Week 15: Phytonutrients/
Antioxidants and Brain Health
Recording:
Miss the class? View the recording by Dr. Minoo as she explains the lesson on phytonutrients and polyphenols.
Suggested class for summer:
Try a different class with your Brain Fitness this summer. Brain Fitness instructor Mindy Sloan will be offering a five week session on Creativity, Spirituality and Self-expression. View the flyer here.
Sloan Psyc summer24.pdfPhytonutrients/Antioxidants and Brain Health
There are thousands of phytonutrients found in plant foods. This class will summarize the effects of phytonutrients, such as anthocyanins and curcumin, on cognitive function. Phytonutrients also have antioxidant and anti-inflammatory properties that may help support a healthy brain.
Video:
In this video, we learn about phytonutrients and a way to better identify them (by color). Nice introduction to the lesson.
Let’s Review: What does inflammation mean?
If you’ve ever cut your finger, bruised a toe or had a throat infection, you have likely experienced at least some of the four signs of inflammation: redness, swelling, pain and heat. Acute inflammation is your body’s natural response to illness, injury or infection and usually resolves on its own.
Systemic inflammation is another kind of inflammation that affects the whole body. Systemic inflammation can become chronic, meaning it can last for months, or even years.
Systemic inflammation may be a factor in:
○ Obesity
○ metabolic syndrome
○ prediabetes
○ type 2 diabetes
○ heart disease
○ IBS
○ some forms of cancer
○ arthritis
○ Alzheimer’s disease
○ Cognitive decline
Oxidative stress and inflammation
Oxidative stress is viewed as an imbalance between the production of reactive oxygen species (ROS) and their elimination by protective mechanisms (such as our antioxidant system). The excessive production of ROS may cause tissue injury that may lead to the inflammatory process and chronic inflammation. The inflammation triggered by oxidative stress may be the cause of many chronic conditions such as type 2 diabetes and cardiovascular disease. Imbalance in this protective mechanism can lead to the damage of cellular molecules such as DNA, proteins, and lipids.
Oxidative stress can activate a variety of transcription factors, which lead to the differential expression of some genes involved in inflammatory pathways. The inflammation triggered by oxidative stress is the cause of many chronic diseases. During cognitive decline, we produce excessive amounts of free radicals leading to cell damage associated with neurodegeneration (damage to brain cells and neurons).
Antioxidants, including vitamins like C and E, as well as some phytonutrients, serve to neutralize the oxidative species and protect our DNA and cells from damage. It’s thought that many polyphenols exert their effect on cognitive function by improving neuron generation and survival by reducing oxidative stress and damage.
https://warnerorthopedics.com/how-oxidative-stress-directly-contributes-to-low-grade-inflammation/
What are phytonutrients and polyphenols?
Phytonutrients, also known as phytochemicals, are naturally occurring chemical compounds found in plant-based foods that often contribute to the color of fruits, vegetables, herbs, teas, legumes, nuts/seeds and grains. Just like macronutrients (carbs, protein, fat), and micronutrients (vitamins and minerals), phytonutrients have a wide range of benefits to our health.
There are thousands of phytonutrients, and we’re only beginning to scratch the surface of our understanding of them. However, the preliminary science is promising. The benefits associated with these compounds include antioxidant, anti-inflammatory, antiviral, and antibacterial effects, repairing cell damage, and immune function.
https://fullscript.com/blog/polyphenols
Polyphenols represent a large category of phytonutrients that are powerful antioxidants with free radical scavenging capabilities as well as anti-inflammatory activity. They have been shown, in general, to reduce oxidative stress and the risk for many diseases, including neurodegenerative diseases such as Alzheimer’s disease, as well as Parkinson’s disease. The consumption of certain polyphenols (e.g., flavonoids) has been shown to enhance learning and memory as well as general improvement of cognition.
Antioxidant properties of polyphenols
Polyphenols are reducing agents, and together with other dietary reducing agents, such as vitamin C, vitamin E and carotenoids (referred to as antioxidants), protect the body's tissues against oxidative stress and associated conditions such as cancers, coronary heart disease and inflammation.
Polyphenol antioxidant activities are related to their capacity to scavenge and neutralize a wide range of reactive oxygen species (ROS). Because of their anti-inflammatory effect associated with antioxidant activity, polyphenols have been proposed to be useful as adjuvant therapy (to lower the risk of cancer coming back).
Polyphenols are the most abundant antioxidants. Fruits, vegetables, grains, spices and herbs are the richest source of dietary polyphenols. High intake of these foods has been linked to lowered risk of most common degenerative and chronic diseases that are known to be caused by oxidative stress.
More than 8,000 types of polyphenols have been identified. This lesson will focus on specific polyphenols from the following groups:
● Flavonoids. ~60% of all polyphenols; quercetin, kaempferol, catechins, and anthocyanins, which are found in foods like apples, onions, dark chocolate, coffee, tea and purple fruits/vegetables; isoflavones in soy
● Oleuropein, Hydroxytyrosol, Tyrosol polyphenols in Olives
● Stilbenoid polyphenol; resveratrol in grapes and berries
● Diterpene polyphenol; carnosic acid in herbs
● Phenolic acids ~30% of all polyphenols; curcumin in turmeric
Different categories of polyphenols and their effects on brain function
Flavonoids
Flavonoids such as quercetin, kaempferol, and myricetin are the most abundant flavonoids in plant foods. A recent study (Jan 2020) of older adults infers that people who consumed the highest dietary intake of flavonols were 48% less likely to develop Alzheimer’s dementia (AD) than people with the lowest intake of these foods.
The flavonoid quercetin may possess a protective effect against the neurotoxicity of amyloid β-peptide associated with AD. Quercetin has also been found to modulate biological inflammatory pathways, which could lead to an improvement in inflammation involved in neurodegenerative diseases. Foods high in quercetin include: citrus fruits, apples, onions, parsley, sage, tea, and red wine, olive oil, grapes, dark cherries, and dark berries such as blueberries, blackberries.
In general, foods high in flavonoids include:
● Apples
● Berries
● Broccoli
● leafy vegetables
● Onions
● Scallions
● Teas
● Herbs
● Wine
Special notes on Blueberries
Blueberries have been shown to be beneficial for cognitive performance. A high quality study showed enhanced neural response during working memory challenges in older adults with mild cognitive impairment. Blueberry concentrate (supplementation) improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.
Anthocyanins
Anthocyanins are flavonoid pigments that give plants deep red, purple and blue colors. They are powerful phytonutrients that protect our heart and brain health. They also have antitumor properties.
Foods high in anthocyanins include:
● Deep red, purple berries and blueberries
● Cherries
● Red wine
● Leafy and root vegetables (eggplant, cabbage, beans, onions, radishes)
https://www.researchgate.net/publication/358638903_Biosynthesis_and_regulation_of_anthocyanin_pathway_genes/figures?lo=1
Isoflavones in soy and soy-derived foods
Isoflavones, one of the better absorbed flavonoids, are specific to soy and soy-based foods, such as soybeans, tofu, soy milk and tempeh.
Many current neuroprotective studies on isoflavones focus on postmenopausal women. Postmenopausal women have lower endogenous estrogen levels and tend to be at a higher risk of Alzheimer’s Disease. Long-term low levels of estrogen that occur in menopausal women can reduce the number of estrogen receptors in the brain that are necessary for specific cognitive functions like memory and learning. The soy isoflavone, daidzein, has been hypothesized to reduce decline in cognitive function or disease processes related to cognition and behavior. Therefore, eating soy foods may help prevent age-related memory loss or decline in thinking skills. [Ahmed et al., 2017].
A series of high quality studies (randomized controlled trials) investigated the effects of soy isoflavones, particularly the estrogen-like actions, on cognition-related aspects. In these studies, doses of total isoflavones varied between 60 and 110 mg/day; and intervention ranged from 12 weeks to 2.5 years. Many studies revealed promising results in specific aspects of cognitive function, such as information integration, incidental learning, category fluency, frontal lobe function, and recall of pictures and sustained attention tasks. However, almost half of the studies failed to support a significant role of isoflavones supplementation in improving cognitive function. (Yang et al, 2021).
Aside from their isoflavone content, soy foods are rich in nutrients including B vitamins, fiber, potassium, magnesium, and high-quality protein. Soy protein is considered a complete protein, containing all nine essential amino acids that the body cannot make which must be obtained from the diet. Soy foods are also classified as fermented or unfermented. Fermented means that the soy food has been cultured with beneficial bacteria, yeast, or mold (e.g., Miso and Tempeh). Fermenting soy may improve its digestibility and absorption in the body, as this process partially breaks down soy’s sugar and protein molecules.
Fermented soy foods commonly eaten in East Asian diets, including natto, tempeh and miso contain isoflavones and also bacteria that might have benefits for neurological disorders including cognitive decline, Alzheimer’s disease (AD), and Parkinson’s disease (PD). Soy’s antioxidant and anti-inflammatory effects may reduce the oxidative stresses associated with AD and PD [Jang et al., 2021]. Furthermore, fermented soy foods are produced with beneficial bacteria like Lactobacilli, Bifidobacteria, and Bacillus species that produce butyrate, a short-chain fatty acid that regulates immune function and is being investigated for its protective effects on the brain.
https://www.iasoybeans.com/newsroom/article/celebrating-soyfoods-month-were-eating-more-soy
https://fanaticcook.com/2016/09/23/plant-based-diets-may-offer-protection-against-diabetes/
Catechins/Epicatechins
Catechins and epicatechins belong to the flavonoid group of polyphenols. Research investigating the relations between cocoa and cognition show improvements in general cognition, attention, processing speed, and working memory. Cocoa flavonoids could also enhance normal cognitive functioning and exert a protective role on cognitive performance. Look for dark chocolate (recommend 70% or more). This is the form that has been shown to increase a person’s total antioxidant capacity and reduce the risk of cognitive decline.
Catechins and epicatechins are found in:
● Cocoa/chocolate
● Green tea
● red wine
● broad beans (fava beans)
● black grapes
● Apricots
● Strawberries, Raspberries, Blackberries
● Apples
● Cherries
● Pears
Epigallocatechin gallate (EGCG)
The flavonoid Epigallocatechin gallate (EGCG), can be found in high amounts in green and white tea. Green tea has been shown to improve working memory – the capacity to hold information briefly in memory while performing other mental operations on the information. Both green and white tea extracts have been shown to inhibit an enzyme called acetylcholinesterase, a mechanism that may be a potential treatment of AD and dementia.
https://www.mdpi.com/2072-6643/15/13/3022
Pair these foods with Olive oil for best benefits (https://medium.com/@freshharvestco/5-benefits-of-using-high-polyphenol-organic-extra-virgin-olive-oil-b0911c974a91)
Oleuropein, Hydroxytyrosol, Tyrosol - Olive polyphenols
Olive oil contains over 30 phenolic compounds that are potent antioxidants and free radical scavengers, and the major phenolic compounds in olive oil are oleuropein, hydroxytyrosol and tyrosol.
In addition to the antioxidant activity of these polyphenols, there is a great potential for these compounds to counteract amyloid aggregation and toxicity on the pathways involved in the onset and progression of Alzheimer’s disease.
Recommendation: cold-pressed, extra virgin olive oil, in a dark glass bottle. Keep it out of direct sunlight and use it before the best by date.
Resveratrol
Resveratrol, a stilbenoid polyphenol, has been known to possess cardiovascular benefits but has also been found to enhance brain health. Benefits involve multiple mechanisms including anti-oxidative and anti-inflammatory. Because of its effects on vascular function, resveratrol increases cerebral blood flow and improves synaptic neuroplasticity (building new neuronal connections).
Regular consumption of foods rich in resveratrol has been shown to enhance brain function, memory, and brain connectivity in older adults. Resveratrol is found in the greatest amounts in grapes and red wine. NOTE: Consumption of alcohol might have a negative effect on brain health, not outweighed by the relatively small resveratrol concentration.
Resveratrol may also be consumed in:
● Grapes
● Peanuts
● Blueberries
● Raspberries
● Mulberries
https://www.underherb.com/info/what-foods-have-resveratrol-51901669.html
Carnosic Acid
Carnosic acid is a diterpene polyphenol and found in herbs such as rosemary, sage and oregano. Carnosic acid possesses antioxidant and antimicrobial properties. Additionally, carnosic acid’s anti apoptotic (prevention of cell death) could play a protective role in the prevention of neurodegeneration.
The benefits of carnosic acid may be consumed as whole herbs or extracts, as well as essential oils. One very small, yet interesting study found that inhaling rosemary oil helps prevent the breakdown of acetylcholine, a brain chemical that plays an important role in concentration and memory.
Curcumin
Curcumin, belonging to the group of phenolic acids, is the source of the spice turmeric and is used in dishes from India, Asia and the Middle East. Historically, turmeric was used in Ayurveda and other traditional Indian medical systems, as well as Eastern Asian medical systems such as traditional Chinese medicine. In India, it was traditionally used for disorders of the skin, upper respiratory tract, joints, digestive system, and as a pain relieving, anti-inflammatory agent to relieve pain and inflammation in the muscles. It has also proven to have anti-cancer properties. Curcumin holds a high place in Ayurvedic medicine as a “cleanser of the body,” and today, science is finding a growing list of chronic conditions that can be managed or healed by the active ingredients of turmeric, including joint inflammation (osteoarthritis).
Curcumin has been associated with general improvements in cognitive function and protective effects against various brain diseases. Specifically, curcumin has potent antioxidant and anti-inflammatory properties and may protect the brain from oxidative stress which may reduce the risk of cognitive decline. One observational study in older Asian adults found that curcumin consumption was associated with improvements in the maintenance of attention, short-term working memory, language, and executive function over time.
Unfortunately, the curcumin in turmeric is poorly absorbed into the bloodstream. As a result, you could be missing out on its advantages to health. However, adding black pepper can help. Research supports that combining the piperine in black pepper with the curcumin in turmeric enhances curcumin absorption by up to 2,000%.
Caution with supplements: Turmeric supplements are unsafe if you are pregnant, breastfeeding, or have certain conditions such as gallbladder disease, kidney stones, bleeding disorders, diabetes and iron-deficiency. Supplements can also interact with blood thinners and diabetes medications. However, turmeric is generally recognized as safe by the FDA when used as a spice in food.
Summary
As part of our weekly pattern of eating, try to include a variety of plant foods to increase your phytonutrients including polyphenols with antioxidant activity to help “fight” the reactive oxygen species (i.e., oxidative stress) and inflammation. These include
○ Vegetables (purple and red)
○ Fruit (berries, grapes)
○ nuts/seeds
○ beans/lentils including soy
○ herbs and spices
○ Dark Chocolate
References
Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxid Med Cell Longev. 2016;2016:7432797. doi: 10.1155/2016/7432797. Epub 2016 Sep 22. PMID: 27738491; PMCID: PMC5055983.
Bhullar KS, Rupasinghe HP. Polyphenols: multipotent therapeutic agents in neurodegenerative diseases. Oxid Med Cell Longev. 2013;2013:891748. doi: 10.1155/2013/891748. Epub 2013 Jun 6. PMID: 23840922; PMCID: PMC3690243.
Bakoyiannis I, Daskalopoulou A, Pergialiotis V, Perrea D. Phytochemicals and cognitive health: Are flavonoids doing the trick? Biomed Pharmacother. 2019 Jan;109:1488-1497. doi: 10.1016/j.biopha.2018.10.086. Epub 2018 Nov 14. PMID: 30551400.
Pohl F, Kong Thoo Lin P. The Potential Use of Plant Natural Products and Plant Extracts with Antioxidant Properties for the Prevention/Treatment of Neurodegenerative Diseases: In Vitro, In Vivo and Clinical Trials. Molecules. 2018 Dec 11;23(12):3283. doi: 10.3390/molecules23123283. PMID: 30544977; PMCID: PMC6321248.
Omar SH, Scott CJ, Hamlin AS, Obied HK. The protective role of plant biophenols in mechanisms of Alzheimer's disease. J Nutr Biochem. 2017 Sep;47:1-20. doi: 10.1016/j.jnutbio.2017.02.016. Epub 2017 Mar 3. PMID: 28301805.
Han X, Shen T, Lou H. Dietary Polyphenols and Their Biological Significance. Int J Mol Sci. 2007 Sep 12;8(9):950–88. PMCID: PMC3871896.
Mishra A., Sharma A. K., Kumar S., Saxena A. K., Pandey A. K. Bauhinia variegata leaf extracts exhibit considerable antibacterial, antioxidant, and anticancer activities. BioMed Research International. 2013;2013:10. doi: 10.1155/2013/915436.915436
Tapiero H, Tew KD, Ba GN, Mathé G. Polyphenols: do they play a role in the prevention of human pathologies? Biomed Pharmacother. 2002 Jun;56(4):200-7. doi: 10.1016/s0753-3322(02)00178-6. PMID: 12109813.
Oxidative Stress. Helmut Sies, in Stress: Physiology, Biochemistry, and Pathology, 2019. Retrieved from: https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/oxidative-stress
Kumar A, P N, Kumar M, Jose A, Tomer V, Oz E, Proestos C, Zeng M, Elobeid T, K S, Oz F. Major Phytochemicals: Recent Advances in Health Benefits and Extraction Method. Molecules. 2023 Jan 16;28(2):887. doi: 10.3390/molecules28020887. PMID: 36677944; PMCID: PMC9862941.
Holland TM, Agarwal P, Wang Y, Leurgans SE, Bennett DA, Booth SL, Morris MC. Dietary flavonols and risk of Alzheimer dementia. Neurology. 2020 Apr 21;94(16):e1749-e1756. doi: 10.1212/WNL.0000000000008981. Epub 2020 Jan 29. PMID: 31996451; PMCID: PMC7282875.
Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA. Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer's disease. J Nutr Biochem. 2009 Apr;20(4):269-75. doi: 10.1016/j.jnutbio.2008.03.002. Epub 2008 Jul 7. PMID: 18602817; PMCID: PMC2737260.
Boespflug EL, Eliassen JC, Dudley JA, Shidler MD, Kalt W, Summer SS, Stein AL, Stover AN, Krikorian R. Enhanced neural activation with blueberry supplementation in mild cognitive impairment. Nutr Neurosci. 2018 May;21(4):297-305. doi: 10.1080/1028415X.2017.1287833. Epub 2017 Feb 21. PMID: 28221821; PMCID: PMC6093614.
Yang, W., Cui, K., Li, X. et al. Effect of Polyphenols on Cognitive Function: Evidence from Population-based Studies and Clinical Trials. J Nutr Health Aging 25, 1190–1204 (2021). https://doi.org/10.1007/s12603-021-1685-4
Ahmed T, Javed S, Tariq A, Onofrio G, Daglia M, Fazel Nabavi S, Mohammad Nabavi S. Daidzein and its Effects on Brain. Current medicinal chemistry. 2017 Feb 1;24(4):365-75.
The Nutrition Source from the Harvard T Chan School of Public Health. Straight Talk About Soy. Retrieved from https://www.hsph.harvard.edu/nutritionsource/soy/
Jang CH, Oh J, Lim JS, Kim HJ, Kim JS. Fermented soy products: Beneficial potential in neurodegenerative diseases. Foods. 2021 Mar;10(3):636.
Socci V, Tempesta D, Desideri G, De Gennaro L, Ferrara M. Enhancing Human Cognition with Cocoa Flavonoids. Front Nutr. 2017 May 16;4:19. doi: 10.3389/fnut.2017.00019. PMID: 28560212; PMCID: PMC5432604.
Gottumukkala RV, Nadimpalli N, Sukala K, Subbaraju GV. Determination of Catechin and Epicatechin Content in Chocolates by High-Performance Liquid Chromatography. Int Sch Res Notices. 2014 Oct 28;2014:628196. doi: 10.1155/2014/628196. PMID: 27379336; PMCID: PMC4897191.
Tuck KL, Hayball PJ. Major phenolic compounds in olive oil: metabolism and health effects. J Nutr Biochem. 2002 Nov;13(11):636-644. doi: 10.1016/s0955-2863(02)00229-2. PMID: 12550060.
Velmurugan BK, Rathinasamy B, Lohanathan BP, Thiyagarajan V, Weng CF. Neuroprotective Role of Phytochemicals. Molecules. 2018 Sep 27;23(10):2485. doi: 10.3390/molecules23102485. PMID: 30262792; PMCID: PMC6222499.
Rigacci S. Olive Oil Phenols as Promising Multi-targeting Agents Against Alzheimer's Disease. Adv Exp Med Biol. 2015;863:1-20. doi: 10.1007/978-3-319-18365-7_1. PMID: 26092624.
Cao W, Dou Y, Li A. Resveratrol Boosts Cognitive Function by Targeting SIRT1. Neurochem Res. 2018 Sep;43(9):1705-1713. doi: 10.1007/s11064-018-2586-8. Epub 2018 Jun 25. PMID: 29943083.
Witte AV, Kerti L, Margulies DS, Flöel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014 Jun 4;34(23):7862-70. doi: 10.1523/JNEUROSCI.0385-14.2014. PMID: 24899709; PMCID: PMC6608268.
Simona Birtić, Pierre Dussort, François-Xavier Pierre, Antoine C. Bily, Marc Roller,
Carnosic acid, Phytochemistry, Volume 115, 2015, Pages 9-19,
Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD. The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review. Oxid Med Cell Longev. 2016;2016:8590578. doi: 10.1155/2016/8590578. Epub 2016 Dec 27. PMID: 28116038; PMCID: PMC5223034.
Moss M, Oliver L. Plasma 1,8-cineole correlates with cognitive performance following exposure to rosemary essential oil aroma. Ther Adv Psychopharmacol. 2012 Jun;2(3):103-13. doi: 10.1177/2045125312436573. PMID: 23983963; PMCID: PMC3736918.
Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Ann Indian Acad Neurol. 2008 Jan;11(1):13-9. doi: 10.4103/0972-2327.40220. PMID: 19966973; PMCID: PMC2781139.
Sahdeo Prasad and Bharat B. Aggarwal. Chapter 13 Turmeric, the Golden Spice Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK92752/
Ng TP, Nyunt MSZ, Gao Q, Gwee X, Chua DQL, Yap KB. Curcumin-Rich Curry Consumption and Neurocognitive Function from 4.5-Year Follow-Up of Community-Dwelling Older Adults (Singapore Longitudinal Ageing Study). Nutrients. 2022 Mar 11;14(6):1189. doi: 10.3390/nu14061189. PMID: 35334842; PMCID: PMC8952785.
Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017 Oct 22;6(10):92. doi: 10.3390/foods6100092. PMID: 29065496; PMCID: PMC5664031.