Beneficial (and some negative) Plant/Natural Chemicals
This page is under construction
Introduction to plants and their chemicals
The expression, “Let Food be Thy Medicine” is a famous quote by the Greek physician Hippocrates (c. 460 – c. 370 BC). But which foods?
Plants and their compounds can certainly have beneficial effects. Herbs and herbal remedies have been used for thousands of years in traditional medicine for various conditions in a safe and effective manner. Some of the qualities being anti-inflammatory, anti-carcinogenic, anti-atherosclerotic, antibacterial, antimitotic, anti-inflammatory, analgesic, local anesthetic, hypnotic, psychotropic, and antitumor activity, antifungal antibacterial, antiviral, cholesterol-lowering inflammatory, antihypertensive, vasodilator effects, antiobesity, antihypercholesterolemic and antiatherosclerotic activities.
But just because something comes from a plant, doesn’t automatically mean it’s good for you. Depending on the particular compound, it can be beneficial, neutral, or even negative. Some plant chemicals are beneficial unless you ingest too much. Some have beneficial and detrimental chemicals in the same plant.
And the terms used: polyphenol, resveratrol, flavonoid, lectin, oxylates, etc. can make a head spin!
Vegetables do often contain toxins and anti-nutrients that interfere with the absorption of nutrients. The toxins are natural defenses that the plant uses to ward off the insects, predators, and fungi that might attack it. Fortunately, many toxins can be deactivated with proper cooking.
Additionally, new world fruits and vegetables have posed a very recent introduction to the vast majority of world population, that is except for the native Americans. Until the explorers introduced them, no European, African or Asian had ever been exposed to them, which means, their body, gut bacteria, and immune system were ill-prepared to tolerate them, although the response from the body is often subtle to imperceptible. Such negative (albeit subtle to imperceptible) responses often extend to this date as this introduction happened 500 years ago, which put into perspective is trifling in comparison to the entire human evolution timeline, suggesting we still haven’t adjusted to them. New world fruits and vegetables include foods from the bean family (legumes, peanuts, cashews), grains, pseudo-grains such as amaranth and quinoa, the squash family (pumpkins, acorn squash, zucchini) as well as chia and certain seeds.
But especially for APOE4s, there are beneficial compounds that come from plants. Certain phytochemicals have antioxidant, anti-inflammatory, anti-amyloid, and anticholinesterase properties - the four fundamental pillars identified in the process of Alzheimer’s.
ADD GRAPHIC - NATURAL PRODUCTS AND AD Caption: Neuroprotective effects from natural products. Source: Neuroprotective Natural Products for Alzheimer’s Disease (Xin Chen et al, 25 May 2021)
Phytochemicals can offer neuroprotective effects which not only act at the level of blocking the progression of Alzheimer’s but also aid in Alzheimer’s prevention. By incorporating natural compounds with other therapeutic interventions, the onset or progression of Alzheimer’s could be dramatically reduced, counteracting the estimate that the number of people with dementia will nearly triple to more than 152 million by 2050. [Source: Global dementia cases forecasted to triple by 2050 (Alzheimer's Association, 27 Jul 2021)]
This is not a comprehensive article but an attempt to condense and simplify the subject as well as cover studies of particular interest to APOE4s regarding phytochemicals with emphasis on Alzheimer’s Disease.
ADD GRAPHIC – MECHANISMS OF PHYTOCHEMICALS IN AD Phytochemicals can aid the brain in many ways. Source: Figure 1 from Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation(Javad Sharifi-Rad et al, 12 Aug 2022)
Polyphenols
Polyphenols are a group of compounds found in plant foods that are beneficial for health. Polyphenols are how fruits, berries, and vegetables get their vibrant colors and determines their taste and aroma. Over 8,000 polyphenols have been discovered. They're naturally found in many plant-based foods like fruits, vegetables, herbs, tea, red wine, and dark chocolate. Most of the health benefits of polyphenols relate to their role as an antioxidant.
Through the antioxidant property, they help protect the body and neutralize free radicals that cause damage to cells. Free radicals are highly reactive oxygen molecules produced by normal cell processes and external factors like radiation, air pollution, smoking, and chemical exposure. Without antioxidants to neutralize free radicals, cells are injured increasing health problems.
ADD GRAPHIC - OXIDATIVE STRESS Caption: Without antioxidants to counter free radicals, damaging oxidative stress occurs unleashing an inflammatory cascade.
Free radicals are highly reactive oxygen molecules produced by normal cell processes and external factors like radiation, air pollution, smoking, and chemical exposure. Without antioxidants to neutralize free radicals, cells are injured, increasing your risk of health problems like diabetes, heart disease, and cancer.
Antioxidants and polyphenols are often considered to be the same thing, but technically, it’s many of the polyphenols that contain antioxidants.
Researchers have identified the role polyphenols play in delaying the onset of dementia and reducing the risk for Alzheimer's. For example, resveratrol, found in grape skins and red wine, has been found to have neuroprotective effects. Other studies have demonstrated a reduction in the progression of dementia when polyphenols were included in the daily diet, through changes in the neurological system leading to dementia.
Among the many potential health benefits of polyphenols, those of interest to APOE4s include:
- Lower Blood Sugar Levels
- Increase Insulin Sensitivity
- Reduce Inflammation
- Improve Heart Health
- Boost Brain Function
Why the name polyphenol? Polyphenols are characterized by the existence of more than one phenol unit — or building block — per molecule. That's what makes them poly- (many) phenols. There's another name for polyphenols — phenolics.
Want to know the polyphenol content of certain foods? Go to Phenol-explorer. At the writing of this wiki, Phenol-explorer is a database that contains more than 35,000 content values for 500 different polyphenols in over 400 foods. These data are derived from the systematic collection of more than 60,000 original content values found in more than 1,300 scientific publications. Each of these publications has been critically evaluated before inclusion in the database. The whole data on the polyphenol composition of foods is available for download.
ADD GRAPHIC - Screen shot from phenol explorer caption: Just one screen shot of the many ways to sort and view the database of foods and polyphenols from Phenol-explorer
The Phenol-explorer database is comprehensive and likely more information than most people need, so for a quick reference here’s a list of Polyphenol-Rich Foods. [Source: 64 Foods High in Polyphenols (Ashley Braun, 9 Feb 2022) Vegetables high in polyphenols
- Broccoli
- Carrots
- Spinach
- Red lettuce
- Onions
- Asparagus
- Artichokes
- Shallots
- Garlic
Fruits high in polyphenols (but watch the glycemic load)
- Blueberries
- Strawberries
- Raspberries
- Blackberries
- Cranberries
- Grapes
- Cherries
- Lemon
- Grapefruit
- Oranges
- Pears
- Apples
- Peaches
- Plums
- Pomegranate
- Nectarine
- Apricots
- Olives and olive oil
Nuts and Seeds high in polyphenols
- Walnuts
- Almonds
- Flaxseed
- Chia seeds
- Pecans
- Chestnuts
- Hazelnuts
Herbs and Spices high in polyphenols
- Turmeric
- Cinnamon
- Cumin
- Cloves
- Celery seed
- Basil
- Ginger
- Marjoram
- Parsley
- Peppermint
- Oregano
- Rosemary
- Sage
- Thyme
- Lemon verbena
Other foods and drinks high in polyphenols
- Green tea
- Black tea
- Red wine
- Dark chocolate
- Cocoa powder
- Coffee
- Vinegar
Keep sources of polyphenols consumed varied. This aligns with the feeding habits of our hunter-gathers ancestors. “Ancient foragers regularly ate dozens of different foodstuffs. … This variety ensured that the ancient foragers received all the necessary nutrients.”[Source: the book, Sapiens: A Brief History of Humankind by Yuval Noah Harari, PhD, page 59, kindle location 854 of 7356].
Dr Teri Wahls, in her book, The Wahls Protocol, describes how she repaired her cells by following a diet similar to how our ancestors ate (Paleo). Among her recommendations, she recommends a varied balance of different types of vegetables and fruits daily, including greens (kale, collards, chard, lettuce-darker the better, etc), deeply colored (beets, carrots, etc.), and rich in sulfur (cauliflower, broccoli, cabbage, asparagus, brussel sprouts, turnips, radishes, onions, garlic, etc). For more information on Dr Wahl’s approach see Mitochondria. Also refer to the ApoE4.info podcast with her, which includes show notes, Heal Neurodegeneration w/ Paleo Principles
Subcategories of Polyphenols
Polyphenols are divided into four main categories:
- flavonoids
- stilbenes
- lignans
- phenolic acids
Some of those categories can be broken down into additional subgroups.
ADD GRAPHIC on Polyphenols CAPTION The four main categories of polyphenols with a further breakdown of flavonoids.
Flavanoids
Flavanoids are a class of polyphenol rich in antioxidant activity. Flavonoids help regulate cellular activity and fight off the free radicals that cause oxidative stress on your body. Allergens, germs, toxins, and other irritants can trigger inflammation that results in uncomfortable symptoms. Flavonoids may help your body dismiss that inflammatory reaction so that those symptoms are reduced.
Flavanoids include: flavonols, flavones, flavanones, flavanols or flavan-3-ols, anthocyanins, and isoflavonoids.
Flavonols. Flavonols are the largest subclass of the flavonoids. Flavonols exist in many colors varying from white to yellow, and they are closely related in structure to the flavones. Flavonols are represented mainly by quercetin, kaempferol, and myricetin. Flavonols have many benefits to human health because they have antioxidant, neuroprotective properties, in addition to their effects in prevention of atherosclerosis and other vascular diseases.
Flavones. Flavones are closely related in structure to the flavonols. Both in vitro and in vivo to have shown neuroprotective effects. Flavones are common in foods, mainly from spices, and some yellow or orange fruits and vegetables.
Flavanones. Flavanones are another important class which is generally present in all citrus fruits. Epidemiological studies reported an inverse relationship between their intake and the risk of cardiovascular diseases. Clinical and experimental data further showed their antihypertensive, lipid-lowering, insulin-sensitizing, antioxidative, and anti-inflammatory properties, which could explain their antiatherogenic action in animal model.
Flavanols. Flavanols or flavan-3-ols is a class of flavonoid. They represent the most common flavonoids consumed in the American diet. Tea, chocolate, grapes, apples, and red wine are some of the prominent sources of these polyphenols.
ADD GRAPHIC - Caption sources with top flavanol levels
Anthocyanins. These flavonoids are water-soluble pigments. They are responsible for the colors, red, purple, and blue, are in fruits and vegetables. Berries, currants, grapes, and some tropical fruits have high anthocyanins content. Red to purplish blue-colored leafy vegetables, grains, roots, and tubers are the edible vegetables that contain a high level of anthocyanins.
Isoflavonoids. Isoflavonoids are structurally similar to estrogens, exerting both estrogenic and antiestrogenic properties in various tissues. Some studies support the notion of a protective effect of their consumption in immunomodulation, cognition, risk reduction of certain cancers, cardiovascular and skin diseases, osteoporosis and obesity, as well as relief of menopausal symptoms. [Source: Isoflavonoids – an overview of their biological activities and potential health benefits (Eva Miadoková, Dec 2009) ]
Stilbenes
Abundant in grapes, berries, and conifer bark waste stilbenes, a diverse group of natural defense phenolics, may confer a protective effect against aging-related diseases.
Resveratrol is a well-known polyphenol which is found mainly in the skin of grapes; it has attracted extensive scientific attention due to its potential health benefits related with its cardiovascular (French paradox), chemopreventive, antiobesity, antidiabetic, and neuroprotective properties. However, recent data have highlighted that also other stilbene compounds such as pterostilbene may have higher bioavailability and possess better neuroprotective activity against AD than resveratrol. [Source: Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases (Mika Reinisalo et al, 9 Jun 2015)]
Lignans
Lignans are a large group of low molecular weight polyphenols found in plants, particularly seeds, whole grains, and vegetables. The name derives from the Latin word for "wood". Lignans are precursors to phytoestrogens with weakly estrogenic and anti-estrogenic properties.
Health benefits attributed to lignans have included a lowered risk of heart disease, menopausal symptoms, osteoporosis and breast cancer.
The highest concentrations of dietary lignans are found in flaxseed.
Differences in bioavailability of various plant lignans from foods, and variation in enterolignan production among gut microbial communities contribute to large interindividual variation in enterolignan exposure. Consequently, studying associations between lignan exposure and health and disease in humans is challenging. Current evidence suggests a diet rich in lignans may be beneficial, but further research is needed to characterize the specific role of lignans.
Phenolic Acids
Phenolic acid accounts for about 30% of all known polyphenols. Phenolic acids are commonly found and well documented for health protective effects like antimicrobial, anticancer, anti-inflammatory, anti-mutagenic, and more. Phenolic acid is found in foods like grapes, berries, pomegranates, walnuts, chocolate, coffee, and green tea. The key advantage of using phenolic acids is their metabolizing ability by natural microbes; therefore provide an essential alternate to man-made chemicals which are harmful to environment also.
INSERT GRAPHIC - applications of phenolic acids CAPTION: Different applications of phenolic acids. [Source: Figure 4 from Phenolic acids: Natural versatile molecules with promising therapeutic applications (Naresh Kumar and Nidhi Goel, 20 Aug 2019)]
For more information on phenolic acids, see Phenolic acids: Natural versatile molecules with promising therapeutic applications(Naresh Kumar and Nidhi Goel, 20 Aug 2019)
Isothiocyanates
Isothiocyanates are a very important group of biologically active compounds. Isothiocyanates are toxic defensive chemicals against invading organisms such as herbivores, insects, and microorganisms.
In organisms like humans, isothiocyanates are detoxified by conjugation with glutathione.
Isothiocyanates are mainly produced by cruciferous species. Numerous scientific studies have established that consumption of large amount of cabbages, broccoli, cauliflower, and brussels sprouts is associated with a decreased risk of carcinomas of the lung, stomach, colon, and rectum.
In cultured cells and animal models, isothiocyanates also exhibited antioxidant and anti-inflammatory activities.
For more information on isocyanates, visit Isothiocyanates
Alkaloids
Alkaloids are produced by a large variety of organisms including bacteria, fungi, plants, and animals.
Medical use of alkaloid-containing plants has a long history. They have diverse physiological effects: antibacterial, antimitotic, anti-inflammatory, analgesic, local anesthetic, hypnotic, psychotropic, and antitumor activity and many others.
Most plants contain several alkaloids. Most of the known functions of alkaloids are related to protection. the presence of alkaloids in the plant prevents insects and animals from eating it. However, some animals are adapted to alkaloids and even use them in their own metabolism.
Such alkaloid-related substances as serotonin, dopamine and histamine are important neurotransmitters in animals.
The anticholinesterase activity of alkaloids, together with their structural diversity and physicochemical properties, makes them good candidate agents for the treatment of AD.
For greater investigation of this subject, see Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer's disease(Eduardo Luis Konrath et al, Dec 2013)
Cannabinoids
Cannabinoids interact with the body’s endocannabinoid system (endo = internal). The endocannabinoid system (ECS) is responsible for a variety of physiological and cognitive processes. The body produces its own endocannabinoids.
Phytocannabinoids are cannabinoids obtained by plants, cannabis plants primarily. At least 85 different cannabinoids have been isolated from the cannabis plant. The two cannabinoids usually produced in greatest abundance are cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). THC is the cannabinoid that produces the "high" from consuming marijuana.
Cannabinoids interact with the body’s cannabinoid receptors to regulate a variety of functions in the body, such as inflammation, pain perception, mood, and memory.
Cannabis has been used as medicine for thousands of years, but experts are still trying to fully understand the endocannabinoid system. The efficacy of cannabinoids with Alzheimer’s or cognitive issues is not yet well elucidated.
For a deeper discussion, see Cannabinoids, Cannabidiol (CBD), THC, HEMP, Marijuana, Cannabis