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Insulin Resistance and The Case for Chromium

Insulin Resistance and The Case for Chromium

Now that the calorie and cholesterol hypotheses are dead, the great nutrient collapse is upon us and insulin resistance has taken center stage. Evidence abounds that chromium deficiency is a key factor in the insulin resistance epidemic, comprising conditions such as metabolic syndrome, diabetes, obesity, and polycystic ovarian syndrome (PCOS). Though the pathophysiology of insulin resistance can be understood by studying these conditions, chromium has been scientifically implicated as the required mineral cofactor in insulin sensitivity regulation, and so deserves more consideration.

But it’s challenging for conventional medicine to exploit the full potential of chromium for the target of insulin resistance. In other words, it’s difficult to make billions from chromium, though metal-based drugs may become a big part of future polyphamarcy. Evidence based medicine (EBM) in support of the health effects of chromium supplementation is in its infancy, in part because defined responses to trace minerals involve oxidation state and coordination chemistry, mechanisms which are not fully understood. (1) Chromium also may be less effective when combined with medications as opposed to by itself. Chromium cannot be patented, and it is one of the safest minerals on the planet, with little to any known side effects, which means it gets even less attention.

 

insulin

Suboptimal chromium intake

Widespread suboptimal chromium consumption likely fuels insulin resistance and its complications, such as cardiovascular disease. Adequate Intake (AI) levels of chromium have been established on the basis of chromium content in the Standard American Diet (SAD), which is anything but sufficient for optimal health.

In the US, the estimated average chromium intake ranges from 23-29 μg/day for adult women to 39-54 μg/day for adult men, which falls in line with established adequate chromium intake (AI) levels of 20-25 μg/day for adult women and 30-35 μg/day for adult men.

For example, when whole wheat flour is refined it loses about two-thirds of its chromium content (and that is a conservative estimate). (2,3) Moreover, a diet high in refined sugar can increase the excretion of chromium in the urine by as much as 300%. (4) One study suggests that monosaccharides, such as glucose and fructose, actually promote the excretion of chromium by the kidneys (the main way chromium leaves the body), thereby causing chromium levels to fall. (5)

Trace minerals are essential for properly functioning carbohydrate and lipid metabolism. (6) According to a 2016 study, the lower overall mineral intake, the higher the chances of coronary artery disease (CAD). (7)

chromium

A recent review study associates vitamin D, chromium and omega-3 deficiencies with insulin resistance. (8) A recent study showed that chromium when combined with magnesium improves insulin resistance more than either mineral alone. (9) In animals as well as humans (n = 3), chromium uptake when combined with vitamin C appears to be enhanced. (10,11) Interestingly, chromium deficiency is exacerbated by vanadium deficiency. (12)

What makes chromium so special?

Chromium, a ubiquitous and essential trace mineral, potentiates the action of insulin, thereby enhancing insulin sensitivity in tissues (primarily adipose, skeletal muscle, and liver). (13) Chromium basically rides shotgun with insulin (and potassium) to help push glucose into your muscle and fat cells, for the purposes of providing energy to cellular functions. The biologically active form of chromium, trivalent in nature, originally termed glucose tolerance factor (GTF), has been reported to be comprised of chromium, niacin, glycine, glutamic acid, and cysteine. (14)

Our chromium plasma levels have dramatically plummeted over time

There is approximately 1.5 mg of chromium in the human body. (15) In the 1980s and 1990s, chromium plasma levels ranged from 0.075 to 13 ng/ml. (16). Over the span of 37 yrs, from 1948 to 1985, mean chromium blood levels in the US decreased to anywhere from a factor of 215 to 7,692 times their original levels. (17) Although correlation indeed does not equal causation, is there any wonder we have an epidemic of insulin resistance on our hands?

Here’s how it works? Plants extract chromium from the soil and over time that soil becomes less and less replete with chromium. Modern agriculture knows that nitrogen, phosphorus, and potassium are required for the production of healthy plants, but little is known about chromium levels in soil. The dwindling levels of chromium in the soil coupled with Western diet and lifestyle likely are reflected by the fact that our mean chromium blood levels have dropped so dramatically over the last century.

 

chromiumplasmalevels

Source: Wallach JD, Lan M. Rare earths: forbidden curesBonita, CA: Double Happiness Pub.; 1996.

Conditions associated with chromium deficiency

Up to 70% of those who have impaired glucose tolerance are at risk of developing diabetes. (18) Some other conditions that chromium may be beneficial in preventing or treating include bipolar disorder, depression, dysthymia, hypertension, hypercholesterolemia, and reactive hypoglycemia. (19)

How dose chromium?

The European Food Safety Authority, in charge of providing dietary guidelines to the EU, has even concluded that chromium requirements cannot yet be established based on science. (20) The usual chromium dosage usually ranges from 200 to 1,000 μg/day, but it is advised that you consult your doctor. (21)

What is the best way to screen for chromium deficiency?

Chromium is concentrated in hair by a factor of ten in comparison to blood, suggesting that hair analysis is superior over blood for viewing chromium levels. (22)

The benefits of chromium

Chromium supplementation decreases fasting glucose, improves glucose tolerance, lowers insulin, and decreases total cholesterol and triglycerides while increasing HDL. (23)

Dietary chromium supplementation has been shown to produce beneficial outcomes against metabolic diseases beyond its nutritional effects (24,25). Risk of type 2 diabetes is lower in those who supplement with chromium. (26) A recent mouse study suggests that maternal chromium restriction diet results in glucose intolerance in male offspring by altering DNA methylation in insulin signaling pathways in mice livers. (27) The addition of chromium to humans lacking adequate amounts in their total parenteral nutrition (TPN) reversed conditions such as glucose intolerance, weight loss, peripheral neuropathy, and confusion. (28,29) A 1997 study found that fasting glucose concentrations were 15% to 19% improved in a randomized trial in China in those who took 1,000 μg/day of chromium picolinate as opposed to placebo. (30)

 

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Carbohydrates are metabolized by chromium in its trivalent state, thereby enhancing insulin signaling pathways and thus heightening insulin sensitivity. (31) A recent randomized controlled trial (RCT) found chromium reduces insulin resistance and stimulates ovulation in women with PCOS. (32) A recent mouse study suggested tissue chromium homeostasis disturbance in stroke rats with a net loss via urinary excretion, and found that daily chromium supplementation improved hyperglycemia and decrease glucagon and corticosterone plasma levels. (33)

In the poultry industry, chromium is used for muscle development, decreasing cholesterol, increasing HDL (the “good cholesterol) levels, and improving nutrient digestion. (34)

Rat studies have shown chromium to have antioxidant activity, by lowering tissue concentration of lipid peroxidation products. (35) Deficiency of chromium, and hence, its antioxidant activity, is known to disrupt carbohydrate and protein metabolism. (36)

Chromium also modulates brain serotonin function, suggesting potential psychiatric benefit. (37)

Chromium and Adipogenesis

The likely link between diabetes and obesity is the adipose tissue. The adipose tissue stores energy as triglycerides and it also releases free fatty acids. Chromium has promise in the future of antidiabetic medicine as it enhances insulin activity during adipogenesis. (38)

Foods highest in chromium

Chromium levels, although highly variable, are rarely measured accurately in foods. Some of the foods highest in chromium included whole grains, beef, chicken, lobster, shrimp, nuts, legumes, broccoli, bananas, mushrooms, cheese, and egg yolk.

Chromium is extremely safe

There is no toxicity associated with excess trivalent chromium intake, which is the form found in food and supplements, so the Food and Nutrition Board (FNB) of the Institute of Medicine has set no tolerable chromium upper intake level (UL).

Conclusion

In conclusion, it can be said that there is a case for chromium, especially in light of the worldwide insulin resistance epidemic, and further research is warranted. Correlation may not be equal to causation, but how long do you want to wait before science confirms which side chromium deficiency falls on? In light of the great nutrient collapse, I think that a compelling case can be made that chromium deficiency is a significant factor in the insulin resistance epidemic.

Resources:

  1. Panchal SK, Wanyonyi S, Brown L. Selenium, vanadium, and chromium as micronutrients to improve metabolic syndromeCurrent Hypertension Reports. 2017;19(3).
  2. Schroeder HA. Losses of vitamins and trace minerals resulting from processing and preservation of foodsAm J Clin Nutr.1971;24:562–573.
  3. Schroeder HA. The role of chromium in mammalian nutritionAm J Clin Nutr. 1968;21:230–244.
  4. Kozlovsky AS, Moser PB, Reiser S, Anderson RA. Effects of diets high in simple sugars on urinary chromium lossesMetabolism. 1986;35:515–518.
  5. Lukaski HC. Chromium as a supplementAnnu Rev Nutr. 1999;19:279-302.
  6. Panchal SK, Wanyonyi S, Brown L. Selenium, vanadium, and chromium as micronutrients to improve metabolic syndromeCurrent Hypertension Reports. 2017;19(3).
  7. Mahalle N, Garg M, Naik S, et al. Association of dietary factors with severity of coronary artery diseaseClinical Nutrition ESPEN. 2016;15:75-79.
  8. Faghfoori Z, Fazelian S, Shadnoush M, et al. Nutritional management in women with polycystic ovary syndrome: A review studyDiabetes Metab Syndr. 2017;Apr 5;S1871-4021(17)30011-5.
  9. Dou M, Ma Y, Ma AG, et al. Combined chromium and magnesium decreases insulin resistance more effectively than either aloneAsia Pac J Clin Nutr. 2016;25(4):747-753.
  10. Ross AC. Modern nutrition in health and disease. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2014.
  11. 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.
  12. Wallach JD, Lan M. Rare earths: forbidden curesBonita, CA: Double Happiness Pub.; 1996.
  13. Tsave O, Yavropoulou M, Kafantari M, et al. The adipogenic potential of Cr(III). A molecular approach exemplifying metal-induced enhancement of insulin mimesis in diabetes mellitus IIJournal of Inorganic Biochemistry. 2016;163:323-331.
  14. Toepfer EW, Mertz W, Polansky MM, et al. Preparation of chromium-containing material of glucose tolerance factor activity from brewer’s yeast extracts and by synthesisJ Agric Food Chem. 1977;25:162–166.
  15. Wallach JD, Lan M. Rare earths: forbidden curesBonita, CA: Double Happiness Pub.; 1996.
  16. Wallach JD, Lan M. Rare earths: forbidden curesBonita, CA: Double Happiness Pub.; 1996.
  17. Wallach JD, Lan M. Rare earths: forbidden curesBonita, CA: Double Happiness Pub.; 1996.
  18. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007;30(3):753-759.
  19. Gaby AR. Nutritional medicine. Concord, N.H.: Fritz Perlberg Publishing; 2011.
  20. European Food Safety Authority (EFSA) Panel on Dietetic Products NaA. Scientific Opinion on Dietary Reference Values for chromiumEFSA Journal. 2014;12(10). Accessed 9/12/17.
  21. Gaby AR. Nutritional medicine. Concord, N.H.: Fritz Perlberg Publishing; 2011.
  22. Wallach JD, Lan M. Rare earths: forbidden curesBonita, CA: Double Happiness Pub.; 1996.
  23. Pizzorno JE, Murray MT, Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. St. Louis, MO: Churchill Livingstone; 2016.
  24. Chen WY, Mao FC, Liu CH, et al. Chromium supplementation improved post-stroke brain infarction and hyperglycemiaMetab Brain Dis. 2016;31(2):289-97.
  25. Jamilian M, Asemi Z. Chromium Supplementation and the Effects on Metabolic Status in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Nutr Metab. 2015;67(1):42-8.
  26. Mciver DJ, Grizales AM, Brownstein JS, Goldfine AB. Risk of type 2 diabetes Is lower in US adults taking chromium-containing supplementsJ Nutr. 2015;145(12):2675-82.
  27. Zhang Q, Sun X, Xiao X, et al. Dietary chromium restriction of pregnant mice changes the methylation status of hepatic genes involved with insulin signaling in adult male offspringPLoS ONE. 2017;12(1):e0169889.
  28. JeeJeebhoy KN, Chu RC, Marliss EB, et al. Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutritionAm J Clin Nutr. 1977;30:531–538.
  29. Freund H, Atamian S, Fischer JE. Chromium deficiency during total parenteral nutritionJAMA. 1979;241:496–498.
  30. Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetesDiabetes. 1997;46(11):1786-1791.
  31. Tsave O, Yavropoulou M, Kafantari M, et al. The adipogenic potential of Cr(III). A molecular approach exemplifying metal-induced enhancement of insulin mimesis in diabetes mellitus IIJournal of Inorganic Biochemistry. 2016;163:323-331.
  32. Ashoush S, Abou-gamrah A, Bayoumy H, Othman N. Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trialJ Obstet Gynaecol Res. 2016;42(3):279-85.
  33. Chen WY, Mao FC, Liu CH, et al. Chromium supplementation improved post-stroke brain infarction and hyperglycemiaMetab Brain Dis. 2016;31(2):289-97.
  34. Haq Z, Jain RK, Khan N, et al. Recent advances in role of chromium and its antioxidant combinations in poultry nutrition: A reviewVet World. 2016;9(12):1392-1399.
  35. Preuss HG, Grojec PL, Lieberman S, Anderson RA. Effects of different chromium compounds on blood pressure and lipid peroxidation in spontaneously hypertensive ratsClin Nephrol. 1997;47:325–330.
  36. Haq Z, Jain RK, Khan N, et al. Recent advances in role of chromium and its antioxidant combinations in poultry nutrition: A reviewVet World. 2016;9(12):1392-1399.
  37. Attenburrow MJ, Odontiadis J, Murray BJ, et al. Chromium treatment decreases the sensitivity of 5-HT2A receptorsPsychopharmacology. 2002;159:432–436.
  38. Tsave O, Yavropoulou M, Kafantari M, et al. The adipogenic potential of Cr(III). A molecular approach exemplifying metal-induced enhancement of insulin mimesis in diabetes mellitus IIJournal of Inorganic Biochemistry. 2016;163:323-331.