Dietary Supplements and Diabetes: Postprandial Approaches

Of the various approaches to dealing with blood glucose levels, postprandial (after eating) management techniques are among the more interesting.

This does not deny the value of such alternatives as diet and exercise; stimulation of insulin production; improvement of insulin sensitivity; and increasing levels of adiponectin, a protein produced by fat cells that may play an important role in the development of obesity and insulin-resistant diabetes. This article, however, will focus on postprandial options.

“Postprandial glucose management is the key to controlling risks due to diabetes,” states R.V. Venkatesh, managing director of the Gencor Pacific Group (Anaheim, CA).

He cites studies showing that postprandial hyperglycemia is closely correlated to elevated glycosylated hemoglobin (HbA1C) levels. HbA1C provides a measure of the degree by which hemoglobin is glycosylated. Glycosylation is the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules in red blood cells. This glycosylation, linked to postprandial hyperglycemia, “is irreversible, and it leads to vascular problems, increasing risks of cardiovascular disease,” says Venkatesh.

 

Postprandial Glucose Control

According to Venkatesh, Gencor Pacific has two products targeted at postprandial glucose control. The first is the herbal extract Coccinia cordifolia (synonym Coccinia indica), sold under the brand name Gencinia.

Venkatesh reports that Gencinia has shown “excellent control of fasting and postprandial blood-glucose reduction” in a double-blind, randomized, placebo-controlled clinical study, peer-reviewed and published in the journal Diabetes Care. It has been postulated, the executive suggests, that the ingredients present in Coccinia cordifolia “[act] like insulin, correcting the elevated enzymes glucose-6-phospatase and lactose dehydrogenase in the glycolic pathway and [restoring] the lipoprotein lipase activity in the lypolitic pathway with the control of hyperglycemia in diabetes.”

Gencor Pacific’s second product in this area is an extract from the seeds of fenugreek (Trigonella foenum graecum), which is sold under the brand name Trigogen. Venkatesh says that an unpublished multicenter clinical study done on 120 patients showed statistically significant reduction in fasting and postprandial glucose levels and glycosylated hemoglobin levels. According to the Gencor Pacific spokesperson, fenugreek is a well-researched herb for blood sugar control, with numerous published studies, as well as the unpublished one cited above.

“The period right after eating is prone to glucose spikes, particularly from consumption of highly refined carbohydrates and sugars,” explains Mitch Skop, senior director of new product development for Kearny, NJ-based Pharmachem Laboratories. “Overall, consumers of all ages are more on the go than ever and do not take the time to prepare and eat nutritious meals. This aspect of lifestyle is not likely to change, so it opens the doors for manufacturers to provide convenient, supplemental dietary tools that can be quickly taken with water before meals or combined with food to aid in glucose management.”

According to Skop, Pharmachem’s Phase 2 Carb Controller is a white bean extract clinically shown to reduce the digestion of starch in carb-rich meals. It works by temporarily inhibiting alpha-amylase, the enzyme that digests starch-so that less starch is digested and converted to sugar. Skop cites over a dozen human clinical trials showing Phase 2 to be safe and effective. He adds, “It is the only dietary ingredient with two separate structure-function claims: ‘May reduce the enzymatic digestion of dietary starches,’ and ‘May aid in weight control when used in conjunction with a sensible diet and exercise.’”

In addition, says Skop, Pharmachem offers Phase 3 Sugar Controller, a combination formula of L-arabinose (which inhibits the enzyme sucrase, delaying the digestion and absorption of sucrose and its transformation into fat) and the company’s own, patented Food-Bound Chromium (which uses a pre-chelation technology to make chromium more digestible). Phase 3 is intended to combine both the glucose absorption benefits of L-arabinose and the insulin-control capability of chromium.

Noting that postprandial glucose management is “very crucial in diabetes,” David Romeo, managing director of Nutraceuticals International (Elmwood Park, NJ), says his company has a wide range of ingredients that can help control postprandial glucose.

Herbal extracts include Gymnema sylvestre, bitter melon (Momordica charantia), jamun (Syzgium cumini), cinnamon bark, Salacia oblonga, and banaba or crepe myrtle (Musa paradisiaca) that, in Romeo’s words, “work to stimulate insulin mechanisms to help manage blood glucose level.”

In addition, says Romeo, “We offer white kidney bean extract, which has been said to have alpha-amylase–blocking properties and will not convert starch to glucose, as well as fenugreek fiber and chicory fiber (Cichorium intybus), which is believed to help reduce intestinal absorption of glucose.”

At Shoreview, MN–based Nutra Bridge, president Scott Steil says the leading blood glucose control product is InSea2, exclusively marketed by Nutra Bridge in North America and developed by InnoVactiv (Rimouski, QC, Canada). Steil says that the newly launched ingredient, which is made from two wild brown seaweeds harvested from a UNESCO (United Nations Educational, Scientific, and Cultural Organization) private reserve, “significantly blocks both alpha-amylase and alpha-glucosidase enzymes. In other words, it blocks the breakdown of both starch and table sugar. Given that it is almost impossible to avoid the consumption of starch and complex carbs in today’s diet, supplementing with InSea2 can reduce the quick spike in blood glucose and insulin associated with these compounds.”

He adds that specific benefits associated with InSea2 usage include the following: reduction of glucose levels by 48%, peak insulin levels by 22%, and total insulin levels by 12%; increases of insulin sensitivity by 8% versus placebo; elimination of the period of hypoglycemia that is common after a high-glycemic-index meal; and ease of use (just take 250 to 500 mg prior to eating).

Banaba Leaf Extract

Steve Holtby, president and CEO of Los Angeles, CA–based Soft Gel Technologies Inc., says, “In type 2 diabetes, peak blood glucose levels typically occur one to two hours after a meal, are much higher than normal, and are slow to return to baseline values. This results in sustained hyperglycemia, which is associated with increased oxidative stress, impaired endothelial function, and other deleterious effects on the vascular system. Effective treatment for postprandial hyperglycemia is therefore a major target for treatment to reduce long-term risks and complications of hyperglycemia.”

As Holtby explains, the goals are to avoid “microvascular and macrovascular complications, lower insulin resistance, restore normal insulin secretion, and avoid complications in the offspring of women with diabetes. The effects of postprandial hyperglycemia on the development of microvascular complications of diabetes-retinopathy, nephropathy, and neuropathy-have been well documented.”

Soft Gel Technologies’ lead product in this category is GlucoHelp banaba leaf extract, a proprietary extract that is manufactured in Japan and standardized to 18% corosolic acid-a key bioactive constituent.

According to Holtby, two human clinical studies have shown that GlucoHelp significantly lowers fasting blood glucose levels, significantly lowers blood glucose levels following a starchy meal, and improves clinical symptoms of diabetes.

The Soft Gel Technologies executive offers the following insight on how banaba leaf extract works: Stored within the cells of the body are specialized carrier proteins known as glucose transporter proteins, or GLUT, which transport glucose from the blood into the cells. One type of GLUT transporter, known as GLUT4, is present in fat cells, skeletal muscle cells, and cardio-muscle cells. If a lot of GLUT4 transporters are waiting at the cell membrane “doors,” they can let glucose in. But if most of them are sequestered away in the inner part of the cell, glucose gets locked out. In a healthy body, insulin is the “key” that unlocks the cell doors, allowing glucose to enter. In cases of insulin resistance, GLUT4 transporters don’t respond properly to insulin.

What is unique about banaba leaf, says Holtby, is that two of its bioactive compounds-corosolic acid and ellagitannins-”pinch hit” for insulin. Both constituents direct GLUT4 to move to the cell membrane and activate it to incorporate glucose into the cell. Specifically, corosolic acid has been shown to activate GLUT4 in skeletal muscle cells, while ellagitannins have been shown to activate GLUT4 in fat cells. The net effect is that more glucose enters the cells, reducing the level of sugar in the blood.
 

Ayurvedic Approaches

Although it may sometimes seem that Western culture “invented” diabetes, that simply isn’t so. Ayurvedic practitioners have been battling this deadly illness for many centuries. Sabinsa Corp., an East Windsor, NJ, ingredient supplier, has deep roots in Indian medicine. It, too, has addressed the issues of blood glucose control.

N. Kalyanam, PhD, president of the company’s New Jersey research and development effort, says, “Postprandial hyperglycemia is one of the earliest abnormalities of glucose homeostasis associated with type 2 diabetes and is markedly exaggerated in diabetic patients with fasting hyperglycemia.”

Among the products his company offers are alpha-lipoic acid, Bis glycinato oxovanadium, FenuFibers, GS4 PLUS, Momordicin, Silbinol, Tulsi extract, Tinofolin, Salaretin, and Saberry. According to Kalyanam, each of these proprietary, branded ingredients is supported by “substantiated structural and functional claims.”

According to Kalyanam, alpha-lipoic acid helps break down sugars so that energy can be produced from them through cellular respiration.

Bis glycinato oxovanadium is a dark gray to grayish-black granular powder with the vanadium content not less than 20% on anhydrous basis. Kalyanam cites research done over the past century, which validated that vanadium may activate insulin receptors, and through this effect exert insulin-like action. He says, “Both preclinical and clinical studies have demonstrated that vanadium has a potential role in the management of both type 1 and type 2 diabetes.”

The Sabinsa executive says, “Fenugreek has been found to lower serum glucose levels both acutely and chronically. Studies have shown that this herb improves both glycemic control and insulin resistance.” He describes FenuFibers as the “fiber-rich fraction obtained from fenugreek seeds.”

Obtained from the plant Gymnema sylvestre, Sabinsa’s GS4 PLUS is standardized to contain 25% and 75% gymnemic acids. Kalyanam says, “Extracts of G. sylvestre have been used for the treatment of type 2 diabetes in India for centuries. The effects of Gymnema extract on plasma insulin, C-peptide, and glucose in a small cohort of patients with type 2 diabetes have been reported. Oral administration induced significant increases in circulating insulin and C-peptide, which were associated with significant reductions in fasting and postprandial blood glucose.”

Sabinsa’s Momordicin is sourced from Momordica charantia, whose fruit juice has been shown to reduce blood glucose levels, improve body weight, and increase glucose tolerance.

Kalyanam describes Silbinol as a proprietary natural pterostilbene taken from the bark and the heartwood of the Indian Kino tree (Pterocarpus marsupium). When tested under uncontrolled conditions in subjects with type 2 diabetes, he adds, concentrated extracts have decreased fasting blood glucose levels (~30 mg/dl), postprandial blood glucose (~45 mg/dl), and hemoglobin A1c (0.4%).

Tulsi extract offered by Sabinsa contains essential oils and produces caryophyllene, eugenol, and methyl eugenol. Kalyanam says, “These oils are thought to improve pancreatic function by stimulating insulin production.” In rats with alloxan-induced diabetes, extracts of Tinospora cordifolia have been shown to reduce blood glucose levels. Kalyaman identifies Sabinsa’s Tinofolin as a standardized extract of T. cordifolia.

The Sabinsa spokesperson says the company’s Salaretin is “an alpha-glucosidase and aldose reductase inhibitor known to control blood glucose levels, obtained from Salacia reticulata.” It is standardized to contain at least 1% mangiferin and 20% tripterpenoid saponins. In ayurvedic practice, he adds, S. reticulata has been used as an oral anti-diabetic agent.

An extract of fruits of Emblica officinalis (synonymous with Phyllanthus emblica and more commonly known as amla), Sabinsa’s Saberry has been researched in in-house studies in which it relieved oxidative stress and improved glucose metabolism, says Kalyanam.

Looking ahead, Kalyanam concludes, “The future of dietary supplements in the management of postprandial blood glucose control in the coming years may well be immense in scope and potential by tapping the supplement armamentarium and natural resources for leads in blood sugar support.”

Sidebar 1: Diabetes Statistics

Sometimes it seems there are only two types of people in the United States-those who already have diabetes and those on their way to getting it. The statistics are appalling.

• Nearly 26 million Americans of all ages are diabetic, and 79 million people have what doctors call “pre-diabetes,” according to 2011 estimates released by the U.S. Centers for Disease Control and Prevention (CDC) on January 26.

• The National Diabetes Education Program (NDEP)-a partnership of the National Institutes of Health (NIH), the CDC, and more than 200 public and private organizations-reports that diabetes is the nation’s seventh leading cause of death.

• More than 70 million Americans are insulin-resistant, and 54 million are pre-diabetic, according to the American Diabetes Association (ADA). Sadly, the vast majority of them don’t even know it.

• A 2003 prediction by the ADA indicates that one in three children born in 2000 will develop diabetes in his or her lifetime.

• The CDC predicts that diabetes cases will double, or even triple, by 2050. By the same year, it is possible that as much as half the U.S. population will have the disease.

• CDC data also notes that diabetes is the number one reason for adult blindness, kidney failure, and limb amputation, and is a large contributor to heart attacks and strokes. It is also now linked to a form of dementia, some forms of cancer, and some forms of lung disease.

• The total estimated cost of dealing with diabetes stood at $174 billion in 2007. Some have even called diabetes the disease that will break the U.S. healthcare bank.

• People with diagnosed diabetes, on average, have medical expenditures that are 2.3 times higher than expenditures would be in the absence of diabetes. Already, one in 10 healthcare dollars spent in the United States is attributed to diabetes, and this doubles to $1 in every $5 for someone with diagnosed diabetes.

• Ironically, this horror story for patients, their families, and the nation may hold good news for those in the business of fighting diabetes. In October 2010, Kalorama Information, a research organization with offices in Rockville, MD, and New York, NY, called diabetes “a ‘safe bet’ development area” and “one of the fastest-growing markets within the pharmaceutical sector.”

• The dietary supplement industry also has benefited from the diabetes epidemic. In 2009, the last full year for which statistics are available, Nutrition Business Journal said that sales of supplements for diabetes condition-specific use reached an estimated $970 million. This was an increase of 3% over 2008. 

Sidebar 2: Hi-Maize Resistant Starch for Diabetes

In the struggle against diabetes, numerous natural approaches have been tried. Diet and exercise is always a starting point, and healthy eating must be adhered to regardless of what other therapies are being used. Many also promote a regimen of products that have a low glycemic index-while others contend that what really matters is glycemic load or glycemic response.

National Starch, for example, offers Hi-maize resistant starch, a natural type of insoluble dietary fiber, for glycemic management. According to Rhonda Witwer, senior business development manager for the Bridgewater, NJ, company, “Hi-maize is approximately 40% slowly digested carbohydrates (digested lower within the small intestine versus high-glycemic carbohydrates) and 60% insoluble dietary fiber (fermented throughout the entire large intestine).”

Witwer says published clinical trials show that although Hi-maize does not consistently lower the glycemic index of foods, it does result in a reduced glycemic response and increased insulin sensitivity, which, she notes, not only leads to maintenance of healthy blood sugar levels, but also is related to inflammation, cancer, and other metabolic benefits.

According to Witwer, Hi-maize resistant starch easily replaces part of the flour in everyday foods without changing their taste, texture, or appearance. It can also be mixed into smoothies or mixed into oatmeal for an easy nutritional boost.

Sidebar 3: High-Glycemic Vegetables

By Isaac Eliaz, MD

Prediabetes or metabolic syndrome is characterized by uncontrollable blood glucose, stubborn weight gain, elevated blood pressure and cholesterol, and a host of other serious health risks. If left untreated, the end result can be full-blown diabetes and all of the life-threatening conditions that are associated with this rising epidemic. Recognizing the early signs and taking the right steps to strengthen your systems where they need it most can help you take back your metabolic health and beat the disease before it begins.

A healthy diet is the number one tool in the prevention and management of “pre-diabetes”/metabolic syndrome and type 2 diabetes. One of the most important things to consider when evaluating your diet is the glycemic index score of each food, which compares how quickly individual foods turn into sugar in the bloodstream. In addition to white breads, refined carbohydrates, and sweets, other types of foods are unexpectedly also high on the glycemic index scale-even certain types of vegetables.

Eating vegetables regularly can provide numerous health benefits due to their content of vitamins, minerals, and countless other phytonutrients. However, some vegetables are higher on the gylcemic index scale than others. For the most part, high-glycemic vegetables include those that are loaded in starch and sugars, such as potatoes, corn, beets, carrots, parsnips, turnips, and squash. These vegetables have an important nutritional and health value and can be taken with proteins or other vegetables that can slow down the rate of glucose absorption.

Eating too many high-glycemic foods over time can disrupt the delicate balance of insulin and glucose within the body. Glucose that is not immediately used is stored and can contribute to weight gain, or worse, circulate freely in the bloodstream and lead to insulin resistance, a symptom of metabolic syndrome and a precursor to diabetes. Protect your metabolic health by keeping insulin and blood glucose levels balanced with a low-glycemic diet, regular exercise, and a healthy lifestyle, including proper stress management.

Isaac Eliaz, MD, is an author, lecturer, researcher, product formulator, and clinical practitioner. He has been a pioneer in the field of integrative medicine since the early 1980s. For more health and wellness information, visit www.dreliaz.org.

Sidebar 4: New Glucose-Control Studies

Even as this is being written, not just one someone, but many someones, are working diligently to discover any possible nuance in how to tame America’s runaway diabetes phenomenon. A major breakthrough is hard to come by, but every incremental advance is worthwhile. Here are two items that made news last year.

Seaweed: A study published in Food Chemistry suggested that phenolic-rich extracts found in four species of edible seaweed are worth some time and attention. The research team, led by Felix Nwosu, reported, “This paper outlines potential biological activities of polyphenols from edible seaweeds and, in particular, suggests that phlorotannin components of Ascophyllum nodosum have potential anti-diabetic effects through the inhibition of both alpha-amylase and alpha-glucosidase.”

It is well known that seaweed and other microalgae figure importantly in diets consumed throughout the Far East and that diabetes is less prevalent in that part of the world.

Nwosu and his colleagues identified extracts from Palmaria palmata, Ascophyllum nodosum, and Alaria esculenta as helping to inhibit alpha-amylase. Only Ascophyllum extracts appeared to affect alpha-glucosidase, the other key enzyme involved in starch digestion and regulation of blood glucose.

Adiponectin: Elizabeth Fragopoulou and colleagues, writing in the April 2010 issue of the Journal of Nutritional Biochemistry, associated consumption of a Mediterranean diet with increased levels of adiponectin, a protein produced in large quantities by fat cells called adipocytes.

It is well-known to the point of becoming a cliché that the Mediterranean diet-rich in fruits, vegetables, nuts, grains, and seafood-is exalted for health benefits connected to a long list of diseases.