Fructose might be a clue to the origin of preeclampsia insights from nature and evolution

Takahiko Nakagawa, Andres-Hernando Ana Andres-Hernando, Tomoki Kosugi, Laura G. Sanchez-Lozada, Peter Stenvinkel, Karolina Kublickiene, S. Ananth Karumanchi, Duk Hee Kang, Hideto Kojima, Bernardo Rodriguez-Iturbe, Dean R. Tolan, Miguel A. Lanaspa, Richard J. Johnson

Research output: Contribution to journalShort surveypeer-review

2 Scopus citations


Preeclampsia is a hypertensive disorder of pregnancy and is due to abnormal placentation. The pathogenesis remains unclear. Fructose is biologically distinct from glucose and has a critical role in fetal growth in early pregnancy. Many species, including humans, produce fructose in their placenta during the first trimester to assist fetal growth and survival during a time when hypoxia is significant. Fructose is preferred over glucose in hypoxic tissues, and in the developing fetus, fructose has a critical role in stimulating the production of nucleic acids, lipids and glycosaminoglycans. Fructose production normally decreases significantly following the establishment of maternal-fetal circulation following placentation. However, if there is impaired placentation, local hypoxia will continue to drive fructose production. Excessive fructose metabolism drives endothelial dysfunction, oxidative stress, elevated blood pressure, insulin resistance, fatty liver, and a rise in uric acid and vasopressin levels, all of which are features of the preeclamptic state. In addition to fructose production, dietary fructose, for example, from soft drinks, would be additive and has been reported to be a strong independent risk factor for preeclampsia. Uric acid-associated endothelial dysfunction disturbs the invasion of the spiral artery, leading to placental ischemia and further placental hypoxia. Here, we summarize the previous literature regarding the physiological and pathological roles of fructose in pregnancy and propose studies to further investigate the pathogenesis of preeclampsia. [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)646-653
Number of pages8
JournalHypertension Research
Issue number3
StatePublished - Mar 2023

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to The Japanese Society of Hypertension.


  • Fructose
  • Hypoxia
  • Preeclampsia
  • Sugar
  • Uric acid
  • Vasopressin


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