EGCG could be a culprit too. I’ve definitely read of cases of acute injury I believe when taken at above 500-700mg. Perhaps check your dosage.

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RTHR, I submitted your list of supplements to ChatGPT and asked, “Which of the preceding supplements would be the most likely culprits for liver damage?” The ChatGPT answer was, " Among the supplements listed, berberine, curcumin, and EGCG (epigallocatechin gallate) are the most likely to contribute to potential liver damage, especially at higher doses or in susceptible individuals."

ChatGPT provided too much detail about your total list to show here, but you could go to chatgpt.com and ask the same question if you want all the details.

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I had a similar concern but it likely turns out the culprit is one of my medications rather than supplements (or environmental exposures).

I was taking 15-20 supplements/day, as @Jay suggested ran them all past Claude.ai pro and ChatGP (via perplexity.ai pro). None were indicated for liver function test elevation. But a rare (~1%) impact from a medication was indicated. Titrating that med down now and feeling confident it’s the cause.

Doc’s were funny about it: cut back your alcohol (I don’t drink), lose weight (I’m 4 months at a healthy BMI and <15% body fat), don’t get environmental exposures (nothing changed in that front).

Me: what about this relatively rare but FDA recognized / labeled risk for one of the only meds I take?
Dr: who knows, let’s see what a gastroenterologist says if you can get an appointment soon.
Me: How about a hepatologist?
Dr: here’s your gastroenterologist referral.

Interestingly, in addition to progressively elevating ALT and AST I had elevated SHBG and related hormone impacts (lower free T because SHBG binds to and reduces it, higher LH probably trying to make up for the low free T). I understand that liver insult results in increased SHBG production so it appears these are all related.

So are you taking any meds or have potentially any environmental or diet exposures which could be impacting liver function tests? Recently sick or heavily stressed?

700+ is remarkably elevated, hope you’re working with your doctor closely to address that.

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Acarbose contains Chromium. A patch test years ago showed I was allergic to Chromium. I don’t know if that could have caused the problems you had with it.

I found an extract of white beans that contains the same thing minus the Chromium. I used to take one like it about 10 years ago; it was very cheap and didn’t carry any of the warnings on Acarbose. I think the warnings are there because they are afraid people will take it with glucose-lowering drugs, like Metformin, and go into ketoacidosis. The one I take is just called an “extract of white beans.”

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Thank you @zebit0
I am now doing IV injection with glutathione and magnesium isoglycyrrhizate.
And my doctor suggests to stop all the supplement from now on.
So may be I’ll stop taking ang prescribed drug for antiaging and switching to a simplified protocol just like Brad Standfield and Siim Land, focusing on exercise diet and sleep.

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Biohacker’s best friend, Life Extension CMP blood test for just $35:

Biohacker’s 2nd best friend, a spreadsheet to track your labs alongside your supplements and dosages: Blood Markers, Levine Phenotypic Age & Supplements (Public) - Google Sheets

You should get a blood draw at least monthly when you’re on an extensive regimen like yours. Anything and everything can raise liver enzymes, or make your kidney markers worse, based on my personal experience.

As for bonus content, the spreadsheet also computes your Levine phenotypic (biological) age for every blood draw! Highly recommended.

You should just go back to zero. Wait for everything to heal. Then start adding things one or two a time. Measure the effects for 1-2 months, then add more. Monthly tracking is essential. You can do every two weeks if you’re paranoid (or have health issues) — I do! I’ve collected over 100 blood test results in the past 4 yrs, and learned a whole lot about my body’s response. No textbook or academic publication predicted what I’ve seen (e.g. acarbose causes my liver enzymes to increase beyond normal. Same with curcumin. Presumably because so many things are stacked on top of each other).

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Berberine and curcumin significantly influence liver CYP enzymes, particularly CYP3A4. This means that medications metabolized via CYP enzymes may accumulate in the body.

Berberine can affect the levels of rapamycin, for example, through the CYP3A4 enzyme.

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i take all the potential liver damage supplements daily from ashwagandha 500mg, circumin, gree tea powder, etc. but my ALT stayed under 19. (15-19 for 4 years)

NAC may play a role to help keep my ALT low, since Covid19 ( around 2019 ) i begin to take NAC and later together with Glycerin daily. Before i regularly take NAC, my 2018 blood test ALT was 29.

A paper said NAC+Glycine can help to produce glutathione, a powerful antioxidant to prevent liver damage and repair liver failure.

p.s. i also drink.

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I test often so looked for best pricing this last 12 months. Marek Health & UltraLabs are affordable; but Fitomics has been significantly cheaper. All get tests from LabCorp and the only differences are Fitomics is cheaper (often by about half) and has a month subscription fee of $30. I save that much every time I test.

For example, the same CMP is $6.98

My liver related weekly tests are under $23 with a 10% coupon for:
Ferritin $4.98
CK $4.54
GGT $3.98
CMP $6.58
CBC $4.58

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What source and form of glutathione are you taking?
Those are impressive liver function test results.

NOW NAC 1g and Now glycine 1g from iHerb, 2g NAC and 4g Glycine daily, but I have doubt that lower the rapamycin effect too…

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Sorry to hear this. I’ve seen case reports that each one of these have caused liver injury, but it’s unclear what it is. I haven’t looked at the others. I’ve avoided herbal supplements for this reason like it’s the plague. If you want do give us an update how you’re doing later.

If I were you I would also quit all other drugs except those prescribed by the doctor. Diet, exercise, and sleep only.

In general, plant polyphenols / phytochemicals (especially in high concentrations) can be problematic, because they don’t have a role to play in normal human biology (i.e. they don’t get incorporated into our cells/tissues) although they do effect certain pathways. They are foreign molecules to us. However, in my view, the right ones at the right doses (and sometimes, in whole food matrix) can be beneficial in 3 contexts:

  1. as a hormetic/beneficial stressor on the body, for elevating glutathione or other mediators, or
  2. for feeding the microbiome, or
  3. for a specific medicinal or therapeutic use case
    Have I missed anything?

From a hormetic standpoint, rather than molecular hormesis (i.e. using a whole bunch of plant compounts like Ashwagandha, Curcumin, EGCG & an endless list). I’d rather use more of environmental hormesis (i.e. exercise, cold exposure, heat from sauna, breath work, sun UV exposure at the right time of the day, and fasting), which are natural ways to stress the body that have evolutionarily driven primates/humans to become resilient through the ages.

From a nutritional standpoint, my personal view is that animal source derived supplements (of course, right brand / quality / dose) are far safer, and bioavailable for humans. E.g. fish oil, dessicated organs, dessicated fish roe, oyster extract, whey protein, probiotics, bone broth powder, etc. Our biology will readily consume, utilize and incorporate these compounds, as they are compatable to us (generally speaking, not accounting for allergies for some, and not factoring personal dietary choices).

Btw, my supplement coaktail does include quite a few plant-derived molecules. There may be some benefits to these, however, I think that plant extracts warrant a greater level of caution, when it comes to toxicity, especially for those with genetic susceptibilities (e.g. sub-optimal MTHFR, CYP family of genes, etc), and also considering potential cross-reactivity between compounds (which are very hard to determine & can be highly bio-individual).

When it comes to plant compounds, rather then concentrated extracts, I suggest you consume them as part of your whole foods, as far as possible. E.g. coffee (rather than caffeine extract), tea (rather than EGCG extract), curry powder (rather than circummin extract), etc.

To keep this discussion more relevant, I’m ignoring pharmaceuticals (most of which are plant-derived).

Any thoughts?

Generally agree to your overall point that polyphenols should be taken carefully and it is possible to have too much (and that cutoff can vary from person to person). I’ll add that there are some specific molecules found in plants like carotenoids (Zeaxanthon, Lutein, Lycopene, Astaxanthin) that generally don’t have the same issue and can be taken more broadly at recommended/researched doses.

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I’m shocked to see this. I’d guess one of the things you’re taking isn’t safe. Have you had your GGT tested? That’s a much more reliable liver test. I’d say it’s imperative that you check your GGT next time you look at your live enzymes.

They will also add any LabCorp test you ask for to their catalog within a day. I’ve had them add sirolimus, lithium, and three better quality testosterone tests.

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Those are some serious liver enzyme elevations. Would stop everything and repeat weekly. My money is on the supplements which can be contaminated with many things. And always hard to know where they are sourced from. Lots of reports in the literature about these kinds of problems. I take all the bullet point stuff including twice the dose of rapa and 6x the acarbose and my LFTs have not budged.
Don’t know what you mean by ‘1.5g of plant extract’…is that product.

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Thanks a lot.

I’ve been taking prescription medicines for almost 2 weeks, and liver enzymes are much lower. It may still needs a few weeks to fully recover.

Medicines I am taking now are Silymarin and Diammonium Glycyrrhizinate.

Theoretically liver needs 2-3 month to grow back well.
I can’t do too much exercise during my recovery period, nor can I take any anti-aging suuplements.
I will do some tests especially the liver and kidney functions biweekly from now on.

My lesson learned are:
Test more frequently,
Kitchen sink is not for me.

The supplement or drug that caused liver injury is not clear yet.
My doctor believes it was those plant extract, either the dosage was too high that they depleted glutathione in liver, or my liver can’t metabolize them correctly (could be genetic problem, I haven’t tested yet).
Many plant active ingredients like EGCG or Cucurmin would increase ROS. People with HLA-B*35:01 would be more sensitive to these polyphenols.
Acarbose may slightly hurt liver so I won’t take it any more.

A few month later, my antiaging stack will be simplified to the Rhonda Patrick, Brad Standfield and Siim Land’s version.
Exercise, sleep and diet.
VD+K, Magnesium, Omega 3.
Some supplement that is mild to liver may be worth considering too.

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Have you actually had your liver checked? For example, ultrasound? With a spike in enzymes that high, it suggests quite significant toxicity.

How about albumin, gamma GT, bilirubin etc? Were they also altered?

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Berberine is an inhibitor of CYP2D6, with an IC50 value of approximately 11.9 µM3. This inhibition is quasi-irreversible, meaning that once the enzyme is inactivated, new enzyme must be synthesized to restore activity.

CYP2D6 can also be activated by drugs, which leads to increased absorption-metabolism of substates like codeine into morphine, tramadol into desmethyltramadol, oxycodone into oxymorphone.

It is easy to see how side effects occur due to our genetic profile. I really look forward to AI-driven personalized medicine.

Guidelines – CPIC

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