Pyrrolizidine alkaloids

Related Content
Changed on: 21.05.2021

Animal disease categories:

Profile

Description

Pyrrolizidine alkaloids (PA) are plant constituents that can damage health, especially the liver, after ingestion and are therefore undesirable in food and feed.

Occurrence

PAs have been identified in about 350 plant species worldwide. They are mostly found in the families of Asteraceae (daisy family), Boraginaceae (borage family) and Fabaceae (legume family). In Austria, native pyrrolizidine alkaloid-forming plants are, for example, members of the genus ragwort (synonym: ragwort; ragwort, common ragwort, grove ragwort), coltsfoot and butterbur from the composite family, viper's bugloss, borage and comfrey from the borage family.To date, more than 660 different PAs are known. The occurrence of PAs in plants varies greatly according to plant variety, climatic conditions, season and part of the plant.They can enter the food supply through the co-harvesting of pyrrolizidine alkaloid-containing plant parts and seeds (weeds) e.g. in spices, teas, leafy vegetables and lettuce. Animal foods such as honey, and less frequently milk or eggs, may also contain PAs if plants containing PAs are ingested via feed (EFSA 2015). Appropriate measures to avoid contamination of food with pyrrolizidine alkaloids include care in the cultivation and harvesting of lettuces, leafy vegetables and herbs, and of food before marketing.

Health risk

Animal studies showed that regular consumption of relatively small amounts of PA (chronic intake) can be carcinogenic. Regular intake of higher doses can also lead to irreversible liver damage (cirrhosis) and, in extreme cases, even death. For people who regularly consume tea (herbal tea, black tea, green tea, etc.), a health risk with regard to a possible carcinogenic effect cannot be excluded (EFSA 2017). Characteristic of poisoning are pain in the upper abdomen, abdominal dropsy, nausea and vomiting. Less frequently, jaundice and fever may occur. After a few weeks, liver enlargement and hardening is usually noticeable. Acute poisoning can be fatal. Because symptoms of poisoning may not appear until days later, the cause of the poisoning is rarely recognized.Acute cases of poisoning by pyrrolizidine alkaloids ingested in high doses have been described in humans. For example, in 1977/1978, two infants were affected who were given a particular species of ragwort (Senecio longilobus) as an herbal tea over the period of 4 to 14 days. For a two-month-old boy this ended fatally. A six-month-old girl was diagnosed with liver cirrhosis a few months later (BfR 2016a). Since the 1970s, poisonings have also been documented from India, Pakistan and Afghanistan. In Afghanistan, liver damage most recently occurred in 2008 in individuals who had eaten cereals contaminated with seeds containing PA for 2-6 months (BfR 2016a).

Situation in Austria

Since December 2020, on the basis of Regulation (EU) 2020/2040, maximum levels for pyrrolizidine alkaloids (PA) have been set in certain foods, such as tea, herbal tea, borage, some spices and food supplements. These will come into force on 1 July 2022. Herbal medicinal products may only be marketed in Austria if their use does not exceed a maximum daily dose of 1 µg PA (BASG 2016).

Studies on pyrrolizidine alkaloids (PA) in foodstuffs

In a study published by the European Food Safety Authority (EFSA) in 2015, pyrrolizidine alkaloid levels were analysed and evaluated in a total of 1,105 plant and animal products from six European countries (France, Germany, Greece, Italy, the Netherlands and Spain) (EFSA 2015).In Austria, we have been focusing on investigating PAs in tea, honey and spices since 2016.

Tea

Over 90 percent of all tea samples analysed on behalf of EFSA contained pyrrolizidine alkaloids (EFSA 2015). The mean concentration in tea infusions was 6 µg/l. The highest concentrations were found in Rooibos tea (up to 64 µg/l tea infusion).PA levels in tea, however, sometimes vary greatly. It often happens that a tested sample of a tea variety (e.g. green tea) of one brand does not contain any PA at all, while the same tea variety of another brand has very high levels.To map the situation in teas on the Austrian market, we have focused on 187 samples since 2016. PAs were detected in 54 percent of the tea samples. Of these, 15 samples were above the maximum level that will apply in the future. Compared to EU-wide investigations, teas from the Austrian market were on average contaminated with significantly lower pyrrolizidine alkaloid levels (0.8 µg/l tea infusion).

Spices and herbs

In certain herb and spice mixtures very high levels of PA were found. Dried spices such as oregano, marjoram or lovage are particularly often strongly affected. The contamination is presumably due to the co-processing of PA-forming foreign plants during harvesting. Although the consumption quantities of such herbs/spices are low in principle, they can make a considerable contribution to the total intake of PAs (BfR 2019, 2020). In 2019, we analysed 37 herb and spice samples for PAs. PAs were detected in 58 percent of the samples. In 6 samples the content was above the maximum level applicable in the future.

Food supplements

Food supplements (NEMs) containing pyrrolizidine alkaloid-forming plants sometimes have high levels of PAs, and 60 percent of the herbal food supplements tested in the EFSA study contained PAs at widely varying concentrations (EFSA 2015). The intake of such food supplements can significantly increase the intake of PAs compared to the intake via conventional food consumption and thus lead to significantly higher health risks, including in terms of acute poisoning.

Animal food

As part of the food chain, PAs can also enter animal foods such as milk, dairy products, eggs, meat and offal via contaminated feed. Currently, there is no evidence of PA concentrations in animal foods that would be of health concern to consumers. In the 2015 study published by EFSA, PA was found in only 2 percent of 746 samples of animal foods (milk, dairy products, eggs, meat, meat products). Eleven milk samples (6 percent) contained PA at low concentrations (between 0.05 and 0.17 µg/l). Only two egg samples contained traces of PA (0.10-0.12 µg/kg) and in other animal products no PA could be detected at all.

Honey

Similarly to tea, pyrrolizidine alkaloid contents also vary greatly in honey. Thus, it often happens that one type of honey contains no PA at all, while the other type of honey has very high contents. Due to their smaller body size, increased consumption of honey, especially in children, can lead to exposure to PAs that poses a health risk.To map the situation of honey on the Austrian market, we have examined 159 samples since 2016. PAs were detected in 62 percent of the honey samples.

Tips

The main sources through which consumers may ingest pyrrolizidine alkaloids (PAs) are teas contaminated with PAs (herbal, black, and green teas), dietary supplements, certain spices, and honey. These foods may contain amounts of PA that are of health concern to children and adults when ingested for prolonged periods of time. However, there is no acute health risk.

  • In principle, pay attention to a varied selection of foods. This can prevent one-sided exposure to potentially harmful substances.
  • Drinking water is best suited to cover the daily fluid requirement. Herbal tea and tea should only be consumed alternately with other drinks (drinking water, fruit tea, unsweetened diluted fruit juices).
  • Offer children primarily drinking water and not exclusively herbal tea as a thirst quencher. Fruit teas or unsweetened diluted fruit juices can also be offered as an alternative to herbal tea and tea. Black and green teas are generally not recommended for children due to the caffeine they contain.
  • Pregnant and breastfeeding women should not drink herbal teas regularly or to meet their fluid needs (including herbal nursing teas). Regular increased consumption of herbal teas should be discussed with your doctor.
  • Regularly changing the type or brand/manufacturer of tea and honey can reduce long-term consumption of highly contaminated products.
  • Honey is generally not suitable for infants in the first year of life. Since this can contain certain bacterial spores, which cannot be fought by the child's intestine yet (infant botulism).
  • Beware of food supplements containing PA-forming plants such as water astragalus, borage or comfrey. Consumption of such products is not recommended as they could immensely increase PA intake.
  • Beware of confusion with vegetables: When preparing lettuce, leafy vegetables and herbs, plant parts that cannot be assigned to any known edible plant should be discarded. Instead of dried products, use fresh, clearly identifiable herbs. Special care should be taken when wild herbs or plants are picked and processed by the consumer.

Professional information

Since 2011, the German Federal Institute for Risk Assessment (BfR) has regularly published opinions on PA levels in food and associated risks (BfR 2007, 2011, 2013, 2016a, 2020).

In June 2017, the European Food Safety Authority (EFSA) published a detailed risk assessment on PAs in food.


Regulation (EU) 2020/2040 amending Regulation (EC) 1881/2006 established the following maximum levels for pyrrolizidine alkaloids (PAs) in certain foods, which will enter into force on July 1, 2022:

"Product (1)Maximum level (*1) (μg/kg)
8.4. pyrrolizidine alkaloids
8.4.1. herbal infusions (dried product) (*2) (*3), except herbal infusions referred to in 8.4.2 and 8.4.4200
8.4.2. herbal infusions of rooibos, anise (Pimpinella anisum), lemon balm, chamomile, thyme, peppermint, lemon verbena (dried product) and mixtures consisting exclusively of these dried herbs (*2) (*3), except herbal infusions mentioned in 8.4.4400
8.4.3. tea (Camellia sinensis) and flavoured tea (*4) (Camellia sinensis) (dried product) (*3), excluding tea and flavoured tea mentioned under 8.4.4150
8.4.4 Tea (Camellia sinensis), flavoured tea (*4) (Camellia sinensis) and herbal teas for infants and young children (dried product)75
8.4.5. tea (Camellia sinensis), flavoured tea (*4) (Camellia sinensis) and herbal infant and young child teas (liquid product)1,0
8.4.6. food supplements containing herbal ingredients, including extracts (*2), other than the food supplements mentioned in 8.4.7.400
8.4.7. food supplements based on pollen (39)Pollen and pollen products500
8.4.8. borage leaves (fresh, frozen) placed on the market for the final consumer (*2) 750
8.4.9. dried herbs other than those mentioned in 8.4.10 (*2) 400
8.4.10. Borage, lovage, marjoram and oregano (dried) and mixtures consisting exclusively of these dried herbs (*2) 1000
8.4.11. Cumin (spice seeds)400

(*1) The maximum levels refer to the lower limit of the sum of the following 21 pyrrolizidine alkaloids:

  • Intermedin/lycopsamine, intermedin N-oxide/lycopsamine N-oxide,
  • senecionin/senecivernin, senecionin-N-oxide/senecivernin-N-oxide,
  • seneciphylline, seneciphylline-N-oxide,
  • retrorsine, retrorsine N-oxide,
  • echimidine, echimidine N-oxide,
  • lasiocarpine, lasiocarpine-N-oxide,
  • Senkirkin,
  • Europin, Europin-N-oxide,
  • heliotrin and heliotrin N-oxide.

As well as the following additional 14 pyrrolizidine alkaloids known to co-elute with one or more of the above 21 pyrrolizidine alkaloids, based on certain analytical methods currently in use:

  • Indicin, echinatin, bovin (possible coelution with lycopsamine/intermedin)
  • Indicin N-oxide, echinatin N-oxide, bovine N-oxide (possible co-elution with lycopsamine N-oxide/intermedin N-oxide)
  • Integerrimine (possible co-elution with senecivernin/senecionin)
  • Integerrimine N-oxide (possible co-elution with senecivernine N-oxide/senecionine N-oxide)
  • Heliosupin (possible co-elution with echimidine)
  • Heliosupin N-oxide (possible co-elution with echimidine N-oxide)
  • Spartioidin (possible co-elution with seneciphyllin)
  • spartioidin N-oxide (possible co-elution with seneciphyllin N-oxide)
  • Usaramine (possible co-elution with retrorsine)
  • Usaramine N-oxide (possible co-elution with retrorsine N-oxide)

Pyrrolizidine alkaloids which can be individually and separately identified by the analytical method used shall be quantified and included in the total.(*2) Notwithstanding stricter national rules in certain Member States on the placing on the market of plants containing pyrrolizidine alkaloids.(*3) The terms 'herbal infusions (dried product)' and 'tea (Camellia sinensis) (dried product)' refer to:

  • Herbal infusions (dried product) of flowers, leaves and herbs, roots and other parts of plants (in bags or loose)/Tea (Camellia sinensis) (dried product) of dried leaves, stems and flowers (in bags or loose) for the preparation of herbal infusions (liquid product)/Tea (liquid product)
  • Herbal tea/tea infusion powder. For tea extracts in powder form, a concentration factor of 4 shall be applied.

(*4) Flavoured tea means tea with flavourings and certain food ingredients with flavouring properties as defined in Regulation (EC) No 1334/2008 of the European Parliament and of the Council of 16 December 2008 on flavourings and certain food ingredients with flavouring properties for use in and on foods (OJ L 354, 31.12.2008, p. 34).For tea with fruits and other herbs, Article 2 of Regulation (EC) No 1881/2006 applies."

x