Docosahexaenoic Acid (DHA) Blunts Negative Side Effects of Conjugated Linoleic Acid (CLA) W/out Hampering Its Effects on Body Fat Loss & the Expression of Obesity Genes

She already knew what scientists have recently discovered and now confirmed: You better stack CLA and DHA if you want lean and health offspring ;-)

Conjugated linoleic acid (CLA) is not only an omega-6 fatty acid, it's also a trans-fat (though a natural one) and still even scientists believe that it could contribute to the solution of the diabesity epidemic, if it (a) finally yielded the same extreme fat loss (yep, just the blubber, nothing else) results in human beings as in rodents (cf. "CLA Annihilates Body Fat and Increases Endurance") and (b) anywhere near appropriate doses would not hold he risk of inducing fatty liver disease and insulin resistance (Clément. 2002). At least with respect to (b) a "bodybuilding approach" to CLA supplementation which is based on the "if hammering your head against the wall hurts, you better make sure you wear a helmet" principle of stacking CLA and PUFAs, esp. the long-chain omega-3 fatty acid DHA, has already yielded some promising results in a study that has been published earlier this year (Fedor. 2013a).

Since, the deposition of fat in the liver in response to CLA supplementation is in the end only the logical consequence of CLA's lipolytic (=fat releasing) and anti-lipogenic (=inhibition of fat storage) effects in the adipose tissue, the absence of adequate data on the amount of fat in adipose tissue and muscle or the fatty acid composition of liver, adipose tissue, and muscle, nor did we monitor the changes in the expression of genes involved in fatty acid metabolism in adipose tissue and muscle in the respective study did not allow for the conclusion that the co-supplementation of DHA would not blunt the beneficial fat loss effects of CLA, as well.

Is it possible that high dose DHA blunts the negative and the positive effects of CLA?

In a paper that's going to be published in the next issue of Metabolic Syndrome And Related Disorders Dawn M. Fedor et al. describe the results of a follow up study, which dealt with this very question and I guess I am not giving away more than what you will already inferred from the headline of this post, when I tell you that the answer to the question in the subheading is "No, DHA does not blunt the beneficial effects of conjugated linoleic acid on adipose tissue!"

Figure 1: Relative body weight, liver weight, periuterine fat mass, muscle weigh, liver total lipid weight, adipose total lipid weight, and muscle total lipid content of the mice after 4 weeks on a 0.5% CLA, 0.5% CLA + 1.5% DHA or 1.5% DHA diets expressed relative to respective data from mice on the standard chow (Fedor. 2013b)

If you take a closer look at the data in figure 1 you will realize that the provision of a diet that contained 0.5% CLA (only the "active", but potentially hazardous t10, c12 isomer was used in the study) and 1.5% DHA did not blunt the beneficial effects on total and periuterine body fat mass in eight-week-old, pathogen-free female C57BL/6N mice. On the other hand, it did mitigate the negative effects on liver weight and (and this is actually quite remarkable) had identical beneficial effects on liver fat as the DHA only diet.

DHA + CLA = perfect synergists

Although the "equation" above may sound as if I had taken it right from one of those shiny adds in a muscle mags, it does in fact look, as if the combination of CLA + DHA was the silver bullet for healthy body fat (and I repeat only body fat not lean mass!) reductions in the absence of any dietary and/or exercise interventions.

Figure 2: Expression of selected genes involved in the synthesis, storage and release of fatty acids from the adipose tissue; the respective values (in a.u.) of the control group were all 100, so you can thing of these as percentages, as well (Fedor. 2013)

Moreover, the analyses of the expression of pro- and anti-obesity genes in the adipose tissue does actually support this claim:

"CLA significantly decreased the expression of LXRb, PGC1a, PPARg, SREBP1C, ACOX1, and CD36 adipose mRNA when compared to the control group. We also observed a trend for CLA to decrease the expression of HSL (P=0.08). DHA was not able to prevent any of these decreases in gene expression. CLA significantly increased UCP2 mRNA expression when compared to control group; DHA again had no effect." (Fedor. 2013b)

If we translate all these acronyms the scientists use to describe the data I've plotted for you in figure 2 into plain cause and effect relations, we could simply state: CLA induced changes in the expression of genes in the adipose tissue of the rodents that would prevent the maturation of adipocytes and the synthesis and accumulation of fatty acids, while increasing their release into circulation,  and DHA did not effect these changes.

DHA takes care of the energy that's released / not stored in fat cells

What the co-administration of DHA did, however, was to prevent the deposition of the energy that was released, respectively not even stored in the adipocytes in the liver -- and it did that so effectively that the overall weight of the liver of the mice in the CLA + DHA group was not greater than the the liver weight of the rodents in the control group.

Figure 3: Liver fatty acid composition (µmol/g) and omega-3 : omega-6 ratio after 4 weeks on regular (control), 0.5% CLA, 0.5% CLA + 1.5% DHA and 1.5% DHA diets (Fedor. 2013b)

In fact, the co-administration of conjugated linoleic acid and DHA did even reduce the total fatty acid content of the liver (not to a statistically significant degree, though) and brought about profound changes in its fatty acid content - most prominently, a whopping +975% increase in the omega-3 : omega-6 ratio (see small graph in figure 3) that were even slightly more pronounced in the CLA + DHA group than in the DHA only group (you do remember that CLA is an omega-6 trans-fat, right?).

Finally a stack that works -- but will it work in humans, as well? 

I don't know if it dawned on you, already, but dairy and butter from grass cows already has both CLA and DHA in it - what a lucky coincidence, isn't it? Still, there is one downside: You simply cannot eat enough of it to get anywhere close to the human equivalents of the amounts that are used in rodent studies.

Now, although both the changes in body fat levels in the CLA + DHA group were consistent with those observed in the CLA only group and the effects of the combination treatment on the changes in hepatic fatty acid composition were consistent with those observed in the DHA only group, there is still one question we have to answer: Are we going to see similar esults in humans?

To be honest, I still cannot answer this question, but if you take into consideration that no previous human trial used dosages in the 20-30g range simply because that would be unethical given the associated side effects, we may soon get an answer to this question - as soon as scientists dare to slowly escalate the dosage, trusting on the ability of supplemental DHA to blunt the negative, while conserving the beneficial effects of CLA.


References:

• Clément L, Poirier H, Niot I, Bocher V, Guerre-Millo M, Krief S, Staels B, Besnard P. Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J Lipid Res. 2002 Sep;43(9):1400-9.
• Fedor DM, Adkins Y, Mackey BE, et al. Docosahexaenoic Acid prevents trans-10, cis-12-conjugated linoleic Acid-induced nonalcoholic Fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation.Metab Syndr Relat Disord. 2013a;10:175–180
• Fedor DM, Adkins Y, Newman JW, Mackey BE, Kelley DS. The Effect of Docosahexaenoic Acid on t10, c12-Conjugated Linoleic Acid-Induced Changes in Fatty Acid Composition of Mouse Liver, Adipose, and Muscle. Metab Syndr Relat Disord. 2013b Nov 21.

Get Lean & Stay Lean Quickie: OTC Fat Loss Supps Under Scrutiny. Sleepless Yet Lean in India?! Sesamine - Falsely Forgotten? High Carb Nighttime Snacks for Fridge Raiders?

Without an optimized dietary routine, a sound training plan and tons of discipline no fat burner is going to get you abs like these (suggested read: The SBSG Fat Loss Support Routine)

I suppose by today, the last remnants of your turkeys should be gone and you and your relatives ~0.5kg heavier (Hull. 2006). Against that background it appears only logical to turn this week's installment of On Short Notice into another Get Lean & Stay Lean Quickie. Moreover, with the 0.5kg the average American gains in the course of the Thanksgiving holidays, I already have my (or should I say your? Be honest ;-) figure of the week, so that there is actually no reason why we could not dive right into the science of fat loss.

As you are about to see, this installment has more ineffective than effective fat loss treats. Why? Well, maybe due to the fact that it harbors two studies on commercially available supplements? But whom am I telling this... you already know that the main benefits of these so-called "thermogenics" are actually related to their appetite suppressing and stimulating effects, which can help you stick to your diet and workout regimen, and not to their ability to actively "burn" body fat.

Apropos stimulant: Were you aware that there could be methamphetamine in a common ingredient of some thermogenics? No? I'd suggest you check out the last news of this Get Lean & Stay Lean Quickie first, then. If you are not interested in "scandalous" revelations of which you don't even know if they have a bearing on the extracts that are used in your favorite Acacia rigidula supplement (I would actually hope you don't have one, but anyway), you may obviously start at the top, as well:

• Weight loss stack fails to produce results: Caffeine + BCAA + CLA + Green tea = soy bean oil placebo (Thomas. 2013) At the 9th Annual ISSN Conference and Expo, Daniel Thomas and his co-workers  presented a study in which they investigated the effects an commercially available multi-ingredient dietary supplement containing 99mg of caffeine and a proprietary blend containing 1510 mg of CLA, green tea extract (45% EGCG), L-leucine, L-iso-leucine and L-valine in 22 obese volunteers (placebo arm: age, 34 ± 12; BMI, 34.1 ± 6.1; active arm: age, 36 ± 11.1 years; BMI, 30.0 ± 4.9).
  
  The supplement / placebo had to be taken with breakfast and lunch (with two pills per serving this would amount to 400mg of caffeine per day and an undisclosed amount of CLA, green tea and BCAAs, of which you can yet probably safely assume that they were underdosed). Body composition and android fat (dual-energy X-ray absorptiometry), waist and hip circumferences, blood pressure and heart rate were measured at baseline and after 8 weeks of supplementation. Aside from taking the supplement the participants were advised to stick to their regular dietary and activity patterns. Against that background it is not exactly surprising that the 'wonder pills' did not bring about any changes in body composition, android fat, waist or hip circumference; and in contrast to the acute effects of the  "hardcore" competition about which you can read in the last post of today's Get Lean & Stay Lean Quickie the product did not even increase the heart rate and blood pressure of the subjects.

• Blood sugar levels of Indian adolescents are not associated with insufficient sleep and yet not sleeping enough still takes its toll (Patel. 2013) -- You've read more than enough about the importance of sleep on the SuppVersity within the past couple of months (e.g. The SuppVersity Circadian Rythm Series) to be surprised by what Patel et al. conclude in the abstract of  their latest paper:
  

  "The current study indicates that inadequate sleep duration at night (<7 hrs) does not affect the blood glucose level of the Gujarati Indian adolescents of age group 13-20 years." (Patel. 2013)

  Unfortunately, this is yet again an instance where cursory skimming the abstract provides a  skewed image of the actual study results, which - as you can see in my plot of the actual results - did very well confirm previous observations of the same authors and the findings of the majority of studies which investigated the effects of insufficient sleep on body composition in Western adolescents.
  
  

  

  Figure 1: Body fat (%), fat free mass (FFM) and waist circumference in Indian adolescents (Patel. 2013)

  Statistically significant were the respective differences only in the male part of the study population. That's yet probably just a result of the low number of female participants which was not only significantly smaller (N=95 vs. N=237), but also very unevenly distributed as far as the ratio of female adolescents with adequate (N=90) and inadequate sleep (N=5) are concerned. Against that background you should also exert some caution with respect to the fat free mass values in the N=5 short sleepers. It would probably suffice to have one muscular athlete in this group to skew the whole results.
  
  Apropos "short sleepers": Can you imagine that only 14% of the male and 5% of the female Indian Gujarati adolescents actually didn't get their share of 7h+ sleep per day!? Makes me wonder about the number of smartphones, Playstations and cable TV channels in the Anand district where the 332 Gujarati adolescent school and and college students came from - the same goes for the respective interactions between nutrient quality, sleep duration and family income.

• Study shows addition of fish oil accentuates sesamin's 'fat burning effects' (Ide. 2013b) In what could be considered a follow up to the results of a previous study in which Ide et al. were able to show that the addition of arachidonic acid (ARA) to sesamin supplemented chow augmented body fat loss, and increased the expression of enzymes that are involved in the oxidation of fatty acids, Takashe Ide has just published another study, which shows that high dose fish oil (15-20g/kg chow) will illicit similar, if not even more pronounced effects on the expression of Carnitine palmitoyltransferase 2, which is necessary to transports fatty acids into the mitochondria, and the alpha and beta subunit of the trifunctional enzymes that are involved in their subsequent oxidation.
  
  

  

  Figure 2: Effects of Sesamin (SES) + fish oil or arachidonic acid (ARA) on mRNA expression of CPT, trifunctional enzymes alpha & beta, as well as serum lipids in rodents after 15/16 days on respective diets  (Ide. 2013a & 2013b)

  As the data in figure 2 goes to show you, these increases were accompanied physiologically relevant decreases in the concentrations of triglycerides, cholesterol and phospholipids in the blood of the 5-week old male Sprague Dawley rats, Ide used in his latest study. Moreover, the observation that the supplementation regimen enhanced increases in mRNA of the peroxisomal enzymes involved in fatty acid oxidation and
  a membrane protein (peroxin-11α) associated with peroxisomes without affecting enzymes associated with mitochondria and microsomal cytochrome P-450 4a1 expression indicates the "existence of a mechanism independent of PPARα to specifically induce the gene expression of peroxisomal proteins." (Ide. 2013b)  That's an unquestionably interesting observation; also because it could open up new avenues for the development of anti-diabesiety drugs or the identification of herbs and natural "fat burners".

• More scientific evidence: Eating carbs in the evening does not necessarily make you fat - even if you eat them instead of protein! (Eddy. 2013) While I would still be hesitant to recommend the ingestion of maltodextrin instead of casein or whey protein as a pre-bed snack, the results of a recent study by Eddy et al. clearly show that the sugar load right before bed did not have negative effects on the 59 sedentary, overweight and obese volunteers who were randomly assigned to ingest isocaloric amounts of maltodextrin (PLA), casein (CAS) or whey (WP) max. 30min before bed.
  

  

  Carbs Before Bed: What's good for overweight Israeli police cannot be bad for overweight Americans, can it? (photo by Mark Probst)

  "No significant group differences existed at baseline. There were no group x time interactions for RMR, hunger, satiety, desire to eat, fat mass, lean body mass, or weight (P< 0.05), although RMR displayed a trend towards significance with the PLA group decreasing by 74.3 ± 94.5 and WP and CP increasing by 235.73 ± 84.5 and 51.7 ± 79.4kcal/day, respectively (P=0.0559). Significant time effects were measured for satiety (pre: 31.5 ± 2.3, post: 40.6 ± 2.3, P< 0.008) and LBM (pre: 51.8 ± 0.1, post: 52.3 ± 0.1, P< 0.0001)." (Eddy. 2013)

  In view of the fact that it cannot be said if the absence of negative effects on hunger, satiety, desire to eat, fat mass, lean body mass, or weight was related to the obligatory supervised exercise sessions (3x/week; 2 days of resistance exercise and 1 day of high-intensity cardiovascular exercise) all participants had to attend, it does yet remain to be seen if similar results would be observed in obese (or lean?) subjects in the absence of a supervised resistance training and HIIT workouts. That said, as "non-significant" as the previously cited trend in resting metabolic rate ((RMR) may be, the increase in the amount of energy the obese subjects spent sitting around in both protein groups and the contrasting decrease in the maltodextrin group, is something to keep in mind .

  

  Ok, nighttime snacking increases LDL, but if you measure it in the morning after a high carb + high fat  snack that alone can contribute to the statistically "significant", but physiologically irrelevant LDL increase of 7mg/dL the scientists observed in their 11 healthy participants.

  Midnight snacking (Hibi. 2013): Whether eating right before bed is a good idea at all was not addressed in the study at hand and according to an even more recent paper by Hibi et al., postponing your 10am 192kcal snack (mean protein : fat : carbohydrate ratio of 5:50:45) to 11PM will significantly decrease fat oxidation (daytime snacking: 52.0 ± 13.6 g/d; nighttime snacking: 45.8 ± 14.0 g/d; P = 0.02) and increase total and LDL cholesterol significantly. How bad that actually is, is however likewise questionable, after all the blood glucose and insulin levels, snack and total energy intake, body weight, and energy expenditure of the 11 healthy women (age: 23±1 y; body mass index: 20.6 ± 2.6 kg/m²) who participated in the randomized-crossover trial were not affected by the switch from the daytime to the nighttime snack.
  Irrespective of any trends and non-significant differences, eating a heap of pure sugar (~35g - this is based on the assumption that the amounts were identical to another recent study by the same group which tested the acute effects of carbs and protein, cf. Kinsey. 2013) before going to bed has little to nothing to do with having a whole meal, with or without carbohydrates before bed -- and that this can increase not hamper weight loss, is something you as a SuppVersity reader are well aware of (see "Carbs after 6PM Will Make You Lean" & "Carbs After 6PM Reloaded").

• 

  Figure 3: According to a somwhat dubious study Acacia rigidula contains more than 44 "toxic amines and alkaloids" (data in ppm; Clement. 1998)

  Hi Tech Pharmaceuticals sponsored trial finds: Fastin RX is better than only two of its ingredients (Jacobs. 2013) -- I guess you won't be surprised to hear that the addition of  methlsynephrine, 1,3 dimethylamylamine ("geranium extract"), yohimbine HCL, naringen and theobromine to caffeine and Acacia rigidula extract potentiates the effects of either 300 mg caffeine (C) or 250 mg Acacia rigidula (AC) alone or in combination, right?
  
  Fine, 'cause this leaves more room for the important question, whether an additional increase in heart rate of 6.9 and 6.0bpm 2h and 3h after the ingestion of the extended release "fat burner" Fastin RX, a significant increase in systolic blood pressure of 33%, 26% and 19%, as well as increases in diastolic blood pressure that were 16.6%, 2.9% and 15% higher than in the caffeine (only) trial have any bearing on the efficacy of this product, when the 10.1%, 10.0% and 4% greater VO2 consumption (compared to AC and C, only) in the first three hours after the ingestion of the diet pill did no not show any significant main or interaction effects on resting metabolic rate? Probably not? Yeah... I would guess so, as well.

That's it for today... aside from the advice not to freak out over whatever amount of weight you may have gained in the past couple of days, I shold say: Trust me, it's not worth stressing yourself this is just going to make things worse. Just return to your regular nutritional habits, keep working out and it will be gone in no time. I'd also suggest you check out the latest  SuppVersity Facebook News on

• Aqueous dried barberry extract as a treat for acne vulgaris (learn more)
• Zinc + phytoestrogens vs. osteoporosis - a double- yet dull-edged sword  (learn more)
• Cold-water immersion beats passive recovery and contrast water therapy for recovery after an intense American football training (learn more)
• Study from the Boston University School of Medicine says: Female adolescents don't eat enough meat. (learn more)

and the other news I posted today and am going to post in the course of the next 24h. I guess that should suffice to bridge the time until I post tomorrow's full-length SuppVersity article. I'll see you tomorrow, then!

References:

• Clement BA, Goff CM, Forbes TDA. Toxic amines and alkaloids from acacia rigidula. Phytochemistry, Volume 49, Issue 5, 5 November 1998, Pages 1377–1380. 
• Hibi M, Masumoto A, Naito Y, Kiuchi K, Yoshimoto Y, Matsumoto M, Katashima M, Oka J, Ikemoto S. Nighttime snacking reduces whole body fat oxidation and increases LDL cholesterol in healthy young women. Am J Physiol Regul Integr Comp Physiol. 2013 Nov 21.
• Hull HR, Hester CN, Fields DA. The effect of the holiday season on body weight and composition in college students. Nutr Metab (Lond). 2006 Dec 28;3:44.
• Ide T, Ono Y, Kawashima H, Kiso Y. Interrelated effects of dihomo-γ-linolenic and arachidonic acids, and sesamin on hepatic fatty acid synthesis and oxidation in rats. Br J Nutr. 2013a Feb 28:1-14.
• Ide, T. Fish oil at low dietary levels enhances physiological activity of sesamin to increase hepatic fatty acid oxidation in rats. Journal of Clinical Biochemistry and Nutrition. 2013b; 51(3):241–247.
• Jacobs PL. Acute physiological effects of the commercially available weight loss/energy product, Fastin-XR®, in contrast with the individual effects of caffeine and acacia rigidula. Journal of the International Society of Sports Nutrition 2013, 9(Suppl 1):P10.
• Kinseyet al.: The effect of acute ingestion of a protein beverage consumed late in the evening on metabolism, appetite, mood state, and blood lipid in overweight and obese adults. Journal of the International Society of Sports Nutrition. 2013; 9(Suppl 1):P16.
• Patel MC, Shaikh WA, Singh AS. Association of sleep duration with blood glucose level of gujarati indian adolescents. Indian J Physiol Pharmacol 2013; 56(3):229–233.
• Thomas DD, Rawal S, Kinsey AW, Eddy WE, Fisher N, Spicer MM, Ormsbee MJ. The combination of green tea, caffeine, conjugated linoleic acid and branched chain amino acids have no effect on body composition and abdominal fat changes in overweight and obese men and women. Journal of the International Society of Sports Nutrition. 2013; 9(Suppl 1):P29

A Higher Intake of CLA and Vaccenic Acid from Dairy, Beef, Veal and Lamp Could Prevent Subtle Weight Gain in Healthy Middle-Aged Individuals. Is 1.5g/day the Magic Number?

A dairy cow: Does her stomach hold the key to a leaner, healthier life or are CLA and vaccenic acid, the ruminant trans-fatty acids just as bad as their grainy cousins?

There are supplements that work and supplements that don't work and then there are those supplements, where nobody can actually tell, whether they belong to the former or the latter category. Conjugated linoleic acid, the ruminant omega-6 trans-fat you will find at particularly high concentrations in milk and meat products from grassfed dairy, unquestionably belongs to the latter category. While we do actually have plenty of in parts almost unsettlingly impressive rodent data (e.g. "CLA Destroys Body Fat & Increases Endurance! But at Which Costs?"), the outcomes of independent  controlled human studies are equivocal; with results ranging from "total failure", to "promising, but not half as impressive as we have expected based on previous rodent studies".

That being said, I was quite intrigued, when I hit onto a recently published study that takes a novel angle on the whole CLA for weight loss issue. One I usually don't like, as it involves a lot of statistical shenanigan, but still appears appropriate in this particular case, where the controlled small scale trials are failing us.

The Nordic Men (and women) love their full-fat dairy - rightly so?

If you are a loyal reader of the SuppVersity, who does not just read the detailed elaborations here on www.suppversity.com, but is also following the latest short news on the SuppVersity Facebook Wall, it probably won't surprise you that the study which is going to be published in the October issue of the European Journal of Clinical Nutrition has been conducted in Northern Europe. After all, you will have noticed that many of the interesting short news items relating to (larger scale) studies on the effects of one or another of the "bad fats" are conducted at universities and research centers in Sweden, Finland, Norway and, as in this case, Denmark - at the Aarhus University, to be precise, where Hansen and his colleagues datasets from the Diet, Cancer and Health study from December 1993 to May 1997. The participants, 160,725 men and women, aged 50–64 years, who were all born in Denmark and had been living in the greater Aarhus or Copenhagen areas, had all completed detailed food frequency questionnaire (FFQ) and a self-administered lifestyle questionnaire, before they underwent a physical examination and a follow up 5-6 years later.

How did the scientists know how much CLA and vaccinic acid the individual food items contained? unfortunately, they didn't. The way by which they calculated / estimated it,  i.e, by combining the content of r-TFAs in milk fat (data based on another Danish study) with the content of milk fat in dairy products given by the Danish food composition tables and using the values of r-TFA content in ruminant meat products representative of the supply in Denmark, does however make sense to me. The resulting averages should therefore be relatively reliable.

Based on the 77 food items of the food frequency questionnaires which contained ruminant trans-fatty acids R-TFA (this includes both CLA, as well as vaccinic acid which can be converted to CLA in the human body; cf. Turpeinen. 2002), i.e.

• dairy products (n=63), 
• ruminant meat products (beef, veal or lamb) (n=2), and
• composite recipes containing both dairy and ruminant meat (n=12) 

Hansen et al. calculated the average r-TFA intake of each of the 57053 subjects with complete datasets and correlated them with the participants changes in body weight and waist circumference (WC) over the 5-year period to the follow-up.

A massive amount of data suggest minimal amounts of r-TFA are necessary

As the subheading to this paragraph already reveals, the result of the all this statistical shenanigan suggest that the ruminant trans-fatty acid intake from foods, not supplements, does have a beneficial effect on the change in total body weight (an ameliorating effect on weight gain, to be precise).

Figure 1: Absolute intake of ruminant R-TFA (in g/day) and changes in weight; adjustment for sex, age, height, baseline weight, smoking, alcohol intake, education, weighted intake of foods containing high amounts of I-TFA (g/day) and in women, menopausal status and hormone replacement therapy (Hansen. 2013).

A brief glance at the graphs in figure 1 will yet also tell you that their effect on body fatness (as indicated by changes in visceral adipose tissue), is negligible, not to say non-existent. In a way you may say that this is a good thing, because the turning point at a daily r-TFA intake of >1.5g/day, where the restricted cubic spline (that's a statistical fit into the data; figure 1, solid lines) seems to indicate that r-TFA intakes of more than 1.5g/day would precipitate weight gain, is thus absent as well.

Figure 2: Relative intake of R-TFA (in % of total energy intake) and changes in waist circumference. Solid lines: restricted cubic spline with five knots; Dashed lines: 95% confidence interval; same adjustments as in figure 1(Hansen. 2013)

In addition, if we do also consider total energy consumption and the contribution of r-TFAs to the latter (see figure 2), it becomes obvious that we cannot neglect the profound widening of the 95% confidence interval in figure 1 (dashed lines), which tells us that some of the high r-TFA consumers did get even leaner, while others did gain a significant amount of weight. Adjusted for caloric intake and the other confounding variables this effect vanishes and a trend towards lower / even no body weight gain in high r-TFA consumers becomes visible (even within the higher intakes, where the confidence interval widens, due to the lower number of participants, but does not change the general trend). The beneficial effect on waist circumference, however, remains negligible.

So what, if anything, can we learn from these results?

At first sight, the results of the study at hand seem to stand in line with what you have read in "Fat Advantage: 61% Lower Rates of Metabolic Syndrome in High Fat Dairy Lovers", here at the SuppVersity exactly one week ago. It even appears to provide a mechanism by which the high fat dairy products could exert their highly desirable anti-obesity effects, if the high CLA + vaccenic acid (r-TFAs) consumers in the Hansen study were not just the subjects who gained the least weight (measured against their nutrient intake and adjusted for all sort of other confounding factors), but also those with the lowest increase in visceral adipose tissue.  

If that were the case, however, the graph on the right hand side of figure 2 should have at least some kind of slope. Since it hasn't, we must assume that the beneficial health effects of r-TFAs are either (a) not brought about by changes in visceral obesity, (b) the latter are not appropriately quantified by simply measuring the waist circumference or (c) in view of the fact that we are not talking about "weight loss", but rather a prevention of the (partly probably age induced) increase in weight gain a stable waist circumference has to be considered a "success", already.

The scale is an unreliable tool to judge visceral obesity. And even a measuring tape can be misleading, if you are really "skinny fat".

Personally, I tend towards a combination of all three. First of all even moderate weight gain has been shown to increase the risk of impeding metabolic syndrome. The weight stability over >5years in the high r-TFA consumers must therefore be considered to be prognostic of a lower risk of metabolic syndrome. Secondly, visceral does not necessarily equal abdominal fat. Especially in older individuals the gynoid fat areas contribute to visceral obesity, as well. Moreover, we all know the skinny fats, men and women with a relatively large amount of highly inflammatory visceral fat and normal or even low waist circumferences also known as "normal weight obese"; cf. Romero-Corral. 2010).

And thirdly and most importantly: Weight loss is mainly an issue for people who are already overweight or obese. For best-agers who are still in form (and in Denmark there are such people ;-), success is better defined by maintaining the muscle mass you have, not accumulating additional (visceral) body fat and leading an overall healthy lifestyle. That ruminant trans-fatty acids can, maybe even should be a part of the dietary side of this healthy life-style is therefore the main take home message of this study.

What should not be forgotten, however, is the fact that this study was at least in parts supported by the Danish Dairy Research Foundation, certainly not an organization with a particular interest in "bad news" on vaccenic acid, conjugated linoleic acid and dairy products in general, right?


References:

• Hansen CP, Berentzen TL, Halkjær J, Tjønneland A, Sørensen TI, Overvad K, Jakobsen MU. Intake of ruminant trans fatty acids and changes in body weight and waist circumference. Eur J Clin Nutr. 2013 Oct;66(10):1104-9. doi: 10.1038/ejcn.2013.87.
• Romero-Corral A, Somers VK, Sierra-Johnson J, Korenfeld Y, Boarin S, Korinek J, Jensen MD, Parati G, Lopez-Jimenez F. Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J. 2010 Mar;31(6):737-46.
• Turpeinen AM, Mutanen M, Aro A, Salminen I, Basu S, Palmquist DL et al. Bioconversion of vaccenic acid to conjugated linoleic acid in humans.Am J Clin Nutr2002;76: 504–510.

2.1kg Muscle From Fast Food Supplement; No Prolactin, No Fat; Oleic Acid Counters CLA's Inflammatory Effect; Spicy Marinades vs. Salmonella; Flaxseed, Estrogen & Penis Size; TTA in the Emergency Room; Alcohol & Binge Eating

Image 1: Scientifically proven muscle builder - 2.1kg lean mass in 3 months, no post-cycle therapy necessary!

I was just about to write another one of my artistic introductions, trying to incorporate all the exciting On Short Notice news I've piled up for you into a brief narrative, when I realized that you probably don't really appreciate those introductions (I guess, I would skip them myself, so don't worry, this is more of an objective assessment than an accusation). So, I listened to my gut and decided to skip this part of this series, today, and rather spend the time to edit another item I did actually not want to post today. It's the one on the "IIFYM slightly gone wrong fast food bulk" in the Hambre study, to be precise; and I would venture the guess that you won't mind taking that instead of a longer introduction, once you've read and digested the impossible: You cannot only gain muscle with "fast food supplements", you won't even get fatter than you would if you just used a classic whey protein... oh my, I see, you are already scrolling down: What I said, I would have been wasting my time, had I written a longer introduction. But dare you, if you don't at least read the other items, as well!

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  Figure 1: Food intake (top, lef) and energy expenditure (bottom, left) as well as body fat % (top, right) and body weight development of the normal vs. prolactin negative mice after 14 weeks on standard chow (SC) or high fat diet (HFD; Auffret. 2013); btw: taking super-doses of vit. B6 will induce nerve damage, not fat loss!

  Without prolactin mice can't get fat! If that is true for humans as well, this would mean that Julien Auffret and his colleagues would have made a very important finding that could help us solve at least part of the diabesity pandemic, if we found a way to mimick the effects the "beigening" (=making white adipose tissue behae similar to the fact burning brown adipose tissue) effect the genetic ablation of the prolactin receptor on the fat cells of the mice in the Auffret study had on their susceptibility to diet induced obesity (Auffret. 2013).
  In particular, the scientists found that the ablation of the prolactin receptor gene in the mice results in profound increases in the expression of master genes controlling brown adipocyte fate (PRDM16) and mitochondrial function (PGC1α, UCP1), which allow - and this is the actual caveat,, here - for an inrease in thermogenesis.
  The latter, in turn, allows the rodents to burn off a major part of the fat they would otherwise store and thus keeps them relatively lean despite HFD feeding. Aside from the fact that the hyperphagic rodents on the high fat diet were still fat (there is no debating that!), you may savely assume that the effects will be way less pronounced in human beings, where 9/10 "thermogenic" agents that have been successfully tested in rodents do nothing at all, anyway. Against that background the hunger-promoting effects of the prolactin recetor ablation would suggest that it is almost as likely that a drug that block prolactin completely would make obese individiuals even fatter, since that's usually what happens if you eat more - like the mice in the prolactin (-/-) group did (see figure figure 1), without burning more.

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  Figure 2: Comparison of MUFA : CLA ratios in steak and mince from grass fed or conventional beef and milk from mares, sows, women (human milk ;-), goats and cows (based on Dhiman. 1999; Jahreis. 1999; McAfee. 2011); higher values indicate more MUFA per unit of CLA, but more must not necessarily be better - in fact too much MUFA could completely block the fat loss effects of CLA and thus maybe explain why it rarely works in humans - our diets are pretty high in oleic acid and thus the ratio will be much lower, than in the high dose CLA rodent trials

  Conjugated linoleic acid needs oleic acid to work without side effects. That's the main take-home message from a recent study conducted by researchers at the at the University of North Carolina at Greensboro, who found that oleic acid, the mono-unsaturated fatty acid from olive oil & co, does prevent the expression of inflammatory genes in adipocytes treated with the "anti-fat fat CLA"..
  So, until my friends from the supplement industry read this post and come out with yet another SuppVersity science powered product with CLA in olive oil* you simply make sure to have a spoon of the liquid gold from time to time, when you feel that you need to take CLA to burn more fat. Unfortunately, this could not just mean that you can rid yourself of the nasty side-effects as discussed in "CLA Destroys Body Fat! But at Which Costs?", but also that the "body fat destruction" will at least be ameliorated if not totally absent :-(
  * I had hardly written this post, when I browsed the web and found that a certain newcomer and as of late very succesful "yellowish green" company has already a CLA + Olive Oil + Avocado Oil combination on the market, for them this would mean that they didn't even have to change their formula

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  Image 2: It's funny how so many things people (or at least chefs) have been doing forever, here marinating meats, simply make sense, isn't it?

  Antibacterial marinades for your meat! Don't worry this is not yet another dysfunctional functional food that's going to make you sick, but an all-natural mixture of green tea, lemon and turmeric you will have to smear onto your chicken meat if you want to make sure to get rid of the C. jejuni and S. enteritidis it may be contaminated with.
  All it takes are 24h of "incubation", but that's nothing else than leaving your meat lying in the marinade in your fridge and thus something you would do anyway, right? That's what I would call a convenient, effective and above all totally natural and healthy way of gettting rid of Samonella and Campylobacter :-)
• Tons Flaxseed flour in your diet will increase estrogen, but won't decrease the size of your penis, well at least not visible ;-) That's probably the most straight-forward summary of the results, Ludmila Ferreira Medeiros de França Cardozo and her colleagues present in the latest issue of Food and Chemical Toxicology after analyzing the effect of a flaxseed flour containing diet on the expression of hormone levels and penis morphology of male rats (de Franca. 2013)

  

  Image 3: Flaxseed bread won't turn you into an hermaphrodite overnight, don't worry.

  While the rats that were maintained on a diet containing 25g of flaxseed flour per 100g for 250days had significantly elevated estrogen levels in the blood 39.5 vs. 32.5 pg/mL (+22%), the minor drop in testosterone did not reach statistical significance and the reduced diameter of the corpus spongiosum, which helps to maintain the urethea as a viable channel for the ejaculation was obviously no problem for the fertility, either - at least the scientist don't mention anything in this regard; unfortunately, they did not really test it, either, as the poor male Wistar rats that were abused in this experiment were bachelors against their will.
  In view of the fact that flaxseed ain't the best source of omega-3s, anyway, and there appears no other good reason (for men and women!) why you would eat them in large quantities (I am not talking about the occasional tablespoon of flaxseed, here), I would still suggest to stay away from it.

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  Image 4: In farm-raised salmon chronic TTA administration has been shown to improve cardiac function and immune activity; it does however also lead to cardiac growth during viral infections, so that the benefits of chronic administration are still by no means certain (Grammes. 2013a & 2013b); long-term human studies, on the other hand, are not yet available.

  Acute TTA administration soothes the flames and keeps the coronary vessel open You will unquestionably remember my previous posts about the fat burning fatty acid tetradecylthioacetic acid (TTA) and how it's ability to accumulate in various tissues of your body could potentially become problematic. In the short term however, it's anti-inflammatory effects can come very handy. So handy, in fact, that the a recently published study by Pettersen et al. would suggest that we are soon going to see TTA balloons being inserted into coronary vessel walls, in order to deliver the sulfur-containing fatty acid right to an obstructed vessel that's being operated on, in order to suppress the local expression of inflammatory cytokines, as well as the subsequent macrophage infiltration and the unwanted collagen formation, which would precipitate restenosis (=further clogging) of the very heart vessel that has only just been opened operatively.
  You may now rightly ask yourself what this has got to do with you? Well, if it works locally, it could work similarly systemically and other studies such as Bjørndal (2013) do confirm just that: 0.4% TTA reduce TNF-α, IL-1β, and IL-6 in an experimental model of colitis and render the rodents guts more of less bullet..., ah, pardon, dextran sulfate sodium (DSS; a chemical used to induce cholitis) proof. The long-term effects of the continous consumption of ~3g of TTA, which would be the human equavalent of those 0.4% TTA in the rodent diets is yet still not fully established (re-read: "TTA & Fish Oil" and "TTA & Fish Oil - Revisited").

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  Figure 3: Alcohol overrides the inhibitory control over food intake (Chapman. 2013)

  Of TV watching, sleep deprivation and alcohol consumption, booze has the most pronounced negative effect on reward saliency and inhibitory control of food intake! That's the conclusion Colin Daniel Chapman, Christian Benedict, Samantha Jane Brooks, and Helgi Birgir Schiöth mkae based on their latest meta-review of pertinent studies from pubmed (N=23). With an impact factor of 1.03 on a scale from -4 to 4, alcohol is by far the worst the greatest effect on food intake and shows the highest correlation with obesity (Chapman. 2013).
  Compared to booze, both sleep deprivation (50% less) and TV watching (20% less) appear almost harmless. Their contribution in the non-drinking part of the population may yet still not be underestimated, also because the urge to do the latter, i.e. watch TV, when you ought tho sleep, precipitates the former and subsequent derangements in the circadian rhythm (suggested read: "The SuppVersity Circadian Rhythm Series").
• IIFYM was yesterday, ROWFYM is today, but what's going to be tomorrow? If that's all Greek to you, let me first bring you in the loop on the acronyms. While IIFYM designates "If It Fits Your Macros", implies (in the most extreme case) that you give a sh*t about what you eat, as long as you hit your macronutrient ratios for the day ("Carbs? Gimme that pizza!") and is getting increasingly popular among those who are fed up with broccoli and chicken breast and either unwilling or unable to see that those are not the only, and I would say, by far not the most healthy foods you can eat, ROWFYM is my own invention, means "Regardless Of Whether It Fits Your Macros" and would probably end up for way too many trainees in a protocol similar to the one 12 of the 24 subjects in a recent study from the Linköping University in Sweden were following for 12 weeks (Hambre. 2013).

  

  Image 5: "WTF do you want, I am doing ROWIFYM, here! That's serious bulking, man. Scientifically validated." If you want to follow his example, go ahead... but 3 months really is the absolute max and only if you are still healthy - regardless of whether the blood markers return to normal in the course of your next diet.

  While those lucky (?) twelve healthy young men (aged 19–32 years) in what I will from now on call the "fast-food arm" of the study had to add a delicious (???) fast food menu (1350 kcal, 41 g protein) on top of their diets, the other twelve participants had to contend themselves with a blatant protein shake (33g of whey) as their bulking supplement of choice. The reasoning behind this at first sight unquestionably highly questionable experiment was that the Swedish scientists wanted to elucidate, whether it would really make a difference whether you are eating "clean" (=adding a whey protein shake) or simply stuffing yourself with the next best, allegedly protein-laden fast food you can find during a 3-months bulking cycle (at least three lifting sessions per week) and the results were, ... well, let's say surprising.
  As you would expect, subjects in both groups managed to gain some weight. The first surprise is that subjects in both groups gained identical amounts of weight, namely 3.6kg. That's not all, however. Even the lean mass increases 2.1kg did not differ between the groups (measure by DEXA scans) and the sophisticated (compared to a similar calories in vs. calories out calculation) measurement of the resting metabolic rate, the scientists had conducted yielded that both groups had compensated for the overeating by a statistically highly significant (p < 0.0001!) + 10% increase in resting metabolic rate!

  

  Figure 4: Kaplan-Meier plots indicating the percentage of patients that made it to time-point X (see horizontal axes) without adverse event after their first coronary event - patients w/ (thin line) vs. w/out (bold line) metabolic syndrome (top), patients with high (thin line) vs. low (bold line) ApoB leves (bottom; based on Corsetti. 2005); ApoB turns out to be a way better risk predictor than having metabolic syndrome

  Before you do now jump into your car and head for the next drive-in "restaurant" with a big yellow "M" in front of it, you may want to take into consideration that this extended ROWIFYM version of the IIFYM approach, where you may hit the protein but overshoot on the carbs and fats (and certainly not  the good ones), did lead to statistically significant increases in fasting insulin and ApoB, a building block of LDL that has been associated with increased risk of arterial plaque formation (Gebel. 2008), compared to the "clean bulk" (= whey only) group. And while those changes (as well as the increase in RMR) were reversed on the 12 months follow-up, I am not sure if especially those people, who are most fond of bulking approaches like that, i.e. men (and very rarely women) who have been following a junk food diet for way too long already, should take the results of this study as an incentive to do a 3-month fast food bulk during the winter. After all, it could be that one additional LDL molecule that nests in the already existent arterial plaque which will eventually break the camel's, no your neck - or for those who like it more explicitly, which won't let the next mini blood clot pass by and causes a stroke, which could, in the worst case, end deadly!

That's it as far as the official On Short Notice items go, for today. If you don't have enough yet, I suggest you take a glance at the 6-10 news-items I've piled up on the SuppVersity Facebook Wall for you to review. Maybe you've read that sleeping with wife and children in a room would decrease your testosterone levels? False! Maybe it decreases the intellectual capacity of the reporter who wrote the respective news-item you may have read, but what really happens, is an increase in the amplitude of the circadian pattern with higher morning and lower evening testosterone levels (click here to read more). And if you neither have or plan to have children or don't care about your or your significant other's testosterone levels, you may be interested in a study that debunks the use of a "slim belt" for weight loss purposes, the idiotic idea to counter BPA toxicity with soy, the way working out can make depressed old people happy again, and more... ah, I almost forgot, there will also be an exercise special of On Short Notice very soon - and I am not talking about next Saturday, here - so stay tuned, it could be published anytime (Tip: If you subscribe to the SuppVersity Facebook Page you won't miss it ;-)

 References:

• Auffret J, Viengchareun S, Carré N, Denis RG, Magnan C, Marie PY, Muscat A, Fève B, Lombès M, Binart N. Beige differentiation of adipose depots in mice lacking prolactin receptor protects against high-fat-diet-induced obesity. FASEB J. 2013 Sep;26(9):3728-37. 
• Bjørndal B, Grimstad T, Cacabelos D, Nylund K, Aasprong OG, Omdal R, Portero-Otin M, Pamplona R, Lied GA, Hausken T, Berge RK. Tetradecylthioacetic Acid Attenuates Inflammation and Has Antioxidative Potential During Experimental Colitis in Rats. Dig Dis Sci. 2013 Aug 2.
• Chapman CD, Benedict C, Brooks SJ, Birgir Schiöth H. Lifestyle determinants of the drive to eat: a meta-analysis. Am J Clin Nutr. 2013 Sep;96(3):492-7. Epub 2013 Jul 25.  
• Corsetti JP, Zareba W, Moss AJ, Sparks CE. Apolipoprotein B determines risk for recurrent coronary events in postinfarction patients with metabolic syndrome. Atherosclerosis. 2004 Dec;177(2):367-73.
• de França Cardozo LF, Boaventura GT, Brant LH, Pereira VA, Velarde LG, Chagas MA. Prolonged consumption of flaxseed flour increases the 17β-estradiol hormone without causing adverse effects on the histomorphology of Wistar rats' penis. Food Chem Toxicol. 2013 Aug 25.
• Dhiman TR, Anand GR, Satter LD, Pariza MW. Conjugated linoleic acid content of milk from cows fed different diets. J Dairy Sci. 1999 Oct;82(10):2146-56.
• Gebel E. Meet LDL's partner in plaque. ApoB puts the "bad" in bad cholesterol. Diabetes Forecast. 2008 May;61(5):39-40.
• Grammes F, Rørvik KA, Takle H. Tetradecylthioacetic acid modulates cardiac transcription in Atlantic salmon, Salmo salar L., suffering heart and skeletalmuscle inflammation. J Fish Dis. 2013a Feb;35(2):109-17. 
• Grammes F, Rørvik KA, Thomassen MS, Berge RK, Takle H. Genome wide response to dietary tetradecylthioacetic acid supplementation in the heart of Atlantic Salmon (Salmo salar L.). BMC Genomics. 2013n May 11;13(1):180.
• Hambre D, Vergara M, Lood Y, Bachrach-Lindström M, Lindström T, Nystrom FH. A randomized trial of protein supplementation compared with extra fast food on the effects of resistance training to increase metabolism. Scand J Clin Lab Invest. 2013 Aug 30.
• Jahreis G, Fritsche J, Möckel P, Schöne F, Möller U, Steinhart H. The potential anticarcinogenic conjugated linoleic acid, cis-9,trans-11 C18:2, in milk of different species: Cow, goat, ewe, sow, mare, woman. Nutrition Research. October 1999; 19:10. 1541–1549.
• McAfee AJ, McSorley EM, Cuskelly GJ, Fearon AM, Moss BW, Beattie JA, Wallace JM, Bonham MP, Strain JJ. Red meat from animals offered a grass diet increases plasma and platelet n-3 PUFA in healthy consumers. Br J Nutr. 2011 Jan;105(1):80-9.
• Murali N, Kumar-Phillips NS, Rath NC, Marcy J, Slavik MF. Effect of Marinating Chicken Meat with Lemon, Green Tea and Turmeric Against Foodborne Bacterial Pathogens.International Journal of Poultry Science. 2013; 11(5): 326-332.
• Pettersen RJ, Salem M, Rotevatn S, Kuiper KK, Larsen TH, Bohov P, Berge RK, Nordrehaug JE. Effects of local delivery of Tetradecylthioacetic acid within the injured coronary vessel wall. Scand Cardiovasc J. 2013 Aug 30.
• Reardon M, Gobern S, Martinez K, Shen W, Reid T, McIntosh M. Oleic Acid Attenuates trans-10,cis-12 Conjugated Linoleic Acid-Mediated Inflammatory Gene Expression in Human Adipocytes. Lipids. 2013 Sep 2.

On Short Notice: Retinoic Acid vs. Lung Cancer / Metabolic Effect of Fats in Cerebral Fluid / Nucleotid Supplements Instead of Icepacks // Ibuprofen & Leaky Gut / Fish Oil Enema & Colitis / Fructose, Glut-5 & Obesity + More!

Image 1 (Coloribus): Unquestionably a great add, but the (Ex-)Marlboro man would be better off with a piece of liver than a carrot ;-)

Just as I promised I am pumping out another set of "short notice" items. To make sure not to be confused with what I have once heard someone call a "pubmed warrior", I did however spike today's episode with three longer items and saved a couple of mini-items for the next week. I hope you enjoy the ride and don't forget to copy "Fatfree" who asked for more in-depth info on TUDCA after reading last Saturday's installment of this series (see "Testosterone - 12% Drop With 75g Glucose? Low T3 Syndrome - Can TUDCA Help?"). If there is more information that would make a longer post worthwhile and I find the topic interesting enough to spent the time on doing the research, I am always willing to comply with wishes like this :-)

Retinoic acid (not beta carotene!) can protect smokers from lung cancer

In a paper that has just been published in the Journal of Food Sciences, Xue et al. report that the epigenetic switches retinoic acid (active, real vitamin A) triggers in cancer cells of lung cells in cigarette-smoke exposed rodents does effectively counter the upregulation of the 120 mostly cell-differentiation and proliferation related genes scientists believe to be a causative factor in the etiology of lung cancer. This is particularly interesting, because supplementation with larger amounts of the vitamin A precursor beta-carotene has been found to pose a serious health risk for smokers. With a passive smoke exposure equivalent to 80 nonfiltered commercial cigarettes the per day it is almost marvelous how effective the 10mg/kg bodyweight of all-trans retinoic acid were.

Figure 1: While all-trans-retinoic acid (left, bottom) appears to have potent anti-lung-cancer effects the β1-apocarotenoids our bodies produce from beta carotene could potentially negate these beneficial effects (see "Anti-Vitamin A Effects of Beta Carotene"); this would also explain why previous research has shown that beta-carotene supplements are potentially hazardous for for smokers (cf. Druesne-Pecollo. 2010)

I guess, the most studious among you will probably already know how the differing effects of vitamin A (real ATRA) and beta carotene come about, right? In my recent blogpost on the "Anti-Vitamin A Effects of Beta Carotene", I did actually provide a mechanistic explanation as the metabolic byproduct that arises from high dose beta carotene supplementation will block the retinoic acid receptor (similar to the way a SERM blocks the estrogen receptor) and thus inhibit the inhibitory effects of real vitamin A on the occurrence and progression of cancerous growth.

Image 2: Helicobacter pylori, ain't the reason you get lung cancer, but smoking will help him to prepare the breeding ground for gastric cancer.

Apropos lung cancer, a study by Koshiol et al. has recently refuted the claim that Helicobacter pylori (H. pylori) infections would increase the risk of lung cancer (Koshiol. 2013). Previous research from the German Center for Research of Ageing, on the other hand, found conclusive evidence that the combination of h. plyori and smoke increases the risk of gastric cancer by more than 600% (Brenner. 2002)! But don't worry, all-trans-retinoic acid can take care of that, as well. At least in the Petri dish, incubation of human gastric cancer cells with ATRA lead to immediate growth arrest (Zhang. 2005)... and did I mention it does the very same thing to pancreatic cancer, breast cancer and leukemia cells?

Implications: Regardless of whether you live with a chainsmoker, work in a bar or are stranded on a lonely island, where your campfire is the only source of smoke in your life, try to get your real vitamin A (=retinol) from fatty animal products and forget about beta carotene supplements (even if you brought some to your lonely island ;-). With fatty fish, a piece of liver every now and then, butter, eggs, etc. and large amounts of green leafy vegetables and a reasonable amount of whole fruits (no juices!) you are guaranteed not to fall short of any of these "vitamins A" (retinol and beta carotene) and the multitude of other potent carotenes that would be missing from your supplements anyway.

Type of fatty acids in cerebral fluid determine metabolic rate

Image 3: Assuming that the fatty acids you eat also float around in your brain peanut oil (1-2.5% C:24) is the worst edible oil for anyone who is concerned about his overnight energy expenditure.

A study that has just been published on PLos ONE provides astonishing insights into how long chain fatty acids (saturated fats) in your cerebral fluid could (we are dealing with observational human data from a metabolic ward study, here) slow down your fat loss or even make you gain weight by decreasing overnight energy expenditure. With correlations in the range of -0.6, lignoceric acid (C24:0, as in peanut oil) and Cerotic acid (C26:0; as in beeswax) are by far the worst offenders, as far as overnight energy expenditure are concerned; and though the design of the study did not allow for any conclusions on the underlying mechanisms, the fatty acid induced suppression of the nocturnal surge in growth hormone could be one potential and at least in my humble opinion not very far-fetched cause for this effect. Interestingly, things look completely different for the plasma levels of these fatty acids, which showed the exact opposite +0.6 correlation with 24h energy expenditure. Other noteworthy results were

• significant correlations of the mono-unsaturated fatty acids palmitoleic and oleic acid in the cerebrospinal fluid with higher rates of fatty acid oxidation (relative to carbs, not total) and 
• significant correlations of the omega-6 fatty acids linoleic (18:2n6), dihomo-g-linolenic acid (20:3n6) and arachidonic acid (20:4n6), the omega-3 fatty acids linolic acid and docosapentaenoic acid (DPA, C22:5n3) and the omega-9 fatty acid mead acid (C20:3n9) with better glucose clearance.

And no, the much-lauded fish-oil, i.e. the EPA and/or DHA content of the cerebrospinal fluid, had no significant effect on glucose tolerance. A result, by the way, which reminds me of another study I came across recently:  In their four day supplementation trial Miller et al. observed vast differences between the incorporation of EPA and DPA (docosapentaenoic acid, the one that did correlate - weaker than the omega-6s, though - with improved glucose tolerance) into plasma and red blood cell lipids subsequent to the oral provision of 8g/day of each to ten healthy women. Their observations and the respective alterations in EPA and DHA in the DPA supplementation group Miller and his colleagues concluded that DPA could serve as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans - exciting stuff and probably something you will read more about, here at the SuppVersity in the future.

Image 4: The data would support the use of MUFA and omega-6 laden olive and high MUFA macadamia oils, if we know how their consumption effects the fatty acid flux in our brains.

Implications: Due to our lack of knowledge about the ultimate determinants of cerebrospinal fluid fatty acid composition it is hard to say if these results do imply that you better focus on MUFAs in view of their beneficial effect on both glucose clearance and respiratory quotient - and still the usefulness of MUFA and omega-6 laden olive oils, which have time and again been shown to produce all sorts of favorable changes in glucose, fat and overall energy metabolism would support the notion that there is a direct or indirect downstream effect of higher intakes of the respective fats, their occurrence in our cerebrospinal fluid and their downstream metabolic effects.

Cooling trained muscles appears do decrease regeneration

Soon to be published in the Journal of Strength and Conditioning Research are the results of a randomized cross-over study into the effects 15 minutes of icing applied 0h, 3h, 24h, 48h and 72h after an intense eccentric arm workout with 6 sets of elbow extension performed at 85% maximum of the voluntary maximal load had on the subjective as well as measurable (inflammatory cytokines, creatine kinase (CK-MB), hemoglobin and oxygenation were assessed) regeneration of 11 young male college baseball players (Tseng. 2013).

Figure 2: Inflammatory cytokines, creatine kinase and visual analgue scale data on subjective perception of fatigue at different timepoints before and after the eccentric arm workout (data adaptedm from Treng. 2013)

As you can see from the data in figure 2 the icing did have a somewhat bizarre effect on the inflammatory and subjective indexes of muscular regeneration. While...

[...] significant change in the levels of IL-1β, IL-8, and IL-1 were observed following the muscle-damaging eccentric exercise in either the control or topical cooling conditions and no differences in these cytokines were found between the control and cooling trials throughout the 72 h observation period (data not shown in figure 2, Tseng. 2013).

The levels of the pro-anabolic cytokine IL-12 (Argile. 2001), TNF-α, and IL-6 were significantly lower 24h after the workout (see figure 2, left; p < 0.05). There were yet no significant differences at other time-points ant both the CK-MB, as well as the fatique score (figure 2, right) suggest that the overall regenerative capacity was compromised by the repeated cooling of the strained musculature.

Image 4: If you use a 41°C hot bath 48h before a workout to "pre-generate", you don't even need to ask yourself whether or not the results of the study at hand conclusively imply that icepacks are detrimental and their use after workouts has to be avoided at all costs.

Although I must admit that this is not a settled case for me, until we understand the unexpected dip in IL-12, TNF-α, and IL-6 after 24h and its relation to the obvious increase in muscle damage (CK) and corresponding fatigue levels, it would appear prudent not to make use of an icepack as your regenerative means of choice.

Instead, I would suggest you follow the example of the young lady on the left and take "pregenerative" measures by taking a 41°C hot bath 48h before a strenuous workout. As you will probably remember from my previous article on the Touchberry study (read full story based on Touchberry. 2013) this will not just keep the damage at bay, but may also help you on your quest to a more muscular physique. And if you want to do your immune system a favor, check out the on very short notice item about RNA + DNA precursor supplementation further down...

On Very Short Notice

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  Image 5: Adding ibuprofen on top of exercise will make your gut look like a riddle screen.

  Ibuprofen makes an exercise-induced leaky gut even leakier - The use of NSAIDs such as aspirin and ibuprofen has long been implicated in the etiology of all sorts of gastrointestinal problems ranging from benign gastroinstestinal distress, over gastrointestinal bleading, ulcers etc. to all sorts of cancers. Researchers from the Top Institute Food and Nutrition at the University of Maastricht in the Netherlands have now found that the way by which ibuprofen aggravates the exercise-induced small intestinal injury and induces an even more pronounced gut barrier dysfunction in healthy individuals than exercise alone, may not just contribute to the occurrence of the aforementioned pathologies, but also precipitate to systemic diseases. After all, it opens up the doors to pathogens and toxins, which would otherwise be blocked by an intact intestinal barrier (van Wijck. 2013).
  N-acetyl-L-cystein (NAC) a potent natural anti-inflammatory which has also  been shown to reduce exercise induced inflammation (see "NAC Improves Markers of Oxidative Stress Induced by High Intensity Exercise") and glutamine (in the dos Santos study a HED of "only" 3-5g/day), on the other hand, exert protective effects on the integrity of the intestinal barrier (Sun. 2002; dos Santos. 2010).
• Fish oil enema ameliorates colitis - When administered intra-rectally at a human equivalent dose of  ~13ml, fish oil effectively ameliorated the mucosal damage in experimentally induced ulcerative colitis in rat; flax oil and the corn oil control, on the other hand, did not prevent the increase in colonic weight / /length ratio and the associated histological changes 24h after Aisha Mohamed Dugani, Ahlam Elhelawi and Aisha Edrah had administered 1ml of 4% acetic acid to induce the colic (Mohamed Dugani. 2013). These results stand in line with general colon-protective effects of fish oil, observed in other studies and it's likely that they are a direct consequence of its non-negligible anti-inflammatory effect - which does not change my assessment that healthy physical culturists should not take more than max. 2g of supplemental fish oil per. The evidence supporting any beneficial effects on non-insulin-resistant, non-obese, non-hypertriglyceremic individuals is simply non-existent.

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  Image 6: No, this certainly does not look as if the conjugated linolic acid would work in horses as it does in mice ;-)

  Species specific effects of CLA: Horse don't lose weight, either - You will probably remember my recent post on the adipose tissue destroying effects of CLA (cf. "CLA Destroys Body Fat") in rodents, as well as my remarks that - if we discard potential underdosing as a contributing factor - it would appear that the beneficial effects of CLA we see in rodent studies is highly species specific. Now, Headley et al. have published the results of a study that investigated the effects of 0.05% CLA enriched chow on horses. Similar to what we see in humans, the conjugated linoleic acid had no effect on the body composition of the animals. Interestingly though, the mixture of three CLA isomers used in the study (cis-9, trans-11 + trans-10, cis-12 + and trans-9, trans-11; usually we have only the latter two in significant amounts) led to a statistically significant reduction of the potentially pro-inflammatory arachidonic acid in the blood of the horses. This spiked the interest of Headley et al. as it could turn out that this would render CLA (this specific isomer mix, I should say) as an agent that could have beneficial effects on the progression of joint disease, which is - in parts - driven by C20:4 (chemical name for arachidonic acid).
• Towards a better understanding of why fructose is making us fat - Using in-vitro studies and a genetically engineered Glut5 -/- mouse model (these mice lack the glut-5 receptor which is responsible for the uptake of fructose), Li Du and Anthony P. Heaney were able to show that the preferential expression of Glut5 in developing adipocytes and the corresponding adipogenic (=promoting the creating of new fat cells) effects of fructose could well explain why fructose, which can no longer be taken up by mature fat cells, has been shown time and again to be way more fattening than its pro-insulinogenic cousin glucose (Du. 2013). Put simply, you could say: Increased serum levels of fructose require a) the conversion of fructose to triglycerides of glucose in the liver or b) the proliferation of adipose tissue so that the developing new fat cells can take the superfluous fructose up. If you consume too much of so that your liver is already working overtime, it is no wonder that your healthy high-fructose corn-syrup fat-free breakfast cereals are making you fatter and fatter. 

• 

  Figure 3: Effects of incremental treadmill running on selected markers of immune activity before and after 2 weeks of sublingual treadmill running in 38 healthy young men nucleotid supplementation (Ostojic. 2013)

  Supplement with RNA and DNA building blocks protects from immune-suppressive effects of exercise - The effects Sergej M Ostojic and Milos Obrenovic observed in response to a 14-day sublingual nucleotide supplementation regimen were basically what common wisdom tells you, you should see as a result of glutamine supplementation (Ostojic. 2013): The RNA and DNA precursors did not just ameliorated the dreaded immune-suppressive effects of a standardized cardio workout on a treadmill, they effectively boosted natural killer cells count and cytotoxic activity as well as salivary immunoglobulins and lactoferrin (cf. figure 3); so profoundly, though, that I am not 100% sure this is a good thing - at least not for people with auto-immune issues.
• Don't stress yourself if you want to recover as fast as possible! That's the take home message of a recently published study by two researchers from the Nothern Illiniois University and the University of Texas at Austin, who correlated measures of perceived psychological stress with physical data on exercise recovery and found a surprisingly linear relationship between perceived stress, on the one hand, and phyical recovery as measured by maximal isometric force, on the other hand, in 31 undergraduate resistance training students (Stults-Kolehmainen. 2013). So, mark my words: Don't overstress about making everything right (this includes having the optimal workout and nutrition plan and thinking about whether or not you should add in another 0.5g BCAA pre-workout or not), if you don't want to sabotage your training success.

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