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Pyrrolizidine alkaloids

Pyrrolizidine alkaloids

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Description

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

Occurrence

Worldwide, PAs have been identified in about 350 plant species. They are frequently found within the families of the Asteraceae (daisy family), Boraginaceae (borage family) and Fabaceae (legume family). In Austria, native pyrrolizidine alkaloid-forming plants are, for example, representatives of the genus Greiskraut (synonym: ragwort; Jacob's ragwort, common ragwort, grove ragwort), coltsfoot and butterbur from the family of the composite plants, viper's bugloss, borage and comfrey from the family of the borage family.

To date, more than 660 different PAs are known. The occurrence of PAs in plants varies greatly by plant variety, climatic conditions, season, and part of the plant. They can enter the food supply by co-harvesting pyrrolizidine alkaloid-containing plant parts and seeds (weeds), e.g., in spices, teas, leafy vegetables, and lettuce. Animal foods such as honey, and less commonly milk or eggs, may also contain PAs if plants containing PAs are ingested through 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, death. There is a risk of health hazards especially for children, pregnant women and nursing mothers. 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.

In humans, acute cases of poisoning by pyrrolizidine alkaloids ingested in high doses have been described. For example, in 1977/1978, two infants were affected who were given a certain 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, based on Regulation (EU) 2020/2040, maximum levels have been set for pyrrolizidine alkaloids (PA) in certain foods, such as tea, herbal tea, borage, some spices and food supplements. These will come into effect on July 1, 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 food.

In a study published by the European Food Safety Authority (EFSA) in 2015, pyrrolizidine alkaloid levels were analyzed 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 PAs in tea, honey and spices since 2016.

Tea

More than 90 percent of all tea samples investigated 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). However, PA levels in tea sometimes vary widely. Thus, 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 shows 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

Very high levels of PA were found in certain herb and spice mixtures. 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 significant contribution to the total intake of PAs (BfR 2019, 2020). In 2019, we tested 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 that will apply 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 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 intake via conventional food consumption and thus lead to significantly higher health risks, including in terms of acute poisoning.

Animal food

PAs can also enter animal foods such as milk, dairy products, eggs, meat, and offal through the food chain 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 no PA at all could be detected in other animal products.

Honey

Similar to tea, pyrrolizidine alkaloid levels vary widely in honey. Thus, it often happens that one type of honey contains no PA at all, while another type of honey has very high levels. Due to their smaller body size, increased consumption of honey can lead to harmful levels of PA, especially in children. 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, if ingested over a long period of time, pose health concerns for children and adults. However, there is no acute health risk here.

  • 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 liquid requirement. Herbal tea and tea should only be consumed alternately with other beverages (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 because of 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 the 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. As it may contain certain bacterial spores that cannot yet be fought off by the infant's intestines (infant botulism)
  • Beware of dietary supplements containing PA-forming plants, such as water astragalus, borage, or comfrey. Consumption of such products is not recommended, as they could immensely increase the intake of PAs
  • Beware of confusion in vegetables: when preparing lettuce, leafy vegetables, and herbs, discard plant parts that cannot be assigned to any known edible plant. Instead of dried products, use fresh, clearly identifiable herbs. Special care should be taken when picking and processing wild herbs or plants yourself

Specialized 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.

In Regulation (EU) 2020/2040 amending Regulation (EC) 1881/2006, the following maximum levels for pyrrolizidine alkaloids (PAs) in certain foodstuffs were set, which will come into force on July 1, 2022:

Pyrrolizidine alkaloids Maximum level1 (μg/kg)
Herbal infusions (dried product)2, 3, except herbal infusions listed in 8.4.2 and 8.4.4. 200
Herbal teas of Rooibos, anise (Pimpinella anisum), lemon balm, chamomile, thyme, peppermint, lemon verbena (dried product) and mixtures consisting exclusively of these dried herbs2, 3 , except herbal teas mentioned in 8.4.4 400
Tea (Camellia sinensis) and flavored tea (*4) (Camellia sinensis) (dried product)3, except tea and flavored tea mentioned in 8.4.4. 150
Tea (Camellia sinensis), flavored tea 4 (Camellia sinensis) and herbal teas for infants and young children (dried product) 75
Tea (Camellia sinensis), flavored tea4 (Camellia sinensis) and herbal teas for infants and young children (liquid product) 1,0
Dietary supplements containing herbal ingredients, including extracts2, except those listed in 8.4.7. 400

Pollen-based dietary supplements (39); pollen and pollen products

500
Borage leaves (fresh, frozen) placed on the market for the final consumer2 750
Dried herbs, except dried herbs mentioned in 8.4.102 400
Borage, lovage, marjoram and oregano (dried) and mixtures consisting exclusively of these dried herbs2 1.000
Cumin (spice seeds) 400

 

1 Maximum levels refer to the lower limit of the sum of the following 21 pyrrolizidine alkaloids:

  • Intermedin/lycopsamine, intermedin N-oxide/lycopsamine N-oxide.
  • senecionine/senecivernine, senecionine N-oxide/senecivernine 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

and the following additional 14 pyrrolizidine alkaloids known to coelute with one or more of the above 21 pyrrolizidine alkaloids by certain analytical methods currently in use:

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

Pyrrolizidine alkaloids that can be identified individually and separately by the analytical method used shall be quantified and included in the total.

2 Notwithstanding stricter national regulations in certain Member States on the marketing of plants containing pyrrolizidine alkaloids.

3 The terms 'herbal infusions (dried product)' and 'tea (Camellia sinensis) (dried product)' refer to:

  • Herbal teas (dried product) made from flowers, leaves and herbs, roots and other plant parts (in bags or loose)/Tea (Camellia sinensis) (dried product) made from dried leaves, stems and flowers (in bags or loose) for the preparation of herbal teas (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 Flavored tea is tea with flavorings and certain food ingredients with flavoring properties as defined in Regulation (EC) No 1334/2008 of the European Parliament and of the Council of 16 December 2008 on flavorings and certain food ingredients with flavoring 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."

Last updated: 21.01.2022

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