by Ari Magill, MD
Benefits to Nerves of Lab Rodents
Connection between neurons results from outgrowths of them, called dendrites (the receiving apparatus) and axons (the sending apparatus). The site where chemical messengers are transmitted from the terminal end of the axon to the dendrite is called the synapse. Administration of ASH extract placed in drinking water increased the density of axons, dendrites, and synapses in neuronal tissue taken from the rat cortex (the outer layer of the brain). It also functionally improved the spatial memory of mice in a water maze test after injecting their brains with beta amyloid.
Mouse Memory Boosted
Amyloid Clearance Improved
Other animal studies suggest a cognitive benefit from oral ASH administration. Shivamurthy et al investigated the impact of protein extracts of the herb on the memory function of albino rats (those that don’t produce pigmentation).6 Researchers assessed the rats’ recall ability using a water maze and avoidance learning tasks. They were co-administered scopolamine (an anti-cholinergic medication that blocks the activity of acetylcholine). Acetylcholine is a key neurotransmitter (brain chemical messenger) involved in memory formation.a
The investigators found that the ASH protein extract improved learning and memory performance compared to rats treated with scopolamine alone and rats treated with a combination of scopolamine and piracetam.b
In an attempt to clarify the exact mechanism by which ASH extracts reverse scopolamine-induced memory loss in mice, Konar et al investigated the molecular target of an ASH extract using an albino mouse model.7 They focused on a particular acetylcholine receptor, M1 muscarinic, which induces cellular changes that enhance learning and memory. After giving mice the ASH extract by mouth for a week, they examined two regions of the brain—the cerebral cortex and the hippocampus (the brain’s memory center). They also harvested hippocampal cells from neonatal mice and directly applied the ASH extract.
They found that it promoted the formation and growth of neuronal dendrites and blunted the negative effects on these processes by scopolamine. A known muscarinic receptor blocker, dicyclomine, prevented growth and generation of dendrites by the ASH extract, and pilocarpine, a known muscarinic receptor activator, enhanced the effects of the extract. Thus, ASH does appear to exert its cognitive enhancing effects, at least in part, through the acetylcholine M1 muscarinic receptor.
Studies in Humans
Administration resulted in significant increases in processing speed performing all the cognitive tasks except finger tapping. This study suggests that ASH extracts have cognitive enhancing properties in healthy young adults.
Choudhary et al conducted a pilot study in which 50 subjects with mild cognitive impairment were enrolled.9 Participants received either 300 mg of an ASH extract twice daily or placebo for eight weeks. Cognitive testing revealed that those given the extract had significantly better cognitive scores in multiple domains including memory, executive function (decision making), persistent attention, and information processing speed compared to the placebo group.
Overall, results are preliminary but there is a scientific basis for thinking that ASH might have cognitive protective effects through antioxidant, cholinergic (acting through the acetylcholine messenger system), and other mechanisms of action. The herb is generally considered quite safe, and side effects are rare, but GI symptoms, including dyspepsia, diarrhea, nausea, and vomiting have been documented at higher doses.10 ASH root extracts are readily available in health food stores and online without a prescription. No consistent dosage has been established, but human studies have used doses in the 600-mg to 1000-mg (per day) range. Sprouts sells a bottle of 90 475-mg capsules (containing whole root and an extract) for $17. A 1-ounce liquid formulation sells for $12 and can be used to gradually titrate up the dose if side effects occur.
b Piracetam is another agent frequently taken to enhance cognitive performance.
- Farooqui AA, et al. Ayurvedic medicine for the treatment of dementia: mechanistic aspects. Evid-Based Complement Alternat Med. 2018;2481076. doi: 10.1155/2018/2481076.
- Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144(7):961-971. doi: 1038/sj.bjp.0706122.
- Kuboyama T, Tohda C, Komatsu K. Withanoside IV and its active metabolite, sominone, attenuate Aβ (25–35)‐induced neurodegeneration. Eur J Neurosci. 2006;23(6):1417-1426. doi: 1111/j.1460-9568.2006.04664.x.
- Sehgal N, et al. Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc Natl Acad Sci. 2012;109(9):3510-3515. doi: 1073/pnas.1112209109.
- Shah N, et al. Combinations of ASH leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. PLoS One. 2015;10(3):e0120554. doi: 10.1371/journal.pone.0120554.
- Shivamurthy S, Manchukonda RS, Ramadas D. Evaluation of learning and memory enhancing activities of protein extract of Withania somnifera (ASH) in Wistar albino rats. Int J Basic Clin Pharmacol. 2016;5(2):453. doi: http://dx.doi.org/10.18203/2319-2003.
- Konar A, et al. M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration and memory recovery by i-Extract from Withania somnifera. Sci Rep. 2019;9(1):1-15. doi: 1038/s41598-019-48238-6.
- Pingali U, Pilli R, Fatima N. Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants. Pharmacognosy Res. 2014;6(1):12-18. doi: 4103/0974-8490.122912.
- Choudhary D, Bhattacharyya S, Bose S. Efficacy and safety of Ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions. J Diet Suppl. 2017;14(6):599-612. doi: 10.1080/19390211.2017.1284970.
- National Institutes of Health. Livertox: clinical and research information on drug-induced liver injury. National Institutes of Health website. https://livertox.nih.gov.