Hepatitis C, Fatigue and Mitochondria
The most commonly encountered symptom in clinical healthcare settings is fatigue, a problem that plagues a majority of people living with chronic disease. While many mechanisms may be responsible for the fatigue characteristic of the Hepatitis C virus (HCV), one burgeoning theory may have a simple remedy. Possibly due to the medications used to treat it or a direct impact from the virus, chronic HCV is believed to damage the cell’s mitochondria.
Remembering back to high school biology, mitochondria are known as the cell’s power centers. Containing hundreds to thousands of mitochondria in each cell, these organelles are responsible for creating adenosine triphosphate (ATP), molecules that release energy. Scientists believe that a breakdown of the mitochondria’s membrane is a significant factor in mitochondrial damage. Occurring with aging and chronic disease, the breakdown of this membrane directly correlates with a decline in energy levels.
Some of the factors capable of causing damage to the mitochondria include:
- Toxic substances
- Oxidative stress from free radicals
- Viruses that attack membranes
When it comes to living with the Hepatitis C virus, two reasons stand out for causing mitochondrial membrane damage and, therefore, fatigue:
- Drugs used for treatment
- The Hepatitis C virus itself
Drugs: Mitochondrial Toxicity
When medications cause damage to the mitochondria, it is known as mitochondrial toxicity. Used for standard HCV combination therapy, ribavirin is known to be toxic to mitochondria. Ribavirin is a nucleoside analog drug, a class of medications particularly likely to cause mitochondrial damage.
When viruses replicate, a process that involves building new chains of genetic material, viral enzymes may mistakenly add a nucleoside or nucleotide analog onto the chain instead of a normal nucleotide. This mistake causes the viral replication process to grind to a halt. Nucleoside analog drugs can act similarly, interfering with the production of DNA in mitochondria. Unlike other locations for DNA, mitochondria have no mechanism for detecting and fixing such an error. Although potentially able to stop HCV from replicating, nucleoside analogs can also stop the mitochondria from maintaining its longevity.
While severe mitochondrial toxicity is uncommon among those only taking ribavirin, simultaneously taking two or more drugs that can potentially injure the mitochondria poses a much greater risk. People co-infected with HIV/HCV who take ribavirin in combination with anti-retroviral drugs have exhibited more damage to this valuable cell organelle. Some other drugs in use or in development for Hepatitis C that are also nucleoside analogs include:
- Taribavirin (Viramidine) – this drug is a pro-drug of ribavirin, which is converted to ribavirin.
- Polymerase Inhibitors – while not all polymerase inhibitors are nucleoside analogs, valopicitabine (NM283), R-1626 and MK-0608 are.
It has been suggested that the actual Hepatitis C virus itself may contribute to mitochondrial dysfunction. In addition to the potential mitochondrial damage from therapeutic drugs, several studies have suggested that the Hepatitis C virus contributes to this organelle’s deterioration:
- According to a study published in the July 2006 edition of Journal of Virology, researchers reported that HCV infection causes cellular DNA damage and mutations. This injury was confirmed to be mediated by nitric oxide (NO), a substance known to damage mitochondria.
- A recent study found an inverse relationship between HCV viral load and the amount of mitochondrial DNA in peripheral blood mononuclear cells. This means that a rise in HCV viral particles in a person’s system corresponds with fewer functional mitochondria.
- According to a study published in the September 2005 Journal of Biological Chemistry, a Hepatitis C viral protein directly affects mitochondria. By looking at the oxidative stress caused by free radicals, researchers concluded that antioxidant therapy may defend against some of HCV’s damage to mitochondria.
Preventing mitochondrial cell membrane damage and loss of membrane integrity are important for averting the loss of cellular energy. One popular method that has been used to replace damaged components of the mitochondrial membrane is replacement therapy. By replacing the damaged lipids with phospholipids and fatty acids essential to the structure and function of biological membranes, restoration of the mitochondria’s boundaries is possible.
The first outward sign of mitochondrial membrane deterioration is likely to be fatigue. Damage to the mitochondrial membrane results in the following cascade of events:
- Its phospholipid structure loses fluidity which leads to…
- An increasingly porous membrane which leads to…
- A reduction in the membrane’s electrical potential which leads to…
- A decreased capability of making cellular energy.
Using lipid replacement therapy, the innovation of NT Factor® has been successful in repairing the mitochondrial membrane and restoring people’s energy levels. Shown in clinical studies to increase participant’s energy by up to 40 percent, NT Factor® has helped many people combat the mitochondrial membrane’s decline. With the ability to strengthen this important membrane, the mitochondria become more resilient to nucleoside analogs and virally-induced damage – thus preserving a person’s energy.
Affecting between 65 and 75 percent of people with HCV, profound fatigue is a likely result of a deficiency in the mitochondria. Helping to sustain the fluidity of cell’s mitochondrial membranes has the direct result of maintaining youthful vigor. Whether due to aging, medications or a result of HCV, consider lipid replacement therapy as a means to energize your mitochondria and abandon excessive tiredness.
Agadjanyan, Michael, PhD, Garth L. Nicholson, PhD, et al., Nutritional Supplement (NT Factor™) Restores Mitochondrial Function and Reduces Moderately Severe Fatigue in Aged Subjects, Journal of Chronic Fatigue Syndrome, 2003.
Machida K., et al., Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation, Journal of Virology, July 2006.
Masaaki Korenaga, et al., Hepatitis C virus core protein inhibits mitochondrial electron transport and increases ROS production, Journal of Biological Chemistry, September 2005.
Okuda M., et al., Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein, Gastroenterology, February 2002.
www.hcvadvocate.org, Mitochondrial Toxicity, Liz Highleyman, Hepatitis C Support Project, August 2007.