The scientific method is meant to be a circle, a continuous cycle of:
It's an imperfect system, and there are many issues, including:
- flaws in study design (ie. small sample size)
- data mining / cleaning / fabrication
- unwarranted conclusions
- the failure to publish all details / results
- the failure to publish negative findings
- inappropriate citing of previous research
Many of these issues could be addressed by careful editing of article submissions, a topic that I plan to cover in a future post. For now, I want to discuss the influence of the food industry in nutrition research. The inspiration for this post came from a colleague's review of a study by Bassaganya-Riera et al. on punicic acid, the main fatty acid (or fat) found in the arils (or seeds) of pomegranates .
I'll begin with the bad news - nutritionists haven't been entirely honest with you. We often group nutrients together based on physiochemical properties with full knowledge that they include a broad range of compounds that are not therapeutically equivalent. However, consumers cannot be expected to differentiate between beta-glucans and fructo-oligosaccharides (both soluble dietary fibers), or alpha-linolenic acid and docosahexaenoic acid (both omega-3 fatty acids), so we just let them believe they are all the same - rest assured, they aren't.
With this in mind, lets discuss punicic acid (depicted above). As you can see, it is 18 carbons long, with 3 sites of unsaturation (double bonds). It makes up the majority of the fatty acids (~75%) in pomegranate seed oil, and is being investigated in this study for "anti-inflammatory" properties for the prevention of inflammatory bowel disease (IBD). I have circled the double bond that is in trans orientation, and is responsible for its designation as a trans fat.
Yes, it belongs to the family of dreaded "trans fats" that are being banned in supermarkets and restaurants (and with good reason). But this is a different trans fat - one that is found "naturally" in the food. Both milk and meat contain another group of "natural" trans fats, collectively known as conjugated linoleic acid (CLA), which are coincidentally also believed to have health-enhancing properties. The more commonly known trans fats that are linked with several risk factors for coronary heart disease are actually a subset of trans fatty acids that are man-made, usually through a chemical process called hydrogenation. But, I digress.
The study randomized mice to two separate diets, which differed only in fat composition - fat provided about 15% of total calories, 86% of which came from soybean oil. The remaining 14% was either linoleic acid (control group) or pomegranate oil (treatment group). This is the foundation of an experimental study, the assignment of the exposure of interest while attempting to keep all other variables similar between groups. When this is done right, any differences can be assumed to have been "caused" by the exposure.
According to the authors, "the optimal doses of PUA included in these diets were the result of time course and dose titration studies designed to elucidate the optimal anti-inflammatory efficacy of PUA performed previously (data not shown)". I'm admittedly not loving the lack of transparency in that process - moving on.
Interesting that the "optimal dose" was 14% of total fat intake - lets translate:
If a person consumes 2,000 calories per day, and 30% of my calories comes from fat (this is a low fat diet by Canadian standards), then I am consuming 600 calories as fat. There are 9 calories per 1 gram of fat, so I would be consuming ~67 grams of fat. If 14% of this fat was from pomegranate oil, then I would need to consume roughly 9 grams of pomegranate oil every day. This amount could quite conceivably be consumed in a supplement, although you would likely need to take 6-9 of them (1-1.5 grams each) for them to be swallowable by a human.
Equally important in this process is the choice of reference group for comparison. There are many options available, and rarely is there is a clear best choice when it comes to nutrition. In the case of inflammation, certain fats are better than others. Arguably, the most well-studied fat is the pro-inflammatory omega-6 fatty acid, linoleic acid, which is also the major fatty acid in soybean oil. Anyone who studies nutrition knows this, begging the question, why would you design a study that uses soybean oil as your background diet and linoleic acid as your comparison group? The answer is simple - effect size.
Statistical tests that look for differences between groups take into consideration three things: a) variance, b) sample size, and c) effect size. Effect size is the absolute difference between the two groups. So, if I really wanted to demonstrate that my treatment was effective, I would compare it to the worst possible substance that I could reasonably get away with, thus maximizing my effect size. Then, I could advertise my product as being "clinically-proven".
The author's of this study concluded that:
"these data indicate that PUA ameliorates experimental IBD by down-modulating inflammation in mucosal immune and epithelial cells"
In reality, all that this study demonstrates is that, in this mouse model fed this background diet, providing 14% of the fat as punicic acid reduces certain inflammatory markers / outcomes compared to providing 14% of fat as linoleic acid. Unfortunately, no where in the results or discussion do the authors acknowledge the pro-inflammatory effects of linoleic acid - perhaps they assume that the readers are aware of this fact.
This study was funded by Lipid Nutrition, a company that produces and sell fatty acid supplements. Moreover, the primary author has filed a patent related to punicic acid. Although this information was provided (in small print at the end of the paper), given the obvious conflicts of interest, I doubt that objectivity could be maintained here - perhaps explaining the limitations discussed. Negative results would have been very hard to publish.
Why was this experiment conducted in the first place? It is possible that punicic acid is just a really promising fat, and that the good people at Lipid Nutrition believe that it may be useful for disease treatment and/or prevention. However, at the risk of sounding cynical, I think that the real reason is far less scientific and selfless. Pomegranates have recently become recognized as a "super food" thanks to their high anti-oxidant levels. I feel that it has gotten to a point where I could add a few drops of pomegranate juice to iced tea, and sell it for a dollar more as a health drink.
While we are on the topic, there are no "super foods" - it's a genuinely stupid idea that people really need to get out of their minds. All real foods are super, and with adequate funding and time, I am confident that researchers could extract hundreds of different nutrients from any real food, and design a study that would demonstrate some health-enhancing property. I use the term real food intentionally to differentiate it from the other edible foodstuff that can be purchased at the supermarket.
Back to the matter at hand. The pomegranate juice and the seeds are kind of a package deal, so as the demand for juice increases, there is going to be a surplus of cheap seeds. This creates an opportunity for companies that are able to find a use for them. Turning them into expensive fatty acid supplements is almost poetic, and I would commend their efforts if they weren't so unnecessary and underhanded. The consumers that buy pomegranate juice for its anti-oxidants are likely the same ones that would purchase punicic acid supplements for its anti-inflammatory properties. If only there were a single product that had it all for less.
It is not surprising that the formation of juice would result in the loss of important nutrients, and lends further support to the notion that you should not drink your fruits and vegetables. Although I must admit that it is far more profitable for food manufacturers to sell plants in their individual bioactive components, I'm not convinced that this is in any way better for the otherwise healthy consumer. As for nutrition as a science, I imagine that it will continue to go where the money is, providing the evidence required to create the demand needed by the food industry.
Bassaganya-Riera J, DiGuardo M, Climent M, et al. Activation of PPARg and d by dietary punicic acid ameliorates intestinal inflammation in mice. Br J Nutr 2011; 106: 878-86.
