Hydroxytyrosol

• Potent antioxidant activity
• Cardiovascular protection
• Anti-inflammatory effects
• Neuroprotective properties

• Antimicrobial activity
• Bone health support
• Metabolic health improvement
• Skin protection
• Cancer preventive potential

Hydroxytyrosol (HT) is a phenolic compound with a catechol structure that exerts its biological effects through multiple mechanisms. Its primary mechanism of action is as a potent antioxidant, with an oxygen radical absorbance capacity (ORAC) value significantly higher than other well-known antioxidants such as vitamin C, vitamin E, and resveratrol. The catechol structure of hydroxytyrosol, with its two adjacent hydroxyl groups on the aromatic ring, enables it to efficiently scavenge free radicals and reactive oxygen species (ROS) by donating hydrogen atoms. This structure also allows hydroxytyrosol to chelate metal ions such as iron and copper, which can catalyze oxidative reactions, thereby providing additional antioxidant protection.

Beyond direct free radical scavenging, hydroxytyrosol activates endogenous antioxidant defense systems by upregulating the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase. This occurs primarily through activation of the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, a master regulator of cellular antioxidant responses. Hydroxytyrosol binds to Keap1, releasing Nrf2, which then translocates to the nucleus and binds to Antioxidant Response Elements (AREs) in the promoter regions of antioxidant genes. Hydroxytyrosol exhibits potent anti-inflammatory effects through multiple pathways.

It inhibits the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6) in various cell types. It also suppresses the activity of inflammatory enzymes including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), thereby reducing the production of prostaglandins and nitric oxide. A key mechanism underlying hydroxytyrosol’s anti-inflammatory effects is its inhibition of nuclear factor-kappa B (NF-κB) activation. By preventing the phosphorylation and degradation of IκB (the inhibitor of NF-κB), hydroxytyrosol keeps NF-κB sequestered in the cytoplasm, preventing its translocation to the nucleus and subsequent activation of pro-inflammatory genes.

In cardiovascular health, hydroxytyrosol protects against atherosclerosis through multiple mechanisms. It inhibits the oxidation of low-density lipoprotein (LDL) cholesterol, a critical step in atherosclerotic plaque formation. It also improves endothelial function by enhancing nitric oxide (NO) production through increased expression and activity of endothelial nitric oxide synthase (eNOS). Additionally, hydroxytyrosol inhibits platelet aggregation and reduces the expression of adhesion molecules such as VCAM-1 and ICAM-1 on endothelial cells, thereby reducing leukocyte adhesion and infiltration into the arterial wall.

Hydroxytyrosol demonstrates neuroprotective effects by reducing oxidative stress and inflammation in neural tissues. It protects neurons from apoptosis induced by oxidative stress and excitotoxicity. Studies suggest it may enhance mitochondrial function and biogenesis in neuronal cells, potentially contributing to its neuroprotective effects. In metabolic health, hydroxytyrosol improves insulin sensitivity by enhancing insulin signaling pathways and glucose uptake in skeletal muscle and adipose tissue.

It activates AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, which promotes fatty acid oxidation and glucose uptake while inhibiting lipogenesis. Hydroxytyrosol also exhibits antimicrobial properties against various bacteria, fungi, and viruses. It disrupts bacterial cell membranes and inhibits bacterial adhesion to host cells. Against viruses, it may interfere with viral attachment and entry into host cells.

In cancer prevention, hydroxytyrosol induces cell cycle arrest and apoptosis in various cancer cell lines. It inhibits critical enzymes involved in cancer progression, such as matrix metalloproteinases (MMPs), which facilitate tumor invasion and metastasis. Hydroxytyrosol also inhibits angiogenesis by reducing the expression of vascular endothelial growth factor (VEGF) and other angiogenic factors. At the epigenetic level, hydroxytyrosol modulates microRNA expression and DNA methylation patterns, potentially influencing gene expression related to inflammation, oxidative stress, and cell proliferation.

These multiple mechanisms of action work synergistically to confer the diverse health benefits associated with hydroxytyrosol consumption.

The optimal dosage of hydroxytyrosol has not been definitively established through comprehensive clinical trials. However, based on existing research and the European Food Safety Authority (EFSA) health claim, a daily intake of at least 5 mg of hydroxytyrosol and its derivatives (such as oleuropein complex) is recommended for cardiovascular benefits, specifically for the protection of LDL particles from oxidative damage. Most clinical studies have used doses ranging from 5-25 mg of hydroxytyrosol per day, with positive effects observed across this range. For general antioxidant support and health maintenance, a daily dose of 5-10 mg of hydroxytyrosol appears to be sufficient.

For specific therapeutic purposes, higher doses of 15-25 mg per day may be more appropriate, though these should be taken under healthcare provider guidance. It’s important to note that hydroxytyrosol can be consumed either as a supplement or through dietary sources such as extra virgin olive oil (EVOO). Approximately 50 ml (about 3.5 tablespoons) of high-quality EVOO may provide around 5 mg of hydroxytyrosol and its derivatives, though this varies significantly depending on the olive variety, processing methods, and storage conditions.

Hydroxytyrosol demonstrates relatively high bioavailability compared to many other polyphenols, with absorption rates estimated between 40-95% of the ingested dose, depending on the formulation and delivery method. When consumed in its free form, hydroxytyrosol is primarily absorbed in the small intestine through passive diffusion due to its relatively small molecular weight (154.16 g/mol) and moderate hydrophilicity. The absorption process begins rapidly, with hydroxytyrosol detectable in plasma within 15-30 minutes after oral administration. Peak plasma concentrations typically occur between 30 minutes and 2 hours post-ingestion, indicating rapid absorption kinetics.

When consumed as part of olive oil or as oleuropein (a hydroxytyrosol precursor), the absorption may be slower but still substantial, as oleuropein undergoes hydrolysis in the gastrointestinal tract to release hydroxytyrosol. After absorption, hydroxytyrosol undergoes extensive first-pass metabolism in the intestinal epithelium and liver, where it is primarily conjugated through phase II metabolic reactions, including glucuronidation, sulfation, and methylation. These conjugated forms (particularly hydroxytyrosol-3-O-glucuronide, hydroxytyrosol-4-O-glucuronide, and hydroxytyrosol-3-O-sulfate) represent the majority of circulating hydroxytyrosol metabolites in plasma. Despite this extensive metabolism, evidence suggests that these conjugated forms retain significant biological activity, particularly antioxidant capacity.

The plasma elimination half-life of hydroxytyrosol and its metabolites is relatively short, approximately 2-3 hours, indicating rapid clearance from the bloodstream. However, tissue distribution studies in animals suggest that hydroxytyrosol can accumulate in various tissues, including the liver, kidney, muscle, and brain, potentially extending its biological effects beyond its plasma half-life. Excretion occurs primarily through the urine, with approximately 30-60% of the ingested dose recovered in urine within 24 hours, mainly as conjugated metabolites. A smaller portion is excreted via the biliary route into feces.

Consumption with dietary fats (such as in olive oil) enhances hydroxytyrosol absorption by promoting the formation of mixed micelles and stimulating bile secretion, Phospholipid complexation significantly improves bioavailability by enhancing membrane permeability and providing protection from first-pass metabolism, Microencapsulation techniques protect hydroxytyrosol from degradation in the gastrointestinal environment and can provide controlled release, Liposomal formulations enhance cellular uptake and improve systemic bioavailability, Cyclodextrin complexation increases aqueous solubility while protecting hydroxytyrosol from oxidation, Nanoemulsion delivery systems improve dissolution rate and enhance intestinal permeability, Co-administration with piperine (black pepper extract) may inhibit glucuronidation and increase bioavailability, Consuming hydroxytyrosol with vitamin C may enhance its stability and reduce oxidation before absorption, Solid lipid nanoparticles provide controlled release and improved bioavailability, Consuming hydroxytyrosol with a meal rather than on an empty stomach may enhance absorption through longer gastrointestinal transit time and increased bile secretion

For optimal absorption and effectiveness, hydroxytyrosol supplementation should follow specific timing considerations. Taking hydroxytyrosol with meals, particularly those containing some fat, significantly enhances absorption by stimulating bile release and promoting micelle formation. Morning administration is often recommended to align with the body’s natural circadian rhythms and to potentially provide antioxidant protection throughout the day. However, for cardiovascular benefits, some research suggests that evening administration may be more effective, as certain cardiovascular risk factors (such as LDL oxidation and inflammatory processes) may be more pronounced during nighttime hours.

For metabolic health, taking hydroxytyrosol approximately 15-30 minutes before meals may help optimize its effects on glucose metabolism and insulin sensitivity. Given hydroxytyrosol’s relatively short half-life (2-3 hours), dividing the daily dose into two administrations (morning and evening) may provide more consistent plasma levels and extended benefits. For those using hydroxytyrosol primarily for its antioxidant properties, taking it before exposure to oxidative stressors (such as intense exercise, air travel, or significant sun exposure) may provide timely protection. When using hydroxytyrosol topically for skin health, application after cleansing and before heavier creams or oils allows for better penetration.

For maximum benefit, consistency in daily administration is more important than precise timing, as some of hydroxytyrosol’s effects may be cumulative and require regular exposure over time. If taking multiple supplements, be aware that hydroxytyrosol is generally well-tolerated and has few known interactions, but separating it from iron supplements by at least 2 hours may prevent potential interference with iron absorption due to hydroxytyrosol’s metal-chelating properties.

• Mild gastrointestinal discomfort (rare)
• Temporary changes in taste perception (rare)
• Mild headache (very rare)
• Allergic reactions in individuals with olive allergies (rare)
• Potential hypotensive effect when taken in very high doses (rare)

• Known allergy or hypersensitivity to olives or olive products
• Caution advised in individuals with low blood pressure, as high doses of hydroxytyrosol may have hypotensive effects
• Caution advised in individuals with bleeding disorders or those taking anticoagulant medications, due to potential mild antiplatelet effects
• Pregnancy and lactation (due to insufficient safety data, though dietary consumption through olive oil is considered safe)
• Scheduled surgery (discontinue at least 2 weeks before due to theoretical anticoagulant effects)

• Anticoagulant and antiplatelet medications (theoretical risk of enhanced effect due to hydroxytyrosol’s mild antiplatelet properties)
• Antihypertensive medications (potential additive effect, particularly with high doses of hydroxytyrosol)
• Iron supplements (hydroxytyrosol may reduce iron absorption if taken simultaneously due to its metal-chelating properties)
• Diabetes medications (theoretical risk of enhanced hypoglycemic effect, though clinical significance is unclear)
• Cholesterol-lowering medications (potential synergistic effect, generally beneficial but may require monitoring)

Hydroxytyrosol has demonstrated an excellent safety profile in both animal and human studies. The European Food Safety Authority (EFSA) has evaluated hydroxytyrosol and concluded that it is safe for human consumption at the doses typically used in supplements (5-25 mg per day). Toxicological studies in animals have established a No Observed Adverse Effect Level (NOAEL) of 500 mg/kg body weight per day, which translates to approximately 35 grams per day for a 70 kg adult when applying a standard safety factor of 100. This is far above any dose used in supplements or achievable through dietary consumption.

In human studies, doses up to 100 mg per day have been used for periods of 3-6 months without significant adverse effects. Based on the available evidence, a conservative upper limit for long-term daily consumption would be approximately 50-100 mg of hydroxytyrosol per day for most healthy adults. However, most supplements provide 5-25 mg per day, well below this theoretical upper limit. For context, consuming 50 ml (about 3.5 tablespoons) of high-quality extra virgin olive oil provides approximately 5 mg of hydroxytyrosol and its derivatives, depending on the specific oil.

It’s worth noting that individuals with specific health conditions, particularly those with low blood pressure or bleeding disorders, should exercise caution with higher doses and consult healthcare providers. Pregnant and lactating women should limit intake to dietary sources (olive oil) rather than supplements due to limited safety data in these populations. As with any supplement, it’s advisable to start with lower doses and gradually increase if needed, monitoring for any adverse effects.

In the United States, hydroxytyrosol is regulated as a dietary ingredient under the Dietary Supplement Health and Education Act (DSHEA) of 1994. It has not been approved as a drug or food additive by the FDA. Hydroxytyrosol has Generally Recognized as Safe (GRAS) status when used in accordance with good manufacturing practices. This status applies to hydroxytyrosol derived from olive oil and olive extracts, as these sources have a long history of safe consumption.

Synthetic hydroxytyrosol may require additional regulatory review depending on the specific manufacturing process. As with all dietary supplements, manufacturers of hydroxytyrosol products must ensure their products are safe and properly labeled. They cannot make claims about treating, curing, or preventing specific diseases, though structure/function claims (such as ‘supports cardiovascular health’ or ‘provides antioxidant protection’) are permitted with appropriate disclaimers. The FDA has not established a specific recommended daily intake or upper limit for hydroxytyrosol.

The FDA has not approved any qualified health claims for hydroxytyrosol, unlike the European regulatory authorities.

Eu: In the European Union, hydroxytyrosol has received significant regulatory recognition. In 2011, the European Food Safety Authority (EFSA) approved a health claim for olive oil polyphenols, stating that 5 mg of hydroxytyrosol and its derivatives (oleuropein complex and tyrosol) daily contributes to the protection of blood lipids from oxidative damage. This is one of the few approved health claims for polyphenols in Europe. In 2017, EFSA issued a positive opinion on the safety of hydroxytyrosol as a novel food ingredient under Regulation (EU) 2015/2283. This assessment concluded that hydroxytyrosol is safe for use in fish and vegetable oils up to specific concentrations and as a food supplement with a recommended daily intake of up to 20 mg. Synthetic hydroxytyrosol has also been assessed and approved as safe, provided it meets specific purity criteria. The EU has not established a specific upper limit for hydroxytyrosol consumption, though the novel food approval specifies maximum use levels in various applications.

Japan: In Japan, hydroxytyrosol may be used in Foods with Function Claims (FFC) if scientific evidence supports its benefits. Manufacturers must notify the Consumer Affairs Agency before marketing such products. Hydroxytyrosol is not specifically listed as a designated food additive by the Ministry of Health, Labour and Welfare, but it may be used as a component of olive extracts, which are permitted. The Japanese regulatory framework does not have specific provisions for hydroxytyrosol as an isolated compound, but products containing it may be marketed as foods or food supplements.

Canada: Health Canada regulates hydroxytyrosol as a natural health product (NHP) ingredient. It is listed in the Natural Health Products Ingredients Database with a proper name of ‘Olive extract’ when derived from Olea europaea. Products containing hydroxytyrosol must obtain a Natural Product Number (NPN) before being marketed in Canada. Health Canada has not approved specific health claims for hydroxytyrosol, though general claims related to antioxidant activity may be permitted with appropriate evidence. As with most jurisdictions, there is no established upper limit for hydroxytyrosol intake in Canada.

Australia: The Therapeutic Goods Administration (TGA) in Australia regulates hydroxytyrosol-containing products as listed complementary medicines. Such products must be listed on the Australian Register of Therapeutic Goods (ARTG) before they can be marketed. Hydroxytyrosol derived from olive sources is generally considered safe based on the traditional use of olive products. The TGA has not approved specific health claims for hydroxytyrosol, though general claims related to antioxidant activity may be permitted with appropriate evidence. Australia has not established a specific upper limit for hydroxytyrosol consumption.

Medium to High

The cost of hydroxytyrosol supplements varies significantly based on several factors, including purity, source (natural vs. synthetic), formulation, and brand reputation. Typical retail prices for hydroxytyrosol supplements range from $0.50 to $3.00 per day for an effective dose (5-15 mg of hydroxytyrosol). Lower-cost options ($0.50-$1.00 per day) typically include olive leaf extracts or olive fruit extracts standardized to contain hydroxytyrosol, though the exact content may vary and often includes other olive polyphenols.

Mid-range products ($1.00-$2.00 per day) usually offer more precisely standardized hydroxytyrosol content, often derived from olive oil byproducts or through semi-synthetic processes. Premium products ($2.00-$3.00+ per day) typically feature high-purity hydroxytyrosol (95%+), enhanced delivery systems (such as liposomal or phospholipid complexes), or specialized formulations combining hydroxytyrosol with synergistic compounds. An alternative source of hydroxytyrosol is high-quality extra virgin olive oil, which typically contains 1-5 mg of hydroxytyrosol and its derivatives per 50 ml (about 3.5 tablespoons). Premium olive oils with verified high polyphenol content cost approximately $15-30 per 500 ml bottle, translating to roughly $1.50-3.00 per effective dose (50 ml containing 5 mg of hydroxytyrosol and derivatives).

While this may seem comparable to supplements, olive oil provides additional nutritional benefits from its fatty acid profile and other bioactive compounds.

The value proposition of hydroxytyrosol varies depending on the specific health goals and source considerations. For cardiovascular health, hydroxytyrosol offers good value compared to many other supplements. The EFSA-approved health claim for protection of LDL from oxidative damage is supported by multiple clinical studies, providing a relatively high level of evidence for its efficacy at doses of 5-10 mg daily. At $0.50-2.00 per day for this dose, hydroxytyrosol compares favorably to other cardiovascular supplements like CoQ10 or certain omega-3 formulations.

For general antioxidant support, hydroxytyrosol is one of the most potent natural antioxidants available, with an ORAC value significantly higher than vitamin C, vitamin E, or resveratrol. This high potency may justify its higher cost compared to more common antioxidants. When comparing different sources, high-polyphenol olive oil may offer the best overall value, as it provides hydroxytyrosol along with other beneficial compounds and can be used as a food ingredient, effectively serving dual purposes. However, for those seeking precise dosing or who don’t regularly consume olive oil, supplements may be more practical.

Among supplement forms, olive leaf extracts typically offer the lowest cost per mg of hydroxytyrosol but may have more variable bioavailability. Purified hydroxytyrosol products cost more but provide more consistent dosing and potentially better absorption. Advanced delivery systems (liposomal, phospholipid complexes) command premium prices but may offer enhanced bioavailability, potentially providing better value despite higher costs. For specific therapeutic applications requiring higher doses (15-25 mg daily), the cost increases proportionally, potentially reducing cost-efficiency unless targeting conditions with strong supporting evidence.

The long-term value of hydroxytyrosol supplementation may improve as manufacturing processes become more efficient and competition increases, potentially reducing costs. Additionally, as research continues to validate its benefits for specific health conditions, the value proposition may strengthen for targeted applications.

Hydroxytyrosol in its pure form is relatively unstable due to its potent antioxidant properties, which make it highly reactive with oxygen. In powder form and under optimal storage conditions (low temperature, absence of light, oxygen, and moisture), pure hydroxytyrosol typically has a shelf life of 12-24 months. In supplement formulations, the shelf life varies significantly depending on the specific formulation, stabilization methods, and packaging. Properly formulated and packaged hydroxytyrosol supplements typically have a shelf life of 18-36 months.

Liquid formulations generally have shorter shelf lives (12-18 months) compared to solid formulations like capsules or tablets. In olive oil, hydroxytyrosol content gradually decreases over time, with studies showing approximately 40-50% reduction after 12 months of storage under typical conditions. This degradation is accelerated by exposure to light, heat, and oxygen. Stabilized forms of hydroxytyrosol, such as phospholipid complexes, microencapsulated forms, or specific ester derivatives, may offer improved stability and longer shelf life.

Products with added antioxidants or stabilizers (such as vitamin E, ascorbyl palmitate, or rosemary extract) may maintain potency longer than those without such additives.

Store hydroxytyrosol supplements in their original container with the lid tightly closed to protect from moisture and oxygen exposure. Keep in a cool, dry place away from direct sunlight and heat sources. Optimal temperature range is 59-77°F (15-25°C). Refrigeration is recommended for liquid formulations and may extend the shelf life of all hydroxytyrosol products, though it is not strictly necessary if other storage conditions are optimal.

Avoid freezing liquid formulations, as freeze-thaw cycles can accelerate degradation. Protect from light by storing in opaque or amber containers, as hydroxytyrosol is photosensitive and can degrade when exposed to light, particularly UV radiation. Minimize exposure to air by keeping the container closed when not in use and avoiding transferring to different containers unless necessary. For olive oil as a source of hydroxytyrosol, store in dark glass bottles, tightly sealed, and away from heat sources like stoves.

Refrigeration of olive oil is controversial but may help preserve polyphenol content in warm climates. If the product changes color significantly (becoming darker), develops an unusual odor, or shows visible signs of degradation, it may have lost potency and should be replaced. For maximum stability of hydroxytyrosol in cooking applications, add olive oil at the end of cooking or use it in cold applications to minimize heat-induced degradation of polyphenols.

Exposure to oxygen (oxidation is the primary degradation pathway for hydroxytyrosol), Exposure to light, particularly UV light, which accelerates oxidation reactions, High temperatures (above 86°F/30°C) significantly accelerate degradation, Alkaline conditions cause rapid degradation through oxidation and structural changes, High humidity, which can promote hydrolysis and microbial growth in some formulations, Presence of metal ions, particularly iron and copper, which catalyze oxidation reactions, Enzymatic degradation in some natural sources (such as olive oil) due to polyphenol oxidase activity, Prolonged exposure to air after opening the container, Freeze-thaw cycles, which can disrupt the structure of some formulations, Microbial contamination, particularly in liquid formulations or products with high moisture content, Chemical interactions with other compounds in complex formulations, Extended storage time, even under optimal conditions, leads to gradual degradation

Synthesis Methods

Natural Sources

Quality Considerations

Hydroxytyrosol itself has a relatively brief history as an identified compound, but its primary source—olive oil—has one of the longest and richest histories of any medicinal food. The olive tree (Olea europaea) has been cultivated in the Mediterranean region for at least 6,000 years, with archaeological evidence of olive oil production dating back to 4500 BCE. While ancient civilizations were unaware of hydroxytyrosol specifically, they recognized the medicinal properties of olive oil and olive products. In ancient Greece, Hippocrates, often called the ‘father of medicine,’ referred to olive oil as ‘the great healer’ and documented its use for over 60 different conditions.

He specifically recommended olive oil for skin conditions, wounds, burns, gynecological ailments, and as a general tonic for health and longevity. Ancient Egyptians used olive oil in their mummification processes, cosmetics, and medicines, considering it sacred and associated with purification. Romans continued this tradition, with Pliny the Elder documenting numerous medicinal uses for olive oil in his ‘Natural History’ in the 1st century CE. Throughout the Mediterranean, olive leaves were traditionally brewed into teas to treat fever, malaria, and infections—applications we now know may be related to the oleuropein content, which is metabolized to hydroxytyrosol.

The specific compound hydroxytyrosol was not isolated and identified until the mid-20th century, with significant research beginning in the 1990s as analytical techniques improved. The scientific interest in hydroxytyrosol was largely sparked by epidemiological studies on the Mediterranean diet, particularly the landmark Seven Countries Study initiated by Ancel Keys in the 1950s, which identified the remarkably low rates of cardiovascular disease in Mediterranean populations despite relatively high fat consumption. As researchers sought to understand this ‘Mediterranean paradox,’ attention turned to olive oil’s unique polyphenol content, eventually leading to the identification of hydroxytyrosol as one of its most bioactive components. The first commercial hydroxytyrosol extracts became available in the early 2000s, initially as ingredients for cosmetic applications and later as dietary supplements.

A significant milestone in hydroxytyrosol’s modern history came in 2011 when the European Food Safety Authority (EFSA) approved a health claim for olive oil polyphenols, stating that daily consumption of 5 mg of hydroxytyrosol and its derivatives contributes to the protection of blood lipids from oxidative damage. This was one of the first approved health claims for a polyphenol in Europe and significantly increased both scientific and commercial interest in hydroxytyrosol. In recent years, sustainable production of hydroxytyrosol has become a focus, with new methods developed to extract it from olive oil byproducts such as olive mill wastewater and olive pomace, which were traditionally considered waste products with environmental disposal challenges. This has transformed a potential environmental problem into a valuable resource for bioactive compounds.

Today, hydroxytyrosol is available in various forms, from olive oil and olive extracts to purified supplements, and research continues to expand our understanding of its diverse health benefits beyond its traditional uses.

Schwingshackl L, et al. Effects of olive oil on markers of inflammation and endothelial function: A systematic review and meta-analysis. Nutrients. 2015;7(9):7651-7675. This meta-analysis of 30 randomized controlled trials found that olive oil interventions significantly reduced C-reactive protein and interleukin-6 levels compared to controls. While not specific to hydroxytyrosol, the authors noted that the phenolic content of olive oil (including hydroxytyrosol) likely contributed to these anti-inflammatory effects., Hohmann CD, et al. Effects of high phenolic olive oil on cardiovascular risk factors: A systematic review and meta-analysis. Phytomedicine. 2015;22(6):631-640. This meta-analysis of 26 studies found that high-phenolic olive oil (rich in hydroxytyrosol) significantly improved measures of oxidative stress and endothelial function compared to low-phenolic olive oil. The authors concluded that the phenolic compounds, particularly hydroxytyrosol, were responsible for these cardiovascular benefits., Peyrol J, et al. Hydroxytyrosol in the prevention of the metabolic syndrome and related disorders. Nutrients. 2017;9(3):306. This systematic review examined the effects of hydroxytyrosol on components of metabolic syndrome. The authors concluded that hydroxytyrosol shows promise for improving lipid profiles, insulin sensitivity, and oxidative stress based on both animal and human studies, though they noted the need for larger clinical trials.

Effects of Hydroxytyrosol Supplementation on Cognitive Function in Older Adults (NCT04919811), Hydroxytyrosol for Prevention of Diabetic Retinopathy Progression (NCT03939624), Olive Polyphenols and Mild Cognitive Impairment (NCT03824197), Hydroxytyrosol Supplementation and Exercise Performance in Athletes (NCT04048330), Effects of Hydroxytyrosol on Non-Alcoholic Fatty Liver Disease (NCT04378075)