Friday, November 29, 2013

Artichoke Leaves Diabetes No Chance: Thistle Qualifies as Anti-Oxidant, Carb Blocker, Digestive Help & Diabesity Drug

Boiled Artichokes slow down the absorption of glucose and minimize the insulin + glucose surges (Nomikos. 2007)
This article has made quite a remarkable transformation. It started as a Facebook Short News Item, was upgraded to a mini-article for the SuppVersity Short News and, when I realized that those green thistles have surprisingly diverse beneficial effects on human health, eventually became the regular SuppVersity Article you are about to read, right now.

Artichoke leaves the future of diabesity treatment!?

I have to admit, I am not exactly and artichole expert, but I was still surprised that the paper Joanna Magielse and her colleagues from the University of Antwerp are about to publish in the scientific journal Food & Function claims to be the first to investigate the beneficial health effects of artichoke leave extracts on diabetes-induced oxidation in vivo.

I mean, we all have seen the broad range of artichoke supplements on the shelves; and my brief review of the literature yielded studies from the mid 1920s discussing how beneficial artichoke can be for patients with type II diabetes (Root. 1925).

When I kept digging through the currently available literature, though, I had to realize that the vast majority of the in-vivo studies dealt with the anti-cholesterol (Wider. 2013) and digestive benefits (Marakis. 2002) of artichokes and their leaf extracts (ALE). The proven anti-oxidant effects of its major polyphenolic constituents (Zapolska-Downar. 2002;  Betancor-Fernandez. 2003; Jimenez-Escrig. 2003; Menghini. 2010), on the other hand, haven't been tested in either animals or humans with type II diabetes. The rodent-experiment the Belgian researchers describe in the paper at hand is thus probably in fact the first to investigate the anti-oxidative effects ALE in an in-vivo scenario.
More about chlorogenic acid.
What are the active ingredients in artichoke leaves? Mono- and dicaffeoylquinic acids were the major polyphenolic constituents: The total caffeoylquinic acid (CQA) content was 1.5%, with chlorogenic acid (CGA) being most abundant (0.30%), next to cynarin (0.12%) and several isomerization products of CGA (the sum of which was 0.75%), including neo- and crypto-CGA and dicaffeoylquinic acids. Luteolin-7-O-glucoside was the major flavonoid present.
Over the course of 3 weeks the rodents who had been injected with streptozotocin (STZ) to induce a diabetic phenotype that is commonly and successfully used as a model for type II diabetes in man consumed either
  • Why 0.2g/kg BW? This is the rodent equivalent of a well-tolerated amount of 2g/day that has been used for treatment of hypercholesterolemia and digestive complaints (Englisch. 2000; Holtmann. 2003; Barnes. 2007).
    0.2g/kg BW of artichoke extract (CYN1),
  • 1g/kg BW of artichoke extract (CYN2),
  • 50mg/kg BW alpha-tocopherol-acetate (VIT E),
or no supplement at all. To make sure to have an appropriate reference, a fifth non-streptozotocin injected group served as a healthy control. In contrast to their their com-rats (sorry, I could not resist) who had blood glucose levels of 250mg/kg, the control rats started into the 3-week treatment phase with normal (=healthy) blood glucose levels and inflammation.
Learn About Artichoke Alternatives for Glucose Management:

Lifestyle Changes

ALA, GABA, Taurine & Co.

Berberine, Banaba & Co.

Cinnamon, Curcumin & Co.

Lemon, Starch, Coffee & Co.

Chlorogenic acid, fucoxanthin & Co.
To determine the effects the provision of artichoke leaves would have on the baseline inflammation of the diabetic rats, the researchers measured the plasma malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG). The status of plasma coenzyme Q9(CoQ9, necessary for the biosynthesis of coq10 increases indicate lower coQ10 levels) and erythrocyte reduced glutathione (GSH), on the other hand, were used as indicators of the state of the endogenous antioxidative defense system.
Figure 1: MDA, 8-OHdG, CoQ9 and GSH levels expressed as rel. difference to control (Magielse. 2013)
With the information from the previous paragraph, even a rocket scientist without a clue of biology will recognize that the buffered MDA,8-OHdG and coQ10 and GSH levels (the further away from the x-axis the more "disturbed" they are compared to the CON group), indicate that the artichoke leave extract did what the were not 100% sure it would to: It survived the passage through the gastrointestinal tract and wasn't extensively metabolized by colonic microflora or liver phase II enzymes, as it is the case for other potent in-vitro antioxidants like reseveratrol.

What's the mechanism and what do we already know about artichoke?

With respect to the underlying mechanism that could explain the improvements the researchers observed in the study at hand, Magielse et al. point out that...
"...it should be emphasized that not only direct antioxidant actions, but also indirect mechanisms affecting gene expression of inflammatory pathways and modulating antioxidant enzyme synthesis have been reported for polyphenols and may contribute to the reduction of oxidative stress." (Magielse. 2013)
In that, the scientists are referring to the previously established beneficial effects on lipid metabolism and glucose absorption other researchers have observed in previous studies:
  • Boiled wild artichoke reduces postprandial glycemic and insulinemic responses in normal subjects by inhibiting the glucose absorption (100g of boiled plant on 50g of glucose in complete meal). Interestingly, this trick doesn't work in patients with type II diabetes (Nomikos. 2007)
  • Significant increase in bile secretion and thus improved fat digestion.  1.92g of artichoke extract lead to increase of up to ~140% in a randomised placebo-controlled double-blind cross-over study published in Phytomedicine (Kirchhoff. 1994). 
  • Beneficial improvements in endothelial function (-21% VCAM-1; - 17% ICAM-1 brachial +37% FMV) in hyperlipidemic patients with only 20ml of "self-made"* artichoke juice per day (*juiced by the researchers; Lupattelli. 2004).
  • Provides "food" for probiotic Lactobacillus paracasei (LMGP22043) that have beneficial effects on faecal bacteria and biochemical parameters in human subjects (Valerio. 2011).
  • Has UV protective effects, when applied to the hair (Fernandez. 2012) - not that important for your overall  health, but still quite telling, right?)
  • 2x 200mg of ALE per day decrease total cholesterol and LDL and increase HDL in subjects with existing hypercholesterolaemia (Rondanelli. 2013)
I know that you'd probably love another 200 references to studies that support the beneficial health effects of artichoke and artichoke extracts, but you know what? I think that's enough for a preliminary conclusion.
Diabetes or Not-Diabetes - That's not just about the foods you eat, but also about what your body does with them: "Dietary Fructose vs. Endogenous Fructose Production: Is The Aldose Reductase Mediated Production of Fructose to Blame for Diabesity & NAFLD? Could Amla Help? " | more
Bottom line: With the existing evidence for its acute anti-hyperglycemic effects, its beneficial effects on lipid digestion and metabolism and reliable evidence from a 2005 study by Wittemer that the antioxidant caffeoylquinic acids and flavonoids are orally bioavailable in humans (Wittemer. 2005), it appears as if artichokes would make a a highly underrated, yet profoundly beneficial addition to everyone's diet.

With commercially prepared extracts, on the other hand, you do not just run the risk of buying not / incorrrectly standardized products without active ingredients, but could also be missing out on the actue anti-hypoglycemic effects, which are probably mediated by the fructan-content of the whole "fruit"; not the caffeoylquinic acids and flavonoids you can buy in capsule-, pill- or tablet-form (cf. Rumessen. 1990; the dosage of fructans that did the trick here was 20g!)

Reference:
  • Barnes, J., Anderson, L.-A., Phillipson, J.-D. (Eds.), Herbal Medicines, Pharmaceutical Press, London 2007. 
  • Betancor-Fernandez, A., P´ erez-G´ alvez, A., Sies, H., Stahl, W., Screening pharmaceutical preparations containing extracts of turmeric rhizome, artichoke leaf, devil’s claw root and gar lic or salmon oil for antioxidant capacity. J. Pharm. Pharma col. 2003,55, 981–986. 
  • Englisch, W., Beckers, C., Unkauf, M., Ruepp, M. et al., Effi cacy of artichoke dry extract in patients with hyperlipopro teinemia. Arzneimittel-Forschung. 2000,50, E260–E265. 
  • Fernandez, E., Martínez-Teipel, B., Armengol, R., Barba, C., & Coderch, L. Efficacy of antioxidants in human hair. Journal of Photochemistry and Photobiology B: Biology.  2012
  • Holtmann, G., Adam, B., Haag, S., Collet, W. et al., Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six-week placebo-controlled, double blind, multicentre trial.Aliment. Pharmacol. Ther. 2003,18, 1099–1105.
  • Jimenez-Escrig, A., Dragsted, L.-O., Daneshvar, B., Pulido, R. et al., In vitro antioxidant activities of edible artichoke (Cynara scolymusL.) and effect on biomarkers of antioxi dants in rats.J. Agric. Food Chem. 2003,51, 5540–5545.
  • Kirchhoff, R., Beckers, C. H., Kirchhoff, G. M., Trinczek-Gärtner, H., Petrowicz, O., & Reimann, H. J. Increase in choleresis by means of artichoke extract. Phytomedicine. 1994, 1(2), 107-115.
  • Lupattelli, G., Marchesi, S., Lombardini, R., Roscini, A. R., Trinca, F., Gemelli, F., ... & Mannarino, E. Artichoke juice improves endothelial function in hyperlipemia. Life sciences. 2004, 76(7), 775-782.
  • Marakis, G., Walker, A. F., Middleton, R. W., Booth, J. C. L., Wright, J., & Pike, D. J. (2002). Artichoke leaf extract reduces mild dyspepsia in an open study. Phytomedicine, 9(8), 694-699.
  • Menghini, L., Genovese, S., Epifano, F., Tirillini, B. et al., Antiproliferative, protective and antioxidant effects of arti choke, dandelion, turmeric and rosemary extracts and their formulation.Int. J. Immunopathol. Pharmacol. 2010,23, 601– 610. 
  • Nomikos, T., Detopoulou, P., Fragopoulou, E., Pliakis, E., & Antonopoulou, S.. Boiled wild artichoke reduces postprandial glycemic and insulinemic responses in normal subjects but has no effect on metabolic syndrome patients. Nutrition Research. 2007, 27(12), 741-749.
  • Root, H. F., & Baker, M. L. Inulin and artichokes in the treatment of diabetes. Archives of Internal Medicine. 1925, 36(1), 126.
  • Rondanelli, M., Giacosa, A., Opizzi, A., Faliva, M. A., Sala, P., Perna, S., ... & Bombardelli, E. (2013). Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, placebo-controlled trial. International Journal of Food Sciences and Nutrition, 64(1), 7-15.
  • Rumessen, J. J., Bodé, S., Hamberg, O., & Gudmand-Høyer, E. Fructans of Jerusalem artichokes: intestinal transport, absorption, fermentation, and influence on blood glucose, insulin, and C-peptide responses in healthy subjects. The American journal of clinical nutrition. 1990, 52(4), 675-681.
  • Valerio, F., et al. Role of the probiotic strain Lactobacillus paracasei LMGP22043 carried by artichokes in influencing faecal bacteria and biochemical parameters in human subjects. Journal of applied microbiology 2011, 111(1): 155-164.
  • Wider, B., Pittler, M. H., Thompson-Coon, J., & Ernst, E. (2013). Artichoke leaf extract for treating hypercholesterolaemia. status and date: New search for studies and content updated (no change to conclusions), published in, (3).
  • Wittemer, S. M., Ploch, M., Windeck, T., Müller, S. C., Drewelow, B., Derendorf, H., & Veit, M. Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans. Phytomedicine. 2005, 12(1), 28-38.
  • Zapolska-Downar, D., Zapolski-Downar, A., Naruszewicz, M., Siennicka, A. et al., Protective properties of artichoke (Cynara scolymus) against oxidative stress induced in cultured endothelial cells and monocytes .Life Sci.2002,71, 2897–2908.