Fasting increases serum bilirubin levels in clinically normal, healthy males but not females: a retrospective study from phase I clinical trial participants

Griffin, Paul; Elliott, Suzanne; Manton, Kerry J.

doi:10.1136/jclinpath-2013-202155

Cited by 8 publications

(8 citation statements)

References 17 publications

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“…First, the study was not a placebo-controlled study. Therefore, it was not clear if the alteration in clinical and laboratory data was due to the administration of NMN or fasting for 5 h. In fact, the decrease in blood glucose level and the increase in serum bilirubin level were consistent with the findings frequently observed in healthy men after fasting [15]. Nonetheless, the dose-dependent increases in 2Py and 4Py levels in plasma samples supported the dosedependent uptake of NMN in the subjects.…”

Section: Discussionmentioning

confidence: 70%

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Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men

et al. 2020

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Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD +) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD + prevent these disorders in animal models. The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear. We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN. Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention. The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature. Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN. Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. Plasma concentrations of N-methyl-2-pyridone-5carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration. The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans.

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Section: Discussionmentioning

confidence: 70%

“…Whereas the plasma bilirubin levels increased, the glucose levels decreased significantly within the reference range. It is likely that these changes were due to fasting for 5 h [15]. All other parameters did not show any clinically significant changes at any single dose of NMN.…”

Section: Discussionmentioning

confidence: 84%

Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men

et al. 2020

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“…However, in a more recent study in rats estradiol was necessary to maintain amylase content in the pancreas [ 42 ], again suggesting species-specific hormonal influences. To the best of our knowledge, this is the first time that gender influences on serum activities of these enzymes have been documented in dogs, reconciling with known gender differences of several analytes in a number of species [ 43 , 44 ]. Such observations underline the need to account for sex as well as breed in assessing what is normal.…”

Section: Discussionmentioning

confidence: 94%

Serum Biochemical Phenotypes in the Domestic Dog

et al. 2016

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The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species.

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“…Physiological and preanalytical factors can impact laboratory values. For example Gender in case of hemoglobin and prolonged fasting, Gilbert's syndrome in case of bilirubin,[ 18 19 ] and therefore, must be considered to avoid unnecessary exclusions. Participants without any subclinical illness are defined as “Clinically normal,” at the same time, those participants whose laboratory values are outside the 95% confidence limit (as per the guideline) are called as “statistically normal.” Population specific RIs in trials could help reduce exclusions of “Clinically normal” participant on account of “Statistically abnormal” laboratory values.…”

Section: Discussionmentioning

confidence: 99%

Determination of reference intervals from a laboratory database of an academic clinical research unit in a tertiary care teaching hospital and an audit of out of range values

Figer

Raj

Thaker

et al. 2021

Perspectives in Clinical Research

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Background: Abnormal laboratory values are a common reason for the exclusion of participants in clinical studies, increasing the recruitment time and cost during conduct. The use of sample-specific reference intervals (RIs) may help to address this issue. Hence, the present study derived site-specific RIs using the department laboratory database and compare the proportion of “out of range” (OOR) values between the new and the old RIs used by the trial site. Methods: Institutional ethics committee approval was obtained. Data for hematology and biochemistry parameters were analyzed. Normality was assessed and RIs computed using nonparametric method. Data were partitioned for gender and descriptive statistics applied for demographics. The OOR values based on new RIs were compared with old RIs using Chi-squared tests. Between gender OOR proportions compared using Chi-squared test (significance at P < 0.05). Post hoc analysis was performed with Beasley's technique. Results: Data of 601 participants were analyzed. The median (Inter Quartile Range) age was 22 (47) years and 64.72% were male. New RIs for key parameters were: Haemoglobin (9.3–16.5 g/dl), alanine aminotransferase (11.4–47.74 U/I), aspartate aminotransferase (8.8–58 U/I), total bilirubin (0.27–1.4 mg/dl), and creatinine (0.59–1.36 mg/dl). Post partitioning, the RI for hemoglobin (g/dl) was lower (8.72–15.72) in females. The proportion of OOR values were lower with new RIs relative to old laboratory RIs ( P < 0.0001). Conclusion: A reduction in the proportion of OORs and a change in the upper and lower bound laboratory intervals with new RIs emphasize the need for sample-specific ranges to prevent unnecessary exclusions of volunteers from trials.

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Fasting increases serum bilirubin levels in clinically normal, healthy males but not females: a retrospective study from phase I clinical trial participants

Cited by 8 publications

References 17 publications

Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men

Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men

Serum Biochemical Phenotypes in the Domestic Dog

Determination of reference intervals from a laboratory database of an academic clinical research unit in a tertiary care teaching hospital and an audit of out of range values

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