What's the Optimal Dose of Vitamin D3 for Lean, Normal-, Overweight & Obese Women With Established Vitamin D Deficiency to Get 25OHD Back into the Normal Range?

Both ladies are D-ficient, but will probably need profoundly different amounts of D3 to get their 25OHD back in range.

Actually, I guess, I don't really have to tell you that there is not going to be guest post by Adelfo Cerame, today. Adelfo is busy with the last weeks of school, but will be back as soon as he has passed all the tests. And while I am not sure, whether or not you would call the latest on vitamin D supplementation an adequate replacement for a contest prep update from "your's truly", I suppose that it's better than nothing to bridge the time that still remains until the SuppVersity  Science Round-Up on the Super Human Radio Network is going to air (the show starts at 12PM, EST; the Science-Round-Up airs in the 2nd hour and will thus begin at 1PM, EST; click here to listen live or wait for the podcast // update: now available).

I am honestly not yet sure what exactly we will cover today, but among the things I am still thinking about how we can squeeze them into a 1h show are...

• methylxanthines caffeine, theobromine and theophylline can bind to human DNA - what does that tell us about the purported health benefits of caffeine & co?
• caffeine prevents memory impairment - in this case in a model of sporadic Alzheimer's disease
• anti-Alzheimer's effect of CLA - plus a list of supplements that have been implicated in the prevention of Alzheimer's and other amyloid diseases such as Parkinson's, Cerebellar Ataxis, Amyotrophic lateral sclerosis and (hardly recognized as an amyloid disease) diabetes type II
• the effect of body weight on the benefits of circuit training in older women - turns out that those who need it the most, namely the obese, also see the greatest benefits
• Gum arabicum to ward off holiday weight gain - that this could actually work is at least what a recent human study would suggest
• more on vitamin E, resveratrol, soldiers don't get hurt in battle, but by geranium (DMAA), ...

I think there should be something for everyone of you. Plus: If everything works out, this is going to be the first show to air live via Skype, so no nagging land line echoes and noise any more.

Let's get to the D-news, now

The general consensus among the vitamin D advocates currently is that 2,000 IU of vitamin D3/day is the minimum you need to bring low levels of 25OHD back into the normal range. A soon-to-be-published study by Gallagher, Yalamanchili and Smith that's available ahead of print on the website of the Journal of Steroid Biochemistry and Molecular Biology does yet contradict this notion - at least for women with a body mass <25kg/m² even the meager RDA of 400IU would be enough (Gallagher. 2013). That said the concise paper actually describes the results of two, not just one experiment, with

• study 1 (ViDOS) being a one-year randomized, double-blind placebo controlled study (ViDOS – Vitamin D supplementation in Older Subjects) of increasing doses of vitamin D3 (400,  800, 1600, 2400, 3200, 4000 or 4800 IU/day vitamin D3 vs. placebo + calcium supplements to maintain calcium intake between 1,200-1,400mg/day) in 163 Caucasians, age 57–90 years; all vitamin D insufficienty, i.e. serum 25OHD ≤ 20 ng/ml (50 nmol/l), and 
• study 2 (STOP IT) being a 3-year intervention study of calcitriol 0.25 mcg (the active form of vitamin D) twice daily, conjugated estrogens 0.625 mg  daily, a combination of both and placebo in 488 elderly women, age 65–77 years

Body composition indices for the studies at hand (i.e. percentages of total and regional fat and fat-free mass) were measured by dual energy X-ray absorptiometry (DEXA Hologic Delphi) at baseline and after 12 months.

Figure 1: Mean total body weight, total body lean mass, total body fat mass and serum 25OHD in different BMI subgroups of study 2 (STOPIT); right, corresponding calculated ratios (based on Gallagher. 2013).

Even the baseline data in figure 1 does actually yield some insights into the relation of BMI, adiposity and 25OHD levels. While the data on the left already shows that the fat mass increases almost linearly across the BMI levels, while the lean mass remains relatively stable (with the highest value in the overweight group, though), the ratios I calculated and plotted on the right-hand side of figure 1 make it even more obvious clear: The lean / fat mass ratio scales with the BMI. With identical levels in the normal- and overweight individuals and significant increases and declines in the lightest and heaviest study participants. Moreover, the 25OHD vitamin D to fat mass ratio drops most significantly between the low BMI and the upper normal zone, where I suppose even most of the "healthy" individuals will be hovering around these days.

Being lean is a positive predictor of increases in 25OHD with supplementation

That this latent "chubbiness" of the average Westerner may be of particular significance in view of the negative / non-significant outcomes in many of the vitamin D supplementation trials, becomes self-evident, when you take a closer look at the data in figure 2, however you will have to realize that my plot which comprises above all the highly relevant relative changes (middle, marked in red) tells a different story than the original plot from the study showing only the absolute changes (left, but in form of a line graph).

Absolute, relative (compared to baseline) changes and total 25OHD levels (ng/ml) after supplementation with low, medium and high amounts of vitamin D3 in lean, normal, overweight and obese women (based on Gallagher. 2013)

Accordingly, the conclusion of the abstract, which says that "the response to vitamin D is dependent on body weight" and that "women with BMI <25 kg/m² develop much higher levels of serum 25OHD after vitamin D supplementation compared to those with BMI of >25 kg/m²" (Gallagher. 2013) may be correct, but is somewhat misleading as it is open to be interpreted as 'lean women respond most favorably to vitamin D supplementation' - an interpretation that is not really sustainable in view of the relative changes I calculated for figure 2  (middle), yet by no means as incredible as the abstract of another vitamin D study, I dessicated back in September (see "Stronger & Leaner or Fatter & Less Muscular W/ 4,000IU Vitamin D3 - What if Abstract and Data Tell Different Stories?")

Bottom line: The data from this most recent investigation into the differential response of lean, normal, overweight and obese women to vitamin D3 supplementation shows that the absolute increases appear on BMI and that...

• 

  Always take vitamin D with fatty foods! (see "A Fat D-Ficiency")

  low dose supplementation (400 or 800IU/day) is probably only sufficient to rise and maintain adequate vitamin D levels in lean women,
• medium dose supplementation (1,400 or 2,400IU/day) yields the most favorable outcomes in total 25OHD levels and 
• high dose supplementation (3,200, 4,000 or 4,800IU/day) does not yield additional benefits in either the the normal-, overweight and obese subgroup and only marginally higher levels in the lean women.

Overall the study at hand would thus support the notion that a daily vitamin D supplement containing ~2,000IU is the best way to get deficient levels back up, esp. for lean women it should be no problem to cut back to 2x the RDA, i.e. 800IU after normal vitamin D levels are achieved. For the rest, future studies will have to show if low dose supplementation is enough.

These longissimus dorsi slices of mice on a normal and a vitamin D3 supplemented diet show that supplemental vitamin D3 can be used as a fat synthesizer and meat tenderizer in "meat-producing animals". (learn more)

The often-heard hypothesis that the decreased response to vitamin D supplementation in the obese would be a result of the preferential storage of vitamin D in the adipose tissue was not supported by data of the Ghallagher study "there is no evidence from the dose response curves that in obesity serum 25OHD is being deposited in fat" (Gallagher. 2013). In view of the fact that contrary to total vitamin D, which is in fact preferentially stored in adipose tissue (78%) over lean muscle (14%), 25OHD stores are distributed much more evenly with 33% being stored in body fat and 20% in muscle tissue in omnivores like humans and swine (the data is in fact based on a study in pigs; cf. Jakobsen. 2007).

Lastly, a beneficial effect of increase / normalized vitamin D levels on lean or fat mass was (once again) not observed in any of the studies; and that despite the fact that "body fat was an independent predictor of serum PTH", which decreased in response to calcitriol supplementation in study 2 (which is actually more of an adjunct for correlative analysis and as a data source to compare the results of study 1 to). In other words, normalizing your vitamin D levels without taking appropriate measures to counter what's probably behind both, the nasty body fat and the low vitamin D level is not going to make you lean or musclar - at least as of now, it rather appears as if this was yet another instance, where we are - if anything - treating isolated symptoms instead of the root causes of the obesity epidemic.

References

• Gallagher JC, Yalamanchili V, Smith LM. The Effect Of Vitamin D Supplementation On Serum 25OHD In Thin And Obese Women. J Steroid Biochem Mol Biol. 2013 Dec 11.
• Jakobsen H, Maribo A, Bysted HM, Sommer OH. 25-Hydroxyvitamin D3 affects vitamin D status similar to vitamin D3 in pigs – but the meat produced has a lower content of vitamin D. British Journal of Nutrition. 2007; 98 908–913.
• Shephard RJ. Limits to the measurement of habitual physical activity by questionnaires. Br J Sports Med. 2003 Jun;37(3):197-206; discussion 206.

Classic Beats Super Slow; Single 198 Second Sprint More Time Efficient Than Work-Matched HIIT; Exercise Better Than THC; Metformin + Cardio + Lifting = Anti-Obesity Triplet; Self-Efficiacy & Training Adherence - Plus: More!

This is just a random selection of the unlimited movement patterns your body has been designed to execute - don't make the mistake and rely on only one of them!

The amount of really interesting, let alone revolutionary new studies on the effects of different exercise modalities is not exactly high, to say the least. I am not quite sure, what the reasons are, but as I have stated before, part of it certainly is that you cannot monetize on the results by producing patentable drugs based on your findings and will thus have a hard time to find sponsors / get funding. It is therefore no wonder that many published papers are spin-offs of small scale trials that have been conducted as part of dissertations. Others simply use rodent models, which may provide relatively reliable data, when it comes to the effects of running on a treadmill, but are not exactly what I would want to see, when it comes to weight lifting or any other of the myriad complex movement patterns our bodies can, but these days way too often don't do.

I have nevertheless been able to compile another potpourri of studies of which I would hope that one or the other will enlighten or at least entertain you. That being said, let's get started with this weeks installment of the Exercise Science Special of "On Short Notice", here at the SuppVersity...

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HIT it short, hit it hard, hit the glucose and be smart! Yo, this awesome rhyme would be my advice to the very busy chubby manager-types with compromised insulin sensitivity out there and it's based on the results of a very recent study by scientists from the Institute of Cardiovascular and Medical Sciences at the College of Medical, Veterinary and Life Sciences of the University of Glasgow in the UK (Whyte. 2013)

Figure 1: Power, workload (top) and metabolic effects of SIT and ES regimen (vs. control; bottom)

When Laura J. Whyte and her colleagues compared the effects of the single bout of very high-intensity exercise (SIT: 4x 30-s maximal sprints w/ 4.5min recovery between each) to a single maximal extended sprint (ES) matched with SIT for work done, they found that the immediate advantage of higher insulin sensitivity (measured via oral glucose tolerance test) in the work-matched continuous sprint the shorter duration 190s (TOTAL!) as well as almost identical...

• decreases is RER and carbohydrate oxitation, and
• increases in fatty acid oxidation

on the day after the exercise bout, in the presence of statistically significant reductions in insulin sensitivity only after the ES trial.

In other words: A single all out sprint on a braked cycle ergometer (as fast as you can; with obviously decreasing power in the course o the sprint) elicits greater metabolic effects within a 85% shorter timespan (198s vs. 1360s!), than work-matched classic HIIT training, with allegedly very long periods of active recovery.

That being said, I strongly caution against taking the results of this study as an incentive to perform the classic "go as fast as you can, for as long as you can" HIT sessions on exercise bikes, treadmills or ellipticals - those SUCK! *full stop* Be smart and either perform that one 3min sprint (if you really have no more time), or modify your HIIT training to incorporate longer high intensity phases (45-90s) at a work to active recovery ratio of 1:3 - 1:2, so that a resulting workout could look like that 4x 60s sprints, interspersed by 120s of active recovery. I would bet money that this protocol outperforms a work-matched continuous sprint in terms of its immediate and long-term metabolic effects.

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Opioid-like effects of exercise depend on intensity I guess you will be familiar with the term "runner's high"? Now, while the latter is usually ascribed to the exercise induced release of serotonin, the improved affect, the sense of well-being, the anxiety lowering and calming effects of exercise are probably mediated by the release of endocannaboids, of which scientists from the University of Arizona, the University of Texas Health Science Center and the Eckert College in St. Petersburg, Florida, have recently shown that the levels of these endogenous THC-like compounds depends on the intensity of the workout (Raichlen. 2013).

Liar, liar, THC junkie on fire ;-) You don't need to smoke weed before a workout if you get the intensity right! But could exercise also help people who recover from major depression to battle their tendency to obsess with negative thoughts and feelings?

At least in the 10 healthy regular runners who participated in the study, the results of which have been published in the Journal of Applied Physiology the endocannaboid exercise induced increase in circulating anandamide was most pronounced (~2x), when the subjects exercised at ~72% of their maximal heart rate (the workout consisted of 30min of treadmill walking, jogging, running at 45, 72, 83, and 92% of their maximal heart rate). Moreover, the post hoc analysis of the blood samples that had been immediately before and after the workout revealed that exercising at both the lowest and highest intensities had the exact opposite effect, although the reductions in serum anandamide were - when considered in isolation - were not statistically significant.

In conjunction with the results of another recent study that has been conducted at the Stanford University, it becomes evident that these results could actually be more than just "scientific masturbation", so to say. The Stanford researchers compared the reactions of 41 female patients who had recovered from major depressive disorder (MDD) and those of 40 healthy control, both of whom had been randomly assigned to either exercise for 15 minutes or quiet rest, to two sad mood inductions (once before and once after exercise or rest) and found that

"[while r]ecovered depressed participants who had not exercised exhibited higher NA [neagtive affect] after the second sad mood induction [...], both recovered depressed participants who had engaged in acute exercise and healthy control participants showed no increase in NA in response to the repeated sad mood induction." (Hogan .2013)

A reaction that goes against the so-called sensitization effect, which describes the tendency of depressed people (or people with a propensity to develop depression) to react with an increased level of negative effect to a repeated negative stimulus (Eisenstein. 2001) and would thus predict an increase in negative affect in response to the second stimulus as it was observed in the non-exercise group (figure 2, red box).

Figure 2: Negative and positive affect after 1st and second sad mood induction (left) and before and after exercise (right), respectively, in 41 female patients who had recovered from major depressive disorder (data from Hogan. 2013)

Moreover, the 15 minutes of exercise at an intensity the participant felt comfortable with led to an increase in positive affect participants in the exercise groups after the exercise bout, but failed to produce the same beneficial effect on the positive affect in the subsequent double-exposure to the filmic sad mood stimuli:

"However, in contrast to our hypothesis, we did not find any interaction between exercise condition and diagnostic group in level of reported PA following the repeated sad mood inductions that would be consistent with the notion of sensitization or habituation." (Hogan. 2013)

And who knows, if the exercise intensity had been higher, so that there had been more anandamide and other endocannaboids floating around in the brains of the study participants, this could even have changed the positive affect trajectory from the first to the second filmic sad mood induction? "Yo, that's so sad... hahaha" ;-)

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Image 1: Otsuka Long-Evans Tokushima fatty rats (OLETF, right) have a  genetic disposition to develop type II diabetes.

When metformin is good for the obese (pre-)diabetic and exercise is good, as well, metformin + exercise cannot be bad, right? At least in OLETF rats, one of the common rodent models of the metabolic syndrome, this assumption appears to apply (Jenkins. 2013).

According to the recently published paper by Nathan T. Jenkins and his colleagues, metformin and exercise do in fact work synergistically - at least as far as the obesity induced inflammation is concerned. While metformin decreased the pro-inflammatory overexpression of leptin, the rodents that have been exposed to an endurance type exercise regimen exhibited higher levels of the anti-inflammatory cytokine IL-10, which limit and ultimately terminate inflammatory responses (Moore. 2001).

Not just in view of the fact that IL-10 has also been implicated in the prevention and even treatment of auto-immune diseases, such as lupus erythematosus and multiple sclerosis (Beebe. 2002), I would always choose exercise over metformin - this is all the more true, if you are not morbidly obese in the first place!

And if you want to go even one step further, you simply add couple of interval sprints to the equation as those have been shown - in the same rodent model, by the way - to elicit greater improvements in HbA1c, the long-term marker of glucose management that "classic" steady state endurance exercise (Martin. 2013). Since the latter were mediated via differential microvascular changes than those Martin et al. observed in endurance trained OLETF rats, it is furthermore almost certain that they will add up. Probably not 1+1, but 1.5 and even 1.1 would still be better than 1.0, wouldn't it?

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The lack of the feeling of  self-efficacy is one of the best predictors of not sticking to a workout routine. And you know what? Oftentimes it's not your your, Joe or Jane who is to blame, but simply their cookie-cutter trainer or unqualified cousin who's dragging them to the gym. Now, think about that... could it be that you are a cousin / trainer like that!? No way, right?

A feeling of accomplishment is one of the main determinants of exercise compliance Have you ever wanted why you really enjoy going to the gym, while your obese cousin will only drag his ass over there if you kick him into the latter? Well, according to the latest study from the Johns Hopkins University School of Nursing and Division of Cardiology at the The Johns Hopkins University School of Medicine in Baltimore, Maryland, it may in fact be you and not Joe or whatever his name is, who is to blame. Probably you are just having him copy what you do, with either way too much weight, or so little weigh that he does not just feel bad about it, but cannot make real progress either (Nam. 2013).

The scientists call that which Joe is lacking a feeling of "self-effiacy", when he is going to the gym training next to his 75lbs lighter cousin, lifting sissy weights and looking like a fat balloon.

No wonder he is falling off the wagon! Specifically, if you also take into consideration that in addition to the missing feeling of accomplishment, which increases his chance of non-compliancy by 19%, Joe also exhibits most of the other features Nam et al. have found to increase the chance of dropping out, specifically,

• low fitness - 26% increased chance of dropout and
• higher insulin resistance - 17% increased chance of dropout,

in the course of their experiment with 140 overweight, sedentary individuals with type II diabetes, who were randomly allocated to a 6-month, 3 times per week exercise intervention or a non-exercise control. And while bodyfatness, i.e. a higher total and subcutaneous abdominal fat percentage appeared to be indicators of higher compliance, when the scientists just looked at the raw data, these positive effects vanished, when they plied a multiple logical regression analysis.

So what's the take home message, here? Cousin or not, people won't do well on cookie cutter plans that won't allow them to make, see and feel progress.

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Isn't it astonishing how versatile and important these stem cells from the bone marrow are (image NIH. 2001)

1h of exercise thrice a week increases hematopoietic stem cell (HSC) count in the bone marrow With the almost magic effects of stem cell therapy being on everybody's lips, these days. You will probably be intrigued to hear that researcher from the McMaster University have recently established that a very reasonable amount of 3x 1h of exercise per week increased the quantity of hematopoietic stem cells in the bone marrow of exercised mice by +20% compared to their sedentary peers (de Lisio).

With it's likewise statistically significant effect on the proportion of whole BM cells in G(2)/M phase of cell cycle (p<0.05 and an increase in the number of spleen colonies (+48%, p<0.05) in those "model patients" who received transplants from the exercised compared to transplants from sedentary mice, it is thus likely that people who exercise regularly will benefit from both the quantitative increase, as as well as the qualitative improvements these multipotent stem cells, which  give rise to all the blood cell types from the myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells), undergo in response to a moderate amount of exercise.

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Finally acknowledged: "[C]ombination exercise g[ives] greater benefits for weight loss, fat loss and cardio-respiratory fitness than aerobic and resistance training modalities", alone! And this is only the first part of the conclusion of a recently published paper by Suleen S Ho, Satvinder S Dhaliwal, Andrew P Hills and Sebely Pal, who explicitly suggest that

"Therefore, combination exercise training should be recommended for overweight and obese adults in National Physical Activity Guideline" (Ho. 2013)

How the scientists came to that conclusion? Well they could simply have read the SuppVersity news, but instead they conducted a 12-week trial, in the course of which 97 overweight or obese men (n = 16) and women (n = 81) (BMI >25 kg/m² or waist circumference >80 cm for women and 90 cm for men), aged 40 to 66 years, were randomly assigned to a either aerobic, resistance or combined training regimen (n=16 for each) or a sedentary control group (n=15). The results, spoke for themselves.

Figure 3: Changes in body fat (%; top) and VO2Max (bottom) in the course of the 12-week trial (based on Ho. 2013)

In the absence of statistically significant reduction in energy intake, or macronutient composition, the combination subjects in the combination group were the only ones to lose statistically significant amounts of

• body weight (-1.6kg),
• body fat (-1.9kg or 1% body fat), 
• android (=visceral) fat (-1.3kg),

had the most pronounced reduction in waist circumference (-2.6% vs. -2.5% in RT and -2.0 in AT) and were the only ones with statistically significant improvements in VO2Max, a marker of general cardiovascular fitness.

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Is there maybe more room in your training regimen for slow reps, than you may have thought? If you go by the statement "Slow speed-resistance training induced a greater adaptive response compared to training with a similar resistance at 'normal' speed" from a paper by Mark D. Schuenke and his colleagues from the University of New England, the Rocky Vista University, the College of Health Sciences and Profession and the Ohio-University that was published in the October Issue of the Journal of Applied Physiology (Schuenke. 2013), it would seem so.

If you do however take a closer look at the actual results you realize how important the adjoining qualificatory remark "However, training with a higher intensity at 'normal' speed resulted in the greatest overall muscle fiber response in each of the variables assessed" really is. After all, the "intensity" is per definitionem 20-45% higher in a classic strength training regimen compared to the often laughed at slow-speed resistance training (SS), which was - at least in the study at hand - defined as follows:

• SS: 6-10 reps, super-slow (10s) concentric (no typo!) and slow (4s) eccentric TUT, 40-60% of the individual 1-RM

Both the traditional strength training (TS) as well as the strength endurance regimen (TE) to which this protocol was compared used a TUT of 1-2s on the concentric and eccentric phase, but differed in terms of the weight and rep-numbers, which were

• TS: 6-10 reps at 80-85% 1-RM
• TE: 20-30 reps at 40-60% 1-RM

So, based on the qualificatory remark and a short glimpse on figure 4 you already know that the TS regimen yielded the best results during this 6-week resistance-training program that targeted the quadriceps femoris muscle group, in a total of 17 training sessions (only 2 in the first week), which were supervised to ensure that the 34 young, untrained female participants went to positive failure within the targeted repetition range on all three sets of the three exercises (leg press, squats, and knee extension) they performed after brief warm-up with ~2 min rest between sets and exercises.

Figure 4: Changes in body composition (left) and changes in muscle fiber cross-sectional area (all expressed relative to group baseline; data calculated based on Schuenke. 2013)

What's still missing though is the effect on overall body composition, where the super slow regimen did in fact produce almost identical results, while the "pump" workout ... ah, I mean the "strength endurance workout" sucked here just as it did as far as its effect on the increase in growth the number of hypertrophy-prone type II fibers is concerned.

So what's the take home message here? If you want some diversity, you can incorporate super slow sets into your regimen... but do you have to? At least based on the results of the study at hand, which was unfortunately conducted with untrained young women (who by the way love this alternative training styles) and is therefore not exactly representative for the average advanced trainee, the answer is "rather not, no!"

What neither the advanced nor the rookie who is striving to improve his or her body composition should do, however, is to train in the hilarious strength endurance range of 20-30 reps per set. If you want to build muscular endurance you either go out sprinting, beat the punching bag or do plyometrics.

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As I know you, you still want more, hah? Well, too much volume is not good for you and in case you cannot wait until next week, there will be some intriguing exercise news in the days to come, probably more on the SuppVersity Science Round-Up with Carl Lanore, on the Super Human Radio Network on Thursday, this week and obviously every day on the SuppVersity Facebook Wall @ www.facebook.com/SuppVersity - like it and always be the first to now!


References:

• Beebe AM, Cua DJ, de Waal Malefyt R. The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine Growth Factor Rev. 2002 Aug-Oct;13(4-5):403-12. 
• Eisenstein, E. M., Eisenstein, D., & Smith, J. C. The evolutionary significance of habituation and sensitization across phylogeny: A behavioral homeostasis model. Integrative Physiological & Behavioral Science. 2001; 36, 251–265.
• Ho SS, Dhaliwal SS, Hills AP, Pal S. The effect of 12 weeks of aerobic, resistance or combination exercise training on cardiovascular risk factors in the overweight and obese in a randomized trial. BMC Public Health. 2013 Aug 28;12(1):704.
• Jenkins NT, Padilla J, Arce-Esquivel AA, Bayless DS, Martin JS, Leidy HJ, Booth FW, Rector RS, Laughlin MH. Effects of Endurance Exercise Training, Metformin, and their Combination on Adipose Tissue Leptin and IL-10 Secretion in OLETF Rats. J Appl Physiol. 2013 Sep 27. 
• de Lisio M, Parise G. Characterization of the Effects of Exercise Training on Hematopoietic Stem Cell Quantity and Function. J Appl Physiol. 2013 Sep 27.
• Martin JS, Padilla J, Jenkins NT, Crissey JM, Bender SB, Rector RS, Thyfault JP, Laughlin MH. Functional adaptations in the skeletal muscle microvasculature to endurance and interval sprint training in the type 2 diabetic OLETF rat. J Appl Physiol. 2013 Aug 23.
• Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683-765.
• Nam S, Dobrosielski DA, Stewart KJ. Predictors of Exercise Intervention Dropout in Sedentary Individuals With Type 2 Diabetes. J Cardiopulm Rehabil Prev. 2013 Sep 24.
• National Institute of Health (NIH). Stem Cell Information Webpage. June 17, 2001. < https://stemcells.nih.gov/info/2001report/chapter4.asp > retrieved on Oct 01, 2013.
• Raichlen DA, Foster AD, Seillier A, Giuffrida A, Gerdeman GL. Exercise-induced endocannabinoid signaling is modulated by intensity. Eur J Appl Physiol. 2013 Sep 19.
• Whyte LJ, Ferguson C, Wilson J, Scott RA, Gill JM. Effects of single bout of very high-intensity exercise on metabolic health biomarkers in overweight/obese sedentary men. Metabolism. 2013 Sep 19.

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. 2013; 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 2013 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. 2013; 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. 2013)

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. 2013; 29: 35.1 
• Figueiro MG, Plitnick B, Rea MS. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults. International Journal of Endocrinology. 2013, 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. 2013 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 2013; 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.

Exercise News Round-Up: The Latest on Weight Lifting, Steady State, HIIT, Pyramid Training & Co, Their Effects on Body Composition, Leptin, Muscle Morphology & More

Running may be the "original exercise", but there is more to physical culture than that - irrespective of your gender, by the way; HIIT would be one thing, weight lifting the other that must not be missing from your regimen which can yet still benefit from one or another classic cardio session (img womanshealthmag.com).

I must admit that I am a bit lazy today and not really in the mood of writing a lengthy post on circadian rhythms. The weather is awesome and I think I'd better spend the time in the sun recharging the batteries of my circadian clock, than sitting in front of a computer screen.

Since I do know that the former, i.e. the good weather won't apply to all of you and that reading these posts does not take anywhere as long as writing them, I will yet put together the promised post on "exercise news" - and I can tell you there is half a dozen of them, such as

• liver health, aerobics and strength training
• no leg-based cardio on leg day
• aerobics alone won't cut it
• intramuscular arguments in favor of HIIT 
• reverse or classic pyramid about equally effective
• intense exercise has leptin plummeting

You see, more than enough for one day, so we better get right down and dirty... ah, I mean, sweaty - yeah, sweaty ;-)

• Putting weights into the equation squeezes the fat out of your liver and belly In a recently conducted study into the effects of long-term exercise on the weight and fat loss in post-pubertal overweight adolescent with non-alcoholic fatty liver disease, the combination of aerobic and resistance training was "more effective in significantly improving noninvasive biomarkers of NAFLD that are associated with the highest risk of disease progression in the pediatric population" (de Piano. 2013). The main facts about the program
  

  

  Figure 1: Only combined aerobic and resistance training offers the body recompositioning effect we are all looking for: more muscle, less fat - and that works optimally, only, if your liver is still fully functional (de Piano. 2013)

  • one-year intervention + dietary counseling
  • 60min of personalized aerobic training, or
  • 30min aerobic + 30min resistance training
  • performed three times a week

  In the abstract of their study the scientists unfortunately fail to point out that the additional resistance training, which consisted of a standardized, progressive full-body training with 3 sets of 6-20 reps (depending on exercise) had the extra bonus of building more muscle and cutting more body fat than the less versatile three times pe -week 60min aerobics program.
  Moreover, the fact that only the participants in non-NAFLD, "just obese" control group were able to increase their muscle mass, goes to to show you, how important an optimally functioning liver actually is, when it comes to building muscle, losing weight and staying healthy.

• 

  Image 2: If you train legs with a similar volume as Arnold & Franco did, back in the day, you don't want to and probably also don't have to do any additional cardio before or after your workouts.

  Doing 30min of cardio on the elliptical reduces the number of reps you will be able to perform on a subsequent leg workout, but the bench press performance won't suffer. That's the very unsurprising result of a hitherto unpublished dissertation by Jeremy Tan from the University of California in Fullerton (Tan. 2013).
  Tan had recruited twelve young men who had completed four trials in random order. In two of those trials the guys performed 30min on the elliptical machine at 70% of their age-predicted (not measured!) HRmax followed by either 3 sets of back squats or bench presses performed to failure at 75% of their predetermined 1RM - not exactly an "Arnold-esque training volume, anyway, right (see image 2)?
  Bottom line: Better don't do a lengthy cardio workout before your leg training - but also: Don't believe the bro-scientific myth that 30min of cardio were so exhausting (systemically) that you could not train a body part that was not heavily involved in the cardio session (in this case the upper body), afterwards.

• 

  Figure 2: Cardio alone won't change your body for the better and the changes in CRP and leptin are not statistically significant (data expr. rel. to baseline; based on Bijeh. 2013)

  Aerobics alone won't really cut it and this goes not just for advanced male athletes, but even for middle aged (42y) women (BMI 25-27) who have never trained before. At least this is what the results of Bijeh, Hosseini and Hejazi from the University of Mashhad (Iran) would suggest, because even after 6 months with 3x 60 minutes (55-65 HRmax) none of those body composition parameters women are usually trying to improve, when they are taking up an exercise regimen did come about (Bijeh. 2013): Other than a minimally, but statistically non-significant reduction of body fat a prominent but not significantly different (P=0.2 for the variation) increase in leptin levels in the exercise group were the only "beneficial" changes the "workouts" brought about.
  Plus, in how far the increase  in leptin actually is a good thing does still remain to be seen, also because the CRP levels (inflammatory marker) in the training group increased (likewise not statistically different) and the allegedly statistically significant difference in the waist to-hip ratio (-0.01 in the aerobics group vs. no change in the sedentary control) of the women is so small against the standard deviations of the respective value that I am not sure about how significant it really is - regardless of what ANOVA, a program that's often used to do the statistics on data like that, say.
  Bottom line: If for whatever reason you can only do light "classic cardio" there is no way it will make a difference if you don't combine it with a sound dietary regimen.
• HIIT and classic endurance training equally effective in increasing muscle microvascular density The latest study from the UK shows that HIIT is more and more being accepted by researchers as a viable alternative to the classic aerobic training programs. In a 6-week intervention, Cox et al. assigned 16 young previously sedentary men (age 21±0.7 yrs, BMI 23.8±0.7 kg/m²) randomly to either 40-60 min cycling at ~65% VO_2peak, 5 times per week (ET), or a much less time-consuming HIIT protocol that comprised 4-6 Wingate tests, 3 times per week (HIIT).

  

  Image 3: While the study used the classic wingate test protocol with a stationary bike you can also do 30s all-out sprints, use a spinning bike or whatever else allows for maximal efforts and temporary exhaustion without you hurting yourself or the equipment breaking down (or both ;-)

  Other than most of their colleagues the scientists were yet less interested in the beneficial effects this exercise would have on VO2Max, let alone simple weight loss, but analyzed muscle samples for their microvascular endothelial eNOS and NOX2 content (indicative of the vascularization) and the actual morphological capillarization of the muscle by quantitative immunofluorescence microscopy. Whole body insulin sensitivity, arterial stiffness, and blood pressure were also assessed.
  The results showed that both protocols were equally effective in inducing the adaptive changes in microvascular capillarization and NOX2 expression, while the short intense exercise bouts during the HIIT protocol yielded 12% greater increases in eNOS content (ET 14%; P<0.05, HIIT 36%; difference p < 0.05).
  Now, eNOS is actually better known for its preventive role in CVD (and hypertension), but its negative correlation with body fat levels (higher eNOS <> lower body fat - note: this is almost certainly not a causal relationship(!); cf. Hickner. 2006), its central role in the maintenance of exercise capacity (Lee-Young. 2009) and its putative role the maintenance of mitochondrial function and integrity into the old age (Chanséaume. 2009) it should be obvious that time-efficiency is not the only thing that speaks in favor of HIIT, here. 

• 

  Figure 3: Strength gains (no idea what the scientists mean by "compression", just think about it as the effect size) of 6 weeks, 18 lifting sessions, employing a classic or reverse pyramid loading scheme on chest (bench press), quads (leg extension) and biceps (curl) strength (adapted from Bostani. 2013)

  No statistical significant differences in strength gains between classic and reverse pyramid While Bostani and Shariati did in fact not find statistically significant differences between the strength gains of their physically active, but "non-athlete" (sic!) study participants (N=10 for the two active and the control arm) a closer look at the data in figure 3 to the right does still reveal that it could make a difference, whether increase the weight from set to set (regular pyramid) or decrease it from set to set (reverse pyramid) - at least for your extremities, with the quads responding more favorable to the reverse pyramid and the biceps to the classic pyramid training.
  If the study was not so hilariously poorly described and the translation so sloppy, I would love to use these insights for a recommendation on how to train.
  In the absence of set number, reps and everything else that would be necessary, I can yet just say that this appears to confirm my personal experience, which tells me that you have to hammer your legs to grow and get stronger, while the classic pyramid with it's generally lower overall volume matches the "hit it hard and short" approach that appears to work best for biceps, in the longer run.

• 

  Figure 4: Eight weeks of intense exercise in the presence of a negative energy balance (as evidenced by the weight loss) take their toll on leptin levels, it is yet not sure for whom that's a bad thing (data based on Ferdosi. 2013)

  Intense exercise will make make your leptin levels drop and that irrespective of whether you do endurance training, strength training or both! That's the long and short of a study that has been published in the latest issue of Procedia - Social and Behavioral Sciences (Ferdosi. 2013), which did not even find a quantitative difference between the effects 8 weeks of 3 session of either 40 minutes (increasing from 25 in the first two, to 35min in weeks 3-6 and 40min in weeks 7-8) cycling at 75-85% HRmax (aerobic), a standard full-body workout (resistance) or both strength and aerobic training concomitantly (concomitant).
  It is thus obvious that done at a high enough intensity and in the presence of a negative energy balance, the same endurance exercise that elicited an increase in leptin in the Bijeh study (remember, this was more of a leisurely walk and without a build-in progression) will decrease leptin levels significantly.
  Now, that's great if you got a lot of fat to lose and are leptin resistant anyway, if you are yet lean already (with a BMI of 29kg/m² the healthy but untrained 48 male study participants, here, were not exactly ripped, but far from being obese) this can become a problem that could not just forestall fat loss, but could precipitate endocrine imbalances - and that's nothing that can only happen to women, in whom it usually manifest as amenorrhea (Christo. 2008)

That's it for today, but since I know you will be asking, yes, there I will catch up with the circadian rhythm series and yes I understand that the last item of today's installment has left at least some of you very dissatisfied. So, yes, I will finally address the issue of amenorrhea (but also hypogonadism in men) in an individual post, although I still don't have the clearcut "do this, don't do that" solution to the problem, I wanted to find before, I write the respective post... ah, and in case neither of those things does interest you, don't worry there will of course be other posts in the next days, as well ;-)

References:

• Bostani M, Shariati M. The Comparison of Between the Effects of Two Training Methods on Dynamic Strength of Non-Athletes Males Procedia - Social and Behavioral Sciences. 2013; 46: 417–420
• Bijeh N, Hosseini A, Hejazi K. The Effect of Aerobic Exercise on Serum C - Reactive Protein and Leptin Levels in Untrained Middle-Aged Women. Iranian J Publ Health. Sep 2013; 41(9).
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