Spielt eine erhöhte Fruktoseaufnahme und dadurch bedingte Hyperurikämie bei der Genese des metabolischen Syndroms eine Rolle?

Zusammenfassung

Neue Forschungsergebnisse aus den USA belegen einen möglichen Einfluss von erhöhtem Fruktoseverzehr auf die Entwicklung der Adipositas und der damit verbundenen Hypertonie sowie Dyslipidämie. In einer Übersicht werden daher die infrage kommenden Mechanismen der metabolischen Wirkung von Fruktose und Harnsäure bei der multifaktoriellen Genese des metabolischen Syndroms diskutiert. Hyperurikämie ist assoziiert mit Bluthochdruck und anderen Störungen des metabolischen Syndroms. Hoher Fruktoseverzehr kann nicht nur zur Hyperurikämie führen, sondern auch zu einer Hypertriglyzeridämie, wobei die endotheliale Dysfunktion als gemeinsamer biochemischer Mechanismus für diese Störungen des metabolischen Syndroms eine zentrale Bedeutung besitzt. Harnsäure hemmt die Bioverfügbarkeit von Stickstoffmonooxid (NO) im Gefäßendothel und kann durch die Freisetzung von proinflammatorischen Mediatoren Entzündungszellen aktivieren, wodurch das atherogene Risiko erhöht wird. Unterstützt wird die in tierexperimentellen Untersuchungen aufgestellte Hypothese zur Beteiligung von Harnsäure als unabhängiger Risikofaktor bei der Entstehung der primären Hypertonie auch durch klinische Studien über die Wirkung von harnsäuresenkenden Medikamenten. Große epidemiologische und klinische Studien zeigen insbesondere, dass auch eine asymptomatische Hyperurikämie (> 4 mg/dl) bei der Prognose der Gefäßkomplikationen berücksichtigt werden sollte. Weitere prospektive Interventionsstudien sind jedoch erforderlich, um zu entscheiden, ob Harnsäure als ein diagnostisches Kriterium in die Definition des metabolischen Syndroms mitaufgenommen werden sollte. Es besteht auch Forschungsbedarf, ab welcher Dosierung und unter welchen Begleitumständen Fruktose die Harnsäurespiegel und Lipidspiegel sowie die Bildung von Advanced Glycation Endproducts (AGEs) und modifizierten Lipoproteinen und den dadurch ausgelösten oxidativen Stress erhöht. Die Hinweise aus tierexperimentellen und klinischen Studien, dass durch erhöhte Harnsäurespiegel ausgelöste Endothelschäden beim Fetus zur Verminderung der Anzahl der Glomerula führen, und damit die Entstehung einer Hypertonie schon bei Kindern fördern könnte, bedürfen der weiteren Abklärung.

Abstract

New research findings from the USA confirm a possible effect of elevated fructose intake on the development of obesity and the related hypertension and dyslipidemia. The possible mechanisms of the metabolic impact of fructose and uric acid in the multifactorial genesis of metabolic syndrome are, therefore, discussed in an overview. Hyperuricemia is associated with high blood pressure and other disorders of metabolic syndrome. High fructose consumption can lead not only to hyperuricemia but also to hypertriglyceridemia. In this context, endothelial dysfunction takes on key importance as a common biochemical mechanism for these disorders of the metabolic syndrome. Uric acid inhibits the bioavailability of nitrogen oxide (NO) in the vascular endothelium. It can activate inflammatory cells by releasing pro-inflammatory mediators thereby increasing the atherogenic risk. The hypothesis advanced in animal experiments that uric acid is an independent risk factor in the onset of primary hypertension is backed by clinical studies on the impact of uric acid-reducing drugs. Comprehensive epidemiological studies and clinical trials show, more particularly, that asymptomatic hyperuricemia (> 4 mg/dl) should also be taken into account when predicting vascular complications. Further prospective intervention studies are, however, necessary in order to determine whether uric acid should be included as a diagnostic criterion in the definition of metabolic syndrome. There is also a need for research into from what dose onwards and under what accompanying circumstances fructose increases the uric acid and lipid levels and promotes the formation of advanced glycation end products (AGEs) and modified lipoproteins as well as the resulting oxidative stress. The indications from animal experiments and clinical trials that endothelial damage to the foetus caused by the elevated uric acid level can reduce the number of glomeruli and thus promote the onset of hypertension already in children, need to be examined further.

Schlüsselwörter

Harnsäure - Hyperurikämie - unabhängiger Risikofaktor - endotheliale Dysfunktion - Hypertension

Key words

uric acid - hyperuricemia - independent risk factor - endothelial dysfunction - hypertension

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