Diabetes & Glucose Control
Emerging Strategies | Life Extension
The consequences of uncontrolled diabetes are severe blindness, kidney failure, increased risk of heart disease, and painful peripheral nerve damage. Today, most practitioners focus treatment on strict blood sugar control. While diabetes is characterised by excess blood glucose (the form of sugar used by cells as energy), this simplified approach can actually hasten the progression of the most common form of diabetes and does nothing to address the damage it causes.
A new approach to diabetes recognition and treatment is needed because the conventional wisdom has failed us. America is in the midst of a diabetes epidemic. 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 the epidemic of heart disease, as well as being a leading cause of amputation and blindness among adults.
It is crucial that diabetics (and those predisposed to diabetes) understand the ways in which blood glucose causes damage and take active steps to interrupt these processes. The most notorious process is glycation (i.e., sugar molecules reacting with proteins to produce nonfunctional 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).
Oxidation stress is also central to the damage caused by diabetes. Diabetics suffer from high levels of free radicals that damage arteries throughout the body. It is important that diabetics understand the need for antioxidant therapy to help reduce oxidation stress and lower the risk of diabetic complications.
Diabetes & Glucose Control
The Difference Between Type 1 & Type 2 Diabetes
There are two types of diabetes: type 1 and type 2. Underlying both forms of diabetes is a disorder of insulin production, use, or both. 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.
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 (called beta-cells or β-cells) that make insulin. Type 1 diabetes accounts for about 5 to 10 percent 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 that goes through identifiable stages. In the early stages, both insulin and glucose levels are elevated (conditions called hyperinsulinemia and hyperglycemia, respectively). In the later stages, insulin levels are reduced, and blood glucose levels are very elevated. Although few people are aware of this crucial distinction, therapy for type 2 diabetes should be tailored to the stage of the disease.
Risk factors for type 2 diabetes include 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.
Diabetes & Glucose Control
The Diabetes Damage Cascade
Glycation and oxidative stress are central to the damage caused by diabetes. Unfortunately, neither of them figures into conventional treatment for diabetes, which is generally concerned only with blood sugar control.
Glycation occurs when glucose reacts with protein, resulting in sugar-damaged proteins called advanced glycation end products (AGEs) (Kohn 1984; Monnier 1984). One well-known AGE among diabetics is glycated hemoglobin (HbA1c). HbA1c is created when glucose molecules bind to hemoglobin in the blood. Measuring HbA1c in the blood can help determine the overall exposure of hemoglobin to glucose, which yields a picture of long-term blood glucose control.
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 percent reduction in HbA1c correlated with a 21 percent reduction in risk for any complication of diabetes, a 21 percent reduction in deaths related to diabetes, a 14 percent reduction in heart attack, and a 37 percent reduction in microvascular complications (Stratton 2000).
High levels of blood glucose and glaciation 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. Oxidation stress in diabetes is also linked to endothelial dysfunction, the process that characterises 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.
Diabetes & Glucose Control
Symptoms And Diagnosis Of Diabetes
Common symptoms of diabetes include increased thirst and urination, unusual weight changes, irritability, fatigue, and blurry vision. Clinical abnormalities include hyperglycemia and glucose in the urine. The breath might smell sweet because of ketones in the blood (ketosis), which are naturally sweet smelling. Dark outgrowths of skin (skin tags) may also appear.
The most common clinical tests used to diagnose diabetes are measures of blood glucose. The fasting plasma glucose (FPG) test measures the amount of glucose in the blood after fasting. Prediabetes is diagnosed if the fasting blood glucose level is between 100 and 125 mg/dL. Diabetes is diagnosed if the fasting blood glucose level rises to 126 mg/dL or above.
The oral glucose tolerance test (OGTT) is used to measure insulin response to high glucose levels. During this test, patients are given glucose, and the rise in blood glucose levels is measured. Prediabetes is diagnosed if the glucose level rises to between 140 and 199 mg/dL. Diabetes is diagnosed if blood glucose levels rise to 200 mg/dL or higher.
The HbA1c test is also helpful in diagnosing less severe cases of diabetes. From this test, clinicians can estimate the average blood glucose level during the preceding two to four months. Normally 4 to 6 percent of hemoglobin is glycosylated, which corresponds to average blood glucose between 60 and 120 mg/dL. Mild hyperglycemia increases HbA1c to 8 to 10 percent (or 180 to 240 mg/dL), while severe hyperglycemia increases HbA1c values up to 20 percent. For diabetics, a healthy HbA1c level is less than 7 percent, which corresponds to an average blood glucose level of 150 mg/dL or less.
Diabetes & Glucose Control
The Truth About Type 2 Diabetes Therapy
Before discussing therapy for type 2 diabetes, it is important to understand the logic behind conventional therapy and to understand why this logic is flawed. 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 assumption defies common sense.
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 copious amounts of insulin to normalize glucose levels. This short-term, biological fix successfully drives glucose into cells, thereby lowering blood glucose levels, but it also hastens the progression of the disease. 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. Insulin levels drop far below normal, allowing blood glucose to rise even higher and inflict greater damage.
Unfortunately, many early-stage diabetics are prescribed drugs (e.g., sulfonylureas) designed to boost insulin levels. Considering that insulin levels are already high, this strategy is counterproductive and may actually serve to hasten the disease by further exhausting the insulin receptors on cell membranes. 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). There is also evidence that increased levels of insulin contribute to the proliferation of colorectal cells, which suggests that high levels of insulin may be a factor in the development of colorectal cancer (Tran 2006).
A Program For Early Diabetics
There are acute differences between early and advanced stages of diabetes. Thus, it doesn’t make sense to treat all people with type 2 diabetes the same. In the early stages of the disease, people suffer from both hyperglycemia and hyperinsulinemia. Rather than take drugs that further increase the level of insulin in the blood, people with type 2 diabetes would do better to pursue therapies that increase the sensitivity of insulin receptors on the cell membranes.
One of the best defenses against mild to moderate type 2 diabetes and hyperinsulinemia 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). One study also showed that while some medications delay the development of diabetes, diet and exercise work better. Just 30 minutes a day of moderate physical activity, coupled with a 5 to 10 percent reduction in body weight, produces a 58 percent reduction in the incidence of diabetes among people at risk (Sheard 2003). The American Diabetes Association recommends a diet high in fiber, unrefined carbohydrates, and low in saturated fat (Sheard 2004). Foods with a low glycemic index are especially recommended because they blunt the insulin response. For more information on glycemic index, see the Obesity protocol.
The high-carbohydrate, high-plant-fiber (HCF) diet popularized by James Anderson, MD, has substantial support and validation in the scientific literature as the diet of choice in the treatment of diabetes (Anderson 2004; Hodge 2004). The HCF diet is high in cereal grains, legumes, root vegetables, and restricts simple sugar and fat intake. The diet consists of 50 to 55 percent complex carbohydrates, 12 to 16 percent protein, and less than 30 percent fat, mostly unsaturated. The total fiber content is between 25 and 50 grams daily. The HCF diet produces many positive metabolic effects, including the following: lowered post-meal hyperglycemia and delayed hypoglycemia, increased tissue sensitivity to insulin, reduced low-density lipoprotein (LDL) cholesterol and triglyceride levels, increased high-density lipoprotein (HDL) cholesterol levels, and progressive weight loss.
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 antidiabetic 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. A benchmark assessment of kidney function, followed by an annual renal evaluation, is essential. 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. Also, metformin should not be used for two days before or after having an x-ray procedure with an injectable contrast agent because of the rare risk of lactic acidosis.
Metformin is effective on its own, but it may also be prescribed in combination with another class of insulin sensitizers called thiazolidinediones (TZDs; e.g., pioglitazone or Actos®, and rosiglitazone or Avandia®). TZDs increase insulin sensitivity and stimulate release of insulin from β-cells in the pancreas. TZD treatment also improves blood pressure and relieves vascular and lipid defects (Meriden 2004). However, TZDs have potentially serious side effects, including liver toxicity, which requires regular monitoring of liver function (Isley 2003; Marcy 2004).
In addition to these two prescription drugs, many 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 drugs can reverse mild to moderate hyperglycemia before stronger drugs are needed and permanent damage is done.
Drug Therapy For Advanced Diabetics
Some people, however, will not have the benefit of this knowledge before their type 2 diabetes advances to a more dangerous stage. In severe hyperglycemia, the pancreas becomes burned out after producing high levels of insulin for a long time. Insulin levels drop as a result of decreased production, and blood glucose levels are allowed to rise to very high, toxic levels. Although diet and exercise, along with supplementation, are still strongly recommended, prescription drugs might also be necessary.
Sulfonylurea drugs stimulate pancreatic secretion of insulin. Unfortunately, they are often prescribed as first-line treatment for mild to moderate type 2 diabetics, even when their use is inappropriate. By increasing levels of insulin, which are already raised, sulfonylurea drugs actually hasten the progression of early type 2 diabetes by exhausting insulin receptors faster, which causes the pancreas to burn out more quickly. Sulfonylurea drugs should really be considered a “last resort” for people with severe hyperglycemia.
Insulin replacement therapy is also a last resort for type 2 diabetics. While insulin therapy is universal and essential among type 1 diabetics, it is reserved for severe, refractory (nonresponsive to treatment) type 2 diabetics only. Proper dosing and monitoring of blood glucose are essential as too much insulin causes low blood sugar and coma, and too little insulin creates hyperglycemia. A new delivery system for insulin was recently approved by the US Food and Drug Administration. This new system allows for inhaled insulin.
What You Have Learned So Far
- 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.
- Type 1 diabetes is caused by an autoimmune reaction that destroys insulin-producing β-cells in the pancreas. Type 2 diabetes is caused by decreased insulin sensitivity.
- Type 2 diabetes has reached epidemic proportions in America. The incidence of this disease, which is caused by obesity and genetic predisposition, has increased dramatically over the past five years. It is more common among older people than in other segments of the population, although it is also affecting children at increasing rates.
- People with mild to moderate type 2 diabetes should avoid drugs and therapies that increase levels of insulin. Their disease is characterized by elevated levels of both insulin and glucose. Instead, therapy should focus on strategies to increase insulin sensitivity.
- Possible complications in diabetes arise from damage to enzymes and other proteins that impair their function and from resulting damage to blood vessels. The subsequent decreased blood flow, increased vulnerability to oxidant stress, and decreased antioxidant capacity all interact to produce end-organ damage to the eyes, nerve tissue, kidneys, and cardiovascular system.
- Type 1 diabetics always require insulin therapy to replace their lost insulin.
Diabetes & Glucose Control
Nutritional Supplementation For Diabetics
Type 1 diabetics will need to be on insulin therapy for life, although the supplements mentioned in this section may help offset some of the complications caused by diabetes (e.g., reduced antioxidant capacity and glycation) as well enhance glucose metabolism. Type 2 diabetics can counteract the progression of their disease by improving insulin sensitivity, enhancing glucose metabolism, and attempting to mitigate the complications of diabetes. The following supplements have been shown to improve blood sugar control or limit diabetic damage:
Lipoic acid. As a powerful antioxidant, lipoic acid positively affects important aspects of diabetes, including blood sugar control and the development of long-term complications such as disease of the heart, kidneys, and small blood vessels (Jacob 1995, 1999; Kawabata 1994; Melhem 2002; Nagamatsu 1995; Song 2005; Suzuki 1992).
Lipoic acid plays a role in preventing diabetes by reducing fat accumulation. In animal studies, lipoic acid reduced body weight, protected pancreatic β-cells from destruction, and reduced triglyceride accumulation in skeletal muscle and pancreatic islets (Doggrell 2004; Song 2005).
Lipoic acid has been approved for the prevention and treatment of diabetic neuropathy in Germany for nearly 30 years. Intravenous and oral lipoic acid reduces symptoms of diabetic peripheral neuropathy (Ametov 2003). Animal studies have suggested that lipoic acid is more effective when taken with gamma-linolenic acid (GLA) (Cameron 1998; Hounsom 1998).
Diabetes also damages deep nerves that control vital organs, such as the heart and digestive tract. In a large clinical trial, diabetics (with symptoms caused by nerve damage affecting the heart) showed significant improvement without significant side effects from 800 mg oral lipoic acid daily (Ziegler 1997a,b).
Biotin. Biotin enhances insulin sensitivity and increases the activity of glucokinase, the enzyme responsible for the first step in the utilization of glucose by the liver. Glucokinase concentrations in diabetics are very low. Animal studies have shown that a high biotin diet can improve glucose tolerance and enhance insulin secretion (Zhang 1996; Furukawa 1999).
Carnitine. An extensive body of literature supports the use of carnitine in diabetes (Mingrone 2004). Carnitine lowers blood glucose and HbA1c levels, increases insulin sensitivity and glucose storage, and optimizes fat and carbohydrate metabolism. Carnitine deficiency is common in type 2 diabetes. In a large human trial, acetyl-L-carnitine helped prevent or slow cardiac autonomic neuropathy in people with diabetes (Turpeinen 2005).
Carnosine. Carnosine is a glycation inhibitor that has been shown to exhibit protective effects against diabetic nephropathy and reduce the formation of AGEs (Janssen 2005; Yan 2005).
Studies show that diabetics’ cells have lower-than-normal carnosine levels, similar to levels in older adults (McFarland 1994). Carnosine lowers elevated blood sugar levels, limits oxidant stress and elevated inflammation, and prevents protein cross-linking in diabetics and otherwise healthy aging adults (Jakus 2003; Hipkiss 2005; Nagai 2003; Hipkiss 2001; Aldini 2005). Additionally, carnosine works ‘behind the scenes’ to offer the following protection (for diabetics) against the physiological destruction caused by high blood sugar:
- Carnosine reduces oxidation and glycation of low-density lipoprotein (LDL), which helps decrease the incidence of diabetes-induced atherosclerosis (Lee 2005; Rashid 2007).
- Carnosine reduces protein cross-linking in the lens of the eye and helps to reduce the risk of cataract (a common diabetic complication) (Yan 2005; Yan 2008).
- Carnosine supplementation also prevents the microscopic blood vessel damage that produces diabetic retinopathy, a major cause of blindness in diabetics (Pfister 2011).
- Carnosine supplements prevent loss of sensory nerve function (neuropathy) in diabetic animals (Kamei 2008).
Chromium. Chromium is an essential trace mineral that plays a significant role in sugar metabolism. Chromium supplementation helps control blood sugar levels in type 2 diabetes and improves metabolism of carbohydrates, proteins, and lipids. Several studies have shown encouraging results from chromium supplementation:
- A controlled human study of type 2 diabetics compared two forms of chromium (brewer’s yeast and chromium chloride) (Bahijiri 2000). Both forms of chromium significantly improved blood sugar control. Positive results were also seen in two smaller human trials (Ghosh 2002; Jovanovic 1999).
- A large human trial compared the effects of 1000 mcg chromium, 200 mcg chromium, and placebo (Anderson 1997). HbA1c values improved significantly in the group receiving 1000 mcg after two months and in both chromium groups after four months. Fasting glucose was also lower in the group taking the higher dose of chromium. Chromium is a highly reactive metal ion, requiring balance through additional organic materials in order to stabilize and enhance its effects.Amla(Indian gooseberry) and shilajit have more recently been shown to synergistically enhance chromium’s beneficial action. In a randomized clinical trial of 150 individuals with type 2 diabetes, 200 mcg twice per day of this novel chromium compound in addition to standard medication induced a greater reduction in fasting blood glucose than placebo (6%on average) and lowered postprandial blood glucose (14.2%) after just two months (Bhattacharyya 2010).
Coenzyme Q10. Coenzyme Q10 (CoQ10) improves blood sugar control, lowers blood pressure, and prevents oxidative damage caused by disease. In a controlled human trial, type 2 diabetics given 100 mg CoQ10 twice daily experienced improved glycemic control as measured by lower HbA1c levels and blood pressure (Hodgson 2002). In a separate study, CoQ10 improved blood flow in type 2 diabetics, an outcome attributed to CoQ10’s ability to lower vascular oxidative stress (Watts 2002). In a third study, improved blood flow correlated with decreased HbA1c (Playford 2003).
In animal studies, CoQ10 quenched free radicals, improved blood flow, lowered triglyceride levels, and raised HDL levels, suggesting a role for CoQ10 in preventing and managing complications of diabetes (Al-Thakafy 2004). Animal studies have also shown that CoQ10 levels are depleted by diabetes (Kucharska 2000).
Dehydroepiandrosterone. Recent studies have yielded very encouraging results supporting dehydroepiandrosterone (DHEA) supplementation in diabetics. DHEA has been shown to improve insulin sensitivity and obesity in human and animal models (Yamashita 2005). Although its mechanism of action is poorly understood, it is thought that DHEA improves glucose metabolism in the liver (Yamashita 2005).
Animal studies have also demonstrated that DHEA increases β-cells on the pancreas, which are responsible for producing insulin (Medina 2006).
In humans, DHEA levels are sensitive to elevated glucose; thus, higher glucose levels tend to be associated with decreased DHEA levels (Boudou 2006). One proposed mechanism of action in humans is linked to DHEA’s metabolism into testosterone. DHEA is an adrenal hormone that can be converted into either testosterone or estrogen. Studies have shown that testosterone improves insulin sensitivity in men, suggesting that DHEA’s conversion into testosterone may be responsible for its beneficial effects in improving insulin sensitivity (Kapoor 2005).
Essential fatty acids. In human experiments, omega-3 fatty acids lowered blood pressure and triglyceride levels, thereby relieving many of the complications associated with diabetes. In animals, omega-3 fatty acids cause less weight gain than other fats do; they have also been shown to have a neutral effect on LDL, while raising HDL and lowering triglycerides (Petersen 2002). There are two types of essential fatty acids:
- Omega-3. Marine oil contains omega-3 fatty acids. The research on omega-3 fatty acids stems from studies of the Inuit (Eskimo) people, who seldom suffer from heart attacks even though their diets contain an enormous amount of fat from fish, seals, and whales, presumably because these are very high in omega-3 fatty acids. Omega-3 fatty acids found in marine oil lower blood triglyceride levels, contribute to “thinning” blood, and decrease inflammation (Ebbesson 2005). These effects partially explain many of fish oil’s benefits.
- Omega-6. Diabetic neuropathy is a gradual degeneration of peripheral nerve tissue. There is some evidence that GLA, an omega-6 fatty acid, can be helpful if given long enough to work. In one double-blind, placebo-controlled study, 111 people with mild diabetic neuropathy received either 480 mg daily of GLA or placebo. After 12 months, the group taking GLA was doing significantly better than the placebo group in 13 out of 16 measures of nerve function, with patients whose diabetes was under control doing best (Keen 1993). There is also evidence that GLA is more effective for diabetic neuropathy when combined with lipoic acid (Hounsom 1998).
Fiber. Eating a diet rich in high-fiber foods prevents and reduces the harm caused by chronically elevated blood glucose.
One study reported the results of diabetic individuals consuming a diet supplying 25 grams of soluble fiber and 25 grams of insoluble fiber (about double the amount currently recommended by the American Diabetes Association). The fiber was derived from foodstuffs, with no emphasis placed on special or unusual fiber-fortified foods or fiber supplements. A high-fiber diet reduced blood glucose levels by an average of 10 percent (Chandalia 2000).
Fiber is also valuable because it produces a feeling of satiety, reducing the desire to overeat. Because high-fiber foods are digested more slowly than other foods, hunger pangs are forestalled. For the most part, fibrous foods are healthful (nutrient dense and low-fat).
Fiber should be added slowly, gradually replacing low-fiber foods, for the following reasons: (1) insulin and prescription drugs may have to be adjusted to accommodate lower blood glucose levels, and (2) without a gradual introduction of the new material, intestinal distress could occur, including bloating, flatulence, and cramps.
Some individuals prefer to bolster fiber volume by adding supplemental fiber in the form of pectin, gums, and mucilages to each meal. Calculate the amount of fiber gained from foodstuffs and supplement with enough to compensate for shortfalls. Monitor blood glucose levels closely to assess gains and adjust oral or injectable hypoglycemic agents.
Propolmannan. Specially processed, propolmannan is a polysaccharide fiber derived from a plant (Amorphophallus konjac) that grows only in the remote mountains of Northern Japan.
Used throughout Asia as a source of bulk in the diet, it creates a viscous barrier that impedes carbohydrate digestion, suppressing postprandial (after-meal) blood sugar surges. Propolmannan also slows “gastric emptying”—the passage of food from the stomach into the small intestine—impeding carbohydrate overexposure in the digestive tract. Propolmannan’s power to safely suppress postprandial glucose surges has generated compelling results. In a group of 72 diabetics given konjac foods, postprandial glucose levels fell by an average of 84.6% (Huang 1990).
In placebo-controlled human studies, those taking propolmannan before meals lost 5.5 to 7.92 pounds after eight weekswithout changing their diets. The placebo groups in these studies showed no significant weight loss. The propolmannan groups also showed reductions in blood lipid/glucose levels (Walsh 1984; Biancardi 1989).
Flavonoids. Flavonoids are antioxidants that help reduce damage associated with diabetes. In animal studies, quercetin, a potent flavonoid, decreased levels of blood glucose and oxidants. Quercetin also normalized levels of the antioxidants superoxide dismutase, vitamin C, and vitamin E. Quercetin is more effective at lower doses and ameliorates the diabetes-induced changes in oxidative stress (Mahesh 2004).
Magnesium. Diabetics are often deficient in magnesium, which is depleted by medications and the disease process (Eibl 1995; Elamin 1990; Tosiello 1996). One double-blind study suggested that magnesium supplementation enhanced blood sugar control (Rodriguez-Moran 2003).
N-acetylcysteine. N-acetylcysteine (NAC) is a powerful antioxidant that is used to treat acetaminophen overdose. Among diabetic rats, it has also demonstrated the ability to protect the heart against endothelial damage and oxidative stress that is associated with heart attacks among diabetics. In one study, NAC was able to increase the availability of nitric oxide in diabetic rats, thus improving their blood pressure as well as reducing the level of oxidative stress in their hearts (Xia 2006). In a human study examining the effects of broad-based antioxidants, NAC, in addition to vitamins C and E, was able to reduce oxidative stress after a moderate-fat meal (Neri 2005).
Silymarin. In animal studies, silymarin was shown to improve insulin levels among induced cases of diabetes (Soto 2004). A small, controlled clinical study evaluated type 2 diabetics with alcohol-induced liver failure (Velussi 1997). Those receiving 600 mg silymarin daily experienced a significant reduction in fasting blood and urine glucose levels. Fasting glucose levels rose slightly during the first month of supplementation but declined thereafter from an average of 190 mg/dL to 174 mg/dL. As daily glucose levels dropped (from an average of 202 mg/dL to 172 mg/dL), HbA1c also substantially decreased. Throughout the course of treatment, fasting insulin levels declined by almost one-half, and daily insulin requirements decreased by about 24 percent. Liver function improved. A lack of hypoglycemic episodes suggests silymarin lowered as well as stabilized blood glucose levels.
Vitamin B3. Vitamin B3 (niacin) is required for the proper function of more than 50 enzymes. Without it, the body is not able to release energy or make fats from carbohydrates. Vitamin B3 is also used to make sex hormones and other important chemical signal molecules.
In the past, the use of niacin was discouraged in diabetic individuals because it was found to increase insulin resistance and degrade glycemic control, particularly at high doses (Sancetta 1951). However, emerging clinical evidence shows that niacin is both safe and effective for diabetics (Meyers 2004).
There is evidence that niacin reduces the risk of developing type 1 diabetes (Pocoit 1993; Pozzilli 1993). Niacinamide helps restore β-cells, or at least slow their destruction. Because niacin can disrupt blood sugar control in diabetics, individuals taking any form of niacin, including inositol hexaniacinate, must closely monitor blood sugar levels and discontinue treatment in the event of worsening of diabetic control. Inositol hexaniacinate has long been used in Europe to lower cholesterol levels and improve blood flow in individuals with intermittent claudication.
Vitamin C. Several preclinical studies evaluated vitamin C’s role during mild oxidative stress. The aqueous humor of the eye provides surrounding tissues with a source of vitamin C. Since animal studies have shown that glucose inhibits vitamin C uptake, this protective mechanism may be impaired in diabetes (Corti 2004). Supplementation with antioxidant vitamins C and E plays an important role in improving eye health (Peponis 2004). High vitamin C intake depresses glycation, which has important implications for slowing diabetes progression and aging (Krone 2004).
Vitamin C, through its relationship to sorbitol, also helps prevent ocular complications in diabetes. Sorbitol, a sugar-like substance that tends to accumulate in the cells of people with diabetes, tends to reduce the antioxidant capacity of the eye, with a number of possible complications. Vitamin C appears to help reduce sorbitol buildup (Will 1996).
Vitamin C also has a role in reducing the risk of other diabetic complications. In one clinical study, vitamin C significantly increased blood flow and decreased inflammation in patients with both diabetes and coronary artery disease (Antoniades 2004). Three studies suggest that vitamin C, along with a combination of vitamins and minerals (Farvid 2004), reduces blood pressure in people with diabetes (Mullan 2002) and increases blood vessel elasticity and blood flow (Mullan 2004).
Vitamin E. Vitamin E has been shown to significantly reduce the risk of developing type 2 diabetes (Montonen 2004). One double-blind trial found a reduction in the risk of cardiac autonomic neuropathy, or damage to the nerves that supply the heart, which is a complication of diabetes (Manzella 2001). Additional evidence documented benefits for diabetic peripheral neuropathy (Tutuncu 1998), blood sugar control (Kahler 1993; Paolisso 1993a,b; Paolisso 1994), and cataract prevention (Paolisso 1993a,b; Paolisso 1994; Seddon 1994). In addition, vitamin E enhances sensitivity to insulin in type 2 diabetics (Paolisso 1993a,b).
Botanical Supplements For Diabetes
Before insulin, botanical medicines were used to treat diabetes. They are remarkably safe and effective. However, because many botanical medicines function similarly to insulin, people taking oral diabetes medications or insulin should use caution to avoid hypoglycemia. Botanical medicines should be integrated into a regimen of adequate exercise, healthy eating, nutritional supplements, and medical support.
Cinnamon. Cinnamon has been used for several thousand years in traditional Ayurvedic and Greco-European medical systems. Native to tropical southern India and Sri Lanka, the bark of this evergreen tree is used to manage conditions such as nausea, bloating, flatulence, and anorexia. It is also one of the world’s most common spices, used to flavor everything from oatmeal and apple cider to cappuccino. Recent research has revealed that regular use of cinnamon can also promote healthy glucose metabolism.
Astudy at the US Department of Agriculture’s Beltsville Human Nutrition Research Center isolated insulin-enhancing complexes in cinnamon that are involved in preventing or alleviating glucose intolerance and diabetes (Anderson 2004). Three water-soluble polyphenol polymers were found to have beneficial biological activity, increasing insulin-dependent glucose metabolism by roughly 20-fold in vitro (Anderson 2004). The nutrients displayed significant antioxidant activity as well, as did other phytochemicals found in cinnamon, such as epicatechin, phenol, and tannin. Moreover, scientists determined that these polyphenol polymers are able to upregulate the expression of genes involved in activating the cell membrane’s insulin receptors, thus increasing glucose uptake and lowering blood glucose levels (Imparl-Radosevich 1998).
The problem with long-term cinnamon use is the presence of highly reactive aldehyde compounds. These toxic fat-soluble compounds accumulate in the body over time. An aqueous extract of cinnamon has been identified and through a patented process, delivers cinnamon’s beneficial water-soluble nutrients while removing deleterious fat-soluble toxins.
In a recent double-blind, placebo-controlled trial (Stoecker 2010), a group of individuals (average age 61) with high blood sugar taking 500 mg daily of this form of cinnamon extract experienced an average decline of 12 mg/dL in fasting blood glucose after just two months. It also produced a significant decrease in postprandial glucose spikes (by an average of 32 mg/dL) after ingestion of 75 grams of carbohydrates. These findings support previous clinical data on similar aqueous cinnamon extracts, in which diabetic patients saw their fasting glucose drop an average of 10.3% after four months (Mang 2006).
Brown seaweed and bladderwrack. Another approach in managing glucose levels is to blunt the conversion of starches into their component sugars in the gastrointestinal tract. This can be accomplished safely and effectively by introducing natural enzyme inhibitors that halt carbohydrate metabolism in the gut. The most attractive targets are the sugar-producing alpha-amylase and alpha-glucosidase enzymes.
Extracts from a variety of seaweeds have inhibitory effects on these enzymes (Kim 2010; Apostolidis 2010; Kim 2008; Zhang 2007). Animal studies have revealed that inhibiting these enzymes lowers blood sugar levels (Heo 2009; Lamela 1989). In a recent double-blind, placebo-controlled clinical trial, a single dose of 500 mg daily of bladderwrack and seaweed significantly increased insulin sensitivity while inducing a 48.3% decline in postprandial glucose levels in healthy individuals (Lamarche 2010).
Irvingia gabonensis. Published studies show that extract of the African mango Irvingia gabonensis inhibits alpha-amylase-mediated conversion of carbohydrates into sugar (Oben 2008).
In 2006, researchers studied the effect of Irvingia in rats who were artificially induced to develop diabetes. A single oral dose of Irvingia lowered plasma glucose two hours after treatment (Ngondi 2006).
In 1990, researchers studied the effects of Irvingia on eleven human type 2 diabetics. Compared to baseline, there were significant reductions in blood triglyceride levels (16%), total cholesterol (30%), LDL (39 %), and glucose (38%), while HDL-cholesterol levels were increased by 29% after four-weeks of supplementation. These desirable biochemical effects were accompanied by improved clinical states (Adamson 1990).
Adiponectin is a hormone that plays a critical role in metabolic abnormalities associated with type 2 diabetes, obesity, and atherosclerosis (Berger 2002; Fasshauer 2004; Shand 2003; Yamauchi 2001; Kadowaki 2005; Kershaw 2004; Hotta 2001; Arita 1999; Ryo 2004; Yatagai 2003; Yamamoto 2004). Higher levels of adiponectin enhance insulin sensitivity; enhancing insulin sensitivity as we age is important to long-term metabolic health. Adipogenic transcriptional factors involved with adiponectin are also involved in the formation of new adipocytes, fat burning and endothelial function (Rosen 2000; Gustafson 2003; Oben 2008). Irvingia increases beneficial adiponectin levels and inhibits adipocyte differentiation mediated through the suppression of adipogenic transcription factors (Oben 2008).
White kidney bean. Extracts from the common white kidney bean, Phaseolus vulgaris, are powerful blockers of the enzyme alpha-amylase (Mosca 2008; Obiro 2008). White bean extract shows enormous potential for preventing the blood sugar and insulin spikes associated with many chronic health disorders (Preuss 2007).
Amylase inhibition with white bean extract has proven particularly effective in reducing glycemia (sugar load in the blood) in studies on diabetic animals. Supplementation in diabetic rats not only substantially lowered mean blood sugar levels, but it also reduced the animals’ total food and water intake (water intake is increased in untreated diabetes because of the amount lost in sugar-laden urine) (Tormo 2006).
White bean extract has yielded equally compelling results in human studies. It has been shown to diminish the effects of high-glycemic index foods (like white bread) that are notorious for producing sharp, potentially dangerous postprandial blood sugar spikes, helping to alleviate metabolic burden throughout the body (Udani 2009).
In one notable study, postprandial blood sugar levels were measured in a group of healthy subjects after consuming 50 grams of carbohydrate in the form of wheat, rice, and other high-carbohydrate plant foods (Dilawari 1981). Phaseolus vulgaris inhibited the average post-ingestion spike in blood sugar by 67%.
Green coffee extract. Coffee contains some well-studied phytochemicals such as chlorogenic acid, caffeic acid, ferulic acid, and quinic acid (Charles-Bernard 2005). Some of coffee’s most impressive effects can be seen in blood glucose management. Chlorogenic acid and caffeic acid are the two primary nutrients in coffee that benefit individuals with high blood sugar. Glucose-6-phosphatase is an enzyme crucial to the regulation of blood sugar. Since glucose generation from glycogen stored in the liver is often overactive in people with high blood sugar (Basu 2005), reducing the activity of the glucose-6-phosphatase enzyme leads to reduced blood sugar levels, with consequent clinical improvements.
Chlorogenic acid has been shown to inhibit the glucose-6-phosphatase enzyme in a dose-dependent manner, resulting in reduced glucose production (Hemmerle 1997). In a trial at the Moscow Modern Medical Center, 75 healthy volunteers were given either 90 mg chlorogenic acid daily or a placebo. Blood glucose levels of the chlorogenic acid group were 15 to 20 percent lower than those of the placebo group (Abidoff 1999). Chlorogenic acid also has an antagonistic effect on glucose transport, decreasing the intestinal absorption rate of glucose (Johnston 2003), which may help reduce blood insulin levels and minimize fat storage.
In another trial, researchers gave different dosages of green coffee bean extract, standardized for chlorogenic acid, to 56 people. Thirty-five minutes later, they gave the participants 100 grams of glucose in an oral glucose challenge test. Blood sugar levels dropped by an increasingly greater amount as the test dosage of green coffee bean extract was raised (from 200 mg to 400 mg). At the 400 mg dose, there was a full 24% decrease in blood sugar—just 30 minutes after glucose ingestion (Nagendran 2011).
Green coffee bean extract found in unroasted coffee beans, once purified and standardized, produces high levels of chlorogenic acid and other beneficial polyphenols that can suppress excess blood glucose levels. Roasting destroys much of the coffee bean’s beneficial content.
Garlic. Allium is the active component in garlic and onions. Allium compounds are sulfur-donating compounds that help reconstitute glutathione, a major internal antioxidant. This mechanism is probably responsible for allium’s positive effects. Allium has a number of positive effects that may help reduce the risk of diabetic complications, including the following:
- Reducing the risk of cardiovascular disease, including atherosclerosis (Breithaupt-Grogler 1997; Efendy 1997; Koscielny 1999; Turner 2004)
- Decreasing oxidative stress (Dhawan 2004)
- Promoting weight loss and insulin sensitivity in animal models of diabetes (Elkayam 2003)
- Lowering blood pressure (Auer 1990; Sharifi 2003; Silagy 1994; Wilburn 2004)
- Improving cholesterol profile (Durak 2004; Gardner 2001; Holzgartner 1992; Isaacsohn 1998; Kannar 2001; Kris-Etherton 2002; Mader 1990; Neil 1996; Silagy 1994; Steiner 1996; Superko 2000; Warshafsky 1993)
Green tea. The compounds in these plants, including epicatechin, catechin, gallocatechin, and epigallocatechin, are powerful antioxidants, particularly against pancreas and liver toxins (Okuda 1983). Animal studies have shown that epigallocatechins, in particular, may have a role in preventing diabetes (Crespy 2004). In studies with rats, epigallocatechins prevented cytokine-induced β-cell destruction by downregulating inducible nitric oxide synthase, which is a pro-oxidant (Kim 2004; Song 2003). This process could help slow the progression of type 1 diabetes. In vitro studies have also shown that green tea suppresses diet-induced obesity (Murase 2002), a key risk factor in developing diabetes and metabolic syndrome (Hung 2005).
Vitamin D. Vitamin D has far-reaching implications that extend beyond promoting bone health. Over the past 40 years, research has shed light on the intersecting pathways of vitamin D and many other aspects of health.
Evidence from animal experiments and human observational studies suggests that vitamin D may help prevent type I diabetes, perhaps by acting as an immune system modulator (Zittermann 2007). Researchers demonstrated that the pancreatic β-cells of mice contain receptors for 1,25-dihydroxyvitamin D. When they administered this active form of vitamin D to mice early in life, the animals demonstrated a reduced incidence of type I diabetes. However, diabetes incidence was not affected when 1,25-dihydroxyvitamin D was administered to mice later in life. Vitamin D appears to limit the expression of certain cytokines, which may prevent the autoimmune attack on pancreatic cells that can lead to diabetes (Targher 2006).
Human studies likewise suggest that vitamin D may have a protective effect against type I diabetes. In a large-scale investigation, more than 12,000 pregnant women in Finland enrolled in a trial studying the relationship between vitamin D intake and type I diabetes in infants. After one year, children who supplemented with the suggested study dose of vitamin D (2000 IU daily) had a much lower risk of type I diabetes than children who did not supplement (Levin 2005).
Vitamin D supplementation may reduce susceptibility to type II diabetes by slowing the loss of insulin sensitivity in people who show early signs of the disease. Researchers studied 314 adults without diabetes and gave them either 700 IU of vitamin D and 500 mg of calcium daily or a placebo for three years (Pittas 2007). Among subjects who had impaired (slightly elevated) fasting glucose levels at the study’s onset, those taking the active supplement had a smaller rise in glucose levels over three years than did the controls, as well as a smaller increase in insulin resistance. The researchers concluded that for older adults with impaired glucose levels, supplementing with vitamin D and calcium may help avert metabolic syndrome and type II diabetes.
Ginkgo biloba. Animal studies demonstrate that ginkgo improves glucose metabolism in muscle fibers and prevents atrophy (Punkt 1999). Animal studies also show that ginkgo biloba extracts significantly inhibit post-meal sugar levels and act as anti-hyperglycemic agents (Tanaka 2004).
Ginkgo biloba extract has been shown to prevent diabetic retinopathy in diabetic rats, suggesting a protective effect in human diabetics (Doly 1988). In a preliminary clinical trial (Huang 2004), type 2 diabetics were given ginkgo extract orally for three months, which significantly reduced free radical levels, decreased fibrinogen levels, and improved blood viscosity. Ginkgo extracts also improved retinal capillary blood flow rate in type 2 diabetic patients with retinopathy.
Ginkgo has also been observed to lower blood glucose levels. It was studied in type 2 diabetics at a dose of 120 mg for three months. Ginkgo supplementation produced an increase in liver metabolism of insulin and oral hypoglycemic medications, which corresponded to a reduction in plasma glucose levels (Kudolo 2001). Type 2 diabetics with pancreatic exhaustion received the most benefit. Ginkgo does not appear to increase beta cell production; rather it enhances liver uptake of existing insulin, thereby reducing high insulin levels.
Blueberries. Native to North America, blueberries have long been used in food preparation and for therapeutic purposes (Prett 2005). Many of the health benefits attributed to blueberries have been linked to their potent antioxidant properties. Scientists attribute these powerful antioxidant properties to polyphenols in blueberries known as anthocyanins
In published studies, blueberries block carbohydrate metabolism in the intestine by up to 90% compared with the prescription drug acarbose (Johnson 2011; Melzig 2007).
Additionally, blueberries have been shown to lower baseline blood sugar levels in those diagnosed with type 2 diabetes by 37% (Vuong 2009; Abidov 2006; Takikawa 2010).
In a double-blind, placebo-controlled study, 32 obese, insulin-resistant (pre-diabetic) adult men and women drank smoothies made with freeze-dried blueberry powder for six weeks. A placebo control group consumed smoothies without blueberry extracts (Stull 2010). Fasting blood samples were obtained with a clamp technique considered state-of-the-art for precise determination of insulin sensitivity. With no changes in body weight or composition compared to controls, the blueberry group showed a statistically significant and much greater improvement in insulin sensitivity (22.2% plus or minus 5.8%) versus the placebo arm (4.9% plus or minus 4.5%).
Vaccinium myrtillus (bilberry). Studies of diabetic rats show that bilberry decreases vascular permeability (Cohen-Boulakia 2000). Studies of diabetic mice receiving an herbal extract containing bilberry demonstrated significantly decreased blood glucose levels (Petlevski 2001; Petlevski 2003).
A double-blind, placebo-controlled trial of bilberry extract in 14 people with diabetic retinopathy or hypertensive retinopathy (damage to the retina caused by diabetes or hypertension, respectively) found significant improvements in the treated group (Bone 1997). Other open clinical trials in humans also showed benefits. A preliminary study of 31 people with retinopathy documented that bilberry reduced vascular permeability and reduced hemorrhage (Scharrer 1981).
Diabetes & Glucose Control
NOTE: Under no circumstances should people suddenly stop taking antidiabetic drugs, especially insulin. Individuals with diabetes should work closely with their healthcare provider before initiating a supplement regimen due to the potential risk of hypoglycemia.
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).
In a clinical trial in 13 subjects with type 2 diabetes, participants consumed a high-AGE meal before and after a 3-day course of benfotiamine, 1050 mg per day. The subjects’ vascular and endothelial function were assessed after both high-AGE meals. Signs of vascular dysfunction were completely prevented by benfotiamine administration, and biomarkers of endothelial dysfunction and oxidative stress were significantly reduced (Stirban 2006).
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 a climbing vine of the family Cucurbitaceae (cucumber or gourd family) that 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).
Hesperidin. Hesperidin and related flavonoids are found in a variety of plants, but especially in citrus fruits, particularly their peels (Umeno 2016; Devi 2015). Digestion of hesperidin produces a compound called hesperetin along with other metabolites. These compounds are powerful free radical scavengers and have demonstrated anti-inflammatory, insulin-sensitizing, and lipid-lowering activity (Li 2017; Roohbakhsh 2014). Findings from animal and in vitro research suggest hesperidin’s positive effects on blood glucose and lipid levels may be related in part to activation of the AMP-activated protein kinase (AMPK) pathway (Jia 2015; Rizza 2011; Zhang 2012). Accumulating evidence suggest hesperidin may help prevent and treat a number of chronic diseases associated with aging (Li 2017).
Hesperidin may protect against diabetes and its complications, partly through activation of the AMPK signaling pathway. Coincidentally, metformin, a leading diabetes medication, also activates the AMPK pathway. In a six-week randomized controlled trial on 24 diabetic participants, supplementation with 500 mg of hesperidin per day improved glycemic control, increased total antioxidant capacity, and reduced oxidative stress and DNA injury (Homayouni 2017). Using urinary hesperetin as a marker of dietary hesperidin, another group of researchers found those with the highest level of hesperidin intake had 32% lower risk of developing diabetes over 4.6 years compared to those with the lowest intake level (Sun 2015).
In a randomized controlled trial, 24 adults with metabolic syndrome were treated with 500 mg of hesperidin per day or placebo for three weeks. After a washout period, the trial was repeated with hesperidin and placebo assignments reversed. Hesperidin treatment improved endothelial function, suggesting this may be one important mechanism behind its benefit to the cardiovascular system. Hesperidin supplementation also led to a 33% reduction in median levels of the inflammatory marker high-sensitivity C-reactive protein (hs-CRP), as well as significant decreases in levels of total cholesterol, apolipoprotein B (apoB), and markers of vascular inflammation, relative to placebo (Rizza 2011). In another randomized controlled trial in overweight adults with evidence of pre-existing vascular dysfunction, 450 mg per day of a hesperidin supplement for six weeks resulted in lower blood pressure and a decrease in markers of vascular inflammation (Salden 2016). Another controlled clinical trial included 75 heart attack patients who were randomly assigned to receive 600 mg hesperidin per day or placebo for four weeks. Those taking hesperidin had significant improvements in levels of high-density lipoprotein (HDL) cholesterol and markers of vascular inflammation and fatty acid and glucose metabolism (Haidari 2015).
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. These postprandial glucose spikes increase the risk of cardiometabolic diseases not only for diabetics and prediabetics, but also for people whose fasting glucose level is in the conventional “normal” range. 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).
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).
- Specially roasted coffee and 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). Although several studies have shown conventional coffee has meaningful health benefits, consuming a coffee high in chlorogenic acid may extend these benefits further (Johnston 2003; Hemmerle 1997). Fortunately, scientists have developed a method for roasting coffee that yields brewed coffee with higher-than-typical chlorogenic acid content (Zapp 2013). Individuals who wish to attain the most benefit from coffee polyphenols should consume coffee specially prepared to ensure that chlorogenic acid is retained during the roasting process.
- 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 vesiculosusinhibited 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).In a study in diabetic mice, polyphenolic fractions prepared from brown seaweed extract were shown to improve fasting serum glucose levels and blunt the rise in blood glucose following an oral sugar challenge. Compared with untreated mice, the mice given the polyphenol extract exhibited decreased total blood cholesterol. The seaweed-derived polyphenols also restored liver glycogen (stored carbohydrate) content (Zhang 2007).
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).
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. The oral diabetes medication canagliflozin (Invokana) is also based on this mechanism (Sarnoski-Brocavich 2013; Najafian 2012; Masumoto 2009).
- 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).
- Maqui berry extract. Maqui berries (Aristotelia chilensis) are a purple-black fruit native to Chile that have garnered attention for their strong capacity to quench free radicals. They are also the richest known source of highly active polyphenolic compounds called delphinidins. When compared with other berries such as cranberries, blueberries, raspberries, and blackberries, maqui berries were found to be at least three times higher in total polyphenols and to have approximately three times greater free radical-quenching capacity (Watson 2015).In a 2014 study to investigate its effects on blood glucose control, a single 200 mg dose of a standardized maqui berry extract 30 minutes prior to ingesting a serving of white rice was found to delay and decrease the rising levels of blood glucose and insulin better than placebo in 10 volunteers with moderate glucose intolerance (Hidalgo 2014). Similarly, single doses of 60 mg, 120 mg, and 180 mg taken one hour before oral glucose tolerance testing effectively improved fasting blood glucose levels as well as glucose and insulin responses in pre-diabetic individuals, with 180 mg having the greatest impact on blood glucose levels (Alvarado, Leschot 2016). To assess its long-term effects, a group of 31 moderately glucose-intolerant subjects were treated with 180 mg standardized maqui berry extract daily for three months. Result showed progressive decreases in HbA1c values at 30, 60, and 90 days. In addition, LDL-cholesterol levels were lower and HDL-cholesterol levels were higher at the end of the trial, indicating improved lipid metabolism (Alvarado, Schoenlau 2016).Several mechanisms may contribute to the positive effects of maqui berries on glucose regulation. Findings from preclinical research suggest maqui berry extract may decrease glucose production in the liver and increase insulin sensitivity (Rojo 2012). In an animal model of diabetes, maqui berry extract reduced intestinal absorption of glucose (Hidalgo 2014). Other research has indicated that maqui berry extract inhibits the inflammatory signaling between fat cells and immune cells that is associated with the development of insulin resistance (Reyes-Farias 2015).
- Clove bud extract. Clove (Syzygium aromaticum), a well-known spice, has shown potential to improve glucose levels and aid in overall metabolism (Tu 2014; Kuroda 2012). An ethanol extract of clove flower buds was found to decrease blood glucose levels in diabetic mice (Kuroda 2012); in diabetic and lipid-disordered mice, supplementation with an alcohol clove extract resulted in lower glucose, triglyceride, free fatty acid, HbA1C levels (Sanae 2014). Its positive effects on metabolism were further demonstrated in an animal model of obesity, in which treatment with an alcohol extract of clove reduced the negative impact of a high-fat diet on body weight as well as lipid, glucose, and insulin levels (Jung 2012).Findings from a clinical study on human subjects, which are not yet published, add more support for the potential anti-diabetic effects of clove. After 30 days of supplementation with 250 mg per day of a water extract of clove, participants had lower after-meal blood glucose levels. Furthermore, participants with higher blood glucose levels before the trial experienced greater reductions in after-meal glucose levels (AKAY 2017).In vitro research has shown that a clove extract has insulin-like effects on liver cells, inhibiting the breakdown of stored carbohydrates into glucose and preventing a subsequent rise in levels of circulating glucose (Prasad 2005; Sanae 2014). In muscle cells, clove extract stimulated the conversion of glucose into energy and enhanced mitochondrial function (Tu 2014). Some individual compounds from an ethanol extract of clove have been found to activate cellular pathways that increase glucose and lipid uptake (Kuroda 2012).
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). Studies that supplemented type 2 diabetics and healthy individuals with 1‒6 g of cinnamon reported lower levels of fasting glucose, HbA1C and after-meal glucose and insulin concentrations, as well as improvements in insulin sensitivity. These effects have been demonstrated even in those already taking glucose-lowering medication (Lu 2012; Davis 2011; Magistrelli 2012; Hoehn 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).
A randomized placebo-controlled trial tested a combination of EPA, DHA, and the plant-sourced omega-3 fatty acid alpha-linolenic acid in over 1000 diabetics with a history of heart attack. Subjects receiving the omega-3 preparation had 84% lower risk of a ventricular arrhythmic event, and 72% lower risk of a combined outcome of fatal heart attacks and ventricular arrhythmic events (Kromhout 2011).
Omega-3 fatty acids from fish oil, DHA and EPA, appear to protect against some of the changes in blood vessel function associated with post-meal blood sugar surges. A six-week trial in 34 subjects with type 2 diabetes found omega-3 fatty acid supplementation significantly protected against post-meal dysfunction in small and large blood vessels (Stirban 2010).
A review found greater consumption of omega-3 fats from fish was associated with a 15‒19% lower rate of death from cardiovascular disease, as well as lower triglycerides, decreased inflammation, lower blood pressure, and diminished platelet activation and aggregation (McEwen 2010).
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).
Magnesium plays a critical role in cardiovascular health. A study in over 13 000 US adults found women with the highest serum magnesium levels had a 56% lower risk of coronary artery disease compared with those with the lowest levels; in men, those with the highest serum magnesium had a 27% less risk compared with those whose levels were lowest. Similarly, women with the lowest dietary magnesium intake had a more than 1.3-fold greater risk of cardiovascular disease (Kolte 2014). One study found that, in diabetic patients with coronary artery or peripheral vascular disease, there was a significant correlation between low magnesium and high fasting plasma glucose and HbA1C (Agrawal 2011).
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).
The reduced form of CoQ10—ubiquinol— is absorbed more efficiently than the ubiquinone form (Langsjoen 2008; Hosoe 2007).
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, simply because the whole dose consists of the active “R” molecule. Look for the “R” label to ensure you are getting the most potent form of lipoic acid (Smith 2005; Streeper 1997).
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).
In a rodent model of diet-induced inflammation similar to that observed in diabetes, the addition of blueberry powder to the animals’ diet prevented inflammatory changes, and protected the mice from developing insulin resistance and high blood sugar (DeFuria 2009). Soybean flour enriched with a concentrate of blueberry polyphenols was shown to reduce hyperglycemia, weight gain, and serum cholesterol in mice. The blueberry-fortified flour also reduced glucose production in the liver by 24‒74% (Roopchand 2013).
In cell culture studies, an anthocyanin-rich blueberry extract exhibited insulin-sensitizing properties, conferred protection against glucose and fatty acid toxicity, and enhanced proliferation of insulin-producing pancreatic beta cells (Martineau 2006; Liu, Gao 2015).
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).
A randomized controlled trial administered 2 g of grape polyphenols per day to healthy but overweight first-degree relatives of type 2 diabetics for eight weeks. Subjects were then challenged with substantial doses of fructose, the sugar present in fruit juices and many sweetened beverages. In the placebo group, the fructose challenge resulted in increased oxidative stress and decreased insulin sensitivity and mitochondrial activity. All of these negative effects were prevented in the polyphenol group (Hokayem 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).
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).
Disclaimer and Safety Information
This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the treatments discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.
The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. The publisher has not performed independent verification of the data contained herein, and expressly disclaim responsibility for any error in literature.
Diabetes & Glucose Control
Life Extension Suggestions
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:
- R-lipoic acid: 240 – 480 mg daily
- L-carnitine: 500 – 1000 mg twice daily
- Carnosine: 500 mg twice daily
- Chromium: 500 – 1000 mcg daily
- CoQ10(in the form of ubiquinol): 100 to 300 mg daily
- DHEA: 15 – 75 mg early in the day, followed by blood testing after three to six weeks to ensure optimal levels
- EPA/DHA: 1400 mg EPA and 1000 mg DHA daily
- Fiber(guar, pectin, propolmannan, or oat bran): 20 to 30 g daily at least, up to 50 g daily.
- Propolmannan: 2 grams twice daily
- GLA: 900 – 1800 mg daily
- Quercetin: 500 mg daily
- Magnesium: 140 mg daily as magnesium L-threonate; 320 mg daily as magnesium citrate
- NAC: 500 – 1000 mg daily
- Silymarin: containing 750 mg Silybum marianum standardized to 80 percent Silymarin, 30 percent Silibinin, and 8% Isosilybin A and Isosilybin B
- Vitamin C: at least 2000 mg daily
- Vitamin E: 400 IU daily (with 200 mg gamma tocopherol)
- Garlic: 1200 mg daily
- Green tea extract: 725 mg green tea extract (minimum 93 percent polyphenols)
- Ginkgo biloba: 120 mg daily
- Bilberry extract: 100 mg daily
- B complex: Containing the entire B family, including biotin and niacin
- Cinnamon extract: 175 mg (Cinnamomum cassia) standardized to 2.5% (4.375 mg) A-type polymers three times daily
- Green coffee bean extract: 200 – 400 mg (standardized to contain chlorogenic acid) three times a day
- Vitamin D: 5000 – 10 000 IU daily
- Brown seaweed and bladderwrack: 100 mg three times a day
- Irvingia gabonensis: 150 mg twice a day
- White kidney bean: 445 mg twice a day
- Blueberry:standardized to contain 50 mg 3,4 – caffeoylquinic (chlorogenic) acid, and 50 mg myricetin) or 22.5 g blueberry bioactive freeze dried powder
In addition, the following blood testing resources may be helpful:
- Fasting glucose
- Postprandial glucose test
- Fasting insulin
- Vitamin D
- Omega Score®