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Methylcobalamin and Folic Acid Combination Shows Efficacy for Deficiency

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Georgia Marrion ● 2 min read

Folate/folic acid (vitamin B9) and cyanocobalamin (vitamin B12) are water soluble vitamins essential for a range of physiological processes in the body, including red blood cell and deoxyribonucleic acid (DNA) synthesis, structural tissue repair, homocysteine metabolism and optimal cardiovascular, reproductive, immune and nervous system functionality.

Deficiency of these vitamins can be caused by insufficient dietary intake, reduced absorption due to poor intestinal health (e.g. gastritis, coeliac disease), genetic polymorphisms or use of certain medications.[1-4]

One multicentre prospective open label clinical study aimed to assess the effectiveness, tolerability and safety of oral folic acid and methylcobalamin (the methylated form of vitamin B12) intake in 498 male and female (289 and 209 respectively) adult subjects (mean age 43.26 + 11.98 years) exhibiting deficiencies of these vitamins.[1]

Each subject was given 5mg of folic acid and 750mcg of methylcobalamin together once daily for 12 weeks.

The efficacy of the intervention was assessed by measuring the mean percentage difference in symptoms including pallor, weakness, loss of appetite, irritability, myalgia and mouth ulcers at four, eight and 12 weeks of the study period compared with baseline scores.

Following four weeks of the intervention, the mean percentage symptom scores for pallor, loss of appetite, mouth ulcers, weakness, myalgia and irritability were statistically significant (p < 0.05), reducing by 42, 51, 67, 46, 51 and 76%, respectively. After eight weeks, mean scores reduced by 85, 99, 99, 94, 96 and 99% respectively, and by the end of the study period, there was total resolution of these symptoms.

Global assessment of treatment efficacy was reported as 99% very good and 1% good efficacy following the intervention, while global assessment of treatment tolerability was 98% exhibiting excellent and 2% good tolerability levels.

The safety assessment reported the rate of adverse events as 2%, comprising mild gastrointestinal disturbances that resolved over the study period and did not require early treatment cessation.

The authors stated that the well-tolerated and safe intervention ‘..provided quick onset of relief with regard to complete resolution of clinical signs and symptoms of vitamin deficiency’ in all subjects by the end of the treatment period.

This study provides strong evidence of the efficacy of folic acid and methylcobalamin for the treatment of common folic acid and vitamin B12 deficiency signs and symptoms.


  1. Maladkar M, Awatramani M, Samel UD. Real-world experience with fixed dose combination of folic acid and methylcobalamin combats B-vitamin deficiency and restores quality of life. Int J Gynecol Obstet 2016;2(6):2-5. [Full Text]
  2. National Health and Medical Research Council. Folate, 2014. [Link]
  3. National Health and Medical Research Council. Vitamin B12, 2014. [Link]
  4. Oxetenko AS, Murray JA. Celiac disease: ten things that every gastroenterologist should know. Clin Gastroenterol Hepatol 2015;13(8):1396-1404. [Full Text]


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Georgia Marrion

Georgia is a naturopath and nutritionist with 15 years’ experience who specialises in women’s health, particularly hormone imbalance and fertility and conception issues as well as and pregnancy and post-partum support. Georgia runs her own naturopathic and nutritional fertility and women’s health clinical practice and is an experienced health and nutrition writer.