Chlorogenic Acid

• Antioxidant protection
• Anti-inflammatory
• Metabolic regulation
• Cardiovascular support

• Hepatoprotection
• Neuroprotection
• Blood glucose regulation
• Weight management
• Antimicrobial activity
• Anticancer properties

Chlorogenic acid (CGA) exerts its diverse biological effects through multiple mechanisms at the molecular level. As a potent antioxidant, CGA effectively neutralizes free radicals through direct scavenging of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Its unique chemical structure, featuring a catechol group (from caffeic acid) and a quinic acid moiety, allows it to form a resonance-stabilized phenoxy radical that accounts for its potent antioxidant activity. The catechol moiety is particularly effective at donating hydrogen atoms to neutralize free radicals, while the quinic acid portion enhances its stability and bioactivity.

Beyond direct radical scavenging, CGA enhances the body’s endogenous antioxidant defenses by activating the Nrf2 (Nuclear factor erythroid 2-related factor 2) signaling pathway. This activation leads to increased expression of antioxidant enzymes such as glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). CGA exhibits strong anti-inflammatory properties by inhibiting the NF-κB (nuclear factor kappa B) signaling pathway, a master regulator of inflammatory responses. It suppresses the phosphorylation and degradation of IκB (inhibitor of kappa B), preventing the nuclear translocation of NF-κB and subsequent expression of pro-inflammatory genes.

CGA also inhibits the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). Additionally, it suppresses the activity of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), thereby reducing the production of prostaglandins and nitric oxide that contribute to inflammation. For metabolic regulation, CGA plays a significant role in glucose and lipid metabolism. It inhibits glucose-6-phosphatase, reducing hepatic glucose production and thereby helping to regulate blood glucose levels.

CGA also activates AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, which promotes glucose uptake in skeletal muscle and reduces lipid accumulation in the liver. Furthermore, CGA inhibits the intestinal absorption of glucose by inhibiting sodium-dependent glucose transporters (SGLTs), leading to reduced postprandial glucose spikes. In the cardiovascular system, CGA improves endothelial function by enhancing nitric oxide (NO) production through increased expression and activity of endothelial nitric oxide synthase (eNOS). It also reduces lipid peroxidation in blood vessels and inhibits platelet aggregation, contributing to its cardioprotective effects.

CGA positively influences lipid metabolism by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, and by promoting cholesterol efflux from cells. For weight management, CGA may help reduce body weight and fat accumulation through multiple mechanisms. It increases fat oxidation by upregulating peroxisome proliferator-activated receptor alpha (PPARα) and its target genes involved in fatty acid oxidation. CGA also reduces the expression of genes involved in adipogenesis and lipogenesis, such as peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid synthase (FAS).

Additionally, it may modulate gut microbiota composition, favoring beneficial bacteria that contribute to improved metabolic health. In the liver, CGA provides hepatoprotection by enhancing the activity of phase II detoxification enzymes, facilitating the elimination of toxins and reducing oxidative stress in hepatocytes. It also inhibits lipid peroxidation in liver cell membranes and prevents mitochondrial dysfunction, which are key factors in various liver diseases. For neuroprotection, CGA crosses the blood-brain barrier and exerts multiple beneficial effects on neuronal cells.

It reduces oxidative stress in the brain by scavenging free radicals and enhancing antioxidant enzyme activities. CGA also suppresses neuroinflammation by inhibiting microglial activation and reducing the production of pro-inflammatory cytokines in the brain. Additionally, it may protect against neurodegenerative diseases by inhibiting the aggregation of amyloid-beta peptides and tau protein, which are key pathological features of Alzheimer’s disease. CGA exhibits antimicrobial properties by disrupting bacterial cell membranes, inhibiting bacterial enzymes, and interfering with quorum sensing mechanisms.

It has shown activity against various bacteria, fungi, and viruses, including Staphylococcus aureus, Escherichia coli, and herpes simplex virus. For anticancer effects, CGA demonstrates potential through multiple mechanisms, including cell cycle arrest, induction of apoptosis in cancer cells, inhibition of angiogenesis, and modulation of various signaling pathways involved in cell proliferation and survival. It also inhibits matrix metalloproteinases (MMPs), which are involved in tumor invasion and metastasis.

The optimal dosage range for chlorogenic acid (CGA) supplements is typically between 200-1000 mg per day, based on clinical studies. For general antioxidant support and preventive benefits, 200-400 mg daily is commonly recommended. Higher doses (500-1000 mg) have been used in studies targeting specific health conditions such as blood glucose management, weight loss, and cardiovascular support. Most people obtain CGA primarily through dietary sources, particularly coffee, with average dietary intake estimated at 100-300 mg per day from coffee and other plant foods.

The dosage may vary depending on the form of supplementation, with green coffee bean extract typically standardized to contain 45-50% CGA.

Chlorogenic acid (CGA) has moderate oral bioavailability, estimated at approximately 30-40% in humans. The absorption occurs through multiple mechanisms and sites in the gastrointestinal tract. In the small intestine, a small portion of CGA is absorbed intact through active transport mechanisms involving monocarboxylic acid transporters (MCTs). However, a significant portion of ingested CGA reaches the colon, where it is metabolized by gut microbiota.

The colonic microflora hydrolyzes CGA to release caffeic acid and quinic acid, which are then either absorbed or further metabolized. The absorbed CGA and its metabolites undergo extensive phase II metabolism in the liver, primarily through glucuronidation, sulfation, and methylation, which affects their bioactivity and distribution in the body. The bioavailability of CGA is influenced by various factors, including food matrix, gut microbiota composition, and individual genetic variations in metabolizing enzymes.

Liposomal encapsulation: Can increase bioavailability by 2-3 times by protecting CGA from degradation and enhancing cellular uptake, Nanoparticle formulations: May increase bioavailability by up to 3-4 times through improved solubility and cellular penetration, Co-administration with piperine (black pepper extract): Can inhibit glucuronidation and increase bioavailability by approximately 30-60%, Phytosomal complexes: Binding CGA with phospholipids can enhance absorption by 2-3 times, Taking with a small amount of healthy fats: May enhance absorption of CGA, Consuming with probiotics: May enhance metabolism by gut microbiota, potentially increasing the production of bioactive metabolites, Sustained-release formulations: Can provide more consistent blood levels over time, Green coffee bean extract: Contains naturally occurring compounds that may enhance CGA absorption, Consuming with other antioxidants: Synergistic effects have been observed when combined with other antioxidants like vitamin C, vitamin E, or other phenolic compounds

For optimal absorption, chlorogenic acid supplements are best taken 30 minutes before meals or 2 hours after meals. However, if gastrointestinal discomfort occurs, it can be taken with food, preferably with a small amount of healthy fat to enhance absorption. For blood glucose management, taking CGA 30 minutes before meals may help reduce post-prandial glucose spikes by inhibiting glucose absorption in the intestine. For weight management, dividing the daily dose into 2-3 servings throughout the day may provide more consistent benefits.

For cardiovascular benefits, consistent daily dosing is more important than specific timing. When used for antioxidant and anti-inflammatory effects, morning administration may be preferable to align with the body’s natural circadian rhythms, though evidence is limited. The half-life of CGA and its metabolites in the body is relatively short (estimated at 2-5 hours), so divided doses throughout the day may provide more consistent benefits for certain conditions. For those consuming CGA primarily through coffee, morning consumption aligns with natural circadian rhythms and may provide optimal benefits, though the caffeine content should be considered for those sensitive to its effects.

Consuming the last dose of CGA at least 4-6 hours before bedtime is recommended to avoid potential sleep disturbances, particularly if the supplement contains caffeine or is derived from coffee beans.

• Gastrointestinal discomfort (mild nausea, stomach upset, diarrhea)
• Headache (particularly in caffeine-sensitive individuals if derived from coffee sources)
• Increased heart rate (rare, more common with green coffee bean extracts that contain residual caffeine)
• Sleep disturbances (rare, particularly when taken in the evening or with caffeine-containing extracts)
• Allergic reactions (rare, more common in individuals with allergies to plants containing chlorogenic acid)
• Anxiety or jitteriness (rare, more common with caffeine-containing extracts)
• Temporary increase in homocysteine levels (at high doses)
• Potential pro-oxidant effects at very high doses (theoretical concern based on in vitro studies)

• Known hypersensitivity or allergy to chlorogenic acid or plants high in chlorogenic acid
• Pregnancy and breastfeeding (due to insufficient safety data, particularly for isolated supplements)
• Bleeding disorders (theoretical concern due to potential antiplatelet effects)
• Scheduled surgery (discontinue 2 weeks before due to potential antiplatelet effects)
• Severe liver or kidney disease (use with caution due to limited research)
• Anxiety disorders (caution with caffeine-containing extracts)
• Sleep disorders (avoid taking in the evening, particularly caffeine-containing extracts)
• Hyperhomocysteinemia (high doses may increase homocysteine levels)
• Glaucoma (caution with caffeine-containing extracts)
• Osteoporosis (high doses of caffeine-containing extracts may affect calcium absorption)

• Anticoagulant and antiplatelet medications (may enhance blood-thinning effects)
• Antihypertensive drugs (may enhance blood pressure-lowering effects)
• Antidiabetic medications (may enhance blood glucose-lowering effects, requiring dose adjustments)
• Stimulant medications (additive effects with caffeine-containing extracts)
• Hepatotoxic drugs (theoretical concern for additive effects at very high doses)
• Drugs metabolized by cytochrome P450 enzymes (potential for mild interactions)
• Iron supplements (may reduce absorption if taken simultaneously)
• Lithium (caffeine-containing extracts may affect lithium levels)
• MAO inhibitors (caution with caffeine-containing extracts)
• Medications for osteoporosis (high doses of caffeine-containing extracts may affect calcium metabolism)

No official upper limit has been established. Most clinical studies have used doses up to 1000 mg daily without significant adverse effects. However, for long-term use, doses above 800 mg daily are not recommended without medical supervision due to limited long-term safety data. Higher doses (>1000 mg/day) may increase homocysteine levels in some individuals, which is a potential cardiovascular risk factor.

For green coffee bean extracts, the caffeine content should be considered when determining the upper limit, with total caffeine intake from all sources not exceeding 400 mg per day for most healthy adults.

In the United States, chlorogenic acid is not approved as a drug but is generally recognized as safe (GRAS) as a food component naturally present in many common foods, particularly coffee and fruits. As a dietary supplement ingredient, it falls under the Dietary Supplement Health and Education Act (DSHEA) of 1994, which means manufacturers cannot make specific disease treatment claims but can make structure/function claims about its effects on normal body functions. Green coffee bean extract, which is rich in chlorogenic acid, is also regulated as a dietary supplement ingredient. The FDA has issued warning letters to some companies marketing green coffee bean extract with exaggerated weight loss claims, emphasizing the need for accurate and substantiated marketing.

For cosmetic use, chlorogenic acid is approved as a skin conditioning agent and antioxidant. The FDA does not require pre-market approval for dietary supplements containing chlorogenic acid, but manufacturers are responsible for ensuring safety and accurate labeling.

Eu: In the European Union, chlorogenic acid is recognized as a natural food component and is permitted in food supplements under the Food Supplements Directive (2002/46/EC). It must comply with general food safety regulations. The European Food Safety Authority (EFSA) has evaluated health claims related to polyphenols in coffee, including chlorogenic acid, and has not approved specific health claims due to insufficient evidence. For cosmetic use, it is listed in the European Inventory of Cosmetic Ingredients as an antioxidant and skin conditioning agent. Novel food authorization may be required for certain applications or extraction methods of chlorogenic acid.

Canada: Health Canada permits chlorogenic acid in natural health products (NHPs) with appropriate safety data. It is listed in the Natural Health Products Ingredients Database (NHPID) with antioxidant and metabolic support roles. Green coffee bean extract is also permitted as an NHP ingredient. Product license applications must include quality, safety, and efficacy information. Health Canada has approved some limited claims for green coffee bean extract related to antioxidant activity.

Australia: The Therapeutic Goods Administration (TGA) permits chlorogenic acid in listed complementary medicines. It is included in the Australian Inventory of Chemical Substances (AICS) and permitted for use in cosmetics and personal care products. Green coffee bean extract is also permitted in listed medicines. Specific therapeutic claims require higher levels of evidence and registration as a registered medicine.

Japan: In Japan, chlorogenic acid is approved as a food component and is also permitted in Foods for Specified Health Uses (FOSHU) with appropriate substantiation. The Ministry of Health, Labour and Welfare regulates its use in various applications. Some functional food products containing chlorogenic acid have received FOSHU approval for claims related to reducing the absorption of glucose from meals.

China: The National Medical Products Administration (NMPA) permits chlorogenic acid in both cosmetic formulations and health food products with appropriate registration. Traditional Chinese Medicine formulations containing chlorogenic acid-rich herbs have separate regulatory pathways. Some health food products containing chlorogenic acid have received approval for claims related to antioxidant activity and weight management.

India: The Food Safety and Standards Authority of India (FSSAI) recognizes chlorogenic acid as a natural food component. For use in Ayurvedic and traditional formulations, it falls under AYUSH regulations when present in natural herbal extracts. Nutraceutical products containing chlorogenic acid must comply with the FSSAI regulations for health supplements and nutraceuticals.

Medium

For standard chlorogenic acid supplements (200-400 mg daily): $0.30-$1.00 per day. For higher potency supplements (500-1000 mg daily): $0.75-$2.50 per day. For green coffee bean extract (standardized to 45-50% chlorogenic acid): $0.40-$1.50 per day. Enhanced delivery forms (liposomal, phytosomal): $1.50-$4.00 per day. Decaffeinated green coffee bean extract: $0.50-$1.80 per day.

Chlorogenic acid offers good value for its cost, particularly when considering its multiple health benefits. For general antioxidant support, more cost-effective alternatives exist (such as vitamin C), but chlorogenic acid’s unique mechanisms and potential specific benefits for glucose metabolism, weight management, and cardiovascular health may justify the cost for certain health goals. The best value is typically found in green coffee bean extract standardized to 45-50% chlorogenic acid, which provides a cost-effective source of the compound along with other potentially beneficial coffee polyphenols. Pure chlorogenic acid supplements are generally more expensive but may be preferred by those seeking to avoid other coffee components or those with caffeine sensitivity (though decaffeinated options are available).

Enhanced delivery systems significantly increase cost but may provide better value through improved bioavailability, especially for individuals with absorption issues or those seeking specific therapeutic effects. For weight management and blood glucose regulation, the moderate price point of chlorogenic acid supplements may offer good value compared to more expensive prescription medications or medical interventions, though effects are generally more modest. Consumers should be cautious of very low-priced products, which may contain lower purity or potency than claimed. Similarly, extremely high-priced products often reflect marketing rather than superior quality.

For most health applications, moderate price point products from reputable manufacturers offer the best balance of quality and value. Food sources of chlorogenic acid (such as coffee, apples, and artichokes) provide the most cost-effective way to obtain this compound, though in lower concentrations than supplements. A cup of coffee typically contains 70-350 mg of chlorogenic acid, depending on the type of coffee, roasting degree, and brewing method, making it an economical source for those who enjoy coffee. For those seeking the benefits of chlorogenic acid without caffeine, decaffeinated coffee still retains most of its chlorogenic acid content and may be a cost-effective alternative to supplements.

Pure chlorogenic acid powder typically has a shelf life of 1-2 years when properly stored. Capsules and tablets generally have a shelf life of 1-2 years. Green coffee bean extracts standardized for chlorogenic acid content usually have a shelf life of 1-3 years, depending on the formulation and storage conditions. Liquid formulations containing chlorogenic acid usually have shorter shelf lives of 6-12 months after opening due to increased vulnerability to oxidation and microbial contamination.

Store in a cool, dry place away from direct sunlight and heat sources. Ideal temperature range is 15-25°C (59-77°F). Keep container tightly closed when not in use to prevent moisture absorption. For powder forms, use a desiccant in the container if the original packaging doesn’t include one.

Refrigeration is not necessary but may extend shelf life, particularly for liquid formulations after opening. Avoid storing near strong-smelling substances as chlorogenic acid may absorb odors. Chlorogenic acid is more stable under slightly acidic conditions (pH 4-6) than under neutral or basic conditions, so formulations with appropriate pH buffering may have extended stability. For maximum stability, store chlorogenic acid products in an inert atmosphere (e.g., nitrogen-flushed containers) when possible.

Exposure to light (especially UV light) accelerates oxidation, High temperatures (above 30°C/86°F) significantly reduce stability, Moisture and humidity promote hydrolysis and degradation, Alkaline pH conditions (pH > 7) increase degradation rate, Presence of metal ions (particularly iron and copper) catalyzes oxidation, Oxygen exposure leads to oxidative degradation, Microbial contamination can occur in liquid formulations without proper preservatives, Repeated freeze-thaw cycles accelerate degradation, Enzymatic degradation by esterases can occur in some formulations, Roasting process (in coffee) significantly reduces chlorogenic acid content, with up to 60% loss during medium roasting, Brewing methods affect extraction efficiency, with espresso methods generally extracting more chlorogenic acid than filter methods, Storage of brewed coffee leads to gradual degradation of chlorogenic acid, with significant losses after 24 hours at room temperature

Synthesis Methods

Natural Sources

Quality Considerations

Chlorogenic acid has a rich history of indirect traditional use, primarily through the consumption of plants and foods that naturally contain high levels of this compound. While chlorogenic acid itself was not specifically identified or isolated until the 19th century, many traditional medicinal plants and beverages rich in this compound have been used for centuries across different cultures. Coffee, the richest source of chlorogenic acid, has been consumed for its stimulating and medicinal properties since at least the 15th century in the Arabian Peninsula, before spreading globally. Traditional Arabic and Ethiopian medicine recognized coffee’s ability to enhance alertness, improve digestion, and reduce inflammation, effects that we now know are partly attributable to its chlorogenic acid content.

In traditional European herbal medicine, plants rich in chlorogenic acid such as artichoke leaves were used for liver support, digestive health, and as a diuretic. Artichoke leaf extracts, standardized for their chlorogenic acid content, continue to be used in modern phytotherapy for these purposes. In Traditional Chinese Medicine (TCM), herbs containing chlorogenic acid like honeysuckle (Lonicera japonica) and eucommia bark (Eucommia ulmoides) were used to clear heat, reduce inflammation, and treat infections. These plants were often included in formulations for febrile conditions, skin disorders, and liver support.

In Native American healing traditions, various berries and fruits containing chlorogenic acid were used for their medicinal properties. These were often used for general wellness, digestive support, and as natural preservatives for food. Yerba mate, a traditional South American beverage rich in chlorogenic acid, has been consumed for centuries by indigenous peoples of Paraguay, Argentina, and Brazil for its energizing, digestive, and health-promoting properties. The modern scientific interest in chlorogenic acid began in the 19th century when it was first isolated and characterized, but significant research into its health benefits only gained momentum in the late 20th century with the growing interest in plant phenolics and antioxidants.

The discovery of chlorogenic acid’s potential role in glucose metabolism and weight management in the early 2000s led to increased interest in green coffee bean extract as a dietary supplement. This was further popularized by media attention, including a feature on the Dr. Oz television show in 2012, which significantly increased public awareness and commercial interest in chlorogenic acid supplements. In contemporary food science, chlorogenic acid has been recognized as an important bioactive compound in coffee and various fruits and vegetables.

The bitter taste associated with some of these foods is partly attributed to chlorogenic acid and its derivatives. Modern extraction and processing techniques have been developed to preserve or enhance the chlorogenic acid content of foods and beverages, recognizing its potential health benefits. Today, chlorogenic acid is available as a dietary supplement in various forms, including isolated compound, green coffee bean extract, and as part of complex plant extracts. It is also being investigated for potential applications in functional foods, cosmetics, and pharmaceuticals, representing a bridge between traditional plant-based healing and modern evidence-based approaches to health and wellness.

Several meta-analyses have examined the effects of chlorogenic acid or green coffee bean extract (rich in chlorogenic acid) on various health outcomes. A 2023 meta-analysis found significant weight loss effects with 500 mg daily chlorogenic acid supplementation. A 2015 meta-analysis demonstrated significant blood pressure-lowering effects. A 2020 meta-analysis showed improvements in glucose metabolism and insulin sensitivity with chlorogenic acid supplementation., Most meta-analyses note the need for larger, longer-term studies with standardized chlorogenic acid preparations to strengthen the evidence base.

Investigation of chlorogenic acid supplementation on endothelial function in adults with metabolic syndrome, Evaluation of chlorogenic acid for cognitive function in older adults, Combination therapy of chlorogenic acid with standard treatments for type 2 diabetes, Effects of chlorogenic acid on non-alcoholic fatty liver disease biomarkers, Long-term safety and efficacy of chlorogenic acid supplementation for weight management