**5. Discussion and conclusion**

Most interventional studies involving vitamin C supplementation show no benefit irrespective of the dosage, but deficient plasma levels are associated with adverse clinical outcomes [5]. This entails that vitamin C supplementation may only produce a significant effect when there is a deficiency. As demonstrated by Granger

and Eck [5], a peak plasma concentration (plateau) is reached in a deficient individual who is taking vitamin C up to 200–400 mg/day [26].

Due to the wide safety margin of vitamin C and the rapid urinary clearance above the saturation level, most countries and organizations have set the upper level of intake to be 1000–2000 mg/day [6, 8], beyond which the risk of adverse side effects such as gastrointestinal disturbances is increased. Despite the wide margin of safety, doses above 500 mg/day might increase the likelihood of urinary stones in patients prone to urolithiasis [76].

It is important to note that most of the interventional studies considered here were not on vitamin C supplementation alone but on a combination of several vitamins especially vitamins C and E. However, the two vitamins can interact in a synergistic manner [77, 78] to potentiate their effects [79] at different dosages. In addition, some of the estimated doses of vitamin C were from self-reported dietary questionnaires, which might not be accurate.

Sequeira [80] has reported high doses (≥500 mg/kg) of vitamin C, in a review, to cause increase para-cellular transport of drugs, nutrients, and substances not readily absorbed by the intestines probably via some poorly understood mechanisms. However, a possible mechanism could be alteration in the architecture of the tight junctions and the constituted proteins. This could enhance the para-cellular transport of some molecules of interest.

In conclusion, vitamin C dosage recommended in health is dependent on a number of factors such as age, gender, body built, smoking status, pregnancy and lactation, and so on. In disease conditions, the dosage is determined by the type and severity of the disease based on the need to replenish the depleted or deficient levels. In general, taking vitamin C supplement doses higher than the recommended doses is highly encouraged due to the continuous metabolic turnover.
