No Advantage of Bolus Ingestion of EAAs in Young Men!? Cereal Bread Not Better for Weight Control. Saturated Fat & the Heart. Plus: Serine for Your Weekend Alcohol Binge!

The "muscle full effect" indicates you don't have to consume 4 scoops at once.

With the publication of the latest issue of The Journal of Nutrition came a handful of interesting scientific papers I will briefly introduce in today's SuppVersity Nutrition Science Update.

The corresponding studies deal with the link of saturated fat to heart disease (Puaschitz. 2014), the effects of proteinogenic amino acid serine (one of the non-essential amino acids) on homocysteine metabolism in a rodent model of alcoholic fatty liver disease (Sim. 2014).

And when we're through with those, we will take a closer look at the effects of cereal enriched breads on the appetite ratings and postprandial glucose, insulin, and gastrointestinal hormone responses related to hunger and satiety in healthy men and women (Gonzalez-Anton. 2014), and the "muscle full effect", or rather limits to maximal protein synthesis in man (Mitchell. 2014).

Read more short news here at the SuppVersity

Obesity Research Upd. Nov. '14

Exercise Res. Upd. Nov '12(1)

Exercise Res. Upd. Nov '12(2)

Nutrition Res. Update Nov. '14

Weight Loss Tricks & More

Reductive Stress, Iron & the Military

• Saturated fat and your heart - Right from the Haukeland University Hospital in Norway comes a new study that investigated the associations between self-reported dietary SFA intake and risk of subsequent coronary events and mortality in patients with coronary artery disease (CAD).
  
  The study included patients who participated in the Western Norway B-Vitamin Intervention Trial and completed a 169-item semiquantitative food-frequency questionnaire after coronary angiography - 2412 patients, total, 81% men, 19% women with a mean age of 61.7 y.
  After a median follow-up of 4.8 y, a total of 292 (12%) patients experienced at least one major coronary event during follow-up.  And while a gigh intake of SFAs was associated with a number of risk factors at baseline, "there were no significant associations between SFA intake and risk of coronary events [age- and sex-adjusted HR (95% CI) was 0.85 (0.61, 1.18) for the upper vs. lower SFA quartile] or any secondary endpoint. Estimates were not appreciably changed after multivariate adjustments" (Puaschitz. 2014).
  

  

  Figure 1: Hazard ratios according to % saturated fat intake of total energy intake compared to minimal saturated fat intake (HR = 100%) in 2412 subjects (Puaschitz. 2014).

  In other words, if you ask researchers from Northern Europe, their answer to the question, whether our high intake of saturated fats is the reason we are dying prematurely from heart disease is "no". This stand in line with a recent review of the current evidence by O'Keffee et al. who point highlight that the different results (which often depend on the country, where the studies are conducted) may be attributable to the fact that "not all SFA are created equal and the food sources of SFA". Accordingly the researchers from the King's College in London, the Luke’s/Roosevelt Hospital, the New York Nutrition Obesity Research Centre and the Columbia University in New York recommend that "individual characteristics of the SFA, such as chain length, should be considered in dietary recommendations" (O’Keeffe. 2014)... and I would like to add: In every future study, as well.
  
  I mean, this and the foods from which the subjects in the study at hand got the majority of their saturated fat intake may well be the reason that there was a statistically significant correlation between high fat intakes and the occurernce of coronary artery disease (remember: all participants had CAD, already) in the cohort Western Norway B-Vitamin Intervention Trial.
• L-Serine as super-supplement for binge drinkers? At least in rodents the provision of 200mg/kg body weight (for humans this would be ~1.2-1.5g/day) serine in the diet led to an attenuation of alcohol-induced increases in serum homocysteine and hepatic triglyceride (TG) concentrations (>5-fold in the control mice) by 60.0% and 47.5%, respectively.
  

  

  Figure 2: Liver triglyceride levels, serum ALT and serum homocysteine levels in control mice (C) and "binge drinking mice" (EV) with and without 20mg/kg (ES20) and 200mg/kg (ES200) serine in their diets (Sim. 2014)

  Moreover, in the chronic ethanol study, l-serine also decreased hepatic neutral lipid accumulation by 63.3% compared with the ethanol group and ramped up the glutathione and S-adenosylmethionine content of the liver by 94.0% and 30.6%, respectively.
  
  If we assume that serine is only half as powerful, when it is given to humans, I would recommend you drink your Vodka Red Bull with serine in the future ;-)
• Super-satiating cereal enriched breads - I guess "super-satuating" is an exaggeration, but there is no doubt that the addition of variety of cereal flours (wheat, oat, and spelt) and 22% dried fruits (figs, apricots, raisins, and prunes) to regular bread lead to a significant improvement of appetite control by reducing hunger and enhancing satiety in 30 healthy adults (17 men and 13 women) aged 19–32 y with body mass index of 19.2–28.5 who participated in an experiment that was conducted at the University of Granada in Spain (Gonzalez-Anton. 2014).
  

  

  Figure 3: The hormonal changes would indicate increased satiety, the subjects reported increased satiety, but their 4h energy intake was identical in both condition (Gonzalez-Anton. 2014)

  Whether the decrease in prospective consumption and increased satiety is enough to have long-term benefits on weight control is yet questionable, because the subsequent ad libitum energy intake in a 4 h period after the ingestion of the "enriched" bread did not differ from that in the control condition, even though the postprandial blood glucose, insulin, ghrelin, were lower and the pancreatic polypeptide AUC (an indicator of satiety) was higher than with the control bread.
  
  Speaking of insulin: In view of the fact that the latter actually is a satiety hormone and its release is closely related to glucagon-like peptide (GLP) 1 and gastric inhibitory polypeptide (GIP) where the AUC (areas under the curve) were lowered as well, it's eventually maybe not too surprising that the "enriched" bread was not better than the regular one.
• Muscle full? What's limiting protein Synthesis? Scientists from the Clinical, Metabolic, and Molecular Physiology, MRC–Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research at the University of Nottingham and the Royal Derby Hospital in the United Kingdom recently determined the effect of Bolus (=all the aminos at once) vs. Spread EAA feeding in young men, hypothesizing that muscle-full is regulated by a dose-, not delivery profile–, dependent mechanism; and what they found was surprising for us - not for the researchers, though:

  

  Figure 4: Even though the study was conducted in young men, the overall dosage of 15g may potentially have had an effect on the outcome. On the other hand: If you "overdose" it would actually be more likely for spread protein ingestion to have superior effects. Against that background the "low" dose of "only" 15g of pure EAAs is not an argument that would falsify the results of the study at hand (Mitchell. 2014)

  "Despite distinct plasma and muscle profiles, Bolus feeding provided no anabolic advantage over Spread feeding (or vice versa); these findings are in keeping with our hypothesis of there being an intrinsic muscle-full state in young men at rest.
  
  Bolus feeding led to rapid aminoacidemia with a brisk upstroke and high peak plasma EAA and leucine concentrations. Spread feeding, by comparison, resulted in lower, later peak concentrations. Despite this, identical MPS responses were observed, even with the same latency (of ~90 min) and amplitude.
  
  Furthermore, with both feeding strategies, basal MPS was observed 180 min after consumption of either Bolus or the initial Spread doses. This preceded the peak Spread plasma EAAs, in keeping with the onset of a muscle-full state.

  As the scientists point out, their results do thus "suggest that, in healthy young men, it is dose dependent mechanisms that regulate the size of the anabolic response to feeding and that this response" and that this dose-dependent anabolic response "is not perturbed by later arriving, lower-amplitude aminoacidemia." The researchers also highlight hat it would seem "vital to have such a mechanism in place"; because of the "stability of muscle mass from year to year in healthy younger populations" (Mitchell. 2014). Eventually, the differences may well be explained by the existence of three distinct phases in the postprandial period, the scientists argue:
  

  

  Figure 5: Absolute changes in FSR from fasted (2120 to 0 min) to fed (0 to 240 min) (A), actual FSRs (B) and plasma EAA and insulin concentrations, phospho- 4EBP1 Thr65/70 and muscle protein synthetic rates, normalized to their own data spans shown on the same axis (C and D) in young men after consumption of 15 g of mixed-EAA meals by Bolus or Spread treatment. The black arrows represent ingestion of 15 g EAAs once, and the gray arrows represent ingestion of 3.75 g EAAs 4 times (Mitchell. 2014)

  "After the onset of essential aminoacidemia, a latent period exists when a significant negative arteriovenous EAA balance is detectable (Mitchell. 2013) but incorporation of EAAs into newly synthesized myofibrillar proteins is not. The existence of a similar latent period in response to Bolus and Spread EAA ingestion suggests that providing time for adequate intracellular EAA accumulation, even with rapid aminoacidemia with Bolus, is crucial before MPS can be ‘‘switched on.’’ After this latent period, a transient stimulation in MPS, lasting ;90 min (Bohé. 2001), occurs before the onset of the muscle-full state restores basal MPS despite sustained, near-peak postprandial EAA availability" (Mitchell. 2014).

  Put simply, it takes long enough for the muscle protein synthesis to gain full speed to incorporate all the amino acids the healthy subjects received in 4x45min boluses.
  
  Practically speaking this does not necessarily mean that you should give up your previous protein feeding strategies. With intact proteins, of which you know that they are more than the sum of their EAA parts (see "Whey Beyond Brawn"), studies by Moore et al. (2012 | learn more) and Burke et al. (2012 | learn more) yielded different results... albeit with less frequent biopsies that were taken across the postprandial period and thus a lower temporal resolution that does not exclude that said studies simply overlooked the dose-dependency of the muscle-full effect Mitchell et al. demonstrate in the study at hand.

10+ Things You Probably Didn't Know Whey Protein | more

So what are the take home messages from today's research update? I guess the one you will be most interested in, is the related to the Mitchell study which indicates that protein timing and / or the importance of bolus ingestions may previously have been overrated - at least in the short run. We should not forget, after all, that this is a result that would stand in line with Alan Aragon's & Brad Schoenfeld's recent review (Aragon. 2014  on nutrient timing which found a significant effect for the amount of protein people consume, but no evidence of the purported importance of protein timing.

This is yet not the only myth that is tumbling. The idea of heart disease triggering saturated fats and the notion that you could make bread a superfood by adding cereals and dried fruits did not get away unscathed either. With the impressive effects of serine in the rodent study by Sim et al. (2014), we do have another myth to bother with - one of which I would like to remind you that it has to remain a myth until the results have been confirmed in human beings | Comment on Facebook!

References:

• Aragon, Alan Albert, and Brad Jon Schoenfeld. "Nutrient timing revisited: is there a post-exercise anabolic window." J Int Soc Sports Nutr 10.1 (2013): 5.
• Bohé, Julien, et al. "Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids." The Journal of physiology 532.2 (2001): 575-579.
• Burke LM, Hawley JA, Ross ML, Moore DR, Phillips SM, Slater GR, Stellingwerff T, Tipton KD, Garnham AP, Coffey VG. Preexercise aminoacidemia and muscle protein synthesis after resistance exercise. Med Sci Sports Exerc. 2012 Oct;44(10):1968-77.
• O’Keeffe, Majella, and Marie-Pierre St-Onge. "Saturated Fat and Cardiovascular Disease: A Review of Current Evidence." Current Cardiovascular Risk Reports 7.2 (2013): 154-162. 
• Mitchell, William Kyle, et al. "Development of a new Sonovue™ contrast‐enhanced ultrasound approach reveals temporal and age‐related features of muscle microvascular responses to feeding." Physiological reports 1.5 (2013). 
• Mitchell, William Kyle et al. "A Dose- rather than Delivery Profile–Dependent Mechanism Regulates the ‘‘Muscle-Full’’ Effect in Response to Oral Essential Amino Acid Intake in Young Men."J. Nutr. February 1, 2015
• Moore DR, Areta J, Coffey VG, Stellingwerff T, Phillips SM, Burke LM, Cléroux M, Godin JP, Hawley JA. Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males. Nutr Metab (Lond). 2012 Oct 16;9(1):91.
• Puaschitz et al. "Dietary Intake of Saturated Fat Is Not Associated with Risk of Coronary Events or Mortality in Patients with Established Coronary Artery Disease." J. Nutr. February 1, 2015 jn.114.203505
• Sim, et al. "l-Serine Supplementation Attenuates Alcoholic Fatty Liver by Enhancing Homocysteine Metabolism in Mice and Rats." J. Nutr. February 1, 2015 jn.114.199711.

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.

Which Micro- & Macronutrients Intakes Are Associated With High HDL Levels? Study Shows Magnesium & Folate Are, High Carbohydrate & Total Animal Fat Intakes Are Not!

The advantage of HDL is its stability that reduces the risk of plaque build-up in the intestinal wall, which is clogged by the remnants of oxidized LDL and causes heart disease & co.

First things first: We are not talking about "hard experimental evidence" as you could generate it in a randomized controlled trial in a metabolic ward. The data I am reporting today is from a cohort with 1,566 participants with extensive lipid phenotype data completed the Harvard Standardized Food Frequency Questionnaire to determine their daily micronutrient intake over the past year - an epidemiological study that used stepwise linear regression was used to separately evaluate the effects of dietary covariates on adjusted levels of HDL-C, HDL-2, HDL-3, and apoA1.

Interestingly, this is the first study with a quality data-set that determined the association between specific dietary micronutrients with HDL-C, HDL-2, HDL-3, and apoA1, and how these dietary associations differ across the various measures of HDL - not just one.

Learn more about HDL, cholesterol, heart health & co at the SuppVersity

Prohormones mess with your cholesterol.

Every other day fasting for your lipids

Dairy Protein Satiety Shoot-Out: Casein vs. Whey

Fish oil & oleic acid counter their ben. effects

Eggs increase cholesterol reverse transport

Does roasted coffee increase bad LDL?

To identify the HDL-promoters in the diet, the scientists use demographic and clinical variables in the base model. What they found was that numerous dietary intakes increased total HDL-C variance.
The results of their stepwise linear regression model in Table 1 indicate - probably for some people much surprisingly - that all alcohol intake levels were positively associated with HDL-C.

"In addition, magnesium, folate, and the saturated fat, myristic acid (14:0), were all positively and independently associated with HDL-C. Carbohydrate intake, iron, and % of fat derived from animal sources were each negatively additive for HDL-C." (Kim. 2014)

Similar effects from dietary intakes were observed for HDL-2, of which we know that it is decreased in women with rheumatoid arthritis (Arts. 2012) and individuals with other inflammatory diseases (including metabolic syndrom) and associated with a slightly higher reduction in acute myocardial infarction risk than "regular" HDL in several studies (Salonen. Salonen. 1991; Stampfer. 1991; Buring. 1992; Gaziano. 1993) for all alcohol intakes, magnesium, folate, and myristic acid (14:0), eicosapentaenoic acid (20:5, a ω-3 EPA), all of which were positively and independently associated with HDL-2 levels.

Table 1:  Best-fit model from stepwise linear regression predicting HDL-C levels using dietary intake data (Kim. 2014)

The opposite was the case for arachidonic acid (20:4, an ω-6 ARA), carbohydrate and iron intakes, which were both negatively associated with HDL-2 (see Table 1).

Don't forget to put things into perspective!

And just to make sure, I don't get angry emails from bulletproof coffee drinkers: Your coffee is fine, the content of the only "good" saturated fat, i.e. myristic acid, happens to be especially high coconut oil (41%; Sodamade. 2013) and relatively high in butter (12% independent of whether it's grass-fed or not; Couvreur. 2006) - surprised? Not really, I guess. As a SuppVersity reader you are by now aware that the bad reputation coconut oil and butter have for being mostly saturated fats is no longer supported by contemporary scientific evidence (Dias. 2014).

And with respect to the total animal fat intake - for the average Westerner that's a good measure of how much processed meat he / she eats, so I would not overrate the small negative association (1/80 of the one of having a ton of carbohydrates in your diet!) the scientists found in the study at hand.

Eggs are unquestionably and exception from the "animal fat" is bad for HDL rule | learn more.

Bottom line: With the exception of folate, which has previously not been reliably associated with increases in HDL, let alone speficic HDL subfraction, the improvements with alcohol, magnesium and EPA are not exactly news. The same is true for the decreases in response to increased intakes of (all) animal fat, arachidonic acid, carbohydrates and iron.

In the end, the study confirms what we already know: The way you eat (and train; see Leon. 2001) can directly affect the level of the heart-healthy HDL fractions in your blood.

One thing you should keep in mind, though, is that it's the ln = logarithmus of these macronutrients and micronutrients that's associated with increased / decreased HDL and its subfractions. This means that small changes are not really important. Things that would count are eating low carb vs. extreme high carb or eating no folate containing foods vs. a significant amount of these.

References:

• Arts, Elke, et al. "High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study." Arthritis Res Ther 14.3 (2012): R116.
• Buring, J. E., et al. "Decreased HDL2 and HDL3 cholesterol, Apo AI and Apo A-II, and increased risk of myocardial infarction." Circulation 85.1 (1992): 22-29.
• Couvreur, S., et al. "The linear relationship between the proportion of fresh grass in the cow diet, milk fatty acid composition, and butter properties." Journal of dairy science 89.6 (2006): 1956-1969.
• Dias, C. B., et al. "Saturated fat consumption may not be the main cause of increased blood lipid levels." Medical hypotheses 82.2 (2014): 187-195.
• Gaziano, J. Michael, et al. "Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction." New England Journal of Medicine 329.25 (1993): 1829-1834. 
• Kim et al. "Effects of dietary components on high-density lipoprotein measures in a cohort of 1,566 participants." Nutrition & Metabolism 2014, 11:44.
• Leon, ARTHUR S., and OTTO A. Sanchez. "Response of blood lipids to exercise training alone or combined with dietary intervention." Medicine and science in sports and exercise 33.6 Suppl (2001): S502-15.
• Salonen, Jukka T., et al. "HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men." Circulation 84.1 (1991): 129-139. 
• Sodamade, A¹, and O. S. Bolaji. "Fatty acids composition of three different vegetable oils (soybean oil, groundnut oil and coconut oil) by high-performance liquid chromatography." Chemistry and Materials Research 3.7 (2013): 26-29.
• Stampfer, Meir J., et al. "A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction." New England Journal of Medicine 325.6 (1991): 373-381.

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.

Saturated Fat Kills Gut Bacteria & Modifies Genes in the Distal Small Intestine - Another Reason Why We Get Fat? Plus: Bacteria, Fiber, SCFA, GLP-1 & PYY Revisited

Image 1: Bacteria, there are >100 trillion of them right inside of your digestive track, you can hardly know them all and scientists do neither - the only thing we are beginning to understand, though, is that it may be a good idea to get them to know at least somewhat better ;-)

I guess some of you have already noticed that I was (and probably am now, again) somewhat behind, as far as answering your questions, comments an wise remarks are concerned. Actually it is still more of a coincidence that today's SuppVersity news, which, as you see is not an Adelfo Cerame post (don't forget to keep the fingers crossed for him! This is his weekend!), could actually be interpreted as my somewhat lengthy response to a comment from Vincente on the effects of GLP-1 on chocolate preference in rats and an interesting hypothesis of his, on how this could all relate to my previous post on the fat burning effects of GLP-1 ("Eat More, Burn More and Lose Fat Like on Crack with GLP-1!?"). What, that was Vincente's reasoning, what, if those obese individuals had just messed up their gut bacteria an would lack those beneficial bacteria, which convert the fiber and resistant starch that makes it through your small intestine, right down into your long one to short chain fatty acids?

Does obesity come from within?

I guess by now some of you may already be asking themselves, where all that relates to GLP-1 and eating more, burning more and losing fat like on crack. Well, the missing link if you will is actually not a link, but rather a receptor - the free fatty acid receptor, FFR, which "sniffs" the presence of the short chain fatty acids and triggers the release of GLP-1 and PYY. Those two incretin hormones, of which researchers have found within the past 10 years or so that they are way more than mere "satiety signals. Several research studies in rodents have shown that the anti-obesogenic effects of GLP-1 and PYY are if at all, only partly mediated by reductions in food intake, yet mostly via complex downstream effects on total energy expenditure, glucose and fatty acid oxidation.

Contrary to exogenously administered GLP-1, which is actually being used in the treatment of diabetes an the metabolic syndrome, the in-vivo data from rodent studies, which suggests that high fiber diets protects those little critters from diet induced obesity (Aziz. 2008; Shen. 2008; Zhou. 2008) have, as Robertson et al. pointed out only recently, not yet been confirmed in humans trials (Robertson. 2012). Moreover, the latest results from the Merck Reserach Lab show, contrary to previous evidence from the Cambridge Institute for Medical Research (Tolhorst. 2012), that even our current assumption with respect to the underlying mechanism, could at least be incomplete (Lin. 2012). This does not mean that the short chain fatty acids would not produce the desired increase in GLP-1 nad PYY, but rather that their effects are not solely mediated by  the aforementioned free fatty acid receptor in the gut.

Let's make things even more complicated and bring some long chain fatty acids to the table!

What is yet self-evident though is that the way GLP-1 and PYY modulate energy utilization punches yet another huge hole in the prostrated "calories in vs. calories out hypothesis", one that has little to nothing to o with insulin and one that acquires yet another shade of gray, when we look at the long-chain counterpart of the "bacterial excrements" the dreaded or beloved (depending on the standpoint of the individual) saturated fatty acids (SFA) and a recently published study by scientists from the Wageningen University in the Netherlands (De Wit. 2012), who investigated the long-term effects (8 week, study conducted on mice) of high fat diets with fats from different fat sources

• palm oil - representing the saturated fatty acids,
• olive oil - representing the mono-unsaturated fatty acids, and
• safflower oil - representing the polyunsaturated fatty acids

on body weight gain, liver triglycerides and the whole other standard parameters and their relation changes in the gut microbiome and the amount of fat that "left" the animals undigested.

Figure 1: Fecal fat and energy loss, total energy intake and relative (to control on normal chow) liver triglycerides, oral glucose tolerance and weight gain over the 8 week study period (de Wit. 2012)

A casual look at the data in figure 1 should suffice to see that there is a profound mismatch between almost all classic features of the metabolic syndrome of which we would usually expect that they would be closely associated:

• the rodents in the palm oil group ate the least amount of energy, excreted the greatest amount of fat and total energy in their feces and still gained the greatest amount of body weight and had the highest amount of liver triglycerides (beginning non-alcoholic fatty liver disease)
• the rodents in the olive oil group did not consume significantly more amount of energy or excrete significantly more amount of fat / energy in their feces and still gained ~40% less body weight and did not exhibit similarly high triglyceride storage in the liver as the rodents on the saturate fat (palm oil)
• the rodents in the safflower oil group were comparably ravenous (+20% energy intake), but although they did not excrete more energy and fat than their peers, their bosy weight gain was profoundly reduced and their liver triglycerides were better than in the "non high fat control group" and yet their glucose tolerance was not the best, but the worst of all the three groups

All that does only make sense, when a second parameter, or I should say another 100 trillion bacterial parameters come into play and the SFA induced reduction in microbial diversity and
composition (increased the firmicutes/bacteroidetes ratio) are accounted for, as well. those, this is at least what de Wit et al. believe are namely responsible for the complex changes in genes that regulate the fatty acid metabolism and expression of inflammatory markers, the scientists observed

Chicken or egg, cause of correlation? Or just gut optimization?

Even tde Wit et al. do yet point out that their observations do not provide significant evidence to establish a causal relationship between the bacterial changes, which are a direct result of an overflow of (selectively) antimicrobial saturated fats into the distal part of the intestine, the subsequent disturbances in the bacterial balance and (human!) gene expression in the gut and the  particularly pronounced obesogenic effects of saturated fatty acids.

You could, at least in my humble opinion, even argue that these are simply adaptive effects that ensure that the "host", in this case the rodents, "gets the most" out of his diet - after all, this is exactly what we are seeing here: A modulation of genes related to the conservation and storage of energy, such as the downregulation of the Bcmo 1 gene that predisposes to the development of obesity and non-alcoholic fatty liver disease (Hessel. 2008),  which allows for maximal energy efficiency despite greater fecal energy loss.

Conclusion? Drink safflower oil?

That these results should not be taken as an incentive to guzzle safflower oil (or drop your coconut oil for the latter) should be obvious. Just as obvious, by the way, as the realization that despite all the hoopla and my own excitement about the newly discovered importance of the gut microbiome as one of the possible contributers to the global obesity epidemic. We are understanding way too little about its interactions with its host, i.e. us, to exclude that we are not - yet again - confusing cause and effect, causation and correlation and take our gut microbiome, which is eventually nothing else than a mirror of our healthy or unhealthy lifestyle for the real deal, and try to modulate and fix the mirror image with anti-, pro- or prebiotics without working on what stands right before the mirror: The sedentary, convenience food consumer, who works to jobs and rather watches TV till late at night instead of getting his 7-8h of sleep....

References:

1. Aziz AA, Kenney LS, Goulet B, Abdel-Aal el-S. Dietary starch type affects body weight and glycemic control in freely fed but not energy-restricted obese rats. J Nutr. 2009 Oct;139(10):1881-9. Epub 2009 Aug 19. 
2. Hessel S, Eichinger A, Isken A, Amengual J, Hunzelmann S, Hoeller U, Elste V,  Hunziker W, Goralczyk R, Oberhauser V, von Lintig J, Wyss A. CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice. J Biol Chem. 2007 Nov 16;282(46):33553-61.
3. Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against  diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240.
4. Robertson MD. Dietary-resistant starch and glucose metabolism. Curr Opin Clin Nutr Metab Care. 2012 Jul;15(4):362-7. 
5. Shen L, Keenan MJ, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Zhou J. Dietary resistant starch increases hypothalamic POMC expression in rats. Obesity  (Silver Spring). 2009 Jan;17(1):40-5. Epub 2008 Oct 23.
6. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012 Feb;61(2):364-71.
7. Zhou J, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Shen L, Danna SC, Tripathy S, Hegsted M, Keenan MJ. Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6.
8. de Wit NJ, Derrien M, Bosch-Vermeulen H, Oosterink E, Keshtkar S, Duval C, de Vogel-van den Bosch J, Kleerebezem M, Müller M, van der Meer R. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am J Physiol Gastrointest Liver Physiol. 2012 Jun 14.
9. Zhou J, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Shen L, Danna SC, Tripathy S, Hegsted M, Keenan MJ. Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6. 

Pre-Workout Caffeine: Fat Liberator, Substrate Modulator, Trans-Fatty Acid Eliminator & Performance Upregulator! Do You Use it? Why are You Still no Ripped Olympian, Then?

Image 1 (mensfitnessandmore): I would not recommend to empty a whole can of "liquid animals", like bulls or horses, let alone monsters or other popular "creatures" from the kiosk next to your gym, if you don't want to crash from the sudden influx into and as rapid disappearance of sugar from your system - that's by the way what cyclists call "to bonk" and guess what, they do ingest tons of similar sugarwaters and -gels ;-)

You will be hard pressed these days to find a "caffeine free" fat burner. The few that are currently on the market lead a miserable existence, usually in the "on sale" or "expired" categories of everyone's favorite online shop. But do you really get more than just a transient spike of energy from taking a caffeine-based fat burner? According to a recently published study that was conducted by a team of international researchers from the University of Extremadura in Spain and the Australian Catholic University in Australia you do! Even without the addition of mostly useless in some cases potentially health hazardous (cf. "Natural Hormone Optimization Made Simple & Cheap: Avoid These 10 Anti-Androgens to Boost Testosterone & DHT") absorption amplifiers and all sorts of exotic herbs nobody actually knows what they are doing upon chronic ingestion, the 5mg/kg body weight of caffeine the 20 previously untrained men in the Olcina study ingested prior to an incremental maximal aerobic exercise protocol exerted a whole host of statistically significant effects - the active oxidation of fat, which is what you would expect from a "fat burner", was however not among them.

Caffeine is a potent fat liberator and substrate modulator

Given the fact that none of the currently available "fat burners" actively burns body fat, the statistically significant increase in lipolysis, i.e. the release of stored fatty acids into circulation, the increases in peak power, time to exhaustion and overall workout intensity, and the shift towards a higher rate of fatty acid oxidation Olcina et al. observed in their 20 untrained normal weight, young (20.9y), healthy men are not to be sneezed at, though (don't worry about the training status, caffeine is working for trained athletes, as well):

Figure 1: Performance and cardiovascular parameters during caffeine (5mg/kg) and placebo trial; all significantly (p<0.05) different (data adapted from Olcina. 2012)

After all, the combination of a harder workout (=greater total energy expenditure) and a relative increase in the amount of fatty acids that are used to fuel the workout will result in an increase in the total amount of fatty acids that are actually oxidized, so that caffeine does actually make a quite effective fat burning facilitator.

Does caffeine preferentially burn omega-3s and spare saturated fat?

For you as a SuppVersity student, all that ain't really news. What may however surprise you is that the effects of caffeine are not really indiscriminate as far as the type of fatty acids that get burned in the metabolic furnaces of your mitochondria are concerned.

Figure 2: Respiratory exchange ratio and changes in plasma fatty acid proportions after caffeine (5mg/kg) and placebo trial; all significantly (p<0.05) different (data adapted from Olcina. 2012)

In fact, Guillermo Olcina and his colleagues identified a distinct pattern as far as the (dis-)appearance rates of plasma fatty acids are concerned. Yet despite the fact that it looks as if the subjects had burned preferentally omega-3 fatty acids during the caffeine trial, this observation did not reach statistical significance due to the huge interpersonal variety (maybe a direct consequence of differences in omega-3 tissue content).

The increase in saturated fatty acids, on the other reached statistical significance, could however be a simple consequence of the aforementioned caffeine induced increases in lipolysis that was complemented by a proportional increase in stearic acid (C18:0) and a decrease in the mono-unsaturated fatty acid, trans-oleic fatty acid, which could potentially explain previous observations that caffeine reduces the risk of cardiovascular events (van Dam RM. 2008), since lower levels of trans-oleic acid (elaidic acid) show a clear association with increased risk of developing arteriosclerosis (Park. 2009).

Increase your performance, help fat loss - why does it not work for you?

Now all that sounds almost too good to be true. After all, you have been digging caffeine and harder stims for years now and still, you are neither ripped to shreds nor did you win a gold medal at the Olympics, right? Well, the reasons for that are manifold and I cannot possibly name them all in a single blogpost; the worst offenders are yet clearly:

• 

  As far as the issue of "stim tolerance" is concerned, it should still be mentioned that the study subjects consumed caffeine only occasionally and that I highly recommend to take regular times off your favorite pre-workout / stim. Also because the latter contain "other stuff" that does, in combination with caffeine and heavy workouts definitely puts you at a very high risk of overtaxing your sympathetic nervous system. Tired during the day, bad sleep, nightsweats, etc. are all certain signs that you have already passed by your chance to take time off.
  overtraining on stims and consequent downregulation / impairment of the sympathetic nervous system, often mistaken for "stim tolerance", of which previous allegedly short term (<2 weeks) withdrawl trials have shown that it may exist as far as the immediate and for some nasty side effects are concerned, but not with respect to the performance increases (cf. Van Soeren. 1998, Irwin. 2011) 
• not dieting when taking a fat burner so that the fat is simply restored to adipose tissue after its liberation / replaced by fat derived from the energy content of the foods you eat after your workout
• taking too much caffeine either at once or in the course of the day, subsequent chronic overexpression of cortisol, neurotransmitter depletion / irregularities and profound reductions of the testosterone to cortisol ratio (Beavon. 2008); optimal 200-300mg pre-workout (Desbrow. 2012); max. 400mg per dose, max. 600mg per day
• taking caffeine at the wrong time-point, usually too early, will have the plasma levels peak (90-150 min after ingestion; individual differences!), when your workout is long over done (best time to take caffeine for longer workouts is ~60min before exercise; cf. Skinner. 2012)

As you see there is reason that caffeine has always prevailed, even the good old mua huang (ephedra) based fat burners did their magic only in conjunction with mankind's favorite drug: Trimethylxanthine, a vegetable alkaloid crystallizing in white silky needles, found in the leaves and seeds of the coffee and tea plants, the leaves of guarana, maté and other plants and, of course, 99% of the fat burners your money can buy ;-)

References

1. Beaven CM, Hopkins WG, Hansen KT, Wood MR, Cronin JB, Lowe TE. Dose effect of caffeine on testosterone and cortisol responses to resistance exercise. Int J Sport Nutr Exerc Metab. 2008 Apr;18(2):131-41.
2. van Dam RM. Coffee consumption and risk of type 2 diabetes, cardiovascular diseases, and cancer. Appl Physiol Nutr Metab. 2008 Dec;33(6):1269-83.
3. Desbrow B, Biddulph C, Devlin B, Grant GD, Anoopkumar-Dukie S, Leveritt MD. The effects of different doses of caffeine on endurance cycling time trial performance. J Sports Sci. 2012;30(2):115-20.
4. Irwin C, Desbrow B, Ellis A, O'Keeffe B, Grant G, Leveritt M. Caffeine withdrawal and high-intensity endurance cycling performance. J Sports Sci. 2011 Mar;29(5):509-15.
5. Olcina G, Munoz D, Kemp J, Timon R, Maynar J, Caballero MJ, Maynar M. Total plasma fatty acid responses to maximal incremental exercise after caffeine ingestion. J Ex Sci Fi. 2012 June 4 [Epub ahead of print]
6. Park Y, Lim J, Kwon Y, Lee J. Correlation of erythrocyte fatty acid composition and dietary intakes with markers of atherosclerosis in patients with myocardial infarction. Nutr Res. 2009 Jun;29(6):391-6.
7. Skinner TL, Jenkins DG, Taaffe DR, Leveritt MD, Coombes JS. Coinciding exercise with peak serum caffeine does not improve cycling performance. J Sci Med Sport. 2012 May 31.
8. Van Soeren MH, Graham TE. Effect of caffeine on metabolism, exercise endurance, and catecholamine responses after withdrawal. J Appl Physiol. 1998 Oct;85(4):1493-501.