Experimental Thiamin Deficiency in Man and Measurement of Thiamin Status

In young and healthy nonalcoholic subjects, subjective symptoms appear after 2 or 3 weeks of deficient diet but urinary thiamin will already be falling (Table 3). Characteristic early symptoms include anorexia, weakness, dysthesiae, and depression. At this stage, urinary thiamin will be almost zero, ETKL activity depressed, and the TDP effect approximately 15-30%. After 6-8 weeks the only objective signs at rest may be a slight fall in blood pressure and moderate weight loss, although urinary thiamin will now be negligible and the TDP

Table 3 Effects of thiamin deficiency on urinary thiamin, the erythrocyte transketolase TDP effect, and early clinical symptoms of thiamin deficiency in human volunteers

Days of

Urinary thiamin

TDP

Clinical signs of deficiency following diets containing 150-350pg thiamin/dayb

deficiency

fag/day)a

effect (%)a

5

50

0-10

Mostly studies report no signs but one study (360 mg/day) found within 1 week chest

10

25

~15

pains, extreme lassitude, anorexia, palpitation, and burning feet

21-28

<25

~30

Loss of body weight, anorexia, general malaise, insomnia, increased irritability,

fatigue on slightest exertion

30-40

Negligible

>40

Increased malaise, loss of body weight, intermittent claudication and polyneuritis,

bradycardia, peripheral oedema,a cardiac enlargement,a ophthalmoplegia

>45

10-20

>40

Additional signs of nausea and dizziness appeared

~75

10-20

Additional signs of vomiting, low blood pressure, and tenderness of calves

aBiochemical data and report of oedema and cardiac enlargement from Brin (1964), in which healthy male medical students were fed 200 mg thiamin per day for 6 weeks. TDP effect is a measure of thiamin status obtained by measuring the activity of erythrocyte transketolase in the presence and absence of added thiamin diphosphate.

bClinical signs adapted from several studies. Investigators were impressed by the rapid degree of debility induced by the specific withdrawal of thiamin from the diet. In one group (150 mg/day for 75 days, four female mental patients), the authors reported that the condition more closely resembled 'neurasthenia' than beriberi and noted that oedema, cardiac dilation, and peripheral pain characteristic of classic beriberi were all absent (reported by Carpenter, 2002).

aBiochemical data and report of oedema and cardiac enlargement from Brin (1964), in which healthy male medical students were fed 200 mg thiamin per day for 6 weeks. TDP effect is a measure of thiamin status obtained by measuring the activity of erythrocyte transketolase in the presence and absence of added thiamin diphosphate.

bClinical signs adapted from several studies. Investigators were impressed by the rapid degree of debility induced by the specific withdrawal of thiamin from the diet. In one group (150 mg/day for 75 days, four female mental patients), the authors reported that the condition more closely resembled 'neurasthenia' than beriberi and noted that oedema, cardiac dilation, and peripheral pain characteristic of classic beriberi were all absent (reported by Carpenter, 2002).

effect >35%. After 2 or 3 months, apathy and weakness become extreme, calf muscle tenderness develops, and there is loss of recent memory, confusion, ataxia, and sometimes persistent vomiting. Urinary thiamin will be negligible and the TDP effect may be normal (because apo-ETKL is unstable even in vivo), but ETKL activity should be considerably depressed.

The clinical symptoms resulting from experimental thiamin deficiency in man have usually responded rapidly to treatment with thiamin. In one feeding study, however, two mental patients were kept for 110 days on a diet providing 200 mg thiamin daily and 1 mg of thiamin by injection 1 day each week; thus, their overall weekly average was 350 mg/day. They developed a polyneuropathy characterised by defects in the sensory nervous pathways, loss of tendon reflexes, and paralysis of the legs, which took many weeks to respond to large doses of thiamin, and in one case response was still incomplete after 4 months of treatment. The slow cure suggested that degeneration of peripheral nerves had occurred, as is indicated in the dry form of beriberi, in which the neurological lesions are irreversible.

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