Zymes llc. CoQ10 and Neurodegenerative Disease

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CoQ₁₀ and Neurodegenerative Disease

The nervous system is comprised of the Central Nervous System (CNS), which includes the brain and spinal cord, and the Peripheral Nervous System (PNS) which connects the CNS to other parts of the body. The functional unit of the nervous system is the nerve cell, or neuron. Neurons communicate with each other using neurotransmitters, chemical “messengers” which transmit signals from one cell to another. The nervous system has three basic functions: 1) receive sensory input from internal and external environments 2) integrate the input and 3) respond to the input.

Sensory input exists in many forms, including pressure, taste, sound, light, blood pH, or hormone levels, which are converted into a signal and sent to the brain or spinal cord. In the sensory centers of the brain or spinal cord, input is integrated and a response is generated. The response, a motor output, converts the signal into some form of action such as movement, changes in heart rate, release of hormones, etc. The classic example is touching a hot stove. Heat is the sensory input that is converted into a signal transmitted to the CNS. The motor output generates the response to quickly remove your hand.

Neurodegenerative diseases affect brain function and result from deterioration and loss of neurons in the CNS. Changes in these nerve cells cause them to function abnormally, eventually bringing about their death. Neurodegenerative diseases are divided into two groups:

Conditions causing problems with movements (Parkinson’s disease, Huntington’s disease)
Conditions affecting memory or relating to dementia (Alzheimer’s disease)

There is a growing body of evidence to suggest that oxidative stress and damage to mitochondria play a role in neurodegenerative diseases. Oxidative stress is caused by cellular accumulation of reactive oxygen species (ROS) which are potentially harmful chemicals produced during normal metabolic processes and in response to various stimuli. These ROS, found primarily in the mitochondria, are “quenched” by antioxidants and converted into non-toxic compounds. However, accumulation of these species in tissues can result in cell dysfunction and death. This may result from excessive production of ROS, decreased antioxidants, or both. Excessive cell death is a common characteristic of neurodegenerative diseases and stroke.

Evidence of oxidative stress such as oxidized lipids, DNA, and proteins have been found in patients with Alzheimer’s disease, ¹ Huntington’s disease, ² Parkinson’s disease ³ and amyotrophic lateral sclerosis (ALS).⁴ Decreased levels of antioxidant producing enzymes are found in patients with Parkinson’s disease. Some researchers have suggested that Alzheimer’s may be linked to diets low in antioxidants.⁶
Coenzyme Q₁₀ is thought to play a beneficial role in neurodegenerative diseases due to both its antioxidant effects and its beneficial role in maintaining healthy mitochondria. Blood levels of Coenzyme Q₁₀ are lower in patients with Parkinson’s disease compared to age-matched controls. ⁷ Some researchers have found that blood levels of Coenzyme Q₁₀ are normal in patients with Alzheimer’s ⁸ and Parkinson’s disease. ^{9, 10} However, it has been suggested that it is more important to measure the level of coenzyme Q₁₀ in the cells, and mitochondria of cells, than in the blood. To support this notion, the amount of coenzyme Q₁₀ available to act as an antioxidant was found to be reduced in the platelets and in the mitochondria ¹² of patients with Parkinson’s disease. ¹¹

Parkinson’s Disease

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease. It affects about 1 in every 100 persons over age 50. This brain disease is characterized by four major features:

Resting tremor of a limb (shaking when the limb is at rest)
Slowness of movement
Rigidity (stiffness, increased resistance to movement) of the limbs or trunk
Poor balance

When at least two of these symptoms are present, especially if they are more evident on one side than the other, a diagnosis of Parkinson’s disease is made.

Parkinson’s Disease is a progressive disease that results when nerve cells in a part of the brain, called the substantia nigra, are impaired or die. These nerve cells produce dopamine, an important neurotransmitter that conveys signals from the substantia nigra to another part of the brain called the corpus striatum. These signals facilitate coordinated movement. When the dopamine-secreting cells in the substantia nigra die, there is a breakdown in communication between neurons and the movement control centers in the brain become unregulated. Disturbances in the movement control centers of the brain cause the symptoms of PD, which develop when 80% of the dopamine-producing cells in the substantia nigra are depleted.

Although the causes of Parkinson’s disease are not well known, increased oxidative stress in the substantia nigra and decreased activity of the mitochondrial electron transport chain are thought to play a key role. Oxidative stress results in the production of substances (such as free radicals or reactive oxygen species) that may be harmful to cells and lead to their deaths. Cell loss in the substantia nigra is the cause of symptoms of Parkinson’s disease.

Coenzyme Q₁₀ is an essential component of the electron transport chain, and is required for its function. It is also a potent antioxidant able to prevent oxidative damage caused by free radicals . Levels of coenzyme Q₁₀ have been found to be decreased in blood and in platelet mitochondria of individuals with Parkinson’s disease. ^{11, 12} Experimental models of Parkinson’s disease have further shown that coenzyme Q₁₀can protect the dopamine secreting cells of the substantia nigra. This prompted investigators to examine the potential role of coenzyme Q₁₀in the prevention and treatment of Parkinson’s disease and other neurodegenerative diseases.

In 2002 Shults and coworkers studied the safety and efficacy of coenzyme Q₁₀ to slow the progression of Parkinson disease in the first multicenter, randomized, placebo-controlled, double-blind trial. Eighty patients with early Parkinson disease were treated with either placebo or coenzyme Q₁₀ at dosages of 300, 600, or 1200 mg per day and followed for 16 months or until their disability required treatment with levodopa. The study showed that less disability developed in patients taking coenzyme Q₁₀ than in those taking the placebo. The benefit was greatest in patients taking the highest doses of coenzyme Q₁₀. There was also a dose dependent increase in blood levels of coenzyme Q₁₀. These promising preliminary findings need to be confirmed in larger clinical trials. ¹³

A 16-month randomized, placebo-controlled trial evaluated the safety and efficacy of 300, 600, or 1200 mg/d of coenzyme Q₁₀ in 80 people with early Parkinson’s disease. ¹³ Coenzyme Q₁₀ supplementation was well tolerated at all doses and associated with slower deterioration of function in Parkinson’s disease patients compared to patients taking placebo. However, the difference was statistically significant only in the group taking 1200 mg/d. Although these preliminary findings are promising, they need to be confirmed in larger clinical trials before recommending the use of coenzyme Q₁₀ in early Parkinson’s disease.

To prepare for a larger clinical study of higher doses of coenzyme Q₁₀, the safety of doses greater than 1200 mg/day was evaluated in 17 patients with Parkinson’s disease in an open label study. ¹⁴ The patients received increasing doses of coenzyme Q₁₀ from 1200 to 3000 mg/day. Thirteen of the 17 patients reached the highest dose of 3000 mg/day. No adverse events were attributed to coenzyme Q₁₀. Blood levels of coenzyme Q₁₀ reached a plateau with the 2400 mg/day establishing this as the suggested dosage for future studies of Parkinson’s disease with coenzyme Q₁₀. ¹⁵

Alzheimer’s Disease

Alzheimer’s is a neurodegenerative disease and the most common cause of dementia. The most striking early symptom is short term memory loss, which usually manifests as minor forgetfulness which becomes more pronounced over time. There is relative preservation of long term memory. As Alzheimer’s progresses, intellectual impairment extends to the domains of language (aphasia), skilled movements (apraxia), recognition (agnosia), and functions such as decision-making and planning. The underlying disease is characterized by loss of nerve cells together with inflammation caused by protein deposits (amyloid plaques and neurofibrillary tangles) in tissues of the brain. The ultimate cause of the disease is unknown. Genetic factors are known to be important, and mutations in three different genes have been identified that account for a small number of cases of familial, early-onset Alzheimer’s Disease. For late onset Alzheimer’s Disease, only one susceptibility gene has been identified to date.

Knowledge of the role of coenzyme Q₁₀ in patients with Alzheimer’s disease is not as broad as it is for Parkinson’s disease. However, advances are being made with in vitro (in test tubes) experiments and animal models of this disease.

Proteins fold in specific ways to enable them to perform their biochemical functions in the body. In Alzheimer’s disease some proteins fold improperly, forming deposits of non-functional proteins in the brain known beta-amyloid fibrils. Decreasing the formation of beta-amyloid fibrils or disrupting already formed beta-amyloid fibrils would be a potential way to treat patients with Alzheimer’s disease. In vitro experiments showed that coenzyme Q₁₀ was able to decrease the formation of beta-amyloid fibrils and disrupt already formed beta-amyloid fibrils. ¹⁶

Bragin and co-workers studied the effect of the combination of multivitamins, vitamin E, alpha-lipoic acid, omega-3 fatty acids and coenzyme Q₁₀ on cognition in 35 ill patients about 71 years of age who were diagnosed with mild dementia and depression. The combination of multivitamins, vitamin E, alpha-lipoic acid, omega-3 fatty acids and coenzyme Q₁₀ slowed the decline in and even improved cognition. ¹⁷

Rats trained to run through a maze can be treated with a chemical called streptozotocin that causes them to lose their memory of the maze. This loss of memory is associated with oxidative damage to the brain. Memory loss and oxidative damage to the brain are also characteristics of Alzheimer’s dementia. When rats were treated with streptozotocin and then supplemented with coenzyme Q₁₀, the memory loss and oxidative damage improved, suggesting that coenzyme Q₁₀ may be effective in patients with Alzheimer’s dementia. ¹⁸

Huntington’s Disease

Huntington’s disease, formerly known as Huntington’s chorea, is a rare, fatal, inherited neurodegenerative disorder in which there is degeneration of specific nerve cells known as striatal spiny neurons. The symptoms, such as movement disorders and impaired cognitive function, generally develop between 40 and 50 years of life and deteriorate with time.

The Huntington Study Group conducted a multicenter, parallel group, double-blind, randomized study of 347 patients with early Huntington’s disease to evaluate the effects of coenzyme Q₁₀ (300 mg twice a day), remacemide 200 mg three times a day, or both for 30 months. Neither treatment significantly slowed the decline in total functional capacity. However, there was a trend toward a reduction in the decline of total functional capacity of 13% in patients treated with coenzyme Q₁₀. ¹⁹ Studies of coenzyme Q₁₀ in patients with Parkinson’s disease suggest that higher doses may be required to provide a demonstrable clinical benefit. ¹³

Koroshetz et al. studied a measure of brain metabolic health, lactate concentrations (using MRI), in patients with Huntington’s disease and compared it with healthy control subjects. Brain lactate concentrations were increased in patients with Huntington’s disease compared to controls. Lactate concentration decreased with coenzyme Q₁₀ treatment and increased again upon discontinuation of coenzyme Q₁₀ treatment - suggesting a possible benefit of this antioxidant in Huntington’s disease. ²⁰

Andrich and colleagues compared blood levels of coenzyme Q₁₀ in patients with Huntington’s disease who were untreated and treated, and compared them to healthy controls. There was no difference between blood levels of coenzyme Q₁₀ in treated patients with Huntington’s disease and healthy controls. However, blood levels of coenzyme Q₁₀ were significantly lower in untreated patients compared to those that were treated and compared to healthy controls. ²¹

Feigin et al. conducted a 6-month open-label study of coenzyme Q₁₀ in 10 patients with Huntington’s disease. There was no significant effect of coenzyme Q₁₀ on the clinical ratings of Huntington’s disease Rating Scale, the Huntington’s disease Functional Capacity Scale (HDFCS), or the standardized neuropsychological measures. ²²

On the other hand, several studies evaluating the effect of coenzyme Q₁₀ in animal models of Huntington’s disease have shown promising results. ^23-29

Learn more about ongoing studies of coenzyme Q₁₀.

References:

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Sohmiya M, Tanaka M, Tak NW, Yanagisawa M, Tanino Y, Suzuki Y, Okamoto K, Yamamoto Y. Redox status of plasma coenzyme Q₁₀ indicates elevated systemic oxidative stress in Parkinson’s disease. J Neurol Sci. 2004 Aug 30;223(2):161-6.
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Matsubara et al. Serum coenzyme Q₁₀ level in Parkinson syndrome. In: Folkers K, Littaru GP, Yamagami eds. Biochemical and Clinical Aspects of Coenzyme Q1. New York, NY Elsevier Science Publishers; 1991:159-166.
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Shults CW, Haas RH, Passov D, Beal MF. Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol. 1997;42(2):261-264.
Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group. Effects of coenzyme Q₁₀ in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002;59(10):1541-1550.
Shults CW, Flint Beal M, Song D, Fontaine D. Pilot trial of high dosages of coenzyme Q₁₀ in patients with Parkinson’s disease. Exp Neurol. 2004;188(2):491-494.
Ogawa O, Zhu X, Perry G, Smith MA. Mitochondrial abnormalities and oxidative imbalance in neurodegenerative disease. Sci Aging Knowledge Environ. 2002;2002(41):pe16.
Ono K, Hasegawa K, Naiki H, Yamada M. Preformed beta-amyloid fibrils are destabilized by coenzyme Q10 in vitro. Biochem Biophys Res Commun. 2005;330(1):111-6.
Bragin V, Chemodanova M, Dzhafarova N, Bragin I, Czerniawski JL, Aliev G. Integrated treatment approach improves cognitive function in demented and clinically depressed patients. Am J Alzheimers Dis Other Demen. 2005;20(1):21-6.
Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, Ahmad AS, Islam F. Coenzyme Q₁₀modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behav Brain Res. 2006;171(1):9-16.
Huntington Study Group. A randomized, placebo-controlled trial of coenzyme Q₁₀ and remacemide in Huntington’s disease. Neurology. 2001;57(3):397-404.
Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF. Energy metabolism defects in Huntington’s disease and effects of coenzyme Q10. Ann Neurol. 1997;41(2):160-5.
Andrich J, Saft C, Gerlach M, Schneider B, Arz A, Kuhn W, Muller T. Coenzyme Q₁₀ serum levels in Huntington’s disease. J Neural Transm Suppl. 2004;(68):111-6.
Feigin A, Kieburtz K, Como P, Hickey C, Claude K, Abwender D, Zimmerman C, Steinberg K, Shoulson I. Assessment of coenzyme Q₁₀ tolerability in Huntington’s disease. Mov Disord. 1996;11(3):321-3.
Beal MF. Coenzyme Q₁₀ as a possible treatment for neurodegenerative diseases. Free Radic Res. 2002;36(4):455-60.
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Kasparova S, Sumbalova Z, Bystricky P, Kucharska J, Liptaj T, Mlynarik V, Gvozdjakova A. Effect of coenzyme Q₁₀ and vitamin E on brain energy metabolism in the animal model of Huntington’s disease. Neurochem Int. 2006;48(2):93-9.
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Smith KM, Matson S, Matson WR, Cormier K, Del Signore SJ, Hagerty SW, Stack EC, Ryu H, Ferrante RJ. Dose ranging and efficacy study of high-dose coenzyme Q₍₁₀₎ formulations in Huntington’s disease mice. Biochim Biophys Acta. 2006 Jun;1762(6):616-26.
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Page modified: 2007-04-19 16:49:34.

Adipose - Fat tissue.

Aerobic - Without oxygen.

Adequate Intake (AI) - A recommended intake value based on observed or experimentally determined approximations or estimates of nutrient intake by a group (or groups) of healthy people, that are assumed to be adequate- used when an RDA cannot be determined.

Aldosterone - A steroid hormone, synthesized from cholesterol by the adrenal gland regulates sodium and potassium levels in the blood.

Amyloid Plaques - An abnormal accumulation of beta-amyloid proteins in the brain that are seen in patients with Alzheimer’s disease.

Amino Acids - Small molecules that are the building blocks of proteins.

Analogue - Something that is similar to something else.

Antioxidant - A chemical compound or substance like a vitamin that inhibits the oxidation of other molecules.

Arteries - Blood vessels that carry oxygenated blood away from the heart, whereas veins carry deoxygenated blood to the heart.

Atherosclerosis - A disease of the arteries resulting from the formation of an atherosclerosis plaque, historically known as “hardening of the arteries”. The plaque consists of excess cholesterol and other lipids, inflammatory cells such as macrophages, with excess of proteins and calcium. The plaque eventually ruptures and causes narrowing of the artery leading to an insufficient blood supply to the organ it feeds.

ATP - Adenosine triphosphate. The cells of the body cannot use food directly for energy. The energy (calories) in food must be broken down into a form of energy small enough for the cells to use. That smallest form of energy is ATP.

Bias - To influence in an unfair way.

Beta Blocker - A medicine used to treat high blood pressure and some other heart conditions.

Bile Acids - Specific compounds produced by the liver and excreted in the bile to help in the digestion of fats.

Bioavailability - A term used by pharmacologists and pharmacists to describe the amount of a medication that reaches the blood stream.

Biological Membranes - All cells are surrounded by a cell membrane, sometimes called a plasma membrane or plasmalemma. It is a thin double layer of phospholipid and proteins that envelopes the cell, separating the cell’s interior from its surroundings and controlling what moves in and out.

Biosynthesis - A process where chemical compounds are made in the body from simpler compounds or smaller molecules, an important part of metabolism.

Blinded - Most clinical studies are “blinded” to assure accurate results. Double-blinded means that neither the patient nor the investigator know which group the patient is assigned to. Single-blinded means the investigator knows which group the patient is assigned to, but the patient does not.

Carbohydrates - Commonly known as sugars (monosaccharides and disaccharides) and starches (polysaccharides), their most important function is energy storage.

Cardiac Asthma - An asthmatic attack caused by heart disease.

Cell Membrane - Also called a plasma membrane or plasmalemma. It is the outermost layer of a cell composed of primarily phospholipids and proteins. It serves to separate and protect the cell interior from its surroundings and regulate the movement of molecules into and out of cell.

Centers for Disease Control (CDC) - A government agency that studies infectious diseases.

Chemical Bonds - The holding together of molecules by attraction of atoms to each other, commonly through sharing of electrons.

Chylomicrons - Small fat globule composed of protein and lipid (fat) created by the cells of the small intestine used to transport fat from the intestine to the liver and to fat tissue. After a fatty meal, the blood is so full of chylomicrons that it looks milky.

Cognition - The ability to think, reason, and remember.

Confidence Intervals - Describes the range within which the real effect is likely to occur. As with the 5% chance described for the p value, the confidence interval usually provided is the 95% confidence interval. For example if a new cholesterol drug lowered cholesterol by a mean of 20 mg/dL with a 95% CI of 4 to 35, there is a 95% probability that the true effect of the drug lies within this range. If the CI does not overlap 1.0, the result is said to be significant at p<0.05. In our example the CI (4, 35) does not overlap 1.0, therefore the treatment effect is considered to be statistically significant.

Cortisol - A steroid hormone, synthesized from cholesterol by the adrenal gland that is involved in the response to stress. Also used as a drug, synthetic cortisol also known as hydrocortisone, is used to teat allergic and inflammatory diseases.

Dementia - A progressive decline in mental functioning, over and above what’s expected from normal aging, due to damage or disease in the brain.

Double Blind - In clinical studies, double blind means that neither the patient nor the investigator know which treatment group the patient is assigned to.

Dietary Reference Intakes - Includes four measurements; Recommended Daily Allowance (RDA), Allowable Intake (AI), Tolerable Upper Intake Level (UL) and Estimated Average Requirement (EAR). DRI is generally used by nutrition professionals instead of RDAs.

Efficacy - The ability of a drug to produce an acceptable amount of the desired effect. In precise terms ‘efficacy’ refers to the effect of a drug in the controlled setting of a clinical trial. This is different from ‘effectiveness’ which refers to the effect of a drug in real world setting.

Electron - A negatively charged particle that orbits the nucleus of an atom. The flow of electrons produces electricity.

Electron Transport Chain - The energy currency of the body, ATP, is made in the mitochondria, from the food we eat, through a series of chemical reactions called the electron transport chain. Electrons are transported through a series of compounds in what is known as the electron transport chain. Each time electrons are transferred from one compound to another, the energy generates a proton gradient that provides the energy to produce ATP.

Eliminate - After drugs are metabolized, they are removes from the body by two main routes: in the urine through the kidneys and in the feces through the gastrointestinal tract.

Enterocyte - An intestinal cell that helps to break up food molecules and transports them into the tissues of the body.

Estimated Average Requirement (EAR) - A daily nutrient intake value that is estimated to meet the requirement of half of the healthy individuals in a life stage and gender group - used to assess dietary adequacy and as the basis for RDA.

Estrogen - A steroid hormone, synthesized from cholesterol that is the primary hormone involved in the development of female sex characteristics. Estrogen is also present at a significantly lower level in men.

Fermentation - A process that occurs in the absence of oxygen such as making alcohol (wine) from grapes with yeast.

Fibrate - A class of drugs used to lower cholesterol that work differently than the statins.

Folic Acid - One of the B vitamins.

Free Radicals - Atoms or molecules with highly reactive unpaired electrons that are generally pro-oxidants. Also referred to as reactive oxygen species such as superoxide, hydrogen peroxide, and hydroxyl radical and are associated with cell damage. Free radicals are neutralized in the body by anti-oxidants.

Free Radical Scavenger - Found in every living cell of the body and are potent antioxidants.

Gamma Rays - Electromagnetic radiation of high energy that is released by radioactive decay.

Genetic Material - Deoxyribonucleic acid (DNA), used to store the genetic information of an organism.

Glucose Toxicity - High blood glucose can lead to damage of organs and the complications of diabetes.

Gram - The standard measure of mass in the metric system indicated by the symbol g. 1 gram (g) = 1000 milligrams (mg). 1 gram = 1/1000 of a kilogram (kg). 1 ounce = 28.3 grams, 1 gram is about the mass of a paper clip.

GRAS - Generally Regarded As Safe is recognition by the FDA (Food and Drug Administration of the Department of Health and Human Services) of the safety of a substance that is added to food.

Heavy Metals - Common metals that are “heavy” include gold, cobalt, copper, manganese, molybdenum, vanadium, strontium, zinc, mercury, lead, and cadmium. Some like cobalt, copper, manganese, molybdenum, vanadium, strontium, zinc, are required in the diet in trace amounts, but high levels can be detrimental. Others such as mercury, lead, and cadmium are not essential to bodily functions and accumulation is associated with illness.

Hemoglobin A1C (HbA1C) - A measure of blood sugar control over 2 to 3 months.

High Energy Phosphates - Compounds like adenosine triphosphate (ATP) and adenosine diphosphate (ADP) that contain high energy phosphate bonds that when broken release energy for the body to use.

HMG-CoA Reductase - The rate-limiting enzyme, 3 - hydroxy - 3 - methyl - glutaryl - CoA reductase or HMGR, of the pathway that synthesizes cholesterol and other molecules. Drugs that inhibit HMG-CoA reductase are commonly called statins because of the commonality of the generic drug names: atorvastatin, pravastatin, and simvastatin. Statins are used to lower blood levels of LDL cholesterol, a risk factor for cardiovascular disease.

Hormone - From the Greek horman - “to set in motion”. A chemical substance that is secreted into body fluids and transported to another cell or organ, where it produces a specific effect.

Hypothesis - The explanation for certain facts or observations that can be tested through experimentation.

Ionizing Radiation - Produced by radioactive decay, nuclear reactions, and by extremely hot objects like the sun. X-rays are a use of ionizing radiation as is radiation to kill cancerous cells. However, overuse of ionizing radiation can be hazardous.

In Vitro - Refers to experiments performed in test tubes or cell cultures.

In Vivo - Refers to experiments performed in live animals.

Jugular Reflux - An elevation of venous pressure that can be seen in bulging jugular veins and in the veins of the arm and can be produced by congestive heart failure.

LDL - Low density lipoprotein, a fatty droplet composed of protein and cholesterol used to carry cholesterol throughout the body. Referred to as the “bad” cholesterol because it may accumulate on the walls of the arteries leading to atherosclerosis.

Left Ventricle - The largest lower chamber of the heart, it that receives oxygenated blood from the left atrium and pumps it out to the body through the aorta to the body.

Lymphatic System - A network of vessels carrying lymph (a colorless fluid) to and from lymph organs (lymph nodes, spleen, and thymus) that produce and store infection-fighting cells.

Lymphoma - Any of the many often malignant tumors of the lymph nodes or in other lymphoid tissue.

Lactate/Pyruvate Ratio - Elevation in this ratio may be used to estimate mitochondrial dysfunction. If the mitochondria (makes energy through aerobic pathways) are not functioning properly, the body may turn to anerobic pathways to generate energy which increase lactate compare to pyruvate.

Lipases - Enzymes in the digestive system that break down fats.

Lipids - A class of water insoluble compounds essential for the structure and function of living cells. Lipids make up cell membranes and are used for energy storage. They also can be hormones and vitamins. Lipids are often called ‘fats’, however, fats are only one type of lipid.

Metabolism - All of the processes of the body including those that build up (anabolism) and breakdown (catabolism) molecules in the body. Drug metabolism is the process the body uses to break down (deactivate) a drug for elimination form the body.

Mevalonic Acid - A compound used by the body to make cholesterol and other steroids.

Mitochondria - A cell structure often referred to as the “powerhouse of the cell” because that is where the food we eat is turned into energy. All cells, with the exception of red blood cells, have mitochondria. Mitochondria convert the energy found in the food we eat into a small energy rich molecule called ATP that all cells can use.

Mitochondrial Electron Transport Chain - The energy currency of the body, ATP, is made in the mitochondria, from the food we eat, through a series of chemical reactions called the electron transport chain. Electrons are transported through a series of compounds in what is known as the electron transport chain. Each time electrons are transferred from one compound to another, the energy generates a proton gradient that provides the energy to produce ATP.

Multicenter - In clinical studies, when the same study is performed in patient found in more than one study center.

Myeloma - A tumor of antibody-producing cells that are normally found in the bone marrow.

Neurodegenerative Diseases - Disease that results from the deterioration of nerve cells such as Alzheimer’s disease and Parkinson’s disease.

Neuron - The nerve cells which make up the central nervous system that communicate to each other by transmitting electrical signals to other neurons.

Neutrons - A subatomic particle found in the nucleus of every atom, except hydrogen, it has no electrical charge; it is neutral.

Nucleic Acids - Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), the molecules the body uses to store and transmit genetic information.

Open Label - In clinical studies, when the patient knows which drug treatment they are being given.

Oxidative Phosphorylation - The process during which nutrients are broken down into ATP using the oxygen we breathe.

Oxidative Stress - A term for damage to animal or plant cells, tissues and organs caused by free radicals and other pro-oxidant molecules. It is often defined as an imbalance between too many pro-oxidants and not enough antioxidants.

Oxidized - Oxidation is the loss of an electron. Molecules that have the ability to oxidize other molecules are also known as pro-oxidants, oxidizing agents, oxidants or oxidizers. When the oxidant removes electrons from the other molecule, it becomes reduced.

Ozone - A molecule of three oxygen atoms present in low concentrations throughout the Earth’s atmosphere. In the upper atmosphere it prevents harmful ultraviolet light form reaching the Earth’s surface. At ground level ozone is associated with respiratory problems, atherosclerosis and Alzheimer’s disease.

Pancreas - An organ located near the stomach that makes digestive enzymes that aid in digestion, and it produces several hormones, including insulin and glucagon.

Pantothenic Acid - Also called vitamin B5, is an antioxidant water-soluble vitamin needed to break down carbohydrates, proteins, and fats.

pH - A measurement of acidity or alkalinity of a solution like blood or water.

Placebo-Controlled - Refers to a clinical trial in which the effectiveness of an experimental drug is compared to that of placebo (contains no useful medicinal content) group.

Platelet - Cells involved in blood clotting.

Progesterone - a steroid hormone, synthesized from cholesterol, involved in the regulation of the processes of the female reproductive system.

Pro-Oxidant - A substance that can produce oxygen byproducts of metabolism that can cause damage to cells.

Prospective - A study that collects data after the study begins; unlike a retrospective study which analyzes data that has already been collected.

Proteins - Chains of amino acids used by the body for many things including: cell movement (muscles), structures (hair), enzymes (biological catalysts), hormones (insulin), energy storage (egg albumin), transport of oxygen (hemoglobin), and antibodies (immune system).

PTS™ - The lead compound in the family of Ubisol-Aqua™ solubilizers.

Pulmonary Edema - Swelling and/or fluid accumulation in the lungs.

P Value - A measure of significance. A p value that is deemed significant if it is p<0.05 (read, p is less than .05). If the p value is less than 0.05, the difference between the treatment groups is considered statistically significant. It means that there is less than a 5% chance that the difference between the two treatment groups occurred by chance and that the difference between the two groups is most likely attributable to a treatment effect rather than chance. If the p value is greater than .05 (p>0.05), then it is likely that the difference between the two treatment groups occurred by chance.

Randomized - A method of assignment in which individuals have a random chance of being assigned to one group or another.

Range- Describes the highest and lowest number in the data set.

Reactive Oxygen Species - Atoms or molecules with highly reactive unpaired electrons that are generally pro-oxidants. Also referred to as free radicals and are associated with cell damage. Free radicals are neutralized in the body by anti-oxidants.

Recommended Daily Allowance - The average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group. RDA is now incorporated into the DRI. For more information please refer to the International Food Information Council.

Reduced - Reduction is the gaining of an electron. Molecules that have the ability to reduce other molecules are also known as reducing agents, reductants or reducers. When the reducing agent gains electrons from the other molecule, it becomes oxidized.

Remacemide - A drug used treat Parkinson’s disease.

Reperfusion Injury - The damage to tissue that is caused when the blood supply returns to the tissue after a period of no or reduced blood flow.

Safety - Relates to the detection, evaluation, understanding, and prevention of adverse effects of drugs during short and long term use.

Statistically Significant - A mathematical measure to describe if there is a difference between groups. The difference is said to be “statistically significant” if it is greater than what might be expected to happen by chance alone.

Striatal Spiny Neurons - A type of medium sized neuron in the striatum that when destroyed, may cause problems with movement.

Standard Deviation (SD) and Standard Error (SE) - Mathematically complex calculations. What you need to know is that large SD and SE indicate a lot of variability in the data, and small SD and SE indicate that the data values are clustered closely around the mean.

Statin - A group of drugs that reduce the amount of cholesterol made by the body.

Substantia Nigra - Dark gray matter deep within the brain where cells make the neurotransmitter dopamine for movement control. Degeneration of cells in this region may lead to movement disorders such as Parkinson’s disease.

Subcutaneous - Under the skin.

Synthetic - A substance that is made a chemical process, it generally does not apply to substances created by naturally occurring biological processes.

Testosterone - A steroid hormone, synthesized from cholesterol that is the primary hormone involved in the development of male sex characteristics. Testosterone is also present at a significantly lower level in women.

Tolerable Upper Intake Level (UL) - The highest level of daily nutrient intake that is likely to pose no risk of adverse health effects for almost all individuals in the general population. As intake increased above the UL, the potential risk of adverse effects increases.

Ultraviolet Light - Electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays.

United States Recommended Daily Allowances (USRDA) - Was devised by the Food and Drug Administration (FDA) for nutritional labeling of processed foods and vitamin products. The USRDA lists the percentage of each of 19 essential nutrients that are contained per serving of the labeled product. The Recommended Dietary Allowance (RDA) is the amount of nutrients and calories recommended for most healthy individuals (of any age) to consume in their daily diet to meet the requirements of the body.

Unsaturated Fats - A fat with one or more double bond in the fatty acid chain and liquid at room temperature. Unsaturated fats are commonly found in avocados, nuts, soybeans, canola oil and olive oil. Saturated fats have no double bonds in the fatty acid chain and are solid at room temperature such as butter and animal fat.

Ubiquinol - The reduced form of coenzyme Q₁₀.

Ubiquinone - The oxidized form of coenzyme Q₁₀.

Villus> - Hair-like protrusions into the intestine — emanating from the wall of the intestine. The purpose of the villi is to slow the passage of food, and to allow food particles to be captured in among these finger-like villi — so that the blood inside the villi can absorb the nutrients in the food.

Vitamin - A molecule required by the body in minute amounts for proper health. In general, vitamins cannot be made by the body.

X-Rays - A form of electromagnetic radiation primarily used in medicine to produce radiographic images. Is also a form of ionizing radiation which can be dangerous.