Tuesday, December 4, 2012

Chromium Picolinate Worsens Insulin Sensitivity in Healthy, Non-Diabetic, Non-Obese Individuals by Up to 25%

The more supplements you take the more likely you are to get way more than the 200mcg of chromium of which previous studies have shown that they are useless for healthy people, but at least not detrimental (cf. Lukaski 1996 & 2007; Vincent. 2007). Especially people who like the  'poly-supplementary' approach are yet at risk of getting so much of a this trace mineral that it will hamper not improve their insulin sensitivity.
I don't have to tell you that you would already be dead if you were following all the bro-scientific advice that's out there on the Internet and still I usually recognize a certain reluctance to give up on what X suggests and Y has tried an what has worked so well for Z. One of the instances, where I have hitherto been missing a 100% convincing argument to argue that this is just another instance where common wisdom would in fact be better called "common stupidity" is the "insulin mimetic" or "insulin sensitizer" (or whatever your favorite bro-expert may call it) chromium picolinate. With the recent publication of the result of a study on the effects of chromium supplementation in healthy individuals there is now finally a human study that confirms that chromium, which has never been an "insulin sensitizer", but rather an "insulin release amplifier" that reduced blood glucose in diabetics by simply having them produce even more insulin is not a supplement any healthy man or woman, let alone athlete should consider a staple of his or her regimen.

The long and short: Chromium hampers insulin sensitivity in normoglycemic individuals

For their experiment lead author Umesh Masharani and his colleagues from the UCSA recruited a group of 27 non-obese, non-diabetic, healthy subjects between the ages of 20 and 50 with a body mass index of less than 27 kg/m² and <24 kg/m² for subjects with Asian heritage (the cut-off limits were set so that they would be below a BMI that has not yet been shown to be an independent risk factor for insulin resistance; cf. Clausen. 1996; Newell-Morris. 1998).

To evaluate whether chromium picolinate (ChrPic) supplements, which contributed with $150,000,000 to the revenue of the supplement industry in 1996 (Nielsen. 1996), could come up to the claims that they would exert beneficial effects on glucose tolerance and insulin sensitivity, the study participants were randomized to take either a placebo or a high dose 500µg CrPic supplement twice daily for 4 months (the dosage was selected in view of previews studies reporting greater benefits of 1,000 vs. 200mcg of CrPic in - you already guessed it - diabetic subjects; cf. Morris. 2000).
Figure 1: Insulin sensitivity measured by euglycemic clamp before and after the 16 week intervention (left); change in insulin sensitivity of the individual subjects plotted against serum chromium levels at the end of the study (Masharani. 2012)
As the data in figure 1 goes to show, the results of the CrPic intervention were more or less the exact opposite of what the ~10 million US consumers of respective supplements probably expect from the pills many of them are taking almost religiously. Despite the fact that all subjects had very low chromium levels at the beginning of the study, the previously non-significant minimally benificial relation between both serum and urinary chromium, on the one hand, and insulin sensitivity (r = 0.24, p=0.1; r=0.08, p=0.79 respectively), on the other hand, had turned into a very significant negative correlation between high(er) urinary and serum chromium concentrations and lower insulin sensitivity at the end of the 16 week intervention period (figure 1, right).
"Due to the apparent variation in the degree of chromium absorption between subjects, we examined the relationship between serum chromium and change in insulin resistance. After controlling for baseline patient characteristics, results of a multiple regression analysis showed a strong association between serum chromium and worsening of insulin–mediated glucose disposal (β= -0.83, p<0.01), where subjects with the highest serum chromium had a decline in their insulin sensitivity. To further explore the association between chromium absorption and insulin resistance, patients within the chromium group were divided (based on  a medial split at 3.10 µg/L) into a high (n=6) and low (n=8) serum chromium group [...] There were no group differences at baseline; however, at post-assessment participants in the high serum chromium group (> 3.1  µg/L) were more insulin resistant than participants in the low serum chromium group (≤3.1  µg/L) or the placebo group (p=0.02, p=0.05 respectively) (Figure 3)." (my emphases in Masharani. 2012)
Due to the fact that the scientists did not observe any differences between the placebo and low serum  chromium groups (on a side note, contrary to many other studies insulin Masharani et al. measured the insulin sensitivity in a very reliable way with an euglycemic hyperinsulinemic clamp; cf. Defronzo. 1979), the scientists also conducted a post-hoc analysis to identify potential confounding factors that may have influenced the outcome of the trial. Neither changes in triglycerides levels LDL, BMI, or truncal fat were yet associated with the differences they observed between the supplemented and non-supplemented participants. Interactions that would reduce the significance of the observed correlations were likewise absent:
"Furthermore, when changes in triglycerides, LDL, BMI, and truncal fat were individually added to the model, none were independent significant predictors of change in insulin sensitivity, and chromium absorption remained a significant predictor of reduced insulin sensitivity in each model." (Masharani. 2012)
Against that background the scientists conclude that there must be a "direct effect of chromium on changes in insulin action". A mechanism, by the way, which is totally independent of classic markers of insulin resistance such as high serum lipids and abdominal / truncal adiposity .

Being healthy is a good predictor of increased chromium absorption and more pronounced negative effects, so if you are healthy and want to stay this way don't even think of taking high dose chromium supplements.

Despite the fact that the changes in insulin resistance did not depend on changes in serum lipids and other markers of metabolic health, Masharani and his colleagues were able to show that the increase in chromium levels in response to supplementation did. With the already mentioned statistically significant correlation between increases in serum chromium levels (higher response to supplementation = higher increase), on the one hand, and the worsening of insulin sensitivity, on the other hand, this means that the healthiest subjects, namely ...
"[...] subjects with lower triglycerides, and those with lower levels of homocysteine [who had] a greater likelihood of being in the high absorption group" (Masharani. 2012)
... were at the same time those who were at the greatest risk of the ill side-effects high dose chromium supplements exert on the insulin tolerance of healthy, non-diabetic, normal-weight individuals.

No matter if it may have helped you produce insulin back in your obese days, once you have accomplished this you better avoid high dose or multiple (hidden) sources of supplemental chromium like a plague - unless you can't afford new jeans, of course ;-)
Bottom line: Unless you are not a type II diabetic or feel the urgent desire to become one, you better steer clear of exuberant amounts of supplemental chromium the RDA is enough. This is particularly true, if you are already taking a multi (which is almost guaranteed to have 200mcg in it), or any BB-style supplements. After all, "broscience" wants it that chromium is in everything that's even remotely related to insulin / nutrient uptake or whatever. With the use of only one of these products and 200mcg of supplemental dietary chromium per day, you may still argue that it probably won't do much harm. When you add another 200mcg from your "nutrient partitioner" on top of the 200mcg you get from your multi and the 200mcg of which you probably did not even realize yet that they are part of your pre-workout supplement, however, you can hardly complain about simply not being able to tolerate carbohydrates - I mean, what's your body supposed to do if you are dumb enough to believe in the promises of fat loss and lean mass increases that have been debunked in the late 1990s, already (cf. Lukaski 1996 & 2007; Vincent. 2007), and simply chose to ignore the latest scientific evidence that chromium picolinate supplements are not just useless, but actually detrimental to your health?

  • Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K, Pedersen O. Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of  the impact of gender, body fat, physical fitness, and life-style factors.  J Clin Invest. 1996;  98(5):1195– 1209.
  • Defronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237:E214–E223. 
  • Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr. 1996 Jun;63(6):954-65.
  • Lukaski HC, Siders WA, Penland JG.  Chromium picolinate supplementation in women: effects on body weight, composition, and iron status. Nutrition. 2007; 23(3):187– 195.
  • Masharani U, Gjerde C, McCoy S, Maddux BA, Hessler D, Goldfine ID, Youngren JF. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocr Disord. 2012 Nov 30;12(1):31.
  • Morris BW, Kouta S, Robinson R, MacNeil S, Heller S. Chromium supplementation improves insulin resistance in patients with Type 2 diabetes mellitus.  DiabetMed. 2000; 17(9):684–685.
  • Newell-Morris LL, Treder RP, Shuman WP, Fujimoto WY. Fatness, fat distribution, and glucose tolerance in second-generation Japanese-American (Nisei) men. Am J Clin Nutr. 1989; 50(1):9–18.
  • Nielsen FH. Controversial Chromium: Does the superstar minearal of the mountebanks receive appropriate attention from clinicians and nutritionists?  Nutr Today. 1996; 31(6):226–233.
  • Vincent JB: The nutritional biochemistry of chromium (III). Amsterdam, Boston: Elsevier. 2007.


Primalkid said...

Just like ALA...

How does this relate to a whole foods diet? Is it just the supplement that worsens insulin sensitivity, or can you overload through natural sources as well?

Belgian Blue said...

It lowers sensitivity because it increases insulin. That doesn't make it bad, that places it squarely in the same category as carbohydrates. If there was a use for physiologically elevated doses of insulin, this could be a decent supplement. I grant you, I don't really see a particular use for insulin spikes in the physiological range, but to proclaim some sort of demonic supplement, or dangerous is a bit out there. A bit similar to the way you trashed zinc when its nutrient absorption increase also lead to metabolic disorders in a study on "healthy volunteers".

The conclusion of this study for the sport-minded individual should simply be that chromium enhances insulin secretion, it does not enhance insulin sensitivity, and if used, it should be used in such a context.

As apt as I deem your caveats to be that we shouldn't go by the results of overweight and diabetic subjects to judge the use for something, I think you are a bit too quick to use "healthy volunteers" as a good way to extrapolate usability to the athletic individual, who is infinitely less prone to metabolic disorders simply because he is more insulin sensitive and has more use for his calories/macronutrients.

majkinetor said...

100% agree with you.
Its his general tendency.

Several friends of mine and me experimented with Cr (various forms). We all found that it descries appetite for carbs tremendously. I don't even remember when I had carb cravings last time. Before that, it happened regularly. Appetite also goes down, and when you are hungry, you actually crave non-carb food.

Also, with absence of carbs and inclusion of Cr you boost your vitamin C absorption (as insulin promotes it). I find it a perfect way to make C more bioavailable.

Again, if we beleive like some scientists that most of the western population are in prediabetic state, we can only welcome Cr in ones supplementation protocol.

majkinetor said...

But in that magic window between 16-20 plus if you have no diabetes, no obesity, do not eat junk food, and so on.. hey, you don't need it for sure...

But then, you probably wont care during such time about health, but about emo stuff.

Prof. Dr. Andro said...

it may not make it bad, Belgian, but it does not make it beneficial either - and that's what I find annoying: It's hailed for benefits that are not there. Neither increases in muscle nor decreases in body fat.

It is also not correct that an athlete could use this kind of insulin increase for his advantage, because the downstream effects are the same, when you increase insulin but decrease the ssensitivity at the receptor level.

You are correct though that the "dangerous" label would be inadequate - I guess the undertone may have too much of a yellow press appeal "yellow press"

Chad said...

I'm sorry I'm late commenting on this, hopefully someone sees it, but I came across something interesting in my reading and I wanted to share it.

ChromeMate, the chromium supplement that was researched and many chromium claims are made based on, is actually chromium polynicotinate, not chromium picolinate. I am curious if this might have a different effect than the picolinate form, and perhaps, ChromeMate is actually beneficial. Any thoughts?

Prof. Dr. Andro said...

well, most of the actual research that's showing benefits is has been done with chormium + nicotinic acid

now you add Chr + NA = 2 agents good for diabetic obese people and bad for healthy lean ones... what may be the outcome in healthy lean people?

Just a an aside NA is liver-toxic, can have muscular sides similar to statins (at high doses) and impairs insulin sensitivity in normal young men => " In studies of healthy volunteers, immediate-release niacin (in doses up to 1000 mg/day) resulted in decreases in insulin sensitivity" - http://www.sciencedirect.com/science/article/pii/S1933287407001997

Chad said...

Thank you for the feedback Dr. Andro!

I guess where I get hung up is that a quick search on Google Scholar kicks up a ton of studies on chromium showing that it is effective OR no effect whatsoever, but then to see a study that suggests that it's actually detrimental, that surprises me.

Similarly, niacin is a very popular and widely used supplement. To see a study that says that it's not just ineffective but also harmful really hits me hard.

It is studies like these that often make me question supplementation in general and wonder if I should stop taking supplements all together. With so much contradictory information out there, it's very frustrating to be a consumer these days....

This is why I appreciate what you do here so much. Thank you!

Prof. Dr. Andro said...

well, both have beneficial effects in fat people. The increase insulin due to chromium (unnecessary for a healthy individual) can postpone the timepoint at which people will have to resort to insulin injections and niacin will lower blood lipids in the acute phase (not in the rebound phase, though) and in this time period the body is forced to use more glucose, which again can be beneficial for fat people.

bottom line: Don't use your fat neighbors supplements or medication. What may be good for him is rarely good for you as well.

Chad said...

That makes sense Dr. Andro, kind of like using medication I suppose, and I think that I, as well as other people, often look at supplements as just beneficial additions to our diets when we should really be considering them more like medication. I'm not diabetic, so I'd never think to use metaformin or insulin, but for whatever reason, I decided that using ChromeMate and ALA was a good idea. I would've been better off only taking what I need and nothing I don't. Thanks again!

Anonymous said...

Dr. Andro,

Why was this left out of your discussion? This is the paragraph from the study, "Insulin sensitivity (M LBM/I) did not significantly differ in the chromium and placebo groups at baseline (t= -0.22, p=0.83). After 16 weeks of therapy, the mean change in insulin sensitivity was -1.63 mg/min/kg/mU insulin (range: -8.9 to + 5.57) in the placebo group and -1.14 (-5.22 to + 4.11) in the chromium group (see Figure  1). The group x time interaction was not significant [F(1,22) = 0.36, p=.54] suggesting the degree of change in insulin sensitivity from pre- to post-assessment did not statistically differ by group. "

Adel aka Dr. Andro said...

the reason is that the point I am making is not about / against chromium supplemtation in general. It's probably even an essential nutrient. So the problem I was pointing my finger at is not taking chromium but adding it on top of a diet / basal supplementation due to which you are already in the normal (or >normal) range, where the same chromium someone with low levels may benefit from will suddenly turn against you. Check out the figure and my first citation in this post - both refer to "high chromium levels <> decrease in insulin sensitivity" not to "chromium supplementation <> decrease in insulin sensitivity"; if you take a bunch of supplements, you get plenty of it anyway, so for many of the SuppVersity readers taking additional supplements (let alone super-dosing, as I have seen some people advice others to do) could have the exact opposite effect of what they expect it to do.