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Introduction: Scurvy, or "Barlow's disease", is a widely described disease involving cutaneous and mucosal lesions resulting from vitamin C deficiency. Herein, we report a case of scurvy in a 48-year-old woman that was unusual in its atypical cutaneous-mucosal presentation as well as its association with anorexia nervosa., Patients and Methods: A 48-year-old woman treated for depression for several years was admitted to hospital for her impaired general state of health. Over the last year, she had presented palmoplantar rash and episodes of perimalleolar oedema. The clinical examination showed the patient to have wasting syndrome, with a BMI of 11.9kg/m 2 , lower-limb oedema, palmoplantar fissures, geographic tongue, telogen effluvium and purpuric petechiae on her right knee. However, no gingival bleeding was noted and there was no loss of tooth enamel. The remainder of the clinical examination was normal. Blood tests revealed extremely low vitamin C levels without any other associated deficiencies, as well as laboratory signs of cytolysis and anicteric cholestasis without inflammatory syndrome. The diagnosis of anorexia nervosa was made by psychiatrists, despite the unusual age of onset. Favorable clinical outcome was rapidly achieved via a one-month course of vitamin C supplements at a daily dose of 1g., Discussion: The absence of classical buccal-dental symptoms and the presence of keratotic dermatosis with fissures and ulcers on the hands and feet are atypical in scurvy; however, this diagnosis was confirmed by the existence of purpura evoking capillary fragility, the patient's drastically low vitamin C level and the rapid subsidence of symptoms following treatment with oral vitamin C alone. Anorexia nervosa was doubtless the cause of deficiency. This situation is rare and a systematic review of the literature in Medline via PubMed showed that only three reports of scurvy associated with mental anorexia have been published since 1975., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Importance: Scurvy remains prevalent in certain populations, including addicts, people of low socioeconomic status, and the severely malnourished. It classically presents as follicular hyperkeratosis and perifollicular hemorrhage of the lower extremities, as well as bleeding in other areas such as the gingiva and joints. This case presentation and literature review highlights the common pathophysiological findings associated with scurvy and current methods of diagnosis and treatment., Observation: The patient described in this case presented with sudden oligoarthritis and purpura of the lower extremities. Following progression of the patient's symptoms and a low vitamin C serum concentration, the patient was treated with vitamin C supplementation and dramatically improved. This was considered to be the result of an underlying vitamin C deficiency secondary to insufficient fruit and vegetable intake due to allergies., Conclusions and Relevance: This case highlights the importance of maintaining a high index of suspicion for scurvy in atypical presentations of purpura not better explained by another disease or in additional populations at high risk of vitamin C deficiency. Early diagnosis by either a primary care physician or dermatologist can expedite the treatment process and improve patient prognosis., (© The Author(s) 2016.)

Scurvy results from a dietary deficiency of vitamin C (ascorbic acid) and is rarely thought of in modern day medicine. It now almost always occurs in pediatric patients with behavioral diagnoses, nutritionally restricted diets, and food allergies. Symptoms of scurvy include ecchymoses, bleeding gums, and arthralgias. Here, we present a 17-year-old male with autism spectrum disorder and a diet severely deficient in ascorbic acid due to textural aversion and food preferences. He presented with recurrent arthritis, hemarthrosis, bruising, and anemia. His vitamin C level was low, and his symptoms improved promptly after treatment with ascorbic acid., (© 2016 Wiley Periodicals, Inc.)

Scurvy was diagnosed in seven children at Boston Children's Hospital. All of the children had a developmental disorder and autism was the most common. They had a long-standing history of food selectivity with diets devoid of fruits and vegetables, and none of the children were supplemented with a multivitamin. They presented with limp, and an elaborate panel of tests and procedures were undertaken before the diagnosis of scurvy was made. Treatment with vitamin C led to rapid recovery of symptoms. This report emphasizes the importance of considering nutritional causes of musculoskeletal symptoms in children with autism and restrictive diets.

Scurvy, a vitamin C deficiency, was rampant during the age of discovery in Europe. In the mid-17th century, “Pasqua Rosée,” the first coffee house in London, put an ad in the newspaper “Publick Adviser” clearly stating, “It (coffee) is excellent to prevent and cure dropsy, gout, and scurvy.” A Netherlands trade merchant carried the information to Nagasaki, Japan, along with coffee beans harvested in the Netherlands’ new territory, Java Island. A Japanese physician in Nagasaki, Dr. Kai Hirokawa, translated the information into Japanese in his new book, “Dutch Medicines,” published in 1803. According to the ancient documents stored in Wakkanai City, Japan, the coffee beans were distributed to Tsugaru Clan soldiers who were guarding the northern coastline from 1855 to 1856. The purpose of the distribution was the prevention of scurvy and dropsy. As the result, none of the soldiers died from scurvy during the winter of 1855-1856. This paper discusses the pharmacological relationship between coffee micronutrients and vitamin deficiency syndrome.

Background: Scurvy is the classic and most severe form of vitamin C deficiency. This condition has become extremely rare among children in the industrialized countries., Patients and Methods: We report the case of two boys presenting bone pain associated with haemorrhagic gingivitis, with perifollicular purpura of the lower limbs in one boy. The children had an unbalanced diet. Scurvy was associated with vitamin D and iron deficiency. The dermatological and radiological abnormalities seen were characteristic and a favourable outcome was rapidly obtained following supplementation., Discussion: The possibility of this forgotten historical illness should not be overlooked in the presence of these dermatological and rheumatologic signs, since this can help avoid unnecessary or excessively aggressive investigations., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

A 45-year-old man presented with follicular exanthema in his lower limbs, alternating bowel habits and significant weight loss. His medical history included seronegative arthritis, bipolar disease and an inconclusive diagnostic laparoscopy. Diagnostic work up revealed microcytic anaemia and multivitamin deficiency. Skin biopsy of the exanthema suggested scurvy. Owing to these signs of malabsorption, upper endoscopy with duodenal biopsies was performed, exhibiting villous atrophy and extensive periodic acid-Schiff-positive material in the lamina propria, therefore diagnosing Whipple's disease (WD). After starting treatment with ceftriaxone and co-trimoxazole, an impressive recovery was noted, as the wide spectrum of malabsorption signs quickly disappeared. After a year of antibiotics, articular and cutaneous manifestations improved, allowing the patient to stop taking corticosteroids and antidepressants. This truly unusual presentation reflects the multisystemic nature of WD, often leading to misdiagnosis of other entities. Scurvy is a rare finding in developed countries, but its presence should raise suspicion for small bowel disease., (2015 BMJ Publishing Group Ltd.)

Scurvy, or vitamin C deficiency, is rarely presented to a rheumatology clinic. It can mimic several rheumatologic disorders. Although uncommon, it may present as pseudovasculitis or chronic arthritis. Scurvy still exists today within certain populations, particularly in patients with neurodevelopmental disabilities, psychiatric illness or unusual dietary habits.Scurvy presentation to the rheumatologist varies from aches and mild pains to excruciating bone pain or arthritis. Musculoskeletal and mucocutaneous features of scurvy are often what prompts referrals to pediatric rheumatology clinics. Unless health care providers inquire about nutritional habits and keep in mind the risk of nutritional deficiency, it will be easy to miss the diagnosis of scurvy. Rarity of occurrence as compared to other nutritional deficiencies, combined with a lack of understanding about modern-day risk factors for nutritional deficiency, frequently leads to delayed recognition of vitamin C deficiency. We report a case of scurvy in a mentally handicapped Saudi child, who presented with new onset inability to walk with diffuse swelling and pain in the left leg. Skin examination revealed extensive ecchymoses, hyperkeratosis and follicular purpura with corkscrew hairs, in addition to gingival swelling with bleeding. Clinical diagnosis of scurvy was rendered and confirmed by low serum vitamin C level. The patient did extremely well with proper nutritional support and vitamin C supplementation. It has been noticed lately that there is increased awareness about scurvy in rheumatology literature. A high index of suspicion, together with taking a thorough history and physical examination, is required for diagnosis of scurvy in patient who presents with musculoskeletal symptoms. Nutritional deficiency should also be considered by the rheumatologist formulating differential diagnosis for musculoskeletal or mucocutaneous complaints in children, particularly those at risk.

This paper reviews the rheumatological manifestations of scurvy, based on articles published in English from 1965 until October 2014, with a particular focus on rheumatological manifestations. Scurvy is a rare, uncommon disease in developed countries. Due to its clinical heterogeneity, the disease can easily mimic rheumatologic conditions leading to a delay in diagnosis and treatment.

Scurvy is rare in developed countries but is known to cause lower-extremity pain and refusal to ambulate in children. Since the discovery of the link between scurvy and dietary deficiency of ascorbic acid, there has been a substantial decrease in its prevalence and recognition. Here we describe 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.

A 49-year-old man presented to hospital with severe orthostatic hypotension, gingival dysplasia and a purpuric rash involving his extremities. The orthostatic hypotension failed to respond to fluids and, on the basis of physical examination and dietary history, the patient was given a preliminary diagnosis of scurvy (ascorbic acid deficiency). Serum ascorbic acid levels were undetectable and the orthostasis was resolved within 24 h of ascorbic acid replacement. The pathogenesis of orthostatic hypotension in the setting of scurvy appears to involve impaired catecholamine synthesis and attenuated vasomotor response to α-adrenergic stimulation. We believe that this case describes a rare presentation of scurvy and highlights a previously under-reported connection between scurvy and vasomotor instability., (2014 BMJ Publishing Group Ltd.)

Vitamin C deficiency is rare in developed countries but there is an increased prevalence in chronic alcohol abusers. In the UK, it is common practice to treat patients with chronic alcoholism who are admitted to hospital with intravenous vitamins B1, B2, B3, B6 and C for 2-3 days, followed by oral thiamine and vitamin B-compound tablets. This is a case of a 57-year-old man with a history of chronic alcoholism and chronic obstructive lung disease who was admitted to the intensive care unit for pneumonia requiring ventilatory support. He was given high doses of intravenous vitamins B1, B2, B3, B6 and C for 3 days then oral thiamine and vitamin B compound tablets but developed scurvy 4 days later. He was restarted on oral vitamin C supplementation and showed signs of improvement within 3 days of treatment.

Scurvy, a disease caused by a deficiency of ascorbic acid (vitamin C), is not very common disease especially in pediatric age. In the late nineteenth century, instead, we assisted to increase incidence of this problem for the use of heated milk and convenience foods. We report two cases of scurvy: a child of 3 years old came to our observation for an important gums' stomatitis, fever, widespread petechiae and ecchymosis on the skin of the lower limbs; in the second moment he had pain in upper and lower limbs with difficulty in walking; a second child of 4 years came to our observation for pain lower limbs and maintained the posture of the legs down, inability to walking, with reduced muscle tone and trophism in all limbs; at the instrumental examination he had an alveolar hemorrhage. The two boys had a history of a diet completely lacking in fruits and vegetables; they were drinking almost only milk. They carried various laboratory and instrumental tests, in particular X-ray of lower limbs that showed "a thick sclerotic metaphyseal line with beak-like excrescences of tibiae and femur". The characteristic radiological appearance, the particular clinical aspects, the dietary history and the dosage of vitamin C, have led us to the diagnosis of scurvy. They started therapy with vitamin C and they had a progressive improvement in general condition.

Periodic transfusions and effective chelation have ensured that thalassemics survive in to adulthood but their life is punctuated by peculiar problems in adulthood. Three cases of scurvy are being reported presenting uniquely as purpura, right hip joint effusion and right knee joint effusion with haemorrhage in prepatellar and retropatellar bursae, respectively over an 18 month period (2009-2010). The first two cases did give a history of gum bleed. None had any coagulation disturbance or transfusion-transmitted infections or connective tissue disorder. All the three cases responded dramatically to vitamin C supplementation. It is imperative to keep in mind that recurrent blood transfusions are associated with a state of subclinical vitamin C deficiency and overt scurvy may manifest as cumulative number of transfusions increase, as in adult thalassemics.

Pediatric scurvy is a rare condition characterized by perifollicular petechiae and bruising, hemorrhagic gingivitis and musculoskeletal symptoms, all assumed to be predominantly related to abnormal collagen structure. We report on a 9-year-old autistic boy with vitamin C deficiency due to a highly limited food range presenting with multiple petechiae, gum bleeding and debilitating bone pain, in whom platelet aggregometry revealed a distinctly reduced thrombocyte aggregation, normalizing after vitamin C supplementation. This observation indicates that platelet dysfunction may additionally contribute to the hemorrhagic diathesis in scurvy, and demonstrates that ascorbic acid deficiency should be considered in children with an otherwise unexplained acquired thrombocytopathy., (© Georg Thieme Verlag KG Stuttgart · New York.)

Scurvy is caused by prolonged dietary deficiency of vitamin C, the plasma concentration of which appears inversely related to mortality from all causes. Its clinical importance relates principally to its role as a cofactor in a number of enzyme reactions involved in collagen synthesis, dysfunction of which disrupts connective tissue integrity, resulting in impaired wound healing and capillary bleeding. In the UK, overt scurvy is diagnosed only rarely. However, subclinical vitamin C deficiency appears quite common, one study estimated that 25% of men and 16% of women in the low income/materially deprived population had vitamin C deficiency, with smoking a strong predictor. Because many of the early symptoms of vitamin C deficiency (fatigue, malaise, depression and irritability) are non-specific, the diagnostic possibility of scurvy is usually delayed until haemorrhagic manifestations occur. The classical cutaneous features consist of perifollicular purpura, contorted (corkscrew) hairs and follicular hyperkeratosis, particularly affecting the legs. Large areas of purpura or ecchymosis may occur. Swelling and bleeding of the gums is an early mucosal symptom, and progressively severe gum disease causes loss of teeth. Subperiosteal haemorrhage, particularly in the femur and tibia, can present as pain, pseudoparalysis, swelling and discoloration of the legs. Haemorrhage into joints and muscle is very uncomfortable. Diagnosis is generally made on the basis of clinical features, corroborated by a history of dietary inadequacy, and the subsequent rapid resolution of symptoms with the restoration of an adequate vitamin C intake.

We describe the case of a 40-year-old female patient who developed severe pulmonary hypertension and life-threatening right-sided heart failure in association with dietary scurvy and iron deficiency. Supplementation with oral vitamin C and iron very likely contributed to her complete cure. Scurvy-associated pulmonary arterial hypertension could result from impaired availability of endothelial nitric oxide, but inappropriate activation of the hypoxia-inducible family (HIF) of transcription factors could play an even more important role. HIF coordinates the body's responses to hypoxia, and its activity is regulated by oxygen-dependent prolyl hydroxylases, which need vitamin C and iron as cofactors. Deficiency of these cofactors could lead to uncontrolled HIF activity and pulmonary vasoconstriction responsive to vitamin C and iron administration.

We report a case of chronic glossitis in a 4-year-old boy due to scurvy. The boy showed up in our department with a patchy depapillated tongue. A detailed dietary history revealed an unbalanced diet without any fruit or vegetable. The biological investigations showed a low serum ascorbic acid. The boy was treated by oral ascorbic acid during 15 days. The glossitis improved within one week and serum levels of vitamin C returned to the normal range. In industrial countries, scurvy became a rare disease in healthy children. However, since a few years, cases are reported in children and teenagers with unbalanced diet coming from economically favoured families. These extreme cases are one of the signs of a more general deterioration of dietary habits in paediatric populations in our societies. This emphasizes the importance of effective nutritional education programs aimed towards both parents and children.

Objectives: To report 3 cases of scurvy seen in a large urban medical center over a 6-month period, referred for evaluation of rheumatologic symptoms and findings in the presence of elevated inflammatory markers. The relevant literature is reviewed and unusual manifestations highlighted., Methods: Descriptive case reports of 3 patients ultimately diagnosed with scurvy and a review of the relevant literature with an emphasis on rheumatologic manifestations (PubMed search, 1965 through August 2009)., Results: Three patients presented with symptoms including fatigue, purpuric rash, synovitis with effusion, anemia, and markedly elevated erythrocyte sedimentation rate and C-reactive protein levels. One patient presented with severe pulmonary hypertension. Careful nutritional history revealed a diet deficient in vitamin C. Examination revealed hemarthrosis, skin findings characteristic of scurvy, and deficiency in vitamin C on laboratory analysis. Symptoms resolved with vitamin C supplementation. Characteristics and frequency of rheumatologic manifestations are reviewed., Conclusions: While scurvy is usually described in poorer countries, individuals who have psychiatric disorders, or alcoholics with poor nutrition, it can occur even in otherwise normal populations in affluent countries. Such patients often present to rheumatologists with rheumatologic symptoms and awareness of the disease is necessary to make the proper diagnosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Scurvy is well known since ancient times, but it is rarely seen in the developed world today owing to the discovery of its link to the dietary deficiency of ascorbic acid. It is very uncommon in the pediatric population, and is usually seen in children with severely restricted diet attributable to psychiatric or developmental disturbances. The condition presents itself by the formation of perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We report a case of scurvy in a 10-year-old developmentally delayed boy who had a diet markedly deficient in vitamin C resulting from extremely limited food choices. He presented with debilitating bone pain, inflammatory gingival disease, and perifollicular hyperkeratosis. The diagnosis was made based on clinical and radiographic findings. The importance of diet history is emphasized. We present this case with the aim to help the clinician identify scurvy and implement treatment for a potentially fatal but easily curable disease.

Scurvy, or hypovitaminosis C, is an uncommon condition that exists today primarily within certain unique populations-particularly the elderly subjects, patients with neurodevelopmental disabilities or psychiatric illnesses, or others with unusual dietary habits. Vitamin C is an essential nutrient in the human body, and is important in synthesizing collagen factor whose faulty production is responsible for most of the clinical manifestations of scurvy. These clinical manifestations can include dystrophic or corkscrew hairs, gingival hyperplasia, and weakened blood vessel walls, causing bleeding in the skin, joints, and other organs. Although rare in the Unites States, the presence of scurvy should not be forgotten because of its presence among susceptible populations. Moreover, with its diagnosis, treatment and cure is one of the simplest in modern medicine. We report a case of scurvy in a 10-year-old autistic child., (© 2010 Wiley Periodicals, Inc.)

We report on a 13-month-old boy who experienced pain while mobilising, and had bruising and swelling of the lower limbs. Laboratory examinations revealed anaemia and skeletal x-rays showed irregularity and thickening of the provisional zones of calcification of lower and upper limbs. The boy had been fed with only goat milk, homogenised meat, fruits and vegetables, all of which had been boiled together. Forty-eight hours after starting oral vitamin C supplementation, the patient showed dramatic clinical improvement. The clinical presentation, laboratory and imaging findings, together with the good response to vitamin C intake, allowed us to confirm the diagnosis of infantile scurvy. Scurvy is a disease that can be found among children, especially among groups with restrictive eating pattern. Fortunately, once diagnosed, scurvy is an easily treatable disease by administration of vitamin C and a correct diet that is rich in fruits, vegetables and fresh meat, all of which contained vitamin C.

We report the case of the case of a 56 year old female with sepsis on a background of rheumatoid arthritis and steroid use manifesting with overt clinical features of scurvy. Ascorbic acid assays were able to demonstrate severe deficiency and confirm a diagnosis of scurvy. Clinical resolution of signs and symptoms following commencement of vitamin C replacement was rapid. The intensivist and dietitian need to consider this diagnosis even in the first world setting, particularly in the presence of sepsis, inflammatory conditions, steroid use and importantly malnutrition., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

A diet restricted to rice and boiled fruit and vegetables leads to vitamin C deficiency. We describe the third case, to our knowledge, of retinal hemorrhages related to scurvy. Reduced bilateral visual acuity in a 50-year-old patient was associated with macrocytic anemia, denutrition, and cutaneous ecchymoses. Oral vitamin C treatment provided subjective clinical improvement and regression of the retinal hemorrhages on fundus examination, with no side effects. Vitamin C plays an important role in collagen stability in vascular and bone walls., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Scurvy has become rare in modern societies, but should be considered in malnourished persons, alcoholics, and in infants on unsupplemented milk diets who present with musculoskeletal pain or a bleeding tendency. The diagnosis of scurvy can be challenging because of the rare incidence and vague and nonspecific early symptoms. We report here a case of scurvy in a young boy who presented with an inability to walk and severe musculoskeletal pain. The diagnosis was established based on his clinical picture, radiological appearance, and low serum level of vitamin C. The patient responded well to vitamin C supplementation with full resolution of his symptoms. He regained his ability to walk and his family was happy and satisfied with the outcome of treatment. Although the incidence of scurvy has become low in Saudi Arabia, it can still occur and early recognition is important because of the excellent prognosis.

A 68-year-old female with an extensive history of unexplained problems presented at the Department of Internal Medicine for an analysis of painful cutaneous abnormalities of the lower legs. A systemic cause could not be found. Later on the general practitioner noted haematoma and petechiae and subsequently a hypovitaminosis C. The patient received active vitamin C supplement for this. The cutaneous abnormalities on the legs had significantly improved after 3 weeks. This patient was found to have symptomatic hypovitaminosis C, also known as scurvy, as a complication of an psychiatric disorder. Although scurvy might appear to be a disease of the past that rarely occurs nowadays, it should nevertheless be given due consideration. This requires a good history taking.

Although ascorbic acid is an important water-soluble antioxidant and enzyme cofactor in plants and animals, humans and some other species do not synthesize ascorbate due to the lack of the enzyme catalyzing the final step of the biosynthetic pathway, and for them it has become a vitamin. This review focuses on the role of ascorbate in various hydroxylation reactions and in the redox homeostasis of subcellular compartments including mitochondria and endoplasmic reticulum. Recently discovered functions of ascorbate in nucleic acid and histone dealkylation and proteoglycan deglycanation are also summarized. These new findings might delineate a role for ascorbate in the modulation of both pro- and anti-carcinogenic mechanisms. Recent advances and perspectives in therapeutic applications are also reviewed. On the basis of new and earlier observations, the advantages of the lost ability to synthesize ascorbate are pondered. The increasing knowledge of the functions of ascorbate and of its molecular sites of action can mechanistically substantiate a place for ascorbate in the treatment of various diseases.

We report an unusual case of scurvy where a six-year-old female presented with clinical and radiological features suggestive of juvenile idiopathic arthritis. However, follow-up radiological examination, carried out in view of refractory arthritis, was diagnostic for scurvy and the patient later responded well only with vitamin C therapy.

A 5 year old female developed features of complex regional pain syndrome (CRPS) i.e excessive pain to touch, decreased sweating and edema of left ankle 2 years after fracture of left tibia. Gum bleeding, petechiae and pseudoparalysis and suggestive radiograph characterized scurvy. Hyperesthesia improved and child walked with support following administration of vitamin C.

Scurvy is a rare disease occurring because of a nutritional deficiency of vitamin C. In the paediatric age group the disease is usually characterized by musculoskeletal manifestations. Treatment is straightforward and consists of vitamin C administration. However, if the patient is left untreated, scurvy may be life-threatening. We report here the case of a 16-month-old infant with scurvy. After proper treatment, the complaints disappeared in a very short time period and the boy grew up as a completely normal child during the 12 years follow-up. Nowadays only few physicians have experience with this disease, and ascorbic acid deficiency can thus easily be overlooked. With this paper we aimed to remind of the efficacy of vitamin C administration for patients with scurvy.

The literature on the content and stability of vitamin C (ascorbic acid, AA) in citrus juices in relation to industrial practices is reviewed. The role of vitamin C from citrus juices in human diet is also reviewed. Citrus fruits and juices are rich in several types of bioactive compounds. Their antioxidant activity and related benefits derive not only from vitamin C but also from other phytochemicals, mainly flavonoids. During juice processing, temperature and oxygen are the main factors responsible for vitamin C losses. Non-thermal processed juices retain higher levels of vitamin C, but economic factors apparently delay the use of such methods in the citrus industry. Regarding packing material, vitamin C in fruit juice is quite stable when stored in metal or glass containers, whereas juice stored in plastic bottles has a much shorter shelf-life. The limiting step for vitamin C absorption in humans is transcellular active transport across the intestinal wall where AA may be oxidized to dehydroascorbic acid (DHAA), which is easily transported across the cell membrane and immediately reduced back to AA by two major pathways. AA bioavailability in the presence of flavonoids has yielded controversial results. Whereas flavonoids seem to inhibit intestinal absorption of AA, some studies have shown that AA in citrus extract was more available than synthetic ascorbic acid alone. DHAA is reported to possess equivalent biological activity to AA, so recent studies often consider the vitamin C activity in the diet as the sum of AA plus DHAA. However, this claimed equivalence should be carefully reexamined. Humans are one of the few species lacking the enzyme (L-gulonolactone oxidase, GLO) to convert glucose to vitamin C. It has been suggested that this is due to a mutation that provided a survival advantage to early primates, since GLO produces toxic H2O2. Furthermore, the high concentration of AA (and DHAA) in neural tissues could have been the key factor that caused primates (vertebrates with relative big brain) to lose the capacity to synthesize vitamin C. Oxidative damage has many pathological implications in human health, and AA may play a central role in maintaining the metabolic antioxidant response. The abundance of citrus juices in the Mediterranean diet may provide the main dietary source for natural vitamin C.