Cardiometabolic syndrome (CMS) is the quintessential disorder of the late 20th century and the 21st century. It is comprised of metabolic dysfunctions primarily characterized by insulin resistance, impaired glucose tolerance, dyslipidemia (e.g. high cholesterol and triglycerides), hypertension, inflammation and central adiposity (a major contributor to increased cardiometabolic risk.)1,2 In fact, the World Health Organization and the American Society of Endocrinology has recognized CMS as a disease entity, and people with CMS are two times more likely to die from coronary heart disease and three times more likely to have a heart attack or stroke than those who do not have the syndrome. As it stands, about 25 percent of the world’s adults are suffering from this syndrome.3

While bringing CMS risk factors under control is challenging, there are cardiometabolic programs and therapeutic strategies existing that combine diet and exercise prescriptions and focus on behavioral change to maximize success in reducing cardiometabolic risk factors. The Mayo Clinic has outlined specific recommendations for calorie intake, nutrition, and ongoing cognitive and psychological assessments of habits and unhealthy behaviors.4 In addition, supplementation with a specific trivalent chromium/herbal complex (Crominex 3+ by Natreon) can also help reduce cardiometabolic risk factors. Before getting into a discussion about this specific trivalent chromium complex, let’s first briefly review chromium’s role in the body.

Chromium

Chromium is a mineral that humans require in trace amounts. It is found primarily in two forms: 1) trivalent (chromium 3+), which is biologically active and found in food, and 2) hexavalent (chromium 6+), a toxic form that results from industrial pollution. Chromium is known to enhance the action of insulin, a hormone critical to the metabolism and storage of carbohydrate, fat and protein in the body. In 1957, a compound in brewers’ yeast was found to prevent an age-related decline in the ability of rats to maintain normal levels of sugar (glucose) in their blood. Chromium was identified as the active ingredient in this so-called “glucose tolerance factor” in 1959.5

Biologically active trivalent chromium participates in glucose metabolism by enhancing the effects of insulin. Insulin binds to insulin receptors on the surface of cells, which activates the receptors and stimulates glucose uptake by cells. Through its interaction with insulin receptors, insulin provides cells with glucose for energy and prevents blood glucose levels from becoming elevated. In addition to its effects on carbohydrate (glucose) metabolism, insulin also influences the metabolism of fat and protein. A decreased response to insulin or decreased insulin sensitivity may result in impaired glucose tolerance or type 2 diabetes, also known as non-insulin dependent diabetes mellitus (NIDDM). Type 2 diabetes is characterized by elevated blood glucose levels and insulin resistance.6

Trivalent Chromium/Herbal Complex

Crominex 3+ is a trivalent chromium/herbal complex. The associated herbs include a standardized extract of Indian gooseberry and purified shilajit (mineral pitch). Human clinical research suggests that this chromium/herbal complex helps support healthy glucose levels, healthy endothelial function and healthy cholesterol levels.

Chromium/Herbal Complex In Type 2 Diabetes

To evaluate effectiveness on cardiometabolic parameters, a prospective, randomized, double blind trial7 was undertaken with chromium/herbal complex providing chromium 200 mcg (group 1), chromium 400 mcg (group 2) and placebo (group 3) in 60 patients with type 2 diabetes mellitus (T2DM). Subjects were reviewed for follow up at four, eight and 12 weeks of therapy. At each visit, they were evaluated for efficacy and safety. Results demonstrated several statistically significant effects. Treatment with chromium/herbal complex showed: 1) significant reduction in reflection index (suggesting improvement in endothelial function) with 200 mcg (p<0.001 compared to baseline and placebo) and 400 mcg (p<0.001 compared to baseline and placebo, and p<0.001 compared to 200 mcg); 2) significant increase in nitric oxide (which promotes circulation) with 200 and 400 mcg (p<0.001); 3) significant increases in glutathione (a critical antioxidant) with 200 and 400 mcg (p<0.001); 4) significant reductions in MDA (a marker for oxidative stress) with 200 and 400 mcg (p<0.001); 5) significant reductions in hsCRP (an inflammatory marker) with 200 and 400 mcg (p<0.001); and 6) significant reduction in glycosylated hemoglobin A1C (a measure of long-term glucose control) with 200 mcg (p<0.05) and 400 mcg (p<0.001). In addition, there were significant percentage changes in lipid profile after 12 weeks (see table). All these parameters were significant compared to baseline as well as placebo.

Furthermore, there were no significant changes in safety parameters, including vital, hematological, renal and hepatic functions with all treatments. In conclusion, treatment with chromium/herbal complex 200 mcg and 400 mcg produced significant improvement in mean reflection index, oxidative stress and lipid parameters. Treatment with chromium/herbal complex also significantly reduced glycosylated hemoglobin A1c levels compared to baseline and placebo. All the treatments were well tolerated, and no patient discontinued the study because of side effects.

Chromium/Herbal Complex In Metabolic Syndrome

Another prospective, randomized, double blind trial8 was undertaken to evaluate the effect of chromium/herbal complex providing chromium 200 mcg (group 1), chromium 400 mcg (group 2) and placebo (group 3), but this time in 61 patients with metabolic syndrome. Subjects were reviewed for follow up at four, eight and 12 weeks of therapy. At each visit they were evaluated for efficacy and safety. As with the prior study, results demonstrated several statistically significant effects. Treatment with chromium/herbal complex showed: 1) significant reduction in reflection index with 400 mcg (p<0.001); 2) significant increase in nitric oxide (which promotes circulation) with 400 mcg (p<0.001); 3) significant increase in glutathione with 400 mcg (p<0.001); 4) significant reduction in MDA (a marker for oxidative stress) with 400 mcg (p<0.001); and 5) significant reduction in hsCRP (an inflammatory marker) with 400 mcg (p<0.001). All these parameters were significant compared to baseline as well as placebo. In addition, there were significant percentage changes with chromium/herbal complex, compared to the placebo group: in LDL-cholesterol at both 400 mcg (p<0.001) as well as 200 mcg doses (p<0.01), and triglycerides (p<0.05), as well as an increase in HDL-cholesterol (the “good cholesterol”) at 400 mcg dose (p<0.01).

Chromium/Herbal Complex In Comparison to Other Forms of Chromium

A randomized, placebo-controlled, double-blind clinical study9 was conducted to evaluate the effect of chromium/herbal complex and its individual components in comparison to chromium picolinate, chromium polynicotinate and chromium dinicocysteinate on endothelial function, glycosylated hemoglobin and lipid profile in type 2 diabetics. The study was done in two parts. Part I was comprised of the type 2 diabetes study with chromium/herbal complex discussed previously. With part II, when the part I results were highly significant, especially with the 400 mcg dose, more patients were included (n=96) to evaluate the individual components of chromium/herbal complex and other branded chromium salts available in the market, at 400 mcg dose level. Results were that chromium/herbal complex significantly improved endothelial function and increased the levels of the nitric oxide and glutathione, and significantly decreased the levels of malondialdehyde and highly sensitive C-reactive protein at both 200 mcg and 400 mcg per day dose levels, with the results being much more significant at the 400 mcg dose level. Similarly, the effect on lipid profile was highly significant with improvement of lipid levels from 18 to 28 percent and a decrease of half a point in the glycosylated hemoglobin A1c level with the 400-mcg dose. The results from the chromium/herbal complex group were much more significant than the sum of the results from the individual component arms, indicating that chromium/herbal complex has significant synergistic activity. With respect to efficacy, chromium/herbal complex was the best, followed by the combination of Indian gooseberry and shilajit extracts (the two other components in chromium/herbal complex), chromium picolinate, chromium polynicotinate, chromium dinicocysteinate and the placebo, in that order. In conclusion, chromium/herbal complex improved endothelial function, nitric oxide, glutathione and hsCRP levels, lipid profile and glycosylated hemoglobin in type 2 diabetics and it appears to have a significant synergistic activity. In addition, chromium/herbal complex proved to be the most efficacious in the parameters tested among all the chromium products studied. Natreon was granted a U.S. Patent 10,183,047 in 2019 for this synergistic activity improving endothelial function and cardiovascular health.

Chromium/Herbal Complex In Combination With Oral Antidiabetic Drugs

Chromium/herbal complex was tested with conventional oral hypoglycemic drugs [oral antidiabetic drugs (OAD)] and placebo for its beneficial effects in T2DM patients. The OAD included glipizide, metformin and pioglitazone. A randomized clinical study10 with three OADs, with or without chromium/herbal complex, was carried out in 135 T2DM patients to evaluate the efficacy of the chromium/herbal complex supplement. The patients were randomized into six treatment groups. After 60 days of treatment, fasting blood glucose and post-prandial blood glucose (FBG and PPBG, respectively), glycosylated hemoglobin, hsCRP, oxidized low density lipoprotein (LDL), and urinary microalbumin levels (used to detect early signs of kidney damage) and other diabetic symptoms were evaluated. Results showed better control of FBG and PPBG levels were observed in patients receiving chromium/herbal complex (-12.4 to -16.6 percent) compared to placebo groups (-3.4 to -9.4 percent).

There was a 5.5–7.4 percent decrease in HsCRP and LDL levels in patients receiving chromium/herbal complex, which is better than placebo-treated groups. Significant decrease in urinary microalbumin level was observed in patients receiving chromium/herbal complex (-20.0 to -22.5 percent) compared to placebo groups (-7.8 to -11.6 percent). Significant decreases in diabetic symptoms were observed in patients receiving chromium/herbal complex (-47.4 to -59.4 percent) compared to that observed in placebo groups (-18.0 to 34.0 percent). T2DM patients who took chromium/herbal complex as an adjunct therapy experienced a better decrease in glycosylated hemoglobin (ranging from -5.2 to -6.7 percent; mean -6.1 percent) levels compared to that of only OAD treated groups (ranging from -2.1 to -6.2 percent; mean -4.1 percent). In conclusion, the findings indicate that chromium/herbal complex with OAD improves overall diabetic complications within two months and may be useful in long-term therapy.

Chromium/Herbal Complex In Combination With Fish Oil

The purpose of this 12-week randomized, double-blind, parallel group study11 was to evaluate the effectiveness of fish oil alone, and in combination with chromium/herbal complex, on cardiovascular parameters—endothelial dysfunction, lipid profile, systemic inflammation and glycosylated hemoglobin, in 59 T2DM subjects, already on a stable dose of metformin. Subjects were divided into three groups: Group A-fish oil 2,000 mg, Group B-fish oil 2,000 mg + chromium/herbal complex providing 200 mcg of chromium, and Group C-fish oil 2,000 mg + chromium/herbal complex providing 400 mcg of chromium daily for 12 weeks. The 2,000 mg of fish oil contained 600 mg of EPA (eicosapentaenoic acid) and 400 mg of DHA (docosahexaenoic acid), the omega-3 fatty acids. Endothelial function was measured by estimating reflection index, biomarkers of oxidative stress (NO, MDA, glutathione) and inflammatory biomarkers (hsCRP, ICAM-1, VCAM-1, endothelin-1) were evaluated at baseline, and four and 12 weeks. Lipid profile, platelet aggregation and HbA1c testing was done at baseline and 12 weeks. Results were that fish oil by itself showed significant, but only modest, improvement in cardiovascular parameters, including triglyceride levels. However, when chromium/herbal complex was added to fish oil, especially at the 400 mcg chromium dose, there were highly significant improvements in all the parameters tested, including the lipid profile. It is noteworthy that the triglycerides were decreased significantly by addition of 400 mcg chromium although the dose of fish oil was only 2 g/day and the baseline triglyceride levels were only about 200 mg/dL. Fish oil alone did not significantly decrease the glycosylated hemoglobin, while the addition of 400 mcg chromium did. Likewise, LDL cholesterol was also decreased significantly, which is especially meaningful since some studies have shown in increase in LDL with fish oil supplementation. A decrease in hsCRP was also demonstrated. In conclusion, the addition of chromium/herbal complex, especially at the dose providing 400 mcg mg chromium significantly improved the efficacy of fish oil in addressing cardiovascular risk factors when compared to fish oil given alone.

A similar study with fish oil and the chromium/herbal complex in a metabolic syndrome population is currently awaiting publication.

Conclusion

Approximately 25 percent of adults suffer from cardiometabolic syndrome, which includes insulin resistance, impaired glucose tolerance, dyslipidemia (e.g. high cholesterol and triglycerides), and inflammation, among other factors. In addition to diet, exercise and behavior modification techniques, supplementation with a trivalent chromium/herbal complex can also help reduce cardiometabolic risk factors. This has been demonstrated in several studies where this chromium/herbal complex successfully reduced blood glucose levels, cholesterol levels, triglyceride levels and inflammatory markers when used alone or in combination with oral hypoglycemic medications, or fish oils. Additionally, Crominex 3+ has been shown to be more effective at reducing cardiometabolic parameters in a direct comparison between other forms of chromium, including chromium picolinate, chromium polynicotinate and chromium dinicocysteinate. VR

References:

1 Esser N, Paquot N, Scheen AJ. Inflammatory markers and cardiometabolic diseases. Acta Clin Belg. 2015 Jun;70(3):193-9.

2 Saljoughian M. Cardiometabolic Syndrome: A Global Health Issue. US Pharm. 2016;41(2):HS19-HS21.

3 Srivastava AK. Challenges in the treatment of cardiometabolic syndrome, Indian J Pharmacol. 2012;44(2):155-156.

4 Mayo Clinic. Cardiometabolic program. Overview. www.mayoclinic.org/departments-centers/cardiovascular-diseases/overview/specialty-groups/cardiometabolic-program/overview. Accessed January 18, 2017.

5 Dietary Supplement Fact Sheet: Chromium. National Institutes of Health, Office of Dietary Supplements. Updated: July 9, 2019. Retrieved February 22, 2020 from https://ods.od.nih.gov/factsheets/Chromium-HealthProfessional/.

6 Food and Nutrition Board, Institute of Medicine. Chromium. Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, D.C.: National Academy Press; 2001:197-223.

7 Rani PU, Sravanti IV, Fatima N, Muralidhar N, Salomi R. Study of Crominex 200mcg, 400 mcg and Placebo in modifying cardiovascular risk with special reference to Endothelial dysfunction in patients with Type2 Diabetes Mellitus. Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India. December Unpublished; 2013: 24 pgs.

8 Rani PU, Sravanti IV, Fatima N, Muralidhar N, Salomi R. Study of Crominex 200mcg, 400mcg and Placebo in subjects with Metabolic Syndrome. Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India. December Unpublished; February 2014: 24 pgs.

9 Rani PU, Sravanthi IV, Kumar CU, Kishore KK, Devi CG. Randomized, placebo-controlled, double-blind clinical study to evaluate the effect of a proprietary chromium complex and its individual components in comparison to chromium picolinate, chromium polynicotinate and chromium dinicocysteinate on endothelial function and lipid profile in type 2 diabetics. Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India. December Unpublished; February 2016: 58 pgs

10 Tuhin BK, Polley G, Pandit S, Pratip DK, Somoresh M, Biswajit A, Banerjee D, Bhattacharyya S, Debasish P, Ghosal S. Effects of adjunct therapy of a proprietary herbo-chromium supplement in type 2 diabetes: A randomized clinical trial. Int J Diab Dev Ctries. 2010;30(3):153-61.

11 Pingali U, Nutalapati C, Illendulla VS. Evaluation of the effect of fish oil alone and in combination with a proprietary chromium complex on endothelial dysfunction, systemic inflammation and lipid profile in type 2 diabetes mellitus – A randomized, double-blind, placebo-controlled clinical study. Department of Clinical Pharmacology & Therapeutics, Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad, Telangana, India. n.d. 22 pgs.

Gene Bruno, MS, MHS, the dean of academics for Huntington University of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at gbruno@hchs.edu.