Metabolic syndrome: natural solutions for a worldwide health problem

Jack ChallemSymptoms of metabolic syndrome, a form of prediabetes, can be offset with natural compounds. But their effectiveness ultimately may depend on how these ingredients are combined in formulas. Jack Challem investigates

Ten years ago relatively few people appreciated the term 'metabolic syndrome.' Today, doctors around the world routinely diagnose it in patients, and the term is quickly becoming household words. The condition, a form of prediabetes, is also attracting the interest of natural-ingredients suppliers and supplements companies.

Prediabetes, of course, is a stepping stone to full-blown type 2 diabetes. The diagnosis of metabolic syndrome is based on a cluster of familiar symptoms that increase the risk of full-blown type 2 diabetes, coronary artery disease and many other disease processes. Metabolic syndrome is also known as Syndrome X and insulin resistance syndrome.

The official medical definitions of metabolic syndrome vary slightly among medical organisations, such as the US National Institutes of Health, the International Diabetes Federation and the World Health Organization.1,2,3 As a general rule, metabolic syndrome includes at least three of the following symptoms: insulin resistance; elevated blood glucose; abdominal obesity; hypertension; and elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglyceride in combination with decreased high-density lipoprotein (HDL) cholesterol.4

Insulin resistance, indicated by hyperinsulinaemia, forms the central feature of metabolic syndrome. It develops after years of eating high-glycaemic foods, which spike blood glucose levels and stimulate insulin secretion. As fasting and postprandial insulin levels increase, the body's cells become resistant to insulin's normal role in removing glucose from the blood. Glucose levels then climb, while insulin's collateral effects mount.

Because insulin promotes the storage of fat, particularly around the belly, abdominal obesity usually becomes the most visible sign of insulin resistance. Indeed, being overweight is the principal risk factor for developing prediabetes and diabetes. In the United States, two thirds of American adults are now overweight, with one third of Americans being obese (30 or more pounds over their ideal weight). Men fare a little worse than women, with four of every five American men now overweight.5

In England, 39 per cent of people are overweight and 21 per cent are obese. The numbers are rising, and projections indicate that one third of British men will be obese by 2010.6 Regardless of what you might have heard about French women not getting fat, 42 per cent of French citizens tip the scales as overweight or obese, and the per cent goes up to 51 per cent in some parts of the country.7

Hyperinsulinaemia also contributes to hypertension, elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.8,9,10 Untreated, the diagnosis of type 2 diabetes usually occurs within a few years.11 However, hyperinsulinaemia may be present 15 years before elevated glucose and other symptoms of diabetes or metabolic syndrome become clinically meaningful, providing a window for prevention and treatment.12

Each individual symptom of metabolic syndrome increases the risk of diabetes and coronary artery disease. Combined, the risk amplifies. Even erectile dysfunction,13 Alzheimer's disease,14 polycystic ovary syndrome,15 and some types of cancer (eg, of the breast)16 have been linked to hyperinsulinaemia or metabolic syndrome. In fact, elevated insulin and glucose stimulate inflammation, creating a potential link to every chronic degenerative disease process.

Worldwide problem
The prevalence of metabolic syndrome in the United States has been estimated at somewhere between 39 million17,18 and 10019 million adult cases, the majority of which remain undiagnosed.17,18,19 In England, metabolic syndrome is strongly stratified along income, with more than one fifth of poorer men and women having the condition — two to three times the prevalence among wealthier men and women.20

Worldwide, the prognosis is grim, with diabetes being the eventual outcome. According to a recent report in the New England Journal of Medicine, diabetes cases will probably soar to unprecedented levels by 2030. Although the researchers projected a 72 per cent increase in diabetes in the United States and a 32 per cent increase in Europe, diabetes will jump by 164 per cent in the Middle East, 150 per cent in India, 104 per cent in China and 148 per cent in South America. Currently, an estimated 246 million people worldwide have diabetes. That number is expected to climb to 420 million in less than 20 years.21

Natural ingredients
Individual nutritional ingredients, in supplements or functional foods, can help improve insulin function, glucose control, and other signs and symptoms of metabolic syndrome. They function by providing the natural building blocks for a variety of biochemical pathways. Based on published research, the top-tier ingredients include alpha-lipoic acid and R-lipoic acid, chromium, biotin, Pycnogenol, and silymarin. (See the sidebar below for other important ingredients.)

Some ingredients, such as chromium and biotin, have been tested in combination. However, no individual ingredients have been found helpful in treating all aspects of metabolic syndrome in people. As a general rule, ingredients that reduce the risk of diabetes will likely reduce symptoms of metabolic syndrome. The ideal approach to product formulation would be to address most or all of the symptoms of metabolic syndrome.

Alpha-lipoic acid and R-lipoic acid have long been used as prescription drugs in Germany to treat diabetic nerve disease. Alpha-lipoic (thioctic) acid improves insulin function and is also a potent antioxidant. The latter is important because many of the complications of diabetes involve free radical damage and alterations in gene expression and cell signaling.22 Alpha-lipoic acid also plays co-enzymatic roles in the Krebs cycle, where glucose and fats are burned for energy.

Several large clinical trials have confirmed the benefits of alpha-lipoic acid in improving insulin function and reducing insulin resistance, even when blood glucose levels remain steady.23 That's important because of the health hazards of elevated insulin.

Stabilising insulin and blood glucose levels tends to reduce hunger jags and overeating, a common problem in metabolic syndrome. However, according to an animal study, lipoic acid may have appetite-reducing benefits via a different mechanism. Researchers reported in Nature Medicine that lipoic acid suppressed AMP-activated protein kinase, a hunger-regulating enzyme in the hypothalamus gland. Alpha-lipoic acid supplements reduced appetite, weight and blood glucose levels in laboratory rats. 24

Alpha-lipoic acid contains equal amounts of both S and R isomers, although research suggests that the R form is the more natural and biologically active part of the molecule.25 R-lipoic acid may be an alternative. However, most of the clinical research has used alpha-lipoic acid, and R-lipoic acid is more difficult to produce and more expensive than the alpha form.

Chromium is an essential dietary mineral that potentiates insulin function, leading to the cellular uptake and metabolism of blood glucose. Chromium deficiency results in symptoms similar to those of metabolic syndrome and diabetes, including elevations in blood lipids and decreases in glucose tolerance.26 Chromium supplements can improve insulin function and reduce blood-sugar levels over several months.27

Chromium picolinate, polynicotinate (niacin-bound), and glycinate are the most common forms found in supplements. However, most clinical studies over the past 10 years have used the picolinate and polynicotinate forms. Supplementation studies have found that 1,000mcg daily seems to be the ideal dose for people with diabetes. 28 Smaller amounts may be useful in less severe glucose intolerance.

Recent studies by Harry Preuss, MD, of Georgetown University, have found that chromium polynicotinate (600mcg/day for three months) lowered blood-sugar levels.29 Another study by Preuss found that chromium polynicotinate promoted fat loss but preserved muscle in overweight women.30 Meanwhile, other researchers found that chromium picolinate reduced weight gain from the diabetes drug glipizide.31

Biotin is a B-complex vitamin essential for the manufacture of insulin, and it also has insulinlike activity. Biotin regulates genes involved in the metabolism of glucose, amino acids and fatty acids.32 Clinical trials of biotin have led to reductions in triglyceride levels, but not in other signs of diabetes or metabolic syndrome.33 However, combining chromium picolinate (600mcg daily) with biotin (2,000mcg daily) has yielded more promising results, with reductions in blood glucose and HbA1c (which reflects glucose levels over six weeks), as well as improvements in blood-lipid ratios over periods ranging from one to three months.34,35,36

Pycnogenol is extracted from the bark of French maritime pine trees. This natural antioxidant complex inhibits the activity of alpha-glucosidase, one of the key enzymes that breaks down sugars and carbohydrates during digestion. The mechanism is similar to the diabetes drug acarbose, but a study found Pycnogenol 190 times more potent than acarbose in inhibiting alpha-glucosidase. As a result, some carbs pass through the gut without being broken down into glucose or stored as fat.37

Pycnogenol can also lead to significant reductions in fasting blood sugar and post-meal increases in blood sugar. In one study, people with diabetes took 50mg of Pycnogenol daily for three weeks and benefited from an average 10 per cent decrease in fasting blood-sugar levels. The benefits increased with larger amounts of Pycnogenol, topping out at 200mg daily with a 13 per cent reduction in fasting blood sugar.38

Silymarin, the antioxidant extract of the herb milk thistle (Silybum marianum) enhances liver function — significant because this organ works in tandem with the pancreas to regulate blood-glucose levels. In a 12-month study, 600mg daily of silymarin reduced blood-sugar levels in seriously ill diabetic patients by 13 per cent to 15 per cent. The patients also benefited from less sugar in the urine, lower HbA1c levels and smaller insulin requirements.39

A more recent study involved 51 diabetic patients, who took either 200mg of silymarin three times daily or placebos for four months. Silymarin supplementation led to striking improvements in almost every indicator of glucose tolerance and cardiovascular disease. Fasting blood sugar decreased from an average of 156mg/dl to 133mg/dl, a decline of almost 15 per cent. Glycated hemoglobin (HbA1c), a marker of average glucose levels, went from 7.8 to 6.8 per cent, a drop of almost 13 per cent, over about six weeks. In addition, insulin levels declined by 25 per cent, and total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels decreased significantly.40

Fibre/starch blockers are intriguing because one of the traits of metabolic syndrome is hypersensitivity to carbohydrates, especially sugars.41 High-fibre, low-glycaemic foods have long been known to reduce blood-glucose, insulin and lipid levels.42,43 Fibre speeds bowel transit time, allowing for less absorption of starches and sugars, while low-glycaemic carbohydrates result in moderate increases in blood-glucose and insulin levels. Several proprietary fibre products (eg, PGX) are sold at the retail level and are not yet available as raw materials. Although starch blockers, such as Phase 2 starch neutralizer, work through a mechanism different from that of fibre, they do seem to have similar benefits.44

Jack Challem is author of Syndrome X (Wiley, 2000), and The Food-Mood Solution (2007). His next book, Stop Prediabetes Now , will be published in November 2007. Respond: [email protected]

"The prevalence of metabolic syndrome in the United States has been estimated at somewhere between 39 million and 100 million adult cases…."
"As a general rule, ingredients that reduce the risk of diabetes will likely reduce symptoms of metabolic syndrome …"

Ingredients for individual symptoms of metabolic syndrome

  • Elevated glucose: bitter melon, chromium/biotin combination, cinnamon, magnesium, N-acetylcysteine, Pycnogenol, silymarin.
  • Insulin resistance: alpha-lipoic acid, biotin, chromium, silymarin.
  • Hypertension: L-arginine, Maitake mushrooms, omega-3 fatty acids, Pycnogenol
  • Elevated triglyceride: biotin, omega-3 fatty acids.
  • Elevated cholesterol/LDL: cinnamon, Maitake mushrooms, niacin, phytosterols
  • Appetite and weight reduction: alpha-lipoic acid, fibre, starch blockers, vinegar60


Functional Ingredients

  • Alpha-lipoic acid. Improves insulin function and reduces insulin resistance, even when blood-glucose levels remain steady.
  • Biotin. Helps make insulin and has insulinlike activity. Reduces triglycerides. Combined with chromium, reduces blood glucose and improves blood-lipid ratios.
  • Chromium. Improves insulin function and reduces blood-sugar levels.
  • Fibre/Starch blockers. Reduce absorption of starches and sugars.
  • Pycnogenol. Helps break down sugars and carbs. Reduces blood-sugar levels.
  • Silymarin. Helps regulate blood glucose levels by enhancing liver function.
Other potentially helpful natural compounds: Limited research has found that these substances may be helpful in some of the symptoms of metabolic syndrome and diabetes.
  • Bitter melon. Extracts of this green gourd have been shown to reduce blood-glucose levels in cell, animal and human studies.46
  • Cinnamon. Two recent studies found that cinnamon reduced fasting blood glucose, post-prandial glucose increases and blood lipids. A third study found no benefits.47,48
  • Fenugreek. Soluble fibre in fenugreek seeds slows carbohydrate absorption and boosts insulin activity.49
  • Green tea. Primary catechin EGCG improves insulin sensitivity, improves glucose utilisation and metabolism, and acts as an antioxidant.50
  • L-arginine. The precursor to nitric oxide, L-arginine is a vasodilator and can lower blood pressure.45
  • Magnesium. This essential mineral can lower fasting blood sugar and raise the 'good,' high-density lipoprotein form of cholesterol.51
  • Maitake mushrooms. Some evidence indicates that glycoprotein extracts Grifola frondosa may benefit those with diabetes, hypertension, elevated blood lipids and overweight issues.52
  • N-acetylcysteine. This sulfur-containing supplement may help improve glucose tolerance.53
  • Omega-3 fatty acids. These healthy fats reduce insulin resistance and triglyceride levels; their anti-inflammatory effects may also reduce diabetic complications.54
  • Phytosterols. These plant extracts can lower total cholesterol and LDL cholesterol almost as impressively as medications.55
  • Vanadyl sulfate. Regarded as an insulin mimic, this mineral compound may improve insulin resistance.56



Mini directory

Fibersol-2 digestion-resistant maltodextrin is a highly soluble fibre that is stable, has low viscosity, is transparent in solution and adds virtually no flavor to the finished product.

VitaSugar food ingredient is a prebiotic fibre and low-caloric nutritive sweetener suitable for baked goods, confectionaries, milk products, sweets and sweets-related products. It is stable above 320 degrees F.

Corowise brand plant sterols are taking the mainstream beverage world by storm, from Minute Maid orange juice to Rice Dream rice milk, as well as incorporation into breads, bars, cheeses and more.

Fish oil-derived oils and powders are taste- and odour-free, and suitable for the range of foods, supplements and pet products.

FenuLife brand fenugreek is an odourless and tasteless fenugreek extract for dietary supplements, foods and cosmetics.

Integrity Nutraceuticals
Cinnulin PF is a patented, concentrated cinnamon (Cinnamomi cassia) extract. The 100 per cent water-soluble product undergoes a specialised extraction process that maintains the natural content of cinnamon's polyphenol polymers.

ChromeMate (generically called chromium nicotinate, chromium polynicotinate or niacin-bound chromium) is a patented oxygen-co-ordinated niacin-bound chromium complex that plays an important role in proper insulin function, maintenance of healthy blood sugar and cholesterol levels, normal energy production, and promotion of healthy body weight.

Maitake Products
SX-Fraction is available in a standardised extract form as a raw material lableled "PSX-Fraction" to qualified manufacturers. The ingredient has been awarded a US patent as a blycoprotein with antidiabetic, antihypertensive antiobesity and antihyperlipidemic effects Grifola frondosa.

Martek Biosciences
life'sDHA is algae-derived DHA suitable for supplements, foods, beverages and infant formula.

Natural Health Science
Pycnogenol French maritime pine bark extract is exclusively distributed in North America by NHS. German company Horphag Research is the original supplier.

Next Pharmaceuticals
Chromulin is a new patented form of chromium that is stable, water soluble, and with superior absorption. It is a natural combination of the essential mineral chromium III with the essential amino acid histidine.

Ocean Nutrition Canada
meg-3 brand omega-3 fish oil has a patented Powder-loc micro-encapsulation technology making it state of the art for food and beverage integration without off-flavours or odours.

Pharmachem Labs
Phase 2 starch neutralizer and its food-friendly counterpart, Starchlite, are extracts of white kidney beans and both are GRAS.



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