“You are what you eat” is an old expression your grandmother’s grandmother probably used, but it’s not actually correct technically speaking. Putting on my nerd hat to be a stickler for the details, it’s more accurate to say “you are what you absorb.” Grandma’s sage advice does a good job of illustrating that what we ingest is obviously essential to our health, but what we ingest that actually gets absorbed and utilized by the body is the crux of the issue truth be told.
The piles of studies that have been growing in recent years showing all manner of potential benefits of various nutrients has been very encouraging. We are experiencing an exciting time in nutritional science where new compounds are being discovered – and tested for their potential benefits – almost daily. Compounds that may help prevent cancer, improve immunity, improve weight loss, improve brain function, or improve athletic performance, to name just the tip of the iceberg of where science is currently looking to isolate and test various nutrients for their bio active properties.
How the process works:
Once a compound is discovered, it tends to get isolated, and then tested in either animal models and or in vitro (test tube) to test what positive or negative properties may exist as well as elucidate how they work. That is, understand not just what system they may impact (such as increase an animal’s ability to resist cancer causing chemicals for example) but also examine the isolated compounds’ “mechanism of action” which shows how it achieves the effect. How does that work? Let’s say some spice has been used for generations to reduce infections or improve immunity. Scientists might then feed, or inject, large amounts to lab animals (e.g., mice, rats, rabbits, etc.) and see if it does indeed have activity; perhaps testing how that spice reduces the size of tumors when the mice are exposed to known carcinogens, or bacteria known to cause infections and so forth. If that spice shows biological activity, scientists will often look deeper into that spice to see which specific constituent(s) in the spice are having the “active” compounds, and once found, will concentrate and isolate that active compound and further tests on animals, or humans, or in vitro (test tube) will continue. Foods and spices for example, are highly complex and can have hundreds or even thousands of biologically active compounds in them.
A few examples:
Green tea is a good example. Studies found green tea associated with a reduced risk of a number of diseases – such as various cancers – in populations who regularly consumed green tea. Green tea extracts were developed and tested, and scientists began to test the actual individual compounds found in the green tea extracts. Green tea was found to contain compounds known as polyphenols classified as catechins. Green tea contains six primary catechins: catechin, epicatechin, gallaogatechin, epigallocatechin, epicatechin gallate, and apigallocatechin gallate (EGCG). EGCG appears to be the most biologically active and is the most studied catechin found in green tea to date. Green tea also contains alkaloids including caffeine, theobromine, and theophylline. Many will recognize those last three as they are responsible for the stimulant effects of green tea and often found in various pre workout and energy type formulas. Finally, L-theanine is found in green tea and has been studied for its calming effects on the nervous system and often sold alone as a stress reducing supplement. BTW, It’s not unusual that a plant, or herb or food may contain compounds that have seemingly opposite effects to each other (such as caffeine and L-theanine found in green tea), but that’s another topic for another article.
A similar story exists for popular extracts such as grape skin extracts and Curcumin. Population based studies found reduced rates of certain diseases in people who consumed them, extracts developed and tested, and individual compounds within those extracts isolated . For example, Resveratrol is a compound found in grapes, red wine, and purple grape juice, and shown to have a wide range of potential health benefits, which include anti-inflammatory, cardioprotective, anti-oxidant, and anti-tumor activities, and is marketed and sold as a supplement. Resveratrol has garnered a great deal of interest with researchers as it continues to show a wide range of potential benefits, some quite unexpected.
Curcumin is found in turmeric spice and is getting a great deal of attention in the scientific and medical community, and rightly so. Curcumin contains a number of bio active compounds collectively called curcuminoids. Studies have been very promising and suggest curcumin may positively impact a wide range of human conditions, acting as an anti-inflammatory, antioxidant, chemopreventive (cancer-preventive) agent, and antineoplastic (cancer-fighting) , to name a few possible benefits of curcumin and it’s bio active constituents. As one would expect, curcumin is quickly becoming a popular nutritional supplement.
As this article is not intended as an extensive look into the science of these extracts per se, but an example of how discoveries are made and the growing list of studies that show real promise in preventing and or treating various human ailments using extracts and constituents found within them, bringing me to the reason for this article…
2+2 does not always = 4
The above would lead the reader to conclude the study findings must mean using these various extracts will help fight diseases or prevent them in humans. Well, per usual, it’s not that simple. If my decades of research in the nutritional sciences have taught me anything, it’s that 2+2 rarely = 4 in human physiology. Some times it equals 6, and some times it equals zero, but rarely as you expect. Such is the case for many of these extracts, hence the title of this article! As explained above, the typical process is to look at these extracts and or bioactive compounds isolated from those extracts in isolation, doing in vitro (test tube) studies and or feeding them (or injecting them) at very high doses to animals. Those studies are often extrapolated to humans. However, it’s often the case that when tested directly in humans, the results are less than impressive. Why? The answer to that gets complex quickly and depends very much on the individual compound being examined and studied, but some useful generalities can be discussed. Although each compound, be it extract, food, vitamin, etc. may have it’s own unique properties as to why human studies don’t live up to the effects found in animals or test tubes, two key issues are often at play as to why the human studies are disappointing when studies in test tubes and animals looks so promising, which can be summed up as “absorption and metabolism”
Absorption and Metabolism
Resveratrol is an excellent example of the second issue listed: metabolism. Resveratrol, in particular as trans- Resveratrol, appears to be adequately absorbed by humans. However, due to its rapid metabolism and elimination - and other factors – it’s actually considered to have a relatively low bioavailability and research is ongoing to find ways of improving Resveratrol’s effects in humans by employing novel delivery systems that may extend it’s metabolism. It’s important to note that the term “metabolism” as it applies to the topic covered here, is a highly generalized term for an extremely complex system beyond the scope of this article.
Curcumin is the poster child for the first issue mentioned: absorption. For any compound, vitamin, or nutrient, it must get digested and absorbed to be metabolized. Many people are under the impression digestion and absorption are a simple matter of everything we eat being dumped into some acid in the stomach, and absorbed. Nothing could be further from the truth and human digestion is an extremely complex system. For brevities sake, I’m going to cover the essential basics, using curcumin as an example. It’s well established that compounds with poor solubility are poorly absorbed and have poor bioavailability. Compounds must be “solubilized” by the body before they can be absorbed. It’s accurate to say that solubilization, absorption, and metabolism are three key steps that modulate oral bioavailability of an ingested compound. In many cases, there’s a direct relationship to the solubility of the compounds or nutrient and it’s bioavailability. Most people have heard of fat soluble and water soluble vitamins for example, and have a better understanding of the basic concept of solubility than they may think.
If you dump a T-spoon of table sugar into a big glass of water and stir, it mixes fairly quickly. It’s solubilized. If you dump a T spoon of vegetable oil into the glass, no amount of stirring will get them to mix together, because oil (lipids) are not water soluble. If you dump a T spoon of sand into water or oil, no amount of stirring will get it to mix into either, as an extreme example. What if something has very poor water and fat solubility? Well, it tends to go right through you just as the sand would! That’s a highly simplified overview of a very complicated process, but it’s “good enough for government work” as they say to explain the essential concept of solubility.
From the above discussion then, it should come as no surprise that improving the solubility of a compound with poor solubility will often dramatically improve its absorption and bioavailability. In fact, the rate at which poorly water soluble compound dissolves is often the slowest step and therefore can be what’s referred to as the “rate-limiting” step in bioavailability of the compound. Needless to say, for compounds with poor solubility, a key step to improving their bioavailability and effect, is to improve its solubility. There’s a number of technologies companies can employ, some times as simple as micronizing it (reducing it to very small particle sizes) to complex and proprietary processes unique to a company.
Using curcumin as the example, In one study, people were fed up to 12,000mg (12g) of curcumin extract, and virtually no detectable curcuminoids were found in their blood. Curcumin is considered to have extremely poor solubility and various technologies have been attempted to improve it. One potential benefit of improving solubility that benefits buyers and sellers is, improving solubility may allow lower doses to be used to derive benefits, saving space and money for all involved.
One interesting technology recently developed by Glanbia Nutritionals called PhytoForce™ shows real promise when applied to compounds with poor solubility like Curcumin. The PhytoForce™ technology applied to Curcumin showed a 350% increase in solubility and an even more impressive increase in permeability, which are substantial improvements that should result in greatly enhanced bioavailability. Additional botanically derived extracts the technology has been applied to are Milk Thistle, Chrysin, Green tea extract, resveratrol, quercetin and as well as others.
Readers should note this technology is not sold retail, but directly to companies looking to apply it to their products or formulas. For additional information on the PhytoForce™ technology, the company can be contacted directly at: firstname.lastname@example.org
Discovery of various compounds derived from herbs and other botanicals is an exciting area of nutritional research. Some are proving to be of value in both disease prevention and treatment in humans, vs. say just rats and mice! However, as outlined in this article, discovery and isolation of the active components is only part of the process in terms of being of any real benefit to human beings ingesting them in supplemental form. They need to actually be absorbed and utilized to be of any real value. The application of specific technologies to greatly enhance absorption – especially as it applies to compounds with poor solubility – is an area of research starting to yield novel and useful technology that will improve bio availability.
PhytoForce™, is product of Glanbia plc.
Companies interested in the applying this technology to their products should contact: email@example.com
Bioavailability of resveratrol. Ann N Y Acad Sci. 2011 Jan;1215:9-15.
Resveratrol in medicinal chemistry: a critical review of its pharmacokinetics, drug-delivery, and membrane interactions. Curr Med Chem. 2012;19(11):1663-81.
New delivery systems to improve the bioavailability of resveratrol. Expert Opin Drug Deliv. 2011 Aug;8(8):973-90
Administration of resveratrol: What formulation solutions to bioavailability limitations? J Control Release. 2012 Mar 10;158(2):182-93.
Conundrum and therapeutic potential of curcumin in drug delivery. Crit Rev Ther Drug Carrier Syst. 2010;27(4):279-312.
Bioavailability of curcumin: problems and promises. Mol Pharm. 2007 Nov-Dec;4(6):807-18. Epub 2007 Nov 14.
Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003 Jan-Feb;23(1A):363-98.
Investigation of the absorption mechanism of solubilized curcumin using Caco-2 cell monolayers.J Agric Food Chem. 2011 Sep 14;59(17):9120-6. doi: 10.1021/jf201451m. Epub 2011 Aug 17.
Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006 Mar 17;6:10.
Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. Eur J Pharm Biopharm. 2011 Feb;77(2):275-82. doi: 10.1016/j.ejpb.2010.12.006. Epub 2010 Dec 13.
Solubility enhancement of lovastatin by modified locust bean gum using solid dispersion techniques. AAPS PharmSciTech. 2008;9(4):1262-9.