Table 2.
Summary table containing number of studies in each study grade category (Meta-analyses = Grade 1, RCT = Grade 2, Single Arm or Cross-over = Grade, narrative review or Case Study = Grade 4), support for diabetes benefit and overall description by supplement ingredient.
| Nutrient | Total studies | Meta-analyses | RCT | Single Arm or cross-over | Narrative review or case study | Do results support the use of this supplement for diabetes management? (Yes, No, Mixed) | Brief summary | |
|---|---|---|---|---|---|---|---|---|
| Human | Animal | |||||||
| Water-soluble vitamins | ||||||||
| Niacin | 3 | 1 | – | 2 | – | – | Yes (1); No (2) | Meta-analysis of human RCTs concluded that niacin supplementation resulted in increased onset of T2DM cases; animal studies examined outcomes of oxidative stress, glucose tolerance, and insulin sensitivity, with mixed results. |
| Vitamin B6 | 4 | – | – | 3 | – | 1 | Yes (2); No (1); Mixed (1) | Supplementation may improve diabetic neuropathy, fasting glucose, and diabetes-related endothelial dysfunction in mice. Narrative review of human studies concluded no benefit. |
| Biotin | 4 | – | – | 1 | – | 3 | Yes (2); No (1); Mixed (1) | In animals, biotin was only effective when combined with exercise. Narrative review of human trials concluded that high-dose biotin may improve fasting glucose and glucokinase function. |
| Folate/Folic Acid | 6 | 3 | 2 | – | 1 | – | Yes (2); No (1); Mixed (3) | Meta-analyses concluded conflicting findings on folic acid supplementation for fasting glucose and HOMA-IR. Supplementation did not result in improvements in HbA1c or homocysteine, but did improve carotid intima media thickness in adults with MetS and decreased risk of stroke in adults with T2DM when co-administered with ACE inhibitor. |
| Vitamin B12 | 5 | – | 1 | – | – | 4 | Yes (2); No (3) | B12 supplementation may be important in individuals on Metformin, as this drug reduces serum levels of the vitamin. Experimental evidence does not support B12 supplementation for diabetes-related outcomes. |
| Vitamin C | 15 | 5 | 4 | 5 | – | 1 | Yes (6); No (3); Mixed (6) | Meta-analyses concluded that supplementation may improve fasting glucose and diastolic blood pressure, but not HbA1c, in adults with T2DM. Human clinical trials conclude no benefit of supplementation on fasting glucose, blood lipids, or onset of T2DM, but may improve anxiety symptoms. Findings from animal models indicate improvements in antioxidant capacity and T lymphocyte function. |
| Fat-soluble vitamins | ||||||||
| Vitamin E | 22 | 5 | 8 | 6 | 1 | 1 | Yes (12); No (8); Mixed (2) | Meta-analyses found no effect on markers of glucose or insulin dynamics with the exception of one displaying improved HbA1C in subjects with uncontrolled glycemia at baseline and low baseline Vitamin E levels. Improvements from human clinical trials indicated mixed findings. A meta-analysis of animal trials displayed significant improvements in wound healing. |
| Minerals | ||||||||
| Chromium | 37 | 6 | 7 | 21 | – | 3 | Yes (17); No (8); Mixed (12) | Meta-analyses display mixed results on glucose control, HbA1C, and TG concentrations. Human and animal trials found mixed results on HbA1C, insulin, and oxidative stress. One meta-analysis found that chromium deficiency was associated with impaired glucose tolerance. |
| Potassium | 1 | – | 1 | – | – | – | Yes (1); No (0) | Single trial in humans concluded improvements in fasting glucose, but not OGTT following supplementation, despite weight gain. weight gain |
| Selenium | 25 | 2 | 10 | 7 | 2 | 4 | Yes (15); No (5); Mixed (5) | No improvement in risk of diabetes in meta-analyses. Human clinical trials suggest improvements in glucose, insulin, insulin resistance, blood lipids, and inflammation. Animal trials display improvements in anti-oxidant enzyme activity, blood glucose, and insulin sensitivity. |
| Sodium | 7 | – | 1 | 5 | 3 | – | Yes (5); No (0); Mixed (2) | In one human trial, GLP-1 was improved but no other measurements related to diabetes. Animal trials display improvements in glucose control, insulin measurements, and body weight. |
| Zinc | 36 | 4 | 6 | 14 | 1 | 10 | Yes (30); No (4); Mixed (2) | Meta-analyses concluded improvements in fasting glucose, HbA1c, fasting insulin, and markers of diabetic kidney injury. Human RCTs found mixed, but mostly positive, effects of supplementation on reducted progression to diabetes in pre-diabetes, improvements in fasting glucose, OGTT, insulin resistance, and blood lipids. Animal trials suggest zinc’s potential to augment metformin treatment, other positive effects on glucose control, insulin, and oxidative stress. |
| Amino acids | ||||||||
| Beta-Alanine | 1 | – | – | – | – | 1 | Yes (1); No (0) | May indirectly improve T2DM complications through increases in intramuscular carnosine concentrations. |
| Taurine | 17 | – | – | 12 | 3 | 2 | Yes (9); No (3); Mixed (6) | Human crossover trials found no effect on insulin sensitivity or platelet aggregation. Animal work indicates potential benefit for complications including diabetic retinopathy and endothelial dysfunction, but mixed results for fasting glucose, beta cell function, and glucose tolerance. Narrative reviews cite the potential of taurine yet the lack of clinical trials. |
| l-Leucine | 18 | – | 1 | 11 | – | 6 | Yes (11); No (4); Mixed (3) | Only human RCT found no benefit on improvements in HbA1C or insulin sensitivity. Animal studies evidenced improvements in fasting glucose and OGTT, but mixed effects on insulin resistance. Supplementation did not improve pancreatic insulin output. Narrative reviews concluded mixed results on glucose homeostasis. |
| Other | ||||||||
| Caffeine | 3 | – | 1 | 1 | – | 1 | Yes (0); No (2); Mixed (1) | Human RCT in T1DM patients concluded caffeine may attenuate post-exercise drop in glycemia, but also may result in late-onset hypoglycemia. Animal study showed no benefit on platelet aggregation or ATP signaling. |
| Dietary fiber | 26 | 1 | 6 | 10 | 1 | 8 | Yes (18); No (2); Mixed (6) | Many different fiber sources were tested. Meta-analysis results show improvements in HbA1C, HOMA-IR, and insulin levels following soluble fiber supplementation. Human RCTs demonstrated benefits of soluble fiber on postprandial and fasting glucose, but not intravenous glucose tolerance. Animal RCTs examined various soluble fibers and prebiotics and demonstrated benefits in body weight, hyperglycemia, hyperinsulinemia, and microbial diversity. Several narrative reviews on prebiotics suggest their benefit for microbial diversity, and improvements in glucose and insulin concentrations. |
| Protein | 4 | – | 1 | 1 | – | 1 | Yes (2); No (1); Mixed (1) | Human RCT results in mixed effects on adipokine profiles. Animal trials suggest benefits for insulin sensitivity following beta-conglycinin supplementation; but glucosamine supplementation induced insulin resistance. A narrative review suggests milk proteins may improve postprandial glucose. |
| Trans fat | 6 | – | 1 | 4 | 1 | 1 | Yes (2); No (1); Mixed (2) | CLA supplementation impaired insulin sensitivity in men with obesity, but improved insulin secretion in animal studies, despite other mixed results. Trans-vaccenic acid improved insulin sensitivity in rats. |
| Totals | 240 | 27 | 50 | 103 | 13 | 47 | ||
ACE angiotensin converting enzyme, ATP adenosine triphosphate, CLA conjugated linoleic acid, GLP-1 glucagon-like peptide 1, HbA1C hemoglobin A1C, HOMA-IR homeostatic model of insulin resistance, MetS Metabolic Syndrome, OGTT oral glucose tolerance test, RCT randomized control trial, T1DM type 1 diabetes mellitus, T2DM type 2 diabetes mellitus, TG triglycerides.