Science Round-Up Seconds: 8 Nootropics to Combat Stroke, Alheimer's & Co and Boost Cognitive Performance. Plus: 7 Rarely Thought of Side Effects of High Dose Glutamine.

Effects of infusion times on phenol content of black tea (Ramalho. 2012)

If you have already listened to the podcast of yesterday's Science Round-Up on the Super Human Radio Website (click here if you haven't and wan't to know what the following is all about), I suppose you will not mind that I compiled some of the complex information about "optimal" tea brewing in the illustration to the right (based on Ramalho. 2012). The colored arrows indicate the time-points at which the given compounds in the tea achieved peak values. The exact time point is also given in minutes, so that a 9' in front of the green caffeine and on the left to the green arrow pointing at the 9 min point tells you "it took 9 minutes for the caffeine content to reach it's maximum in the British tea". The graph in the background shows the catechin concentration depending on the infusion time.

Cholinergenic nootropics - What a recent review says

I guess some of you will probably have heard about piracetam or lecithine as purported enhancers of cognitive function. According to a recent review in the Journal of Experimental Pharmacology those two are yet not the most prosing agents:

Eggs are rich in choline which is an essential nutrient and was abundant in the classic BB diets (rear more)

• Piracetam: no cerebroprotective effects in patients who have open heart surgery, but does help on non-open cardiopulmonary bypass surgery (Holinski. 2008), beneficial effects in response to cerbrovascular and cognitive disorders traumatic origin (Malykh. 2010), intravenous piracetam can prevent cognitive deficits in response to anesthesia (Fesenko. 2009)

• Lecitin: does not improve cognitive deficits in patients (Amenta. 2011; Parnetti. 2007)

More promising "nootropics" - specifically in view of what most people do actually expect, when they buy such products.

• Oxiracetam: improves cognitive performance except for patients with dementia (Malykh. 2010)

• Citocoline: general neuroprotective effects (Alvares-Sabin. 2011), improvements in cognitive performance in healthy and patients and patients with dementia (Secades. 2010), helps with cognitive dysfunction in Parkinson's (Vale. 2008), helps with cognitive function in dementia of neurodegenerative and vascular origin (Parnetti. 2007), prevents cognitive decline after a stroke (Alvarez. 2011), improves recovery after stroke (Garcia-Cobos. 2010) 

• Cerebrolysine: produces signifant cognitive improvements in vascular dementia (Guekht. 2011), effective for both cognitive function and behavioral symptoms in Alzheimer's (Alvarez. 2011), promising results in patients with Alzheimer's (Plosker. 2009)

And a couple of things you would not usually associate with nootropics:

• 

  Suggested read: Amino Acids for Super Humans on the effects and differences between the various forms of carnitine (read more).

  Acetyl-L-carnitine: improves cognitive performance in patients with encephalopathy, decreases anxiety and increases general energy and wellness, as well as fatigue and age-related cognitive deficits (Malaguernera. 2008, Liu. 2008),can reduce or block neuronal death in neurodegenerative diseases (Manusco. 2007), helps ammeliorate hyperammonemia (Cagnon. 2007)

• Saffron extract: beneficial effects in mild to modest Alzheimer's  (Akhondzadeh. 2010)

• DHA (fish oil): positive effects on verbal recognition memory in old subjects (Yurko-Mauro. 2010)

Interestingly, the most profound effects appear to be brought about by acetyl-l-carnitine. In that it's worth mentioning that the benefits could still be related to cholinergic mechanisms, since it has long been known that ALCAR can increase the expression of choline acetyltransferase activity in the central nervous system (Taglialatela. 1994). And the latter is, as the name implies, necessary to form the neurotransmitter acetylcholine .

Glutamine probably not suitable for chronic high dose supplementation

Czech scientists warn about the risks of chronic high dose glutamine supplementation. I know that many of you are still too bamboozeled by the "protein for everything and let the liver take care of any glucose demands I may have" theory, of which you could probably argue that it is the bastard child of the standard BB diet with low carb. Maybe the following recently published paper by a scientist from the Charles University in Prague can help cure this "disease" (and your cognitive problems, fatigue and brainfog).

According to Holecek, the chronic ingestion of glutamine / glutamine enriched diets in can lead to...

Figure 1: In the presence of high amounts of glutamine outside of the cell, the glutamine synthesis (GLN) and with it the ammonia detoxification from muscle tissue sucks (Holecek. 2012).

"(1) Alterations in amino acid transport-as GLN shares the transporters with other amino acids, enhanced GLN intake may impair amino acid distribution among tissues and their absorption in the gut and kidneys.

(2) Alterations in GLN metabolism-GLN supplementation may impair synthesis of endogenous GLN and enhance glutamate and ammonia production.

(3) Alterations in ammonia transport-GLN supplementation may impair ammonia detoxification and negatively affect the role of GLN as the carrier of ammonia among tissues.

(4) Abnormalities in aminoacidemia-increased plasma levels of GLN, glutamate, citrulline, ornithine, arginine, and histidine and decreased levels of valine, leucine, isoleucine, glycine, threonine, serine, and proline are reported.

(5) Alterations in immune system-as GLN has immunomodulating properties, the effect of chronic GLN consumption on the immune system needs to be assessed.

(6) Effect on tumor growth-it should be elucidated whether chronic intake of GLN increases the risk of cancer.

(7) Effect of the withdrawal of GLN supplementation-due to the adaptive response of the organism to enhanced GLN consumption, the withdrawal of GLN may enhance the risk of health problems resulting from GLN deficiency." (Holecek. 2012)

Remember the post on the ammonia induced peripheral and central fatigue with high dose chronic BCAAs supplementation?

In view of the fact that some people consumer up to 40g of glutamine regularly, Holecek demands that "long-term studies should be performed" to test the side effects and evaluate whether there is any benefit at all to justify chronic consumption of a GLN-enriched diet.

So, relying on glutamine instead of carbs, as smart as this idea appears to be in the current carbophobia, could actually make you stupid due to the disruption of the intracellular ammonia detoxification, which is not a problem in muscle only, but also in the brain.

In the end, what we are seeing here is just another instance of a disruption in the natural balance of things. Ornithine, citrulline and arginine, for example are involved in the detoxification of ammonia via the urea cycle. They are however not the only bottleneck to the system.

Obviously your liver and kidneys will have to handle the clearance. People with liver problems (or persons taking "supplements" or NSAIDs that may impair the liver function) are therefore particularly prone to hyperammonemic encephalopathy (Kanamori. 1996; Lemberg. 2009)

Bottom line: Glutamine, just like everything else, in moderation and by no means so much that your body runs on glutamine as fuel. Aside from the mentioned amino acids that help the clearance of ammonia from the blood stream, taurine appears to exert a direct protective affect in the brain (Chepkova. 2006), and lactulose (a fermentable carbohydrate) can reduce the ammonia influx from ammonia producing bacteria in the gut (Vince. 1980). So if you want to wear a helmet when you bang your head against the wall, these would be suggested "take supplement B in order to counter the side effects of supplement A" - side effects of a supplement you would not even have to take, by the way (100% bro-logic ;-)

References: 

• Amenta F, Carotenuto A, Fasanaro G, Lanari A, Rea R, Traini E. Preliminary results of Ascomalva trial on the association of donepezil and choline alphoscerate in Alzheimer’s disease with associated cere-brovascular injury. G Gerontol. 2011;59:89–9.
• Akhondzadeh S, Shaf iee Sabet M, Harirchian MH, Togha M. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativusin the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology (Berl). 2010;207:637–643.
• Alvarez XA, Cacabelos R, Sampedro C, et al. Efficacy and safety of cerebrolysin in moderate to moderately severe Alzheimer’s disease: results of a randomized, double-blind, controlled trial investigating three dosages of cerebrolysin. Eur J Neurol. 2011;18: 59–68.
• Alvarez-Sabín J, Román GC. Citicoline in vascular cognitive impair-ment and vascular dementia after stroke. Stroke. 2011;42(Suppl 1): S40–S43.
• Cagnon L, Braissant O. Hyperammonemia-induced toxicity for the devel-oping central nervous system. Brain Res Rev. 2007;56:183–197.
• Chepkova AN, Sergeeva OA, Haas HL. Taurine rescues hippocampal long-term potentiation from ammonia-induced impairment. Neurobiol Dis. 2006 Sep;23(3):512-21.
• Fesenko UA. Piracetam improves children’s memory after general anaesthesia. Anestezjol Intens Ter. 2009;41:16–21. Polish
• García-Cobos R, Frank-García A, Gutiérrez-Fernández M, Díez-Tejedor E. Citicoline, use in cognitive decline: vascular and degenerative. J Neurol Sci. 2010;299:188–192.
• Guekht AB, Moessler H, Novak PH, Gusev EI; Cerebrolysin Investigators. Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial. J Stroke Cerebrovasc Dis. 2011;20:310–318. 
• Holecek M. Side Effects of Long-term Glutamine Supplementation. JPEN J Parenter Enteral Nutr. 2012 Sep 18.
• Holinski S, Claus B, Alaaraj N, et al. Cerebroprotective effect of piracetam in patients undergoing coronary bypass surgery. Med Sci Monit. 2008;14:153–15.
• Kanamori K, Ross BD, Chung JC, Kuo EL. Severity of hyperammonemic encephalopathy correlates with brain ammonia level and saturation of glutamine synthetase in vivo. J Neurochem. 1996 Oct;67(4):1584-94.
• Lemberg A, Fernández MA. Hepatic encephalopathy, ammonia, glutamate, glutamine and oxidative stress. Ann Hepatol. 2009 Apr-Jun;8(2):95-102.
• Liu J. The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview. Neurochem Res. 2008;33:194–203.
• Mancuso C, Bates TE, Butterfield DA, et al. Natural antioxidants in Alzheimer’s disease. Expert Opin Investig Drugs. 2007;16:1921–1931.
• Malaguarnera M, Gargante MP, Cristaldi E, et al. Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Arch Gerontol Geriatr. 2008;46:181–19
• Malaguarnera M, Gargante MP, Cristaldi E, et al. Acetyl-L-carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci. 2008;53: 3018–3025
• Malykh AG, Sadaie MR. Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. Drugs. 2010;70:287–31
• Pantoni L. Treatment of vascular dementia: evidence from trials with non-cholinergic drugs. J Neurol Sci. 2004;226:67–70
• Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F.  Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation? J Neurol Sci. 2007;257:264–269.
• Ramalho SA, Nigam N, Oliveira GB, Alves de Oliveira P, Matos Silva TO, Passos dos Santos AG, Narain N. Effect of infusion time on phenolic compounds and caffeine content in black tea  Food Research International; 13 December 2012 [ahead of print]
• Secades JJ. Citicoline: pharmacological and clinical review. Rev Neurol. 2010;52 Suppl 2:S1–S62.
• Vale S. Current management of the cognitive dysfunction in Parkinson’s disease: how far have we come? Exp Biol Med (Maywood). 2008;233:941–951.
• Vince AJ, Burridge SM. Ammonia production by intestinal bacteria: the effects of lactose, lactulose and glucose. J Med Microbiol. 1980 May;13(2):177-91.
• Yurko-Mauro K. Cognitive and cardiovascular benefits of docosahexaenoic acid in aging and cognitive decline. Curr Alzheimer Res. 2010;7:190–196.

Post-Workout Chlorogenic Acid / Caffeine Supplementation - For Good or For Worse? Plus: Glycogen Synthesis & Why A Post-Workout May Be a Better Idea Than You'd Think

"Done,... where is my post-workout coffee?" - Post workout caffeine / chlorogenic acid - good or bad idea?

I know it's kind of late to post an article like this months after the ISSN conference, but I recently hit on an overview of the poster presentations and noticed that I did actually miss a couple of interesting studies. Don't worry, I won't be addressing a couple of them in the weeks to come in some detail.

Not all are really news-worthy, but aside from today's item on caffeine and chlorogenic acid, there were also posters on nutrient timing, different forms of protein, commercially available supplements and other stuff that's all classic "SuppVersity fodder"?

Chlorogenic acid? Isn't that Ozzy's green coffee bean stuff? You are correct, but could actually read about it here at the SuppVersityway before it was on Dr. Oz. Plus, I still believe that there is something wrong with the corresponding study and do still have to meet someone who has successfully lost weight by just adding some GCB to the diet, which is effectively what Ozzy and the study promised | learn more

Caffeine and chlorogenic acid? Right, that sounds like green coffee bean extract, but in the case of Jason R Beam et al.'s study, we are dealing with an artificial stack of

• 5mg/kg body weight of caffeine plus 75 g of dextrose (CAF), 
• 5 mg/kg body weight of chlorogenic acid plus 75 g of dextrose (CGA), or 
• 5 mg/body weight of dextrose plus 75 g dextrose (PLA)

the 10 moderately to highly trained study participants consumed after 30-minutes of  high intensity cycling at 60% of peak power output (~90% HR max).

Figure 1:

As you can see in Figure 1, we do see quite extra-ordinary effects of the administration of both caffeine and chlorogenic acid on post-workout glucose metabolism. The changes in the area under the cure (2h AUC) do yet overestimate the real-world difference between the glucose curves (not shown), which have a slightly higher spike immediately after the ingestion.

"Ok, no caffeine after a workout - right!?"

In the case of caffeine that was to be expected, it has after all been shown to decrease the insulin-induced glucose uptake (Graham. 2001). The fact that the glycemic response was - within the statistically probable margins - still identical, is simply the result that the stimulation of glucose uptake and hepatic, as well as muscular glucose storage is not really necessary as long at the glycogen stores are low. Accordingly, a 2004 study by Battram et al. was unable to show any effect of caffeine ingestion on proglycogen and macroglycogen resynthesis after a workout (Battram. 2004).

Figure 2: Skeletal muscle glycogen content (mmol/kg dw) immediately after exercise 0. 1, 4h after cycling to volitional fatigue (70% Vo2Peak) w/ or w/out coingestion of 8mg/kg BW (+ 1g/kg glucose) after the workout - left; corresponding levels of pCAMK and p-Akt (arbitrary units) 1h and 4h after the workout, right (Pederson. 2009).

As you can see in Figure 2 the net amount of glucose that ends up in the musculature after exhaustive (if you don't deplete the stores this effect won't be there) exercise was in fact favorably affected by the congestion of 8mg/kg caffeine and 1g/kg glucose in with caffeine in the 7 endurance-trained cyclists and triathletes in a study by Pedersen et al. from 2009. The exact underlying mechanisms of this beneficial effects, as well as dose response relationships do yet still have to be determined, but Pederson et al. speculate that it may a result of the increased activation of p-AKT:

You think you've heard about p-Akt before, but are not sure where? Well, chances are it was here at the SuppVersity, yet probably in a different context, i.e. as part of the Intermittent Thoughts on Building Muscle | read more

"The increase [in p-AKT] tended to be higher after the ingestion of caffeine with CHO after both 1 and4hof recovery, but failed to reach statistical significance. Akt seems to regulate glucose uptake by phosphorylating and inhibiting the Rab-GTPase-activating protein AS160. Thus it is tempting to speculate on the role of Akt in glucose transport given that the Akt substrate AS160 has been identified as an important regulator of GLUT4 traffic.

We have recently shown that AS160 is phosphorylated in human skeletal muscle after endurance exercise with concomitant phosphorylation of Akt (7), providing correlative evidence to suggest AS160 is an exercise-responsive protein with a role in glucose uptake." (Pederson. 2009)

If we discard potential negative effects of the caffeine-induced CNS activation on post-exercise nervous system recovery, and take into account that the elevated glucose + insulin AUC Beam observed in the experiments for his dissertation and ISSN conference poster are negligible, the preliminary bottom line for post-workout caffeine intake would be: "If glycogen resynthesis is what you are looking for, do it!"

"What about the effects of chlorogenic acid. Shouldn't the exact opposite happen?"

Now that we've searched for explanations of the effects of caffeine on post-workout glycemia we are still left with the astonishing increase in the two-hour glucose area under the curve, i.e. total glycemia, Beam observed in the glucose + chlorogenic arm of his study.

Figure 3: Insulin (AUC) for each subject during the placebo, caffeine, and chlorogenic acid trials (Beam. 2013)

If you take a closer look at the data to the right, you won't get a mechanistic explanation of the underyling reasons, but you will at least get an idea of what statistical significance means and why we are talking about it in almost every study analysis, even if it does not equate physiological significance.

In this particular case the 2 outliers, subject 1 and subject 6 do not simply "ruin" the statistical significance, they are actually the (almost) only reason that insulin response is not virtually identical to the placebo trial.

As far as potential negative consequences of the post-workout consumption of cholorgenic acid goes, you do thus not have to be worried, whether it is actually a good idea to use a supplement that's meant to increase the activity of AMPK in a phase, when the latter is already maximized, is however questionable. In the best case, the additional benefits will be minimal, in the worst case it  CGA will ruin the glucose repartitioning effects of the workout by increasing AMPK and thus glucose uptake in the fat cells (Alonso-Castro. 2008).

If you actually have problems with insulin resistance / glucose uptake (which is not the case for 90%+ of the people who buy corresponding supps), I suggest you check out this list of useful anti-diabetes agents.

Bottom line: I would assume that you will not have expected that, but based on the results of the study at hand and the review of previous literature the effects of caffeine and chlorogenic acid on post-workout glycemia are most likely negligible.

If you still insist on supplementing with one or the other immediately after a workout, though, there would be a rationale to use caffeine. The use of chlorogenic acid, green coffee bean extracts or any other highly advertised and for physical culturist 100% useless "nutrient repartitioning agents", would be at least non-sensical, in view of the potential negative effect on the true nutrient repartitioning effects, even potentially downright counterproductive.

References:

• Alonso-Castro, A. J., Miranda-Torres, A. C., González-Chávez, M. M., & Salazar-Olivo, L. A. (2008). Cecropia obtusifolia Bertol and its active compound, chlorogenic acid, stimulate 2-NBD glucose uptake in both insulin-sensitive and insulin-resistant 3T3 adipocytes. Journal of ethnopharmacology, 120(3), 458-464. 
• Beam, J. (2013). The effect of post-exercise caffeine and chlorogenic acid supplementation on blood glucose disposal and insulin sensitivity.
• Battram, D. S., Shearer, J., Robinson, D., & Graham, T. E. (2004). Caffeine ingestion does not impede the resynthesis of proglycogen and macroglycogen after prolonged exercise and carbohydrate supplementation in humans. Journal of Applied Physiology, 96(3), 943-950.
• Pedersen, D. J., Lessard, S. J., Coffey, V. G., Churchley, E. G., Wootton, A. M., Ng, T., ... & Hawley, J. A. (2008). High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine. Journal of Applied Physiology, 105(1), 7-13.

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.

Double Your Workout Volume With 3,4-DA - Chlorogenic Acid Metabolite, Dihydroxycinnamic Acid, Makes Rats Run 60% Longer, 30% Faster 90% Further!

Image 1 (sodahead.com): Another reason to supersize your cup of coffee; no not the girl, or ... well ;-)

Those of you who can no longer be without their well-deserved daily dose of SuppVersity news will probably remember the amazing weight loss effects an extract from green coffee beans yielded in a 2012 trial by Vinson et al. (cf. "GCB Another Fatloss Acronym: Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 weeks"; Vinson. 2012) and while I am still not convinced that you would see similar results in non-obese individuals, another recently published study by Novaes et al. does suggest that even those of you who don't think that they have another lbs of body fat to spare, could largely benefit not just from the caffeine, but also from the 0.5-1.0g of chlorogenic acid and the subsequent conversion of the latter into 250-500mg of 3,4-Dihydroxycinnamic acid (3,4-DA) even 400ml of regular coffee do contain (Chung. 2004; Novaes. 2012).

3,4-DA is like legal gear from the brown brew

Compared to placebo and vitamin C (25mg/kg), the hydrolyzed chlorogenic acid molecule, of which the 8-week-old male Wistar rats in the Noves study received either 5mg or 25mg per kg body weight (HED for 80kg human being: 65mg or 324mg) had almost incredibly potent "ergogenic" effects:

Figure 1: Time to fatigue (TTF), speed, workload and total distance covered (secondary axis) during exhaustive treadmill running after oral supplementation with placebo (control), vitamin C or 4,5 DA at doses of 5mg/kg and 25m/kg (based on Novaes. 2012)

As you can see in figure 1 the rodents in the high dose group ran 60% longer, 30% faster, 90% further and performed overall twice as much work (42 vs. 21 kg*m) than the rodents who had received the human equivalent of ~325mg vitamin C before a forced running test on a motor-driven treadmill.

Less ROS = Increased efficacy?!

Interestingly, the lactate levels of the 3,4-DA rodents were significantly lower and the remaining liver glycogen levels were significantly higher than in the placebo and vitamin C group (see figure 2).

Figure 2: Serum triglyceride (group effects non-significant) and lactate levels, hepatic glycogen content and protein arbonyl and malondialdehyde levels after the exercise (based on Novaes. 2012)

As Novaes et al. point out this suggests that the effect is partly mediated by a higher metabolic efficiency. The latter is probably a direct result of the profound reduction in reactive oxygen specimen, which have been associated with impairments of the cellular metabolism and subsequently reduced aerobic energy production (Atalay. 2002) - a hypothesis that would be supported by the reduced levels of protein carbonyl and malondialdehyde in the liver of the 3,4-DA treated rodents.

But don't we need ROS?

Image 2: Don't worry those love handles will go away - rather with the antioxidant + caffeine power of coffee than without it!

These observations are also quite revealing as the offer an alternative explanation for the previously mentioned possibly negative effects of antioxidants on the exercise-induced improvements in glucose metabolism (cf. "Update on Antioxidants & Exercise - Neither Vitamin C Nor E Have ANY Effect on the Response to Intense Exercise"): If high doses of other anti-oxidants have the same beneficial effects on metabolic efficacy, it stands to reason that even weaker antioxidants than 3,4-DA would spare liver (and muscle) glycogen and thus reduce the exercise-induced expression of AMPK of which you may remember from posts like "AMPK II/III: Leucine, HMB and a Glimpse on Other AMPK Modulators" that it is expressed in response to intracellular glucose, or more specifically ATP depletion, and the subsequent increase in glucose (re-uptake).

A huge cup of coffee before your workout will therefore neither hamper the weight loss, nor the health effects of your workout, as long as you do actually make use of its ergogenic effect and train 60% longer, 30% faster, 90% further and perform overall twice as much work... just kiddin', if you train regularly you should be more concerned about keeping the amount of inflammation at bay - some is probably necessary, too much counter-productive, but that would the topic of another SuppVersity post. I for one am now going to get myself a nice cup of coffee...yummy!

Suggested reads on coffee:

• GCB Another Fatloss Acronym: Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 weeks.
• Warding Off Holiday Weight Gain 2.0: The Anti-Diabesity Effect of Coffee Goes Beyond its Caffeine Content.
• Only "Real", Not Decaffeinated Instant Coffee Increases Fatty Acid Oxidation. Revisited: Caffeine's Dose-Dependent Effects on Testosterone & Cortisol Response to Exercise
• Study Identifies Caffeic Acid Induced AMPK-α2 Activity Behind the Fat Burning, Insulin-Sensitizing & Life-Extending Effects of Coffee. Plus: Why Creatine & Coffee Don't Mix!

• all about coffee

References:

1. Atalay M, Laaksonen DE. Diabetes, oxidative stress and training. Journal of Sports Science and Medicine 2002 Jan; 1 - 14.
2. Chung TW, Moon SK, Chang YC, Ko JH, Lee YC, Cho G, Kim SH, Kim JG, Kim CH. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J. 2004 Nov;18(14):1670-81.
3. Novaes RD, Gonçalves RV, Peluzio Mdo C, Natali AJ, Maldonado IR. 3,4-dihydroxycinnamic Acid attenuates the fatigue and improves exercise tolerance in rats. Biosci Biotechnol Biochem. 2012 May 23;76(5):1025-7.
4. 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. Epub 2012 Jan 18.

GCB Another Fatloss Acronym: Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 weeks

Image 1: Coffee! Would you have recognized it?

HCG, GTE, GSE, DNP and obviously ECA! If you have ever done some research into pharmacological and non-pharmacological weight loss agents, you are probably familiar with this alphabet soup. But would you know right off your head what GCB stands for? No, ...? "G" as in "green", "C"  as in "coffee" and "B" as in "bean" - if you make it GCBE, with an "E" for "extract" it could make another item on your list of potential weight loss tools - moreover, one that has actual human data to back it up.

Green seems to be a good color for weight loss ;-)

In a recently published paper, a group of scientists from the University of Scranton, in the US, and the Health Sciences Clinic in Bangalore, India, report on the results of 22-week cross-over trial, in which the researchers tested the efficacy and safety of high (3x 350mg) and low (2x 350mg) doses of a commercial green coffee extract product (GCA by Applied Food Sciences; a 45.9% chlorogenic acid in an extract from unroasted = green coffee beans) in 16 overweight subjects (eight males and eight females; aged 22–46, mean age 33.19y; BMI 28.22km/m²). In each of the three arms of the studies, the subjects received the high and low dose supplement in a different order, so that the individual supplementation protocols looked like this:

• group 1: 6 weeks 3x 350mg / WA / 6 weeks 2x350mg / WA / 6 weeks placebo
• group 2: 6 weeks 2x350mg / WA / 6 weeks placebo / WA / 6 weeks 3x 350mg
• group 3: 6 weeks placebo / WA / 6 weeks 3x350mg / 6 weeks 2x 250mg
  * WA: 2-week wash-out period without supplementation

The results you see in figure 1, especially in the beginning of the study, are impressive, given the fact that the reduction in calorie intake (which is unfortunately not group-speficic) amounted to no more than -2% over the whole study period.

Figure 1: Mean weight over the whole 22-week study period and change in body fat percentage during the individual 6-week supplementation phases (data calculated based on Vinson. 2012).

It is yet somewhat suspicious that a) this phenomenon arose in both the high and the low-dose group (it was even more pronounced in the latter) and b) that the group which received the high dose in the beginning of the study experienced a profound "jojo-effect", when during the last 6-weeks, in which they received the placebo supplement.

Maybe helpful for the obese, but questionable for anyone who is already lean

Image 2: Coffee beans are not the only food (or raw material for a beverage) that loses some of its active and oftentimes healthy ingredients, when it is heated, or, as with coffee beans, roasted.

Moreover, the actual fat loss, which was measure only via one of those notoriously unreliable body impedance devices (SFB7 from Impedimed) is not exactly impressive and was statistically significant not only in the high and low dose, but also in the placebo phases of the trial (the 0.3% difference is laughable) left the subjects with still more than 23% body fat on their hips. So that, despite the existing evidence for the health and fat loss benefits of chlorogenic acid, I personally have my doubts that anyone with a dialed in nutrition and exercise regimen, would derive great fat-loss benefits from supplementing with two or three servings of this extract per day.

If you are yet still relatively chubby (the Peter Griffin type from the "Intermittent Thoughts") just interested in losing weight (an average of 16lbs or -10.5% in the study at hand) - and for the pre-obese individuals in the study at hand, this could actually be the case - GCB may really be an acronym to memorize, though.

Note: I stuck to the acronym GCB, also because it differs from the brand name of the patented "GCA" used in the study. After all, there is no reason to pay for the "A", when all you have to look for is a green coffee bean extract with a cholorogenic acid content of ~46% and a total chydroxycinnamic acid of ~57% (note: chlorogenic acid is in fact one of those chydroxycinnamic acids). And if you are not into popping pills, why don't you just make your own green coffee bean instant coffee - should work just as it is described in this guide on eHow for the regular, roasted variety... ah, and if you do, let me know how it tastes ;-)

Study Identifies Caffeic Acid Induced AMPK-α2 Activity Behind the Fat Burning, Insulin-Sensitizing & Life-Extending Effects of Coffee. Plus: Why Creatine & Coffee Don't Mix!

Image 1: I've got news for you: Real coffee does not come in brown sterophome cups ;-)

Ever since Starbucks came out with the "McDonald's version" of what used to be the drink of the popes and kings, coffee has gotten sort of a bad reputation. It is supposed to "burn out your adrenal glands" (I bet most people who support this hypothesis don't even know where the adrenal glands are situated), derive you of  vital nutrients and water, reduce insulin sensitivity, give you palpitations and high blood pressure, ... I guess, you know the whole litany. If we take a closer look at the contemporary scientific consensus, many of these arguments against your 2-3 cups of coffee per day lack any scientifically verified basis. Others apply only if you (ab-)use the uber-potent high-caffeine, high sugar, low polyphenol Starbucks brew as "rocket fuel" on your mission not to mars, but to your first (or next?) heart attack.

Live longer, live leaner and live diabetes-free with...coffee!

I guess, some of you will probably remember my pre-Christmas blogpost on the "Anti-Diabesity Effects of Coffee", in which I elaborated on the results of a recently published paper by Matsuda et al. who observed significant reductions in weight gain in rodents receiving either diluted coffee or pure caffeine in addition to a fattening high fat (+high carb) diet. Contrary to the body weight gain, which was ameliorated about equally effective by both treatments, the "whole coffee" treatment had a much more pronounced effect on the particularly unhealthy visceral fat in the epididymal area (cf. previous news, figure 2).

Figure 1: Molecular structure of chlorogenic and caffeic acid, two of the major phenolic compounds in coffee beans (adapted from Tsuda. 2012)

Although these results clearly indicate that there is more to coffee than the world's most popular recreational drug, caffeine, they cannot answer the question what exactly this "more" would be. The most likely candidates obviously are the two major plant phenols in coffee beans, caffeic acid and its ester, cholorogenic acid (cf. figure 1). Both, caffeic, as well as cholorogenic acid have already been studied for their antihyperglycemic (=blood glucose lowering) effects in animal models (e.g. Rodriguez de Sotillo. 2002; Bassoli 2008), but the molecular mechanism by which they perform their blood sugar reducing magic had not been fully elucidated until Satoshi Tsuda and his colleagues from the Laboratory of Sports and Exercise Medicine at the Graduate School of Human and Environmental Studies of the University of Kyoto in Japan conducted an experiment which identified the AMPK-pathway about which you have already learned so much, here at the SuppVersity, as one, if not the underlying cause of the beneficial health effects of coffee.

In view of the fact that cacao, just like coffee contains both chlorogenic and caffeic acid (Duke. 2000), it is almost certain that the health benefits which have been ascribed to the consumption of phenol rich dark chocolate within the last couple of years can be traced back to increases in skeletal muscle AMPK-phosphorylation, as well.

To prove their hypothesis that caffeic acid and / or chlorogenic acid act directly on the AMPK-pathway in skeletal muscle,  the scientists incubated isolated rat epitrochlearis muscles with different amounts of the coffee phenols and measured the phosphorylation of AMPKα Thr¹⁷² and ACC Ser⁷⁹

Figure 2: Relative AMPK-phosphorylation in isolated rat epitrochlearis muscles in response to incubation with 0.01, 0.1 and 1mM of chologenic and caffeic acid (left); relative increase in AMPK-phosophorylation after incubation with 1mM of caffeic acid for 5, 15, 30 and 60 min (right; data adapted from Tsuda. 2012)

As you can see, caffeic acid, but not chlorogenic acid lead to dose- and time-dependent increase in skeletal muscle AMPK-phosphorylation (cf. figure 2). A similar response was observedfor its downstream target (data not shown in figure 2), Acetyl-CoA carboxylase (ACC), an enzyme that is directly involved in the regulation of mitochondrial fatty acid oxidation.

Figure 3: Relative increase in AMPK isoform phosophorylation (left) and increase in glucose transport measured with 3O-methyl-glucose as a marker (right) in skeletal muscle of rats after incubation with 1mM of caffeic acid for 30 min ( data adapted from Tsuda. 2012)

And while it does not come as a surprise that the increase in AMPK went hand in hand with the previously observed increase in glucose uptake the underlying mechanisms of which the scientists tried to uncover (cf. figure 3), it is of particular importance for physical culturists and anybody else who is interested to burn fat, while maintaining / building muscle that this effect was mediated by the alpha 2, not the alpha 1 isoform of AMPK. As I hope those of you who have been following my dissertations on AMPK in the Intermittent Thought (Part 1, Part 2, Part 3) will be aware of, the former, i.e. AMPK-alpha-2 is also expressed in response to exercise and does not reduce muscle protein synthesis by compromising the mTOR response (note: due to the isoform-specificity of caffeic could be called a true exercise mimetic).

Figure 4: Relative amounts of ATP and phosphocreatine (PCr) and phosphorylated AKT in skeletal muscle after incubation with 1mM of caffeic acid for 30 min (data adapted from Tsuda. 2012)

That you do not have to be afraid of losing muscle, if you ramp up your skeletal muscle AMPK expression by caffeic acid, is also supported by the absence of any detrimental effects on skeletal muscle protein kinase B (AKT) expression and the adenosin-triphosphate (ATP) levels in the skeletal muscle samples (cf. figure 4). What is intriguing, though, is the statistically significant decrease in the amount of phosphocreatine, a phosphorylated creatine molecule your muscle (and brain) tissue uses as a rapidly mobilizable energy reserve.

Caffeic acid won't decrease protein synthesis, but could reduce the effectiveness of creatine

And while Tsuda et al. mention the detrimental effect caffeic acid exerts on intra-muscular phosphocreatine stores in the discussion of the results, they are not able fully explain this observation which reminds me of the old "myth" that the caffeine in coffee would compromise the beneficial effects of creatine supplementation... I guess we have just found why some studies did in fact support this hypothesis. If the caffeic acid induced increase in AMPK-phosphorylation goes hand in hand with a reduction in the amount of stored creatine phosphate (PCr), this could mean that you would need more creatine to achieve and maintain "maximal" levels of this high-performance energy reserve.

As you can see, it is always the same, with every question we answer a new one arises. What did Socrates say? Yeah: "I know that I know nothing!" I suppose this is a good concluding word for today's blogpost. Come back tomorrow if you want to know what else you do not know ;-)

Red Meat and Cancer? Not if You Protect Yourself With Coffee. A Cup of Coffee With / After Meals Will Do the Trick

Coffee-Chile-Cocoa Rubbed Sirloin, Creamed Kale (recipe) - The perfect way to eat your red meats?

I just realized that the last SuppvVersity article on coffee is about three months old. In view of the myriad of health benefits that have and (I guarantee) will still be associated with habitual coffee consumption (examples: heart disease - Lopez-Garcia. 2006; diabetes - van Dam. 2005; cancer - Wilson. 2011). This is obviously something that has to be changed. Luckily, there are scientists like Roman Sirota and his colleagues from the Hebrew University of Jerusalem who keep the interesting papers coming. For the Israeli scientists, the beneficial effects the consumption of coffee - roasted-ground coffee, to be precise - appears to have on the influx of maldonialdehyde (MDA) from the gut was at the center of their latest experiments.

Real coffee, real benefits - Filter coffee, but not instant will do the trick

While this is not directly related to the MDA issue, it is still intriguing that past studies on the role of coffee consumption in the etiology of gastric cancer are highly inconclusive. While studies conducted in the US and Europe have shown hardly relevant increases (US) and decreases (EU) in gastric cancer risk with high vs. low coffee intake, data from South America suggests that coffee consumption reduces the incidence of gastric cancer by 46% (Botelho. 2006). Without understanding the underlying effects the consumption of coffee has on both, the gastrointestinal tract and the stuff that comes into our system via that route, it is however difficult to come up with potential explanations for this discrepancy; and this is where the observations Sirota et al. made could actually come handy.

Figure 1: A coffee made from ground Turkish coffee or green coffee bean powder enriched (2%) ground coffee with (and most likely also after) a red meat meal reduces the AUC of the serum MDA levels (nmol/L*min) in the postprandial phase by ~30% (* indicates p < 0.05; data based on Sirota. 2013)

As you can see in figure 1, the co-ingestion of coffee with a standardized  red-meat cutlet meal significantly the absorption of MDA and subsequent changes in plasma MDA concentration in the ten volunteers who participated in this randomized cross-over trial (all volunteers participated in all conditions).

While green bean enriched coffee is slightly more potent, regular ground coffee does suffice

Green coffee beans suppements which contain up to 80% polyphenols of which∼50% are CGAs can be used as an alternative to coffee from ground roasted bean and may also help you burn body fat (read more)

With MDA being the most abundant active carbonyl generated in foods from lipid peroxidation in vitro, and a concentration of up to 300 mol/kg in red meat, food borne malondialdehyde appears to pla an important role not only locally, but also systemically. And this can have far reaching health effects, since the surge of plasma MDA levels following a red-meat meal has the potential to oxidize the low density lipoproteins (LDL; Kanner. 2012). With oxidize LD being one of the main initiators of atherogenesis and in view of the fact that the removal of circulating modified-LDL (=oxidized LDL) particles from the blood  has been shown to prevent the development of atherosclerosis without having to resort to statin therapy and irrespective of the total amount of LDL (Ishigaki. 2008), the importance Sirota et al.'s results can hardly be overestimated.

And while it is important to note that green coffee bean powders and extracts could be an alternative (see image on the right) for all of you who are not into drinking coffee, the instant and most probably even the standard "pad coffees" are no suitable alternative to the ground coffee beans used in this study, because their MDA inhibitory effect on muscle food lipid peroxidation is 2-5x lower than that of a cup of coffee from ground roasted beans.

Did you know that Coffee is also a testosterone booster? In this case it does yet appear as if the major player is caffeine, which probably does not play a role as far as the anti-MDA effects in the study at hand are concerned (learn more).

How does the protective effect work and is it red meat specific? The anti-oxidants blunt the pro-oxidative iron-redox cycle catalysis. Obviously this does happen in the gut first, but the beneficial effects don't stop at the wall of your intestines. The combination of lower MDA influx and increased circulating antioxidants will have systemic effects and could also help blunt the exercise induced increases in malondialdehyde (specifically in the presence of high amounts of highly oxidizable omega-3s, cf. "Increased Lipid Oxidation in Athletes With Omega-3 PUFAs"). What's more, the beneficial effects on lipid peroxidation appear for once to be independent of the caffeine content of coffee... the word "appear" does yet indicate that this hypothesis of mine and the efficacy of decaf. would still have to be experimental verified.

As Sirota et al. hypothesize, this is probably due to the extraction process that's used to produce instant, coffee. The latter extracts "only the hydrophilic, more soluble, and small polyphenols molecules" and leaves the more efficient hydrophobic polyphenols in the "waste" that's generated during this process. Similar but less pronounced differences will obviously be observed when you compare different brands of  roasted coffee or - as the producer of the enriched coffee brand used in the study did it - simply add a couple of mg of coffee bean extract.

So thumbs up for the post-meat-meal-coffee, right?

Table 1: Coffee doesn't only have the highest polyphenol content on a per serving base (compared to other "high potentials" as black tea, green tea, cacao and even berries and cherries), the polyphenols also make it into the lumen, where they work (among other things) their anti-MDA effects (Williamson. 2012).

As the researchers, whose study was supported by a grand from the Israeli National Science Foundation and who declare no conflict of interest point out, their

"[...] results seem to be of great importance for further investigations on the involvement of dietary polyphenols and other antioxidants in human health." (Sirota. 2013)

Moreover, their study appears to support their hypothesis that "coffee, the most popular beverage in the world, supplies the most significant portion of daily in-take of dietary antioxidants" (Sirota. 2013) - a contribution that's significant enough to "effectively control lipid peroxidation in the stomach medium and thus prevent post-prandial absorption and plasma MDA modification" (Sirota. 2013).

And the researchers even have a very concrete advice for you: Time your coffee intake so that you get it either the Italian way, right after, or as in their study right with a potential high MDA meal. Ok, I got to admit this is no exact quotation any longer, but basically it is what they wrote. Plus, this way it spares me to write an extra "bottom line" to which I just have to add that taking up drinking coffee (or tea) if you don't like it is not mandatory to survive meat consumption and that people who suffer from low iron levels should keep in mind that the coffee and tea (and other) phenols will inhibit the absorption of heme- and even more non-heme iron. 

References:

• Botelho F, Lunet N, Barros H. Coffee and gastric cancer: systematic review and meta-analysis. Cad Saude Publica. 2006 May;22(5):889-900. Epub 2006 Apr 28. Review. 
• Ishigaki Y, Katagiri H, Gao J, Yamada T, Imai J, Uno K, Hasegawa Y, Kaneko K, Ogihara T, Ishihara H, Sato Y, Takikawa K, Nishimichi N, Matsuda H, Sawamura T, Oka Y. Impact of plasma oxidized low-density lipoprotein removal on atherosclerosis. Circulation. 2008 Jul 1;118(1):75-83.
• Kanner J, Gorelik S, Roman S, Kohen R. Protection by polyphenols of postprandial human plasma and low-density lipoprotein modification: the stomach as a bioreactor. J Agric Food Chem. 2012 Sep 12;60(36):8790-6.
• Lopez-Garcia E, van Dam RM, Willett WC, Rimm EB, Manson JE, Stampfer MJ, Rexrode KM, Hu FB. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation. 2006 May 2;113(17):2045-53. 
• Sirota R, Gorelik S, Harris R, Kohen R, Kanner J. Coffee polyphenols protect human plasma from postprandial carbonyl modifications.Mol. Nutr. Food Res. 2013; 00: 1–4.
• van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA. 2005 Jul 6;294(1):97-104. Review.
• Williamson G. Possible effects of dietary polyphenols on sugar absorption and digestion. Mol Nutr Food Res. 2013 Jan;57(1):48-57. doi: 10.1002/mnfr.201200511. Epub 2012 Nov 26.
• Wilson KM, Kasperzyk JL, Rider JR, Kenfield S, van Dam RM, Stampfer MJ, Giovannucci E, Mucci LA. Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst. 2011 Jun 8;103(11):876-84.