Formation of malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) in fish and fish oil during dynamic gastrointestinal in vitro digestion

Food Funct. 2016 Feb;7(2):1176-87. doi: 10.1039/c5fo01401h.


Marine lipids contain a high proportion of polyunsaturated fatty acids (PUFA), including the characteristic long chain (LC) n-3 PUFA. Upon peroxidation these lipids generate reactive products, such as malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE), which can form covalent adducts with biomolecules and thus are regarded as genotoxic and cytotoxic. PUFA peroxidation can occur both before and after ingestion. The aim of this study was to determine what levels of MDA, HHE and HNE can evolve in the gastric and intestinal lumen after ingesting meals containing fish or fish oil using a dynamic gastrointestinal (GI) model (TIM). The impact of the fish muscle matrix, lipid content, fish species, and oven baking on GI oxidation was evaluated. MDA and HHE concentrations in gastric lumen increased for all meals during digestion, with the highest level found with herring mince; ∼ 25 μM MDA and ∼ 850 nM HHE. Aldehyde concentrations reached in intestinal lumen during digestion of fish containing meals were generally lower than in gastric lumen, while isolated herring oils (bulk and emulsified) generated higher MDA and HHE values in intestinal lumen compared to gastric lumen. Based on aldehyde levels in gastric lumen, meals containing herring lipids were ranked: raw herring (17% lipid) = baked herring (4% lipid) > raw herring (4% lipid) ≫ herring oil emulsion > herring oil. Herring developed higher concentrations of MDA and HHE during gastric digestion compared to salmon, which initially contained lower levels of oxidation products. Cooked salmon generated higher MDA concentrations during digestion than raw salmon. Low levels of HNE were observed during digestion of all test meals, in accordance with the low content of n-6 PUFA in fish lipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism*
  • Animals
  • Cooking
  • Digestion*
  • Fatty Acids, Unsaturated / metabolism
  • Fish Oils / analysis*
  • Gastrointestinal Tract / metabolism*
  • Humans
  • Lipid Peroxidation
  • Malondialdehyde / metabolism*
  • Models, Biological
  • Oxidation-Reduction
  • Salmon
  • Seafood / analysis*


  • Aldehydes
  • Fatty Acids, Unsaturated
  • Fish Oils
  • 4-hydroxy-2-hexenal
  • Malondialdehyde
  • 4-hydroxy-2-nonenal