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.

The Female(?) Athlete Triad - Part II/III: LH, GH, IGF1, Insulin, Ghrelin, Leptin & Co Form a Self-Perpetuating Vicious Cycle

I usually rant against pizza and beer, but once the athlete triad has struck, they can be an occasional part of the "healing protocol".

In last Sunday's first installment of this series we have taken a look at the prevalence, etiology and fundamental cause of an entity that is, and I am repeating myself here, profoundly mislabeled as the "female athlete triad". In fact, it is, as we have learned in the last installment, neither an exclusively female thing, nor a triad. If anything, it is a quintet or sextet. To make that clear, and give you guys, who make the same mistakes, but usually with less detrimental consequences, I will once more refer to it as "athlete triad" = AT,  in this second part of the Female(?) Athlete Triad Series in which we will take a look at the endocrine underpinnings of the previously described consequences of the temporary and long-term energy deficiency we have identified as the single most important causative factor of the onset of the "triad" last Sunday.

Which endocrine factors are figuring, here?

Instead of overwhelming you with the details right from the start, I decided to compile a list based on a cross-section of the dozens of articles I have read in the course of my eventually futile quest for a single definitive answer to the question, "Which hormonal or metabolic consequence of restrictive eating and excessive training is to blame for the fatigue, the low sex hormones concentration,the  bone resorption, the anemia, the absence of menses / lack of libido, the performance decreases and the whole string of pathological features, we have explored in the last installment?"

"Refeeding is not an option, because you will only become fat!" FALSE! Yet another myth without substantial scientific foundation that probably arises from the disturbed self-perception of those affected by AT and AN. In fact, the fat stores are the last thing that will be restored (Golden. 2004). This is probably also one of the reasons why "refeeding" often does not appear to work, because the basal energy requirements will increase with every pound of lean tissue you add back to your frame, so that athletes suffering from the "triad" will have to continuously increase their energy consumption. Unfortunately, most athletes will fail to do the former (also because exercise & stress can blunt hunger) and instead react with an increase in workout intensity, now that they are finally able to work out, again. This, in turn, will restore or even exacerbate the energy deficit and thus worsen not improve their physiological problems, even if their scale shows that they have already gained 5-10kg. If you take a look at figure 1 you will also realize that, at least in women, a baseline level of total (not relative!) body fat appears to be necessary to maintain regular menses (in men to maintain normal total testosterone & SHBG, but not so much free testosterone levels or reproductive function).

• low luteinizing levels are unquestionably among the elemental features and causally responsible for the occurance of menstrual disorders / lack of libido and the correspondingly low estrogen and testosterone levels in women and men
• TSH levels are not a valid / reliable indicator for the presence of absence of AT, because they can be both slightly increased or normal in the presence of low T4 and low T3 levels, as  - and this is far more often the case - TSH can be low despite low free thyroid hormone levels (usually in the presence of a low T3/rt3 ratio; if anything this would be a good indicator of beginning or full-blown AT)
• the circadian cortisol rhythm is whacked in men and women, alike; characteristic are the absence of an appropriate cortisol spike in the morning as well as the normal decline in cortisol levels  in the course of the day; metaphorically speaking, as the athletes triad progresses, the "mountain range" turns into mesa and eventually into a plane lowland
• the quartet of (mostly) sub-clinical hypogylcemia, low insulin, extreme high / or totally blunted insulin sensitivity, low IGF-1 and high catecholamine levels cannot be seen in isolation, most detrimental are yet probably the first and last of these four glucose-related players in the AT concert, as the former entails the constant risk to run out of "brain fuel" (in the absence of alternative fuel sources) and can - in the absence of adequate corticosteroid expression - become potentially life-threatening and the latter, i.e. low IGF-1 levels and very low IGF-1 to IGF1 binding protein 4 being one of the, if not the central factor involved in the the long-term physical decline of muscle, bone, organ and even brain mass.

As I have repeatedly emphasized in the last installment, the underlying cause, the trigger, maintaining factor and thus most important setscrew of the athlete triad (female or male) is an over-exaggerated and / or  long-lasting (weeks to months, in the worst case years; see Sundgot-Borgen. 2000) discrepancy between energy intake and expenditure, your body will initially try, but eventually fail to compensate by

• tapping into its energy stores in form of body fat, muscle and organ mass, the insulating fat around nerves and organs, etc.,
• continuously decreasing its metabolic activity (esp. thyroid metabolism),
• shutting down non-vital, but energy-intensive (e.g. immune and reproductive system) bodily functions, to prioritize short term survival of the individual over long-term survival and the conservation of the species

Therefore it is an indispensable and in many cases even sufficient prerequisite to restore an adequate supply of nutrients, and abolish temporarily better reverse the discrepancy between "energy in" and  "energy out" (please read the information in the red box next to the list of the previous paragraph, as well).

And what about leptin, ghrelin, adiponectin ... ?

Figure 1: In female athletes, only total fat mass, not body fat % or BMI are associated w/ AT (here identified by amenorrhea; top, left); the correspondingly low pulsatile (not baseline, see lower left) of LH correlate negatively with ghrelin and positively with leptin (top, right); while LH and leptin show a lack of pulsality, the ghrelin levels are not simply elevated, they also have a higher pulse size, amplitude and total polsatile secretion compared to control and eumenorrhetic athletes (bottom; LH, ghrelin, leptin expressed relative to non-athletic control; based on Ackerman. 2012)

Similar to the facilitative effects of the "hunger high", the "evolutionary advantage" that's turning its ugly face on everyone, who's willing to dig a deep enough whole (see Part I), the endocrine imbalances, as well as the reduced leptin) or over-pronounced (adiponectin) release of adipokines and the disturbances of the glucose, fatty acid and cholesterol metabolism start to take on a life of their own.

And as if that alone would not already make it difficult enough to separate cause and effect, it does actually appear likely that the order may even be reversed over time - not unlike the chicken that will hatch and eventually lay an egg. 

As discussed in the last installment, the combination of over-exercising and fasting, which may at time-point T0 actually have been the root cause of the problem will often turn into a strategy to stave off the impeding total breakdown. It becomes sort of a conditioned response to the constant starvation, which  will then no longer manifest itself in the form of hunger, but as anxiety and an almost compulsive urge to exercise (this is particularly well-established for anorexics; Teufel. 2008). And while the latter can be motivated by the desire to increase athletic performance and/or lose even more body fat, it does have a very real, often under-appreciated, physiological underpinning.

If you like, you could argue that the urge of the starved athlete to exercise is yet another "evolutionary conserved" automatism that mirrors the well-known food-seeking behavior rodents display  in periods of food deprivation and in response to the stimulatory effects of ghrelin on the orexin neurons in the brain (Yamanaka. 2003).

From ghrelin to growth hormone to IGF-1 and back

At the same time, the combination of exercise, low triglyceride, low free fatty acid and exuberant levels of the "hunger hormone" ghrelin leads to an overexpression of growth hormone (Scacci. 2003), subsequent increases in adiponectin (Wölfing. 2008), which will in turn decrease progesterone and androstenedione production and LH receptor expression in ovarian cells (Lagaly. 2008) and GnRH and LH release in the pituitary (Rodriguez-Pacheco. 2007; Lu. 2008). The surprisingly high adiponectin levels (surprisingly in view of the often dangerously low levels of adipokine producing body fat) will further increase the borderline pathological insulin sensitivity and thus lower the already rock bottom blood glucose and basal, as well as (post-)prandial insulin levels even further.

Figure 2: Illustration of the self-perpetuating vicious cycle of the athlete's triad (AT)

With their suppressive effect on leptin (Böni-Schnetzler. 1999), the high growth hormone levels and low body fat reserves are probably the most important contributers to the pathologically low, in fact quasi non-existent basal leptin secretion (see figure 1). And the low insulin levels don't just compromise the normal food-induced prandial suppression of ghrelin (Murdolo. 2003), they also hamper the production of IGF-1 (especially in the liver), so that athletes who suffer from the "triad" cannot derive any anabolic benefits from their high growth hormone levels, since the latter are largely mediated by the stimulatory effect of growth hormone on the production of IGF-1... what you are seeing here is thus a self-perpetuating vicious circle, you can extricate yourself from only by a multi-faceted approach the pillars of which are an..

* in view of the insulinogenic effects of whey and the pro-IGF-1 effects of casein (Hoppe. 2009), and the anti-catabolic effects of CLA & omega-3 you should - if by any means possible - incorporate dairy products from preferably grass fed dairy (butter, milk, cheese, yoghurt, quark / curd cheese, fermented dairy and if you want protein powders) in your diet regularly, better daily.

1. adequate and continuous energy supply to control ghrelin levels and help stabilize blood sugar (and thus glucocorticoid) levels and restore normal leptin and adiponectin expression,
2. increased low GI (to avoid reactive hypoglycemia) carbohydrate and protein intakes to normalize glucose levels, suppress ghrelin, increase insulin and IGF-1 levels* (Foster-Schubert. 2008; suggested read: "Carbohydrate Shortage in Paleo Land"),
3. balanced intakes of all types of natural fats, with an emphasis on long-chain PUFAs from food including a reasonable amount of "bad" omega-6 fatty acids and w/out fish oil or other omega-3 supplements, which would further blunt the already compromised glucocorticoid response and the leptin secretion (Kratz. 2002; suggested read "Omega-3 and Low Cortisol"), and
4. profound reductions in training volume to lower GH, cortisol, catecholamin and energy requirements and a (temporary) reorientation towards low volume strength training that will help increase bone density and IGF-1 expression (Davee. 1990)

Now, this may sound hilarious, but for the time being, laziness, pizza and beer - in moderation - are actually your friends. In that, I am not suggesting that you have to copy the patient, Chris Kresser mentioned several times on the old "Healthy Skeptic" podcasts (now RHR) about a client, who "cured" his longstanding physiological, and as I suspect psychological problems with pizza and beer, but the third pillar of this guy's regimen is actually a must: Go out with friends and start to enjoy your life again! Without thinking about food and exercise and sticking to whatever form of restrictive "diet" all the time.

Figure 3: Development of BMI (blue), leptin (red), adiponectin (green) levels in 8 female adolescent malnourished AN patients (based on Modan-Moses. 2007)

Apropos, third pillar. I have already had my short intense workout for the day, I have eaten well, but I have not hung out with friends. In other words, I will postpone the in-depth discussion of the energy and nutrient requirements, useful and detrimental supplements and medications, as well as necessary and facilitative tweaks to your workout routine to the next week, add another Roman "I" to the second "II" in "Part II/II" in the preliminary headline of this post and leave you (hopefully not too frustrated) with the graphical illustration of the effects re-feeding, alone, and a normalization of the body weight from a BMI of 16kg/m² to ~19kg/m² can have on the skewed basal leptin and adiponectin in figure 3.

In view of the fact that other studies have shown that this increase in weight, which must not be confused with a mere increase in adiposity, i.e. body fat percentage (go back to figure 1 if you already forgot that the absolute not the relative fat mass counts and please remember that the latter includes the fat in the myelin sheaths of your nerves, the protective fat around the organs, the fat in your brain etc.), does help with the normalization of both insulin and ghrelin (Otto. 2001), growth hormone and IGF-1 (Argente. 1997) and is in some cases even sufficient to restore most of the endocrine abnormalities (Scheid. 2010), many of the lessons we will learn in the next (and according to my current plans last ;-) installment can also be applied to a lean bulk - and that goes irrespective of your gender and your whether or not you have already fallen victim to the athlete triad!

References

• Ackerman KE, Slusarz K, Guereca G, Pierce L, Slattery M, Mendes N, Herzog DB, Misra M. Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls. Am J Physiol Endocrinol Metab. 2012 Apr 1;302(7):E800-6.
• Argente J, Caballo N, Barrios V, Muñoz MT, Pozo J, Chowen JA, Morandé G, Hernández M. Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation. J Clin Endocrinol Metab. 1997 Jul;82(7):2084-92.
• Beals KA, Manore MM. Disorders of the female athlete triad among collegiate athletes. Int J Sport Nutr Exerc Metab. 2002 Sep;12(3):281-93. 
• Boag F, Weerakoon J, Ginsburg J, Havard CW, Dandona P. Diminished creatinine clearance in anorexia nervosa: reversal with weight gain. J Clin Pathol. 1985 Jan;38(1):60-3. 
• Böni-Schnetzler M, Hauri C, Zapf J. Leptin is suppressed during infusion of recombinant human insulin-like growth factor I (rhIGF I) in normal rats. Diabetologia. 1999 Feb;42(2):160-6.
• Caspar-Bauguil S, Montastier E, Galinon F, Frisch-Benarous D, Salvayre R, Ritz P. Anorexia nervosa patients display a deficit in membrane long chain poly-unsaturated fatty acids. Clin Nutr. 2012 Jun;31(3):386-90.
• Davee AM, Rosen CJ, Adler RA. Exercise patterns and trabecular bone density in college women. J Bone Miner Res. 1990 Mar;5(3):245-50.
• Di Carlo C, Palomba S, De Fazio M, Gianturco M, Armellino M, Nappi C. Hypogonadotropic hypogonadism in obese women after biliopancreatic diversion. Fertil Steril. 1999 Nov;72(5):905-9.
• Di Luigi L. Does the high performance athlete need hormone replacement? Endocrine Abstracts. 2012; 29: 35.1 
• Foster-Schubert KE, Overduin J, Prudom CE, Liu J, Callahan HS, Gaylinn BD, Thorner MO, Cummings DE. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab. 2008 May;93(5):1971-9.
• Figueiro MG, Plitnick B, Rea MS. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults. International Journal of Endocrinology. 2012, Article ID 530726.
• Golden NH, Meyer W. Nutritional rehabilitation of anorexia nervosa. Goals and dangers. Int J Adolesc Med Health. 2004 Apr-Jun;16(2):131-44.
• Hernández M, Argente J, Navarro A, Caballo N, Barrios V, Hervás F, Polanco I. Growth in malnutrition related to gastrointestinal diseases: coeliac disease. Horm Res. 1992;38 Suppl 1:79-84.
• Hobart J, Smucker D. The Female Athlete Triad. Fam Physician 2000; 61:3357-64,3367. 
• Hoppe C, Mølgaard C, Dalum C, Vaag A, Michaelsen KF. Differential effects of casein versus whey on fasting plasma levels of insulin, IGF-1 and IGF-1/IGFBP-3: results from a randomized 7-day supplementation study in prepubertal boys. Eur J Clin Nutr. 2009 Sep;63(9):1076-83.
• Khan KM, Liu-Ambrose T, Sran MM, Ashe MC, Donaldson MG, Wark JD. New criteria for female athlete triad syndrome? As osteoporosis is rare, should osteopenia be among the criteria for defining the female athlete triad syndrome? Br J Sports Med. 2002 Feb;36(1):10-3. 
• Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan;8(1):21-34.
• Kratz M, von Eckardstein A, Fobker M, Buyken A, Posny N, Schulte H, Assmann G, Wahrburg U. The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women. J Clin Endocrinol Metab. 2002 Nov;87(11):5008-14.
• Lagaly DV, Aad PY, Grado-Ahuir JA, Hulsey LB, Spicer LJ. Role of adiponectin in regulating ovarian theca and granulosa cell function. Mol Cell Endocrinol. 2008 Mar 12;284(1-2):38-45.
• Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. Erratum in: N Engl J Med 1995 Aug 10;333(6):399.
• Loucks AB, Verdun M, Heath EM. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol. 1998 Jan;84(1):37-46.
• Loucks AB. Energy availability, not body fatness, regulates reproductive function in women. Exerc Sport Sci Rev. 2003 Jul;31(3):144-8.
• Lu M, Tang Q, Olefsky JM, Mellon PL, Webster NJ. Adiponectin activates adenosine monophosphate-activated protein kinase and decreases luteinizing hormone secretion in LbetaT2 gonadotropes. Mol Endocrinol. 2008 Mar;22(3):760-71. Epub 2007 Nov 15.
• Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32(14):887-901. 
• Mikos AE, McDowell BD, Moser DJ, Bayless JD, Bowers WA, Andersen AE, Paulsen JS. Stability of neuropsychological performance in anorexia nervosa. Ann Clin Psychiatry. 2008 Jan-Mar;20(1):9-13.
• Miller SM, Kukuljan S, Turner AI, van der Pligt P, Ducher G. Energy deficiency, menstrual disturbances, and low bone mass: what do exercising Australian women know about the female athlete triad? Int J Sport Nutr Exerc Metab. 2012 Apr;22(2):131-8.  
• Modan-Moses D, Stein D, Pariente C, Yaroslavsky A, Ram A, Faigin M, Loewenthal R, Yissachar E, Hemi R, Kanety H. Modulation of adiponectin and leptin during refeeding of female anorexia nervosa patients. J Clin Endocrinol Metab. 2007 May;92(5):1843-7. Epub 2007 Feb 27.
• Mont L, Castro J, Herreros B, Paré C, Azqueta M, Magriña J, Puig J, Toro J, Brugada J. Reversibility of cardiac abnormalities in adolescents with anorexia nervosa after weight recovery. J Am Acad Child Adolesc Psychiatry. 2003 Jul;42(7):808-13.
• Murdolo G, Lucidi P, Di Loreto C, Parlanti N, De Cicco A, Fatone C, Fanelli CG, Bolli GB, Santeusanio F, De Feo P. Insulin is required for prandial ghrelin suppression in humans. Diabetes. 2003 Dec;52(12):2923-7.
• NCAA® Sports Sponsorship and Participation Rates Report • 1981-82 – 2010-11.  
• Orlandi E, Boselli P, Covezzi R, Bonaccorsi G, Guaraldi GP. Reversal of bone marrow hypoplasia in anorexia nervosa: case report. Int J Eat Disord. 2000 May;27(4):480-2.
• Ott V, Fasshauer M, Dalski A, Meier B, Perwitz N, Klein HH, Tschöp M, Klein J. Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res. 2002 Nov-Dec;34(11-12):640-5.
• Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, Heiman ML, Lehnert P, Fichter M, Tschöp M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol. 2001 Nov;145(5):669-73.
• Rguibi M, Belahsen R. Body size preferences and sociocultural influences on attitudes towards obesity among Moroccan Sahraoui women. Body Image. 2006 Dec;3(4):395-400. Epub 2006 Sep 7.
• Rodriguez-Pacheco F, Martinez-Fuentes AJ, Tovar S, Pinilla L, Tena-Sempere M, Dieguez C, Castaño JP, Malagon MM. Regulation of pituitary cell function by adiponectin. Endocrinology. 2007 Jan;148(1):401-10.
• Scacchi M, Ida Pincelli A, Cavagnini F. Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. Front Neuroendocrinol. 2003 Jul;24(3):200-24.
• Scheid JL, De Souza MJ. Menstrual irregularities and energy deficiency in physically active women: the role of ghrelin, PYY and adipocytokines. Med Sport Sci. 2010;55:82-102.
• Schtscherbyna A, Barreto T, de Oliveira FP; Luiz RR, de Abreu Soares RR, Gonçalves Ribeiro B. Age of onset training but not body composition is crucial in menstrual dysfunction in adolescent competitive swimmers. Rev Bras Med Esport. May/June 2012; 18(3).
• Steinberg SE, Nasraway S, Peterson L. Reversal of severe serous atrophy of the bone marrow in anorexia nervosa. JPEN J Parenter Enteral Nutr. 1987 Jul-Aug;11(4):422-3.
• Skarda ST, Burge MR. Prospective evaluation of risk factors for exercise-induced hypogonadism in male runners. West J Med. 1998 Jul;169(1):9-12.
• Sundgot-Borgen J. [Physical activity and reproductive health]. Tidsskr Nor Laegeforen. 2000 Nov 20;120(28):3447-51.
• Teufel M, Zipfel S, Herpertz S, Zwaan M. (ed.). Handbuch Essstörungen und Adipositas. Springer Berlin Heidelberg. 2008. 
• Williams NI, Helmreich DL, Parfitt DB, Caston-Balderrama A, Cameron JL. Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J Clin Endocrinol Metab. 2001 Nov;86(11):5184-93.
• Wölfing B, Neumeier M, Buechler C, Aslanidis C, Schölmerich J, Schäffler A. Interfering effects of insulin, growth hormone and glucose on adipokine secretion. Exp Clin Endocrinol Diabetes. 2008 Jan;116(1):47-52.
• Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, Yanagisawa M, Sakurai T. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003 Jun 5;38(5):701-13.

The Female(?) Athlete Triad - Part I/III: How An Evolutionary Advantage Can Turn Its Ugly Face On Both Sexes!

The cover of the Vogue is usually not the place to turn to, if you are looking for role-models, but let's be honest: Do you believe Hope Solo or Serena Williams suffer from amenorrhea or their fellow Olympian Brian Lochte from low testosterone? I don't think so. So, there must be something "real" athletes do that way too many weekend warriors, who are in it, often to look just like their stars don't do - and in this multi-part SuppVersity Special, we are going to figure out what this may be.

I guess some of you will already have believed that I had forgotten about the requested and promised article on the "Female Athlete Triad". As you can easily see, this is not the case and still, I must admit that it will take another week until I will eventually have make good on my promise, as this is only the first part of a multi-part feature.

The main reason I decided to split things up is that I did not want you to simply skip on the fundamental information you will get today and fast forward to the potential solutions to the problem, I will present in the next installment.

After all, the idea of the SuppVersity is not to present cookie-cutter guru advice that may or may not work for you, but rather to put you into a position, where you do at least understand, at best have the skills to question, modify and tweak any exemplary "plans of attack" I will be outlining in upcoming the second part of this series... and if my past efforts to provide you with a basic understanding of your own metabolism have not totally failed, I would suspect that many of you will be able to come up with their own preliminary conclusions after reading this lengthy, but as I hope informative and not overtly complicated first part of the series.

"Female athlete triad:" How the problems start with a false label, already

But my bones are still strong! Specifically the inclusion of osteoporosis as an obligatory criteria for the diagnosis of the female athlete triad is nonsensical and was repeatedly criticized (e.g. Kahn. 2002), as it excludes a large, if not the major part of women (and men) who suffer from a syndrome the prevalence and consequences of which are thus largely underestimated. Moreover, in weight bearing sports, for example the load alone will counter the occurrence of osteoporosis, while other consequences like musculoskeletal injuries will be more prevalent.

So, let's initially take a look at what we are actually talking about here. The phenomenon itself is often somewhat misleadingly labeled as the "female athlete triad" (FAT; or AT w/out the sex-specificity), a term which falsely implies that it was sex-specific and men were immune to it and, what may be even worse, that it would be quite easy to diagnose as it comprises a "triad" of

• low energy availability / disordered eating
• amenorrhea, and
• osteoporosis

Unfortunately, things are much more complex than that and when an athletes health has been deteriorated so much, already, that amenorrhea (or very low testosterone in men) and osteoporosis are already showing their ugly faces, reversing the low energy availability and / or disordered eating, which usually goes hand in hand with months of overtraining, may be enough to keep the status quo, but won't reverse the amenorrhea and the underyling hormonal imbalance.

How prevalent is this misery?

Even if we don't extend our definition to include overall exhaustion and stagnating performance on the "harmless" and "heart disease" and "sudden cardiac death" on the other "life-threatening" end of the continuum, but simply include low testosterone levels and minor menstrual irregularities into our definition of AT (athlete triad), the answer to the above question is "It is rampant!" So rampant in fact that Luigi Di Florence chose the title "Does the high performance athlete need hormone replacement?" for a talk he held at a recent conference. In the respective abstract (a paper has not yet been published), he states:

Figure 1: Moroccan Sahraoui women still have a very different beauty-ideal than Western women. According to the data Rgubi et al. collected in 2006, their female beauty-ideal is heavier than the "health ideal". There is however a clear trend towards a "westernization" among the younger generation (data based on Rguibi. Now, tell me, where would you place yourself, your beauty-ideal and your health ideal on the graphic in the upper left hand of this figure?

"Exercise per se is associated to the release of different hormones: acute exercise stimulates an acute hormones secretion (e.g. catecholamines, growth hormone, CRH-ACTH-cortisol, testosterone) while chronic exercise (training) is able to modify hormones secretion at rest and their activation during acute exercise. [...] besides symptomatic classical diseases or conditions that may reduce/alter the qualitative/quantitative hormones secretion, serious clinical concerns exist for asymptomatic endocrine hypo-function (e.g. sub-clinical hypogonadism, growth hormone deficit and hypothyroidism), particularly in adult athletes. For example, in master athletes we observed an high prevalence of undiagnosed severe (12%) and mild (18%) hypo-testosteronemia frequently in the absence of clinical symptoms. [...] Unfortunately, few studies evaluated the prevalence of reduced hormones secretion in athletes and the concept of adapted hormone replacement in high competitive athletes." (Di Luigi. 2012; my emphases)

The absence of a clearcut definition of "the female athlete triad", the ignorance towards the existence of corresponding problems in male athletes (of all age groups!) and the vast differences within different study populations makes it very difficult to quantify, how many men and women actually suffer from AT. The little data we have is obviously sex-specific and of rather qualitative nature, as the following citation from Hobart 2000 goes to show you:

Although the exact prevalence of the female athlete triad is unknown, studies have reported disordered eating behavior in 15 to 62 percent of female college athletes. Amenorrhea occurs in 3.4 to 66 percent of female athletes, compared with only 2 to 5 percent of women in the general population. (Hobart. 2000)

If we take the latest NCAA numbers as a baseline (191,131 female athletes in the year 2011) and multiply them by 2x to include those lonesome gymrats and crossfitters out there who are often even more likely to overdo it than their co-ed peers who usually work with a more or less qualified coach, of whom you would expect that he or she is able to call a halt before it is too late, we are talking about ~13,000-252,000 young women and an undisclosed number of young men, here!

"Sh..Sh.. let's not talk about it!"

Pah, that's all not problematic! Really? A 2002 study from the Bell State University found that aside from the menstrual irregularity, which have been reported by 31% of the athletes not using oral contraceptives, both, muscle and bone injuries were rampant: 65.9% and 34.3%, in the aesthetic versus endurance and team/anaerobic sports, respectively. (data based on Beals. 2002)

Against that background it is almost careless, how little this topic is talked about - especially among athletes and fitness junkies! No wonder that only 10% of the 191 female exercisers (age 18-40 yr), engaging in ≥2 hr/wk of strenuous activity, Miller et al. questioned for their 2012 study on "the knowledge, attitudes, and behaviors of regularly exercising adult women in Australia", could name the initially mentioned three components of the female athlete triad:.

"Regardless of reported history of stress fracture, 45% of the respondents did not think that amenorrhea (absence of menses for ≥3 months) could affect bone health, and 22% of those involved in lean-build sports would do nothing if experiencing amenorrhea (vs. 3.2% in non-lean-build sports, p = .005)." (Miller. 2012; my emphases)

This lack of knowledge and - in parts - even downright ignorance towards the problem certainly raises the question:

"How do I actually realize I am about to develop the (female) athlete triad (AT)?"

I guess, we can derive a (not the!) answer to this question if we take a closer look at an overview of the etiology that has been part of a 2002 analysis by Melinda M. Manore from the Department of Nutrition and Food Management at the Oregon State University in Corvallis, Oregon, USA (see figure 2).

Figure 2: Etiology of the (female) athlete syndrome (and related pathologies) and signs you have to observe, in oder not to to realize what you have been doing when the potentially life-threatening long-term conequences, i.e. bone loss, cardiovascular disease and hardly reversible issues with reproductive function are showing (inspired by Manore. 2002)

I pimped the original graphic with a couple of remarks that should make one thing pretty obvious: At the very moment, when the "classic" features become obvious, it's actually already to late. The best you can hope for, when your menses start to disappear is that neither your cognitive abilities, nor your cardiovascular or bone health are not yet compromised, as well.

There is hope - even after the horse has bolted

"Men can't be anorexic?!" False! According to the latest data from the South Carolina Department of Mental Health there are currently 1,000,000 male US citizens suffering from eating disorders. Their estimated stake among anorexics and bulemics is between 10-15%. Among adolescents, anorexia is the 3rd most common chronic illness, and many of it's physical features are identical to those of the "female" athlete triad - not the least due to the fact that excessive exercise is often part of the pathology. The boundaries between them are fluid. The mortality rate associated with anorexia nervosa is 12x higher than the death rate of ALL causes of death: 5 – 10% of anorexics die within 10 years after contracting the disease; 18-20% of anorexics will be dead after 20 years and only 30 – 40% ever fully recover.

The good news is that our bodies (male and female) are self-repairing machines, evolutionary designed to take beating after beating - esp. if those "beatings" resemble periods of famine. From studies in anorexic men(!) and women we know that many of the pathological features of self-cannibalism (this, and nothing else is what your body is doing, when you constantly deprive it of an adequate supply of energy, as it is the case in the accute phases of the athlete triad) are reversible.

Mont et al. who have been following 31 severely underweight anorexic adolescents with body mass indexes of 15.2 +/- 2 kg/m², sinus bradycardia (=abnormally slow heart beat), decreased left ventricular mass, and diminished thickness of cardiac walls in 35%, 93% and 70%, respectively, report for example:

"After refeeding, a significant decrease in QT interval (p <.05) and QT dispersion (p <.01) was observed. Echocardiograms showed an increase in cardiac diameters (p <.01), left ventricular mass (p <.001), and cardiac output (p <.001). There was also an improvement in the exercise capacity (p <.05) and a normalization of the heart rate and heart rate variability (p <.05)." (Mont. 2012)

Allegedly, few athletes will maneuver themselves into a situation, where they are actually so weak that they can barely walk (which is unfortunately the case for way too many young anorexic patients), their susceptibility to sudden cardiac death and other CVD-related diseases is probably even higher, due to the exercise induced chronic overload of their cardiovascular system.

With the athlete's triad an evolutionary advantage is turning is turning against us

Athlete or not, even these severe physical abnormalities usually disappear with adequate rest, lots of patience and, most importantly, a progressive increase in energy intake (the increases in lean mass, i.e. muscle, organ and bone!, wants to be fed and the the metabolic switch from "energy save" to "normal" mode will increase the energetic demands even more). In fact, even in severely anorexic patients, where most of these pathologies are more severe than in athletes, renal abnormalities (Boag. 1985), atrophy of the bone marrow (Steinberg. 1987; Orlandi. 2000), cognitive impairment (Mikos. 2008) and most of the other functions that are related to survival (not reproduction!) usually recover with adequate energy intake, alone.

Without the evolutionary preserved, catecholamine and glucocorticoid driven "hunger high" our ancestors needed to keep going until they finally found something to eat, neither anorexia (AN), nor the athlete triad (AT) would "work".

The fact that many, if not most of the patients feel that the latter would not help and they would "just become fat", has both psychological, as well as physiological roots, which are related to (a) a distorted body image (which has by the way nothing to do with "being crazy", let alone "dumb" or "stupid") and (b) the loss of the "hunger high", which has previously been masking all the ailments and the total exhaustion and will begin to fade after only 1-2 days of sufficient energy supply and rest.

For many, it does in fact feel, as if they had just been hit by a truck, but in fact very truck has rolling right over them for years now and the person behind the steering wheel, was nobody else than the patient him-/herself.

Without the hilarious amounts of glucocorticoids (cortisol) and excitatory neurotransmitters their bodies seize producing, now that they are no longer necessary to keep the brain from dying a hypoglycemic death and the patients able and motivated to "seek for food" (another evolutionary preserved mechanism, by the way), all the weight of years of over-training and under-eating hits them all at once. In conjunction with the unwanted, but inevitable weight gain, of which Golden et al. state that it comes - specifically in this early phase - almost exclusively from increases in body water, organ, bone and muscle mass (Golden. 2004), this often triggers a relapse into the old "cosy" stress pattern of under-eating and over-exercising. And what's really nasty, here, is that this will provide (felt) "relief" within days, if not hours and via the exact same mechanism that has kept the patients going (and later alive!) over the past months and years: HUNGER (not workout) STRESS!

Not BMI, not fat, not exercise, but simply a constant state of energy deprivation is the culprit

Since we are all aware that weight gain does not happen over night, but the aforementioned perceived aggravation of fatigue can, it should be obvious that neither a low body weight, let alone the amount of body fat a person, man or women, is carrying on his/her frame (scientists refer to this as the "body composition hypothesis), nor the exercise induced stress ("stress hypothesis"), of which I have just outlined that it is a necessary and life-saving reaction to starvation, are at the root of the poblem. The true causative factor is (at least according to the current paradigm) the lack of a sufficient and constant supply of readily available energy (we are not talking about leafy greens and chicken breast, here!).

Evidence against the "body composition" hypothesis: After a surgical reduction of the stomach volume even obese women can develop amenorrhea

The most convincing evidence for the so-called "energy availability hypothesis", specifically in view of the hormonal aspects of the athlete triad, comes from a 1999 study on the short- and long-term outcomes of a surgical reduction of the stomach volume in severely obese women. Due to their artificially induced physical inability to consume adequate amounts of energy, these women, who were even after they had lost massive amounts of body weight still obese (BMI > 35!) developed amenorrhea (Di Carlo. 1999).

In this context, Anne B. Loucks who worked in the Department of Biological Sciences of the Ohio University in Athens, back in 2005, points out:

"Interest in the body composition hypothesis was rejuvenated several years ago by the discovery of leptin. Because leptin is secreted by adipose tissue cells, it was originally thought to signal information about the size of body fat stores. Rapid and profound declines in leptin were soon observed in response to fasting and dietary restriction, how-ever, and similarly extreme increases were observed in response to overfeeding and refeeding after energy restriction, all before changes in adiposity could occur. These observa-tions led to the revised hypothesis that leptin actually signals information about dietary energy intake. Since then, however, we have shown that the level and diurnal rhythm of leptin actually depend on energy availability (defined as dietary energy intake minus exercise energy expenditure) and that exercise itself has no suppressive effect on leptin beyond the impact of its energy cost on energy availability." (Loucks. 2005; my emphases)

In other words, the same hypothesis that initially pointed towards the amount of leptin secreting adipose tissue as a regulator of the hormonal balance in amenorrhetic women (the "body composition hypothesis"), does now, that it appears clear that energy availability and not body fat stores determine the secretion of leptin, clearly indicate that body fatness is a subordinate (as being the consequence of constant dieting) indicator of a persons susceptibility to suffer from hormonal imbalances, at best.

For similar reasons, the "stress hypothesis" which points with a finger at the exercise induced increases in cortisol is bullocks, as well. After all, those increases in cortisol and catecholamine expression are - just like low leptin levels - a necessary and healthy adaptation to the absence of a constant and adequate supply of energy. Without the glucocorticoids (just in case you still don't get it: "gluco" as in "glucose" <= the stuff everybody is scared about these days) no athlete or anorexic patient would be able to maintain normal blood glucose  - without any cortisol, they would simply die.

Evidence for the "energy availability hypothesis"

Figure 4: 24h-LH profile in healthy women after 5 days of normal (top) as well as calorically restricted (-33, -66, -87%) nutrient intake (arrows indicate meals, the black bar indicates sleep).

In fact, Loucks and her team at the Ohio University have conducted a whole series of studies the results of which support the "energy availability hypothesis" and I want to conclude this first part of the two-part series with the one study that segues directly into part II of this series, which will zone in on the the problem of persistent hormonal imbalances and their dietary and behavioral underpinnings.

In this regard, the profound disturbances in the pulsatile release of luteinizing hormone (LH) from the gonadotroph cells in the anterior pituitary gland, Loucks et al. observed after only 5 days of

• 33% - lower LH amplitude
• 66% - increased amplitude decreased frequency
• 77% - further decrease in frequency + increase in amplitude

calorie restriction, the scientists observed "regardless of whether energy availability was reduced by dietary restriction alone or by exercise energy expenditure alone" (Loucks. 1998) set the scene for a discussion that will be relevant for both, male and female physical culturists.

Don't forget to come back next week for part II!

In other words, if you want more about the role of the thyroid gland, of adiponectin and insulin sensitivity, of ghrelin and growth hormone, of insulin and IGF-1 and the circadian clock and intermittent fasting in the etiology of the athlete triad and which tweaks to your nutrition, exercise and supplementation regimen can help you not end up in a viscous circle that will not just hamper your perfomance, but compromise your physique and physical and psychological well-being, come back next Sunday for part II of the SuppVersity Athlete's Triad Special.

References

• Argente J, Caballo N, Barrios V, Muñoz MT, Pozo J, Chowen JA, Morandé G, Hernández M. Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation. J Clin Endocrinol Metab. 1997 Jul;82(7):2084-92.
• Beals KA, Manore MM. Disorders of the female athlete triad among collegiate athletes. Int J Sport Nutr Exerc Metab. 2002 Sep;12(3):281-93. 
• Boag F, Weerakoon J, Ginsburg J, Havard CW, Dandona P. Diminished creatinine clearance in anorexia nervosa: reversal with weight gain. J Clin Pathol. 1985 Jan;38(1):60-3.
• Di Carlo C, Palomba S, De Fazio M, Gianturco M, Armellino M, Nappi C. Hypogonadotropic hypogonadism in obese women after biliopancreatic diversion. Fertil Steril. 1999 Nov;72(5):905-9.
• Di Luigi L. Does the high performance athlete need hormone replacement? Endocrine Abstracts. 2012; 29: 35.1 
• Figueiro MG, Plitnick B, Rea MS. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults. International Journal of Endocrinology. 2012, Article ID 530726.
• Golden NH, Meyer W. Nutritional rehabilitation of anorexia nervosa. Goals and dangers. Int J Adolesc Med Health. 2004 Apr-Jun;16(2):131-44.
• Hernández M, Argente J, Navarro A, Caballo N, Barrios V, Hervás F, Polanco I. Growth in malnutrition related to gastrointestinal diseases: coeliac disease. Horm Res. 1992;38 Suppl 1:79-84.
• Hobart J, Smucker D. The Female Athlete Triad. Fam Physician 2000; 61:3357-64,3367. 
• Khan KM, Liu-Ambrose T, Sran MM, Ashe MC, Donaldson MG, Wark JD. New criteria for female athlete triad syndrome? As osteoporosis is rare, should osteopenia be among the criteria for defining the female athlete triad syndrome? Br J Sports Med. 2002 Feb;36(1):10-3. 
• Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. Erratum in: N Engl J Med 1995 Aug 10;333(6):399.
• Loucks AB, Verdun M, Heath EM. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol. 1998 Jan;84(1):37-46.
• Loucks AB. Energy availability, not body fatness, regulates reproductive function in women. Exerc Sport Sci Rev. 2003 Jul;31(3):144-8.
• Lu M, Tang Q, Olefsky JM, Mellon PL, Webster NJ. Adiponectin activates adenosine monophosphate-activated protein kinase and decreases luteinizing hormone secretion in LbetaT2 gonadotropes. Mol Endocrinol. 2008 Mar;22(3):760-71. Epub 2007 Nov 15.
• Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32(14):887-901. 
• Mikos AE, McDowell BD, Moser DJ, Bayless JD, Bowers WA, Andersen AE, Paulsen JS. Stability of neuropsychological performance in anorexia nervosa. Ann Clin Psychiatry. 2008 Jan-Mar;20(1):9-13.
• Miller SM, Kukuljan S, Turner AI, van der Pligt P, Ducher G. Energy deficiency, menstrual disturbances, and low bone mass: what do exercising Australian women know about the female athlete triad? Int J Sport Nutr Exerc Metab. 2012 Apr;22(2):131-8.  
• Modan-Moses D, Stein D, Pariente C, Yaroslavsky A, Ram A, Faigin M, Loewenthal R, Yissachar E, Hemi R, Kanety H. Modulation of adiponectin and leptin during refeeding of female anorexia nervosa patients. J Clin Endocrinol Metab. 2007 May;92(5):1843-7. Epub 2007 Feb 27.
• Mont L, Castro J, Herreros B, Paré C, Azqueta M, Magriña J, Puig J, Toro J, Brugada J. Reversibility of cardiac abnormalities in adolescents with anorexia nervosa after weight recovery. J Am Acad Child Adolesc Psychiatry. 2003 Jul;42(7):808-13.
• NCAA® Sports Sponsorship and Participation Rates Report • 1981-82 – 2010-11.  
• Orlandi E, Boselli P, Covezzi R, Bonaccorsi G, Guaraldi GP. Reversal of bone marrow hypoplasia in anorexia nervosa: case report. Int J Eat Disord. 2000 May;27(4):480-2.
• Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, Heiman ML, Lehnert P, Fichter M, Tschöp M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol. 2001 Nov;145(5):669-73.
• Rguibi M, Belahsen R. Body size preferences and sociocultural influences on attitudes towards obesity among Moroccan Sahraoui women. Body Image. 2006 Dec;3(4):395-400. Epub 2006 Sep 7. 
• Scacchi M, Ida Pincelli A, Cavagnini F. Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. Front Neuroendocrinol. 2003 Jul;24(3):200-24.
• Scheid JL, De Souza MJ. Menstrual irregularities and energy deficiency in physically active women: the role of ghrelin, PYY and adipocytokines. Med Sport Sci. 2010;55:82-102.
• Schtscherbyna A, Barreto T, de Oliveira FP; Luiz RR, de Abreu Soares RR, Gonçalves Ribeiro B. Age of onset training but not body composition is crucial in menstrual dysfunction in adolescent competitive swimmers. Rev Bras Med Esport. May/June 2012; 18(3).
• Steinberg SE, Nasraway S, Peterson L. Reversal of severe serous atrophy of the bone marrow in anorexia nervosa. JPEN J Parenter Enteral Nutr. 1987 Jul-Aug;11(4):422-3.
• Sundgot-Borgen J. [Physical activity and reproductive health]. Tidsskr Nor Laegeforen. 2000 Nov 20;120(28):3447-51.
• Williams NI, Helmreich DL, Parfitt DB, Caston-Balderrama A, Cameron JL. Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J Clin Endocrinol Metab. 2001 Nov;86(11):5184-93.

194 Bananas in 3 Weeks, Same Liver Fat & Lower Body Fat 6 Months After; Nigella Sativa Boosts Testosterone & Fertility; Sugar Dampens Caffeine Rush + Thyroid & Body Comp.

Three weeks of +1,000 kcal carb overfeeding (approx. 194 bananas!): Does it supersize your liver fat? This and more in today's installment of On Short Notice

As promised in yesterday's first part of the weekly written news-round up aka On Short Notice, we won't waste any time on lengthy introductions (the "short" items themselves are already long enough ;-) and get right down to business! For today this means that we are going to take a peak at the latest studies on

• the reality of thyroid hormone metabolism
• the dampening effects of sugar on high dose caffeine
• the sugary truth about the reversibility of early NAFLD
• the pro-testosterone, pro-fertility effect of black cumin

as well as the latest data on US drug sales and an upcoming blogpost discussing "training for anabolism" - enjoy!

Just in case you feel that's not enough, I suggest you listen to this week's installment of the SuppVersity Science News Roundup (click here to download) on Super Human Radio, as well!

• 

  Figure 1: The more energy reserves a metabolically healthy and euthyroid person has and the more he or she eats (though this was not quantified we can probably assume that the heavier participant also consumed more energy on a daily basis), the less energy efficient is his metabolism going to be - the margin is yet not unlimited, eat 40% more and get fat regardless of what type of food those calories come from (generated based on Roef. 2012)

  Levels of thyroid hormone associated with greater body weight and body fatness I know this sounds surprising, but int he end the latest results from the Department of Endocrinology at the Ghent University Hospital in Belgium only confirm what I keep preaching here at the SuppVersity over and over again: The main reason that the calories in vs. calories out calculations don't work is that the "calories out" part of the equation depends on both the "calories in" and the "calories stored", as well as the "accessibility of the calories stored" parameters, and [...].
  Put differently, the reason that the 941 generally healthy and euthyroid (=normal thyroid function) male siblings (25-45 yrs, median BMI 24.6) with the highest body weights and the greatest body fat mass also had the highest levels of leptin, free and total T3 & T4, as well as thyroid binding globulin is simple: In the presence of ample energy supply their bodies will treat their resources more wasteful, than those of the skinny or wanna-be-skinny, ah... I mean "ripped" guys who undereat and overtrain.
  The opposite is the case for the more muscular study participants, whose greater lean mass and muscle cross-sectional area were associated with lower (F)T3, (F)T4 and TBG levels (p ≤0.0003). They simply cannot afford (you could also say that they don't need) to ramp up their already higher fatty acid oxidation and overall energy expenditure, even further. Lastly, there was a clear-cut association with higher free T3 levels and lower insulin sensitivity, and - I had almost forgotten to mention that - "[n]o associations between TSH and body composition or metabolic parameters were seen."
  I suggest you print the finding about TSH levels and ask your doctor if he judges the speed of his car by looking at the gaspedal (TSH is more or less the gas-pedal that will tell your thyroid how hard it's got to work, but won't tell you how much of active thyroid hormone it is capable of producing) rather than the speedometer, when he is too cheap to order a full thyroid panel the next time you ask him to do so ;-)

• 

  Figure 2: While the initial caffeine spike is blunted by the ingestion of a sugar-laden breakfast, the area under the curve (bottom, right) a similar, yet less pronounced effect and both, the reduction of the initial spike in serum caffeine, as well as difference of the total influx over time are dose dependent (Skinner. 2012)

  Sugary breakfast reduces early rise in serum caffeine levels by up to 90% That's at least the result of a recent study by Tina Skinner and her colleagues from the University of Queensland in Down-Under. The high carbohydrate meal, in this case a toast with jam, cordial, and an energy bar ("Vanilla Crisp" PowerBar Performance Bar), the scientists served their 14 healthy active male participants (age 24.8 ± 3.7 yrs, body mass 74.6 ± 8.5 kg, height 184.0 ± 8.5 cm; mean ± SD) who had reported fasted, well hydrated and 48h after they had consumed their last caffeinated beverage at the lab (Skinner. 2012). It does not really take a rocket scientist to see that the absence of the initial onslaught of caffeine as a result of the pre-ingestion of the sugary "breakfast" will probably diminish, if not totally blunt the stimulating effects of coffee.
  In view of the fact that this effect was particularly pronounced during the "high dose" (=9mg/kg body weight; ~540-900mg; equiv. to 3-4.5 large cups of strong coffee), it is yet probably of greater importance for stim junkies and athletes looking for the pre-workout edge before they hit the gym, than for the average white color worker who needs to get his daily buzz, if he does not want to miss his bus (or train ;-)
• Liver-fattening effects of carbohydrate overfeeding are genetically dispositioned, but the recently published data from a study that was conducted by scientists from the Minerva Foundation Institute for Medical Research, the University of Helsinki and other Finnish research facilities shows that an appropriate diet can reduce increased liver and body fat levels, reduce body fat levels and improve lipid and glucose metabolism, regardless of the genotype (PNPLA3-148II = disadvantaged vs. PNPLA3-148MM) of the subjects.
  But let's take on thing after the other. After some standard baseline tests, the 16 subjects (mean age 54 year; BMI at baseline 30.6kg/m²; 5 men, 11 women) were "overfed" with a high carbohydrate diet from the "every low-carbers worst nightmare" category:
  

  

  Figure 3: Change in body composition from due to 3-week overfeeding (blue), 6 months dieting (compared to post overfeeding - red; Sevastianova. 2012)

  "The subjects were instructed to continue their normal diet and in addition to consume an extra 1000 kcal/d with 98% of energy from carbohydrates. The extra diet consisted of candy (Oy Karl Fazer Ab), pineapple juice (Tuko Logistics Oy), sugar-sweetened soft drinks (Oy Hartwall Ab), and/or carbohydrate-loading drink (Squeezy Sports Nutrition GmbH) and was provided free of charge from the research unit to the study participants." (Sevastianova. 2012)

  As you will probably have expected the highly insulinogenic, additional 21,000kcal from glucose and fructose (~5250g or 194 bananas, medium size to be precise ;-) did leave "their marks" on the waist and hips of the subjects, but probably not to the extend you may have anticipated (see figure 1). Even more suprisingly, the short term overfeeding did not deteriorate any of the blood glucose parameters (all changes had p-values way beyond what would be statistcally significant, the glucose clearance over 2h did even improve! - statistically likewise non-significant, though).
  Most importantly, however, the body composition, triglyceride levels (-6%), HDL (+11%) and all the important body composition measures (see figure 3) improved and the liver fat returned to baseline in the course of the 6-months "diet period", which consisted of - mark my words - nothing but making a switch to a diet with more vegetables, less simple sugars, white flour, and alcoholic drinks and dietary counseling wrt to food types and appropriate (=moderate) portion sizes. No extreme low carbing, no drastic calorie reductions, just healthy whole foods - regardless of "your bad genes"!
• Nigella sativa, aka black cumin, jacks up testosterone and makes tired sperm get a move on Being well aware that you cannot go without a weekly post about at least one natural testbooster,  you will probably be relieved to hear that Rahmatollah Parandin, Namdar Yousofvand and Rostam Ghorbani have published a paper in the latest issue of the Iranian Journal of Reproductive Medicine in which they describe the fertility and testosterone boosting effects of 200 and 400mg/kg of an alcoholic extract from Nigella sativa seeds (Parandin. 2012).
  *Reminder: Regardless of whether we are dealing with rodents or humans, a "testosterone booster" that works in sick animals or humans does not necessarily work in healthy ones, as well. It is much more likely, that the effects on testosterone are secondary to the effect of the effect the herb or whatever else has on the overall health of the lab animals / participants, so that someone who is not sick in the first place won't see any (or at best minimal) improvements.
  The seed extract that was administered to healthy*  male Wistar rats 60 days contained a mix of various active ingredients
  
  • 30-48% Thymoquinone,
  • 7-15% P-cymene, 
  • 6-12% Carvacrol, 
  • 2-7% 4-terpineol, 
  • 1-4% T-anethole, and 
  • 1-8% Sesquiterpene,
  of which Prandin et al. state that Thymogquinone is currently considered to be be the pharmacologically active constituent of N. sativa (cf. Padhye. 2008) - keep that in mind, when you cannot resist giving this stuff a try ;-)
  Now, the ~23% increase in testosterone is certainly nothing like the "140% increase in testosterone" certain supplement companies state one of the testers had (without any peer-reviewed data whatsoever, by the way), but as mediocre as it may seem, it was achieved from a healthy baseline level and it went hand in hand with improvements in all sperm parameters, of which I picked the sperm count and plotted it together with the latest human data from the University Department of Growth and Reproduction at the Rigshospitalet of the University of Copenhagen in Denmark in the second graph in figure 3 (Jørgensen. 2012).

  

  Figure 4: Yeah, Nigella boosts testosterone by 20% (left), but there are other things in life... what about it's effect on sperm count (right) for example? The increase the rodents in the high-dose group experients would catapult the infertile Danish men almost into the normal zone (based on Jørgensen. 2012 & Parandin. 2012)

  Now this is certainly by no means scientific evidence and I am not suggesting that it will help solve potential fertility problems (not just because sperm count is only one out of a dozen parameters, but also because we don't know whether what works in healthy rodents will work in sick people; see red box above for the other side of the coin). What I found quite important though, is to give you an idea of what those abstract numbers could eventually mean. Contrary to the 20% increase in testosterone which will hardly help you to build significantly more muscle mass, a similar bump in sperm count (and other fertility parameters) could very well make the difference between fertile and infertile!
  So, at whichever Internet source you may be able to dig up a respective extract and regardless of whether you want it for fertility or futility, ah... I mean "testosterone boosting" issues, make sure that it has a high Thymoquinone content and that you have enough of it to hit the human dose equivalent (click here to learn how to calculate HEDs) of 65mg/kg or 4-5g per day!
  

Figure 6: US Drug sales 2010 & 2011 as posted on the SuppVersity Facebook wall earlier today (based on Lindsay. 2012).

The End - for today, at least. I guess I won't take too much away, if I tell you that there was actually another item scheduled for today... a post about "High or Low, Long or Short, Heavy or Light what are the Best Set Numbers and Rest Times,Weights and Rep Schemes, When You're Training for Anabolism" - and while this is "anabolism" in the old and actually sort of outdated sense of more testosterone and less cortisol, I'm pretty confident that the muscle-heads among you would have liked it, if it did not get longer and longer, so that I decided to polish it up a little and put you on the rack for another two days or so ;-)

So, in case that's driving you crazy, you may want to consider asking your Dr. for a script for an antipsychotic, currently the #5 on the 2011 (=the latest) US drug sale ranking (see figure 6; remember the data is $-based not script-based), I posted along with a handful of other interesting news-items earlier today on the SuppVersity Facebook wall.

References:

• Jørgensen N, Joensen UN, Jensen TK, Jensen MB, Almstrup K, Olesen IA, Juul A, Andersson AM, Carlsen E, Petersen JH, Toppari J, Skakkebæk NE. Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men. BMJ Open. 2012 Jul 2;2(4).
• Lindsley CW. The top prescription drugs of 2011 in the United States: antipsychotics and antidepressants once again lead CNS therapeutics. ACS Chem Neurosci. 2012 Aug 15;3(8):630-1.
• Roef G, Lapauw BM, Goemaere S, Zmierczak HG, Toye K, Kaufman JM, Taes Y. Body composition and metabolic parameters are associated with variation in thyroid hormone levels among euthyroid young men. Eur J Endocrinol. 2012 Sep 6.
• Padhye S, Banerjee S, Ahmad A. Mohammad R. Sarkar FH. From here to eternity- the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond. Cancer Ther 2008; 6: 495-510
• Parandin R, Yousofvand N, Ghorbani R. The enhancing effects of alcoholic extract of Nigella sativa seed on fertility potential, plasma gonadotropins and testosterone in male rats. Iran J Reprod Med. July 2012; 10(4): 355-362.
• Sevastianova K, Santos A, Kotronen A, Hakkarainen A, Makkonen J, Silander K, Peltonen M, Romeo S, Lundbom J, Lundbom N, Olkkonen VM, Gylling H, Fielding BA, Rissanen A, Yki-Järvinen H. Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans. Am J Clin Nutr. 2012 Sep 5.
• Skinner TL, Jenkins DG, Folling J, Leveritt MD, Coombes JS, Taaffe DR. Influence of carbohydrate on serum caffeine concentrations following caffeine ingestion. J Sci Med Sport. 2012 Sep 7.