Pre-Meal Protein Ingestion to Improve Glucose Tolerance: Insulin, GIP, GLP-1 - That's the Whey(!) it Works! Plus: Even Pure Glucose Can "Improve Your Insulin Tolerance"

Can a whey protein appetizer really undo the damage of greasy fast food? Probably not, but it's still interesting to see how it affects the postprandial glycemia.

Insulin resistance is the #1 contributing factor to the obesity epidemic and despite the fact the solution is already out there (read more about the necessary lifestyle modifications), it probably won't hurt to know if something as simple as having a high protein "appetizer" before a junky meal could improve blood glucose management even further, right? "Right, 'cause protein is always, good!" Ah, no... I guess the answer is a little more complex than that... Nevertheless, I still suspect that the results, Tina Akhavan and her colleagues from the University of Toronto present in their soon-to-be-published paper in the Journal of Nutritional Biochemistry will be of interest to you.

The study results are interesting, to say the least...

... and that's not despite but rather because the researchers did not use the usual subjects (rodents, obese individuals or elderly people), but young men (aged 18-29) with a BMI of 18.5-29.4 kg/m². In a randomized cross over design (cross over means that every subject got each treatment - obviously in seperate testing sessions), the subjects drank either...

• 300ml of a 10g or 20g whey protein solution, 
• 300ml of a 10g or 20g glucose solution, or
• 300ml of flavored zero calorie water 

The test drinks were consumed four hours after a standardized (junk = Honey Nut Cheerios + Skim Milk + Orange Juice) "breakfast". 30 min later the subjects were served even more junk in form of a *yummy* frozen Pizza from McCain Foods Ltd.

"Cereals", skim milk, pizza... whey alone won't help to counter that

The Pizza had been prepared "according to manufacturer‘s directions". This means that the reduction in glycemia the scientists observed in response to the protein preload were not because the pizza was still frozen... ok, before I produce even more nonsense, let's take a look at what the whey protein and glucose pre-loads did to the subjects blood glucose responses, right?

Figure 1: Glucose and insulin levels after pre-load and after meal (mean of 30-230min); all values expressed relative to water control, i.e. +85% would mean "85% higher than during control trial" (Akhavan. 2013)

If that's not your first visit to the SuppVersity, I probably won't have to explain the mechanism by which the pre-ingestion of whey (and glucose) reduces the Pizza-induced glycemia - do I? Well, I guess I better repeat it briefly:

1. The ingestion of the whey protein triggers a significant increase in insulin - 127% for the 10g and 191% for the 20g dosage.
2. Contrary to the glucose infusion there is no exogenous glucose that could lead to a rapid elevation of blood glucose (cf. figure 1, left → pre-values); the minimal increase you see is produced by gluconeogenesis in the liver.
3. With the elevated insulin levels, the mean glucose levels in the postprandial phase (30min-230min after the pizza ingestion) is lower with both the glucose and whey preload. The effect is however more pronounced with whey than with glucose. The reason should be obvious: The overall amount of glucose that's got to be stored away is lower.

I know it sounds counter-intuitive, but aside from (2) the mechanism is absolutely identical for the glucose trial - with the insulin already being around low (10g) glucose preload can actually lead to lower postprandial glucose levels than the water control (this is probably only true for healthy individuals).

Insulin? Is that all, or is there more to it?

Now that we have gotten the fundamental mechanism by the means of which "glucose-" and "whey-preloading" before eating pizza can ameliorate the blood glucose surge after the meal, let's take a look at the auxiliary data.

Figure 2: GLP, GIP, PYY, CCK and Ghrelin levels before eating the pizza; all values expressed relative to water control, i.e. +85% would mean "85% higher than during control trial" (Akhavan. 2013)

As the data in figure 2 tells you the increased insulin release was brought about and accompanied by profound increases in the production of the satiety hormones GLP-1 and CCK, as well as the "insulin trigger" GIP (all these changes occured in the pre-meal = pre-pizza phase, only). Ghrelin and PYY, which play an even more important role in the regulatory process that's supposed to control our energy intake, did not show significant treatment dependent differences, though.

What's the practical relevance of these findings? Honestly, I am not sure how relevant the findings from the study at hand actually are. I mean, from a "do this" or "don't do this" point of view - not from a "understanding how things work" perspective.

SuppVersity Suggested Read: "The Satiating Truth About Proteins and Why High Protein and Low Amounts of Low GI Carbs May Not Mix As Well As Most People Think" | read more

For those who would benefit most from reductions in postprandial glycemia, i.e. the obese type II diabetic, it is questionable whether (a) the mean 7% decrease is actually making a difference and whether it would (b) even occur in someone who is having a hard time producing enough insulin to have his / her body react to it.

For the lean individual, on the other hand, the 7% reduction in gylcemia probably doesn't matter at all and the insulin spike before the onslaught of a the "perfect storm" of carbs and fats from a greasy frozen pizza could (worst case scenario) increase the chance of fat storage - I mean the glucose can go to the muscle (learn more), the fat, on the other hand must end up in your adipose organ.

I would thus strongly advice everyone to stick to my "get 30g of quality protein with every meal" recommendation, instead of turning it into a "get 30g of protein before every meal". Aside from the questionable benefits of having the protein before your meal, having it with / as part of your mwal will also direct you away from pizza and towards healthier food choices. After all, you will be hard pressed to find a pizza with 30g+ of protein in it... and I bet the novel "pizza on a stick" I told you about on Facebook, recently, probably doesn't qualify either ;-)

References:

• Akhavan T et al. Mechanism Of Action Of Pre-Meal Consumption Of Whey Protein On
  Glycemic Control In Young Adults. The Journal of Nutritional Biochemistry. October 2013 [accepted manuscript]

Spot Reduce Abdominal Fat With Green Tea, Green Clay & Magnesium Sulfate Soaked "Plaster Body Wrap"... Really!?

No. Some green slime + cellophane is not going to make this possible within 5 weeks ;-)

I have been making fun of doing sit-ups to shed body fat in the midsection only recently on the SuppVersity Facebook Wall and what do I see today? A study that claims that a "plaster body wrap" could help you burn abdominal fat... what the f...at!?

First things first: In the "conflicts of interest" declaration at the end of the paper that is still in the "accepted manuscript" form, the authors declare no interest. If that's correct - and I simply assume it is - they probably have not yet patented their green tea + green clay + magnesium sulphate infused "plasters". This does not only mean that it is unlikely that the scientists "improved" the results of the treatment group; it does also mean that this could be your chance to make a fortune as a fat burning patch or fat burning oil, -creme or -whatever producer :-)

Why don't you test it yourself!?

Now, you all know that money doesn't grow on trees. So aside from a proper amount of entrepreneurship you will also need the will and patience to (1) massage your tummy with an alcoholic extract of green tea (alcohol at 96%) for five minutes (2) apply a solution of ~34g of green clay combined with ~19g of magnesium sulphate in ~17ml of distilled water to belly, (4) plaster your abs with plaster bandage that was previously impregnated with 3g of a green tea and another 7g of magnesium sulphate and finally (5) wrap yourself up in cellophane - go for it! If it works, it's your chance to make a fortune ;-)

In case you missed the recent SuppVersity Facebook post on "spot reduction": A Study from the 1980s says "5007 sit-ups won't shrink your belly by an inch" - I guess the 27-day sit-up challenge the scientists had their subjects perform will remind you of the "six-back" or "flat belly" specials in the Men's H. and Sh*pe magazines of this world; programs of which I can assure you that they will yield the exact same results as the one in the study: NONE → "Body weight, total body fat (underwater weighing), and fatfolds and girths remained unaltered." (Katch. 1984)

I guess the tone in the previous paragraphs has probably given away that I am still somewhat skeptical about the magical fat burning prowess of this "beer-belly remedy", but if you look at the results the 10 normal / pre-obese women in the active arm of this 5-week study you will have to concede: That's pretty impressive! Especially in view of the fact that ll they did to achieve that were two "fully wrapped" up endurance exercise sessions at 50% of their individual maximal heart rate reserve (=maximal heart - resting heart rate) per week.

Figure 1: Difference (active - control) in body fat / skinfold thickness (in cm) and calculated total body fat (caliper data) after 5 weeks with only two "fully wrapped" up 30min endurance sessions (Moreira. 2013)

Alright, I have to admit that the changes you see in figure 1 are pretty pathetic compared to the boastful promises the supplement industry uses to get rid of some Chinese herbal waste they label as "fat burner", "fat incarcinator", or "proven thermogenic". Nevertheless the mere idea that cellophane powered kitchen-sink approach to spot redution could actually work is impressive - don't you think so?

SuppVersity Suggested Read: "High Reps for "Spot Reduction" Works - Yet Not the Way Trainees Believe. Fat Loss Occurs in Untrained Body Parts" | read more

Make of the results whatever you want... and in case you feel inspired to try the "recipe", let me know how it worked. I promise I am not going to patent it before you can ;-)

Ok, enough of this nonsene. I guess, before you get totally psyched and wrapped up, it's worth mentioning that there is no specific information about the time-point when the ultrasound and skinfold measurements were taken. This may sound irrelevant, but if this was anywhere close to the last workout it is possible that the 10 subjects in the "patch" group simply lost more subcutaneous water than the 9 ladies in the control group and all those "significant results" were just measuring errors (in the broadest sense).

References:

• Katch et al. Effects of Sit up Exercise Training on Adipose Cell Size and Adiposity. Research Quarterly for Exercise and Sport. 1984; 55(3).
• Moreira JS, Carneiro Pinto de Melo AS, Noites A, Couto  MF,  Argel de Melo C, Freire
  de Almeida Adubeiro NC. Plaster Body Wrap: Effects in Abdominal Fat. Integrative Medicine Research. 2013 [accepted manuscript]

Maintain & Increase Your Insulin Sensitivity - Wrap-Up: Overview + 3 Stacks. Plus: AMPK & PPAR-γ Revisited

It's not about exercise or nutrition, it's about both of them. And as long as it is not about the former it should not be about supplements either.

It's Sunday and finally time for the wrap up of the "Maintain & Increase Your Insulin Sensitivity" Series (read all previous installments). It took me quite some time to get through all the compounds on my and your list and the outcome is far from being a "complete" list of all the agents that can have beneficial effects on your insulin sensitivity. Still, if there is at least one agent, one fact or one take home message for each of the 6 previous articles of which you would say: "Ok, I guess that was worth wasting some of my valuable time on", I would be happy.

For myself it was by the way yet another occasion to learn more  about many of the agents, I reviewed in this series.

And if you listened to the SuppVersity Science Round-Up on Thursday, you will probably remember that I said that I was at least a cautiously excited about the potential of berberine... but I am wasting your time here. Let's start with the wrap up.

Lifestyle changes are more powerful than supplements: So don't forget that it's imperative to realize the lifestyle changes described in the first installment of this series. Otherwise the best you can hope to achieve with supplements (and drugs) is to slow the progression from insulin resistance to full-blown diabetes.

Before we take a look at the three stacks I have compiled, I do just briefly want to get you up to speed as far as the major underlying mechanisms of the supplements are concerned:

• AMPK: Some people in the medical establishment think of it as the good counter-part to mTOR. The fairy that will put an end to the pro-carcinogenic reign of the evil mTOR-witch, so to say. Others, who are mostly part of the "muscle head" community, think of AMPK as their fiercest enemy and mTOR as their brother in crime... It goes without saying that neither of these views is accurate. AMPK and mTOR are not even necessarily antagonistic - at least not for people like you - people who work out regularly. The mTOR expression after a workout does after all occur in the presence of increased an expression of AMPK. What else could you possibly ask for, if you want to "recomp" (i.e. lose fat and gain muscle to improve your physical appearance)?
  
  

  

  Few people know that there are two different iso-forms of AMPK. The alpha-2 isoform is the one that's expressed during a workout and it works hand in hand with mTOR and not against it (learn more)

  What may at first look like a paradox is actually easily explained if we don't look at the characteristic downstream effects of mTOR and AMPK, but rather at the circumstances in which they are activated. Outside of the previously mentioned exercise context those are in fact antagonist. With mTOR being triggered by the abundance of nutrients - specifically protein, and even more specifically leucine - you would not expect to see increases of AMPK at the same time. The latter is after all, expressed, when a cell senses a lack of nutrients in form of an increase in ADP (~used ATP) and a decrease in ATP levels. The reaction, i.e. an increased expression of AMPK will then have downstream effects on the uptake of glucose and the oxidation of fatty acids, both of which contribute to a restoration of normal ATP levels in the cell.
  
  Both AMPK and mTOR act highly localized. The exercise induced glucose uptake is thus muscle-specific - that should be obvious, since exercise will raise the ADP levels only in the muscle. Supplemental agents that mimic this effect, on the other hand, act systemically. Agents like alpha lipoic acid will therefore increase glucose uptake in both muscle and adipose tissue (Moini. 2002). After a workout and at other time points, where the glucose uptake is already high and, more importantly, muscle specific, it is thus not necessarily the best idea to try to "escalate" the effects by using a class of supplements that is often mislabeled as "insulin mimetics". 
• A note on the PPAR-effects of CLA, fish oil, TTA & co: I guess as a well-read SuppVersity reader you will know that CLA is a supplemental non-starter. In human studies the outstanding results from rodent trials have never been successfully replicated. This could be - at least in parts - a result of the dosage and the ratio of t10c12 CLA to it's c9t11 counterpart, which has the exact opposite effects on the PPAR-gamma receptor (Toomey. 2005).
  

  

  Some of you will probably also remember my articles about the pertinent effects of TTA and fish oil in the. Of those only the latter has a significant PPAR-gamma activity. TTA, on the other hand is predominantly a PPAR-delta and -alpha agonist and thus more a "true fat burner" than a general "fat handler", which is probably the best way to describe fish oil (learn more).
  PPAR-gamma: If you listened to the Science Round-Up last Thursday you will have heard me say that blocking PPAR-gamma will inhibit the storage of energy in the adipose tissue. That's true, but by no means as beneficial as you may be thinking. It is, for example, pretty likely that the CLA induced PPAR-gamma blockade is also responsible for the increased propensity to develop non-alcoholic fatty liver disease in CLA fed rodents.
  
  The results Fedor et al. present in a 2012 paper, show that these effects can be ameliorated if the PPAR-gamma suppressor (i.e. trans-10, cis-12-conjugated linoleic acid) is combined with a supplement that exerts the opposite effects in the liver - a supplement you all know pretty well: DHA, as in "fish oil". It is, just like many of the "older" diabetes drugs, an (allegedly less) potent PPAR-G agonist (=activator; cf. Neschen. 2006).
  
  Whether the blockade of PPAR-gamma is a good or a bad thing does thus obviously depend on the scenario we are talking about. For the lean individual, who is working out regularly and wants to defend his leanness in the absence of (un-)wanted eating orgies and "mass building regimen" it is probably a good thing. He or she will not have an energetic surplus that could end up clogging up the liver. And while the same goes for the average obese individual who has finally gotten his act together, PPAR-gamma inhibitors would seem clearly counter-indicated for sedentary individuals on the high calorie, high sugar, high fat diet so many people consider "normal", these days.
  
  As paradox as it may seem, the anti-diabetic effects of PPAR-gamma activating thiazolidinediones (TZDs) which are still used to "treat" (I should rather write "manage") diabetes mellitus and other diseases that feature insulin resistance will thus come at the expense of increased body fat storage. The latter can be pretty pronounced,as the data from pre-diabetic individuals Bray et al. published only recently goes to show you (figure 1).
  
  Despite their anti-inflammatory effects and their (limited) use in highly inflamed type II diabetics you will therefore not find any of the herbal PPAR-gamma agonists like pomegranate, pumpkin, mellisa officinalis, morus alba, artemisia capillaris, bitter melon, guggul, banaba or mulberry (cf. Huang. 2009) in the stacks below. And that despite the fact that they have anti-inflammatory activities.

Ok, I guess you are either fed up of theoretical details by now, or were so before and just scrolled down to the "stacks" in the first place.

There is a reason there is no "athlete's stack" here: Since I know you will be asking, I thought I will say it right away. The reason that there is no "athlete's stack" in the list is that athletes are either "normal-weight insulin resistant" or they are insulin sensitive and don't need any supplements on top of the lifestyle changes from episode I. You got your workouts, folks: There is no better muscle specific insulin sensitizer out there! If you are looking for agents to stay lean try berberine, it's anti-ppar-gamma effects may help and if you want more, stack it with taurine, of which you should by now know that its benefits go well beyond "glucose sensitizing" / You don't? Well, then take a look at the previous articles about taurine.

I guess I will not make you wait any longer, then... I have come up with three scenarios, the "insulin resistant obese / overweight individual", "the normal-weight insulin resistant individual" and the "cheater" (explanations follow below the stacks):

• 

  Table 1: List of the most important supplements discussed in the series; more details on each of them, as well as on those I did not include in this overview can be found in the individual installments.

  The insulin resistant obese / overweight individual will have to target weight and fat loss and increases in insulin resistance; a stack that could facilitate all three would contain.
• Metformin - 3x 300-500mg (not lipoic acid, this is why)
• Berberine - 3x 200-400mg
• Fucoxanthin - 3x 5mg
• Taurine - 3x 2-3g
• Chromium - 1x 200mcg (*)
• The normal-weight insulin resistant individual will have to take care of inflammation, (usually) a beginning fatty liver and not taking the next step to the obese diabetic.
• Berberine - 3x 200-400mg 
• Chlorogenic acid - 3x 200-300mg
• Taurine - 3x 2-3g
• Milk thistle - 3x 200-400mg
• The cheater can be either of the former or a healthy perfectly insulin sensitive individual who wants to reduce the sudden rise in blood glucose after a meal.
• Cinnamon - 1-6g (Ceylon cinnamon)
• Vinegar - 2x tablespoons
• Green tea - 1-2 cups

The insulin resistant obese / overweight individual needs relieve most urgently, therefore he will also trial fucoxanthin, which has some impressive, but not exactly reliable weight loss data. He will either have a script for metformin or will use alpha lipoic acid (ALA) as a substitute and he will make sure that he gets adequate chromium by taking 200mcg of chromium picoliante or niacin-bound chromium per day *if this is not already in a multi he or she is taking.

The normal-weight insulin resistant individual has slightly different needs than his overweight comrade. He or she is almost certainly suffering from chronic inflammation and beginning or existing NAFLD (the obese will have that, as well, but for him it's only part of the problem). With it's effects on both AMPK and PPAR-gamma berberine will make sure that the body fat levels remain low. Just like taurine (read more), chlorogenic acid (Panchal. 2012) and milk thistle (read more), it will also help "revive" the liver and sooth the inflammation by promoting the bodies own antioxidant defense system.

The cheater, on the other hand, could be everyone who wants to undo (or fore-do, if you will) a high GI carb meal. The ingredients of this stack will ameliorate the blood sugar response and could thus potentially reduce any damage you could do to your pancreas... but let's be honest. With the occasional cheat you are not going to do any damage and if cheating becomes common practice you violate the "lifestyle-changes first!" principle and won't get away healthily no matter how much supplements you take.

Browse previous articles:

Lifestyle Changes

ALA, GABA, Taurine & Co.

Berberine, Banaba & Co.

Cinnamon, Curcumin & Co.

Lemon, Starch, Coffee & Co.

Chlorogenic acid, fucoxanthin & Co.

References:

• Fedor DM, Adkins Y, Mackey BE, Kelley DS. Docosahexaenoic acid prevents trans-10, cis-12-conjugated linoleic acid-induced nonalcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation. Metab Syndr Relat Disord. 2012 Jun;10(3):175-80.
• Huang TH, Teoh AW, Lin BL, Lin DS, Roufogalis B. The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome. Pharmacol Res. 2009 Sep;60(3):195-206.
• Moini H, Tirosh O, Park YC, Cho KJ, Packer L. R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Arch Biochem Biophys. 2002 Jan 15;397(2):384-91.
• Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, Shulman GI. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes. 2006 Apr;55(4):924-8. 
• Panchal SK, Poudyal H, Waanders J, Brown L. Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats. J Nutr. 2012 Apr;142(4):690-7.
• Toomey S, Harhen B, Roche HM, Fitzgerald D, Belton O. Profound resolution of early atherosclerosis with conjugated linoleic acid. Atherosclerosis. 2006 Jul;187(1):40-9. Epub 2005 Sep 22.

Leucine & Phenylalanine Enriched YoYo-Diets Ameliorate Fat Gain, Protect Muscle & Maintain T4→T3 Conversion

Too little leucine & phenylalanine in O.'s diet?

Actually it is quite counter-intuitive that the "YoYo"-diets competitive boydbuilders adhere to (diet vs. bulking phase) are capable of producing such amazing physiques. I mean, when Mr. and Mrs. Average "diet down" and "bulk", the result will usually be neither aesthetic nor healthy, right?

A recent study from the University of Sao Paulo does now provide some insights into the important role the high amount of essential amino acids (leucine and phenylalanine, to be precise) in the typical bodybuilding diets may play with respect to its moderating effects on the lean muscle loss and body fat gains of Opra-esque ups and downs in body weight.

Leucine + Phenylalanine + diet and refeed = ???

I guess the details in the headline to this paragraph are not actually detailed enough to get an idea of what Donato Jr. et al did in their latest rodent study, are they? I see. I will still try to stick to the most important facts.

Contrary to the beliefs of many mostly female victims of life-long dieting, never eating to satiety is NOT going to promote a bikini body - quite the contrary (learn more)

Donato and his colleagues fed a group of adult Wistar rats diets that differed only in their amino acid make-up. Both the control and the experimental diet were based on the same synthetic standard chow (remember what you've learned about synthetic chow lately?). What was different, though was the form of protein / amino acids the scientists used to replace 8.55g of the cornstarch (per kg) of the original diet. The final diets did thus contain either...

• 8.55g of casein (control), or
• 5.45g l-leucine + 3.1g l-phenylalanine (LP)

... as replacements for the cornstarch. Since both were still isocaloric and had an identical protein content (12%) this modification would allow Donato et al. to see if the different amino acid profiles would have nay effects on the weight development of the rodents.

I guess by now you may be asking yourself about the connection to Oprah and boydbuilding diets, right? Well, the 28-day experiment actually had 2 phases a dieting and a maintenance phase. Both cycles were 14 days long. In the first one, the rodents dietary intake was cut in half, while they were allowed to eat as much as they wanted (ad-libitum feeding) in the second 14-day cycle.

YoYo or not - is that the question?

Now, what would you guess happened? I mean, remember: Both diets had an absolutely identical amount of calories and protein - so, the rodents in both groups "hit their macros", right? The logical answer - at least to an increasingly popular, but over-simplistic dietary paradigm - must be: "Nothing! Both groups will end up at an identical body composition.", right!? A brief glance at the data in figure 1 does however suffice to tell you the IIFYM prognosis was not exactly correct - at least not if we take the changes in body composition into account.

Figure 1: Effects of weight cycling with casein (control) and leucine + phenylalanine (L+P) on body composition (left), feed efficiency (=how much weight do you gain per gram of food) and weight (Donato Jr. 2013)

So what can we conclude based on the results in figure 1? Firstly, the small figure on the bottom right goes to show you that weight cylcing per se does not make you "heavy" as in "having a higher BMI than somebody who does not weight cycle". The large figure on the left, on the other hand informs us that weight cycling can cost you muscle and make you fatter - 4% fatter to be precise. Skinny fat, so to say. Notwithstanding, the data from the Donato Jr. study does also tell us that the provision of a low amount of additional leucine and phenylalanine minimized the fat gain in the bulking phase and had beneficial effects on amount of lean mass the rodents maintained and build during the 4-week study. The net result is a higher body weight in the L+P group, at an almost identical body composition.

Leucine + phenylalanine also blunt the reduction of T4 → T3 conversion

If we look closer we do yet see another related, but non-negligible advantage: The typical downregulation of the conversion of the "inactive" thyroid hormone T4 to the "active" thyroid hormone T3 in response to long-term dieting was significantly reduced by the provision of leucine and (I will just go on a limb here and say "more importantly") the neurotransmitter precursor phenylalanine.

Figure 2: Effect of weight cycling of markers of glucose and thyroid metabolism (Donato Jr. 2013)

This did yet not translate into a significant amelioration of the highly significant (>50%) deterioration of the blood glucose metabolism, and the triglyceride levels (not shown) were actually 20% lower in the casein yoyo group (CON) than in the non-weight cycled control group. From a health perspective, the addition of leucine and phenylalanine is thus "only" useful, because it will help you retain or actually build muscle mass (with the data we have, it's difficult to say which effect was the dominant one, but I'd suspect it's the anti-cabatolic one).

Bottom line: You need to be careful about mis- and over-interpreting the results of the study at hand - and that's not just because it's "only a rodent study".

If there was one "take home message" from the study at hand, I guess it would be very similar to the one from the one of the December 2012 post I borrowed this figure from: "Make sure to get at least 10g of EAA with each of your meals"... ah well, "... and avoid 'classic' YoYo dieting à la Oprah, whenever possible - of course!" ;-)

The alleged "lean mass gains" on the L+P diet come at the expense of a non-negligible increase in body fat. Overall the lean mass to fat mass ratio is thus not better than in the continuously fed rodents. And unless your beauty ideal is all about being "massive", this is not necessarily going to be an improvement to your physique.

If you take another look at figure 1 you will also see that the feed efficiency, i.e. the amount of weight you gain per kcal you consume was not reduced but increased by the addition of leucine and phenylalanine. This may be a result of the pro-insulinogenic and "anabolic" (Nuttall. 2006; Iverson. 2013), as well as the anti-cabatbolic effects of these amino acids and is thus not necessarily "bad".

It would nevertheless be highly unwarranted to believe that supplementing your diet with leucine + phenylalanine on a a "lean bulk" would yield significant advantages - this hypothesis is clearly not supported by the study at hand. The same goes for the usefulness of supplementing isolated amino acids, in this case leucine and phenylalanine, on top of a high protein diet, in general. In fact, I can refer you directly to an older article of mine that confirms that you better make sure to get the full dose of 20g+ of whole protein than trying to make up for it by adding additional aminos (learn more)

References:

• Donato, J. et al. Effects of leucine and phenylalanine supplementation during intermittent periods of food restrictionand refeeding in adult rats. Life Sciences. 2007 [epub ahead of print]
• Iverson JF, Gannon MC, Nuttall FQ. Ingestion of leucine + phenylalanine with glucose produces an additive effect on serum insulin but less than additive effect on plasma glucose. J Amino Acids.
• Nuttall FQ, Schweim KJ, Gannon MC. Effect of orally administered phenylalanine with and without glucose on insulin, glucagon and glucose concentrations. Horm Metab Res. 2006 Aug;38(8):518-23.

Science Round Up Seconds: Are Statins Good for Your Brain? Have the Scientists Just Forgotten About the Risks?

Brainy question of the day: Will statins revive or criple your brain?

Those of you who made it in time for yesterday's live-show, will already know that I have "postponed" publishing the (by then) commented list of dietary supplements to improve and maintain insulin sensitivity to Sunday.

It was my original plan to publish this list along with three suggested supplement stacks on Sunday and sticking to it has the advantage of a "true" ending to the "Maintain and Improve Your Insulin Sensitivity" series (read previous posts) - there is already enough chaos among the 1351 published SuppVersity posts ;-).

Furthermore, it will unquestionable be good for your brain, if I do not flood it with an informational overload by trying to cram all the information about the insulin sensitizers, as well ;-)

Download!

Don't forget to download the podcast: If you have not already done so, I suggest you download and listen to the show. With Carl's questions and comments the radio show does also deliver some extra information that is not part of this summary.

I have to admit that I must have over-read the original article a listener who goes by the name "Rad Fox" referenced in an email he send to onair@superhumanradio.com (feel free to bother us with questions for future episodes). In this email "Rad" referenced an article which turned out to be one of these notorious copy + paste pieces of a press release. The latter came from John Hopkins Medicine and discussed the results of an as of now unpublished paper about the incidence of dementia in patients on statin therapy.

This is not the first review that connects statin use to brain health!

Despite their bad reputation within the health and fitness community, the use of statin drugs has in fact been shown in numerous studies to keep your brain on top of the game. Another very recent meta-analysis of data from studies with 2851 cases and 57020 participants, for example, says that statin use is associatied with a statistically significant -48% reduction in dementia risk (Song. 2013). Similarly, Steenland et al. write in a paper that's been published roughly a month ago:

"Research volunteers with normal cognition at baseline evaluated an average 4.1 times over 3.4 years (1,244 statin users, 2,363 nonusers) and with mild cognitive impairment (MCI) at baseline evaluated an average 3.9 times over 2.8 years (763 users, 917 nonusers)." (Steenland. 2013)

Irrespective of the high number of empirical studies that seem to support the efficacy of statins as "anti-dementia" drug, I did not even have to bother with PubMed or any other medical database to find trials that suggest that the use of statin drugs will have the exact opposite effects. I just had to scroll down to the end of the article, where I found a news report on an study that claims that Pravachol, obviously likewise a statin drug, would be "linked to memory impairment" (read the news story).

Beneficial or detrimental? Which results can you trust?

Your body does in fact produce i's own anti-dementia "drug": Melatonin. With the natural decline of the metlatonion production with age, it is thus only logical that you develop dementia, only in your older age - learn how to protect yourself with melatonin

I know it can be enervating at time, but it's one of the central characteristics of science that it's results are usually ambiguous and far from achieving the status of "undebatable truths". If you've been around the SuppVersity for some time now, you should by now have overcome this naive understanding of the nature of science by now, anyways.

"The promising results obtained in vivo and in epidemiological studies are generally not in accordance with those of placebo-controlled randomized clinical trials." (Silva. 2013)

You should also be aware that the best way to reconcile these discrepancies between epidemiological and experimental evidence is to identify the underlying mechanism behind the effects statins exert on the build-up of neuronal plaque. As soon as we know exactly what's happening we may well be able to decide whether the protective effects we see are "real" or just an "epidemiological Fata Morgana".

The most important question we have to answer is: "HOW?"

Unless we have a rationale explanation for the protective effects statins may have on the brain of (elderly!) individuals, we can file the claim "statins protect elderly brains against cognitive decline" in the "still to be investigated" folder and let it rest there until we have a verifiable theory (= sum of hypothesis) to explain how the use of a drug that was originally designed to block the endogenous production of cholesterol could have such an effect on the brain.

Dietary vs. endogenously produced cholesterol: I know that most of you will be aware that statins reduce your bodies own (=endogenous) production of cholesterol. Most of you will probably also know that it is this endogenously produced cholesterol that is - if any form of cholesterol - to be held responsible for coronary heart disease and (purportedly) the formation of plaque in the brain.

If you are not a narrow-minded text-book physician, you will have to acknowledge that eggs promote an anti-artherogenic cholesterol profile and will thus probably have anti-Alzheimer's and anti-dementia effects (learn more)

For the average human being, his dietary cholesterol intake will have no or only minor influence on the serum levels of cholesterol and cholesterol rich foods such as eggs, have actualle been found to exerd positive effects on the cognitive function of elderly individiuals (Aparicio. 2013); and despite the fact that the results did lose their significance, when they were stratified for total energy intake and education level, the Aparicio study should remind us that the role cholesterol rich foods do not necessarily increase your dementia risk, even if cholesterol was mechanistically involved in the etiology of dementia - even if studies in rodents and rabbits who were fed with synthetic high cholesterol diets suggest otherwise (learn more about the problems with synthetic diets).

And what about saturated fat? In a study from Japan (the Hisayama Study; cf. Ozawa. 2013), the consumption of a diet with a normal amount of saturated fat in it and not the allegedly healthier "almost zero SFA" pattern were associated with reductions in all cause (-34%), Alzheimer's (-35%) and vascular dementia (-55%) - a direct negative effect of saturated fats is thus unlikely. A negative impact of certain foods that happen to have a high amount of saturated foods in them, on the other hand, cannot be excluded.

The most straightforward explanation for the beneficial effects scientists observed in numerous epidemiological studies would obviously be a direct one: "Statins take away a substrate that's necessary for the amyloid plaque to form." This hypothesis would also be supported by significant correlations between elevated serum cholesterol levels and plaque build-up in the brain, as they were observed by (among others) by Matzusaki et al. in who used the same cohort Ozawa et al. analyzed in their study on the influence of certain dietary patterns on the risk of developing dementia (see red box above). In the corresponding paper Matzusaki et al. report:

Table 1: Official "normal" levels for total, LDL & HDL cholesterol, as well as triglycerides (based on AHA recommendations)

• 23x higher risk for total cholesterol > 5.8mmol/L
• 13x higher risk for LDL > 4.02 mmol/L
• 70% higher risk for HDL < 1.04 mmol/L (p > .5)
• 3.5x higher risk for triglycerides >1.56mmol/L
  that's compared to Q1 <0.51mmol/L
• 7x higher risk for LDL / HDL > 3.48 mmol/L
• 3.1x higher risk for “non-HDL” > 4.61 mmol/L

What makes Matzusaki et al.'s observation particularly interesting is the fact that they are based on 147 autopsies that were performed between 1998 and 2003. Autopsies? Yes, I know that sounds gross and irrelevant, but it has the advantage of

• being able to measure the amount of plaque directly,
• having physical and quantitative data, and
• not being limited to diagnosed cases of dementia.

In other words: Your data is not going to be skewed by analyzing only those who are already sick enough to be treated, when you are able to look at the brains of a representative sample of the population after they died.

Dead or alive, there is more than one hypothesis

Remember: We are inclined to forget that the only difference between "effects" and "side effects" is our assessment of the latter. The beneficial effects statins have on the expression of AGE receptors, for example would be  "side effects" for a classic statin which is obviously supposed to lower cholesterol and nothing else. In the context of dementia prevention, this side effect it is the intended effect and the cholesterol lowering effects of statins are the "side effects".

In view of the myriad of already discovered and hitherto undiscovered "side effects" of statins it is however just as likely that the reduced dementia risk is a result of  ...

• a reduction in advanced glycation end product receptors in the brain and thus a protection against the negative effects AGEs exert on the brain (Liu. 2012; Deane. 2012).
  On a side note: If you want to counter the production of endogenous AGEs you can do so with taurine (Nandhini. 2004). This would obviously render the use of a statin to reduce the receptor density obsolete.
• a blockade of the “maturation” from plague precursors to amyloid beta plaque (Hosaka. 2013)

... or a combination of all these effects with the direct and indirect role cholesterol plays in the formation of plaque in the brain (Fantini. 2013; Hung. 2013).

Whether we will ever really know that it is that appears to protect statin users from dementia is thus obviously still anybody's guess. What is not "anybody's guess" is whether it makes sense to take a statin solely to protect yourself from developing dementia. That would - in my humble opinion - rather be a sign of existing cognitive decline than a protection against its development ;-)

Bottom line: Despite the fact that I have never been a statin advocate it is difficult to argue with the current epidemiological evidence: People who take statins have a lower incidence of dementi *fullstop* Whether this is even related to cholesterol is however as questionable as Carl's suggestion that it's an overall reduction in inflammation as it has been observed by Reis et al. (2012) in the context of Malaria infections, where statins appear to be able to sooth the "brainflammation" that's behind the beneficial effects of statin drugs.

Those who take statins can benefit from eating pomegranate | learn more

What is more or less undebatable, though, is that "there is insufficient evidence to recommend statins for the treatment of dementia" (McGuinness. 2013). I will leave you with this conclusion from the latest Cochrane review and a discreet reference to the influence of APO-E phenotypes on both baseline cholesterol levels and the development of Alzheimer's disease. Who knows? If we controlled for the APO-E4 allele, we may well find that carriers of the AA (=2x positive) form of the APO-E4 gene, of which a recent study from the University of Toronto suggests that having this homozygous APO-E4 gene poses a 56.0x higher risk (no typo!) of developing dementia (all forms), benefit from taking a statin while others don't? I will obviously keep you posted on all future developments.

References: 

• Aparicio Vizuete A, Robles F, Rodríguez-Rodríguez E, López-Sobaler AM, Ortega RM. Association between food and nutrient intakes and cognitive capacity in a group of institutionalized elderly people. Eur J Nutr. 2010 Aug;49(5):293-300.
• Barberger-Gateau P, Letenneur L, Deschamps V, Pérès K, Dartigues JF, Renaud S. Fish, meat, and risk of dementia: cohort study. BMJ. 2002 Oct 26;325(7370):932-3.
• Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S, Paquette N, Deane RJ, Thiyagarajan M, Zarcone T, Fritz G, Friedman AE, Miller BL, Zlokovic BV. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest. 2012 Apr 2;122(4):1377-92. 
• Fantini J, Yahi N, Garmy N. Cholesterol accelerates the binding of Alzheimer's β-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation. Front Physiol. 2013;4:120. doi: 10.3389/fphys.2013.00120.
• Liu R, Wu CX, Zhou D, Yang F, Tian S, Zhang L, Zhang TT, Du GH. Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE)-independent signaling pathways and regulating mitochondrion-mediated apoptosis. BMC Med. 2012 Sep 18;10:105. 
• Hosaka A, Araki W, Oda A, Tomidokoro Y, Tamaoka A. Statins reduce amyloid β-peptide production by modulating amyloid precursor protein maturation and phosphorylation through a cholesterol-independent mechanism in cultured neurons. Neurochem Res. 2013 Mar;38(3):589-600.
• Hung YH, Bush AI, La Fontaine S. Links between copper and cholesterol in Alzheimer's disease. Front Physiol. 2013;4:111. 
• Matsuzaki T, Sasaki K, Hata J, Hirakawa Y, Fujimi K, Ninomiya T, Suzuki SO, Kanba S, Kiyohara Y, Iwaki T. Association of Alzheimer disease pathology with abnormal lipid metabolism: the Hisayama Study. Neurology. 2011 Sep 13;77(11):1068-75.
• Nandhini AT, Thirunavukkarasu V, Anuradha CV. Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine. Acta Physiol Scand. 2004 Jul;181(3):297-303. 
• Ozawa M, Ninomiya T, Ohara T, Doi Y, Uchida K, Shirota T, Yonemoto K, Kitazono T, Kiyohara Y. Dietary patterns and risk of dementia in an elderly Japanese population: the Hisayama Study. Am J Clin Nutr. 2013 May;97(5):1076-82.
• Reis PA, Estato V, da Silva TI, d'Avila JC, Siqueira LD, Assis EF, Bozza PT, Bozza FA, Tibiriça EV, Zimmerman GA, Castro-Faria-Neto HC. Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria. PLoS Pathog. 2012 Dec;8(12):e1003099.
• Silva T, Teixeira J, Remião F, Borges F. Alzheimer's disease, cholesterol, and statins: the junctions of important metabolic pathways. Angew Chem Int Ed Engl. 2013 Jan 21;52(4):1110-21.
• Song Y, Nie H, Xu Y, Zhang L, Wu Y. Association of statin use with risk of dementia: A meta-analysis of prospective cohort studies. Geriatr Gerontol Int. 2013 Mar 6.
• Steenland K, Zhao L, Goldstein FC, Levey AI. Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment. J Am Geriatr Soc. 2013 Sep;61(9):1449-55.

Cholorgenic Acid, Fucoxanthin and Irvingia Gabonensis - Supplements to Improve & Restore Insulin Sensitivity #4.1

In case you are wondering about the potatoes on the bottom right - they shall remind you that the caffeic acid ester is not a prerogative of green coffee beans.

As my buddy Sean Casey from www.caseperformance.com let me know I did actually overlook three suggestions to the "Maintain & Improve Your Insulin Sensitivity" series I had promised to include (sorry Tom!). Well, I am a man of my word and will make good for that today.

Before I begin discussing chlorogenic acid, fucoxanthin and irvingia gabonensis, I do just briefly want to point out that I deliberately postponed this post to Thursday, because it fits in quite nicely with one of the two hot topics of today's installment of the SuppVersity Science Round-Up on the Super Human Radio Network [brace yourselves, some sleazy self-promotion is about to follow ;]

The Science Round-Up airs every other Thursday, 12PM (EST)

SVSR - Sneak Peak: Airing at 12PM (EST) is today's installment of the SuppVersity Science Round-Up (listen live!). Scheduled topics for today are (1) "Are statins protecting us from Dementia? I thought it was the other way around!" - a discussion of the recent mainstream media news on "breakthrough science" and (2) a summary of the most interesting agents from the "Maintain & Improve Your Insulin Sensitivity Series" (read it). The latter will include a list of supplements that can be used to improve your insulin sensitivity and a discussion of the important and often overlooked question: "Which supps work for whom?"

Ok, that's it for the "advertisment break" ;-) Let's get back to the science of supplemental insulin sensitivity improvements. What works, what doesn't?

• Chlorogenic acid [A]: Actually I did not really overlook chlorogenic acid, I did only forget to mention that I would not discuss it on its own, because it is one of the main active ingredients in coffee. In fact it is one of those that are held responsible for effects such as those Kelly L Johnston and her colleagues observed in a 2003 study on the effects of coffee consumptions on the release of gastrointestinal hormone and glucose tolerance in humans (Johnston. 2003).
  
  What the scientists observed in their 9 healthy fasted volunteers who consumed 25 g glucose in either 400 mL water (control) or 400 mL caffeinated or decaffeinated coffee (equivalent to 2.5 mmol chlorogenic acid/L) a decade ago stands in line with the results of more recent studies that confirm that cholorogenic acid, which can also be found in herbs like dandelion and a whole host of other foods, like potatoes (10-14mg/100g; Dao. 1992), or broccoli (60mg/kg; Clifford. 2000), has potent anti-diabetic effects of which Ong et al. found only recently that they are - how else could it be - mediated by the activation the metabolic fuel gauge AMPK (Ong. 2013).
  
  Now all that would suggest that chlorogenic acid was an "A", as in "all of you should at least drink plenty of coffee", but if it was just for the chlorogenic acid content of the dark brew, a recent study by Mubarak et al. does actually question whether this may not have the exact opposite effect.

  

  A recent study on CGA supplementation with high fat diets raises a huge questionmark wrt to the effects of CGA on body fatness and - even more so - insulin sensitivity (Mubarak. 2013)

  As you can see in the figure above, the researchers from the University of Western Australia made an observation that stands in stark contrast with the results presented by Ong et al. earlier this year. The co-administration of a "physiologically obtainable dose" (1 g/kg of diet) of chlorogenic acid as part of the high fat diet the mice in the study were exposed to lead to a down-regulation of AMPK in the liver and, subsequently, an increase in NAFLD risk (learn more about the connection between NAFLD and diabetes).
  
  

  

  Effects of 329mg of CGA on substrate oxidation after determined during 3h postprandial phase (Soga. 2013)

  The underlying reasons of this discrepancy will still have to elucidated and I want to emphasis that they stand in conflict with evidence from both epidemiological studies and controlled trials (Vinson. 2012). The most recent of the latter is a paper by Soga et al. which confirms that the supplementation of a beverage containing 329 mg of chlorogenic for 4 weeks will increase both the postprandial energy expenditure (+5% vs. control) and fatty acid oxidation (+5% vs. baseline) in - and this is important - 16 healthy normal weight guys with a BMI of ~22kg/m² and a body fat percentage of only 16.7%.
  
  While it will have to be elucidated whether the negative effects Mubarak et al. observed in their recent study are related to the metabolism of CGA by different bacteria in the gut (cf. Nicolson. 2005) or specific dietary co-factors, cholorogenic acid still deserves an "A", as in "almost certainly beneficial". The suggested dosage for an adult is somewhere between 200-1,000mg/day and it is best taken with foods. This is particularly true if you get your cholorogenic acid from some sort of an extract (e.g. green coffee bean). These often contain other agents that are not exactly easy on your digestive tract. 
• Fucoxanthin [A-]: It has the word "thin" in it and has actually some promising data as a weight loss adjuvant. At first it looks as if it was "just" another powerful anti-oxidant with second / third line effects on insulin sensitivity that are mediated by an amelioration of whole body inflammation and as of now somewhat dubious weight loss effects. If we go beyond the few non-sponsored human trials and include the results of in-vitro studies, it does yet appear, as if fucoxanthin could also exert direct effects on your insulin sensitivity. The mechanisms?
  

  • 

    6-gingerol is probably a more reliable PPAR-gamma antagonist and it is only one out of 20 agents I discussed in a previous article - alongside vitamin A, curcumin, resveratrol, artimesia, glucosamine, and co.

    Fuco reduces the glucose uptake in mature fat cells (PPAR-gamma blockade), and facilitates the growth on new ones (Kang. 2011). Ok, that's not beneficial for someone who does not intend to remain fat, but it would allow you to become a "healthy obese" individual, who have a high number of small fat cells. In the presence of a caloric deficit, when new fat cells are not going to be formed it could also have a repartitioning effect.
  • Foco increases muscular GLUT-4 expression and interacts with PGC1-alpha; this is something you will usually see after a workout - not bad right (Kang. 2012)?
  In conjunction with its purported anti-cancer, antioxidant, anti-inflammatory, antiangiogenic and antimalarial activities (Peng. 2011), it may sound as if Fuco was a definite "A" as in "all of you should be on it", but with the few and not exactly extremely credible human trials, I am not willing to award more than a "B" as in "B-uy if you got money to spare and want to try something new". Why? Well, I don't have to tell you that you are the ones who constantly remind me that "rodents are no little men" - 99% of the subjects in the few existing in-vivo studies were however just that: rodents. The available information on optimal dosing regimen is correspondingly scarce and the best I can say is that sponsored studies on combination products suggests that 1.5-3.0mg per day would be necessary to actually see results, my calculation based on a rodent study by Jeon et al. (2010), on the other hand, says that you'd need ~16mg per day.
• Active ingredients, standardization and extracts While this does not apply for irvingia supplements only, the use of a specific (patented) extract in the Ngondi study reminds me to remind you that ostensibly identical products with say 200mg of irvingia in it may well have totally different effects. This is the case for irvingia and all other herbals, for which we do not really know the active ingredients and you cannot - even if you wanted - produce a standardized extract.
  

  Similarly, any 1:10 extract can - in the worst case - be less potent than the raw material, if the active ingredient was lost or at least significantly reduced during the extraction process. Keep that in mind, whenever you shop for herbal supplements.
  Irvingia gabonensis [B]: The number of human studies for irvingia is similarly low as for many of the other hyped anti-obesity drugs and looking at the few credible studies we do have it does not appear as if the seed extracts from the traditional West African food plant would have any direct effect on glucose management.
  
  In a 2009 study by Ngondi et al., for example, the adminstration of 150mg of a standardized irvingia extract did lead to impressive weight and "waist loss" of 12.8kg and 17cm in only 10 weeks. The corresponding reduction in fasting blood glucose is however a result of the weight loss and not vice versa. In other words, irvingia, which appears to act on both PPAR-gamma and leptin (Oben. 2008), improves glucose metabolism by reducing body fat (if we believe what the few existing studies are telling us)
  
  In view of the fact that irvingia works its still under-researched weight loss magic via leptin- and not insulin / blood glucose related mechanisms, irvingia gabonensis is only a "C" as in "C-an be used to get rid of body weight" (I would not put too much faith into the results of the existing studies, by the way). What appears to be quite certain, though, it that irvingia doe not have any direct insulin sensitizing effects - at least none that have been reliably documented in peer-reviewed studies. In addition, it is highly questionable that the next best supplement you buy will have a similar active ingredient composition as the IGOB13 (patented) extract that was used in the study by Ngondi et al.

So, these were the items that were missing from the previous installments of the "Maintain and Increase Your Insulin Sensitivity" series (read all articles).

Come back for more! The complete summary with some more general comments and three suggested stacks is going to be up next Sunday, as planned.

If you do not want to wait for that, I highly suggest you listen to the live show today at 12PM (EST) or download the podcast from the SuppVersity Science Round-Up: Seconds tomorrow.

References: 

• Clifford, MN, Chlorogenic acids and other cinnamates: nature, occurrence, dietary burden,
  absorption and metabolism. J. Sci. Food Agric. 2000, 80, 1033–1043
• Dao L, Mendel F. Chlorogenic acid content of fresh and processed potatoes determined by ultraviolet spectrophotometry. Journal of Agricultural and Food Chemistry. 1992; 40(11): 2152-2156.
• Jeon SM, Kim HJ, Woo MN, Lee MK, Shin YC, Park YB, Choi MS. Fucoxanthin-rich seaweed extract suppresses body weight gain and improves lipid metabolism in high-fat-fed C57BL/6J mice. Biotechnol J. 2010 Sep;5(9):961-9.
• Johnston KL, Clifford MN, Morgan LM. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr. 2003 Oct;78(4):728-33. 
• Kang SI, Ko HC, Shin HS, Kim HM, Hong YS, Lee NH, Kim SJ. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes. Biochem Biophys Res Commun. 2011 Jun 17;409(4):769-74.
• Mubarak A, Hodgson JM, Considine MJ, Croft KD, Matthews VB. Supplementation of a high-fat diet with chlorogenic acid is associated with insulin resistance and hepatic lipid accumulation in mice. J Agric Food Chem. 2013 May 8;61(18):4371-8.  
• Ngondi JL, Etoundi BC, Nyangono CB, Mbofung CM, Oben JE. IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation. Lipids Health Dis. 2009 Mar 2;8:7. 
• Oben JE, Ngondi JL, Blum K. Inhibition of Irvingia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARgamma and leptin genes and up-regulation of the adiponectin gene. Lipids Health Dis. 2008 Nov 13;7:44.
• Ong KW, Hsu A, Tan BK. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation. Biochem Pharmacol. 2013 May 1;85(9):1341-51.
• Soga S, Ota N, Shimotoyodome A. Stimulation of postprandial fat utilization in healthy humans by daily consumption of chlorogenic acids. Biosci Biotechnol Biochem. 2013 Aug 23;77(8):1633-6. 
• Peng J, Yuan JP, Wu CF, Wang JH. Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health. Mar Drugs. 2011;9(10):1806-28.
• Vinson JA, Burnham BR, Nagendran MV. Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes. 2012;5:21-7.

Obesity Negates Glucose Sensitizing Effects of Resistance Training. Lifting Works Only For Normal Weight Women

The results of the study at hand clearly suggest: There is no single ideal type of exercise; plus: What's optimal may change when your health / physique changes

"You got to exercise!" When the average overweight patient hears these words coming out of the mouth of his doctor, the type of exercise he usually will be thinking about is "classic" steady state cardio training on a treadmill, elliptical, stairmaster, or ergometer.

It's the textbook approach and still the predominant form of exercise in most of the pertinent studies on nutrition + exercise interventions that are designed to help overweight / obese individuals shed weight and improve their health.

Among the (usually) non-obese and rarely insulin resistant members of the health and fitness community this type of "cardio training" (LISS) has however gotten quite a bad rep as of late.

More and more trainers suggest that it may bet better to lift weights and do the occasional HIIT sessions for everyone - irrespective of your body weight, health and training status. If we put some faith into the results of a recently published study from the University of Massachusetts this could eventually turn out to be another unwarranted over-generalization that disregards the very specific needs of lean vs. obese and insulin sensitive vs. insulin resistant individuals.

Don't forget you are "evolving": Your journey from fat to fit will not simply change the way you look and feel, it will also have a direct impact on the optimal workout and nutrition regimen for you. Consider it your personal "evolution" that may well start out with a no-carb + endurance approach and "evolve" into a medium-to-high-carb + resistance training approach over the years.

Much contrary to the idea that there must be a perfect way to exercise, Steven K. Malin and his colleagues started out with the hypothesis that

"[...] excess body fat would attenuate the improvement in insulin sensitivity and reduction in glucose-stimulated insulin secretion after acute and chronic resistance exercise" (Malin. 2013)

In other words: The same type of exercise that may be highly beneficial for a lean / normal-weight individual could be absolutely ineffective for his overweight neighbor; and if that were the case, this would at least partly explain why some of the studies in obese individuals suggest that regular strength training would not be a match for the arduous light intensity steady stead training (LISS) approach to fitness.

Despite the fact that the corresponding control group on a LISS regimen was missing in the study at hand, the results Malin et al. present in their soon-to-be-published paper would in fact support just that: As long as you are still fat, weight training may be a good way to maintain lean body mass, but not the appropriate form of exercise to get your blood sugar problems and other health issues under control.

Body fat and pumping iron don't groove

The subjects of the Malin's study were 26 young women (21.2±0.7 years) who ere randomized to either a control or intervention group.

Potential explanation of the phenomenon: In the obese the increase in free fatty acids due to the "stressing" (=sympathetic nervous system activity) effects of weight lifting may impair / reverse the exercise induced increase in glucose uptake.

Weights don't work for HDL, either! The beneficial effects of resistance training on HDL are blunted by obesity, too (Nicklas. 1997; study in men).

While the women in the control group had to do nothing but be their lazy sedentary selves, the (un?)lucky girls in the intervention group performed a classic progressive resistance training (PRT) with the following characteristics:

• fully supervised exercise sessions 
• 3 days/week for 7 weeks
• workout duration ~60 min/session 
• intensity 60 % 1-RM
• 3 set of 8-12 repetitions
• 90-120s rest between sets
• 5-10 min of stretching before + after

Otherwise the women in the strength training arm of the study were instructed to maintain habitual physical activity and diet habits throughout the study...

... with one exception, though: On the day before the metabolic testing sessions, they were yet advised to consume a standardized mixedmeal diet with 55% carbohydrate, 30% fat, 15% protein.

Figure 1: Changes in glucose metabolism in response to exercise intervention (Malin. 2013)

With the standardized diets, it was thus not possible that the results in figure 1 (no improvement in insulin sensitivity in the obese women with a mean body fat percentage of 48.2%) were corrupted by crazy candy feasts on the day before.

Could "cardio" really be more than just a necessary evil on your way to a physique like this? (learn more)

So is it weight loss before weights, then? While it is true that there are no direct beneficial effects of resistance training on insulin sensitivity in the obese, you would be ill advised to skip it all together.

Let's assume you can train four times a week. In that case you could progress from a 3:1 to a 1:3 endurance-to-resistance-training-ratio as you journey from obese to normal weight and insulin resistant to "normal" (you can also use a 2:1 LISS : HIIT ratio, but keep in mind that HIIT hits the sympathetic CNS, as well).

It is also possible to combine both, cardio and weights - specifically if you belong to the group of trainees who lack minimal strength (you can't do 10 push ups) and endurance (you cannot jog casually for at least 15min).

References: 

• Malin SK, Hinnerichs KR, Echtenkamp BG, Evetovich TK, Engebretsen BJ. Effect of adiposity on insulin action after acute and chronic resistance exercise in non-diabetic women. Eur J Appl Physiol. 2013 Sep 27.
• Nicklas BJ, Katzel LI, Busby-Whitehead J, Goldberg AP. Increases in high-density lipoprotein cholesterol with endurance exercise training are blunted in obese compared with lean men. Metabolism. 1997 May;46(5):556-61.

Periodization Techniques Revisited: Improved Strength & Size Gains W/ 12-Week Undulatory vs. Linear Periodization

There is going to be a point in everyone's training career, when 100 push-ups a day alone are no longer going to "cut" it and you got to to modify and later periodize your training to keep making progress.

Ah, that feels so good... No, not what you are thinking, now. I am sitting at my desk - alone, no female White House intern around ;-) Still, it's simply nice to see another study with real-world relevance for the average and not so average trainee.

The study comes from the Federal University of Rio de Janeiro and was conducted by Juliano Spineti and colleagues. The Brazilian researchers compared two periodization models: Linear periodization, which probably what most of you will have been starting out with what the scientists consistently (mis-)label  as "ondulatory periodization", a training method of which you will soon realize that you may be more familiar with it's fundamental principles than it may seem initially.

"Ondulatory periodization?"

I have to admit I was confused at first. I mean, I am the last person to complain about typos, so I willingly accepted that the scientists must have made a mistake in the abstract. When I downloaded the full text to the study and found that they stuck to "ondulatory" instead of "undulatory" periodization, I did however begin to question, whether this may in fact be a new twist to the good old undulating periodization, which is based on the hypothesis that changing reps, volume and intensity from one workout to the other (Table 1, left + red) would yield more beneficial results than the classic 4-week cycles.

Table 1: Undulating (left) and linear (right) periodization prgram used in the study at hand (Spinetti. 2013)

Apropos classic. I guess this is what everyone of you will be thinking of, when they hear about periodization. It's also part of the so called HST (=Hypertrophy Specific Trainting) routines and has you change the set and rep-ranges, intensity, rest times etc. on a monthly basis. In that, the order is usually as follows: "Resistance" (usually this is called "strength endurance"), "hypertrophy", "maximal strength" → repeat...

Suggested Read: "Periodization, Yeah! But How? " | read more

Don't forget that there is more to periodization than changing up your set/rep/intensity... no idea what that could be? Well, what about detraining or tapering? Taking some time off is about as important as hitting it hard. Unfortunately this simple wisdom is ignored by the majority of trainees who love to hit it hard, but hate and/or refuse to take it easy for some time - no matter how beneficial that may be (learn more).

If you look at the left-hand side of table 1 you will realize that the "misnomer" of the "strength endurance phase" which is called "resistance" in the Spinetti study is the only thing that would point towards an innovative training protocol and away from a simple typo in "ondulatory"... a typo that is repeated 5+ times within the full-text though :-/

Typos, but intriguing results

If we still put some faith in the results the 32 men from the Brazilian Marine corps (26 years, 15% body fat),  who were advised to refrain from any additional physical activity during the trial achieved, we'd have to follow the researchers' very own conclusion that the undulatory training regimen would make a better choice - at least for the average, lean, physically active individual who is starting his or her first resistance training regimen in the gym.

Figure 1: Effect sizes of 12 weeks tranining with undulatory (OP; remember the typo ;-) and linear (LP) periodization on 1RM strength, maximal voluntary contraction force (MVC) and muscle thickness (Spinetti. 2013)

Both the effect sizes (left, 3D) and the absolute values (right; muscle size only; 2D) clearly speak in favor of the more versatile undulatory training regimen.

Intra-workout periodiziation inspired by Dr. Squat: Some of you will already know that I personally like to train in a way that is based on a concept by Hatfield (Dr. Squat) with different rep/rest/intensity patterns within one training sessions.

If you have no idea what this may look like, these two examples may help:

5x5 for squats w/ max. 2min rest (strength); 3x10 for leg presses w/90s rest (hypertrophy) 2x20 for leg extensions w/60s rest (strength endurance)

5x5 for decline bench press w/ max. 2min rest (strength); 3x10 for incline bench press w/90s rest (hypertrophy) 2x20 for cable cross (strength endurance)

The fundamental pattern is compound for strength, basic for hypertrophy, stretch / pump exercise for strength endurance.

Linear periodization no more?If you look at the study data it is obvious that undulatory training makes you stronger, allows for faster muscle growth and... well, that's not in the study, but once you try it you will realize it, it's much more fun, as well. So why bother with linear periodization any longer? Well, the reason should be obvious: This is a single study the result of which are

• supported by Rhea et al. (2002), Monteiro et al. (2009), Prestes (2009), Miranda et al (2011)  and Simao (2012), but
• refuted / questioned by Baker et al. (1994), Bufford et al. (2007) and Kok et al. (2009),

who report identical gains in strength and size in 22strength and power in experienced male athletes (Baker. 1994), 26 recreationally trained college-aged male and female (Bufford. 2007), and 20 untrained but fit women (20yr, normal weight) (Kok; 2009).

Personally, I like to dabble with both undulating, but also with intra-workout "periodization" a la "Dr. Squat" (see box to the right) while I hate, and I mean "hate" as in totally detest, these lame 4-week cylces of doing the same stuff every workout. The "I hate ..." argument may not sound as if it would hardly qualify as being "SuppVersity Approved", but it in fact is. I am the last person to suggest you drag yourself to the gym and do something you hate. That's not going to be productive, trust me - no matter what science says, by the way.

References: .

• Baker D, Wilson G, Carlyon J. Periodization: the effect on strength of manipulation volume and intensity. J Strength Cond Res1994;8:235-42.
• Bufford TW, Rossi SJ, Smith DB, Warren AJ.A comparison of periodization models during nine weeks with equated volume and intensity for strength. J Strength Cond Res. 2007;21:1245-50.
• Kok LY, Hamer J, Bishop DJ. Enhancing muscular qualities in untrained women: linear versus undulating periodization. Med Sci Sports Exerc 2009;41:1797-807. 
• Miranda F, Simão R, Rhea M, Bunker D, Prestes J, Leite RD, et al. Effect of linear vs. ondulatory periodized resistance training on maximal and submaximal strength gains. J Strength Cond Res. 2011;25:1824-30.
• Monteiro AG, Aoki MS, Evangelista AL, Alveno DA, Monteiro GA, Piçarro IC, et al. Nonlinear periodization maximizes strength gains in split resistance training Stone routines. J Strength Cond Res 2009;23:1321-6
• Prestes J, Frollini AB, Lima C, Donatto FF, Foschini D, Marqueti R, et al. Comparison between linear and daily undulating periodized resistance training to increase strength. J Strength Cond Res. 2009;23:2437-42.
• Rhea MR, Ball SD, Phillips WT, Burkett LN. A comparison of linear and daily undulating periodized programs with equated volume and intensity for strength. J Strength Cond Res2002;16:250-5.
• Simão R, Spineti J, Salles BF, Oliveira L, Matta TT, Fleck SJ. Comparison between linear and nonlinear periodized resistance training: strength and muscle thickness effects. J Strength Cond Res. 2012;26:1389-95.
• Spinetti J, et al. Comparison Between Different Periodization Models On Muscular Strength And Thickness In A Muscle Group Increasing Sequence. Rev Bras Med Esporte. 2013; 19(4).