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Sunday, 26 July 2015

Withania somnifera (ashwagandha) inhibits tumor growth in rat glioma model

Withania somnifera Suppresses Tumor Growth of Intracranial Allograft of Glioma Cells

In this study, oral administration of an ashwagandha water extract to rats bearing C6 gliomas for 21 days significantly inhibited tumor volume.  The dose of ashwagandha was equivalent to 140mg/kg dry matter.  Using the allometric scaling method that would be in the neighborhood of 1500 mg of ashwagandha (dry matter), but allometric scaling is a pretty unreliable method to determine equivalent human doses.

I've uploaded the study to the Brain Tumor Library on Google Drive.  Let me know if you want access to the library.

See my update on the Supplements page at Astrocytoma Options.

Stephen
at

20 comments:

  1. Unknown28 July 2015 at 17:15

    Hi this is Lycka, I need to make a new gmail account.
    Interesting article, do you know which brand is good. Would the Life Extension brand be good enough? That brand uses the root and the leafs

    ReplyDelete
  2. Stephen W29 July 2015 at 12:26

    Yes, the Life Extension product contains Sensoril (TM) ashwagandha.

    http://sensoril.com/why-sensoril/

    This product claims to have the highest concentration of "bioactive" ashwagandha consitutents. The product was designed to reduce stress etc., not for cancer, but it is the best product that I'm aware of, and also includes leaf extract (the study I referenced above used a leaf extract). I think the Life Extension/ Sensoril product is a good choice.

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  3. Predrag29 July 2015 at 23:09

    Hi All,
    for European readers it might be easier to get Nutrisan's Sensoril Product.
    http://www.nutrisan.com/en/sensoril-474.htm

    To my understanding Sensoril is just the brand that both products are using. The Nutrisan's version has 150 mg per capsule. It also mentioned 0.5% withaferine A but I'm sure that this is the case also for the product from Life Extension.

    My wife is taking for her low grade brainstem glioma 2 capsules per day. But I guess that this is not enough. Any ideas on the dosing? Should we consider 1500 mg /150 mg = 10 capsules?

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    Replies
    1. Unknown31 July 2015 at 12:12

      Hi Predrag, have you looked at the Swanson brand? They're on Amazon and a good price, Swanson seem to come out well on quality tests.

      Delete
  4. Stephen W30 July 2015 at 12:07

    In the discussion section of the rat study (above), they say that the major constituents of ashwagandha water extract (air dried) is 650.5 ng withanone per mg dried extract, and 561 ng withaferin A. That would mean the dried extract is only 0.065% withanone and 0.056%.

    If Sensoril really has 0.5% withaferin A, that is about 9 times higher withaferin A content than the dried ashwagandha water extract.

    It's always tricky to try to extrapolate a human dose from a rodent dose, but assuming the effects of ashwagandha are dose-dependent, the more the better. The questions always arise "how much can I tolerate" and "how much can I afford?"

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  5. Michael W29 September 2015 at 09:20

    Stephen

    is the C6 glioma a GBM cell or is it a lower grade glioma cell. Seems to me its GBM, but never occurred to me to ask.

    ReplyDelete
  6. Stephen W29 September 2015 at 09:59

    C6 is not a human glioma at all, but a rat glioma, induced by repeated injections of methylnitrosourea (a carcinogen) to outbred Wistar rats.

    http://www.atcc.org/products/all/CCL-107.aspx#generalinformation

    http://www.ncbi.nlm.nih.gov/pubmed/12457224

    Generally used as a model for GBM and can be grown in wild-type Wistar rats and other rat strains.

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  7. Unknown26 November 2015 at 08:25

    so which brand has the highest potency? I want to order some tonight, but don't know which one?
    lycka

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    Replies
    1. Stephen W26 November 2015 at 09:53

      Life Extension has 125 mg Sensoril per capsule. Nutrisan has 150mg Sensoril per capsule. The potency is the same, but you get a slightly higher amount per serving in the Nutrisan product.

      http://www.nutrisan.com/en/sensoril-474.htm

      http://www.lifeextension.com/vitamins-supplements/item00888/optimized-ashwagandha-extract-stimulant-free

      Delete
    2. Unknown26 November 2015 at 12:57

      THANKS!

      Delete
  8. Unknown26 November 2015 at 13:00

    How much capsules would you recommend for someone who weighs 84 kg?

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    Replies
    1. Stephen W26 November 2015 at 14:19

      For relief of stress and fatigue, as little as 125mg of Sensoril was effective. But anti-cancer effects probably require higher doses. 500 mg per day? Very little human evidence to go on.

      Delete
  9. Anonymous10 June 2017 at 18:03

    I've procured 4x 50g of ashwagandha leaf extract (from http://thehappyherbshop.3dcartstores.com/Ashwagandha_p_10.html) and am now looking at preapration methods for my 4-year-old, who has just been diagnosed with anaplastic astrocytoma of the pons (DIPG).

    The original study used dried leaf, but I think what I bought is powdered root (it's a very light beige, no hint of green).

    I had a taste of the powder and it's not exactly tasty. Any ideas around how I could make this both palatable and hopefully effective for my kiddo?

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    1. Anonymous10 June 2017 at 18:44

      According to this article, the highest concentration is derived from a simple water extraction process of 1:8
      www.greenpharmacy.info/index.php/ijgp/article/view/143/138


      I've mixed 50g of powder with 400ml of water and will let it sit for 10 hours as described. This should yield a concentration of almost 17%

      Delete
    2. Stephen W11 June 2017 at 04:56

      This is a bit off-topic to your question, but please see my recent post on the drug ONC201 expanded access for H3-mutant gliomas. The majority of DIPG have H3 K27M mutations so your son may be eligible for this, if his tumor is positive for the mutation.

      http://btcocktails.blogspot.is/2017/06/onc201-expand-access-for-h3-k27m-mutant.html

      Delete
  10. Anonymous12 June 2017 at 04:14

    Thanks so much, Stephen — that looks really promising! We're expecting biopsy lab results any day now, which will tell us if it is positive or not.

    As for the extract, after filtering the sludge through muslin cloth and then a coffee filter, I got ~180ml of clear extract.

    ReplyDelete
  11. Semyon24 January 2018 at 09:27

    Here, everyone can buy Withaferin A. (The order must be done through a company with a license. This is not such a big problem.)
    How however can I use Withaferin A in this form ??

    https://www.sigmaaldrich.com/catalog/product/sigma/w4394?lang=en&region=US

    "Biochem/physiol Actions
    Steroidal lactone that exhibits cytotoxicity towards tumor cells. Protective effects attributed to anti-lipid peroxidative, antioxidant and detoxifying functionality.

    Withaferin A is a steroidal lactone that is isolated from the plant Withania somnifera. It has potent anti-inflammatory properties as it inhibits the activation of NF-κ B signaling pathway.[2] The anti-tumor activity of Withaferin A is due to its ability to alter cytoskeletal architecture by binding annexin II and disrupting F actin cross-links.[1] Withaferin A also inhibits angiogenesis by binding to vimentin and F-actin.[3]

    Preparation Note
    Withaferin A yields a clear, colorless solution in methanol at 1 mg/ml.

    Application
    Withaferin A was used to treat HEK293 cells to study its effect on cystic fibrosis inflammation."

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    Replies
    1. Stephen W24 January 2018 at 10:49

      To my knowledge, there has never been a clinical trial using purified withaferin A, so the safety and proper dosing in humans is completely unknown. I would not take risks with this. Some brands of ashwagandha boast *minimal* levels of withaferin A as being a good thing.

      http://nutragenesis.com/sensoril-optimized-ashwagandha-root-and-leaf-nutraceutical-extract-possesses-unsurpassed-efficacy-and-safety/

      To experiment with pure withaferin A is essentially doing a phase 1 chemotherapy trial on oneself with no prior knowledge of safety, toxicity, or proper dose. It could very easily end up doing more harm than good.

      All clinical trials with Withania somnifera (Ashwagandaha) have used whole plant extracts likely containing <1% withaferin A.

      AshwaMax may soon be available from the same company that makes Longvida Curcumin
      http://vs-corp.com/ashwamax/

      According to mouse studies, this product contains 4.3% withaferin A, which is on the high side compared to other Ashwagandha products.

      Delete
  12. Semyon29 January 2018 at 13:12

    3%, 12mg Withaferin A:
    https://www.iherb.com/pr/Life-Extension-Geroprotect-Longevity-A-I-30-Softgels/78403
    + 300mg Gamma-linolenic acid (GLA)

    By the way, what do you say about Gamma-linolenic acid (GLA)?
    I found only this: https://www.ncbi.nlm.nih.gov/pubmed/17599036
    https://pharmaceuticalintelligence.com/2013/07/15/gamma-linolenic-acid-gla-as-a-therapeutic-tool-in-the-management-of-glioblastoma/

    Unfortunately, GLA was injected intravenously or into tumor beds. Probably from this nutritional Supplement (GLA+Withaferin) will not be much use?

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    Replies
    1. Stephen W30 January 2018 at 16:25

      See the brief discussion of GLA in the 2017 Treatment Options, Chapter 7.
      http://virtualtrials.com/pdf2017/treatment_options_gbm_2017.pdf

      My research suggests that Omega 3 fish oils would be much more likely to actually get into the brain following oral administration.


      Delete