The acute phase response and vitamin A status in malaria.

Plasma retinol and 5 carotenes were assayed by high performance liquid chromatography in Thai rural and urban malaria patients and matched control subjects. Plasma retinol was lower in the rural than in the urban controls and both groups of malaria patients had lower serum retinol concentrations than their respective controls. 29% (6/21) of the rural patients were biochemically deficient in retinol (less than or equal to 0.35 mumol/litre), suggesting severely depleted liver stores of vitamin A. The carotene data suggest that the intake of total carotenoids may be 50 to 100% greater than in the UK and that a much higher proportion of dietary beta-carotene is converted to vitamin A than in British adults. The concentrations of non-pro-vitamin A carotenoids in both groups of malaria patients were not compatible with vitamin A deficiency. The differences between patient and control median concentrations of pro-vitamin A (PVA) carotenoids were greater than those of non-PVA carotenoids, suggesting increased utilization of vitamin A in malaria. There was no evidence of clinical vitamin A deficiency in either of the communities studied; therefore, severely depleted stores of retinol are very unlikely. There is an alternative explanation for low plasma retinol levels in malaria patients because retinol is bound to the negative acute phase proteins, retinol binding protein and transthyretin. We suggest that the behaviour of retinol during infection indicates a rapid distribution into extravascular fluids and an increased availability to the tissues; i.e., it may be another beneficial effect of the acute phase response.

Influence of malaria infection on peroxyl-radical trapping capacity in plasma from rural and urban Thai adults.

Measurement of peroxyl-radical trapping capacity (TRAP) were made in plasma from patients with malaria from a rural and an urban Thai community. The results were compared with those from control subjects living in the same areas and chosen to match the patients closely. Measurements were also made of various antioxidants including nutritional indices vitamin C and alpha-tocopherol and the non-nutritional indices urate and protein-sulphydryl. Parasite counts, temperature on examination and the duration of illness were recorded together with measurements of plasma caeruloplasmin (EC 1.16.3.1), retinol and malondialdehyde (MDA). In general, most measurements made in the villagers were lower than those in the comparable urban groups. The exceptions were caeruloplasmin and MDA when the latter was expressed as MDA:cholesterol ratio. TRAP values were extremely low in 50% of the villagers and 25% of the urban patients with malaria and these results correlated with retinol and vitamin C and inversely with malonaldehyde. The results suggested that low TRAP values are associated with lipid peroxidation and that vitamin C and possibly retinol may be destroyed by the oxidative conditions present in the plasma in this disease.

Oral contraceptives: effect of long-term use on liver vitamin A storage assessed by the relative dose response test.

Vitamin A status measured by the relative dose response (RDR) test was determined among groups of Northern Thai women who had used estrogen-containing oral contraceptives (OCs) with or without multivitamin supplements through 13 cycles. Mean serum vitamin A values were elevated approximately 40% above those of control subjects (intrauterine contraceptive device (IUCD) users) during OC usage. Daily (one capsule) or periodic (two capsules 7 d/mo) multivitamin supplementation that included 1700 micrograms vitamin A per capsule did not significantly influence vitamin A serum values. The RDR test after 13 cycles was elevated in one individual who had taken OCs and the periodic multivitamin supplement. It reverted to normal after supplementation with vitamin A. A single high-dose vitamin A supplement (68,000 micrograms) did not change circulating levels of the vitamin. Among this population there is little evidence that use of estrogen-containing OCs for greater than 1 y resulted in a physiologically significant deterioration of vitamin A status.

PIP: Vitamin A status measured by the relative dose response (RDR) test was determined among groups of Northern Thai women who had used estrogen- containing oral contraceptives (OCs) with or without multivitamin supplements through 13 cycles. Mean serum vitamin A values were elevated approximately 40% above those of control subjects (IUD users) during OC usage. Daily (1 capsule) or periodic (2 capsules 7 days/month) multivitamin supplementation that included 1700 mcg vitamin A/capsule did not significantly influence vitamin A serum values. The RDR test after 13 cycles was elevated in 1 individual who had taken OCs and the periodic multivitamin supplement. It reverted to normal after supplementation with vitamin A. A single high-dose vitamin A supplement (68,000 mcg) did not change circulating levels of the vitamin. Among this population there is little evidence that use of estrogen-containing OCs for more than 1 year resulted in a physiologically significant deterioration of vitamin A status.

A direct assay for pyridoxal 5'-phosphate using pig heart apo-aspartate transaminase.

The development of a simple enzymatic method for the determination of blood and plasma pyridoxal 5'-phosphate (PLP) using pig heart apo-aspartate transaminase (apo-AST) is described. The technique requires three steps: sample extraction using perchloric acid, a binding step in which PLP in the sample extract is attached to the apo-AST and the enzymatic assay of the reconstituted holo-AST. PLP extracts were analysed with and without a known concentration of added PLP to correct for variation in recovery between different specimens. Procedures are outlined for manual and automatic analysis of the PLP extracts. Using the KONE Clinical Analyser after the extraction step, it is possible to measure enzyme activity in 100 specimens (i.e. 400 tubes) in a 5 h period. Results are shown from 185 healthy women aged 20-45 years, in which plasma PLP concentrations ranged from 5 to 165 nmol/L, and 142 men and 56 women in government service aged 17-64 years, whose plasma PLP ranged from 8 to 169 nmol/L. Values less than 20 nmol/L are believed to indicate vitamin B6 deficiency and the method is able to measure 5 nmol/L.

Impact of hormonal contraceptives vis-à-vis non-hormonal factors on the vitamin status of malnourished women in India and Thailand. World Health Organization: Special Programme of Research, Development and Research Training in Human Reproduction. Task Force on Oral Contraceptives.

The effects of combined oral contraceptives containing 30 or 50 micrograms ethinyl oestradiol and 150 micrograms levonorgestrel or a 3-monthly injectable preparation depo-medroxyprogesterone acetate (DMPA) on the vitamin status of low-income group women from two urban centres in India (Bombay and Hyderabad) and one rural centre in Thailand (Chiang Mai) were examined in a follow-up study over a period of 1 year. The magnitude of malnutrition in the study population vis-à-vis a middle-income reference group was assessed by comparing the baseline data on the two groups. Effects of time-related variables such as lactation and season were also examined by a cross-sectional analysis of the baseline data on the study population. In all three centres the majority of the study population suffered from biochemical riboflavin and/or pyridoxine deficiency even before initiating contraception. Lactation appeared to have an effect on the vitamin status, which varied among the different populations. Seasonal effects were seen, but showed inconsistent trends in the three centres. Both the oral contraceptive pills and DMPA tended to increase serum vitamin A and blood folate. The thiamin, riboflavin and pyridoxine status of the women who were already deficient did not deteriorate further with the use of hormonal contraception, as judged by enzyme saturation tests. Some deterioration in the riboflavin status of the normal women of Hyderabad was seen with the use of oral pills. Women who were biochemically deficient prior to the use of oral contraceptives tended to show some improvement in B-vitamin status, over the 1-year period of hormonal contraception.

Plasma pyridoxal 5'-phosphate in women with the premenstrual syndrome.

Measurements of plasma pyridoxal 5'-phosphate (PLP) were made in 210 healthy premenopausal women, and related to their experience of the premenstrual syndrome (PMS). The 41 women (20 per cent) who had moderate or severe PMS were compared with 95 women (45 per cent) with no, or only slight, premenstrual symptoms: the former group were older and were more likely to have children, but there were no significant differences in smoking habits or mode of contraception. Plasma PLP values were similar in the two groups (mean values with s.d. 39.59 +/- 22.95 and 40.56 +/- 23.33 nmol/l respectively). We conclude that pyridoxine status, as measured by plasma PLP levels, is not altered in women with PMS and that pyridoxine deficiency is unlikely to contribute to the occurrence of this syndrome.

Vitamin metabolism and the effects of multivitamin supplementation in oral contraceptive users.

The effect of combined oral contraceptives containing 158 micrograms of levonorgestrel and 38 micrograms of ethinyl estradiol on vitamin B-1, B-2, B-6, B-12, folates, vitamin A, carotenoids, vitamin E and tryptophan load test was studied in a group of 34 healthy non-lactating women. This was compared to an identical study conducted in another group of 19 subjects who used IUCDs for contraception, and also in two other groups of subjects who were given an additional multivitamin preparation on a daily basis (33 subjects) and on the days when OC was not taken (29 subjects). Assessments were made prior to, and during the third week of the 4th, 7th and the 13th cycles of OC treatment. Urinary xanthurenic acid excretion (XA), plasma vitamin A and the folate content of the sera and red blood cells were significantly increased by OC treatment, although this excessive XA excretion was adequately corrected with 18 mg of daily vitamin B-6 supplementation. The metabolism of the rest of the vitamins was not significantly altered by OC usage. This suggests that a routine use of multivitamin supplement may not be necessary.

Effects of medroxyprogesterone acetate on serum lipids, protein, glucose tolerance and liver function in Thai women.

Proteins (total, albumin, globulin and their subfractions), carbohydrate (intravenous glucose tolerance test), lipids (serum cholesterol, triglycerides and phospholipids), and liver function tests (alkaline phosphatase, lactic dehydrogenase and aspartate aminotransferase activities in the serum, bromsulphathalein retention test and serum bilirubin) were studied in 12 non-lactating healthy Thai subjects before, and subsequently at 3 weeks and 3, 6, 9 and 12 months after the initiation of treatment with injectable medroxyprogesterone acetate (150 mg I.M. every 90 days). Serum protein and lipid levels, and the results of liver function and I.V. glucose tolerance tests, remained unchanged in all subjects throughout the one-year study period. However, a significant and persistent increased insulin level was noted in all subjects, after initiation of the hormone treatment, during the first thirty minutes of intravenous glucose load. It is concluded that injectable medroxyprogesterone acetate used as a contraceptive agent does not interfere with glucose tolerance, lipid and protein metabolism, and that the liver function remains normal during its administration.

PIP: Total proteins (albumin, globulins and their fractions); carbohydrate (intravenous glucose tolerance); lipid (serum cholesterol, triglycerides, and phospholipids); and liver functioning (alkaline phosphatase, lactic dehydrogenase, and aspartate aminotransferase activities in serum, bromsulfathalein retention, and serum bilirubin); were assayed in 12 Thai women who were not lactating. The tests were performed before, and 3 weeks, 3,6,9, and 12 months after the advent of treatment with medroxyprogesterone acetate (DMPA), which was injected intramuscularly in 150-mg doses every 90 days. Triglyceride concentration was unchanged overall; however, mean fasting triglyceride concentration on Day 20 decreased significantly when compared with Day -33 pretreatment control (P .025). A significant increase ( P .01) in mean fasting cholesterol was demonstrated on Day 20; this, however, was thought to be caused by the high dietary lipid intake during hospitalization rather than an effect of the DMPA. In general, serum protein and lipid levels, and liver function and glucose tolerance, remained unchanged over 1 year. There was, however, a significant and persistent increase in insulin level in all subjects after initiation of hormone treatment during the first 30 minutes of intravenous glucose load. The study concludes that DMPA does not interfere with glucose tolerance, lipid and protein metabolism, or liver function during its administration.