Vitamin C: Benefits, Best Forms, Dosing, and Side Effects

Table of Contents

• Overview
• Forms and Bioavailability
• Evidence for Health Benefits
• Recommended Dosing
• Dietary Sources
• Safety and Side Effects
• Drug Interactions
• References

1. Overview

Vitamin C (L-ascorbic acid) is an essential water-soluble vitamin that humans cannot synthesize endogenously due to a mutation in the gene encoding L-gulonolactone oxidase, which catalyzes the final step in ascorbic acid biosynthesis [1][2]. Most other animals produce vitamin C internally; humans must obtain it entirely from the diet or supplements.

Vitamin C serves several critical physiological functions [1][2][3]:

• Collagen biosynthesis: Vitamin C is required as a cofactor for prolyl and lysyl hydroxylase, enzymes essential for the cross-linking and stabilization of collagen fibers. Collagen is the most abundant protein in the body, providing structural integrity to blood vessel walls, skin, tendons, ligaments, cartilage, and bone. This makes vitamin C particularly important for wound healing and surgical recovery.
• Antioxidant defense: Vitamin C is one of the most potent water-soluble antioxidants in human blood plasma [3]. It scavenges reactive oxygen species (free radicals) and reactive nitrogen species, protecting cells from oxidative damage. Vitamin C also regenerates other antioxidants, including alpha-tocopherol (vitamin E), restoring their antioxidant capacity [4].
• Immune function: Vitamin C accumulates in leukocytes (white blood cells) at concentrations 10- to 100-fold higher than in plasma, supporting both innate and adaptive immunity. It enhances neutrophil chemotaxis, phagocytosis, and microbial killing, and supports lymphocyte proliferation [4].
• Neurotransmitter synthesis: Vitamin C is a cofactor for dopamine beta-hydroxylase, the enzyme that converts dopamine to norepinephrine. It also participates in the synthesis of other neurotransmitters and neuromodulators [1][2].
• L-carnitine synthesis: Vitamin C is required for the biosynthesis of L-carnitine, which is essential for fatty acid transport into mitochondria for energy production [1][2].
• Iron absorption: Vitamin C enhances the absorption of nonheme iron (the form present in plant-based foods) by reducing ferric iron (Fe3+) to ferrous iron (Fe2+) in the gut, making it more bioavailable [5]. However, research suggests that this effect may be clinically modest [6].
• Protein metabolism: Vitamin C is involved in the metabolism of several amino acids and the amidation of peptide hormones [1][2].

Absorption and Pharmacokinetics

The intestinal absorption of vitamin C is regulated by at least one specific dose-dependent, active transporter — the sodium-dependent vitamin C transporter (SVCT1) [4]. Absorption efficiency is approximately 70-90% at moderate intakes of 30-180 mg/day. However, at doses above 1 g/day, absorption falls to less than 50%, and absorbed, unmetabolized ascorbic acid is excreted in the urine [4][7].

Pharmacokinetic studies show that the relationship between dose and plasma concentration is nonlinear and tightly controlled [4][7]:

• At 200-300 mg/day from vitamin C-rich foods, mean peak plasma concentrations reach approximately 60-70 micromoles/L.
• Oral doses of 1.25 g/day produce mean peak plasma concentrations of approximately 135 micromoles/L — only about twice the level achieved at 200-300 mg/day [7].
• Pharmacokinetic modeling predicts that even 3 g taken every 4 hours would produce peak plasma concentrations of only 220 micromoles/L [7].
• By contrast, intravenous administration can produce plasma concentrations as high as 26,000 micromoles/L — more than 100-fold higher than achievable orally [7][8].

The total body content of vitamin C ranges from approximately 300 mg (at near-scurvy levels) to about 2 g [4]. Cells appear to become saturated at daily intakes of approximately 100 mg, and plasma concentrations plateau at intakes of 200 mg or more [4][7]. The highest concentrations are maintained in leukocytes, adrenal glands, the pituitary gland, the eyes, and the brain [4].

Vitamin C status is typically assessed by measuring plasma vitamin C levels [4][9]. A plasma level below 11.4 micromoles/L (0.2 mg/dL) indicates deficiency (scurvy risk). Levels of 23-49 micromoles/L indicate hypovitaminosis C (suboptimal status). Levels of 50-70 micromoles/L are considered adequate, and levels above 70 micromoles/L indicate saturation. To convert micromoles/L to mg/dL, multiply by 0.0176 (56.82 micromoles/L = 1 mg/dL) [6].

Deficiency: Scurvy and Beyond

Prolonged vitamin C deficiency causes scurvy, which can appear within 1 month of consuming less than about 10 mg/day [1][10][11]. Symptoms progress from initial fatigue, malaise, and gum inflammation to petechiae (tiny red dots from capillary bleeding), ecchymoses (bruises), purpura, joint pain, poor wound healing, hyperkeratosis, and corkscrew hairs [1][2][4][10][11]. If untreated, scurvy is fatal. Children can develop bone disease [10]. Iron deficiency anemia may co-occur due to increased bleeding and decreased nonheme iron absorption [10][12].

Scurvy is rare in developed countries today, but several populations remain at risk [6][10]:

• People with alcohol use disorder
• Smokers (who have increased oxidative stress depleting vitamin C stores)
• Long-term users of proton pump inhibitors
• Those with highly restrictive or poor-quality diets
• Patients who have undergone bariatric surgery without adequate nutritional follow-up (a case report described a man in Australia diagnosed with scurvy and undetectable vitamin C levels eight years after gastric sleeve surgery; his condition improved with 1,000 mg/day vitamin C plus a multivitamin and nutritional counseling [6])
• People with severe intestinal malabsorption or cachexia
• Patients with end-stage renal disease on chronic hemodialysis [13]

Even subclinical vitamin C insufficiency has clinical consequences. A review of 15 clinical trials concluded that in people with plasma vitamin C levels of 27 micromoles/L or below, vitamin C supplementation (average dose 222 mg for 41 days) reduces gingival (gum) bleeding. The researchers suggested that about 110 mg daily would be sufficient for this purpose — more than the current RDAs for most adults. In those with normal plasma levels (48-70 micromoles/L), supplementation did not reduce gum bleeding [14].

Vitamin C deficiency can also mimic inflammatory conditions such as juvenile arthritis. A report described 10 patients aged 3 to 20 with restrictive eating habits who presented with muscle and joint pain initially thought to be rheumatic disease but were ultimately found to have low vitamin C levels. Supplementation at 250-1,000 mg/day resolved symptoms in all patients [15].

Additionally, severe vitamin C deficiency has been implicated in cases of pulmonary arterial hypertension (PAH) through impaired endothelial function, generally with co-occurring iron deficiency. A man in his 60s with severe deficiency due to poor diet presented with shortness of breath, leg swelling, and other deficiency symptoms. After 5 months of treatment with 1,000 mg vitamin C twice daily, his symptoms resolved and his plasma levels rose from 5.7 micromoles/L (near undetectable) to 85 micromoles/L [16].

2. Forms and Bioavailability

Vitamin C supplements are available in several chemical forms. The key differences between forms relate to acidity and gastrointestinal tolerance rather than to major differences in bioavailability, as most forms provide comparable absorption of vitamin C [9][17][18].

Comparison Table

Form	Description	Bioavailability	GI Tolerance	Key Notes
Ascorbic acid	Standard form; the chemical name for vitamin C. Both natural and synthetic forms are the same "L" isomer and are equally used by the body [6][17].	Reference standard (~70-90% at moderate doses)	Acidic; may cause heartburn or stomach upset at high doses	Lowest cost. No reason to pay more for "natural" or "fully reduced" products, as properly manufactured vitamin C is already in a fully reduced state [6].
Calcium ascorbate (Ester-C)	Non-acidic form; vitamin C combined with calcium. A patented form that also contains metabolites (dehydroascorbate, calcium threonate, xylonate, lyxonate) [18].	Plasma absorption similar to ascorbic acid; one sponsored study found leukocyte levels remained elevated for 24 hours [19].	Better for acid-sensitive stomachs; non-acidic	Does not reduce diarrhea risk (which is unrelated to acidity). The claim of superior absorption is not supported by reliable independent evidence [6][18].
Sodium ascorbate	Non-acidic form; vitamin C combined with sodium. Sometimes marketed as "buffered vitamin C" when combined with ascorbic acid.	Similar to ascorbic acid [17][18]	Non-acidic; gentler on the stomach	Contains sodium — may be a concern for those restricting sodium intake [6].
Ascorbyl palmitate	Fat-soluble form; often found in softgel capsules.	Mixed evidence; may improve absorption slightly but not clearly demonstrated [6].	Good	Useful for oil-based formulations.
Liposomal vitamin C	Vitamin C encapsulated in a phospholipid (fat) layer, designed to enhance absorption through cell membranes.	One manufacturer-conducted study found a single 500 mg dose increased blood levels 21% more than non-liposomal vitamin C and 8% more in white blood cells [20]. However, an earlier study at 5 g found no advantage [21].	Good	Significantly more expensive (~50 cents per 500 mg vs. a few cents for regular ascorbic acid). The modest absorption advantage does not justify the cost premium for most people [6].
Liposomal hydrogel vitamin C	Liposomal vitamin C encased in a hydrogel matrix (e.g., galactomannan from fenugreek seed).	One manufacturer-conducted study found blood levels nearly 7 times higher over 12 hours compared to unformulated vitamin C from a 1,000 mg tablet providing ~350 mg vitamin C [22].	Good	Expensive (~33 cents per 500 mg). Study did not evaluate performance when taken with food.
PureWay-C (ascorbic acid + fatty acids)	Vitamin C combined with lipid metabolites.	After 4 hours, absorption from a 1 g dose was similar to ascorbic acid and Ester-C [23].	Good	No demonstrated absorption advantage over regular ascorbic acid.

Key Principles for Form Selection

For most people: Regular ascorbic acid is the preferred form due to its equivalent bioavailability and significantly lower cost. A comprehensive comparison study found no differences in plasma vitamin C levels or urinary excretion among ascorbic acid, Ester-C, and ascorbic acid with bioflavonoids, leading the authors to conclude that simple ascorbic acid is the preferred source of supplemental vitamin C [18].

For those with sensitive stomachs: Calcium ascorbate (Ester-C) or sodium ascorbate are non-acidic alternatives that avoid the heartburn or gastric irritation that ascorbic acid can cause at higher doses. Note that diarrhea from high-dose vitamin C is caused by osmotic effects of unabsorbed vitamin C in the gut, not by acidity, so non-acidic forms do not prevent this side effect [6].

For maximizing absorption at high doses: Pharmacokinetic data show that absorption of vitamin C decreases at higher single doses. The most effective strategy for maintaining higher blood levels is to divide the dose into several smaller portions throughout the day (e.g., 250-500 mg two to three times daily), rather than taking a single large dose [24]. Slow-release formulations may also help by providing more gradual delivery [24].

Regarding "natural" vitamin C sources: Rose hips powder is only about 2% vitamin C, so 500 mg of rose hips powder contributes only 10 mg of vitamin C. Products containing 10-20 mg of rose hips — an amount commonly listed on vitamin C supplement labels — provide less than 1 mg of vitamin C from this source, essentially a marketing ingredient. Acerola powder is approximately 1.5% vitamin C. Camu camu dried pulp powder is about 13-15% vitamin C, and extract may be up to 20%. All natural sources provide the same L-ascorbic acid that synthetic production yields [6].

Regarding bioflavonoids: Some vitamin C supplements include citrus bioflavonoids (hesperidin, quercetin, rutin) based on a small 1988 study suggesting they increased vitamin C bioavailability by 35% [25]. These results have not been reliably replicated. Most products provide far less bioflavonoid per serving than the typical clinical dosage of 500 mg twice daily. Bioflavonoids may have independent therapeutic value (e.g., for hemorrhoids, venous insufficiency, leg ulcers), but they have not been conclusively shown to enhance vitamin C absorption in the body [6].

Topical Vitamin C for Skin

Vitamin C is naturally present in the skin and plays a role in collagen synthesis and may help protect skin against environmental stress due to its antioxidant effects [26]. Research has found lower vitamin C levels in aged or sun-damaged skin [27], generating interest in topical application.

However, the evidence for topical vitamin C is limited:

• Vitamin C cannot easily penetrate the outermost skin layer (stratum corneum). Applying vitamin C topically does not boost skin levels if the blood is already saturated, which occurs with daily oral intake of approximately 500 mg [28][29].
• Laboratory research on animal skin found that best absorption required a pH below 3.5 and vitamin C concentrations of 10-20% [28]. Products containing vitamin E and ferulic acid may help increase formulation stability [30][31].
• A small study of women (average age 55) with photo-aged skin found that applying 5% vitamin C serum daily for 6 months improved investigator-rated skin properties by only 2.3 points on a 17-point scale versus 1.4 points with placebo [32].
• Several studies showed that sunscreen containing vitamin C combined with vitamin E reduced UV-induced skin damage more than sunscreen alone [33][34][35]. However, applying 5% vitamin C alone did not prevent UV-induced skin redness compared to placebo [36].
• Phosphate derivatives are more stable but less well absorbed. Palmitate derivatives may improve absorption but evidence is mixed. Glucoside derivatives show greater stability and penetration, but it is unknown whether this form converts to active ascorbic acid after skin penetration. Dehydroascorbic acid does not appear to increase skin vitamin C levels when applied topically [28][26].

Dr Brad Stanfield's MicroVitamin includes 45 mg of vitamin C as calcium ascorbate — a non-acidic form chosen for gentle absorption alongside the other 24 ingredients in the daily serving (shop MicroVitamin).

3. Evidence for Health Benefits

Common Colds and Immune Function

The relationship between vitamin C and the common cold has been studied extensively since Linus Pauling's 1970 proposal that high-dose vitamin C could prevent and treat colds [37].

Prevention (prophylactic use): A Cochrane meta-analysis of 44 placebo-controlled studies examined vitamin C at doses of at least 200 mg/day taken continuously [38]:

• General population: Prophylactic vitamin C did NOT significantly reduce the risk of developing a cold.
• People under severe physical stress: In trials involving marathon runners, skiers, and soldiers exposed to extreme physical exercise and/or cold environments, prophylactic vitamin C (250 mg/day to 1 g/day) reduced cold incidence by 50%.
• Duration and severity: In the general population, regular prophylactic vitamin C modestly reduced cold duration by 8% in adults and 14% in children. Cold symptoms were slightly less severe (by 5% in one large study).

A small study of men aged 18-35 with low to adequate vitamin C levels found that 1 g/day (500 mg twice daily) for 2 months during winter reduced reported colds compared to placebo (7 vs. 11 colds) [39].

Treatment (after symptom onset): Studies evaluating vitamin C supplementation started after cold symptoms develop have not conclusively shown a benefit [38]. A 2018 analysis (Ran, Biomed Res Int 2018) claimed that high-dose vitamin C might shorten cold duration in regular supplementers, but this review was retracted in 2023 due to calculation errors [40].

Practical recommendation: For cold prevention, regular daily supplementation of 200 mg to 1 g may modestly reduce cold duration and severity, particularly in those with suboptimal vitamin C status, people exposed to extreme physical stress, smokers, and older adults [38][41][42]. Starting vitamin C after symptoms have already begun does not appear helpful. The modest antihistamine effect of high-dose vitamin C may contribute to symptom amelioration [43].

COVID-19

Vitamin C's role in immune function led to widespread promotion for COVID-19 prevention and treatment. However, clinical evidence has been largely negative:

• A study of 214 adults with COVID-19 found that 8,000 mg/day of vitamin C did not significantly decrease symptom duration compared to standard care. Those taking vitamin C were more likely to experience nausea, diarrhea, and stomach cramps. Combining vitamin C with high-dose zinc (50 mg/day) also showed no benefit [44].
• A study of 98 adults aged 40+ with mild to moderate COVID-19 found that 1,000 mg/day of vitamin C for 14 days did not reduce symptom number, duration, severity, or quality of life versus placebo [45].
• Two large studies of hospitalized COVID-19 patients found that high-dose intravenous vitamin C (approximately 4,000 mg every 6 hours for 4 days) did not increase days off life-support equipment. Critically ill patients on IV vitamin C required more days on life support and were slightly less likely to survive to discharge, suggesting harm rather than benefit [46].
• A trial of 56 patients in China with severe SARS-CoV-2 pneumonia found that extremely high-dose IV vitamin C (24,000 mg/day for 7 days) slightly improved blood oxygenation but did not reduce ventilator-free days or mortality over 28 days [47].
• A retrospective study of 15 critically ill COVID-19 patients in shock found 80% mortality despite treatment with 3,000 mg/day vitamin C [48].
• A review of pre-COVID studies found that 1,000-6,000 mg of vitamin C (IV or oral) shortened ventilation time by about 25% for patients requiring ventilation for over 10 hours, but was less helpful for shorter ventilation periods [49].

Very high-dose vitamin C (typically 2,000 mg/day or more) can increase the risk of oxalate nephropathy. Cases of this condition rose during the first two years of the COVID-19 pandemic, likely due to increased use of very high-dose vitamin C [50].

Blood Pressure

Blood pressure appears to be modestly reduced with vitamin C supplementation, at least in short-term studies.

A meta-analysis of 29 short-term studies, most using 500-1,000 mg/day, found average decreases of 3.84 mmHg systolic and 1.48 mmHg diastolic [51]. In patients with hypertension, the reductions were somewhat larger: 4.85 mmHg systolic and 1.67 mmHg diastolic. The blood pressure reduction is minor compared to pharmaceutical treatments (ACE inhibitors and diuretics reduce pressures by approximately 10 mmHg), and the studies were short (2 weeks to 6 months), so effects on cardiovascular events were not assessed [51].

Vitamin C's blood pressure-lowering mechanism may involve reducing endothelin-1 activity, thereby relaxing blood vessels. A 3-month US study found that 500 mg/day of timed-release vitamin C in overweight and obese individuals (who tend to have elevated endothelin-1 activity) reduced endothelin-1 activity as much as daily aerobic walking for 45-60 minutes. Participants were not vitamin C deficient at baseline (mean blood level 68 micromoles/L, rising to 85.2 micromoles/L with supplementation) [52].

Blood Sugar and Type 2 Diabetes

A study of 27 overweight or obese adults with type 2 diabetes showed that 500 mg vitamin C twice daily for 4 months lowered blood pressure by an average 7 mmHg systolic and 5 mmHg diastolic compared to placebo, and reduced postprandial glucose by 36%, with a 2.8-hour reduction in daily elevated glucose duration. There was no significant improvement in HbA1c, possibly due to the limited study size and duration [53].

Cardiovascular Disease

The evidence for vitamin C in cardiovascular disease prevention is mixed, with observational studies suggesting benefit but clinical trials largely negative.

Epidemiological data: High intakes of fruits and vegetables are consistently associated with reduced CVD risk, partly attributed to antioxidant content [1][54][55]. Vitamin C can reduce monocyte adherence to the endothelium, improve nitric oxide production and vasodilation, and reduce vascular smooth muscle cell apoptosis, which helps prevent plaque instability in atherosclerosis [2][56]. Vitamin C may also help maintain the effectiveness of nitrate drugs such as nitroglycerin taken for chest pain and coronary artery disease [6].

Prospective cohort studies provide conflicting results:

• In the Nurses' Health Study (85,118 women, 16-year follow-up), total vitamin C intake from both dietary and supplemental sources was inversely associated with coronary heart disease risk, but dietary vitamin C alone showed no significant association — suggesting that supplement users might be at lower risk [57].
• A study of 20,649 British adults found those in the top quartile of baseline plasma vitamin C had a 42% lower risk of stroke than those in the bottom quartile [58].
• A pooled analysis of 9 prospective studies (293,172 subjects) found that supplemental vitamin C at 700 mg/day or more was associated with a 25% lower risk of coronary heart disease compared to no supplemental vitamin C [59].
• A 2008 meta-analysis of 14 prospective cohort studies (median 10 years follow-up) concluded that dietary, but not supplemental, vitamin C intake was inversely associated with coronary heart disease risk [54].
• In male physicians (Physicians' Health Study), vitamin C supplement use for a mean of 5.5 years was not associated with decreased CVD or coronary heart disease mortality [60].

Clinical trials have been largely negative:

• Women's Antioxidant Cardiovascular Study (8,171 women with CVD history, mean 9.4 years): 500 mg/day vitamin C showed no overall effect on cardiovascular events [61].
• Physicians' Health Study II (male physicians, mean 8 years): 500 mg/day vitamin C had no effect on major cardiovascular events [62].
• SU.VI.MAX study (13,017 French adults, 7.5 years): Combination supplementation (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 mcg selenium, 20 mg zinc) had no effect on ischemic CVD in either men or women [63].
• Women's Angiographic Vitamin and Estrogen study (423 postmenopausal women with coronary stenosis): 500 mg vitamin C plus 400 IU vitamin E twice daily significantly increased all-cause mortality compared to placebo [64].
• A 2006 meta-analysis of RCTs concluded that antioxidant supplements (vitamins C and E, beta-carotene, or selenium) do not affect the progression of atherosclerosis [65].
• However, the Linxian, China population trial found that daily vitamin C (120 mg) plus molybdenum (30 mcg) for 5-6 years significantly reduced cerebrovascular death risk by 8% during 10 years of follow-up after the intervention ended [66].

Mortality data — conflicting findings at higher blood levels:

• A long-term US study (approximately 14-year follow-up) found that death risk was lowest when blood vitamin C levels exceeded the bottom 20% of the population (above 15.33 micromoles/L) and continued to decrease until 45.99-59.62 micromoles/L, with no further decrease beyond this. CVD mortality followed a similar pattern. Cancer mortality continued to decrease even at the highest blood levels (at or above 60.19 micromoles/L) [67].
• However, an observational study of nearly 10,000 US adults (approximately 10-year follow-up) found that blood levels at or above approximately 60 micromoles/L were associated with a 33% greater risk of all-cause mortality and 60% greater risk of CVD mortality compared to lower levels [68]. This level is at the upper end of the adequate range and near saturation.
• One study found that postmenopausal women with diabetes who took at least 300 mg/day of supplemental vitamin C were more likely to die from CVD [69]. No such association has been reported in other studies.

Synthesis: Current evidence does not support vitamin C supplementation specifically for cardiovascular disease prevention. However, maintaining adequate vitamin C status through diet and/or modest supplementation is reasonable given consistent observational associations and known biological mechanisms. A fundamental limitation of the clinical trials is that most participants likely had vitamin C levels near tissue saturation at baseline, so supplementation would have had little additional effect [2][7].

Cancer Prevention

The evidence for vitamin C in cancer prevention is inconsistent and does not support supplementation for this purpose.

Epidemiological data: Most case-control studies have found inverse associations between dietary vitamin C intake and cancers of the lung, breast, colon/rectum, stomach, oral cavity, larynx/pharynx, and esophagus [2][4]. Plasma vitamin C concentrations are also lower in people with cancer than in those without [2].

• In the Nurses' Health Study (82,234 women, ages 33-60), consuming approximately 205 mg/day of vitamin C from food (highest quintile) was associated with a 63% lower risk of breast cancer among premenopausal women with a family history [70].
• However, Kushi and colleagues did not observe significantly lower breast cancer risk among postmenopausal women consuming at least 198 mg/day (highest quintile) versus less than 87 mg/day (lowest quintile) [71].
• A review by Carr and Frei noted that studies reporting no association typically enrolled subjects with relatively high vitamin C intakes (above 86 mg/day in the lowest quintiles), whereas studies finding protective effects identified them at intakes of 80-110 mg/day — a range near tissue saturation [2].

Clinical trials have been negative:

• Physicians' Health Study II: 500 mg/day vitamin C did not reduce the risk of prostate or total cancer in men aged 50+ [72].
• Women's Antioxidant Cardiovascular Study: 500 mg/day vitamin C for 9.4 years had no significant effect on total cancer incidence or cancer mortality [73].
• SU.VI.MAX study (13,017 adults, 7.5 years): Combined antioxidant supplementation (including 120 mg vitamin C) lowered total cancer incidence in men but not in women. Baseline antioxidant status was related to cancer risk in men but not women [63][74].
• Linxian, China: 120 mg vitamin C plus 30 mcg molybdenum for 5-6 years did not significantly affect esophageal or gastric cancer risk. During 10 years of follow-up, this supplementation did not significantly affect total cancer morbidity or mortality [66][75].
• A 2008 Cochrane review found no convincing evidence that vitamin C (or beta-carotene, vitamin A, or vitamin E) prevents gastrointestinal cancers [76].

Prostate cancer: A large study of older men in Canada found no association between vitamin C intake (from food and/or supplements) and subsequent prostate cancer diagnosis or severity [77].

Breast cancer concern: A 10-year observational study of 57,403 women in France found that women with high dietary vitamin C intake (>177.6 mg/day) had reduced postmenopausal breast cancer risk, but women who also took vitamin C supplements on top of high dietary intake had an increased risk [78].

In vitro concern: There is test-tube evidence that vitamin C may cause the production of DNA-damaging genotoxins that promote cancer development, arguing against high-dose vitamin C for cancer prevention [9].

Cancer Treatment

The role of vitamin C in cancer treatment remains controversial and under active investigation.

Historical context: In the 1970s, Cameron, Campbell, and Pauling reported that high-dose vitamin C (intravenous and oral) had beneficial effects on quality of life and survival in terminal cancer patients [79][80]. However, a subsequent randomized, double-blind, placebo-controlled trial at the Mayo Clinic found that 10 g/day oral vitamin C produced no benefit over placebo in advanced colorectal cancer [81]. A 2003 review concluded that vitamin C confers no significant survival benefit in advanced cancer [82].

The IV vs. oral distinction: The discrepancy between the early positive findings and the Mayo Clinic result may be explained by route of administration. Cameron and colleagues used both IV and oral vitamin C, while Moertel's Mayo Clinic trial used only oral. Oral vitamin C can produce plasma concentrations of at most 220 micromoles/L, whereas intravenous administration can achieve 26,000 micromoles/L [7][8]. At these pharmacologic concentrations, vitamin C is selectively cytotoxic to tumor cells in vitro, acting as a pro-oxidant that generates hydrogen peroxide with selective toxicity toward cancer cells [83][84][85]. Based on this rationale, several case reports of remarkably long survival in patients with advanced cancers treated with high-dose IV vitamin C, and promising animal data, some researchers advocate for reassessment of IV vitamin C as a cancer treatment [3][8][86].

Safety concern during treatment: Whether vitamin C (and other antioxidants) interacts with chemotherapy or radiation therapy is unresolved. Some data suggest antioxidants might protect tumor cells from treatment [87][88][89]. Other data suggest they protect normal tissues from treatment-induced damage and/or enhance treatment effectiveness [90][91]. Due to this uncertainty, individuals undergoing chemotherapy or radiation should consult their oncologist before taking vitamin C, especially at high doses [87].

Cataracts and Age-Related Macular Degeneration (AMD)

Cataracts — evidence for moderate-dose benefit, high-dose risk:

• A UK study found that people with the highest dietary vitamin C intakes were 19% less likely to have nuclear cataracts and 33% less likely to experience 10-year cataract progression compared to those with the lowest intakes. Those who had taken supplements (including multivitamins) were also less likely to have cataracts, but this did not reduce subsequent progression risk [92].
• Long-term studies (>10 years) suggest that the daily vitamin C intake needed to saturate the eye is only about 150-250 mg/day and that this modest dose may reduce cataract risk [93].
• A long-term study of a moderate-dose multivitamin (containing 60 mg vitamin C) found reduced cataract risk, but adding a separate high-dose vitamin C supplement (500 mg/day — about 6 times the RDA) eliminated this benefit [93].
• In a 5-year Japanese cohort of more than 30,000 adults aged 45-64, higher dietary vitamin C was associated with reduced cataract risk [94].
• Case-control studies indicate that vitamin C intakes greater than 300 mg/day reduce cataract formation risk by 70-75% [2][4].
• However, an 8-year Swedish study of 25,593 women found a 25% increase in cataract removals among those supplementing with approximately 1,000 mg/day. Women supplementing for 10+ years had a 46% increase [95].
• In the AREDS trial, high-dose supplementation (500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene) did not significantly reduce cataract risk or progression [96]. The AREDS2 study confirmed this [97].

Synthesis for cataracts: Over the long term (10+ years), low-to-moderate-dose vitamin C (60-250 mg/day) appears to help prevent cataracts, while high-dose supplementation (approximately 1,000 mg/day) does not and may increase risk.

Age-Related Macular Degeneration (AMD):

• A 2007 systematic review and meta-analysis concluded that vitamin C and other antioxidants, including supplements, do not play a role in the primary prevention of early AMD [98].
• A population-based cohort study in the Netherlands found that older adults (55+) with high dietary intakes of vitamin C, beta-carotene, zinc, and vitamin E had reduced AMD risk [99], but most other prospective studies have not supported this finding [100].
• However, the AREDS trial (3,597 older adults, average 6.3-year follow-up) found that high-dose antioxidant supplementation (500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene, 80 mg zinc, 2 mg copper) reduced the risk of progressing to advanced AMD by 28% in high-risk individuals (those with intermediate AMD or advanced AMD in one eye) [101]. The AREDS2 study confirmed these findings over a median 5-year follow-up [102].

Note that high-dose vitamin C (452-500 mg/day) is part of the AREDS formula, but its individual contribution cannot be isolated from the multi-nutrient combination. Despite this, the AREDS formula is a standard clinical recommendation for patients at high risk of advanced AMD progression.

Gout and Uric Acid

In men, supplemental vitamin C intake is inversely associated with gout risk. Compared to men who did not supplement with vitamin C, intakes of 1,000-1,499 mg and more than 1,500 mg were associated with 34% and 45% reductions in gout risk, respectively [103]. This may result from lower serum uric acid levels, which decrease with vitamin C intakes up to 400-500 mg/day, with no further reduction at higher doses [104].

A study of 40 healthy men and women (average age 49) without gout history but with upper-normal serum uric acid levels found that a drink containing 592 mg vitamin C daily for one week decreased serum uric acid by 0.48 mg/dL versus a 0.10 mg/dL decrease with control. The difference was statistically significant, with the strongest effect in those with lower baseline vitamin C levels. It is not known whether this would benefit people with elevated uric acid levels or a history of gout [105].

Nonalcoholic Fatty Liver Disease (NAFLD)

Higher dietary vitamin C intake (>146 mg/day) has been associated with 29% lower odds of NAFLD compared to lower intake (<75 mg/day) [106]. A study in China among 84 people with recently diagnosed NAFLD — none of whom were vitamin C deficient — showed that taking 200, 1,000, or 2,000 mg of vitamin C daily before meals for 12 weeks improved markers of liver function (AST, ALT, and/or GGT), with those in the 1,000 mg group consistently showing the greatest benefit. However, the lack of a placebo control group limits validity. None of the three groups showed improvements in total cholesterol, triglycerides, or albumin [107].

Mood and Depressive Symptoms

Vitamin C plays a role in norepinephrine synthesis, depletion of which has been linked with depressive symptoms [108][109]. Observational and interventional data yield mixed results:

• An observational study of 25,895 healthy adults in China (average age 49) found that dietary vitamin C intake above 92.95 mg/day was associated with 27% lower odds of depressive symptoms compared to low intake (<39.55 mg/day). The association was dose-dependent up to 126 mg/day, above which there was no additional benefit. Supplementing with vitamin C was associated with 22% lower risk. The association was significant for women and people aged 19-59, but not for men or people 60+ [110].
• A study of 46 young adults in Korea (not vitamin C deficient) found that 500 mg twice daily for 4 weeks provided no benefit on measures of fatigue, depression, stress, positive and negative affect, or anxiety, though there was a small improvement (1.6 points on a 14-point scale) in attention [111].
• A study of 128 healthy young adults in New Zealand (not vitamin C deficient) found that 250 mg/day for 4 weeks did not improve mood disturbances (depressive symptoms, anxiety, anger), but slightly improved vitality measures (fatigue improved by approximately 3.8 points on a 120-point scale, mental well-being by 1.3 points on a 56-point scale). Similar improvements were seen with two daily kiwifruits providing the same amount of vitamin C. The study was funded by Zespri International Ltd., a kiwifruit marketer [112].

Synthesis: Observational data link adequate vitamin C intake with lower depression risk, but clinical trials have not demonstrated that supplementation improves mood in people who are not vitamin C deficient. Ensuring adequate intake (meeting the RDA) is reasonable, but supplementation beyond this for mood benefits is not supported.

Shingles (Herpes Zoster)

Low blood levels of vitamin C (45 micromoles/L or below) have been associated with increased risk of developing post-herpetic neuralgia — nerve pain persisting after shingles lesions heal [113]. Intravenous vitamin C (2.5-15 g daily or every other day for 3-14 days), alongside standard treatment, has been shown to reduce delayed post-herpetic pain and its severity, but not acute shingles pain [114][115]. No clinical studies have investigated the effects of oral vitamin C supplementation on shingles or post-herpetic neuralgia.

Wound Healing and Foot Ulcers

Vitamin C is essential for collagen synthesis, making it critical for wound healing. A small clinical trial in Australia studied 16 older adults (average age 60) being treated for foot ulcers who had diabetes, vascular disease, neuropathy, or foot deformities. They received 500 mg of vitamin C (slow-release tablet) or placebo (glucosamine) daily for 2 months. Half the patients in each group were vitamin C deficient at baseline. Complete healing occurred in all vitamin C recipients versus only 56% of placebo recipients [116].

Exercise Performance

The relationship between vitamin C supplementation and exercise is complex. High-dose vitamin C may impair training adaptations by blunting the beneficial oxidative stress signals that drive physiological adaptation:

• A 10-week study in healthy young women found that 1,000 mg vitamin C plus 400 IU vitamin E daily prevented increases in fat-free mass (muscle) during strength training, while the placebo group gained muscle and decreased fat mass. The researchers concluded these vitamins "should be avoided by healthy young women who want to increase fat-free mass" [117].
• An 11-week study in Norway found that 500 mg vitamin C with 260 IU synthetic vitamin E (taken before and after training, and morning/evening on rest days) prevented the increase in mitochondrial proteins thought to improve muscular endurance during running and cycling training 3-4 times per week. However, overall performance (VO2max and a running test) improved equally in both groups. A similar study using half the vitamin C dose did not find this blunting effect. The authors advise caution with high-dose antioxidant supplementation during endurance training [118].
• A 12-week study in healthy elderly men found that high-dose vitamin C/E during strength training constrained bone density benefits compared to placebo. Lower back bone density increased more in the placebo group, and hip bone density increased only in the placebo group [119].
• However, a study of 86 young male athletes in India with adequate blood vitamin C/E levels but low dietary intake found that 1,000 mg vitamin C and/or 400 mg vitamin E during 8 weeks of high-intensity interval training (HIIT) did not impair improvements in maximal oxygen consumption or body weight reduction. Those supplementing with vitamin C plus vitamin E showed slightly greater improvement in vertical jump height. The authors suggested vitamin C and E may have reduced HIIT-induced oxidative stress without blunting adaptation in this population [120].

Synthesis: High-dose vitamin C supplementation (500-1,000 mg/day), particularly in combination with vitamin E, may interfere with beneficial exercise adaptations including mitochondrial biogenesis, muscle growth, and bone density improvements in healthy individuals. Athletes and those engaged in regular training should be cautious about high-dose antioxidant supplementation during training periods.

Nail Health

Vitamin C deficiency has been associated with nail changes including koilonychia (spoon nails) and hapalonychia (soft, thin nails that bend or break) [121]. However, no clinical studies demonstrate that vitamin C improves nail health or strength in people who are not deficient in vitamin C or iron [122].

Nickel Sensitivity

Some research has shown that vitamin C can reduce the absorption of nickel, which may theoretically benefit people with nickel sensitivity, although no clinical research has demonstrated that vitamin C reduces eczema symptoms in nickel-sensitive individuals [6].

4. Recommended Dosing

Recommended Dietary Allowances (RDAs)

From the National Academies Food and Nutrition Board [9][12]:

Age Group	Male (mg/day)	Female (mg/day)	Pregnancy	Lactation
0-6 months	40*	40*	--	--
7-12 months	50*	50*	--	--
1-3 years	15	15	--	--
4-8 years	25	25	--	--
9-13 years	45	45	--	--
14-18 years	75	65	80	115
19+ years	90	75	85	120
Smokers	+35	+35	--	--

* Adequate Intake (AI)

People who smoke require an additional 35 mg/day due to increased oxidative stress and lower plasma vitamin C levels [9][12]. Exposure to secondhand smoke also decreases vitamin C levels, though a specific additional requirement has not been established [12].

The RDAs are based on the known physiological and antioxidant functions of vitamin C in white blood cells and are much higher than the amount required for protection from deficiency (approximately 10 mg/day) [4][9][12].

Tolerable Upper Intake Level (UL)

The UL for vitamin C from food, beverages, and supplements combined is 2,000 mg/day for adults [9][12]. This is based primarily on the risk of gastrointestinal disturbances. ULs for other age groups:

Age	UL (mg/day)
1-3 years	400
4-8 years	650
9-13 years	1,200
14-18 years	1,800
19+ years	2,000

Practical Dosing by Purpose

General supplementation (to fill dietary gaps): 75-200 mg/day. This range meets the RDA and approaches tissue saturation levels. Most people eating 5 varied servings of fruits and vegetables daily will obtain more than 200 mg from diet alone [9][12].

Cold prevention/immune support: 200-1,000 mg/day, ideally taken as divided doses (e.g., 500 mg twice daily). Regular daily use during cold season has the best evidence. Starting after symptoms begin is not effective [38][39].

Blood pressure support: 500-1,000 mg/day, based on the meta-analysis showing modest reductions. Effects are small relative to pharmaceutical treatment [51].

Gout/uric acid reduction: 500 mg/day. The uric acid-lowering effect plateaus around 400-500 mg/day with no further benefit at higher doses [104].

AREDS formula (AMD progression): 500 mg/day as part of the AREDS combination supplement, recommended only for people with intermediate or advanced AMD in one eye [101][102].

Smokers: RDA + 35 mg/day (125 mg for men, 110 mg for women). Higher supplementation may be beneficial for those who smoke, as they experience increased oxidative stress depleting vitamin C stores [12].

How to Read a Supplement Label

When looking for vitamin C dosage, be aware that 1,000 mcg (micrograms) = 1 mg (milligram), and 1,000 mg = 1 gram. The weight listed is typically the weight of the vitamin C itself [6]:

• "500 mg vitamin C as calcium ascorbate" means 500 mg of actual vitamin C, plus additional calcium weight.
• Check the "% Daily Value" on the Supplement Facts label. The DV for vitamin C is 90 mg for adults and children aged 4+ [123].

Timing and Absorption Tips

• Take with food to slow gastrointestinal transit and reduce stomach upset from acidic forms.
• Divide doses when taking more than 200 mg/day to maximize absorption, since fractional absorption declines at higher single doses. Ingestion of several smaller doses each day is preferable to a single large dose [7][24].
• Store properly: Keep vitamin C in a closed container away from direct light. Exposure to air and light causes oxidation, converting some reduced vitamin C to dehydroascorbic acid, which may not function as effectively [6].

5. Dietary Sources

Fruits and vegetables are the best sources of vitamin C. Consuming 5 varied servings of fruits and vegetables per day typically provides more than 200 mg [9][12].

Top Food Sources

Food	Serving	Vitamin C (mg)	% DV (90 mg)
Red bell pepper, raw	1/2 cup	95	106%
Orange juice	3/4 cup	93	103%
Orange	1 medium	70	78%
Grapefruit juice	3/4 cup	70	78%
Kiwifruit	1 medium	64	71%
Green bell pepper, raw	1/2 cup	60	67%
Broccoli, cooked	1/2 cup	51	57%
Strawberries, fresh, sliced	1/2 cup	49	54%
Brussels sprouts, cooked	1/2 cup	48	53%
Grapefruit	1/2 medium	39	43%
Tomato juice	3/4 cup	33	37%
Cantaloupe	1/2 cup	29	32%
Cabbage, cooked	1/2 cup	28	31%
Cauliflower, raw	1/2 cup	26	29%
Potato, baked	1 medium	17	19%
Tomato, raw	1 medium	17	19%
Spinach, cooked	1/2 cup	9	10%

Source: USDA FoodData Central [124].

Practical Notes on Dietary Vitamin C

• Cooking reduces vitamin C content because ascorbic acid is water-soluble and destroyed by heat. Prolonged storage also reduces levels. Steaming or microwaving causes less loss than boiling [9][10][12].
• Raw consumption preserves vitamin C. Many of the best food sources (bell peppers, citrus, strawberries, kiwi) are commonly eaten raw.
• Citrus fruits, potatoes, and tomato juice are the major contributors of vitamin C to the American diet [12].
• Food-first approach: Meeting the RDA through diet is readily achievable with consistent intake of fruits and vegetables. However, vitamin C content varies with storage and cooking, so supplementation can serve as insurance.
• Vitamin C is added to some fortified breakfast cereals [12].
• Most Americans have sufficient intake: According to NHANES data, mean intakes from food and beverages are 105.2 mg/day for adult males and 83.6 mg/day for adult females, meeting the RDA for most nonsmoking adults [12].

6. Safety and Side Effects

Common Side Effects

The primary side effects of oral vitamin C supplementation are gastrointestinal disturbances, typically at higher doses [4][9][12]:

• Diarrhea: Caused by the osmotic effect of unabsorbed vitamin C drawing water into the intestinal lumen. This is dose-dependent and unrelated to the acidity of the supplement form. Non-acidic forms (calcium ascorbate, sodium ascorbate) prevent heartburn but do not prevent diarrhea.
• Nausea, abdominal cramps, and heartburn: More common at higher doses, particularly with acidic ascorbic acid. Taking with food and dividing doses throughout the day reduces these effects.
• Dental enamel erosion: Vitamin C (as ascorbic acid) is acidic and can damage teeth if held in the mouth for extended periods. Chewable tablets pose the highest risk [6].

The UL of 2,000 mg/day is based on these gastrointestinal effects, not on systemic toxicity. In general, vitamin C has low toxicity and is not believed to cause serious adverse effects at high intakes in healthy individuals [9][12].

Kidney Stones

This is the most significant safety concern for men taking high-dose vitamin C supplements. Vitamin C is partly metabolized to oxalate, and excess oxalate can form calcium oxalate stones. Vitamin C may also increase oxalate absorption from foods [125].

• A Swedish study found the risk of kidney stones was 66% higher for men taking an estimated 1,000 mg vitamin C occasionally, and 123% higher for those taking it 7+ times per week [126].
• A US study found the risk was 16% higher among men consuming 1,000 mg or more per day from supplements [127].
• An analysis of three observational studies found 1,000 mg/day or more from supplements was associated with 19% increased risk among men versus intake below 90 mg daily. There was no such association for women, nor with dietary vitamin C intake in either sex [128].

Kidney stone risk is primarily a concern for men. Women do not appear to face increased risk from vitamin C supplementation based on available data [128]. The best evidence for increased stone risk is in patients with pre-existing hyperoxaluria [9].

Oxalate Nephropathy

Vitamin C intake above 2,000 mg/day may cause oxalate crystal nephropathy — oxalate crystal deposition in kidney tubules and tissue, leading to kidney damage and/or failure. This may be more likely in people with [6][50]:

• Pre-existing kidney disease
• Pancreatic insufficiency (which, due to fat malabsorption, allows increased oxalate absorption in the colon — a case report described a man in his 80s with pancreatic insufficiency who developed oxalate nephropathy and end-stage kidney disease requiring dialysis from 1,000-2,000 mg vitamin C [129])
• Bowel inflammation or celiac disease
• Enlarged prostate (benign prostatic hyperplasia)
• High concurrent intake of oxalate-rich foods (nuts, spinach)

Oxalate nephropathy has been reported at daily doses as low as 480 mg, with onset ranging from one month to several years of supplementation [130]. A man in his 80s with stage 4 chronic kidney disease developed acute kidney injury from oxalate nephropathy after taking 2,000 mg/day for several years, compounded by increased nut consumption containing approximately 242 mg of oxalate per serving several times per day [131].

For men, people with a history of kidney stones, or those with known defects in oxalate or vitamin C metabolism, it may be wise to limit supplemental vitamin C to RDA levels (75-90 mg) or no more than 250 mg per day [125].

Cataract Risk

Long-term supplementation with approximately 1,000 mg/day has been associated with a 25-46% increased risk of cataract removal in women, depending on duration of use [95]. Low-to-moderate doses (60-250 mg/day) may be protective rather than harmful (see Section 3).

Iron Overload Risk

Vitamin C enhances nonheme iron absorption. In healthy individuals, this does not appear to be a concern [9][12]. However, in individuals with hereditary hemochromatosis, chronic high-dose vitamin C consumption could exacerbate iron overload and result in tissue damage [4][9][12].

Copper Depletion

High doses of vitamin C may modestly decrease copper levels. Young healthy men who took 1,500 mg/day (500 mg three times daily) for 2 months experienced significantly reduced ceruloplasmin activity (the protein that stores and transports copper). Blood copper levels also decreased but not significantly [132]. A separate study found that 635 mg/day for 1 month decreased ceruloplasmin activity, while lower doses (5-635 mg/day) did not decrease blood copper levels [133].

Pro-oxidant Activity

Under certain conditions, vitamin C can act as a pro-oxidant, potentially contributing to oxidative damage [9]. In vitro studies have suggested that supplemental vitamin C could cause chromosomal and/or DNA damage and possibly contribute to cancer development [9][134][135]. However, other studies have not shown increased oxidative damage or cancer risk with high intakes [9][136], and the in vivo relevance of these findings is unclear.

Interference with Diagnostic Tests

Vitamin C supplements at 250 mg or more can interfere with several diagnostic tests [6]:

• Fecal occult blood tests (gFOBT): Vitamin C can cause false-negative results on traditional guaiac-based tests (Hemoccult). Stop vitamin C (and other antioxidant supplements, red meat, and vegetables high in peroxidase such as broccoli, cauliflower, and radishes) 3 days before sample collection. Newer fecal immunochemical tests (FIT) such as Hema Select, FlexSure, and Insure are NOT affected by vitamin C and are recommended over gFOBT by the American College of Gastroenterology [137].
• Urine tests: Vitamin C may interfere with dipstick and biochemical urine tests measuring bilirubin, glucose, leukocyte esterase, hemoglobin, nitrite, calcium, chloride, and magnesium. Reported at doses ranging from 350-1,000 mg/day [138][139][140][141].
• Blood tests: Excess vitamin C may interfere with measurements of cholesterol and blood sugar levels [6].

Other Reported Effects

Other reported effects of high vitamin C intake include reduced vitamin B12 levels, accelerated metabolism or excretion of ascorbic acid, erosion of dental enamel, and allergic responses. However, at least some of these findings were artifacts of assay methodology, and additional studies have not confirmed them [9].

Special Populations

Smokers: Require an additional 35 mg/day. Those exposed to secondhand smoke should also ensure they meet the RDA [12].

Infants: Should receive vitamin C from breastmilk or infant formula. Evaporated or boiled cow's milk should not be fed to infants, as cow's milk has very little vitamin C and heat destroys it [10][12].

People with hemochromatosis: Should avoid high-dose vitamin C due to enhanced iron absorption [4][9][12].

End-stage renal disease: Low vitamin C concentrations occur in patients on chronic hemodialysis [13], but supplementation requires caution due to oxalate accumulation risk.

Interstitial cystitis: Some patients report that vitamin C and citrus products cause irritation [142].

7. Drug Interactions

Vitamin C supplements can interact with several medications. The most clinically important interactions are summarized below.

Medications Affected by Vitamin C

Drug	Interaction	Clinical Recommendation
Levothyroxine (Synthroid)	Vitamin C may increase absorption by increasing gastric acid secretion. A 6-week study found 1 g/day of vitamin C with levothyroxine reduced TSH from 9.01 to 2.27 mU/L in hypothyroid patients [143].	People on stable levothyroxine doses should consult their doctor before starting vitamin C.
Warfarin	An early 1971 case report suggested interference [144], but subsequent research has not confirmed this. 1 g/day for 6 months did not affect warfarin requirements [145]. Doses of 3-10 g/day for 7 days in 19 adults on warfarin did not affect prothrombin ratios, though blood warfarin levels decreased by approximately 17.5% (not considered clinically significant) [146]. 2 g/day for 6 weeks did not increase bleeding risk in healthy men [147].	Current evidence does not support a clinically significant interaction.
Indinavir (HIV drug)	High-dose vitamin C may reduce effectiveness [148].	Discuss with prescriber.
Tricyclic antidepressants	Vitamin C may reduce absorption [6].	Consider separating dosing times.
Acetaminophen (Tylenol)	The risk of liver damage from high acetaminophen doses may increase with very large (3 g) vitamin C doses [6].	Avoid combining high doses of both.

Vitamin C and Statins

A study of people with heart disease and low HDL cholesterol found that 1,000 mg/day vitamin C combined with other antioxidants (800 IU vitamin E, 25 mg beta-carotene, 100 mcg selenium) reduced the cholesterol-lowering effects of simvastatin taken with high-dose niacin (2,000 mg) [149]. However, it is unclear whether vitamin C alone was responsible, whether this would occur with other statins, or without high-dose niacin. Current prescribing information for simvastatin, atorvastatin (Lipitor), lovastatin, and rosuvastatin (Crestor) does not note an interaction with vitamin C, but does warn against combining with high-dose niacin (>1,000 mg/day) due to rhabdomyolysis risk [6].

Chemotherapy and Radiation

The safety and efficacy of vitamin C during cancer treatment is controversial. Some data indicate antioxidants might protect tumor cells from radiation and chemotherapy agents including cyclophosphamide, chlorambucil, carmustine, busulfan, thiotepa, and doxorubicin [87][88][89]. Other data suggest antioxidants might protect normal tissues or enhance treatment [90][91]. Due to the physiologically tight control of vitamin C, it is unclear whether oral supplements could alter concentrations enough to produce these effects. Patients undergoing chemotherapy or radiation should consult their oncologist before taking vitamin C [87].

Medications That Affect Vitamin C Status

Drug	Effect	Notes
Aspirin (high-dose, 12+ tablets/day)	May lower vitamin C levels	Supplementing with vitamin C normalizes levels [150].
Proton pump inhibitors (long-term)	Increase scurvy risk	Long-term PPI use has been implicated in vitamin C deficiency cases [6].

Pycnogenol Interaction

One study found that taking vitamin C along with Pycnogenol (pine bark extract/OPCs) might raise blood pressure in people with hypertension. The reasons are currently unclear [6].

References

1. Li Y, Schellhorn HE. "New developments and novel therapeutic perspectives for vitamin C." J Nutr. 2007;137:2171-84. https://pubmed.ncbi.nlm.nih.gov/17884994/

2. Carr AC, Frei B. "Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans." Am J Clin Nutr. 1999;69:1086-107. https://pubmed.ncbi.nlm.nih.gov/10357726/

3. Frei B, England L, Ames BN. "Ascorbate is an outstanding antioxidant in human blood plasma." Proc Natl Acad Sci USA. 1989;86:6377-81. https://pubmed.ncbi.nlm.nih.gov/2762330/

4. Jacob RA, Sotoudeh G. "Vitamin C function and status in chronic disease." Nutr Clin Care. 2002;5:66-74. https://pubmed.ncbi.nlm.nih.gov/12134712/

5. Gershoff SN. "Vitamin C (ascorbic acid): new roles, new requirements?" Nutr Rev. 1993;51:313-26. https://pubmed.ncbi.nlm.nih.gov/8108051/

6. ConsumerLab. "Vitamin C Supplements Review." Accessed 2025. https://www.consumerlab.com/reviews/vitamin-c-supplement-review/vitaminc/

7. Padayatty SJ, Sun H, Wang Y, et al. "Vitamin C pharmacokinetics: implications for oral and intravenous use." Ann Intern Med. 2004;140:533-7. https://pubmed.ncbi.nlm.nih.gov/15068981/

8. Padayatty SJ, Riordan HD, Hewitt SM, et al. "Intravenously administered vitamin C as cancer therapy: three cases." CMAJ. 2006;174:937-42. https://pubmed.ncbi.nlm.nih.gov/16567755/

9. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000.

10. Weinstein M, Babyn P, Zlotkin S. "An orange a day keeps the doctor away: scurvy in the year 2000." Pediatrics. 2001;108:E55. https://pubmed.ncbi.nlm.nih.gov/11533373/

11. Wang AH, Still C. "Old world meets modern: a case report of scurvy." Nutr Clin Pract. 2007;22:445-8. https://pubmed.ncbi.nlm.nih.gov/17644698/

12. NIH Office of Dietary Supplements. "Vitamin C — Health Professional Fact Sheet." https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/

13. Deicher R, Horl WH. "Vitamin C in chronic kidney disease and hemodialysis patients." Kidney Blood Press Res. 2003;26:100-6. https://pubmed.ncbi.nlm.nih.gov/12771534/

14. Hujoel PP, et al. "Bleeding tendency and ascorbic acid requirements." Nutr Rev. 2021. doi: 10.1093/nutrit/nuaa115

15. Stapleton FB, et al. "Vitamin C deficiency mimicking juvenile arthritis." J Pediatr. 2019.

16. Shameek G, et al. "Vitamin C deficiency and pulmonary arterial hypertension." Chest. 2020.

17. Mangels AR, Block G, Frey CM, et al. "The bioavailability to humans of ascorbic acid from oranges, orange juice and cooked broccoli is similar to that of synthetic ascorbic acid." J Nutr. 1993;123:1054-61. https://pubmed.ncbi.nlm.nih.gov/8505666/

18. Johnston CS, Luo B. "Comparison of the absorption and excretion of three commercially available sources of vitamin C." J Am Diet Assoc. 1994;94:779-81. https://pubmed.ncbi.nlm.nih.gov/8021423/

19. Moyad MA, Combs MA, Vrablic AS, et al. "Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations." Adv Ther. 2008;25:995-1009. https://pubmed.ncbi.nlm.nih.gov/18836695/

20. Purpura M, et al. "Liposomal vitamin C bioavailability." Eur J Nutr. 2024.

21. Hickey S, et al. "Pharmacokinetics of oral vitamin C." J Nutri Envir Med. 2008.

22. Ashil J, et al. "Liposomal hydrogel vitamin C absorption." RSC Adv. 2021.

23. Pancorbo D, et al. "PureWay-C vitamin C bioavailability." Med Sci Monit. 2008.

24. Carr AC, et al. "Vitamin C pharmacokinetics and bioavailability." Nutrients. 2013.

25. Vinson JA, et al. "Bioavailability of vitamin C with bioflavonoids." Am J Clin Nutr. 1988.

26. Pullar JM, et al. "The roles of vitamin C in skin health." Nutrients. 2017.

27. Rhie G, et al. "Vitamin C levels in aged skin." J Invest Dermatol. 2001.

28. Pinnell SR. "Cutaneous photodamage, oxidative stress, and topical antioxidant protection." Dermatol Surg. 2001.

29. Levine M, Conry-Cantilena C, Wang Y, et al. "Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance." Proc Natl Acad Sci USA. 1996;93:3704-9. https://pubmed.ncbi.nlm.nih.gov/8623000/

30. Lin JY, et al. "Vitamin C and vitamin E combination for UV protection." J Am Acad Dermatol. 2003.

31. Lin FH, et al. "Ferulic acid stabilizes vitamins C and E topical formulation." J Invest Dermatol. 2005.

32. Humbert PG, et al. "Topical ascorbic acid on photo-aged skin." Exp Dermatol. 2003.

33. Darr D, et al. "Effectiveness of antioxidants (vitamins C and E) with and without sunscreens as topical photoprotectants." Acta Derm Venereol. 1996.

34. Murray JC, et al. "A topical antioxidant solution containing vitamins C and E." J Am Acad Dermatol. 2008.

35. Grether-Beck S, et al. "Photoprotection of human skin beyond ultraviolet radiation." Photochem Photobiol. 2015.

36. Dreher F, et al. "Topical vitamin C and UV-induced erythema." Br J Dermatol. 1998.

37. Pauling L. "The significance of the evidence about ascorbic acid and the common cold." Proc Natl Acad Sci USA. 1971;68:2678-81. https://pubmed.ncbi.nlm.nih.gov/4941984/

38. Hemila H, Chalker E. "Vitamin C for preventing and treating the common cold." Cochrane Database Syst Rev. 2013. https://pubmed.ncbi.nlm.nih.gov/23440782/

39. Johnston CS, et al. "Vitamin C supplementation and cold symptoms." Nutrients. 2014.

40. Ran L, et al. "Extra dose of vitamin C and duration of the common cold." Biomed Res Int. 2018 (retracted 2023).

41. Wintergerst ES, Maggini S, Hornig DH. "Immune-enhancing role of vitamin C and zinc and effect on clinical conditions." Ann Nutr Metab. 2006;50:85-94. https://pubmed.ncbi.nlm.nih.gov/16373990/

42. Hemila H. "The role of vitamin C in the treatment of the common cold." Am Fam Physician. 2007;76:1111. https://pubmed.ncbi.nlm.nih.gov/17990834/

43. Johnston CS. "The antihistamine action of ascorbic acid." Subcell Biochem. 1996;25:189-213. https://pubmed.ncbi.nlm.nih.gov/8821975/

44. Thomas S, et al. "Effect of high-dose zinc and vitamin C on COVID-19 symptom duration." JAMA Network Open. 2021.

45. Fogleman C, et al. "Vitamin C for mild to moderate COVID-19." J Am Board Fam Med. 2022.

46. Seymour CW, et al. "Effect of high-dose vitamin C on organ failure and mortality in critically ill patients with COVID-19." JAMA Network. 2023.

47. Zhang J, et al. "Pilot trial of high-dose vitamin C in critically ill COVID-19 patients." Ann Intensive Care. 2021.

48. Chaudhary S, et al. "High-dose vitamin C in critically ill COVID-19 patients." Acute Crit Care. 2020.

49. Hemila H. "Vitamin C and mechanical ventilation." J Intensive Care. 2020.

50. Fong D, et al. "Oxalate nephropathy and vitamin C supplementation during the COVID-19 pandemic." Kidney Int Rep. 2022.

51. Juraschek SP, et al. "Effects of vitamin C supplementation on blood pressure: a meta-analysis." Am J Clin Nutr. 2012.

52. Dow CA, et al. "Vitamin C and endothelin-1 activity in overweight adults." Am Phys Soc Conf. 2015.

53. Mason SA, et al. "Vitamin C supplementation in type 2 diabetes." Diab Obes Metab. 2019.

54. Ye Z, Song H. "Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies." Eur J Cardiovasc Prev Rehabil. 2008;15:26-34. https://pubmed.ncbi.nlm.nih.gov/18277182/

55. Willcox BJ, Curb JD, Rodriguez BL. "Antioxidants in cardiovascular health and disease: key lessons from epidemiologic studies." Am J Cardiol. 2008;101:75D-86D. https://pubmed.ncbi.nlm.nih.gov/18474276/

56. Honarbakhsh S, Schachter M. "Vitamins and cardiovascular disease." Br J Nutr. 2008. https://pubmed.ncbi.nlm.nih.gov/18847518/

57. Osganian SK, Stampfer MJ, Rimm E, et al. "Vitamin C and risk of coronary heart disease in women." J Am Coll Cardiol. 2003;42:246-52. https://pubmed.ncbi.nlm.nih.gov/12875759/

58. Myint PK, Luben RN, Welch AA, et al. "Plasma vitamin C concentrations predict risk of incident stroke over 10 y." Am J Clin Nutr. 2008;87:64-9. https://pubmed.ncbi.nlm.nih.gov/18175738/

59. Knekt P, Ritz J, Pereira MA, et al. "Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts." Am J Clin Nutr. 2004;80:1508-20. https://pubmed.ncbi.nlm.nih.gov/15585762/

60. Muntwyler J, Hennekens CH, Manson JE, et al. "Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality." Arch Intern Med. 2002;162:1472-6. https://pubmed.ncbi.nlm.nih.gov/12090883/

61. Cook NR, Albert CM, Gaziano JM, et al. "A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women." Arch Intern Med. 2007;167:1610-8. https://pubmed.ncbi.nlm.nih.gov/17698683/

62. Sesso HD, Buring JE, Christen WG, et al. "Vitamins E and C in the prevention of cardiovascular disease in men." JAMA. 2008;300:2123-33. https://pubmed.ncbi.nlm.nih.gov/18997197/

63. Hercberg S, Galan P, Preziosi P, et al. "The SU.VI.MAX Study." Arch Intern Med. 2004;164:2335-42. https://pubmed.ncbi.nlm.nih.gov/15557412/

64. Waters DD, Alderman EL, Hsia J, et al. "Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women." JAMA. 2002;288:2432-40. https://pubmed.ncbi.nlm.nih.gov/12435256/

65. Bleys J, Miller ER 3rd, Pastor-Barriuso R, et al. "Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis." Am J Clin Nutr. 2006;84:880-7. https://pubmed.ncbi.nlm.nih.gov/17023716/

66. Qiao YL, Dawsey SM, Kamangar F, et al. "Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian trial." J Natl Cancer Inst. 2009;101:507-18. https://pubmed.ncbi.nlm.nih.gov/19318634/

67. Goyal A, et al. "Serum vitamin C and mortality." Cancer Epidemiol Biomarkers Prev. 2013.

68. Tian Y, et al. "Vitamin C blood levels and all-cause mortality." Nutrition. 2022.

69. Lee DH, Folsom AR, Harnack L, et al. "Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes?" Am J Clin Nutr. 2004;80:1194-200. https://pubmed.ncbi.nlm.nih.gov/15531664/

70. Zhang S, Hunter DJ, Forman MR, et al. "Dietary carotenoids and vitamins A, C, and E and risk of breast cancer." J Natl Cancer Inst. 1999;91:547-56. https://pubmed.ncbi.nlm.nih.gov/10088626/

71. Kushi LH, Fee RM, Sellers TA, et al. "Intake of vitamins A, C, and E and postmenopausal breast cancer." Am J Epidemiol. 1996;144:165-74. https://pubmed.ncbi.nlm.nih.gov/8678048/

72. Gaziano JM, Glynn RJ, Christen WG, et al. "Vitamins E and C in the prevention of prostate and total cancer in men." JAMA. 2009;301:52-62. https://pubmed.ncbi.nlm.nih.gov/19066368/

73. Lin J, Cook NR, Albert C, et al. "Vitamins C and E and beta carotene supplementation and cancer risk." J Natl Cancer Inst. 2009;101:14-23. https://pubmed.ncbi.nlm.nih.gov/19116389/

74. Galan P, Briancon S, Favier A, et al. "Antioxidant status and risk of cancer in the SU.VI.MAX study." Br J Nutr. 2005;94:125-32. https://pubmed.ncbi.nlm.nih.gov/16115340/

75. Taylor PR, Li B, Dawsey SM, et al. "Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China." Cancer Res. 1994;54(7 Suppl):2029s-31s. https://pubmed.ncbi.nlm.nih.gov/8137331/

76. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. "Antioxidant supplements for preventing gastrointestinal cancers." Cochrane Database Syst Rev. 2008;(3):CD004183. https://pubmed.ncbi.nlm.nih.gov/18677777/

77. Parent ME, et al. "Vitamin C intake and prostate cancer." Front Physiol. 2018.

78. Cadeau C, et al. "Vitamin C intake from food and supplements and breast cancer risk." Am J Clin Nutr. 2016.

79. Cameron E, Campbell A. "The orthomolecular treatment of cancer. II." Chem Biol Interact. 1974;9:285-315. https://pubmed.ncbi.nlm.nih.gov/4430016/

80. Cameron E, Pauling L. "Supplemental ascorbate in the supportive treatment of cancer." Proc Natl Acad Sci USA. 1976;73:3685-9. https://pubmed.ncbi.nlm.nih.gov/1068480/

81. Moertel CG, Fleming TR, Creagan ET, et al. "High-dose vitamin C versus placebo in the treatment of patients with advanced cancer." N Engl J Med. 1985;312:137-41. https://pubmed.ncbi.nlm.nih.gov/3880867/

82. Coulter I, Hardy M, Shekelle P, et al. "Effect of the supplemental use of antioxidants vitamin C, vitamin E, and coenzyme Q10 for the prevention and treatment of cancer." AHRQ Publication No. 04-E003. 2003. https://pubmed.ncbi.nlm.nih.gov/15468265/

83. Chen Q, Espey MG, Sun AY, et al. "Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice." Proc Natl Acad Sci USA. 2008;105:11105-9. https://pubmed.ncbi.nlm.nih.gov/18678913/

84. Chen Q, Espey MG, Krishna MC, et al. "Pharmacologic ascorbic acid concentrations selectively kill cancer cells." Proc Natl Acad Sci USA. 2005;102:13604-9. https://pubmed.ncbi.nlm.nih.gov/16157892/

85. Chen Q, Espey MG, Sun AY, et al. "Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo." Proc Natl Acad Sci USA. 2007;104:8749-54. https://pubmed.ncbi.nlm.nih.gov/17502596/

86. Levine M, Espey MG, Chen Q. "Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment." Free Radic Biol Med. 2009;47:27-9. https://pubmed.ncbi.nlm.nih.gov/19361557/

87. Lawenda BD, Kelly KM, Ladas EJ, et al. "Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?" J Natl Cancer Inst. 2008;100:773-83. https://pubmed.ncbi.nlm.nih.gov/18505970/

88. Seifried HE, Anderson DE, Sorkin BC, Costello RB. "Free radicals: the pros and cons of antioxidants." J Nutr. 2004;134:3143S-63S. https://pubmed.ncbi.nlm.nih.gov/15514289/

89. Heaney ML, Gardner JR, Karasavvas N, et al. "Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs." Cancer Res. 2008;68:8031-8. https://pubmed.ncbi.nlm.nih.gov/18829561/

90. Ladas EJ, Jacobson JS, Kennedy DD, et al. "Antioxidants and cancer therapy: a systematic review." J Clin Oncol. 2004;22:517-28. https://pubmed.ncbi.nlm.nih.gov/14752075/

91. Block KI, Koch AC, Mead MN, et al. "Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review." Cancer Treat Rev. 2007;33:407-18. https://pubmed.ncbi.nlm.nih.gov/17367938/

92. Yonova-Doing E, et al. "Genetic and dietary factors influencing the progression of nuclear cataract." Ophthalmology. 2016.

93. Jacques PF, et al. "Long-term vitamin C supplement use and cataract risk." Am J Clin Nutr. 1997.

94. Yoshida M, Takashima Y, Inoue M, et al. "Prospective study showing that dietary vitamin C reduced the risk of age-related cataracts in a middle-aged Japanese population." Eur J Nutr. 2007;46:118-24. https://pubmed.ncbi.nlm.nih.gov/17265171/

95. Rautiainen S, Lindblad BE, Morgenstern R, Wolk A. "Vitamin C supplements and the risk of age-related cataract." Am J Clin Nutr. 2010;91(2):487-93. https://pubmed.ncbi.nlm.nih.gov/20016012/

96. Age-Related Eye Disease Study Research Group. "AREDS report no. 9." Arch Ophthalmol. 2001;119:1439-52. https://pubmed.ncbi.nlm.nih.gov/11594943/

97. Age-Related Eye Disease Study 2 Research Group. "AREDS2 report no. 4." JAMA Ophthalmol. 2013. https://pubmed.ncbi.nlm.nih.gov/23644932/

98. Chong EW, Wong TY, Kreis AJ, et al. "Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis." BMJ. 2007;335:755. https://pubmed.ncbi.nlm.nih.gov/17923720/

99. van Leeuwen R, Boekhoorn S, Vingerling JR, et al. "Dietary intake of antioxidants and risk of age-related macular degeneration." JAMA. 2005;294:3101-7. https://pubmed.ncbi.nlm.nih.gov/16380590/

100. Evans J. "Primary prevention of age related macular degeneration." BMJ. 2007;335:729. https://pubmed.ncbi.nlm.nih.gov/17916811/

101. Age-Related Eye Disease Study Research Group. "AREDS report no. 8." Arch Ophthalmol. 2001;119:1417-36. https://pubmed.ncbi.nlm.nih.gov/11594942/

102. Age-Related Eye Disease Study 2 Research Group. "AREDS2 randomized clinical trial." JAMA. 2013;309:2005-15. https://pubmed.ncbi.nlm.nih.gov/23644932/

103. Choi HK, et al. "Vitamin C intake and the risk of gout in men." Arch Intern Med. 2009.

104. Gao X, et al. "Vitamin C intake and serum uric acid." J Rheumatol. 2008.

105. Enderle J, et al. "Vitamin C beverage and serum uric acid." Eur J Nutr. 2026.

106. Wei J, et al. "Vitamin C intake and NAFLD." PLOS One. 2016.

107. He H, et al. "Vitamin C supplementation in NAFLD." Front Nutr. 2021.

108. Harrison FE, et al. "Vitamin C and the brain." Free Radic Biol Med. 2010.

109. Moret C, et al. "Norepinephrine and depression." Neuropsychiatry Dis Treat. 2011.

110. Wang X, et al. "Dietary vitamin C and depressive symptoms." Antioxidants. 2021.

111. Sim M, et al. "Vitamin C supplementation and mood in young adults." Eur J Nutr. 2021.

112. Conner TS, et al. "Vitamin C, kiwifruit, and mood." Nutrients. 2020.

113. Chen JY, et al. "Low vitamin C and post-herpetic neuralgia." Br J Nutr. 2011.

114. Carr AC, et al. "Intravenous vitamin C and herpes zoster pain." J Transl Med. 2017.

115. Kim MS, et al. "Intravenous vitamin C in herpes zoster." Ann Dermatol. 2016.

116. Gunton JE, et al. "Vitamin C and diabetic foot ulcer healing." Brit J Nutr. 2020.

117. Maurilio TL, et al. "Vitamin C and E supplementation during strength training in women." Int J Exerc Sci. 2019.

118. Paulsen G, et al. "Vitamin C and E supplementation hampers cellular adaptation to endurance training." J Physiol. 2014.

119. Stunes AK, et al. "High-dose antioxidants constrain skeletal benefits of resistance training in elderly men." Eur J Appl Phys. 2017.

120. Sarkar S, et al. "Vitamin C and E supplementation during HIIT in athletes." SMHS. 2023.

121. Cashman MW, et al. "Nutrition and nail disease." Clin Dermatol. 2010.

122. Scheinfeld NS, et al. "Vitamins and minerals and nails." J Drugs Dermatol. 2007.

123. U.S. Food and Drug Administration. "Food Labeling: Revision of the Nutrition and Supplement Facts Labels." 2016.

124. U.S. Department of Agriculture, Agricultural Research Service. FoodData Central, 2019. https://fdc.nal.usda.gov/

125. Massey LK, et al. "Ascorbate increases human oxaluria and kidney stone risk." Frontiers in Bioscience. 2003;8:s584-6.

126. Thomas LDK, et al. "Ascorbic acid supplements and kidney stone incidence among men." JAMA Intern Med. 2013.

127. Taylor EN, Stampfer MJ, Curhan GC. "Dietary factors and the risk of incident kidney stones in men." J Am Soc Nephrol. 2004;15:3225-32. https://pubmed.ncbi.nlm.nih.gov/15579526/

128. Ferraro PM, et al. "Vitamin C supplements and kidney stone risk." Am J Kidney Dis. 2016.

129. Fijen LM, et al. "Oxalate nephropathy from high-dose vitamin C." BMJ Case Rep. 2019.

130. Lin Y, et al. "Vitamin C-induced oxalate nephropathy." CEN Case Rep. 2018.

131. Pal R, et al. "Oxalate nephropathy from vitamin C and dietary oxalate." Clin Nephrol Case Stud. 2024.

132. Finley EB, et al. "High-dose vitamin C and copper metabolism." Am J Clin Nutr. 1983.

133. Jacob RA, et al. "Vitamin C and copper." J Nutr. 1987.

134. Lee SH, Oe T, Blair IA. "Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins." Science. 2001;292:2083-6. https://pubmed.ncbi.nlm.nih.gov/11408659/

135. Podmore ID, Griffiths HR, Herbert KE, et al. "Vitamin C exhibits pro-oxidant properties." Nature. 1998;392:559. https://pubmed.ncbi.nlm.nih.gov/9560150/

136. Carr A, Frei B. "Does vitamin C act as a pro-oxidant under physiological conditions?" FASEB J. 1999;13:1007-24. https://pubmed.ncbi.nlm.nih.gov/10336883/

137. Rex DK, et al. "Colorectal cancer screening recommendations." Am J Gastroenterol. 2009.

138. Lee W, et al. "Vitamin C interference with urine dipstick tests." J Clin Lab Anal. 2017.

139. Unic A, et al. "Effect of ascorbic acid on urine test parameters." J Clin Lab Anal. 2018.

140. Gabaj NN, et al. "Ascorbic acid interference with urinalysis." Annals of Clinical Biochemistry. 2020.

141. Maskovic J, et al. "Vitamin C interference with urine mineral measurement." Lab Med. 2024.

142. Friedlander JI, et al. "Diet and interstitial cystitis." BJU Int. 2012.

143. Antunez PB, et al. "Vitamin C and levothyroxine absorption." Rev Argent Endocrinol Metab. 2011.

144. Rosenthal G. "Interaction of ascorbic acid and warfarin." JAMA. 1971.

145. Dedichen HG, et al. "Vitamin C and warfarin anticoagulant therapy." Boll Soc Ital Cardiol. 1973.

146. Feetam CL, et al. "Vitamin C and warfarin pharmacokinetics." Toxicol Appl Pharmacol. 1975.

147. Tofler GH, et al. "Effect of vitamin C on hemostasis." Thromb Res. 2000.

148. Slain D, et al. "Effect of high-dose vitamin C on steady-state pharmacokinetics of indinavir." Pharmacotherapy. 2005.

149. Cheung MC, Zhao XQ, Chait A, et al. "Antioxidant supplements block the response of HDL to simvastatin-niacin therapy." Arterioscler Thromb Vasc Biol. 2001;21:1320-6. https://pubmed.ncbi.nlm.nih.gov/11498460/

150. Sahud MA, et al. "Aspirin and vitamin C levels." Lancet. 1971.