Zinc is sometimes referred to as an insulin mimetic and just like insulin, has a good side and a not so good side, so does zinc – supplement wisely.
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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.
This week, we feature zinc
Zinc is the second most abundant trace element in the human body, after iron. In metabolic syndrome serum zinc levels may be marginally higher than normal initially, but they shift downward, as your body chemistry deteriorates.
The fact that they are up is not a BIG surprise.
Zinc and insulin are joined at the hip
When you are insulin resistant, the problem is not a shortage of insulin per se. The pancreas is churning out the stuff, morning, noon and night, unfortunately many cells are not responding appropriately to insulin, it is this “lack of response”, that makes you insulin resistant.
Zinc involved in the synthesis, storage and release of insulin.
And zinc is secreted along with insulin, from the secretory granules, by beta cells.
So when there is more insulin in the circulation, it follows that there will be more zinc in the circulation, because insulin and zinc are secreted together.
But, the actual amount of zinc in the circulation is tiny, it is in the nanomolar range. The zinc that matters, is the zinc inside cells, particularly the zinc levels in the cytoplasm.
NOTE : This means that serum zinc levels are not a good indicator of zinc status, because the body makes sure, they’re always about the same.
Shifts in this number only happen in serious circumstances such as
- “Bad” diet
- Infection e.g. COVID-19 ( it’s a consequence, not a cause)
- High sugar levels aka poor glycemic control
Low zinc diets
We only need 2-3 mg of zinc per day. Since it can be a bit tricky to get the zinc in, the Recommended Dietary Allowance has been set at 10 mg /day. People eating little to no animal protein, for an extended period of time, are most likely to be zinc deficient.
Zinc deficiency is very common in malnourished communities, where it is associated with a multitude of problems
- Impaired growth
- Reduced appetite
The other group of people, who are prone to dietary zinc deficiency are vegetarians/vegans and people eating a very high fibre diet.
NOTE : It’s not that plants do not have zinc, they do. It’s just that the zinc they have, is hard to access, because it is tightly bound to the plant.
During infections, the levels of Zn are deliberately reduced in serum and the “missing” zinc, is redistributed to tissues and immune cells as a part of “nutritional immunity”.
The “thinking” behind this, is to enhance immune cells’ function and make it hard for the disease causing organism, to get zinc, for it’s own growth and replication.
NOTE : Deliberately adding it back, may makes things worse not better. There is some evidence that zinc supplementation, in patients that have been hospitalized with COVID, hurts, rather than helps their recovery.
Bad body Chemistry
In diabetics serum zinc levels are often lower, this is as a result of increased loss in the urine , a condition referred to as hyperzincuria.
It turns out, as the sugar is lost, zinc goes with it.
The human body has somewhere between 2 and 3 g of zinc. It is found in all the tissues, but the pancreas and the bone, have particularly high levels. The high levels in the pancreas, are a reflection of the important role zinc plays in insulin’s biology.
A lot of body zinc is structural – around 3000 proteins have a zinc or two, somewhere in them. But some of it, is functional. Over 300 enzymes, use the zinc to DO what they do, so do multiple transcription factors.
But this is not the only reason why zinc SO IMPORTANT, it has a major regulatory role…
Transient changes in zinc levels, signal to cells….
The levels are changed by a family of transporters, which constantly move zinc around.
- There are the ZIPs (zinc/iron transporters) which move zinc into the cytoplasm. Humans have 14 different types.
- The ZnT (zinc transporters), that move zinc out of the cytoplasm. Humans have 10 different
The zinc in the cytoplasm is kept safe, by metallothionein proteins, which act as zinc buffer , humans have 4 different versions of this protein.
Keeping zinc SAFE
If a cell is challenged by a sudden influx of zinc ions, the free zinc ions will be shuttled onto metallothionein, so the zinc levels return to normal.
When zinc levels rise, this activates metal response element binding transcription factor (MTF-1). MTF-1 turns on genes that helps cells deal with metal toxicity.
And oxidative stress.
Plus, it triggers the production of more metallothionein.
NOTE : So levels of metallothonein are a better indicator of your zinc status, but currently this is not a test, which is available commercially.
Now when the beta cells pump out insulin, it doesn’t trickle out, it gets packaged into special secretory granules, along with a bunch of other things.
And the insulin is not GOOD TO GO.
The beta cells make pro-insulin, which gets cut up into bits and then is glued back together, in a maturation process.
The zinc is involved in insulin processing and packaging.
Insulin gets zinked
The zinc is moved into the secretory granule by the ZnT8 transporter. Lots of it. It’s estimated that the concentration of the zinc in the secretory granule can reach somewhere between 20 and 30 mM.
The mature insulin teams up with zinc and jumps into the hepatic portal vein.
The insulin that is made is a single insulin, in this form, it is referred to as a monomer. But, the insulin that is ultimately pushed out of the secretory granule, is a hexamer.
It is a conglomerate of 6 insulin molecules, held together by 2 zinc.
Zinc is a big boy
Now truth be told….. insulin can make the leap without zinc.
And sometimes it does.
Guinea pigs don’t have zinc accompany their insulin and they do just fine. Actually, some humans don’t have a working version of the ZnT8 transporter, others have a not so good version and they seem to do, okay. In fact, studies suggest they are protected from type 2 diabetes.
Too much zinc a risk for type 2 diabetes
No one knows for sure why they are better off, but it’s suspected it has more to do with what happens to amylin than insulin. But that’s a story for another day. Click here to learn more.
So zinc in this context, is not a must have……. it’s a nice to have.
Zinc the insulin mimetic
When all is said and done…………… insulin’s impact is enhanced by the zinc. Zinc has been described as an insulin mimetic.
And just like insulin it has a good side and a bad side.
Numerous studies have shown, zinc supplements improve glycemic control, especially in people with diabetes, this is shown by this forest plot.
The plot summarizes the results of 36 studies. The position of the dotted line shows overall zinc is helpful. Although not all studies reported benefits on fasting blood glucose.
So zinc is both essential and toxic.
Your body does have mechanisms to protect itself from TOO MUCH zinc. But it can and does accumulates over time.
Too much of a good thing, can be a bad thing.
Remember you only need 2-3 mg. And the RDA is 10 mg, climbing a little higher in special risk groups, such as pregnant women.
If you’re eating a plant based diet, you could potentially be short.
Although it is important to realize, in the Western world, many products are fortified with zinc, so even vegetarians probably are getting more than they might think.
Dietary sources of zinc
The best way to get it, is through your diet – you’ll get zinc from animal products.
- Oysters are zinc bombs, but an acquired taste and they are usually quite expensive.
- Red meat is the next best option
But it’s found in most animal products, so if you’re eating animal protein, you’re unlikely to need to take a zinc supplement.
Supplements may sometimes be necessary, if your diet is genuinely low in zinc.
But if you supplement, supplement wisely.
You do not want to get supraphysiological levels for an extended period of time, which is what you get if you take a 50 mg or 100 mg supplement, week in and week out.
NOTE : You must watch your copper intake, because zinc competes with copper for absorption, so if you ‘re supplementing with high doses of zinc, you can end up with a copper deficiency.
People who are diabetic often have a zinc dyshomeostasis, this is not due to a lack of zinc in their diet, but poor glycemic control.
Diabetics may benefit from a zinc supplement.
But, before sending more zinc, which can potentially be counterproductive, it would be wise to prioritize “fixing” the underlying body chemistry. Click here, to download with Willpower Report, it’s free, to discover 10 strategies, that will help, improve insulin resistance and glycemic control.
Here are a few of the journal articles I’ve used to tell the zinc story.
Relationship Between Serum Zinc Level and Metabolic Syndrome: A Meta-Analysis of Observational Studies. J Am Coll Nutr (2018 ) 37(8):708-715. Yi Zhang, Dian-Zhong Zhang.
Zinc and Insulin Resistance: Biochemical and Molecular Aspects. Biol Trace Elem Res (2018) 186(2):407-412. Kyria Jayanne Clímaco Cruz, Ana Raquel Soares de Oliveira, Jennifer Beatriz Silva Morais, Juliana Soares Severo, Priscyla Maria Vieira Mendes, Stéfany Rodrigues de Sousa Melo, Gustavo Santos de Sousa & Dilina do Nascimento Marreiro.
Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity. Int. J. Mol. Sci. (2018) 19 (2) : 476. Ayako Fukunaka and Yoshio Fujitani.
Metallothionein: a Potential Link in the Regulation of Zinc in Nutritional Immunity. Biol Trace Elem Res (2018) 182(1):1-13. Mohammad Tariqur Rahman & Muhammad Manjurul Karim.
Zinc in Cellular Regulation: The Nature and Significance of “Zinc Signals”. Int J Mol Sci (2017) 18(11):2285. Wolfgang Maret.
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