CLnA, the "Omega-3 Variety" of CLA from Pomegranate & Co, Has Potent Anti-Obesity Effects and the Potential to Become More Than Just Another Anti-Diabetes Drug.

Image 1: Pomegranate - I loved to eat them even before I realized that their seeds are the #1 dietary source (83%) of punic acid.

While more and more people are beginning to grasp the notion that with (naturally occurring) fats - as with everything else in life - there is no simple "good" and "bad", no clearcut "black" and "white" and no definite "beneficial" and "detrimental". The number of different fatty acids and their respective effects on the human metabolism is so vast that it is pretty hard to keep track of all those varieties of saturated and unsaturated carboxylic acids. I would thusly not be surprised if you simply assumed that the "n" in the headline of this blogpost was a type that had slipped in because poor Dr.Andro is chronically stressed from Christmas shopping... well, while the latter is actually correct, the former is not: CLnA is actually the omega-3 variety of the famous conjugated linoic acid (CLA), which in and out of itself is not a single but a group of 28 different trans- and cis-isomers that occur in our diet mainly in the shape of high and full-fat meat and dairy products.

CLnA - Conjugated Linolenic Acid is not a typo ;-)

Within the last couple of years even the medical establishment has come to realize that the chronic omega-6 (n6: linolic acid) overload in our diet is killing us. The "heart-healthy" PUFAs have now become the more and less heart-healthy PUFAs with the totally healthy *rofl* omega-3s and the not just as healthy omega-6s - both, of course, still totally "essential" and WAY better than saturated fats,... (attention: the afore statements are full or irony! Saturated fats are of course NOT the bad guys. Sorry, David if that lead to confusion)... but I am getting derailed, here. So let's get to the point. What every reasonable person appears to agree on, these days, is that we have to lower the ratio of n6:n3 fatty acids in our diets. Now, I am asking you: Has it ever occured to you that CLA essentially is an omega-6 fatty acid? I mean its conjugated linoleic acid - "linoleic" as in omega 6 = linoleic acid! Probably not, right? The reason for that is yet (hopefully ;-) not that you are dump, but simply that the existence of an omega-3 "variety of CLA", namely conjugated linolenic acid, or short, CLnA, is something about which you will only hear, when you read blogs (such as the SuppVersity ;-), which do not stick to copying, pasting and commenting the stuff the authors have read on one of the major news-portals.

Table 1: CLnA isomer content in natural sources (data adapted from Hennesey. 2011)

From a molecular perspective,  CLnA isomers combine the conjugated double bond system of the classic conjugated linolic acid, you know, with the octadecatrienoic fatty acid (C18:3) structure of omega-3s, i.e. linolenic acid. Interestingly, this make-up confers these fatty acids with a high bio-active potential. Now, while this may sound like one of the frankenfood test-tube results of the gene-technology laboratories of Monsanto, we know at least 10 CLnA isomers which occur naturally in foodstuff or as byproduct of fermention processes (cf. table 1).

Adiposity, hyperlipidemia, cancer - CLnAs could help with all!

Image 2: Even if CLnAs would just prevent obesity, this illustration I borrowed from multiplemyelomalifeexpectancy.tk, shows that not being / getting obese alone would prevent a plethora of related maladies. Such as kidney failure, arthritis, gallbladder disease, infertility, asthma, fatty liver disease, sleep apnoea, depression, heart disease, hyperlipidemia, diabetes,... basically every major ailment the increasingly obese convenience society of the Western hemisphere is suffering from.

Due to their anti-adipogenic (meaning preventing the accumulation of body fat) effects CLnA fatty acids have been investigated as potential candidates for the treatment of the obesity epidemic for quite some time, now (Hennesey. 2011). In a 2002 article that was published in the Journal of Applied Biochemistry and Biotechnology, Nishimura et al. report that CLnA isomers exert apoptotic effects on mouse preadipocyte 3T3-L1 cell - or, in plain English, incubation with CLnA did not only hinder the "pubertal" fat cells from becoming mature adipocytes, it actually killed them. In vivo studies with rodents, such as Arao et al. (2004), where the administration of a diet that was enriched with 1% pomegrenate seed oil lead to a 27% reductin in omental white adipose tissue, were able to confirm the "rodent-real world signficance" of these test-tube results.

Other studies showed a normalization of hyperlipidemia in rodent models of the metabolic syndrome and a hand full of studies have explored the usage of CLnA isomers as cytotoxins in the treatment of cancer. In their concise review of the literature, Hennesey, et al. thusly rightly conclude that with their "potent inflammatory and immune modulating properties", their ability to "reduce the risk of obesity, improve cardiovascular health, and mediate strong anti-carcinogenic activity", the use of CLnA isomers or dietary enrichments could offer treatment strategies for pathologies, which "represent some of the greatest mortality risks to humans in the Western world and have been inextricably linked with diet" (Hennesey. 2011).

Adding diabetes to the list of potential targets for CLnA

For today, we are however going to focus on the most recent result from the research front: The effects of CLnAs on diabetes, or, to be precise, the increases in blood glucose, and decreases in anti-oxidant capacity that go hand in hand with the latter. In a recently published study (Saha. 2011), Siddhartha S. Saha and Mahua Ghosh from the Department of Chemical Technology at the University College of Science and Technology of the University of Calcutta (I don't have to tell you that this is in India, do I?) injected male albino lab rats with 60mg/kg streptozotocin (STZ) - this is a common and well-established method to induce a metabolic state that serves as a model of type II diabetes - and fed them diets that contained either no, or 0.5% of the total fat in the form of alpha-eleostearic acid (from bitter gourd, cf. table 1) or punic acid (which was in this case taken from snake gourd oil, but could as well have been extracted from the eponymous pomegrenate, cf. table 1).

Figure 1: Relative blood glucose levels vs. non-STZ injected control in streptozotocin injected rats over the course of the dietary intervention (data calculated based on Saha. 2011)

As you can see in figure 1, this 100% natural "food additive" had a more than pronounced effect on the +300% (vs. non STZ-injected control) elevated blood glucose levels of the "type-2 diabetic" rodents.

Figure 2: Relative level of lipid peroxidation (left) and total antioxidant capacity (right) levels vs. non-STZ injected control in streptozotocin injected rats after the 28-day dietary intervention (data calculated based on Saha. 2011)

And while the glucose levels were still 150% above those of the healthy control levels, the streptozotocin-induced lipid peroxidation in plasma, pancreas and erythrocytes of the lab animals was ameliorated by the snake gourd oil treatment (remember that is the stuff from pomegranate) and even reversed by the bitter gourd diet. Judged by the standardized FRAP assay, the "diabetic animals" that were fed a diet that contained 0.1% alpha-eleostearic acid (of the total diet, which had 20% fat) even exhibited a 10% greater total antioxidant capacity than the totally healthy control!

Figure 3: Relative expression of inflammatory cytokines, TNF-alpha and interleukin 6 in plasma capacity (right) levels vs. non-STZ injected control in streptozotocin injected rats after the 28-day dietary intervention (data calculated based on Saha. 2011)

Snake gourd oil, on the other hand, exhibited more profound effects on the elevated TNF-alpha, interleukin-6 and NF-kappaB levels of the STZ-treated rodents (cf. figure 2) and thus, at least this is my humble opinion, render punic acid the overall more promising agent with respect to the treatment of all sorts of inflammatory (or related diseases). After all, disturbances in the regulation of the nuclear factor kappa-light-chain-enhancer of activated B cells  (NF-kappaB) and the downstream over-expression of TNF-alpha and IL-6 are hallmark features of allmost all the aforementioned ailments of the increasingly obese western convenience society. This is also why I am quite certain that we are going to hear much more about the CLnAs in the month to come... and I guess, I don't have to tell you that right here, at the SuppVersity, is where you will read about respective studies first!