Review: Molecular Nutrition’s X-Factor: Is Arachidonic Acid A Potent Anabolic Compound?
Molecular Nutrition’s X-Factor is yet another entry in the race for a non-hormonal, anabolic compound. It’s a simple supplement with only one ingredient: arachidonic acid. According to Molecular Nutrition’s web site:
“Clinically tested at Baylor University for safety and effectiveness, Anabolic X-Factor™ is the world’s first patented hypertrophic catalyst. By enhancing the storage of arachidonic acid in exercised muscles, X-Factor drastically amplifies the body’s sensitivity and responsiveness to resistance training. This means faster and more profound increases in muscle size, strength, even the rate of lipolysis (fat loss).”
Promises, promises…but can X-Factor deliver?
Let’s start from the beginning: what is arachidonic acid, and what does it do?
Arachidonic acid is an omega-6 fatty acid formed in the body from linoleic acid—an essential fatty acid found in nuts, seeds and vegetable oils. This process is similar to the one that the omega-3 alpha-linolenic acid (found in flax, canola and hemp oils) goes through to be converted to EPA (eicosapentaenoic acid) and DHA (docosahexaeonoic acid). And like fatty fish and fish oils, which contain pre-formed EPA and DHA, pre-formed arachidonic acid is found in animal foods like red meat and eggs.
EPA, DHA, and arachidonic acid (AA) are incorporated into cell membrane phospholipids. When released, they can form a number of biologically active metabolites known collectively as “eicosanoids.” In general, the omega-3 based eicosanoids tend to be anti-inflammatory, while the omega-6 based eicosanoids are pro-inflammatory.
Many bodybuilders supplement extensively with omega-3 fatty acids from flax or fish oils, and avoid omega-6 sources for precisely this reason…to limit inflammation, which is considered “bad.” The truth is a bit more complicated than that, however. Inflammatory reactions aren’t all “bad.” They play an important role in immunity, for example. They also assist in the healing of injured or traumatized tissues. The reality is that some inflammation is a good thing. It’s not a process you want to shut down completely.
So how can a compound that contributes to inflammation help people get bigger, stronger and leaner? The answer is somewhat complicated, so bear with me.
As it turns out, inflammation also plays a role in muscle protein synthesis (MPS). This is supported by some rather interesting research in exercising humans that showed ibuprofen and acetaminophen completely abolish the post-exercise increase in MPS when taken in recommended doses. The study authors concluded that “…long-term use of these drugs may inhibit the normal hypertrophic response to resistance training.”
How do these anti-inflammatory drugs interfere with MPS? Both ibuprofen and acetaminophen inhibit the activity of the cyclooxygenase, or COX, enzyme. The COX pathway is used to produce a class of eicosanoids called prostaglandins. Earlier animal research showed that two specific prostaglandins produced by the COX pathway, PGF2a and PGE2, exert a significant influence on protein synthesis and breakdown, respectively.
Both PGF2a and PGE2 are produced from arachidonic acid.
In a second experiment on the effects of ibuprofen and acetaminophen following exercise, the most profound impact of these drugs was on the production of PGF2a, which was increased by 77% in the placebo group, but depressed in the ibuprofen (-1%) and acetaminophen (-14%) groups.
In other words, no PGF2a, no post-exercise MPS. Suppression of PGF2a is a bad idea.
Does this mean increasing PGF2a is a good idea? This is the idea behind supplementing with X-Factor. The rationale is certainly promising. Arachidonic acid is stored in cell membrane phospholipids. Cell damage—such as the type induced by resistance exercise—increases the release of arachidonic acid and COX activity. Thus, increasing the amount of stored arachidonic acid could conceivably elevate PGF2a production and enhance post-exercise MPS.
There may be other potential benefits as well. Some recent, preliminary research in mice indicates that arachidonic acid may also have anti-obesity effects, due to its role in downregulating stearoyl-CoA desaturase (SCD1)—an enzyme in the liver. High SCD1 activity has been implicated in the development of metabolic disorders such as diabetes, obesity and cardiovascular disease. Suppressing SCD1 activity might help people lose fat, or at least resist fat gains.
So Molecular Nutrition’s claims of increased muscle mass/strength and lipolysis certainly have some theoretical justification. For my money, however, I’d like more than theory—which brings us back to the question at the start of this review. Does X-Factor actually work?
I’ll give props to Molecular Nutrition: they’re one of the few supplement companies willing to put its product to the test. In 2006, researchers associated with Baylor University conducted a controlled study on X-Factor. The researchers were scrupulous about following directions, and imposed the following conditions on their subjects:
- increased calories. Study subjects were instructed to increase their daily intake by 500 kcal/day above baseline.
- increased protein. Study subjects increased their intake to 2 g/kg/day, using additional protein from commercial supplement packets.
- avoidance of foods and supplements containing omega-3 fatty acids (which compete with arachidonic acid for phospholipid storage).
All subjects were experienced trainees who consumed 4 capsules of X-Factor per day, and performed a 4 day/week resistance-training program.
There are two versions of the results. One appears on Molecular Nutrition’s web site, and highlights the preliminary poster abstracts and the positive results of the study. There were some increases in peak power for the Wingate anaerobic capacity test, for example, along with a decrease in one inflammatory marker, interleukin-6. There were no adverse side effects seen. So far, so good.
You have to read the full paper, however, for the depressing conclusion.
AA supplementation during resistance-training may enhance anaerobic capacity and lessen the inflammatory response to training. However, AA supplementation did not promote statistically greater gains in strength, muscle mass, or influence markers of muscle hypertrophy.
In other words, the study subjects didn’t get much stronger, bigger, or leaner as a result of taking X-Factor. Moreover, PGF2a levels did not increase in the X-Factor group as expected, despite a small, but significant, increase in PGE2. Overall, X-Factor was a flop.
On the flip side, there are a number of enthusiastic X-Factor users who report positive results, which is hard to reconcile with the study results.
In some cases, this could simply be the net result of the many changes people tend to make when using a supplement they believe will be beneficial.
They tighten up on their diets and work harder in the gym…then give the credit to the supplement for their improvements.
There may be more to it than that, however. At the end of the X-Factor study, the authors wrote:
“Additionally, whether some athletes may respond better to AA supplementation than others should be explored.”
Is it possible that there was a difference between the study subjects and more dedicated bodybuilders that could explain the discrepancy between the study results and user reviews?
For what it’s worth, the study subjects appear to have been average college students with a gym habit, judging from their body compositions. It’s also likely they had pretty average diets too, judging from their protein intake prior to supplementation (1.3 g/kg).
It’s well-known that the typical Western diet – while not especially rich in pre-formed arachidonic acid – is very rich in linoleic acid, which can be used to form arachidonic acid. Linoleic acid was tracked in the study, but not restricted, nor was the average intake reported. Thus, it’s possible that the two groups weren’t that far apart in their intakes of arachidonic acid, at least indirectly.
In contrast, dedicated, goal-oriented trainees are very scrupulous about their diets…perhaps too much so. As noted above, many restrict sources of “bad” omega-6 fats, and consume large amounts of omega-3 fatty acids, which compete with arachidonic acid for inclusion in membrane phospholipids. They are likely to have lower arachidonic acid stores to begin with, so it’s possible they might derive a much greater benefit from a cycle of supplementation/omega-3 restriction than your average gym rat.
This is, of course, sheer speculation on my part, but it seems to fit the profiles of the bodybuilders I work with—some of whom also think well of X-Factor.
So is X-Factor worth a try?
There’s certainly a nice theory behind it, and there are success stories, although these are anecdotal. My “take” is that it could be useful for certain people, as outlined above. I also think it has a potential use (in lower amounts) as a general purpose supplement, for people who have limited intake of omega-6 fatty acids in their diets. Arachidonic acid is an important metabolite, after all, and should not be considered a “bad” fat, if it isn’t consumed in excess by healthy people.
|Summary of X-Factor|