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When you’re insulin resistant, that is, you’ve got metabolic syndrome, pretty much every chemical in the body is NOT QUITE RIGHT. Some are up. Some are down. Few are actually at physiologically NORMAL levels.
Traditionally the focus is on the big guns.
- And cholesterol
In this series, we take a look at some of the other players.
Who they are, what they’re up to and how they’re part of the state of insulin resistance.
Carnosine when you’re insulin resistant
Carnosine levels are down, specifically in type II fiber, predominant muscles, in someone with metabolic problems.
This problem does not happen in type 1 diabetics, implicating insulin in the process
The chemical name for carnosine is ?-alanyl-L-histidine. It’s a histidine dipeptide i.e. it is a tiny molecule, made up of two amino acids, L-histidine and beta-alanine, joined together.
It’s not the only histidine dipeptide, there are others, but it’s the one, WE HUMANS use.
The amino acids are stuck together, by an enzyme, called carnosine synthase.
Muscles are full of carnosine.
The other place, chock full of the stuff, is the olfactory bulb, these are the nerves that smell things. But, quite a few other cell types, can and do, make carnosine, including the kidneys, where the carnosine is nephro-protective.
The carnosine bomber
Carnosine is NOT found in your blood, except immediately after dinner, because we have an enzyme, serum carnosinase, which pulls it apart.
The presence of this enzyme, makes us, rather special.
Rats and mice don’t have it. This means, studies done in rats and mice, might not always, be relevant for humans.
Now, when it comes to this enzyme……. there are differences.
The life and times of carnosinase
- Some people don’t have it, at all……………..this mutation, lands them in heaps of trouble. Carnosinemia (carnosine in the blood), is associated with mental retardation.
- Some people are blessed with a “slow” version of the enzyme, they’re more likely to be great power athletes and less likely to suffer from nerphropathy, should they become diabetic.
NOTE : Carnosine is the kidney is nephro-protective, i.e. it protects the kidneys.
How active your carosinase is, doesn’t just depend on genes, your body chemistry, changes the enzyme’s behaviour. Unfortunately, high sugar levels, get it going, which is probably one of the reasons, hyperglycemia, goes hand in hand, with kidney troubles.
Carnosine is a nutrient
Now despite the presence of a carnosine bomber, we do still get some from out diet.
When we eat muscle meats, we can tap into the animal’s carnosine supplies.
Directly, or indirectly, because muscle cells are able to take up the raw ingredients and put them back together as carnosine.
So what does the carnosine do, inside the muscle ?
Carnosine the muscle maximizer
It does quite a few things………
One of the things it does, is to buffer the pH.
Exercising muscles generate protons. This acid interferes with their function. The imidizaole ring on the carnosine, is able to mop up the hydrogen ions. This keeps the pH, in a comfortable range, so muscles can keep going for longer.
Now, this is important, proton stress is an issue, for all muscles, muscles plagued by metabolic issues, are no exception. In fact, they’re probably a little more vulnerable, to proton stress, but the pH buffering effect, is not the reason, carnosine is making an appearance on the ups and downs, of insulin resistance series.
Numerous studies, suggest, supplementing with canosine, can improve glycemic control.
And better sugar control, is central to BETTER BODY CHEMISTRY.
So, how does carnosine do this ?
Carnosine improves glycemic control
Well to be honest, no one knows for sure, but one of the suggestions, is, it acts as a local histidine reservoir. Since histidine is an essential amino acid i.e. you cannot make it, this is most helpful.
What happens, is when muscles contract, they end up pushing carnosine out.
The carnosinase, quickly swoops in, creating L-histidine and beta-alanine. The beta-alanine, just hangs around, but the L-histidine, is subject to a decarboxylation reaction.
The carboxyl group, is pulled off – creating histamine.
The histamine, then hops on histamine receptors, that are on the blood vessels, running through the muscles.
The histamine hit
In response, the blood vessels, dilate.
Whoohoo……………… this improves supplies, to the exercising muscle.
- More oxygen,.
- More insulin – this makes you more insulin sensitive
- More sugar.
And you get better glycemic control.
Which is why, if you’re insulin resistant, getting carnosine levels, up, is going to be helpful. And, it’s really easy to do…
Load up with carnosine
The natural approach is to eat it, by eating “muscle” i.e. animal protein, on a regular basis. Red meat, chicken, fish, it doesn’t matter – they’ve all got histidine dipeptides in them, although they don’t always have carnosine.
Or failing this, consider taking a beta alanine supplement.
Supplementing for more carnosine
Why beta alanine, not carnosine ? Remember the carnosinase “bomber” – in two twos, the carnosine will be L-histidine and beta alanine. It turns out, muscles decide how much carnosine to make, based on how much beta alanine is around.
So sending more of this in, is optimal.
The good news, you don’t have to do it for long.
Current guidelines, suggest athletes, wanting to boost their sporting performance, take 500 mg for 4 weeks. That’s enough to get the levels, high enough to make a difference.
Beware of too much
You do want to be careful, don’t take too much, in one go. A “nasty” side effect, of big doses of beta alanine, is tingling skin (paraesthesia). It only, happens when you take a big amount, all in one go.
So if you’re insulin resistant, get those carnosine levels up – it’s help you muscles keep going, by mopping up protons and improving deliveries.
Carnosine is just one of hundreds of chemicals in the body that are amiss when you’re suffering from metabolic syndrome. To learn more about some of the other players, go to our “Ups and Downs” of Insulin Resistance series.
Here are a few of the journal articles I’ve used to tell the carnosine story.
Reduced muscle carnosine content in type 2, but not in type 1 diabetic patients. Amino Acids (2012) 43:21–24. Bruno Gualano, Inge Everaert, Sanne Stegen, Guilherme Giannini Artioli, Youri Taes, Hamilton Roschel, Eric Achten, Maria Concepcio´n Otaduy, Antonio Herbert Lancha Junior, Roger Harris, Wim Derave
Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid–base regulation of skeletal muscle. Comp Biochem Phys (2019) 234:77-86. Eimear Dolan, Bryan Saunders, Roger Charles Harris, Jose Eduardo Pereira Wilken Bicudo, David John Bishop, Craig Sale, Bruno Gualano
The Intriguing Role of Histamine in Exercise Responses. Exerc Sport Sci Rev. (2017) 45(1): 16–23. Meredith J. Luttrell and John R. Halliwill
Can the Skeletal Muscle Carnosine Response to Beta-Alanine Supplementation Be Optimized? Frontiers in Nutrition (2019) vol 6 article 135. Pedro Perim, Felipe Miguel Marticorena, Felipe Ribeir, Gabriel Barreto, Nathan Gobbi, Chad Kerksick, Eimear Dolan and Bryan Saunders
L-Carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products and tumor necrosis factor alpha levels in patients with type 2 diabetes: A double-blind placebo-controlled randomized clinical trial. Nutr Res. (2018) 49:96-106. Shiva Houjeghan1, Sorayya Kheirouri, Esmaeil Faraji,Mohammad Asghari Jafarabadi.
Teens with metabolic syndrome, that are not obese are slightly muscle deficient. Obese teens also have low muscle mass – suggesting metabolic syndrome is a muscle thing
Insulin needs wide blood vessels to work, but widening blood vessels causes blood pressure to drop – the carotid body, keeps things in balance. Hopefully.
In the insulin resistant, its thought that insulin arrives at the cell’s glucose gate, but the gate doesn’t open. What if insulin never makes it to the gate ?