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the presence of pyrrolizidine alkaloids in several of our favorite herbs

 
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Welcome, doctor!

A question that's been on my mind lately is the presence of pyrrolizidine alkaloids in several of our favorite herbs: Eupatorium, Tussilago, and Symphytum.

We know that some PA's are toxic, but not all; we know(?) that some of the toxic ones are in Eupatoreum perfoliatum. We also know that people have been using these plants as medicine for at least centuries. How do you balance your use of these plants with the risks associated with toxic alkaloids? Is there a safe level of consumption, such that one could use them short-term without long-term buildup in the liver?

Thanks for offering to do this Q & A and for all of your previous work!
 
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The Scoop on Pyrrolizidine Alkaloids…

Everyone has heard about Comfrey and the concern about the pyrrolizidine alkaloids in Comfrey causing hepato veno-occlusive disease (HVOD). The liver changes the pyrrolizidines into potent alkylating agents that react rapidly with cell constituents resulting in cellular destruction or abnormal cell growth patterns. Accumulation of this cellular damage is known as hepato veno-occlusive disease or HVOD. Research needs to be completed with comfrey and the prevelence of HVOD. Some of the cases that exist are sketchy but are reason for us to act cautiously. What most people don’t seem to realize is there are other medicinal herbs that also contain toxic pyrrolizidine alkaloids. The FDA has made it illegal to sell any of them for internal consumption. These herbs are Alkanna tinctoria (Alkanet), Anchusa officinalis (bugloss), Borago officinalis (borage), Crotalaria spp., Cynoglossum spp., Erechtites heiraciifolia, Eupatorium cannabium (hemp agrimony), Eupatorium purpureum (gravel root), Heliotropium spp., Lithospermum officinale (European gromwell), Packera candidissima, Petasites spp., (e.g., butterbur), Pulmonaria spp., (e.g. lungwort), Senecio jacobea (European ragwort), Senecio vulgaris (groundsel herb), Symphytum spp., (comfrey), and Tussilago farfara (coltsfoot).  (Eupatorium perforatum (Boneset) will probably be added to this FDA list soon.)

Some growers grow pyrrolizidine low or free Comfrey. Some manufacturers provide low or free pyrrolizidine Comfrey products. Some species of comfrey are known to contain more pyrrolizidine alkaloids than others. Symphytum officinalis is known to contain less than Symphytum uplandicum. However, Symphytum uplandicum has been sold as Symphytum officinalis in the past and the purchasers have not been aware they were buying the incorrect species. The  Comfrey leaves contain less alkaloid than the root generally and plants that do not go through the full winter season are thought to contain more of the alkaloid than comfrey that that lives in regions with a winter.

Comfrey has been used widely in the past. Animals have been fed comfrey to improve their health and to increase their productivity. Chickens fed comfrey have been known to lay more eggs while comfrey fed cows gave more milk. Although, many of us assume that Comfrey must be safe since it has been fed to animals without causing ill effects, the issue is that many people do not know why a farm animal dies and generally they simply bury a dead farm animal rather than dissecting it. Generally it will take days or more likely weeks for the chronic use of a plant with pyrrolizidine alkaloids to harm and kill an animal. That makes it hard to make the connection between the food and the death.

It appears that the pyrrolizidine alkaloids are bioactivated by phase I of the detox system. Although phase I (cytochrome P-450 system) is supposed to make toxins easier to excrete from the body. However, sometimes phase I makes them more toxic and if Phase II is not working up to par (These are all the conjugation actions) while Phase I is working hard, you will get a back up of pyrrolizidines and will be more likely to have HVOD. In research it appears that glutahtione conjugation specifically is very important as part of phase II for removing pyrrolizadines. So, taking glutathione as a supplement or using N-acetyl cysteine or alpha lipoic acid, vitamin C, Milk thistile, Turmeric or other methods to enhance glutathione could be helpful. Support of glutathione conjugation in addition to simply adding glutathione could also be helpful.

More understanding about pyrrolizidine alkaloids is needed regarding how the body processes them, and how the various herbs that have pyrrolizidines in them each effect humans.   Each herb has many other constituents in them and therefore will effect us differently.

Although Comfrey is the most common pyrrolizidine alkaloid containing herb used, there are additional herbs that contain pyrrolizidine alkaloids. They each are different in their effects.

Some people continue to use these herbs, while others have decided to use some, but only externally and other herbalists have simply decided not to use them at all. There are varied opinions about how to use them or to use them at all.


The American Herbal Products Association made the following statement in 1996 for pyrrolizidine alkaloids

AHPA recommends that all products with botanical ingredients which contain toxic pyrrolizidine alkaloids bear the following cautionary statement on the label:

For external use only. Do not apply to broken or abraded skin. Do not use when nursing.

Including but not limited to:

Alkanna tinctoria (alkanet), Anchusa officinalis (bugloss), Borago officinalis* (borage), Crotalaria spp., Cynoglossum spp., Erechtites hieraciifolia, Eupatorium cannabinum (hemp agrimony), Eupatorium purpureum (Joe Pye), Heliotropium spp., Lithospermum officinale (European gromwell), Packera candidissima, Petasites spp. (e.g., Butterbur), Pulmonaria spp. (e.g., lungwort), Senecio jacobaea (European ragwort), Senecio vulgaris (groundsel herb), Symphytum spp. (comfrey), and Tussilago farfara (coltsfoot).

* Borage seed oil is specifically exempt from the above label recommendation.

AHPA has been informed that there are comfrey cultivars that are very low in or devoid of PA content, and that there are processing technologies that allow removal of PAs from comfrey. Because AHPA‚s trade recommendation is based on PA content, it would not apply to „PA-free‰ product. AHPA expects of its members that they be able to substantiate and fully document any such safety claims via an appropriate laboratory testing program.

In reality there is a lot that can be said about pyrolizidine alkaloids and there is much conflictive data available in reports and research.  Check out the following links for some additional data:

http://medherb.com/Materia_Medica/Symphytum_-_Hepatotoxicity_of_pyrrolizidine_alkaloids_.htm

http://eclecticschoolofherbalmedicine.com/wp-content/uploads/2016/07/Pyrrolizidine-alkaloids-in-human-diet.pdf

list of additional pyrrolizidine links: http://eclecticschoolofherbalmedicine.com/comfrey-and-liver-damage/
 
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