Docosahexaenoic Acid (DHA) Blunts Negative Side Effects of Conjugated Linoleic Acid (CLA) W/out Hampering Its Effects on Body Fat Loss & the Expression of Obesity Genes

She already knew what scientists have recently discovered and now confirmed: You better stack CLA and DHA if you want lean and health offspring ;-)

Conjugated linoleic acid (CLA) is not only an omega-6 fatty acid, it's also a trans-fat (though a natural one) and still even scientists believe that it could contribute to the solution of the diabesity epidemic, if it (a) finally yielded the same extreme fat loss (yep, just the blubber, nothing else) results in human beings as in rodents (cf. "CLA Annihilates Body Fat and Increases Endurance") and (b) anywhere near appropriate doses would not hold he risk of inducing fatty liver disease and insulin resistance (Clément. 2002). At least with respect to (b) a "bodybuilding approach" to CLA supplementation which is based on the "if hammering your head against the wall hurts, you better make sure you wear a helmet" principle of stacking CLA and PUFAs, esp. the long-chain omega-3 fatty acid DHA, has already yielded some promising results in a study that has been published earlier this year (Fedor. 2012a).

Since, the deposition of fat in the liver in response to CLA supplementation is in the end only the logical consequence of CLA's lipolytic (=fat releasing) and anti-lipogenic (=inhibition of fat storage) effects in the adipose tissue, the absence of adequate data on the amount of fat in adipose tissue and muscle or the fatty acid composition of liver, adipose tissue, and muscle, nor did we monitor the changes in the expression of genes involved in fatty acid metabolism in adipose tissue and muscle in the respective study did not allow for the conclusion that the co-supplementation of DHA would not blunt the beneficial fat loss effects of CLA, as well.

Is it possible that high dose DHA blunts the negative and the positive effects of CLA?

In a paper that's going to be published in the next issue of Metabolic Syndrome And Related Disorders Dawn M. Fedor et al. describe the results of a follow up study, which dealt with this very question and I guess I am not giving away more than what you will already inferred from the headline of this post, when I tell you that the answer to the question in the subheading is "No, DHA does not blunt the beneficial effects of conjugated linoleic acid on adipose tissue!"

Figure 1: Relative body weight, liver weight, periuterine fat mass, muscle weigh, liver total lipid weight, adipose total lipid weight, and muscle total lipid content of the mice after 4 weeks on a 0.5% CLA, 0.5% CLA + 1.5% DHA or 1.5% DHA diets expressed relative to respective data from mice on the standard chow (Fedor. 2012b)

If you take a closer look at the data in figure 1 you will realize that the provision of a diet that contained 0.5% CLA (only the "active", but potentially hazardous t10, c12 isomer was used in the study) and 1.5% DHA did not blunt the beneficial effects on total and periuterine body fat mass in eight-week-old, pathogen-free female C57BL/6N mice. On the other hand, it did mitigate the negative effects on liver weight and (and this is actually quite remarkable) had identical beneficial effects on liver fat as the DHA only diet.

DHA + CLA = perfect synergists

Although the "equation" above may sound as if I had taken it right from one of those shiny adds in a muscle mags, it does in fact look, as if the combination of CLA + DHA was the silver bullet for healthy body fat (and I repeat only body fat not lean mass!) reductions in the absence of any dietary and/or exercise interventions.

Figure 2: Expression of selected genes involved in the synthesis, storage and release of fatty acids from the adipose tissue; the respective values (in a.u.) of the control group were all 100, so you can thing of these as percentages, as well (Fedor. 2012)

Moreover, the analyses of the expression of pro- and anti-obesity genes in the adipose tissue does actually support this claim:

"CLA significantly decreased the expression of LXRb, PGC1a, PPARg, SREBP1C, ACOX1, and CD36 adipose mRNA when compared to the control group. We also observed a trend for CLA to decrease the expression of HSL (P=0.08). DHA was not able to prevent any of these decreases in gene expression. CLA significantly increased UCP2 mRNA expression when compared to control group; DHA again had no effect." (Fedor. 2012b)

If we translate all these acronyms the scientists use to describe the data I've plotted for you in figure 2 into plain cause and effect relations, we could simply state: CLA induced changes in the expression of genes in the adipose tissue of the rodents that would prevent the maturation of adipocytes and the synthesis and accumulation of fatty acids, while increasing their release into circulation,  and DHA did not effect these changes.

DHA takes care of the energy that's released / not stored in fat cells

What the co-administration of DHA did, however, was to prevent the deposition of the energy that was released, respectively not even stored in the adipocytes in the liver -- and it did that so effectively that the overall weight of the liver of the mice in the CLA + DHA group was not greater than the the liver weight of the rodents in the control group.

Figure 3: Liver fatty acid composition (µmol/g) and omega-3 : omega-6 ratio after 4 weeks on regular (control), 0.5% CLA, 0.5% CLA + 1.5% DHA and 1.5% DHA diets (Fedor. 2012b)

In fact, the co-administration of conjugated linoleic acid and DHA did even reduce the total fatty acid content of the liver (not to a statistically significant degree, though) and brought about profound changes in its fatty acid content - most prominently, a whopping +975% increase in the omega-3 : omega-6 ratio (see small graph in figure 3) that were even slightly more pronounced in the CLA + DHA group than in the DHA only group (you do remember that CLA is an omega-6 trans-fat, right?).

Finally a stack that works -- but will it work in humans, as well? 

I don't know if it dawned on you, already, but dairy and butter from grass cows already has both CLA and DHA in it - what a lucky coincidence, isn't it? Still, there is one downside: You simply cannot eat enough of it to get anywhere close to the human equivalents of the amounts that are used in rodent studies.

Now, although both the changes in body fat levels in the CLA + DHA group were consistent with those observed in the CLA only group and the effects of the combination treatment on the changes in hepatic fatty acid composition were consistent with those observed in the DHA only group, there is still one question we have to answer: Are we going to see similar esults in humans?

To be honest, I still cannot answer this question, but if you take into consideration that no previous human trial used dosages in the 20-30g range simply because that would be unethical given the associated side effects, we may soon get an answer to this question - as soon as scientists dare to slowly escalate the dosage, trusting on the ability of supplemental DHA to blunt the negative, while conserving the beneficial effects of CLA.


References:

• Clément L, Poirier H, Niot I, Bocher V, Guerre-Millo M, Krief S, Staels B, Besnard P. Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J Lipid Res. 2002 Sep;43(9):1400-9.
• Fedor DM, Adkins Y, Mackey BE, et al. Docosahexaenoic Acid prevents trans-10, cis-12-conjugated linoleic Acid-induced nonalcoholic Fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation.Metab Syndr Relat Disord. 2012a;10:175–180
• Fedor DM, Adkins Y, Newman JW, Mackey BE, Kelley DS. The Effect of Docosahexaenoic Acid on t10, c12-Conjugated Linoleic Acid-Induced Changes in Fatty Acid Composition of Mouse Liver, Adipose, and Muscle. Metab Syndr Relat Disord. 2012b Nov 21.

4g of Conjugated Linoleic Acid Promote CYP17A1 + Leydig Cell Testosterone Production and Increase Cardio-Mediated Muscle, Strength and Endurance Gains

"That's all the exercise in induced T-response, bro. Now shut up, I got to squat!"

Yes, this is another of those rodent studies of which we simply don't know if the results will eventually translate to humans. In contrast to previous studies on CLA, which dealt with weight loss and produced marvelous results (see "CLA Destroys Body Fat & Increases Endurance!" | read more) which could not be reproduced in human trials.

This very recent paper from Italy deals with CLA's effects on exercise, testosterone, and potential gains in muscle mass and leaves the parameter body fat out of the equation (Barone. 2013).

"Hold on, that's not news, is it?"

When Roy Nelson shot me the link to the pertinent paper by Rosario Barone et al. (2013), the above, i.e. "Hold on, that's not news, is it?" was actually my first thought. After all, I had written about the purported muscle building effects of CLA in the past (see "Review Claims: CLA & Fish Oil Improve "Anabolic" Effects of Exercise - What Does the SuppVersity Sniff Test Say?" | read more). After briefly checking my previous article, I did realize, though: This is news!

The previous article did not discuss the same results. It did however come from the same team of Italian researches and made the claim that CLA & fish oil would be natural anabolics (read it!) - a claim I reviewed and wrote:

"[...] as far as ergogenic and/or anabolic effects are concerned, CLA is unquestionably the more promising fatty acid off the "two" (actually we are talking about four fatty acids, here: DHA + EPA = fish oil and cis-9,trans-11 and trans-10,cis-12 CLA)." (SuppVersity. 2013)

I have to admit, though, that I was thinking of CLA's ability to block the storage of body fat on a bulk, primarily - not so much about its not yet fully, but at least half-way established effects on exercise performance. The testosterone boosting effects, on the other hand, were something I discarded, so that it's about time to look at them more closely.

In vitro + in vivo - that's the way Barone et al. did it

In a first attempt to access the effects of CLA on the testicular androgen production, the scientists from the University and Hospital of Palermo conducted a couple of tests in the petri dish. Usually boring stuff, if it were not for geeks like me (and some of you) who always ask the nasty question: "Why".

Figure 1: The same research group published a paper that showed increased testosterone in young men on a resistance training regimen. It is therefore not totally unlikely that the results do translate to human beings; the figure shows the total testosterone before vs. after a workout in ng/dl (Macaluso. 2012)

In this case, we are lucky, because Barone et al. did not focus solely on the amount of steroids the the leydig tumour cells (don't worry that should work with regular cells, as well) were spilling out. They also tested for enzymatic changes and observed that as 17α-hydroxylase/17,20-lyase (CYP17A1), which converts progesterone into androstenedione and has  been demonstrated to have direct downstream effects on the testosterone production (Svechnikov. 2009; Weisser. 2011).

As every SuppVersity reader knows, the cytochrome P450 enzyme cascade is on of the most powerful and overlooked actors in the steroid orchestrate. While CYP17A1, which does effectively increase the production of testosterone pre-cursors and will thus exert an indirect beneficial effect on the testosterone production, other members of the cytochrome family facilitate the conversion and clearance of testosterone.

Against that background it was sound to expect to observe similar effects in the in-vivo part of the study. The interplay with other enzymes, however, could easily have thwarted the results. Outside of the petri dish the sheer number of variables that could change the outcome of the study makes it more or less impossible to predict the "exact" study outcome and - I want to emphasize this - the latter could well look slightly or completely different from what you see in Figure 2, when you went ahead and tried to support your training efforts with 4g of the patented Tonalin® FFA 80:

Figure 2: Free testosterone and CYP17A1 expression in the supplemented (CLA-) /  unsupplemented (PLA-) mice after 6 weeks of no (SED) or 15-60min (ramp up) of exercise 5x per week (Barone. 2013).

I hope you did notice the important hint I hid in the last sentence above Figure 2, where it says: "Support your training efforts..." If you didn't take a look at Figure 2 ... I guess, it's obvious to see that this short insert is of paramount importance: No training, no CLA bonus!

"The protein expression of CYP17A1 was significantly higher in both the trained groups (PLA-TR and CLA-TR) compared to the sedentary groups (PLA-SED and CLA-SED) (P <0.01). Moreover, CLA supplementation induced a further increase in CYP17A1 protein in the CLA-TR group compared to the PLA-TR group (P < 0.01)" (Barone. 2013)

In other words, training alone is a CYP17A1 powered testosterone booster and CLA is an adjuvant, which has no effect in the absence of 6 weeks with five "cardio" sessions/week at an ever-increasing pace and duration (15-60min and 3.2-4.8m/min from week 1-6).

Figure 4: Body weight gain, and force/body weight gain  (in %; top) and distance traveled relative to SED-PLA group (Barone. 2013)

"Wow that's exciting, isn't it?" Actually no - not really. The increase in testosterone alone would hardly be worth the paper this article is probably never going to be printed on. What is at least borderline exciting, though, are the increase in muscle gains, strength and running distance the rodents covered in a standardized test (see Figure 3).

Yeah, I have to admit: The data does look exciting, but that can be said of the previously referenced study by Macaluso, as well. The said human trial (see Figure 1), however, tells us that it's probably unrealistic to expect similarly pronounced effects with even more CLA (6g in the Macaluso study from 2012) in men.

Personally, I would save the money, but if you want to try it: Go ahead... and tell us if it works ;-)

I, for my part, am missing anecdotal evidence (You can't tell me that there is no one who has tried that already - so where are the "CLA is king, bro!" posts on the various boards?), the confirmation of this or at least similar effects by other scientists and a 'Conflict of Interest' declaration at the end of a paper that puts such an emphasis on the "®" in  Tonalin® FFA 80.

References:

• Barone, R, Macaluso F, Catanese P, Marino Gammazza A, Rizzuto L, et al. Endurance Exercise and Conjugated Linoleic Acid (CLA) Supplementation Up-Regulate CYP17A1 and Stimulate Testosterone Biosynthesis.  PLoS ONE 8(11): e79686.
• Macaluso F, Morici G, Catanese P, Ardizzone NM, Marino Gammazza A, Bonsignore G, Lo Giudice G, Stampone T, Barone R, Farina F, Di Felice V. Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo after an acute bout of resistance exercise. J Strength Cond Res. 2012 Jun;26(6):1667-74.
• Svechnikov K, Spatafora C, Svechnikova I, Tringali C, Söder O. Effects of resveratrol analogs on steroidogenesis and mitochondrial function in rat Leydig cells in vitro. J Appl Toxicol. 2009 Nov;29(8):673-80.
• Weisser J, Landreh L, Söder O, Svechnikov K. Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells. Mol Cell Endocrinol. 2011 Jul 20;341(1-2):18-24. doi: 10.1016/j.mce.2011.03.008.

A Higher Intake of CLA and Vaccenic Acid from Dairy, Beef, Veal and Lamp Could Prevent Subtle Weight Gain in Healthy Middle-Aged Individuals. Is 1.5g/day the Magic Number?

A dairy cow: Does her stomach hold the key to a leaner, healthier life or are CLA and vaccenic acid, the ruminant trans-fatty acids just as bad as their grainy cousins?

There are supplements that work and supplements that don't work and then there are those supplements, where nobody can actually tell, whether they belong to the former or the latter category. Conjugated linoleic acid, the ruminant omega-6 trans-fat you will find at particularly high concentrations in milk and meat products from grassfed dairy, unquestionably belongs to the latter category. While we do actually have plenty of in parts almost unsettlingly impressive rodent data (e.g. "CLA Destroys Body Fat & Increases Endurance! But at Which Costs?"), the outcomes of independent  controlled human studies are equivocal; with results ranging from "total failure", to "promising, but not half as impressive as we have expected based on previous rodent studies".

That being said, I was quite intrigued, when I hit onto a recently published study that takes a novel angle on the whole CLA for weight loss issue. One I usually don't like, as it involves a lot of statistical shenanigan, but still appears appropriate in this particular case, where the controlled small scale trials are failing us.

The Nordic Men (and women) love their full-fat dairy - rightly so?

If you are a loyal reader of the SuppVersity, who does not just read the detailed elaborations here on www.suppversity.com, but is also following the latest short news on the SuppVersity Facebook Wall, it probably won't surprise you that the study which is going to be published in the October issue of the European Journal of Clinical Nutrition has been conducted in Northern Europe. After all, you will have noticed that many of the interesting short news items relating to (larger scale) studies on the effects of one or another of the "bad fats" are conducted at universities and research centers in Sweden, Finland, Norway and, as in this case, Denmark - at the Aarhus University, to be precise, where Hansen and his colleagues datasets from the Diet, Cancer and Health study from December 1993 to May 1997. The participants, 160,725 men and women, aged 50–64 years, who were all born in Denmark and had been living in the greater Aarhus or Copenhagen areas, had all completed detailed food frequency questionnaire (FFQ) and a self-administered lifestyle questionnaire, before they underwent a physical examination and a follow up 5-6 years later.

How did the scientists know how much CLA and vaccinic acid the individual food items contained? unfortunately, they didn't. The way by which they calculated / estimated it,  i.e, by combining the content of r-TFAs in milk fat (data based on another Danish study) with the content of milk fat in dairy products given by the Danish food composition tables and using the values of r-TFA content in ruminant meat products representative of the supply in Denmark, does however make sense to me. The resulting averages should therefore be relatively reliable.

Based on the 77 food items of the food frequency questionnaires which contained ruminant trans-fatty acids R-TFA (this includes both CLA, as well as vaccinic acid which can be converted to CLA in the human body; cf. Turpeinen. 2002), i.e.

• dairy products (n=63), 
• ruminant meat products (beef, veal or lamb) (n=2), and
• composite recipes containing both dairy and ruminant meat (n=12) 

Hansen et al. calculated the average r-TFA intake of each of the 57053 subjects with complete datasets and correlated them with the participants changes in body weight and waist circumference (WC) over the 5-year period to the follow-up.

A massive amount of data suggest minimal amounts of r-TFA are necessary

As the subheading to this paragraph already reveals, the result of the all this statistical shenanigan suggest that the ruminant trans-fatty acid intake from foods, not supplements, does have a beneficial effect on the change in total body weight (an ameliorating effect on weight gain, to be precise).

Figure 1: Absolute intake of ruminant R-TFA (in g/day) and changes in weight; adjustment for sex, age, height, baseline weight, smoking, alcohol intake, education, weighted intake of foods containing high amounts of I-TFA (g/day) and in women, menopausal status and hormone replacement therapy (Hansen. 2012).

A brief glance at the graphs in figure 1 will yet also tell you that their effect on body fatness (as indicated by changes in visceral adipose tissue), is negligible, not to say non-existent. In a way you may say that this is a good thing, because the turning point at a daily r-TFA intake of >1.5g/day, where the restricted cubic spline (that's a statistical fit into the data; figure 1, solid lines) seems to indicate that r-TFA intakes of more than 1.5g/day would precipitate weight gain, is thus absent as well.

Figure 2: Relative intake of R-TFA (in % of total energy intake) and changes in waist circumference. Solid lines: restricted cubic spline with five knots; Dashed lines: 95% confidence interval; same adjustments as in figure 1(Hansen. 2012)

In addition, if we do also consider total energy consumption and the contribution of r-TFAs to the latter (see figure 2), it becomes obvious that we cannot neglect the profound widening of the 95% confidence interval in figure 1 (dashed lines), which tells us that some of the high r-TFA consumers did get even leaner, while others did gain a significant amount of weight. Adjusted for caloric intake and the other confounding variables this effect vanishes and a trend towards lower / even no body weight gain in high r-TFA consumers becomes visible (even within the higher intakes, where the confidence interval widens, due to the lower number of participants, but does not change the general trend). The beneficial effect on waist circumference, however, remains negligible.

So what, if anything, can we learn from these results?

At first sight, the results of the study at hand seem to stand in line with what you have read in "Fat Advantage: 61% Lower Rates of Metabolic Syndrome in High Fat Dairy Lovers", here at the SuppVersity exactly one week ago. It even appears to provide a mechanism by which the high fat dairy products could exert their highly desirable anti-obesity effects, if the high CLA + vaccenic acid (r-TFAs) consumers in the Hansen study were not just the subjects who gained the least weight (measured against their nutrient intake and adjusted for all sort of other confounding factors), but also those with the lowest increase in visceral adipose tissue.  

If that were the case, however, the graph on the right hand side of figure 2 should have at least some kind of slope. Since it hasn't, we must assume that the beneficial health effects of r-TFAs are either (a) not brought about by changes in visceral obesity, (b) the latter are not appropriately quantified by simply measuring the waist circumference or (c) in view of the fact that we are not talking about "weight loss", but rather a prevention of the (partly probably age induced) increase in weight gain a stable waist circumference has to be considered a "success", already.

The scale is an unreliable tool to judge visceral obesity. And even a measuring tape can be misleading, if you are really "skinny fat".

Personally, I tend towards a combination of all three. First of all even moderate weight gain has been shown to increase the risk of impeding metabolic syndrome. The weight stability over >5years in the high r-TFA consumers must therefore be considered to be prognostic of a lower risk of metabolic syndrome. Secondly, visceral does not necessarily equal abdominal fat. Especially in older individuals the gynoid fat areas contribute to visceral obesity, as well. Moreover, we all know the skinny fats, men and women with a relatively large amount of highly inflammatory visceral fat and normal or even low waist circumferences also known as "normal weight obese"; cf. Romero-Corral. 2010).

And thirdly and most importantly: Weight loss is mainly an issue for people who are already overweight or obese. For best-agers who are still in form (and in Denmark there are such people ;-), success is better defined by maintaining the muscle mass you have, not accumulating additional (visceral) body fat and leading an overall healthy lifestyle. That ruminant trans-fatty acids can, maybe even should be a part of the dietary side of this healthy life-style is therefore the main take home message of this study.

What should not be forgotten, however, is the fact that this study was at least in parts supported by the Danish Dairy Research Foundation, certainly not an organization with a particular interest in "bad news" on vaccenic acid, conjugated linoleic acid and dairy products in general, right?


References:

• Hansen CP, Berentzen TL, Halkjær J, Tjønneland A, Sørensen TI, Overvad K, Jakobsen MU. Intake of ruminant trans fatty acids and changes in body weight and waist circumference. Eur J Clin Nutr. 2012 Oct;66(10):1104-9. doi: 10.1038/ejcn.2012.87.
• Romero-Corral A, Somers VK, Sierra-Johnson J, Korenfeld Y, Boarin S, Korinek J, Jensen MD, Parati G, Lopez-Jimenez F. Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J. 2010 Mar;31(6):737-46.
• Turpeinen AM, Mutanen M, Aro A, Salminen I, Basu S, Palmquist DL et al. Bioconversion of vaccenic acid to conjugated linoleic acid in humans.Am J Clin Nutr2002;76: 504–510.

CLA for Lean Gains! Trans-10, cis-12 Conjugated Linoleic acid, But Not the Cis-9 Isomer, Decreases De Novo Lipid Synthesis in Human(!) Adipocytes by More Than 50%

Image 1: Most commercially available
products still have a mixture of the active
10,12 CLA and the inactive 9,11 CLA.

If you read the first installment of the SuppVersity Student Spotlight, and/or listened to our now famous SuppVersity student, Duong, on Carl Lenore's Super Human Radio, yesterday, you'll know that Duong's approach to intermittent fasting delivered impressive muscle gains, even on a caloric deficit! But what if you are lean already? Regardless of whether or not you fast intermittently, eating a hypocaloric diet (i.e. eating less calories than you need) does not appear to be the ideal strategy to "bulk", does it? Well, a group of international scientists from Denmark, the US, France and Germany recently found that CLA, or Trans-10, cis-12 Conjugated Linoleic Acid, to be precise, could possibly ward off fat gains by decreasing the amount of fat that is produced and getting stored in your adipose tissue (Obson. 2011).

Thomas Obsen and his colleagues found that incubation of cultured human adipocytes (human fat cells) with 30 μM 10,12 CLA, but not 9,11 CLA (the other of the two most abundant CLA isomers,

decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides [from
[14C]-acetic acid and [14C]-pyruvic acid as substrates] within 3–24 h. [It also] decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h.

With regard to the underlying mechanism, the scientists are quite certain that it was not "due to a 'structural trans effect'", because several other trans FA, the scientists used as controls "did not delipidate adipocytes or alter the MUFA/SFA ratio to the extent of 10,12 CLA".

Figure 1: Relative changes in de novo lipogenesis of triglycerides and free fatty acids in adipocytes incubated with either 9,11 or 10,12 CLA vs. control (data adapted from Obson. 2011)

 As an alternative explanation they propose that the anti-fat effects of CLA may be "due to the position of the trans double bond in the C18:2 structure of CLA." This would also be consistent with the experimental data (cf. figure 2), which shows that only 10,12 CLA, but not 9,11 CLA, suppressed de novo lipid synthesis within 3–24 h of treatment and cannot be explained by a lack of incorporation of 10,12 CLA, "as both CLA isomers [were] equally incorporate into lipids, albeit at lower levels than other unsaturated FA." The scientists go on to summarize their results as follows:

These and previously published data suggest that 10,12 CLA lowers the lipid content of adipocytes by (1) rapidly decreasing SCD-1 [enzyme responsible for mono unsatuarated fatty acid = MUFA synthesis] activity, thereby reducing the MUFA needed for neutral and compound lipid synthesis (reviewed in Ref. [34]); (2) decreasing PPARγ activity, thereby reducing the expression of adipogenic and lipogenic proteins needed for lipid biosynthesis; or (3) increasing inflammatory lipid metabolites or signals that antagonize glucose and FA uptake and subsequent metabolism.

In that, the results confirm the pro-inflammatory nature of CLA (whenever it "works") I have mentioned in previous blogpost. Chung et al. (Chung. 2005) and Kennedy et al. (Kennedy. 2010) have analyzed the inflammatory effect of CLA before and Obson et al. speculate that the "activation of inflammatory signals such as NFκB that antagonize LXRα, PPARγ and possibly also SREBP-1" could be the underlying mechanism which leads to "decreased activity of lipogenic enzymes essential for FA desaturation and incorporation into neutral and compound lipids within 3–24 h." This is of particular interest, because despite its effect on weight loss, the inflammatory component 10,12 CLA has could eventually turn against you, once overall inflammation passes a certain "healthy" threshold.

Figure 2: Rleative changes in adipocyte fatty acid composition after 3, 24, 72 and 216h of incubation with 9,11 CLA & 10,12 CLA vs. control (data adapted from Obson. 2011)

What's even more questionable, though, is in how far these in-vitro results will translate into real world weight loss. The most recent rodent trial (Arias. 2011) that used 10,12 CLA (0.3% of the diet) alone and in conjunction with resveratrol, for example, did find a modest reduction (-13%) in body fat gain in rats fed with a commercial obesogenic diet, i.e. a diet that is intended to trigger obesity in the animals. On the other hand, the effects of resveratrol (30mg/kg) were more profound and in combination, the two supplements canceled each other out. Thus, it is quite obvious that further research is necessary until we can say something about effective dosages and their respective weight loss effects... I guess I don't need to tell you that the SuppVersity is where you'll hear about these first ;-)

CLA Destroys Body Fat & Increases Endurance! But at Which Costs? It Almost Triples Liver & Doubles Spleen Weight and Increases Blood Glucose & Cholesterol Levels!

Image 1 (Zhu. 2012): The allegedly leaner mouse on the left has a certain gene defect due to which it developed both lipodystrophy (fat loss) and diabetes early in life. Now guess what the mice on the 5% CLA diet developed after 6 weeks?

It is quite funny how the same people who are terrified by the thought that creatine (suggested read "The Pharmacokinetics of Creatine") could damag their kidneys cast caution to the wind, when it comes to magical fat loss pills. "CLA does help fat loss? How can I get more of it?" While the non-existence of conclusive evidence that conjugated linoleic acid does even work in human and the presence of at least 28 isomers of linoleic acid, which are mainly found in the meat and dairy products from ruminants (Banni. 2002) and of which only one seems to "work" is one thing, the ignorance people display for the potential negative side effects high doses (so high that they would maybe help you burn body fat) can have on liver function, glucose metabolism, oxidative stresses and more (cf. Dilzer. 2012) is potentially hazardous.

"CLA is from grass-fed cows so it must be good, right!?"

Sometimes I get the feeling the above statement conveys an accurate representation of the counter-productive black-and-white thinking that is so prevalent among some of the health nuts on the Internet, these days. And in fact, if you take a cursory look at the heavily quoted studies on the effects of CLA on all sort of things ranging from its general antioxidative effects (Reynolds. 2010), over the profane reduction of unaesthetic body fat (in rodents, cf. Wang. 2004) to its purported anti-cancer effects (Tanaka. 2011) it does conjugated linoleic acid is probably second only to vitamin D and fish oil in terms of its contemporary idolatry and, if we regard the fat loss effects in isolation and focus solely on a recent study by scientists from the Department of Food Science at the University of Massachusetts rightly, so!

After all, the results Kim et al. present in the latest issue of Lipids are unquestionably impressive: 70% reduced body fat levels in normal-weight rodents with nothing but 0.5% CLA (as trans-10,cis-12 CLA) in regular rodent chow within 6 weeks!? You can hardly argue that this isn't an impressive result.

Figure 1: Tissue weights (left, large), muscle and liver glycogen content (left small, inset) after and body weight (right, top) as well as food intake (right, bottom) in the course of the 6-week study period (adapted from Kim. 2012)

Aside from the only at first sight remarkable -77% reduction in body fat in the presence of an almost 30% increased food intake (!), the data in figure 1 does yet also confirm other, outcomes we already know from previous studies:

1. only the trans-10,cis-12, but not the cis-9,trans-11 CLA isomer will yield the desired anti-obesity effects
2. instead of healthy weight loss in obese or at least overweight animals, CLA induces what in every other context would be called full-blown lipodystrophy (=pathologic loss of body fat, cf. image 1 and Jaudszus. 2010) in the lean perfectly healthy 129Sv/J mice in the study at hand - and that in the presence of ~30% increased food intake (see figure 1, bottom right)
3. worrisome increases in liver and spleen weight, the latter of which exceed the +76% increase in hepatic glycogen storage capacity by more than a factor 2x (!)

Figure 2: Serum levels of triglycerides, glucose, total cholesterol, non-esterified fatty acids, lactate and blood urea nitrogen in CLA supplemented expressed relative to non-supplemented control (large) and additional figure showing expressions of selected genes from skeletal muscle (based on Kim. 2012)

Let's be honest, if you observed similar increases in food consumption that are accompanied not by gains, but by profound reductions in body fat in your dog, cat, bird, pig or whatever pet you may have, you would interpret that as a clearcut sign that something is awfully wrong with your loved one and seek medical advice right away - correct?

A brief note on the figures in this paragraph: While the examples are hypothetical, the figures I came up with reflect the reductions in body fat and increases in liver weight, glucose and total cholesterol you see in figure 2.

So, why on earth would you even remotely consider going to your local GNC then to get yourself a family pack of CLA cabs in order to get rid of the flab that's still covering your abs? Are you keen on taking yourself to the Dr. after 6-weeks, when you are down from 15% body fat to 4.5% (=70% reduction) and you formerly flabby belly is now bulging because your liver, which does now weigh 4kg instead of the regular 1.5kg, is oozing out from under your ribcage? If that's what you are looking for, you probably won't be worried if your blood glucose shot up from 90 to 112pts and your Dr. is about to prescribe an (in your case particularly unnecessary) statin to sooth your ~50% increased cholesterol levels, either!? You are lean, now! And as Kim et al. euphorically point out your endurance may even increase by 70%(!) while there is still some muscle or liver glycogen or body fat left to fuel the PPAR-gamma driven fat burning wreck you have become...

Image 2: One of the best CLA supplements there is - ok, it's a proprietary blend with small amount of omega-3, omega-6 and important and increasingly scarce vitamins as vitamin A and vitamin K, but you can trust in the divine wisdom of its inventor - mother nature ;-)

Implications: If all the irony has not yet allured you from the idea that you'd better be lean and sick, than somewhat chubby and healthy, you may be disappointed to hear that the human equivalent dose of the trans-10,cis-12 CLA (remember no other form will do this black magic!) is roughly 30g/day and thus probably more expensive than liposuction ;-)

This dosage issue does yet bring us back to where we came from: Grass-fed cows!  After all, it is not only unrealistic, but simply impossible to get this amount of CLA (let alone only t-10,c-12) from your diet- regardless of how much meat and dairy from grass-fed cattle you consume! And based on the the results of the study at hand, you could even argue that nature has rendered that impossible for a good reason, your protection.

So don't pretend you are smarter than nature and stick to your Kerrygold golden grass-fed Irish butter - not so much for the CLA content, though, but for the whole package of synergistically acting power-nutrients nature has put into her original "fat supplement" ;-)

References:

• Banni S. Conjugated linoleic acid metabolism. Curr Opin Lipidol. 2002 Jun;13(3):261-6.
• Dilzer A, Park Y. Implication of conjugated linoleic acid (CLA) in human health. Crit Rev Food Sci Nutr. 2012;52(6):488-513.
• Jaudszus A, Moeckel P, Hamelmann E, Jahreis G. Trans-10,cis-12-CLA-caused lipodystrophy is associated with profound changes of fatty acid profiles of liver, white adipose tissue and erythrocytes in mice: possible link to tissue-specific alterations of fatty acid desaturation. Ann Nutr Metab. 2010;57(2):103-11.
• Kim JH, Kim J, Park Y. trans-10,cis-12 Conjugated Linoleic Acid Enhances Endurance Capacity by Increasing Fatty Acid Oxidation and Reducing Glycogen Utilization in Mice. Lipids. 2012 Jul 11.
• Reynolds CM, Roche HM. Conjugated linoleic acid and inflammatory cell signalling. Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):199-204. Epub 2010 Mar 7.
• Tanaka T, Hosokawa M, Yasui Y, Ishigamori R, Miyashita K. Cancer chemopreventive ability of conjugated linolenic acids. Int J Mol Sci. 2011;12(11):7495-509. Epub 2011 Nov 2. 
• Wang YW, Jones PJ. Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes Relat Metab Disord. 2004 Aug;28(8):941-55. Review.
• Zhu. Ncb5or in Fatty Acid Desaturation and Metabolic Diseases. Zhu Diabetes Research Group. University of Kansas School of Health Professionals. < http://www.alliedhealth.kumc.edu/school/research/zhu/more_info.html > retrieved July 22, 2012

CLA For Weight Loss: Safe, but Ineffective. Conjugated Linolic Acid Fails to Improve Body Composition or Lipid Profile in 8-Week Human Study

The early 2000s were the fat years: "Want to lose fat? Eat fat!" became the credo of more and more nutritional gurus, who put their faithful clients "on" EFAs, PUFAs and a certain fatty acid (FA) that, despite, or rather due to its presence in our food chain, had hitherto received little attention by the medical orthodoxy: conjugated linoleic acid (CLA). All of a sudden, this "unhealthy" trans-fatty acid that can be found in relatively large amounts in high fat milk products, was supposed to become the magic bullet in every dieter's fight against unhealthy or unaesthetic body fat.
So, is the majority of the Americans in the 21st century going to be obese, simply because they are not consuming enough CLA? A recent study from Canadian scientists (Jones. 2011) suggests otherwise.

In a 3-phase crossover trial, Jones et al. recruited 27 overweight (BMI ≥ 25 kg/m²), borderline hypercholesterolemic [LDL-cholesterol (C) ≥ 2.5 mmol/L] men aged 18–60 y, who consumed during three consecutive 8-wk phases (with a 4-wk washout period between each trial) either 3.5 g/d of safflower oil (control) or a 50:50 mixture of trans 10, cis 12 and cis 9, trans 11 (c9, t11) CLA:Clarinol G-80, and c9, t11 isomer:c9, t11 CLA.

Figure 1: Chemical structure of the 2 isomers of conjugated linoleic acid (CLA)
and the unconjugated form linoleic acid (LA)
(image from Kent. 2007)

Body weight, body fat, and lean body mass (all reliably measured by DXA), CLA's effects on fatty acid oxidation, as well as blood lipid profiles and safety biomarkers, including insulin sensitivity, blood concentrations of adiponectin, and inflammatory markers (high sensitive-C-reactive protein, TNFα, and IL-6) and oxidized-LDL were assessed at the beginning and end of each trial. The results were unimpressive:

Compared with the control treatment, the CLA treatments did not affect changes in body weight, body composition, or blood lipids. In addition, CLA did not affect the β-oxidation rate of fatty acids or induce significant alterations in the safety markers tested.

Or, in other words, CLA supplementation @ 3.5g/day did not produce any of the favorable effects potential customers are promised by the advertisements of an industry that thrives on the hopes of overweight of millions of obese individuals world-wide.

A conclusive evaluation of both the effectiveness, as well as the safety of CLA would require further studies using and comparing the effects of different  mixtures of the different CLA isomers that  have been found to exert very different metabolic effects - with the trans-10, cis-12 isomer having a more pronounced effect on PPAR-gamma induced metabolic changes (Hermann. 2009) and more compelling evidence of possible negative side effects, such as increased oxidative stress (Risérus. 2007).

So, after all. The verdict on CLA is still out there! And you know: The SuppVersity is the place, where you will hear about future research first.

Review Claims: CLA & Fish Oil Improve "Anabolic" Effects of Exercise - What Does the SuppVersity Sniff Test Say?

A bigger biceps and less body fat to cover your precious gains? At least for CLA this has in fact been observed in a human study (see figure 1).

About two weeks ago, I stumbled across an interesting paper that had just been published in the peer-reviewed journal Nutrients, filed it and got so much to do that I would almost have forgotten about it. When I was just thinking about which topic to address next, I did yet remember the auspicious conclusion to the abstract, which says "we can hypothesize that fat supplements may improve the anabolic effect of exercise." (Macaluso. 2013). "May" and "hypothesis", those are terms I like and since fish oil and CLA were implicated in the previous lines, I suppose you are going to like it as well. So what would be more obvious than to apply the "SuppVersity Sniff Test" (I am beginning to like this term, Carl often uses on the Science Round-Up) to this ostensibly well-researched review of the literature?

"May improve the anabolic effect of exercise"

Usually things that "may" do just that, namely "improve the anabolic effect of exercise" end up in a pricey and useless testosterone booster.

Check out the overview of the Intermittent Thoughts on Building Muscle and learn how testosterone, growth hormone, IGF-1, mTOR and the rest of the pack orchestrate skeletal muscle hypertrophy and why boosting your testosterone levels from mid will not translate into visible muscle gains (read more)

Personally, I don't know of any test booster though, which boasts that fish oil or CLA were it's main ingredients and without taking away too much of the results of this sniff test, I can already tell you that there is a good reason for why this is the case: It's even less likely to produce significant effects than the next best herb that "grows but in one place" in the Amazonian rain forest, where the CEO of company X harvests it at the hazard of his own life... ah, you know that spiel, so I don't have to repeat it here.

If you take a look at the tables the researchers provide as part of their review and have basic mathematical and reading skills, it's not difficult to count the number of which would remotely support the notion that fish  or CLA supplementation have any effects at all: It's 5 out of 9 for fish oil and 4 out of 7 for CLA. Certainly reason enough to "hypothesize" a bit.

Fish oil is good for your heart, but not for your physique

In the next step we need a little more than to identify those studies with the "no effect" label from the tables and take a the ones we were left with after our initial glance at the data. If we do just that the number of studies we have to look at decreases from 9 to 4 studies, as none of the fish oil studies survives the "Sniff Test", after all, neither

• 

  They probably ain't anabolic either, but could help you to stay lean on a bulk: DHA-phospholipid, as you would find them in krill vs. common fish oil supplements (learn more).

  improved cardiovascular function in the absence of increased endurance performance or recovery in football players (Buckley. 2009)

• a minimal reduction in O2 cost in the absence of effects on the endurance performance in cyclists (Peoples. 2008), 

• improvements in VO2max in previously sedentary men a non-placebo-controlled study (Brilla. 1990)

• a reduced acute phase inflammatory response in a non-randomized non-placebo controlled intervention with average Joes (Ernst. 1991) 

would qualify as convincing evidence for any "anabolic effects" - in fact, even if we were talking about ergognenic effects in general, only the study by Guezennec would survive 2nd phase of the Sniff Test.

Now, what's interesting about the Guezennec study, though, is that the "beneficial" effects (a profound decrease red blood cell deformability; RCD) were hypoxia specific and could easily turn against you. After all, one of the reasons athlete "train high and compete low" (meaning they train at high altitudes with less oxygen in the air and thus hypoxic conditions to outperform the competition at sea level) is that this will increase the production of red blood cells. Now guess why that happens!? Correct! It's a result of the hemolytic effect of hypoxic training... now, what will happens if you copy the 6g /day EPA-max supplementation regimen of the 19-38 years old guys in the Guezennec study? Right, this effect will be absent. I wouldn't go so far and call this "ergolytic", but you could certainly make a point that huge amounts of EPA are - at least in this scenario - anti-ergogenic.

So what about CLA, then? Isn't that simply a fat burner

So, if even the widely hailed fish oil has little data to support its usefulness as an ergogenic supplement for athletes and aspiring physical culturists, what about CLA, then? I mean, we all know that the benefits researchers observed in human trials were miles apart from what they had expected to happen based on previous experiments in rodents (click on the image to the right to be redirected to a study, where the CLA treated ice dropped 77% body fat and did nevertheless display statistically significant increases in endurance capacity).

Adequate dosing still remains an issue

These discrepancy in terms of the body fat reducing effects of conjugated linoleic acid supplementation, as Dilzer and Park pointed out only recently, at least in parts a result of insufficient doses:

In July 2012 I wrote about what I believe is the unquestionably most impressive study on the fat burning and endurance enhancing effects of conjugated linolic acid. 77% body fat reduction - that's bordering lipodystrophy. The dosage used in this study would be roughly equivalent to 30g/day for human being and supports the notion that profound effects are only observed with amounts of CLA that have yet not been administered to humans in controlled trials (learn more)!

"Studies with mice used diets containing 0.5 w/w%* CLA, which is equivalent to about 56 g CLA/day/70 kg (Malpuech-Bruger. 2004). Most human studies used CLA doses ranging between 0.7 g and 6.8 g per day, which is lower than doses used in mice." (Dilzer. 2012)

*Addendum: Anonymous pointed out correctly, that the figures in the above quotation (which is dirertly from the FT) are inconsistent. 0.5% would be only 5.6g. I guess that's a typo in the Dilzer study, because the Malpuech-Bruger study they reference says "a daily intake of 0.70 g/kg body mass was effective in mice". (Malpuech-Bruger. 2004) - sloppily as they are, they don't say that this is already in human equivalents, though. That becomes clear in the next sentence only, which says "A value of 0.70 g/kg body mass in humans would correspond to a daily intake of 56 g of CLA." (ibid.) The July 2012 study I reference under the image to the right used a HED of ~30g (learn more), so even if the exact figures are questionable, the argument obviously still holds.

Since the same goes for studies investigating the "anabolic" effects the abstract to Macaluso et al.'s review explicitly mentions, chances are that increases in endurance performance, as they were observed in the previously mentioned rodent study (read the full story, here), were likewise species or at least dosage specific.

Is CLA "anabolic" or at least ergogenic?

If we take a look at the 7 studies the researchers included in their review (I guess you will be hard-pressed to find more than those seven, as CLA is not exactly the typical supplement researchers use as an ergogenic), we can easily exclude three of them. In these studies that were conducted on healthy young women, trained male bodybuilders and physically active men and women, supplementation with 3g, 6g and 3.9g/day of CLA did exactly nothing.

This leaves us with a set four studies to take a closer look at - three of them report improvements in body composition, two of them also observed increases in endurance performance and a single one even found "slight increases in testosterone":

• Improvements in body composition were observed by Thom (2001), Colakoglu (2006) and Pinkonski (2006); all studies were placebo controlled and the participants were physically active or at least healthy men (only in the Thom study) and women who consumed 1.8, 3.6 and 5g of CLA per day.
  
  While the former two studies by Tho and Colakoglu used exhaustive and medium intensity endurance programs, the study by Pinkonski et al. used a stardardized full-body workout with 12 exercises ranging from leg presses, bench and shoulder presses, to lat pull downs, biceps curls, and some core exercises. Each exercise was performed three times per week consisting of 3–4 sets of 4–10 repetitions at approximately 75–90% of one-repetition maximum (1RM).

  

  Figure 1: Relative changes in body composition biceps and quadriceps size and strength parameters after 7 weeks of serious strength training with or without 5g of CLA per day (Pinkoski. 2006)

  This protocol and the high number of study participants (76 men and women) and their training status - the majority had more than 2 years of weight training experience under their belts - make the results of the Pinkoski study so interesting for us. The results, on the other hand (cf. figure 1), are not exactly earth shattering, especially in view of the fact that only the fat loss and the increase in biceps size reached statistical significance and that despite a pretty high number of participants. Whether or not CLA really is "anabolic" and not "just" a mediocre fat burner has thus still to be determined.

Figure 2: Increases in cortisol (top) and testosterone (bottom) and respective increases in lean body mass in response to a 12-week hypertrophy oriented resistance training program (West. 2012)

• Increases in testosterone, as Macaluso et al. observed them in 10 "physically active" male subjects (age, 27.4) in a previous study in response to 6g CLA per day, on the other hand, would probably qualify as "anabolic" if the latter had not been measure right the workouts, as part of a short 3-week study with no corresponding effects on body composition (Macaluso. 2012).
  
  The latter should actually not come as a surprise to any seasoned SuppVersity student. After all you've learned that (1) endocrine induced changes in body composition take their time in the Intermittent Thoughts on Building Muscle, that (2) the role of  testosterone levels in the normal range in the whole process is fundamentally overrated and (3) that the seminal paper by West & Phillips, on which the data in figure 2 is based, clearly refutes the notion that post-workout increases in testosterone have any impact on skeletal muscle hypertrophy.

If we also take into account that numerous rodent studies do in fact support the notion that CLA posses "ergogenic",  yet not necessarily "anabolic" qualities. Macaluso et al. are certainly correct, when they conclude their paper with the scientific equivalent to "And they lived happily ever after" stating that "additional research".

---

Milk from pastured cows has a relatively high amounts of both, CLA and DHA + EPA. The absolute amounts are however so low that you would probably have to drink more than the notorious gallon of milk per day to see any effect - and let's be honest, even if CLA + DHA make a good fat burner, the gallon of milk certainly makes a better weight gainer ;-)

Bottom line: I guess, you'd like to hear a supplement recommendation now, right? Well, as far as ergogenic and/or anabolic effects are concerned, CLA is unquestionably the more promising fatty acid off the "two" (actually we are talking about four fatty acids, here: DHA + EPA = fish oil and cis-9,trans-11 and trans-10,cis-12 CLA). CLA's anti-PPAR-gamma effect, which is probably responsible for the reductions in insulin sensitivity and detoriations of the lipid metabolism that have been observed in numerous studies (only trans-10,cis-12 CLA), is probably not so much of a problem for lean, physically active people and the upside of the PPAR-gamma blockade is a reduced rate of fat storage....

Ah, you see I am diverting to the fat loss effects again. And if we are honest, the results of this review do actually only confirm that what you've read here at the SuppVersity roughly 3 months ago the combination of CLA + DHA could turn out to be a safe and effective fat burner (learn more), if we would finally see adequately doses, long(er) term supplementation trials in humans.

As ar as the "anabolic" nature of either of them, i.e. EPA + DHA or cis-9,trans-11 and trans-10,cis-12 CLA. The jury may still be out there, but the verdict is - at least in the case of regular fish oil almost certainly "not guilty", .. ah I mean, "not anabolic".

References:

• Brilla, L.R.; Landerholm, T.E. Effect of fish oil supplementation and exercise on serum lipids and aerobic fitness. J. Sports Med. Phys. Fitness 1990, 30, 173–180.
• Buckley, J.D.; Burgess, S.; Murphy, K.J.; Howe, P.R. DHA-rich fish oil lowers heart rate during
  submaximal exercise in elite Australian Rules footballers. J. Sci. Med. Sport 2009, 12, 503–507. 
• Colakoglu, S.; Colakoglu, M.; Taneli, F.; Cetinoz, F.; Turkmen, M. Cumulative effects of conjugated linoleic acid and exercise on endurance development, body composition, serum leptin and insulin levels. J. Sports Med. Phys. Fitness 2006, 46, 570–577.
• Dilzer A, Park Y. Implication of conjugated linoleic acid (CLA) in human health. Crit Rev Food Sci Nutr. 2012;52(6):488-513.
• Ernst, E.; Saradeth, T.; Achhammer, G.  n-3 fatty acids and acute-phase proteins.  Eur.  J.  Clin.
  Invest. 1991, 21, 77–82.
• Guezennec, C.Y.; Nadaud, J.F.; Satabin, P.; Leger, F.; Lafargue, P. Influence of polyunsaturated fatty acid diet on the hemorrheological response to physical exercise in hypoxia.  Int.  J.  Sports Med. 1989, 10, 286–291.
• Lenn, J.; Uhl, T.; Mattacola, C.; Boissonneault, G.; Yates, J.; Ibrahim, W.; Bruckner, G. The effects of fish oil and isoflavones on delayed onset muscle soreness. Med. Sci. Sports Exerc. 2002, 34, 1605–1613. 
• Macaluso, F.M.;  Catanese, P.; Ardizzone N.M.; Marino Gammazza, A.; Bonsignore, G.; Lo Giudice, G.; Stampone, T.; Barone, R.; Farina, F.; Di Felice,  V. Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo. J. Strength Cond. Res. 2012, 26, 1667–1674. 
• Macaluso F, Barone T, Catanese P, Carini F, Rizzuto L, Farina F, Di Felice V. Do Fat Supplements Increase Physical Performance? Nutrients 2013; 5:509-524.
• Malpuech-Brugère C, Verboeket-van de Venne WP, Mensink RP, Arnal MA, Morio B, Brandolini M, Saebo A, Lassel TS, Chardigny JM, Sébédio JL, Beaufrère B. Effects of two conjugated linoleic Acid isomers on body fat mass in overweight humans. Obes Res. 2004 Apr;12(4):591-8.
• Oostenbrug, G.S.; Mensink, R.P.; Hardeman, M.R.; De Vries, T.; Brouns, F.; Hornstra, G. Exercise performance, red blood cell deformability, and lipid peroxidation: Effects of fish oil and vitamin E. J. Appl. Physiol. 1997, 83, 746–752.
• Peoples,  G.E.;  McLennan,  P.L.;  Howe,  P.R.;  Groeller,  H. Fish oil reduces heart rate and oxygen consumption during exercise. J. Cardiovasc. Pharmacol. 2008, 52, 540–547..
• Peoples,  G.E.;  McLennan,  P.L.;  Howe,  P.R.;  Groeller,  H. Fish oil reduces heart rate and oxygen consumption during exercise. J. Cardiovasc. Pharmacol. 2008, 52, 540–547. 
• Pinkoski, C.; Chilibeck, P.D.; Candow, D.G.; Esliger, D.; Ewaschuk, J.B.; Facci, M.; Farthing, J.P.; Zello, G.A. The effects of conjugated linoleic acid supplementation during resistance training. Med. Sci. Sports Exerc. 2006, 38, 339–348.
• Thom, E.; Wadstein, J.; Gudmundsen, O. Conjugated linoleic acid reduces body fat in healthy exercising humans. J. Int. Med. Res. 2001, 29, 392–396.
• Toft, A.D.; Thorn, M.; Ostrowski, K.; Asp, S.; Moller, K.; Iversen, S.; Hermann, C.;  Sondergaard, S.R.; Pedersen, B.K. N-3 polyunsaturated fatty acids do not affect cytokine response to strenuous exercise. J. Appl. Physiol. 2000, 89, 2401–2406.
• West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2012 Jul;112(7):2693-702. 

Grass-Fed Beef: Does CLA make the difference? Probably Not.

You certainly have heard of the benefits of the meat of grass-fed, i.e. naturally nourished, cows. Well, although I do not want to question its general superiority to corn-fed high omega-6 meat, it probably is not the CLA content which distinguishes good from not so good meat sources.

A recent study, which was conducted by scientists from the Iowa State University (Brown. 2011), scientists investigated the effect of a "balanced nutritionally complete diet" (31% energy from lipid, 13% from protein, and 54% from carbohydrate) with either high (1.17 g/d) or low (0.35 g/d) CLA content on various health parameters of 18 healthy women aged between 20 to 39 years over a 8 weeks period. These are the results:

The CLA diet did not result in any differences in insulin sensitivity, body composition, circulating blood lipids, or other measured disease risk factors as compared with the control diet.

Accordingly, the scientists concluded "that a diet naturally enriched with over a 3-fold increase in CLA from pasture-fed cattle "did not provide a health benefit when compared to "a similar diet composed of foods from grain-fed cattle."

While these results stand in line with the generally equivocal findings on possible health benefits from CLA supplementation in human beings, it remains questionable whether with a "nutritionally less complete [from a government standpoint]" diet, i.e. a diet with less carbohydrate content and a consequently higher meat consumption, the results would not have been totally different.

Figure 1: Fatty acid composition of grass-fed vs. conventional meats.

All that aside, a study by Irish scientists (McAfee. 2011) showed that the CLA content of grass-fed vs. conventional meat is not all that different, anyway. According to McAfee et al. it is rather the n-3 PUFA content of grass fed meat which "can significantly increase consumer plasma and platelet LC n-3 PUFA status" and may thus have a positive influence on metabolic risk factors in general and n-6 to n-3 PUFA ratio in particular.