1017

THE AMERICAN JOURNAL OF CLINICAL NUTRITION

Vol. 23, No. 8, August, 1970, pp. 1017-1026

Printed in U.S.A.

Original Communications

Clinical and Biochemical Studies

of Adult Beriberi13

VICHAI TANPHAICHITR,4 M.D., SERENE L. VIMOKESANT,5 D.SC.

SAKHORN DHANAMITrA,#{176} M.D., D.SC.

AND AREE VALYASEVI,7 M.D. D.SC.

B RIN AND HIS CO-WORKERS have shown

that the activity of erythrocyte trans-

ketolase (ETK) can be used to detect the

biochemical defect in thiamin deficiency

before clinical manifestations appear (1-

3). Several studies in Thailand (4-6) using

dietary survey techniques, urinary thiamin

excretion, or the thiamin pyrophosphate

stimulatory effect (TPP effect) on ETK

or all of these as critelia (7) indicate that

beriberi is still a public health problem in

Thailand. It was the purpose of this study

to determine if a correlation exists between

the biochemical tests, including urinary

thiamin excretion and the TPP effect,

and! clinical manifestations of beriberi in

adlults.

1 From the Faculty of Medicine, Ramathibodi

Hospital and the Faculty of Medicine and Siriraj

Hospital, Mahidol University, Bangkok, Thailand.

2 Supported in part by National Institute of

Health Grant A-592l, the SEATO Clinical Re

search Center, and the Thai National Research

Council.

‘Address requests for reprints to: Aree Valyasevi,

M.D., I)epartment of Pediatrics, Ramathibodi Hos-

pital, Rama VI Road, Bangkok 4, Thailand.

Instructor, Department of Medicine, Faculty

of Medicine, Ramathibodi Hospital. ‘Lecturer,

Department of Biochemistry, Faculty of Sciences.

#{176}Lecturer, Department of Pediatrics, Faculty of

Medicine, Ramathibodi Hospital. Professor and

Chairman, Department of Pediatrics, Faculty of

Medicine, Ramathibodi Hospital.

MATERIALS AND METHODS

Twenty-one patients (22 observations, P1

was admitted twice) were clinically diagnosed

as beriberi and were studied at Siriraj Hospital,

Bangkok, Thailand. The diagnosis was based

on 1) a dietary history that suggested the thia-

mm intake was low, 2) edema with or without

symptoms and signs of cardiac failure in wet

beriberi, 3) evidence of peripheral neuropathy

without other known causes, and 4) good clini-

cal response to thiamin administration. Serial

chest roentgenograms and electrocardiograms

were obtained before and after thiamin admin-

istration. Blood samples were drawn for the de-

termination of ETK activity and TPP effect

and urine specimens were collected before thia-

mm administration and before consumption of

the hospital diet. All patients were then treated

with 100 mg thiamin hydrochloride given paren-

terally on the day of admission and daily after-

wards until the patients were markedly im-

proved (1-8 weeks). This was followed by the

oral administration of 10-30 mg thiamin hydro-

chloride/day for another 2-4 weeks. Erythrocyte

transketolase activity and TPP effect were again

measured usually at 1 hr after thiamin admin-

istration (30 mm, 2 hr, or 24 hr, in some cases).

Urinary thiamin was determined at 24 hr after

thiamin administration.

The ETK activity was measured using Brin’s

technique (1) with the modifications of Bunce

and Sauberlich (8) and is expressed as the dis-

appearance of micrograms of pentose per gram

of hemoglobin in the hemolysate per hour of

TABLE I

Description of patients and types of beriberi

Sex Age Occupation

Unemployed

Carpenter

Unclnployed

Unemployed

Carpenter

21

2260

57

43

Patients

and typeof beriberi

�Vet

P1

P2

P3

p4

p5

P6

P7

P8

P9

plo

P11

Dry

P12

P13

P14P15

P16

P17

P18

P19P20

P21

M

M

M

M

M

M

F

F

M

M

M

M

M

M

M

F

F

M

M

M

M

18 Student

17 Factoryworker

15 Factory worker

50 Farmer

17 Student

48 Unemployed

17 Blacksmith

17 Jeweller

17 Farmer

18 Farmer

16 Trader

35 Trader

51 Shoemaker

20 Student

66 Farmer

15 �Vatch repairer

1018 Tanphaichitr et a!.

Nakorn -

pathom

Hau-Hin

Bangkok

Bangkok

Kanchana-

bun

Samut-

prakarn

Bangkok

Bangkok

Nontabuni

Thonburi

Thonburi

Bangkok

Bangkok

Non taburi

Chacherng-sao

Samutsak-

horn

Thonbuni

Bangkok

Bangkok

Suphanburi

Nakorn

Sawan

incubation. The TPP effect is expressed aspercent stimulation of the enzyme by addedthiamin pyrophosphate. The estimation of uri-nary thiamin excretion was done by the thio-

chrome method (9) and expressed as micrograms

of thiamin per gram creatinine (10).Both ETK activity and urinary thiamin ex-

cretion were also determined in 24 control Thai

subjects, age ranging from 21 to 40 years. Three

of them were physicians and the rest had vari-ous occupations. Routine physical examinations

and laboratory tests including blood examina-tion, urinalysis, electrocardiographic study, and

chest X-ray examination revealed normal find-

ings. Five subjects received 100 mg thiamin hy-

drochloride parenterally after the initial col-

lection of blood and urine samples. At 1 and 24

hr after thiamin injection, blood samples were

again drawn for ETK activity and TPP effect.

The biochemical tests also were performed

on 10 patients suffering from various other dis-

eases except beriberi, in order to establish the

specificity of thiamin treatment and to exclude

Residency the possibility that thiamin deficiency might

contribute to the presence of edema in patients

Ui to U7 and to the peripheral neuritis in U8

to UlO. These patients were treated with thia-

mm when first admitted to the hospital, but no

clinical improvement was observed. In various

cases, the diagnosis was established after further

investigations were performed. For instance, a

large amount of arsenic was detected in the

urine of patients U8, U9, and UlO.

RESULTS

Description of Patients and Dietary Habits

Table I shows age, sex, occupations, and

types of beriberi. During the period of this

study, patient P1 was admitted to the

hospital twice, 10 months apart. Fifty-four

percent of the patients were diagnosed as

having wet beriberi. Of interest, 76% of

the patients resided either in Bangkok,

the capital of Thailand, or within 50 km

from Bangkok; 62% of the patients were

under 25 years of age; and 29% were over

45 years. Their major source of food was

milled rice with small portions of cooked

fish and vegetables. Meat was occasionally

_________ consumed, except P7 and PS, who were

siblings, gave the history of pork consump-

tion for 1-2 weeks prior to their admission

to the hospital. Two patients, P12 and P13,

had changed from home-pounded glutinous

rice (Oryza glutinosa) to milled ordinary

rice (Oryza saliva), 1 and 2 months prior to

the onset of the disease, respectively. In re-

gard to the history of drinking alcohol, only

P11 had been a chronic alcoholic but he

had given up drinking 1 year prior to ad-

mission. Four patients (P17, P18, P20, and

P21) had received multivitamin injections

before admission to the hospital.

Clinical Manifestation

Two major systems, the cardiovascular

and nervous systems, were involved. Evi-

dence of peripheral neuritis was observed

Adult Beriberi 1019

both in wet and dry beriberi. The im-

portant signs that helped in diagnosing

beriberi were tenderness over the calf

muscles and difficulty in rising from the

squatting position. Hypesthesia of super-

ficial sensation (pain and touch) was pres-

ent in all except P13, P18, and P21,

whereas joint position and vibration senses

were affected in only P15, P16, P18,

and P21. Hyperesthesia of pain and touch

sensations was observed in P18. These

impaired! sensations disappeared after 7

days--I months of thiamin administration.

The time taken for the recovery from motor

weakness, which was observed in 12 out of

21 patients, (lid not exceed! 2 months.

Absent or hypoactive knee and ankle

jerks in 16 patients remained for months

after the treatment. Cardiovascular mani-

festations were observed only in wet ben-

i)eri. Edlema was present in all cases, but

congestive cardliac failure was seen only in

two patients.

The outstanding changes following

thiamin administration in wet beriberi

were:

1) Diuresis, which occurred within 24-

18 hr after the first (lose of thiamin. Total

body weight loss varied from 1.8 to 26.6

kg within a penio�1 of 3-15 days after

thiamin supplementation depending upon

tile severity of edema.

2) Gallop rhythm and pulmonary crepi-

tation noted in P1 and! P11 disappeared

within 48 hr.

3) Systolic and! diastolic blood pres-

sures rose in two cases within 24 hr. On

admission, blood pressures in P1 (1st and

2nd adlmissions) and P3 were 90/30, 160/

100, and 120/80 mm Hg, respectively.

After 24 hr of treatment, their blood pres-

sures rose to 100/50, 200/110, and! 180/120

mm Hg and returned to 120/80 and 150/

100 mm Hg 10 days later.

Two significant roentgenologic findings,

namely cardiomegaly and pulmonary con-

gestion, were frequently demonstrated in

the patients with wet beriberi. Eight of

eleven patients with wet beriberi ex-

hibited a cardiac-to-thoracic ratio of over

50% before the therapy. The ratio was

rec!uced under thiamin administration in

all but one subject. Nine of eleven pa-

tien ts demonstrated pulmonary congestion,

and, among these, two showed a small

amount of pleural effusion. These findings

disappeared within 1 month after thiamin

administration.

Abnormal electrocardiograms were

found only in wet beriberi. Eight of eleven

patients showed a prolonged Q-T inter-val averaging 0.45 sec. Three patients

showed relatively low voltages. Abnormali-

ties of the T waves in the precordial leads

were observed in seven patients. This con-

sisted! of flat or inverted T waves. More

pronounced inversion of the T wave in

the right precorc!ial leads were observed in

four cases during the recovery period. All

these abnormalities became normal within

40 days after thiamin administration.

BIOCHEMICAL STUDIES

Table II shows the mean values of

ETK activity, TPP effect, and urinary

thiamin excretion in 24 control subjects,

16 previously nontreated beriberi patients,

6 previously treated beribei-i patients, anti

another 10 patients suffering from various

diseases.

In control subjects, significant increases

in ETK activities were not observed at

1 hr after thiamin administration (P =

0.10) but they were demonstrated after

24 hr (P = 0.01). The mean TPP effect

was not affected significantly at 1 hr (P =

0.21) nor 24 hr (P = 0.15) after thiamin

administration.

Beriberi patients in this study could be

divided into two groups, namely, 16 pre-

viously, nontreated patients (P1-P6, P9-

P16, and P19) and six patients (P7, P8,

P17, P18, P20, and P21) treated prior to

admission to the hospital. The treated

group included those who had received

vitamin supplements or a thiamin-en-

riched d!iet before admission.

The mean ETK activity before thiamin

1020 Tanphaichitr et al.

TABLE II

Mean values of ETK, TPP, and urine thiarnin excretion in various groups,

before and after thiamin administrationa

b bu jectTime after

‘ g�i�en,

ETK activity, �sg pentose/gHb of hemolysate per hr

TPPeffect, %d

Urine thiamin,mg/g creatinine

NoTPP Plus TPP

Control

(24) 0 6,694 ± 507 7,104 ± 507 7.2 ± 2.1 0.07 ± 0.02

(5) 1 7,951 ± 1,151 8,350 ± 1,189 5.4 ± 1.3

(5) 24 8,849 ± 1 ,700 9,133 ± 1 ,806 2.7 ± 1 .2

Beriberi

(l6)#{176} 0 3,934 ± 732 5,327 ± 844 46.4 ± 6.4 0.15 ± 0.06

(16) 1 6,147 ± 809 6,330 ± 848 2.6 ± 0.7

(15) 24 6,262 ± 853 6,667 ± 859 7.6 ± 2.3 84.66 ± 12.17

Beriberi

(6)! 0 8,826 ± 1,301 9,182 ± 1,303 4.7 ± 1.9 0.17 ± 0.13

(5) 1-2 8,594 + 1,357 8,645 ± 1,342 0.9 ± 0.6

(6) 24 9,680 ± 1 ,461 9,728 ± 1 ,493 0.3 ± 0.3 101 .03 ± 25.98

Various diseases

(lO)o 0 12,613 ± 943 13,199 ± 943 5.0 ± 1.4 1.00 ± 0.51

Values are mean ± SE. P values are reported in the text. Numbers in parentheses indicate num-

bers of subjects. C Thiamin hydrochloride, 100 mg, given parenterally. d Thiamin pyrophosphate

effect expressed as percent stimulation of the enzyme in the presence of added thiamin pyrophosphate.

No treatment prior to hospital admission. / Previously treated with vitamins or enriched rice.

Iron-deficiency anemia (2), pellagra (1), nephrotic syndrome (I), cardiomyopathy (2), autoimmune

disease (1), and arsenical neuropathy (3).

administration of nontreated beriberi pa-

tients was significantly lower than that of

the control subjects (P = 0.02). When

comparisons were made within the same

group, ETK activities at 1 hr and 24

hr after thiamin administration were sig-

nificantly higher than the initial ETK ac-

tivity (P < 0.001 and P < OMO1, respec-

tively), but the mean value at 24 hr was

not significantly higher than the 1 hr

mean value (P = 0.46). Figure 1 shows the

fluctuation of the ETK activity from day

to day in this group of patients. All values

were higher than the initial level.

The mean TPP effect in nontreated

beriberi patients before thiamin adminis-

tration was significantly higher than that

of the control subjects (P < 0.001). Ex-

cept for subject P19, all exhibited TPP

effects greater than 16%. The TPP effect

at 1 hr was significantly lower than the

initial TPP effect (P < 0.001). Sequential

changes of TPP effect are presented in

Fig. 2. All values fell below 15% stimula-

tion after thiamin administration in spite

of the daily fluctuation in ETK activity.

Twenty-four hours after thiamin adminis-

tration, the urinary thiamin excretion was

increased to 84.66 ± 12.17 mg/g creati-

nine.

The means of ETK activity and TPP

effect of previously treated beriberi pa-

tients before thiamin administration were

not significantly different from those of

the control subjects (P = 0.28 and P =

0.27, respectively). Among the patients

themselves, the ETK activity observed! at

24 hr after thiamin administration was

significantly higher than the initial value

(P = 0.015), whereas the TPP effect was

significantly lower than the initial value

(P < 0.001). The mean urinary thiamin

excretion of the previously treated patients

before vitamin B1 injection in the hospital

2 3 4 5 7

Adult Beriberi 1021

was not significantly higher than that of

the control subjects (P = 0.06). At 24 hr

after thiamin administration, the urinary

thiamin excretion was 101.03 ± 25.98 mg/g

creatinine.

The means of ETK activity and urinary

thiamin excretion of the patients suffering

from other diseases were significantly

higher than those of the control subjects

(P < 0.001 and P < 0.001, respectively),

although no difference in the mean TPP

effect was observed (P = 0.52).

DISCUSSION

Sauberlich (11) has recently reviewed

the biochemical alterations in thiamin

deficiency and conduded that two bio-

chemical tests, namely urinary thiamin

excretion and erythrocyte transketolase

activity, should be performed in evaluating

the thiamin nutritional status. The study

of thiamin deficiency, based on transketo-

lase activity, has been done in experimen-

tal thiamin deficiency (1, 12), dry beriberi

(13), Wernicke’s encephalopathy (14-16),

tobacco-alcohol amblyopia (17), and six

cases of beriberi heart disease (18, 19). The

past studies were done mainly on patients

who were alcoholics.

In this study, data were obtained sug-

gesting that during thiamin deficiency the

coenzyme thiamin pyrophosphate was de-

creased in availability. This is evidenced

by the high TPP effect on ETK in non-

treated beriberi patients and the significant

reduction at 1 hr after thiamin adminis-

D69s

FIG. 1. Demonstrating erythrocyte transketolase activity in nontreated beriberi patients. The ETK activity

varies from one patient to the other and from day to day even in the same subject. Initial ETK activity was

consistently lower than the activity after thiarnin administration.

TABLE III

1022 Tanphaichitr et al.

The TPP effect in various groups of subjects

Subjects % TPP effect

Groups NumberAcceptable, Low, 16-20 Defic�nt,

Control 24 21 (88) 3 (12)

Nontreatcd 16 1 (6) 2 (13) 13 (81)

beriberi

Treated 6 6 (100)

beriberi

Various dis- 10 10 (100)

eases

Subjects were classified by Sauberlich’s criteria

(8). Numbers in the parentheses show percent of

subjects in each group.

tration in vivo, whereas no significant

difference in TPP effect before and after

thiamin administration in control subjects

could be demonstrated. The method for

transketolase determination used in this

study is similar to the method used by the

Interdepartmental Committee on Nutrition

fom National Defense (ICNND) survey con-

ducted in the Union of Burma (8), and

the criteria for evaluation are the same

as described by the ICNND. It has been

suggested that a TPP effect greater than

16% indicates thiamin deficiency. Our

(!ata substantiate this criterion, since 94%

of the samples from beriberi patients who

had not received previous treatment

showed a TPP effect in excess of 16%

(Table III). The results in Table II to-

gether with the value of TPP effect dur-

ing the recovery period of nontreated

beriberi patients (Fig. 2) show that a TPP

effect greater than 16% indicates thiamin

deficiency. A decrease in the mean TPP ef-

fect in the previously treatedi beriberi pa-

tients after thiamin injection might indicate

that the previous vitamin supplementation

or enriched thiamin diet received was in-

Adult Beriberi 1023

sufficient to maintain a maximum transke-

tolase activity.

In 1964, Brin reported that the ETK

stimulation by thiamin pyrophosphate in

vitro of thiamin-deficient subjects could be

reduced to a normal range within 2 hr

after parenteral administration of the vita-

min (13). In this study, the mean TPP

effect of the nontreated beriberi patients

at 1 hr after thiamin administration was

found to be reduced significantly from the

initial value (P < 0.001). In two cases, this

decrease occurred within 30 mm after vita-

min injection (Fig. 2).

Baker (20) in 1967 presented the follow-

ing observations concerning ETK activity.

In normal persons, no increase in the

ETK activity was observed when thiamin

pyrophosphate was added to the erythro-

cyte hemolysate, whereas in thiamin-de-

ficient subjects, three patterns of changes

were observed:

1) An increase in the ETK activity was

noted a) when thiamin pyrophosphate was

added in vitro but no thiamin adminis-

tered in vivo and b) without the addition

of thiamin pyrophosphate in vitro but

after thiamin administration in vivo.

2) In those who had an impaired phos-

phorylation of administered thiamin, the

ETK activity increased only in the pres-

ence of exogenous thiamin pyrophosphate

that was added to erythrocyte hemolysate,

hut thiamin administration in vivo did not

influence the level of the ETK activity.

3) No change in ETK activity was ob-

served either after thiamin administration

in vivo or after the addition of thiamin

pyrophosphate in vitro.

In some cases the enzyme activity re-

turned to normal after positive nitrogen

balance was restored, so the defect might

be due to a decreased level of the apoen-

zyme itself. This was observed in subjects

with liver diseases.

In this study, the mean ETK activity

significantly increased both after the ad-

dition of thiamin pyrophosphate to the

erythrocyte hemolysate before thiamin

administration and at 1 hr after thiamin

administration in vivo (P < 0.001). This

might indicate that the transketolase co-

enzyme was not available in these patients

during thiamin deficiency. This is con-

firmed by the low level of ETK activity

of nontreated beriberi patients when com-

pared with that of control subjects (P =

0.02).

In 1964, Brin showed that the ETK ac-

tivity was low in every thiamin-deficient

patient studied, whereas 2 hr after thiamin

administration in vivo the ETK activity

was equivalent to the initial blood sample

incubated with thiamin pyrophosphate

(13). The results of our study showed that

the initial ETK activity in every nontreated

beriberi patient was low, but at 1 hr after

thiamin administration, the ETK activity

in the absence of added thiamin pyrophos-

phate was equivalent or higher than that

observed when the initial blood sample was

incubated with thiamin pyrophosphate.

In six patients, the ETK activity at 1 hr

was greater than the value obtained when

thiamin pyrophosphate was added in

vitro to the zero time sample. This occur-

rence could probably be explained by the

reason that a) the amount of thiamin py-

rophosphate added in vitro (15.4 /Lg/ml

of initial assay tube volume) may not be

sufficient to compensate for the amount

depleted in vivo, or b) the mechanism of

binding between the apotransketolase en-

zyme and the coenzyme thiamin pyrophos-

phate is more effective in vivo.

Further investigation is needed before

decisive conclusions relative to mechanisms

can be drawn. A significant increase in

the ETK activity at 24 hr after thiamin

administration when compared with the

initial ETK activity in the control sub-

jects, nontreated beriberi patients, and

treated beriberi patients may be due to a

true increase in the ETK activity or a

natural fluctuation as Dreyfus reported

(15). Ow- results could be explained by

As the mean civilian ii:take is 0.24

1024 Tanphaichitr et a!.

the latter reason as is evidenced by the

fluctuation level of ETK activity from

day to day (Fig. 1). In 1965, Brin et a!.

(21) and Dibble et al. (22) reported that a

low ETK activity was not always corre-

lated with a high TPP effect. This was

also observed in this study.

Although the measurement of urinary

thiamin is a useful criterion for a survey

of a large population, it is subject to cer-

tain errors when applied to individuals,

as is evidenced by the results of this study.

The Manual for Nutrition Surveys (9)

suggests that urinary thiamin of less than

65 �g/g creatinine excretion be considered

indicative of low or deficient thiamin

status. Seventy-one percent of our control

subjects fell in this low or deficient range,

yet appeared in good clinical condition.

Thus, thiamin excretion alone is not a

good criterion for thiamin nutrition status

in an individual subject. Also, fluorescent

materials often are excreted in the urine,

making an accurate thiamin determination

difficult. In 1954, Suzawa (23) observed

high urinary thiamin excretion in some

cases of thiamin-deficient patients de-

spite the presence of a low blood thiamin

and clinical manifestation. He suggested

TABLE IV

Urinary thiamin excretion in various

groups of subjects

SubjectsUrinary thiamin excretion,

Mg/g creatinine

Groups Number High,>130

Accept-able,66-129

Low,27-65

Deficient,<27

Control

Nontreated

beriberi

Treated

beriberi

Various dis-

eases

24

15

6

10

4(17)

3 (20)

1 (17)

6 (60)

3 (13)

1 (7)

1 (17)

1 (10)

6(25)

3 (20)

4 (66)

11(45)

8 (53)

3 (30)

Subjects were classified by criteria designated

by ICNND. Numbers in the parentheses show per-

cent of subjects in each group.

that this was due to a disturbance in the

utilization of the ingested thiamin. This

was also observed in this study (Table iv).

No correlation between urinary thiamin

excretion and TPP effect could be de-

tected. These results agreed with the re-

ports of Brin et al. (21) and Tripathy

(24). From these results, it is possible to

propose that the TPP effect is a more

specific test for judging thiamin adequacy

than the measurement of the urinary thia-

mm.

In general, the clinical manifestations of

beriberi in the present study are not dif-

ferent from previous reports (25-27).

Transient hypertension during the re-

covery period of P1 (second admission),

and P3 could be probably due to the in-

crease in total peripheral resistance. In

1942, Garland and McKenny (28) reported

that the enlarged heart shrank about 3

cm in its total transverse diameter in a

period of 10 (lays on thiamin therapy.

This magnitude of change was observed

only in P1 and P2. However, there was

some decrease in cardiac size observed in

most patients after thiamin administration.

The results of the electrocardiographic

studies are in agreement with Pallister

(29) who showed no difference between

Occidental and Oriental beriberi. Al-

though the pattern of electrocardiographic

change was rather uniform, it cannot be

considered specific to beriberi.

It is well known that beriberi has been

commonly found among rice-eating popu-

lations. The results of the ICNND sur-

vey in Thailand in 1960 (6) revealed that

the mean intake of vitamin B1 among

civilians was 0.24 mg/ 1,000 kcal with little

variation from area to area. The Thai

soldier received more thiamin, 0.28 mg/

1,000 kcal, than the civilians because the

Thai service man consumed undermilled

rice. Thiamin excretion in the urine cor-

related moderately well with thiamin in-

take.

Adult Beriberi 1025

mg/l,000 kcal one can conclude that the

national picture is one of marginal thia-

mm intake. Thai people generally con-

sume machine-milled rice, which contains

less thiamin than undermilled or home-

pounded rice. Furthermore, a consi!erable

amount of thiamin also is lost by dis-

carding the water after soaking and boil-

ing the rice. It was estimated that about

85% of the vitamin is lost by this method

of cooking (30). The thiamin intake was

not estimated in our patients, but the

dietary histories revealed that all of the

beriberi patients consumed the usual Thai

diet, as described by Bisolyaputra (4) and

the ICNND survey (6), and they cooked

their rice as described previously.

It is also possible that some thiamin is

destroyed in Thai foods because of the

enzyme, thiaminase, which is present in

some fish and vegetables that are con-

sumed!. This enzyme has been found in

fish and vegetables obtained from North

and Northeast Thailand (31, 32). The

role of thiaminase in the etiology of beri-

beri of these patients requires further

study.

SUMMARY AN!) CONCLUSIONS

Twenty-one adult patients were clini-

cally diagnosed as having beriberi and

were studied to determine whether a cor-

relation existed between the biochemical

tests, including urinary thiamin excretion

ant! erythrocyte transketolase activity, and

clinical manifestations of the disease.

The best criteria for diagnosis of thia-

mm deficiency included:

1) Specific response to thiamin adminis-

tration. The improvement appears faster in

wet than in dry beriberi. The outstanding

changes following thiamin administration

in wet beriberi are a) diuresis, which ap-

pears within 24-48 hr; b) decrease in heart

rate and increase in blood pressure, which

may appear within 12 hr; and c) reduction

in cardiac size as well as clearing of the pul-

monary congestion with the normaliza-

tion of electrocardiogi-ams. It is difficult to

use the response to thiamin administration

as a criterion for immediate diagnosis in

dry beriberi because more time elapses be-

fore improvement is observed.

2) Biochemical tests that include erythio-

cyte transketolase (ETK) activity and thia-

mm pyrophosphate (TPP) effect. The

TPP effect is a good index for judging

thiamin deficiency in man. Generally, a

value greater than 16% can indicate a

deficient state. Reduction of the TPP ef-

fect appears within 1 hr after thiamin in-

j ection. Previous vitamin supplementation

and intake of an enriched thiamin diet

must be considered in the interpretation

of TPP effect. The normal level of ETK

activity cannot be established due to a

great variation of the value in control

subjects. However, the increase in ETK

activity from an initial low value together

with a high percent stimulation on TPP

can be used to measure the thiamin ade-

quacy in man. The TPP effect is a better

index than urinary thiamin excretion for

diagnosing beriberi; however, thiamin ex-

cretion may be a useful criterion foi- a

survey study in a large population group.

The authors wish to express their appreciation

to Paul Gyorgy, M.D. for his enthusiastic support of

this study. We are deeply grateful to Robert Van

Reen, Ph.D., Howerde Sauberlich, Ph.D., and

William J. Darby, M.D., Ph.D. for their help in

reviewing the manuscript. We are indebted to the

interns, residents, and medical staffs of Siriraj Hos-

pital for their cooperation in sending these patients

to us. Finally, we wish to acknowledge the techni-

cal help of Miss Pa-nga Viriyapanich, B.S. in the

laboratory.

REFERENCES

I. BRIN, M., M. TA!, A. S. OSTA5HEVER AND H.KALINSKY. The effect of thiamine deficiency on

the activity of erythrocyte hemolysate transketo-

lase. I. Nutr. 71: 273, 1960.

2. BRIN, M. Erythrocyte transketolase in early

thiamine deficiency. Ann. N. Y. Acad. Sci. 98:

528, 1962.

3. BRIN, M. Thiamine deficiency and erythrocyte

metabolism. Am. J. Gun. Nutr. 12: 107, 1963.

4. BISOLYAPUTRA, U. Nutrition Activities in Thai-

1026 Tanphaichitr et a!.

uaizd-Past and Present. 1930-1959. Bangkok,

Thailand: Ministry Public Health, Nutr. Div.,

1959.

5. KLERKS, J. V. Final report on nutrition in Thai-land. WHO Regional Office for Southeast Asia.

(WHO Project: Thailand 36). SEA/Nutr./5,

March, 1959.

6. Interdepartmental Committee on Nutrition for

National Defense. Nutrition Survey-The King-

dom of Thailand (1960). Washington, D.C.:

U.S. Govt. Printing Office, February, 1962.

7. VALYASEvI, A., S. LOCHAYA, R. A. OLsoN AND

C. KAMPANAT-SANYAKORN. Epidemiological, clin-

ical and biochemical studies of beriberi in in-

fants and adults in Thailand. Ann. Progr. Rept.

SEA TO Med. Res. Lab., Clin. Res. Ctr. Bangkok,

Thailand, 1965.8. Interdepartmental Committee on Nutrition for

National Defense. Nutrition Survey-Union of

Burma. Washington, D.C.: U.S. Govt. Printing

Office, May, 1963, p. 163-167.

9. Interdepartmental Committee on Nutrition for

National Defense. Manual for Nutrition Surveys

(2nd ed) Washington, D.C.: U.S. Govt. Printing

Office, 1963.

10. Technicon AutoAnalyzer. Chauncey, New York:

Technicon Instruments Corp., 1963.

11. SAUBERLICH, H. E. Biochemical alterations in

thiamine deficiency-their interpretation. Am.

j. Clin. Nutr. 20: 528, 1967.

12. BRIN, M., S. S. SHOHET AND C. S. DAVIDSON. Theeffect of thiamine deficiency on the glucose

oxidative pathway of rat erythrocytes. I. Biol.

Chem. 230: 319, 1958.

13. BRIN, M. Erythrocyte as a biopsy tissue in the

functional evaluation of thiamine deficiency.

1. Am. Med. Assoc. 187: 762, 1964.

14. WOLFE, S. J., M. BRIN AND C. S. DAVIDSON. The

effect of thiamine deficiency on human erythro-

cyte metabolism. J. Gun, invest. 37: 1476, 1958.

15. DREYFUS, P. M. Clinical application of blood

transketolase determinations. New Engl. I. Med.

267: 596, 1962.

16. BURCENER, M., AND P. G. JURGENS. Thiamine ex-

cretion and transketolase activity in chronic

alcoholism and Wernicke’s encephalopathy.

German Med. Monthly 12: 396, 1967.

17. DREYFU5, P. M. Blood transketolase levels in

tobacco-alcohol amblyopia. Arch. Ophthalmol.

74: 617, 1965.

18. AKBARIAN, M., N. A. YANKAPOULE5 AND W. H.

ABELMAN. Hemodynamic studies in beriberi

heart disease. Am. 1. Med. 41: 197, 1966.

19. AKBARIAN, M., AND P. M. DREYFU5. Blood trans-ketolase activity in beriberi heart disease. J.

Am. Med. Assoc. 203: 77, 1968.

20. BAKER, H. Symposium: Advances in the detec-tion of nutrition deficiencies in man (discussion).Am. J. Clin. Nutr. 20: 543, 1967.

21. BRIN, M., M. V. DIBBLE, A. PEEL, E. MCMULLEN,

A. BOURQUIN AND N. CHEN. Some preliminary

findings in the nutritional status of the aged in

Onondaga County, New York. Am. J. Gun. Nutr.

17: 240, 1965.

22. DIBBLE, M. V., M. BRIN, E. MCMULLEN, A.

PEEL AND N. CHEN. Some preliminary biochemi-

cal findings in junior high school children in

Syracuse and Onondaga County, New York. Am.

I. Clin. Nutr. 17: 218, 1965.

23. Review of Japanese Literature on Beriberi and

Thiamine, edited by N. Shimazono and E.

Katsura. Vitamin B Res. Comm. Japan, Clin.

Nutr. Fac. Med. Kyoto: Kyoto Univ., 1965, p.

66.

24. TRIPATHY, K. Red cell transketolase activity for

evaluation of thiamine adequacy. Federation

Proc. 25: 671, 1966.

25. Review of Japanese Literature on Beriberi and

Thiamine, edited by N. Shimazono and E.

Katsura. Vitamin B Res. Comm. Japan, Clin.Nutr. Fac. Med. Kyoto: Kyoto Univ., 1965, p.

29-78.

26. WILLIAMS, R. R. Toward the Conquest of Beri-

beri. Cambridge, Mass.: Harvard Univ. Press,

1961, p. 53-80.

27. BEATON, G. H., AND E. W. MCHENRY. Nutrition.

New York: Academic, 1964, vol. II, pp. 128-133.

28. GARLAND, L. H., AND A. C. MCKENNY. The

roentgen diagnosis of vitamin deficiency cardiac

conditions with some clinical observations on

thiamine deficiency. Radiology 38: 426, 1942.

29. PALLISTER, R. A. Electrocardiogram in Oriental

beriberi. Trans. Roy. Soc. Trop. Med. Hyg. 48:

490, 1954.

30. TMANGRAK5ATVE, S., AND S. SRISUKH. Thiamine

in Thai rice. J. Pharmn. Assoc. Thailand 8: 8,

1955.

31. LOCHAYA, S. Possible role of thiaminase in the

etiology of beriberi in Thailand. Ann. Progr.

Rept. SEA TO Med. Res. Lab., Clin. Res. Ctr.

Bangkok, Thailand, 1966, p. 288.

32. SREEVANICH, T., B. PHORNPHIBOUL AND F. W.

DUNN. Thiaminase activity of some edible fresh

water animals and fishery products of Thailand.

J. Med. Assoc. Thailand 51: 664, 1968.