Eating 75-100g Fat (M-/PUFA) in the AM Improves Glucose (7-8%), Insulin (40-60%), Trigs (4-16%), GSH & MDA (40-75%)

If we assume that the protein fried eggs with its comparatively low insulinogenicity is not a problem (unlike your whey, for example), avocado and eggs fried in olive oil is the perfect breakfast to replace the liquid test meal used in the study.

There's no debating that increased amounts of free fatty acids in the blood will impair your insulin sensitivity, as they should be there only, when your supply of carbohydrate is running out, AMPK and with it the expression of lypolytic enzymes increase and the triglycerides from your fat stores are broken down into free fatty acids and released into your bloodstream where they can be used by liver, muscle and other organs as an alternative energy source.

Now, the word "alternative" is of paramount importance, here, because you'll find yourself being in (diabetic) trouble if those FFAs pile up on top of high glucose levels. This is what happens with the SAD diet and its high carbohydrate and fat content (and energy!) content.

You can learn more about fat at the SuppVersity

Are Men Fat- & Women Sugar-Cravers?

Fat, not Fructose Cons. Increased in the US

Adding Fats to Carbs Does not Reduce Insulin

The Forgotten Pro-Insulinogenic Effects of SFAs

Margarine Not Butter Incr. EU Waists

Low Fat to Blame for Low Vitamin D Epidemic?

It's a vicious circle: When the levels FFAs are up, insulin sensitivity goes down (after all, with a normal diet you'd have to burn the fat and spare the precious glucose | Bodne. 1997; Koves. 2008). Since there's more and more glucose spilling in over the portal-vein, though, insulin will keep increasing to a point where it does no longer simply impair, but almost block the oxidation of free fatty acids. Now, without insulin working its glucose shuttling magic, however, the cells begin to starve for glucose and... right, more FFAs are being released, the insulin resistance increases, still hardly more glucose is being shuttled into the cells to restore AMP to ATP and the process continues.

What does all of that have to do with eating more MUFAs and PUFAs to control your glycemia? Well, nothing and everything. First- and most importantly, it should remind you that this is not about eating fat with your carbohydrates. That's exactly not what the latest study from the Hospital Clínico Universitario Valencia in Spain would suggest, even though I bet you will have some idiot already have misinterpret the study in this way "for your" online. Rather than that the study was, as the abstract already tells you, conducted to ...

"[...] evaluate the changes in glycemia, insulinemia, and oxidative stress markers during an oral fat load test in nondiabetic subjects with abdominal obesity and to analyze the association between postprandial oxidative stress markers and postprandial glucose and insulin responses" (Martinez-Hervaz. 2016)

This quote also contains another important information you will have people with an agenda forget to mention: the subjects in whom the fats worked their magic were abdominally obese! Later on we will see why this is relevant and why the same rules won't apply to lean individuals, but for the time being let's firstly take a look at the exact characteristics of the N = 40 (total) subjects in the study in Table 1.

Table 1. General characteristics, fasting lipids and lipoproteins, glucose, insulin and HOMA index values in the studied groups (Martinez-Hervas. 2016); ^a control vs abdominal obesity group (p<0.01).

Even though the discriminating feature, i.e. the characteristic the scientists used to find subjects for the two groups was their waist circumference (>102/88 cm for men and women, respectively vs. <102/88 in the control group), it shouldn't surprise you that the scientists have also observed sign. differences in other anthropometric and metabolic markers such as the BMI, the level of triglycerides, blood lipids and postprandial glucose levels after an oral glucose tolerance test (OGTT | see Table 1).

Is it a problem that the male / female ratio differed? That is difficult to tell. We do know that men and women handle nutrients, esp. fat and carbs slightly differently, but I doubt that the difference between an 11/9 ratio in the control group and a 7/13 ratio in the abdominal obesity group will ruin the results of the study at hand. Nevertheless, this should be addressed in future studies.

After initial testing, the subjects from both groups ingested the same commercial liquid preparation of high-fat meal of long chain triglycerides. The product is called SuperCal and must not be confused with a vitamin D + calcium product with the same name that is being sold on the US market. From a previous European study, I've got some extra-information about its composition, namely that

"[...] 125 ml contains 60 g fat, of which 12 g are saturated, 35.35 g are monounsaturated, and 12.75 g are polyunsaturated. Each 100 ml contains <1 g lauric acid, <1 g myristic acid, 4.8 g palmitic acid, 1.4 g stearic acid, 27.7 g oleic acid, 9.6 g linoleic acid, 1.4 g behenic acid, and 0.5 g lignoceric acid" (Fernández‐Real). 

The detailed fatty acid composition of the SFAs, MUFAs and PUFAs emulsion that was administered at a dosage of 50 g fat per m² of body surface (calculate your body surface if you want to know your individual equivalent dose = result of your calculation in m² x 50g g/m²; e.g. 1.78 m² x 50 g/m² = 89 g of fat) at 8:30 after an overnight fast is not mentioned in the Martinez-Hervas study. What the authors of the study at hand tell us, however is that the likewise relevant ratio ω6/ω3 is > 20/1 - similar to the average diet, by the way; a fact that excludes that this is an omega-3 effect we are seeing, here. Similarly, exercise or previous meals, shouldn't have messed with the results, either. After all, in both groups, only water was permitted during the "eating" or rather "drinking" process, and no physical exercise was undertaken before or during the "fasted" fat loading test in the AM.

Figure 1: Overview of the rel. levels of glucose, insulin, HOMA-index, trigs, the GSSG/GSH ratio and MDA, a byproducs of lipid oxidation (Martinez-Heras. 2016); levels expressed relative to control at baseline (T = 0), see explanation below

In order to make the data more accessible (compared to the tabular overview of absolute values in thee FT) for you, I've standardized each of the measurable variables to match 100%. This means that all the fasting bars at T = 0h will be at the 100% mark, because they are what the effects of fat loading are compared to. Let's take a look at two examples:

• 

  PUFA Increases Postprandial Thermo-genesis in Women & Beyond - 14% Increase Over MUFA & SFA Sounds Huge, But Does it Matter?

  Insulin: In contrast to what you will see if you co-administer fat and carbohydrates (learn more), the administration of the high MUFA + PUFA fat supplement in the absence of carbohydrates lead to a sign. reduction of the initially 3.8-fold increased insulin levels. Not to normal levels, but at least to 158% (i.e. 1.6-fold elevated) of the fasted value of the lean subjects. Ah, but remember: All that happened with the fat load, alone, and in the absence of CHOs. In the presence of carbs the results would have been much different.
• GSSG/GSH ratio: The effects on the ratio of 'used' glutathione (GSSG) to the amount of the 'fresh' master anti-oxidant (GSH) were quasi the opposite of what the scientists observed for insulin. Here, the abdominally obese group had 2.4x elevated levels to begin with. This tells you that, compared to the normal controls, their anti-oxidant status was a mess. After only 8h, however, their GSSG/GSH ratio had not just declined, it was actually lower than the fasted value of the control group.
  
  And again, likewise similar to the effects on insulin, the control group saw benefits as well, with a 64% decrease in the GSSG/GSH ratio their antioxidant defenses did also benefit from the MUFA + PUFA load in the AM.

For other parameters you will see similar, for many of you probably surprising benefits. Things to keep in mind, though, is that we are talking non diabetic subjects in both groups, even if the abdominally obese subjects had fasting HOMA index values fourth fold higher than controls, higher fasting triglyceridemia and higher fasting oxidative stress markers. If that sounds like you, then the acute ingestion of ~75-120g (depending on your body surface) of fat on empty in the AM, when hyperlipidemia is not that much of an issue, you can benefit from a high MUFA + PUFA fat load as you would find it in an avocado + egg fried in olive oil, for example... or, as the authors of the study at hand have it:

"[O]ur study has demonstrated a significant reduction of postprandial glycemia, insulinemia, c-peptide and oxidative stress markers using an acute oral overload of unsaturated fat. We have found a significant correlation between oxidative stress markers and postprandial lipemia. There is an increase of TG achieving the maximum peak four hours after the beginning of the test. However, although postprandial lipemia has been implicated in the development of insulin resistance and oxidative stress, and despite the increase of TG, there are significant reductions of the HOMA index and oxidative stress markers" (Martinez-Hervas).

Even though you may think otherwise, the authors are also right, when they point out that "[t]he influence of dietary macronutrients in insulin sensitivity is not well known" (ibid.) This is especially true, when we begin mixing proteins, carbohydrates and fats and start to take into consideration that we can have a dozen of types of the three in a single meal.

What about me? I am not abdominally obese, will I benefit, too? If we assume that you deprive yourself of any carbohydrates (and proteins?), you should see the same benefits as the subjects in the control group - those are lower than what we see in the big belly group and may simply be a result of the moderate energy intake (that's < 900kcal before an 8h fast even for many bigger guys), it would appear as if the answer to your rightly asked question would be "Yes, you can benefit, as well." Whether this will also require you to abstain from all, not just insulinogenic dairy proteins, however, will have to be tested in future studies.

It may thus depend on the food-matrix whether the results of previous studies, most of which clearly indicate that saturated fat will increase in fasting and postprandial insulin resistance would have yielded different results if the meals were administered in the absence of carbohydrates, for example - even though, additional evidence traced these effects back to increased levels of saturated fat in the cells' phospholipids that can alter their phyco-chemical properties and decrease the glucose transporters (while MUFA and PUFA have been shown to do the opposite | Borkman. 1993). Martinez et al. who have not actually tested the effect of SFAs in their studies provide additional evidence in their discussion:

Will the additional butter on top of the potatoes reduce the insulin response? You can find the answer to this and the other questions in today's episode of "True or False?" | Learn the answer

"Iggman et al demonstrated in elderly men that palmitic acid, the major saturated fatty acid found in adipose tissue, inversely correlates to insulin sensitivity measured by euglucemic-hyperinsulinemic clamp. However, they also found a positive relation of insulin sensitivity with the content of linoleic acid in adipose tissue (Iggman. 2010). It is in accordance with our results because our commercial liquid preparation of high-fat meal of long chain triglycerides is composed in the majority by linoleic acid (59%). Furthermore, in line with our findings, the replacements of dietary saturated fat by unsaturated fat also improved fasting insulin sensitivity (Vessby. 2001).

Several other studies have demonstrated that unsaturated fat improves fasting and postprandial IR, although the mechanism is largely unknown (Wang. 2015). Moreover the PREDIMED study has recently demonstrated that unsaturated fat can improve fasting insulin sensitivity and prevent the incidence of type 2 diabetes (Salas-Salvadó. 2011).

Another thing the study could not address is the chicken or egg question: After all, you can argue athat the significant reduction in oxidative stress markers the scientists throughout the fat load test could - as a result - have improved the subjects insulin sensitivity, but - at least in theory - it is imaginable that this worked the other way around... by an unknown feedback loop.

Figure 2: Relative in-group reduction in the parameters from Figure 1 from 0h to 8h (Martinez-Hervas); in contrast to the previous figure the one at hand shows the in-group difference, i.e. the change in control at 0 vs 8h, etc.

As you see, there's still lots to be learned about dietary fat out there - including the fact that a "high fat" diet that combines high energy with high fat and high carbohydrate intakes is always detrimental for your health and should no longer be used in studies, unless the goal is to mimic the Western diet (and I beg scientists to then call it what it is, and that's not a "HFD").

Beware of dairy proteins, especially whey, but also casein are highly insolinogenic and may reduce if not reverse the effects of fat loading in the AM on glucose management and inflammation | learn more.

Bottom line: Before you get addicted to the previously suggested avocado + eggs fried in olive oil breakfast, please keep in mind that this is not what the scientists tested. Especially in view of the relatively high protein level in eggs, another study would have to make sure that the latter won't interfere with the benefits... even if that's much less likely for eggs, meat or fish than for the highly insulinogenic dairy proteins.

Furthermore, the study at hand cannot tell us anything about the long-term effects, because it is an acute intervention (not even lasting for 24h, there could have been a rebound at 12h or 24h or with the ingestion of another meal at noon, etc.) that suffers from another methodological problem.

Without a control supplement containing high(er) amounts of saturated fat, the assumption that the results were MUFA + PUFA specific is simply based on the scientists' review of the existing research (see previous elaborations + quotes). And as the scientists add, last- and [f]inally, oxidative stress markers analyzed could be also altered by others players regulating the postprandial state" (Martinez-Hervas. 2016) | Leave a comment, praise or criticism on Facebook!

References:

• Boden, Guenther. "Role of fatty acids in the pathogenesis of insulin resistance and NIDDM." Diabetes 46.1 (1997): 3-10.
• Borkman, Mark, et al. "The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids." New England Journal of Medicine 328.4 (1993): 238-244.
• Fernández‐Real, José M., et al. "Fat overload induces changes in circulating lactoferrin that are associated with postprandial lipemia and oxidative stress in severely obese subjects." Obesity 18.3 (2010): 482-488.
• Iggman, David, et al. "Adipose tissue fatty acids and insulin sensitivity in elderly men." Diabetologia 53.5 (2010): 850-857.
• Koves, Timothy R., et al. "Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance." Cell metabolism 7.1 (2008): 45-56.
• Martinez-Hervas, Sergio, et al. "Unsaturated Oral Fat Load Test Improves Glycemia, Insulinemia and Oxidative Stress Status in Nondiabetic Subjects with Abdominal Obesity." PloS one 11.8 (2016): e0161400.
• Vessby, Bengt, et al. "Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study." Diabetologia 44.3 (2001): 312-319.

Six Cups Of Coffee (900mg/day): Three Too Much or Just About Right to Speed Up Lipolysis & Fatty Acid Oxidation?

The human equivalent of almost 900mg caffeine per day used in the study at hand did some good, but it also did some harm - read more and decide for yourselves which one you'd consider more important.

It amazes me time and again. Coffee and caffeine in particular are unquestionably the best-researched "supplements", nutraceuticals, drugs, or whatever you want to call. Yet, nevertheless, the number of interesting studies is increasing day by day. Let's see... 2.3+ studies related to caffeine in one way or another were published per day in 2012 and as of now it looks, as if we would easily top that this year. But enough of those stats. Let's get to one of the latest of the 515 hits for this year and take a look at what Eun-Young Choi and Yun-Ok Cho from the Department of Food and Nutrition at the  Duksung Women's University in Seoul has to bring to the table.

What? Another rodent study?

Yeah, I hear you. I would also prefer if the Korean scientists had taken human subjects fed them a standardized diet and gave them water with 0.12 g freeze-dried instant coffee/100 g body weight for 4 weeks, but I hardly doubt the Ethics Committee would have approved of the guys and girls being sacrificed and their organs being harvested at the end of the 4-week period to check, whether or not the combination of coffee supplementation, which was combined with a chronic exercise (treadmills for 30 minutes; 5 d per week, 15° incline, 0.5-0.8 km/h; the dosage was chosen to approximate maximal quantity reportedly consumed by physically active individuals, i.e. 895 mg of caffeine/60 kg/d) regimen in 50% of the animals exerted independent (c) or combined effects on the organ weight liver as well as the liver and muscle glycogen content or not (data see figure 1).

 Figure 1: Effect of acute exercise, training (=chronic exercise) and chronic caffeine intake on heart, spleen, liver and visceral fat weight  (left), serum glucose and liver and muscle glycogen (Choi. 2013)

Luckily, it is quite unlikely that the overall effect of training + supplementation, of which you can see in figure 1 that only the former or a combination of both did have significant effects on heart weight, visceral fat and liver glycogen content, would have been fundamentally different, if the study had been conducted on human beings.

"The heart weights were significantly higher in the two training groups (TC, TCF) than the two control groups (NTC, NTCF). The combined visceral fat masses were significantly lower in the two training groups (TC, TCF) than the two non-training groups (NTC, NTCF). No significant effects on spleen and liver weights were being observed." (Choi. 2013)

As far as the caffeine or rather "simulated coffee consumption" is concerned, however, only the change in liver glycogen was affected. Particularly,

• the chronically trained, caffeine guzzling rodents exhibited the higher liver glycogen levels (measured before acute exercise), while 
• the animals in the non-trained caffeine guzzling group who had been sacrificed immediately after a final short bout of exercise at the end of the fourth week had the lowest liver glycogen concentration 

Overall, "coffee intake decreased liver glycogen levels in the T group, but no significant differences were observed" (Choi. 2013) in the non-trained animals. The muscle glycogen levels, on the other hand, were not significantly effected by caffeine intake. The 4 weeks of training, on the other hand induced a statistically significant increase in muscle glycogen (after rest) in the trained vs. untrained group of rodents - an observation that has previously been made in human studies, where chronic exercise in the presence of adequate carbohydrate nutrition will progressively increase the size of the muscular glycogen stores (supercompensation principle).

Similar to the increase in muscle glycogen during the 4-week training regimen, the observation that all training and/or supplementation regimen increased the amount of free fatty acids (FFA). What may come as a non-necessarily positive surprise to everyone with elevated baseline FFA levels, though is that addition of caffeine to the equation effectively doubled the training induced increase in resting FFA levels in the caffeine + training group. The beneficial effect of training on liver and muscle triglyceride levels, on the other hand, was not significantly impaired. And what many of you will probably deem about as important: caffeine did not affect the muscle, liver and plasma protein levels.

So what did the study find then?

If we summarize the above, the main findings of the study at hand were not exactly revolutionary, but there were some. Worth mentioning are ...

1. 

   Suggested read: "Coffee - The Good, The Bad & The Interesting: 2-4 Cups of Coffee for Adiponectin. Roasted Filtered Coffee & High LDL!? The Optimal Caffeine / Taurine Ratios & the Buzz ". Learn more about the good and bad sides of coffee / caffeine and find out whether taking taurine may buffer the side effects w/out compromising the benefits of exuberant amounts of caffeine, as they have been used in the study at hand? Or will it make things even worse? It certainly won't hurt the liver that's for sure (read more).

   an increase in free fatty acid release and usage during workouts (already well-established), which resulted in slightly more significant reductions in visceral fat, when training and caffeine were combined, 
2. a highly desirable and significant reduction in liver fat in the trained rodents "on coffee" (all day), and a greater reduction in liver trigs in the animals that were only exercised once
3. a more pronounced "in-and-out" of muscle triglycerides in the trained coffee guzzlers with significantly higher levels of muscle triglycerides before and significantly lower muscle triglyceride levels after a workout (probably a mechanism which contributes to the endurance boosting effects of caffeine; Sherman. 1995)
4. a (surprising?) null-result for changes in plasma glucose that should put the "caffeine will give everyone diabetes" fears at rest; you should however remember that the FFA increase can generally become problematic overtime, if there is a concommittant influx of fatty acids from the diet and no fasting / exercise to keep the overall levels in check
5. a significant reduction in glyocogen storage in the liver after a workout, of which I am yet not sure if this was not a result of a reduction in hepatic glycogen depletion due to the increase in fatty acid oxidation (the scientists do state that the training + caffeine group had the highest glycogen levels in the rested state)
6. no effects on muscle glycogen or protein, and no effect on protein levels in other tissues due to caffeine
7. a significant reduction in hematocrit in the coffee group the scientists ascribe to the hampered absorption of dietary iron

The overall image that emerges is thus rather a negative one - allegedly the increased visceral fat loss in nice, but it is not statistically significant compared to training alone (low iron = low oxygen carrying capacity = low performance; plus: low iron also hampers fatty acid oxidation so that even this benefit may be lost over time.

Another thing Alex Leaf, without even knowing it, reminded me about are the night-sweats and the 4AM wake up call, I know only too well from my own experience with copious amounts of stimulants. They could in fact be brought about by the inability to regenerate liver glycogen fast enough and the subsequent failure of providing your body with glucose from the liver while you sleep. This in turn will have you go hypoglycemic overnight. Your body reacts by spilling out stress hormones that will heat and wake you up...

---

Those three cups are probably as good as it gets, they protect your heart and can ward off cancer (learn more).

Bottom line: In view of the observed downsides, of which I would argue that (5) may actually be the worst for a healthy athlete, the study at hand appears to underline what I have told you before: the consumption of the equivalent of 800-900mg of caffeine per day is clearly counter-indicated even if you don't consume it all at once, and alongside its natural co-factors in coffee (learn more about coffee).

Stick to max. 400mg per day and you are more likely to get the benefits without the sides, about which you have read only a couple of days ago in a SuppVersity article discussing the acute ergogenic effects and accompanying side effects of different doses of caffeine (read more).

References:

• Sherman WM, Leenders N. Fat loading: the next magic bullet? Int J Sport Nutr. 1995 Jun;5 Suppl:S1-12. Review.

19x Increase in Growth Hormone 60min After Ingestion of 1g of Glycerophosphocholine (GPC) in Young Male Subjects

Image 1: Don't worry one thing is sure - GPC won't give you a gut like that ;-)

A couple of days ago, I have written about the exorbitant choline consumption of some of bodybuilding legends, Randy Roach writes about in his Muscle Smoke & Mirrors Vol. II  and to be honest, I was quite surprised that among the many responses I got, none broached the issue of the latest and greatest supplemental choline spin-off: Glycerophosphocholine, or short GPC - a supposedly superior, because fat-bound (hence "glycero" as in "glycerol) and highly bioavailable bean-derived form of choline. Whatever the reasons may be, I suppose you still won't mind to hear that a recent experiment that was conducted at the Faculty of Sport and Health Science of Ritsumeikan University in Shiga, Japan, yielded quite interesting results with respect to the endocrine and metabolic short-term effects of 1,000mg of GPC in 8 healthy male (25+/1y) subjects (Kawamura. 2012).

19x more growth hormone 60 min after the ingestion of 1,000 mg GPC, ...

And no, the subheading above does not contain a typo, at least not in the number, which is "nineteen" as in +1800%, which was, as the data in figure 1 shows, the average increase in serum growth hormone concentration exactly 60 minutes the lean subjects (11% body fat) experienced after ingestion of the GPC caps compared to placebo (the study was double-blinded and randomized, there was a period of two weeks in-between the testing days).

Figure 1: Fatty acid metabolism (left), choline levels (middle) and growth hormone levels (right)  6min0 and 120 min after the ingestion of placebo pills or 1,000mg glycerophosphocholine (Kawamura. 2012)

It is unquestionable the data in figure 1  looks pretty impressive. Yet not all changes are in fact statistical significant (I marked them by adding the relative differences between active and placebo arm) and as exciting a growth hormone spike of +1800% may sound, the subsequent drop to levels below the placebo arm should remind you, a seasoned SuppVersity veteran of the futility of supplemental "growth hormone secretagogues", such as arginine, leucine, a combination of both etc.; they all share a fundamental weakness - after each spike there is a huge trough.

...but just  6.88x more GH production over 2h

And therefore it should not really surprise you that we have the 2-h AUC, i.e. the area under growth hormone curve, a measure for the total amount of growth hormone that is released in the course of the timespan for which the AUC was measured, was "only" 6.88x larger after the ingestion of the glycerophasphatecholine supplement, than after placebo(cf. figure 2).

Figure 2: 2h AUC for free choline, free fatty acid, 3-hydroxbutyrate (ketones) and growth hormone after the ingestion of 1,000mg GPC; data expressed relative to placebo control (Kawamura. 2012)

Still, even this obviously transient increase in growth hormone in the fasted that occured in response to the +38-51% increase in circulating plasma choline went hand in hand with profound increases in free fatty acids (due to the lipolytic effects of GH; cf. Marcus. 1994) and ketone bodies, which is a sign of increased fatty acid metabolism must be a good thing,... right? It would appear so, but without answering the following two fundamental questions "How does it work?" and "What does that mean", we will be having a hard time to justify this conclusion. After all, the ingestion of 4mg/kg caffeine have been shown to illicit a >500% increase in free fatty acids (FFA) after only 40min in trained subjects (LeBlanc. 1985) and still none of the caffeine laden "fat burners" with other ingredients, which further augment the lipolytic effects of caffeine will actively burn body fat.

So what's the mechanism of action? And what does it tell us about the real world implications?

The working principle Kawamura et al. suggest is actually quite straight forward: With increasing serum choline levels, the influx of choline into the brain will increase as well. This will augment the synthesis of acetylcholine, which, in turn, has been found to decrease the concentration of somatotropin release-inhibiting factors right at the hypothalamic level and thus disinhibit the production of growth hormone (Blusztajn. 1983). Put simply: Somewhere down the line the increase in serum choline will pull the breaks that keep your body from producing growth hormone.

A note to all the stim-junkies out there: I guess, you will be intrigued (or shocked?) to hear that blocking the catecholamine induced stimulation of the a2-adrenergic receptor with yohimbine has been shown to negate the aforementioned growth hormone promoting cascade. And that irrespective of whether you try to augment it by supplements or just want to keep your natural rhythm intact (Minamitani. 1989). The first real-world implication would thus be "don't take your GPC alongside alpha-2 antagonists such as yohimbine" (better not take those at all ;-)!

Now this raises the question does that matter? With arginine and lysine, we already know that it doesn't, but maybe we just have a larger effect size here? To answer the last question first - the spike is in fact spectacular and way above the average response to the long-touted GH boosters arginine, lysine or glutamine, which ranges from "no effect at all" (Carlson. 1989) over 4.5x (Welbourne. 1995) to the whopping 13x increase in response to an intravenous injection of  0.5 g arginine/kg (Tanaka. 1991). If do yet take another look figure 2 you will notice that I inserted a quote from Kawamura et al.'s discussion of the results into the graph - a quote that is of paramount importance to quantify the real world significance of these ostensibly HUGE increase in GH (which you will certainly see referenced by respective supplement manufacturers in their glossy marketing material, very soon):

"The GPC-induced increases in GH levels observed in this study were of a comparable degree to the increase induced by moderate-intensity exercise"

I guess, you don't need me to tell you how "effective" popping a couple of those pills is thus going to be compared to training and diet alone in furthering your muscle gains and fat loss. And in terms of overall and cardiovascular health, you should already know from my previous blogpost, "Old School Supplements: Choline  Faster, Stronger, Leaner & more Muscular" that regular dietary choline as in eggs, meats, fish, leafy greens, etc. will do just as fine.

How much choline do you need? According to Coates et al. plasma choline concentrations can double after a 2-egg meal (~225mg choline) by up to two-fold (Coates. 2005). That would effectively be more than what we see as peak increase in the study at hand. And certainly puts the "need" for supplemental choline into perspective. The LD50, i.e. the purportedly fatal dosis, after the ingestion of which 50% of the subjects would die, is "of the order of 200-400g" (Gilman. 1980) - an amount of choline your tummy probably would not hold o to long enough to be absorbed, anyway ;-)

And in the unfortunate case that you do believe that you are running short of choline, because you don't eat all the good choline containing foods out of ethical or whatever other reasons, and thus insist on supplementing, I suggest you yourself a 500g container of choline bitartrate powder (don't let that become wet, though! It will stink like rotten fish ;-). Those 500g of choline bitartrate (40% choline, 60% tartate) will cost you about as much as 60x300mg caps of the overpriced GPC and has been "scientifically proven" (not in supplement company terms, but in SuppVersity terms) to safely increase circulating and brain choline levels and its metabolites after oral ingestion, as well (Stoll. 1996; Babb. 2004). And let's be honest, even if the effects on growth hormone were GPC specific - even on the boards, people have meanwhile realized none of those arginine + lysine GH boosters does make a difference and not because they would not produce transient increases in GH, but simply because those are physiologically meaningless and mostly compensated for in the course of 24h.

References:

1. Babb SM, Ke Y, Lange N, Kaufman MJ, Renshaw PF, Cohen BM. Oral choline increases choline metabolites in human brain. Psychiatry Res. 2004 Jan 15;130(1):1-9.
2. Blusztajn JK, Wurtman RJ. Choline and cholinergic neurons. Science 1983;221:614–20.
3. Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY. 2005. p. 108. . 
4. Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co. Inc. 1980. p. 1575. 
5. Carlson HE, Miglietta JT, Roginsky MS, Stegnik LD. Stimulation of pituitary hormone secretion by neurotransmitter amino acids in humans. Metabolism 1989;38:1179
6. Kawamura T, Okubo T, Sato K, Fujita S, Goto K, Hamaoka T, Iemitsu M. Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults. Nutrition. 2012 Jun 5. 
7. LeBlanc J, Jobin M, Côté J, Samson P, Labrie A. Enhanced metabolic response to caffeine in exercise-trained human subjects. J Appl Physiol. 1985 Sep;59(3):832-7.  
8. Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter SR, Garber AM, Hoffman AR. Systematic review: the effects of growth hormone on athletic performance. Ann Intern Med. 2008 May 20;148(10):747-58. Epub 2008 Mar 17.
9. Marcus C, Bolme P, Micha-Johansson G, Margery V, Brönnegård M. Growth hormone increases the lipolytic sensitivity for catecholamines in adipocytes from healthy adults. Life Sci.1994;54(18):1335-41.
10. Minamitani N, Chihara K, Kaji H, Kodama H, Kita T, Fujita T. Alpha 2-adrenergic control of growth hormone (GH) secretion in conscious male rabbits: involvement of endogenous GH-releasing factor and somatostatin. Endocrinology 1989;125:2839–45.
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Fat & Fit! Cardio Training Triggers Genetic Switches Which Won't Make you Lean, But Maybe Healthier.

Image 1: Does this remind you of
someone at your local gym? (Image
from Stanford School of Medicine)

As a trained physicist I am more interested in the "why's" than in the "what's". It is old hat that the combination of diet (usually incorporating a moderate caloric reduction) and exercise still is the most promising way to sustainable weight loss and metabolic health. The molecular and genetic underpinnings of their almost magical synergy, however, have still not been 100% elucidated. A recent study (Fu. 2011) from the Tianjin Medical University in Tianjin, China, does now contribute another piece to the complex puzzle that is our metabolism.

Published in the latest issue of the clinical and experimental branch of Metabolism Li Fu and his colleagues report the results of an experiment in the course of which 40 mice were assigned to one out of four intervention groups, two of which exercised on a mouse-treadmill for 60min/d five times per week in the course of the 6 week experiment:

• normal chow + treadmill exercise (NE)
• high fat diet + treadmill exercise (HE)
  
• normal chow + sedentary (NC)
  
• high fat diet + sedentary (HC)
  

The effect of the individual treatments at the transcriptional level, and selected genes were evaluated via oligonucleotide microarray measurements and confirmed by real-time polymerase chain reaction. As could be expected, the data showed "that 6 weeks of aerobic exercise improved the plasma lipid profile and reversed the glucose intolerance" in the high-fat fed mice.

Figure 1: Changes in body weight and blood parameters vs. sedentary control on normal diet
(calculated based on data from Fu. 2011)

Of greater importance, however, are the 503 genes of which the scientists found that they were "differentially expressed in samples of HCmice as compared with those of the NC group". By inter-group comparisons, Fu et al. were able to assign 40 of these genes to the effects of aerobic exercise.

Figure 2: Univariate variance analysis on body weight and plasma parameters (data adapted from Fu. 2011)

As the data (significance values) from a univariate variance analysis in figure 2 goes to show, the high fat diet (HFD) was associated with significant negative (red) effects on body weight, free fatty acids (FFA) and high density lipoprotein (HDL). Aerobic exercise, on the other hand, had beneficial effects on insulin total cholesterol and triglycerides, it did not, however, as so many frantic dieters expect, significantly reduce body weight. Neither did it prevent the HFD induced weight gain and that despite profound effects on the other negative effects of high fat feeding measured in this study.

These results stand in line with observations of Gary O'Donovan and colleagues (O'Donovan. 2011), published in the same journal. In a cohort of 183 nonsmoking white men aged 35 to 53 year O'Donovan and other researchers from the United Kingdom found profound differences in traditional and novel cardiometabolic risk factors (high-density lipoprotein cholesterol, triglycerides, alanine aminotransferase, and insulin resistance) between subjects who were fat and fit (like the exercised HFD mice) and those who were fat and unfit (like the unexercised HFD mice).

Image 2: Check out Johan's
amazing transformation to see
what mind-boggling results
you can achieve.

Taken together, these two studies confirm what many of you probably already knew: Aerobic exercise can ameliorate, yet not reverse, the damage you are inflicting upon your self by bad dietary habits (these are not the same for mice and men! A high fat diet - done properly - does not have to be detrimental to human health). Most importantly, aerobic exercise alone (and compensatory overeating) won't make you lose fat - in combination with appropriate lifestyle changes (note: I do not use the word "diet"!) and muscle building resistance training, it will do both: help you lean out and live a longer and healthier (an probably happier!) life.