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What Is Vitamin C?

[dropcap]V itamin C, also called ascorbic acid or ascorbate, is an essential water soluble vitamin.

Fresh supplies of vitamin C are required every day to perform vital roles throughout the body among which are the production of connective tissue such as skin, blood vessels and bone, anti-inflammatory responses and anti-oxidant performance. See below for all roles.

Vitamin C fights for us! It has an anti-cancer effect stemming from its role as a potent anti-oxidant in blood plasma and within cells. It also protects nucleic acids (DNA) from oxidative damage and inhibits the formation of nitrosamines (carcinogenic compounds formed in the digestive tract).

Importantly, vitamin C can regenerate vitamin E from an oxidized state after vitamin E performs its own anti-oxidant role against free radicals and vitamin C works together with other anti-oxidants, such as beta-carotene and glutathione, to increase their overall anti-oxidant effect.

A study investigating the specific anti-inflammatory and anti-oxidant micronutrients that reduce oxidative stress found that in adolescents with metabolic syndrome (MetS) the lower the vitamin C level in blood the worse the MetS status and blood uric acid level.  MetS prevalence was estimated at 7% among boys and 3% among girls.¹

Vitamin C reverses osteoporosis by reducing or preventing oxidative stress that destroys living bone tissue. Osteoporosis is a disorder of bone inflammation that results in thin, weak bones that may easily fracture. In normal bone structure, vitamin C is required to form collagen, which is living bone tissue.

In humans, vitamin C reduces the duration of common cold symptoms, even if its effect is not clear.²

Vitamin C must be obtained from food daily because our bodies, unlike monkeys and other animals, cannot produce it.

Urinary excretion of vitamin C cannot be detected when vitamin intake is below the required levels. On the other hand, when intake exceeds saturation in the body, the vitamin and/or its metabolites are actively excreted into urine to prevent excessive toxicity of the vitamins.³

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

• Relationship between vitamin C deficiency and gluten sensitivity (celiac disease, non-celiac disease, allergy to gluten). Vitamin C deficiency results when the level within cells is too low to meet needs of the body for this vitamin caused by malabsorption in celiac disease and the depleting effects of inflammation in gluten sensitivity including celiac disease, non-celiac gluten sensitivity and allergy.

• Relationship between vitamin C deficiency and features. Vitamin C deficiency is characterized by impairment in its metabolic functions as an enzyme cofactor, an anti-oxidant protector against free radicals, and a reactant with metals, crucial in detoxification. Each of these functions involves the oxygen reduction/oxidation properties of the vitamin, called “redox.”

• Relationship between vitamin C deficiency and scurvy. Untreated vitamin C deficiency can progress in about 45 to 80 days to the disease called scurvy that if left untreated advances to death.

• Relationship between vitamin C and intestinal inflammation caused by gluten. Vitamin C has been shown to down regulate (reduce) the mucosal inflammatory response to gluten in an intestinal biopsy culture model.⁴

• Relationship between vitamin C deficiency and inflammation in gluten sensitivity (celiac disease, non-celiac disease, allergy to gluten).  Vitamin C, with or without malabsorption, is depleted or used up by its activity in reducing inflammation in gluten sensitivity and any other condition that involves inflammation such as osteoporosis.

• Relationship between vitamin C deficiency and histamine. Vitamin C depletion has been correlated with histaminemia (elevated histamine in blood) which has been shown to damage endothelial-dependent vasodilation.⁵ Endothelial-dependent vasodilation is the ability of blood vessel walls of arteries to dilate or relax when required. Inability of arteries carrying blood away from the heart causes elevated blood pressure.

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

Vitamin C deficiency is common in patients with untreated celiac disease.⁶

What Are The Symptoms Of Vitamin C Deficiency?

Vitamin C deficiency is marked by these symptoms in alphabet order:

• Anemia (due to vitamin C’s ability to enhance iron absorption).
• Bone weakening and thinning (osteopenia) that can advance to osteoporosis due to reduction in anti-inflammation capability.
• Capillary fragility (due to its role in collagen formation) shows as bleeding gums, easy bruising, petechiae, and splinter hemorrhages in nails.
• Coiling of hair in the skin, especially where there is friction such as the hips, buttocks, and thighs.
• Depression.
• Edema of the lower extremities appears late.
• Eye floaters/ eye flashes due to poor collagen within the eye.
• Fatigue (due to its role in the production of carnitine and certain hormones).
• Gingivitis – swollen gums appear red in children and purplish in adults.
• Hypochondria.
• Hysteria.
• Immunity, lowered.
• In infants, weakness of bone, teeth, cartilage, and connective tissue, edema, and hemorrhages (due to gluten in formula) occur.
• Inflammatory conditions worsen.
• Irritability.
• Joint pain. Joints become tender (arthritis resembling rheumatoid arthritis).
• Lethargy.
• Muscle loss (muscle wasting).
• Muscle spasm/cramps.
• Muscle weakness.
• Periodontal disease with eventual tooth loss from infection.
• Poor wound healing.
• Refusal to walk in young children due to pain.
• Rheumatic pains in legs.
• Tooth decay.

Subclinical deficiency (low level) can also result in lowered immunity, anemia and fatigue.

How Does The Body Get Vitamin C?

Vitamin C is absorbed by active transport as well as passive diffusion from the small intestine. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms.⁷

What Does Vitamin C Do In The Body?

Vitamin C is essential for these functions in the body:

1. Growth and repair of all tissues in the body.
2. Production of collagen (tendons, ligaments) and elastin (the main structural proteins of skin, cartilage and blood vessels).
3. Absorption of iron from the small intestine.
4. Promoting efficient wound healing;
5. Detoxifying the body by binding to certain heavy metals so they can be eliminated from the body.
6. Boosting immunity by increasing production of white blood cells, increasing levels of antibodies and interferon and regulating prostaglandin production.
7. Production of several stress response hormones including adrenalin, noradrenalin, cortisol and histamine.
8. Production of carnitine, an amino acid, that facilitates the conversion of fatty acids into energy.
9. Involved in the transfer of iron from plasma transferrin to liver ferritin.
10. Co-substrate for at least 8 enzymes, of which it is best characterized in the role of the hydroxilation of proline to form hydroxyproline in the synthesis of collagen tissue.
11. Protection against heart disease by helping to dissolve arterial plaque, reducing free radical oxidation of cholesterol, decreasing levels of harmful cholesterol, and maintaining the elasticity of blood vessel walls which helps control hypertension.
12.  Ascorbic acid  is an important anti-oxidant in the eye.⁸

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

• Vitamin C deficiency in celiac disease results from malabsorption.
• Physical or emotional stress that develops from other malabsorptions deplete vitamin C.
• Inflammation caused by gluten depletes vitamin C.

Does Vitamin C Deficiency Respond To Gluten-Free Diet?

Yes. Celiac disease-related vitamin C deficiency responds quickly to gluten free diet containing adequate vitamin C.

6 Steps To Correct Vitamin C Deficiency:

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

[box type=”success” ] 40 mg for infants birth-6 months;50 mg for infants 7-12 months;

15 mg for children 1-3 years; 25 mg for children 4-8 years;

45 mg for children 9-13 years;

75 mg for male teens 14-18 years; 65 mg for female teens 14-18 years;

90 mg for males 19 years and older; 75 mg for females 19 years and older;

80 mg for pregnancy; 115 mg for breastfeeding women.[/box]

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

[box type=”shadow” ] Plant Sources:

Food Sources of Vitamin C ranked by milligrams of vitamin C per standard amount; also calories in the standard amount. (All provide ≥ 20% of RDA for adult men, which is 90 mg/day.)

Food, Standard Amount	Vitamin C (mg)	Calories
Guava, raw, ½ cup	188	56
Red sweet pepper, raw, ½cup	142	20
Red sweet pepper, cooked, ½ cup	116	19
Kiwi fruit, 1 medium	70	46
Orange, raw, 1 medium	70	62
Orange juice, ¾ cup	61-93	79-84
Green pepper, sweet, raw, ½ cup	60	15
Green pepper, sweet, cooked, ½ cup	51	19
Grapefruit juice, ¾ cup	50-70	71-86
Vegetable juice cocktail, ¾ cup	50	34
Strawberries, raw, ½ cup	49	27
Brussels sprouts, cooked, ½ cup	48	28
Cantaloupe, ¼ medium	47	51
Papaya, raw, ¼ medium	47	30
Kohlrabi, cooked, ½ cup	45	24
Broccoli, raw, ½ cup	39	15
Edible pod peas, cooked, ½ cup	38	34
Broccoli, cooked, ½ cup	37	26
Sweet potato, canned, ½ cup	34	116
Tomato juice, ¾ cup	33	31
Cauliflower, cooked, ½ cup	28	17
Pineapple, raw, ½ cup	28	37
Kale, cooked, ½ cup	27	18
Mango, ½ cup	23	54

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.

Animal Sources: do not contain vitamin C.

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

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• Alcohol consumption.
• Refined sugars.
• Foods produced with nitrates and nitrites such as cold cuts, sausage, and hotdogs.

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

Certain prescription drugs can cause deficiency. Ask your doctor or pharmacist about possible interactions between vitamin C supplements and medications you’re taking to make sure you time the doses correctly. DO NOT STOP PRESCRIPTION MEDICATIONS WITHOUT CONSULTING YOUR PHYSICIAN.

[box type=”shadow” ]Here are common medications that increase risk and should to be monitored for deficiency:

Below is not a complete listing.

ANTIBIOTICS

• (Gentomycin, Neomycin, Streptomycin, Cephalosporins, Penicillins).

ANTI-INFLAMMATORIES

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron).
• Aspirin and Salicylates.

LOOP DIURETICS

• (Lasix®, Bumex®, Edecrin®).

FEMALE HORMONES

• Oral Contraceptives (Norinyl®, Ortho-Novum®, Triphasil®, and others).
• Oral Estrogen/Hormone Replacement (Evista®, Prempro®, Premarin®, Estratab® and others).[/box]

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

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Supplementation of vitamin C improves the function of the human immune system, such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis and delayed-type hypersensitivity.⁵

• Ascorbic acid is available without prescription in tablet form, extended-release capsules, lozenges, syrup, chewable tablets, and liquid drops, and as part of multivitamin supplements.
• Large doses should be spaced throughout the day for best effect since the body readily excretes excess vitamin C shortly after ingestion. Large doses may result in diarrhea.
• Mineral ascorbates are the preferred supplement form (versus ascorbic acid) to maximize absorption. The safest ascorbic acid combinations are with sodium or magnesium.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet  – not in the bathroom or on the kitchen table.

Caution: Excess vitamin C can have an opposite effect of increasing free radical production, therefore it is important to balance it with other antioxidants. The Tolerable Upper Intake Level has been established at 2,000 mg per day.[/box] 

• [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 C. Check with your pharmacist.[/box]

What Do Medical Research Studies Tell About Vitamin C Deficiency In Celiac Disease and/or Gluten Sensitivity:

RESEARCH STUDY SUMMARIES

“Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in celiac disease patients.“ This study investigating if  ascorbate (vitamin C) supplementation to gliadin-stimulated biopsy culture could down-regulate the mucosal immune response to gliadin in celiac disease found that ascorbate does decrease the mucosal inflammatory response to gluten in an intestinal biopsy culture model.

Duodenal biopsy explants from treated celiac disease patients were gliadin challenged in vitro (100 μg/ml) with and without 20mM vitamin C. An extra tissue explant in basal culture was used as internal control.

The addition of ascorbate to in vitro culture gliadin-challenged biopsies blocked the secretion of the pro-inflammatory cytokines nitrites, IFNγ, TNFα, IFNα, and IL-6 compared to samples from non-ascorbate supplemented culture. Cytokine secretion was downregulated by ascorbate even to lower values than those observed in basal cultures.

Gliadin-challenge induced IL-15 (interleuken-15) production in biopsies from treated celiac disease patients, while the addition of ascorbate to culture medium completely inhibited IL-15 production. Moreover, the inhibition of IL-15 by ascorbate took place even in the only treated celiac disease-patient who had basal IL-15 production.⁹

“Intestinal absorption of water-soluble vitamins in health and disease.“ Humans cannot synthesize water-soluble vitamins (with the exception of some synthesis of niacin) and must obtain these micronutrients from dietary sources. Thus body homoeostasis (balance) of these micronutrients depends on their normal absorption in the intestine. Interference with absorption leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities.

It is well established now that intestinal absorption of the water-soluble vitamin ascorbate (vitamin C) is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms.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 vitamin C was inversely related to MetS status and serum uric acid.

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.¹⁰

CASE REPORT SUMMARIES

“Scurvy revealed by difficulty walking: three cases in young children.” This case report describes 3 cases of scurvy in young children presenting with difficulty walking. Only 1 of 3 patients had gingival lesions at the initial presentation. Two cases underwent an extensive evaluation for hematologic and rheumatologic diseases before the diagnosis of scurvy was made. Dietary histories eventually revealed that all 3 patients had sharply limited intake of fruits and vegetables secondary to oral aversion, and 1 patient had autism.

Radiographic changes of long bones were observed in all patients. Interestingly, all patients had concomitant vitamin D deficiency. After replacement with vitamin C, all patients recovered and started to walk again with improved leg pain. These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children.¹¹

“Eat a citrus fruit, stay healthy–a case report of scurvy.” This case report describes finding scruvy in a 7-year-old patient with a medical history of hydrocephalus, failure to thrive and severe psychomotor retardation due to complications of prematurity. On admission she had gum bleeding, severe anemia, pain in the lower limbs and refused to stand and walk. According to her parents, her diet was restricted, without vegetables or fruit consumption. Our investigation ruled out coagulopathy, malignancy and infection. Serum vitamin C levels were low and radiographic findings were consistent with the diagnosis of scurvy. The patient improved rapidly after the initiation of vitamin C supplements. Despite being rare, scurvy should be considered in the differential diagnosis of bleeding and pain in the lower limbs, especially in a malnourished patient.¹²

“Celiac disease manifested by polyneuropathy and swollen ankles.” This is a case study revealing celiac disease in a 27-year-old male who started to have his ankles swollen during his military service. He was examined at a military hospital where electromyoneurography showed the signs of distal sensory-motor polyneuropathy with axon demyelinization and weak myopathic changes, whereas histopathological examination of gastrocnemius muscle biopsy revealed some mild and nonspecific myopathy. Besides, he was found to have subcutaneous ankle tissue edemas and hypertransaminasemia. Due to these reasons, he was dismissed from the military service and examined at another hospital where bone osteodensitometry revealed low bone mineral density of the spine.

However, his medical problems were not resolved and after the second discharge from hospital he was desperately seeing doctors from time to time. Finally, at our institution he was shown to have celiac disease by positive serology (antitissue transglutaminase and antiendomysial antibodies) and small bowel mucosal histopathological examination, which showed total small bowel villous atrophy. Three months after the initiation of gluten-free diet, his ankle edema disappeared, electromyoneurographic signs of polyneuropathy improved and liver aminotransferases normalized. Good knowledge of celiac disease extraintestinal signs and serologic screening are essential for early celiac disease recognition and therapy.¹³

“An orange a day keeps the doctor away: scurvy in the year 2000.” This case report describes finding scurvy in a 9-year-old developmentally delayed girl who had a diet markedly deficient in vitamin C resulting from extremely limited food preferences. She presented with debilitating bone pain, inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe hypertension without another apparent secondary cause was also present, which has been previously undescribed. The signs of scurvy and hypertension resolved after treatment with vitamin C. The diagnosis of scurvy is made on clinical and radiographic grounds, and may be supported by finding reduced levels of vitamin C in serum or buffy-coat leukocytes. The response to vitamin C is dramatic. Clinicians should be aware of this potentially fatal but easily curable condition that is still occasionally encountered among children.¹⁴

Sources:

1. 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. [↩]
2. Shaik-Dasthagirisaheb YB, Varvara G, Murmura G, Saggini A, Caraffa A, Antinolfi P, Tete’ S, Tripodi D, Conti F, Cianchetti E, Toniato E, Rosati M, Speranza L,Pantalone A, Saggini R, Tei M, Speziali A, Conti P, Theoharides TC, Pandolfi F. Role of vitamins D, E and C in immunity and inflammation. J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2):291-5. [↩]
3. Shibata K, Hirose J, Fukuwatari T. Relationship Between Urinary Concentrations of Nine Water-soluble Vitamins and their Vitamin Intakes in Japanese Adult Males. Nutr Metab Insights. 2014 Aug 5;7:61-75. doi: 10.4137/NMI.S17245. eCollection 2014. [↩]
4. Bernardo D, Martínez-Abad B, Vallejo-Diez S, Montalvillo E, Benito V, Anta B, Fernández-Salazar L, Blanco-Quirós A, Garrote JA, Arranz E. Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in celiac disease patients. Allergol Immunopathol (Madr). 2012 Jan-Feb;40(1):3-8. doi: 10.1016/j.aller.2010.11.003. [↩]
5. Shaik-Dasthagirisaheb YB, Varvara G, Murmura G, Saggini A, Caraffa A, Antinolfi P, Tete’ S, Tripodi D, Conti F, Cianchetti E, Toniato E, Rosati M, Speranza L,Pantalone A, Saggini R, Tei M, Speziali A, Conti P, Theoharides TC, Pandolfi F. Role of vitamins D, E and C in immunity and inflammation. J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2):291-5. [↩] [↩]
6. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
7. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011 Aug 1;437(3):357-72. doi: 10.1042/BJ20110326. [↩] [↩]
8. Ma N, Siegfried C, Kubota M, Huang J, Liu Y, Liu M, Dana B, Huang A, Beebe D, Yan H, Shui YB. Expression Profiling of Ascorbic Acid-Related Transporters in Human and Mouse Eyes. Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3440-50. doi: 10.1167/iovs.16-19162. [↩]
9. Bernardo D, Martínez-Abad B, Vallejo-Diez S, Montalvillo E, Benito V, Anta B, Fernández-Salazar L, Blanco-Quirós A, Garrote JA, Arranz E. Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in coeliac disease patients. Allergol Immunopathol (Madr). 2012 Jan-Feb;40(1):3-8. doi: 10.1016/j.aller.2010.11.003. [↩]
10. 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. [↩]
11. Kitcharoensakkul M, Schulz CG, Kassel R, Khanna G, Liang S, Ngwube A, Baszis KW, Hunstad DA, White AJ. Scurvy revealed by difficulty walking: three cases in young children. J Clin Rheumatol. 2014 Jun;20(4):224-8. doi: 10.1097/RHU.0000000000000101. [↩]
12. Ben-Shimol S, Greenberg D. Eat a citrus fruit, stay healthy–a case report of scurvy. Harefuah. 2012 Jun;151(6):327-9, 380. [↩]
13. Djuric Z, Kamenov B, Katic V. Celiac disease manifested by polyneuropathy and swollen ankles. World J Gastroenterol. 2007 May 14;13(18):2636-8. [↩]
14. Weinstein M, Babyn P, Zlotkin S. An orange a day keeps the doctor away: scurvy in the year 2000. Pediatrics. 2001 Sep;108(3):E55. [↩]