Fatigue / Lassitude, Chronic: definition

What Is Vitamin A?

[dropcap]V itamin A is a family of fat-soluble compounds that are essential for health, vision, protection of the body, reproduction, and normal growth of children before and after birth.

Q: What is the family of vitamin A?

A: The natural vitamin A family members are called retinoids. Retinoids are found only in animal food sources. They include retinol (alcohol form), retinal (aldehyde form), and retinoic acid (acid form).

In the plant kingdom, pigments called carotenoids can yield retinoids on metabolism in the body. Carotenoids that can converted to retinol include β-carotene, α-carotene, and β-cryptoxanthin.¹

There are hundreds of various carotenoids although only a few have been researched including beta-carotene, lycopene, lutein and zeaxanthin.

Fruits and vegetables that are a rich source of carotenoids are thought to provide health benefits by decreasing the risk of various diseases, particularly eye diseases and certain cancers (esophageal, stomach, pancreatic, bladder and cervical). In this respect, research shows that the regular consumption of fruits and vegetables may prevent 20% of most types of cancers.²

In part, the beneficial effects of carotenoids are thought to be due to their role as antioxidants. Lutein and zeaxanthin may be protective in eye disease because they absorb damaging blue light that enters the eye.³

The antioxidant effects appear to be highest in fresh fruit as compared to preserved fruit. A study of fresh peach pulps and peel in animals demonstrated highest antioxidant and anti-inflammatory effects in fresh fruits preventing against induced damage in animal tissues.⁴

A study investigating the specific anti-inflammatory and anti-oxidant micronutrients that reduce oxidative stress showed that adolescents with metabolic syndrome (MetS) had consistently lower carotenoid concentrations compared with their counterparts without MetS. MetS prevalence was estimated at 7% among boys and 3% among girls.⁵

What Is Vitamin A Deficiency In Celiac Disease and/or Gluten Sensitivity?

• Relationship between vitamin A deficiency and celiac disease. Vitamin A deficiency is a classic symptom of celiac disease that results when the level within cells is too low to meet metabolic needs of the body for this vitamin that is caused by malabsorption.
• Relationship between vitamin A deficiency and features. Vitamin A deficiency is characterized by 1) decreased immune function; 2) impaired numbers and responsiveness of T lymphocytes (white blood cells) and increased susceptibility to bacterial, viral, and parasitic infections; 3) impaired vision and eye health; 4) impaired gene regulation which affects growth and development of tissues including bones and the development and maintenance of cells which line the body resulting in poor regeneration of skin and mucous membranes; and 5) impaired reproduction in both males and females for conceiving and producing children.
• Relationship between vitamin A deficiency and  eye health. The macula is a small area in the back of the eye that best receives visual images. Ward et al. found that subjects with malabsorption had 37% lower levels of macular carotenoids on average versus controls. However, malabsorption was not associated with decreased carotenoid levels in blood and convincing signs of early maculopathy were not observed. They suggest that there is a lag between the resolution of blood carotenoid concentrations in patients with malabsorption syndromes (which may resolve within weeks of intestinal recovery) and macular carotenoid concentrations (which may require years to reaccumulate after years of deficiency). If these suppositions are true, they highlight the importance of early detection and monitoring of macular pigment deficiency, and they suggest that extended use of supplements may be required to reduce a patient’s susceptibility to oxidative damage.⁶
• Relationship between vitamin A deficiency and gluten free diet. A study investigating life-long gluten-free diet in celiac disease patients shows that inadequate intake of vitamin A is common (more than 10% of patients) in women and inadequate intake did not relate to nutrient density of the gluten free diet but may relate to habitual poor food choices. “Dietary education should also address the achievement of adequate micronutrient intake.”⁷

How Prevalent Is Vitamin A Deficiency In Celiac Disease and/or Gluten Sensitivity?

Vitamin A deficiency is common in patients with untreated celiac disease.⁸

A Dutch study in 80 newly diagnosed adult patients with celiac disease found the prevalence for vitamin A was 7.5%.⁹

What Does Vitamin A Do In The Body?

1. Essential for production of visual pigments for cells of the retina to see light and dark and color images;
2. Essential for cell differentiation;
3. Essential for cell regulation of bone growth;
4. Essential for proper growth and maintenance of reproductive organs;
5. Helps regulate the immune system, promoting optimal lymphocyte (white blood cell) function in defending against bacterial and viral infections;
6. Promotes healthy skin and mucosal linings of the eyes, respiratory, urinary, reproductive and digestive tracts;
7. Plays a role as an antioxidant.
8. Protects against some cancers.

What Are The Symptoms Of Vitamin A Deficiency?

Vitamin A deficiency is marked by these symptoms:

Eye and Vision Problems:

• Night blindness (cannot see well in low light) and dry eyes  are the earliest eye symptoms.
• Chronic dry eyes (both). Xerosis (dryness) of the bulbar conjunctiva (white of eye) is caused by poor quality and deficient quantity of tears.
• Impaired dark visual adaptation due to inadequate retinal pigment (for example, cannot see well at first when coming inside from daylight or when looking at light objects, the image lingers whether eyes are open or shut.)
• Blurred vision.
• Bitot’s Spots (superficial, irregularly-shaped, white patches on the conjunctiva in both eyes).
• Xerosis (dryness) of the cornea with haziness that can advance to keratomalacia (complete drying of eye surface) then blindness, especially in children with diarrhea.
• Dysfunction of the retina.
• Increased intracranial pressure (pseudocerebri tumor) causing blurred vision which can progress to blindness from deterioration of the optic nerve.

Skin, Hair, and Nails Problems:

• Dry, rough, and scaly skin.
• Hyperkeratosis (plugged hair follicles that look and feel like tiny hard, dry flesh colored bumps, especially on the back of the arms).
• Worsened skin conditons such as psoriasis, eczema, and acne. A nationwide population study found a small excess risk of celiac disease in patients with acne.¹⁰
• Itchy scalp.
• Infections of the skin, hair, and nails.
• Faster aging skin.

Digestive Problems:

• Dry mouth due to low mucous production.
• Low mucous production in the digestive tract.
• Low stomach acid.
• Poor digestion.
• Tongue develops red patches (superficial erosions – loss of mucosa) in marked contrast to unaffected areas of the tongue. Later stages, tongue becomes red and glazed and erosions develop on mucosa of lower inside lip.

Immune Problems:

• Low mucous production in the respiratory, urinary and reproductive tracts all of which predispose to infection.
• Impaired immune function with repeat infections and poor recovery.

Reproductive Problems:

• In males, impaired sperm production may occur.
• In females, spontaneous abortion  may occur.

Childhood Problems:

• In children, growth retardation or abnormal bone formation occurs.
• In children, growth retardation is the most common sign and xerophthalmia leading to keratomalacia is the major cause of blindness. Child mortality can be 50% or more.¹¹

How Does The Body Get Vitamin A?

• The absorption of vitamin A compounds requires their initial digestion. Preformed vitamin A and carotenoids (precursors of vitamin A) from food are released from protein in the stomach.
• The retinol esters are hydrolized (chemically changed) in the small intestine to retinol.
• Retinol levels in blood depend on the presence of amino acids and zinc.¹¹

How Does Vitamin A Deficiency Develop In Celiac Disease and/or Gluten Sensitivity?

• Vitamin A deficiency in celiac disease results from maldigestion and malabsorption from the small intestine due to gluten enteropathy,
• Fat malabsorption because vitamin A is fat soluble and must be absorbed with digested fat.
• As a consequence of disturbed zinc metabolism.¹²
• As a consequence of low stomach acid.

Does Vitamin A Deficiency Respond To Gluten-Free Diet?

Yes. Celiac disease-related Vitamin A deficiency responds to nutritious gluten free diet. Supplementation may be required to correct deficiency.

• Inadequate intake of vitamin A is common (more than 10% of study patients) in women and inadequate intake did not relate to nutrient density of the gluten free diet but may relate to habitual poor food choices. “Dietary education should also address the achievement of adequate micronutrient intake.”¹³

6 Steps To Correct Vitamin A Deficiency:

• [dropcap]1 Meet, or Exceed the RDA (Recommended Dietary Allowances) for Vitamin A in IU per day:

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3000 IU for adult males

2310 IU for adult non-pregnant females.

There are no RDAs for carotenoids.

ADEQUATE ZINC IS REQUIRED for the body to produce retinol binding protein which transports vitamin A in blood. Therefore, a deficiency in zinc limits the body’s ability to mobilize vitamin A stores from the liver.[/box]

• [dropcap]2 Diet – Include Food Sources Richest in Vitamin A:

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Food Sources of Vitamin A ranked by micrograms Retinol Activity Equivalents (RAE) of vitamin A per standard amount; also calories in the standard amount. (All are ≥ 20% of RDA for adult men, which is 900 mg/day RAE.)

Food, Standard Amount	Vitamin A (μg RAE)	Calories
Organ meats (liver, giblets), various, cooked, 3 oza	1490-9126	134-235
Carrot juice, ¾ cup	1692	71
Sweet potato with peel, baked, 1 medium	1096	103
Pumpkin, canned, ½ cup	953	42
Carrots, cooked from fresh, ½ cup	671	27
Spinach, cooked from frozen, ½ cup	573	30
Collards, cooked from frozen, ½ cup	489	31
Kale, cooked from frozen, ½ cup	478	20
Mixed vegetables, canned, ½ cup	474	40
Turnip greens, cooked from frozen, ½ cup	441	24
Instant cooked cereals, fortified, prepared, 1 packet	285-376	75-97
Various ready-to-eat cereals, with added vit. A, ~1 oz	180-376	100-117
Carrot, raw, 1 small	301	20
Beet greens, cooked, ½ cup	276	19
Winter squash, cooked, ½ cup	268	38
Dandelion greens, cooked, ½ cup	260	18
Cantaloupe, raw, ¼ medium melon	233	46
Mustard greens, cooked, ½ cup	221	11
Pickled herring, 3 oz	219	222
Red sweet pepper, cooked, ½ cup	186	19
Chinese cabbage, cooked, ½ cup	180	10

^a High in cholesterol.

Source: Nutrient values from Agricultural Research Service (ARS) Nutrient Database for Standard Reference, Release 17. Foods are from ARS single nutrient reports, sorted in descending order by nutrient content in terms of common household measures. [/box]

• [dropcap]3  Diet – Avoid, Limit, or Eat Separately These Foods That Deplete or Interfere With Absorption:

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• Refined cooking oil (bad) of any type such as olive oil, canola oil, corn oil, safflower oil, sunflower oil, or cottonseed oil. Refining is a misleading term that means a production process for chemically obtaining residual oil from seeds that have been pressed out. Pressed oils (good) would say “virgin olive oil” or “cold-pressed canola oil” for example.
• Refined sugar including white sugar, confectioner’s sugar, corn syrup, and fructose.
• Excessive alcoholic drinks.
• Olestra (a fat substitute found in snacks foods like potato chips) inhibits absorption of vitamin A.

[/box][dropcap]4 Monitor Medications That Deplete or Interfere With Absorption:

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Here are common medications that deplete vitamin A. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

This is not a complete listing.

• Cholesterol drugs – fat binding medications like Colestid®, Questran®.
• Bile acid sequestrants like cholestyramine, colestipol.
• Antacids/Ulcer Medications – Pepcid®, Tagamet®, Zantac®.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®).[/box]

• [dropcap]5 Manage Nutritional Supplements to Obtain Vitamin A:

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• A blood level concentration should be obtained to determine status before supplementing and which provides a baseline if supplementation with vitamin A is needed.
• Natural preparations provide the best benefit over synthetic ones that are chemically produced.
• Avoid preparations that say “retinyl acetate” because these employ the use of benzene which is a highly toxic chemical that is proved to cause blood disorders and cancers.
• Vitamin A dry tablets do not contain oils and therefore should be taken with food containing fat.
• Vitamin A gel capsules usually contain oil which acts to help absorption. However, avoid this type if you are allergic to the oil such as soybean oil.
• Fish oil preparations that contain vitamin A are a rich source.
• Beta-carotene preparations should only be used if they are derived from food sources otherwise it is best to eat the foods themselves for maximum benefit.
• Avoid synthetic preparations of bete-carotene such as Lurotin® because it is made from the deadly chemical called benzene and therefore toxic and anti-nutritional…this is the particular preparation used in the research study, Physicians’ Health Study II (PHS II), that caused increased lung cancer in participants. This study was designed in part to test the effectiveness of beta-carotene in preventing cancer but succeeded in showing the dangers of synthetic beta-carotene instead.
• Avoid any preparation that contains these harmful chemicals most of which are derived from benzene a toxic hydrocarbon, C6H6): benzoic acid, methyparaben (found in breast cancer tissue taken from patients, in eye drops it damages the eye surface), propylparaben, paraben, polyethylene glycol, propylene glycol (propanediol), polysorbate 60.

CAUTION: EXCESSIVE VITAMIN A INTAKE BY SUPPLEMENTATION ESPECIALLY THE DRY TABLET FORM IS TOXIC AND MUST BE AVOIDED.

• Prevent children access to vitamin A supplements.
• Liver abnormalities, reduced bone density and central nervous system disorders may result from overdose.
• Early toxicity signs include bleeding from gums, confusion or unusual excitement, drowsiness, peeling/ itching skin, especially on palms and lips, and brittle nails.
• Prolonged overuse may result in hair loss, bone/joint pain, yellowish skin and unusual fatigue.
• Vitamin A toxicity causes increased intracranial pressure (hypertension).
• Natural (not synthetic) beta-carotene and mixed carotenoids are much less toxic and not associated with the commonly noted side effects of excess vitamin A intake.

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• [dropcap]6 Supplements That Deplete or Interfere With Absorption:

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• The iron supplements ferrous sulfate and ferric chloride (not ferrous fumarate or ferrous gluconate) can damage vitamin A. Check with your pharmacist.[/box]

Medical Research Findings On Vitamin A Deficiency In Celiac Disease and/or Gluten Sensitivity:

RESEARCH STUDY SUMMARIES

“Pediatric Pseudotumor Cerebri Associated With Low Serum Levels of Vitamin A.” The aim of this study was to describe the association between pediatric pseudotumor cerebri and low serum vitamin A levels. Researchers retrospectively reviewed the charts of 6 children (5 boys, 1 girl; mean age 8 years) with increased intracranial pressure and low serum vitamin A levels (mean 16.0 ± 8.8 µg/dL). The etiology of the vitamin A deficiency was a restricted diet (2 children), intestinal malabsorption caused by celiac disease (2 children), and undetermined cause (2 children). Only 1 child had ocular signs of xerosis. Poor visual acuity at presentation and lower serum vitamin A levels were associated with a poor visual outcome and development of optic atrophy.

In conclusion, pseudotumor cerebri in children can be associated withvitamin A deficiency even when other manifestations of xerophthalmia do not exist. Early recognition of this condition and appropriate therapy can prevent blindness.¹⁴

“Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients.” This study aiming to assess the nutritional and vitamin/mineral status of current “early diagnosed” untreated adult celiac disease (CD)-patients in the Netherlands found that vitamin/mineral deficiencies are still common in newly “early diagnosed” CD-patients, even though the prevalence of obesity at initial diagnosis is rising. Eighty newly diagnosed adult CD-patients were included and a comparable sample of 24 healthy Dutch subjects was added to compare vitamin concentrations.

Nutritional status and serum concentrations of folic acid, vitamin A, vitamin B6, vitamin B12, and (25-hydroxy) vitamin D, zinc, haemoglobin (Hb) and ferritin were determined (before prescribing gluten free diet). Almost all CD-patients (87%) had at least one value below the lower limit of reference. Specifically, for vitamin A the prevalence was 7.5% of patients showed deficient levels.

Vitamin/mineral deficiencies were counter-intuitively not associated with a (higher) grade of histological intestinal damage or (impaired) nutritional status. Extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in CD treatment.⁹

“Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with celiac disease.” This study investigating life-long gluten-free diet (GFD) in celiac disease patients aimed to determine the nutritional adequacy of the ‘no detectable gluten’ diet. Results show that inadequate intake of vitamin A is common (more than 10%) in women and may relate to habitual poor food choices in addition to inherent deficiencies in the GFD. “Dietary education should also address the achievement of adequate micronutrient intake.”

A seven-day prospective food intake was assessed in 55 patients who were adherent to a GFD for more than 2 years and in 50 newly-diagnosed age- and sex-matched patients (18-71 years, 24% male) studied prospectively over 12 months on GFD. Historical pre-celiac intake was also assessed in the latter group. Intake was compared with Australian Nutritional Recommendations and the Australian population data.

RESULTS: Nutritional intake was similar between groups. Of macronutrients, only starch intake fell over 12 months (26% to 23%). Fibre intake was inadequate for all except in diet-experienced men. More than one in 10 of both newly-diagnosed and experienced women had inadequate thiamin, folate, vitamin A, magnesium, calcium and iron intakes. More than one in 10 newly-diagnosed men had inadequate thiamin, folate, magnesium, calcium and zinc intakes. Inadequate intake did not relate to nutrient density of the GFD. Inadequacies of folate, calcium, iron and zinc occurred more frequently than in the Australian population. The frequency of inadequacies was similar pre- and post-diagnosis, except for thiamin and vitamin A, where inadequacies were more common after GFD implementation.  Because dietary intake patterns at 12 months on a GFD are similar to longer-term intake, researchers stress that fortification of GF foods also need to be considered.”⁷

“Serum antioxidant concentrations and metabolic syndrome are associated among U.S. adolescents in recent national surveys.” This study investigated whether specific anti-inflammatory and anti-oxidant micronutrients that reduce oxidative stress are associated with the occurrence of metabolic syndrome (MetS), HOMA-IR (insulin resistance index), and C-reactive protein, and hyperuricemia (elevated serum uric acid) in the adolescent U.S. population.

Findings show that serum carotenoid concentrations were inversely associated (opposite) with MetS status, HOMA-IR (insulin resistance index), and C-reactive protein. Retinol+retinyl esters (vitamin A) had a positive relationship with HOMA-IR, uric acid, and MetS, while being inversely related to C-reactive protein.

MetS was defined by the International Diabetes Federation criteria. Other non-MetS outcomes relying on blood measurements were elevated HOMA-IR, C-reactive protein (CRP), and hyperuricemia. Associations between serum antioxidants and MetS outcomes were tested among adolescents aged 12-19 y using cross-sectional data from NHANES 2001-2006 (n = 782-4285). MetS prevalence was estimated at 7% among boys and 3% among girls. In adjusted models, adolescents with MetS had consistently lower carotenoid concentrations compared with their counterparts without MetS.⁵

“Macular and serum carotenoid concentrations in patients with malabsorption syndromes.” This controlled cross-sectional study investigating whether subjects with nutrient malabsorption syndromes have lower carotenoid levels in the macula and blood and the correlation with early-onset maculopathy due to macular pigment deficiency demonstrated that 22 subjects with malabsorption had 37% lower levels of macular carotenoids on average versus 25 controls. Malabsorption was not associated with decreased carotenoid levels in blood and convincing signs of early maculopathy were not observed.

Subjects included 18 with celiac disease and 4 with Crohn’s disease who were younger than 55 years of age with good ocular function in the tested eyes. Resonance Raman spectrographic (RRS) measurements of macular carotenoid levels were collected from subjects with and without a history of malabsorption syndromes. Carotenoids were extracted from serum and analyzed by high performance liquid chromatography (HPLC).  “Despite the fact that this study did not demonstrate convincing maculopathy at the time of examination, these patients certainly could be at risk for ongoing long-term macular oxidative stress that could predispose to age-related macular degeneration later in life. We conclude that intestinal malabsorption results in lower macular carotenoid levels. ”¹⁵

CASE REPORT SUMMARIES

“Bitot’s Spots: Look at the Gut.” This case report describes finding celiac disease manifested by Bitot’s spots due to vitamin A deficiency in a 10-year-old boy who presented with diarrhea since 1 year. He used to pass multiple stools in a day. He also complained of decreased vision in low lighting. The child was malnourished, had pallor and height for age and weight for age were lower than the 3rd percentile. He was eldest of the three siblings and belonged to a poor rural family.

He also had superficial, irregularly-shaped, white lesions on the conjunctiva in both eyes. Mild pitting pedal edema was noted and systemic examination was normal. Evaluation revealed low hemoglobin of 8 mg/dL (Normal 12-16 mg/dL), microcytes in peripheral smear and a mean corpuscular volume of 71 mm3, normal leukocyte count and thrombocytosis (5 lakh/mm3). The patient had low serum albumin (2.8 g/dL, Norma: 3.5-5 g/dL) and mild transaminitis (Alanine transaminase – 71 U/L, Normal: 0-35 U/L, aspartate transaminases AST- 75 U/L, 7-41 U/L) with a normal level of bilirubin. The work-up for cause of transaminitis (low liver enzymes) including viral markers (surface antigen for hepatitis B and antibodies to hepatitis C virus) were nonreactive. Upper gastoduodenoscopy showed grooving and scalloping in second part of duodenum. Duodenal biopsy revealed subtotal villous atrophy. immunoglobulin A (IgA) tissue transglutaminase was 213 U/mL (Normal: 0-8 U/mL).¹⁶

“Vitamin A deficiency in coeliac disease.” This case report describes an ophthalmological diagnosis of vitamin A deficiency secondary to celiac disease.  A 64 year old man presented to his eye doctor with a six week history of sudden progressive redness of his right eye associated with blurring of vision. His left eye was asymptomatic and he had no ocular history of note. He had a history of diet controlled celiac disease proved by jejunal biopsy. Several weeks earlier he had complained of persistent diarrhea despite adherence to his gluten-free diet. On examination the right eye was diffusely injected and the cornea showed filamentary changes with multiple underlying punctate epithelial staining defects. There were no other pathological defects.

A provisional diagnosis of filamentary keratitis was made and he was treated with topical acetylcysteine to the right eye and topical lubricants to the left eye. Two weeks later he reported marked deterioration in symptoms. Visual acuity remained unchanged.  Corneal examination revealed a large central full thickness epithelial defect. Regular topical lubricants were applied and a botulinum toxin injection  was administered. After one week there was a complete failure of re-epithelialization. The suspicion of keratomalacia secondary to vitamin A deficiency was raised and an intramuscular injection of 100,000 units of vitamin A was administered. Subsequent serum vitamin A level was 13 (normal 330 – 1100). Six days later there was dramatic symptomatic improvement. The cornea was almost completely healed with only a few area of corneal deficits remaining. The patient was referred back to the gastroenterologists who investigated his continuing malabsorption. One month later, ocular examination revealed complete healing of the right eye. Vitamin A is obtained from the diet and is required in the cornea for maintaining epithelial (surface cell) integrity.¹⁷

Sources:

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4. Gasparotto J, Somensi N, Bortolin RC, Moresco KS, Girardi CS, Klafke K, Rabelo TK, Morrone Mda S, Vizzotto M, Raseira Mdo C, Moreira JC, Gelain DP. Effects of different products of peach (Prunus persica L. Batsch) from a variety developed in southern Brazil on oxidative stress and inflammatory parameters in vitro and ex vivo. J Clin Biochem Nutr. 2014 Sep;55(2):110-9. doi: 10.3164/jcbn.13-97. [↩]
5. TGBeydoun MA, Canas JA, Beydoun HA, Chen X, Shroff MR, Zonderman AB. Serum antioxidant concentrations and metabolic syndrome are associated among U.S. adolescents in recent national surveys. J Nutr. 2012 Sep;142(9):1693-704. doi: 10.3945/jn.112.160416. [↩] [↩]
6. Ward MS, Zhao da Y, Bernstein PS. Macular and serum carotenoid concentrations in patients with malabsorption syndromes. J Ocul Biol Dis Infor. 2008 Mar;1(1):12-8. doi: 10.1007/s12177-008-9008-0. [↩]
7. Shepherd SJ1, Gibson PR. Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with coeliac disease. J Hum Nutr Diet. 2013 Aug;26(4):349-58. doi: 10.1111/jhn.12018. [↩] [↩]
8. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
9. Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJ, van Bodegraven AA. Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients. Nutrients. 2013 Sep 30;5(10):3975-92. doi: 10.3390/nu5103975. [↩] [↩]
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12. Scholmerich J, Wietholtz H, Buchsel R, Kottgen E, Lohle E, Gerok W. Zinc and vitamin A deficiency in gastrointestinal diseases. Leber, Magen, Darm. Nov 1984; 14(6):625-36. [↩]
13. Shepherd SJ1, Gibson PR. Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with coeliac disease. J Hum Nutr Diet. 2013 Aug;26(4):349-58. doi: 10.1111/jhn.12018.)
14. If early detection of macular pigment deficiency is found, extended use of supplements may be required to reduce a patient’s susceptibility to oxidative damage to the macula of the eye. ((Ward MS, Zhao da Y, Bernstein PS. Macular and serum carotenoid concentrations in patients with malabsorption syndromes. J Ocul Biol Dis Infor. 2008 Mar;1(1):12-8. doi: 10.1007/s12177-008-9008-0. [↩]
15. Dotan G, Goldstein M, Stolovitch C, Kesler A. Pediatric pseudotumor cerebri associated with low serum levels of Vitamin A. J Child Neurol. 2013 Nov;28(11):1370-1377. [↩]
16. Ward MS, Zhao da Y, Bernstein PS. Macular and serum carotenoid concentrations in patients with malabsorption syndromes. J Ocul Biol Dis Infor. 2008 Mar;1(1):12-8. doi: 10.1007/s12177-008-9008-0. [↩]
17. Sharma A, Aggarwal S, Sharma V. Bitot’s Spots: Look at the Gut. Int J Prev Med. 2014 Aug;5(8):1058-9. [↩]
18. Alwitry A. Vitamin A deficiency in coeliac disease. Br J Ophthalmol. 2000 September; 84(9): 1075. doi:  10.1136/bjo.84.9.1075e [↩]