Apha GPC

(34) Alpha-GPC appears to be somewhat effective treating Alzheimer’s disease and works well in conjunction with standard therapies for this disease.
(35) A pilot study was done to test the effect of Alpha-GPC on physical strength. A 14% increase in power output was observed as assessed by bench throws. The study requires replication but the effect appears to be stronger than caffeine based on this study.
(36) One study using Alpha-GPC alongside both caffeine and phosphatidylserine has found increased attention and reaction time in persons undergoing acute stress.

References:
(34) https://examine.com/supplements/alpha-gpc/
(35) https://examine.com/supplements/alpha-gpc/#hem-power-output
(36) Hoffman JR, et al. The effects of acute and prolonged CRAM supplementation on reaction time and subjective measures of focus and alertness in healthy college students. J Int Soc Sports Nutr. (2010)

Ashwagandha

(42) Ashwagandha appears to significantly reduce the symptoms of stress and its symptoms (fatigue, temporary cognitive impairment, etc.) as well as biomarkers such as cortisol.
(43) Multiple studies have noted an improvement on cognitive tests for people with cognitive impairment, anxiety, and bipolar disorder.
(44) Ashwagandha is able to induce neurogenesis (the growth and development of nervous tissue), which is thought to play a rehabilitative role in cognitive decline

References:
(42) to (44) https://examine.com/supplements/ashwagandha/#neurology_neuroprotection

Bacopa Monnieri

(32) Studies demonstrate that Bacopa has positive benefits on multiple measures of cognitive performance. Bacopa recipients improved in delayed recall memory and reaction times.
(33) Bacopa has a significant anxiolytic (anti-anxiety) effect. It appears to modulate brain levels of the neurotransmitter serotonin. This has an effect on mood regulation, spatial memory, memory accuracy and the ability to process visual information.

References:
(33) https://www.ncbi.nlm.nih.gov/pubmed/18683852
(32) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153866/

CDP Choline

(37) Both of the molecules that this compound provide are neuroprotective and can potentially enhance learning.
(38) CDP Choline appears to promote cognition in otherwise healthy older adults.
(39) One study in older individuals given CDP-choline daily for 6 weeks has noted an increase in phosphocreatine (7%) and ATP (14%). Lower doses were ineffective.
(40) Piracetam and CDP-Choline appear to be synergistic towards memory formation in otherwise healthy rodents.
Note: We are still wondering how to test rat memories?

References:
(37) & (38) & (40) & (41) https://examine.com/supplements/cdp-choline/

CoEnzyme Q10

(8) CoEnzyme Q10 protects against free radical damage in the brain (9) and it is fundamental in powering the body’s production of energy through the ATP cycle.

References:
(8) PETILLO, D. and HULTIN, H. O. (2008), “UBIQUINONE-10 AS AN ANTIOXIDANT”. Journal of Food Biochemistry, 32: 173–181. doi: 10.1111/j.1745-4514.2008.00151
(9) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178961/

Coffee Bean Extract

(66) Green coffee beans are the same as regular coffee beans, except that they haven’t been roasted yet. They are high in a substance called Chlorogenic Acid, used in the formation of cells.
(65) Research has indicated that the consumption of caffeinated coffee can potentially reduce long-term weight gain, Probably due to the thermogenic effects of caffeine as well as effects of GCE and other pharmacologically active substances present in coffee

References:
(65) Greenberg JA, Boozer CN, Geliebter A. Coffee, diabetes, and weight control. American Journal of Clinical Nutrition. 2006;84(4):682–693
(66) https://examine.com/supplements/green-coffee-extract/#sources-and-summary_composition

Guarana

(52) Caffeine combined with guarana’s other active ingredients seem to enhance energy metabolism by: increasing fat oxidation, enhancing energy expenditure, & increasing exercise performance. The increase on energy metabolism also benefits the brain, which consumes about a fifth of the body’s energy.
The seeds of a guarana berry contain approximately 4 times the amount of caffeine as a coffee bean.
(53) Methylmercury (MeHg) is a well-known environmental pollutant associated with neurological and developmental deficits in animals and humans. However, epidemiological data showed that people living in the Amazon region, although exposed to MeHg, do not present these effects probably due to the protective effect of certain foods. In this study a correlation was invesigated between the comsumption of guarana, a highly caffeinated fruit and consumed on a daily basis by Amazon people, and the potential protective effect against MeHg toxicity.

References:
(52) https://www.ncbi.nlm.nih.gov/pubmed/21612429 & https://www.ncbi.nlm.nih.gov/pubmed/12569111
(53) https://www.ncbi.nlm.nih.gov/pubmed/30915696

L-theanine

(57) L-theanine elevates levels of GABA, as well as other neurotransmitters, that work in the brain to regulate emotions, mood, concentration, alertness, and sleep, as well as appetite, energy, and other cognitive skills. Increasing levels of calming brain chemicals promotes relaxation and can help with sleep.
(58) Alpha brain waves are associated with a state of “wakeful relaxation.” That’s the state of mind you experience when meditating, being creative, or letting your mind wander in daydreaming. Alpha waves are also present during REM sleep. L-theanine appears to trigger the release of alpha-waves, which enhances relaxation, focus, and creativity. One of the appealing aspects of L-theanine is that it works to relax without sedating.

References:
(57) https://www.psychologytoday.com/us/blog/sleep-newzzz/201708/what-you-need-know-about-l-theanine

Lions Mane Mushroom

(48) Supplementation with Lion’s Mane (Yamabushitake) appears to significantly reduce the rate of cognitive decline seen in older persons.
(49) The neurotrophic factors found in Lion’s Mane are important in promoting the growth and differentiation of neurons.

References:
(48) https://examine.com/supplements/yamabushitake/#hem-cognitive-decline
(49) https://www.ncbi.nlm.nih.gov/pubmed/24266378

Maritime Pine Bark Extract

(45) An improvement in attention and cognitive function has been noted in students during academic testing
(46) Pycnogenol (Pine Bark Extract) taken once daily in 61 children with confirmed ADHD for 4 weeks was associated with improvements in hyperactivity and attention when compared to both placebo and baseline. The effect was temporary and the benefit returned to baseline 1 month after stopping treatment.
(47) Pycnogenol’s (Pine Bark Extract)’s increases blood flow and improves blood glucose control.

References:
(45) to (47) https://examine.com/supplements/pycnogenol/#neurology_cognition

N-Acetylcysteine

(67) N-acetylcysteine (NAC) is used to treat paracetamol overdose. It is recognized by the World Health Organization (WHO) as a relevant medication required in a basic health system.

References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320789/

NAD+

(18) A decline in NAD+ homeostasis contributes to aging and all its associated declining processes.
(19) Increasing evidence shows that NAD+ and NADH play important roles in multiple biological processes in brains, such as neurotransmission, learning and memory.
(20) Anecdotal evidence shows that a boost in mental and physical energy levels, a better mood, improved cognition and alertness are typical of this ingredient.

References:
(18) Chini CCS , Tarragó MG , Chini EN . NAD and the aging process: Role in life, death and everything in between [published online ahead of print November 5, 2016]. Mol Cell Endocrinol
(19) https://www.ncbi.nlm.nih.gov/pubmed/17127427
(20) https://nootropicsexpert.com/nadh/#how-does-nadh-feel

Panax Ginseng

(55) Supplementing with ginseng should boost your energy levels, both physical and mental energy. Ginseng has stimulant-like qualities and should help if you’re dealing with chronic fatigue. But unlike standard stimulants, your boost in energy will come with a more ‘relaxed’ feel.
(56) An increase in cognition is seen acutely in studies. It is thought to be due to anti-fatigue effects, with non-fatigued individuals not experiencing an increase in cognitive performance.

References:
(55) Li X.T., Chen R., Jin L.M., Chen H.Y. “Regulation on energy metabolism and protection on mitochondria of Panax ginseng polysaccharide.” American Journal of Chinese Medicine. 2009;37(6):1139-52.
(56) https://examine.com/supplements/panax-ginseng/

Piperine

Piperine is found in black pepper and is used for treating and preventing the aging process and its related mental conditions such as Alzheimer, Parkinson, senile dementia etc.) and loss of memory (23)
Recently, an interesting study shows that piperine was also effective in mood and cognitive disorder (24)
Piperine has good potential as an antioxidant and is therefore used in nutritional and therapeutical supplements (25)

References:
(23) https://openchemistryjournal.com/VOLUME/3/PAGE/75/FULLTEXT/
(24) Wattanathorn J, Chonpathompikunlert P, Muchimapura S, Priprem A, Tankamnerdthai O. Piperine, the potential functional food for mood and cognitive disorders. Food Chem Toxicol 2008; 46(9): 3106-10.
(25) https://openchemistryjournal.com/VOLUME/3/PAGE/75/FULLTEXT/

PQQ

(21) PQQ & CoEnzyme Q10 are great partners for improved memory recall.
(22) Studies on PQQ supplements have shown evidence of improved mitochondria-related functions which translate to greater energy use.

References:
(21) https://www.tandfonline.com/doi/full/10.1080/09168451.2015.1062715
(22) https://www.ncbi.nlm.nih.gov/pubmed/24231099

Rhodiola Rosea

(59) Rhodiola Rosea is known as an adaptogen and therefore helps your body adapt to stress, both mental and physical.
(67) In one study, it was shown that by reducing these symptoms during a test on night shift ER doctors, a performance improvement of 20% on work tasks was found.
(67)
(60) Rhodiola can reduce general fatigue under stressful conditions.
(61) Memory improvements have been noted in persons with cognitive impairment when given a combination of Rhodiola, Magnesium and B-vitamins.

References:
(59) https://examine.com/supplements/rhodiola-rosea/
(67) https://www.ncbi.nlm.nih.gov/pubmed/11081987
(60) https://www.ncbi.nlm.nih.gov/pubmed/11081987
(61) Fintelmann V, Gruenwald J. Efficacy and tolerability of a Rhodiola rosea extract in adults with physical and cognitive deficiencies. Adv Ther. (2007)

Selenium

Low selenium levels are linked to poor cognition and memory due to low neurotransmitter levels in the brain. (6)
Human studies confirm that Selenium helps prevent and treat brain disorders (7)

References:
(6) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147716/
(7) Sanmartin C., Plano D., Font M., Palop J. A. (2011). Selenium and clinical trials: new therapeutic evidence for multiple diseases. Curr. Med. Chem. 18, 4635–4650 10.2174/092986711797379249

Shilajit

(62) Recent investigations have been made into the use of Shilajit to treat cognitive disorders associated with aging, and cognitive stimulation.
(63) A research study noted that shilajit could fight off and kill many different viruses in isolated environments, including some herpes viruses.
(64) Researchers noted that shilajit might help improve cell functions in the body, which means it may reduce fatigue at the source of the problem and increase energy levels naturally.

References:
(62) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296184/
(63) In vitro evaluation of the antiviral properties of Shilajit and investigation of its mechanisms of action / Cagno, Valeria*;
Donalisio, Manuela*; Civra, Andrea; Cagliero, Cecilia; Rubiolo, Patrizia; Lembo, David. – In: JOURNAL OF ETHNOPHARMACOLOGY. – ISSN 0378-8741. – 166(2015), pp. 129-34-134.
(64) https://www.sciencedirect.com/science/article/pii/S0378874112003893?

Vitamin B12 (cobalamin)

(12) Low Vitamin B12 is a factor in the development of Alzeimer’s Disease. It is suggested as a monitoring serum in the elderly for prevention of the disease.
(13) Vitamin B12 is being successfully tested as a treatment for patients with brain damage from methamphetamine addiction which demonstrates it’s ability to help the brain form healthy brain cells.

References:
(12) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960763/
(13) Wang H.X. et. Al “Vitamin B12 and folate in relation to the development of Alzheimer’s disease” Neurology May 8, 2001 vol. 56 no. 9 1188-1194

Vitamin B3 (Niacin)

(27) Vitamin B3 (Niacin) is a precursor to NAD and NADH, which plays a role in healthy neurotransmitter function and synthesis, including for dopamine, norepinephrine, and serotonin.
(28) Niacin appears to play a role in protecting neurons from traumatic injury and has been implicated in 3 key neurodegenerative conditions: Alzheimer’s, Parkinson’s, and Huntington’s diseases.
(29) Niacin influences a wide range of cellular activities that provide energy generation, cellular protection and repair, and this is seen in numerous body systems as well as the Central Nervous System.

References:
(27) https://www.ncbi.nlm.nih.gov/pubmed/9805207
(28) & (29) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966847/

Vitamin B9 (Folate)

Folic acid (Vitamin B9) gets its name from where it is found naturally: in leafy greens (folium = leaf). Folic acid is important for functioning of the nervous system at all ages, especially in the womb. (14)
Fautly folate metabolism causes a pattern of cognitive dysfunction that resembles ageing (15)

References:
(14) & (15) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123448/

Vitamin B6 (Pyridoxine)

(29) Vitamin B6 is a limiting factor in the synthesis of neurotransmitters such as dopamine & serotonin and therefore needs to be present in for them to be produced. Even a mild deficiency results in down-regulation of GABA and serotonin synthesis.
(30) The role of Vitamin B6 as an anti-inflammatory contributes to numerous pathological states including dementia and cognitive decline.

References:
(29) & (30) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/

Vitamin B5 (Pantothenic Acid)

Since Pantothetic Acid is the substrate which eventually produces CoA, it serves in the brain by assisting the synthesis of various neurotransmitters.

References:
https://examine.com/supplements/vitamin-b5/#neurology_neuropharmacology

Vitamin C (Ascorbic Acid)

(50) Vitamin C plays a role in the differentiation and maturation of neurons. It helps form the protective myelin sheath around neurons. It also speeds up impulse transmission, making the vitamin crucial to cognitive performance.
(51) The antioxidant effects of vitamin C have been demonstrated in many experiments and is praised as one of the highlights of taking this vitamin supplement.

References:
(50) https://www.psychologytoday.com/intl/articles/201801/the-cognitive-benefits-vitamin-c
(51) https://www.ncbi.nlm.nih.gov/pubmed/12569111

Vitamin D

(11) Active vitamin D influences brain and neuron development (10). It’s antioxidant effect protects the brain.

References:
(10) Garcion, E., Wion-Barbot, N., Montero-Menei, C. N., Berger, F. & Wion, D. New clues about vitamin D functions in the nervous system. Trends in Endocrinology & Metabolism 13, 100–105 (2002).
(11) Brown, J., Bianco, J. I., McGrath, J. J. & Eyles, D. W. 1, 25-Dihydroxyvitamin D(3) induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neuroscience Letters

Zinc

(26) Changes in brain zinc levels have been implicated in many neurological disorders including impaired brain development, neurodegenerative disorders such as Alzheimer’s disease, and mood disorders.

References:
(26) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757551/