Vitamin A and Nutrition

Lorenzo Cervantes BS

Janine Smith, MD

SUNY-Downstate medical Center

Department of Ophthamology

PRE-TEST

Q1. A five-year old boy complains of loss of night vision, drying of the conjunctiva, dry and scaly skin, and loss of hair. The boy's ocular complaints are some of the symptoms of:

A. Beriberi

B. Scurvy

C. Xerophthalmia

D. Pellagra

Q2. Which of the following nutrients are needed for proper distribution of vitamin A to tissues?

A. Protein and iron

B. Protein and zinc

C. Protein and copper

D. Protein and nickel

Q3. A seven-year old girl presents with fever, cough, conjunctivitis, cervical lymphadenopathy, splenomegaly, and maculo-papular rash that began at her head and spread to the rest of her body. Serum levels of which of the following would be increased?

A. C-reactive protein

B. Retinol

C. Retinol binding protein

D. Retinal

Q4. One serving (amount) of which of the following would provide the most vitamin A?

A. Fat free milk, fortified with vitamin A (1 cup)

B. Whole milk (1 cup)

C. Peas, frozen, boiled (1/2 cup)

D. Cantaloupe, raw (1 cup)

E. Oatmeal, instant, fortified, plain, prepared with water (1 packet)

Q5. Which of the following is the form of vitamin A derived from animal foods?

A. Retinol

B. Alpha-carotene

C. Beta-carotene

D. B-cryptoxanthin

E. Lycopene

OBJECTIVES:

On completion of this module, residents and physicians will be able to:

1. Gain an appreciation for the importance of vitamin A and its effects on the morbidity and mortality of children.

2. Gain an understanding of vitamin A metabolism.

3. Gain an understanding of the assessment of vitamin A status.

4. Recognize the clinical manifestations of xerophthalmia.

5. Recognize populations at increased risk for developing vitamin A deficiency.

FACILITATOR PREPARATION:

The facilitator should review the article by:

Smith J and Steinemann TL, Vitamin A Deficiency and the Eye (Int Ophthalmol Clin. 2000 Fall;40(4):83-91). The case study is based on a case report by Fiore P, De Marco R, Sacco O, Priolo E, Nightblindness, Xerophthalmia, and Severe Loss of Visual Acuity due to Unnecessary Dietary Restriction (Nutrition. 2004 May;20(5):477).

Other interesting case reports include Jaworowski S, Drabkin E, Rozenman Y. Xerophthalmia and undiagnosed eating disorder (Psychosomatics. 2002 Nov-Dec;43(6):506-7.) and Ramsay A, Sabrosa NA, Pavesio CE. Bitot's spots and vitamin A deficiency in a child from the UK (Br J Ophthalmol. 2001 Mar;85(3):372.).

A detailed explanation of the physiology and metabolism of vitamin A can be found in almost any medical physiology textbook. Information provided here was from Guyton AC and Hall JE. (eds) Textbook of Medical Physiology, Ninth edition. W.B. Saunders Company, Philadelphia, PA. 1996.

A standard reference for Vitamin A is Ross AC. Vitamin A (in) Modern Nutrition in health and Disease, 9th and 10th editions Shils ME, Ross AC, Olson R, Shike M. Lippincott Williams ansd Wilins. Baltimore. 1999 and in press.

See "References" listed at the end of the module for a comprehensive review of this subject.

INTRODUCTION

The subject of nutrition and its effects on the eye covers many topics. In the adult, areas of interest include the impact of antioxidants - such as vitamins A, C, and E - on the prevention of age-related eye diseases; nutritional optic neuropathies of single or multiple nutritional deficiencies; tear production and lacrimal duct function; and other ocular diseases where there has been some evidence for nutritional therapies {Congdon}

In the child, however, the area of greatest concern is in vitamin A deficiency and its effects on vision loss. Vitamin A deficiency is the leading cause of preventable blindness in children. Between 100 and 140 million children are vitamin A deficient worldwide. It is a public health problem in 118 countries, especially in Africa and South-East Asia. An estimated 250 to 500 thousand vitamin A-deficient children become blind every year, with half of them dying within one year of losing their sight {from the WHO website, Combating Vitamin A Deficiency}.

Vitamin A deficiency is common in the developing world. It is the cause of a group of ocular signs known as xerophthalmia. The earliest symptom is night blindness, which is followed by drying of first the conjunctiva, then the cornea. Progression of disease includes keratomalacia, ulceration, perforation and scarring of the cornea, and blindness. Vitamin A also has a profound effect on morbidity and mortality, even in the absence of ocular signs {Underwood}. Many controlled trials have shown that improvement of vitamin A status of children aged six months to six years in vitamin A deficient populations can alone reduce mortality rates by up to 54% {Congdon, Congdon references 27-34}, particularly in those with measles and diarrhea. Giving vitamin A to pregnant women may reduce maternal mortality related to pregnancy by nearly 50% {Congdon reference 35}, while also reducing mother-to-child transmission of HIV-1 {Congdon reference 36}

CASE STUDY PART 1

Andrew is an eight-year old Chinese-American boy brought to clinic by his mother because he is complaining that he "has something in his eye." According to his mother, this sensation is located on the surface of both eyes, has persisted for the past two months, and is not associated with any tearing or discharge. She had tried placing over-the-counter saline drops in the eyes, but to no relief. Mrs. A also states that he began wetting his bed three months ago because he is afraid to get out of bed at night to use the bathroom. He confirms this, saying that he cannot see at night.

Andrew had no significant past medical history, was taking no medications, and had no known drug allergies. His mother states that he has allergies to foods, but does recall which ones. Inquiry to the diet reveals that Andrew has been on a restricted diet, imposed by his family for several years, because of fear of his food allergies. His diet consists mostly of bread, hard wheat pastas, rice, small servings of white meat, and olive oil. He does not consume any milk or dairy products, fish, eggs, fruits, or vegetables.

Q1. What sorts of nutritional deficiencies is Andrew at risk of developing?

Andrew's imposed diet that restricts fruits, vegetables, and most animal products puts him at risk of developing numerous nutritional deficiencies. Protein, iron, calcium, vitamin B12, zinc, vitamin A, and vitamin D are a few of the nutrients he may be lacking. His current diet is similar to many southeast Asian diets that consist of mainly rice and not much else. In fact, many people in that area and around the world present with similar symptoms as Andrew, due to deficiency in vitamin A.

Q2. What role does vitamin A play in the eye?

Vitamin A is a fat-soluble vitamin ingested in the diet in two forms: retinol, found in animal sources like milk, meat, fish, liver, and eggs; and the provitamin carotene, found in plant sources such as green leafy vegetables, yellow fruits, and red palm oil. In the small intestine, carotene is converted to retinol within the epithelial cell and, along with directly ingested retinol, is esterified to palmitic acid (retinyl palmitate). This retinyl palmitate travels via the lymphatics to the liver where it is stored {Smith}.

In times of need, stored retinyl palmitate is converted back to retinol and shuttled in the circulation by retinol binding protein (RBP). Zinc and protein is necessary in the formation of RBP, which is necessary for retinol transport {Smith reference 11}. RBP is also a negative acute phase reactant; its serum concentration is inversely proportional to that of C-reactive protein {Stephensen}. In conditions of inflammation or infection, smaller amounts of RBP are produced by the liver, thereby decreasing the serum retinol concentration and the amount delivered to target tissues.

The eye has two roles for the use of vitamin A. First, in the retina, vitamin A is used as a precursor for the light sensitive pigments of the photoreceptors - the rod and cone cells. These pigments are the bridge between light energy and nerve impulse, a process called phototransduction. Second, vitamin A is necessary for RNA and glycoprotein synthesis in conjunctival epithelial cells in order to maintain the conjunctival mucosa and corneal stroma {Smith}.

Rods and cones are separated into four major functional segments: the outer segment, the inner segment, the nucleus, and the synaptic body. In the outer segment, the light-sensitive photopigments are found, which decompose when exposed to light, leading to excitation of the cells and nerve fibers leaving from the eye. Rods contain one pigment, called rhodopsin. Cones contain three pigments that are similarly structured, but each one responding to a different wavelength of light. Rods are responsible for vision in dim or low light (scotopic vision), and the cones are responsible for color vision and vision in bright light (photopic vision).

Vitamin A is the backbone of the visual pigments, the major difference being the type of protein that is bound to the retinol. In the rods, vitamin A (all-trans-retinol) is converted to 11-cis-retinol and then to 11-cis-retinal. This form of retinal binds with the protein scotopsin to form rhodopsin, the photosensitive pigment found in the outer segment of the rod. Light energy causes rhodopsin to decompose through different configurations until it reaches its activated form, metarhodopsin II.

Metarhodopsin II is the first enzyme of a second messenger amplification cascade that allows a very small amount of light to cause great excitement of the photoreceptor cell. Metarhodopsin II activates numerous molecules of transducin. Transducin activates many molecules of phosphodiesterase. Activated phosphodiesterase hydrolyzes many molecules of cGMP, which are holding open sodium channels in the outer membrane, keeping the photoreceptor in a depolarized state. Hydrolyzation and destruction of the cGMP causes the sodium channel to close, reducing sodium membrane conductance and causing a hyperpolarization of the cell. This translates to excitation of the visual nerve fibers leaving the eye. Within a second of activation, metarhodopsin II is decomposed to all-trans-retinal and scotopsin, allowing the photoreceptors back to their depolarized state. All-trans-retinal must be reconfigured to the 11-cis-retinal formation in order to recombine with scotopsin to form rhodopsin. However, there is always some retinal lost. Without a constant source of vitamin A, retinal depletes, preventing the formation of rhodopsin and the event of phototransduction.

FIGURE 1. THE NEED FOR VITAMIN A IN THE EYE (THE MANY FORMS OF VITAMIN A)

CAPTION: Serum retinol is in the all-trans configuration and is converted to the cis-configuration in the retina by an isomerase. This form is converted to the aldehyde form 11-cis retinal, which then binds with scotopsin to form rhodopsin, the photopigment in rod cells. Light energy causes rhodopsin to decompose to an activated form (metarhodopsin II) which sets off the cascade leading to visual signal transmission.

Q3. How can we assess Andrew's vitamin A status?

The gold standard of assessing Andrew's vitamin A status is to take a liver biopsy to determine reserve stores. Since such a procedure is not feasible or justifiable in most cases, other methods have been developed to reflect the compartment.

Traditionally, clinical signs and symptoms of xerophthalmia were used to identify vitamin A deficiency {Tanumihardjo}.

Stages of Vitamin A Deficiency Seen in the Eye

Thus, the simplest, cheapest, and most practical way of diagnosing suspected deficiency with clinical signs would be to treat Andrew with vitamin A supplementation (see below for treatment). In other cases of suspected vitamin A deficiency without symptoms, however, it may be necessary to assess a patient's status by other means. This is due to the revision of the definition of vitamin A deficiency in the 1990s to include subclinical deficiency.

Serum retinol concentrations are commonly used to identify deficiency. However, serum retinol levels are homeostatically controlled and do not begin to decline until liver reserves fall drastically. Serum total and holo-retinol binding protein (the complex of vitamin A and RBP) is also measured {Smith}. However, since retinol can only circulate bound to retinol binding protein, any condition leading to decreased levels of RBP, like protein deficiency, can falsely show low vitamin A stores. For example, RBP is a negative acute phase reactant and decreases during an infection or systemic inflammatory response {Tanumihardjo}.

Breast milk retinol concentration measurement is less invasive than blood drawing. Such a measure is useful because the reading from the mother can be predictive of the status of the nursing infant {Tanumihardjo reference 14}.

Conjunctival impression cytology is another test used. A small circular piece of filter paper is touched to the eye surface, fixated, stained, and visualized under microscopy. Goblet cells are differentiated from endothelial cells and counted, with normal or abnormal results based on the number of goblet cells present {Tanumihardjo}.

CASE STUDY PART 2

On physical exam, Andrew's vital signs are stable and his weight and height are both in the 25th-50th percentile. Ocular exam shows decreases in visual acuity bilaterally; conjunctival and corneal dryness; and triangular, sandy-like lesions in the temporal paralimbal areas of both eyes. Labs are collected revealing mild anemia with normal MCV, iron, and zinc levels; and decreased levels of serum retinol, retinol-binding protein, folate, and vitamin B12.

Q4. How might Andrew's low levels of retinol and retinol-binding protein account for his symptoms?

Xerophthalmia presents when not enough vitamin A is available for the eye. Clinical manifestations involve the retina, conjunctiva, and cornea. The World Health Organization classified these clinical signs of xerophthalmia, as shown in Table {World Health Organization Reclassification of Xerophthalmia signs, Ocular signs and classifications, Smith reference 21}.

A lack of rhodopsin in rod cells leads to night blindness, the earliest and most common symptom of vitamin A deficiency. Andrew states that he cannot see at night, preventing him from getting out of bed to use the bathroom. Even in subclinical deficiency, electroretinography and dark-adaptation studies can show abnormalities in retinal function {Smith reference 22}.

Andrew's sensation of a foreign object on the eye is a common interpretation caused by drying of and lesion formation on the surface of the eye. Conjunctival xerosis, or drying (X1A), occurs because of a loss of mucous-secreting goblet cells and eventual squamous cell metaplasia of the conjunctival epithelial cells. It is seen as a dry, granular patch that can exhibit thickening, wrinkling, loss of pigmentation, and transparency.

It is typically found on the temporal, interpalpebral, bulbar conjunctiva. {Smith, Smith references 7,23,24}.

Bitot's spots (X1B) are triangular, gray plaques of keratinized conjunctival debris overlying an area of conjunctival xerosis, found around the junction of the cornea and the sclera, or limbus. Individuals who are generally malnourished, but have normal vitamin A levels, may also be found to have these lesions {Smith, Smith references 20,24}.

Corneal xerosis, ulceration, and keratomalacia represent potentially visually disabling corneal changes due to abnormal tear secretion, loss of mucus-producing goblet cells, keratinizing metaplasia, and bacterial superinfection {Congdon, Congdon references 7,10,11,12}. Corneal xerosis (X2) is the earliest corneal manifestation of xerophthalmia. A dull corneal appearance is seen and, under visualization with fluorescein, superficial punctate lesions can be noted. This stage is present in a majority of people who exhibit night blindness and Bitot's spots. Without treatment, it progresses to epithelial defects, stromal edema, and keratinization in the interpalpebral fissure. It presents almost always bilaterally {Smith}.

Corneal ulceration (X3) results from the progression of the corneal epithelial defects. Characteristically, these ulcers are small, located nasally on the cornea, and have sharp borders. They can be partial or full thickness. Complications include secondary bacterial infection and obstruction of light entering through the pupil {Smith reference 24}. Keratomalacia is a full-thickness liquefactive necrosis of the cornea, presenting as a sharply demarcated lesion with an opaque grayish yellow appearance. Sloughing of the corneal stroma can lead to either a bulging of the innermost basement membrane, called a descemetocele, or in perforation and loss of the anterior chamber. Studies of vitamin-deficient animals suggest that keratomalacia may not be caused by vitamin A deficiency alone {Smith reference 25}. It is often associated with a preceding systemic stressor, such as measles, diarrhea, respiratory infection, or severe protein-energy malnutrition {Smith}. Corneal scarring (XS) is the result of severe stromal loss during keratomalacia {Congdon}

Fundal changes in xerophthalmia (XF) are described as yellow and white dots in the retinal periphery, representing focal retinal pigment epithelium defects {Smith, Smith reference 26}. They may rarely be associated with defects in the visual field {Smith reference 27}.

Systemic manifestations may occur because of the necessity of vitamin A for normal growth and proliferation of the different types of epithelial cells. Deficiency leads to stratification and keratinization of epithelial structures, often leading to infection of the conjunctiva, urinary tract, and respiratory passages, for example {Guyton}.

CASE STUDY PART 3

Based on the clinical presentation and decreased serum retinol level, the diagnosis of xerophthalmia is made in Andrew.

Q5. What is the immediate treatment of choice for Andrew's xerophthalmia?

The various forms of xerophthalmia present in Andrew are rapidly reversible with timely vitamin A treatment {Congdon}. When keratomalacia has progressed to almost total melt of the entire cornea, however, vitamin A treatment has virtually no effect {Rodrigues}. Once night blindness develops, it can be reversed in as little as one hour {Guyton}, but will usually respond within a day or two after systemic administration of vitamin A. Bitot spots and drying of the eye also resolve after vitamin A supplementation. Corneal epithelial defects may take more time to heal, but vitamin A supplementation will speed the healing process. Visual field defects associated with xerophthalmic fundus disappear within 1-2 weeks after supplementation, and the retinal spots fading after about 1-4 months {Smith}.

Replenishment of vitamin A stores is the goal of therapy. The oral dosage regimen suggested for Andrew is 200,000 IU of vitamin A in oil followed the next day and in two weeks with an additional dose of 200,000 IU {Smith reference 23}. Children with concurrent severe protein deficiency should receive an additional oral dose every two weeks until their protein status improves {Smith reference 33}. If patients have severe corneal disease or malabsorption, the preferable dose is 100,000 IU water-miscible vitamin A intramuscularly {Smith reference 34}.

FIGURE 2. DOSING REGIMEN FOR TREATMENT OF VITAMIN A DEFICIENCY [Lexi-Comp Online]

Prophylactic Treatment of Early Stage Deficiency (xerophthalmia without corneal changes):

Oral:

Infants <1 year: 100,000 units every 4-6 months
Children 1-8 years: 200,000 units every 4-6 months
Children >8 years: 100,000 units/day for 3 days then 50,000 units/day for 14 days

Parenteral treatment of deficiency (I.M.):

*Note: I.M. route is indicated when oral administration is not feasible or when absorption is insufficient (e.g. malabsorption syndrome)

Infants: 7500-15,000 units/day for 10 days
Children 1-8 years: 17,500-35,000 units/day for 10 days
Children >8 years: 100,000 units/day for 3 days, followed by 50,000 units/day for 2 weeks

Note: Follow-up therapy with an oral therapeutic multivitamin (containing additional vitamin A) is recommended:

Low Birth Weight Infants - Additional vitamin A is recommended, however, no dosage amount has been established
Children 8 years: 5000-10,000 units/day
Children >8 years: 10,000-20,000 units/day

Surgery plays little role in the treatment of xerophthalmia. Partial-thickness ulcerations of the cornea heal well with nutritional supplementation alone. Full-thickness keratomalacia is often inoperable because the entire cornea is involved and a malnourished patient would be too weak to undergo anesthesia. Corneal transplantation can be used successfully in treatment of scars obstructing the visual axis, but only if visual function is still intact and if the patient's social situation and environment allow survival of the graft {Smith}.

CASE STUDY PART 4

Treatment is started immediately, consisting of an oral dose of 200,000 IU of vitamin A on days one, two, and ten; 10 days of 1000 micrograms of vitamin B12; as well as folic acid and multivitamin supplements.

Q6. What advice would you give to Andrew's family?

The most important issue to address as Andrew's physician is the family's choice of his diet. They are obviously very concerned of a suspected food allergy and have gone to great lengths to prevent an adverse reaction. However, the lack of knowledge of the specific food allergy has led to virtual elimination of fruits, vegetables, and animal products from Andrew's diet. Sending Andrew for allergy testing in order to find the cause of his allergies, if any, can address their concerns. A well balanced diet can then be tailored with targeted, rather than generalized, food exclusion.

Foods with a high content of vitamin should be included in Andrew's diet. The table shown below provides an idea of some foods that accomplish this. Darkly colored fruits and vegetables are excellent sources of beta-carotene, a precursor to vitamin A. A single serving of carrots, sweet potatoes, spinach, mango, or cantaloupe can provide more than a full day's recommended allowance. Animal liver, predictably, provides a great deal of vitamin A. The goal diet should be well balanced and supplemented with multivitamins, so as to replenish Andrew's numerous nutritional deficiencies.

CASE STUDY PART 5

Allergy testing is performed, revealing that Andrew is allergic to only apples and peanuts. A nutritionist prescribes a balanced diet with multivitamin supplements, which the family accepts. A follow up visit in three months shows resolution of Andrew's symptoms, as well as normalization of his labs.

Q7. Where is xerophthalmia and vitamin A deficiency most prevalent?

Xerophthalmia is a problem wherever the combination of vitamin A and protein deficiency exists. Vitamin A deficiency is a worldwide problem, impacting millions of lives, especially in underdeveloped areas of Asia, where the diet often consists of rice and little more {Smith}. In 1995, the World Health Organization redefined vitamin A deficiency to include subclinical levels of deficiency (serum retinol <0.7 micromol/L) {Underwood reference 23}. By the end of the 1990s, 140 - 250 million preschool age children were estimated to be at risk of vitamin A deficiency disorders, including an incidence of 3 million who annually have clinical signs {Underwood reference 24}.

In parts of Africa, some reports suggest a prevalence of xerophthalmia as high as that found in Southeast Asia {Smith references 15-18}. Other parts, particularly West Africa, have a lower prevalence mostly because the red palm oil widely used in cooking is a good source of vitamin A {Smith reference 19}. In Latin America and the Caribbean xerophthalmia is fairly well controlled. Haiti, however, has an incidence as high as that in some countries in Asia {Smith reference 14}. In endemic countries, the prevalence of disease is mainly located in lower socioeconomic groups who cannot afford vitamin A-rich foods.

Q8. What factors would predispose an individual to vitamin A deficiency in a nutritionally adequate area?

In the United States, vitamin A deficiency is a rare condition although some associations exist. In children above the age of 4, serum retinol concentrations are positively associated with greater age, body mass index, serum lipids, and the use of supplements containing vitamin A. The prevalence of lower, but not yet deficient, levels of serum retinol is higher in non-Hispanic black and Mexican American children than in non-Hispanic white children {Ballew}.

Xerophthalmia can affect any age group, but it is most common in children aged 1 to 6 years, with the most severe blinding complications affecting those children aged 6 months to 3 years {Smith}. It has been reported in food faddists and psychiatric patients {Rodrigues reference 1}. However, most of the cases in developed countries are due to alcoholism and conditions causing malabsorption {Rodrigues reference 2}. The incidence is higher in children because, aside from the greater metabolic demand caused by rapid growth and susceptibility to infections, infants of vitamin A-deficient mothers neither have large liver stores of vitamin A nor receive adequate amounts through breastfeeding {Smith reference 20}.

FIGURE 3.Children living in the United States who are considered to be at increased risk for subclinical vitamin A deficiency include [NIH, NIH reference 9]:

Toddlers and preschool age children
Children living at or below the poverty level
Children with inadequate health care or immunizations
Children living in areas with known nutritional deficiencies
Recent immigrants or refugees from developing countries with high incidence of vitamin A deficiency or measles
Children with diseases of the pancreas, liver, intestines, or with inadequate fat digestion/absorption

Q9. How can vitamin A deficiency and its associated diseases be prevented worldwide?

Improving vitamin A status will reduce childhood mortality and the risk of blindness. Prevention relies on the maintenance of adequate vitamin A stores, either by increasing vitamin A intake in the diet or by periodic administration of vitamin A. For prophylaxis in endemically deficient areas, breast-feeding and vitamin A supplementation of both child and nursing mother are recommended. This is of particular importance because mothers who are deficient themselves will not provide adequate nutrition in their breast milk, the only source of vitamin A for nursing infants. Newborns should receive 50,000 IU of vitamin A, children younger than one year should receive 100,000 IU every four to six months, adults and children older than one year should receive 200,000 IU every four to six months, and pregnant or lactating women should receive 20,000 IU each week {Smith, Smith reference 21}.

Much attention was given by international health organizations in the 1990s to fight vitamin A deficiency on a global basis. Many countries distribute high dose vitamin A capsules, which can provide supplementation for four to six months per dose. Twice-yearly micronutrient days, for example, have been established, as well as integration of distribution into routine health programs like immunizations. Food fortification programs have been a successful strategy in industrialized countries {Underwood reference 19} and some countries in mid level development status. Stability and continuity of these programs has truly shown a great impact against vitamin A deficiency. However, recent experiences in Indonesia and Guatemala have shown that national crisis can easily disrupt these programs leading to recurrence of vitamin A deficiency and its associated diseases. Further attention to achieving adequate diets, reducing frequent infection, and promoting socioeconomic development can help solidify these programs {Underwood, Underwood reference 47}.

The United Nations General Assembly Special Session on Children, held in 2002, was entitled "A World Fit for Children." One section of the draft action plan called for the virtual elimination of vitamin A deficiency diseases by diversifying and fortifying foods, distributing supplements, and recognizing the importance of disease control and poverty reduction. The plan's goal is to eliminate vitamin A deficiency by the year 2010 {Underwood}.

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ANNOTATED PRETEST ANSWERS:

A1. C; Xerophthalmia is a disease of the eye due to vitamin A deficiency. It begins with night blindness and conjunctival xerosis, then progress to corneal xerosis and keratomalacia. Beriberi is an endemic form of polyneuritis due to a deficiency of vitamin B1 (thiamine). Scurvy is a disease caused by a defect in collagen synthesis due to vitamin C deficiency. It is characterized by ulceration of the gums and loss of teeth, hemorrhages into the skin from the mucous membranes and internal organs, and poor wound healing. Pellagra is a disease (pellagra) caused by niacin or tryptophan deficiency and characterized by skin lesions, gastrointestinal disturbances and nervousness. Depression, dermatitis, dementia and diarrhea are common symptoms

A2. B; Both protein and zinc are necessary for the liver production of retinol binding protein (RBP). Vitamin A, after being release from storage in the liver, is shuttled in the serum attached to RBP.

A3. A; This girl has measles - a viral exanthem that may cause complications such as immunosuppression (e.g. otitis media, pneumonia, reactivation of tuberculosis), encephalomyelitis, and subacute sclerosing panencephalitis. C-reactive protein is an acute phase reactant that is released by the liver during periods of infection or systemic inflammation. Retinol binding protein is a negative acute phase reactant. Thus, RBP and retinol will have lower serum levels during the infection. Retinal is a form of vitamin A found in the retina. Supplementation of vitamin A during measles infection has been shown to dramatically decrease morbidity and mortality.

A4. D; A single cup of cantaloupe provides more than 100% of the recommended dietary allowance (RDA) of vitamin A. A cup of whole milk provides 6%, while a cup of skim milk fortified with vitamin A provides 10% of the RDA. A serving of frozen peas provides 10% of the RDA of vitamin A, while a fortified serving of instant oatmeal provides 30%.

A5. A; Retinol is one of the most active, or usable, forms of vitamin A, and is found in animal foods such as liver and eggs and in some fortified food products. Some plant foods contain darkly colored pigments called provitamin A carotenoids that can be converted to vitamin A. Beta-carotene one such carotenoid that is more efficiently converted to vitamin A than other carotenoids, such as alpha-carotene and B-cryptoxanthin. Lycopene is another carotenoid commonly found in food that is not a source of vitamin A, but may have other beneficial effects.