For millenia, humans have sought to enhance creativity, stimulate motivation and improve brain function. Herbs such as Bacopa monnieri, tulsi and gotu kola (known as “the student herb” in ancient Balinese culture) have been used for thousands of years in Eastern medicine.
Eaten raw or dried, pulverized and used in teas, they were traditionally ingested to increase attentional control, working memory and cognitive flexibility, as well as improve so-called “executive functions” such as planning, reasoning and problem solving.
Coined from the Greek words nóos (mind) and trop, meaning “a turning,” the word nootropic was first used by Corneliu Giurgea, a Romanian psychologist and chemist, in 1972 to describe a class of molecules that selectively acted to improve brain function.
To qualify as a genuine nootropic, Giurgea insisted that a substance meet five criteria: 1) improve working memory and learning, 2) support brain function under hypoxic (low oxygen) conditions or after electroconvulsive therapy, 3) protect the brain from toxicity, 4) enhance cognitive functions and 5) be nontoxic to humans (including not causing side-effects like depression or overstimulation of the brain).
Today, prompted by movies such as Lucy (2014) and Limitless (2011) and the 2015 television series of the same name—all of which feature a main character granted fantastic mental capabilities through ingesting an illegal drug—nootropics are in hot demand. Now a billion-dollar industry, up to 70 percent of college students are estimated to take nootropic substances at exam time.1
Both students and adults in the workforce cite achieving a competitive advantage at school or work and coping with social pressure to succeed as the main reasons for using nootropics, hoping to maintain high levels of attention while improving their flagging motivation to handle tasks (and jobs) that are difficult or unappealing.
Better known as “smart pills” or “smart drugs,” nootropics—which have mostly been studied for their effects on dementia, Alzheimer’s and traumatic brain injury—affect brain performance through a number of mechanisms.
They can act as a vasodilator of small arteries and veins in the brain, increasing the flow of nutrients to the brain, and they can also positively affect the dopaminergic and cholinergic systems, the neurons that produce the “feel good” neurotransmitter dopamine and the essential neurotransmitter acetylcholine (ACh), which plays a role in memory, thinking, and learning.2
Nootropics can be found in three forms:
1) dietary supplements such as vitamins and minerals, herbs and botanicals, amino acids, enzymes and other diet components including foods;
2) synthetic compounds made in laboratories such as racetams (a class of drugs that stimulate glutamate receptors in the brain), modafinil (a prescribed drug for narcolepsy), methylphenidate (the active substance in Ritalin), and vinpocetine (a synthetic drug that mimics a substance found in the periwinkle plant to increase brain metabolism);
3) prescription drugs such as piracetam (commonly prescribed for seizures and movement disorders) and donepezil (a drug given to Alzheimer’s patients that affects the neurotransmitter acetylcholine in the brain). Synthetics and prescription drugs often overlap.
Studies that have been done on nootropics taken by healthy people primarily focus on synthetic and prescription drugs, and results are less than inspiring.
On the other hand, natural nootropics like Ginkgo biloba, Panax quinquefolius (American ginseng) and dozens of other herbs, enzymes, amino acids and foods have been shown to boost brain function while making the brain healthier.
“Taking the natural approach, we can boost the nutrients that are deficient in the body in people with Alzheimer’s and dementia,” says Michael Edson, MA, LAc, and the author of Natural Brain Support (Safe Goods/Atn Publishing, 2021).
“Melatonin, glutathione, DHA, magnesium, iron, vitamin D, zinc, thiamine amino acid, B complexes like B1, B2, B6, B12, vitamin D3 and vitamin E have all been found to be deficient in the brains of Alzheimer’s patients. And yet I can’t tell you how many times people tell me that their doctor says all these nutrients don’t do anything. But what about the thousands of peer-reviewed studies that show they’re wrong?
“When we look at brain health, we have to look at so many variables that contribute both to its healthy function as well as its decline.”
There are several mechanisms involved in how nootropics impact cognitive performance, one of which is by altering the levels of neurotransmitters (chemical messengers) in the brain. One such neurotransmitter is glutamate, which is found at high concentrations in the neocortex, the center for executive function and decision-making, and the hippocampus, which plays a major role in learning and memory.
Glutamate activates the NMDA receptor involved in learning and memory, as well as the AMPA receptor responsible for neuroplasticity (the ability of neurons to form and strengthen connections amongst themselves).2
Nootropics also stimulate the release of dopamine, the neurotransmitter that controls the brain’s motivation systems, and they positively affect the brain’s production of choline—essential for synthesizing acetylcholine—in the frontal cortex and hippocampus.
The loss of cholinergic activity in the brain’s hippocampus is understood to be responsible for many symptoms of Alzheimer’s disease. In addition to acting directly on neurotransmitters, nootropics can stimulate receptors vital for brain cell communication, memory formation and learning.2
Some nootropics also guard against the pathological hallmarks of Alzheimer’s disease—so-called “plaques” of amyloid-beta protein (also known as beta-amyloid) and “tangles” of a protein called tau, both of which disrupt communication between brain cells, eventually killing them.
Amyloid-beta is a fragment of a larger protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. But in an unhealthy brain, they accumulate and clump together between the neurons in the brain, blocking information transfer.
Amyloid-beta accumulation is accompanied by the development of twisted fibers of tau protein within the neurons that inhibit their ability to transport nutrients.3
To boost cognitive function and mitigate Alzheimer’s and dementia, the most effective nootropics must be able to cross the blood-brain barrier, support the birth of new neurons (a process called neurogenesis), support brain plasticity, reduce the development of amyloid-beta plaques, provide antioxidant support to reduce free radical toxicity, reduce or inhibit inflammation, protect against cell death and support mitochondrial function.
Studies show that natural nootropics are effective in boosting cognitive performance in healthy individuals. For example, a daily dose of Bacopa monniera extract had cognitive enhancing effects after 90 days.6 Ginkgo biloba was found to have a positive influence on working memory in men between the ages of 50 and 61,7 and ginseng has also been shown to improve memory and even modulate electrical signaling in the brain.8 Ashwaganda (Withania somnifera) improves cognitive and psychomotor performance.9 L-theanine improves verbal fluency and executive function scores.10 Supplementation with lutein and zeaxanthin improves cognitive function in young adults.11 Clinical trials of hesperidin, found in citrus fruit, have shown that drinking hesperidin-rich juice can significantly improve blood flow to the brain as well as executive function and memory recall.12 The list goes on and on.
Unfortunately, most doctors haven’t got a clue about the efficacy of natural nootropics to help those suffering from cognitive problems, let alone those people hoping to improve their mental acuity and brain function in order to up their game at school and at work.
“I can’t tell you how many times I’ve had a patient come in and they’ve been struggling with psychiatric issues or they’re struggling with memory problems, and a lot of times they’ll be told it’s just normal aging,” says Dr Brush. “They’re put on medications approved for use for dementia or cognitive decline that have really relatively poor efficacy. By the time they get to me, they’ve been on those medications for months or years and they’re still declining.
“I tell them, ‘Let’s look at nutrition. Let’s look at lifestyle. Let’s look at inflammation. Let’s look at exercise and other types of things that may be helpful.’ Bottom line, adding more medication and not making any changes to what you’re doing is not going to solve any problems, let alone enhance your life.
don’t do anything. But what about the thousands of peer-reviewed studies that show they’re wrong?
“When we look at brain health, we have to look at so many variables that contribute both to its healthy function as well as its decline.”
There are several mechanisms involved in how nootropics impact cognitive performance, one of which is by altering the levels of neurotransmitters (chemical messengers) in the brain. One such neurotransmitter is glutamate, which is found at high concentrations in the neocortex, the center for executive function and decision-making, and the hippocampus, which plays a major role in learning and memory.
Glutamate activates the NMDA receptor involved in learning and memory, as well as the AMPA receptor responsible for neuroplasticity (the ability of neurons to form and strengthen connections amongst themselves).2
Nootropics also stimulate the release of dopamine, the neurotransmitter that controls the brain’s motivation systems, and they positively affect the brain’s production of choline—essential for synthesizing acetylcholine—in the frontal cortex and hippocampus.
The loss of cholinergic activity in the brain’s hippocampus is understood to be responsible for many symptoms of Alzheimer’s disease. In addition to acting directly on neurotransmitters, nootropics can stimulate receptors vital for brain cell communication, memory formation and learning.2
Some nootropics also guard against the pathological hallmarks of Alzheimer’s disease—so-called “plaques” of amyloid-beta protein (also known as beta-amyloid) and “tangles” of a protein called tau, both of which disrupt communication between brain cells, eventually killing them.
Amyloid-beta is a fragment of a larger protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. But in an unhealthy brain, they accumulate and clump together between the neurons in the brain, blocking information transfer.
Amyloid-beta accumulation is accompanied by the development of twisted fibers of tau protein within the neurons that inhibit their ability to transport nutrients.3
To boost cognitive function and mitigate Alzheimer’s and dementia, the most effective nootropics must be able to cross the blood-brain barrier, support the birth of new neurons (a process called neurogenesis), support brain plasticity, reduce the development of amyloid-beta plaques, provide antioxidant support to reduce free radical toxicity, reduce or inhibit inflammation, protect against cell death and support mitochondrial function.
A 2010 review of the research on synthetic and prescription cognitive enhancers found that they can have a wide range of effects in the same person, boosting some mental processes while simultaneously impairing others. Methylphenidate (Ritalin), for example, had a positive effect primarily on spatial working memory, but no consistent evidence for any other positive cognitive changes. Modafinil, prescribed for narcolepsy, had no effect on memory or mood, and only moderately improved attention and task-related motivation.1
It’s also unclear whether experimental use of synthetic and prescriptive nootropics under laboratory conditions can translate into everyday performance and functioning.
There are additionally adverse side-effects to consider, most of which outweigh the beneficial effects, particularly in young people whose brains are still developing. Methylphenidate has over 50 known side-effects ranging in severity from nervousness, vomiting, heavy sweating and weight loss to chest pain, seizures, depression and hallucinations.
Modafinil has about the same number of side-effects including nosebleeds, headache, back pain and confusion, vision impairment, uncontrollable shaking, difficulty breathing and suicidal thoughts. Donepezil (Aricept) is responsible for side-effects including joint pain, incontinence, bloody stool, vomit that looks like coffee grounds, seizures, hallucinations and abnormal dreams.
And this laundry list doesn’t take into account the possible negative effects of interactions between synthetic and prescription nootropics and other prescription drugs. Over 500 prescription drugs are listed as having possible adverse effects when combined with donepezil alone.
The effectiveness of synthetic and prescription nootropics is suspect even in the patients they are thought to benefit the most. For example, some clinical studies have shown that piracetam has no beneficial effect on cognitive function even in people with dementia or cognitive impairment.2
Treatment of dementia with drugs like donepezil and memantine results in “clinically marginal improvement” in cognition and global assessment of dementia.3 Researchers at St. Michael’s Hospital in Toronto, Canada found that the nootropic drugs donepezil, rivastigmine, galantamine, and memantine lost “all benefits” after 18 months of treatment.
“I’ve lost three family members to Alzheimer’s and dementia, including my dad,” says Michael Edson, MA, LAc , cofounder of Natural Eye Care™, a complementary care practice for eye disease in New York and author of the book Natural Brain Support.
“Within three years my uncle went from being a partner in a law firm to a man who couldn’t even recognize his own family. And what I found most frustrating were the two main drugs prescribed for these conditions, donepezil and memantine. They hardly do anything. At best they may slow down the progression, but after a while they don’t work at all.”
Dr Dale Bredesen, noted neurological researcher, University of California professor, founder of the Buck Institute for Research on Aging and bestselling author of The End of Alzheimer’s (Avery, 2020) concurs. “Neurodegenerative disease therapeutics has been, arguably, the field of greatest failure of biomedical therapeutics development,” he writes.
“Patients with acute illnesses such as infectious diseases, or with other chronic illnesses, such as cardiovascular disease, osteoporosis, human immunodeficiency virus infection, and even cancer, have access to more effective therapeutic options than do patients with Alzheimer’s disease or other neurodegenerative diseases . . . There is not a single therapeutic that exerts anything beyond a marginal, unsustained symptomatic effect, with little or no effect on disease progression.”3
Studies show that natural nootropics are effective in boosting cognitive performance in healthy individuals. For example, a daily dose of Bacopa monniera extract had cognitive enhancing effects after 90 days.6 Ginkgo biloba was found to have a positive influence on working memory in men between the ages of 50 and 61,7 and ginseng has also been shown to improve memory and even modulate electrical signaling in the brain.8 Ashwaganda (Withania somnifera) improves cognitive and psychomotor performance.9 L-theanine improves verbal fluency and executive function scores.10 Supplementation with lutein and zeaxanthin improves cognitive function in young adults.11 Clinical trials of hesperidin, found in citrus fruit, have shown that drinking hesperidin-rich juice can significantly improve blood flow to the brain as well as executive function and memory recall.12 The list goes on and on.
Unfortunately, most doctors haven’t got a clue about the efficacy of natural nootropics to help those suffering from cognitive problems, let alone those people hoping to improve their mental acuity and brain function in order to up their game at school and at work.
“I can’t tell you how many times I’ve had a patient come in and they’ve been struggling with psychiatric issues or they’re struggling with memory problems, and a lot of times they’ll be told it’s just normal aging,” says Dr Brush. “They’re put on medications approved for use for dementia or cognitive decline that have really relatively poor efficacy. By the time they get to me, they’ve been on those medications for months or years and they’re still declining.
“I tell them, ‘Let’s look at nutrition. Let’s look at lifestyle. Let’s look at inflammation. Let’s look at exercise and other types of things that may be helpful.’ Bottom line, adding more medication and not making any changes to what you’re doing is not going to solve any problems, let alone enhance your life.”
Nutrients to enhance brain health and counteract cognitive decline are many and varied. Some of the most important are:
Acetyl l-carnitine (ALCAR) increases mitochondrial function and decreases production of free radicals, slowing the development of Alzheimer’s disease. It also raises levels of nerve growth factor and increases the neurotransmitter acetylcholine. Suggested dose: 500 mg along with alpha-lipoic acid 150–300 mg/day
Ashwaganda reduces accumulation of amyloid-beta and protects neurons, and may help to reverse Alzheimer’s symptoms. Suggested dose: 500 mg twice per day with meals
Astaxanthin combined with DHA enhances learning and memory while reducing issues with tau protein, mitigating potential build up of tangles. Suggested dose: 6 –12 mg/day
Bacopa monnieri extract has neuroprotective effects and is a traditional alternative therapy for Alzheimer’s disease, improving circulation to the brain. It protects neurons from amyloid-beta plaque buildup and death. Suggested dose: 150 –300 mg/day
Baicalein protects neuron signaling and memory function by preventing amyloid-beta buildup in the hippocampus. Suggested dose: 200–800 mg, once in the morning and once at night
Citicoline is a choline precursor possibly effective in treating traumatic brain injury, vascular dementia and brain aging. Suggested dose: 250 mg/day
DHA (docosahexaenoic acid, found in fish oil) is an important component of the cell membranes of neurons, and also promotes BDNF, a protein that supports cognitive function and neurogenesis. Suggested dose: 1,000–4,000 mg/day
Ginkgo biloba promotes new brain cells , raises BDNF levels and reduces amyloid-beta plaque buildup. Suggested dose: 120–240 mg/day
Glutathione is the most abundant antioxidant found in the brain and has documented anti-aging properties. Glutathione levels are depleted in Alzheimer’s patients. Suggested dose: 700–900 mg/day if taken in tablet form, or look for a liposomal formula that can be taken under the tongue, which is claimed to improve absorption
Grape seed extract is a potent antioxidant that protects the nervous system from reactive oxygen species. Suggested dose: 300–600 mg/day
Hesperidin reduces cognitive impairment and oxidative stress in animal models of Alzheimer’s. Suggested dose: 100–500 mg per day
Lycopene is neuroprotective and reduces oxidative stress, suppressing production of inflammation in the body. Suggested dose: 3 mg/day
Magnesium reduces the blood brain barrier permeability and promotes the clearance of amyloid-beta from the brain. Suggested dose: 3,000–6,000 mg/day
Melatonin protects the cholinergic system and is anti-inflammatory. It promotes sleep, which reduces stress and inflammation. Suggested dose: 1 –3 mg at bedtime
Olive leaf extract counteracts amyloid-beta plaque generation and inhibits tau protein tangles. Suggested dose: 500 mg/day with or without food
Phosphatidylserine improves memory, mood and cognition in the elderly, and improves learning, brain function and vocabulary in Alzheimer’s patients. Suggested dose: 100–400 mg/day
Most people have experienced what is termed “brain fog,” the sense of being forgetful, with a clouded mind, poor concentration and difficulty thinking and communicating, accompanied by low overall motivation. Michael Edson attributes the causes of brain fog and poor cognitive function in general to several factors including hormonal changes, chronic fatigue, inflammation and oxidative stress, dehydration, food allergies, exposure to toxins, celiac disease and, last but not least, poor diet and nutrition.
If this sounds like you, here are some of the nootropics to consider, which Edson suggests specifically for brain fog.
Acetyl l-carnitine—500 mg
Alpha-lipoic acid—crosses the blood brain barrier to support production of acetylcholine, the most prominent neurotransmitter in the brain linked to learning and memory; 600 mg daily
B vitamins—follow label instructions
Bacopa monnieri extract—150 to 300 mg daily
Choline alfoscerate, also called alpha-GPC—improves memory retention, boosts brain function and mental clarity; 400 mg three
times daily
Ginkgo biloba—120 mg to 240 mg daily
Ginseng—improves thinking, concentration, memory and physical endurance; 200 to 400 mg daily
Huperzine A—helps clear the mind and improve cognitive function. Increases acetylcholine in the brain; 300 to 500 mcg per day
Iron—iron deficiency is a characteristic of brain fog and impaired brain function. Helps with neuron growth and learning; 65 mg three times daily
Medium chain triglycerides (MCTs)—improve cognitive function; 1 tsp up to 1 Tbsp per day
Omega-3 fish oil—supports cerebral blood flow and reduces inflammation; 250–500 mg combined EPA and DHA daily
Phosphatidylserine—enhances cell to cell communication while supporting the growth of neurons and their maintenance; up to 400 mg daily
Rhodiola rosea—reduces mental and physical fatigue; 400 to 600 mg daily
Additional tips: Get in at least 20 minutes of aerobic exercise five days a week. Manage stress with practices such as yoga and meditation and get plenty of sleep.
A 67-year-old woman came to Dr Dale Bredesen, founder of the Buck Institute for Research on Aging, suffering from two years of progressive memory loss. She had a demanding analytical job, and gradually found herself unable to analyze data or prepare reports. She couldn’t recall what she’d just read and was no longer able to remember numbers. She also began to have trouble driving her car even on familiar roads. She confused the names of her pets and forgot where the light switches were in her home. Upon consulting her physician about her problems, she was told there was nothing he could do about it.
In despair and on the verge of suicide, she was referred by a friend to Dr Bredesen, who put her on a program that included an anti-inflammatory diet and supplements of curcumin, vitamin B12, DHA/EPA, ashwaganda, Bacopa monniera, vitamins D3 and K2, citicoline, coenzyme Q (ubiquinol), alpha-lipoic acid, PQQ (pyrroloquinoline quinone), NAC (N-acetyl cysteine), acetyl-L-carnitine, selenium, zinc, resveratrol, ascorbate, thiamine and pantothenic acid. Melatonin was prescribed to help her sleep. Additionally, she exercised 30–60 minutes, 4–6 days per week, and started a personalized program of yoga.
After three months, all her symptoms disappeared. She was able to keep her job, drive her car, remember telephone numbers without difficulty, read and retain the information. She noted that her memory was better than it had been in many years. Two and a half years later, at age 70, she is still going strong and continues to work full-time.1
PQQ (pyrroloquinoline quinone) prevents mitochondrial dysfunction and improves motor function and cognitive impairment. Suggested dose: 10–20 mg/day
Quercetin protects brain cells against excitotoxicity. Suggested dose: 250–500 mg once or twice per day
Resveratrol has anti-inflammatory and anti-oxidative effects, and it helps prevent neurodegeneration caused by amyloid-beta peptides. Suggested dose: 125 mg/day
Theanine increases BDNF, reduces stress-related symptoms and sleep disturbances in Alzheimer’s patients and improves cognitive and executive function. Suggested dose: 100–200 mg per day
Vitamin B complex, as vitamin B deficiencies are found in Alzheimer’s patients. Suggested dose: follow label instructions
Vitamin D aids in neuroprotection and and neurological development. Suggested dose: 2,000–5,000 IU/day
Zeaxanthin inhibits amyloid-beta aggregation and improves cognitive function. Suggested dose: 2–12 mg per day
Aged garlic boosts natural levels of glutathione, supports memory and cognitive capacity and slows down amyloid-beta accumulation.
Berries, including blueberries, mulberries, raspberries, blackberries and strawberries, all have a neuroprotective effect as antioxidants, reducing inflammation.
Coffee. Quercetin found in coffee beans is neuroprotective, and coffee drinking is associated with a reduced risk of Alzheimer’s disease. Drink 1 to 3 cups per day depending on personal biochemistry.
Ginger root reduces memory impairment by protecting neurons in the hippocampus.
Mushrooms. Reishi, lion’s mane, chaga, and maitake all reduce inflammation and have antioxidant effects while mitigating neurodegeneration.
See our March 2021 issue for more on the benefits of mushrooms.
Pomegranate juice has anti-inflammatory and antioxidant properties, and it has been shown to be neuroprotective against Alzheimer’s.
Red sage (salvia) halts the breakdown of acetylcholine, and it may enhance cognition and protect against degenerative disease.
Sulfur-rich foods including cruciferous vegetables like broccoli, cauliflower, cabbage, pak choy, kale, arugula and mustard greens stimulate the production of glutathione naturally in the body.
Resources
Michael Edson, MA, LAc:edsonacupuncture.com
Julie Brush, ND: amenclinics.com/team/julie-brush-nd
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Turning the lights back on
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The drugs don’t work
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