Vitamin C Deficiency

Abstract

The health of the body is strongly influenced by the nutrients in food, including vitamins and minerals crucial for supporting energy levels and overall stability. Vitamin C, in particular, plays a significant role in the body’s ability to resist contamination from heavy metals present in consumed food, thereby affecting the organ’s capacity to defend against such attacks. Failure to address contamination can lead to deteriorating health, causing symptoms such as headaches, convulsions, weight loss, allergies, cognitive impairment, skin issues, and conditions affecting the central nervous system. Various risk factors contribute to vitamin C deficiency, including alcoholism, infants exclusively fed cow’s milk, elderly individuals consuming a limited diet of tea and toast, financial constraints preventing access to fruits and vegetables, smoking, eating disorders, type 1 diabetes with increased vitamin C needs, gastrointestinal disorders like inflammatory bowel disease, iron overload resulting in the kidneys wasting vitamin C, restrictive diets, and food allergies.

1. Introduction

1.1 Muscle weakness

L-ascorbic acid (AsA), commonly known as vitamin C, is a water-soluble antioxidant vitamin that has the potential to combat Reactive Oxygen Species (ROS) such as hydroxyl radicals, singlet oxygen, and superoxide radicals, which can compromise muscle health. Skeletal muscle consists of thousands of fibers, each with its own morphology and function. Muscles operating under optimal physical conditions exhibit reduced fatigue response. However, the substantial production of ROS during strenuous activity can lead to damage to biomolecules like proteins, lipids, and DNA, as well as muscle autofluorescence. Additionally, elevated oxygen levels associated with conditions like sarcopenia contribute to muscle aging and disease.

Studies on animals with decreased levels of vitamin C have shown an increase in oxygen levels and carbon protein production. When vitamin C levels are low, performance declines in muscles such as the gastrocnemius, soleus, plantaris, tibialis anterior, and extensor digitorum longus (EDL), resulting in performance decreases of 74%, 83%, 77%, 74%, and 76%, respectively. Conversely, maintaining adequate levels of vitamin C can help prevent muscle disease [1, 2, 3].

Vitamin C is crucial for bone health, and its deficiency is often observed in patients with impaired bone nutrition, which can increase the risk of osteoporosis. Reduced intake of fresh fruits and vegetables leads to a decline in the body’s vitamin C levels. Ascorbic acid plays a vital role in carbohydrate metabolism, melanin synthesis, and the regeneration of vitamin E and glutathione, thereby enhancing nutrient absorption. It is recommended that women consume 65 mg of vitamin C daily and men consume 75 mg [4].

Low levels of vitamin C can elevate the risk of osteoporosis, especially in individuals with inflammatory bowel disease (IBD). In IBD patients, there is an increased risk of tumor necrosis factor α (TNF-α) levels, partly due to varied nutrient intake, including vitamin C. Research indicates that many children diagnosed with IBD have low serum vitamin C levels. Addressing this deficiency by consuming adequate vitamin C can help reduce the risk of osteoporosis by as much as 33% [5].

The absorption of vitamin C in the digestive tract typically ranges from 70–90% of the total amount consumed, especially when intake is around 200 mg. However, if intake surpasses 1250 mg, absorption decreases to around 30%, occurring through diffusion or active transport mechanisms. Vitamin C deficiency can result in scurvy, characterized by symptoms such as gingival swelling, tooth loss, ecchymosis, delayed wound healing, fatigue, vision issues, and neurological complications. These manifestations are often linked to alterations in the extracellular matrix of bones, blood vessels, and tendons, leading to bone fragility and hemorrhaging [4].

Maintaining the stability of essential nutrients is crucial for enhancing resistance against diseases like premature aging. Vitamin C is particularly vulnerable to loss due to factors such as poor food quality, advancing age, smoking, and alcohol consumption. A decrease in vitamin C levels leads to a decline in overall performance and affects blood plasma levels. In India, there is a notable decrease in the percentage of vitamin C in blood with age, correlating with a reduction in the nutritional value of the diet [6].

Fruits and vegetables serve as the primary sources of vitamin C intake in the body. Vitamin C plays a role in neutralizing heavy metals like iron and copper. Deficiency in vitamin C increases the risk of malnutrition and scurvy [7].

A deficiency in AsA or vitamin C leads to skeletal muscle weight loss, fiber atrophy, and reduced physical performance. This deficiency heightens the risk of ROS impacting skeletal muscle endurance, cellular function, and gene expression [3].

Vitamin C stored in the body lasts for approximately five months in adolescents. However, if this vitamin is depleted, clinical symptoms such as gingivitis, tooth loss, swelling in the lower extremities, and perifollicular hemorrhages may occur. Additional symptoms include sensations of alternating hot and cold, dizziness, lightheadedness, excessive sweating, hemorrhagic spots in the eyes, dry skin, excessive keratosis, curly body hair, and impaired wound healing [8].

1.2 Hampered wound healing

Vitamin C serves as a co-substrate in numerous enzyme reactions within the body. It is essential for the synthesis of collagen, a crucial protein in connective tissues, and aids in wound healing. Unlike plants and certain animal species, humans lack the enzyme gulonolactone oxidase necessary for synthesizing their own vitamin C. Therefore, humans must obtain vitamin C from dietary sources such as fruits and vegetables.

Deficiency in vitamin C can lead to various diseases, such as impaired wound healing (scurvy), which can manifest as bleeding, swelling due to weak muscles, and fatigue. If left untreated, scurvy can progress to more severe symptoms, including skin discoloration and irritation.

Research indicates that the average prevalence of vitamin C deficiency among adolescents is around 7.1%, with levels below 11.4 μmol/L in some studies and below 11 μmol/L in others. Currently, recommended levels of vitamin C in the body range from 11 to 40 μmol/L or ≥ 11 to 28 μmol/L. However, it is noteworthy that approximately one-fifth of the population in the United Kingdom is deficient in vitamin C, even at optimal levels [9].

Scurvy is a disease caused by insufficient intake of vitamin C. In Ireland, there has been a decrease in vitamin C consumption due to changes in potato consumption patterns. Initially, potatoes were a staple, but processing methods have led to a 20–40% reduction in their vitamin C content. Fresh potatoes contain a vitamin C concentration similar to apples, pears, or even oranges and lemon juice, averaging around 40–50 mg/100 g.

Adequate vitamin C intake is crucial for various bodily functions, including the maturation of collagen, a protein essential for tissue, skin, cartilage, and bone formation. According to a report from the World Health Organization and the Food and Agricultural Organization of the United Nations (2004), children should consume at least 45 mg of vitamin C daily, with a minimum intake of 10 mg per day. Generally, men require more vitamin C than women due to differences in hormonal metabolism [8].

Persistent loss and deficiency of vitamin C can significantly increase the risk of scurvy. Additionally, insufficient levels of vitamin C can lead to hypovitaminosis, where plasma concentration drops below standard levels. Research shows that approximately 10% of the population in the Western world suffers from hypovitaminosis, with plasma concentrations around 23 μM.

Furthermore, vitamin C deficiency is associated with brain disorders and can affect processes such as antioxidant metabolism and degradation [10].

Patients with inflammatory conditions and compromised immunity greatly benefit from vitamin C supplementation, as it aids in wound healing and enhances immune function [11]. Vitamin C serves vital physiological functions that support immune health and overall wellbeing. Adequate levels of vitamin C contribute to improved wound healing and respiratory processes.

Consistently low levels of vitamin C in patients can alter genetic expression, rendering the body more susceptible to various diseases. A deficiency in vitamin C impairs the body’s ability to manage antioxidants and weakens resistance to air pollution [12]. Furthermore, low serum levels of vitamin C can lead to death, with smokers being at greater risk due to increased antioxidant activity, which can compromise respiratory function [12].

Diabetes mellitus often leads to delayed wound healing due to heightened oxidative pressure mechanisms. ROS, such as superoxide anions, can decrease insulin production and impair insulin signal transduction activity. Early intervention with sufficient vitamin C supplementation can help mitigate ROS levels before diabetes onset. Vitamin C deficiency exacerbates the situation, leading to increased ROS-induced inflammation in wounds among individuals with diabetes mellitus [13].

1.3 Weakened immune system

The decline in vitamin C levels in the body correlates with weakened immunity. Oxygenation ability is hindered, disrupting normal bodily reactions, as the process of DNA transcription is impeded. Gradual decline in vitamin C levels can lead to distress and potential rupturing of blood vessels. In the brain, vitamin C plays a pivotal role in regulating redox balance and increasing the risk of damage from the secretion of dopamine and glutamate. The concentration of vitamin C in the brain needs to remain stable at levels approximately 100-fold higher than those found in plasma. The brain has a greater capacity to maintain adequate vitamin C levels compared to deficiency, as vitamin C supplementation can be efficiently transported across the choroid plexus and into neurons [14].

Crohn’s disease is impacted by imbalances in vitamins and minerals, especially vitamin C. Serum vitamin C levels are expected to range from 22–70% and 15–84% in individuals with Crohn’s disease. Studies have shown prolonged deficiencies in vitamin C to be implicated in the development of Crohn’s disease, particularly in women.

Patients aged 47–58 years are susceptible to diseases such as Crohn’s disease, Hashimoto’s thyroiditis, and quiescent Sjogren’s syndrome. In one case, a patient in this age group presented to the clinic with gum bleeding for several months but denied recent changes in gastrointestinal symptoms. She had been following a diet of low-residue, low-fermentable oligo, di, and monosaccharides, and polyols, and her Crohn’s had remained in remission after remote surgery. Physical examination revealed gingival swelling and bleeding, as well as a slightly distended abdomen, but was otherwise unremarkable. Laboratory tests, including complete blood count, complete metabolic panel, iron studies, thyroid studies, vitamin D, vitamin B12, and folate, were all normal. However, her vitamin C level was found to be below 5 mmol/L. She was initiated on 100 mg of ascorbic acid three times a day, and her symptoms resolved within a few weeks. Unfortunately, she did not return for a follow-up, so her vitamin C levels could not be rechecked to confirm adequate supplementation [15].

Vitamin C is an essential nutrient that must be obtained through diet to prevent both deficiencies, like scurvy, and potential tissue damage from excessive intake. The body’s vitamin C levels are influenced by dietary intake, efficient absorption, recycling, and renal reuptake. Sodium-dependent vitamin C transporters (SVCTs) control vitamin C concentrations in blood and tissues. Different tissues have varying vitamin C requirements, with the highest concentrations found in the brain, adrenal glands, and pituitary glands. These concentrations reflect the specific needs of each tissue, as vitamin C serves as a cofactor for various biosynthetic and regulatory metalloenzymes, including those involved in catecholamine hormone synthesis and peptide regulation. Vitamin C also regulates more than 100 genes in the body, supporting overall health and resistance to diseases [16].

Vitamin C deficiency can affect pharmacokinetics differently in boys and girls. Recent discoveries highlight the crucial role of vitamin C in epigenetics, essential for the growth and development of infants and children. Generally, vitamin C requirements are adjusted based on body weight in infants and children. In America, children are typically provided with vitamin C doses aiming to achieve levels exceeding 71 μmol/L, with a decrease observed in 1.6% of children. Studies in Mexico reveal that a significant proportion of school-age children experience deficiency or hypovitaminosis of vitamin C, with average concentrations ranging from 28 to 24 ± 9 μmol/L. Hypovitaminosis C affects approximately 38% of these children, while 23% exhibit vitamin C deficiency. This is attributed to an average daily intake of around 44 mg/day of vitamin C through diet. It should be noted that meeting the required concentration of vitamin C in the body necessitates a diet rich in fruits and vegetables [16].

Pregnant women are particularly susceptible to experiencing declines in vitamin C levels. Research suggests that vitamin C deficiency increases the risk of various health conditions including cardiovascular diseases, cancer, diabetes, and fatty liver. Stressful conditions can deplete vitamin C levels in the brain, leading to early symptoms such as mood disorders and depression, and disrupting DNA improvement [10].

One of the primary factors contributing to inflammation and obesity is low level of vitamin C, which impairs antioxidant metabolism. Obese women tend to have vitamin C levels 44% lower compared to those with normal weight. Poor habits such as low consumption of fruits and vegetables can further reduce nutrient absorption due to vitamin C deficiency. However, routine consumption of 1000 mg/day of vitamin C significantly reduces the risk of diabetes, abnormal insulin levels, triglycerides (TGs), and low-density lipoprotein (LDL). Vitamin C also plays a significant role in reducing inflammation in the body [17].

A weakened immune system coupled with declining levels of vitamin C in the brain can quickly impact the performance of other organs. Normally, the body can counteract oxidative stress with a certain quantity of antioxidants. However, disturbances in antioxidant metabolism due to low levels of vitamin C can lead to conditions such as diabetes. Vitamin C is known to be crucial for brain health, playing important roles in neuroprotection, neurotransmission, and neuromodulation. Deficiency in vitamin C can result in abnormal phenotypes, leading to disabilities in young individuals, disrupted performance, hypersensitivity to dopamine or allergens, and severe impairment of brain function [18].

Deficiency of vitamin C has been reported to increase susceptibility to the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Symptoms of this disease include fever, tachycardia, weakness, and lymphadenopathy. A decrease in immunity is the main factor allowing the parasite to damage skin tissue, leading to the development of Chagas disease, specifically due to the presence of ROS and reactive nitrogen species (RNS) [19].

Additionally, vitamin C deficiency can disrupt ovarian function, impairing ovary regeneration and hormone paracrine function, inhibiting cell growth in the ovary and epithelial cells, and degrading immune response [20].

Administration of vitamin C at doses of 66 mg/kg/h for 24 hours has been associated with pneumonia, while doses ranging from 500 mg to 8 g per day have been recommended. Periodic intake of vitamin C can help reduce fever, promote healthy skin, and alleviate chest pain [21].

On average, the body loses approximately 30–60 mg of vitamin C daily, with absorption rates leading to a blood plasma concentration of around 33 μM. Low levels of vitamin C can increase the risk of various health conditions, including cancer (e.g., lymphoma, leukemia), glaucoma, and acute coronary syndrome in women. Additionally, vitamin C deficiency can lead to the failure of carnitine synthesis, disruptions in gene transcription and translation mechanisms, decreased production of tyrosine hormones, diminished protection against ROS, and reduced absorption of iron in the gastrointestinal tract [5].

1.4 Vitamin C deficiency in fish

Vitamin C plays a crucial role in the physiological function of various animal species, including fish [22]. The vitamin C requirements of fish are influenced by factors such as size, age, growth rate, environmental conditions, and nutritional needs. Different species of fish may require varying levels of vitamin C. Deficiency in vitamin C can lead to reduced survival rates, lipid accumulation, skeletal deformities, decreased activity of specific enzymes, reduced tissue vitamin storage, lower liver lipid content, decreased hepatosomatic index, and diminished expression of heat shock proteins, ultimately affecting growth performance [23].

Loss of vitamin C at certain levels can result in decreased vitality and nutrient absorption in fish. Vitamin C supplementation significantly reduces the risk of stress in fish and promotes reproductive success by aiding in the synthesis of fats necessary for vitellogenesis [24].

Vitamin C deficiency in fish impairs their ability to neutralize free radicals found in water, as vitamin C is crucial for preventing lipid peroxidation in blood plasma. This deficiency leads to a decline in the fish’s resistance against bacterial attacks, as its immune system becomes compromised. Reduced levels of vitamin C significantly diminish phagocytic activity, antibody degradation, and lysozyme activity in fish [22].

In tilapia, vitamin C deficiency increases susceptibility to bacterial attacks, such as from Aeromonas hydrophila, reduces resistance to environmental changes, and increases stress levels, ultimately leading to higher mortality rates [25].

Deficiency of vitamin C in fish is influenced by factors such as temperature, oxygen levels, pH, light exposure, and diet composition. The nutrient requirement for vitamin C in tilapia is around 50 mg/kg-1 [26].

The effects of vitamin C deficiency in fish include weight loss, reduced specific growth rate, and decreased survival rates of Nile tilapia fingerlings. Additionally, deficiencies lower the quality of fish in terms of nutrient absorption from feed, increase the risk of hemorrhage during bacterial infections, reduce blood and plasma volume, lower protein conversion efficiency and protein efficiency ratio, and decrease oxygen consumption levels [26].

The absence of vitamin C can lead to damage in vital organs such as the gills, kidneys, liver, and scales, making fish more susceptible to injury. Furthermore, it can contribute to higher ammonia production in fish [27].

Vitamin C is essential for maintaining various functions in fish, including the absorption of ions in water, maintaining strong bone structure, and preventing skin irritations and bleeding. Skin irritations are often observed when there is a decrease in vitamin C levels in the blood, as it impairs the synthesis of collagen [28].

Moreover, vitamin C deficiency can lead to a decrease in hormones’ self-defense activity and the proteomic activity of hemocytes. Additionally, deficiencies in vitamin C may lessen the function of enzymes such as phenoloxidase and reduce the effectiveness of antiviral agents, antimicrobial proteins, agglutinins, and hemolysins [29].

Deficiency of vitamin C can lead to various negative effects on fish health and immune function. Roosta et al. [30] reported that vitamin C deficiency can lower the activity of self-defense hormones and the proteomic activity of hemocytes. Additionally, it can reduce the function of enzymes such as phenoloxidase, antivirus agents, antimicrobial proteins, agglutinins, and hemolysins.

Gao et al. [22] highlighted that red sea bream (Pagrus major) experience decreased phagocytic activity, antibody levels, and lysozyme activity when their vitamin C needs are not met. Similarly, Ibrahem et al. [25] found that low levels of vitamin C result in decreased feed efficiency and metabolic assimilation of dietary nutrients in fish, leading to retarded growth, darkening of the skin, anorexia, and high mortality in fish such as parrotfish (Oplegnathus fasciatus) [31].

Furthermore, Wu et al. [32] observed that vitamin C deficiency in white shrimp (Litopenaeus vannamei) leads to a decrease in antioxidant levels and cofactors in enzyme reactions, reducing the non-specific immune response against bacterial infections and the synthesis of collagen for tissue repair. In juvenile cobia (Rachycentron canadum), a deficiency in vitamin C leads to decreased activities of lysozyme serum, superoxide dismutase (SOD), alkaline phosphatase (AKP), and total immunoglobulin (Ig) [33].

2. Conclusion

L-ascorbic acid (also known as AsA or vitamin C) is a water-soluble vitamin with antioxidant properties. Its stability is essential for increasing resistance against various diseases, including premature aging, skeletal muscle weight loss, fiber atrophy, and decreased physical performance. A deficiency in vitamin C significantly reduces phagocytic activity, antibody levels, and lysozyme activity, which are crucial components of the body’s immune response.