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What natural foods boost neurotransmitters that could therapeutically affect neurological and/or neurodegenerative diseases?

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Stephanie Holst Sep 22, 2020
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From the known excitatory or inhibitory responses elicited by neurotransmitters (NTs), what natural foods/supplements can be used to improve neurological disorders such as depression or ADHD, or improve memory and/or function in neurodegenerative diseases such as Alzheimer’s, Parkinson’s or Huntington’s?

The electrical signal of a neuron crosses a synapse to signal another neuron via chemical messengers, or NTs. There are anywhere from 50 to 100 various NTs that have been identified in the human body, of these only a few have been well studied and their neurological roles understood.

Dopamine, an excitatory NT, regulates pleasure, helps with control of movement, cognition, and motivation. High levels of dopamine help to increase mood and movement, too much dopamine can cause aggressiveness and irritability, as seen in Schizophrenia, or too little can lead to Parkinson’s motor symptoms.

Caffeine causes a more complex NT response than other stimulants that directly boost dopamine, in that it produces motor activation by blocking adenosine A2A receptor–mediated inhibition of dopamine D2 receptor activation. It has also been shown to protect against dopaminergic neuronal loss, increase glutamate concentrations, modulate glutamatergic receptors and transporters, and affect the GABAergic system.

Is caffeine from varied sources such as matcha, coffee, green tea, etc. more or less effective? What other foods/supplements boost NTs involved in memory, movement, or learning?

[1]1. Center for Substance Abuse Treatment. Treatment for Stimulant Use Disorders. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 1999. (Treatment Improvement Protocol (TIP) Series, No. 33.) Chapter 2—How Stimulants Affect the Brain and Behavior. Available from: https://www.ncbi.nlm.nih.gov/books/NBK64328/

[2]Planning Committee for a Workshop on Potential Health Hazards Associated with Consumption of Caffeine in Food and Dietary Supplements; Food and Nutrition Board; Board on Health Sciences Policy; Institute of Medicine. Caffeine in Food and Dietary Supplements: Examining Safety: Workshop Summary. Washington (DC): National Academies Press (US); 2014 Apr 23. 6, Caffeine Effects on the Central Nervous System and Behavioral Effects Associated with Caffeine Consumption. Available from: https://www.ncbi.nlm.nih.gov/books/NBK202225/

[3]Alasmari F. Caffeine induces neurobehavioral effects through modulating neurotransmitters. Saudi Pharm J. 2020;28(4):445-451. doi:10.1016/j.jsps.2020.02.005

Creative contributions

Can the Mediterranean help?

Juran Sep 22, 2020
Although it may seem too obvious or too simple, it's proven that the Mediterranean diet reduces all-cause mortality, improves general health, and help retain the cognitive functions in old age [1,2,3]. Are the answers to increased brain healthspan hidden in Greek villages? Inspired by the food consumed in villages of Croatia, Spain, Italy, Cyprus, Morocco, Portugal, and Greece, the Mediterranean diet is nowadays widely accepted diet based on vegetable, fruit, whole grains, seeds, nuts, beans, oils, fish, and red wine [1,4]. In 2017, researchers again confirmed this specific diet can have a positive effect on our mental health, but they also stated that fish and meat consumption were not related to brain changes, like thought before [5]. Therefore, some other segments of the diet could be responsible for the beneficial effect or it could be a combination of many. That it can help battling specific disorders, supports the research which estimated that there could be a 3.5-year delay in the progression of Alzheimer's in people who ate the Mediterranean, instead of Western food [6,7]. Another study showed that people who consumed extra virgin oil or increased fruit intake had a lower risk of depression. Seeds and oats help you retain serotonin levels as an L-tryptophan source [8]. If you still need proof to start eating healthy or researching it, the fact is that the Mediterranean diet is considered to be so specific and beneficial that, in 2013, it was included on the "intangible cultural heritage of humanity" list [4]! Do you know any neurotransmitter hidden in the food mentioned above? [1] https://www.mercy.net/service/neurology-services/eating-for-your-brain-two-diets-that-can-enhance-neurological-health/ [2] https://academic.oup.com/nutritionreviews/article/76/3/204/4810491 [3] https://www.ahajournals.org/doi/10.1161/CIR.0000000000000678 [4] https://ich.unesco.org/en/RL/mediterranean-diet-00884 [5] https://www.aan.com/PressRoom/Home/PressRelease/1511 [6] https://www.nih.gov/news-events/nih-research-matters/mediterranean-diet-may-slow-development-alzheimers-disease [7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673956/ [8] https://www.mediterraneanliving.com/alleviating-depression-with-mediterranean-diet/
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The ketogenic diet

Shubhankar Kulkarni
Shubhankar Kulkarni Sep 24, 2020
The ketogenic diet is used to treat pharmacoresistant epilepsy. [1] Researchers demonstrated that in a mouse model of amyotrophic lateral sclerosis, the administration of a ketogenic diet led to a higher motor neuron survival and an improvement in motor function compared to control mice. [2] Moreover, the ketogenic diet mimics fasting or caloric restriction. It activates AMPK and SIRT-1 signaling, thereby decreasing mTOR signaling. [3] This produces beneficial effects on glucose homeostasis and insulin action [4] and also anti-aging effects. Since Alzheimer’s disease is associated with metabolic dysregulation, insulin resistance, [5] and aging, several researchers have demonstrated that a ketogenic diet significantly improves glucose homeostasis by reducing metabolic dysregulation and insulin resistance. [6-8] An in vitro study demonstrated that beta-hydroxybutyrate (a ketone body) protects the hippocampal neurons from amyloid-β toxicity (amyloid-β toxicity is implicated in Alzheimer’s disease). [9] Infusion of β-hydroxybutyric acid protected the mice from dopaminergic neurodegeneration and motor deficits. [10] In a rat model of Parkinson’s disease, the ketogenic diet protected dopaminergic neurons of the substantia nigra against 6-hydroxydopamine neurotoxicity. [11] In humans, a “hyperketogenic” diet for 28 days improved the Unified Parkinson's Disease Rating Scale scores. [12] References: 1. Paoli A, Bianco A, Damiani E, Bosco G. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases. Biomed Res Int [Internet]. 2014;2014:1–10. Available from: http://www.hindawi.com/journals/bmri/2014/474296/ 2. Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, et al. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci [Internet]. 2006 Apr 3;7:29. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16584562 3. Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab [Internet]. 2014 Jan;25(1):42–52. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1043276013001562 4. Ruderman NB, Julia Xu X, Nelson L, Cacicedo JM, Saha AK, Lan F, et al. AMPK and SIRT1: a long-standing partnership? Am J Physiol Metab [Internet]. 2010 Apr;298(4):E751–60. Available from: https://www.physiology.org/doi/10.1152/ajpendo.00745.2009 5. Akter K, Lanza EA, Martin SA, Myronyuk N, Rua M, Raffa RB. Diabetes mellitus and Alzheimer’s disease: shared pathology and treatment? Br J Clin Pharmacol [Internet]. 2011 Mar;71(3):365–76. Available from: http://doi.wiley.com/10.1111/j.1365-2125.2010.03830.x 6. Westman EC, Yancy WS, Mavropoulos JC, Marquart M, McDuffie JR. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond) [Internet]. 2008 Dec 19;5(1):36. Available from: https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-5-36 7. Paoli A, Bianco A, Grimaldi K, Lodi A, Bosco G. Long Term Successful Weight Loss with a Combination Biphasic Ketogenic Mediterranean Diet and Mediterranean Diet Maintenance Protocol. Nutrients [Internet]. 2013 Dec 18;5(12):5205–17. Available from: http://www.mdpi.com/2072-6643/5/12/5205 8. Dashti HM, Mathew TC, Khadada M, Al-Mousawi M, Talib H, Asfar SK, et al. Beneficial effects of ketogenic diet in obese diabetic subjects. Mol Cell Biochem [Internet]. 2007 Jul 23;302(1–2):249–56. Available from: http://link.springer.com/10.1007/s11010-007-9448-z 9. Kashiwaya Y, Bergman C, Lee J-H, Wan R, King MT, Mughal MR, et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol Aging [Internet]. 2013 Jun;34(6):1530–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0197458012006112 10. Tieu K, Perier C, Caspersen C, Teismann P, Wu D-C, Yan S-D, et al. D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J Clin Invest [Internet]. 2003 Sep 15;112(6):892–901. Available from: http://www.jci.org/articles/view/18797 11. Cheng B, Yang X, An L, Gao B, Liu X, Liu S. Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson’s disease. Brain Res [Internet]. 2009 Aug;1286:25–31. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0006899309012797 12. VanItallie TB, Nonas C, Di Rocco A, Boyar K, Hyams K, Heymsfield SB. Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study. Neurology [Internet]. 2005 Feb 22;64(4):728–30. Available from: http://www.neurology.org/cgi/doi/10.1212/01.WNL.0000152046.11390.45
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Tea, Cocoa, Ginseng, Galangal, Squash, Gingko

Shubhankar Kulkarni
Shubhankar Kulkarni Sep 25, 2020
1. Tea (Camellia sinensis) - reduced risk of stroke and depression [1] 2. Cocoa (Theobroma cacao) - promotes neurogenesis, improve neuronal function, and increases blood flow to the brain and sensory systems. [2] It has been used to enhanced cognition. [3] Consumption has been shown to prevent depression since cocoa-derived tryptophan is converted to serotonin. [4] 3. Ginseng (Panax ginseng) - Ginseng extract was successfully used as a cognitive enhancer to treat Alzheimer's disease. [5] Active components of ginseng prevented amyloid β formation and spatial memory impairment in rats. [6] It also inhibited the formation of advanced glycation end products (AGE). [7] It blocked the generation of reactive oxygen species (ROS) and, therefore, neuronal apoptosis. [8] 4. Galangal (Alpinia galangal) – A central nervous system stimulant that increased motor coordination in mice. [9] 5. Squash (Cucurbita maxima) - oil obtained from the seeds is used to treat nervous disorders and depression. [10] 6. Ginkgo (Ginkgo biloba) - used in the treatment of vertigo, short term memory loss, and lack of attention. Extract of ginkgo acted as a cognitive enhancer in human subjects experiencing dementia. [11] Ginkgo has radical scavenger activity and it acts as a neuroprotective that inhibits amyloid-β neurotoxicity. [12,13] References: 1. Bhatti SK, O’Keefe JH, Lavie CJ. Coffee and tea. Curr Opin Clin Nutr Metab Care [Internet]. 2013 Nov;16(6):688–97. Available from: http://journals.lww.com/00075197-201311000-00014 2. Sokolov AN, Pavlova MA, Klosterhalfen S, Enck P. Chocolate and the brain: Neurobiological impact of cocoa flavanols on cognition and behavior. Neurosci Biobehav Rev [Internet]. 2013 Dec;37(10):2445–53. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0149763413001681 3. Latif R. Health benefits of cocoa. Curr Opin Clin Nutr Metab Care [Internet]. 2013 Nov;16(6):669–74. Available from: http://journals.lww.com/00075197-201311000-00011 4. Araujo QR De, Gattward JN, Almoosawi S, Parada Costa Silva M das GC, Dantas PADS, Araujo Júnior QR De. Cocoa and Human Health: From Head to Foot—A Review. Crit Rev Food Sci Nutr [Internet]. 2016 Jan 2;56(1):1–12. Available from: http://www.tandfonline.com/doi/full/10.1080/10408398.2012.657921 5. Song X-Y, Hu J-F, Chu S-F, Zhang Z, Xu S, Yuan Y-H, et al. Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats. Eur J Pharmacol [Internet]. 2013 Jun;710(1–3):29–38. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0014299913002884 6. Woelk H, Arnoldt KH, Kieser M, Hoerr R. Ginkgo biloba special extract EGb 761® in generalized anxiety disorder and adjustment disorder with anxious mood: A randomized, double-blind, placebo-controlled trial. J Psychiatr Res [Internet]. 2007 Sep;41(6):472–80. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022395606001026 7. Quan HY, Kim DY, Chung SH. Korean red ginseng extract alleviates advanced glycation end product-mediated renal injury. J Ginseng Res [Internet]. 2013 Apr 15;37(2):187–93. Available from: http://koreascience.or.kr/journal/view.jsp?kj=GROSBR&py=2013&vnc=v37n2&sp=187 8. Kim S, Lee Y, Cho J. Korean Red Ginseng Extract Exhibits Neuroprotective Effects through Inhibition of Apoptotic Cell Death. Biol Pharm Bull [Internet]. 2014;37(6):938–46. Available from: http://jlc.jst.go.jp/DN/JST.JSTAGE/bpb/b13-00880?lang=en&from=CrossRef&type=abstract 9. Saha S, Banerjee S. Central nervous system stimulant actions of Alpinia galanga (L.) rhizome: a preliminary study. Indian J Exp Biol [Internet]. 2013 Oct;51(10):828–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24266107 10. Muntean, E., Muntean, N., & Duda, M. (2014). Cucurbita maxima Duch. as a medicinal plant. Hop and Medicinal Plants, 21, 75-80. 11. Williams B, Watanabe CM., Schultz PG, Rimbach G, Krucker T. Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability. Neurobiol Aging [Internet]. 2004 Aug;25(7):955–62. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0197458003002379 12. KAMPKOTTER A, PIELARSKI T, ROHRIG R, TIMPEL C, CHOVOLOU Y, WATJEN W, et al. The Ginkgo biloba extract EGb761 reduces stress sensitivity, ROS accumulation and expression of catalase and glutathione S-transferase 4 in Caenorhabditis elegans. Pharmacol Res [Internet]. 2007 Feb;55(2):139–47. Available from: https://linkinghub.elsevier.com/retrieve/pii/S104366180600209X 13. Tan X, Gu J, Zhao B, Wang S, Yuan J, Wang C, et al. Ginseng improves cognitive deficit via the RAGE/NF-κB pathway in advanced glycation end product-induced rats. J Ginseng Res [Internet]. 2015 Apr;39(2):116–24. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1226845314001043
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Velvet beans

Povilas S
Povilas S Oct 04, 2020
Beans of Mucuna pruriens plant species have high concentrations (~4% in raw beans) [1] of L-DOPA, a precursor to dopamine. Increasing L-DOPA concentrations in the organism through diet can help produce more dopamine, therefore could be used in treating Parkinson's disease and other dopamine deficiency-related disorders. Double-blind experiment with people having Parkinson's disease proved velvet beans to be more effective than standardized L-DOPA supplement. It can also be beneficial for healthy people to naturally boost mood and motivation.

The beans are valuable source of food, however, high concentrations of L-DOPA present in the beans may cause unwanted side effects such as nausea, arrhythmias, and hypotension. They also contain trypsin inhibitors [2], that reduce protein absorption, therefore it's better to cook them before - heat eliminates or at least reduces trypsin inhibitors and reduces L-DOPA content [1], this way a person can still get some L-DOPA with a lower probability to experience side effects. Therefore incorporating cooked beans into general diet might be a good way to naturally increase your dopamine levels. It was also showed that germination of the beans reduced trypsin inhibitor activity by 82 percent.[2] Maybe combining cooking with germination could be the best preparation method.

The plant is not an easy one to handle though, it's notorious for producing extreme itchiness upon contact with the skin. Husked beans don't produce the itchiness, but the stinging hairs covering seed pods and other parts of the plant.
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Chamomile decreases anxiety

Shubhankar Kulkarni
Shubhankar Kulkarni Oct 02, 2020
A randomized, double-blind, placebo-controlled study in humans suggests that Chamomile (Matricaria recutita) may have anxiolytic and antidepressant activity. The tolerability of chamomile extract therapy in patients with mild to moderate generalized anxiety disorder (GAD) was assessed. After 8 weeks of therapy, a significant reduction in the anxiety score was observed. Chamomile tea is widely used in many countries and chamomile is also a part of herbal tea preparations.

[1]Amsterdam JD, Li Y, Soeller I, Rockwell K, Mao JJ, Shults J. A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder. J Clin Psychopharmacol. 2009 Aug;29(4):378-82. doi: 10.1097/JCP.0b013e3181ac935c. PMID: 19593179; PMCID: PMC3600416.

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Choline supplementation

Jamila Sep 24, 2020
Choline is the precursor to acetylcholine, a neurotransmitter that regulates nervous system functions such as muscle control, mood, memory, and other cognitive abilities. Interestingly, it has been reported that individuals with Alzheimer’s disease have decreased levels of acetylcholine. Acetylcholine stimulates the Alpha7 nicotinic acetylcholine receptor on microglia. In Alzheimer's disease, microglia are constantly stimulated. It is thought that this constant stimulation drives chronic inflammation and cell death in the disease. Alpha7 nicotinic acetylcholine receptor and Sigma‐1 R (σ1R) modulate the central nervous system. So, Alzheimer’s disease progresses when these receptors become dysfunctional. In one recent study, researchers fed mice a diet supplemented with choline (5.0 g/kg). It was found that the long term use of the choline supplement was able to dramatically improve spatial memory in the mice and decrease the build-up of amyloid-beta plaque. Furthermore, decreases in microglial stimulation and specific receptors (alpha7 nicotinic acetylcholine receptor and Sigma‐1 R) was observed. Therefore, a diet supplemented with choline may be able to attenuate Alzheimer's disease pathophysiology. In the United States, the acceptable amount of choline intake is 550 mg a day for men and 425 mg a day for women. However, researchers suggest this may not be enough. High levels of choline can be found in many different foods including: • Eggs • Chicken liver • Milk • Beef • Cod • and much more Alternatively, there are choline supplements that are widely available in-store and online. Choline can come in the forms of lecithin, phosphatidylcholine, and choline bitartrate. Choline supplements contain in the region of 10 mg – 250 mg of choline (although there are some exceeding those values).

[1]Zeisel, Steven H. "Choline: essential for brain development and function." Advances in pediatrics 44 (1997): 263-295.

[2]Francis, Paul T. "The interplay of neurotransmitters in Alzheimer's disease." CNS spectrums 10.S18 (2005): 6-9.

[3]Pohanka, Miroslav. "Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and toxicology." International journal of molecular sciences 13.2 (2012): 2219-2238.

[4]Schwab, Claudia, Andis Klegeris, and Patrick L. McGeer. "Inflammation in transgenic mouse models of neurodegenerative disorders." Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1802.10 (2010): 889-902.

[5]Velazquez, Ramon, et al. "Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation." Aging Cell 18.6 (2019): e13037.

[6]“Office of Dietary Supplements - Choline.” NIH Office of Dietary Supplements, U.S. Department of Health and Human Services, 10 July 2020, ods.od.nih.gov/factsheets/Choline-HealthProfessional/.

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Danshen water extract for Alzheimer's disease

Jamila Oct 05, 2020
As we already know, Alzheimer's disease is characterised with the build-up of amyloid-beta plaque. In a study, Yuen and colleagues determined the effect of using the Danshen water extract in a C. elegans Alzheimer's model. The Danshen water extract is a Chinese herbal remedy; the extract itself comes from the rhizome and dried root of Salvia miltiorrhiza. The researchers found that the components of the Danshen water extract were able to bind onto amyloid-beta and impede plaque aggregation. Furthermore, the researchers suggest that the extract was able to decrease paralysis in the disease model because of its antioxidant properties.

[1]Yuen, Chee Wah, et al. "Danshen (Salvia miltiorrhiza) water extract shows potential neuroprotective effects in Caenorhabditis elegans." Journal of Ethnopharmacology (2020): 113418.

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Fermented foods improve mood

Shubhankar Kulkarni
Shubhankar Kulkarni Oct 20, 2020
Fermented foods like yogurt may improve gut health and overall mood. Fermentation allows live bacteria to thrive (probiotics). These live microbes support the growth of healthy bacteria in the gut and may increase serotonin levels. Serotonin (a neurotransmitter) improves mood and stress response. Up to 90% of the body’s serotonin is produced by the gut microbiome. The gut microbiome also plays a role in brain health. There is evidence of a correlation between healthy gut bacteria and lower rates of depression.

However, not all fermented foods are significant sources of probiotics. Bread, beer, and wine are cooked or filtered and, hence, lose the microbial population.

[1]Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015 Apr 9;161(2):264-76. doi: 10.1016/j.cell.2015.02.047. Erratum in: Cell. 2015 Sep 24;163:258. PMID: 25860609; PMCID: PMC4393509.

[2]O'Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res. 2015 Jan 15;277:32-48. doi: 10.1016/j.bbr.2014.07.027. Epub 2014 Jul 29. PMID: 25078296.

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