Since a landmark study in 1998 (1), we have known that the brain can grow new brain cells to fix damage or boost cognitive function. Neurogenesis, the growth of new brain cells, is now understood to be a process associated with maintaining memory and cognition, and one that only functions in certain brain areas and under certain conditions.
The body of neurogenesis research has continued to accumulate, and clear mental benefits have been associated with it. For people who want their brains to perform at their peak, finding ways to increase neurogenesis is one great way to do that.
Neurogenesis: Growing New Brain Cells
Growing your brain means new neurons (brain cells) must be developed, moved into position, and integrated into the existing brain circuitry (2). This process is called neurogenesis, and it depends on the presence of stem cells, which are template cells that have the ability to turn into mature cells down the line.
Stem cells have the ability to turn into different cell types depending on the chemical signals they receive during development. The signals come from elsewhere in the body via signaling pathways or directly from cells next door to them. Neuronal stem cells are no different – they depend on a complex variety of signals to regulate their development, and understanding them is key to boosting brain growth (3).
Regulation is essential for neurogenesis. While neural stem cells are found throughout the brain, the process only takes place in two regions: the hippocampus, which is important for learning and memory, and the lateral ventricles, whose neurons contribute to the sense of smell (4).
Several nootropics can release natural chemicals that promote neurogenesis. This is one of the key ways they can help grow your brain.
Benefits Of Neurogenesis
Several lines of evidence have linked increased neurogenesis in the hippocampus to increased cognitive function and mood.
Being in an environment with positive stimuli is a natural way to boost neurogenesis (5). One study showed that mice whose hippocampal neurogenesis was increased by putting them in such an environment performed better than other mice in a memory test involving a maze (6).
Meanwhile, a genetically deficient strain of mice with a hippocampal neurogenesis rate 75% lower than regular mice performed significantly worse at memory and recognition tasks (7).
Neurogenesis could also affect mood regulation. This was first suggested by researchers who noticed that stress hormones, which are considered to be major contributors to anxiety and depression disorders, inhibited neurogenesis in the hippocampus (8).
This finding is supported by numerous studies that found that neurogenesis increased in depressed animals when they were given antidepressant treatments like fluoxetine (9).
Further evidence for the benefits of neurogenesis comes from observation of the elderly. Advanced age has been associated with reduced neurogenesis in the hippocampus (10), which is one reason why brain functions slow down as a person gets older.
Nootropics which are neurodegenerative can help people to keep growing and restoring their brain as they get older, or can help people who are chronically stressed, like those who suffer from anxiety disorders, to keep healthy patterns of neurogenesis and reap all of its benefits.
One of the most important classes of molecules regulating neuronal development are neurotrophins. They are a class of growth factors – proteins secreted to control the development and specialization of growing cells in a certain tissue type.
The neurotrophins are known to control neuronal development in a complex manner. They control the proliferation of neural stem cells, their migration to different locations, and their development into mature cells. After maturity, many neurons’ ongoing survival is also regulated by neurotrophins (11).
One study showed that the application of NT-3, a neurotrophin, could increase the proliferation of neural stem cells in cell culture in vitro. Then, they showed the same effect in vivo using mouse models (12).
This is the first step of neurogenesis. The proliferation of a healthy pool of stem cells ensures that there are sufficient template cells for the brain to work with.
Fibroblast Growth Factor 2 (FGF2), is another neurotrophin critical to the proliferation step. In studies using mice deficient for the gene which produces FGF2, neurogenesis was significantly decreased, a fact which resulted in impairment of their performance in memory-based tasks (13)
Elsewhere, researchers were able to induce the differentiation of hippocampal cells in culture by adding Brain-Derived Neurotrophic Factor (BDNF), NT-3, and NT-4 (14). This is the development step that turns non-functional stem cells into functional neurons.
BDNF also plays a crucial role in brain cell survival. A lot of our bodies’ cells depend on constant chemical signals to survive. When they stop receiving the signal, they begin to die. BDNF plays this role in many areas of the brain. One study of cells in the dorsal root ganglion of the brain used RNA to chemically block the expression of the BDNF protein by 80%. As a result, cell death increased by 35% (15).
Increasing Neurotrophin Production
Several nootropics exist which boost the body’s native production of neurotrophins. Most effective compounds for boosting brain growth work by boosting either BDNF or Nerve Growth Factor (NGF).
Lion’s Mane Mushrooms
Lion’s Mane mushrooms contain chemicals that boost the production of NGF. Researchers were able to isolate these novel compounds and characterize their mode of action, establishing the scientific basis to this natural medicine that has been used for centuries (16, 17).
Numerous other nootropics directly increase BDNF. These include L-Theanine (18), Bacopa monneri (19), and omega-3 fatty acids (20). Omega-3 fatty acids are a natural component of the diet found in fish, nuts, and seeds, but all three of these are available in nootropic extracts as well.
Ashwagandha is a plant native to the Indian subcontinent that has been used in Ayurvedic medicine for centuries. It promotes healthy brain activity, largely by boosting BDNF (21). It is an ideal nootropic because of its broad spectrum of related effects – we’ll be talking more about it later.
Neuronal growth is also stimulated by the colorful plant pigments called flavonoids. They are well known as strong antioxidants, but their beneficial action in the brain could not be explained by antioxidant activity – the concentrations of flavonoids in brain cells was too low (22).
It was later discovered that they had neurodegenerative effects too. Flavonoids can stimulate a major signaling pathway known as CREB, which in turn releases different neurotrophins, including BDNF (23).
In fact, many cultures have been using plants containing flavonoids for years as traditional treatments for anxiety, depression, and a wealth of other conditions. The Chinese use a plant called Xiao Bu Xin-Tang for this purpose for centuries. Researchers have recently proven that the flavonoids extracted from this plant significantly increased hippocampal neurogenesis in rats when administered orally (24).
Blueberries are another natural source of flavonoids. In a study measuring the memory-forming ability of rats navigating a maze, researchers measured levels of CREB in the brains and observed that rats on the blueberry diet had more than twice the concentration of the molecule. This coincided with a significant improvement in working memory in this group, showing a clear link between CREB activity and improvements in brain activity (25).
As well as blueberries and other food sources, extracts from the bark of the European maritime pine contain high concentrations of flavonoids, making it a good brain-boosting nootropic (26).
Providing Raw Materials For Neurogenesis
Regulation is one thing, but to construct new cells, the body needs a supply of raw molecular materials to build them out of. In particular, cells need phospholipids to construct their outer membranes.
Citicoline is an intermediate in the synthetic pathway that produces membrane phospholipids out of simpler building blocks. Taken orally as a supplement, it has a myriad of positive effects. Almost all of it is used by the body to produce phospholipids, especially a kind called phosphatidylcholine, which is used in central nervous system cells – like neurons (27).
Citicoline has been proven to protect neurons at all stages of the growth cycle. By enhancing the production of cell membranes, it stimulates neurogenesis and prolongs the lifespan of neurons.
It promotes the release of helpful neurotransmitters like dopamine and epinephrine while inhibiting the release of potentially damaging ones like glutamate. Finally, it can stimulate energy production in the cellular mitochondria and decrease the incidence of harmful free radicals (28)
The sum of these effects can be called neuroprotective. Neuroprotective effects help preserve neurons, salvage their components when they break down and promote their swift usage to build new neurons (29).
A neuron saved is the same as a neuron created. Neuroprotective agents work additively with neurodegenerative ones, as they consolidate each other’s effects by operating to boost and maintain brain growth at different stages of the neurodegenerative cycle.
Phosphatidylserine (PS) is another important phospholipid for your brain cells. It is not just a building block – there is a growing body of research suggesting that phospholipids facilitate intracellular reactions, including the opening and closing of ion channels which constitute intercellular communications (30).
In other words, healthy levels of phosphatidylserine can actively help your neurons to communicate properly.
PS has an important neuroprotective signaling function. When neurons are damaged, it migrates to the outer membrane and is recognized by receptors which allow the cell to be digested and its parts recycled quickly (31). Without this process, the dead cell can stay in place, clogging up space while its components go unused.
These dead neurons can also become toxic to nearby cells by causing local inflammation. PS signaling triggers the release of anti-inflammatory compounds which treat these local hotspots at the same time as they signal for the cell to be recycled (32)
Given these facts, you might expect PS to be valuable as a nootropic. That is exactly right. Taken orally, PS supplements are readily bioavailable and cross the blood-brain barrier (33). Once there, they improve memory recall, cognition, and mood (34, 35).
These effects were more pronounced in the elderly and those with neurodegenerative diseases – people whose neurons are more vulnerable. A large-scale study of 492 elderly patients with symptoms of memory loss and cognitive impairment considered the effects of PS supplementation across a range of standard tests of cognition and recall. The PS group experienced a 13% increase in scores across the range of tests compared to the placebo group (36).
So far, we have discussed brain growth in the sense of creating new neurons that become integrated into existing pathways. We’ve also seen that the efficacy of these pathways in terms of speed and accuracy of communication between the pathway’s individual cells can be increased or decreased.
The brain also possesses the ability to reroute pathways or grow new ones entirely. This property is called neuroplasticity. A child’s brain is highly neuroplastic, forming new pathways constantly as they learn new things. The adult brain is less so but retains the ability to form new pathways in response to damage or learning new tasks (37).
Enhancing the neuroplasticity of your brain can lead to improvements in cognition and memory recall, much like with neurogenesis (38). Maintaining neuroplasticity is important for forming long-term memories (39).
Chronic stress can reduce neuroplasticity and cause the neurons in the hippocampus to start degenerating – the opposite of neurogenesis. This reduces your cognitive functions and can contribute to mental disorders like major depression (40)
Avoiding stress can be difficult in the modern world, but several nootropics can improve neuroplasticity in the adult brain, supporting brain growth and helping to nullify the detrimental effects of stress.
Citicoline is one. Because it facilitates the growth and recycling of neuronal materials, it can speed up the rerouting of neuronal pathways and stimulate their growth (41).
Ashwagandha is another. An extract from its roots was administered in a clinical trial to rats who were placed under conditions that promoted neurodegeneration. It proved to be effective in blocking the damage caused by stress hormones and oxidative damage (42).
Its effectiveness is also evident in human trials. A study of 64 adults who suffered from chronic stress found that after 60 days of supplementation with ashwagandha root extract, the patients had significant reductions in their serum cortisol levels and scored better on all stress-assessment scales used in the study (43).
Another study on healthy volunteers showed the extract led to a significant improvement in memory and cognitive functions compared to a control group (44).
The Correct Dosage
A common refrain for toxicologists is “the dose makes the poison”; how much of something you take is important for how it will work in your body. Many compounds with neurodegenerative properties only work at certain concentrations.
Researchers investigating the neurodegenerative properties of curcumin, which occurs naturally in curry spices, found that low concentrations caused neural progenitor cells to proliferate. When the concentration became too high, it caused cells to die (45).
Take Ashwagandha supplements. In safety tests, researchers found that the extract of this plant was safe to take with minimal side effects, even at high doses. But, at these high doses, mild symptoms like nausea and stomach pain did occur in some subjects (46).
With extracts in the form of supplements, you always know the exact dosage. This allows you greater control compared to consuming these plants in other ways.
That being said, supplements should always complement a healthy lifestyle. Aerobic exercise, healthy sleep patterns, and a good diet will boost your brain growth as much as any supplement can – it’s when you put the two together that you can achieve the greatest benefits.
‘Brain growth’ is a tough concept to pin down. It can refer to neurogenesis itself – the creation of new neurons and their integration into the existing circuitry. It also encompasses changes in how efficiently the neurons in these pathways function and even how well neurons can reorganize themselves into new pathways (neuroplasticity).
This system is regulated at various different stages within the process. So, nootropics have a lot of targets at which to act. The best nootropics for brain growth are broad-spectrum – they contain multiple compounds which act in different ways, leading to greater effects.
Ashwagandha, citicoline, and maritime pine bark extract are a few of the nootropic supplements that boost brain growth. Lifestyle changes can also have an impact, so it’s a good idea to start with achieving a healthy diet and regular exercise.
When you combine a healthy lifestyle with nootropic supplements, you’ll find yourself in the best position to achieve long-lasting gains in brain growth throughout your lifetime.