Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial.

BACKGROUND: There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease. OBJECTIVES: The aim of this study was to investigate the effects of fructose restriction on intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator. METHODS: Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index ≥ 60 consumed a 6-wk fructose-restricted diet (<7.5 g/meal and <10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHL content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center. RESULTS: Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: -57.0 g/d; 95% CI: -77.9, -39.5 g/d; and -38.8 µmol/d; 95% CI: -91.2, -10.7 µmol/d, respectively). Although IHL content decreased in both the intervention and control groups (P < 0.001 and P = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: -0.7% point, 95% CI: -2.0, -0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups. CONCLUSIONS: Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group.This trial was registered at clinicaltrials.gov as NCT03067428.

The 48-hour tetrahydrobiopterin loading test in patients with phenylketonuria: evaluation of protocol and influence of baseline phenylalanine concentration.

BACKGROUND: The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400 µmol/l is commonly used to test phenylketonuria patients for BH4 responsiveness. This study aimed to analyze differences between the 24- and 48-hour BLT and the necessity of the 400 µmol/l minimum baseline phenylalanine concentration. METHODS: Data on 186 phenylketonuria patients were collected. Patients were supplemented with phenylalanine if phenylalanine was <400 µmol/l. BH4 20mg/kg was administered at T = 0 and T = 24. Blood samples were taken at T=0, 8, 16, 24 and 48 h. Responsiveness was defined as ≥ 30% reduction in phenylalanine concentration at ≥ 1 time point. RESULTS: Eighty-six (46.2%) patients were responsive. Among responders 84% showed a ≥ 30% response at T = 48. Fifty-three percent had their maximal decrease at T = 48. Fourteen patients had ≥ 30% phenylalanine decrease not before T = 48. A ≥ 30% decrease was also seen in patients with phenylalanine concentrations <400 µmol/l. CONCLUSION: In the 48-hour BLT, T = 48 seems more informative than T = 24. Sampling at T = 32, and T = 40 may have additional value. BH4 responsiveness can also be predicted with baseline blood phenylalanine <400 µmol/l, when the BLT is positive. Therefore, if these results are confirmed by data on long-term BH4 responsiveness, we advise to first perform a BLT without phenylalanine loading and re-test at higher phenylalanine concentrations when no response is seen. Most likely, the 48-hour BLT is a good indicator for BH4 responsiveness, but comparison with long term responsiveness is necessary.

The effects of the calcium-restricted diet of urolithiasis patients with absorptive hypercalciuria type II on risk factors for kidney stones and osteopenia.

The calcium (Ca)-restricted diet of urolithiasis patients with absorptive hypercalciuria type II may decrease Ca excretion but increase biochemical markers of risk for osteopenia. We randomly allocated 25 patients from six hospitals into an experimental group (Ca restriction to 500 mg/day, oxalate-rich products discouraged and normalization of animal protein and sodium) and a control group (no restrictions) for one month. The urinary Ca excretion did not decrease significantly, but the oxalate excretion decreased, although not significantly. The hydroxyproline:creatinine ratio in fasting urine seemed to increase and the calcium:creatinine ratio to decrease. The deoxypyridinoline:creatinine ratio in fasting urine did not change. We conclude that our Ca-restricted diet, which is lower in Ca, animal protein and table salt due to the omission of dairy products, may be of benefit for absorptive hypercalciuria type II patients without enhancing the risk for osteopenia. However, a long-term clinical trial is required.

Plasma deoxycholic acid is related to deoxycholic acid in faecal water.

Bile acids are considered as a risk factor for colorectal carcinogenesis. They were analysed in samples of faecal water and plasma of fasting heparine blood from 23 urolithiasis patients. Linear regression showed that the highest percentage of variance (52%) was explained by the model: plasma deoxycholic acid (micromol/l) = -3.11 + 0.96(+/-0.25*) 10log deoxycholic acid in faecal water (micromol/l) + 0.35(+/-0.15*) pH of faecal water -0.41(+/-0.19#) defacation frequency (number of stools/day); *P < 0.05, #P = 0.055. In future studies, analysing blood levels of unconjugated deoxycholic acid may substitute faecal measurements.