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Chromium Picolinate: Nutritional Support for Type 2 Diabetes
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Can nutritional supplements (such as chromium picolinate) really provide nutritional support to improve glycemic control in persons with type 2 diabetes?
by Seth Bronheim
What is Chromium?
Chromium is a trace mineral essential for the metabolism of carbohydrates, lipids, and proteins. Chromium acts as a cofactor for insulin function that increases the binding of insulin, the number of insulin receptors, and insulin receptor phosphorylation. Chromium allows insulin to work properly so there can be optimal glucose transport into muscle, liver, and adipose tissue (1). Chromium was first identified in 1959 as an element to enhance insulin action and restore normal glucose tolerance in rats (2). Currently, not only are adults in the United States consuming less than adequate intake of chromium which is 25 to 35 micrograms per day, but levels of serum chromium have been reported to decrease with aging (3).
Chromium and Diet
Examples of dietary sources of chromium are whole grains, cheese, liver, and meat. In addition, the refining of grains removes most of the absorbable chromium (1). Further evidence has shown that the chromium requirement is related to the degree of glucose intolerance (4). In addition, diets high in sugar have been shown to increase chromium losses. In persons with type 2 diabetes, chromium metabolism is altered by an inadequate intake of chromium, and increased chromium losses, which cause abnormal blood, tissue, and urine levels of chromium. Persons with diabetes usually show high urine levels of chromium, which may be caused by a high sugar diet as previously discussed, or that the chromium was not reabsorbed by the kidneys. The deficiency of chromium is one reason for the impaired glucose tolerance and insulin resistance shown in persons with diabetes (1).
Chromium Absorption
It is important to note that the bioavailability of chromium is low and dietary chromium absorption varies from 0.4 to 2 percent. Some researchers believe that in order for chromium to become biologically active and help with insulin function, it must be bound with another molecule (3). Chromium has the ability to bind with ligands such as picolinate, and form larger complexes (2). It has been shown that chromium picolinate has a higher absorption rate of 0.7 to 5.2 percent (3). In addition, several studies have shown chromium picolinate to have a higher absorption rate than other forms of chromium. Evidence has shown that chromium picolinate reached higher tissue concentrations in muscle, liver, and heart as compared to chromium chloride, chromium polynicotinate, or chromium histidinate (1).
What does the research have to say about chromium picolinate?
Anderson RA, Cheng N, Bryden NA; et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes. 1997;46:1786-1791.
Anderson et al (1997) was one of the earlier studies done on chromium picolinate and diabetes and was the first study to have a four month treatment period (5). Previous studies on chromium picolinate were at most two months (1). This study by Anderson et al had 180 Chinese subjects with type 2 diabetes, between the ages of 35 to 65 years. The subjects had a fasting glucose level between 130 and 279 mg/dL, a 2-hour glucose concentration between 170 and 300 mg/dL (after a 2-hour glucose challenge using 75 grams of glucose), and an HbA1c level of 8 to 12 percent. In this study, 60 subjects received a placebo treatment, 60 received 100 mcg twice per day of chromium picolinate, and 60 subjects received 500 mcg twice per day of chromium picolinate. It should be noted that subjects were instructed to continue taking their normal medications for diabetes such as oral hypoglycemics, traditional Chinese medicine, and insulin. The results of this study were that there were significant improvements in fasting glucose, postprandial glucose, fasting insulin, and postprandial insulin. Fasting glucose concentrations and 2-hour glucose concentration were significantly lower in the group receiving a total of 1000 mcg/day of chromium picolinate at two and four months. Both groups receiving chromium picolinate also had significantly lower fasting insulin concentrations after two months, and at four months both groups actually had identical values for fasting insulin concentration. After four months, insulin concentrations (after a 2 hour glucose challenge) were also significantly lower, and similar in both groups. HbA1c levels were also significantly lower after four months in both groups receiving chromium picolinate. The group receiving 1000 mcg/day had actually demonstrated a quicker drop in HbA1c, and also showed a significantly lower level of HbA1c after two months, which remained significant at four months. It should be noted that the placebo group had reductions in fasting and two-hour glucose concentrations, which is most likely due to subjects continuing to take diabetic medications. Body weight did not change significantly throughout this study, so the improvements seen in this study are not due to changes in body weight. This study shows that after a four month period, both a 200 mcg/day and 1000 mcg/day dose of chromium picolinate have very similar and beneficial effects on insulin and glucose variables (5). Reductions in glucose and insulin variables in this study were seen with a lower dose of 200 mcg/day, and a higher dose of 1000 mcg/day. However, this study showed that the higher dose of 1000 mcg/day had a significantly larger reduction in fasting glucose concentrations, as well as 2-hour glucose concentrations. This study also demonstrates that chromium picolinate is an effective complement to the conventional treatment of type 2 diabetes.
Ghosh D, Bhattacharya B, Mukherjee B; et al. Role of chromium supplementation in Indians with type 2 diabetes mellitus. J Nutr Biochem. 2002;13:690-697.
The aims of another study were to evaluate chromium status and to assess the effect of chromium picolinate supplementation on glycemic control in Indian subjects, with type 2 diabetes (6). The study was a double blind, placebo-controlled, crossover fashion, with each treatment arm lasting 12 weeks with a 4 week washout period in between. There were 50 subjects (mostly between the ages of 40 to 60 years) who had type 2 diabetes, and treated it with diet alone, or with diet and oral hypoglycemic agents. Moreover, the subjects continued to use oral hypoglycemic agents throughout the study without altering the dose (which was also done in the previous study by Anderson et al). All of the subjects had reasonably stable blood glucose levels for the three months prior to the study. The chromium picolinate dose in this study was 200 micrograms, twice daily. The results of this study showed that subjects with type 2 diabetes were found to have lower serum chromium levels than the healthy controls. However, it should be noted that the authors of this study stated that serum chromium levels do not reflect tissue levels as tissue levels of chromium are ten times higher than serum chromium levels. This study did however show that serum chromium did increase slightly after the 12 week supplementation period. The chromium-treated group also had a significant reduction in fasting serum insulin (256 to 206 pmol/L), fasting plasma glucose (124 to 115 mg/ dl), and post-prandial glucose (220 to 183 mg/dl) (6). The decline in fasting serum insulin reiterates one of the underlying mechanisms of chromium picolinate, which is improving insulin action. This study shows that chromium picolinate alone, can be beneficial for glycemic control, and is also an effective complement to the conventional treatment of type 2 diabetes.
Martin J, Wang ZQ, Zhang XH; et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care. 2006;29:1826-1832.
A study done by Martin et al, assessed the effect of supplemental chromium picolinate, in combination with the oral hypoglycemic agent, glipizide (Glucotrol) (7). Glipizide is a hypoglycemic medication that works by stimulating insulin release from beta cells in the pancreas. Instead of subjects being on various conventional treatments of type 2 diabetes, all subjects were on the exact same oral hypoglemic agent, and the exact same dosage. This research methods design helps standardize the treatment of the study. In this study, there were 37 subjects with type 2 diabetes, and they were required to have a fasting blood glucose of greater than 125 mg/dL, but less than 170 mg/dL. Subjects on diabetic medications were excluded. This study was double blinded, randomized, and placebo controlled. It started with a one month washout period (baseline). After the washout period, 8 subjects withdrew from the study due to various reasons. The washout period was followed by a three month period of treatment with just 5 mg/day of glipizide only (period 1), followed by a six month period where one group (17 subjects) received 5 mg/day of glipizide and 1000 mcg/day of chromium picolinate (500 mcg capsule twice per day), and the other group (12 subjects) received glipizide (5 mg/day) with two placebo capsules. During the treatment periods, subjects were instructed on a weight maintenance diet and home glucose monitoring. The results of the first 3 month period (period 1) of this study showed a significant decrease in fasting glucose levels in all subjects as well as a significant decrease in HbA1c. This is an expected result due to the start of a hypoglycemic agent. At the end of period 2 (after a six month treatment period) as compared with baseline, subjects in the glipizide with chromium picolinate group had significantly lower fasting glucose levels compared to the glipizide with placebo capsules group. The group receiving both glipizide and chromium picolinate, also maintained a significant decrease in HbA1c, while the glipizide and placebo capsules group did not maintain the decrease in HbA1c. Another important result is that subjects in the group receiving both glipizide and chromium picolinate had significant improvements in insulin sensitivity, when compared to the group receiving glipizide and placebo capsules (7). The results of this study show that adding chromium picolinate supplementation in addition to glipizide significantly improves glycemic control and enhances insulin sensitivity compared with subjects just on glipizide treatment. This study shows the enhanced benefit of combining traditional medicine (glipizide) with complementary medicine (chromium picolinate), which has also been shown in previous studies discussed.
Kleefstra N, Houweling ST, Jansman, FG; et al. Chromium treatment has no effect in patients with poorly controlled, insulin treated type 2 diabetes in an obese western population. Diabetes Care. 2006;29:521-525.
The aim of a study done by Kleefstra et al was to determine the effect of chromium picolinate on persons with insulin-dependent type 2 diabetes. In addition to insulin, subjects in this study may have also been taking other diabetic medications. This was a six month double-blind study, that had 53 subjects with insulin requirements of greater than 50 units per day and a BMI greater than 25 (so all subjects were overweight according to BMI standards). In this study, the subjects were divided into the following three groups: one group of 19 subjects was given a placebo treatment, one group of 17 subjects received 250 mcg of chromium picolinate twice per day, and one group of 17 subjects received 500 mcg of chromium picolinate twice per day. Subjects were asked not to change their diet or insulin dosages throughout the six month treatment period. The results of this study showed no significant differences between groups. There was a very slight decrease in HbA1c across all three groups of approximately 0.4 percent. This study stated that based on their results, there is no convincing evidence that chromium therapy in an obese Western population will improve glycemic control. This statement is true based on the results, yet this study only used one marker of glycemic control, HbA1c (8). They did not test for changes in glucose or insulin variables such as fasting glucose concentration, fasting insulin concentration, 2-hour insulin, or glucose concentration after a 2 hour glucose challenge. Other studies use these glucose and insulin variables to test for changes in glycemic control. These variables are very important to test because glycemic control is not based on one marker (HbA1c). This study had very important objectives, because more research is needed on how chromium picolinate supplementation affects glycemic control in persons with insulin-dependent type 2 diabetes. This research is especially important for persons interested in combining complementary medicine with traditional medicine.
Cefalu W.T., Wang Z.Q., Zhang, X.H., Baldor L.C., Russell, J.C. 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;132:1107-1114.
One animal study wanted to evaluate whether chromium picolinate could aid in the insulin resistance syndrome, so the researchers assessed chromium picolinate in JCR:LA-corpulent rat subjects (9). This type of rat has genes that induce insulin resistance, obesity, a high triglyceride level, and develop advanced atherosclerotic disease and myocardial lesions. The subjects were randomly assigned to the treatment group (chromium picolinate), which consisted of six obese subjects and five lean subjects, or the control group, which had five obese subjects and five lean subjects. The chromium picolinate in this study was administered in water, and was diluted to achieve the target chromium intake per group. The chromium picolinate provided an intake of 80 micrograms/kg/day, which corresponds to approximately 18 micrograms of elemental chromium. The rat subjects in this study were fed a fixed formula diet. It should also be noted that there was elemental chromium provided in the diet in the amount of 0.4 mg/kg. This study had a 12 week treatment phase, and at the end of the phase, 120 minute glucose tolerance tests and 30 insulin tolerance tests, were performed to evaluate carbohydrate metabolism. The results of this study were that fasting insulin was lower in the chromium picolinate treated obese rats, than in the controls. What is interesting to note is that chromium picolinate had no effect on fasting insulin in lean rats. The results of the glucose tolerance tests showed that glucose and insulin were significantly less for obese rats treated with chromium picolinate compared to obese controls. The glucose levels in lean rats treated with chromium picolinate were similar to lean controls. This study is unique in that it tested the GLUT-4 transporter which, is responsible for transporting glucose to muscle and adipose cells. This study found that membrane-associated Glut-4 was greater in chromium picolinate treated rats than controls after insulin stimulation. The study stated that increased insulin signaling (from the chromium picolinate treatment in this study) would be expected to enhance the regulated movement of Glut-4, enhancing glucose disposal. The cellular mechanisms causing this effect are unknown, but are being researched. It is also unknown whether the JCR:LA-corpulent rat is chromium deficient. So one limitation of this study is the lack of blood or urine levels of chromium to determine chromium status, especially in the JCR:LA-corpulent rat. It should also be noted that the chromium dose in this study was much greater than the doses observed to be effective in human studies. For example, one human trial that showed improved insulin sensitivity with 1000 micrograms per day of chromium picolinate, showed subjects had an intake of chromium which ranged from 10 to 13 micrograms per kilogram. In this study using the rat model, total approximate daily chromium intake was greater than 30 micrograms per kilogram. The results of this study using the rat model are consistent with the limited human data that suggests that the chromium picolinate has a favorable effect in hyperinsulinemic or obese states (9).
What does the FDA have to say?
It is important to note that these studies examined persons with diagnosed type 2 diabetes. The majority of these studies demonstrate improved glycemic control with the additional supplementation of chromium picolinate. These studies discussed do not support claims for the prevention of type 2 diabetes. Nevertheless, there was a Qualified Health Claim (QHC) issued for diabetes prevention by the Food and Drug Administration (FDA) in 2005 (1).
The QHC is based on a study done by Cefalu et al in 1999. There were 29 subjects in the study who were at risk for type 2 diabetes because of obesity (subjects were above 125 percent ideal body weight) and family history of diabetes (subjects were required to have a first-degree relative with type 2 diabetes). The study was a double-blind, randomized, placebo-controlled trial lasting eight months in which subjects were divided into two groups. One group was provided with a nutritional regimen and used 1000 micrograms of chromium picolinate, while the other group was provided with the nutrition regimen only. The results of the study showed a significant increase in insulin sensitivity at four (midpoint) and eight months for the group supplementing with chromium picolinate, when compared to the nutrition only group. Furthermore, the group supplementing with chromium picolinate showed no significant body weight changes, demonstrate that chromium picolinate can enhance insulin sensitivity independent of changes in body weight. The group supplementing with chromium picolinate also showed a reduction in insulin levels and fasting insulin levels, but the reduction was not statistically significant. Moreover, 24-hour glucose profiles did not change throughout the study in the group supplementing with chromium picolinate. One limitation of this study was that it had a small sample size of 29 subjects (10).
The FDA’s claim statement therefore states the following: “One small study suggests that chromium picolinate may reduce the risk of insulin resistance, and therefore possibly may reduce the risk of type 2 diabetes. The FDA concluded, however, that the existence of such a relationship between chromium picolinate, and either insulin resistance or type 2 diabetes, is highly uncertain.” (11). Chromium picolinate, as a dietary supplement, has been deemed safe by the FDA, which also has stated that there is a lack of serious adverse effects reported in the literature (11).
Conclusion
Chromium picolinate demonstrated that it can improve insulin sensitivity and enhance glycemic control in patients with type 2 diabetes. It has a reduced cost compared to traditional treatment, and can also be useful as a complement to traditional treatments including oral hypoglycemic agents and insulin. The studies reviewed in this paper used chromium picolinate which was shown to be effective in improving glucose and insulin markers in an amount which ranged from 200 to 1000 mcg per day. Further research is needed to examine a more distinctive dosage of chromium picolinate for the improvement of glycemic control and insulin sensitivity.
References
1. Broadhurst CL, Domenico P. Clinical studies on chromium picolinate supplementation in diabetes mellitus – a review. Diabetes Technology & Therapeutics. 2006: 8(6):677-687
2. Shils, ME, Shike, M, Ross, AC, Caballero, B, Cousins, RJ. (2006). Modern nutrition in health and disease, tenth edition. Philadelphia: Lippincot Williams & Wilkins.
3. Ryan GJ, Wanko NS, Redman AR, Cook CB. Chromium as adjunctive treatment for type 2 diabetes. Ann Pharmacother. 2003;37:876-885.
4. Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr. 1998;17(6):548-555.
5. Anderson RA, Cheng N, Bryden NA; et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes. 1997;46:1786-1791.
6. Ghosh D, Bhattacharya B, Mukherjee B; et al. Role of chromium supplementation in Indians with type 2 diabetes mellitus. J Nutr Biochem. 2002;13:690-697.
7. Martin J, Wang ZQ, Zhang XH; et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care. 2006;29:1826-1832.
8. Kleefstra N, Houweling ST, Jansman, FG; et al. Chromium treatment has no effect in patients with poorly controlled, insulin treated type 2 diabetes in an obese western population. Diabetes Care. 2006;29:521-525.
9. Cefalu W.T., Wang Z.Q., Zhang, X.H., Baldor L.C., Russell, J.C. 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;132:1107-1114.
10. Cefalu WT, Bell-Farrow AD, Stegner J, et al. Effect of chromium picolinate on insulin sensitivity in vivo. J Trace Elem Exp Med. 1999;12:71–83.
11. Summary of Qualified Health Claims Subject to Enforcement Discretion: Qualified Claims about Diabetes. Available at: http://www.fda.gov/Food/LabelingNutrition/LabelClaims/QualifiedHealthClaims/ucm073992.htm#chromium. Accessed on December 3, 2009.
Visit Seth's site at www.sethbronheim.blogspot.com
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