Luteolin is a flavonoid found in various plants, including cannabis, leaves, barks, and clover blossoms. It is a type of organic pigment called a carotenoid, related to beta-carotene and vitamin A. Many people consider luteolin "the eye vitamin." This article dives into the research studies on luteolin, explaining the clinical trials and examining animal research on how it works.
What is Luteolin?
Luteolin is a tetrahydroxyflavone, specifically a flavone (3′, 4′, 5, 7-tetra hydroxyl flavone) with a yellow crystalline appearance. Due to its color, the plant Reseda luteola, which contains luteolin, has been used as a source of dye since the first millennium B.C. This substance is widely distributed in the plant kingdom and has been studied extensively for its pharmacological properties, such as anti-inflammatory, antioxidant, and neuroprotective effects. Glycosides of luteolin have been identified in fossils of Ulmaceae species, dating back 36 to 25 million years.
As a natural herbal supplement, luteolin is readily available at health food stores and online. Normal dosages range from 100 mg to 500 mg in dried herb or liposomal forms, although most supplements and studies use dosages in the 100 mg range.
Food Sources of Luteolin
Luteolin is found in many foods, including egg yolks, spinach, kale, corn, orange pepper, kiwi fruit, grapes, zucchini, and squash. Other sources include mint, celery, broccoli, artichoke, and oranges. Common herbs such as parsley, thyme, rosemary, and oregano also contain luteolin. A cup of chamomile, peppermint, or dandelion tea provides a good source of luteolin. A spoonful of olive oil or a dash of oregano also offers rich sources.
The amount of luteolin varies; for example, one cup of cooked kale contains 44 mg, while a cup of cooked spinach has 26 mg, and a cup of broccoli contains 3 mg.
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Depending on the country, the daily intake of flavonoids in the human diet differs. The highest intake of flavonoids, including polymers, is in Ireland, with a daily intake of 851 mg/day, while the lowest daily intake for the same group is 225 mg in the Czech Republic.
Luteolin in Cannabis
The flavonoids in cannabis infuse the plant with bursts of flavor and color. Luteolin is a yellow crystalline substance that influences how your senses perceive what you see, taste, and smell in any given cannabis product. For example, luteolin could lend a yellowish hue to strains that are high in this flavonoid.
More importantly, the flavonoid luteolin infuses the cannabis plant with therapeutic potency. In conjunction with terpenes and cannabinoids, flavonoids create a synergistic entourage effect that optimizes any health benefits. As these plant compounds work together, they bind to receptors in your endocannabinoid system and/or other receptor systems, connecting with one another and sending messages to heal.
Uses and Effectiveness
Luteolin has shown potential in several areas, with varying degrees of scientific support.
Possibly Effective
- Age-Related Macular Degeneration (AMD): Taking lutein supplements by mouth for up to 36 months can improve some symptoms of AMD. More benefits might be seen when it's taken for at least 3 months at doses above 5 mg, and when it's combined with other carotenoid vitamins. However, lutein doesn't seem to prevent AMD from worsening over time.
- Cataracts: Eating higher amounts of lutein in the diet is linked with a lower risk of developing cataracts. However, it's not clear if taking lutein supplements by mouth helps people who already have cataracts.
Possibly Ineffective
- Bronchopulmonary Dysplasia: Giving preterm infants lutein and zeaxanthin by mouth doesn't reduce the chance of developing bronchopulmonary dysplasia.
- Necrotizing Enterocolitis (NEC): Giving preterm infants lutein and zeaxanthin by mouth doesn't prevent NEC.
- Retinitis Pigmentosa: Taking lutein by mouth doesn't improve vision or other symptoms in people with retinitis pigmentosa.
- Retinopathy of Prematurity: Giving preterm infants lutein and zeaxanthin by mouth doesn't prevent retinopathy of prematurity.
Other Potential Uses
Luteolin is being explored for numerous other purposes, but current evidence is insufficient to determine its effectiveness.
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Health Benefits and Uses
Research on the health benefits of luteolin is mostly limited to animal studies but is growing as scientists explore more about the therapeutic actions of dietary flavonoids. The current research on luteolin suggests that the flavonoid could have the following pharmacological uses:
Allergies
Luteolin extracted from peppermint leaves may inhibit histamines and therefore improve allergy symptoms. Histamines cause the skin to itch, and luteolin-rich peppermint oil may reduce the itching associated with allergies, including allergic asthma, as well as contact dermatitis, according to research published in the scientific journal Integrative Medicine. Other research suggests that luteolin could reduce allergic nasal inflammation. Luteolin can act as a mast cell stabilizer and reduce histamine release, which may benefit anyone dealing with mast cell activation syndrome (MCAS) or histamine intolerance.
Inflammation
The flavonoid luteolin may also be able to reduce non-allergic inflammation, including brain inflammation in multiple sclerosis (MS). Evidence published in the journal Nutrition and Lifestyle in Neurological Autoimmune Diseases suggests that luteolin could reduce inflammation related to MS. Related research has demonstrated that luteolin could play a role in reducing inflammation in the gut. Gastrointestinal inflammation is linked to many serious diseases, including Crohn’s disease and cancers of the GI tract.
Luteolin has shown important effects in the regulation of inflammation, in both in vitro and in vivo studies. The anti-inflammatory activities of luteolin were comprehensively reviewed in literature in two review papers. Authors described extensively the regulatory effects of luteolin on inflammatory mediators such as cytokines IL-6, IL-1β, TNF-α, enzyme COX-2 and prostaglandins PGEs.
Luteolin inhibits major inflammatory signaling pathways (e.g., NF-κΒ, JAK-STAT, NLRP3), leading consequently to reduced expression of pro-inflammatory mediators (e.g., TNF-α, IL-6, COX-2, iNOS, MMPs, IL1β, IL18). Moreover, luteolin seems able to activate the major antioxidant factor Nrf2, and increase the expression of antioxidant enzymes (e.g., SOD, CAT, GPx, GSH, HO-1).
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Based on its multi-targeted anti-inflammatory actions, luteolin appears to be a very promising natural agent for inhibiting abnormal inflammatory responses in chronic inflammatory conditions.
Cancer
Many types of cancer could benefit from luteolin. The flavonoid may be able to regulate estrogen levels, which could positively impact certain types of female cancers like breast cancer and ovarian cancer. Furthermore, luteolin could have an antioxidant effect on human lung cancer cells as well as work to inhibit the incidence of colon cancer.
Multiple studies have shown that luteolin induces apoptosis (cell death) in cancer cells in vitro. Studies show that luteolin inhibits cancer cell proliferation in two ways: by blocking the IGF1 receptor and by acting on GSK-3. A recent cell study on breast cancer showed that luteolin inhibited certain cancer-promoting genes.
While it is excellent that luteolin works to stop many different types of cancer cells from proliferating in a petri dish, the question remains whether this works at obtainable levels in real life. In other words, can you take enough supplemental luteolin to actually make a difference - without side effects?
Anxiety
Studies performed on animal models indicate that luteolin may help reduce anxiety. Along with decreased levels of anxiety, luteolin could promote better social interaction. However, these studies were conducted on mice and do not necessarily translate to human populations.
Cognitive Function and Neuroprotection
Research shows that luteolin may have clinically meaningful neuroprotective effects. Studies show that luteolin may help with cognitive dysfunction caused by inflammation. Luteolin could improve cognitive dysfunction by inhibiting neuroinflammation.
Other Potential Benefits
- Pain Management: Luteolin has shown a range of pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, and analgesic effects. It may be introduced as an adjuvant agent in established protocols for pain management, targeting the molecular pathways involved in the pathogenesis of chronic inflammatory and neuropathic pain.
- Protection Against Fatty Liver: Luteolin protects against fatty liver by improving intestinal barrier integrity.
- Uric Acid Reduction: Luteolin inhibits xanthine oxidoreductase, the enzyme needed for purine metabolism, which results in the formation of uric acid. Excess uric acid is linked to gout and gouty arthritis.
- Antiviral Activity: In trials for SARS-CoV-1, luteolin blocks viral entry into host cells. It also demonstrates antiviral activity against Japanese Encephalitis Virus and Influenza A Virus.
- Skin Protection: A clinical trial found that a nanoparticle formula containing a luteolin-rich plant extract decreased UVB-induced erythema (e.g., sunburns). The formula seemed to work when applied before UVB exposure and, to some extent, after exposure.
- Antimicrobial Properties: Luteolin demonstrates antimicrobial mechanisms against Staphylococcus Aureus and Listeria Monocytogenes and has antibiofilm properties.
Luteolin and Pain Management
Pain, along with redness, warmth, and swelling, are the characteristic symptoms of inflammation. Acute pain comes from the activation of nociceptors to noxious stimuli and works as a normal, warning system that protects the body from potential damage. Chronic pain, however, is a more complicated state and may involve nociceptive, neuropathic, or both components.
Luteolin has shown a range of pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, and analgesic effects. It may be introduced as an adjuvant agent in established protocols for pain management. Luteolin appears to be a very promising natural agent for inhibiting abnormal inflammatory responses in chronic inflammatory conditions.
Luteolin and Inflammatory Pain
Inflammation is an evolutionary conserved and protective reaction of the body against factors that threaten its normal functioning and homeostasis. Chronic conditions like osteoarthritis, rheumatoid arthritis, and inflammatory bowel disease are characterized by pathological and persistent pain. Luteolin has demonstrated important effects in regulating inflammation in both in vitro and in vivo studies. It regulates inflammatory mediators such as cytokines IL-6, IL-1β, TNF-α, enzyme COX-2, and prostaglandins PGEs.
Luteolin and Neuropathic Pain
Neuropathic pain results from damage or disease of the somatosensory nervous system and can be either peripheral or central in origin. Oxidative stress and nitrosative stress represent the loss of redox balance in the cells, due to high levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), respectively. Luteolin's antioxidant properties could contribute to the inhibition of chronic inflammation and neuropathic pain.
Side Effects and Precautions
Luteolin is generally safe to consume. Side effects may occur in some people, especially those who take the flavonoid in high doses as a dietary supplement, but these are rare and poorly understood.
When taken by mouth, consuming up to 20 mg of lutein daily as part of the diet or as a supplement appears to be safe. A specific product containing lutein 0.14 mg daily has been safely used in infants for 36 weeks.
In one mouse study, luteolin worsened chemical-induced colitis, but whether this applies to people remains to be seen. A cell line study suggests that luteolin (and quercetin) “display progesterone antagonist activity beneficial in a breast cancer model but deleterious in an endometrial cancer model.” However, this is just a cell line study, and it only suggests caution with consuming luteolin via supplement, not from a plant-rich diet.
One open-label pilot study on children with autism spectrum disorder (AUD) suggests that luteolin may have both positive and negative effects, as adaptive functioning improved, but their irritability increased as well.
Special Precautions and Warnings
- Pregnancy and Breast-feeding: Lutein is likely safe when used in the amounts found in food.
- Children: Lutein is likely safe when taken by mouth in appropriate amounts.
Interactions
Luteolin supplements may not be safe to take if you are taking blood pressure medications, calcium channel blockers, and certain other prescription drugs.
Dosage
Lutein is found in many foods, including egg yolks, spinach, kale, corn, orange pepper, kiwi fruit, grapes, zucchini, and squash. Lutein is also taken in supplements. It's most often been used by adults in doses of 10-20 mg by mouth daily, for up to 3 years. Many multivitamins contain lutein, usually providing a relatively small amount, such as 0.25 mg per tablet. Lutein is absorbed best when it's taken with a high-fat meal. Speak with a healthcare provider to find out what type of product or dose might be best for a specific condition.