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marylin monroe
Showing posts with label arachidonic acid. Show all posts
Showing posts with label arachidonic acid. Show all posts

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. 2012) 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. 2012) -- 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. 2012)
    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. 2012)
    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. 2012b) 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. 2012a & 2012b)
    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. 2012b)  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. 2012) 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. 2012)
    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. 2012): 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. 2012) 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. 2012) -- 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. 2012 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. 2012a 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. 2012b; 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 2012, 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. 2012; 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 2012; 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. 2012; 9(Suppl 1):P29

    Caffeine Protects Brain Function Against Stress & SAD Diet; Coffee Withdrawal, Anxiety & More; Giardia, Messy Subtenant W/ Gusto For Arginine; Vit B6 & n6:n3 PUFA Ratio

    19 Billion Euro that's the estimated 2011 financial burden due to lung cancer, alone, here in Europe and the On Short Notice figure of the week (information based on ESMO2012 press release)
    Those of you who are also following the SuppVersity facebook news, will probably recognize the figure on the right: 16,000,000,000€ or $24,419,000,000, that's the estimated economical burden due to lung cancer, alone, here in Europe (cf. "Who cares if people are dying as long as the economy is thriving?"). An enormous financial loss, and still not the reason that this is my figure of the week. Rather than the financial damage, itself, it is the tragic fact that only the latter, yet not the fate of the patients and their families, would make a valid argument, when policy makers were debating a long overdue, total and all-encompassing public smoking ban... but now for a couple of more sciency, yet not less intriguing news from the past week.



    Problems thinking straight? Guess what: 3-4 cups of coffee could help :-) According to a soon-to-be-published paper by scientists from the Jordan University of Science and Technology in Irbid, Jordan, the ingestion of the human equivalent of approximately 3.8mg caffeine per kg body weight or 3-4 cups of coffee per day, can inhibit both, the stress, related as well as diet induced (we are talking of the "typical" Western diet (WD), that's both high in carbohydrates and fat) cognitive impairments (Alzoubi. 2012)... well, at least in the researchers 3-months rodent study it worked like a charm
    • learning trial: animals in the caffeine/stress, caffeine/WD, and caffeine/stress/WD groups made fewer errors, than non-supplemented stressed or WD animals; overall their performance was comparable to those of the control
    • memory tests: treatment reduced the number of error and restored short-term memory and long-term memory during chronic stress and/or WD (P < 0.05) to normal levels
    With respect to the underlying mechanisms the scientists speculate that caffeine may "act mainly by inhibiting adenosine receptors" (Alroubi. 2012), which has in turn been shown to to inhibit long term potentiation (LTP) in rat hippocampal slices and disrupt the process of learning and memory at the synaptic level by blocking release of glutamate (de Mendonca. 1994).

    Additionally, caffeine has also been shown to increases the expression of hippocampal brain-derived neurotrophic factor (BDNF) and its receptor, which is impaired in response to chronic stress and a hypercaloric Western diet (Aleisa. 2006; Molteni. 2004) and leads to deteriorations in cognitive performance. In the long run those effects could also contribute to the anti-dementia and anti-Parkinson's effects, I mentioned in the recent SuppVersity post on the insulin sensitizing effects of coffee.



    Figure 1: While the Hedonic tone and alertness reduced to baseline on day 5 of caffeine withdrawal, the habitual caffeine consumers had >15% higher anxiety scores on day 7 after giving up on their daily dose of methylxanthine (data calculated based on Smith. 2012).
    Don't worry, caffeine will also work for humans. And what's best, upon short-term withdrawl (8 days) your cognitive performance is not going to suck - at least not as much as when you are stressed or living on pizza and French fries, only. All that and a couple of interesting other results have been published ahead of print in the online version of the Journal of Pharmacology (Smith. 2012).

    To probe the effects of acute caffeine ingestion on cognitive performance and the influence of previous caffeine consumption and withdrawal, Andrew P Smith, Gary Christopher and David Sutherland recruited 70 volunteers (25 male, 45 female; mean age 22.8 years). The 35 consumers (>100mg caffeine /day, mean 300mg; range 110–600 mg) were put on withdrawal and tested on day 2, alone and without caffeine, and day 8 together with the non-consumers in a double-blind placebo-controlled fashion. During the caffeine challenge, the cognitive performance was tested twice, once before and once 30min after the provision of the caffeinated beverages.

    Anxious, but smart: Caffeine gives you the edge

    The results of the trial clearly indicate that the ingestion of 2 mg/kg of caffeine, which were served in decaffeinated coffee or tea 30min before the testing procedures, were associated with faster simple reaction times, fewer long responses, greater detection of targets in the cognitive vigilance task, and faster encoding of new information.
    "The results confirmed previous findings, with ingestion of caffeine being associated with a faster simple reaction time, fewer long responses, more targets detected and faster encoding of new information. There were no main effects of consumer status, nor were there any significant interactions between caffeine and consumer status." (Smith. 2012)
    Notwithstanding, I believe that many of you will probably be more interested in the effects of caffeine withdrawal on overall withdrawal symptoms (figure 1, top), as well as the alertness, hedonic tone and anxiety (figure 1, bottom) and the cognitive performance on day 2 of the withdrawal period (figure 2, left), than in any of the well-established performance cognitive performance boost, right?
    Figure 2: Performance on day 2 of withdrawal phase (w/out caffeine) and on day 8 before (w/out caffeine) and after (w/ caffeine)the ingestion of decaffeinated tea or coffee with 2mg/kg caffeine in it (data based on Smith. 2012)
    As you can see on the left-hand side of figure 2 there was a minimal performance decline on day 2 of the withdrawal phase, but the latter was statistically not significant and all measured markers of cognitive function had returned to normal on day 8 (remember longer response times = worse performance!), when the resumption or first time provision of caffeine spiked the reaction times and lowered the mistakes in all tests, irrespective of whether the subjects were former habitual consumers on withdrawal, or not.

    Outside of controlled experiments "real" coffee and tea do at least as well

    Since a large cup of coffee contains about the same amount of caffeine the scientists simply added to decaffeinated beverages, to ensure that the drinks could not be distinguished (by their smell for example), you can simply stick to your regular coffee and if you want to enjoy similar benefits. And to be honest, in view of the plethora of benefits of chronic low dose coffee consumption, I would not even think for a second about whether or not you may be missing out on the occasional boost, when you are not "going on withdrawal" from time to time...



    Figure 3: W/out arginine (Arg-) intestinal epithelial cells can't proliferate (graph based on Stadelmann. 2012)
    Giardia eats away your guts arginine supply and makes itself at home within an increasingly morbid digestive tract! As a group of scientists from Sweden and Argentina reports in their latest paper, the protozoan parasite, Giardia intestinalis, feasts on the arginine your gut cells need to proliferate (Stadelmann. 2012). This will lead to reduced polyamine levels and upregulated cell cycle inhibitory genes, which will eventually disrupt the the cell cycle of the intestinal epithelial cells. The reduced intestinal epithelial cell proliferation, on the other hand, allows the gut pathogen to thrive and will, in the long run, disrupt the intestinal tissue homeostasis and thus initiate the decay of the intestinal epithelium  - a central feature of so many of the wide-spread gut pathologies.

    Provision of additional arginine + citrulline can help ... in the short run

    Now, the good news about all that is that the in-vitro data in figure 3 clearly suggests and anecdotal, as well as the effective therapy of diarrhea patients with arginine/citrulline actually confirm that the provision of supplemental arginine (or citrulline) constitutes a cheap and readily available way to ameliorate the decay, until the bugs have been eradicated by antimicrobial drugs.

    A pros pos, antimocrobial drugs, with regard to latter, Noa Tejman-Yarden and Lars Eckmann write in a recent review of the latest drug innovations, that despite the fact that metronidazole and other antimicrobials are usually effective, "treatment failures are common and antimicrobia resistance occurs" (Tejman-Yarden. 2011), so that it would appear as if complex derivatives of 5-nitroimidazole and benzimidazole, which form the core structure of the most widely used antigiardial drugs, will replace them in the short-run. At least for so long, until several new classes of antigiardial drug candidates that have already been identity by high-throughput screening of large compound libraries, will eventually hit the market (Tejman.Yarden. 2011)




    More about vitamin B6: Helps with neurotransmitters synthesis; is involved in nerve function and necessary for normal brain development & function; influences mood, and melatonin production; effects circadian clock; is needed for B12 absorption and thus red blood cell production
    When low: "Pins and needles" in extremities, mental disorders, seborrheic dermatitis, estrogenic PMS, dizziness, irritability, kidney stones, abnormal EEG, anemia, convulsions, edema (water retention), hypothyroidism, migraine-headaches, glossitis, lymphopenia
    When high: Depression, suicidal tendencies, severe fatigue, mood swings, low blood sugar, migraine-headaches, heart palpitations, thyroid abnormalities (hyper- in the short, hypo in the long term), numbness in hands and/or feet, spinal / nerve degeneration, muscle spasms / cramps, osteoporosis, arthritis, higher blood pressure (short-term suppl.), lower blood pressure (long-term suppl.), mineral imbalances (high phosphor & magnesium vs. low sodium & calcium), restlessness, insomnia, vivid dreams, decreased estrogen & prolactin, depressive PMS.
    RDA (adults): 1.3 mg*
    *higher for pregnant women & >50y
    Upper tolerable limit: 30-100mg*
    *depending on the source of information
    Food sources: chicken, turkey, tuna, salmon, shrimp, beef liver, milk, cheese, lentils, beans, spinach, carrots, brown rice, bran, sunflower seeds, wheat germ, and whole-grain flour
    n6:n3 ratio does not depend on dietary intake alone: A marginal deficiency in vitamin B6 will skew your serum PUFA levels towards the N6-side That's the long and short of the results of a study that's going to be published in the October issue of the Journal of Nutrition.

    Mei Zhao and her colleagues analyzed the fatty acid profiles in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC) of healthy men and women who had been fed a low-vitamin B-6 (pyridoxine) diet for 28 days and observed that contrary to the plasma HDL and LDL cholesterol concentrations, the amount of free fatty acids (FFA) in the blood and the erythrocyte and PBMC membrane fatty acid compositions, neither of which showed any statistically significant changes, the amount of all long-chain polyunsaturated fatty acids, i.e. arachidonic acid (n6) and EPA and DHA (n3) decreased from 548 ± 96 to 490 ± 94 μmol/L, 37 ± 13 to 32 ± 13 μmol/L, and 121 ± 28 to 109 ± 28 μmol/L, respectively.

    The subsequent 8% increase in the total n6:n3 PUFA ratio from 15.4 to 16.6 is not alarming, but if this trend would continue linearly, it would certainly become problematic, in the long run. Moreover, the decrease in both n6 and n3 long-chain PUFAs (of which people tend to forget that the "inflammatory" arachidonic acid is as vitally important as its "anti-inflammatory" omega-3 counterparts) could provide an alternative / complementary mechanistic explanation for the increased cardiovascular disease risk that has been associated with vitamin B-6 deficiency.

    In view of the fact that the RDA is not exactly high and can easily be achieved from dietary sources, along (as long as you follow a diversified whole foods diet), and considering the fact that high levels of B6 have been associated with more negative side-effects than B6 deficiency (see infobox on the right; please note that I collected the information on a couple of trustworthy websites on RDAs & co and did not verify the research on each of them!), I would however caution against the typical Western "more helps more" supplementation mentality.





    Figure 4: Easy come, easy go - the mass you gain and the fat you lose by doing nothing than simply injecting testosterone is lost / regained within 6 months after discontinuation of the "testosterone therapy" (Forbes. 1992); read more about the role of testosterone in skeletal muscle hypertrophy in the Intermittent Thoughts on Building Muscle
    In view of the fact that (a) today's short news items are pretty long(ish) and you still got a couple of interesting facebook news to check out, such as...
    ... and a plethora of additional gems from the realms of health, exercise, nutrition & supplementation, I will call it a day for today and save the exercise and a couple of other exciting On Short Notice items for later next week.


    References:
    • Aleisa AM, Alzoubi KH, Gerges NZ, Alkadhi KA. Chronic psychosocial stress-induced impairment of hippocampal LTP: possible role of BDNF. Neurobiology of Disease 2006;22:453–62. 
    • Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KA. Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet. Behav Brain Res. 2012 Sep 20.
    • ESMO. Press releases related to the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.
    • Forbes GB, Porta CR, Herr BE, Griggs RC. Sequence of changes in body composition induced by testosterone and reversal of changes after drug is stopped. JAMA. 1992 Jan 15;267(3):397-9.
    • de Mendonca A, Ribeiro JA. Endogenous adenosine modulates long-term potentiation in the hippocampus. Neuroscience 1994;62:385–90.
    • Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gomez-Pinilla F. Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor. Neuroscience 2004;123:429–40.
    • Smith AP, Christopher G, Sutherland D. Acute effects of caffeine on attention: a comparison of non-consumers and withdrawn consumers. J Psychopharmacol. 2012 Sep 19.
    • Stadelmann B, Merino MC, Persson L, Svaerd SG. Arginine Consumption by the Intestinal Parasite Giardia intestinalis Reduces Proliferation of Intestinal Epithelial Cells. PLoS ONE. 2012; 7(9): e45325. 
    • Tejman-Yarden N, Eckmann L. New approaches to the treatment of giardiasis. Curr Opin Infect Dis. 2011 Oct;24(5):451-6.

    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.

    Restore & Maintain Insulin Sensitivity - Basics: Turn Your Lifestyle Upside Down With These 5 "No-Quick-Fix" Tips

    It is hard and it takes time, but as long as it's "only" insulin resistance and not full-blown diabetes (=pancreatic failure) most people can get rid of it by turning their lives upside down.
    I am sure people are going to misunderstand this, but in the end, insulin resistance was, is and will always be a consequence of "obesity". Maybe not in the way it is currently understood with the BMI determining whether you are "normal" or "obese", but certainly if you define being obese as being fat and storing the most part of the fat in the visceral adipose tissue and the liver.

    Thus our definition of what I would like to call "metabolically relevant adiposity" instead of "obesity" can apply to lean and "obese" people alike. In fact, the number of people with a "normal body weight" and insulin resistance is ever increasing. So, if you don't want to be one of them, you better keep the following five DOs and avoid the corresponding "DON'Ts", which would be sitting or lying around all day, eating and drinking sugar-sweetened foods and beverages, consuming alcohol (and other hepatoxic substances), smoking cigarettes, staying up late, eating 24/7, missing your daily time-outs and abusing stimulants.
    Details on the optional use supplements & medications will follow next Sunday. What I can already tell you, though, is that can get rid of insulin resistance without a single supplement or pharmacological agent, but you will never get off the diabesity track, if you are unwilling (don't you ever tell me you are "unable") to change the way you eat and increase your daily activity levels.

    And yes, lifestyle modification is all it takes for most of us to regain insulin sensitivity and rid ourselves of type II diabetes (in the early stages): With 50% of the subjects being able to normalize their blood glucose levels and more than 50% of the type 2 diabetics in the study being in remission on the follow up, he Malmö study was the first, but is not the only the large scale intervention study that demonstrated the potent anti-diabesity effects of diet and exercise (Eriksson. 1991).
    I. Work out anaerobically, aerobically and frequently

    Workout evolution: It goes without saying that I don't expect you to start working out 5x per week "cold turkey", i.e. if you have been sitting around 364 out of 365 days of the year for the most part of your previous life (I don't have to repeat that this is over, now, right?). On the other hand, I would be lying if I told you that you can actually make measurable progress without at least 3 workouts per week. I would thus suggest you start with a 2 + 1 strategy using 2 full body workouts and one light intensity cardio training, after a month you add another cardio session and after 3 month you will add in the additional strength training session. After 6 months you switch to a split routine and increase the intensity on your cardio sessions by 15% - this should not feel more intense now that your fitness has improved than the original regimen you've taken up 180days before.
    There is nothing that helps your body clean up the mess like working out. Researchers from the University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona have just published a paper on the differential effects of strength and aerobic training on the liver fat content in type 2 diabetic subjects with NAFLD. The results were pretty amazing.

    After only 4 months in the course of which the subjects ate according to the (imho not exactly optimal dietary recommendations for type II diabetics; i.e. low fat) and 3 workouts per week, both the subjects in the 3x9 exercise in a circuit training fashion and their peers in the 60min aerobics @ 60-65% of the max. heart rate had lost 32.8% and 25.9% liver fat.
    "Additionally, hepatic steatosis (defined as hepatic fat content>5.56%) disappeared in about one-quarter of the patients in each intervention group (23.1% in the AER group and 23.5% in the RES group." (Bacchi. 2013)
    While there is no study that measured the effects of training fasted on the liver directly, I guess you can take it for granted that esp. the group doing the aerobics could have improved their results even further, if they had performed their 60min of cardio on empty.

    Bottom line: Get active or stay active. Combine resistance and aerobic training. Get serious and start working your way up to 5 workouts per week with 2x aerobic (steady state walking on an incline treadmill or taking a fast walk for 45min) and 3x resistance training sessions (either a circuit training or a pull, push, legs, 3-way split; don't train to failure in more than one set per exercise, keep the reps in the 8-10 range, increase the weights appropriately, do max. 18 sets per workout, in & out of the gym in <30min) to get rid of your insulin resistance and at least 3 workouts (2x weights, 1x LISS) if you just want to keep your insulin sensitivity is already high and you want it to stay just there.

    II. Minimize your sugar intake, control your carb intake

    In case you wonder where the 120g come from and if this is just some random number, I suggest you go back to a previous SuppVersity post, namely "Carbohydrate Shortage in Paleo Land: New Data for A Scientific Outlook at the Low-to-No Carb Paleo Confusion. Will More Than 125g of Carbs Make You Fat?", you may also want to reread my interview w/ Sean Casey at CasePerformance.com
    Sugar, irrespective of whether its plain table sugar or HFCS is a no-go from now. The same goes for all products that contain significant amounts of it. And no, you are not going to cut back slowly on your Coke, you know that you've failed miserably before and you will fail again. You simply won't buy and drink any sugar containing beverages (including "healthy" juices which have only recently been associated with an almost 25% increased risk of developing type II diabetes) and foods.

    At the same time, you will reduce your carbohydrate intake to 120g per day with a 40g limit on a per meal basis. It should not be necessary and may even be detrimental to go further down, because you won't ever learn how to walk without a crutch if you sit in a wheelchair - or to leave the metaphors behind: Unless you intend to stay insulin resistant and metabolically unflexible for the rest of your life, you better not go "no carb", as this will effectively require a high degree of (physiological) insulin resistance to work (for the morbidly obese it may yet be necessary to take the ketogenic route).

    Moreover, the "gray area" between 120g and no-carbs sets you up to hypoglycemic episodes as your body will not effectively switch into ketosis, which would be necessary to supply a steady amount of energy. This problem will become even more pronounced, when you try to make up for the lack of carbs by consuming exorbitant amounts of protein.

    Unless you are "skinny fat" (normal or low BMI + insulin resistant) you will use the reduction in carb intake to generate a -15% to -20% caloric deficit to shed a couple of pounds of fat weight - and no, this is NOT going to happen without a caloric deficit.

    Bottom line: 120-150g is an amount of carbs you should aim for as an intermediate goal. With <50g of carbs per serving you should be able to handle that without major blood sugar excursions, as long as you stick to your workout regimen and totally cut out processed foods with simple sugars. Also, fructose from whole fruit is not your enemy! You just have to make sure you account for it in your daily carb allowance. The latter is not the case for the minimal amount of carbs in green leafy veggies and co (broccoli, calliflour, zuccini, asparagus etc. you can safely fill yourself up on those)

    III. Limit your alcohol intake, quit smoking and avoid medications

    Contrary to its name, which is "non-alcoholic fatty liver disease", alcohol, does still play a major role in the etiology of NAFLD. It may not be the sole reason, but the way it inhibits the normal function of your liver makes it more susceptible to the junk-food assaults it's exposed to on an almost daily basis. The same goes for all medications / "supplements" with hepatoxic effects.

    Compromised liver health as in beginning or full-blown (N-)AFLD is a totally underestimated risk factor for gyneco- & lipomastia as it hampers the not only the glucose, but also the hormone metabolism in the liver (learn more)
    Cigarettes on the other hand may not be directly damaging your live, but they stimulate the central nervous system, promote gluconeogenesis and impair it's shut-down, when your blood sugar is already high, so that your liver will actively and acutely contribute to the deterioration in blood sugar metabolism. At the same time the increased efflux of free fatty acids (FFA) from the adipose tissue to the liver increases your risk of developing NAFLD.

    Moreover, nicotine does also increase the chronic mammalian target of rapamycin (mTOR)/p70S6 K activity and insulin receptor substrate-1 (IRS-1) Ser636 phosphorylation and will thus directly promote skeletal muscle insulin resistance (Bajaj. 2012).

    Bottom line: While the chronic ingestion of more than 1 glass of wine per day is going to give you alcoholic liver disease, regular weekend binges precipitate and accelerate the development of NAFLD and insulin resistance. Cigarettes will compromise your insulin sensitivity in multiple ways and the use of medication, let alone performance enhancing drugs with detrimental side effects on the liver will exponentially increase the negative impact of any dietary glitch on your insulin sensitivity.

    IV. Sleep, de-stress and control your stimulant intake

    Please remember: Sympathetic overtraining from heavy lifting can cause sleeplesness while para-sympathetic overtraining from training too much (you can easily make the transition from sympathetic to parasympathetic overtraining), will leave you exhausted 24/7 - the 5x/week scheme above is only sustainable if you stick to the given volume and intensity limits and light intensity steady state cardio training (if you want on empty early in the morning). The latter is a better complement to restistance training than HIIT for improving insulin resistance because there is less overlap between the metabolic pathways they target).
    Not getting enough sleep, alone will hamper you ability to handle glucose. This is mostly due to changes in the hormonal profile with chronically elevated cortisol levels esp. in the evening, a lack of nightly growth hormone stimulation and a desynchronization of the central (brain) and peripheral (liver, muscle, other organs) clock.
    Figure 1: After 6 nights with only 4h of sleep (left) your glucose insulin response to breakfast deteriorates compared to 6 nights with 12h spend in bed (not necessarily 12h sleeping; Spiegel. 1999)
    Even if you are sleeping enough constant psychological stress will have very similar effects on your insulin sensitivity.

    The latter is also true for the use of stimulants. It's scary to see how many of us depend on them to even make it through the day. Aside from circadian shifts, they will have the same detrimental effects on the FFA metabolism and gluconeogensis as cigarette smoking (see discussion under item III).

    Bottom line: Plan your sleep and time-outs across the day as rigorously as your workout & nutrition. Spend 8h in bet every night (if that does not help try 1-10mg of melatonin; learn more). Close the curtains and use ear-plugs if that helps you sleep. Schedule at least 15 minutes of idleness every 3h. That's about as much time as it takes to brew and drink a cup of tea. The emphasis here is on "a" (=a single) cup of tea. If you feel too tired to make it through the day without >400mg of caffeine, this is a clear cut sign you got to revise your sleep & destress routine.

    V. Fast, get enough protein and watch your omega-6 intake

    US childhood obesity map. Go back to the "Insulin Resitance Saga" to learn about the roots diebesity in the kindergarten.
    I am aware that the general advice is different, but if you eat every 1-2 hours even the blood glucose levels of a normal person will hardly ever go back to those levels, where you want them for AMPK to go up and initiate the "decluttering" process in your liver and the rest of your body (learn more).

    Also try and to get ~2x the RDA, i.e. 1.6g of protein per kg of body weight from food (learn why) and spread your protein intake across your meals in a way that ensures that you'll get at least 30g or quality protein per meal (find out why this is important). Consider using a protein shake after your resistance training sessions.

    If possible include fatty fish in your diet on one, better two days of the week and keep an eye on your overall omega-6 intake. Try to reduce it to achieve a 5:1 omega-6 to omega-3 ratio (or lower; learn why). If you cannot force yourself to eat fish, consume 1-2g of fish oil in capsules every other day.

    Too much of a good thing? Micrograph of non-alcoholic fatty liver disease, caused by the same kind of lipid accumulations M-Shirazi et al. observed in rats after receiving high dose fish oil supplements in a 2011 study (learn more)
    Don't discard the value of ALA (=short chain omega-3 fatty acids) and don't fool yourself to believe that saturated fats were totally benign. Increased levels of palmitic acid in the hypothalamus and skeletal muscle, for example, are mechanistically linked to local insulin resistance (Benoit. 2009; Hirabara. 2010). Everything in moderation!

    In this context it is also worth mentioning that you do not want to totally eliminate omega-6 fatty acids from your diet. A 2012 study by Sawada et al., for example, showed that the allegedly bad arachidonic acid (ARA, the end-product of the enzymatic conversion of short-chain omega-6 fatty acids) is a 75x more potent activator of skeletal muscle glucose uptake than oleic acid and on par with it's omega-3 cousin DHA (Sawada. 2012).

    Bottom line: Don't eat 2h before bed, and / or skip breakfast to extend your daily fasting period to at least 10h, but no more than 16h (you need that 8h window to fit in 2-3 meals). Get enough protein in your diet, but make sure you are not living off protein alone. Try to normalize your omega-6:omega:3 ratio. Strive for an 5:1 ratio of n-6:n-3 or less. Don't be fooled by the "saturated fat is not the problem"-lie and keep in mind that palmitic acid, not arachidonic acid is the bad guy, when it comes to skeletal muscle insulin resistance (things may look different when we are talking about endothelial inflammation, but this guide is about the remission of insulin resistance).
    Dont forget to come back next week for Part II of this two part series.

    References:
    • Bajaj M. Nicotine and insulin resistance: when the smoke clears. Diabetes. 2012 Dec; 61(12):3078-80. 
    • Benoit SC, Kemp CJ, Elias CF, Abplanalp W, Herman JP, Migrenne S, Lefevre AL, Cruciani-Guglielmacci C, Magnan C, Yu F, Niswender K, Irani BG, Holland WL, Clegg DJ. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents. J Clin Invest. 2009 Sep;119(9):2577-89.
    • Eriksson KF, Lindgärde F. Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise. The 6-year Malmö feasibility study. Diabetologia. 1991 Dec;34(12):891-8
    • Hirabara SM, Curi R, Maechler P. Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells. J Cell Physiol. 2010 Jan;222(1):187-94.
    • Sawada K, Kawabata K, Yamashita T, Kawasaki K, Yamamoto N, Ashida H. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells. Lipids Health Dis. 2012 Mar 12;11:36. 
    • M-Shirazi M, Taleban FA, Abadi AR, Sabetkasaei M. Fish oil increases atherosclerosis and hepatic steatosis, although decreases serum cholesterol in Wistar rat. J Res Med Sci. 2011 May;16(5):583-90. PubMed PMID: 22091279; PubMed Central PMCID: PMC3214368.
    • Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999 Oct 23;354(9188):1435-9.

    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. 2012). 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. 2012).
    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. 2012)
    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. 2012).
    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. 2012) 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

    • 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. 2012).
      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. 2012). 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.
    • 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. 2012). 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. 2012)
      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. 2012): 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. 2012). 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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