PSA going down, but ALP increasing

[rsgdmd]

I'm 3 weeks into a clinical trial for ARV-766, an AR degrader. At 2 weeks, my PSA had dropped from 133 to 66! Bone pain is much less. All my liver numbers are fine, but alkaline phosphatase has gone from 199 when I started to 429 at two weeks and 519 at three weeks. Doc thinks may just be a surge, but this is a pretty big surge. Any thoughts?

[swwags]

ALP is associated with bone disorders and liver damage. Seems possible that the trial is giving you fits and not something organic. 199 is high too though. what kind of tests did you have done to drill down on 199 before you entered the trial? Normal ALP is 36-125. Do you have a link to the trial?

[God_Loves_Me]

Rising ALP and declining PSA - Liver stressed.

[God_Loves_Me]

In my opinion, Call immediately to medical triage line of clinical trial center and let them know about your concerns. It is good medicine and they will figure out for liver stress.

[rsgdmd]

So, all my other liver numbers are largely unchanged. Bilirubin and albumin are normal. ALT and AST are both a little low, but have been for a few months. Here's link to the trial: clinicaltrials.gov/study/NC...

[Justfor_]

It can be debris from bone metastases. You can check this (optimistic) hypothesis by having a bone ALP count to compare against total ALP.

[rsgdmd in reply to Justfor_]

Good idea. Having that done tomorrow.

[jeetu_g27]

ncbi.nlm.nih.gov/pmc/articl... link to a case study where a patient ALP gone to 3000 while PSA being decline . Though all cases are different, hope it may help a bit

[Grandpa4]

thinking liver toxicity. Seems awfully fast for bone Mets. Especially when your pain is better.

[rsgdmd]

So, My ALP is still very high, but Dr did additional tests, which all showed no issues with the liver. Had Gamma Glutamyl Transpeptidase, which was normal. Had ALKALINE PHOSPHATASE ISOENZYMES, which showed ALP of 542, but bone isoenzyme a little high, liver isoenzyme is normal. Increase in ALP is known side effect of ARV-766; so is elevated ALT, AST - mine are normal.

[Justfor_ in reply to rsgdmd]

Milk thistle lowered my ALT and AST to a nadir of the latest 20-30 years that I keep records on. Noticing this it became my #1 supplement.

[Tinkudi in reply to Justfor_]

What dose of milk thistle did you take

[Justfor_ in reply to Tinkudi]

One of these, every evening with my Atorvastatine/Ezetimibe

amazon.com/Life-Extension-E...

[Seasid in reply to Justfor_]

What is the daily dose of silymarin you are taking?

[Justfor_ in reply to Seasid]

One gel per day, so half what you read on the photo.

Life Extention Advanced Milk Thistle

[Seasid in reply to Justfor_]

Do you know that it may be a very good PARP inhibitor according some Indian research study?

[Seasid in reply to Justfor_]

Do you know what is the recommended maximum daily dose of silymarin per day without toxicity?

[Justfor_ in reply to Seasid]

Sorry no. What I only have read, though coming from Life Extension, is that the potent anti-cancer compounds of the mix are the isosilybins and it is just for this reason that they explicitly mention their quantities. You may run it through AI to see if there is third party confirmation on this claim.

[Seasid in reply to Justfor_]

Silybin and silymarin are both derived from the milk thistle plant (*Silybum marianum*), but they are not the same. Understanding their differences, especially regarding their anticancer properties, can be crucial.

### Silymarin

- **Composition**: Silymarin is a complex mixture of flavonolignans, including silybin (also known as silibinin), isosilybin, silychristin, and silydianin. Silybin is the most abundant and active component, making up about 50-70% of silymarin.

- **General Properties**: Silymarin is widely known for its hepatoprotective effects and antioxidant properties. It has been used to treat liver disorders like cirrhosis, hepatitis, and fatty liver.

- **Anticancer Properties**: Silymarin exhibits a broad range of anticancer effects, including inhibition of cancer cell proliferation, induction of apoptosis (programmed cell death), and suppression of angiogenesis (formation of new blood vessels in tumors). Silymarin’s antioxidant activity also helps protect cells from oxidative stress, which is linked to cancer progression. However, its efficacy can vary depending on the cancer type and the bioavailability of its components.

### Silybin (Silibinin)

- **Composition**: Silybin is the most potent and biologically active component of silymarin. It exists as two diastereomers, silybin A and silybin B.

- **General Properties**: While it shares many of the hepatoprotective and antioxidant benefits of silymarin, silybin has been studied more extensively for its specific anticancer effects.

- **Anticancer Properties**: Silybin has demonstrated stronger anticancer activity compared to the full silymarin complex. It has been shown to inhibit cancer cell growth, induce apoptosis, and interfere with cancer cell signaling pathways. Silybin can also enhance the efficacy of certain chemotherapy drugs and reduce their toxicity. Studies have highlighted its potential in treating various cancers, including prostate, breast, lung, and colon cancers. It’s particularly noted for its ability to inhibit the metastatic spread of cancer cells.

### Comparison and Conclusion

- **Bioavailability**: One challenge with both silymarin and silybin is their low bioavailability when taken orally. Formulations to improve absorption, such as silybin-phosphatidylcholine complexes (like Siliphos®), have been developed to address this issue, with silybin-based formulations often showing more potent effects.

- **Potency**: Silybin is generally considered more potent than the whole silymarin complex in terms of anticancer activity, largely due to its higher concentration and direct effects on cancer cells. However, silymarin’s synergistic components might offer broader protective effects in some contexts.

In summary, while silymarin as a whole has anticancer properties, silybin stands out as the more potent component for targeting cancer cells directly.

[No_stone_unturned in reply to Justfor_]

Me too