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

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

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

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

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

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

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

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

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

A Diet High in Dietary Antioxidant Keeps you Lean & Healthy

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

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

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

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

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

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

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

  On Very Short Notice

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

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

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

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

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

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

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

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

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

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

References:

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