Updates in Neurology:
The Neuroprotective Role of Dietary PolyphenolsThis section is compiled by Frank M. Painter, D.C.
Send all comments or additions to: Frankp@chiro.org
FROM: Restorative Medicine Digest; 2021 (Feb 11) ~ FULL TEXT
Liz Sutherland, NDPolyphenols are a group of naturally occurring bioactive compounds found in high amounts in many fruits, vegetables, seeds, nuts, herbs, and spices. It’s been known for a while that polyphenols are important antioxidants. For example, the dopamine-preserving effect of catechin-rich polyphenol extracts from green tea observed in animal models of Parkinson’s disease, is thought to be due in part to the ability of polyphenols to modulate the antioxidant activity of superoxide dismutase. [1] Now, an increasing number of studies suggest that dietary polyphenols have potent anti-inflammatory and neuroprotective properties as well. In particular, studies report that polyphenols protect neurons from neurotoxins; modulate neuroinflammation; and improve memory, learning, and cognitive function. The traditional Mediterranean diet is very rich in polyphenol-containing plant foods, which is one reason it’s thought to offer protection against neurodegeneration and cognitive decline.
Dietary Polyphenols and Neuroprotection
Neuroinflammation is a common feature of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Multiple Sclerosis. Persistent oxidative stress is known to play a significant role in the neurodegenerative process (as well as in the aging process in general). It makes sense, then, that polyphenols could have neuroprotective effects in their capacity as powerful antioxidants, but it turns out in addition to being free-radical scavengers, they influence a variety of molecular mechanisms including gene expression. In vitro and animal studies show that polyphenols are able to: [2]
Decrease neuroinflammation
Protect against beta-amyloid plaque formation
Protect against neuronal damage from glutamate toxicity
Promote synaptic plasticity and nerve growth
Human studies have also shown benefits, including improving cognitive performance. [3]
In fact, benefits observed in human studies have been attained from using amounts of polyphenols akin to levels that would be available from the diet. [4]
Polyphenols and Microglial Cells
Neuroinflammation is a critical aspect of the brain’s defense mechanisms, but when it’s excessive or unresolved it contributes to the underlying neuronal loss and damage characteristic of neurodegenerative disorders. Neuroinflammation activates microglial cells, which are a foremost component of the brain’s innate immune response. Recent studies have highlighted an intriguing property of activated microglial cells: they can be induced into two different forms or phenotypes depending on the predominant needs of the CNS environment in which they find themselves. This means they can shift into having either pro-inflammatory/neurotoxic or anti-inflammatory/neuroprotective effects. Amazingly, dietary polyphenols are able to influence microglial cells to shift in the direction of being the resolving rather than the activated phenotype. As a result, microglial cells will produce anti-inflammatory cytokines and contribute to neuroregeneration. [5]
Types of Polyphenols
Polyphenols comprise an enormous set of plant compounds. Over 8,000 types have been identified so far. For simplicity, polyphenols can be divided into two major categories: flavonoids and nonflavonoids.Flavonoids Over 4,000 distinct flavonoids are known at this point, and they account for 50 to 60% of all polyphenol compounds. Some well-known flavonoids include luteolin, quercetin, genistein, hesperetin, and catechins (often referred to as proanthocyanidins).
Nonflavonoids This group includes resveratrol, which is found in grapes and wine; stilbenes and lignans, found in fruits, vegetables, seeds, and whole grains; capsaicinoids found in chili peppers; and curcumin found in turmeric. [6]
Dietary Sources of Polyphenols Culinary and medicinal plants and spices are great dietary sources of polyphenols.
In a study that identified the 100 foods richest in polyphenols, cloves came out on top.
Other dietary sources all of which were high up on this list include cocoa powder, blueberries, blackberries, strawberries, red raspberries, black currants, plums, sweet cherries, apples, pomegranate juice, black beans, white beans, chocolate, green tea, and black tea. [7]
Let’s focus now on some specific dietary polyphenols.Isoflavones Isoflavones are mostly found in the leguminous family of plants. Dietary sources high in isoflavones include beans (particularly soybeans), chickpeas, pistachios, split peas, lima beans, fava beans, lentils, green tea, and flaxseeds. [8]
Nuts Many nuts, including hazelnuts, almonds, pecans, and walnuts are excellent sources of polyphenols. [9, 10]
Nettles (Urtica dioica) The aerial parts of the nettle plant are rich sources of polyphenols. In an animal study, nettle supplements and regular swimming exercise were shown to improve the adverse effect of brain injury. The analysis showed that nettle supplementation had an antioxidant effect, and also down-regulated inflammatory transcription factors, as well as promoting learning. [11]
Quercetin Quercetin has been shown to improve memory, learning, and cognitive functions in several in vitro and animal models. [12]
Rosmarinic Acid Rosmarinic acid is a polyphenol compound present in plants such as rosemary, sage, lemon balm, mint, and sweet basil. A growing body of research suggests that rosmarinic acid may be protective against neuronal cell death and beta-amyloid plaque formation. [13]
Curcumin Curcumin is a polyphenol compound found in turmeric (Curcuma longa), that has been studied extensively for its systemic anti-inflammatory properties. Curcumin also appears to prevent the amyloid plaque deposition associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In addition, it decreases neuroinflammation through a variety of mechanisms including inhibiting proliferation of microglial cells, and reducing levels of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6). [14]
Curcumin is more lipophilic than hydrophilic, which allows it to be absorbed through the blood-brain barrier. It is better absorbed when eaten with fat, and can be detected in the cerebrospinal fluid. [15] Curcumin and turmerone are the major bioactive compounds of Curcuma longa. Although tumerone is not technically a polyphenol, it may promote the production of neural stem cells thereby enhancing neuron generation and repair. [16]
Resveratrol Resveratrol is a polyphenol found in highest concentrations in the skin and seeds of berries and grapes, and consequently, in red wine (and to a lesser extent in rose and white wine).
Rich sources of polyphenols include herbs, spices, berries, tea, cocoa, dark chocolate, ground flaxseeds, chestnuts, pecans, almonds (with skin), and many other plant foods. A number of different types of berries are rich in polyphenols, including blueberries, blackberries, strawberries, and raspberries. Resveratrol has been shown to inhibit the formation of beta-amyloid plaque, [17] and to promote remyelination in an animal model of MS. [18]
Bioavailability of Dietary Polyphenols
The physiological activity of polyphenols is influenced by several factors including the health of a person’s metabolism, intestinal absorption, and the bioavailability of the polyphenol itself. Gut bacteria ferment polyphenols to produce short-chain fatty acids, which themselves have neuromodulatory effects. It also appears that polyphenols can cross the blood-brain-barrier, and as a result, may have direct neuroprotective and neuromodulatory effects within local brain tissue. There is certainly enough growing evidence of their protective effects for you to advise your patients with neuroinflammatory and neurodegenerative conditions to incorporate foods and beverages high in polyphenols into their health and wellness lifestyle choices. [19]
References
Neuroprotective Properties of Green Tea (Camellia sinensis) in Parkinson’s Disease: A Review
Molecules 2020 (Sep); 25 (17): 3926Dietary Polyphenols as Modulators of Brain Functions: Biological Actions
and Molecular Mechanisms Underpinning Their Beneficial Effects
Oxidative Medicine and Cellular Longevity 2012; 2012: 914273Chapter 2 - Blueberry Polyphenols and Neuroprotection
Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease:
Prevention and Therapy 2015, Pages 17-28Dietary Polyphenols as Modulators of Brain Functions: Biological Actions
and Molecular Mechanisms Underpinning Their Beneficial Effects
Oxidative Medicine and Cellular Longevity 2012; 2012: 914273Phenolic Compounds Characteristic of the Mediterranean Diet in Mitigating
Microglia-Mediated Neuroinflammation
Frontiers in Cellular Nuroscience 2018 (Oct 23); 12: 373Chemistry and Biochemistry of Dietary Polyphenols
Nutrients 2010 (Dec); 2 (12): 1231–1246Identification of the 100 Richest Dietary Sources of Polyphenols:
An Application of the Phenol-Explorer Database
European Journal of Clinical Nutrition 2010 (Nov); 64 Suppl 3: S112-20Bioavailability of Dietary Flavonoids and Phenolic Compounds
Molecular Aspects of Medicine 2010 (Dec); 31 (6): 446-67Nuts, Especially Walnuts, Have Both Antioxidant Quantity and Efficacy
and Exhibit Significant Potential Health Benefits
Food & Function 2012 (Feb); 3 (2): 134-40Health Benefits of Walnut Polyphenols: An Exploration Beyond Their Lipid Profile
Critical Reviews in Food Science and Nutrition 2017 (Nov 2); 57 (16): 3373-3383The Beneficial Effects of Nettle Supplementation and Exercise
on Brain Lesion and Memory in Rat
Journal of Nutritional Biochemistry 2009 (Dec); 20 (12): 974-81Neuroprotective Effects of Quercetin in Alzheimer’s Disease
Biomolecules. 2020 (Jan); 10 (1): 59The Therapeutic Potential of Rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer's Disease
Evid Based Complement Alternat Med 2016; 2016: 2680409Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways
in Treating Age-Related Neurodegenerative Diseases
International J of Molecular Sciences 2018 (Jun); 19(6): 1637The Effect of Curcumin (turmeric) on Alzheimer's disease: An Overview
Annals of Indian Academy of Neurology 2008 (Jan); 11 (1): 13–19Aromatic-turmerone Induces Neural Stem Cell Proliferation in Vitro and in Vivo
Stem Cell Research & Therapy 2014 (Sep 26); 5 (4): 100Resveratrol and Alzheimer’s disease: Message in a Bottle on Red Wine and Cognition
Frontiers in Aging Neuroscience 2014; 6: 95Resveratrol Promotes Remyelination in Cuprizone Model of
Multiple Sclerosis: Biochemical and Histological Study
Mol Neurobiol 2017 (Jul); 54 (5): 3219-3229Phenolic Compounds Characteristic of the Mediterranean Diet
in Mitigating Microglia-Mediated Neuroinflammation
Frontiers in Cellular Neuroscience 2018; 12: 373
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