Ubiquitous

u-biq-ui-tous- adjective: existing or being everywhere, esp. at the same time; omnipresent

Coenzyme Q10, also known as ubiquinone, is the Lady Gaga of herbal supplements. New to the scene, kind of different, really interesting, has potential for a lot of great things, but no one seems to know what to make of it.

Ubiquinone has been known to biochemists for years, but the concept of using it as a dietary supplement came about relatively recently.

So... what is coenzyme Q10? The name is appearing more and more in the aisles of pharmacies and health food store and its celebrity as a supplement rivals that of vitamin D. However, coQ 10 is not a vitamin; it is naturally synthesized in the human body (in contrast to a vitamin, which is obtained through diet).

CoQ is a bright orange, lipophilic substance that acts as an antioxidant and plays a major role in oxidative phosphorylation in mitochondria. It resides in the inner layer of the lipid bilayer membrane of mitochondria and accepts electrons from NADH. Protons are then pumped from the mitochondrial matrix into the inter membranous space, creating an electrical gradient. As protons cross back though the membrane, they pass through a proton channel where ATP synthase uses the energy to add a phosphate group to ADP, creating ATP, the energy currency of cells. Coenzyme Q has also been shown to regenerate active forms of the vitamins E and C. Its reduced form, ubiquinol, is present in all tissues.

Circa 1990, it was discovered that HMG-CoA reductase inhibitors (aka statins), designed to inhibit the production of LDL cholesterol, also inhibited the synthesis of coenzyme Q10. Additionally, LDL cholesterol serves as a transporter of coenzyme Q, therefore reductions in LDL would also theoretically reduce the amount of coenzyme Q in blood circulation. As a result, it was hypothesized that repleting CoQ could eliminate some of the side effects associated with statin therapy; namely, myalgias and rhabdomyolysis.

The mechanism for statin induced myalgias is still unknown, but it has been hypothesized that the reduction in coenzyme Q10 may, at least, be a contributing factor. Studies subsequently showed that CoQ supplementation could replete plasma and muscle levels of coenzyme Q, however, they failed to show a reduction in myalgias. Mabuchi et al concluded in 2007 that reduction in CoQ levels was a primary effect of statins and that supplementation with 100 mg/day of CoQ significantly boosted plasma levels. There was, however, no significant difference in myalgias or liver function tests.

In 2007, Marcoff and Thompson’s meta-analysis published in the Journal of the American College of Cardiology, carefully dissected the outcomes of studies and showed that a lot of questions remain unanswered. There have been very few studies specifically looking at muscular levels of coenzyme Q10 in patients with statin induced myalgias, and the question of whether decreased coenzyme Q10 levels can cause mitochondrial dysfunction remains unanswered despite some preliminary studies. Additionally, the meta-analysis failed to demonstrate a clear benefit though the use of coenzyme Q10 supplementation in patients taking a statin.

Despite the plethora of small trials examining coenzyme Q supplementation, larger and better powered trials are needed. As it stands, coenzyme Q is not recommended with statin therapy or as a treatment for statin induced myalgias.

References:
Meisenberg G, Simmons WH. Principles of medical biochemistry. 2nd ed. Mosby-Elsevier 2006.

Mabuchi H et al. Effects of CoQ10 supplementation on plasma lipoprotein lipid, CoQ10 and liver and muscle enzyme levels in hypercholesterolemic patients treated with atorvastatin: a randomized double-bling study. Atherosclerosis 2007;195:e182-e189.

Marcoff L, Thomson MD. The role of coenzyme Q10 in statin-associated myopathy: a systematic review. Journal of the American College of Cardiology 2007;49(23):2231-7.

Wynn RL. The effects of CoQ10 supplements on patients taking statin drugs. General Dentistry 2010;58(3):168-170.

Akhenaten & Vitamin D

As a native Californian, I have grown up worshiping the sun, and really, who doesn’t?  The star to which we owe our very existence and worshiped in ancient cultures.  The Egyptian pharaoh preceding Tutankhamun even banned the worship of any other god BUT Aten, the sun disk, and renamed himself “AkhenATEN”.  Providing more than just warmth and great beach days, the sun allows the occurrence of certain essential biochemical processes, such as photosynthesis and the production of vitamin D.

Vitamin D is a lipid soluble vitamin that can be obtained through dietary means, or through sun exposure.  UV-B rays penetrating the skin catalyze the production of a pre-cursor to vitamin D, which then must travel to the liver then the kidneys for activation.  Maintaining adequate vitamin D levels has been associated with decreased risks of breast and colorectal cancers, psychiatric disorders, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes. Vitamin D inhibits renin production in the kidneys, has immunomodulatory effects on lymphocytes, and increases the absorption of calcium in the gut.

Most people immediately think of bones when calcium comes to mind.  However, calcium is an essential element in many biological processes, such as muscle contraction and heart conduction.  As a result, it is essential that levels of calcium within the blood are maintained within a specific range.  High levels of calcium results in excessive thirst, and can eventually cause lethargy, muscle weakness, and heart rhythm changes.  Low levels may result in stiff aching muscles and confusion. 

Under non-pathological conditions, excess serum calcium is moved into the bones out of the circulation and low circulating calcium causes calcium leaching from the bones through signaling from parathyroid hormone and calcitonin.  Long term leaching of calcium from the bones to maintain adequate concentrations of calcium in the blood stream eventually leads to osteopenia and osteoporosis.  Vitamin D also helps to increase absorption of calcium.

In July 2010, the Boston Medical Journal published the shocking results of a meta-analysis by Bolland et al.  The final analysis compiled data from 11 double blind randomized control trials where subjects took calcium without vitamin D compared to placebo.  The trial showed a statistically significant increase in heart attacks for patients supplemental calcium (HR 1.31, p0.035), although no statistically significant increase in risk of death. 

Further analysis showed that the risk was increased only when daily intake was above 805 mg/day of calcium, which is still only a moderate dose.  Rather than proving that calcium supplementation is bad, this study demonstrates the importance of vitamin D, which had been excluded from the study due to previous analyses showing decreased mortality with vitamin D supplementation with calcium. 

In response to patient concerns that calcium supplementation will increase their risk of myocardial infarction (aka heart attack or MI), I would suggest that patients taking calcium supplements ensure that they are getting adequate vitamin D from the sun, dietary intake or supplements.  Further studies and analyses are needed to show specifically what recommendations health care providers can make to keep patients safe as well as to fully understand the reason for increased risk of MI.

Vitamin D supplementation has become the latest hot topic; as such there is a variety of literature covering many different benefits it may provide.  For the sake of time and entry length, I will cover one more article published in July 2010 in AIDS.

Previous literature reported high rates of vitamin D deficiency in patients living with HIV/AIDS, so Welz and colleagues set out to examine potential risk factors in HIV positive patients.  Results of the study indicated that the winter season (when patients are exposed to less sun), black ethnicity (a patient population that needs longer sun exposure to produce adequate vitamin D), CD4 count nadir of less than 200 cells/mcL, and a medication regimen containing efavirenz were associated with vitamin D deficiency.  Age, sex, renal function, and other anti-retroviral medications were not associated with increased risk.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor recommended in combination with two medications from the NRTI class as one of the first line regimens for treatment-naïve patients with HIV.  It is a component of the first ever one pill a day anti-retroviral regimens and is not associated with fat redistribution, as seen with the buffalo hump formation after use of protease inhibitors. 

This trial indicates that it may be beneficial for patients taking efavirenz to take moderate daily supplementation of vitamin D to avoid long-term complications of vitamin D deficiency and for cardiovascular protection.

Akhenaten may have not known about the existence or biochemical significance of vitamin D, he was most certainly correct in proclaiming the sun the most important “god” for ensuring life on earth.

References:

Mayo Clinic electronic resource.  http://www.mayoclinic.com/health/vitamin-d/NS_patient-vitamind accessed 8/12/2010.

The Merck Manuals: online medical library.  http://www.merck.com/mmhe/sec12/ch155/ch155b.html accessed 8/12/2010.

Booth M.  The secret history of the world.  The Overlook Press NY; 2008.

Holick MF et al.  Vitamin D deficiency: a worldwide problem with health consequences.  American Journal of Clinical Nutrition 2008;87(4):1080S-6S.

Bolland MJ et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis.  BMJ 2010;341:c3691.

Welz T et al.  Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase.  AIDS 2010;24(12):1923-1928