Ask Dr. Andro: Does the Deer Velvet Antler Spray NFL Fullback Heath Evans is Supposed to Have (Ab-)Used Work? Does it Contain IGF-1 & Can IGF-1 Be Taken Orally?

Question from Lerner: "Dr. Andro, check out the following link. It's about deer antler (which I didn't find being discussed in a search of suppversity) -- and how that supposedly contains IGF-1. I don't watch NFL football, but they do get paid big money and that motivates them to try different things for sure. Still, does it work, or is it just placebo effect?"

Image 1: Legal growth hormone
supplements in the NFL? How legit is
the deer velvet antler extract containing
'The Ultimate Spray'  (image source
official SWATS homepage)
Answer from Dr. Andro: Initially, I wanted to dismiss this one all together, because I remembered out of my head one of two peer-reviewed studies on the use of deer antler, which was not able to find any effect of elk velvet antler extract at a daily dose 560mg on exercise performance or endocrine parameters in 25 male and female rowers (Syrotuik. 2005). How on earth would the hilariously labeled The Ultimate Spray, Heath Evans is supposed to have taken, then make a difference for a high level NFL fullback?

Well, after "pubmeding" (make sure you remember this neologism of mine, it is like "googling" for smart people ;-) the missing study by Sleivert et al. (Sleivert. 2003), in which at least some of the 38 active males, who had received deer antler velvet extract in powder form concomitantly to a 10-week strength training protocol, actually gained twice as much isokinetic knee-extensor strength and endurance than the placebo group, Mr. Lerner's question suddenly had my full attention...

What is The Ultimate Spray?

A closer look at The Ultimate Spray then revealed that, other than I had expected, it was no Patrick Arnold style transdermal, but an oral preparation. Well, to be precise this is only my interpretation of the information, if you would like to call it such, on the website, of the producer SWATS, where it says, I quote:
"sparyed into the moutn, where the phospholipid spheres easily penetrate the mucosal layers of the moutn and go directly into the blood stream." [my emphasis]
So if to "spary" something "into the moutn" means to spray it into your mouth and not to smear it onto the next best mountain, I would assume that the undisclosed amount of "liposomal encapsulated" (sounds funky, no?) velvet antler extract, one serving contains, is supposed to be taken up orally - in that, I exclude sublingual delivery because a) it says that you got to spray it "into" your "moutn" and not under the tongue and b) the liposomal encapsulation would make little sense if the IGF-1, which is supposed to be in the product, would not even reach the digestive juices and enzymes of the stomach, from which the encapsulation in turn is supposed to protect it. Note: The amilase and lipase in the saliva would not harm the protein based IGF-1 peptides, anyway.

How is the product supposed to work?

Now that we know that The Ultimate Spray is a liposomally encapsulated extract from deer antler velvet that is to be taken orally as a spray, the next question we would have to answer is: How on earth does this product make Evans feel improvements in "some rest and recovery aspects" and what is the "sleep of a deeper nature" the New Orleans Saints fullback mentions all about?

A look at the purported ingredients of the product could help, but as a matter of fact, without appropriate lab analysis, we have no clue how much, if any, IGF-1, collagen, amino acids, epidermal growth factor (EGF), chondroitin sulphate, erythropoietin, glycosphingolipids, prostoglandins, phospholipids and monoamine-oxidase inhibitors The Ultimate Spray ultimately contains. What we can say for sure, however, is that IGF-1 is not "a precursor for the production of growth hormone (HGH)", as SWATS tries to tell you. It is rather a hormone whose molecular structure is very similar to insulin and which plays an important role in childhood and - you guessed it - deer antler growth.

If we leave the "amino acids", "collagen","phospholipids" and "monoamine-oxidase inhibitors" aside (you could get these in much higher concentrations from food or way cheaper supplements, anyway) IGF-1, EGF, the unspecified prostaglandines and last, but not least, every cyclist's favorite blood building 'supplement', erythropoietin, are the most likely candidates on the ingredient list which could be responsible for the beneficial effects Evans claims to have noticed. So let's see...
  • Erythropoietin, commonly known as EPO, is in fact a naturally occurring glycoprotein hormone which does - as its name suggests - control erythropoiesis, or red blood cell production. The usual dosage that is used for doping purposes is 100IU/kg three times per week for the first 8 weeks, to increase red blood cell count, followed by 25-50IU/kg to maintain stable erythrocyte counts. According to Jelkmann, 1mg of pure synthetic EPO has a standardized efficiacy of 130.000 IU, while EPO from human urine has meager ~2IU/mg (Jelkmann. 2009). It stands out of question that there will be at least trace amounts of erythropoietin in the extract, since the antler of deer is supplied with blood, but even if it had an efficiacy of 50% of the purified rDNA-derived human EPO, a man like Evans who certainly weighs >160 pounds would have to get >3.500 IU or 18mg per day right into his blood stream to get the desired effects. This is something that probably is not going to happen, as the previously cited study by Sleivert et al. (Sleivert. 2003) shows that notwithstanding inconsistent beneficial effects on strength and endurance, the antler extract did not raise red cell mass or VO2max, parameters which should have been affected, if the amount of EPO in the supplement would have been adequate to elicit physiological effects.
  • Prostaglandins are, in contrast to what SWATS claims not generally anti-inflammatory. The function of these locally acting messenger molecules are diverse and the blatant statement on their "anti-inflammatory" character, the producer makes here, is not worth the webspace it occupies. Whether or not Evans could have felt their effects would really depend on which kind of prostaglandins the product contains, but I bet that this is something even the SWATS team does not know.
  • Epidermal growth factor (EGF) does play a role in the regulation of cell growth. Thus it is no wonder that it can be found in a constantly regrowing tissue, like deer antler (Ko. 2004 & Barling. 2005). Yet, even if it was retained in the extract, I have my doubts that it plays a major role in the ergogenic effects Evans has been talking about.
This leaves us with what the original Yahoo article on the subject also dealt with: IGF-1, a basic peptide hormone composed of 70 amino acids, which - and this has been shown by Gu et al. - is "only detectable in osteoblasts around the bone in the mid and base parts" (Gu. 2007) of deer antler. So, if the extract SWATS uses in their The Ultimate Spray was made from whole deer antler, it will in fact have IGF-1 in it. Whether this would be enough to elicit physiological effects cannot be decided without running an ELISA or HPLC test on the product to find out how much IGF-1 actually is in one serving of The Ultimate Spray (cf. Liu. 2011). But wait... being a large peptide, would the IGF-1 be able to be absorbed into circulation, even if - as the producer promises - it is protected from digestive enzymes by liposomal micro-encapsulation?

Image 1: Parts of the small intestine,
relevant for IGF-1 absorption in the
rat model used by Kimura et al.
Can IGF-1 be taken orally?

The surprising answer is: "Yes, it can." After digging through the archives of various pharmacological journals I eventually came up with a 14-year-old study by Kimura et al. (Kimura. 1997), who, in 1997, investigated the bioavailability of orally administered recombinant human insulin-like growth factor I (rhIGF-1) [the attribute "recombinant" indicates that this is synthetic human IGF-1] in adult rats (I deliberately underlined the "adult", here because in various neonatal or new-born / very young mammals the intestinal permeability is elevated to allow for the absorption of larger peptides from the mother's milk). The results of this study (cf. figure 1), I must admit, did really surprise me. If you add up (note: if you think I miscalculated, you probably just added up the percentages from figure 1 and forgot that when you absorb 35% there is obviously less IGF-1 left, of which, in a second step. another 17% will be absorbed, etc.) the amounts of IGF-1 that reached circulation (i.e. became "bioavailable") via the three different parts of the digestive tracts of the rats, the critters ended up with roughly 50% of the orally administered radio-labeled 125I-rhIGF1 actually getting into their blood stream:
Figure 1: Bioavailability of orally administered rhIGF-1 with and without peptidase inhibitors.
(data adapted from Kimura. 1997)
As you can see, even without the addition of a peptidase inhibitor (peptidase = protease; enzyme that breaks down peptides its individual constituents and would thus "degrade" the IGF-1 before it could even be absorbed) the orally administered dose of 1.0mg/kg (human equivalent: 0.16mg/kg or 13mg for an 80kg adult human being) was absorbed at rates of ~35%, 17% and ~6% in the jejunum (middle section of the small intestine), the ileum (final section of the small intestine) and the large intestine, respectively.

This is not yet the "95% absorption" SWATS promises for a product they advertise as being "by far the best supplement for sports performance", but it is still adds up to a respectable amount of IGF-1 actually reaching circulation. To be precise, plasma concentrations peaked roughly 3 hours after administration at ~50ng/ml, ~180ng/ml and 375ng/ml for the no peptidase, the aprotinin and the casein groups, respectively. In both, the no peptidase and the casein groups, levels stayed constant for another 3h, after which they declined linearly.

I don't know about you, but when I hear about casein improving the absorption of IGF-1, I suddenly forget about dubious deer antler sprays and start thinking of colostrum - well, but I guess this would be a topic for another week ;-)

So what, Dr. Andro? Does it work?

As much as I would like to provide you with a definite answer, the only thing I can tell you for sure are the following facts:
  1. there is IGF-1 in whole deer antler
  2. IGF-1 survives passage through the intestines of rats even if it is not micro-encapsulated
  3. non-micro-encapsulated IGF-1 can be taken up in the jejunum, the ileum and the large intestine at surprisingly high rates
  4. protease inhibitors, above all, the readily available and reasonably priced peptidase inhibitor casein can improve bioavailability even further
I would yet have to speculate on
  1. whether or not the deer velvet antler extract used in The Ultimate Spray was derived from parts of the antler that actually contain more than trace amounts of IGF-1,
  2. how much IGF-1 actually is in one serving,
  3. how effective the "natural" and probably partly bound (to IGF1 binding globulins) form of IGF-1 in the product is compared to synthetic, free rhIGF-1,
  4. if the liposomal encapsulation does in fact improve and not maybe even hinder absorption,
  5. and, last but not least, if the amount of IGF-1 reaching the bloodstream would aactually be able to produce physiological effects
in order to answer Lerner's question. So, now that you got the facts, its up to you, students of the SuppVersity, to make up your mind on whether or not there is more behind this lurid yahoo news-story than just a clever marketing stunt.
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