Alkaloids in edible lupin seeds: A toxicological review and recommendations

Lupin seeds contain several bioactive substances with potential toxic effects in humans, especially quinolizidin alkaloids. The present report reviews the occurrence and toxicity of these alkaloids and estimates the risks from consumption of foods containing lupin seeds in the Nordic countries.
Lupin seeds have not until more recently been part of the human diet in the Nordic countries, but are now increasingly used, e.g. in bread and pasta, partially substituting wheat flour, and as snacks.
All lupin species studied contain quinolizidin alkaloids. Up to 500 lupin species occur worldwide, but only 12 in the Old World, and only seeds from few species have been used for human consumption (“edible lupins”), especially white lupin (Lupinus albus L.) and narrow-leaved lupin (Lupinus angustifolius L.).
Lupin varieties are often referred to as “bitter” when the total content of alkaloids is higher or equal to 10,000 mg/kg dry seeds and “sweet” when the content is lower or equal to 500 mg/kg dry seeds.
Traditionally, seeds from the edible lupin species contain high concentrations of bitter tasting and toxic quinolizidine alkaloids. Therefore, a debittering process, including cooking followed by soaking in water and daily replacement of water until bitterness disappears has been necessary before the seeds could be safely consumed. However, lupin seeds from cultivars low in alkaloids have been introduced in Europe for human consumption within the last decade.
In order to ensure safe use of lupin seeds in foods, the Advisory Committee on Novel Food and Processes in UK (ACNFP) concluded in 1996 that seeds from the low alkaloid lupin, the narrow-leaved lupin, are safe to use in the production of foods for human consumption provided that the level of lupin alkaloids in the seeds or derived lupin products does not exceed 200 mg/kg (and that the level of the mycotoxins phomopsins does not exceed 5 μg/kg). These recommended maximum levels for alkaloids and phomopsins were the same as the legal limits already operative in Australia. In 1998 France accepted the use of up to 10% of lupin flour made from a low alkaloid containing variety of white lupin called ARES as a food ingredient provided that the alkaloid content did not exceed 200 mg/kg.
Humans, especially children, are apparently much more sensitive to acute toxic effect from the alkaloids occurring in the “edible lupins” (the white and in the narrow-leaved lupins). Oral LD50-values for the alkaloids in rats range from 1700-2300 mg/kg bw. In comparison severe acute intoxications in humans have been reported at estimated intakes, which are two orders of magnitude lower.
Subacute/subchronic and feeding studies in animals have mainly shown reduced body weight, often with concomitant reduced food intake, but the studies are considered to be only of limited value for prediction of possible toxicity in humans caused by exposure to lupin seeds.
With respect to reproductive and developmental toxicity, there are only few studies available on the “edible lupin” seeds. There are some indication of effects, but the results are questionable due to the design of the studies. However, grazing on non-edible lupins (Lupinus taxiflorus, L. caudatus and L. nootkatensis) have been connected with developmental effect in domestic animals, where the teratogen is belived to be the quino-lizidin alkaloid anagyrine. It is noted that the North American lupin L. nootkatensis has been introduced in Iceland and now is widely spread in the country. Another lupin species, Lupinus consentinii has caused numerous cases of developmental effects in lambs. The suspected teratogen is multiflorine, which is structurally related to anagyrine.
It is not either clear whether the occasionally high amount of multiflorine in white lupins may be of concern.
Further, the apparently high sensitivity to acute intoxication, especially in children should be better studied.
Exposure to lupin alkaloids in the Nordic countries has been estimated based on highest recommended, as well as highest but still relevant levels of alkaloids, maximum use of lupin seeds in bread, pasta and snacks and high intakes of these three food categories. The estimated exposures are accordingly for children (weighing 20 kg) 0.6 – 1.4 mg/kg b.w. and for adults (weighing 60 kg) 0.3 – 0.8 mg/kg b.w.
For comparison case reports indicate that acute intoxications of adults caused by lupin alkaloids from “edible lupins” may occur after intake of 25-46 mg lupin alkaloids per body weight and case stories concerning small children indicate that intake of 11-25 mg/kg b.w. may be lethal.
In order to better ensure the safe use of lupin seeds in Nordic foods a series of recommendations are given concerning selection of proper lupin seeds for food use, analysis/exposure and toxicity data.