Some Things Fishy: Oxidized Fish Oil Totally Benign!?Plus: The Inflammatory Side of EPA and Peroxide & Alkenal Levels in Commercial Fish and Vegetable Oils.

Image 1: Surströmming, a Swedish delicates is essentially rancid fish and it stinks exactly like that. Now, the results of a recent study show that the rancidity does probably not compromise the health benefits of the fish... so if you like it, go for it!

You know that whenever something is so (over-)hyped like fish oil or vitamin D that rings an alarm with me and when I hear "experts" on popular podcast say things along the lines of "as long as you take your fish oil that can compensate for a whacky diet", this is totally burning me up. Yes, there is conclusive evidence that for someone who has damaged his/her body by years and years of omega-6 over-consumption the inclusion of even "high" dose (I consider 5-6g high!) fish oil supplements can make sense, but NO, it will neither allow you to keep eating the same crap that has brought you to where you are at now, nor (and I think this is even more important for most of the SuppVersity readers) is there conclusive evidence that a healthy, active and lean human being is not way better off by limiting his total PUFA intake instead of popping grams of highly oxidizable n-3 fatty acids from fish oil caps.

Highly oxidizable? Yes! Dangerous? Surprisingly not!

A pros pos "highly oxidizable", the argument that polyunsaturated fatty acids (PUFAs) are readily oxidized not only in your body, but even at the shelves of your nutrition store, is one of the few possible caveats of fish oils supplementation even fish oil enthusiasts will acknowledge. After all previous animal studies have shown that diets rich (5%) in rancid (=oxidized) fish oils lead to increases in thiobarbituric acid-reactive substances (TBARS) levels and elevate liver specific transaminases, as well as the alkaline phosphatase (ALP) levels in the plasma of rats (detrimental effects which can by the way be ameliorated by taurine supplementation, cf. Hwang. 2000). The results of a recent study by Inger Ottestad and colleagues from Norway may thusly surprise the "pro-fish oil"-faction about as much as they surprised me (Ottestad. 2011): The ingestion of 8g of oxidized (peroxide value: 18mEq/kg; ansidine value: 9) fish oil (1.6g EPA+DHA) did not have any unfavorable short term-effects in previously healthy individuals.

Figure 1: Serum (left, 8-iso on secondary axes was measured in urine) and erythrocyte (right, GPx on secondary axes) markers of oxidative stress in 68 healthy subjects who were randomly assigned to ingest 8g of "fresh" fish oil, oxidized fish oil or high oleic-acid sunflower oil per day for before (pre) and after (post) the 7 week intervention (data adapted from Ottestad. 2011)

If you take a closer look at the measured levels of serum (4-hydroxy-2-hexenal: 4-HHE, 4-hydroxy-2-nonenal: 4-HNE, alpha-tocopherol,  high-sensitive C-reactive protein: hsCRP and 8-iso-PFG2a, the latter in urine) as well as erythrocyte (total GSH, 4-hydroxy-2-nonena: GR, CAT and glutathione peroxidase: GPx) markers of oxidation before and after the 7-week intervention (cf. figure 1), it is quite obvious that there were no statistically significant oxidation-related changes in the concentrations of the measured markers of oxidative stress, of which the scientists state that they are the current, yet debatable, "gold standard" for in vivo studies.

Figure 2: Changes in n-3 and n-6 levels and the n-6/n-3 ratio (small graph) in the course of the study period (data calculated based on Ottestad. 2011)

It is thus not really surprising that both fish oil groups experienced virtually identical (and highly favorable) -50% reductions in the ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids. Moreover, ...

[a]fter 3 and 7 weeks of intervention, the plasma level of EPA, docosapentaenoic acid and DHA were significantly increased in both fish oil groups compared to the HOSO group, but no significant difference in EPA, doc-osapentaenoic acid and DHA between the FO and oxFO groups was observed.

The scientists are thusly right to conclude that their results do not support the often-heard hypothesis that higher intakes n-3 long-chain fatty acids could increase in vivo lipid peroxidation and more importantly, that ...

[...] the content of hydroperoxides in fish oil supplements, even with a PV that exceeds the European Pharmacopeia for marine n-3 oils, does not apparently influence the plasma level of n-3 FA.

With regards to the obvious differences to previous animal studies, the scientists state that secondary oxidation of hydroperoxides, which are then absorbed in the intestine has until now been observed in animal and cell studies. In view of the relative short duration of the study and the reliance on healthy subjects, it is also questionable whether identical results would have been achieved, when sick patients (the usual customer group at least for the pharma-grade n-3 supplements) had been treated with the same product for years.

Oxidized fats in fish oil and beyond

It is also worth mentioning that Ottestad et al. are not sure, whether their "aritifically oxidized" fish oil (oxidation was achieved by sparkling pure oxygen through the oil for 20 min twice a day for 21 d) was an appropriate model for commercially available (oxidized) fish oils. After all, there could be major differences in the composition of the oxidation products, when the oils go rancid over months or get damaged by heat etc. While I obviously cannot answer this question without setting up my own lab, I can however tell you that another recent study by Halvorsen et al. who examined the peroxide and alkenal (one of the major products of secondary oxidation) content of fish and vegetable oils, found average peroxide levels in 33 commercially available fish oil products (mean PV: 3.61mEq/kg) that were ~500% below the ones of the oxidized fish oil (18mEq/kg) in the Ottestad study.

Figure 3: Mean peroxide and alkenal values of 33 commercially available fish and 35 vegetable oils (Halvorsen. 2011).

In this regards, fresh vegetable oils, obviously are way in front, as the data from a study by Bente Lise Halvorsen and Rune Blomhoff clearly shows, that they have lower peroxide and much lower alkenal levels than fish oils (cf. figure 3). Interestingly, vegetable oils are also less prone to being oxidized during storage, something Halvorsen and Blomhoff conclude based on the absence of the "negative correlation (r=−0.557, p<0.001) [...] between the number of days until expiry and the PV [peroxide value]" they observed in the marine omega-3 oils.

Figure 4: Peroxide (PV in mEq/kg) and alkenal (in nM/ml) levels in fresh vegetable oils and after being heated for 25 minutes at 225°C in an oven (data adapted from Halvorsen. 2011); solid red line - maximal peroxide value for olive oils, dotted red line - maximal peroxide values for fish oils as suggested by Turner et al. (Turner. 2006)

Contrary to fish oils, which are usually taken "fresh" and in a capped form, the main fate of vegetable is however to be (ab-)used as cooking / frying oils. During the heating process, the amount of secondary lipid oxidation products, the alkenals, doubles or quadruples depending on the type of oil (cf. figure 4). In that, it may at first seem counterintuitive that, when the scientists heated the samples for 25 minutes at 225°C in an oven, the amount of primary oxidation products was slightly reduced in most, but not all (e.g. soy bean oil) of the 11 vegetable oils. If you do yet take into consideration that the latter are the "raw material" for the secondary oxidation products, it becomes quite clear that this is not a desirable process ;-)

Image 3: Extra virgin olive oils (EVOOs) have generally higher peroxide values than the cheap refined stuff, and yet, EVOOs and not refined oils have been shown to exhibit numerous health benefits.

Putting peroxide values (PV) into perspective: All potential health hazards aside, it may be interesting to know that the general "rule of thumb" says that a fat is rancid when the PV is about 10 meq/kg (the fish oil in the study with PV=18 was thusly "rancid"). A fresh and refined product on the other hand should have PV below 1 meq/kg (Gunstone. 1996). That being said, it may surprise you that for high quality extra virgin olive oils, the PV limit is 20meq/kg, while for "regular" olive oil it is only 10 meq/kg. If you know look at studies related to the health benefits of refined vs. extra virgin olive oil, you will have to admit that - quite obviously - fish oil apparently is not the only oil, where increased peroxide levels do not negate the beneficial health effects of the oil.

So, if pure vegetable oils are generally "fresher" than fish oils does that mean that as long as you do not heat them, they are the better choice? No, they are not! I mean, look at the research that is out there... the abundance of n-6 fatty acids in the "healthy" vegetable oils that are getting pimped especially by the US government, is at the heart of an epidemic of which the authorities still claim that it was caused by high cholesterol levels. Instead banning all saturated fats from YourPlate (which should never look like the governments MyPlate ;-), you should rather incorporate more coconut oil and saturated fats from butter, beef etc. into your diet. Select (vegetable) oils that are relatively high in mono-unsaturated fatty acids, like extra virgin olive oil (don't care about its high peroxide value, cf. red box above) and try to reduce the amount of n-6 fats you ingest - you will get more than enough even from grass-fed meats, olive and other oils and any processed foods that may still be part of your diet, anyway.

Image 4: Not all Omega-3 are created equal. We know for some time that DHA (not EPA) is what your brain needs and a recent study from Norway suggest that eicosapentaenoic acid (EPA) is actually pro- not anti-inflammatory at a cellular level. It may yet well be that this in turn triggers a beneficial hormetic response which would support my "fish oil = exercise in a pill hypothesis"

Although this is not directly related to the topic of oxidation I still want to add that another study appears to confirms my long-cherished skepticism towards EPA (most fish oils have a 2:1 EPA to DHA ratio), which, as a recent study from Norwegian scientists shows (Myhrstad. 2011), is not really "beneficial super-antioxidant" people are led to believe. In their trial the scientists fed 14 healthy female volunteers test meals. The cakes the participants ate were enriched with either flaxseed, cod liver or coconut oil and the intention of the study was to elucidate differential effects of meal fatty acid composition on inflammatory markers. Not to my, but probably to the scientists surprise the "evil" saturated fat from the coconut oil turned out to be similarly benign as the flaxseed cake. Only the EPA-laden cod liver oil cake produced a statistically significant increase in IL-8 mRNA levels 6h post ingestion. Similarly, incubation of peripheral blood mononuclear cells with EPA, yet not ALA lead to >3x increase in IL-8 and >2x increases in IL-6 mRNA expression.

While I am not quite sure what to make of these observations, these results stand in line with previous studies reporting differential effects of EPA vs. DHA rich fish-oils, where across the board, the DHA appeared to be the major driving force of the beneficial health effects people hope to be getting from their fish oil caps (e.g. brain health, Engström. 2009).

Fish oil caps can be a good addition to this regimen specifically for those who are just about to start out on a low omega-6 diet to offset the skewed n-6 to n-3 ratio (something that takes its time). They are yet by no means obligatory for someone who eats fish on a regular basis and invests the extra bucks into grass-fed beef and eggs from pastured chicken. If you thusly satisfy your (anyway low) dietary DHA requirements... and most importantly, taking fish oil will not compensate for eating shitloads of processed foods and lack of exercise, even if the aforementioned pro-inflammatory effects of EPA support my previously uttered hypothesis that fish oil has some resemblance to "exercise in a pill".

Pimp My Olive Oil! When Virgin is not Phenol-Rich Enough: The Pharmacokinetics of Phenol-Enriched Virgin Olive Oil.

Image 1:  "If we have not somehow pimped it, it can never be good enough!" appears to be one of the credos with which mankind approaches almost every health-remedy nature has provided for us. In the past this approach was not particularly healthy, though... is phenol-enriched olive oil going to be the exception to the rule?

Being the health-conscious person you obviously are (why else would you visit the SuppVersity ;-), chances are that olive oil, or, to be specific, extra virgin olive oil is one if not primary source of of mono- and polyunsaturated fats in your diet. But do you actually know why? I mean why olive oil? And why extra virgin? What? "Mediterranean diet", "high MUFA content", "lower incidence of coronary heart disease and cancer"? All right, you have done your homework on olive oil, but what about the "extra virgin"? The polyphenols, right. The phenolic content is in fact what distinguishes a "good" olive oil. The phenolic alcohols, the secoiridoid derivatives, the phenolic acids, the lignans and the flavonoids in concert have been reported to have anti-oxidant, anti-inflammatory, anti-atherogenic and anti-carcineogenic properties and are probably as, if not more important for the beneficial health effects of the Mediterranean gold than its fatty acid profile (Covas. 2007; Covas. 2008).

So, if those polyphenols are the "active ingredients" in olive oil, wouldn't it be nice if we had an oil that had even more of these beneficial healthy secondary plant metabolits in our oils, right?

Now we have tons of polyphenols, but does that make a difference?

The thought, that a souped up version of the already phenol-rich virgin olive oil would be an even more potent health promoter must have occurred to a group of researcher from Spain, as well. Back in 2010 already, Manual Suárez and his coworkers published a paper in the Journal of Argiculture and Food Chemistry in which they describe the development of a "phenol-enriched olive oil with phenolic compounds from olive cake" (Suárez. 2010). In essence, the scientists just put back some of the pulp (an extract to be precise) that is produced when the oil is squeezed from the olives into the end-product. In a more recent study the scientists did now try to evaluate how much of these (additional) health promoters in 30ml of regular virgin olive oil (VO) and the enhanced virgin olive oil (EVOO) actually make it into the blood of 16 (8 men, 8 women) healthy subjects in a randomized, controlled, cross-over trial (Suárez. 2011).

Figure 1: Compositional differences (phenol-enriched vs. standard virgin olive oil) in polyphenol content (data calculated based on Suárez. 2011)

If you take a look at the compositional differences between the regular and the "phenol-enriched" virgin olive oil, it is quite obvious that, from a mere quantitative point of view, Suárez' product with on average 3.3x more secondary plant metabolits should be the more potent health promoter. After all, numerous previous studies have shown that those olive oils with (naturally!) particularly high phenol-content exhibit the most pronounced beneficial health effects (Samanego Sanchéz. 2007). This would yet require adequate absorption of the respective compounds from a now obviously more dense solution, which, according to the results of this study, does not seem to be the case for all compounds - and more importantly, all subjects:

The in vivo study showed that the concentration of fourteen of twenty-four compounds detected was higher in the plasma samples from the EVOO than after ingestion of VOO. Among these, two of them, hydroxytyrosol sulphate and vanil-lin sulphate, were statistically significant in attending their pharmacokinetic parameters, demonstrating the suitability of enrichment. In general, a displacement of the time to reach the maximum concentration is observed in the samples, which indicates that more time is needed to absorb the higher phenolic content. However, inter-individual variabilityin the concentration of the plasma phenol metabolites shows that it is difficult to show statistically significant differences between the VOO and the EVOO.

The scientists thusly conclude that the "metabolism of phenols is affected first by the individual". So until we actually know which influence these are, the label "phenol-enriched" on olive oils and other products has little meaning for you as an individual. And even if you belong to the "lucky" high-absorbers, only two, namely vanillin sulphate and hydroxytyrosol sulphate will reach what the scientists call "pharmocokinetic" levels, if you ingest two tablespoons of the super-potent "phenol-enriched" virgin (and still relatively natural) olive oil.

Figure 2: Changes in total antioxidant activity (TAA) of experimental oils subsequent to heat treatment (from Pellegrini. 2001)

Note: Common Internet wisdom would suggest that you have to be particularly cautious with those "phenol-enriched virgin olive oils", when respective products hit the market (and I bet this won't take long). After all, you will all have heard how heating those oils damages the healthy polyphenols - and while that may to some extend be the case, a 2001 study by Nicoletta Pellegrini et al. found that the total antioxidant value of olive oil does not only increase with increased polyphenol content, but that those polyphenols are also "stabilizers of R-tocopherol during olive oil heating, thus contributing to the nutritional value of cooked foods" and "the prevention of antioxidant activity decay in olive oil during realistic heating conditions" (Pellegrini. 2001), which ranged from 30min at 160°C to 120min at 190°C. The latter happens to be at the upper end of the regular deep-frying temperature and would thus suggest that the commonly heard recommendation not to use extra virgin olive oil for frying is not valid, at least when we focus exclusively on its total antioxidant capacity as measured by Trolox essays (cf. figure 2). In that it should be mentioned that, with its relatively high content of highly oxidizable omega-6 fats, olive oil still isn't the "ideal" frying oil - notwithstanding that frying does not constitute the healthiest way of preparing your food anyways ;-)

And though a recent study has shown that the latter conjugates with LDL and thusly protects it from oxidative damage (González-Santiago. 2010), it remains to be verified whether the consumer variety of the olive oil in this study will actually provide any health benefits. And this is particularly true in view of the fact that the food giants will, as they already do it in the case of "normal" virgin olive oil, minuscule amounts this probably expensive ingredient into their otherwise unhealthy convenient products, just to be able to put the highly marketable "contains phenol-enriched virgin olive oil" on the label... but, hey! I guess, this is just the never-ending story of complete nutritional idiocy ;-)

On Short Notice: Nucleotide Supplementation Increases Performance & Fortifies Immune Response. Plus: Oleic Acid Increases, SFA Lowers E2, Testosterone & DHT Binding

Are nucleotides a useful supplements for intensity maniacs and can olive oil reduce your free testosterone levels?

If you have been visiting the SuppVersity for a while now, you were probably surprised to see that the "Short News" (aka "On Short Notice") are back. The reason, I changed my mind and reintroduced this assembly of short news items is that I realized that there is an intemediate category of news and infos between the very short Facebook news that (a) disappear in the oblivion of the SuppVersity Facebook Wall, (b) don't allow me to post graphics that would illustrate the study results and (c) still take some time to write and the detailed analysis in the "original" SuppVersity articles.

So, if you disagree and can give me a good reason why I should not post news compilations like the one at hand more regularly, speak now or forever hold your peace ;-)

Nucliotide supplementation counters immune suppressive effects of exercise

(Ostojic. 2013) - I think I mentioned a similar study a couple of weeks ago in the SuppVersity Facebook News, but since this most recent investigation into the ergogenic effects of the small organic nitrogen-based combinations of a five-carbon sugar and a phosphate group that

• form the building blocks of nucleic acids, such as DNA and RNA, and 
• participate in cellular signaling and metabolism

deals with in young, healthy, fit men and their response to the provision of a supplement that looks similar to something you are probably goint to see on the market pretty soon, I thought it may be interesting enough to make it into this "news" article-format.

Figure 1: Illustration of the molecular structure of nuleotides (Sadava. 2000)

The supplement we are talking about is a combination of different nucleotides, i.e. cytidine 5′-monophosphate, uridine 5′-monophosphate, guanosine 5′-mono-phosphate and adenosine 5′-mono-phosphate from partially purified (90%) germinated barley seeds extracted during sporulation and the reason it's worth knowing what was in it, because it was able to ...

• Want a quick performance fix? Use sodium bicarbonate | learn more

  significantly increase time to exhaustion (+7%)
• ramp up serum levels of immunoglobulin A and
• elevate the NKC cytotoxic activity

in the blood of the 14 recreationally active participants (age 22; BMI 24kg/m²; body fat 11%) who participated in a standardized incremental exercise test on the treadmill ("Run till you drop") after taking 50mg/day of this product for 2 weeks.

Oleic Acid Increases E2, Testosterone & DHT Binding

Not from Greece, the land of olive oil and eve's cheese, but from Spain comes a study that links Oleic acid, the mono-unsaturated fat from Olive oil to increases in SHBG. The researchers from the Universitat Autònoma de Barcelona analyzed the lab reports and nutrition data of a total of 315 men and observed that

"SHBG serum levels were significantly higher in subjects using olive oil for cooking in comparison with subjects using sunflower oil. The SHBG levels correlated positively with MUFA (p < 0.001) and negatively with saturated fatty acids (p = 0.003)." (Sáez-López. 2013)

Based on multiple regression analysis of the data, the scientists calculated that the amount of MUFA in the subjects' diets accounted for 20.4% of SHBG variance. Despite the fact that this means that your MUFA intake determines "only" 20% your SHBG levels, the data in Figure 1 (left), clearly indicates that these 20% show pretty significant correlations with important health markers.

Figure 2: Correlation between SHBG levels and BMI, MUFA intake (in % total fat) and fasting blood glucose - left; correlation between phospholipid MUFA and SFA content and SHBG - right (Sáez-López. 2013)

In order to elucidate the underlying mechanisms, the scientists conduced an additional in-vitro study, in the course of which Sáez-López were able to confirm that oleoyl-CoA, a metabolite that's produced, when oleic acid is metabolized, downregulates PPAR-γ in the liver (HepG2 cells).

As a SuppVersity veteran, you'll know that any reduction in PPAR-gamma in the adipose tissue will result in a decreased propensity of fat storage (read up on it). In the liver, PPAR-gamma is  responsible for the production of SHBG, as well. In view of the fact that SHBG binds and deactivates* androgens and estrogens (*this is not essentially correct for all tissues!), your MUFA intake could thus be one of the set-screws that determine the level of unbound sex-steroids in your blood.

With 60-80% olive oil is one of the best sources of oleic acid and this is not a reason to stop consuming it - irrespective of T-binding (read more)

Bottom Line: Based on the currently available evidence it appears as if nucleotide supplements could have a future as immune and performance booster for intense training athletes.

Despite the fact that it is unlikely that there will be any side effects, (a) the increased immune activity, which could be a problem for people with auto-immune disease and (b) the non-existence of scientific evidence to support their long-time efficacy (and safety), I would wait and see how things develop before investing significant amounts of money in supplemental RNA / DNA precursor.

Something very similar is true for results of the Sáez-López study that investigated the "SHBG raising" effects of oleic acid. In view of the negative association between SHBG levels BMI and fasting blood glucose, which have, by the way, been observed in previous studies: Phillips & Gerald, for example, observed a significant negative correlation between SHBG and the waist / hip ratio in 55 obese men aged 21 to 70 (Philips. 1993). And while SHBG binds testosterone the small change will not render all your testosterone useless, so that you don't have to be afraid of sudden olive oil induced anti-virility effects ;-)

References:

• Ostojic, Sergej M., Kemal Idrizovic, and Marko D. Stojanovic. "Sublingual Nucleotides Prolong Run Time to Exhaustion in Young Physically Active Men." Nutrients 5.11 (2013): 4776-4785.
• Phillips, Gerald B. "Relationship between serum sex hormones and the glucose-insulin-lipid defect in men with obesity." Metabolism 42.1 (1993): 116-120.
• Sadava, D. et al. Life: The Science of Biology, 9th ed. 2009
• Sáez‐López, Cristina, et al. "Oleic acid increases hepatic sex hormone binding globulin production in men." Molecular nutrition & food research (2013).

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

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

Since this post is already lengthy enough, I will spare you how saturated fatty acids have long falsely been accused as the sole driving force of the western obesity epidemic and how the tides appear to be slowly yet steadily appear to be turning, as scientists delve deeper and deeper into the interactions of the total fat content in the diet, its fatty acid composition and the interaction of both with the two other macronutrients and their specific forms and get right to the study at hand. A study that appears in the current issue of the Journal of Lipid Science and deals with the first of the aforementioned interactions. The one that focuses on the total fat content and the individual fatty acid make-up of the diet (Enos. 2012).

Fat shoot out: Saturated vs. mono vs. PUFA

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

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

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

Figure 1: Fatty acid composition (left) and their sources (right) that were used in the different diets the rodents were fed for 16 weeks (based on Enos. 2012)

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

Figure 2: Body composition (left), adipocyte size (right) and fat pad weight (inset) of the rodents at the end of the study period (Enos. 2012) Values not sharing a common letter (abc) differ significantly over time within the given diet treatment (P≤.05)

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

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

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

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

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

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

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

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

... mimics, as the researchers point out, "most closely" (Enos. 2012) the standard American diet (SAD). And the result is obvious: Diabesity!

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

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

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

Figure 3: Serum IL-6, MCP-1, adiponectin and leptin levels, TNF-alpha mRNA expression in the adipose tissue (left), adipose tissue sample form the rodents receiving standard chow, the SFA-12% and the SFA-24% diet (Enos. 2012). The fat cells of the SFA-6% animals looked similar to those on the SFA-6% diets.

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

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

Figure 4: Blood glucose and insulin levels of the mice over the course of the study period (Enos. 2012)

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

"The 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity (absolute fat mass), macrophage infiltration, and IR [insulin resistance]." (Enos. 2012)

Figure 5: Total  cholesterol (TC, top) and LDL-C to HDL-C (bottom) ratios (Enos. 2012)

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

"Although the 24%-SF diet increased adiposity and produced IR, it did not significantly increase macrophage infiltration, it led to a lesser degree of AT inflammation, and it did not raise the TC/HDL-C ratio." (Enos. 2012)

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

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

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

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

References:

• Enos RT, Davis JM, Velazquez KT, McClellan JL, Day SD, Carnevale KA, Murphy EA. Influence of Dietary Saturated Fat Content on Adiposity, Macrophage Behavior, Inflammation, and Metabolism: Composition Matters. J Lipid Res. 2012 Oct 28.

The Healthy Taste of Olive Oil. Would the Flavor Be Enough to Induce At Least Some of Its Health & Satiety Effects? Plus: Cholesterol Control - Pomace vs. Refined Olive Oil

What about an EVOO perfume, then?

I know, it sounds crazy, but in view of what you've learned in previous articles here at the SuppVersity about sweet taste receptors (learn more) and their far-reaching influence on our metabolism, it does not appear to far-fetched to assume that there is a receptor that "tastes" the flavor-active compounds of olive oil that's responsible for some of its beneficial health effects - right?

I guess, Sabine Frank and almost a dozen of other scientists from Germany and Austria must have had a similar idea, when they came up with the research question of their most recent study.

Olive oil flavored yoghurt?! Really?

I suppose, olive oil flavored, or, more specifically, low-fat yogurt mixed with a fat-free aroma extract from olive oil may not sound appealing to the average Western customer, but it would certainly deserve the label "functional food":

Figure 1: Only the olive oil enhanced yogurt will also enhance the activity of the frontal operculum (Frank. 2013)

As you can see in Figure 1, it's a functional food that has a statistically highly significant effect on the cerebral blood flow in the frontal operculum 30 and 120 min after a meal: This and the increased activity in the anterior insula of which the scientists found that it correlated positively with the postprandial change in bloos glucose change in the 11 healthy male subjects of the study, clearly suggest: The taste of olive oil alone has significant effects on the blood flow in parts of the brain that are involved in the control of energy intake and metabolic rate.

"What is the "frontal opercular" and why would I care about its blood supply?"

If the subheading to this paragraphs describes what you are thinking right now, it's about time to take a look at the little information we have about the frontal operculum:

• 

  Suggested read: "Pimp My Olive Oil! When Virgin is not Phenol-Rich Enough: The Pharmacokinetics of Phenol-Enriched Virgin Olive Oil." | read more

  We know from previous studies that the frontal operculum (FP) is sensitive to food intake.
• The study at hand shows that the FP does not care about caloric values (the yogurts were isocaloric).
• In task-related studies, the frontal operculum as part of the primary taste cortex, has shown pronounced activation to visual food cues and anticipation of food intake.
• The activation of the frontal operculum appears to control the "this smells good" or "this looks good, I must have it" response that makes weight loss so difficult.
• There is a telling relation between the sensitivity of the frontal operculum and the BMI of a person (Batterink. 2010; Yokum. 2011)
• Earlier fMRI studies showed that oral delivery of a drop of fat leads to an immediate increase in insular and frontal opercular activity, which suggests that there are "fat taste receptors" somewhere in the oral cavity or digestive tract that are wired to the the frontal perculum (Small. 2012).

Now, in context of the results of the study at hand, it is obviously the last of these points, which is particularly interesting. The discovery Frank et al. made would after all suggest that we can get satisfactory "fat effect" without the fat - simply by having the right "aroma."

Figure 2: Modulating effect of the minor components of pomace olive oil (POMACE) on lipid composition in 10 healthy young men (Cabello-Moruno. 2013) - severs as illustration for the importance of the "non-fat" components for our health.

Frank et al. also point out that the fact that they measured the CBF not immediately but 30 min and 120 min after the consumption of the yogurt would make it quite unlikely that they had mistaken an acute aroma response for what they believe is the "association with fat" - in other words, the researchers believe that the ingestion of the olive oil flavor components "modifies later responses to achieve an appropriate sensory control." Effects just as we know them from glucose and artificial sweeteners which "prepare" the body to release insulin.

Per capita consumption of vegetable oils and fats in selected European countries in 2009 (Eurostat. 2011)

Bottom line: I guess it is too early to say, whether and what kind of applications the said olive oil extract could have in the future. What the study does however show is that focusing on macros and even micronutrients, only, is insufficient.

In fact, the "ideal" diet, with the perfect macros and 100% adherence could in the end turn out to produce inferior results to a "sub-optimal", but tasty diet with olive oil and other aromas triggering all-sorts of still to be elucidated beneficial downstream effects on our physiology and psychology.

Reference: 

• Batterink L, Yokum S, Stice E. Body mass correlates inversely with inhibitory control in response to food among adolescent girls: an fMRI study. Neuroimage 2010;52:1696–703.
• Cabello-Moruno R, Martinez-Force E, Montero E, Perona JS. Minor components of olive oil facilitate the triglyceride clearance from postprandial lipoproteins in a polarity-dependent manner in healthy men. Nutrition Research. Oct. 2013 [accepted manuscript]
• Small DM, Green BG. A proposed model of a flavor modality. In: Murray MM, Wallace MT, eds. The neural bases of multisensory processes. Boca Raton, FL: 2012
• Yokum S, Ng J, Stice E. Attentional bias to food images associated with elevated weight and future weight gain: an FMRI study. Obesity (Silver Spring) 2011;19:1775–83.

On Short Notice: 250% More Testosterone From Oleuropein in Olive Oil? Obese Kids, TV, Twinkies & Tortilla Chips, Vitamin D Supplementation That Works, Coffee, Green or Gomchui Tea as Fat Blocking Orlistat Alternative and More!

Image 1: A tablespoon of olive oil is probably not enough to boost your testosterone levels, right? Probably not, at least not by 250%, I should say.

Another Saturday, time is flying by and we have no time to waste, because YOU will have to dig trough a whole host of pretty long and (hopefully) interesting "On Short Notice" news, today! So let's get to business and start out with the surprising testosterone boosting corticosteroid normalizing effects of a bitter phenol in extra virgin olive oil most of you will probably be consuming on a daily basis without even knowing its name - Oleuropein. When we are through with the human equivalent dosage calculations the scientists obviously forgot to do, we will make a detour to one of those problems that are particularly dear to my heart, childhood obesity and how watching TV and eating fatty and sugary foods make a dynamic duo that can increase your (grand-)son's, (grand-)daughter's, nephew's and niece's risk to become obese by up to 30%. We will then use our flux-compensator (edit: I used the term that's used in the German version, i.e. "flux compensator" before, but edited it after Gary pointed out that the DeLorian in the original US version had a "flux capacitor" and a brief "research" made it obvious that this is a mistake of whoever translated the term for the original Back to the Future movies) and jump forward in time and see that your hopefully by the non-obese daughters and nieces can reduce their risk of visceral obesity and thus increased mortality even if the just wash the dishes, take the dog for a walk and use the stairs instead of the elevator.

Before we are eventually going to have a cup of gomchui tea, to evaluate if we can stand the taste so that we could ingest the 2-3 servings it would probably take to negate the negative effects of an occasional fatty slip on our diet, I will yet invite you to take yet a look at two studies from Saudi-Arabia, in which the researchers showed quite convincingly that vitamin D can actually have all those magical anti-obesity effects that it is hailed for, if... yeah, if you put the active calcitriol instead of its precursor cholicalciferol into the fatty chow of rodents. Sounds good? Well let's go, then!

• 

  Figure 1: While the results of the study, as well as the implications are impressive, the statement that one would get the respective human equivalent dose from "normal dietary intakes" is questionable, to say the least (see text for details) - and still the results of the study at hand only add to the nutritional value of the "liquid gold of the Mediterranean" with its proven antioxidant, antiinflammatory, antiageing, anti-viral, anti-microbial, anti-cancer, anti-aetherogenic and skin protectant effects (cf. Omar. 2010)

  Olive oil contains natural anabolic... well, sort of; at least according to research from the Laboratory of Nutrition Chemistry at Kobe Women's University in Japan, oleuropein, a phenolic compound in extra virgin olive oil did calm down the potentially catabolic corticosteroid overactivity in male rats fed a high protein (40%; from casein) diet (Oi-Kano. 2012). Allegedly, this alone does not yet make it an "anabolic", but with it's concomitant, but highly protein-dependent effect on the testosterone production in the testes of the male Sprague Dawley rats (see figure 1 - top, right), the ameliorative effect on the high corticosteroid expression on the high protein diet (+100% serum corticosteroids in the 40% vs.10% casein group w/out supplementation) and the consequently increased nitrogen balance (=higher net retention of protein) oleuropein aglycone does have much more of a natural anabolic than 99.9% of the expensive testosterone boosters out there.
  The increased secretion of noradrenaline and adrenaline (see figure 1 - top, right), as well as the downstream effect on the expression of uncoupling protein UCP-1 in BAT and the subsequent increase on thermogenesis should contribute to the "body recompositioning" effect of oleuropein, of which Oi-Kano et al. state that they will be particularly pronounced on a "high-fat diet, i.e., 30% fat diet" (Oi-Kano. 2012).
  The fact that humans have hardly any BAT is yet not the only problem, when it comes to the real-world significance of these results. With 10.3mg per rodent per day, i.e. 41mg/kg per day (human equivalent dose 6.68mg/kg), the "effective dose" of regular extra virgin olive oil would be unrealistically high, even if we base our estimate on the same (unpublished) data Oi-Kano et al. use in the discussion of their results and assume that there are 104 mg/kg oleuropein aglycone in extra virgin olive oil. The scientists do yet obviously believe that 5L of olive oil (80kg x 6.67mg/kg body weight divided by 104mg/L olive oil) would be a "normal dietary intake of extra virgin olive oil" - a statement that sounds even more laughable, when we use data from a study by Owen et al. which found that the oleuropein content of extra virgin olive oil ranges from 2.3 to 9.0mg/L (Owen. 2000), with higher levels of oleuropein in bitterer EVOOs (Gutiérrez-Rosales. 2003), or base our estimates on another study from Oi-Kano et al. in which they measured an oleuropein aglycone content of ~19mg/kg extra virgin olive oil (actually we would even hate to make up for the lower density of olive oil and divide that by 0.91 to convert it mg/L). And let's be honest in view of the sheer amount of studies investigating the beneficial effects of extra virgin olive oil in animals and humans, I doubt that a +250% testosterone boosting effect of "normal dietary intakes of extra virgin olive oil" could actually have remained unnoticed...
  It also remains to be seen if olive leaf extracts provide a better alternative. In 2008, Jemai et al. report that the Chemlali olive leaves they used in their rodent study, yielded 4.32 g oleuropein and 3.82g oleuropein aglycone per 100g dried leaves (Jemai. 2008). In view of the fact that the yield will necessarily depend on both the cultivar an the extraction method, you should thus make sure that any extract you buy has a standardized content of oleuropein / oleuropein aglycone. Moreover, if you are mainly interested in the better-established antioxidant, antiinflammatory, antiageing, anti-viral, anti-microbial, anti-cancer, anti-atherogenic and skin protectant effects of olive oil (cf. Omar. 2010),  5L /day are not necessary, anyway ;-)

• 

  Figure 2: Vicious cycle of childhood obesity (top); childhood obesity trends - state rates (data according to Childhood Obesity Action Network. 2009)

  In children under the age of 10 television watching increases risk of obesity by +30% This is the alarming result of a subgroup analysis (N = 1,696 schoolchildren) from the IDEFICS study, a large scale epidemiological study that involved a total of 15,144 children aged 2-9y from Italy, Estonia, Cyprus, Belgium, Sweden, Germany, Hungary, and Spain. Contrary to comparable analyses, which tend to simply correlate obesity data with data from a questionnaires on the total daily or weekly TV consumption, the Lissner study had a more sophisticated approach towards "TV watching" which included (a) the kids habitual television exposure time, (b) television viewing during meals, and (c) whether or not the children had a televisions in their bedrooms.
  After correlating these data with additional information about taste preferences, Lissner et al. found that all three aforementioned parameters, i.e. total TV consumption, watching TV during meals and having a TV in their room, were associated with profound (21-30%) increases in obesity risk.
  The actual novelty of these results is yet that all these TV watching behavior correlated (in most cases monotonously) with the propensity to eat sugary and/or fatty foods - and that despite the fact that the same kids who were eating nothing but chips and dingdongs, when they were sitting in front of the boob tube did not show similar preferences for fatty and sweet in the contextual different testing sessions all 1,696 kids had undergone.

• 

  Figure 3: A few steps a day can go a long way (based on Ayabe. 2012)

  Frequent everyday activity prevents visceral fat gain This is the result of a study which investigated the relationship between the frequency of everyday physical activity and visceral adipose tissue mass in 42 Japanese women, aged between 40 to 60 years (Ayabe. 2012). A brief look at the figure on the right will suffice to see that the problem of our society (and the US society probably even more than the European or Japanese) is not necessarily too little exercise, but much more fundamentally no movement at all during our everyday lives. I mean, 2 of the women did not even have 1 bout of 1-min moderate physical activity, 9 did not move for 3 min a day - is it a wonder we are having serious problems, then?
  Tip: Take a WALK! The results of another recently conducted study, which found that 30 min of brisk walking at approximately 60% of maximum heart rate after a meal reduce post-prandial lipidemia in healthy normolipidemic men, only corroborates the importance of daily physical activity (standing for 45min did not make a difference, btw; cf. Miyashita. 2012). While we do have the stress right after launch, we don't have the "exercise" that would historically be associated with the latter - and as of late this is not just the case for white collar workers like me ;-)
• Active vitamin D does what vitamin D3 doesn't do, ameliorate the oxidative damage due to high fat diets. While the few vitamin D3 supplementation trials in rodents and humans were real non-starters, when it came to the purported effects of "everyone's darling vitamin" against diet induced obesity, diabetes, inflammation, etc. a group of Saudi Arabian researchers has just published the second of two papers within the past two months which deal with the effects of active vitamin D, aka calcitriol, on the diet induced damage in muscle and liver tissue (Alkharfy. 2012).

  

  Figure 4 (Zhu. 2012): Vitamin D3 is converted to the active metabolite 1,25(OH)2D3 by sequential 25-hydroxylation and 1a-hydroxylation. If this conversion does not take place (for possible reasons see text) , though, it could be that you don't see any benefits even from exorbitantly high amounts of supplemental vitamin D3

  In the July issue of Molecules, the scientists had already presented data on the preventive effect calcitriol had on the myocyte damage (weak, pre-degenerate mitochondria, loss of connections among myofibrils) they observed in the muscle fibers of mice who had been fed a high fat diet for 12 weeks. Now, roughly a month later, the researchers from the King Saud University in Riyadh, Saudi Arabia, report similar beneficial effects on weight-related systemic inflammation and ultrastructural changes of the liver during a 16-week rodent study. Compared to the non-supplemented mice, the mice on the calcitriol enriched high fat diet had reduced concentrations of TNF-α, CRP and IL-6 (p < 0.05) and a way higher insulin sensitivity (C-peptide and insulin levels of 539.4 ng/ml versus 718.9 ng/ml and 0.77 ng/ml versus 1.7 ng/ml, respectively; p <0.05). Moreover, the potentially toxic calcitriol protected the liver of the mice from the marked accumulation of fat droplets Alkharfy et al. observed in 60-70% of the hepatocytes of the mice that were fed the non-supplemented high fat diet.
  The profound weight loss the animals in the HFD + calcitriol trials experienced in both trials (even the LFD control did gain some weight!), should yet remind you that there is a good reason that you can't buy calcitriol over-the-counter at your local GNC and better don't reach out to whatever other sources you may just have been thinking about!
  That said, it is still remarkable that in a mouse model of prostate and breast cancer, dietary vitamin D3 (cholecalciferol) and thrice weekly injections of calcitriol worked equally well (Swami. 2012), while the cholecalciferol from your average vitamin D supplement sucks, when it comes to the metabolic effects everyone is promising you, you would see if you just bumped your 25-OHD levels to whatever novel heights. At least in the case of the obese rodents, a possible reason could simply be that obesity prevents it's conversion. That this appears to be the case is something we have already discussed in the context of the defect in the enzymatic cascade in obese patients in a previous installment of "On Short Notice". And if it's not obesity that hinders vitamin D from doing its purported job, you still got my hypothetical rants about the exuberant phosphate intake from the average western diet and its negative impact on the conversion of cholecalciferol to calcitriol (see "Hypothesis: Does Vitamin D 'Deficiency' Protect Us From Phosphorus Overload?")

• 

  Figure 5: ECGC may be more potent in the in-vitro essay (left, background; anti-lipase effect rel. to Orlistat), its susceptibility to digestion (bottom, right) renders it yet ineffective as a "fat blocker" (left, foreground; FFA during simulated digestion). Appropr. dosed (1-3 serv./day), coffee and gomchui tea thus appear to be better suited to reduce fat digestion and absorption (Cha. 2012).

  With di-O-caffeoylquinic acid, Gomchui (Ligularia fischeri) Tea easily outperforms coffee and green tea as an inhibitor of fatty acid breakdown in the stomach - what could in fact turn against you on an already fat-deficient (yeah, there is such a thing!) diet, could be a useful tool for the transient phase from diet-induced obesity to natural leanness on a totally revamped diet + exercise regimen, as well as the occasional "binge", you may planning to have if you are already following a healthy whole foods diet.
  Published in the July issue of the Journal of Agriculture and Food Chemistry a recent the study by Cha, Song, Kim and Pan  shows quite conclusively that a tea that's brewed from Lingularia fischeri (gomchui) can decrease the activity of the fat-digesting enzymes in your gut and thus minimize the energy influx from free fatty acids.
  What's also intriguing about this research is that green tea, despite having the highest content of EGCG and thus theoretically the most potent lipase inhibitor of all the three beverages (green tea, coffee and gomchui tea) had - as soon as a certain dosage threshold of 2-3 servings was achieved, the least effect on on lipase activity in the digestion model the scientists used. If your goal is to ameliorate the potential weight gain right after a binge, gomchui or even a strong black coffee would probably be better choices than a cup of green tea.

  

  Figure 6: The effect green tea extracts have on the synthesis (FAS), transport (CPT II) and oxidation (ACO) of fatty acids in the liver, depend on both EGCG and caffeine (Suigiura. 2012)

  In this context, it is also worth mentioning that a related study by Sugiura et al. that has been published in the Journal of Obesity found that the inhibitory effects of EGCG on FAS (fatty acid synthase, i.e. the exact opposite of lipase) expression in the liver, reach statistical significance only in the presence of caffeine (Sugiura . 2012).
  This would render the use of decaffeinated green tea extracts for weight-loss purposes at least less effective than the consumption of real green tea. You could probably still grasp the beneficial downstream effects of the anti-inflammatory effects of EGCG, but would miss out on the "fat burning" and "anti-fat depositioning" effects (esp. in the liver), as those are obviously reliant on the simultaneous presence of caffeine. Needless to tell you that this is exactly the way nature has intended it, right? I guess it's about time to have a cup of good tea now... or maybe coffee - or Gomchui?

That's it already for today, but never mind, there will be more. In the next installmenta of "On Short Notice", my daily news-updates on the SuppVersity Facebook Wall (today with news on the muscle building effects of cortisol + IGF1 and more) and - from now on - every Thursday on Super Human Radio (click here to download the first installment of the thursdaily "Super Human Radio + SuppVersity Joint Research Update"). And aside from that there are of course your daily "regular" SuppVersity News!

References:

• Alkharfy KM, Al-Daghri NM, Ahmed M, Yakout SM. Effects of vitamin d treatment on skeletal muscle histology and ultrastructural changes in a rodent model. Molecules. 2012 Jul 31;17(8):9081-9. 
• Alkharfy KM, Al-Daghri NM, Yakout SM, Ahmed M. Calcitriol Attenuates Weight-Related Systemic Inflammation and Ultrastructural Changes of the Liver in  a Rodent Model. Basic Clin Pharmacol Toxicol. 2012 Aug 21. 
• Ayabe M, Kumahara H, Morimura K, Sakane N, Ishii K, Tanaka H. Accumulation of Short Bouts of Non-Exercise Daily Physical Activity is Associated with Lower Visceral Fat in Japanese Female Adults. Int J Sports Med. 2012 Aug 17.  
• Cha KH, Song DG, Kim SM, Pan CH. Inhibition of Gastrointestinal Lipolysis by Green Tea, Coffee, and Gomchui ( Ligularia fischeri ) Tea Polyphenols during Simulated Digestion. J Agric Food Chem. 2012 Jul 25;60(29):7152-7. 
• Childhood Obesity Action Network. State Obesity Profiles, 2009. National Initiative for Children's Healthcare Quality, Child Policy Research Center, and Child and Adolescent Health Measurement Initiative. Retrieved 06/02/2010 from http://wwww.nschdata.org/content/07obesityreportcards.aspx.
• Gutiérrez-Rosales F, Ríos JJ, Gómez-Rey ML. Main polyphenols in the bitter taste of virgin olive oil. Structural confirmation by on-line high-performance liquid chromatography electrospray ionization mass spectrometry. J Agric Food Chem. 2003 Sep 24;51(20):6021-5.
• Jemai H, Bouaziz M, Fki I, El Feki A, Sayadi S. Hypolipidimic and antioxidant activities of oleuropein and its hydrolysis derivative-rich extracts from Chemlali olive leaves. Chem Biol Interact. 2008 Nov 25;176(2-3):88-98. Epub 2008 Sep 7.
• Lissner L, Lanfer A, Gwozdz W, Olafsdottir S, Eiben G, Moreno LA, Santaliestra-Pasías AM, Kovács E, Barba G, Loit HM, Kourides Y, Pala V, Pohlabeln H, De Henauw S, Buchecker K, Ahrens W, Reisch L. Television habits in relation to overweight, diet and taste preferences in European children: the IDEFICS study. Eur J Epidemiol. 2012 Aug 22.
• Oi-Kano Y, Kawada T,Watanabe T, Koyama F,Watanabe K, Senbongi R, et al. Extra virgin olive oil increases uncoupling protein 1 content in brown adipose tissue and enhances noradrenaline and adrenaline secretion in rats. J Nutr Biochem. 2007;18:685–92.
• Oi-Kano Y, Kawada T, Watanabe T, Koyama F, Watanabe K, Senbongi R, Iwai K. Oleuropein supplementation increases urinary noradrenaline and testicular testosterone levels and decreases plasma corticosterone level in rats fed high-protein diet. J Nutr Biochem. 2012 Aug 15. 
• Omar SH. Oleuropein in olive and its pharmacological effects. Sci Pharm. 2010;78(2):133-54. Epub 2010 Apr 23.
• Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhalder B, Bartsh H. The antioxidant/anticancer potential of phenolic compounds  isolated from olive oil, Europ. J. Cancer. 2000; 36:1235–1247. 
• Sugiura C, Nishimatsu S, Moriyama T, Ozasa S, Kawada T, Sayama K. Catechins and Caffeine Inhibit Fat Accumulation in Mice through the Improvement of Hepatic Lipid Metabolism. J Obes. 2012;2012:520510.
• Zhu J, DeLuca HF. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet? Arch Biochem Biophys. 2012 Jul 1;523(1):30-6

On Short Notice: Ghrelin & GH Boosting Fats for Intermittent Fasting, 4-AD, 5-AA, Testosterone & Co in "Pod", Too Much Vitamin D for Your Prostate, Estrogens in Milk & More

Image 1 (fidged-group.co.uk): Being average may not be sexy, but one thing I did not mention in the summary of what you are going to learn today is that an average amount of body fat (not the new average American though ;-) could hold the key for a longer life - ah, I almost forgot: This is only valid if it comes with an appropriate amount of lean mass, which is still the best predictor of a long and healthy life!

Somehow these On Short Notice posts become increasingly longer... I had to "outsource" a couple of items, to reduce today's installment to a manageable length, but don't worry a couple of them will turn up in the next installment or make it into the regular news in the days to come. For now you will have to settle for valuable and at least in part surprising insights into the broad range of effects different types and loads of dietary fat can have on your appetite, metabolism and your, or rather your bacterial subtenants' methane production. You will also learn what TAC means and why you want more than 1,080 units of it in every 100g of whatever you are stuffing down your pie-hole. You will be surprised to hear that SuppVersity student FatFree instinctively chose the low estrogen variety of dairy, when he "downed 1l of raw goat's milk" from his local farmer earlier today (see respective comment) and you will attend another lesson of the "what's good for your obese neighbor, is not necessarily good for you" class. All that will be topped of with some testosterone laden, WADA prohibited "pod", too much vitamin D for your prostate to handle and a glass of bone-conserving wine for the habitual drinkers among the ladies ;-)

Fat Interactions - MUFA, PUFA, SUFA and How They Influence Your Metabolism

The idea that "not all fats" are created equal is meanwhile broadly accepted. What is still a matter of constant debate, though, is which of the three main classes, i.e. saturated, mono- and polyunsaturated fatty acids exert beneficial and which of them detrimental effects on our health. A recently published on the differential effects of butter (saturated fat), olive oil (mono-unsaturated; oleic acid + a relative high amount of omega-6), fish oil (polyunsaturated; high omega-3) and soybean oil (polyunsaturated; mainly omega-6 + some omega 3) on the expression of the purported "hunger hormone" ghrelin (note: acetylghrelin, which was measured in this study, is the "active" variety of ghrelin) may yet help to get a better grasp of what exactly we should be looking for (Saidpour. 2012), when it comes to the downstream metabolic effects of high amounts of certain fatty acids - and no, it is not for maximal ghrelin suppression.

Figure 1: Food intake (in g, left), body weight (relative to control group on regular diet, middle) and acetylghrelin levels in the fasting and fed state during the 8-week experimental period (data based on Saidpour. 2012)

As the data data in figure 1 shows, the 5-week old male Wistar rats who had been randomly assigned to either standard rodent chow or calorically identical (3.98kcal/g of food) high fat diets who were fed ad libitum every other day only to maximize the ghrelin response) for 8 weeks did not, as common sense would suggest, eat the least and gain the least on the saturated fat (butter) diet with its long lasting satiety effect (as evidenced by the lowest fasting ghrelin levels).

In fact, the exact opposite was the case: The acute satiety effect of the fish oil and olive oil diets (as evidenced by the plummeting acetylghrelin levels in the fed state) turned out to be the main determinant of the amount of food the rodents, who were effectively intermittently fasted (though with a pretty long fasting window of 24h), consumed.  And while the low ghrelin levels in the fed state reduced the food intake, the fasting induced rise of acetylghrelin to 23% higher levels than in the butter fed animals has probably given them the metabolic advantage of elevated growth hormone levels. At least this is what we must expect based on the ability of ghrelin to directly bind to the GHS receptor and induce the release of the fat annihilating 191-amino acid, single-chain polypeptide from the lateral wings of the anterior pituitary gland (Kojima. 1999).

Bottom line: While this is certainly only another small piece to the oftentimes puzzling effects of fatty acids (check the "On Very Short Notice" items in this installment for more "puzzling" effects ;-), it does not only provide another mechanism by which the original "Mediterranean diet", which is rich in both fish and olive oil and by no means as fat free as its latest mainstream interpretation would suggest, could in fact provide a metabolic edge. And though the "intermittent fasting" feeding pattern may reduce the significance of the results for the "average" inhabitant of the Western hemisphere, who can hardly go 2h without a Snickers bar or at least a sugar-laden coffee, it does suggest that all the "lean gainers" and "intermittent fasters" out there could derive great benefits from a huge piece of salmon and couple of tablespoons of high MUFA olive, macadamia or artichoke oil in their "feeding windows".

A Diet High in Dietary Antioxidant Keeps you Lean & Healthy

Image 2: Clover is among the most potent antioxidant foods.

You know that I am very critical when it comes to the supply of exogenous antioxidants (cf. "Multivitamins, a question of Faith?!"; more on multivatmins), but would never even remotely consider limiting the supply of whole foods that are rich in antioxidants. I was thus not very surprised, when I read that the consumption of high amounts of dietary antioxidants was associated with statistically significant lower body weight and abdominal fat gain in a 3-year longitudinal (this is where scientists analyze data from the same persons on different time-points) study from the University of Medical Sciences in Teheran (Bahadoran. 2012).

Foods	TAC
Cloves (see image), Cinnamon, Oregano, Tumeric, Acai (all dried or grounded)	300,000 -100,000
Cacao, Parsley, Basil, Currry, Sage, Peppercorns, Mustard, Ginger, Marjoram	100,000 -25,000
Rice bran, Chili, Pecans, Paprika, Choke berries, Elderberries, Kidney Beans (dried), Oregano, Walnuts	25,000 -10,000
Hazelnuts, Cranberries, Artichoke hearts, Blueberries, Prunes, Pistachios, Blackcurrant, Artichokes, Plums, Blueberries (cult.) Lemon balm (fresh) Blackberries, Garlic, Coriander,	10,000 -5,000
Raspberries, Basil (fresh), Almonds, Apples, Dates, Strawberries, Figs, Peanuts, Raisins, Cherries, Asparagus, Spinach	5,000 -2,500
Cornflakes, Red Cabbage, Gooseberries, Cashews Avocado, Pears, Peaches, Oranges, Oats, Macadamia, Tangerines, Broccoli, Potatoes, Grapefruit, Red grapes	2,500 -1,500
Carrots, Olive oil, Green grapes, Mango, Lettuce, Radish Eggplant, Kiwi, Banana, Red pepper, Pineapple, Artichoke, Nectarines, Pine nuts, Cauliflower, celery	1,250 -500
Leeks, Lettuce, Baby carrots, Tomatoes, White wine, cantaloupe, Honeydew, Watermelon, Cucumber	500 -100

In particular, Zarah Bahadoran and her colleagues found that the consumption of foods with an average total antioxidant capacity equal to 1,080µmol TAC essay units per 100g - something your would get from oats + blueberries or a handful of pecans and an apple - was associated with a -38 % decrease in the risk of central obesity (note: The TAC essay is an experimental measure of the total antioxidant capacity of food and is independent of whether it's phenols, vitamins, thiols or whatever that contribute to the antioxidant effects of a food; the clear disadvantage of this method is that it does not really tell you what exactly the compounds will do outside of a petri dish, but, but this is the topic for another blogpost ;-)

And while some of the confounding factors have been eliminated from the above hazard risk calculations, it is still worth to take note of the fact that...

• people with the highest antioxidant intake consumed food with the lowest energy density (so they cannot be eating nuts and chocolate only ;-)
• women consumed significantly more antioxidants than men, with +10% more women in Q3 (959-1080µmolTE/100g) and +15% more women in the critical Q4 (>1,080µmol/kg) quartiles
• the more leisure time the subjects had, or I should say allowed themselves, the higher was their antioxidant intake
• high antioxidant consumers were also dairy lovers with 81% more dairy consumption in the highest quartile, exactly those people, thus, who consumed the >1,082 µmolTE/100mg diets
• needless to say that people who are reckless enough to smoke also consumed the least antioxidants

Aside from these significant differences, the non-existence of other differences people often take for granted, such as the notion that education and job activity, or different macronutrient compositions would have an impact on the total amount of antioxidants you consume, is certainly worth mentioning.

  On Very Short Notice

• 

  Figure 2: "Pod" contains a hell lot of steroids. Unfortunately, most of them will be dumped by right into the urine specimen for the WADA agents (data based on Thevis. 2012)

  "Pod" doping could get you banned, but probably won't increase your performance - While I cannot tell you what the swimmers at the Olympics have been taking to break world record after world record (some even in consecutive races on the same day), I can tell you that it were not the reddish-brown musk grains from the dried secretion from the preputial follicles of the male musk deer , which are located in the "pod", a small sac in close proximity to the preputial orifice (see figure XYZ, upper right), because none of these athletes would have passed the WADA doping controls had he or she taken a couple of grams of those steroid-containing staples of Traditional Chinese Medicine.
  Now, despite the fact that we do see "classics" such as 4-AD, Androsterone, Epiandrosterone, DHEA and even minuscule amounts of the "Big T" (1-6µg/g with the highest level in the pod from the zoo animals from Leipzig, Germany - read more about testosterone's ability to build muscle in the "Intermittent Thoughts on Building Muscle") testosterone , the total amount of those compounds which could actually induce noticeable performance increases may be high enough to show up during doping controls as the five cases during the last FIFA Women World Cup show(cf. Thevis. 2012), it does not appear reasonable to assume that the rumored performance enhancing effects of musk (pod) extracts would stand the test in a placebo controlled supplementation trial.

• 

  Figure 3: When administered at a HED of ~750mg/day sodium salicates reduce the glucose (left axis) and insulin (right axis) levels in response to a standardized intraperitoneal glucose injection in obese mice, they do the opposite in lean mice (based on Nixon. 2012).

  Salicates block cortisol expression in fat cells and increase insulin sensitivity in obese mice, but... as we have seen for alpha lipoic acid (see "ALA? You are Better of Without the Purported Nutrient Repartitioner") and tons of other "wonder-supplements", things that are good for your obese neighbor will rarely work out for lean folks like, yourself; and thus it should not come as a surprise that the blockade of adipose tissue 11-beta-HSD, the enzyme that converts cortisone, the inactive form of cortisol into it's active twin, exerts no, if not the exact opposite effect (see figure 3; adapted from Nixon. 2012).
  So, if you are lean and want to stay lean, leave the aspirin, the 7-ketos and other overpriced 11-beta-HSD inhibitors or "cortisol blockers" to those who need them - inflamed, overweight (pre-)diabetics.
• Purportedly anti-carcinogenic high vitamin D levels increase risk of prostate cancer - Swedish scientists found a statistically significant trend towards an increased risk of developing prostate cancer with rising vitamin D levels. In the 7th and 8th decile which corresponds to plasma vitamin D levels of 91-97 nmol/L the calculated risk of developing prostate cancer was 67% higher than in the lowest decile (Brändstedt. 2012). Other than previous studies which reported associations between high calcium intake and prostate cancer risk, Brändstedt et al. observed an association between high serum calcium levels and prostate cancer levels only among men aged 55-65 who had a BMI < 25. It is thus very unlikely that the underlying reason of the pro-carcinogenic effects was an increase in calcium absorption... hmm, I don't have to remind you of (a) the antagonism between vitamin D and vitamin A and (b) last weeks news on the anti-carcinogenic effects of the latter, do I?

• 

  Image 3: Although the scientists controlled the compliance by measuring the serum concentration of fatty acids instead of using unreliable food logs, there are still  a lot of uncontrolled confounding variable, here. Hower, the same can be said of those studies on which the concept of the pro-inflammatory omega-6s is based. Anyway, I will still eat butter, not margarine and if olive oil is one of staple sources of dietary fat, you will be getting plenty of omega-6 from this purported GH booster (see previous new item)

  High omega-6 diet reduces insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides - Helena Bjermo and her colleagues from the Uppsala University in Sweden report that feeding 67 abdominally obese patients (15% were diabetic) either a butter-based high saturated fat diet or a diet that was particularly rich in linoleic acid (omega-6 mainly from sunflower oil; 15% of the total energy intake) for 10 weeks had very differnt effects on the hepatic fat content an other highly relevant markers of metabolic health. Despite the fact that both diets were isocaloric, the butter-based high saturated fat diet increased the hepatic fat content of the study participants (measured by MRS) by 10% while the subjects in the high PUFA group were able to reduce the fat content of their livers by -35%. Similarly, the basal insulin level, triglycerides, as well as total and LDL cholesterol increased in the butter eaters and decrease or remained the same in the 15% linoleic acid group.
  The results are honestly not what I had expected, but in essence only further evidence there is still a lot to learn about the shades of grey that exist between the dichotomous black and white that is still so characteristic of the way we think about fats.
• Goat's milk is the better choice for people concerned with limiting their intake of exogenous estrogens - According to analyses that were conducted at the Laboratory of Proteomics and Analytical Technologies in Frederick (Farlow. 2012), cow's milk contains significantly more estrogens (estrone and 17beta-estradiol) than goat's milk and that irrespective of whether it was organically produced or not. Bad news for the reproductive health of the North Americans and Europeans, where the consumption of cow's milk exceed that of goats milk by several magnitudes and good news for the fertility of the rest of the world, where goat's milk still is the "milk of choice".

• 

  Image 4: Looks like this was not the only potential side effect of methane producing bacteria in your gut.

  High fat diets increase the ratio of methane producing to other bacteria and thus increase obesity risk - Most of you will probably remember the finding that mice without gut microbiome are more or less resistant to dietary induced obesity. A recent study does now suggest that (as it was to be expected) not all bacteria are created evil.. ah, pardon... equal ;-) In the lab mice of Ruchi Mathur and his colleagues, the tendency to develop obesity correlated with the amount of gastrointestinal (GI) methanogens, including Methanobrevibacter smithii, and was independent of the presence of other bacteria (Mathur. 2012).
  With the pro-methanogenic (=allows those little bastards to grow) effects of high fat diets Mathur et al. may in fact have found another potential co-founder in the development of the metabolic syndrome. Interestingly enough Methanobrevibacter smithii is also the predominant methanogen in patients with constipation-dominant IBS and methane breath (Kim. 2012) - so if that is you, this could be one of the few cases where the use of a broadband antibiotic could save you from a lot of ailments, because you would thus not have to care about contradictory results from Million et al., as well as dozens of other studies, each of which identifies another type of bacteria as 'the root cause' of the obesity epidemic - in Million's case the name of the scapegoat is Lactobacillus reuteri, by the way (Million. 2012).
• Mediocrity guarantees a long life - At least when it comes to body fatness being too lean and being too fat are equally detrimental to the life expectancy of male 65+ agers (Toss. 2012). If you are women, though, the results Fredrik Toss and his colleagues published in the latest issue of Age and Ageing suggest that being on the chubbier side of things can actually be life-saving, as long as you carry the fat in the gynoid and not the abdominal area. Most importantly, however, lean mass, or as my buddy Carl Lanore calls it, "metabolic currency" is yet still the most significant predictor of survival in older subjects - in other words: Don't even think of emulating the skinny fat celebrities with their starvation diets and endless cardio sessions if you intend to live your grand- and grand-grand-children, better check out yesterday's news on the "Iranian HIIT Solution for Improved Insulin and Leptin Sensitivity".

• 

  Image 5: If you are concerned about bone health, menopause is not the best time to stop drinking... unless you start weight lifting, of course ;-)

  Don't stop drinking alcohol in menopause! At least if you don't want to increase bone-resorption, i.e. the leeching of calcium from your bones. This is the surprising result of a recently published study by Jill A. Marrone and colleagues, who had  investigated the effects of total abstinence from alcohol in 40 healthy postmenopausal women (mean ± SE age, 56.3 ± 0.5 y) who consumed the alcohol equivalent of ~1 glass of wine per day (Marrone. 2012). Interestingly, the bone formation marker osteocalcin and the resorption marker C-terminal telopeptide (CTx) returned to their normal values, once the women resumed their former drinking habits.
  In view of the fact that there was also a significant correlation between baseline bone-density, as measured dual-energy x-ray absorptiometry, and the extent of mild to moderate alcohol consumption, these results raise the question whether "bone health" would be another factor to add to the list of the "minimalist approach" to alcohol consumption.

References:

• Bjermo H, Iggman D, Kullberg J, Dahlman I, Johansson L, Persson L, Berglund J, Pulkki K, Basu S, Uusitupa M, Rudling M, Arner P, Cederholm T, Ahlström H, Risérus U. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr. 2012 May;95(5):1003-12. 
• Brändstedt J, Almquist M, Manjer J, Malm J. Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case-control study. Cancer Causes Control. 2012 Aug;23(8):1377-85.
• Farlow DW, Xu X, Veenstra TD. Comparison of estrone and 17β-estradiol levels in commercial goat and cow milk. J Dairy Sci. 2012 Apr;95(4):1699-708.
• Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., Kangawa, K. Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature. 1999; 402, 656-660.
• Mathur R, Kim G, Morales W, Sung J, Rooks E, Pokkunuri V, Weitsman S, Barlow GM, Chang C, Pimentel M. Intestinal Methanobrevibacter smithii but Not Total Bacteria Is Related to Diet-Induced Weight Gain in Rats. Obesity (Silver Spring). 2012 Jun 7. 
• Marrone JA, Maddalozzo GF, Branscum AJ, Hardin K, Cialdella-Kam L, Philbrick KA, Breggia AC, Rosen CJ, Turner RT, Iwaniec UT. Moderate alcohol intake lowers biochemical markers of bone turnover in postmenopausal women. Menopause. 2012 Jul 9.
• Million M, Maraninchi M, Henry M, Armougom F, Richet H, Carrieri P, Valero R, Raccah D, Vialettes B, Raoult D. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes (Lond). 2012 Jun;36(6):817-25.
• Nixon M, Wake DJ, Livingstone DE, Stimson RH, Esteves CL, Seckl JR, Chapman KE, Andrew R, Walker BR. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization. Diabetes. 2012 Apr;61(4):790-6.
• Saidpour A, Kimiagar M, Zahediasl S, Ghasemi A, Vafa M, Abadi A, Daneshpour M, Zarkesh M. The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats. Gene. 2012 Jul 25.
• Thevis M, Schänzer W, Geyer H, Thieme D, Grosse J, Rautenberg C, Flenker U, Beuck S, Thomas A, Holland R, Dvorak J. Traditional Chinese medicine and sports drug testing: identification of natural steroid administration in doping control urine samples resulting from musk (pod) extracts. Br J Sports Med. 2012 May 6.
• Toss F, Wiklund P, Nordström P, Nordström A. Body composition and mortality risk in later life. Age Ageing. 2012 Jul 20.