Removal of Amalgam Fillings Associated With Reductions in Memory Loss, Fatigue, Anxiety, Confusion & Other Health Problems, Observational Study from Canda Shows

Amalgam removed = health restored?

While there is little doubt that mercury vapor poses a known health risk, there is neither a clearly established safe level of exposure, nor evidence that similar ill health effects can occur with chronic low grade exposure to mercury vapor from dental amalgam fillings.

As you may know amalgam is not 100% but "only" 50% mercury, but is that enough to represent a significant health risk? The objective of a recent study from the University of Calgary was "to determine if mercury exposure from amalgam fillings is associated with risk of adverse health effects" (Zwicker. 2014).

Mercury is among the reasons fish should not be your exclusive protein source

Salmon Better Than Whey?

Cod protein for recovery

Krill = Super Protein?

Farmed vs. Wild-Caught Fish

Fast vs. slow protein

5x More Than FDA Allows

To this ends, Zwicker et al. conducted a large longitudinal non-blinded study involving participants from a preventative health program in Calgary, Canada. The goal was to assess whether (a) there was an association between having amalgam fillings, the amount of mercury in the urine and reported health issues and (b) whether the 14 previously self-reported health symptoms would improve in a sample of persons who had their fillings removed compared to a sample of persons who had not had their fillings removed.

Figure 1: Summary data for study sample with urine mercury measures (Zwicker. 2014)

A brief glimpse at the baseline data reveals that the presence of 18.4 and 23.7 amalgam fillings on the tooth surfaces of the subjects in the treatment (amalgam fillings will be removed) and the amalgam control group (amalgam fillings will not be removed) have higher amounts of mercury in their urine.

What do previous studies say? Oskarsson et al. (1996) fount that mercury from amalgam fillings was the main source of mercury in milk. In fact, the amount of mercury babies were exposed to from breast milk ranged up to 0.3 μg/kg/d, of which approximately one-half was inorganic mercury and which corresponds to approximately one-half the tolerable daily intake for adults recommended by the World Health Organization (Oskarsson. 1996). Other studies present opposing results, though, and claim that fish, not amalgam fillings was the major source of mercury in breast milk (Drexler. 1998). Still, evidence from other studies, such as Nylander (1987), which report mercury vapor from amalgam fillings to be the major source of mercury in the organs of human subjects, support the notion that at least the "first generation" amalgam fillings are a major source of human mercury exposure. The correlation with subjective health symptoms, on the other hand, is less obvious. Studies like Ahlqwist et al. (1988) and a twin study by Björkman et al (1996) clearly refute the existence of a significant correlation.

What is interesting, but not actually what the scientists wanted to investigate is the fact that the mercury levels in women are generally higher (may be a result of a comparatively lower body size and mass and similar mercury exposure).

What do you think happened one year after the fillings were removed?

Well, let's see. As the data in Figure 2 indicates, the mercury levels in both amalgam groups declined in comparison to the baseline measure (follow up data for the amalgam free group is not available)

Figure 2: Changes in mean urinary mercury level after one year after the amalgam fillings
were removed / not removed (Zwicker. 2014)

The effects are, I guess you will agree with me on that one, not exactly impressive. Against that background the obvious question is: "Are the self-reported measured improvements in headache, memory loss, depression, fatigue, anxiety & co a result of a placebo effect?" I mean, the subjects obviously knew that their amalgam fillings were removed (remember: it's a non-blinded study!) and you bet that they've read some of the horror stories about mercury on the Internet.

Table 1: One year odds of symptom improvement and worsening in the group of subjects who had the amalgam fillings removed, controlled for age and sex | Odds ratio coefficients are the odds of change in treatment group relative to the positive amalgam group. {P values}; * indicates coefficient is different from 1 at size 0.05; ^ represents statistical significance at size 0.10 (Zwicker. 2014).

So, can we tell whether the "improvements" you see in Table 1 are actually brought about by the removal of the amalgam fillings or simply by the subjects psyche? I would say we can't and that's why I have my doubts about the validity of the researchers conclusion that "that mercury exposure from amalgam fillings adversely impact health and therefore are a health risk" (Zwicker. 2014) - not necessarily because I believe they are harmless, but rather because the data the scientists evaluated does not prove this claim.

If avoiding mercury from fish is a good thing, avoiding mercury exposure from amalgam fillings is a good thing, too. Irrespective of the fact that the study at hand provides only insufficient evidence of its ill health effects.

Bottom line: I personally had my one filling removed back in the day, but rather the necessary result of the fact that it was in a baby tooth ;-)

That being said, I still subscribe to the researchers assertion that "a safer alternative materials for dental fillings should be encouraged to avoid the increased risk of health deterioration associated with unnecessary exposure to mercury" (Zwicker. 2014), yet not because of the data in the study at hand, though, but rather based on the notion that you would want to limit any unnecessary exposure to heavy metals, no matter how small the amount that's leeching from the amalgam fillings may be, though.

On a side note: A study investigating the commonly heard claim that the removal of amalgam would only increase the load of mercury (at least temporarily) indicates that - if it's done properly - "[t]he uptake of amalgam mercury in the GI tract in conjunction with removal of amalgam fillings seems to be low" (Björkman. 1997). So if you are considering this procedure, it's unlikely that it will make whatever symptoms you believe to have as a consequence of having amalgam fillings more severe | Comment on Facebook!

References:

• Ahlqwist, Margareta, et al. "Number of amalgam tooth fillings in relation to subjectively experienced symptoms in a study of Swedish women." Community dentistry and oral epidemiology 16.4 (1988): 227-231. 
• Björkman, Lars, Nancy L. Pedersen, and Paul Lichtenstein. "Physical and mental health related to dental amalgam fillings in Swedish twins." Community dentistry and oral epidemiology 24.4 (1996): 260-267.
• Drexler, Hans, and Karl-Heinz Schaller. "The mercury concentration in breast milk resulting from amalgam fillings and dietary habits." Environmental research 77.2 (1998): 124-129. 
• Oskarsson, Agneta, et al. "Total and inorganic mercury in breast milk and blood in relation to fish consumption and amalgam fillings in lactating women." Archives of Environmental Health: An International Journal 51.3 (1996): 234-241.
• Nylander, Magnus, Lars Friberg, and Birger Lind. "Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings." Swedish dental journal 11.5 (1986): 179-187.
• Zwicker, Jennifer D., Daniel J. Dutton, and John Charles Emery. "Longitudinal analysis of the association between removal of dental amalgam, urine mercury and 14 self-reported health symptoms." Environmental Health 13.1 (2014): 95.

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. 2012)

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. 2012).

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 .2012)

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. 2012)

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. 2012)

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. 2012).

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. 2012). 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. 2012).

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. 2012)

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. 2012)

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. 2012), 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. 2012)

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. 2012 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. 2012 Sep 27. 
• de Lisio M, Parise G. Characterization of the Effects of Exercise Training on Hematopoietic Stem Cell Quantity and Function. J Appl Physiol. 2012 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. 2012 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. 2012 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, 2012.
• Raichlen DA, Foster AD, Seillier A, Giuffrida A, Gerdeman GL. Exercise-induced endocannabinoid signaling is modulated by intensity. Eur J Appl Physiol. 2012 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. 2012 Sep 19.

Circadian Rhythmicity - Sunlight a La Carte: How to "Hack" Your Circadian Rhythm With 30min of Light Therapy Per Day

Image 1: The last installment was all about avoiding artificial  light, today we will use it to our advantage.

In the last installment of the SuppVersity Circadian Rhythm Series, we have taken a brief look at some of the physical aspects of light, in general, and how they relate to the physiological effects sunlight and artificial light exert on our biological clock. We have identified the omnipresence of unnatural "light" (in the broadest sense)  in our 24/7 x 365 world as one of the, if not the most important reason that our natural circadian rhythm and all the metabolic and endocrine parameters that depend on it got out of balance and we have discussed a couple of things that could be useful for anyone to either regain or retain the natural rhythm our genes have evolved with. In today's installment we are now (figuratively) turning back the time and take a look at the beneficial effects the same light(s) that keep(s) us awake, when we are long supposed to sleep, can have on the accuracy of our biological clock, earlier in the day.

Let the sun shine in your eyes to feel it in your heart ;-)

Now, that the day's are long and the sun is up or at least about to rise, when we are making our way to the bathroom to shower, brush our teeth, brew our coffee and grab something to eat (or continue our fast) before we pour ourselves into our daily business, many of you may already have forgotten those dark winter days, when you leave the house in darkness and sit in the office all day and are happy to see the last rays of the sun, when you jump into your car and head home, to the gym or to wherever you may be going on an "afternoon", your body can hardly distinguish from the darkest night.

Image 2: Selected physiological functions and their circadian pattern (Richter. 2011).

Scientists have long coined a specific term for this syndrome: Seasonal affective (SAD). Despite the fact that SAD has become more or less synonymous with the dreaded "winter blues", however, the depressive mood many people experience during the winter months, may be the most prominent, but certainly ain't the only symptom of a whole set of pathologies that are directly or indirectly related to a mismatch between your biological and social clocks. Against the background that the former controls a whole host of very important physiological processes (see image 2), it stands to reason that the consequences of this mismatch are not restricted to psychological problems. Moreover,  the number of patients and non-patients, i.e. people who simply regard symptoms such as...

• sleep problems - oversleeping but not refreshed, cannot get out of bed, napping in the afternoon
• overeating - carbohydrate craving leading to weight gain
• depression, despair, misery, guilt, anxiety - normal tasks become frustratingly difficult
• family / social problems - avoiding company, irritability, loss of libido, feeling emotionally 'numb'
• lethargy - too tired to cope, everything an effort
• physical symptoms - often joint pain or stomach problems, lowered resistance to infection
• behavioral problems - especially in young people

as part of their nature, for whom the occurrence of these problems is still seasonal, is constantly declining, so that what began as "seasonal affective disorder" has long lost both, its restriction to "affect" and its "season-"ality. A phenomenon, by the way, which should hardly surprise us. After all, we have done our very best to get rid of all kinds of all the inconvenient and unproductive seasonality in our lives, so that cynics would probable argue, that we are now paying the price for the 24/7 + 365-days-a-year availability of everything... 

From seasonal affective to circadian affective and physiological disorders

Before we are digressing any further into philosophical consideration, let's take a more scientific 2nd look at the enlightening (all puns intended) connection between the "winter blues", obviously a matter of circannual rhythmicity, and its high(er)-frequency equivalent the 'daily affective disorder'.

Figure 1: Circadian and circannual rhythm are both influenced by the sunlight and insufficient light exposure in the "high in intensity light hours" of the summer days can have the same detrimental effects on your psychological and physiological well-being as the dreaded "winter blues" aka "seasonal effective disorders" - no wonder they also respond to the same treatment strategies, i.e. dawn simulations and / or bright light therapy (respective data from Terman. 2006.)

The collage of data and illustrations I have come up with in figure 1 should actually make it pretty obvious: Despite the fact that the term 'circadian affective and physiological disorders' I have already used in the caption of this paragraph does not exist, the symptoms by which it makes itself felt, the sleep problems, the ravenousness, the depressive undertone, the lethargy, the tiredness, etc. are virtually identical.

Figure 2: Illustration of normal circadian rhythmicity (green), in seasonal affective disorders (SAD, red) and a circadian mismatch due to a phase-shift (violet); the units are more or less arbitrary.

In the end, you could probably argue that "SAD" is nothing but the "natural" accumulation of a light debt and results in a similar suppression of the natural amplitude (= degree of ups and downs, figure 2, green) of the circadian rhythm as a mismatch of the internal clock with external time emitters, above all the light of the sun.

How to "hack" your circadian rhythm

Despite the fact that the outcome of seasonal depressive disorders, on the one hand, and the downstream effects of permanent "social jet lag", or other misalignments of your biological clock and the "social time" you are living in, on the other hand, are in fact almost identical, the classic "winter blues" is the result of simple light deprivation, while the more complex pattern of circadian disorders has an intensity and a phase component and will necessarily have to be fixed differently.

What chronotype am I? Find out and become a part of a scientific study! While it is unquestionably possible to come up with an indefinite number of "classes" between the classic "early bird" (=person who raises with or before sun rise) and the "owl" (=person who rises, when the birds are having lunch), the scientific branch of chronotyping, which is occupied with the study of human rhythms in behavioral and cognitive functions, has come up with (you guessed it) a standardized questionnaire, the "Munich Chronotype Questionnaire", you can fill out here and will receive a "personal profil" via email.

Figure 4: Suggested starting times for 10,000-lux 30-minute session; timepoint is ~8.5h after the estimated melatonin onset (Termann. 2005)

If you don't want to wait or don't trust the German researchers, you can also download the modified Horne-Östberg Questionnaire, here. When you've filled it out, you will be able to calculate your "Morningness Eveningness Score." Based on that score you can then locate your suggested starting time in figure 4. The respective recommendations are based on a paper by Terman from 2005 and have been developed for SAD, so take them as what they are guidelines, not rules!

While research suggests that the correct timing of light exposure/therapy is of little or no importance as far as its beneficial effects on depression scores are concerned (Wirz-Justice. 1993), the so-called "circadian phase-delay", as scientists refer to the "time-shift" between natural and social clock (see figure 2, violet), must not be ignored if you intend to realign or protect yourself from future misalignment of your social and biological time domains.

The situation in figure 2 (violet), for example, depicts a ~4h phase shift, which would get you up and out of bed with the dreaded "2-AM wake-up call" (by the way pretty common in people who overtrain), 4h before your time!  

Now what can you do to battle this problem? Get out of bed switch on your 10,000 lux light therapy lamp, log on to facebook, check a couple of emails and sip a strong coffee? If you want to and can afford to be back to bed at 6 PM, go for it. If you don't you better stay in bed (and in the dark!), get up as you would "like" to and take a 30min "light shower" 1-2h after the time your morningness-eveningness score   would dictate (see infobox "What chronotype am I?") This will help you to push the onset of melatonin release gradually backwards until you reach the point, where it is ~8.5h before your "optimal" or necessary wake-up time.

For someone with an MEQ score of 45 who would ideally get up at 7 AM but won't make it to the office in time if he isn't up at least 1h "before his current time", on the other hand, a different strategy would be necessary.

Instead of turning around and sleeping the day away, he would set the alarm clock ahead by about 1h, jump out of bed at 5:00 AM, get his 30 min of bright light therapy in front of his 10,000 Lux lamp and do his regular morning routine afterwards. As soon as it becomes easier to get out of bed, it's time to set the alarm clock to 5:30 AM and eventually to 6:00AM.

It should be obvious, that even that will never be optimal for someone who is a born owl, i.e. a person whose genetic clock is set to wake him up, when the rest of the world has just had lunch. The daily and most importantly regular, early and intense light exposure in the morning is  going to help him to get out of bed easier and it will also increase his chances that the earlier onset of melatonin production combined with the tricks I have outlined in the last installment of this series allow him to fall asleep in time and get his 7-9h of sleep before the next light therapy session.

Warning: Guidelines and examples are no blueprints! These examples, as well as the figures in the infobox on chronotypes are very broad recommendations! You won't be able to avoid experimenting in order to pinpoint the optimal regimen for you.

Ok, I am convinced, what device shall I get?

What's that Valkee device? Is that any good? While there is a sponsored study on the efficiacy of the Valkee bright light device a "plug in your ear" light therapy device, the study is uncontrolled, which renders is more or less impossible to say how much of the observed beneficial effect the scientists measured by two different tests (HAMD-17 & BDI-21) were simply the result of a placebo effect (Timonen. 2012).

Figure 3: Comparison of BDI improvements of the Valkee device and classic light therapy (based on Timonen. 2012 and Meesters. 1993, respectively)

This does not mean that this device does not work, it just means that light therapy through the eyes is a well-established method not just to treat depressive disorders, but also to reprogram your circadian rhythm. The Valkee, on the other hand, could be a mobile and thus very convenient alternative (or adjunct) to the classic devices. It does yet still lack credible independent research that would prove its effectiveness - something like the 1993(!) study by Meesters et al. I picked as a comparison and in which only 4 days of light therapy with a classic 10,000 lux lamp had slightly more pronounced effects than the Valkee, even 10 days after the therapy had ended (see figure 3; note: It must be said that this is at best a binary comparison, because a quantitative comparison of the study outcomes from these studies can would at best serve as a basis for a hypothesis that would then have to be verified in a future trial).

The information we have compiled in the just mentioned last installment of this series does also come very handy, when you are clicking through the various product descriptions that will turn up when you enter the search token "light therapy lamp" into your favorite product search engine. Basically there are two different systems you can use if you want to try to "hack" (I know that this term is ludicrous, but I'll use it anyway, 'cause its also fashionable and would boost the sales if I ever intended to make an ebook out of this text ;-):

• a 10,000 lux full natural daylight spectrum white energy lamp or light therapy device, which will provide the full natural spectrum (you remember that's the sum of all frequency components of the sunlight, see  figure 2 in the last installment) without the potentially carcinogenic UV part - I don't have to tell you that this implies that you won't get tanned, right?
• a blue light that produces a light that has the same spectral composition as the blue sky on a summer day and is likewise devoid of the invisible high frequency ultraviolet part of the spectrum

According to the claims of the producers of such devices the blue light allows for shorter exposure times to achieve the desired effects.

This assumption does unquestionably seem reasonable, but the same is true for the hilarious notion that eating more protein will make you gain proportionally more muscle or that the presence of cholesterol in arterial plaque would verify that cholesterol is the cause of heart disease. Independent and controlled large(r) scale trials to support these claims are yet scarce and in the case of an even more innovative device, the fancy Valkee "brain stimulation set" that's supposed to shine light through your ears onto the recently discovered light sensitive proteins in your brain (for more info on the Valkee, check out the infobox on the right and the website of the producer), simply non-existent.

I personally did therefore decide to buy a classic white energy light system, also in view of the fact that you can simply place it right next to you at the breakfast table, the newspaper, your computer screen or wherever you want during your morning "circadian rhythm hacking sessions" *rofl* - this is by the way I use my device - at least if the weather / season / my wake-up time doesn't allow me to use the sun instead; and believe me, the blue light or Valkee could hardly be more convenient.

Side effects, summary & guide:

Bright light therapy guide

Intensity & wavelength requirements For white light pick a device that emits the full-spectrum of the visible light at 10,000 lux (measured at the level of the eyes of the user!)

Distance from light source Remain positioned at approximately 20–60 cm from the light source; don't stare directly into the light, the lamp just has to be in your field of view

Time of day for application In 90% of the cases the morning is the best time to apply light therapy; different rules do apply if you have to adapt your biological clock to a totally unnatural social rhythm, as it would for example be the case if you work night-shifts.

Dose 30 min at 10,000 lux, more does not necessarily help more, if you feel sleepy too early rather implement a second sitting

Onset of effect and maintenance 3–7 days till the effect sets in; if you use it to enforce an unnatural rhythm the effect will probably vanish shortly after discontinuation of therapy

In case of non-response double-dose, if you feel sleepy before your time; start earlier or add melatonin (3-10mg) before bed, if you can't get to bed in time.

In the end, it is still up to you, which device you want to buy. The guidelines in the overview on the right, which is based will probably work for the blue light systems and the Valkee, as well (assuming that those do work ;-). It is yet still by no means sure if and to which extend you can benefit and there are even occasional reports of allegedly mostly transient side effects, such as...

• hyperactivation and/or difficulty to fall asleep, which is by the way not just restricted to cases in which you apply the light too late in the day
• light headaches and/or nausea, which are particularly likely to occur in the transition periods or can be a simple consequence of starting starting out with a too hefty (=long) dose
• visual side effects, which are usually a result of staring into the light, which is not necessary for the light therapy to work, so don't do it

Other than that, Terman & Terman mention in a 2005 review paper that in their trials on patients with all sorts of serious psychological disorders, like manic depression or bipolar disorders, it was often necessary to increase the dosages, both time- and intensity-wise slowly to avoid flare-ups of these pre-existing problems. Compared to your average energy drink, let alone pill, the 30-min in front of a light therapy lamp are yet still child's play... its effects on the other hand are longer lasting and way more far-reaching.

A sneak peak on the next installment: In the next installment of the Circadian Rhythm Series we are going to leave the light out, only literally, of course, and devote ourselves to such profane things as food, what your biological clock tells you about when and what to eat and which effects this can have on your physique, performance and overall health.

References:

• Baroni BM, Leal Junior EC, Geremia JM, Diefenthaeler F, Vaz MA. Effect of light-emitting diodes therapy (LEDT) on knee extensor muscle fatigue. Photomed Laser Surg. 2010 Oct;28(5):653-8. Epub 2010 Jul 13.
• Blouin AG, Blouin JH, Iversen H, et al. Light therapy in bulimia nervosa: a double-blind, placebo controlled study. Psychiatry Res. 1996;60:1 9.
• Braun D, Sunday S, Fornari V, Halmi K. Bright light therapy decreases winter binge frequency in women with bulimia nervosa: a double-blind, placebo controlled study. Compr Psychiatry. 1999; 40:442-8.
• Howland RH. An overview of seasonal affective disorder and its treatment options. Phys Sportsmed. 2009 Dec;37(4):104-15.
• Lam RW, Goldner EM, Soplyom L, Remick RA. A controlled study of light therapy for bulimia nervosa. Am J Psychiatry. 1994;151: 744-9.
• Meesters Y, Jansen JH, Beersma DG, Bouhuys AL, van den Hoofdakker RH. Light therapy for seasonal affective disorder. The effects of timing. Br J Psychiatry. 1995 May;166(5):607-12. 
• Reiter RJ, Rosales-Corral S, Coto-Montes A, Boga JA, Tan DX, Davis JM, Konturek PC, Konturek SJ, Brzozowski T. The photoperiod, circadian regulation and chronodisruption: the requisite interplay between the suprachiasmatic nuclei and the pineal and gut melatonin. J Physiol Pharmacol. 2011 Jun;62(3):269-74.
• Terman M, Terman JS. Light therapy. In: Kryger MH, Roth T,  Dement WC, eds. Principles and Practice of Sleep Medicine. 4th  ed. Philadelphia, Penn: Elsevier; 2005:1424-1442. 
• Terman M, Terman JS. Controlled Trial of Naturalistic Dawn Simulation and Negative Air Ionization for Seasonal Affective Disorder. Am J Psychiatry. 2006; 163:12.
• Timonen M, Nissilä J, Liettu A, Jokelainen J, Jurvelin H, Aunio A, Räsänen P, Takala T. Can transcranial brain-targeted bright light treatment via ear canals be effective in relieving symptoms in seasonal affective disorder? A pilot study. Med Hypotheses. 2012 Apr;78(4):511-5.
• Wirz-Justice A, Graw P, Kräuchi K, Gisin B, Jochum A, Arendt J, Fisch HU, Buddeberg C, Pöldinger W. Light therapy in seasonal affective disorder is independent of time of day or circadian phase. Arch Gen Psychiatry. 1993 Dec;50(12):929-37. 

Magnesium Round-Up: Know If You Are Deficient, Whether You Need More, Where to Find It, How Dietary Mg Contents Changed & How Magnesium Interacts W/ Vitamin D

24%, 23% and 22% of the DV for magnesium that's what you can find in one serving of sunflower seeds (0.25cup), halibut (4oz) and a large(r) banana - now you tell me it was impossible to get your magnesium from dietary sources.

After having handled half of the Science Round-Up from Thursday yesterday, yesterday, there is still something left to serve: seconds to the seconds, if you will and probably not so "new" as the average SuppVersity news. In order not to bore you, I will yet refrain from telling you how important magnesium is and how it is involved in thousands of enzymatic reactions ... you know the whole magnesium-guru-spiel all too well, anyway. I mean, anyone doing a cursory Google search will have to conclude that there is nothing magnesium cannot cure, right?. Whatever you may suffer from, someone has already found out that it must be related to magnesium deficiency or, even more profitable, taking the wrong form of magnesium supplements.

Apropos deficiency: How do you even know you are deficient?

What sounds like a question that could be answered in one, at best two sentences turns out to be one of the root causes of the whole confusion about magnesium. Based on a standard blood test you can only exclude that your levels are (a) so high or (b) so low that you better head straight to the emergency room. Magnesium is, just as the other electrolytes, simply too important for your body to have them drop below a certain margin in which your heart works optimally. So if there is not enough magnesium around, your body will tap into tissue stores the status of which is obviously not identical to the serum levels on a standard lab test.

Table 1:The lion's share of magnesium to replete your serum levels is not coming from your red blood cells and therefore RBC levels are only a proxy and not a 100% reliable marker of total body mg status (data based on Elin. 1987)

According to Maurice J. Arnaud who wrote a review with the telling title "Update on the assessment of magnesium status" in 2008, the most reliable method to assess the whole body magnesium status would be a metabolic ward study in the course of which a so-called "loading test" would be performed, But...

"[b]alance studies are time consuming, labour intensive and need well trained staff. They are often performed in a metabolic unit and require complete urine and faecal collections; therefore it is not a method that can be applied as a routine test for the evaluation of Mg status. Loading tests are simplified balance studies where absorption is supposed not to be disturbed when Mg is given orally so that body retention is calculated from urine elimination. Mg administration during a loading test can be either oral or intravenous and it is important that the subjects have normal kidney function. Urine is collected for 24 hours following administration of the Mg load as Mg excretion by the kidney has been shown to have a circadian rhythm . Under these conditions, the loading test is supposed to be a reliable indicator of Mg status." (Arnaud. 2008)

With the erythrocyte (red blood cell) test for magnesium, there is however an alternative available, which may not be just as reliable but appears to show a relatively high correlation with whole body magnesium levels in many, but not all studies (Malon. 2004).

How likely is it that you are deficient?

Honestly, I would hope that it is unlikely, because if that is the case for someone who is not taking supplemental magnesium you can almost be sure that her or she is following a healthy whole foods diet.

Table 2: Overview of age groups with more than 5 % of intakes below the lowest recommended intake levels in 7 European countries; T, toddlers (1–3 years (both sexes)); C, children (4–10 years); Y, youth (11–17 years); A, adults (18–60 years); S, seniors (.60 years); capitals, both sexes; lower case, women only; lower case italic, men only (Mensik. 2013)

If you take a look at table 2 you will see that even the average German gets enough magnesium in his diet, irrespective of his age, and much contrary to our neighbors in the East, West and Northwest (I could not resist to mark zinc another of those purported minerals of which conventional wisdom tells you that you simply cannot get enough from your diet).

Knowing that most of you are probably Americans, I can calm you down. You are not worse than your British friends. In fact, the NHANES data from 1999-2000 suggests that the average American Caucasian and Mexican man below 50 gets enough magnesium from his food only! Unfortunately, the same cannot be said for the women, and both male and female African Americans who have trouble meeting their requirements even if one accounts for the additional magnesium from supplements (NHANES).

Magnesium and the athlete

A note on magnesium and cramps: While there is evidence that altered serum osmolality and altered serum electrolyte concentrations, notably hypochloraemia, hyponatraemia, and hypocalcaemia (=not hypomagnesaemia) can cause generalized skeletal muscle cramping at rest in specific clinical settings, "data from well-conducted prospective cohort studies show that athletes with acute EAMC are not hyponatraemic, hypochloraemic, or hypocalcaemic and do not have an abnormal serum osmolality." (Schwellnus. 2008).

For the average athlete, a low magnesium intake is yet rather the exception and can even be problematic for athletes with a high anaerobic-to-aerobic ratio who suffer from increases in blood mg due to an overall reduction on blood volume after intense workouts, anyway (Cordova. 1992; Joborn. 1985; Monteiro. 2005; Monteiro. 2006). It is thus no wonder that not magnesium deficiencies, but high magensium levels are a problem that is commonly observed in athletes. I mean, what are you supposed to do, when even your mother "lies" to you about cramps being caused by magnesium deficiency?

"The most common alterations were higher serum phosphate (29/61, 47%) and magnesium concentrations (28/61, 46%). Abnormalities of serum phosphorus and magnesium concentrations were detected in almost half of the athletes. Hyperphosphataemia and hypermagnesaemia were the most common abnormalities." (Malliaropoulos. 2012)

The data Malliaropoulos et al. analyzed came from 130 elite track and field athletes (65 males and 65 females, age range 20-30 years) from the National Athletics Sports Medicine Center database in Thessaloniki, Greece. And maybe some of them were even on the proven non-ergogenic ZMA (zinc + magnesium + vitamin B6; cf. Wilborn. 2004).

So where do you get your supplemental magnesium from and how much?

I am not going to tell you to stop supplementing with magnesium if you feel that this has done you good in the past. It is after all an important mineral. What I want to remind you of is yet the fact that taking 100% of the RDA is imho the absolute maximum. Even if you don't end up with high levels due to supplementing more and don't care about wasting money, there is one thing that's commonly overlooked about human physiology and that is how the intake and excretion of nutrients are highly inter-related. In other words, if your body switches into a "get rid of magnesium" mode it is likely you are loosing other electrolytes you do not supplement in copious amounts (e.g. salt ;-), as well.

Figure 1: Plasma an bone (primary axis) as well as red blood cell (RBC; 2ndary axis(!)) content after 14 days of supplementation with identical amounts of magnesium in different organic and inorganic forms (Coudray. 2005)

As far as the best forms are concerned the number of studies comparing multiple forms to each other is limited and the inter-comparison of different studies not really legit. Therefore I have simply copied + pasted the figure that went with a previous article on the matter - as you can see, you can generally use whatever form of magnesium you want - even the cheap oxides, which worked wonders for anxiety ridden ladies in a study by De Souza et al. that was published in the Journal of Women's Health & Gender-Based Medicine in March 2000. As long as you take your magnesium supplements in reasonably low doses - the dose in the De Souza study for example was 200mg + 50mg B6 - and over a long enough period, they are going to bring your levels back up - if not sooner, then later.

Magnesium depletion of our foods

A note on topical Epsom salt from the early 20th century: While I did tell you on the show that I could not find peer-reviewed adequately powered studies on the topical absorption of magnesium in the for of mg oil or Epsom salt, I found a comment in a 1915 paper on the potential harm caused by cosmetics quite enlightening, esp. the part on the economic value of respective products, where Martin I. Wilber writes that the ability of respective products to penetrate the "unbroken skin has as yet not been demonstrated" and cautions against the sue "of the now widely advertised lotions containing magnesium sulphate or Epsom salt", of which "the latter preparations serve very well to show the gullability of that portion of the public that is desirous of improving its facial appearance. As Epsom salt, magnesium sulphate can usually be purchased for 5 cents a pound, while in the form of any one of the popular skin or wrinkle lotions it is sold at the rate of from $2 to $4 a pound." (Wilbert. 1915) You see, there were snake,... ah I mean mg oil vendors all over the place even 100 years ago ;-)

Aside from the almost cult-like worship of epsom salt baths and topical ng oils, the notion of a general depletion of mg in the foods we eat is one of the favorites among the bazillion of websites run by people who hoax you to believe they were concerned with your physical health, when all they are concerned with is their own financial health.

Figure 2: Changes in mineral content of selected food types from 1940-2002 (Thomas. 2007)

It is, as the data in figure 2 goes to show you true that the amount of magnesium in many of the foods we consume is lower these days than it was amidst WW2. The mg loss in meats, for example, is  driven by the processing, while corned beef has lost almost 50% of its "original" mg content, the amount of mg in roast beef and steaks is still the same, the one in turkey is even up by ~30% and for chicken it remained 100% stable (Thomas. 2007). It is also a very intriguing coincidence that the same websites will usually also tell you how we are all not just magnesium deficient, but also copper toxic. Strange in view of the fact that the average reduction in copper is -62% and thus >2x higher than that of magnesium.

Magnesium supplementation for special conditions

Before closing this round-up with a bottom line, I am briefly listing a couple of things related to magnesium or rather a deficiency in this important mineral that could be solved by simply upping your dietary and/or supplemental magnesium intake.

• 

  Higher vitamin D levels increase MG uptake from the gut and supplementation with VD has been shown to increase mg in obese, yet not in normal individuals (Farhanghi. 2009). On the other hand, mg has recently been found to be necessary for the production of calcitriol from 25OHD (Matsuzaki. 2013)

  anxiety - mg is the gate-keeper at the NMDA receptor and interacts with the GABA receptors; a deficiency can cause anxiety, the use of extra magnesium will yet not automatically solve the problem if you are not low to begin with
• depression - low cellular mg levels can precipitate if not cause depression(-like) symptoms, 150-300mg of magnesium glycinate or better taurinate can help (Eby. 2006)
• low vitamin D - while it is not yet sure if it helps with upping the storage form of vitamin D (25OHD), it has been recently established that magnesium is necessary for the production of calcitriol the active form of vitamin D; adequate levels of D also facilitate mg absorption very high levels of vitamin D, on the other hand, have been associated with low / imbalanced mg levels - probably due to their effects on calcium homestasis
• constant stress / burnout - initially low mg levels will lead to a hyper activity of the stress-axis within the HPTA; the constantly overtaxed CNS will then give in and you will end up totally burned out (Sartori. 2011); this state cannot be reversed by magnesium supplementation, alone, but it can aid the recovery process which is largely based on taking off of everything that stresses you

Whether or not simply eating more high magnesium foods will be enough or whether you actually have to buy supplements to work on these and other issues will also depend on whether

• you can digest / absorb it, which would be hampered due to vomiting, diarrhea, bowel resection, intestinal and biliary fistulas or hemorrhagic pancreatitis
• lose too much mg over the kidneys, due to chronic parental fluid therapy, osmotic diuiresis, hypercalcemia, diuretics, aminoglycosides, amphotericin B, pentamidine, cisplatin, cyclosporine, alcohol metabolic acidosis (ketosis, starvation, alcoholism), renal diseases, or
• suffer from endocrine disorders like primary or secondary aldosteronism, diabetes, hyperthyroidism or hyperparathyroidism

If anything of these sounds familiar, I would certainly consider testing my mg levels (erythrocyte test) before and while I was supplementing and that's not about wasting money on potentially unnecessary supplements, but much more about making sure that you actually get, absorb and retain enough magnesium.

---

Bottom line: Magnesium is certainly an important mineral, but its effects must not be seen in isolation, it should not be supplemented in copious amounts in isolation without medical indication and it may not be misunderstood as a natural pharmacological agent - it works by (a) replacing a deficiency or (b) countering an imbalance. Plus: It is not generally impossible to get your 300-400mg of magnesium from your diet.

References:

• Arnaud MJ. Update on the assessment of magnesium status. Br J Nutr. 2008 Jun;99 Suppl 3:S24-36.  
• Bohl CH, Volpe SL. Magnesium and exercise. Crit Rev Food Sci Nutr. 2002;42(6):533-63. Review.
• Cordova A. Changes on plasmatic and erythrocytic magnesium levels after high-intensity exercises in men. Physiol Behav1992; 52: 819-21.
• Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-70. 
• Elin RJ. Assessment of magnesium status. Clin Chem. 1987 Nov;33(11):1965-70. Review.
• Farhanghi MA, Mahboob S, Ostadrahimi A. Obesity induced magnesium deficiency can be treated by vitamin D supplementation. J Pak Med Assoc. 2009 Apr;59(4):258-61. 
• Joborn H, Akerstrom G, Ljunghall S. Effects of exogenous catecholamines and exercise on plasma magnesium concentrations. Clin Endocrinol (Oxf)1985; 23: 219-26; (Oxf).
• Malliaropoulos N, Tsitas K, Porfiriadou A, Papalada A, R Ames P, Del Buono A, Lippi G, Maffulli N. Blood phosphorus and magnesium levels in 130 elite track and field athletes. Asian J Sports Med. 2013 Mar;4(1):49-53.
• Malon A, Brockmann C, Fijalkowska-Morawska J, Rob P, Maj-Zurawska M. Ionized magnesium in erythrocytes--the best magnesium parameter to observe hypo- or hypermagnesemia. Clin Chim Acta. 2004 Nov;349(1-2):67-73.  
• Matsuzaki H, Katsumata S, Kajita Y, Miwa M. Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats. Magnes Res. 2013 May 1;26(2):83-6.
• Mensink GB, Fletcher R, Gurinovic M, Huybrechts I, Lafay L, Serra-Majem L, Szponar L, Tetens I, Verkaik-Kloosterman J, Baka A, Stephen AM. Mapping low intake of micronutrients across Europe. Br J Nutr. 2013 Aug;110(4):755-73.   
• Miriam C. De Souza, Ann F. Walker, Paul A. Robinson, and Kim Bolland. Journal of Women's Health & Gender-Based Medicine. March 2000, 9(2): 131-139.  
• Monteiro CP. Equilíbrio Oxirredutor: um estudo em nadadores e em não atletas, em repouso e em resposta ao exercício [PhD]. Lisboa: Faculdade de Motricidada Humana, Universidade Técnica de Lisboa, 2005.
• Monteiro CP, Santa Clara H, Raposo MF,et al. Effect of training and exercise intensity on magnesium status. In: Alpoim C, Vasconcelos Morais P, Santos MA, Cristóvão AJ,
  Centeno JA, Collery P, eds.Metal Ions in Biology and Medicine. Paris: John Libbey Eurotext, 2006: 546-52 
• Sartori SB, Whittle N, Hetzenauer A, Singewald N. Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment. Neuropharmacology. 2012 Jan;62(1):304-12. doi: 10.1016/j.neuropharm.2011.07.027. Epub 2011 Aug 4.
• Schwellnus MP. Cause of exercise associated muscle cramps (EAMC)--altered neuromuscular control, dehydration or electrolyte depletion? Br J Sports Med. 2009 Jun;43(6):401-8. 
• Thomas D. The mineral depletion of foods available to us as a nation (1940-2002)--a review of the 6th Edition of McCance and Widdowson. Nutr Health. 2007;19(1-2):21-55. Review.
• Wilbert MI. Cosmetics as Drugs: A Review of Some of the Reported Harmful Effects of the Ordinary
  Constituents of Widely Used Cosmetics. Public Health Reports. 1896-1970; 30(42): Oct. 15, 1915. 3059-3066.
• Wilborn CD, Kerksick CM, Campbell BI, Taylor LW, Marcello BM, Rasmussen CJ, Greenwood MC, Almada A, Kreider RB. Effects of Zinc Magnesium Aspartate (ZMA) Supplementation on Training Adaptations and Markers of Anabolism and Catabolism. J Int Soc Sports Nutr. 2004 Dec 31;1(2):12-20.

The Neurotransmitter Depleting Effects of Branched Chain Amino Acids (BCAAs) and Their Potential Ergolytic, Anxiogenic & Depressive Downstream Effects

Oh yes, this will happen despite if not because you've taken large amounts of BCAA before the workout.

Usually you don't put the cart before the horse, but I guess you won't mind if I do so and postpone a summary of the information on magnesium from yesterday's installment of the Science Round-Up to tomorrow, when this means that we are going to take care of the "BCAA crisis" today.

Ok, maybe "crisis" is not the best word to describe the reverberations the recent publication of a study by SuJean Choi et al. should be having (=nobody buys BCAAs anymore), but I was looking for something better than the usual "the truth about..." Science, and I am not going to tire repeating that, is after all not about truth (that's what the confessional box is about), but about experimentally verifiable/verified and non-verifiable/non-verified hypothesis (Popper. 1994).

BCAAs can have ergolytic effects - A verifiable hypotheses?

Based on the observations Choi et al. made in by then decapitated lab animals (so much about the "why don't they prove this works in humans"-argument), the administration of a solution that contained either a BCAA + Arginine + Glutamine mix, or one out of two different EAA mixtures, it is safe to say that the hypothesis formulated in the subheading of this paragraph could belong to the former, i.e. the verifiable, hypothesis; and that despite the fact that the addition of glutamine and arginine to the human equivalent of 19:12:12 mg/kg body weight of leucine:isoleucine:valine (less than most BCAA products offer) would at least buffer the previously discussed performance decrements due to the accumulation of ammonia (learn more)

Table 1: Amino acid composition (mg/kg body weight) of the AA supplements tested (Choi. 2013)

In the end, the results Choi et al. present contradict both, the promises on the labels of the countless BCAA products and Newsholme's and Blomstrand's hypothesis that the inhibitory effect the BCAAs exert on the uptake of tryptophan from the blood into the brain and the way this forestalls the subsequent conversion of tryptophan to serotonin would lead to a reduction of central fatigue during exercise (Newsholme. 1996).

Figure 1: Effects of BCAA and BCAA + 100mg/kg l-tyrosine supplementation on serum and brain amino acid and neurotransmitter levels in sedentary rats; data expressed relative to vehicle (Choi. 2013)

Now, the data in figure 1 does confirm the first part of the Newsholme + Blomstrand hypothesis: The adminstration of BCAAs in an amount similar to many low dose BCAA supplements that are currently being marketed as ergogenic agents does blunt the increase in serotonin by competitively inhibiting the uptake of l-tryptophan from the bloodstream. The latter is a necessary consequence of the fact that both the BCAAs and the said 5-HTP (=serotonin) precursor are being transported by the same large amino acid transporter (think of it like a taxi that is allowed to pass the blood brain barrier) as l-tryptophan.

A note on the pro-obesity effects mentioned during the show: While some scientists invoke the increased BCAA levels in obese individuals and the subsequent blockade of serotonin (and dopamine) production in the brain to the constant insatiable cravings, anxiety and depression in these individuals (Breum. 2003; She. 2007; Coppola. 2013) a more fundemental contribution to the obesity pandemic has been proposed by Newgard et al. (2009). Their hypothesis is that a continuous presence of BCAAs in the blood will lead to a continuous overexpression of mTOR that increases the susceptibility to diet induced obesity and insulin resistance.

Now, it is also true that this will blunt the increase in 5-HTP synthesis in the brain (-48%; in the absence of exercise; see figure 1), but with the concomitant -25% decline in hypothalamic DOPA (=dopamine, the "get going neurotransmitter") in the brain after ~30min, the net ergogenic effect will, just as it was the case in the majority of pertinent rodent and human studies, be negligible, at best!

Modulatory Effects of Different Macronutrient & Stress Compositions on Serotonin (read more)

"Following oral intubation with the ‘‘BCAA’’ mixture to sedentary rats (see Table1; n=3/group), serum TRP and TYR concentrations showed non-significant reductions; the serum TRP and TYR ratios, and cortical TRP and TYR concentrations dropped markedly at 30 min. Cortical TRP and TYR concentrations remained low for the duration of the study (120 min), while the ratios began to recover at 90–120 min. DOPA and 5HTP synthesis dropped to nadir values at 60 min; DOPA synthesis remained low, while 5HTP synthesis had rebounded by 120 min (bottom panels, Fig.2).

Inasmuch as the maximal effects on DOPA and 5HTP synthesis occurred 60 min following intubation, all subsequent studies used 60 min as the experimental endpoint." (Choi. 2013)

In fact, the overall and as you've just read persistent drop in neurotransmitter levels can not only make you tired, previous research even suggests that it may be invoked in the etiology of depression / central fatigue (see previous SuppVersity post "Study Investigates Modulatory Effects of Different Macronutrient Compositions on Serotonin in the Presence and Absence of Stress" | read more).

Balancing leucine with tyrosine at a ~1:1 ratio helps

The data in figure 1 does however also tell you that you can mitigate the problem by the addition of 100mg/kg body weight of l-tyrosine to the supplement. With that being roughly equivalent to the amount of leucine in the BCAA formula (cf. table 1), this is yet far more of the dopamine precursor than your average BCAA product is going to have... after all it's a maximal leucine concentration that sells and is propagated as being "modern" and "maximal anabolic".

Figure 2: Hypthalamic DOPA and 5HTP levels after BCAA or BCAA + 100mg/kg tyrosine ingestion with / without exercise, left (Choi. 2013); effects of BCAA or l-tyrosine supplementation on time to exhaustion (Strüder. 1998)

With the addition of 100mg/kg l-tyrosine, you may yet in fact expect to see some benefits. Unfortunately, the currently available literature will put you right in a study that was conducted by Strüder et al. for example neither 21g of BCAAs nor the whopping dose of 20g of pure l-tyrosine resulted in the expected increase in the time-to-exhaustion during time trials in trained cyclists (see figure 2, right; Strüder. 1998) and Blomstrand concludes in his review for the British Journal of Sports Medicine's A-Z Supplement Review Series:

"Under certain conditions, BCAA supplementation can also improve physical performance, although the majority of studies have found no effect of BCAA on performance when supplied together with carbohydrates." (Blomstrand in Burke. 2009)

This, on the other hand, tells you that the performance enhancing effects are a mere result of the oxidation of BCAAs of which both Blomstrand, who is by the way defending his own hypothesis here, and the recently discussed by Falavigna et al. (see SuppVersity News) indicate that the ensuing increased release in ammonia production "may be detrimental to performance" (Blomstrand in Burke. 2009). If you also take into consideration that a study by van Hall et al. from 1995, i.e. before Newsholme & Blomstrand came up with the hypothesis the whole BCAA myth was built on, basically falsified the tryptophan hypothesis of fatigue, In the pertinent study the scientists were after all able to show that the provision of BCAAs as workout fuel is not superior to that of tryptophan and that despite a 8-12% reduction in brain tryptophan uptake at exhaustion with BCAAs and a 7- to 20-fold increase in response to the ingestion of a tryptophan supplement (van Hall. 1995).

Milk protein EAAs: An option, but a logical one?

If you finally take a look at the data in figure 3  you will notice that the head-to-head comparison would place an amino acid pattern as the one you can find in milk proteins, would probably be the best amino acid supplement source to resort to (don't ask me what exactly it is that makes the difference, I can't tell, but suspect it could be related to lysine which is also going to block the same small AA channel into the brain + the inclusion of non-essential amino acids in milk protein vs. pure EAAs).

Figure 3: Comparison of the the effects of BCAA, regular EAAs and an EAA amino acid mix from milk protein; composition of the mixtures see table 1 (Choi. 2013)

But let's be honest, does it really make sense to buy an additional supplement, when you already have a pouch of cheap and tasty whey and/or another fast digesting high BCAA protein such as pea protein lying around at home?

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So what's the verdict then? As you've heard on the Science Round-Up, yesterday, I personally think that this does not make sense, because ...

1. .

   

   Suggested Read: "Spiking Whey W/ EAA Will Provide Inferior Results" (read more)

   .. neither the total amount of amino acids that are obsorbed within 1h from free form EAAs, nor the the utilization speak in favor of EEAs - both have been shown to be +7% and +92% higher with slightly hydrolized whey vs. EAAs (Monchi. 1993),
2. ... nor is there any anabolic benefit to the addition of EAAs or leucine to whey, in fact "25 g of whey is better suited to increase resistance exercise-induced muscle anabolism" compared to lower amount of whey that has been pimped with additional EAAs and leucine to offer the same amount of the purpoted "anabolics" as the 25g dose of plain whey protein (click on the picture to the right to learn more; Churchward-Venne. 2012)

Contrary to Carl's jovial suggestion to simply throw away your BCAA supplements, I would suggest you keep them (unless you already have problems with anxiety, etc.), cut back on the dosage and monitor your response closely. The latter is especially true, when you take them on an empty stomach. After you've run out, train a month with nothing but cheap protein and decide afterwards whether or not your past "great training experience", "superior intensity" and whatever else the ads tell you the respective products will do was more than just another instance of the brocebo effect (learn more about brocebos).

References:

• Breum L, Rasmussen MH, Hilsted J, Fernstrom JD. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am J Clin Nutr. 2003 May;77(5):1112-8. 
• Burke LM, Castell LM, Stear SJ, Rogers PJ, Blomstrand E, Gurr S, Mitchell N, Stephens FB, Greenhaff PL. BJSM reviews: A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 4. Br J Sports Med. 2009 Dec;43(14):1088-90.
• Choi S, Disilvio B, Fernstrom MH, Fernstrom JD. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines. Amino Acids. 2013 Aug 1. [Epub ahead of print] 
• Coppola A, Wenner BR, Ilkayeva O, Stevens RD, Maggioni M, Slotkin TA, Levin ED, Newgard CB. Branched-chain amino acids alter neurobehavioral function in rats. Am J Physiol Endocrinol Metab. 2013 Feb 15;304(4):E405-13.
  
• Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SM. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2012 Jun 1;590(Pt 11):2751-65.
• Monchi M, Rérat AA. Comparison of net protein utilization of milk protein mild enzymatic hydrolysates and free amino acid mixtures with a close pattern in the rat. JPEN J Parenter Enteral Nutr. 1993 Jul-Aug;17(4):355-63. 
• Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS Jr, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009 Apr;9(4):311-26.
• Newsholme EA, Blomstrand E. The plasma level of some amino acids and physical and mental fatigue. Experientia. 1996 May 15;52(5):413-5. Review.
• Popper, KR. Zwei Bedeutungen von Falsifizierbarkeit [Two meanings of falsifiability]. In Seiffert, H.; Radnitzky, G. Handlexikon der Wissenschaftstheorie. München: Deutscher Taschenbuch Verlag. 1994.  
• She P, Van Horn C, Reid T, Hutson SM, Cooney RN, Lynch CJ. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1552-63. Epub 2007 Oct 9.
• Strüder HK, Hollmann W, Platen P, Donike M, Gotzmann A, Weber K. Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans. Horm Metab Res. 1998 Apr;30(4):188-94.  
• van Hall G, Raaymakers JS, Saris WH, Wagenmakers AJ. Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect performance. J Physiol. 1995 Aug 1;486 ( Pt 3):789-94.