What are Nootropics?
Nootropics are a hot topic these days – herbs and supplements taken for improving cognitive function. In order to be classified as a nootropic, the constituent or herbal substance must improve the ability of the brain to function in one way or another. There are also synthetic compounds used as nootropics though they are not discussed in this article. Nootropics have long been popular for age related cognitive decline but in today’s world of fast-paced, competitive jobs many young professionals and students are also interested in optimizing cognition and creativity. Nootropics come in a variety of botanical and supplemental formats. Whole plant extracts, single constituent extracts and even single compounds isolated from plants and fungi. Here I discuss a few examples that I work with.
The general actions of which nootropics can be organized in several areas:
· increasing cerebral blood flow
· having direct impact on acetylcholine receptors or enzymes breaking down acetylcholine (like racetam drugs)
· neurotransmitter modulation such as dopamine, glutamine, GABA, glutamate, serotonin;
· being building blocks of acetylcholine, phospholipids or catecholamines (dopamine, epinephrine, norepinephrine)
· to enhance nerve membranes and thus enhance nerve conduction
· to facilitate low-level neuroplasticity and growth
Before adding in any supportive product to your routine, first ensure that the fundamentals of health are in place for you. If any of these are lacking or inadequate then attempting to enhance cognitive function will not be a sustainable target. The fundamentals of health that must be in place are adequate sleep, proper diet, hydration, movement and exercise, and social support and interaction.
As a naturopathic doctor I provide medical advice to patients, however unless you are actively a patient of mine I cannot say that any of the below substances are safe or appropriate for your use. Please consult a naturopathic physician or another health professional trained in the interaction of pharmaceuticals, health conditions and health products before starting a new product.
Phosphatidylserine
Phosphatidylserine is a fat like substance that is naturally produced in the brain, lungs, testes, kidneys, liver, heart and blood plasma; it forms the lipid bilayer of the neural cell. It gets integreated into the cell membrane and contributes to cell fluidity, positively influences Na+/K+ATPsase activity and decreases acetylcholinesterase. Supplementation has been shown to increase cognitive function and memory especially in older populations. Natural phosphatidylserine levels have been shown to decline with age. Phosphatidylserine supplements are extracted from soy lecithin and krill oil; they can also be found in bovine sources however this is not recommended due to risk for contracting Creutzfeldt-Jakob disease. Daily dosage of 100-500 mg, taken in divided doses of 50-100 mg.
Omega 3 Fatty Acids
Omega 3 fatty acids are incorporated into the cellular phospholipid bilayers; docosahexaenoic acid (DHA), alone, accounts for 40% of the phospholipid content of nerve membranes. Eicosapentaenoic acid (EPA) also plays a central role in neurotransmitter function, signalling and synthesis as well as modulation of many inflammatory functions in and around the nervous system. Numerous studies have shown that increased dietary omega-3 intake is associated with better cognitive performance. Omega 3 fatty acids are relatively difficult to obtain from diet other than from cold water fish and some seed oils such as flax and borage. Supplementing with omega 3 fatty acids with 2 grams daily over a 24 week period was shown to significantly improve scores on a standardized assessment of cognitive function.
Alpha-GPC
Alpha-GPC is a naturally occurring choline compound that passes the BBB and provides choline for building neurotransmitter acetylcholine. Alone it is useful in the treatment and prevention of Alzheimer’s disease, which has been shown in double blind clinical trials as having significant benefit. However, the best cognitive enhancement occurs when alpha-GPC is in formula with other nootropics. It is best to think of alpha-GPC as an optimization agent which allows the other components (such as phosphatidylserine) to reach their full potential. It pairs well with acetylcholine up-regulators and provides additional benefit in maintenance of cell membranes by providing phospholipid components. Alpha-GPC is produced in small amounts in the human body, however from plant sources it is derived from soy, sunflower lecithin and milk. It is found to be one of the safest nootropics available. Dosages range from 60 to 1400 mg in divided doses, however best course of action is to start low at 60 mg per day and go up from there.
Huperzine-A
Huperzine-A is a naturally occurring nootropic agent that acts mostly on acetylecholine levels in the brain by inhibiting acetylcholinesterase. Huperzine-A comes from a genus of plants known as Huperzia. Other species in the genus also contain huperzine-A however it is most commonly sourced from the Chinese club moss – Huperzia serrata. It is an alkaloid that like other alkaloids has potential to cause dramatic changes in the body. Only a small amount of the alkaloid is needed for its cholinesterase inhibiting effect, therefore even whole plant extract of Huperzia serrata can be used in nootropic formulae. The effective dosage range is less than 1 mg and roughly 50-200 micrograms are all that is required to have therapeutic effects in the body. Huperzine-A is found to have little to no side effects overall, however some people report sensitivity to this nootropic. Personally I find it quite stimulating and think it best when combined with other nootropics that provide more of the nourishing building blocks for material as well as enhancement for blood circulation.
L-theanine
L-theanine is a well known amino acid commonly found in Camellia sinensis. It mimics neurotransmitters and induces a state of relaxed focus. It is incredibly useful as a nootropic by its ability to create a state of relaxed focus, particularly when in combination with stimulating nootropics such as caffeine and huperzine-A. By mimicking glutamate (the brain’s excitatory neurotransmitter) L-theanine is able to reduce its effects, effectively turning down the brains hyperactive state. The effect however is not truly sedative as there remains an alertness and focus when taken during the day, despite its ability to also reduce anxiety and shorten time taken to fall asleep. L-theanine is well known and used, optimal dosage range is 200-400 mg per day.
Gingko
Extracts of Ginkgo biloba have long been used in traditional Chinese medicine for various disorders. A standardized extract is widely prescribed and used in Europe for the treatment of age-related associated cognitive decline. Gingkolides from Gingko stimulate circulation to the brain and act as anti-inflammatories that help relieve oxidative stress. It has been shown to improve brain metabolism of glucose and oxygen, and the useage of acetylcholine. Promotes blood flow to the brain to promote memory and cognition, act as an anti-coagulant and anti-oxidant. Useful for age related cognitive decline that also has restricted blood flow and peripheral vascular disease as contributing factors. Daily dosage of standardized gingkolides to 250 mg once per day. As with all herbal medicine and supplements, you must consult with your doctor, a naturopathic physician or other qualified health provider to ensure that the supplement is right for you and won’t interfere with medication.
References:
hiu CC, Su KP, Cheng TC, et al. The effects of omega-3 fatty acids monotherapy in Alzheimer’s disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(6):1538-1544.
Gao Q, Niti M, Feng L, et al. Omega-3 polyunsaturated fatty acid supplements and cognitive decline: Singapore Longitudinal Aging Studies. J Nutr Health Aging. 2011;15(1):32-35.
Dangour AD, Allen E, Elbourne D, et al. Fish consumption and cognitive function among older people in the UK: baseline data from the OPAL study. J Nutr Health Aging. 2009;13(3):198-202.
Kim TI, Lee YK, Park SG, et al. l-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways. Free Radic Biol Med. 2009;47(11):1601-1610.
Alves E, Binienda Z, Carvalho F, et al. Acetyl-L-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain. Neuroscience. 2009;158(2):514-523.
Taglialatela G, Angelucci L, Ramacci MT, et al. Acetyl-L-carnitine enhances the response of PC12 cells to nerve growth factor. Brain Res Dev Brain Res. 1991;59(2):221-230.
Richter Y, Herzog Y, Cohen T, Steinhart Y. The effect of phosphatidylserine-containing omega-3 fatty acids on memory abilities in subjects with subjective memory complaints: a pilot study. Clin Interv Aging. 2010;5:313-316.
Kato-Kataoka A, Sakai M, Ebina R, et al. Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J Clin Biochem Nutr. 2010;47(3):246-255.
Vakhapova V, Cohen T, Richter Y, et al. Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial. Dement Geriatr Cogn Disord. 2010;29(5):467-474.
Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003120.
Mashayekh A, Pham DL, Yousem DM, et al. Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study. Neuroradiology. 2011;53(3):185-191.
Araujo JA, Landsberg GM, Milgram NW, Miolo A. Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine. Can Vet J. 2008;49(4):379-385.
Kennedy DO, Haskell CF, Mauri PL, Scholey AB. Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine. Hum Psychopharmacol. 2007;22(4):199-210.
ripanya N, Saparpakorn P, Wolschann P, Hannongbua S. Binding of huperzine A and galanthamine to acetylcholinesterase, based on ONIOM method. Nanomedicine. 2011;7(1):60-68.
Myers TM, Sun W, Saxena A, et al. Systemic administration of the potential countermeasure huperzine reversibly inhibits central and peripheral acetylcholinesterase activity without adverse cognitive-behavioral effects. Pharmacol Biochem Behav. 2010;94(3):477-481.
Sun QQ, Xu SS, Pan JL, et al. Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Zhongguo Yao Li Xue Bao. 1999;20(7):601-603.
Wang BS, Wang H, Wei ZH, et al. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer’s disease: an updated meta-analysis. J Neural Transm. 2009;116(4):457-465.
Koistinaho M, Koistinaho J. Interactions between Alzheimer’s disease and cerebral ischemia–focus on inflammation. Brain Res Brain Res Rev. 2005;48(2):240-250.