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The Role of Blood Flow in the Metabolic Syndrome

The metabolic syndrome is one of the most pressing healthcare concerns in the U.S.  This syndrome consists of diabetes, hypertension, hypercholesterolemia, and obesity.  The consequence of the syndrome is increased cardiovascular disease, such as heart attacks and stroke.  A paper published in May 2012 characterized the syndrome as “increasingly prevalent, but poorly understood.”  There is no doubt that the syndrome is increasingly prevalent, but how is that it is poorly understood?  In explaining disease, one of the unfortunate characteristics of biomedical science, since the late 20th century, is to emphasize molecular mechanisms at the expense of an appreciation of the role of blood flow making many disease processes seem mysterious.  This will be a continuing theme in my future commentaries.

Resistance to the effect of insulin is one of the major features of the metabolic syndrome.  Normally, insulin causes cells, especially muscle cells, to take up glucose from the bloodstream.  In the metabolic syndrome, blood glucose levels are increased, and supplemental insulin is only partially effective in decreasing them.  In 1991, Julius et al. proposed that the syndrome is caused by decreased blood perfusion of muscle.  In 1998, Hoiggen et al. demonstrated increased blood viscosity in the syndrome.  Each individual element in the syndrome has also been shown to be associated with increased blood viscosity. 

Because flow is inversely proportional to viscosity, reducing blood viscosity should improve perfusion of muscle and decrease blood glucose levels.  This was confirmed by Houschyar et al. earlier this year.  In their study, the investigators removed between 250cc and 500cc of blood from subjects on two occasions four weeks apart.  This is approximately the same amount of blood removed in a typical donation.  Systolic blood pressure decreased 18.3 mmHg in subjects compared to 0.2 mmHg in controls.  Serum glucose decreased 12.5 mg/dl in subjects, and only 2 mg/dl in controls.  The authors concluded that blood donation may have a beneficial effect in patients with metabolic syndrome.  Curiously, the investigators attributed the beneficial effect to decreased iron stores, not improved blood viscosity and blood flow.  This was based on the idea that excess iron stores cause systemic oxidative stress.  However, oxidative stress has never been demonstrated in humans, only inferred from laboratory experiments. Thus, I prefer to attribute the beneficial effect of phlebotomy to decreased blood viscosity. 

There is a sizable body of work which demonstrates the benefits of blood donation to the donor’s health.  However, you will not see these benefits publicized by the American Red Cross or any other organization which collects and distributes blood for transfusion.  My understanding is that these organizations have decided not to promote the health benefits of blood donation because donations from people who expect to benefit from donating are felt to be less safe than those from donors who only want to help others.   This is why donors of whole blood for transfusion in the U.S. are not paid.     

Hematocrit is the proportion of blood made of the red cells which carry oxygen.  It is the strongest determinant of blood viscosity.  A world class aerobic athlete, such as a cyclist, will need more oxygen- carrying capacity, a higher hematocrit, and thus have higher blood viscosity than an office worker who only exercises casually.  Further, the conditions in which humans evolved are different from those in industrialized society, and the optimal hematocrit and viscosity for the former may be excessive for the latter.  For example, a hunter-gatherer might benefit more from a higher hematocrit than an office worker.   Thus, excessive blood viscosity may be even more prevalent in our society than elevated cholesterol.  The downside of increased blood viscosity is increased workload on the heart and increased mechanical stress on arteries, which accelerates the loss of vascular elasticity.  Cyclic stress causes progressive fracturing of elastic molecules in the arterial wall, and progressive vascular stiffening.  This is an expected consequence of aging but accelerated with increased blood viscosity.  In the future, blood viscosity will be routinely measured and optimized for every individual in order to maximize lifespan.  To paraphrase, the notable physician Sir William Osler, “You are only as young as your vessels.”    

For Further Reading:

A Hoieggen, E Fossum, A Moan, E Enger, and SE Kjeldsen. Whole –blood viscosity and the insulin-resistance syndrome.  Journal of Hypertension 1998;16: 203-210.

KS Houschyar, R Ludtke, GJ Dobos, U Kalus, M Brocker-Preuss, T Rampp, B Brinkhaus, and A Michalsen. Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome:  Results from a randomized clinical trial.  BMC Medicine 2012;10:54.

The full text of both of these papers are available free on the Internet.


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