November 15, 2010
All of Americas bad food and lifestyle choices have culminated into conditions such as diabetes and high cholesterol; and now, a growing number of consumers are being diagnosed with a new monster: metabolic syndrome. Metabolic syndrome is a comprehensive condition that comprises five main physiological markers: an elevated waist circumference (men > 40 inches, women > 35 inches); elevated triglycerides (> 150 mg/dL); reduced high-density lipoprotein (HDL) (men < 40 mg/DL, women < 50 mg/dL); elevated blood pressure; and elevated fasting glucose, according to The American Heart Association (AHA) and the National Heart, Lung and Blood Institute. Metabolic syndrome or, as some call it, syndrome X is diagnosed when a patient shows three or more of the markers. According to the American Heart Association (AHA), an estimated 50 million Americans are affected by symptoms associated with metabolic syndrome, said Matt Phillips, president of Cyvex Nutrition. The AHA also states the dominant underlying risk factors for this syndrome appear to be abdominal obesity and insulin resistance. In addition, Medco Health Solutions reports suggest the average yearly pharmacy cost of treating adult patients older than age 20 with metabolic syndrome exceeds $4,000more than four times the average annual drug spend for all other patients.
This beastly syndrome addresses three major components of health: heart health, blood sugar and weight management. Sure, pharmaceutical companies have drugs that address cholesterol, blood pressure, blood sugar, obesity and more; but, consumers arent interested in the pharma giants approach to these health concerns.
Weve noticed consumers are increasingly interested in novel, naturally derived ingredients that are backed by scientific research and safety trials, Phillips said. Hes right. Consumers are looking for natural ways to combat weight, glucose and heart issues minus the side effects many pharmaceutical methods have. And, as Phillips pointed out, theyre looking for more economical ways to thwart metabolic syndromes hold on their health. However, these products need to be substantiated; otherwise consumers wont be interested, as Catherine Lecareux, marketing manager of Bioserae, highlighted. If the industry wants to match the needs of this growing population suffering from syndrome X-related troubles, they should pay attention to what consumers really want, she said. Consumers are indeed in need for strong proof that would make them trust the products and the industry. They are more demanding about the origin and the quality of the products they consume, and they now pay a great attention to what the industry offers them.
But lean lightly on the use of supplements, and functional foods and beverages. The natural products industry needs to be careful not to overlook the underlining issues that cause metabolic syndrome: overeating, stagnant lifestyles, poor diet, etc., as Frank Schonlau, Ph.D., director of scientific communications, Horphag Research and Natural Health Science, pointed out. For the industry, it will be extremely important to ensure that an ethical position is taken on this issue, he said. For a person affected by obesity and metabolic syndrome, it is tempting to take products that are suggested to compensate for an unhealthy lifestyle. This, in turn, allows individuals to continue bad habits, including overeating, poor choices of unhealthy foods and lack of exercise. For the industry, it may be equally difficult to resist from meeting the demand for compensatory products. We in the industry have a responsibility not to exaggerate our abilities to help these conditions. Education of people affected by obesity and metabolic syndrome is critical; unfortunately, it is easier said than done, especially for the natural products industry, to get involved and contribute.
Elizabeth Bertani, vice president of marketing, Sprunk-Jansen LLC, agreed with Schonlaueducation is essential, and motivating consumers to jumpstart their health with diet and exercise is just as important as supplementing. The natural products industry can significantly and positively impact this epidemic, and it starts with consumer education and motivationmotivating people to be proactive about their health by taking responsibility for their dietary and lifestyle choices, she said.
Starting with basic nutrition is a good first line of defense. The types and amounts of foods we eat can directly contribute to our health and the incidence of these conditions, said Jim Komorowski, vice president, technical services and scientific affairs, Nutrition 21.
A 2010 study suggested a low-intensity lifestyle education program along with walnuts and flaxseed may help manage metabolic syndrome.1 Other studies have also supported walnuts role in loosening the grip of metabolic syndromes many fingers: A study published in Diabetes Care found a diet rich in walnuts helped type 2 diabetes patients improve endothelium-dependent vasodilatation and may reduce their overall cardiac risk;2 and Harvard researchers found high-walnut-enriched diets significantly decreased total and low-density lipoprotein (LDL) cholesterol during short-term trials.3 Green leafy vegetables, such as spinach, have also shown promising results via a 14-percent reduction in type 2 diabetes risk.4
It appears consumers are finally recognizing the foods we eat play a key role in the optimal health and disease prevention, as evidenced by the medical journals that are filled with such references, said Steve Holtby, president and CEO, Soft Gel Technologies Inc. (SGTI).
Attacking the Heart
Heart health has many components; the three major concerns related to metabolic syndrome are cholesterol, triglycerides and blood pressure. A ton of research has been conducted on myriad nutraceuticals that address these concerns.
Coenzyme Q10 (CoQ10) has strong scientific evidence supporting its role in heart health. An increasing number of scientific reports indicate dramatic decreases in CoQ10 levels and increased oxidative stress are associated with the aging process and with many age-related diseases, including metabolic syndrome, Holtby said.
One 2010 study found treatment with CoQ10 reduced cardiovascular risk associated with the metabolic syndrome.5 The results showed CoQ10 significantly decreased oxidative and inflammatory stress markers, prevented the elevation in serum insulin levels, reduced blood pressure and improved blood vessel health. A study with CoQsol®, a soft gel CoQ10 supplement branded by SGTI, showed basal CoQ10 levels increased significantly more with CoQsol than with dry-powder CoQ10 capsules after 30 days of supplementation in a randomized, placebo-controlled unpublished study. Reviews have also suggested CoQ10 may help lower systolic and diastolic blood pressure in hypertension.6,7
Omega-3s, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), help strengthen the heart. A Canadian, single blind, four-period, crossover study found an olive oil-based diet with fish-oil fatty acid esters of plant sterols, which included 5.4 g/d of EPA and DHA, may reduce cardiovascular disease (CVD) risk.8 In diabetic women, a higher consumption of fish and long-chain omega-3 fatty acids was associated with a lower coronary heart disease incidence and total mortality.9
In one trial of overweight individuals with insulin resistance, 50 percent of participants showed a clinically significant change in insulin-related function after taking DHA,10 Holtby noted.
In addition, researchers in Poland are currently conducting a study on EPAX AS DHA-rich 1050 TG formula for its potential effect on metabolic syndrome and its associated conditions. A series of studies, overseen by BIOCLAIMS, will be conducted through 2013 to determine what role marine-derived DHA plays on health factors such as central (waist) obesity, elevated blood pressure and triglyceride levels as well as prevalence of insulin resistance. The programs first study is under the direction of professor Aldona Dembinska-Kiec of the University of Poland, Krakow. He has designed a double blind, placebo-controlled study involving 300 patients to analyze several metabolic syndrome health markers.
Initial studies examining DHAs effect on metabolic syndrome have yielded promising results. We are encouraged that further inquiry will provide additional support for an increasingly taxing health condition, and we look forward to the programs study results as they become available over the coming years said Bjorn Refsum, CEO of EPAX AS.
Citrus bergamot is another ingredient with solid results for boosting heart health. HP Ingredients has conducted several human trials on its citrus bergamot. In a 2009 study, citrus bergamot demonstrated statin-like principles, carrying the 3-hydroxy-3-methylglutaric acid (HMG) moiety.11 And, in a separate human clinical, bergamot juice raised HDL by an average of 56 percent, while bergamot polyphenolic extract raised HDL by an average of 43 percent.12
Another interesting ingredient with heart-potential is NeOpuntia®, a patented lipophilic fiber made from Opuntia ficus-indica cactus leaves, from BioSerae. After a set of studies confirming NeOpuntias lipophilic properties and its ability to interact with fats, Bio Serae Laboratories conducted a larger clinical study designed to assess NeOpuntias ability to manage five risk factors typically associated with metabolic syndrome, Lecareux noted. This latest study indeed revealed another facet of NeOpuntia and highlighted its positive role in balancing blood lipid levels, parameters which are linked to syndrome X diagnosis. The six-week, monocentric, randomized, placebo-controlled, double blind study was conducted on 68 females with a body mass index (BMI) between 25 and 40, and diagnosed with metabolic syndrome.13 Half of the females consumed 1.6 g of NeOpuntia per meal and the other half a placebo. NeOpuntia improved HDL levels, and, at the end of the study, almost 40 percent of women in the treatment group were no longer diagnosed with metabolic syndrome. In women 45 years or older, NeOpuntia increased HDL-cholesterol and decreased levels of harmful triglycerides.
Pterostilbene is a natural analog of resveratrol found in berries such as blueberries, cranberries, sparkleberries, lingonberries and grapes. Pterostilbene acts as a PPAR-alpha agonist, which is involved in fatty acid and lipid catabolism, said Jeremy Bartos, Ph.D., ingredients product manager, pTeroPure, Inc. When activated, PPPAR-alpha acts to decrease triglyceride synthesis and lower LDL and very LDL (vLDL) levels.14,15 This phenomenon occurs in both hypercholesterolemic animals as well as healthy animals, suggesting it could be utilized in both cases: to block the synthesis of triglycerides that maintains high cholesterol levels in animals who already have it, and to prevent high cholesterol from popping up in those that dont."
Bartos added: We are also going forward with a human clinical study in conjunction with the University of Mississippi on pterostilbenes cholesterol and blood pressure lowering effects. The study is a randomized, double blind, placebo-controlled intervention study in 80 patients. The study will consist of a control group and pterostilbene administered at servings of 100mg/d and 250mg/d. We plan to have data by the beginning of next year with completion by July/August 2011.
From the vine to the ground, a couple of herbsloquat and olive leaf extractwork together to help maintain healthy cholesterol levels in Sprunk-Jansens product CHOLESTEROL LEVEL. In a double blind, randomized clinical study, carried out among 41 subjects, CHOLESTEROL LEVEL reduced blood cholesterol levels within a three-month period compared to placebo.16
Too Sweet for Their Own Good
Americans love their sugar. And this love affair is evident in our nations diet, as it revolves around sugar and starches. Problem is the body cant handle this forbidden affair and, in return, its developing conditions such as insulin resistance and diabetes.
The amount of starch and sugar that we consume in the United States simply overloads the bodys ability to manage such intake, leading to insulin resistance, said Scott Steil, president of Nutra Bridge Corp.
Holtby said: Metabolic syndrome occurs when insulin resistance is combined with high levels of blood fats (cholesterol and triglyceride), too much body fat and high blood pressure. Both insulin resistance and metabolic syndrome increase the risk of heart disease and diabetes (and many other serious, life-threatening diseases) because they impact, directly or indirectly, virtually every disease process.
So what is insulin resistance? According to Baldur Hjaltason, business development and sales director for EPAX, insulin resistance occurs when the hormone insulin, which possesses a series of effects on glucose and lipid homeostasis, does not get the same degree of effect in the liver, muscles and fat tissue. It is still not completely evaluated why some overweight people develop insulin resistance. Some natural compounds like fatty acids, in particular marine omega-3 fatty acids, interact positively with genes responsible for increasing fat and glucose metabolism.
The good news is there is natural hope for consumers. There are several solid options that the natural product industry offers to help in better blood sugar control and improved insulin function, Steil said. The key categories that our industry addresses include appetite suppressants, sweet craving control, reduced rate of glycolosis, insulin sensitizers, starch blockers and sugar blockers.
InSea2Canadian-based innoVactivs latest venture in the blood glucose category via polyphenols from brown seaweedsfunctions as a starch blocker. It reduces the rate at which complex carbohydrates (starch and table sugar) are converted to glucose in the food we eat, Steil said. This translates into the key benefit of reducing both peak and overall blood glucose levels, which also reduces the amount of insulin in the blood.
One study at Laval University, Quebec, found polyphenols from brown seaweeds, i.e., InSea2, may alter the acute glycemic and insulin response to carbohydrate ingestion, specifically, compared with placebo, subjects experienced a 3.6-reduction in plasma glucose concentration, a 5.9-percent reduction in insulin and a 6.9-percent increase in the Cederholm index of insulin sensitivity.17 In an unpublished animal study, InSea2 significantly reduced blood glucose in both lean and obese Zucker rats when it was administered orally together with table sugar during a four-week period.
Although omega-3s got their claim to fame in the heart-health market, they also have a positive effect on blood glucose and help normalize insulin resistance. It has been shown EPA and DHA bind to receptors on genes which are responsible for producing proteins, increasing fat burning and normalizing insulin resistance, Hjaltason said. Eating more fish seems to curb the negative effects of a sedentary lifestyle leading to metabolic syndrome. Since only a small portion of the American population consumes fish that is high in EPA and DHA, supplementation might be more logical. Regarding consumption of functional food and beverage, the dosage is most likely too small to have any real effects.
And, in the same respect, pterostilbene helps lower LDL cholesterol, it also plays a role in glucose management. Pterostilbene has also been shown in animal studies to regulate glucose metabolism by lowering blood sugar levels while raising insulin levels ,18 Bartos said.
Another ingredient that has a two-pronged approach to metabolic syndromeblood pressure19 and blood sugar20is French Maritime pine bark. Pycnogenol® potently inhibits an enzyme in the colon required for digestion of starch, Schonlau said. In turn, with Pycnogenol, starchy food doesnt cause a rush of sugars into the blood stream and prolongs the feeling of satiety. A series of clinical studies, most of which were carried out in the United States, have demonstrated a significant decrease of blood sugar levels even in people taking anti-diabetic medication with metformin or glitazones.
Moving on to minerals, chromium has a healthy reputation in the blood sugar category. Chromax chromium picolinate and Diachrome (chromium picolinate plus biotin) are nutrients clinically shown to improve insulin sensitivity and promote health glucose and lipid metabolism, Komorowski said. Chromium picolinate is the only nutrient with an FDA-approved qualified health claim in this area. More specifically, these ingredients can help individuals with metabolic syndrome or diabetes by lowering elevated blood glucose levels, decreasing elevated LDL cholesterol and increasing low HDL levels.
Pre-clinical research presented at the scientific sessions of the American Diabetes Association in 2006 indicated chromium picolinate may increase insulin sensitivity and glucose disposal.21 Additionally, a Canadian study reported obese rats that were administered oral chromium picolinate for three months exhibited improved insulin sensitivity and glucose disappearance as compared to control rats.22
GlucoHelp is an extract from the leaves of Lagerstroemia speciosa L., which is commonly known as banaba or crepe myrtle, Holtby said of the SGTI branded offering. GlucoHelp is standardized to contain 18-percent corosolic acid. Holtby also noted banaba grows in the tropics and the leaves have a high amount of corosolic acid, which has been known to exhibit anti-diabetic properties. In a randomized clinical trial involving type 2 diabetics, Lagerstroemia speciosa (as GlucoFit, from SGTI/Optipure) decreased blood glucose levels.23
Another product derived from plant extractsnettle, salt bush, walnut leaf extract and olive leaf extractis GLUCOSE LEVEL from Sprunk-Jansen. In 16 subjects with the onset of type 2 diabetes, GLUCOSE LEVEL reduced blood sugar levels after four weeks of supplementation.24
Fenugreek is also a plant-based ingredient. Promilin and Promilin Pro from TSI Health Sciences Inc. are patented bioactive extracts of 4-hydroxyisoleucine from Fenugreek seeds, said Sandy Chien, Ph.D., director, product development, TSI Health Sciences. 4-hydroxyisoleucine helps support the increase of glucose-induced insulin release through a direct effect on the pancreas that release insulin. Both in vitro and human clinical studies have demonstrated the products can promote healthy glucose and insulin utilization.
Not as familiar as omega-3s and chromium, D-Chiro-Inositol , a member of the inositol group of compounds, offers glucose-lowering benefits. Inositols are also referred to as sugar alcohol. Cyvexs branded product Chirositol is a natural ingredient thats designed to address both preventive and counteractive measures, Phillips said. Chirositol is extracted from carob pods and contains D-chiro-inositol, an important secondary messenger for insulin. Originating from the Mediterranean region with usage dating back to Ancient Egypt, carob tree fruit was considered an important source of sugar before sugarcane and sugar beets became widely available. In a 2010 three-week study, Chirositol, alone and in combination with manganese sulfate, significantly reduced blood glucose levels in diabetic mellitus-induced rats.25
The good news for those with elevated blood glucose and insulin resistance is there is a sweet alternative to sugar that is not only tolerated in diabetics, but it helps lower glucose levelscinnamon. Integrity Nutritions cinnamon ingredient, Cinnulin PF, has been the subject of numerous studies. In one study, 15 women with polycystic ovary syndrome (PCOS) one of the most common endocrinopathies among women of reproductive age in which 50 to 70 percent are diagnosed with insulin resistance, were randomized to daily oral cinnamon (as Cinnulin PF) or placebo for eight weeks.26 Comparisons of post-treatment to baseline insulin sensitivity indices using fasting and two-hour oral glucose tolerance tests showed significant reductions in insulin resistance in the cinnamon group, but not in the placebo group. A French study in 24 subjects with impaired fasting glucose administered 250 mg of an aqueous extract of cinnamon (as Cinnulin PF) two times per day for 12 weeks.27 The extract acted as an antioxidant and improved insulin sensitivity. A separate study funded by Integrity Nutrition through a CRADA (creative research and development agreement) with USDA and third-party contract laboratory organization Ohio Research Group was conducted on 22 subjects with prediabetes and the metabolic syndrome who supplemented with 500 mgs BID of Cinnulin PF yielded statistically significant decreases in fasting blood glucose, body fat and systolic blood pressure.28
As discussed before, education is essential. Whether educating consumers on what a healthy diet looks like and easy ways to incorporate physical activity into their daily life, or the importance of proper insulin function, consumers need to be educated. I think education is the biggest parameter of impacting this epidemic, said Tim Romero, vice president, Integrity Nutrition. The problem is most of those who are affected by poor insulin function yielding poor blood sugar metabolism are not even aware of it. The projections are alarming to say the least. Industry can impact this by pounding home the message that proper insulin function is the key to remaining healthy. Formulating with ingredients that support healthy insulin function is crucial and one step in the process, but the message and underlying education will ultimately dictate consumers gaining acceptance in this category.
Battle of the Belly
Weight management is a huge category. The natural products industry has generous amounts of weight management approachesfrom thermogenics to appetite suppressantsbut there are a few ingredients and products that address weight management in the context of metabolic syndrome.
Omega-3s are stealing the spotlight again, as not only do they address heart health and blood glucose stabilization, they also play a role in weight management.
Several trials have also shown when people suffering from metabolic syndrome are given omega-3 products high in DHA, they lose weight, Hjaltason said. It seems DHA activates gene expression to make several proteins that increase the metabolic burning leading to loss of weight. This is very important for those suffering from diabetic type 2, who usually are overweight, but also improves heart health by lowering the elevated triglyceride levels as well as improving the ratio between low and high density cholesterol in the blood.
Sprunk-Jansen also developed a product for weight maintenanceWEIGHLEVEL, a combination of Ladys Mantle leaves extract, olive leaves extract, cumin seed extract and wild mint leaves extract, which helps to control weight via appetite suppression, stimulating metabolism and easing digestion. A clinical study was carried out with 34 volunteers administered either WEIGHLEVEL or a placebo tablets three times daily.29 Weight reduction was observed each month in the test group, with an average of 1.65 lb per week. The average weight was reduced from baseline of 205 +/- 17.4 lb to 185 +/- 21.6 lb at three months. Similarly, progressive and significant weight loss was seen in the BMI, which was reduced after three months from 31+/-1.97 to 27.9 +/- 3.09. No significant effects were seen in the placebo group.
Metabolic syndromes grip on consumers is strong; and unfortunately, this market is bound to grow as diabetes, obesity and heart ailments are continually on the rise. The statistics are staggering, Romero noted. A recent stat suggested one in three Americans will be diabetic by 2050. That's a potential two- to three-fold increase in the next 40 years. According to the Center for Disease Control and Prevention (CDC), one in 10 adults has diabetes and one-quarter of them do not even know it. This alone impacts heart health and weight management statistics. The market is poised to grow substantially based on these staggering statistics, but it will require education to target these consumers. Consumers are still unaware of the causes and lack an understanding of the complexity of the metabolic syndrome.
As a result, the natural products industry has a responsibility to not only educate consumers, but to continue to research current and new ingredients in order to provide substantiated products that can help fight off and tame the metabolic syndrome beast.
References are on the next page...
References for "A Natural Approahc to Metabolic Syndrome"
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2. Yingying Ma, et al. Effects of Walnut Consumption on Endothelial Function in Type 2 Diabetic Subjects A randomized controlled crossover trial Diabetes Care. 2010;33(2):227-32
3. Deirdre K Banel and Frank B Hu Effects of walnut consumption on blood lipids and other cardiovascular risk factors: a meta-analysis and systematic review Am J Clin Nutr. 2009;90(1):56-63
4. Patrice Carter et al. Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis BMJ 2010;341:c4229
5. Kunitomo M, et al. Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome J Pharmacol Sci, 2008; 107(2): 128-37
6. Rosenfeldt F et al. "Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure." Biofactors. 2003;18(1-4):91-100
7. Houston MC. "The role of vascular biology, nutrition and nutraceuticals in the prevention and treatment of hypertension." JAMA. S1:5-71, 2002
8. Isabelle Demonty et al. Fish-oil esters of plant sterols improve the lipid profile of dyslipidemic subjects more than do fish-oil or sunflower oil esters of plant sterols1,2,3 Am J Clin Nutr. 2006;84(6):1534-42
9. Hu, FB et al. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women Circulation. 2003;107(14):1852-7
10. Mundell, EJ et al. Fish oil compound may help ward off diabetes Data presented by Pennington Biomedical Research Institute at the Experimental Biology 2002 conference .
11. Di Donna et al. Statin-like principles of bergamot fruit (Citrus bergamia) isolation of 3-hydroxymethylglutaryl flavonoid glycosides J Nat Prod. 2009 Jul;72(7):1352-4
12. Natalizia Miceli et al. Hypolipidemic Effects of Citrus bergamia Risso et Poiteau Juice in Rats Fed a Hypercholesterolemic Diet J. Agric. Food Chem. 2007, 55, 1067110677 10671
13. Linarès E, Thimonier C, Degre M The effect of NeOpuntia on blood lipid parameters--risk factors for the metabolic syndrome (syndrome X) Adv Ther. 2007 Sep-Oct;24(5):1115-25
14. Rimando AM et al. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters J. Agric. Food Chem. 53, 3403 (2005)
15. Mizuno CS et al. Design, synthesis, biological evaluation and docking studies of pterostilbene analogs inside PPARalpha. Bioorg Med Chem. 16, 3800 (2008)
16. Omar S et al., 2009. Hypolipidemic Activity of Extracts from Eriobotrya japonica and Olea europaea, Traditionally Used in the Greco-Arab Medicine in Maintaining Healthy Fat Levels in the Blood. The Open Complementary Medicine Journal, 1: 84-91
17. Benoit Lamarche1, Marie-Ève Paradis1 and Patrick Couture Benoit Lamarche1, Marie-Ève Paradis1 and Patrick Couture FASEB. April 2010
18. Pari L, Satheesh MA. Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin and nicotinamide induced diabetic rats. Life Sci. 79, 641 (2006)
19. Ximing Liu, MD et al. French Maritime Pine Bark Extract Pycnogenol Dose-Dependently Lowers Glucose in Type 2 Diabetic Patients Diabetes Care 2004;27(3):839
20. Liu, X., Wei, J., Tan, F., Zhou,S., Wurthwein, G. and Rohdewald, P. (2004) Antidiabetic effect of Pycnogenol® French maritime pine bark extract in patients with diabetes type II.Life Sci. 75 : 2505-2513.
22. Cefalu WT et al. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats J Nutr. 2002;132(6):1107-14
23. Judy WV et al. Antidiabetic activity of a standardized extract (Glucosol) from Lagerstroemia speciosa leaves in Type II diabetics. A dose-dependence study J Ethnopharmacol. 2003 Jul;87(1):115-7
24. Omar S et al., 2008. Maintaining a physiological blood glucose level with 'Glucolevel', a combination of four anti-diabetes plants used in the traditional Arab herbal medicine. Evidence-Based Complementary and Alternative Medicine: eCAM 5(4): 421428.
25. Synergistic Effects of D-Chiro-Inositol and Manganese in Diabetic-Induced Rats; Current Bioactive Compounds; June 2010. http://www.cyvex.com/synergistic-effects-of-d-chiro-inositol-and-manganese-in-diabetic-induced-rats
26. Wang JG et al. The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study Fertil Steril. 2007 Jul;88(1):240-3
27. Isabelle Hininger, Tim N. Ziegenfuss, Richard A. Anderson Cinnamon Improves The Antioxidant Variables Of People With Impaired Fasting Glucose J Am CollegNutr.2009;28(1):16-21
28. Tim N. Ziegenfuss Effects of a Water-Soluble Cinnamon Extract on Body Composition and Features of the Metabolic Syndrome in Pre-Diabetic Men and Women Journal of the International Society of Sports Nutrition. 3(2): 45-53, 2006
29. Omar Said et al, 2010. A Double-Blinded Randomized Clinical Study with 'Weighlevel', a Combination of Four Medicinal Plants Used in Traditional Greco-Arab and Islamic Medicine. The Open Complementary Medicine Journal 2010, 2, 1-6.
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