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Chlorogenic Acid

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Coffee and Chlorogenic AcidDietary Sources of Chlorogenic acid

Chlorogenic acids are the active ingredient in Green Coffee Bean Extracts which have been made popular in recent times by celebrities like Dr. Oz and Oprah touting them as miracle weight loss cures.

The Dr. Oz show referred to it as “The green coffee bean that burns fat fast” and claims that no change to diet or exercise is needed in order to lose weight.

Studies have shown that chlorogenic acid reduces blood pressure and improves glucose metabolism as well as reducing the risk of some diseases like type II diabetes, liver disease, liver cancer, Parkinson’s disease and Alzheimer’s disease.

Chlorogenic acids are mostly found in coffee beans and the resulting brew but can also be found in other plants, including bamboo, potatoes, eggplant, tomatoes, apples, pears, peaches, nectarines, prunes, blueberries, strawberries, honeysuckle, hawthorn, sunflower leaves and seeds and tea.

Top foods rich in chlorogenic acid:
  • Coffee seeds  (50,000 – 100,000 parts per million)
  • Sunflower seeds (1900 – 28000 ppm)
  • Blueberries (3000 ppm)
  • Coriander/Chinese Parsley/Cilantro (305 – 320 ppm)
  • Potato (22 – 71 ppm)
  • Tomato (18 ppm)
  • Peanuts (12 ppm)
  • Wheat (5 ppm)
Benefits
Firstly, a word of caution

The majority of the studies into the effects of chlorogenic acid on humans have been sponsored by industry with a significant investment in the positive outcomes of those studies.  Funding bias or sponsorship bias is a well-known and recognised phenomenon.  In 2012, the Cochrane Collaboration published one of their famous systematic reviews into the issue, finding that

“Sponsorship of drug and device studies by the manufacturing company leads to more favorable results and conclusions than sponsorship by other sources.”

It was estimated that the effect of this bias resulted in a study outcome which was favourable to the sponsoring entity 25% more often than if the study were to be performed by a non-industry funded research group.  To take the most charitable view of this phenomenon we can view it as a subconscious desire by the researchers to do something nice for someone who has done something nice for them.  To take the least charitable view of this phenomenon we can view it as positive results being bought and paid for in an intentional manner, with complicity on both the part of the company and the researchers, or at least the lead researcher.  Either method may be the case, depending upon the rigour with which the research group implements ethics procedures.

It is also worth noting that some of the effects noted have come from laboratory animal studies where the dosage of chlorogenic acid is extremely high, as much as 400 mg per kg.  These dosages may not be safe in humans, or unrealistic to achieve given the cost and low concentration of chlorogenic acid in most commercially available supplements.  Human physiology is also not always the same as animal physiology, though generally researchers try and match the physiological process they are trying to study with an animal in which the process is most closely replicated to that in humans.

Slowed glucose absorption, reduced insulin spike after eating

 

Chlorogenic acids have long been recognised as potent antioxidants, however, interest in the compounds began increasing in the early 2000′s as researchers discovered that they could also slow down the absorption of glucose in the human gut, therefore reducing the insulin spike after a meal, an effect that is of significant benefit to those suffering from type II diabetes, insulin resistance, metabolic syndrome or polycystic ovarian syndrome.  A 2009 study found that blood glucose and insulin levels were significantly reduced 15 minutes into a glucose tolerance test, after ingestion of 1000 mg of chlorogenic acid, however, the area under the curve at the end of the test, or the total amount of insulin and blood sugar, did not vary significantly from the control subjects.  Chlorogenic acid therefore appears to delay, but not prevent, glucose absorption according to this study.

The results of a 2007 article, however, which is discussed in more detail below under ‘reduced body mass and fat” are at variance with this, found that glucose absorption was reduced by 6.9% following a similar dose of chlorogenic acid within a large cup of instant coffee.  Also supporting this effect are laboratory animal studies with rodents which have found that supplementing the rats’ meals with chlorogenic acid did significantly lower the area under the curve for blood glucose and insulin after the meal.

One way in which chlorogenic acid might reduce the rate and/or the total amount of carbohydrates absorbed from food is by its action as an alpha-glucosidase inhibitor.  Alpha-glucosidase is an enzyme which breaks starches down into glucose, so reducing the rate at which it functions can reduce the amount of carbohydrate which winds up in the bloodstream as glucose.  

Reduced production of glucose in the liver

Chlorogenic acid has also been found in vitro to inhibit the liver enzyme glucose-6-phosphatase which plays a critical role in the production of glucose in the liver.  In laboratory studies of human liver cells in petri dishes, a 1 mM solution of chlorogenic acid was shown to reduce the activity of glucose-6-phosphatase by 40%.  It is likely that chlorogenic acid reduces the amount of glucose produced by the liver in humans, although so far experiments have not been able to demonstrate a reduction in the rate of glucose produced by liver cells in petri dishes, nor in liver perfusion experiments.  Infusing chlorogenic acid via intravenous infusion did not result in a reduction in blood glucose levels, indicating that the levels of chlorogenic acid obtainable in vivo are not great enough to reproduce the effects observed in vitro.

Increased uptake of glucose in muscle tissue

Chlorogenic acid can increase the rate at which muscles use glucose in two ways. It can directly stimulate the enzyme AMPK, specifically the A2 subunit, which performs a whole host of actions in the body, one of which is stimulating muscle tissue to take up glucose for energy, independent of insulin.  It is possible that it is actually the caffeic acid metabolite of chlorogenic acid which does this as, in laboratory studies at least, chlorogenic acid is not known to directly stimulate AMPK through increased phosphorylation.  Phosphorylation occurs when a phosphate group is added to a protein such as an enzyme (or some other organic molecule), which in the case of protein enzymes acts as an on/off switch for the enzyme, causing it to function or not.

The other way chlorogenic acid can increase the utilisation of blood glucose by muscle is by stimulating the glucose transporter type 4 (GLUT4) protein which works with insulin to transport glucose into the cells.  The GLUT4 protein is stimulated through  phosphorylation of the AKT2 type of protein kinase B (PKB).

Reduced risk of type II diabetes

People who drink a significant amount of coffee have less of a risk of developing type II diabetes than non-coffee drinkers.  As caffeine worsens insulin sensitivity, this effect has been attributed to chlorogenic acid.  Generally, the more coffee that is consumed over a long period of time, the less the risk of developing diabetes.

Protection against Alzheimer’s disease, nerve degeneration

Neurodegenerative disorders including Alzheimer’s disease are strongly associated with oxidative stress to nerve cells, called neurons.  This oxidative damage is caused by reactive oxygen species including hydrogen peroxide.  Population studies have linked moderate coffee consumption with a reduced risk of neurodegenerative diseases and laboratory studies have begun to confirm that chlorogenic acid is one of the agents responsible for this protective effect, although caffeine is also considered likely to have a protective effect.

Chlorogenic acid protects neurons from hydrogen peroxide-induced stress through upregulating the antioxidant enzyme NADPH:quinine oxidoreductase 1 (NQO1).  Other studies have indicated that chlorogenic acid may also work to preserve dopaminergic neurons by suppressing inflammation in the neurons.

Reduced risk of liver disease

The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including cirrhosis of the liver and hepatocellular carcinoma (liver cancer) as well as gallstones.

Reduced body mass and fat

A small study of 30 overweight or obese subjects aged 18-44 found that those who drank instant coffee enriched with chlorogenic acid over a period of 12 weeks, lost an average of 5.4 kg as opposed to 1.7 kg in the control group.  This study attributed this effect to a 6.9% reduction in the amount of glucose absorbed from the diet, which they noted from an initial study they performed on the effects of a single dose of instant coffee (10 grams) which contained 909 mg of chlorogenic acid. This ‘single dose of coffee’ is equivalent to about 5 standard cups of instant coffee, which generally contain 2 grams of instant coffee powder.

Studies in mice have found that chlorogenic acid had a strong effect at lowering body mass, fat, insulin and leptin levels in obese mice, when it was added to their diets at a rate 0.02% by weight, meaning that for every kilogram of food they consumed they were given about 200 milligrams of chlorogenic acid.   They concluded that both caffeic acid and chlorogenic acid improve body weight, lipid metabolism and obesity-related hormones levels in high-fat fed mice with chlorogenic acid appearing to be the more potent of the two for body weight reduction and regulation of lipid metabolism.

A study published in May 2013, however, directly contradicted this, finding that male mice who were fed a high-fat diet which was 0.1% chlorogenic acid by weight (1 gram per kilogram of food) had a greater incidence of insulin resistance and fatty liver than mice who were merely fed a high-fat diet without the supplement.

We are not mice, and this is only one negative study in a sea of positive ones.  The results may not be relevant, or they may not be reproducible, however, research into the effects of chlorogenic acid is in its infancy and caution should be practised when deciding whether or not to supplement one’s diet.

Increase fat-burning and inhibit new fat cells forming

Some studies have suggested that chlorogenic acid may be able to induce body fat loss by increasing the rate at which calories are converted into heat.  This process is called thermogenesis.  Chlorogenic acid may increase thermogenesis by acting as a peroxisome proliferator-activated receptor alpha or PPARa agonist as do the fibrate class of drugs which are used to treat disorders of cholesterol and triglyceride levels.

In vitro studies have indicated that chlorogenic acid may also reduce the proliferation of new fat cells through its anti-oxidant effects.

Mild laxative

Chlorogenic acid is likely responsible for at least part of the laxative effect of prunes, stone fruit and coffee.

Lower blood pressure

Chlorogenic acid has also been found to lower blood pressure.  The effect on healthy volunteers who were given  200 mg of chlorogenic acid averaged a 2.5 mmHg reduction in systolic blood pressure and 1.5 mmHg in diastolic blood pressure.  Another study found that in people with mild hypertension just 140 mg per day of chlorogenic acid reduced blood pressure safely, without any side effects, by around 5 mmHg systolic and 15 mmHg diastolic, but at this dose had no effect on body mass index nor pulse rate.  The effect wore off 2 weeks after chlorogenic acid supplementation ceased.

Blood pressure is measured systolic/diastolic with a normal blood pressure considered to be in the vicinity of 120/80.

Stimulant

Chlorogenic acid has a weak psychostimulant effect, with animal studies in rats estimating the effect to be around one third as strong as the effect from caffeine.

Improve mood and cognitive abilities

A 2012 study in healthy elderly participants found that decaffeinated coffee with a higher concentration of chlorogenic acids (521 mg) improved their mood and ability to perform a battery of cognitive tasks in comparison with ordinary decaffeinated coffee which contained only 224 mg chlorogenic acids.

Does chlorogenic acid react with metformin?
Chlorogenic acid has been found to potentiate, or increase, the action of some anti-diabetic drugs including metformin and thiazolidinedione (THZ) drugs such as Avandia and Actos, increasing the rate of glucose uptake into fat cells by 6-7 times that of the drugs by themselves.  It may also alleviate some of the side effects and secondary complications which can occur as a result of these drugs, through increasing the expression of the PPARy receptor protein.  These phytochemicals were able to reduce the expressions of two genes which are affected by the drugs, the fatty acid synthase gene and the HMG CoA reductase gene.
Chlorogenic acid vs. coffee

Coffee is a complex chemical elixir which contains over a thousand different chemicals, including carbohydrates, lipids, vitamins, minerals, alkaloids, nitrogenous compounds and phenolic compounds.  Research to date has focused on just a handful.  The chemicals in coffee do not act independently within the body, they interact with each other in innumerable different ways, most of which we are yet to discover.  This may mean that all of the compounds in coffee work better for weight loss and glucose metabolism than just isolating certain compounds out, or the reverse may be true.

Unfiltered coffee contains the chemical compounds cafestol and kahweol which exert a negative effect on cholesterol, increasing LDL cholesterol and reducing HDL cholesterol.  As women with PCOS tend to have a poor cholesterol balance, this may be a good reason to either stick to filtered coffee or use a chlorogenic acid supplement.

Before you increase your coffee consumption in the interests of your health, it is worth noting two points: caffeine has a detrimental effect on insulin sensitivity and most of the chlorogenic acid in coffee is destroyed during the roasting process and a compound produced during the roasting process, called hydroxyhydroquinone or HHQ, can inhibit the actions of what little chlorogenic acid is left, in vivo.  

What is the effect of coffee on health?

Caffeine is known to increase the metabolism of humans as well as the rate at which fat is burned in normal weight individuals.  In lean people, it increases thermogenesis by around 7.5 %, in obese individuals by around 5 %.  It increases mood and mental alertness, but has also been strongly linked to an increased risk of acute myocardial infarction (heart attack), particularly in people who have a reduced ability to metabolise it, which results in the caffeine floating around the body for longer, exerting its effects for longer.

No differences in lipid (fat) metabolism, lipolysis (the rate at which fat is metabolised), or any other direct anti-obesity mechanism has yet been identified which is isolated to chlorogenic acid by itself rather than to the combination of chlorogenic acid (and possibly other polyphenols) in conjunction with the caffeine present in coffee as a whole food rather than a supplemental form of isolated constituents.

For adults consuming moderate amounts of coffee (3-4 cups per day providing 300-400 mg per day of caffeine), there is little evidence of health risks and some evidence of health benefits.  It has been well established through epidemiological (population) studies and animal studies that moderate coffee consumption is associated with a reduction in body mass and fat mass as well as a reduced risk of developing type II diabetes through an improvement in glucose tolerance.  It appears that the anti-diabetic effect of chlorogenic acid is greater than the pro-diabetic effect of caffeine when consumed in the ratios and amounts found in typical coffee beverages.

What is not clear is whether the effect on weight is due to caffeine, chlorogenic acids, other polyphenols or phytochemical compounds in the coffee or behavioural factors in coffee drinkers as opposed to coffee abstainers.  It has been suggested that the reduction in body and fat mass may be due to caloric displacement, i.e. drinking a calorie-free or low-calorie beverage such as coffee, instead of a higher-calorie food or beverage such as sugary drinks or a snack.  Some studies, however, have found that the link between coffee intake and reduced body mass extends to decaffeinated coffee beverages, which would imply that caffeine is not solely responsible for the effect and that other polyphenols, such as chlorogenic acid exert an effect on body weight.

It is also possible, however, that the effect is due to an improvement in glucose tolerance (from the chlorogenic acid) which results in less insulin being produced, resulting in less hunger being experienced leading to less food being consumed and less glucose being stored as fat as a result of the action of insulin.  Lower insulin levels result in less glucose being stored as fat.

How much chlorogenic acid is in coffee?

It is estimated that an ‘average’ coffee drinker probably consumes around 500 – 1000 mg of chlorogenic acid per day with one litre of  ”coffee” providing between 500 and 800 mg of chlorogenic acid and that this is sufficient to provide a long-term preventative effect against the development of diabetes.  There is, however, a huge variability in the amount of chlorogenic acid in a cup of coffee depending upon factors such as the type of coffee bean used, the quality of the bean, the extraction method and the volume.

There is no ‘standard’ cup of coffee and this makes estimating the amount of chlorogenic acid obtained from food very difficult.  A 2003 study published in the American Journal of Clinical Nutrition found that the average amount of chlorogenic acid found in instant coffee (both caffeinated and decaffeinated) was in the range of 30-40 mg/g.  A teaspoon of instant coffee is about 2 grams as are the pre-measured paper tubes of instant coffee.  This would imply that a typical cup of instant coffee would contain 60-80 mg of chlorogenic acid.A 2012 study published by the Royal Society of Chemistry journal Food and Function found that amongst 20 commercial espresso samples purchased in Glasgow, caffeine content varied between 51 mg and 322mg and the chlorogenic acid content ranged from 24 to 422 mg.  Starbucks coffee was noted to contain the least chlorogenic acid by a factor of 17 and the least caffeine by a factor of 4.  The ratio of chlorogenic acid to caffeine also varied considerably from 0.47 to 1.94 with starbucks providing twice as much caffeine as chlorogenic acid and Patisserie Francoise actually providing more chlorogenic acid (422 mg) than caffeine (322 mg).

For coffee afficionados

Coffee from coffea arabica beans makes up around 70% of worldwide coffee consumption with the remaining 30% composed of the more bitter variety coffea canephora, more commonly known as robusta.   Robusta coffee beans contain almost twice as much caffeine as do arabica beans, though some studies have also found that they contain twice as much chlorogenic acid and other polyphenol antioxidants.  This is likely only important to companies extracting the chlorogenic acid and refining it as other studies have found that a more beneficial chlorogenic acid to caffeine ratio in espresso is obtained from arabica beans.

During roasting, the beans are heated to 200-250 °C, and the roasting time can range from 45 seconds to 25 minutes, the optimum time being between 1.5 and 6 minutes, depending upon the degree of roasting required (light, medium, or dark).  During the roasting process, complex chemical changes take place in the coffee beans, many as a result of the Maillard or browning reaction.  Some antioxidants increase at light to medium roasting, whilst the amount of chlorogenic acid decreases.  Light roasting results in around a 19% reduction in the amount of chlorogenic acid, whilst medium roasting results in around a 45% decrease compared to the amount found in unroasted green coffee beans.

A high roasting temperature for a shorter time results in slightly less degradation of chlorogenic acids with 11 – 13.3% chlorogenic acids remaining as opposed to only 6.8 – 8 % for beans roasted at a lower temperature for a longer time.  Coffee extract from unwashed beans has a higher chlorogenic acid content (14.6 mg/ml) compared to washed beans (11.3 mg/ml) both before and after roasting when it reduces to between 1-1.5 mg /ml.  Caffeine content is not significantly affected by washing the beans.

What is the healthiest coffee?

In summary, if you are sufficiently entranced by your coffee to buy it from a boutique provider where you can select these options, the better option is for a 100% arabica, unwashed bean roasted at a high temperature for a short amount of time.  This will give you the best chlorogenic acid to caffeine ratio available from the various processing methods.  An even better option would be if you can obtain this coffee in a decaffeinated version using the Swiss-water decaffeination method, which does not involve the use of harmful solvents to remove the caffeine.

Potential side-effects

It was hypothesized in the 1960′s that chlorogenic acid was a chemical sensitizer, responsible for causing respiratory allergies to certain plant materials containing chlorogenic acid in humans.  Some experiments on animals using fairly aggressive techniques, did cause severe allergic reactions after the material was injected into the animals, both to sensitise them and again to elicit the allergic response.

Coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine levels.  Chlorogenic acid has also been associated with increased levels of the protein amino acid homocysteine.  Increased homocysteine levels are linked to an increase in the risk of cardiovascular disease, however, it has not been proven that reducing elevated homocysteine improves cardiovascular outcomes for people.  A 2001 study found that 2.5 g of chlorogenic acid increased homocysteine levels in humans by 12%, 4.5 grams of black tea powder, roughly the equivalent to 2 litres of strong black tea, increased homocysteine levels by 11% when compared with placebo, 4 – 5 hours after consumption.  By 20 hours, this increase had reduced to only 4% for chlorogenic acid and 5% for black tea.  Elevated homocysteine levels can also be caused by deficiencies in the B vitamins pyridoxine (B6), folate (vitamin B9) and cobalomin (B12).  Women with PCOS tend to be at greater risk of B vitamin deficiencies in general and if they have taken the insulin-sensitizing drug metformin, B12 deficiencies in particular.  It would therefore appear to be wise to have your homocysteine levels checked regularly if you choose to take chlorogenic acid supplements and to take a B vitamin complex as these three B vitamins have been found to lower homocysteine, as has the enzyme betaine.

Chlorogenic acid and caffeic acid were once thought to be capable of inducing vitamin B1 deficiency, however, this hypothesis was disproven in the early 1980′s.  It can however, reduce the absorption of zinc and iron from the diet.

Chemistry
Chlorogenic Acid from Green Coffee Bean Extract

In pure chemical terms, chlorogenic acid is the quinic acid conjugate of caffeic acid, the ester formed when the two are joined.  The term chlorogenic acid, however, is actually used to describe a group of chlorogenic acids, including quinic acid combined with either caffeic acid, ferulic acid or p-coumaric acid, which are a family of related esters of hydroxycinnamic acids.  The name chlorogenic acid actually comes from the Greek word for light green because of the colour the acids turn when they oxidise.  A good example of this is in potatoes.

Coffee contains a family of conjugated hydroxycinnamates collectively referred to as chlorogenic acids. The main chlorogenic acids are 5-Ocaffeoylquinic acid (5-CQA) and its isomers 3-O-caffeoylquinic acid (3-CQA) and 4-O-caffeoylquinic acid (4-CQA) and together these account for 80% of the total chlorogenic acids.

Very little of the chlorogenic acid which is ingested appears to be absorbed into the bloodstream, with chlorogenic acid remaining stable throughout its journey through the stomach and small intestine with only one third being absorbed there.  The majority appears to remain intact in the intestines where it can hinder the absorption of carbohydrates, zinc and non-haem iron, or iron from vegetable sources.  When chlorogenic acid reaches the caecum, or the junction between the small intestine and the colon, the microflora present there break the bond between the quinic acid and caffeic acid molecules, which can then be absorbed into the blood stream from the colon.

About half of ingested chlorogenic acid is metabolised into hippuric acid, with the possibility that one molecule of chlorogenic acid may be able to produce two molecules of hippuric acid, if both the caffeic acid and quinic acid moieties are metabolised into hippuric acid.  Hippuric acid is sold under the brand name Hiprex as a urinary antiseptic for the treatment of urinary tract infections (in conjunction with other ingredients).  It has a mild antiseptic effect in the urine and keeps the pH more acidic.

In Summary

Research into chlorogenic acid and its effects on obesity and insulin resistance is just beginning.  Some results are very positive, others more neutral and some indicate the possibility of negative effects under some circumstances.  Chlorogenic acid as a supplement, or coffee as part of a balanced diet, may provide some beneficial effects in relation to weight loss and glucose tolerance, through a ‘carb-blocking’ action, reducing the amount of carbohydrate that is absorbed in the stomach and intestines, increasing the amount of glucose used by the muscles and possibly reducing the amount of glucose produced by the liver.

Until the research is more conclusive, however, proceed with caution if you choose to take supplemental chlorogenic acid for weight loss or improved glucose tolerance and take a B-vitamin complex to protect against potential homocysteine increases and monitor your iron and folate levels to ensure you are getting an adequate amount of each.

At the very least, measure your weight before you start taking it, then again after one month.  If appropriate test your blood sugar levels regularly before and throughout, or have an HbA1c or glucose tolerance test, before and after.

For what it is worth, I have been taking 1-2 grams of chlorogenic acid per day, in the form of Green Coffee Bean Extract, standardised to contain 50% chlorogenic acid.  I’ve been taking it for over a year now and have noticed an improvement in blood glucose levels, though they were already within the normal range to begin with and the restoration of my menstrual cycle, which had disappeared for a year after taking metformin for two months.  I have also lost about 7 kilograms.

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USDA Agricultural Research Service Germplasm Resource Information Network http://www.ars-grin.gov/cgi-bin/duke/chemical.pl?CHLOROGENICACID
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3 comments to Chlorogenic Acid, Green Coffee Bean Extract and Coffee

  • This sounds interesting. As you stated, it’s early days. I’ve read somewhere (!) that drinking coffee negates the effects of d chiro inositol. Thoughts?

  • My PCOS Info

    Hi Merry,

    Thank you for asking this question, I’ve been meaning to do a post on it for years. It’s a commonly repeated myth that coffee or more specifically caffeine somehow ‘kills’ inositol, however, this is not correct. Caffeine does interact with inositol receptors in the body, but not to such a degree that it can cause any problems or deficiencies. That being said, it would be logical not to take them together and it is worth taking into consideration the effect of caffeine on insulin sensitivity: caffeine impairs insulin sensitivity by 15%. There are supplements available that provide just the chlorogenic acids without the caffeine, some are even tailored towards PCOS.

    Caffeine is capable of inhibiting the release of calcium via a specific type of inositol receptor (IP3) present in the cells of the body, however, according to more recent research in the February 2010 issue of the journal Cancer Research, caffeine does not actually affect the way inositol binds to these receptors anyway, which was probably the shaky ground upon which this weed first grew.

    I really would love to do a whole post on this one day and if I find the time I will!

    Kang SS, Han KS, Ku BM, Lee YK, Hong J, Shin HY, Almonte AG, Woo DH, Brat DJ, Hwang EM…. (2010) Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival. Cancer research, 70(3), 1173-83. PMID: 20103623

    Keijzers GB, De Galan BE, Tack CJ, & Smits P. (2002) Caffeine can decrease insulin sensitivity in humans. Diabetes care, 25(2), 364-9. PMID: 11815511

  • Ian Papatu

    This is really great information for those of us who need to know power of green coffee bean extract on our weight management. Excellent!

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