Friday, June 22, 2012

Can You Bleed Yourself Healthy and Lean? First Controlled Human Trial on the Benefits of Phlebotomy for Glucose and Lipid Metabolism and CVD Risk Could Hold the Answer

Image 1: You better pump iron than "bleed iron" if you want to do something for your health.
Oftentimes the use of supplements that promise to help with all sorts of ailments related to the metabolic syndrome will induce nothing but financial bleeding. The recently published results of an experiment that was conducted by a group of researchers from Germany, on the other hand, suggests that you and make much more progress towards a healthier glucose metabolism, blood pressure and CVD risk profile (Houschyar. 2012).

Donate blood or not, is that the question?

Other than most previous studies, in which scientists had simply discovered a telling association (not even a clear-cut correlation) between glucose resistance / diabetes and the amount of stored iron (ferritin) in the bodies of their mostly obese subjects (Rajpathak. 2009), Houschyar et al. actually set out to test their hypothesis that there is a mechanistic explanation for the striking associations in a randomized controlled trial, involving 25 to 70 year old patients with presumed metabolic syndrome, who had been recruited through advertisements and general (family) practices and complied to at least three of the following criteria
  • abdominal adiposity  as defined by a waist circumference >1020 mm in (menmen; >880 mm (women); 
  • low levels of high-density lipoprotein cholesterol, i.e. HDL-C  < 40 mg/dL (men), <50 mg/dL (women)
  • hypertriglyceridemia indicated by blood triglyceride level >150 mg/dL
  • elevated blood pressure of >130/85 mmHg 
  • impaired glucose homeostasis with fasting plasma glucose >110 mg/dL
Figure 1: Phlebotomy protocol used in the study by Houschyar et al.
After a couple of baseline tests, the 64 subjects which made it into the study were randomized to one of two groups, the
  • iron reduction group, with subjects donating blood at on day 1 and day 28 of the 6 week study period, and the
  • control group, who were offered phlebotomy at the end of the 6-week study period, to ensure compliance (after all, many had applied because they hoped to see improvements in response to the treatment)
Subjects in both groups were advised to keep their habitual diet and take whatever medications they had been on before to minimize the effects of confounding factors.

"Phlebotomy, anyone?" If this was the question your answer should be "YES" if...

... you suffer from high blood pressure, have high blood glucose levels or an undesirable high density to low density lipoprotein (HDL / LDL) ratio, because - as the data in figure 2 goes to show - all those parameters could improve significantly, when you are "550-800ml of blood lighter" ;-)
Figure 2: Change in parameters related to blood pressure, glucose homeastasis, iron and lipoprotein metabolism in active and control arm of the phlebotomy study at the end of the 6-week study period (Houschya. 2012)
This does yet also mean that none of the following parameters showed significant improvements compared to the non-phlebotomized controls:  Insulinadiponectin, hs-CRP, triglyceridescholesterol, HDL-C (absolute) and LDL-C. Which - at least in my humble opinion - raises the question, in how much this "treatment" strategy really is more than just a very temporary bleeding, in the very literal sense, that may be suitable as a headstart into a new, healthier life, but won't render those profound lifestyle changes, people are so hesitant to take, even when their life does depend on them, obsolete.

Causality, statistics and why it always comes full circle to the liver in the real world

Just because a thing has a name, it does not necessarily exist; and as a physicist I'd rather believe in the existence of the Higgs-Boson than in the causal, and not simply corollary involvement / subsequent development of something Dongiovanni et al. refer to as the "dysmetabolic iron overload syndrome" (Dongiovanni. 2011). A syndrome, the 'diagnosis' of which has no real-world significance whatsoever, as its own pathogenesis (i.e. how tis "bad health" effects come about) is intricately entwined with the development of non-alcoholic fatty liver disease (NAFLD) and the liver's subsequent inability to store, release and manage not just iron, but also glucose, lipoproteins (HDL, LDL) and the whole cytochrome P450 enzymatic cascade which keeps your hormones in balance (Gautier. 2011).
Tea and iron levels: For the average Western iron deficiency may not be so much of an issue, but in the developed world and subgroups of our society with suboptimal, not so say insufficient, iron intake, the consumption of large quantities of tea could well turn a marginal into a full blown deficiency (Temme. 2002). On the other hand, an increase in tea consumption and the subsequently reduced iron absorption from the gut could probably reduce the average sedentary meat eater's risk of developing "iron overload" or at least highish iron levels.
This is something the "dysmetablic iron overload syndrome" has in common with another syndrome, you know which? Right! The "metabolic syndrome" - so, if we A begets B and A begets C, will B disappear when we take care of C? No, and guess what: That's exactly what the Houschyar study confirmed. The hilarious reductions in blood pressure, blood glucose and above all HOMA-IR, which were all "statistical significant", but left the study participants still obese, still diabetic and still metabollically messed up were not just without physiological relevance, they are also a necessary not even physiological, but simply physical consequence of the loss of blood. Especially the HOMA-IR, the long term measure of blood glucose loses all its value, when you simply remove the "old" glycated blood cells 2 weeks before the last measurement and thus increases the relative abundance of "fresh" not yet glycated blood cells over baseline.
Figure 2: Percentage of 18- year old future Israeli Special Ops soldiers who developed abnormal hemoglobin (Hb), ferritin, soluble transferrin receptor (sTfR) and transferrin receptor to sTfR/log ferritin ratio (TfR-F index, indicates functional iron deficiency) after 6 months of training (Merkel. 2011)
If you take a closer look at the data in figure 2, you will also see devoted trainees like you, as a SuppVersity reader, either already are, or are just about to become, should probably rather be on the lookout for too low and not to high iron levels, which are, as the study by Merkel et al. clearly shows, nothing only premenopausal women can develop. Even among the 18-year old well-conditioned future Israeli special ops soldiers in the Merkel study, almost 45% ended up with sub-par hemoglobin levels and one fourth with low ferritin levels after 6-months of training. A result which should remind you of one of the recent and increasingly frequent motifs here at the SuppVersity: Don't take the supplements, use the workouts, eat the junk or take the medication or freaky medical treatments that work for your obese neighbor and his comrades in laziness, but pick those that suit you best - and, unless you have hemochromatosis, it's not very likely that phlebotomy is one of them... just like alpha lipoic acid (see "You Could Be Just as Lean, But More Muscular Without ALA"!) and supplemental zinc or ZMA (see "Metabolic Syndrome after 120 Days on 2x RDA of Zinc"), by the way ;-)

  1. Dongiovanni P, Fracanzani AL, Fargion S, Valenti L. Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target. J Hepatol. 2011 Oct;55(4):920-32. Epub 2011 Jun 28.
  2. Gautier A, Lainé F, Massart C, Sandret L, Piguel X, Brissot P, Balkau B, Deugnier Y, Bonnet F. Liver iron overload is associated with elevated SHBG concentration and moderate hypogonadotrophic hypogonadism in dysmetabolic men without genetic haemochromatosis. Eur J Endocrinol. 2011 Aug;165(2):339-43. Epub 2011 Jun 6.
  3. Houschyar KS, Ludtke R, Dobos GJ, Kalus U, Brocker-Preuss M, Rampp T, Brinkhaus B, Michalsen A. Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: Results from a randomized clinical trial. BMC Med. 2012 May 30;10(1):54. [Epub ahead of print]
  4. Merkel D, Huerta M, Grotto I, Blum D, Rachmilewitz E, Fibach E, Epstein Y, Shpilberg O. Incidence of anemia and iron deficiency in strenuously trained adolescents: results of a longitudinal follow-up study. J Adolesc Health. 2009 Sep;45(3):286-91.
  5. Rajpathak SN, Crandall JP, Wylie-Rosett J, Kabat GC, Rohan TE, Hu FB. The role of iron in type 2 diabetes in humans. Biochim Biophys Acta. 2009 Jul;1790(7):671-81. Epub 2008 May 3.
  6. Temme EH, Van Hoydonck PG. Tea consumption and iron status. Eur J Clin Nutr. 2002 May;56(5):379-86.