PoDiaPN is an orally administered medical food* for patients with metabolic nutritional impairments associated with peripheral neuropathy and microvascular complications.
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.
(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.
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.
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.
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.
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.
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.
Each capsule contains:
(6S)-5- methyltetrahydrofolic acid, glucosamine salt)
|Pyridoxal 5'-phosphate [Coenzyme B6]
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.
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*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