Diabetes

Diabetes

Diabetes

DIABETES

Synopsis:
Background
Risk Factors
Nutritional Support for Diabetes
Suggested Supplementation
References

 

Diabetes is caused by abnormal metabolism of glucose, either because the body does not produce enough insulin or because the cells become desensitized to the effects of insulin.  Possible complications in diabetes include damage to eyes, nerve tissue, kidneys, blood vessels and cardiovascular system, and painful peripheral nerve damage.  Most practitioners focus treatment on blood sugar control. This simplified approach can actually hasten the progression of diabetes and does not address the damage it causes.

A new approach to diabetes and treatment is needed. Over the past 20 years, the number of adults diagnosed with diabetes has more than doubled, and children are being diagnosed with diabetes in alarming numbers. Diabetes has rapidly emerged as a leading culprit in heart disease, as well as being a leading cause of amputation and blindness among adults.

It is important for us to understand the ways in which blood glucose causes damage and take steps to prevent and interrupt these processes. The most notorious process is glycation (i.e., sugar molecules reacting with proteins to produce non-functional structures in the body). Glycation compromises proteins throughout the body, thus is a key feature of diabetes-related complications (e.g., nerve damage, heart attack, and blindness).  We must try to protect the body from glycation damage.

Oxidative stress is also central to the damage caused by diabetes. Diabetics suffer from high levels of free radicals that damage arteries throughout the body.  Antioxidant therapy is needed to help reduce oxidative stress and lower the risk of diabetic complications.

 

 

BACKGROUND

Insulin is a hormone responsible for transporting glucose into cells. When there is excess glucose in the blood, insulin is secreted from the pancreas and signals the liver and muscles to store glucose as glycogen. Insulin also stimulates adipose tissue to store glucose as fat for long-term energy reserves. Insulin receptors are found in all cells throughout the body. In a healthy person, blood glucose levels are extremely stable (Kumar 2005). Normal fasting glucose levels range between 70 and 100 mg/dL.

Difference between Type 1 And Type 2 Diabetes

Type 1 diabetes. Type 1 diabetes, formerly known as insulin-dependent diabetes, is an autoimmune condition that occurs when the body attacks and destroys the cells (beta-cells or β-cells) that make insulin. Type 1 diabetes accounts for about 5 – 10 % of cases. Because type 1 diabetics can no longer make insulin, insulin replacement therapy is essential.

Type 2 diabetes. Type 2 diabetes, formerly known as non-insulin-dependent diabetes, occurs when the body is no longer able to use insulin effectively and gradually becomes resistant to its effects. It is a slowly progressing disease. In the early stages, both insulin and glucose levels are elevated (conditions called hyperinsulinemia and hyperglycemia, respectively). In the later stages, insulin levels drop, and blood glucose levels are very elevated. Therapy for type 2 diabetes should be tailored to the stage of the disease.

 

The Diabetes Damage Cascade

Glycation and oxidative stress are central to the damage caused by diabetes. Unfortunately, conventional treatment for diabetes generally does not address these.

Glycation occurs when glucose reacts with protein, resulting in sugar-damaged proteins called advanced glycation end products (AGEs) (Kohn 1984; Monnier 1984). A measure of blood glucose control that is called HbA1c is actually a measurement of glycated hemoglobin in our blood.

Glycated proteins damage cells in numerous ways, including impairing cellular function, which induces the production of inflammatory cytokines (Wright 2006) and free radicals (Forbes 2003; Schmidt 2000). In animal studies, inhibiting glycation protects against damage to the kidney, nerves, and eyes (Forbes 2003; Sakurai 2003). In a large human trial, each 1 % reduction in HbA1c correlated with a 21 % reduction in risk for any complication of diabetes, a 21 % reduction in deaths related to diabetes, a 14 % reduction in heart attack, and a 37 % reduction in microvascular complications (Stratton 2000).

High levels of blood glucose and glycation also produce free radicals that further damage cellular proteins (Vincent 2005) and reduce nitric oxide levels. Nitric oxide is a potent vasodilator that helps keep arteries relaxed and wide open. Oxidative stress in diabetes is also linked to endothelial dysfunction, the process that characterizes atherosclerotic heart disease. According to studies, diabetes encourages white blood cells to stick to the endothelium (i.e., the thin layer of cells that line the inside of arteries). These white blood cells cause the local release of pro-inflammatory chemicals that damage the endothelium, accelerating atherosclerosis (Lum 2001). Diabetes is closely associated with severe coronary heart disease and increased risk of heart attack.

 

Symptoms of Diabetes

These may include:

  • Increased thirst and urination
  • Unusual weight changes
  • Irritability and fatigue
  • Blurry vision
  • Dark outgrowths of skin (skin tags) may also appear.

 

The Truth about Type 2 Diabetes Therapy

Type 2 diabetics are routinely told they need to boost their insulin levels, which will help drive blood glucose into their cells and lower their blood glucose levels. Unfortunately, this defies common sense because in the early stages of type 2 diabetes, insulin levels are already elevated (hyperinsulinemia). This is because the problem is not with insulin production; rather, a metabolic defect of insulin utilization. The delicate insulin receptors on cell membranes are less responsive to the insulin than are the receptors of people without type 2 diabetes, which means that less glucose is absorbed from the blood stream than would be normally, and glucose levels slowly rise.

This elevation in glucose upsets the body’s natural balance, prompting the pancreas to discharge large amounts of insulin to normalize glucose levels. Eventually, the fragile insulin receptors become less sensitive (insulin resistant), which means that the pancreas must secrete even more insulin to keep clearing the blood of glucose. In later stages of the disease, the pancreas becomes “burned out” and can no longer produce adequate insulin.

Unfortunately, many diabetics are prescribed drugs (e.g., sulfonylureas) designed to boost insulin levels, which may actually serve to hasten the disease. Also, insulin itself is a powerful hormone that, in high levels, can inflict damage. Evidence suggests that high levels of insulin may suppress growth hormone synthesis and release among obese and overweight people (who are prone to hyperinsulinemia) (Luque 2006).

Early Stage Treatment

In the early stages of the disease, people suffer from both high blood glucose and high insulin levels.  Rather than take drugs that further increase the level of insulin in the blood, people with type 2 diabetes would do better to increase the sensitivity of insulin receptors on the cell membranes.

One of the best defenses is improved diet and exercise. Although the disease has a genetic component, many studies have shown that diet and exercise can prevent it (Diabetes Prevention Program Research Group 2002; Diabetes Prevention Program Research Group 2003; Muniyappa 2003; Diabetes Prevention Program Research Group 2000). Just 30 minutes a day of moderate physical activity, coupled with a 5 to 10 % reduction in body weight, produces a 58 % reduction in the incidence of diabetes among people at risk (Sheard 2003). A diet high in fiber, unrefined carbohydrates, and low in saturated fat and low in glycemic index is recommended (Sheard 2004).

A healthy diet for diabetics is also rich in potassium. Potassium improves insulin sensitivity, responsiveness, and secretion. A high potassium intake also reduces the risk of heart disease, atherosclerosis, and cancer. Insulin administration induces potassium loss (Khaw 1984; Norbiato 1984).

Obese people have a far greater tendency to develop type 2 diabetes than slim people. Therefore, weight loss accompanied by increased exercise and a healthy diet is effective for diabetes prevention and treatment (Mensink 2003; Sato 2000; Sato 2003).

 

Metformin: Increasing Insulin Sensitivity

In addition to diet and exercise, the prescription drug metformin has been proven to increase insulin sensitivity in people with mild to moderate hyperglycemia. Metformin is now the most commonly prescribed oral antidiabetic drug worldwide. It works by increasing insulin sensitivity in the liver (Joshi 2005). It also has a number of other beneficial effects, including weight loss, reduced cholesterol-triglyceride levels, and improved endothelial function.

Metformin is better tolerated than many other anti-diabetic prescription drugs, but people with congestive heart failure, kidney or liver disease are not candidates for metformin therapy. Neither are people who consume alcohol in excess. Vitamin B12 levels should also be checked regularly because chronic use of metformin can cause a folic acid and B12 deficiency, resulting in neurological impairment and disruption in homocysteine clearance.

Many other nutrients have been shown to increase insulin sensitivity, protect vulnerable cell membranes, and reduce the damaging effects of elevated glucose (see “Nutritional Supplementation for Diabetics” below). Ideally, a combination of improved diet, exercise, supplementation, and insulin-sensitizing prescription medication can reverse mild to moderate hyperglycemia before stronger medications are needed and permanent damage is done.

 

RISK FACTORS

Aging, obesity, family history, physical inactivity, ethnicity, and impaired glucose metabolism.

Type 2 diabetes is also a prominent risk of metabolic syndrome, a constellation of conditions that includes insulin resistance along with hypertension, lipid disorders, and overweight.

 

NUTRITIONAL SUPPORT FOR DIABETES

Certain nutrients can counteract the progression of their disease by improving insulin sensitivity, enhancing glucose metabolism, and mitigating the complications of diabetes.  

Antiglycation Agents

Advanced glycation end products (AGEs) form when sugars bond with proteins, lipids, and nucleic acids. This process contributes to the toxic effects of high blood sugar (Uribarri 2010; Ceriello 2012). Fortunately, several nutrients can counter these processes.

Benfotiamine

Diabetes and obesity often induce a relative thiamine (vitamin B1) deficiency, which contributes to some of the damaging consequences of hyperglycemia (Beltramo 2008; Page 2011; Via 2012). Benfotiamine is a fat-soluble derivative of thiamine that has much greater bioavailability than other forms of thiamine, and is capable of reaching concentrations in the bloodstream several times that of orally administered thiamine (Greb 1998; Xie 2014). This unique form of vitamin B1 inhibits AGE formation, inflammation, and oxidative stress (Hammes 2003; Du 2008; Balakumar 2010; Shoeb 2012).

A clinical trial in 165 patients with diabetic neuropathy found benfotiamine supplementation for six weeks reduced diabetic neuropathy pain. The benefits were clearer in subjects who consumed 600 mg of benfotiamine daily compared with those who took 300 mg, and in those who took benfotiamine for a longer period of time (Stracke 2008).

Clinical and animal studies have demonstrated the efficacy of benfotiamine in the treatment of diabetes-related neuropathy, kidney disease, peripheral vascular disease, and retinopathy (Stirban 2006; Chakrabarti 2011; Stracke 1996; Simeonov 1997; Winkler 1999; Haupt 2005; Nikolic 2009).

Carnosine

The peptide carnosine is capable of inhibiting formation of AGEs and even reversing protein glycation (Boldyrev 2013; Seidler 2004). In a study on diabetic mice, carnosine supplementation increased plasma levels of carnosine 20-fold, reduced triglyceride levels by 23%, and increased stability of atherosclerotic lesions (Brown 2014). Carnosine has also been shown to improve the ability of cells to survive in the presence of high glucose concentrations, and improve wound healing in diabetic animals (Ansurudeen 2012). An animal model of diabetes showed carnosine supplementation improved the ability of red blood cells to change their shape as necessitated by mechanical forces encountered during blood flow; this process is impaired in diabetes, contributing to diabetic complications (Yapislar 2012).

Pyridoxal 5’-phosphate

Pyridoxal 5’-phosphate is the active form of vitamin B6 and an effective anti-glycation agent (Nakamura 2007; di Salvo 2012). Treating 20 type 2 diabetics with 35 mg pyridoxal 5’-phosphate along with 3 mg activated folate and 2 mg vitamin B12 improved skin sensation in diabetic peripheral neuropathy (Walker 2010). Supplementation with pyridoxal 5’-phosphate significantly decreased high concentrations of glycation-induced toxic compounds in diabetic rats, and prevented the progression of diabetic neuropathy (Higuchi 2006; Nakamura 2007).

In addition to preventing protein glycation, pyridoxal 5’-phophate is one of the most effective inhibitors of lipid (fat) glycation. Lipid AGEs are elevated in diabetic patients compared with healthy controls, and accumulation of lipid AGEs contributes to vascular diseases related to diabetes and aging (Miyazawa 2012; Bucala 1993).

 

Phytochemical AMPK Activators

AMPK (adenosine monophosphate-activated protein kinase) is a critical energy sensor in the body. Activation of AMPK helps regulate energy metabolism, increasing fat burning and glucose utilization while blocking fat and cholesterol synthesis (Coughlan 2014; Park, Huh 2014). AMPK activation is a mechanism by which the preeminent antidiabetic drug metformin exerts some of its well-known metabolic benefits (Choi 2013; Yue 2014).

Gynostemma pentaphyllum

Gynostemma pentaphyllum (G. pentaphyllum) is native to Asian countries including Korea, China, and Japan, where it is used as tea and in traditional medicine. Like metformin, gynostemma extract activates AMPK (Park, Huh 2014).

In animal and human cell cultures, extracts from G. pentaphyllum have been shown to improve insulin sensitivity, reduce levels of glucose and cholesterol, enhance immune function, and inhibit cancer growth (Lu 2008; Yeo 2008; Megalli 2006; Liu, Zhang, 2014). In a randomized controlled trial, an extract from gynostemma modestly reduced body weight and fat mass in obese subjects (Park, Huh 2014). Results from another trial found gynostemma tea improved insulin sensitivity, and lowered fasting glucose nearly ten times more than placebo (Huyen 2013).

In a clinical trial involving 25 diabetics, a gynostemma extract was tested as add-on therapy to the sulfonylurea drug gliclazide. Reductions in plasma glucose and HbA1C were nearly three times greater in the gynostemma extract group compared with placebo. Gynostemma acted by increasing insulin sensitivity rather than stimulating insulin release. It also prevented weight gain and hypoglycemia, which are often associated with sulfonylurea drugs (Huyen 2012).

In a trial in participants with non-alcoholic fatty liver disease, a condition strongly linked to insulin resistance, treatment with gynostemma extract, as an adjunct to diet, resulted in a significant reduction in liver enzymes and insulin levels, a decrease in body mass index, and increased insulin sensitivity (Chou 2006; Utzschneider 2006).

Trans-tiliroside

Trans-tiliroside, a flavonoid derived from plants such as rose hips, can activate AMPK. Animal studies and laboratory experiments using human cells have demonstrated that trans-tiliroside exerts anti-obesity and antidiabetic effects including increased fat burning (particularly visceral fat), reduced blood levels of insulin and fats, and decreased after-meal glucose and insulin spikes. Trans-tiliroside also enhanced adiponectin signaling; adiponectin is a key hormone that counters insulin resistance (Goto, Horita 2012; Goto, Teraminami 2012; Shi 2011).

A laboratory study of insulin-resistant human liver cells found trans-tiliroside boosted cellular glucose consumption compared with the antidiabetic drug metformin (Zhu 2010). In mouse models of diabetes, daily oral administration of trans-tiliroside reduced fasting blood sugar by up to nearly 30% after 15 days of treatment, while diabetic mice treated with metformin had a near 23% reduction (Qiao 2011).  Supplemented animals also had significant reductions in serum triglycerides and total cholesterol, and an increase in HDL cholesterol. In a study in obese subjects, 40 g of rose hip powder daily for six weeks significantly lowered systolic blood pressure and plasma cholesterol levels (Andersson 2012).

Green tea extract

Green tea extract, a major constituent of which is epigallocatechin-3-gallate (EGCG), has been shown to reduce glucose and insulin levels and improve insulin sensitivity. In a rodent model of accelerated aging, EGCG supplementation lowered glucose and insulin levels. EGCG also increased insulin sensitivity, decreased liver fat accumulation, and improved markers of mitochondrial function (Liu, Chan 2015). In animal models of diabetes, green tea has been shown to protect against diabetic retinopathy (Silva 2013; Kumar 2012).

In a 16-week randomized controlled trial in 92 subjects with type 2 diabetes and blood lipid abnormalities, participants took 500 mg green tea extract three times daily. The green tea group showed significant increases in insulin sensitivity and HDL cholesterol levels, as well as a significant decrease in serum triglycerides (Liu, Huang, 2014). A two-month trial in 103 healthy postmenopausal women found a significant difference in glucose and insulin levels between a group that took up to 800 mg EGCG per day and a placebo group. Glucose and insulin levels fell in the EGCG group, but rose in the placebo group (Wu 2012). At the end of a four-week trial of catechin-rich green tea in 22 postmenopausal women, those in the green tea group had significantly lower postprandial glucose and significantly better after-meal oxidative stress parameters (Takahashi 2014).

Elevated blood pressure is one of the characteristic cardiovascular risk factors often found in diabetics and prediabetics. A randomized controlled trial administered daily a green tea extract powder containing a total of 544 mg polyphenols to 60 prediabetic subjects. This led to significantly reduced HbA1C and diastolic blood pressure (Fukino 2008). Similarly, a trial in overweight or obese middle-aged men found 800 mg EGCG daily significantly reduced diastolic blood pressure (Brown 2009).

Among additional possible mechanisms underlying green tea’s benefits are suppression of inflammatory genes and mitigation of oxidative damage (Uchiyama 2013; Jang 2013; Yang 2013). Also, green tea, black tea (a rich source of theaflavin polyphenols), and oolong tea have been reported to inhibit the alpha-glucosidase enzyme, causing less carbohydrate to be digested and absorbed (Satoh 2015; Yang 2015; Oh 2015). Other evidence suggests green tea constituents may activate AMPK (Liu, Chan 2015).

Bilberry extract

Closely related to blueberry, bilberry is rich in polyphenols and anthocyanins. In a study in diabetic mice, a bilberry extract reduced blood glucose and enhanced insulin sensitivity by activating AMPK (Ogawa 2014; Takikawa 2010). Bilberry polyphenols also have potent anti-inflammatory and free radical-scavenging actions (Subash 2014; Kolehmainen 2012). Bilberry has also been shown in animal studies to combat diabetic retinopathy (Kim, Kim 2015); and a clinical study in 180 type 2 diabetics showed that bilberry, in combination with several other micronutrients, improved measures of ocular health and visual acuity in subjects with preclinical or early diabetic retinopathy (Moshetova 2015).

In a preliminary controlled trial in eight type 2 diabetic males, a concentrated bilberry extract significantly lowered after-meal glucose and insulin levels compared with placebo. Reduced rates of carbohydrate digestion and absorption likely accounted for these effects. Specifically, bilberry polyphenols may have inhibited the action of alpha-glucosidase, preventing the breakdown of carbohydrates into glucose (Hoggard 2013).

 

Prevention of Exaggerated Post-Meal Blood Glucose Elevations

Several natural compounds can help prevent post-meal surges in blood glucose. Among the mechanisms that natural substances target to allow tighter control of post-meal glucose levels are alpha-glucosidase inhibition, alpha-amylase inhibition, SGLT1 inhibition, and sucrase inhibition (Van de Laar 2005; Matsuo 1992; Melzig 2007; Kinne 2011; Lee 1982).

(a) Alpha-glucosidase inhibition

The alpha-glucosidase enzymes in the intestine break down carbohydrates into simple sugars so they can be absorbed. Inhibiting alpha-glucosidase reduces the amount of simple sugars available for absorption, mitigating postprandial glucose surges (Tundis 2010).

White mulberry leaf extract

White mulberry leaf has a long history of use in traditional Chinese medicine for preventing and treating diabetes (Mudra 2007). A component of white mulberry, called 1-deoxynojirimycin, impedes the action of alpha-glucosidase, slowing carbohydrate absorption and preventing post-meal blood sugar spikes (Banu 2015; Naowaboot 2012; Nakanishi 2011). This effect of the white mulberry leaf extract has been demonstrated in healthy subjects, type 2 diabetics, and those with impaired glucose tolerance (Asai 2011; Banu 2015; Mudra 2007).

A 4-week randomized controlled trial in 36 subjects with impaired fasting glucose found white mulberry leaf extract significantly reduced post-meal glucose and insulin levels (Kim, Ok 2015). A trial in 24 subjects with type 2 diabetes compared a white mulberry leaf product to the sulfonylurea drug glyburide. White mulberry decreased total cholesterol by 12%, LDL cholesterol by 23%, and triglycerides by 16%; raised HDL cholesterol by 18%; and reduced fasting blood glucose and oxidative stress markers. Glyburide only slightly improved glycemic control and triglycerides (Andallu 2001). A clinical study in healthy volunteers found that 1-deoxynojirimycin-enriched white mulberry powder suppressed post-prandial blood glucose surge and lowered insulin levels (Kimura 2007).

Green coffee bean extract. Epidemiologic studies have linked coffee consumption with reduced risk of type 2 diabetes, Alzheimer disease, Parkinson disease, and certain cancers. This association may be explained by the chlorogenic acid content of coffee (Song 2014; Ong 2012; Meng, Cao 2013). Chlorogenic acid, a polyphenol, has demonstrated multiple mechanisms through which it exerts antidiabetic activity, including inhibition of alpha-glucosidase and the glucose-elevating liver enzyme glucose-6-phosphatase, oxidative stress modulation, insulin sensitization, and AMPK activation (Bassoli 2008; Ishikawa 2007; Rodriguez de Sotillo 2006; Simsek 2015; Henry-Vitrac 2010; Andrade-Cetto 2010). Chlorogenic acid also lowers levels of blood lipids (Meng, Cao 2013). Chlorogenic acid’s inhibition of alpha-glucosidase allows it to delay glucose absorption, which can result in a more gradual rise in postprandial glucose levels (Johnston 2003).

In a clinical trial in 42 individuals with type 2 diabetes, 300 mg of a chlorogenic acid-containing plant extract daily for four weeks significantly reduced fasting plasma glucose, C-reactive protein (CRP), and liver enzymes compared with placebo (Abidov 2006). In another trial, a single dose of coffee polyphenols during a glucose-loading test in healthy individuals significantly protected endothelial function (Ochiai 2014). In a mouse study, green coffee bean extract, a rich source of chlorogenic acid, significantly reduced visceral fat accumulation and improved insulin sensitivity, effects that may have been due to suppression of genes associated with fat deposition and inflammation (Song 2014).

Raw green coffee beans are rich in chlorogenic acid (Farah 2008). However, the conventional coffee roasting process appears to significantly reduce the chlorogenic acid content of brewed coffee (Moon 2009; Zapp 2013).

Brown seaweed extract

Metabolic syndrome prevalence is lower in some Asian countries than in other parts of the world, and some researchers suspect dietary brown seaweed may be protecting these populations (Teas 2009). In laboratory experiments, brown seaweed extracts from Ascophyllum nodosum and Fucus vesiculosus inhibited alpha-glucosidase and alpha amylase enzymes (Roy 2011).

In a randomized controlled trial in 23 healthy subjects, a single 500-mg dose of brown seaweed extract caused a 48.3% decrease in post-meal blood sugar spikes. Significant reductions in post-meal insulin concentrations and improved insulin sensitivity were also observed (Paradis 2011).

(B) Alpha-amylase inhibition

Like alpha-glucosidase, alpha-amylase is an enzyme that breaks down larger sugars and starches into smaller molecules that can be rapidly absorbed. Inhibition of alpha-amylase is another way to reduce the rate of sugar absorption (Tundis 2010).

Sorghum extract

Grain sorghum (Sorghum bicolor) is cultivated for animal and human consumption in several parts of the world, especially Africa, Asia, and Latin America. The grain’s unique protein and starch composition reduce its digestibility and cause it to slow glucose absorption (Poquette 2014). Also, in animal models of diabetes, sorghum inhibited glucose production in the liver (gluconeogenesis) and improved insulin sensitivity. In a laboratory experiment, a flavonoid- and proanthocyanidin-rich sorghum extract inhibited the alpha-amylase enzymes that convert starch into sugars. In a randomized trial in 10 healthy men, muffins made with sorghum were shown to reduce average after-meal glucose and insulin responses (Hargrove 2011; Poquette 2014; Kim 2012; Park 2012).

(C) Additional mechanisms

Some natural products suppress postprandial hyperglycemia via other mechanisms, including inhibition of glucose transporters or sucrase, an enzyme that facilitates digestion and absorption of sucrose (table sugar).

Phloridzin

Phloridzin is a unique polyphenol found in high concentrations in apples and apple trees. This compound appears to suppress glucose absorption in the intestine by inhibiting sugar transporter systems in the intestine (SGLT1) and kidney (SGLT2). As a result, glucose reabsorption in the kidney is reduced and glucose excretion into the urine is promoted.

L-arabinose

L-arabinose is a poorly-absorbed five-carbon sugar found in the cell walls of many plants. L-arabinose inhibits the activity of sucrase, which is an intestinal enzyme that breaks down sucrose (table sugar) into the absorbable sugars glucose and fructose. When l-arabinose is consumed in combination with sucrose, the breakdown of sucrose is delayed, so that glucose is absorbed more slowly, which results in less exaggerated blood glucose and insulin responses. L-arabinose in combination with chromium, a natural insulin sensitizer, significantly lowered circulating glucose and insulin levels in nondiabetic subjects who underwent an oral sucrose challenge (Karley 2005; Kaats 2011; Krog-Mikkelsen 2011).

(D) Insulin Sensitizers

Chromium

Chromium, a trace mineral, is essential for carbohydrate and fat metabolism, and is believed to act as an insulin-sensitizing agent. Chromium deficiency has been associated with insulin resistance and diabetes (Suksomboon 2014; Anderson 1997). A 2014 study found chromium deficiency was common in people with prediabetes. The authors recommended screening for chromium deficiency in both prediabetics and diabetics, and supplementing if a deficiency was identified (Rafiei 2014).

Evidence suggests chromium supplementation may improve control of blood glucose, raise HDL cholesterol, and lower triglycerides in type 2 diabetes. Chromium has also been shown to significantly lower HbA1C in type 2 diabetics (Suksomboon 2014; Rabinovitz 2004).

Cinnamon

The culinary spice cinnamon has been shown to promote healthy glucose metabolism and improve insulin sensitivity (Anderson 2013; Couturier 2010; Sartorius 2014; Ranasinghe 2012). In a study in type 2 diabetics, a water-soluble cinnamon extract given at a dosage of 360 mg daily lowered HbA1C from 8.9% to 8.0%. The antidiabetic effects of cinnamon extracts have been attributed in part to activation of peroxisome proliferator-activated receptors, key regulators of glucose and fat metabolism (Sheng 2008; Lu 2012; Ferre’ 2004).

Several polyphenol compounds in cinnamon have free-radical-scavenging properties. In a rodent study, a specific cinnamon polyphenol, procyanidin B2, was shown to delay the formation of advanced glycation end products (AGEs) and diabetic cataracts (Muthenna 2013; Jayaprakasha 2006).

Omega-3 fatty acids

Omega-3 fats are healthy fats found in fish and some nuts, seeds, vegetables, and algae (Higdon 2014). Diets rich in omega-3 fatty acids have been shown to promote weight loss, enhance insulin sensitivity, and reduce death from cardiovascular disease by reducing inflammation, improving lipid profiles, and reducing blood clotting. When omega-3 fats are incorporated into cell membranes, they make the cell surface more fluid and pliable and appear to enhance cells’ ability to remove glucose from the bloodstream (McEwen 2010; Udupa 2013; Albert 2014; Franekova 2015). A large study in older adults demonstrated individuals with the highest blood concentrations of omega-3 fats, compared with the lowest, had up to 43% lower risk of diabetes (Djousse 2011).

In a randomized controlled trial in overweight type 2 diabetic patients, supplementation with the omega-3 fatty acid eicosapentaenoic acid (EPA) significantly decreased serum insulin, fasting glucose, HbA1C, and insulin resistance (Sarbolouki 2013). Another trial of supplementation with 2.3 g of the omega-3 fats EPA and docosahexaenoic acid (DHA) in 84 subjects with type 2 diabetes found a significant reduction in serum inflammatory biomarkers (Malekshahi Moghadam 2012). An eight-week trial in individuals with metabolic syndrome or early type 2 diabetes found fish oil lowered triglycerides and HbA1C and raised HDL cholesterol (Lee, Ivester 2014). Another trial in 44 type 2 diabetics found omega-3 supplementation for 10 weeks improved insulin sensitivity (Farsi 2014).

Magnesium

Magnesium is involved in more than 300 metabolic reactions and plays a key role in carbohydrate metabolism. Magnesium participates in insulin secretion and function, and low magnesium levels are correlated with insulin resistance (Gums 2004; Bertinato 2015; Paolisso 1990). Low magnesium levels are significantly more common in people with diabetes and impaired glucose tolerance compared with the general population, and higher magnesium levels correlate with lower HbA1C (Hata 2013; Hruby 2014; Hyassat 2014; Galli-Tsinopoulou 2014; Azad 2014). Higher magnesium intake is associated with decreased risk of developing type 2 diabetes (Guerrero-Romero 2014).

Magnesium supplementation has been shown to lower blood levels of glucose and lipids, as well as blood pressure, in type 2 diabetics. Magnesium supplements were also found to lower highly-sensitive C-reactive protein (hs-CRP), a marker of inflammation, in prediabetics with low serum magnesium (Solati 2014; Simental-Mendia 2014).

 

Oxidative Stress Inhibitors and Anti-Inflammatory Agents

Coenzyme Q10

Coenzyme Q10 (CoQ10) is essential to mitochondrial energy metabolism, and a powerful inhibitor of oxidative stress (Littarru 2007). CoQ10 deficiency has been associated with diabetes (Amin 2014; Kolahdouz 2013; Eriksson 1999). In a randomized controlled trial in 64 type 2 diabetic patients, supplementation with 200 mg CoQ10 per day for 12 weeks decreased serum HbA1C concentration and lowered levels of total and LDL cholesterol (Kolahdouz 2013). A clinical trial in 74 type 2 diabetic subjects found 100 mg CoQ10 twice daily resulted in significantly decreased HbA1C and blood pressure (Hodgson 2002). In a placebo-controlled trial in 23 statin-treated type 2 diabetics, 200 mg CoQ10 per day significantly improved a marker of vascular endothelial dysfunction (Hamilton 2009; Watts 2002).

In an animal model of diabetes, CoQ10 treatment significantly improved insulin resistance, reduced serum levels of insulin and glucose, and increased levels of the energy-regulating hormone adiponectin six-fold (Amin 2014). High levels of adiponectin have been linked to decreased risk of diabetes and cardiovascular complications (Lindberg 2015; Zoico 2004; Yamamoto 2014).

Long-term use of CoQ10 was demonstrated in two animal studies to be protective against progressive diabetic neuropathy. The beneficial effects of CoQ10 may have been attributable to reduction of oxidative damage and inflammation, both key factors implicated in diabetic neuropathy (Zhang, Eber 2013; Shi 2013).

Curcumin

Curcumin is a major active component of turmeric, the spice derived from the plant Curcuma longa. Turmeric has been used as a treatment for diabetes in Ayurvedic and traditional Chinese medicine for centuries. Curcumin’s primary mechanisms of action are its ability to neutralize reactive free radicals and reduce inflammation (Nabavi 2015; Zhang, Fu 2013; Meng, Li 2013).

A randomized controlled trial in 240 prediabetic subjects showed curcumin supplementation significantly lowered risk of progressing from prediabetes to type 2 diabetes. During the nine-month trial, none of the prediabetic subjects treated with curcumin progressed to diabetes, whereas over 16% of subjects in the control group were diagnosed with type 2 diabetes. By the end of the study, subjects in the curcumin group had significantly greater insulin sensitivity and beta-cell function, as well as higher adiponectin levels than the placebo group (Chuengsamarn 2012).

Additional experimental studies and human trials indicate curcumin is a promising natural agent for the prevention and treatment of diabetes and its complications. Curcumin appears to increase insulin sensitivity and reduce blood levels of glucose and lipids. It also may protect insulin-producing beta cells in the pancreas (Nabavi 2015; Zhang, Fu 2013).

Most curcumin formulations have relatively poor bioavailability, requiring high doses to achieve desired blood levels. Fortunately, a novel curcumin formulation, BCM-95, has been developed that delivers up to seven times more bioactive curcumin to the blood than earlier curcumin products (Antony 2008).

Resveratrol 

Resveratrol, a polyphenol that has received widespread attention for its anti-aging effects, holds promise in type 2 diabetes (Hausenblas 2015; Bruckbauer 2013; Fiori 2013; Tome’-Carneiro 2013; Mozafari 2015). A rigorous review of randomized controlled trials found resveratrol improved systolic blood pressure, HbA1C, and creatinine when used as an adjunct to drug treatment in type 2 diabetes (Hausenblas 2015). In one of these studies, supplementation with resveratrol at 1 g per day for 45 days resulted in a significant decrease in fasting glucose, insulin, and HbA1C and an increase in insulin sensitivity and HDL cholesterol levels. Notably, the improvements in HbA1C and HDL cholesterol were comparable to those achieved by leading antidiabetic drugs (Movahed 2013).

Lipoic acid

Lipoic acid is a free radical scavenger made by the body in small quantities, though levels decline significantly with age (Park, Karuna 2014; Higdon 2012). Lipoic acid may support healthy blood glucose control by activating AMPK, protecting pancreatic beta cells, and augmenting glucose removal from the bloodstream. Lipoic acid has been used for the prevention and treatment of diabetic neuropathy in Germany for several decades (Ziegler 1999; Gomes 2014; Golbidi 2011; Ibrahimpasic 2013).

In a study in subjects with impaired glucose tolerance, arterial flow (a measure of endothelial function) was markedly decreased during fasting and after a glucose challenge. Intravenous administration of 300 mg lipoic acid before the glucose challenge prevented the endothelial dysfunction induced by high blood glucose. Lipoic acid decreases oxygen free radicals, which in excess promote endothelial dysfunction and contribute to diabetes, high blood pressure, and cardiovascular disease (Xiang 2008; Park, Karuna 2014; Gomes 2014).

Lipoic acid comes in two “mirror image” forms labeled “R” and “S.” The R form is the active form produced and used in living systems (Gomes 2014). Inexpensive chemical manufacturing produces equal quantities of R and S lipoic acid, often labeled “R/S lipoic acid” or simply “alpha-lipoic acid” (Flora 2009). Newer precision techniques allow production of a pure, more stable R-lipoic acid supplement, delivering the most bioavailable form. This form is known as sodium R-lipoate, or Na-RALA.  A dose of pure R-lipoic acid provides twice the active ingredient compared with typical alpha-lipoic acid supplements.

Blueberry extract

Blueberries are a concentrated source of polyphenols and anthocyanins that have multiple antidiabetic effects, including protection of pancreatic beta cells, anti-inflammatory properties, and free-radical-scavenging abilities (Liu, Gao 2015; Martineau 2006; Abidov 2006).

A four-week randomized controlled trial of blueberry supplementation was conducted in 32 obese, insulin-resistant adults without diabetes. Subjects were given 45 g of freeze-dried blueberry powder—the equivalent of two cups of whole blueberries—daily for six weeks. Compared with placebo, blueberry treatment significantly improved insulin sensitivity (Stull 2010).

In a study in rodents fed a high-fructose diet, fasting insulin was elevated, and insulin sensitivity and pancreatic beta-cell function declined. However, when the diet was supplemented with blueberries, these changes were minimized; and when a larger percentage of the diet was derived from blueberries, the effect was greater. Cholesterol and abdominal fat also decreased in the blueberry-fed animals (Khanal 2012).

Grape polyphenols

Grapes are a source of polyphenols, proanthocyanidins, and resveratrol, all of which modulate oxidative stress and have been studied in a wide range of health conditions, including high blood pressure, cancer, and Alzheimer disease (Pasinetti 2014; Kaur 2009; Feringa 2011). Grape polyphenols appear to have important antidiabetic effects and protect tissues from the damaging effects of blood sugar elevations.

In a four-week, randomized, placebo-controlled trial in 32 type 2 diabetics, consumption of 600 mg per day of grape seed extract significantly lowered fructosamine compared with placebo. Fructosamine is a test similar to HbA1C that measures blood sugar level over several weeks. Grape seed extract also lowered total cholesterol and hs-CRP, and significantly elevated blood glutathione, one of the body’s primary internal antioxidants (Kar 2009). Another trial found the non-alcoholic portion of red wine, which is rich in grape polyphenols, increased insulin sensitivity and reduced cardiovascular risk (Chiva-Blanch 2013).

Gamma tocopherol

After-meal blood sugar surges can injure the lining of blood vessels, causing endothelial dysfunction and vascular disease. Gamma tocopherol is a form of vitamin E with both anti-inflammatory and free-radical-scavenging activity. Two trials in healthy men found gamma tocopherol supplementation protected against changes associated with endothelial dysfunction induced by after-meal glucose spikes (Mah, Noh 2013; Masterjohn 2012; Mah, Pei 2013).

Additional Support

Vitamin D

Vitamin D deficiency has been associated with both diabetes and obesity, and evidence suggests vitamin D status is closely related to glucose metabolism. People with low vitamin D were more likely to have diabetes, independent of their body weight (Clemente-Postigo 2015).

Several mechanisms have been suggested to account for the association between vitamin D levels and poor blood glucose control. Through its role in calcium regulation, vitamin D may improve insulin sensitivity and regulate pancreatic beta cell function. Vitamin D may also modulate systemic inflammation, which is associated with insulin resistance and type 2 diabetes. Finally, vitamin D may directly stimulate production of insulin receptors in target tissues and thus enhance glucose clearance from the blood (Clemente-Postigo 2015; Pittas 2007). An optimal target range for vitamin D blood levels is between 50 and 80 ng/mL.

Folate

In type 2 diabetes, elevated plasma homocysteine is strongly linked to increased risk of cardiovascular disease and death. Homocysteine promotes endothelial dysfunction through a number of different mechanisms. The B vitamin folate, in concert with vitamin B12, lowers homocysteine by converting it back to the amino acid methionine. Both low folate intake and low blood folate levels are strongly associated with high plasma homocysteine (Selhub 2000; Moat 2004; Sudchada 2012; Van Guelpen 2009; Miller 2003; de Bree 2001; Koehler 2001).

A thorough review and analysis of randomized controlled trials assessed the effect of folic acid supplementation on homocysteine levels in type 2 diabetics. In this population, 5 mg per day of folic acid significantly decreased homocysteine levels, to a degree believed to lower the risk of cardiovascular disease, and improved glycemic control (Sudchada 2012).

Genetic predisposition to inefficient conversion of folic acid into the metabolically active 5-methyltetrahydrofolate (5-MTHF) is common (Huo 2015). Supplementation with L-methylfolate (instead of folic acid) avoids this potential problem and is preferable to folic acid.

Irvingia gabonensis

Also known as African mango, Irvingia gabonensis is an African tree that bears mango-like fruit (MMSCC 2015). An extract of irvingia seed has been shown to lower blood glucose and lipid levels, and reduce excess body weight (Ross 2011; Ngondi 2009; Ngondi 2005). In a randomized controlled trial, 150 mg of a proprietary extract from Irvingia gabonensis, taken twice daily for 10 weeks, significantly decreased body weight, body fat, and waist circumference in overweight subjects. There were also improvements in several metabolic parameters related to insulin resistance, including increased adiponectin and decreased leptin and CRP (Ngondi 2009).

In another trial, a combination of extracts from irvingia and Cissus quadrangularis, a West African vine, produced significantly larger reductions in body weight and fat, total cholesterol, LDL cholesterol, and fasting blood glucose compared with the Cissus extract alone (Oben, Ngondi, Momo 2008).

Nicotinamide riboside 

Nicotinamide adenine dinucleotide (NAD+) is a critical regulator of cellular energy (Kim, Oh 2015). It is also a cofactor for sirtuin proteins, which are involved in many metabolic activities and associated with longevity. Aging is associated with declining activity of SIRT1, the gene that encodes the sirtuin 1 protein, and preclinical studies have shown increasing SIRT1 expression prolongs lifespan (Poulose 2015). Age-related decline of NAD+ levels has been associated with a reduction in SIRT1 activity (Braidy 2011; Gomes 2013). NAD+ metabolism is also implicated in the causation and complications of diabetes (Yoshino 2011; Canto 2015; Imai 2009).

Supplementation with nicotinamide riboside, an NAD+ precursor, boosts cellular NAD+ levels (Bogan 2008; Khan 2014). Animal research has shown nicotinamide riboside can improve insulin sensitivity, augment the benefits of exercise, combat neurodegeneration, and mitigate the negative effects of a high-fat diet (Chi 2013; Canto 2012). In an animal model of type 2 diabetes, nicotinamide riboside supplementation reduced liver inflammation and improved glucose control (Lee, Hong 2015).

 

 

 

SUGGESTED SUPPLEMENTATION

Under no circumstances should people suddenly stop taking diabetic drugs, especially insulin. A type 1 diabetic will never be able to stop taking insulin. However, it is possible to improve glucose metabolism, control, and tolerance with the following supplements:

Primary Suggestions

  • Support Healthy Glucose Metabolism:
    • Sorghum bran extract
    • White mulberry leaf extract
    • Phloridzin (from apple extract [root bark])
  • Supports Healthy After-Meal Glucose Levels:
    • Green Coffee Bean Extract
  • Support Healthy Glucose Absorption:
    • Chromium
    • Cinnamon extract (bark)
    • Seaweed extracts
  • Protect against Damaging Glycation:
    • Benfotiamine
    • Carnosine
    • Pyridoxal-5’-phosphate

 

Additional Support

  • Bilberry extract (std. to 36% total anthocyanins [36 mg]): 100 mg daily
  • Black tea extract (std. to 25% theaflavins [87.5 mg]): 350 mg daily
  • Blueberry extract: 375 – 1500 mg daily
  • Coenzyme Q10 (CoQ10) (as ubiquinol): 50 – 200 mg daily
  • Curcumin (as enhanced absorption BCM-95): 400 – 630 mg daily
  • Fish oil (with olive polyphenols and sesame lignans): 1400 mg EPA and 1000 mg DHA daily
  • Folate (as L-methylfolate): 1000 – 5000 mcg daily
  • Grape extract: providing 150 – 600 mg proanthocyanidins daily
  • L-arabinose: 475 - 950 mg daily
  • Green tea extract (std. to 98% polyphenols): 725 – 1500 mg daily
  • Gynostemma pentaphyllum extract: 450 mg daily preferably in divided doses
  • Irvingia gabonensis: 300 mg daily
  • L-carnitine: 500 – 2000 mg daily
  • Magnesium: 500 – 1500 mg daily
  • Nicotinamide riboside: 100 mg daily
  • Resveratrol: 250 mg daily
  • R-lipoic acid: 240 – 480 mg daily
  • Rose hip extract (std. to 5% trans-tiliroside [18.6 mg]): 1119 mg daily preferably in divided doses
  • Vitamin B12 (as methylcobalamin): 1 – 8 mg daily, sometimes up to 40 mg daily (People who take metformin should supplement with B12 because metformin can cause B12 deficiency.)
  • Vitamin D: 5000 – 8000 IU daily, depending upon blood levels of 25-OH-vitamin D
  • Vitamin E: 400 mg daily with at least 200 mg gamma tocopherol

 

 

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