Monday, March 24, 2014

If Insulin Sensitivity is Key, What's the Key to Insulin Sensi- tivity? Artemisia Dracunculus, Lixisenatide, Calcium & Bi- carbonated Water - True Promoters of Insulin Sensitivity?

Insulin sensitivity is a necessary pre- requisite for much more than a profane set of sixpack abs.
You will probably have realized that the number of short-news like articles on the SuppVersity has been increasing as of late. The reasons for that are twofold: For one, it's the fact that it pisses me off (sorry, but that's how it is) that all the interesting stuff I post on the SuppVersity Facebook Page disappears into an oblivion of which I can only hope that it is not Mark Zuckerberg's *** Secondly, I am currently working my regular job, doing some additional University stuff and working on another nutrition and exercise science related project and don't have the time to do the extensive research that's necessary to produce articles like part II of the "perfect frying oil" article, you may (rightly) already be waiting for.

In other words: If you don't want me to switch to a twice or thrice (max) a week schedule, you will have to live with less in-depth articles like this - sorry! If you would prefer a new schedule, on the other hand, let me know.

Artemisia dracunculus and Lixisenatide, two names to remember?

Actually the first of these names, namely Artemesia dracunculus is a herb you should be vaguely familiar with, if you remember an old SuppVersity article with the title "SuppVersity Supplement Scrutiny: Athletic Edge Nutrition Creatine RT - More Than Yet Another Marketing Gag?" (refresh your memories). In said article I acknowledged the insulin-sensitizing prowess of Tarragon extract, but doubted that its purported effects on the uptake of creatine into the muscle had any real-world relevance.

I guess, some of you will probably say the same of the observation that the tarragon bioactives "improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines" in a recent in vitro study by scientists from the Louisiana State University. Before you do so, I would yet like to remind you of the existing evidence that supports the insulin-sensitizing (Wang. 2011), muscle-preserving (Kirk-Ballard. 2013), anti-diabetic (Watcho. 2010; Eisenman. 2011;  Scherp. 2012),  as well as anti-NAFLD (Wang. 2013) and eye (Watcho. 2011) and nervous system protecting (Singh. 2014) effects of this herb.

If you still don't trust a supplement that failed you once,...

there is obviously still BigPharma's answer to herbal supplements: Lixisenatide, a synthetic GLP-1 analogon that has just demonstrated that it could be the future of (type II) diabetes treatment.

Lixisenatide comes in a fool-proof pen - what else?
In a study that was conducted by no one else than the inventors over at Sanofi-Aventis in Frankfurt, Germany, injecting the drug subcutaneously 2 hours before an intravenous glucose challenge accelerated the disposal of glucose to "nearly physiological intensity" (Becker. 2014) - in other words: The mere injection of the GLP-1 analog reduced the insulin requirements of the diabetics to zero and helped push the glucose into the cells at a rate that's identical to the one of non-diabetics.

In view of the fact that it did not impair the counter-regulation to low glucose levels by glucagon, it's probably just feasibility question (can you time it properly), if and when at least some diabetics will have Lixisenatide pens (see image to the right), instead of insulin syringes in the neat "I want that piece of cake now, so I have to inject tons of insulin"-bags they are carrying wherever they go.

And if you don't do drugs, ...

... a very simple and, as a recent study appears to confirm, effective way to improve your glucose management would be to increase your intake of calcium containing foods and/or "hard" (=high calcium) water around meals.
Don't forget your bicarbonated mineral water folks! It's not calcium, but it works wonders: Sodium bicarbonate - In a 2007 paper, researchers from the Spanish Council for Scientific Research report that the consumption of 0.5l of sodium-rich bicarbonated mineral water with a standard fat-rich meal lead to significantly reductions in postprandial insulinemia in postmenopausal women compared to the same meal with regular water (Schoppen. 2007).
Why? Well, as a SuppVersity veteran you should actually remember that rumors had it for years that a high calcium intake would help with weight loss, but the observations in corresponding experiments were mixed and the contemporary scare about the connection between calcium supplements, on the one hand, and cardiovascular heart disease (CHD) and/or prostate cancer, on the other hand, put another question-mark, this time one that corresponds to safety issues, behind the "calcium for weight loss" paradigm.
Figure 1: Relative serum / blood levels of GIP, GLP-1, insulin, glucose, lactate and NEFA after meals with high calcium content compared to isocaloric meal w/ identical macronutrients w/ low calcium (Gonzalez. 2013).
Now, the results of a recent study from the Northumbria University in the UK won't make this question.mark disappear. What they definitely do, though, is clarify the underlying mechanism of action, which is - and this should be obvious, when you look at the data in Figure 1 - mediated by the calcium-induced 47 % and 22 % increases in GIP1–42 and GLP-1 respectively (Gonzalez. 2013).
Figure 2: Overview of the purported anti-obesity + anti-diabetic effects of calcium + vitamin D (Soares. 2014)
In conjunction with the 19 % increase in insulin areas under the curve for the 120 min following consumption of the macronutrient-matched meals these hormonal changes induced a 12 % reduction in appetite in the 10 healthy male subjects.

The combination of increased insulin levels and improved blood glucose clearance, on the one, and an increased production of the fat-burning satiety hormone GLP1, on the other hand, renders these observations interesting for both: The overweight, insulin resistant couch potato and the normal-weight individual on his / her way to a physique model body.
Figure 2: The increased bioavailability of citrate-bound calcium Sakhaee et al. calculated based on a meta- analysis of 15 studies (184 subjects) suggests that calcium citrate would be your preferential calcium source - and that irrespective of whether you're takin' it with meals or on empty  (Sakhaee. 1999).
Bottom Line: After my recent post about the beneficial effects of sufficient and the questionable benefits of additional calcium intake in Part IV of the"There is More To Glucose Control Than Carbohydrates"-Series (read all installments), I am very hesitant to suggest adding another calcium carbonate or citrate tablet on top of the 200mg of calcium you got from the whey protein you have had after your workout today and the 400mg of calcium that's in the micellar casein you are about to sip before you collapse into your bed, later today.

In case you are missing out on these high protein calcium, sources, don't guzzle calcium containing mineral (in German tap water) and have a low intake of green leafy veggies and other high calcium food, there may however be room for additional 400mg calcium citrate (you can buy that for a few pennies as powder in an animal food store, if you don't have the bucks for the expensive tablets) in your supplement regimen. And yes, I think that's more useful than artemisia or GLP-1 analogues.
  • Becker, et al. "Lixisenatide Resensitizes The Insulin-Secretory Response To Intravenous Glucose Challenge In People With Type 2 Diabetes – A Study In Both People With Type 2 Diabetes And Healthy Subjects." Diabetes, Obesity and Metabolism (2014) - Accepted Article.
  • Eisenman, Sasha W., et al. "Qualitative variation of anti-diabetic compounds in different tarragon (Artemisia dracunculus L.) cytotypes." Fitoterapia 82.7 (2011): 1062-1074. 
  • Gonzalez, Javier T., and Emma J. Stevenson. "Calcium co-ingestion augments postprandial glucose-dependent insulinotropic peptide1–42, glucagon-like peptide-1 and insulin concentrations in humans." European journal of nutrition (2013): 1-11.
  • Kirk-Ballard, Heather, et al. "An extract of Artemisia dracunculus L. inhibits ubiquitin-proteasome activity and preserves skeletal muscle mass in a murine model of diabetes." PloS one 8.2 (2013): e57112.
  • Scherp, Peter, et al. "Proteomic analysis reveals cellular pathways regulating carbohydrate metabolism that are modulated in primary human skeletal muscle culture due to treatment with bioactives from< i> Artemisia dracunculus</i> L." Journal of proteomics 75.11 (2012): 3199-3210.
  • Sakhaee, Khashayar, et al. "Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate." American journal of therapeutics 6.6 (1999): 313-322.
  • Singh, Randhir, Lalit Kishore, and Navpreet Kaur. "Diabetic peripheral neuropathy: Current perspective and future directions." Pharmacological Research 80 (2014): 21-35. 
  • Soares, Mario J., Kaveri Pathak, and Emily K. Calton. "Calcium and Vitamin D in the Regulation of Energy Balance: Where Do We Stand?." International Journal of Molecular Sciences 15.3 (2014): 4938-4945.
  • Vandanmagsa, B. et al. "Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture." Diabetes, Obesity and Metabolism (2014) - Accepted Article.
  • Wang, Zhong Q., et al. "An extract of Artemisia dracunculus L. enhances insulin receptor signaling and modulates gene expression in skeletal muscle in KK-A y mice." The Journal of nutritional biochemistry 22.1 (2011): 71-78.
  • Watcho, Pierre, et al. "High-fat diet-induced neuropathy of prediabetes and obesity: effect of PMI-5011, an ethanolic extract of Artemisia dracunculus L." Mediators of inflammation 2010 (2010).
  • Wang, Zhong Q., et al. "< i> Artemisia scoparia</i> extract attenuates non-alcoholic fatty liver disease in diet-induced obesity mice by enhancing hepatic insulin and AMPK signaling independently of FGF21 pathway." Metabolism 62.9 (2013): 1239-1249.
  • Watcho, Pierre, et al. "Evaluation of PMI-5011, an ethanolic extract of Artemisia dracunculus L., on peripheral neuropathy in streptozotocin-diabetic mice." International journal of molecular medicine 27.3 (2011): 299-307.