Chlorogenic acid

Chlorogenic acid is a naturally occurring antioxidant compound found naturally in coffee beans. It is mainly used for weight loss and to lower blood pressure. However, scientific research shows that chlorogenic acid may also help to lower blood sugar levels, improve mood and fight infections.

What is chlorogenic acid?

Chlorogenic acid is a polyphenol compound found in coffee beans and various types of coffee, including green coffee. It is also found in other foods such as apples, blueberries, tomatoes, strawberries and potatoes (1, 2, 3, 4, 5). Chlorogenic acid is primarily supplemented in the form of green coffee bean extracts. Chlorogenic acid has a number of positive effects on health. However, scientific research suggests that chlorogenic acid may also help to lower blood sugar levels, improve mood and fight infections (6). Note: Many studies refer to chlorogenic acids (plural) rather than chlorogenic acid. The plural form refers to a family of related molecules known as polyphenol esters and is not exclusive to the effects of the individual esterified molecule chlorogenic acid.

Natural sources of chlorogenic acid

Green coffee bean extracts are the primary natural source of chlorogenic acid, which is also used in supplements (7).

Chlorogenic acid is also a component of coffee and many fruits and vegetables including apples, pears, blueberries, tomatoes, strawberries and potatoes. It is also found in bamboo, hawthorn and Athrixia phylicoides (1, 2, 3, 4, 5).

Mechanisms of action

Chlorogenic acid exerts its effects primarily by inhibiting the enzyme alpha-glucosidase, which is responsible for the breakdown of carbohydrates. This reduces the absorption of carbohydrates and glucose during digestion. (8, 9).

Chlorogenic acid also has a mild stimulating effect, which is one third of the effect of caffeine. This effect is mediated by the breakdown of its by-products caffeic acid and m-coumaric acid (10).

Chlorogenic acid may also act via the following mechanisms:

Inhibition of 11-βHSD1, an enzyme involved in the production of hormones that increase blood pressure (11).
Activation of the GABAa receptor by binding to the benzodiazepine docking sites, resulting in an anxiolytic effect (12).
Increasing levels of glucagon-like peptide 1 (GLP-1), a hormone that increases insulin levels in the blood and lowers blood glucose levels (12).
Activation of Peroxisome Proliferator-Activated Receptor alpha (PPAR-alpha), which leads to increased production of heat and increased fat loss (14).
Reduction of body fat by reducing the levels of triglycerides, LDL cholesterol and VLDL (15).
Preventing the absorption and production of fats (by inhibiting fatty acid synthase) while increasing the breakdown of fats (by stimulating beta-oxidation) (16).
Inhibition of HMG-CoA, the enzyme responsible for the production of cholesterol and the primary target of statin drugs (15).
Improving the survival of dopamine-producing brain cells by inhibiting microglial activation (17),
Inhibition of acetylcholinesterase, resulting in improved cognitive function and memory (18).

Possible health benefits of chlorogenic acid

Chlorogenic acid could lower blood pressure

A single dose of chlorogenic acid or polyphenols isolated from coffee lowered blood pressure in 2 small studies involving 38 healthy volunteers (19, 20). The consumption of coffee rich in chlorogenic acid also improved the function of blood vessels and lowered blood pressure in 4 clinical studies involving 314 healthy volunteers (11, 21, 22, 23). In 4 clinical studies involving 200 subjects with high blood pressure, taking an extract of green coffee beans rich in chlorogenic acid lowered blood pressure by improving vasodilatation. Isolated chlorogenic acid also reduced blood pressure in another study of 28 hypertensive patients (24, 25, 26, 27, 28). A single dose of chlorogenic acid (30 to 600 mg) reduced blood pressure in hypersensitive rats and also improved blood vessel function (29). Taken together, these study results suggest that chlorogenic acid could lower blood pressure and improve blood vessel function in both healthy people and people with high blood pressure. However, it is important in this context that chlorogenic acid should never be used as a substitute for blood pressure medication. Concomitant use should also be discussed with the attending physician in order to avoid interactions with medication.

Chlorogenic acid could lower high blood sugar levels

Several studies show that chlorogenic acid can reduce fasting blood glucose levels as well as peak blood glucose and insulin levels after a meal. In 57 healthy women, a chlorogenic acid extract reduced pre-meal blood glucose levels and an indicator of diabetes (HbA1c). Coffee reduced insulin resistance in 3 small studies with 30 healthy volunteers (30, 31, 32, 33). In a clinical study with 15 overweight men, chlorogenic acid lowered blood glucose and insulin peak values after an oral 75 gram glucose tolerance test (34). Two different dietary supplements containing chlorogenic acid were able to improve insulin sensitivity and blood lipid profile in 2 clinical trials with 130 overweight subjects (35, 36). In another study of 30 prediabetic patients (impaired glucose tolerance), 400 mg of chlorogenic acid three times a day reduced fasting blood glucose levels and insulin secretion, while also improving insulin sensitivity (37). A green coffee bean extract reduced fasting blood glucose levels, blood lipid levels and body fat in a clinical study of 43 patients with metabolic syndrome. A natural supplement containing chlorogenic acid and several other plant extracts had similar effects in another study of 78 subjects with this condition (38, 39). Chlorogenic acid also led to lower blood glucose levels in fasting mice and reduced diabetes markers in diabetic mice (14, 40, 41). The available study results suggest that chlorogenic acid may help improve glycemic control and insulin sensitivity in both healthy and overweight people.

Chlorogenic acid could support weight loss

In a clinical trial involving 12 healthy volunteers, chlorogenic acid-enriched coffee increased weight loss by reducing sugar absorption. In another clinical study with 9 healthy volunteers, chlorogenic acid increased fat burning during sleep (42, 43). Coffee enriched with chlorogenic acid reduced body weight and risk factors for heart disease in a clinical study with 52 subjects. In subjects with high cholesterol levels, chlorogenic acid also reduced blood lipid levels (triglyceride levels, total cholesterol and "bad" LDL and VLDL cholesterol (22). In another clinical trial involving 16 obese subjects, green coffee bean extract reduced weight, BMI and body fat percentage when taken for 22 weeks (7). Both green coffee bean extracts and natural supplements with chlorogenic acid were able to reduce body weight and blood lipid levels in 2 clinical studies with 121 subjects with metabolic syndrome (38, 39). Chlorogenic acid also reduced body weight, body mass index and waist circumference in another study of 30 patients with prediabetes (impaired glucose tolerance) (37). However, dark-roasted coffee (which is low in chlorogenic acid) was more effective than light-roasted coffee in reducing body weight in a clinical study of 30 healthy volunteers (44). A study conducted on obese mice fed a high-fat diet also found that chlorogenic acid was able to induce a loss of body fat and an increase in body heat production (14). All in all, the results of this and other studies suggest that chlorogenic acid can help reduce body fat and lose weight. However, more exercise and dietary improvements are likely to be more effective, with a combination of lifestyle changes and chlorogenic acid likely to have the best effect.

Chlorogenic acid could improve mood

In a clinical study of 39 elderly people, 3 cups of decaffeinated coffee fortified with chlorogenic acid improved mood and alertness (45). In another clinical study of 15 cyclists, consumption of coffee rich in chlorogenic acid (300 ml per day for 2 weeks) showed no effect on post-exercise inflammation and oxidative damage, but reduced mood swings (46). In contrast, in another study of 60 elderly people, isolated chlorogenic acid (540 mg) reduced feelings of fatigue, agitation and headaches, but worsened mood (47). In mice treated with a chlorogenic acid-enriched extract of E. ulmoides, 7 days of treatment reduced depression-like symptoms. In brain cells, the treatment maintained cell growth and structure and increased serotonin release (48). Although these study results are promising, further human studies are needed before definitive conclusions can be drawn about the exact effects of chlorogenic acid on mood in humans.

Chlorogenic acid could improve cognitive function

In a clinical study of 38 healthy humans, consumption of a beverage with added chlorogenic acid for 16 weeks improved performance in some cognitive functions (motor and psychomotor speed, executive function and shift in attention) (49). In mice treated with a neurotoxic drug (scopolamine), chlorogenic acid improved short-term memory and working memory and reversed cognitive impairment by inhibiting acetylcholinesterase (18). In mice with Alzheimer's disease, chlorogenic acid improved spatial memory and working memory. Cell studies indicate a neuroprotective effect against beta-amyloid proteins - the main cause of Alzheimer's disease (50). In mice and in cell cultures of brain cells, chlorogenic acid improved the survival of brain cells containing dopamine. This suggests potential benefits for people with neurodegenerative diseases such as Parkinson's. Indeed, in dopamine-containing brain cells, chlorogenic acid prevented the toxic effects of a protein involved in this disease (alpha-synuclein) (17, 51). Although these results are promising, most of the studies were conducted in mice, which means that further human studies are needed before definitive conclusions can be drawn.

Chlorogenic acid could help with bacterial infections

In a study of 45 subjects, gargling twice daily for 2 weeks with a mouthwash containing green coffee bean extract reduced salivary concentrations of a bacterium (Streptococcus mutans) that causes tooth decay and gingivitis (52). In mice infected with an antibiotic-resistant "superbacterium" (Staphylococcus aureus), chlorogenic acid prevented the harmful effects of this bacterium and reduced the number of bacteria. This was achieved by inhibiting the bacterial enzyme sortase A (53). These isolated results are promising, but further studies are needed to confirm the antibacterial effects of chlorogenic acid.

Chlorogenic acid could alleviate oxidative and inflammatory stress

Several studies conducted with rodents and cells have shown that chlorogenic acid has antioxidant and anti-inflammatory effects (55, 56, 57, 58, 59, 60). This antioxidant activity could be attributed to the increased production of antioxidant proteins such as glutathione, as well as vitamins C and E. In addition, chlorogenic acid reduced oxidative stress by lowering the levels of oxidative proteins and reactive oxygen species (41, 58, 59). Cell-based studies have also shown that chlorogenic acid can reduce cell death, prevent DNA fragmentation and lower levels of reactive oxygen species and nitrogen species (ROS/RNOS) (61).

Chlorogenic acid could have anti-cancer effects

Investigations into the potential anti-cancer effects of chlorogenic acid are still at an early stage, which means that chlorogenic acid should under no circumstances be used as a substitute for conventional cancer therapy. Application of chlorogenic acid to the skin prevented the growth of skin tumors in mice (62). In mice fed large amounts of bile acids, supplementing their diet with chlorogenic acid prevented the development of colon cancer (63). In cell-based studies, chlorogenic acid reduced the growth of the following cancers by inhibiting pathways involved in tumor growth (AP-1, NF-kappaB, MAPK) and killed these cells by increasing the production of reactive oxygen species and blocking potentially carcinogenic proteins (EOK1/2):

Lung cancer (60, 64)
Colorectal cancer (65)
Breast cancer (66, 67)
Liver cancer (68)

Limitations and cautions

Most of the studies investigated the effects of green coffee bean extracts, which contain a number of other active ingredients in addition to chlorogenic acid. The specific contribution of chlorogenic acid to the observed effects is therefore not clear. Further studies with isolated chlorogenic acid are therefore needed to conclusively confirm its effects. In addition, many of the studies were conducted with mice. Thus, further human studies are needed to confirm these preliminary results. In addition, a number of studies - particularly studies using green coffee bean extracts - were funded by companies that market these products. These results are not necessarily invalid, but one must always be critical when looking at industry-funded studies.

Side effects and precautions

There have been reports of allergies to green coffee bean extracts, the natural source of chlorogenic acid. The symptoms were primarily asthma attacks. However, compounds other than chlorogenic acid contained in coffee appear to be responsible for these effects (69, 70). Since green coffee bean extract contains caffeine, it may have some undesirable side effects. People who are sensitive to caffeine should avoid taking such extracts late at night to prevent sleep disturbances. Although side effects were rarely reported in studies, many studies only examined chlorogenic acid supplements over a limited period of time, so further long-term studies are needed to identify other potential side effects.

Interactions with medications

Due to its potential antihypertensive effects, chlorogenic acid may cause an excessive drop in blood pressure in people taking antihypertensive medication. Chlorogenic acid could increase the effects of metformin - a drug used to treat high blood sugar levels. However, this effect was only achieved at much higher concentrations of chlorogenic acid than are likely to occur with chlorogenic acid supplementation (71).

Dosage

As there are no official intake recommendations, one can only rely on empirical values and dosage information from supplement manufacturers. Different green coffee bean extracts may also contain different amounts of chlorogenic acid. The dosages recommended by manufacturers range from 240 to 3,000 mg per day, depending on the supplement in question.

User experiences

These are merely testimonials that are not scientifically based and are therefore purely informative and should not be considered as recommendations. Users who wanted to benefit from the effects of chlorogenic acid usually did not supplement with the pure substance, but used extracts from green coffee beans. Most users use chlorogenic acid to support weight loss and lower blood pressure. Many of these users were satisfied with the results. Most dissatisfied users complained that they felt no effect after taking such an extract.

The primary adverse side effects reported include anxiety and restlessness, rapid heartbeat and insomnia. However, these effects are likely to be due to the caffeine content of green coffee. Mild weight loss (possibly due to both caffeine and chlorogenic acid) has also been reported by some users who had not used chlorogenic acid for this purpose.