By Sean Moloughney, Editor10.02.17
One of the most significant global health epidemics of the 21st century, about 415 million adults have diabetes, and this number could rise to 642 million by 2040, according to the International Diabetes Federation. Diabetic patients are at higher risk for a range of health complications, including cardiovascular disease, kidney failure, blindness, and peripheral neuropathy.
Additionally, many consumers have prediabetes, a condition where blood sugar levels are higher than normal but not yet high enough to be type 2 diabetes. Without lifestyle changes through, people with prediabetes are likely to progress to type 2 diabetes.
Consumers face many challenges when it comes to managing these health conditions, as they require life-long commitments that often lead to physical and mental struggles, said Shaheen Majeed, worldwide president, Sabinsa, East Windsor, NJ. “The most common challenges faced by such patients include difficulty in maintaining healthy blood sugar levels given that they can fluctuate unexpectedly at times, failing to identify foods with high levels of sugar and carbohydrates, lack of physical exercise, etc.”
Blood sugar management is not easy for many consumers to understand, said Rhonda Witwer, vice president of marketing for start-up ingredient technology company International Agriculture Group (IAG). “It is not just about sugar or glucose in the blood (which doctors talk about and measure); it is really about how insulin controls blood sugar levels. This makes it more complicated for consumers. People do not generally talk about insulin. Doctors do not directly measure it and it has remained an invisible but critical part of our metabolism.”
Insulin sensitivity may degrade for 10-15 years before someone is diagnosed with type 2 diabetes, she continued. “Blood sugar is the last biomarker affected by the loss of blood sugar control. Insulin sensitivity is the first biomarker affected. We do not measure insulin sensitivity, however, so it remains invisible.”
Insulin resistance means that someone has higher than normal levels of insulin, especially after eating carbohydrate-rich foods. High levels of insulin trigger the body to store fat and prevent fat from being utilized as energy by the body, Ms. Witwer explained. “Thus, weight gain and/or an inability to lose weight may be an indication that someone is insulin resistant. For instance, some people are sensitive to carbohydrates and will easily gain weight after eating refined carbohydrate rich foods. This is likely due to the high insulin spike that occurs after the consumption of refined carbohydrates, which promotes fat storage. While the weight gain is commonly attributed to aging or getting older, it is more likely due to insulin resistance, a condition that can be changed.”
The Sins of Sugar
Sugar has become public enemy number one in terms of public health evaluation. Whereas fats were once vilified, leading to many low-fat formulations with higher sugar contents, research and public understanding has shifted.
The Lancet recently published results from the Prospective Urban Rural Epidemiology (PURE) study, in which researchers assessed dietary intake of 135,335 individuals aged 35–70 years (enrolled between Jan 1, 2003 and March 31, 2013) in 18 countries using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorized into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. Researchers assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality.
Results indicated that high carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. “Global dietary guidelines should be reconsidered in light of these findings,” researchers concluded.
“The PURE study results show that subjects eating high amounts of carbohydrates were 28% more at risk of total mortality than subjects in the lowest carb intake quintile,” noted Jocelyn Bérubé, executive & scientific director, Health & Nutrition, InnoVactiv Inc., Rimouski, Quebec, Canada. “Risks of major cardiovascular diseases increased sharply in subjects consuming more than 70% of their calories as carbohydrates (about one quarter of subjects were in that 70%-and-up range). Paradoxically, subjects eating the highest amounts of dietary fats (and of each type of fat) had lower odds of total mortality and non-cardiovascular mortality compared to subjects eating the lowest amount.”
For nearly half a century, the spotlight has been on fats when it comes to optimizing diet, he added. “As a result, an ever-increasing range of low-fat foods allowed people to indulge while giving them a clear conscience about their health. We now know that these low-fat foods were created by substituting fats with sugar and other types of carbohydrates, such as starch and dextrins. These sugars brought desirable attributes to foods that were lost when removing fats: taste and texture. As we cut the fat out of our lives, we paved a golden path for an ever-increasing intake of sugar. This study indicates that high dietary carbohydrate intake needs to be addressed to maintain health. The golden years of the low-fat trends should be a thing of the past.”
Poor glucose control and insulin resistance are two of the most pervasive biomarkers associated with chronic diseases affecting over 80% of Americans, according to Mitch Skop, senior director of new product development, Pharmachem Laboratories Inc., Kearny, NJ. “Insulin resistance occurs for a variety of reasons, but primarily it’s due to diets that tend to be abundant in starchy foods with high sugar content. Researchers have suggested that an important factor of this epidemic is the increased intake of simple carbohydrates that are rapidly absorbed (particularly sugars).”
Simple carbohydrates like sugar are quickly converted into glucose, he continued. “After eating, the pancreas detects this sudden rise in glucose and tries to regulate it by excreting insulin into the bloodstream. A rise in insulin signals the body to stop burning stored fat and begin to burn circulating glucose. Until glucose levels return to normal, the body is more efficient at storing fat than burning it.”
A sensible diet and exercise plan is the cornerstone of metabolic management, he said. “But if we can begin to safely impact the absorption of glucose, help insulin receptors work more efficiently, and at the same time increase the amount of resistant starch that gets delivered to the large intestine (to feed the microbiota and modulate the gut hormones responsible for appetite)—there is a better chance of staving off high blood sugar and the negative impacts it brings.”
Once high blood sugar sets in, the pancreas is stressed to produce and release exorbitant amounts of insulin to keep up, to shuttle the glucose to where it belongs, said Annie Eng, CEO, HP Ingredients, Bradenton, FL. “The challenges arise in the symptoms that dramatically impact quality of life: excessive thirst, excessive need to urinate, headaches and blurred vision, fatigue and trouble concentrating, and believe it or not, loss of weight. Once a diagnosis of superlatively high fasting blood glucose is given, the individual then must make significant lifestyle changes, giving rise to other mild to moderate challenges including higher stress and low mood.”
Lynda Doyle, senior vice president of global marketing, OmniActive Health Technologies, Morristown, NJ, said a lack of symptoms associated with high blood sugar presents a challenge to consumers. “Most people may be unaware that they have high blood sugar until their doctor tells them or after symptoms develop. Another big challenge is the increasing prevalence of overweight/obese individuals, which impacts blood sugar management. It’s estimated that almost half of the global population may be obese or overweight by 2030 (according to the Global Panel on Agriculture and Food Systems for Nutrition).”
Dietary intervention can also make management difficult since sugar is such a pervasive ingredient and not always readily apparent in foods, she added. “Consumers may find that avoiding sugar is too onerous and eventually give up. Finally, lack of exercise can impact blood sugar too—whether through its effect on weight gain or other mechanisms. Most likely, it is a combination of some or all of these factors that presents a challenge to consumers trying to manage their blood sugar that in many cases leads to non-compliance.”
Diet and lifestyle changes aimed at weight loss are known to be effective, but they are difficult to sustain over the long-term due to a compensatory increase in appetite and food intake, said Jon Peters, president, BENEO Inc., Parsippany, NJ. “As consumers become more sophisticated on how they approach their diets and nutritional choices, they expect food to contribute to their overall fitness. They will become increasingly interested in the role carbohydrates can play in terms of digestibility, caloric value, glycemic response, or the ability to influence the use of fat or glycogen storages.”
Opportunities & Challenges for Nutraceuticals
To be clear, diabetes is a life-threatening disease and by law, under the Dietary Supplement Health and Education Act (DSHEA), dietary supplements cannot make claims to mitigate, treat, cure, or prevent disease.
“We can, however, help healthy people reduce their risk of getting into trouble with their serum glucose with natural ingredients,” said Mr. Skop. “There are many hidden sugars in the foods we eat. Cooking from scratch—using whole, raw foods enhanced with natural culinary spices—is practiced by very few Americans.”
Many products claim to help manage healthy blood sugar levels. However, product developers face several challenges, according to Sabinsa’s Mr. Majeed, including selecting proper ingredients that are safe and backed by science-based claims, finalizing optimally effective dosages as well as end-product format (e.g., nutrition bar, shake, capsule/tablet).
“Another major issue is to deal with adulteration, or substitution of original natural actives with spurious or look-alike substandard ingredients,” he added. “And this can be addressed by carrying out proper tests before including such ingredients into the intended formulation, and carefully sourcing only from suppliers with an established track record.”
According to Bill Levi, vice president of operations, Nutrition 21, Purchase, NY, the two largest issues that product developers are facing with respect to the blood sugar management market revolve around specific demographics of patients as well as the reluctance of the medical community to recommend natural alternatives to treatment. “Patients who have blood glucose management issues have typically led a sedentary lifestyle combined with poor dietary choices. They aren’t as educated on what natural products exist on the market to help with their condition. They rely heavily on the opinions and recommendations of their physicians, rarely venturing out on their own to find non-pharmaceutical supplemental solutions. Additionally, the medical community is hesitant to recommend natural supplements over pharmaceuticals to patients as a treatment option for the management of their condition. This leads patients to be much more hesitant when it comes to purchasing or even considering any form of natural supplement or nutraceutical.”
Historically, people looking for blood sugar supplements were encouraged to do so because of family history of diabetes, or because they were overweight and concerned about their higher risk of long-term blood glucose issues, said Mr. Bérubé. “One of the challenges we face in attracting new consumers to this market is that undesired blood glucose levels do not necessarily generate symptoms, and when they do these symptoms are being wrongly associated with other conditions.”
For example, many people may feel a drop in mental energy after large meals. “Popular belief is that after a meal, our digestive tract requires an increasing blood flow to support its digestive efforts, which in turn deprives our brain of much needed energy. This myth has been proven wrong many times, with studies showing that brain blood flow is always prioritized over other organs, even during high-intensity physical exercise. Very few people actually know that blood glucose swings are responsible for these transient ‘food comas,’ and that more control over blood glucose after meals can actually help sustain optimal cognitive function throughout the day.”
Traditionally, blood sugar management has been linked to a disease state, such as diabetes which has been a challenge for supplement manufacturers that are looking to formulate a viable product, said Ms. Doyle. “However, with the rise in popularity of no/low-carb and paleo diets, consumer interest has been piqued and awareness of the health benefits of maintaining healthy blood sugar for not only weight management but for overall health and well-being has become mainstream. This has the market poised to break into new, exciting opportunities with expanded demographics and novel deliveries. For instance, OmniLean (the company’s proprietary extract of Salacia chinensis) has tremendous promise because of its formulation flexibility which includes tablets and capsules, as well as functional foods and beverages.”
Although historically, individuals with blood glucose issues were unaware or uninformed about the benefits of adding a nutraceutical into their daily regimen, more recently, consumers have been more inclined to educate themselves on what to look for in specific nutritional supplements, she added. “Additionally, over time, there has been some turn over in the traditional medical community allowing for an upsurge of homeopathic or more naturally inclined physicians, who are open to exploring nutraceuticals as a recommended option for their patients.”
Keeping weight in check and being physically active can help prevent many cases of diabetes, however, because a balanced diet contributes to the body’s glycemic control, it can also help to prevent the progression of the disease, said Ms. Doyle. “Patients can achieve improvements in their blood sugar with a strategic program that includes diet, exercise, and nutritional supplementation to kick start their body into regulating the processing of insulin. Additionally, although addressing blood sugar management requires daily care, nutraceuticals are showing significant promise in boosting human health and preventing disease through their ability to fill in nutritional gaps.”
Effective Solutions
Many consumers today are looking for natural alternatives to prescription medications, said Mr. Majeed. “Proper nutrition plays a major role in healthy management of blood glucose levels as well as diabetes and related complications. Several time-tested natural ingredients are known to modulate blood glucose and manage diabetes with no adverse health consequences. Thus, nutraceuticals may be of great help to consumers to achieve their goals of managing this condition, in addition to their regime of a well-balanced diet, exercise, and regular monitoring of blood sugar levels. Because of their promising outcome in several clinical trials, various functional foods and dietary supplements are well-accepted by consumers”.
Oxidative stress has a major role in the pathogenesis of type 2 diabetes and associated complications, he added. “Curcuminoids (including curcumin, demethoxycurcumin, and bisdemethoxycurcumin), polyphenolic pigments present in turmeric (Curcuma longa), have been known to possess potent antioxidant properties. Sabinsa’s Curcumin C3 Complex is obtained from the dried rhizomes of Curcuma longa and standardized to 95% curcuminoids. In a recent randomized, placebo-controlled clinical study (Inflammopharmacology, 2016) 118 type 2 diabetic patients were given the combination of Curcumin C3 Complex (1,000 mg/day) and BioPerine (10 mg/day, as a bioavailability enhancer) for 8 weeks. Analysis of overnight fasting blood samples (at baseline and at the end of the study) suggested a significant improvement in total antioxidant capacity, SOD activity, and decreased malondialdehyde levels, a lipid peroxidation marker.
Mr. Majeed also noted that many traditional and Ayurvedic herbs have a long history of use for managing blood sugar, including Fenugreek (Trigonella foenum-graecum), cinnamon (Cinnamomum cassia), Pterocarpus marsupium, Gymnema sylvestre, Momordica charantia, common bean, kidney bean (Phaseolus vulgaris), Salacia reticulate, and Amla/Indian gooseberry (Emblica officinalis).
The path to diabetes involves daily actions that collectively impact the body’s capacity to maintain blood sugar within a healthy range, said Mr. Bérubé. “Sugar in many forms is found in our foods in record levels. Over a year, the average North American eats about 142 pounds of added sugar, which is quickly converted to glucose by our digestive enzymes.”
Interventional studies have shown that acting on dietary carbs before they reach the bloodstream as glucose is key in eliciting long-term health benefits, he added. “When comparing two glucose-reducing strategies in prediabetic individuals, one that acts before glucose reaches the bloodstream and another strategy that simply helps the body release more insulin, researchers noted marked reduction in cardiovascular events and progression to diabetes with the first strategy while helping to release additional insulin did not show any benefit. Fortunately, ingredients that have mechanisms of action suitable to act on dietary carbs before they get converted to glucose by digestive enzymes represent a new opportunity to attract consumers.”
InnoVactiv’s InSea2 has been shown in multiple human trials to reduce post-meal blood glucose and insulin levels, while improving insulin sensitivity, providing an effective relief against “glycemic stress,” said Mr. Bérubé. “InSea2 acts on alpha-amylase and alpha-glucosidase enzymes in the gut to reduce the speed at which these enzymes convert starch and sugar into glucose. It thus works immediately upon first use to bring several health benefits such as promoting optimal cognitive functioning after meal and optimizing blood glucose metabolism.”
Pharmachem’s Mr. Skop noted that the company’s Prenulin, a patented, proprietary blend of L-arabinose and chromium picolinate, has been shown in clinical studies to aid in reducing the body’s ability to absorb sugar, thereby lowering glucose and insulin impact by up to 30%. Two human clinical studies have shown that it safely lowered both circulating glucose and insulin levels after a 70-gram glucose challenge.
Phase 2 Carb Controller is an all-natural, non-stimulant, white kidney bean extract clinically shown to help delay the digestion and absorption of dietary starches by temporarily inhibiting salivary and pancreatic alpha-amylase. Carbohydrates that are resistant to digestion in the small intestine are delivered to the large intestine where they act more like dietary fiber, feeding the microbiota and upregulating GLP-1, which regulates satiety signaling. At the end of a 12-week weight-loss period, the supplement group lost more weight than those in the placebo group.
“Recently, there has been a shift toward the reduction of carbohydrate intake, particularly simple carbohydrates, as an approach to manage excess weight,” said Mr. Skop. “The digestion of carbohydrates begins with amylase secreted by the salivary glands. The alpha-amylase inhibitor properties of Phase 2 white kidney bean extract have been heavily studied with positive results in delaying the digestion and absorption of carbohydrates, thereby lowering their glycemic impact.”
Carbohydrates that are resistant to digestion in the small intestine are delivered to the large intestine where they act more like dietary fiber—feeding the microbiome and upregulating GLP-1.
Ms. Witwer noted that 100% fruit NuBana Green Banana Flour has high levels of RS2 resistant starch, making it an ideal product for blood sugar management. Green bananas are naturally rich in RS2 resistant starch; they are also rich in potassium, an essential mineral with important health benefits.
“Overwhelming clinical studies have shown that RS2 resistant starch significantly improves insulin sensitivity, most likely through the changed genetic expression in the intestinal tract.” Traditional diets included 30-50 grams of resistant starch/day, but resistant starch has been processed out of our diets. Modern diets include about 5 grams of resistant starch/day.
“Supplementing with NuBana Green Banana Flour is easy. Consumers can easily consume lower quantities for maintaining health or higher quantities needed for the full range of metabolic and insulin sensitivity benefits of resistant starch without consuming extra calories.”
In December, the U.S. FDA approved a qualified health claim that RS2 resistant starch from corn improves insulin sensitivity and reduces the risk of type 2 diabetes. “Two clinical studies have also shown that RS2 resistant starch from green bananas also improve insulin sensitivity in healthy people (Hoffmann Sarda, 2016) and in adults with type 2 diabetes (Ble-Castillo, 2010). The Hoffmann Sarda study surprisingly found improved insulin sensitivity in healthy adults consuming lower doses of RS2 resistant starch from green banana flour.”
A significant amount of scientific research has been conducted around the benefits of nutritional supplements, and many studies demonstrate that they might have a positive effect on reducing the risk of disease, according to Jim Komorowski, chief science officer, Nutrition 21. “In a recent report published by Frost & Sullivan, it was shown that taking specific nutritional supplements could not only help increase the prevention of specific diseases, such as diabetes, but it could also potentially provide significant individual and societal healthcare savings. The report found that ‘a cumulative 649,944 events from 2013 to 2020 could potentially be avoided if all U.S. diabetics over the age of 55 diagnosed with CHD were to use chromium picolinate dietary supplements at preventive intake levels.’”
Nutrition 21’s Chromax Chromium picolinate has been shown to lower elevated fasting blood sugar, lower insulin levels, and help insulin work better, he added. “Chromium (Cr) is a trace element which is essential for carbohydrate, lipid, and protein metabolism. Low chromium status can adversely affect blood glucose, insulin, total cholesterol, and triglycerides. Chromium is an insulin cofactor. It increases insulin-stimulated glucose metabolism by enhancing glucose transporter trafficking, enabling excess blood glucose to enter cells. This means that chromium helps insulin function more effectively.”
Ms. Doyle said two clinical studies done in healthy, adult populations confirm the blood sugar management benefits of OmniActive’s OmniLean. The CARBS (Carbohydrate, Appetite Reduction, Blood Sugar and Satiety) study, published in Nutrients, was a randomized, double-blind, placebo-controlled, cross-over study and the first to examine the effects of a proprietary extract of Salacia chinensis (from OmniLean) on glycemic indices and gut hormones after a meal. OmniLean, taken with a meal, resulted in an improved glycemic response and changes in gut hormones in healthy overweight/obese individuals, thereby reducing blood sugar spikes and impacting appetite and satiety.
BIG (Blood, Insulin and Glucose), published in the Journal of Diabetes Research, was a randomized, double-blind, placebo-controlled study involving 35 healthy individuals; researchers examined OmniLean’s impact on blood sugar and insulin after a high-carbohydrate load. The study showed OmniLean reduced the early rise in blood glucose and insulin following a high-sucrose (table sugar) load (slowdown of the post-prandial hyperglycemic process), helped support healthy carbohydrate/glucose and or insulin metabolism at a dose as small as 300 mg. “This was especially interesting considering studies in literature of Salacia reticulata, and Salacia oblongata found to be efficacious at 1,000 mg or higher doses,” said Ms. Doyle.
Ms. Eng said HP Ingredients offers Bergamonte bergamot, which contains bioactive flavonoids that are proven to help maintain healthy blood glucose levels, and healthy cholesterol profiles. “We have three recent studies showing a new mechanism of action of bergamot-derived polyphenolic fraction (Bergamonte BPF) bergamot. The three scientific investigations have uncovered Bergamonte BPFs ability to help millions of consumers to address metabolic syndrome and liver support—in particular non-alcoholic fatty liver disease, a condition that exacerbates unhealthy cholesterol levels, blood sugar insufficiency, and weight/fat accumulation.”
BENEO’s Mr. Peters said prevention strategies specifically targeted to people in a pre-diabetic state, at the onset of developing diabetes, are urgently needed. “The glycemic response of foods is what counts in this respect. BENEO’s functional fibers and carbohydrates are low glycemic ingredients that provide technical and physiological benefits in various applications. For example, oligofructose can help to lower the glycemic response of foods when replacing sugar partially in products. Many people look for sugar reduced products to support blood sugar management. However, whenever sugar is replaced by high glycemic ingredients like maltodextrin, there’s no beneficial effect with regard to blood glucose response. Therefore, finding the right products for blood sugar management can be a big challenge for consumers.”
BENEO’s Palatinose is a fully available yet low-glycemic carbohydrate that is slowly digested and absorbed, thus providing balanced and sustained energy with a lower blood glucose rise and less inulin release. ISOMALT has half the calories of beet sugar and offers a very low glycemic response, Mr. Peters said.
“Inulin and oligofructose are an additional option when looking to reduce the glucose supply of foods. They are both prebiotic fibers naturally derived from chicory root. Partially replacing high-glycemic sugars, these chicory fibers effectively reduce the glycemic response of foods.”
For the future, Pharmahem’s Mr. Skop noted that according to reports from the CDC, from 1999 through 2014, obesity prevalence increased among adults and youth. “Therefore, a challenge is marketing to younger adults, who likely have greater risk than ever of developing insufficient blood sugar response, having higher fasting blood sugar levels. This primarily all stems from high-sugar, high-carb diets. Diet (fitness) and blood sugar health go hand-in-hand. Younger adults still feel invincible, and don’t think too much about consequences to their health in later years from habits they indulge in today.”
Ms. Witwer noted that one third of American adults are currently prediabetic. “We do not know how many more American adults are insulin resistant but not yet prediabetic. This is a public health crisis and classifies as a worldwide epidemic. There is a tremendous opportunity for the nutraceuticals industry to help the nation address the crisis and help Americans maintain healthy blood sugar levels, for today and for years to come.”
Additionally, many consumers have prediabetes, a condition where blood sugar levels are higher than normal but not yet high enough to be type 2 diabetes. Without lifestyle changes through, people with prediabetes are likely to progress to type 2 diabetes.
Consumers face many challenges when it comes to managing these health conditions, as they require life-long commitments that often lead to physical and mental struggles, said Shaheen Majeed, worldwide president, Sabinsa, East Windsor, NJ. “The most common challenges faced by such patients include difficulty in maintaining healthy blood sugar levels given that they can fluctuate unexpectedly at times, failing to identify foods with high levels of sugar and carbohydrates, lack of physical exercise, etc.”
Blood sugar management is not easy for many consumers to understand, said Rhonda Witwer, vice president of marketing for start-up ingredient technology company International Agriculture Group (IAG). “It is not just about sugar or glucose in the blood (which doctors talk about and measure); it is really about how insulin controls blood sugar levels. This makes it more complicated for consumers. People do not generally talk about insulin. Doctors do not directly measure it and it has remained an invisible but critical part of our metabolism.”
Insulin sensitivity may degrade for 10-15 years before someone is diagnosed with type 2 diabetes, she continued. “Blood sugar is the last biomarker affected by the loss of blood sugar control. Insulin sensitivity is the first biomarker affected. We do not measure insulin sensitivity, however, so it remains invisible.”
Insulin resistance means that someone has higher than normal levels of insulin, especially after eating carbohydrate-rich foods. High levels of insulin trigger the body to store fat and prevent fat from being utilized as energy by the body, Ms. Witwer explained. “Thus, weight gain and/or an inability to lose weight may be an indication that someone is insulin resistant. For instance, some people are sensitive to carbohydrates and will easily gain weight after eating refined carbohydrate rich foods. This is likely due to the high insulin spike that occurs after the consumption of refined carbohydrates, which promotes fat storage. While the weight gain is commonly attributed to aging or getting older, it is more likely due to insulin resistance, a condition that can be changed.”
The Sins of Sugar
Sugar has become public enemy number one in terms of public health evaluation. Whereas fats were once vilified, leading to many low-fat formulations with higher sugar contents, research and public understanding has shifted.
The Lancet recently published results from the Prospective Urban Rural Epidemiology (PURE) study, in which researchers assessed dietary intake of 135,335 individuals aged 35–70 years (enrolled between Jan 1, 2003 and March 31, 2013) in 18 countries using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorized into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. Researchers assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality.
Results indicated that high carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. “Global dietary guidelines should be reconsidered in light of these findings,” researchers concluded.
“The PURE study results show that subjects eating high amounts of carbohydrates were 28% more at risk of total mortality than subjects in the lowest carb intake quintile,” noted Jocelyn Bérubé, executive & scientific director, Health & Nutrition, InnoVactiv Inc., Rimouski, Quebec, Canada. “Risks of major cardiovascular diseases increased sharply in subjects consuming more than 70% of their calories as carbohydrates (about one quarter of subjects were in that 70%-and-up range). Paradoxically, subjects eating the highest amounts of dietary fats (and of each type of fat) had lower odds of total mortality and non-cardiovascular mortality compared to subjects eating the lowest amount.”
For nearly half a century, the spotlight has been on fats when it comes to optimizing diet, he added. “As a result, an ever-increasing range of low-fat foods allowed people to indulge while giving them a clear conscience about their health. We now know that these low-fat foods were created by substituting fats with sugar and other types of carbohydrates, such as starch and dextrins. These sugars brought desirable attributes to foods that were lost when removing fats: taste and texture. As we cut the fat out of our lives, we paved a golden path for an ever-increasing intake of sugar. This study indicates that high dietary carbohydrate intake needs to be addressed to maintain health. The golden years of the low-fat trends should be a thing of the past.”
Poor glucose control and insulin resistance are two of the most pervasive biomarkers associated with chronic diseases affecting over 80% of Americans, according to Mitch Skop, senior director of new product development, Pharmachem Laboratories Inc., Kearny, NJ. “Insulin resistance occurs for a variety of reasons, but primarily it’s due to diets that tend to be abundant in starchy foods with high sugar content. Researchers have suggested that an important factor of this epidemic is the increased intake of simple carbohydrates that are rapidly absorbed (particularly sugars).”
Simple carbohydrates like sugar are quickly converted into glucose, he continued. “After eating, the pancreas detects this sudden rise in glucose and tries to regulate it by excreting insulin into the bloodstream. A rise in insulin signals the body to stop burning stored fat and begin to burn circulating glucose. Until glucose levels return to normal, the body is more efficient at storing fat than burning it.”
A sensible diet and exercise plan is the cornerstone of metabolic management, he said. “But if we can begin to safely impact the absorption of glucose, help insulin receptors work more efficiently, and at the same time increase the amount of resistant starch that gets delivered to the large intestine (to feed the microbiota and modulate the gut hormones responsible for appetite)—there is a better chance of staving off high blood sugar and the negative impacts it brings.”
Once high blood sugar sets in, the pancreas is stressed to produce and release exorbitant amounts of insulin to keep up, to shuttle the glucose to where it belongs, said Annie Eng, CEO, HP Ingredients, Bradenton, FL. “The challenges arise in the symptoms that dramatically impact quality of life: excessive thirst, excessive need to urinate, headaches and blurred vision, fatigue and trouble concentrating, and believe it or not, loss of weight. Once a diagnosis of superlatively high fasting blood glucose is given, the individual then must make significant lifestyle changes, giving rise to other mild to moderate challenges including higher stress and low mood.”
Lynda Doyle, senior vice president of global marketing, OmniActive Health Technologies, Morristown, NJ, said a lack of symptoms associated with high blood sugar presents a challenge to consumers. “Most people may be unaware that they have high blood sugar until their doctor tells them or after symptoms develop. Another big challenge is the increasing prevalence of overweight/obese individuals, which impacts blood sugar management. It’s estimated that almost half of the global population may be obese or overweight by 2030 (according to the Global Panel on Agriculture and Food Systems for Nutrition).”
Dietary intervention can also make management difficult since sugar is such a pervasive ingredient and not always readily apparent in foods, she added. “Consumers may find that avoiding sugar is too onerous and eventually give up. Finally, lack of exercise can impact blood sugar too—whether through its effect on weight gain or other mechanisms. Most likely, it is a combination of some or all of these factors that presents a challenge to consumers trying to manage their blood sugar that in many cases leads to non-compliance.”
Diet and lifestyle changes aimed at weight loss are known to be effective, but they are difficult to sustain over the long-term due to a compensatory increase in appetite and food intake, said Jon Peters, president, BENEO Inc., Parsippany, NJ. “As consumers become more sophisticated on how they approach their diets and nutritional choices, they expect food to contribute to their overall fitness. They will become increasingly interested in the role carbohydrates can play in terms of digestibility, caloric value, glycemic response, or the ability to influence the use of fat or glycogen storages.”
Opportunities & Challenges for Nutraceuticals
To be clear, diabetes is a life-threatening disease and by law, under the Dietary Supplement Health and Education Act (DSHEA), dietary supplements cannot make claims to mitigate, treat, cure, or prevent disease.
“We can, however, help healthy people reduce their risk of getting into trouble with their serum glucose with natural ingredients,” said Mr. Skop. “There are many hidden sugars in the foods we eat. Cooking from scratch—using whole, raw foods enhanced with natural culinary spices—is practiced by very few Americans.”
Many products claim to help manage healthy blood sugar levels. However, product developers face several challenges, according to Sabinsa’s Mr. Majeed, including selecting proper ingredients that are safe and backed by science-based claims, finalizing optimally effective dosages as well as end-product format (e.g., nutrition bar, shake, capsule/tablet).
“Another major issue is to deal with adulteration, or substitution of original natural actives with spurious or look-alike substandard ingredients,” he added. “And this can be addressed by carrying out proper tests before including such ingredients into the intended formulation, and carefully sourcing only from suppliers with an established track record.”
According to Bill Levi, vice president of operations, Nutrition 21, Purchase, NY, the two largest issues that product developers are facing with respect to the blood sugar management market revolve around specific demographics of patients as well as the reluctance of the medical community to recommend natural alternatives to treatment. “Patients who have blood glucose management issues have typically led a sedentary lifestyle combined with poor dietary choices. They aren’t as educated on what natural products exist on the market to help with their condition. They rely heavily on the opinions and recommendations of their physicians, rarely venturing out on their own to find non-pharmaceutical supplemental solutions. Additionally, the medical community is hesitant to recommend natural supplements over pharmaceuticals to patients as a treatment option for the management of their condition. This leads patients to be much more hesitant when it comes to purchasing or even considering any form of natural supplement or nutraceutical.”
Historically, people looking for blood sugar supplements were encouraged to do so because of family history of diabetes, or because they were overweight and concerned about their higher risk of long-term blood glucose issues, said Mr. Bérubé. “One of the challenges we face in attracting new consumers to this market is that undesired blood glucose levels do not necessarily generate symptoms, and when they do these symptoms are being wrongly associated with other conditions.”
For example, many people may feel a drop in mental energy after large meals. “Popular belief is that after a meal, our digestive tract requires an increasing blood flow to support its digestive efforts, which in turn deprives our brain of much needed energy. This myth has been proven wrong many times, with studies showing that brain blood flow is always prioritized over other organs, even during high-intensity physical exercise. Very few people actually know that blood glucose swings are responsible for these transient ‘food comas,’ and that more control over blood glucose after meals can actually help sustain optimal cognitive function throughout the day.”
Traditionally, blood sugar management has been linked to a disease state, such as diabetes which has been a challenge for supplement manufacturers that are looking to formulate a viable product, said Ms. Doyle. “However, with the rise in popularity of no/low-carb and paleo diets, consumer interest has been piqued and awareness of the health benefits of maintaining healthy blood sugar for not only weight management but for overall health and well-being has become mainstream. This has the market poised to break into new, exciting opportunities with expanded demographics and novel deliveries. For instance, OmniLean (the company’s proprietary extract of Salacia chinensis) has tremendous promise because of its formulation flexibility which includes tablets and capsules, as well as functional foods and beverages.”
Although historically, individuals with blood glucose issues were unaware or uninformed about the benefits of adding a nutraceutical into their daily regimen, more recently, consumers have been more inclined to educate themselves on what to look for in specific nutritional supplements, she added. “Additionally, over time, there has been some turn over in the traditional medical community allowing for an upsurge of homeopathic or more naturally inclined physicians, who are open to exploring nutraceuticals as a recommended option for their patients.”
Keeping weight in check and being physically active can help prevent many cases of diabetes, however, because a balanced diet contributes to the body’s glycemic control, it can also help to prevent the progression of the disease, said Ms. Doyle. “Patients can achieve improvements in their blood sugar with a strategic program that includes diet, exercise, and nutritional supplementation to kick start their body into regulating the processing of insulin. Additionally, although addressing blood sugar management requires daily care, nutraceuticals are showing significant promise in boosting human health and preventing disease through their ability to fill in nutritional gaps.”
Effective Solutions
Many consumers today are looking for natural alternatives to prescription medications, said Mr. Majeed. “Proper nutrition plays a major role in healthy management of blood glucose levels as well as diabetes and related complications. Several time-tested natural ingredients are known to modulate blood glucose and manage diabetes with no adverse health consequences. Thus, nutraceuticals may be of great help to consumers to achieve their goals of managing this condition, in addition to their regime of a well-balanced diet, exercise, and regular monitoring of blood sugar levels. Because of their promising outcome in several clinical trials, various functional foods and dietary supplements are well-accepted by consumers”.
Oxidative stress has a major role in the pathogenesis of type 2 diabetes and associated complications, he added. “Curcuminoids (including curcumin, demethoxycurcumin, and bisdemethoxycurcumin), polyphenolic pigments present in turmeric (Curcuma longa), have been known to possess potent antioxidant properties. Sabinsa’s Curcumin C3 Complex is obtained from the dried rhizomes of Curcuma longa and standardized to 95% curcuminoids. In a recent randomized, placebo-controlled clinical study (Inflammopharmacology, 2016) 118 type 2 diabetic patients were given the combination of Curcumin C3 Complex (1,000 mg/day) and BioPerine (10 mg/day, as a bioavailability enhancer) for 8 weeks. Analysis of overnight fasting blood samples (at baseline and at the end of the study) suggested a significant improvement in total antioxidant capacity, SOD activity, and decreased malondialdehyde levels, a lipid peroxidation marker.
Mr. Majeed also noted that many traditional and Ayurvedic herbs have a long history of use for managing blood sugar, including Fenugreek (Trigonella foenum-graecum), cinnamon (Cinnamomum cassia), Pterocarpus marsupium, Gymnema sylvestre, Momordica charantia, common bean, kidney bean (Phaseolus vulgaris), Salacia reticulate, and Amla/Indian gooseberry (Emblica officinalis).
The path to diabetes involves daily actions that collectively impact the body’s capacity to maintain blood sugar within a healthy range, said Mr. Bérubé. “Sugar in many forms is found in our foods in record levels. Over a year, the average North American eats about 142 pounds of added sugar, which is quickly converted to glucose by our digestive enzymes.”
Interventional studies have shown that acting on dietary carbs before they reach the bloodstream as glucose is key in eliciting long-term health benefits, he added. “When comparing two glucose-reducing strategies in prediabetic individuals, one that acts before glucose reaches the bloodstream and another strategy that simply helps the body release more insulin, researchers noted marked reduction in cardiovascular events and progression to diabetes with the first strategy while helping to release additional insulin did not show any benefit. Fortunately, ingredients that have mechanisms of action suitable to act on dietary carbs before they get converted to glucose by digestive enzymes represent a new opportunity to attract consumers.”
InnoVactiv’s InSea2 has been shown in multiple human trials to reduce post-meal blood glucose and insulin levels, while improving insulin sensitivity, providing an effective relief against “glycemic stress,” said Mr. Bérubé. “InSea2 acts on alpha-amylase and alpha-glucosidase enzymes in the gut to reduce the speed at which these enzymes convert starch and sugar into glucose. It thus works immediately upon first use to bring several health benefits such as promoting optimal cognitive functioning after meal and optimizing blood glucose metabolism.”
Pharmachem’s Mr. Skop noted that the company’s Prenulin, a patented, proprietary blend of L-arabinose and chromium picolinate, has been shown in clinical studies to aid in reducing the body’s ability to absorb sugar, thereby lowering glucose and insulin impact by up to 30%. Two human clinical studies have shown that it safely lowered both circulating glucose and insulin levels after a 70-gram glucose challenge.
Phase 2 Carb Controller is an all-natural, non-stimulant, white kidney bean extract clinically shown to help delay the digestion and absorption of dietary starches by temporarily inhibiting salivary and pancreatic alpha-amylase. Carbohydrates that are resistant to digestion in the small intestine are delivered to the large intestine where they act more like dietary fiber, feeding the microbiota and upregulating GLP-1, which regulates satiety signaling. At the end of a 12-week weight-loss period, the supplement group lost more weight than those in the placebo group.
“Recently, there has been a shift toward the reduction of carbohydrate intake, particularly simple carbohydrates, as an approach to manage excess weight,” said Mr. Skop. “The digestion of carbohydrates begins with amylase secreted by the salivary glands. The alpha-amylase inhibitor properties of Phase 2 white kidney bean extract have been heavily studied with positive results in delaying the digestion and absorption of carbohydrates, thereby lowering their glycemic impact.”
Carbohydrates that are resistant to digestion in the small intestine are delivered to the large intestine where they act more like dietary fiber—feeding the microbiome and upregulating GLP-1.
Ms. Witwer noted that 100% fruit NuBana Green Banana Flour has high levels of RS2 resistant starch, making it an ideal product for blood sugar management. Green bananas are naturally rich in RS2 resistant starch; they are also rich in potassium, an essential mineral with important health benefits.
“Overwhelming clinical studies have shown that RS2 resistant starch significantly improves insulin sensitivity, most likely through the changed genetic expression in the intestinal tract.” Traditional diets included 30-50 grams of resistant starch/day, but resistant starch has been processed out of our diets. Modern diets include about 5 grams of resistant starch/day.
“Supplementing with NuBana Green Banana Flour is easy. Consumers can easily consume lower quantities for maintaining health or higher quantities needed for the full range of metabolic and insulin sensitivity benefits of resistant starch without consuming extra calories.”
In December, the U.S. FDA approved a qualified health claim that RS2 resistant starch from corn improves insulin sensitivity and reduces the risk of type 2 diabetes. “Two clinical studies have also shown that RS2 resistant starch from green bananas also improve insulin sensitivity in healthy people (Hoffmann Sarda, 2016) and in adults with type 2 diabetes (Ble-Castillo, 2010). The Hoffmann Sarda study surprisingly found improved insulin sensitivity in healthy adults consuming lower doses of RS2 resistant starch from green banana flour.”
A significant amount of scientific research has been conducted around the benefits of nutritional supplements, and many studies demonstrate that they might have a positive effect on reducing the risk of disease, according to Jim Komorowski, chief science officer, Nutrition 21. “In a recent report published by Frost & Sullivan, it was shown that taking specific nutritional supplements could not only help increase the prevention of specific diseases, such as diabetes, but it could also potentially provide significant individual and societal healthcare savings. The report found that ‘a cumulative 649,944 events from 2013 to 2020 could potentially be avoided if all U.S. diabetics over the age of 55 diagnosed with CHD were to use chromium picolinate dietary supplements at preventive intake levels.’”
Nutrition 21’s Chromax Chromium picolinate has been shown to lower elevated fasting blood sugar, lower insulin levels, and help insulin work better, he added. “Chromium (Cr) is a trace element which is essential for carbohydrate, lipid, and protein metabolism. Low chromium status can adversely affect blood glucose, insulin, total cholesterol, and triglycerides. Chromium is an insulin cofactor. It increases insulin-stimulated glucose metabolism by enhancing glucose transporter trafficking, enabling excess blood glucose to enter cells. This means that chromium helps insulin function more effectively.”
Ms. Doyle said two clinical studies done in healthy, adult populations confirm the blood sugar management benefits of OmniActive’s OmniLean. The CARBS (Carbohydrate, Appetite Reduction, Blood Sugar and Satiety) study, published in Nutrients, was a randomized, double-blind, placebo-controlled, cross-over study and the first to examine the effects of a proprietary extract of Salacia chinensis (from OmniLean) on glycemic indices and gut hormones after a meal. OmniLean, taken with a meal, resulted in an improved glycemic response and changes in gut hormones in healthy overweight/obese individuals, thereby reducing blood sugar spikes and impacting appetite and satiety.
BIG (Blood, Insulin and Glucose), published in the Journal of Diabetes Research, was a randomized, double-blind, placebo-controlled study involving 35 healthy individuals; researchers examined OmniLean’s impact on blood sugar and insulin after a high-carbohydrate load. The study showed OmniLean reduced the early rise in blood glucose and insulin following a high-sucrose (table sugar) load (slowdown of the post-prandial hyperglycemic process), helped support healthy carbohydrate/glucose and or insulin metabolism at a dose as small as 300 mg. “This was especially interesting considering studies in literature of Salacia reticulata, and Salacia oblongata found to be efficacious at 1,000 mg or higher doses,” said Ms. Doyle.
Ms. Eng said HP Ingredients offers Bergamonte bergamot, which contains bioactive flavonoids that are proven to help maintain healthy blood glucose levels, and healthy cholesterol profiles. “We have three recent studies showing a new mechanism of action of bergamot-derived polyphenolic fraction (Bergamonte BPF) bergamot. The three scientific investigations have uncovered Bergamonte BPFs ability to help millions of consumers to address metabolic syndrome and liver support—in particular non-alcoholic fatty liver disease, a condition that exacerbates unhealthy cholesterol levels, blood sugar insufficiency, and weight/fat accumulation.”
BENEO’s Mr. Peters said prevention strategies specifically targeted to people in a pre-diabetic state, at the onset of developing diabetes, are urgently needed. “The glycemic response of foods is what counts in this respect. BENEO’s functional fibers and carbohydrates are low glycemic ingredients that provide technical and physiological benefits in various applications. For example, oligofructose can help to lower the glycemic response of foods when replacing sugar partially in products. Many people look for sugar reduced products to support blood sugar management. However, whenever sugar is replaced by high glycemic ingredients like maltodextrin, there’s no beneficial effect with regard to blood glucose response. Therefore, finding the right products for blood sugar management can be a big challenge for consumers.”
BENEO’s Palatinose is a fully available yet low-glycemic carbohydrate that is slowly digested and absorbed, thus providing balanced and sustained energy with a lower blood glucose rise and less inulin release. ISOMALT has half the calories of beet sugar and offers a very low glycemic response, Mr. Peters said.
“Inulin and oligofructose are an additional option when looking to reduce the glucose supply of foods. They are both prebiotic fibers naturally derived from chicory root. Partially replacing high-glycemic sugars, these chicory fibers effectively reduce the glycemic response of foods.”
For the future, Pharmahem’s Mr. Skop noted that according to reports from the CDC, from 1999 through 2014, obesity prevalence increased among adults and youth. “Therefore, a challenge is marketing to younger adults, who likely have greater risk than ever of developing insufficient blood sugar response, having higher fasting blood sugar levels. This primarily all stems from high-sugar, high-carb diets. Diet (fitness) and blood sugar health go hand-in-hand. Younger adults still feel invincible, and don’t think too much about consequences to their health in later years from habits they indulge in today.”
Ms. Witwer noted that one third of American adults are currently prediabetic. “We do not know how many more American adults are insulin resistant but not yet prediabetic. This is a public health crisis and classifies as a worldwide epidemic. There is a tremendous opportunity for the nutraceuticals industry to help the nation address the crisis and help Americans maintain healthy blood sugar levels, for today and for years to come.”
