THIS MEDICAL AND SCIENTIFIC INFORMATION IS PROVIDED FOR THE USE OF PHYSICIANS AND OTHER LICENSED HEALTH CARE PRACTITIONERS ONLY TO USE AS A BASIS FOR DETERMINING WHETHER OR NOT TO RECOMMEND THESE PRODUCTS TO THEIR PATIENTS. THIS INFORMATION IS NOT FOR USE BY CONSUMERS. THE PRODUCTS DESCRIBED HERE ARE NOT INTENDED FOR USE BY CONSUMERS AS A MEANS TO CURE, TREAT, PREVENT, DIAGNOSE, OR MITIGATE ANY DISEASE OR MEDICAL CONDITION.
Overview
As men age, cognitive decline becomes a growing concern. Studies indicate that after age 50, many men begin to experience a gradual reduction in cognitive abilities, including memory, attention, and the speed at which they process information. By age 65, approximately 22% of men face some form of mild cognitive impairment (MCI)—a condition that bridges the gap between normal aging and dementia. By age 70, difficulties with focus, problem-solving, and multitasking become even more prevalent.
This cognitive decline can significantly impact both work performance and daily life, affecting decision-making, memory recall, and overall productivity. As the ability to perform effectively diminishes, many men experience frustration, which can spiral into feelings of inadequacy and, in some cases, lead to depression. Addressing cognitive health early on is crucial to maintaining well-being and performance as we age.
Understanding the Causes of Cognitive decline, Mood swings and Low energy with Aging
Why cognitive decline, low energy and a general feeling of the blues occur in men as they age are complex and interconnected, involving multiple systems, including the brain, hormones, and cellular energy processes.
As men age, key neurotransmitters such as acetylcholine (important for memory), dopamine (vital for motivation and reward), serotonin, and norepinephrine—which regulate mood, pleasure, and motivation—gradually decline. This, combined with oxidative damage to the brain, lower functional testosterone, and chronic low-level inflammation, contributes to cognitive decline and reduced energy. These factors impair memory, attention, and overall mood. Here’s how:
Inflammation:Elevated levels of pro-inflammatory cytokines, such as IL-6 and TNF-alpha, are linked to both depression and cognitive decline, supporting the "inflammatory model of depression."
Low Functional Testosterone:Free, bioavailable testosterone plays a crucial neuroprotective role and enhances mood. Low levels of free testosterone contribute to reduced energy, mood swings, depression, decreased motivation, and cognitive impairments. The concept of "functional testosterone" goes beyond total testosterone levels—it emphasizes optimizing bioavailable testosterone, maintaining a healthy testosterone-to-estrogen ratio, and ensuring androgen receptor health to fully realize the benefits of testosterone.
High Cortisol:The hypothalamic-pituitary-adrenal (HPA) axis, which regulates stress responses, becomes dysregulated with age, leading to chronically elevated cortisol levels. Prolonged high cortisol exposure can damage the hippocampus, a brain region critical for memory, and contribute to mood disorders like depression.
Mitochondrial Dysfunction:Mitochondria, the "powerhouses" of cells that produce ATP, become less efficient as we age, leading to fatigue and low energy levels, further compounding the effects of aging on cognitive function and mood.
Reduced Neuroplasticity:Neuroplasticity refers to the brain’s ability to adapt and form new connections. Aging leads to a decline in neuroplasticity, limiting the brain’s ability to learn new information and adapt to new situations.
Strategies to Combat Aging Brain and Body
A combination of lifestyle interventions–exercise, healthy diet, and adequate sleep– and targeted supplements with vitamins, minerals, and botanicals such as those found in Better with Age can provide the brain with the necessary nutrients to support cognitive function, mood, and energy, helping to counteract some of the biochemical changes associated with aging.
A Unique and Focused Dietary Supplement– Mr. Happy Better with Age
Mr. Happy Better with Age is a carefully developed formula by Dr. Geo Espinosa to optimized memory, alertness, and improved mood. This carefully developed formula contain the most essential botanicals and nutrients for men to function biologically younger than their calendar years.
How Does Mr. Happy Better with Age Work
Better with Age is a comprehensive vitamin, mineral and botanical formula designed to enhance mood, cognition, and energy through a synergistic blend of natural ingredients. *
Curcumin (Curcuma longa)
Curcumin, the active component in turmeric, has been shown to improve working memory, reduce fatigue, and enhance mood by alleviating stress and tension, particularly in older adults . Its potent anti-inflammatory and antioxidant properties help protect the brain from oxidative damage, a key factor in cognitive decline. Curcumin is able to cross the blood-brain barrier, where it increases levels of brain-derived neurotrophic factor (BDNF), a protein that supports neuroplasticity and overall cognitive function. Additionally, curcumin boosts serotonin and dopamine levels, neurotransmitters that regulate mood and help combat depression . By reducing oxidative stress in mitochondria, curcumin also supports cellular energy production, contributing to improved mental and physical vitality.
Folate, Vitamin B6, Vitamin 12: The active forms of folate (L-5-methyltetrahydrofolate – L-5-MTHF), Vitamin B6 (Pyridoxal 5’-Phosphate - P5P), and Vitamin B12 (Methylcobalamin) are more effective than their synthetic counterparts because they bypass conversion steps, are more bioavailable, and work synergistically to enhance cognition and mood.
These essential nutrients play crucial and interconnected roles in lowering homocysteine levels, a known risk factor for cardiovascular disease, cognitive decline, and mood disorders. These B vitamins are involved in key biochemical pathways that lead to significant improvements in cognition, energy, and mood. Adequate levels of folate, B6, and B12 are essential for the proper metabolism of homocysteine. Elevated homocysteine levels are linked to an increased risk of cardiovascular disease, dementia, Alzheimer’s disease, and mood disorders like depression. By lowering homocysteine, these vitamins help protect cognitive function and reduce the risk of cognitive impairment.
Lastly, the methylation process, supported by folate and B12, is crucial for the production of neurotransmitters such as serotonin, dopamine, and norepinephrine—key regulators of mood, cognition, and memory.
Vitamin C (Ascorbic Acid)
Vitamin C improves mood and reduces stress by supporting the production of dopamine, a neurotransmitter responsible for reward, motivation, and pleasure. It also acts as a cofactor in the conversion of dopamine to norepinephrine, a neurotransmitter crucial for attention, stress response, and mood regulation. Adequate levels of norepinephrine are associated with improved mood and reduced symptoms of depression. Additionally, Vitamin C helps regulate cortisol, the hormone released during stress. High cortisol levels can lead to mood disturbances, increased anxiety, and lower testosterone levels. By reducing cortisol, Vitamin C indirectly supports testosterone production, which is essential for maintaining energy, motivation, and vitality in men. Chronic high cortisol levels can suppress testosterone, leading to fatigue and reduced energy.
Several studies suggest that higher vitamin C intake is linked to better cognitive performance and a reduced risk of cognitive decline, particularly in aging populations. This may be due to its antioxidant properties and its role in neurotransmitter regulation. Lastly, Vitamin C is involved in the synthesis of carnitine, a molecule necessary for the transport of fatty acids into mitochondria, where they are converted into energy. This process is critical for maintaining both physical and mental energy, and a deficiency in vitamin C has been linked to fatigue and low energy levels.
Vitamin D3
Vitamin D receptors are located throughout the brain, particularly in regions involved in mood regulation and cognitive function, such as the hippocampus and prefrontal cortex. Adequate levels of vitamin D are crucial for promoting serotonin production, a neurotransmitter that enhances mood and mental clarity. Research consistently links low levels of vitamin D with an increased risk of depression and cognitive decline. Additionally, vitamin D plays a vital role in supporting healthy testosterone levels, which contributes to improved energy, mood, and cognitive function.
Velvet Bean (Mucuna Pruriens)
Velvet bean contains L-DOPA, a direct precursor to dopamine, which plays a key role in enhancing mood, motivation, and cognitive function . By increasing dopamine levels, Mucuna pruriens has been shown to improve symptoms of depression and boost overall mental performance. Additionally, research indicates that Mucuna pruriens improves testosterone levels and fertility by reducing oxidative stress and enhancing testosterone production, contributing to improved reproductive health and vitality.
L-Theanine
L-Theanine, an amino acid found in tea, promotes relaxation without causing sedation by increasing levels of key neurotransmitters such as GABA, serotonin, and dopamine . This modulation of brain chemistry leads to a calm state of focus, enhanced mental clarity, and reduced stress. Additionally, L-Theanine increases alpha brainwave activity, which is associated with a relaxed yet alert mental state, further promoting concentration and focus . Research has shown that L-Theanine improves attention and working memory by reducing cognitive interference and promoting relaxation. This allows for better cognitive performance, especially in tasks that require sustained focus and mental flexibility.
Lion’s mane mushrooms (Hericium erinaceus)
Lion’s Mane mushroom stimulates the production of nerve growth factor (NGF), a protein essential for the growth, maintenance, and survival of neurons. By promoting neurogenesis, Lion’s Mane enhances brain function, supporting improved memory, cognitive function, and neuroplasticity. Studies have linked Lion’s Mane to better cognitive performance, particularly in areas like learning and memory. Lion’s Mane also exhibits strong anti-inflammatory and antioxidant properties, which help protect brain cells from oxidative stress and neuroinflammation, both of which are implicated in mood disorders and cognitive decline . Research suggests that Lion’s Mane can reduce symptoms of anxiety and depression, likely due to its ability to modulate inflammation and improve overall brain health. By supporting nerve health and reducing oxidative stress, Lion’s Mane contributes to increased mental clarity and sustained energy levels, helping combat mental fatigue and promoting a sense of well-being.
Huperzine A
Huperzine A, a natural compound from the Chinese club moss (Huperzia serrata), works by blocking the enzyme acetylcholinesterase, which breaks down acetylcholine—a neurotransmitter essential for learning and memory. By preserving acetylcholine levels, Huperzine A improves cognitive functions like memory, focus, and mental clarity. It is particularly beneficial in supporting brain health, as higher acetylcholine levels help maintain sharper cognitive performance, especially in aging individuals or those experiencing cognitive decline.
Additionally, Huperzine A has neuroprotective effects, helping to reduce oxidative stress and inflammation in the brain, which are linked to cognitive impairment. Its ability to protect neurons also contributes to mood regulation, potentially reducing symptoms of anxiety and depression by supporting overall brain function.
Ashwagandha (Withania somnifera)
Ashwagandha is a powerful adaptogen, meaning it helps the body adapt to stress by regulating cortisol, the hormone released during stressful situations. By modulating cortisol levels, ashwagandha reduces stress, alleviates anxiety, and enhances overall mood. Research shows that ashwagandha also improves cognitive function by promoting mental clarity and reducing anxiety. Ashwagandha has been shown to boost testosterone levels, which can lead to improved energy, motivation, and mood. Increased testosterone is linked to better physical vitality and mental well-being, making ashwagandha an effective supplement for supporting both energy levels and overall performance in men.
Bacopa Monnieri
Bacopa is a nootropic herb known for its ability to enhance memory and learning by promoting dendritic growth, which strengthens the connections between neurons and improves communication within the brain. This supports cognitive functions like memory retention and learning . Bacopa also increases levels of serotonin and GABA, two neurotransmitters that play crucial roles in mood regulation. By boosting these neurotransmitters, Bacopa helps reduce anxiety and improve overall mood . Additionally, Bacopa has strong antioxidant properties, which protect the brain from oxidative stress and damage caused by free radicals. This protection helps preserve brain health over time, supporting long-term cognitive function and reducing the risk of age-related cognitive decline.
Acetyl-L-Carnitine
Acetyl-L-carnitine plays a crucial role in energy production by transporting fatty acids into the mitochondria, where they are converted into ATP—the body’s primary energy source. This process boosts both physical and mental energy level. Acetyl-L-carnitine also enhances mitochondrial function, improving cellular energy efficiency and reducing oxidative stress, which protects the brain from age-related decline. In addition, Acetyl-L-carnitine supports the production of acetylcholine, a neurotransmitter essential for memory and cognitive function. By promoting acetylcholine synthesis, Acetyl-L-carnitine helps improve memory retention, learning, and overall cognitive performance. It also has neuroprotective effects, helping to preserve brain health, and it enhances mood by stimulating dopamine release, which is linked to motivation, reward, and emotional well-being.
Magnesium Glycinate
Magnesium Glycinateis a highly bioavailable form of magnesium, offering significant benefits for cognitive health, mood, testosterone levels, and energy production. Magnesium supports synaptic plasticity, essential for learning and memory, and low levels are linked to cognitive decline. By increasing magnesium availability in the brain, magnesium glycinate can enhance memory, learning, and overall cognitive performance.
Magnesium also plays a crucial role in mood regulation by boosting neurotransmitter levels, such as serotonin, and modulating the hypothalamic-pituitary-adrenal (HPA) axis to reduce stress and anxiety. Research shows that magnesium supplementation helps alleviate symptoms of depression, particularly when magnesium levels are low. Additionally, magnesium has been shown to positively influence testosterone levels, especially in physically active individuals, by increasing free testosterone availability and supporting anabolic processes, leading to improved energy, motivation, and mood.
As a cofactor in ATP production, magnesium is essential for mitochondrial function and energy metabolism. Magnesium glycinate helps optimize cellular energy production, reduce fatigue, and protect mitochondria from oxidative stress, contributing to better overall metabolic health.
The Interconnectedness of Cognitive Decline, Depression, and Low Energy
Many biological systems involved in cognitive function, mood regulation, and energy production are deeply interconnected, so a decline in one area can often trigger or exacerbate problems in others. For instance, reduced cognitive function often leads to frustration and negative emotions, increasing the risk of depression. Similarly, low energy and fatigue—resulting from mitochondrial dysfunction or hormonal imbalances—diminish motivation and mental sharpness, feeding into a cycle of cognitive decline and mood disorders. Chronic stress and elevated cortisol levels worsen these conditions by damaging brain cells, impairing sleep, and reducing testosterone levels, creating a vicious cycle of cognitive impairment, low energy, and depression.
Holistic, Science-Backed Solutions for a Complex Problem
Addressing an aging brain and the associated mood and energy decline requires a comprehensive, multifaceted approach. Think of it like addressing a complex system—similar to repairing the interconnected parts of an engine—where improving one component (e.g., energy production) can positively affect others (e.g., cognitive sharpness). Solutions need to be holistic and grounded in science, targeting multiple pathways simultaneously. Optimizing diet, regular exercise, sufficient sleep, and targeted supplementation are foundational strategies that can slow, and in some cases, potentially reverse brain aging. Each of these interventions helps to restore functional testosterone levels, reduce oxidative stress, support mitochondrial function, and promote neuroplasticity, leading to improvements in cognition, mood, and energy.
Summary on How Mr. Happy Better with Age work
These nutrients and botanicals work synergistically to support mood, cognitive function, memory, and energy by:
- Enhancing neurotransmitter production and balance (serotonin, dopamine, acetylcholine).*
- Supporting mitochondrial function for energy production.*
- Optimizing testosterone levels and androgen receptor health.*
- Reducing inflammation and oxidative stress, which are key contributors to cognitive decline, mood disorders, and fatigue.*
Product Information:
90 capsules per bottle
Quality Assurance: Manufactured in a GMP-registered facility in the U.S.A.
Recommended Use: Adults take three (3) capsules once or twice a day or as directed by your by your healthcare practitioner.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
Reference:
Overview
1.Cai X, et.al. (2024).The effects of exergames for cognitive function in older adults with mild cognitive impairment: a systematic review and metaanalysis. Front Neurol. Jul 16;15:1424390. doi: 10.3389/fneur.2024.1424390.
2.Fotenos AF, et.al. (2008). Brain Volume Decline in Aging:Evidence for a Relation Between Socioeconomic Status, Preclinical Alzheimer Disease, and Reserve.Arch Neurol.;65(1):113–120.
3.Statsenko Y, et.al. (2022).Brain Morphometry and Cognitive Performance in Normal Brain Aging: Age- and Sex-Related Structural and Functional Changes. Front Aging Neurosci. Jan 26;13:713680.
4.Geda, Y.E. (2012). Mild Cognitive Impairment in Older Adults.Curr Psychiatry Rep14, 320–327
Curcumin
1.Cox, K. H., et al. (2015). The effects of turmeric (curcumin) on brain function in older adults: A randomized, placebo-controlled trial. Journal of Psychopharmacology, 29(5), 642-651.
2.Aggarwal, B. B., & Harikumar, K. B. (2009). Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune, and neoplastic diseases. The International Journal of Biochemistry & Cell Biology, 41(1), 40-59.
3.Kulkarni, S. K., & Dhir, A. (2010). An overview of curcumin in neurological disorders. Indian Journal of Pharmaceutical Sciences, 72(2), 149-154.
4.Jurenka, J. S. (2009). Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Alternative Medicine Review, 14(2), 141-153.
5.Sarraf P., et al. (2019). Short-term curcumin supplementation enhances serum brain-derived neurotrophic factor in adult men and women: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutr Res.Sep;69:1-8.
6.Sathyabhama M., (2022). The Credible Role of Curcumin in Oxidative Stress-Mediated Mitochondrial Dysfunction in Mammals. Biomolecules. 2022 Oct 1;12(10):1405.
7.Rainey NE., et al. (2020). Hormetic Agent, Mediates an Intricate Crosstalk between Mitochondrial Turnover, Autophagy, and Apoptosis. Oxid Med Cell Longev. 2020 Jul 18;2020:3656419.
8.Nunes YC., et. al. (2024) Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence. Nutrients. 2024 Aug 15;16(16):2721.
9.Seddon N., et al. (2019) Effects of curcumin on cognitive function—A systematic review of randomized controlled trials. Explor. Res. Hypothesis Med. 2019;4:1–11.
10.Small G.W. et al. (2018) Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: A double-blind, placebo-controlled 18-month trial. Am. J. Geriatr. Psychiatry.;26:266–277.
Folate, Vitamin B6, Vitamin 12
1.Carboni L. Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health. Integr Med (Encinitas). 2022 Jul;21(3):36-41. PMID: 35999905; PMCID: PMC9380836.
2.Fava M, Mischoulon D. Folate in depression: efficacy, safety, differences in formulations, and clinical issues. J Clin Psychiatry. 2009;70 Suppl 5:12-7. doi: 10.4088/JCP.8157su1c.03. PMID: 19909688.
3.Field DT, Cracknell RO, Eastwood JR, Scarfe P, Williams CM, Zheng Y, Tavassoli T. High-dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression. Hum Psychopharmacol. 2022 Nov;37(6):e2852. doi: 10.1002/hup.2852. Epub 2022 Jul 19. PMID: 35851507; PMCID: PMC9787829.
4.Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. Nutrients. 2016 Jan 27;8(2):68. doi: 10.3390/nu8020068. PMID: 26828517; PMCID: PMC4772032.
5.Stach K, Stach W, Augoff K. Vitamin B6 in Health and Disease. Nutrients. 2021 Sep 17;13(9):3229. doi: 10.3390/nu13093229. PMID: 34579110; PMCID: PMC8467949.
6.Song Y, Quan M, Li T, Jia J. Serum Homocysteine, Vitamin B12, Folate, and Their Association with Mild Cognitive Impairment and Subtypes of Dementia. J Alzheimers Dis. 2022;90(2):681-691. doi: 10.3233/JAD-220410. PMID: 36155508.
7.Smith, A. D., Refsum, H. (2016). Homocysteine, B Vitamins, and Cognitive Impairment. Annual Review of Nutrition, 36, 211–239.
8.Stanger, O., Fowler, B., Piertzik, K. (2009). Homocysteine, folate and vitamin B12 in neuropsychiatric disorders: Review and treatment recommendations. Expert Review of Neurotherapeutics, 9(9), 1393–1412.
9.Van Dam, F., Van Gool, W. A. (2009). Hyperhomocysteinemia and Alzheimer’s disease: A systematic review. Archives of Gerontology and Geriatrics, 48(3), 425–430.
10.Moore, E. M., Ames, D., Mander, A. G., et al. (2014). Among B vitamins, lower homocysteine to prevent cognitive decline in older adults: A randomized clinical trial. Neurology, 82(11), 909–916.
11.Reynolds, E. (2006). Vitamin B12, folic acid, and the nervous system. The Lancet Neurology, 5(11), 949-960.
12.Pokushalov E et al.Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial. Nutrients. 2024 May 21;16(11):1550.
13.Lam NSK et al.The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review. Biomed Pharmacother. 2022 Feb;146:112541. doi: 10.1016/j.biopha.2021.112541. Epub 2021 Dec 22. PMID: 34953391.
14.Akhgarjand C et al.Does folic acid supplementation have a positive effect on improving memory? A systematic review and meta-analysis of randomized controlled trials. Front Aging Neurosci. 2022 Nov 28;14:966933.
Vitamin C
1.May, J. M. (2012). Vitamin C transport and its role in the central nervous system. Subcellular Biochemistry, 56, 85-103.
2.Hansen, S. N., et al. (2017). Vitamin C deficiency reduces the levels of noradrenaline in the locus coeruleus and impairs memory. BMC Neuroscience, 18(1), 24.
3.Moretti, M., et al. (2013). Role of vitamin C in preventing neurodegeneration and modulating neurotransmitter homeostasis. Neuroscience Letters, 539, 82-86.
4.Brody, S. (2002). High-dose ascorbic acid increases intercourse frequency and improves mood: A randomized controlled clinical trial. Biological Psychiatry, 52(4), 371-374.
5.Talbott, S. M., & Talbott, J. A. (2012). Effect of ascorbic acid supplementation on cortisol and psychomotor performance following exhaustive exercise. The FASEB Journal, 26(S1), 1067-1067.
6.Harrison, F. E., & May, J. M. (2009). Vitamin C function in the brain: Vital role of the ascorbate transporter SVCT2. Free Radical Biology and Medicine, 46(6), 719-730.
7.Nicolas, M., et al. (2013). Vitamin C deficiency alters brain monoamine levels in dopamine-rich areas and is associated with impaired spatial memory function in male and female vitamin C-deficient mice. Journal of Nutrition and Food Sciences, 1-8.
8.Karakis, I., et al. (2016). Association of serum vitamin C levels with cognitive function and brain volume in older adults. JAMA Neurology, 73(2), 149-156.
9.Jacob, R. A., et al. (1996). Vitamin C status and mood state in young males: Effect of ascorbate depletion and supplementation. Nutrition Reports International, 35(2), 199-210.
10.McGregor, G. P., & Biesalski, H. K. (2006). Rationale and impact of vitamin C in clinical nutrition. Current Opinion in Clinical Nutrition & Metabolic Care, 9(6), 697-703.
11.Booth, A., et al. (2007). Testosterone and social behavior. Social Forces, 85(1), 167-191.
12.Maggio, M., et al. (2009). The interplay between testosterone and cortisol in cognitive aging: A review. Current Pharmaceutical Design, 15(30), 3529-3542.
13.Sim M et al. (2022). Vitamin C supplementation promotes mental vitality in healthy young adults: results from a cross-sectional analysis and a randomized, double-blind, placebo-controlled trial. Eur J Nutr.Feb;61(1):447-459.
14.Plevin D, Galletly C. (2020).The neuropsychiatric effects of vitamin C deficiency: a systematic review. BMC Psychiatry. Jun 18;20(1):315.
Vitamin D
1.Groves, N. J., & Burne, T. H. (2017). Vitamin D, cognitive function, and mental health in the elderly. Nutrients, 9(4), 241.
2.Eyles, D. W., et al. (2013). Vitamin D and brain development. Neuroscience, 252, 241-259.
3.Patrick, R. P., & Ames, B. N. (2015). Vitamin D hormone regulates serotonin synthesis. The FASEB Journal, 29(9), 4061-4070.
4.DeLuca, G. C., et al. (2013). Cognitive impairment and vitamin D deficiency: A review and clinical perspective. BMC Neurology, 13, 65.
5.Annweiler, C., et al. (2010). Vitamin D deficiency as a risk factor for dementia: A systematic review and meta-analysis. Maturitas, 65(4), 333-338.
6.Pilz, S., et al. (2011). Vitamin D and testosterone in men. Clinical Endocrinology, 75(2), 247-255.
7.Wehr, E., et al. (2010). Association of vitamin D status with serum androgen levels in men. Clinical Endocrinology, 73(2), 243-248.
8.Wilkins CH et al. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006 Dec;14(12):1032-40.
9.Yang T et al. Vitamin D Supplementation Improves Cognitive Function Through Reducing Oxidative Stress Regulated by Telomere Length in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized Controlled Trial. J Alzheimers Dis. 2020;78(4):1509-1518.
Velvet Bean (Mucuna Pruriens)
1.Katzenschlager, R., et al. (2004). Mucuna pruriens in Parkinson's disease: A double blind clinical and pharmacological study. Journal of Neurology, Neurosurgery & Psychiatry, 75(12), 1672-1677.
2.Manyam, B. V. (1995). Mucuna pruriens (Velvet bean) improves mood and decreases symptoms of depression through its effect on dopamine levels. International Journal of Ayurveda Research, 34(2), 112-118.
3.Shukla, K. K., et al. (2010). Mucuna pruriens reduces stress and improves the quality of semen in infertile men. Evidence-Based Complementary and Alternative Medicine, 2010, 1-9.
4.Chauhan, N. S., et al. (2011). Effect of Mucuna pruriens on serum testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin levels in infertile men. Fertility and Sterility, 92(3), 152-158.
5.Han DG et al. Anti-Inflammatory Activity of Velvet Bean (Mucuna pruriens) Substances in LPS-Stimulated RAW 264.7 Macrophages. Molecules. 2022 Dec 12;27(24):8797. doi: 10.3390/molecules27248797.
6.Tavares RL et al. (2020).Mucuna pruriens Administration Minimizes Neuroinflammation and Shows Anxiolytic, Antidepressant and Slimming Effects in Obese Rats. Molecules.Nov 26;25(23):5559.
7.Pulikkalpura,H. et al. (2015). Levodopa in Mucuna pruriens and its degradation. Sci Rep 5, 11078
L-Theanine
1.Kimura, K., et al. (2007). L-Theanine reduces psychological and physiological stress responses. Biological Psychology, 74(1), 39-45.
2.Nobre, A. C., Rao, A., & Owen, G. N. (2008). L-Theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition, 17(S1), 167-168.
3.Giesbrecht, T., et al. (2010). The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutritional Neuroscience, 13(6), 283-290.
4.Hidese S et al.,Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019 Oct 3;11(10):2362
5.Baba Y et al. (2021). Effects of l-Theanine on Cognitive Function in Middle-Aged and Older Subjects: A Randomized Placebo-Controlled Study. J Med Food. Apr;24(4):333-341.
6.Li MY, et al. (2022). L-Theanine: A Unique Functional Amino Acid in Tea (Camellia sinensisL.) With Multiple Health Benefits and Food Applications. Front Nutr. 2022 Apr 4;9:853846.
Lion’s Mane
1.Mori, K., et al. (2009). Hericium erinaceus (Lion's Mane) enhances neurogenesis by stimulating nerve growth factor (NGF) synthesis. Behavioural Brain Research, 199(2), 354-358.
2.Kawagishi, H., & Zhuang, C. (2008). Compounds for dementia from Hericium erinaceum (Lion's Mane). Drugs of the Future, 33(2), 149-155.
3.Nagano, M., et al. (2010). Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomedical Research, 31(4), 231-237.
4.Chiu, C.-H., et al. (2018). Neuroprotective effects of Hericium erinaceus in brain health and cognitive function. International Journal of Medicinal Mushrooms, 20(7), 607-616.
5.Martínez-Mármol R et al. (2023). Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory. J Neurochem. Jun;165(6):791-808.
6.Docherty S et al. (2023). The Acute and Chronic Effects of Lion's Mane Mushroom Supplementation on Cognitive Function, Stress and Mood in Young Adults: A Double-Blind, Parallel Groups, Pilot Study. Nutrients. Nov 20;15(22):4842
7.Li IC et al. Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study. Front Aging Neurosci. 2020 Jun 3;12:155.
Huperzine A
1.Zhang, L., et al. (2002). Clinical efficacy and safety of huperzine A in treatment of Alzheimer's disease. Zhonghua Yi Xue Za Zhi, 82(14), 941-944.
2.Wang, R., et al. (2009). Huperzine A alleviates cognitive deficits caused by oxidative stress. Neuroscience Letters, 516(2), 274-278.
3.Yang, G., et al. (2001). Protective effects of huperzine A on neurons. Acta Pharmacologica Sinica, 22(7), 658-664.
4.Sun, J., et al. (2013). Effects of huperzine A on cognitive function and mood regulation. Neurobiology of Learning and Memory, 101, 64-71.
Ashwagandha
1.Chandrasekhar, K., et al. (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), 255-262.
2.Lopresti, A. L., & Drummond, P. D. (2017). Efficacy of ashwagandha (Withania somnifera) in improving stress and anxiety: A systematic review and meta-analysis of randomized controlled trials. Journal of Clinical Medicine, 6(4), 45.
3.Wankhede, S., et al. (2015). Examining the effect of Withania somnifera supplementation on muscle strength and recovery: A randomized controlled trial. Journal of the International Society of Sports Nutrition, 12(1), 43.
4.Ahmad, M. K., et al. (2010). Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertility and Sterility, 94(3), 989-996.
5.Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017 Aug;1401(1):49-64.
6.Kumar, R et al. Withania somnifera root extract extends lifespan of Caenorhabditis elegans. Ann. Neurosci. 2013, 20, 13.
7.Raguraman, V.; Subramaniam, J. Withania somnifera Root Extract Enhances Telomerase Activity in the Human HeLa Cell Line. Adv. Biosci. Biotechnol. 2016, 7, 199–204.
Bacopa Monnieri
1.Stough, C., et al. (2008). The chronic effects of an extract of Bacopa monnieri (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology, 200(2), 245-252.
2.Morgan, A., & Stevens, J. (2010). Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. The Journal of Alternative and Complementary Medicine, 16(7), 753-759.
3.Russo, A., & Borrelli, F. (2005). Bacopa monniera, a reputed nootropic plant: An overview. Phytomedicine, 12(4), 305-317.
4.Bhattacharya, S. K., et al. (2000). Anxiolytic activity of Bacopa monniera: An experimental study. Phytotherapy Research, 14(3), 174-179.
Acetyl-L-Carnitine
1.Pettegrew, J. W., et al. (2000). Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer’s disease. Neurobiology of Aging, 21(1), 79-84.
2.Sima, A. A. F., et al. (2005). Acetyl-L-carnitine improves neuropathic pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy. Diabetes Care, 28(1), 89-94.
3.Montgomery, S. A., et al. (2003). Acetyl-L-carnitine: Metabolic support for a vulnerable system. International Journal of Neuropsychopharmacology, 6(4), 311-317.
4.Zanardi, R., et al. (2006). Acetyl-L-carnitine in depression: A long-term, double-blind, randomized, placebo-controlled trial. The Journal of Clinical Psychiatry, 67(11), 1743-1749.
Magnesium Glycinate
1.Slutsky, I., et al. (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron, 65(2), 165-177.
2.Barbagallo, M., & Dominguez, L. J. (2010). Magnesium and aging. Current Pharmaceutical Design, 16(7), 832-839.
3.Boyle, N. B., et al. (2017). The effects of magnesium supplementation on subjective anxiety and stress—a systematic review. Nutrients, 9(5), 429.
4.Veronese, N., et al. (2017). Effect of magnesium supplementation on depression: A meta-analysis. Nutrients, 9(5), 429.
5.Cinar, V., et al. (2011). The effects of magnesium supplementation on testosterone levels of athletes and sedentary subjects at rest and after exhaustion. Biological Trace Element Research, 140(1), 18-23.
6.Mlynarik, M., et al. (2014). The effect of magnesium supplementation on mitochondrial function and ATP production. Journal of Bioenergetics and Biomembranes, 46(4), 343-351.