Mercury in Fish NOT Harmless, Regardless of Cysteine, Selenium, EPA or DHA! Plus: No Cardioprotective Effect of Omega-3 in Men With Higher Hair Mercury Levels

Image 1: Nice! Luckily nothing you will catch everyday, because if you ate this little bastard, a Tile Fish from the Gulf of Mexico, everyday, you could - in the worst case - be consuming 933µg of mercury with every 250g serving!

"Mercury from fish is not a problem, because you get plenty of selenium to counter it... moreover it's mostly protein bound, already..." - Another Myth Busted!? I must admit, I did believe (without ever checking scientific references) the common mantra that the mercury (Hg) content of fish would not actually be a problem, as long as there is enough selenium (Se) in the fish to "buffer" the Hg load. Now, this certainly makes sense and even very recent studies confirm that the effective uptake is reduced with higher Se:Hg ratios (e.g. Calatayud. 2013). Moreover, the notion that selenium exerts a protective effect is bolstered by data from various indigenous populations in the Brazilian Amazon (Lemire. 2011).

Cysteine, Omega-3 & Selenium? Won't help!

Unfortunately, a recent study by a group of scientists from the Arcachon Marine Station in Acachon, France, does now remind me why I have made it a rule over the year to question every conventional wisdom regardless how logical it may seem (Bourdineaud. 2013). The researchers fed a group of mice diets that contained either 4.88% fishmeal powder that had been produced from the flesh of H. aimara fish that had been caught in the Sinnamary River in French Guiana and contained 5µg Hg/g or a control diet which had slightly less protein (14.2% vs. 18.1%) and contained higher concentrations of EPA(10x), DHA(>30x) and DPA (>5x) - obviously right from the fish.

Figure 1: Fatty acid composition of the diets (left) and breakdown of the omega-3 part of the diets (rel. to total PUFA content - right; data calculated based on Bourdineaud. 2013)

In addition, the fish diet contained methylmercury in its purportedly less toxic largely peptide bound form, methylmercury-cysteine (MeHg-cysteine), while the mercury the scientists had added to the control diet was the purportedly more toxic salt form of mercury, i.e. methylmercury-chloride (MeHgCl).

Which fish contains how much mercury? I knew you would ask this and in essence it is impossible to answer without analyzing the very same fish, because as we are about to see, even the same species from the same fishing ground won't do.

Figure 2:  Mean (bottom axis!) and max (top axis!) mercury content (mg/kg) in fish (based on FDA Monitoring Program. 1990-2010)

Now, I would be a hilarious smartass if I left you with this "you never know" statement, but would still advice you to regard the following information as very broad estimations and heavily generalized categorizations:

• the worst offenders: Mackerel, King Shark, Swordfish & Tilefish (from the Gulf of Mexico) with mercury levels in the 1,000µg/kg range - 250g of those and you are on par with the mice in the study
• examples from the rest of the pack (see figure 2): It is plain to see that even fish with a relatively low mean mercury concentration such as Pollock (mean: 31µg/kg) can be laden with mercury, if you just pick the wrong one (max: 780µg/kg!)

Regardless of in some cases 20x higher outliers, you are probably on the safer side of things, when you pick one of the fish / shellfish that are on top of figure 2 and thus have the lowest mean mercury concentration.

How much did the mice consume? With  253 and. 237µg/kg in the MeHgCl and fish diets the mice in the study at hand consumed ~1µgof mercury per day this corresponds to a human equivalent dose of approximately 3.2µg/kg or 263µg/day for a 80kg adult.

Next to the aformentioned selenium argument (the selenium content of the fish diet was likewise higher 480 vs. 300µg/kg), the presence of MeHg-cysteine instead of MeHgCl and the healthy fish oils, are arguments #2 and #3 in the unquestionably convincing "mercury from fish is not a problem" argument.

It takes 8 weeks of mercury expose for the mice to go havoc - only from fish, though!

The mice were maintained on the diets for either 29 or 58 days. At the end of the exposure period, mice were subjected to an open-field maze test, in order to quantify anxiety levels, and to a Y-shaped maze test, to assess cognitive ability. Thereafter, the rodents were anesthetized and tissue samples were taken. Here are the main findings:

• within the first 10 days of the feeding period, the mice on the Hg containing diets gained  weight faster than rodents on a non-Hg control diet - 4%  and 7.4% more weight gain in the MeHgCl and Fish group, respectively; afterwards the weight development was identical
• both Hg diets lead to significant increases in serum and tissue MeHg with the kidneys being the "preferred" storage place with a tissue concentration of 7.3 and 6.8mgHg/g in mice fed the MeHgCl and fish diets, respectively (17x and 16x higher than in controls); there was a statistically significant inter-group difference only in the striatum, which accumulated ~30% less methylmercury in the fish group compared to the MeHgCl group
• significant behavioral abnomalies did only occur on the 2nd test at the end of the study period (day 58) and were exclusive to the Fish group, which also exhibited an increased dopamine metabolic turnover in the hippocampus

In the end, there is little to add to the scientists somewhat disillusioned conclusion that despite the fact that they had had good reason to assume (like you and I ;-) that the mercury induced metabolic and neurocrine perturbations in the Fish group "should appear less severe than that observed with the MeHg-containing diet [..] the present study" falsified the original hypothesis and suggests that rather than being less toxic, the peptide bound MeHgCysteine in fish is even more toxic than its chloride bound counterpart.

"Mice are nice, but what about men? I am sure know fish oil protects us!" Not really, no...

Another of the pieces that's still missing to get at least a preliminary grasp of the fish oil, selenium, mercury-toxicity puzzle, comes from a recent study that's been conducted at the University of Eastern Finland in Kuopio, and in the course of which the scientists analyzed the relation of mercury exposure (as quantified by hair mercury levels), long-chain poly-unsaturated fatty acids (LC-PUFA = omega-3) levels and individual risk of CVD, in general, and sudden cardiac death, in particular, in a group of 42-60 year-old men who had been free of any adverse cardiovascular events at baseline in 1984-1989 (Virtanen. 2013); and the results Virtanen et al. present in a paper in the July edition of the free medical Journal PloS One are astonishing, to say the least:

• of the three long-chain polyunsaturated fatty acids, EPA, DHA and DPA (=docosapentaenoic acid), only the latter, i.e. DPA, correlated significantly with the absence of sudden cardiac death within the time to the follow up (p < 0.01)
• the by far best predictor of whether or not the study participants would pass away before their time was yet the hair mercury content, which was 53% higher in those unlucky 91 patients who died from sudden cardiac death, than in the "survivor" group (2.85µg/g vs. 1.86µg/g)

Before we take a closer look at how this translates into the calculated hazard risks, I do yet feel inclined to draw your attention to some more basic, and not statistically processed baseline characteristics of the participants with the highest (4.96–15.59%) serum LC-PUFA values.

Don't deduce from pairs of associations!

A brief lesson in interpretation of scientific data - If A & B, and A & C, then B & C... NO!

Actually this thing about associations and logical reasoning is nothing extraordinary, but I thought it may be worth reminding you not to make the false assumption that  "if A is associated with B and A is associated with C, then B must be associated with C, as well", or to give you a more concrete example: If people with high LC-PUFA levels have higher incomes and people with high LC-PUFA levels have higher mercury levels, then people with higher mercury levels should also have higher incomes"

I see, now you are laughing, but I bet, everyone of us has once fallen for a similar mistake, esp. if the result of this falsely applied deduction was in support of your original hypothesis.

The study participants with the highest long-chain omega-3 levels in their blood also had the highest...

• physical activity (borderline significant p = 0.06)
• income (p < 0.001) and eduction (p = 0.01)
• fish, fruit, berry and vegetable intakes (p < 0.001)
  
• the highest hair mercury concentration (p < 0.001)
• the highest alcohol intake (p < 0.001, and 53% more than those w/ 1.7-3.9% LCPUFA)
• the highest rates of coronary heart disease in the family (p = 0.03, but only 6% difference total)

Despite the fact that higher mercury levels in the had were thus obviously associated with higher omega-3 levels in the blood, it would be preliminary to assume that all other of these variables, such as a higher income, or the physical activity would also be associated with higher mercury levels. And in fact, the exact opposite is the case,...

• higher income,
• higher education,
• higher fruit and vegetable intake and
• higher physical activity
  

... all of which were also associated with higher omega-3 levels in the blood were statistically significantly associated with lower mercury levels!

Mercury, fish oil and heart disease a marvelous triumvirate 

Let's get back to the harzard ratios and how fish oil intake and methylmercury intoxication interact in terms of the sudden cardiac death risk of the middle-aged (mean age at baseline 52.1 years) study participants.

Figure 3: Hazard ratios relative to lowest - adjusted for age and examination year (model 1),  adjusted for model 1 and body mass index, pack-years of smoking and alcohol intake (model 2),  adjusted for model 2 and hair mercury content (model 3); and hazard ratios associated with each 0.5%  unit increase in serum LC-PUFA, stratified by the median hair mercury content (calculated based on model 2, right; data compiled based on Virtanen. 2013).

While there is certainly much that could be said about the overall study outcome, there are three things that are remarkable, novel and particularly noteworthy in the data in figure 3:

• EPA is not only useless, without additional statistical shenanigan, it is even associated  (yet non-significantly) with an increased risk of CVD, when it's really high (+2% risk increase for each unit increase in EPA).
• DHA is only protective, when the methylmercury levels are low (model 3 in figure 2 adjusts for that), when this is the case, however, each unit increase in DHA is associated with a whopping -19% decrease in
• the statistical significance of the protective effects of DPA against sudden cardiac death is lost, when the data is adjusted for body mass index, pack-years of smoking and alcohol intake.

If we take the interactions with the hair (and thus presumably bodily) mercury load into consideration (see figure 3, right), it becomes obvious that hair mercury levels above the >1.28mg/g range renders both EPA and DHA practicually useless.

"Where do I get this DPA from; and what's that anyway?"

Figure 4: Enzymatic cascade from ALA to DHA; if you take a closer look the cascade does also explain why an increased conversion of ALA can competitively reduce the generation of EPA (see Portolesi. 2007)

Unfortunately, EPA and DHA are the two major forms of long-chain omega-3 fatty acids you will find in supplemental and dietary fish oil, so that your body will have to derive the DPA via Δ5-desaturase from EPA on its own (Leslie. 1985; see my illustration in figure 4 to get an idea of the whole cascade). This is not impossible, but obviously a rate limited step that could be avoided by direct supplementation, which is in fact something Miller et al. have done, only recently, and, as you have read, right here at the SuppVersity (see "On Short Notice" from July 29, 2013), which remarkable success (Miller. 2013).

Whether the beneficial effects of DPA are in fact related to its "reservoir function", Miller and his colleagues speculate about, cannot be said but would certainly constitute an intriguing research question for another rodent trial, maybe the mice in the Bourdineaud study would have been normal if they had had more DPA in their diets (see figure 1, right)

Bottom line: Until more scientific data is available (and probably still thereafter), there are actually three practical implications from this study you should bear in mind: (1) It does not make sense for anyone who carelessly shovels down tons of potentially mercury loaden fish to freak out about a tiny amalgam filling; (2) if you intend to benefit from the cardioprotective effects of fish oil, you better make sure that you are getting supplements and fish that have been tested for mercury, because the selenium alone obviously won't do the trick and save your ass... ah, pardon, your heart ;-) and (3) if you don't eat the worst offenders on a daily basis the benefits will probably still outweigh the negatives: I have recommended to fatty fish once or twice a week numerous times in previous articles and I don't see why these results would change anything about the recommendation.

References:

• Bachmanov AA, Reed DR, Beauchamp GK, Tordoff MG. Food intake, water intake, and drinking spout side preference of 28 mouse strains. Behav Genet. 2002 Nov;32(6):435-43.
• Bourdineaud JP, Marumoto M, Yasutake A, Fujimura M. Dietary mercury exposure resulted in behavioral differences in mice contaminated with fish-associated methylmercury compared to methylmercury chloride added to diet. J Biomed Biotechnol. 2013;2013:681016. Epub 2013 Jul 26.  
• Calatayud M, Devesa V, Virseda JR, Barberá R, Montoro R, Vélez D. Mercury and selenium in fish and shellfish: Occurrence, bioaccessibility and uptake by Caco-2 cells. Food Chem Toxicol. 2013 Aug;50(8):2696-702. Epub 2013 May 22. 
• Lemire M, Fillion M, Frenette B, Passos CJ, Guimarães JR, Barbosa F Jr, Mergler D. Selenium from dietary sources and motor functions in the Brazilian Amazon. Neurotoxicology. 2011 Dec;32(6):944-53.
• Miller E, Kaur G, Larsen A, Loh SP, Linderborg K, Weisinger HS, Turchini GM, Cameron-Smith D, Sinclair AJ. A short-term n-3 DPA supplementation study in humans. Eur J Nutr. 2013 Jun 23.
• Portolesi R, Powell BC, Gibson RA. Competition between 24:5n-3 and ALA for Delta 6 desaturase may limit the accumulation of DHA in HepG2 cell membranes. J Lipid Res. 2007 Jul;48(7):1592-8. 
• Virtanen JK, Laukkanen JA, Mursu J, Voutilainen S, Tuomainen TP. Serum Long-Chain n-3 Polyunsaturated Fatty Acids, Mercury, and Risk of Sudden Cardiac Death in Men: A Prospective Population-Based Study. PLoS One. 2013;7(7):e41046.

On Short Notice: Retinoic Acid vs. Lung Cancer / Metabolic Effect of Fats in Cerebral Fluid / Nucleotid Supplements Instead of Icepacks // Ibuprofen & Leaky Gut / Fish Oil Enema & Colitis / Fructose, Glut-5 & Obesity + More!

Image 1 (Coloribus): Unquestionably a great add, but the (Ex-)Marlboro man would be better off with a piece of liver than a carrot ;-)

Just as I promised I am pumping out another set of "short notice" items. To make sure not to be confused with what I have once heard someone call a "pubmed warrior", I did however spike today's episode with three longer items and saved a couple of mini-items for the next week. I hope you enjoy the ride and don't forget to copy "Fatfree" who asked for more in-depth info on TUDCA after reading last Saturday's installment of this series (see "Testosterone - 12% Drop With 75g Glucose? Low T3 Syndrome - Can TUDCA Help?"). If there is more information that would make a longer post worthwhile and I find the topic interesting enough to spent the time on doing the research, I am always willing to comply with wishes like this :-)

Retinoic acid (not beta carotene!) can protect smokers from lung cancer

In a paper that has just been published in the Journal of Food Sciences, Xue et al. report that the epigenetic switches retinoic acid (active, real vitamin A) triggers in cancer cells of lung cells in cigarette-smoke exposed rodents does effectively counter the upregulation of the 120 mostly cell-differentiation and proliferation related genes scientists believe to be a causative factor in the etiology of lung cancer. This is particularly interesting, because supplementation with larger amounts of the vitamin A precursor beta-carotene has been found to pose a serious health risk for smokers. With a passive smoke exposure equivalent to 80 nonfiltered commercial cigarettes the per day it is almost marvelous how effective the 10mg/kg bodyweight of all-trans retinoic acid were.

Figure 1: While all-trans-retinoic acid (left, bottom) appears to have potent anti-lung-cancer effects the β1-apocarotenoids our bodies produce from beta carotene could potentially negate these beneficial effects (see "Anti-Vitamin A Effects of Beta Carotene"); this would also explain why previous research has shown that beta-carotene supplements are potentially hazardous for for smokers (cf. Druesne-Pecollo. 2010)

I guess, the most studious among you will probably already know how the differing effects of vitamin A (real ATRA) and beta carotene come about, right? In my recent blogpost on the "Anti-Vitamin A Effects of Beta Carotene", I did actually provide a mechanistic explanation as the metabolic byproduct that arises from high dose beta carotene supplementation will block the retinoic acid receptor (similar to the way a SERM blocks the estrogen receptor) and thus inhibit the inhibitory effects of real vitamin A on the occurrence and progression of cancerous growth.

Image 2: Helicobacter pylori, ain't the reason you get lung cancer, but smoking will help him to prepare the breeding ground for gastric cancer.

Apropos lung cancer, a study by Koshiol et al. has recently refuted the claim that Helicobacter pylori (H. pylori) infections would increase the risk of lung cancer (Koshiol. 2013). Previous research from the German Center for Research of Ageing, on the other hand, found conclusive evidence that the combination of h. plyori and smoke increases the risk of gastric cancer by more than 600% (Brenner. 2002)! But don't worry, all-trans-retinoic acid can take care of that, as well. At least in the Petri dish, incubation of human gastric cancer cells with ATRA lead to immediate growth arrest (Zhang. 2005)... and did I mention it does the very same thing to pancreatic cancer, breast cancer and leukemia cells?

Implications: Regardless of whether you live with a chainsmoker, work in a bar or are stranded on a lonely island, where your campfire is the only source of smoke in your life, try to get your real vitamin A (=retinol) from fatty animal products and forget about beta carotene supplements (even if you brought some to your lonely island ;-). With fatty fish, a piece of liver every now and then, butter, eggs, etc. and large amounts of green leafy vegetables and a reasonable amount of whole fruits (no juices!) you are guaranteed not to fall short of any of these "vitamins A" (retinol and beta carotene) and the multitude of other potent carotenes that would be missing from your supplements anyway.

Type of fatty acids in cerebral fluid determine metabolic rate

Image 3: Assuming that the fatty acids you eat also float around in your brain peanut oil (1-2.5% C:24) is the worst edible oil for anyone who is concerned about his overnight energy expenditure.

A study that has just been published on PLos ONE provides astonishing insights into how long chain fatty acids (saturated fats) in your cerebral fluid could (we are dealing with observational human data from a metabolic ward study, here) slow down your fat loss or even make you gain weight by decreasing overnight energy expenditure. With correlations in the range of -0.6, lignoceric acid (C24:0, as in peanut oil) and Cerotic acid (C26:0; as in beeswax) are by far the worst offenders, as far as overnight energy expenditure are concerned; and though the design of the study did not allow for any conclusions on the underlying mechanisms, the fatty acid induced suppression of the nocturnal surge in growth hormone could be one potential and at least in my humble opinion not very far-fetched cause for this effect. Interestingly, things look completely different for the plasma levels of these fatty acids, which showed the exact opposite +0.6 correlation with 24h energy expenditure. Other noteworthy results were

• significant correlations of the mono-unsaturated fatty acids palmitoleic and oleic acid in the cerebrospinal fluid with higher rates of fatty acid oxidation (relative to carbs, not total) and 
• significant correlations of the omega-6 fatty acids linoleic (18:2n6), dihomo-g-linolenic acid (20:3n6) and arachidonic acid (20:4n6), the omega-3 fatty acids linolic acid and docosapentaenoic acid (DPA, C22:5n3) and the omega-9 fatty acid mead acid (C20:3n9) with better glucose clearance.

And no, the much-lauded fish-oil, i.e. the EPA and/or DHA content of the cerebrospinal fluid, had no significant effect on glucose tolerance. A result, by the way, which reminds me of another study I came across recently:  In their four day supplementation trial Miller et al. observed vast differences between the incorporation of EPA and DPA (docosapentaenoic acid, the one that did correlate - weaker than the omega-6s, though - with improved glucose tolerance) into plasma and red blood cell lipids subsequent to the oral provision of 8g/day of each to ten healthy women. Their observations and the respective alterations in EPA and DHA in the DPA supplementation group Miller and his colleagues concluded that DPA could serve as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans - exciting stuff and probably something you will read more about, here at the SuppVersity in the future.

Image 4: The data would support the use of MUFA and omega-6 laden olive and high MUFA macadamia oils, if we know how their consumption effects the fatty acid flux in our brains.

Implications: Due to our lack of knowledge about the ultimate determinants of cerebrospinal fluid fatty acid composition it is hard to say if these results do imply that you better focus on MUFAs in view of their beneficial effect on both glucose clearance and respiratory quotient - and still the usefulness of MUFA and omega-6 laden olive oils, which have time and again been shown to produce all sorts of favorable changes in glucose, fat and overall energy metabolism would support the notion that there is a direct or indirect downstream effect of higher intakes of the respective fats, their occurrence in our cerebrospinal fluid and their downstream metabolic effects.

Cooling trained muscles appears do decrease regeneration

Soon to be published in the Journal of Strength and Conditioning Research are the results of a randomized cross-over study into the effects 15 minutes of icing applied 0h, 3h, 24h, 48h and 72h after an intense eccentric arm workout with 6 sets of elbow extension performed at 85% maximum of the voluntary maximal load had on the subjective as well as measurable (inflammatory cytokines, creatine kinase (CK-MB), hemoglobin and oxygenation were assessed) regeneration of 11 young male college baseball players (Tseng. 2013).

Figure 2: Inflammatory cytokines, creatine kinase and visual analgue scale data on subjective perception of fatigue at different timepoints before and after the eccentric arm workout (data adaptedm from Treng. 2013)

As you can see from the data in figure 2 the icing did have a somewhat bizarre effect on the inflammatory and subjective indexes of muscular regeneration. While...

[...] significant change in the levels of IL-1β, IL-8, and IL-1 were observed following the muscle-damaging eccentric exercise in either the control or topical cooling conditions and no differences in these cytokines were found between the control and cooling trials throughout the 72 h observation period (data not shown in figure 2, Tseng. 2013).

The levels of the pro-anabolic cytokine IL-12 (Argile. 2001), TNF-α, and IL-6 were significantly lower 24h after the workout (see figure 2, left; p < 0.05). There were yet no significant differences at other time-points ant both the CK-MB, as well as the fatique score (figure 2, right) suggest that the overall regenerative capacity was compromised by the repeated cooling of the strained musculature.

Image 4: If you use a 41°C hot bath 48h before a workout to "pre-generate", you don't even need to ask yourself whether or not the results of the study at hand conclusively imply that icepacks are detrimental and their use after workouts has to be avoided at all costs.

Although I must admit that this is not a settled case for me, until we understand the unexpected dip in IL-12, TNF-α, and IL-6 after 24h and its relation to the obvious increase in muscle damage (CK) and corresponding fatigue levels, it would appear prudent not to make use of an icepack as your regenerative means of choice.

Instead, I would suggest you follow the example of the young lady on the left and take "pregenerative" measures by taking a 41°C hot bath 48h before a strenuous workout. As you will probably remember from my previous article on the Touchberry study (read full story based on Touchberry. 2013) this will not just keep the damage at bay, but may also help you on your quest to a more muscular physique. And if you want to do your immune system a favor, check out the on very short notice item about RNA + DNA precursor supplementation further down...

On Very Short Notice

• 

  Image 5: Adding ibuprofen on top of exercise will make your gut look like a riddle screen.

  Ibuprofen makes an exercise-induced leaky gut even leakier - The use of NSAIDs such as aspirin and ibuprofen has long been implicated in the etiology of all sorts of gastrointestinal problems ranging from benign gastroinstestinal distress, over gastrointestinal bleading, ulcers etc. to all sorts of cancers. Researchers from the Top Institute Food and Nutrition at the University of Maastricht in the Netherlands have now found that the way by which ibuprofen aggravates the exercise-induced small intestinal injury and induces an even more pronounced gut barrier dysfunction in healthy individuals than exercise alone, may not just contribute to the occurrence of the aforementioned pathologies, but also precipitate to systemic diseases. After all, it opens up the doors to pathogens and toxins, which would otherwise be blocked by an intact intestinal barrier (van Wijck. 2013).
  N-acetyl-L-cystein (NAC) a potent natural anti-inflammatory which has also  been shown to reduce exercise induced inflammation (see "NAC Improves Markers of Oxidative Stress Induced by High Intensity Exercise") and glutamine (in the dos Santos study a HED of "only" 3-5g/day), on the other hand, exert protective effects on the integrity of the intestinal barrier (Sun. 2002; dos Santos. 2010).
• Fish oil enema ameliorates colitis - When administered intra-rectally at a human equivalent dose of  ~13ml, fish oil effectively ameliorated the mucosal damage in experimentally induced ulcerative colitis in rat; flax oil and the corn oil control, on the other hand, did not prevent the increase in colonic weight / /length ratio and the associated histological changes 24h after Aisha Mohamed Dugani, Ahlam Elhelawi and Aisha Edrah had administered 1ml of 4% acetic acid to induce the colic (Mohamed Dugani. 2013). These results stand in line with general colon-protective effects of fish oil, observed in other studies and it's likely that they are a direct consequence of its non-negligible anti-inflammatory effect - which does not change my assessment that healthy physical culturists should not take more than max. 2g of supplemental fish oil per. The evidence supporting any beneficial effects on non-insulin-resistant, non-obese, non-hypertriglyceremic individuals is simply non-existent.

• 

  Image 6: No, this certainly does not look as if the conjugated linolic acid would work in horses as it does in mice ;-)

  Species specific effects of CLA: Horse don't lose weight, either - You will probably remember my recent post on the adipose tissue destroying effects of CLA (cf. "CLA Destroys Body Fat") in rodents, as well as my remarks that - if we discard potential underdosing as a contributing factor - it would appear that the beneficial effects of CLA we see in rodent studies is highly species specific. Now, Headley et al. have published the results of a study that investigated the effects of 0.05% CLA enriched chow on horses. Similar to what we see in humans, the conjugated linoleic acid had no effect on the body composition of the animals. Interestingly though, the mixture of three CLA isomers used in the study (cis-9, trans-11 + trans-10, cis-12 + and trans-9, trans-11; usually we have only the latter two in significant amounts) led to a statistically significant reduction of the potentially pro-inflammatory arachidonic acid in the blood of the horses. This spiked the interest of Headley et al. as it could turn out that this would render CLA (this specific isomer mix, I should say) as an agent that could have beneficial effects on the progression of joint disease, which is - in parts - driven by C20:4 (chemical name for arachidonic acid).
• Towards a better understanding of why fructose is making us fat - Using in-vitro studies and a genetically engineered Glut5 -/- mouse model (these mice lack the glut-5 receptor which is responsible for the uptake of fructose), Li Du and Anthony P. Heaney were able to show that the preferential expression of Glut5 in developing adipocytes and the corresponding adipogenic (=promoting the creating of new fat cells) effects of fructose could well explain why fructose, which can no longer be taken up by mature fat cells, has been shown time and again to be way more fattening than its pro-insulinogenic cousin glucose (Du. 2013). Put simply, you could say: Increased serum levels of fructose require a) the conversion of fructose to triglycerides of glucose in the liver or b) the proliferation of adipose tissue so that the developing new fat cells can take the superfluous fructose up. If you consume too much of so that your liver is already working overtime, it is no wonder that your healthy high-fructose corn-syrup fat-free breakfast cereals are making you fatter and fatter. 

• 

  Figure 3: Effects of incremental treadmill running on selected markers of immune activity before and after 2 weeks of sublingual treadmill running in 38 healthy young men nucleotid supplementation (Ostojic. 2013)

  Supplement with RNA and DNA building blocks protects from immune-suppressive effects of exercise - The effects Sergej M Ostojic and Milos Obrenovic observed in response to a 14-day sublingual nucleotide supplementation regimen were basically what common wisdom tells you, you should see as a result of glutamine supplementation (Ostojic. 2013): The RNA and DNA precursors did not just ameliorated the dreaded immune-suppressive effects of a standardized cardio workout on a treadmill, they effectively boosted natural killer cells count and cytotoxic activity as well as salivary immunoglobulins and lactoferrin (cf. figure 3); so profoundly, though, that I am not 100% sure this is a good thing - at least not for people with auto-immune issues.
• Don't stress yourself if you want to recover as fast as possible! That's the take home message of a recently published study by two researchers from the Nothern Illiniois University and the University of Texas at Austin, who correlated measures of perceived psychological stress with physical data on exercise recovery and found a surprisingly linear relationship between perceived stress, on the one hand, and phyical recovery as measured by maximal isometric force, on the other hand, in 31 undergraduate resistance training students (Stults-Kolehmainen. 2013). So, mark my words: Don't overstress about making everything right (this includes having the optimal workout and nutrition plan and thinking about whether or not you should add in another 0.5g BCAA pre-workout or not), if you don't want to sabotage your training success.

References

• Argilés JM, Meijsing SH, Pallarés-Trujillo J, Guirao X, López-Soriano FJ. Cancer cachexia: a therapeutic approach. Med Res Rev. 2001 Jan;21(1):83-101.
• Brenner H, Arndt V, Bode G, Stegmaier C, Ziegler H, Stümer T. Risk of gastric cancer among smokers infected with Helicobacter pylori. Int J Cancer. 2002 Mar 20;98(3):446-9.
• dos Santos RG, Viana ML, Generoso SV, Arantes RE, Davisson Correia MI, Cardoso VN. Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity in an experimental mouse model. JPEN J Parenter Enteral Nutr. 2010 Jul-Aug;34(4):408-13.
• Druesne-Pecollo N, Latino-Martel P, Norat T, Barrandon E, Bertrais S, Galan P, Hercberg S. Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials. Int J Cancer. 2010 Jul 1;127(1):172-84.
• Du L, Heaney AP. Regulation of Adipose Differentiation by Fructose and GluT5. Mol Endocrinol. 2013 Jul 24.
• Headley S, Coverdale JA, Jenkins TC, Klein CM, Sharp JL, Vernon KL. Dietary supplementation of CLA in horses increases plasma CLA and decreases plasma arachidonic acid, but does not alter body fat. J Anim Sci. 2013 Jul 24.
• Jumpertz R, Guijarro A, Pratley RE, Mason CC, Piomelli , Krakoff J. Associations of Fatty Acids in Cerebrospinal Fluid with Peripheral Glucose Concentrations and Energy Metabolism. PLoS ONE 2013; 7(7): e41503.
• Koshiol J, Flores R, Lam TK, Taylor PR, Weinstein SJ, Virtamo J, Albanes D, Perez-Perez G, Caporaso NE, Blaser MJ. Helicobacter pylori seropositivity and risk of lung cancer. PLoS One. 2013;7(2):e32106.
• Miller E, Kaur G, Larsen A, Loh SP, Linderborg K, Weisinger HS, Turchini GM, Cameron-Smith D, Sinclair AJ. A short-term n-3 DPA supplementation study in humans. Eur J Nutr. 2013 Jun 23.
• Mohamed Dugani A, Elhelawi A, Edrah A. Comparative effect of flaxseed oil and fish oil in acetic acid induced colitis in rats. The Libyan Journal of Pharmacy and Clinical Pharmacology LJPCP. 2013;1.
• Ostojic SM, Obrenovic M. Sublingual nucleotides and immune response to exercise. Journal of the International Society of Sports Nutrition 2013, 9:31. 
• Stults-Kolehmainen MA, Bartholomew JB. Psychological Stress Impairs Short-Term
  Muscular Recovery From Resistance Exercise. Med Sci Sports Exerc. 2013 Jun 8.
• Sun Z, Lasson A, Olanders K, Deng X, Andersson R. Gut barrier permeability, reticuloendothelial system function and protease inhibitor levels following intestinal ischaemia and reperfusion--effects of pretreatment with N-acetyl-L-cysteine and indomethacin.
• Touchberry CD, Gupte AA, Bomhoff GL, Graham ZA, Geiger PC, Gallagher PM. Acute heat stress prior to downhill running may enhance skeletal muscle remodeling. Cell Stress Chaperones. 2013 May 17.
• van Wijck K, Lenaerts K, van Bijnen AA, Boonen B, van Loon LJ, Dejong CH, Buurman WA. Aggravation of Exercise-Induced Intestinal Injury by Ibuprofen in Athletes. Med Sci Sports Exerc. 2013 Jul 6.
• Xue Y, Meadors EP, Wang W, Baybutt RC. Microarray Analysis reveals that Dietary Retinoic Acid Suppresses Cancer Related Gene Expression of the Lungs of Cigarette Smoke-Exposed Rats. J Nutr Food Sci 2013, S2.
• Zhang JP, Chen XY, Li JS. Effects of all-trans-retinoic on human gastric cancer cells BGC-823. J Dig Dis. 2007 Feb;8(1):29-34.