Can you optimize your brain and nerve health with antioxidants, certain herbs, and “nootropics?” What does the current research say about brain and nerve boosting herbs and nootropics?
And…what exactly is a “nootropic?”
Brain and nerve nootropics: reduce disease risk and optimize health
Nootropics are compounds, both synthetic and natural, that are believed to improve the function of nerves–as manifested by improvements in memory, creativity, motivation, or attention.
Sound far-fetched? Not so much…
Caffeine is a natural substance we all know, and it is considered a nootropic. Caffeine supports memory, motivation, and attention indirectly–predominantly through its stimulant properties.
The effects found in research are mixed, but there is research to suggest improvements in brain and nerve function from caffeine consumption. These results may be more pronounced in situations involving fatigue, as well as for elders versus younger persons.
Additionally, habitual caffeine intake may slightly reduce the rate of cognitive decline…again, the research is mixed. Perhaps more promising, caffeine appears to protect against the risk of developing Parkinson’s disease.
Caffeine: a powerful nootropic against Parkinson’s disease
While the protective effects of caffeine against general memory loss, along with day-to-day brain-enhancing effects remain debatable, caffeine’s protective effects against Parkinson’s disease specifically appear to be supported by a wealth of research.
For example, a prospective study followed over 8,000 Japanese-Americans for a period of 30-years, evaluating their risk of developing Parkinson’s disease by age 65. Those that drank approximately 784mg/ kg of coffee per day had a 5-fold lower risk of developing Parkinson’s disease.
Similar results were repeatedly demonstrated in much larger studies, including a systematic review of 120 observational studies, a meta-analysis of 13 studies involving over 900,000 participants (26% Parkinson’s disease risk reduction for every 200mg of caffeine per day, max effects at 3 cups of coffee), as well as the Health Professionals’ Follow-Up Study and the Nurses’ Health Study–which combined involved approximately 130,000 individuals.
The optimal dose based on all these studies? The research repeatedly suggests around 3 cups of coffee daily on average (approximately 300 mg of caffeine) for maximal effects.
Hate coffee? Drink tea.
So, is it the caffeine, or the coffee? The protective benefits appear to be linked to specifically the caffeine, as decaffeinated coffee did not offer the same risk reduction according to the research trials.
Caffeine appears to work its magic in protecting nerve cells by binding with adenosine A2A receptors. In blocking these receptors, caffeine appears to protect neurons against toxins, reduce nerve cell destruction, reduce nerve cell inflammation, and protects against over-stimulation (excitotoxicity) of these nerve-cell receptors.
Interesting enough, in animal research (which allows for more direct observation of effects of caffeine on brain cells), caffeine protected nerve cells from progressive damage after exposure to a known neuro-toxin—even when caffeine was administered 2-weeks after the toxin exposure.
Caffeine also has research-backed support for its ability to reduce the symptom severity of mood and cognitive disorders that occur with Parkinson’s disease. Recently, the FDA approved a drug as an add-on therapy (in addition to levodopa) for Parkinson’s patients that works similar to caffeine in binding to the same receptors.
So, the research is clear, natural substances can be found in the plant-world that protect our nerves against various diseases. Nootropics are a “thing,” and a number of plant-substances in addition to caffeine are being researched for their potential nerve-cell protecting/ enhancing effects.
Brain and nerve nootropics: how do they work?
Nootropic substances appear to protect brain and nerve health through a variety of functions. These include:
- Reduction of inflammation
- Enhancing activity of enzymes found within brain and nerve cells
- Antioxidant activity
- Prevention of nerve cell destruction (apoptosis)
- Protection of nerve cells against stressors and toxins
The role of nootropics, antioxidants, and plant-based diets
In the post, Your Brain and Nerve Health: Wired For Success!, I explored the impact of diet and nutrition on brain and nerve function.
If you do anything for your brain and nerve health, shifting to a plant-based diet is arguably one of the most important steps–as I demonstrated with powerful and current research findings. To throw a couple supplements on top of a diet rich in eggs, meat, and dairy will likely do little to address the underlying chronic inflammation that results from heavy intake of these pro-inflammatory foods.
However, assuming you are already eating a diet with minimal to no animal products, evaluating antioxidant-rich/ antioxidant-stimulating herbs and supplements for their potential to positively influence your brain and nerve health may be worth a closer look. In this post and upcoming posts, I look at the research on various herbs and nootropics that are touted for nerve- and brain-enhancing properties.
Oxidative stress, antioxidants, and nerve cell aging
Along with chronic inflammation, the role of antioxidants and oxidative stress have been the subject of research exploring why and how our brain and nerve cells decline in function.
Researchers note that the brain begins to shrink in weight and volume by about 5% on average each decade, starting in our 40’s. However, reductions in processing speed and cognitive function can be seen starting as early as our mid-20’s!!
Changes in nerve-cell health, such as destruction of connections, decreased ability for the cells to process metabolic waste products, and loss of supportive structures–such as capillary blood-vessel supply can be attributed in part to oxidative stress. Studies on aging note a decline in our body’s ability to counter oxidant stress with our own internal antioxidant defense-systems as we age.
This leads to increases in oxidative stress, damage to cell structures, and the oxidation/ damage/ and destruction of fats that make up the cell membranes and nerve linings (myelin sheaths responsible for rapid conduction of nerve signals).
Studies link oxidative stress to declines in brain and nerve health
Indeed, higher oxidative stress and lower natural antioxidant levels during a 4-year study period predicted faster rates of cognitive decline. This was the findings in a study of 511 healthy university staff. The measurements of oxidative stress loads included circulating aminothiols (reactive molecules), and the antioxidant measures included glutathione (a strong antioxidant found in human tissues).
The faster glutathione levels fell, the faster cognition also declined. Brain functions most vulnerable included memory, flexible thinking/ adaptability, and ability to control impulses.
Oxidative stress underlies damage to peripheral nerves as well. Similar to the declines in brain function noted when our internal antioxidant levels decrease, peripheral nerve function (nerves located outside the brain) also worsen when internal antioxidant levels decline.
Isolated antioxidant/ nutrient supplementation, such as supplementing with individual vitamins (and possibly omega 3 fatty acids), in absence of a deficiency, appear to have limited value. Excess vitamin E supplementation can even raise the risk of hemorrhagic stroke. However, particular foods and herbs–containing thousands of complex compounds–can be powerful in protecting our brain and nerve health according to research.
Brain and nerve nootropics: herbs
As I demonstrated in my post “Your Brain and Nerve Health: Wired For Success!,” compounds found in minimally processed, whole-food plant-based diets and herbs can have powerful anti-inflammatory and antioxidant neuro-protective effects. One of those research-backed herbs reviewed in that post included sage. Another herb discussed included turmeric.
Sage and turmeric are not the only specific herbs to show promise in terms of promoting healthy nerve function. Additional natural herbs/ nootropics currently being researched using human trials for potential neuro-protective/ enhancing effects include:
- Ginkgo biloba
- Panax ginseng (Korean, Asian, or Chinese ginseng)
- L-theanine (an amino acid found in the leaves of green tea)
- Lion’s mane mushrooms (Hericium erinaceus): please see my post “The Magic of Mushrooms! Current Evidence” for information on the brain and nerve health boosting effects of this amazing mushroom!
- Mucuna pruriens (velvet bean)
Numerous plants found in the mint family (Lamiaceae)—in addition to sage–have research-backed nootropic effects:
- Melissa (Lemon balm)
- Rosmarinus (rosemary)
- Mentha spicata (spearmint)
- Mentha piperita (peppermint)
- Ocimum tenuiflorum, Ocimum sanctum, Ocimum gratissimum (Tulsi or Holy Basil)
The herbs listed above have some fascinating research supporting their use in protecting and enhancing brain and nerve health. When taken in addition to a healthy lifestyle, these herbs and nootropics offer a lot of promise based on current research findings!
A few of the above nootropics are reviewed below, with the others to be reviewed in future posts.
The mint family: a powerful—and tasty–herb family!
The mint family has some powerhouse fascinating herbs. One of my favorites is tulsi, otherwise known as holy basil. Tulsi is native to India and has been a part of Ayurvedic medicine for over 3,000 years! Tulsi has been referred to as “the elixir of life.”
Brain and nerve nootropic: tulsi (Holy Basil)
Research-backed benefits of tulsi include:
- Antioxidant source: cellular protection against toxins due to a being a rich source of polyphenols and other plant-based antioxidants
- Augmentation of our own internal antioxidant activity: tulsi stimulates our bodies to enhance our own internal antioxidant supply of glutathione, superoxide dismutase, and catalase—major body defenses against free radical damage that can occur within our cells
- Enhancement of liver detox-enzyme activity (cytochrome P450 enzyme activity)
- Organ (brain, kidney, liver) protection and DNA protection against toxin-induced damage caused by a variety of metals, industrial chemicals, and pesticides
- Reductions in damage from radiation through free radical scavenging activity
- Anti-cancer effects through stimulation of apoptosis (cell-suicide) in precancerous and cancerous cells
- Reduction in dementia symptoms along with boosted neurotransmitter activity in human studies and animal models
Tulsi and human research trials
A systematic review of multiple research trials concerning tulsi’s effects on humans selected 24 human study trials. Many of these studies utilized double-blinded and randomized-controlled study designs, with the systematic review involving over 1,000 participants in total. Health benefits identified in the various human trials found the following benefits of tulsi:
- Anti-diabetic effects: multiple studies on diabetics showed significant glucose lowering effects, with some diabetics achieving near normal blood sugar levels. Improvements impacted fasting glucose, glucose following meals, and improved HgA1C levels
- Weight loss
- Blood pressure reduction according to multiple human trials, with one study finding a 25% reduction in blood pressure levels
- Improvements in cholesterol profiles and reductions in triglyceride levels
- Anti-gout effects: significant reductions in uric acid levels in persons suffering from gouty arthritis. Elevated levels of uric acid contribute to heart disease, chronic inflammation, and damage to joints.
- Improved physical performance and reductions in fatigue, as well as reductions in muscle damage markers including creatine kinase (CK) and lactic acid levels versus a placebo control group
- Immune-system modifying effects: significant increases in cytokine levels of interferon-ϒ (a stimulant of natural killer cells, with antiviral effects, among other cell mediated immune stimulating effects), increases in interleukin-4–a powerful anti-inflammatory cytokine, and boosted levels of T-helper cells
- Reductions in asthma symptoms
- Reductions in symptoms due to viral hepatitis
- Improved survival rates in patients with viral encephalitis (infection and inflammation of the brain) versus standardized medical treatment with steroids
- Improved brain/ cognition performance: improved working memory, attention, and flexibility (ability to manage multiple tasks at once)
- Anti-stress: reductions in stress symptoms by 31.6%–39%, including reductions in fatigue, sleep disruptions, sexual problems, and anxiety levels
- Anti-aging: significant improvements in biological age score
- Safety: in all 24 studies, only one reported presence of sides effects, with that side effect being mild nausea
Tulsi is pretty impressive due to its effects of stimulating internal mechanisms within our bodies–boosted liver enzyme activity, boosted internal antioxidant activity, and increased immune-system activity.
As such, the total effects of tulsi go beyond simply the number of antioxidants obtained from the plant itself. Stimulation of internal mechanisms are likely responsible for the significant clinical effects, including those effects that promote brain and nerve health.
Brain and nerve nootropics: Lemon Balm
Native to southern Europe and the Mediterranean, lemon balm has been used in traditional medicine for anti-anxiety, memory-enhancing, anti-bacterial, blood-pressure lowering, and anti-spasmatic effects in numerous cultures across the globe. Included in the FDA Generally Recognized as Safe (GRAS) list (except possibly during times of pregnancy), lemon balm offers a number of benefits with minimal downsides.
Rich in bioactive flavonoids, tannins, polyphenols, rosmarinic acid, caffeic acids, and numerous other compounds, researched-backed benefits of lemon balm include:
- Antiviral activity including anti-replication activity against influenza and herpes viruses–even achieving a B-level evidence rating suggesting good scientific evidence for treatment of herpes
- Antibacterial/ anti-fungal activity against a variety of yeasts and bacteria species
- Anti-inflammation effects
- Antianxiety activity with binding activity at gamma-aminobutyric acid A (GABAA) receptors (the same receptors bound by anti-anxiety medications)
- Anticancer activity against a variety of human cancer cell-lines (lab setting)
- Anti-oxidant effects
Lemon balm and human research trials
Human research trials studying the effects of lemon balm include double-blinded randomized-controlled trials (considered gold-standard for studying the effects of an intervention), clinical trials, and randomized cross-over designed studies. Study-group size tends to be small in these studies. Nonetheless, results are promising with the following findings:
- Calming effects for people with dementia: Lemon balm essential oil reduced agitation in dementia patients versus a placebo lotion as measured by the Cohen-Mansfield Agitation Inventory (CMAI) in a double-blinded, placebo-controlled trial of 79 patients with dementia.
- Reduced anxiety symptoms when ingesting lemon balm in a variety of trials including double-blinded, randomized placebo-controlled trials, with significant improvements noted in ability to concentrate, reductions in feelings of agitation and weakness, reductions in sleeplessness and fatigue.
- Significantly improved cognitive function in numerous controlled research trials, including double-blinded randomized trials. These findings included healthy participants and patients with dementia. Improvements included increased working memory, attention, and performance on a variety of cognitive performance test scores
- Improved sleep quality when combined with valerian root, as demonstrated by number of randomized-controlled studies. Improvements included increased sleep length, decreased awakenings, and improvements in stage 3 and 4 deep sleep.
Other mint family members: rosemary, spearmint, and peppermint
Other members of the mint family researched for brain, nerve, and general health benefits include rosemary, spearmint, and peppermint. The research trials around some of these mint family members are less robust in terms of study design and size when compared to the research on tulsi and lemon balm.
Still, compounds found in plants in the mint family appear to positively impact brain and nerve function by impacting neuro-transmitter and enzyme activities. Such activities include GABAA, nicotinic and NMDA receptor binding properties, as well as acetylcholinesterase (AChE) inhibition.
Brain and nerve nootropics: Spearmint
A controlled study on spearmint ingestion for people ages 50-70 found improvements in working memory, vigor, mood, sleep onset, and alertness after 90 days ingesting 600 mg and 900 mg of an aqueous extract of spearmint that contained the phenolic constituents.
Brain and nerve nootropics: Peppermint
A separate, small, controlled trial similarly found that peppermint oil ingestion significantly improved cognitive performance on a variety of cognitive tests measuring accuracy, recall, speed, among other measures. Participants in the group ingesting the peppermint oil also experienced reduced fatigue versus those in placebo group when tests were conducted at 1 hour, 3 hours, and 6 hours post-ingestion.
Interestingly, neurons in a cell culture (lab setting) exposed to a nerve toxin experienced modestly reduced damage when bathed in peppermint oils versus control groups.
Brain and nerve nootropics: Rosemary
Native to the Mediterranean and sub-Himalayan regions, rosemary is stirring interest in the research community due to its therapeutic potential for a number of conditions. Bioactive compounds found in rosemary include triterpenes, phenols, and phenolic acids including rosmarinic acid, carnosic acid, rosmanol, carnosol, ursolic acid and betulinic acid.
Rosemary is included in the FDA’s Generally Rocognized as Safe List. The compounds found in rosemary have been noted by research studies to possess the following benefits:
- Pain soothing effects
- Nerve cell protecting
- Calming effect
- Mood enhancing effects
Rosemary research trials
Animal studies (which are preliminary/ do not always translate to results in humans) show acetylcholinesterase (AChE) inhibition, leading to greater availability of acetylcholine (a neurotransmitter) in the brain. This effect led to reduction of depression/ low activity symptoms in animal models along with reductions in hyperactivity symptoms.
Memory and recall were also boosted in animal models. Similar to tulsi, animal studies of rosemary found boosted levels of internal antioxidants and inhibition of inflammatory cytokines.
Animal studies also affirmed rosemary’s protective effects against nerve cell damage due to free radicals (oxidants). Rosemary appears to inhibit T-type calcium channels (TTCCs) in the brain, protecting nerve cells from excessive stimulation. Such effects may protect nerve cell integrity plus reduce the risk for seizures.
Dopamine generating nerve cells bathed in rosemary compounds (carnosic acid) were protected against a toxin challenge in a lab dish study, and animal studies using nerve toxins also demonstrated rosemary’s ability to protect animals against Parkinson’s onset following toxin exposure.
Rosemary human research trials
Small human trials noted consumption of rosemary powder improved speed of memory recall for working memory and memory of every day events (episodic memory). Rosemary aromatherapy reduced cortisol levels and boosted mood and performance on cognitive tests.
In a 4-week human trial with 81 patients being treated for opioid-addiction, consumption of rosemary capsules containing 300mg of dried rosemary leaves each were noted to reduce pain, reduce insomnia symptoms, and reduce muscle jerks, easing withdrawal symptoms.
Brain and nerve nootropics: in summary
In my first post on the subject of brain and nerve health, I covered the research findings demonstrating the harms of chronic inflammation—much of which can be attributed to diets high in animal-based products. Toxic stresses to our nerves include even mild elevations in blood sugar, vascular disease, excessive uric acid levels, toxins, and oxidative damage (among other factors).
Antioxidants, herbs, and nootropics are research-backed regarding their ability to promote brain and nerve health by countering many of these insults. The effects are not to be dismissed as trivial.
Significant reductions in the risk of developing Parkinson’s disease, reductions in the harmful effects of diabetes, improvements in healing sleep, shielding from toxins prevalent in our environment, improvements in neuro-processing speeds and cognition—the potential nootropic herbs and substances have to enhance our day-to-day life is significant!!!!
This post covered the effects of caffeine and herbs from the mint family on our brain, nerve, and general health. Future posts will explore some of the other nootropics described above. Live well!!!
Cohen M. M. (2014). Tulsi – Ocimum sanctum: A herb for all reasons. Journal of Ayurveda and integrative medicine, 5(4), 251–259. https://doi.org/10.4103/0975-9476.146554
Ghasemzadeh Rahbardar, M., & Hosseinzadeh, H. (2020). Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders. Iranian journal of basic medical sciences, 23(9), 1100–1112. https://doi.org/10.22038/ijbms.2020.45269.10541
Giridharan, V. V., Thandavarayan, R. A., Mani, V., Ashok Dundapa, T., Watanabe, K., & Konishi, T. (2011). Ocimum sanctum Linn. leaf extracts inhibit acetylcholinesterase and improve cognition in rats with experimentally induced dementia. Journal of medicinal food, 14(9), 912–919. https://doi.org/10.1089/jmf.2010.1516
Hajjar, I., Hayek, S.S., Goldstein, F.C. et al. Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study. J Neuroinflammation 15, 17 (2018). https://doi.org/10.1186/s12974-017-1026-z
Hammi C, Yeung B. Neuropathy. [Updated 2020 Nov 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542220/
Harvard Health Publishing. (2021). Don’t buy into brain health supplements. Retrieved from https://www.health.harvard.edu/mind-and-mood/dont-buy-into-brain-health-supplements
Jamshidi, N., & Cohen, M. M. (2017). The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the Literature. Evidence-based complementary and alternative medicine : eCAM, 2017, 9217567. https://doi.org/10.1155/2017/9217567
Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biological psychology, 74(1), 39–45. https://doi.org/10.1016/j.biopsycho.2006.06.006
Lampariello, L. R., Cortelazzo, A., Guerranti, R., Sticozzi, C., & Valacchi, G. (2012). The Magic Velvet Bean of Mucuna pruriens. Journal of traditional and complementary medicine, 2(4), 331–339. https://doi.org/10.1016/s2225-4110(16)30119-5
Lopresti A. L. (2017). Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects. Drugs in R&D, 17(1), 53–64. https://doi.org/10.1007/s40268-016-0157-5
Mallet, ML., Hadjivassiliou, M., Sarrigiannis, P.G. et al. The Role of Oxidative Stress in Peripheral Neuropathy. J Mol Neurosci 70, 1009–1017 (2020). https://link.springer.com/article/10.1007%2Fs12031-020-01495-x#citeas
The Mayo Clinic. (2021). Caffeine content for coffee, tea, soda and more. Retrieved from https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/caffeine/art-20049372
Mori, K., Inatomi, S., Ouchi, K., Azumi, Y., & Tuchida, T. (2009). Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytotherapy research : PTR, 23(3), 367–372. https://doi.org/10.1002/ptr.2634
Nehlig A. (2010). Is caffeine a cognitive enhancer?. Journal of Alzheimer’s disease : JAD, 20 Suppl 1, S85–S94. https://content.iospress.com/articles/journal-of-alzheimers-disease/jad091315
Onaolapo, A. Y., Obelawo, A. Y., & Onaolapo, O. J. (2019). Brain Ageing, Cognition and Diet: A Review of the Emerging Roles of Food-Based Nootropics in Mitigating Age-related Memory Decline. Current aging science, 12(1), 2–14. https://doi.org/10.2174/1874609812666190311160754
Qi, H., & Li, S. (2014). Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease. Geriatrics & gerontology international, 14(2), 430–439. https://doi.org/10.1111/ggi.12123
Ren, X., & Chen, J. F. (2020). Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms. Frontiers in neuroscience, 14, 602697. https://doi.org/10.3389/fnins.2020.602697
Ross, G.W., Petrovitch, H. Current Evidence for Neuroprotective Effects of Nicotine and Caffeine Against Parkinson’s Disease. Drugs Aging 18, 797–806 (2001). https://doi.org/10.2165/00002512-200118110-00001
Singh, N., Bhalla, M., de Jager, P., & Gilca, M. (2011). An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. African journal of traditional, complementary, and alternative medicines : AJTCAM, 8(5 Suppl), 208–213. https://doi.org/10.4314/ajtcam.v8i5S.9
Ulbricht, C., Brendler, T., Gruenwald, J., Kligler, B., Keifer, D., Abrams, T. R., Woods, J., Boon, H., Kirkwood, C. D., Hackman, D. A., Basch, E., Lafferty, H. J., & Natural Standard Research Collaboration (2005). Lemon balm (Melissa officinalis L.): an evidence-based systematic review by the Natural Standard Research Collaboration. Journal of herbal pharmacotherapy, 5(4), 71–114. Retrieved from https://www.researchgate.net/publication/7144806_Lemon_balm_Melissa_officinalis_L_an_evidence-based_systematic_review_by_the_Natural_Standard_Research_Collaboration
Zhang, J. M., & An, J. (2007). Cytokines, inflammation, and pain. International anesthesiology clinics, 45(2), 27–37. https://doi.org/10.1097/AIA.0b013e318034194e