Blueberry Leaves Extract Lower Glucose

Human Clinical Study: Healthy Volunteers – Russian scientist Dr. M. Abidoff evaluated the Glucose lowering properties of blueberry leaves extract in double blind placebo controlled study at Moscow Center for Modern Medicine, Russian Ministry for National Defense Industries (Abidoff 1999, Abidoff-Farma), Russia.
According to this research the CA and HCA makes up as much as 18±2% of blueberry leaves extract. Seventy-five healthy volunteers age between 37-66 years were invited to participate in double -blind placebo-controlled five-week trial. Sixty days before beginning the drug phase of this trial, volunteers underwent a period of diet counseling and surveillance. Their dietary intakes were standardized to contain 55-60% % total calories from carbohydrates. At 3-week intervals throughout the study, volunteers were evaluated for fasting plasma glucose values. Standard food record analysis and a symptom questionnaire were also included at the laboratory intervention times.

After the initial dietary run-in phase, subjects were randomly assigned to receive 150mg of standardized blueberry leaves extract standardized or placebo, to be taken three times a day in 200 ml of water before meals. Results of this study revealed that there was significant change in blood glucose values for both groups of volunteers. The after meal blood glucose level increased from 102mg/dL±8md/dl (baseline) to 142mg/dL ±7mg/dL in placebo group. Those volunteers taking the blueberry leaves extract plasma glucose level increase from approximately 109mg/dL ± 9 mg /dL to 121mg/dL±6mg/dL. The results of this clinical trial indicate that the blueberry leaves extract possess physiologically significant glucose lowering property. According to Prof. Abidoff MD (1999) the glucose-lowering effect of blueberry leaves extract is due to unique properties of chlorogenic acid to inhibit the activity of G6P key enzyme in glycogenolysis and gluconeogenesis, although the direct inhibition of intestinal amylase– key enzyme in dietary carbohydrates absorption, by the blueberry leaves extract cannot be ruled out. In addition, results of Welsh et al. (1987) indicated that chlorogenic acid could inhibit the intestinal absorption of glucose.

Human Clinical Study: Diabetes Patients – In a second clinical trial the effect of blueberry leaves extract on plasma glucose level was studied in patients with Type II Diabetics (Abidoff 1999) Twenty-nine patients average age 50 years with type II diabetes were selected to participate in double -blind placebo-controlled 60 days trial. Sixty days before beginning the drug phase of clinical study, patients underwent a period of diet counseling and surveillance. Their dietary intakes were standardized to contain 40-45% total calories from carbohydrates. Patients in the study were asked to maintain their medications throughout the dietary and drug phase of the trial. On admission and at two-week intervals throughout the study, patients were evaluated for fasting glucose, triglycerides serum values. Food record analysis, body mass index, and a symptom questionnaire were also included at the laboratory intervention times. After this initial dietary run-in phase, subjects were randomly assigned to receive 200mg of standardized blueberry leaves extract powder in capsule

form or placebo, to be taken three times a day in 200 ml of water before meals. During the initial period of diet counseling there was no significant change in fasting blood glucose values for either of the groups. However, beginning with week 6 and continuing to the end of the trial, those individuals taking the blueberry leaves extract showed a

significant reduction in mean plasma glucose levels, from approximately 169 mg/dL to 136 mg/dL (p < 0.01). Furthermore, by the end of the clinical study, those taking the blueberry leaves extract showed a reduction triglyceride and LDL values from 179 ± 95 mg/dL to 130 ± 53 mg/L (p < 0.005) and 141 ± 47 mg/dL to 115 ± 34 mg/dL (p < 0.01) respectively. All patients tolerated well blueberry leaves extract at even 400mg/ three times a day (1200mg/day). Results of the clinical trial are confirmed well known and previously described phenomenon that the blueberry leaves extract possess antidiabetic properties. The use of blueberry leaves extract may provide a first line approach to the reduction of blood glucose in type II diabetes patients before other prescriptive avenues are employed. Improvement in total cholesterol and LDL level observed in various studies is possible due to protective role of caffeic and chlorogenic acids in LDL oxidation that was recently described in scientific literature.

Blueberry leaves extract: Science Re-discovers Another Ancient Truth of Folk Medicine. The long history of Blueberry leaves extract use in folk medicine and its growing popularity by the informed public is no longer a scientific mystery. Blueberry leaves extract is a safe, natural, potent source of critical chlorogenic and caffeic acids and has a long and venerable history and an even more promising future in the long-term care of diabetics everywhere. Once again, as has been the case with many other leading health supplements for the last two decades, science finally, reluctantly proves the efficacy of what it once not only ignored but openly denigrated! Yet what is profoundly fascinating is how often and how accurately the lore and legends of folk medicine so often proves to clinically accurate! When we delve deeper into the fast-growing, impressive body of this new research, we find in many cases the active compound(s) identified and responsible for an herb or food's traditional health benefits have been somehow empirically understood and used for the appropriate purpose in some form by many of our

 ancestors well into the past. Often such use occurred for thousands of years, in a variety of different cultures, spread over many continents. Although the folklore may have been local, taken as a whole the use of these natural medicines were regional, if not actually global. Ironically, modern researchers appear to be learning once again about the complex relationships between our bodies and these traditional food and medicine plants in a somewhat backward fashion. If researchers took a more humble and open-minded approach to the potential wisdom of traditional medicines like Blueberry leaves extract, they might accelerate their understanding and serve the mass acceptance and use of these very real "cultural treasures". Genuine scientific enthusiasm for this task would help set better standards for product formulation, consumer education, and public regulation, which, in turn, could help alleviate and even prevent the suffering of millions of people around the world from major chronic diseases such as diabetes in the future.

References:
Abraham SK, Sarma L, Kesavan PC (1993) Protective effects of chlorogenic acid, curcumin and beta- carotene against gammaradiation-induced in vivo chromosomal damage. Mutat Res; 303 (3):109-12
Arion WJ, Canfield WK, Ramos FC, Schindler PW. (1997) Chlorogenic acid and hydroxynitrobenzaldehyde: new inhibitor of hepatic glucose 6-phosphatase. Arch Biochem Biophys 15; 339(2):315-22
Arion WJ, Canfield WK, Ramos FC, Su ML, Burger HJ,

Hemmerle H, Schubert G, Below P, Herling AW Chlorogenic acid analogue S 3483: a potent competitive inhibitor of the hepatic and renal glucose-6-phosphatase systems. Arch Biochem Biophys 1998 15; 351 (2): 279-85
Azuma K, Ippoushi K, Nakayama M, Ito H, Higashio H, Terao J (2000) Absorption of Chlorogenic Acid and Caffeic Acid in Rats after Oral Administration J Agric Food Chem 20; 48 (11): 5496-5500
Bailey GS, Scanlan RA, Selivonchick DP, Williams DE (1991) Food toxicology. In "Encyclopedia of Human Biology," ed. R. Dulbecco, Vol. 3, pp. 671-681. Academic Press, New York.
Burke TR Jr, Fesen MR, Mazumder A, Wang J, Carothers
AM, Grunberger D, Driscoll J, Kohn K, Pommier Y (1995) Hydroxylated aromatic inhibitors of HIV-1 integrase. J Med Chem, 38 (21): 4171-8

Butland BK, Fehily AM, Elwood PC Diet, lung function, and lung function decline in a cohort of 2512 middle aged men. Thorax 2000; 55(2): 102-108
Chang WS, Wen PC, Chiang HC (1995) Structure-activity relationship of caffeic acid analogues on xanthine oxidase inhibition. Anticancer Res, 15(3): 703-7
Chang WS, Chang YH, Lu FJ, Chiang HC (1994) Inhibitory effects of phenolics on xanthine oxidase. Anticancer Res, 14(2A): 501-6

Cheng JT, Liu IM (2000) Stimulatory effect of caffeic acid on alpha1A-adrenoceptors to increase glucose uptake into cultured C2C12 cells. Naunyn Schmiedebergs Arch Pharmacol 362 (2): 122-7
Cho JY, Moon JH, Seong KY, Park KH (1998) Antimicrobial activity of 4-hydroxybenzoic acid and trans 4-hydroxycinnamic acid isolated and identified from rice hull. Biosci. Biotechnol Biochem 1998; 62 (11): 2273-6
Cignarella A, Nastasi M, Cavalli E, Puglisi L (1996) Novel lipidlowering properties of Vaccinium myrtillus L. leaves, a traditional antidiabetic treatment, in several models of rat dyslipidaemia: a comparison with ciprofibrate. Thromb Res 1; 84(5):311-22

Cornicelli JA, Trivedi BK (1999) 15-lipoxygenase and its inhibition: A novel therapeutic target for vascular disease. Current Pharmaceutical Design, 5: 11-12
Costantino L, Albasini A, Rastelli G, Benvenuti S (1992) Activity of polyphenolic crude extracts as scavengers of superoxide radicals and inhibitors of xanthine oxidase. Planta Med; 58(4): 342-4
Dhar K, Rosazza JP (2000) Purification and characterization of streptomyces griseus catechol O-methyltransferase. Appl Environ Microbiol; 66(11):4877-82
Dombrowicz E, Zadernowski R, Swiatek L (1991) Phenolic acids in leaves of Arctostaphylos uva ursi L., Vaccinium vitis idaea L. and Vaccinium myrtillus L Pharmazie; 46(9): 680-681
Feinmark SJ, Cornicelli JA (1997) Is there a role for 15-lipoxygenase in atherogenesis? Biochem Pharmacol 1; 54 (9): 953-9

Fernández MA, García MD, Sáenz MT (1996) Antibacterial activity of the phenolic acids fractions of Scrophularia frutescens and Scrophularia sambucifolia. J Ethnopharmacol, 53(1): 11-4
Folkers K, Langsjoen P, Willis R, Richardson P, Xia LJ, Ye CQ, Tamagawa H (1990) Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci U S A; 87(22): 8931-4
Fraisse D, Carnat A, Lamaison JL (1996) Polyphenolic composition of the leaf of bilberry Ann Pharm Fr, 54(6): 280-3

Hecht SS, Hoffman D (1988) Tobacco-specific nitrosamines, An important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis 9: 875-884.
Hemmele H, Burger HJ, Below P, Schubert G (1997) Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepatic glucose-6-phosphate translocase. J Med Chem 17; 40(2): 137-145
Hotchkiss JH (1989) Relative exposure to nitrite, nitrate, and Nnitroso compounds from endogenous and exogenous sources. In "Food Toxicology, A Perspective on the Relative Risks," ed. S.L. Taylor and R.A. Scanlan, pp. 57-100. Marcel Dekker, Inc., New York.
Hsu FL, Chen YC, Cheng JT (2000) Caffeic acid as active principle from the fruit of Xanthium strumarium to lower plasma

glucose in diabetic rats. Planta Med; 66(3): 228-30
Huang MT, Smart RC, Wong CQ, Conney AH (1988) Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-tetradecanoylphorbol-13-acetate. Cancer Res1; 48(21): 5941-6

Human JA, Ubbink JB, Jerling JJ, Delport R, Vermaak WJ, Vorster HH, Lagendijk J, Potgieter HC (1997) The effect of Simvastatin on the plasma antioxidant concentrations in patients with hypercholesterolaemia. Clin Chim Acta 4; 263(1): 67-77
Iwahashi H, Negoro Y, Ikeda A, Morishita H, Kido R (1986) Inhibition by chlorogenic acid of haematin-catalysed retinoic acid 5,6-epoxidation. Biochem J 1; 239(3): 641-6
Kasai H, Fukada S, Yamaizumi Z, Sugie S, Mori H (2000) Action of chlorogenic acid in vegetables and fruits as an inhibitor of 8-hydroxydeoxyguanosine formation in vitro and in a rat carcinogenesis model. Food Chem Toxicol 2000 1; 38 (5): 467-471

Kerry N, Rice-Ewans C (1999) Inhibition of peroxynitrite-mediated oxidation of Dopamine by flavonoid and phenolic antioxidants and their structural relationships. Journal of Neuroscience, 73, N1 pp. 247-253
Kim YK, Hwang MY, Woo JS, Jung JS, Lee SH (2000) Effect of arachidonic acid metabolic inhibitors on hypoxia/reoxygenationinduced renal cell injury. Ren Fail 2000; 22(2): 143-57
Kim SR, Kim YC (2000) Neuroprotective phenylpropanoid esters of rhamnose isolated from roots of Scrophularia buergeriana. Phytochemistry; 54(5): 503-9
King A, Young G (1999) Characteristics and occurrence of phenolic phytochemicals. J Am Diet Assoc; 99(2): 213-8

Kitts DD, Wijewickreme AN (1994) Effect of dietary caffeic and chlorogenic acids on in vivo xenobiotic enzyme systems. Plant Foods Hum Nutr. 45(3): 287-98
Kono Y, Shibata H, Kodama Y, Sawa Y (1995) The suppression of the N-nitrosating reaction by chlorogenic acid. Biochem J 15; 312, 947-953
Kono Y, Shibata H, Kodama Y, Ueda A, Sawa Y (1995) Chlorogenic acid as a natural scavenger for hypochlorous acid. Biochem Biophys Res Commun, 217(3): 972-8

Kono Y, Kobayashi K, Tagawa S, Adachi K, Ueda A, Sawa Y, Shibata H (1997) Antioxidant activity of polyphenolics in diets. Rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen. Biochim Biophys Acta, 1335 (3): 335-42
Kooy NW, Lewis SJ, Royall JA, Ye YZ, Kelly DR, Beckman JS (1997) Extensive tyrosine nitration in human myocardial inflammation: evidence for the presence of peroxynitrite. Crit Care Med 25(5):812-9
Koshihara Y, Neichi T, Murota S, Lao A, Fujimoto Y, Tatsuno T (1984) Caffeic acid is a selective inhibitor for leukotriene biosynthesis Biochim Biophys Acta 17; 792(1): 92-7
Millet J, et al. (1984) Improvement of blood filtrability with a purified extract of black currant anthocyanosides in cynomologus monkeys on a fat diet. J Pharmacol, 15: 439-45
Morton LW, Croft KD, Puddey IB, Byrne L (2000) Phenolic acids protect low-density lipoproteins from peroxynitrite-mediated modification in vitro. Redox Rep; 5(2-3): 124-5
Laranjinha J, Vieira O, Madeira V, Almeida L (1995) Two related phenolic antioxidants with opposite effects on vitamin E content in low density lipoproteins oxidized by ferrylmyoglobin: consumption vs regeneration. Arch Biochem Biophys, 323(2): 373-81

Laranjinha JA, Almeida LM, Madeira VM (1994) Reactivity of dietary phenolic acids with peroxyl radicals: antioxidant activity upon low-density lipoprotein peroxidation. Biochem Pharmacol, 48 (3): 487-94
Lo HH, Chung JG (1999) The effects of plant phenolics, caffeic acid, chlorogenic acid and ferulic acid on arylamine Nacetyltransferase activities in human gastrointestinal microflora. Anticancer Res; 19(1A): 133-9
Mortensen SA, Leth A, Agner E, Rohde M (1997) Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med; 18 Suppl: S137-44
Mori H, Tanaka T, Shima H, Kuniyasu T, Takahashi M (1986) Inhibitory effect of chlorogenic acid on methylazoxymethanol acetateinduced carcinogenesis in large intestine and liver of hamsters. Cancer Lett; 30 (1): 49-54

Nardini M, D'Aquino M, Tomassi G, Gentili V, Di Felice M, Scaccini C (1995) Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives. Free Radic Biol Med, 19(5): 541-52
Nardini M, Natella F, Gentili V, Di Felice M, Scaccini C (1997) Effect of caffeic acid dietary supplementation on the antioxidant defense system in rat: an in vivo study. Arch Biochem Biophys 1; 342(1): 157-160
NAS (1981) The health effects of nitrate, nitrite and N-nitroso compounds. Natl. Acad. of Sciences, Natl. Acad. Press Washington, D.C.

NAS. (1982) Diet, nutrition and cancer. Natl. Acad. of Sciences, Natl. Acad. Press, Washington, D.C.
Nicklaus M, Neamati N, Hong H, Mazumder A, Sunder S, Chen J, Milne G, Pommier Y (1997) HIV-1 integrase pharmacophore: discovery of inhibitors through three-dimensional database searching. J Med Chem, 40(6): 920-9
Paganga G, Miller N, Rice-Evans CA (1999) The polyphenolic content of fruit and vegetables and their antioxidant activities. What does a serving constitute? Free Radic Res; 30(2): 153-62
Robinson WE, Cordeiro M, Abdel-Malek S, Jia Q, Chow S, Reinecke M, Mitchell WM (1996) Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: inhibition of the core catalytic domain of human immunodeficiency virus integrase. Mol Pharmacol, 50(4): 846-55
Shimizu M, Yoshimi N, Yamada Y, Matsunaga K, Kawabata K, Hara A, Moriwaki H, Mori H (1999) Suppressive effects of chlorogenic acid on N-methyl-N-nitrosourea-induced glandular stomach carcinogenesis in male F344 rats. J Toxicol Sci; 24(5): 433-9
Sigal E, Laughton CW, Mulkins MA (1994) Oxidation, lipoxygenase, and atherogenesis. Ann N Y Acad Sci Apr 18; 714: 211-24

Tanaka T, Nishikawa A, Shima H, Sugie S (1990) Inhibitory effects of chlorogenic acid, reserpine, polyprenoic acid (E-5166), or coffee on hepatocarcinogenesis in rats and hamsters. Japan. Basic Life Sci; 52: 429-34
Thieme H, Winkler HJ (1966) On the occurrence of salidroside in the leaves of the red whortleberry (Vaccinium vitis-idaea L.). Pharmazie 21(3): 182
Thieme H, Walewska E, Winkler HJ (1969) Isolation of salidroside from leaves of Rhododendron. Pharmazie 24 (12): 783

Tsuchiya T, Suzuki 0, Igarashi K (1996) Protective effects of chlorogenic acid on paraquat-induced oxidative stress in rats. Bioscience Biotechnol Biochem; 60 (5): 765-8
Uz T, Pesold C, Longone P, Manev H (1998) Aging-associated up-regulation of neuronal 5-lipoxygenase expression: putative role in neuronal vulnerability. Journal ASEB; 12(6): 439-449
Vieira O, et al. (1998) Effect of dietary phenolic compounds on apoptosis of human cultured endothelial cells induced by oxidized LDL. J Pharmacology; 123 (3): 565-573
Yamada J, Tomita Y (1996) Antimutagenic activity of caffeic acid and related compounds. Biosci Biotechnol Biochem, 60(2): 328-9

 The Food and Drug Administration has not evaluated these statements. This product is not intended to diagnose, treat, cure or prevent any disease.
Copyright 2006 eFoodSafety.com