Farmed vs. Wild-Caught: Pollutants and A Low Omega-3/6 Ratio - Is Wild Caught Fish Always the Better Choice? Plus: Krill, Fish Oil, or Whole Fish - What's Best for Your Health?

Wild caught or farmed? If you google it, it appears to be as if eating farmed  fish could be worse than eating no fish at all, but is this actually true?

Farmed fish is the ugly duckling in the "superfood" family. It is - at least that's what you'll read on the Internet - low in omega-3s, full of "bad" omega-6 fatty acids and laden with all sorts of pesticides. But wild caught fish is expensive and if we all ate it day in and day out not exactly eco-friendly, right?

In today's SuppVersity special parts of which you may have recently seen pop up for a few hours in interview form over at www.fighterdiet.com, before Pauline Nordin and I decided that due to its length and complexity it was rather an article than an interview and should thus be published as such, I am going to tackle the issue of "farmed vs. wild-caught" and "fish vs. fish oil" from all possible angles.

Do not underestimate fish as a protein source - fish is more than just omega-3!

Salmon Better Than Whey?

Cod protein for recovery

Krill = Super Protein?

High EAA protein for fat loss

Fast vs. slow protein

5x More Than FDA Allows

I would like to start my elaborations with the results of a recent paper by Nichols et al. (2014). A paper, in which the scientists investigate whether the existing differences of the fatty acid profiles from farm-raised vs. wild-caught cold-water fish would depend on what the fish were fed.

The general consensus on the Internet appears to be that wild-caught salmon is in all ways superior to its "industrially produced" counterpart from the large fish farms. In that, the opponents of farmed fish consumption usually highlight the (I quote) "exorbitant" amount of allegedly unhealthy omega-6 fatty acids in farmed fish.

Now it is certainly undebatable that the ratio of omega-6 to omega-3 fatty acids in wild-caught vs. farmed salmon differs significantly. The previously mentioned study by researchers from the Commonwealth Scientific Industrial Research Organization does yet also show that this effect is not a result of "farming", per se. Rather than that, the increase in omega-6 and decrease in omega-3 fatty acids in today's industrially produced cold-water fish is a result of the ongoing reduction of the fish(oil) content in the fish food.

Figure 1: Fatty acid profile of farmed and wild-caught baramundi in 1998, 2002 and 2010 (left) and the corresponding omega-3 to omega-6 ratios (right) – it's worth noticing that "back in the day" of high fish oil diets, the farmed barramundi had a more favorable omega-3 to omega-6 ratio than their wild-caught relatives (Nichols. 2014)

In 2001, for example, when farmed barramundi (Lates calcifer | another cold-water fish that is raised in large aqua-farms these days) were still fed a high percentage of dietary fish oil, the farmed fish actually had a more favorable omega-3 to omega-6 ratio than its wild-caught counterpart (see Figure 1).

Over the past 13 years, the fish farmers have yet replaced large amounts of the increasingly expensive fish oil in the feed by cheap poultry oils. The consequences are obvious: While this practice may reduce the levels of dioxins and dioxin‐like PCBs (Berntssen. 2005), the substitution of fish oil with vegetable oil in the feed lead to decreases in the total amount of PUFAs, most specifically omega-3s, though. Thus, the originally highly favorable omega-3/omega-6 ratios of 5:1 for farmed salmon and 3:1 for farmed barramundi has declined to a meager 1:1 (Nichols. 2014).

High omega-6 in today's farmed cold-water fish - a problem? For the average physical culturist who is following a diet that is comparatively low in potentially pro-inflammatory omega-6 fatty acids (they are only bad for you, when they are consumed in excess), tehe deterioration of the omega-3 to omega-6 fatty acid ratio in modern farmed vs. wild caught fish is relatively unproblematic. Unlike it is the case for the average Westerner, who is in dare need of high omega-3 and low omega-6 foods to balance his or her excessive omega-6 intake from vegetable oils and industrially processed foods, farmed salmon is thus still a good source of protein and fats for those of us who are following a whole foods diet with a balanced fatty acid profile.

So, if the relatively high omega-3 content is not a problem, because the effects of "high omega-6" farmed fish on your omega-3 to omega-6 ratio is still neutral (that's the case if the ratio is approx. 1) there is no reason to avoid farmed fish, right?

From "high omega-6" to high levels of organic and inorganic pollutants

Unfortunately the high omega-6 content is not the only problem farmed fish is supposed to have.  Next to the previously discussed issue, the occurrence of various pollutants in farmed fish is another of the topics that will be mentioned in almost every online- or gym-debate on the consumption of farmed fish. Rumors have it that farmed salmon was loaded with toxic chemicals. And guess what!? To a certain extend that is absolutely true.

Figure 2: Fish is by far not the only POP source in our diets. Each 0.5 serving of the above foods is associated with the given increase in µg of urinary phthalate and phenol biomarkers in the urine of 6-8 year old girls and may thus increase their breast cancer risk later in life (Mervish. 2001)

When we are taking a closer look at the latest scientific evidence on the real world effects of thes persistent organic pollutants (POPs), it turns out that a high fish consumption has no measurable impact on the concentration of this potentially cancerous endocrine disruptors (they mess with your hormones) in our blood and adipose tissue. In fact, the latest study by Hausken et al. clearly indicates that the POPs in the blood of their fish fed subjects and the corresponding control group have different food products as their main sources (Hausken. 2014).

It is thus no wonder that the researchers from the University of Bergen did not find any change in serum or adipose tissue POP levels, when they had their subjects, 42 outpatients with different metabolic disorders, increase their intake of farmed salmon or salmon oil and compared their subjects' serum and fat pollutant levels to a non-fish eating control group.

The results were unambiguous: The consumption of farmed fish did not affect the steady-state of organic pollutants in either the blood or fat tissue of the subjects.

High levels of persistent organic pollutant (POPs) - a problem? The ever-increasing amount of POPs in our diet and other consumer goods (deodorants, perfumes and cosmetics are another source of POP) is a problem and a potential threat to our health, but farmed fish is not the item on your plate or cupboard that will tip the scale.

Due to the ever-increasing pollution of the oceans, rivers and lakes, POPs and other pollutants are no "farmed fish" phenomenon, anyway. If you look at the results of a recent study from the Hong Kong Baptist University, for example, you will have to concede that "eating wild caught only" is not going to protect you from being exposed to chemicals like BPA (Wei. 2011).

Figure 3: Polycyclic aromatic hydrocarbon (PAH) content of farmed and wild-caught salmon samples (Easton. 2002).

Moreover, the amount of organic pollutants in farmed fish could be easily reduced if the producers were willing to invest more money into quality fish food. The results of a 2002 study by Easton et al. clearly indicate for example that the increased polycyclic aromatic hydrocarbon (PAH) content of farmed vs. wild caught salmon could be easily reduced if these organic pollutants were not already present in hilariously high quantities in the feed the fish are fed. Buying uncontaminated fish food would thus give the farmers a degree of control fishers whose wild caught chinook salmon can contain up to 4.8x  more PAH than farmed salmon (see Figure 3) will never have.

Fish oil can be POP free, but not everything that glitters is gold

Fish oil is a highly processed substance. If the processing is done right, it is possible to remove large parts of the previously discussed POPs, as well as inorganic pollutants like mercury from the fishy sludge. The fact that it can be pollutant-free, however, does not necessarily mean that your fish oil caps will actually be free of any harmful substances.


The fact that fish oil producers may not do their job properly is yet not the only reason I am a strong proponent of consuming whole vs. "capped fish" and a whole foods vs. processed "supplement diet.  Why? Well, fish is by far not the only so-called "superfoods" for which we have seen time and again that the isolation of certain ingredients, of which we think that they are what makes these foods so "super", is not going to yield the results we are looking for.

In fact, recent studies which highlight the benefits of fish proteins for man and women who strive to build and maintain a muscular physique (learn more in a previous SuppVersity article) clearly suggest that the often-cited high selenium content of fish is not the only "good thing" you'd miss if you ditch your salmon, tuna and other fatty fish for cheap and convenient fish oil caps.

Warning! "Whole fish" does not include fried fish as you will find it on a "fish mac" or fish & chips and/or fish sandwiches. An increased consumption of these "fish" meals has been shown not to influence the cardiovascular mortality risk of 3910 adults aged 65+ years in a 2003 study by Mozaffarian et al. Moreover, the previously discussed amount of environmental pollutants in the fish is another determinant of its beneficial health effects.

In an editorial comment in the Journal of Internal Medicine Jacobs, Ruzzin & Lee highlight that "[t]he evidence that environmental pollutants can affect the health benefits of fish is supported by previous experimental studies" (Jacobs. 2014). In rodent studies, only decontaminated farmed salmon oil ameliorated the negative effects of high fat feeding. A POP-laden salmon oil from Atlantic salmon, on the other hand, accelerated the development of insulin resistance-related disorders in the lab animals (Ibrahim. 2011). The question, whether we should eat fish and take fish oil supplements is thus intricately related to the question whether we can obtain POP-free fish and fish oil products.

Table 1: The amount of organochlorides in various types of fish oil supplements bought on the Canadian market can be significant - similar results have been found on other markets | ^aΣ of 1,2,3,4 tetrachlorobenzene, 1,2,3,5 tetrachlorobenzene, and pentachlorobenzene; ^bΣ of α-HCH, β-HCH, and γ-HCH; ^cΣ of oxychlordane, trans-chlordane, trans-nonachlor, and cis-nonachlor; ^dΣ of p,p′-DDT and p,p′-DDE.(Rawn. 2009).

And even if you're not interested in being muscular, a recent study by Brazionis et al. clearly suggests that getting your 1g of long-chain omega-3 fatty acids from fish vs. fish oil supplements "may have additional cardiovascular benefits beyond the omega-3 effect". Effects which lead to a significant reduction in blood pressure the scientists observed only in those subjects who consumed fresh salmon (two 150 g servings per week of John West fresh Atlantic salmon), but not in their peers in the fish oil arm of the study (Brazionis. 2012).

Is fish oil the safer alternative? If you buy your fish oil from a manufacturer who can prove that each and every batch is tested for its POP and heavy metal content, it may be safer, but in view of the synergistic effects of protein, fat, certain peptides and a plethora of micronutrients you will be missing if you scrap your two weekly servings of fatty fish and turn to fish oil caps instead, this does not mean that it will be healthier.

When we are talking about toxic substances in fish and fish oils, we obviously cannot dismiss the heavily debated issue of heavy metal contaminations.

Heavy metals are clearly no farmed-fish exclusive!

While the heavy metal issue is still a matter of open scientific debate, the epidemiological evidence in favor of the profound health effects of regular fish consumption appears to suggest that it is less of an issue for the general population than the hysteric news on the Internet may make you believe.

Figure 4: Mean (bottom axis) and max (top axis!) mercury content (mg/kg) in fish (FDA Monitoring Program. 1990-2010 from a 2012)

For fitness junkies and bodybuilders who are trying to satisfy their alleged protein "requirements" of 3-4g of protein per kg body weight by shoveling down one can of tuna after the other, however, the heavy metal content of the cheap fish cans may become a problem.

Or maybe I should say: I personally would not use canned tuna as my primary protein source, when aiming for a protein intake of 3-4g per kg of body weight.

And this goes regardless of the fact that I believe that the risks associated with consuming tuna containing 0.10-0.75ppm methyl mercury (Yess. 1993) may be overblown in some of the sensationalist articles on the Internet and other mainstream media.

Similarly, I am reluctant to rely on the purported protective effect of the high amounts of cysteine and selenium in seafood. A protection, by the way, of which scientists have recently shown that is cannot mitigate the loss of cardioprotective effects of high omega-3 intakes in individuals with high hair mercury levels (Virtanen. 2009 | learn more).

So mercury is less on an issue than people claim? Probably yes. I would subscribe to the FDA recommendation to limit your fish intake to 2-3x fish meals a week. More specifically, you should forget about the idea of tuna as a "healthy snack" you can eat as often as you want to and stay away from more than one fish meal if you are pregnant or trying to become pregnant. In this case buying either mercury controlled fish or fish oils may in fact be the better choice  – I mean: "Better save than sorry", right?

Speaking of fish oil, there is an increasing trend towards krill oil as the "hype" omega-3 supplement. A trend of which you, as SuppVersity readers know that it appears to be unwarranted, although krill oil has the advantage of providing a large amount of the omega-3 fatty acids in their phospholipid-bound form (learn more in a previous SuppVersity article).

Figure 5: Plasma, liver and white adipose tissue (WAT) levels of triglyceride (TL) and phospholipid varieties of DHA+EPA after 9 weeks on HFD diet with (w3TL or w3PL) or  w/out 30mg/kg chow DHA + EPA (Rossmeisl. 2012)

Compared to triglycerides, the phospholipid-bound version is easier to assimilate. Accordingly, it is not very surprising that Rossmeisl. et al. (2012) were able to show that phospholipid-bound long-chain omega-3 fatty acids increase the plasma and liver omega-3 content to a significantly greater degree than the same amount of triglyceride-bound omega-3 fatty acids. An effect that was – at least in rodent studies – associated with a significantly more pronounced reduction in fat cell size and insulin sensitivity (Rossmeisl. 2012).
A more recent study by Tillander et al. (2014) adds to the evidence that krill oil may have an edge over fish oil, as an anti-NAFLD agent, because it will epigenetically reduce the fatty acid synthesis in the liver (read more).
 
The very ability to reduce the synthesis of fatty acids in the liver makes krill oil particularly interesting for overweight and obese people.

The increased fatty acid oxidation in response to the ingestion of fish oil (vs. krill oil) the researchers observed in the same study, on the other hand, may be something that could be of interest for lean individuals who are trying to lose weight (learn more in previous SuppVersity article).

Fish or krill? It depends... The previously presented evidence does thus make one thing very clear: It is more than likely that it will depend on your goals and current health status which of these omega-3 sources you should prefer. Overall, there is yet still a paucity of independent research, which is why I would not be surprised if the previously made conclusions were refuted by future studies.

If not weight loss, but muscle gains and fat loss are your goal, though, neither fish nor krill oil will do - at least not in the absence of one of the previously mentioned synergists: Fish protein!

Fish protein, an overlooked anabolic?

What wanna-be bobybuilders need is protein. Fish protein, to be precise. In 2009, for example, Ramel et al. were among the first to observe that using fish, or more specifically cod protein as the major protein source in the diet of their overweight subjects would yield improved outcomes in terms of fat loss and lean mass retention (Ramel. 2009; see Figure 6).

Figure 6: Decreases in anthropometric measurements after the 8-week intervention with isocaloric energy reduced diets having in obese subjects consuming no, three or five servings of lean fish per week (Ramel. 2009).

It is thus quite obvious that there must be something special to fish proteins more common dietary protein sources do not provide.

This hypothesis is also supported by previous evidence from rodent studies. One of these studies that was conducted by Frédéric Tremblay et al. (2003) at the Laval University Hospital Research Center suggests that the benefits may be related to the potent anti-inflammatory effects of fish proteins, which will thus increase the muscular insulin sensitivity and favor fat over muscle loss and muscle over fat gain.

A more recent study by Vikøren et al. (2013) seems to confirm this hypothesis.

The overweight adults who participated in the corresponding experiment experienced significant improvements in glucose metabolism, increases in lean and decreases in fat mass, when the scientists added 3 g of fish protein per day to their diets for the first 4 weeks and 6 g/d for the last 4 weeks of the 8 week intervention.

Figure 7: Macronutrient composition of the diets at baseline, after 4 weeks and 8 weeks and changes in body composition compared to baseline (Vikøren. 2013 - learn more in a previous SuppVersity article)

What is particularly noteworthy about this study is the fact that these effects occurred in spite of the fact that "[p]hysical activity and energy and macronutrients intake did not change during the course of the study" (Vikøren. 2013).

More recent evidence from a rodent study by Kawabata et al. (2014) strengthens the "anti-inflammatory" hypothesis. In their experiments, the researchers compared the effects of casein and fish protein in a tightly controlled dietary intervention and found similar increases in muscle mass and improvements in glucose metabolism in their hairy subjects as Vikøren et al. did one year before in overweight adults (learn more in a recent SuppVersity article).

Why don't we use our consumer money to force producers to make a change? I hope my previous elaborations have made it clear that living off fish as your only protein and fat source in the diet is probably not the best idea. On the other hand, similar issues with antibiotics (ab)use, persistent organic pollutants (POP) and even mercury exist for other foods, as well – with the exception of antibiotics which are only used to produce animal products all these pollutants can also be found in veggies and fruits (so no "vegan advantage").

We would thus be good advised to use our most powerful weapon, i.e. consumer money, to steer the food industry away from doing everything to cut the production costs and buy fish from those farms that don't use cheap poultry instead of fish oils, intoxicate the water with antibiotics and buy the cheapest, yet POP-laden food from questionable sources in China to feed their fish.

Time to draw some conclusions: Based on the existing evidence there is no reason to shy away from either fish consumption, in general, or the consumption of farmed fish, in particular. The overwhelming majority of epidemiological evidence indicates that consuming two servings of fatty fish a week will have nothing but beneficial effects on your overall health and that in spite of the fact that the fish was not controlled for organic or inorganic pollutants in any of these studies.

Whether it makes sense to consume large quantities of fish on a daily basis is yet as questionable as the routine use of fish oil supplements. Most of us will be able to cover our fundamental omega-3 needs with the previously mentioned two servings of fish per week. Consuming more than that in supplemental form is – in my humble opinion – not necessary for healthy individuals, unless they need to balance their exuberant intake of omega-6 fatty acid from large quantities of vegetable oils and processed foods in their diets –both products of which I highly recommend that people limit their intake to a minimum.

Moreover, imbalanced diets that are dominated by a single food source have repeatedly been shown to increase one's risk of running into severe health problems in the long run. So why don't we combine fish with dairy products, grass fed beef, pork and vegetable protein sources to create a varied, tasty, health and physique promoting high protein diet we can follow for the rest of your lives, instead of looking for the one "superfood", of which I would hope that most of the people who read this interview will know by now that it doesn't exist, anyway.

References:

• Brazionis, Laima, et al. "The effects of fish or fish oil on the omega‐3 index." Nutrition & Dietetics 69.1 (2012): 5-12.
• Berntssen, Marc HG, ANNE‐KATRINE LUNDEBYE, and Bente E. Torstensen. "Reducing the levels of dioxins and dioxin‐like PCBs in farmed Atlantic salmon by substitution of fish oil with vegetable oil in the feed." Aquaculture Nutrition 11.3 (2005): 219-231.
• Easton, M. D. L., D. Luszniak, and E. Von der Geest. "Preliminary examination of contaminant loadings in farmed salmon, wild salmon and commercial salmon feed." Chemosphere 46.7 (2002): 1053-1074.
• Hausken, Trygve, et al. "High Consumption of Farmed Salmon Does Not Disrupt the Steady State of Persistent Organic Pollutants (POP) in Human Plasma and Adipose Tissue." Journal of Toxicology and Environmental Health, Part A 77.20 (2014): 1229-1250.
• Ibrahim, Mohammad Madani, et al. "Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice." PloS one 6.9 (2011): e25170.
• Mervish, Nancy, et al. "Dietary predictors of urinary environmental biomarkers in young girls, BCERP, 2004–7." Environmental Research 133 (2014): 12-19.
• Mozaffarian, Dariush, et al. "Cardiac benefits of fish consumption may depend on the type of fish meal consumed the cardiovascular health study." Circulation 107.10 (2003): 1372-1377.
• Nichols, Peter D., et al. "Readily available sources of long-chain omega-3 oils: is farmed Australian seafood a better source of the good oil than wild-caught seafood?." Nutrients 6.3 (2014): 1063-1079.
• Rawn, Dorothea FK, et al. "Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides." Journal of food science 74.1 (2009): T14-T19.
• Rossmeisl, Martin, et al. "Metabolic effects of n-3 PUFA as phospholipids are superior to triglycerides in mice fed a high-fat diet: possible role of endocannabinoids." PLoS One 7.6 (2012): e38834.
• Tillander, Veronika, et al. "Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice." Gene expression 24 (2014): 28.
• Tremblay, Frédéric, et al. "Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat-fed obese rats." Diabetes 52.1 (2003): 29-37.
• Vikøren, Linn A., et al. "A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults." British Journal of Nutrition 109.04 (2013): 648-657.
• Virtanen, Jyrki K., et al. "Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men." Circulation 120.23 (2009): 2315-2321.
• Wei, Xi, et al. "Assessment of risk to humans of bisphenol A in marine and freshwater fish from Pearl River Delta, China." Chemosphere 85.1 (2011): 122-128.
• Yess, N. J. "US Food and Drug Administration survey of methyl mercury in canned tuna." Journal of AOAC International 76.1 (1993): 36.

Underestimated Vitamin D Sources: Especially Eggs, But Also Chicken, Pork, Fish & Dairy Contain an Overlooked, Physiologically Relevant Amount of Ready-Made 25OHD

What do you need for a high 25OHD picnic on day at the beach? Eggs!

Regular SuppVersity readers know: The slowly abating vitamin D hype is driving me up the walls. Whenever you search a database for recent articles with the word "vitamin" in it, you are flooded with papers on vitamin D - many of them simplistic adulations without any new data or information. Others are totally irrelevant experiments on cell lines or non-significant epidemiological analyses, where no one can tell you whether the low vitamin D levels are mechanistically or corollarily involved in whatever the scientists are trying to tell you vitamin D was beneficial for.

Among all this mess, you can still find a handful of interesting papers. You just have to look close enough to spot gems such as a review by Ovesen, Brot and Jakobsen (2013).

Are Eggs the Best Dietary Vitamin D Source We Have?

"Eggs? The best vitamin D source?" I don't have the hubris to say that eggs are the absolute #1, but considering the fact that eggs are the #1 source of "actual", preformed 25OHD, aka 25-hydroxyvitamin D*, in our diets, you are probably going to agree that eggs may well be the most underrated source of vitamin D in our diet (25OHD is what doctors and scientists will measure in your blood stream; most essays measure total 25OHD, so I will not differntiate the different forms here).

Preformed vitamin D? Isn't that dangerous? No, quite the opposite: Pharmacologic doses of 25OHD do not change or may even decrease plasma levels of 1,25(OH)D, aka calcitriol, which can potential cause calcification (Trummel. 1669; Heaney. 1997). When you are D-ficient, though, your body will retain the 25OH. This is particularly interesting for people with intestinal malabsorption, for whom 'regular' vitamin D supplements, i.e. vitamin D3, aka cholecalciferol, or vitamin D2, aka ergocalciferol, don't work (Francis. 1983)

When it comes to vitamin D, eggs, fish, dairy, meat and offal are quite unique. All of them contain "vitamin D" in the still-to-be-converted D3 form you all know. What only few people know is that they also contain the celebrated vitamin D metabolite 25-hydroxyvitamin D (25OHD). This is not only the form your doctor will measure, when you ask for a "vitamin D test", it's also the "vitamin D" that has been linked to all sorts of health benefits in the aforementioned epidemiological studies.

If you want to increase or maintain your 25OHD levels, it is obviously an advantage if you don't have to rely on your body to transform the dietary D2 + D3 into 25OHD. It is even better though, if the efficacy of this "supplement" (as of now I have not seen 25OHD in caps, so you better stick to eggs) has a higher bioavailability than its non-polar precursor, vitamin D3, which is absorbed mainly into the lymph (Thompson. 1966; Blomstrand. 1967).

"[T]he more polar metabolite 25OHD at physiological concentrations is also absorbed directly, and more rapidly and efficiently, from the proximal jejunum into the portal vein independent of fat absorption. These findings are consistent with results from clinical studies, which have found better absorption of 25OHD versus vitamin D in patients with fat malabsorption. Also, in healthy subjects and in patients with bone disease  25OHD is absorbed better and faster than vitamin D." (Ovesen. 2013)

I would hope that you are by now at least considering to eat an egg instead of popping dozens of vitamin pills. For those who still need actual data before they subscribe to the egg-ological approac to vitamin D 'supplementation', I have compiled a couple of figures in Table 1:

Table 1. 25OHD content (µg/100g) of chicken & egg, pork, beef, fish, dairy (various sources; cf. Oveson. 2013)

With respect to fish it's worth mentioning that the exact concentrations vary from species to species. Moreover  25OHD content of fish is distributed relatively evenly in muscle, fat and organ mass of the fish - much in contrast to vitamin D3, by the way, which is contained mostly in the organs, specifically the liver. For the average human being this means that he or she will actually get his / her share of 25OHD with every serving of fish. For vitamin D3 that's clearly not the case, because few of us actually eat cod liver on a regular base.

The sentence "You Eat What You Feed" is not new to SuppVersity regulars - it's also the title of an older article discussing how you can use food additives to increase the Omega-3 content of your steaks, milk and other animal products | read more

Another thing we should not forget is the influence of the diet. As you as a SuppVersity reader know, it's very difficult to predict the exact amount of almost every nutrient you will get from the products you buy at the super market, in this day and age of food supplements and synthetic chow (see "You Eat What You Feed: How Much Omega-3s Can You Possibly Pack into a Single Steak? The Impressive Effects of a "Grass(+)" Diet on Raw Meat & Meat Products" | read more).

If you ate the bacon of the pigs in the Thompson study from the late 1960s, for example, you would get a whoppy dose of 0.7–2.0µg 25OHD per 100g and thus max. 10x more than from regular bacon. Why? Easy: The sows were on a(n extremly) high vitamin D diets (total D-intake was 2–3mg/day for 2-3 weeks; Thompson. 1966).

What's the "minimal" vitamin D level: If we take the most recent study by Tepper as our guide, you need much less vitamin D to keep your heart disease risk, or rather the markers that have been associated with the latter in check.

In their study, the scientists measured the vitamin D levels of 400 healthy men (age 25-65 years) and identified their relationship to fasting plasma insulin (FPI), fasting plasma glucose (FPG), triglycerides (TG), high sensitive C-Reactive Protein (hs-CRP), blood pressure and triglycerides and found that (a) vitamin D status is related to cardiometabolic indicators in healthy men and that (b) their data would suggest that 11−14 ng/ml should be defined as the minimal vitamin D threshold. So, if you are below that mark you are in for trouble and supplementation actually necessary.

Egg yolks instead of pills? The question, whether you can trash your vitamin D3 (or D2) supplements, as long as you make sure you get your daily dose of egg yolks (the 25OHD is in the yolk, not the egg white!), is difficult to answer. The 'potency' of oral 25OHD is estimated to be 1.5-5x higher than the one of 'regular vitamin D3' the form of 'D' you will find it in the majority of OTC supplements. Since we don't even know how much D3 a given individual actually needs the best thing you can do is to get tested, even if the estimated equivalent values and bioactivity were accurate.

The optimal dietary / supplemental intake is not the only thing that's still highly debated, though. The "optimal" serum levels are similarly dubious. While there appears to be a consensus that you would be ill advised not to take action, when your 25OHD levels come back in the deficiency zone from 30ng/ml-0ng/ml, the answer to the question whether it makes sense to opt for the 'magic' 80ng/ml depends on the expert you ask.

In view of the emerging importance of free vs. total vitamin D, the 25OHD number (=total) on your blood test may soon be deemed completely irrelevant, anyways. There are after all numerous recent studies that support the hypothesis that free 25OHD and not total 25OHD is, where the magic happens. In fact, I have only recently covered two of them in the SuppVersity Facebook news. News-item (1) deals with vitamin D binding and insulin resistance (read more) and news-item (2) addresses the correlation between the free vitamin D and lipid levels in the blood.

References: 

• Blomstrand R, Forsgren L: Intestinal adsorption and esterification of vitamin D31,2-3H in man. Acta Chem Scand 1967;21:1662–1663. 
• Francis RM, Peacock  M, Storer JH, Davies AEJ, Brown WB, Nordin BEC: Calcium malabsorption in the elderly: The effect of treatment with  oral  25-hydroxyvitamin  D3.  Eur  J  Clin Invest 1983;13:391–396. 
• Heaney RP, Barger-Lux MJ, Dowell MS, Chen TC, Holick MF: Calcium absorptive effects of vitamin D and its major metabolites. J Clin Endocrinol Metab 1997;82:4111–4116. 
• Ovesen L, Brot C, Jakobsen J. Food contents and biological activity of 25-hydroxyvitamin D: a vitamin D metabolite to be reckoned with? Ann Nutr Metab. 2003;47(3-4):107-13. Review. 
• Thompson GR, Lewis B, Booth CC: Absorption of vitamin D3-3H in control subjects and patients with intestinal malabsorption. J Clin Invest 1966;45:94–102. 
• Trummel CL, Raisz LG, Blunt JW, DeLuca HF: 25-Hydroxycholecalciferol: Stimulation of bone resorption in tissue culture. Science 1969; 163:1450–1451. 

Meta-Analysis Says: Fish Oil Does Not Help You Lean Out! Plus: Why It's Still Worth Having Fatty Fish 1-2x/Week

SuppVersity readers know: Diet (and exercise) will make you lose weight. Supplements can only accelerate the process. However, it it really possible that fish oil does not even do that?

I guess those of you who are still taking it, will already have noticed that there is nothing to the whole hoopla about the "fat burning effects of DHA & EPA". A recent meta-analysis from the University of Sheffield in the United Kingdom does now confirm just that: The hypothesis that daily fish oil supplementation reduces body weight and BMI is not supported by scientific evidence -at least not in the overweight and obese study participants of the 9 studies that met the rigorous criteria of this meta-analysis.

The scientists had conducted a search of Web of Science, PubMed, Medline and Google Scholar for studies having the keywords ‘fish’, ‘fish oil’, ‘oily fish’, ‘omega three’, ‘omega-3’, ‘n-3’, ‘body weight’, ‘body composition’, ‘BMI’, ‘weight reduction’ or ‘weight loss’ in them.

SuppVersity Sneak Peak: While it may not be directly related to fish oil, it will certainly border on the issue of weight and more importantly fat loss, as well: Today's Special of the SuppVersity Science Round-Up (tune in live at 12PM EST) discussing all you need to know about endogenous and exogenous (=supplemental) DHEA (not to be confused with DHA ;-) No idea what that could be? Well, what about adrenal fatigue, insulin resistance, low / high testosterone, aromatization, dosages, clinical & anecdotal evidence, etc. EDIT: Due to technical difficulties the show is going to be postponed. I will let you know on Facebook, when I know the day it will be aired (probably sometime next week, not necessarily Thursday).

From the query results, they filtered all papers that were not based on randomized controlled trials, had not compared the effect of fish oil supplementation with another (non-n-3) oil control [this is actually pretty interesting, because many trials simply throw the omega-3s on top of the regular diet and who can say that a spoon of olive oil would not have had similar, if not even more pronounced effects], had not used overweight or obese subjects and had not taken pre- and post-intervention measurements of body weight and BMI. Actually the fact that all of what they were left with were only 9 study is at least in my humble opinion an important result of this meta-analysis that tells you something about the "quality" of the omega-3 supplementation research out there.

Figure 1: Whether the participants received fish (FO) or placebo oil (PO) supplements did not make a difference; in fact, the results look (but aren't) slightly better in the placebo trial, usually (Harden. 2013)

The data I compiled in figure 1 gives you an overview of the results of the meta-analysis. It's not difficult to see that the remaining 9 studies clearly indicate that it is unrealistic to expect any direct effect on diet and/or diet + exercise induced weight loss.

---

Bottom line: While the weight loss effects of fish oils are in fact totally overblown, it should not be overlooked that their beneficial effects on the inflammatory processes that are particularly pronounced during phases of weight gain can ameliorate (but not blunt) many of the ill health effects that arise as a consequence of the steady increase of the adipose organ. I have previously discussed the possibility of becoming what scientists love to celebrate as "healthy obese" person by soothing the sickening inflammation that would otherwise increase with every pound of extra-weight. Now you would thus still end up being fat, but you would get rid of the fat much easier and most importantly without permanent damage to your health.

Figure 2: Effects of 2.8 g/day omega-3 supplement on reductions in weight, waist and hip width in severely obese women on very low carb, very  low fat low protein 550kcal diets (Kunesova. 2005)

Based on studies by Kunesova and Hlavaty from the years 2005 and 2008, respectively, n-3 supplementation can also offset the negative effects of crazy low carb + low energy diets, as they are used to treat severely obese men and women, they can keep the fatty acid composition of the serum lipids normal and help enhance body weight and more importantly body fat on low carb diets (as signified by the superior reduction in waist circumference; cf. figure 2) loss.

So, irrespective of whether you are trying to lose or gain weight, the 1-2x servings of fatty fish I would recommend as a preferred source of omega-3 fatty acids should remain a staple of your diet. If not for weight loss purposes, then for their beneficial effects on your overall health.

Additional reads:

• "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
• "The Pro-Diabetic Effects of Shark Liver Oil - Plus: Can it Be Coincidence that the Omega-6-Laden Nigella Sativa Oil has Just the Opposite Effects on Blood Glucose & Triglycerides" | learn more
• "Obese Vegan Salmon!? Vegetable Oils and Proteins Reduce DHA and EPA Content by -28% and Increase Overall Adiposity and Triglyceride Levels in Atlantic Salmon." | get the details
• "Fish Oil W/ High Peroxide Levels Is Useless and Can Negate the Beneficial Health Effects of an Omega-3 Rich Diet. Plus: 3 Tips to Help You Make the Right Fish Oil Choices" | learn more
• "Making the Right Fish Choices: Fatty Acid Contents of 33 Different Fish Species. Plus: What Are the Implications?" | make the right choice

References:

• Harden CJ, et al. Preliminary meta-analysis of the effect of fish oil on body weight and body mass index in overweight and obese subjects does not support a link. Proceedings of the Nutrition Society(2013), 72 (OCE4), E283
• Hlavatý P, Kunesová M, Gojová M, Tvrzická E, Vecka M, Roubal P, Hill M, Hlavatá K, Kalousková P, Hainer V, Zák A, Drbohlav J. Change in fatty acid composition of serum lipids in obese females after short-term weight-reducing regimen with the addition of n-3 long chain polyunsaturated fatty acids in comparison to controls. Physiol Res. 2008;57 Suppl 1:S57-65.
• Kunesová M, Braunerová R, Hlavatý P, Tvrzická E, Stanková B, Skrha J, Hilgertová J, Hill M, Kopecký J, Wagenknecht M, Hainer V, Matoulek M, Parízková J, Zák A, Svacina S. The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women. Physiol Res. 2006;55(1):63-72. Epub 2005 Apr 26.

Mercury, From Fish to Toenail; Less Testosterone Needed W/ TRT + Tongkat Ali; R,R-Monatin the Next Stevia From South Africa! Plus: Magnesium Protects Mitochondria from LPS & Caffeine Arteries from HIIT Induced Platelet Activity!

Image 1: Looks like the Terminator was concerned about "bone" health, maybe he should consider Tonkgat ali as an addition to his TRT... or whatever regimen;-)

If you want to, you can call today's news a special installment of "On Short Notice", I have already had a couple of interesting news and before I am piling up another truckload, I thought I could make at least some of you happy and put a handful of them out before the Super Human Radio & SuppVersity Science Round-Up on Thursday (you better make time to listen live, Thursday, 12PM/EST and download the first installment if you haven't done so, already ;-) and the "official" Saturdaily installment of "On Short Notice", here at the SuppVersity.

So let's see what we have here: Contrary to the order in the headline we will check out your toenails later, after all, I don't know what they look like and don't want to kill your appetite so that you cannot fully appreciate the findings of Fry et al. who discuss the potential application of an extract from the bark of Sclerochiton ilicifolius A.Meeuse as an all natural sweetener that's probably at least as, if not sweeter than stevia and - you guessed it - 100% calorie free! The same, i.e. being calorie free is obviously true for magnesium aspartate... whatever, in view of its potent protective effects against lipopolysaccharide induced mitochondrial damage and decay, you should not care about that, anyways.  And despite the fact that I would hope that the same goes for the minor pro-thrombotic effects of interval training, there may be one or another of the SuppVersity readers who's having issues with platelet activity already and will therefore be relieved to hear that a cup of coffee before your workout will not increase, but rather decrease the risk of thrombosis in response to the post-exercise increase in platelet activity.

You don't want to miss this week's installment of the joint Super Human Radio + SuppVersity
Science News Roundup - the show airs each Thursday, 12PM/EST (tune in live!)

The latter, i.e. the risk of thrombosis would by the way be even higher, if you were one of Xun et al.'s study participants who consumes one or more servings of fish per day. This would place you at greater risk of having high toenail mercury levels and with those being representative of whole body and tissue mercury levels you would already have higher baseline platelet activity than Mr. or Mrs. Healthy Average Joe, which would probably be a reason for your doctor to tell you that he cannot, by any means, put you on TRT (testosterone replacement therapy) - and that even if you were about as hypogonadal as the castrated rats in the Saadiah Abdul Razak study from the latest issue of Evidence Based Complementary Medicine. A study by the way you could print, show it to your doctor and say: "Look, I don't want to lose my muscle and break my bone, so let's do this you give me a script for low dose TRT and I get myself some quality Eurycoma longifolia extract and we will see how my values look like in 6 weeks from now." 

You see, as usual, even doctors can learn something, here at the SuppVersity so let's not put them on the rack for another paragraph or two and start right with our first item for today:

• 

  Image 2: Could the bark of these twigs from a spiny-leafed, hardwood shrub from South Africa hold a likewise natural stevia alternative?

  Is R,R-Monatin the new stevia? I know you all love your stevia, but there are people who simply hate the taste and still don't want to resort to any of the dubious sugar alcohols let alone the 100% artificial sweeteners, who may be interested that John C. Fry and a couple of other researchers published ad paper on a novel all natural sweetener from the bark of a South African spiny-leafed, hardwood shrub that goes by the name of  Sclerochiton ilicifolius A.Meeuse (Fry. 2012).
  According to the Fry et al., the compound has a potency above 3000 at 5% sucrose equivalent, which would make it (theoretically) even sweeter than stevia. Since the latter hit the market, we do yet all know how unrealiable these theoretical values are so that we will probably have to wait until the first monatin-based sweeteners become available - and you as a SuppVersity would be the first to know what's in there ;-)
  If we assume that there are no hitherto undisclosed health issues with monatin and it does in fact taste sweet and not disgusting, metallic or whatever, it is also likely that we are going to see new "proprietary" blends of stevia + monatin, similar to their artificial counterparts you still see in Coke Zero & Co - the quasi "natural" way to get as close as possible to the "true sugar taste", people are still craving, these days... if they don't hurry, I do yet doubt that there will be a market for products like that very long, as we are more or less trained to crave the "real sugar" taste, but this would be the topic for another blogpost ;-)

• 

  Figure 1: Effect of different doses of pre-supplementation with magnesium aspartate on markers of LPS induced mitochondrial decay, antioxidant activity and oxidative damage (data calculated based on Ahmed. 2012)

  250mg/day magnesium counter the metabolic derangements from lipopolysaccharide (LPS) intoxication When Lamiaa A. Ahmed added 20mg/kg or 40mg/kg (~125mg or 250mg in human equivalents) of magnesium aspartate to the chow mice that were pretreated with LPS injections, the researcher from the Faculty of Pharmacy at the University of Cairo found that this regimen restored body temperature (low dose) and heart rate (high dose) of the profoundly inflamed to normal, restored the lowered glutathione levels (both doses) and reduced (low dose) and normalized (high dose) the elevated creatine kinase (marker of cell damage) and thiobarbituric acid reactive substances (TBARS; marker of oxidative damage) levels that had been elevated by the lipopolysaccharide treatment (Ahmed. 2012).
  The ATP:ADP ratio, the activity of the sodium potassium pumps and the creatine phosphate levels (CrPh protects the cell wall from damage as you remember from a previous installment, right?) were not completely restored to, but the pathological changes were minimized dose-dependently. In conjunction with the normalization of the lactate to pyruvate ratio, a sign of either exertional exercise or - if it occurs at rest, as it does here - mitochondrial failure, these observations indicate that Mg therapy could be a reliable protective agent in LPS-induced cardio- and general myotoxicity. In that it should be noted that higher, but not exorbitantly high (250mg is roughly 2/3 of what you should aim to get from our diet everyday, anyway) doses were more effective in reducing cell membrane damage as well as in improving the intracellular acidosis, energy production, oxidative stress and Na+,K+-ATPase activity and corresponded with a better perseverance of the mitochondrial ultrastructure.
  And while Ahmed sees the main application of Mg aspartate therapy in "critically ill" patients, I would say that the large group of patients (and non-patients) with other pathologies such as a leaky gut would benefit as well, since the defective gut barrier opens the door for the "excrements" of your gut bacteria, to induce all sorts of pathologies including mitochondrial damage and decay, but also depression, obesity, diabetes, etc. (Maes. 2008; Musso. 2010)... and before I forget to mention it is not unlikely that cheap magnesium citrate (if tolerated) would do the job just as well - maybe in a slightly higher dosage of say 300mg per day (best taken in divided doses with food).

• 

  Image 3: Coffee is full of wonders ;-)

  Antithrombotic effects of caffeine blunt platelet activity in response to interval training The use of 3mg/kg (equiv. to ~1 large cup of strong coffee or 2 smaller cups of regular coffee) of caffeine as an ergogenic aid during aerobic interval training cannot just improve your performance, it will also prevent the pro-thrombotic platelet function activation that occurs during exercise. That's the somewhat surprising finding of the one of the latest studies from the Health Innovations Research Institute at the School of Medical Sciences on the campus of the RMIT University in Melbourne, Australia (Whittaker. 2012).
  Whether this effect is of any importance to you certainly depends on your personal health. Personally, I would say that it is negligible for the vast majority of people who engage in strenuous athletic activities, if you belong to a risk group where platelet function is either high (risk of developing thromboses) or low (risk of bleeding) you may want to keep these results in mind.
  And if you don't care about platelet function, you may be considering to have another cup of coffee, when I tell you that ~3 cups per day appear to offer some protection against skin cancer, parkinson's and non-alcoholic-fatty-liver disease (click on the links to read the full stories on the SuppVersity Facebook Wall).

• 

  Image 4: Remember last week's post on the mercury in fish and how it's not simply excreted with the selenium, let alone the cysteine it's bound to? It looks like the toenails of young Americans would confirm those lab results.

  Something fishy about toenail mercury levels I guess all of you will remember my "shocking" post about the mercury toxicity from fish (cf. "Mercury in Fish NOT Harmless, Regardless of Cysteine, Selenium, EPA or DHA!"), this one could actually go as sort of a follow up post, as it deals with the real-world consequences of mercury exposure and the subsequent deposition of the heavy metal in the toe nails of the 4,344 American male and female participants (age 20–32y) in the CARDIA Trace Element Study researchers from the Gillings School of Global Public Health and School of Medicine at the University of North Carolina have recently examined (Xun. 2012).
  I know, it may sound gross, but toenails have, among the various biological specimens you could theoretically analyze, the advantage of providing a relatively reliable long-term measure of Hg exposure (from a few months to a year), are easily collected, transported,stored, and cleaned and are relatively sheltered from environmental contaminants and less likely to be contaminated by shampoo, hair treatments, and medication (Morris. 1983, He 2011).

  

  Image 5: Who would have thought that your toenails provide a way better measure of the toxic load you have accumulated than your hair, for example? Just looking at them is yet not enough for a thorough analysis

  Since the Hg levels in toenails also have relatively high correlation with both mercury intake (r = 0.54; Ohno. 2007) and the mercury deposition in critical organs (spec. in the brain - r = 0.65 ; Bjorkman. 2007), it should be obvious that the association between toe nail mercury levels and fish intake in all, but those participants who lived in Oakland and had the lowest (0.45 servings per day) fish intake per day could have a significant impact on the health of the subjects that consume more than one serving of fish per day and have a 76% higher beta coefficient of the natural logarithm of toenail Hg level than those who consume fish / seafood less than once per day (this mean that the mercury in the toenails of daily fish eaters increases 75% more rapidly towards that level than in those who eat 0.35 to 1.03 servings). Interestingly this was particularly true for the Caucasian men in the study, where the beta coefficient was another 45% higher (beta = 0.64 vs. beta = 0.44).
  Despite the fact that these results seem to confirm that eating one dose of untested canned tuna (which would probably go as way more than one serving in the eyes of the scientists) is not necessarily the best idea. It does however not mean that you cannot have you once or even twice a weak salmon steak or sushi - just keep your diet more versatile and don't make fish (or any other single foodstuff your only "allowed" source of protein or fat.

• 

  Figure 2: Weight of castrated rats on TRT, TRT (50% dose) + Eurycoma longifolia  (EL) or Eurycoma longifolia, alone, at the end of the 6-week supplementation phase, ratio of bone building osteocalcin to CRX a marker of bone resorption and actual bone strength, as measure by maximal tolerable load and Young's Modulus; all data expressed relative to sham operated (=intact) rats (data calculated based on Saadiah Abdul Razak. 2012)

  Low dose testosterone + long jack better than TRT alone? The results Saadiah Abdul Razak et al. present in the latest issue of Evidence Based Complementary Medicine don't actually look like they were interesting for muscle heads, I mean "androgen dependent osteoporosis", where are the word hypertrophy, skeletal muscle, or at least ripped & jacked? And I have to admit that of these only "skeletal muscle" makes its appearance somewhere in the introductory remarks of the discussion and only in the context of the "auxiliary functions" of testosterone as a growth hormone and IGF-1 booster and muscle builder. I do still believe that the data in the figure 2 on the right is going to get your attention - after all, the combination treatment of testosterone + Eurycoma longifolia did not "just" restore the balance of the "bone builder" osteocalcin to the "bone eater" ORX (actually it's just a marker of bone resorption) to normal (=sham levels), it did also effectively build the strongest bones, with the highest maximal load in Newton and the greatest elastic stability, as measured by the Young's Modulus.
  What's interesting, as well, is that all treatments were equally effective in restoring normal body weight - who knows maybe 15mg/kg/day (HED: 2.4mg/kg; ~170-250mg/day) of Eurycoma longifolia (EL) extract would even make a valuable stand alone (no pun intended ;-) testosterone booster for mild cases of real hypogonadism (not the one where your diet is shitty, your training sucks and it's your "low T" that you believe is to to blame that you make no gains), or an adjunct to HRT that would allow you to use only half the regular dose (this was done in the study at hand) and see similar results!? That it's good for sperm quality and testosterone, when it's administered in ~13x higher dosages in rodents (Chan. 2009) and for sperm health in men (at about the dosage used here; cf. Tambi. 2010) has already been established.
  And still, the "major gap" of which Bhat et al. postulated that it existed "in [sic!] providing scientific base for commercial utilization and clearance of the Tongkat Ali products with regard to consumer's safety" is still in existence. Moreover, the same could be said about our knowledge with respect to the individual effects of the potentially biologically active component(s) in the plant and respective extracts. Before those issues are not solved, the "extract" you may buy could be anything from uberpotent to simply toxic... although I suspect that it is still most likely that it will simply be ineffective.

What? That went too fast? Don't worry, it's just two days to the Thursdaily Science News Roundup on SHR, four days to the next official installment of "On Short Notice" and just one click away from a handful of additional up-to-the-minute news on the SuppVersity Facebook Wall such as

• the correlation of low growth hormone levels with NAFLD (= non-alcoholic fatty liver disease), 
• a study on how digestion potentates the antimicrobial activity of coconut oil,
• a potential successor to metformin that triples muscular glucose uptake in the absence of insulin 

and all the other interesting tidbits I have already and am still going to post there even before the next SuppVersity news is going to be published right here, tomorrow! Ah,... and by the way it's not prohibited to share articles you like on Facebook and other social media outlets ;-)

References:

• Ahmed, L.A., Protective effects of magnesium supplementation on metabolic energy derangements in
  lipopolysaccharide-induced cardiotoxicity in mice. Eur J Pharmacol. 2012.
• Bhat R, Karim AA. Tongkat Ali (Eurycoma longifolia Jack): a review on its ethnobotany and pharmacological importance. Fitoterapia. 2010 Oct;81(7):669-79. Epub 2010 Apr 29. 
• Bjorkman L, Lundekvam BF, Laegreid T, Bertelsen BI, Morild I, Lilleng P, Lind B, Palm B, Vahter M. Mercury in human brain, blood, muscle and toenails in relation to exposure: an
  autopsy study. Environ Health. 2007; 6:30 
• Chan KL, Low BS, Teh CH, Das PK. The effect of Eurycoma longifolia on sperm quality of male rats. Nat Prod Commun. 2009 Oct;4(10):1331-6. 
• Fry JC, Yurttas N, Biermann KL, Lindley MG, Goulson MJ. The Sweetness Concentration-Response of R,R-Monatin, a Naturally Occurring High-Potency Sweetener. J Food Sci. 2012 Aug 27.  
• He K. Trace elements in nails as biomarkers in clinical research. Eur J Clin Invest. 2011;  41(1):98–102.
• Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.
• Morris JS, Stampfer MJ, Willett WC Dietary selenium in humans: toenails as an indicator. Biol Trace Elem Res. 1983; 5:529–537.
• Ohno T, Sakamoto M, Kurosawa T, Dakeishi M, Iwata T, Murata K. Total mercury levels in hair, toenail, and urine among women free from occupational exposure and their relations to renal tubular function. Environ Res. 2007;103(2):191–1.
• Saadiah Abdul Razak H, Shuid AN, Naina Mohamed I. Combined Effects of Eurycoma
  longifolia and Testosterone on Androgen-Deficient Osteoporosis in a Male Rat Model. Evid Based Complement Alternat Med. 2012;2012:872406. Epub 2012 Aug 9.
• Whittaker JP, Linden MD, Coffey VG. Effect of Aerobic Interval Training and Caffeine on Blood Platelet Function. Med Sci Sports Exerc. 2012 Aug 29.
• Xun P, Liu K, Morris JS, Jordan JM, He K. Distributions and determinants of mercury concentrations in toenails among American young adults: the CARDIA Trace Element Study. Environ Sci Pollut Res Int. 2012 Aug 25.

Obese Vegan Salmon!? Vegetable Oils and Proteins Reduce DHA and EPA Content by -28% and Increase Overall Adiposity and Triglyceride Levels in Atlantic Salmon.

Image 1: Could this be made of obes vegan
salmon? (img from littlesteps.eu)

If you listened to yesterday's episode of Carl Lenore's Super Human Radio, you may remember that I repeatedly pointed out that "not all milk is created equal" and that milk quality is determined by food quality (if you want to read more about milk in general and colostrum in particular, I suggest you read last week's Ask Dr. Andro, as well). Today I am going to tell you about another of the industry's economic (in the monetary sense) ways of reducing the quality of animal foods in our foodchain - and we are talking about a food with a much better reputation than milk or beef: Salmon, the "heart-healthy cold-water fish" that is literally in on (or rather between) everyone's lips, lately.

Note: Salmon is explicitly mentioned in the "sample one-day menu" scientists at Colorado State developed according to the USDA dietary guidelines (Dietary Guidelines for Americans), so don't tell me you are not supposed to eat Norwegian fish, anyway, because you, my American friends, are supposed to have Grilled salmon, steamed broccoli, barley pilaf, low-fat milk and cake with fresh berries for dinner ;-)

Bente E. Torstensen and his (her?) collegues from the National Institute of Nutrition and Seafood Research and the Skretting Aquaculture Research Centre in Norway conducted an interesting experiment (Torstensen. 2011). For about a year, the researchers fed 6,000 smolt of Atlantic salmon (mean weight 355g) which had previously been randomly assigned to one out of three experimental + one control groups with diets containing...

• maximal amounts of fish meal and fish oil (Control)
• the "safe maximum replacement" of both fish meal and fish oil with plant meal (80% plant protein) and vegetable oil (70% vegetable oil) (80PP70VO)
• half the maximum replacement with plant meal (40%) and maximal replacement with vegetable oil (70%) (40PP70VO)
• maximum replacement with plant protein (80%) and half of the maximal replacement with vegetable oil (35%) (80PP35VO)

While the control diet obviously resembles what salmon, which primarily feeds on other fish, would naturally eat, the diet composition of group 2 remotely reminds me of what the food-industry has been feeding the less health-conscious masses in the US and Europe over the last decades. What... as a animal-loving vegan you are more interested in the fate of the poor salmon than in that of your sick and obese fellow human beings? Ok, here is what happened:

Maximum dietary VO [vegetable oil] and PP [plant protein replacements] increased visceral lipid stores, liver TAG, and plasma VLDL and TAG concentrations. Increased plasma TAG correlated with an increased expression of apoB100, indicating increased VLDL assembly in the liver of fish fed the high-plant protein- and VO-based diet.

Veganism, it turns out, ain't the preferable diet for salmon. Depending on which end of the dietary spectrum you belong to - the carnivorous hunter or the vegan gatherer -  you will probably now be asking yourselves one of the following questions:

1. Hunter: "What does that have to do with me? I always knew plant proteins and oils are bad for you!"
2. Gatherer: "What does that have to do with me? I don't eat salmon and the results from a 'fish-model' certainly won't apply to human beings!"

In isolation both the carnivorous hunter as well as the vegan gatherer appear right, when they ignore a prick like me citing the results of an insignificant fish study, the amalgam of both of these trains of thought does yet bring up a more unsettling question: What happens to the average health-conscious customer on a budget who thinks he is doing him/herself good by frying his economically raised, i.e. vegetable oil and protein fed, salmon in "healthy" vegetable oils and finishes dinner with a tofu dish? To be honest, I don't think we really need a study to answer that question. You just have to look at your peers to see the health consequences of eating sick animals and other vegetables that were either never intended for human consumption or have been (over-)processed beyond all recognition.

Figure 1: Relative changes in the fatty acid profile compared to "real", i.e. fish-fed, salmon after 1 year on vegetable oil and protein (data calculated based on Torstensen. 2011)

A pros pos "beyond recognition" if you have a closer look at the combined effects of vegetable oils and proteins on the fatty acid (figure 1) of the fish you will notice that industrially produced salmon fed with the "safe maximum replacement" dose of vegetable oils and proteins has little resemblance with the healthy food most consumers believe they were eating, when they buy "salmon" at the grocery store. Most obviously, the beneficial n3:n6 ratio of 7.6 in "real" salmon changed for the worse and ended up at roughly 3.0 after one year on a 80% plant protein 70% vegetable oil diet. Moreover, the individual composition of the fatty acids changed, as well. These changes include -28% reductions in EPA and DHA levels. After all, customers are left with something that looks like salmon, because it has been artificially colored, and tastes like "salmon", simply because 99% of the customers do not even know how "real" salmon would taste, because since the 1980s the ratio of wild-caught (real) salmon to farmed (fake ;-) Atlantic salmon has declined from 10:13 to 1:480 and fewer and fewer people have even had the chance to taste non-industrially produced salmon.

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. 2012). 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. 2012). 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. 2012)

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. 2012); 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. 2012).

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, 2012), which remarkable success (Miller. 2012).

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. 2012;2012:681016. Epub 2012 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. 2012 Aug;50(8):2696-702. Epub 2012 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. 2012 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. 2012;7(7):e41046.