Don't Kill the Messenger

Complexity – Simplicity – Ubiquity

The complexity of the human body is incredible. Maybe it's not necessarily the sheer complexity, but the complexity in spite of utter simplicity.

Think about it. Every piece (protein) in your body is created from 22 amino acids. These amino acids are coded for and sequenced by RNA and DNA, which contain only 4 different (5 if you count uracil) building blocks (or nucleotide bases). Four building blocks to create your entire body... Amazing! The use of simple ubiquitous pieces is a reoccurring theme throughout the body that extends far beyond DNA and amino acids.

I'd be remiss if I didn't mention one of the chemical progeny of fish oil as another example. EPA, as well as the omega-6 fatty acid arachidonic acid, is readily converted to short lived powerful hormones called eicosanoids. Eicosanoids can act in practically every cell in the body. Again, 1-2 compounds that are extremely powerful and boast utter ubiquity.

You may also see a trend here. Amino Acids, EPA, and arachidonic acid are extremely important to the body, and learning to strategically use them – and in the case of arachidonic acid, minimize their harmful characteristics – is essential not only to health but the development of a lean muscular physique (ultimately the reason you visit this website).

If you're following my line of thinking, then the next step would be to ask what other ubiquitous and powerful compounds in the body can be manipulated? That's what I'd like to explore with you next though an examination of what I believe to be one of the most important compounds in the human body.

You have to love a molecule that can increase the release of stored fat (lipolysis) and bolster Testosterone levels. Right?

What magical, almost too-good-to-be-true compound am I talking about?

cAMP is what is known as a second messenger. It acts just as its name implies. First, a signally molecule (the "first messenger") will bind to a cell surface. This will activate a signally pathway that ultimately upregulates cAMP production and then cAMP goes off and makes things happen (the release of stored body fat, the increase in Testosterone, you know the good stuff).

How can we get more cAMP in our lives?

Before we get into ways in which your can increase cAMP, you need to be aware of the most powerful killer of cAMP there is... insulin.

Insulin is truly the body's sharpest double-edged sword. It wields all the benefits of increased protein synthesis and muscle growth, but if you let insulin levels get too high, it will stop fat loss in its tracks like Nancy Pelosi does George W. When insulin is high, that means cAMP levels are going to be low and visa versa (this is why nutrient timing and strategic carbohydrate use is so important).

You can increase levels of cAMP by increasing the production or by reducing breakdown.

And here are ways to do both.

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1. Caffeine. This is the cheapest and easiest way to increase cAMP levels by preventing the breakdown of cAMP. Caffeine inhibits an enzyme called phosphodiesterase, which is responsible for ruining your fat burning party and breaking down cAMP.
2. Fish Oil + GLA. This combination leads to increased production of cAMP via Prostaglandin E₁ (PGE₁). As shown in the picture below, GLA can be converted to either Arachidonic Acid or PGE₁. The fatty acids in fish oil compete for enzymes with arachidonic acid, allowing for more GLA to become PGE₁. Along with your daily dose of Biotest's Flameout® (2.4 grams EPA/DHA), you should take between 50-150mg of GLA.
3. Forskolin. Forskolin could be the grand daddy of them all when it comes to increasing cAMP. Interestingly enough, forskolin has been around for a while. Studies demonstrating forskolin's ability to increase cAMP go back to the early 80's.

Long time T-Nation readers should be familiar with forskolin as Cy Willson was extolling its benefits as a fat loss agent back in 2002:

"This substance, in theory, should work since its ability to stimulate cAMP production (which increases lipolysis) has been well documented. However, does this mean it'll actually work in humans? It looks hopeful at this point and forskolin is getting a reputation for being a natural, non-suppressive thyroid booster."

Like most herbals, there aren't mounds of good randomized clinical trials regarding forskolin (the NIH isn't jumping up and down waiting to fund forskolin studies, but maybe they will in the near future). There are a few, though.

The first study (Bristow MR et al, 1984) looked at the effects of forskolin on human heart tissue. This study found that forskolin was able to increase cAMP levels 4.82 times more than baseline levels. The importance of this study is that it shows forskolin can increase cAMP in human tissue.

The second study (Litosch I et al, 1982) looked at forskolin's ability to increase cAMP in adipocytes. We already knew from the previous study that it worked in muscle cells but will it work in fat cells? This 1982 study found that in rat adipocytes forskolin increases cAMP in both isolated and intact cell (this is good).

The researchers also found that forskolin not only increased lipolysis, but that this change in cAMP and lipolysis was reduced by insulin. This previous sentence shows that 1) forskolin increases the adipocyte's ability to liberate stored fat and 2) forskolin's ability to increase cAMP can be reduced by insulin and thus if your diet is crap, then you won't get to reap the full benefit of forskolin supplementation.

Now let's get into the clinical trials. Unfortunately, 3 of the 5 trials that involve forskolin consist of female subjects. The problem with this is that the full Testosterone boosting capability of forskolin probably can't be analyzed effectively in females.

But we'll work with what we have. Of the 5 trials (Bhagwat AM et al, 2004; Badmaev V et al, 2002; Kreider R et al, 2002; Tsuguyoshi A, 2002; Godard MP et al, 2005), 4 showed forskolin's ability to decrease body fat while the 5^th only showed a reduction in body mass (I wasn't able to get my hands on this last study to see what was going on).

TC has previously discussed the findings of the most recent forskolin study published in The Journal of Obesity Research. This is the best study to look at, and no, not just because it had a positive result. Obesity Research is by far the most reputable journal that any of the forskolin clinical trials have been published in and the researchers covered all the important areas – Testosterone, body composition, metabolic rate, bone density, and even blood pressure (I forgot to mention that forskolin has blood pressure lowering effect due to increased vasodilation).

I won't go into the details of this study since TC wrote a whole article on it, but here are the highlights:

Fat Mass

The colforsin group lost 4.52 kilograms (9,94 pounds) of fat, plus or minus 5.74 kilograms, while the placebo group lost only 0.51 kilograms (1.12 pounds), plus or minus 1.91 kilograms.

Lean Body Mass

The colforsin group gained 3.71 kilograms of lean body mass (8.162 pounds), plus or minus 4.07 kilograms, while the placebo group gained 1.57 kilograms (3.45 pounds), plus or minus 2.56 kilograms.

Testosterone

The Testosterone of the colforsin group rose 33.7 percent, while it decreased 18.35 percent in the placebo group.

Carbolin-19® vs. Forskolin

I'm sure you've always wondered what the difference is between regular forskolin and Carbolin-19®. I was lucky enough to have Cy Wilson break down the differences to me a couple weeks ago and here's what I found out.

If you're going to buy forskolin, you actually end up buying Coleus forskolii that's been standardized for forskolin. It is usually standardized for 10% forskolin (what they use in research studies), but I have seen products standardized as low as 1%. Carbolin-19® isn't standardized for anything, it is the extract. This is like the difference between cod liver oil and pharmaceutical grade fish oil.

The second problem lies in forskolin's structure. We know from the heart and adipocytes studies that forskolin works once it gets into the cells. Getting it past the liver is the problem.

It contains two hydroxyl groups that are not only susceptible to oxidation, but during first pass metabolism, they can cause forskolin to be flagged down as a xenobiotic by the liver and terminated.

In Carbolin-19®, ethylcarbonate esters are added to these problematic functional groups.

The idea behind this is that the masking of the hydroxyl groups with ethylcarbonate esters will lead to an improved bioavailability by getting it through the liver while maintaining its potency (the added hydrophilicity helps too). So with Carbolin-19® you're getting a vastly more pure, more potent form of forskolin and consequently, elevated metabolism , possibly additional muscle gain (at least partly through elevated Testosterone levels), and in general, better body composition.

Note from Author: Neither TC or Tim asked me to write this article. Nor did I receive extra compensation for writing about this topic. I happen to be personally interested in the mechanism and effectiveness of forskolin and Carbolin-19®. So please save the comments about this being an advertorial.