Life Extension Magazine 2011
Are We All Pre-Diabetic?
By Kirk Stokel
Life Extension Magazine 2011
By Kirk Stokel
Green Coffee Extract Improves Glucose Control
Green coffee bean extract found in unroasted coffee beans, once purified and standardized, produces high levels of chlorogenic acid and other beneficial polyphenols that can suppress excess blood glucose levels.
The research findings on the impact of chlorogenic acid on blood sugar are impressive. For starters, a team of Japanese researchers recorded a 43% drop in blood sugar levels after administering green coffee bean extract to mice after a heavy meal.24
Human clinical trials support the role of chlorogenic acid-rich green coffee bean extract in promoting healthy blood sugar control and reducing disease risk.
Aware of the crucial importance of controlling after-meal blood sugar spikes, scientists conducted a study among 56 healthy volunteers, challenging them with an oral glucose tolerance test before and after a supplemental dose of green coffee extract. The oral glucose tolerance test is a standardized way of measuring a person's after-meal blood sugar response.
In subjects not taking green coffee bean extract, the oral glucose tolerance test showed the expected rise of blood sugar to an average of 144 mg/dL after a 30 minute period. But in subjects who had taken 200 mg of the green coffee bean extract, that sugar spike was significantly reduced, to just 124 mg/dL—a 14% decrease1 (See figure 1).
That impressive difference was sustained throughout the two-hour study period at a dose as low as 200 mg of green coffee bean extract. Subjects had a mean 19% reduction of blood sugar at one hour, and a 22% reduction (glucose down to just 89 mg/dL) at two hours, compared to each patient's own untreated levels. In other words, the amount of time subjects had glucose levels in the dangerous range was sharply curtailed by the green coffee bean extract1 (See figures 2 and 3).
To state this differently, when subjects did not take the green coffee bean extract, their oral glucose tolerance reading after two hours showed blood sugar of 115 mg/dL—a higher-than-desirable level. In response to a modest dose of 200 mg of green coffee bean extract, two-hour blood sugar levels dropped to only 89 mg/dL1 (See figure 3).
For most aging individuals, even after eating nothing for eight to twelve hours, it is challenging to achieve a "fasting" glucose reading as low as 89 mg/dL. Yet when these study subjects took 200 mg of green coffee bean extract, their glucose levels dropped to 89 mg/dL just two hours after drinking a pure glucose solution. The high-dose glucose drink used in standard oral glucose tolerance tests spikes blood sugar more than typical meals.
When a higher dose (400 mg) of green coffee bean extract was supplemented before an oral glucose challenge test there was an even greater average reduction in blood sugar—up to nearly 28% at one hour!1
How Green Coffee Bean Extract Suppresses Glucose Elevation
Scientists have discovered that chlorogenic acid found abundantly in green coffee bean extract inhibits the enzyme glucose-6-phosphatase that triggers new glucose formation and glucose release by the liver.25,26 As discussed earlier, glucose-6-phosphatase is involved in dangerous after-meal spikes in blood sugar.27
Another means by which chlorogenic acid acts to suppress after-meal glucose surges is by inhibiting alpha-glucosidase. This intestinal enzyme breaks apart complex sugars and enhances their absorption into the blood.28 Slowing the absorption of common sugars (including sucrose) limits after-meal glucose spikes.29
In yet another significant mechanism, chlorogenic acid increases the signal protein for insulin receptors in liver cells.30 That has the effect of increasing insulin sensitivity, which in turn drives down blood sugar levels.
Chlorogenic acid-rich plant extracts have been shown to reduce fasting blood glucose values by more than 15% in diabetic patients with poor response to medication.31 A similar effect was seen in healthy volunteers, whose intestinal absorption of glucose was reduced following a chlorogenic acid-enriched coffee drink.32
When a chlorogenic acid supplement of 1 gram was given before meals, glucose levels were reduced by 13 mg/dL, just 15 minutes after an oral glucose challenge, demonstrating its ability to rapidly lower the after-meal blood sugar spike in humans.33
In a clinical trial, researchers gave different dosages of green coffee bean extract, standardized for chlorogenic acid, to 56 people. Thirty-five minutes later, they gave the participants 100 grams of glucose in an oral glucose challenge test. Blood sugar levels dropped by an increasingly greater amount as the test dosage of green coffee bean extract was raised, from 200 mg up to 400 mg. At the 400 mg dosage, there was a full 24% decrease in blood sugar—just 30 minutes after glucose ingestion.1
This means that if you had a dangerous after-meal glucose reading of 160 mg/dL, green coffee bean extract would slash it to 121 mg/dL.
These findings are in line with supportive data demonstrating green coffee bean extract's numerous blood sugar-reducing mechanisms of action.
Other experimental models reveal that chlorogenic acid favorably modulates gene expression to enhance the activity of liver cells and increase levels of the hormone adiponectin, which enhances insulin sensitivity and exerts anti-inflammatory, anti-diabetic, and anti-atherogenic effects.34
The need to redefine diabetes is critical because risk of premature death and disease rises sharply with fasting blood sugar greater than 85 mg/dL.
Furthermore, the insidious impact of after-meal blood sugar spikes goes largely undetected, exposing the vast majority of people to accelerated disease risk.
Behind this danger is the little-appreciated role of glucose-6-phosphatase in creating and releasing additional glucose into the blood. This enzyme, which helps regulate blood sugar when you're young, can inappropriately trigger a dangerous after-meal surge of blood sugar as you age.
Avant-garde scientists have identified a breakthrough weapon to control these surges: green coffee bean extract. This natural ingredient contains a compound called chlorogenic acid shown to target glucose-6-phosphatase and blunt post-consumption blood sugar levels by up to 32%.
A consistent finding in those who restrict their calorie intake is markedly lower blood glucose levels. Longevity enthusiasts can now benefit from a novel yet natural green coffee bean extract to combat internal processes that cause dangerous elevations in blood glucose.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
1. Nagendran MV. Effect of green coffee bean extract (GCE), High in Chlorogenic Acids, on Glucose Metabolism. Poster presentation number: 45-LB-P. Obesity 2011, the 29th Annual Scientific Meeting of the Obesity Society. Orlando, Florida. October 1-5, 2011.
2. Nichols GA, Hillier TA, Brown JB. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis. Am J Med. 2008 Jun;121(6):519-24.
3. Kato M, Noda M, Suga H, Matsumoto M, Kanazawa Y. Fasting plasma glucose and incidence of diabetes—implication for the threshold for impaired fasting glucose: results from the population-based Omiya MA cohort study. J Atheroscler Thromb. 2009;16(6):857-61.
4. Available at: http://diabetes.niddk.nih.gov/dm/pubs/diagnosis/#diagnosis. Accessed August 15, 2011.
5. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe. Lancet. 1999 Aug 21;354(9179):617-21.
6. Nakagami T. Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin. Diabetologia. 2004 Mar;47(3):385-94.
7. Miura K, Kitahara Y, Yamagishi S. Combination therapy with nateglinide and vildagliptin improves postprandial metabolic derangements in Zucker fatty rats. Horm Metab Res. 2010 Sep;42(10):731-5.
8. Monnier L, Colette C. Glycemic variability: should we and can we prevent it? Diabetes Care. 2008 Feb;31 Suppl 2:S150-4.
9. Monnier L, Colette C, Owens DR. Glycemic variability: the third component of the dysglycemia in diabetes. Is it important? How to measure it? J Diabetes Sci Technol. 2008 Nov;2(6):1094-100.
10. Triggle CR. The early effects of elevated glucose on endothelial function as a target in the treatment of type 2 diabetes. Timely Top Med Cardiovasc Dis. 2008;12:E3
11. Gerstein HC, Pais P, Pogue J, Yusuf S. Relationship of glucose and insulin levels to the risk of myocardial infarction: a case-control study. J Am Coll Cardiol. 1999 Mar;33(3):612-9.
12. Lin HJ, Lee BC, Ho YL, et al. Postprandial glucose improves the risk prediction of cardiovascular death beyond the metabolic syndrome in the nondiabetic population. Diabetes Care. 2009 Sep;32(9):1721-6.
13. Yu PC, Bosnyak Z, Ceriello A. The importance of glycated haemoglobin (HbA(1c)) and postprandial glucose (PPG) control on cardiovascular outcomes in patients with type 2 diabetes. Diabetes Res Clin Pract. 2010 Jul;89(1):1-9.
14. Batty GD, Kivimäki M, Smith GD, Marmot MG, Shipley MJ. Post-challenge blood glucose concentration and stroke mortality rates in non-diabetic men in London: 38-year follow-up of the original Whitehall prospective cohort study. Diabetologia. 2008 July;51(7):1123-6.
15. Hemmerle H, Burger HJ, Below P, et al. Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepatic glucose-6-phosphate translocase. J Med Chem. 1997 Jan 17;40(2):137-45.
16. Arion WJ, Canfield WK, Ramos FC, et al. Chlorogenic acid and hydroxynitrobenzaldehyde: new inhibitors of hepatic glucose 6-phosphatase. Arch Biochem Biophys. 1997 Mar 15;339(2):315-22.
17. Rizza RA. Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy. Diabetes. 2010 Nov;59(11):2697-707.
18. Henry-Vitrac C, Ibarra A, Roller M, Merillon JM, Vitrac X. Contribution of chlorogenic acids to the inhibition of human hepatic glucose-6-phosphatase activity in vitro by Svetol, a standardized decaffeinated green coffee extract. J Agric Food Chem. 2010 Apr 14;58(7):4141-4.
19. Salazar-Martinez E, Willett WC, Ascherio A, et al. Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med. 2004 Jan 6;140(1):1-8.
20. Pereira MA, Parker ED, Folsom AR. Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28,812 postmenopausal women. Arch Intern Med. 2006 Jun 26;166(12):1311-6.
21. Johnston KL, Clifford MN, Morgan LM. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr. 2003 Oct;78(4):728-33.
22. Bidel S, Hu G, Sundvall J, Kaprio J, Tuomilehto J. Effects of coffee consumption on glucose tolerance, serum glucose and insulin levels--a cross-sectional analysis. Horm Metab Res. 2006 Jan;38(1):38-43.
23. van Dam RM, Feskens EJM. Coffee consumption and risk of type 2 diabetes mellitus. Lancet. 2002 Nov 9;360(9344):1477-8.
24. Murase T, Misawa K, Minegishi Y, Aoki M, Ominami H, Suzuki Y, Shibuya Y, Hase T. Coffee polyphenols suppress diet-induced body fat accumulation by downregulating SREBP-1c and related molecules in C57BL/6J mice. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E122-33.
25. Henry-Vitrac C, Ibarra A, Roller M, Merillon JM, Vitrac X. Contribution of chlorogenic acids to the inhibition of human hepatic glucose-6-phosphatase activity in vitro by Svetol, a standardized decaffeinated green coffee extract. J Agric Food Chem. 2010 Apr 14;58(7):4141-4.
26. Andrade-Cetto A, Vazquez RC. Gluconeogenesis inhibition and phytochemical composition of two Cecropia species. J Ethnopharmacol. 2010 Jul 6;130(1):93-7.
27. Bassoli BK, Cassolla P, Borba-Murad GR, et al. Chlorogenic acid reduces the plasma glucose peak in the oral glucose tolerance test: effects on hepatic glucose release and glycaemia. Cell Biochem Funct. 2008 Apr;26(3):320-8.
28. Ishikawa A, Yamashita H, Hiemori M, et al. Characterization of inhibitors of postprandial hyperglycemia from the leaves of Nerium indicum. J Nutr Sci Vitaminol (Tokyo). 2007 Apr;53(2):166-73.
29. Alonso-Castro AJ, Miranda-Torres AC, Gonzalez-Chavez MM, Salazar-Olivo LA. Cecropia obtusifolia Bertol and its active compound, chlorogenic acid, stimulate 2-NBDglucose uptake in both insulin-sensitive and insulin-resistant 3T3 adipocytes. J Ethnopharmacol. 2008 Dec 8;120(3):458-64.
30. Rodriguez de Sotillo DV, Hadley M, Sotillo JE. Insulin receptor exon 11+/- is expressed in Zucker (fa/fa) rats, and chlorogenic acid modifies their plasma insulin and liver protein and DNA. J Nutr Biochem. 2006 Jan;17(1):63-71.
31. Herrera-Arellano A, Aguilar-Santamaria L, Garcia-Hernandez B, Nicasio-Torres P, Tortoriello J. Clinical trial of Cecropia obtusifolia and Marrubium vulgare leaf extracts on blood glucose and serum lipids in type 2 diabetics. Phytomedicine. 2004 Nov;11(7-8):561-6.
32. Thom E. The effect of chlorogenic acid enriched coffee on glucose absorption in healthy volunteers and its effect on body mass when used long-term in overweight and obese people. J Int Med Res. 2007 Nov-Dec;35(6):900-8.
33. van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. Diabetes Care. 2009 Jun;32(6):1023-5.
34. Zhang LT, Chang CQ, Liu Y, Chen ZM. Effect of chlorogenic acid on disordered glucose and lipid metabolism in db/db mice and its mechanism. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2011 Jun;33(3):281-6.
35. Hemminki K, Li X, Sundquist J, Sundquist K. Risk of cancer following hospitalization for type 2 diabetes. The Oncologist. 2010;15(6):548-55. Epub 2010 May 17.
36. Czyzyk A, Szczepanik Z. Diabetes mellitus and cancer. Eur J Intern Med. 2000 Oct;11(5):245-52.
37. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009 Dec;16(4):1103-23.
38. Martin-Castillo B, Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. Metformin and cancer: doses, mechanisms and the dandelion and hormetic phenomena. Cell Cycle. 2010 Mar 21;9(6):1057-64.
39. Cust AE, Kaaks R, Friedenreich C, Bonnet F, et al. Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition EPIC. Endocr Relat Cancer. 2007 Sep;14(3):755-67.
40. Rosato V, Tavani A, Bosetti C, et al. Metabolic syndrome and pancreatic cancer risk: a case-control study in Italy and meta-analysis. Metabolism. 2011 May 5.
41. Schoen RE, Tangen CM, Kuller LH, et al. Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst. 1999 Jul 7;91(13):1147-54.
42. Aleksandrova K, Boeing H, Jenab M, et al. Metabolic syndrome and risks of colon and rectal cancer: the European Prospective Investigation into Cancer and Nutrition Study. Cancer Prev Res (Phila). 2011 Jun 22.
43. Healy L, Howard J, Ryan A, et al. Metabolic syndrome and leptin are associated with adverse pathological features in male colorectal cancer patients. Colorectal Dis. 2011 Jan 20.
44. Pan WH, Cedres LB, Liu K, et al. Relationships of clinical diabetes and symptomatic hyperglycaemia to risk of coronary heart disease mortality in men and women. Am J Epidemiol. 1986;123:504-16.
45. Wilson PWF, Cupples LA, Kannel WB. Is hyperglycaemia associated with cardiovascular disease? The Framingham Study. Am Heart J. 1991 Feb;121(2 Pt 1):586-90.
46. de Vegt F, Dekker JM, Ruhe HG, et al. Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn study. Diabetologia. 1999 Aug;42(8):926-31.
47. Saydah SH, Miret M, Sung J, Varas C, Gause D, Brancati FL. Post-challenge hyperglycemia and mortality in a national sample of U.S. adults. Diabetes Care. 2001;24:1397-402.
48. Coutinho M, Gerstein H, Poque J, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events: a meta regression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999;22:233–40.
49. Donahue RP, Abbott RD, Reed DM, et al: Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program. Diabetes. 1987 Jun;36 (6):689-92.
50. Tali Cukierman-Yaffe T, Gerstein HC, Williamson JD. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care. 2009 Feb;32(2):221-6.
51. Sonnen JA, Larson EB, Brickell K. Different patterns of cerebral injury in dementia with or without diabetes. Arch Neurol. 2009 Mar;66(3):315-322.
52. Polhill TS, Saad S, Poronnik S, Fulcher GR, Pollock CR. Short-term peaks in glucose promote renal fibrogenesis independently of total glucose exposure. Am J Physiol Renal Physiol. 2004 Aug;287(2):F268-73.
53. Bash, LD, Selvin E, Steffes M, Coresh J, Astor BC. Poor glycemic control in diabetes and the risk of incident kidney disease even in the absence of albuminuria and retinopathy: atherosclerosis risk in communities (ARIC) study. Arch Intern Med. 2008 Dec 8/22;168(22):2440-7.
54. Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, De Fronzo RA, San Antonio metabolism study. Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Diabetologia 2004 Jan;47(1):31-9.
55. Available at: http://docnews.diabetesjournals.org/content/2/8/1.2.full. Accessed August 16, 2011.
56. Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology. 2003 Jan 14;60(1):108-11.
57. Hoffman-Snyder C; Smith BE; Ross MA; Hernandez J; Bosch EP. Value of the oral glucose tolerance test in the evaluation of chronic idiopathic axonal polyneuropathy. Arch Neurol. 2006 Aug;63(8):1075-9.
58. van Dam RM, Feskens EJ. Coffee consumption and risk of type 2 diabetes mellitus. Lancet. 2002 Nov 9;360(9344):1477-8.
59. Rosengren A, Dotevall A, Wilhelmsen L, Thelle D, Johansson S. Coffee and incidence of diabetes in Swedish women: a prospective 18-year follow-up study. J Intern Med. 2004 Jan;255(1):89-95.
60. Huxley R, Lee CM, Barzi F, et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med. 2009 Dec 14;169(22):2053-63.
61. Salazar-Martinez E, Willett WC, Ascherio A, et al. Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med. 2004 Jan 6;140(1):1-8.
62. Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr. 2011 Apr;51(4):363-73.
63. Granado-Serrano AB, Martin MA, Izquierdo-Pulido M, Goya L, Bravo L, Ramos S. Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. J Agric Food Chem. 2007 Mar 7;55(5):2020-7.
64. Kang NJ, Lee KW, Kim BH, et al. Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis. 2011 Jun;32(6):921-8.
65. Rakshit S, Mandal L, Pal BC, et al. Involvement of ROS in chlorogenic acid-induced apoptosis of Bcr-Abl+ CML cells. Biochem Pharmacol. 2010 Dec 1;80(11):1662-75.
66. Tai J, Cheung S, Chan E, Hasman D. Antiproliferation effect of commercially brewed coffees on human ovarian cancer cells in vitro. Nutr Cancer. 2010;62(8):1044-57.
67. Larsson SC, Virtamo J, Wolk A. Coffee consumption and risk of stroke in women. Stroke. 2011 Apr;42(4):908-12.
68. Panagiotakos DB, Pitsavos C, Chrysohoou C, Kokkinos P, Toutouzas P, Stefanadis C. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J Nutr. 2003 Oct;133(10):3228-32.
69. Zhang Y, Lee ET, Cowan LD, Fabsitz RR, Howard BV. Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: the Strong Heart Study. Nutr Metab Cardiovasc Dis. 2011 Jun;21(6):418-23.
70. Available at: http://www.ico.org/caffeine.asp. Accessed July 21, 2011.
71. Suzuki A, Fujii A, Yamamoto N, et al. Improvement of hypertension and vascular dysfunction by hydroxyhydroquinone-free coffee in a genetic model of hypertension. FEBS Lett. 2006 Apr 17;580(9):2317-22.
72. Yamaguchi T, Chikama A, Mori K, et al. Hydroxyhydroquinone-free coffee: a double-blind, randomized controlled dose-response study of blood pressure. Nutr Metab Cardiovasc Dis. 2008 Jul;18(6):408-14.