About

PoDiaPN Stands Alone Among Comparable Medical Foods

Medical Food* for Patients with Metabolic Nutritional Impairments Associated with Peripheral Neuropathy and Microvascular Complications

Featuring Quatrefolic®, the (6S)-5-MTHF Glucosamine Salt Form of Folate, and Alpha-Lipoic Acid with Pyridoxal 5'-Phosphate and Methylcobalamin

Why Is (6S)-5-MTHF Better Than Folic Acid and (6S)-5-MTHF Calcium Salt?

  • Not likely to mask B12 deficiency
  • Effectively lowers homocysteine[1]
  • Seven times more bioavailable than folic acid[2]
  • The active form of folate naturally present in the body
  • Preferred form, especially for those with disturbances in folate metabolism
  • Not affected by the MTHFR C677T polymorphism
  • Improved bioavailability over folic acid and (6S)-5-MTHF calcium salt
  • 100 times more water soluble than (6S)-5-MTHF calcium salt

Why Include Alpha-Lipoic Acid (ALA)?

  • ALA is a multifunctional antioxidant that affects the oxidant and inflammatory pathways associated with microvascular complications.
  • ALA has been licensed in Germany for symptomatic neuropathy for 40 years.
  • In six human clinical studies, alphalipoic acid was administered orally to approximately 400 patients at doses equivalent to those found in PoDiaPN. Results of these studies indicated that an oral dose of 600 mg/d was well tolerated and provided significant benefits.

*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.

What is a Medical Food?

A medical food, 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."

As defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)).


What is peripheral neuropathy (PN)?

"An estimated 20 million people in the United States have some form of peripheral neuropathy, a condition that develops as a result of damage to the peripheral nervous system — the vast communications network that transmits information between the central nervous system (the brain and spinal cord) and every other part of the body. (Neuropathy means nerve disease or damage.) Symptoms can range from numbness or tingling, to pricking sensations (paresthesia), or muscle weakness. Areas of the body may become abnormally sensitive leading to an exaggeratedly intense or distorted experience of touch (allodynia). In such cases, pain may occur in response to a stimulus that does not normally provoke pain. Severe symptoms may include burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. Damage to nerves that supply internal organs may impair digestion, sweating, sexual function, and urination. In the most extreme cases, breathing may become difficult, or organ failure may occur. "

Diseases or disorders that can be associated with peripheral neuropathy include:

  • Metabolic and endocrine disorders, such as Diabetes (the leading cause of PN in the United States)
  • Small vessel disease
  • Autoimmune diseases
  • Kidney disorders
  • Cancers
  • Neuromas
  • Infections

Peripheral Neuropathy Fact Sheet.(n.d.). In National Institute of Neurological Disorders and Stroke.Retrieved from http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm.

The Research

 

Research suggests that the underlying pathology of peripheral neuropathy (PN) involves a complex interaction between metabolic and vascular factors that converges on nerves and the endothelium of the peripheral microvasculature. Patients can present with loss of protective sensation, neuropathic pain, and, in some cases, lower extremity ulcerations.

PoDiaPN is designed to address these factors by providing targeted actives at clinically effective levels to address oxidant and inflammatory pathways as well as hyperhomocysteinemia and endothelial dysfunction. Each of these conditions can contribute to decreased nitric oxide production and, eventually, nerve damage.

Use of PoDiaPN should always occur under the care of a physician.

Quatrefolic Versus Folic Acid and (6S)-5-MTHF Calcium Salt

Preclinical Study

This test was a direct comparison between Quatrefolic, (6S)-5-MTHF calcium salt, and folic acid in rats. It showed the difference in bioavailability in vivo between the three folate generations

5-MTHF Plasma Levels in Rats After Oral Administration of Different Folates

Used with permission from Gnosis S.p.A.

Improved Bioavailability

(6S)-5-methyltetrahydrofolate hematic peak produced by an equivalent dose of the indicated folate source.

Used with permission from Gnosis S.p.A.

In a single-dose, balanced, two-sequence, two-period, two-treatment, randomized, crossover human study, Quatrefolic showed better bioavailability (+10%) than (6S)-5-MTHF calcium salt (Ca-L-5- MTHF).

Pharmacokinetic Study

  Quatrefolic® Ca-L-5-MTHF  
Pharmacokinetic parameter Mean SD CV% Mean SD CV% D%
Cmax (nmol/L) 94.55 21.98 23.2 85.29 28.46 33.4 10.9
AUC (nmol/L.h) 549.2 142.68 26.0 501.1 151.1 30.2 9.6
  1. Venn BJ, et al. Am J Clin Nutr. 2003 Mar;77(3):658-62. [PMID: 12600857]
  2. Willems FF, et al. Br J Pharmacol. 2004 Mar;141(5):825-30. [PMID: 14769778]

Used with permission from Gnosis S.p.A.

PoDiaPN

Clinically Effective Levels of:

  •   Bioactive Folate, Quatrefolic®
  •   Alpha-Lipoic Acid
  •   Pyridoxal 5'-Phosphate
  •   Methylcobalamin
PoDiaPN

 

 

Enjoy Getting Back into Circulation!

 

PoDiaPN® Information

DESCRIPTION

PoDiaPN is an orally administered medical food* for patients with metabolic nutritional impairments associated with peripheral neuropathy and microvascular complications.

ADMINISTRATION

PoDiaPN is to be administered orally, one capsule twice daily. Capsules are intended to be swallowed whole with water. Use of PoDiaPN should always occur under the care of a physician.

PHARMACOLOGY

(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. Research has shown (6S)-5-MTHF to be seven times more bioavailable than folic acid.

Therapeutically, (6S)-5-MTHF is used to reduce homocysteine levels and to improve vascular endothelial function through its influence on nitric oxide (NO). Clinical studies have shown that direct supplementation with (6S)-5-MTHF reduces homocysteine levels and increases plasma folate levels more effectively than folic acid.

In fact, folic acid supplementation alone was shown not to reduce intracellular homocysteine. Inborn genetic variations (polymorphisms) in the MTHFR gene are the most common genetic causes for elevated homocysteine levels.

(6S)-5-MTHF glucosamine salt (Quatrefolic®) is a new dietary ingredient (NDI) that shows enhanced stability and bioavailability when compared to the (6S)-5-MTHF calcium salt form.

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).

Methylcobalamin is a vitamin B12 analog that is neurologically active and is necessary for nervous system function. Methylcobalamin's neuroprotective effects may be mediated by the methylation cycle. In conjunction with supplemented folate, the addition of Vitamin B12 has been shown to reduce homocysteine more than folic acid alone. Clinical trials suggest the combination of [6S]-5-MTHF, P5P and methylcobalamin can reduce symptoms of neuropathy.

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. Elevated levels of homocysteine (hyperhomocysteinemia, HHcy) is associated with peripheral neuropathy and is considered an independent risk factor for the development of PN. 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. 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 redox couple effects of ALA/DHLA 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.

INDICATIONS AND USAGE
PoDiaPN capsules are indicated for the specific dietary requirements of patients with hyperhomocysteinemia and/or endothelial dysfunction associated with peripheral neuropathy.

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 lower extremity neuropathic pain, loss of protective sensation, or, in some cases, ulceration.

PoDiaPN should always be used under medical supervision.

CONTRAINDICATIONS

PoDiaPN is contraindicated in children, pregnant or nursing women, women of childbearing age who may become pregnant, and anyone with a known hypersensitivity to any of the components.

ALA is contraindicated in individuals who are thiamine deficient.

PRECAUTIONS

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. (6S)-5-MTHF is unlikely to mask B12 deficiency.

ADVERSE REACTIONS
Patients taking a combination of B vitamins at levels that are comparable to those found in PoDiaPN have reported numbness in two fingers, dizziness, and balance disorder. Folic acid supplementation has been reported to cause gastrointestinal (GI) distress, irritability, excitability, sleep disturbances, and allergic reactions in some individuals. Human trials using 0.4 to 17 mg/day of (6S)-5-MTHF showed an absence of adverse effects. Paresthesia, somnolence, 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. 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.

This is not a comprehensive list of adverse reactions, others may occur. Consult a current, comprehensive database for all potential adverse reactions.

DRUG INTERACTIONS

Folic acid could decrease the effectiveness of methotrexate, pyrimethamine, and anti-seizure medications/first-generation anticonvulsants (phenytoin, carbamazepine, valproate, fosphenytoin, phenobarbital, primidone, for example). 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 may exacerbate photosensitivity caused by amiodarone. Pyridoxal 5'-phosphate [B6] may also affect metabolism and may therefore decrease the effectiveness of levodopa, phenobarbital, and phenytoin.

Pyridoxal 5'-phosphate [B6] should not be given to patients receiving the drug levodopa, because the action of levodopa is antagonized by Pyridoxal 5'-phosphate [B6]. However, Pyridoxal 5'-phosphate [B6] may be used concurrently in patients receiving a preparation containing both carbidopa and levodopa.

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

This is not a complete list of drug interactions.

Talk to your doctor or pharmacist before using any other prescription or over-the- counter medicines or herbal/health supplements with PoDiaPN.

STORAGE: Store at 20° to 25° C (68° to 77° F), the controlled room temperature defined by the U.S. Pharmacopeia (USP).

HOW SUPPLIED: PoDiaPN green opaque capsules are supplied in a bottle of 60 count 53731-002-06 and in a sample size package of two 53731-002-99.

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

DESCRIPTION
Each capsule contains:

Quatrefolic®
(6S)-5- methyltetrahydrofolic acid, glucosamine salt)
5 mg
Pyridoxal 5'-phosphate [Coenzyme B6] 35 mg
Methylcobalamin 2 mg

Complete Ingredient Listing: Alpha-lipoic acid, capsule (hydroxypropyl methylcellulose, titanium dioxide, sodium copper chlorophyllin) pyridoxal 5'-phosphate, vegetable stearic acid, vegetable magnesium stearate, silica, Quatrefolic® ((6S)-5-methyltetrahydrofolic acid, glucosamine salt), microcrystalline cellulose, and methylcobalamin.

PoDiaPN capsules do not contain sugar, lactose, yeast or gluten.

DISTRIBUTED BY:
PharmaceutiX
6900 Kingspointe Pkwy
Orlando, FL 32819
800-647-6100

*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.

REFERENCES AVAILABLE UPON REQUEST


PoDiaPN® Capsules
PoDiaPN Capsules

REV. 101215

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