Size Does Matter Part III

Updated: Jun 8, 2021

We’ve seen how molecular form and size of ingredients in a nutraceutical or nutritional formula play out in the marketing of protein supplements.

Original post: March 21, 2011




Whey protein products, for instance are often compared and marketed as ‘denatured versus the undenatured peptides’. Research demonstrates that certain peptides in whey have biological activity way beyond the basic building blocks they deliver. However, if denatured (broken down) by processing, this biological activity, such as appetite suppression through cholecystokinin elevation, is not experienced.


Glutathione elevation by whey proteins is a central way these proteins actually preserve and allow for the building of muscle. It’s rarely discussed in the bodybuilding forums from this perspective because builders often want to hear about biological value and anticatabolic activities which are, in fact, important features of the precious whey protein.


In fact, the dipeptide glutamyl cysteine, is a precursor for glutathione and can elevate intracellular glutathione much faster than even glutathione supplements can. However, if the whey protein is hydrolyzed to the degree that these peptides have been denatured, the rate in which these glutathione building blocks make it into the cells for glutathione reconstruction, declines. Hydrolyzation (predigesting), a regular practice, changes molecular form and size of the active peptides.


Glutathione is a critical element that contributes to the anticatabolic and anabolic drive of whey protein. It also contributes to the reduced soreness and faster recovery rate attributed to the regular use of properlyprocessed whey protein supplementation. More discussion on whey protein and these features is available in a subsequent article

WHEY Performance beyond just building muscle!


This subject of ‘denaturation versus undenatured peptides’ also comes into play with regards to biological value of protein where we know di- and tri-peptides, for example, to deliver bigger payloads of amino acid building blocks into the circulation for tissue recovery and anabolism; better than hydrolyzed products typically can.


In this case the smaller components, the free amino acids, don’t deliver the same building block payloads (and subsequently biological value) in the blood stream as the undenatured di- and tripeptides. A high oligopeptide (long chains) portion versus the di-and tripeptide component changes the biological value of the whey. Size and molecular specs matter.


This whey peptide absorption is an interesting subject matter that is often not well understood by consumers. Unfortunately a denatured product just doesn’t deliver the same benefits.


It works like this.


The mucosal cells lining the gastrointestinal tract (small intestine) can absorb the amino acids from a hydrolyzed protein source one by one and then shuttles them into the blood stream one by one. This slow process is much like choosing to pick up the pennies in a pile of change you’ve just stumbled upon instead of picking up the quarters.


The case of the undenatured protein product that still has an abundant supply of intact di- and tri-peptides, these same mucosal cells can absorb dipeptides (two amino acids) and tripeptides (three amino acids) at a time, and process (intracellular digestion) these peptides within the mucosal cell releasing as many as three amino acids at a time in the blood stream as opposed to one at a time. This results in a faster more complete amino acid profile in the blood stream immediately for lean tissue recovery and anabolism – no amino acid limitations.


So if you’re falling prey to the predatory rants about hydrolyzed wheys being higher in biological value than those that are not hydrolyzed, ouch. In this case smaller molecular size doesn’t work better. Do your homework and select the undenatured whey. Whey is not whey. Just like casein is not casein. Hydrolyzed casein simply cannot deliver the same bioactivity as undenaturedforms.


In fact, casein, the undenatured form, delivers many biological effects that we take for granted in whole milk such as angiotensin regulation through specific peptide sequences and configurations of the casein fraction. Some of these fractions also deliver an opiate-like pain relieving activity – probably why some can become addicted to dairy products like cheese so easily (in addition to the tyrosine contents). But the common caseinates we see in protein powders don’t have the same activity because they’re denatured.


Retention of the tertiary 3-dimensional configuration of the protein allows for the activity to stay intact. This includes an influence on insulin which some research is demonstrating to be significant. Although this influence is said to be the insulogenic factor that may be contributing to the epidemic levels of insulin resistance and diabetes, if harnessed correctly, it actually pumps up insulin to improve anabolic drive according to our preliminary work at BNHR; an example of the former FREAKn lab geek, thinking in line with that of your FREAKn goal.


In fact, as the latest in nutrigenomic science peels away the biological layers to our genetic codes and how they interact with specific whole nutrients or specific isolates from nutrition, we are gaining a better appreciation for how they can be used as natural aids in health, performance and also those massive extreme goals.


Molecular weight of chondroitin, for example, plays a huge role in its pharmacology against joint rehabilitation or wear prevention. High molecular weight forms (larger molecules), in this case, cannot penetrate to deliver the beneficial regenerative effect. If you think this molecule isn’t of any value to you during your muscle mass initiative, think again. Maintaining connective tissue throughout in the body is critical to overall tissue integrity.


Muscle, bone, skin and pretty much every tissue in the body depend on underlying connective tissue integrity to stay intact and be built in to that stronger freakish size you might be striving for. The right chondroitin literally turns ON the cells responsible for manufacturing collagen. The wrong one simply does not. Hence the conflicting data on this collagen subject in the research. But this example of conflicting results in the laboratory and in practice by you exists with creatine, nitric oxide nutrition, insulin optimization and more.


Which leads me to the point of the article – integrity; if you are not able to discern the myriad of research documents on the ingredients needed and their molecular forms that are, in fact biologically appropriate, to maximize insulin efficiency, gH, testosterone, anabolic drive and lean mean freakish muscle, because you just can’t be bothered, or you don’t have the time or scientific background, leave it to those who are supposed to do the legwork on your behalf.


The manufacturer of your supplements should be held accountable for this work. Choose a reputable firm that delivers to market with integrity and with a mindset that understands your needs. A respect that sets the foundation for an understanding of how important it is to get the most from your hard work in the gym; not to waste your money and time; a company made up of ‘been there’, ‘done that’ and are still doing it just like you are – FREAKn Muscle (new cutting-edge hardcore bodybuilding brand formulated prepared by Franco Cavaleri).


read more in books

Read part I

Read part II

Go directly to Drug-Nutraceutical Interactions database

read WHEY Performance beyond just building muscle!

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