Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Zinc: A Synopsis of this Critical Trace Mineral

January 18th, 2022
How to cite this article:

Azer M, Azer M, Magsakay CR. Zinc: A Synopsis of this Critical Trace Mineral. 2022. Journal of Vita Columbia. 2(1).


Zinc is one of the most crucial and most abundant minerals in the human body. Like most minerals, its deficiency leads to non-specific signs and symptoms. While it is common though, it is crucial to the immune system of the body and its deficiency and toxicity can lead to hazardous states which may be catastrophic in one’s health.


Zinc is the second most abundant trace mineral in the human body after iron, and is present in every cell. (1) Zinc can be found in many animal and plant food sources, but its highest levels exist in shellfish, salmon, lobster, beef, pork, lamb, chicken, milk and milk products, eggs, lentils, beans, oats, peas, asparagus and mushrooms. (1) However, zinc from animal products is absorbed more efficiently than from plant-based products. (1)

The Role of Zinc in the Human Body

  • Zinc has an important role in gene expression, DNA and protein synthesis (1).
  • It aids in over 300 enzymatic reactions in digestion, nerve function and other metabolic reactions. (1) It also aids in immune function (1)
  • Zinc aids in collagen synthesis so it plays a crucial role in having a healthy skin and wound healing. In fact, skin has about 5% of zinc content in the human body. (1)
  • It’s used in growth and development (1)
  • It also has anti-inflammatory effect (1)
  • Zinc plays an essential role in bone formation and health (5)
  • Zinc may significantly reduce risk of age-related diseases, such as pneumonia, infection and age-related macular degeneration (AMD). (1)
  • It’s important to maintain healthy vision. (2)
  • It also acts significantly in blood clotting (2)
  • It improves thyroid function (2)

Zinc Deficiency:

Some groups are more at risk of zinc deficiency than others, such as sickle cell anemia patients (1), those with eating disorders (bulimia or anorexia) (1), patients with chronic kidney disease (1), people with alcohol abuse disorder (1), vegetarians and vegans. (1) Pregnant and lactating females (1), those with poor dietary intake (1), liver cirrhosis (2), gastrointestinal diseases (inflammatory bowel disease, short bowel syndrome, malabsorption (3), older infants (7-12 months old) who are exclusively breastfed (3), diabetes (3) and those with malignancy (3) are also susceptible to zinc deficiency.

It is estimated that around 2 billion people worldwide are deficient in zinc due to inadequate dietary intake. (1) Symptoms of mild zinc deficiency include diarrhea, decreased immunity, thinning hair, decreased appetite, mood disturbances, dry skin, fertility issues and impaired wound healing (1). In severe zinc deficiency, there is impairment in growth and development, delayed sexual maturity, skin rashes, chronic diarrhea, generalized hair loss, impaired wound healing, poor sense of taste and smell, irritability and behavioral changes (1, 2). Severe deficiency can also impair the immune system as it can depress neutrophils, macrophages and complement activity. (3) Also, it decreases lymphocytes proliferation and activation. This results in increased risk of pneumonia and other infections especially in extremes of age (3).

Since zinc deficiency impairs immune system function, it’s thought to cause over 450,000 deaths in children under 5 every year (1). In truly severe cases, it can also lead to acute diarrhea which is a significant cause of mortality among children in developing communities (3).

Treatment of Zinc Deficiency

The treatment for zinc deficiency is fairly simple. Firstly, the recommended daily dose is 11 mg for men and 8 mg for women (except pregnant and lactating who need around 14-19 mg daily). If a higher dose is needed, it should be recommended and monitored by physicians only; however, the daily dose should not exceed 40 mg to avoid toxicity. (2) The National Institutes of Health consider 40 mg of zinc a day to be the upper limit dose for adults and 4 mg of zinc a day the upper limit for infants under age 6 months. (4) The preferred means of administration are zinc citrate and zinc gluconate as these forms are more easily absorbed. (1)

Clinical Uses of Zinc:

There are several uses of zinc. Zinc is commonly used in hospitals as a treatment for burns, ulcers and other skin injuries. Also, for uncontrolled acute childhood diarrhea the World Health Organization and UNICEF recommend short-term zinc supplementation (20 mg of zinc per day, or 10 mg for infants under 6 months, for 10–14 days) (3). Many studies have even confirmed that zinc supplementation may improve many conditions such as Wilson’s disease, diabetes mellitus, depression, ADHD, macular degeneration, leprosy, warts, acne and gingivitis (2).

Zinc Toxicity:

Zinc toxicity can occur due to ingestion of 100 m daily or taking high doses for many consecutive years, this can double the risk of prostate cancer (2). Ingestion of 10 gm of zinc at once can be fatal (2).

Acute symptoms of zinc toxicity include GIT upset (nausea, vomiting, diarrhea, loss of appetite and abdominal cramps) and headaches. (1) A more chronic effect of zinc toxicity is a decline in HDL levels. (1)

Pharmacologic Interactions with Zinc:

A potential problem with zinc treatment however is that zinc supplements can interfere with other medications (2). For example, they decrease the absorption of some antibiotics like tetracycline sans quinolones. (2) Zinc supplements can also interfere with the absorption and action of penicillamine, decreasing its effect (3).

Taking high amounts of zinc can also affect the absorption of other nutrients such as copper and iron (1).  Zinc can increase the effect and the side effects of cisplatin. (2) On the other hand, zinc can be affected by medication, for example some diuretics such as thiazides increase urinary excretion of zinc, decreasing its level in blood. (3)


In conclusion zinc is required for life, while in deficiency states it may be easy to treat, zinc toxicity can lead to various signs and symptoms, up to and including cancer. Like many minerals that are used by the body, symptoms are vague and non-specific; however, there are certain key signs to look for, such as an impaired immune system, that elucidates the possibility of zinc deficiency.


  1. The Nutrition Source – Selenium., Harvard T.H. Chan – School of Public Health.,
  2. Raman, Ryan., 10 Signs and Symptoms of Iodine Deficiency., Healthline Nutrition, Nov. 2017.,
  3. Navarro-Alarcon M, Cabrera-Vique C. Selenium in food and the human body: a review. Sci Total Environ. 2008 Aug 1;400(1-3):115-41. doi: 10.1016/j.scitotenv.2008.06.024. Epub 2008 Jul 26. PMID: 18657851.
  4. Mangiapane E, Pessione A, Pessione E. Selenium and selenoproteins: an overview on different biological systems. Curr Protein Pept Sci. 2014;15(6):598-607. doi: 10.2174/1389203715666140608151134. Erratum in: Curr Protein Pept Sci. 2018;19(7):725. PMID: 24910086.
  5. Kang, D., Lee, J., Wu, C. et al. The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies. Exp Mol Med 52, 1198–1208 (2020).
  6. Jenkins DJA, Kitts D, Giovannucci EL, Sahye-Pudaruth S, Paquette M, Blanco Mejia S, Patel D, Kavanagh M, Tsirakis T, Kendall CWC, Pichika SC, Sievenpiper JL. Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2020 Dec 10;112(6):1642-1652. doi: 10.1093/ajcn/nqaa245. PMID: 33053149; PMCID: PMC7727482.
  7. Selenium – Fact Sheet for Health Professionals., National Institutes of Health- Office of Dietary Supplements., March 2021.,
  8. Shi, Ying., Yang, Wei., Tang, Xianwen., Keshan Disease: A Potentially Fatal Endemic Cardiomyopathy in Remote Mountains of China., Frontiers in Pediatrics – Pediatric Cardiology., March 2021.,
  9. Schepman, Karin., Engelbert, Raoul., Kashin Beck Disease: more than just osteoarthrosis., National Institutes of Health, U.S. National Library of Medicine., June 2010.,
  10. Moghaddam A, Heller RA, Sun Q, Seelig J, Cherkezov A, Seibert L, Hackler J, Seemann P, Diegmann J, Pilz M, Bachmann M, Minich WB, Schomburg L. Selenium Deficiency Is Associated with Mortality Risk from COVID-19. Nutrients. 2020 Jul 16;12(7):2098. doi: 10.3390/nu12072098. PMID: 32708526; PMCID: PMC7400921.
  11. Selenium,., WebMD – Vitamins and Supplements.,
  12. Thomas, Liji., Selenium Toxicity., News – Medical Life Sciences., April 2021.,
  13. Selenium., Medsafe – New Zealand Medicines and Medical Devices Safety Authority., July 2000.,
  14. picture reference: ResearchGate, October 2017.,

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Selenium: A Trace Mineral Critical For Several Physiologic Processes

January 18th, 2022
How to cite this article:

Azer M, Azer M, Pali RR. Selenium: A Trace Mineral Critical For Several Physiologic Processes. 2022. Journal of Vita Columbia. 2(1).


A non-metal with an atomic number of 34, selenium is on the periodic table as one of the fundamental elements of our universe. As in our universe, selenium is also a fundamental element of our bodies, forming enzymes that aid in DNA synthesis, thyroid hormone metabolism and is key in our reproductive function. So what happens when we are low on this crucial element in our bodies? What about if we go into toxicity? Read on to find out.


The human body needs a small amount of selenium; hence it is one of the trace minerals. (1) It can be found in many kinds of food such as oysters, Brazil nuts, halibut, tuna, eggs, sardines, sunflower seeds and chicken breasts. (2) However, the exact amount of selenium in plants depends on the selenium content of the soil they grow. (2) This soil content varies according to many factors such as rainfall, evaporation and pH level. (2) Selenium bioavailability varies according to the source and nutritional status of the subject, being significantly higher for organic forms of selenium. Selenium supplements can benefit subjects living in regions with low environmental selenium levels. Several strategies have been followed: (a) employment of selenium-enriched fertilizers; (b) supplementation of farm animals with selenium; (c) consumption of multimicronutrient supplements with selenium. Considering the various sources of selenium, Suppliers also need to provide more information on the specific type of selenium used in supplements. (3)

Selenium is a crucial component of many proteins and enzymes, some called (selenoproteins). These proteins help in DNA synthesis, protect against cell damage, thyroid hormones metabolism, and reproductive function in females and males (2).

Metabolism of Selenium

As earlier stated, selenium (Se) is an essential trace element for humans, plants and microorganisms. Inorganic selenium is present in nature in four oxidation states: selenate, selenite, elemental selenium and selenide in decreasing order of redox status. All biological systems convert these forms into more bioavailable organic forms. Mainly as the two seleno-amino acids, selenocysteine and selenomethionine. Humans, plants and microorganisms can fix these amino acids into proteins originating selenium-containing proteins by a simple replacement of methionine with selenomethionine, or “true” selenoproteins if a specific UGA codon genetically encodes the insertion of selenocysteine. (4)

From the diet, selenium obtained in organic forms (selenomethionine and selenocysteine) and inorganic forms (selenite and selenate) is taken up by the liver that synthesizes and exports selenoprotein P (SELENOP), which eventually circulates through the bloodstream. SELENOP, with multiple selenocysteine residues, transports selenium to other tissues and organs. The transported selenium is converted to selenophosphate by intracellular selenium metabolic pathways. In small-molecule metabolites formed by sequential methylation, selenium is excreted through exhalation and urine. Selenium plays biological roles predominantly as selenoproteins, synthesized by the selenium metabolic system. (5)

The Role of Selenium in the Human Body

  1. It has a strong antioxidant effect, protecting the cell from being damaged by free radicals.
  2. Decreases the risk of malignancy.
  3. Decreases the chances of heart disease.
  4. Prevention of mental decline.
  5. It is vital for thyroid function as it contains the highest amount of selenium in the human body.
  6. It boosts the immune system.
  7. Improves asthma symptoms.

Considering the role of selenium in the human body, we can see why its adequacy is essential, especially for certain groups more susceptible to selenium deficiency. These groups include patients with Graves or other thyroid diseases, patients who suffer from malignancies or weak immune systems, and pregnant women. (2)

More research is needed in certain areas where the role of selenium is essential. For example, research is lacking on the mechanisms through which selenium is involved in hepatocyte damage during hepatopathies. However, selenium potential as an antioxidant for preventing cardiovascular diseases (CVD) is promising. (6) However, additional long-term intervention trials are necessary. As a result, indiscriminate selenium supplements cannot be reliably recommended to prevent CVD in human beings. Some interesting findings reported an association of selenium intake with a reduced prevalence and risk for prostate and colon cancer. However, random trials for other cancer types are inconclusive. In conclusion, the general population should be cautioned against using selenium supplements to prevent hepatopathies, cardiovascular or cancer diseases. The benefits of selenium supplementation are still uncertain in these cases, and the indiscriminate use of supplements could generate an increased risk of selenium toxicity. (3)

Selenium Deficiency:

While selenium deficiency may be rare in the United States and Canada, around 1 billion people still suffer from it worldwide. (2) It is more common in China, Russia and some European countries. (1)

Some risk factors of selenium deficiency include living in areas with soil low in selenium level, especially in those who follow a vegan diet, dialysis patients, HIV patients and those with digestive disorders (such as inflammatory bowel disease). (2,7)

Symptoms of Selenium Deficiency
Selenium deficiency may be manifested as the following symptoms (1,2):

  • hair loss
  • nausea
  • vomiting
  • headaches
  • muscle weakness
  • fatigue
  • mental disturbance
  • infertility
  • weak immune system
  • seizures
  • coma

Severe deficiency of selenium can lead to Keshan disease or Kashin Beck disease. (1)

Keshan disease is named after a county in China where it was first reported in 1935. Keshan disease is a fatal type of cardiomyopathy responsible for high morbidity and mortality rates in China. (8) It can be acute or chronic, and while many theories have been discussed about the etiology, the main reason is believed to be selenium deficiency. (8) Patients suffering from Keshan disease show congestive heart failure, acute heart failure and cardiac arrhythmia. (8)

Kashin beck disease (KBD) is a chronic joint inflammatory disorder that can lead to disability. It is common in Siberia, North Korea and China, where around 1 million people are affected (9). When it strikes in childhood, it may lead to dwarfism, significantly if it affects children around two years.

The disease develops symmetrically, beginning with and mainly affecting the distal joints of upper and lower limbs, causing inflammation and damage. (9)

Diagnosis of Selenium Deficiency

  • The most commonly used measures of selenium status are plasma and serum selenium concentrations. (7)
  • The selenium level in blood or urine gives an idea about the recent intake. (7)
  • Analysis of nail or hair selenium content reflects long-term intake. (7)

Prevention & Treatment of Selenium Deficiency

  • 15 mcg is recommended from o to first six months of life. (11)
  • 20 mcg is needed from 6 months to three years old. (11)
  • From four to eight years old, 30 mcg is recommended daily. (11)
  • 40 mcg daily is good from nine to thirteen years old. (11)
  • The recommendation is for people older than fourteen years to ingest 55 mcg of selenium daily. (2)
  • Pregnant and lactating women need around 70 mcg daily; if suffering from pre-eclampsia, the dose can be increased up to 100 mcg for six months. (2, 11)

Selenium Deficiency & Covid-19:

Selenium deficiency has been associated with mortality risk from Covid 19; this is from studies made from samples taken from Covid 19 patients, showing a solid correlation pointing to an insufficient selenium availability for optimal selenoprotein expression. The selenium levels in surviving patients were higher than that in non-surviving patients. Also, because of the high importance of selenium in immune response, the mortality risk from a severe disease like sepsis or polytrauma is inversely related to selenium status (10)

Selenium Toxicity:

Despite the vital role of selenium, a high selenium level in plasma can be dangerous and fatal. (2) Above 900 mcg of selenium of daily ingestion can be toxic. (2)

Some indicators for selenium toxicity include (1,2):

  • bad breath
  • metallic taste
  • brittle nails
  • skin lesions
  • hair loss
  • dizziness
  • nausea
  • vomiting
  • tremors
  • muscle aches
  • facial flushing

Complicated severe cases may suffer from neurological symptoms, coronary heart disease and even up to death. (2)

The treatment of selenium toxicity involves mainly supportive care and stopping further exposure. There is no chelator or suitable antidote yet. (13)

Pharmacologic Interactions with Selenium:

Selenium boosts the effect of some medications such as; anticoagulants and sedatives. It decreases the effect of other medications like; statins, niacin, oral contraceptive pills and immunosuppressants. On the other hand, some supplements such as gold, zinc and Omega-3 fatty acids lower the efficacy of selenium. (12)


  1. The Nutrition Source – Selenium., Harvard T.H. Chan – School of Public Health.,
  2. Raman, Ryan., 10 Signs and Symptoms of Iodine Deficiency., Healthline Nutrition, Nov. 2017.,
  3. Navarro-Alarcon M, Cabrera-Vique C. Selenium in food and the human body: a review. Sci Total Environ. 2008 Aug 1;400(1-3):115-41. doi: 10.1016/j.scitotenv.2008.06.024. Epub 2008 Jul 26. PMID: 18657851.
  4. Mangiapane E, Pessione A, Pessione E. Selenium and selenoproteins: an overview on different biological systems. Curr Protein Pept Sci. 2014;15(6):598-607. doi: 10.2174/1389203715666140608151134. Erratum in: Curr Protein Pept Sci. 2018;19(7):725. PMID: 24910086.
  5. Kang, D., Lee, J., Wu, C. et al. The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies. Exp Mol Med 52, 1198–1208 (2020).
  6. Jenkins DJA, Kitts D, Giovannucci EL, Sahye-Pudaruth S, Paquette M, Blanco Mejia S, Patel D, Kavanagh M, Tsirakis T, Kendall CWC, Pichika SC, Sievenpiper JL. Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2020 Dec 10;112(6):1642-1652. doi: 10.1093/ajcn/nqaa245. PMID: 33053149; PMCID: PMC7727482.
  7. Selenium – Fact Sheet for Health Professionals., National Institutes of Health- Office of Dietary Supplements., March 2021.,
  8. Shi, Ying., Yang, Wei., Tang, Xianwen., Keshan Disease: A Potentially Fatal Endemic Cardiomyopathy in Remote Mountains of China., Frontiers in Pediatrics – Pediatric Cardiology., March 2021.,
  9. Schepman, Karin., Engelbert, Raoul., Kashin Beck Disease: more than just osteoarthrosis., National Institutes of Health, U.S. National Library of Medicine., June 2010.,
  10. Moghaddam A, Heller RA, Sun Q, Seelig J, Cherkezov A, Seibert L, Hackler J, Seemann P, Diegmann J, Pilz M, Bachmann M, Minich WB, Schomburg L. Selenium Deficiency Is Associated with Mortality Risk from COVID-19. Nutrients. 2020 Jul 16;12(7):2098. doi: 10.3390/nu12072098. PMID: 32708526; PMCID: PMC7400921.
  11. Selenium,., WebMD – Vitamins and Supplements.,
  12. Thomas, Liji., Selenium Toxicity., News – Medical Life Sciences., April 2021.,
  13. Selenium., Medsafe – New Zealand Medicines and Medical Devices Safety Authority., July 2000.,
  14. picture reference: ResearchGate, October 2017.,

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Iron: Maintaining Homeostasis and Implications of Deficiency & Toxicity

January 18th, 2022
How to cite this article:

Yeldhose BS and Grewal VP. Iron: Maintaining Homeostasis and Implications of Deficiency & Toxicity. 2022. Journal of Vita Columbia. 2(1).


Iron deficiency anaemia is very common across the globe, accounting to 50% of all cases of anaemia. It is one of the common preventable causes of anaemia. Iron is a vital micronutrient required for life sustaining physiological processes. It exists in two forms – haem (animal-based) and non-haem (plant-based). It is absorbed in the duodenum. There is no defined mechanism in place for excretion of iron. Hence, a strict balance of iron intake and absorption is essential to maintain iron homeostasis and thereby prevent iron deficiency and toxicity. This article will focus on the role of iron in human body and the implications it has on its deficiency and toxicity.


A normal adult male has around 3.5g of iron in the body, of which 65% is found in hemoglobin [9]. The rest of the iron is distributed among myoglobin, enzymes, cytochrome, liver, macrophages, reticuloendothelial system, and bone marrow [9]. A normal diet has around 15-20mg of iron. However, our body absorbs only around 1-2mg of iron a day [9]. Our body, on average, needs 20-25mg of iron per day to function [7].  To mention a few, it acts as an oxygen carrier to tissues using hemoglobin and myoglobin, as electron carriers within cells, involved in several enzymatic functions, detoxification of foreign substances in the liver, and so on [5]. Given the high demand for iron in our body, the probability of getting iron deficiency is high. On the contrary, our body lacks a mechanism for excretion of absorbed iron. The main source of iron loss from our body is through bleeding, menstruation, pregnancy, and exfoliation of epithelial surfaces such as skin, genitourinary tract, and gastrointestinal tract. [1] Hence, taking iron in excess amounts predispose us to iron toxicity. Therefore, a crucial balance of iron homeostasis is required for adequate bodily function.

Dietary Sources of Iron

Dietary sources of iron exists in two forms – haem (animal-based) and non-haem (plant based). The richest haem source of iron is lean meat and seafood and non-haem source are nuts, beans, vegetables, and fortified grain products [10]. Public health measures such as fortifying staple food with iron is yet another source [6]. Oral iron supplement is also among the common sources of iron [10]. Fascinatingly, our body also recycles iron from aging erythrocytes, exchanging iron from iron containing enzymes and from iron stores [7].

Table 1.0: Daily Recommended Dietary Iron Intake [10]


Male Female Maximum daily intake Pregnancy Lactation





7 – 12mo


1 – 3yrs


4 – 8yrs


9 – 13yrs


14 – 18yrs






19 – 50yrs





>50yrs 8mg


Iron Homeostasis

Iron is mainly absorbed in the duodenum [12]. There are two forms of iron – haem iron which exists in the ferrous form (Fe2+) and non-haem iron, which exists in the ferric form (Fe3+) [1]. Haem iron is readily absorbed by the enterocytes [1]. Non-haem iron, on the contrary, should be first reduced to ferrous form before being absorbed [1]. This is achieved by the action of low gastric pH and by the enzyme named ferric reductase duodenum cytochrome B found in the intestinal membrane [1]. Once converted to ferrous form, it is then readily absorbed to the bloodstream [1].

Iron levels in the body is mainly regulated by controlling its absorption as there is no set mechanism in place for its excretion. A main protein involved with this is hepcidin, secreted by the liver [1]. Its secretion is increased when body iron stores are high, which then inhibits further iron absorption [1]. One drawback with hepcidin is that, it is also secreted at times of inflammatory processes, and causes reduced iron absorption, leading to iron deficiency anaemia [1].

Once the iron is absorbed, it is taken up by transferring which acts as a transport protein to transfer iron to cells or bone marrow for erythropoiesis. Our body also recycles iron from the aging RBCs with the help of macrophages, making then available for synthesis of new RBC [12].

Iron Deficiency:

Iron deficiency is defined as when the total body iron stores are low [2]. Iron deficiency anaemia on the other hand is when the iron deficiency starts to affect erythropoiesis [2]. 30 – 50% of all anaemia is caused by iron deficiency [8]. Children of age <5, women of childbearing age and woman who are pregnant are at the highest risk due to increased iron demands [7]. The causes of iron deficiency are diverse and is demonstrated in the Figure 1., adopted from the article Iron deficiency anaemia revisited [4].

There are two forms of iron deficiency – absolute and functional iron deficiency [7]. Absolute iron deficiency is the situation where the total iron stores in the body are low [7]. Functional iron deficiency on the other hand is when the total body iron stores are normal, but iron supply to the bone marrow is low [7]. Such a situation occurs during phases of acute or chronic inflammation [7].

Iron deficiency most often presents with no symptoms and is very often an incidental finding in laboratory tests. However, symptoms of iron deficiency are various. Iron deficiency results in reduced erythropoiesis which causes symptoms of hypoxia such as fatigue, exertional shortness of breath, increasing breathlessness at rest, vertigo, syncope, headache, tachycardia, and cardiac systolic murmur [7]. Reduced erythropoiesis also causes skin, conjunctiva, and nail beds to appear pale [7]. Iron deficiency also affects cells with rapid turnover. This presents with symptoms such as dry and rough skin, dry and damaged hair, moderate and diffuse alopecia and koilonychia [7]. Mild-to-moderate cases of iron deficiency causes loss of tongue papillae [7]. Severe iron deficiency causes atrophic glossitis, shortness of breath at rest, angina pectoris and hemodynamic instability [7].

Iron deficiency anaemia, left untreated, can eventually lead to complications such as reduced physical performance, poor work productivity, global cognitive decline, and dementia [7]. It increases the risk of infection, depression and pregnancy complications [13]. Iron deficiency during perinatal period causes delayed neurocognitive development [7].

Investigation for iron deficiency starts with laboratory evaluation which will show low hemoglobin, low MCHC, low MCV, and low transferrin saturation [13]. The total iron binding capacity (TIBC) will be raised [3]. Ferritin is yet another parameter that is measured during investigation for iron deficiency. Its level establishes the total body iron stores; a low level of ferritin is seen at times of iron deficiency [3]. However, inflammatory conditions such as acute infection, malignancy and collagen diseases causes ferritin to be acutely raised [13]. In such cases when ferritin becomes an unreliable predictor for iron stores, bone marrow biopsy and iron staining is the gold standard [13]. However, this procedure is rarely performed due to its invasiveness [13]. Once iron deficiency is established, further testing could be performed to identify its causes.

Given the global burden of iron deficiency and its impact on human health, prevention of iron deficiency is a crucial public health need. Public health measures such as increasing availability and consumption of iron rich food and fortifying staple food with iron has been implemented in several countries [4]. Supplementing with oral iron tablets to at risk groups is also an effective strategy [4]. Along with consuming enough quantity of iron, co-consuming ascorbic acid rich food enhances absorption of the consumed iron [4]. On the contrary, calcium, cereal, tea, and coffee inhibits iron absorption. Hence, consumption of these food at different times of consumption of iron rich food enhances iron absorption [4]. These simple public health measures can have significant impact on controlling global iron deficiency anaemia [4].

Once the diagnosis of iron deficiency anaemia is established, acute correction of iron deficiency is best achieved by providing with supplements. Response to oral iron supplements is seen within two weeks, however supplements should be continued for atleast six months to establish iron stores are replenished [13]. On the other hand, during situations of chronic inflammatory conditions, chronic heart diseases, inflammatory bowel disease, and chronic kidney disease, patients does not respond sufficiently to oral replacements [4]. During such situations, IV iron supplements are the preferred choice [4]. Other situations where IV iron is indicated includes malabsorption such as celiac disease, intolerance to oral iron, post-gastrectomy and achlorhydria [13]. Once iron deficiency is corrected acutely, further investigations and treatment is targeted at the cause for iron deficiency.

Iron Toxicity:

Children consuming adult preparation of iron is among the most common cause for iron toxicity [14]. In 2015, AAPCC has reported 4072 cases of iron toxicity, of which 3211 were unintentional and 2036 were in children less than the age of 5 [14]. The amount of iron that is tolerated by an individual is dependant on his/her body weight [14]. Table 2 describes the amount of iron that can be consumed a day and the level of toxicity it causes [14]. Table 3 is yet another data set that explains the level of toxicity based on the iron level found in blood sample taken [14]. Iron levels in blood should be measured within 4-6hrs after consumption [14]. This is because iron that is circulating in blood is soon absorbed and deposited in the liver [14]. Hence, measurements taken after this peak is unreliable.

Table 2.0: Daily Consumption of Iron that Can Lead to Toxicity

Iron consumption per day Level of toxicity
<20mg/kg/day Non-toxic
20-60mg/kg/day Moderate toxicity
>60mg/kg/day Severe toxicity; causes morbidity and mortality

Table 3.0: Iron Levels in the Blood that Can Cause Toxicity

Iron level Level of toxicity
<350microgram/dL Minimal toxicity
350 – 500microgram/dL Moderate toxicity
>500microgram/dL Severe toxicity

The toxic effect of iron is divided into five stages as described in Table 5 [14]. However, one may not go through all the five stages, and one may not survive to reach to the fifth stage [14]. 

Table 4.0: The Five Stages of Iron Toxicity

Stage Time post ingestion Symptoms
Stage 1 0.5 – 6hrs Abdominal pain, vomiting, diarrhoea, hematemesis, hematochezia
Stage 2 6 – 24hrs Gastrointestinal symptoms resolve
Stage 3 6 – 72hrs Recurrence of gastrointestinal symptoms, shock, metabolic acidosis. Iron induced coagulopathy, hepatic dysfunction, cardiomyopathy, renal failure
Stage 4 12 – 96hrs Elevation of aminotransferase and results in liver failure
Stage 5 2 – 8wks Consequences from healing of gastric mucosa 🡪 pyloric and proximal bowel scarring and obstruction

Complications from iron toxicity includes liver necrosis, cardiogenic shock, myocardial dysfunction, coma, seizure, coagulopathy, esophagitis, anaemia, ARDS, stricture formation of intestine and gastric perforation [14]. In terms of management, people who have consumed toxic levels of iron, and has been asymptomatic for 4-6hrs does not require any treatment [14]. However, those who had developed GI symptoms and presenting with normal vital signs needs to be observed as they might be in the second stage of iron toxicity [14]. However, if the individual is exhibiting symptoms of haemodynamic instability, they will need aggressive treatment in the intensive care unit [14].


Iron is an important micronutrient performing various crucial function in human body, with its main function being oxygen transport. Most of the iron in human body is found in hemoglobin. Iron is absorbed in the proximal duodenum. Both iron deficiency and toxicity have serious health impacts. Hence, a strict balance of iron levels in the body is crucial for a healthy body.


  1. Abbaspour, N., Hurrell, R., & Kelishadi, R. (2014). Review on iron and its importance for human health. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 19(2), 164–174.
  2. Bermejo, F., & García-López, S. (2009). A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World journal of gastroenterology, 15(37), 4638–4643.
  3. Bouri, S., & Martin, J. (2018). Investigation of iron deficiency anaemia . Clinical medicine (London, England), 18(3), 242–244.
  4. Cappellini, M., Musallam, K., & Taher, A. (2019). Iron deficiency anaemia revisited. Journal Of Internal Medicine, 287(2), 153-170.
  5. Food and Agriculture Organization of the United Nations. (2001). Human Vitamin and Mineral  Requirements (p. 195). Rome: Food and Nutrition Division. Retrieved from
  6. Stoltzfus, R., & L. Dreyfuss, M. Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anemia. United States of America: International Nutritional Anemia Consultative Group. Retrieved from
  7. Lopez, A., Cacoub, P., Macdougall, I., & Peyrin-Biroulet, L. (2016). Iron deficiency anaemia. The Lancet, 387(10021), 907-916.
  8. Miller J. L. (2013). Iron deficiency anemia: a common and curable disease. Cold Spring Harbor perspectives in medicine, 3(7), a011866.
  9. Muñoz, M., Villar, I., & García-Erce, J. A. (2009). An update on iron physiology. World journal of gastroenterology, 15(37), 4617–4626.
  10. Office of Dietary Supplements – Iron. (2021). Retrieved 12 September 2021, from
  11. Parasher, A. (2020). COVID-19: Current understanding of its Pathophysiology, Clinical presentation and Treatment. Postgraduate Medical Journal, 97(1147), 312-320.
  12. Wallace D. F. (2016). The Regulation of Iron Absorption and Homeostasis. The Clinical biochemist. Reviews, 37(2), 51–62.
  13. Warner, M., & Kamran, M. (2021). Iron Deficiency Anemia. Retrieved 12 September 2021, from
  14. Yuen, H., & Becker, W. (2021). Iron Toxicity. Retrieved 12 September 2021, from

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Sodium: The Role of this Vital Electrolyte and Mineral in the Body

January 18th, 2022
How to cite this article:

Baila BM, Latcu CM, Grewal VP. Sodium: The Role of this Vital Electrolyte and Mineral in the Body. 2022. Journal of Vita Columbia. 2(1).


Sodium is an essential nutrient involved in maintaining normal cellular homeostasis. Moreover, it plays an important role in controlling fluid and electrolyte balance, as well as  blood pressure. Sodium disorders, hyponatremia and hypernatremia, left untreated, endanger the lives of patients through their involvement in the pathogenesis of some of the main leading causes of mortality and morbidity worldwide, cardiovascular disease.


Sodium (Na) is both an electrolyte and mineral. It helps keep the water and electrolyte balance of the body. It also has a role in nerves and muscles’ function. [1] In body fluids, Na is found in the ionized form (Na +). Sodium is predominating in the extracellular sector where it is the main cation, while potassium is the main cation in the intracellular space. This asymmetric distribution of electrolytes on either side of the cell membrane requires active exchange via Na +/K +-ATPase. The preponderance of sodium over other cations is stored in other body fluids: gastric juice, pancreatic juice, gallbladder, intestinal juice, cecal fluid, sweat, CSF. A relatively large amount of sodium is found in the cartilage and slightly less in the bones. Sodium in the skeleton represents 15-30% of the total amount of the body, an amount of up to 15-30% of it can be exchanged with that of extracellular fluids. The total amount of sodium in the bones increases with age, while the mobilized fraction decreases. This fraction is clinically important in that it is a useful reservoir for sodium loss and acidosis. [2]

Metabolism of Sodium

Sodium metabolism is regulated by the kidney through the interaction of the renin-angiotensin-aldosterone system, sympathetic nervous system, atrial natriuretic peptide, brain natriuretic peptide, effective circulating volume, and serum H2O content. H2O metabolism is tightly regulated by arginine vasopressin. [3] Most of the sodium in the body (approximately 85%) is found in blood and lymphatic fluid, sodium levels of the body are partially controlled by a hormone called aldosterone, secreted by adrenal glands. Aldosterone levels transmit to the kidneys when retaining sodium in the body, instead of passing it in the urine. The balance of sodium between the three spaces is made through the separation membranes, by diffusion together with other substances (water, K, amino acids, etc.) and by active processes with various speeds. The total amount of Na in the body is 3,500-4,500mEq, found in two osmotically inactive forms: 500mEq in connective tissue, cartilage and 1,400-1900mEq in bones, skin tissue and adipose tissue.  Around 30% of Na is osmotically active and participates in the development of voltage-osmoregulatory processes. In the blood, Na circulates in two forms: bound and in an ionic state, chemically active. The value represents a biological constant with tight variation limits hyponatremia 136mEq and hypernatremia 160mEq. Exceeding these limits is accompanied by serious conditions such as “noncommunicable diseases including hypertension and cardiovascular disease” [20] that, untreated, could become life-threatening. [4]

Dietary Intake of Sodium

Sodium is an essential nutrient found in salt and many foods (mainly processed and ready-made ones). Our bodies need a small amount of sodium to be healthy, but too much can lead to high blood pressure, a major risk factor for cardiovascular disease (stroke, heart disease, etc) and kidney disease. Sodium intake has also been linked to an increased risk of osteoporosis, stomach cancer and severity of asthma. It is recommended (referred to as Adequate Intake-AI) that people over the age of one year consume between 1000-1500 mg sodium per day. People aged 14 and over should not eat more than 2300 mg sodium per day, based on the 2015–2020 U.S. Dietary Guidelines, referred to as the Tolerable Upper Intake Level (UL). An adult sodium intake above 2300 mg per day is likely to pose a health risk.[5][20]

Table 1: Recommended Daily Intake of Sodium [5]

Healthy Adequate Intake (AI)


Upper Limit (UL)


Infants 0-6 months 120 mg/day No data
Infants 7-12 months 370 mg/day No data
Children 1-3 years 1000 mg/day 1500 mg/day
Children 4-8 years 1200 mg/day 1900 mg/day
Teens 9-13 years 1500 mg/day 2200 mg/day
Adults 14-50 years 1500 mg/day 2300 mg/day
Older adults 51-70 years 1300 mg/day  
Older adults over 70 years 1200 mg/day  
Pregnancy 1500 mg/day  

The 2020-2025 Dietary Guidelines for Americans recommend that Americans consume less than 2,300 milligrams (mg) of sodium each day as part of a healthy eating pattern. [6] About 70% of the sodium consumed comes from processed, ready-made and restaurant foods, so only a small amount of sodium or salt is added to cooking and meals. [7] Based on data showing that 500,000 deaths each year are related to high blood pressure and that the risk of CVD increases by up to 6% for each 1 gram increase in sodium intake per day, reducing sodium intake becomes a priority in prevention of thousands of deaths annually. [8][20]

Diet Rich in Salt [19]

  • Mixed dishes including pizza, sandwiches, burgers, burritos, and tacos;
  • Processed meats such as bacon, sausage, lunch meats and hotdogs;
  • Bread and rolls or grains that include sauces or seasonings that include salt;
  • Canned vegetables and soups or frozen dinners;
  • Snacks including chips, pretzels, and crackers;
  • Condiments including salad dressings.

It is recommended to look after sodium quantities in particular foods by reading the Nutrition Facts label. People should choose foods with less than 120 milligrams of sodium per serving.

Restriction of sodium intake can be made by consuming a variety of fruits and vegetables regularly in the diet. For frozen products, people should look for ones without added sauces or sodium and if choosing canned vegetables, a selection of low-sodium or no-salt-added items is a good idea.  In addition to this, another way is to limit the intake of highly processed foods and avoid added salt in meals. [19]

Sodium Disorders


Hyponatremia is a low sodium concentration in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. [9,10]

Common Causes of hyponatremia include: 

  • Hypovolemic (GI, renal, skin, blood fluid loss);
  • Euvolemic (syndrome of inappropriate antidiuretic hormone secretion (SIADH)/stress, adrenal insufficiency, hypothyroid, diet/intake);
  • Hypervolemic (CHF, cirrhosis, nephrotic syndrome).[11]

Signs and Symptoms of Hyponatremia

Symptoms depend on the degree of hyponatremia and velocity of progression from the onset. If the onset is <24-48h is called acute hyponatremia and is more likely to be symptomatic, whereas chronic hyponatremia (>24-48 h) is less likely to be symptomatic due to adaptation. In other words, normalization of brain volume through loss of cellular electrolytes within hours and organic osmolytes within days. [11] Symptoms can be absent, mild, or severe. Mild symptoms include headaches, nausea, and balance issues.  Severe symptoms include confusion, seizures, and coma. [12][13]

Complications are seizures, coma, respiratory arrest, permanent brain damage, brainstem herniation, death. In case of rapid correction of hyponatremia, there is a risk of brain cell shrinkage which can develop osmotic demyelination of pontine and extrapontine neurons. Untreated can be irreversible such as central pontine myelinolysis. [11]

Treatment of Hyponatremia

In case of mild hyponatremia (no symptoms) the main treatment would be fluid restriction. However, the treatment in case of moderate to severe hyponatremia (confused, seizures) are saline infusion with loop diuretics, hypertonic (3 percent) saline, checking serum sodium frequently and ADH blockers (conivaptan, tolvaptan). Correction of serum sodium should be less than 10–12 mEq/L in the first 24 hours or less than 18 mEq/L in the first 48 hours. Otherwise, there is a high risk of central pontine myelinolysis. [14]


Hypernatremia is a common electrolyte problem that is defined as a rise in serum sodium concentration to a value exceeding 145 mmol/L. It is a frequently encountered electrolyte disturbance in the hospital setting, with unappreciated high mortality. Understanding hypernatremia requires a comprehension of body fluid compartments, as well as concepts of the preservation of normal body water balance. The human body maintains a normal osmolality between 280 and 295 mOsm/kg via Arginine Vasopressin (AVP), thirst, and the renal response to AVP; dysfunction of all three of these factors can cause hypernatremia. [15] Common causes are inadequate H2O intake (elderly/disabled) or inappropriate excretion of H2O, diuretics, Li, and diabetes insipidus.[11]

Signs and Symptoms of Hypernatremia

The major symptom is thirst. The most important signs result from brain cell shrinkage and include confusion, muscle twitching or spasms. With severe elevations, seizures and comas may occur. [16] Values above 180 mmol/L are associated with a high mortality rate, particularly in adults. [17]

Treatment of Hypernatremia

Treatment of hypernatremia is based on salt restriction and administration of normal saline until the patient is hemodynamically stable. When the vitals are stable, it is recommended the administration of half-normal saline. Correction of serum sodium should be less than 12 mmol/L in 24 h drop in Na+ (0.5 mmol/L/h) due to risk of cerebral edema, seizures, death otherwise. [11]


A balanced lifestyle, based on maintaining a healthy sodium intake, leads to an equilibrium that helps maintain homeostasis and the well-being of the cardiovascular system. Further studies would emphasize the relationship between the amount of sodium administered/consumed and the response in the body that would facilitate the approach to nutrition and management based on sodium.


  1. accessed in November 2021
  2. accessed in November 2021
  3. Samir Patel, James M. HunterJr., in Essence of Anesthesia Practice (Third Edition), 2011; 192
  4. Munteanu Constantin, Iliuţã Alexandru Rolul sodiului în organism, Balneo-Research Journal, 2011; Vol.2, Nr.2, 70-74
  5. accessed in November 2021
  1. U.S. Department of Agriculture, U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020–2025external icon, 9th ed. December 2020.
  2. Harnack LI, Cogswell ME, Shikany JM, Gardner CD, Gillespie C, Loria CM, et al. Sources of sodium in U.S. adults from 3 geographic regions external icon. Circulation. 2017;135(19):1775–83
  3. Palar K, Sturm R. Potential societal savings from reduced sodium consumption in the U.S. adult population external icon. Am J Health Promot. 2009;24(1):49–57
  4. Henry, DA (4 August 2015). “In The Clinic: Hyponatremia”. Annals of Internal Medicine. 163 (3): ITC1–19
  5. Chatterjee, Kanu; Anderson, Mark; Heistad, Donald; Kerber, Richard E. (2014). Manual of Heart Failure. JP Medical Ltd. p. 142
  6. Megan Drupals & Matthaeus Ware TORONTO NOTES 2021, 37th edition, Nephrology; 762-765
  7. Williams, DM; Gallagher, M; Handley, J; Stephens, JW (July 2016). “The clinical management of hyponatremia”. Postgraduate Medical Journal. 92 (1089): 407–11
  8. Williams, DM; Gallagher, M; Handley, J; Stephens, JW (July 2016). “The clinical management of hyponatremia”. Postgraduate Medical Journal. 92 (1089): 407–11
  9. Master the boards’ Step 3 Conrad Fisher, Nephrology; 654-655
  10. Saif A Muhsin, David B Mount Diagnosis and treatment of hypernatremia Best Pract Res Clin Endocrinol Metab 2016 Mar;30(2):189-203
  11. Lewis, J. L. (March 2013). “Hypernatremia”. Merck Manual of Diagnosis and Therapy. Medical Library Association.
  12. Ofran, Y.; Lavi, D.; Opher, D.; Weiss, T. A.; Elinav, E. (2004). “Fatal voluntary salt intake resulting in the highest ever documented sodium plasma level in adults (255 mmol L−1) a disorder linked to female gender and psychiatric disorders”. J. Intern. Med. 256 (6): 525–528.
  13. accessed in Nov 2021
  14. accessed in November 2021
  1. Wang YJ, Yeh TL, Shih MC, Tu YK, Chien KL. Dietary Sodium Intake and Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-Analysis. Nutrients. 2020;12(10):2934. Published 2020 Sep 25. doi:10.3390/nu12102934 

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Calcium: An Overview of Metabolism and Homeostasis

January 18th, 2022
How to cite this article:

Azer M and Azer M. Calcium: An Overview of Metabolism and Homeostasis. 2022. Journal of Vita Columbia. 2(1).


Calcium is a mineral found in nature but it is also very vital for processes essential for life in the human body. The human body can’t produce it so it must be ingested. The active form, free ionized calcium in the body must be kept within a strict range otherwise the body begins to enter a diseased state. Whether hypocalcaemia or hypercalcemia, the diseased state of the body presents with several vague signs and symptoms that can lead a physician on a wild goose chase if you aren’t aware of what to look for. In this essay we explore calcium and its effects on the body in normal and abnormal states.


The human body uses many minerals to regulate and help in its many physiological actions. Calcium is one of the most abundant minerals in the body. The word calcium is derived from the word ‘calas’ which means lime in Latin, because it was used by the ancient Romans to prepare lime (CaO) since the first century (2).

The human body contains around 1-1.3 kg of calcium, stored mainly in bones (approximately 99%) and the remaining 1% is distributed as follows: 15% bound to anions, 40% bound to albumin, 45% circulates as free ionized calcium (the active form) (6) .

Calcium is needed in many vital processes in the body; muscle contraction, nerve conduction, blood coagulation, maintenance of cell membranes and release of hormones to name a few uses (2) . A good accumulation of calcium in the bones at early stages in life is the best prevention of age-related bone loss and fractures.

It’s easy to say it is vital to essential processes in the body, and to prattle off a few titles but what exactly does calcium do? Calcium controls nerve excitability (2). The effect is mainly on the peripheral neuromuscular mechanism. It plays a role in maintenance of the integrity of the skeletal muscles (2). It is very essential for maintaining the tone and contractility of cardiac muscles (2). Calcium also takes part in the formation of certain tissue and bones (2).

Metabolism of Calcium

Despite the importance of calcium to the body, it doesn’t produce calcium. we depend on enteral absorption of calcium, around 1000 mg of calcium is ingested daily in a balanced diet. Around 400 mg of that is absorbed through the GIT and the rest is excreted with the stool.

Calcium bioavailability represents the amount of calcium that actually absorbed rather than the amount of calcium in the food (1).  To understand this better, we can use examples; as dairy foods have 30% bioavailability which means if the food label mentions that milk has 300 mg of calcium per cup, the body will absorb around 100 mg of it. On the other hand, leafy green vegetables may have less calcium content but have more bioavailability, for example bok choy has 160 mg of calcium per cup and a high bioavailability of around 50%, that means about 80 mg of calcium will reach the body. (1)

Here is a problem however, some plants have substances that bind to calcium and hence decrease calcium bioavailability such as (oxalates and phytates). Spinach has the largest amount of calcium in all vegetables (around 260 mg per cup) however it is rich in oxalates that bind with calcium making a compound that can’t be absorbed in the GIT. This results in a decrease of the bioavailability to around 5%, so out of the 260 mg of calcium, only 13 mg is absorbed.

The information is not to avoid vegetables since they are rich in many other nutrients, but to organize meals properly, especially if calcium supplements are used. i.e. don’t consume calcium binding food like spinach with calcium supplements or food rich in calcium. (1)

Other factors that affect calcium absorption include following a vegan diet, consuming a large amount of proteins or bowel and digestive diseases (inflammatory bowel disease, lactose intolerance, etc. (7)

Table 1: Recommended Daily Intake of Calcium by Age-Group (8)

Life Stage Recommended Amount
Birth to 6 months 200 mg
 Infants  7–12 months 260 mg
Children 1–3 years 700 mg
Children 4–8 years 1,000 mg
Children 9–13 years 1,300 mg
Teens 14–18 years 1,300 mg
Adults 19–50 years 1,000 mg
Adult men 51–70 years 1,000 mg
Adult women 51–70 years 1,200 mg
Adults 71 years and older 1,200 mg
Pregnant and breastfeeding teens 1,300 mg
Pregnant and breastfeeding adults 1,000 mg

Calcium Level Regulation

The average range of serum calcium is 2.2-2.6 mmol/L in adults. The normal level of ionized calcium 1.17-1.3 mmol/L. Calcium level in plasma depends directly on the balance of bone mineral deposition and resorption, intestinal absorption, and renal excretion (6) . The hormones responsible for regulating these processes include Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, and calcitonin (6).

PTH is secreted by the parathyroid glands as a response to hypocalcaemia, the gland senses the decrease in calcium serum level and secrete parathyroid hormone, the results of which are evident within minutes through:

  1. increase calcium reabsorption through the kidneys
  2. increase calcium absorption in GIT
  3. increase bone resorption
  4. stimulate activation of vitamin D to calcitriol which increases calcium absorption by the intestines. (4)

Vitamin D is produced in the skin by the help of ultraviolet rays from the sunlight. It is then activated to its major circulating form (25(OH) D) and hormonal form (1, 25(OH) 2D) in the liver and kidney, respectively. Its main role is to facilitate intestinal calcium absorption, it also plays a role in bone growth and remodeling by osteoblasts and osteoclasts. Vitamin D has other roles in the body, including reduction of inflammation as well as modulation of such processes as cell growth, neuromuscular and immune function, and glucose metabolism. (5)

Calcitonin is produced from the parafollicular cells in the thyroid gland. It decreases the serum calcium level through:

  1. increases cellular uptake
  2. increases renal excretion
  3. increases osteoblastic activity in bones to build more cells taking more calcium. (4)

In general, parathyroid hormone and vitamin D have a more active role on bone metabolism and remodeling than calcitonin.

Pharmacologic Interactions with Calcium Homeostasis:

There are also many medications affect the level of ionized calcium in blood stream:

There are drugs that increase ionized calcium levels, such as (6): 

  •       Calcium salts
  •       Hydralazine
  •       Lithium
  •       Thiazide diuretics
  •       Thyroxine

There are also drugs that decrease ionized calcium levels, such as (6): 

  •       Heparin
  •       Citrate
  •       Intravenous lipids
  •       Epinephrine
  •       Norepinephrine
  •       Isoproterenol
  •       Alcohol
  •       Ethylenediaminetetraacetic acid


Outside of the normal range of Calcium we are in one of 2 diseased states, either hypo- or hypercalcemia.

Calcium deficiency is usually due to an inadequate intake of it, therefore when the calcium level drops, the body borrows some from the bones, to be returned to the bones from calcium supplied through the diet (2). If there’s still an inadequate supply of calcium, there will not be enough calcium available to be returned to bones to maintain strong bones and total body health (2).

There are many situations that cause hypocalcaemia: (16)

  • Hypoparathyroidism
  • Pseudo hypoparathyroidism
  • Vitamin D deficiency
  • Renal tubular disease
  • Acute pancreatitis
  • Magnesium depletion (decreased secretion and tissue response to parathyroid hormone)
  • Hungry bone syndrome
  • Septic shock
  • Hyperphosphatemia
  • Massive blood transfusion (> 10 units)

Symptoms of Hypocalcemia

Perhaps two of the most common hypocalcaemia manifestations are perioral numbness or tingling and heart palpitations (arrhythmia). There are, however, a plethora of manifestations that are also quite non-specific but that altogether point us towards a veritable diagnosis.

Muscle Cramping, numbness and tingling in the arms and legs, hyperreflexia, dry Skin, brittle nails, coarse hair, repeated candida infections, cataract, increased PMS symptoms and joint pain are all non-specific on their own but altogether point to hypocalcaemia in the differential diagnosis (2). It is tetany (paresthesia of fingers, feet and perioral region, spasm of facial muscles, carpopedal spasm), heart palpitations (arrhythmia) and osteoporosis (i.e., bone fractures) that force us to investigate a lack of calcium in the body as the primary cause of disease.

There are also of course the famous signs to diagnose hypocalcaemia, Chvostek sign, twitching of facial muscle after tapping on facial nerve, anterior to exterior auditory meatus. Also, Trousseau sign, carpal spasm after inflating blood pressure cuff to 20mmhg above systolic for 3 minutes. (15)

Treatment of Hypocalcemia

Treatment for hypocalcaemia is relatively simple, there are many kinds of calcium supplements.

  • Calcium gluconate used to treat conditions caused by low  calcium  levels such as  osteoporosis, osteomalacia and rickets. It is also used in hypoparathyroidism. (9)
  • Calcium chloride for arrhythmia, hypermagnesemia, calcium channel blocker overdose and beta blocker overdose (10).
  • Calcium acetate to treat hyperphosphatemia in end stage renal failure (11).
  • Calcium citrate used for primary osteoporosis prevention it also protects against renal stones by oxalate chelating and prevent its absorption through the intestine (12).
  • Calcium carbonate, antacid (tums) (13)


When total serum calcium exceeds 10.4mg/dl ( 2.6 mmol/l ) or ionized calcium is more than 5.2 md/dl (1.3 mmol/l). (14)

Some of the more common causes of hypercalcemia are hyperparathyroidism, vitamin D toxicity, malignancy (paraneoplastic syndrome) in breast cancer, lymphoma, prostate cancer, thyroid cancer, lung cancer, myeloma, and colon cancer). Also, many other diseases can be associated with hypercalcemia such as tuberculosis, sarcoidosis, leprosy and histoplasmosis. (14)

Less commonly, diseases like milk alkali syndrome, familial hypocalciuric hypercalcemia and some conditions like immobility and severe dehydration can cause hypercalcemia. (14)

Symptoms of Hypercalcemia

What should we be on the search for in hypercalcemia? As in hypo, most of the signs and symptoms are vague and non-specific: nausea and vomiting, constipation, abdominal pain, generalized aches, polyuria, muscle weakness, depression, confusion, lethargy and coma. (14)

Hypercalcemia can also lead to kidney stones up to kidney failure. Other complications include osteoporosis, dementia and cardiac arrhythmia which can be fatal.

Treatment of Hypercalcemia

Management of hypercalcemia depends on the severity of each case and whether it’s acute or chronic. Usually it starts with IV saline and diuretics (furosemide). The next step is bisphosphonates. Also hemodialysis or surgical removal of parathyroid glands can be used for refractory cases. (14)


Calcium is one of the most important minerals in the body, it is essential and vital for life. However it has to be within a specified range as too much or too little of the active form in the blood can be disastrous and possibly fatal. While most of the signs and symptoms of calcium imbalance in the body are vague there are specific warning signs to be on the lookout for as physicians and special tests to determine if calcium imbalance is the culprit.


  1. Calcium – The Nutrition Source., Harvard T.H. Chan – School of Public Health.,
  2. Piste,Pravina., Calcium and its Role in Human Body.,, January 2012.,
  3. Watson, Stephanie., Calcium: What you should know., WebMD -Vitamins and Supplements., June 2020.,
  4.  Lewis III, James L., Overview of Disorders of Calcium Concentration., Merck Manual – Professional Version., April 2020.,
  5. Vitamin D – Health Professional Fact Sheet., National Institutes of Health- Office of Dietary Supplements., August 2021.,
  6. Goldberg, Deborah., Calcium, Ionized., Medscape – Laboratory Medicine., Nov. 2019.,
  7. Mayo Clinic Staff., Calcium and calcium supplements: Achieving the right balance., Healthy Lifestyle – Nutrition and Healthy Eating., November 2020.,
  8. Calcium – Fact Sheet for Consumers., National Institutes of Health – Office of Dietary Supplements. March 2021.,
  10. Calcium Chloride (Rx) – Brand and other names., Medscape – Drug and Diseases.,
  11. Calcium Acetate (Rx) – Brand and other names., Medscape – Drug and Diseases.,
  12. Calcium Citrate (Rx) – Brand and other names., Medscape – Drug and Diseases.,
  13. Calcium Carbonate (Rx) – Brand and other names., Medscape – Drug and Diseases.,
  14. Lewis III, James L., Hypercalcemia. MSD Manual Professional version. April 2020.,

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Vitamin B6: A Synopsis of this Critical Micronutrient

January 18th, 2022
How to cite this article:

Latcu CM, Baila BM, Grewal VP. Vitamin B6: A Synopsis of this Critical Micronutrient. 2022. Journal of Vita Columbia. 2(1).


Vitamin B6, first discovered as a factor that cured dermatitis in rats, is a water-soluble vitamin that works as a coenzyme for more than 100 essential enzyme-catalyzed reactions. It is rapidly metabolized and excreted. Therefore it is very unlikely that vitamin B6 deficiency or toxicity happens. In case of toxicity nerve damage-related symptoms and other symptoms can occur. Its most biologically active form, PLP – pyridoxal 5’-phosphate form, and its dependent enzymes play an important role in cellular metabolism and other important reactions. Finally, vitamin B6 is catabolized through the oxidation of pyridoxal to 4-pyridoxic acid, which is excreted in the urine. Besides all these general characteristics of this vitamin, studies also outline new insights into its impact on human health and the use of vitamin B6 supplements.


Vitamin B6 (Vit. B6), also called pyridoxine, part of the group of vitamin B complex, water-soluble, chemically quite distinct compounds, is a really important compound for overall cellular metabolism being involved in amino acid biosynthesis and degradation, also in glucose and fatty acid metabolism. [1]

Vit. B6 consists of a group of six related vitamers: pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM) and the 5′-phosphates (PLP- pyridoxal 5’-phosphate, PNP- pyridoxine 5’-phosphate and PMP – pyridoxamine-5’-phosphate). The animal tissues contain mainly the PLP and PMP forms, and plant-based products the PN and PNP forms. Humans have 4-pyridoxic acid (4-PA) as their main excretory form. PN, PL and PM forms are mainly converted to PLP via some consecutive reactions that require a kinase (whose role is to phosphorylate the 5′hydroxymethyl group) and the pyridoxamine phosphate oxidase – PNPO (whose role is to phosphorylate the PNP and the PMP). The PLP is the biologically active form of vitamin B6.  [2][4]

Metabolism of Vitamin B6

Absorption & Transportation

Humans and animals cannot synthesize vit. B6, hence they rely on external sources. [2] The absorption, through passive diffusion, takes place in the intestine and is divided into two parts: dietary ingestion that takes place in the small intestine (jejunum) and the uptake of bacteria produced vit. B6 that takes place in the large intestine. [3][9] The intestine absorbs only the nonphosphorylated B6 vitamers and, in the intracellular compartment of the intestine, most of them go to the liver and are converted to phosphorylated forms (PL to PLP by PL kinase for instance). [2][7][9] Absorption also requires phosphatase-mediated hydrolysis followed by transport of the nonphosphorylated form into the mucosal cell, regardless of dose. [2] PLP must be bound to serum albumin (ALB) as a Schiff base form and be delivered entirely from the liver as a PLP-albumin complex, which protects PLP from hydrolysis. [2][7][8][9] After these steps, the PLP-albumin complex requires dephosphorylation (by an alkaline phosphatase) to pyridoxal (less hydrophilic form) before being secreted into the circulatory blood system for delivery to the different tissues and organs, and even crossing the blood-brain barrier (BBB). [7][8] After the liver, the choroid plexus seems to be the only organ able to readily release PLP, which explains the relatively high percentage of PLP in cerebrospinal fluid. [7] After all these reactions, the B6 vitamers must be rephosphorylated by pyridoxal kinase in the brains cells and in other target cells too, found mostly in the mitochondria and the cytosol (where quite similar mechanisms occur). [2][7] 

There is also a „salvage pathway” [7] for PLP formation from other forms such as PNP and PMP by oxidation by PNP oxidase. [2] PMP form is also generated from PLP via aminotransferase reactions. [2] PLP capacity of binding limits the accumulation in tissues and organs at high intakes of vit. B6. [2] If this capacity is exceeded, free PLP is rapidly hydrolyzed and nonphosphorylated forms of vit. B6 are released by the liver and other tissues into circulation. [2] At pharmacological doses of B6, the high capacities for PLP-protein binding of muscle, plasma, and erythrocytes (hemoglobin) allow them to accumulate very high levels of PLP when other tissues are saturated.[2]


B6 vitamers are excreted mainly in the urine, but also in feces. [2][7][9] When the intakes exceed the requirements, dephosphorylation of the pyridoxal phosphate takes part (mainly in the liver) and this is oxidized to the bioactive catabolite 4- pyridoxic acid (PA) – the main excretory product – and other forms or could also be excreted unchanged in urine [2][7][9]

Functions of Vitamin B6:

Based on several studies vit. B6, in the form of pyridoxal 5’-phosphate (PLP), functions as a coenzyme for more than 100 essential enzymes-catalyzed reactions, mostly in amino acid, fat, and glucose metabolism [2][3] The biggest part of PLP in the body is found in muscle, bound to phosphorylase, up to 80% of the body’s stores – around 1,000 μmol or 167 mg. [2] The carbonyl group of PLP binds to proteins via a Schiff base. [2][4] The process begins by forming a Schiff base between a received amino acid, via its α-amino group, and the carbonyl group of PLP. [2][4] Thus, PLP is covalently linked to the active sites of aminotransferases, decarboxylases, racemases and dehydrases, among other enzymes. [2][4] The PLP-dependent enzymes are involved in lots of reactions, such as:

  •  amino-acid metabolism – co-catalyzing transamination, racemization, decarboxylation and α,β-elimination reactions; [3]
  •  fatty acid metabolism – catalysis of the synthesis of essential polyunsaturated fatty acids by the desaturation of linolic acid and γ-linolenic acid; [3]
  •  gluconeogenesis – cofactor for the transamination reactions and the degradation of storage carbohydrates, such as glycogen – glycogen phosphorylase (PLP-enzyme dependent) mediates the glycogen breakdown by the release of glucose from glycogen;[3][5]
  • nervous system – neurotransmitters biosynthesis (epinephrine, serotonin, taurine, dopamine, norepinephrine, histamine, and γ-aminobutyric acid) and its precursor formation (niacin formation – conversion of tryptophan to niacin); [5][8]
  •  erythrocyte functions – the first step of heme biosynthesis – in humans, mammals, birds;[2][3][5]
  • chlorophyll biosynthesis –  in plants; [3]
  • phytohormone ethylene biosynthesis – in plants; [3]
  • oxidative stress  reduction – protects cells from oxidative stress by exhibiting antioxidant activity that can exceed that of vitamins C and E and low vitamin B6 level may lead to oxidative DNA alteration; [3][6]
  •  immune system – hormone modulation and one-carbon metabolism – involved in transsulfuration pathway from homocysteine to cysteine and tryptophan degradation (to kynurenine and then to cytotoxic 3-hydroxykynurenine – via kynurenine pathway) – its alternation can affect the nucleic acid synthesis, lymphocyte production and antibody response to antigens. [2][3][5][9]

Vitamin B6 Deficiency:

Vitamin Blevel was associated with different health issues ever since its first mention formula in 1932, by S. Ohdake, a Japanese scientist, when it was called “rat pellagra prevention factor” [3].[1] Clinical manifestations of deficiency and toxicity are less common due to its quick metabolization and excretion. [16] Usually, it has insignificant symptoms toxicity and deficiency-related, but when very high levels are administered or the intakes are inadequate, it can damage the nerves and also a significant part of the population could have inadequate levels of vitamin B6, despite apparently adequate levels of intake. [16]

Vitamin B6 and Skin Conditions:

Vitamin Bis known for its important role in skin development and maintenance. [3] Even from the beginning of its research, some scientists investigated a “rat pellagra prevention factor” [3] that could cure a pellagra-like skin disorder in rats, called acrodynia.[3] They used a special yeast-based diet and noticed that acrodynia has been cured. [3] Although subsequent studies did not confirm the initial assumption that PN therapy could be beneficial in atopic dermatitis, other studies showed that prolonged exposure to vitamin Bcould be associated with dermatitis and increased photosensitivity in humans and cell cultures. [3][10] In other studies, despite its phototoxic effects, vit. Bis thought to have a protective effect against photosensitivity in some microorganisms. [3][10] Furthermore vit. Bsupplements might also inhibit the growth of melanomas in vivo and in vitro studies. [3][10]

Vitamin B6 and Chronic Disease / Cognitive Functions:

By its role in such a variety of metabolic reactions, including homocysteine degradation and serotonin biosynthesis, vit. Bexerts lots of functions in the human body and has been associated with cancer, cardiovascular events, seizures, migraine, chronic pain, depression, cognitive failure, immune deficiency, irritable bowel syndrome, etc. [11]

Low PLP levels associated with hyperhomocysteinemia could have a role in cardiovascular disease. [2] Hyperhomocysteinemia is known for its roles as a cardiovascular risk factor (in atherosclerosis and congenital heart diseases), being a predictor of primary-cause vascular mortality and associated with mental retardation, seizures, depression, schizophrenia, and cognitive impairment. [2][8][16]

Low PLP levels were also associated with high levels of plasma C-reactive protein (CRP), an important inflammatory marker involved also in atherosclerosis pathogenesis. [6] This association between PLP levels and CRP plasma level supports the affirmation that inflammation has a significant role in linking low vit. B6 level and cardiovascular risk. [6] Another explanation of this affirmation could be the involvement of vit. B6 in the biosynthesis of the nucleic acids and mRNA and protein synthesis, consequently in the production of cytokines and inflammatory mediators during the inflammatory response that might increase the use of PLP. [6]

Vitamin B6’s role in diabetes mellitus can be explained by its benefits in endothelial dysfunction improvement, a factor involved in the arteriosclerosis progression and nephropathy related to this pathology. Vit. B6 can also have a „positive impact” [1] in diabetic nephropathy by preventing oxidative stress products formation and endothelial dysfunction improvement respectively. [1]

Vitamin B6’s role in serotonin metabolism may explain the correlation between vit. B6’s intake and its benefits related to inflammatory bowel syndrome symptoms. [11]

Inborn errors of metabolism that occur from genetic mutations in encoding PLP-dependent enzymes such as X-linked sideroblastic anemia, xanthurenic aciduria, primary hyperoxaluria type 1, cystathionuria, homocystinuria, gyrate atrophy, aromatic L-amino acid decarboxylase deficiency and pyridoxine-dependent epilepsy resulting from α-aminoadipic-semialdehyde dehydrogenase mutations, can benefit of PN therapy. Another inborn error of metabolism, pyridoxamine phosphate oxidase (PNPO) deficiency, affects the conversion of PN to PLP and leads to PLP deficiency, consequently to low PLP concentrations in cerebrospinal fluid, and epileptic encephalopathy in newborns. It was mentioned a clinical improvement in cases of early intravenous supplementation with PLP in PNPO deficiency. [4]

Vitamin B6 and other Clinical Correlations:

Some of the health issues associated with dietary levels of vit. B6 and their treatment efficacy are not very well known but some studies established some correlations between these:

  • some scientists discovered several connections between high doses of vit. B6 and tumour growth reduction that may occur by suppressing cell proliferation and angiogenesis – research made mainly on cell cultures and mice; [1]
  • normal vit. B6 levels may have a role in the pathogenesis of asthma or carpal tunnel syndrome; [1]
  • vitamin B6 also might help women with symptoms associated with premenstrual syndrome (fatigue, nervousness, irritability, emotional disturbance, headache, fluid retention, depression, etc.). [1][16]

Vitamin B6 Toxicity:

Higher doses of vitamin B6 can be neurotoxic (as well as low doses). [4][5][12] The side effects of the high doses were related especially to PN intake and self-medication, but there is not clear yet what dose is safe to prevent toxicity and subsequent studies are needed. [4] It is thought that the duration of supplementation, genetic background, diet and medication use (dose of vit. B6, co-medication and so on) together play an important role in someone’s reaction to vitamin B6’s vitamers related side effects. [15] Neurologic, dermatologic and other side effects were identified: peripheral neuropathy associated with limb hypo-/areflexia and ataxia, sensory nerve damage associated with impaired limb touch sensation and tingling sensation, vesicular dermatosis and photosensitivity on sun-exposed skin regions, aggravated acne lesions, dizziness, nausea and breast tenderness. [4] [5][12]

Drug Interactions with Vitamin B6:

The treatment of some diseases and some conditions (inflammation) might affect the vit. B6 levels. These interactions result in the need for adjustment of the doses when are used together: phenytoin, phenobarbital, isoniazid, theophylline, MAO inhibitors, amiodarone, hydralazine, levodopa, low-dose of oral contraceptive, alcohol, antibiotics (cycloserine), penicillamine.[4][5][14][16] All these interactions affect, mainly, the central nervous system and the skin, but more studies are needed to explore in detail how exactly these factors affect plasma vitamin B6 level and if they create frank deficiency. [4][5][12][16]

Dietary Intake:

Table 1. Vitamin B6 Recommended Daily Intake (RDI) reference values [12][13]

Vitamin B6 (mg/day)
Infants Females
0-6 months: 0.1 mg 14-18 years: 1.2 mg
7-12 months: 0.3 mg 19-50 years: 1.3 mg
Children 51 years and older: 1.5 mg
1-3 years: 0.5 mg Pregnant Women
4-8 years: 0.6 mg 1.9 mg
9-13 years: 1.0 mg Nursing Women/Lactation
Males 2.0 mg
14-50 years: 1.3 mg  
51 years and older: 1.7 mg  

Dietary Sources:

Vitamin B6 is found within natural sources mainly as PLP and PNP (primary dietary forms) and plant-based sources contain mainly high amounts of glycosylated PN (with lower bioavailability which requires hydrolyzation to PN). [4] Its bioavailability is estimated at around 75% from a varied diet. [4]

Table 2. Rich sources of vitamin B6 [12]

Food Serving size Vitamin B6 content

(milligrams [mg])

% Daily Value
Chickpeas, canned 1 cup


Beef liver, pan-fried 3 ounces 0.9 45
Yellowfin tuna, cooked 3 ounces 0.9 45
Sockeye salmon, cooked 3 ounces 0.6 30
Chicken breast, roasted 3 ounces 0.5 25
Fortified breakfast cereal 1 serving 0.5 25
Potatoes, boiled 1 cup 0.4 20
Turkey, roasted 3 ounces 0.4 20
Banana 1 medium 0.4 20
Marinara sauce 1 cup 0.4 20
Ground beef patty, broiled 3 ounces 0.3 15
Waffles, toasted 1 waffle 0.3 15
Bulgur, cooked 1 cup 0.2 10
Cottage cheese, 1% low-fat 1 cup 0.2 10
Winter squash, baked ½ cup 0.2 10
Long-grain white rice 1 cup 0.1 5
Mixed nuts 1 ounce 0.1 5
Seedless raisins ½ cup 0.1 5
Onions, chopped ½ cup 0.1 5
Spinach, boiled ½ cup 0.1 5

There are some additional good sources of vitamin B6: torula yeast, brewer’s yeast, egg yolks, sunflower seeds, wheat germ, soybeans, walnuts, lentils, lima beans, buckwheat flour, bananas, avocados and other noncitrus fruits. [4][12]

Pharmacological Uses of Vitamin B6:

A series of studies were performed to identify the beneficial effects of vitamin B6 in the treatment of different conditions and their symptoms. Despite all its benefits, studies revealed that vitamin B6 has some of the benefits, indeed, but not always are truly effective:

  •  morning sickness (pregnancy-related or radio/chemotherapy-related nausea) – between 50 and 200 mg vit. B6 has an antiemetic effect and may help. [12][16] Also, FDA (U.S. Food and Drug Administration) approved doxylamine-pyridoxine therapy, in 2014, for the treatment of pregnancy-related nausea and vomiting; [4]
  • carpal tunnel syndrome – although there is evidence that vitamin B6 might have some beneficial effects, there is no scientific and clinical evidence that it is truly effective in treating it; [12][16] 
  •  premenstrual syndrome – vitamin B6 may have some beneficial effects in controlling the side effects related symptoms due to high dose of oral contraceptives and also the premenstrual syndrome symptoms such as nervousness, irritability, emotional disturbance, headache and depression but there is no evidence that women who experience the premenstrual syndrome have lower vitamin B6 levels. [16] Thus there are not enough pieces of evidence of this efficacy, supplements of vitamin B6 are still used (prescribed or self-administered) for premenstrual syndrome symptoms relief; [12][16] 
  • hyperhomocysteinemia –  it is thought that higher intakes of vitamin B6 (more than what is considered normal)  could have a beneficial impact on reducing plasma homocysteine levels in hyperhomocysteinemia patients, but it seems the evidence is insignificant;[12][16]
  •  tardive dyskinesia –  during a study, within vitamin B6 was administered, was identified that this may help to improve the symptoms related to tardive dyskinesia and be more effective where it was administered than within the studied placebo groups; [12]
  • hypertension –  vitamin B6 supplements of 5 mg/kg body weight/ day may have beneficial effects on reducing blood pressure in patients diagnosed with essential hypertension; [16]
  •  inborn errors of metabolism that occurs from genetic mutations in encoding PLP-dependent enzymes – vitamin B6 supplements of 200–1000 mg/day are beneficial and requires life-long administration; [4][16]
  • asthma, depression, diabetes of pregnancy, HIV infection, photosensitivity, preventing kidney stones formation, schizophrenia, seborrheic dermatitis, antipsychotic sides effects, vertigo, acute alcohol intoxication, atopic dermatitis, autism, diabetic peripheral neuropathy, Down’s syndrome, Huntington’s chorea – overall, there is little or no evidence or contradictory information from clinical trials that vitamin B6 might be effective in the treatment of these conditions. [12][16]


Lately, the biosynthesis of vitamin B6 and its functional and metabolic characteristics as a coenzyme have been well studied and the information discovered has been confirmed or refuted by subsequent studies. The diversity of the most biologically active form of vitamin B6, the PLP form, implicated in a wide range of enzymatic reactions, is an indicator of the major importance of this vitamin and indicates several possible targets for future therapeutic approaches. Further studies are needed on the exact mechanism of how vitamin B6 may be more beneficial and needed in certain populations and conditions. Overall, with all the knowledge about the functional properties of vitamin B6 in different physiological and nutritional conditions, human health and well-being can benefit from them and this topic could also become part of the most challenging studies in the future. 


  1.     Hellmann H., Mooney S. Vitamin B6: A molecule for human health? Mol. Basel Switz. 2010;15:442–459. https://doi:10.3390/molecules15010442;
  2.     Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US); 1998. 7, Vitamin B6. Available from:;
  3.     Mooney, S.; Leuendorf, J.-E.; Hendrickson, C.; Hellmann, H. Vitamin B6: A Long Known Compound of Surprising Complexity. Molecules 2009, 14, 329-351.;
  4.     Patrick J Stover, Martha S Field, Vitamin B-6, Advances in Nutrition, Volume 6, Issue 1, January 2015, Pages 132–133,;
  5.     Robert B. Rucker, John W. Suttie, Donald B. McCormick, Lawrence J. Machlin. Handbook of Vitamins, third edition, revised and expanded, 2001;339-396;
  6.     Jian Shen, Chao-Qiang Lai, Josiemer Mattei, Jose M Ordovas, Katherine L Tucker, Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study, The American Journal of Clinical Nutrition, Volume 91, Issue 2, February 2010, Pages 337–342,;
  7.     Matthew P. Wilson, Barbara Plecko, Philippa B. Mills, Peter T. Cl, Disorders affecting vitamin B6 metabolism, The Journal of inherited metabolic disease, Volume 42, Issue4, July 2019, Pages 629-646,;
  8.     Parra, M.; Stahl, S.; Hellmann, H. Vitamin B6 and Its Role in Cell Metabolism and Physiology. Cells2018, 7, 84.;
  9.     Minovic, I. (2018). Assessment and clinical implications of functional vitamin B6 deficiency. Rijksuniversiteit Groningen;
  10. Stephen P. Coburn, Andrzej Slominski, J. Dennis Mahuren, Jacobo Wortsman, Lovisa Hessle, Jose Luis Millan, Cutaneous Metabolism of Vitamin B-6, Journal of Investigative Dermatology, Volume 120, Issue 2, 2003, Pages 292-300, ISSN 0022-202X,;
  11. Kjeldby, I.K., Fosnes, G.S., Ligaarden, S.C. et al. Vitamin B6 deficiency and diseases in elderly people – a study in nursing homes.BMC Geriatr 13, 13 (2013).;
  12. Health Information – Vitamin B6. Pierremont Endrocrine Center website. Available at: Accessed on November 11, 2021;
  13. Dietary Reference Intakes – Available at: Accessed on November 11, 2021;
  14. Pyridoxine (Vitamin B6) – Available at Accessed in November 11, 2021;
  15. Misha F Vrolijk, Geja J Hageman, Sonja van de Koppel, Florence van Hunsel, Aalt Bast, Inter-individual differences in pharmacokinetics of vitamin B6: A possible explanation of different sensitivity to its neuropathic effects, PharmaNutrition, Volume 12, 2020, 100188, ISSN 2213-4344,;
  16. Bender, D. (1999). Non-nutritional uses of vitamin B6. British Journal of Nutrition, 81(1), 7-20. doi:10.1017/S0007114599000082.

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Vitamin B1: An Overview of Thiamine Deficiency (the anti-beriberi factor)

January 18th, 2022
How to cite this article:

Azer M, Azer M, Magsakay CR. Vitamin B1: An Overview of Thiamine Deficiency (the anti-beriberi factor). 2022. Journal of Vita Columbia. 2(1).


Beriberi, or hypovitaminosis B1, is a thiamine deficiency characterized by one of 3 states, either dry (neurological), wet (cardiovascular) or infantile beriberi. Thiamine, vitamin B1, is the second essential vitamin to be discovered. Thiamine can’t be stored in the body, so it must be ingested regularly in order to stay healthy and fit. In different groups of people, vitamin B1 was found out to be low in levels, whether in the poor who can’t afford a variety of foods, or in the rich who eat highly specialized foods, or even those out in the open sea with only enough food for a limited period. It will take some time for one to reach a state of Beriberi and the solution is just simple, supplement with thiamine. In fact, as long as you haven’t gotten to the stage where you manifest with neurological deficits, you still may have a good prognosis.


Beriberi, a disease prevalent in South Asia in the last few centuries. It was a mysterious condition with a wide variety of symptoms ranging from weight loss, paralysis, nerve dysfunction up to brain damage and death. The word “beri” means ‘weak’ or ‘I can’t’ in Sinhalese – the Sri Lankan native tongue. (1)

By the late 19th century, it was considered a serious problem among the Japanese sailors, being so mysterious, it was believed to be a kind of infectious disease. Dr. Takaki Kanehiro, however, after an exhaustive study of the cause of this strange disease and through keen observation, managed to link it to the poor diet of Japanese sailors, which consisted solely of rice. (1)

A few years later, a Dutch physician – Dr. Christian Eijkman, noticed that beriberi is more common among rich people in Europe rather than poor communities. He suspected that the reason for this is the high quality polished rice that was only affordable for the wealthier families, whereas the poorer farmers usually eat unpolished rice with the kernel and husk intact. (1)

An experiment was made on chickens to prove this point, it showed that chicken which was offered polished rice showed symptoms of beriberi and recovered when offered unpolished rice. (1)

In 1912 a chemist named Casimir Funk managed to isolate the anti-beriberi factor from the brown rice and called it “Vitamin” which means ‘an amine vital for life’. Later, this anti-beriberi compound was named “Thiamine” which means ‘a sulfur containing amine’. Vitamin A was already discovered so Thiamine was called vitamin B1 (1).

What is Vitamin B1 (Thiamine)?

So what is Thiamine? Simply put, Thiamine is a water soluble vitamin which acts as a coenzyme and has an important role in carbohydrate metabolism (2). It also plays a vital role in transferring nerve impulse and in myelin sheath stability (5). The human body can’t produce thiamine and can only store around 30 mg of it in the body, so it must be eaten in food. Its absorption occurs in the small intestine, specifically in the jejunum (2). Vitamin B1 exists in whole grain foods, green leafy vegetables, milk products, nuts, pork, fish, eggs and beef (2). However, there are foods that contain Thiaminase, an enzyme that breaks down Thiamine, which are found in shellfish, tea and coffee (2).

Vitamin B1 (Thiamine) Deficiency

There are 3 primary causes for thiamine deficiency:

  1. Decreased supply
    – rice-dependent diet
    – malnutrition
    – parenteral nutrition
    – alcoholism
    – post-bariatric surgery
  2. Increased demand
    – hyperthyroidism
    – pregnancy & lactation
    – septic shock
  3. Thiamine loss
    – diarrhea
    – diuretics
    – hyperemesis gravidarum
    – severe burns
    – hemodialysis 

Thiamine deficiency has 3 major presentations: Dry Beriberi (neurologic symptoms), Wet Beriberi (cardiovascular symptoms), and Infantile Beriberi.

A. Dry Beriberi (neurologic symptoms)

It happens due to myelin sheath degeneration without ongoing inflammation and may manifest as follows:

  • Sleep disturbance
  • Poor memory
  • Muscle cramps
  • Peripheral neuropathy
  • Bilateral symmetrical sensory and motor deficits in lower limbs
  • Absent knee and ankle reflexes
  • Muscle atrophy
  • Foot drop

In western countries, a severe variation of dry beriberi called Wernicke’s Encephalopathy (WE) is more common especially among people with chronic alcoholism, as around 80% of people with chronic alcoholism develop thiamine deficiency. This is because ethanol consumption decreases the absorption of thiamine in the gastrointestinal tract which affects thiamine stores in the liver impairing thiamine phosphorylation. (2,4)

In WE, ocular manifestations are most prominent specifically nystagmus, lateral rectus and conjugate gaze palsies due to oculomotor and abducent nuclei involvement.

Wernicke’s Encephalopathy is manifested by: (4)

  • Confusion or agitation.
  • Gait disturbance due to cerebellar impairment.
  • Polyneuropathy and vestibular nucleus involvement.
  • Hypothermia (as thiamine deficiency may impair the temperature regulating part in the brain)

Korasakoff is a late, more severe presentation of Wernicke Encephalopathy which is characterized by retrograde and anterograde amnesia with confabulation. It usually starts with gastrointestinal symptoms such as nausea, vomiting, and abdominal pain. These symptoms are usually followed by fever, ataxia, nystagmus, ocular nerve palsy with progressive mental impairment. Eventually Korsakoff Syndrome develops as memory is affected and psychosis develops. Once Korsakoff Syndrome develops the chances of improving or returning to a state of well-being diminish significantly. (2,4,5)

B. Wet Beriberi (cardiovascular symptoms)

Widespread peripheral vasodilation leads to hypotension and activation of the renin-angiotensin-aldosterone system resulting in salt and water retention and volume overload, this eventually results in high output congestive heart failure. (2)

Cardiac symptoms may manifest as: (2)

  • Chest pain due to myocardial injury as a response to work overload on the heart (overuse injury)
  • Hypotension
  • Tachycardia
  • Lower limb edema

Acute fulminant form of cardiovascular beriberi called “Shoshin beriberi”. It is a rapid severe form of wet beriberi where the heart is affected tremendously trying to meet high body demands. Aside from edema, the patient may suffer from cyanosis, tachycardia, distended neck veins and restlessness. In this stage, cardiac support is a critical part of treatment along with thiamine supplementation. This avoids the sudden vasoconstriction which may happen before the cardiac muscle recovery and may result in low output heart failure. (2)

B. Infantile Beriberi (2)

This happens in infants who are exclusively breastfed by a mother who is thiamine deficient.

The symptoms may include:

  • Absent reflexes
  • Aphonia
  • Vomiting
  • Agitation
  • Nystagmus
  • Grunting
  • Convulsions
  • Congestive heart failure

Diagnosis of Vitamin B1 (Thiamine) Deficiency:

In most cases, thiamine administration is the most practical test, if the patient responded to the treatment, then it confirms the diagnosis. If lab testing is needed, thiamine blood level is measured. The test of choice, however, is the thiamine loading test which is the best indicator of thiamine deficiency. A rise of 15% or more in enzyme activity is positive for thiamine deficiency; however, this test is time consuming and expensive that is why it is rarely used in daily practice.

Treatment of Vitamin B1 (Thiamine) Deficiency:

The WHO recommends that in case of mild thiamine deficiency, 10 mg of thiamine daily for a week should be taken then 3-5 mg daily for 6 weeks. If it is a severe form, 25-30 mg IV is given in infants and 50-100 mg IV in adults then followed by 10 mg IM daily for a week. After which, it is followed by 3-5 mg daily for at least 6 weeks. (6)

The prognosis? Despite the severity of symptoms and that beriberi can be quickly fatal, it’s easily treatable and most of the symptoms resolve with thiamine supplements. Cardiac symptoms are the best to respond to treatment, it resolves in around 24 hours of treatment. Dry beriberi symptoms may improve however once Korsakoff syndrome is developed, minimal improvement is expected. (2)


  1. May, Paul. “Molecule of the Month – Vitamin B1 (thiamine) deficiency of this causing Beriberi”, Bristol university. September 2017.
  2. Nguyen-Khoa, Dieu-Thu., Beriberi ( Thiamine Deficiency ). Medscape free article.University of California. 2020 Mar.
  3. Polegato, BF., Pereira, AG.,  Azevedo, PS., Costa, NA., Zornoff, LAM., Paiva, SAR., Minicucci, MF., Role of Thiamine in Health and Disease. Nutr Clin Pract. 2019. 34(4):558-564.  DOI: 10.1002/ncp.10234. Epub 2019 Jan 15. PMID: 30644592.
  4. Salen, Philip N., Wernicke encephalopathy, Medscape free article. 2018 Nov.
  5. Wiley, Kimberly D. and Gupta, Mohit. Vitamin B1 Thiamine Deficiency. NCBI-NIH . June 21 2021.

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Vitamin C: An Overview – Metabolism, Toxicity, Deficiency, Involvement

January 17th, 2022
Blessy K Joy, MBBS
Kevin Joy, BSc, DCh
Wafaa Chorfi, MD
How to cite this article:

Joy BK, Joy K, Chorfi W. Vitamin C: Metabolism, Toxicity, Deficiency, Involvement. 2022. Journal of Vita Columbia. 2(1).


This is a brief overview on the on water soluble molecule known as ascorbic acid, more commonly referred to as vitamin C. The following article will overview the sources of vitamin C, the appropriate dosing, metabolism, and the consequences of vitamin C toxicity and deficiency, while examining the impact it has normal physiology and its role as a therapeutic in treating certain ailments.


Vitamin C is a water-soluble molecule that is required to help support normal physiological functions within the body [1]. This vitamin acts as a reducing agent and provides some antioxidant properties which may help in preventing tissue damage. Also known as ascorbic acid, vitamin C can be sourced readily from common dietary sources or in the form of supplements [2]. Appropriate dosing and adequate daily intake are required to help normal bodily functions such as collagen synthesis [1,2]. While there is no gold standard to measure levels of vitamin C in the body, examining plasma levels are sufficient to determine whether hypo or hypervitaminosis C exists [7,8]. Vitamin C also plays supportive roles in physiology and as an adjunct therapeutic in numerous pathologies. All of this will be explored further in this brief overview.

Dietary Intake of Vitamin C

As Vitamin C cannot be synthesized endogenously, exogenous sources of Vitamin C are required to maintain normal levels within the body [1]. Natural food sources are the primary exogenous source for humans to obtain vitamin C. Foods such as citrus fruits, tomatoes and tomato juices, and potatoes are major sources of Vitamin C, especially in North America [3]. For reference, consuming a medium size orange provides roughly 70mg of vitamin C [4]. Some other sources of vitamin C includes fruits such as strawberries, kiwis, and cantaloupe, in addition to vegetables like green and red peppers, broccoli, spinach, cabbage, and Brussel sprouts [3,4]. Where absent, such as in grains, vitamin C can be added to foods, like cereals, in order to fortify them. Breast milk has also been found to contain vitamin C. When storing or preparing foods with vitamin C, the amount present within foods can be diminished with prolonged storage or high temperatures. Heat can destroy vitamin C, as such moderate temperature cooking such as with a microwave or through steaming can help prevent cooking losses. Dietary supplementation is another source of obtaining vitamin C and offer vitamin C in the form of ascorbic acid.

The recommended daily intake of vitamin C for adult men is 95mg/day and 75mg/day for adult women. As compiled by the National Institute of Health Office of Dietary Supplements, Table 1 references daily recommended intakes for various age demographics:

Table 1: Recommended Dietary Allowances (RDAs) for Vitamin C [3]

Age Male Female Pregnancy Lactation
0–6 months 40 mg 40 mg    
7–12 months 50 mg 50 mg    
1–3 years 15 mg 15 mg    
4–8 years 25 mg 25 mg    
9–13 years 45 mg 45 mg    
14–18 years 75 mg 65 mg 80 mg 115 mg
19+ years 90 mg 75 mg 85 mg 120 mg
Smokers Individuals who smoke require 35 mg/day more vitamin C than non-smokers.

Metabolism of Vitamin C:

Vitamin C exists as two forms within the body; ascorbic acid (reduced form) and dehydroascorbic acid (oxidized form). Ascorbic acid is the predominant form that exists as most of the oxidized form is converted to ascorbic acid. Absorption of vitamin C occurs in the distal small intestine through the apical membrane of the epithelial cells through an active transport sodium symport system [5]. The body is capable of absorbing 100mg/day of vitamin C. As absorption is an enteral process, there are limits on how much can be absorbed. Anything in excess of 1g/day reduces vitamin C absorption to fifty percent, reducing the bioavailability [6].

Measurement of Vitamin C:

While no definitive methods of measurement have been established for vitamin C, several methods exist to demonstrate vitamin C markers. Plasma and leukocyte vitamin C concentrations remain the most reliable markers [7]. In measuring plasma, one can measure ascorbic acid only, assess ascorbic acid and dehydroascorbic acid separately, or evaluate the total level of vitamin C, which entails taking the sum of ascorbic acid and dehydroascorbic acid, through high-performance liquid chromatography [8]. The reference range for plasma levels of vitamin C falls between 0.4-2mg/dL [30]

Vitamin C Toxicity:

Being a water-soluble molecule, vitamin C is associated with low toxicity in comparison to the fat-soluble vitamins [1]. Most common complaints associated with excessive vitamin C intake include: diarrhea, nausea, abdominal cramping, and various gastrointestinal issues due to unabsorbed vitamin C [3,10]. There is conflicting evidence linking excessive intake with precipitation of oxalate stones in men. However, in the absence of any renal impairment, or pre-existing hyperoxaluria, this is not a concern [9]. In patients with hereditary hemochromatosis, taking vitamin C supplements is not recommended as this can cause iron overload with resultant tissue damage [3,10]. Similarly, although very rare, excessive quantities of vitamin C have been associated with fatal cardiac arrythmias in patients with iron overload. To prevent this, it is advisable to discourage pharmacological vitamin C supplementation [11].

Table 2, borrowed from the National Institute of Health Office of Dietary Supplements, provides the tolerable upper limits of vitamin C intakes of various age populations:

Table 2: Tolerable Upper Intake Levels (ULs) for Vitamin C [3]

Age Male Female Pregnancy Lactation
0–12 months Not possible to establish* Not possible to establish*    
1–3 years 400 mg 400 mg    
4–8 years 650 mg 650 mg    
9–13 years 1,200 mg 1,200 mg    
14–18 years 1,800 mg 1,800 mg 1,800 mg 1,800 mg
19+ years 2,000 mg 2,000 mg 2,000 mg 2,000 mg

Vitamin C Deficiency:

The primary outcome of vitamin C deficiency is scurvy. Scurvy can develop within one month of the body receiving little to no vitamin C [3,12,13]. Symptoms begin as fatigue and malaise with inflammation of the gums. This inflammation can progress to bleeding gums. As the deficiency progresses, collagen synthesis is weakened which contributes to poor wound healing. It is common to see petechiae, ecchymoses, and purpura, along with perifollicular hemorrhaging, bruising and even arthralgias with scurvy [13]. Bone disease can manifest in children with scurvy. Left untreated, scurvy can be fatal [12]. Consuming food sources rich in vitamin C along with supplementation can help correct scurvy when intervened in time. For pediatric cases, 100mg of ascorbic acid provided three times daily through oral, intramuscular, or intravenous methods for 1 week, and then continuous daily vitamin C intake for 1 month should help fight scurvy [14]. Adult populations need between 300-1000mg daily for 1 month to help combat scurvy [12, 13].

Certain groups are at risk for developing vitamin C deficiency. These groups include smokers and those who receive secondhand smoke on a regular basis [3]. This is due to the increased oxidative stress caused by cigarette smoke leading to diminished plasma and leukocyte vitamin C concentrations. Infants that are fed evaporated or boiled milk are at risk due to insufficient vitamin C in milk and the heating process can destroy vitamin C levels [3, 15]. People who live in areas with limited food variety can experience vitamin C deficiency and also those with malabsorptive disorders as not enough vitamin C is being absorbed by the body [3,10,12, 16].

Physiological Involvement of Vitamin C:

Vitamin C supports numerous physiological processes. Vitamin C is primarily a reducing agent, meaning it donates electrons. This function helps support and regulate copper and iron activity in the body including helping aid iron absorption [17]. Tt has antioxidant properties enabling it to reduce molecular oxygen. This antioxidant property help stabilize vitamin E and enables vitamin C to be a co-factor in reducing folate to dihydrofolate or tetrahydrofolate. Further, as a cofactor, vitamin C also helps with neurotransmitter synthesis of catecholamines, especially norepinephrine [18].

In aiding synthesis of physiological processes, vitamin C also supports fatty acid transport in helping to synthesize carnitine [19]. It is presumed that vitamin C may also play a role in prostaglandin metabolism, helping to reduce inflammation.

In discussing scurvy, one of the largest roles vitamin C plays in physiology is in help to support collagen synthesis. Where scurvy leads to collagen breakdown, adequate levels of vitamin C lead to collagen synthesis by supporting the enzymes prolyl hydroxylase and lysyl hydroxylase in forming hydroxyproline and hydroxylysine. These products are formed from the hydroxylation of proline and lysine residues respectively. The formation of these products results in collagen synthesis to maintain proper wound healing, tooth formation, and adequate bone homeostasis [20].

Therapeutic Involvement of Vitamin C:

In having an antioxidant role and having an effect on the immune system, vitamin C has been implicated in numerous pathologies. There is conflicting evidence linking vitamin C consumption with reduced cancer risk. This perceived risk reduction may be in part due to higher consumption of fruits and vegetables (source of vitamin C) however, no substantial evidence and no significant relationship exists linking cancer prevention to dietary or supplementary vitamin C [21-23].

Similarly conflicting evidence exists in examining vitamin C and cardiovascular health. There is limited evidence to show that vitamin C plays a role in reducing atherosclerosis by reducing monocyte adherence to the vascular endothelium [24]. However, many studies show that dietary vitamin C rather than supplemental vitamin C is inversely related to cardiovascular disease [25].

It is a long-held belief that increased vitamin C intake will help to treat and/or prevent the common cold. Again, the evidence is limited. A Cochrane review from 2007 [26] revealed that prophylactic use of vitamin C in the general population did not reduce the incidence of the common cold. However, in extreme physical exercise, such as marathon running or skiing, prophylactic vitamin C did exert a protective role in reducing incidence of the common cold. It is important to note that if taken after onset of the cold, vitamin C does not appear to be beneficial.

With the ongoing pandemic, it is important to examine the role vitamin C plays in treating and managing Covid-19 patients. Research is still ongoing to examine the therapeutic role of vitamin C administration for severe Covid cases, however preliminary limited research findings suggests that administration of vitamin C can lead to significantly reduced mortality. In one meta-analysis vitamin C was shown to decrease ICU stay by 8 percent [29]. It is important to note that vitamin C must be given as an adjunct to other treatment and management options [27]. Vitamin C only plays a supportive role in treating Covid. Figure 1[28] highlights some beneficial effects of vitamin C on Covid-19.

Figure 1: The possible beneficial effects of Vitamin C in the management of Covid-19 [27]


Vitamin C also known as ascorbic is a water-soluble vitamin that plays a supportive role in maintaining homeostasis. Given its pleiotropic nature, the application of vitamin C within the medical setting is widespread and effective when provided as an adjunct to other treatments. It’s use as a mainstay therapeutic warrants further research consideration especially when dealing with novel pathologies such as Covid-19. Toxicity to vitamin C is rare and it can be sourced readily through regular dietary sources and supplementation. It is imperative to maintain adequate levels of vitamin C to preserve normal bodily functions.


  1. Carr, A. C., & Maggini, S. (2017). Vitamin C and Immune Function. Nutrients, 9(11), 1211.
  2. Li, Y., & Schellhorn, H. E. (2007). New developments and novel therapeutic perspectives for vitamin C. The Journal of nutrition, 137(10), 2171–2184.
  3. Office of Dietary Supplements – Vitamin C. (2021). Retrieved 30 August 2021, from Department of Agriculture, Agricultural Research Service. FoodData Central, 2019.
  4. Lykkesfeldt, J., & Tveden-Nyborg, P. (2019). The Pharmacokinetics of Vitamin C. Nutrients, 11(10), 2412.
  5. Glatthaar, B. E., Hornig, D. H., & Moser, U. (1986). The role of ascorbic acid in carcinogenesis. Advances in experimental medicine and biology, 206, 357–377.
  6. Collie, J., Greaves, R., Jones, O., Eastwood, G. & Bellomo, R. (2020). Vitamin C measurement in critical illness: challenges, methodologies and quality improvements: . Clinical Chemistry and Laboratory Medicine (CCLM), 58(4), 460-470.
  7. Jacob R. A. (1990). Assessment of human vitamin C status. The Journal of nutrition, 120 Suppl 11, 1480–1485.
  8. Ferraro, P. M., Curhan, G. C., Gambaro, G., & Taylor, E. N. (2016). Total, Dietary, and Supplemental Vitamin C Intake and Risk of Incident Kidney Stones. American journal of kidney diseases : the official journal of the National Kidney Foundation, 67(3), 400–407.
  9. Jacob, R. A., & Sotoudeh, G. (2002). Vitamin C function and status in chronic disease. Nutrition in clinical care : an official publication of Tufts University, 5(2), 66–74.
  10. McLaran, C. J., Bett, J. H., Nye, J. A., & Halliday, J. W. (1982). Congestive cardiomyopathy and haemochromatosis–rapid progression possibly accelerated by excessive ingestion of ascorbic acid. Australian and New Zealand journal of medicine, 12(2), 187–188.
  11. Weinstein, M., Babyn, P., & Zlotkin, S. (2001). An orange a day keeps the doctor away: scurvy in the year 2000. Pediatrics, 108(3), E55.
  12. Hirschmann, J. V., & Raugi, G. J. (1999). Adult scurvy. Journal of the American Academy of Dermatology, 41(6), 895–910.
  13. American Academy of Pediatrics Committee on Nutrition. Water-soluble vitamins. In: Pediatric Nutrition, 8th ed, Kleinman RE, Greer FR (Eds), American Academy of Pediatrics, 2019. p.655.
  14. Bates C. J. (1997). Bioavailability of vitamin C. European journal of clinical nutrition, 51 Suppl 1, S28–S33.
  15. Hoffman F. A. (1985). Micronutrient requirements of cancer patients. Cancer, 55(1 Suppl), 295–300.<295::aid-cncr2820551315>;2-x
  16. Ross, A. C., Caballero, B., Cousins, R. J., Tucker, K. L., & Ziegler, T. R. (2012). Modern nutrition in health and disease (No. Ed. 11). Lippincott Williams & Wilkins.
  17. Carr, A. C., Shaw, G. M., Fowler, A. A., & Natarajan, R. (2015). Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?. Critical care (London, England), 19, 418.
  18. Rebouche C. J. (1995). Renal handling of carnitine in experimental vitamin C deficiency. Metabolism: clinical and experimental, 44(12), 1639–1643.
  19. Pinnell S. R. (1982). Regulation of collagen synthesis. The Journal of investigative dermatology, 79 Suppl 1, 73s–76s.
  20. Long, Y., Fei, H., Xu, S., Wen, J., Ye, L., & Su, Z. (2020). Association about dietary vitamin C intake on the risk of ovarian cancer: a meta-analysis. Bioscience reports, 40(8), BSR20192385.
  21. Zhang, D., Xu, P., Li, Y., Wei, B., Yang, S., Zheng, Y., Lyu, L., Deng, Y., Zhai, Z., Li, N., Wang, N., Lyu, J., & Dai, Z. (2020). Association of vitamin C intake with breast cancer risk and mortality: a meta-analysis of observational studies. Aging, 12(18), 18415–18435. Advance online publication.
  22. Parent, M. E., Richard, H., Rousseau, M. C., & Trudeau, K. (2018). Vitamin C Intake and Risk of Prostate Cancer: The Montreal PROtEuS Study. Frontiers in physiology, 9, 1218.
  23. Honarbakhsh, S., & Schachter, M. (2009). Vitamins and cardiovascular disease. The British journal of nutrition, 101(8), 1113–1131.
  24. Ye, Z., & Song, H. (2008). Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology, 15(1), 26–34.
  25. Douglas, R. M., Hemilä, H., Chalker, E., & Treacy, B. (2007). Vitamin C for preventing and treating the common cold. The Cochrane database of systematic reviews, (3), CD000980.
  26. Bae, M., & Kim, H. (2020). Mini-Review on the Roles of Vitamin C, Vitamin D, and Selenium in the Immune System against COVID-19. Molecules (Basel, Switzerland), 25(22), 5346.
  27. Abobaker, A., Alzwi, A. & Alraied, A.H.A. Overview of the possible role of vitamin C in management of COVID-19. Pharmacol. Rep 72, 1517–1528 (2020).
  28. Hemilä, H., & Chalker, E. (2020). Vitamin C as a Possible Therapy for COVID-19. Infection & chemotherapy. VITC – Clinical: Ascorbic Acid (Vitamin C), Plasma. (2021). Retrieved 30 August 2021, from

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Vitamin K: Current Knowledge and Areas of Advancement

January 17th, 2022
How to cite this article:

Magsakay CR, Joy BK, Grewal VP. Vitamin K: Current Knowledge and Areas of Advancement. 2022. Journal of Vita Columbia. 2(1).


Vitamin K is recognized for its important role in blood coagulation. Little did we know that it has other vital functions in the human body. Current research findings show its function in bone mineralization, inhibition of vascular calcification, tumor suppression, and inducing insulin sensitization. These benefits offer novel supportive approach in the management of certain diseases including Covid-19.


Vitamin K is a fat-soluble vitamin and its long time well-known function within the body is in the production of coagulation factors (II, VII, IX, X, protein C, and protein S). Moreover, Vitamin K is also involve in the formation of bones (osteocalcin), anticalcification (matrix-Gla protein), cancer prevention and as an insulin sensitizing molecule. Vitamin K is available naturally as Vitamin K1 (phylloquinone) and Vitamin K2 (menaquinone). Vitamin K1 is mostly found among green leafy vegetables (broccoli, brussels sprouts, cabbage, kale, kai-lan, etc.).1 Dark leaf color has more substantial amount of phylloquinones. The other sources of phylloquinone are found in certain plant oils such as soybean, canola, cottonseed, and olive.2 The recommended adequate intake of phylloquinone is 90 μg/day for women and 120 μg/day for men..3 Menaquinones, on the other hand, are found in foods of animal in origin, like bovine liver, and in foods which are fermented with bacteria such as yogurt and other types of cheese. They differ in structure from phylloquinone in their 3-substituted liphophilic side chain. The major menaquinones has 4-10 repeating isoprenoid designated by MK-4 to MK-10.2 The most important menaquinones which has preventive and therapeutic values are menaquinone-4 (MK-4) and menaquinone-7 (MK-7).4 Natto, a traditional Japanese food, which is made from bacterially fermented soya beans, has the richest source of MK-7 with 10 μg/g. Another form of Vitamin K is Menadione (K3). It is not considered a natural form of Vitamin K but a synthetic equivalent that function as a provitamin. Once absorbed in the body, K3 becomes alkylated into a biologically active isoprenylated menaquinones. The difference of K3 among the other vitamins is that it has limitations in its function. K3 is unable to apply all the functions of the natural forms of Vitamin K.14 However, vitamin K3 has been found out to exhibit antitumor activity.

Vitamin K and Coagulation

The classic role of Vitamin K is in the production of proteins needed for coagulation. This is exemplified in vitamin K deficiency states as seen in newborns. In the classic Hemorrhagic Disease of the Newborn (HDN), vitamin K deficiency may cause unexpected bleeding in 0.25% to 1% neonates in the first week of life.5 The administration of a single dose of 0.5 to 1.0 mg of Vitamin K as prophylaxis in newborns has been well-established in the prevention of the classic hemorrhagic disease of newborn. In infants aged 2 to 12 weeks who are exclusively breast-fed and have received no or inadequate vitamin K prophylaxis, a condition known as late hemorrhagic disease of newborn may occur. Infants who have malabsorption defects in the intestine (cholestatic jaundice, cystic fibrosis, etc.) may also manifest with late hemorrhagic disease of the newborn. The administration of parenteral neonatal vitamin K prophylaxis is shown to prevents the development of late HDN. 5

Vitamin K and Bone Health:

Vitamin K is an essential cofactor for the carboxylation of osteocalcin that helps in bone formation.6 Vitamin K and 1,25-dihydroxyvitamin D [1,25 (OH)2D; calcitriol] regulate the activation and production of osteocalcin. The transcription of the osteocalcin gene is supported by 1,25 (OH)2D, while vitamin K assists in the posttranscriptional carboxylation of Gla residues in the osteocalcin propeptide.4 Additionally, it was established that 1,25 (OH)2D complements the activity of γ-glutamyl carboxylase, which implies that the carboxylation of osteocalcin is accelerated by Vitamin D and that MK-4 activates 1,25-dihydroxyvitamin D3-induced mineralization by human osteoblasts. Both vitamin K and vitamin D are involved synergistically on bone health. Thereby, low vitamin K status was identified to be linked with low bone mass, osteoporosis, and fracture risk.7 In the Nurses’ health study, which is a 10-year prospective study of women aged 38-63, it was found out that undercarboxylated osteocalcin can be lowered with high intakes of Vitamin K-rich foods and that there is a positive association with risk of hip fractures with undercarboxylated osteocalcin. It was observed that an increased risk of hip fracture was seen in women with lowest vitamin K intake.8 In the Framingham offspring study conducted to determine the effect of vitamin K intake in bone mineral density, it was determined that low dietary phylloquinone intake was associated with low bone mineral density. The results of this study promoted support to the assumption that vitamin K is a reversible factor that help reduce bone loss due to aging.9 Patients who have chronic renal failure also undergo bone mineral disturbances. In the study conducted by Kohlmeier et al, they investigated a total of 68 patients (33-91 years) on hemodialysis and analyzed the association between biochemical indicators of vitamin K nutrition and bone metabolism, and related fracture risk. After a four-year follow-up period, there were 41 patients who did not develop any fracture and it was notable that these patients have close to three times higher concentrations of phylloquinone than the nine patients with fracture.10

Vitamin K and Vascular Health:

While vitamin K plays a significant role in the carboxylation of osteocalcin which helps in the formation of bones, the vitamin K-dependent Matrix Gla Protein (cMGP) prevents blood vessels from developing calcification from calcium overload.4 The matrix Gla-protein was discovered in human atherosclerotic plaque where its role help prevent the precipitation of calcium as what it does in bone. It was assumed that a diet with insufficient intake of vitamin K may also lead to under carboxylation of vascular matrix Gla protein which may result to calcification of atherosclerotic lesions, and, therefore, a heightened risk of developing coronary heart disease. In the Rotterdam Study conducted to determine the association of dietary intake of Menaquinone with Coronary Heart Disease, they have observed that dietary menaquinone intake has a protective effect from coronary artery disease in older men and women as determined by the inverse association with all-cause mortality. The patients in the highest quartile for K2 intake had a median intake of 40.9 μg/day. Moreover, cancer risk does not rise with high menaquinone dietary intake.11 On the other hand, phylloquinone intake had no association with coronary heart disease, mortality, or in the calcification of aorta. Gast et al also did a study similar to the Rotterdam study, where they also found an inverse relationship with menaquinone dietary intake and coronary heart disease. The protective effect of Vitamin K2 is manifested in subtypes MK-7 through MK-9.12 However, more studies should be done in the future to determine the adequate dose of Vitamin K in the prevention of coronary heart disease.  

In patients with chronic kidney disease, warfarin is frequently prescribed to inhibit venous thromboembolism, atrial fibrillation and for access-related issues. Warfarin then impedes the vitamin K epoxide reductase enzyme, interrupting the reduction of the epoxide and inhibits the cycling back to the hydroquinone intermediate, which then interrupts the blood coagulation cascade.13 The resultant low tissue levels of vitamin K leads to formation of inactive MGP which is not able to counteract vascular calcification. Conversely with a high vitamin K dietary intake, tissue levels of vitamin K are increased then rising the amount of active MGP, and, therefore, heightens the vascular calcification inhibitory action. McCabe et al demonstrated in their study a rodent model of chronic kidney disease (CKD), and the role of vitamin K as a possible treatment option to lessen the development of vascular calcification in CKD. Their study showed that those given with therapeutic doses of warfarin had accelerated vascular calcification in all the vessels studied (renal artery, carotid artery, abdominal aorta, and thoracic aorta) and displayed changes within the circulation (elevated pulse pressure and pulse wave velocity). Their results suggested that in the setting of chronic kidney disease, vitamin K levels are critical in preventing vascular calcification.13

Vitamin K and Cancer Prevention:

There are numerous vitamin K dependent proteins that are identified as specific ligands for tyrosine kinase receptors. These receptors play a significant role in cell signaling processes like cellular survival, transformation, and replication. Vitamin K3, Menadione, possess antitumor activity and has been studied since 1947. Oztopcu et al reported that vitamin K has possible antiproliferative effect on both C6 and the low passage human glioma cells. When these cell types are compared, the antiproliferative effect of vitamin K3 was stronger on the human glioma cells than on C6 cells.15 Jamison et al showed that the combination of vitamins C and K3 resulted in the inhibition of growth in prostate cancer cells, potentiation of cancer chemotherapy and radiotherapy and reduced the incidence of cancer metastases. This vitamin combination may be considered as an alternative, non-toxic adjuvant cancer treatment, which may be considered in clinical cancer therapy.16 Although most anticancer research studies in vitamin K focused on vitamin K3, there were also studies that presented the effects of K1 and K2 on anticancer cells. In the study of Prasad Et al, they observed that vitamin K3 inhibited the growth of neuroblastoma, melanoma and glioma cells cultured in serum-supplemented medium in rats. In comparison to glioma or melanoma cells, neuroblastoma cells were more sensitive to vitamin K3. Vitamin K3 was more efficacious than vitamin K1.17 Haruna et al showed that sorafenib + vitamin K2 combination treatment had a much higher response (27.3%) than sorafenib only (4.5%) in the treatment of Hepatocellular carcinoma. The median time of progression free survival was increased in the vitamin K-dosed group compared with the sorafenib alone group. In the vitamin K-dosed group, 75% of patients with tumor size reduction achieved a complete response or partial response, while only 13% of patients with tumor size reduction showed a partial response in the sorafenib only group. The study demonstrated that Vitamin K alone may not weaken tumor growth and that the combination of vitamin K with sorafenib could enhance antitumor effects.18 More studies are needed to determine the role of vitamin K in tumor reduction either acting alone or in combination with other chemotherapeutic agents.

Vitamin K and Insulin Sensitivity:

The protective effect of Vitamin K2 is also observed in patients with Diabetes Mellitus. However, there is limited evidence that vitamin K is inversely associated with insulin resistance. Under-carboxylated osteocalcin was observed to function as an endocrine hormone which affects the metabolism of glucose in mice.19 It has been proposed that vitamin K, which converts the uncarboxylated osteocalcin to a carboxylated form, helps regulate glucose metabolism through modulating osteocalcin and/or proinflammatory pathway. In the study of Choi et al, they have demonstrated that vitamin K2 supplementation for 4 weeks increased the insulin sensitivity in healthy young males which is related to increased carboxylated osteocalcin rather than inflammatory modulation.20  Yoshida et al showed in their study that a daily supplementation of 500ug of phylloquinone for 36 months had a protective effect on progression of insulin resistance in older men.21 In another study conducted by Yoshida et al, they confirmed that a higher phylloquinone intake was associated with greater sensitivity of insulin and glycemic status as measured by 2-hour post-oral-glucose-tolerance test insulin, glucose, and insulin sensitivity index in a community-based sample of men and women.22

Vitamin K and Covid-19:

Vitamin K is an important factor in the activation of pro and anti-clotting factors in the liver and Protein S outside of the liver (local antithrombotic). Beyond coagulation, Vitamin K also plays an important role in other tissue functions like soft tissue calcification and elastic fibre degradation, which is mediated by Matric Gla Protein, a vitamin K dependent inhibitor. It is observed that in Covid-19 patients these functions are altered leading to lung fibrosis. The study also demonstrated significantly low levels of vitamin K in sick Covid-19 patients23. Another study conducted in hospitalised Covid-19 patients showed that low levels of vitamin K has been associated with higher mortality in sick patients24. More trials have to be conducted to learn about the  potential role of vitamin K in the treatment and progression of Covid-19.


The role of vitamin K encompasses its well-known function in coagulation. It is noteworthy that vitamin K is a powerful and essential vitamin that prevents fractures, vascular calcification, cancer, and promotes insulin sensitivity in patients with Diabetes Mellitus. The findings stated in numerous studies investigating the action of vitamin K in certain diseases may help clear novel properties of vitamin K and its protective effect in human health. Future studies should also explore the appropriate dosing of vitamin K supplementation required in the prevention of these diseases.


  1. Mladenka P, Macakova K, Krcmova L, Javorska L, Mrstna K, Carazo A, Protti M, Remiao F, Novakova (2021). Vitamin K – sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity. Nutrition Reviews Journal 00(0):1-22.
  2. Booth, S. Vitamin K: food composition and dietary intakes (2012). Food and Nutrition Research 56(5505). doi:3402/fnr. v56i0.5505
  3. Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. Available from: Doi: 10.17226/10026
  4. Gröber U, Reichrath J, Holick MF, Kisters K. Vitamin K: an old vitamin in a new perspective. Dermatoendocrinol. 2015 Jan 21;6(1):e968490. doi: 10.4161/19381972.2014.968490. PMID: 26413183; PMCID: PMC4580041.
  5. American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn. Pediatrics. 2003 Jul;112(1 Pt 1):191-2. PMID: 12837888.
  6. Hauschka PV, Lian JB, Gallop PM (1975) Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proceedings of the National Academy of Sciences. 72 (10) 3925-3929; DOI: 10.1073/pnas.72.10.3925
  7. Vermeer C. Vitamin K: the effect on health beyond coagulation – an overview. Food Nutr Res. 2012;56. Doi: 10.3402/fnr. v56i0.5329. Epub 2012 Apr 2. PMID: 22489224; PMCID: PMC3321262.
  8. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999 Jan;69(1):74-9. Doi: 10.1093/ajcn/69.1.74. PMID: 9925126.
  9. Sarah L Booth, Kerry E Broe, David R Gagnon, Katherine L Tucker, Marian T Hannan, Robert R McLean, Bess Dawson-Hughes, Peter WF Wilson, L Adrienne Cupples, Douglas P Kiel, Vitamin K intake and bone mineral density in women and men, The American Journal of Clinical Nutrition, Volume 77, Issue 2, February 2003, Pages 512–516,
  10. Kohlmeier M, Saupe J, Shearer MJ, Schaefer K, Asmus G. Bone health of adult hemodialysis patients is related to vitamin K status. Kidney Int. 1997 Apr;51(4):1218-21. Doi: 10.1038/ki.1997.166. PMID: 9083289.
  11. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5. Doi: 10.1093/jn/134.11.3100. PMID: 15514282.
  12. Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504-10. Doi: 10.1016/j.numecd.2008.10.004. Epub 2009 Jan 28. PMID: 19179058.
  13. McCabe KM, Booth SL, Fu X, Shobeiri N, Pang JJ, Adams MA, Holden RM. Dietary vitamin K and therapeutic warfarin alter the susceptibility to vascular calcification in experimental chronic kidney disease. Kidney Int. 2013 May;83(5):835-44. Doi: 10.1038/ki.2012.477. Epub 2013 Jan 23. PMID: 23344475.
  14. Lamson DW, Plaza SM. The anticancer effects of vitamin K. Altern Med Rev. 2003 Aug;8(3):303-18. PMID: 12946240.
  15. Oztopçu P, Kabadere S, Mercangoz A, Uyar R. Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human glioblastoma multiforme cells in vitro. Acta Neurol Belg. 2004 Sep;104(3):106-10. PMID: 15508263.
  16. Jamison, James & Gilloteaux, Jacques & HS, Taper & P, Buc & Perlaky, Laszlo & Thiry, Marc & Neal, Deborah & Blank, James & RJ, Clements & Summers, Jack. (2005). The In Vitro and In Vivo Antitumor Activity of Vitamin C: K3 Combinations Against Prostate Cancer. Retrieved from:
  17. Kedar N. Prasad, Judith Edwards-Prasad, Arthur Sakamoto. Vitamin K3 (menadione) inhibits the growth of mammalian tumor cells in culture, Life Sciences, Volume 29, Issue 13, 1981, Pages 1387-1392, ISSN 0024-3205,
  18. Haruna Y, Yakushijin T, Kawamoto S. Efficacy and safety of sorafenib plus vitamin K treatment for hepatocellular carcinoma: A phase II, randomized study. Cancer Med. 2021 Feb;10(3):914-922. Doi: 10.1002/cam4.3674. Epub 2021 Jan 22. PMID: 33481328; PMCID: PMC7897941.
  19. Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5266-70. Doi: 10.1073/pnas.0711119105. Epub 2008 Mar 24. PMID: 18362359; PMCID: PMC2278202.
  20. Choi HJ, Yu J, Choi H, An JH, Kim SW, Park KS, Jang HC, Kim SY, Shin CS. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care. 2011 Sep;34(9): e147. Doi: 10.2337/dc11-0551. PMID: 21868771; PMCID: PMC3161300.
  21. Yoshida M, Jacques PF, Meigs JB, Saltzman E, Shea MK, Gundberg C, Dawson-Hughes B, Dallal G, Booth SL. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care. 2008 Nov;31(11):2092-6. Doi: 10.2337/dc08-1204. Epub 2008 Aug 12. PMID: 18697901; PMCID: PMC2571052.
  22. Makiko Yoshida, Sarah L Booth, James B Meigs, Edward Saltzman, Paul F Jacques, Phylloquinone intake, insulin sensitivity, and glycemic status in men and women, The American Journal of Clinical Nutrition, Volume 88, Issue 1, July 2008, Pages 210–215,
  23. Janssen R, Visser MPJ, Dofferhoff ASM, Vermeer C, Janssens W, Walk J. Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019. Br J Nutr. 2021 Jul 28;126(2):191-198. doi: 10.1017/S0007114520003979. Epub 2020 Oct 7. PMID: 33023681; PMCID: PMC7578635.
  24. Linneberg A, Kampmann FB, Israelsen SB, Andersen LR, Jørgensen HL, Sandholt H, Jørgensen NR, Thysen SM, Benfield T. The Association of Low Vitamin K Status with Mortality in a Cohort of 138 Hospitalized Patients with COVID-19. Nutrients. 2021 Jun 9;13(6):1985. doi: 10.3390/nu13061985. PMID: 34207745; PMCID: PMC8229962.

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Vitamin D: Overview, metabolism, deficiency and supplementation

January 17th, 2022
How to cite this article:

Saiki O and Grewal VP. Vitamin D: Overview, metabolism, deficiency and supplementation. 2022. Journal of Vita Columbia. 2(1).


Vitamin D is a hormone primarily responsible for bone and calcium metabolism. It also has other extra-skeletal effects; vitamin D receptors are present in almost all parts of the body.1 Vitamin D is primarily obtained from sunlight through the action of Ultraviolet B(UVB) radiation; it is also gotten from plant sources. Vitamin D in whatever form is converted to its active form 1,25 cholecalciferol in the kidney. Vitamin D deficiency has serious implications on the body; it affects the musculoskeletal system, immunity and cardiovascular system. Its deficiency has also been linked to the development of some cancers.1 Due to the role played by Vitamin D in these Organs and systems, it is essential that its deficiency is treated, and when required, individuals should have vitamin D supplementation.


Vitamin D is a steroid hormone responsible for bone and calcium homeostasis. However, some other studies have identified its role in other extra-skeletal activities like cardiovascular disease and autoimmune diseases.1,2 There have even been more recent concerns regarding the role of vitamin D deficiency in causing chronic lung fibrosis; this has significant relevance in patients with COVID 19 disease.3,4

Metabolism of Vitamin D:

Vitamin D is a fat-soluble hormone and exists in two forms. The first form is vitamin D3 which animals produce from the skin, and Vitamin D2 produced by plants.5 Vitamin D is produced in the skin from 7-dehydrocholesterol(7DHC), an intermediate of cholesterol through the action of Ultraviolet B (UVB) radiation. The synthesis of Vitamin D depends on the concentration of 7-dehydrocholesterol reductase; this enzyme catalyzes the reversible reduction of 7DHC into cholesterol. Vitamin D then undergoes two processes of hydroxylation to be converted to its active form, first in the liver (25 hydroxy Vitamin D) and subsequently in the kidney and other organs by 1-α hydroxylase to 1,25- Dihydroxy Vitamin D, Calcitriol. The action of Vitamin D is by its active form, calcitriol, which acts on vitamin D receptors on cells.5

Local production of the active form of Vitamin D have been described in some extra-renal organs such as; Epithelial cells, placenta, bone, brain, liver, endothelial cells and endocrine glands (parathyroid, thyroid, pancreatic islets, adrenal medulla and gonads). Regulation of active vitamin D productions thus occurs within the kidneys and extrarenal.2,5

Vitamin D is classically known for its role in bone and calcium metabolism, including renal calcium absorption, regulation of intestinal calcium absorption and release of calcium and phosphate from the bone. However, in recent times, more researches have been done showing other roles of Vitamin D in multiple organs/system which include; Cardiovascular system, immune system, adipose tissues, glucose/lipids metabolism, muscles and in cancer prevention.2,5

Cardiovascular system: Vitamin D has been shown to have a direct effect on cardiomyocytes and vasculature. Low vitamin D level has been associated with an increased risk of cardiovascular diseases such as hypertension, stroke, heart failure, coronary artery disease and ischaemic artery disease. A low level of Vitamin D has also been found to affect the prognosis of patients with cardiovascular diseases adversely.6,7

Immune System: Vitamin D plays a major role in the immune system ( innate and acquired). It stimulates production of IL-10, which has anti-inflammatory properties. It also decreases the release of pro-inflammatory cytokines such as IL-6 and TNFα. Vitamin D deficiency has been associated with increased risk of infection and autoimmune diseases.8,9 A large meta-analysis has shown that vitamin D prophylaxis prevented the development of acute respiratory infections in adults. These findings establish a pedestal for further research on the role of Vitamin D in the prevention of SARS-COV2 infections.10 Some studies have reported low vitamin D levels in patients being treated for COVID-19 infection, and those with these low levels had worse prognosis. The role of vitamin D in preventing acute respiratory infection may be due to its immune function and also the fact that respiratory infection occurs more during the winter when there is no sunshine, thus affecting vitamin D production.3,4

Glucose/Lipid metabolism: low level of vitamin D has been associated with metabolic syndrome. Vitamin D receptor has been found to be present in all cells responsible for both type 1 and 2 diabetes mellitus. A low level of Vitamin D level has been reported as a risk factor for development of diabetes mellitus in animal models, though this is yet to be substantiated in human studies.11

Muscle: It has also been reported that vitamin helps to improve muscle strength and function in both adults and children.12,13

Cancer: Vitamin D receptors have been expressed in some cancer cell lines, and it has been studied for its role in cancer. Vitamin D has been proven to have an anti-proliferative effect on melanoma, myeloma cells, and other cancer cell lines. However, its role on cancer is still controversial as more studies is being carried out.14,15

Vitamin D Deficiency:

Vitamin D deficiency is a global problem affecting over 1 billion children and adults worldwide.2 Its deficiency is associated with adverse acute and chronic medical conditions, which include: Dental caries in childhood, preeclampsia, cardiovascular diseases, autoimmune disorders, infectious diseases, type 2 Diabetes mellitus, some malignancies and neurological diseases.1,2 Vitamin D deficiency may also cause muscle weakness, bone loss, rickets in children, and increased fracture risk.

There are some risk factors for Vitamin D deficiency, the diagram below illustrates the various risk factors for vitamin D deficiency. Vitamin level is measured using 25(OH) D levels, a level of less than 20ng/ml is considered low.

Treatment of Vitamin D Deficiency:

Vitamin D is primarily gotten from sunlight; however, some can be gotten from plant sources. Both D2(Ergocalciferol) and D3(Cholecalciferol) are available as dietary supplements.1,2,16 Vitamin D2 is found in some mushrooms while vitamin D3 is found in oily fish, fish liver oil and egg yolk.  Vitamin D supplementation is necessary to improve musculoskeletal health and also to decrease mortality from cardiovascular diseases and cancers.16

The national institute of health recommends a daily intake of 400-800IU/day to maintain optimum vitamin D17 level though some other studies recommend as much as 1000-4000iu/day to maintain optimum level.16 However, the amount of vitamin D supplement needed will also depend on other factors such as age, ethnicity, clothing, sun exposure, season and latitude.

Several clinical studies on Vitamin D in pregnancy have reported high prevalence of Vitamin D deficiency in pregnancy with associated adverse effects on the mother and baby.18,19 On the other hand, a couple of randomized controlled trials have showed inconsistent findings.20 Notwithstanding, currently a daily dose of 400-800iu/day of vitamin D is recommended for pregnant women, although some other studies recommend as high as 800-1200iu/day.18

Vitamin D supplementation is also required in the paediatric population in doses ranging from 1000-4000iu/day. Vitamin D supplementation is particularly needed in children with the following conditions; Obesity, cystic fibrosis, insulin resistance, type 1 DM and celiac disease.21

There are still contrasting findings from studies on the role of routine Vitamin supplementation in the prevention of acute respiratory infection. The beneficial effect of vitamin D supplementation in this regard is yet to be proven.22,23

Vitamin D supplementation has also been recommended in some studies for postmenopausal women, reducing falls and improving muscle function.16

It is important that barring all circumstances, Vitamin D level should be maintained to at least 20ng/ml which is the minimum required level, although some researchers report that a level of 30ng/ml and above is the adequate optimal level.1,2

Vitamin D Toxicity:

Vitamin D toxicity is a very rare phenomenon. Excessive exposure to sunlight is not responsible for toxicity. 1,2 Toxicity is caused by either intentional or non-intentional intake of vitamin D supplements for long periods, this leads to excessive absorption of calcium. Its very important for people to know the various doses and accurate unit of measurement of vitamin D supplements. This could present as nausea, vomiting. dehydration, kidney stones, muscle weakness and confusion. Extreme cases of toxicity can lead to renal failure, arrhythmias and death.


Vitamin D is a very important hormone for maintaining musculoskeletal health and other vital functions in the body. The deficiency of Vitamin D is prevalent worldwide and can cause serious effects on the musculoskeletal system, cardiovascular system, immunity and other body functions. It is essential that vitamin supplements be taken to maintain normal levels in the body to help preserve its functions.


  1. Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clinic Proceedings. 2010 Aug;85(8):752-7; quiz 757-8. DOI: 10.4065/mcp.2010.0138. PMID: 20675513; PMCID: PMC2912737.
  2. Holick, M.F. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 18, 153–165 (2017).
  3. Carpagnano, GE., Di Lecce V, Quaranta, VN. et al.Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest 2021;(44): 765–771.
  4. Radujkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M, Merle U. Vitamin D Deficiency and Outcome of COVID-19 Patients. Nutrients [Internet] 2020;(12):2757. Available from:
  5. Saponaro F, Saba A, Zucchi R. An Update on Vitamin D Metabolism. International Journal of Molecular Sciences [Internet] 2020;(21):6573. Available from:
  6. Wang L, Song Y, Manson JE, Pilz S, März W, Michaëlsson, K, Lundqvist A, Jassal SK, Barrett-Connor E, Zhang C et al. Circulating Levels of 25Hydroxy-Vitamin D and Risk of Cardiovascular Disease: A Meta-Analysis of Prospective Studies. Circ. Cardiovasc. Qual. Outcomes 2012; (5): 819–829.[CrossRef]
  7. Judd SE, Tangpricha, V. Vitamin D deficiency and risk for cardiovascular disease. Am. J. Med. Sci. 2009;(338): 40–44. [CrossRef]
  8. Martens P J, Gysemans C, Verstuyf A, Mathieu C. Vitamin D’s Effect on Immune Function. Nutrients 2020;(12): 1248. [CrossRef] [PubMed]
  9. Colotta F, Jansson B, Bonelli F. Modulation of inflammatory and immune responses by vitamin D.J. Autoimmun. 2017;( 85): 78–97. [CrossRef] [PubMed]
  10. Martineau AR, Jolli_e DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde A.A, et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ 2017; 356: i6583.[CrossRef]
  11. Mathieu C. Vitamin D and diabetes: Where do we stand? Diabetes Res. Clin. Pract. 2015; (108): 201–209.[CrossRef] [PubMed
  12. Bischo_-Ferrari HA,Dawson-Hughes B, Baron JA, Burckhardt P, Li R, Spiegelman D, Specker B, Orav JE, Wong JB, Staehelin HB,et al. Calcium intake and hip fracture risk in men and women:A meta-analysis of prospective cohort studies and randomized controlled trials. Am. J. Clin. Nutr. 2007;(86):1780–1790. [CrossRef]
  13. Bischo_-Ferrari HA. Relevance of vitamin D in muscle health. Rev. Endocr. Metab. Disord. 2012;(13): 71–77.[CrossRef]
  14. Colston K, Colston MJ, Feldman D. 1,25-dihydroxyvitamin D3 and malignant melanoma: The presence of receptors and inhibition of cell growth in culture. Endocrinology 1981;(108): 1083–1086. [CrossRef]
  15. Duffy MJ, Murray A, Synnott NC, O’Donovan N, Crown J. Vitamin D analogues: Potential use in cancer treatment. Crit. Rev. Oncol. Hematol. 2017;(112): 190–197. [CrossRef]
  16. ZhangY, Fang F, Tang J, Jia L, Feng Y, Xu P et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis BMJ 2019; (366) :l4673 doi:10.1136/BMJ.l4673
  17. Office of dietary supplements-Vitamin D (2021, July 28). National Institute of health.
  18. Pilz S, Zittermann A, Obeid R, Hahn A, Pludowski P, Trummer C, et al. The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data. International Journal of Environmental Research and Public Health [Internet] 2018;15:2241. Available from:
  19. Hollis BW, Wagner CL. New insights into the vitamin D requirements during pregnancy. Bone Res. 2017;(5): 17030. [CrossRef] [PubMed]
  20. Cooper C, Harvey NC, Bishop NJ, et al. Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomized placebo-controlled trial. Lancet Diabetes Endocrinol2016; (4):393–402.
  21. Cediel G, Pacheco-Acosta J, CastiUo-Durdn C. Vitamin D deficiency in pediatric clinical practice. Archivos Argentinos de Pediatria. 2018 Feb;116(1): e75-e81. DOI: 10.5546/aap.2018.eng.e75. PMID: 29333826.
  22. Martineau AR, Hanifa Y, Witt KD, et al. Double-blind randomized controlled trial of vitamin d3 supplementation for the prevention of acute respiratory infection in older adults and their carers (ViDiFlu). Thorax 2015; (70):953–960.
  23. Denlinger LC, King TS, Cardet JC, et al. Vitamin d supplementation and the risk of colds in patients with asthma. Am J Respir Crit Care Med 2016;(193):634–641.

Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Vitamin A: A Crucial Micronutrient for Immunity, Vision, Reproduction

January 5th, 2022
Blessy K Joy, MBBS
Kevin Joy, BSc, DCh
Wafaa Chorfi, MD
How to cite this article:

Joy BK, Joy K, Chorfi W. Vitamin A: A Crucial Micronutrient for Immunity, Vision, Reproduction. 2022. Journal of Vita Columbia. 2(1).


Retinol, commonly known as vitamin A, is a crucial micronutrient needed for multiple functions in the body including immune functions, vision, and reproduction. Vitamin A comes from both animal and plant sources as well as from fortified cereals. It is absorbed with fat micelles and stored in liver as retinol, and has several therapeutic uses including Covid-19 treatment. This article also covers the deficiency and toxicity of vitamin A and how to treat them. It also showcases some of the controversies of vitamin A and its relationship with certain cancers and cardiovascular diseases, as well as the future scope in research surrounding vitamin A.


Vitamin A is an important micronutrient with antioxidant properties which circulates as Retinol in our body. These are fat soluble retinoids including retinol, retinal and the esterified form [1]. The major sources are vegetarian and animal sources and can be synthesized in the labs as synthetic retinoids for medical uses. It is absorbed from the duodenum and proximal jejunum along with fat molecules and transported with retinol-binding protein (RBP) to liver for storage as retinol [38]. The active form of vitamin A is retinal and retinoic acid, the latter is bound to albumin for transport. Like any other nutrient vitamin A can also cause deficiency and toxicity, both of which must be managed accordingly. It is also used in the treatment of many diseases including measles, HIV, infertility, blindness, and even COVID-19.

Functions of Vitamin A:

  • Immune functions
    Vitamin A is involved in production of leukocytes including natural killer cells, macrophages, and the mucosal barriers. Deficiency of vitamin A can lead to increased susceptibility to infections.

  • Vision
    Vitamin A is a crucial factor in forming rhodopsin which is a protein that absorbs light in the retinal receptors [2], and to some extent in color vision. Deficiency of rhodopsin can cause night blindness and later complete blindness.
  • Reproduction
    In males it is involved in spermatogenesis and oogenesis in females. It plays an important role in placental development, fetal and embryonic growth [38]. Deficiency of vitamin A can lead to infertility and is critical for adequate fetal growth.

Metabolism of Vitamin A:

Vitamin A is a fat-soluble vitamin. Hence, different forms of vitamin A present in food are solubilized into micelles in the duodenal lumen and proximal jejunum from which they are absorbed. Inside the body, both forms of vitamin A are converted into retinol, which is the measurable form. However, the active form of vitamin A is retinal and retinoic acid.

Vitamin A is primarily stored in the liver as retinyl esters. A downside to this is plasma retinol levels will decrease only once the liver stores are depleted. So, dietary deficiency cannot be measured in the early stages. However, liver stores of vitamin A can be measured indirectly through the dose response test. In this test plasma retinol levels are measured before and after the administration of a small amount of vitamin A. An increase of 20% or above in serum retinol levels shows vitamin A deficiency [3]. For regular clinical practice, serum retinol levels are enough.

Sources of Vitamin A:

2 types of vitamin A that are found in human diet which includes [3]:

  1. Preformed vitamin A
  2. Provitamin A

Preformed vitamin A consists of retinyl ester and retinol. Major sources include animal products like fish, and meat specifically liver. Among provitamin A carotenoids the most important one is beta-carotene and is mainly obtained from plant sources. Provitamin A is converted into its active form, i.e., retinal, and retinoic acid within our body [3]. Other sources of vitamin A include fortified cereals.

Table 1. Vitamin A Content In Selected Foods [39, 40]
Amaranth – raw leaf


Apple 7
Beet 487 Apricot (dried) 210-1,090
Broccoli, boiled 60


Cabbage Green 10 Banana 10-21
Red 3


Carrot 1,200


Dandelion 1,200-1367 Mango Ripe 118-400
Kale 150-1,263 Unripe 10
Lettuce 325 Dried 733-887
Okra 121 Raspberry 10
Potato Trace – 3 Watermelon 8-58
Pumpkin 166 OILS
Spinach, boiled 573 Coconut oil 0
Rice – parboiled 0 Olive oil 4
Sweet potato (boiled) 291 Red palm oil 2,035-24,647
Taro (leaf, boiled) 783 FISH
MILK AND EGG Oyster 90-96
Buffalo milk 64 Salmon, cooked 70
Cow milk 29-38 Tuna 80-830
Goat milk 19-71 MEAT
Yoghurt, plain 23 Beef 25
Chicken egg 260


Duck egg 740 Goat


*All values are for raw food unless specified.

Total vitamin A activity (RAE) per 100g of edible portion

Clinical Uses of Vitamin A:

Vitamin A has several therapeutic implications.

  1. Measles – Administering vitamin A to children with measles has shown to reduce the complications and mortality associated with the disease [41].
  2. Dermatology – Synthetic retinoids like isotretinoin is used in treating conditions like psoriasis, hyperkeratosis, skin cancer etc. It is also used in the treatment of acne both topically and systemically. Due to teratogenicity of vitamin A, precaution is taken not to get pregnant while on retinoic acid [42].
  3. Atherosclerosis – Attributable to the antioxidative properties of retinol, it may be useful in preventing cardiovascular disease. But this is controversial as certain studies have pointed that it may increase the likelihood of lung cancer and cardiovascular diseases [15].
  4. Acute promyelocyte leukemia (a subgroup of Acute Myelocytic Leukemia) – All Trans Retinoic Acid or tretinoin, a metabolite of vitamin A, is used in treatment of acute promyelocytic leukemia in conjunction with chemotherapy [43].
  5. Very low birth weight infants – Studies have shown a decline in the incidence of bronchopulmonary dysplasia in very low birthweight infants after supplementing with vitamin A [16].
  6. Age Related Macular Degeneration – The probable etiology for ARMD is oxidative stress, for which reason Vitamin A is beneficial in the treatment and prevention of ARMD by giving supplements containing carotenoids [17].

Recommended Daily Allowance (RDA) of Vitamin A:

The recommended daily allowance for vitamin A is measured as retinol activity equivalents (RAE).

1 RAE = 1 mcg retinol or 3.3 IU [5]

Table 2 – Showing Vitamin A Requirements for Different Age Groups [3]

Age group

RDA/AI* (microgram)

UL (maximum daily intake)

0-6 months



7-12 months




1-3 years



4-8 years



9-13 years



14-18 years



>19 years




9-13 years



14-18 years



>19 years



<18 years



>18 years



<18 years



>18 years



Note: RDA – recommended dietary allowance

AI – adequate intake, it means this level is expected to ensure nutritional adequacy and it is given where the evidence is not satisfactory to get an RDA

UL – upper limit, which is the maximum daily intake that will not cause adverse effect

Vitamin A Deficiency:

A plasma retinol level less than 0.70 micromol/L is considered deficiency [4]. Another indicator for vitamin A deficiency is serum retinol-binding protein (RBP).

Vitamin A deficiency is relatively rare in North America. However, the prevalence is approximately between 30% – 50% in the developing world, (figure1), especially in the preschool children [13]. It is one of the leading cause for blindness in underdeveloped countries. Hence, Vitamin A supplementation is included in the vaccination schedule of children in both developing and underdeveloped countries. Studies have shown that this effort was successful in preventing vitamin A related blindness and deaths.

Vitamin A deficiency causes the disease called Xerophthalmia. The early signs include night blindness or not being able to see in the dark. Other signs are Bitot’s spots in the eye, conjunctival xerosis, corneal xerosis & ulceration, and corneal scarring leading to xeropthalmia. Other health issues include decreased bone health, hyperkeratosis, follicular hyperkeratosis, or phrynoderma, and children are prone to measles and diarrhea [14].

Causes of vitamin A deficiency include dietary deficiency which is the case in developing and underdeveloped countries. Chronic diarrhea in children is also a cause for deficiency of vitamin A in developing countries. However, in developed countries, the cause for deficiency is much different and certain populations are at high risk of deficiency, the major reason for which is malabsorption.

The risk groups for deficiency include;

  1. Pancreatic insufficiency
    Cystic fibrosis patients develop vitamin A deficiency due to associated pancreatic insufficiency where fat absorption is affected. Several studies have shown that 15-40% of patients with cystic fibrosis develop vitamin A deficiency [9]. Cystic fibrosis patients are treated with fat-soluble vitamins at doses higher than their required daily intake. Chronic pancreatitis patients generally do not develop vitamin A deficiency as some of the pancreatic function is still preserved. Short bowel syndrome also causes vitamin A deficiency due to fat malabsorption.
  2. Chronic liver disease
    As the liver is the storehouse of Vitamin A, chronic liver disease can cause deficiency of fat-soluble vitamins like vitamin A. The metabolism of retinol and ethanol occurs through cytochrome P450 leading to increased metabolism of retinol. This combined with decreased dietary intake results in Vitamin A deficiency. However, the process is much more complicated as it can also cause hepatotoxicity when combined with ethanol [10].
  3. Bariatric surgery
    After bariatric surgery the deficiency of vitamin A increases. By about 6 weeks of bariatric surgery 35% showed vitamin A deficiency if not supplemented [11, 12].
  4. Crohn’s disease (CD)
    Due to extensive small bowel involvement, CD patients are at increased risk of fat-soluble vitamin deficiency.
  5. Celiac disease
    Newly diagnosed celiac disease patients might have deficiencies and may require supplementations. But once they are stable with a gluten-free diet, their requirements come back to a normal healthy individual.

Other population that might be at risk for developing vitamin A deficiency, due to inadequate intakes of vitamin A;

  1. Premature infants
    In premature babies the liver stores for vitamin A are not sufficient as the serum levels of retinol remains low for the 1
    st year which makes them susceptible for deficiency related diseases [6].
  2. Infants and young children in developing countries
    In developed or developing countries, breast milk can provide them with adequate vitamin A which will not occur if mothers are deficient of vitamin A [7]. Moreover, the incidence of vitamin A deficiency spikes once the exclusive breastfeeding stops.
  3. Pregnant and lactating women in developing countries
    As the nutritional demands during pregnancy and lactation increases, the need for vitamin A also increases. In developing countries, WHO estimates that 9.8 million pregnant women around the world have xerophthalmia due to Vitamin A deficiency [14].

Treatment of Vitamin A Deficiency

Replacement of vitamin A is the treatment for deficiency. WHO recommends periodic supplementation of vitamin A in endemic population in the suggested doses [37]:

  1. 6 months – 1 year – 10,000 IU PO single dose
  2. 1 year – 5 year – 200,000 IU PO repeated over 4-6 months.
  3. Pregnant women in endemic areas should also receive supplementation – doses <10,000 IU daily
  4. Children in endemic areas are at high risk of deficiency related diseases and should receive supplements if they haven’t received the routine recommended doses.

    High risk measles – require 2 doses in 2 subsequent days

    Xerophthalmia – 3 doses are given, 1st dose at diagnosis, 2nd the next day and 3rd dose after 2 weeks

Vitamin A Overdose:

The metabolism of plant sources of Vitamin A is highly regulated, so too much intake from dietary sources is very unlikely to cause toxicity. However, excess dietary intake from plant sources can cause yellowing of the skin called carotenemia but will not develop a toxicity.

Acute toxicity – In adults, acute toxicity develops when a single dose of >660,000 IU (>200,000 mcg) of retinol is ingested. Symptoms of acute toxicity include nausea, vomiting, loss of appetite, abdominal pain, dizziness, irritability, drowsiness, raised intra cranial pressure due to cerebral oedema, headache, desquamation, coma or even death [35].

Chronic toxicity usually occurs due to long-term injection of vitamin A which is more than 10 times the RDA [31]. The toxic effects include hepatomegaly, splenomegaly, severe headache, pseudo tumor cerebri, hair changes, alopecia, dry rough cracked skin, and lips, general weakness, arthralgia, hyperostosis of the bone and fractures by minor trauma. In children the signs and symptoms may be slightly different. It includes irritability, drowsiness, delirium, raised intra cranial pressure, bulging fontanelles, psychiatric changes, bulging eyeball, visual disturbances, skin desquamation etc. [35, 36].

Effects on bone – Another risk associated with vitamin A rich diet is the risk of fractures and osteopenia. Several studies conducted by nurses have shown that a diet high in carotenoids is associated with increased risk of fractures in post-menopausal women, and it accelerates osteoporosis [28, 29, 30, 32].

Teratogenicity – In pregnancy, higher doses can result in congenital anomalies due to the teratogenicity of vitamin A. At recommended doses, they are not teratogenic. Consumption exceeding 10,000 IU of preformed vitamin A per day during 1st trimester has caused genetic malformations [27]. The birth defects include encephalitis, microcephaly, craniofacial malformation like cleft palate, cardiovascular abnormalities including transposition of great vessels and thymus abnormalities [36].

Treatment if Vitamin A Overdose

Overdose or toxicity is treated by stopping the use of vitamin A supplements. Generally, the symptoms and signs will subside gradually in a few weeks depending on the severity. However, birth defects caused by the teratogenic effects are irreversible.

Vitamin A and Cancer:

The association between vitamin A and different types of cancers is controversial. It has shown to reduce the risk of certain cancers whereas increasing the risk of other cancers.

  1. Lung Cancer

    Studies have shown that supplementation with carotenoids can increase the risk of lung cancer in men with other risk factors like smoking or asbestos exposure [18, 19].

  2. Prostate Cancer

    Beta carotene supplementation in certain studies have shown an increase in mortality in the study population [20]. However, another study has shown an increase in survival of patients who took beta carotene [21].

  3. Colorectal cancer
    In a study conducted in 864 patients by supplementing antioxidants including vitamin A, no association was found between incidence of colorectal adenoma and cancer reduction [22].
  4. Breast Cancer

    The results of studies related with breast cancer and vitamin A intake is mixed. A study conducted among postmenopausal Iowa women concluded no association between breast cancer and vitamin A intake [23]. However, multiple other studies conducted among premenopausal women suggests that intake of vitamin A reduces the risk of breast cancer, and a diet low in vitamin A increases the susceptibility for breast cancer [24, 25, 26].

    The inconsistent results between different studies and trials relating to vitamin A and cancer is owing to confounding factors like exposure to other risk factors like tobacco in many cancers.

Vitamin A and COVID-19:

The data to comment on the effectiveness of vitamin A in COVID-19 treatment and prevention is limited. However, several clinical trials have been conducted in intensive care settings and have developed several hypotheses in support of the regular use of vitamin A and other antioxidants. These studies have shown that Vitamin A, due to its antioxidant effects, immune function, role in natural barriers and the local paracrine signaling, have been effective in acute respiratory distress syndrome (ARDS) and COVID-19 [33]. Another study has also shown that Vitamin A is effective in treatment of pneumonia which makes it a good treatment option for COVID-19 [34].


Vitamin A is a fat-soluble micronutrient with antioxidant properties. Even after being available in abundance, certain countries are still endemic for vitamin A deficiency. Some develop toxicity due to excessive ingestion, the worst being teratogenic effects. Vitamin A is also used in treatment of different diseases including COVID-19. Vitamin A is a micronutrient with an abundant research scope in the future. Due to the endemicity of vitamin A in certain countries, research on modifying gut bacteria to synthesize vitamin A in risk groups instead of biofortification can better manage the deficiency [44]. As the cancer and vitamin A is always a study with debates, the research on epigenetic role of vitamin A in cancer would have wide scope in the near future [5]. Vitamin A will continue to intrigue the scientific community resulting in an increase in research to further understand and develop the existing knowledge base for this nutrient.


  1. Johnson EJ, Russell RM. Beta-Carotene. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:115-20.
  2. Ross CA. Vitamin A. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:778-91.
  3. Institute of Medicine: Food and Nutrition Board. (2001). Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washingto, DC:The National Academies Press, 82-162.
  4. de Pee, S., & Dary, O. (2002). Biochemical Indicators of Vitamin A Deficiency: Serum Retinol and Serum Retinol Binding Protein. The Journal Of Nutrition, 132(9), 2895S-2901S.
  5. Bar-El Dadon, S., & Reifen, R. (2015). Vitamin A and the epigenome. Critical Reviews In Food Science And Nutrition, 57(11), 2404-2411.
  6. Darlow, B., & Graham, P. (2007). Vitamin A supplementation to prevent mortality and short and long-term morbidity in very low birthweight infants. Cochrane Database Of Systematic Reviews.
  7. Oliveira-Menegozzo, J., Bergamaschi, D., Middleton, P., & East, C. (2010). Vitamin A supplementation for postpartum women. Cochrane Database Of Systematic Reviews.
  8. World Health Organization [u.a.]. (1995). Global prevalence of vitamin A deficiency.
  9. Borowitz, D., Baker, R., & Stallings, V. (2002). Consensus Report on Nutrition for Pediatric Patients With Cystic Fibrosis. Journal Of Pediatric Gastroenterology And Nutrition, 35(3), 246-259.
  10. Leo, M., & Lieber, C. (1999). Alcohol, vitamin A, and β-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. The American Journal Of Clinical Nutrition, 69(6), 1071-1085.
  11. Zalesin, K., Miller, W., Franklin, B., Mudugal, D., Rao Buragadda, A., & Boura, J. et al. (2011). Vitamin A Deficiency after Gastric Bypass Surgery: An Underreported Postoperative Complication. Journal Of Obesity, 2011, 1-4.
  12. Kushner, R., Herron, D., Herrington, H., Jones, D., & Chen, W. (2021). Bariatric surgery: Postoperative nutritional management. UpToDate. Retrieved 22 August 2021, from
  13. UNICEF. Coverage at a Crossroads: New directions for vitamin A supplementation programmes. New York: UNICEF; 2018. Available at: UNICEF. Coverage at a Crossroads: New directions for vitamin A supplementation programmes. New York: UNICEF; 2018.
  14. World Health Organization. Global Prevalence of Vitamin A Deficiency in Populations at Risk 1995–2005: WHO Global Database on Vitamin A Deficiency . Geneva: World Health Organization; 2009
  15. Vivekananthan, D., Penn, M., Sapp, S., Hsu, A., & Topol, E. (2003). Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. The Lancet, 361(9374), 2017-2023.
  16. Araki, S., Kato, S., Namba, F., & Ota, E. (2018). Vitamin A to prevent bronchopulmonary dysplasia in extremely low birth weight infants: a systematic review and meta-analysis. PLOS ONE, 13(11), e0207730.
  17. Age-Related Eye Disease Study Research Group (2001). A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Archives of ophthalmology (Chicago, Ill. : 1960), 119(10), 1417–1436.
  18. Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens, F. L., Valanis, B., Williams, J. H., Barnhart, S., & Hammar, S. (1996). Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. The New England journal of medicine, 334(18), 1150–1155.
  19. Virtamo, J., Pietinen, P., Huttunen, J. K., Korhonen, P., Malila, N., Virtanen, M. J., Albanes, D., Taylor, P. R., Albert, P., & ATBC Study Group (2003). Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA, 290(4), 476–485.
  20. Neuhouser, M. L., Barnett, M. J., Kristal, A. R., Ambrosone, C. B., King, I. B., Thornquist, M., & Goodman, G. G. (2009). Dietary supplement use and prostate cancer risk in the Carotene and Retinol Efficacy Trial. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 18(8), 2202–2206.
  21. Watters, J. L., Gail, M. H., Weinstein, S. J., Virtamo, J., & Albanes, D. (2009). Associations between alpha-tocopherol, beta-carotene, and retinol and prostate cancer survival. Cancer research, 69(9), 3833–3841.
  22. Greenberg, E. R., Baron, J. A., Tosteson, T. D., Freeman, D. H., Jr, Beck, G. J., Bond, J. H., Colacchio, T. A., Coller, J. A., Frankl, H. D., & Haile, R. W. (1994). A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. The New England journal of medicine, 331(3), 141–147.
  23.  Kushi, L. H., Fee, R. M., Sellers, T. A., Zheng, W., & Folsom, A. R. (1996). Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women’s Health Study. American journal of epidemiology, 144(2), 165–174.
  24. Hunter, D. J., Manson, J. E., Colditz, G. A., Stampfer, M. J., Rosner, B., Hennekens, C. H., Speizer, F. E., & Willett, W. C. (1993). A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. The New England journal of medicine, 329(4), 234–240.
  25. Zhang, S., Hunter, D. J., Forman, M. R., Rosner, B. A., Speizer, F. E., Colditz, G. A., Manson, J. E., Hankinson, S. E., & Willett, W. C. (1999). Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. Journal of the National Cancer Institute, 91(6), 547–556.
  26. Tamimi, R. M., Hankinson, S. E., Campos, H., Spiegelman, D., Zhang, S., Colditz, G. A., Willett, W. C., & Hunter, D. J. (2005). Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. American journal of epidemiology, 161(2), 153–160.
  27. Rothman, K. J., Moore, L. L., Singer, M. R., Nguyen, U. S., Mannino, S., & Milunsky, A. (1995). Teratogenicity of high vitamin A intake. The New England journal of medicine, 333(21), 1369–1373.
  28.  Melhus, H., Michaëlsson, K., Kindmark, A., Bergström, R., Holmberg, L., Mallmin, H., Wolk, A., & Ljunghall, S. (1998). Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Annals of internal medicine, 129(10), 770–778.
  29. Feskanich, D., Singh, V., Willett, W. C., & Colditz, G. A. (2002). Vitamin A intake and hip fractures among postmenopausal women. JAMA, 287(1), 47–54.
  30. Michaëlsson, K., Lithell, H., Vessby, B., & Melhus, H. (2003). Serum retinol levels and the risk of fracture. The New England journal of medicine, 348(4), 287–294.
  31. Myhre, A. M., Carlsen, M. H., Bøhn, S. K., Wold, H. L., Laake, P., & Blomhoff, R. (2003). Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations. The American journal of clinical nutrition, 78(6), 1152–1159.
  32. Penniston, K. L., & Tanumihardjo, S. A. (2006). The acute and chronic toxic effects of vitamin A. The American journal of clinical nutrition, 83(2), 191–201.
  33. ‘Jovic, T. H., Ali, S. R., Ibrahim, N., Jessop, Z. M., Tarassoli, S. P., Dobbs, T. D., Holford, P., Thornton, C. A., & Whitaker, I. S. (2020). Could Vitamins Help in the Fight Against COVID-19?. Nutrients, 12(9), 2550.
  34.  Li, R., Wu, K., Li, Y., Liang, X., Tse, W., Yang, L., & Lai, K. P. (2020). Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19. Aging, 12(15), 15784–15796.
  35. Pazirandeh, S., Burns, D., Seres, D., Motil, K., & Kunins, L. (2021). Overview of Vitamin A. UpToDate. Retrieved 23 August 2021, from
  36. Wu, B., & Oakley, A. (2015). Vitamin A toxicity. DermNet NZ: All About Skin. Retrieved 22 August 2021, from,or%20desquamation%20%28peeling%20skin%29%204%20Coma%20and%20death.
  37. World Health Organization Guideline: Vitamin A supplementation for infants and children 6-59 months of age (2011). Available at:
  38. Zile, M. H., & Cullum, M. E. (1983). The Function of Vitamin A: Current Concepts. Proceedings of the Society for Experimental Biology and Medicine, 172(2), 139–152.
  39. U.S. Department of Agriculture (USDA), Agricultural Research Service. FoodData Central: Foundation Foods. Version Current: April 2021.
  40. Booth, S., Johns, T., & Kuhnlein, H. (1992). Natural Food Sources of Vitamin A and Provitamin A. Food And Nutrition Bulletin, 14(1), 1-15.
  41. Huiming, Y., Chaomin, W., & Meng, M. (2005). Vitamin A for treating measles in children. The Cochrane database of systematic reviews, 2005(4), CD001479.
  42. Orfanos, C. E., Zouboulis, C. C., Almond-Roesler, B., & Geilen, C. C. (1997). Current use and future potential role of retinoids in dermatology. Drugs, 53(3), 358–388.
  43. Chomienne, C., Fenaux, P., & Degos, L. (1996). Retinoid differentiation therapy in promyelocytic leukemia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 10(9), 1025–1030.
  44. Srinivasan, K., & Buys, E. (2019). Insights into the role of bacteria in vitamin A biosynthesis: Future research opportunities. Critical Reviews In Food Science And Nutrition, 59(19), 3211-3226.