Vitamin B deficiencies and treatment

Vitamin deficiency

There are eight essential B vitamins that cannot be synthesised in the body and hence need to be ingested daily.

Guidelines by the Merck Vitamin B Advisory Board

Vitamins are organic compounds that are essential for normal physiological functions and the maintenance of optimal health. They cannot be synthesised by the body and hence are required in small quantities in the diet and finally a deficiency thereof may cause specific nutritional medical disorders.1,2

The B-group (or B-complex) vitamins act as important co-enzymes in numerous metabolic processes and help the body convert carbohydrates into glucose for energy production, as well as to metabolise proteins and fats. B vitamins are also needed for the maintenance of healthy skin, hair, eyes, the liver and nervous system. 3-7 Some of the B vitamins are involved in the synthesis of red blood cells, neurotransmitters and nucleic acids such as RNA and DNA.1,6,7 Refer to Figure 1. There are eight essential B vitamins that cannot be synthesised in the body and hence need to be ingested daily. Of these, deficiencies in the so-called BIG 5 (B1, B3, B6, B9, and B12) can result in serious medically defined disorders. 2 Table 1.

table-1

A well-balanced diet, including both plant and animal-based foods, will prevent the occurrence of Vitamin B deficiencies. 1However, there are certain conditions that may predispose a person to the development of a vitamin B deficiency by either decreasing their intake or absorption of the B vitamins and/or increasing their need for or excretion of the B vitamins. Vitamin B deficiencies seldom occur in isolation.1 Active supplementation of vitamins should generally only be used to correct documented deficiencies, after which a well-balanced diet should be resumed to provide all necessary nutrients. 1Daily requirement of some of the B vitamins is listed in Table 2.table-2

CONDITIONS THAT PREDISPOSE TO VITAMIN B DEFICIENCIES

The elderly

Certain chronic medications can increase risk for a Vitamin B deficiency.18 These medications can decrease absorption, deplete stores, and increase clearance of the B vitamins.3-7,18-21 See Figure 2. Higher doses and prolonged administration (> 3 years) of metformin has been significantly associated with an increased risk of Vitamin B12 deficiency. 18Although the exact mechanism is unknown, metformin is thought to compete with Vitamin B12 at the ileal receptor sites and thus decrease its absorption.18 Gastric acid suppressive agents, such as H2-receptor blockers and proton pump inhibitors, are another group of medications that are often used long-term and that have been linked to Vitamin B12 deficiency. 18These medications cause a hypochlorhydric state, which results in malabsorption of protein-bound B12.18

table-3

Medication 

Certain chronic medications can increase risk for a Vitamin B deficiency.18 These medications can decrease absorption, deplete stores, and increase clearance of the B vitamins.3-7,18-21 See Figure 2. Higher doses and prolonged administration (> 3 years) of metformin has been significantly associated with an increased risk of Vitamin B12 deficiency. 18Although the exact mechanism is unknown, metformin is thought to compete with Vitamin B12 at the ileal receptor sites and thus decrease its absorption.18 Gastric acid suppressive agents, such as H2-receptor blockers and proton pump inhibitors, are another group of medications that are often used long-term and that have been linked to Vitamin B12 deficiency. 18These medications cause a hypochlorhydric state, which results in malabsorption of protein-bound B12.18

figure-2

figure-3

Malabsorption

As B vitamins cannot be manufactured by the body and not stored in large amounts, they need to be ingested on a daily basis.3-8,28 Gastrointestinal absorption of the B vitamins takes place mainly in the small intestine and there are many disorders that can negatively impact their uptake and result in deficiencies.24,28-31 See Figure 3. Vitamin B12 specifically is absorbed through a complex process requiring normal functioning of several areas of the gastrointestinal tract.18 Pepsin and hydrochloric acid separate free B12 from the protein bound B12 compound in the stomach. Free B12 then combines with R-proteins secreted from the salivary glands and gastric mucosa. This B12-R-protein complex travels to the small intestine where free B12 is released by pancreatic enzymes in the alkaline environment. The released B12 then combines with intrinsic factor and passes through to the ileum where it is absorbed by the enterocytes.18 Any alterations in the function and anatomy of the gastrointestinal tract such as gastric or ileal resection, inflammatory disorders, malabsorptive disorders, hypochlorhydria, a lack of intrinsic factor (Pernicious Anaemia) can therefore lead to Vitamin B12 malabsorption and deficiency.18                       

Excessive alcohol intake

Malnutrition and micronutrient deficiencies are common in chronic alcoholics.32 30-80 % of alcoholics have thiamine deficiency, 50 % have pyridoxine deficiency, 35 % have niacin deficiency and 6-80 % have folic acid deficiency.32 Severe vitamin deficiencies (Vitamin B1, B3, B6, and B12) in chronic alcoholics may result in severe functional impairment and tissue damage, particularly in the brain.32 Excessive alcohol consumption not only decreases the intake and absorption of B vitamins, but it also interferes with the storage, metabolism, utilisation and excretion of these vitamins.32 See Figure 4.

figure-4

HIV/AIDS

B vitamin deficiencies are widely seen in HIV, even in asymptomatic patients.34,35 See Table 4. The B vitamin deficiencies in these patients are most likely due to the cachexia and catabolic state characteristic of AIDS. 36In fact, HIV-infected patients require levels of B vitamins in multiples of the recommended dietary allowance (RDA) to achieve normal plasma levels.34 Malabsorption of Vitamin B12 occurs in HIV/AIDS patients and is due to many mechanisms including AIDS-related inflammation of the small intestine, gastric acid hyposecretion and production of antibodies to intrinsic factor.34

TABLE-4

DIAGNOSIS OF VITAMIN B DEFICIENCIES 

Severe deficiencies of some of the B vitamins may result in recognised disease entities such as Pellagra, Beri-Beri and Wernicke’s encephalopathy, megaloblastic anaemia and peripheral neuropathy.1 However, the non-specific symptoms of milder deficiencies such as headache, confusion, weight loss, and fatigue may require a high index of suspicion to make an accurate diagnosis. See Figure 5 for symptoms of B vitamin deficiencies. Multiple Vitamin B deficiencies are quite common.1 Therefore, if at least one B vitamin is found to be deficient, other B vitamin deficiencies should be considered and excluded.1 Also, a simple ‘gold standard’ diagnostic test may not be available – as is the case with Vitamin B12.9 When a B12 deficiency is suspected, the initial laboratory assessment includes serum B12 concentrations, a full blood count and a blood film examination to check for megaloblastic anaemia (which is often not seen in mild cases of B12 deficiency).9 There is also no universally accepted serum Vitamin B12 cut-off to define deficiency – the WHO recommends the value of < 150 pmol/L, however, higher levels of 220 to 258 pmol/L based on more sensitive indicators of B12 status (raised homocysteine and MMA levels) have been suggested.9 Refer to Table 5 for diagnostics measurements for Vitamin B deficiencies.

TABLE-5* TDP effect reflects the extent of unsaturation of transketolase enzyme with thiamine diphosphate, the main metabolically active form of thiamin (also known as thiamine pyrophosphate).28 Now considered an inadequate method as it is nonspecific and less sensitive than erythrocyte TPP38

** Sensitive to diet, so may not reflect long-term status. Not specific to Vitamin B12 deficiency as affected by low Vitamin B6 and B9 levels. TPP = thiamine pyrophosphate, PLP = pyridoxal 5’ phosphate, MMA = methylmalonic acid.

FIGURE-5

TREATMENT

Active replacement treatment should be instituted in documented/diagnosed vitamin deficiencies. Since Vitamin B deficiencies seldom occur in isolation, multiple deficiencies should be suspected and investigated.1 In cases where underlying conditions or chronic medication usage places patients at continued risk, there should be ongoing vitamin replacement therapy.18 The stricter control of vitamin treatments and supplements by the Medicine Control Council (MCC) puts “decision-making” and “treatment protocol” back into the hands of the healthcare professional, who is best able to diagnose deficiencies, manage and monitor patient’s progress. See Table 6 for guidelines on Vitamin B replacement therapy.

TABLE-6

 

CONCLUSION

B vitamins are essential for important physiological functions and are significant contributors to the maintenance of optimal health.1 Generally, a well-balanced diet will prevent Vitamin B deficiencies; however certain conditions and/or the use of chronic medication may predispose patients to low vitamin levels.1,3-7 Active treatment should be instituted in documented/diagnosed vitamin deficiencies. In cases where underlying conditions or chronic medicine usage places patients at continued risk, there should be ongoing vitamin replacement therapy.18

REFERENCES:

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  3. University of Maryland Medical Center. Vitamin B1 (Thiamine). [Online] 2015 Aug 6 [cited 2016 Apr 18]. Available from: URL: http://umm.edu/health/medical/altmed/supplement/vitamin-b1-thiamine.
  4. University of Maryland Medical Center. Vitamin B3 (Niacin). [Online] 2015 Aug 6 [cited 2016 Apr 18]. Available from:URL: http://umm.edu/health/medical/altmed/supplement/vitamin-b3-niacin.
  5. University of Maryland Medical Center. Vitamin B6 (Pyridoxine). [Online] 2015 Aug 5 [cited 2016 Apr 18]. Available from: URL: http://umm.edu/health/medical/altmed/supplement/vitamin-b6-pyridoxine.
  6. University of Maryland Medical Center. Vitamin B9 (Folic acid). [Online] 2015 Aug 5 [cited 2016 Apr 18]. Available from: URL: http://umm.edu/health/medical/altmed/supplement/vitamin-b9-folic%20acid.
  7. University of Maryland Medical Center. Vitamin B12 (Cobalamin). [Online] 2015 Oct 19 [cited 2016 Apr 18]. Available from: URL: http://umm.edu/health/medical/altmed/supplement/vitamin-b12-cobalamin.
  8. Drouin G, Godin J-R, Pagé B. The Genetics of Vitamin C Loss in Vertebrates. Curr Genomics 2011;12:371-378.
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  15. van der Wielen RPJ, Löwik MRH, Haller J, van den Berg H, Ferry M, van Staveren WA. Vitamin B-6 Malnutrition Among Elderly Europeans: The SENECA Study. J Gerontol BIOL SCI 1996; 51A (6):B417-B424.
  16. Kjeldby IK, Fosnes GS, Ligaarden SC, Farup PG. Vitamin B6 deficiency and diseases in elderly people – a study in nursing homes. BMC Geriatrics 2013; 13:13.
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  18. da Silva L, McCray S. Vitamin B12: No One Should Be Without It. Pract Gastroenterol 2009:34-46.
  19. Cass H. A Practical Guide to Avoiding Drug-Induced Nutrient Depletion. Nutr Rev Arch [Online] 2013 [cited 2016 May 9]. Available from: URL: http://nutritionreview.org/2013/04/practical-guide-avoiding-drug-induced-nutrient-depletion/.
  20. Mintzer S, Skidmore CT, Sperling MR. B-vitamin deficiency in patients treated with antiepileptic drugs. Department of Neurology Faculty Papers. Paper 48. [Online] 2012 [cited 2016 May 9]. Available from: URL: http://jdc.jefferson.edu/neurologyfp/48.
  21. Bobroff LB, Lentz A, Turner RE. Food/Drug and Drug/Nutrients Internations: What You Should Know About Your Medications. University of Florida. [Online] 2009 [cited 2016 May 9]. Available from: URL: http://www.ifas.ufl.edu/pdffiles/He/HE77600.pdf.
  22. DiBaise JK. Nutritional Consequences of Small Intestinal Bacterial Overgrowth. Pract Gastroenterol 2008;69:15-28.
  23. Ghorbel IB, Hajji R, Feki NB, Salem TB, Lamloun M, Houman MH. Two Exceptional Complications Revealing Celiac Disease: Ischemic Cardiomyopathy and Pellagra. Int J Celiac Dis 2015; 3(1):31-32.
  24. National Institutes of Health. Vitamin B6. Fact Sheet for Health Professionals. [Online] 2016 Feb 11 [cited 2016 May 9]. Available from: URL: https://ods.nih.gov/factsheets/VitaminB6-HealthProfessional/.
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  29. Prousky JE. Is Vitamin B3 Dependency a Causal Factor in the Development of Hypochlorhydria and Achlorhydria? J Orthomolecul Med 2001; 16(4):225-237.
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  31. National Institutes of Health. Folate: Dietary Supplement Fact Sheet. [Online] 2016 Apr 20 [cited 2016 May 10]. Available from: URL: http://ods.od.nih.gov/factsheets/Folate-HealthProfessional/.
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  35. Müri RM, Von Overbeck J, Furrer J, Ballmer PE. Thiamin deficiency in HIV-positive patients: evaluation by erythrocyte transketolase activity and thiamine pyrophosphate effect. Clin Nutr 1999; 18(6):375-378.
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  37. Semeere AS, Nakanjako D, Ddungu H, Kambugu A, Manabe YC, Colebunders R. Sub-Optimal Vitamin B-12 Levels among ART-Naïve HIV-Positive Individuals in an Urban Cohort in Uganda. PLoS One 2012; 7(7):e40072.
  38. Castro L, Goldani LZ. Iron, folate and vitamin B12 parameters in HIV-1 infected patients with anaemia in southern Brazil. Trop Doct 2009; 39(2):83-85.
  39. Mayo Clinic. Mayo Medical Laboratories. Test ID: TDP: Thiamin (Vitamin B1), Whole Blood. [Online] [cited 2016 May 16]. Available from: URL: http://www.mayomedicallaboratores.com/test-catalog/Clinical+and+Interpretive/85753.

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