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.
3.
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
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
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