Monthly Archives: June 2012

Dark chocolate meets probiotics; the bifidobacteriomance continues

Posted on June 28, 2012 | 9 comments

or the next big thing in functional foods, Op. 84

Altered gut bacteria can cause a whole host of problems, anywhere from depression and fatigue to ADHD and heartburn.  Thus, while running my daily search for “bifidobacteria,” I happened across these little goodies: 

The Attune Foods Dark Chocolate Probiotic Bar.  Combining probiotics (e.g., bifidobacteria, acidophilus, etc.) with chocolate?!  And with 68% cocoa, I’d expect this bar to deliver at least some of the benefits of dark chocolate (e.g., improved insulin sensitivity). They’re gluten-free and even contain inulin! (my second favorite bifidogenic prebiotic.)

And it packs a big, or rather huge, probiotic punch (6.1 billion B. lactis HN019, L. acidophilus NCFM, & L. casei LC-11).  Attune loses a little cred by trying to disguise their sugar as “evaporated cane juice,” like it’s something inherently healthier than plain old sugar… just like all-natural agave syrup, honey, and organic coconut blossom sugar.  just own it for crying out loud.  On the other hand, at only 6 grams, the sugar in Attune’s bar is harmless especially in the context of the high cocoa content, inclusion of inulin, and whopping dose of probiotics.

But, chocolate & probiotics?  Alas, the curiousity bug had bitten.

Apparently, a lot of companies think dark chocolate is a good vehicle for probiotic delivery.

GI Health’s Probiotic Chocolate is gluten-free and contains a half billion L. helveticus R0052 and B. longum R0175 per serving.  A half-billion is low by conventional standards*, but such standards might be irrelevant if the delivery vehicle (i.e., chocolate) is superior.

*Most probiotic products are rated (by me) by the number of live bacteria per serving, or “colony forming units (cfu).”  This is usually in the billions because most die in transit, thus the importance of the delivery method.  Yogurt and apparently now chocolate seem to be good delivery vehicles, however, yogurt and most probiotic pills require refrigeration; these chocolate products do not.  And neither do Nature’s Way Probifia Pearls, although they are the only pill that doesn’t (I suspect alien technology).

gimme Probiotics Dark Chocolate Candies, Youngevity Triple Treat; the list goes on and on.  Apparently, I was late to the game… (expect to see these in your local grocer soon.)

Enough shameless promotion, what about the data?

Possemiers (2010) set out to test how well probiotics survived in a robot gut simulator when mixed in chocolate.  1 billion L. helveticus CNCM I-1722 and B. longum CNCM I-3470 were mixed with either chocolate or milk.  An astounding 85% of the probiotics survived when administered in chocolate compared to only 25% with milk.  FYI the study was funded by Barry Callebaut, a fancy Belgian chocolate maker who is currently developing their own line of probiotic chocolates … it’s not a conflict of interest, it’s what companies should be doing IMO (while an independent third party would be optimal, any data are better than none).  I have no idea how well their robot gut simulator emulates actual human digestion, but these results suggest that chocolate is [at least] potentially a good candidate to deliver probiotics.

An additional benefit of loading probiotics into chocolate is that cocoa itself can function as a prebiotic.  Tzounis (2011) gave real-life live humans cocoa every day for 4 weeks and showed that bifidobacteria increased dramatically.  These findings were confirmed by Fogliano (2011), who showed (via another robotic gut simulator) that water-insoluble cocoa fractions (e.g., cocoa fiber) alone markedly stimulated the growth of bifidobacteria.

So: 1) chocolate is a good vehicle to deliver exogenous bifidobacteria; and 2) cocoa promotes the growth of endogenous bifidobacteria.  win-win.

Why is this relevant?  because probiotics by themselves don’t survive the trip!  They die off somewhere between the factory and your large intestine.  In a study by Prilassnig (2007), 7 people were fed one of 6 different commercially available probiotics for a week.  2 of the products contained bifidobacteria, Omniflora and Infloran.  None of the bifido in Omniflora survived in any of the volunteers, and the bifido in Infloran was detectable in only 1 out of 4.  Feeling lucky?

Thus, chocolate may be not only viable, but an optimal way to administer probiotics.  The bifidobacteria can feed on the cocoa while in transit (from the factory to your cupboard to your bowels), and the cocoa can directly stimulate them along with your native gut flora.

And chocolate with GOS?!  according to Davis (2010), chocolates enriched with 10 grams of GOS increased endogenous bifidobacteria a whopping 3-fold.

Formula for the healthiest chocolate on Earth? >70% cocoa, a billion bifidobacteria, and a few grams of GOS… don’t get your hopes up, however, this won’t likely be made any time soon.  Despite all of the data showing the remarkable health-promoting properties of GOS, it’s still not widely commercially available.  In the meantime, Attune’s use of inulin will have to suffice.

 

 

calories proper

 

 

 

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Posted in Advanced nutrition, fiber, gluten, microbiota, Sugar

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ORIGIN vs. pre-diabetes, Op. 83

Posted on June 24, 2012 | 1 comment

Sanofi, one of the world’s largest pharmaceutical companies, just released results from its ORIGIN trial.

Basal insulin and cardiovascular and other outcomes in dysglycemia (2012 NEJM)

The goal was to see if nightly insulin injections could prevent pre-diabetics  from becoming real diabetics.  ORIGIN was monstrous: >12000 participants, 40 countries, 6 years, etc.  FYI the subjects included in this study, mostly pre-diabetics, are not usually candidates for insulin injections (diet and lifestyle modification seem to work OK for this group).  If ORIGIN showed a positive result, then the number of patients to receive this treatment, and therefore the number of prescriptions written for Sanofi’s Insulin Glargine, would increase dramatically =  $anofi 🙂

IMHO, Sanofi is hunting for a new bunch of people to whom they can market their same old drug.  (Not a good practice.)  To stay alive in the fiercely competitive pharmaceutical industry, companies have to either invent new drugs to treat old diseases or invent new diseases that use old drugs.  In this case, they are saying that pre-diabetes, or “dysglycemia,” should be a new indication for insulin.  Pre-diabetes is not a new disease, but insulin was never warranted (Rx = diet and lifestyle modification).

I have no financial disclosures to report (but I’m open to offers).  Of moral disclosures, on the other hand, I’ve got but one.  Insulin injections are fraught with side effects and should be reserved for people who need them.  I don’t believe these people need them.

divide and conquer

After 6 long years of insulin injections (or standard care in the control group), the researchers tested for diabetes.  Lo and behold, diabetes was present in 35% of controls and 30% of the insulin-treated group; i.e., insulin-treated patients had a 20% lower chance of developing diabetes (odds ratio [OR] of 0.80, p = 0.05).  Apparently, insulin prevents diabetes.

Or not.

Exhibit A.  There’s a caveat to these diabetes rates.  The subjects were tested for diabetes at the end of the study.  Anyone who didn’t have it was re-tested a few weeks later; only those who didn’t have it were re-tested a few weeks later (during which time they received no treatment).  The researchers claim they were trying to assess the “durability of diabetes prevention.”  Here’s the rub:  25% of the patients on insulin tested positive for diabetes at the end of the study.  A few weeks later (during which time they weren’t being treated) some of the people who initially tested negative for diabetes (insulin obviously must have been protecting them), now tested positive, increasing the total to 30%.  This must have happened because they were no longer protected by insulin!  Err, no.  Diabetes in the control group, the group who was deprived of insulin from the start, went from 31% to 35% during the same exact time period.  It’s not “durability of diabetes prevention,” it’s experimental bias: by only RE-testing people who were initially negative, the total could only stay the same (if there were no false negatives) or go up (if there were false negatives).  The fact that it went up in both groups could simply mean that the re-test either: 1) detected diabetes in some people who falsely tested negative the first time around; and/or 2) generated some new false positives.  To correct for this, they should have also re-tested anyone who tested positive for diabetes.  *The importance of this difference is described below.

Exhibit B.  Disclaimer: statistics are the bane of my existence.  

The rate of disease was rather high in both groups (>>10%); if you calculated the  “relative risk (RR)” instead of “odds ratio (OR),” you’d get 0.857. An RR of 0.857 is not as pretty as an OR of 0.80 (lower is better).  Their “OR of 0.80” was barely statistically significant (p = 0.05); I’d be willing to bet that an “RR of 0.857” would not have been so lucky… so why did they choose to publish the OR?  OK, no suspense necessary:  I think if this measurement turned out non-significant, then the entire study would’ve been a waste of time and a LOT of money.  And they would have no shot at an entirely new market for their same old drug.  *This is precisely why proper diabetes diagnoses and statistical analyses were so critical in this study.  To be clear: this is going to come down to a numbers game, and the numbers don’t support a new indication for insulin in pre-diabetics.  But fuzzy math and biased testing makes this appear as though it is a debatable conclusion.

Moving on.

HbA1c, a marker of long-term glucose control was 6.4% at baseline in both groups.  Insulin therapy lowered this to 6.3% (not exactly something to write home about) while it drifted to 6.5% in controls.  This insignificant effect of insulin on HbA1c didn’t come cheap, however.  The insulin treated group experienced a huge number of severe hypoglycemic episodes:

Not surprisingly, the severity of hypoglycemia was totally downplayed in Sanofi’s press release despite it being the most robust and statistically significant finding in the entire study.

People in the insulin-treated group got a little heavier (by about 5 pounds), and surprisingly, the control group lost a little weight (about a pound).  I say “surprisingly” because this population is expected to be weight stable or gaining weight.

Lastly, fortunately, there was no difference in mortality.  This is not unexpected because the intervention was mild and the patients were relatively healthy (i.e., not people who need nightly insulin injections).  When a more intensive insulin intervention was tested on frank diabetics, the study was halted because too many people died.  Enter: The ACCORD study.

Effects of intensive glucose lowering in type 2 diabetes (circa 2008)

Intensive insulin therapy lowered HbA1c waay more in ACCORD than mild insulin therapy did in ORIGIN: 

but it also lowered lifespan: 

In conclusion:  YES, high blood glucose is the culprit, and YES, it needs to be lowered.  But NO, insulin injections are not the answer.  If you have lactose intolerance, you stop eating lactose.  These people have glucose intolerance; they need to stop eating glucose.

calories proper

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Posted in Advanced nutrition, Energy balance, insulin, Sugar

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Non-sequiter nutrition II, a sugar-thought experiment

Posted on June 20, 2012 | 1 comment

The average western diet contains about 50 grams of fructose from a variety of sources ranging from beneficial fibrous fruits to the more insidious sugar-sweetened beverages, soda and juice.  50 grams of fructose.   2 1/2 cans of Coca-Cola.

50 grams x 4 kcal/g = 200 kcal

200 kcal / 2,000 kcal = 10%

10% of your calories are provided by fructose

Even the very high end of fructose intake rarely exceeds ~85 grams, which is still < 20%.  My point?   This is nowhere near the 60% used in mouse diet studies.  Disclaimer: I think fructose causes leptin resistance because of data from such studies.  60% fructose is the fructose that causes leptin resistance and increased susceptibility to obesity.  What does this say about “normal” levels of fructose intake?  Toxic doses cause leptin resistance and obesity susceptibility in mice, well, because they’re toxic, and fructose toxicity just so happens to manifest like that (in mice).   60% is toxic.  15 cans of Coca-Cola per day (depending on who’s counting); but is it relevant?

39 grams of sugar, roughly half of which is fructose

In mouse studies, toxic doses are used for practical reasons- it’s cheap.  The animals can be rendered leptin resistant, glucose intolerant, and susceptible to obesity within a few months of feeding this expensive purified synthetic diet.  This probably (probably) takes over 100 times longer in humans simply because it’s nearly impossible for humans to ingest mouse-toxic-levels of fructose.

1. If the dose was based on body weight (like a drug; e.g., mg/kg or mpk):

60% fructose x 12 kcal/d = 7.2 kcal.  Divided by 4 kcal/g = 1.8 grams per day.

1.8 grams for a 40 g mouse = 45 g/kg.  For a 70 kg (154 lb) human = 3,150 grams of fructose or roughly 12,600 kcal.  I.e., 150 cans of soda or about a week’s worth of calories.  In other words, you’d have to eat a hypercaloric fructose-only diet for months.

2. If the dose was based on calories:

60% fructose x 2,000 kcal/d = 300 grams = 15 cans of soda or doughnuts per day.   News flash: that’s gross, but it won’t kill you.

fructose: still not as dangerous as playing in traffic

How about just lowering your lifetime sugar exposure.  39 grams of sugar is worse than 0.01 grams of stevia or sucralose.  Anyone remember “water?”  Even if you believe “a calorie is a calorie,” exclusively, it’s still really hard to burn off 39 grams of sugar.  Try running 2 miles.  Skinny kids might do this automatically after drinking a can of soda or eating a doughnut.  Not most adults.

Don’t play in traffic either.

calories proper

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Posted in Advanced nutrition, empty calories, Energy balance, Exercise, Fructose, Sugar, Uncategorized

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Decepticon Promicor (soluble corn fiber), Op. 81

Posted on June 14, 2012 | 8 comments

I heard a comedian say he wished exercise was like high school; once you get your diploma, that’s it.  You never need to do high school again.  Unfortunately, the same isn’t true with artificial nutrition.  the mad food scientists are at it again.

Enter: Soluble corn fiber (SCF), mass produced by Megatron Promitor

Over a decade ago, Atkins released low carb bars.  Well, they weren’t actually low carb per se, they were low sugar.  This was accomplished by replacing sugar with glycerol (a sugar alcohol) and polydextrose (a pseudo-fiber).  While their bars are made from cheap ingredients and low quality protein, sugar alcohols and pseudo-fibers are certainly better than sugar.

Later, sugar alcohols took off in popularity, appearing in Met-Rx Protein Plus, Detour Lean Muscle, Dymatize Elite Gourmet, etc., etc.  Glycerol was prominent in Labrada and Pure Protein bars.  Supreme Protein bars use glycerol and maltitol, and a LOT of ‘em.  Quest took a stand against glycerol and uses the lower calorie and more stomach-friendly erythritol (if it ends in “-ol,” its probably an alcohol).

More recently, the field took a considerable philosophical leap forward and starting using real fiber, good fiber.  Inulin appeared in some Atkins bars, VPX Zero Impact, and the original Quest bars.  Quest has since switched to another good fiber, isomalto-oligosaccharides.  Unfortunately no one is using GOS, yet, but they will … mark my words (that’s a prediction, or stock tip… not a threat).

But now the field has taken a turn and we have another artificial ingredient, a pseudo-fiber, with which to deal.  “Soluble corn fiber (SCF)” first appeared in Splenda Fiber packets and then in Promax LS bars.

If you’re like me, you’re asking yourself: what is this stuff?  Is it real fiber?  Is it like the super fibers inulin and GOS?  Hello Pubmed

Divide and conquer

Stewart (2010) compared SCF to 3 other fibers and maltodextrin, 12 g/d x 2 weeks =

Pullulan, a rather potent fiber, is not well-tolerated.  Resistant starch (an insoluble fiber), soluble fiber dextrin, and SCF were all OK.  The gut microbiota seemed to have no preference, as short chain fatty acid production was similar in all groups (perhaps 12 grams is subthreshold?).  Similarly, health biomarkers, hunger levels, and body weight were unaffected.

Boler (2010) compared a commercially available SCF preparation to polydextrose, 21 grams per day for 21 days in 21 healthy men (cute.)

NFC, no fiber control; PDX, polydextrose; SCF, soluble corn fiber

In this study, however, SCF didn’t do so well.  It caused gas and reflux.  Perhaps this wasn’t observed in Stewart’s study because of the lower dose (12 vs. 21 grams).  Furthermore, polydextrose reduced while SCF increased short chain fatty acid production, both of which resulting in a higher acetate:butyrate ratio.  So unlike 12 grams of any of Stewart’s fibers (including SCF), the gut microbiota seems to respond to 21 grams of SCF.  And they pooped more (both fiber groups).

Data are expressed as log cfu/g feces.

Interestingly, SCF was remarkably bifidogenic.  Much more so than PDX, MOS (see Yen et al., 2011), and inulin (see Menne et al., 2000), but WAY less than GOS (see Silk et al. 2009).

the holy grail

This same group reported a more detailed analysis of the gut microbiota which unfortunately did NOT exactly confirm their earlier finding (Hooda et al., 2012):

Data presentation is different in the two publications, and if both are true, then SCF selectively increases a few specific strains of bifidobacteria but reduces many others (enough to increase the total amount but decrease the variety).  The functional implications of this are unclear (to me).

In the meantime, SCF appears to be at most an OK pseudo-fiber substitute.  Megatron Promitor is not likely to test it against the super fibers (e.g., inulin, GOS, etc.) any time soon, so we won’t know if it’s an advance or simply a side-step.  Such is life.

 

calories proper

 

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Posted in Advanced nutrition, empty calories, fiber, Fructose, Grains, microbiota, Protein, Sugar

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XL soda ban, Op. 80

Posted on June 8, 2012 | 1 comment

People have been warned about the dangers of excess sugar consumption, but compared to the anti-smoking campaign, the recent proposal to ban XL soda’s is like bringing a cup of water to a forest fire.

In an ideal world, a proper health initiative designed to provide people (kids too) with good nutrition information would work. The new proposal takes a different route: it bans the sale of soda’s larger than 16 ounces (but you can still buy 2-12 ouncers).  I see two possible outcomes: 1) someone who would’ve bought one 24 ouncer of soda might settle for 16 ounces; 2) the one in a million customer who wanted 24 ounces will walk away with two 12 ounce sodas instead.  Win-win, right?  In the first case, the toxic sugar burden is lessened by a third.  In the second, a potentially valuable lesson on “serving size” will be on display.   Serving size 2.0, in 3-D, spelling-it-out for all to see.

It might actually work.  From a nutritional perspective, 90 grams of highly bioavailable sugar (HFCS) is a biological disaster.  Pound for pound, there aren’t many worse things you can consume… it’s the anti-thesis of “moderation.”  Regardless of your stance on the calorie debate, no one can argue that 90 grams of sugar all-at-once is more detrimental than it’s caloric content would imply.  Even for skinny people (metabolic obesity?).  It’s worse than dietary fat, and  might be THEE cause of leptin resistance.

This isn’t a TPMC original, but this graph of soda, diabetes, and obesity is just about as compelling as epidemiology can be:

 

douse those sugar cubes with artificial flavors, colors, and preservatives, and we’re good to go

If the ban goes into effect and actually impacts sales, will there be a backlash? more food company lobbying?  increased government subsidies (reduced HFCS consumption -> more taxpayer dollars used to cover the losses)?  Who knows.  If it teaches people a lesson about serving size or empty calories it might be worth it.

calories proper

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Posted in Advanced nutrition, Dietary fat, empty calories, Energy balance, Fructose, Sugar

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Resveratrol, energy balance, and another reason to distrust health journalism, Op. 79

Posted on June 2, 2012 | 2 comments


The great red wine compound “resveratrol,” at it again.  Disclaimer: 150 mg of resveratrol per day is too low and 30 days is too short to detect anything close to what was seen in the infamous resveratrol mouse study (Baur et al., 2006 Nature), which showed resveratrol to be the best drug ever on the planet.

This study, on the other hand, utilized the highest quality study design and was published in a great journal, but was a flop.   And the media got it wrong too:  “Resveratrol holds key to reducing obesity and associated risks.”  No, it doesn’t.

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans (Timmers et al., 2011 Cell Metabolism)

The study design was pristine.  Kudos.

Sample size too small (n=11) and study duration too short (30 days), but it was a randomized, double-blind, placebo-controlled, crossover study.  And although this type of drug study does not require such a thorough assessment of compliance (a pill count would’ve sufficed), the authors tested blood levels of resveratrol and its metabolites… cool.

On the docket: resVida, DSM Nutritional Products, Ltd.

Divide and conquer

The table above shows baseline characteristics in placebo and treatment groups, but this is peculiar because although the study was randomized (which is confirmed by the high degree of similarity between the two groups), it was also a crossover.

Brief review of my Prelude to a Crossover series (I  & II):

phase 1) half the subjects get drug and half gets placebo

phase 2) both groups get nothing for a washout period

phase 3) everybody switches and gets the other treatment

There are technically two baseline periods (before phase 1 and before phase 2), and all the subjects are in both.  As such, there is only one set of baseline values, so I’m not sure what the data in the above chart actually reflect.  Is this a mistake? or are these data only representative of one of the treatment sessions (which would be an egregious insult to the prestigious crossover design).

In any case, the subjects were all clinically obese, ~100 kg (220 pounds), BMI > 30, body fat > 25%, but otherwise metabolically healthy (fasting glucose levels of < 100 mg/dL).

But here’s where it starts going from technically flawed to weird:

Insulin levels may have been statistically significantly lower after resveratrol compared to placebo, but not after considering baseline insulin was ~15-16 mU in both groups.

insulin proper

The authors noted that after treatment, insulin levels were 14% lower in resveratrol compared to placebo (green circle).  BUT whatever was in that placebo pill was almost twice as good!  The placebo reduced insulin levels by 27% (red circle)!  (take THAT!)  I’m glad the authors reported these data instead of burying them, but they illustrate yet another flaw.

150 mg resveratrol (10-15 bottles of red wine) for a 220 pound person = 1.5 mg/kg; 200x less than what Baur gave his mice (300 mg/kg). Interestingly, however, this produced plasma levels of resveratrol almost 3x higher (180 vs. 65 ng/mL). I have no idea how this happened, but the benefits and lack of toxicity [at such a low dose] bode well for recreational resveratrol supplementation.

As mentioned above, resveratrol was totally safe, but how to interpret this is unclear.  Our options are: 1) good; 2) meaningless; or 3) simply not bad (which I suppose is kind-of-like #2).  It could be interpreted as meaningless because resveratrol, the anti-aging drug, is meant to be taken for a very VERY long time (i.e., forever).  This study proved that resveratrol was safe when taken for 30 days which is considerably shorter than forever.

Furthermore, the dose was phenomenally low, ~150 mg/d, so anything other than “totally safe” would be a huge red flag.

Does resveratrol in fact mimic calorie restriction, as stated in the title?  During calorie restriction, food intake declines (by definition), metabolic rate and insulin levels also decline, but free fatty acids and fat oxidation increases.  In the resveratrol group metabolic rate and insulin declined (recall however that the placebo was pretty impressive also in this regard), but free fatty acids and fat oxidation decreased.  Although proper calorie restriction trials in humans haven’t happened yet, some of these  effects don’t jive.  A decline in metabolic rate will reduce the amount of fat burned.  But relative fat oxidation also declined, leading to what could be a profound reduction in fat burning… coupled with no change in food intake (noted by the authors) this will result in increased fat mass.  Energy Balance 101- no ifs, ands, or buts.  This study was far too short-term to detect a meaningful increase in fat mass, but if these preliminary findings are true (and my interpretation of the data are correct), then this drug might just make you fat.

Oddly enough, they did detect an increase in fat accumulation in skeletal muscle:

(perhaps instead of calling it a calorie restriction-mimetic, the authors should’ve gone with exercise-mimetic, citing the athlete’s paradox (e.g., van Loon and Goodpaster, 2006)

In contrast to the popular antidiabetic drug rosiglitazone, which shifts fat storage from liver (where it causes a host of health maladies), to adipose, where it can be stored safely indefinitely, resveratrol shifted fat storage from liver to skeletal muscle.  This is interesting because while the fat storage capacity of adipose is seemingly unlimited, I doubt the same is true for skeletal muscle, which needs to do a lot of stuff, like flex.

If these findings are true, which I seriously question, then it would be interesting to see what happens to skeletal muscle fat stores after a few months, considering they doubled in only 30 days (this is unbelievable, literally).

The authors try to make the case that the increased muscle fat came from adipose, but until they report body composition data, this is a tough sell.  The elevated fasting free fatty acids support their claim, but the accompaniment of unchanged meal-induced FFA suppression with lower adipose glycerol release don’t; perhaps the missing glycerol is being re-esterified to nascent adipose-derived free fatty acids?  Increased adipose tissue glucose uptake would be supported by the lower glucose levels, but that is already more-than-accounted for by the increased RQ (indicative of increased skeletal muscle glucose oxidation).

There are some mysteries in these findings, and the improper handling of crossover data do not help.  If this paper is true and my interpretation of the energy balance data are correct, resveratrol might just make you fat :/

Unless of course you’re a mouse, in which case it’ll make you better in every quantifiable measure.

calories proper

p.s. I don’t think resveratrol will really make you fat, I think this study elucidates nothing.

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Posted in Advanced nutrition, Energy balance, Exercise, resveratrol, Uncategorized

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