Prototype Nutrition Ketoforce

Aug

2

Instant Ketosis?

By Patrick Arnold

 

In late 2010 a professor from a university in Florida approached me to see if I could synthesize a compound that he wanted to use in his research.  This compound was what is known as a “ketone ester”.  This ketone ester is a synthetic prodrug which, after ingestion, your body naturally breaks down into the ketone bodies beta-hydroxybutyrate (BHB) and acetoacetate (AcAc).

Ketone bodies are energy sources that your body naturally produce and burn under special metabolic conditions.  These conditions include starvation and a very high fat / low carbohydrate diet (known as the ketogenic diet).   Ketones are the end products of fatty acid metabolism, and compared to your body’s major source of caloric energy (glucose), they are pretty amazing.  Unlike glucose, ketones do not require insulin to enter cells and be incorporated into the metabolic cycles that generate the cellular fuel ATP.  They cannot be converted to body fat. Also, unlike most fats, ketones can freely enter the brain where they are an excellent fuel for brain cells.  On top of all that, ketones generate more ATP per unit oxygen consumed than any other energy source.  Ketones are essentially your body’s super fuel.

I ended up successfully synthesizing this ketone ester for the professor, and he ended up performing some pretty cool studies utilizing the product.  For instance in one study he made rats resistant to the toxic effects of high pressure oxygen upon the central nervous system (this has major implications for deep sea divers such as navy seals, as well as indirectly on folks suffering from epilepsy).  In another study he almost completely halted the growth of cancerous tumors in rats by giving them the ketone ester.  The professor also showed in a more informal study that rats taking the ketone ester could exercise quite a bit longer than control rats.

As a supplement manufacturer I found the potential health and performance implications for raising ketones through the administration of a “ketone supplement” very exciting.  Unfortunately the ketone ester I made for the professor is both  synthetic and extremely expensive, so it was wholly unsuitable for sale as a supplement.  My collaboration with the professor did get me thinking though, and I set out to see if I could develop a way to raise ketone levels by administering a natural product alternative.

My focus was on the ketones themselves.  As I mentioned previously, there are two major endogenous ketones: beta-hydroxybutyrate (BHB) and acetoacetate (AcAc).  AcAc I had to eliminate right off the bat because it is too unstable (it breaks down relatively quickly to acetone and carbon dioxide).  BHB on the other hand was a possibility – particularly in the form of one or more of its salts.  The problem was the only BHB salt which is commercially available is sodium BHB and it’s just too expensive.  So I had to embark on my own R&D project to figure out how to make BHB salts at a price that is not completely out of reach.

I ended up perfecting a proprietary manufacturing method for sodium and potassium mixed BHB salts.  Why mixed sodium and potassium salts?  The reason for that is because at the level of intake of BHB required for benefits you would have to ingest a substantial amount of cation (positively charged mineral such as sodium or potassium).  At such levels of cation ingestion it made sense that a balance of sodium and potassium salts would be the healthiest thing to do.

Additionally, I discovered that the product had to be delivered as a concentrated liquid because potassium BHB is simply too hygroscopic to isolate as a powder (it picks up water from the atmosphere and turns into mush at an astonishing rate, whether by itself or mixed with sodium BHB).

So, just to make things clear, is I have developed a supplement product that raises blood ketone levels.  This product does not require a ketogenic diet to raise ketone levels as it is essentially providing an external source of ketones.  As such, it will raise ketones even if you eat a plate of spaghetti before taking it (still, its benefits are maximized when combined with either a ketogenic or other sort of low carb diet).

This kind of thing is a lot of work.  For instance it involved developing novel analytical testing methodologies (which as an organic synthesis guy isn’t second nature by any means!)  But after about a year of work  this weekend I am proud to announce the introduction my sodium and potassium mixed  BHB salts on my prototypenutrition.com website.

https://www.prototypenutrition.com/ProductDetails.asp?ProductCode=KF

I hope to continue this topic next week and introduce you to some blood data and exercise performance data on my BHB salts that I think you will find very exciting.  Also I will give some tips on how to possibly best uitilize this product for whatever health or fitness goals you may have.

So stay tuned!

Jun

4

Progesterone Derivative Sold as Prohormone

By Patrick Arnold

 

I was recently asked a question about a very strange new prohormone product.  What makes it strange is that is actually based on a female hormone – specifically it is based upon a hormone called 17alpha-hydroxyprogesterone.

17a-hydroxyprogesterone (or 17-HP) is a hormone intermediate in the steroidogenic pathway between progesterone and androstenedione.  17-HP is present in the blood of women in varying amounts during their monthly cycle and is present in particularly high amounts during pregnancy.  It has similar actions to progesterone  (albeit somewhat weaker), and is thought to serve a complimentary role to progesterone as an endogenous progestogen.

The prohormone in question here is not actually 17-HP however, but a close structural derivative to 17-HP that I will call Dehydro 17-HP.  For all intents and purposes however, the metabolism of the derivative should be analogous to 17-HP.  Specifically, here are the potential pathways of the two

17-HP ——– Androstenedione  —– Testosterone

Dehydro 17-HP ——— Boldione ——–  Boldenone

 

So it is definite that the potential for 17-HP and Dehydro 17-HP to convert to active anabolic/androgenic hormones is there.  There are two questions though.  How much do they convert and is there any HPTA suppression from the progestational action of the parent compounds?

Perusing the research on 17-HP I did find a little bit of information on the first question.  Apparently at least one study found that given to humans and to rats the compound results in a substantial increase in urinary 17-ketosteroids (androgenic metabolites).  This indicates that it does convert to a significant extent to androstenedione at least.  Furthermore, a study where 17-HP was given orally to cockerels (immature roosters) showed it to have one half the androgenic activity of methyltestosterone.  It is important however to note that androgenic activity in a cockerel is measured by the size of that red comb on their heads, which is not necessarily easily translatable to anything in a human.

The answer to the second question –  involving whether the compound is HPTA suppressive – is harder to answer.  Data on women show varying effects on 17-HP at different times throughout the cycle, but this data is irrelevant to men.  I couldn’t find anything on men and LH/FSH levels.  So that part of the equation remains unanswered.

I guess I don’t really know what to say about this stuff.  If it works at all I would expect one to have to take many hundreds of milligrams before an effect is seen (due to it being a two step conversion via an intermediary dione).  Whatever the case, it is sort of amusing how creative companies will get in an attempt to fulfill customers’ demands while trying to minimize legal exposure.

Apr

9

More Craziness over Craze

By Patrick Arnold

As I said in my last piece, things are moving fast in this Craze scandal.  Word just came out today that the product was tested in Sweden and confirmed to contain the same meth analog that the Australian federal police said they identified

“In this material we found substances chemically similar to amphetamine and that probably would have similar effects to amphetamine has been says Anna Stenfeldt Henning, Head, Drug Analysis Unit, SKL.”

SKL is the Swedish National Lab for Forensic Science. The Swedes refer to the chemical as N-ethyl-1-phenyl-2-butylamine, but it also goes by the names N,alpha-diethylbenzeneethanamine and N,alpha-diethylphenethylamine.  As I mentioned in my last installment it is considered a structural isomer of methamphetamine.  Why is it considered a structural isomer to methamphetamine while some other phenethylamine derivatives are not?  If you want to get technical it is because it contains an alkyl (hydrocarbon chain) alpha to the nitrogen atom.  The presence of the alkyl group blocks the enzyme monoamine oxidase, which normally inactivates such neurotransmitter type compounds.  In other words it makes it potent so you get the classic “speed” high.

This testing by the Swedes comes on the heels of a consumer who took Craze for two weeks and ended up in the hospital.  This case led the magazine SVT Nyheter to contact the SKL who then took it upon themselves to test the product.

The makers of Craze have responded to SVY Nyheter by claiming that their product does not contain the meth analog and that it must be one of the counterfeit Craze jars that allegedly have been floating around europe.  However, SVT Nyheter contacted the retailer that they bought the Craze from and they claimed to have bought it directly from Driven Sports.

I have yet to hear of any action regarding this product here in the states.  Online retailers continue to sell the product.  I don’t know if that is going to continue for long.   The liability of selling a product with the knowledge that it may contain an illegal and potentially dangerous substance might be too risky for large distributors and retailers.  Usually in situations such as this the product is put on temporary hold until more information is available and the situation clarified, because not to do so puts a company at potentially greater legal risk in the future should the fears be confirmed and a criminal investigation launched.

So if you love your Craze, and you don’t care about any of the scary stuff coming to light lately, you might want to stock up.

www.svt.se/nyheter/regionalt/vastnytt/vanligt-kosttilskott-innehaller-dopningsmedel

Apr

4

Craziness over Craze

By Patrick Arnold

Driven Sports (formerly Designer Supplements) is a somewhat popular company in the sports nutrition arena. They have a dedicated cult following due to their history of introducing controversial and intriguing products such as the now infamous designer steroid “superdrol” to the market place. Their latest hit product is a “pre-workout” product called Craze. This product gained insane popularity over the last couple of years and users who have taken it have reported amazing energy and euphoria. Since the ingredients on the label did not seem to list anything that could explain such remarkable effects, much suspicion arose over whether the product might be “spiked” with some sort of undisclosed stimulant compound.

Well, in early February that suspicion reached a fever pitch when supplement retailers disclosed that federal police in Australia told them that Craze (which has been a popular import there) was found to contain a methamphetamine analog. It appears from various sources that the analog they were referring to was N-alpha-diethyl-benzeneethanamine.

As a consequence, Craze has been banned from Australia and all imports are now being confiscated. Curiously, this comes right on the heels of an announcement of the ban of a Rugby player by the Australian Sports Ant-Doping Authority (ASADA) for the same chemical analog plus another analog called 1-phenylbutan-2-amine (which interestingly would be an expected metabolite of the analog allegedly found in Craze). No mention however is made that this positive is the result of the athlete ingesting Craze.

I am following this story closely and right now there is nothing completely confirmed by any official documentation. One thing is curious though, and that is the fact that craze does contain a compound on the label with the exact same molecular formula – differing only by the placement of one of the ethyl groups.

Very curious. What could this mean? Could the aussies have mistaken this listed ingredient for the meth analog? Very doubtful, as they must have been fully aware of the difference. Also, from my research the actual mass spectrum for the analog appears to be recorded in the literature, and so could be matched up. Conspiracy theorists might imagine that a company who wanted to slip such an analog into a product could try to throw testers off by listing an extremely close structural isomer on their label. Hmmm…

Right now it is not clear what is going on but things are unraveling and I will keep everyone updated soon. As far as what the ramifications for Driven Sports would be in the United States should this all prove to be true….well…. that can vary from minor to major. Perhaps a warning from the FDA or worse a criminal charge of adulteration / misbranding etc. Worse still would be a felony charge of distribution of a controlled substances, since analogs of CII substances like methamphetamine can be considered also controlled under US law.

Stay tuned

 

 

mass spec

Feb

5

Stem cell breakthrough for muscle repair and growth??

By Patrick Arnold

What if they could liposuction fat out of you, put it in some machine, and then get super cells out the other end that you could have injected into your muscles to repair injury and possibly cause local growth? It sounds pretty cool doesn’t it? Apparently this is what some new research suggests is possible, and thanks to some recent technological breakthroughs it appears that it might not be too difficult or expensive to do.

You probably have heard of stem cells. Stem cells are a special kind of cell that exist in a sort of “unprogrammed” state. There are many different kinds of stem cells that can be derived from many different tissues, but the fundamental property they all have is a varying ability to differentiate from their primordial state into cell types of all sorts such as blood cells, heart muscle cells, bone cells, organ cells, brain cells etc.

The most useful stem cells are those derived from embryos and they are known as “pluripotent” stem cells. That basically means they have the ability to differentiate into any cell type in the body. Due to ethical concerns, and the obvious raw material limitations of harvesting embryos, this sort of stem cell does not enjoy practical exploitation in medicine. There are also stem cells that can be harvested from adult tissues. Although adult bodies primarily consist of fully differentiated cells that serve our various needs, there also are stem cells present. Adult stem cells are known as multipotent stem cells. They don’t quite have the flexibility to easily morph into anything like embryonic stem cells do, but they can be coaxed to differentiate into lots of useful cell types. And of course they don’t share the controversy and limitations associated with embryonic stem cells.

Blood marrow has been one such important source of multipotent adult stem cells for medical research and application in the recent past. As useful as bone marrow is however, the process of drilling into your bone to suck out the marrow is invasive and distasteful. Thankfully, in recent years it has become apparent that fat stores harbor an impressive variety of adult stem cells as well (reportedly containing 100-300 times as many useful cells as blood marrow).

Fat stores are easily accessible. Cosmetic surgeons suck out pounds of the stuff every day from women’s hips and men’s bellies and then proceed to chuck it all in the medical waste bin. Adipose tissue derived regenerative cells (ADRCs) as they are called can be isolated from all this waste fat, however until recently the process has been less than rapid and practical because it involves a prolonged culturing period. Luckily, a new filtering system has been developed which rapidly separates out the ADRC fragments of the fat and dumps out all the needless junk. [ADRCs by the way consist partly of adipose tissue derived stem cells as well as other progenitor cells of value to injury repair such as vascular related endothelial cells, fibroblasts, and preadipocytes.]

In recent years there have been some interesting studies performed using ADRCs in muscle tissue. In one study, the cells were injected into mice with muscular dystrophy and the muscle strength and resistance to fatigue improved http://www.ncbi.nlm.nih.gov/pubmed/21874281. In another, the cells were injected into normal mice and new muscle tissue was observed to be formed at the injection site http://www.ncbi.nlm.nih.gov/pubmed/16887099. Just recently though a study was released looking at the effect of ADRCs on muscle tissue injury in mice, and the mechanisms of the actions were examined in more detail then in the previous studies http://www.ncbi.nlm.nih.gov/pubmed/23239611.

In this study rats had their tibialis anterior muscles lacerated with a scalpel. One group had a simple phosophate saline solution injected at the site, a second group had human bone marrow stem cells injected, while a third were injected with human ADRCs. The rats injected with ADRCs showed greatest improvement in healing out of the three groups. The formation of new blood vessels (angiogenesis) and new muscle cells (myogenesis) was observed, and fibrosis was suppressed.

The researchers looked to see exactly what was going on. Since the rats were injected with human progenitor cells they could examine certain markers to see if these cells were differentiating into muscle and vascular cells in the rats. Although that was observed to a small degree, it appeared that what was mostly going on was that these injected cells were secreting lots of cytokines and growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and these were stimulating the rapid repair and regrowth of the native tissue in the injection area.

Whatever the mechanism, the technique seems to have potential due to its ease of preparation and also due to the low risk of immune rejection (since one’s own cells are being reinjected into their body). Also, we don’t know whether if when human ADRCs are injected into human tissues there may be more actual differentiation into new tissue going on, and not just mostly paracrine stimulation of growth of existing tissue from secreted growth factors.

I expect to see this technique to soon gain popularity in elite sports injury repair along with current new fangled techniques such PRP injections.

Jan

11

The Bulimia Machine

By Patrick Arnold

You may have heard of the new personal stomach pump invention by the guy that brought us the Segway personal transport thingy. The contraption is called the AspireAssist Device. In Europe the device has been clinically tested on several overweight people and found to be very effective over the long term. 24 obese people lost an average of 49 percent of excess weight (which comes to around 45 pounds) after using it as directed for a year. The makers of the AspireAssist device hope to gain FDA approval sometime in the near future.

This story has caused a lot of controversy. First of all, the product itself works in a rather disgusting manner. Basically it works like this – you get an operation where a tube is installed the goes from the inside of your stomach out through the front of your body. There is an opening on your belly skin where you can stick some sort of pump device. The idea is, after you eat a meal and wait 20 minutes (to let your food digest and get liquified and evenly dispersed) you then use the pump to remove 30 percent of your stomach contents. [I have no idea how it is able to gauge what 30 percent of your stomach contents are, but then again I don’t know how a Segway works either.] You then spray these contents into a suitable disposal apparatus such as your toilet, or if you are an animal lover, a baby birds mouth.

So why is this controversial you ask? Well, where do I start? First of all, the idea grosses people out and reminds them of bulimia (bulimia is generally considered a very bad thing). It also is offensive to those people who believe one should approach dieting from a healthy direction – with lifestyle changes that involve healthy food choices and eating habits and all that stuff. To them the idea of a quick fix approach sounds abhorrent, especially one that just seems so creepy. Some folks also express fear that this device may lead to health issues associated with classic bulimia, such as nutritional deficiencies and metabolic dysfunctions.

I think everyone should just chill out. First of all, if this device is approved it surely will be only for morbidly obese folks, and then only after classic diet and behavior counseling has proven ineffective. Mobidly obese folk are very sick and they almost always have severe diabetes and accompanying health issues that I can’t even begin to list. Right now the options for these folks are not good and usually involve some sort of bariatric surgery. Bariatric surgery is a horrible procedure and carries a frightening fatality risk. Plus, it can be absolute torture to prepare for, and even worse to recover from. This AspireAssist device on the other hand requires a relatively simple surgical procedure to install, and if needed the device can be removed quite easily and rapidly as well. And what about the risk of nutritional deficiencies and associated bulimia type issues? I don’t see the possibility of that, since you are removing stomach contents which should be homogenously distributed (if you wait the required 20 minutes after eating), and you are only removing 30 percent of the contents. It’s not really different then if you just ate 30 percent less to begin with.

So once you get over the yuck factor and think about it, AspireAssist may actually prove to be a pretty nifty and valuable medical breakthrough. Technological advancements are often met with alarm and disdain, especially if they encroach on sensitive subjects such as personal appearance and fitness. In the end though, they can come to be accepted if they fulfill their promise.

Dec

12

Homemade Steroids Making Users Sick?

By Patrick Arnold

In Panama City Florida a steroid bust was made at what appeared to be some “garage lab”. The amount of steroids seized allegedly had a street value of one million dollars (I have no idea how that is calculated but I suspect it is warped on the high side.) What made this story a bit unusual was that the steroids apparently were making people ill.

I read this story on the internet and it originated from a newspaper called The News Herald which is out of the panhandle area of florida. What is described sounds like injectable steroids, in other words, steroids dissolved in oil. Authorities claim that some of these steroids had residue stuck to the side of the vials and some had “debris” floating in them.

Residue and debris in injectable steroids sounds unclean and potentially harmful and that very well could be the case. It also could be the case that this residue and debris was precipitated steroid crystals due to the product being loaded into the oil at too high of a concentration. That may not necessarily be unclean or harmful (other than potential harm from steroids themselves), but is indicative that whoever was making the product didn’t know what they were doing. Oddly, the cops commented on the fact that the “cook plate”, which I assume means hot plate, was anything but sterile. I am not sure why a hot plate would have to be sterile for product that is put into a vial to be sterile. I bet the house the hot plate was in wasn’t sterile either.

What made this story interesting to me though was the fact that these products were producing troubling physical symptoms in many of the users. These were acute symptoms of coughing and chest pain. Authorities weren’t sure if it was the steroid in the product or something else in the product. Since I am familiar with this area I can say with relative confidence that it was likely one of two things. First of all, the steroids could have contained trenbolone acetate, which is a steroid commonly known to cause an anaphylactic type reaction in users upon injection. An anaphylactic reaction is an allergic response that comes on very quickly (seconds or minutes) after exposure to an allergen and involves symptoms such as coughing due to shortness of breath, chest pain, sweating etc. Also known to cause anaphylactic reactions are the chemicals benzyl alcohol and benzyl benzoate. These chemicals are often added to injectable preparations in small amounts, but when added in larger amounts they have been known to cause anaphylactic like reactions in people (sometimes quite severe).

It’s a very bad idea to use an oil based injectable steroid or anything that is not made under proper pharmaceutical conditions. And although the risk of infection due to sterility problems is much less than that of water based preparations, there still can be a host of other problems that can cause you some serious problems. Unfortunately the desire to use performance enhancement drugs is widespread and the current laws forbid the use of steroids and other PEDs for things other than disease. As a result, people are buying stuff from idiots that mix up Chinese steroid powder in oil in their basement.

http://www.msnbc.msn.com/id/50165912/ns/technology_and_science-space/?ocid=msnhp&pos=6#.UMjk1oPhqDc

Oct

25

Hypertension and anabolic steroids. A new pathway?

By Patrick Arnold

People familiar with the use of anabolic steroids know that water retention and hypertension (high blood pressure) are potential side effects. This is due to the fact that all androgenic hormones have the capacity to cause some sodium retention (and hence water retention) through direct action via androgen receptors in the kidneys. Furthermore, anabolic steroids that are estrogenic or can convert to estrogens can cause even more sodium retention via additional interaction with renal (kidney) estrogen receptors. So it’s often thought that an anabolic steroids propensity for water retention is related to its potency both as an androgen and as an estrogen (manifested via aromatization to estrogenic metabolites).

Confusion has often arisen however when people have noticed that some steroids – which traditional thinking tells us should not result in extraordinary water retention – end up doing just that. Steroids that should not aromatize to estrogens such as oxymetholone (anadrol) and methyl-1-testosterone are known to result in extreme water retention in some individuals. A recent paper* suggests a heretofore unmentioned explanation for this.

There is an enzyme that is localized primarily in the kidneys whose function is to protect the kidneys from circulating cortisol. The kidneys have receptors called mineralcorticoid receptors (MR’s) which are meant to bind to specific adrenal hormones (called mineralcorticoids) in the body such as aldosterone. The result of this binding is a signal to increase sodium and water retention in the body, while stimulating the excretion of potassium. This is an important mechanism to maintain fluid and electrolyte balance in the body.

A problem exists though in that cortisol can also bind activate these receptors. Cortisol is a widely circulating hormone and serves a multitude of functions throughout the body. However its intended biological functions do not include mineralcorticoid action in the kidneys, so to prevent this from happening the kidneys are rich in the enzyme 11b-hydroxysteroid dehydrogenase 2 (11b-HSD2). This enzyme deactivates cortisol by converting it into cortisone before it can bind to the renal MRs.

Certain substances can block 11b-HSD2, and that can lead to problems. One example is a constituent of black licorice known as glycyrrhetinic acid. This enzyme inhibition potential is precisely why people that consume a lot of black licorice are known to retain water and experience high blood pressure and electrolyte disturbances. Interestingly, legend has it that Genghis Khan had his armies ingest licorice while on the march to prevent thirst and dehydration. Of course Genghis Khan had no idea that 11b-HSD2 inhibition was responsible for these effects, and today many have been similarly unaware that this property might be responsible for some of the salt/water effects of anabolic steroids.

The study I referred to earlier found that many anabolic steroids indeed do share the ability to block this enzyme, and some of them are as powerful as glycyrrhetinic acid. Fluoxymesterone (halotestin) in particular was shown to be about as potent as glycyrrhetinic acid in this regard. This makes sense, since fluoxymesterone shares the same 11b-OH group as cortisol and can be oxidatively metabolized by 11b-HSD2 in an analogous manner.

The fact that fluoxymesterone serves as a substrate for 11b-HSD2 in this manner makes it a competitive inhibitor of the enzyme. Other anabolic steroids were also found to be potent inhibitors of the enzyme as well, although the mechanisms for these are not clear as they do not share the 11b-OH group.

In addition to fluoxymesterone other 11b-HSD2 inhibitor steroids of interest are oxymetholone (anadrol), oxymesterone, and testosterone. The question arises as to how relevant this enzyme inhibiton is in the real world. Fluoxymesterone is generally not associated excess water retention, but then again doses used are relatively low (20mg or less per day). In contrast, oxymetholone is well associated with excess water retention and the doses used of that are often high (50-150mg per day). So this may be a dose related phenomenon. Another question that I have is what sort of inhibition might methyl-1-testosterone have, since it seems to be the worst water retaining and hypertensive steroid ever made. Few have had decent explanations for this and perhaps 11b-HSD2 inhibition is a culprit (the study did not test this steroid).

A final point of interest to mention here is the intriguing fact that 11-ketofluoxymesterone (the metabolite formed in the kidneys as mentioned previously) is actually a stronger anabolic steroid than fluoxymesterone according to animal tests. I find that interesting because one would also expect it to generally lack the troublesome enzyme inhibition that can lead to mineralcorticoid related disturbances. Maybe if the inventors of fluoxymesterone had decided to just simply oxidize the 11b-OH group they would have ended up with a more healthy and effective steroid to sell.

*http://www.ncbi.nlm.nih.gov/pubmed/22273746

Sep

17

Breaking new research on ursolic acid shows increases in brown fat production and confirms muscle building potential

By Patrick Arnold

The most interesting health and fitness related natural compound to come around within the last decade or so has got to be ursolic acid. I have been aware of its benefits for quite some time but it wasn’t until last year that I really became excited. It was then that a landmark study was released by some University of Iowa researchers showing that ursolic acid blocked the muscle wasting effects of nerve injury and starvation, as well as increased muscle mass in healthy animals while simultaneously reducing body fat stores. I reviewed this study in a previous blog entry in case you want to refer back to it http://patrickarnoldblog.com/new-natural-anabolic-discovered/

It’s been over a year since then and another study on ursolic acid has been released by these same researchers http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3379974/. The data confirm some of the original findings as well as shed more light on how ursolic acid works in the body to build muscle and burn fat. In contrast to the first study, where normal mice were used, this study used mice fed a high fat diet. This mouse model is used to induce obesity. Since obesity is an enormous health concern in our society, any drug or natural substance that can help treat the causes or effects of obesity would be of tremendous value. In other words, researchers aren’t so interested in developing stuff for athletes and healthy people because that’s not where the bucks are at. Still, studies that utilize the mouse obesity model can be of interest and have applicability to non-obese active folks as well.

To gauge the effects of ursolic acid, the mice were split up into groups. One group just ate the high fat diet alone while the other groups ate the high fat diet supplemented with 0.14 or 0.27 percent ursolic acid. They then examined the rats after 6 weeks. Here are some of the interesting things that they saw

Muscle and Exercise

Ursolic acid increased the size of both slow and fast twitch muscle fibers. This was associated with increased Akt signalling (Akt has vital roles in biological processes such as protein synthesis and glucose uptake and metabolism). These rats had greater grip strength than control rats and could run significantly farther on a treadmill. They had slightly lower resting heart rate than controls while demonstrating no differences in blood pressure. Another interesting find is that a substance called vascular endothelial growth factor – A was substantially more active in the ursolic mice, indicating that new blood vessels were being formed to feed the growing muscle tissue.

Bodyfat and Glucose Tolerance

The mice fed the high fat diet supplemented with ursolic acid gained less weight then the control rats and had substantially less stored body fat. Their fasting blood glucose stayed normal compared to the control mice (average 74 mg/dl versus average 109 mg/dl), and their blood glucose levels after a glucose challenge also was substantially lower.

Brown Fat and Energy Expenditure
There are two types of body fat – brown fat and white fat. White fat is more or less metabolically inactive, and its purpose is mostly to store calories. Brown fat on the other hand is full of an enzyme called UCP-1 which stimulates thermogenesis (this is the same enzyme turned on by DNP). Brown fat is rich in blood supply and essentially burns calories and keeps you warm. The researchers found that the ursolic supplement mice had a lot more brown fat, and not surprisingly they were much more resistant to the cold then the control rats.

The ursolic supplemented mice had higher levels of energy expenditure. Even though they ate more food than the control mice, the ursolic mice weighed less – with the difference in weight made up in body fat. This was not an acute effect however and was only seen after chronic administration of ursolic acid. This is entirely consistent with the fact that it required time for the growth of muscle and brown fat to burn the extra calories, and was not due to some immediate stimulant effect.

Ursolic Acid Supplementation

This latest study just adds to the impressive evidence behind the amazing bodybuilding and overall health potential of ursolic acid. Ursolic acid as a supplement has become more and more popular over the last year or so since the evidence first started pouring in on the stuff. It is usually sold in the form of an extract from herbs such as rosemary or loquat leaf. This form has proven to be less than stellar however in the feedback users have been giving. Results have been hit or miss for the most part.

I noticed this high variability in results and less than anticipated feedback early on, and I was quite certain it was due to the terrible solubility of the compound. It basically repels water and is very insoluble in the sort of solvent systems that are similar to the properties of the lining of your gastrointestinal system. If you couple that with the likelihood it is metabolized extensively upon liver first pass, you end up with very poor bioavailabilty. In fact, research suggests that less than one percent of orally ingested ursolic acid actually gets into your system.

I solved this problem however. For the past several months I have synthesized and played with derivatives of ursolic acid that have solubility and dispersability properties magnitudes better than straight ursolic acid. I have found that delivering these derivatives (which simple break down quickly in the body to ursolic acid after being absorbed) via a topical formulation leads to the sort of body fat loss and muscle mass increases in human subjects that we would expect to see from the published mice studies.

The compound I have settled on as the best has absolutely amazing solubility compared to straight ursolic acid. It is called Arginine Ursolic Acetate and this is its chemical structure.

In the body this compound breaks down rapidly to acetic acid (a dietary fatty acid), l-arginine (a dietary amino acid), and ursolic acid. Although I have never (yet) measured blood levels of ursolic acid to prove that this method delivers the compound way better than regular extract capsules, the fact that almost everyone that has tried when formulated topically gets amazing results sort of speaks for itself.

So there you go. If you weren’t excited about ursolic acid before then you should be now. And if you want to try the patent pending form that I worked my butt off to perfect then you can by clicking here

http://www.prototypenutrition.com/ProductDetails.asp?ProductCode=UR

Aug

2

The New Steroid Legislation as seen by Rick Collins, JD, CSCS

By Patrick Arnold

The New Designer Steroid Bill and YOU:

Questions and Answers with Rick Collins

Q: What is the “Designer Anabolic Steroid Control Act of 2012”?

A: It’s a Senate Bill (SB 3431) introduced by Senators Orrin Hatch (R-Utah) and Sheldon Whitehouse (D-R.I.) and referred to the Judiciary Committee. If passed by Congress, it will amend the Controlled Substances Act to more aggressively regulate steroidal substances being sold as dietary supplement ingredients. The clear intent is to remove remaining “prohormone” products from the market and prevent new ones from being introduced. The bill would take such past or present supplement products as ATD, 6-oxo, 6-bromo, Furazadrol, Halodrol, Havoc, and Tren and legally classify them as anabolic steroids and Controlled Substances. Here’s what Sen. Whitehouse said in introducing the bill on July 25th, 2012:

“… I am pleased to join Senator Hatch in introducing the bipartisan Designer Anabolic Steroid Control Act of 2012. This measure will help keep American children and families safe from dangerous designer drugs that masquerade as healthy dietary supplements. This legislation is based on Senator Specter’s work in the previous Congress, and I thank him for his leadership on this issue.

Doctors and scientists have long recognized the health hazards of non-medical use of anabolic steroids. For that reason, Congress has previously acted to ensure that these drugs are listed as controlled substances. Nonetheless, according to investigative reporting and Congressional testimony, a loophole in current law allows for designer anabolic steroids to easily be found on the Internet, in gyms, and even in retail stores.

Designer steroids are produced by reverse engineering existing illegal steroids and then slightly modifying the chemical composition, so that the resulting product is not on the Drug Enforcement Administration’s, DEA, list of controlled substances. When taken by consumers, designer steroids can cause serious medical consequences, including liver injury and increased risk of heart attack and stroke. They may also lead to psychological effects such as aggression, hostility, and addiction.

These designer products can be even more dangerous than traditional steroids because they are often untested, produced from overseas raw materials, and manufactured without quality controls. As one witness testified at a Crime Subcommittee hearing in the last Congress, ‘all it takes to cash in on the storefront steroid craze is a credit card to import raw products from China or India where most of the raw ingredients come from, the ability to pour powders into a bottle or pill and a printer to create shiny, glossy labels.’

The unscrupulous actors responsible for manufacturing and selling these products often market them with misleading and inaccurate labels. That can cause consumers who are looking for a healthy supplement–not just elite athletes, but also high school students, law enforcement personnel, and mainstream Americans–to be deceived into taking these dangerous products.

Loopholes in existing law allow these dangerous designer steroids to evade regulation. Under current law, in order to classify new substances as steroids, the DEA must complete a burdensome and time-consuming series of chemical and pharmacological testing. As a DEA official testified before Congress: ‘in the time that it takes DEA to administratively schedule an anabolic steroid used in a dietary supplement product, several new products can enter the market to take the place of those products.’’

The Designer Anabolic Steroid Control Act of 2012 would quickly protect consumers from these dangerous products. First, it would immediately place 27 known designer anabolic steroids on the list of controlled substances. Second, it would grant the DEA authority to temporarily schedule new designer steroids on the controlled substances list, so that if bad actors develop new variations, these products can be removed from the market. Third, it would create new penalties for importing, manufacturing, or distributing anabolic steroid’s [sic] under false labels.

Senator Hatch and I have worked closely with a range of consumer and industry organizations to ensure that this legislation would not interfere with consumers’ access to legitimate dietary supplements. I am pleased that the measure has been endorsed by the United States Anti-Doping Agency, the Alliance for Natural Health, the Council for Responsible Nutrition, the American Herbal Products Association, the Natural Products Association, the Consumer Health Products Association, and the United Natural Products Alliance.

I thank these organizations for their support, and look forward to working with them, with Senator Hatch, and with colleagues from both sides of the aisle to enact this common sense measure into law.”

Q: Is the bill specific in naming the substances to be added to the list of anabolic steroids?

A: The “Discussion Draft” of the bill that I reviewed would specifically add 27 chemical compounds to the list of substances defined as anabolic steroids in Title 21 of the U.S. Code [21 USC 802(41)]. The bill presents the chemical nomenclature for these substances. Some of the chemical names listed, according to steroidal supplement guru Patrick Arnold, contain errors or refer to compounds that may actually not exist. But any minor mistakes aside, it seems that the drafters of the bill extensively canvassed the supplement market and perhaps even the Internet message boards in an effort to identify and specifically name as many compounds as possible. This isn’t the first time that Congress has expanded the list of anabolic steroids. The original list, compiled in 1990, was amended in 2004 to include androstenedione and a variety of other steroidal products. The DEA later issued a Final Rule (http://www.gpo.gov/fdsys/pkg/FR-2009-12-04/pdf/E9-28572.pdf), effective January 2010, classifying three more compounds as anabolic steroids (boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione, along with their salts, esters and ethers). Then the DEA last year published a notice of proposed rulemaking to add yet two more steroidal compounds, prostanozol and methasterone (marketed as Superdrol), along with their salts, esters and ethers, to the list. The Final Rule on these two was issued on July 30th, 2012 (http://www.gpo.gov/fdsys/pkg/FR-2012-07-30/pdf/2012-18495.pdf), effective August 29th, 2012. This new bill just follows up by adding a whole bunch more (although now a moot point, it includes the recently scheduled prostanozol and Superdrol) … and by design, misses very few.

Q: What about steroidal substances that are not on the list?

A: The bill changes the way unlisted steroidal compounds are dealt with. It says that “a drug or hormonal substance (other than estrogens, progestins, corticosteroids, and dehydroepiandrosterone) that is not listed … and is derived from, or has a chemical structure substantially similar to, 1 or more [listed] anabolic steroids [is considered an anabolic steroid] if … [it] has been created or manufactured with the intent of [promoting muscle growth or having pharmacological effects like testosterone or] has been, or is intended to be, marketed or otherwise promoted [to suggest it will promote muscle growth or have pharmacological effects like testosterone]. Notice that there’s no proof requirement that the substance actually promote muscle growth or act like testosterone pharmacologically – only that it’s created, manufactured, marketed or promoted with the intent of doing so. So, for supplement industry purposes, a company that markets any product that is derived from or has substantial chemical similarity to a listed anabolic steroid and is also created or marketed to build muscle or have a pharmacological effect like testosterone is marketing an anabolic steroid. An interesting question arises in the following theoretical scenario: Company A markets an ingredient derived from a listed anabolic steroid for health and wellness purposes, and the ingredient has neither anabolic nor androgenic effects. Company B markets the same ingredient but makes the claim, falsely, that the ingredient builds muscle. If Company B is prosecuted and convicted for marketing the ingredient as an anabolic steroid, where does this leave Company A? While it would seem reasonable that the ingredient is an anabolic steroid only with respect to Company B, the issue is not addressed in the language of the bill.

Q: Are there any exemptions provided in the bill?

A: Yes. Unlisted steroidal compounds that are herbs or botanicals are exempted. So are concentrates, metabolites, and extracts of an herb or botanical, or a constituent isolated directly from an herb or botanical. This provision was drafted as an acknowledgement to the current position of the Food and Drug Administration (FDA) articulated with respect to New Dietary Ingredients (NDI’s): that a compound is a “constituent” of a botanical only if it is isolated directly from it, and not if it is instead synthetically created in a lab. The bill further connects the Controlled Substances Act with the Dietary Supplement Health and Education Act (“DSHEA,” a part of the Food, Drug, and Cosmetic Act) by requiring that any exempted substance must be a “dietary ingredient” under DSHEA. And the bill puts the burden of DSHEA compliance on the marketer, by providing that anyone “claiming the benefit of an exemption [has] the burden of going forward with the evidence.” In other words, somebody arrested for selling an anabolic steroid whose defense is that it is an exempted constituent would have the burden of showing evidence of DSHEA compliance.

Q: Does the bill make it easier to add new unlisted substances to the list?

A: It does, by amending a different section of Title 21 [21 USC 811] to provide a fast-track for scheduling. The Attorney General may issue a temporary order, to take effect 30 days after publication, adding a substance to the list if it meets certain criteria. The temporary order “is not subject to judicial review” and a permanent order could be simultaneously sought. But the bill also provides that an unlisted steroidal substance can be considered an anabolic steroid if it’s determined to meet the criteria of an anabolic steroid “in any criminal, civil, or administrative proceeding arising under this Act.” So, while the Attorney General has the power to declare substances to be anabolic steroids through the rulemaking process, unlisted substances can nevertheless be considered to be anabolic steroids without prior rulemaking notice if it’s proven in a court of law, such as during a criminal prosecution of a supplement company or its principals. But the bill also makes it easier for the Attorney General to add new compounds because it changes the criteria and tosses out the rigorous scientific inquiry currently required.

Q: How would the criteria for administrative action change under the proposed new law?

A: Under current requirements, the DEA has to extensively examine peer-reviewed published literature and sometimes even undertake its own pharmacological assay studies to determine if a compound has androgenic and anabolic activity similar to testosterone. This can be a huge, lengthy, complicated endeavor, and the DEA has been far from wild about it. For example, back in September 2009, Joseph Rannazzisi, Deputy Assistant Administrator at DEA’s Office of Diversion Control, testified before the Crime Subcommittee at the hearing (“Body Building Products and Hidden Steroids: Enforcement Barriers”) referenced this month by Sen. Whitehouse in introducing the bill. Mr. Rannazzisi expressed the hurdles imposed by the current law, citing as an example the difficult process of scheduling boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione which was, at that time, in its final stages. He also testified that a review of three (3) additional compounds – methyldrostanolone (methasterone), prostanozol, and adrenosterone (misspelled adrenostreone in his written statement) – had begun. But although three compounds were reviewed, only two were scheduled. Neither the notice of proposed rulemaking in November 2011 nor the Final Rule issued in July 2012 referenced adrenosterone, a compound sold under the name “11-oxo.” Were there problems proving some aspect of the requirements? We don’t know, and the implications from this are open to debate (note also that the substance is also not listed among the specific compounds in the new bill). In any event, under the new definition of an anabolic steroid, the process for scheduling is much easier. If the compound is derived from, or has a chemical structure substantially similar to a listed anabolic steroids, and it’s not an estrogen, progestin, corticosteroid or DHEA, then it’s considered an anabolic steroid merely if it’s been created or manufactured with the intent of being anabolic or androgenic or if it’s marketed or promoted to suggest that it’s anabolic or androgenic. The new definition offers an enormous reduction in the DEA’s burden to schedule a new steroid.

Q: Weren’t many of these supplement products already illegal under the Food, Drug, and Cosmetic Act?

A: Yes. Many of these substances were synthetically created compounds and did not meet the criteria to be sold as dietary supplements under DSHEA. Since they were not DSHEA compliant, they were unapproved and mislabeled “drugs” and the FDA had the authority to investigate and bring charges for federal prosecution. Until recently, however, many in the supplement industry didn’t understand the criminal penalties for non-DSHEA compliance, or didn’t take the threat seriously. But that has changed since a number of sports nutrition companies were prosecuted for selling prohormone products in the wake of the execution of a search warrant on a distributor’s Boise, Idaho facility back in 2009. Some of the same substances now being added to the list of anabolic steroids under the Controlled Substances Act were already declared illegal drugs under the Food, Drug, and Cosmetic Act (FD&CA) … and the companies selling them were prosecuted federally and convicted. The new bill, however, gives the DEA – often viewed as more aggressive at enforcement than the FDA – the authority to take action. Also, by classifying these substances under the Controlled Substances Act, the new bill escalates the severity of potential punishments.

Q: What does the bill say about sentences for steroid crimes?

A: The bill directs the United States Sentencing Commission to “review and amend the Federal sentencing guidelines.” The last time Congress directed this, the Commission brought the hammer down and greatly escalated the punishments for steroid trafficking crimes by re-calculating the way steroids were quantified. As of 2006, injectable and oral steroids became quantified for punishment in a 1:1 ratio to other Schedule III drugs, resulting in a twenty-fold measurement increase for injectable steroid units and a whopping fifty-fold increase for oral steroid units. One “unit” of an oral steroid became one pill, tablet or capsule rather than fifty; one unit of a liquid steroid was reduced to .5ml rather than 10ml, and steroids in other forms (“e.g., patch, topical cream, aerosol”) were to be reasonably estimated based on a consideration of 25mg as one unit. We don’t know exactly what the Commission will do if this new bill passes, but the bill specifically directs that for steroid products where dosage cannot be readily ascertained, such as powders or topical creams, that “the sentence shall be determined based on the entire weight of the mixture or substance.” So, a person trafficking a kilogram of pure testosterone powder would be at the same federal sentencing level as the person who was selling a product that contained a small or even trace amount of testosterone.

Q: What does the bill say about the way products are labeled?

A: The bill introduces a whole new theory by which to prosecute these cases by making it a crime to import, export, manufacture, distribute, dispense, sell, offer to sell, or possess with intent to manufacture or sell any anabolic steroid, or any product containing an anabolic steroid, unless it bears a label clearly identifying the anabolic steroid by accepted (IUPAC) nomenclature. This provision would apply to manufacturers who use deceptive or “creative” ingredient labeling to conceal that the product is an anabolic steroid. It would also apply to distributors and retailers who know, intend, or have reasonable cause to believe that the product contains an anabolic steroid. Criminal penalties can be up to 10 years imprisonment and massive fines (up to $2.5 million on corporations). Civil penalties can be up to $500,000 per product violation for importers, exporters, manufacturers and distributors. Even retailers can be hit with a $25,000 penalty per product violation (and each package size, form, or differently labeled item is a separate product).

Q: What impact would this bill have on consumers?

A: The bill would have a huge impact on consumers. While marketing prohormones that are currently illegal under DSHEA and the FD&CA subject the marketers to criminal sanctions, consumers don’t face charges. Simple possession itself is not illegal. All that changes when a compound becomes classified as a controlled substance. By reclassifying these compounds into controlled substances, this bill criminalizes the consumers as well as the marketers (the DEA’s Final Rule on prostanozol and Superdrol, once effective, will do this on those two compounds). Being in simple possession of a compound that is a controlled substance is a federal crime – a federal misdemeanor that carries with it up to a year of incarceration. But it likely won’t stop there. If the bill passes, it’s quite probable that individual states will view what Congress did as an important step in protecting the public, especially children, and will seek to amend their own laws to be consistent with the new federal law. In some states, though, simple possession of an anabolic steroid is a felony, not a misdemeanor, and in those states the simple possession of any of these compounds would be a felony. If states follow suit, a person caught during a car stop with a single capsule of 6-bromo, for example, would be charged with either a misdemeanor or a felony (depending on his or her state’s law). An old bottle of Superdrol sitting in a gym bag would be like illegally having a bottle of Vicodin.

Q: Do you think this bill will achieve the intended purposes of Congress?

A: Unlike the poorly conceived and drafted 2004 amendment to the Anabolic Steroid Control Act, this bill shows an investment of considerable effort and thought. It’s clear that the intent behind it is to eradicate steroidal ingredients from the retail supplement market. This bill has the potential to accomplish that. It even requires the Administrator of the DEA to keep Congress in the loop by reporting to them every 2 years on what new steroids have been scheduled. Of course, the bigger picture is unclear. Will consumer demand for steroidal substances that may build muscle disappear? Or will the reclassification of these items and their removal from the dietary supplement market lead to the creation of a black market for them … or to an increased demand for the traditional pharmaceutical anabolic steroids already on the black market? The realities of demand and supply and our experience with alcohol Prohibition would suggest that legislative efforts like this one don’t entirely eliminate problems but instead may push them underground. Time will tell.

Q: What do you predict for this bill?

A: Senator Hatch is viewed as a stalwart advocate for dietary supplements. So, when he sponsors legislation to restrict the industry, many in Congress will see it as something that sorely needs to be done. The bill has received the overwhelming support of the large industry trade groups and there is no organized opposition. Unless there’s some unexpected curveball tossed out, or Earth is hit by an asteroid, there’s a high likelihood the bill will pass. For future updates and analysis, visit www.supplementcounsel.com and www.steroidlaw.com or follow me on Twitter (@RickCollinsEsq) and at Facebook.com/RickCollinsOnline.

Rick Collins, JD, CSCS [www.rickcollins.com] is the lawyer that members of the bodybuilding community and nutritional supplement industry turn to when they need legal help or representation. He and his firm represent dietary supplement companies nationwide, and he has personally defended steroid criminal charges from coast to coast. He can be reached at 516-294-0300. [© Rick Collins, 2012. All rights reserved. For informational purposes only, not to be construed as legal or medical advice.]

2012 Designer Anabolic Steroid Control Act