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.

Standard American Diet Has 'Optimal' Fatty Acid Ratio to Induce Diabesity. Plus: Study Shows Doubling Saturated Fats Would Yield More Benefits Than Halving Them

Study confirms: The SAD diet yields 'optimal' results (img. forbes.com)

Since this post is already lengthy enough, I will spare you how saturated fatty acids have long falsely been accused as the sole driving force of the western obesity epidemic and how the tides appear to be slowly yet steadily appear to be turning, as scientists delve deeper and deeper into the interactions of the total fat content in the diet, its fatty acid composition and the interaction of both with the two other macronutrients and their specific forms and get right to the study at hand. A study that appears in the current issue of the Journal of Lipid Science and deals with the first of the aforementioned interactions. The one that focuses on the total fat content and the individual fatty acid make-up of the diet (Enos. 2013).

Fat shoot out: Saturated vs. mono vs. PUFA

As Enos et al. point out, the main purpose of their study was to examine the effects of three high fat diets differing only with respect to the percentage of total calories from saturated fats.

• SFA-6% - contained 6% saturated fats,
• SFA-12% - contained 12% saturated fats, and
• SFA-24% - contained 24% of saturated fats

While the the high fat diets were set to have an identical fat (40% of the energy), carbohydrate (45% of the energy) and protein content, the two control diets were low in total fat (12%/68%/20% of the energy from fat/carbs/protein). They did however likewise differ as far as their fatty acid composition is concerned, with the modified chow mirroring the ratios (!) not the amounts of mono- and polyunsaturated fatty acids of the high fat chow (see figure 1).

Figure 1: Fatty acid composition (left) and their sources (right) that were used in the different diets the rodents were fed for 16 weeks (based on Enos. 2013)

The diets were administered for 16 weeks. Body composition and metabolism (glucose, insulin, triglycerides, LDL-C, HDL-C, total cholesterol) were examined monthly.  Adipose tissue (AT) expression of marker genes for M1 and M2 macrophages and inflammatory mediators (TLR-2, TLR-4, MCP-1, TNF-α, IL-6, IL-10, SOCS1, IFN-γ) was measured and so on and so forth... and the results were... well, not exactly as you may have expected (the latter statement assumes that you expected the SFA to be either the savior or the doom of the human race, depending on which side of the LC/LF divide you are stading).

Figure 2: Body composition (left), adipocyte size (right) and fat pad weight (inset) of the rodents at the end of the study period (Enos. 2013) Values not sharing a common letter (abc) differ significantly over time within the given diet treatment (P≤.05)

If you take closer look at the data in figure 2, there are two things that will probably catch your eye right away. The first 'eye catcher' pertains to the influence of replacing a large amount of the omega-6 fatty acids by monounsaturared fatty acids, as you will find them in olive oil, for example.

• The rodents who received the modified standard chow, with a fatty acid composition identical to the high fat diets (SFA-6%, SFA-12%, SFA-24%) had the exact same body composition as their mates who received the standard chow with its 3.7x higher n6:n3 ratio. The removal of omega-6 fatty did thus not have any beneficial effects on adiposity in the low fat groups.

The second 'eye catcher' is the non-linear increase in adiposity with increasing amounts of saturated fatty acids in the diets. This does not mean that the expected increase in obesity and adipocyte size was totally absent (read the latest "Get Lean & Stay Lean" item for more information about the association of large fat cells and metabolic syndrome), though:

• The mice in the SF-6-24% did all gain significantly more body weight and body fat than their peers on the low fat diets, but there appears to be a turning point, when the saturated fat content exceeds 12%. After all the mice in the SFA-24% group had almost the same body composition as their peers on the SFA-6% diet.

So, what do we make of these 'eye catchers'? The first one, you could argue, shows that "omega 6 overload" is not a problem, as long as you are consuming a low fat diet, in the first place. Even with the major part of those 12.2% of energy your diet provides in form of various fatty acids belonging to the potentially inflammatory omega-6 fatty acids, that's still way too low to do any harm. It does, by the way, yet explain why low fat diets work so well in a society, where most high fat foods the public consumes are laden with omega-6 fatty acids - not an insignificant result, I would say.

The 12%-SF diet, most closely mimics the standard American diet

Apropos public, the second 'eye catcher' is even more telling in term of public health,... wait, I should write sickness. Why? Well, the 12%SFA high fat diet, which supplies ...

• 47% of energy in form of carbohydrates (380g sucrose, 100g maltodextrin, 50g cornstarch per 1kg of diet; identical for all SFA groups),
• 40% of energy in form of fats (of which 12% were saturated fats), and
• 13% of energy in form of protein (from casein),

... mimics, as the researchers point out, "most closely" (Enos. 2013) the standard American diet (SAD). And the result is obvious: Diabesity!

It's a fat balancing act of macro and micro ratios  - complex and far from being understood 

What's intriguing though, is that the adipogenic effects of the diet were ameliorated, when the SFA content was further increased and the diet contained 68.6g of lard per kg chow instead of just 35.4g and 96.7g of coconut oil instead of just 30g. Since this increase in SFA was at the expense of both mono- and omega-6 fatty acids, you could of course also argue that replacing at least the latter of the two with SFAs must be healthy. Unfortunately, even a brief glance back at figure 2 reveals that this is not necessarily correct. After all, the SFA-6% group was still better off than the SFA-24% group, although they had the highest amounts of oleic and omega-6 fatty acids in the diet.

By now you should actually have realized that this is once more a difficult balancing act. Where different baseline intakes of dietary fat and carbohydrates (total) are pair of setscrews and the individiual fatty acid composition of the diet is another one. And the way these setscrews are set will not just influence the body composition:

Figure 3: Serum IL-6, MCP-1, adiponectin and leptin levels, TNF-alpha mRNA expression in the adipose tissue (left), adipose tissue sample form the rodents receiving standard chow, the SFA-12% and the SFA-24% diet (Enos. 2013). The fat cells of the SFA-6% animals looked similar to those on the SFA-6% diets.

Based on the body composition data presented in figure 2 the marked increases in serum leptin and TNF-alpha mRNA expression in the adipose tissue of the rodents in figure 3 (left) should be about as unsurprising as the fact that the adipocytes of the SFA-12% group show the greatest macrophage infiltration and subsequent necrotic tissue.

If anything is surprising, it is the non-significance of the peak in IL-6 in the SFA-24% group (this was due to a very high standard deviation) and the fact that the serum level of MCP-1 a marker of increased macrophage activity was not elevated, while the adipose tissue mRNA expression was significantly higher (5-8x) in all SFA groups compared to both of the control diets. In the end this is yet only another clear sign that far more processes than we have previously thought happen locally and do not depend on circulating and thus endocrine signaling molecules.

Figure 4: Blood glucose and insulin levels of the mice over the course of the study period (Enos. 2013)

If you take the data from figure 4 into account as well, you will certainly agree with the statement Enos. et al. make pertaining to the negative effects of the SFA-12% diet, which is - just to remind you - the mirror image of the standard American diet:

"The 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity (absolute fat mass), macrophage infiltration, and IR [insulin resistance]." (Enos. 2013)

Figure 5: Total  cholesterol (TC, top) and LDL-C to HDL-C (bottom) ratios (Enos. 2013)

And I guess it would actually be about time to get to the bottom line, here, if it was not for the sentence that follows this assertion:

"Although the 24%-SF diet increased adiposity and produced IR, it did not significantly increase macrophage infiltration, it led to a lesser degree of AT inflammation, and it did not raise the TC/HDL-C ratio." (Enos. 2013)

Yep, you are reading right, as the data in figure 5 shows the total to HDL ratio of the SFA-24% group, which were those rodents who consumed the largest amount of "bad" saturated fat, was virtually identical to the one of the rodents on the standard and the modified standard chow and significantly lower than in those rodents who 'lived the American way of life' (SFA-12%). A similar trend was seen in the LDL:HDL radio and the triglyceride levels.

Bottom line: So, does that mean that we would just have to fry our potato chips in lard and all will be good? Not really, no. If we keep munching tons of plain sugar, even a saturated fat only diet is not going to save us from doom (I suspect there will be another inflection point at levels which exceed 50% SFA, anyway). What the study results do yet clearly implicate is that the macronutritent and fatty acid composition of the standard American diet is downright conspicuously obesogenic, pro-diabetic, inflammatory.

While the macronutrient ratio (high carb + high fat) appears to set the body into fat storage mode, the individual ratios of the fatty acids determine the efficacy of body fat storage, the negative effects on blood glucose management, and the degree of adipose tissue inflammation - and the standard American diet excels in all these disciplines.

As far as the saturated fats go (I wonder if it also plays a role that one of the main sources was coconut oil), the study suggests that you can achieve ameliorations of adiposity on both sides of the 'obesogenic optimum' of 12% saturated fats. If you take a last look at the data in figure 4, you will yet have to concede (or triumph?) that eating more not less saturated fat and thus frying your potatoes in lard, appears to be the more promising modification you could make, if the saturated fat content of the diet was your only set screw. Feels good to know it isn't right?

References:

• Enos RT, Davis JM, Velazquez KT, McClellan JL, Day SD, Carnevale KA, Murphy EA. Influence of Dietary Saturated Fat Content on Adiposity, Macrophage Behavior, Inflammation, and Metabolism: Composition Matters. J Lipid Res. 2013 Oct 28.

Adelfo Cerame: How to Manage Training & Nutrition Around a Busy Life. Plus: Science Round Up Sneak Preview

If there is a one body part, where Adelfo has really made awesome progress in the last months, it's his back - by the wa that's a different "back" than in "training back-to-back" of which you'll read in this installment of his now biweekly posts ;-)

It probably sounds strange, but last week I have really been missing Adelfo's update. Not because it's more work for me to write yet another blogpost... ah, whatever. There's another one today and there will be the next one in two weeks time from now :-)

Before we are getting to more details on how Adelfo's contest prep and the rest of his increasingly busy (as you will see in a very positive kind of way) life, let's get to the sneak peak on today's SuppVersity Science Round Up. I felt the show last week was awesome and must pad my own shoulder for having the ingenious idea to simply pack those news that did not fit in, as well as "bonus material", into a written follow up on Friday - a new segment if you will, the SuppVersity Science Round-Up Seconds.

SuppVersity Science Round Up: Sneak Preview

Long story short, if you are interested in any of the following and Carl and I don't discuss them today on The SuppVersity Science Round Up live on Super Human Radio at 1PM EST (for Europeans that's 19:00 GMT+1), don't worry, they will be in the "Seconds" tomorrows... so, let's see what's the most likely to make it exclusively to the live show and the podcast that's published ~1-2h later and will automatically appear in the side-bar under "Physical Culture for Your Ears":

• The rewarding effects of exercise and how they will calm your greed
• Omega-3, telomere length, endocannabinoids and how enzymes link them all
• Premature ejaculation and how only two hormones seem to make a difference
• Personalized prostate cancer vaccine and Harvard scientists build it from scratch
• Supps vs. medications and how healthy supps and necessary drugs form deadly duos

Ther is more, but  you know an hour is short and I am not a friend of rushing through a topic, so I'll stick to those, because even if we don't get off on a tangent (which is usually an interesting one), this is going to be a tight schedule. That said, I have taken up already way too much room of this, Adelfo's blogpost. So let's get him back on the grind!

Adelfo Cerame: Back to the grind and busier than ever

These past months I have been blessed with great opportunities to further my ambitions in chasing a career in the fitness and health industry and being able to do what I love and have a passion for. As of late, life for me has been very busy; and productivity in achieving my future goals has increased 10-fold. With my final three months of school approaching before graduation, and working two part-time jobs, I still have to find a way to juggle in my training and nutrition regimen while still being efficient.

How I  manage my training around the mandatories of life

If your are among the newbies here at the SuppVersity you may want to go back on read up on Adelfo's history, and how "A Terrible Accident Paved His Way to Competitive Bodybuilding"

With my current hypertrophy/strength training split + the incorporation of using an RPE scale, and given that my daily workouts are basically full body workouts but with a dominant day of either pulls or push movements. I would have to say that my workouts during my training days are pretty dense. I rest in-between workout days. This gives me four workouts/week, which makes it easy for me to adjust my schedule around my training hours or vice versa.

Life sometimes demands for last minute tweaks, and it requires sure instincts to make that work for you, can't work out in the morning as planned? Fine go in the evening hours, but don't forget to tweak your feeding window appropriately...

With my work schedule being all over the place, I have to plan my workouts on the fly nowadays. I still have a predetermined plan of attack but I also have to be able to adjust on the fly while at the same time not hindering my productivity. So there are times when I train in the morning, at night, and sometimes I even have to split my workouts because I don’t have enough time to finish my workout so I would have to finish the other half later. There are also times when I’m training back-to-back days training the same body parts because that’s the only time I can squeeze it in.

At first I feared that it would be counter productive to train back-to-back days training the same body parts, but coach Alberto said it would be fine in the beginning stages of my prep but once I started getting leaner and dipping into the lower body fat percentile, I would take the rest as needed whether it be one or two days.

And I’m not doing it all the time, just when my work and school schedules are off alignment with my predetermined plan of attack. Also with the whole issue of training back-to-back days; I’ve read and heard that Olympic power lifters basically train the same movements and muscles on a day-to-day basis to practice their craft, and it doesn’t seem like it hinders their progress? Allegedly, I’m not an Olympic power lifter and training at a different cadence and volume, but I am not training like that everyday... anyway, just sayin… I don’t think there would be a big issue training the same body parts back-to-back days once in a while. And if it is, you will be the first to know, after all you will see me stagnate (assuming you keep following this series)

How I manage my nutritional regimen around the mandatories of life 

Actually, one of the beauties of intermittent fasting is that there is not much to manage. Granted, my schedule has become busier, but overall this had very little effect on my nutritional regimen or routine. I’m still able to maintain my IF – 16/8 protocol, and to be honest it actually works very well with my schedule since I’m always on the go.

My tricks to nourish myself appropriately while I am on the go:

• I make sure to stock the bare essentials in my car that I need to hit my macros – These foods don’t require cooking, and have a prep time of less than 3-5 minutes; to me the simplest and most convenient on the go food sources for (A) Protein = Whey protein, and beef jerky (B) Carbohydrates = Bananas, rice cakes, RAW honey and (C) Fats = Nut butters
• I have a space in my trunk where I have a cooler and a box to put my foods in.
• I also keep extra supplements in my car (Whey, creatine, BCAA’s..)
• I always keep a gym bag or a spare gym bag with all my equipment and workout clothes – I always want to have that ready at all times.
• I keep a digital food scale in my car so I can weigh out my foods – It’s a bit weird but you gotta do what you gotta do son!
• And last, I have a myfitnesspal.com-app on my smart phone, so I can log my foods and keep track of my macros wherever I’m at.

Basically the only adjustments that I have to make once in a while is training fasted when I train in the morning (well I have bcaa’s + Creatine… so maybe semi fasted), but I have not noticed any issues with it so far. 

The one thing I have noticed too though is that I haven’t been consistently hitting my fiber goals and eating my fruits and veggies. There are days where I’m just drinking my foods from protein shakes and just get 1 whole food meal… I still get in my minimum of 1 serving/ day of fruits and veggies, but not enough for my liking,. So I remembered one of Adel's favorite sentences:

"Supplements are called 'supplements', because you take them to supplement your diet with all the stuff you would otherwise be lacking." 

 I have taken that to heart and stopped taking all multivitamins and other supplements, when I have more time to prepare my meals. And so I am now that I am missing out on some of the vites and lack fiber in my diet and have begun to take a basic multivitamins and fiber supplements from time to time. Bananas, rice cakes, and nut butters, like almond or peanut butter have also become pretty good companions of mine when I need some on-the-go carbs and fats to go with my protein shake. They’re easy to just store in the back of your trunk and always accessible to me.

My regimen ain't yours, but still...

... despite the fact that we are all different and no single optimal diet and training regimen exists, I hope there may be one or another thing in my regimen you think could be useful... even if it's just that you give up the unwarranted fear of the negative consequences of training back-to-back once in a while ;-)

Have a nice week and feel free to leave me comments, those of you who made use of this opportunity in the past already will know that I am answering all of them -- and did I mention that I actually enjoy the feedback?

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.

The European Horse Meat Scandal - Looking Beyond the Hysteria: Why "Horse-Powered" Lasagna Would Actually be Nutritionally Superior to Its "Beefed-Up" Counterpart

Lots of good meats on Fury from the slaughterhouse ;-)

I am not sure if all of the US and other international students of the SuppVersity have already gotten wind of the huge "scandal" *rofl* about horse meat in convenient foods. In case you ain't no clue what I am talking about, here is the gist: About a week ago the first reports surfaced that some of the junk... ah, I mean instant meals that are sold by the largest supermarket chains in Europe and produced by such "reputable" companies as Nestlé and Co. are "adulterated" with horse meat (if you want to, you can read up on the whole story in the online version of the NY Times; read more).

Actually things started out with frozen Lasagna and now horse meat appears to be in everything the average convenient food lover packs into his shopping basket. Now, frozen lasagna (unless self-prepared) is nothing I would expect the average SuppVersity reader to consume on a regular basis, anyway. And the mislabeling of the products alone would certainly not qualify as being "SuppVersity newsworthy", either. The fact that it may be a smart move of yours to actually buy horse-meat lasagna (obviously not the one that was made with the meat of potentially sick animals) instead of regular one is however exactly the kind of stuff you read about here at the SuppVersity - and I would venture the guess only at the SuppVersity.

"Horse meat? You're kiddin' right?"

If we disregard the argument that horses are "amiable animals" that are "not supposed to be eaten" that's brought forward by many of the costumers as their main rationale why they would not buy horse-meat lasagna or a "Mac Fury" (would certainly be a major advantage over the other "Mac's" you are served at everyone's favorite fastfood chain ;-), there are actually no convincing arguments against the consumption of horse meat.

There is another study, unfortunately in Russian that reports 54% reduction in excess body weight in overweight individuals, whose diets contained obviously significant (yet in the abstract undisclosed) amounts of horse meat, of which the scientists write that it is "a product that possesses lipotropic and choleretic properties" and was the main reason for the "markedly" reduction in body weight, the participants experienced. Moreover, the latter went hand in hand with "a considerable improvement of liver function" (Kadyrova. 1984). Without access to the full-text, I am yet unable to say anything but "interesting" about this study... although, I guess I may add that it is not just interesting, but intriguing that these two were the only horse meat based dietary interventions I could come up with.

That being said, it's certainly no coincidence that the editors of the International Journal of Food Sciences and Nutition decided to finally include the 2013 paper by Chritian Del Bo et al. that has hitherto only been available as an ePub in the March 2013 issue of this monthly Journal. In the said study, the researchers from the Dipartimento di Scienze per gli Alimenti, la Nutrizione e l'Ambiente (that's what I call a well-sounding name ;-) at the University of Milano investigated the "long-term" (=90 days) effects of regular horse meat (2x 175g per week) consumption on the health of 26 of the 52 healthy volunteers who participated in their study and compared them to the 26 participants who were told to abstain from horse-meat for the full three months study period. The results were absolutely unequivocal: Horse meat, as red and culturally depreciated as it may be let to..

• significant reductions in serum levels of total (-6.2%) and low-density lipoprotein cholesterol (LDL; -9.1%) and transferrin levels (- 4.6%), as well as
• increases in total omega-3 content /+7.8%), omega-3s (+8%) and docosahexeanoic acid (DHA; +11%) in the red blood cells of the subjects (p < 0.005 for all)

As exciting as these observations may sound, the study design makes it difficult to say whether they were a result of replacing horse-meat for other meats or simply eating meat at all (I know you that common wisdom tells us that red meat kills, but you've heard me talk about the fallacy of this assumption on one of the last installments of the Science Round Up).

Aside from the common (and flawed) wisdom about the ill health-effects of meat eating aside, there is another important and obviously way more convincing argument for the former explanation (replacement effects), which pertains to the omega-6 to omega-3 ratio in horse-meat.

Table 1: Omega-6 (N6) to omega-3 (N3) ratio of selected foods (extended version of Bourre. 2005)

With an omega-6 to omega-3 ratio of 0.6 and thus 1 gram of omega-6 fatty acids per 1.7 grams of omega-3s, horse meat is almost on par with farmed salmon (see "Making the Right Fish Choices") and far superior to grass-fed beef, which contains 2 grams of omega-6 fatty acids for every single gram of omega-3s (n-6/n-3 ratio of 2.29; see previous SuppVersity post).

"Hold on! Where is the downside? Where the "on the other hands?"

With 100g of horse meat offering 21g of quality protein, 5g fat (approx. 1g saturated fat, 2g monounsaturated fat and 1g PUFAs) and obviously zero grams of carbohydrates, the ideal protein source, but wait: All this does in fact sound a little "too good too be true" and there are in fact a couple of "on the other hands" attached:

• The Lance-Armstrong factor: As already mentioned before, there is currently a large concern about medicine residues in the horse meat that was added to the instant meals over here in Europe. Yet despite the fact that you can certainly argue that there is a certain chance you would be eating a former race-horse, which collapsed from an overdose of performance enhancing drugs, regular horse meat is as tightly controlled as all other meats and your chances to consume consume any sort of medication are thus not higher lower than with other meats, as long as you don't buy them on the gray market in Romania (where the horse meat in the scandal is supposed to come from) or China ;-)

• 

  I guess you may have heared about toxoplasma gondii being transfered from rodents to cat and accidentally to humans, but do you also know that infected men have higher testosterone levels? No? Well, in the end this is not a recommended way to up your testosterone production, anyway (lean more)

  The nasty bugs factor: Another commonly heard argument against eating horse-meat is based on some horror stories about people dying from bacterial infections after consuming old, imported and improperly stored (the scaremongerish reports obviously don't mention that) raw horse-meat (Gill 2005). This is obviously another non-horse-specific problem and can be easily avoided by buying your meats from the right sources and heating them to temperatures >67°C. The heat will also take care of any Toxoplasma gondii contaminations and the larvae of Trichinella. Both parasites are often named in the same breath as "horse meat", despite the fact that they are not horse-specific and have almost exclusively been found in meats imported from overseas (Pozio. 2001; Pomares. 2011).

• The polar-bear factor: Just as in the case of the polar bears this does not affect the meat of the horses, but their organs. Depending on the soil on which the horses were housed, their livers and kidneys may contained high amounts of heavy metals (cadmium, Gill. 2005; lead, Kosla. 1989) and are thus not recommended for human consumption unless prior testing was done. 

So, basically this leaves us with only one "on the other hand": The "I don't want to eat Black Beatuy or Fury" Factor. But let's face it: Who of the bacon lovers would say he'd like a piece of Babe?

---

You have been eating dozens of "Babes" and now you refuse to eat the much healthier Black Beauty?

Bottom line: Unless your horse meat is imported from questionable sources, the only valid argument why you shouldn't eat horse meat, and maybe even prefer it over beef, let alone pork, are your own scruples culturally rooted scrouples about eating such a "noble" animal as a horse.

And by the way, when it's cooked its pretty hard to distinguish from beef, anyway. Only when you eat it raw (which is something I don't recommend) you may be able to recognize the slight tinge of sweetness that's a result of the 7x higher glycogen content of horse vs. beef meat.

 
References:

• Bò CD, Simonetti P, Gardana C, Riso P, Lucchini G, Ciappellano S. Horse meat consumption affects iron status, lipid profile and fatty acid composition of red blood cells in healthy volunteers. Int J Food Sci Nutr. 2013 Mar;64(2):147-54.
• Bourre, JM. Where To Find Omega-3 Fatty Acids And How Feeding Animals With Diet Enriched In Omega-3 Fatty Acids To Increase Nutritional Value Of Derived Products For Human : What Is Actually Useful. The Journal of Nutrition, Health & Aging. 2005; 9(4): 232-242.
• Gill CO. Safety and storage stability of horse meat for human consumption. Meat Sci. 2005 Nov;71(3):506-13.
• Kadyrova RKh, Salkhanov BA, Shakieva RA. [Effect of diet therapy using horse meat on liver function of patients with metabolic-alimentary obesity]. Vopr Pitan. 1984 May-Jun;(3):22-7.
• Kośla T, Anke M, Grün M. The lead status of horses from central Europe depending on breed, sex, age and living area. Arch Tierernahr. 1989 Jul;39(7):667-74. 
• Pomares C, Ajzenberg D, Bornard L, Bernardin G, Hasseine L, Darde ML, Marty P. Toxoplasmosis and horse meat, France. Emerg Infect Dis. 2011 Jul;17(7):1327-8.
• Pozio E, Tamburrini A, La Rosa G. Horse trichinellosis, an unresolved puzzle. Parasite. 2001 Jun;8(2 Suppl):S263-5.
• Wise J. "Bute" in horse meat presents very low risk to health, says England's chief medical officer. BMJ. 2013 Feb 15;346:f1066.

Leaning Out on a Bulk? Approx. 6g of Phospholipid(!)-Bound DHA + EPA Per Day Could Make That Possible. Rodent Study Reveals Profound Difference to "Regular Fish Oil"

Can phospholipid-bound N-3s as in krill ward off the fat gain on a bulk?

Your daily visits, comments, feedback, criticism and obviously commendations are not only what makes the hours of work I invest into this blog worthwhile, they are also a constant source of "inspiration" and, as the latest post by Roy Nelson on the SuppVersity Facebook Wall goes to show you, oftentimes point me towards the most interesting stuff. In that, it does not really matter that Roy's question was more or less unrelated to what I personally found absolutely newsworthy in the study he referenced, a study which deals with fish oil supplementation and its *yawn* anti-inflammatory effects.

You learn from me, I learn from you

Now, I guess some of you are similarly fed up with those rodent studies like I am, but bear with me folks, Roy did in fact shoot the bulls-eye with this one (not sure if you realized that Roy, but you did ;-) After all, there was a certain twist to this study. A twist you have actually read about on the suppversity roughly 7 month ago, in a post with the suggestive title "Phospholipid or Triglyceride? What's in Your Fish Oil Caps? Only Phospholipid Based DHA+EPA Reduces Fat Cell Growth & Elevated Insulin Levels Despite Obesogenic Diet" (read more). Both studies, the one at hand, which was published only a couple of days ago in Nutrition & Metabolism, as well as the "old" study by Rossmeisel et al. (read up on the results), dealt with the difference between the "real-rodent-world" differences between triglyceride and phospholipid based n3-PUFAs.

Why are you talking about "n-3 PUFAs" and not simply about fish oil? There are actually two reasons, I am trying to avoid the term "fish oil" in this context. Firstly, real fish has both, triglycerides which make up >90% of the fat in fatty fish like salmon & co. And secondly, the way fish oil supplements are produced usually removes the last phospholipid fractions leaving you with nothing but the triglycerides (another reason to stick to fish as an animal, instead of fish as a gelatine cap ;-)

Rossmeisel et al. have already been able to show that the phospholipid-bound n-3 PUFAs (DHA and EPA) posses physiological effects the cheap triglycerides don't have to offer: They decrease the size of the fat cells and thus provide a structural advantage, the common triglyceride-bound forms of DHA and EPA do not have to offer.

Why is a smaller adipocyte size significant?

Remember the post on choline as part of a weight loss stack (read more)? Guess what: Choline is also part of most phospholipids.

I have been dabbling with adipocyte sizes in previous posts and freely admit that this is a too complex matter to actually support the statement that "small adipocytes are best" (learn more in previous posts).

In a hypercaloric diet scenario, as the one in the study at hand, a  decreased adipocyte size may yet well be considered the structural foundation of reduced baseline inflammation. after all, the size or you could as well say the filling level o the fat cells is directly associated with the amounts of pro-inflammatory cytokines they release (Skurk. 2007).

For those of you who are in fact dabbling with high levels of fat-induced inflammation (these are often the skinny fat guys and girls), this alone would therefore warrant the investment in Krill instead of fish oil, if you can't or don't want to get your dietary phospholipids from fresh fish. The new findings the study by Manar Awada and his (or her?) colleagues from the CarMeN Laboratory in Lyon, France, brings to the table are yet probably a more convincing argument for the majority of physical culturists:

Phospholipid-base N3-PUFAs reduce will cut body fat even on a HFD diet

Yep, that's right. If the results of the Awada study translate 1:1 from you rodents to physical culturists, you could in fact up your caloric intake by 50% and still lose 14% body fat compared to following a "species-appropiate diet" (in the case of a rodent that's obviously a high carb diet, with a macronutrient ratio of 19.1% protein, 57.6 carbohydrates and12.8% fat in it).

Figure 1: Energy intake and body composition (left) and lipid, glucose, insulin and leptin levels (right); data expressed relative to values from the regular low-fat chow group (Awada. 2013)

Now the data in figure 1 and the notion that you could cut body fat on a bulk certainly sounds too good to be true and to be honest, I have my doubts that someone whose following all the nutritional advice you get on the SuppVersity on an almost daily basis will see identical "real-human-world" results (specifically if your diet already contents phospholipid bound N3-PUFAs, which it will if you follow my advice to have fish once or twice a week). But let's be honest, if the consumption of phospholipid bound DHA and EPA at a dosage of 0.08g/kg body weight did nothing but blunt the almost inevitable fat gain on an intense (+50% increase in energy intake) "bulk", that would be awesome - wouldn't it?

What are the underlying mechanisms, here?

Krill protein offers non-negligible health benefits, as well (learn more).

I know many of you mainly interested in the practical implications, but especially, when we are dealing with data from rodent studies, we have to understand how a supplement works, in order to tell something about the probability that it will work in humans as well.

Against that background, it's well-worth to take a final look at those cellular parameters that may provide some clues on what it is that makes the phospholipid forms of DHA and EPA so superior compared to their conventional triglyceride counterparts.

Aside from a highly more pronounced increase in intra-cellular vitamin E (2.8x higher than HFD alone and 1.5x higher than HFD + triglyceride-bound omega-3s), there were yet unfortunately no statistically significant inter-group differences. Even in conjunction with the (probably related) yet statistically non-significant difference in markers of lipid peroxidation (4HHE 104, 89, 128nM and 4HNE 13, 6, 9nM in high fat, high fat + PL and high fat + TG, respectively), this is simply not enough to gain insight into the underlying mechanisms which lead to these highly desirable anti-obesity effects. So that we will, for better or worse, have to contend ourselves with the scientists' own conclusion that "further research is required to better understand the mechanism of action of PL carrier".

Figure 2: The PL N-3 content (g/100g dry mass) of fish is very heat stable compared to the triglyceride fraction of which are partly (baking) or totally (frying) lost when you process the raw fillets (Mai. 1978). So even if your fish has a relatively low PL content, that will at least remain where it is supposed to be ;-)

Bottom line: Without knowing the underyling mechanism and in the absence of respective human data, I am honestly hesitant to suggest you go and buy tons of krill oil supplements. After all, the human equivalent dosage of the amount of phospholipid bound DHA+EPA that was used in the study at hand amounts to ~6g per day. So even if found a product that's 100% phospholipid, 0% triglyceride you would have to take ~30 1g caps of regular krill oil which usually have ~200mg of DHA and EPA in them.

So unless you happen to have a cheap source of the purified omega-3 phospholipids the scientists used in their study, it will probably be more prudent to wait for the third SuppVersity post on this matter and invest the buckloads of money this will save you into fresh fish fillets. 

References:

• Awada M, Meynier A, Soulage CO, Hadji L, Géloën A, Viau M, Ribourg L, Benoit B, Debard C, Guichardant M, Lagarde M, Genot C, Michalski MC. n-3 PUFA added to high-fat diets affect differently adiposity and inflammation when carried by phospholipids or triacylglycerols in mice. Nutr Metab (Lond). 2013 Feb 15;10(1):23.
• Mai J, Shimp J, Weihrauch J, Kinsella JE. Lipids Of Fish Fillets: Changes Following Cooking By Different Methods. Journal Of Food Science. 1978; 43: 1669–1674.
• Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007 Mar;92(3):1023-33.

Making the Right Fish Choices: Fatty Acid Contents of 33 Different Fish Species. Plus: What Are the Implications?

Pollachius virens (Photo: Tino Strauss) is king, when it comes to the n:3/n:6 ratio, but with <1% of fat you will still be hard pressed to get tons of omega-3s from eating pollock... but is more really better, let alone necessary?

I have already broached the issue of the differences in the fatty acid composition of fish - even those of the same species - in past articles such as the one(s) on fish as a potential source of mercury in your diet (read more). When I saw the recent paper by Claudia Strobel, Gerhard Jahreis and Katrin Kuhnt in Lipids in Health and Disease, I thought that it was about time to supply you with some real data on the actual n:3/n:6 ratio of different fish and its implications for the purported health benefits and anti-obesity effects of regular fish intake. Is there a "super fish" or is it as so often a matter of "mixing and matching" to achieve the right balance?

Fish? Of course, I have fish & chips or fish sticks every other day!

I guess I don't have to tell you that both the fish part of "fish and chips", as well as the "healthy" fish sticks that are pretty popular at least among German kids, should actually be sold at the bakery, right? I mean the ratio of the bread crumb coating to the pressed fish fillets inside, is hilarious and in view of the fact that these products are 'pre-fried' with cheap vegetable oil before they end up in the freezer cabinets of supermarkets all around the world, you cannot avoid the increased (partially oxidized) omega-6 intake, even if don't (as most people do) fry them at home.

So, if the fast-food version of "fish" is not an option to gear your polyunsaturated fatty acid ratio more towards the n-3 side of things, which fish shall you go for? Well, according to the data the scientists from the Friedrich Schiller University in Jena, Germany, collected Pollachius virens is the n3:n6 king among the seven most frequently consumed fish species, which are herring, tuna, pollock, alaska pollock, salmon, rainbow trout and iridescent shark (at least according to Strobel, 2013).

Figure 1: Content of EPA & DHA, other omega-3 and the sum of omega-6 fatty acids in percent of total fat of the 33 tested species in the study; ordered according to n3:n6 ratio, fish with the highest n3:n:6-ratios on the left; note: the anchovies and sardines were in a tin with oil and while they were drained before the analysis this will have decreased the n-3:n-6 ratio (data calculated based on Strobel. 2013)

On the other hand, the total fat content of pollock (<1%) is so low that you will be hard pressed eating enough of it to elicit any significant health effects. As far as the most frequently consumed fish species go, this does bring us back to our good old friend, the salmon.

Figure 2: Comparison of fatty acid content in g/100g of wild and farmed salmon (left) and respective omega-3 to omega-6 ratios (right; based on Strobel. 2013)

Unfortunately "salmon" does not equal salmon, these days. The dripping orange stuff you can buy for a few bucks (the orange color is artificially added to the feed by the way) at every supermarket, for example, is farmed salmon and contains only 2-3x more omega-3 fatty acids than omega-6s. The reddish, lean cuts of wild salmon on the other hand, have a 12-13x higher relative omega-3 content and in fact almost no omega-6 fatty acids (0.05g / 100g). With 0.53g /100g omega-3 fatty acids, wild salmon is yet just like pollock not the "bulk" source of omega-3 fatty acids you would be looking for, if you fell for the stupid idea that you could undo the damage you are doing by eating tons of (oftentimes oxidized) omega-6 fatty acids by simply throwing an even greater amount of omega-3s into the equation.

So what do we make of all that information?

The very latest on the effects of fish consumption on body weight comes from a study in the latest issue of the British Journal of Nutrition and shows that there is no effect of higher intakes of total, lean or fatty fish on 5-year risk of becoming obese in the 344,757 male and female participants of the European Prospective Investigation into Cancer and Nutrition (Jakobsen. 2013). Now, this does not exclude the existence of non-body weight related benefits, but it certainly puts the myth of the "anti-obesity" effect of fatty fish into perspective. After all, every 10g of additional high fat fish in the diets of the female study participants was associated with a 5x more pronounced increase in body weight than an equal amount of low fat fish. The general trend towards increasing BMIs was yet countered by none of the two.

In view of the fact that we are suffering from a relative deficiency in omega-3 fatty acids, only (relative to the exubarant amount of omega-6 fatty acids the average Westerner consumes on a daily basis), I see the data presented in this post not as a "shopping guide", but rather as a means to conduct a reality check of how realistic it really is that someone who follows a no fast- and convenient-food diet and keeps a non-neurotic eye on his overall n-6 intake will benefit from omega-3 intakes in the multiple gram range.

Specifically when it comes to supplementation, previous trials such as Filaire et al. did in fact find increases in oxidative stress in perfectly healthy athletes (judo) in response to 6 weeks on 600mg EPA + 400mg DHA per day (Filaire. 2010). If you also take into consideration that these negative effects on lipid oxidation were not ameliorated by higher alpha-tocopherol (vitamin E) levels, the message this and other studies are sending is clear: The putative increase in omega-3 requirements is a result of an abnormally high intake of omega-6 fatty acids.

The easiest way to escape any negative effects while still reaping the benefits therefore is to reduce (not totally avoid!) the intake of omega-6 fats (specifically from processed foods) - full stop! If you do that by incorporating a large variety of whole foods into your diet and include grass-fed beef, dairy from pastured cows and, obviously, fish on a regular basis, you won't have to increase your intake of omega-3 fatty acids by picking the orange colored, disgustingly tasting, fat dripping farmed salmon from the super market over its delicious red wild cousin, just because it has 4.5x more omega-3 fatty acids.

Bottom line: It's food quality and fatty acid ratios that make the difference; not the absolute numbers of allegedly good and bad fats, carbs and whatever else has recently fallen victim to the over-generalization that appears to be necessary to render dietary advice suitable for the masses. If there is any one thing that's to blame for the health crisis these days, it's this kind of black-and-white thinking that's behind the overgeneralized and faulty "expert advice" which is by no means propagated exclusively via supposedly unreliable sources on the Internet.

References:

• Filaire E, Massart A, Portier H, Rouveix M, Rosado F, Bage AS, Gobert M, Durand D. Effect of 6 Weeks of n-3 fatty-acid supplementation on oxidative stress in Judo athletes. Int J Sport Nutr Exerc Metab. 2010 Dec;20(6):496-506.
• Jakobsen MU, Dethlefsen C, Due KM, May AM, Romaguera D, Vergnaud AC, Norat T, Sørensen TI, Halkjær J, Tjønneland A, Boutron-Ruault MC, Clavel-Chapelon F, Fagherazzi G, Teucher B, Kühn T, Bergmann MM, Boeing H, Naska A, Orfanos P, Trichopoulou A, Palli D, Santucci De Magistris M, Sieri S, Bueno-de-Mesquita HB, van der A DL, Engeset D, Hjartåker A, Rodríguez L, Agudo A, Molina-Montes E, Huerta JM, Barricarte A, Amiano P, Manjer J, Wirfält E, Hallmans G, Johansson I, Khaw KT, Wareham NJ, Key TJ, Chajès V, Slimani N, Riboli E, Peeters PH, Overvad K. Fish consumption and subsequent change in body weight in European women and men. Br J Nutr. 2013 Jan;109(2):353-62.
• Strobel C, Jahreis G, Kuhnt K. Survey of n-3 and n-6 polyunsaturated fatty acids in fish and fish products. Lipids Health Dis. 2013 Oct 30;11:144.