DIABETES

Alpha Lipoic Acid

1. Doses of controlled-release alpha-lipoic acid (900 mg/day for 6 weeks then 1200 mg/day for 6 weeks) effectively reduced plasma fructosamine and were well tolerated by patients with type 2 diabetes.

Endocr Pract. 2002 Jan-Feb;8(1):29-35.
Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid.
Evans JL, Heymann CJ, Goldfine ID, Gavin LA.

2. Daily doses of alpha-lipoic acid (600 mg for 18 months) decreased the thrombomodulin levels in patients with diabetes and a urinary albumin concentration of less than 200 mg/l compared to the control group. Antioxidant treatment may be beneficial in diabetes, as oxidative stress is believed to be an originating factor in the diabetic nephropathy.

Diabetes Res Clin Pract. 2001 Jun;52(3):175-83.
Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study.
Morcos M, Borcea V, Isermann B, Gehrke S, Ehret T, Henkels M, Schiekofer S, Hofmann M, Amiral J, Tritschler H, Ziegler R, Wahl P, Nawroth PP.

3. Two types of dosing of alpha-lipoic acid (1200 mg/day for 6 weeks or 600 mg intravenously over 15 minutes) were both effective in increasing microcirculation in diabetic patients with polyneuropathy.

Exp Clin Endocrinol Diabetes. 2000;108(3):168-74.
Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy.
Haak E, Usadel KH, Kusterer K, Amini P, Frommeyer R, Tritschler HJ, Haak T.
Medical Department I, Center of Internal Medicine, University Hospital,
Frankfurt, Germany. E.Haak@em.uni-frankfurt.de

4. Daily doses of alpha-lipoic acid (600 mg/day for 70 days) reduce lipid peroxidation and also correct, and potentially prevent, diabetic neuropathy.

In Vivo. 2000 Mar-Apr;14(2):327-30.
In vivo effect of lipoic acid on lipid peroxidation in patients with diabetic neuropathy.
Androne L, Gavan NA, Veresiu IA, Orasan R.
Diabetes Center & Clinic, Cluj Napoca.

5. A number of measures were used to examine the extent to which oral doses of alpha-lipoic acid (600 mg/3 times/day for 3 weeks) improved symptoms of polyneuropathy in patients with Type 2 diabetes. Compared to placebo, the supplement group had decreased scores in Total Symptom Score (describing foot pain, burning, numbness and other abnormal sensations), the Hamburg Pain Adjective List and the Neuropathy Disability Score. There were no reported adverse reactions.

Diabet Med. 1999 Dec;16(12):1040-3.
Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy.
Ruhnau KJ, Meissner HP, Finn JR, Reljanovic M, Lobisch M, Schutte K, Nehrdich D, Tritschler HJ, Mehnert H, Ziegler D.

6. This review indicates that different dosing methods of alpha-lipoic acid (600 mg/day intravenously for 3 weeks or 1800 mg/day orally for 3 weeks) have both been shown to improve diabetic polyneuropathy.

Exp Clin Endocrinol Diabetes. 1999;107(7):421-30.
Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials.
Ziegler D, Reljanovic M, Mehnert H, Gries FA.

7. Different doses of alpha-lipoic acid (600 mg, 1, 2 or 3 times/day) all increased insulin sensitivity in patients with Type 2 diabetes compared to the placebo group.

Free Radic Biol Med. 1999 Aug;27(3-4):309-14.
Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.
Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K.

8. Daily doses of alpha-lipoic acid (600/mg for 3 months) effectively decreased oxidative stress in patients with poor glycemic control and albuminuria.

Free Radic Biol Med. 1999 Jun;26(11-12):1495-500.
alpha-Lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria.
Borcea V, Nourooz-Zadeh J, Wolff SP, Klevesath M, Hofmann M, Urich H, Wahl P, Ziegler R, Tritschler H, Halliwell B, Nawroth PP.

9. Daily intravenous doses of alpha-lipoic acid (600 mg) improved the neurovascular reflex arc in diabetic patients with polyneuropathy by improving microcirculation and decreasing capillary blood cell velocity.

Microvasc Res. 1999 Jul;58(1):28-34.
The effect of alpha-lipoic acid on the neurovascular reflex arc in patients with diabetic neuropathy assessed by capillary microscopy.
Haak ES, Usadel KH, Kohleisen M, Yilmaz A, Kusterer K, Haak T.

10. Oral doses of alpha-lipoic acid (600 mg/twice/day) improved glucose effectiveness and prevented an increase in lactate and pyruvate levels in patients with Type 2 diabetes.

Diabetes Care. 1999 Feb;22(2):280-7.
alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.
Konrad T, Vicini P, Kusterer K, Hoflich A, Assadkhani A, Bohles HJ, Sewell A, Tritschler HJ, Cobelli C, Usadel KH.

11. Oxidative stress in diabetic patients activates NF-kappaB activity and is an indicator of diabetes related complications. Daily oral doses of alpha-lipoic acid (600 mg) reduced oxidative stress in patients with diabetic neuropathy.

Diabetologia. 1999 Feb;42(2):222-32.
Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the Oxidative-stress sensitive transcription factor NF-kappaB.
Hofmann MA, Schiekofer S, Isermann B, Kanitz M, Henkels M, Joswig M, Treusch A, Morcos M, Weiss T, Borcea V, Abdel Khalek AK, Amiral J, Tritschler H, Ritz E, Wahl P, Ziegler R, Bierhaus A, Nawroth PP.

12. A daily oral dose of alpha-lipoic acid (600 mg for 2 weeks) reduced the factor nuclear factor-kappa B (NF-kappa B) activity from oxidative stress, which contributes to complications in diabetic patients.

Diabetes Care. 1998 Aug;21(8):1310-6.
Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 Diabetes.
Hofmann MA, Schiekofer S, Kanitz M, Klevesath MS, Joswig M, Lee V, Morcos M, Tritschler H, Ziegler R, Wahl P, Bierhaus A, Nawroth PP.

13. Intravenous doses of alpha-lipoic acid (600 mg/day for 3 weeks) decreased foot pain, burning and numbness in patients with diabetic neuropathy compared to placebo. A daily oral dose of alpha-lipoic acid (800 mg for 4 months) reduced cardiac autonomic dysfunction in patients with non-insulin dependent diabetes.

Diabetes. 1997 Sep;46 Suppl 2:S62-6.
Alpha-lipoic acid in the treatment of Diabetic peripheral and cardiac autonomic neuropathy.
Ziegler D, Gries FA.

14. Treatment with alpha-lipoic acid (800 mg/day for 4 months) improved cardiac autonomic neuropathy in patients with non-insulin dependent diabetes without side effects.

Diabetes Care. 1997 Mar;20(3):369-73.
Comment in:
Diabetes Care. 1997 Dec;20(12):1918-20.
Effects of treatment with the antiOxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie.
Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G.

15. This pilot study showed that daily intravenous dose with alpha-lipoic acid (500 mg for 10 days) improved “resistance of insulin-stimulated glucose disposal” in patients with non-insulin dependent diabetes.

Exp Clin Endocrinol Diabetes. 1996;104(3):284-8.
Improvement of insulin-stimulated glucose-disposal in type 2 Diabetes after repeated parenteral administration of thioctic acid.
Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ.

16. Daily intravenous doses of alpha-lipoic acid (600 mg for 3 weeks) effectively reduced symptoms associated with peripheral neuropathy (pain, burning, numbness) in patients with non-insulin dependent diabetes.

Diabetologia. 1995 Dec;38(12):1425-33.
Treatment of symptomatic Diabetic peripheral neuropathy with the anti-Oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study).
Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA.

17. This study was the first to demonstrate that intravenous alpha-lipoic acid (1000 mg) increases insulin stimulated glucose disposal in patients with type 2 diabetes.

Arzneimittelforschung. 1995 Aug;45(8):872-4.
Enhancement of glucose disposal in patients with type 2 Diabetes by alpha-lipoic acid.
Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, Jung WI, Augustin HJ, Dietze GJ.

18. Different doses of alpha-lipoic acid (600 mg, 1, 2 or 3 times/day) all increased
insulin-stimulated glucose disposal (MCR) and insulin sensitivity in patients with type 2 diabetes compared to the placebo group.

Free Radic Biol Med 1999 Aug;27(3-4):309-14
Oral administration of RAC-alpha-lipoic acid modulates Insulin sensitivity in patients with type-2 Diabetes mellitus: a placebo-controlled pilot trial.
Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K.

19. Oral doses of alpha-lipoic acid (600 mg/twice/day) for 4 weeks significantly reduced
lactate and pyruvate levels in patients with type 2 diabetes.

Diabetes Care 1999 Feb;22(2):280-7
alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 Diabetes.
Konrad T, Vicini P, Kusterer K, Hoflich A, Assadkhani A, Bohles HJ, Sewell A, Tritschler HJ, Cobelli C, Usadel KH.
Department of Internal Medicine, J.W. Goethe-University, Frankfurt, Germany.

Bilberry

20. Treatment with anthocyanosides (found in bilberry) (600 mg/day for 2 months) helps prevent injury caused increased synthesis in connective tissue, which can lead to eye disease in diabetics.

Klin Monatsbl Augenheilkd. 1996 Dec;209(6):368-72.
[Effect of anthocyanins on human connective tissue metabolism in the human]
[Article in German]
Boniface R, Robert AM.

BIOTIN
(1 gram = 1000 milligrams)

21. A dose of intravenous biotin (75 grams) normalized the oral glucose tolerance test in hemodialysis patients.

Oral glucose tolerance test after highdose i.v. biotin administration in normoglucemic hemodialysis patients
Koutsikos D.; Fourtounas C.; Kapetanaki A.; Agroyannis B.; Tzanatos H.; Rammos G.; Kopelias I.; Bosiolis B.; Bovoleti O.; Darema M.; Sallum G.

22. A daily dose of biotin (9 mg) improved hyperglycemia without changing insulin levels in patients with non-insulin dependent diabetes. Treatment also decreased pyruvate and lactate levels to normal, improving glucose metabolism without side effects.

Journal of Clinical Biochemistry and Nutrition 1993 14 ( 3 ): p 2112-18
Biotin for diabetic peripheral neuropathy with noninsulin dependent diabetes mellitus.
Maebashi Masaru; Makino Yoshio; Furukawa Yuji(a); Ohinata Kosaku; Kimura Shuichi; Sato Takao Lab. Nutr., Dep. Appl. Biol. Chem., Fac. Agric., Tohoku Univ., Aobaku, Sendai 981

CHROMIUM
(1 microgram = 0.001 milligrams)

23. Daily doses of chromium (less that 1000 micrograms) may be effective in reducing glucose levels in hyperglycemia.

Ann Pharmacother. 2003 Jun;37(6):876-85.
Chromium as adjunctive treatment for type 2 diabetes.
Ryan GJ, Wanko NS, Redman AR, Cook CB.
PMID: 12773078

Animal Study

24. Treatment with chromium (20 micrograms per kilogram body mass for 24 weeks) reduced levels of LDL cholesterol; total cholesterol, triglycerides and insulin in type 2 diabetic rats.

J Biol Inorg Chem. 2002 Sep;7(7-8):852-62. Epub 2002 Apr 19.
The biomimetic [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+ )decreases plasma insulin, cholesterol, and triglycerides in healthy and type II diabetic rats but not type I diabetic rats.
Sun Y, Clodfelder BJ, Shute AA, Irvin T, Vincent JB.
PMID: 12203022

25. Daily doses of chromium picolinate (200 micrograms 3 times/day for 3 months) reduced glycosylated hemoglobin levels in a patient with type 1 diabetes.

J Fam Pract. 1998 Jan;46(1):83-6.
Chromium picolinate supplementation for diabetes mellitus.
Fox GN, Sabovic Z.
PMID: 9451374

26. Daily doses of chromium (200 micrograms/day) reduced insulin, and antidiabetic drug (sulfonylurea or metformin) requirements in patients with non-insulin dependent and insulin dependent diabetes.

Harefuah. 1993 Sep;125(5-6):142-5, 191.
[Chromium in the treatment of clinical diabetes mellitus]
[Article in Hebrew]
Ravina A, Slezack L.
PMID: 8225092

27. Compared to placebo, doses of chromium (200 micrograms twice/day for 12 weeks) improved glycemic control in patients with type 2 diabetes.

J Nutr Biochem. 2002 Nov;13(11):690-697.
Role of chromium supplementation in Indians with type 2 diabetes mellitus.
Ghosh D, Bhattacharya B, Mukherjee B, Manna B, Sinha M, Chowdhury J, Chowdhury S.
PMID: 12550067

28. Treatment with chromium (400 micrograms/day) and zinc (30 mg/day) for 6 months had antioxidant effects without side effects in people with type 2 diabetes.

J Am Coll Nutr. 2001 Jun;20(3):212-8.
Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus.
Anderson RA, Roussel AM, Zouari N, Mahjoub S, Matheau JM, Kerkeni A.
PMID: 11444416

29. According to this review, chromium supplements (200 micrograms/day) improve glucose levels in people with glucose intolerance. More than 200 micrograms/day may be required for those with diabetes and abnormal glucose tolerance. Daily chromium intake of 8 micrograms was more effective than 4 micrograms in women with gestational diabetes.

J Am Coll Nutr. 1998 Dec;17(6):548-55.
Chromium, glucose intolerance and diabetes.
Anderson RA.
PMID: 9853533

30. Doses of chromium (100 micrograms/day) decreased total plasma cholesterol after 4 months in addition to improving HbA1c values and lowering fasting glucose levels in patients with type 2 diabetes.

Diabetes. 1997 Nov;46(11):1786-91.
Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes.
Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, Feng J.
PMID: 9356027

31. Higher doses of chromium (500 micrograms/twice/day) were more effective in improving the glucose/insulin system than lower doses of chromium (100 micrograms/twice/day).

J Am Coll Nutr. 1997 Oct;16(5):404-10.
Nutritional factors influencing the glucose/insulin system: chromium.
Anderson RA.
PMID: 9322187

32. It is suggested that most dietary intakes of chromium are far below the minimum suggested intake of 50 micrograms/day.

Sci Total Environ. 1989 Oct 1;86(1-2):75-81.
Essentiality of chromium in humans.
Anderson RA.
PMID: 2602941

33. Compared to placebo, two doses of chromium (23 micrograms in brewers yeast and 200 micrograms oral supplement for 8 weeks) both had significant effects on decreasing glucose, fructosamine and triglycerides and increasing HDL.

Saudi Med J. 2000 Sep;21(9):831-7.
The effects of inorganic chromium and brewer's yeast supplementation on glucose tolerance, serum lipids and drug dosage in individuals with type 2 diabetes.
Bahijiri SM, Mira SA, Mufti AM, Ajabnoor MA.
PMID: 11376359

34. Daily doses of chromium (1000 micrograms/day) were found to alleviate many symptoms associated with type 2 diabetes.

Curr Opin Clin Nutr Metab Care. 1998 Nov;1(6):509-12.
Comment in:
Curr Opin Clin Nutr Metab Care. 1998 Nov;1(6):487-9.
Chromium update: examining recent literature 1997-1998.
Preuss HG, Anderson RA.
PMID: 10565402

GREEN TEA

35. A dose of green tea polyphenols (GTP) (100 mg per kilogram body weight) significantly reduced blood glucose levels in diabetic rats

J Ethnopharmacol. 2002 Nov;83(1-2):109-16.
Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes.
M C S, K S, Kuttan R.

MILK THISTLE/SILYMARIN/SILYBIN

36. Treatment with silybin (135 mg/day orally for 6 months) reduced glucose levels and triglycerides in patients with alcoholic liver disease and type 2 diabetes.

Dabetes Nutr Metab. 2002 Aug;15(4):222-31.
Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent.
Lirussi F, Beccarello A, Zanette G, De Monte A, Donadon V, Velussi M, Crepaldi G.

N-ACETYLCYSTEINE
Animal Study

37. A single dose of N-acetylcysteine (200 or 1000 mg per kilogram body weight) arrested the development of tumor necrosis factor in diabetic rats, which may have implications in preventing diabetes related complications.

Clin Immunol Immunopathol. 1994 Jun;71(3):333-7.
Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats.
Sagara M, Satoh J, Zhu XP, Takahashi K, Fukuzawa M, Muto G, Muto Y, Toyota T.

SELENIUM
Animal Study

38. A diet of taurine (5%), vitamin E (500 IU per kilogram diet) and selenium (8 mg per kilogram diet) for 4 month significantly reduced lipid hydroperoxides and retinopathy in diabetic rats

Free Radic Res. 2003 Mar;37(3):323-30.
Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations.
Di Leo MA, Ghirlanda G, Gentiloni Silveri N, Giardina B, Franconi F, Santini SA.
PMID: 12688428

Animal Study

39. Dosages of vitamin E (20 mg over 24 hours) and selenium (0.3 mg over 24 hours) for 25 days together provide significant protection against oxidative damage in muscle, liver and blood in diabetic rats compared to placebo or each supplement on its own.

Biol Trace Elem Res. 2001 Feb;79(2):149-59.
Protective role of intraperitoneally administered vitamin E and selenium on the antioxidative defense mechanisms in rats with diabetes induced by streptozotocin.
Naziroglu M, Cay M.
PMID: 11330521

Animal Study
(1 micromole = one-thousandth of a gram-molecule)

40. A diet supplemented with selenium (0.99 micromoles per 100 grams of diet) and vitamin E (0.145 micromole per 100 grams of diet) for 24 weeks decreased blood glucose levels and protected the kidneys in diabetic rats compared to placebo or each supplement on its own.

Proc Soc Exp Biol Med. 1996 Apr;211(4):323-31.
A selenium supplement associated or not with vitamin E delays early renal lesions in experimental diabetes in rats.
Douillet C, Tabib A, Bost M, Accominotti M, Borson-Chazot F, Ciavatti M.
PMID: 8618937

41. The antioxidants alpha-lipoic acid (600 mg) or selenium (100 micrograms) or vitamin E (1200 IU) each protected diabetic patients from oxidative stress compared to the control group.

Z Gesamte Inn Med. 1993 May;48(5):223-32.
[Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation]
[Article in German]
Kahler W, Kuklinski B, Ruhlmann C, Plotz C.
PMID: 8390768

VITAMIN B1/THIAMINE

42. Supplementation with Milgamma (a combination of 50 mg vitamin B1 and 0.35 mg vitamin B12) for 3 months was more effective in reducing symptoms of painful polyneuropathy in diabetic patients than conventional vitamin B complex.

Folia Med (Plovdiv). 1997;39(4):5-10.
Therapeutic efficacy of "Milgamma" in patients with painful diabetic neuropathy.
Simeonov S, Pavlova M, Mitkov M, Mincheva L, Troev D.

Cell Study

43. Red blood cells were treated with thiamine (50 – 500 micromoles), which prevented biochemical changes in the cells that indicate diabetic complications. Thus, thiamine may help prevent complications in diabetics.

J Biochem (Tokyo). 2001 Apr;129(4):543-9.
Suppression of the accumulation of triosephosphates and increased formation of methylglyoxal in human red blood cells during hyperglycaemia by thiamine in vitro.
Thornalley PJ, Jahan I, Ng R.

Cell Study

44. Human arterial smooth muscle cells (ASMC) from diabetic patients are linked to the advancement of atherosclerosis as high insulin and glucose levels have an effect on their proliferation. Cells treated with thiamine (200 micromoles), which restricted the proliferation of the cells. Thus, thiamine may arrest the development of atherosclerosis in diabetics.

Ann Vasc Surg. 2000 Jan;14(1):37-43.
Thiamine (Vitamin B1) protects against glucose- and insulin-mediated proliferation of human infragenicular arterial smooth muscle cells.
Avena R, Arora S, Carmody BJ, Cosby K, Sidawy AN.

Cell Study

45. Human cell replication is impaired by glucose but the addition of thiamine or benfotiamine (150 micromoles) corrected this problem. Thus, thiamine may be important in dealing with vascular complications in diabetics.

Acta Diabetol. 2001;38(3):135-8.
Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose.
Pomero F, Molinar Min A, La Selva M, Allione A, Molinatti GM, Porta M.

Cell Study

46. Treatment of human cells with thiamine (150 micromoles) prevented biochemical changes, which lead to complications in diabetes.

47. Doses of thiamine (25 mg/day) and pyridoxine (50 mg/day) for 4 weeks reduced symptoms of peripheral neuropathy by 49% in diabetic patients whereas doses of 1 mg/day of each supplement reduced symptoms by only 11%.

East Afr Med J. 1997 Dec;74(12):803-8.
Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy.
Abbas ZG, Swai AB.

VITAMIN B3/NIACIN/NICOTINAMIDE

Animal Study

48. An injected dose of nicotinamide (500 mg per kilogram body weight) protected the animals from the toxic effect of the drug streptozotocin.

J Ayub Med Coll Abbottabad. 2001 Jul-Sep;13(3):26-30.
The optimum dose of nicotinamide for protection of pancreatic beta-cells against the cytotoxic effect of streptozotocin in albino rat.
Hassan N, Janjua MZ.
PMID: 11873395

49. Doses of nicotinamide (25 mg per kilogram body weight) are as effective as 50 mg per kilogram body weight in improving beta cell functioning in type 1 diabetics after 1 year. Patients receiving the higher dose of nicotinamide tended to have a higher insulin dosage.

Diabetes Metab Res Rev. 1999 May-Jun;15(3):181-5.
A multi-centre randomized trial of two different doses of nicotinamide in patients with recent-onset type 1 diabetes (the IMDIAB VI).
Visalli N, Cavallo MG, Signore A, Baroni MG, Buzzetti R, Fioriti E, Mesturino C, Fiori R, Lucentini L, Matteoli MC, Crino A, Corbi S, Spera S, Teodonio C, Paci F, Amoretti R, Pisano L, Suraci C, Multari G, Sulli N, Cervoni M, De Mattia G, Faldetta MR, Boscherini B, Pozzilli P, et al.
PMID: 10441040

Animal Study

50. Compared to placebo and insulin, doses of nicotinamide (0.5 grams/3 times/day) added to doses of insulin or sulphonylureas improved C-peptide release in type 2 diabetics.

Acta Diabetol. 1998 Apr;35(1):61-4.
Nicotinamide improves insulin secretion and metabolic control in lean type 2 diabetic patients with secondary failure to sulphonylureas.
Polo V, Saibene A, Pontiroli AE.
PMID: 9625292

51. Daily doses of nicotinamide (25 mg per kilogram body weight) or vitamin E (15 mg per kilogram body weight) for 1 year each protected beta cell functioning in a similar fashion when added to insulin treatment.

Eur J Endocrinol. 1997 Sep;137(3):234-9.
Erratum in:
Eur J Endocrinol 1997 Nov;137(5):558. Suraci MT[corrected to Suraci C]
Vitamin E and nicotinamide have similar effects in maintaining residual beta cell function in recent onset insulin-dependent diabetes (the IMDIAB IV study)
Pozzilli P, Visalli N, Cavallo MG, Signore A, Baroni MG, Buzzetti R, Fioriti E, Mesturino C, Fiori R, Romiti A, Giovannini C, Lucentini L, Matteoli MC, Crino A, Teodonio C, Paci F, Amoretti R, Pisano L, Suraci C, Multari G, Suppa M, Sulli N, De Mattia G, Faldetta MR, Suraci MT.
PMID: 9330586

Animal Study

52. Diabetic mice were treated with nicotinamide (500 mg per kilogram body weight/day) from the age of 4 to 8 weeks. All mice that were not treated with nicotinamide (control group) developed diabetes and did so at an earlier age than the 29% of treated mice that developed diabetes.

J Korean Med Sci. 1997 Aug;12(4):293-7.
Inhibition of diabetes in non-obese diabetic mice by nicotinamide treatment for 5 weeks at the early age.
Kim JY, Chi JK, Kim EJ, Park SY, Kim YW, Lee SK.
PMID: 9288627

Animal Study

53. Rats were given nicotinamide (1 gram per kilogram body weight/day) either orally or injected, before and after inducing diabetes. In the rats treated with nicotinamide, fasting blood glucose and urinary glucose excretion were near normal while the untreated rats remained hyperglycemic. Thus, nicotinamide may help prevent insulin dependent diabetes if treated early.

Chin Med J (Engl). 1996 Nov;109(11):819-22.
Effects of nicotinamide on prevention and treatment of streptozotocin-induced diabetes mellitus in rats.
Hu Y, Wang Y, Wang L, Zhang H, Zhang H, Zhao B, Zhang A, Li Y.
PMID: 9275363

54. A daily dose of nicotinamide (2 grams) for 2 weeks decreased insulin sensitivity in patients with a positive islet cell antibody score.

Diabetes. 1996 Nov;45(11):1631-4.
Nicotinamide's effects on glucose metabolism in subjects at risk for IDDM.
Greenbaum CJ, Kahn SE, Palmer JP.
PMID: 8866571

Animal Study

55. Treatment with nicotinamide (0.5 grams per kilogram body weight/day) improved hyperglycemia in diabetic rats after isogenic islet transplant compared to those without nicotinamide supplement.

Transplantation. 1995 Aug 27;60(4):313-7.
The amelioration of hyperglycemia in streptozotocin-induced diabetic rats after the intraportal transplantation of an insufficient number of islets by nicotinamide treatment.
Ueki M, Yasunami Y, Motoyama K, Funakoshi A, Ikeda S, Tanaka M.
PMID: 7652756

56. Treatment with nicotinamide (25 mg per kilogram body weight) in addition to regular insulin treatment improved beta cell function without side effect, mostly in patients that had been diagnosed after 15 years of age.

Diabetologia. 1995 Jul;38(7):848-52.
Double blind trial of nicotinamide in recent-onset IDDM (the IMDIAB III study).
Pozzilli P, Visalli N, Signore A, Baroni MG, Buzzetti R, Cavallo MG, Boccuni ML, Fava D, Gragnoli C, Andreani D, et al.
PMID: 7556988

57. Treatment with nicotinamide (25 mg per kilogram body weight) in patients at high risk for developing insulin dependent diabetes increased insulin secretion and repaired beta cell functioning as compared with those not treated with nicotinamide.

Br J Clin Pract. 1992 Autumn;46(3):177-9.
Nicotinamide treatment in subjects at high risk of developing IDDM improves insulin secretion.
Manna R, Migliore A, Martin LS, Ferrara E, Ponte E, Marietti G, Scuderi F,
Cristiano G, Ghirlanda G, Gambassi G.
PMID: 1286017

58. Treatment with nicotinamide (1 gram/day) for 45 days increased C peptide secretion in newly diagnosed patients with insulin dependent diabetes compared to those not treated with nicotinamide.

Diabetologia. 1989 Mar;32(3):160-2.
Effect of nicotinamide therapy upon B-cell function in newly diagnosed type 1 (insulin-dependent) diabetic patients.
Mendola G, Casamitjana R, Gomis R.
PMID: 2526767

Animal Study

59. Treatment with injected nicotinamide (0.5 mg per gram body weight/day) for 40 days returned glucose tolerance to normal in diabetic mice compared to untreated animals, which developed severe insulitis and glycosuria. Nicotinamide may also repair B-cell damage in early stages of insulin dependent diabetes.

Diabetes. 1982 Sep;31(9):749-53.
Preventive and therapeutic effects of large-dose nicotinamide injections on diabetes associated with insulitis. An observation in nonobese diabetic (NOD) mice.
Yamada K, Nonaka K, Hanafusa T, Miyazaki A, Toyoshima H, Tarui S.
PMID: 6219022

VITAMIN B6/PYRIDOXINE

60. Treatment with pyridoxine (150 mg/day) for 6 weeks reduced glycosylated hemoglobin (HbA1c) levels in patients with type 2 diabetes compared to control group. The HbA1c levels increased again when given placebo.

Diabetes. 1989 Jul;38(7):881-6.
Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus.
Solomon LR, Cohen K.
PMID: 2737364

VITAMIN C
(1 gram = 1000 milligrams)

61. Treatment with vitamin C (1.0 gram/day) in conjunction with insulin treatment may improve endothelial dysfunction and oxidative stress in patients with type 2 diabetes. The benefits of insulin treatment may also be increased by vitamin C.

Eur J Clin Invest. 2003 Mar;33(3):231-8.
Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus.
Evans M, Anderson RA, Smith JC, Khan N, Graham JM, Thomas AW, Morris K, Deely D, Frenneaux MP, Davies JS, Rees A.

62. Treatment with vitamin C (0.5 grams/twice/day) for 4 months decreased insulin, LDL and triglyceride levels as well as plasma free radicals in patients with type 2 diabetes. Thus, vitamin C is of benefit to glucose and lipid metabolism in type 2 diabetes.

J Am Coll Nutr. 1995 Aug;14(4):387-92
Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics.
Paolisso G, Balbi V, Volpe C, Varricchio G, Gambardella A, Saccomanno F, Ammendola S, Varricchio M, D'Onofrio F.

63. Treatment with vitamin C (1 gram/day for 6 weeks) reduced oxidative stress and improved endothelial function in patients with type 2 diabetes.

Eur J Clin Invest. 2003 Mar;33(3):231-8
Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus.
Evans M, Anderson RA, Smith JC, Khan N, Graham JM, Thomas AW, Morris K, Deely D, Frenneaux MP, Davies JS, Rees A.

64. Treatment with vitamin C (1000 mg/day) and vitamin E (800 IU/day) for 6 months improved endothelium-dependent vasodilation in patients with type 1 diabetes.

Am J Physiol Heart Circ Physiol. 2003 Jul 24 [Epub ahead of print].
Oral Antioxidant Therapy Improves Endothelial Function in Type 1 but not Type 2 Diabetes Mellitus.
Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Keaney JF, Creager MA.

65. Treatment with vitamin C (1000 mg/day) and vitamin E (400 IU/day) for 10 days reduced oxidative stress and free radical production in patients with type 2 diabetes.

Br J Ophthalmol. 2002 Dec;86(12):1369-73
Protective role of oral antioxidant supplementation in ocular surface of diabetic patients.
Peponis V, Papathanasiou M, Kapranou A, Magkou C, Tyligada A, Melidonis A, Drosos T, Sitaras NM.

66. Treatment with vitamin C (500 mg/day) for 4 weeks reduced arterial blood pressure and stiffness in patients with type 2 diabetes, thus reducing the risk of cardiovascular disease common in diabetes.

Hypertension. 2002 Dec;40(6):804-9.
Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes.
Mullan BA, Young IS, Fee H, McCance DR.

67. Treatment with vitamin C (500 mg/day) for 12 months reduced cholesterol and triglycerides in patients with type 2 diabetes.

Int J Vitam Nutr Res. 1978;48(4):368-73
Hypocholesterolemic effect of ascorbic acid in maturity-onset diabetes mellitus.
Ginter E, Zdichynec B, Holzerova O, Ticha E, Kobza R, Koziakova M, Cerna O, Ozdin L, Hruba F, Novakova V, Sasko E, Gaher M
PMID: 367979

VITAMIN D
(1 microgram = 0.001 milligrams)

68. A daily dose of vitamin D (50 micrograms) during the first year may decrease risk of type 1 diabetes in infants.

Nutr Rev. 2002 Apr;60(4):118-21.
Can vitamin D supplementation in infancy prevent type 1 diabetes?
Harris S.
PMID: 12002683

69. A daily dose of vitamin D (2000 IU) was associated with a lowered risk of type 1 diabetes developing in children.

Lancet. 2001 Nov 3;358(9292):1500-3.
Comment in:
    Lancet. 2001 Nov 3;358(9292):1476-8.
    Lancet. 2002 Apr 6;359(9313):1246-7; discussion 1247-8.
    Lancet. 2002 Apr 6;359(9313):1246; discussion 1247-8.
    Lancet. 2002 Apr 6;359(9313):1247; discussion 1247-8.
    Lancet. 2002 Apr 6;359(9313):1248.
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study.
Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM.
PMID: 11705562

70. A daily dose of vitamin D (0.05 micrograms per kilogram body weight) for 1 year corrected bone loss in children with insulin dependent diabetes.

Eur J Pediatr. 1996 Jan;155(1):15-7.
Treatment of osteopenia in children with insulin-dependent diabetes mellitus: the effect of 1 alpha-hydroxyvitamin D3.
Al-Qadreh A, Voskaki I, Kassiou C, Athanasopoulou H, Sarafidou E, Bartsocas CS.
PMID: 8750803

VITAMIN E/TOCOTRIENOL

71. A daily dose of vitamin E (1200 IU) for 4 months decreased microalbuminemia in patients with diabetic nephropathy.

Vnitr Lek. 2003 Jul;49(7):529-34.
[Effect of vitamin E therapy on progression of diabetic nephropathy]
[Article in Slovak]
Hirnerova E, Krahulec B, Strbova L, Stecova A, Dekret J, Hajovska A.
PMID: 12931434

Animal Study

72. Daily doses of vitamin E (250 IU/3 times/day) improve lipoprotein peroxidizability and therefore should be considered in treatment of people with type 1 diabetes.

Am J Clin Nutr. 2000 Nov;72(5):1142-9.
Effects of long-term supplementation with moderate pharmacologic doses of vitamin E are saturable and reversible in patients with type 1 diabetes.
Engelen W, Keenoy BM, Vertommen J, De Leeuw I.
PMID: 11063441

73. Daily doses of vitamin E (1000 IU/day for 3 months) improves endothelial vasodilator
function in people with type 1 diabetes.

J Am Coll Cardiol. 2000 Jul;36(1):94-102.
Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study.
Skyrme-Jones RA, O'Brien RC, Berry KL, Meredith IT.
PMID: 10898419

74. Daily doses of vitamin E (800 IU/day) provide antioxidant protection in type 2 diabetes.

Horm Metab Res. 1999 Dec;31(12):665-71.
High dose supplementation of RRR-alpha-tocopherol decreases cellular hemostasis but accelerates plasmatic coagulation in type 2 diabetes mellitus.
Ferber P, Moll K, Koschinsky T, Rosen P, Susanto F, Schwippert B, Tschope D.
PMID: 10668920

75. Compared to placebo, daily doses of vitamin E (1800 IU/day) for 4 months improved renal function and may reduce diabetic nephropathy and retinopathy.

Diabetes Care. 1999 Aug;22(8):1245-51.
Comment in:
Diabetes Care. 1999 Aug;22(8):1242-4.
High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes.
Bursell SE, Clermont AC, Aiello LP, Aiello LM, Schlossman DK, Feener EP, Laffel
L, King GL.
PMID: 10480765

76. Daily doses of vitamin E (1200 IU/day) for 8 weeks reduced LDL oxidizability in patients with type 2 diabetes.

Am J Clin Nutr. 1996 May;63(5):753-9.
RRR-alpha-tocopheryl acetate supplementation at pharmacologic doses decreases low-density-lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus.
Fuller CJ, Chandalia M, Garg A, Grundy SM, Jialal I.
PMID: 8615360

77. Compared to placebo, supplementation with vitamin E (100 IU/day for 3 months) reduced lipid peroxidation in patients with diabetes.

Lipids. 1996 Mar;31 Suppl:S87-90.
The effect of modest vitamin E supplementation on lipid peroxidation products and other cardiovascular risk factors in diabetic patients.
Jain SK, McVie R, Jaramillo JJ, Palmer M, Smith T, Meachum ZD, Little RL.
PMID: 8729100

VITAMIN K
Animal Study

78. A dose of vitamin K (10 – 100 mg per kilogram body weight) increased the pain threshold in diabetic mice.

Jpn J Pharmacol. 2001 Mar;85(3):335-7.
Antinociceptive effect of Vitamin K2 (menatetrenone) in diabetic mice.
Onodera K, Zushida K, Kamei J.
PMID: 11325029

PYCNOGENOL
Animal Study

79. Treatment with pycnogenol (10 mg per kilogram body weight for 14 days) significantly reduced blood glucose levels in diabetic rats.

J Biochem Mol Toxicol. 2003;17(3):193-9.
Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats.
Maritim A, Dene BA, Sanders RA, Watkins JB 3rd.

80. Treatment with pycnogenol (50 mg/ 3 times/day for 2 months) halted the progression of retinopathy (showed increase in visual acuity and no retinal function deterioration) while retinopathy worsened in the placebo group.

Phytother Res. 2001 May;15(3):219-23.
Treatment of vascular retinopathies with Pycnogenol.
Spadea L, Balestrazzi E.