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Assessment of vitamin [B.sub.1] status.

To the Editor:

The excellent report by Talwar et al. (1) promotes the measurement of thiamin diphosphate (TDP) for the assessment of vitamin [B.sub.1] status. My experience with >30 000 people supports this, but only for the investigation of untreated patients.

The TDP assay is more precise than the transketolase activation (ETK) test, and the method described is an important advance for which I thank the authors. In comparing the I two methods, Talwar et al. (1) found TDP slightly advantageous in the identification of [B.sub.1] deficiency. They and most workers using the ETK test agree that the cutoff point is 25%. I have found it useful to report results in the range 15-25% as borderline. When this is done, there is little to choose between TDP and ETK in terms of clinical usefulness.

Much as I would like to use the more precise TDP assay, there is a

problem that surfaces when one wishes to use the laboratory to follow repletion with thiamin. It is very rare for the TDP concentration to remain low after a few days of supplemental [B.sub.1], and in many cases, TDP normalizes after a single 100-mg dose. This is not the case for the ETK test. In some cases, several weeks of daily supplementation are needed to normalize the results.

I am in the fortunate position of receiving considerable feedback from the clinicians using our laboratory service and have carefully studied their findings in relation to the laboratory results. In my experience, it is the ETK test that parallels the clinical improvement in supplemented patients.

I support the use of the more precise TDP (HPLC method) in untreated people, but I caution against its use in following supplementation. For this, the ETK test, even with its many limitations, remains the method of choice. A more precise method for measuring this enzyme would be enormously helpful. I hope this letter will open some further discussion on the use of functional tests in nutrient-related clinical chemistry.

References

(1.) Talwar D, Davidson H, Cooney J, St. JO'Reilly D. Vitamin B1 status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation test. Clin Chem 2000;46:704-10

John McLaren Howard

Biolab Medical Unit

9 Weymouth St.

London W1 N 3FF, United Kingdom

Drs. Talwar and St. JO'Reilly respond:

To the Editor:

Dr. McLaren Howard makes an interesting observation relating to the biochemical assessment of thiamin status in people supplemented with the vitamin. In his experience, the indirect measurement of thiamin status using the transketolase (ETK) activation assay is clinically more useful than direct measurement of thiamin diphosphate (TDP) concentrations in red cells in people repleted with thiamin. Unfortunately, we are unable to comment on his observation because no relevant data are presented.

Discrepancies between the ETK activation test and clinical signs of thiamin deficiency have been reported previously, with several studies reporting no relationship between ETK activation results and thiamin intake (1-5). These discrepant findings have raised questions about the usefulness of the ETK activation test as a sole indicator of thiamin status.

Because a valid ETK activation response depends on a kinetically normal enzyme (1, 6), certain disease states may affect enzyme cofactor binding and hence the TDP activation effect (6). Because of the potential difficulty in interpretation of ETK activation effect in some disease states and the limitations of enzyme activation tests in general, several authors have suggested the use of more direct measures of thiamin status, such as TDP in whole blood or plasma (4, 6, 7).

We would agree with Dr. McLaren Howard that further discussion is required on the merits or otherwise of direct and indirect measures of thiamin status in patients repleted with thiamin. Meanwhile, our experience with the HPLC assay suggests that measurement of TDP in red cells is the single most useful biochemical measurement for assessing thiamin status in patients who are at risk of thiamin deficiency.

References

(1.) Kerr RA, Clague AE, Morris DJ, Price J. The rapid decline in erythrocyte transketolase on cessation of high dose thiamin administration in Korsakoff patients. Alcohol 1986;21:257-62.

(2.) Iber FL, Blass JP, Brin M, Leevy CM. Thiamin in the elderly-relation to alcoholism and to neurological degenerative disease. Am J Clin Nutr 1982;36:1067-82.

(3.) Nordentoft M, Timm S, Hasselbalch E, Roesen A, Gammeltoft S, Hemmingsen R. Thiamin pyrophosphate effect and erythrocyte transketolase activity during severe alcohol withdrawal syndrome. Acta Psychiatr Scand 1993;88:80-4.

(4.) Gans DA, Harper AE. Thiamin status of incarcerated and nonincarcerated adolescent males: dietary intake and thiamin pyrophosphate response. Am J Clin Nutr 1991;53:1471-5.

(5.) Macias-Matos C, Rodriguez-Ojea A, Chi N, Jimenez S, Zulueta D, Bates CJ. Biochemical evidence of thiamin depletion during the Cuban neuropathy epidemic 1992-1993. Am J Clin Nutr 1996;64:347-53.

(6.) McLaren DS, Docherty MA, Boyd DA. Plasma thiamin pyrophosphate and erythrocyte transketolase in chronic alcoholism. Am J Clin Nutr 1981;34:1031-3.

(7.) Dancy M, Evans G, Gaitonde MK, Maxwell JD. Blood thiamin and thiamin phosphate ester concentrations in alcoholic and non alcoholic liver diseases. Br Med J 1984;289:79-82.

Dinesh Talwar *

Denis St. JO'Reilly

Department of Clinical Biochemistry

Macewen Building

Royal Infirmary

Glasgow G4 OSF, United Kingdom

* Author for correspondence.
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Title Annotation:Letters
Author:Howard, John McLaren
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Nov 1, 2000
Words:881
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