Ashwagandha in Cancer Care: Promise, Evidence, and Precautions

Ashwagandha (Withania somnifera) is a traditional medicinal herb used for more than 3,000 years in Ayurvedic medicine. It is classified as an adaptogen, meaning it helps the body adapt to physical and psychological stress while promoting restoration of physiologic balance. The primary bioactive compounds are withanolides, steroidal lactones that possess anti-inflammatory, antioxidant, neuroprotective, immunomodulatory, and anxiolytic properties. (1) The roots of the plant are considered the most important part of the whole plant, as they are rich in bioactive molecules, especially withanolides, which are responsible for their medicinal property. (2) Ashwagandha has been used for centuries to treat many chronic diseases like high blood pressure, arthritis, diabetes, Alzheimer’s disease, and depression. Ashwagandha has been shown to play a significant role in immunological diseases by modulating several cytokines, increasing T-cell proliferation, and enhancing macrophage function.

Ashwagandha as an Anxiolytic

Among herbal medicines, ashwagandha has some of the strongest clinical evidence for reducing anxiety.

Its anxiolytic effects appear to result from several complementary mechanisms:

• Reduces cortisol production by modulating the hypothalamic-pituitary-adrenal (HPA) axis.

• Enhances GABAergic neurotransmission, producing calming effects similar to (but much milder than) benzodiazepines without causing significant sedation.

• Reduces sympathetic nervous system activity, lowering the “fight-or-flight” response.

• Decreases neuroinflammation and oxidative stress, both increasingly recognized contributors to anxiety disorders.

• Improves sleep quality, which further reduces anxiety symptoms.

Clinical Evidence

Randomized controlled trials have shown a significant benefit in terms of stress reduction, improved cognition and mood (reduction of depression) and quality of sleep. (3-5) In a double-blind, placebo-controlled randomized controlled trial, participants who had chronic stress were randomized to ashwagandha extract (300 mg twice daily) or placebo for 60 days. (6) At the end of 60 days, participants in the active treatment group had a 44% (p< 0.001) reduction in stress scores and a 28% (p< 0.001) reduction in cortisol levels.

Similarly, Remenapp et al reported that one month of Ashwagandha supplementation had a positive effect on the participants’ cortisol levels, cognitive ability, and self-reported stress, anxiety, depression, and food cravings, and was devoid of serious adverse events. (7) A randomized-placebo controlled trial demonstrated that Ashwagandha improved cognitive function (auditory-verbal working memory and social cognition) in patients with bipolar disorder. (8)

Across meta-analyses: (9-11)

• 20–40% reductions in validated anxiety scores are commonly reported.

• Significant reductions in serum cortisol (typically 15–30%)

• Improved sleep quality

• Improved overall quality of life

• Reduced fatigue

Role in Integrative Oncology

Ashwagandha is increasingly being studied as an adjunct in cancer care because it may provide benefits beyond anxiety reduction. Experimental and early clinical studies suggest it may:

• Reduce chemotherapy-related fatigue

• Improve sleep and quality of life

• Lower chronic stress hormones (cortisol)

• Reduce systemic inflammation

• Protect normal tissues from oxidative stress

• Potentially enhance immune function

Preclinical studies have demonstrated the ability of this plant to regulate mitochondrial function and apoptosis and reduce inflammation by inhibiting inflammatory markers such as cytokines (including IL-6 and TNF-a), nitric oxide, and reactive oxygen species. Ashwagandha plays a major role in the induction of cancer cell apoptosis, it inhibits cell proliferation and inhibits cell migration. (12-14) In glioblastoma cells ashwagandha triggers cell cycle arrest and apoptosis. (15) In a human head and neck cell line ashwagandha showed dose-dependent growth-inhibitory activity attributed to caspase-dependent apoptosis. (16) Loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase 9 suggested that ashwagandha leads to activation of mitochondria-mediated apoptosis.

Widodo et al demonstrated the cancer killing activity of ashwagandha mediated by p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling and that the selective killing of cancer cells was mediated by induction of oxidative stress. (17) The anti-cancer effects of ashwagandha on the proliferation and migration of colorectal cell lines has been shown to be due to reduced transcriptional activity of STAT3. (18) In addition, Notch 1 and Notch/AKT/mTOR signaling is inhibited by ashwagandha in a colon cell line. (19) In an experimental adenomatous polyposis coli model ashwagandha was associated with a 59% reduction of tumor and polyp initiation and progression. (20)

Ashwagandha has potent anti-inflammatory activity that likely has a major effect on the tumor microenvironment inhibiting angiogenesis and metastasis. In a study using the HaCaT human keratinocyte cell line, an aqueous solution from Ashwagandha root was found to inhibit the NF-ƘB and MAPK (mitogen-activated protein kinase) pathways by decreasing the expression of proinflammatory cytokines, including interleukin (IL)-8, IL-6, tumor necrosis factor (TNF-α), IL-1β, and IL-12, and increasing the expression of anti-inflammatory cytokines. (21)

In an vivo and in vitro model, Jawarneh et al. demonstrated that a combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin. (14) The combination was found to decrease cancer cell proliferation through apoptosis induction, while also reducing cisplatin-induced toxicity in the liver and kidney.

Clinical studies

In the setting of cancer, Ashwagandha has been studied almost exclusively in experimental models, with limited clinical data regarding its clinical efficacy. Biswell et al performed an open-label prospective non-randomized comparative trial on 100 patients with breast cancer to receive either a combination of chemotherapy with Ashwagandha or chemotherapy alone.(22) Withania somnifera root extract was administered to patients in the study group at a dose of 2 g every 8 hours, throughout the course of chemotherapy. Patients in the treatment group had significantly less fatigue and higher quality of life scores. The 24-month overall survival for all stages in study and control group patients were 72% versus 56%, respectively; however, the result was not significant.

As discussed under the section of stress reduction and sleep, Ashwagandha has proven to be a safe and effective adaptogen. RCTs have shown a significant benefit in terms of stress reduction, improved cognition and mood, and quality of sleep. (3-5) A meta-analysis of 12 RCTs demonstrated that ashwagandha supplementation significantly reduced anxiety (p = .005) and stress levels (p = .005) compared to placebo. (11) While ashwagandha has not been proven to improve the outcome of patients with cancer, because of its effects on stress reduction, sleep, and quality of life we have included this herb as a recommend therapy in patients with cancer.

Typical Dose

Most clinical studies have used standardized root extracts:

• 300 mg twice daily (most common)

• 500–600 mg once daily

Benefits generally begin after 2–4 weeks, with maximal benefit by 6–8 weeks.

Safety

Ashwagandha is generally well tolerated.

Possible adverse effects include:

• Mild gastrointestinal upset

• Sleepiness in sensitive individuals

• Rare allergic reactions

Because it may stimulate thyroid hormone production, caution is advised in patients with hyperthyroidism or those taking thyroid replacement therapy. It should also be used cautiously with sedatives or immunosuppressive medications.

Ashwagandha does not appear to be a phytoestrogen

Unlike soy (genistein), flax (lignans), or red clover (isoflavones), ashwagandha does not contain compounds known to bind estrogen receptors (ERα or ERβ) with meaningful affinity. There is currently no convincing evidence that ashwagandha stimulates estrogen receptor-positive breast cancer.

Ashwagandha a testoterone booster

Ashwagandha has been widely promoted as a “natural testosterone booster,” but the clinical evidence is more nuanced. Overall, it appears to increase testosterone modestly in some men, particularly those with infertility, chronic stress, obesity, or low-normal testosterone levels. In contrast, healthy young men with normal testosterone generally experience little or no increase.

Men with chronic stress

Randomized trials consistently demonstrate:(3, 23)

• Lower cortisol (15–30%)

• Improved energy

• Improved sexual well-being

• Small increases in testosterone

The testosterone increase is believed to be secondary to cortisol reduction.

Meta-analyses

Recent systematic reviews conclude:(24, 25)

• Small but statistically significant increases in testosterone in men

• Greatest benefit occurs in:

  • Men with infertility

  • Men under significant stress

  • Men with lower baseline testosterone

• Minimal effect in healthy eugonadal men

The average increase is approximately:

• 40–80 ng/dL in total testosterone

This is considerably smaller than testosterone replacement therapy but may be clinically meaningful in selected individuals.

Prostate Cancer

The use of ashwagandha in men with prostate cancer is controversial. Because prostate cancer can be driven by androgens, any supplement that may increase testosterone is usually avoided or used only under close medical supervision. Memorial Sloan Kettering’s integrative medicine reference explicitly advises that ashwagandha should be avoided in patients with hormone-sensitive prostate cancer, and other oncology sources echo the same caution. The Merck Manual states that ashwagandha may increase testosterone levels and “may have a negative impact on prostate cancer,” and therefore should be avoided in people for whom this is a concern.

Practical Bottom Line

For patients with anxiety—particularly those experiencing chronic stress, insomnia, or cancer-related distress—ashwagandha is one of the best-studied herbal anxiolytics available. A standardized extract at 300 mg twice daily has demonstrated consistent reductions in anxiety and cortisol with a favorable safety profile. In the context of the metabolic approach to cancer, its primary role is supportive: reducing stress, improving sleep, and potentially lowering neuroendocrine signals that may contribute to tumor progression, rather than acting as a primary anticancer therapy.

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Medical Disclaimer: The discussion of repurposed medications and nutraceuticals in this article is intended to review the scientific literature and does not constitute a recommendation for self-treatment. Decisions regarding the use of off-label therapies should be made in consultation with a qualified healthcare professional familiar with the patient’s medical history and current treatment plan. Please see the full Medical Disclaimer on the introductory page to Marik’s Cancer & Metabolic Healing Playbook.

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