The effects of FRUctose restrIcTion on LivEr SteatosiS; the FRUITLESS study

Cardiovascular disease is a major threat to morbidity and mortality in Western
society. Evidence has accumulated that nonalcoholic fatty liver disease is an
independent risk factor for the development of cardiovascular disease. Fructose
plays an important role in the accumulation of fat in the liver as it serves as
a substrate for de novo lipogenesis and stimulates hepatic glucose disposal via
the disruption of the glucokinase-glucokinase regulatory protein complex.
Previous studies have already studied the lipogenic effect of fructose added to
standard diet. However, little attention has been paid to the effect of a diet
devoid of fructose. Therefore, this study aims to investigate the effects of
fructose restriction on hepatic fat accumulation and vascular risk. It is
hypothesized that fructose restriction will decrease hepatic fat content and
improve vascular status.

To quantify the change in hepatic fat (primary objective) and endothelial
function, arterial stiffness, plasma lipids, plasma biomarkers of inflammation
and endothelial function, and plasma advanced glycation end products (secondary
objectives) after six-weeks of fructose restriction.

For this, two groups will follow a six-week low fructose diet where the amount
of fructose restriction will be supplemented by either glucose powder
(intervention group) or fructose powder (control group) (with a minimum of 45
gram/day). Vitamin C will be supplemented in both groups to avoid deficiency.
At baseline and study closeout several cardiometabolic measurements will be
carried out, including magnetic resonance spectroscopy, laser doppler
flowmetry, reactive hyperemia peripheral arterial tonometry, carotid femoral
pulse wave velocity, blood withdrawal, and an oral glucose tolerance test.

A double-blind randomized placebo-controlled intervention study.

Low fructose diet, where the amount of fructose restriction will be
supplemented by either glucose powder (intervention group) or fructose powder
(control group) (with a minimum of 45 gram/day).

The proposed study diet will be similar to the diet of patients with hereditary
fructose intolerance, which will be closely monitored by an experienced
metabolic physician. This diet has been proven to be safe. Both glucose and
fructose powder are natural products that are well represented in the Western
diet. The only invasive test will be blood withdrawal (two times approximately
150 ml), which is associated with minimal health risk. Potential benefits are
an extensive screening for nonalcoholic fatty liver disease, cardiovascular
risk and type 2 diabetes mellitus, which are treatable entities.