Have you ever wondered if it would be possible to hack your way to an enhanced state of awareness and improved memory, cognition, and concentration with a single pill? While an exact replica of the Limitless pill may not exist, there are compounds recognized for their ability to alter cognition for the better. Side note: we intentionally include only substances whose efficacy has been scientifically proven. A host of compounds boasting brain-enhancing claims (but which may also not have been subject to rigorous safety and efficacy studies or are known to have significant safety issues) are widely available for purchase; these products, which include Aniracetam, Modafinil, Centrophenoxine, and Sulbutiamine, are left out of this discussion and are best left avoided.
Vitamin D – Vitamin D has been implicated in a wide variety of physiological functions, spanning the endocrine, immune, and skeletal systems. Although less studied, vitamin D is thought to play a significant role in cognitive function, as well. Receptors for vitamin D have been identified throughout the central nervous system and in the hippocampus, the area of the brain involved in memory formation/consolidation and spatial recognition. In these areas, vitamin D plays a protective and regulatory function, controlling production of enzymes involved in neurotransmitter synthesis and nerve growth.
Recent psycho-neurological studies have linked lower blood vitamin D levels to poorer performance on mental tests and an impaired ability to process information, with this effect magnified in those over 60 years of age.
It is worth noting that vitamin D is a fat-soluble vitamin and is best absorbed when taken with fatty foods. For best cognitive enhancement, take vitamin D with a few teaspoons of cod liver oil or a serving of fish oil, with beef or butter, or calf’s liver (this shouldn’t be consumed too frequently, however). Vitamin D dose can range from 2000 – 4000 IU, and should preferably come from a highly absorbable liquid source, such as a spray or oil.
Vitamin K2 – The brain is one of the most concentrated sources of vitamin K2 in the entire body. There, the fat-soluble vitamin acts as an antioxidant, helping to prevent free radical-mediated damage and contributes to the production the myelin sheath, the protective covering surrounding the axonal bodies of all neurons. The myelin sheath acts as an insulating material, helping propel signal transduction and neuronal communication.
Vitamin K exists as a number of naturally occurring vitamers, the most prominent of which are vitamins K1 and K2. Vitamin K1 (phylloquinone) is synthesized in plants and is the predominant form of the vitamin in the human diet. Vitamin K2 (family of menaquinones) are largely synthesized by human intestinal microbiota, but can also be found in fermented products (e.g., kefir, natto) and animal products. Unless you are vegan/vegetarian or have serious vitamin K deficiency, obtaining adequate amounts of vitamin K through natural sources is recommended over supplementation. Among the benefits of natural sources of vitamin K2 is that they often contains fats, which aid in the absorption of fat-soluble vitamin K.
Fatty Acids – Arachidonic acid, a polyunsaturated omega-6 fatty acid found in abundance in the brain, helps build and stabilize cell membranes in the hippocampus (part of the brain involved in information consolidation and spatial orientation), helps prevent free-radical mediated damage, and helps neuronal growth and repair. In one study, 18 month-old infants who supplemented with arachidonic acid showed significant improvement in cognitive ability and intelligence. In adults, impaired metabolism of arachidonic acid or insufficient intake has been linked to cognitive decline, bipolar disorder, and degenerative neurological disease such as Alzheimer’s Disease.
Arachidonic acid-rich foods include fish (tilapia, catfish, yellowtail, and mackerel), fatty cuts of meat, duck, eggs, and dairy. Additionally, it is important to note that adequate fat intake is essential for active women who plan on having children. Fat in the hip and buttocks are significant sources of essential omega-3 fatty acids and DHA, both of which are heavily involved in the brain development of the baby. It is thought that inadequate fat intake has the potential to compromise the baby’s intelligence.
Phosphatidylserine – Phosphatidylserine is a phospholipid (phosphorylated fatty acid) that serves as a major structural component of cell membranes, particularly in neural tissue. It has also been shown to increase levels of acetylcholine, one of the nervous system’s major neurotransmitters.
Phosphatidylserine has been shown to improve memory and spatial recognition in rats. It may have similar effects in humans, although the majority of studies have been conducted on elderly subjects (for whom phosphatidylserine has shown benefit against the progression of Alzheimer’s Disease and dementia).
Phosphatidylserine exists as a supplement, though it tends to fall on the more expensive side of the spectrum. Instead, it may be more biologically beneficial and money-savvy to get your phophatidylserine fill from natural sources, of which fish such as herring and mackerel are particularly rich.
Fish Oil – Thought, memory, and information processing are conceptual ideas rooted in physical, neurological processes: the electrochemical transmission of a “signal” down the axonal membrane, the release of neurotransmitters (the brain’s messengers), their travel across a synapse (the space between two nerve cells), and the stimulation of next neurons dendritic ends (which sends this electrochemical process into repeat). The release and uptake of neurotransmitters is heavily dependent on the health of the neuronal cell membrane, which is comprised of approximately 20% essential fatty acids like the omega-3’s found in fish oil.
Specifically, omega-3 fatty acids contribute to membrane elasticity, which increases the efficiency with which neurons are able to propagate electrochemical signals. Inadequate omega-3 intake may hinder signal propagation as well as the function of structures called G-Protein Coupled Receptors (GPCRs), which are essential components in the communication between neurons.
Up to 2g/day of omega-3 fatty acids (in either supplement of fish form) has been shown to reduce the severity of dyslexia and attention deficit hyperactivity disorder (ADHD), Alzheimer’s Disease, brain atrophy and cognitive decline. Aside from preventing cognitive decline, it has been shown to improve cognitive function in healthy individuals. It is best to pair a daily dose of 1-2 grams of triglyceride-based fish oil with cold-water fish such as mackerel, herring, anchovies or sardines. If supplementing, look for products containing antioxidants such as astaxanthin or vitamin D or E and to increase intake of dark, leafy vegetables and dark fruits.
Medium Chain Triglycerides (MCTs) – When fat is used as cellular fuel, one of the metabolites formed is acetyl-coenzyme A (acetyl-CoA), which becomes the body’s source of ketones, the brain’s preferred fuel source. It is suggested that cognitive function enhances (with faster information processing and sharpened focus) during ketosis, a condition characterized by elevated levels of ketones in the blood.
One of the most efficient ways to develop a mild state of ketosis is by consuming fats called medium chain triglycerides (MCTs). MCTs are unusual fats; typically, fats are broken down in the intestine and reassembled into a specialized form that can be absorbed into the blood. MCTs, on the other hand, are absorbed completely intact and are directly transported to the liver, where they are used for energy. Few natural sources are known to be rich in MCT content, although coconut oil is perhaps the best known. MCTs can also be purchased in a purified, concentrated form as liquid MCT oil.
MCTs have recently come into the national spotlight as part of the Bulletproof Coffee (TM) recipe, a coffee blend with butter and MCT oil that promises to enhance cognitive ability and energy. Blend a few tablespoons with coffee or simply eat a few tablespoons of coconut oil, preferably during the mornings or mid-afternoons. Word of caution: MCT oil can cause stomach upset, so start small and gradually increase doses.
Caffeine – 100mg of caffeine, approximately the amount in an 8 oz. cup of black coffee, has been shown to improve memory recall. Caffeine’s psychostimulatory effects stem its ability to prevent the binding and signaling of the (generally) inhibitory neurotransmitter adenosine. The result is an increase in dopamine and glutamate, two of the nervous system’s major feel-good, excitatory neurotransmitters.
Let me be clear – more caffeine is not necessarily better. More than 400 mg of caffeine daily–about the amount found in 4-5 cups of coffee–has been linked to a variety of cognitive and cardiovascular disorders. One of the more ironic side effects of excess caffeine intake is its ability to decrease blood flow to the brain, impairing function. It should also be noted that it is possible to build tolerance and become addicted to caffeine. In fact, the American Psychiatric Association recognizes at least three caffeine-based disorders: caffeine intoxication, caffeine-induced sleep disorder, and caffeine-induced anxiety disorder.
As a note, best effect is often achieved by consuming high quality, fresh coffee made from Arabica beans. Coffee powders and substitutes are thought to be higher in mycotoxin content, a fungus linked to impaired cognitive ability.
L-Theanine – L-theanine is one of the major amino acid components of green and black teas and is suggested to have anti-stress and anxiolytic effects. The basis of l-theanine’s action is to increase inhibitory activity in the brain; because it is a glutamate analog, it binds to receptors specific to glutamate, prevents their binding, and inhibits its excitatory action. It has also been shown to boost dopamine levels (the neurotransmitter involved in feelings of happiness associated with reward) and enhance alpha wave activity, brain waves indicative of a relaxed state.
L-phenylalanine – Outside of its role in protein synthesis, the amino acid L-phenylalanine also boasts significant cognitive-enhancing effects. It is the structural basis of our brain’s major attention- and focus-enhancing neurotransmitter, dopamine. The draw of L-phenylalanine as a nootropic is its ability to enhancing cognition without interfering with the hypothalamic-pituitary-adrenal (HPA) axis–a complex network of interactions between three endocrine glands that regulate a variety of bodily function, including reactions to stress, digestion, immunity, cognition, sexuality, and energy expenditure.
Creatine – Creatine not only boasts strength and power-enhancing effects, but is also being increasingly recognized for its nootropic benefits. Creatine may have a neuroprotective effect by slowing neuronal cell death and may also increase levels of glutamate, improve memory and learning, assist with depression, and suppress serotonin spikes.
This is particularly important to vegans and vegetarians, who may stave off the cognitive fuzz characteristic of a plant-based diet by consuming creatine with adequate amounts of dietary fat.
The majority of scientific study use a standard regimen for creatine supplementation: starting with a large loading dose to be maintained for ~1 week and followed by a smaller maintenance dose for the duration of the study. Typically, 0.3g/kg of body weight is used as a loading dose with 5g creatine daily used to maintain intake. However, if meat is consumed frequently, ~2g creatine daily is thought to be enough to maintain average creatine stores.
Carnitine – Carnitine is the structural precursor to acetylcholine and is recognized for its roles in the synthesis and stabilization of electrically-active membranes, regulation of neural genes and proteins, enhancing mitochondrial (cellular energy factory) function, mitigating free radical-mediated damage in the brain, and enhancing glucose uptake into the brain.
Carnitine has been shown to have a variety of other physiological effects that are rooted in slowing down signs of aging, including neurological decline and chronic fatigue, and improving insulin sensitivity and blood vessel health. It has also been linked to an increased ability to burn fat and enhanced mitochondrial respiration. In essence, the effects may lead to increased alertness and focus as well as increased energy–a particularly attractive option as a pre-workout regimen. 750-2000mg daily, split into two daily doses, is recommended.
Alpha-Lipoic Acid – Alpha-lipoic acid (ALA) is a fatty acid that has been shown to help prevent age-related neurological decline. Specifically, ALA may reduce oxidative damage in neuronal cells, increase the release (and concentration) of glutamate, and increase dopamine and acetylcholine availability. The general dosage for cognitive enhancement falls in the 300-600mg/daily range.
Huperzine – Huperzine is known as an acetylcholinesterase (an enzyme that breaks circulating acetylcholine) inhibitor, effectively increasing levels of acetylcholine in the nervous system. Studies have shown that huperzine has neuroprotective effects and can enhance cognitive function in both animals and humans. While the compound is widely available in supplement form, most people fail to realize that is also available in its natural form, an herb called Club Moss (which has been used to slow the progression of Alzheimer’s Disease in Ancient Chinese Medicine). Club moss is available in herb stores, although we encourage you to use caution when purchasing Chinese herbs. They have been known to sit in large bins for extended periods of time, to the point at which they become sufficiently aged and ineffective. To make matters worse, they are often sprayed with ethylene oxide, a compound linked to carcinogenic and mutagenic activity. Try to ascertain your product’s freshness, purity, and efficacy before committing to the purchase.