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Uric acid in insulin resistance

Posted by Dr Sandy on in IR | 1201 Views | Leave a response
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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.

  • Sugar
  • Insulin
  • 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.

In this post, we feature uric acid.

When you’re insulin resistant, it’s typically up.

Sometimes, the levels are so high, as to precipitate an attack of gout.

Although, most of the time, this doesn’t happen.  Stats suggest that only around  5 % of people with levels > 6.5 mg/dL, suffer from gout.  This means,  you can have high uric acid levels (referred to as hyperuricemia) and have  no  obvious trouble.

But those high levels are still problematic.

Basic biochemical studies, suggest uric acid impacts glucose and lipid metabolism.  It is both a cause and consequence of  insulin resistance.

So what is uric acid ?

Uric acid is a metabolite i.e. it the final break down product of purine metabolism.

purine metabolic pathway

It circulates, in the blood in it’s ionized form i.e. urate.   Normal human levels range from 2.6 to 7.6 mg/dL.  Now,  these higher uric acid levels, are a pretty unique feature of humans and a couple of primates.

Uric acid is a trump card

Most animals, including rodents, actually have very little of it circulating, their blood levels are in the order of 0.5 – 2 mg/dL.

Now, just like us, they make it.

But, it turns out, they have an enzyme, that quickly breaks down the uric acid, to allantoin.  This is the enzyme that we’re missing, it is called URICASE.

The fact that we are missing it, is important – it’s part of what makes us SPECIAL.

comparison of uric acid levels in different creatures

So, although uric acid is seen as junk, it’s NOT.

The kidney keeps it

In fact, our kidney’s work hard to KEEP urate.  91-95 % of it is reabsorbed in the proximal tubule,  only,  3-10 % is pee-ed out.  But, when enough is not excreted,  the amount of uric acid, circulating, can reach a tipping  point, which sees, it start  start to form little crystals.

These crystals settle out…..and create TROUBLE.

Uric acid the trickster

The two places, they often end up………

Inside the joints where they cause gout and inside the kidneys, where they can cause kidney stones and negatively impact kidney function.

uric acid crystals getting up to mischief

So, uric acid is both good and bad.

Controlling the trickster

And as such, the body has a system in place to keep uric acid levels, JUST RIGHT.

Getting it JUST RIGHT, depends  on matching production to elimination.  Several factors can impair this balance, inducing hyperuricaemia.

juggling urate levels

Drugs

When it comes to drugs, there are quite a few, that can increase the odds, you develop hyperuricemia, usually because, they interfere with the ability of your kidney, to excrete the uric acid.   Among them

  • Diuretics
  • Low dose aspirin
  • Anti-TB mes

Genes

Each of us, has a unique collection of urate transporters, moving urates  in and out of the kidney.

urate transporters

Our genes, determine, just how efficiently this happens.

If you’re unlucky enough, to have inherited a “dicky” version of one of the urate transporters, your  capacity to move urate out, is going to be lower, making you more vulnerable to hyperuricemia.

Body Chemistry

Since insulin, impacts, urate transporter activity, suffering from hyperinsulinemia, puts you at a distinct disadvantage, so does any kind of kidney dysfunction.

If you, also produce more…. it’s easy to get into trouble.

So managing your uric acid pool,  is something that should be on your agenda, if you’re insulin resistant.  This can be done, with meds and lifestyle.

purine management

Urate lowering meds

In terms of meds, there are quite a few to choose from, the one with the most science behind it, is allopurinol.  Several studies, suggest, urate lowering meds, can  improve insulin resistance, in both mice and men.

But, before you jump in and get a prescription for one.

There is NO SCIENCE, suggesting this improved insulin resistance, translates to improved longevity.

NOTE : Urate is both a good guy and a bad buy, rolled into one.

Beyond pills

So if you’ve got asymptomatic hyperuricemia, swallowing a pill, is never going to be, the optimal solution.  Your best bet, fix the underlying body chemistry, as far as possible and  modify your lifestyle, so you make less uric acid.

If you want some help, getting started here, download our free Willpower Report, here. It introduces  you to the 10 weapons, you can use to Rein in insulin and thus, improve your insulin sensitivity, without meds.

Focus on purines

Uric acid is a purine breakdown product…… so, where do purines comes from ?

Well, you eat them.   Purines are found in virtually all foods.  As a rule, the more energy dense a food is, the more purines it is likely to contain, because it contains more cells.  And cells have DNA and RNA, plus energy in the form of ATP.

These molecules are all made of purine  nucleotides.

explaining the beer gout connectionNot the ones in real food

Cutting energy dense real food from your diet – is NOT going to serve you.

But the one thing, to cut from your diet is alcohol, especially beer.   Interestingly enough,  it’s probably NOT the alcohol in the beer, that is the problem, but the yeast, that is used to make the beer.

Beer is often cell dense.

Not the ones you need

In addition, to purines, you eat, your body, makes purines – you NEED them.  They used to make DNA and RNA, plus they form the basis of the cell’s energy currency, ATP.

But, having said that, there are a couple of chemical reactions,  create purines, as byproducts.

These are purines, you don’t NEED.  Since you don’t need, them they need to be processed and then excreted, and it is these extra purines, that are often associated with TROUBLE. It’s these purines, you want to go after.

Limit the production of extra purines

And the  biggest source of these purines, is excess sugar.  Fructose is the real, trouble maker, because when it is split, to access, it’s energy,  the reaction produces a  uric acid molecule.

But, before you get down on fructose, it’s worth remembering…..

Under the “right” circumstances, glucose can be turned into fructose.

fructose to uric acid pathway

And of course, if you’re insulin resistant, the odds that the circumstances are “right” for the fructose to glucose conversion, skyrocket.  Eish !

Limit liquid sugar

The excessive consumption of fructose, primarily in the form of sugar sweetened beverages, between meals,  is the most important inducer of hyperuricaemia.

Watch this video, to learn more about what LIQUID SUGAR, between meals, is particularly problematic.

So if you’re insulin resistant, cut back on table sugar and high fructose corn syrup, especially in the liquid form.

Uric acid,  is just one of hundreds of chemicals in the body that are amiss, if you’re suffering from metabolic syndrome.  Click here, t0 visit the “Ups and Downs of insulin resistance” page, to learn more about some of the other players.

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Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia.  J Investig Med (2015)  63: 924–929. Mumtaz Takir, Osman Kostek, Abdullah Ozkok, Omer Celal Elcioglu, Ali Bakan, Aybala Erek, Hasan HuseyinMutlu, Ozge Telci, Aysun Semerci, Ali Riza Odabas, Baris Afsar,  Gerard Smits,  Miguel ALanaspa,  Shailendra Sharma, Richard J. Johnson,  and Mehmet Kanbay.

Drug-induced hyperuricaemia and gout.   Rheumatology (2017) 56:679-688.  Ben Salem, Raoudha Slim, Neila Fathallah and Houssem Hmouda2doi:10.1093/rheumatology/kew293

The role of xanthine oxidoreductase and uric acid in metabolic syndrome. BBA – Molecular Basis of Disease (2018)  1864:2557–2565. Maria Giulia Battelli, Massimo Bortolotti, Letizia Polito, Andrea Bolognesi

Physiological functions and pathogenic potential of uric acid: A review. Journal of Advanced Research (2017) 8 :487–493. Rashika El Rid,  Hatem Tallima

Uric Acid as a Cause of the Metabolic Syndrome. Contrib Nephrol. (2018)   192 : 88–102. Christopher King, Miguel A. Lanaspa, Thomas Jensen, Dean R. Tolan,  L. Gabriela Sánchez-Lozada, Richard J. Johnson

Endogenous fructose production: what do we know and how relevant is it? Curr Opin Clin Nutr Metab Care (2019) 22:289–294. Ana Andres-Hernando, Richard J. Johnson, and Miguel A. Lanaspa

Further reading

kidney being squeezed by vasopressin

Rehydrate with water, it’s easier on your kidneys

Rehydrating with a cold drink, puts back the water, along with some sugar. The glucose is FUEL, but the fructose………is a challenge, for a dehydrated kidney.

fructose attacking big toe

Time to change what is out in gout ?

Gout is caused by eating too much meat and swigging back too much beer. Well that is what the health gurus and medical textbooks proclaim BUT…

fat sippy cup drinking juice

Juicing up is fattening up

If you crunch the numbers – a glass of apple juice can actually have a few more calories than a glass of cola. And those calories are not equal.

  

Want to discover more ways to create BETTER BODY CHEMISTRY ?

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Posted in IR | Tagged adenosine, fructose, gout, insulin resistance, kidney, metabolic syndrome, purines, urate, urate transporters, uric acid, uricase

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