High dose chromium to fight glucose intolerance from rapamycin

For those of you that have experienced a worsening of glucose tolerance when taking rapamycin, has any of you tried taking very high doses of chromium in an attempt to minimize the negative effect on glucose tolerance?

Rapamycin supplementation in mice has been found to reduce GLUT-4 expression in their muscles. Rapamycin impairs HPD-induced beneficial effects on glucose homeostasis - PubMed See these two quotes from the full text:

“We also found that GLUT4 expression in muscle was significantly (P < 0.05) reduced in HFD-fed mice after 35 days of rapamycin treatment (Figure 6C).”

“The concentrations of chromium in the blood and bone of rapamycin-treated lean mice fed a HPD were approximately 34 and 33% lower (P < 0.05), respectively, in comparison with vehicle-treated animals, while the chromium concentrations in liver and fat pads exhibited the reverse trend, with mean increases of 2.1- and 1.8-fold respectively. However, a similar concentration of chromium was found in the muscle and kidney in the HPD control and HPD rapamycin groups. Our results thus demonstrated marked changes in chromium metabolism with a net movement of chromium in hyperglycaemic mice.”

Note that GLUT-4 is a transporter that transports glucose into muscles and other tissues. Lower expression of GLUT-4 would tend to worsen glucose tolerance. Interestingly in the above study, rapamycin influenced the distribution of chromium in the body of the mice, leading to reductions in the levels of chromium in the blood and bone while increasing it in their livers. Note that chromium is well known to be important for glucose uptake into tissues and it can improve glucose tolerance by increasing GLUT-4 translocation in cells. Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism - PubMed

This makes me wonder if high dose chromium might offset some of the negative effects of rapamycin on glucose tolerance, since rapamycin decreases GLUT-4 in some tissues while chromium increases it. While I don’t think it’s likely, I certainly think it would be an interesting experiment for people that notice worsening of glucose tolerance when taking rapamycin. Note that you might need very high doses to see effects. Studies have shown that people that are insulin resistant may need up to 1000 µcg of chromium daily to improve their blood glucose. Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium supplementation - PubMed

If anyone does this kind of experiment, please report back on your results, and note that it might take several weeks for the chromium to work.



I will revisit this supplement. I have just ordered some 1000mcg chromium picolinate after doing some research to find out if this high dose is safe.
My supplements or meds have not changed recently and my diet is fairly stable so I think it will be a fair test. My fasting glucose since restarting rapamycin is a little high.


Personally I’m very cautious about the dosage of chromium, from yesterday I began to take 200mcg chromium which should be 100mg chromium-enriched yeast 2000ppm, and I’m still afraid of chromium toxicity, since the recommended dosage is only 35 mcg for adult man, and 600 μg daily for 6 weeks has caused one case of renal failure, reference: Trace Elements and Metals - LiverTox - NCBI Bookshelf
Plus, From the reference above, I found this sentence: Systematic review identified 25 randomized controlled trials of chromium supplementation in diabetes concluded that chromium [in doses of 200-1000 μg daily] has favorable effects and does not increase the risk of adverse events above that of placebo).
I might be the over cautious type through.

I understand you wanting to be cautious here. Here are a few things to consider. Chromium has been given to mice in a lifespan study at a dose equivalent to more than 1000 µg daily for an adult human and it had beneficial effects on their health if I recall. Chromium picolinate is also sold in capsules up to 2000 µg in strength and 1000 µg pills have been sold for a long time and taken by thousands of people for long. With respect to the toxicity of chromium, hexavalent chromium is highly toxic and is known to cause kidney damage. However, chromium found in supplements is trivalent chromium, which unlike the hexavalent form is mostly not toxic. Recent developments in essentiality of trivalent chromium and toxicity of hexavalent chromium: Implications on human health and remediation strategies - ScienceDirect
I suspect that case report of that woman who suffered from renal failure sometime after having ingested chromium picolinate for a long period is explained by some kind of unusual contamination of the supplement perhaps with hexavalent chromium. However, if you want to be very careful, you can always ramp up the dose slowly and check your creatinine or cystatin C levels when you have increased it a lot.

Did you find a toxic dose?

No, I don’t know what the maximum safe dose is but you can find several studies that used 1000 mcg daily.
I found a study that it doesn’t probably doesn’t damage chromosomes.
I tried chromium picolinate several years ago at 100 mcg daily and it didn’t do anything that was detectable by me. I hope that 1000 mcg/day will have some effect on insulin sensitivity.

I think what I would do is a serum test for Chromium. It strikes me as something that excess could easily cause damage and hence I would want an idea as to whether I am arguably deficient first. I did this with Manganese and found I was not deficient so did not take any.

I would think Chromium is finely balanced as to the point at which chronic supplementation tips it over the top.

Thank you for this advice, especially the last sentence. I think currently I’d keep my 200 mcg chromium dose since before trying Rapamycin, I didn’t have any insulin issue, and now I take 500 mg metformin everyday if I don’t exercise a lot.

Supplementing in doses under 200 mcg did nothing for me so in light of recent studies I thought I would give it a try.

At 82 I have trouble keeping my fasting glucose below 100 and I am already taking metformin. I have tried adding Empagliflozin and other supplements that reputedly lower glucose levels and increase insulin sensitivity but oddly my fasting glucose levels remain in a range of 100 to 110 mg/dL. My doctor says I shouldn’t give a shite at my age but then the medical profession in general don’t care much about people my age as they see us with one foot in the grave anyways.

Supplementing with chromium at doses of 1000 mcg/day or less seems relatively safe and I get blood work done at least every two months now so I will keep an eye on my liver and kidney functions.

"Chromium monotherapy significantly reduced triglycerides and increased HDL-C levels. The effects on glucose and triglycerides levels were shown especially with chromium picolinate. Glycaemic control may improve with chromium monosupplementation of more than 200 μg daily. HbA1c and FPG also improved in patients with inadequate glycaemic control at baseline. The risk of adverse events did not differ between chromium and placebo."

Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes


FYI 200 µg daily also did nothing for me. I took that dose for years and it wasn’t until I increased my dose to 1000 µg daily that my blood glucose and insulin sensitivity became way better and has remained that way since.

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What magnitude of changes in fasting glucose, HbA1c, and fasting insulin (if available) did you have from taking 1000 mcg of chromium?

My postprandial blood glucose used to go close to 150 after eating meals containing lots of carbs but after upping my dose of chromium it usually stayed under 130 even when eating lots of carbs. Also an oral glucose tolerance test I took before increasing the dose of chromium showed that my blood glucose went up to 170 after drinking the glucose. Another such test I took years later after taking higher doses of chromium showed that my blood glucose didn’t even go above 100 after drinking the glucose, and that was despite my insulin not going up much at all.

I don’t know about HbA1c since I don’t have measures for that before I upped the dose. The fasting glucose also didn’t seem to change much but it wasn’t bad to begin with.