Saturday, March 23, 2013

Instant Coffee, Glycemia & Caffeine Powered Post-Workout Glycogen Repletion. Fish Oil, Arachidonic Acid Release & Prostaglandin Modulation. Adipocyte Sizes & Yoyo Dieting

Judged by the way they are looking at each other they don't care about their differential glucose / insulin response too coffee, but if you do, I suggest you scroll down and read the pertaining news item.
7.3% and 21.4%, those are the SuppVersity figures of the week. Figures that stand for the 2011 youth- and 2010 adult obesity rates in Colorado and they represent the nationwide "optimum" - at least according to CDC data from the respective years. Now, it was already hard to find US states with obesity rates below the nationwide average of 13% (youths) and 27.6% (adults). What is yet even harder or rather impossible is to dig up studies which try to elucidate why Colorado is the "leanest" of the 50 US states. Non-exhausting physical activity, for example, would be a candidate, but according to Wyatt et al. the "[e]ven in Colorado, one of the leanest states, very low levels of physical activity are seen in much of the population." (Wyatt. 2005).

Wouldn't it be worth taking some time to try to elucidate what the citizens in Colorado may be doing, their fellow Americans in Mississippi (highest adult obesity rate of 34.5%) or Alabama (highest youth obesity rates of 17%) ain't doing? Are they maybe having more or less fish oil or drinking only half the amount of caffeine? I don't know, but based on today's installment of "On Short Notice", you should be able to answer whether or not it is likely that factors like these could make a difference ;-)



Coffee, Sex and Your Physique (Gavrieli. 2013) -- The latter two, i.e. sex and your physique are what determines your postprandial glucose and insulin concentrations after escalating dosages of caffeinated coffee. That's at least what Anna Gavrieli from the Harokopio University in Athens and her colleagues from overseas write in a soon-to-be-published paper.

To examine the effects of different amounts of coffee on blood glucose and insulin concentrations in the postprandial phase (after a meal) the scientist recruited thirty-three volunteers [16♀/17♂, 16 normal-weight and 17 overweight/obese, 27.3 ± 7.2 (19–44) y] who came to the lab fasted and obviously without having  had a "wake up coffee" early in the morning. When they arrived, the subjects received a standardized meal, i.e. a slice white bread, 5 g of butter and 10 g of white sugar, providing 142 kcal (6.5% of energy from proteins, 62.5% from carbohydrates and 31.0% from lipids) along with 200 mL of water or instant coffee containing either 3 or 6 mg of caffeine/kg body weight on three different occasions.
Figure 1: Usual and experimental caffeine intake in the subjects (left); effects on glucose metabolism after standardized "breakfast" (=sugar binge) + water or different dosages of instant coffee (Gavrieli. 2013)
As you can see in figure 1, the blood samples the scientists obtained before, immediately after and in regular intervals over the remaining 3 hours after the ingestion of the "breakfast" do support the hypothesis that men and women, light and heavy weights react very differently to the ingestion of 200-500mg.

So what's the verdict then? Is coffee the way to go?


Post workout caffeine supplementation?! Just like dieting, working out is one of the confounding factors which render results like the one at hand valid only in certain scenarios. Against that background it is not surprising that a 2008 study by Pedersen et al., the results of which I have plotted for you in the figure above (Pedderson. 2013), found statistically significant improvements in glycogen resynthesis w/ 8mg/kg caffeine being coingested with 4mg/kg glucose after a workout. Whether this will yield real world benefits is obviously another story ;-)
While coffee delayed the rise of insulin in response to the standardized meal and the fall of glucose concentrations from its maximum levels in the entire study sample, the glucose incremental area under the curve (IAUC) was not just different between the interventions (with both coffee amounts inducing a greater area compared to water, p = 0.009), but also varied according to the sex and body weight of the subjects:
"Secondary, subgroup analysis at the nominal level showed that this might be more evident among females (PIAUC = .05) and overweight/obese participants (PIAUC = .03). Furthermore, coffee, mainly the 6 mg dose, could be lowering insulin concentrations the first 30 min after its consumption compared to water in men and overweight/obese participants." (Gavrieli. 2013)
So what do we make of these results, now? Well, first of all, even if your breakfast does not deserve the name food, having a single regular sized cup of coffee is unlikely to to any harm. Reversing the ratio of breakfast to coffee on the other hand and having a "Sex & The City" breakfast with a croissant and a large cup of breakfast will have you run the risk of having high blood sugar afterwards (esp. if you drink that 400mg+ pot of coffee with tons of sugar).



The tissue incorporation of regular triglyceride based fish oils is inferior to their phospholipid bound brethren. Want to learn more? Check out my article on that matter from June 2012 (learn more)
3g of fish oil modulate the eicasonoid production from omega-6 fatty acids in young men (Zulyniak. 2013) -- 2g of EPA and 1g of DHA that was the dosage the 10 young healthy males (23.4 ± 1.7 years) had to consume on every day of the 3-months supplementation period in Zulyniak et al.'s experiment which was designed to "better understand the potential health benefits of fish oil supplementation in young healthy males" (Zulyniak. 2013).

What the researchers observed were the expected decreases in serum triglycerides (-38%), a significant increase in the proportion of HDL-c relative to total cholesterol, as well as - and this is the actual news - an increase in eicosanoids production, namely prostaglandin-F2α (P < 0.0001) and thromboxane-B2 (P = 0.0296), after fish oil supplementation.

The latter two are products of omega-6 metabolism and confirm the replacement of arachidonic acid (AA, the long-chain omega-6 fatty acid and the quasi-analogon to DHA) in the cell membranes of the erythrocytes by EPA and DHA. This process must have triggered the increase in PGF2α and TXB2 production of which the scientists state that
On a side note: The results of this study don't change my opinion as far as the usefulness, let alone necessity of fish oil supplementation in healthy, athletic, fish eating SuppVersity readers is concerned. I don't see any.
"[...]previous work by both Boughton-Smith et al. and Scott et al. suggest that PGE2, PGF2α, TXB2, and 6-keto-PGF1α are the primary products of the COX2 pathway when AA is in abundance. Furthermore, Scott and colleagues suggested that with chronic elevation of AA, PGF2α and TXB2 production is more likely to be up-regulated due to their vasoconstrictive qualities, which would prevent the efflux of AA and other more-damaging eicosanoids from cells into circulation." (Zulyniak. 2013)
Whether this is actually a good thing does yet appear at least somewhat questionable to me and even Zulyniak et al. have to admit that future research was necessary to confirm "the production of eicosanoids capable of regulating vasoconstriction" and thus "substantiate this hypothesis" (Zulyniak. 2013). As you can see, we are still learning new stuff about things of which every disciple of Dr Oz believes he already knew everything.



Study supports hypothesis that regression in adipocyte size during weight loss could be reason for fat loss plateaus and "walls" (Verhoef. 2013) -- As a seasoned SuppVersity veteran, you are probably aware of the possible influence the size of your fat cells could have on weight loss success, failure or stagnation (learn more).

In a previous post on the Yoyo effect, I already discussed some aspects of adipocyte morphology - including the way lower body fat tends to be more stubborn than upper body fat (read more)
A recent study from the Maastricht University does now offer further support for my previously expressed hypothesis that the reduction of adipocyte size that comes with profound weight loss in then formerly obese individuals could be at the heart of the weight loss plateaus and over-pronounced metabolic downregulation formerly obese individuals experience at way higher body fat levels than someone who has never been obese in his / her whole life. Verhoef et al. put a group of twenty-eight overweight (BMI 28-35kg/m²) healthy subjects on a very low energy diet for 2 months. The 500kcal/day period (50g carbs, 52g protein, 7g fat + multi-mineral supplement delivering the RDA of all nutrients) was followed by a 10-month period of weight maintenance.

Over the course of the low energy diet intervention period, the adipocyte size decreased by -16.7%, the body fat level, on the other hand dropped by only 4.7%. Still, the leptin levels plummeted from 20.3 to 13.1 µg/L and did not return to baseline in the course of the "weight maintenance" phase.
Figure 2: Relative changes (compared to baseline) in body composition, adipocyte volume and leptin after the dieting intervention and the miserable weight maintenance phase (Verhoef. 2013)
In how far the suppressed leptin levels were actually responsible for the fact that the "weight maintenance" phase turned out to be a very dirty, fat only bulking phase cannot be said, but we know from previous studies, that the process of shrinking in itself
"has been reported to generate cellular stress and the more [the adipocytes] shrink, the higher will be the resistance against increasing mitochondrial beta-oxidation via HADHsc [hydroxyacyl-Coenzyme A dehydrogenase] during follow-up." (Verhoef. 2013)
And as if that was not enough the slight increase in ATGL (lipolytic protein) and HADHsc in the "weight maintenance" phase are, as the scientists point out, indicative of the appearance of newly differentiated adipocytes that are are metabolically active contribute to an "improved physiological status", but could potentially make future weight loss (esp. the aesthetic one) even more difficult.

"Empty" adipocytes <> lower leptin <> more glucose-to-fat conversion <> rapid fat gain

If CLA worked in humans as it does in rodents, it could solve the "small adipocyte" problem (learn why)
Moreover, the glycolyctic and thus potentially glucose-to-fat conversion promoting enzyme Aldolase-C did not just distinguish the successful weight maintainers (low Aldolase-C) from the yoyo dieters (high Aldolase-C), it also correlated with the leptin production of the fat cells, of which we know from previous studies that it is in turn negatively correlated to their size (Skurk. 2007)... too complicated?

Ok, let's express it the other way around. The "emptier" your adipocytes are (=smaller size), the less leptin they will produce and the more likely they are to convert glucose to fat and stash that away in their empty "tummies".

Suggested read for those who want to dig further into the purported underlying effects of weight regain: Maclean PS, Bergouignan A, Cornier MA, Jackman MR. Biology's response to dieting: the impetus for weight regain. Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R581-600.



That's it for an allegedly too lengthy installment of "On Short Notice"... about as much a misnomer as the "weight maintenance" phase in the Verhoef study, I guess. Maybe some of today's Facebook news can make up for that? In the end news like
    Want to make HIIT a hit for you? Not a problem, the SuppVersity holds all the information you need. Start out with the respective two post article series and descend into the archives, where you are going to find more about HIIT, how it compares to LISS and which different regimen have shown some promise in peer-reviewed research (learn more)
  • High fat dieting reduces the beneficial effects of resistant starch - Reduction in abdominal obesity with 42% fat diet = zero (read more)
  • HIIT hits home in 8 young, untrained men - 12 HIIT sessions lead to increased V02 kinetics (read more)
  • Ice slurries are the new energy gels - Scientists observe significant increases in cycling performance (read more)
  • Physical therapy as effective as surgery for a meniscal tear and osteoarthritis - Unfortunately patients are too lazy and the revenue for the doctors too small to be used more often (read more)
  • Evolution is to blame for inflammatory disease - At least that's what the latest "paleo" research would suggest (read more)
are eventually the reason that the saturdaily short news are always so lengthy. The really short stuff is already on Facebook ;-)

References:
  • Gavrieli A, et al. Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial. Metabolism.2013 [ahead of print]
  • Pedersen DJ, Lessard SJ, Coffey VG, Churchley EG, Wootton AM, Ng T, Watt MJ, Hawley JA. High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine. J Appl Physiol. 2008 Jul;105(1):7-13.
  • Verhoef SP, Camps SG, Bouwman FG, Mariman EC, Westerterp KR. Physiological response of adipocytes to weight loss and maintenance. PLoS One. 2013;8(3):e58011.
  • Wyatt HR, Peters JC, Reed GW, Barry M, Hill JO. A Colorado statewide survey of walking and its relation to excessive weight. Med Sci Sports Exerc. 2005 May;37(5):724-30.
  • Zulyniak MA, et al. Fish oil supplementation alters circulating eicosanoid concentrations in young healthy men. Metabolism. 2013 [ahead of print]

12 comments:

  1. So...how do we completely get rid of adipocytes? I know it is difficult, but there must be a way.

    ReplyDelete
    Replies
    1. They undergo apoptosis just like every other cell, it merely takes time. Probably not the answer your looking for, but I would say get really skinny and maintain it for a while until the shrunk unused/unneeded fat cells die.

      Note: You can't completely get red of adipocytes or you would die.

      Delete
    2. Great question - I was just about to ask the same thing, thinking it might be a key phase in any diet plan.

      Of course, after a quick Google search it looks like it's more complicated than that:
      http://endo.endojournals.org/content/145/4/1849.short
      "IGF-I protects human fat cells from apoptosis by maintaining the expression of antiapoptotic proteins, Bcl-xL and Fas-associated death domain-like IL-1-converting enzyme inhibitory protein. In conclusion, we identified mechanisms of apoptosis induction in human fat cells. We furthermore demonstrate that human fat cells protect themselves from apoptosis by IGF-I in an auto-/paracrine manner."

      Considering that creatine boosts IGF-1 (http://www.ergo-log.com/creatineigf1.html), this could help explain the recent Suppversity article http://suppversity.blogspot.com/2013/03/does-creatine-blunt-fat-loss-recent.html.

      It also might imply an entirely new angle for promoting yoga and stretching: http://suppversity.blogspot.com/2012/12/exercise-round-up-hiit-prevents-angina.html

      But I'm not a physiologist... any thoughts?

      BTW, it would be great to have a Suppversity wiki for these sorts of questions....

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    3. a bit far-fetched, I believe. The best theory we have as of now is still in accordance with what Primalkid wrote: You got to keep that weight off long enough. There is an interesting 2011 paper on the issue. I already added the reference as a suggested read to the post, here is the direct link (don't worry it's a free full text) => http://ajpregu.physiology.org/cgi/pmidlookup?view=long&pmid=21677272

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    4. Thanks. That's a great and very thorough article. I've read it, and will certainly go back to it.

      Of course, it doesn't address adipocyte apoptosis, and makes it very clear that this should be an important consideration on the pathway from "post-obesity" to a normal metabolism (assuming such a thing is possible).

      I'm sure IGF-1 isn't the only signal that encourages the body to hold on to white fat cells. What are some of the others? What could cause the body to destroy or transform them? What practical impact might this have on training and diet?

      Obviously, this leads to your earlier articles on irisin and vasp, as well as the CLA article you refer to above. Care to mention a few of the many others I've probably missed? ;)

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    5. honestly, the problem I see here is that we don't really understand how / when adipocytes die a healthy cell death and what decides whether they are replaced. If I have time later today, I will think about a couple of factors, but as mentioned before: Stuff that is "healthy" e.g. fish oil, is probably exactly what keeps you fat, cause the PPAR-gamma aganoism allows fat cells to differentiate

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  2. A rise in PGF2alpha could also explain the as of yet unexplained anabolic results from omega-3 fatty acids in both young and old subjects.

    ReplyDelete
    Replies
    1. no, that is only a result of the increased insulin sensitivity - the "anabolic" PGC-alpha is the exercise induced isoform 4 => http://suppversity.blogspot.de/2012/12/the-igf-1-promoting-myostatin-reducing.html

      as of my knowledge fish oil does nothing to promote it.

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  3. Dr. Andro,

    Can you expound on the coffee data? I didn't really understand. Does having a large amount of caffeine/coffee after a meal positively or negatively influence insulin? I take about 275mg of caffeine twice per day, and some days I fall flat and other days I am running all day like an F1 car. I am trying to figure if this is related to insulin. If you could spell out the results of the study in a more informal, and basic manner, that would be much appreciated.

    Great blog. Thanks for all the information.

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    Replies
    1. I can't tell you what your personal problem is due, but I know from myself that I bunk 2h after eating after a fasted workout in the morning, whenever I use a large amount of caffeine (your dosage qualifies as large for me). Personally I believe that this is the result of postprandial hypoglycemia, which occurs due to the fact that the insulin levels remain elevated longer (that was the case in the study as well and also pumped the glycogen into the muscle) with caffeine. Now you probably don't have that much carbs in your meals and thus end up with high insulin, but no glucose => hypoglycemia

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  4. Regarding Coloradans being skinnier, you seem to have missed the obvious. Living at a higher altitude.

    Maybe they don't actually have to do anything?

    Ray Peat would say elevated carbon dioxide levels in their blood streams would keep their metabolisms higher.

    What do you think?

    ReplyDelete
    Replies
    1. true => http://suppversity.blogspot.de/2013/01/shed-11-of-your-total-fatmass-in-3.html

      but certainly not the only factor that figures here

      Delete