https://www.researchgate.net/profile/Chirag_Patel103/publication/318228070_Synergistic_inhibition_of_glioma_cell_proliferation_by_Withaferin_A_and_tumor_treating_fields/links/5a01c1304585152c9db37152/Synergistic-inhibition-of-glioma-cell-proliferation-by-Withaferin-A-and-tumor-treating-fields.pdf?origin=publication_detail
Friday, 5 April 2019
Withaferin A (Ashwagandha) & TTF
Came across this study which may be of interest to Optune users. Stephen (and other scientifically literate folks) when you have time would be grateful for your thoughts about the science and its relevance to human application. Would also be interested to hear about people’s experience with Ashwagandha. Thanks!!
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I've said this before, but I put very little weight on cell culture studies, because they completely bypass the question of pharmacokinetics (bioavailability, metabolism, and achievable plasma or tissue concentrations of the drug) and toxicity. There are very few things that wouldn't kill cancer cells (or any cells) if you used a high enough concentration, but the question remains whether x concentration of a drug is even achievable in a living body without killing the subject, or causing severe toxicity. This matter is especially complicated when speaking of brain tumors, which are protected by an at least partially intact blood-brain barrier.
ReplyDeleteFortunately, we do have recent human pharmacokinetic data for withaferin A, which was tested in a phase 1 trial for osteosarcoma.
https://reader.elsevier.com/reader/sd/pii/S0975947618307897?token=2C44A6DE32D313FF3DD839A0560AD503138A87F0D314FDE9307611F3181C231194FB5EF9BEB4AE0AB4207C5922E412F5
Safety and Pharmacokinetics of Withaferin-A in advanced stage high grade Osteosarcoma: A phase I trial
The patients were given withaferin-A (not ashwagandha) in doses of 72 - 216 mg. But "There were no detectablelevels of Withaferin-A in any of the [blood] samples collected." And "WA appears to have low oral bioavailability". But "Further studies with improved formulations are warranted."
This is a classic example of why cell culture studies that appear promising in the lab don't translate into humans.
Withaferin-A only makes up a small percentage of ashwagandha preparations (0.017 - 2%). If withaferin-A content of your ashwagandha supplement was even a generous 1%, you would need to consume 7.2 to 21.6 grams of it to get the doses of withaferin A used in the human study above (and I would strongly discourage this, not only for safety reasons, but because as we've seen there was no detectable withaferin-A found in plasma at these oral doses.
There are other reasons to take ashwagandha, for example effects on immune cells.
http://astrocytomaoptions.com/re-educating-the-immune-system/
But the evidence for a direct effect of withaferin-a in humans considering its low or non-existent oral bioavailability, and the low withaferin-a content of ashwagandha, is not looking too great.
Just reading the fine print of the human study I linked to. They were taking AshwaMAX with a withaferin-A content of 4.5%. The highest dose cohort was taking 4 capsules three times daily, for a AshwaMAX dose of 4800 mg (containing 216 mg of withaferin A). They didn't use higher doses ("but the total dose is limited by the number of capsules apatient can reasonably consume in a day").
DeleteOne limitation of the study is that the analytic technique they used to detect withaferin-A in plasma was quoted as having a sensitivity of 50 ng/ml, which is not very sensitive (50 ng/ml of withaferin A would translate to 106 nanomolar). This implies that there may have been some withaferin-A in the collected plasma samples, but at a concentration lower than 100 nanomolar.
"more sensitive analytical techniques are required to characterize the PK [pharmacokinetics] of WA in humans. We could not establish bioavailability of WA due to the above reasons"
Warm thanks for your quick and incredibly helpful response. I will read cell culture studies with a more critical eye moving forward. You’re the best! —Sharon
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