Vitamin C — Benefits, Sources, Deficiency, and Daily Dosage

Cardiovascular Health

Increased intake of fruits and vegetables might reduce the risk of heart disease due to their components with antioxidant properties. Vitamin C has been shown to decrease inflammatory changes in blood vessels, improve nitric oxide production, and widen blood vessels, preventing plaque instability in atherosclerosis (1, 8). 

However, the results of prospective studies are conflicting. For example, according to the 16-year prospective Nurses’ Health Study, over 85,000 female nurses who took dietary and supplemental vitamin C had a decreased risk of coronary heart disease, while those consuming only dietary vitamin C showed no significant associations. Furthermore, a smaller study of postmenopausal diabetic women taking 300mg of vitamin C supplements daily had an increased risk of heart disease mortality.

A prospective study of over 20,600 British adults showed that those with higher levels of vitamin C in the plasma had a 42% lower risk of stroke than those with lower levels.

A pooled analysis of several studies, including over 293,000 participants without cardiovascular disease, found that ≥700mg of daily vitamin C supplements decreased the risk of coronary heart disease by 25%. Nonetheless, a 2008 meta-analysis of ten years found that only dietary vitamin C is associated with a decreased risk of heart disease.

Most clinical intervention trials show that vitamin C supplementation might not affect heart disease risk (1, 9, 10). For example, in one study, over 8,000 women aged 40 or above with a history of heart disease were supplemented with 500mg of vitamin C daily for 9.4 years but showed no overall effect on heart events (1).

Low vitamin C intake might be inversely associated with systolic and diastolic blood pressures, noting that people with high blood pressure might have low serum vitamin C levels and benefit from supplementation (10).

Cancer

Increased intake of fruits and vegetables is associated with a decreased risk of most cancer types (such as lung, breast, colorectal, prostate, stomach, esophageal, bladder, cervical, and endometrial cancers), partly due to their high vitamin C levels. In vivo, vitamin C has been shown to limit the formation of carcinogens due to its attenuated oxidative damage to the tissues, a risk factor for cancer (1, 11, 12).

However, the results are inconsistent. In a cohort of over 82,000 women of premenopausal ages, an intake of 205mg of dietary vitamin C daily was associated with a significantly lower risk of breast cancer among women with a family history of cancer. In contrast, many other studies find no strong associations between vitamin C intake and cancer risk.

One study, which included 13,000 healthy French adults who received antioxidant supplements with vitamin C, vitamin E, beta-carotene, selenium, and zinc for 7.5 years, demonstrated a decreased incidence of total cancer in men but not women.

Vitamin C supplements alone or with other antioxidants showed no significant associations between prostate or total cancer risk in the Physicians’ Health Study II and the risk of esophageal or stomach cancers in a large intervention trial conducted in Linxian, China (1).

Oral administration of vitamin C can raise plasma levels to a maximum of 220micromol/L, whereas IV administration can increase them to 26,000micromol/L. This may be selectively toxic or harmful to tumor cells in vitro. However, further research is required to confirm the role of high-dose IV vitamin C as an anti-cancer drug (1).

People on chemotherapy treatment should avoid the intake of antioxidants, such as vitamin A, vitamin C, vitamin E, carotenoids, and coenzyme Q10, as they were reported to increase the risk of disease recurrence by 41% if the supplements were used before and during chemotherapy (13).

Eye Disease

Oxidative stress may be involved in the pathogenesis of two of the most common eye disorders and reasons for vision loss in the elderly—age-related macular degeneration (AMD) and cataracts. Thus, according to a hypothesis, vitamin C and other antioxidants may affect the development or treatment of these conditions. However, most prospective studies could not find direct associations between antioxidant intake and the prevention of early AMD, only suggesting it might help slow disease progression (1).

The AREDS trial evaluated the effect of several antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper) on the development of advanced AMD in nearly 3,600 older adults for 6.3 years. Those at high risk of developing advanced AMD had a 28% lower risk of disease progression. A follow-up AREDS2 trial follow-up for 5 years confirmed the results.

A cohort study of over 30,000 Japanese individuals aged 45-65 linked higher dietary vitamin C intake with a reduced risk of developing cataracts. According to 2 case-control studies, vitamin C intake of >300mg/day may reduce the risk of cataract formation by 70-75%. Another study also noted that vitamin C supplements may delay the onset of cataracts after vitrectomy, occurring in up to 80% of people within 2 years (14). On the other hand, a cohort study of 24,500 Swedish women ages 49-83 noted that high-dose, but not lose-dose, vitamin C supplementation (1g daily) was associated with a 25% increased disease risk (1).

In the AREDS trials, those receiving supplements of 500mg of vitamin C, 400IU vitamin E, and 15mg of beta-carotene did not have a reduced risk of cataract development or progression. The AREDS2 trial confirmed these results (1).

Gout

Gout is arthritis that results from prolonged hyperuricemia (elevated serum uric acid levels), which leads to monosodium urate crystal deposition in the joints and soft tissues. Most epidemiological studies noted a correlation between increased vitamin C intake and lower uric acid levels in the blood (15, 16).

High levels of vitamin C positively affect purine metabolism and reduce serum uric acid levels, thus potentially reducing the risk of crystal deposition in joint structures and soft tissues. However, there is little evidence of vitamin C supplementation in the prevention and treatment of gout or its usefulness during symptom exacerbation. Most studies have short observation periods (15).

Common Cold

For a long time, it has been suggested that vitamin C intake might prevent or treat the common cold.  A 2007 Cochrane review examined several place-controlled trials. It demonstrated that prophylactic use of vitamin C did not significantly reduce the risk of the common cold in the general population but reduced cold incidence by 50% in marathon runners, skiers, and soldiers exposed to extreme physical exercise or cold environments (1).

Vitamin C intake after the onset of symptoms might slightly decrease the duration and severity of the common cold in some. However, a review of 29 trials failed to confirm that vitamin C intake shortened illness duration or the incidence (1, 17, 18, 19).

Vitamin C supplementation may also benefit older adults and chronic smokers (1).

Scurvy

Severe vitamin C deficiency causes scurvy, usually manifesting within a month of <10mg daily vitamin C intake. Low plasma vitamin C levels of <0.2mg/dL and 0mg/dL in leukocytes indicate scurvy, whereas >15mg/dL is sufficient (1, 20).

The first signs include inflammation of the gums, which leads to swelling, bleeding, and tooth loss, as well as fatigue and malaise. 

After some time, impaired collagen synthesis leads to connective tissue weakness, causing petechiae (bleeding spots under the skin and mucose), bruises, purpura (purple patches on the skin or mucosa), joint pain, poor wound healing, hyperkeratosis (skin thickening), corkscrew hairs, and swelling of lower extremities (1, 3, 20).

Iron deficiency or microcytic anemia may also be present, both due to decreased iron absorption and bleeding. Decreased bone mineral density during scurvy may lead to osteopenia, osteoporosis, bone resorption, fractures, dislocations, etc (1, 20).