The Benefits of and Science Behind Using Nootropics for Enhanced Brain Function

In this episode, we discuss:

Who can benefit from nootropics and how long does it take?
Citicoline (CDP-choline)
Uridine Monophosphate (UMP)
Phosphatidylserine (PS)
Ginkgo biloba
Bacopa monnieri
Alpinia galanga
Lion’s mane mushroom
How to take nootropics and caffeine

Show notes:

“Citicoline and memory function in healthy older adults: A randomized, double-blind, placebo-controlled clinical trial” by Nakazaki et al.
“Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women” by McGlade et al.
“The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males” by McGlade et al.
“Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy” by Silveri et al.
“Oral supplementation with docosahexaenoic acid and uridine-5’-monophosphate increases dendritic spine density in adult gerbil hippocampus” by T. Sakamoto, M. Cansev, & R.J. Wurtman
“Antidepressant-like effects of cytidine in the forced swim test in rats” by Carlezon et al.
“Effects of phosphatidylserine in age-associated memory impairment” by Crook et al. 
“Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer’s disease and dementia” by MI Moré, U. Freitas, & D. Rutenberg
“Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine” by Kennedy et al. 
“The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial” by Hirayama et al.
“The effects of phosphatidylserine supplementation on cognitive functioning prior and following an acute bout of resistance training in young males” by Parker et al.
“Efficacy of standardized extract of Bacopa monnieri  (Bacognize®) on cognitive functions of medical students: A six-week, randomized placebo controlled trial” by Kumar et al.
“Effect of Bacopa monnieri on cognitive functions in Alzheimer’s disease patients” by Goswami et al
“Effects of a Bacopa monnieri extract (Bacognize®) on stress, fatigue, quality of life and sleep in adults with self-reported poor sleep: A randomized, double-blind, placebo-controlled study” by Lopresti et al. 
“Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial” by Calabrese et al.
“Neuroprotective role of Bacopa monnieri extract in modulating depression in an experimental rat model” by Zaazaa et al.
“Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment: a noncomparative, exploratory clinical study” by D. Zanotta, S. Puricelli, and G. Bonoldi 
“Differential cognitive effects of Ginkgo biloba after acute and chronic treatment in healthy young volunteers” by Elsabagh et al. 
“Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study” by Mashayekh et al.
“Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg” by Herrschaft et al. 
“The effects of Ginkgo biloba extract (LI 1370) supplementation and discontinuation on activities of daily living and mood in free living older volunteers” by L. Trick, J. Boyle, & I. Hindmarch
“Acute Effects of Alpinia galanga Extract on Mental Alertness, Accuracy and Fatigue in Human Subjects: A Randomized, Double-Blind, Placebo-Controlled, Cross-OverStudy” bu Mohan et al.
“Effect of Alpinia galanga on Mental Alertness and Sustained Attention With or Without Caffeine: A Randomized Placebo-Controlled Study” by S. Srivastava, M. Mennemeier & S. Pimple
“Selective enhancement of focused attention by Alpinia galanga in subjects with moderate caffeine consumption” by S. Srivastava
“Neurotrophic and Neuroprotective Effects of Hericium erinaceus” by Szućko-Kociuba et al. 
“The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease” by Yanshree et al.
“Therapeutic Potential of Hericium erinaceus for Depressive Disorder” by Chong et al.
“Hericium erinaceus in Neurodegenerative Diseases: From Bench to Bedside and Beyond, How Far from the Shoreline?” by Brandalise et al.
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Chris Kresser:  Hey everyone, Chris Kresser here. Welcome to another episode of Revolution Health Radio. I’ve been podcasting for almost 15 years, which is crazy. And believe it or not, I’ve never done a full episode on nootropics during that time, so I’m going to make up for that today. Nootropics are substances that improve mental functions like cognition, memory, creativity, motivation, attention and mood. The word nootropic comes from the Greek words ‘noos’ meaning mind and ‘tropos’ meaning a change or turn. So, literally nootropics “turn” or “change” the mind in a beneficial way.
The concept of nootropics has been around since the 1970s, when a Romanian psychologist named Corneliu Giurgea coined the term. He defined nootropics as substances that enhance learning and memory, protect the brain against injury and disease, and have very low toxicity and side effects. Some popular natural nootropics include caffeine, L-theanine, and creatine. More potent synthetic nootropic supplements have also been developed like piracetam, aniracetam, Noopept, and modafinil. Research shows some nootropics seem to work by influencing neurotransmitter systems and stimulating nerve growth in parts of the brain involved in cognitive functions. They may improve communication between neurons and promote brain plasticity, and some also have anti-inflammatory and antioxidant effects to protect brain cells. Nootropics can be incredibly helpful for improving focus, information processing, learning capacity, memory formation, and even mood.
In this episode, I’ll share some of my favorite nootropics, break down the science behind how they influence brain function, and explain how to use them effectively. I’ve deliberately chosen to focus on some newer and lesser known nootropics rather than common ones like caffeine, L-theanine and creatine, simply because there’s already so much information out there about those, and I want to introduce you to some very effective nootropics that you may be less familiar with. Just a warning in advance, this is going to be a pretty dense show with lots of information, because we’ll be covering seven nootropics in depth. So you might want to choose your favorite nootropic that you’re working with already and settle in and listen to this, because it’s going to take a little while. All right, without further ado, let’s dive in.
Before we cover some specific nootropic nutrients and botanicals, it’s worth noting that the most important thing you can do to improve your cognitive function and mood is eat a nutrient-dense, whole-foods diet and follow a healthy, ancestral lifestyle. As powerful as these nootropic compounds I will discuss are, you cannot supplement yourself out of a bad diet and lifestyle. I’m not going to cover the basic diet and lifestyle principles here since I’ve done that at length in many other contexts. My first book, The Paleo Cure, is a great primer if you’re new to an ancestral diet and lifestyle. You can also find free ebooks and other resources on my website ChrisKresser.com.
Who Can Benefit from Nootropics, and How Long Does it Take?
So who might benefit from a nootropic? The short answer is anyone who wants to improve or optimize their cognitive health, memory, learning, focus, attention, mood, resilience, emotional balance, and circadian rhythm. This means probably most people living in the modern world in the 2020s would likely benefit from a nootropic. I mean, who doesn’t want improvements in these areas? That said, there are specific populations that are most likely to see significant benefits with nootropics, including people experiencing brain fog, poor memory, difficulty focusing and concentrating, a tendency to get easily distracted or other cognitive health challenges, [and] people struggling with depression, low mood, mood swings, apathy, demotivation, or anxiety. [Also] people who are dealing with significant stress which leads to sleep difficulties, circadian disruption, fatigue and feeling rundown; entrepreneurs and knowledge workers, creators, artists, and people who want an advantage in mental clarity, focus, creativity, productivity and mental stamina; students, of course, who are seeking to improve their memory and learning and facilitate new understanding and connections; [and] children and adults with [attention-deficit/hyperactivity disorder] (ADHD) and other behavioral issues involving difficulty concentrating, focusing, and staying on task. Nootropics can be an absolute game changer for this population, and are sometimes as effective or more so than stimulant medications. They can also complement and extend the benefits of stimulants, but, of course, you should always speak with your health care provider before combining them. And last but certainly not least, people with dementia, Alzheimer’s [disease], Parkinson’s [disease] or other neurodegenerative conditions. Several of the nootropics we’ll discuss have been shown to protect brain cells from inflammation and oxidative stress, regenerate neurons and increase the number of connections between them, reduce amyloid plaque, boost neuroplasticity, and improve memory focus, attention, and other markers of cognitive health in people who are experiencing significant cognitive decline.
So let’s talk a little bit about how long you need to take nootropics to notice a benefit. In some cases, like with caffeine and synthetics like modafinil, people will feel results almost immediately after a single dose. But with others, especially natural compounds like many of the ones I’ll discuss today, there’s often both an immediate or short-term effect and then a long-term or cumulative effect. For example, some studies have shown that Bacopa monnieri  can improve memory, focus, attention and other aspects of cognitive function within 45 minutes of ingestion. However, these effects tend to increase over time with repeated use. It’s also worth noting that there’s a big range of individual responses. Some people won’t feel much the first time they take a nootropic but may notice significant benefits after a week or two. As a general rule, with some notable exceptions like caffeine, natural nootropics tend to take a few weeks, and up to several months in some cases, to produce their full benefits. Whereas the synthetic nootropics like Piracetam and Modafinil work very quickly. I’d also say that the natural nootropics are more likely to address underlying mechanisms and lead to longer term and more sustained improvements in cognitive function and mood. For example, lion’s mane mushroom, which we’ll discuss more later, has been shown to regenerate brain cells. This is a remarkable effect with long-term benefits, not just an immediate change that fades away, as with some of the short-term nootropics. This is one of the reasons I tend to favor natural nootropics for longer term use. Of course these can also be stacked with shorter term nootropics like caffeine for maximum benefit, and I’ll discuss this later in the episode. With all of this in mind, let’s take a look at seven of my current favorite natural and longer acting nootropics.
Citicoline (CDP-choline)
The first is citicoline. Citicoline, also known as CDP-choline, is a natural compound that plays an important role in supporting brain health and function. It’s an intermediate involved in the synthesis of phosphatidylcholine, a major component of cell membranes, especially in the brain. This helps support the structure and function of brain cells. It increases levels of neurotransmitters like acetylcholine, dopamine, and norepinephrine, which play key roles in cognition, memory, mood, and more. Research has shown that citicoline can improve memory and cognitive performance in both healthy adults and in those with mild cognitive impairment. And some studies suggest it may also help with conditions like dementia and Alzheimer’s [disease]. Citicoline has been shown to reduce depressive symptoms and improve mood and motivation, which may be due to its effects on neurotransmitters like dopamine. Citicoline improves brain health via several distinct mechanisms. After ingestion, it’s metabolized into choline and cytidine. These breakdown products cross the blood brain barrier via specialized transport systems. Once inside the brain, cytidine and choline are resynthesized back into citicoline and incorporated into phospholipid cell membranes. This raises levels of phosphatidylcholine and sphingomyelin, which are critical for membrane integrity.
The choline component is then used to synthesize the neurotransmitter acetylcholine. This cholinergic compound is vital for memory learning, focus, and neural signaling, and more choline availability means more acetylcholine production. Citicoline-derived phospholipids also build neuronal membranes which promote the generation of new brain cells. Richer fluid membranes equate to better electrical signaling between neurons. Citicoline-derived phospholipids also build neuronal membranes which promotes the generation of new brain cells, and richer fluid membranes equate to better electrical signaling between neurons. Citicoline also increases dopamine and norepinephrine levels, as I mentioned. These catecholamine neurotransmitters are essential for concentration, working memory, mood, and more. And finally, as an intermediary metabolite in membrane synthesis pathways, citicoline provides building blocks for repair after stress or injury, and it may shield neurons and their synaptic connections.
Okay, at the risk of getting too deep in the scientific weeds here, I’d like to share more about how citicoline gets converted into uridine and how uridine supports cognitive function and mood. This is an important but lesser known function of citicoline, and it’s also relevant to one of the other nootropics I’m going to introduce next called uridine monophosphate, or UMP. After you take citicoline and it gets absorbed in the blood, the cytidine component crosses the blood-brain barrier and enters brain cells. Here, cytidine gets converted into uridine by the enzyme cytidine triphosphate synthase or CTPS. This uridine then gets phosphorylated into uridine monophosphate, or UMP, which is a critical nucleotide base that makes up vital components of brain cell membranes and neural functionality. UMP is one of the main building blocks for synthesizing phosphatidylcholine and other neuro phospholipids that form gray matter structural membranes and white matter myelin sheath. It combines with phosphatidylserine to support the formation of synaptic vesicle membranes involved in interneural signaling via neurotransmitters like dopamine and acetylcholine, and it facilitates phospholipid production needed for sprouting dendrites, which are the connections between brain cells, regenerating axons and forming new connections during neuroplasticity and long-term potentiation underlying memory and learning.
To summarize this, the cytidine in choline converts to uridine that supports neural membrane health, synapse formation, neuroplasticity, and overall optimal brain function. Uridine’s central role helps explain some of citicoline’s beneficial neurotropic mechanisms for cognitive function. And I think that citicoline, for this reason, is superior to other supplemental forms of choline, like choline bitartrate, for brain health because it readily crosses the blood-brain barrier and it also has this added benefit we just discussed of being converted into UMP, which supports brain health and cognitive function in numerous ways.
So let’s look at some selected studies that demonstrate citicoline’s brain health benefits. A randomized controlled trial of 100 men and women aged 50 to 85 with memory impairment found that 12 weeks of citicoline supplementation improved overall an episodic memory. And I’m going to pause here and remind you that you can always find the transcript and the scientific references for every episode on my website at ChrisKresser.com. Another randomized control trial of 60 healthy adult women found that citicoline significantly improved focus and attention and reduced attentional deficits. In a randomized controlled trial out of the University of Utah involving 75 healthy young men, citicoline improved attention and psychomotor speed and reduced impulsivity. This study has several interesting implications. First, it shows that citicoline works in younger people as well as older adults. Second, it suggests that citicoline may be helpful for improving athletic performance in addition to boosting cognitive function and mood. And this makes sense if you think about it. The brain obviously governs our ability to perform any activity, so sharpening brain function will certainly improve athletic performance. And third, citicoline may be helpful for treating ADHD and other attention-related disorders. Finally, a magnetic resonance spectroscopy study out of Japan found that citicoline increased brain [adenosine triphosphate] (ATP) levels by 14 percent and sped up formation of brain membranes by 26 percent in healthy adults. This is a crucial finding because prior research has shown that maintaining ATP levels and promoting the formation of brain membranes reduces age-related cognitive decline and protects against neurodegenerative conditions like dementia, Alzheimer’s [disease] and Parkinson’s [disease].
There are a few different forms of citicoline available on the market. My favorite is a patented form called Cognizin. It’s allergen-free, water soluble, and it’s supported by several peer-reviewed clinical trials. In fact, all the studies I mentioned when I discussed the mechanisms of actions and benefits of citicoline earlier in the show were performed with Cognizin. Citicoline is often stacked with [docosahexaenoic acid] (DHA) long-chain omega-3 fat, B vitamins like B6, folate, [and] B12, and uridine monophosphate, or UMP, which we’ll discuss next. Studies have shown that combining these nutrients together produces greater benefits than taking any of them alone, and you’ll find that that’s a common theme as we go through this episode. In terms of dosage, the typical dose of Cognizin ranges from 125 to 500 milligrams per day. The lower dose is often used in formulas where other nootropic nutrients are present, whereas the higher dose is used when Cognizin is taken by itself and/or when more support is needed, like in cases of dementia or more serious cognitive or neurological impairment.
Uridine Monophosphate (UMP)
Okay, the next nootropic is uridine monophosphate, or UMP. This is a pyrimidine nucleoside essential for many cellular processes in the body. It plays important roles in the synthesis of nucleotides and phospholipids that are critical for cell membrane function and integrity. Uridine is one of the four repeating structural units of [ribonucleic acid] (RNA). As you might recall from your high school biology class, RNA and [deoxyribonucleic acid] (DNA) are the information carriers in our cells. Uridine is so critical to brain development that it’s a component of breast milk, and it’s now included in baby formula. And it’s essential for optimal cognitive function and memory throughout life. In short, without uridine to make up RNA, DNA couldn’t synthesize proteins and life as we know it would cease to exist. This should give you an idea of just how important uridine is to the brain and overall health. I briefly mentioned some of the ways that UMP improves brain health in the last section on citicoline, but let’s go into a bit more detail.
It increases synaptic plasticity and neurotransmission. UMP provides building blocks for the synthesis of nucleotides and phospholipids needed to produce and maintain cell membranes, synapses, and neurotransmitters in neurons. This supports improved signaling, or communication, between neurons. It promotes neuron growth and development by supporting phospholipid synthesis. UMP helps grow and maintain neuron cell membranes and structure, allowing for the growth of new connections. It improves mood and motivation. Enhanced phospholipid production and neurotransmission is linked to better regulation of mood, reduced anxiety and depression, and improved motivation and drive. And in my clinical experience, I would say that this is one of the most potent and common effects of UMP– improving mood and motivation. It protects neural networks. The membrane building and neuron nourishing abilities of UMP help protect existing connections between neural networks in the brain. And finally, it slows neurodegeneration. Research indicates the neuroprotection and neuroplasticity benefits of UMP supplementation can slow age-related cognitive decline and protect against Alzheimer’s disease.
Our cells synthesize UMP from basic building blocks through something called the de novo pathway, or they can recycle available uridine nucleosides to recover UMP through a salvage pathway. The salvage pathway requires less energy so it’s more common, but some tissues like the brain lack adequate salvage pathway enzymes and uridine synthesis naturally declines with age. While uridine is found in some foods like beets, broccoli, fish, mushroom, oats, and parsley, it’s not very bioavailable in food because it gets broken down in the gut into constituent components and is not absorbed as UMP. The poor synthesis of uridine in the brain and its low bioavailability in food is why supplementation, either indirectly with citicoline or directly with UMP itself, or both, can be so helpful. When it’s taken as a supplement, UMP has been shown to easily cross the blood-brain barrier and raise uridine levels in the brain. And UMP has much better bioavailability as a supplement than dietary sources of uridine.
So let’s look at some selected studies indicating the benefits of UMP. It’s been shown to boost cognitive function and even increase intelligence. A randomized, controlled trial in older adults found that a combination of UMP plus DHA, plus choline, plus vitamins– so again, here’s the synergistic effects of combining different nootropics– for 12 weeks significantly improves scores on cognitive tests measuring learning, memory, reasoning, and information processing speed compared to placebo. Mood also improved significantly based on reduced depression inventory scores. Several other studies have shown that combining UMP with DHA and choline produces better results than taking either alone. In one rigorous animal study with gerbils, researchers found that the combination of DHA, UMP, and choline significantly increased learning and memory. Gerald Wiseman, who is the editor-in-chief of the journal that study was published in said, “Now that we know how to make gerbils smarter, it’s not too far of a stretch to hope that people’s intelligence can also be improved.” UMP can regenerate brain synapses and protect against dementia and Alzheimer’s [disease]. A study out of MIT found that a cocktail of DHA, uridine, and choline significantly increased the concentration of dendritic spines. This is important because the cognitive decline seen in [patients with] Alzheimer’s [disease] is caused by a loss of brain synapses and dendritic spines. So an increase in those spines means that brain synapses have been regenerated. Another study which analyzed the brain extracellular fluid showed that cognitive impairment in Alzheimer’s disease is closely correlated with low uridine levels in the brain. Supplementing with UMP restored concentrations [and] improved phosphopeptide synthesis, synaptic plasticity, and cognitive outcomes in rodent models. Phosphatides like phosphatidylcholine are primary components of neuron cell membranes. More phosphatides allow for greater membrane integrity, fluidity, and signaling. They drive the formation of new dendritic spines and synapses between neurons, and more synapses improves neural network connectivity and signaling. Once again, combining DHA and choline with UMP led to greater increases in phosphatides than any of the single compounds alone.
UMP has also been shown to elevate mood and fight depression. Researchers believe that it improves mood and alleviates depression by making membranes more resilient and improving neurotransmitter signaling. Several animal studies have shown that UMP produces antidepressant effects by boosting dopamine and acetylcholine activity, along with improving hippocampal function. As I mentioned earlier, improvement in mood is one of the most notable effects of UMP, in my experience. Some of my patients have described this combination of elevated mood and sharper mental clarity as “turning the lights back on”. They feel more relaxed, focused, happier, and smarter, and that’s how I feel when I take it myself. UMP has been shown to increase focus and attention without inducing anxiety. Though there’s less research on this topic, many anecdotal reports from people with ADHD suggest that UMP can improve cognition without triggering anxiety or mood changes. I’ve used it for this with patients in my practice with great success, and this effect is supported by a study showing that uridine reduces the side effects associated with medication that affects dopamine and [gamma-aminobutyric acid] (GABA) neurotransmission.
So if UMP is this effective and safe, why haven’t you heard of it? Well, it’s simple. Since uridine is a natural element, it cannot be patented by drug companies. And if it can’t be patented, Big Pharma can’t make money off it. Two thirds of medical research is sponsored by the pharmaceutical industry, so there’s little incentive for companies to fund additional UMP trials and publicize those results. I wish this wasn’t the way our system works, but unfortunately it is. This same phenomena happens with many other natural compounds beyond UMP. In terms of sourcing, there are two main ways to increase UMP levels with supplements. One is to take citicoline. Earlier in the show I explained how citicoline is broken down into citidine and choline in the gut. Citidine can then be converted into uridine by the enzyme CTPS. This uridine then gets phosphorylated into uridine monophosphate. The second more direct way is to supplement with UMP itself. It easily crosses the blood-brain barrier, where it provides all of the benefits we’ve discussed. As I’ve noted, the effects of UMP are increased when it’s stacked with DHA and choline. DHA comprises 60 percent of the brain and is most prominent in the phospholipid membrane of the neurons. Combining DHEA with UMP leads to a greater increase in synaptic phosphopeptides than either compound alone, and adding choline amplifies the effects even further. Citicoline is the preferred form because it will further increase UMP levels, and magnesium and B vitamins have also been shown to potentiate the action of UMP. The recommended dose is 150 to 250 milligrams. Again, the lower end of this dose would be used in a formula containing multiple nutrients and the higher end would be for standalone use or for more aggressive support.
Phosphatidylserine (PS)
Phosphatidylserine, or PS, is the next nootropic I’d like to discuss. It’s a phospholipid compound found in the cell membranes of neurons. It plays a critical role in cell cycle signaling and maintaining cellular function, especially in the brain. PS stimulates the production of nerve growth factor, or NGF. Nerve growth factor supports long-term potentiation, which is needed for memory formation. PS also plays a critical role in building mitochondria, which are the batteries, or energy centers, of each brain cell. Many experts believe that PS is one of the most effective and important nootropics we have access to. It keeps our brain cells healthy, promotes alertness, attention, cognition, memory, recall, and mood. PS supports brain health via several mechanisms. It increases membrane fluidity. It influences the movement and function of proteins within the cell membrane, which is crucial for neurotransmitter release and receptor activity, and that functioning is vital for cognitive tasks like learning memory and reasoning. It enhances neurotransmitter synthesis and release. PS can affect the release of neurotransmitters like acetylcholine, dopamine, and serotonin, which are involved in mood regulation, memory, and learning. And by modulating the availability of those neurotransmitters, PS can support cognitive function and positively affect mood. PS has also been shown to have neuroprotective effects. It can help mitigate the damage caused by oxidative stress and reduce the risk of apoptosis, or cell death, thus preserving neuronal integrity. That’s critical for preventing cognitive decline associated with aging and other neurodegenerative conditions. PS also helps to regulate cortisol levels. As [I’m sure] you know, cortisol is a stress hormone that can negatively impact cognitive function and mood when it’s chronically elevated. By modulating the stress response, PS can contribute to improved stress resilience, better mood regulation, and better cognitive performance. So let’s look at a few studies.
A randomized controlled trial involving almost 150 elderly participants with cognitive decline found that PS significantly improved performance on memory tests including recall of names and faces. A double-blind, placebo-controlled study found that a combination of PS and phosphatidic acid significantly improved memory and prevented winter blues. It also preserved daily functioning, whereas the patients on placebo saw a significant decline in this area. If you recall, UMP also increases phosphopeptides, so combining PS with UMP may lead to greater benefits than either compound alone. A randomized controlled trial combining PS and Ginkgo biloba found improvements in secondary memory performance and speed of task performance, along with greater calmness and stress tolerance. Ginkgo is another of my top seven nootropics and we’ll discuss it more shortly. And again, you may be noticing a theme here. These nootropics tend to have synergistic effects when they’re combined. A double-blind RCT (or randomized control trial) of almost 40 kids aged four to 14 years old found significant improvements in ADHD symptoms, short-term memory and attention, and impulsivity. PS was well-tolerated with no adverse effects, which is important given the high prevalence of side effects associated with many ADHD medications. And finally, phosphatidylserine has been shown to reduce stress and increase performance in runners, cyclists, and golfers. A randomized, double-blind, placebo-controlled, crossover pilot study involving 18 men aged 18 to 30 found that PS supplementation significantly increased cognitive function prior to exercise. As we saw with citicoline and UMP, better brain health and cognitive function leads to improvements in physical and athletic performance.
The body synthesizes PS through a series of enzymatic reactions involving the exchange of head groups of phospholipids. The efficiency of those enzymatic processes can be influenced by genetic factors, nutrient availability, and the presence of certain health conditions or diseases. PS can also be obtained from the diet, with higher concentrations found in certain foods like organ meats, particularly liver and kidney, and fish. As a side note, this is a lesser known but very important benefit of consuming organ meats– the phosphatidylserine content. Research suggests that PS levels in the brain may decline with age, which could contribute to the decrease in cognitive function and increase in cognitive decline seen in elderly populations. This decline in PS levels might be due to a combination of reduced biosynthesis and increased demand for PS in cellular repair and maintenance processes that occur with aging. Overall health status including metabolic health, liver function, and lifestyle factors like exercise and stress can impact PS synthesis and turnover. Chronic diseases and high stress levels, for example, might affect the body’s ability to produce and maintain optimal levels of PS. So for all of these reasons, supplementing with PS can be helpful, especially as we age.
PS supplements have historically been derived from cow brains, soy, and sunflower. Bovine cortex PS from cow brains was one of the first commercially available forms, but there are concerns about the potential transfer of prion diseases. For this reason, soy- and sunflower-derived PS supplements are more commonly used now. Between soy and sunflower PS, there is some evidence that soy phosphatidylserine may have greater bioavailability and ability to support cognitive function. A double-blind, placebo-controlled trial in elderly patients with memory complaints found that 300 milligrams per day of soy-derived PS improved memory and cognition, while sunflower PS showed no significant benefit over placebo. Researchers believe that soy PS may incorporate more efficiently into neural cell membranes compared to sunflower PS due to differences in phospholipid structure. The fatty-acid chains in soy PS may make them more compatible with and recognizable to human cell membranes. I’m generally not a huge fan of supplements derived from soy for two reasons– most soybeans are GMO, and some people are sensitive to soy proteins. The good news here though is that there are some high quality PS ingredients that are derived from soy but do not contain any traces of soy protein. PS is typically made from soy lecithin, which contains different phospholipids, including PS, and then it’s highly purified to enrich the PS component through a process called phospholipid exchange. That removes any traces of soy protein so that the only thing left is the phosphatidylserine itself. And some of these higher quality PS ingredients are also non-GMO. So those are two things to look out for if you’re looking for a PS supplement.
In terms of stacking, PS has shown the best results when combined with DHA, as well as compounds that increase phosphatides like UMP or citicoline, and Ginkgo biloba. The recommended dosage of PS is 100 to 300 milligrams per day. As with the other nootropics we’ve talked about, lower doses are more common when PS is combined with synergistic nutrients and the higher end is typically for standalone use and more intensive therapy.

Unlock your brain’s full potential in our latest #RevolutionHealthRadio episode! We explore the power of nootropics like citicoline, UMP, PS, Bacopa monnieri, and Ginkgo biloba to boost cognition, memory, and mood. Dive deep into the science with us! #BrainHealth #Nootropics

Bacopa monnieri
Okay, let’s move on to Bacopa monnieri. This is an herb commonly known as brahmi that’s been used in Ayurvedic medicine for centuries to enhance cognitive function and mental clarity. It does this via several mechanisms. Number one, it contains powerful antioxidants called bacosides that protect the brain from oxidative stress and improve cell signaling. This protection may help maintain the integrity of brain cells and improve cognitive function. Second, it improves neurotransmitter modulation by regulating the production and signaling of neurotransmitters like serotonin, acetylcholine, and GABA. These neurotransmitters are associated with mood regulation, memory, and better communication between neurons. Number three, Bacopa can improve working memory, information processing speed, attention, and other measures of cognitive performance. Number four, Bacopa helps preserve the structure and function of nerve cells. It also promotes synapse growth and dendritic branching, which may enhance learning and memory capacity over time. Number five, Bacopa has adaptogenic properties. It modulates the [hypothalamic-pituitary-adrenal] (HPA)-axis and cortisol levels, and protects neurons from stress-related toxicity and apoptosis, or cell death. Reducing stress and anxiety improves mental clarity and focus. And six, Bacopa improves cerebral blood flow, which increases the delivery of oxygen and nutrients to the brain. Ginkgo biloba is well-known for this, and we’ll talk about that shortly, but Bacopa also has this effect. Animal research has found that Bacopa significantly increased cerebral blood flow in the hippocampus and cerebral cortex compared to controls. The compounds bacosides A and B and Bacopa are thought to activate eNOS, or nitric oxide signaling, leading to a cascade that results in nitric oxide-mediated vasodilation, expanding the blood vessels and therefore enhanced circulation.
Let’s talk about a few studies. A six-week RCT of 60 healthy medical school students found that 300 milligrams a day of Bacopa significantly improved several parameters of cognitive function including memory, focus, and attention. The students experienced a 28 percent increase in recognition, recall, and memory, and a 53 percent improvement in immediate recall of logical material and language. So this is a great nootropic for students or anyone who wants to increase their mental capacity. A study of 39 patients with Alzheimer’s disease found that Bacopa led to significant cognitive improvements including a 73 percent increase in focus, attention, and concentration, a 33 percent higher score in language comprehension, reading, and writing, and a 29 percent improvement in spatial memory. A study of almost 90 healthy males with self-reported sleep problems found that Bacopa significantly improves sleep, energy, and quality of life. This included positive changes in alertness upon awakening, emotional wellbeing, general health and pain, an increase in nighttime melatonin, a decrease in C-reactive protein, which is an inflammatory marker, and a trending increase of morning cortisol levels. A study of 54 participants aged 65 and over found that Bacopa improved mood and reduced depression scores as measured by the Center for Epidemiologic Studies Depression Scales, or CESD-10. Animal studies have also found that Bacopa improves depression as much or more than prescription antidepressants. Finally, Bacopa has been shown to improve cognition, mood, and sleep in kids with ADHD and other behavioral disorders. Significant improvements were also seen in hyperactivity and attention deficit domains.
Sourcing for Bacopa is pretty important. A majority of Bacopa in India is grown in rice paddy fields in East and Northeast India, as a secondary crop or after the rice crop harvest. Because it’s commonly grown with rice, the soil is known to have trace residue of herbicides and pesticides that are commonly used in rice agriculture and harvest. As Bacopa became a secondary crop for rice farmers, little care was taken [in the] drying or cleaning of the Bacopa post-harvest. The traditional open drying practices were not controlled to protect the crop from possible fungal growth during storage, and care to avoid easily absorbed pesticides and herbicides was not traditionally taken into consideration. This means that a lot of commercial varieties of Bacopa on the market are susceptible to adulteration from toxins, pesticides, herbicides and heavy metals, as well as possible fungal contamination from inadequate storage. For these reasons, my preferred brand of Bacopa is called Bacognize from Verdure Sciences. They’ve forged lasting relationships with tribal families and family farms, and the final Bacopa product is clean, with controlled drying and collection techniques which protect  botanical integrity while providing a reliable livelihood and income to the families that they work closely with. They use microscopy, macroscopy, and chemical methods for identifying Bacopa, they trace the source, and they test for chemicals and toxins to ensure the authenticity and purity of their Bacopa. It’s also non-GMO and certified glyphosate residue-free, and it has demonstrated activity at the serotonin 5-HT1A receptor, which is important because that’s one of the main mechanisms of action mentioned in many of the clinical studies. And it’s of course supported by peer reviewed studies.
So for stacking, there’s a little bit less information on stacking Bacopa with other nootropics compared to some of the ones we just discussed. But anecdotally, many neuro hackers combine Bacopa with PS, or phosphatidylserine, which assists in neuronal communication. And combining these two together may improve cognition better than taking either alone through these synergistic relationships. One 2014 study did examine the combination of Bacopa, PS, vitamin E and astaxanthin, which is an antioxidant, and found that this combination improved memory and other aspects of mental clarity in participants with cognitive impairment. The optimal dose of Bacopa can vary significantly based on the type of extract used and other individual factors. For standardized Bacopa extracts containing 55 percent bacosides, a dosage of 300 milligrams per day is commonly recommended for standalone use. Sometimes a lower dose will be used in formulas, [and] sometimes a higher dose is used for people with significant cognitive issues. For example, the study I mentioned earlier on patients with Alzheimer’s disease used a 600-milligram per day dose. So there’s some flexibility there depending on what your particular goals and needs are. Bacopa is fat soluble, so it’s best taken with a meal that contains fat or with a small amount of MCT or coconut oil if it’s taken in a fasted state.
Ginkgo biloba
The next nootropic is Ginkgo biloba. Ginkgo biloba is an herb extracted from the dried leaves and seeds of the Ginkgo tree, which is one of the oldest living tree species on Earth. Botanists consider it a living fossil dating back at least 270 million years. Ginkgo is so hearty [that] it has continued to survive even after major extinction events like the asteroid impact that took out the dinosaurs. Individual Ginkgo trees can survive for well over 1000 years. Some Ginkgo trees in China are thought to be as old as 3000 years and four Ginkgo trees survived the atomic explosion in Hiroshima despite being only one thousand meters from the bomb’s epicenter. This is clearly a very special tree and it produces a very special medicine. Ginkgo has been used in TCM, or traditional Chinese medicine, for almost 5000 years. It appeared in the Chinese Materia Medica data at 2800 BC, and is still used today in TCM for upper respiratory complaints, swelling and edema, vascular function, and brain health. Ginkgo has five major effects. Number one, it improves memory and cognition, especially in those with dementia or age-related cognitive impairment. Proposed mechanisms include increased blood flow to the brain, much like Bacopa, protection against neuronal damage, and modulation of neurotransmitter systems involved in memory like acetylcholine and glutamate. Multiple meta-analyses of clinical trials support these effects. Number two, Ginkgo is neuroprotective. Its extracts contain antioxidant and anti-amyloid compounds that may protect neurons from damage. Clinical trials show slower progression in [patients with] dementia and Alzheimer’s [disease] taking Ginkgo. Number three, it promotes enhanced alertness and focus. Ginkgo is thought to influence multiple neurotransmitters and enhance oxygen utilization and brain tissue. And some studies support benefits for ADHD symptoms as well. Number four, it increases peripheral and cerebral blood flow. Ginkgo promotes blood flow to the peripheral tissues, including the hands and feet, sex organs, and brain. It also increases blood circulation in the brain, which improves oxygen and glucose availability to neurons and boosts memory, recall, cognition, and learning. Number five, it relieves anxiety and depression and elevates mood. Ginkgo extracts modulate serotonin receptors and the stress hormone cortisol to help mitigate anxiety, stress, and possibly depression for some people.
If you do a deep dive on Ginkgo, you’ll find that the research on its efficacy is mixed, with some studies showing benefits and others not. This is almost certainly due to the fact that only Ginkgo extracts are effective. Many studies use the whole herb powder, which is not standardized and has low potency. Almost all the studies using extract show benefits. Ginkgo does have some important contraindications to be aware of. It has a mild blood thinning effect, and this can result in increased risk of bleeding when used concurrently with antiplatelet agents, anticoagulants, and other medications that thin the blood. It interacts with [selective serotonin reuptake inhibitors] (SSRIs) and antidepressants. Ginkgo acts as a monoamine oxidase inhibitor, or MAOI. It inhibits the breakdown of monoamine oxidase, which breaks down dopamine. This leads to higher dopamine levels and explains why Ginkgo can reduce anxiety levels. However, combining MAOIs and SSRIs, [which are both] antidepressants, can significantly increase the risk of serotonin syndrome, which is a condition that occurs when there’s an excessive accumulation of serotonin in the body. [It] can lead to symptoms like confusion, rapid heart rate, high blood pressure, dilated pupils, fever, agitation, and in some cases, seizures or even unconsciousness. MAOIs and SSRIs [both] affect serotonin levels in the brain, but in different ways. MAOIs work by inhibiting the enzyme that breaks down serotonin, thereby increasing its levels, while SSRIs prevent the reuptake of serotonin back into neurons, which also increases its levels. For these reasons, it’s considered unsafe to take Ginkgo concurrently with SSRIs or other compounds that affect serotonin levels like St. John’s wort, BuSpar, or even high doses of melatonin above 10 milligrams per day. Finally, a few isolated clinical reports have associated seizures with Ginkgo use in patients that are taking medications used to lower seizure threshold, which include Diprivan, Mexitil, amphotericin B, penicillin and a few others. So Ginkgo is very safe and well-tolerated for most people, but if you’re taking blood thinners, SSRIs, or medications or herbs that affect serotonin levels like St. John’s wort or BuSpar, or you’re taking drugs that lower the seizure threshold, you should definitely speak with your health care provider before you take it.
All right, let’s talk about some selected research studies. One study of 240 patients with mild dementia showed that Ginkgo extract taken daily for six months improved memory, attention, processing speed, and quality of life compared to placebo. As expected, Ginkgo also increased blood flow in the prefrontal cortex as evidenced by brain scans. A study of 20 [patients with] Alzheimer’s [disease] found that Ginkgo extract over 12 weeks significantly improved cognitive scores and selectively increased blood flow in the frontal lobe and hippocampus on [magnetic resonance imaging] (MRI) scans. A study of 40 healthy, older adults showed that Ginkgo, in just four weeks, improved working memory [and] accuracy, increased vigor, and increased resting [electroencephalogram] (EEG) theta activity, which indicates improved alertness. Another study of 30 healthy older adults who took Ginkgo for four weeks showed enhanced fluid intelligence skills like abstract reasoning compared to placebo. Ginkgo literally made them smarter. So, much like we discussed before with UMP, Ginkgo can literally increase intelligence and make you smarter. Finally, a study with 1600 men and women who took Ginkgo or placebo daily for four months, six months, or 10 months found that Ginkgo improved activities of daily living, mood, and alertness in all of the groups. Activities of daily living were defined as multitasking, completing household tasks, concentrating during conversation, remembering important dates, and giving and following directions. But a critical finding in this study was that participants who took Ginkgo for the longest reported the greatest improvement in all ratings. Ten continuous months of supplementing with Ginkgo was more effective than six months, which in turn was more effective than four months.
For sourcing, make sure to choose a Ginkgo leaf extract rather than a Ginkgo nut extract or a whole herb powder. Leaf extracts are what have been used traditionally and studied most in the scientific literature and they’re more potent and beneficial. Note that not all extracts are created equal. The ratio of the extract, like 1:1 or 4:1, refers to how concentrated it is. For example, with a 4:1 extract, for every four parts of the original material, only one part remains in the extract. This higher concentration is achieved through various extraction methods like using water or alcohol. So a 4:1 extract will be roughly four times as concentrated as a 1:1 extract. While the concentration of an extract isn’t the only factor that determines its efficacy, it’s an important one. All other things being equal, we’d expect a 4:1 extract of Ginkgo to be more effective than a 1:1 extract. Ginkgo potentiates the action of other nootropics because it increases blood flow in the brain. The blood carries everything the brain needs to function optimally, including oxygen, glucose, lipids, micronutrients, amino acids, etc. So it’s no surprise that studies have shown that stacking Ginkgo with DHA, phosphatidylserine, folate, and B12 can have a synergistic effect. The recommended dose for Ginkgo is 120 to 240 milligrams per day. The lower dose can be used when Ginkgo is in a formula with other ingredients and/or with mild or moderate complaints, and a higher dose is typical for standalone use, and/or in people with dementia, Alzheimer’s [disease] or significant neurodegenerative conditions.
A really important thing to remember with Ginkgo, as I’ve mentioned a couple of times now, is that it can take several months to have its maximum benefit. This is not a supplement that you can take for a couple of days and notice a big difference with, and in fact, the benefits will continue to accrue over many months– up to 10 months in the one study we talked about. So I recommend taking it for at least three months before determining if it will really help you. As we discuss[ed], several studies showed significant benefits after just four weeks, so it’s not like you wouldn’t see anyimprovements during that time. But those improvements should accumulate over greater periods of time.

Alpinia galanga
All right, let’s talk about Alpinia galanga. I’m guessing this is one of the nootropics on this list you probably haven’t heard of, although you certainly have eaten it if you’ve had Thai food, because Alpinia galanga is a plant in the ginger family also known as Thai ginger, and it’s used as a culinary spice and in traditional medicine. It’s a perennial herb that may grow up to six feet tall in parts of India, Southeast Asia, and China, and it can be eaten fresh or cooked. It’s frequently used in Chinese, Indonesian, Malaysian, and Thai food. It’s [also] been used as a medicinal in Ayurvedic and traditional Chinese medicine for centuries. While it’s a newer kid on the block than some of the other nootropics we’ve discussed and research is ongoing, it’s already shown some fantastic benefits for brain health, cognitive function, and mood. Anecdotally, I can say that Alpinia can have a really, really nice effect on some people, leading to almost a mild euphoria accompanied by heightened focus, clear thinking, and greater creativity. I happen to be one of those people, so I’m a big fan of it. It’s probably one of my favorite nootropics, if not my favorite. And I’ve heard a few other people say that they feel it’s reminiscent of some of the best qualities of psychedelics but on a much milder scale and without any visual changes or challenging aspects of some psychedelic medicines. As we discuss Alpinia, I’ll be referring to a specific, patented ingredient called enXtra. This is a proprietary extract that targets a cognitive process known as attention network function, or ANF, which is the ability of the brain to allocate processing resources to a specific task. The ANF system plays a critical role in mental alertness and task focus. EnXtra interacts with dopamine and acetylcholinesterase to increase alertness and focus and elevate mood. One way to think about it is as a caffeine-free energy and mental clarity supplement, although it has many other benefits we’ll discuss. It has similar effects to coffee, tea, and other caffeine-containing substances, but without the jitters and other side effects.
Here are some of the other benefits of Alpinia, and enXtra specifically. It enhances cognitive performance. Studies in rodents found that extracts of Alpinia improved performance on tests of memory and learning, which may be due to its antioxidant and acetylcholinesterase inhibiting properties. It protects the health of brain cells. Compounds in Alpinia have demonstrated neuroprotective effects in cellular models by reducing oxidative stress and apoptosis. It boosts serotonin levels. One study showed that it increased serotonin levels in the frontal cortex of rodents [as well as in] the hippocampus, suggesting anti-anxiety and mood-lifting capabilities. Alpinia is anti-inflammatory. It inhibits pro-inflammatory mediators in the brain, which may promote cognitive function and emotional well-being. And finally, it has analgesic properties. This might be in part responsible for the euphoric effects that some people report with it. Compounds in Alpinia bind to opioid receptors and may have central analgesic effects, based on animal models of pain. This is another mechanism by which Alpinia can improve mood.
So let’s talk about a few studies. One study of Alpinia showed that it increased alertness and decreased fatigue in a randomized, double-blind, placebo-controlled crossover study. EnXtra supplementation improved alertness, reaction time, and correct responses to questions. Fatigue scores, which were measured five to six hours after supplementation, were reduced versus baseline in placebo. Another study showed that Alpinia increased alertness up to five hours after ingestion. This was a double-blind, placebo-controlled study of enXtra, and it increased the baseline alertness score up to five hours after taking it compared to several other plant extracts. It increases mental alertness and sustained attention versus caffeine. [In] another randomized, double-blind, placebo-controlled crossover study, enXtra increased mental alertness and sustained attention. They compared it to [both] caffeine and placebo, and the results demonstrated that enXtra supported mental alertness without any of the side effects of caffeine like increased blood pressure and heart rate. Lastly, it’s been shown to improve focused attention. This was a secondary analysis of another RCT, and it showed that enXtra improved focused attention, in this case to a greater extent compared to caffeine, and certainly to placebo, without any of the jitteriness or side effects.
So, there are different forms of Alpinia galanga out on the market. As I mentioned, I prefer the enXtra ingredient. It’s a DNA-authenticated extract, it’s natural, clean, gluten-free, non-GMO, and it’s supported by several peer-reviewed clinical studies. EnXtra is one of the nootropics on this list that does tend to produce an immediate effect for some people, although not everyone. Changes in alertness are typically seen within 30 minutes of ingestion, and it has been shown to provide up to five hours of sustained energy and focus without the crash of caffeine. That said, if you tolerate caffeine well, enXtra can stack very well with caffeine, along with many of the other nootropics that we’ve discussed. Again, we’ll talk a little bit more about that in a minute. Unlike caffeine, enXtra has no impact on heart rate, blood pressure, [or] sleep, even at two to four times the recommended dose.
So in terms of stacking, beyond caffeine there’s very little information in the peer-reviewed scientific literature about this because Alpinia is a relatively new nootropic. But anecdotally, both through my own personal use and in my work with patients, I found that it combines very well with Ginkgo, citicoline/UMP, and Bacopa. The recommended dose of enXtra is 150 to 300 milligrams per day. Once again, lower dose is typical when enXtra is combined with other ingredients and the higher dose is for standalone use. That said, in my experience, most people don’t see significant additional benefits beyond 150 milligrams a day. That seems to be a sweet spot for many. There’s definitely some individual variation here, but that’s been my experience so far.
Lion’s Mane Mushroom
Okay, last but certainly not least, we’re going to talk about lion’s mane mushroom. Lion’s mane, which is known as Hericium erinaceus, is an edible medicinal mushroom native to North America, Europe, and Asia. It’s one of the most beautiful edible mushrooms, I think, with cascading white tendrils that resemble a lion’s mane, hence the name. It has a long history of use in traditional Eastern medicine and cuisine. Lion’s mane is a delicious mushroom to eat if you like mushrooms, and that’s not always true of mushrooms like Reishi, for example. Cordyceps [and] chaga are [also] not very nice to eat, but lion’s mane is. It possesses several bioactive compounds that have been used in traditional Chinese medicine to support digestion, vitality, and cognitive health in the elderly. Modern research has confirmed these benefits and extended our understanding of its neuroprotective and neurotrophic qualities. In fact, it’s often referred to as the “smart mushroom” for its ability to improve cognition, memory, and to work as an antidepressant. Over the last 20 years, several in vitro and rodent studies have demonstrated lion’s mane’s efficacy and stimulating nerve growth factor. This is a game changer for brain and cognitive health, because until relatively recently, scientists believed the brain couldn’t grow new brain cells after childhood. Once we became an adult, we’d have [all] the brain cells we’d ever have in our life and we’d begin to gradually lose [them] as we aged. We now know that neurons can regenerate. But this often doesn’t happen. Several aspects of the modern lifestyle deplete nerve growth factor, and this leads to a decrease in long-term potentiation, death of brain cells, a decline in neuroplasticity, and a decrease in neurotransmitter production, all of which cause telltale signs of aging and cognitive decline.
Lion’s mane’s rare ability to stimulate nerve growth factor, or NGF, means it can potentially reverse this process of neurodegeneration as we age and even regenerate new brain cells and new connections between existing brain cells. Hericenones and erinacines are thought to be the two main categories of active compounds in lion’s mane. They are both unique to lion’s mane mushrooms and can both easily cross the blood-brain barrier. Hericenones stimulate nerve growth factor synthesis and secretion in cells by activating the synthesis and release of NGF from astrocytes, a type of glial cell that plays a variety of crucial roles in the brain. By increasing NGF, hericenones can reduce neurological decline, improve cognitive function, and stimulate new neuron growth. Erinacines are terpenoid compounds that powerfully stimulate NGF synthesis by activating gene expression in astrocytes. Erinacine A has also been shown to reduce myelin damage and stimulate myelin sheath regeneration in rats. Myelin protects neuron axons and is critical for proper nerve signaling. Lion’s mane also contains beta-glucoxylan and four other polysaccharides and polypeptides that significantly enhance immune function and decrease tumor growth. It’s being actively studied as a cancer therapeutic for this reason. Lion’s mane’s distinct ability to stimulate NGF leads to several brain health benefits. It reduces mild cognitive impairment and improves memory attention, executive function, and verbal comprehension. It elevates mood due to its ability to stimulate neurogenesis, the growth of new neurons. New neurons in the hippocampus specifically have been shown integral to reducing anxiety and improving depressive symptoms. It protects neurons and promotes repair after injury. It also reduces inflammation and oxidative damage in the brain. This suggests a protective effect with neurodegenerative diseases like Alzheimer’s [disease] and Parkinson’s [disease]. And finally, it may reduce amyloid plaques which block signals between neurons and are a defining feature of Alzheimer’s [disease[ and other neurodegenerative conditions.
Okay, let’s look at a few selected studies. A 2023 review found that lion’s mane had both neurotrophic and neuroprotective effects. It stimulated the production of NGF and brain-derived neurotrophic factor, or BDNF, supports brain cell growth, prevents brain cell death, reduces oxidative stress and inflammation in the brain, protects brain cells from hypoxia (low oxygen) and lack of blood flow, and is useful in both the prevention and treatment of neurodegenerative disease. Lion’s mane has been shown to improve cognitive function, memory, and quality of life in people with dementia, Alzheimer’s [disease] and impaired cognition. This came from a 2022 review called “The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease”. This is an alternative name for lion’s mane sometimes used in China. They call it the monkey head mushroom. This was a review of a bunch of different studies that found that lion’s mane offers many benefits for people with Alzheimer’s [disease]. This is a hugely important finding because there are currently no medications that significantly improve symptoms in people with these conditions. A 2020 paper indicated several potential benefits of lion’s mane for alleviating depression [and] improving mood. Hericenones have anti-inflammatory effects, and inflammation is now considered a primary driver of depression. Several studies have shown that lion’s mane reduces anxiety and depression in animal models, and several human clinical trials have replicated these effects suggesting that lion’s mane relieves depression, anxiety, frustration, palpitations, and insomnia in humans.
Finally, I’ve talked at length about the importance of the gut-brain axis on this show and on my blog. We now know that the gut and brain communicate in a bi-directional fashion and pathologies in the gut, like a disrupted microbiome and intestinal permeability, are driving factors for neurodegenerative conditions like dementia, Alzheimer’s [disease] and Parkinson’s [disease], as well as behavioral and mood issues like depression, anxiety, ADHD, and autism spectrum disorders. Lion’s mane has been shown to protect and repair the gut barrier, nourish the gut microbiome, reduce gut inflammation, and support the gut-brain axis in numerous other ways. Anecdotally, I’ve seen some remarkable results using lion’s mane with patients suffering from neurodegenerative conditions. In one especially memorable case, a 71-year-old male and his wife came to see me. He had recently experienced a rapid and alarming decline in cognitive function. He was often confused, disoriented, and slow to process speech. He’d been a mechanic most of his life and took pride in being able to assemble and build things, but he found himself unable to assemble even a simple dollhouse they’d bought their granddaughter for Christmas. After treatment with lion’s mane and some dietary changes, he recovered nearly 100 percent of his cognitive function. It was almost hard to believe. I mean, I’ve seen some pretty miraculous things in my time, but the change that I observed here was almost magic. And this was confirmed when he ran out of lion’s mane while traveling and experienced a significant regression, despite continuing with the dietary changes. Of course, individual responses will vary. It’s not going to be like this for every person, but I’ve used it with many different patients and almost always the response is very positive.
You have to be very careful when sourcing mushrooms like lion’s mane. As the popularity of mushrooms as supplements has grown, so has the proliferation of cheap, poor quality products. What’s more, most mushroom products on the market don’t actually contain mushrooms–the fruiting body stage of the fungal life cycle you think of when you picture a mushroom in your head. They contain mycelium, the threadlike vegetative part of the fungus that gives rise to the fruiting body. While mycelium certainly does have some health benefits, the vast majority of modern clinical studies demonstrating the benefits of mushrooms have used fruiting bodies, not mycelium. And fruiting bodies are what have been used for over 5000 years in traditional Chinese medicine as well. Most lion’s mane is mycelium grown on grain, and this will tend to have lower levels of beta-glucan and other active components like hericenones, and high levels of starch. It’s also important to choose mushrooms that are organic, given the potential for adulteration with pesticides and other chemicals.
In terms of stacking, lion’s mane is most often stacked with other mushrooms. This is what I did when I formulated Bio-Avail Myco for Adapt Naturals. It contains 225 milligrams of 100 percent organic lion’s mane fruiting body mushroom, along with seven other mushrooms– reishi, chaga, cordyceps, turkey tail, maitake, shiitake and tremella. But it can also be stacked with other nootropics that complement and extend its benefits, like Ginkgo, choline/UMP, phosphatidylserine, and Bacopa. The dose of lion’s mane can range from as little as 200 milligrams per day when used in a formula with other nootropics to as high as 3000 milligrams per day, or three grams per day, when used alone. The higher doses are often used by people with neurodegenerative conditions like Alzheimer’s [disease] and Parkinson’s [disease]. But it’s not always that simple. Some studies have shown that lower doses are more effective for stimulating nerve growth factor. I generally recommend a dose of 200 to 500 milligrams per day for people seeking improvements in cognitive function, mood, creativity, focus, and mental performance. For those struggling with significant signs and symptoms of cognitive decline, you can try a dose of 1000 to 1500 milligrams per day, and that can be increased to 3000 milligrams per day in the more severe cases of dementia, Alzheimer’s [disease], Parkinson’s [disease] or other neurodegenerative disorders.
How To Take Nootropics and Caffeine
Okay, whew, that was a lot. Hope you’re still with me. I’m just going to make a few general comments about how to take nootropics and their relationship with caffeine, and then we’ll wrap it up. Most of the nootropics we’ve discussed can be taken with or without food. Bacopa is fat soluble, so it’s best taken with a meal that contains fat or with a small amount of MCT or coconut oil if you take it in a fasted state. That said, if you’re taking a blend or a formula with several different nootropics in it, you can experiment with how you take it. Some people find that taking nootropics on an empty stomach, with or without caffeine, produces more notable immediate or short-term effects. Others may find that taking nootropics on an empty stomach can lead to nausea or other [gastrointestinal] (GI) discomfort and they do better taking them with food. There’s no hard and fast rule here. Trial and error usually reveals what works best.
Caffeine is another highly individual consideration. If you do well with it and it doesn’t make you jittery or cause sleep disturbances, I definitely suggest experimenting with stacking caffeine with the nootropics we’ve talked about today. Caffeine has a pronounced immediate effect but less of a long-term effect. Most of the compounds I’ve covered today can produce short-term changes, but they’re better known for intermediate- and longer-term benefits because they address underlying mechanisms and root causes. Caffeine pairs well with them because it produces complimentary effects. But if you are sensitive to caffeine, these nootropics can be excellent alternatives that offer many of the same benefits that people seek from caffeine, including improved alertness, focus, mental clarity, motivation, and mood.
In terms of dosage, I’ve tried to provide guidance throughout the show, so you can go back and listen to that or look at the transcript. But I will note that some trial and error and experimentation can pay dividends here as well. Some people will be naturally more sensitive to the effects of these compounds and they will do better with a lower dose. Other people will be less sensitive and require a higher dose to achieve the same benefits. You can experiment with taking one dose in the morning, or you can experiment with taking divided doses throughout the day. You can try taking it a half-hour or an hour before you have some kind of event that requires heightened alertness and focus, or mental or physical performance. As I mentioned, many of these compounds have benefits for physical activity and exercise and athletic performance. Let’s say you have a game or a match coming up, you could try taking it an hour before or a half-hour before. There are lots of different possibilities. Some experimentation is generally a good idea to find out what works best. And finally, just a reminder that most nootropics have synergistic effects when they’re stacked with other compounds. This is a phenomenon where one plus one equals more than two. You get these synergistic effects that you don’t get by taking each of them individually. That’s why I typically recommend taking several nootropics in a formula or blend, or at least stacking individual nootropics together. That almost always will produce better results.
Okay, I think that’s it– it was a lot. I hope this was helpful and introduced you to some new nootropics you weren’t already aware of, or maybe gave you some more information about ones that you’ve heard of but didn’t know much about. These compounds can make an enormous difference in mental clarity, brain health, mood, and quality of life in both healthy people and those struggling with brain fog, cognitive decline, behavioral and mood disorders, and more. Stay tuned for an exciting announcement next week related to what we’ve covered in the show today. It’s something I’ve been researching, developing, and testing for over two years, and I think you’re going to love it.
All right, that’s it for now. As always, you can view the transcript and scientific references for each episode on my website. Go to ChrisKresser.com and click on ‘podcasts’ and ‘navigation’. Keep sending your questions to ChrisKresser.com/podcastquestion. And in fact, this episode was originally born from a question we received about nootropics and which ones I like and recommend. So even though I’m not doing [the] Q&A format very often at this point, I still look at the questions and they inform the topics that I choose to interview guests on or do these solo episodes on. All right, that’s it. We’ll see you next time.

This episode of Revolution Health Radio is sponsored by LMNT.
As a member of our community, LMNT has a very special offer for you. Get a free LMNT Recharge Sample Pack when you purchase any LMNT product at DrinkLMNT.com/Kresser.

 

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Join the Writers Rising Retreat – with Anne Lamott, Cheryl Strayed...

If you’re a fellow or aspiring writer, today’s post is for you! The people behind the Writer’s Room have organized a pretty amazing retreat that...