Micronutrient Deficiencies: Vitamin A And E , Fat Soluble Vitamins

Vitamin A: Retinol

Retinol is the common name for vitamin A.  It consists of a single vitamin and a collection of substances having related functions.  A class of fat-soluble substances that function similarly to all-trans retinol.

Forms of Vitamin A 

The most bioactive form of retinoic acid is thought to be all-trans, which is involved in several functions, including the preservation of the epithelial cell barrier. Trans-retinoic acid regulates gene expression and cell differentiation, which are more important processes. 

Another way to write it is ATRA. This variant, known as 11-cis-retinal, affects eyesight. It is in charge of the production of pigments. The pigments are called rhodopsin and iodopsin. Rod cells contain a pigment called rhodopsin.  Rod cells are involved in seeing in low light. Cone cells contain a pigment called iodopsins. Cone cells are involved in the perception of color.

The condition known as night blindness is brought on by a lack of rhodopsin.  The development of vision, especially dark adaption, and the operation of dark vision depend on 11-cis retina. Both of these substances contain 11-cis-retinal.  Beta-carotene, alpha-carotene, and beta-cryptoxanthin are examples of provitamin A carotenoids. 

The main source of beta-carotene is found in green, leafy foods.  Grapefruits, oranges, and guava all contain alpha-carotene and beta-cryptoxanthin. Compared to beta-carotene, they have lower levels of activity.  Retinyl ester, such as retinyl palmitate, is a type of preformed vitamin A.  When vitamin A is stored in animal tissues, especially in the liver and kidney, it takes the form of retinyl esters. 

Absorption, Biosynthesis, and Excretion of Vitamin A

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There are two types of dietary forms.  Beta-carotene and provitamin A carotenoids; Preformed vitamin A.  These esters hydrolyze when preformed vitamin A is ingested, releasing the retinol molecule.  Retinal can be reduced to retinol through the process of oxidation, which turns it into the aldehyde molecule known as retinal.  Enterocytes, or intestinal epithelial cells, absorb beta-carotene.  Beta-carotene monooxygenase is an enzyme found in intestinal epithelial cells.

 This enzyme is responsible for cleaving beta-carotene and producing retinal. The type that is subsequently released into the bloodstream is retinal. Retinal can undergo further oxidation to produce retinoic acid.
Oxidized metabolites can be produced by retinoic acid.  RA can produce deactivation products during conjugation, which leads to its excretion. 

When retinol levels are too high, it will be esterified and stored as retinal esters.  The primary location in hepatic stellate cells where retinoid esters (RE) are stored. This is where most of the vitamin A is kept.
This is integrated into chylomicrons, which enter the circulation.

Physiological Functions of Vitamin A

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The 11-cis retina is essential to vision.  In a rod cell, opsin, a protein, and 11-cis retina combine to make RHODOPSINS, a dark pigment.
Rhodopsin cleaves whenever a photon strikes it while there is light.
Opsin + all-trans-retinal, the result of this cleavage, generates a neural signal that is interpreted as vision.  The conversion of all-trans-retinal to all-trans-retinol occurs. 

The retinal pigment epithelium absorbs all-trans-retinol (RPE cell).  The regeneration of 11-cis-retinal, which eventually combines with opsin to form the rhodopsin pigment, is mediated by retinal pigmentary epithelial cells, which are closely related to each other. The entire process is disrupted in the event of a vitamin A deficiency, resulting in impaired vision, primarily in the dark. 

Other Functions

Gene expression and tissue differentiation are two specific roles that all-trans retinoic acid plays in the body. It binds to RAR and RXR, two different subtypes of nuclear retinoid receptors.

Miscellaneous Functions 

Additionally, it plays a role in glycoprotein synthesis, immunological function enhancement, and epithelial cell integrity, especially in the GIT and respiratory tract. 

Sources of Vitamin A 

The majority of the sources are foods with animal origins.  Animal products such as beef, liver, and kidney typically contain vitamin A.  The eggs also contain a tiny quantity of vitamin A.  Green leafy greens, including spinach, broccoli, and other similar vegetables, are a source of certain plant origins.  They can also be found in yellow vegetables like pumpkins and yellow fruits like papaya and guava.  Carotenoids and their derivatives are the primary forms in which it manifests.  Fish and cod liver oil were also discovered. 

RDA of Vitamin A

Recommended Dietary Alliance is what RDA stands for.  Age is a major factor in RDA.. Retinol Activity Equivalent, or RAE, is equal to one microgram of retinol
• The recommended daily allowance (RDA) is 350 micrograms for children ages 0 to 12.
• The recommended daily allowance (RDA) is 390 micrograms for children ages 1 to 3.
• The recommended daily allowance (RDA) is 510 micrograms for children ages 4 to 6.
• The recommended daily allowance (RDA) is 630 micrograms for children aged 7 to 9.
• The recommended daily allowance (RDA) for boys and girls between the ages of 10 and 12 is 770 and 790 micrograms, respectively.
• 3.3 international units (IU) of vitamin A are equal to 1 microgram of retinol.

Risk Factors Increasing Vitamin A Deficiency Risk 

Vitamin A absorption will be impacted in the event of malabsorption.
Conditions known as malabsorptive conditions, such as inflammatory bowel disease and celiac disease, are linked to a higher risk of vitamin A.  Because vitamin A stores are reported to be limited in liver illness, there is also a correlation between liver disease and vitamin A deficiency such as marasmus and kwashiorkor, which are cases of protein energy deficiency.  Low food consumption will lead to a reduction in vitamin A insufficiency and a decrease in protein intake, which will reduce the synthesis of RBP (retinol binding protein). 

Although retinol-binding proteins bind the retinol protein, they are not single proteins; retinol protein alone is insufficient to transport vitamin A.
To become associated, it needs another protein called transthyretin.
Three complicated forms of vitamin A are delivered into the plasma: transthyretin + RBP + retinol. Since both transthyretin and RBP are proteins, their absence will exacerbate vitamin A deficiencies in malnutrition due to inadequate food intake.  Prolonged zinc consumption interferes with vitamin A absorption in the intestines.  Vitamin A insufficiency can also result from infections such as the measles. 

Clinical Features

 A mild deficiency will result in follicular hyperkeratosis, a clinical characteristic that thickens hair follicles and deposits keratin, giving the appearance of "goosebumps."  A reduction in epithelial integrity  A greater risk of diarrheal infection is associated with vitamin A deficiency.  A loss of epithelial integrity in the GIT will result in an increased risk of diarrhea.  Goblet cell functions and numbers are reduced in these patients. 

Epithelial integrity can occur in the urinary bladder, resulting in haematuria and cystitis; • Squamous metaplasia of the renal pelvis, ureters, vaginal epithelium, pancreatic and salivary ducts can cause localized increased infections. • Epithelial integrity can involve the respiratory tract, and there can be an increased risk of respiratory infections, including pneumonia, bronchiectasis, and mastoiditis. 

Ocular Features

Defective or delayed dark adaptation is the first symptom, and it can evolve to noctalopia, or night blindness. Xerophthalmia, or dry eyes, is one of the other characteristics.  It involves the cornea being dry and keratinized. Bitot spots are lesions that appear white, fleshy, or foamy and are generated on the temporal side of the conjunctiva. Additionally, patients may experience keratomalacia and corneal ulcers.  The keratinization of the retinal pigmentary epithelium may potentially be the cause, which can result in blindness. 

Who Classification Of Xerophthalmia And Eye Signs In Vitamin A Deficiency

Diagnosis Of Vitamin A Deficiency

Several diagnosis are possible.
• A test of dark adaptation is possible.
• Ocular exams are performed in order to assess the deficiency.
• A lot of people will exhibit mild leukopenia in the WBC/mm3 range of 2500 to 5000.
• Plasma retinol, which is typically measured at 15 micrograms/dl even though it is not very sensitive.
• There are more than 20 micrograms of vitamin A per gram of liver tissue. 

Treatment

Massive dosages of vitamin A are always administered throughout treatment, usually orally.  The children's ages will determine the dosage. 
•The dosage will be 50,000 IU if the child is younger than six months old.
• The dosage is one lakh IU if the child is between six and twelve months old.
• The dosage will be 2 lakhs IU if the child is older than 12 months.
•The doses will be administered as soon as the diagnosis is made, the following day, and two weeks later. 

 If the kid is younger than six months old and there is a suspected instance of malabsorption with severe deficiency in these individuals, the parental dose—roughly 75% of the oral dose—will be administered.
A parental dose equivalent to roughly 50% of the oral dose will be administered if the child is older than six to twelve months. 

When a child has clouding of the cornea, it is an emergency that needs to be treated right away by their parents with 50,000–100,000 IU of vitamin A. 

 Additional keratomalacia management.- The cushioning of the eyes caused by topical antibiotics and sterile lubricants is known as keratomalacia. 

Prevention Of Vitamin A Deficiency 

 The original recommendation was to administer one megadose every six months to children ages six months to five.
• At nine months of age, a single dose of one lakh IU is often administered.
• The second dose, which is 2 lakh IU, is administered between the ages of 15 and 18 months.
• At 24 months, 30 months, and 36 months, three further doses will be administered. 

Hypervitaminosis A

Because vitamin A is not water soluble and cannot be eliminated from the body, an excess of it might result in hypervitaminosis. It usually occurs in two ways: (1) acute consumption of vitamin A, which is documented in two cases: sailors and those who regularly eat significant amounts of fish liver; (2) acute ingestion of pharmaceutical forms of vitamin A. 

In general, acute ingestion is discovered to be really uncommon.
• The second, and comparatively more frequent, is chronic ingestion.
• Patients who are food faddists experience this.
• Children who ingest more than 6000 mcg per day for several weeks will experience chronic poisoning.
• For a few weeks, when people take more than 15,000 micrograms per day. 

Manifestations Of Hypervitaminosis A 

Acute 

CN palsies, vomiting, enlarged fontanelles, and diplopia are symptoms of pseudotumor cerebri.

Chronic 

The early warning signals will include nausea and vomiting.  Following that, the patients would experience alopecia, lost hair, irritability, and anorexia.  Other signs and symptoms include dry mucosa, skin desquamation, and fissures at the angle of the mouth. 
Hepatosplenomegaly is a significant condition that will cause bony hyperostosis and discomfort in the bones.  Increased stupor and ICP.
Liver cirrhosis and hypercalcemia may occur.

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Also Read: Enteric Infections">Diarrhea In Children: Types Of Enteric Infections

Hypervitaminosis A Shows Significant Hyperostosis

Long bone shaft: Hyperostosis does not develop at the end. It appears at the center of the long bone shaft. Next, we identify vitamins A and teratogenicity. Severe hypervitaminosis, both acute and chronic, has also been linked to mortality. The only vitamin that has been shown to be teratogenic by science is A. 

What Is The Treatment For Hypervitaminosis? 

Since there is no physiological counteragent, supportive therapy is the sole available treatment. If the consumption was acute, supportive therapy is administered, and the patient is gradually released from the hospital based on the body's stored vitamin A.

Vitamin A and Teratogenicity

Therapeutic dosages of oral 13-cis retinoic acid (0.5–1.5 mg/kg) during the first trimester of pregnancy have been linked to teratogenicity.
They will have cleft lips and palates as a manifestation of craniofacial malformations involving the CNS. They will also be more likely to experience neural tube defects and occasionally exhibit brain neuronal migration issues. 

Thymic aplasia case reports are quite rare. According to WHO guidelines, pregnant women should not consume more than 3000 micrograms of vitamin A per day or 7500 micrograms per week.

Carotenemia - A Benign Entity

 Beta-carotene levels in the blood are increased in beta-caroteneemia, a benign pediatric illness that frequently causes skin yellowing.  One significant and common precursor of vitamin A is beta-carotene.  Overindulgence in foods high in beta-carotene, such as carrots, can lead to accumulation and the development of clinical characteristics. 

The term "carotenemia" refers to elevated plasma levels.  Calorotenoid cutaneous discoloration is the term for yellowish discoloration of the skin, such as the palms and soles.  Typically, children with DM, liver illness, and hypothyroidism are more likely to experience it.  After quitting excess consumption, it returns in two to six weeks.  Patients do not experience any significant toxicity. 

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What Are The Manifestations That Will Happen In These? 

Craniofacial anomalies will be present in these patients. As a result, they will suffer facial and central nervous system abnormalities. They will either have a cleft palate or lip. There will be a higher chance of neural tube abnormalities for them. They occasionally might also display Brain.

Extra Edge Stuff: Inflammation and Vitamin A Deficiency

Vitamin A deficient features are primarily developed in patients with acute inflammation, such as measles, and chronic inflammation, such as cystic fibrosis. Patients with these disorders are treated when vitamin A supplementation is administered. 

Supplementing with vitamin A occasionally yields no results. This occurs as a result of markedly lower levels of RBP and transthyretin in patients who are in an inflammatory state.  For these patients, reducing inflammation is the main priority.  Parenteral supplementation has been demonstrated to be superior to oral supplementation.  For these people, little, frequent dosages are preferable to high, megadoses. 

Vitamin E: Tocopherol

 A set of eight fat-soluble substances that share a structure and strong antioxidant properties, with alpha tocopherol being the most effective type. 

PRIMARY FUNCTION: The plasma membrane's antioxidant activity stops lipid peroxidation.  PUFA stands for polyunsaturated fatty acids.
Vitamin E shields it from oxidation and indirectly lowers the production of free radicals.

Sources of Vitamin E

Both plants and animals have abundant sources of vitamin E.  Corn, cottonseed, safflower, and vegetable oil are the main sources.  Nuts and seeds, particularly walnuts, contain it. Not only is vitamin E prevalent in green leafy vegetables, but it's also found in margarine, milk, eggs, and considerable amounts in breast milk. 

Digestion and Absorption 

• Dietary fats and medium-chain triglycerides improve absorption.
• Bile and pancreatic juice facilitate vitamin E absorption.
• Translocated as chylomicrons from the intestines to the liver.
• Moved from the liver into tissues via RBCs and as a component of LDL.

RDA of Vitamin E 

The RDA 2020 states that 0.8 mg/g of dietary EFAs are needed.
• For adults, that equates to 7.5–10 mg daily.
• Typically, infants need (non-FDA) infancy: 1-3 mg/day or 0.4 microgram/kg/day.
• Doses ranging from 3 to 6 mg per day are necessary for older children. 

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Vitamin E deficiency Risk is Increased in? 

Even in the last trimester, it occurs at its peak around 34 to 36 weeks. PRETERM BABIES: typically have a limited reserve of vitamin E in their bodies, and the maternal transfer of vitamin E in utero occurs during this time.  A child's risk of developing a vitamin E deficit is increased if they are not getting their mother's milk; any child born before 34 weeks of pregnancy will already have less vitamin E. 

 High PUFA but low vitamin E formula milk causes an imbalance that inhibits lipid peroxidation and, once more, results in vitamin E deficiency.
Prolonged cholestasis and oral iron supplements will result in fat malabsorption.  Malnutrition due to insufficient intake of all micronutrients in protein efficiency.  A vitamin E deficiency is linked to the fat malabsorption condition known as abetalipoproteinemia. 

Clinical Features

Preterm infants are known to have hemolytic anemia, which peaks in the second week of life.  In older children, the nervous system, muscles, and central nervous system are typically involved in the manifestation.  Abnormalities of the posterior column, loss of DTRs, progressive peripheral neuropathy, and cerebral ataxia. 

 Myopathy and muscle weakness are more common in elderly individuals; in young children, they are typically minor.  It is possible for segmentary retinopathy to cause ocular involvement. Paralysis of the eye's extrinsic muscles is known as ophthalmoplegia.

Also Read: Marfan Syndrome : Signs, Diagnosis, Management and Prognosis

Diagnosis of Vit E Deficiency

There's a chance that the circulating level is unnaturally low.  The patient's changed consumption of fat may be connected to this.  The easiest way to find out is to measure the vitamin E to serum lipid ratio. 
• In infants, a vitamin E deficit may be indicated if the ratio is less than 0.6 mg/g.
• In older kids: less than 0.8 mg/g may indicate a vitamin E deficit.
There may be some thrombocytosis in preterm infants, especially in those with hemolytic anemia. In premature infants exhibiting atypical nerve conduction velocities and Evoked Potentials in individuals suffering from neurological disorders.

Treatment

The RDAs for vitamin E are debatable, but the course of treatment is set in stone.  Neonates receive 25–50 units per day for one week, after which they must consume a sufficient diet.  Children with malabsorption-related deficiencies should get 1 unit/kg per day.

Extra Edge Topics: AVED 

 Isolated vitamin E insufficiency accompanied by ataxia.  Alpha-tocopherol transport into lipoproteins is compromised in the AR disease due to a mutation in the TTPA gene.  Low blood levels of vitamin E in the serum.  It's typical for the intestines to absorb.  Lifelong high-dose vitamin E supplementation is required.

Always rule out vitamin E insufficiency in children with ataxia symptoms for which there is no known explanation and malabsorption may or may not be present.

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