Folates are the natural form of vitamin B9, found in real foods, such as dark coloured leafy vegetables. — J HOWELL/Pexels
For many decades, the prevailing belief was that the number of cells in the adult human brain was static, incapable of producing new neurons after adulthood.
However, research has established that this is not true, at least in an important part of the brain called the hippocampus. Studies since the 1960s have established that several mammals can regenerate neurons in this region throughout their lives. There had since then been considerable research into the same phenomenon in human brains, with inconclusive outcomes. Finally, plausible evidence that adult human brains can also regenerate and renew hippocampal cells was collated in a detailed 2021 Spanish review, “Evidences for Adult Hippocampal Neurogenesis in Humans”.
Moreover, it appears that this process, known as “neurogenesis”, plays a crucial role in human learning, memory, and overall cognitive function throughout all our lives. While the generation of new neurons in the adult human hippocampus occurs at a significantly reduced rate compared to infancy and childhood, these nascent cells still play a critical role in maintaining mental well-being, underpinning the hippocampus’s vital function in memory consolidation and cognitive function.
Brain-friendly diet
It is no surprise to learn that the foods we consume can either enhance or hinder neurogenesis. Adopting informed dietary choices can empower our brains to function at their best and potentially stave off cognitive decline as we age. And these informed choices are often simple, delicious, and effective.
The best foods to promote neurogenesis are those which provide the chemical building blocks and support systems necessary for robust neurogenesis. Usefully, they are often also the most highly recommended foods to eat for optimal general health.
Omega-3 fatty acids
These healthy fats are abundant in oily fishes like salmon, mackerel, sardines, and also in certain algae, walnuts, flaxseeds, leafy greens, etc. Omega-3 plays a critical role in brain health by improving the fluidity of brain cell membranes, allowing for better communication between neurons. Importantly, they also boost the production of BDNF (Brain-Derived Neurotrophic Factor), a special protein essential for neuronal augmentation, survival, differentiation, morphogenesis (development of form and structure in cells), and synaptic plasticity (improved function and linkage stability).
Omega-3 fatty acids can be found in oily fish like salmon, which is critical for improving the fluidity of brain cell membranes. — Sebastian Coman Photography/Pexels
Omega-3 fatty acids are divided into short-chain and long-chain acids. The short-chain acid is known as Alpha-Linolenic Acid, contains 18 carbon atoms and is mostly found in seeds and plants. The long-chain versions are usually derived from oily fishes and includes Eicosapentaenoic Acid which contains 20 carbon atoms, and Docosahexaenoic Acid (DHA) which contains 22 carbon atoms.
Of particular interest to neurogenesis are the long-chain DHA molecules, which activate the expression of genes related to BDNF production. These genes then activate molecules such as the CREB (Cyclic-AMP Response Element-Binding) protein in the brain. The activation of CREB by BDNF not only supports neurogenesis but also enhances further BDNF expression itself, creating a positive feedback loop that reinforces neuronal growth and plasticity.
DHA also provokes other required signalling pathways required for BDNF production. DHA and other omega-3 acids then assist in regulating BDNF production in several interesting ways too complex to describe here; eg, via expressing complex paired protein structures called “heterodimers.”
Polyphenols
Found in a vibrant array of fruits and vegetables such as blueberries, strawberries, grapes, red onions, spinach, as well as olive oil, tea, cocoa, polyphenols are powerful molecules that protect brain cells from damage and help promote neurogenesis.
Polyphenols work in several ways, and probably the most well-known mechanism is the suppression of inflammation (or neuroinflammation in the brain), via their antioxidative properties. This confers a degree of protection against injuries from various toxins, derived either from bad diets or environmental factors. Reduced inflammation creates a much better environment for the development of new neurons.
Some lesser-known effects of polyphenols in the brain are:
• their ability to trigger signalling cascades in the brain, thus promoting neuronal survival and synaptic plasticity,
• enhancing the proliferation and differentiation of new cells in the subgranular and subventricular zones and the dentate gyrus of the hippocampus; and,
• inducing the expression of an unusual protein called “doublecortin,” specifically found only in developing neurons.
Vitamins B9 and B12
Essential for DNA synthesis in the body and the production of neurotransmitters, vitamins B9 and B12 are also crucial for neurogenesis. Leafy greens, beans, fish, and dairy products are examples of good sources of these vital nutrients.
There are two types of vitamin B9 available for human consumption: (1) folates, and (2) folic acid. While roughly equivalent in function, there are significant differences.
Blueberries and other ingredients like strawberries and red onions contain polyphenols which protect brain cells from damage. — Veeterzy/Pexels
Folates are the natural form of vitamin B9, found in real foods, such as dark coloured leafy vegetables, beans, seafoods, nuts, etc. They are easily destroyed by high cooking heat. Hence, they are seldom found in ultra-processed foods (UPF).
Folic acid is a synthetic compound usually manufactured via a chemical process involving para-nitrobenzoic acid, thionyl chloride, toluene, monosodium glutamate, etc. Despite its artificial origins, there are health benefits of folic acid, which are often added to UPFs such as baked goods, cereals, pastas, flours, etc. The inclusion of folic acid in such foods was mandated in 1998 in the USA to prevent neural tube defects (severe defects of the central nervous system) in newborn babies.
An advantage of folic acid is that it is significantly more bioavailable for absorption (85%) than folates (50%) and it is also less affected by cooking heat and food processing. However, folic acid must be converted into 5-methyltetrahydrofolate (5-MTHF) before it is usable by the body. Folates from real food are already in 5-MTHF form and importantly are also presented with special proteins called Carrier Food Factors (CFF), which direct 5-MTHF to various target organs in the body, including the brain. Folic acid has no such complementary proteins.
The effect of vitamin B9 on neurogenesis is simply dose dependent. A chronic shortfall of B9 induces degeneration of the brain while elevated levels promote neurogenesis.
Vitamin B12 is known for stabilising and repairing neurons in the brain. It does this by maintaining the myelin sheaths of the axons of brain cells. Axons are the fine long dendritic links used by neurons for communication with other neurons. The vitamin also promotes the production of the myelin needed for the axons of new brain cells during neurogenesis. Additionally, B12 induces antioxidant activity by stimulating the production of special enzymes which destroy free radicals.
Anti-inflammatory foods
Any foods that reduce inflammation in the body are likely to be good for neurogenesis. This is simply because neurogenesis is impaired by inflammation. Bad diets can introduce free radicals and other inflammatory molecules into the body, which can then migrate from the digestive system into the blood, and then into the brain.
The range of anti-inflammatory foods is extensive, and include berries, leafy greens, fatty fish, nuts, whole grains, olive oil, turmeric, green tea, dark chocolate, etc. Basically, if you eat mostly natural plant-based foods (especially colourful vegetables in their raw forms) and avoid red meats and processed foods, your diet would almost certainly be helping to reduce inflammation in your body.
Factors hindering neurogenesisMany factors can hinder neurogenesis. These factors are all around us and sometimes may be unavoidable.
Lousy diets
Ultra-processed foods (including junk and fast foods) are among the most harmful dietary choices for brain health. UPFs are cheap, delicious, ubiquitous, and can wreak havoc on brain health if over-consumed. Ingredients such as poor-quality fats (see below), processed starches, additives, sugars, and salt in UPFs reduce BDNF levels, impair neuroplasticity and induce neuroinflammation. Over-consumption of some UPFs has also been linked to cell deaths and cancers, which are the claimed side-effects of certain artificial additives.
Overconsumption
Lousy diets and UPFs frequently trigger intense food cravings by causing dramatic fluctuations in blood glucose levels. This is a consequence of their refined starches and elevated sugar concentrations. These glucose swings can lead to eating addictions/cravings and subsequent overconsumption. Persistent overconsumption of lousy foods normally leads to diseases linked to metabolic syndrome over time. And nothing about acquiring metabolic syndrome is conducive to neurogenesis.
Consuming copious amounts of ultra-processed foods like store-bought doughnuts has been linked to cell deaths. — MCCUTCHEON/Pexels
Poor-quality fats
We are generally aware of the dangers of over-eating saturated animal fats, because of their impact on blood cholesterol levels. But there is another danger of over-consuming certain plant-based fats, which is much less known.
The ratio of Omega-3 and Omega-6 fatty acids for humans should ideally be around 1:2, as it was during Palaeolithic times. However, a modern Western diet has an average ratio of 1:15. This high ratio is largely attributable to the amounts of Omega-6 fatty acids in processed foods and seed oils, while the amounts of dietary Omega-3 fatty acids have remained relatively static. Note that some UPFs have unhealthy ratios of 1:30 or more, as producing foods with Omega-6 oils is much cheaper than using Omega-3 oils.
A consistently overly high ratio of Omega-6 in the diet is potentially a significant issue. Omega-3 metabolises into anti-inflammatory compounds while Omega-6 is processed into pro-inflammatory molecules. However, both are metabolised by the same enzymes (delta-6-desaturase and delta-5-desaturase). Therefore, there is competition for these enzymes during digestion.
Higher amounts of Omega-6 would grab more of the enzymes, resulting in the production of more pro-inflammatory signalling molecules (eg, eicosanoids, prostaglandins, and leukotrienes). Without Omega-3 to mitigate Omega-6, large numbers of pro-inflammatory molecules can trigger a cascade of inflammation throughout the body and brain via complex processes too detailed to describe here.
This is a two-part column. The next part explores the enigma of red wine and offers other factors which can promote neurogenesis.
The views expressed here are entirely the writer’s own.
