The Female(?) Athlete Triad - Part III/III: Road to Recovery! Step #2 = Accept There is No Magic Macronutrient Ratio

No need to raid another tomb, Lara, the quest for the one and only ideal macronutrient composition that will yield optimal results for the rest of your life ends here (img courtesy of Paramount)!

I am not planning to bore you with a longish summary of the previous installment(s) of this series, here. Still, I don't want to head on to the 2nd step of the "Road to Recovery", which is going to deal with the quest for the "optimal" macronutrient ratio, without a brief reminder of the central role of nutrient availability in both the etiology, as well as the recovery from the athlete triad - or, as Dr. Zanker from the Carnegie Research Institute at the Leeds Metropolitan University in the United Kingdom puts it, the simple fact that the "exercise associated reproductive dysfunction in women is attributable to deficits of readily available energy" (Zanker. 2006)

In a couple of more general remarks some of you have recently (not without good reason, by the way) criticized my excessive and in parts random use of mark-ups like bold print or underlining. In the introductory paragraph to today's post the word "readily" is however so important that the underlining is obligatory.

Your hypothalamus does not like to wait, therefore "readily" is the keyword, here!

It is after all the lack of appropriate readily available energy, primarily in the form of circulating glucose, liver glycogen, and adipose tissue triacylglycerol that precedes the low plasma insulin concentration and reductions in total body fat content and corresponding disturbance of leptin secretion, ghrelin, cortisol, thyroid and of course luteinizing hormone (see data in figure 1; the absolute levels from the healthy group may also serve as a reference to compare your own labwork to; mind the units!).

Figure 1: Hormonal and glucose metabolism (* indicates 24h values) of women with functional hypothalamic amenorrhea (not necessarily exercise induced) expressed relative to values in eumenorrheic control; values above the bars indicate the total values of the respective markers in healthy controls and may provide you with some orientation, when you are looking at your own bloodwork (data based on Loughlin. 1998)

In order to avoid / counter the reproductive and associated problems and break out of the vicious circle of the athlete's triad, Zanker proposes the following three steps (based on Zanker. 2006; yet with a couple of additions from my side): 

• Avoid abrupt and rapid weight loss and maintain an “adequate” body fat content, which may be individually specific, but coincides with regular reproductive function.
• Consume adequate amounts of energy to fuel your increased metabolic demands; never go below your resting energy expenditure, regardless of whether you  want to or even have to lose weight.
• Make sure you get an adequate amount of carbohydrates either on a continuous (low GI carbs with every meal) or in a cyclic manner as part of a low(er)* carbohydrate diet with a baseline intake of 90-120g/day and additional carbs after every workout.
  *compared to the RDA of ~60% carbs

"Carbohydrates? But aren't those just making you fat?" With this very question that's now probably on the mind of one or two (or three ;-) of you, we did eventually arrive at the topic of this episode of the Athlete's Triad Series:

Is there a ideal macronutrient ratio that will prevent the onset
and help you get rid of the athlete's triad?

To be honest, I don't know the answer to this question... and although I had almost typed the word "yet" win the place where you now see the "..." , I must admit that I am not even sure if there actually is a definitive answer to this question. What I do have to offer, though, is a couple of things to keep in mind, when it comes to the macronutrient make-up of your diet.

1. There is no such thing as a "bad" nutrient. There are about as many good arguments to vilify the overconsumption of protein, as there are arguments against the usual scapegoats, carbohydrates and fats.
2. Glucose and saturated fats can be essential, too. Just because your body can produce carbs and saturated fats on its own, this does not mean that you do not have to, let alone should not eat them.
3. The optimal macronutrient ratio will change over time - just like and in response to the way your physique, conditioning, lifestyle, training and general stress levels  will be changing. This implies that diet X, which may have worked magically for you, when you got rid of slabs of body fat is now that you are finally in the "normal range", let alone already so lean that your body's alarm bells are constantly ringing, hampering your progress.

And even if the previous comments on the importance of readily available energy and glycogen repletion would suggest that carbohydrates should make up the lion's share of the diet of any athlete trying to recover from the triad (or not to fall victim to it), an extreme high carbohydrate alone is neither guaranteed to solve the problem nor is it a sustainable way of eating you could stick to once you've "carbed" yourself out of the dark hole you have been digging over the past months.

Readily available energy? Does that mean I have to eat sugar all day?

Figure 2: Cortisol (left) and testosterone (right) levels in healthy men after 10 days on high protein vs. high carbohydrate diets (based on Anderson. 1987). Tegelman et al. report similar results from Swedish elite male Ice Hockey players after a reduction of fat and an increase in carbs (Tegelman. 2007)

On the one hand, we've known for over two decades that a high carbohydrate diet based on bread, vegetables, fruit, juices, pastry, and candy having a protein / carb / fat ratio of 10% / 70% / 20% will result in lower cortisol and higher testosterone levels (in men) than a high protein diet with a protein / carb / fat ratio of 44% / 35% / 21% that's based on lots of meat, fish, poultry, egg whites, and a liquid dietary supplement protein supplement (Anderson. 1987; see figure 2). On the other hand, a closer analysis of the data I compiled based on the tabular overview of pertinent studies on amenorrheic from the review by Manore (see figure 3 in the last installment) suggests that real.world advantage of carbohydrates depends on the deepness of the whole you already dug (the deeper the more advantageous) and your willingness / ability to cover or even surpass your daily energy requirements (the more you eat on a daily basis and in at least three square meals spread equally across the day, the less you will depend on the readily available energy from carbs).

Against that background, the high carbohydrate intake (62% of total energy from carbohydrates; nutrient ratio in grams 16% protein, 71% carbs, 14% fats) was probably necessary for the women in the eumenorrheic group with an energy intake of slightly less than 30g/kg body weight (figure 3, R5).

Figure 3: Macronutrient compositions (in kcal!) of amenorrheic and eumenorrheic women from 15 different studies (based on an overview in Manore. 2002)

For the eumenorrheic female athletes who were at, or way above the average mean energy intake of 35g/kg body weight, the "high" carbohydrate intake of 265g/day probably wasn't detrimental. On the other hand, it appears questionable, whether an increase in protein intake from 1.2g protein per kg of body weight to 1.5-2.0g/kg and a corresponding protein to carbohydrate ratio of 25% / 62% would not have been more facilitative to their goals (specifically if those include strength training). The same goes for both, the replacement of yet another part of the carbohydrate ration with an isocaloric amount of fats and the overall role of fats in the etiology of and the recovery from the athlete's triad.

The fat-phobia still loomed large, when the majority of studies was conducted

Part of the problem of reconciling theoretical considerations, such as the "availability advantage" of carbohydrates and the scarce and almost exclusively observational data based on which I compiled the overview in figure 3 of this, as well as the last installment of this series, is that eating patterns of both the eumenorrheic, as well as the amennorheic athletes was geared towards the dietary paradigm of the day. With "the day" being the late 1980s and 1990s, i.e. those years in which the fat-phobia literally climaxed, it should be obvious that the baseline diet was low in fat and high in carbs.

Against that background it should also be clear that anyone trying to "cut calories" would reduce the amount of fats, the "bad energy dense heart killers" and keep the intake of carbohydrates constant (=high). This is probably also, the reason that the ostensible disproportionate lack of fats in the diets of the amenorrheic women vanished, once I weighted the data with the number of participants.

Figure 4: Total dietary intake of protein, carbohydrates and fats (in g; left) and differences between women with and without regular menses (right); data expressed either as simple group averages or weighed for the number of study participants (same sources as figure 3)

The picture that emerges after this adjustment has been done (figure 4, right, light bars) is clear and stands in line with my initial remarks on the primary of readily available energy in the form of circulating glucose, liver glycogen, and adipose tissue triacylglycerol, of which at least the former are way more readily derived from carbohydrates than fats.

And even the triacylglycers do, as the name implies, require a certain amount of glucose for the glycerol backbone (could be produced in the liver from amino acids and/or fats, though) and a minimal amount insulin to be stored in the fat cells (can be secreted in response to high amounts of protein and fat, as well, though).

So no fats? Just carbs and some protein?

Yet though carbohydrates have the availability bonus and proteins are necessary to maintain, better even build muscle mass, you would be ill-advised to steer clear of all dietary fats and, even more so the many good foods that contain them. Not so much because of the "essential" polyunsaturated fatty acid, though. According to a study by Tomten and Høstmark the dietary intake of PUFAs in 20 female runners with regular (n=10) and irregular (n=10) menses (LH levels of 7.6 vs. 2.9 IU/l!) was not statistically different. The intake saturated fats (-28%) and even more the intake of MUFAs (-38%), on the other hand was (Tomten. 2009) and the corresponding total fat-intake of 1.1g/kg body weight was obviously not sufficient to maintain optimal hormonal levels in the presence of a training volume of 7.5h per week.

What about vegetarianism? I know a few of you won't like this, but unless you are at least ovo-lacto vegetarian, i.e. a person who eats dairy and eggs, you are going to have a hard time fueling your athletic endeavors appropriately. After all, vegetarianism is associated with hormonal and menstrual abnormalities even in the non-athletic population, when they are dieting (Pirke. 1986). If you combine a mild energy deficit, as it is often seen in vegetarian, let alone vegan athletes, simply because it's harder for them to cover their energy and specifically protein and fat requirements without guzzling omega-6 oils and soy shakes all day (both not advisable, by the way), it is actually not surprising that Benson et al. mention vegetarianism right along low calorie intakes, nutritional inadequacies and low body fat stores as one of the main contributers to the (female) athlete triad (Benson. 1996).

Now you can certainly argue that all this comes down to the energy density and the correspondingly lower overall energy intake and could have been compensated for, if the women with menstrual irregularities had simply eaten more carbohydrates. In view of the fact that they didn't do so, I can hardly refute this argument. On the other hand, we have seen in the previous installment that an overexpression of GH and ghrelin is in as much part of the problem as too little insulin and a pathologically high insulin sensitivity. And some more fat in the diet (alongside carbs / not as the sole energy source!) couId in fact come handy to get that back in check.

Moreover, having a carb to fat ratio of ~2:1 (in energy equivalents) and a baseline fat intake in the range  of 80-100g (total) as the female runners with regular menses in the Tomton sudy had, has the beauty of never having to throw away the egg yolks, being able to get your share of fatty fish, full fat dairy, Kerrygold butter, virgin coconut and olive oil and beef or better calf liver as well as nuts once in a while. This in turn will allow you not just to stay sane and flexible with your diet, but also to satisfy your need for all those vital micronutrients you won't find in any of E-number laden fat-reduced garbage from the "low fat" shelves at the supermarket.

You see, in the end it all comes back eating simply more of the usual suspects, many people would probably file under "a paleo diet with lots of (safe) starches & fruit to fuel the energetic demands of a hard working athlete", these days.

If we think of the hypothetical daily energy requirement of 2000kcal/day which is often used as a reference for the nutrition information on those products of which you are going to buy less in the future (most real foods don't have nutritional information printed on them, you know ;-), the corresponding "numbers" could be anywhere on a continuum

• from 110g protein / 190g carbs / 100g fats, for someone without an endurance component in his workouts*, 
• to 100g protein / 240g carbs / 80g fats for someone who has a major endurance component and / or follows a high volume lifting routine*
  *pre- and post workout nutrition are not included, here!

This approach would ensure that you get enough protein, appropriate amounts of readily available energy, mainly in the form of safe starches and fruit, quasi unlimited amounts of vegetables and so much fat that you don't have to resort to the devastating "chicken breast, rice and broccoli diet", which will only worsen your situation.


References:

• Anderson KE, Rosner W, Khan MS, New MI, Pang SY, Wissel PS, Kappas A. Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man. Life Sci. 1987 May 4;40(18):1761-8.
• Benson JE, Engelbert-Fenton KA, Eisenman PA. Nutritional aspects of amenorrhea in the female athlete triad. Int J Sport Nutr. 1996 Jun;6(2):134-45.
• Laughlin GA, Dominguez CE, Yen SS. Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab. 1998 Jan;83(1):25-32.
• Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32(14):887-901.
• Pirke KM, Schweiger U, Laessle R, Dickhaut B, Schweiger M, Waechtler M. Dieting influences the menstrual cycle: vegetarian versus nonvegetarian diet. Fertil Steril. 1986 Dec;46(6):1083-8.
• Tegelman R, Aberg T, Pousette A, Carlström K. Effects of a diet regimen on pituitary and steroid hormones in male ice hockey players. Int J Sports Med. 1992 Jul;13(5):424-30.
• Tomten SE, Høstmark AT. Serum vitamin E concentration and osmotic fragility in female long-distance runners. J Sports Sci. 2009 Jan 1;27(1):69-76.
• Zanker CL. Regulation of reproductive function in athletic women: an investigation of the roles of energy availability and body composition. Br J Sports Med. 2006 Jun;40(6):489-90; discussion 490.

On Short Notice: Oxytocin to Boost Testosterone & Block Cortisol? Exercise for Life-Extension? Which Tea for Metal-Chelation? Which Fat to Reduce Calorie Intake by ~30%?

Image 1: This is still my preferred way to boost oxytocin - regardless of possible ergolytic effects ;-)

Due to the sudden heat-wave over here in good old Germany I thought, I'd use these early morning hours to get another installment of "On Short Notice" on it's way before my brain dries out (or I drown in the public swimming pool ;-). I hope you enjoy the four items on the recent interest in intranasal the hormone modulating effects of oxytocin, it's effect on cortisol and progesterone, estradiol and (I know you were waiting for that ;-) testosterone, my early morning / late evening (depending on whether you see this from my or Wyatt's perspective) 'intellectual' exchange on the potential longevity effects of exercise and why it probably is not life-extending in the literal sense, the different antioxidant potency of green, black and white tea and their ability to chelate metals (=help to remove all not just "bad" metals from the body) and the best fat, DHA or MUFA to blunt appetite and help you stick to your diet.

Don't forget to come back later today (or maybe early tomorrow for some of you ;-), for a third installment of "On Short Notice", which will hopefully suffice to "get rid" of the stock I have... ah, I did not forget about the Circadian Rhythm Series, by the way, it's just that the SuppVersity rhythm got slightly out of sync ;-)

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  Figure 1: Effects of 26IU of intranasal oxytocin at rest on progesterone, estradiol and testosterone in healthy men (large; based on Gossen. 2013); effects of 24IU or 48IU of intranasal oxytocin administered before a steady state cardio session on cortisol levels in healthy young men (small; from Cardoso. 2013)

  Intranasal oxytocin to block cortisol & boost testosterone A whole series of studies has been published recently; all of them have one thing in common, they investigate the various physiological and psychological effects of oxytocin. Of these, the two studies by Gossen et al. and Cardoso et al. are yet probably of greatest interest for the average physical culturist. After all, the researchers from the Centre for Research in Human Development at the Concordia University in Quebec (Canada) were able to show that the administration of 24IU (not the higher dose of 48IU, though;see figure 1) effectively reduced the increase in cortisol in a 70% HRmax steady-state cardio session in 17 healthy young men (aged 18–3; mean ± SD; 23.1 ± 3.5), in the experiment they describe in their Aug 2013 paper in Psychoneuroendocrinology (Cardoso. 2013).
  And even though the German scientists from the University of Aachen report minimal, but statistically significant increases in testosterone in 8 young men (mean age 26.4 ± 2.6 years) at rest, 210min after the (likewise) intranasal administration of a minimally higher dose (26IU) of oxytocin (Gossen. 2013). Both of these observations are not just very similar to what your average natty test booster is supposed to do, their real-world effects are probably also as insignificant. Also, did you ever try to tear down the gym and rep out a couple of PRs a couple of minutes after having sexual intercourse? If so, you should actually be aware why oxytocin probably ain't the ideal pre-workout supplement - in this regard it is also somewhat unfortunate that Cardoso et al. did not do a real performance test (suggested read: "Will Sex Before A Competition Hamper Your Performance"; note: this is not about sex minutes before the competition ;-).
  And when it comes to building muscle, previous research from Phillips lab at McMasters University appears to suggest that blocking cortisol is a hilarious idea, anyway. After tall, cortisol was the only endocrine hormone the elevation of which in the vicinity of resistance training sessions showed a positive correlation (r=0.29, P=0.03 cf. West. 2011) with increases in lean muscle mass in the large-scale by West et a.
• Exercise gets rid of the junk in your body, but will it help increase your lifespan? Basically this could be the headline to an interesting exchange of thoughts, I just had with Wyatt Brown on the SuppVersity facebook wall - one I believe is well worth being "recorded" as a short news item. The discussion came about in response to me posting the link to a study by He et al. who found that the way exercise induces autophagy (=natural, healthy cell death) contributes to its beneficial effects in the prevention of all sort of ailments, above all cancer and neurological problems such as Alzeimer's & co, because it allows your body to get rid of the debris and junk that's accumulating from just living your life (no matter how healthy or unhealthy that may be). Since exercise is not the only thing that can ramp up autophagy, and caloric restriction (as in starving yourself to live longer) can do the same, Wyatt mused about whether or not you could achieve the same (more or less; for animals vs. humans) proven benefits of life-long caloric restriction by exercise.

  

  Image 2: Twin studies are one of the ways to identify whether genes or lifestyle are the fundamental determinants of how old we get. One of the consistent findings of the numerous pertinent studies is that lifestyle factors (diet, exercise, but also our outlook on life, friends and family!) determine how well we are able to use the time that our genes (or whoever you want) has granted us on earth. Not more, but not less, either: If 100 years are what we got, all exercise and healthy eating will allow us to make it to that age with great ease, not more... and let's be honest, if that was the biblical age of 100y, wouldn't it be ungrateful to ask for more?

  A very good question, indeed and one I do not have a definite answer to. In view of recent reviews of the role of exercise in the longevity of centenarians (the oldest of the old; cf. Venturelli. 2013), it does however seem more likely that exercise does not have direct effects on the life-span, but, as Huffman states, "[e]pidemiologic evidence in humans supports exercise as a strategy to reduce the risk of morbidity and mortality" (Hufmann. 2010). Unfortunately, a low mortality won't help you to make it past the 100 ± X years your genes have in stock for you. The insights into the genetic determinants from pertinent studies into single-nucleotide polymorphisms (SNPs ~ single gene variations) does support this notion (Sorensen. 2013): The oldest of the old don't stick out, because their genes protect them from premature death, but simply because their genes allow for more cell cycles to occur before the 'natural reserve'. We already know that telomere length is a fundamental determinant of this 'reserve', so that it is not really surprising that telomere length at birth is one of the most reliable predictors of longevity (Heidinger. 2013)!
  Now, if we just use a totally random number to use basic math to make us understand, what this means, we could say that your telemore length at birth may be sufficient to make it to age 100, assuming that it is not prematurely shortened or you are dying from whatever other "natural" (not accidents etc.) cause, such as cancer, metabolic syndrome, CVD etc., exercise will of course help you to make it to those 100 years, but when the say 100,000 total turn overs that your telomeres allow for are done, you are done as well - no matter how "healthy" you eat and how much you exercise in the 99.99 years before. If you complement this "preventive" (=mortality reducing) effect by literally living on the slow lane, i.e. downregulating all your metabolic processes by starving yourself, you will obviously slow down the turn-over rate, as well. For simplicity of the calculation we assume that all these processes are linear (which I can guarantee they are not) and you are eating so little that you achieve a 50% slow down. That would mean that your turn-over rate would be reduced from 1,000 / year to 500 / year. Your reserves would last 2x longer and, assuming you eat and exercise and thus decrease your mortality risk, will allow you to make it to the ueber-biblical age of 200years! Great? Well you decide...

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  Image 3: If you want to get rid of metals, white tea should be your tea of choice, if you are already low on iron, copper, zinc & co. you should at least drink it away from your meals, though.

  Different tea preparations different effects antioxidant activity and metal chelation ability  It is nothing new that green and black tea will have differential effects on your physiology. What is yet a novelty is a comparison of the antioxidant and metal chelating activity the exact same hand plucked leaves of a specific cultivar (in this case PC108, bred in Malawi, typically used for black CTC tea production) will have when it is used for the production of either white, two black (Orthodox and CTC; both methods produce leaves of fannings or dust grades that are commonly used in tea bags, CTC = crush + tear + curl is processed by machines, while orthodox usually involves a mixture of mashine and manual processing) or two green (w/ and w/out caffeine) teas - a comparison like the one Patricia Carloni and her colleagues present in their latest paper in Food Research International (Carloni. 2013).
  As you will probably have expected the least processed green tea exhibited the greatest, while the most processed CTC black tea the least antioxidant activity (green ≥ low-caffeine green > white ≥ black Orthodox > black CTC), what may come as a surprise though is the superiority of white tea in the metal chelation essay the scientists performed. Closely followed by the orthodox black tea, the CTC tea (<50% of the white tea metal chelating activity) and the two green teas (<25% of the white tea metal chelating activity).

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  Figure 2: Reduction in calorie intake on standardized breakfast 20min after the ingestion of 6ml of a lemon flavored oil emulsion and in the course of the day compared to no oil control (based on Harden. 2013)

  Fat satiety effects: DHA > Olive Oil (MUFA) > regular diet That would be the ranking according to the satiety effects of the different fatty acids, as elucidated in a recently published study in the British Journal of Nutrition (Harden. 2013). For their study, the researchers had recruited 18 healthy normal-weight men. In a single-blind, three-way crossover study design the subjects received a single 6ml dose of either DHA or oleic acid (olive oil is 60-80% oleic acid, alternatives would macadamia ~60% and high-oleic acid sunflower oil >82%) with lemon flavor. The day before, the subjects had consumed standardized diets. 20min after the ingestion of the emulsion, they had a standardized breakfast, went home and went about their regular daily business for the rest of the day.
  The telephone interviews the researchers conducted on the next day showed that the ingestion of the DHA emulsion had exerted an, as the researchers argue cholecystokinin (CCK) dependent, decrease in energy intake of -20% and -29% for the breakfast and the total daily energy intake, respectively. That would make DHA a pretty effective tool to stick to my often-suggested -20% caloric deficit when you're dieting - at least for healthy individuals. Whether this will work for the obese, let alone morbidly obese with their deranged satiety signaling remains to be seen, though.

As I mentioned in the introduction, already. This was not the last "On Short Notice" item for this weekend. So, digest this, have some sex to calm down (unless you are about to work out, obviously), and drink a cup of tea to increase your chance to make sure that your end is not arriving before it's time and you can come back for more ;-)

References

• Cardoso C, Ellenbogen MA, Orlando MA, Bacon SL, Joober R. Intranasal oxytocin attenuates the cortisol response to physical stress: A dose-response study. Psychoneuroendocrinology. 2013 Aug 10. 
• Carloni P, Tianob L, Padellab L, Bacchettic T, Customud C, Kayd A, Damian E. Antioxidant activity of white, green and black tea obtained from the same tea cultivar. Food Research International. 2013.
• Gossen A, Hahn A, Westphal L, Prinz S, Schultz RT, Gründer G, Spreckelmeyer KN. Oxytocin plasma concentrations after single intranasal oxytocin administration - A study in healthy men. Neuropeptides. 2013 Aug 9. 
• Harden CJ, Jones AN, Maya­Jimenez T, Barker ME, Hepburn NJ, Garaiova I, Plummer SF, Corfe BM. Effect of different long­chain fatty acids on cholecystokinin release in vitro and energy intake in free­living healthy males. British Journal of Nutrition. 2013; 108:755­-758
• He C, Sumpter R Jr, Levine B. Exercise induces autophagy in peripheral tissues and in the brain. Autophagy. 2013 Oct 1;8(10).
• Heidinger BJ, Blount JD, Boner W, Griffiths K, Metcalfe NB, Monaghan P. Telomere length in early life predicts lifespan. Proc Natl Acad Sci U S A. 2013 Jan 31;109(5):1743-8. Epub 2013 Jan 9.
• Huffman DM. Exercise as a calorie restriction mimetic: implications for improving healthy aging and longevity. Interdiscip Top Gerontol. 2010;37:157-74. Epub 2010 Aug 10. 
• Soerensen M. Genetic variation and human longevity. Dan Med J. 2013 May;59(5):B4454.
• Venturelli M, Schena F, Richardson RS. The role of exercise capacity in the health and longevity of centenarians. Maturitas. 2013 Aug 7.
• West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2013 Jul;112(7):2693-702. Epub 2011 Nov 22.

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. 2013), 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. 2013)

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. 2013).

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. 2013)

  "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. 2013), 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. 2013).

  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. 2013).
  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. 2013). 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. 2013), 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. 2013).
  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. 2013) - 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. 2013).
• 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. 2013). 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. 2013). 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. 2013 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. 2013 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. 2013 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). 2013 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. 2013 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). 2013 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. 2013 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. 2013 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. 2013 May 6.
• Toss F, Wiklund P, Nordström P, Nordström A. Body composition and mortality risk in later life. Age Ageing. 2013 Jul 20.