Conjugated Linoleic Acids: What's the Difference Between cis-9,11 and trans-10,12 CLA and Should We Label Them as "Transfats"? Plus: What Makes CLA Potentially Harmful?

If Hayden Panettiere drinks it dairy can't be bad - despite (or because?) CLA, right? Well, what if I told you that Mrs. Panettiere was advertising milk in the "Got Milk" campaign despite being lactose intolerant?

As a SuppVersity veteran you will be familiar with the idea that trans-10, trans-12 conjugated linoleic acid is the "fat burning" CLA isomer, while 9 cis,11 trans linoleic acid appears to blunt some of the pro-inflammatory actions of its cousin and has been shown to have specific physiological effects on it's own (e.g. increased bone health, cf. Platt. 2009; anti-cancer, cf. Corl. 2003).

As I already mentioned, this is probably nothing new for you, if you make sure to get your daily dose of SuppVersity wisdom everyday. What you may however not be aware of is the fact that researchers like Ye Wang and Spencer D. Proctor are - despite the never-ending hoopla around potential weight loss effects of CLA - still contemplating, whether CLA could not pose a major health threat to all or at least certain subgroups of the population and whether this should or shouldn't be reason enough to change the current food labeling practices.

Do we have to label CLA as "transfat"?

From a technical perspective the above question is obsolete. CLAs are transfats and would thus (technically, again) have to be labeled as such on the product label. From a health perspective, however, things do in fact look different. Due to the fact that the aforementioned ruminant (=naturally produced in the stomach(s) of ruminents) trans-fats have been associated with health benefits (Gebauer. 2011), we could effectively risk to scare consumers away from healthy foods if they were listed as part of the "transfat" category on the product labels.

What's actually the reason that one the same CLA isomer that will have you lose body fat will also "inflame" you? Due to the fact that most of the research on "fat loss supplements" is conducted in sick, obese individuals, people tend to get the false impression that "fat burners" were anti-inflammatory and that anti-inflammatory agents would burn fat.

Effects of 10-trans,12 CLA on fatty acids & glucose metabolism and IL-6 gene expression in isolated fat cells in the petri dish (Hartwig. 2013)

Now, while it is correct that soothing inflammation will help the future Mr. Average Joe, who is going to be an obese (pre-)diabetic, lose weight, this has little to do with any active contribution to the oxidation of body fat. 10-trans,12 CLA, on the other hand, has been shown to block lipid storage, increase mitochondrial uncoupling (UCP-2), lower PPAR-alpha and ramp up the oxidation and release of fatty acids from the fat stores (Hartig. 2013). Unfortunately it will also block the uptake of glucose and increase the expression of the pro-inflammatory cytokine IL-6 in fat cells. So, if you took 10-trans,12 CLA at very high doses it will probably in fact keep you lean.

If you cannot handle the sudden increase in free fatty acids, pack the glucose into your liver and muscle glycogen stores and deal with the exuberant amount of inflammatory cytokines, however, it will only make you sick.

Currently, the trans-fat content on many food labels (and in legislative documents) does not include ruminant CLA isomers and Wang and Procter acknowledge that:

"As highlighted in a recent quantitative review of prospective cohort studies by Bendsen et al. dietary consumption of ruminanttrans-fat may be protective against total as well as fatal CHD events." (Wang. 2013)

The researchers do however point out that concerns about potential adverse effect on atherogenic cholesterol profiles from supplemental CLA are not unwarranted - at least if they are used by a group of persons - abdominally obese and/or insulin resistant men, for example (Riserus. 2002 a,b).

Australia and New Zealand suggest a re-evaluation

Accordingly, Australia and New Zealand (FSANZ) proposed to re-evaluate their perception regarding the exclusion of CLA from the TFA definition on nutrition labels.

If you re-evaluate something, you do not necessarily have to change them and if you go through the concise summary of results Wang and Procter present in their paper (see table 1 for an overview of the currently published meta-analyses, it does not appear necessary to question the current practice to label only industrually produced trans fats.

Table 1: Meta analysis with beneficial (green), neutral (grey) and potentially negative outcome (red); based on Wang & Proctor (2013)

As the authors point out, the inclusion of CLA in the total amount of transfats on the label would only drive people away from the consumption of whole food products. This is particularly true in view of the fact that the ill-health effects of "trans-fats" are something everyone will have heard about. The fact that these ill health effects are not to be expected from trans fats in dairy and other CLA containing whole foods, on the other hand, is still news to many costumers.

Moreover, how would you, me and everyone else who may well be aware that CLAs are not the bad guys and the "trans-fat" in grass fat butter is not going to hurt us know if the 3g of transfats in another product we buy are actually from the undisclosed amount of butter (and thus CLA) in it? It could likewise be that the producer added a little extra partially hydrogenated vegetable oil to cut the product costs and neither you nor me would know that.

Suggested read: "A Higher Intake of CLA and Vaccenic Acid from Dairy, Beef, Veal and Lamp Could Prevent Subtle Weight Gain" | read more

Only the obese have to be worried: Based on the currently available evidence the healthy and lean person (hopefully you) has absolutely no reason to avoid products with a "high" natural CLA content and thus both the pro- (trans-10,12) and (partly) anti-inflammatory (cis-9,11) form of CLA in them.

For obese and insulin resistant individuals things do however look somewhat different. A 2004 study by Risérus et al., for example, has been able to show that even the allegedly "harmless", 9 cis,11 trans linoleic acid can worsen both lipid peroxidation and insulin resistance in 25 abdominally obese men. (Risérus. 2004).

With 3g/day the dosage that was used in the Risérus study, the amount of CLA was yet much hither than the amount of CLA you can possibly ingest with nourishing foods such as butter, full-fat dairy, grass-fed beef (and beef in general, by the way). Instead of these you are thus better advised to avoid CLA supplements... but don't worry if you take another look at the data in table 1 you will have to concede that they are pretty much useless, anyway.

Reference:

• Corl BA, Barbano DM, Bauman DE, Ip C. cis-9, trans-11 CLA derived endogenously from trans-11 18:1 reduces cancer risk in rats. J Nutr. 2003 Sep;133(9):2893-900.
• Gebauer SK, Chardigny JM, Jakobsen MU, et al. Effects of ruminanttrans fatty acids on cardiovascular disease and cancer: a comprehensive review of epidemiological, clinical, and mechanistic studies.Adv Nutr. 2011; 2, 332 – 354.
• den Hartigh LJ, Han CY, Wang S, Omer M, Chait A. 10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species. J Lipid Res. 2013 Nov;54(11):2964-2978. 
• Lenz TL & Hamilton WR. Supplemental products used for weight loss. J Am Pharm Assoc. 2004; 44,  59– 67, quiz 67– 58.
• Onakpoya IJ, Posadzki PP, Watson LK, Davies LA, Ernst E. The efficacy of long-term conjugated linoleic acid (CLA) supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials. Eur J Nutr. 2012 Mar;51(2):127-34.
• Platt I, El-Sohemy A. Effects of 9cis,11trans and 10trans,12cis CLA on osteoclast formation and activity from human CD14+ monocytes. Lipids Health Dis. 2009 Apr 29;8:15.
• Risérus U, Arner P, Brismar K, Vessby B. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care. 2002 Sep;25(9):1516-21.
• Risérus U, Basu S, Jovinge S, Fredrikson GN, Arnlöv J, Vessby B. Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance. Circulation. 2002 Oct 8;106(15):1925-9
• Salas-Salvadó J, Márquez-Sandoval F, Bulló M. Conjugated linoleic acid intake in humans: a systematic review focusing on its effect on body composition, glucose, and lipid metabolism. Crit Rev Food Sci Nutr. 2006;46(6):479-88. Review.
• Schoeller DA, Watras AC, Whigham LD. A meta-analysis of the effects of conjugated linoleic acid on fat-free mass in humans. Appl Physiol Nutr Metab. 2009 Oct;34(5):975-8.
• Tricon S, Yaqoob P. Conjugated linoleic acid and human health: a critical evaluation of the evidence. Curr Opin Clin Nutr Metab Care. 2006 Mar;9(2):105-10. Review.
• Whigham LD, Watras AC, Schoeller DA. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Am J Clin Nutr. 2007 May;85(5):1203-11.

Vitamin D3 a "Fat Synthesizer"!? Rodent Study Shows +33% Increased Fat Deposition in Vitamin D3 Supplemented Mice.

Illustration 1: Experts will recognize from looking at these Oil Red O-stained longissimus dorsi slices of mice on a normal and a vitamin D3 supplemented diet that supplemental (! not vitamin D from the sun !) "vitamin D3 can be used a s a fat synthesizer and meat tenderizer in meat-producing animals". (img in illustraton from Choi. 2011)

I have been railing against the current vitamin D hype for months now. In that, I have at no point in time implied that "backfilling" depleted vitamin D levels via supplementation could not be beneficial (or at least not harmful), nor have I at any time excluded that vitamin D3 supplementation (even if you are in the "normal" range) could have its merit (cf. vitamin D3 + HMB). What I have done though, was to point at the lack of controlled studies that would support any of the benefits supplemental vitamin D3 is currently hailed for all over the Internet. This amazes me, because the very same "gurus" who are all over the vitamin D bandwagon have lately (just like me) discarded the data from the Iowa Women's Health Study as "unrealiable" and "non-significant" epidemiological bullshit (which is exactly, what I think, as well). When it comes to vitamin D, however, they throw all their concerns on the validity of epidemiological data over board and worship their vitamin D3 pills like a golden calf.

But let's get to the facts, before I get tarred and feathered, again... In the latest issue of the Journal of the Science of Food and Agriculture Hyuck, Choi and Kyuho Myung published a paper that investigated the use of vitamin D3 supplements to fatten animals (Choi. 2011). Now, you may think "How stupid is that, everyone knows that vitamin D will make you lean out!", but as I've pointed out several times within the last weeks, high vitamin D levels may correlate with a lean body composition; however, studies that would show that supplementation of the latter would induce respective changes in body composition in the absence of prior deficiency (and we are talking about the standard reference range with a lower limit of 10ng/mL, here) simply do not exist... but I am digressing again.

Figure 1: Composition of the diet (large figure) and respective vitamin D3 content (small figure) of the diets of the control and the supplement group in the study.

As you can see in figure 1 both groups (2x N=10) of 6 weeks-old male C57BL/6 mice were fed identical chows (AIN93G; cf. figure 1, large), varying only in their vitamin D3 content (1IU in the control group, 10IU in the supplemented group). In human terms this would be like switching from your common western low vitamin D diet with roughly 800IU to taking a 8.000 IU supplement, each day - something I suppose many of you may have done lately!?

Figure 2: Body fat (in g; large figure) and respective serum 1α,25-(OH)2 -vitamin D3 levels (in µg/mL; small figure) after 3 weeks on control or vitamin D3 supplemented diet (data calculated based on Choi. 2011)

As figure 2 shows, this 10-fold increase in dietary vitamin D would only be advisable if you were a "sumo mouse" who has to make weight for the next competition. A plus of +33% in total, +29% in unaesthetic subcutaneous and +25% in unhealthy visceral fat (all statistically significant with p<0.022, p<0.032 and p<0.043) is not what you would expect of the "greatest vitamin of all time" - would you? And while the vitamin D3 mice also gained some more body weight, those changes were statistically non-significant, so that - as the scientists state - vitamin D3 turned out to be an ideal "fat synthesizer and meat tenderizer".

Figure 3: Cytokines, UCP-2 and PPAR-gamma expression in mice after 3 weeks on control or vitamin D3 supplemented diet (based on Choi. 2011)

In that, vitamin D3 works it "fat synthesizing" magic by increasing the inflammatory cytokines TNF-alpha and IL-6 and decreasing the muscle anabolic (Busquets. 2005) and fat catabolic cytokine IL-15 (Carbo. 2001; Alvarez. 2002), as well as the uncoupling protein UCP-2 while ramping up fat storage via increase PPAR-gamma expression (cf. figure 3).

Now obviously, this is just another rodent study and we cannot say how and if the results will translate to humans, but it is a controlled study and it investigates the effects of supplemental vitamin D3 which is something you cannot say of the "scientific backbone" of the current vitamin D3 craze... and now tar and feather me like a child who has just been bereaved of his favorite toy, if you will ;-)