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Severe experimental folate deficiency in a human subject - a longitudinal investigation of red-cell folate immunoassay errors as megaloblastic anaemia develops.

ABSTRACT: BACKGROUND:The few published studies comparing results between commercial red-cell folate immunoassays have found significant differences. None have provided longitudinal data during the development of megaloblastic anaemia from severe folate deficiency. The objective was to produce longitudinal data, comparing results between three commercial immunoassays for red-cell folate, generated by means of severe experimental folate deficiency. METHODS:This 58 year old male, initially replete in folate, used a folate-deficient diet to severely deplete himself of folate until overt megaloblastic anaemia developed. The Siemens Advia Centaur, Roche Elecsys 2010 and Beckman UniCel DxI 800 Access immunoassay systems were used, by different clinical pathology laboratories, to perform weekly assays for red-cell folate throughout the depletion stage. The results were analysed graphically four ways: comparison with lines of equality; number of standard deviations difference against the means; number of standard deviations difference over time; variation over time. RESULTS:There were very significant differences, varying with time and folate concentration, between the results reported by the three laboratories. The differences were greatest, up to 17 standard deviations, between the Siemens Advia Centaur and each of the other two systems. Of the 85 results comparing the Siemens Advia Centaur and the Roche Elecsys 2010, two were within the 99.9% confidence interval. Of the 91 results comparing the Siemens Advia Centaur and the Beckman UniCel DxI 800 Access, 22 were within the 99.9% confidence interval. Of the 83 results comparing the Beckman UniCel DxI 800 Access and the Roche Elecsys 2010, 37 were within the 99.9% confidence interval. CONCLUSIONS:Comparative longitudinal data from clinical pathology laboratories, produced during experimental folate deficiency, have exposed very significant differences in results between commercial red-cell folate immunoassays. One immunoassay, the Roche Elecsys 2010, failed to detect overt megaloblastic anaemia of severe folate deficiency.

SUBMITTER: Golding PH

PROVIDER: S-EPMC4190184 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Severe experimental folate deficiency in a human subject - a longitudinal investigation of red-cell folate immunoassay errors as megaloblastic anaemia develops.

Golding Paul Henry PH

SpringerPlus 20140923

<h4>Background</h4>The few published studies comparing results between commercial red-cell folate immunoassays have found significant differences. None have provided longitudinal data during the development of megaloblastic anaemia from severe folate deficiency. The objective was to produce longitudinal data, comparing results between three commercial immunoassays for red-cell folate, generated by means of severe experimental folate deficiency.<h4>Methods</h4>This 58 year old male, initially rep ...[more]

PMID: 25332849

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Project description:BackgroundThe currently accepted theory, that the human liver store of folate is limited to about four months, is based on the findings of Victor Herbert and others of the era before folate fortification of food. A recent model, developed by Lin et al., predicts far greater liver folate storage capacity than reported by Herbert. The conflict between Herbert's and Lin's models needs to be resolved experimentally, however current research is restricted because ethical considerations prevent such risky experimentation on patients or healthy human volunteers. The objective was to provide a detailed record of the biochemical and haematological responses to the development of severe experimental folate deficiency in an initially replete human subject.MethodsThis 58 year old male severely depleted himself of folate, using a folate-deficient diet, until overt megaloblastic anaemia developed. The biochemical and haematological responses were monitored by routine blood tests. Daily intake of dietary supplements prevented deficiencies of other relevant nutrients.ResultsThe rate of change of all analytes was significantly slower, and the delay before any change for several analytes was significantly longer, than reported for previous experiments. The time before reporting of abnormal biochemical and haematological results was therefore very significantly longer than reported by Herbert, but was consistent with the recent model of Lin et al. Serum folate and red-cell folate became abnormally low after 219 and 413 days respectively. Macrocytic anaemia was produced after 469 days, and megaloblastic anaemia was confirmed by bone marrow biopsy on day 575. Folate starvation ceased on day 586, and recovery was complete on day 772.ConclusionsThe currently accepted four month time scale for development of megaloblastic anaemia from folate deficiency, based on the early work of Herbert and others, is not consistent with the results from this study. The > 300 day liver folate storage time, predicted by the model of Lin et al., is supported by this experiment. Self-experimentation has produced a detailed record of the biochemical and haematological responses to severe experimental folate deficiency, whereas using patients or healthy volunteers as subjects would be unethical.

Dataset Information

Severe experimental folate deficiency in a human subject - a longitudinal investigation of red-cell folate immunoassay errors as megaloblastic anaemia develops.

Publications

Severe experimental folate deficiency in a human subject - a longitudinal investigation of red-cell folate immunoassay errors as megaloblastic anaemia develops.

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