Minerals... Chelation & Bioavailability

Myriads of people all over the world supplement their diets with macro and trace minerals. When our diet is lacking in these important nutrients, health issues ensue, and it becomes a very good idea to consume a non-food mineral source. There’s only one catch… how do we know the minerals are going to end up where we want them to end up in our bodies? Just because you swallow a mineral doesn’t necessarily mean it’s going to go where it’s supposed to. This is one of the great dilemmas of human physiology and nutrition. Now if there were only a liaison, a chaperone if you will, that escorted the minerals to where they needed to go with much more efficiency than if left to themselves. Well, in fact even our own body’s biochemistry has the ability to make such molecules that can take these minerals to where they need to go. Introducing the fascinating phenomena of minerals, chelation, and bioavailability.

What are minerals?

Minerals are naturally occurring chemicals that cluster together to form compounds, typically comprising of an element on the periodic table bound to something. That “something” can be either an organic or inorganic molecule. Minerals have a multitude of different chemical and physical properties¹ and can be categorized into thousands of different species. Minerals are also solid in nature, with the exception of mercury, at room temperature and ambient pressure. Some of the most abundant minerals found on earth (including in our bodies) are iron, magnesium, calcium, aluminum, silicon, sodium, and potassium, just to name a few. Think of minerals as clusters of a single atom (usually multivalent cations) that exists as a solid chunk. Once dissolved or freed from the solid it’s stuck to, the single positively charged atom is now naked and carries a charge. Because the atom wants to obey the octet rule, these naked atoms usually don’t last very long being single – they immediately look for a mate to partner up with. When partnered up, this attraction is typically in the form of an ionic bond. This type of bond is very strong due to each partner staying extremely close to one another because they’re both fighting over an electron. Putting chemistry aside, this plays a role in bioavailability and chelation, as we shall see.

What does bioavailability mean?

Bioavailability is actually defined as the proportion of a drug or other substance that enters the circulation when introduced into the body and so is able to have an active effect. That being said, it turns out that all chemicals that enter our mouths have a statistical probability of getting to where they need to go (or where we desire them to go) once they are swallowed. The likelihood of a given substance getting to its physiological destination depends widely on a myriad of biological variants. So, with that in mind, what is the likelihood of a mineral getting to its target tissue? Good question.

What is chelation?

So, when a positively charged atom (i.e. mineral) partners up with a non-metallic molecule, a special type of bond is formed called a chelate. This becomes very important in the bioavailability of minerals. Now the question becomes, what are the best chemicals to chelate minerals with? Minerals are usually chelated to inorganic or organic compounds. Inorganic compounds typically are oxides, phosphates, sulfates, etc. Organic compounds are pretty much every other compound found in nature that contains carbon. It turns out that a mineral actually has a better chance of getting to its target tissue when it is chelated to an organic compound rather than an inorganic one^2,3. The problem lies when the mineral enters the duodenum from the stomach. Naked minerals do just fine in their soluble state when floating around in the stomach due to the low pH of the gastric juices. However, once the pH increases, as in the proximal and distal sections of the duodenum, these unbound, or loosely bound minerals cluster together and precipitate. When this happens, they end up passing right along through the intestinal tract in which little to nothing actually makes it into the bloodstream. This is where a good chaperone comes into play. As stated earlier, intestinal uptake seems to be favored when the chaperone is an organic molecule (especially amino acids or intermediates of the citric acid cycle) as opposed to an inorganic molecule^4,5. Inorganic molecules tend to drop off the mineral at the wrong spots along the intestinal tract and force the mineral to compete for absorption with other minerals, including themselves, at that absorption site⁶. Think of it as if you were dropped off at the wrong bus stop and still had to fight the crowd to get on the bus. Organic chaperones such as amino acids and Krebs Cycle intermediates have a way of carrying the mineral through the intestinal wall and into the bloodstream intact, only to then to release them to their assigned serum transport vesicles to be taken to their final destination⁷. Total serum mineral distributions typically range from a small portion still being bound to their organic chelate chaperone, a larger portion being bound to serum proteins, and a nominal amount as in its free ionic state⁸.

New science & technology

Science has recently discovered that plants and animals actually make these chaperones that escort the mineral to its respective absorption site. For example, glycine is an amino acid, that when in its conjugate base form (glycinate) can carry a negative charge on its carboxylate group and latch right on nicely to a cation’s positive charge. The reason why the term “bis”glycinate is often seen on the back of supplement labels, for example, is because it requires 2 molecules of glycinate to quench the positive charge of mineral. Another class of chaperones that do quite an amazing job at transporting minerals are the intermediate molecules of the Krebs Cycle (aka. Citric Acid or Tricarboxylic Acid Cycle). When a molecule of pyruvate enters the mitochondrial matrix and links up with a molecule of oxaloacetate to form citrate, an amazing series of stepwise reactions take place to rearrange citrate to make all sorts of fun intermediates as well as different energy-storing molecules. These Krebs Cycle intermediates have unique physiological features and functions outside of just being the result of citrate rearrangement. The stepwise bond breaking and bond forming of citrate yields: aconitate → isocitrate → alpha ketoglutarate → succinyl CoA → succinate → fumarate → malate → oxaloacetate. These are what are known as the Krebs Cycle intermediates. Citric acid, for example, is one of the intermediates to the Krebs Cycle and is the main culprit for the sour taste experienced when a citrus fruit is bitten into. Citrate has the ability to grab on to (or chelate) various minerals and transport them to where they need to go within our bodies. Citrate also plays a role in hydroxyapatite formation⁹, a vital component of human bone. Another interesting little chaperone is Malate (in this case, malic acid). Malic acid is the sour-tasting compound found in most fruits and is used as a food additive. Besides playing a vital role in putting more pyruvate back into the Krebs Cycle to produce more oxaloacetate, malate has been shown to have other benefits. Due to its ability to reduce inflammation and platelet aggregation, malate has been suggested to have pretty amazing cardioprotective effects¹⁰. Not to mention its role in β-oxidation of fatty acids (fat burning). This cannot happen without malate’s involvement in the Krebs Cycle. So, it turns out that this little molecule can do more than just take minerals to their respective “bus stops”.

Conclusion

Taking all of this into consideration, one might look upon the human body with both wonder and irritation. Wonder as to the complexity and intricate design, and irritation as to why a nutrient can’t just get to where it needs to go once swallowed. Thankfully, we have science and technology to help alleviate us from this irritation. It is a wonder, however, to understand all of the different mechanisms and routes that are involved in nutrient transport and delivery, and then to use science to our advantage – namely via the use of biomolecules. With the discovery and invention of chelation for the purpose of mineral bioavailability, a lot of the irritation and guesswork thankfully is quickly coming to an end due to the help of our new-found friends, the molecular chaperones.

References

1. IMA Database of Mineral Properties/ RRUFF Project. Department of Geosciences, University of Arizona. Retrieved 2 November 2018.

2. H. DeWayne Ashmead, Comparative Intestinal Absorption and Subsequent Metabolism of Metal Amino Acid Chelates and Inorganic Metal Salts. Biological Trace Element Research. Chapter 24, pp 306–319.

3. Yenice E, Mızrak C, Gültekin M, Atik Z, Tunca M., Effects of Organic and Inorganic Forms of Manganese, Zinc, Copper, and Chromium on Bioavailability of These Minerals and Calcium in Late-Phase Laying Hens. Biol Trace Elem Res. 2015 Oct;167(2):300-7.

4. Vieira SL, Chelated Minerals for Poultry. Rev. Bras. Cienc. Avic. vol.10 no.2 Campinas Apr./June 2008.

5. Wilhelm Jahnen-Dechent, Markus Ketteler, Magnesium Basics. Clin Kidney J. 2012 Feb; 5(Suppl 1): i3–i14.

6. Cabell CA, Earle IP. Additive effect of calcium and phosphorus on utilization of dietary zinc. Journal of Animal Science. 1965; 24:800-806.

7. Ashmead HD. Comparative intestinal absorption and subsequent metabolism of metal aminoacid quelates and inorganic metal salts. In: Ashmead HD, editor. The roles of aminoacid quelates in animal nutrition. Westood: Noyes Publications; 1993.

8. Walker HK, Hall WD, Hurst JW, Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990, chp 143.

9. Hu, Y.-Y.; Rawal, A.; Schmidt-Rohr, K. (December 2010). Strongly bound citrate stabilizes the apatite nanocrystals in bone. Proceedings of the National Academy of Sciences. 107 (52): 22425–22429.

10. Xilan Tang et al., The Cardioprotective Effects of Citric Acid and L-Malic Acid on Myocardial Ischemia/Reperfusion Injury. Evid Based Complement Alternat Med. 2013; 2013: 820695.

Originally published on HNN