Grasping Metabolic Syndrome

All diseases have risk factors, but possibly none borrows all of its defining risk factors from other high-profile diseases more so than metabolic syndrome. Obesity, heart disease and diabetes all contribute top factors to metabolic syndrome, which is still clamoring for space in the minds of health professionals and consumers. While this syndrome hasno specific treatment , there are a number of natural products help address each risk factor involved.

"Metabolic syndrome is a cluster of adverse features including abdominal obesity, hypertension, dyslipidemia and insulin resistance that are linked to an increased chance of cardiovascular diseases and diabetes," explained Sharon Ling, Ph.D., vice president of scientific affairs for Carotech (UK).

According to the American Heart Association (AHA), five main markers determine metabolic syndrome, also known as syndrome X. It only takes the presence of three of these five markers to generate a diagnosis of metabolic syndrome:

The rapid increase in metabolic syndrome in Western societies raised this issue higher on the public health watch list, according to Equinox Group, which consults for pharmaceutical and biotechnology companies. In a recent report, the group cited national U.S. data suggesting metabolic syndrome afflicts about one-quarter of adults aged 20 to 70, with about half of the elderly suffering the condition. More importantly, Equinox points out no specific therapy for metabolic syndrome exists, but approaches focus on the individual primary components, such as insulin resistance, pre-diabetes, hyper/dyslipidemia and hypertension. The report further states while a few well-established drugs offer mechanisms that could benefit the numerous risk factors, each has its shortcomings, and "few pharmacological options currently exist for treating what is the underlying condition in the majority of metabolic syndrome casesoverweight and obesity."

The market for metabolic syndrome is similarly difficult to define, because it overlaps so many other well-established market segments, including cardiovascular health, diabetes and weight management. One way to gauge the market opportunity is to look at the markets for some of the major risk factors, including cholesterol and blood pressure (cardiovascular), blood sugar (diabetes), weight management and inflammation.

Windrose Partners reported the global health wellness market is about $600 billion, with the U.S. market at about $153 billion; nearly$4 billion of health and wellness foods and beverages targeted cardiovascular health, and the future outlook is for growth. SPINS noted during the 12 months from October 2009 to October 2010, consumers in natural food stores (excluding Whole Foods Market) bought $227 million worth of supplements marketed for benefits to hypertension, atherosclerosis and high cholesterol.

According to Windrose, new food, drink and dietary supplements product launches in the heart health category have tripled in the last five years and currently account for 1.5 percent of all new launches. Further, they noted heart health ingredients have logged an impressive $563 million revenue growth in the wholesale market in 2008 and are expected to eclipse $1 billion by 2012, which would be a compound annual growth rate (CAGR) of 20 percent.

The story is even more dramatic in the diabetes segment. The Centers for Disease Control and prevention (CDC) recently warned obesity and diabetes rates are at a 10-year high in the United States, with older Americans more likely to suffer these health issues. Elizabeth Sloan, Ph.D., president, Sloan Trends & Solutions Inc., reported the older generation (older than 55 years), which is commonly adverse to functional foods, is increasingly tuning into multifunctional supplements, such as for the multifactorial diabetes. She also pinned pre-diabetes as a growing condition trend for this same age group.

Steve French, managing partner at the Natural Marketing Institute (NMI), noted consumers are increasingly looking for foods that have reduced amounts of sugar, sodium, calories, fat, gluten and glycemic load (carbohydrates). He added cardiovascular health is a top claim sought by consumers, as is weight management, with diabetes and metabolic syndrome both growing in demand.

Beyond avoiding unhealthy ingredients, people with some level of diabetes could do well to seek out certain nutrients shown to help them mange their health. Research from Russell Jaffe, M.D., senior fellow at the Natural Health Research Institute (NHRI), and his team revealed diabetes patients who supplement with antioxidants such as ascorbates, polyphenolics and carotenoids; vitamins E, B and D3; minerals; carnitine; choline; omega-3 essential fatty acids (EFAs); prebiotics and probiotics; and coenzyme Q10 (CoQ10) could reduce medical care costs by 75 percent to 95 percent, saving as much as $130 billion each year. In fact, Jaffe explained if people being treated for type 2 diabetes were to use such nutrients for six months, they could decrease their fasting glucose scores by 20 percent, based on the research. In the study, patients taking supplements also reduced their insulin fasting scores by 18 percent, compared to a 12-percent decrease among control subjects.

"Because of the dramatic increase in type 2 diabetes, there is great consumer awareness of the disease state. However, we dont think most consumers understand the term metabolic syndrome, said Mitch Skop, senior director of new product development, Pharmachem Laboratories Inc.  "From that standpoint the market is still in its infancy." He suggested much more work needs to be done to help consumers make the connection between being overweight, having elevated blood pressure and fasting plasma glucose levels and the likelihood of developing diabetes. "This will allow manufacturers to develop supplements that address these issues and educate the consumer of their benefits," he said. "Consumers need to learn what this condition iswithout heavy or complicated scientific proseand how they can take steps to decrease their risk; at the same time, there cannot be a 'one pill fits all' approach here." Instead, he suggested a successful leading manufacturer in this segment will create a packaged system, an easy one-two-three approach, which includes emphasis and education about healthy lifestyle changes.

"The misconception among consumers is that people who are overweight will never develop metabolic syndrome, as they could diet at any time and then therefore subdue this danger," Schonalau noted. "Diabetes, in contrast, is diagnosed by the doctor and theres no arguing about it."Obesity, which factors in many health conditions including heart health, diabetes and metabolic syndrome, is a huge target. Euromonitor International sized the global weight management market at around $144 billion (2010) and said it could grow to around $162 billion (2015). The bulk of diet sales are reduced-calorie products, according to the firm, followed by meal replacement products. The firm said the United States is one of the leaders of fortified weight management products. Functional products, it noted, face challenges related to safety and lavish claims.

Domestically, the meal replacement industry saw revenues increase an average of 6.9 percent per year between 2006 and 2011, according to a new report from IBISWorld. The firm said revenues in 2011 alone will grow 9.3 percent to $2.2 billion. Profit margins of about 4.9 percent and consistently increasing revenue will make this segment attractive to new entrants, the firm concluded.

For supplements, Nutrition Business Journal has reported sports nutrition and weight-loss products, including supplements and meal replacements, has regained momentum after struggling in 2009. The category posted 9-percent annual growth in 2010, on the strength of $2 billion in new sales and $22.7 billion in total sales.

Ingredient Drivers

Improving the diet is an important first step. Known as effective in heart health, the Mediterranean diet has shown its merits against metabolic syndrome. A 2011 review involving 50 studies and half a million subjects found adherence to the diet reduced the risk of metabolic syndrome.¹ Researchers from Harokopio University of Athens, Greece, concluded the diet has positive effects on markers of metabolic syndrome and lowers both the prevalence and progression of the syndrome; they noted essential fatty acids (EFAs) found in olive oil, a staple of the diet, address inflammation, one of the syndrome's main risk factors.

While the diet can help lower risk, adding a low-glycemic meal replacement can help turn back the syndrome, according to recent study results. A multicenter clinical trial found UltraMeal® PLUS 360° (from Metagenics), which was designed to target metabolic syndrome and cardiovascular health, reduced heart disease more than the diet alone.² Researchers also found the meal replacement was 40-percent more likely to resolve metabolic syndrome.

The Mediterranean diet is often praised for its low-fat dairy component. However, 2010 research has indicated a compound in dairy might help improve several of the risk factors that define metabolic syndrome.³ Multivariate analyses of data from a cohort of 3,736 adults participating in a cardiovascular health trial showed whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels, which were then associated with slightly lower adiposity and, independently, with higher HDL levels, lower triglyceride levels, a lower total cholesterol-to-HDL ratio, lower C-reactive protein (CRP) levels and lower insulin resistance. Results also linked trans-palmitoleate to substantially lower incidence of diabetes. Protective associations with metabolic risk factors were confirmed in an independent cohort of 327 women.

Sometimes good health simply requires the basics, and cardiovascular factors central to metabolic syndrome can be addressed with basic nutrients, such as vitamin E. Recent studies have shown Tocomin® natural palm mixed tocotrienols complex (from Carotech Inc.) has favorable effects on metabolic syndrome. Recent studies have shown tocotrienols convey favorable effects on metabolic syndrome, including normalizing blood pressure, improving lipid profiles, reversing atherosclerosis, reducing arterial stiffness, decreasing blood glucose, reversing fatty liver disease, reducing inflammation and inhibiting adipogenesis.

Tocotrienols can reverse non-alcoholic fatty liver disease (NAFLD), which Ling explained is considered the hepatic manifestation of the metabolic syndrome and is commonly associated with components of metabolic syndrome including obesity (60 percent to 95 percent), insulin resistance (28 percent to 55 percent), and hyperlipidemia (27 percent to 92 percent). The results of a interventional, double blind, placebo-controlled trial showed half of subjects taking Tocomin SupraBio® (from Carotech) for one year had complete remission, compared with only 23 percent in the control group; researchers suggested the tocotrienol supplement's antioxidant actions may be key to the benefits.⁴

Based on research, taking tocotrienols can help lower cholesterol as or more effectively than some statin medication.⁵ Supplementation for as few as two months may also reduced arterial stiffness, which is an independent risk factor of cardiovascular diseases (CVDs) and hypertension.⁶ According to a human study, two months of tocotrienol supplementation also appears to significantly lower systolic blood pressure, an effect also credited to antioxidant properties.⁷

Other nutrients shown to counter hypertension and manage blood pressure include the minerals calcium, magnesium and potassium; vitamins C and D; fish oil and omega-3 fatty acids; vasodilators L-arginine, French maritime pine bark and Ginkgo biloba; and other botanicals such as grape seed, olive leaf and aged- garlic extract.

In one study, 200 mg of pine bark extract (as Pycnogenol, from Horphag) lowered systolic blood pressure, but not diastolic;⁸ another study showed 100 mg/d of Pycnogenol improved endothelial function, decreased endothelin-1 concentrations and increased nitric oxide (NO) levels in plasma in patients with hypertension.⁹

Pycnogenol was initially investigated in clinical trials with type II diabetes patients. " When it was discovered that Pycnogenol® potently slows down digestion of complex carbohydrates, such as starch, it became apparent that the ideal role for this product is for pre-diabetic conditions and metabolic syndrome," explained Frank Schonlau, scientific director at Horphag Research and Natural Health Science. "Recent studies have shown that Pycnogenol is an all encompassing product for people affected by metabolic syndrome, as it tackles essentially all of the critical parameters: elevated blood pressure, cholesterol problems, high blood sugar and abdominal fat."

Proanthocyanidin flavanoids in Pycnogenol are often credited with its health benefits. These polyphenolic compounds are also found in grape seeds. In subjects with pre-hypertension, 300 g/d grape seed extract (GSE) lowered both systolic and diastolic blood pressure after two months, with no changes to serum lipids or glucose.¹⁰ Similar results were achieved in another trial on people with metabolic syndrome.¹¹

Grapes also contain resveratrol, which has reduced blood pressure, metabolic disturbances and inflammation in obese subjects.¹² In 2011, University of Alberta researchers reported resveratrol can help curtail long-term development of metabolic syndrome if administered early enough in the cycle.¹³ In a trial in obese men, resveratrol (as resVida, from DSM Nutritional Products) improved  circulating glucose, triglycerides, inflammation markers and systolic blood pressure, in addition to decreasing post-prandial plasma fatty acid, glycerol, and adipose tissue lipolysis.¹⁴  A resveratrol-like compound also found in grapes and other berries, pterostilbene acts as a PPAR-alpha agonist, which affects fatty acid and lipid catabolism, and can thereby decrease triglyceride synthesis and lower LDL and very LDL (vLDL) levels.¹⁵

Lipid improvements in metabolic syndrome is also a benefit of omega-3s in fish oil, which are also  crucial compounds in the inflammatory cascade. Research found a fish oil diet in metabolic syndrome subjects can lead to a significant reduction in blood pressure, serum insulin, triacylglycerols, cholesterol, free fatty acids and total lipids.¹⁶ A 2010 trial on 117 people with metabolic syndrome showed 12 weeks of either a diet rich in monounsaturated fats or supplemented with omega-3 fish oil resulted in lower triglycerides, compared to either a high-saturated fat diet, or one that is low-fat and high-carb.¹⁷

What's good from the fish is good from the cactus? Leaves from the Opuntia ficus-indica cactus, also known as prickly pear cactus, contain a lipophilic fiber that has improved lipid levels in overweight and obese people diagnosed with metabolic syndrome. In a randomized, placebo-controlled, double blind study conducted on 68 females with a body mass index (BMI) between 25 and 40, almost 40 percent of those taking 1.6 g of prickly pear fiber (as NeOpuntia®, from BioSerae) with meals no longer had metabolic syndrome.¹⁸ The supplement also increased HDL cholesterol levels and decreased triglycerides. NeOpuntia also demonstrated some potential as a fat blocker, suggesting a complementary weight management benefit in metabolic syndrome.

From the succulent plant Caralluma fimbriata, Slimaluma (from Gencro Pacific) targets the obesity and lipid factors that can contribute to development and progression of metabolic syndrome. Animal research showed Slimaluma can inhibit the progression and viability of preadipocytes.¹⁹ A 2010 in vitro study report detailed how Slimaluma given to animals also on a cafeteria-fed diet exerted antiobesity effects, possibly through hunger hormone management, and also demonstrated antiatherogenic effects, via influence of lipid parameters with antioixdant and anti-inflammatory effects.²⁰ In a human study, 50 adult men and women (25 to 60 years) with a body mass index (BMI) greater than 25 kg/m2 were randomly assigned to receive either  1 g/d of Caralluma extract or placebo for 60 days.²¹ Researchers assessed blood glucose and lipids, anthropometric measurements, dietary intake and appetite at the end of 30 and 60 days of intervention.  They found supplementation with this extract appears to suppress appetite, and reduce waist circumference when compared to placebo over a two-month period.Back in the ocean, polyphenols from brown seaweed offer carb-blocking properties. In a Canadian study, seaweed polyphenols (as InSea2, from innoVactiv) altered acute glycemic and insulin response to carb ingestion, resulting in reduced plasma glucose concentration, reduced insulin and increased insulin sensitivity.²²

An extract of white bean (Phaseolus vulgaris) is another a carb blocker and may also reduce blood glucose levels.²³ In one study, 445 mg/d of P. vulgaris extract (Phase 2 Carb Controller from Pharmachem Labs) significantly decreased bodyweight and waist size after one month of supplementation, owing to inhibiting carb absorption.²⁴ In his review of clinical studies on P. vulgaris extract, Jay Udani, M.D., CEO of Medicus Research, noted 500 mg/d to 3,000 mg/d, in either a single dose or in divided doses, can spark weight loss and reduced post-prandial spikes in blood glucose.²⁵ Phase 2 Carb Controller, which contains the vegetable-based satiety ingredient Olibra, is designed to offer additional potential beenfits to other aspects of metabolic syndrome when used in conjunction with   Phase 3 Sugar Controller, which focuses on blood glucose. Skop  noted a recent human study showed that Phase 3 had a significant effect on improving blood sugar and insulin levels after consumption of a beverage containing 70g of sugar.

"Man may be the captain of his fate, but he is also the victim of his blood sugar," quipped Wilfrid Oakley, an English physician and pioneer in clinical care of diabetes.

Found alongside sugar in many foods, cinnamon actually helps lower blood glucose, but only when taken in a sufficient enough dose. This can be achieved with supplementation. For instance, supplementation with 250 mg of an aqueous extract of cinnamon (as Cinnulin PF, from Integrity Nutraceuticals) administered two times per day for 12 weeks in 24 subjects with impaired fasting glucose resulted in increased antioxidant protection and improved insulin sensitivty.²⁶ In another study, 22 subjects with pre-diabetes and metabolic syndrome took 500 mg Cinnulin PF twice daily and subsequently experienced statistically significant decreases in fasting blood glucose, body fat and systolic blood pressure.²⁷

From bark to leaves, another ingredient for blood sugar management comes from the leaves of Lagerstroemia speciosa or banaba. Subjects in a 2003 study who received daily oral dosages of 32 and 48 mg of banaba extract (as Glucofit, from Soft Gel Technologies) for two weeks experienced a significant reduction in blood glucose levels.²⁸ Other research showed taking a softgel capsule of Glucofit after ingestion of a starchy meal improved both BMI and weight-loss.²⁹

While numerous other botanical ingredients including pine bark extract, Pterocarpus marsupium bark and heartwood extract, chia seeds, maitake mushroom and the Ayurvedic herbs Coccinia cordifolia and Trigonella foenum-graecum (fenugreek)have demonstrated blood glucose and insulin management benefits in research., several minerals also have important roles in glucose metabolism and could be useful in metabolic syndrome.

According to research, people with poorly managed diabetes taking 600 mcg/d chromium picolinate (as Chromax®, from Nutrition 21) combined with 10 mg/d biotin had significantly reduced fasting glucose, compared to placebo subjects.³⁰ Chromax can also help address hyperglycemia and cholesterolemia.³¹ Niacin-bound chromium (as ChromeMate®, from InterHealth) in similarly high doses was not only showed safe in obese women, but boosted the effect of exercise on rick factors for coronary artery disease (CAD).³²

Manganese is another beneficial mineral for blood glucose and metabolic syndrome management. In one trial, three weeks of administration of manganese and carob juice-derived D-chiro-inositol (as Chirositol, from Cyvex Nutrition) significantly reduced blood glucose levels in diabetic mellitus-induced rats.³³ Blood glucose levels decreased by a combined 23-percent after 12 days of Chirositol, compared to the control group; also, Chirositol and manganese sulfate resulted in a combined 40-percent decrease during the same time period. Researchers noted a decrease in overall body weight of both male and female rats receiving Chirositol and manganese sulfate, with females exhibiting a 25-percent body weight decrease over the control group; males has a 21-percent bodyweight decrease.

There are so many angles to approach metabolic syndrome, making it difficult to both define the market and deliver the specific benefits message. Shonlau advised addressing metabolic syndrome effectively requires a strong commitment to completely change to a healthier lifestyle, and simply taking supplements is not enough. "It requires physical exercise and a strong and lasting will to control calorie intake," he said.  

Most of the ingredients studied to improve the primary risk factors of metabolic syndrome have already been studied and marketed in other health conditions such as heart health, diabetes and inflammatory control. This leaves the metabolic syndrome segment with a challenge of generating research for the segment's own population, and carving out opportunities in the overlap of all the well-established markets for those related conditions.

Editors Note: INSIDERs Market Insight section is designed to give a broad overview of marketing and sales trends in a particular category.

References are on the next page...

References for Grasping Metabolic Syndrome

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