What is Folplex?

What is Folplex?

Folplex is a generic brand name included in the multivitamins and supplements category which has been used for the treatment of nutritional deficiency. It contains active ingredients including vitamin B12 (or cyanocobalamin - 0.5 mg), vitamin B6 (or pyridoxine - 25 mg) and Folic acid (or vitamin B9 - 2.2 mg) and inactive additives such as dibasic calcium phosphate, microcrystalline cellulose, modified cellulose gum, crospovidone, magnesium stearate, hypromellose, titanium dioxide, polydextrose, triacetin, polyethylene glycol, iron oxide red, and iron oxide yellow. Folplex replenishes the levels of vitamin B6, vitamin B9 and vitamin B12, and this combination of vitamins is available in multiple generic medications like Folgard, Foltx, Homocysteine Formula, etc. Folplex tablets (manufactured by Breckenridge Pharmaceuticals) oval-shaped, peach-colored tablets imprinted with B 352 on the scored side and plain on the other side. It is available in bottles of 100 tablets.

Folplex is used for maintenance of good health and growth, replenishment of deficient vitamins such as vitamin B6, vitamin B9 and vitamin B12, and for the treatment of hyperhomocysteinemia. Besides this, it has been used for the treatment of an inherited disease marked by the excretion of sulfur in the urine. Folplex is an oral dosage form that is usually taken with or without food once daily or as directed by a physician. The dosage is based on the medical condition and the response needed for persons with a deficiency of vitamin B6, vitamin B9 (folate) and vitamin B12. If the patient has a known allergy to any of the components of Folplex, or has an eye problem named Leber’s optic atrophy or if the patient is on levodopa administration, then Folplex should be used cautiously and strictly under the guidance of a physician.

Although most of the persons using Folplex do not face serious side effects, it could still have a few unwanted effects similar to that of allergic reactions like rashes, hives, itching, swollen or blistered skin with or without fever, tightness in the chest, difficulty in breathing or swallowing, etc. Some other lesser observed side effects include diarrhea, stomach upset, dizziness, headache and numbness/tingling sensation. If a dose is missed then it should be taken as soon as possible but it shouldn’t be close to the time of the next dose, which may lead to overdosing. Folplex should not be used along with certain medications like altretamine, cisplatin and levodopa (when used without carbidopa), methotrexate, phenytoin, etc. because of possible serious interactions. Therefore, the physician must be informed about any other medications used by the patient. It is not advisable in pediatric patients, as safety and efficacy have not been established in children. It must be stored in a dry place, at room temperature (15-30°C) protected from moisture and light in a tight container.

Folic acid, referred to as vitamin M or vitamin B9, is required for the synthesis of purines, pyrimidines and methionine inside the body. Vitamin B9 exists in two well-known forms, folic acid which is a man-made synthetic oxidized form and folate which is a reduced form. It acts as an essential cofactor for enzymes involved in the synthesis of DNA and RNA. The most bioavailable active form of folate is L-5-Methyltetrahydrofolate (or methylfolate) which needs no enzymatic conversion to take place within the body before the cells can use it directly. This is the most ideal form of folate to take, especially if you have trouble with folate metabolism, have an MTHFR genetic mutation or are seeking the most fundamental solution to a folate deficiency issue. 

Folate is particularly important during rapid cell division in infants, pregnant women, and erythropoiesis (the production of red blood cells). The food sources of folate are green leafy vegetables, sprouts, brewer’s yeast, beans, peanuts, sunflower seeds, cruciferous vegetables, fruits, whole grains, liver, seafood, egg, folic acid-containing supplements. As humans are unable to synthesize folic acid endogenously, fortified foods and folic acid supplementation have become necessary to prevent folate deficiency. Inadequate folate levels can result in several health concerns like cardiovascular disease, megaloblastic anemia, cognitive disorder, and neural tube defects (NTD). Therefore, folate is typically supplemented during pregnancy to prevent the development of NTD and in individuals with alcoholism to prevent the development of neurological disorders. High doses of folic acid supplements can lead to significant issues including masking vitamin B12 deficiency, increasing the risk of colorectal cancer and generating a large amount of unmetabolized folic acid in the plasma and urine (which make one more prone to cancers). Consuming high doses of synthetic folic acid supplements may salvage the hematological symptoms in some; however, the damage to the nervous system by the deficiency of vitamin B12 would likely be increased further. Thus, vitamin B12 deficiency masked by folic acid supplementation results in dysfunction of the nervous system including the brain and spinal cord.

One reason why folic acid supplementation is so controversial and confusing as to whether it actually helps or hinders an individual is because of the huge portion of the population that has folate metabolism genetic defects. MTHFR is a genetic variant responsible for converting the folate we eat into the form of folate our bodies will actually use for synthesis of important downstream processes like, fetal development, cardiovascular health, neurotransmitter production and balance, detoxification and so much more. The more preferred form of folate being suggested as a viable supplementation option ALONG WITH an active B12 supplement to prevent deficiency is L-Methylfolate. This form does not need to be converted by the MTHFR gene (which more than half of the population suffer from), but it can be immediately used by the body to do all of those fundamental tasks we require to keep our health on track (and to keep cancer at bay). So look for a product containingL-Methylfolate before going with a folic acid supplement if you need to boost your folate levels for optimal health - it’s much safer, even if it costs more.

Pyridoxine or vitamin B6, an important water-soluble vitamin that is essential for the normal execution of many biological functions within the body. It helps in the metabolism of protein, fat and carbohydrates, together with the synthesis of red blood cells. Vitamin B6 plays a key role in cognitive development via the biosynthesis of neurotransmitters. Vitamin B6 is the collective term for a group of six related compounds, pyridoxine, pyridoxal, and pyridoxamine, and their respective phosphorylated derivatives, pyridoxine 5'-phosphate, pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate. While many plants and microorganisms can synthesize pyridoxine through endogenous biological processes, animals must obtain it through their diet.

The food sources of vitamin B6 include potatoes and starchy vegetables, fish, beef liver and other organ meats, and fruits. Pyridoxine is converted to pyridoxal 5-phosphate in the body, which is an important coenzyme and involved in the synthesis of amino acids, neurotransmitters (serotonin, dopamine, norepinephrine and gamma-aminobutyric acid), sphingolipids, hemoglobin and nucleic acids. It is required for the brain development and immune functioning of the fetus during pregnancy. The deficiency of vitamin B6 causes peripheral neuropathy, pellagra, seborrheic dermatitis, glossitis and cheilosis. It is used in combination with Doxylamine for the treatment of nausea and vomiting in pregnancy. It’s worth noting that some people can get too much Pyridoxal-5-Phosphate supplementation in their systems which they cannot clear and it becomes toxic to them. This results in tight-band headaches which do go away when the supplementation of the P-5-P (B6) is stopped. These people might only be able to handle a few mg a day whereas others can take 25 mg or more without suffering the effects of its toxic build up. So pay attention to your reactions when you supplement with this nutrient.

Vitamin B12 (in the case of Folplex cyanocobalamin is used) is an essential nutrient, necessary for the production of red blood cells, DNA and cellular energy production. The low levels of vitamin B12 in milk, dairy and soy products, are required to be consumed in large quantities to meet the daily requirement. So, an alternative option society has turned to in this modern day and age is fortifying foods with vitamin B12 in order to attain the recommended nutrition intake. Non-vegetarian foods such as fish, meat, beef, poultry, eggs, liver are all good sources of vitamin B12. The microorganisms present in the intestinal tract of the human body can only synthesize a very little amount of vitamin B12. As a result there are likely much many more B12 deficient people who are unaware of their deficiency these days. The deficiency of vitamin B12 can cause fatigue, bone marrow suppression, megaloblastic anemia, abnormal erythropoiesis, skin hyperpigmentation, palpitations, glossitis, and infertility. Chronic deficiency causes progressive demyelination of nerve cells, peripheral neuropathy, areflexia, dementia and even psychosis in elderly patients. Deficiency during pregnancy may cause neural tube defects, ataxia, hypotonia and anemia.

It’s worth noting that there are 3 active forms of B12, hydroxocobalamin, methylcobalamin and adenosylcobalamin - all of which are much more absorbable and more immediately useful to the body than cyanocobalamin. Cyanocobalamin is known to have cyanide in it, be a man-made synthetic and not convert well within the body. And for many, taking this version of B12 is not only unhelpful to their health, in larger doses, it can also result in uncomfortable side effects. Hydroxocobalamin is the most well-tolerated active form of B12 which converts into methylcobalamin and adenosylcobalamin within the body. Hydroxocobalamin is the most rare form and much harder to find in supplements. Methylcobalamin is the most well-known active form of B12 and fairly available in vitamin products. And Adenosylcobalamin is known for its aid in muscle recovery among other things, but again, is rarer and more difficult to get in a product. 

If you choose to supplement with B12, choose an active form, even though it will cost you more money. The supplements will actually work for you because your body won’t need to do all of the downstream enzymatic conversions that cyanocobalamin requires - which many cannot do well anyway based on genetics. In the long run, you’ll get the health benefits you’re looking for and not be wasting your money on a product that doesn’t work to address your B12 needs.

Homocysteine (otherwise referred to as HCys) is a non-essential amino acid that derives from the biosynthesis and metabolism of methionine (Met). Homocysteine is a key metabolite involved in the biosynthesis and metabolism of methionine (Met), which plays an essential role in the physiological functions of cells. Normal plasma homocysteine levels for healthy adults has been established in 5 - 15 µmol/L. Imbalance in methionine metabolism leads to hyper-production and accumulation of homocysteine, a condition known as hyperhomocysteinemia or typically referred to as someone who has “high homocysteine” levels (or HHcys). It is an independent risk factor for cardiovascular diseases associated with atherothrombosis, lacunar infarction, cerebrovascular disease and peripheral artery disease. Hyperhomocysteinemia facilitates a high risk for osteoporosis induced bone fractures, rheumatism, increased bone resorption and neuronal pathologies like cognitive impairment (in elderly), depression including Alzheimer’s and Parkinson’s disease. Various meta-analysis studies have proved comprehensive associations between Alzheimer’s disease and homocysteine, folic acid, and vitamin B12 levels.

Hyperhomocysteinemia is caused by hereditary defects in metabolic enzymes of methionine (MTHFR, MTRR, etc.), deficiency of vitamins B6, B12 and folate or by feeding methionine enriched diets, high blood pressure, high creatinine and unfavorable lipid profile. In summary, high homocysteine is bad for many foundational health systems in your body, cardiovascular, immune and central nervous systems to name a couple big ones. Supplementing with methylfolate, active B12, B6 and TMG (Trimethylglycine) or DMG (Dimethylglycine) can all help reduce homocysteine levels if you find yours are too high.

Homocysteine metabolism occurs via three pathways:

  • re-methylation of homocysteine to form methionine by methionine synthase in a vitamin B12 and folate-dependent reaction
  • the trans-sulfuration pathway in which homocysteine, after addition of serine group, is converted to cystathionine in presence of cystathionine β-synthase (CBS) enzyme
  • re-methylation of homocysteine to methionine via betaine (TMG) and homocysteine methyltransferase (BHMT).

Thus, Hcys metabolism is dependent upon adequate stores of three dietary vitamins- folate, vitamin B12, and vitamin B6. Folate is a substrate for cellular production of tetrahydrofolate (THF), a precursor to 5-methyl-THF that is required for normal methionine synthase enzyme activity. Cobalamin or vitamin B12 is an organometallic compound (substances containing at least one metal-to-carbon bond in which the carbon is part of an organic group) and a key cofactor required for normal methionine synthase activity. Vitamin B6 or pyridoxine phosphate is a cofactor necessary for normal CBS enzyme activity. High homocysteine can be reduced significantly by nutraceutical intervention or by vitamin treatment to affected patients. Many research studies have suggested that except in vitamin B12 deficiency, folate treatment should be the most adequate therapy to reverse high homocysteine - particularly the nutrient, L-Methylfolate. Folate supplement improves endothelial function while folate in combination with pyridoxine treatment may contribute to the reduction of atherothrombotic risk. A greater reduction of vascular risks can be obtained with a combination of folate, vitamins B6 and B12.

Folplex can be used as a nutraceutical supplement for the treatment of high homocysteine, and to reduce the complications in cardiovascular and cerebrovascular diseases, osteoporosis induced bone fractures and cognitive impairments in elderly including Alzheimer’s disease. However, recent studies have suggested there are much better forms of these nutrients which more effectively treat the Hyperhomocysteinemia - these are the more bioavailable, ‘active’ forms of the vitamins which the body can directly use and does not have to go through the complex conversion processes which do not take place for many. 

These nutrients are:

  • L-Methylfolate – the most bioactive form of folate which can be directly absorbed by the body to immediately convert homocysteine into methionine
  • An active form of B12 – most consider methylcobalamin the best for homocysteine conversion, but the other two types will help with hyperhomocysteinemia if you don’t tolerate methylcobalamin
  • Pyridoxal-5-phosphate the active form of vitamin B6

Check out Methyl-Life’s™line of professional supplements if you’re looking for the above active forms of these vitamins at therapeutic doses which can treat your deficiency challenges.


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  5. Christen WG, Cook NR, Denburgh MV, Zaharris E, Albert CM, Manson JE. Effect of Combined Treatment With Folic Acid, Vitamin B6, and Vitamin B12 on Plasma Biomarkers of Inflammation and Endothelial Dysfunction in Women. J Am Heart Assoc 2018;7:1-9.
  6. Stone KL, Lui LY, Christen WG, Troen AM, Bauer DC, Kado D, Schambach C, Cummings SR, Manson JE. Effect of Combination Folic Acid, Vitamin B6, and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial. J Bone Miner Res 2017;32:2331–2338.
  7. Shen L, Ji HF. Associations between Homocysteine, Folic Acid, Vitamin B12 and Alzheimer’s Disease: Insights from Meta-Analyses. J Alzheimers Dis 2015;46:777-790.

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