Ingredients

Chill

Cat's Claw
(250 mg)

Nootropic Description

A powerful antioxidant and mood regulator, Cat’s Claw is a wood vine found in the tropics of Central and South America. Cat’s Claw not only decreases inflammation, but it also indirectly increases serotonin by boosting tryptophan levels, encouraging relaxation and pain relief. Those that supplement with Cat’s Claw usually report a subtle relaxing and anti-anxiety effect.

Supporting Studies

1. Aqueous extracts of Cat’s Claw may be beneficial for DNA repair, immune function, and Parkinson’s Disease

2. The DNA repair witnessed in vivo in the rat model was confirmed in a human study

3. Cat’s Claw extract boosted tryptophan and vitamin B3 levels which may enhance mood

4. Cat’s Claw possesses antioxidant and anti-inflammatory properties independent of the presence of oxindole or pentacyclic alkaloids

5. Cat’s Claw can mitigate pain through serotonin (5-HT2) receptors

Supporting Studies Citations

  1. 1. Shi, Z., Lu, Z., Zhao, Y., Wang, Y., Zhao-Wilson, X., Guan, P., ... & Zhao, B. (2013). Neuroprotective effects of aqueous extracts of Uncaria tomentosa: Insights from 6-OHDA induced cell damage and transgenic Caenorhabditis elegans model. Neurochemistry international, 62(7), 940-947.
  2. 2. Sheng, Y., Bryngelsson, C., & Pero, R. W. (2000). Enhanced DNA repair, immune function and reduced toxicity of C-MED-100™, a novel aqueous extract from Uncaria tomentosa. Journal of Ethnopharmacology, 69(2), 115-126.
  3. 3. Sheng, Y., Li, L., Holmgren, K., & Pero, R. W. (2001). DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study. Phytomedicine, 8(4), 275-282.
  4. 4. Pero, R. W., & Lund, H. (2011). Dietary quinic acid supplied as the nutritional supplement AIO+ AC‐11® leads to induction of micromolar levels of nicotinamide and tryptophan in the urine. Phytotherapy Research, 25(6), 851-857.
  5. 5. Jürgensen, S., DalBó, S., Angers, P., Santos, A. R. S., & Ribeiro-do-Valle, R. M. (2005). Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa. Pharmacology Biochemistry and Behavior, 81(3), 466-477.
  6. 6. Sandoval, M., Okuhama, N. N., Zhang, X. J., Condezo, L. A., Lao, J., Angeles, F. M., ... & Miller, M. J. S. (2002). Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine, 9(4), 325-337.

Valerian Root
(200 mg; Standardized to .8% Valerenic Acid)

Nootropic Description

Valerian root is used for sleep disorders, anxiety, and psychological stress. Valerian works by relaxing blood vessels, modulating serotonin and norepinephrine, and inhibiting the breakdown of GABA in the brain. Those that supplement with valerian report a relaxing effect that facilitates sleep.

Supporting Studies

1. Extracts of valerian root improve sleep quality without the “hangover effect” other sleep agents cause

2. Valerenic acid decreases stress levels by modulating serotonin and norepinephrine in the hippocampus and amygdala

3. Valerian improves blood flow by acting as a smooth muscle dilator in the feline pulmonary vascular bed

4. Seda-Kneipp, a compound preparation of valerian and hops reduced noise induced disturbance of sleep by increasing slow-wave and REM sleep

5. Valerian inhibits the breakdown and of GABA in the brain, reducing anxiety, increasing sedation, and enhancing relaxation

6. Valerian helps reduce symptoms of restlessness, dyssomnia, and OCD

Supporting Studies Citations

  1. 1. Bent, S., Padula, A., Moore, D., Patterson, M., & Mehling, W. (2006). Valerian for sleep: a systematic review and meta-analysis. The American journal of medicine, 119(12), 1005-1012.
  2. 2. Jung, H. Y., Yoo, D. Y., Nam, S. M., Kim, J. W., Choi, J. H., Yoo, M., ... & Hwang, I. K. (2015). Valerenic Acid Protects Against Physical and Psychological Stress by Reducing the Turnover of Serotonin and Norepinephrine in Mouse Hippocampus-Amygdala Region. Journal of medicinal food, 18(12), 1333-1339.
  3. 3. Fields, A. M., Richards, T. A., Felton, J. A., Felton, S. K., Bayer, E. Z., Ibrahim, I. N., & Kaye, A. D. (2003). Analysis of responses to valerian root extract in the feline pulmonary vascular bed. The Journal of Alternative & Complementary Medicine, 9(6), 909-918.
  4. 4. Müller-Limmroth, W., & Ehrenstein, W. (1977). Experimental studies of the effects of Seda-Kneipp on the sleep of sleep disturbed subjects; implications for the treatment of different sleep disturbances (author's transl). Medizinische Klinik, 72(25), 1119-1125.
  5. 5. Houghton, P. J. (1999). The scientific basis for the reputed activity of Valerian. Journal of Pharmacy and Pharmacology, 51(5), 505-512.
  6. 6. Nemeroff, C. B. (2003). The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacology bulletin, 37(4), 133-146.
  7. 7. Müller, S. F., & Klement, S. (2006). A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine, 13(6), 383-387.
  8. 8. Pakseresht, S., Boostani, H., & Sayyah, M. (2011). Extract of valerian root (Valeriana officinalis L.) vs. placebo in treatment of obsessive-compulsive disorder: a randomized double-blind study. Journal of Complementary and Integrative Medicine, 8(1).

Lemon Balm Extract
(150 mg; Standardized to 5% Rosmarinic Acid)

Nootropic Description

Lemon balm, formally known as Melissa officinalis, is a part of the mint family that has been used since the Middle Ages. Lemon balm is a natural remedy to improve sleep, reduce anxiety, and promote longevity.

Supporting Studies

1. Lemon balm infusion in radiology unit workers resulted in a significant improvement in plasma levels of catalase, superoxide dismutase, and glutathione peroxidase and a marked reduction in plasma DNA damage, myeloperoxidase, and lipid peroxidation.

2. Lemon balm, or Melissa officinalis, can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer’s disease.

3. Lemon Balm may increase cell proliferation, neuroblast differentiation, and integration into granule cells by decreasing serum corticosterone levels and increasing GABA levels in the mouse

4. 600mg doses of lemon balm ameliorated the negative mood effects of the Defined Intensity Stressor Simulation increasing feeling of calmness and reducing feelings of alertness

5. Lemon balm supplementation may improve memory formation and retention in healthy individuals

Supporting Studies Citations

  1. 1. Zeraatpishe, A., Oryan, S., Bagheri, M. H., Pilevarian, A. A., Malekirad, A. A., Baeeri, M., & Abdollahi, M. (2011). Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation. Toxicology and industrial health, 27(3), 205-212.
  2. 2. Kennedy, D. O., Wake, G., Savelev, S., Tildesley, N. T. J., Perry, E. K., Wesnes, K. A., & Scholey, A. B. (2003). Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology, 28(10), 1871.
  3. 3. Yoo, D. Y., Choi, J. H., Kim, W., Yoo, K. Y., Lee, C. H., Yoon, Y. S., ... & Hwang, I. K. (2011). Effects of Melissa officinalis L.(lemon balm) extract on neurogenesis associated with serum corticosterone and GABA in the mouse dentate gyrus. Neurochemical research, 36(2), 250-257..
  4. 4. Kennedy, D. O., Little, W., & Scholey, A. B. (2004). Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosomatic medicine, 66(4), 607-613.
  5. 5. Kennedy, D. O., Scholey, A. B., Tildesley, N. T. J., Perry, E. K., & Wesnes, K. A. (2002). Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacology Biochemistry and Behavior, 72(4), 953-964.
  6. 6. Examine.com. (2018, June 14). Melissa officinalis Supplement - Science-based Review on Benefits, Dosage, Side Effects. Retrieved from https://examine.com/supplements/melissa-officinalis/
  7. 7. Müller, S. F., & Klement, S. (2006). A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine, 13(6), 383-387.

Ashwagandha Root
(150 mg; Sensoril)

Nootropic Description

An ancient herb native to India, Ashwagandha has been used to relieve stress, increase concentration, and improve energy levels for centuries. Ashwagandha lowers cortisol concentration in the brain, lowering stress, while encouraging cellular antioxidation. Users typically report reductions in stress and anxiety.

Supporting Studies

1. Ashwagandha substantially reduced serum cortisol levels, significantly reducing stress relative to the placebo

2. Ashwagandha decreases the effects of fatigue and increases testosterone levels in aging men

3. Ashwagandha extract can improve cognitive and psychomotor performance and may, therefore, be a valuable adjunct in the treatment of diseases associated with cognitive impairment

4. Ashwagandha has been shown to improve physical reaction time, promoting mental acuity

5. Ashwagandha may be effective in enhancing both immediate and general memory, executive function, attention, and information processing speed in people with mild cognitive impairment

Supporting Studies Citations

  1. 1. Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian journal of psychological medicine, 34(3), 255.
  2. 2. Lopresti, A. L., Drummond, P. D., & Smith, S. J. (2019). A randomized, double-blind, placebo-controlled, crossover study examining the hormonal and vitality effects of ashwagandha (Withania somnifera) in aging, overweight males. American journal of men's health, 13(2), 1557988319835985.
  3. 3. Pingali, U., Pilli, R., & Fatima, N. (2014). Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants. Pharmacognosy research, 6(1), 12.
  4. 4. Ashwagandha Shown to Improve Reaction Time in Men. (n.d.). Retrieved from https://www.naturalhealthresearch.org/ashwagandha-shown-improve-reaction-time-men/
  5. 5. Choudhary, D., Bhattacharyya, S., & Bose, S. (2017). Efficacy and safety of Ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions. Journal of dietary supplements, 14(6), 599-612.

Magnesium
(60 mg; as Magnesium Glycinate)

Nootropic Description

Magnesium is an essential mineral in the brain that regulates glutamate receptors partially responsible for short-term and long-term memory formation. Magnesium reduces the release of adrenocorticotropic hormone, regulating cortisol in the brain. These mechanisms therefore allow magnesium to simultaneously increase energy levels while decreasing general anxiety.

Supporting Studies

1. There is an inverse association between standardized energy-adjusted magnesium intake and standardized depression scores after accounting for age, gender, blood pressure, socioeconomic, and lifestyle variables

2. Elevated brain magnesium levels via dietary supplementation can boost NR2B expression enhancing synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents

3. Magnesium decreases levels of B-amyloid protein, a plaque between neurons implicated in Alzheimer’s Disease, mitigating memory deficits

4. Chronically elevating plasma magnesium improves hippocampal frequency potentiation and reversal learning in aged and young rats

5. Magnesium deficiency is not uncommon in the United States and may perturb bone and mineral metabolism and be a risk factor for osteoporosis

6. Children diagnosed with ADD or ADHD had significantly higher rates of magnesium deficiency

Supporting Studies Citations

  1. 1. Jacka, F. N., Overland, S., Stewart, R., Tell, G. S., Bjelland, I., & Mykletun, A. (2009). Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study. Australian and New Zealand Journal of Psychiatry, 43(1), 45-52.
  2. 2. Wang, D., Jacobs, S. A., & Tsien, J. Z. (2014). Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline. Expert opinion on therapeutic targets, 18(10), 1121-1130.
  3. 3. Yu, X., Guan, P. P., Guo, J. W., Wang, Y., Cao, L. L., Xu, G. B., ... & Wang, P. (2015). By suppressing the expression of anterior pharynx-defective-1α and-1β and inhibiting the aggregation of β-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice. The FASEB Journal, 29(12), 5044-5058.
  4. 4. Landfield, P. W., & Morgan, G. A. (1984). Chronically elevating plasma Mg2+ improves hippocampal frequency potentiation and reversal learning in aged and young rats. Brain research, 322(1), 167-171.
  5. 5. Rude, R. K., Singer, F. R., & Gruber, H. E. (2009). Skeletal and hormonal effects of magnesium deficiency. Journal of the American College of Nutrition, 28(2), 131-141.
  6. 6. Kozielec, T., & Starobrat-Hermelin, B. (1997). Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). Magnesium Research, 10(2), 143-148.

Zinc
(12 mg; as Zinc Orotate)

Nootropic Description

Zinc is an essential mineral that is necessary for the catalytic activity of over 100 enzymes. Zinc is primarily used to buttress immune responses by acting as a strong antioxidant, but it has also been shown to reduce hyperactive and impulsive symptoms in individuals with attention deficits.

Supporting Studies

1. Zinc treated cells release almost 100% of catecholamines slowing down exocytotic release.

2. Zinc deficiency played a causal role in the induction of depressive symptoms, the reduction of neurogenesis and neuronal survival, the impairment of learning and memory ability

3. The normalization of zinc intake in stroke patients with low mineral intake may enhance neurological recovery

4. Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms

5. Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term potentiation of mossy fiber-CA3 synapses making zinc critical to proper function of hippocampal circuitry

Supporting Studies Citations

  1. 1. Ren, L., Pour, M. D., Majdi, S., Li, X., Malmberg, P., & Ewing, A. G. (2017). Zinc Regulates Chemical‐Transmitter Storage in Nanometer Vesicles and Exocytosis Dynamics as Measured by Amperometry. Angewandte Chemie International Edition, 56(18), 4970-4975.
  2. 2. Szewczyk, B., Kubera, M., & Nowak, G. (2011). The role of zinc in neurodegenerative inflammatory pathways in depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(3), 693-701.
  3. 3. Aquilani, R., Baiardi, P., Scocchi, M., Iadarola, P., Verri, M., Sessarego, P., ... & Viglio, S. (2009). Normalization of zinc intake enhances neurological retrieval of patients suffering from ischemic strokes. Nutritional neuroscience, 12(5), 219-225.
  4. 4. Bilici, M., Yıldırım, F., Kandil, S., Bekaroğlu, M., Yıldırmış, S., Değer, O., ... & Aksu, H. (2004). Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 28(1), 181-190.
  5. 5. Pan, E., Zhang, X. A., Huang, Z., Krezel, A., Zhao, M., Tinberg, C. E., ... & McNamara, J. O. (2011). Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term potentiation of mossy fiber-CA3 synapse. Neuron, 71(6), 1116-1126.

Lithium
(2 mg; as Lithium Orotate

Nootropic Description

Lithium orotate acts as a neuroprotectant by preventing glutamate toxicity, increasing the expression of bcl-2, and increasing the proliferation of brain derived neurotrophic factor. Lithium orotate also may inhibit plaques from forming between neurons, enhancing synaptic communication. Users that supplement with lithium orotate report calming effects and a reduction in anxiety.

Supporting Studies

1. Chronic lithium treatment has been demonstrated to increase bcl-2, a neuroprotectant responsible for increasing the regeneration of axons in the central nervous system

2. Lithium increases the levels of N-acetyl aspartate in the brain which is strongly associated with higher IQ scores.

3. Lithium prevents neuronal death by inhibiting the overactivity of glutamate, a potential cause for Alzheimer’s, Huntington’s, Parkinson’s, and other neurodegenerative diseases

4. Lithium exhibited robust beneficial effects in the treatment and prevention of Traumatic Brain Injury, alleviating cognitive and motor deficits.

5. Long-term use of lithium is associated with preservation of recollective memory function and increased hippocampal size in vivo.

6. Evidence indicates that lithium and imipramine can stabilize the physiological consequences of norepinephrine.

7. Lithium increased expression of brain derived neurotrophic factor and other genes associated with neuroprotection and decreased the expression of pro-apoptotic genes.

Supporting Studies Citations

  1. 1. Manji, H. K., Moore, G. J., & Chen, G. (1999). Lithium at 50: have the neuroprotective effects of this unique cation been overlooked?. Biological psychiatry, 46(7), 929-940.
  2. 2. Moore, G. J., Bebchuk, J. M., Hasanat, K., Chen, G., Seraji-Bozorgzad, N., Wilds, I. B., ... & Manji, H. K. (2000). Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects?. Biological psychiatry, 48(1), 1-8.
  3. 3. Aydin, K., Uysal, S., Yakut, A., Emiroglu, B., & Yılmaz, F. (2012). N-acetylaspartate concentration in corpus callosum is positively correlated with intelligence in adolescents. Neuroimage, 59(2), 1058-1064.
  4. 4. Hashimoto, R., Fujimaki, K., Jeong, M. R., Christ, L., & Chuang, D. M. (2003). Lithium‐induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: a role in neuroprotection against N‐methyl‐D‐aspartate receptor‐mediated excitotoxicity. FEBS letters, 538(1-3), 145-148.
  5. 5. Leeds, P. R., Yu, F., Wang, Z., Chiu, C. T., Zhang, Y., Leng, Y., ... & Chuang, D. M. (2014). A new avenue for lithium: intervention in traumatic brain injury. ACS chemical neuroscience, 5(6), 422-433.
  6. 6. Yucel, K., McKinnon, M. C., Taylor, V. H., Macdonald, K., Alda, M., Young, L. T., & MacQueen, G. M. (2007). Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Psychopharmacology, 195(3), 357-367.
  7. 7. Leeds, P. R., Yu, F., Wang, Z., Chiu, C. T., Zhang, Y., Leng, Y., ... & Chuang, D. M. (2014). A new avenue for lithium: intervention in traumatic brain injury. ACS chemical neuroscience, 5(6), 422-433.
  8. 8. Dwivedi, T., & Zhang, H. (2015). Lithium-induced neuroprotection is associated with epigenetic modification of specific BDNF gene promoter and altered expression of apoptotic-regulatory proteins. Frontiers in neuroscience, 8, 457.

Glycine
(as Magnesium Glycinate)

Nootropic Description

Glycine is an amino acid that is used to create proteins necessary for cell growth and tissue maintenance. It is a building block of glutathione, one of the bodies most effective antioxidants, and it helps to synthesize creatine, a substance that promotes muscular energy levels.

Supporting Studies

1. Glycine use has led to reports of improved sleep quality

2. Glycine boost muscle recovery and possesses anti-aging effects by stimulating human growth hormone, stimulating cartilage and joint preservation, and decreasing inflammation

3. Research that shows the importance of glycine in the creation of the most proliferous antioxidant, glutathione

4. Glycine has been shown to have beneficial effects on brain function and neurodegenerative diseases through the biosynthesis of creatine

5. Glycine effectively promotes muscle growth through the biosynthesis of creatine

Supporting Studies Citations

  1. 1. Inagawa, K., Hiraoka, T., Kohda, T., Yamadera, W., & Takahashi, M. (2006). Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep and Biological Rhythms, 4(1), 75-77.
  2. 2. Yamadera, W., Inagawa, K., Chiba, S., Bannai, M., Takahashi, M., & Nakayama, K. (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms, 5(2), 126-131.
  3. 3. Ham, D. J., Murphy, K. T., Chee, A., Lynch, G. S., & Koopman, R. (2014). Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia. Clinical nutrition, 33(3), 448-458.
  4. 4. Bannai, M., Kawai, N., Ono, K., Nakahara, K., & Murakami, N. (2012). The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in neurology, 3, 61.
  5. 5. Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation–. The American journal of clinical nutrition, 94(3), 847-853.
  6. 6. Avgerinos, K. I., Spyrou, N., Bougioukas, K. I., & Kapogiannis, D. (2018). Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental gerontology, 108, 166-173.
  7. 7. Branch, J. D. (2003). Effect of creatine supplementation on body composition and performance: a meta-analysis. International journal of sport nutrition and exercise metabolism, 13(2), 198-226.
  8. 8. Chilibeck, P. D., Kaviani, M., Candow, D. G., & Zello, G. A. (2017). Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis. Open access journal of sports medicine, 8, 213.
  9. 9. Lanhers, C., Pereira, B., Naughton, G., Trousselard, M., Lesage, F. X., & Dutheil, F. (2017). Creatine supplementation and upper limb strength performance: A systematic review and meta-analysis. Sports medicine, 47(1), 163-173.

Inositol
(12 mg; as Inositol Hexanicotinate)

Nootropic Description

Inositol is a vital nutrient that is essential for building cell membranes, repairing DNA, and exporting nuclear RNA. Inositol also appears to counteract mild stress and anxiety, but has been used for more serious cognitive imbalances such as OCD, PTSD, panic attacks, and clinical depression. Users who supplement with inositol report better sleep and reductions in anxiety.

Supporting Studies

1. The inositol derivative, myo-inositol, may enhance DNA repair, nuclear RNA export, and synaptic membrane trafficking.

2. Inositol led to decreased levels of LDL-cholesterol (bad cholesterol) and increased levels of HDL-cholesterol (good cholesterol) when treating hirsutism

3. Chronic high dosage supplementation of inositol is associated with reductions in panic attack frequency.

4. Decreases in anxiety symptoms are associated with chronic high dosage of inositol

Supporting Studies Citations

  1. 1. Fisher, S. K., Novak, J. E., & Agranoff, B. W. (2002). Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance. Journal of neurochemistry, 82(4), 736-754.
  2. 2. Minozzi, M., D'Andrea, G., & Unfer, V. (2008). Treatment of hirsutism with myo-inositol: a prospective clinical study. Reproductive biomedicine online, 17(4), 579-582.
  3. 3. Palatnik, A., Frolov, K., Fux, M., & Benjamin, J. (2001). Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. Journal of clinical psychopharmacology, 21(3), 335-339.
  4. 4. Benjamin, J., Levine, J., Fux, M., Aviv, A., Levy, D., & Belmaker, R. H. (1995). Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. American Journal of Psychiatry, 152(7), 1084-1086.
  5. 5. Palatnik, A., Frolov, K., Fux, M., & Benjamin, J. (2001). Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. Journal of clinical psychopharmacology, 21(3), 335-339.
  6. 6. Benjamin, J., Levine, J., Fux, M., Aviv, A., Levy, D., & Belmaker, R. H. (1995). Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. American Journal of Psychiatry, 152(7), 1084-1086.
  7. 7. Gelber, D., Levine, J., & Belmaker, R. H. (2001). Effect of inositol on bulimia nervosa and binge eating. International Journal of Eating Disorders, 29(3), 345-348.
  8. 8. Fux, M., Levine, J., Aviv, A., & Belmaker, R. H. (1996). Inositol treatment of obsessive-compulsive disorder. American Journal of Psychiatry, 153(9), 1219-1221.

Cannabidiol
(5mg; as 99% CBD Isolate from Hemp)

Nootropic Description

Beneficial effects of CBD have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. In addition to CBD's many mood regulating benefits, it has also been shown to improve the brain’s health and functional efficiency by reducing neuronal loss, increasing brain derived neurotrophic factor, and enhancing dendritic development.

Supporting Studies

1. Chronic treatment with cannabidiol at a dose of 15 mg/kg and imipramine at a dose of 30mg/kg increased BDNF levels in rat amygdalas.

2. CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress, and modulates cell fate regulatory pathways like autophagy critical for neuronal survival in neurodegenerative experimental models.

3. CBD administration after middle cerebral artery occlusion led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation.

4. Treatment with a high dose of CBD 100mg/kg or a low dose of 10mg/kg elicited significant antidepressant-like behavioral effects in forced swim test, following increased mRNA expression of brain-derived neurotrophic factor and synaptophysin in the prefrontal cortex and hippocampus.

5. CBD may be used as a pharmacological tool to improve neurological dysfunctions caused by trauma by positively modifying the behavioral phenotype associated with traumatic brain injuries

6. By increasing brain derived neurotrophic factor signaling and synaptogenesis in the prefrontal cortex, cannabidiol induces rapid and sustained antidepressant-like effects

7. Cannabidiol treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus and prefrontal cortex, demonstrating CBD’s neuroprotective properties

8. Short-term cannabidiol treatment in mice with bilateral common carotid artery occlusion increased hippocampal brain derived neurotrophic factor, neurogenesis, and dendritic restructuring while attenuating hippocampal neurodegeneration and reducing gliosis

Supporting Studies Citations

  1. 1. Réus, G. Z., Stringari, R. B., Ribeiro, K. F., Luft, T., Abelaira, H. M., Fries, G. R., ... & Crippa, J. A. (2011). Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala. Acta neuropsychiatrica, 23(5), 241-248.
  2. 2. Campos, A. C., Fogaça, M. V., Scarante, F. F., Joca, S. R., Sales, A. J., Gomes, F. V., ... & Guimarães, F. S. (2017). Plastic and neuroprotective mechanisms involved in the therapeutic effects of cannabidiol in psychiatric disorders. Frontiers in pharmacology, 8, 269.
  3. 3. Ceprián, M., Jiménez-Sánchez, L., Vargas, C., Barata, L., Hind, W., & Martínez-Orgado, J. (2017). Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke. Neuropharmacology, 116, 151-159.
  4. 4. Xu, C., Chang, T., Du, Y., Yu, C., Tan, X., & Li, X. (2019). Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model. Environmental toxicology and pharmacology, 103202.
  5. 5. Belardo, C., Iannotta, M., Boccella, S., Rubino, R. C., Ricciardi, F., Infantino, R., . . . Guida, F. (2019). Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury. Frontiers in Pharmacology, 10. doi:10.3389/fphar.2019.00352
  6. 6. Sales, A. J., Fogaça, M. V., Sartim, A. G., Pereira, V. S., Wegener, G., Guimarães, F. S., & Joca, S. R. (2019). Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Molecular neurobiology, 56(2), 1070-1081.
  7. 7. Campos, A. C. D., Brant, F., Miranda, A. S., Machado, F. S., & Teixeira, A. L. (2015). Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria. Neuroscience, 289, 166-180.
  8. 8. Mori, M. A., Meyer, E., Soares, L. M., Milani, H., Guimarães, F. S., & de Oliveira, R. M. W. (2017). Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 75, 94-105.

Vitamin B3
(50 mg; as Inositol Hexanicotinate)

Nootropic Description

Vitamin B3 is a precursor to the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) which are necessary for cellular communication, metabolism, and DNA repair. Supplementation of Vitamin B3 also has a strong association with increasing HDL levels while decreasing LDL levels, possibly decreasing the possibility of atherosclerosis, heart disease, and other cardiac dysfunctions.

Supporting Studies

1. NAD+ and NADH, coenzymes synthesized with vitamin B3, mediate energy metabolism, mitochondrial functions, calcium homeostasis, and cell health.

2. Vitamin B3 is believed to cause improvements in energy production due to its role as a precursor of NAD, indirectly increasing the amount of energy available in a cell

3. A combination of coenzyme Q10 and nicotinamide protected against mild and moderate depletion of dopamine.

4. Vitamin B3 promotes synaptic plasticity and axon growth in stroke patients, partially mediated by brain-derived neurotrophic factor and tropomyosin-related kinase B pathways.

5. Short-term niacin treatment might improve endothelial function in patients with low HDL-C levels.

6.20 nondiabetic, dyslipidemic men with metabolic syndrome receiving slow release niacin for 8 weeks saw a significant reduction in triglycerides and vLDL and an increase in HDL cholesterol.

7. Vitamin B3 exerts anti inflammatory effects on macrophages that assist in reducing risk of atherosclerosis.

8. Short-term cannabidiol treatment in mice with bilateral common carotid artery occlusion increased hippocampal brain derived neurotrophic factor, neurogenesis, and dendritic restructuring while attenuating hippocampal neurodegeneration and reducing gliosis

Supporting Studies Citations

  1. 1. Ying, W. (2007). NAD and NADH in Neuronal Death. Journal of Neuroimmune Pharmacology, 2(3), 270-275. doi:10.1007/s11481-007-9063-5
  2. 2. Stephanie Liou (2010). Nicotinamide. Retrieved from https://hopes.stanford.edu/nicotinamide/
  3. 3. Schulz, J. B., Henshaw, D. R., Matthews, R. T., & Beal, M. F. (1995). Coenzyme Q10 and nicotinamide and a free radical spin trap protect against MPTP neurotoxicity. Experimental neurology, 132(2), 279-283.
  4. 4. Cui, X., Chopp, M., Zacharek, A., Roberts, C., Buller, B., Ion, M., & Chen, J. (2010). Niacin treatment of stroke increases synaptic plasticity and axon growth in rats. Stroke, 41(9), 2044-2049.
  5. 5. Figueiredo, V. N., Vendrame, F., Colontoni, B. A., Quinaglia, T., Matos-Souza, J. R., Moura, F. A., ... & Sposito, A. C. (2014). Short-term effects of extended-release niacin with and without the addition of laropiprant on endothelial function in individuals with low HDL-C: a randomized, controlled crossover trial. Clinical therapeutics, 36(6), 961-966.
  6. 6. Blond, E., Rieusset, J., Alligier, M., Lambert-Porcheron, S., Bendridi, N., Gabert, L., ... & Roth, H. (2014). Nicotinic acid effects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro study. Hormone and Metabolic Research, 46(06), 390-396.
  7. 7. Lipszyc, P. S., Cremaschi, G. A., Zubilete, M. Z., Bertolino, M. L. A., Capani, F., Genaro, A. M., & Wald, M. R. (2013). Niacin modulates pro-inflammatory cytokine secretion. A potential mechanism involved in its anti-atherosclerotic effect. The open cardiovascular medicine journal, 7, 90.
  8. 8. Zandi-Nejad, K., Takakura, A., Jurewicz, M., Chandraker, A. K., Offermanns, S., Mount, D., & Abdi, R. (2013). The role of HCA2 (GPR109A) in regulating macrophage function. The FASEB journal, 27(11), 4366-4374.

Vitamin B6
(10 mg; as Pyridoxine)

Nootropic Description

The active form of vitamin B6 is recognized as one of the most versatile organic cofactors in the body contributing to over 140 enzymatic activities. In particular, vitamin B6 acts as a cofactor for neurotransmitters like dopamine, epinephrine, GABA, norepinephrine, and serotonin. Through regulation homocysteine levels, B6 use is linked to decreased blood vessel inflammation leading to enhanced cerebral circulation. When supplementing with vitamin B6 to correct a deficiency, some users experience changes in mood such as reduced anxiety or depression and elevated energy levels

Supporting Studies

1. A study, conducted at Oxford University, with 156 elderly patients showed a 7-fold difference in gray matter shrinkage between the B6 treatment and control groups over a two-year period.

2. A 2008 review of research, over a 10-year period, covering 77 studies and 34,000 subjects showed a relationship between dementia and a deficit of B6.

3. Low vitamin B-6 status is correlated with cardiovascular disease, arthritis, inflammatory, and diabetes.

4. A Harvard study concludes that vitamin B6 may help prevent colorectal cancer in women.

5. Low concentrations of vitamin B6 coupled with elevated homocysteine levels associated with low B vitamin intake may increase the risk for Alzheimer’s and vascular dementia.

6. Vitamin B6 may decrease the risk of Parkinson disease through mechanisms likely unassociated with homocysteine metabolism.

7. Vitamin B6 in conjunction with sufficient folate supplementation may contribute to a reduction in the risk of breast cancer.

Supporting Studies Citations

  1. 1. Douaud, G., Refsum, H., de Jager, C. A., Jacoby, R., Nichols, T. E., Smith, S. M., & Smith, A. D. (2013). Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences, 110(23), 9523-9528.
  2. 2. Smith, A. D. (2008). The worldwide challenge of the dementias: a role for B vitamins and homocysteine?. Food and nutrition bulletin, 29(2_suppl1), S143-S172.
  3. 3. Sakakeeny, L., Roubenoff, R., Obin, M., Fontes, J. D., Benjamin, E. J., Bujanover, Y., ... & Selhub, J. (2012). Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of US adults. The Journal of nutrition, 142(7), 1280-1285.
  4. 4. Harvard Health Publishing. (n.d.). Vitamin B6 may help prevent colorectal cancer in women. Retrieved from https://www.health.harvard.edu/newsletter_article/Vitamin_B6_may_help_prevent_colorectal_cancer_in_women
  5. 5. Smith, A. D. (2008). The worldwide challenge of the dementias: a role for B vitamins and homocysteine?. Food and nutrition bulletin, 29(2_suppl1), S143-S172.
  6. 6. De Lau, L. M. L., Koudstaal, P. J., Witteman, J. C. M., Hofman, A., & Breteler, M. M. B. (2006). Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease. Neurology, 67(2), 315-318.
  7. 7. Zhang, S. M., Willett, W. C., Selhub, J., Hunter, D. J., Giovannucci, E. L., Holmes, M. D., ... & Hankinson, S. E. (2003). Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. Journal of the National Cancer Institute, 95(5), 373-380.

Flow

Acetyl-L-Carnitine
(500 mg)

Nootropic Description

Acetyl-L-Carnitine (ALCAR) is an amino acid that is essential for optimal brain health and metabolic function. Due to its enhanced bioavailability, ALCAR is able to pass through cell membranes and help the transport of fatty acids into the mitochondria, supporting energy production, and it can cross the blood brain barrier where it catalyzes the production of acetylcholine. The boost in acetylcholine subsequently increases memory, learning, focus, and concentration. ALCAR also increases cerebral blood flow and is considered a neuroprotectant for its antioxidant properties. Users who supplement with ALCAR report improvements in energy, motivation, and cognition.

Supporting Studies

1. ALCAR effects include modulation of brain energy and phospholipid metabolism, neurotrophic factors and neurohormones, and synaptic morphology and transmission of multiple neurotransmitters.

2. A meta-analysis of a double-blind placebo-controlled experiment showed a statistically significant improvement in cognitive function for the ALCAR group in patients suffering from mild Alzheimer’s disease.

3. ALCAR was able to stimulate neurite (axons and dendrites) outgrowth similar to that of nerve growth factor (NGF) suggesting a potential role in therapeutics strategies designed to counteract degenerative diseases of the central nervous system.

4. ALCAR has been known to reduce the effects of chronic fatigue, and it is also more effective than amantadine for treating fatigue associated with multiple sclerosis.

5. Memory loss in old rats due to brain mitochondrial decay and RNA/DNA oxidation was partially reversed by ALCAR.

6. ALCAR acts as a precursor to acetylcholine via the enzyme systems choline acetyltransferase and carnitine acetyltransferase.

7. Pretreatment with ALCAR exerts effective neuroprotection against the MDMA-induced neurotoxicity at the mitochondrial level, reducing carbonyl formation, decreasing mtDNA deletion, improving the expression of the respiratory chain components and preventing the decrease of 5-HT levels in several regions of the rat brain.

Supporting Studies Citations

  1. 1. Pettegrew, J. W., Levine, J., & McClure, R. J. (2000). Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Molecular psychiatry, 5(6), 616.
  2. 2. Montgomery, S. A., Thal, L. J., & Amrein, R. (2003). Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. International clinical psychopharmacology, 18(2), 61-71.
  3. 3. Taglialatela, G., Navarra, D., Olivi, A., Ramacci, M. T., Werrbach-Perez, K., Perez-Polo, J. R., & Angelucci, L. (1995). Neurite outgrowth in PC12 cells stimulated by acetyl-L-carnitine arginine amide. Neurochemical research, 20(1), 1-9.
  4. 4. Tomassini, V., Pozzilli, C., Onesti, E., Pasqualetti, P., Marinelli, F., Pisani, A., & Fieschi, C. (2004). Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. Journal of the neurological sciences, 218(1-2), 103-108.
  5. 5. Liu, J., Head, E., Gharib, A. M., Yuan, W., Ingersoll, R. T., Hagen, T. M., ... & Ames, B. N. (2002). Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-α-lipoic acid. Proceedings of the National Academy of Sciences, 99(4), 2356-2361.
  6. 6. White, H. L., & Scates, P. W. (1990). Acetyl-L-carnitine as a precursor of acetylcholine. Neurochemical research, 15(6), 597-601.
  7. 7. Alves, E., Binienda, Z., Carvalho, F., Alves, C. J., Fernandes, E., de Lourdes Bastos, M., ... & Summavielle, T. (2009). Acetyl-L-carnitine provides effective in vivo neuroprotection over 3, 4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain. Neuroscience, 158(2), 514-523.

Citicoline
(150 mg)

Nootropic Description

Citicoline is a uniquely effective choline donor in that it splits into choline, an essential precursor for the neurotransmitter acetylcholine, and cytidine, a molecule that strengthens synapses by repairing neuronal membranes. Citicoline is one of the most important nootropics for memory, cognition, and general brain health. Individuals that supplement with Citicoline report increases in cognition and focus.

Supporting Studies

1. Citicoline acts as a neuroprotectant and memory enhancer in age related brain diseases by modifying the molecular and neurochemical parameters related to brain energy production.

2. Citicoline’s neuroprotective mechanisms include preserving the mitochondrial membranes and myelin, restoring levels of phosphatidylcholine (necessary for acetylcholine), stimulating the synthesis of the powerful antioxidant glutathione, and attenuating the oxidative damage done to lipids.

3. Citicoline increases brain energy (ATP) by 14% and speeds up the formation of brain membranes by 26% in healthy adults.

4. Citicoline enhances the incorporation of blood glucose in the brain and its metabolism while slightly increasing cerebral blood flow and decreasing the accumulation of lactate

5. Citicoline inhibited ischemia-induced decrease in cortical and striatal ATP levels after oxygen-glucose deprivation while increasing glutamate uptake

6. Supplementation of citicoline encouraged synthesis of acetylcholine and stimulated dopamine release.

7. The administration of uridine and choline (what citicoline breaks down to) improved selective attention and spatial learning in spontaneously hypertensive rats.

Supporting Studies Citations

  1. 1. Villa, R. F., Ferrari, F., & Gorini, A. (2012). Effect of CDP-choline on age-dependent modifications of energy-and glutamate-linked enzyme activities in synaptic and non-synaptic mitochondria from rat cerebral cortex. Neurochemistry international, 61(8), 1424-1432.
  2. 2. Adibhatla, R. M., Hatcher, J. F., & Dempsey, R. J. (2002). Citicoline: neuroprotective mechanisms in cerebral ischemia. Journal of neurochemistry, 80(1), 12-23.
  3. 3. Silveri, M. M. Cognizin® Citicoline Increases Brain Energy (ATP) by 14% and Speeds up Formation of Brain Membranes by 26% in Healthy Adults. Soc. Neurosci, San Diego, CA.
  4. 4. Watanabe, S., Kono, S., Nakashima, Y., Mitsunobu, K., & Otsuki, S. (1975). Effects of various cerebral metabolic activators on glucose metabolism of brain. Folia psychiatrica et neurologica japonica, 29(1), 67-76.
  5. 5. Hurtado, O., Moro, M. A., Cárdenas, A., Sánchez, V., Fernández-Tomé, P., Leza, J. C., ... & Castillo, J. (2005). Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiology of disease, 18(2), 336-345.
  6. 6. Agut, J., & Wurtman, R. J. (1984). Cytidine (5') diphosphocholine enhances the ability of haloperidol to increase dopamine metabolites in the striatum of the rat and to diminish stereotyped behavior induced by apomorphine. Neuropharmacology, 23(12), 1403-1406.
  7. 7. Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats

L-Theanine
(125 mg)

Nootropic Description

L-theanine is a compound found in green tea that has synergistic properties with caffeine. It is unique in that it promotes relaxation without sedation by boosting alpha and theta brain waves. L-theanine also mildly increases GABA and catecholamine levels in the brain while preventing overstimulation and toxicity caused by glutamate. Users report senses of relaxation with a clean focus that is unlike that of a stimulant.

Supporting Studies

1. L-theanine administration encouraged alpha brain wave production in the occipital and parietal lobes of female subjects, causing relaxation

2. L-theanine mitigates the vasoconstrictive and behavioural effects of caffeine in levels and ratios equivalent to two cups of tea.

3. L-theanine reduces stress-induced hippocampal impairments of long-term potentiation and recognition memory in rats by modifying corticosterone secretion.

4. L-theanine intake resulted in a reduction in heart rate and salivary immunoglobulin responses during acute stress tasks. Measurements of the heart rate variability of subjects indicated that the reduction in heart rate was attributable to the decrease in sympathetic nervous activation. This suggests that L-theanine could decrease stress by inhibiting cortical neuron excitation.

5. L-theanine may reverse cognitive impairments and oxidative damage induced by chronic restraint stress in mice. This reversal is likely due to noticeable normalization of corticosterone serum and catecholamine levels in the serum and hippocampus.

Supporting Studies Citations

  1. 1. Kobayashi, K., Nagato, Y., Aoi, N., Juneja, L. R., Kim, M., Yamamoto, T., & Sugimoto, S. (1998). Effects of L-theanine on the release of alpha-brain waves in human volunteers. Journal of the Agricultural Chemical Society of Japan (Japan).
  2. 2. Dodd, F. L., Kennedy, D. O., Riby, L. M., & Haskell-Ramsay, C. F. (2015). A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood. Psychopharmacology, 232(14), 2563-2576.
  3. 3. Tamano, H., Fukura, K., Suzuki, M., Sakamoto, K., Yokogoshi, H., & Takeda, A. (2013). Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory. Brain research bulletin, 95, 1-6.
  4. 4. Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biological psychology, 74(1), 39-45.
  5. 5. Tian, X., Sun, L., Gou, L., Ling, X., Feng, Y., Wang, L., ... & Liu, Y. (2013). Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice. Brain research, 1503, 24-32.

American Ginseng
(125 mg)

Nootropic Description

American Ginseng, also known as Panax Quinquefolius, is known to improve mood, relieve stress, and improve brain energy. American Ginseng is rich in a variety of adaptogenic bioactive compounds studied for a range of unique long and short term effects. Individuals who supplement with ginseng report all-day increases in mental performance and concentration.

Supporting Studies

1. Preliminary study identified robust improvements in working memory performance associated Panax Quinquefolius along with improved reaction time accuracy and feelings of ‘calmness’

2. Visual spatial working memory and short-term memory where improved in individuals with schizophrenia when supplemented with panax quinquefolius containing known levels of active ginsenosides

3. Panax quinquefolium saponins protects low density lipoproteins from oxidation (anti-inflammatory) suggesting that the PQS extract improves the lipid profiles that are involved in the pathogenesis of atherosclerosis (hardening of artery walls)

4. Panax quinquefolium concurrently supplemented with ginkgo biloba may improve symptoms of ADHD in children ranging from 3 to 17 years old

5. Groups suffering from impaired cardiac function treated with panax quinquefolius improved the impaired cardiac structure and function, and decreased cardiomyocyte apoptosis

Supporting Studies Citations

  1. 1. Scholey, A., Ossoukhova, A., Owen, L., Ibarra, A., Pipingas, A., He, K., ... & Stough, C. (2010). Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomised, double-blind, placebo-controlled, crossover study. Psychopharmacology, 212(3), 345-356.
  2. 2. Chen, E. Y., & Hui, C. L. (2012). HT1001, a proprietary north American ginseng extract, improves working memory in schizophrenia: A double‐blind, placebo‐controlled study. Phytotherapy research, 26(8), 1166-1172.
  3. 3. Li, J., Huang, M., Teoh, H., & Man, R. Y. (1998). Panax quinquefolium saponins protects low density lipoproteins from oxidation. Life sciences, 64(1), 53-62.
  4. 4. Lyon, M. R., Cline, J. C., de Zepetnek, J. T., Shan, J. J., Pang, P., & Benishin, C. (2001). Effect of the herbal extract combination Panax quinquefolium and Ginkgo biloba on attention-deficit hyperactivity disorder: a pilot study. Journal of Psychiatry and Neuroscience, 26(3), 221.
  5. 5. Sun, H., Ling, S., Zhao, D., Li, Y., Zhong, G., Guo, M., ... & Li, J. (2019). Panax quinquefolium saponin attenuates cardiac remodeling induced by simulated microgravity. Phytomedicine, 56, 83-93.

Rhodiola Rosea
(100 mg; Standardized to 3% rosavins and 1% salidrosides)

Nootropic Description

Rhodiola Rosea is an adaptogenic herb that improves concentration and memory by reducing fatigue and anxiety. Rhodiola Rosea also stimulates neurogenesis by repairing and growing new neurons while protecting neurons from oxidative stress and apoptosis. Users who supplement with rhodiola rosea report significant reductions in both mental and physical fatigue with improvements in focus and mood.

Supporting Studies

1. Rhodiola rosea exhibits adaptogenic effects including neuroprotective, cardioprotective, anti-fatigue, antidepressive, anxiolytic, nootropic, life-span increasing effects and central nervous system stimulating activity. Repeated administration of Rhodiola rosea extract exerts an anti-fatigue effect that increases mental performance in healthy subjects, particularly the ability to concentrate, and reduces burnout in patients with fatigue syndrome.

2.By mitigating fatigue, supplementation of Rhodiola Rosea led to a statistically significant improvement in perceptive and cognitive cerebral functions among 56 physicians working night duty.

3. A randomized double-blind placebo-controlled parallel-group clinical study solidified rhodiola rosea as an adaptogen that attenuates fatigue and stress during mental work.

4. Rhodiola rosea may enhance the level of serotonin and promote the proliferation and differentiation of neural stem cells in the hippocampus of depressive rats. Rhodiola rosea may therefore play a role in saving injured neurons of the hippocampus.

5. A double-blind placebo-controlled study showed that Rhodiola Rosea led to significant reductions in depression, insomnia, emotional instability, and somatization compared to placebo.

Supporting Studies Citations

  1. 1. Panossian, A., Wikman, G., & Sarris, J. (2010). Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine, 17(7), 481-493.
  2. 2. Darbinyan, V., Kteyan, A., Panossian, A., Gabrielian, E., Wikman, G., & Wagner, H. (2000). Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine, 7(5), 365-371.
  3. 3. Shevtsov, V. A., Zholus, B. I., Shervarly, V. I., Vol'skij, V. B., Korovin, Y. P., Khristich, M. P., ... & Wikman, G. (2003). A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine, 10(2-3), 95-105.
  4. 4. Qin, Y. J., Zeng, Y. S., Zhou, C. C., Li, Y., & Zhong, Z. Q. (2008). Effects of Rhodiola rosea on level of 5-hydroxytryptamine, cell proliferation and differentiation, and number of neuron in cerebral hippocampus of rats with depression induced by chronic mild stress. Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi= China journal of Chinese materia medica, 33(23), 2842-2846.
  5. 5. Darbinyan, V., Aslanyan, G., Amroyan, E., Gabrielyan, E., Malmström, C., & Panossian, A. (2007). Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nordic journal of psychiatry, 61(5), 343-348.

Alpha-lipoic acid
(100 mg; as R-LA sodium salt)

Nootropic Description

Alpha-lipoic acid (ALA) is a powerful antioxidant that also assist in the production of cellular energy. ALA has the ability to cross the blood brain barrier giving it the ability to neutralize oxidative stress on neurons, especially after a stroke. ALA also regenerates endogenous antioxidants (Vitamins C & E, glutathione) and stimulates telomerase, the enzyme that lengthens telomeres.

Supporting Studies

1. Lipoic acid is carries out antioxidant activity within cells by repairing oxidative damage, regenerating endogenous antioxidants, and ability to scavenge reactive oxygen species.

2.Lipoic acid is a key cofactor in two enzymatic reactions in the Kreb’s Cycle, a reaction responsible for the creation of ATP.

3. Feeding ALCAR and/or ALA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function.

4. Emory University School of Medicine found that alpha lipoic acid can stimulate telomerase, the enzyme that lengthens telomeres, within a mouse model

5. Four year treatment with alpha lipoic acid in mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy resulted in a clinically meaningful improvement and prevention of progressive neuropathic impairments

6. Alpha lipoic acid appears to improve neuropathic symptoms and deficits when administered via parenteral supplementation over a 3-week period.

7. Benefits observed in glucose status with slight efficiency on oxidative stress-related deterioration in diabetes mellitus patients while effectively reducing HbA1c and blood glucose over a period of 6 months in persons with confirmed type 2 diabetes.

Supporting Studies Citations

  1. 1. Biewenga, G. P., Haenen, G. R., & Bast, A. (1997). The pharmacology of the antioxidant lipoic acid. General Pharmacology: The Vascular System, 29(3), 315-331.
  2. 2. Tomen, D., (2016, March 16). Start Here. Alpha-Lipoic Acid https://nootropicsexpert.com/alpha-lipoic-acid/#_edn8
  3. 3. Liu, J., Head, E., Gharib, A. M., Yuan, W., Ingersoll, R. T., Hagen, T. M., ... & Ames, B. N. (2002). Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-α-lipoic acid. Proceedings of the National Academy of Sciences, 99(4), 2356-2361.
  4. 4. Xiong, S., Patrushev, N., Forouzandeh, F., Hilenski, L., & Alexander, R. W. (2015). PGC-1α modulates telomere function and DNA damage in protecting against aging-related chronic diseases. Cell reports, 12(9), 1391-1399.
  5. 5. Ziegler, D., Low, P. A., Litchy, W. J., Boulton, A. J., Vinik, A. I., Freeman, R., ... & Schütte, K. (2011). Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes care, 34(9), 2054-2060.
  6. 6. Foster, T. S. (2007). Efficacy and safety of α-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy. The Diabetes Educator, 33(1), 111-117.
  7. 7. Porasuphatana, S., Suddee, S., Nartnampong, A., Konsil, J., Harnwong, B., & Santaweesuk, A. (2012). Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alphalipoic acid: a randomized double-blinded placebo-controlled study. Asia Pacific Journal of Clinical Nutrition, 21(1), 12-21.

Coenzyme Q10
(50 mg; as Ubiquinol)

Nootropic Description

Coenzyme Q10 is a naturally occurring nutrient in the body that helps fuel both neuronal and somatic mitochondria. Cells throughout the body utilize CoQ10 to transform carbohydrates and fats into useable energy for our bodies. CoQ10 also acts as a powerful antioxidant in conjunction with vitamins E, C, and selenium to prevent free radical damage. Individuals who supplement with CoQ10 report feelings of clarity and decreases in bodily fatigue.

Supporting Studies

1. Coenzyme Q10 served as a powerful antioxidant in mice, indicating its potential as a viable antioxidant strategy for neurodegenerative diseases like Alzheimer’s.

2.May play a role in treating neurodegenerative disorders by reducing mitochondrial oxidative stress

3. Supplementation of CoQ10 in pediatric and adolescent individuals suffering from migraines may result in clinical improvement

4. Water-soluble CoQ10 (ubiquinol) can prevent oxidative stress and neuronal damage induced by paraquat, and therefore can be used for the prevention and therapy of neurodegenerative diseases caused by environmental toxins.

5. Data suggests that ubiquinol has enhanced bioaccessibility and bioavailability in comparison to upiquinion resulting from easier incorporation during digestion.

6. Coenzyme Q10 appears to be quite effective at reducing the symptoms of fibromyalgia like fatigue and pain possibly through lipid peroxidation and pro-oxidation markers 60 days in a double-blind study displayed increases in VO2 max and decreased lactate production indicating improved exercise capacity

7. Supplementation with coenzyme 10 may improve endothelial cellular membranes enhancing cardiac function and blood flow

8. CoQ10 concentration levels are highest in organs with the highest rates of metabolism. Its primary biochemical action is to be a cofactor in the electron-transport chain when synthesizing ATP, while being a significant lipid antioxidant that prevents free radicals from negatively modifying proteins, lipids, and DNA.

Supporting Studies Citations

  1. 1. Wadsworth, T. L., Bishop, J. A., Pappu, A. S., Woltjer, R. L., & Quinn, J. F. (2008). Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease. Journal of Alzheimer's Disease, 14(2), 225-234.
  2. 2. Spindler, M., Beal, M. F., & Henchcliffe, C. (2009). Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatric disease and treatment, 5, 597.
  3. 3.Hershey, A. D., Powers, S. W., Vockell, A. L. B., LeCates, S. L., Ellinor, P. L., Segers, A., ... & Kabbouche, M. A. (2007). Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache: the journal of head and face pain, 47(1), 73-80.
  4. 4. Mcdonald, S. R., Sohal, R. S., & Forster, M. J. (2005). Concurrent administration of coenzyme Q10 and α-tocopherol improves learning in aged mice. Free Radical Biology and Medicine, 38(6), 729-736.
  5. 5. Failla, M. L., Chitchumroonchokchai, C., & Aoki, F. (2014). Increased bioavailability of ubiquinol compared to that of ubiquinone is due to more efficient micellarization during digestion and greater GSH-dependent uptake and basolateral secretion by Caco-2 cells. Journal of agricultural and food chemistry, 62(29), 7174-7182.
  6. 6. Glover, E. I., Martin, J., Maher, A., Thornhill, R. E., Moran, G. R., & Tarnopolsky, M. A. (2010). A randomized trial of coenzyme Q10 in mitochondrial disorders. Muscle & nerve, 42(5), 739-748.
  7. 7. Watts, G. F., Playford, D. A., Croft, K. D., Ward, N. C., Mori, T. A., & Burke, V. (2002). Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus. Diabetologia, 45(3), 420-426.
  8. 8. Dai, Y. L., Luk, T. H., Yiu, K. H., Wang, M., Yip, P. M., Lee, S. W., ... & Siu, C. W. (2011). Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial. Atherosclerosis, 216(2), 395-401.
  9. 9. Saini, R. (2011). Coenzyme Q10: the essential nutrient. J Pharm Bioallied Sci, 3(3), 466-467.

Celastrus Paniculatus Seed Extract
(50 mg)

Nootropic Description

Celastrus paniculatus is an herb used in Ayurvedic medicine that is known to increase cognition by protecting the brain from oxidative damage and neurotoxicity. Celastrus paniculatus has been observed to improve memory, learning and cognition while also serving as an antidepressant.

Supporting Studies

1. Supplementation of celastrus paniculatus, a powerful antioxidant, appeared to be highly effective in reducing immobilization stress induced oxidants in mice.

2.Pretreatment with celastrus paniculatus reduced the DNA fragmentation induced by aluminium neurotoxicity in the cerebral cortex, hippocampus, and cerebellum of the rat brain.

3. Celastrus paniculatus protected neurons from glutamate-induced death by modulating glutamate receptor function through augmented endogenous antioxidant enzymes and decreased lipid peroxidation in the rat brain.

4. Celastrus paniculatus seed oil produced significant antidepressant-like effects in mice possibly through interaction with dopamine D2, serotonergic, and GABAB receptors; as well as inhibition of MAO–A activity and decrease in plasma corticosterone levels.

Supporting Studies Citations

  1. 1. Lekha, G., Mohan, K., & Samy, I. A. (2010). Effect of Celastrus paniculatus seed oil (Jyothismati oil) on acute and chronic immobilization stress induced in swiss albino mice. Pharmacognosy research, 2(3), 169.
  2. 2. Bidwai, P., Wangoo, D., & Bhullar, N. (1987). Effect of Celastrus paniculatus seed extract on the brain of albino rats. Journal of Ethnopharmacology, 21(3), 307-314. doi:10.1016/0378-8741(87)90106-1
  3. 3. Godkar, P. B., Gordon, R. K., Ravindran, A., & Doctor, B. P. (2004). Celastrus paniculatus seed water soluble extracts protect against glutamate toxicity in neuronal cultures from rat forebrain. Journal of ethnopharmacology, 93(2-3), 213-219.
  4. 4. Valecha, R., & Dhingra, D. (2016). Behavioral and biochemical evidences for antidepressant-like activity of Celastrus paniculatus seed oil in mice. Basic and clinical neuroscience, 7(1), 49.

Coleus Forskohlii
(10 mg; Standardized to 20% Forskolin))

Nootropic Description

Forskohlii has been used in traditional Hindu medicine and is known to naturally boost cAMP (Cyclic Adenosine Monophosphate) and BDNF (brain derived ` neurotrophic factor) increasing synaptic plasticity. These mechanisms encourage long-term potentiation while increasing cerebral blood flow, positively influencing cognition and memory formation. Users that supplement with forskohlii report improvements in general cognition, mood, and energy levels.

Supporting Studies

1. The elevation of cAMP levels increased brain-derived neurotrophic factor which activates protein kinase leading to long-term potentiation within the hippocampus.

2.Forskolin is a direct cerebral vasodilator, but does not potentiate cerebral vasodilation in response to adenosine.

3. Long-term potentiation, an indirect result of forskohlii supplementation, is a well studied form a neuroplasticity and correlates with memory formation.

4. Increased concentrations of cAMP, triggered by forskohlii supplementation, activates CREB, a protein involved in memory formation.

Supporting Studies Citations

  1. 1. Patterson, S. L., Pittenger, C., Morozov, A., Martin, K. C., Scanlin, H., Drake, C., & Kandel, E. R. (2001). Some forms of cAMP-mediated long-lasting potentiation are associated with release of BDNF and nuclear translocation of phospho-MAP kinase. Neuron, 32(1), 123-140.
  2. 2. Wysham, D. G., Brotherton, A. F., & Heistad, D. D. (1986). Effects of forskolin on cerebral blood flow: implications for a role of adenylate cyclase. Stroke, 17(6), 1299-1303.
  3. 3. Cooke, S. F., & Bliss, T. V. P. (2006). Plasticity in the human central nervous system. Brain, 129(7), 1659-1673.
  4. 4. Silva, A. J., Kogan, J. H., Frankland, P. W., & Kida, S. (1998). CREB and memory. Annual review of neuroscience, 21(1), 127-148.

Cannabidiol
(5mg; as 99% CBD Isolate from Hemp)

Nootropic Description

Beneficial effects of CBD have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. In addition to CBD's many mood regulating benefits, it has also been shown to improve the brain’s health and functional efficiency by reducing neuronal loss, increasing brain derived neurotrophic factor, and enhancing dendritic development.

Supporting Studies

1. Chronic treatment with cannabidiol at a dose of 15 mg/kg and imipramine at a dose of 30mg/kg increased BDNF levels in rat amygdalas.

2. CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress, and modulates cell fate regulatory pathways like autophagy critical for neuronal survival in neurodegenerative experimental models.

3. CBD administration after middle cerebral artery occlusion led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation.

4. Treatment with a high dose of CBD 100mg/kg or a low dose of 10mg/kg elicited significant antidepressant-like behavioral effects in forced swim test, following increased mRNA expression of brain-derived neurotrophic factor and synaptophysin in the prefrontal cortex and hippocampus.

5. CBD may be used as a pharmacological tool to improve neurological dysfunctions caused by trauma by positively modifying the behavioral phenotype associated with traumatic brain injuries

6. By increasing brain derived neurotrophic factor signaling and synaptogenesis in the prefrontal cortex, cannabidiol induces rapid and sustained antidepressant-like effects

7. Cannabidiol treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus and prefrontal cortex demonstrating CBD’s neuroprotective properties

8. Short-term cannabidiol treatment in mice with bilateral common carotid artery occlusion increased hippocampal brain derived neurotrophic factor, neurogenesis, and dendritic restructuring while attenuating hippocampal neurodegeneration and reducing gliosis

Supporting Studies Citations

  1. 1. Réus, G. Z., Stringari, R. B., Ribeiro, K. F., Luft, T., Abelaira, H. M., Fries, G. R., ... & Crippa, J. A. (2011). Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala. Acta neuropsychiatrica, 23(5), 241-248.
  2. 2. Réus, G. Z., Stringari, R. B., Ribeiro, K. F., Luft, T., Abelaira, H. M., Fries, G. R., ... & Crippa, J. A. (2011). Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala. Acta neuropsychiatrica, 23(5), 241-248.
  3. 3. Ceprián, M., Jiménez-Sánchez, L., Vargas, C., Barata, L., Hind, W., & Martínez-Orgado, J. (2017). Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke. Neuropharmacology, 116, 151-159.
  4. 4. Xu, C., Chang, T., Du, Y., Yu, C., Tan, X., & Li, X. (2019). Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model. Environmental toxicology and pharmacology, 103202.
  5. 5. Belardo, C., Iannotta, M., Boccella, S., Rubino, R. C., Ricciardi, F., Infantino, R., . . . Guida, F. (2019). Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury. Frontiers in Pharmacology, 10. doi:10.3389/fphar.2019.00352
  6. 6. Sales, A. J., Fogaça, M. V., Sartim, A. G., Pereira, V. S., Wegener, G., Guimarães, F. S., & Joca, S. R. (2019). Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Molecular neurobiology, 56(2), 1070-1081.
  7. 7. Campos, A. C. D., Brant, F., Miranda, A. S., Machado, F. S., & Teixeira, A. L. (2015). Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria. Neuroscience, 289, 166-180.
  8. 8. Mori, M. A., Meyer, E., Soares, L. M., Milani, H., Guimarães, F. S., & de Oliveira, R. M. W. (2017). Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 75, 94-105.

Pyrroloquinoline Quinone
(5 mg)

Nootropic Description

Clinical research on humans indicates that Pyrroloquinoline Quinone (PQQ) is the only known nutrient to facilitate mitochondrial production in brain cells. It is known to stimulate the production of nerve growth factor (NGF), boosting memory, learning, and cognition. PQQ also acts as an anti-inflammatory agent by reducing glutamate-induced toxicity preventing cellular death or apoptosis. When taken as a supplement users tend to report improvements in both mental and physical energy levels permitting elevated concentration.

Supporting Studies

1. PQQ reprogrammed mitochondrial oxygen consumption rate (OCR) leading to increased glycolytic metabolism. PQQ also highly enhanced the expression of oxidative fibers maintained by the type II glycolytic fibers making it a potentially potent therapeutic benefit for denervation-induced atrophy.

2. PQQ conferred neuroprotection to participants with rotenone-induced Parkinson’s disease, reducing apoptosis, inhibiting intracellular reactive oxygen species, and restoring mitochondrial membrane potential

3. PQQ stimulated cell proliferation and reduced glutamate-induced cell damage and apoptosis. PQQ supplementation was associated with a decrease in intracellular reactive oxygen species, an increase in the powerful antioxidant glutathione, and a decrease in apoptosis.

4. PQQ supplementation is related to cognitive, immune, and antioxidant functions. It is particularly important in mitochondriogenesis.

5. PQQ suppressed the low-density lipoprotein cholesterol levels which may decrease the risk of clogged arteries, heart disease, and stroke.

Supporting Studies Citations

  1. 1. Kuo, Y. T., Shih, P. H., Kao, S. H., Yeh, G. C., & Lee, H. M. (2015). Pyrroloquinoline Quinone Resists Denervation-Induced Skeletal Muscle Atrophy by Activating PGC-1α and Integrating Mitochondrial Electron Transport Chain Complexes. PloS one, 10(12), e0143600.
  2. 2. Qin, J., Wu, M., Yu, S., Gao, X., Zhang, J., Dong, X., ... & Ding, F. (2015). Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson’s disease. Toxicology letters, 238(3), 70-82.
  3. 3. Guan, S., Xu, J., Guo, Y., Ge, D., Liu, T., Ma, X., & Cui, Z. (2015). Pyrroloquinoline quinone against glutamate-induced neurotoxicity in cultured neural stem and progenitor cells. International Journal of Developmental Neuroscience, 42, 37-45.
  4. 4. Rucker, R., Chowanadisai, W., & Nakano, M. (2009). Potential physiological importance of pyrroloquinoline quinone. Alternative Medicine Review, 14(3), 268.
  5. 5. Rucker, R., Chowanadisai, W., & Nakano, M. (2009). Potential physiological importance of pyrroloquinoline quinone. Alternative Medicine Review, 14(3), 268.
  6. 6. Nakano, M., Kawasaki, Y., Suzuki, N., & Takara, T. (2015). Effects of pyrroloquinoline quinone disodium salt intake on the serum cholesterol levels of healthy Japanese adults. Journal of nutritional science and vitaminology, 61(3), 233-240.

Nicotinamide Adenine Dinucleotide
(5 mg; as PANMOL)

Nootropic Description

NADH protects brain cells by repairing DNA damage and acting as an antioxidant. NADH indirectly relaxes blood vessels by boosting the production of nitric oxide which increases blood flow to the brain. It also provides electrons for ATP synthesis, fueling mitochondria in both brain and body cells and increasing clarity and cognition. Neurotransmitters like dopamine, norepinephrine, and serotonin are stimulated by NADH affecting memory, learning, cognition, recall, and mood. Users report acute increases in mental energy levels along with elevated mood and cognition.

Supporting Studies

1. NADH and NAD+ reduce the neuronal death responsible for many neurological diseases by mediating energy metabolism, mitochondrial functions, and calcium homeostasis. Supplementation seems to also profoundly decrease ischemic brain damage.

2. NADH and NAD+ play important roles in neurotransmission for learning and memory while attenuating brain aging and tissue damage.

3. Supplementation of NADH was associated with a decrease in anxiety and maximum heart rate in stress tests in patients with chronic fatigue syndrome.

4. Concurrent supplementation of NADH and Coenzyme 10 led to a statistically significant reduction in fatigue for patients with chronic fatigue syndrome.

Supporting Studies Citations

  1. 1. Ying, W. (2007). NAD and NADH in Neuronal Death. Journal of Neuroimmune Pharmacology, 2(3), 270-275. doi:10.1007/s11481-007-9063-5
  2. 2. Ying, W. (2007). NAD+ and NADH in brain functions, brain diseases and brain aging. Frontiers in bioscience: a journal and virtual library, 12, 1863-1888.
  3. 3. Alegre, J., Rosés, J. M., Javierre, C., Ruiz-Baqués, A., & Segundo, M. J. (2010). Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome. Revista clinica espanola, 210(6), 284-288.
  4. 4. Santaella, M. L., Font, I., & Disdier, O. M. (2004). Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. Puerto Rico health sciences journal, 23(2).
  5. 5. Castro-Marrero, J., Cordero, M. D., Segundo, M. J., Sáez-Francas, N., Calvo, N., Román-Malo, L., ... & Alegre, J. (2015). Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?. (679-685).

B6
(5 mg; as Pyridoxal 5’-Phosphate)

Nootropic Description

The active form of vitamin B6 is recognized as one of the most versatile organic cofactors in the body contributing to over 140 enzymatic activities. In particular, vitamin B6 acts as a cofactor for neurotransmitters like dopamine, epinephrine, GABA, norepinephrine, and serotonin. These neurotransmitters each contribute to improvements in memory, focus, cognition, and mood regulation. Deficient users that supplement vitamin B6 report changes in mood such as reduced anxiety or depression and elevated energy levels.

Supporting Studies

1. Pyridoxal phosphate is a cofactor involved in over 100 enzyme-catalysed reactions in the body, including many involved in the synthesis or catabolism of neurotransmitters. Inadequate levels of pyridoxal phosphate in the brain cause neurological dysfunction.

2. Plasma pyridoxal-5-phosphate (B6) is inversely associated with systemic markers of inflammation in a population of U.S. adults.

3. Supplementation of folic acid, B6, and B12 can slow atrophy of specific brain regions that are associated with cognitive decline and are key components of the Alzheimer’s Disease process.

4. A significant proportion of populations in developed countries suffer from deficiencies or insufficiencies in one or more B-vitamins despite their importance in energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and synthesis of neurochemicals and signaling molecules.

Supporting Studies Citations

  1. 1. Clayton, P. T. (2006). B 6-responsive disorders: a model of vitamin dependency. Journal of inherited metabolic disease, 29(2-3), 317-326.
  2. 2. Sakakeeny, L., Roubenoff, R., Obin, M., Fontes, J. D., Benjamin, E. J., Bujanover, Y., ... & Selhub, J. (2012). Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of US adults. The Journal of nutrition, 142(7), 1280-1285.
  3. 3. Douaud, G., Refsum, H., de Jager, C. A., Jacoby, R., Nichols, T. E., Smith, S. M., & Smith, A. D. (2013). Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences, 110(23), 9523-9528.
  4. 4. Kennedy, D. (2016). B vitamins and the brain: mechanisms, dose and efficacy—a review. Nutrients, 8(2), 68.