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Herb Safety · natural doesn't mean safe
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In one pass Natural and safe have never been the same thing.
Educational content, not medical advice — consult a clinician.
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Chapter 1
Why natural doesn't mean safe
Natural and safe have never been the same thing.
This story is not saying herbs do not work. Quite the opposite. Artemisinin comes from sweet wormwood, and it won Tu Youyou the 2015 Nobel Prize in Physiology or Medicine; aspirin started out as willow bark; digoxin comes from foxglove. There is real medicine in herbs.
But precisely because they do real pharmacology, they can also do real toxicology. A molecule that can change something inside you can change the wrong thing. Where there is a drug effect, there is a toxic effect: that holds for pharmaceuticals, and it holds word for word for herbs. An herb in the body is acting as a drug, and none of the three layers of dose, purity and regulation becomes safe just because it is a plant.
One thing to remember first: while taking any herb, if your skin or the whites of your eyes turn yellow, your urine turns as dark as strong tea, or you have persistent tiredness, nausea or pain in the upper right abdomen, stop the herb and see a doctor right away to have your liver function checked (the chapter How to use herbs more safely covers this).
This story is not saying herbs do not work. Quite the opposite. Artemisinin comes from sweet wormwood, and it won Tu Youyou the 2015 Nobel Prize in Physiology or Medicine; aspirin started out as willow bark; digoxin comes from foxglove. There is real medicine in herbs.
But precisely because they do real pharmacology, they can also do real toxicology. A molecule that can change something inside you can change the wrong thing. Where there is a drug effect, there is a toxic effect: that holds for pharmaceuticals, and it holds word for word for herbs. An herb in the body is acting as a drug, and none of the three layers of dose, purity and regulation becomes safe just because it is a plant.
One thing to remember first: while taking any herb, if your skin or the whites of your eyes turn yellow, your urine turns as dark as strong tea, or you have persistent tiredness, nausea or pain in the upper right abdomen, stop the herb and see a doctor right away to have your liver function checked (the chapter How to use herbs more safely covers this).
Evidence · How much statin hides in red yeast rice
A tablet says 500 mg because someone measured it. An herb is a mixture of dozens to hundreds of compounds, and their amounts drift with where it was grown, when it was harvested and how it was processed.This is not an abstract worry. Researchers bought 28 red yeast rice products and tested them: at one day's labeled dose, the monacolin K inside ranged from 0.09 mg all the way to 10.94 mg (Cohen 2017). Incidentally, monacolin K has exactly the chemical structure of lovastatin, a prescription cholesterol drug. Eating red yeast rice means taking a statin; you just do not know how much (EFSA 2018).
Safety · What purity checks and regulation cover
You think you bought a pure plant. But herbal products have been found to contain heavy metals, and also pharmaceutical drugs that were not on the label (Ernst 2002). One honest note: how common this is, the data cannot say. Most of it is scattered reports, not rigorous epidemiology.China does have adverse-reaction monitoring for Chinese medicine. A national voluntary reporting system was set up in 1989, and about 10–15% of the reports it receives involve Chinese medicines, mostly ready-made formulated products (Zhang 2012). But regulation watches the product. You taking it long-term on your own, combining it with prescription drugs, not telling your doctor: all of that falls outside its view.
If it is a drug, treat it like one.
Chapter 2
How aristolochic acid causes cancer
One class of herbs leaves a fingerprint on your DNA. Decades later, doctors can still recognize it in a tumor.
These herbs contain aristolochic acid and come from the Aristolochia family: Guan Mu Tong, Guang Fang Ji and Qing Mu Xiang are among them. In 2012 the International Agency for Research on Cancer (IARC) classified both aristolochic acid and the plants that contain it as Group 1 carcinogens, the same group as aflatoxin and tobacco (IARC 2012). Group 1 means sufficient evidence that it causes cancer in humans; it describes how certain the evidence is, not how large the risk is.
In the body it is activated by metabolism and sticks to adenine (A) in DNA, forming an adduct (a chemical fragment stuck onto the DNA). When the DNA is copied, that A is read as a T. This A:T→T:A swap is something other carcinogens hardly ever leave behind. In upper urinary tract tumors from 19 patients with documented exposure, 72% of the mutations were of this kind (Hoang 2013).
It targets the kidney because kidney tubule cells actively pull it in from the blood. Its link to liver cancer is, for now, only a strong association; causation is not settled.
These herbs contain aristolochic acid and come from the Aristolochia family: Guan Mu Tong, Guang Fang Ji and Qing Mu Xiang are among them. In 2012 the International Agency for Research on Cancer (IARC) classified both aristolochic acid and the plants that contain it as Group 1 carcinogens, the same group as aflatoxin and tobacco (IARC 2012). Group 1 means sufficient evidence that it causes cancer in humans; it describes how certain the evidence is, not how large the risk is.
In the body it is activated by metabolism and sticks to adenine (A) in DNA, forming an adduct (a chemical fragment stuck onto the DNA). When the DNA is copied, that A is read as a T. This A:T→T:A swap is something other carcinogens hardly ever leave behind. In upper urinary tract tumors from 19 patients with documented exposure, 72% of the mutations were of this kind (Hoang 2013).
It targets the kidney because kidney tubule cells actively pull it in from the blood. Its link to liver cancer is, for now, only a strong association; causation is not settled.
Evidence · Kidney is causal, liver is association
Why the kidney in particular? The cells lining the kidney's proximal tubule carry a set of transporters (OAT1 and OAT3) that pull molecules like this out of the blood and into the cell. The more they pull in, the more piles up (Han 2019). The adducts can stay in the kidney for decades.Kidney and upper urinary tract: the causal case is solid.
The Belgian patients had preventive surgery: of 39 people, 18 (46%) already had upper urinary tract urothelial carcinoma, and every tissue sample tested contained aristolochic acid-related DNA adducts (Nortier 2000).Taiwan has the highest rate of upper urinary tract urothelial carcinoma reported anywhere. A molecular epidemiology study of 151 patients found that among those carrying A:T→T:A mutations, 83% had aristolochic acid DNA adducts in the renal cortex. Its conclusion is direct: aristolochic acid exposure contributes significantly to upper urinary tract urothelial carcinoma in Taiwan (Chen 2012).
Liver cancer: here we have to be honest.
One study sequenced the exomes (the protein-coding part of the genes) of 98 hepatocellular carcinomas (HCC) from Taiwan; 78% carried the aristolochic acid mutational signature. Widening to 1400 liver cancers from many regions, the figure for mainland China was 47% (Ng 2017). That number is striking.But a signature means exposure happened, not that it was the culprit. One review argues that aristolochic acid's target organ may depend on age: young animals develop liver tumors, whereas adults exposed to it mainly develop urinary tract tumors (Li 2024). So whether aristolochic acid directly drives these liver cancers is still being argued.The honest statement: for the kidney and upper urinary tract, causation is established; for liver cancer, the association is strong and causation is unsettled. The two do not carry the same certainty.
The rules did change. The 2020 Chinese Pharmacopoeia removed herbs containing aristolochic acid, with Asarum (Xi Xin) the exception (Li 2024). But old prescriptions, old stock and products from abroad still circulate, so names like Guan Mu Tong, Guang Fang Ji and Qing Mu Xiang are worth stopping at.
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Myth · Is it only counterfeits that cause harm
Between 1990 and 92, because of a manufacturing error, a batch of Belgian weight-loss formulas had Stephania tetrandra (fen fang ji), the intended herb, replaced by Aristolochia fangchi (guang fang ji). Both names contain "fang ji". The result was a group of women who went on to kidney failure, and then upper urinary tract urothelial carcinoma found across the group (Nortier 2000; IARC 2012).This is often told as a story about counterfeits hurting people. It is not.
Aristolochia fangchi is a genuine herbal medicine: it really was in pharmacopoeias, with its own name and growing regions. The problem was never whether it was genuine; it was that two herbs with similar names differ enormously in toxicity. When one is swapped for the other, the person doing the swapping may not know what they have swapped.
That is exactly what makes "only fakes cause trouble" so dangerous: it lets you believe that buying the genuine article, the expensive one or the old established brand makes you safe. Aristolochic acid does not care what you paid. Genuine Aristolochia is a Group 1 carcinogen too (IARC 2012).
So the question to ask is not "is this genuine?" but "what is actually in it?"
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Chapter 3
Why it hurt me and not them
The same herb: your uncle took it for ten years and was fine, you took it for three months and your liver got into trouble. That is not luck, and it is not a weak constitution. Often it comes down to the shape of a lock you carry.
Drug-induced liver injury (damage to liver cells caused by a medicine) has two tempers. One follows the dose: take enough and it harms anyone. The other is called idiosyncratic: it has little to do with dose or duration and everything to do with the person. He Shou Wu (Polygonum multiflorum) belongs to the second kind.
He Shou Wu is often taken to darken graying hair and to tonify the liver and kidneys. The US National Institutes of Health's database on drug-induced liver injury lists it as a well-established cause of clinically apparent liver injury (LiverTox 2020).
The lock is called HLA-B*35:01, a particular version of a molecule in the immune system. People who carry it have a much higher risk of liver injury from He Shou Wu than people who do not.
Drug-induced liver injury (damage to liver cells caused by a medicine) has two tempers. One follows the dose: take enough and it harms anyone. The other is called idiosyncratic: it has little to do with dose or duration and everything to do with the person. He Shou Wu (Polygonum multiflorum) belongs to the second kind.
He Shou Wu is often taken to darken graying hair and to tonify the liver and kidneys. The US National Institutes of Health's database on drug-induced liver injury lists it as a well-established cause of clinically apparent liver injury (LiverTox 2020).
The lock is called HLA-B*35:01, a particular version of a molecule in the immune system. People who carry it have a much higher risk of liver injury from He Shou Wu than people who do not.
Mechanism · Why it happened to me
Here is how the lock works. The surface of your cells carries a kind of display rack (HLA). Its job is to hold up fragments from inside the cell so the immune system can take a look: friend or enemy? The racks come in many shapes, and HLA-B*35:01 is one of them.Some component of He Shou Wu probably fits exactly into the groove of that particular shape. Once it is held up, the immune system does not recognize what it is seeing, so it attacks it along with the liver cell holding it. The liver cell becomes collateral damage.
The numbers are hard: among 26 patients with He Shou Wu liver injury, 88% carried at least one copy of HLA-B*35:01, compared with 12% of patients whose liver injury came from other drugs and 5% of healthy controls (Li 2019). The same study also followed 72 outpatients taking He Shou Wu for 4 weeks. Among carriers of this gene type, 37.5% developed a symptom-free rise in transaminases (blood tests that reflect liver cell damage), against 4.7% of non-carriers. So "why me?" has an answer: not a fake herb, not a weak body. Your immune system just happens to recognize it.
It is easy to read the He Shou Wu story as "Chinese medicine has a problem". It does not. This is a property of herbs in general and has nothing to do with culture.
Take an example from an entirely different tradition: ashwagandha, the flagship supplement of Indian Ayurveda, which sells very well in Europe and the US. The drug-induced liver injury networks of Iceland and the US reported 5 cases of cholestatic or mixed liver injury after 2 to 12 weeks of use (Björnsson 2020). India then reported a series of 23 cases, in which people who already had chronic liver disease had severe, even fatal, outcomes (Philips 2023).
The same script on a different continent: a plant regarded as a gentle tonic has real pharmacological activity, therefore real toxic risk, and therefore collides with certain people.
One practical note. By now you may want to be tested for HLA-B*35:01. It is not a routine test today, and most places cannot run it. So the realistic action is not a gene test first but this: do not take it long-term without monitoring, watch for symptoms, and have your liver function checked regularly. The time to onset can stretch from a few days to about 6 months, so you cannot judge safety by "I have taken it for a while and I am fine" (LiverTox 2020).
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Chapter 4
Danshen taken with warfarin
"Chinese and Western medicines taken together do not interfere with each other." With danshen and warfarin, that sentence is wrong enough to make you bleed.
Warfarin (an oral anticoagulant) has a very narrow therapeutic window: a little too much and you bleed, a little too little and you clot. Danshen (Salvia miltiorrhiza) is widely used for heart and blood-vessel disease, so many people meet both at once precisely because they have a heart or vessel problem.
They collide along two routes. Pharmacokinetically: in rat experiments, adding danshen raised warfarin's peak blood level and total exposure (AUC) and slowed its clearance (Chan 2001). Pharmacodynamically: danshen itself holds back platelet clumping, interferes with clotting and promotes fibrinolysis (the process that dissolves clots).
One route leaves more drug in the blood; the other thins the blood by itself. The review's conclusion leaves no room: people taking warfarin should avoid danshen (Chan 2001). The harder part is that other herbs do not all push warfarin the same way: some raise its effect and some lower it.
Warfarin (an oral anticoagulant) has a very narrow therapeutic window: a little too much and you bleed, a little too little and you clot. Danshen (Salvia miltiorrhiza) is widely used for heart and blood-vessel disease, so many people meet both at once precisely because they have a heart or vessel problem.
They collide along two routes. Pharmacokinetically: in rat experiments, adding danshen raised warfarin's peak blood level and total exposure (AUC) and slowed its clearance (Chan 2001). Pharmacodynamically: danshen itself holds back platelet clumping, interferes with clotting and promotes fibrinolysis (the process that dissolves clots).
One route leaves more drug in the blood; the other thins the blood by itself. The review's conclusion leaves no room: people taking warfarin should avoid danshen (Chan 2001). The harder part is that other herbs do not all push warfarin the same way: some raise its effect and some lower it.
Clinical · Which way herbs push warfarin
If herbs only ever thinned the blood, things would actually be simple: remember not to combine them and you are done. The real trouble is that the direction varies.All of these collide with warfarin:
Danshen pushes warfarin's effect up, with a risk of bleeding; the review collected 3 cases of serious bleeding after the two were combined (Chan 2001).American ginseng: a found it pulled warfarin's effect down (Yuan 2004). That is the opposite direction, and the risk on this side is not bleeding but clotting.Goji: there are case reports of a markedly raised (a blood test of how strongly the blood is anticoagulated; higher means more prone to bleeding) with bleeding (Rivera 2012).Natto: extremely rich in vitamin , so it works against warfarin.
So the conclusion is not "herbs thin your blood". It is that some push, some pull, the strength varies, and you cannot guess which. That is exactly why your doctor has to know: not so they can stop you, but so they know which way to adjust the dose and how often to test.
Grade the evidence honestly. Most of it here is case reports plus animal pharmacokinetics, not large randomized trials. That is enough to support the decision not to combine, because the downside is bleeding or clotting, which is too costly to gamble on. It is not enough for precise prediction: no one can tell you how much a given amount of danshen will raise your INR.
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Chapter 5
How the liver handles herb molecules
The word natural is printed for you to read, not for your liver.
The liver does not sort molecules by whether they came from a laboratory or were boiled out of a root. It reads only their structure. Every molecule with pharmacological activity goes down the same production line.
The first stage (phase I) often makes a molecule more dangerous: cytochrome P450 enzymes attach oxygen to it and often produce an intermediate that is more reactive than the original molecule (Guengerich 2008). The second stage (phase II) rescues the situation: conjugating enzymes weld glutathione (a small detoxifying molecule inside liver cells) onto that reactive spot so it can leave in bile or urine (Jancova 2010).
When things go wrong, it is almost always the same thing: the first stage runs faster than the second. That is how a paracetamol overdose damages the liver, and it is also how aristolochic acid harms the kidney and leaves its signature on DNA.
The liver does not sort molecules by whether they came from a laboratory or were boiled out of a root. It reads only their structure. Every molecule with pharmacological activity goes down the same production line.
The first stage (phase I) often makes a molecule more dangerous: cytochrome P450 enzymes attach oxygen to it and often produce an intermediate that is more reactive than the original molecule (Guengerich 2008). The second stage (phase II) rescues the situation: conjugating enzymes weld glutathione (a small detoxifying molecule inside liver cells) onto that reactive spot so it can leave in bile or urine (Jancova 2010).
When things go wrong, it is almost always the same thing: the first stage runs faster than the second. That is how a paracetamol overdose damages the liver, and it is also how aristolochic acid harms the kidney and leaves its signature on DNA.
Clinical · Why doctors miss it too
Natural buys nothing on this production line. If anything it cuts the other way: a plant often has medicinal effects precisely because it evolved molecules that interfere with animal physiology, originally as a defense against insects. This was never a contest between Chinese and Western medicine; it is pharmacology against a body.This production line is also hard to see in the statistics, and the reason is again built into how it works.
Drug-induced liver injury has no single lab test that settles it. It is a diagnosis of exclusion: only after viral hepatitis, alcohol, autoimmune disease and bile duct blockage have been ruled out does suspicion fall on a drug. That means the doctor has to know what you took before they can suspect it at all.
But many people do not say. In a US national survey, only about one third of people who used herbs or supplements had told their doctor, and across every group studied, telling the doctor was the exception rather than the rule (Kennedy 2008). These are US data and do not carry straight over to China, but the psychology is shared: you do not think of it as a drug, so you do not think it needs mentioning.
So a loop closes. You believe Chinese medicine is naturally harmless, so you do not tell your doctor; the doctor does not think to look there, and the cause is recorded as unknown; the share of Chinese medicine in the statistics is pushed down, and it looks safer.
For background: in a study covering mainland China, among liver-injury cases with an identified cause, the largest single category was traditional Chinese medicine together with herbal and dietary supplements (26.81%), with anti-tuberculosis drugs second (21.99%) (Shen 2019). That is a breakdown of causes, not a poisoning rate: in a population that uses Chinese medicine so widely the denominators differ, so it cannot be read as a direct comparison of toxicity. It settles exactly one thing, and that one thing is enough: if Chinese medicine were truly gentle on the liver by nature, it could not be at the top of that list.
Breaking the loop takes one extra sentence in the consulting room: "I am taking these herbs and supplements."
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Chapter 6
How to use herbs more safely
The single most useful step costs nothing and needs no pharmacology: let your doctor know what you are taking.
1. Say it yourself; do not wait to be asked. List Chinese medicines, health supplements, herbal teas and any formula a relative gave you (Kennedy 2008).
2. Stop and check when you see Guan Mu Tong, Guang Fang Ji or Qing Mu Xiang. These are sources of a Group 1 carcinogen (IARC 2012).
3. Stop herbs around the time of surgery; ask the anesthetist and the surgeon how long before (Ang-Lee 2001).
4. Be especially sure to mention them if you take anticoagulants, diabetes drugs, immunosuppressants, anti-rejection drugs or antiepileptics (Chan 2001).
5. Do not take them long-term without monitoring. Liver injury from He Shou Wu can appear anywhere from a few days to about 6 months after starting (LiverTox 2020).
Red flags: yellowing of the skin or the whites of the eyes, urine as dark as strong tea, persistent tiredness, nausea, pain in the upper right abdomen. Get your liver function checked right away (LiverTox 2020).
1. Say it yourself; do not wait to be asked. List Chinese medicines, health supplements, herbal teas and any formula a relative gave you (Kennedy 2008).
2. Stop and check when you see Guan Mu Tong, Guang Fang Ji or Qing Mu Xiang. These are sources of a Group 1 carcinogen (IARC 2012).
3. Stop herbs around the time of surgery; ask the anesthetist and the surgeon how long before (Ang-Lee 2001).
4. Be especially sure to mention them if you take anticoagulants, diabetes drugs, immunosuppressants, anti-rejection drugs or antiepileptics (Chan 2001).
5. Do not take them long-term without monitoring. Liver injury from He Shou Wu can appear anywhere from a few days to about 6 months after starting (LiverTox 2020).
Red flags: yellowing of the skin or the whites of the eyes, urine as dark as strong tea, persistent tiredness, nausea, pain in the upper right abdomen. Get your liver function checked right away (LiverTox 2020).
In practice · Treat herbs as medicine
Be especially sure to mention it if you take anticoagulants, diabetes drugs, immunosuppressants, anti-rejection drugs or antiepileptics: what they have in common is a narrow therapeutic window that cannot absorb an unexplained variable (Chan 2001).The red flags once more. This is the most typical set of signs of drug-induced liver injury, and they often come in this order: tiredness and nausea first, then dark urine and yellowing (LiverTox 2020). Among clinically apparent cases of liver injury from He Shou Wu, about 10% ended in death or needed an urgent liver transplant. That is not scaremongering; it is the reason this has to be dealt with now rather than some other day (LiverTox 2020). Stop the herb and see a doctor; do not watch it for a few more days on your own. The 2020 Chinese Pharmacopoeia removed herbs containing aristolochic acid (Asarum excepted), but old prescriptions, old stock and products from abroad are still in circulation (Li 2024). If you are unsure, ask the pharmacist: is there anything from the Aristolochia family in this?
This story in one sentence: it is not asking you to avoid Chinese medicine; it is asking you to treat it as medicine.
What does medicine mean? It means there is a dose, there are interactions, people differ, there are conditions for it to work, there are reasons to stop, and there are red flags. The caution you bring to a pharmaceutical without thinking, reading the leaflet, asking the doctor, watching for side effects, carries over to herbs unchanged.
Why is it worth it? Because every item in this story can be avoided:
The cancers from aristolochic acid can be avoided by reading a name (IARC 2012).The bleeding from danshen with warfarin can be avoided by saying one sentence (Chan 2001).Liver injury from He Shou Wu can be caught early by checking liver function and knowing the red flags (LiverTox 2020).
None of them asks you to give up a belief. Each asks only for one more action.
Finally, the title's sentence, finished:
Natural does not mean safe. But natural does not mean dangerous either. It simply does not mean anything.
Origin cannot certify safety, whether it is willow bark or a laboratory. Safety is earned one piece of evidence at a time: who took it, for how long, what happened, and what it collided with. Artemisinin earned it, which is why it has saved millions of lives. Aristolochic acid was investigated just as thoroughly, which is why it is on the Group 1 carcinogen list. Both were measured with the same ruler, and that ruler is evidence, not allegiance.
This story is education to help you understand the why; it is not medical advice. Whether to stop something, how to stop it and whether to get tested: ask your doctor.
References · 16
- Cohen, P. A., Avula, B., & Khan, I. A. (2017). Variability in strength of red yeast rice supplements purchased from mainstream retailers. European Journal of Preventive Cardiology, 24(13), 1431-1434. 28 brands analysed by UHPLC-DAD-QToF; monacolin K undetectable in 2, and across the remaining 26 it ranged 0.09-5.48 mg per 1200 mg of red yeast rice — 0.09 to 10.94 mg per day at the manufacturers' own recommended servings (a 120-fold spread). 10.1177/2047487317715714
- EFSA Panel on Food Additives and Nutrient Sources added to Food. (2018). Scientific opinion on the safety of monacolin K from red yeast rice. EFSA Journal, 16(8), 5368. 10.2903/j.efsa.2018.5368
- Ernst, E. (2002). Toxic heavy metals and undeclared drugs in Asian herbal medicines. Trends in Pharmacological Sciences, 23(3), 136-139. 10.1016/S0165-6147(00)01972-6
- Zhang, L., Yan, J., Liu, X., Ye, Z., Yang, X., Meyboom, R., et al. (2012). Pharmacovigilance practice and risk control of traditional Chinese medicine drugs in China: current status and future perspective. Journal of Ethnopharmacology, 140(3), 519-525. Abstract: China's adverse drug reaction monitoring system, voluntary reporting since 1989, covers both Western and TCM drugs; about 10-15% of the ADR reports received by the National Center relate to TCM drugs, mainly formulated products; serious or multi-case reports appear in the Chinese ADR Information Bulletin, and the SFDA can suspend a preparation (abstract, PMID 22374080). 10.1016/j.jep.2012.01.058
- International Agency for Research on Cancer. (2012). Aristolochic acids and plants containing aristolochic acids. In IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 100A: Pharmaceuticals. Lyon: IARC. Both aristolochic acid and plants containing aristolochic acid are classified Group 1 - carcinogenic to humans. www.ncbi.nlm.nih.gov/books/NBK304331
- Han, J., Xian, Z., Zhang, Y., Liu, J., & Liang, A. (2019). Systematic overview of aristolochic acids: nephrotoxicity, carcinogenicity, and underlying mechanisms. Frontiers in Pharmacology, 10, 648. 10.3389/fphar.2019.00648
- Poon, S. L., Pang, S.-T., McPherson, J. R., et al. (2013). Genome-wide mutational signatures of aristolochic acid and its application as a screening tool. Science Translational Medicine, 5(197), 197ra101. 72% of mutations were A:T-to-T:A transversions - a signature distinctive to aristolochic acid. 10.1126/scitranslmed.3006086
- Hoang, M. L., Chen, C.-H., Sidorenko, V. S., He, J., Dickman, K. G., Yun, B. H., et al. (2013). Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing. Science Translational Medicine, 5(197), 197ra102. Whole-EXOME sequencing of upper urinary tract urothelial carcinomas from 19 patients with documented aristolochic acid exposure: most of the mutations (72%) in these tumors were A:T-to-T:A transversions. 10.1126/scitranslmed.3006200
- National Institute of Diabetes and Digestive and Kidney Diseases. (2020). Polygonum multiflorum. In LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: NIDDK. Likelihood score A; latency a few days to ~6 months; ~10% of clinically apparent cases were fatal or required urgent liver transplantation. www.ncbi.nlm.nih.gov/books/NBK548795
- Li, C., Rao, T., Chen, X., Zou, Z., Wei, A., Tang, J., et al. (2019). HLA-B*35:01 allele is a potential biomarker for predicting Polygonum multiflorum-induced liver injury in humans. Hepatology, 70(1), 346-357. 88% of 26 cases carried at least one copy versus 12% of other-DILI patients and 5% of controls. Abstract: MHC sequencing of 11 Polygonum multiflorum liver-injury patients found HLA-B*35:01 in 45.4% vs 2.7% of the Han Chinese population (OR 30.4); a replication with 15 cases vs 33 other-DILI patients and 99 population controls confirmed it (OR 86.5 and 143.9); in a prospective cohort of 72 outpatients taking the herb for 4 weeks, 6 developed asymptomatic transaminase rises, 37.5% of carriers vs 4.7% of non-carriers (RR 8.0). The 88% / 12% / 5% carrier figures above are not in the abstract (abstract, PMID 30985007). 10.1002/hep.30660
- Chan, T. Y. K. (2001). Interaction between warfarin and danshen (Salvia miltiorrhiza). Annals of Pharmacotherapy, 35(4), 501-504. Three published cases of serious bleeding on warfarin plus danshen; danshen increased AUC and half-life of both R- and S-warfarin while decreasing clearance, and additionally inhibits platelet aggregation with antithrombin-III-like activity. 10.1345/aph.19029
- Guengerich, F. P. (2008). Cytochrome P450 and chemical toxicology. Chemical Research in Toxicology, 21(1), 70–83. 10.1021/tx700079z
- Jancova, P., Anzenbacher, P., & Anzenbacherova, E. (2010). Phase II drug metabolizing enzymes. Biomedical Papers, 154(2), 103–116. 10.5507/bp.2010.017
- Kennedy, J., Wang, C.-C., & Wu, C.-H. (2008). Patient disclosure about herb and supplement use among adults in the US. Evidence-Based Complementary and Alternative Medicine, 5(4), 451-456. Approximately one-third of herb/supplement users disclosed their use to a physician. 10.1093/ecam/nem045
- Li, C., Li, X., Niu, M., Xiao, D., Luo, Y., Wang, Y., et al. (2024). Unveiling correlations between aristolochic acids and liver cancer: spatiotemporal heterogeneity phenomenon. Chinese Medicine, 19, 132. Argues the AA mutational signature in HCC marks exposure rather than proving causation. Notes the 2020 Chinese Pharmacopoeia deleted AA-containing herbal medicines, except Asarum. 10.1186/s13020-024-01003-y
- Ang-Lee, M. K., Moss, J., & Yuan, C.-S. (2001). Herbal medicines and perioperative care. JAMA, 286(2), 208-216. Recommends herbal medicines generally be discontinued preoperatively, with 2 weeks suggested for most. pubmed.ncbi.nlm.nih.gov/11448284