Chromium Biochemistry In Brief:
The biologically active form of chromium is Cr(III). It was observed that rats fed on yeast could not process glucose, which was reversed by feeding chromium or Cr(III) or chromium-rich food1 and patients on prolonged total parenteral nutrition (TPN) developed insulin resistance which was reversed by chromium2. Diabetes patients tend to be deficient in chromium levels due to enhanced excretion of chromium3. Taken together these observations suggest a role for chromium in glucose metabolism.
Glucose tolerance factor (GTF) is a complex of various molecules including a 1500 Da chromium binding peptide of glycine, cysteine, glutamic and aspartic acid called low molecular weight Cr (LMWCr) binding substance. In plasma, transferrin acts as a carrier for chromium. Upon binding transferrin receptors on cell surface the chromium-transferrin complex is endocytosed into low pH vesicles where chromium is released. The freed chromium is then bound by LMWCr 4, converting it to a holopeptide.
Chromium potentiates insulin sensitivity and insulin-dependent signaling via two activities: the holopeptide LMWCr is thought to stimulate tyrosine kinase activity of insulin- bound active insulin receptors, with downstream activation of insulin receptor kinase and enhanced insulin action5. In addition, chromium inhibits phosphotyrosine phosphatase, which decreases insulin sensitivity6. Chromium may also stimulate insulin binding and internalization, increase insulin receptor number, and beta-cell sensitivity7.
Chromium is concentrated in the spleen, kidney, liver and bone8. Chromium deficiency occurs in the elderly, as the ability to absorb chromium is impaired 9. Chromium picolinate, a popular chromium source is reduced by ascorbates and thiols, with generation of reactive hydroxyl radicals that can cleave cellular DNA 10.
Role And Benefits Of Chromium In Various Diseases
Efficacy Of Chromium In Controlling Diabetes:
There is sufficient evidence for some efficacy of chromium in controlling diabetes. Low chromium levels often occur in patients with diabetes 11. Over 15 trials have found that chromium or Cr(III) reduces fasting blood glucose levels in patients with type I and II diabetes and improves insulin sensitivity in type II patients. 12
Oral intake of Cr (III) decreases insulin levels, and glycosylated hemoglobin (HbA1C). HbA 1c, plasma glucose (fasting glucose, 2-h glucose) and insulin (fasting and 2-h insulin) levels decreased in type II diabetes in a Chinese population upon chromium picolinate (CrP) treatment. 13
Insulin sensitivity increased in 10 days upon CrP (200 ug/day) treatment in another trial14, while 10 months of CrP (500 ug/day) treatment in 833 patients improved glucose metabolism and alleviated diabetes symptoms 15. Two randomized trials administered 100 ug/day chromium or Cr(III) to patients- one study found a 70% increase in insulin sensitivity of individuals with first-degree relatives suffering diabetes.16
The second study in type II diabetes patients showed that supplementation of chromium with sufonylurea increases glucose control and insulin sensitivity using the most reliable measure- the euglycemic-hyperinsulinemic clamp. Decrease in gain of body weight and visceral fat was noted 17.
Brewer’s yeast and Cr chloride significantly reduced fasting glucose (and 2h glucose), and the required dose required of antidiabetic drugs in a double-blind cross over, randomized trial involving 78 type II diabetes patients. 18
Another such study in 43 diabetes patients given placebo and brewer’s yeast without GTF over 16 months, showed decrease in blood glucose and insulin levels.19
A trial of 188 type II diabetes patients treated with jiangtangkang (which contains chromium) 20 for 2 months, showed decrease in fasting and post-meal glucose, and HbA1c.
Supplementing Cr(III) with biotin lowered fasting blood glucose and HbA1C levels in overweight or obese type II diabetes patients. 21
Benefits Of Chromium In Decreasing Triglyceride, Serum Cholesterol And HbA1c Levels:
High doses of chromium can decrease triglyceride, serum cholesterol (10% reduction) and HbA1c levels, while increasing HDL (2% increase) in diabetic patients 22. This effect is also seen in non-diabetic individuals, and in the elderly 23, including those suffering low nutrition status. Glucose metabolism was also improved in women with gestational diabetes at 4 or 8 ug/kg CrP 24, and in steroid-induced diabetes (steroid leads to chromium loss) at 600 ug/day25. A decrease in insulin and C-peptide levels was also reported in gestational diabetes.
What Does Chromium Content In Toenail Indicate?
In a large study, 33737 individuals were monitored for toenail content of chromium or Cr(III) levels, with incidence of heart disease over 7 years and an inverse relationship was noted 26. Another study 27 compared chromium content in toenail of 688 diabetic patients to 361 healthy individuals. The diabetic/healthy subject OR was 0.74 (95% CI 0.49–1.11; P= 0.18 for trend) and diabetic with cardiovascular disease/healthy OR was 0.45 (95% CI 0.24–0.84; P= 0.003 for trend). However there is no study on the effect of chromium on cardiovascular disease, or any evidence that toenail chromium content reflects body content of chromium.
Can Chromium Control Prediabetes?
Prediabetes (Glucose intolerance) and normal glucose tolerance:
Most evidence suggests chromium is not effective in controlling prediabetes. Among nine studies on glucose intolerance in prediabetics, only two studies by one group28 reported significant reduction in post-load glucose levels with Cr treatment. Glucose tolerance, triglyceride or cholesterol levels are not improved in elderly glucose intolerant patients 29. Fourteen studies showed no effect of Cr on post-load glucose levels in subjects with normal glucose tolerance.
Chromium And Lipid Metabolism:
In two studies, brewer’s yeast increased HDL cholesterol significantly in patients with type 2 diabetes30.
As already mentioned, high doses of chromium can decrease triglyceride and serum cholesterol by 10% while increasing HDL by 2% 31 in diabetic patients, and non-diabetic individuals suffering low nutrition status. Intake of chromium at 600 ug for 2 months increased HDL by 16% in patients on beta-blockers 32. Similarly an HDL increase of 21% was seen in atherosclerosis patients treated with 250 ug chromium daily in 7-16 months 33. This effect is not seen in prediabetics or individuals with normal glucose tolerance. In the latter study triglyceride levels were lower in treated patients compared to placebo (1.68 +/- 0.11 vs 2.10 +/- 0.14 nmol/L).34
In a study of type II diabetes patients, supplementing 1000 ug/day Cr(III) with sulfonylurea decreased free fatty acids (-0.2mmol/L vs. -0.12 mmol/L) as compared to placebo with sulfonylurea. However, triglycerides showed an opposite trend in this study. No statistically significant changes were seen in LDL cholesterol in any study35
Chromium For Weight Loss (Including Obesity), Fat Loss, And Lean Body Mass:
In a study of type II diabetes patients supplementing 1000 ug/day Cr(III) with sulfonylurea (n=17) lowered rate of fat accumulation (0.12% vs 1.17%), and gain in body weight (0.9 kg vs. 2.2 kg) as well as fat-free body mass (1.07 vs. 0.68) as compared to placebo with sulfonylurea (n=12), over 6 months.36
Chromium picolinate treatment at 200-400 ug/day in combination with strength training has been shown to induce weight loss (1.1-1.2kg over 10-13 weeks) and fat loss, with increase in lean body mass in some studies, even in the elderly, but the methodology used is questionable37. Other studies indicate no effect38.
One study provides tentative benefit of chromium in preventing weight gain upon cessation of cigarette smoking 39. Further studies are needed to resolve the effect of chromium on weight loss and gain of lean muscle mass 40.
Effects Of Chromium Picolinate In Treating Atypical Depression:
A small double-blind study in patients (n=15) suffering atypical depression found antidepressant activity of chromium picolinate in 70% patients, while placebo had no effect, over an 8 week treatment period. It is speculated that chromium picolinate may downregulate 5HT2A , or increase insulin sensitivity, resulting in antidepressant effects41 . A randomized, double-blind, multicenter study in patients with atypical depression (n=113) receiving 600 ug/day chromium picolinate or placebo showed improvement in carbohydrate craving and appetite regulation upon chromium treatment. It is suggested that studies with larger dose of chromium may affect mood 42.
Effectiveness Of Chromium Picolinate In Treating Dysthymia/Mild Depression:
There is tentative evidence that chromium picolinate or polynicotinate at 200 ug-400 ug/day may act as antidepressant. Only 5 patients were tested who were partial responders to psychiatric drugs nortrityline or sertraline 43.
Effectiveness Of Chromium In Treating Hypoglycemia:
200 ug chromium chloride treatment over 3 months alleviated hypoglycemia and increased serum glucose levels post-glucose load in hypoglycemic patients (n=8) in a double crossover study, with increase in insulin binding and insulin receptor number44. Chromium salts protect against cerebral injury and induce regeneration of cerebral tissues caused by hypoglycemic injury. Chromium appears to modulate transcription factors, neuroplasticity markers and glucose transporters45. However it should be noted that a case has been reported where hypoglycemia occurred upon fasting and insulin suppression which was reversed by withdrawing chromium supplements 46.
Effectiveness Of Chromium In Treating Polycystic Ovary Syndrome (PCOS):
Insulin resistance is commonly associated with PCOS. Insulin resistant women with PCOS have significantly increased fasting insulin and decreased serum levels of chromium 47. Obese women with PCOS were treated with chromium picolinate 1000 ug/day with 38% improvement in glucose disposal rate, using the euglycemic hyperinsulinemic clamp technique suggesting improved insulin sensitivity 48.
Benefits Of Chromium In Treating Turner’s Syndrome:
Turner’s syndrome is a genetic disorder with high incidence of diabetes. Patients suffering this syndrome (n=14) dosed with 30 g brewer’s yeast (50 ug of chromium) daily for 8 weeks showed improved glucose tolerance. In three patients with high cholesterol, a decrease in cholesterol and/or triglyceride levels with an increase in high-density lipoprotein cholesterol was noted 49.
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