Supplements To Lower Blood Sugar: Part V (Conclusion)

*** Supplements and Herbs That Are Not Recommended***

Berberine: Berberine’s potent hypoglycemic effects have been demonstrated in multiple human studies with an ability to regulate glucose metabolism to an effect comparable or even identical to metformin (119-121) The concern is not whether or not berberine can lower blood sugar, as it does so remarkably, but how it may affect individuals long-term.

Berberine is a DPP-4 (dipeptidyl peptidase 4) inhibitor, and this is one way berberine can powerfully lower glucose (122). In clinical trials which are usually short-term (< 1 year), berberine’s short-term safety profile is overall favorable with side effects that are rare and mild (nasopharyngitis, headache, urinary tract infections inhibiting, and gastrointestinal symptoms that resolved with lowering the dosage). (123) Long-term use (>1 year), however, is what can cause serious adverse effects. Other than lowering blood sugar, DPP-4 also prevents the degradation of GLP-1 (glucagon-like peptide-1), which translates to enhanced action of incretin hormones. (124) Chronically elevated levels of GLP-1 from DPP-4 inhibitors do incite the proliferation of beta cells, which would normally be welcomed as it would increase the capacity for insulin production, but the sixfold increase in beta cell mass observed in a new study as a result of incretin therapy did not improve the diabetic condition since this growth was abnormal, with the potential to form a tumor. (125) These unique changes were only seen in those using such therapy for over a year, not in other diabetics who were not using this type of treatment. Other recent studies have noted significantly increased odds of acute pancreatitis and hospitalization in users of GLP-1-based therapies. (126-127)

Cinnamon:  Cinnamon activates genes that influence insulin signaling (112), and large amounts (1-6g) have lowered fasting glucose and decreased sugar spikes after meals (113-114), but these results are not always consistent (115), and more importantly, cinnamon also contains coumarin, which invites hepatotoxicity at therapeutic doses in animals. Heavy consumers of cinnamon from diet alone approach the tolerable daily intake. (116) It is likely that cinnamon taken daily at therapeutic doses will lead to toxic symptoms. Even ignoring its potential for toxicity, 1 gram only reduced insulin resistance in diabetics by <.1% in a well-controlled study. (117)

A variant of cinnamon without coumarin called Ceylon cinnamon or C. zeylanicum is bereft of the toxic threat of Cinamonmum cassia or C. cassia – the dominant form in the U.S. and the one used in studies – and unfortunately it also seems lack the same insulin-sensitizing ability. (118) Despite the fact that it does not appear to directly enhance the functioning of insulin, it can indirectly control blood glucose if used in the diet where sugar or fat would normally be substituted.

Galega Officinalis (Goat’s Rue, French Lilac): This guanidine-containing herb is considered a natural diabetes cure due to its active ingredient – guanidine, which metformin is derived from. It may be assumed that  this herb can serve as a metformin-like substitute to lower glucose levels, but unfortunately guanidine was considered too toxic for clinical use (128), hence the creation of metformin as a second-generation, safer alternative. Serious side effects such as hypotension, ataxia, seizures, and kidney and liver damage can result from using guanidine compounds. (129-132) There are also case reports of lactic acidosis with guanidine-derivatives.(133-134) While lactic acidosis is a risk also associated with metformin, the risk with metformin is much more rare since it is safer as a less lipophilic guanidine derivative. (147) Despite the fact that these ‘remedies’ are still sold and advertized as safe, natural alternatives for diabetes, use is not advised.

Total References:

1. Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med. 1999 Aug;27(3-4):309-14. (http://www.ncbi.nlm.nih.gov/pubmed/10468203)

2. Porasuphatana S, Suddee S, Nartnampong A, et al. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled study.Asia Pac J Clin Nutr. 2012;21(1):12-21. (http://www.ncbi.nlm.nih.gov/pubmed/22374556)

3. Cappelli V, Di Sabatino A, Musacchio MC, et al. Evaluation of a new association between insulin-sensitizers and α-lipoic acid in obese women affected by PCOS. Minerva Ginecol. 2013 Aug;65(4):425-33. (http://www.ncbi.nlm.nih.gov/pubmed/24051942)

4. McNeilly AM, Davison GW, Murphy MH, et al. Effect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance. Lipids Health Dis. 2011 Nov 22;10:217. doi: 10.1186/1476-511X-10-217. (http://www.ncbi.nlm.nih.gov/pubmed/22107734)

5. Klip A. Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway. Diabetes.1996;45(12):1798–1804. doi: 10.2337/diabetes.45.12.1798 (http://www.ncbi.nlm.nih.gov/pubmed/8922368)

6. Carneiro EM, Latorraca MQ, Araujo E, et al. Taurine supplementation modulates glucose homeostasis and islet function.J Nutr Biochem. 2009 Jul;20(7):503-11. doi: 10.1016/j.jnutbio.2008.05.008. Epub 2008 Aug 15. (http://www.ncbi.nlm.nih.gov/pubmed/18708284)

7. Lee E, Ryu GR, Ko SH, et al. Antioxidant treatment may protect pancreatic beta cells through the attenuation of islet fibrosis in an animal model of type 2 diabetes. Biochem Biophys Res Commun. 2011 Oct 22;414(2):397-402. doi: 10.1016/j.bbrc.2011.09.087. Epub 2011 Sep 24. (http://www.ncbi.nlm.nih.gov/pubmed/21971557)

8. El Mesallamy HO, El-Demerdash E, Hammad LN, et al. Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance. Diabetol Metab Syndr. 2010 Jun 30;2:46. doi: 10.1186/1758-5996-2-46. (http://www.ncbi.nlm.nih.gov/pubmed/20591133)

9. Elizarova EP, Nedosugova LV. First experiments in taurine administration for diabetes mellitus. Adv Exp Med Biol. 1996;403:583-8. (http://www.ncbi.nlm.nih.gov/pubmed/8915397)

10. P Kanetkar, R Singhal, and M Kamat. Gymnema sylvestre: A Memoir. J Clin Biochem Nutr. 2007 September; 41(2): 77–81. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170951/)

11. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, et al. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol. 1990 Oct;30(3):295-300. (http://www.ncbi.nlm.nih.gov/pubmed/2259217)

12. Alan Brian Cash. (2009). Patent No. WO2009114600 A2 (http://www.google.com/patents/WO2009114600A2?cl=en)

13. Yoshikawa K. Studies on Anti-diabetic Effect of Sodium Oxalcacetate. The Tohoku Journal of Experimental Medicine Vol. 96 (1968) No. 2 P 127-141 (http://www.ncbi.nlm.nih.gov/pubmed/4884771)

14. Cash A. Oxaloacetic Acid Supplementation as a Mimic of Calorie Restriction. Open Longevity Science, 2009, 3, 22-27 (http://www.benthamscience.com/open/tolsj/articles/V003/SI0016TOLSJ/22TOLSJ.pdf)

15. Gualano B, Novaes RB, Artioli GG, et al. Effects of creatine supplementation on glucose tolerance and insulin sensitivity in sedentary healthy males undergoing aerobic training. Amino Acids. 2008 Feb;34(2):245-50. Epub 2007 Mar 30. (http://www.ncbi.nlm.nih.gov/pubmed/17396216)

16. Cancela P, Ohanian C, Cuitiño E, et al. Creatine supplementation does not affect clinical health markers in football players. Br J Sports Med. 2008 Sep;42(9):731-5. doi: 10.1136/bjsm.2007.030700. (http://www.ncbi.nlm.nih.gov/pubmed/18780799)

17. Alves CR, Ferreira JC, de Siqueira-Filho MA, et al. Creatine-induced glucose uptake in type 2 diabetes: a role for AMPK-α? Amino Acids. 2012 Oct;43(4):1803-7. Epub 2012 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/22349765)

18. Kanter M, Meral I, Yener Z, et al. Partial regeneration/proliferation of the beta-cells in the islets of Langerhans by Nigella sativa L. in streptozotocin-induced diabetic rats. Tohoku J Exp Med. 2003 Dec;201(4):213-9. (http://www.ncbi.nlm.nih.gov/pubmed/14690013)

19. Alimohammadi S, Hobbenaghi R, Javanbakht J,et al. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagn Pathol. 2013 Aug 15;8:137. doi: 10.1186/1746-1596-8-137. (http://www.ncbi.nlm.nih.gov/pubmed/23947821)

20. Talaei A, Mohamadi M, Adgi Z. The effect of vitamin D on insulin resistance in patients with type 2 diabetes. Diabetol Metab Syndr. 2013 Feb 26;5(1):8. doi: 10.1186/1758-5996-5-8. (http://www.ncbi.nlm.nih.gov/pubmed/23443033)

21. Chiu KC, Chu A, Go VL, et al. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004 May;79(5):820-5. (http://www.ncbi.nlm.nih.gov/pubmed/15113720)

22. Joanna Mitri, Bess Dawson-Hughes, Frank B Hu, et al. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trialAm J Clin Nutr August 2011 vol. 94 no. 2 486-494 (http://www.ncbi.nlm.nih.gov/pubmed/21715514)

23. Maestro B, Dávila N, Carranza MC, et al. Identification of a Vitamin D response element in the human insulin receptor gene promoter. J Steroid Biochem Mol Biol. 2003 Feb;84(2-3):223-30. (http://www.ncbi.nlm.nih.gov/pubmed/12711007)

24. Tamilselvan B, Seshadri KG, Venkatraman G. Role of vitamin D on the expression of glucose transporters in L6 myotubes. Indian J Endocr Metab 2013;17:326-8 (http://www.ijem.in/article.asp?issn=2230-8210;year=2013;volume=17;issue=7;spage=326;epage=328;aulast=Tamilselvan)

25. Li YC. Vitamin D regulation of the renin-angiotensin system. J Cell Biochem. 2003 Feb 1;88(2):327-31. (http://www.ncbi.nlm.nih.gov/pubmed/12520534)

26. Luther JM, Brown NJ. The renin-angiotensin-aldosterone system and glucose homeostasis. Trends Pharmacol Sci. 2011 Dec;32(12):734-9. doi: 10.1016/j.tips.2011.07.006. Epub 2011 Aug 29. (http://www.ncbi.nlm.nih.gov/pubmed/21880378)

27. Takaya J, Higashino H, Kobayashi Y. Intracellular magnesium and insulin resistance. Magnes Res. 2004 Jun;17(2):126-36. (http://www.ncbi.nlm.nih.gov/pubmed/15319146)

28. Rosanoff A, Weaver CM, Rude RK. Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutr Rev. 2012 Mar;70(3):153-64. doi: 10.1111/j.1753-4887.2011.00465.x. Epub 2012 Feb 15. (http://www.ncbi.nlm.nih.gov/pubmed/22364157)

29. Guerrero-Romero F, Rodríguez-Morán M. Magnesium improves the beta-cell function to compensate variation of insulin sensitivity: double-blind, randomized clinical trial. Eur J Clin Invest. 2011 Apr;41(4):405-10. doi: 10.1111/j.1365-2362.2010.02422.x. Epub 2011 Jan 17. (http://www.ncbi.nlm.nih.gov/pubmed/21241290)

30. Rodríguez-Morán M, Guerrero-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care. 2003 Apr;26(4):1147-52. (http://www.ncbi.nlm.nih.gov/pubmed/12663588)

31. Mooren FC, Krüger K, Völker K, et al. Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects – a double-blind, placebo-controlled, randomized trial. Diabetes Obes Metab. 2011 Mar;13(3):281-4. doi: 10.1111/j.1463-1326.2010.01332.x. (http://www.ncbi.nlm.nih.gov/pubmed/21205110)

32. Yokota K, Kato M, Lister F,et al. Clinical efficacy of magnesium supplementation in patients with type 2 diabetes. J Am Coll Nutr. 2004 Oct;23(5):506S-509S. (http://www.ncbi.nlm.nih.gov/pubmed/15466952)

33. Wang H, Kruszewski A, Brautigan DL. Cellular chromium enhances activation of insulin receptor kinase. Biochemistry. 2005 Jun 7;44(22):8167-75. (http://www.ncbi.nlm.nih.gov/pubmed/15924436)

34. Schwarz K, Mertz W. Chromium (III) and the glucose tolerance factor. Arch Biochem Biophys 85: 292–295, 1959 (http://www.ncbi.nlm.nih.gov/pubmed/14444068)

35. Jovanovic L, Gutierrez M, Peterson CM. Chromium supplementation for women with gestational diabetes mellitus. J Trace Elem Exp Med 12:91–97,1999 (http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1520-670X(1999)12:2%3C91::AID-JTRA6%3E3.0.CO;2-X/abstract)

36. Cheng N, Zhu X, Shi H, et al. Follow-up survey of people in China with type 2 diabetes mellitus consuming supplemental chromium. J Trace Elem Exp Med 12:55–60, 1999 (http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1520-670X(1999)12:2%3C55::AID-JTRA2%3E3.0.CO;2-G/abstract)

37. Uusitupa MI, Kumpulainen JT, Voutilainen E, et al. Effect of inorganic chromium supplementation on glucose tolerance, insulin response, and serum lipids in noninsulin-dependent diabetics. Am J Clin Nutr 38:404–410, 1983 (http://www.ncbi.nlm.nih.gov/pubmed/6351586)

38. Ravina A, Slezak L, Rubal A, et al. Clinical use of the trace element chromium (III) in the treatment of diabetes mellitus. J Trace Elem Exp Med 8:183–190, 1995

39. Ravina A, Slezak L, Mirsky N, et al. Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabet Med 16:164–167, 1999 (http://www.ncbi.nlm.nih.gov/pubmed/10229312)

40. Masharani U, Gjerde C, McCoy S, et al. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocr Disord. 2012 Nov 30;12:31. doi: 10.1186/1472-6823-12-31. (http://www.ncbi.nlm.nih.gov/pubmed/23194380)

41. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14 (http://www.ncbi.nlm.nih.gov/pubmed/15208835)

42. Abraham AS, Brooks BA, Eylath U. The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes. Metabolism 41:768–771, 1992 (http://www.ncbi.nlm.nih.gov/pubmed/1619996)

43. Lee NA, Reasner CA. Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM. Diabetes Care 17:1449–1452, 1994 (http://www.ncbi.nlm.nih.gov/pubmed/7882815)

44. Uusitupa MI, Kumpulainen JT, Voutilainen E, et al. Effect of inorganic chromium supplementation on glucose tolerance, insulin response, and serum lipids in noninsulin-dependent diabetics. Am J Clin Nutr 38:404–410, 1983 (http://www.ncbi.nlm.nih.gov/pubmed/6351586)

45. Golubnitschaja O, Yeghiazaryan K. Opinion controversy to chromium picolinate therapy’s safety and efficacy: ignoring ‘anecdotes’ of case reports or recognising individual risks and new guidelines urgency to introduce innovation by predictive diagnostics? EPMA J. 2012; 3(1): 11 (http://www.ncbi.nlm.nih.gov/pubmed/23039227)

46. Olatunji LA, Soladoye AO. Low dietary folate impairs glucose tolerance and plasma lipid profile in oral contraceptive-treated rats. Pathophysiology. 2008 Oct;15(3):167-71. doi: 10.1016/j.pathophys.2008.04.001. Epub 2008 Jun 24. (http://www.ncbi.nlm.nih.gov/pubmed/18572393)

47. Buettner R, Bettermann I, Hechtl C, et al. Dietary folic acid activates AMPK and improves insulin resistance and hepatic inflammation in dietary rodent models of the metabolic syndrome. Horm Metab Res. 2010 Oct;42(11):769-74. doi: 10.1055/s-0030-1263122. Epub 2010 Aug 27. (http://www.ncbi.nlm.nih.gov/pubmed/20803414)

48. Greenberg JA, Bell SJ. Multivitamin Supplementation During Pregnancy: Emphasis on Folic Acid and l-Methylfolate. Rev Obstet Gynecol. 2011; 4(3-4): 126–127. (http://www.ncbi.nlm.nih.gov/pubmed/22229066)
49. Luong KV, Nguyen LT .The impact of thiamine treatment in the diabetes mellitus. J Clin Med Res. 2012 June; 4(3): 153–160. (http://www.ncbi.nlm.nih.gov/pubmed/22719800)

50. Thornalley PJ. The potential role of thiamine (vitamin B1) in diabetic complications. Curr Diabetes Rev. 2005 Aug;1(3):287-98. (http://www.ncbi.nlm.nih.gov/pubmed/18220605)

51. Alaei Shahmiri F, Soares MJ, Zhao Y, et al. High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial. Eur J Nutr. 2013 Oct;52(7):1821-4. doi: 10.1007/s00394-013-0534-6. Epub 2013 May 29. (http://link.springer.com/article/10.1007%2Fs00394-013-0534-6)

52. Rao KS, Mohan PS. Plasma somatomedin activity, growth-hormone and insulin levels in vitamin B6 deficient rats. Horm Metab Res. 1982 Nov;14(11):580-2. (http://www.ncbi.nlm.nih.gov/pubmed/6759353)

53. Rao RH. Glucose tolerance in subclinical pyridoxine deficiency in man. Am J Clin Nutr. 1983 Sep;38(3):440-4. (http://www.ncbi.nlm.nih.gov/pubmed/6351588)

54. Rose DP, Leklem JE, Brown RR, et al. Effect of oral contraceptives and vitamin B6 deficiency on carbohydrate metabolism. Am J Clin Nutr. 1975 Aug;28(8):872-8. (http://www.ncbi.nlm.nih.gov/pubmed/1146747)

55. Kiran SG, Dorisetty RK, Umrani MR, et al. Pyridoxal 5′ phosphate protects islets against streptozotocin-induced beta-cell dysfunction–in vitro and in vivo. Exp Biol Med (Maywood). 2011 Apr 1;236(4):456-65. doi: 10.1258/ebm.2011.010361. Epub 2011 Apr 4. (http://www.ncbi.nlm.nih.gov/pubmed/21464101)

56. Takatori A, Ishii Y, Itagaki S, et al. Amelioration of the beta-cell dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor treatments. Diabetes Metab Res Rev. 2004 May-Jun;20(3):211-8. (http://www.ncbi.nlm.nih.gov/pubmed/15133752)

57. Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. 2007 Nov;126(5):471-4. (http://www.ncbi.nlm.nih.gov/pubmed/18160753)

58. Paolisso G, D’Amore A, Balbi V, et al. Plasma vitamin C affects glucose homeostasis in healthy subjects and in non-insulin-dependent diabetics. Am J Physiol. 1994 Feb;266(2 Pt 1):E261-8. (http://www.ncbi.nlm.nih.gov/pubmed/8141285)

59. Tsujinaka K, Nakamura T, Maegawa H, et al. Diet high in lipid hydroperoxide by vitamin E deficiency induces insulin resistance and impaired insulin secretion in normal rats. Diabetes Res Clin Pract. 2005 Feb;67(2):99-109. (http://www.ncbi.nlm.nih.gov/pubmed/15649568)

60. Paolisso G, D’Amore A, Galzerano D, et al. Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients. Diabetes Care. 1993 Nov;16(11):1433-7. (http://www.ncbi.nlm.nih.gov/pubmed/8299431)

61. Fang F, Kang Z, Wong C. Vitamin E tocotrienols improve insulin sensitivity through activating peroxisome proliferator-activated receptors. Mol Nutr Food Res. 2010 Mar;54(3):345-52. doi: 10.1002/mnfr.200900119. (http://www.ncbi.nlm.nih.gov/pubmed/19866471)

62. Serbinova E, Kagan V, Han D, et al. Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol. Free Radic Biol Med. 1991;10(5):263-75. (http://www.ncbi.nlm.nih.gov/pubmed/1649783)

63. Facchini FS, Humphreys MH, DoNascimento CA, et al. Relation between insulin resistance and plasma concentrations of lipid hydroperoxides, carotenoids, and tocopherols. Am J Clin Nutr. 2000 Sep;72(3):776-9. (http://www.ncbi.nlm.nih.gov/pubmed/10966898)

64. Bhuvaneswari S, Anuradha CV. Astaxanthin prevents loss of insulin signaling and improves glucose metabolism in liver of insulin resistant mice. Can J Physiol Pharmacol. 2012 Nov;90(11):1544-52. doi: 10.1139/y2012-119. Epub 2012 Nov 13. (http://www.ncbi.nlm.nih.gov/pubmed/23181282)

65. Uchiyama K, Naito Y, Hasegawa G, et al. Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice. Redox Rep. 2002;7(5):290-3. (http://www.ncbi.nlm.nih.gov/pubmed/12688512)

66. Soltani N, Qiu H, Aleksic M, et al. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11692-7. doi: 10.1073/pnas.1102715108. Epub 2011 Jun 27. (http://www.pnas.org/content/early/2011/06/22/1102715108)

67. Cavagnini F, Pinto M, Dubini A, et al. Effects of gamma aminobutyric acid (GABA) and muscimol on endocrine pancreatic function in man. Metabolism. 1982 Jan;31(1):73-7. (http://www.ncbi.nlm.nih.gov/pubmed/7043162)

68. Tang X, Shay NF. Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes. J Nutr. 2001 May;131(5):1414-20. (http://www.ncbi.nlm.nih.gov/pubmed/11340092)

69. Jansen J, Karges W, Rink L. Zinc and diabetes–clinical links and molecular mechanisms. J Nutr Biochem. 2009 Jun;20(6):399-417. doi: 10.1016/j.jnutbio.2009.01.009. (http://www.ncbi.nlm.nih.gov/pubmed/19442898)

70. Ortega RM, Rodríguez-Rodríguez E, Aparicio A, et al. Poor zinc status is associated with increased risk of insulin resistance in Spanish children. Br J Nutr. 2012 Feb;107(3):398-404. doi: 10.1017/S0007114511003114. (http://www.ncbi.nlm.nih.gov/pubmed/22277170)

71. Raz I, Karsai D, Katz M. The influence of zinc supplementation on glucose homeostasis in NIDDM. Diabetes Res. 1989 Jun;11(2):73-9. (http://www.ncbi.nlm.nih.gov/pubmed/2695282)

72. Gunasekara, P et al. Effects of zinc and multimineral vitamin supplementation on glycemic and lipid control in adult diabetes. Diabetes Metab Syndr Obes. 2011 Jan 26;4:53-60. (http://www.ncbi.nlm.nih.gov/pubmed/21448322)

73. Al-Maroof RA, Al-Sharbatti SS. Serum zinc levels in diabetic patients and effect of zinc supplementation on glycemic control of type 2 diabetics. Saudi Med J. 2006 Mar;27(3):344-50. (http://www.ncbi.nlm.nih.gov/pubmed/16532095)

74. Afkhami-Ardekani M, Karimi M, Mohammadi SM, Nourani F. Effect of zinc sulfate supplementation on lipid and glucose in type 2 diabetic patients. Pak J Nutr.2008;7:550–553. doi: 10.3923/pjn.2008.550.553. (http://www.pjbs.org/pjnonline/fin941.pdf)

75. Hughes S, Samman S. The effect of zinc supplementation in humans on plasma lipids, antioxidant status and thrombogenesis. J Am Coll Nutr. 2006 Aug;25(4):285-91. (http://www.ncbi.nlm.nih.gov/pubmed/16943449)

76. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res. 2006 Dec;20(12):1036-9. (http://www.ncbi.nlm.nih.gov/pubmed/17072885)

77. Velussi M, Cernigoi AM, De Monte A, et al. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol. 1997 Apr;26(4):871-9. (http://www.ncbi.nlm.nih.gov/pubmed/9126802)

78. Agrawal P, Rai V, Singh RB. Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus. Int J Clin Pharmacol Ther. 1996 Sep;34(9):406-9. (http://www.ncbi.nlm.nih.gov/pubmed/8880292)

79. Rai V, Mani UV, Iyer UM. Effect of Ocimum sanctum Leaf Powder on Blood Lipoproteins, Glycated Proteins and Total Amino Acids in Patients with Non-insulin-dependent Diabetes Mellitus. Journal of Nutritional & Environmental Medicine (1997) 7, 113-118. (http://informahealthcare.com/doi/abs/10.1080/13590849762709)

80. Hannan JM, Marenah L, Ali L, et al. Ocimum sanctum leaf extracts stimulate insulin secretion from perfusd pancreas, isolated islets and clonal pancreatic beta-cells. J Endocrinol. 2006;189:127–36. (http://www.ncbi.nlm.nih.gov/pubmed/16614387)

81. Gholap S, Kar A. Hypoglycemic effects of some plant extracts are possibly mediated through inhibition in corticosteroid concentration. Pharmazie. 2004;59:876–8. (http://www.ncbi.nlm.nih.gov/pubmed/15587591)

82. Beulens JW, van der A DL, Grobbee DE, et al. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care. 2010 Aug;33(8):1699-705. doi: 10.2337/dc09-2302. Epub 2010 Apr 27. (http://www.ncbi.nlm.nih.gov/pubmed/20424220)

83. Choi HJ, Yu J, Choi H, et al. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care. 2011 Sep;34(9):e147. doi: 10.2337/dc11-0551. (http://www.ncbi.nlm.nih.gov/pubmed/21868771)

84. Shea MK, Gundberg CM, Meigs JB, et al. Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr. 2009 Nov;90(5):1230-5. doi: 10.3945/ajcn.2009.28151. Epub 2009 Sep 23. (http://www.ncbi.nlm.nih.gov/pubmed/19776145)

85. Shea MK, Booth SL, Massaro JM, et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol. 2008 Feb 1;167(3):313-20. Epub 2007 Nov 15. (http://www.ncbi.nlm.nih.gov/pubmed/18006902)

86. van Dam RM, Feskens EJ. Coffee consumption and risk of type 2 diabetes mellitus. Lancet. 2002 Nov 9;360(9344):1477-8. (http://www.ncbi.nlm.nih.gov/pubmed/12433517)

87. 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. (http://www.ncbi.nlm.nih.gov/pubmed/16801515)

88. Lee S, Hudson R, Kilpatrick K, et al. Caffeine ingestion is associated with reductions in glucose uptake independent of obesity and type 2 diabetes before and after exercise training. Diabetes Care. 2005 Mar;28(3):566-72. ( http://www.ncbi.nlm.nih.gov/pubmed/15735189)

89. Ho L, Varghese M, Wang J, et al. Dietary supplementation with decaffeinated green coffee improves diet-induced insulin resistance and brain energy metabolism in mice. Nutr Neurosci. 2012 Jan;15(1):37-45. doi: 10.1179/1476830511Y.0000000027. (http://www.ncbi.nlm.nih.gov/pubmed/22305652)

90. Shengxi Meng, Jianmei Cao, Qin Feng, et al. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review. Evid Based Complement Alternat Med. 2013; 2013: 801457. (http://www.ncbi.nlm.nih.gov/pubmed/24062792)

91. Blum J, Lemaire B, Lafay S. Effect of a green decaffeinated coffee extract on glycaemia. NutraFoods Res. 2007;6:13–7. (http://www.nuvocare.us/assets/pdf/SVETOL_Blood%20Sugar%20Study.pdf)

92. Movahed A, Nabipour I, Lieben Louis X, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med. 2013;2013:851267. doi: 10.1155/2013/851267. Epub 2013 Sep 1. (http://www.ncbi.nlm.nih.gov/pubmed/24073011)

93. Brasnyó P, Molnár GA, Mohás M, et al. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. British Journal of Nutrition. 2011;106(3):383–389. (http://www.ncbi.nlm.nih.gov/pubmed/21385509)

94. Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutrition Research. 2012;32:537–541. (http://www.ncbi.nlm.nih.gov/pubmed/22901562)

95. Crandall JP, Oram V, Trandafirescu G, et al. Pilot study of resveratrol in older adults with impaired glucose tolerance. The Journals of Gerontology A. 2012;67:1307–1312. *(http://www.ncbi.nlm.nih.gov/pubmed/22219517)

96. AP Simopoulos. Dietary Omega-3 Fatty Acid Deficiency and High Fructose intake in the Development of Metabolic Syndrome Brain, Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease. Nutrients. 2013 August; 5(8): 2901–2923. (http://www.ncbi.nlm.nih.gov/pubmed/23896654)

97. Zhu QQ, Lou DJ, Si XW, et al. Serum omega-3 polyunsaturated fatty acid and insulin resistance in type 2 diabetes mellitus and non-alcoholic fatty liver disease. Zhonghua Nei Ke Za Zhi. 2010 Apr;49(4):305-8. (http://www.ncbi.nlm.nih.gov/pubmed/20627036)

98. Virtanen JK, Mursu J, Voutilainen S, et al. Serum omega-3 polyunsaturated Fatty acids and risk of incident type 2 diabetes in men: the kuopio ischemic heart disease risk factor study. Diabetes Care. 2014 Jan;37(1):189-96. doi: 10.2337/dc13-1504. Epub 2013 Sep 11. (http://www.ncbi.nlm.nih.gov/pubmed/24026545)

99. Tsitouras PD, Gucciardo F, Salbe AD, et al. High omega-3 fat intake improves insulin sensitivity and reduces CRP and IL6, but does not affect other endocrine axes in healthy older adults. Horm Metab Res. 2008 Mar;40(3):199-205. doi: 10.1055/s-2008-1046759. (http://www.ncbi.nlm.nih.gov/pubmed/18348080)

100. Rafraf M, Mohammadi E, Asghari-Jafarabadi M, et al. Omega-3 fatty acids improve glucose metabolism without effects on obesity values and serum visfatin levels in women with polycystic ovary syndrome. J Am Coll Nutr. 2012 Oct;31(5):361-8. (http://www.ncbi.nlm.nih.gov/pubmed/23529993)

101. Udupa A, Nahar P, Shah S, et al. A Comparative Study of Effects of Omega-3 Fatty Acids, Alpha Lipoic Acid and Vitamin E in Type 2 Diabetes Mellitus. Ann Med Health Sci Res. 2013 Jul;3(3):442-6. doi: 10.4103/2141-9248.117954. (http://www.ncbi.nlm.nih.gov/pubmed/24116330)

102. Pooya S, Jalali MD, Jazayery AD, Saedisomeolia A, Eshraghian MR, Toorang F. The efficacy of omega-3 fatty acid supplementation on plasma homocysteine and malondialdehyde levels of type 2 diabetic patients. Nutr Metab Cardiovasc Dis. 2009 Jun 18. (http://www.ncbi.nlm.nih.gov/pubmed/19540739)

103. Hartweg J, Perera R, Montori VM, et al. Omega‐3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD003205. DOI: 10.1002/14651858.CD003205.pub2. (http://www.ncbi.nlm.nih.gov/pubmed/18254017)

104. Vessby B, Boberg M. Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. J Intern Med. 1990 Aug;228(2):165-71. (http://www.ncbi.nlm.nih.gov/pubmed/2394967)

105. Akinosun OM, Bolajoko EB. Total antioxidant status in type 2 diabetic patients: experience at University College Hospital (UCH) Ibadan, Nigeria. Niger J Clin Pract. 2007 Jun;10(2):126-9. (http://www.ncbi.nlm.nih.gov/pubmed/17902504)

106. Ogihara T, Asano T, Katagiri H, et al. Oxidative stress induces insulin resistance by activating the nuclear factor-kappa B pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase. Diabetologia. 2004 May;47(5):794-805. Epub 2004 May 1. (http://www.ncbi.nlm.nih.gov/pubmed/15127200)

107. Véricel E, Polette A, Bacot S, et al. Pro- and antioxidant activities of docosahexaenoic acid on human blood platelets. J Thromb Haemost. 2003 Mar;1(3):566-72. (http://www.ncbi.nlm.nih.gov/pubmed/12871467)

108. Luostarinen R, Wallin R, Wibell R, Saldeen T. Vitamin E supplementation counteracts the fish oil-induced increase in blood glucose in humans. Nutr Res. 1995;15:953–68. (http://www.sciencedirect.com/science/article/pii/027153179500057P)

109. Muldoon MF, Erickson KI, Goodpaster BH, et al. Concurrent physical activity modifies the association between n3 long-chain fatty acids and cardiometabolic risk in midlife adults. J Nutr. 2013 Sep;143(9):1414-20. doi: 10.3945/jn.113.174078. Epub 2013 Jul 24. (http://www.ncbi.nlm.nih.gov/pubmed/23884386)

110. Vaughan RA, Garcia-Smith R, Bisoffi M, et al. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells. Lipids Health Dis. 2012 Oct 30;11:142. doi: 10.1186/1476-511X-11-142. (http://www.ncbi.nlm.nih.gov/pubmed/23107305)

111. Patterson E, Wall R, Fitzgerald GF, et al. Health implications of high dietary omega-6 polyunsaturated Fatty acids. J Nutr Metab. 2012;2012:539426. doi: 10.1155/2012/539426. Epub 2012 Apr 5. (http://www.ncbi.nlm.nih.gov/pubmed/22570770)

112. Sheng X, Zhang Y, Gong Z, et al. Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors. PPAR Res. 2008;2008:581348. doi: 10.1155/2008/581348. Epub 2008 Dec 11. (http://www.ncbi.nlm.nih.gov/pubmed/19096709)

113. Magistrelli A, Chezem JC. Effect of ground cinnamon on postprandial blood glucose concentration in normal-weight and obese adults. J Acad Nutr Diet. 2012 Nov;112(11):1806-9. doi: 10.1016/j.jand.2012.07.037. (http://www.ncbi.nlm.nih.gov/pubmed/23102179)

114. Khan A, Safdar M, Ali Khan MM, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003 Dec;26(12):3215-8. (http://www.ncbi.nlm.nih.gov/pubmed/14633804)

115. Vanschoonbeek K, Thomassen BJ, Senden JM, et al. Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients. J Nutr. 2006 Apr;136(4):977-80. (http://jn.nutrition.org/content/136/4/977.short)

116. Abraham K, Wöhrlin F, Lindtner O, et al. Toxicology and risk assessment of coumarin: focus on human data. Mol Nutr Food Res. 2010 Feb;54(2):228-39. doi: 10.1002/mnfr.200900281. (http://www.ncbi.nlm.nih.gov/pubmed/20024932)

117. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med. 2009 Sep-Oct;22(5):507-12. doi: 10.3122/jabfm.2009.05.080093. (http://www.ncbi.nlm.nih.gov/pubmed/19734396)

118. Wickenberg J, Lindstedt S, Berntorp K, et al. Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance. Br J Nutr. 2012 Jun;107(12):1845-9. doi: 10.1017/S0007114511005113. Epub 2011 Sep 20. (http://www.ncbi.nlm.nih.gov/pubmed/21929834)

119. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008 May;57(5):712-7. doi: 10.1016/j.metabol.2008.01.013. (http://www.ncbi.nlm.nih.gov/pubmed/18442638)

120. Zhang H, Wei J, Xue R, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. 2010 Feb;59(2):285-92. doi: 10.1016/j.metabol.2009.07.029. Epub 2009 Oct 1. (http://www.ncbi.nlm.nih.gov/pubmed/19800084)

121. Dong H, Wang N, Zhao L, et al. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. 2012;2012:591654. doi: 10.1155/2012/591654. Epub 2012 Oct 15. (http://www.ncbi.nlm.nih.gov/pubmed/23118793)

122. Al-masri IM, Mohammad MK, Tahaa MO. Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine. J Enzyme Inhib Med Chem. 2009 Oct;24(5):1061-6. doi: 10.1080/14756360802610761. (http://www.ncbi.nlm.nih.gov/pubmed/19640223)

123. Mikhail N. Safety of dipeptidyl peptidase 4 inhibitors for treatment of type 2 diabetes. Curr Drug Saf. 2011 Nov 1;6(5):304-9. (http://www.ncbi.nlm.nih.gov/pubmed/22424537)

124. Capuano A, Sportiello L, Maiorino MI, et al. Dipeptidyl peptidase-4 inhibitors in type 2 diabetes therapy–focus on alogliptin. Drug Des Devel Ther. 2013 Sep 17;7:989-1001. doi: 10.2147/DDDT.S37647. (http://www.ncbi.nlm.nih.gov/pubmed/24068868)

125. Butler AE, Campbell-Thompson M, Gurlo T, et al. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 2013 Jul;62(7):2595-604. doi: 10.2337/db12-1686. Epub 2013 Mar 22. (http://www.ncbi.nlm.nih.gov/pubmed/23524641)

126. Singh S, Chang HY, Richards TM, et al. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med. 2013 Apr 8;173(7):534-9. doi: 10.1001/jamainternmed.2013.2720. (http://www.ncbi.nlm.nih.gov/pubmed/23440284)

127. Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies.Gastroenterology. 2011 Jul;141(1):150-6. doi: 10.1053/j.gastro.2011.02.018. Epub 2011 Feb 18. (http://www.ncbi.nlm.nih.gov/pubmed/21334333)

128. Modak M, Dixit P, Londhe J, et al. Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr. 2007 May;40(3):163-73. doi: 10.3164/jcbn.40.163. (http://www.ncbi.nlm.nih.gov/pubmed/18398493)

129. Samuelsen GS. An investigation of the toxicity and hypoglycemic effect of several guanidine compounds. J Pharmacol Exp Ther 1935;51:17-24. (http://jpet.aspetjournals.org/content/54/1/17.short)

130. Blatherwick NR, Sahyun M, Hill E. Some effects of synthalin on metabolism. J Biol Chem 1927;75:671-82. (http://www.jbc.org/content/75/3/671.full.pdf)

131. Bodo R, Marks HP. The relation of synthalin to carbohydrate metabolism. J Physiol. 1928;65:83-99. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1515020/)

132. Mori A. Biochemistry and neurotoxicology of guanidino compounds. History and recent advances. Pavlov J Biol Sci. 1987 Jul-Sep;22(3):85-94. (http://www.ncbi.nlm.nih.gov/pubmed/2821470)

133. Kwong SC, Brubacher J. Phenformin and lactic acidosis: a case report and review. J Emerg Med 1998; 16:881-6 (http://www.ncbi.nlm.nih.gov/pubmed/9848705)

134. Butt H, Reitinger J. Lactic acidosis after administration of guanidine derivatives (buformine, phenformine). Med Klin. 1977 Apr 22;72(16):708-11. (http://www.ncbi.nlm.nih.gov/pubmed/857140)

135. S., Chuengsamarn, S., Rattanamongkolgul, S., Luechapudiporn, R., et al. S., 2012. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 3S (11). 2121-2127. (http://www.ncbi.nlm.nih.gov/pubmed/22773702)

136. Srinivasan M. Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci. 1972;26:269–270. (http://www.ncbi.nlm.nih.gov/pubmed/4637293)

137. Seo KI, Choi MS, Jung UJ, et al. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol Nutr Food Res. 2008 Sep;52(9):995-1004. doi: 10.1002/mnfr.200700184. (http://www.ncbi.nlm.nih.gov/pubmed/18398869)

138. Wickenberg J, Ingemansson SL, Hlebowicz J. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr J. 2010 Oct 12;9:43. doi: 10.1186/1475-2891-9-43. (http://www.ncbi.nlm.nih.gov/pubmed/20937162)

139. Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998 May;64(4):353-6. (http://www.ncbi.nlm.nih.gov/pubmed/9619120)

140. Schiborr C, Kocher A, Behnam D, et al. The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res. 2014 Jan 9. doi: 10.1002/mnfr.201300724. [Epub ahead of print] (http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201300724/abstract)

141: Munin A, Edwards-Lévy F. Encapsulation of natural polyphenolic compounds; a review. Pharmaceutics. 2011 Nov 4;3(4):793-829. doi: 10.3390/pharmaceutics3040793. (http://www.mdpi.com/1999-4923/3/4/793)

142. Marczylo TH, Verschoyle RD, Cooke DN, et al. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol. 2007 Jul;60(2):171-7. Epub 2006 Oct 19. (http://www.ncbi.nlm.nih.gov/pubmed/17051370)

143. Qatanani M, Lazar MA. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 2007 Jun 15;21(12):1443-55. (http://www.ncbi.nlm.nih.gov/pubmed/17575046)

144. Acharya SD, Brooks MM, Evans RW, et al. Weight loss is more important than the diet type in improving adiponectin levels among overweight/obese adults.J Am Coll Nutr. 2013;32(4):264-71. doi: 10.1080/07315724.2013.816607. (http://www.ncbi.nlm.nih.gov/pubmed/24024771)

145. Moon JK, Yoo HS, Shibamoto T. Role of roasting conditions in the level of chlorogenic acid content in coffee beans: correlation with coffee acidity. J Agric Food Chem. 2009 Jun 24;57(12):5365-9. doi: 10.1021/jf900012b. (http://www.ncbi.nlm.nih.gov/pubmed/19530715)

146. Maradana MR, Thomas R, O’Sullivan BJ. Targeted delivery of curcumin for treating type 2 diabetes. Mol Nutr Food Res. 2013 Sep;57(9):1550-6. doi: 10.1002/mnfr.201200791. Epub 2013 Mar 14. (http://www.ncbi.nlm.nih.gov/pubmed/23495213)

147. Witters LA. The blooming of the French lilac. J Clin Invest. 2001 Oct;108(8):1105-7. (http://www.ncbi.nlm.nih.gov/pubmed/11602616)

148. Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996;93(8):3704-3709. (http://www.pnas.org/content/93/8/3704)

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s