Science Round-Up Seconds: DHA, Algae Oil, Fish Protein, Insulin Sensitivity, Fat Loss & Muscle Gain. Plus: Night Shifts & BPA = Pro-Carcinogenic From Breast to Prostate

It's somewhat ironic that Nurse's are one of the three high risk groups for breast cancer, because they work night shifts to help others. Who the other two groups are? Female military personnel and flight attendants on international flights.

If you did already listen to yesterday's installment of the Science Round-Up, you should actually be able to connect the dots between both, the first and second course of today's installment of the Science Round-Up Seconds, and the studies on the effects of DHA on fatty acid metabolism, as well as the fallacies of insufficient, interrupted, or irregular sleep Carl and I have been addressing, yesterday.

If all that does not ring a bell, I suspect you missed the show and have not had a chance to listen to the podcast (as usual the Science Round-Up starts in the 2nd hour of the show), yet. In this unfortunate case, I'd suggest you do at least start downloading the file while you take the first bite of today's two course menu ;-)

More things fishy from proteins with funky names to DHA and fish protein

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? Learn how to make the right fish choices here.

(Lane. 2013; Vikøren. 2013) -- Actually I wanted to title this one "Some Things Fishy", but then I remembered that there is already a SuppVersity post with this title, one I am still not able to make head or fin... ah, pardon tail of, by the way, because it clearly suggest that the consumption of oxidized fish oil is not a problem. Be that as it may, these are the SuppVersity Science Round Up Seconds, so the "more" does not refer to the said SuppVersity post on oxidized fish oil, but rather to the 70x* increase in the expression of a protein called Angiopoietin-like 4, which controls the availability of fatty acids for fuel I mentioned during the podcast (*the differential response for DHA was elucidated in a separate study on isolated rat hepatic cells, the general effect was however observed in a human trial, where all tested fatty acids, not just DHA, produced 11-12x ANGPTL-4 increases).

In view of the more of less undisputed benefits of having reasonable amounts of DHA (400mg) in your diet, it would obviously be nice if we could increase our intake of this relatively scarce omega-3 fatty acid in our diet, without having to resort  to fish and fish oil caps. A recently published overview of vegetarian dietary sources of omega-3 fatty acids by Katie Lane and her colleagues does however confirm what you've heard both Carl and me say on previous episodes of the SuppVersity Science Round Up, already.

The conversion of alpha linolic acid (ALA, the short-chain version of omega-3) from nuts (walnut) and seeds (flaxseed, echium) to DHA is literally zero. 

According to he researchers' review of the literature, only the ingestion of oils that were derived from micro-algae provide some, albeit preliminary evidence to support their usefulness as dietary source of DHA. The number of studies is yet relatively limited and "further research is necessary to evaluate optimal doses" (Lane. 2013) of respective supplements and/or food additives for "functional foods" (how I hate this word)

Micro-algae oils are not fish, though, and thus you would once more be missing out on the unique synergy only real foods have to offer: The fish proteins!

If you are not one of the many new visitors who have found their way to the SuppVersity only recently, the keyword "fish protein" should actually ring a bell... exactly! That's the stuff that has previously been shown to have astonishingly pronounced effects on glucose metabolism. Effect that have initially been observed in rodent studies and are not being replicated in human trials. Trials such as the one by Vikøren and his colleagues from the University of Bergen who report in their latest paper that was February issue of the British Journal of Nutrition that the provision of 3 g/d of a cabbed fish protein supplements for the first 4 weeks and 6 g/d for the last 4 weeks of a 2 months placebo controlled intervention study effectively and significantly

• 

  Table 1: Amino acid composition of fish, whey and casein protein (Hall. 2003; Vikøren. 2013)

  lowered the values of fasting glucose
• 2 h postprandial glucose and glucose-area under the curve,

• increased the important early insulin and 
• decreased the detrimental late insulin response to glucose ingestion 

• reduced the amount of  LDL-cholesterol (P< 0·05) and

• led to increases in lean (+0.8%) and decreases in fat mass  (-1.6%)

compared to the calorie-free placebo. Pretty impressive results, right? That's particularly true in view of the fact that neither the food intake nor the physical activity levels changed in the course of the 8-week intervention period.

What's that: Fish protein + fish oil? (Almost) whole fish, right!

Fish happens to be a way better source of taurine than the sperm of this Belgian Blue. There is in fact so little taurine bull sperm that it is "supplemented" with this amino acid in order to keep it fresh and stable and have it survive refrigeration. Apropos, you do remember that taurine can boost testosterone levels up to 250% - at least in rodents?

The obvious question therefore is: How does that work? The scientists don't provide a satisfactory explanation and to be honest, I have nothing more than a couple of half-assed hypotheses either. My best bet, and I am suggesting that despite the fact that a recent post of mine was entitled "Don't Judge a Protein By Its Amino Acid Content", would in fact be the amino acid content. If you take a look at table 1 it is obvious that the cod protein the scientists used in the study contained one amino acid you as a SuppVersity reader should by now be familiar with and neither whey, nor casein or any of the other standard proteins has to offer: Taurine!

Yet despite the fact that taurine has the potential to boost testosterone levels, increases insulin sensitivity and has in fact been shown to actively reduce body weight in a 2003 human study by Zhang et al. (Zhang. 2003), I am not sold on the idea that the relatively minor total quantity of taurine in the already low amount of fish protein (I mean 8g?) is the only reason for the non-negligible health benefits the scientists observed in their 10 male and 10 female participants (BMI 31-37kg/m²). Maybe it's another of those funky di-peptides you've read about in the context of the nutrient repartitioning effect of whey protein hydrolysate, only lately.

Regardless of what exactly it may be that facilitated the improvements in blood glucose management and the minor, but significant improvements in body composition, the health benefits you can derive from the consumption of cod protein make the notion of fish oil, let alone micro-algae oil supplementation appear even more retarded, when eating fish once or twice a week offers a way more natural and unquestionably more tasty solution to satisfy your DHA requirement.

Night shifts and breast, BPA and prostate cancer

There are two clockworks operating parallel in your body. The one in the brain has to be hacked by light exposure (learn more about "Sunlight a la Carte"), the one in your liver and other peripheral organs, on the other hand, can be (re-)set by specific feeding strategies, like Intermittent Fasting (learn more)

I simply assume that you have by now downloaded and listened to the podcast and are thus aware of what I said about the importance of rythmicity (if you did not really get the notion, I suggest you read up on the posts in the SuppVersity Circadian Rhythm Series to get a better grasp of the different clocks that are ticking in your body ;-) Exactly this kind of rhythmicity is continuously disturbed when you are either switching back and forth from day- to night-shifts or work the night-shift continuously and dare having a social life that's simply not compatible with sleeping all day and waking all night.

That the life of a nurse, for example takes it's toll on your health and precipitates not just the development of breast cancer (+36% after 30 years of rotating night shifts; Schernhammer. 2001), but colorectal cacers (+35% after 15 years of rotating night shifts; Schernhammer. 2003) and endometrial cancer (+47% after 20+ years and even +109% in obese women; Viswanathan. 2007), as well, has been debated ever since the early years of the 21st century.

With the recent publication of two meta-analyses the debate probably will not be over; and that despite the fact that even the less unsettling analysis by Kamdar et al. reports increases in breast cancer risk of +21% for women "with ever night-shift work exposure" (Kamdar. 2013).

"Subgroup analyses suggested that flight attendants with international or overnight work exposure and nurses working night-shifts long-term were at increased risk of breast cancer." (my emphases in Kamdar. 2013)

While the Kamdar study also included observational data, this 2nd meta-analysis, which was likewise published less than a week ago, included only case-control and cohort-studies yielding risk increases of +32% and +8%, respectively (Jia. 2013). Somethin else thatg may be worth mentioning is the fact that both, the studies the scientists ranked as "high quality" research, as well as the only existing study involving female military personnel observed even higher risk increases of +40%.

Despite methodological differences and slightly different outcomes of the two meta-analyses, both research groups do reach very similar conclusions stating that the evidence is still "weak", but does "support previous reports that night-shift work is associated with increased breast cancer risk" (Kamar. 2013) and that "large-scale epidemiological studies are needed" (Jia. 2013).

From breasts to prostates ;-)

Figure 1: Effects of 4-days of BPA injections at different dosages on systemic hormone levels (Castro. 2013)

I know the subheading sounds somewhat gross, but there are certain parallels. For one, there is the same need for large-scale epidemiological studies on the connection between BPA exposure and the development and malignancy of prostate cancer as it is the case with breast cancer and night shifts. On the other hand, BPS of which a recent study was now able to show that it messes with the aromatase and 5-alpha reductase activity in the prostate and can thus precipitate prostate cancer even in adulthood (Castro. 2013), is unquestionably relevant for the development of breast cancer, as well.

What's more, the reductions in 5α-R1 and 5α-R2 Castro et al. observed in their previously healthy, adult rodents after only 4-days of BPA injections at doses of 25, 50, 300, or 600 µg/kg per day and the concommitant increase in the expression of the third isoform of 5-α reductase (5α-R3) does not only precipitate cancerous growth, it's also a recently proposed as a biomarker of cancer malignancy. In conjunction with the quasi-reversal of hormones (see figure 1), the results of this study, which happens to be the first one to demonstrate such profound detrimental effects on mature mammals, should remind us of the fact gestation and early childhood are not the only time-points in our lives, we have to beware of endocrine disruptors.

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That's it for the Seconds and in case you are missing the information about fruits and vegetables, I will serve those tomorrow as part of the as of in fact short, but way more numerous "Short News". In case you are still hungry for more, I suggest you make take a slight detour to the SuppVersity Facebook Wall before you you sally into the weekend. There are a couple of appetizers waiting for you there:

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  "Does the Usefulness of Vitamin E Supplementation Depend on Your Activity Level?" While the marathon runners in the facebook study took only 50IU, 400IU is what most supplements have to offer as a minimum. Is that too much, for you? Do athletes need more? What about the hormetic response to exercise - it it even hormetic? (learn more)

  EGCG is an "anti-folate" - You still don't have to worry, nature has made sure that those who value the synergy of whole foods, or in this case drinks, won't be harmed (read more)
• LOW(!) doses of vitamin C & E (125mg & 50IU) don't diminish the benefits of exercise - On the contrary, in marathon runners that's enough to blunt the neutrophil damage (read more)
• Smart Kids = Lean Adults  - General intelligence as assessed in childhood has a significant and direct effect on adult obesity risk (read more)
• Valine, vanadium and oxygenated water - All useless for athletes. That's at least what the latest installment of the "A–Z of nutritional supplements" says (read more)

When you are done with those, it's about to start news fasting, for a couple of hours until tomorrow's morning news (for you probably today's late evening news) will be published on Facebook. Have a great "Post-Valentine's Day", everyone - I just  hope your spouses were happy with their presents ;-)


References:

• Castro B, Sánchez P, Torres JM, Preda O, Del Moral RG, Ortega E. Bisphenol A Exposure during Adulthood Alters Expression of Aromatase and 5α-Reductase Isozymes in Rat Prostate. PLoS One. 2013;8(2):e55905.
• Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr. 2003 Feb;89(2):239-48.
• Jia Y, Lu Y, Wu K, Lin Q, Shen W, Zhu M, Huang S, Chen J. Does night work increase the risk of breast cancer? A systematic review and meta-analysis of epidemiological studies. Cancer Epidemiol. 2013 Feb 8.
• Kamdar BB, Tergas AI, Mateen FJ, Bhayani NH, Oh J. Night-shift work and risk of breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013 Feb 12. 
• Lane K et al. Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature. Critical Reviews in Food and Science Nutrition. February 2013 [Epub ahead of print].
• Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA. Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8. 
• Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Fuchs CS, Colditz GA. Night-shift work and risk of colorectal cancer in the nurses' health study. J Natl Cancer Inst. 2003 Jun 4;95(11):825-8. 
• Vikøren LA, Nygård OK, Lied E, Rostrup E. Gudbrandsen OA. A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults. British Journal of Nutrition. 2013; 109:648-657.
• Viswanathan AN, Hankinson SE, Schernhammer ES. Night shift work and the risk of endometrial cancer. Cancer Res. 2007 Nov 1;67(21):10618-22.
• Zhang M, Bi LF, Fang JH, Su XL, Da GL, Kuwamori T, Kagamimori S. Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects. Amino Acids. 2004 Jun;26(3):267-71. Epub 2003 Dec 15.

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.