Factors to take into account when interpreting 25-hydroxy-vitamin D serum levels.

BACKGROUND: Assessing vitamin D status, typically evaluated using serum or plasma 25-hydroxy vitamin D [25(OH)D] concentration, is complex because of various influencing factors. METHODS: Seasonality significantly affects intra-individual variability in 25(OH)D levels. This variation can be addressed by employing cosinor functions that are tailored to the geographical location of the patient to correct for seasonal effects. In addition to seasonality, genetic factors, such as DBP polymorphism and body composition, particularly adiposity, play crucial roles. Dialysis patients with DBP 2-2 phenotype exhibit higher vitamin D requirements. Genotyping/phenotyping of DBP allows for better tailored vitamin D supplementation. The lipid-soluble nature of vitamin D also interacts with plasma components such as serum triglycerides, which can influence vitamin D measurements. Adiposity, which is negatively correlated with vitamin D concentration, necessitates body mass-based mathematical adjustments for accurate vitamin D assessment in subjects with extreme BMI values. CONCLUSIONS: Accordingly, vitamin D replacement therapy must be personalized, taking into account factors such as body size and seasonal variations, to effectively reach the target serum 25(OH)D concentrations.

Vitamin D Deficiency: An Underestimated Factor in Sepsis?

Vitamin D is an important immune modulator that is linked to infection susceptibility. It has been suggested that vitamin D deficiency plays a role in sepsis and septic shock because vitamin-D-related pathways are associated with various immunological, endocrine, and endothelial functions. Previous research has yielded inconclusive results regarding the link between mortality and vitamin D deficiency in sepsis patients. In patients with sepsis and severe vitamin D deficiency, an adequate vitamin D concentration may reduce mortality. Randomized controlled trials to assess the influence of vitamin D supplementation on clinical outcomes in sepsis patients with vitamin D deficiency are uncommon. We will provide an overview of the current knowledge about the relationship between vitamin D and sepsis in this review, as well as consider the potential value of vitamin D supplementation in this situation.

Sense and nonsense concerning biotin interference in laboratory tests.

INTRODUCTION: Biotin supplementation (mainly OTC preparations) has gained popularity. There are concerns about biotin interference in immunoassays and potential misdiagnosis, especially since the discovery of high dose therapy in MS. This review summarizes the dangers of biotin usage and possible countermeasures. METHODS: Immunoassays design determines whether positive or negative analytical errors may occur. Techniques using biotinylated reagent and biotin binding proteins may generate errors. In sandwich immunoassays, biotin causes lowered results. Competitive immunoassays are more vulnerable: biotin usage causes false increased results. The interference is platform dependent. Parameters vary in their susceptibility: a combination of false positives and negatives mimicking a coherent profile is dangerous, e.g. combining falsely lowered TSH with falsely elevated FT4/FT3 mimicking hyperthyreosis. Other susceptible parameters are thyroglobulin, DHEA-S, estradiol, testosterone, ferritin, progesterone, Vitamin D, Vitamin B12, PSA, PTH, LH, FSH, Troponins I and T, Pro-BNP. Digoxin and PSA may also be affected. Tumor markers and ß-hCG are robust. Inserts of serological markers of HIV, hepatitis B and C warn for biotin interference. RESULTS: Manufacturers have made assays less vulnerable for biotin interference. In doubtful cases, it is helpful to determine testosterone in females and estrogen in males. Both are elevated if biotin interference is present. Biotin supplementation should be discontinued. However, this is impossible in MS patients needing biotin, as interrupting this medication is discouraged. CONCLUSIONS: Solutions to overcome this interference are: informing patients prior to analysis (avoiding peak biotin values when sampling), choice of appropriate immunoassays, and use of biotin removing steps prior to analysis.

Impact of food and drinks on urine production: A systematic review.

CONTEXT: The impact of food and drinks on body fluid metabolism is of direct clinical relevance but current evidence remains fragmented. AIM: Synthesise current evidence on the role of food and drinks in urine production. METHODS: Systematic review as per PRISMA guidelines using MEDLINE and EMBASE databases (completed October 2019). Studies reporting on the effect of food, food constituents, and drinks on urine production were included. Two authors performed an independent extraction of relevant articles using predetermined data sets and completed quality-of-study indicators. RESULTS: A total of 49 studies were included, of which 21 enroled human subjects, and 28 were clinically relevant animal studies (all of which utilised rodent models). The included studies were determined to be of variable quality. High dietary sodium, as well as wine, spirits, high-caffeine coffee, and caffeinated energy drinks, increased urine production in human studies. Decreased urine production was associated with low dietary sodium and consumption of milk, orange juice, and high-salt/high-sugar drinks. In animal models, a variety of fruits, vegetables, herbs, spices, and honey were associated with increased urine production. CONCLUSION: Current evidence suggests that although several types of food and drinks may impact body fluid metabolism, the quality of the data is variable. Urine production appears to be influenced by multiple factors including composition (ie, moisture, macronutrients, and electrolytes), metabolite load, and the presence of specific diuresis-promoting substances (eg, caffeine, alcohol) and other bioactive phytochemicals. Future research is needed to support current evidence and the physiologic mechanisms underlying these findings.

Probiotics in cystic fibrosis patients: A double blind crossover placebo controlled study: Pilot study from the ESPGHAN Working Group on Pancreas/CF.

BACKGROUND: A potential positive effect of probiotics in cystic fibrosis (CF) on fecal calprotectin (FCP), pulmonary exacerbations and weight has been described in small controlled trials. METHODS: A double-blind multicenter cross-over study (2 × 4 m) was performed looking at abdominal pain, nutritional status, pulmonary function, pulmonary exacerbation, FCP and lactulose/mannitol gut permeability test. Patients kept a diary with daily scoring of abdominal pain, stool frequency and consistency as well as treatment changes. RESULTS: 31 CF patients entered the study of which 25 finished it. At start patients aged 9.3yrs (6.9-12.2), had a median BMI z-score of -0.5 (-1.5-0.08), height z-score of -0.4 (-1.1-0.05) and FEV1% of 100% (87.2-106.6). Median FCP at start was 61 µg/g (17-108) and gut permeability 0.079 (0.051-0.122). No significant changes were observed in the clinical parameters (BMI, FEV1%, abdominal pain, exacerbations). Despite being frequently abnormal (17/28 (61%) >50 mg/kg), FCP did not change significantly with probiotics. The proportion of patients with normal permeability was 8% during placebo and 32% during probiotic treatment (p = 0.031). FCP correlated to BMI z-score (p = 0.043) and gut permeability to abdominal pain (p = 0.015). The microbiome revealed a high predominance of Actinobacteria and Proteobacteriae. Probiotic supplementation did not result in a shift at the phylum nor at phylogenetic level. CONCLUSION: Normalization of gut permeability was observed in 13% of patients during probiotic treatment. However, none of the previously described effects could be confirmed.

Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial.

Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily ß-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (P<0·001) and gastrocnemius (P=0·001) muscle. To conclude, the body creatine pool declined over a 3-month vegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.

Quantitative urine test strip reading for leukocyte esterase and hemoglobin peroxidase.

BACKGROUND: Recently, urine test strip readers have become available for automated test strip analysis. We explored the possibilities of the Sysmex UC-3500 automated urine chemistry analyzer based on complementary metal oxide semiconductor (CMOS) sensor technology with regard to accuracy of leukocyte esterase and hemoglobin peroxidase results. We studied the influence of possible confounders on these measurements. METHODS: Reflectance data of leukocyte esterase and hemoglobin peroxidase were measured using CMOS technology on the Sysmex UC-3500 automated urine chemistry analyzer. Analytical performance (imprecision, LOQ) as well as the correlation with white blood cell (WBC) and red blood cell (RBC) counts (Sysmex UF-5000) were studied. Furthermore, the influence of urinary dilution, haptoglobin, pH and ascorbic acid as confounders was determined. RESULTS: Within- and between-run imprecision (reflectance signal) ranged from 1.1% to 3.6% and 0.9% to 4.2% for peroxidase and 0.4% to 2.5% and 0.4% to 3.3% for leukocyte esterase. Good agreement was obtained between the UF-5000 for RBCs and peroxidase reflectance (r=0.843) and for WBCs and leukocyte esterase (r=0.821). Specific esterase activity decreased for WBC counts exceeding 100 cells/µL. Haptoglobin influenced the peroxidase activity, whereas leukocyte esterase and peroxidase activities showed a pH optimum between 5.0 and 6.5. A sigmoidal correlation was observed between urinary osmolality and peroxidase activity. CONCLUSIONS: CMOS technology allows to obtain high quality test strip results for assessing WBC and RBC in urine. Quantitative peroxidase and leukocyte esterase are complementary with flow cytometry and have an added value in urinalysis, which may form a basis for expert system development.

Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by ß-alanine transamination.

KEY POINTS: Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that ß-alanine is an efficient substrate for the mammalian transaminating enzymes 4-aminobutyrate-2-oxoglutarate transaminase and alanine-glyoxylate transaminase. The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of ß-alanine, which is in turn controlled by degradation of ß-alanine in liver and kidney. Chronic oral ß-alanine supplementation is a popular ergogenic strategy in sports because it can increase the intracellular carnosine concentration and subsequently improve the performance of high-intensity exercises. The present study can partly explain why the ß-alanine supplementation protocol is so inefficient, by demonstrating that exogenous ß-alanine can be effectively routed toward oxidation. ABSTRACT: The metabolic fate of orally ingested ß-alanine is largely unknown. Chronic ß-alanine supplementation is becoming increasingly popular for improving high-intensity exercise performance because it is the rate-limiting precursor of the dipeptide carnosine (ß-alanyl-l-histidine) in muscle. However, only a small fraction (3-6%) of the ingested ß-alanine is used for carnosine synthesis. Thus, the present study aimed to investigate the putative contribution of two ß-alanine transamination enzymes, namely 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T) and alanine-glyoxylate transaminase (AGXT2), to the homeostasis of carnosine and its methylated analogue anserine. We found that, when transfected into HEK293T cells, recombinant mouse and human GABA-T and AGXT2 are able to transaminate ß-alanine efficiently. The reaction catalysed by GABA-T is inhibited by vigabatrin, whereas both GABA-T and AGXT2 activity is inhibited by aminooxyacetic acid (AOA). Both GABA-T and AGXT2 are highly expressed in the mouse liver and kidney and the administration of the inhibitors effectively reduced their enzyme activity in liver (GABA-T for vigabatrin; GABA-T and AGXT2 for AOA). In vivo, injection of AOA in C57BL/6 mice placed on ß-alanine (0.1% w/v in drinking water) for 2 weeks lead to a 3-fold increase in circulating ß-alanine levels and to significantly higher levels of carnosine and anserine in skeletal muscle and heart. By contrast, specific inhibition of GABA-T by vigabatrin did not affect carnosine and anserine levels in either tissue. Collectively, these data demonstrate that homeostasis of carnosine and anserine in mammalian skeletal muscle and heart is controlled by circulating ß-alanine levels, which are suppressed by hepatic and renal ß-alanine transamination upon oral ß-alanine intake.

Folates from metabolically engineered rice: a long-term study in rats.

SCOPE: The biological impact of folates from folate rice, a metabolically engineered (biofortified) rice line, rich in folates, was investigated. Its consumption may be helpful to fight folate deficiency. Our objective was to investigate the potential of folate rice to supply the organism with folates and evaluate its biological effectiveness using a rat model. METHODS AND RESULTS: Five groups of 12 Wistar rats were monitored during a 7/12-wk depletion/repletion trial. Animals receiving folate-free diet (0 µg/rat/day) and those additionally receiving wild-type rice (on average 0.11 µg/rat/day) suffered from decreased hematocrit and lower folate concentrations in both plasma and RBCs. This resulted in serious morbidity and even lethality during the trial. In contrast, all animals receiving a daily supplement of folate rice or folic acid fortified rice (on average 3.00 µg/rat/day and 3.12 µg/rat/day, respectively) and those receiving a positive control diet (11.4 to 25.0 µg/rat/day), survived. In these groups, the hematocrit normalized, plasma and RBC folate concentrations increased and pronounced hyperhomocysteinemia was countered. CONCLUSION: Using an animal model, we demonstrated that biofortified folate rice is a valuable source of dietary folate, as evidenced by folate determination in plasma and RBCs, the alleviation of anemia and counteraction of pronounced hyperhomocysteinemia.

Agglutination of intravenously administered phosphatidylcholine-containing lipid emulsions with serum C-reactive protein.

BACKGROUND: C-reactive protein (CRP) is able to bind phospholipids in the presence of calcium. We wanted to investigate the reaction of CRP with various commercial fat emulsions and to explore the impact of CRP agglutination on serum CRP levels. MATERIALS AND METHODS: Serum specimens were mixed with Intralipid 20% (soybean oil-based fat emulsion), Structolipid (structured oil-based fat emulsion), Omegaven (fish oil-based fat emulsion), or SMOFlipid (mixed soybean oil-, olive oil-, and fish oil-based emulsion) in Tris-calcium buffer (pH 7.5). After 30 minutes of incubation at 37°C, CRP-phospholipid complexes were turbidimetrically quantified and flow cytometric analysis was performed. Similarly, CRP complexes were monitored in vivo, following administration of fat emulsion. RESULTS: CRP was able to agglutinate phospholipid-containing lipid droplets present in the soybean oil-based fat emulsion and the structured oil-based fat emulsion. To a lesser extent, agglutination was observed for fish oil-containing fat emulsions, whereas no agglutination was noticed for the mixed soybean oil-, olive oil-, and fish oil-based emulsion. Results for propofol-containing emulsions were comparable. Agglutination correlated with phospholipid content of the emulsions. When in vivo agglutination occurred, plasma CRP values dropped due to consumption of CRP by phospholipid-induced agglutination. CONCLUSIONS: In this in vitro experiment, we demonstrated agglutination of CRP with phospholipids in various fat emulsions. Research studies are required in patients to determine which effects occur with various intravenous fat emulsions.

Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans.

A polymorphism in the carnosine dipeptidase-1 gene (CNDP1), resulting in decreased plasma carnosinase activity, is associated with a reduced risk for diabetic nephropathy. Because carnosine, a natural scavenger/suppressor of ROS, advanced glycation end products, and reactive aldehydes, is readily degraded in blood by the highly active carnosinase enzyme, it has been postulated that low serum carnosinase activity might be advantageous to reduce diabetic complications. The aim of this study was to examine whether low carnosinase activity promotes circulating carnosine levels after carnosine supplementation in humans. Blood and urine were sampled in 25 healthy subjects after acute supplementation with 60 mg/kg body wt carnosine. Precooled EDTA-containing tubes were used for blood withdrawal, and plasma samples were immediately deproteinized and analyzed for carnosine and ß-alanine by HPLC. CNDP1 genotype, baseline plasma carnosinase activity, and protein content were assessed. Upon carnosine ingestion, 8 of the 25 subjects (responders) displayed a measurable increase in plasma carnosine up to 1 h after supplementation. Subjects with no measurable increment in plasma carnosine (nonresponders) had ∼2-fold higher plasma carnosinase protein content and ∼1.5-fold higher activity compared with responders. Urinary carnosine recovery was 2.6-fold higher in responders versus nonresponders and was negatively dependent on both the activity and protein content of the plasma carnosinase enzyme. In conclusion, low plasma carnosinase activity promotes the presence of circulating carnosine upon an oral challenge. These data may further clarify the link among CNDP1 genotype, carnosinase, and diabetic nephropathy.

Value and pitfalls in iodine fortification and supplementation in the 21st century.

Although the number of iodine-deficient countries has been reduced by almost 50 % over the last decade, it still remains a frequently misunderstood health problem. The most devastating effects of iodine deficiency occur during fetal development and childhood, periods in which sufficient iodine delivery remains critical. Besides the determination of thyroid size, the concentration of urinary iodine, serum thyroid-stimulating hormone and serum thyroglobulin are useful biomarkers to assess iodine status. Severe iodine deficiency is associated with neurological complications, cretinism, endemic goitre development, hypothyroidism, decreased fertility and increased infant mortality. The recommended iodine supplementation strategies are based on correction of iodine deficiency, close monitoring and evaluation of iodine administration, cooperation of the salt industry, training of local health care professionals and education of the population. Besides the multiple beneficial effects of supplementation, we present in this review a critical look at the possible side effects.

Determinants of ferritin and soluble transferrin receptors as iron status parameters in young adult women.

OBJECTIVE: To investigate associations between nutritional and non-nutritional variables and Fe status parameters, i.e. serum ferritin and soluble transferrin receptors (sTfR). DESIGN: Cross-sectional design. Fe status parameters were determined on a fasting venous blood sample. Nutritional variables were assessed using a 2 d food record and non-nutritional variables by a general questionnaire. A general linear model was used to investigate associations between the variables and Fe status parameters. SETTING: Region of Ghent, Dutch-speaking part of Belgium. SUBJECTS: Random sample of 788 women (aged 18-39 years). RESULTS: Median (interquartile range) ferritin and sTfR were 26.3 (15.9, 48.9) ng/ml and 1.11 (0.95, 1.30) mg/l, respectively. BMI and alcohol intake were positively associated and tea intake was negatively associated with serum ferritin. Women who used a non-hormonal intra-uterine device, who gave blood within the past year or who had been pregnant within the past year had lower serum ferritin values than their counterparts. Significant determinants of sTfR were smoking habit and pregnancy, with higher values for non-smokers and women who had been pregnant within the past year. CONCLUSIONS: The present study indicates that contraceptive use, time since last blood donation, time since last pregnancy, BMI, alcohol and tea intake are determinants of Fe stores, whereas smoking habit and time since last pregnancy are determinants of tissue Fe needs. When developing strategies to improve Fe status, special attention should be given to women who use a non-hormonal intra-uterine device, gave blood within the past year and had been pregnant within the past year.

Severe hyponatremia, hyperglycemia, and hyperlactatemia are associated with intraoperative hyperthermic intraperitoneal chemoperfusion with oxaliplatin.

BACKGROUND: Since the introduction of surgical debulking in combination with intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin in our institution, severe hyponatremia (sodium: 126.5 +/- 3.8 mmol/L), hyperglycemia (glucose: 22.37 +/- 4.89 mmol/L), and hyperlactatemia (lactate: 3.17 +/- 1.09 mmol/L) have been observed post HIPEC. This metabolic disorder was not observed in patients in whom cisplatin or mitomycin C was used as a chemotherapeutic drug. METHODS: In order to understand the pathophysiology of this finding, an analysis of our data was made. In a first analysis, plasma sodium was corrected for hyperglycemia based on the formula of Hillier. In a second analysis, the influence of total exchangeable sodium, total exchangeable potassium, and total body water on plasma sodium concentration was modeled. RESULTS: Analysis of our data revealed a double mechanism for the observed metabolic disorder: hyperglycemia caused by dextrose 5%, which is used as a carrier for the oxaliplatin, and major loss of sodium into the dialysate (256.7 +/- 68.7 mmol). CONCLUSION: Better control of hyperglycemia and intravenous compensation of sodium loss into the dialysate can attenuate the reported biochemical disturbance.

Guanidino compounds after creatine supplementation in renal failure patients and their relation to inflammatory status.

BACKGROUND: Specific guanidino compounds have been described as uraemic toxins and their concentrations are increased in renal failure due to dimished glomerular filtration, whereas the guanidino compound creatine is used as a performance-enhancing substance in athletes. The present study investigates the effects of creatine supplementation on plasma guanidino compounds in a chronic haemodialysis population. METHODS: Twenty male haemodialysis patients were included in a placebo-controlled cross-over trial. Patients were treated with creatine (2 g/day) or placebo during two treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma guanidino compounds and routine biochemical parameters were determined, as well as the prognostic inflammatory and nutritional index (PINI). RESULTS: Upon creatine supplementation, guanidinoacetate concentrations decreased by 15%, due to inhibition of creatine synthesis. Concentrations of alpha-keto-delta-guanidinovaleric acid increased three-fold and argininic acid concentrations doubled. Guanidinosuccinate concentrations did not change, but correlated inversely with CRP (r = -0.736; P = 0.001), PINI-score (r = -0.716; P = 0.002) and correlated positively with plasma urea concentration (r = 0.54; P = 0.02). CONCLUSIONS: Creatine supplementation in haemodialysis patients significantly altered the concentration of specific guanidino compounds. Guanidinosuccinate correlated positively with plasma urea and negatively with inflammation markers.

Epidemiological evidence for an association between habitual tea consumption and markers of chronic inflammation.

BACKGROUND: Tea consumption has been inversely related to the risk of cardiovascular disease, but the mechanism behind this cardioprotective role is not fully understood. In vitro and animal model studies suggest an anti-oxidative and/or anti-inflammatory role. We aimed at investigating the association between tea drinking and indicators of low-grade inflammation in humans. METHODS: We used observational data from 1031 healthy men participating in a larger cross-sectional study (BELSTRESS). Tea consumption was determined according to a semi-quantitative food frequency questionnaire. Blood samples were analysed for C-reactive protein (CRP), serum amyloid A (SAA), serum haptoglobin and plasma fibrinogen. RESULTS: Of all participants, 22% consumed tea regularly while 10% drank more than two cups per day. Tea drinkers were less obese, smoked less and drank less alcohol and coffee. CRP, SAA and haptoglobin were significantly associated with tea consumption, the effect being graded for SAA. Multivariate analysis did confirm the independence of the observed beneficial role of tea drinking. Fibrinogen levels were however not different between habitual tea consumers and non-consumers. Coffee drinking proved unrelated to chronic inflammation. CONCLUSION: Tea drinking might be of interest in reducing the inflammatory process underlying cardiovascular disease. In light of the fact that tea is the most consumed beverage in the world after water, our findings might be of importance from a public health perspective.

Creatine supplementation does not decrease total plasma homocysteine in chronic hemodialysis patients.

BACKGROUND: Hyperhomocysteinemia is present in the majority of chronic hemodialysis patients. Treatment with folic acid, vitamin B12, and vitamin B6 cannot fully normalize plasma homocysteine concentrations (tHcy). Previously we have demonstrated the tHcy-lowering effect of creatine supplementation in an animal model of uremia (Kidney Int 64:1331-1337, 2003). The present study investigates the effects of creatine supplementation on tHcy in a vitamin-repleted chronic hemodialysis population. METHODS: Forty-five hemodialysis patients receiving folic acid and vitamin B6 and B12 were included. Patients were treated with creatine (2 g/day) or placebo during 2 treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma tHcy, creatine, Kt/V(urea), folic acid, vitamin B12, and routine biochemistry were determined, as well as the prognostic inflammatory and nutritional index. RESULTS: All patients had elevated tHcy concentrations (21.2 +/- 5.6 micromol/L). Creatine treatment resulted in increased plasma and red blood cell creatine levels, documenting uptake of creatine. Creatine did not affect tHcy concentrations. There was no relationship between plasma creatine concentrations and tHcy concentrations. No changes in body weight, routine biochemistry, nutritional status, folic acid, or vitamin B12 were observed during the study. CONCLUSION: Creatine supplementation at a rate of 2 g/day does not further decrease tHcy concentrations in chronic dialysis patients already treated with high dose folic acid, vitamin B6, and B12 supplementation.

Creatine supplementation decreases homocysteine in an animal model of uremia.

BACKGROUND: Hyperhomocysteinemia is prevalent in more than 85% of patients with end-stage renal disease (ESRD) and is thought to contribute to the excess cardiovascular mortality and morbidity. Creatine is synthesized by methylation of guanidinoacetate with formation of S-adenosylhomocysteine and subsequently, homocysteine (Hcy). Creatine supplementation down-regulates its endogenous synthesis and, thus, may reduce Hcy production. The present study investigates the effect of creatine supplementation on Hcy concentrations in an animal model of uremia. METHODS: Male Wistar rats were either sham-operated and received a control diet (N = 8) or a 2% creatine-supplemented diet (N = 8), or underwent subtotal nephrectomy and received a control diet (N = 10) or a 2%-supplemented creatine diet (N = 10). After 2 weeks of treatment, total plasma Hcy, creatine, creatinine, folate, and vitamin B12 were determined, as well as hepatic folate and vitamin B12 concentrations. RESULTS: Plasma creatinine concentrations were higher in nephrectomized animals, but similar in creatine-supplemented and control diet-fed animals. Plasma Hcy was higher in nephrectomized animals but lower in creatine-supplemented nephrectomized animals compared to nephrectomized control diet-fed animals (12.1 +/- 2.4 micromol/L vs. 15.4 +/- 1.7 micromol/L; P < 0.01). Total plasma Hcy inversely correlated with plasma creatine concentrations (r =-0.39; P = 0.02). Plasma folate was higher in supplemented animals and hepatic tetrahydrofolate (THF) was higher in nephrectomized supplemented animals. Plasma vitamin B12 was similar in all groups, whereas hepatic vitamin B12 was higher in nephrectomized animals. CONCLUSION: Creatine supplementation can effectively lower plasma Hcy concentrations in an animal model of uremia and should be further investigated as a potential treatment for hyperhomocysteinemia in patients with ESRD.

The effect of supplementation with an antioxidant preparation on LDL-oxidation is determined by haptoglobin polymorphism.

The genetic polymorphism of haptoglobin (Hp) is an independent risk factor in the pathogenesis of atherosclerosis, a condition in which decreased resistance to in vitro oxidation of LDL-cholesterol is observed. We hypothesised that the Hp polymorphism is one of the factors modulating the resistance to Cu(2+)-induced oxidation of LDL during antioxidant supplementation. In this study, 74 middle-aged subjects with increased oxidative stress were allocated to either matched placebo or oral antioxidative treatment (Quatral) once daily for 16 weeks. Study parameters were increase of lag phase (DeltaLAG) and the ratio of lag phase during treatment period versus baseline (relative oxidation resistance, ROR), measured by Cu(2+)-induced oxidation of isolated LDL. Hp phenotypes were determined by starch gel electrophoresis. A significant and persistent increase of DeltaLAG (P < 0.05) and ROR (P < 0.01) were observed after 16 weeks of active treatment versus placebo. Interindividual differences in both parameters were significantly associated with the Hp polymorphism: in the active treatment group, DeltaLAG and ROR were significantly higher in Hp 1-1 subjects (P < 0.01) compared to Hp 2-1 and 2-2. Our data demonstrate that Hp phenotype is one of the modulating factors determining the increased resistance to Cu(2+)-induced oxidation of LDL during antioxidative treatment.