 to mid-July 1990 all newly admitted residents to Bury Local Authority Residential Homes were comprehensively medically screened...
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