Biochemistry, Water Soluble Vitamins


Article Author:
Jacqueline Lykstad


Article Editor:
Sandeep Sharma


Editors In Chief:
Amanda Oakley
Jules Lipoff
Shyam Verma


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
2/16/2019 10:15:18 AM

Introduction

Vitamins play a vital role in many biochemical functions in the human body and are essential components for maintaining optimal health. There are two main groups of vitamins – those that are fat soluble (easily stored in fat upon absorption) and those that are water soluble (washed out and not easily stored). Although adequate intake of all vitamins is important, due to the transient nature of water-soluble vitamins, regular intake is required to avoid deficiency. The water-soluble vitamins include Vitamin C and Vitamin B complex (thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folate, and cobalamin).

Vitamin B complex and vitamin C are found in many foods, especially vegetables and fruits, as well as dairy, meat, legumes, peas, liver, eggs, and fortified grains and cereals. In addition to serving as cofactors in biochemical reactions, vitamin B complex is vital for normal body growth and development, healthy skin, properly functioning of nerves and the heart, and red blood cell formation. The overall lack of water-soluble vitamins is rare in North America, though it can present in alcoholism, malabsorption syndromes, strict veganism, and malnourished states.

Issues of Concern

As stated above, the deficiency of water-soluble vitamins is rare in North America. However, deficiency may be a presenting feature in alcoholism, malnourishment, and malabsorption syndromes such as short-bowel syndrome. In short-bowel syndrome, there is the removal of a large portion of the small intestine for various reasons such as Crohn disease, necrotizing enterocolitis, traumatic injury, obstruction, or cancer. The small bowel is the site of absorption for all vitamins, and if a significant portion gets surgically removed (typically enough so that less than or equal to 200 cm of bowel remains), the body will be unable to absorb vitamins adequately. Treatment includes vitamin supplementation.[1]

Testing

Although it is tempting to simply obtain urine or serum levels of water-soluble vitamins, these reflect only presently circulating vitamin levels and are unable to approximate storage levels. Alternate forms of testing include immunoassays, chromatographic methods, chemical methods, high-pressure liquid chromatography, and capillary electrophoresis, depending on the vitamin being tested.[2] For vitamin B12 (cyanocobalamin) and folate deficiency, as discussed below, it is essential to obtain a complete blood cell count  (checking MCV, hematocrit, and hemoglobin) in addition to methylmalonic acid and homocysteine levels.

Clinical Significance

  • Thiamine (B1) is a cofactor (TPP) for multiple enzymes including pyruvate dehydrogenase, alpha-ketoglutarate, transketolase, and branched-chain ketoacid dehydrogenase, all of which are involved in glucose breakdown. Deficiency can result in adenosine triphosphate (ATP) depletion, and often affects highly aerobic tissues such as the brain, nerves, and heart first. With heart involvement, it is called wet beriberi and is characterized by high-output heart failure, edema, and dyspnea on exertion. When the nervous system is involved, it is called dry beriberi, which is characterized by polyneuritis and symmetrical muscle wasting. Damage to the medial dorsal nucleus of the thalamus and the mammillary bodies in the brain can result in a condition called Wernicke encephalopathy, recognized by the classic triad of confusion, ophthalmoplegia, and ataxia, or Wernicke-Korsakoff syndrome when accompanying confabulation, personality change, and memory loss is present.[3] Thiamine deficiency often is part of the presentation in alcoholics secondary to malnutrition and malabsorption, in addition to patients suffering from malnutrition. 
  • Riboflavin (B2) is a cofactor in redox reactions (FAD and FMN). Deficiency leads to cheilosis (inflammation of lips and fissures of the mouth) as well as corneal vascularization. Of note, ultraviolet (UV) light can destroy riboflavin; hence it is always packaged in opaque containers.[4]
  • Niacin (B3) is also utilized in redox reactions (as NAD+ and NADP+) and derives from tryptophan. Deficiency can present as pellagra, otherwise known as the 3-D’s: diarrhea, dermatitis, and dementia. Deficiency is rare in the USA but can occur in alcoholics and those with malnutrition. Niacin can be used to treat dyslipidemia, and a side effect is facial flushing, which can be avoided by treatment with aspirin.[5]
  • Pantothenic acid (B5) is a component of coenzyme A and fatty acid synthase, both of which are necessary for energy production and formation of hormones. Deficiency is characterized by dermatitis, enteritis, alopecia, and adrenal insufficiency.[6]
  • Pyridoxine (B6) is converted to pyridoxal phosphate (PLP) and is part of reactions including transamination, decarboxylation, and glycogen phosphorylase. It is critical for the formation of red blood cells and deficiency can result in sideroblastic anemia, hyperirritability, convulsions, peripheral neuropathy, and mental confusion. Peripheral neuropathy is a potential side effect of isoniazid, a key drug utilized in the treatment of tuberculosis, and it is customary to supplement treatment with B6.[7]
  • Biotin (B7) is necessary for the metabolism of protein, fats, and carbohydrates. Deficiency can lead to muscle pain, heart problems, anemia, and depression. Additionally, since biotin is a contributor to keratin, biotin has become popularized as a supplement to improve the quality of hair, skin, and nails. Large, unregulated doses of biotin can skew a variety of clinical tests, including thyroid tests T3 and T4, which can be either falsely elevated or falsely lowered depending on the particular assay; this is because nearly all immunoassays rely on the biotin-streptavidin attraction. This binding is also responsible for the biotin deficiency seen as a result of chronic consumption of large amounts of raw eggs whites, as raw egg whites contain a high volume of intact avidin, which strongly binds biotin. When egg whites are cooked, the avidin denatures and does not bind biotin as avidly.[8] Of note, TSH levels are unaffected by biotin supplementation.  
  • Folate (B9) is converted to tetrahydrofolate and is vital DNA and RNA synthesis. Deficiency can result in neural tube defects, prompting folate supplementation during pregnancy, and macrocytic (MCV>100), megaloblastic anemia. Folate deficiency may also be a feature in alcoholism.[9]
  • Cobalamin (B12) is essential for erythropoiesis and growth of the nervous system. Deficiency may lead to pernicious anemia and subacute combined degeneration of the spinal cord. The macrocytic, megaloblastic anemia from B12 deficiency presents similarly to folate deficiency, and to differentiate them it’s imperative to obtain serum homocysteine and methylmalonic acid levels. In folate deficiency, homocysteine will elevate, but methylmalonic acid levels will be normal. In vitamin B12 deficiency, both homocysteine and methylmalonic acid levels will present as elevated. Additionally, B12 deficiency will present with neurologic symptoms whereas folate deficiency will not.[10]
  • Vitamin C (Ascorbic Acid, Ascorbate) is needed for growth of collagen, wound healing, bone formation, enhancing the immune system, absorption of iron, strengthening blood vessels and acting as an antioxidant. When deficiency occurs, it can result in scurvy which can present with swollen and bleeding gums, loss of teeth, poor wound healing, and poor tissue growth.[11]

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Biochemistry, Water Soluble Vitamins - Questions

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A weight lifting enthusiast presents to the clinic with muscle pain, anemia, and depression since starting a new high protein diet based on large quantities of raw egg whites. His provider postulates that his symptoms could be due to vitamin deficiency. Which vitamin could be deficient?



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Vitamins are organic compounds, often classified based on their level of solubility. Vitamins that can dissolve in water are termed as water-soluble. Which of the following pairs are both water-soluble vitamins?



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A patient suffering from Crohn's disease decides to undergo extensive small bowel resection for symptom relief. Due to her newly shortened small intestine, her surgeon instructed her to supplement her diet with which of the following?



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Jim the pirate presents to your office with diffuse petechial rash, bleeding from the gums, and a poorly healing wound to his anterior shin. Upon questioning, the patient states that he has been out to sea for 3 months and has been sustained on a diet lacking fruits and vegetables. What vitamin deficiency is Jim displaying?



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An alcoholic G1P0 female at 6 weeks gestation presents to the clinic with megaloblastic anemia. Labs reveal MCV of 112, elevated homocysteine levels, and normal levels of methylmalonic acid. In addition to strict instructions to quit drinking, which vitamin is it essential to replenish?



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An 84-year-old female presents to the emergency department with her daughter for memory difficulties that have worsened over the past month. Per daughter, the patient lives alone and has not been taking care of herself since her husband passed away 5 months ago. Further questioning reveals four episodes of diarrhea per day. She denies fevers, chills, or dysuria. A neurological exam is unremarkable apart from moderate short term and long term memory loss. The heart is regular rate and rhythm; lungs are clear to auscultation bilaterally. Skin exam reveals an erythematous, flakey rash around the neck. As a perceptive physician, which vitamin deficiency is at the top of your differential?



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A 37-year-old male who recently returned from a trip to India presents to the emergency department with worsening hemoptysis, night sweats, and weight loss. Work up is positive for active tuberculosis and the patient is started on rifampin, isoniazid, pyrazinamide, and ethambutol. What vitamin supplement is recommended to prevent isoniazid-induced peripheral neuropathy?



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Biochemistry, Water Soluble Vitamins - References

References

Ajob L,Brännström I,Ott M,Werneke U, [Wernicke encephalopathy]. Lakartidningen. 2017 Sep 12;     [PubMed]
Balasubramaniam S,Christodoulou J,Rahman S, Disorders of Riboflavin Metabolism. Journal of inherited metabolic disease. 2019 Jan 24;     [PubMed]
Banka SS,Thachil R,Levine A,Lin H,Kaafarani H,Lee J, Randomized controlled trial of different aspirin regimens for reduction of niacin-induced flushing. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2017 Jun 15;     [PubMed]
Li L,Feng L,Jiang WD,Jiang J,Wu P,Kuang SY,Tang L,Tang WN,Zhang YA,Zhou XQ,Liu Y, Dietary pantothenic acid deficiency and excess depress the growth, intestinal mucosal immune and physical functions by regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in grass carp (Ctenopharyngodon idella). Fish     [PubMed]
Bhargava M,Bhargava A, Pyridoxine for patients suffering from drug-susceptible tuberculosis in India. Public health action. 2018 Jun 21;     [PubMed]
Poissonnier LA,Simpson SJ,Dussutour A, Observations of the     [PubMed]
Sanvisens A,Zuluaga P,Pineda M,Fuster D,Bolao F,Juncà J,Tor J,Muga R, Folate deficiency in patients seeking treatment of alcohol use disorder. Drug and alcohol dependence. 2017 Nov 1;     [PubMed]
Nagao T,Hirokawa M, Diagnosis and treatment of macrocytic anemias in adults. Journal of general and family medicine. 2017 Oct;     [PubMed]
Khalife R,Grieco A,Khamisa K,Tinmouh A,McCudden C,Saidenberg E, Scurvy, an old story in a new time: The hematologist's experience. Blood cells, molecules     [PubMed]
McLeish SA,Burt K,Papasouliotis K, Analytical quality assessment and method comparison of immunoassays for the measurement of serum cobalamin and folate in dogs and cats. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc. 2019 Jan 13;     [PubMed]
Braga CB,Vannucchi H,Freire CM,Marchini JS,Jordão AA Jr,da Cunha SF, Serum vitamins in adult patients with short bowel syndrome receiving intermittent parenteral nutrition. JPEN. Journal of parenteral and enteral nutrition. 2011 Jul;     [PubMed]

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