INL Article - Why Vitamin C for Infections
Why Give High Dose Vitamin C During Infections?
Vitamin C is a critical micronutrient with many sites of action within the body including various cellular processes within the innate and adaptive immune system and its dietary deficiency is more common than expected in the modern world.
Most people in Hong Kong just about manage the 100mg of vitamin C required to function daily. However, "prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100 – 200mg/day), which optimise cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand." (1)
Epidemiological studies have demonstrated that hypovitaminosis C (plasma vitamin C <23 umol/L) is relatively common in western populations, and vitamin C deficiency (<11 umol/L) is the fourth leading nutrient deficiency in the USA. (2)
Why is vitamin C needed in acute infections?
Vitamin C levels in white blood cells, especially phagocytic cells, are tens of times higher than in plasma. Vitamin C has been shown to affect the reactive oxygen species (ROS) functions of phagocytes, and for the production of antiviral interferon both aiding antiviral effects (3). Vitamin C has also been shown to energise neutrophil migration to the site of infection, driving phagocytosis and oxidant generation, and microbial clearance.
Also ascorbate assists the maturation of T-lymphocytes. (4)
Many infections lead to the activation of phagocytes, with the release of reactive oxygen species (ROS). The phagocytic neutrophils and macrophages are primed for enhanced superoxide generation when activated by infection. This ROS plays a role in the processes that lead to the deactivation of viruses and the killing of bacteria. However, many of the ROS produced appear to be harmful to the host cells, and in some cases they seem to play a role in the pathogenesis of infections, including loss of CD4+ cells in chronic infections such as HIV. However, the macrophages have a defense to this effect by concentrating, then protectively utilising and recycling ascorbate. (5)
Ascorbate recycling occurs in active phagocytes when extracellular ascorbate is oxidized under the ROS activity, transported back as dehydroascorbic acid, and reduced intracellularly to ascorbate. This reduction process requires adequate glutathione, vitamin E and possibly lipoic acid. Induction of phagocytic activity by bacteria and fungi resulted in as high as a 30-fold increase in intracellular ascorbate compared with neutrophils not exposed to microorganisms. (6) Clearly ascorbate is demanded by phagocytes when actively engaged in infection, and for optimal levels to be maintained glutathione is especially needed.
ROS play a role in the deactivation of viruses. However, many of the ROS are harmful to the host cells and may be involved in the pathogenesis of viral induced host injury. The figure gives an indication of the intracellular nutrients required by phagocytes, especially vitamin E and glutathione help recycle vitamin C during infection and related ROS activation.
Respiratory syncytial virus (RSV) is one of the most important causes of upper and lower respiratory tract infections in infants and young children. RSV infection of airway epithelial cells induces ROS production with inhibition of lung antioxidant enzymes; this oxidant-antioxidant cellular imbalance plays a major role in RSV pulmonary toxicity. (7)
Vitamin C is a potent antioxidant, which directly scavenges oxygen free radicals as well as restoring other cellular antioxidants including tocopherol and glutathione. Vitamin C and glutathione may ameliorate viral-induced oxidative injury, which can otherwise affect mitochondria and play a role in post viral fatigue syndromes.
Our Recommended Vitamin C for Acute Infections
INL recommends Orthoplex Clinical C, as the formula has all the nutrients required to recycle the dehydroascorbic acid back to ascorbate, allowing vitamin C to remain longer as an antioxidant. Also, as the diagram above indicates on the left side, these ROS scavengers protect the tissues from inflammation, oedema and dysfunction.
Neutrophil and macrophage apoptosis is diminished and the lifespan of the phagocytes is extended by ascorbate down regulating neutrophils necrosis and NETosis. (8) This also reduces micro-coagulations at the infection site, (otherwise induced by excessive release of neutrophil or macrophage DNA during apoptosis i.e. NETosis).
In short ascorbate supports phagocytic function during the oxidative battle stage, and this is well before there are any antibodies produced by B and T cells i.e. if the microbe is a new presentation. At this time the gut will absorb much more vitamin C than usual, without causing diarrhoea. Commonly little more than 200mg of ascorbate can be absorbed from an oral dose, but during viral or bacterial infections the absorption can rise to several gram doses at a time.
Does Vitamin C Shorten Acute Infections?
Vitamin C’s efficacy in cold prevention has been extensively studied (9) with two controlled trials finding a dose dependant statistically significant response for the duration of common cold symptoms with up to 6-8g/day of Vitamin C. (10) This dose dependant response of up to 8g/day per day was also considered of greater benefit than lower doses when it came to influencing acute symptoms of the common cold. (11) The effect of adequate doses of vitamin C during a viral infection significantly reduces the secondary bacterial infection that follows in some 45% of URTI’s and otitis.
It is considered that this dose dependency might go some way to explain why some of the trials in vitamin C have not demonstrated benefit. In fact, an early metanalysis of dose dependency calculated this more specifically with 1g/day on average shortened cold duration in adults by 6% and in children by 17%; and equal to or greater than 2g/day of vitamin C shortening the duration of colds in adults by 21% and in children by 26%. (12)
Five controlled trials found significant effects of vitamin C against pneumonia, as an indication of its adjunctive support during non-viral infections. (13)
Overall ascorbate at high doses such as 4 grams a day is especially helpful to innate immunity during the first week of infections. A formula with the added antioxidants assists the functional level of ascorbate to last longer.
At INL we recommend use of Vitamin C as a supplement during the initial stages of infections, particularly the first week, and also for chronic viral infections such as EBV. The rationale is to protect the immune system and other tissues from reactive oxygen species produced during infections, as well as having activating effects for a wide variety of immune functions as outlined.
Orthoplex Clinical C
Orthoplex White Clinical C provides targeted, specialised nutrients to regenerate Vitamin C and provide longer lasting therapeutic benefits. The cofactor in this formula assist antioxidants levels and are designed to recycle vitamin C,E, Q10 and glutathione (View Product).
The optimal doses of vitamin C recommended by INL during acute infections is 1 gram 4 times daily