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. 2013a).

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. 2013b)

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. 2013)

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. 2013b)

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. 2013b)

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. 2013a;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. 2013b Nov 21.

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 2013 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. 2013)

*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 2013 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. 2013)

• 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. 2013).
  
  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. 2013;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. 2013, 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. 2013 Jul;112(7):2693-702. 

Science Round-Up Seconds: Optimal Health & Fitness Best Promoted W/ Intense Exercise. News on PUFAs & Thyroid Metabolism. Manganese the Anti-Sugar Glue Mineral!?

There may be a hitherto overlooked "enzymatic connection" between low thyroid function (spec. "low T3 syndrome" or starvation-/overtraining-induced reductions in thyroid levels) and "insufficient" levels of the long-chain varieties of both, omega-3 (EPA, DHA), as well as omega-6 (GLA, ARA) fatty acids.

I must admit that Carl & I did much to my own surprise cover more ground than I thought we would - and that despite his lengthy rant about the FDA ;-) That said, there is still enough for a second serving, aka the "Seconds", featuring news like:

• The optimal exercise for health and fitness is intense - SuppVersity readers & Superhuman Radio listeners knew it all along, the comfort zone won't enforce adaptation
• PUFAs and the thyroid - insufficient conversion of LA and ALA with low T3 levels; probably also relevant everyone who enjoys starvation and overtraining
• Manganese an anti-sugar glue mineral - study shows manganese protects blood vessels in a high glucose environment from the from monocyte adhesion and subsequent endothelial dysfunction

Contrary to previous shows it does not really matter, whether or not you have already or are still going to listen to the show. If you want, or your schedule doesn't allow otherwise, you can very well start with the Seconds, though - and that despite the fact that the author(s) of book of etiquette probably won't appreciate that ;-)

Scientists listen to the SuppVersity science round: Working out glycogen-depleted rules

8x Increase in "Mitochondria Building" Protein PGC1-Alpha W/ Medium Intensity Exercise in Glycogen Depleted Elite(!) Cyclists:- that's the headline of an October 2013 SuppVersity post

(Taanaka. 2013) -- The headline of this paragraph is obviously meant to be funny, but still. It's a funny coincidence that Hiroaki Tanaka, Kazuhiro Morimura and Keisuke Shiose from the f Fukuoka University in Fakuoka, Japan have just published a review on what the title tells us is An optimal exercise protocol for improving endurance performance and health and the protocol they suggest is basically very similar to the one(s) you will have heard about on the Science Round-Ups of December 8 and December 21, in which we broached the same issue of training in a glycogen depleted state, I also addressed in a post from October 2013 (see image on the right).

Obviously the review that has just been published in the The Journal of Sports Medicine and Physical Fitness has been written before my article, but it's still nice to see that the conclusions the Japanese researcher draw are virtual identical to what you read and heard on the SuppVersity and Super Human Radio, before:  

1. Tell me about efficacy: 4-6×30 s supramaximal sprint cycling Wingate tests are as effective as 40-120 min exercise session s at 65% of VO2Peak (Burgomaster. 2008); 7×30 s “all-out” bouts and 3×20 min bouts at approximately 87% of VO2peak could induce a similar increase in PGC-1α (Psilander. 2010); learn more about HIIT
   The optimal exercise protocol to improve health and endurance performance was discussed in re-lation to exercise-induced gene expression of PGC-1α.
2. Training intensity is a critical factor in PGC-1α gene expression and requires trainees to work out at a high(er) intensity broaching the lactate threshold (=no hours of endurance training, but glycolytic exercises such as sprinting or plyometrics)
3. HIIT does  not simply offer a way to meet the criteria in (2), it is also highly time efficient and improves aerobic capacity to a much greater extend than classic steady state cardio training
4. Training a glycogen depleted state renders submaximal continuous exercise a viable alternative to high intensity workouts.

Actually it would be ideal if I wouldn't have to repeat that whenever this issue comes up, but just to make sure: Do never forget that training  glycogen depleted is something like an intensity technique. Just like training past failure on every set, heavy eccentrics or planned phases of deliberate overreaching, it can set you up for overtraining and the Athlete's Triad, when your diet and / or recovery times are off.

PUFAs and the thyroid - insufficient conversion of LA and ALA with low T3 levels

(Swenne. 2013) -- This is not what the Peat-anians (or whatever you may call the friends of Dr. Ray Peat's theories may call), are now thinking about. At least at first sight, it would appear that it's quite the opposite of Peats anti-thyroid theory of polyunsaturated fatty acids (PUFAs).

Figure 1: Illustration of the role of the blocked (X) desaturase (DS) enzymes Delta-6 and Delta-5 in the formation of long-chain omega-6 (top) and omega-3 (bottom) fatty acids

After all, the results, Swenne and Vessby present in a paper that has been published only a couple of days ago in Acta paediatrica point towards an inhibitory effect of low thyroid function (specifically low triiodothyronine = T3 levels) on PUFA metabolism.

Stupid question of the day: "But Arachidonic Acid (ARA) is bad anyway, so why would I care - I mean, I take my fish oil" I am fully aware that the screwed up worshiping of omega-3 and the overgeneralized demonization of omega-6 fatty acids make questions like this appear logical, if not "smart". In fact, they do yet only reveal the public ignorance towards the complex interactions and the importance of proper ratios of both types of polyunsaturated fatty acids.

In an exercise scenario comprising a 4x/week classic body building strength training regimen, for example, the ingestion of 1g of arachidonic acid on a daily basis has been shown to have anti- not pro-inflammatory effects (-15% IL-6; Roberts. 2007)

Upon closer scrutiny of the actual data, it does yet turn out that the starvation induced alterations of omega-3 essential fatty acid (EFA) metabolism the Swedish scientists observed in 227 adolescents with eating disorders went hand in hand with the down-regulation of T3 levels. This observation alone does therefore not suffice to settle the "chicken or egg question" (i.e. what comes first?). The researchers' analysis of the activity of the desaturase enzymes (see figure 1), which convert the short chain omega-3/6 to long-chain omega-3/6 fatty acids would yet suggest a causative relationship between the reductions in active thyroid hormone and the subsequent deficiency of the long-chain polyunsaturated fatty acids EPA & DHA (omega-3) and GLA and arachidonic acid (omega-6). Now things become really interesting, when we also take into consideration that previous studies have shown that

"[i]nsulin appears to stimulate both desaturases, while hormones that increase blood sugar concentrations such as glucagon, adrenalin and corticosteroids are inhibitory for both enzymes." (Swenne. 2013)

This in turn brings us right back to the Athlete's Triad (read more about the Athlete's Triad in the respective SuppVersity Special) where the continuous lack of readily available energy results in low insulin levels and chronically elevated glucogon, adrenalin and corticosteroid levels, so that long-chain PUFA supplementation (and this includes the omega-6 fatty acids GLA and ARA) would appear to be indicated for (chronically) overtrained athletes, as well.

Manganese protects endothelial cells of diabetic rodents

(Burlet. 2013) -- In the latest issue of the Journal of Biological Chemistry, Elodie Burlet and Sushil K. Jain from the Louisiana State University Health Sciences Center report that administration of a whopping dose of 16 mg/kg body weight of manganese chloride (this equals ~4mg of elemental manganese) to Zucker diabetic fatty rats (standard model of diet-induced diabetes) significantly reduced the binding of immune cells to the endothelium and will thus have an ameliorative effect on the development of cardiovascular diseases.

As the data in figure 2 goes to show you the human equivalent of ~50mg/day elemental manganese did also induce statistically highly significant reductions in cholesterol and - what's probably of greater real-world relevance in view of the CVD-risk - a 60% reduction (!) in triglycerides in the diabetic rodents.

Figure 2: Relative expression of markers of binding of immune cells to the endothelium and cholesterol and triglyceride levels in diabetic rodents with or without additional 4mg/kg elemental manganese in their drinking water (Burlet. 2013)

Among the plethora of (trace-)minerals manganese certainly is one of the least known and that despite the fact that it plays an absolutely crucial role in blood glucose management. In view of the fact that it is known to raise not decrease blood glucose, it is however understandable that detailed information about this trace mineral the levels of which are tightly regulated by our bodies is scarce - I mean, the number of people suffering from hypoglycemic episodes is several magnitudes smaller than the number of (pre-)diabetics. Moreover, the beneficial effects on blood lipids have also been confirmed in different scenarios such as a rodent model of menopause (Bae. 2011)

Table 1: Average manganese content of selected foods (download full list from the USDA, here)

Since manganese also figures in  the enzymatic cascades which underly protein metabolism, bone formation, the synthesis of the neurotransmitter GABA and is an essential constituent of the eponymous manganese superoxide dismutase, one of the most important enzymes in the endogenous anti-oxidant system of the mitochondria, it is actually no wonder that manganese is officially considered one of the "essential trace minerals". With an adequate intake of 2.3mg for men and 1.8 mg for women (according to the Linus Pauling Institute) and it's abundance in Western type diets (>10mg/day), full-blown deficiencies are yet rare.

A 1987 study by Friedman et al. did yet show that a diet that contains insufficient amounts of manganese will result in skin rashes and pathologically low cholesterol levels. Since high levels of manganese are also implicated in the development of Parkinson's or rather a "Parkinson like disease" that's induced by manganese accumulation, but does not involve degeneration of midbrain dopamine neurons, supplementation with larger amounts of manganese without knowing one's dietary intake (better even tissue and serum levels), supplementation high(er)-dose supplementation is thus counter-indicated. Whether human type II diabetics can benefit from supplementation and which dosages are save and effective will still have to be elucidated.

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That's it already: In case you want more short news, even before the official installment of "On Short Notice" is posted tomorrow (don't as me what's going to be in there, I have no clue as of yet ;-), I suggest you visit the SuppVersity Facebook Page and check out these

• NON-ergogenic gadget of the week - Holographic wrist band meant to increase performance turns out to worsen performance compared to performance worse than "placebo"  (read more)
• The anti CVD taurine <> cholesterol connection - High serum taurine levels protect people with abnormally high cholesterol from cardiovascular disease (read more)
• Tennis elbow? Ultrasound and laser therapy show promise in treatment of medial and lateral epicondylitis, review says. (read more)
• Milk - What's good for the young ones can't be bad for the elderly, right? Right! Japanese 70+-agers' BMI and HDL levels benefit from milk consumption (read more)

as well as the other news I  have already posted + those that are going to appear within the next 24h and before the short news are even written (let alone published ;-).

References: 

• Bae YJ, Choi MK, Kim MH. Manganese supplementation reduces the blood cholesterol levels in Ca-deficient ovariectomized rats. Biol Trace Elem Res. 2011 Jun;141(1-3):224-31.
• Burgomaster KA, Howarth KR, Phillips SM, Rakobowchuk M, Macdonald MJ, McGee SL, Gibala MJ. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J Physiol. 2008; 586: 151-160.
• Burlet E, Jain SK. Manganese supplementation reduces high glucose-induced monocyte adhesion to endothelial cells and endothelial dysfunction in zucker diabetic fatty rats. J Biol Chem. 2013 Jan 17.
• Friedman BJ, Freeland-Graves JH, Bales CW, et al. Manganese balance and clinical observations in young men fed a manganese-deficient diet. J Nutr. 1987;117(1):133-143.
• Psilander N, Niklas P, Wang L, Li W, Westergren J, Jens W, Tonkonogi M, Michail T, Sahlin K, Kent S. Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise. Eur J Appl Physiol. 2010; 110: 597-606.
• Roberts MD, Iosia M, Kerksick CM, Taylor LW, Campbell B, Wilborn CD, Harvey T, Cooke M, Rasmussen C, Greenwood M, Wilson R, Jitomir J, Willoughby D, Kreider RB. Effects of arachidonic acid supplementation on training adaptations in resistance-trained males. J Int Soc Sports Nutr. 2007 Nov 28;4:21.
• Swenne I, Vessby B. Relationship of Δ(6) -desaturase and Δ(5) -desaturase activities with thyroid hormone status in adolescents with eating disorders and weight loss. Acta Paediatr. 2013 Jan 19.
• Tanaka, H, Morimura K, Shiose H. An optimal exercise protocol for improving endurance performance and health. J Phys Fitness Sports Med. 2013; 1(4): 595-604.