L-Methyl-B6-B12 is a medical food for the clinical dietary management of the metabolic imbalances associated with hyperhomocysteinemia that cannot be managed by diet modification alone. Dispense by prescription. Use under medical supervision.

Hyperhomocysteinemia of any etiology.

Medical foods are intended for the patient who has a limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone1.

L-Methyl-B6-B12 is a specially formulated medical food for the dietary support of patients with hyperhomocysteinemia. It also is helpful in managing patients with high total homocysteine concentrations associated with malabsorption of vitamin B12 or suboptimal intake of B vitamins.

L-Methyl-B6-B12 Tablets should always be used under medical supervision.

Folic acid itself does not occur in nature; it is synthetic and lacks coenzyme activity. To be beneficial in human metabolism, orally administered folic acid must be absorbed through the brush border of the intestine and transferred to the liver where it is reduced to tetrahydrofolate (THF) form within the cell. L-5-methyl-tetrahydrofolate (5MTHF) is the predominant form of dietary folate and the only species normally found in the systemic circulation. Although 5MTHF does not occur in natural foodstuffs, it has been specially synthesized and formulated and is commercially available as the calcium salt.

5MTHF is at least as effective as folic acid in improving folate status as measured by blood concentration of folate and by functional indicators of folate status, such as plasma homocysteine. 5MTHF may have advantages over folic acid because it may reduce folate's potential for masking vitamin B12 deficiency; 5MTHF also may be associated with a reduced interaction with drugs that inhibit dihydrofolate reductase.2

Homocysteine (HCy) is an intermediary in amino acid metabolism. It is not a building block of protein itself, but is an integral part of methionine metabolism.3 Hyperhomocysteinemia (HHCy) is frequently associated with folate deficiency, and 5MTHF works in concert with vitamin B12 as a methyl-group donor in the remethylation of homocysteine to methionine.4,5 In this way 5MTHF can act to reduce the amount of serum homocysteine.4

HHCy has been associated with a myriad of medical conditions, including those concerning folate deficiency,5 endothelial dysfunction,6-10 oxidative stress of endothelial cells,11,12 vascular dysfunction,5,13 pre-eclampsia,14,15 coronary artery disease,6,8,13 microvascular angina,12 cardiovascular disease,7,16,17 wound healing,18 microvascular endothelium,19 and cerebral endothelium.20 Most of these reports include discussions of a nitric acid synthase (NOS) mechanism for the pathophysiology, in which HHCy impairs NOS function.5-8,10-20

HCy impairs the nitric oxide synthase pathway,17 and antagonizes Nitric Oxide (NO) production,12,16,18 and disrupts NO signaling.20 HCy promotes oxidative stress in endothelial cells via an NOS-dependent mechanism.11 Oxidative stress lowers the bioavailability of NO, presumably by impairing NOS.12,16 NO has been considered to be a mediator of the repair of oxidative stress damage.18 In particular, the endothelial cells of the cardiovascular and central nervous system tissues rely on NO for wound repair, and endothelium and microvascular integrity12,18. When NOS activity is impaired by HCy, both a lack and an excess of NO can have important pathological implications.16

In one study, 5-MTHF had beneficial effects on endothelial function and decreased vascular superoxide production by improving NOS "coupling."10

5-MTHF uniquely counteracts the harmful effects of HHCy and provides nutritional support for patients who have medical conditions related to oxidative stress and impaired activity of inducible or endothelial NOS.

Vitamin B6 plays an active role in the maintenance of normal HCy levels.21

Vitamin B12 is a cofactor in the conversion of homocysteine to methionine (which in turn is required for the synthesis of S-adenosylmethionine, a universal methyl donor).22,23

Active and ongoing medical supervision is required for the clinical management of patients with HHCy.

L-METHYL-B6∙B12 is contraindicated in patients with known hypersensitivity to any of the components contained in this product.

Discontinue use if patient exhibits signs of hypersensitivity such as tachycardia, urticaria, or shortness of breath.

Folic acid, when administered in daily doses above 0.1 mg, may obscure the detection of vitamin B12 deficiency, including pernicious anemia. L-METHYL-B6-B12 may be less likely than folic acid to mask vitamin B12 deficiency.2

The recommended dose is one tablet twice daily or as directed. L-Methyl-B6-B12 tablets must be used under medical supervision.

L-Methyl-B6-B12 is available as a round coated purple colored tablet, debossed with "V362" on one side and blank on the other. Commercial product is supplied in bottles of ninety (90) tablets.

NDC 42291-359-90

Some or all of the following patents may apply:

U.S. Patent No. 4,940,658
U.S. Patent No. 5,563,126
U.S. Patent No. 5,795,873
U.S. Patent No. 5,997,915
U.S. Patent No. 6,011,040
U.S. Patent No. 6,207,651
U.S. Patent No. 6,254,904
U.S. Patent No. 6,297,224
U.S. Patent No. 6,528,496
and other pending patent applications.

1

United States Food and Drug Administration Title 21 Code of Federal Regulations 101.90(j)(8).

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He L, Zeng H, Feng J, et al. Am J Physiol Endocrinol Metab (2010) Dec 299(6): E1061-1065.

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20

Antoniades C, Shirodaria C, Warrick N, et al. 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels. Effects on Vascular Tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation (2006) 114: 1193-1201.

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Manufactured for:
AvKARE, Inc.
Pulaski, TN 38478

Mfg. Rev. 10/15 
AV 07/16 (P)

AvKARE

NDC 42291-359-90

L-Methyl-B6-B12

Tablets

Medical Food

90 Tablets        Rx

Description:
Each round coated purple colored tablet contains:
Pyridoxal-5'-Phosphate ...................... 35 mg
L-methylfolate Calcium ......................... 3 mg
Methylcobalamin .................................. 2 mg

DOSAGE AND ADMINISTRATION: The recommended dose is one tablet twice daily (B.I.D.) or as directed by a licensed medical practitioner.

STORAGE: Store at controlled room temperature 15° to 30°C (59° to 86°F).

Ingredients:
Dibasic Calcium Phosphate Dihydrate, Microcrystalline Cellulose 90, Pyridoxal-5'-Phosphate, Microcrystalline Cellulose HD 90, Opadry II Purple 40L10045 (Polydextrose, Titanium Dioxide, Hypromellose 3cP, Hypromellose 6cP, Glycerol Triacetate, Hypromellose 50cP, FD&C Blue #2, FD&C Red #40 and Polyglycol 8000), Microcrystalline Cellulose 50, Opadry II Clear Y-19-7483 (Hypromellose 6cP, Maltodextrin, Hypromellose 3cP, Polyglycol 400, Hypromellose 50cP),
L-methylfolate Calcium, Magnesium Stearate, Methylcobalamin, and Carnauba Wax.

Contains FD&C Blue #2 and FD&C Red #40.

USE: L-METHYL-B6-B12 Tablets is a medical food dispensed by prescription for the clinical dietary management of hyperhomocysteinemia.

Use under medical supervision.

This product has been manufactured in a facility that also manufactures products containing milk and soy. Individuals with allergic tendencies to these substances should use discretion.

Protect from light and moisture.

Dispense in a tight, light-resistant container.

If you are pregnant or nursing a baby, ask a health professional.

KEEP THIS OUT OF REACH OF CHILDREN.