Quantitative significance of measuring trimethylselenonium in urine for assessing chronically high intakes of selenium in human subjects

The purpose of the present study was to investigate the effects of Se restriction on the excretion of Se in men who had consumed high levels of this element during their entire lives. With the use of stable isotopes of Se as selenite, the excretion of methylated Se in urine was investigated in Chinese men (n 10) who had habitual chronic high intakes of this element. The relationship between either urine Se or trimethylselenonium (TMSe) to the estimated long-term Se intake was not linear over the entire range of intake, which was also true for the infusion of labelled selenite. A non-linear relationship was also found between urine TMSe and urine Se both for TMSe arising from catabolism of endogenous body Se and that from infused selenite. The data suggest a close precursor-product relationship of urine Se and its TMSe component based on the nearly identical specific activities for these two selenocompounds. Although dimethylselenide in breath was not measured in the present study, combining urinary TMSe with this breath test may be more useful in the assessment of long-term Se status.     

Absorption, distribution and excretion of selenium from beef and rice in healthy North American men

Previous metabolic studies of selenium used pure selenium compounds with pharmacologic activities unrelated to selenium nutrition. Healthy men were fed foods naturally high or low in selenium while confined to a metabolic research unit. Selenium intake was 47 microg/d (595 nmol/d) for 21 d while energy intakes and body weights were stabilized and selenium excretion and intake came into metabolic balance. On d 22, selenium intake was changed to either 14 microg/d (177 nmol/d, low selenium) or 297 microg/d (3.8 micromol, high selenium) for the remaining 99 d. The absorption, distribution and excretion of selenium in food were similar to selenomethionine, and distinctly different from sodium selenite. Daily urinary selenium excretion and selenium concentrations in plasma and RBC showed the largest responses to selenium intake relative to interindividual variation. Urinary selenium and plasma selenium responded most rapidly to changes in selenium intake, whereas RBC reflected longer-term selenium intake. Given the difficulty of 24-h urine collections outside a metabolic research unit, RBC and plasma selenium seem to be the most useful indicators of selenium intake. During the intervention period, the high selenium group retained 15 mg (190 micromol) of selenium, with approximately 5 mg (63 micromol) going into skeletal muscle. The low selenium group lost only 0.9 mg (11 micromol) of whole-body selenium but lost 3.3 mg (42 micromol) from muscle, indicating that selenium was redistributed from muscle to tissues that have a higher metabolic priority for selenium such as testes. Fecal excretion decreased by half, representing an important but previously underappreciated adaptation to selenium restriction.     

Kinetics of a single administration of 74Se-selenite by oral and intravenous routes in adult humans

The purpose of this study was to explore the fate of a single dose of labeled selenium as determined by its route of administration. Thus, the appearance of a stable isotope of selenium, administered as 74-Se-selenite, was measured in plasma, urine, and feces, with neutron activation analysis, following a 81.7 micrograms dose of 74Se-selenite given either intravenously or orally in two groups (n = 4) of healthy, young adult men, who were otherwise maintained on a diet providing a constant and adequate selenium intake. From these isotopic data, measurable parameters of urine excretion, total body retention and selenite-exchangeable metabolic pool (Se-EMP) were defined to provide a quantitative assessment of selenium metabolism in these subjects. The initial 24-hr urine excretion of the label was higher for the intravenously administered label (18.2 +/- 2.1% of dose) compared to the oral dose (11.7 +/- 2.6% absorbed dose). Thereafter, the excretion of isotope was the same for both groups. For equivalent entry of Se into the body, measured total body retention and Se-EMP were the same for both groups. These initial kinetic data suggest that the overall utilization of selenium from a single administration of selenite is comparable for the two routes of intake and that the host's selenium requirement can probably be met adequately via the intravenous administration of selenite.     

Kinetic modeling of selenium metabolism in nonpregnant ewes

The kinetics of selenium metabolism in three nonpregnant ewes were studied by the intravenous injection of 75Se-sodium selenite and measurement of radioactivity responses in blood, tissues and excreta. Stable selenium measurements were also made to determine selenium intake, excretion in feces and urine, and mass of selenium in tissues. Immediately following tracer injection, there was a rapid disappearance of radioactivity from plasma reflecting the uptake of the element by the liver and blood cells. The decrease in plasma radioactivity ceased abruptly by 30-45 min, and was followed by an increase to a peak by 3-4 h and a more gradual biphasic decline thereafter. A kinetic model of selenium metabolism in the whole animal was constructed employing the SAAM/CONSAM computer program. The multiphasic response of plasma radioactivity during a physiological steady state was explained on the basis of rapid hepatic uptake of selenium and its subsequent reappearance in the circulation in protein-bound form followed by further metabolism and excretion of the element. The model provides reference parameter values for 75Se-sodium selenite kinetics in selenium-replete, mature nonpregnant ewes for comparison with the kinetics in animals whose selenium status may be altered.     

Dose-response relations in urinary excretion of trimethylselenonium in the rat

75Se-labeled selenite was administered to fasting rats by orogastric intubation (1.5-3000 micrograms/kg body wt). Urine was collected and characterized for total radioactivity as well as for radiolabeled trimethylselenonium (TMSe). At lower doses of selenite (up to 500 micrograms/kg body wt), 30% of the administered dose was excreted. At higher doses of selenite, fractional urine excretion decreased as a function of the dose. The observed decrease in fractional urine excretion was not caused by changes in the absorption of the administered radiolabel. There was a direct relationship between the amount of the administered dose of selenite (up to 1500 micrograms/kg body wt) and the proportion of urinary [75Se] excreted as TMSe. Pretreatment with seleno compounds (10 or 100 micrograms Se/kg body wt as selenite, or selenomethionine) for 35 d before a challenge dose of [75Se]selenite did not influence the excretion of total [75Se] or of [75Se]TMSe in urine. Ingestion of a choline-deficient diet, which should deplete the availability of methyl groups, did not have any effect on excretion of total [75Se] or of [75Se]TMSe in urine after a challenge dose of [75Se]selenite (500 micrograms/kg body wt). The data presented here permit the following conclusions: 1) Production of TMSe is dose dependent, 2) production of TMSe from a single acute dose does not depend on the history of selenium intake and 3) rats fed a methyl-deficient diet are able to eliminate Se via formation of TMSe.     

Experimental selenium restriction in healthy adult humans: changes in selenium metabolism studied with stable-isotope methodology

Mechanisms responsible for selenium homeostasis were investigated in healthy adult men receiving diets adequate or low in Se (eight subjects per group). The appearance of a stable isotope of Se, 74Se, in plasma, urine, and feces was measured after oral administration of 74Se-selenite. One group received a restricted level of Se (18 +/- 1 micrograms/d) for 30 d, which resulted in a decrease in urinary, fecal, and plasma Se content compared with the group that consumed 119 +/- 1 micrograms/d. Low Se intake also resulted in decreased urinary 74Se excretion (27.2 +/- 1.4% vs 32.5 +/- 2.3% of the absorbed dose for the adequate intake), increased body retention of 74Se (74.8 +/- 3.1% vs 67.6 +/- 3.8% of the absorbed dose for the adequate group), and a contracted selenite-exchangeable metabolic pool (Se-EMP) (9782 micrograms for adequate Se and 6314 micrograms for the low-Se group; p less than or equal to 0.05). Measurement of Se-EMP may provide an additional and sensitive approach for assessing Se nutriture in human subjects.     

Dynamics of selenite metabolism in young men: studies with the stable isotope tracer method

Dynamics of selenite metabolism in young adult North American men were studied using an amino acid diet and the stable isotope tracer methodology during a short-term selenium replete-restriction phase. During the initial 10 days subjects consumed the diet providing a total daily selenium intake of 107.7 +/- 0.1 micrograms mostly as selenite. This was followed by selenium restriction at 11.4 +/- 0.1 micrograms/day (as impurities from diet components) for the next 34 days. Kinetic studies with the stable isotope tracer 74SeO32- were carried out on days 4 and 39 of the study. Kinetics of excretion of the tracer in feces and urine were followed from which body retention curves were constructed. The retention curves were resolved into two exponential decay components with half-lives of 2.4 +/- 0.3 and 162 +/- 9 days (mean +/- 1 SEM), respectively. Retention data and urine isotope enrichment curves were combined to determine dynamics of changes in the apparent body pool size for selenite (10.4 mg at t----infinity) as well as rates of turnover for this parameter.     

Long-term high copper intake: effects on copper absorption, retention, and homeostasis in men

BACKGROUND: Numerous studies have examined the effect of low and adequate intakes of copper on absorption and retention, but little information is available on the regulation of absorption and retention of copper when intake is high. OBJECTIVE: A study was conducted in men to determine the effect of long-term high copper intake on copper absorption, retention, and homeostasis. DESIGN: Nine men were confined to a metabolic research unit (MRU) for 18 d and were fed a 3-d rotating menu containing an average of 1.6 mg Cu/d. They continued the study under free-living conditions for 129 d, supplementing their usual diets with 7 mg Cu/d. They then returned to the MRU for 18 d and consumed the same diet as during the first period, except that copper intake was 7.8 mg/d. The stable isotope (63)Cu was fed to 3 subjects and infused into the other 6 on day 7 of each MRU period, and complete urine and stool collections were made throughout the study. Total copper and (63)Cu were determined by inductively coupled plasma mass spectrometry. Copper absorption, excretion, and retention were calculated on the basis of dietary, urinary, and fecal copper and (63)Cu. RESULTS: Results were as follows when comparing the high copper intake with the usual intake: fractional copper absorption was significantly lower, but the amount absorbed was significantly higher; excretion of the infused (63)Cu was significantly faster; and total retention was significantly higher. CONCLUSIONS: Homeostatic regulation of copper absorption and retention helped to minimize the amount of copper retained with high copper intake but was not sufficient to prevent retention of >0.6 mg Cu/d.     

Effect of chronic selenite supplementation on selenium excretion and organ accumulation in rats

We examined the effect of chronic selenite supplementation on whole body and selected organ selenium (Se) accumulation, urine excretion of total Se and trimethylselenonium ion, and Se balance in adult male rats. Animals were housed in metabolic cages and given either deionized water or water containing 4 micrograms of Se/mL as selenite for 30 d. Absorption of selenite was nearly complete, with only approximately 10% of ingested Se appearing in feces. There was a rapid rise in urinary Se that reached a plateau within a few days and accounted for 54 +/- 2% of the intake. Excretion of trimethylselenonium ion (TMSe) in urine increased rapidly, representing 35-40% of urinary Se in the supplemented animals compared with only 2% for the control group. In one experiment, rats were killed at 30 d and total carcass Se was measured using isotope dilution analysis. Supplemented rats had only a modest increase in whole body Se (94 +/- 4 micrograms Se vs. 66 +/- 3 in controls). Calculation of Se balance in the supplemented rats showed that approximately 35% of ingested Se could not be accounted for by urine plus fecal losses combined with the portion retained in the carcass. The results from this study demonstrate that under the condition of supplementation at 4 micrograms of Se/mL of drinking water, pathways other than urinary and fecal excretion may account for a substantial portion of Se loss.     

Effectiveness of selenium supplements in a low-selenium area of China

BACKGROUND: Selenium is an essential micronutrient with a recommended dietary allowance for adults of 55 mug/d. It functions as an essential constituent of selenoproteins. Although there is no evidence of selenium deficiency in the United States, people in many other areas of the world are selenium deficient, with the consequence that they are unable to express their selenoproteins fully. OBJECTIVE: We carried out a supplementation trial in a selenium-deficient population in China to assess the requirement for selenium as selenite and as selenomethionine. DESIGN: One hundred twenty subjects with an average selenium intake of 10 mug/d were randomly assigned and administered tablets containing no selenium or amounts as high as 66 mug Se/d for 20 wk. Plasma was sampled before supplementation and at 4-wk intervals during supplementation and was assayed for the 2 plasma selenoproteins, glutathione peroxidase and selenoprotein P. RESULTS: Full expression of glutathione peroxidase was achieved with 37 mug Se/d as selenomethionine and with 66 mug/d as selenite. Full expression of selenoprotein P was not achieved at the highest doses of either form. CONCLUSIONS: Full expression of selenoprotein P requires a greater selenium intake than does full expression of plasma glutathione peroxidase. This suggests that selenoprotein P is a better indicator of selenium nutritional status than is glutathione peroxidase and that the recommended dietary allowance of selenium, which was set with the use of glutathione peroxidase as the index of selenium status, should be revised. Selenium as selenomethionine had nearly twice the bioavailability of selenium as selenite.     

Absorption and retention of 75SeO3 in relation to soybean protein intake in the rat

The absorption and retention of ⁷⁵Se, given as an oral dose of ⁷⁵SeO₃, was studied in young male rats receiving different levels and sources of soy protein, with and without selenite and methionine supplementation. Rats fed a protein-free diet had a higher cumulative urine ⁷⁵Se excretion and a sligtly lower ⁷⁵Se absorption and ⁷⁵Se retention than rats fed diets containing 10% protein supplied as soya flour. Results indicated that supplementation with selenite decreased the fractional absorption and retention of selenium, but the overall effect was a marked increase in the total amount of selenium ingested, absorbed and retained. Methionine supplementation of a diet based on soya increased growth and PER: it also decreased slightly cumulative feces ⁷⁵Se excretion and increased ⁷⁵Se absorption, but only in rats fed diets supplemented with selenium. The present findings are consistent with the view that selenium homeostasis in the rat is maintained largely through changes in the urinary excretion of selenium and they show that an inadequate protein diet reduces the efficiency of retention of absorbed selenite.     

北方男性膳食钠摄入量及对钙需要量影响的研究

为研究北方男性膳食钠摄入量及其对尿钙排出量的影响 ,我们对健康男性 1 49人 (老年人 50名、青年人 48名、青少年 51名 )进行 5天称重法膳食调查 ,测定血清中钙、磷、肌、酐 ,2 4h尿中钙、磷、钠、肌酐。结果显示三组膳食钙的摄入量均低于我国供给量。2 4 h尿钠排出量 (即膳食钠摄入量 ) :青少年组 1 43.85mmol/d,青年组 2 53.7mmol/d,老年组 1 84.4mmol/d,三组间差异显著 ( P<0 .0 0 1 )。尿钙排出量与尿钠排出量呈显著正相关 ( P<0 .0 0 1 )。提示北方男性钙的需要量可能受钠的摄入量影响 ,在制定膳食钙供给量标准时应考虑钠的摄入量     

Effect of selenium on the connective tissue metabolism in rats]

Rats were chronically exposed to poisonous sodium selenite in concentrations 0.5 mg/kg b. m. for 10 weeks. As a result, hydroxyproline contents in blood serum increased, as well as its excretion with urine. It was proved that the procedure enhanced urinary glycosaminoglycane excretion and increased the contents of the protein-related glycosaminoglycanes in the serum. This was accompanied by increased quantities of keratane sulphate and heparin sulphate. The results confirmed that selenium poisonings influenced connective tissues.     

镁的不同摄入水平对生长期大鼠钙、磷、镁代谢及骨骼的影响

目的　研究饲料缺镁或高镁对生长期大鼠钙、磷、镁吸收代谢以及骨骼发育的影响。方法　 30只 SD大鼠 ,分为三组 ,每组 1 0只 ,单独喂养在有机玻璃代谢笼中 ,第一组大鼠饲喂缺镁饲料 (含镁 86mg/kg) ,第二组饲喂适量镁饲料 (含镁 548mg/kg) ,第三组为高镁饲料 (含镁540 2 mg/kg) ,三组饲料均为人工半合成制备 ,其中含钙 3.7g/kg,含磷 4g/kg。经过 2 5天对喂养方法及代谢笼的适应后 ,开始 5天期的代谢实验。每天记录大鼠的进食量 ,分别收集每个大鼠的粪、尿。代谢实验结束后 ,禁食 1 2 h,在乙醚麻醉下 ,心脏采血并处死大鼠 ,取股骨、胫骨测定重量、长度和体积后 ,与肾脏一起储存于 - 2 0℃ ,待测钙、镁和磷的含量。结果　缺镁和适量补镁对钙的表观吸收基本没有影响 (86% ) ,饲料中过量的镁使大鼠钙的表观吸收略有下降 (83% ) ,高镁使尿钙排出显著增加 ,降低了钙在体内的滞留 ;饲料高镁使磷的表观吸收显著下降。但尿磷排出减少 ,磷在体内滞留反而增加。随着饲料中镁含量的增加 ,粪和尿中镁的排泄均大幅度上升 ,可见镁的内环境稳定由肠道和肾脏共同调节。结论　低镁和高镁饲料均不利于生长期大鼠骨骼的生长发育。低镁饲料使大鼠肾钙、磷蓄积 ,可能是肾结石形成的主要原因。     

Plasma and urinary phyto-oestrogens as biomarkers of intake: validation by duplicate diet analysis

Estimating intake of phyto-oestrogens (PO) is difficult because there is inadequate information on the PO content of foods. Development of a biomarker of intake is therefore necessary for carrying out epidemiological studies. We aimed to validate a newly constructed PO database, containing more than 600 values assigned to foods by using duplicate diet analysis, and to investigate the relationships between measured PO intake, urinary excretion and plasma concentrations of PO. Fourteen subjects with estimated dietary intakes of PO ranging from 0 to 44 mg/d, measured by 7 d weighed intake, completed a duplicate diet collection over 24 h. Concurrently, a 24 h urine collection, validated using p-aminobenzoic acid, was obtained and one timed spot plasma sample taken. Duplicate diets, complete urine collections and plasma samples were analysed for total genistein and daidzein using liquid chromatography-MS to determine PO intake. The potential for 24 h urinary excretion and plasma PO concentrations to reflect dietary intake was investigated. Mean estimated and measured dietary PO intakes were 12.3 and 11.0 mg/d respectively. The correlation between estimated intake and measured intake of PO was highly significant (r 0.98, P<0.001). Urinary excretion (24 h) and plasma concentrations of PO were significantly related to measured dietary PO intake (r 0.97, P<0.001 and r 0.92, P<0.001 respectively). The relationship between 24 h urinary PO excretion and timed plasma concentrations was also significant (r 0.99, P<0.001). These findings validate the PO database and indicate that 24 h urinary excretion and timed plasma concentrations can be used as biomarkers of PO intake.     

Urinary excretion of purine derivatives as an index of microbial protein synthesis in the camel (Camelus dromedarius)

Five experiments were carried out to extend knowledge of purine metabolism in the camel (Camelus dromedarius) and to establish a model to enable microbial protein outflow from the forestomachs to be estimated from the urinary excretion of purine derivatives (PD; i.e. xanthine, hypoxanthine, uric acid, allantoin). In experiment 1, four camels were fasted for five consecutive days to enable endogenous PD excretion in urine to be determined. Total PD excretion decreased during the fasting period to 267 (SE 41.5) micromol/kg body weight (W)0.75 per d. Allantoin and xanthine + hypoxanthine were consistently 86 and 6.1 % of total urinary PD during this period but uric acid increased from 3.6 % to 7.4 %. Xanthine oxidase activity in tissues (experiment 2) was (micromol/min per g fresh tissue) 0.038 in liver and 0.005 in gut mucosa but was not detected in plasma. In experiment 3, the duodenal supply of yeast containing exogenous purines produced a linear increase in urinary PD excretion rate with the slope indicating that 0.63 was excreted in urine. After taking account of endogenous PD excretion, the relationship can be used to predict purine outflow from the rumen. From the latter prediction, and also the purine:protein ratio in bacteria determined in experiment 5, we predicted the net microbial outflow from the rumen. In experiment 4, with increasing food intake, the rate of PD excretion in the urine increased linearly by about 11.1 mmol PD/kg digestible organic matter intake (DOMI), equivalent to 95 g microbial protein/kg DOMI.     

Increase of urinary ketone body excretion in selenium-deficient rats is a ketone-specific change.

The effects of selenium (Se) deficiency on urinary ketone body excretion in starved rats were examined. Rats were fed a basal diet which was Se-deficient (Se content: 0.011 micrograms/g) or a Se-adequate diet (the basal diet supplemented with 0.1 micrograms Se/g as sodium selenite). On the 11th and 22nd week of the feeding period, Se-deficient status in rats fed the basal diet was verified by the observation that the Se content and glutathione peroxidase activity in their plasma, erythrocytes, and livers were markedly lowered. On the 4th, 6th, 11th, 15th, and 22nd week, the rats were starved for 48 h and the urinary excretion of ketone bodies (acetoacetate (AcAc) and 3-hydroxybutyrate (3-OHBA)), urea, and creatinine were examined. The urinary excretion of AcAc and 3-OHBA during the second 24 h of the 48-h starvation period were markedly higher in the Se-deficient rats than in the Se-adequate rats for all weeks examined, while the urine volume and the excretion of urea and creatinine were similar in the Se-deficient and Se-adequate rats, irrespective of the feeding period and the number of hours of starvation. On the 22nd week, the plasma ketone body levels were also determined and significantly higher plasma 3-OHBA levels were observed in the Se-deficient rats than in the Se-adequate rats 72 h after starvation began. These results indicate that Se deficiency causes an increase of urinary ketone body excretion in starved rats and that the increase is ketone-specific with no changes in major urinary profiles.     

Dietary carnitine intake and carnitine status in endurance-trained males

Background: Carnitine is an integral component of fatty acid transfer into the mitochondria, and also buffers excess intramitochondrial acyl‐CoA. It has previously been suggested that athletes may be at risk of low carnitine status and could therefore benefit from carnitine supplementation. Objective: To report the habitual dietary carnitine intakes of endurance‐trained adult males, and to determine whether they are at risk of carnitine insufficiency by measuring plasma and urinary carnitine concentrations. Methods: Fourteen non‐vegetarian endurance‐trained males completed a seven‐day weighed food record and exercise logs to determine habitual dietary carnitine intake. Resting venous blood samples and 24‐hour urine collections were used to determine plasma carnitine concentration and urinary carnitine excretion. Results: The mean dietary carnitine intake was 64 (range 21–110) mg/day. Mean ± SD resting plasma total carnitine was 44 ± 7 µmol/L and acyl : free carnitine ratio was 0.28 ± 0.11, which were within normal ranges. Urinary carnitine excretion was 437 ± 236 µmol/day. There was no correlation between dietary carnitine intake or dietary macro‐ and micronutrients and plasma carnitine or urinary carnitine excretion. Conclusion: The results of the present study indicate there is no evidence that endurance‐trained males consuming a mixed diet are at risk of carnitine insufficiency.     

Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites

Biochemical markers of niacin status were studied in healthy young men fed 6.1 to 32 niacin equivalents (NE) per day over an 11-wk period while residing in a metabolic unit. Methylated metabolites of niacin, N1-methylnicotinamide (NMN) and N1-methyl-2-pyridone-5-carboxamide (2-pyr), in urine and plasma were determined during periods of low (6.1 or 10.1 NE per day), adequate (19 NE per day = 1 RDA) and high (25 or 32 NE per day) niacin intakes and after small test doses of nicotinamide. Urine excretion of less than 1.2 mg/d of either NMN or 2-pyr was a reliable indicator of subjects receiving the lowest intake of 6.1 NE/d, but the NMN metabolite was a better marker of subjects ingesting 10.1 NE/d. The ratio of 2-pyr/NMN in urine was not as good a measure of the 6.1 NE/d intake as the individual metabolite excretions and was not responsive to the 10.1 NE/d intake. Plasma niacin metabolites were generally not as reliable as urinary metabolites for identifying subjects receiving low niacin intakes, however, values for plasma 2-pyr dropped quickly and were eventually nondetectable. After a 1 RDA oral dose of nicotinamide, increases in urine and plasma 2-pyr levels above pre-dose baseline values were significantly decreased in subjects receiving low, as compared to adequate, niacin intake. A leucine supplement had no effect on the rate of repletion of niacin-deficient subjects nor on the level of methylated niacin metabolites in urine or plasma.     

Investigations on the nutritional status of advanced breast cancer patients. The influence of long-term treatment with megestrol acetate or tamoxifen

The nutritional status of three groups of postmenopausal women (age 41-80 yrs) with advanced breast cancer was investigated with special reference to vitamin B6. The interference of hormonal treatment was studied with respect to the progestin megestrol acetate (Group MA, n = 14) and the antiestrogen tamoxifen (Group TAM, n = 15) compared with untreated patients (Group U, n = 11). Healthy postmenopausal women served as controls (Group C, n = 16). Nutritional status was judged from body mass index (BMI), vitamin and trace element status, hematology, and clinico-chemical parameters. Intake of nutrients was calculated from a food record. Hormonal status was studied by analysis of LH, FSH, and prolactin in plasma and of steroids and catecholamines and their metabolites in 24-hour urine. Compared with values for Group C, nutrient intake, hematology, clinico-chemical parameters, and 24-hour urinary excretion of catecholamines and their metabolites of patient groups (U, TAM, and MA) were not significantly different. The BMI of patients was significantly higher (by about 10%; 60% showed an overweight) than that of controls. With respect to fat-soluble vitamin status, significantly lower plasma levels of vitamin A (at least 40% lower, with deficient levels in more than 50% of the patients), D (40% lower), and E (20% lower) were found for Group U. However, water-soluble vitamin status of the four groups was fairly similar. A significantly higher excretion of xanthurenic acid in 24-hour urine, after an oral tryptophan load, was observed for Groups TAM and MA. This is most probably the result of hormonal treatment without affecting vitamin B6 status. Small, but significant, differences between groups were found for trace element status, especially with respect to lower plasma selenium of Group U (25% lower). LH, FSH, and prolactin in plasma and excretion of steroids in 24-hour urine showed levels that could be expected for controls and for untreated and hormonally treated patients. We concluded that the nutritional status of all patients is reasonably adequate. Hormonal treatment did not influence vitamin B6 status, although levels of vitamins A, D, and E and of selenium seem to be elevated.