The document summarizes the history, chemical structure, biosynthesis, functions, disease treatments, efficacy data, recommended dosages, forms, and regulations of coenzyme Q10. It was first isolated in 1957 and its structure determined in 1958. It plays a key role in ATP synthesis as an antioxidant, and research shows benefits for heart disease, hypertension, and Parkinson's. Doses range from 30-100mg depending on the condition. It is considered a dietary supplement under DSHEA and cannot claim to treat or cure diseases.

1. THE AVENGER
Coenzyme Q10: Ubiquinone
BY
DR. ABDULRAB SHAIKH

2. History
 1957 - Coenzyme Q10 was first isolated from beef
heart mitochondria by Dr. Frederick Crane
 1958 - The precise chemical structure of
Coenzyme Q10 was determined by professor Karl
Folkers and collaborators at Merck, Inc.
 1961 - Coenzyme Q10 was considered as a
potential treatment for cancer.
 1964 – Coenzyme Q10 demonstrated its
usefulness for the treatment of congestive heart
failure.
 1970 – Coenzyme Q10 demonstrated its
effectiveness as an anti-oxidant.

4. Biosynthesis of Coenzyme Q
1. Synthesis of the benzoquinone structure from either tyrosine
or phenylalanine
2. Synthesis of the isoprene side chain from acetyl-
coenzyme A via the mevalonate pathway.
3. Condensation by the HMG-CoA reductase

5. Coenzyme Q10: Ubiquinone
 lipophilic, water-insoluble substances
 benzoquinone “head” and terpinoid “tail”
 various coenzymes Q relate to the number of isoprenoid units (5-carbon
structure) in the tail
 Can be one to 12 isoprenoid units
 10 isoprenoid units are the prevalent form in humans
 Solid-waxlike substance
 present in most tissues
§ The highest concentrations is found in the heart, the liver, the kidneys, and
the pancreas.
§ The lowest concentration is found in the lungs.

6. Oxidation States of Coenzyme Q10:
Ubiquinone
 Exists in three oxidation states.

7. Functions of Coenzyme Q10:
Mitochondrial ATP Synthesis
 transfer electrons from complex I or complex II  complex
III.
 initially is reduced to the semi-ubiquinone radical and then
ubiquinone by transfering electrons one at a time to complex
III
 At the same time, transfers the protons outside the inner
mitochondrial membrane, generates a proton gradient across
the membrane.
 The energy released when the protons flow back into the
mitochondrial interior is used to form ATP.
Plays an integral role in supplying energy to chemical reactions in the body

8. Functions of Coenzyme Q10:
Antioxidant
 neutralize free-radical
 an effective lipid-soluble antioxidant
 continuously go through an oxidation-reduction state
 hold electrons loosely in its reduced form
 regenerate α-tocopherol from the α-tocopheroxyl radical.
 interact with dihydrolipoic acid.
 Dihydrolipoic acid reduces ubiquinone to ubiquinol
 inhibit lipid peroxidation
 occurs when cell membranes and low-density lipoproteins (LDL)
are oxidized ex vivo
May prevent signs of skin aging

9. Functions of Coenzyme Q10:
Lysosomal Function
 transport protons across lysosomal
membranes
 help to maintain the optimal pH for
cellular recycling

10. Disease Treatment of Coenzyme
Q10: Ubiquinone
 Reliable and relatively consistent scientific data showing a substantial health benefit
for Angina and Hypertension
– Singh et. al. – double-blind, placebo-controlled study
 59 men already on hypertension medications had 120mg Coenzyme Q10 daily for 8 week
 Blood pressure reduced by about 9% as compared to placebo
– Burke et. al – double-blind, placebo-controlled study
 83 people with isolated systolic hypertension had 60mg Coenzyme Q10 daily for 12 week
 Blood pressure reduced
 Contradictory, insufficient, or preliminary studies suggesting a health benefit or
minimal health benefit for Cardiomyopathy, Cerebellar ataxia (familial), Congestive heart
failure, Diabetes, Gingivitis (periodontal disease), Halitosis (if gum disease), Migraine
headaches, Parkinson's disease, Renal (kidney) failure
– Baggio et al. – open marketing study
 2500 Class II or III patients had 100mg Coenzyme Q10 for 3 months with
 Signs of heart failure were reduced: 77% in edema, 54% in dyspnea, 82% in jugular venous pressure.
– Khatta et al. – double-blind, placebo-controlled study
 85 CHF patients had Coenzyme Q10 treatment
 Failed to find any evidence of benefit the patients with coenzyme Q treatment.
 For an herb, supported by traditional use but minimal or no scientific evidence. For a
supplement, little scientific support and/or minimal health benefit for Alzheimer’s
disease, Athletic performance, Breast cancer, Chronic obstructive pulmonary disease
(COPD), HIV support, Infertility (male), Insulin resistance syndrome (Syndrome X), Lung
cancer, Muscular dystrophy, Prostate cancer

11. Efficacy Data
 A lot of studies in the literature (70+)
– Laboratory/Animal/Preclinical studies
 Laboratory – Coenzyme’ structures and function in cell respiration
 Animal – pretreatment
– Human/Clinical studies
 Disease treatment
 For Heart disease:
– Some large trials (up to 360 patients)
– Some long term (up to 30 months)
– Double-blind placebo-controlled trial, or meta-analysis
 Others:
– Small trials (usually less than 100 people)
– Short term (up to 12 week)
– Most are double-blind randomized placebo-controlled trial
– Few are non-double blind, or non-randomized

12. Coenzyme Q10: Ubiquinone
 By definition not a vitamin
 Produced endogenously in all tissues (~0.5g/day
regenerated, with a body pool of ~2g)
Naturally present in small amounts in a wide varied of foods
Rich sources can be found in organ meats such as heart, liver and
kidney, as well as beef, soy oil, sardines, mackerel and peanuts
1 pound of sardines = 30 mg
2 pounds of beef = 30 mg
2.5 pounds of peanuts = 30 mg
50 times more antioxidant power than Vitamin E
Found to sustain vitamin E’s antioxidant effects

13. Coenzyme Q10: Ubiquinone
Endogenous synthesis decreases after age 20
Believed to fall off rapidly in middle age, accelerating the
aging process
Exercise increases catabolism of and need for CoQ10
Disease or other stress impairs intake and absorption of
the substrate

14. Drug Action of Coenzyme Q10:
Ubiquinone
Absorption
Absorbed in the small intestines directly into the lymphatic
system, followed by absorption into the blood stream
Absorption tends to be poor (lipophilicity)
~60% or more of oral dosage forms are excreted in the feces
Can be highly variable, depending upon dosage form and on food
intake at time of CoQ ingestion
Absorption is lower if taken on an empty stomach and higher if
taken with foods, especially those with a high lipid content

15. Drug Action of Coenzyme Q10:
Ubiquinone
Distribution/Metabolism
In the blood, CoQ10 is partitioned into various lipoproteins:
VLDL, LDL and HDL, with peak blood levels occurring in 5 to 10
hours
It is found in all cells of the body and is distributed to the various
tissues of the body (important to know that is able to enter the
brain)
Takes roughly 3 weeks of daily dosing to reach the maximum serum
concentrations
Excretion
Of what is absorbed elimination occurs through the bodies bile
Low plasma clearance
Elimination half-life of 34 hours

16. Dosage Forms of Coenzyme Q10:
Ubiquinone
 Capsules (10 mg, 30 mg, 75 mg, 100 mg, 150 mg)
 Chewable Tablets (100 mg, 200 mg)
 Liquid softgel (30 mg/5 ml)
 Tablets (25 mg, 50 mg, 60 mg, 200 mg)
 Wafers (60 mg, 200 mg)
 Vcaps (bio-grown CoQ10; 22mg)
 Can also be found in a number of skin products on the
market

17. Dosage Forms of Coenzyme Q10:
Ubiquinone
 CoEnzyme Q10, 300mg (60 caps): $84.96 WholeHealth.com
 Pure Encapsulated CoQ10 60mg (250caps): $132.00; 30mg
(250caps): $76.80 Graceful Earth.com
 Coenzyme Q-10 30 mg (60 chewable tabs): $9.09
 CoEnzyme Q10, 50 mg (200 Softgels): $44.18
 Co-Q-10-Plus, 50 mg (60 tabs): $41.50 Cybervitamins.com
 CoQ10 Vitaline, Enzymatic Therapy, 100 mg (30 Chocolate Flavored
Chewable Wafers): $25.88 iherb.com
 New Chapter Organics Bio-Grown CoQ10, 22mg (30 Vcaps): $23.24
drugstore.com
 Nivea Visage Q10 Advanced Wrinkle Reducer Lotion SPF 15: $10.99
drugstore.com
 Nivea Visage Q10 Advanced Wrinkle Reducer Night Crème: $10.99
drugstore.com
 Nivea Visage Q10 Advanced Wrinkle Reducer Plus Eye Creme SPF 4 0.5
oz (14 g): $10.99 drugstore.com

18. Recommended Dosage Amounts
for Coenzyme Q: Ubiquinone
 No known toxic dose
 For Hypertension: 30 mg, 2 times a day
 For Angina: 50 mg, 3 times a day
 For Congestive Heart Failure
Mild: 30 mg a day
Severe: 30 mg, 3 times a day
 For Cardiomyopathy: 50 mg, 2 times a day
 As an Antioxidant: 30 mg to 60 mg a day
 Mitral Valve Prolapse in Children: 2 mg/kg/day

19. Dietary Supplement Health and
Education Act of 1994
 The term "dietary supplement“ under Section 201 (21 U.S.C. 321)
(1) means a product (other than tobacco) intended to supplement the diet that
bears or contains one or more of the following dietary ingredients:
(A) a vitamin;
(B) a mineral;
(C) an herb or other botanical;
(D) an amino acid;
(E) a dietary substance for use by man to supplement the diet by increasing the
total dietary intake; or
(F) a concentrate, metabolite, constituent, extract, or combination of any ingredient
described in clause (A), (B), (C), (D), or (E);
(2) means a product that
(A)(i) is intended for ingestion in a form described in section 411(c)(1)(B)(i); or
(ii) complies with section 411(c)(1)(B)(ii);
(B) is not represented for use as a conventional food or as a sole item of a meal or
the diet; and
(C) is labeled as a dietary supplement; and

20. FDA: Laws and regulations
 No determined state regulations on this product
 Violations of the Dietary Supplement Health and Education
Act of 1994 (amendment to the Federal Food, Drug, and
Cosmetic Act) occur when claims are made that a supplement are
intended for the use in the diagnosis, cure, mitigation, treatment or
prevention of disease
 Why is this important?
 Because the above statement is the FDA’s definition of a drug
 And a new drug may not be legally marketed in the United States
without an approved New Drug Application (NDA)
T.J. Clark Liquid Co-Q10 Advanced Formula:
“[A] very beneficial supplement for individuals who suffer
from disorders of the cardiovascular system....“
“Revive failing hearts... Lower blood pressure”

21. References
 Anne Keogh, Steve Fenton, Christina Leslie, et. al. Randomised Double-Blind, Placebo-Controlled Trial of
Coenzyme Q10 Therapy in Class II and III Systolic Heart Failure. Heart Lung & Circulation. 2003;12:135-41.
 Baggio E, Gandini R, Plancher A, et. al. Italian multicentre study on the safety and efficacy of Coenzyme Q10 as
adjunctive therapy in heart failure. The Coenzyme Q10 Drug Survellance Investigators. Clin. Invest.
1993;71:S145-9.
 Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in
isolated systolic hypertension. South Med Journal. 2001;94:1112-7.
 Flint Beal, Clifford Shults. Effects of Coenzyme Q10 in Huntington’s disease and early Parkinson’s disease.
BioFactors 18. 2003;18:153-161.
 Franklin Rosenfield, Deborah Hilton, Salvatore Pepe, et. al. Systematic review of effect of coenzyme Q10 in
physical exercise, hypertension and heart failure. BioFactors. 2003;18:91-100.
 Kenneth Jones, Kerry Hughs, Laurie Mischley, et. al. Coenzyme Q-10 and Cardiovascular Health. Alternative
therapies. 2004;10(1):22-30.
 Langsjoen PH, Langsjoen PH, Folkers K. A six year clinical study of therapy
of cardiomyopathy with coenzyme Q10. Int J Tissue React(Swtizerland), 1990;12(3):169-71.
 Singh R, Niaz MA, Rastogi SS, et. al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin
resistance in hypertensive patients with coronary artery disease. J Human Hypertens. 1999:13:203-8.
 Ely, JTA and Krone, CA. A Brief Update on Ubiquinone (Coenzyme Q10). Journal of Orthomolecular Medicine
2000; 15(2):63-68. Retrived from the web on May 8, 2005 at http://faculty.washington.edu/~ely/JOM5.html
 Langsjoen, PH. Introduction to Coenzyme Q10. Retrieved from the web on May 8, 2005 at
http://faculty.washington.edu/~ely/coenzq10.html#FAQ
 Facts and Comparisons: The review of Natural Products. Aug 1997
 Physicians Desk Reference. 2005. Retrieved from the web on May 6, 2005 at
http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/coe_0084.shtml
 Micromedix. 2005. OSU subscription
 National Cancer Institute (NCI) and National Center for Complementary and Alternative Medicine (NCAM).
Retrieved from the web on May 8, 2005 at http://cis.nci.nih.gov/fact/9_16.htm
 Dietary Supplement Health and Education Act of 1994, Public Law 103-417, 103rd Congress. Retrieved from the
web on May 8, 2005 at http://www.fda.gov/opacom/laws/dshea.html
 Federal Food, Drug and Cosmetic Act, Title 21, Chapter 9. Retrieved from the web on May 8, 2005 at
http://www.access.gpo.gov/uscode/title21/chapter9_.html
 Walgreens.com
 Drugstore.com