Vitamins that may be helpful
A variety of vitamins, minerals, amino acids, and other supplements may help with symptoms
and deficiencies associated with diabetes. However, many of the studies described below were
done in adults, and the amounts used may not be appropriate for a child with type 1 diabetes.
The proper amount of each nutrient to be used by a child should always be discussed with a
doctor.
Alpha lipoic acid
Alpha lipoic acid is a powerful natural
antioxidant. Preliminary and double-blind trials have found that supplementing with 600 to
1,200 mg of lipoic acid per day improves the symptoms of diabetic nerve damage
(neuropathy).57 58 59 60 In a preliminary study,
supplementing with 600 mg of alpha-lipoic acid per day for 18 months slowed the progression of
kidney damage in people with type 1 diabetes.61
Chromium
Chromium, a trace mineral that appears to increase the effectiveness of insulin, has been
shown to improve glucose and related variables in people with many kinds of diabetes,
including type 1 diabetes.62 63 Chromium may also lower levels of total
cholesterol, LDL cholesterol, and triglycerides (risk factors for heart disease).64 65 The typical
amount of chromium used in research trials is 200 mcg per day. Supplementation with chromium
or brewer’s yeast (a source of chromium)
could potentially enhance the effects of drugs for diabetes (e.g., insulin or other blood
sugar-lowering agents) and possibly lead to
hypoglycemia. Therefore, people with diabetes taking these medications should supplement
with chromium or brewer's yeast only under the supervision of a doctor.
Magnesium
People with type 1 diabetes tend to have low magnesium levels, and magnesium given orally
or by injection partially overcomes the reduction in magnesium levels.66 In one
preliminary trial, insulin requirements were
lower in people with type 1 diabetes who were given magnesium.67 Diabetes-induced
damage to the eyes is more likely to occur in magnesium-deficient people with type 1
diabetes.68 In magnesium-deficient
pregnant women with type 1 diabetes, the lack of magnesium may even account for the high
rate of spontaneous abortion and birth defects
associated with type 1 diabetes.69 A double-blind trial found that giving 300 mg
per day of magnesium to magnesium-deficient type 1 diabetics for five years slowed the
development of diabetic nerve damage (neuropathy). The American Diabetes Association
acknowledges strong associations between magnesium deficiency and insulin resistance but has
not said magnesium deficiency is a risk factor.70 Many doctors, however, recommend
that adults with diabetes and normal kidney function supplement with 200 to 600 mg of
magnesium per day (those amounts would be lower for children).
Evening primrose oil
Supplementing with 4 grams of evening primrose oil per day for six months has been found in
double-blind research to improve nerve function and to relieve pain symptoms in people with
diabetic nerve damage (neuropathy).71
Acetyl-L-carnitine
In a double-blind study of people with diabetic nerve damage (neuropathy), supplementing
with acetyl-L-carnitine was significantly more effective than a placebo in improving
subjective symptoms of neuropathy and objective measures of nerve function.72
People who received 1,000 mg of acetyl-L-carnitine three times per day tended to fare better
than those who received 500 mg three times per day.
B Vitamins
Blood levels of vitamin B1 (thiamine) have
been found to be low in people with type 1 diabetes.73 A controlled trial in Africa
found that supplementing with both vitamin B1 (25 mg per day) and vitamin B6 (50 mg per day) led to significant
improvement of symptoms of diabetic nerve damage (neuropathy) after four weeks.74
However, since this was a trial conducted among people in a vitamin B1–deficient
developing country, these improvements might not occur in other people with diabetes. Another
trial found that combining vitamin B1 (in a special fat-soluble form) and vitamin B6 plus vitamin B12 in high but variable amounts led to
improvement in some aspects of diabetic neuropathy in 12 weeks.75 As a result, some
doctors recommend that people with diabetic neuropathy supplement with vitamin B1, though the
optimal level of intake remains unknown.
Taking large amounts of niacin (a form of
vitamin B3), such as 2 to 3 grams per day, may impair glucose tolerance and should be used by
people with diabetes only with medical supervision.76 77
Some clinical trials have shown that
niacinamide (another form of vitamin B3) supplementation might be useful in the very early
stages of type 1 diabetes,78 though not all trials support this claim.79
80 81 Although an analysis of research shows that niacinamide does help
preserve some function of insulin-secreting cells in people recently diagnosed with type 1
diabetes, the amount of insulin required for those given niacinamide has remained essentially
as high as for those given placebo.82 A controlled trial found no beneficial effect
of niacinamide supplementation (700 mg three times per day in addition to intensive insulin
therapy) on pancreatic function and glucose tolerance in people newly diagnosed with type 1
diabetes.83
Some,84 but not all,85 reports suggest that healthy children
at high risk for type 1 diabetes (such as the healthy siblings of children with type 1
diabetes) may be protected from the disease by supplementing with niacinamide. Parents of
children with type 1 diabetes should consult their doctor regarding niacinamide
supplementation as a way to prevent diabetes in their other children. Although the optimal
amount of niacinamide is not known, recent evidence suggests that 25 mg per 2.2 pounds of body
weight per day may be as effective as higher amounts.86
Many people with diabetes have low blood levels of vitamin B6.87 88 Levels are even
lower in people with diabetes who also have neuropathy.89 In a trial that included
people with type 1 diabetes, 1,800 mg per day of a special form of vitamin B6—pyridoxine
alpha-ketoglutarate—improved glucose tolerance dramatically.90 Vitamin B6 may
also reduce the amount of glycosylation, so taking adequate amounts of this vitamin may be
beneficial for all people with diabetes.91
Biotin is a B vitamin needed to process
glucose. When people with type 1 diabetes were given 16 mg of biotin per day for one week,
their fasting glucose levels dropped by 50%.92 Biotin may also reduce pain from
diabetic nerve damage (neuropathy).93 Some doctors try 16 mg of biotin for a few
weeks to see if blood sugar levels will fall.
Vitamin B12 is needed for normal
functioning of nerve cells. Vitamin B12 taken orally has reduced symptoms of nerve damage
caused by diabetes in 39% of people studied; when given both intravenously and orally,
two-thirds of people improved.94 In a preliminary trial, people with nerve damage
due to kidney disease or to diabetes plus kidney disease received intravenous injections of
500 mcg of methylcobalamin (the main form of vitamin B12 found in the blood) three times a day
for six months in addition to kidney dialysis. Nerve pain was significantly reduced and nerve
function significantly improved in those who received the injections.95 Oral
vitamin B12 up to 500 mcg three times per day is recommended by some practitioners.
L-carnitine
L-carnitine is an amino acid needed to
properly utilize fat for energy. When people with diabetes were given L-carnitine (0.5 mg per
2.2 pounds of body weight), high blood levels of fats—both cholesterol and triglycerides—dropped 25 to 39% in just ten days
in one trial.96
Vitamin C
People with type 1 diabetes appear to have low vitamin C levels.97 As with
vitamin E, vitamin C may reduce glycosylation.98 Vitamin C also lowers sorbitol
levels in people with diabetes.99 Sorbitol is a sugar that can accumulate inside
the cells and damage the eyes, nerves, and kidneys of people with diabetes. Vitamin C
supplementation (500 mg twice a day for one year) has significantly reduced urinary protein
loss in people with diabetes. Urinary protein loss (also called proteinuria) is associated
with poor prognosis in diabetes.100 Many doctors suggest that people with diabetes
supplement with 1 to 3 grams per day of vitamin C. Higher amounts could be problematic,
however. In one person, 4.5 grams per day was reported to increase blood sugar
levels.101
One study examined antioxidant supplement intake, including both vitamins E and C, and the
incidence of diabetic eye damage (retinopathy).102 A surprising finding was
that people with extensive retinopathy had a greater likelihood of having taken vitamin C and
vitamin E supplements. The outcome of this study, however, does not fit with most other
published data and might simply reflect the fact that sicker people are more likely to take
supplements in hopes of getting better. For the present, most doctors remain relatively
unconcerned about the outcome of this isolated report.
Vitamin D
Vitamin D is needed to maintain adequate blood levels of insulin.103 Vitamin D receptors have been
found in the pancreas where insulin is made and preliminary evidence suggests that
supplementation might reduce the risk of developing type 1 diabetes.104 Not enough
is known about optimal amounts of vitamin D for people with diabetes, and high amounts of
vitamin D can be toxic. Therefore, people with diabetes considering vitamin D supplementation
should talk with a doctor and have their vitamin D status assessed.
Vitamin E
People with low blood levels of vitamin E are more likely to develop type 1
diabetes,105 but no studies have been done using vitamin E supplements to try to
prevent type 1 diabetes. Animal and preliminary human data indicate that vitamin E
supplementation may protect against diabetic eye damage (retinopathy) and nephropathy,106
107 serious complications of diabetes involving the eyes and kidneys, respectively,
though no long-term trials in humans have confirmed this preliminary evidence. Glycosylation
is an important measurement of diabetes; it refers to how much sugar attaches abnormally to
proteins. Excessive glycosylation appears to be one of the causes of the organ damage that
occurs in diabetes. Vitamin E supplementation has reduced the amount of glycosylation in
many,108 109 110 although not all,111
112 studies of people with type 1 diabetes.
Zinc
People with type 1 diabetes tend to be zinc deficient,113 which may impair immune function.114 Zinc supplements
have lowered blood sugar levels in people with type 1 diabetes.115
Some doctors are concerned about having people with type 1 diabetes supplement with zinc
because of a report that zinc supplementation increased glycosylation,116 generally
a sign of deterioration of the condition. This trial is hard to evaluate because zinc
supplementation increases the life of blood cells and such an effect artificially increases
the lab test results for glycosylation. Until this issue is resolved, those with type 1
diabetes should consult a doctor before considering supplementation with zinc.
Antioxidants
Because oxidation damage is believed to play a role in the development of diabetic eye
damage (retinopathy), antioxidant nutrients
might be protective. One doctor has administered a daily regimen of 500 mcg selenium, 800 IU vitamin E, 10,000 IU vitamin A, and 1,000 mg vitamin C for several years to 20 people with diabetic
eye damage (retinopathy). During that time, 19
of the 20 people showed either improvement or no progression of their
retinopathy.117 People who wish to supplement with more than 250 mcg of selenium
per day should consult a healthcare practitioner.
Coenzyme Q10
Coenzyme Q10 (CoQ10) is needed for normal blood sugar metabolism. Animals with diabetes
have been reported to be CoQ10 deficient. In one trial, blood sugar levels fell substantially
in 31% of people with diabetes after they supplemented with 120 mg per day of CoQ7, a
substance similar to CoQ10.118 In people with type 1 diabetes, however,
supplementation with 100 mg of CoQ10 per day for three months neither improved glucose control
nor reduced the need for insulin.119 The importance of CoQ10 supplementation for
people with diabetes remains an unresolved issue, though some doctors recommend approximately
50 mg per day as a way to protect against possible effects associated with diabetes-induced
depletion.
Fish oil
Glucose tolerance improves in healthy people taking omega-3 fatty acid
supplements.120 And in one trial, people with diabetic nerve damage (neuropathy)
and diabetic nephropathy experienced significant improvement when given 600 mg three times per
day of purified eicosapentaenoic acid (EPA)—one of the two major omega-3 fatty acids
found in fish oil supplements—for 48 weeks.121 However, controlled studies
have found that fish oil supplementation increases cholesterol in people with type 1
diabetes.122 123 Until the risk–benefit ratio of using fish oil is
clarified, people with diabetes should feel free to increase their fish intake, but they
should consult a doctor before taking fish oil supplements.
Glucomannan
Glucomannan is a water-soluble dietary fiber derived from konjac root (Amorphophallus
konjac). Glucomannan delays stomach emptying, leading to a more gradual absorption of
dietary sugar. This effect can reduce the elevation of blood sugar levels that is typical
after a meal.124 This could lower insulin requirements for type 1 diabetics, but no
research has been done to test this possibility.
Inositol
Inositol is needed for normal nerve function. Diabetes can cause a type of nerve damage
known as diabetic neuropathy. Certain measures of the severity of this condition have been
reported to improve with inositol supplementation (500 mg taken twice per day);125
however, in other trials, inositol was ineffective.126
Manganese
People with diabetes may have low blood levels of manganese.127 Animal research
suggests that manganese deficiency can contribute to glucose intolerance and may be reversed
by supplementation.128 A young adult with insulin-dependent diabetes who received
oral manganese (3 to 5 mg per day as manganese chloride) reportedly experienced a significant
fall in blood glucose, sometimes to dangerously low levels. In three other people with type 1
diabetes, manganese supplementation had no effect on blood glucose levels.129
People with type 1 diabetes wishing to supplement with manganese should do so only with a
doctor’s close supervision.
Quercetin
Doctors have suggested that quercetin might help people with diabetes because of its
ability to reduce levels of sorbitol—a
sugar that accumulates in nerve cells, kidney cells, and cells within the eyes of people with
diabetes and has been linked to damage to those organs.130 Clinical trials have yet
to explore whether quercetin actually protects people with diabetes from nerve damage
(neuropathy), nephropathy, or eye damage (retinopathy).
Starch blockers
Starch blockers are substances that inhibit amylase, the digestive enzyme required to break
down dietary starches for normal absorption. Controlled research has demonstrated that
concentrated starch blocker extracts, when given with a starchy meal, can reduce the usual
rise in blood sugar levels of both healthy people and diabetics.131 132
133 134 135 While this effect could be helpful in controlling
diabetes, no research has investigated the long-term effects of taking starch blockers for
this condition.
Taurine
Taurine is an amino acid found in protein-rich food. People with type 1 diabetes have been
reported to have low blood taurine levels, a condition that increases the risk of heart
disease by altering blood viscosity. Supplementing with taurine (1.5 grams per day) has
restored blood taurine to normal levels and corrected the problem of blood viscosity within
three months.136
Vanadium
While vanadyl sulfate, a form of vanadium, may improve glucose control in people with type
2 diabetes,137 138 139 it may not help people with type 1
diabetes according to one preliminary report.140 The long-term safety of the large
amounts of vanadium used in diabetes research (typically 100 mg per day) remains unknown. Many
doctors expect that amounts this high may prove to be unsafe in the long term.
Are there any side effects or interactions?
Refer to the individual supplement for information about any side effects or interactions.
1. Wolever TMS, Brand Miller J. Sugars and blood glucose control. Am
J Clin Nutr 1995;62:212S–7S [review].
2. Wolever TMS, Brand Miller J. Sugars and blood glucose control. Am J
Clin Nutr 1995;62:212S–7S [review].
3. Brand-Miller J, Hayne S, Petocz P, Colagiuri S. Low-glycemic index
diets in the management of diabetes: a meta-analysis of randomized controlled trials.
Diabetes Care 2003;26:2466–8 [review].
4. Franz MJ. The glycemic index: not the most effective nutrition therapy
intervention. Diabetes Care 2003;26:2466–8 [review].
5. Colagiuri S, Miller JJ, Edwards RA. Metabolic effects of adding
sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus.
Am J Clin Nutr 1989;50:474–8.
6. Abraira C, Derler J. Large variations of sucrose in constant
carbohydrate diets in type II diabetes. Am J Med 1988;84:193–200.
7. Loghmani E, Rickard K, Washburne L, et al. Glycemic response to
sucrose-containing mixed meals in diets of children with insulin-dependent diabetes mellitus.
J Pediatr 1991;119:531–7.
8. American Diabetes Association. Position Statement: nutrition
recommendations and principles for people with diabetes mellitus. Diabetes Care
1999;22:S42–5 [review].
9. Brand-Miller J, Foster-Powell K. Diets with a low glycemic index: from
theory to practice. Nutr Today 1999;34:64–72 [review].
10. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition
principles and recommendations for the treatment and prevention of diabetes and related
complications. Diabetes Care 2002;25:148-98 [review].
11. Lafrance L, Rabasa-Lhoret R, Poisson D, et al. Effects of different
glycaemic index foods and dietary fibre intake on glycaemic control in type 1 patients with
diabetes on intensive insulin therapy. Diabet Med 1998;15:972–8.
12. Giacco R, Parillo M, Rivellese AA, et al. Long-term dietary treatment
with increased amounts of fiber-rich low-glycemic index natural foods improves blood glucose
control and reduces the number of hypoglycemic events in type 1 diabetic patients.
Diabetes Care 2000;23:1461–6.
13. U.S. Department of Agriculture, U.S. Department of Health and Human
Services: Dietary Guidelines for Americans, 2005. Home and Garden Bulletin No. 232, 2005.
Available from URL: www.health.gov/dietaryguidelines/dga2005/document.
14. Vuorinen-Markkola H, Sinisalo M, Koivisto VA. Guar gum in
insulin-dependent diabetes: effects on glycemic control and serum lipoproteins. Am J Clin
Nutr 1992;56:1056–60.
15. Ebeling P, Yki-Jarvinen H, Aro A, et al. Glucose and lipid metabolism
and insulin sensitivity in type 1 diabetes: the effect of guar gum. Am J Clin Nutr
1988;48:98–103.
16. Crane MG, Sample CJ. Regression of diabetic neuropathy with vegan
diet. Am J Clin Nutr 1988;48:926 [abstract #P28].
17. Crane MG, Sample C. Regression of diabetic neuropathy with total
vegetarian (vegan) diet. J Nutr Med 1994;4:431–9.
18. Cohen D, Dodds R, Viberti G. Effect of protein restriction in insulin
dependent diabetics at risk of nephropathy. BMJ 1987;294:795–8.
19. Evanoff G, Thompson C, Bretown J, Weinman E. Prolonged dietary
protein restriction in diabetic nephropathy. Arch Intern Med
1989;149:1129–33.
20. Gin H, Aparicio M, Potauz L, et al. Low-protein, low-phosphorus diet
and tissue insulin sensitivity in insulin-dependent diabetic patients with chronic renal
failure. Nephron 1991;57:411–5.
21. Donaghue KC, Pena MM, Chan AK, et al. Beneficial effects of
increasing monounsaturated fat intake in adolescents with type 1 diabetes. Diabetes Res
Clin Pract 2000;48:193–9.
22. Muntoni S, Cocco P, Aru G, Cucca F. Nutritional factors and worldwide
incidence of childhood type 1 diabetes. Am J Clin Nutr 2000;71:1525–9.
23. Dahl-Jorgensen K, Joner G, Hanssen KF. Relationship between
cows’ milk consumption and incidence of IDDM in childhood. Diabetes Care
1991;14:1081–3.
24. Coleman DL, Kuzava JE, Leiter EH. Effect of diet on incidence of
diabetes in nonobese diabetic mice. Diabetes 1990;39:432–6.
25. Karajalainen J, Martin JM, Knip M, et al. A bovine albumin peptide as
a possible trigger of insulin-dependent diabetes mellitus. N Engl J Med
1992;327:302–7.
26. Gerstein H. Cow’s milk exposure and type I diabetes mellitus.
Diabetes Care 1994;17:13–9.
27. Virtanen SM, Laara E, Hypponen E, et al. Cow’s milk
consumption, HLA–DQB1 genotype, and type I diabetes. Diabetes
2000;49:912–7.
28. Hypponen E, Kenward MG, Virtanen SM, et al. Infant feeding, early
weight gain, and risk of type I diabetes. Diabetes Care 1999;22:1961–5.
29. Verge CF, Howard NJ, Irwig L, et al. Environmental factors in
childhood IDDM. A population-based, case-control study. Diabetes Care
1994;17:1381–9.
30. Bodington MJ, McNallyPG, Burden AC. Cow’s milk and type I
childhood diabetes: no increase in risk. Diabetes Med 1994;11:663–5.
31. Wadsworth EJ, Shield JP, Hunt LP, Baum JD. A case-control study of
environmental factors associated with diabetes in the under 5’s. Diabetes Med
1997;14:390–6.
32. Dahlquist G, Blom L, Lonnberg G. The Swedish Childhood Diabetes
Study—a multivariate analysis of risk determinants for diabetes in different age groups.
Diabetologia 1991;34:757–62.
33. Elliott RB, Harris DP, Hill JP, et al. Type I (insulin-dependent)
diabetes mellitus and cow milk: casein variant consumption. Diabetologia
1999;42:292–6.
34. Scott FWE, Norris JM, Kolb H. Milk and type I diabetes. Diabetes
Care 1996;19:379–83 [review].
35. Atkinson MA, Bowman MA, Kao K-J, et al. Lack of immune responsiveness
to bovine serum albumin in insulin-dependent diabetes. N Engl J Med
1993;329:1853–8.
36. Gerstein H. Cow’s milk exposure and type I diabetes mellitus.
Diabetes Care 1994;17:13–9.
37. Akerblom HK, Knip M. Putative environmental factors in Type 1
diabetes. Diabetes Metab Rev 1998;14:31–67 [review].
38. Hyppönen E, Kenward MG, Virtanen SM, et al. Infant feeding,
early weight gain, and risk of type 1 diabetes. Diabetes Care
1999;22:1961–5.
39. Pettit DJ, Forman MR, Hanson RL, et al. Breast feeding and incidence
of non-insulin-dependent diabetes mellitus in Pima Indians. Lancet
1997;350:166–8.
40. Hyppönen E, Kenward MG, Virtanen SM, et al. Infant feeding,
early weight gain, and risk of type 1 diabetes. Diabetes Care
1999;22:1961–5.
41. Grimm J-J, Muchnick S. Type I diabetes and marathon running.
Diabetes Care 1993;16:1624 [letter].
42. Bell DSH. Exercise for patients with diabetes—benefits, risks,
precautions. Postgrad Med 1992;92:183–96 [review].
43. Ligtenberg PC, Blans M, Hoekstra JB, et al. No effect of long-term
physical activity on the glycemic control in type 1 diabetes patients: a cross-sectional
study. Neth J Med 1999;55:59–63.
44. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition
principles and recommendations for the treatment and prevention of diabetes and related
complications. Diabetes Care 2003;26:S51–S61 [review].
45. Ajani UA, Gaziano JM, Lotufo PA, et al. Alcohol consumption and risk
of coronary heart disease by diabetes status. Circulation 2000;102:500–5.
46. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition
principles and recommendations for the treatment and prevention of diabetes and related
complications. Diabetes Care 2002;25:148–98 [review].
47. Young RJ, McCulloch DK, Prescott RJ, Clarke PF. Alcohol: another risk
factor for diabetic retinopathy? BMJ 1984;288:1035.
48. Moss SE, Klein R, Klein BE. The association of alcohol consumption
with the incidence and progression of diabetic retinopathy. Ophthalmology
1994;101:196–8.
49. Stegmayr B, Lithner F. Tobacco and end stage diabetic nephropathy.
BMJ 1987;295:581–2.
50. Scala C, LaPorte RE, Dorman JS, et al. Insulin-dependent diabetes
mellitus mortality—the risk of cigarette smoking. Circulation
1990;82:37–43.
51. Rimm EB, Manson JE, Stampfer MJ, et al. Cigarette smoking and the
risk of diabetes in women. Am J Public Health 1993;83:211–4.
52. [No authors listed.] Position statement: Tests of glycemia in
diabetes. American Diabetes Association. Diabetes Care 2000;23(Suppl
1):S80–2.
53. Goldstein DE, Little RR, Lorenz RA, et al. Tests of glycemia in
diabetes. Diabetes Care 1995;18:896–909 [review].
54. Gallichan M. Self monitoring of glucose by people with diabetes:
evidence based practice. BMJ 1997;314:964–7 [review].
55. Steel LG. Identifying technique errors. Self-monitoring of blood
glucose in the home setting. J Gerontol Nurs 1994;20:9–12.
56. Foster SA, Goode JV, Small RE. Home blood glucose monitoring. Ann
Pharmacother 1999;33:355–63 [review].
57. Ruhnau KJ, Meissner HP, Finn JR, et al. Effects of 3-week oral
treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic
polyneuropathy. Diabet Med 1999;16:1040–3.
58. Ruhnau KJ, Meissner HP, Finn JR, et al. Effects of 3-week oral
treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic
polyneuropathy. Diabet Med 1999;16:1040–3.
59. Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic
polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter
randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic
Neuropathy. Free Radic Res 1999;31:171–9.
60. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic
diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter
randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in
Diabetic Neuropathy. Diabetes Care 1999;22:1296–301.
61. Morcos M, Borcea V, Isermann B, et al. Effect of alpha-lipoic acid on
the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus:
an exploratory study. Diabetes Res Clin Pract 2001;52:175–83.
62. Anderson RA. Chromium in the prevention and control of diabetes.
Diabetes Metab 2000;26:22–7 [review].
63. Gaby AR, Wright JV. Diabetes. In: Nutritional Therapy in Medical
Practice: Reference Manual and Study Guide. Kent, WA: 1996, 54–64 [review].
64. Lee NA, Reasner CA. Beneficial effect of chromium supplementation on
serum triglyceride levels in NIDDM. Diabetes Care 1994;17:1449–52.
65. Hermann J, Chung H, Arquitt A, et al. Effects of chromium or copper
supplementation on plasma lipids, plasma glucose and serum insulin in adults over age fifty.
J Nutr Elderly 1998;18:27–45.
66. De Leeuw I, Engelen W, Aerts P, Schrans S. Effect of intensive
magnesium supplementation on the in vitro oxidizability of LDL and VLDL in Mg-depleted type 1
diabetic patients. Magnes Res 1998;11:179–82.
67. Sjorgren A, Floren CH, Nilsson A. Oral administration of magnesium
hydroxide to subjects with insulin dependent diabetes mellitus. Magnesium
1988;121:16–20.
68. McNair P, Christiansen C, Madsbad S, et al. Hypomagnesemia, a risk
factor in diabetic retinopathy. Diabetes 1978;27:1075–7.
69. Mimouni F, Miodovnik M, Tsang RC, et al. Decreased maternal serum
magnesium concentration and adverse fetal outcome in insulin-dependent diabetic women.
Obstet Gynecol 1987;70:85–9.
70. American Diabetes Association. Magnesium supplementation in the
treatment of diabetes. Diabetes Care 1992;15:1065–7.
71. Jamal GA, Carmichael H. The effect of gamma-linolenic acid on human
diabetic peripheral neuropathy: a double-blind placebo-controlled trial. Diabet Med
1990;7:319–23.
72. Sima AA, Calvani M, Mehra M, Amato A. Acetyl-L-carnitine improves
pain, nerve regeneration, and vibratory perception in patients with chronic diabetic
neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care
2005;28:89–94.
73. Haugen HN. The blood concentration of thiamine in diabetes. Scand
J Clin Lab Invest 1964;16:260–6.
74. Abbas ZG, Swai ABM. Evaluation of the efficacy of thiamine and
pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy. East African
Med J 1997;74:804–8.
75. Stracke H, Lindemann A, Federlin K. A benfotiamine-vitamin B
combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes
1996;104:311–6.
76. Molnar GD, Berge KG, Rosevear JW, et al. The effect of nicotinic acid
in diabetes mellitus. Metabolism 1964;13:181–9.
77. Gaut ZN, Pocelinko R, Solomon HM, Thomas GB. Oral glucose tolerance,
plasma insulin, and uric acid excretion in man during chronic administration in nicotinic
acid. Metabolism 1971;20:1031–5.
78. Clearly JP. Vitamin B3 in the treatment of diabetes mellitus: case
reports and review of the literature. J Nutr Med 1990;1:217–25.
79. Lewis CM, Canafax DM, Sprafka JM, Bazrbosa JJ. Double-blind
randomized trail of nicotinamide on early-onset diabetes. Diabetes Care
1992;15:121–3.
80. Chase HP, Butler-Simon N, Garg S, et al. A trial of nicotinamide in
newly diagnosed patients with type 1 (insulin-dependent) diabetes mellitus.
Diabetologia 1990;33:444–6.
81. Mendola G, Casamitjana R, Gomis R. Effect of nicotinamide therapy
upon B-cell function in newly diagnosed type 1 (insulin-dependent) diabetic patients.
Diabetologia 1989;32:160–2.
82. Pozzilli P, Browne PD, Kolb H. Meta-analysis of nicotinamide
treatment in patients with recent-onset type 1. The nicotinamide trialists. Diabetes
Care 1996;19:1357–63.
83. Vidal J, Fernandez-Balsells M, Sesmilo G, Aguilera E. Effects of
nicotinamide and intravenous insulin therapy in newly diagnosed type 1 diabetes. Diabetes
Care 2000;23:360–4.
84. Elliott RB, Picher CC, Fergusson DM, Stewart AW. A population based
strategy to prevent insulin-dependent diabetes using nicotinamide. J Pediatr Endocrinol
Metab 1996;9:501–9.
85. Lampeter EF, Klinghammer A, Scherbaum WA, et al. The Deutsche
Nicotinamide Intervention Study. An attempt to prevent type 1 diabetes. Diabetes
1998;47:980–4.
86. Visalli N, Cavallo MG, Signore A, et al. A multi-centre randomized
trial of two different doses of nicotinamide in patients with recent-onset type 1 diabetes
(The IMDIAB VI). Diabetes Metab Res Rev 1999;15:181–5.
87. Wilson RG, Davis RE. Serum pyridoxal concentrations in children with
diabetes mellitus. Pathology 1977;9:95–9.
88. Davis RE, Calder JS, Curnow DH. Serum pyridoxal and folate
concentrations in diabetics. Pathology 1976;8:151–6.
89. McCann VJ, Davis RE. Serum pyridoxal concentrations in patients with
diabetic neuropathy. Aust N Z J Med 1978;8:259–61.
90. Passariello N, Fici F, Giugliano D, et al. Effects of pyridoxine
alpha-ketoglutarate on blood glucose and lactate in type I and II diabetics. Int J Clin
Pharmacol Ther Toxicol 1983;21:252–6.
91. Solomon LR, Cohen K. Erythrocyte O2 transport and metabolism and
effects of vitamin B6 therapy in type II diabetes mellitus. Diabetes
1989;38:881–6.
92. Coggeshall JC, Heggers JP, Robson MC, Baker H. Biotin status and
plasma glucose in diabetics. Ann NY Acad Sci 1985;447:389–92.
93. Koutsikos D, Agroyannis B, Tzanatos-Exarchou H. Biotin for diabetic
peripheral neuropathy. Biomed Pharmacother 1990;44:511–4.
94. Yamane K, Usui T, Yamamoto T, et al. Clinical efficacy of intravenous
plus oral mecobalamin in patients with peripheral neuropathy using vibration perception
thresholds as an indicator of improvement. Curr Ther Res 1995;56:656–70
[review].
95. Kuwabara S, Nakazawa R, Azuma N, et al. Intravenous methylcobalamin
treatment for uremic and diabetic neuropathy in chronic hemodialysis patients. Intern
Med 1999;38:472–5.
96. Abdel-Aziz MT, Abdou MS, Soliman K, et al. Effect of carnitine on
blood lipid pattern in diabetic patients. Nutr Rep Int 1984;29:1071–9.
97. Cunningham JJ, Ellis SL, McVeigh KL, et al. Reduced mononuclear
leukocyte ascorbic acid content in adults with insulin-dependent diabetes mellitus consuming
adequate dietary vitamin C. Metabolism 1991;40:146–9.
98. Davie SJ, Gould BJ, Yudkin JS. Effect of vitamin C on glycosylation
of proteins. Diabetes 1992;41:167–73.
99. Will JC, Tyers T. Does diabetes mellitus increase the requirement for
vitamin C? Nutr Rev 1996;54:193–202 [review].
100. McAuliffe AV, Brooks BA, Fisher EJ, et al. Administration of
ascorbic acid and an aldose reductase inhibitor (tolrestat) in diabetes: effect on urinary
albumin excretion. Nephron 1998;80:277–84.
101. Branch DR. High-dose vitamin C supplementation increases plasma
glucose. Diabetes Care 1999;22:1218 [letter].
102. Mayer-Davis E, Bell RA, Reboussin BA, et al. Antioxidant nutrient
intake and diabetic retinopathy. The San Luis Valley Diabetes Study. Ophthalmology
1998;105:2264–70.
103. Labriji-Mestaghanmi H, Billaudel B, Garnier PE, Sutter BCJ. Vitamin
D and pancreatic islet function. I. Time course for changes in insulin secretion and content
during vitamin deprivation and repletion. J Endocrine Invest
1988;11:577–84.
104. Hypponen E, Laara E, Reunanen A, et al. Intake of vitamin D and risk
of type 1 diabetes: a birth-cohort study. Lancet 2001;358:1500–3.
105. Knekt P, Reunanen A, Marniumi J, et al. Low vitamin E status is a
potential risk factor for insulin-dependent diabetes mellitus. J Intern Med
1999;245:99–102.
106. Ross WM, Creighton MO, Stewart-DeHaan PJ, et al. Modelling cortical
cataractogenesis: 3. In vivo effects of vitamin E on cataractogenesis in diabetic rats.
Can J Ophthalmol 1982;17:61.
107. Bursell SE, Schlossman DK, Clermont AC, et al. High-dose vitamin E
supplementation normalizes retinal blood flow and creatinine clearance in patients with type I
diabetes. Diabetes Care 1999;22:1245–51.
108. Ceriello A, Giugliano D, Quatraro A, et al. Vitamin E reduction of
protein glycosylation in diabetes. Diabetes Care 1991;14:68–72.
109. Duntas L, Kemmer TP, Vorberg B, Scherbaum W. Administration of
d-alpha-tocopherol in patients with insulin-dependent diabetes mellitus. Curr Ther
Res 1996;57:682–90.
110. Jain SK, McVie R, Smith T. Vitamin E supplementation restores
glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic
children. Diabetes Care 2000;23:1389–94.
111. Bursell S-E, Schlossman DK, Clermont AC, et al. High-dose vitamin E
supplementation normalizes retinal blood flow and creatineine clearance in patients with type
I diabetes. Diabetes Care 1999;22:1245–51.
112. Fuller CJ, Chandalia M, Garg A, et al. RRR-alpha-tocopheryl acetate
supplementation at pharmacologic doses decreases low-density-lipoprotein oxidative
susceptibility but not protein glycation in patients with diabetes mellitus. Am J Clin
Nutr 1996;63:753–9.
113. Nakamura T, Higashi A, Nishiyama S, et al. Kinetics of zinc status
in children with IDDM. Diabetes Care 1991;14:553–7.
114. Mocchegiani E, Boemi M, Fumelli P, Fabris N. Zinc-dependent low
thymic hormone level in type I diabetes. Diabetes 1989;12:932–7.
115. Rao KVR, Seshiah V, Kumar TV. Effect of zinc sulfate therapy on
control and lipids in type I diabetes. J Assoc Physicians India 1987;35:52
[abstract].
116. Cunningham JJ, Fu A, Mearkle PL, Brown RG. Hyperzincuria in
individuals with insulin-dependent diabetes mellitus: concurrent zinc status and the effect of
high-dose zinc supplementation. Metabolism 1994;43:1558–62.
117. Crary EJ, McCarty MF. Potential clinical applications for high-dose
nutritional antioxidants. Med Hypotheses 1984;13:77–98.
118. Shigeta Y, Izumi K, Abe H. Effect of coenzyme Q7 treatment on blood
sugar and ketone bodies of diabetics. J Vitaminol (Kyoto) 1966;12:293–8.
119. Henriksen JE, Bruun Andersen C, Hother-Nielsen O, et al. Impact of
ubiquinone (coenzyme Q10) treatment on glycaemic control, insulin requirement and well-being
in patients with Type 1 diabetes mellitus. Diabet Med 1999;16:312–8.
120. Zak A, Zeman M, Hrabak P, et al. Changes in the glucose tolerance
and insulin secretion in hypertriglyceridemia: effects of dietary n-3 fatty acids. Nutr
Rep Int 1989;39:235–42.
121. Okuda Y, Mizutani M, Ogawa M, et al. Long-term effects of
eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type
II diabetes mellitus. J Diabetes Complications 1996;10:280–7.
122. Mori TA, Vandongen R, Masarei JR, et al. Comparison of diets
supplemented with fish oil or olive oil on plasma lipoproteins in insulin-dependent diabetics.
Metabolism 1991;40:241–6.
123. Mori TA, Vandongen R, Masarei JR. Fish oil-induced changes in
apolipoproteins in IDDM subjects. Diabetes Care 1990;13:725–32.
124. Doi K. Effect of konjac fibre (glucomannan) on glucose and lipids.
Eur J Clin Nutr 1995;49(3 Suppl):190S–197S [review].
125. Salway JG, Whitehead L, Finnegan JA, et al. Effect of myo-inositol
on peripheral-nerve function in diabetes. Lancet 1978;2:1282–4.
126. Gregersen G, Borsting H, Theil P, Servo C. Myoinositol and function
of peripheral nerves in human diabetics. Acta Neurol Scand 1978;58:241–8.
127. Kosenko LG. Concentration of trace elements in the blood of patients
with diabetes mellitus. Fed Proc Transl (Suppl) 1965;24:237–8.
128. Baly DL, Schneiderman JS, Garcia-Welsh AL. Effect of manganese
deficiency on insulin binding, glucose transport and metabolism in rat adipocytes. J
Nutr 1990;120:1075–9.
129. Rubenstein AH, Levin NW, Elliott GA. Hypoglycaemia induced by
manganese. Nature (London) 1962;194:188–9.
130. Gaby A. Preventing complications of diabetes Townsend
Letter 1985;32:307 [editorial].
131. Boivin M, Zinsmeister AR, Go VL, DiMagno EP. Effect of a purified
amylase inhibitor on carbohydrate metabolism after a mixed meal in healthy humans. Mayo
Clin Proc 1987;62:249–55.
132. Boivin M, Flourie B, Rizza RA, et al. Gastrointestinal and metabolic
effects of amylase inhibition in diabetics. Gastroenterology
1988;94:387–94.
133. Lankisch M, Layer P, Rizza RA, DiMagno EP. Acute postprandial
gastrointestinal and metabolic effects of wheat amylase inhibitor (WAI) in normal, obese, and
diabetic humans. Pancreas 1998;17:176–81.
134. Holt PR, Thea D, Yang MY, Kotler DP. Intestinal and metabolic
responses to an alpha-glucosidase inhibitor in normal volunteers. Metabolism
1988;37:1163–70.
135. Layer P, Rizza RA, Zinsmeister AR, et al. Effect of a purified
amylase inhibitor on carbohydrate tolerance in normal subjects and patients with diabetes
mellitus. Mayo Clin Proc 1986;61:442–7.
136. Franconi F, Bennardini F, Mattana A, et al. Plasma and platelet
taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine
supplementation. Am J Clin Nutr 1995;61:1115–9.
137. Halberstam M, Cohen N, Schlimovich P, et al. Oral vanadyl sulfate
improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects. Diabetes
1996;45:659–66.
138. Boden G, Chen X, Ruiz J, et al. Effects of vanadyl sulfate on
carbohydrate and lipid metabolism in patients with non-insulin dependent diabetes mellitus.
Metabolism 1996;45:1130–5.
139. Goldfine AB, Patti ME, Zuberi L, et al. Metabolic effects of vanadyl
sulfate in humans with non-insulin-dependent diabetes mellitus: in vivo and in vitro studies.
Metabolism 2000;49:400–10.
140. Aharon Y, Mevorach M, Shamoon H. Vanadyl sulfate does not enhance
insulin action in patients with type 1 diabetes. Diabetes Care 1998;21:2194
[letter].
141. [No authors listed.] Treatment of painful diabetic neuropathy with
topical capsaicin. A multicenter, double-blind, vehicle-controlled study. The Capsaicin Study
Group. Arch Intern Med 1991;151:2225–9.
142. [No authors listed.] Effect of treatment with capsaicin on daily
activities of patients with painful diabetic neuropathy. Capsaicin Study Group. Diabetes
Care 1992;15:159–65.
143. Scharrer A, Ober M. Anthocyanoside in der Behandlung von
Retinopathien. Klin Monatsblatt Augenheilk 1981;178:386–9.
144. [No authors listed]Gymnema sylvestre. Altern Med
Rev 1999;4:46–7.
145. Shanmugasundaram ERB, Rajeswari G, Baskaran K, et al. Use of Gymnema
sylvestre leaf extract in the control of blood glucose insulin-dependent diabetes mellitus.
J Ethnopharmacol 1990;30:281–94.
146. Joffe DJ, Freed SH. Effect of extended release gymnema sylvestre
leaf extract (Beta Fast GXR) alone or in combination with oral hypoglycemics or insulin
regimens for type 1 and type 2 diabetes. Diabetes In: Control Newsletter 2001;76:no
page number.
147. Jain RC, Sachdev KN. A note on hypoglycemic action of onion in
diabetes. Curr Med Pract 1971;15:901–2.
148. Mathew PT, Augusti KT. Hypoglycaemic effect of onion, Allium
cepa Linn, on diabetes mellitus, a preliminary report. Ind J Physiol Pharmacol
1975;19:231–7.
149. Tjokroprawiro A, Pikir BS, Budhiarta AA, et al. Metabolic effects of
onion and green beans on diabetic patients. Tohoku J Exp Med
1983;141(suppl):671–6.
150. Sharma KK, Gupta RK, Gupta S, Samuel KC. Antihyperglycemic effect of
onion: Effect on fasting blood sugar and induced hyperglycemia in man. Ind J Med Res
1977;65:422–9.
151. Maxwell SR, et al. Poor glycaemic control is associated with reduced
serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes
mellitus. Ann Clin Biochem 1997;34( Pt 6):638–44.
152. Jayaprakasam B, Vareed SK, Olson LK, Nair MG. Insulin secretion by
anthocyanins and anthocyanidins. J Agric Food Chem 2005;53:28–31.
153. Zhang T, Hoshino M, Iguchi K, et al. Ginseng root: Evidence for
numerous regulatory peptides and insulinotropic activity. Biomed Res
1990;11:49–54.
154. Suzuki Y, Hikino H. Mechanisms of hypoglycemic activity of panaxans
A and B, glycans of Panax ginseng roots: Effects on plasma levels, secretion, sensitivity and
binding of insulin in mice. Phytother Res 1989;3:20–4.
155. Waki I, Kyo H, Yasuda M, Kimura M. Effects of a hypoglycemic
component of ginseng radix on insulin biosynthesis in normal and diabetic animals. J Pharm
Dyn 1982;5:547–54.125.
156. Hannan JM, Rokeya B, Faruque O, et al. Effect of soluble dietary
fibre fraction of Trigonella foenum graecum on glycemic, insulinemic, lipidemic and platelet
aggregation status of Type 2 diabetic model rats. J Ethnopharmacol
2003;88:73–7.
157. Broca C, Manteghetti M, Gross R, et al. 4-Hydroxyisoleucine: effects
of synthetic and natural analogues on insulin secretion. Eur J Pharmacol
2000;390:339–45.
158. Puri D, Prabhu KM, Murthy PS. Mechanism of action of a hypoglycemic
principle isolated from fenugreek seeds. Indian J Physiol Pharmacol
2002;46:457–62.
159. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood
glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990;44:301–6.
160. Koltringer P, Langsteger W, Lind P, et al. [Ginkgo biloba extract
and folic acid in the therapy of changes caused by autonomic neuropathy]. Acta Med
Austriaca 1989;16:35–7 [in German].
161. Alam MM, Siddiqui MB, Hussain W. Treatment of diabetes through
herbal drugs in rural India. Fitoterapia 1990;61:240–2.
162. Sachdewa A, Khemani LD. Effect of Hibiscus rosa sinensis Linn
ethanol flower extract on blood glucose and lipid profile in streptozotocin induced diabetes
in rats. J Ethnopharmacol 2003;89:61–6.
163. Gray AM, Flatt PR. Insulin-secreting activity of the traditional
antidiabetic plant Viscum album (mistletoe). J Endocrinol 1999;160:409–14.
164. Swanson-Flatt SK, Day C, Bailey CJ, Flatt PR. Evaluation of
traditional plant treatments for diabetes: Studies in streptozotocin-diabetic mice. Acta
Diabetologica Latina 1989;26:51–5.
165. Peirce A. Practical Guide to Natural Medicines. New York:
William Morrow and Co., 1999, 469–71.
166. Van der Hem LG, van der Vliet JA, Bocken CF, et al. Ling Zhi-8:
studies of a new immunomodulating agent. Transplantation 1995;60:438–43.
167. Jones K. Reishi mushroom: Ancient medicine in modern times. Alt
Compl Ther 1998;4:256–66 [review].
168. Abuaisha BB, Costanzi JB, Boulton AJ. Acupuncture for the treatment
of chronic painful peripheral diabetic neuropathy: a long-term study. Diabetes Res Clin
Pract 1998;39:115–21.
169. Zheg HT, Huang XM, Sun JH. Treatment of diabetic cystopathy by
acupuncture and moxibustion. J Tradit Chin Med 1986;6:243–8.
170. Zhang W. Acupuncture for treatment of diabetic urinary bladder
neural dysfunction—a report of 36 cases. J Tradit Chin Med
1997;17:211–3.