Reduce Oxidative Stress : CerefolinNAC
A medical food for the dietary management of neurovascular oxidative stress and/or hyperhomocysteinemia.
Reduce Oxidative Stress
What is Oxidative Stress?
Oxidative stress is the condition created due to the accumulation and action of free radicals in the body's cells. Free radicals are damaging, unbalanced oxygen containing molecules. Reactive oxygen species (ROS) is a term collectively used to describe free radicals containing oxygen. Oxidative stress occurs when the generation of ROS in a system exceeds the body's ability to neutralize and eliminate them thus creating an imbalance or over abundance of free radicals. This imbalance can result in a lack of antioxidant capacity. Antioxidants are the body's mechanism to neutralize ROS. If not regulated properly, excess ROS can damage a cell's lipids, protein or DNA and disturb normal function. Some examples of ROS are superoxide, hydrogen peroxide, and lipid peroxide. Studies suggest that oxidative stress is present in the brain of patients with early memory loss, suggesting that oxidative damage may be an initial event in the onset and progression of Alzheimer's disease. 1 2
Although the etiology of Alzheimer's disease remains largely unclear, there is accumulating evidence that oxidative stress plays an important role in the disease pathophysiology. However, intracellular oxidative balance is tightly regulated and, therefore, the activation of multiple signaling pathways and up-regulation of compensatory mechanisms would be expected to occur in neurons. Research reports cells that fail to compensate for oxidative imbalance enter into apoptosis, which in turn leads to death within hours. Following this point of view, cells can only experience oxidative stress for short periods of time without rapidly dying.
With the broad occurrence of AD (almost 50% by the age of 85), the nonregenerative nature of the central nervous system and the fact that diagnosis often does not occur until late in disease progression, suggest that the ideal time for antioxidant therapy is in preventative treatment of early stages of memory impairment. Due to low toxicity, ease of administration and the ability to target the earliest sources of oxidative stress in AD, an agent like Cerefolin®NAC may be appropriate.
This graph represents technical information presented in: Brumback RA and Leech RW. Alzheimer's Disease: Pathophysiology and the Hope for Therapy. J. Okla State Med Assoc. 1994; 87:103-111
How Free Radical Damage Begins3
In a stable molecule, the core is surrounded by pairs of negatively charged electrons. Remove one electron of a pair, a process called oxidation, and the molecule becomes unstable and destructive. The name of this new molecule is "free radical" and it is on a collision course with DNA, protein and fat molecules.
Free Radical Damage to Stable Molecules
Obsessed to recapture balance, the free radical collides with stable molecules that make up DNA, protein and fat in the cells of the body. This collision recaptures the lost electron. Molecule provides this electron. The free radical becomes a balanced molecule once again. The harmless molecule is transformed into a free radical and the cycle begins anew.
Free radicals increase when there are not enough antioxidants to neutralize them. The result of free radicals stealing electrons from healthy cells is damaged DNA, damaged protein molecules that make up many components of the cell and damaged fat molecules in the outer membrane that protects the cell. More than ever before, the body needs "peacemakers," or molecules equipped to end the chain reaction. Antioxidants are uniquely designed for the job.
Antioxidants Neutralize Free Radicals
Binding together, the antioxidant reinstates the free radical back to an electron balance, halting the perpetuation of a health threat. Any molecule that collides with a free radical, terminating this harmful oxidative stress, is an antioxidant. Though inactivated by this work, the antioxidant may be reinstated or retire.
Normally, bonds don't split in a way that leaves a molecule with an odd, unpaired electron. But when they do, highly reactive free radicals are formed. Free radicals are very unstable and react quickly with other compounds, trying to capture the needed electron to gain stability. Free radicals attack the nearest stable molecule, "stealing" its electron. When the "attacked" molecule loses its electron, it becomes a free radical itself beginning a chain reaction, or it may die. The process continues until free radicals are stabilized by a chain-breaking antioxidant such as glutathione. Once the process is started, it can cascade and result in the disruption of a living cell. This cascade may contribute to neurodegenerative disease such as Alzheimer's.
Many free radicals are the result of naturally occurring processes. When cells use oxygen to generate energy during metabolism, free radicals are created. Oxidative stress occurs when there are too many pro-oxidant free radicals, and the balance between pro-oxidants and antioxidants is lost. Certain organ systems are predisposed to greater levels of oxidative stress. The brain is one of the organ systems most susceptible to damage by free radicals because of its intense metabolic activity and high requirement for oxygen. Neurons under sustained oxidative stress lose their connections and communication with other neurons and the ability to perform their functions.
The Damage of Oxidative Stress
The damage of oxidative stress is a key feature in the brains of Alzheimer's patients. Researchers have discovered that accumulations of amyloid plaques in the brain are associated with oxidative stress. Over time, oxidative damage is toxic to neurons and likely contributes to Alzheimer's disease. The brain's unique characteristics, including its high rate of metabolism and its long-living cells, make it susceptible to oxidative damage.
The Role of Antioxidants
Humans are equipped with a defense system that controls ROS and mends oxidative damage. This defense system is referred to collectively as the Antioxidant Defense System (ADS), and acts to regulate oxidative reactions.
The ADS includes enzymes and antioxidants to prevent the start of oxidative damage and/or control its spread. Antioxidants are either endogenous (made by the body) or exogenous (consumed).
Antioxidants block the process of oxidative stress by neutralizing free radicals. Antioxidant resources are depleted with age, so there is a constant need to replenish them. The effectiveness of any given antioxidant in the body depends on which free radical is involved, how and where it is generated and where the target of damage is.
Neurons are particularly vulnerable to oxidative stress due to their naturally low levels of antioxidants, the high content of fat in their membranes (free radicals love to attack fats), and their high requirement for energy. When oxygen is used to generate energy, the byproduct of energy production is the formation of free radicals.
Oxidative stress in neurons occurs primarily at the synapse (the space between the sending neuron and the receiving neuron). This is due to the high concentration of energy that occurs at synapses and the high concentration of mitochondria found there. Mitochondria are the power producing energy centers in cells. Generating energy produces unbalanced oxygen molecules which act as free radicals. These free radicals attack the neuron's protein, fat and DNA.
The image below illustrates the damage inflicted by free radicals to fats and proteins found in neurons.
Source: Alzheimer's Disease Unraveling the Mystery. US Department of Health and Human Services, National Institute of Health, NIH Publication Number: 02-3782, 2002;36.
References
- Keller, JN et al. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology. 2005; 64:1152-1156.
- Guidi I, et al. Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease. Neurobiology of Aging. 2006;27(2):262-269.
- Pawlak, L. A Perfect Ten. Biomed General Corporation, 1998. (107-109)