**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].
