What Are Flavonoids In CBD?

What are flavonoids in CBD and what do they do? Currently, scientists are aware of approximately 6000 flavonoids that contribute to the colorful pigments of fruits, herbs, vegetables, and medicinal plants.3

Flavonoids are a group of natural chemical substances called secondary metabolites. Chemically, they are characterized as a chemical compound that has a hydroxyl group linked directly to a benzene ring. That sounds complex, but flavonoids are simple compounds found in fruits, vegetables, grains, bark, roots, stems, flowers, tea, and wine.

Introduction

Flavonoids are well known for their health benefits, and there is a rising interest in isolating them for use in nutraceutical, pharmaceutical, medicinal and cosmetic applications.3

Flavonoid benefits range from antioxidant activity, anti-inflammatory activity, antimutagenic activity, and anticarcinogenic properties. Flavonoid’s ability to modulate key cellular enzyme functions may benefit diseases such as cancer, Alzheimer’s disease (AD), atherosclerosis, and others. Research on flavonoids is getting more and more attention as they gain a reputation for sharing the same excitement as CBD benefits.

Where Are Flavonoids Found?

Flavonoids are found through several parts of plants and are present in many plant species.3 They can also be found in foods and beverages made from those plants. Their natural purpose in many plants, like vegetables, is often to promote growth and defend the plant from illness or injury. In flowers, including products like CBD flower, flavonoids may also be present as pigments.

Throughout the plant, kingdom flavonoids are recognized widely as compounds that are responsible for colors and aromas that help plants survive and continue their species through the next generation of seeds.

Plant Flavonoids

  • Pigments and aromas that attract pollinators
  • Pigments that filter harmful UV light
  • Flavors that encourage seed dispersal or deter herbivory
  • Antioxidants and antibacterial compounds that defend from illness
  • Encourage frost hardiness and heat tolerance
  • Act as signaling molecules in plant cell communication

Health Benefits

Flavonoids have many health-promoting effects that benefit humans, as well. They are antioxidative, anti-inflammatory, anti-mutagenic, and have anti-carcinogenic properties.3 Flavonoids also have been known for the ability to modulate key cellular enzyme functions and can strongly inhibit several enzymes, such as xanthine oxidase (XO), cyclo-oxygenase (COX), lipoxygenase and phosphoinositide 3-kinase.

Here are some of the potential benefits of flavonoids:

  • Antioxidant activity
  • Anti-inflammatory
  • Anti-mutagenic Anti-carcinogenic
  • Modulation of cellular enzyme functions
  • Antimicrobial and antiviral activity
  • Anti-allergenic
  • Anti-inflammatory
  • Vasodilating activity

Flavonoid Types

Flavonoids have several subgroups, including chalcones, flavones, flavonols, and isoflavones.3 These subgroups have unique sources such as flavonols and flavones, from onions and tea. Researchers believe that flavonoids may have health applications in humans and animals like chemoprevention, treating Alzheimer’s disease, and broad dietary and health benefits. Flavonoids may also have applications in agriculture and could provide new techniques for pest management.

Flavonols

Flavonols occur abundantly in many fruits and vegetables. The most popular flavonols are kaempferol, quercetin, myricetin, and fisetin.3 Primary sources of flavonols include tea, red wine, onions, kale, lettuce, tomatoes, apples, grapes, and berries. Flavonols are known for a wide range of health benefits, including antioxidant activity and reduced risk of vascular disease.

Flavanones

Flavanones are another essential class of flavonoids that are present in almost all citrus fruits such as oranges, lemons, and grapes.3 Hesperidin, naringenin, and eriodictyol are examples of flavonones, which impart the bitter taste found in citrus juices and peels.

Flavonones can have wide-ranging health benefits because of their ability to scavenge free radicals that can damage cells. Citrus derived flavonoids have many health-promoting benefits like antioxidant activity, anti-inflammatory activity, blood lipid-lowering, and cholesterol-lowering.

Flavones

Flavones area major subgroups of flavonoids, they are widely present in leaves, flowers, and fruits as compounds called glucosides.3 Celery, parsley, red peppers, chamomile, mint, and Ginkgo Biloba are some of the primary sources of flavones. Some popular flavones include luteolin, apigenin, and tangeritin. The peels of citrus fruits are abundant in the flavones tageretin, nobiletin, and sinensetin.

Apigenin is the primary anti-anxiety agent found in chamomile and is also common in cannabis.4 It can bind to the same benzodiazepine receptors that are targeted by anti-anxiety drugs but doesn’t produce undesirable side effects like muscular relaxation, amnesia, and sedation.

Apigenin also inhibits the production of tumor necrosis factor-alpha (TNF-α), which is a cytokine that induces and maintains inflammation such as that found in rheumatoid arthritis and multiple sclerosis.4

Isoflavonoids

Isoflavonoids are a large and very distinctive subgroup of flavonoids found in soybeans and other leguminous plants.3 While limited among plant species, some Isoflavonoids have been found in microbes. The presence of isoflavonoids in some microbes is not as surprising as you may think as they play a role in developing compounds that plants and microbes use to communicate with each other.

A great potential of Isoflavonoids is their capacity to fight several diseases.3 Isoflavones such as genistein and daidzein are of particular interest because they are able to induce hormonal and metabolic changes that can influence disease pathways.

Anthocyanins

Anthocyanins are pigment flavonoids responsible for colors in plants, flowers, and fruits.3 The color of an anthocyanin depends on pH and its chemical structure. The most common anthocyanin flavonoids include cyanidin, delphinidin, malvidin, pelargonidin, and peonidin, which mostly occur in the outer cell layers of various fruits.

These include fruits such as cranberries, black currants, red grapes, Merlot grapes, raspberries, strawberries, blueberries, bilberries, and blackberries. Anthocyanins are very stable and possess many health benefits which make them a popular dietary ingredient in the food industry.

Other Flavonoids

Neoflavonoids

Neoflavonoids are a chemically unique subgroup of flavonoids.3 The first discovered neoflavonoid was calophyllolide from Calophyllum inophyllum seeds, found in 1951. Calophyllolide is also found in the bark and timber of the native Sri Lankan plant Mesua thwaitesii.

Flavanonols (Catechins)

Flavanonols, also called dihydroflavonols or catechins, are a different chemical form of flavanones.3 Their chemical structure is unique among all the subgroups of flavonoids. Flavanonols are found abundantly in bananas, apples, blueberries, peaches, and pears.

Chalcones

Chalcones are a subclass of flavonoids that includes phloridzin, arbutin, phloretin, and chalconaringenin.3 They occur in significant amounts in tomatoes, pears, strawberries, bearberries, and certain wheat products. Chalcones and derivatives of chalcones have caught a lot of attention because of the numerous nutritional and biological benefits they possess.

What Are Flavonoids Good For?

Cancer Prevention

The ability of flavonoids to scavenge free radicals and act as antioxidants is complemented by the ability of some flavonoids to stop the development of some cancer cells by disrupting their reproduction cycle through regulation of gene expression on oncogenes and tumor-suppressor gene.3 Flavonoids may also help prevent cancer and tumor growth by inducing death in some types of cancer cells, and regulating the metabolism of carcinogens.

Flavonoids such as tannins, stilbenes, curcuminoids, coumarins, lignans, quinones, and other flavonoids have these traits which are called “chemopreventive” as they help in the prevention of some cancers.3 Tangeritin, fisetin, apigenin, luteolin daidzein, and genistein are also thought to have cancer-preventive properties.

The broad antioxidant and anti-inflammatory properties of flavonoids is another trait that makes them a valuable compound in suppressing cancerous cells and tumors and promoting overall health.3 Phenolic types of flavonoids are thought to be especially effectual natural compounds in suppressing inflammation, neutralizing harmful cells and compounds in the body, and preventing damage from carcinogens.

Multiple studies have examined Pelingo apple juice, which is rich in flavonoids and has shown the ability to strongly inhibited breast cancer cell proliferation and tumor cell growth.3 The flavonoids genistein, daidzein, and equol have also been studied for their potential to aid in the treatment of many chronic diseases. These diseases include cancer, cardiovascular disorders, and osteoporosis.

Some flavonoids like estrogen, which are present in fruits and vegetables, tea, red wine, and cereals, are even able to act like steroid hormones to help promote healthy cellular activity.3 Flavonoids have also been researched for their ability to act as antibiotics against drug-resistant bacteria and have been found to have considerable benefits in the treatment of mild to moderate Alzheimer’s disease.

Weight Management

Researchers have found wide-ranging links between intake of specific fruits and vegetables and weight maintenance.1 Increased consumption of most flavonoids has been inversely associated with weight change over four year time intervals (with adjustment for changes in other lifestyle factors). Anthocyanins, flavonoid polymers, and flavonols are the main three types of flavonoids that have been observed in using CBD to lose weight.

Increased dietary intake of foods rich in flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers may help adults maintain their weight, prevent obesity, and related health concerns.1 More intake of blueberries, apples, pears, prunes, strawberries, and grapes has been associated with weight gain. Increased intake of peppers and celery was also associated with less weight gain. Fruits and vegetables that have been associated with less weight gain are plentiful and diverse in flavonoid content, especially flavonols, anthocyanins, and flavones.

Several flavonoid subclasses have been shown to decrease energy intake, increase glucose uptake in muscle, and decrease glucose uptake in fat tissue.1 Studies focusing on green tea which is rich in flavan-3-ol type flavonoids have suggested that some flavonoids may decrease fat absorption, increase energy expenditure, and inhibit fat tissue formation.

Flavonoids in Cannabis

It has been estimated that cannabis leaves have up to 1% flavonoid content.4 The cannabis plant has 23 commonly occurring flavonoids, with C-/O- and O-glycosides of the flavon- and flavonol-type aglycones apigenin, luteolin, quercetin, and kaempferol.2 Orientin, vitexin, luteolin-7-O-glucoside, and apigenin-7-O-glucoside are the major flavonoid glycosides present in low-THC Cannabis strains like hemp. Cannabis also has two unique types of flavonoids called cannflavins A and B. Some flavonoids of cannabis are able to cross cell membranes and remain active in cannabis smoke.4

Flavonoids may alter the way THC and prescription drugs work and are absorbed in the body in a way similar to CBD.4 CBD and flavonoids like naringenin from grapefruit can act on liver enzymes to block the metabolism of cyclosporine, caffeine, benzodiazepines, and calcium antagonists. Therefore, some pharmaceuticals have warnings against consuming grapefruit while taking a medication, and why people taking those medications may also want to avoid taking CBD supplements.

Antioxidant Flavonoids

Apigenin and other flavonoids interact with estrogen receptors and can enter the body through cannabis smoke.4 Apigenin has low estrogenic activity despite having a high affinity for estrogen receptors. Research has observed that apigenin may inhibit estradiol-induced proliferation of breast cancer cells.

Some research even suggests that flavonoids can effectively recycle CBD as an antioxidant and boost the length of time it remains active.4 Antioxidants are significant because they block free radical formation, which can protect the body’s cells from damage and inflammation.

Quercetin is a flavonol found in nearly all vascular plants, including cannabis, which is an antioxidant with more potential potency than ascorbic acid.4 Quercetin and other antioxidants like CBD can work together in synergy to produce even more potent antioxidant action. Through blocking free radical formation, antioxidant flavonoids like quercetin hinder carcinogenesis and inflammatory diseases, and the replication and activation of HIV-1 (4) The milk thistle flavonoid silymarin can act through mechanisms similar to quercetin to suppress hepatitis C virus replication that can lead to hepatic carcinoma.

Quercetin and silymarin can act in synergy with the cannabinoid CBN and counteract the effects of THC.4 Th because THC alone can increase the formation of free radicals that could promote virus replication.

Anti-Anxiety Flavonoids

The flavonoid apigenin shares many extensive health benefits with terpenes, and cannabinoids and is found in almost all vascular plants.2 Its anti-anxiety properties are thought to contribute to the overall anti-anxiety effect of many cannabis strains.

Cannaflavins: Flavonoids Unique to Cannabis

Cannflavin A is one of a pair of flavones unique to cannabis.4 Cannflavin A can be found in levels up to 0.02% of the dry herb weight of cannabis. This unique cannabis flavonoid is a potent inhibitor of the inflammatory factor prostaglandin E2 (PGE2) in human rheumatoid synovial cells. It is thought to be about 30 times more potent than aspirin in the human body. Cannflavin A also inhibits compounds like cyclooxygenase (COX) enzymes and lipoxygenase (LO) enzymes that can cause oxidative damage. THC also has this ability, but research has observed that cannaflavin A is a stronger inhibitor.

Flavonoids Entourage Effect

Plants produce several diverse organic compounds, most of which do participate directly in growth and development3. These substances are referred to as secondary metabolites. Flavonoids are categorized chemically as alkaloids, terpenoids, and phenolics. Flavonoids, terpenes, and cannabinoids of cannabis are able to work together to help regulate and protect the human body.

What are Flavonoids? Final Thoughts

Flavonoids have received much attention recently. Further studies are needed to clarify how flavonoids may be used to improve human health.3 Analytic techniques need improvement to allow better data collection on absorption and excretion of flavonoids and if there are long term effects of chronic flavonoid consumption.

Much research has emphasized the potential flavonoids have for improving various human health ailments, and new flavonoids have yet to be discovered in nature.3 There is a vast opportunity for these secondary metabolites to replace synthetic medicines with natural compounds that may be safer and even more effective, especially when paired with cannabinoids like CBD.

Currently, the intake of fruit, vegetables, and beverages containing flavonoids is generally recommended.3 It is essential to take caution, though, because no daily intake recommendation has been established. Ultimately, you should always consult your doctor for a personalized medical opinion before using any substance that has not been evaluated for safety, efficacy, or recommended dosage by the FDA.

References

  1. Bertoia ML, Rimm EB, Mukamal KJ, Hu FB, Willett WC, Cassidy A. Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124,086 US men and women followed for up to 24 years. BMJ. 2016;352:i17. Published 2016 Jan 28. doi:10.1136/bmj.i17 Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730111/
  2. ElSohly, M. A. (Ed.). (2007). Marijuana and the Cannabinoids. Springer Science & Business Media.
  3. Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016;5:e47. Published 2016 Dec 29. doi:10.1017/jns.2016.41 Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465813/
  4. McPartland, J. M., & Russo, E. B. (2001). Cannabis and cannabis extracts: greater than the sum of their parts?. Journal of Cannabis Therapeutics, 1(3-4), 103-132. Retrieved from: https://www.tandfonline.com/doi/abs/10.1300/J175v01n03_08