Histamine is more commonly the result of high temperature spoilage than of long term, relatively low temperature spoilage. Nonetheless, there are a number of opportunities for histamine to form under more moderate conditions. Once the enzyme histidine decarboxylase has been formed, it can continue to produce histamine in the fish even if the bacteria are not active. The enzyme can be active at or near refrigeration temperatures. The enzyme is likely to be more stable than the bacteria in the frozen state and may be reactivated very rapidly after thawing.
Cooking can inactivate both the enzyme and the bacteria.
After cooking, recontamination of the fish with the enzyme-forming bacteria is necessary for additional histamine to form. For these reasons, histamine development is more likely in raw, unfrozen fish. The kinds of bacteria that are associated with histamine development are commonly present in the salt-water environment. They naturally exist on the gills and in the gut of live fish, with no harm to the fish. Upon death, the defense mechanisms of the fish no longer inhibit bacterial growth, and histamine-forming bacteria start to grow and produce histamine.