Toxicity of insulin due to phenol and metacresol

[bvanant]

Hi there @bvanant - It looks like at least part of your post is from some sort of paper or article. Could you please post a link to the source information? Many thanks.

1. Kang S, Creagh FM, Peters JR et al. (1991) Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type 1 diabetic subjects. Diabetes Care 14: 571±577
   

 

[DCUKMod]

1. Kang S, Creagh FM, Peters JR et al. (1991) Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type 1 diabetic subjects. Diabetes Care 14: 571±577

Could you please post a hyperlink to it. Members like to read full papers in these circumstances.

 

[bvanant]

As far as I know this is not a free publication.
Sorry
BVA

 

[NicoleC1971]

I was searching for an insulin that has less phenol and/or m-cresol and I found none, regardles of application method (injection, CSII, IV). No wonder why ghe risk of cancer in diabetic patients is incerased.

That is an association that gives no proof of a cause and whilst I have heard that excess blood glucose may be linked to aiding and abetting cancer cells, I have not heard that it has anything to do with toxic substances in insulin. Either way I try to take as little of it as possible.

 

[LoriM]

I'm surprised how many people get upset over asking basic questions. I did a google search on cresol and phenols and wound up here. As a diabetic with multiple sensitivities, I'd at least like to know whether insulins are available that do not have those toxins in them. It's a fair question!
No one is saying they'd rather die, or complain... but I think wondering what else is in my insulin is worth asking. Now since apparently all but inhaled insulins have cresol, is there a brand that has less than the others? Over time, the exposure adds up--so I'd vote for less exposure. I think there was a chart somewhere that showed that Novalog has less cresol than Humalog. (can't find the chart). Does anyone have an answer for this?
And then... oh gosh... how to explain to my Kaiser doctor that I would be wanting to change brands to get just a tiny bit LESS poison into my system.

 

[ickihun]

Hi everyone,
I was wondering if anyone here was thinking about toxic substances present in insulin formulations. For example, Novorapid contains 1.5 mg/ml of phenol and 1.72 mg/ml of metacresol. Both of these substances are very toxic, and for someone who is injecting 20 units of insulin per day, means also 300 ppm of phenol per day and 344 ppm of m-cresol.
Here is the study that was dealing with cell death induced with these substances.
http://www.sciencedirect.com/science/article/pii/S2214750014001541
On the other hand, I understand that for the purification step, in the production of insulin, phenol is used to separate protein from DNA, but there must be an alternative which is safer.

I wonder if that's why over a certain dosage of insulin I'm getting water/bloating under my skin, on my stomach. Where I inject.
I am awaiting an op date for a bariatric bypass so I'll need less insulin. Taking triple strength 80units of basal and 3x 25units of novarapid.
No solution other than natural is safest but some of us have no choice.

 

[LoriM]

I did a rookie experiment on my own, against the strong advice of my pharmacist. I extracted half a vial of insulin and left it out in a lightly covered measuring cup... to see whether and how long it would take for the smell to dissipate (and thus the phenols and cresol). After two days the smell was almost gone, but so was the insulin. So... that idea is out.

 

[ickihun]

I did a rookie experiment on my own, against the strong advice of my pharmacist. I extracted half a vial of insulin and left it out in a lightly covered measuring cup... to see whether and how long it would take for the smell to dissipate (and thus the phenols and cresol). After two days the smell was almost gone, but so was the insulin. So... that idea is out.

I'm sure even the new insulins are trialled and tested before they are passed as safe.
Toujeo300 hasn't caused me any trouble but higher doses of novarapid make my swollen stomach far worse. Since reducing my doses the swellings are nearly gone but as a certain stage my stomach acted like a water bed. Very liquid filled.

 

[JAT1]

Very interesting discussion and another excellent reason to keep the amount of insulin injected to the least possible and concentrate on carb reduction. It doesn't worry me that the insulin I take has a toxic component. After all, the air I breathe, the water I drink and the food I eat are all polluted.

 

[ickihun]

It looks like I may have more than IBS problem again. Small swellings but very very upset tummy with pains. Constantly leaking from everywhere. Ha ha Similiar to food poison but not as ferocious. Maybe due to strong painkillers though. Swellings may not be from insulin after all. I'll keep you posted. Will have to see GP tomorrow Today I just want to sleep.

 

[JAT1]

It looks like I may have more than IBS problem again. Small swellings but very very upset tummy with pains. Constantly leaking from everywhere. Ha ha Similiar to food poison but not as ferocious. Maybe due to strong painkillers though. Swellings may not be from insulin after all. I'll keep you posted. Will have to see GP tomorrow Today I just want to sleep.[/QUOT

It looks like I may have more than IBS problem again. Small swellings but very very upset tummy with pains. Constantly leaking from everywhere. Ha ha Similiar to food poison but not as ferocious. Maybe due to strong painkillers though. Swellings may not be from insulin after all. I'll keep you posted. Will have to see GP tomorrow Today I just want to sleep.

I hope your GP gives you good advice and that you feel better soon! Sweet dreams!

 

[JAT1]

Somehow my reply got stuck in the quote above. Hope you get better soon !

 

[urbanracer]

I had been experiencing increasingly severe pains around the shoulder areas for over a year. Having read somewhere that diabetics have a higher incidence of frozen shoulder I assumed the muscle pains were related. Then around January time this year I also started to experience systemic rashes and anaphylaxis although I was not aware of changes in levels of exposure to a substance. I was taking up to 4 antihistamines a day (under doctor's orders I might add) to keep the allergy suppressed.

Reading through the PIL that comes with Mix25 and subsequently Abasaglar, I noticed that 1 in 10,000 users are likely to experience rashes and myalgia. After a discussion with an Endo' I got my basal changed to Levimir around September time and now here we are in mid-December and I am (almost) pain free and the systemic rashes have almost stopped.

A dermatologist previously dismissed the insulin as a trigger because I couldn't specifically confirm that reactions were occurring at injection sites. Strangely, I am now getting a clear reaction at the injection site from Levimir but the systemic rashes are not so bad.

This all started after taking insulin for 3 years without any issues, so have I simply built up a level of sensitivity to the bad stuff that's in insulin? It looks as though the drugs which are keeping me alive are also my worst enemy.

 

[ickihun]

I had been experiencing increasingly severe pains around the shoulder areas for over a year. Having read somewhere that diabetics have a higher incidence of frozen shoulder I assumed the muscle pains were related. Then around January time this year I also started to experience systemic rashes and anaphylaxis although I was not aware of changes in levels of exposure to a substance. I was taking up to 4 antihistamines a day (under doctor's orders I might add) to keep the allergy suppressed.

Reading through the PIL that comes with Mix25 and subsequently Abasaglar, I noticed that 1 in 10,000 users are likely to experience rashes and myalgia. After a discussion with an Endo' I got my basal changed to Levimir around September time and now here we are in mid-December and I am (almost) pain free and the systemic rashes have almost stopped.

A dermatologist previously dismissed the insulin as a trigger because I couldn't specifically confirm that reactions were occurring at injection sites. Strangely, I am now getting a clear reaction at the injection site from Levimir but the systemic rashes are not so bad.

This all started after taking insulin for 3 years without any issues, so have I simply built up a level of sensitivity to the bad stuff that's in insulin? It looks as though the drugs which are keeping me alive are also my worst enemy.

Definitely not off a statin then? They are renound for causing limb problems and weakness mind. I bet you've already aliminated those though, right?

My bloating was definitely a bad case of IBS although I cancelled my GP appointment I'm much much more less in cramping, spasming pain on my full dose of blood sugar raising mebeverine tablets. With occasional immodium tablets to stop the more immediate effects. I was in huge gut wrench labour like pain. I even suspected food poisoning at first.
The bloating came first though so it's easy to assume, for me, it's the whopper of insulin units injected there. Thankful it looks like I may be wrong.

 

[LizLola]

Phenols are toxic. And we have them inside our bodies all the time, as we inject and have wells of insulin or have pumps. Phenols were banned as preservatives in labs decades ago. i know a Swedish scientist who has invented a filter for insulin needles that would filter out the excipients on injection - we'd get the insulin, but not the phenol. Even for suspended insulin. So YES, there is something that can be done about it. However, the pharmaceutical companies weren't interested in protecting us.

 

[Jaylee]

Phenols are toxic. And we have them inside our bodies all the time, as we inject and have wells of insulin or have pumps. Phenols were banned as preservatives in labs decades ago. i know a Swedish scientist who has invented a filter for insulin needles that would filter out the excipients on injection - we'd get the insulin, but not the phenol. Even for suspended insulin. So YES, there is something that can be done about it. However, the pharmaceutical companies weren't interested in protecting us.

Hi,

Do you have any source links regarding the "filter?" Sounds facinating...

 

[JMK1954]

Yes, anything that may improve the life of any one of us should be taken seriously.

 

[bvanant]

A discussion of how a zeolite COULD be used as a filter to remove phenol. There is increasing evidence that phenolic preservatives might lead to premature site loss for pump patients i.e. unexplained hyperglycemia. Certainly there is evidence that phenolics can cause tissue irritation even in the absence of insulin so removing phenol during pumping might be helpful if you could figure out how to do it. But you need the phenol in the vial, insulin is a good growth medium for bacteria and in spite of some earlier comments earlier in this thread there are no other good enough preservatives that don't interact with the insulin.

BVA

 

[bvanant]

The article is by Hakan Erikson (the forum thinks the link is spam) at Lund. You can see it at Biotechnology Techniques, 1998 p 329. The fact that the paper is 22 years old and no products have appeared in that time frame suggests that perhaps it is not as trivial as it might seem

 

[ert]

Wow. This makes for cheerful reading. I didn't even know that Insulin formulations are cytotoxic in vitro; or toxicity is caused by the excipients phonel and m-cresol; or the toxic effects of excipients might explain inflammation of infusion sites in vivo. So this is all news to me.

Here's a good article I found: https://www.sciencedirect.com/science/article/pii/S2214750014001541
Download the pdf for free.

So it may be useful to know if you're on a pump and have issues of inflammation at the cannula site.