You Are What You Eat? Not Really! Rodent Study Shows Mice Are What the Salmon Ate That's in Their Chow

Image 1: Farmed Atlantic salmon Raised an fried with soy *yummy*

Health conscious as you are, you will probably make sure to get grassfed beef, pay extra for the delicious Kerrygold butter and ask your farmer whether the chicken that lay the eggs you are just about to buy were pastured or received the standard feed and tons of antibiotics... right? Ok, but do you know what the fish that's lying there right in front of you had as his last supper? No? Well, after reading today's SuppVersity news, you will probably give your fish monger the third degree... but one thing after the other.

We are what that what we eat ate!

In a soon to be published study in the British Journal of Nutrition, Anita R. Alvheim and her colleagues from the National Institute of Nutrition and Seafood Research, the Department of Biomedicine  at the University of Bergen in Norway, the National Institute on Alcohol Abuse and Alcoholism in Rockville, USA, and the Department of Biology at the University of Copenhagen in Denmark, report which astonishing (or should I say frightening?) downstream effects it can have when the fish farmer who supplies your local fish monger with salmon wants to save a couple of bucks and replaces the fish oil in the diet of his farm-raised Atlantic salmon with some cheap (and hip / at least among vegans ;-) soybean oil.

Table 1: Fatty acid composition of rodent chow (top) and change in fa content of salmon due to soy oil feeding (rel. fish oil fed salmon, bottom; Alvheim. 2013)

To elucidate the downstream effects of this practice, the researchers raised Atlantic salmon on either soy or fish oil based diets (250g of each added to the diet), slaughtered the animals, filleted them and used the fillets to prepare two calorically identical rodent chows. A practice, by the way which was not as easy as it may sound, after all the salmon that had received the soy-based diet was significantly fatter (33% fat in the fillet of the soy fed vs. 26% fat in the fish oil fed salmon), so that the scientists had to make up for the lack of fat. The 6-week old mice were then randomly assigned to one of the two experimental diets to which they had ad libitum access for 6 weeks.

As the data in figure 1 goes to show the rodents on the "soy-salmon" diet had a significantly elevated hepatic alpha linoleic acid and arachidonic acid (AA) content in the hepatic phospholipids. After 9 weeks on the diet, there was a trend towards increased body weight gains that reached statistical significance in week 15 - and that in the absence of statistically significant differences in energy intake. 

Figure 1: Linoleic acid, Arachidonic acid and Arachidonoylglycerol (endocannaboid) content of liver phospholipids (left, data expressed relative to fish oil diet group), body weight development (right; Alvheim. 2013)

Moreover, compared to the rodents on the diet that contained the "normal" salmon the rodents on the soy fed salmon diet had significantly lowered EPA and DHA levels in the phospholipid fraction of their liver, erythrocytes and white adipose tissue. This lead to an overall decrease of the omega 3-index from 23 to 16 and increased the relative abundance of n-6 highly unsaturated fatty acids from 19 to 39 % percent. The histological analysis of the adipose tissue did also reveal that the rodents who received the diets with the soy fed salmon exhibited significantly more of the so-called crown-like structures which are remnants of macrophage (immune cells) invasion into the inflamed and partly necrotic (=dead) adipose tissue. The presence of this structures is associated with major increases in local and systemic inflammation and their has been implicated as one of the major driving forces of obesity induced metabolic disturbances in mice and humans (Bremer. 2011). Furthermore the adipocyte size in the groin area (=inguinal WAT) was increased.

Figure 2: I must admit I did not check if AP got the data in this chart right, but if they did, the increase in AA and AA-related endocannaboids is only part of the problem and you better stick to grass-fed beef if you can't afford wild salmon.

Implications: Overall, the weight gain may be negligible, the intricate differences in the phospholipid structure of various cells and even the presence of the crown-like structures relatively harmless and still, with the overall increase in soybean oil consumption in the US (from 2.2% of the total energy to 7.3% of the total energy intake) and the constant decline of natural (not supplemental!) DHA and EPA in the diet of the average US citizen, in the course of the 20th century (Blasbalg. 2011), the indirect or "second feed" assault from all sorts of animal products may well be the literal "last straw that brakes the camels back". After all, there is accumulating evidence for a direct relation between the diet-induced increase in arachidonic acid derived endocannaboids like 2-arachidonoylglycerol (cf. figure 1) in rodents and humans and the modulating effects of dietary fat intake on the latter.

With the study at hand, Alvheim et al. show pretty conclusively that the effect of certain foods, specifically oils, can be "handed down" in the food chain an effect that is hitherto largely ignored by scientists and nutritionists. In conjunction with reports that show that the DHA and EPA content of Atlantic salmon is already on the decline, while the linolic acid content has increased from 1.1 g/100 g in 2005 to 1.6 g/100 g in 2010  (NIFES. 2011), this raises the question of whether salmon, which is still considered to be the go-to protein and fat source for health-conscious customers, has not already been turned into another Frankenfood and puts another emphasis on the importance of knowing not just what you eat, but also what whatever you eat ate or grew on... but the latter is, I guess a topic for another blogpost ;-)

References: 

• Alvheim AR, Torstensen BE, Lin YH, Lillefosse HH, Lock EJ, Madsen L, Hibbeln JR, Malde MK. Dietary linoleic acid elevates endogenous 2-arachidonoylglycerol and anandamide in Atlantic salmon (Salmo salar L.) and mice, and induces weight gain and inflammation in mice. Br J Nutr. 2013 Aug 10:1-10.
• Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011 May;93(5):950-62. Epub 2011 Mar 2.
• Bremer AA, Devaraj S, Afify A, Jialal I. Adipose tissue dysregulation in patients with metabolic syndrome. J Clin Endocrinol Metab. 2011 Nov;96(11):E1782-8. Epub 2011 Aug 24.
• Massiera F, Saint-Marc P, Seydoux J, Murata T, Kobayashi T, Narumiya S, Guesnet P, Amri EZ, Negrel R, Ailhaud G. Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res. 2003 Feb;44(2):271-9.
• NIFES. National Institute of Nutrition and Seafood Research. Research on nutrition;
  feed for fish and fish as food. < www.nifes.no/sjomatdata > retrieved Aug 14, 2013.

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.