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No, there is no high-quality evidence that supports using complementary or alternative agents to lower hemoglobin A1c (HbA1c) in patients with noninsulin-dependent type 2 diabetes. Oral chromium in widely varying doses reduces HbA1c a small amount (strength of recommendation [SOR]: C, meta-analysis of low-quality randomized, controlled trials [RCTs] of disease-oriented outcomes, with inconsistent results).
Oral cinnamon 1 to 3 g/d causes a small (<0.1%) drop in HbA1c (SOR: C, meta-analysis of low-quality RCTs of disease-oriented outcomes).
Fenugreek, milk thistle, safflower oil, and sweet potato extract may also reduce HbA1c (SOR: C, small, low-quality RCTs of disease-oriented outcomes).
EVIDENCE SUMMARY
Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).1-8
Meta-analyses evaluate effects of chromium and cinnamon
A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.1 Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.
A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.2 After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).
When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.
What about caiapo, fenugreek, milk thistle, and safflower oil?
Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.3,4
TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes
CAA* | Dose/day | Concurrent diabetes therapy | Study type | Study size | Study duration | Difference in HbA1c (in HbA1c units) | 95% CI or P value |
Chromium1 | 1.28-1000 mcg | Not given | Meta-analysis of 13 RCTs | 381 | 3 wk-8 mo | -0.6† | -0.9 to -0.2 |
Cinnamon2 | 1-3 g | Various oral hypoglycemic agents‡ | Meta-analysis of 5 RCTs | 315 | 1.5-4 mo | -0.09 (WMD)† | -0.14 to -0.04 |
Caiapo3 | 4 g | Diet only | RCT | 61 | 5 mo | -0.21 (caiapo)§ +0.25 (placebo)§ | P=.08
P=.0001 |
Caiapo4 | 4 g | Diet only | RCT | 61 | 3 mo | -0.53 (caiapo)§ +0.06 (placebo)§ | P<.001
P=.23 |
Trigonella foenum-graecum (fenugreek)5 | 6.84 g | Sulfonylurea | RCT | 69 | 3 mo | -1.46 (fenugreek)§ -0.41 (placebo)§ | P<.05
P<.05 |
Silybum marianum (milk thistle)6 | 200 mg | Metformin and sulfonylurea | RCT | 51 | 4 mo | -1.0 (milk thistle)§ +1.2 (placebo)§ | P<.001
P<.0001 |
Silybum marianum (milk thistle)7 | 200 mg | Sulfonylurea | RCT | 38 | 4 mo | -1.5 (milk thistle)§ -0.5 (placebo)§ | P<.05
P=NS |
Safflower oil vs conjugated linoleic acid8 | 8 g | Various oral hypoglycemic agents‡ | DBRCD | 35 | 4 mo | -0.6 (safflower oil)§ +0.1 (conjugated linoleic acid)§ | P=.0007
P=NS |
CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.
Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.5-8
RECOMMENDATIONS
Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.9
1. Balk ME, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007;30:2154-2163.
2. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: Systematic review and meta analysis. Clin Nutr. 2012;31:609-615.
3. Ludvik B, Hanefeld M, Pacini G. Improved metabolic control by Ipomoea batatas (Caiapo) is associated with increased adiponectin and decreased fibrinogen levels in type 2 diabetic subjects. Diabetes Obes Metab. 2008;10:586-592.
4. Ludvik, B, Neuffer, B, Pacini G. Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic subjects treated with diet. Diabetes Care. 2004;27:436-440.
5. Lu FR, Shen L, Qin Y, et al. Clinical observation on trigonella foenum-graecum L. total saponins in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Chin J Integr Med. 2008;14:56-60.
6. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybummarianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2006;20:1036-1039.
7. Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food. 2007;10:543-547.
8. Asp ML, Collene AL, Norris LE, et al. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized,double-masked, crossover study. Clin Nutr. 2011;30:443-449.
9. American Diabetes Association; Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2008;31 suppl 1:S61-S78.
10. Diabetes UK Nutrition Working Group, Dyson PA, Kelly T, Deakin T, et al. Evidence-Based Nutrition Guidelines for the Prevention and Management of Diabetes. Diabetes UK Web site. Available at: www.diabetes.org.uk/Documents/Reports/nutritional-guidelines-2013-amendment-0413.pdf. Accessed October 2, 2013.
No, there is no high-quality evidence that supports using complementary or alternative agents to lower hemoglobin A1c (HbA1c) in patients with noninsulin-dependent type 2 diabetes. Oral chromium in widely varying doses reduces HbA1c a small amount (strength of recommendation [SOR]: C, meta-analysis of low-quality randomized, controlled trials [RCTs] of disease-oriented outcomes, with inconsistent results).
Oral cinnamon 1 to 3 g/d causes a small (<0.1%) drop in HbA1c (SOR: C, meta-analysis of low-quality RCTs of disease-oriented outcomes).
Fenugreek, milk thistle, safflower oil, and sweet potato extract may also reduce HbA1c (SOR: C, small, low-quality RCTs of disease-oriented outcomes).
EVIDENCE SUMMARY
Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).1-8
Meta-analyses evaluate effects of chromium and cinnamon
A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.1 Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.
A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.2 After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).
When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.
What about caiapo, fenugreek, milk thistle, and safflower oil?
Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.3,4
TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes
CAA* | Dose/day | Concurrent diabetes therapy | Study type | Study size | Study duration | Difference in HbA1c (in HbA1c units) | 95% CI or P value |
Chromium1 | 1.28-1000 mcg | Not given | Meta-analysis of 13 RCTs | 381 | 3 wk-8 mo | -0.6† | -0.9 to -0.2 |
Cinnamon2 | 1-3 g | Various oral hypoglycemic agents‡ | Meta-analysis of 5 RCTs | 315 | 1.5-4 mo | -0.09 (WMD)† | -0.14 to -0.04 |
Caiapo3 | 4 g | Diet only | RCT | 61 | 5 mo | -0.21 (caiapo)§ +0.25 (placebo)§ | P=.08
P=.0001 |
Caiapo4 | 4 g | Diet only | RCT | 61 | 3 mo | -0.53 (caiapo)§ +0.06 (placebo)§ | P<.001
P=.23 |
Trigonella foenum-graecum (fenugreek)5 | 6.84 g | Sulfonylurea | RCT | 69 | 3 mo | -1.46 (fenugreek)§ -0.41 (placebo)§ | P<.05
P<.05 |
Silybum marianum (milk thistle)6 | 200 mg | Metformin and sulfonylurea | RCT | 51 | 4 mo | -1.0 (milk thistle)§ +1.2 (placebo)§ | P<.001
P<.0001 |
Silybum marianum (milk thistle)7 | 200 mg | Sulfonylurea | RCT | 38 | 4 mo | -1.5 (milk thistle)§ -0.5 (placebo)§ | P<.05
P=NS |
Safflower oil vs conjugated linoleic acid8 | 8 g | Various oral hypoglycemic agents‡ | DBRCD | 35 | 4 mo | -0.6 (safflower oil)§ +0.1 (conjugated linoleic acid)§ | P=.0007
P=NS |
CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.
Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.5-8
RECOMMENDATIONS
Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.9
No, there is no high-quality evidence that supports using complementary or alternative agents to lower hemoglobin A1c (HbA1c) in patients with noninsulin-dependent type 2 diabetes. Oral chromium in widely varying doses reduces HbA1c a small amount (strength of recommendation [SOR]: C, meta-analysis of low-quality randomized, controlled trials [RCTs] of disease-oriented outcomes, with inconsistent results).
Oral cinnamon 1 to 3 g/d causes a small (<0.1%) drop in HbA1c (SOR: C, meta-analysis of low-quality RCTs of disease-oriented outcomes).
Fenugreek, milk thistle, safflower oil, and sweet potato extract may also reduce HbA1c (SOR: C, small, low-quality RCTs of disease-oriented outcomes).
EVIDENCE SUMMARY
Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).1-8
Meta-analyses evaluate effects of chromium and cinnamon
A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.1 Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.
A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.2 After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).
When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.
What about caiapo, fenugreek, milk thistle, and safflower oil?
Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.3,4
TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes
CAA* | Dose/day | Concurrent diabetes therapy | Study type | Study size | Study duration | Difference in HbA1c (in HbA1c units) | 95% CI or P value |
Chromium1 | 1.28-1000 mcg | Not given | Meta-analysis of 13 RCTs | 381 | 3 wk-8 mo | -0.6† | -0.9 to -0.2 |
Cinnamon2 | 1-3 g | Various oral hypoglycemic agents‡ | Meta-analysis of 5 RCTs | 315 | 1.5-4 mo | -0.09 (WMD)† | -0.14 to -0.04 |
Caiapo3 | 4 g | Diet only | RCT | 61 | 5 mo | -0.21 (caiapo)§ +0.25 (placebo)§ | P=.08
P=.0001 |
Caiapo4 | 4 g | Diet only | RCT | 61 | 3 mo | -0.53 (caiapo)§ +0.06 (placebo)§ | P<.001
P=.23 |
Trigonella foenum-graecum (fenugreek)5 | 6.84 g | Sulfonylurea | RCT | 69 | 3 mo | -1.46 (fenugreek)§ -0.41 (placebo)§ | P<.05
P<.05 |
Silybum marianum (milk thistle)6 | 200 mg | Metformin and sulfonylurea | RCT | 51 | 4 mo | -1.0 (milk thistle)§ +1.2 (placebo)§ | P<.001
P<.0001 |
Silybum marianum (milk thistle)7 | 200 mg | Sulfonylurea | RCT | 38 | 4 mo | -1.5 (milk thistle)§ -0.5 (placebo)§ | P<.05
P=NS |
Safflower oil vs conjugated linoleic acid8 | 8 g | Various oral hypoglycemic agents‡ | DBRCD | 35 | 4 mo | -0.6 (safflower oil)§ +0.1 (conjugated linoleic acid)§ | P=.0007
P=NS |
CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.
Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.5-8
RECOMMENDATIONS
Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.9
1. Balk ME, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007;30:2154-2163.
2. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: Systematic review and meta analysis. Clin Nutr. 2012;31:609-615.
3. Ludvik B, Hanefeld M, Pacini G. Improved metabolic control by Ipomoea batatas (Caiapo) is associated with increased adiponectin and decreased fibrinogen levels in type 2 diabetic subjects. Diabetes Obes Metab. 2008;10:586-592.
4. Ludvik, B, Neuffer, B, Pacini G. Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic subjects treated with diet. Diabetes Care. 2004;27:436-440.
5. Lu FR, Shen L, Qin Y, et al. Clinical observation on trigonella foenum-graecum L. total saponins in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Chin J Integr Med. 2008;14:56-60.
6. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybummarianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2006;20:1036-1039.
7. Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food. 2007;10:543-547.
8. Asp ML, Collene AL, Norris LE, et al. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized,double-masked, crossover study. Clin Nutr. 2011;30:443-449.
9. American Diabetes Association; Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2008;31 suppl 1:S61-S78.
10. Diabetes UK Nutrition Working Group, Dyson PA, Kelly T, Deakin T, et al. Evidence-Based Nutrition Guidelines for the Prevention and Management of Diabetes. Diabetes UK Web site. Available at: www.diabetes.org.uk/Documents/Reports/nutritional-guidelines-2013-amendment-0413.pdf. Accessed October 2, 2013.
1. Balk ME, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007;30:2154-2163.
2. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: Systematic review and meta analysis. Clin Nutr. 2012;31:609-615.
3. Ludvik B, Hanefeld M, Pacini G. Improved metabolic control by Ipomoea batatas (Caiapo) is associated with increased adiponectin and decreased fibrinogen levels in type 2 diabetic subjects. Diabetes Obes Metab. 2008;10:586-592.
4. Ludvik, B, Neuffer, B, Pacini G. Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic subjects treated with diet. Diabetes Care. 2004;27:436-440.
5. Lu FR, Shen L, Qin Y, et al. Clinical observation on trigonella foenum-graecum L. total saponins in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Chin J Integr Med. 2008;14:56-60.
6. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybummarianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2006;20:1036-1039.
7. Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food. 2007;10:543-547.
8. Asp ML, Collene AL, Norris LE, et al. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized,double-masked, crossover study. Clin Nutr. 2011;30:443-449.
9. American Diabetes Association; Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2008;31 suppl 1:S61-S78.
10. Diabetes UK Nutrition Working Group, Dyson PA, Kelly T, Deakin T, et al. Evidence-Based Nutrition Guidelines for the Prevention and Management of Diabetes. Diabetes UK Web site. Available at: www.diabetes.org.uk/Documents/Reports/nutritional-guidelines-2013-amendment-0413.pdf. Accessed October 2, 2013.
Evidence-based answers from the Family Physicians Inquiries Network