Vitamin C

What is vitamin C good for?

Vitamin C (L-ascorbic acid) is a water-soluble vitamin. Unlike most animals, humans cannot produce it in the body; therefore it must be obtained from food. According to the NIH, it is required for the synthesis of collagen, L-carnitine and some neurotransmitters and also takes part in protein metabolism. Collagen is the basic component of connective tissue and has an important place in wound healing. ^[1]

Vitamin C is also a physiological antioxidant; it has been shown to regenerate other antioxidants such as vitamin E in the body. It also has a role in immune function and increases the absorption of non-heme iron in plant foods. ^[1] Each of these is “role in the body” information. The existence of a role does not mean that a person with adequate levels needs additional supplements to perform that role better; the sections below address this distinction topic by topic.

How much is the daily requirement?

Reference values vary by body and the criterion used.

The NIH reports that the RDA values are based on the known physiological and antioxidant functions of vitamin C, particularly the level in white blood cells, and are much higher than the amount needed to prevent scurvy. EFSA, on the other hand, found data on health outcomes (such as cancer, cardiovascular disease) insufficient for setting values and based its values on maintaining the body pool. ^{[1] [2]} For pregnancy and lactation, EFSA adds 60 mg per day to the PRI for lactating women and 10 mg for pregnant women. ^[2]

These reference intakes are not “treatment” or “target for immunity” amounts. They are planning values set to meet the needs of healthy people.

How much vitamin C can the body use?

Plasma vitamin C level does not rise proportionally as intake increases. According to the NIH, absorption is about 70–90% at moderate intakes such as 30–180 mg per day and falls below 50% above 1 g per day, and absorbed, unmetabolized ascorbic acid is excreted in urine. Oral 1.25 g/day of ascorbic acid raised the mean peak plasma level to 135 µmol/L; this is about twice what is seen with 200–300 mg per day from food. Modeling predicts that even very high oral doses such as 3 g every 4 hours would give a peak level of only about 220 µmol/L. ^[1]

The practical consequence of this “saturation” behavior is two-sided. First, in a person whose intake is already adequate, additional supplementation is expected to raise blood level only limitedly. Second, as the NIH notes, baseline level was not measured in many observational and intervention studies; if people are already close to saturation, supplementation is not expected to make a difference in outcomes. Therefore, “no benefit shown” results do not mean there is no benefit in people with deficiency or marginal insufficiency. ^[1]

Intravenous (IV) administration exceeds this limit: the NIH reports that while oral doses reach at most about 220 µmol/L, much higher levels can be reached with IV administration. IV use is therefore a different subject from oral supplements and is still being researched in areas such as oncology. ^[1]

What are vitamin C deficiency and scurvy?

Overt vitamin C deficiency leads to scurvy. According to the NIH, signs and symptoms of scurvy can begin within a month of intake below about 10 mg per day; the rate depends on body stores. The first symptoms are fatigue (attributed to impaired carnitine synthesis), malaise and gum inflammation. As deficiency progresses, collagen synthesis is impaired; small bleeding spots in the skin (petechiae), bruising, joint pain, delayed wound healing, skin thickening and curled (corkscrew) hairs are seen. Gum swelling and bleeding, loosening of teeth, depression and iron-deficiency anemia due to bleeding may also accompany it. Untreated scurvy is fatal. ^[1]

Although rare in developed countries, it can be seen in people with limited food variety. Risk groups described by the NIH include smokers and passive smokers, infants fed evaporated or boiled cow’s milk, people with limited food variety, people with severe intestinal malabsorption, some cancer patients and end-stage kidney disease patients on chronic hemodialysis. ^[1]

Plasma vitamin C level is the most commonly used measurement for assessing status; the NIH states that leukocyte level may better reflect tissue level but that it is difficult to measure and results are not always reliable. ^[1]

Does vitamin C help with colds?

The evidence on this question has been examined separately as prevention, duration and use after illness begins. The 2013 Cochrane review examined placebo-controlled trials in which at least 0.2 g of vitamin C per day was used. ^[4]

• Prevention, general population: In general population trials (10,708 participants), regular vitamin C did not significantly change the risk of having a cold (RR 0.97; 95% CI 0.94–1.00). ^[4]
• Prevention, extreme physical stress: In marathon runners, skiers and soldiers on subarctic exercises (five trials, 598 people in total), a pooled RR of 0.48 (95% CI 0.35–0.64) was found. This rests on few and small trials; the result cannot be generalized beyond these special groups. ^[4]
• Duration and severity, with regular use: Duration was shortened by 8% (95% CI 3–12%) in adults and 14% (7–21%) in children; in trials using 1–2 g per day in children, the shortening was reported as 18%. Severity was also reported to be reduced. ^[4]
• After illness begins: In seven comparisons (3,249 illness episodes), no consistent effect on duration or severity was seen. ^[4]

The Cochrane authors conclude that routine vitamin C supplementation in the general population is not justified, but may be useful in those exposed to brief periods of severe physical exercise. The NIH summarizes the same point and states that regular intake of at least 200 mg/day did not reduce cold frequency in the general population and may help in those exposed to extreme exercise or cold and those with marginal vitamin C status. ^{[4] [1]}

Is vitamin C beneficial for skin and collagen?

Vitamin C is indispensable for collagen synthesis; this is well documented as a “role in the body” and is the reason connective tissue weakens in scurvy. ^[1] The review on skin by Pullar and colleagues reports that collagen synthesis by skin fibroblasts is absolutely dependent on vitamin C, as shown in cell cultures and animal studies. ^[7]

The same review emphasizes three points: vitamin C applied to the skin has difficulty reaching the inside of the skin, and most of the formulas that appear most effective in human studies contain vitamins C and E together and a carrier system; an association has been found between adequate fruit and vegetable intake and skin health, but the responsible component is unknown and the effect of vitamin C alone cannot be separated; the benefit of providing vitamin C to the skin in wound healing has been shown in animal and human studies. The review also says that a number of studies reported that signs of aging were reduced, but that measuring skin changes is difficult. The authors state that the efficacy of vitamin C applied to the skin is poorly understood compared with improving dietary vitamin C intake. ^[7] The review was partly funded by a kiwifruit company; the authors report that the funder did not influence the selection of material or its interpretation.

In summary, vitamin C being necessary for collagen and additional oral supplementation changing the skin in a person with adequate levels are different claims: the first is established knowledge, and for the second the cited review offers no conclusive result. In deficiency, however, skin and wound healing are impaired.

Is there evidence for cancer and cardiovascular diseases?

In these two areas, observational data and intervention trials have given results in different directions. The NIH reports that in case-control studies high dietary vitamin C intake was associated with lower risk of some cancers, but that prospective cohort results are inconsistent and that in most randomized trials vitamin C supplementation (alone or with other nutrients) did not affect cancer risk. For example, in the Physicians’ Health Study II, when 500 mg per day of vitamin C plus vitamin E was continued for a mean of 8 years, prostate or total cancer risk was not reduced; in the Women’s Antioxidant Cardiovascular Study, 500 mg per day of vitamin C did not affect total cancer incidence or cancer-related death after a mean of 9.4 years. ^[1]

In cardiovascular disease the picture is similar. According to the NIH, prospective studies are contradictory and most intervention trials have not shown primary or secondary protection from vitamin C supplementation; in the Women’s Antioxidant Cardiovascular Study, 500 mg per day of vitamin C did not reduce events in 8,171 women with a history of cardiovascular disease. In the Women’s Angiographic Vitamin and Estrogen trial (423 postmenopausal women), 500 mg of vitamin C twice daily plus 400 IU of vitamin E provided no cardiovascular benefit and significantly increased all-cause mortality. ^[1]

The NIH also writes that baseline vitamin C level was not measured in many studies and that if people are already close to saturation, no difference is expected from supplementation. Therefore these results do not show that additional intake is useless at inadequate vitamin C levels; what has not been shown is protection in healthy, well-nourished people.

When and how is vitamin C taken?

There is a difference between intake from food and from supplements. The NIH reports that the bioavailability of ascorbic acid in supplements is equivalent to that of ascorbic acid in foods; other forms such as sodium ascorbate and calcium ascorbate, and combination products such as products with bioflavonoids or proprietary products combining calcium ascorbate with ascorbate metabolites, also exist. In one of the small human studies cited by the NIH, such a combination product and ascorbic acid gave the same plasma level while the combination product provided a higher level in leukocytes after 24 hours; in another study no difference was found among the three sources in plasma level or urinary excretion. ^[1]

Because absorption falls as the dose rises and the excess is excreted in urine, it is known that taking a large amount at one time does not raise the blood level proportionally. Details such as time of day and taking with meals are covered on a separate page. This guide does not set personal doses.

Is too much harmful? Kidney stones, iron and drug interactions

The NIH reports that vitamin C has low toxicity and that high intake does not cause serious side effects; the most common complaints are diarrhea, nausea and abdominal cramps due to the osmotic effect of unabsorbed vitamin C in the intestine. The UL for adults is 2,000 mg per day for total intake from food and supplements; 1,800 mg for ages 14–18 and 1,200 mg for ages 9–13. The UL does not apply to people taking vitamin C for medical treatment under physician supervision. ^[1]

Kidney stones. In a prospective cohort study in Swedish men (Thomas et al.; in a cohort of 48,850 men aged 45–79, 23,355 men who used no supplements at all or used only vitamin C were compared, with 436 first stone cases in 11 years of follow-up), ascorbic acid use was associated with an approximately twofold increased stone risk; RR was 2.23 (95% CI 1.28–3.88) in those using 7 or more tablets per week and 1.66 (0.99–2.79) in those using fewer. The authors assume the tablets generally contained about 1,000 mg; the dose was not measured individually. The study covers only men, gives no information on vitamin C from food, and because it is observational, confounders cannot be entirely excluded. ^[5] In the analysis by Ferraro and colleagues (156,735 women in the Nurses’ Health Study I-II, 40,536 men in the Health Professionals Follow-up Study, median follow-up 11.3–11.7 years, 6,245 stones), total vitamin C intake was not significantly associated in women, while in men ≥1,000 mg per day had an HR of 1.43 (1.15–1.79) compared with <90 mg; vitamin C from food was not associated. The data are based on food frequency questionnaires. ^[6] The NIH states that studies on urinary oxalate are contradictory and that the strongest evidence is in people who already have hyperoxaluria. ^[1]

Iron. The NIH reports that vitamin C increasing iron absorption is not a problem in healthy people, but that in people with hereditary hemochromatosis, long-term high doses can worsen iron accumulation. ^[1]

High-dose intravenous. The National Cancer Institute (NCI) patient information text states that IV vitamin C can cause serious side effects in people with kidney disease, G6PD deficiency or hemochromatosis, and that hemolysis has been seen in case reports in G6PD deficiency. ^[8]

Medicines. The NIH reports that the safety and efficacy of antioxidant supplements during chemotherapy and radiotherapy are controversial: some data suggest antioxidants may have protected tumor cells, other data suggest they protect normal tissues or increase the effectiveness of treatment; it is also stated that some data have been criticized for design weakness. In the statin-niacin combination, vitamin C together with other antioxidants has been reported to reduce the HDL increase. ^[1]

Common misunderstandings about vitamin C

• “Vitamin C strengthens immunity, the more I take the better.” Vitamin C plays a role in the function of immune cells, but regular supplementation in the general population did not reduce cold risk; moreover, blood level does not rise proportionally as intake rises. ^{[4] [1]}
• “The excess is excreted in urine anyway, so there is no harm.” The excess amount is largely excreted, but digestive complaints and, in observational studies, stone risk in men are on the agenda. ^{[1] [6]}
• “Vitamin C replaces a collagen supplement.” Vitamin C is a cofactor of collagen synthesis; a collagen supplement is a separate product and vitamin C itself does not contain collagen. ^[1]
• “If I take a high dose once illness starts, it will be shorter.” In vitamin C started after illness began, Cochrane saw no consistent effect. ^[4]

Summary of the evidence

This guide does not recommend personal doses. If there is high-dose supplement use, a history of kidney stones or iron overload, cancer treatment or regular medication use, the decision is made together with a health professional.