Type 2 Diabetes

Chromium status appears to be an important factor in glucose metabolism: individuals with lower chromium levels are more likely to have type 2 diabetes or pre-diabetes than those with higher levels, and low chromium status is associated with poor glycemic control and insulin resistance in people with type 2 diabetes.^24,25,26,27 Furthermore, chromium supplementation has been shown to improve glucose control, insulin sensitivity, and other metabolic variables in people with insulin resistance and type 2 diabetes.

In one placebo-controlled trial that included 64 participants with type 2 diabetes and heart disease, taking 200 mcg per day of chromium was associated with greater weight loss, lower fasting glucose and insulin levels, improved insulin sensitivity, and reduced blood pressure after four months. In addition, chromium supplementation led to lower levels of inflammatory markers and higher antioxidant capacity.²⁸ A meta-analysis of 28 other randomized controlled trials concluded that chromium supplementation, particularly chromium chloride or chromium picolinate, reduces fasting blood glucose levels, triglyceride levels, and hemoglobin A1c values, and increases HDL-cholesterol levels.²⁹ Because of its ability to help regulate dopamine and serotonin activity, some researchers propose chromium may be especially beneficial in people with type 2 diabetes who also suffer from depression or binge eating.³⁰

Studies showing beneficial effects from chromium supplementation have generally used 200 mcg per day or more. Many doctors recommend up to 1,000 mcg per day for people with diabetes.

Folic acid, sometimes called vitamin B9, is needed along with vitamins B6 and B12 for healthy homocysteine metabolism. Elevated homocysteine levels have been associated with a range of chronic cardiovascular and neurological diseases.⁴⁶ A meta-analysis pooled findings from 18 randomized controlled trials with a combined total of over 21,000 participants with type 2 diabetes. The analysis found folic acid supplementation lowered fasting blood glucose levels and reduced insulin resistance, but had no discernible effect on HbA1c, a marker of long-term blood glucose control.⁴⁷

Meta-analyses of studies have found high homocysteine levels are correlated with increased risk of diabetic retinopathy (damage to the visual center of the eye) and nephropathy (kidney damage).^48,49 Because folic acid supplementation can lower high homocysteine levels in people with type 2 diabetes, it may be protective.⁵⁰ In a preliminary trial, a B vitamin supplement providing 6 mg of methylfolate (the active form of folic acid), along with 70 mg of pyridoxal 5-phosphate (active vitamin B6) and 4 mg of methylcobalamin (active vitamin B12), per day improved retinal function and reduced retinal edema in participants with type 2 diabetes-related retinopathy.⁵¹ Several preliminary and placebo-controlled trials using the same B vitamin supplement indicate this combination may reduce symptoms of neuropathy related to type 2 diabetes.^52,53,54

Numerous studies have shown that poor magnesium status is associated with insulin resistance and type 2 diabetes.^59,60,61,62 Furthermore, diabetes itself causes increased magnesium loss, resulting in a vicious cycle of dropping magnesium levels and worsening insulin resistance.^63,64 Low magnesium levels have also been correlated with poor blood glucose control and increased risk of complications such as heart disease, kidney disease, and nerve damage in those with type 2 diabetes.^{65,66,67,68,69} Moreover, meta-analyses of randomized controlled trials have concluded that magnesium supplementation can lower blood pressure and decrease the risk of diabetes-related cardiovascular disease in people with type 2 diabetes.^70,71

Taking 250 mg of elemental magnesium (from magnesium oxide, gluconate, and lactate) per day for three months improved glycemic control and insulin sensitivity in a randomized controlled trial with 42 participants with type 2 diabetes.⁷² In a placebo-controlled trial, patients with diabetes-related kidney failure taking 250 mg of elemental magnesium (from magnesium oxide) per day for 24 weeks had improved vascular health, as well as reduced insulin, total cholesterol, LDL-cholesterol, and C-reactive protein levels, Hgb1c values, and insulin resistance scores, and increased antioxidant capacity.⁷³ However, another placebo-controlled trial that included people with type 2 diabetes and related kidney disease found the combination of 250 mg magnesium (from magnesium oxide) plus 47 mg calcium (from calcium carbonate) per day improved lipid profiles but had no effect on glucose control and worsened insulin resistance after 12 weeks.⁷⁴ Many doctors recommend that people with diabetes supplement with 200 to 600 mg per day of elemental magnesium from a highly bioavailable magnesium salt without added calcium.

Biotin is a B vitamin needed to activate a major enzyme involved in glucose metabolism. In a clinical trial, 43 participants with type 2 diabetes were found to have lower serum biotin levels compared to healthy people without diabetes. Supplementation with 3 mg of biotin three times per day (along with a probiotic) for two months led to normalization of glucose levels. In addition, five participants who continued to take biotin for four years maintained these benefits.¹⁰⁹ In another trial, taking 64.1 micromoles (15 mg) of biotin per day for 28 days led to reductions in high triglyceride levels, but had no effect on glucose or insulin levels in people with type 2 diabetes.¹¹⁰ Case reports suggest long-term treatment with high-dose biotin may reduce symptoms of diabetes-related nerve pain.¹¹¹

It is thought that biotin may have a synergistic effect with chromium. Placebo-controlled trials investigating the effects of taking 600 micrograms of chromium (as chromium picolinate) plus 2 mg of biotin per day have found this combination improves blood glucose control and triglyceride and other lipid levels; however, it is worth noting these trials were funded by the manufacturer of the chromium/biotin supplement they used.^{112,113,114,115}

Preliminary research has suggested that pycnogenol may help lower blood glucose levels in people with type 2 diabetes.¹⁸⁷ In a placebo-controlled trial with 48 subjects with type 2 diabetes, 125 mg of pycnogenol per day for 12 weeks led to reductions in fasting blood glucose and LDL-cholesterol levels, as well as blood pressure and HbA1c.¹⁸⁸ In another 12-week placebo-controlled trial with 77 subjects with type 2 diabetes, 100 mg per day of pycnogenol lowered blood glucose levels, but improvement in HbA1c was not statistically significant.¹⁸⁹

Pycnogenol has been shown to be helpful for improving small vessel health and restoring healthy blood flow in people with type 2 diabetes and related vascular symptoms.¹⁹⁰ Clinical trials have also reported its benefits in treating microvascular complications of type 2 diabetes, such as diabetic retinopathy, skin ulcers, and neuropathy. The doses of pycnogenol used in these studies are 100 to 200 mg per day.^{191,192,193,194,195}

Vitamin C, at a dose of 500 mg twice per day, was found to reduce fasting blood glucose levels, although not HbA1c, after four months in a placebo-controlled trial.²⁰⁶ A meta-analysis of other controlled trials found vitamin C supplementation can reduce blood glucose levels (but not HbA1c) in people with type 2 diabetes, and is especially effective in those who are older and those who have taken vitamin C for 30 days or more.²⁰⁷

Through its anti-inflammatory and antioxidant effects, vitamin C has been shown to lower blood pressure and improve cardiovascular health in people with type 2 diabetes.²⁰⁸ In addition, like other antioxidants, vitamin C reduces formation of advanced glycation end-products (AGEs), which cause widespread damage to proteins and DNA.²⁰⁹ Antioxidants like vitamins C and E protect against damage to micro-vessels and therefore have the potential to help prevent type 2 diabetes complications such as retinopathy, nephropathy, and neuropathy.^210,211 Furthermore, low vitamin C levels in blood and in the eye have been correlated with increased risk of retinopathy.^212,213 In a pilot study, a combination supplement with vitamin C and other antioxidant vitamins, minerals, and plant extracts improved vision in subjects with type 2 diabetes and early stage retinopathy.²¹⁴

High-dose vitamin C supplementation has been reported to interfere with some devices for self-monitoring of blood glucose levels. This can raise the risk of overtreatment leading to hypoglycemia.²¹⁵ Therefore it is important that people with type 2 diabetes who rely on self-monitoring glucose devices talk with their healthcare provider before starting a vitamin C supplement.

Vitamin D is now recognized as necessary for healthy immune function, regulation of inflammatory processes, insulin production, and cellular responsiveness to insulin.^216,217 Vitamin D deficiency has been linked to high blood glucose levels, insulin resistance, type 2 diabetes, and diabetes complications.^218,219 Numerous studies have examined the effect of vitamin D supplementation on blood glucose control in people with type 2 diabetes, and meta-analyses of randomized controlled trials have found evidence of benefits, particularly in those with vitamin D deficiency.^220,221,222 One meta-analysis found a minimum dose of 4,000 IU of vitamin D per day is needed to improve blood glucose management and insulin sensitivity in people with type 2 diabetes.²²³

Vitamin D is vital for both large and small blood vessel health, and deficiency has been associated with cardiovascular and microvascular diabetes complications. More research is needed to clearly establish a role for vitamin D supplementation in prevention and treatment of diabetes complications.²²⁴

Zinc is important for normal pancreatic insulin production and release. Zinc deficiency is very common in people with type 2 diabetes and may be related to genetic susceptibility.²²⁵ In one study, zinc deficiency was present in 77% of subjects being treated with metformin (a widely used anti-diabetes drug) and 90% of subjects being treated with both metformin and glimepiride (another anti-diabetes drug).²²⁶ A growing body of evidence shows zinc supplementation may be helpful in preventing and treating type 2 diabetes, but only those with poor zinc status appear to benefit.²²⁷

In a placebo-controlled trial that included 200 participants with prediabetes, average zinc levels were noted to be lower than normal and taking 20 mg of zinc per day for one year resulted in reduced blood glucose, cholesterol, and LDL-cholesterol levels, and improved the fasting response to glucose ingestion (glucose tolerance), measures of insulin resistance, and pancreatic cell function. Moreover, 25% of those in given placebo progressed to type 2 diabetes, while only 11% of those given zinc developed diabetes.²²⁸ Nevertheless, the relationship between zinc status and type 2 diabetes risk remains unclear, as some research has noted a correlation between higher blood zinc levels and increased diabetes risk.²²⁹

A controlled trial in people with type 2 diabetes with urinary protein loss (a sign of diabetes-related kidney damage) found that adding 50 mg of zinc (as zinc sulphate) to their diabetes treatment for 12 weeks improved blood glucose and triglyceride levels and reduced urinary protein loss.²³⁰ Studies have also shown that supplementing with a combination of melatonin (10 mg per day) plus zinc (50 mg per day [as zinc acetate]), can improve blood glucose and lipid levels and reduce urinary protein loss in people with type 2 diabetes.^231,232

Many doctors recommend that people with type 2 diabetes and low zinc levels supplement with 15 to 25 mg of zinc per day to normalize zinc levels. Taking high doses of supplemental zinc long term increases the risk of copper deficiency. Most multivitamin-mineral supplements provide adequate copper to prevent deficiency.