PoDiaPN® Vegetarian Capsules
53731-0002-06†

PoDiaPN is an orally administered medical food* for patients with distinctive nutritional requirements related to diabetic peripheral neuropathy and its vascular complications.

PoDiaPN is to be administered orally, one capsule twice daily with or without food. Capsules are intended to be swallowed whole with water. Use of PoDiaPN should always occur under the supervision of a physician.

(6S)-5-methyltetrahydrofolic acid ([6S]-5-MTHF) is the primary biologically active isomer of folate. Unlike supplementary folic acid, which requires enzymatic reduction by the methylenetetrahydrofolate reductase enzyme (MTHFR) to become biologically active, (6S)-5-MTHF is able to penetrate cellular membranes without requiring metabolism.¹ Research has shown (6S)-5-MTHF is nearly seven times more bioavailable than folic acid.²

Therapeutically, (6S)-5-MTHF is used to assist in the reduction of elevated homocysteine levels³ and to improve vascular endothelial function through its influence on nitric oxide (NO).⁴ Clinical studies have shown that direct supplementation with (6S)-5-MTHF reduces homocysteine levels and increases plasma folate levels more effectively than folic acid.⁵ Inborn genetic variations (polymorphisms) in the MTHFR gene are an acknowledged cause of elevated homocysteine blood levels.³

(6S)-5-MTHF glucosamine salt (Quatrefolic®) shows enhanced stability and bioavailability when compared to the (6S)-5-MTHF calcium salt form.⁶

Pyridoxal 5'-phosphate (P5P) is the metabolically active coenzyme form of vitamin B₆. P5P-dependent enzymes are involved in many biochemical reactions, including the transsulfuration of homocysteine and decarboxylation of amino acids that yield biogenic amines (neurotransmitters).⁷

Methylcobalamin is a vitamin B₁₂ analog that is neurologically active and is necessary for nervous system function. It is important for the production of myelin, the protective covering surrounding nerves.⁸ Methylcobalamin’s neuroprotective effects may be mediated by the methylation cycle.^9,10 Clinical trials suggest the combination of (6S)-5-MTHF, P5P, and methylcobalamin can reduce symptoms of neuropathy.^11,12

METABOLIC AND VASCULAR HYPOXIC FACTORS IN PERIPHERAL NEUROPATHY (PN)
Research suggests that the underlying pathology of PN involves a complex interaction between metabolic and vascular factors that converges on nerves and the endothelium of the peripheral microvasculature.^13-15

An elevated level of homocysteine (hyperhomocysteinemia, HHcy) is associated with peripheral neuropathy and is considered an independent risk factor for the development of PN. Homocysteine can have a direct toxic effect on nerves, or it can cause neurovascular dysfunction.¹⁶ HHcy inhibits endothelium-mediated nitric-oxide–dependent vasodilation and is thought to contribute to endothelial dysfunction (ED). ED is complex, involving multiple mechanisms, not the least of which are HHcy, oxidative stress, and the resulting reduced bioavailability of nitric oxide (NO). With respect to peripheral nerves, insufficient NO causes vasoconstriction and therefore reduced blood flow to peripheral nerves. Reduced blood flow translates into the inadequate transfer of nutrients to peripheral nerve cells and consequent nerve damage. Alternately, studies suggest that enhancing endothelial function and reversing some of these factors that interfere with NO production will increase NO, improve blood flow through vasodilation, enable the delivery of essential nutrients and oxygen to peripheral nerves, and thereby allow the nerves to perform normal functions.^17-19 PoDiaPN is designed to address metabolic and vascular processes, such as those discussed above that are disrupted in patients with microvascular complications.

OTHER INGREDIENTS
Alpha-lipoic acid (ALA) is a multifunctional antioxidant that is orally absorbed and converted to its reduced form (dihydrolipoic acid or DHLA) in many tissues. The effects of the ALA/DHLA redux couple are important in biological processes, including the regulation of gene expression and the modulation of enzyme and receptor activities; these mechanisms have important implications relating to oxidative stress and inflammatory pathways.²⁰

INDICATIONS AND USAGE
PoDiaPN capsules are indicated for patients with distinctive nutritional requirements related to diabetic peripheral neuropathy and its vascular complications.

PoDiaPN capsules are also indicated for the metabolic nutritional impairments of patients with chronic inflammation or oxidative stress associated with microvascular complications. These patients typically present with hyperhomocysteinemia, endothelial dysfunction, lower extremity neuropathic pain, loss of protective sensation, or, in some cases, ulceration.

PoDiaPN should always be used under the supervision of a physician.

PoDiaPN is contraindicated in anyone with a known prior hypersensitivity to its ingredients. Children, pregnant or nursing women, and women of childbearing age should consult with their practitioner prior to use. ALA is contraindicated in individuals who are thiamine deficient, such as people who are dependent on alcohol.

Patients taking agents that lower blood pressure, affect blood sugar levels, or increase bleeding risk should be monitored. High-dose folic acid intake without concurrent B₁₂ supplementation may mask the symptoms of pernicious, aplastic, or normocytic anemias caused by vitamin B₁₂ deficiency. Compared to folic acid, (6S)-5-MTHF is less likely to mask a vitamin B₁₂ deficiency.²¹

ADVERSE REACTIONS
Folic acid supplementation has been reported to cause gastrointestinal (GI) distress, irritability, excitability, sleep disturbances, and allergic reactions in some individuals. Human trials using 680 mcg DFE to 28,900 mcg DFE/d of (6S)-5-MTHF showed an absence of adverse effects. Burning, prickling skin, sleepiness, nausea, and headaches have been reported with pyridoxal 5'-phosphate (coenzyme form of vitamin B₆). Doses of B₆ under 200 mg/d are not likely to cause adverse effects unless an individual is particularly sensitive. Neurological and GI disturbances and skin reactions have been reported. Excessive doses may cause reversible sensory neuropathy.^22,23

Vitamin B₁₂ may cause GI disturbances, polycythemia vera, or allergic reactions in sensitive individuals. ALA may cause mild skin rash, GI complaints, or dizziness; these are primarily associated with doses over 1200 mg/d.^22,23

Folic acid could decrease the effectiveness of methotrexate, pyrimethamine, and anti-seizure medications/first-generation anticonvulsants (phenytoin, carbamazepine, valproate, fosphenytoin, phenobarbital, primidone, for example).²³ It is not known if (6S)-5-MTHF has the same interactions, so caution is recommended when prescribing PoDiaPN among patients who are taking these medications. Vitamin B₆ (found in PoDiaPN aspyridoxyl 5'-phosphate) may decrease the effectiveness of levodopa, phenobarbital, and phenytoin by increasing the metabolism of these drugs. Vitamin B₆ should not be given to patients receiving levodopa; however, it may be used by patients receiving a combination of levodopa with carbidopa (e.g., Sinemet). Vitamin B₆ may reduce the therapeutic effectiveness of altretamine. In doses higher than the 70 mg/d of vitamin B₆ in the recommended dose of PoDiaPN, (e.g., 200 mg/d), the vitamin may increase the metabolism of barbiturates.²³

Vitamin B₁₂ should not be combined with chloramphenicol.²³ Alpha-lipoic acid may interact with thyroid medications.²⁴ Theoretically, concomitant use of alpha-lipoic acid with antidiabetic drugs may have an additive effect.²⁵

This is not a complete list of drug interactions. Before using this product, inform your physician or pharmacist of all the products you use. Keep a list of all of your medications with you, and share the list with your physician and pharmacist.

Reference list available upon request

STORAGE Store at 20° to 25°C (68° to 77°F). Protect from heat, light, and moisture.

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

INGREDIENTS: Alpha-lipoic acid, capsule (HPMC, titanium dioxide, sodium copper chlorophyllin), pyridoxal 5'-phosphate, vegetable stearic acid, vegetable magnesium stearate, silica, (6S)-5-methyltetrahydrofolic acid glucosamine salt,^S1 microcrystalline cellulose, and methylcobalamin.

FORMULATED TO EXCLUDE: Wheat, gluten, corn, yeast, soy, animal and dairy products, fish, shellfish, peanuts, tree nuts, egg, ingredients derived from genetically modified organisms (GMOs), artificial sweeteners, and artificial preservatives.

PharmaceutiX®
6900 Kingspointe Pkwy
Orlando, FL 32819
800-647-6100
info@pharmaceutixhealth.com

S1. Quatrefolic® is a registered trademark of Gnosis S.p.A. Produced under U.S. patent 7,947,662.

*Official FDA information about medical foods can be found in 21 U.S.C. sec. 360ee(b) (3), 21 C.F.R. sec. 101.9 (j) (8), and "Guidance for Industry: Frequently Asked Questions About Medical Foods" (May 2007), FDA website.

Quatrefolic® is a registered trademark of Gnosis S.p.A. Produced under US Patent 7,947,662.

C.A.S.# 1181972-37-1

*A medical food, as defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)), is "a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation."

†PharmaceutiX® does not represent these product codes to be National Drug Codes (NDC). Product codes are formatted according to standard industry practice to meet the formatting requirements of pharmacy and health insurance computer systems.

PoDiaPN® Vegetarian Capsules
(60 Count)

REV. 050721