Apigenin is Nature's most Powerful Flavonoid

Article by Stefan Burns - Updated May 2022. Join the Wild Free Organic email newsletter!

In the English Ballad Scarborough Fair, most well-known as sung by Simon and Garfunkel in their album Parsley, Sage, Rosemary, and Thyme, a man and women ask of each other impossible tasks so the other may demonstrate their true love, and sprinkled throughout the song is the refrain of “parsley, sage, rosemary, and thyme”.

To many curing cancer and other chronic inflammation-based diseases likewise seems an impossible task, but if the herbs of the ballad are sprinkled liberally throughout life then true healing is no longer out of reach thanks to the presence of a unique and very powerful anti-cancer phytochemical contained in all those herbs known as apigenin.

In this article we discuss the health benefits of apigenin, what foods to eat to receive more apigenin into the diet, and other high-density ways of supplementing apigenin so you can enjoy all the amazing health benefits of this unique flavonoid phytochemical.

Curly parsley from my 2021 summer garden, zone 7a. Yum!

Pharmacology of Apigenin

Apigenin is a phytochemical flavonoid (more specifically a flavone) naturally produced by plants shown to exhibit several biologic activities such as being an antioxidant, anti-inflammatory, antimicrobial, anti-cancer, neuroprotective, and cardioprotective.

Apigenin is synthesized in a number of plants as secondary metabolite via the shikimate pathway* (how all flavonoids are synthesized). Once apigenin has been produced by a plant it’s bound to sugar molecules in various ways creating what are known as glycosides which are another class of powerful health-promoting phytochemicals. Flavonoids like apigenin are produced by plants for functions like protection against ultraviolet light, defense against insects, fungi, and microorganisms, as antioxidants, and as plant hormone controllers. Just as plants use flavonoids to improve their lot in life, so too can we, with flavonoids like apigenin and quercetin (among many others) raising the efficiency and stable functioning of biologic systems.

Note* - The reason pesticides like glyphosate are so effective at killing bacteria, fungi, and plants is because they turn off the shikimate pathway. Non-organic produce having been grown with disrupted shikimate metabolism will therefore contain much less of the valuable phytochemicals that our bodies crave! Something to consider next time you’re purchasing vegetables and are wondering whether to buy conventional (sprayed with glyphosate) or organic (not sprayed with glyphosate) fruits and vegetables.

Apigenin Bioavailability

Apigenin glycosides are more bioavailable than free apigenin as free apigenin has very poor water solubility.

In the intestines, apigenin is extensively metabolized into forms more readily transported to the liver before being distributed out to tissues of the body. Any apigenin that makes it past the small intestine transits to the colon where it also has biologic effects before eventually being eliminated from the body. Remaining apigenin from the tissues (and some from the liver) are eventually processed by the kidneys and excreted via urine.

From the whole-food source of parsley (the densest source of apigenin known), the excretion half-life for apigenin was observed to be about 12 hours. There exist significant individual variation in the bioavailability and excretion of apigenin, but in general apigenin is absorbed slowly by the body and eliminated slowly by the body (important to discuss further, see side effects section below). No difference in the mean excretion of apigenin has been observed between men and women.

If apigenin is taken in reasonable amounts the long half-life of apigenin proves to be one of its main benefits as a wellness promoting phytochemical. The longer a chemical can stay in the body, the more time it has to exert biologically-relevant effects, and by eating a diet high in apigenin, over time the body builds up consistent levels of apigenin in the bloodstream that keep inflammation low, among many other health improvements.

Apigenin Benefits and Uses

If you’ve read through the herb section of Wild Free Organic, you’ll have found that the theme of many health-promoting herbs is that they are always possess antioxidant, anti-inflammatory, and antimicrobial properties. Antioxidants help neutralize free radicals in the body which otherwise would cause oxidative stress and DNA damage. Inflammation isn’t bad per-say as it is vitally important in the healing process, but the out-of-balance modern lifestyle has inflammation elevated way beyond normal levels chronically for many people. And the natural antimicrobial properties of herbs keep the gut’s microbiome healthy and in-check while also sweeping the bloodstream clear of pathogens which increases immunity.

When antioxidant, anti-inflammatory, and anti-microbial properties are combined together thanks to flavonoids like apigenin, and biologically relevant amounts are consumed consistently, beneficial actions at the cellular scale are felt at the human scale for example as reductions in cancer, improved sleep and less anxiety, better gut health, and optimized hormone levels for men and women. Apigenin is most popularly known for its anti-cancer, anti-mutagenic, and chemoprotective effects so we’ll start there when discussing the health benefits of apigenin.

Apigenin for Cancer

In most situations when a cell undergoes a genotoxic mutation DNA repair mechanisms kick in and repair the damage or the cell undergoes apoptosis (programmed cell death) and is terminated. If the DNA damage isn’t fixed and the cell doesn’t undergo apoptosis then the mutated cell begins to deviate from its normal behaviors and becomes cancerous.

Apigenin plays an important role in cancer prevention by inducing apoptosis and inhibiting cell proliferation in mutated cells. Apigenin triggers various anti-cancer pathways and activates tumor suppressive genes. Apigenin also further combats the rise and spread of cancer through its binding action to certain proteins and also in how it adjusts certain cellular receptors in their expression and density. Apigenin bolsters all of these anti-cancer effects but also inhibiting excessive platelet adhesion thereby improving the transport of oxygen, nutrients, and immune cells throughout the body.

One special trait of apigenin is that it is able to overcome the multi-drug resistance some tumor cells have by inhibiting the viability of the mutated cells while increasing their cellular uptake of doxorubicin (a chemotherapy medication).

Apigenin is one of the most powerful anti-cancer phytochemicals currently known and for anyone who has cancer reading this I would suggest you read the full research paper linked as the sixth reference for this article (see end).

Apigenin for Sleep

Apigenin binds to benzodiazepine receptors in the brain which, if taken in high enough doses, can trigger muscle relaxation and sedation.

Chamomile is a common source of apigenin, and chamomile is well-known for it’s relaxation and sleep benefits, which can be partly ascribed to apigenin’s neurochemical interactions. Not only does chamomile activate the "rest and digest” parasympathetic nervous system, it also improves day-time functioning because 8-12 Hz alpha brainwaves are increased in power. Alpha brainwaves are the gateway between wakefulness and sleep, and strong alpha brainwave activity in general is correlated with higher levels of consciousness.

Apigenin for Anxiety and Depression

Anxiety, depression, insomnia, and other mental health issues are central nervous system (CNS) related disorders, and apigenin’s influence over the CNS is beneficial in reducing these mental health issues. There is increasing awareness surrounding the effectiveness of phytochemicals like apigenin or sulforaphane in treating mental health issues, and an important thing to know then if seeking to use natural alternatives for mental health treatment is the effectiveness of a bioactive compound is determined in part by its ability to pass through the blood-brain barrier. Of the many flavonoids that exist, apigenin is near the top of the list in its ease of penetration of the blood brain barrier.

Apigenin reduces anxiety, depression, and other central nervous system disorders through a few different factors. Apigenin upregulates the production of brain-derived neurotropic factor, an important protein for nerve cell growth and survival. Apigenin lowers stress-induced alterations in the brain and it reverses mild stress-induced increases in corticosteroid hormones. Apigenin possibly has a role in modulating the neurotransmission activity of noradrenalin, dopamine, and serotonin, and by doing this apigenin helps to prevent abnormal behavior.

The beneficial neuroprotective effects of apigenin listed in the next section are also applicable to this section.

Apigenin is Neuroprotective

As a neuroprotective agent, apigenin reduces oxidative damage, neural inflammation, and activation of the central nervous system’s immune microglial cells. Apigenin has been shown to cause a reduction in amyloid deposits in the brain and it has an ameliorating effect on Alzheimer’s disease. Apigenin causes improvements in memory, most notably spatial learning and memory.

Possibly one of apigenin’s most important effects is that is has a neurovascular protective effect, helping to keep the brain well supplied with oxygen and nutrient-rich blood. Not only does apigenin have an easy time passing through the blood-brain barrier, its presence also maintains the healthy status of the brain’s vascular network, which is a win-win.

Apigenin for Gut Health

Not all flavonoids will be absorbed in the small intestine, and any flavonoids (like apigenin) that reach the colon beneficially interact with the microbiome there. Flavonoids and their metabolites alter the microbiome by inhibiting the growth of various pathogens while increasing the beneficial genera such as Bifidobacterium and Lactobacillus. Through these actions gut health is improved because endotoxin production is reduced, the conversion of primary into secondary bile acids is increased, and overall nutrient absorption increases. Flavonoids are one of the best things to ensure you’re getting adequate amounts of in your diet if looking to heal gastrointestinal issues or maintain good gut health. Flavonoids improve intestinal barrier function by strengthening epithelial tight-junctions which has a big impact on reducing gut inflammation.

If you are experiencing gut health problems then the Holistic Gut Health Guide is the all-in-one-guide you need to begin healing your digestive system and microbiome.

Apigenin for Women

As women age hormone levels decline, notably progesterone which affects the functioning of various neurotransmitters like GABA. Women with lower progesterone levels at any age have a greater likelihood of experiencing depression, anxiety, irritability, and insomnia. Headaches, migraines, and mood changes are more common, as is irregularity in the menstrual cycle. Apigenin has some effect in improving progesterone levels and thus can help mitigate the effects of low progesterone levels in women of all ages.

Apigenin for Men

The two main ways apigenin specifically helps men is in regards to their hormonal and prostate health.

Apigenin and Testosterone

Apigenin broadly improves the function of Leydig cells, the cells responsible for testosterone production in the testes. Apigenin also reduces heat-induced damage to the extremely heat sensitive Leydig cells. Apigenin enhances steroidogenesis by increasing the sensitivity of Leydig cells to cAMP stimulation.

In addition to improving steroidogenesis, apigenin can promote skeletal muscle hypertrophy and myogenic differentiation of muscle cells through its actions as a potent aromatase inhibitor (like most plant flavonoids). Aromatase is an enzyme that converts androgens like testosterone into estrogenic hormones like estradiol, and by inhibiting the action of aromatase enzymes throughout the body more androgenic hormone levels can be maintained.

Apigenin for Prostate Health

Plant flavonoids like apigenin induce apoptosis in prostate carcinoma (epithelial cancer) cells by inhibiting fatty acid synthase, a long chain fatty-acid synthesis enzyme that is over-expressed in prostate cancer cells. Apigenin also changes various cellular pathways the inhibits the growth of prostate cancer. One of these pathways is the uptake and accumulation of apigenin in the nuclear matrix of a cell, binding apigenin to DNA which reduces oxidative DNA damage and apoptosis in healthy prostate epithelial cells.

One of the main concerns regarding any chemotherapy treatment is how it also damages and kills healthy cells alongside mutated ones. By protecting healthy cells and by fighting cancer in its own way apigenin is truly a miracle flavonoid that is easily and safely added alongside existing cancer treatment options.

What is Apigenin Found In?

As a plant-created flavonoid apigenin is found in a variety of herbs, fruits, and vegetables. Most commonly apigenin isn’t found in its free form but bound as one of its various glycosides. For example apigenin does not occur in living chamomile flowers, instead residing in the plant as apigenin 7-glycoside and its derivatives. Once harvested some of the apigenin glycosides convert into free apigenin.

Whether an apigenin containing food is eaten fresh or dried (a denser source), the apigenin will be absorbable.

Herbs High in Apigenin

Parsley is the richest known source of apigenin and there is nothing else that comes close. Fresh parsley contains ~2.2 mg of apigenin per gram of fresh parsley. With its water content removed dried parsley is an even denser source of apigenin coming in at ~45 mg/g.

Chamomile (Matricaria recutita) is another source of apigenin that’s well-known, with dried chamomile flower containing 3-5 mg/g.

Peppermint contains 0.055 mg of apigenin per gram of fresh leaves, and the apigenin density is higher in dried peppermint.

Thyme contains ~0.025 mg of apigenin per gram of fresh leaves, and dried thyme has a higher apigenin density.

Oregano contains ~0.025 mg of apigenin per gram of fresh leaves, and dried oregano is an even denser source of apigenin.

Sage, rosemary, and tea leaves are other sources of apigenin. Lastly one important thing to note regarding the apigenin content of herbs, and this also applies more broadly to all polyphenols found in herbs, is that there typically is a significant increase in total polyphenols from April to September, so the apigenin content of food does vary with the seasons.

Fruits and Vegetables High in Apigenin

Since apigenin is a common flavonoid it’s found in some concentration in most fruits and vegetables.

Celery is a vegetable known for its high apigenin content, and all parts of the celery plant contain apigenin in different ratios. Celery seed has the densest concentration of apigenin at 0.8 mg/g, whereas celery hearts have a lower density of 0.02 mg/g, and celery stalk is even lower still at only 0.003 mg/g.

Other fruits and vegetables known for their apigenin content are rutabaga, green chili peppers, onions, and oranges.

Liposomal Apigenin

The health benefits of apigenin are becoming more well-known in the medical field and it’s common to be recommended liposomal apigenin for a variety of health reasons. A liposome is a spherical drug delivery vehicle made of a lipid bi-layer that increases bioavailability of the nutrient encapsulated within it into the bloodstream. Apigenin is already very bioavailable and liposomal apigenin is only really useful in the context of shuttling the majority of the apigenin into the bloodstream, whereas normally the tissues of the digestive system will absorb and use some apigenin themselves, some apigenin will make it into the bloodstream, and some apigenin will also make its way to the microbiome of the large intestine.

There are benefits to letting apigenin naturally be distributed throughout the body, specifically having apigenin make it to the microbiome is very valuable for the gut-brain axis, metabolic health, and the cardiovascular system. The microbiome produces biologically useful secondary metabolites from flavonoids like apigenin, and for this reason supplementing with a natural source of apigenin like dried parsley is preferred.

Apigenin Side Effects

There is some concern that exist regarding apigenin and its potential to build up in the body based on its half-life in rats, which is 92 hours. The half life of apigenin in humans though is 12 hours, and there is little evidence to suggest that apigenin builds up to dangerous levels or promotes adverse metabolic reactions when consumed as part of a normal diet.

Direct supplementation of high doses of isolated apigenin can result in liver toxicity over time, and its for this reason that I believe its best that those who wish to supplement with apigenin capsules don’t supplement with them daily and instead follow a more holistic approach, sticking with whole foods and herbal teas. Information for those interested in supplementing with high doses of apigenin and for others who want to follow the holistic approach is below.

Supplement Apigenin

There are two main methods to follow when supplementing with any compound or chemical. The first method is to supplement with the desired chemical just 1-3x at a high dose for an acute effect. The second method is to incorporate into the diet natural sources of the desired chemical for much broader long term health benefits. With good understanding of what a chemical does and its safety profile methods 1 and 2 can be combined. We’ll start with the low-dose daily way to add apigenin into the diet and then progress upwards towards the most potent forms available.

Chamomile, Dandelion, Peppermint Tea for Apigenin

An excellent way to add extra apigenin to the diet is to drink a 1:1:1 chamomile, dandelion, and peppermint herbal tea. This herbal tea blend is so powerfully healthy for you because of the presence of flavonoids like apigenin, quercetin, and hundreds of other health-promoting phytochemicals.

All three of these herbs are powerful antioxidants, anti-inflammatories, and natural antimicrobials. Drinking this tea will boost your immune system and help you get over a cold/flu/covid faster, will reduce symptoms associated with inflammation-based and autoimmune diseases, and is excellent for healing the digestive system and keeping it functioning at a high level. I’ve writen more about the benefits of drinking herbal teas for improving gut health and for use during fasting, and if you’re currently facing gut health problems I highly encourage you to learn more.

Drinking herbal teas is one of the best preventative health strategies that exists. Each cup is packed with biologically useful phytonutrients that the body craves, and with so many different herbs that exist it never gets boring. Drink a cup or two of chamomile/dandelion/peppermint tea a day and with the 12 hour half life of apigenin it’s not an issue if a few days are missed every now and then. All three of these herbs are extremely safe with no known toxicity concerns.

Mountain Rose herbs sells organic dandelion root, chamomile flowers, and dried peppermint leaves.

Dried parsley for Apigenin

Dried parsley is a ridiculously dense source of apigenin coming in at ~45 mg/g. While pure apigenin supplements do exist as you’ll see below, dried parsley is the best way to supplement with high amounts of apigenin because in addition to receiving the apigenin you also receive all the other useful vitamins, nutrients, and phytochemicals that parsley has to offer. Parsley is a dense source of vitamin C, vitamin A, vitamin K, calcium, and iron. All of the components that make up parsley aid in the bioavailability and health effects of the other components in what’s known as the entourage effect. So when using dried parsley to intake higher levels of apigenin (for example to aid in the fight against cancer), you not only receive abundant apigenin but lots of other health promoting goodies that would not come when supplementing with apigenin in a standardized pill form.

You can purchase dried parsley in the spice section at the local supermarket or save some money by buying dried parsley online. You can purchase dried parsley on amazon, where it’s usually sold in greater quantities and cheaper in price than the supermarket, or from my favorite supplier of herbs, essential oils, and other health and wellness products Mountain Rose Herbs who also sells organic dried parsley leaf.

Easy ways to incorporate dried parsley into your diet is to mix it into different spreads like cream cheese and hummus, to sprinkle it liberally on top of meals like a grain bowl, mix it into soup or paste-type dishes, you get the idea.

Pure Apigenin Supplements

Highly standardized apigenin supplements can be useful under certain circumstances. For example if someone is having severe gut health issues and even dried parsley is likely to cause too much gastrointestinal upset, then a pure apigenin supplement can be useful combined alongside herbal teas. Nootropics Depot sells a few different supplements that contain apigenin, most notably they sell a raw 98% apigenin powder that’s also available as 98% apigenin capsules.

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Try Herbalism

A final message to leave you with is to never underestimate the healing power of natural remedies, a great introduction being herbal teas. A lot of supplements are very expensive and have poor safety and quality testing. For the same price or less as a few different health supplements an entire assortment of health-promoting herbs can be acquired through a supplier like Mountain Rose Herbs. Try natural herbal remedies at least once and see if they can help you. A good place to start learning more about herbs is on the herbs section of this website.

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References:

1. Ali F, Rahul, Naz F, Jyoti S, Siddique YH. Health functionality of apigenin: A review. International Journal of Food Properties. 2017;20(6):1197-1238.

2. Nielsen SE, Young JF, Daneshvar B, et al. Effect of parsley (petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects. Br J Nutr. 1999;81(6):447-455.

3. Salehi B, Venditti A, Sharifi-Rad M, et al. The therapeutic potential of apigenin. IJMS. 2019;20(6):1305.

4. Pei R, Liu X, Bolling B. Flavonoids and gut health. Current Opinion in Biotechnology. 2020;61:153-159.

5. Higdon J. Flavonoids. Micronutrient Information Center, Linus Pauling Institute, Oregon State University. https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids

6. Shankar E, Goel A, Gupta K, Gupta S. Plant flavone apigenin: an emerging anticancer agent. Curr Pharmacol Rep. 2017;3(6):423-446.

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