En Español
Health Encyclopedia

Nutritional Supplement

Vitamin C

  • Immune System Support

    Common Cold and Sore Throat

    Studies have shown that taking vitamin C may make your cold shorter and less severe.
    Common Cold and Sore Throat
    ×
     

    A review of 21 controlled trials using 1 to 8 grams of vitamin C per day found that “in each of the twenty-one studies, vitamin C reduced the duration of episodes and the severity of the symptoms of the common cold by an average of 23%.”1 The optimum amount of vitamin C to take for cold treatment remains in debate but may be as high as 1 to 3 grams per day, considerably more than the 120 to 200 mg per day that has been suggested as optimal intake for healthy adults. A review of 23 controlled trials found that vitamin C supplementation produces a greater benefit for children than for adults.2 The same review found that a daily amount of 2 grams or more was superior to a daily amount of 1 gram at reducing the duration of cold symptoms.

    Infection

    Vitamin C has antiviral activity, and may help prevent viral infections or, in the case of the common cold, reduce the severity and duration of an infection.
    Infection
    ×
     

    Vitamin C has antiviral activity, and may help prevent viral infections3 or, in the case of the common cold, reduce the severity and duration of an infection.4 Most studies on the common cold used 1 to 4 grams of vitamin C per day.

    Bronchitis

    In a double-blind study of elderly patients hospitalized with acute bronchitis, those given vitamin C improved to a significantly greater extent than those who were given a placebo.
    Bronchitis
    ×
     

    In a double-blind study of elderly patients hospitalized with acute bronchitis, those who were given 200 mg per day of vitamin C improved to a significantly greater extent than those who were given a placebo.5 The common cold may lead to bronchitis in susceptible people, and numerous controlled studies, some double-blind, have shown that vitamin C supplements can decrease the severity and duration of the common cold in otherwise healthy people.6

    Vitamin C and vitamin E may prevent oxidative damage to the lung lipids by environmental pollution and cigarette smoke exposure. It has been suggested that amounts in excess of the RDA (recommended dietary allowance) are necessary to protect against the air pollution levels currently present in North America,7 although it is not known how much vitamin E is needed to produce that protective effect.

    Immune Function

    Vitamin C stimulates the immune system. While taking it has only a small effect in preventing colds, it does significantly reduce the duration of a cold when taken at the onset.
    Immune Function
    ×

    Most,8,9 but not all,10 double-blind studies have shown that elderly people have better immune function and reduced infection rates when taking a multiple vitamin-mineral formula. In one double-blind trial, supplements of 100 mcg per day of selenium and 20 mg per day of zinc, with or without additional vitamin C, vitamin E, and beta-carotene, reduced infections in elderly people, though vitamins without minerals had no effect.11 Burn victims have also experienced fewer infections after receiving trace mineral supplements in double-blind research.12 These studies suggest that trace minerals may be the most important micronutrients for enhancing immunity and preventing infections in the elderly.

    Vitamin C stimulates the immune system by both elevating interferon levels13 and enhancing the activity of certain immune cells.14,15 Two studies came to opposite conclusions about the ability of vitamin C to improve immune function in the elderly,16,17 and two other studies did not agree on whether vitamin C could protect people from hepatitis.18,19 However, a review of 20 double-blind studies concluded that while several grams of vitamin C per day has only a small effect in preventing colds, when taken at the onset of a cold, it does significantly reduce the duration of a cold.20 In controlled reports studying people doing heavy exercise, cold frequency was reduced an average of 50% with vitamin C supplements ranging from 600 to 1,000 mg per day.21 Thus, the overall effect of vitamin C on immune function is unclear, and its usefulness may vary according to the situation.

    A combination of antioxidants vitamin A, vitamin C, and vitamin E significantly improved immune cell number and activity compared with placebo in a group of hospitalized elderly people.22 Daily intake of a 1,000 mg vitamin C plus 200 IU vitamin E for four months improved several measures of immune function in a preliminary study.23 To what extent immune-boosting combinations of antioxidants actually reduce the risk of infection remains unknown.

    Influenza

    Supplementing with vitamin C may reduce your flu risk.
    Influenza
    ×
     

    Dockworkers given 100 mg of vitamin C each day for ten months caught influenza 28% less often than did their coworkers not taking vitamin C. Of those who did develop the flu, the average duration of illness was 10% less in those taking vitamin C than in those not taking the vitamin.24 Other trials have reported that taking vitamin C in high amounts (2 grams every hour for 12 hours) can lead to rapid improvement of influenza infections.25,26 Such high amounts, however, should only be used under the supervision of a healthcare professional.

    Cold Sores

    Vitamin C plus flavonoids may help speed cold sore healing.
    Cold Sores
    ×
     

    Vitamin C has been shown to inactivate herpes viruses in the test tube.27 In one study, people with herpes infections received either a placebo or 200 mg of vitamin C plus 200 mg of flavonoids, each taken three to five times per day. Compared with the placebo, vitamin C and flavonoids reduced the duration of symptoms by 57%.28

    Pre- and Post-Surgery Health and Vitamin C Deficiency

    Vitamin C supports immune function and is a critical nutrient for wound healing. Supplementing with it may decrease the risk of excessive bleeding in the surgical setting.
    Pre- and Post-Surgery Health and Vitamin C Deficiency
    ×
     

    Vitamin C deficiency can be detrimental to immune function in hospitalized patients,29 and one study found that half of surgery patients recovering at home had low dietary intakes of vitamin C.30 Vitamin C is also a critical nutrient for wound healing,31,32 but studies of vitamin C supplementation have shown only minor effects on the healing of surgical wounds.33,34 Vitamin C deficiency also can increase the risk of excessive bleeding in the surgical setting.35

  • Skin Protection

    Sunburn

    Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays. Combinations of vitamin E and C offer protection against ultraviolet rays.
    Sunburn
    ×

    Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays.36 Combinations of 1,000 to 2,000 IU per day of vitamin E and 2,000 to 3,000 mg per day of vitamin C, but neither given alone, have a significant protective effect against ultraviolet rays, according to double-blind studies.37,38,39

    Oral synthetic beta-carotene alone was not found to provide effective protection when given in amounts of 15 mg per day or for only a few weeks’ time in larger amounts of 60 to 90 mg per day, but it has been effective either in very large (180 mg per day) amounts or in smaller amounts (30 mg per day) in combination with topical sunscreen.40,41,42,43,44

    Natural sources of beta-carotene or other carotenoids have been more consistently shown to protect against sunburn. One controlled study found that taking a supplement of natural carotenoids (almost all of which was beta-carotene) in daily amounts of 30 mg, 60 mg, and 90 mg gave progressively more protection against ultraviolet rays.45 In another controlled study, either 24 mg per day of natural beta-carotene or 24 mg per day of a carotenoid combination of equal amounts beta-carotene, lutein, and lycopene helped protect skin from ultraviolet rays.46 A preliminary study compared synthetic lycopene (10.1 mg per day), a natural tomato extract containing 9.8 mg of lycopene per day plus additional amounts of other carotenoids, and a solubilized tomato drink (designed to increase lycopene absorption) containing 8.2 mg of lycopene plus additional amounts of other carotenoids. After 12 weeks, only the two tomato-based products were shown to give significant protection against burning by ultraviolet light.47

    Still other trials have tested combinations of several antioxidants. One preliminary study found that a daily combination of beta-carotene (6 mg), lycopene (6 mg), vitamin E (15 IU), and selenium for seven weeks protected against ultraviolet light.48 However, a double-blind trial of a combination of smaller amounts of several carotenoids, vitamins C and E, selenium, and proanthocyanidins did not find significant UV protection compared with placebo.49 Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.50

    It should be noted that while oral protection from sunburn has been demonstrated with several types of antioxidants, the degree of protection (typically less than an SPF of 2) is much less than that provided by currently available topical sunscreens. On the other hand, these modest effects will provide some added protection to skin areas where sunscreen is also used and will give a small amount of protection to sun-exposed areas where sunscreen is not applied. However, oral protection from sunburn is not instantaneous; maximum effects are not reached until these antioxidants have been used for about eight to ten weeks.51,52

    Wound Healing

    Taking vitamin C may promote connective tissue repair.
    Wound Healing
    ×
     

    Vitamin C is needed to make collagen (connective tissue) that strengthens skin, muscles, and blood vessels and to ensure proper wound healing. Severe injury appears to increase vitamin C requirements,53 and vitamin C deficiency causes delayed healing.54 Preliminary human studies suggest that vitamin C supplementation in non-deficient people can speed healing of various types of wounds and trauma, including surgery, minor injuries, herniated intervertebral discs, and skin ulcers.54,56 A combination of 1–3 grams per day of vitamin C and 200–900 mg per day of pantothenic acid has produced minor improvements in the strength of healing skin tissue.57,58

    Sunburn

    A topically applied combination of melatonin, vitamin C, and vitamin E may boost the protection from traditional sunscreens.
    Sunburn
    ×
     

    Antioxidants have been studied as topical agents for protection against sunburn. Animal studies have found sunscreen-like effects from topical application of a vitamin C and vitamin E combination, and a controlled human study reported ultraviolet protection from the use of a lotion containing 0.02% to 0.05% of the selenium-containing amino acid known as selenomethionine.58,59 The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.60,61 A double-blind human trial tested topical vitamins C and E and melatonin, alone and in combinations, and found the highest degrees of protection from combination formulations containing 2% vitamin E, 5% vitamin C, and 1% to 2.5% melatonin.62 Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.63,64

    Sunburn

    Studies have found sunscreen-like effects from topical application of the vitamin C and vitamin E combination.
    Sunburn
    ×
     

    Antioxidants have been studied as topical agents for protection against sunburn. Animal studies have found sunscreen-like effects from topical application of a vitamin C and vitamin E combination, and a controlled human study reported ultraviolet protection from the use of a lotion containing 0.02% to 0.05% of the selenium-containing amino acid known as selenomethionine.65,66 The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.67,68 A double-blind human trial tested topical vitamins C and E and melatonin, alone and in combinations, and found the highest degrees of protection from combination formulations containing 2% vitamin E, 5% vitamin C, and 1% to 2.5% melatonin.69 Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.70,71

    Skin Ulcers

    Supplementing with vitamin C may help prevent skin ulcers and speed healing.
    Skin Ulcers
    ×

    Antioxidants such as vitamin C, vitamin E, and glutathione are depleted in healing skin tissue.72 One animal study found that vitamin E (alpha-tocopherol) applied to the skin shortened the healing time of skin ulcers.73 Another animal study reported that administration of oral vitamin E before skin lesions were introduced into the skin prevented some of the tissue damage associated with the development of pressure ulcers.74 A controlled human trial found that 400 IU of vitamin E daily improved the results of skin graft surgery for chronic venous ulcers.75 No further research has investigated the potential benefit of vitamin E for skin ulcers.

    Animal research has suggested that vitamin C may help prevent skin ulcers,76 and in a preliminary study,77 elderly patients with pressure ulcers had lower blood levels of vitamin C than did ulcer-free patients. Supplementation with vitamin C (3 grams per day) increased the speed of healing of leg ulcers in patients with a blood disorder called thalassemia, according to a double-blind study.78 And while a double-blind trial of surgical patients with pressure ulcers found that supplementation with 500 mg of vitamin C twice a day accelerated ulcer healing,79 a similar double-blind trial found no difference in the effectiveness of either 20 mg per day or 1,000 mg per day of vitamin C.80

    Eczema

    Vitamin C might be beneficial in treating eczema by affecting the immune system.
    Eczema
    ×
     

    In 1989, Medical World News reported that researchers from the University of Texas found that vitamin C, at 50–75 mg per 2.2 pounds of body weight, reduced symptoms of eczema in a double-blind trial.81 In theory, vitamin C might be beneficial in treating eczema by affecting the immune system, but further research has yet to investigate any role for this vitamin in people with eczema.

    Vitiligo

    Vitamin C has been shown to be effective at skin repigmentation in people with vitiligo.
    Vitiligo
    ×
     

    A clinical report describes the use of vitamin supplements in the treatment of vitiligo.82Folic acid and/or vitamin B12 and vitamin C levels were abnormally low in most of the 15 people studied. Supplementation with large amounts of folic acid (1–10 mg per day), along with vitamin C (1 gram per day) and intramuscular vitamin B12 injections (1,000 mcg every two weeks), produced marked repigmentation in eight people. These improvements became apparent after three months, but complete repigmentation required one to two years of continuous supplementation. In another study of people with vitiligo, oral supplementation with folic acid (10 mg per day) and vitamin B12 (2,000 mcg per day), combined with sun exposure, resulted in some repigmentation after three to six months in about half of the participants.83 This combined regimen was more effective than either vitamin supplementation or sun exposure alone.

  • Heart and Circulatory Health

    High Cholesterol

    Vitamin C appears to protect LDL cholesterol from damage, and in some trials, cholesterol levels have fallen when people supplement with vitamin C.
    High Cholesterol
    ×
    Vitamin C appears to protect LDL cholesterol from damage.84 In some clinical trials, cholesterol levels have fallen when people with elevated cholesterol supplement with vitamin C.85 Some studies report that decreases in total cholesterol occur specifically in LDL cholesterol.86 Doctors sometimes recommend 1 gram per day of vitamin C. A review of the disparate research concerning vitamin C and heart disease, however, has suggested that most protection against heart disease from vitamin C, is likely to occur with as little as 100 mg per day.87

    Capillary Fragility

    In cases of deficiency, vitamin C has been shown to increase capillary strength, in seniors and people with diabetes in particular.
    Capillary Fragility
    ×
     

    Severe vitamin C deficiency (scurvy) is a well-recognized but uncommon cause of increased capillary fragility. Whether vitamin C supplementation can help capillary fragility in people who do not have scurvy is less clear. Patients undergoing dialysis may develop low levels of vitamin C,88,89 which can lead to capillary fragility, but giving dialysis patients 50 mg of vitamin C per day had no effect on capillary fragility in one study.90 People with kidney failure and those undergoing dialysis should not supplement with more than 100 mg per day, unless supervised by a doctor.

    According to preliminary studies, vitamin C may reduce capillary weakness in diabetics, who often have low blood levels of vitamin C compared to non-diabetics.91,92 In a double-blind trial, elderly people with low vitamin C levels and capillary fragility were helped with supplementation of one gram per day of vitamin C.93

    Atherosclerosis

    Supplementing with vitamin C may help reverse the progression of atherosclerosis and protect against heart disease.
    Atherosclerosis
    ×
     

    Experimentally increasing homocysteine levels in humans has led to temporary dysfunction of the cells lining blood vessels. Researchers are concerned this dysfunction may be linked to atherosclerosis and heart disease. Vitamin C has been reported in one controlled study to reverse the dysfunction caused by increases in homocysteine.94 Vitamin C also protects LDL.95

    Despite the protective mechanisms attributed to vitamin C, some research has been unable to link vitamin C intake to protection against heart disease. These negative trials have mostly been conducted using people who consume 90 mg of vitamin C per day or more—a level beyond which further protection of LDL may not occur. Studies of people who eat foods containing lower amounts of vitamin C have been able to show a link between dietary vitamin C and protection from heart disease. Therefore, leading vitamin C researchers have begun to suggest that vitamin C may be important in preventing heart disease, but only up to 100–200 mg of intake per day.96 In a double-blind trial,97 supplementation with 250 mg of timed-release vitamin C twice daily for three years resulted in a 15% reduction in the progression of atherosclerosis, compared with placebo. Many doctors suggest that people take vitamin C—often 1 gram per day—despite the fact that research does not yet support levels higher than 500 mg per day.

    Hypertension

    Some doctors recommend that people with hypertension supplement with vitamin C, which has been found to have a blood pressure–lowering effect.
    Hypertension
    ×
    In a pooled analysis of 29 randomized controlled trials, vitamin C supplementation, as compared with placebo, resulted in statistically significant reductions in systolic (average decrease, 3.84 mm Hg) and diastolic (average decrease, 1.48 mm Hg) blood pressure. Average blood pressure reductions in the studies that included only people with hypertension were 4.85 mm Hg for systolic and 1.67 mm Hg for diastolic blood pressure.98 Thus, vitamin C when given in moderate amounts (such as 500 mg per day), has a modest blood pressure-lowering effect, both in people with high blood pressure and in those with normal blood pressure.

    Heart Attack

    Vitamin C has been reported to protect blood vessels from problems associated with heart attack risk in a variety of ways.
    Heart Attack
    ×
    Vitamin C has been reported to protect blood vessels from problems associated with heart attack risk in a variety of ways.99,100,101 However, research attempting to link vitamin C directly to protection from heart attacks has been inconsistent.102,103 The reason for this discrepancy appears related to the amount of vitamin C intake investigated in these studies. True or marginal vitamin C deficiencies do appear to increase the risk of suffering heart attacks.104,105 However, in trials comparing acceptable (i.e., non-deficient) vitamin C levels to even higher levels, additional vitamin C has not been protective.106 Therefore, though many doctors recommend that people at high risk for heart attack take vitamin C—often 1 gram per day—most evidence currently suggests that consuming as little as 100–200 mg of vitamin C per day from food or supplements may well be sufficient.

    Chronic Obstructive Pulmonary Disease

    In one study, people who got more vitamin C from their diet were less likely to be diagnosed with bronchitis, however, vitamin C has not been studied in relation to COPD.
    Chronic Obstructive Pulmonary Disease
    ×
     

    A review of nutrition and lung health reported that people with a higher dietary intake of vitamin C were less likely to be diagnosed with bronchitis.107 As yet, the effects of supplementing with vitamin C in people with COPD have not been studied.

    Heart Attack and Vitamin C Deficiency

    Taking vitamin C may reduce heart attack risk in people who are deficient.
    Heart Attack and Vitamin C Deficiency
    ×

    Vitamin C has been reported to protect blood vessels from problems associated with heart attack risk in a variety of ways.108,109,110 However, research attempting to link vitamin C directly to protection from heart attacks has been inconsistent.111,112 The reason for this discrepancy appears related to the amount of vitamin C intake investigated in these studies. True or marginal vitamin C deficiencies do appear to increase the risk of suffering heart attacks.113,114 However, in trials comparing acceptable (i.e., non-deficient) vitamin C levels to even higher levels, additional vitamin C has not been protective.115 Therefore, though many doctors recommend that people at high risk for heart attack take vitamin C—often 1 gram per day—most evidence currently suggests that consuming as little as 100–200 mg of vitamin C per day from food or supplements may well be sufficient.

  • Pain Management

    Wound Healing

    Taking vitamin C may promote connective tissue repair.
    Wound Healing
    ×
     

    Vitamin C is needed to make collagen (connective tissue) that strengthens skin, muscles, and blood vessels and to ensure proper wound healing. Severe injury appears to increase vitamin C requirements,116 and vitamin C deficiency causes delayed healing.117 Preliminary human studies suggest that vitamin C supplementation in non-deficient people can speed healing of various types of wounds and trauma, including surgery, minor injuries, herniated intervertebral discs, and skin ulcers.117,119 A combination of 1–3 grams per day of vitamin C and 200–900 mg per day of pantothenic acid has produced minor improvements in the strength of healing skin tissue.120,121

    Bruising

    Vitamin C supplements have been shown to reduce bruising in people with low vitamin C intake.
    Bruising
    ×

    Doctors often suggest that people who experience easy bruising supplement with 100 mg to 3 grams of vitamin C per day for several months. Controlled research is limited, but vitamin C supplements have been shown to reduce bruising in people with low vitamin C intake.121Flavonoids are often recommended along with vitamin C. Flavonoids are vitamin-like substances that can help strengthen capillaries and therefore may also help with bruising.122 Flavonoids may also increase the effectiveness of vitamin C; citrus flavonoids, in particular, improve the absorption of vitamin C. Older preliminary research suggested that vitamin C, 400–800 mg per day, in combination with 400–800 mg per day of the flavonoid, hesperidin, reduced bruising in menopausal women.123 A small, preliminary trial in Germany gave three people with progressive pigmented purpura (a chronic bruising disorder) 1,000 mg per day of vitamin C and 100 mg per day of the flavonoid rutoside. After four weeks, noticeable bruising was no longer apparent and did not recur in the three month period after treatment was stopped.124 Controlled research is needed to better establish whether vitamin C and flavonoids are effective for easy bruising.

     

    Sprains and Strains

    Vitamin C is needed to make collagen, the “glue” that strengthens connective tissue. Vitamin C supplementation can speed healing of various types of trauma.
    Sprains and Strains
    ×
     

    Antioxidant supplements, including vitamin C and vitamin E, may help prevent exercise-related muscle injuries by neutralizing free radicals produced during strenuous activities.125 Controlled research, some of it double-blind, has shown that 400–3,000 mg per day of vitamin C may reduce pain and speed up muscle strength recovery after intense exercise.126,127 Reductions in blood indicators of muscle damage and free radical activity have also been reported for supplementation with 400–1,200 IU per day of vitamin E in most studies,128,129,130 but no measurable benefits in exercise recovery have been reported.131 A combination of 90 mg per day of coenzyme Q10 and a very small amount of vitamin E did not produce any protective effects in one double-blind trial.132

    Vitamin C is needed to make collagen, the “glue” that strengthens connective tissue. Injury, at least when severe, appears to increase vitamin C requirements,133 and vitamin C deficiency causes delayed healing from injury.134 Preliminary human studies have suggested that vitamin C supplementation in non-deficient people can speed healing of various types of trauma, including musculoskeletal injuries,134,136 but double-blind research has not confirmed these effects for athletic injuries, which included sprains and strains.137

    Low Back Pain

    A preliminary report suggested that vitamin C helped many people avoid surgery for their disc-related low back pain.
    Low Back Pain
    ×
     

    A preliminary report in 1964 suggested that 500–1,000 mg per day of vitamin C helped many people avoid surgery for their disc-related low back pain.137 No controlled research has been done to examine this claim further.

  • Oral Health

    Gingivitis

    If you are deficient in vitamin C, supplementing with this vitamin may improve your overall gum health.
    Gingivitis
    ×
      

    People who are deficient in vitamin C may be at increased risk for periodontal disease.138 When a group of people with periodontitis who normally consumed only 20–35 mg of vitamin C per day were given an additional 70 mg per day, objective improvement of periodontal tissue occurred in only six weeks.139 It makes sense for people who have a low vitamin C intake (e.g., people who eat few fruits and vegetables) to supplement with vitamin C in order to improve gingival health.

    Cold Sores

    Vitamin C plus flavonoids may help speed cold sore healing.
    Cold Sores
    ×
     

    Vitamin C has been shown to inactivate herpes viruses in the test tube.140 In one study, people with herpes infections received either a placebo or 200 mg of vitamin C plus 200 mg of flavonoids, each taken three to five times per day. Compared with the placebo, vitamin C and flavonoids reduced the duration of symptoms by 57%.141

    Gingivitis

    In one study, supplementing with vitamin C plus flavonoids improved gum health in a group of people with gingivitis.
    Gingivitis
    ×
     

    People who are deficient in vitamin C may be at increased risk for periodontal disease.142 When a group of people with periodontitis who normally consumed only 20–35 mg of vitamin C per day were given an additional 70 mg per day, objective improvement of periodontal tissue occurred in only six weeks.143 It makes sense for people who have a low vitamin C intake (e.g., people who eat few fruits and vegetables) to supplement with vitamin C in order to improve gingival health.

    For people who consume adequate amounts of vitamin C in their diet, several studies have found that supplemental vitamin C has no additional therapeutic effect. Research,144 including double-blind evidence,145 shows that vitamin C fails to significantly reduce gingival inflammation in people who are not vitamin C deficient. In one study, administration of vitamin C plus flavonoids (300 mg per day of each) did improve gingival health in a group of people with gingivitis;146 there was less improvement, however, when vitamin C was given without flavonoids. Preliminary evidence has suggested that flavonoids by themselves may reduce inflammation of the gums.147

  • Stress and Mood Management

    Stress

    Studies have shown that supplementing with vitamin C helps to normalize stress-hormone levels.
    Stress
    ×
     

    Animal studies suggest that supplementing with vitamin C can reduce blood levels of stress-related hormones and other measures of stress.148,149,150,151 Controlled studies of athletes have shown that vitamin C supplementation (1,000 to 1,500 mg per day) can reduce stress hormone levels after intense exercise.152,153 Surgery patients given 2,000 mg per day of vitamin C during the week before and after surgery had a more rapid return to normal of several stress-related hormones compared with patients not given vitamin C.154 In a double-blind trial, young adults took 3,000 mg per day of vitamin C for two weeks, then were given a psychological stress test involving public speaking and mental arithmetic.155 Compared with a placebo group, those taking vitamin C rated themselves less stressed, scored better on an anxiety questionnaire, had smaller elevations of blood pressure, and returned sooner to lower levels of an adrenal stress hormone following the stress test.

    Depression

    In a double-blind study, the combination of vitamin C and an antidepressant drug (fluoxetine) was significantly more effective than the antidepressant alone.
    Depression
    ×
    In a double-blind study of Egyptian children with depression, the combination of vitamin C (500 mg twice a day) and an antidepressant drug (fluoxetine) was significantly more effective than fluoxetine alone.156
  • Women's Health

    Dysmenorrhea

    Supplementing with a combination of vitamin B3, vitamin C, and the flavonoid rutin resulted in a 90% effectiveness for relieving menstrual cramps in one study.
    Dysmenorrhea
    ×
    The niacin form of vitamin B3 has been reported to be effective in relieving menstrual cramps in 87% of a group of women taking 200 mg of niacin per day throughout the menstrual cycle.157 They then took 100 mg every two or three hours while experiencing menstrual cramps.158 In a follow-up study, this protocol was combined with 300 mg of vitamin C and 60 mg of the flavonoid rutin per day, which resulted in a 90% effectiveness for relieving menstrual cramps. Since these two preliminary studies were published many years ago, no further research has explored the relationship between niacin and dysmenorrhea. Niacin may not be effective unless taken for seven to ten days before the onset of menstrual flow.

    Pregnancy and Postpartum Support

    Supplementing with vitamin C during pregnancy may reduce the risk of premature rupture of membranes (PROM) and may improve lung function in the child.
    Pregnancy and Postpartum Support
    ×
     

    Premature rupture of membranes (PROM) affects 10 to 20% of all pregnancies. It is an important cause of preterm delivery and is associated with increased rates of complications in both the mother and child. In a double-blind study, supplementing with 100 mg of vitamin C per day, beginning in the twentieth week of pregnancy, reduced the incidence of PROM by 74%.159 The women in this study were consuming only about 65 mg of vitamin C per day in their diet, which is less than the RDA of 80 to 85 mg per day for pregnant women. In a double-blind study of pregnant smokers, supplementation with 500 mg per day of vitamin C, beginning at 23 weeks of pregnancy or earlier and continuing until delivery, improved lung function and decreased the incidence of wheezing in the offspring.160

    Endometriosis

    A combination of vitamin C and vitamin E can help lessen the pain of endometriosis.
    Endometriosis
    ×
    In a double-blind study of women with pelvic pain presumed to be due to endometriosis, supplementation with vitamin E (1,200 IU per day) and vitamin C (1,000 mg per day) for eight weeks resulted in an improvement of pain in 43% of women, whereas none of the women receiving a placebo reported pain relief.161

    Female Infertility and Luteal Phase Defect

    Vitamin C has been shown to improve fertility in woman with a uterine condition known as luteal phase defect.
    Female Infertility and Luteal Phase Defect
    ×
     

    In some women, infertility is due to a hormonal abnormality known as luteal phase defect. In this condition, the uterine lining does not develop and mature properly, presumably because of a deficiency of the hormone progesterone. In a study of infertile women with luteal phase defect, supplementation with 750 mg of vitamin C per day for up to six months resulted in a pregnancy rate of 25%, compared with a rate of 11% in an untreated control group, a statistically significant difference.162

    Menopause

    A combination of vitamin C and the flavonoid hesperidin were reported to relieve hot flashes in menopausal women.
    Menopause
    ×
     

    In 1964, a preliminary trial reported that 1,200 mg each of vitamin C and the flavonoid hesperidin taken over the course of the day helped relieve hot flashes.163 Although placebo effects are strong in women with hot flashes, other treatments used in that trial failed to act as effectively as the flavonoid/vitamin C combination. Since then, researchers have not explored the effects of flavonoids or vitamin C in women with menopausal symptoms.

    Menorrhagia

    Vitamin C protects capillaries (small blood vessels) from damage. In so doing, it might protect against the blood loss of menorrhagia.
    Menorrhagia
    ×
     

    Both vitamin C and flavonoids protect capillaries (small blood vessels) from damage. In so doing, they might protect against the blood loss of menorrhagia. In one small study, 88% of women with menorrhagia improved when given 200 mg vitamin C and 200 mg flavonoids three times per day.164 In another study, 70% of women with excessive menstrual bleeding experienced at least a 50% reduction in bleeding after taking a flavonoid product.165 The preparation used in this study contained 90% diosmin and 10% hesperidin and was given in the amount of 1,000 mg per day, beginning five days prior to the expected start of menstruation and continuing until the end of bleeding for three cycles.

  • Eye Health Support

    Glaucoma

    Supplementing with vitamin C may help reduce intraocular pressure.
    Glaucoma
    ×
     

    Several studies have shown that supplementing with vitamin C can significantly reduce elevated intraocular pressure in individuals with glaucoma.166 These studies used at least 2 grams per day of vitamin C; much larger amounts were sometimes given. Higher quantities of vitamin C appeared to be more effective than smaller amounts.

    Doctors often suggest that people with glaucoma take vitamin C to “bowel tolerance.”167 The bowel-tolerance level is determined by progressively increasing vitamin C intake until loose stools or abdominal pain occurs, and then reducing the amount slightly, to a level that does not cause these symptoms. The bowel tolerance level varies considerably from person to person, usually ranging from about 5 to 20 or more grams per day. Vitamin C does not cure glaucoma and must be used continually to maintain a reduction in intraocular pressure.

    Macular Degeneration

    Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration. Vitamin C protects against oxidative damage and may reduce macular degeneration risk.
    Macular Degeneration
    ×

    Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration.168 Because vitamin C functions as an antioxidant, it has the potential to protect against macular degeneration. However, in a double-blind trial, supplementing with 500 mg of vitamin C daily for eight years did not decrease the incidence of macular degeneration in healthy male physicians.169

    Cataracts

    Supplementing with vitamin C, an important nutrient for healthy vision, has been linked with lower risk of developing cataracts.
    Cataracts
    ×

    People with low blood levels of antioxidants and those who eat few antioxidant-rich fruits and vegetables have been reported to be at high risk for cataracts.170,171

    The major antioxidants in the lens of the eye are vitamin C172 and glutathione (a molecule composed of three amino acids).173 Vitamin C is needed to activate vitamin E,174 which in turn activates glutathione. Both nutrients are important for healthy vision. People who take multivitamins or any supplements containing vitamins C or E for more than 10 years have been reported to have a 60% lower risk of forming a cataract.175

    Vitamin C levels in the eye decrease with age.176 However, supplementing with vitamin C prevents this decrease172 and has been linked to a lower risk of developing cataracts.170,179 Healthy people are more likely to take vitamin C and vitamin E supplements than those with cataracts according to some,180 but not all,181 studies. Dietary vitamin C intake has not been consistently associated with protection from cataracts.182,183 Nonetheless, because people who supplement with vitamin C have developed far fewer cataracts in some research,184,185 doctors often recommend 500 to 1,000 mg of vitamin C supplementation as part of a cataract prevention program. The difference between successful and unsuccessful trials may be tied to the length of time people actually supplement with vitamin C. In one preliminary study, people taking vitamin C for at least ten years showed a dramatic reduction in cataract risk, but those taking vitamin C for less than ten years showed no evidence of protection at all.186

  • Blood Sugar and Diabetes Support

    Type 2 Diabetes

    Supplementing with vitamin C may lower blood glucose levels and protect cardiovascular health.
    Type 2 Diabetes
    ×

    Vitamin C, at a dose of 500 mg twice per day, was found to reduce fasting blood glucose levels, although not HbA1c, after four months in a placebo-controlled trial.185 A meta-analysis of other controlled trials found vitamin C supplementation can reduce blood glucose levels (but not HbA1c) in people with type 2 diabetes, and is especially effective in those who are older and those who have taken vitamin C for 30 days or more.186

    Through its anti-inflammatory and antioxidant effects, vitamin C has been shown to lower blood pressure and improve cardiovascular health in people with type 2 diabetes.187 In addition, like other antioxidants, vitamin C reduces formation of advanced glycation end-products (AGEs), which cause widespread damage to proteins and DNA.188 Antioxidants like vitamins C and E protect against damage to micro-vessels and therefore have the potential to help prevent type 2 diabetes complications such as retinopathy, nephropathy, and neuropathy.189,190 Furthermore, low vitamin C levels in blood and in the eye have been correlated with increased risk of retinopathy.191,192 In a pilot study, a combination supplement with vitamin C and other antioxidant vitamins, minerals, and plant extracts improved vision in subjects with type 2 diabetes and early stage retinopathy.193

    High-dose vitamin C supplementation has been reported to interfere with some devices for self-monitoring of blood glucose levels. This can raise the risk of overtreatment leading to hypoglycemia.194 Therefore it is important that people with type 2 diabetes who rely on self-monitoring glucose devices talk with their healthcare provider before starting a vitamin C supplement.

    Pancreatic Insufficiency

    Taking antioxidant supplements, such as vitamin C, may lessen pain and prevent pancreatitis recurrences.
    Pancreatic Insufficiency
    ×
    There are few controlled trials of antioxidant supplementation to patients with pancreatitis. One small controlled study of acute pancreatitis patients found that sodium selenite at a dose of 50 micrograms (mcg) daily resulted in decreased levels of a marker of free radical activity, and no patient deaths occurred.195 In a small double-blind trial including recurrent acute and chronic pancreatitis patients, supplements providing daily doses of 600 mcg selenium, 9,000 IU beta-carotene, 540 mg vitamin C, 270 IU vitamin E, and 2,000 mg methionine significantly reduced pain, normalized several blood measure of antioxidant levels and free radical activity, and prevented acute recurrences of pancreatitis.196 These researches later reported that continuing antioxidant treatment in these patients for up to five years or more significantly reduced the total number of days spent in the hospital and resulted in 78% of patients becoming pain-free and 88% returning to work.197

    Type 1 Diabetes

    Supplementing with vitamin C may benefit people with type 1 diabetes by preventing free radical damage and protecting blood vessels.
    Type 1 Diabetes
    ×
    Vitamin C is important for lowering oxidative stress and preventing oxidative tissue damage linked to high glucose levels in people with diabetes. Vitamin C levels have been found to be lower in people with type 1 diabetes compared to healthy people, and low levels have been correlated with markers of decreased cardiovascular health in those with type 1 diabetes.198,199 In addition, because vitamin C uptake by cells is enhanced by insulin and suppressed by high glucose levels, people with type 1 diabetes have more difficulty meeting their cellular and tissue needs for vitamin C.200 In a placebo-controlled trial, 1,000 mg vitamin C along with 800 IU vitamin E per day for six months improved blood vessel function in participants with type 1 diabetes.201 Another placebo-controlled trial found the high dose of 6 grams of vitamin C per day for six months improved markers of capillary health.202 Several studies show vitamin C may protect blood vessels from free radical damage during the vulnerable periods of high blood glucose in subjects with type 1 diabetes.203,204,205,206 A small one-month study in children with type 1 diabetes found no effect of supplementation with 250 mg per day of vitamin C on vascular health. Another trial in nine type 1 diabetes-affected adolescents investigated doses of vitamin C ranging from 250–750 mg per day, depending on weight, combined with vitamin E for six weeks and saw no change in vascular function. Whether these negative findings reflect study factors such as low dose, short duration, and small number of participants is unclear.207,208

    Hypoglycemia

    Vitamin C helps control blood sugar levels in people with diabetes, and since there are similarities in the way the body regulates high and low blood sugar levels, it might be helpful for hypoglycemia as well.
    Hypoglycemia
    ×
      

    Research has shown that supplementing with chromium (200 mcg per day)209 or magnesium (340 mg per day)210 can prevent blood sugar levels from falling excessively in people with hypoglycemia. Niacinamide (vitamin B3) has also been found to be helpful for hypoglycemic people.211 Other nutrients, including vitamin C, vitamin E, zinc, copper, manganese, and vitamin B6, may help control blood sugar levels in diabetics.212 Since there are similarities in the way the body regulates high and low blood sugar levels, these nutrients might be helpful for hypoglycemia as well, although the amounts needed for that purpose are not known.

    Type 1 Diabetes and Diabetic Retinopathy

    Antioxidant nutrients including selenium, vitamin A, vitamin C, and vitamin E may combat free radicals associated with diabetic retinopathy.
    Type 1 Diabetes and Diabetic Retinopathy
    ×
    Because oxidation damage is believed to play a role in the development of diabetic eye damage (retinopathy), antioxidant nutrients might be protective. One doctor has administered a daily regimen of 500 mcg selenium, 800 IU vitamin E, 10,000 IU vitamin A, and 1,000 mg vitamin C for several years to 20 people with diabetic eye damage (retinopathy). During that time, 19 of the 20 people showed either improvement or no progression of their retinopathy.213 People who wish to supplement with more than 250 mcg of selenium per day should consult a healthcare practitioner.
  • Menstrual and PMS Support

    Dysmenorrhea

    Supplementing with a combination of vitamin B3, vitamin C, and the flavonoid rutin resulted in a 90% effectiveness for relieving menstrual cramps in one study.
    Dysmenorrhea
    ×
    The niacin form of vitamin B3 has been reported to be effective in relieving menstrual cramps in 87% of a group of women taking 200 mg of niacin per day throughout the menstrual cycle.214 They then took 100 mg every two or three hours while experiencing menstrual cramps.215 In a follow-up study, this protocol was combined with 300 mg of vitamin C and 60 mg of the flavonoid rutin per day, which resulted in a 90% effectiveness for relieving menstrual cramps. Since these two preliminary studies were published many years ago, no further research has explored the relationship between niacin and dysmenorrhea. Niacin may not be effective unless taken for seven to ten days before the onset of menstrual flow.

    Endometriosis

    A combination of vitamin C and vitamin E can help lessen the pain of endometriosis.
    Endometriosis
    ×
    In a double-blind study of women with pelvic pain presumed to be due to endometriosis, supplementation with vitamin E (1,200 IU per day) and vitamin C (1,000 mg per day) for eight weeks resulted in an improvement of pain in 43% of women, whereas none of the women receiving a placebo reported pain relief.216

    Menorrhagia

    Vitamin C protects capillaries (small blood vessels) from damage. In so doing, it might protect against the blood loss of menorrhagia.
    Menorrhagia
    ×
     

    Both vitamin C and flavonoids protect capillaries (small blood vessels) from damage. In so doing, they might protect against the blood loss of menorrhagia. In one small study, 88% of women with menorrhagia improved when given 200 mg vitamin C and 200 mg flavonoids three times per day.217 In another study, 70% of women with excessive menstrual bleeding experienced at least a 50% reduction in bleeding after taking a flavonoid product.218 The preparation used in this study contained 90% diosmin and 10% hesperidin and was given in the amount of 1,000 mg per day, beginning five days prior to the expected start of menstruation and continuing until the end of bleeding for three cycles.

  • Allergy and Lung Support

    Asthma

    Supplementing with vitamin C reduces the tendency of the bronchial passages to go into spasm, an action that has been confirmed in double-blind research.
    Asthma
    ×
     

    Supplementation with 1 gram of vitamin C per day reduces the tendency of the bronchial passages to go into spasm,219 an action that has been confirmed in double-blind research.220 Beneficial effects of short-term vitamin C supplementation (i.e., less than three days) have been observed. In double-blind trials, supplementation with 1,000 to 1,500 mg of vitamin C per day for 2 to 14 days prevented attacks of exercise-induced asthma.221,222 Two other preliminary trials found that vitamin C supplementation reduced bronchial reactivity to metacholine, a drug that causes bronchial constriction.223,224 However, other studies,225 including two double-blind trials,226,227 have failed to corroborate these findings. The only double-blind trial of a long duration found that vitamin C supplementation (1 gram per day for 14 weeks) reduced the severity and frequency of attacks among Nigerian adults with asthma.228 A buffered form of vitamin C (such as sodium ascorbate or calcium ascorbate) may work better for some asthmatics than regular vitamin C (ascorbic acid).229

    Hay Fever

    Vitamin C has antihistamine activity, and supplementing with it has been reported to help people with hay fever.
    Hay Fever
    ×
     

    Although vitamin C has antihistamine activity, and supplementation, in preliminary research,230,231 has been reported to help people with hay fever, 2,000 mg of vitamin C per day did not reduce hay fever symptoms in a placebo controlled trial.232 Thus, while some doctors recommend that hay fever sufferers take 1,000–3,000 mg of vitamin C per day, supportive evidence remains weak.

    Hives

    High amounts of vitamin C might help people with hives by lowering histamine levels.
    Hives
    ×
     

    In theory, high amounts of vitamin C might help people with hives by lowering histamine levels.233 Amounts of at least 2,000 mg daily appear necessary to produce these effects.233 No research trials have yet explored the clinical effects of vitamin C supplementation in people with hives.

    Asthma

    There is some evidence that a combination of antioxidants vitamin E, vitamin C, and selenium may help prevent asthma thought to be caused by air pollution.
    Asthma
    ×

    There is some evidence that combinations of antioxidants such as vitamin E, vitamin C, and selenium may help improve symptoms of asthma throught to be caused by air pollution.234 In one double-blind study, 46 Dutch bicyclists were randomly assigned to receive a placebo or 100 mg of vitamin E and 500 mg of vitamin C daily for 15 weeks.235 Lung function was measured before and after each training session on 380 different occasions, and ambient ozone concentrations were measured during each training session. After analysis, researchers concluded that bicyclists with the vitamins C and E blunted the adverse effects of ozone on measures of lung function. In another double-blind study, 17 adults (18 to 39 years old) were randomly assigned to receive either 400 IU per day of vitamin E and 500 mg per day of vitamin C or a placebo for five weeks.236 Tests showing improved measures of lung function led researchers to conclude that supplementation with vitamins C and E inhibited the decline in pulmonary function induced in asthmatics by exposure to air pollutants. Also using a double-blind design, another study of 158 children with asthma living in Mexico City were randomly assigned to receive, a daily supplement containing 50 mg of vitamin E and 250 mg of vitamin C or a placebo.237 Tests results suggested that supplementing with vitamins C and E may reduce the adverse effect of ozone exposure on lung function of children with moderate to severe asthma.

  • Digestive Support

    Gastritis

    Vitamin C may reduce free radical damage in the stomach lining in the case of gastritis caused by the bacteriaH. pylori.
    Gastritis
    ×
     

    When H. pylori causes gastritis, free radical levels rise in the stomach lining.238 These unstable molecules contribute to inflammation and damage to the stomach lining. Vitamin C, an antioxidant that helps quench free radical molecules, is low in the stomach juice of people with chronic gastritis. This deficiency may be the link between chronic gastritis and the increased risk of stomach cancer. When people with gastritis took 500 mg of vitamin C twice a day, vitamin C levels in their gastric juice rose, though not to normal levels.239 In another trial, vitamin C supplementation (5 grams per day divided into several doses for four weeks) appeared to eliminate H. pylori infection.240 While no direct evidence proves that taking vitamin C reduces gastritis symptoms, scientists widely believe that any agent capable of knocking out H. pylori should help people with this condition.

    Peptic Ulcer

    Vitamin C may be useful in treating peptic ulcers because of its ability to help eradicate H. pylori
    Peptic Ulcer
    ×

    Little is known about the effects of vitamin C supplementation for people with peptic ulcer. People with gastritis, a related condition, have been found to have low levels of vitamin C in their stomach juice. Vitamin C may also help eradicate H. pylori in people with gastritis. Vitamin C may one day prove to have a therapeutic effect for people with peptic ulcer; however, further research in this area is needed.241

    Gallstones

    Vitamin C is needed for the body to convert cholesterol to bile acids and may help reduce symptoms of gallstones.
    Gallstones
    ×

    Vitamin C is needed to convert cholesterol to bile acids. In theory, such a conversion should reduce gallstone risks. Women who have higher blood levels of vitamin C have a reduced risk of gallstones.242 Although this does not prove that vitamin C supplements can prevent or treat gallstones, some researchers believe this is plausible.243 One study reported that people who drink alcohol and take vitamin C supplements have only half the risk of gallstones compared with other drinkers, though the apparent protective effect of vitamin C did not appear in non-drinkers.244 In another trial, supplementation with vitamin C (500 mg taken four times per day for two weeks before gallbladder surgery) led to improvement in one parameter of gallstone risk (“nucleation time”), though there was no change in the relative level of cholesterol found in bile.245 While many doctors recommend vitamin C supplementation to people with a history of gallstones, supportive evidence remains preliminary.

    Morning Sickness

    Vitamin K and vitamin C, taken together, may provide relief of morning sickness symptoms for some women.
    Morning Sickness
    ×
     

    Vitamin K and vitamin C, taken together, may provide relief of symptoms for some women. In one study, 91% of women who took 5 mg of vitamin K and 25 mg of vitamin C per day reported the complete disappearance of morning sickness within three days.246 Menadione was removed from the market a number of years ago because of concerns about potential toxicity. Although some doctors still use a combination of vitamin K1 (the most prevalent form of vitamin K in food) and vitamin C for morning sickness, no studies on this treatment have been done.

  • Joint Health

    Gout

    Supplementing with vitamin C might reduce the risk of gout attacks, as it appears to help reduce uric acid levels.
    Gout
    ×
     

    In one small study, people who took 4 grams of vitamin C (but not lower amounts) had an increase in urinary excretion of uric acid within a few hours, and those who took 8 grams of vitamin C per day for several days had a reduction in serum uric acid levels.247 Thus, supplemental vitamin C could, in theory, reduce the risk of gout attacks. However, the authors of this study warned that taking large amounts of vitamin C could also trigger an acute attack of gout by abruptly changing uric acid levels in the body. Another study showed that taking lower amounts of vitamin C (500 mg per day) for two months significantly reduced blood levels of uric acid, especially in people whose initial uric acid levels were elevated.248 For people with a history of gout attacks, it seems reasonable to begin vitamin C supplementation at 500 mg per day, and to increase the amount gradually if uric acid levels do not decrease.

    Low Back Pain

    A preliminary report suggested that vitamin C helped many people avoid surgery for their disc-related low back pain.
    Low Back Pain
    ×
     

    A preliminary report in 1964 suggested that 500–1,000 mg per day of vitamin C helped many people avoid surgery for their disc-related low back pain.249 No controlled research has been done to examine this claim further.

  • Kidney and Urinary Tract Health

    Urinary Tract Infection

    Supplementing with vitamin C may treat acute UTIs and help people who are prone to recurrent UTIs.
    Urinary Tract Infection
    ×
     

    Many doctors recommend 5,000 mg or more of vitamin C per day for an acute UTI, as well as long-term supplementation for people who are prone to recurrent UTIs. Vitamin C has been shown to inhibit the growth of E. coli, the most common bacterial cause of UTIs.250 In addition, supplementation with 4,000 mg or more of vitamin C per day, results in a slight increase in the acidity of the urine,251 creating an “unfriendly” environment for some infection-causing bacteria. In one controlled trial, pregnant women who supplemented with 100 mg of vitamin C per day experienced 56% less UTI frequency, compared with a placebo.252

  • Healthy Pregnancy and New Baby

    Pregnancy and Postpartum Support

    Supplementing with vitamin C during pregnancy may reduce the risk of premature rupture of membranes (PROM) and may improve lung function in the child.
    Pregnancy and Postpartum Support
    ×
     

    Premature rupture of membranes (PROM) affects 10 to 20% of all pregnancies. It is an important cause of preterm delivery and is associated with increased rates of complications in both the mother and child. In a double-blind study, supplementing with 100 mg of vitamin C per day, beginning in the twentieth week of pregnancy, reduced the incidence of PROM by 74%.253 The women in this study were consuming only about 65 mg of vitamin C per day in their diet, which is less than the RDA of 80 to 85 mg per day for pregnant women. In a double-blind study of pregnant smokers, supplementation with 500 mg per day of vitamin C, beginning at 23 weeks of pregnancy or earlier and continuing until delivery, improved lung function and decreased the incidence of wheezing in the offspring.254

  • Children's Health

    Autism

    In one trial, autistic children given vitamin C had less severe symptoms than those taking placebo, possibly because vitamin C affects a hormone pathway typically disturbed in children with autism.
    Autism
    ×

    In one double-blind trial lasting ten weeks, autistic children given 1 gram vitamin C per day for each 20 pounds of body weight showed a reduction in symptom severity compared with placebo.255 The authors speculate that vitamin C may play a positive role because of its known effects on a hormone pathway typically disturbed in children with autism.

    Childhood Diseases

    Vitamin C enhances the immune system and may protect against viral infections, including measles and chicken pox.
    Childhood Diseases
    ×
     

    Vitamin C has been demonstrated in test tube, animal, and human studies to have immune-enhancing and direct antiviral properties.256 Preliminary observations made on the effect of vitamin C on viral infections have involved both measles and chicken pox.257 An active immune system uses vitamin C rapidly, and blood levels fall in children with bacterial or viral infections.258 Reduced immune cell activity has been observed in people with measles, but in one preliminary study, supplementation with 250 mg daily of vitamin C in children 18 months to 3 years old had no impact on the course of the illness.259 The authors of this study admit that this amount of vitamin C may have been too low to bring about an observable increase in immune cell activity and thus an increase in speed of recovery.

    Ear Infections

    Supplementing with vitamin C stimulates the immune system and may help prevent ear infections.
    Ear Infections
    ×
     

    Vitamin C supplementation has been reported to stimulate immune function.260,261 As a result, some doctors recommend between 500 mg and 1,000 mg of vitamin C per day for people with ear infections. Nonetheless, vitamin C supplementation has not been studied by itself in people with ear infections.

  • Healthy Aging/Senior Health

    Macular Degeneration

    Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration. Vitamin C protects against oxidative damage and may reduce macular degeneration risk.
    Macular Degeneration
    ×

    Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration.262 Because vitamin C functions as an antioxidant, it has the potential to protect against macular degeneration. However, in a double-blind trial, supplementing with 500 mg of vitamin C daily for eight years did not decrease the incidence of macular degeneration in healthy male physicians.263

    Age-Related Cognitive Decline

    Use of vitamin C, alone or with vitamin E, has been associated with better cognitive function and a reduced risk of certain forms of dementia (not including Alzheimer’s disease).
    Age-Related Cognitive Decline
    ×

    Use of vitamin C or vitamin E supplements, or both, has been associated with better cognitive function and a reduced risk of certain forms of dementia (not including Alzheimer’s disease).264 Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.

     
  • Menopause Support

    Menopause

    A combination of vitamin C and the flavonoid hesperidin were reported to relieve hot flashes in menopausal women.
    Menopause
    ×
     

    In 1964, a preliminary trial reported that 1,200 mg each of vitamin C and the flavonoid hesperidin taken over the course of the day helped relieve hot flashes.265 Although placebo effects are strong in women with hot flashes, other treatments used in that trial failed to act as effectively as the flavonoid/vitamin C combination. Since then, researchers have not explored the effects of flavonoids or vitamin C in women with menopausal symptoms.

  • Ear Health Support

    Ear Infections

    Supplementing with vitamin C stimulates the immune system and may help prevent ear infections.
    Ear Infections
    ×
     

    Vitamin C supplementation has been reported to stimulate immune function.266,267 As a result, some doctors recommend between 500 mg and 1,000 mg of vitamin C per day for people with ear infections. Nonetheless, vitamin C supplementation has not been studied by itself in people with ear infections.

  • Brain Health

    Schizophrenia

    People with schizophrenia may require more vitamin C than the general population. In one trial, vitamin C reduced hallucinations, suspiciousness, and disorganized thoughts.
    Schizophrenia
    ×
     

    Up to 6 grams daily of vitamin C has been reported to be beneficial for people with schizophrenia;268,269 in one case the addition of 400 IU daily of vitamin E enhanced this benefit.269 A small preliminary trial using 8 grams daily of vitamin C showed decreases in hallucinations, suspiciousness, and unusual and disorganized thoughts in 77% of schizophrenic patients.271 In all reported cases, patients were also being treated with sychiatric medications. Some early studies found no difference between blood and urine vitamin C levels in schizophrenics and non-schizophrenics, either before or after supplementation.272,273,274 However, later studies found that blood and urine levels of vitamin C were lower in schizophrenics than in non-schizophrenics before and after a single 1,000 mg “load” of vitamin C was taken. After four weeks of daily supplementation with 1,000 mg of vitamin C, blood levels became the same, but urinary levels remained lower in the schizophrenic group, leading the researchers to conclude that the amount of vitamin C required by people with schizophrenia may be greater than that of the general population.275,276

    Age-Related Cognitive Decline

    Use of vitamin C, alone or with vitamin E, has been associated with better cognitive function and a reduced risk of certain forms of dementia (not including Alzheimer’s disease).
    Age-Related Cognitive Decline
    ×

    Use of vitamin C or vitamin E supplements, or both, has been associated with better cognitive function and a reduced risk of certain forms of dementia (not including Alzheimer’s disease).276 Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.

     

    Bipolar Disorder

    Vitamin C helps the body reduce its load of vanadium, a mineral that adversely influences bipolar disorder. It has improved symptoms of depression and mania in some studies.
    Bipolar Disorder
    ×
     

    Vitamin C helps the body to reduce its load of vanadium and this has been studied for its possible role in treatment of bipolar disorder.277 A double-blind trial found that both manic and depressed bipolar patients were significantly improved after one-time administration of 3 grams of vitamin C, compared with a placebo.278 The same study found that both manic and depressed patients did better on a reduced-vanadium diet compared to a normal diet. Another double-blind study reported that 4 grams per day of vitamin C in combination with a drug known as EDTA (which also helps remove elements such as vanadium from the body) was helpful to depressed bipolar patients but not to those experiencing mania.279 Until more is known, people with bipolar illness should avoid supplements containing vanadium and consider supplementing with vitamin C.

  • Fitness

    Athletic Performance and Reducing Pain and Speeding Muscle Strength Recovery after Intense Exercise

    Taking vitamin C for several days before and after intense exercise may reduce pain and speed muscle strength recovery.
    Athletic Performance and Reducing Pain and Speeding Muscle Strength Recovery after Intense Exercise
    ×

    Most research has demonstrated that strenuous exercise increases production of harmful substances called free radicals, which can damage muscle tissue and result in inflammation and muscle soreness. Exercising in cities or smoggy areas also increases exposure to free radicals. Antioxidants, including vitamin C and vitamin E, neutralize free radicals before they can damage the body, so antioxidants may aid in exercise recovery. Regular exercise increases the efficiency of the antioxidant defense system, potentially reducing the amount of supplemental antioxidants that might otherwise be needed for protection. However, at least theoretically, supplements of antioxidant vitamins may be beneficial for older or untrained people or athletes who are undertaking an especially vigorous training protocol or athletic event.280,281

    Placebo-controlled research, some of it double-blind, has shown that taking 400 to 3,000 mg of vitamin C per day for several days before and after intense exercise may reduce pain and speed up muscle strength recovery.282,283,284 However, taking vitamin C only after such exercise was not effective in another double-blind study.285 While some research has reported that vitamin E supplementation in the amount of 800 to 1,200 IU per day reduces biochemical measures of free radical activity and muscle damage caused by strenuous exercise,286,287,288 several studies have not found such benefits,289,290,291,292 and no research has investigated the effect of vitamin E on performance-related measures of strenuous exercise recovery. A combination of 90 mg per day of coenzyme Q10 and a very small amount of vitamin E did not produce any protective effects for marathon runners in one double-blind trial,293 while in another double-blind trial a combination of 50 mg per day of zinc and 3 mg per day of copper significantly reduced evidence of post-exercise free radical activity.294

    In most well-controlled studies, exercise performance has not been shown to improve following supplementation with vitamin C, unless a deficiency exists, as might occur in athletes with unhealthy or irrational eating patterns.295,296 Similarly, vitamin E has not benefited exercise performance, 297,298 except possibly at high altitudes. 299,300

    Athletic Performance and Vitamin C Deficiency

    Antioxidants, including vitamin C, neutralize exercise-related free radicals before they can damage the body, so antioxidants may aid in exercise recovery. Especially in cases of vitamin C deficiency, supplementing with the vitamin may improve exercise performance.
    Athletic Performance and Vitamin C Deficiency
    ×

    Most research has demonstrated that strenuous exercise increases production of harmful substances called free radicals, which can damage muscle tissue and result in inflammation and muscle soreness. Exercising in cities or smoggy areas also increases exposure to free radicals. Antioxidants, including vitamin C and vitamin E, neutralize free radicals before they can damage the body, so antioxidants may aid in exercise recovery. Regular exercise increases the efficiency of the antioxidant defense system, potentially reducing the amount of supplemental antioxidants that might otherwise be needed for protection. However, at least theoretically, supplements of antioxidant vitamins may be beneficial for older or untrained people or athletes who are undertaking an especially vigorous training protocol or athletic event.301,302

    Placebo-controlled research, some of it double-blind, has shown that taking 400 to 3,000 mg of vitamin C per day for several days before and after intense exercise may reduce pain and speed up muscle strength recovery.303,304,305 However, taking vitamin C only after such exercise was not effective in another double-blind study.306 While some research has reported that vitamin E supplementation in the amount of 800 to 1,200 IU per day reduces biochemical measures of free radical activity and muscle damage caused by strenuous exercise,307,308,309 several studies have not found such benefits,310,311,312,313 and no research has investigated the effect of vitamin E on performance-related measures of strenuous exercise recovery. A combination of 90 mg per day of coenzyme Q10 and a very small amount of vitamin E did not produce any protective effects for marathon runners in one double-blind trial,314 while in another double-blind trial a combination of 50 mg per day of zinc and 3 mg per day of copper significantly reduced evidence of post-exercise free radical activity.315

    In most well-controlled studies, exercise performance has not been shown to improve following supplementation with vitamin C, unless a deficiency exists, as might occur in athletes with unhealthy or irrational eating patterns.316,317,318 Similarly, vitamin E has not benefited exercise performance, 319,320 except possibly at high altitudes. 321,322

  • Recovery

    Athletic Performance and Reducing Pain and Speeding Muscle Strength Recovery after Intense Exercise

    Taking vitamin C for several days before and after intense exercise may reduce pain and speed muscle strength recovery.
    Athletic Performance and Reducing Pain and Speeding Muscle Strength Recovery after Intense Exercise
    ×

    Most research has demonstrated that strenuous exercise increases production of harmful substances called free radicals, which can damage muscle tissue and result in inflammation and muscle soreness. Exercising in cities or smoggy areas also increases exposure to free radicals. Antioxidants, including vitamin C and vitamin E, neutralize free radicals before they can damage the body, so antioxidants may aid in exercise recovery. Regular exercise increases the efficiency of the antioxidant defense system, potentially reducing the amount of supplemental antioxidants that might otherwise be needed for protection. However, at least theoretically, supplements of antioxidant vitamins may be beneficial for older or untrained people or athletes who are undertaking an especially vigorous training protocol or athletic event.323,324

    Placebo-controlled research, some of it double-blind, has shown that taking 400 to 3,000 mg of vitamin C per day for several days before and after intense exercise may reduce pain and speed up muscle strength recovery.325,326,327 However, taking vitamin C only after such exercise was not effective in another double-blind study.328 While some research has reported that vitamin E supplementation in the amount of 800 to 1,200 IU per day reduces biochemical measures of free radical activity and muscle damage caused by strenuous exercise,329,330,331 several studies have not found such benefits,332,333,334,335 and no research has investigated the effect of vitamin E on performance-related measures of strenuous exercise recovery. A combination of 90 mg per day of coenzyme Q10 and a very small amount of vitamin E did not produce any protective effects for marathon runners in one double-blind trial,336 while in another double-blind trial a combination of 50 mg per day of zinc and 3 mg per day of copper significantly reduced evidence of post-exercise free radical activity.337

    In most well-controlled studies, exercise performance has not been shown to improve following supplementation with vitamin C, unless a deficiency exists, as might occur in athletes with unhealthy or irrational eating patterns.338,339 Similarly, vitamin E has not benefited exercise performance, 340,341 except possibly at high altitudes. 342,343

  • Men's Health

    Male Infertility and Sperm Agglutination

    Vitamin C protects sperm from oxidative damage and keeps sperm from sticking together.
    Male Infertility and Sperm Agglutination
    ×

    Vitamin C protects sperm from oxidative damage.344 Supplementing vitamin C improves the quality of sperm in smokers.345 When sperm stick together (a condition called agglutination), fertility is reduced. Vitamin C reduces sperm agglutination,346 and supplementation with 200–1,000 mg per day increased the fertility of men with this condition in a controlled study.347,348 Many doctors recommend 1 gram of vitamin C per day for infertile men, particularly those diagnosed with sperm agglutination. However, a double-blind trial studying the effects of combined vitamin C and vitamin E supplementation found no improvements in semen quality among men with low sperm motility.349

What Are Star Ratings?
×
Reliable and relatively consistent scientific data showing a substantial health benefit.
Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

Temp Title
×
Temp Text

References

1. Hemilä H. Does vitamin C alleviate the symptoms of the common cold?—a review of current evidence. Scand J Infect Dis 1994;26:1-6.

2. Hemilä H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hypotheses 1999;52:171-8.

3. Geber WF, Lefkowitz SS, Hung CY. Effect of ascorbic acid, sodium salicylate, and caffeine on the serum interferon level in response to viral infection. Pharmacology 1975;13:228-33.

4. Hemila H. Vitamin C and the common cold. Br J Nutr 1992;67:3-16.

5. Hunt C, Chakravorty NK, Annan G, et al. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res 1994;64:212–9.

6. Hemilä H. Does vitamin C alleviate the symptoms of the common cold?—a review of current evidence. Scand J Infect Dis 1994;26:1-6.

7. Menzel DB. Antioxidant vitamins and prevention of lung disease.Ann N Y Acad Sci 1992;669:141-55.

8. Pike J, Chandra RK. Effect of vitamin and trace element supplementation on immune indices in healthy elderly. Int J Vitam Nutr Res 1995;65:117-21.

9. Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 1992;340:1124-7.

10. Chavance M, Herbeth B, Lemoine A, et al. Does multivitamin supplementation prevent infections in healthy elderly subjects? A controlled trial.Int.J Vitam Nutr Res 1993;63:11-6.

11. Girodon F, Lombard M, Galan P, et al. Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Ann Nutr Metab 1997;41:98-107.

12. Berger MM, Spertini F, Shenkin A, et al. Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial. Am J Clin Nutr 1998;68:365-71.

13. Geber WF, Lefkowitz SS, Hung CY. Effect of ascorbic acid, sodium salicylate, and caffeine on the serum interferon level in response to viral infection. Pharmacology 1975;13:228-33.

14. Anderson R. The immunostimulatory, anti-inflammatory an anti-allergic properties of ascorbate. Adv Nutr Res 1984;6:19-45 [review].

15. Banic S. Immunostimulation by vitamin C. Int J Vitam Nutr Res Suppl 1982;23:49-52 [review].

16. Delafuente JC, Prendergast JM, Modigh A. Immunologic modulation by vitamin C in the elderly. Int J Immunopharmacol 1986;8:205-11.

17. Kennes B, Dumont I, Brohee D, et al. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerontology 1983;29:305-10.

18. Murata A. Virucidal activity of vitamin C for prevention and treatment of viral diseases. In Proceedings of the First Intersectional Congress of IAMS, vol 3. Science Council Japan, 1975, 432.

19. Knodell RG, Tate MA, Akl BF, Wilson JW. Vitamin C prophylaxis for post transfusion hepatitis: lack of effect in a controlled trial. Am J Clin Nutr 1981;34:20-3.

20. Hemila H. Vitamin C and the common cold. Br J Nutr 1992;67:3-16.

21. Hemilä H. Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress. Int J Sports Med 1996;17:379-83.

22. Penn ND, Purkins L, Kelleher J, et al. The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial. Age Ageing 1991;20:169-74.

23. de la Fuente M, Ferrandez MD, Burgos MS, et al. Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol 1998;76:373-80.

24. Renker K, Wegner S. Vitamin C-Prophylaxe in der Volkswertf Stralsund. Deutsche Gesundheitswesen 1954;9:702-6.

25. Klenner FR. The treatment of poliomyelitis and other virus diseases with vitamin C. South Med Surg 1949;111:210-4.

26. Pauling L. Vitamin C, the Common Cold and the Flu. San Francisco: W. H. Freeman & Company, 1976 [review].

27. Holden M, Molloy E. Further experiments on the inactivation of herpes virus by vitamin C (l-ascorbic acid). J Immunol 1937;33:251-7.

28. Terezhalmy GT, Bottomley WK, Pelleu GB. The use of water-soluble bioflavonoid-ascorbic acid complex in the treatment of recurrent herpes labialis. Oral Surg 1978;45:56-62.

29. Dowd PS, Kelleher J, Walker BE, Guillou PJ. Nutrition and cellular immunity in hospital patients. Br J Nutr 1986;55:515-27.

30. Stotts NA, Whitney JD. Nutritional intake and status of clients in the home with open surgical wounds. J Community Health Nurs 1990;7:77-86.

31. Thomas DR. Specific nutritional factors in wound healing. Adv Wound Care 1997;10:40-3 [review].

32. Wendt MD, Soparkar CN, Louie K, et al. Ascorbate stimulates type I and type III collagen in human Tenon's fibroblasts. J Glaucoma 1997;6:402-7.

33. Vaxman F, Olender S, Lambert A, et al. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial. Eur Surg Res 1995;27:158-66.

34. Vaxman F, Olender S, Lambert A, et al. Can the wound healing process be improved by vitamin supplementation? Experimental study on humans. Eur Surg Res 1996;28:306-14.

35. Blee TH, Cogbill TH, Lambert PJ. Hemorrhage associated with vitamin C deficiency in surgical patients. Surgery 2002;131:408-12.

36. Fuchs J. Potentials and limitations of the natural antioxidants RRR-alpha-tocopherol, L-ascorbic acid and beta-carotene in cutaneous photoprotection. Free Radic Biol Med 1998;25:848-73 [review].

37. Werninghaus K, Meydani M, Bhawan J, et al. Evaluation of the photoprotective effect of oral vitamin E supplementation. Arch Dermatol 1994;130:1257-61.

38. Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med 1998;25:1006-12.

39. Eberlein-Konig B, Placzek M, Przybilla B. Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E). J Am Acad Dermatol 1998;38:45-8.

40. McArdle F, Rhodes LE, Parslew RA, et al. Effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced oxidative stress in human skin. Am J Clin Nutr 2004;80:1270-5.

41. Garmyn M, Ribaya-Mercado JD, Russel RM, et al. Effect of beta-carotene supplementation on the human sunburn reaction. Exp Dermatol 1995;4:104-11.

42. Wolf C, Steiner A, Honigsmann H, et al. Do oral carotenoids protect human skin against UV erythema, psoralen phototoxicity, and UV-induced DNA damage? J Invest Dermatol 1988;90:55-57.

43. Mathews-Roth MM, Pathak MA, Parrish J, et al. A clinical trial of the effects of oral beta-carotene on the responses of human skin to solar radiation. J Invest Dermatol 1972;59:349-53.

44. Gollnick HP, Hopfenmuller W, Hemmes C, et al. Systemic B-carotene plus topical sunscreen are an optimal protection against harmful effects of natural UV-sunlight. Eur J Dermatol 1996;6:200-5.

45. Lee J, Jiang S, Levine N, Watson RR. Carotenoid supplementation reduces erythema in human skin after simulated solar radiation exposure. Proc Soc Exp Biol Med 2000;223:170-4.

46. Heinrich U, Gartner C, Wiebusch M, et al. Supplementation with beta-carotene or a similar amount of mixed carotenoids protects humans from UV-induced erythema. J Nutr 2003;133:98-101.

47. Aust O, Stahl W, Sies H, et al. Supplementation with tomato-based products increases lycopene, phytofluene, and phytoene levels in human serum and protects against UV-light-induced erythema. Int J Vitam Nutr Res 2005;75:54-60.

48. Cesarini JP, Michel L, Maurette JM, et al. Immediate effects of UV radiation on the skin: modification by an antioxidant complex containing carotenoids. Photodermatol Photoimmunol Photomed 2003;19:182-9.

49. Greul AK, Grundmann JU, Heinrich F, et al. Photoprotection of UV-irradiated human skin: an antioxidative combination of vitamins E and C, carotenoids, selenium and proanthocyanidins. Skin Pharmacol Appl Skin Physiol 2002;15:307-15.

50. La Ruche G, Cesarini JP. Protective effect of oral selenium plus copper associated with vitamin complex on sunburn cell formation in human skin. Photodermatol Photoimmunol Photomed 1991;8:232-5.

51. Sies H, Stahl W. Nutritional protection against skin damage from sunlight. Annu Rev Nutr 2004;24:173-200 [review].

52. Sies H, Stahl W. Carotenoids and UV protection. Photochem Photobiol Sci 2004;3:749-52 [review].

53. Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med 1986;314:892-902 [review].

54. Mazzotta MY. Nutrition and wound healing. J Am Podiatr Med Assoc 1994;84:456-62 [review].

55. Ringsdorf WM Jr, Cheraskin E. Vitamin C and human wound healing. Oral Surg Oral Med Oral Pathol 1982;53:231-6 [review].

56. Vaxman F, Olender S, Lambert A, et al. Can the wound healing process be improved by vitamin supplementation? Experimental study on humans. Eur Surg Res 1996;28:306-14.

57. Vaxman F, Olender S, Lambert A, et al. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial. Eur Surg Res 1995;27:158-66.

58. Lin JY, Selim MA, Shea CR, et al. UV photoprotection by combination topical antioxidants vitamin C and vitamin E. J Am Acad Dermatol 2003;48:866-74.

59. Burke KE, Burford RG, Combs GF Jr, et al. The effect of topical L-selenomethionine on minimal erythema dose of ultraviolet irradiation in humans. Photodermatol Photoimmunol Photomed 1992;9:52-7.

60. Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). Influence of the application time point. Dermatology 1997;195:248-52.

61. Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). A dose response study. Arch Dermatol Res 1996;288:522-6.

62. Dreher F, Gabard B, Schwindt DA, Maibach HI. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema: a human study in vivo. Br J Dermatol 1998;139:332-9.

63. Dreher F, Denig N, Gabard B, et al. Effect of topical antioxidants on UV-induced erythema formation when administered after exposure. Dermatology 1999;198:52-5.

64. Fuchs J. Potentials and limitations of the natural antioxidants RRR-alpha-tocopherol, L-ascorbic acid and beta-carotene in cutaneous photoprotection. Free Radic Biol Med 1998;25:848-73 [review].

65. Lin JY, Selim MA, Shea CR, et al. UV photoprotection by combination topical antioxidants vitamin C and vitamin E. J Am Acad Dermatol 2003;48:866-74.

66. Burke KE, Burford RG, Combs GF Jr, et al. The effect of topical L-selenomethionine on minimal erythema dose of ultraviolet irradiation in humans. Photodermatol Photoimmunol Photomed 1992;9:52-7.

67. Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). Influence of the application time point. Dermatology 1997;195:248-52.

68. Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). A dose response study. Arch Dermatol Res 1996;288:522-6.

69. Dreher F, Gabard B, Schwindt DA, Maibach HI. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema: a human study in vivo. Br J Dermatol 1998;139:332-9.

70. Dreher F, Denig N, Gabard B, et al. Effect of topical antioxidants on UV-induced erythema formation when administered after exposure. Dermatology 1999;198:52-5.

71. Fuchs J. Potentials and limitations of the natural antioxidants RRR-alpha-tocopherol, L-ascorbic acid and beta-carotene in cutaneous photoprotection. Free Radic Biol Med 1998;25:848-73 [review].

72. Houwing R, Overgoor M, Kon M, et al. Pressure-induced skin lesions in pigs: reperfusion injury and the effects of vitamin E. J Wound Care 2000; 9:36-40.

73. Lucero MJ, Vigo J, Rabasco AM, et al. Protection by alpha-tocopherol against skin necrosis induced by doxorubicin hydrochloride. Pharmazie 1993;48:772-5.

74. Shukla A, Rasik AM, Patnaik GK. Depletion of reduced glutathione, ascorbic acid, vitamin E, and antioxidant defence enzymes in a healing cutaneous wound. Free Radic Res 1997;26:93-101.

75. Ramasastry, SS, Angel MF, Narayanan K, et al. Biochemical evidence of lipoperoxidation in venous stasis ulcer: Beneficial role of vitamin E as antioxidant. Ann NY Acad Sci 1989; 506-8.

76. Hajarizadeh H, Lebredo L, Barrie R, Woltering EA. Protective effect of doxorubicin in vitamin C or dimethyl sulfoxide against skin ulceration in the pig. Ann Surg Oncol 1994;1:411-4.

77. Goode HF, Burns E, Walker BE. Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture. BMJ 1992;305:935-7.

78. Afifi AM, Ellis L, Huntsman RG, Said MI. High dose ascorbic acid in the management of thalassaemia leg ulcers—a pilot study. Br J Dermatol 1975;92:339-41.

79. Taylor TV, Rimmer S, Day B, et al. Ascorbic acid supplementation in the treatment of pressure cores. Lancet 1974;ii:544-6.

80. ter Riet G, Kessels AG, Knipschild PG. Randomized clinical trial of ascorbic acid in the treatment of pressure ulcers. J Clin Epidemiol 1995;48:1453-60.

81. Anonymous. Severe atopic dermatitis responds to ascorbic acid. Med World News 1989;April 24:41.

82. Montes LF, Diaz ML, Lajous J, Garcia NJ. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis 1992;50:39-42.

83. Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol 1997;77:460-2.

84. Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991;54:1113S-8S.

85. Simon JA. Vitamin C and cardiovascular disease: a review. J Am Coll Nutr 1992;11:107-27.

86. Gatto LM, Hallen GK, Brown AJ, Samman S. Ascorbic acid induces a favorable lipoprotein profile in women. J Am Coll Nutr 1996;15;154-8.

87. Balz F. Antioxidant Vitamins and Heart Disease. Presented at the 60th Annual Biology Colloquium, Oregon State University, February 25, 1999.

88. Bradley DW, Maynard JE, Webster H. Plasma and whole blood concentrations of ascorbic acid in patients undergoing long-term hemodialysis. Am J Clin Pathol 1973;60:145-7.

89. Sullivan JF, Eisenstein AB. Ascorbic acid depletion during hemodialysis. JAMA 1972;220:1697-9.

90. Tomson CR, Channon SM, Parkinson IS. Correction of subclinical ascorbate deficiency in patients receiving dialysis: effects on plasma oxalate, serum cholesterol, and capillary fragility. Clin Chim Acta 1989;180:255-64.

91. Cox BD, Butterfield WJ. Vitamin C supplements and diabetic cutaneous capillary fragility. Br Med J 1975;3:205.

92. Will JC, Byers T. Does diabetes mellitus increase the requirement for vitamin C? Nutr Rev 1996;54:193-202 [review].

93. Schorah CJ, Tormey WP, Brooks GH, et al. The effect of vitamin C supplements on body weight, serum proteins, and general health of an elderly population. Am J Clin Nutr 1981;34:871-6.

94. Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia. An effect reversible with vitamin C therapy. Circulation 1999;99:1156-60.

95. Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991;54:1113S-8S.

96. Balz F. Antioxidant Vitamins and Heart Disease. Presented at the 60th Annual Biology Colloquium, Oregon State University, February 25, 1999.

97. Salonen JT, Nyyssönen K, Salonen R, et al. Antioxidant supplementation in atherosclerosis prevention (ASAP) study: a randomized trial of the effect of vitamin E and C on 3-year progression of carotid atherosclerosis. J Intern Med 2000;248:177-86.

98. Juraschek SP, Guallar E, Appel LJ, Miller ER III. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2012;95:1079-88.

99. Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia. An effect reversible with vitamin C therapy. Circulation 1999;99:1156-60.

100. Fuller CJ, Grundy SM, Norkus EP, Jialal I. Effect of ascorbate supplementation on low density lipoprotein oxidation in smokers. Atherosclerosis 1996;119:139-50.

101. Rath M, Pauling L. Solution to the puzzle of human cardiovascular disease: Its primary cause is ascorbate deficiency leading to the deposition of lipoprotein (a) and fibrinogen/fibrin in the vascular wall. J Orthomol Med 1992;6:125-34.

102. Manson JE, Stampfer MJ, Willett WC, et al. A prospective study of vitamin C and incidence of coronary heart disease in women. Circulation 1992;85:865 [abstract].

103. Klipstein-Grobusch K, Geleijnse JM, den Breeijen JH, et al. Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr 1999;69:261-6.

104. Nyyssönen K, Parvianinen MT, Salonen R, et al. Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ 1997;314:634-8.

105. Simon JA, Hudes ES, Browner WS. Serum ascorbic acid and cardiovascular disease prevalence in U.S. adults. Epidemiology 1998;9:316-21.

106. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450-6.

107. Sridhar MK. Nutrition and lung health. BMJ 1995;310:75-6.

108. Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia. An effect reversible with vitamin C therapy. Circulation 1999;99:1156-60.

109. Fuller CJ, Grundy SM, Norkus EP, Jialal I. Effect of ascorbate supplementation on low density lipoprotein oxidation in smokers. Atherosclerosis 1996;119:139-50.

110. Rath M, Pauling L. Solution to the puzzle of human cardiovascular disease: Its primary cause is ascorbate deficiency leading to the deposition of lipoprotein (a) and fibrinogen/fibrin in the vascular wall. J Orthomol Med 1992;6:125-34.

111. Manson JE, Stampfer MJ, Willett WC, et al. A prospective study of vitamin C and incidence of coronary heart disease in women. Circulation 1992;85:865 [abstract].

112. Klipstein-Grobusch K, Geleijnse JM, den Breeijen JH, et al. Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr 1999;69:261-6.

113. Nyyssönen K, Parvianinen MT, Salonen R, et al. Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ 1997;314:634-8.

114. Simon JA, Hudes ES, Browner WS. Serum ascorbic acid and cardiovascular disease prevalence in U.S. adults. Epidemiology 1998;9:316-21.

115. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450-6.

116. Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med 1986;314:892-902 [review].

117. Mazzotta MY. Nutrition and wound healing. J Am Podiatr Med Assoc 1994;84:456-62 [review].

118. Ringsdorf WM Jr, Cheraskin E. Vitamin C and human wound healing. Oral Surg Oral Med Oral Pathol 1982;53:231-6 [review].

119. Vaxman F, Olender S, Lambert A, et al. Can the wound healing process be improved by vitamin supplementation? Experimental study on humans. Eur Surg Res 1996;28:306-14.

120. Vaxman F, Olender S, Lambert A, et al. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial. Eur Surg Res 1995;27:158-66.

121. Schorah CJ, Tormey WP, Brooks GH, et al. The effect of vitamin C supplements on body weight, serum proteins, and general health of an elderly population. Am J Clin Nutr 1981;34:871-6.

122. Shamrai EF. Vitamin P. Its chemical nature and mechanism of physiologic action. Uspekhi Sovremennoi Biologii 1968;65:186-201.

123. Horoschak A. Nocturnal leg cramps, easy bruisability and epistaxis in menopausal patients: treated with hesperidin and ascorbic acid. Delaware State Med J 1959;Jan:19-22.

124. Reinhold U, Seiter S, Ugurel S, Tilgen W. Treatment of progressive pigmented purpura with oral bioflavonoids and ascorbic acid: an open pilot study in 3 patients. J Am Acad Dermatol 1999;41:207-8.

125. Kanter M. Free radicals, exercise and antioxidant supplementation. Proc Nutr Soc 1998;57:9-13 [review].

126. Jakeman P, Maxwell S. Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise. Eur J Appl Physiol 1993;67:426-30.

127. Kaminski M, Boal R. An effect of ascorbic acid on delayed-onset muscle soreness. Pain 1992;50:317-21.

128. McBride JM, Kraemer WJ, Triplett-McBride T, Sebastianelli W. Effect of resistance exercise on free radical production. Med Sci Sports Exerc 1998;30:67-72.

129. Rokitzki L, Logemann E, Huber G, et al. alpha-Tocopherol supplementation in racing cyclists during extreme endurance training. Int J Sport Nutr 1994;4:253-64.

130. Meydani M, Evans WJ, Handelman, et al. Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults. Am J Physiol 1993;264(5 pt 2):R992-8.

131. Tiidus PM, Houston ME. Vitamin E status and response to exercise training. Sports Med 1995;20:12-23 [review].

132. Kaikkonen J, Kosonen L, Nyyssonen K, et al. Effect of combined coenzyme Q10 and d-alpha-tocopheryl acetate supplementation on exercise-induced lipid peroxidation and muscular damage: a placebo-controlled double-blind study in marathon runners. Free Radic Res 1998;29:85-92.

133. Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med 1986;314:892-902 [review].

134. Mazzotta MY. Nutrition and wound healing. J Am Podiatr Med Assoc 1994;84:456-62 [review].

135. Ringsdorf WM Jr, Cheraskin E. Vitamin C and human wound healing. Oral Surg Oral Med Oral Pathol 1982;53:231-6 [review].

136. Gey GO, Cooper KH, Bottenberg RA. Effect of ascorbic acid on endurance performance and athletic injury. JAMA 1970;211:105.

137. Greenwood J. Optimum vitamin C intake as a factor in the preservation of disc integrity. Med Ann District of Columbia 1964;33:274-6.

138. Vaananen MK, Markkanen HA, Tuovinen VJ, et al. Periodontal health related to plasma ascorbic acid. Proc Finn Dent Soc 1993;89:51-9.

139. Aurer-Kozelj J, Kralj-Klobucar N, Buzina R, Bacic M. The effect of ascorbic acid supplementation on periodontal tissue ultrastructure in subjects with progressive periodontitis. Int J Vitam Nutr Res 1982;52:333-41.

140. Holden M, Molloy E. Further experiments on the inactivation of herpes virus by vitamin C (l-ascorbic acid). J Immunol 1937;33:251-7.

141. Terezhalmy GT, Bottomley WK, Pelleu GB. The use of water-soluble bioflavonoid-ascorbic acid complex in the treatment of recurrent herpes labialis. Oral Surg 1978;45:56-62.

142. Vaananen MK, Markkanen HA, Tuovinen VJ, et al. Periodontal health related to plasma ascorbic acid. Proc Finn Dent Soc 1993;89:51-9.

143. Aurer-Kozelj J, Kralj-Klobucar N, Buzina R, Bacic M. The effect of ascorbic acid supplementation on periodontal tissue ultrastructure in subjects with progressive periodontitis. Int J Vitam Nutr Res 1982;52:333-41.

144. Woolfe SN, Kenney EB, Hume WR, Carranza FA Jr. Relationship of ascorbic acid levels of blood and gingival tissue with response to periodontal therapy. J Clin Periodontol 1984;11:159-65.

145. Vogel RI, Lamster IB, Wechsler SA, et al. The effects of megadoses of ascorbic acid on PMN chemotaxis and experimental gingivitis. J Periodontol 1986;57:472-9.

146. El-Ashiry GM, Ringsdorf WM, Cheraskin E. Local and systemic influences in periodontal disease. II. Effect of prophylaxis and natural versus synthetic vitamin C upon gingivitis. J Periodontol 1964;35:250-9.

147. Carvel I, Halperin V. Therapeutic effect of water soluble bioflavonoids in gingival inflammatory conditions. Oral Surg Oral Med Oral Pathol 1961;14:847-55.

148. Pardue SL, Thaxton JP, Brake J. Role of ascorbic acid in chicks exposed to high environmental temperature. J Appl Physiol 1985;58:1511-6.

149. Doulas NL, Constantopoulos A, Litsios B. Effect of ascorbic acid on guinea pig adrenal adenylate cyclase activity and plasma cortisol. J Nutr1987;117:1108-14.

150. Zhou X, Xie M, Niu C, Sun R. The effects of dietary vitamin C on growth, liver vitamin C and serum cortisol in stressed and unstressed juvenile soft-shelled turtles (Pelodiscus sinensis). Comp Biochem Physiol A Mol Integr Physiol 2003;135:263-70.

151. Satterlee DG, Aguilera-Quintana I, Munn BJ, Krautmann BA. Vitamin C amelioration of the adrenal stress response in broiler chickens being prepared for slaughter. Comp Biochem Physiol A 1989;94:569-74.

152. Peters EM, Anderson R, Nieman DC, et al. Vitamin C supplementation attenuates the increases in circulating cortisol, adrenaline and anti-inflammatory polypeptides following ultramarathon running. Int J Sports Med 2001;22:537-43.

153. Peters EM, Anderson R, Theron AJ. Attenuation of increase in circulating cortisol and enhancement of the acute phase protein response in vitamin C-supplemented ultramarathoners. Int J Sports Med 2001;22:120-6.

154. Gromova EG, Sviridova SP, Kushlinskii NE, et al. Regulation of the indices of neuroendocrine status in surgical patients with lung cancer using optimal doses of ascorbic acid. Anesteziol Reanimatol1990;5:71-4 [in Russian].

155. Brody S, Preut R, Schommer K, Schurmeyer TH. A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress. Psychopharmacology (Berl) 2002;159:319-24.

156. Amr M, El-Mogy A, Shams T, et al. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J 2013;12:31.

157. Hudgins AP. Am Practice Digest Treat 1952;3:892-3.

158. Hudgins AP. Vitamins P, C and niacin for dysmenorrhea therapy. West J Surg 1954;Dec:610-1.

159. Casanueva E, Ripoll C, Tolentino M, et al. Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial. Am J Clin Nutr 2005;81:859-63.

160. McEvoy CT, Schilling D, Clay N, et al. Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial. JAMA 2014;311:2074–82.

161. Santanam N, Kavtaradze N, Murphy A, et al. Antioxidant supplementation reduces endometriosis-related pelvic pain in humans. Transl Res 2013;161:189-95.

162. Henmi H, Endo T, Kitajima Y, et al. Effects of ascorbic acid supplementation on serum progesterone levels in patients with a luteal phase defect. Fertil Steril 2003;80:459-61.

163. CJ Smith. Non-hormonal control of vaso-motor flushing in menopausal patients. Chicago Med 1964;67:193-5.

164. Cohen JD, Rubin HW. Functional menorrhagia: treatment with bioflavonoids and vitamin C. Curr Ther ResClin Exp 1960;2:539-42.

165. Mukherjee GG, Gajaraj AJ, Mathias J, Marya D. Treatment of abnormal uterine bleeding with micronized flavonoids. Int J Gynaecol Obstet2005;89:156-7.

166. Ringsdorf WM Jr, Cheraskin E. Ascorbic acid and glaucoma: a review. J Holistic Med 1981;3:167-72.

167. Boyd HH. Eye pressure lowering effect of vitamin C. J Orthomolec Med 1995;10:165-8.

168. Young RW. Solar radiation and age-related macular degeneration. Surv Ophthalmol 1988:32:252-69.

169. Christen WG, Glynn RJ, Sesso HD, et al. Vitamins E and C and medical record-confirmed age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 2012;119:1642-9.

170. Jacques PF, Chylack LT Jr. Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention. Am J Clin Nutr 1991;53:352S-5S.

171. Knekt P, Heliovaara M, Rissanen A, et al. Serum antioxidant vitamins and risk of cataract. BMJ 1992;305:1392-4.

172. Taylor A, Jacques PF, Nadler D, et al. Relationship in humans between ascorbic acid consumption and levels of total and reduce ascorbic acid in lens, aqueous humor, and plasma. Curr Eye Res 1991;10:751-9.

173. Reddy VN. Glutathione and its function in the lens—an overview. Exp Eye Res 1990;150:771-8.

174. Packer JE, Slater TF, Wilson RL. Direct observation of a free radical interaction between vitamin E and vitamin C. Nature 1979;278:737-8.

175. Mares-Perlman JA, Lyle BJ, Klein R, et al. Vitamin supplement use and incident cataracts in a population-based study. Arch Ophthalmol 2000;118:1556-63.

176. Taylor A. Cataract: relationship between nutrition and oxidation. J Am Coll Nutr 1993;12:138-46 [review].

177. Jacques PF, Chylack LT, McGandy RB, Hartz SC. Antioxidant status in persons with and without senile cataract. Arch Ophthalmol 1988;106:337-40.

178. Robertson JMD, Donner AP, Trevithick JR. Vitamin E intake and risk of cataracts in humans. Ann NY Acad Sci 1989;570:372-82.

179. Seddon JM, Christen WG, Manson JE, et al. The use of vitamin supplements and the risk of cataract among US male physicians. Am J Public Health 1994;84:788-92.

180. Lyle BJ, Mares-Perlman JA, Klein BE, et al. Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am J Epidemiol 1999;149:801-9.

181. Chasan-Taber L, Willett WC, Seddon JM, et al. A prospective study of vitamin supplement intake and cataract extraction among U.S. women. Epidemiology 1999;10:679-84.

182. Robertson J McD, Donner AP, Trevithick JR. A possible role for vitamins C and E in cataract prevention. Am J Clin Nutr 1991;53:346S-51S.

183. Hankinson SE, Stampfer MJ, Seddon JM, et al. Nutrient intake and cataract extraction in women: a prospective study. Br Med J 1992;305(6849):335-9.

184. Jacques PF, Taylor A, Hankinson SE, et al. Long-term vitamin C supplement use and prevalence of early age-related lens opacities. Am J Clin Nutr 1997;66:911-6.

185. Mason S, Rasmussen B, van Loon L, et al. Ascorbic acid supplementation improves postprandial glycaemic control and blood pressure in individuals with type 2 diabetes: Findings of a randomized cross-over trial. Diabetes Obes Metab 2019;21:674–82.

186. Ashor A, Werner A, Lara J, et al. Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr 2017;71:1371–80.

187. Das U. Vitamin C for Type 2 Diabetes Mellitus and Hypertension. Arch Med Res 2019;50:11–4.

188. Franke S, Muller L, Santos M, et al. Vitamin C intake reduces the cytotoxicity associated with hyperglycemia in prediabetes and type 2 diabetes. Biomed Res Int 2013;2013:896536.

189. Rahimi-Madiseh M, Malekpour-Tehrani A, Bahmani M, Rafieian-Kopaei M. The research and development on the antioxidants in prevention of diabetic complications. Asian Pac J Trop Med 2016;9:825–31.

190. May J. Ascorbic acid repletion: A possible therapy for diabetic macular edema? Free Radic Biol Med 2016;94:47–54.

191. Kundu D, Mandal T, Nandi M, et al. Oxidative stress in diabetic patients with retinopathy. Ann Afr Med 2014;13:41–6.

192. Park S, Ghim W, Oh S, et al. Association of vitreous vitamin C depletion with diabetic macular ischemia in proliferative diabetic retinopathy. PLoS One 2019;14:e0218433.

193. Moshetova L, Vorob'eva I, Alekseev I, Mikhaleva L. Results of the use of antioxidant and angioprotective agents in type 2 diabetes patients with diabetic retinopathy and age-related macular degeneration. Vestn Oftalmol. 2015;131:34–44. [in Russian]

194. Cho J, Ahn S, Yim J, et al. Influence of Vitamin C and Maltose on the Accuracy of Three Models of Glucose Meters. Ann Lab Med 2016;36:271–4.

195. Kulinski B, Buchner M, Schweder R, Nagel R. Acute pancreatitis—a free radical disease. Decrease in fatality with sodium selenite (Na2SeO3) therapy. Z Gesamte Inn Med 1991;46:145-9 [in German].

196. Uden S, Bilton D, Nathan L, et al. Antioxidant therapy for recurrent pancreatitis: placebo-controlled trial. Aliment Pharmacol Ther 1990;4:357-71.

197. McCloy R. Chronic pancreatitis at Manchester, UK. Focus on antioxidant therapy. Digestion 1998;59(suppl 4):36-48 [review].

198. Fatima N, Faisal S, Zubair S, et al. Role of Pro-Inflammatory Cytokines and Biochemical Markers in the Pathogenesis of Type 1 Diabetes: Correlation with Age and Glycemic Condition in Diabetic Human Subjects. PLoS One 2016;11:e0161548.

199. Odermarsky M, Lykkesfeldt J, Liuba P. Poor vitamin C status is associated with increased carotid intima-media thickness, decreased microvascular function, and delayed myocardial repolarization in young patients with type 1 diabetes. Am J Clin Nutr 2009;90:447–52.

200. Cunningham J. The glucose/insulin system and vitamin C: implications in insulin-dependent diabetes mellitus. J Am Coll Nutr 1998;17:105–8.

201. Beckman J, Goldfine A, Gordon M, et al. Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol 2003;285:H2392–8.

202. Juhl B, Klein F, Christiansen J. Vitamin C treatment reduces transcapillary escape rate of albumin in type 1 diabetes. Eur J Intern Med 2004;15:428–35.

203. Ceriello A, Novials A, Ortega E, et al. Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes. Diabetes 2012;61:2993–7.

204. Ceriello A, Novials A, Ortega E, et al. Vitamin C further improves the protective effect of GLP-1 on the ischemia-reperfusion-like effect induced by hyperglycemia post-hypoglycemia in type 1 diabetes. Cardiovasc Diabetol 2013;12:97.

205. Hoffman R, Dye A, Bauer J. Ascorbic acid blocks hyperglycemic impairment of endothelial function in adolescents with type 1 diabetes. Pediatr Diabetes 2012;13:607–10.

206. Ceriello A, Novials A, Ortega E, et al. Vitamin C further improves the protective effect of glucagon-like peptide-1 on acute hypoglycemia-induced oxidative stress, inflammation, and endothelial dysfunction in type 1 diabetes. Diabetes Care 2013;36:4104–8.

207. Sabri M, Tavana E, Ahmadi A, et al. The effect of vitamin C on endothelial function of children with type 1 diabetes: an experimental study. Int J Prev Med 2014;5:999–1004.

208. Cazeau R, Huang H, Bauer J, et al. Effect of Vitamins C and E on Endothelial Function in Type 1 Diabetes Mellitus. J Diabetes Res 2016;2016:3271293.

209. Anderson RA et al. Chromium supplementation of humans with hypoglycemia. Fed Proc 1984;43:471.

210. Stebbing JB et al. Reactive hypoglycemia and magnesium. Magnesium Bull 1982;2:131-4.

211. Shansky A. Vitamin B3 in the alleviation of hypoglycemia. Drug Cosm Ind 1981;129(4):68-69,104-5.

212. Gaby AR, Wright JV. Nutritional regulation of blood glucose. J Advancement Med 1991;4:57-71.

213. Crary EJ, McCarty MF. Potential clinical applications for high-dose nutritional antioxidants. Med Hypotheses 1984;13:77-98.

214. Hudgins AP. Am Practice Digest Treat 1952;3:892-3.

215. Hudgins AP. Vitamins P, C and niacin for dysmenorrhea therapy. West J Surg 1954;Dec:610-1.

216. Santanam N, Kavtaradze N, Murphy A, et al. Antioxidant supplementation reduces endometriosis-related pelvic pain in humans. Transl Res 2013;161:189-95.

217. Cohen JD, Rubin HW. Functional menorrhagia: treatment with bioflavonoids and vitamin C. Curr Ther ResClin Exp 1960;2:539-42.

218. Mukherjee GG, Gajaraj AJ, Mathias J, Marya D. Treatment of abnormal uterine bleeding with micronized flavonoids. Int J Gynaecol Obstet2005;89:156-7.

219. Zuskin E, Valic F, Bouhuys A. Byssinosis and airway responses due to exposure to textile dust. Lung 1976;154:17-24.

220. Bucca C, Rolla G, Oliva A, Farina JC. Effect of vitamin C on histamine bronchial responsiveness of patients with allergic rhinitis. Ann Allergy 1990;65:311-4.

221. Schachter EN, Schlesinger A. The attenuation of exercise-induced bronchospasm by ascorbic acid. Ann Allergy 1982;49:146-51.

222. Tecklenburg SL, Mickleborough TD, Fly AD, et al. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med 2007;Apr 4:Epub ahead of print.

223. Mohsenin V, Dubois AB, Douglas JS. Effect of ascorbic acid on response to methacholine challenge in asthmatic subjects. Am Rev Respir Dis 1983;127:143-7.

224. Zuskin E, Lewis AJ, Bouhuys A. Inhibition of histamine-induced airway constriction by ascorbic acid. J Allergy Clin Immunol 1973;51:218-26.

225. Ting S, Mansfield LE, Yarbrough J. Effects of ascorbic acid on pulmonary functions in mild asthma. J Asthma 1983;20:39-42.

226. Malo JL, Cartier A, Pineau L, et al. Lack of acute effects of ascorbic acid on spirometry and airway responsiveness to histamine in subjects with asthma. J Allergy Clin Immunol 1986;78:1153-8.

227. Kordansky DW, Rosenthal RR, Norman PS. The effect of vitamin C on antigen-induced bronchospasm. J Allergy Clin Immunol 1979;63:61-4.

228. Anah CO, Jarike LN, Baig HA. High dose ascorbic acid in Nigerian asthmatics. Trop Geogr Med 1980;32:132-7.

229. Ruskin SL. Sodium ascorbate in the treatment of allergic disturbances. The role of adrenal cortical hormone-sodium-vitamin C. Am J Dig Dis 1947;14:302-6.

230. Holmes HM, Alexander W. Hay fever and vitamin C. Science 1942;96:497.

231. Ruskin SL. High dose vitamin C in allergy. Am J Dig Dis 1945;12:281.

232. Fortner BR Jr, Danziger RE, Rabinowitz PS, Nelson HS. The effect of ascorbic acid on cutaneous and nasal response to histamine and allergen. J Allergy Clin Immunol 1982;69:484-8.

233. Johnston S, Martin LJ, Cai X. Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr 1992;11:172-6.

234. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci 1993;90:7915-22.

235. Grievink L, Zijlstra AG, Ke X, Brunekreef B. Double-blind intervention trial on modulation of ozone effects on pulmonary function by antioxidant supplements. Am J Epidemiol 1999;149:306-14.

236. Trenga CA, Koenig JQ, Williams PV. Dietary antioxidants and ozone-induced bronchial hyperresponsiveness in adults with asthma. Arch Environ Health 2001;56:242-9.

237. Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Tellez-Rojo MM, Moreno-Macias H, Reyes-Ruiz NI, et al. Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med 2002;166:703-9.

238. Drake IM, Mapstone NP, Schorah CJ, et al. Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication. Gut 1998;42(6):768-71.

239. Waring AJ, Drake IM, Schorah CJ, et al. Ascorbic acid and total vitamin C concentrations in plasma, gastric juice, and gastrointestinal mucosa: effects of gastritis and oral supplementation. Gut 1996;38(2):171-6.

240. Jarosz M, Dzieniszewski J, Dabrowska-Ufniarz E, et al. Effects of high dose vitamin C treatment on Helicobacter pylori infection and total vitamin C concentration in gastric juice. Eur J Cancer Prev 1998;7:449-54.

241. Blumenthal M, Busse WR, Goldberg A, et al, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council and Boston: Integrative Medicine Communications, 1998, 167.

242. Simon JA, Hudes ES. Serum ascorbic acid and gallbladder disease prevalence among US adults. Arch Intern Med 2000;160:931-6.

243. Simon JA. Ascorbic acid and cholesterol gallstones. Med Hypotheses 1993;40:81-4.

244. Simon JA, Grady D, Snabes MC, et al. Ascorbic acid supplement use and the prevalence of gallbladder disease. J Clin Epidemiol 1998;51:257-65.

245. Gustafsson U, Wang F-H, Axelson M, et al. The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time. Eur J Clin Invest 1997;27:387-91.

246. Merkel RL. The use of menadione bisulfite and ascorbic acid in the treatment of nausea and vomiting of pregnancy. Am J Obstet Gynecol 1952;64:416-8.

247. Stein HB, Hasan A, Fox IH. Ascorbic acid-induced uricosuria: a consequence of megavitamin therapy. Ann Intern Med 1976;84:385-8.

248. Huang HY, Appel LJ, Choi MJ, et al. The effects of vitamin C supplementation on serum concentrations of uric acid: results of a randomized controlled trial. Arthritis Rheum 2005;52:1843-7.

249. Greenwood J. Optimum vitamin C intake as a factor in the preservation of disc integrity. Med Ann District of Columbia 1964;33:274-6.

250. Sirsi M. Antimicrobial action of vitamin C on M. tuberculosis and some other pathogenic organisms. Indian J Med Sci 1952;6:252-5.

251. Axelrod DR. Ascorbic acid and urinary pH. JAMA 1985;254:1310-1 [letter].

252. Ochoa-Brust GJ, Fernandez AR, Villanueva-Ruiz GJ, et al. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand 2007;86:783-7.

253. Casanueva E, Ripoll C, Tolentino M, et al. Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial. Am J Clin Nutr 2005;81:859-63.

254. McEvoy CT, Schilling D, Clay N, et al. Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial. JAMA 2014;311:2074–82.

255. Dolske MC, Spollen J, McKay S, et al. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsycholpharmacol Biol Psychiatry 1993;17:765-74.

256. Jariwalla RJ, Harakeh S. Antiviral and immunomodulatory activities of ascorbic acid. Subcell Biochem 1996;25:213-31 [review].

257. Stone I. The Healing Factor: Vitamin C Against Disease. New York: Perigee Books, 1972, 75.

258. Tanzer F, Ozalp I. Leucocyte ascorbic acid concentration and plasma ascorbic acid levels in children with various infections. Mater Med Pol 1993;25:5-8.

259. Joffe MI, Sukha NR, Rabson AR. Lymphocyte subsets in measles. Depressed helper/inducer subpopulation reversed by in vitro treatment with levamisole and ascorbic acid. J Clin Invest 1983;72:971-80.

260. Leibovitz B, Siegel BV. Ascorbic acid, neutrophil function, and the immune response. Int J Vitam Nutr Res 1978;48:159-64.

261. Vojdani A, Ghoneum M. In vivo effect of ascorbic acid on enhancement of human natural killer cell activity. Nutr Res 1993;13:753-64.

262. Young RW. Solar radiation and age-related macular degeneration. Surv Ophthalmol 1988:32:252-69.

263. Christen WG, Glynn RJ, Sesso HD, et al. Vitamins E and C and medical record-confirmed age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 2012;119:1642-9.

264. Masaki KH, Losonczy KG, Izmirlian G, et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000;54:1265-72.

265. CJ Smith. Non-hormonal control of vaso-motor flushing in menopausal patients. Chicago Med 1964;67:193-5.

266. Leibovitz B, Siegel BV. Ascorbic acid, neutrophil function, and the immune response. Int J Vitam Nutr Res 1978;48:159-64.

267. Vojdani A, Ghoneum M. In vivo effect of ascorbic acid on enhancement of human natural killer cell activity. Nutr Res 1993;13:753-64.

268. Sandyk R, Kanofsky JD. Vitamin C in the treatment of schizophrenia. Int J Neurosci 1993;68:67-71.

269. Kanofsky JD, Sandyk R. Antioxidants in the treatment of schizophrenia. Int J Neurosci 1992;62:97-100 [letter].

270. Beauclair L, Vinogradov S, Riney SJ, et al. An adjunctive role for ascorbic acid in the treatment of schizophrenia? J Clin Psychopharmacol 1987;7:282-3 [letter].

271. Pitt B, Pollitt N. Ascorbic acid and chronic schizophrenia. Br J Psychiatry 1971;118:227-8.

272. Grant FW, Cowen MA, Ozerengin MF, Bigelow N. Nutritional requirements in mental illness. I. Ascorbic acid retention in schizophrenia. A reexamination. Biol Psychiatry 1973;5:289-94.

273. Pitt B. Vitamin C and schizophrenia. Lancet 1974;2:1153-4 [letter].

274. Suboticanec K, Folnegovic-Smalc V, Turcin R, et al. Plasma levels and urinary vitamin C excretion in schizophrenic patients. Hum Nutr Clin Nutr 1986;40:421-8.

275. Suboticanec K, Folnegovic-Smalc V, Korbar M, et al. Vitamin C status in chronic schizophrenia. Biol Psychiatry 1990;28:959-66.

276. Masaki KH, Losonczy KG, Izmirlian G, et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000;54:1265-72.

277. Naylor GJ. Vanadium and manic depressive psychosis. Nutr Health 1984;3:79-85 [review].

278. Naylor GJ, Smith AH. Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med 1981;11:249-56.

279. Kay DS, Naylor GJ, Smith AH, Greenwood C. The therapeutic effect of ascorbic acid and EDTA in manic-depressive psychosis: double-blind comparisons with standard treatments. Psychol Med 1984;14:533-9.

280. Kanter M. Free radicals, exercise and antioxidant supplementation. Proc Nutr Soc 1998;57:9-13 [review].

281. Dekkers JC, Van Doornen LJ, Kemper HC. The role of antioxidant vitamins and enzymes in the prevention of exercise-induced muscle damage. Sports Med 1996;21(3):213-38 [review].

282. Jakeman P, Maxwell S. Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise. Eur J Appl Physiol 1993;67:426-30.

283. Kaminski M, Boal R. An effect of ascorbic acid on delayed-onset muscle soreness. Pain 1992;50:317-21.

284. Thompson D, Williams C, McGregor SJ, et al. Prolonged vitamin C supplementation and recovery from demanding exercise. Int J Sport Nutr Exerc Metab 2001;11:466-81.

285. Thompson D, Williams C, Garcia-Roves P, et al. Post-exercise vitamin C supplementation and recovery from demanding exercise. Eur J Appl Physiol 2003;89:393-400.

286. Itoh H, Ohkuwa T, Yamazaki Y, et al. Vitamin E supplementation attenuates leakage of enzymes following 6 successive days of running training. Int J Sports Med 2000;21:369-74.

287. McBride JM, Kraemer WJ, Triplett-McBride T, Sebastianelli W. Effect of resistance exercise on free radical production. Med Sci Sports Exerc 1998;30:67-72.

288. Evans WJ. Vitamin E, vitamin C, and exercise. Am J Clin Nutr 2000;72:647S-52S [review].

289. Dawson B, Henry GJ, Goodman C, et al. Effect of Vitamin C and E supplementation on biochemical and ultrastructural indices of muscle damage after a 21 km run. Int J Sports Med 2002;23:10-5.

290. Beaton LJ, Allan DA, Tarnopolsky MA, et al. Contraction-induced muscle damage is unaffected by vitamin E supplementation. Med Sci Sports Exerc 2002;34:798-805.

291. Petersen EW, Ostrowski K, Ibfelt T, et al. Effect of vitamin supplementation on cytokine response and on muscle damage after strenuous exercise. Am J Physiol Cell Physiol 2001;280:C1570-5.

292. Kanter MM, Nolte LA, Holloszy JO. Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise. J Appl Physiol 1993;74:965-9.

293. Kaikkonen J, Kosonen L, Nyyssonen K, et al. Effect of combined coenzyme Q10 and d-alpha-tocopheryl acetate supplementation on exercise-induced lipid peroxidation and muscular damage: a placebo-controlled double-blind study in marathon runners. Free Radic Res 1998;29:85-92.

294. Singh A, Failla ML, Deuster PA. Exercise-induced changes in immune function: effects of zinc supplementation. J Appl Physiol 1994;76:2298-303.

295. Johnston CS, Swan PD, Corte C. Substrate utilization and work efficiency during submaximal exercise in vitamin C depleted-repleted adults. Int J Vitam Nutr Res 1999;69:41-4.

296. Gerster H. The role of vitamin C in athletic performance. J Am Coll Nutr 1989;8:636-43 [review].

297. Tiidus PM, Houston ME. Vitamin E status and response to exercise training. Sports Med 1995;20:12-23 [review].

298. Akova B, Surmen-Gur E, Gur H, et al. Exercise-induced oxidative stress and muscle performance in healthy women: role of vitamin E supplementation and endogenous oestradiol. Eur J Appl Physiol 2001;84:141-7.

299. Simon-Schnass I, Pabst H. Influence of vitamin E on physical performance. Int J Vitam Nutr Res 1988;58:49-54.

300. Shepard RJ. Vitamin E and athletic performance. J Sports Med 1983;23:461-70 [review].

301. Kanter M. Free radicals, exercise and antioxidant supplementation. Proc Nutr Soc 1998;57:9-13 [review].

302. Dekkers JC, Van Doornen LJ, Kemper HC. The role of antioxidant vitamins and enzymes in the prevention of exercise-induced muscle damage. Sports Med 1996;21(3):213-38 [review].

303. Jakeman P, Maxwell S. Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise. Eur J Appl Physiol 1993;67:426-30.

304. Kaminski M, Boal R. An effect of ascorbic acid on delayed-onset muscle soreness. Pain 1992;50:317-21.

305. Thompson D, Williams C, McGregor SJ, et al. Prolonged vitamin C supplementation and recovery from demanding exercise. Int J Sport Nutr Exerc Metab 2001;11:466-81.

306. Thompson D, Williams C, Garcia-Roves P, et al. Post-exercise vitamin C supplementation and recovery from demanding exercise. Eur J Appl Physiol 2003;89:393-400.

307. Itoh H, Ohkuwa T, Yamazaki Y, et al. Vitamin E supplementation attenuates leakage of enzymes following 6 successive days of running training. Int J Sports Med 2000;21:369-74.

308. McBride JM, Kraemer WJ, Triplett-McBride T, Sebastianelli W. Effect of resistance exercise on free radical production. Med Sci Sports Exerc 1998;30:67-72.

309. Evans WJ. Vitamin E, vitamin C, and exercise. Am J Clin Nutr 2000;72:647S-52S [review].

310. Dawson B, Henry GJ, Goodman C, et al. Effect of Vitamin C and E supplementation on biochemical and ultrastructural indices of muscle damage after a 21 km run. Int J Sports Med 2002;23:10-5.

311. Beaton LJ, Allan DA, Tarnopolsky MA, et al. Contraction-induced muscle damage is unaffected by vitamin E supplementation. Med Sci Sports Exerc 2002;34:798-805.

312. Petersen EW, Ostrowski K, Ibfelt T, et al. Effect of vitamin supplementation on cytokine response and on muscle damage after strenuous exercise. Am J Physiol Cell Physiol 2001;280:C1570-5.

313. Kanter MM, Nolte LA, Holloszy JO. Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise. J Appl Physiol 1993;74:965-9.

314. Kaikkonen J, Kosonen L, Nyyssonen K, et al. Effect of combined coenzyme Q10 and d-alpha-tocopheryl acetate supplementation on exercise-induced lipid peroxidation and muscular damage: a placebo-controlled double-blind study in marathon runners. Free Radic Res 1998;29:85-92.

315. Singh A, Failla ML, Deuster PA. Exercise-induced changes in immune function: effects of zinc supplementation. J Appl Physiol 1994;76:2298-303.

316. Johnston CS, Swan PD, Corte C. Substrate utilization and work efficiency during submaximal exercise in vitamin C depleted-repleted adults. Int J Vitam Nutr Res 1999;69:41-4.

317. Gerster H. The role of vitamin C in athletic performance. J Am Coll Nutr 1989;8:636-43 [review].

318. Paschalis V, Theodorou AA, Kyparos A, et al. Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation. Eur J Nutr 2016;55:45–53.

319. Tiidus PM, Houston ME. Vitamin E status and response to exercise training. Sports Med 1995;20:12-23 [review].

320. Akova B, Surmen-Gur E, Gur H, et al. Exercise-induced oxidative stress and muscle performance in healthy women: role of vitamin E supplementation and endogenous oestradiol. Eur J Appl Physiol 2001;84:141-7.

321. Simon-Schnass I, Pabst H. Influence of vitamin E on physical performance. Int J Vitam Nutr Res 1988;58:49-54.

322. Shepard RJ. Vitamin E and athletic performance. J Sports Med 1983;23:461-70 [review].

323. Kanter M. Free radicals, exercise and antioxidant supplementation. Proc Nutr Soc 1998;57:9-13 [review].

324. Dekkers JC, Van Doornen LJ, Kemper HC. The role of antioxidant vitamins and enzymes in the prevention of exercise-induced muscle damage. Sports Med 1996;21(3):213-38 [review].

325. Jakeman P, Maxwell S. Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise. Eur J Appl Physiol 1993;67:426-30.

326. Kaminski M, Boal R. An effect of ascorbic acid on delayed-onset muscle soreness. Pain 1992;50:317-21.

327. Thompson D, Williams C, McGregor SJ, et al. Prolonged vitamin C supplementation and recovery from demanding exercise. Int J Sport Nutr Exerc Metab 2001;11:466-81.

328. Thompson D, Williams C, Garcia-Roves P, et al. Post-exercise vitamin C supplementation and recovery from demanding exercise. Eur J Appl Physiol 2003;89:393-400.

329. Itoh H, Ohkuwa T, Yamazaki Y, et al. Vitamin E supplementation attenuates leakage of enzymes following 6 successive days of running training. Int J Sports Med 2000;21:369-74.

330. McBride JM, Kraemer WJ, Triplett-McBride T, Sebastianelli W. Effect of resistance exercise on free radical production. Med Sci Sports Exerc 1998;30:67-72.

331. Evans WJ. Vitamin E, vitamin C, and exercise. Am J Clin Nutr 2000;72:647S-52S [review].

332. Dawson B, Henry GJ, Goodman C, et al. Effect of Vitamin C and E supplementation on biochemical and ultrastructural indices of muscle damage after a 21 km run. Int J Sports Med 2002;23:10-5.

333. Beaton LJ, Allan DA, Tarnopolsky MA, et al. Contraction-induced muscle damage is unaffected by vitamin E supplementation. Med Sci Sports Exerc 2002;34:798-805.

334. Petersen EW, Ostrowski K, Ibfelt T, et al. Effect of vitamin supplementation on cytokine response and on muscle damage after strenuous exercise. Am J Physiol Cell Physiol 2001;280:C1570-5.

335. Kanter MM, Nolte LA, Holloszy JO. Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise. J Appl Physiol 1993;74:965-9.

336. Kaikkonen J, Kosonen L, Nyyssonen K, et al. Effect of combined coenzyme Q10 and d-alpha-tocopheryl acetate supplementation on exercise-induced lipid peroxidation and muscular damage: a placebo-controlled double-blind study in marathon runners. Free Radic Res 1998;29:85-92.

337. Singh A, Failla ML, Deuster PA. Exercise-induced changes in immune function: effects of zinc supplementation. J Appl Physiol 1994;76:2298-303.

338. Johnston CS, Swan PD, Corte C. Substrate utilization and work efficiency during submaximal exercise in vitamin C depleted-repleted adults. Int J Vitam Nutr Res 1999;69:41-4.

339. Gerster H. The role of vitamin C in athletic performance. J Am Coll Nutr 1989;8:636-43 [review].

340. Tiidus PM, Houston ME. Vitamin E status and response to exercise training. Sports Med 1995;20:12-23 [review].

341. Akova B, Surmen-Gur E, Gur H, et al. Exercise-induced oxidative stress and muscle performance in healthy women: role of vitamin E supplementation and endogenous oestradiol. Eur J Appl Physiol 2001;84:141-7.

342. Simon-Schnass I, Pabst H. Influence of vitamin E on physical performance. Int J Vitam Nutr Res 1988;58:49-54.

343. Shepard RJ. Vitamin E and athletic performance. J Sports Med 1983;23:461-70 [review].

344. Fraga CG, Motchnik PA, Shigenaga MK, et al. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci 1991;88:11003-6.

345. Dawson EB, Harris WA, Teter MC, Powell LC. Effect of ascorbic acid supplementation on the sperm quality of smokers. Fertil Steril 1992;58:1034-9.

346. Dawson EB, Harris WA, McGanity WJ. Effect of ascorbic acid on sperm fertility. Fed Proc 1983;42:531 [abstr 31403].

347. Dawson EB, Harris WA, Powell LC. Relationship between ascorbic acid and male fertility. In: Aspects of Some Vitamins, Minerals and Enzymes in Health and Disease, ed. GH Bourne. World Rev Nutr Diet 1990;62:1-26 [review].

348. Dawson EB, Harris WA, Rankin WE, et al. Effect of ascorbic acid on male fertility. Ann N Y Acad Sci 1987;498:312-23.

349. Rolf C, Cooper TG, Yeung CH, Nieschlag E. Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Hum Reprod 1999;14:1028-33.

350. Gaby, AR. Nutritional Medicine. Concord, NH: Fritz Perlberg Publishing, 2011.

351. Balz F. Antioxidant Vitamins and Heart Disease. Presented at the 60th Annual Biology Colloquium, Oregon State University, February 25, 1999.

352. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23.

353. 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 1996;93:3704-9.

354. 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.

355. Hemilä H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hypotheses 1999;52:171-8.

356. Kharb S. Total free radical trapping antioxidant potential in pre-eclampsia. Int J Gynaecol Obstet 2000;69:23-6.

357. Simon JA, Hudes ES. Serum ascorbic acid and gallbladder disease prevalence among US adults. Arch Intern Med 2000;160:931-6.

358. Makoff R. Vitamin replacement therapy in renal failure patients. Miner Electrolyte Metab 1999;25:349-51 [review].

359. Johnston CS. Biomarkers for establishing a tolerable upper intake level for vitamin C. Nutr Rev 1999;57:71-7.

360. Wilson JD. Vitamin deficiency and excess. In Fauci AS, Braunwald E, Isselbacher KJ, et al. (eds). Harrison's Principles of Internal Medicine, 14th ed. New York, McGraw Hill, 1998, 487.

361. Cochrane WA. Overnutrition in prenatal and neonatal life: a problem? Can Med Assoc J 1965;93:893-9.

362. Gaby AR. The myth of rebound scurvy. Townsend Letter for Doctors 2000;June:122.

363. Dwyer J, Nicholson LM, Shircore A, et al. Vitamin C intake and progression of carotid atherosclerosis. The Los Angeles Atherosclerosis Study. American Heart Association Annual Meeting. March 2, 2000 [abstract].

364. Piesse JW. Nutritional factors in calcium containing kidney stones with particular emphasis on vitamin C. Int Clin Nutr Rev 1985;5:110-29 [review].

365. Ringsdorf WM, Cheraskin WM. Medical complications from ascorbic acid: a review and interpretation (part one). J Holistic Med 1984;6:49-63.

366. Hoffer A. Ascorbic acid and kidney stones. Can Med Assoc J 1985;32:320 [letter].

367. Wandzilak TR, D'Andre SD, Davis PA, Williams HE. Effect of high dose vitamin C on urinary oxalate levels. J Urol 1994;151:834-7.

368. Levine M. Vitamin C and optimal health. Presented at the February 25, 1999 60th Annual Biology Colloquium, Oregon State University, Corvallis, Oregon.

369. 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 1996;93:3704-9.

370. Auer BL, Auer D, Rodgers AL. Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of vitamin C. Eur J Clin Invest 1998;28:695-700.

371. Branch DR. High-dose vitamin C supplementation increases plasma glucose. Diabetes Care1999;22:1218 [letter].

Copyright © 2020 TraceGains, Inc. All rights reserved.

Learn more about TraceGains, the company.

The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2020.

Copyright © 2020 TraceGains, Inc. All rights reserved.

The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. Self-treatment is not recommended for life-threatening conditions that require medical treatment under a doctor's care. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2020.