Type 2 Diabetes (Holistic)

Alpha lipoic acid is a powerful natural antioxidant that protects blood vessels and other tissues from free radical damage. Numerous clinical trials have been conducted to examine its effects in people with type 2 diabetes. The strongest evidence for its beneficial effects comes from trials in subjects with diabetes-related nerve complications (neuropathy). One placebo-controlled trial monitored 460 participants with type 1 or type 2 diabetes and mild to moderate polyneuropathy taking 600 mg per day of alpha lipoic acid or placebo for four years. Those taking alpha lipoic acid had significantly reduced symptoms and progression of neuropathy. In addition, clinical research suggests that alpha lipoic acid may improve insulin sensitivity, blood glucose control, and lipid metabolism, support weight loss, and reduce the impacts of diabetic complications such as retinopathy (damage to the retina in the eye), nephropathy (kidney dysfunction), and erectile dysfunction. Studies reporting benefits have generally used doses ranging from 600 to 1,200 mg of alpha lipoic acid per day.

The first report on the blood glucose-lowering effects of brewer’s yeast emerged in 1958. Brewer’s yeast is a source of dietary chromium and low chromium levels have been associated with higher blood glucose, insulin, and inflammatory marker levels, as well as higher blood pressure and greater insulin resistance in people with type 2 diabetes. Preliminary and placebo-controlled research has indicated brewer’s yeast, in doses from 1.8–9 grams (providing up to 42 micrograms of chromium) per day may reduce blood glucose, triglyceride, and LDL-cholesterol levels, and increase HDL-cholesterol levels. One study compared brewer’s yeast providing 23.3 mcg of chromium per day to 200 mcg of chromium chloride per day in people with type 2 diabetes and found more favorable effects from the yeast, suggesting chromium in yeast may be more bioavailable. Taking chromium-enriched yeast supplements has also been found to improve glucose metabolism in subjects with type 2 diabetes. In a twelve-week trial, eating whole wheat bread made with chromium-enriched yeast was noted to improve glycemic control, body weight, and blood pressure compared to regular whole wheat bread in people with type 2 diabetes.

Double-blind trials have shown that topical application of creams containing 0.025 to 0.075% capsaicin (from cayenne [Capsicum frutescens]) can relieve symptoms of diabetic neuropathy (numbness and tingling in the extremities caused by diabetes). Four or more applications per day may be required to relieve severe pain. This should be done only under a doctor’s supervision.

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. 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. 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. 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.

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.

Fenugreek seeds have a long history of use in the treatment of diabetes, and some fenugreek constituents have demonstrated anti-diabetes actions such as reducing starch digestion and glucose absorption in the gut, improving insulin sensitivity, and increasing insulin secretion. In clinical research, 60 subjects with type 2 diabetes who took 10 grams per day of hot water-soaked fenugreek seeds for six months had better blood glucose control than matched patients who received no fenugreek. Taking 10 grams per day of fenugreek seeds was reported to reduce the risk of type 2 diabetes in people with pre-diabetes in another controlled study. A placebo-controlled trial found 500 mg of fenugreek extract containing high amounts of constituents called furostanolic saponins improved blood glucose control and reduced medication need in people with type 2 diabetes after 90 days. A meta-analysis that included eight randomized controlled trials noted that, despite the overall low quality of the studies, fenugreek, in doses of at least 5 grams per day, appears to improve blood glucose control in people with type 2 diabetes, and the effects are greater with higher doses. Doses of up to 100 grams per day of fenugreek were used in the studies.

Studies have consistently shown that high intake of dietary fiber improves insulin resistance and lowers the risk of type 2 diabetes by 20–30%. This effect is mainly attributable to grain and cereal fibers, rather than fibers from fruits and vegetables, and may be due in large part to their positive impact on the gut microbiome. Meta-analyses of randomized controlled trials in people with type 2 diabetes have found that supplementing with approximately 13–15 grams of soluble fiber per day can improve blood glucose control and reduce insulin resistance. Psyllium, guar gum, oat bran, and inulin are examples of soluble fibers or soluble fiber sources that have been shown to be beneficial in type 2 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. 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.

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). Because folic acid supplementation can lower high homocysteine levels in people with type 2 diabetes, it may be protective. 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. 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.

Glucomannan is a water-soluble dietary fiber derived from konjac root (Amorphophallus konjac) that delays stomach emptying, leading to a more gradual carbohydrate digestion and glucose absorption. Supplementing with glucomannan before eating has been shown reduce the post-meal elevation of blood glucose levels and long-term supplementation is associated with better blood glucose control and improvements in LDL-cholesterol levels in people with type 2 diabetes. Research in animals suggests glucomannan may be helpful in managing diabetes-related kidney dysfunction. Doses between 1 and 10 grams of glucomannan per day have demonstrated efficacy in clinical research.

Numerous studies have shown that poor magnesium status is associated with insulin resistance and type 2 diabetes. Furthermore, diabetes itself causes increased magnesium loss, resulting in a vicious cycle of dropping magnesium levels and worsening insulin resistance. 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. 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.

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. 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. 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. 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.

The gut microbiome is increasingly recognized as a key player in regulating immune and metabolic functions in the body, and a growing body of research suggests probiotics may be beneficial to people with type 2 diabetes. Multiple clinical trials, reviews, and meta-analyses have shown that probiotic supplements can have a positive impact on blood glucose control, cholesterol and triglyceride levels, and blood pressure in people with type 2 diabetes. One review reported the best evidence is for supplements with multiple strains, including Lactobacillus acidophilus,Lactobacillus bulgaricus,Streptococcus thermophilus, and Bifidobacterium lactis, taken in amounts of 7 billion or more colony forming units (CFU) for six to 12 weeks.

Supplementing with psyllium has been shown to be a safe and effective way to improve control of blood glucose and cholesterol. A large review and meta-analysis that included 35 randomized controlled trials found that long-term psyllium use, at a dose of 10.2 grams per day taken before meals, reduces fasting glucose an average of 37 mg/dL and HgbA1c an average of 0.97% in people with type 2 diabetes, with greater improvements seen in those with higher baseline fasting blood glucose levels.

In a double-blind study of people with diabetic 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. 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.

Several randomized controlled trials and two meta-analyses have found that aloe vera can help lower blood glucose levels and HgbA1c, and may improve lipid levels, in people with type 2 diabetes. The variety in study protocols makes it difficult to identify a consistently effective dose. In one trial, taking 300 mg of aloe vera leaf gel twice per day was effective for improving glycemic control and lipid metabolism in people with medically treated type 2 diabetes; in another trial, both 100 and 200 mg per day of powdered aloe vera gel had beneficial effects.

Numerous clinical trials indicate American ginseng (Panax quinquefolius) may improve insulin sensitivity and glucose metabolism. Results from a placebo-controlled crossover study show a beneficial effect of 3 grams of American ginseng extract per day in participants with type 2 diabetes: eight weeks of treatment resulted in reductions in HgbA1c, fasting blood glucose levels, blood pressures, and LDL-cholesterol levels compared to placebo. In a twelve-week placebo-controlled trial that included 64 participants with type 2 diabetes and related high blood pressure, 3 grams of American ginseng per day resulted in decreased blood vessel stiffness and lower blood pressure. A typical dose used in clinical trials and found to be safe in those with type 2 diabetes is 1 gram three times daily. Some American ginseng extracts are standardized for their ginsenoside content.

Asian ginseng is commonly used in Traditional Chinese Medicine to treat diabetes. Asian ginseng extracts and constituents known as ginsenosides have demonstrated antidiabetic effects such as lowering glucose levels, improving insulin levels, reducing insulin resistance scores, and improving lipid levels in multiple clinical trials and laboratory studies. In one placebo-controlled trial, taking 5 grams of Asian ginseng per day for 12 weeks led to better blood glucose response to glucose ingestion in participants with type 2 diabetes. A placebo-controlled trial using various doses of a vinegar extract of Asian ginseng noted 1.5 grams per day was associated with greater reduction in HgbA1c and fasting glucose levels than either 2 or 3 grams per day. Another trial found, in subjects with well controlled type 2 diabetes, 6 grams per day of crude Asian ginseng rootlets improved the response to a glucose load, lowered fasting insulin levels, and increased insulin sensitivity scores, but did not improve HgbA1c.

Berberine is an alkaloid compound extracted from medicinal herbs such as goldenseal (Hydrastis canadensis), barberry (Berberis vulgaris), and Oregon grape (Mahonia aquifolium). Multiple clinical trials, research reviews, and meta-analyses of trials show berberine can improve blood glucose control and insulin sensitivity and decrease risks of cardiovascular and other complications in people with type 2 diabetes. Some evidence suggests it may also support healthy weight loss in people with diabetes. It has even been found to have comparable efficacy to conventional anti-diabetes drugs and to enhance the benefits these drugs when used in combination. Since it is poorly absorbed through the intestinal wall, some researchers have proposed berberine exerts its actions through positively impacting the gut microbiota. Researchers have typically used doses of 1–1.5 grams of berberine per day.

Like other berries and darkly pigmented fruits and vegetables, bilberry (Vaccinium myrtillus) is rich in polyphenolic compounds called anthocyanins. Laboratory and animal studies suggest bilberry and anthocyanins can improve glucose metabolism and insulin sensitivity through multiple actions, including reducing inflammation and oxidative stress, inhibiting carbohydrate-digesting enzymes, and improving the gut microbiome. Eating a diet high in anthocyanins has been consistently found to be associated with lower risk of type 2 diabetes, and clinical evidence shows anthocyanins from bilberry or other berries, especially when taken with meals, can improve blood glucose control and insulin sensitivity in people with type 2 diabetes. In one study, a single 470 mg dose of standardized bilberry extract (36% anthocyanins) before eating reduced the post-meal increase in blood glucose in subjects with type 2 diabetes. Bilberry and anthocyanins may also help to prevent and treat some diabetic complications. For example, a growing body of evidence suggests bilberry and anthocyanins can improve microvascular health and retinal function in people with diabetic retinopathy.

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. 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. Case reports suggest long-term treatment with high-dose biotin may reduce symptoms of diabetes-related nerve pain.

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.

Bitter melon (Momordica charantia) is a common vegetable in parts of Asia and has been used historically to treat diabetes. Constituents from bitter melon were shown to have anti-inflammatory activity and the ability to inhibit enzymes needed for carbohydrate breakdown and glucose absorption in the gut. Two meta-analyses that each included four trials found bitter melon had no significant effects on HgbA1c or blood glucose levels. A more recent meta-analysis that included ten trials found positive effects on glycemic control, but noted the evidence was primarily from low-quality studies. One placebo-controlled trial with 24 participants with type 2 diabetes found taking 2,000 mg of bitter melon per day for three months resulted in reductions in weight, body fat, waist circumference, and HgbA1c, and improved blood glucose control and insulin secretion in response to glucose. A ten-week trial with 95 participants with type 2 diabetes compared bitter melon extract (2,000 mg per day) to the anti-diabetes drug glyburide (DiaBeta®, 5 mg per day); bitter melon was more effective at lowering cardiac risk but not as effective at lowering blood glucose levels.

A number of randomized controlled trials have found adding 1 to 3 grams of cinnamon per day to usual treatment for two to three months can improve blood glucose control and lower HgbA1c in people with type 2 diabetes. However, not all studies have reported positive effects. Two meta-analysis of randomized controlled trials concluded that, although the evidence was difficult to analyze due to differences in study methods, cinnamon appears to lower blood glucose levels, but not HgbA1c, in people with type 2 diabetes.

Coenzyme Q10 (CoQ10) is an antioxidant that plays an important role in cellular energy production. People with type 2 diabetes have been found to have significantly lower blood levels of CoQ10 compared with healthy people. In multiple clinical trials, CoQ10 supplementation has been shown to lower blood glucose levels and HgbA1c, improve insulin sensitivity, and raise antioxidant status. Meta-analyses of randomized controlled trials have concluded that CoQ10 supplementation can improve blood glucose levels, HgbA1c, and cardiovascular risk factors in people with type 2 diabetes. Although it has been suggested that CoQ10 might help reduce diabetes complications through its antioxidant effects, one clinical trial found no benefit of CoQ10 in treatment of diabetes-related neuropathy. Doses of CoQ10 used in the research are 100–200 mg of CoQ10 per day.

Lagerstroemia speciosa, commonly known as crepe myrtle or banaba, grows in various tropical countries and Australia and has a history of use as a treatment for diabetes. Laboratory and preliminary clinical research suggests crepe myrtle and its active constituent corosolic acid may quickly lower blood glucose levels, inhibit carbohydrate breakdown and glucose absorption, and improve glucose and lipid metabolism. In a preliminary study that included people with type 2 diabetes, two weeks of treatment with 32 or 48 mg of a crepe myrtle extract standardized to contain 1% corosolic acid resulted in a fall in blood glucose levels averaging 20–30%, with a slightly better effect seen with the higher dose. Although these results are promising, additional studies are needed to demonstrate the long-term safety and efficacy of this herbal preparation.

Green tea is a rich source of antioxidant polyphenols called catechins, including the well-studied epigallocatechin gallate (EGCG). Through their anti-inflammatory and antioxidant effects, green tea catechins appear to protect cardiovascular health and improve metabolism in obesity, insulin resistance, and type 2 diabetes. Green tea consumption has been correlated with lower risk of type 2 diabetes and diabetes-related heart disease. In a preliminary trial, 400 mg per day of green tea extract standardized to contain 90% green tea polyphenols and 45% EGCG reduced arterial stiffness in subjects with type 2 diabetes. Although a meta-analysis of 17 randomized controlled trials, including a total of 1,133 subjects with various metabolic disorders, found that green tea consumption significantly improves blood glucose control and insulin sensitivity, another meta-analysis of six studies that only included participants with type 2 diabetes or pre-diabetes found no beneficial effects of green tea or green tea extract on insulin resistance or measures of glycemic control. Although an effective dose has not been identified, doses providing 800 mg of EGCG or more per day have been linked to liver injury and are not considered safe.

Gymnema has a long history of traditional use treating diabetes, and studies suggest gymnema and its active component, gymnemic acid, have anti-diabetes effects including reducing glucose absorption, stimulating the pancreas to produce insulin, and lowering triglyceride accumulation. So far, no double-blind trials have confirmed the efficacy of gymnema to treat diabetes. However, in preliminary studies, doses of 400 mg, 500 mg, and 1 gram per day of gymnema extract have been found to reduce blood glucose levels, increase insulin production, and improve markers of glycemic control in people with type 2 diabetes, in some cases allowing study participants to reduce their use of diabetes medications. Gymnema is not a substitute for insulin therapy, but insulin doses may need to be lowered while taking gymnema to avoid hypoglycemia.

Extracts from the leaf and seed of hairy basil (Ocimum canum), also known as Thai basil, have been found to reduce blood glucose, free radical, and cholesterol levels and increase the insulin response to glucose in animal models of type 2 diabetes. Long-term supplementation with 30 grams per day of hairy basil seeds improved glucose metabolism in a preliminary clinical trial in people with diabetes, and the study’s authors attributed the effect to the increase in dietary fiber.

Holy basil (Ocimim sanctum), also known as tulsi basil, has demonstrated positive effects in multiple studies using animal models of type 2 diabetes. A randomized controlled trial in people with type 2 diabetes found 2,500 mg of holy basil per day lowered blood glucose and cholesterol levels. Another pilot trial in overweight and obese youth found holy basil, at 500 mg per day for eight weeks improved glucose, insulin, triglyceride, and cholesterol levels, as well as markers of insulin resistance.

L-carnitine is an amino acid needed to properly utilize fat for energy. By supporting healthy fat metabolism, L-carnitine plays an important role in preserving normal insulin sensitivity and glycemic control. People with type 2 diabetes have been found to have lower levels of circulating L-carnitine than healthy people, and in people with type 2 diabetes, lower blood L-carnitine levels are correlated with higher blood glucose and triglyceride levels, lower free radical-quenching capacity, and greater risk of diabetes complications. Supplementing with L-carnitine has been shown in multiple human and animal studies to improve glucose tolerance and lipid metabolism in the context of insulin resistance. A meta-analysis of randomized controlled trials concluded 2–4 grams of L-carnitine per day can effectively reduce fasting blood glucose, total cholesterol, and LDL-cholesterol levels. Clinical trials further show the potential for 2–4 grams of L-carnitine per day to augment other therapies for improving metabolism in people with diabetes, including glimepiride, orlistat, sibutramine, simvastatin, and a low-calorie diet. In addition, a placebo-controlled trial found 600 mg per day of L-carnitine alleviated diabetes-related muscle cramps (a form of diabetic neuropathy) in people with type 2 diabetes.

An extract of milk thistle (Silybum marianum) called silymarin, at a dose of 140 mg three times per day, has been shown in placebo-controlled research to improve blood glucose, insulin, and triglyceride levels, and reduce HbA1c and markers of insulin resistance, oxidative stress and systemic inflammation in people with type 2 diabetes. In addition, preliminary research indicates a combination supplement containing silymarin and berberine (a compound found in several medicinal plants including goldenseal [Hydrastis canadensis]) may improve glycemic control and lipid metabolism in people with type 2 diabetes.

In a double-blind study, supplementation of middle-aged and elderly diabetics with a multiple vitamin and mineral preparation for one year reduced the risk of infection by more than 80%, compared with a placebo.

Onions have been used traditionally to treat diabetes. Animal studies suggest onion extracts may help reduce high blood glucose levels. Onion and its constituents have been shown in the laboratory to inhibit enzymes involved in the breakdown and digestion of starches and other carbohydrates, as well as enzymes involved in glucose metabolism. Onion has further been found to stimulate insulin responsiveness and glucose uptake by cells. Preliminary trials have found eating onions, in amounts of 60 and 100 grams (about 2 and 3.5 ounces) per day, lowered fasting blood glucose levels and the fasting response to glucose ingestion (glucose tolerance) in subjects with type 2 diabetes.

Preliminary research has suggested that pycnogenol may help lower blood glucose levels in people with type 2 diabetes. 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. 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.

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. 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.

Pinitol, a molecule related to inositol and found in high concentrations in soybeans, is believed to enhance the action of insulin. Placebo-controlled trials in participants with type 2 diabetes have found 1,200 mg of pinitol per day for 12–13 weeks decreased fasting blood glucose levels, improved insulin sensitivity, and lowered HbA1c. In another study, a single 1,200 mg dose of pinitol taken one hour prior to eating effectively lowered post-meal glucose levels in people with type 2 diabetes.

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 neuropathy after four weeks. 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. As a result, some doctors recommend that people with diabetic neuropathy supplement with vitamin B1, though the optimal level of intake remains unknown.

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 neuropathy after four weeks. 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. As a result, some doctors recommend that people with diabetic neuropathy supplement with vitamin B1, though the optimal level of intake remains unknown.

Multiple studies have reported finding an association between long-term metformin use in people with type 2 diabetes and vitamin B12 deficiency. Although this metformin-associated B12 deficiency does not appear to be linked to diabetic neuropathy (nerve dysfunction), it is nonetheless important to restore normal B12 status to avoid complications of B12 deficiency such as anemia, immune dysfunction, and neurological disorders.

Pyridoxal 5-phosphate (PLP), the active form of vitamin B6, is needed in the body for a wide array of metabolic processes. It also serves as an antioxidant and reduces formation of advanced glycation end-products (AGEs), which cause widespread damage to proteins and DNA. Laboratory and animal research suggests PLP inhibits enzymes involved in carbohydrate digestion and absorption, resulting in lower spikes in blood glucose levels after eating. Many people with diabetes have low blood levels of PLP, and levels are even lower in people with diabetes complications such as nerve damage (neuropathy) and kidney damage (nephropathy). In a preliminary trial, subjects with neuropathy due to type 2 diabetes were treated with 35 mg of PLP, along with 3 mg of methylfolate and 2 mg of methylcobalamin (B12), twice per day for four weeks, followed by the same regimen once per day for the rest of a full year. Nerve function was significantly improved after six months and further improved after one year of treatment. This same combination of B vitamins was found helpful in people with mild-to-moderate type 2 diabetes-related retinopathy after six months.

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. 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.

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. In addition, like other antioxidants, vitamin C reduces formation of advanced glycation end-products (AGEs), which cause widespread damage to proteins and DNA. 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. Furthermore, low vitamin C levels in blood and in the eye have been correlated with increased risk of retinopathy. 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.

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. 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.

A preliminary trial supplementation with about 2,000 IU of vitamin D per day for 3 months significantly improved pain by almost 50% in patients with diabetic neuropathy.

Vitamin D is now recognized as necessary for healthy immune function, regulation of inflammatory processes, insulin production, and cellular responsiveness to insulin. Vitamin D deficiency has been linked to high blood glucose levels, insulin resistance, type 2 diabetes, and diabetes complications. 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. 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.

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.

People with low blood levels of vitamin E are more likely to develop type 1 and type 2 diabetes. Vitamin E supplementation has improved glucose tolerance in people with type 2 diabetes in most, but not all, double-blind trials. Vitamin E has also improved glucose tolerance in elderly people without diabetes. Three months or more of at least 900 IU of vitamin E per day may be required for benefits to become apparent.

In one of the few trials to find vitamin E supplementation ineffective for glucose intolerance in people with type 2 diabetes, damage to nerves caused by the diabetes was nonetheless partially reversed by supplementing with vitamin E for six months. Animal and preliminary human data indicate that vitamin E supplementation may protect against diabetic retinopathy and nephropathy, 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, although not all, studies.

In one report, vitamin E was found to impair glucose tolerance in obese patients with diabetes. The reason for the discrepancy between reports is not known.

Vitamin E appears to lower the risk of cerebral infarction, a type of stroke, in people with diabetes who smoke. A review of a large Finnish study of smokers concluded that smokers with diabetes (or hypertension) can benefit from small amounts of vitamin E (50 IU per day).

People with low blood levels of vitamin E are more likely to develop type 1 and type 2 diabetes. Vitamin E supplementation has improved glucose tolerance in people with type 2 diabetes in most, but not all, double-blind trials. Vitamin E has also improved glucose tolerance in elderly people without diabetes. Three months or more of at least 900 IU of vitamin E per day may be required for benefits to become apparent.

In one of the few trials to find vitamin E supplementation ineffective for glucose intolerance in people with type 2 diabetes, damage to nerves caused by the diabetes was nonetheless partially reversed by supplementing with vitamin E for six months. Animal and preliminary human data indicate that vitamin E supplementation may protect against diabetic retinopathy and nephropathy, 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, although not all, studies.

In one report, vitamin E was found to impair glucose tolerance in obese patients with diabetes. The reason for the discrepancy between reports is not known.

Vitamin E appears to lower the risk of cerebral infarction, a type of stroke, in people with diabetes who smoke. A review of a large Finnish study of smokers concluded that smokers with diabetes (or hypertension) can benefit from small amounts of vitamin E (50 IU per day).

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. 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). 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.

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. 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.

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. 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.

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.

Açai berry is reported to be a traditional remedy for diabetes. A pilot trial in ten overweight but otherwise healthy adults found taking 100 grams of açai pulp per day for one month led to decreases in fasting glucose and insulin levels as well as after-meal blood glucose, triglyceride, total cholesterol, and LDL-cholesterol levels. Positive metabolic and anti-diabetic effects have been demonstrated in animal models of type 2 diabetes. Clinical trials evaluating açai’s effect in people with type 2 diabetes are needed.

Amylase inhibitors are substances that reduce the activity of amylase, the digestive enzyme required to break down dietary starches into absorbable glucose. Many plants and plant foods, including vegetables and legumes, contain amylase-inhibiting compounds that may be useful in preventing and treating type 2 diabetes. For example, adding beans to a serving of rice reduces the rise in blood glucose, an effect that may be due in part to the amylase-inhibiting action of beans. A review of clinical trials reported that taking 1,500 to 3,000 mg of an amylase-inhibiting extract from white beans (Phaseolus vulgaris) before meals has been shown in multiple studies to reduce post-meal blood glucose levels and may promote weight loss. However, this review and most of the studies it included were funded by the manufacturer of the bean extract. Its usefulness as a therapy for type 2 diabetes has not been tested.

Preliminary research has identified a correlation between drinking either regular or decaffeinated coffee and reduced risk of type 2 diabetes. Test tube studies suggest that chlorogenic acid, a primary constituent found in coffee and in unroasted green coffee extract, may inhibit glucose production by the liver, which could theoretically lead to lower blood glucose levels. An animal study found that green coffee extract also prevented the reduction in insulin sensitivity caused by a high-fat diet. A double-blind trial found that healthy people who drank a sweetened coffee beverage containing green coffee extract (providing 400 to 450 mg of chlorogenic acids) had lower blood glucose levels during the following two hours compared to when they drank the same coffee beverage without added green coffee extract. However, no trials in people with type 2 diabetes have been performed.

Evening primrose oil is a source of the anti-inflammatory omega-6 fatty acid gamma linolenic acid (GLA). Animal research suggests evening primrose oil and GLA may be helpful for preventing and treating diabetic neuropathy. Supplementing with 4 grams of evening primrose oil per day for six months was found in a double-blind trial to improve nerve function and to relieve pain symptoms of diabetic neuropathy. However, the principal investigator who conducted these clinical trials was subsequently found by the professional conduct committee of the General Medical Council (United Kingdom) to have falsified the results of the research. Therefore, it is not clear whether evening primrose oil or GLA is of any value for patients with diabetic neuropathy.

Fish oil and its polyunsaturated omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been widely studied for their potential metabolic benefits. Clinical trials have reported conflicting evidence, with some studies finding positive effects, some no effects, and some negative effects of fish oil consumption on markers of metabolic health in people with type 2 diabetes. Attempting to explain these inconsistencies, one analysis suggested omega-3 fatty acids may be more beneficial in women than men. Nevertheless, a large meta-analysis that pooled findings from 45 randomized controlled trials with a combined total of 2,674 participants with type 2 diabetes found an overall positive effect of omega-3 fatty acids from fish on levels of markers of systemic inflammation, triglycerides, total cholesterol, LDL-cholesterol, and VLDL-cholesterol levels, as well as a small but statistically significant positive effect on HbA1c. Another meta-analysis of 17 studies with a total of 672 participants found omega-3 fatty acids from fish could improve insulin sensitivity in people with metabolic disorders, including type 2 diabetes.

The gut microbiome is now recognized as an important target for anti-diabetes therapies, with its ability to impact carbohydrate and fat metabolism and regulate inflammatory activity in the body. Prebiotic fibers like fructo-oligosaccharides promote the growth of gut bacterial colonies associated with healthy metabolic function. A review of 27 clinical trials investigating the effects of prebiotics in people with type 2 diabetes reported the majority (74%) of studies found beneficial results on metabolic and/or inflammatory markers, including blood glucose and lipid levels. The best evidence was for fructo-oligosaccharides, with fewer trials performed using other prebiotics. A meta-analysis that included six randomized controlled trials using prebiotics in people with type 2 diabetes found there was a significant positive effect on fasting blood glucose levels, HbA1c, and lipid profiles. Prebiotic supplements used in the research provided 10–20 grams of fructo-oligosaccharides per day.

Ginkgo (Ginkgo biloba) extract was found in a placebo-controlled trial to enhance the HbA1c-lowering effect of the widely used anti-diabetes drug metformin, while not directly altering metabolism of the drug. In another placebo-controlled trial that included participants whose type 2 diabetes was not well controlled by metformin, adding 120 mg per day of ginkgo resulted in greater reductions in HbA1c and fasting blood glucose and insulin levels, as well as body-mass index (BMI), waist circumference, and abdominal fat, after 90 days. Clinical research has shown ginkgo extract can improve kidney function in people with type 2 diabetes and early signs of nephropathy (kidney damage), and strengthen retinal blood flow in those with diabetic retinopathy (damage to the visual center of the eye). Treatment with the combination of ginkgo leaf plus a traditional Chinese herbal remedy (Liuwei Dihuang Pills) reduced the risks of developing retinopathy or nephropathy in a placebo-controlled trial that included 140 people with type 2 diabetes who were monitored for three years. Findings from animal studies suggests ginkgo may also have protective effects on nerve tissue and may be helpful in preventing and treating type 2 diabetes-related neuropathy (nerve dysfunction).

In a preliminary trial, supplementation with 1 gram per day of berberine (one of the active compounds in goldenseal) for two months significantly lowered blood glucose levels in patients with type 2 diabetes.

Hibiscus has a history of use in treating diabetes. Laboratory studies show hibiscus and some of its active constituents have anti-diabetic effects, including enhancing the metabolic response to insulin and inhibiting enzymes that facilitate carbohydrate digestion and glucose absorption. Its potential to improve glycemic control and reduce production of advanced glycation end-products (AGEs, damaged molecules that cause cell and tissue injury) has been demonstrated in animal models of type 2 diabetes. In humans, drinking hibiscus tea two to three times per day for one month was found to improve lipid levels and reduce high blood pressure in subjects with type 2 diabetes. Hibiscus tea is usually made by infusing 1 to 2 teaspoons (3 to 6 grams) of dried flower into 1 cup (250 ml) of hot water.

Disturbances in inositol metabolism are thought to be an underlying factor in insulin resistance and type 2 diabetes. Animal studies suggest inositol may reduce glucose absorption in the digestive tract and have insulin-like effects, increasing glucose uptake and utilization by cells. A pilot trial examined the effects of adding inositol in people with type 2 diabetes with persistently high HbA1c despite medical treatment. A supplement providing two types of inositol (550 mg of myo-inositol and 13.8 mg of D-chiro inositol per day) was added to their treatment. After three months, fasting blood glucose levels and HbA1c had decreased significantly. Reviews of clinical research have shown that inositol can improve glucose metabolism and insulin sensitivity in women with polycystic ovarian syndrome (PCOS), a condition marked by hormonal imbalance and increased risk of insulin resistance, type 2 diabetes, and cardiovascular disease.

Manganese is an important nutrient for the activation of antioxidant and metabolic enzyme systems. Both high and low manganese levels can contribute to increased oxidative stress and the development and progression of type 2 diabetes. Animal and laboratory research suggest manganese supplementation might improve insulin sensitivity and protect blood vessels from damage due to high glucose levels in people with type 2 diabetes. Although clinical trials are lacking, taking a multivitamin/mineral supplement to ensure adequate manganese intake is a reasonable precautionary measure for people with type 2 diabetes.

Medium-chain triglycerides (MCT) contain fatty acids that have six to twelve carbon units and are found mainly in coconut and palm oils. Studies in which people with type 2 diabetes replaced usual long-chain fatty acid sources with MCT oils indicate its potential benefits. In a pilot trial, getting 31% of per day calories from MCTs for five days led to reduced post-meal blood glucose levels and appeared to strengthen insulin sensitivity in people with type 2 diabetes. Other preliminary research noted 30 days of getting 18% of per day calories from MCTs led to slight improvement in post-meal blood glucose control but no other measurable changes in glucose metabolism. A controlled trial found moderately overweight people with type 2 diabetes who took 18 grams per day of MCTs for 90 days had decreased insulin resistance, greater weight loss, and more reduction in waist circumference than those who took long-chain triglycerides.

Mistletoe plants have been used traditionally to treat diabetes. Alcohol extracts from various mistletoe plants, including Viscum and Plicosepalus species, have been shown to stimulate pancreatic insulin production and release and improve glucose metabolism in animal models of type 2 diabetes. One such study found a water extract of mistletoe was not as effective as the alcohol extract.

Moringa (Moringa oleifera) leaf extract has a history of traditional use in treating diabetes. Findings from animal studies lend support for its potential benefits and suggest its effects may be due in part to its ability to inhibit enzymes involved in carbohydrate digestion and glucose absorption. A study in healthy adults showed moringa leaf, at doses of 1 gram, 2 grams, and 4 grams, stimulated insulin release, with greater effect as dose increased. However, a pilot trial that included 32 participants with type 2 diabetes found 8 grams of moringa leaf per day had no effect on blood glucose control.

In a placebo-controlled trial, 79 subjects with type 2 diabetes received 500 mg per day of olive leaf extract or placebo. After 14 weeks, those who received the olive leaf extract had lower fasting blood insulin levels and HbA1c, but no difference in post-meal insulin levels was seen. The same researchers also reported finding olive leaf extract inhibited starch digestion and glucose absorption in animals with experimental diabetes. On the other hand, 100 mg per day of olive leaf extract, in combination with fenugreek and bergamot extracts, was no better than placebo at restoring healthy glucose metabolism in a trial with 100 participants with prediabetes. Another trial included people with prediabetes who received either olive leaf tea of a control tea three times per day for 12 weeks. Olive leaf tea reduced fasting blood glucose levels and improved lipid levels. In overweight men at risk for developing type 2 diabetes, a high-polyphenol olive leaf extract (providing 51.1 mg of oleuropein and 9.7 mg of hydroxytyrosol per day) improved insulin sensitivity and pancreatic function after 12 weeks. More research in subjects with type 2 diabetes is needed.

Quercetin, a flavonoid widely found in the plant world, has well established antioxidant and anti-inflammatory properties. Higher dietary intake of quercetin has been correlated with a lower risk of type 2 diabetes in one study. Animal and laboratory research suggests quercetin may have a role to play in improving metabolism in type 2 diabetes and protecting against diabetes complications. A topical quercetin preparation, which also contains vitamins C and D, was found in a human clinical trial to be effective for relieving symptoms of neuropathy related to type 2 diabetes.

Multiple studies using experimental and animal models of type 2 diabetes have reported anti-diabetes effects of reishi mushroom (Ganoderma lucidum) and its constituents. However, in a placebo-controlled trial with 84 participants, 3 grams per day of reishi mushroom for 16 weeks had no effect on glycemic control or any metabolic markers in people with type 2 diabetes.

Taurine is an amino acid that affects glucose and lipid metabolism by acting as an antioxidant and participating in regulation of insulin secretion and action. Low taurine levels have been linked to type 2 diabetes and other metabolic disorders, and animal studies suggest taurine supplementation may protect against diabetes complications. Few studies of taurine supplementation in people with type 2 diabetes have been performed, and these have yielded mixed results; one clinical trial indicated the effects of taurine on metabolism may be determined partly by genetics.

Clinical trials using the vanadium salt vanadyl sulfate, in doses of 100 mg to 150 mg per day, indicate it may improve glucose control and insulin sensitivity in people with type 2 diabetes. Over a six-week period, a small group of people with type 2 diabetes were given 75 mg, 150 mg, or 300 mg of vanadyl sulfate (about 25–100 mg elemental vanadium) per day. Only in the groups receiving 150 mg or 300 mg was glucose metabolism improved and fasting blood glucose levels and HbA1c decreased; however, these higher doses cause digestive disturbances and were associated with reductions in beneficial HDL-cholesterol levels. Other forms of vanadium, such as a vanadium-maltol complex, also appear to improve glycemic control and are being explored for their safety.

Vitamin B3 (niacin) is an important nutrient for regulating lipid metabolism and has well established positive effects on cholesterol and triglyceride levels. High dietary intake of niacin may protect against diabetes-related fatty liver. Unfortunately, the intake of therapeutic amounts of niacin, such as 2 to 3 grams per day, has been associated with an increased risk of type 2 diabetes and worsening of blood glucose control in people with diabetes. A microencapsulated niacin (but not niacinamide) product, however, was found in a pilot trial to improve insulin sensitivity in men with obesity, possibly by altering the gut microbiome. The potential benefits of microencapsulated niacin in type 2 diabetes remain to be investigated.

In a preliminary trial, consumption of mate (Ilex paraguariensis) tea in the amount of 330 ml (about 12 ounces) 3 times per day for 60 days improved measures of blood glucose control in patients with type 2 diabetes.