Organ Specific Resting Metabolic Rates and Diet-Induced "Metabolic Damage". Plus: At Rest Heart, Liver & Kidney Consume 83x More Energy/kg Organ Mass Than Muscle

No, your muscles are not the primary gas guzzler in your body.

The problems arising as a consequence of a diet-induced reduction of the metabolic rate are among the recurring themes here at the SuppVersity. For a good reason, as I would say. After all, they are the #1 reason for weight loss plateaus and the yoyo effect. Although the notion that "calories count" is not very popular these days there is no debating that an energy deficit is a necessary prerequisite for weight loss. The problem however is that you cannot determine your energy balance with a calculator, a body fat caliper and a scale. There are way too many other factors involved - the amount, macro- and micronutrient composition, timing, frequency, volume, texture and palatability of the ood you eat, stress, hormonal factors, etc - all of which will affect the amount of energy you expend and subvert the results of over-simplistic calories-in vs. calories-out calculations.

What are the most notorious gas guzzlers in our body?

Things would actually already be complex enough, if we focused solely on that "input" <> "output" recursion, but unfortunately, even the notion of a "global" (=valid for the whole body) metabolic rate is nothing we can really rely on. If we wanted to have a somewhat more accurate estimate of our basal energy requirements, i.e. the amount of energy we need if we don't move all day (which is basically what the average Westerner does, these days ;-), we would have to know the individual energy requirements of all our major organs and add them up, using a formula like this:

The more you eat, the more you burn. You can find more evidence that men & women are no bomb-calorimeters here

240x brain mass in kg

+ 440x heart mass in kg
+ 200x liver mass in kg
+ 440x kidney mass in kg

+ 13x skeletal muscle mass in kg
+ 4.5x adipose tissue mass in kg

+ 12x residual mass in kg

This formula, which was developed based on studies of Elia et al. in 1998, assumes that the metabolic activity of an organ increases linearly with its mass and that the specific metabolic rates (ki-values, i.e. 240 for the brain, 440 for the heart, etc.) are accurate. In the average, normal weight non-dieting individual these values are constant and have been confirmed lately in a set of experiments that were conducted by Wang et al. (see figure 1)

Figure 1: ki-Values of adipose tissue, skeletal muscle, liver, brain, heart, kidneys, residual volume from the Wang studies; all values expressed relative to the reference values from Elia (1998)

These studies, which were published subsequently in 2010, 2011 and 2012, also reported that there are distinct trends for decreasing ki-values and thus lower resting energy expenditures at identical organ masses in both obese / lean and older / younger individuals - an effect which can be explained by either lower cellularity or lower specific metabolic rates of the respective organs and tissues. In light of the fact that the "organ weight x ki-value"-calculations are very accurate and that

"there is only a small and nonsignificant difference between REEm [measured resting energy experience] and REEc [the energy experience calculated based on ki-values and organ masses] of about 13 to 80 kcal/day" (Müller. 2013b)

it should be obvious that both aging and already being obese put you at a higher risk of weight gain in a society where energy dense foods and large portion sizes are the rule, not the exception.

Is there something like organ specific metabolic damage?

A couple of recent studies have investigated the effects of weight loss and regain on organ-specific energy expenditure in order to find out if this may be the, or at least one of the underlying reason for the reduced resting energy expenditure in formerly obese individuals (Müller. 2013a; Bosy-Westphal. 2009 & 2013). These studies support the idea of a fall in the organ size and weight and the corresponding ki-values of high metabolic rate organs (heart, kidney, liver) with weight loss. Bosy-Westphal (2009), for example report a -136kcal/day reduction in resting energy expenditure (REEm = measured) with 4-6% loss of liver, heart and kidney mass in obese women after 9.5kg body weight loss (2.6% fat free mass).

Figure 2: Difference between measured and calculated energy expenditure in MJ/day at baseline, after weight loss and regain in  47 obese men and women who lost 12kg (weight stable) and 9kg (weight regainers) in a study by Bosy-Westphal et al. from 2013

"In addition, the effect of weight loss and weight regain over a longer follow-up period of 6 months had been studied in 47 obese males and females (Bosy-Westphal. 2013). There were considerable differences between weight-reduced/weight-stable individuals compared with weight regainers. Over a period of 6 months, weight-reduced/weight-stable individuals had lost 12 kg body weight, the weight change-associated changes in the REEm - REEc values were 33 and 45 kcal/day, with initial weight loss and with long-term follow-up (i.e. between 12 weeks and 6 months). By contrast, weight regainers regained 6.3 kg body weight after an initial loss of about 9 kg. The corresponding data on the weight changeassociated changes in the REEm - REEc values were 69 and 10 kcal/day, respectively. Individual data for the group ‘regainers’ at basal before and after weight loss, as well after weight regain, are shown in [figure 2]. The changes in the REEm- REEc values argue for changes in specific metabolic rates with weight changes." (Müller. 2013b)

What? Ok, I have to admit that this paragraph from Müller's 2013 review of the literature is not actually easy to understand. So let's take a look at the data in figure 2 again. The main message here is that the weight loss narrows the natural spectrum of REEs down to the minimal requirements of your organs. In other words, the body is running on low fumes and is thus particularly prone to weight regain which can - but does not have to - lead to an increase in the per pound organ weight energy expenditure that would then become obvious in the form of a larger difference between the measured (REEm) and calculated (REEc) resting energy expenditure (green and red circles in figure 2). With the pre-post weight regain difference being 69 vs. 10, it is yet unfortunately more common that the initial organ energy expenditure is not being restored (red circle in figure 2) and the energy expenditure remains low although people regain a lot if not all of their weight.

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Suggested read: "Do Chronic Energy Deficits Make Athletes Fat? The Longer & More Severe You Starve, the Fatter You Are. Irrespective of What the Calories-in-VS-Calories-Out Formula May Say" | read more

What can you do with this information? Not that much, I have to admit. If anything the major contribution of non-muscle tissue to the diet induced reduction of the resting metabolic rate should remind you that it may be at least equally important to spare the mass of the organs in your splachnic bed as it is to maintain as much lean muscle tissue as possible when your dieting.

I don't know if you remember the recent study about citrulline and it's effect on the maintenance of muscle and visceral tissue mass (see figure 1 in the respective article) or previous SuppVersity posts on other non-essential amino acids, such as glutamine or arginine? All of them are primarily "organ food" and an adequate provision of these conditionally essential amino acids should be considered as important as the provision of the purportedly muscle-protecting BCAAs if you want to keep the loss of organ mass at a minimum and your resting metabolic rate up. Whether and how you can influence the individual metabolic rate, of these organs is yet a totally different question to which no one has found a definitive answer, yet.

References:

• Bosy-Westphal A, Kossel E, Goele K,et al. Contribution of individual organ mass loss to weight-loss associated decline in resting energy expenditure. Am J Clin Nutr 2009; 90:993–1001.
• Bosy-Westphal A, Schautz B, Lagerpusch M,et al.Effect of weight loss and regain on adipose tissue distribution, composition of lean mass and resting energy expenditure in young overweight and obese adults. Int J Obes 2013.
• Elia M. Organ and tissue contribution to metabolic rate. In: Kinney J, Tucker HN, editors. Energy metabolism: tissue determinants and cellular corollaries. New York: Raven Press; 1992. pp. 61–79
• Müller MJ, Bosy-Westphal A. Adaptive thermogenesis with weight loss in humans. Obesity 2013a; 21:218–228.
• Müller MJ, Wang Z, Heymsfield SB, Schautz B, Bosy-Westphal A. Advances in the understanding of specific metabolic rates of major organs and tissues in humans. Curr Opin Clin Nutr Metab Care. 2013b Sep;16(5):501-8.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure. Am J Clin Nutr 2010; 92:1369–1377.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Evaluation of specific metabolic rates of major organs and tissues: comparison between men and women. Am J Hum Biol 2011; 23:333–338.
• Wang Z, Ying Z, Bosy-Westphal A,et al.Evaluation of specific metabolic rates of major organs and tissues: comparison between nonobese and obese women. Obesity 2012; 20:95–100.

Electrolyte Supplement Blocks Exercise Induced Elevations in LDH, Urea, Leucocyte Infiltration into the Heart & the Congestion of Renal Blood Vessels

For the average gymrat it is probably not a question of life or death, but an increase in recovery due to a decrease in detrimental muscle damage in response to dehydration should be an very good argument to get some salt and glucose in after / around your workouts.

Electrolytes have been at the heart of several SuppVersity articles as of late (check them out). Few of them did however have a direct link to exercise. Reason enough to discuss the results of a pertinent paper that was published by two scientists from Cairo University (Osman. 2013). At first sight, the study Hala F. Osman and  Azza M. Atya conducted does not appear to be very exciting. After all, the effects of electrolyte supplements on re-hydration after a workout are nothing that would not have been analyzed in previous studies. Moreover, the study at hand, which has been published in the latest issue of the World of Applied Sciences Journal, is a rodent study and the results would actually be pretty boring if the poor critters had not been sacrificed right after a lengthy HIIT session comprising 5x4 min intervals at 25m/min with 2min break in between, in order to beyond the conventional blood analyses and take a look at their hearts and kidneys.

Rodents don't complain

Now based on human studies we already know what happens in the blood, when we exercise vigorously, CK rises, LDH rises, the serum electrolyte levels get messed up, etc.

Figure 1: Changes in serum electrolyte levels (chloride, magnesium, calcium, phoporus, potassium, natrium) after the HIIT-esque workout w/ or w/out electrolyte supplementation (Osman. 2013)

The exercise induced changes in the electrolyte levels Osman & Atya observed in the rodents were in fact very similar to those that have been reported in human studies. What's more important, though is the fact that they persisted only those rats that did not receive the Rehydran-N solution daily for 45 days + immediately after the workout (see figure 1).

"[...] sodium ions decreased significantly  (P 0.05) after exercised while after  supplementation  by  Rehydran-n  and  Rehydran-n+ (Mg+Ca) citrate in group III and IV the level of sodium ion restored near to the control value. While  potassium ions level increased significantly (P 0.05) in exercised group. The supplementation by Rehydran-n and Rehydran  n+ (Mg+Ca) citrate in group III and IV not affected on the level of potassium and not return the value near to control value." (Osman. 2013)

One thing that is at odds with previous research in humans, is the acute -18.6% drop in magnesium levels. Interestingly, this drop was blunted even when the rodents received the magnesium free NaCl + K electrolyte supplement. The immediate provision of magnesium in the Rehydran-n + Mg + Ca arm of the study, on the other hand, raised the Mg2+ levels by +18% and did thus also result in a transient electrolyte imbalance.

Rehydration prevents organ stress

As I already hinted at in the introduction, having slightly screwed electrolyte levels, as well as elevated amounts of creatine kinase, lactate dehydrogenase and urea in the blood are more or less negligible problems compared to any direct ill health effects the dehydration and the corresponding loss of electrolytes could have on the structural integrity and health of your heart and kidneys. Effects such as those Osman and Atya saw when they analyzed the organs of the animals who did not compensate for the electrolyte loss by the immediate provision of adequate amounts of salt after a workout:

Figure 2: Sections of heart tissue after the workout (Osman. 2013)

"Figure [2] microscopic sections of heart from exercised group [2b] showed leucocytic cells infiltration in cardiac myocytes. Whereas other sections from Rehydran-n treatment  group [2c]  revealed  few  focal intermuscular  inflammatory  cells  infiltration.  While  Rehydran-n+  (Mg+Ca)citrate  treatment  group [2d] showing  no  histopathological  changeslike  those  in control group [2a]." (Osman. 2013)

Kidney sections of rat from control group revealed no histopathological changes. While in  prolonged exercising group showing hyalinosis [=degeneration] of  glomerular tufts. Moreover in Rehydran-n group vacuolations of epithelial lining renal tubules [=accumulation of waste that will be flushed out later on]. Rehydran  n+ (Mg+Ca) citrate treatment group congestion of renal blood vessel was observed [=one reason the better stick to salt, only].

Now, these results certainly sound more frightening than they actually are. Our bodies are (just like those of rodents, by the way) well equipped to handle the occasional cell / organ damage. And the heart is - believe it or not - "only" a muscle. It works slightly different, but can take at least as much beatings as our skeletal muscle tissue. Beatings of which the creatine kinase (CK) and lactate dehydrogenase (LDH) levels in the supplemented groups clearly show that they are are ameliorated by the the provision of electrolytes.

Figure 3: Creatine kinase (CPK), lactate dehydrogenase (LDH) and urea elevations (in %) after 5x4min treadmill runs with 2 min rest in-between (Osman. 2013)

"The present results are in accordance with the exhausted exercised rats resulted in an increased growth in serum CPK activity. This increase, however was markedly reduced in the rats after administration of antioxidant. For instance, 16h exercise in rats caused a marked rise in  activity levels of serum LDH. Increase in serum LDH  activity is mainly due to release from heart and skeletal muscles into blood stream. [...] Different  types  of  stressors  cause  an  increase in activities of serum creatine phosphokinase and lactate dehydrogenase in humans and animals which is an indication of tissue damage." (Osman. 2013)

Now you may be asking yourselves, whether similar effects can be expected in human beings!? Well, the answer should be obvious: "Similar", yes. 100% identical, no. Maughn et al., for example, demonstrated similar (re-)hydration benefits in human subjects in the 1994 - it should be obvious thought that they refrained from cutting their subjects open and checking what happened to their hearts so that we can only speculate about the extend of cellular / structural damage and the corresponding compensatory effects in humans.

Table 1: Ingredients of a single sachet of Rehydran-N which was bought by the reaserchers at a local pharmacy - no sponsorship involved

What can be said for with some certainty, though, is that it is unlikely that you would need more than one sachet of the electrolyte formula with its 0.3g K, 0.7g NaCl, 0.58g tri-sodium citrate and 4g glucose to achieve similar effects. After all, Osman & Atya modeled the amount of electrolytes the rodents received to what human beings would get from one serving of Rehydran-N. It is thus for once not necessary to calculate a human equivalent dose of the electrolytes in the water of the lab animals.

No glucose no effective rehydration

What is however necessary is the inclusion of the sugar or rather glucose in the rehydration formula, because the latter increases the efficacy of the formula significantly.

"The discovery that sodium transport and glucose transport are coupled in the small intestine so that glucose accelerates absorption of solute and water was potentially the most important medical advance this century."(Anonymous in Lancet. 1978)

So don't skip on the miniscule amount of glucose - even if you are suffering from carbophobia and believe that any amount of carbohydrates is going to make you hold water. Trust me, if anything will make you hold water its their absence and the suboptimal uptake of the electrolytes in the absence of glucose that will make you look like a watery version of the Michelin Man.

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NaHCO3 loading increases performance & decrease LDH activity.

Bottom line: Despite the fact that they may have been derived in a rodent study, the results Osman and Atya present in their most recent paper re-emphasis the need for adequate (re-)hydration before, during and even more so after workouts. In the vicinity of a workout, the latter is best achieved, using a simple salt + glucose mixture that can, but does not necessarily have to include ~360mg magnesium- and ~800mg calcium-citrate. You should yet keep in mind that the the increased levels of Mg2+ and Ca2+ can become burden on your kidney, although they appear to have beneficial effects on the heart (see figure 2).

And as far as the ostensibly beneficial decrease in LDH in the Rehydran-N + Mg + Ca group is concerned, this may well be a simple result of the alkalizing effect of magnesium and calcium ions. Assuming this is correct, similar benefits should occur in response to sodium bicarbonate, aka baking soda supplementation (learn more). The latter is after all part of the standard anti-rhabdomyolysis (=rapid breakdown of damaged skeletal muscle tissue) protocol where it does prevent both, further damage to the musculature and permanent damage to the kidneys (Vanholder. 2000).

References: 

• Anonymous. Water with sugar and salt. Lancet. 1978 Aug 5;2(8084):300-1.
• Maughan RJ, Owen JH, Shirreffs SM, Leiper JB. Post-exercise rehydration in man: effects of electrolyte addition to ingested fluids. Eur J. Appl. Physiol. Occup Physiol., 69: 209-15.
• Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol. 2000 Aug;11(8):1553-61. Review.

On Short Notice: EPO Reduces Mitochondrial Biogenesis, Excess Zinc Raises BP + Impairs Insulin Clearance, ALA + UDCA "Cure" NAFDL, Earthing, Estrogen & Your Heart ...

Image 1: 2h of earthing would certainly solve this problem just as they seem to reduce the risk of developing blood clots,  by the way (see below)

I thought I could try something new today and just give you a brief research update on stuff that would otherwise not necessarily make it to the SuppVersity, because it is not really worth writing a whole blogpost on it. Please make sure you let me know whether or not you like this format. I am open to comments of all sorts and suggestions on whether to continue posting things like this; on the respective frequency; on whether or not you want stuff in more detail and so on and so forth... You know that I am writing this blog for no-one else, but YOU, so take this chance and give me some feedback to allow me to tailor things even more to your demands. But enough of that, let's get to the studies for today :-)

EPO treatment reduces mitochondrial biogenesis...

...in  fast twitch-muscle fibers, only! Vladimir E. Martinez-Bello and his colleagues from Spain and France (yeah, the Tour de France has just begun ;-) have found that after no more than 3-weeks of thrice weekly subcutaneous administration of 300IU of rHuEpo, the expression of PGC-1α, mTFA and cytochrome c in the fast-twitch muscles of the gastrocnemius were significantly reduced (Martinez-Bello. 2012).

Figure 1: Changes in haemoglobin, haematocrit, and reticulocytes (colored large graph) and expression of enzymes involved in the mitochondrial biogenesis pathway in gastrocnemius muscle (black-and-white small graph) before and after 21 days of rHuEpo or saline administration (Martinez-Bello.2012)

If you take a look at figure 1 you could certainly argue that this is a simple consequence of the increase in haemoglobin, haematocrit and the rediculocyte count and the subsequently increased oxygen delivery to the target muscle. Unfortunately, that does not really make sense, since that should be all the more important for the highly oxygen-depended slow twitch muscles in the soleus, where the expression of neither of the three enzymes changed. So, as Martinez-Bello et al. say "further studies are needed to address and clarify this issue as well as to establish accurate biological mechanisms". This may also explain the fact that the treatment did not ellicit any changes in maximal aerobic performance, something you would actually expect as a mechanistic consequence of the EPO-induced increase in oxygen transport.

Too much zinc can increase blood pressure by compromising kidney function 

You already know that the long-term ingestion of high doses of zinc can set you up for insulin resistance and diabetes (cf. "Zinc: 15mg Are Plenty - After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome"). According to another recent study from the Health Science Center, Saitama Medical University in Japan (Kasai. 2012), excessive zinc intake can reduce renal function and thus indirectly elevate in blood pressure.

Figure 2: As you can see, the compromised kindey function did not just lead to profound increases in blood pressure, it also reduced the insulin clearance by >20% and > 40% (based on Kasai. 2012)

And if you take a closer look at the effects the diets that contained 10x (for humans 10x above normal is "only" 150mg/day, something I have in face seen as a recommendation for "natural testosterone bosting" on some of the boards) and 40x the normal amount had on insulin clearance within after no more than 4-weeks, it becomes clear that in addition to the previously mentioned increased nutrient absorption the inability to clear insulin from the blood may have been an additional factor which contributed to the progression of insulin resistance, Tenaja et al. observed in their study (see "Zinc: 15mg Are Plenty"; Taneja. 2012)

400mg of ALA + 300mg of UDCA + diet = good bye NAFLD

Pretty impressive data comes from a recent human trial on non-pharmacological interventions in patients with non-alcoholic fatty liver disease (Gianturco. 2012). As the data in figure 3 goes to show the combined effects of a colorically reduced diet (1,200kcal/day for women, 1,500kcal/day for men) with a macronutrient ratio of 26% fat (5% polyunsaturated, 14% monounsaturated, and 7% saturated), 25% protein, and 49 % carbohydrates, 400mg of alpha lipoic acid (ALA) and 300mg of ursodeoxycholic acid, a bile acid that is also known as ursodiol, led to profound  improvements in all markers of non-alcoholic fatty liver disease.

Figure 3: Changes in characteristic markers of liver health after 12 months on a hypocaloric diet with and without supplementation of ALA and/or UDCA (Gianturco. 2012)

What is particularly remarkable, though, is the fact that these pronounced improvement took place in the absence of significant weight loss changes in blood glucose, insulin, HOMA-IR or triglycerides. In other words: It was not a side effect of improved weight loss, increased insulin sensitivity or the restoration of a healthy fatty acid metabolism. And what's best about all it: The treatment was side effect free!

On ultra-short notice

Image 2: It may be debatable whether or not running around in the dark is the ideal form of aerobic exercise, in terms of it's effects on your hemoglobin, platelet, etc. counts it does yet not make a difference when you train.

• Your blood does not mind, when you train - Time of the day has no effect on impact of maximal aerobic exercise on haematological parameters (hemoglobin, platelets, erythrocytes, and leukocytes) immediately after, and two hours after the exercise (Shahidi. 2012)
• "Earthing" could help reduce blood clotting - A "groundbreaking" *rofl* study by Chevalier et al. reveals that 2h of sitting quietly in a room grounded with conductive patches on the soles of your feet and palms of their hands (patches must be connected to stainless-steel rod inserted in the earth outdoors) you can reduce the zeta potential (charge of your red blood cells) and thus reduce their potential to form blood clots (Chevalier. 2012)
• Sunscreen from within? Coffee could hold the answer! - Although this is exclusively based on epidemiological data, it's interesting that Song et al. report that an increased caffeine intake appears to protect to against Basal cell carcinoma of the skin (Song. 2012). Men and women who consumed more than 3 cups/d had the lowest risk (10% and 21% lower than people who consumed only 1 cup or less). And while caffeine from other dietary sources (tea, cola, and chocolate) had similar effects, there were no benefits associated with the consumption of decaffeinated coffee.
• Estrogens protect against cardiac hypertrophy - If you are a friend of OTC or pharmacological estrogen eradication, you should be aware that the results of a recent study from the University of Colorado suggest that estrogen has preventive effects against pathological hypertrophy of the heart (Haines. 2012). And while this could explain why some of the non-aromatising anabolic steroids have more pronounced cardiovascular side-effects it should be mentioned that the study was conducted on female aromatase knockout mice and does therefore not necessarily translate 1:1 to humans, let alone men... the 2x increase in cardiac hypertrophy, on the other hand, is so pronounced that I would think twice whether or not it really is necessary to rid yourself from as much estrogen as possible, after all it appears to play an important role in skeletal muscle growth and repair, as well - see "Intermittent Thoughts on Building Muscle: Estrogen, Friend or Foe of Skeletal Muscle Hypertrophy?"

References:

1. Chevalier G, Sinatra ST, Oschman JL, Delany RM. Earthing (Grounding) the Human Body Reduces Blood Viscosity-a Major Factor in Cardiovascular Disease. J Altern Complement Med. 2012 Jul 3.
2. Gianturco Y, Troisi G, Bellomo A, Bernardini S, D’Ottavio E, Formosa V, Lo Iacono C, Verrusio W, Marigliano B, Marigliano, V. Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety . Hepatol Int. 2012 Jul 3.
3. Haines C, Harvey P, Leinwand LA. Estrogens Mediate Cardiac Hypertrophy in a Stimulus-Dependent Manner. Endocrinology. 2012 Jul 3.
4. Martinez-Bello VE, Sanchis-Gomar F, Romagnoli M, Derbre F, Gomez-Cabrera MC, Viña J. Three weeks of erythropoietin treatment hampers skeletal muscle mitochondrial biogenesis in rats. J Physiol Biochem. 2012 May 25.
5. Kasai M, Miyazaki T, Takenaka T, Yanagisawa H, Suzuki H. Excessive Zinc Intake Increases Systemic Blood Pressure and Reduces Renal Blood Flow via Kidney Angiotensin II in Rats. Biol Trace Elem Res. 2012 Jul 4.
6. Shahidi F, Alhosseini SLN, Kandi YNMP.  The Effect of a Maximal Aerobic Exercise Session in the Morning and Afternoon on Certain Hematological Factors in Young Athletes. Annals of Biological Research, 2012, 3 (6):2703-2707
7. Song F, Qureshi AA, Han J. Increased caffeine intake is associated with reduced risk of Basal cell carcinoma of the skin. Cancer Res. 2012 Jul 1;72(13):3282-9.
8. Taneja SK, Jain M, Mandal R, Megha K. Excessive zinc in diet induces leptin resistance in Wistar rat through increased uptake of nutrients at intestinal level. J Trace Elem Med Biol. 2012 Jun 8.

Red Meat and Even Pork is Good for You!? Reduced Weight Gain, Improved Insulin Sensitivity and No Adverse Side Effects from "Red Meat Supplementation" Even in Rodents!

Image 1: Must be the red meat between those healthy grain based burger buns that makes this rodent fat, right? What? Yeah... of course epidemiologists count this as a "red meat meal" - it has "red meat" in it... wait, ah yeah: More likely pink slime, with some totally benign ammonia in it, you are right ;-)

Those of you who have been around here at the SuppVersity for some time, may have remembered the "Additional(!) 200g of Pork a Day Build Lean Mass, Improve Blood Lipids & Glucose Levels" from September 2011, when a couple of weeks ago yet another "anti-meat study" hit mainstream media news. You will probably have read enough of the certainly accurate, but in a way pointless criticism of the study, elsewhere in the bloggosphere, so that I decided not to repeat the argumentation, which basically discards the value of all epidemiological data (as long as it is not interpreted in accordance with the respective blogger ;-)... now, not all scientists are epidemiologists, some, like Petzke et al. (see the post I mentioned before) or, more recently Haiyan Chen and his (or her?) Chinese co-workers actually care to conduct experiments on the health effects of red meat consumption and their results are by no means as unequivocal (Chen. 2012), as the introductions and dead-certain conclusions of the epidemiologist would suggest.

If you want to lose weight and ward off diabesity, you "supplement" with red meat!

In their 24 week trial, Chen et al. kept a group of 24 male Wistar rats, who had been pre-fattened on the standard SAD-like "high fat diet" for 14 weeks (an interesting side note: only 24 of the 46 rats who received the HFD diet got actually obese, i.e. they gained +20% more body-fat than their peers - so what does that tell you about the "general" fattening effect of the "high fat diet"?) on either

• regular rodent chow with 67.8% of energy from carbohydrates, 12.8% fat and 19.4% protein, or
• red-meat enriched "high" protein diets with 46.6% of energy from carbohydrates, 16.7% fat and 36.7% protein

The "high protein" (I am putting the term "high" between inverted commas, because I am well aware that for many of you the "medical high protein diet" contains about the least imaginable amount of protein you believe you could get along with; suggested read "20g or 40g of Whey? That is NOT the Question!") contained 780g of lean pork powder per kg. With the other components from the standard chow being added at ratios that would make sure that the rodents from both groups would have an identical caloric intake of 336 kJ/day (=normal caloric intake for adult rats). In the course of the 24-week study period (for rodents with their 2-3 year life expectancy this is like 10-15 human years!), the scientists measured the body weight and fasting  blood glucose levels weekly and every 4 weeks, respectively.

Figure 1: Body weight (in g) during and visceral fat (in g) after 24 weeks on high protein meat or normal protein chow diets (data adapted from Chen. 2012)

As you can see in figure 1 the addition of the "unhealthy red meat" (remember: neither was this "healthy chicken" nor grass-fed beef, but Chinese pork meat - similar to the lean cuts of pork that made the women in the Petzke study lean out and build muscle) reduced the weight gain of the already obese 17-week old rodents by more -57% (!) and left them with 44% less of pro-inflammatory visceral fat mass than their peers on the healthy "meat-less" standard chow. Despite an increase in BUN, the creatinine levels of both groups were identical and there were no signs of kidney damage in any of the rodents kept on the meat-supplemented high protein diet.

Figure 2: Insulin AUC during intravenous glucose tolerance test (IGGT) and fasting GLP-1 levels
(data adapted from Chen. 2012)

The insulin response during an intravenous glucose tolerance test (a measure of insulin resistance), on the other hand, was reduced, just as fasting GLP-1 levels were (P < 0.05; for more information on the intricate relationship between GLP-1, insulin and obesity / fat loss, check out my previous post on WMHDP).

Why the different results? Don't tell me meat is not bad for me!

Aside from the questionnaire based epidemiological studies, where "Pizza Salami" is a "red meat food", I mentioned earlier, there definitely is experimental data (on which the working hypothesis of many of the epidemiological studies are founded, by the way) that would suggest that feeding red meat to rodents is not the best thing to do... now, if we discard species-specific issues for the time being, how can those differences be explained? Chen et al. provide a pretty straight-forward set of potential confounding factors in their discussion, which I am going to summarize for you:

• meat is an energetically denser protein source than dairy - this may explain why, compared to dairy products, meat has been found to be positively associated with weight gain in rats (eg. Belobrajdic. 2003)
• the longer experimental duration - in previous studies there were already "tendencyies toweight loss" at the end of the mostly 10-12 week study periods 
• the age of the animals may have a profound effect on the weight gain; for rats that are younger than the ones in the study at hand, an increased weight could would in fact indicate a healthy effect during the most active growth period of the rodents rats; this would not preclude, though that the same diet would facilitate weight loss in mature rats

Still, aside from the lack of blood lipid profiles, blood calcium and phosphorus levels, which as the scientists concede would have been "important [to judge the] safety of the high-protein diet", there is another factor, I would really insist on, if it had not been for the repeatedly mentioned human trial by the German scientists and that would be that the use clenbuterol, salbutamol and sibutramine - "weight loss adjuvants", or the Chinese would probably say dietary supplements to ensure lean livestock *rofl* - is still daily fare in China, so that - theoretically speaking - we cannot exclude that the rodents received a whopping dose of any, if not all of these drugs in their "meat-supplemented" high protein diets ;-)

High Protein Diets, Acid Load, Calcium Loss, Osteoporosis and a 50% Increase in Diabetes Risk - Is There a Link?

Shouldn't it be obvious that the "happy medium" must be the solution, when high protein leads to brittle bones, and low protein to frail muscle? Sure! But where is this "happy medium"?

Some of you may remember my recent Facebook post "High Protein Diet in the Firing Line. Rodent Study Says: Kidneys Are at Risk". It was based on a press release you could read on all the major science-news outlets on the Internet; a press release that will give the average reader the impression that the corresponding study by Aparicio et al. would "prove" that high protein diets will ruin your kidneys and eventually jeopardize your health (read more).

Another paper (Cao. 2014), Jose Antonio, the CEO of the ISSN and the editor of the ISSN's journal posted on Facebook yesterday, didn't get as much media attention, though.

No wonder, the message of this study is after all not in line with one of the fundamental arguments you will hear, whenever you question the allegedly necessary restriction of total protein intake to 0.8g/kg, maximally 1.2g/kg protein per kilogram body weight day in the current nutritional guidelines:

"[...S]hort-term consumption of high-protein diets does not disrupt calcium homeostasis and is not detrimental to skeletal integrity."

That's not what you will learn at med-school and it is certainly not in line with the hysteria about protein intakes that are 2x or even 3x higher than the 0.8g protein per kilogram body weight we are supposed to consume. Apropos RDA, the subjects in the control group of the said study by Jay J Cao et al. consumed a diet that contained exactly those 0.8g/kg body weight that's supposed to be good for us. The 21 human guinea pigs in the treatment groups, on the other hand, consumed 2x and 3x more than the average dietitian would recommend and they did so for 31 days (Cao. 2014).

Figure 1: Protein intake (in g/day; left), mineral intake (in mg/day; middle)  and calculated renal acid load (in mEq; right) of 49 normal weight, healthy men (n=32) and women (n=7) who consumed normal (0.8g/day), high (1.6g/kg per day) and very high protein (2.4g/kg per day) energy restricted (40%) diets for 4 weeks (Cao 2014)

If you take a look at the PRAL values in Figure 1, you can see that math (not bio- or physiology!) tells us that this reckless practice could compromises the acid-base balance of the healthy, normal-weight subjects, whose energy restricted diets were modeled on the increasingly popular high protein weight loss diets.

Equations vs. experiments | PRAL vs. urinary calclium loss | theory vs. practive

The urinary analysis the scientists conducted does yet speak a very different language. There is, as the scientists emphasize in the discussion of the results no evidence that

Suppversity Suggested Read: "High protein diet = high protein loss" | more

"habitual consumption of dietary protein at levels above the RDA [would] significantly alter urinary calcium excretion, dietary calcium retention, or markers of bone turnover or BMD, despite increased urinary acidity. These results indicate that diets that are 2 or 3 times the RDA for protein are not detrimental to calcium homeostasis when calcium and vitamin D are consumed at recommended intake"

In that I would like to emphasis the importance of adequate calcium (min. 800mg/day) and vitamin D intakes (800-1000IU/day) and the fallacy of the word "habitual". The study at hand did not test the effects of "habitual" high protein consumption. It tested the effects of short-term (28 days) high protein consumption in a low calorie scenario, which is by definition less prone to produce adverse inflammatory and thus potentially pro-osteoporotic side effects (Mundy. 2007).

Not eating enough protein could increase bone loss, when you're dieting

In view of the fact that the evidence I am about to cite, stems from rodent model of postmenopausal bone metabolism, I deliberately used the word could in the headline of this paragraph. And still, the way in which the low protein diet  "negatively impacted bone mass and magnified the detrimental effects of vitD and/or estrogen deficiencies" (Marotte. 2013) in the pertinent study from the Buenos Aires University is particularly disturbing.

High dietary acid load increases diabetes risk by more than 50%: In spite of the fact that this is neither bone- nor kidney-specific, the 56% increase in diabetes risk scientists from the Gustave Roussy Institute in France report in their latest paper in Diabetology, for the 16,621 subjects with PRAL values of only 7 mEq/day is so impressive that I simply had to include it in this article. Specifically in view of the fact that a brief glimpse at the food intake of the subjects in the figure to the left will suffice to see that protein is by no means the only "acid" offender in the SAD diet.

The (postmenopausal) women the scientists try to model with their ovariectomized rats (=rats whose ovaries have been removes) are after all one of the many patient groups who are advised to carefully control their protein intake to make sure that the additional acid load will not compromise their bone health even further and that in spite of the fact that there is ample evidence that the current RDA for protein is inadequate to maintain optimal health, particularly when the total energy intake is restricted and especially in populations who are susceptible to bone loss (Kerstetter. 2005; Chernoff. 2004).

Figure 2: We know for quite some time not that low protein diets decrease the absorp- tion of protein (Kerstteter. 2005). It's not certain if this is "just" a homeastatic me- chanism to stabilize the net/acid balance.

In their 2005 study, Kerstetter et al. were in fact able to show that protein intakes that are 2.6x higher than the RDA increase the effective absorption of calcium from the diet (see Figure 2).

This increase stands in contrast to the significant decrease in calcium absorption the researchers observed in the healthy young (age: 26y) women in the low protein arm (0.7g protein per kg body weight) of the study and should remind us that a reduction in protein intake is not going to stop the insidious loss of bone that's caused by the triage of low estrogen, no exercise and a diet that may be low in protein, but high in acid producing grains (Remer. 1995) and devoid of alkaline fruit and vegetables.

I could now go more into details, but I will just leave you with the notion that the "paleo diet" is, despite its high meat content, among the most kidney-, and above all bone-friendly diets we know. In fact, its fruit and vegetables content yield a net alkaline renal load, and will lead to significant improvements in urinary calcium excretion rates (Appelet. 1997; Frassetto. 2013).   

☄ Note: If you want more about the "Paleo connection" - let me know this (best on Facebook) and what you would be most interested in and I will address that in a future SuppVersity article.

Practically speaking: The results of the Cao study tell us that you can get away with a high protein load in otherwise SAD-ly (SAD = standard American diet) normal diet in the short run. What it does not tell you is that you can keep on this kind of "just add a ton of protein to the regular junk you eat diet" with ever-increasing dietary acid loads won't hurt your kidneys, bones and pancreas (see red box) in the long run.

If you want to eat a high protein diet, that's free of kidney, bone, or general meta- bolic side effects, it will thus have to have the fruit and vegetable content of what we currently deem a "paleo diet" - a diet with a relatively high protein content, tons of vege- tables, tubers and fruit and a limited (not no!) amount of grains. This will bring your citrate, magnesium and potas- sium intake up spare calcium and help you to ward off the evermore prevalent diabesity epidemic.

Bottom line: It may be human, but still is idiotic to isolate any single macronutrient as "the reason" for osteoporosis and bone loss. Looking exclusively at what we could potentially be doing wrong is not going to help us here. Rather than that, we should look at what we can be doing right - in other words, what should we eat, if we want to maintain not just bone-, kindey-health, but also muscle- and metabolic health (note: protein alone won't help you maintain muscle mass).

If we look at the results of the previously referenced trial by Frasetto et al., in which the researchers from the University of California San Francisco, which achieved a reduction of the potential renal acid load from 28mEq (which is more than the PRAL of 7mEq that's associated with a >50% diabetes risk; see red box) to -96 mEq on a diets that differed not in macronutrient, but in food, and consequently micronutrient-, specifically mineral-content, you will be hard pressed to keep the deabte on the short-sighted  "carbohydrates are good, protein is bad and fat is the devil, anyways"-level it is currently on.

We should be talking about food, instead. Not just about "more fruit and vegetables", but also about what you will necessarily have to skip for them, if you want your diet to work: Highly processed foods, including meats(!), sodas and other sweetened drinks, white bread, candy, chips, etc. It's not that you can't ever eat any of those, but as long as any of these items is on your list of foods you eat on a daily basis, there is still room for improvement.

References

• Aparicio, V. A., et al. "High-protein diets and renal status in rats." Nutrición hospitalaria: Organo oficial de la Sociedad española de nutrición parenteral y enteral 28.1 (2013): 232-237.
• Appel, Lawrence J., et al. "A clinical trial of the effects of dietary patterns on blood pressure." New England Journal of Medicine 336.16 (1997): 1117-1124. 
• Cao, Jay J., et al. "Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized controlled trial." The American journal of clinical nutrition 99.2 (2014): 400-407.
• Chernoff, Ronni. "Protein and older adults." Journal of the American College of Nutrition 23.sup6 (2004): 627S-630S. 
• Frassetto, L. A., et al. "Established dietary estimates of net acid production do not predict measured net acid excretion in patients with Type 2 diabetes on Paleolithic–Hunter–Gatherer-type diets." European journal of clinical nutrition 67.9 (2013): 899-903.
• Kerstetter, Jane E., et al. "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women." Journal of Clinical Endocrinology & Metabolism 90.1 (2005): 26-31.
• Mundy, Gregory R. "Osteoporosis and inflammation." Nutrition reviews 65.s3 (2007): S147-S151.
• Remer, Thomas, and Friedrich Manz. "Potential renal acid load of foods and its influence on urine pH." Journal of the American Dietetic Association 95.7 (1995): 791-797.

Let There Be Light: 10 New Studies to Enlighten You About the Health Effects of Light Exposure on Health & Physique

No, the sun does not kill you. If you control your exposure it may extend your life and improve your life-quality significantly.

It's about time to "let there be light" to illuminate the benefits of regular well-timed exposure to sunlight and it's short frequency component. Only recently, researchers from the Japanese National Institute of Advanced Industrial Science and Technology (AIST) were able to show that daytime light exposure has significant beneficial effects on cognitive brain activity. Significant enough to have the subjects perform better on an oddball task and to significantly increase cortical activity related to cognitive processes (Okamoto. 2014).

But is that really all, bright light, or more specifically, the regular and well-timed exposure to bright light can do for you?

The effects on circadian rhythm could be behind the Sun's anti-cancer effects

Sunlight, Bluelight, Backlight and Your Clock

Sunlight a La Carte: "Hack" Your Rhythm

Breaking the Fast to Synchronize the Clock

Fasting (Re-)Sets the Peripheral Clock

Vitamin A & Caffeine Set the Clock

Pre-Workout Supps Could Ruin Your Sleep

Certainly not. I mean if it's ill-timed, like the evening use of light-emitting eReaders it will negatively affect your sleep, mess up your circadian rhythm and decrease your alertness on the next morning. Similar results, i.e. drowsiness and suppression of energy metabolism the following morning, have been reported by other studies, as well (Kayaba. 2014).

As a SuppVersity reader you do yet know all about those negative effects from the circadian rhythm series, anyway. Reason enough for me, to focus primarily on all the good stuff, the well-timed exposure to bright light can do for you in today's Special of the SuppVersity Short News.

• If you can't let go off your mobile at night, use blue blocker glasses as a countermeasure for alerting effects of evening light-emitting diode screen exposure - According to researchers from the Psychiatric Hospital of the University of Basel, blue blocker glasses (BB) significantly attenuate LED-induced melatonin suppression in the evening and decrease vigilant attention and subjective alertness before bedtime.
  
  Strangely, though, visually scored sleep stages and behavioral measures collected the morning after were not modified. Still, van der Lely et al. conclude: "BB glasses may be useful in adolescents as a countermeasure for alerting effects induced by light exposure through LED screens and therefore potentially impede the negative effects modern lighting imposes on circadian physiology in the evening "(van der Lely. 2014).
• UV-light protects against "brainflammation" in MS model - Scientists from the University of Wisconsin-Madison report in their latest paper that UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis.
  
  Previous studies have already shown that UV radiation (UVR) can suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple-sclerosis (MS), independent of vitamin D production. The mechanism of this suppression did yet remain to be elucidated, until Wang et al. (2014) observed that UVR (10kJ/m²) does not just inhibit the inflammation and demyelination of the spinal cord, but will also dramatically and significantly reduce spinal cord chemokine CCL5 mRNA and protein levels.
  
  In conjunction with an increased production of intereron-gamma (IFN-γ) and IL-10, which are actually used to treat all sorts of autoimmune diseases, artificial and natural UV light can thus actually "prevent the migration of inflammatory cells into the CNS" (Wang. 2014).

• 

  Melatonin conc. after 4 days w/ dim vs. bright light and tryptophan rich vs. poor breakfast (Fukushige. 2014).

  Bright light in the AM and the consumption of a breakfast that's high in tryptophan can help you maintain a healthy circadian rhythm - In case you are asking yourself how you can grasp all the benefits that are associated with having an intact circadian rhythm, you may be intrigued to hear that researchers from the Fukuoka Women's University have been able to show that an increase in tryptophan intake at breakfast combined with daytime light exposure has beneficial effects on melatonin secretion and sleep quality. As you can see in the figure to the left it will significantly elevate the evening melatonin peak, which is critical for an optimal circadian rhythm.
  
  If you are looking to optimize your internal clock bright light (either sunlight or a 10,000 Lux daylight lamp) + tryptophan (seeds, nuts, soy, cheese, chicken, turkey, fish, oats, beans and eggs are the TOP10 sources) are the way to go. If you want an extra "kick" add some coffee to the equation. This will increase the light responsiveness of the circadian pacemaker - well, at least in mice it does (Diepen. 2014).

If you want to design your own "dawn simulator" that's the spectrum you need (Virginie. 2014).

Wanna be smarter, but can't get enough sleep? Start your day with a dawn simulation: Chronic sleep restriction (SR) has deleterious effects on cognitive performance that can be counteracted by light exposure. Scientists from the Psychiatric Hospital of the University of Basel have recently been able tho show that a dawn simulating in the AM will increase your task performance throughout the day after morning; and what's best: The benefit was most pronounced in those participants who sucked the most when they didn't get a good night's sleep (Virginie. 2014).

• Bright lights at work will keep you sane, happy and alert - If you are working in an insufficiently lit office without natural sunlight, you should be prepared to develop physiological, sleep and depressive symptoms.
  
  Assuming you have a window in your office, you will get a significantly more pronounced total and peak exposure to bright light that's going to correlate with 33% reduced levels of the stress hormone cortisol, a more natural rhythm of melatonin and a reduced risk of minor psychiatric disorders and depressive symptoms (MA) in the evening.
  
  That's at least what the results of a recent study from the UFRGS in Porto Alegre indicates (Harb. 2014). A study the authors of which proudly say that their "study demonstrated that not only may light pollution affect human physiology but also lack of exposure to natural light is related to high levels of cortisol and lower levels of melatonin at night, and these, in turn, are related to depressive symptoms and poor quality of sleep" (Harb. 2014).

• 

  If you want to light up the darkness, when it's actually time to sleep do it with green (555nm) or red, not blue light, which suppresses melatonin (Bonmati-Carrion. 2014).

  Staying away from nightly night exposure may also help to keep your arteries clean even in the old age - Studies indicate that even after  adjustment for confounding factors, including age, gender, body mass index, current smoking status, hypertension, diabetes, dyslipidemia, sleep medication, estimated glomerular filtration rate, nocturia, bedtime, duration in bed (scotoperiod), day length (photoperiod), urinary 6-sulfatoxymelatonin excretion and daytime and nighttime physical activity, exposure to light at night is associated with carotid intima-media thickness (Obayashi. 2014).
  
  If you don't want to develop subclinical carotid atherosclerosis, when you are old, it would thus be a good idea to adhere to the basic rules of sleep hygiene: a dark room and/or blindfolds will keep your arteries clean and may thus save your life ;-)
• If you have kidney problems, get out in the sun if you want to survive - Scientists from the University of California Irvine Medical Center were able to show that dialysis patients residing in higher UV index regions have lower all-cause mortality compared to those living in moderate-high UV regions (Shapiro. 2014).
  
  More specifically, the ~60year-old subjects residing in moderate-high UV index regions had a 16% reduced risk of all-cause mortality. Those living in very-high UV index regions had a 1% higher risk reduction (17%). Interestingly, there was a similar inverse association between UV index and mortality was observed across all subgroups, but it was more pronounced among whites vs. non-whites.
• Wear those shades (or bluelight blocker glasses) before any important sport event - Why? Stupid question. If you dabble around with your smartphone "unprotected" the evening before an important sport event for only 30 minutes, this can influence exercise performance under hot conditions during the subsequent early morning (Thompson. 2014).

Even brief light exposure, when your eyes are closed messes with your circadian rhythm.

Pah, when your eyes are closed, light is not a problem, right? Wrong. Even ,illisecond flashes of light phase delay the human circadian clock during sleep. While a greater number of matched subjects and more research will be necessary to ascertain whether these light flashes affect sleep, data from a recent study from the California Mental Illness Research Education and Clinical Center suggest that 2-msec light flashes given every 30 sec have an effect on the circadian rhythm of healthy volunteers. And while Zeitzer et al. (2014) tried to use the flashes to modify the rhythm in a beneficial way, the exact opposite can also be the case. It all depends on how / when you are exposed to light when you sleep.

Sleep disturbance and adaptive immunity. Following a night of sleep loss, or during a period of sleep disturbance, nerve fibers from the sympathetic nervous system (SNS) release the neurotransmitter norepinephrine into primary and secondary lymphoid organs and stimulate the adrenal gland to release stored epinephrine into systemic circulation. Both neuromediators stimulate leukocyte adrenergic receptors (e.g., ADRB2) and activate nuclear factor (NF)-κB-mediated inflammatory programs (Irwin. 2015).

• If your grandparent's have Alzheimer's install a timer-based light system - This may not just increase their sleep quality, but it will also improve their behavior and mood as indicated by reduced depression scores on the Cornell Scale for Depression in Dementia and agitation scores from the Cohen-Mansfield Agitation Inventory (Figueiro. 2014).
  
  I must warn you, though: The recent field study from the Rensselaer Polytechnic Institute is promising, but the results should be replicated using a larger sample size and perhaps using longer treatment duration.
• If you have to work night shifts consider using 1-5mg melatonin 1h before you go to bed - Why? You have to counter the natural decline in melatonin production that occurs over consecutive days of night work (Dumont. 2014).
  
  In a recent study from the Sacre-Coeur Hospital of Montreal the melatonin production of the healthy volunteers decreased progressively decreased over consecutive days of simulated night work, both during nighttime and over the 24 h. Interestingly, this decrease was larger in women using oral contraceptives and independent of bright light exposure.
• Get out into the sun and cure your back pain - If your back hurts and neither you or your doctor have a clue why, try getting into the sun. A study from the UMIT in Austria shows that only three sessions in front of 5.000 lx lamp improved the depressive symptoms and reduced the pain intensity in CNBP adults with chronic nonspecific back pain (Leichtfried. 2014).

One of the side effects of blue light LED exposure (open circles) in the PM is a sign., but practically prob. irrelevant reduction in energy exp. on the next morning (Kayaba. 2014).

Bottom line: I really hope that I do not have to sum up the results for you. I mean, it should be obvious that sleep hygiene at night and light exposure at day are among the most important factors of the lifestyle-factors in the exercise + nutriton + lifestyle solution to perfect health & obesity protection (Partonen. 2014).

Against that background I would like to use the last lines to put another emphasis on the results of the recent study by Kayaba et al. (2014) which found that one of the negative consequences smartphone junkies have to suffer on the morning after using their devices before bed is a reduction in energy expenditure.

If you take a look at the data in the figure at the right (open circles = exposed; full circles = non-exposed), you will yet realize that this probably isn't the worst side effect of blue-LED light exposure in the evening. The reduction is significant in the AM, yes, but on its own it's not practically relevant | Comment on Facebook!

References:

• Bonmati-Carrion, Maria Angeles, et al. "Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure." International Journal of Molecular Sciences 15.12 (2014): 23448-23500.
• Diepen, Hester C., et al. "Caffeine increases light responsiveness of the mouse circadian pacemaker." European Journal of Neuroscience 40.10 (2014): 3504-3511.
• Dumont, Marie, and Jean Paquet. "Progressive decrease of melatonin production over consecutive days of simulated night work." Chronobiology international 0 (2014): 1-8.
• Figueiro, Mariana G., et al. "Tailored lighting intervention improves measures of sleep, depression, and agitation in persons with Alzheimer’s disease and related dementia living in long-term care facilities." Clinical interventions in aging 9 (2014): 1527.
• Fukushige, Haruna, et al. "Effects of tryptophan-rich breakfast and light exposure during the daytime on melatonin secretion at night." breast cancer 4 (2014): 9.
• Harb, Francine, Maria Paz Hidalgo, and Betina Martau. "Lack of exposure to natural light in the workspace is associated with physiological, sleep and depressive symptoms." Chronobiology international 0 (2014): 1-8. 
• Irwin Michael, R. "Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective." Annual Review of Psychology 66 (2015): 143-172.
• Kayaba, Momoko, et al. "The effect of nocturnal blue light exposure from light-emitting diodes on wakefulness and energy metabolism the following morning." Environmental health and preventive medicine 19.5 (2014): 354-361. 
• Leichtfried, Veronika, et al. "Short‐Term Effects of Bright Light Therapy in Adults with Chronic Nonspecific Back Pain: A Randomized Controlled Trial." Pain Medicine 15.12 (2014): 2003-2012.
• Obayashi, Kenji, Keigo Saeki, and Norio Kurumatani. "Light exposure at night is associated with subclinical carotid atherosclerosis in the general elderly population: The HEIJO-KYO cohort." Chronobiology international 0 (2014): 1-8.
• Okamoto, Yosuke, and Seiji Nakagawa. "Effects of daytime light exposure on cognitive brain activity as measured by the ERP P300." Physiology & behavior 138 (2015): 313-318.
• Partonen, Timo. "Obesity= physical activity+ dietary intake+ sleep stages+ light exposure." Annals of medicine 46.5 (2014): 245-246.
• Shapiro, Bryan B., et al. "The Relationship Between Ultraviolet Light Exposure and Mortality in Dialysis Patients." American journal of nephrology 40.3 (2014): 224-232. 
• Thompson, A., et al. "The Effects of Evening Bright Light Exposure on Subsequent Morning Exercise Performance." International journal of sports medicine EFirst (2014).
• van der Lely, Stéphanie, et al. "Blue blocker glasses as a countermeasure for alerting effects of evening light-emitting diode screen exposure in male teenagers." Journal of Adolescent Health (2014).
• Virginie, Gabel, et al. "Dawn simulation light impacts on different cognitive domains under sleep restriction." Behavioural Brain Research (2014).
• Wang, et al. "UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis." Arch Biochem Biophys. (2014). [Epub ahead of print]
• Zeitzer, Jamie M., et al. "Millisecond Flashes of Light Phase Delay the Human Circadian Clock during Sleep." Journal of biological rhythms (2014): 0748730414546532.

Three Reasons Why Your Doctor May Falsely Believe Your Kidney, Liver or Heart Were Damaged If You Get Blood Work Done Without Adequate Rest After Intense Workouts

Sometimes lab values are deceiving - specifically if allegedly pathological elevations of kidney, liver and (heart) muscle enzmes are a perfectly physiological reaction to exercise. 

You already know reason #1. The heavily increased creatine kinase (CK) levels I've discussed in a previous article at length may look exactly as if you were about to have a kidney failure.

In fact, the CK-levels can be elevated more than 100-fold after an intense workout (Pettersson. 2008). Accordingly, Mougios, et al. (2007) attempted to develop revised reference values for athletes in their 2007 study. The scientists' test revealed that CK levels of >1000 IU/L in male and 513 IU/L in female athletes would be better cut off levels for athletes who are still training than the regular upper limit of <208 IU/L.

If you want to avoid muscle damage, you may try BFR and hypoxia training.

BFR, Cortisol & GH Responses

BFR - Where are we now?

Hypoxia + HIIT = Win?

BFR for Injured Athletes

Strength ⇧ | Size ⇩ w/ BFR

Training & Living in Hypoxia

Closely related to the CK-levels, which are unquestionably the #1 reason your doctor may want to call an ambulance, despite the fact that all you're suffering from is heavy deep onset muscle soreness, are elevated transaminase levels (see time course of elevation in the Petterson study).

Figure 1: Changes in serum enzyme levels after exercise in trained and untrained subjects in response to 15 minutes treadmill running and an 8k run (Fowler. 1962).

In medicine, the presence of elevated transaminases, commonly the transaminases alanine transaminase (ALT) and aspartate transaminase (AST), are considered to be an indicator of liver damage. In athletes, however, elevated levels of both of these enzymes are - just like elevated creatine kinase levels - a mere sign of exercise induced muscle damage.

As the data from a 1962 study by Fowler, et al. indicates, even 15 minutes on a treadmill can lead to significantly elevated ALT (back in the day the enzyme was still called "GPT") and AST ("GOT") levels. An 8k run can increase ALT and AST by more than 150% (see Figure 1). In that the extent of ALT & AST elevations probably depends on the individuals' susceptibility to exercise induced protein breakdown, which is the actual reason the enzymes which breakdown the protein debris in the liver are elevated.

As it is the case with the creatine kinase enyzmes, many primary physicians and scientists are unaware of the connection and the long-lasting elevations of serum transaminases in response to hard workouts.

Figure 2: In trained marines AST (=SGOT), ALT (=SGPT) react significantly less pronounced (Schlang. 1961)

Against that background it's hardly surprising that Pertusi et al. report in a 2007 paper that the exercise-induced elevations of aminotransferases is also the reason that anabolic steroid induced liver damage has overreported. An overreporting of which the scientists say that is has "in turn, biased physicians against considering muscle damage as a possible cause for aminotransferase elevations (Pertusi. 2001).

Chronically elevated liver enzymes should still not be taken lightly. Even if they don't indicate liver damage, they could be a sign of chronic overtraining. After all, Hunter et al. (1971) were able to show that training reduces the initially exuberant increases of the aminotransferases significantly.

Speaking of not taking lightly, one thing you shouldn't take lightly either is your doctor's suspicion that you may have developed a heart disease. 

More specifically, Elliott and La Gerche have recently been reporting that strenuous endurance exercise (SEE) is associated with acute depression of RV systolic function, thus suggesting that exposure to repeated bouts of SEE can have potential long-term consequences. La Gerche and Claessen argued that left atrial pressure is increased during SEE, thereby increasing pulmonary artery pressure. As Fabian Sanchis-Gomar et al. point out in an editorial comment, they thus stated

"that frequent episodes of increased RV work induced by long-term SEE can promote compensatory RV remodeling, increase myocardial damage biomarkers such as troponins and B-type natriuretic peptide, or even accelerate heart failure (HF)" (Sanchis-Gomar. 2015). 

The Spanish researchers do yet highlight that to the best of their knowledge the bulk of the evidence available supports that the above mentioned alterations which include among other the cardiac-specific creatine kinase marker are rather transient, with a dose-effect relationship existing for exercise intensity and duration.

"Physicians and health professionals should be aware that healthy individuals who engage in SEE sport events could exhibit acute, transient cardiological features that are apparently compatible with cardiac diseases, yet these alterations are attributable in most cases to transient physiological responses rather than pathological status"(Sanchis-Gomar. 2015).

Against that background, it may be a good idea to take two weeks off in order to retest, if your doctor says that your biomarkers suggest that you may be suffering from heart disease.

Read the previous article for all the details on CK elevations.

Bottom line: While you should never take the "bad news" your doctor may have for you lightly. It may be wise to evaluate, whether allegedly pathological changes in creatine kinase (CK), transaminases (ALT & AST) and / or strange alterations in troponins and or B-type natriuretic peptide that suggest you may be suffering from kidney, liver or heart damage may simply be the result of a recent workout.

Since CK, ALT and AST can remain elevated for more than a week (see time course of elevation of AST in Petterson's study), it would be best to take two weeks off of strenuous training before you do a re-test which will then - hopefully - confirm that the disconcerting abnormalities were nothing but a result of your last intense workout | Comment on Facebook!

References:

• Elliott, Adrian D., and Andre La Gerche. "The right ventricle following prolonged endurance exercise: are we overlooking the more important side of the heart? A meta-analysis." British journal of sports medicine (2014): bjsports-2014.
• Fowler, William M., et al. "Changes in serum enzyme levels after exercise in trained and untrained subjects." Journal of applied physiology 17.6 (1962): 943-946.
• Hunter, J. BARRY, and JERRY B. Critz. "Effect of training on plasma enzyme levels in man." Journal of applied physiology 31.1 (1971): 20-23.
• Mougios V. Reference intervals for serum creatine kinase in athletes. Br J Sports Med. 2007 Oct;41(10):674-8. Epub 2007 May 25.
• Pertusi, Raymond., R. D. Dickerman, and W. J. McConathy. "Evaluation of aminotransferase elevations in a bodybuilder using anabolic steroids: hepatitis or rhabdomyolysis?." JOURNAL-AMERICAN OSTEOPATHIC ASSOCIATION 101.7 (2001): 391-394.
• Pettersson, Jonas, et al. "Muscular exercise can cause highly pathological liver function tests in healthy men." British journal of clinical pharmacology 65.2 (2008): 253-259.
• Sanchis-Gomar, Fabian, et al. "Long-term strenuous endurance exercise and the right ventricle: Is it a real matter of concern?." Canadian Journal of Cardiology (2015).
• Schlang, Captain HA, and C. A. Kirkpatrick. "The effect of physical exercise on serum transaminase." The American journal of the medical sciences 242.3 (1961): 338-341.