Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study.

OBJECTIVE: The essential amino acid L-methionine is a potential compound in the prophylaxis of recurrent or relapsing urinary tract infection due to acidification of urine. As an intermediate of L-methionine metabolism, homocysteine is formed. The objective was to study the metabolism of L-methionine and homocysteine, and to assess whether there are differences between patients with chronic urinary tract infection and healthy control subjects. DESIGN: A randomized placebo-controlled double-blind intervention study with cross-over design. SETTING: Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany. SUBJECTS: Eight female patients with chronic urinary tract infection and 12 healthy women (controls). INTERVENTIONS: After a methionine-loading test, the volunteers received 500 mg L-methionine or a placebo three times daily for 4 weeks. MAIN OUTCOME MEASURES: Serum and urinary concentrations of methionine, homocysteine, cystathionine, cystine, serine, glycine and serum concentrations of vitamin B12, B6 and the state of folate. RESULTS: Homocysteine plasma concentrations increased from 9.4+/-2.7 micromol/l (patients) and 8.9+/-1.8 micromol/l (controls) in the placebo period to 11.2+/-4.1 micromol/l (P=0.031) and 11.0+/-2.3 micromol/l (P=0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6+/-22.0 micromol/l; P=0.003; n=20) and cystathionine (0.62+/-0.30 micromol/l; P=0.000; n=20) concentrations compared with the placebo period (33.0+/-12.0 and 0.30+/-0.10 micromol/l; n=20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake. CONCLUSIONS: Despite an adequate vitamin status, the supplementation of 1500 mg of L-methionine daily significantly increases homocysteine plasma concentrations by an average of 2.0 micromol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent such an increase.

High phosphorus intake only slightly affects serum minerals, urinary pyridinium crosslinks and renal function in young women.

OBJECTIVE: Assessment of the physiological effects of a diet rich in phosphorus in young women. DESIGN: Control period I--commercial basic diet containing 1700 mg P and 1500 mg Ca/day for 4 weeks. Supplementation period--a 6 week high-phosphorus period of 3008 mg P and 1995 mg Ca/day. Control period II--4 weeks washout with basic diet as in period I. SETTING: Institute of Nutritional Science, Friedrich Schiller University, Jena. SUBJECTS: Ten healthy women, aged 20-30y. INTERVENTIONS: Orange juice and tablets, containing supplements of Ca5(PO4)3OH and NaH2PO4, totalling 1436 mg elemental phosphorus per day. RESULTS: There was an increase of 10.7+/-13.7 pg/ml in serum PTH, a decrease of 0.6+/-0.6 ng/ml in serum osteocalcin, an increase of 73.6+/-136.6 nmol/mmol creatinine in urinary pyridinoline and of 19.3+/-36.0 nmol/ mmol creatinine in urinary deoxypyridinoline, and a decrease of 2.6+/-9.3 mg/l in urinary microalbumin. All changes were insignificant. There were no changes in serum levels of Ca, PO4 or Zn, in serum concentration of 1,25-(OH)2D3, and in urinary beta-2-microglobulin excretion. Phosphorus supplementation caused intestinal distress, soft stools or mild diarrhoea. CONCLUSIONS: In spite of a high phosphorus supplementation no significant changes in bone-related hormones, pyridinium crosslinks as markers of bone resorption and parameters of renal function in young women were found.

31P-magnetic resonance spectroscopy (31P-MRS) of human allografts after renal transplantation.

BACKGROUND: 31P-Magnetic resonance spectroscopy (31P-MRS) can be used as a non-invasive tool for measuring the relative intracellular concentrations of several phosphorus metabolites in different organs. Various pathological conditions are characterized by different metabolic patterns. We studied the value of 31P-MRS after renal transplantation with both an uneventful and a clinically complicated course. METHODS: We determined the relative concentrations of phosphate-containing metabolites in renal allografts of humans with 31P-MRS (1.5 Tesla) in the first few weeks after transplantation; 18 patients with an uneventful clinical course and 10 patients who required dialysis after transplantation were examined. Six patients with a stable allograft function 2-3 months after transplantation served as controls. RESULTS: In patients with primary allograft function, we found a significant correlation between the phosphomonoester/phosphodiester-ratio (PME/PDE) (r = 0.66, r < 0.01) and the time after transplantation, but no correlation between the nucleoside triphosphate (beta-NTP)-concentration (r = -0.11) and the time course. In the patients with primary or early allograft dysfunction caused by histologically proven rejection (n=5), we found a low beta-NTP compared to patients with an uncomplicated clinical course (0.09+/-0.01 vs 0.15+/-0.03), but no differences in the PME/PDE ratio (0.73+/-0.21 vs 0.80+/-0.21). In contrast, the PME/PDE ratio was lowered in three patients with delayed graft function caused by acute tubular necrosis (0.45+/-0.07 vs 0.80+/-0.21), but the beta-NTP concentration was not reduced (0.15+/-0.003 vs 0.15+/-0.03). The 31P-MR spectrum of two patients with cyclosporin A damage was not altered compared to the controls. CONCLUSIONS: 31P-MRS can be used in patients in the early period after renal transplantation. A significant correlation between the PME/PDE ratio and the time course but no change in the beta-NTP concentration was found in patients with primary allograft function in the first 4 weeks after renal transplantation. Different patterns of 31P-MR spectra were observed depending on the different causes of primary and early transplant dysfunction.

Vitamin status in patients with chronic renal failure.

Many factors complicate the effort for a recommendation on individual vitamin requirements in CRF. On the basis of our present incomplete knowledge about the handling of vitamins in uremia, suggestions for appropriate supplementation only of water-soluble vitamins are given. Patients with advanced CRF without dialysis treatment should receive daily supplements of vitamin B6 (5 mg), ascorbic acid (70-100 mg), and the normal recommended daily allowance of the other water-soluble vitamins in addition to the vitamin intake from the diet. We give folic acid only in patients taking antifolate drugs or in combination with iron in iron deficiency state and anemia (1 tablet of Folicombin contains 0.5 mg folic acid and 0.4 g elemental iron). There is still a pressing need for more data on the vitamin status, on vitamin requirements, and on long-term effects of vitamin administration in CRF.

[Vitamin A status of patients with chronic renal failure in relation to renal osteodystrophy]. / Untersuchungen über den Vitamin-A-Status von Patienten mit chronischer Niereninsuffizienz in Beziehung zur renalen Osteodystrophie.

In patients with chronic renal insufficiency and dialysis patients as well as in normal persons determinations of vitamin A in the serum and in the bone were performed and related to the parameters of the bone metabolism and to the histomorphometric investigation of the bone. The vitamin A serum levels were significantly increased in the two groups of patients, however, did not show any differences between the patients with an osteoidosis or the combination of osteoidosis and fibroosteoclasia. There were no correlations to calcium, phosphorus, PTH and to the alkaline phosphatase as well as to the individual histomorphometric data. The vitamin A content of the bone was low and did not show any differences to the normal persons. On the other hand, there were significant relations between the parathormone and the parameters of the regeneration and the absorption of the bones. An additional influence of vitamin A on the bone disturbance, eventually by the activation of the osteoclasts cannot be excluded.

Serum vitamin E levels in patients with chronic renal failure.

27 patients with chronic renal failure, 21 patients on chronic intermittent dialysis treatment and 27 healthy controls were tested for serum level of vitamin E estimated spectrophotometrically. Both patient groups had significant higher mean values (12.1 +/- 1.2 and 7.2 +/- 0.8 micrograms/ml respectively) in comparison with normal controls 4.6 +/- 0.7 micrograms/ml). No correlation was found to serum creatinine, hematologic values, protein and lipoprotein concentration, nor to mode and duration of treatment regimes. Vitamin E was not extracted from blood throughout dialysis. Under normal conditions of conservative or dialysis treatment of chronic renal failure patients vitamin E seems not to be a factor concerning uremic symptoms and there is no need for supplementation.