title: Fenofibrate causes elevation of betaine excretion but not excretion of other osmolytes by healthy adults.
abstract: BACKGROUND
  Cross-sectional data suggest that bezafibrate increases betaine excretion in dyslipidemic patients.
  
  
  OBJECTIVE
  We aimed to demonstrate that fenofibrate induces increased betaine excretion in normal subjects and explore whether other 1-carbon metabolites and osmolytes are similarly affected.
  
  
  METHODS
  Urine was collected from 26 healthy adults before and after treatment with fenofibrate (145 mg/day for 6 weeks). Excretions of betaine, N,N-dimethylglycine, free choline, myo-inositol, taurine, trimethylamine-N-oxide, carnitine, and acetylcarnitine were measured by liquid chromatography with mass spectrometric detection.
  
  
  RESULTS
  Fenofibrate increased the median betaine excretion from 7.5 to 25.8 mmol/mole creatinine (median increase 3-fold), P < .001. The median increase in N,N-dimethylglycine excretion was 2-fold (P < .001). Median choline excretion increased 12% (significant, P = .029). Participants with higher initial excretions tended to have larger increases (P < .001 in all 3 cases). Fenofibrate did not significantly change the median excretions of myo-inositol, taurine, trimethylamine-N-oxide, and carnitine. The excretion of acetylcarnitine decreased 4-fold on treatment, with no correlation between the baseline and after-treatment excretions. Changes in all urine components tested, except trimethylamine-N-oxide, positively correlated with changes in betaine excretion even when the median excretions before and after were not significantly different.
  
  
  CONCLUSIONS
  Fibrates increase betaine, and to a lesser extent N,N-dimethylglycine and choline, excretion. Other osmolytes are not elevated. Because the increase in betaine excretion depends on the baseline excretion, large increases in excretion in the metabolic syndrome and diabetes (where baseline excretions are high) could be expected. Replacement with betaine supplements may be considered.
authors.affiliation: Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand; Pathology Department, University of Otago Christchurch, Christchurch, New Zealand. Electronic address: michael.lever@otago.ac.nz.
authors.forename: Michael
authors.initials: M
authors.lastname: Lever
authors.affiliation: Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: McEntyre
authors.affiliation: Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand; Pathology Department, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Peter M
authors.initials: PM
authors.lastname: George
authors.affiliation: Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand; Pathology Department, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Sandy
authors.initials: S
authors.lastname: Slow
authors.affiliation: Pathology Department, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Chambers
authors.affiliation: ClinSciences, Dijon, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Foucher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001622:Betaine / Q000652:urine*; D002794:Choline / Q000652:urine; D002853:Chromatography, Liquid; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D012521:Sarcosine / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D000960:Hypolipidemic Agents; D001622:Betaine; C025138:dimethylglycine; D002794:Choline; D011345:Fenofibrate; D012521:Sarcosine
keywords: Betaine; Carnitine; Fenofibrate; Fibrate; Myo-inositol; One-carbon metabolism; Osmolyte; Trimethylamine-n-oxide