The B Vitamin Series, Vitamin B9

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Vitamin B9, also known as folic acid or folate, is a water-soluble vitamin and is part of the vitamin B complex group. In the 1920s, scientists believed folate deficiency and anaemia were the same condition. In 1931, researcher Lucy Wills conducted a study that indicated anaemia during pregnancy could be reversed with brewer's yeast. B9 was named as the corrective substance in brewer's yeast in 1937. In 1941, Herschel Mitchell, Esmond Snell, and Roger Williams isolated B9 by extracting it from spinach leaves. In 1943, Bob Stokstad isolated the pure crystalline form, and determined its chemical structure, where key metabolic uses of the nutrient could then be identified and characterized. In the 1990’s, national health organisations acknowledged that, despite the availability of B9 in foods, many people struggled to hit daily B9 requirements, leading to manufacturing alterations and the implementation of the folate fortification program.

What is the prevalence of vitamin B9 deficiency?

The prevalence of vitamin B9 deficiency is extremely variable, with deficiency being most common in more undeveloped countries that do not use folic acid fortification of cereal-grain products. Analysis from national surveys in multiple countries state that B9 deficiency can be a serious public health problem if fortification is not a popular processing method.
From those that are diagnosed with B9 deficiency, the most common groups are pre-school children (~33.8%), pregnant women (~25-49%, dependent on country), adults (~24.5%), and older people (~15%) [1]. However, since the mandatory folic acid fortification practices have been enforced (1996-98), it is rare to find serum and red blood cell folate concentration survey data that shows high deficiency rates [2][3].
Dietary inadequacy is the main cause of B9 deficiency, but other factors can cause or exaggerate the problems. Studies show that chronic alcohol consumption is associated with diminished absorption of folate which can lead to B9 deficiency. Alcohol exposure impairs B9 absorption by inhibiting expression of the reduced B9 carrier and decreasing the hepatic uptake and renal conservation of circulating vitamin B9 [4].

Smokers may also be damaging their B9 status, with a study showing B9 concentrations were about 15% lower in smokers compared to non-smokers [5]. Pregnancy can also affect B9 status, with B9 requirement’s significantly increasing during pregnancy to assist the demand for accelerated cell replication and growth of fetal, placental, and maternal tissues [6].

What foods contain vitamin B9?

The best plant-based sources are:

  • fortified cereals
  • dark leafy greens
  • rice
  • spinach
  • asparagus
  • broccoli
  • citrus fruits
  • lentils/beans
  • avocado
  • okra
  • brussel sprouts.

The best animal-based sources are:

  • beef
  • crab
  • egg.

Trials conducted over the last 20 years have produced inconclusive and varying results regarding dietary B9 bioavailability, as different B9 status parameters (fasting serum folate, erythrocyte folate, and plasma total homocysteine) seem to produce contrasting conclusions. The estimated bioavailability of B9 is 78% based on serum folate concentrations, 98% based on erythrocyte folate concentrations, and 60% based on homocysteine concentrations [7].

What are the symptoms of vitamin B9 deficiency?

The main symptom of B9 deficiency is megaloblastic anaemia, which leads to weakness, fatigue, difficulty concentrating, irritability, headache, heart palpitations, and shortness of breath. B9 deficiency can also lead to tongue soreness, ulcers, oral mucosa, changes in skin, hair, or fingernail pigmentation, and elevated blood concentrations of homocysteine.

How much do you need per day?

Age

Male

Female

Pregnancy

Lactating

0-6 months

65 mcg

65 mcg

   

7-12 months

80 mcg

80 mcg

   

1-3 years

150 mcg

150 mcg

   

4-8 years

200 mcg

200 mcg

   

9-13 years

300 mcg

300 mcg

   

14-18 years

400 mcg

400 mcg

600 mcg

500 mcg

19+ years

400 mcg

400 mcg

600 mcg

500 mcg

[8]

What are the health benefits of vitamin B9?

Vitamin B9 acts as a coenzyme in single-carbon transfers during the synthesis of nucleic acids (DNA and RNA) and metabolism of amino acids, as well as participating in the creation of S-adenosyl-methionine, a crucial methyl donor [9]. The methylation of deoxyuridylate to thymidylate is another B9 dependent reaction, critical to model DNA, and is necessary for appropriate cell division. If this reaction is not completed successfully, it may trigger a process that can cause megaloblastic anaemia [10].

As B9 is essential for DNA and RNA synthesis, it has been shown to have a pronounced effect on the prevention of neural tube defects. Neural tube defects result in malformations of the spine, skull, and brain during pregnancy. Evidence shows that when women consume folic acid (the supplemental form of B9) from conception to early pregnancy, there is a reduction of 25-30% in neural tube defect frequency (~50% of folate related defects) [11]. The Food and Nutrition Board advise women of consensual age to “consume 400 mcg of folate daily from supplements, fortified foods, or both in addition to consuming food folate from a varied diet” [8].

Vitamin B9 may also be beneficial for preventing or treating depression. Poor B9 status has been linked to depression, as well as a poor response to antidepressants. In a study of 2,948 people, aged 1-39 years old in the United States, serum and erythrocyte B9 concentrations were significantly lower in individuals with major depression compared to those who had never been depressed [12]. In addition, a study of 52 people with major depression showed that only ~7% of subjects with low serum B9 levels benefitted from antidepressant treatment compared with ~45% of those with adequate B9 intake [13]. A Cochrane Review concluded that “folate may have a potential role as a supplement to other treatment for depression” [14].

Vitamin B9 is found mainly in fortified cereals, dark leafy greens, rice, spinach, asparagus, broccoli, beef and eggs. It has benefits on preventing neural tube defects, depression and megaloblastic anaemia. A lack of vitamin B9 may result in weakness, fatigue, irritability, headache, heart palpitations, tongue soreness, ulcers, changes in skin, hair, or fingernail pigmentation, and elevated blood concentrations of homocysteine. Deficiency is not common in populations that have fortification programmes, but may still affect pregnant women, smokers, heavy drinkers, or those with poor dietary intakes. Supplementation of folic acid may be necessary for those that are worried about or diagnosed with vitamin B9 deficiency.

 

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  1. McLean E, de Benoist B, Allen LH. (2008). Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr Bull.
  2. Pfeiffer CM, Johnson CL, Jain RB, (2007). Trends in blood folate and vitamin B-12 concentrations in the United States, 1988-2004. Am J Clin Nutr.
  3. Colapinto CK, O'Connor DL, Tremblay MS. (2011). Folate status of the population in the Canadian Health Measures Survey. CMAJ.
  4. Halsted CH, Villanueva JA, Devlin AM, Chandler CJ. (2002). Metabolic interactions of alcohol and folate. J Nutr.
  5. Pfeiffer CM, Sternberg MR, Schleicher RL, Rybak ME. (2013). Dietary supplement use and smoking are important correlates of biomarkers of water-soluble vitamin status after adjusting for sociodemographic and lifestyle variables in a representative sample of US adults. J Nutr.
  6. Herbert V. Shils M, Olson JA, Shike M, Ross AC, (1999). Modern Nutrition in Health and Disease. 9th ed. Baltimore: Lippincott Williams & Wilkins
  7. Brouwer IA, van Dusseldorp M, West C, Meyboom S, Thomas CMG., Duran M, van het Hof KH, Eskes TKAB, Hautvast GAJ, Steegers-Theunissen RPM. (1999). Dietary Folate from Vegetables and Citrus Fruit Decreases Plasma Homocysteine Concentrations in Humans in a Dietary Controlled trial. J. Nutr.
  8. Institute of Medicine. Food and Nutrition Board. (1998). Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC, National Academy Press.
  9. Bailey LB, Gregory JF. (2006). Folate. Present Knowledge in Nutrition, International Life Sciences Institute.
  10. Carmel R. (2005). Folic Acid. Modern Nutrition in Health and Disease, Lippincott Williams & Wilkins:
  11. Pitkin RM. (2007). Folate and neural tube defects. Am J Clin Nutr
  12. Morris MS, Fava M, Jacques PF, Selhub J, Rosenberg IH. (2003). Depression and folate status in the US Population. Psychother Psychosom
  13. Papakostas GI, Petersen T, Mischoulon D, Ryan JL, Nierenberg AA, Bottiglieri T. (2004). Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression. J Clin Psychiatry
  14. Taylor MJ, Carney S, Geddes J, Goodwin G. (2003). Folate for depressive disorders. Cochrane Database Syst Rev

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