Description:   PROXEED is a dietary supplement specifically formulated to optimize sperm quality. Sperm quality refers to motility, rapid linear progression, count, concentration and morphology.*

Suggested Use:   To optimize sperm quality.*

Active Ingredients:   L-carnitine fumarate, fructose, acetyl-L-carnitine HCl, citric acid.

Levocarnitine (L-carnitine) is a carrier molecule for medium- and long-chain fatty acids and is essential in the transportation of these fatty acids into the mitochondria where they can be utilized for (beta)-oxidation. Levocarnitine is a component of both seminal plasma and sperm cells, and it plays a critical role in sperm maturation and potential sperm motility. ^1-3 *

Fructose is one of the major energy-yielding substrates present in seminal fluid. ⁴ *

Acetyl-L-carnitine is the acetyl ester of levocarnitine and occurs naturally in the body. When converted to acetyl-CoA, it can enter the Krebs Cycle, be converted to acetoacetate (a ketone body) or be used for fatty acid synthesis. Additionally, acetyl-L-carnitine is important for membrane stabilization, is the most prominent form of carnitine in sperm, ^5-7 serves as a circulating energy source for sperm, ^5-7 plays an important role in sperm maturation and metabolism ^5-7 and provides the primary fuel for sperm motility. ^{4-5, 8} *

Citric acid is a key intermediate in the Kreb's Cycle.*

Inactive Ingredients:   mannitol, polyethylene glycol, artificial flavorings, povidone, silicon dioxide.

Clinical Findings*:   Among healthy couples taking longer than expected to conceive, poor sperm quality is a contributing factor for nearly 40% of all cases. ⁵ PROXEED'S primary ingredients are levocarnitine and acetyl-L-carnitine. In 12 clinical trials, levocarnitine and acetyl-L-carnitine have been proven to provide the nutritional support needed for sperm' production of energy and optimum sperm quality. ^{2-3, 5, 8-16}

Supplementation with the ingredients in PROXEED significantly improved percent motile sperm. ^{2, 3, 8-16}

Mean (± SD) percent motile sperm was normalized after 3 months of supplementation with L-carnitine. ² [p-not reported]*

Mean (± SEM) percent rapid linear progression showed a greater than 60% improvement after 4 months of supplementation with L-carnitine. ⁸ [p>0.001]*

Mean (±SEM) sperm count increased 14.7% after 4 months of supplementation with L-carnitine. ⁸ [p <0.001]*

Sperm concentration also improved after 3-4 months of supplement-ation. ^{2, 8, 10, 12, 16}

There has been only limited data on whether the ingredients in PROXEED have a measurable effect on sperm morphology.

Bioavailability/Pharmacokinetics:* Levocarnitine and acetyl-L-carnitine have bioavailabilities of between 5 and 15% in healthy adults. Clinical studies have shown that oral doses of 3 g per day (total) of carnitines are appropriate to optimize sperm quality. ^{2, 8, 12, 16} To achieve the appropriate dose, it is necessary for PROXEED to be provided as a powder formulation.

The oral half-lives of L-carnitine and acetyl-L-carnitine are approximately 3-4 hours. As a result, the total daily dose should be divided b.i.d., and spaced 8 or more hours apart to maintain elevated blood levels of L-carnitine and acetyl-L-carnitine.

Precautions:   As with all supplements, please keep this product out of the reach of children, and consult with your physician before use if you are taking any medications.

Contraindications:   None known.

Drug Interactions:   None known.

Dosage & Administration:   For Adult Males: Take two packets of PROXEED per day, one packet in the morning and one packet in the evening. Mix each packet with at least 4 ounces (120 ml) of juice or other beverage. Initial results should be seen within 3 months and continued improvement-leading to optimum results-within 6 months.* Patients who miss a dose should continue with the next dose. Double dosing is not necessary.

PROXEED is designed for long-term administration and should be taken for as long as attempting to conceive.*

On average, sperm require 74 days to mature, and up to 30 additional days to become capable of fertilization. Initial results should be seen within 3 months and continued improvement-leading to optimum results-within 6 months.

How Supplied:   PROXEED is available in single dose packets packaged 30 per box. PROXEED's powder formulation allows for the necessary ingredients in the amounts shown to be effective in clinical trials.

To order PROXEED, visit the web site,

www.proxeed.com or call toll-free,

(877) PROXEED (776-9333).

PROXEED is manufactured for Sigma-Tau Pharmaceuticals, Inc., Gaithersburg, Maryland 20877. Product of Italy. PROXEED™ is a trademark of Sigma-Tau HealthScience S.p.A. U.S. Patent #5,863,940. All rights reserved.

References :

1. Jeulin, C, et al , Role of Free L-carnitine and Acetyl-L-carnitine in Post-Gonadal Maturation of Mammalian Spermatozoa. Human Reproduction Update 1996; 2(2): 87-102
2. Vitali, G, et al , Carnitine Supplementation in Human Idiopathic Asthenospermia: Clinical Results. Drugs Experimental Clinical Research 1995; 21(4): 157-159
3. Loumbakis, P, et al , Effect of L-carnitine in Patients with Asthenospermia; 12th Congress of the European Association of Urology, Sept. 1-4, 1996. Paris in European Urology 1996; 30(2): 225, Abstract 954
4. Golan, R, et al , Influence of Various Substrates on the Acetylcarnitine: Carnitine Ratio in Motile and Immotile Human Spermatozoa. Reproduction and Fertility 1986; 78: 287-293
5. Moncada, ML, et al , Effect of Acetylcarnitine Treatment in Oligoasthenospermic Patients. Acta Europaea Fertilitatis 1992; 23(5): 221-224
6. Bartellini, M, et al , L-carnitine and Acetylcarnitine in Human Sperm with Normal and Reduced Motility. Acta Europaea Fertilitatis 1987; 19(1): 29-31
7. Kohengkul, S, et al , Levels of L-carnitine and L-0-acetylcarnitine in Normal and Infertile Human Semen: A Lower Level of L-0-acetylcarnitine in Infertile Semen. Fertility and Sterility 1977; 28(12): 1333-1336
8. Costa, M, et al , L-carnitine in Idiopathic Asthenozoospermia: A Multicenter Study. Andrologia 1994; 26: 155-159
9. Campaniello, E, et al , Carnitine Administration in Asthenospermia; 4th International Congress of Andrology, Firenze, May 14-18, 1989. Abstract
10. Muller-Tyl, E, et al , Effects of Carnitine on Sperm Count and Motility. Fertilitat 1988; 4(1): 1-4
11. Micic, S, et al , Does L-carnitine Administered In Vivo Improve Sperm Motility? ARTA 1995; 7: 127-130
12. Micic, S, Effects of L-carnitine on Sperm Motility and Number in Infertile Men; 16th World Congress on Fertility and Sterility, San Francisco, Oct. 4-9, 1998. Abstract
13. Vicari, E, Effectiveness of Short-Term Anti-Oxidant High-Dose Therapy of IVF Program Outcome in Infertile Male Patients with Previous Excessive Antimicrobials Administered for Epididymitis: Preliminary Results. Infertility and Assisted Reproductive Technology: From Research to Therapy, Ambrosini, A, et al, Monduzzi Editore, Bologna, 1997; 93-97
14. Vicari, E, et al, Effectiveness of Single and Combined Antioxidant Therapy in Patients with Asthenonecrozoospermia from Non-Bacterial Epididymitis: Effects after Acetyl-L-carnitine or Levocarnitine. Italian Andrology Association, 12 ^th National Conference, Copanello (CZ), June 9-12, 1999. Abstract
15. Vicari, E, et al, Production of Oxygen Free Radicals in Varicocele: Pre- and Post-Treatment Evaluation and Observations after Pharmacological Trial. Italian Andrology Association, 12 ^th National Conference, Copanello (CZ), June 9-12, 1999. Abstract
16. Micic, S, et al, Carnitine Therapy of Oligospermic Men. 25 ^th Annual Meeting of the American Society of Andrology. Boston, 2000. Abstract

pxd-papi-4 ©2000 Sigma-Tau Consumer Products 9/00

Sigma-Tau Consumer Products
a division of Sigma-Tau
Pharmaceuticals, Inc.
Gaithersburg, Maryland 20877

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