by Duane Graveline, MD, MPH
The predominant biochemical action of selenium in humans is to serve as an antioxidant via the selenium-dependent enzyme, glutathione peroxidase, and thus protect cellular membranes and organelles from peroxidative damage.
In the absence of this antioxidant, mitochondrial lipid peroxidation results in a marked loss of both cytochrome c oxidase activity and cardiolipin content, offering yet another mechanism by which statins adversely affect mitochondria.
Bottom line of this technical jargon is the reality of more reduced adenosine triphosphate (ATP) and increased mitochondrial damage from reactive oxygen species (ROS).
I have warned in other articles that the primary effect of statins on the mevalonate pathway was to inhibit CoQ10 availability for antioxidation at complexes I and II of the mitochondria.
Now we have identified this second process in which statin inhibition of selenoproteins is involved in mitochondrial change.
This takes place via inhibition of the cytochrome C step in complex III leading to marked loss of cytochrome C antioxidation to spawn even greater effect on aging, chronic disease and mitochondrial mutations. So the ultimate effect on mitochondria is from CoQ10 and selenoprotein inhibition not just CoQ10 alone.
Selenium deficiency has been known for years as a disease of large ruminants. In the UK it has the name of White Muscle Disease (WMD), a degenerative muscle disease caused by a deficiency of selenium in the soils and forage.
Symptoms are those of heart failure and/or generalized muscle weakness. In those parts of the world deficient in selenium, the morbidity from this disease, particularly in sheep and goats, has been extreme and wide-scale use of supplemental selenium is now routine.
Most of the information about the role of selenoproteins in humans has come in the past decade paralleling the marketing of statin drugs. The use of statin drugs has served to increase attention to the role of selenoproteins in humans, since statins tend to block the vital mevalonate pathway by which selenoproteins are utilized.
Current evidence suggests that a daily selenium consumption for humans of approximately 90 micrograms/day/adult should be the minimum daily requirement for optimum biological performance.
Thus far, well over 30 selenoprotein enzymes have been discovered for the element selenium, expressing an unusually wide range of physiologic application with multi-system involvement.
The four glutathione perioxidase enzymes all play various roles as anti-oxidants in the previously mentioned cytochrome C oxidase activity preventing lipid perioxidase formation with its adverse effects due to their high level of reactivity on adjacent tissues.
As such these enzymes are highly beneficial in preventing mitochondrial damage, premature aging and many chronic diseases similar to the antioxidant role of CoQ10.
A main class of selenoproteins are the iodothyronine deiodinase enzymes and another class known as selenocysteine containing enzymes catalyzes the NADPH (nicotinamide adenine dinucleotide phosphate) reaction thereby playing a major regulatory role in its metabolic activity by transferring electrons from NADPH across the inner membrane of the mitochondria and coupling these to molecular oxygen to produce superoxide.
I cite this technical data to illustrate the many diverse and critically important roles of selenoproteins that have been discovered only in the past decade and therefore are unlnown to most physicians.
Statin drugs, by mevalonate blockade and compromise of selenoprotein activity, are proving to have a truly extraordinary reach.
Continuing with known selenium containing substances, 60% of selenium in plasma is incorporated in selenoprotein P and may serve as a transport protein. Selenium W is reported to be necessary for muscle metabolism and another form of selenoprotein is essential for sperm motility.
There is also evidence that selenium has a protective effect against some forms of cancer, that it may decrease cardiovascular disease mortality and be essential for healthy immune response. We are just beginning to understand the various roles of this important element.
The important role of selenium in brain function was first reported by Ramaekers VT and others in Neuropediatrics, 1994 after their successful treatment of two children in the same family with intractable seizures, liver function disturbances and osteoarthropathy, finally diagnosed to be selenium deficient on the basis of blood tests and responding almost immediately to supplemental selenium.
They speculated that two of the seleno-dependent enzymes glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) played a key-role in the defence of neuronal cells against oxygen radical formation and peroxidative processes.
This was supported by the work of Ashrafi MR and others. Epilepsia 48(9), 2007 who in their study of 53 epileptic children, argued that oxidative stress and generation of reactive oxygen species are the cause and the consequence of epileptic seizures, reaffirming the critical role of selenium and glutathione perioxidase activity in the pathogenesis of epilepsy.
The importance of selenium in heart failure was emphasized by Saliba W and others in their report of a case of selenium deficiency induced heart failure reversed after selenium supplementation, published in Int J Cardiol. 2008. They advised that all non-ischemic heart failure patients deserve a serum selenium level measurement as a part of their work up.
The role of selenium in thyroid hormone metabolism was stressed by Nurhan U in Nutrition &Food Science, 2001. Since several selenium containing enzymes are responsible for conversion of the prohormone thyroxine (T4) to the active thyroid hormones (triiodothyronine or T3), consideration must be given to the possible effect of selenium deficiency in interpreting standard thyroid hormone tests.
This is especially true of the elderly. In these cases although a thyroxine (T4) test might be normal, total T3 (and free T3) will be subnormal because the usual conversion of T4 is not taking place. Selenium testing must be done to properly interpret these results but functionally they are hypothyroid, despite normal T4.
In summary, selenium has critical roles in mitochondrial maintenance, muscular metabolism and brain function and is vital in general metabolism and thyroid function, but we are only just beginning to make informed assessments.
Clearly the importance of selenium has been under-estimated in past discussions of statin drug adverse reactions. I must confess that even after creating this review of the important role of selenium, I find myself grasping for real understanding.
Selenium appears to be involved in all of the mechanisms I have so far discovered in explaining other statin drug reactions. One could consider the wide range of effects of aging and come very close to describing the potential effects of deficiency of selenium and selenoprotein.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
Updated August 2016