Thursday, October 3, 2013

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 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.

  • 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.