Deficiencies of iron, vitamin B12, and folic acid are the most common nutritional causes of anemia.¹ Although rare, severe deficiencies of several other vitamins and minerals, including vitamin A,^{2 , 3} vitamin B2,⁴ vitamin B6,^{5 , 6} vitamin C,⁷ and copper,^{8 , 9} can also cause anemia by various mechanisms. Rare genetic disorders can cause anemias that may improve with large amounts of supplements such as vitamin B1.^{10 , 11}

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.^{12 , 13}

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.^{14 , 15 , 16} However, taking vitamin C only after such exercise was not effective in another double-blind study.¹⁷ 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,^{18 , 19 , 20} several studies have not found such benefits,^{21 , 22 , 23 , 24} 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,²⁵ 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.²⁶

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.^{27 , 28} Similarly, vitamin E has not benefited exercise performance, ^{29 , 30} except possibly at high altitudes. ^{31 , 32}

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.³³ 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.³⁴

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,³⁵ although it is not known how much vitamin E is needed to produce that protective effect.

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.³⁶ Flavonoids are often recommended along with vitamin C. Flavonoids are vitamin-like substances that can help strengthen capillaries and therefore may also help with bruising.³⁷ 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.³⁸ 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.³⁹ Controlled research is needed to better establish whether vitamin C and flavonoids are effective for easy bruising.

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,^{40 , 41} 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.⁴² 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.^{43 , 44} 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.⁴⁵

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%.”⁴⁶ 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.⁴⁷ 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.

People who are deficient in vitamin C may be at increased risk for periodontal disease.⁴⁸ 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.⁴⁹ 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.

Several studies have shown that supplementing with vitamin C can significantly reduce elevated intraocular pressure in individuals with glaucoma.⁵⁰ 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.”⁵¹ 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.

Vitamin C has been reported to protect blood vessels from problems associated with heart attack risk in a variety of ways.^{52, 53, 54} However, research attempting to link vitamin C directly to protection from heart attacks has been inconsistent.^{55, 56} 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.^{57, 58} However, in trials comparing acceptable (i.e., non-deficient) vitamin C levels to even higher levels, additional vitamin C has not been protective.⁵⁹ 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.

Vitamin C has antiviral activity, and may help prevent viral infections⁶⁴ or, in the case of the common cold, reduce the severity and duration of an infection.⁶⁵ Most studies on the common cold used 1 to 4 grams of vitamin C per day.

Vitamin C protects sperm from oxidative damage.⁶⁶ Supplementing vitamin C improves the quality of sperm in smokers.⁶⁷ When sperm stick together (a condition called agglutination), fertility is reduced. Vitamin C reduces sperm agglutination,⁶⁸ and supplementation with 200–1,000 mg per day increased the fertility of men with this condition in a controlled study.^{69, 70} 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.⁷¹

Animal studies suggest that supplementing with vitamin C can reduce blood levels of stress-related hormones and other measures of stress.^{72 , 73 , 74 , 75} 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.^{76 , 77} 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.⁷⁸ 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.⁷⁹ 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.

Antioxidants may protect the skin from sunburn due to free radical–producing ultraviolet rays.⁸⁰ 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.^{81, 82, 83}

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.^{84 , 85 , 86 , 87 , 88}

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.⁸⁹ 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.⁹⁰ 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.⁹¹

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.⁹² 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.⁹³ Similarly, in a controlled trial, a combination of selenium, copper, and vitamins was found to be ineffective.⁹⁴

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.^{95 , 96}

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,⁹⁷ and vitamin C deficiency causes delayed healing.⁹⁸ 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.^{99, 100} 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.^{101, 102}

Supplementation with 1 gram of vitamin C per day reduces the tendency of the bronchial passages to go into spasm,¹⁰³ an action that has been confirmed in double-blind research.¹⁰⁴ 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.^{105 , 106} Two other preliminary trials found that vitamin C supplementation reduced bronchial reactivity to metacholine, a drug that causes bronchial constriction.^{107 , 108} However, other studies,¹⁰⁹ including two double-blind trials,^{110 , 111} 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.¹¹² 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).¹¹³

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.¹¹⁴ Vitamin C also protects LDL.¹¹⁵

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.¹¹⁶ In a double-blind trial,¹¹⁷ 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.

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.^{118 , 119}

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.^{120 , 121 , 122} However, taking vitamin C only after such exercise was not effective in another double-blind study.¹²³ 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,^{124 , 125 , 126} several studies have not found such benefits,^{127 , 128 , 129 , 130} 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,¹³¹ 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.¹³²

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.^{133 , 134} Similarly, vitamin E has not benefited exercise performance, ^{135 , 136} except possibly at high altitudes. ^{137 , 138}

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.¹³⁹ 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.

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.^{140 , 141}

The major antioxidants in the lens of the eye are vitamin C¹⁴² and glutathione (a molecule composed of three amino acids).¹⁴³ Vitamin C is needed to activate vitamin E,¹⁴⁴ 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.¹⁴⁵

Vitamin C levels in the eye decrease with age.¹⁴⁶ However, supplementing with vitamin C prevents this decrease¹⁴⁷ and has been linked to a lower risk of developing cataracts.^{148 , 149} Healthy people are more likely to take vitamin C and vitamin E supplements than those with cataracts according to some,¹⁵⁰ but not all,¹⁵¹ studies. Dietary vitamin C intake has not been consistently associated with protection from cataracts.^{152 , 153} Nonetheless, because people who supplement with vitamin C have developed far fewer cataracts in some research,^{154 , 155} 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.¹⁵⁶

Vitamin C has been shown to inactivate herpes viruses in the test tube.¹⁵⁷ 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%.¹⁵⁸

In a 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 two months resulted in an improvement of pain in 43% of women, whereas none of the women receiving a placebo reported pain relief.¹⁵⁹

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.¹⁶⁰

When H. pylori causes gastritis, free radical levels rise in the stomach lining.¹⁶¹ 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.¹⁶² In another trial, vitamin C supplementation (5 grams per day divided into several doses for four weeks) appeared to eliminate H. pylori infection.¹⁶³ 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.

People who are deficient in vitamin C may be at increased risk for periodontal disease.¹⁶⁴ 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.¹⁶⁵ 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,¹⁶⁶ including double-blind evidence,¹⁶⁷ 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;¹⁶⁸ 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.¹⁶⁹

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.¹⁷⁰ 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.¹⁷¹ 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.

Most,^{172 , 173} but not all,¹⁷⁴ 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.¹⁷⁵ Burn victims have also experienced fewer infections after receiving trace mineral supplements in double-blind research.¹⁷⁶ 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 levels¹⁷⁷ and enhancing the activity of certain immune cells.^{178, 179} Two studies came to opposite conclusions about the ability of vitamin C to improve immune function in the elderly,^{180, 181} and two other studies did not agree on whether vitamin C could protect people from hepatitis.^{182, 183} 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.¹⁸⁴ 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.¹⁸⁵ 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.¹⁸⁶ 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.¹⁸⁷ To what extent immune-boosting combinations of antioxidants actually reduce the risk of infection remains unknown.

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.¹⁸⁸ 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.^{189 , 190} Such high amounts, however, should only be used under the supervision of a healthcare professional.

Some preliminary studies have indicated that high dietary intakes of antioxidant nutrients, especially vitamin E, are associated with a low risk of Parkinson’s disease,^{191 , 192} even though Parkinson’s patients are not deficient in vitamin E.^{193 , 194} The correlation between protection from Parkinson’s and dietary vitamin E may be not be due to the vitamin E itself, however. Legumes (beans and peas) contain relatively high amounts of vitamin E. Independent of their vitamin E content, consumption of legumes has been associated with low risk of Parkinson’s disease.¹⁹⁵ In other words, high vitamin E intake may be a marker for diets high in legumes, and legumes may protect against Parkinson’s disease for reasons unrelated to their vitamin E content.

Interest in the relationship between antioxidants and Parkinson’s disease led to a preliminary trial using high amounts of vitamin C and vitamin E in early Parkinson’s disease¹⁹⁶ and to a large ten-year controlled trial of high amounts of vitamin E combined with the drug deprenyl.¹⁹⁷ In the trial combining vitamins C and E, people with early Parkinson’s disease given 750 mg of vitamin C and 800 IU of vitamin E four times each day (totaling 3,000 mg of vitamin C and 3,200 IU of vitamin E per day) were able to delay the need for drug therapy (i.e., L-dopa or selegiline) by an average of about two and a half years, compared with those not taking the vitamins.¹⁹⁸ The ten-year controlled trial used 2,000 IU of vitamin E per day found no benefit in slowing or improving the disease.¹⁹⁹ The difference in the outcomes between these two trials might be due to the inclusion of vitamin C and/or the higher amount of vitamin E used in the successful trial. However, the difference might also be due to a better study design in the trial that found vitamin E to be ineffective.

The amounts of vitamin E used in the above trials were very high, because raising antioxidant levels in brain tissue is quite difficult to achieve.²⁰⁰ In fact, some researchers have found that even extremely high intakes of vitamin E (4,000 IU per day) failed to increase brain vitamin E levels.²⁰¹ The difficulty in increasing brain vitamin E levels may explain the poor results of the large, controlled trial.

Vitamin C deficiency can be detrimental to immune function in hospitalized patients,²⁰² and one study found that half of surgery patients recovering at home had low dietary intakes of vitamin C.²⁰³ Vitamin C is also a critical nutrient for wound healing,^{204, 205} but studies of vitamin C supplementation have shown only minor effects on the healing of surgical wounds.^{206, 207} Vitamin C deficiency also can increase the risk of excessive bleeding in the surgical setting.²⁰⁸

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%.²⁰⁹ 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.

Up to 6 grams daily of vitamin C has been reported to be beneficial for people with schizophrenia;^{210 , 211} in one case the addition of 400 IU daily of vitamin E enhanced this benefit.²¹² 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.²¹³ 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.^{214 , 215 , 216} 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.^{217 , 218}

Antioxidants such as vitamin C, vitamin E, and glutathione are depleted in healing skin tissue.²¹⁹ One animal study found that vitamin E (alpha-tocopherol) applied to the skin shortened the healing time of skin ulcers.²²⁰ 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.²²¹ A controlled human trial found that 400 IU of vitamin E daily improved the results of skin graft surgery for chronic venous ulcers.²²² 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,²²³ and in a preliminary study,²²⁴ 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.²²⁵ 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,²²⁶ 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.²²⁷

Antioxidant supplements, including vitamin C and vitamin E, may help prevent exercise-related muscle injuries by neutralizing free radicals produced during strenuous activities.²²⁸ 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.^{229, 230} 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,^{231, 232, 233} but no measurable benefits in exercise recovery have been reported.²³⁴ 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.²³⁵

Vitamin C is needed to make collagen, the “glue” that strengthens connective tissue. Injury, at least when severe, appears to increase vitamin C requirements,²³⁶ and vitamin C deficiency causes delayed healing from injury.²³⁷ Preliminary human studies have suggested that vitamin C supplementation in non-deficient people can speed healing of various types of trauma, including musculoskeletal injuries,^{238, 239} but double-blind research has not confirmed these effects for athletic injuries, which included sprains and strains.²⁴⁰

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.^{241, 242} The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.^{243, 244} 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.²⁴⁵ Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.^{246, 247}

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.^{248, 249} The topical use of the hormone melatonin has been shown to protect human skin against ultraviolet rays in double-blind research.^{250, 251} 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.²⁵² Other studies in which topical antioxidants were applied after ultraviolet exposure have found no benefits.^{253, 254}

People with type 1 diabetes appear to have low vitamin C levels.²⁵⁵ As with vitamin E, vitamin C may reduce glycosylation.²⁵⁶ Vitamin C also lowers sorbitol levels in people with diabetes.²⁵⁷ Sorbitol is a sugar that can accumulate inside the cells and damage the eyes, nerves, and kidneys of people with diabetes. Vitamin C supplementation (500 mg twice a day for one year) has significantly reduced urinary protein loss in people with diabetes. Urinary protein loss (also called proteinuria) is associated with poor prognosis in diabetes.²⁵⁸ Many doctors suggest that people with diabetes supplement with 1 to 3 grams per day of vitamin C. Higher amounts could be problematic, however. In one person, 4.5 grams per day was reported to increase blood sugar levels.²⁵⁹

One study examined antioxidant supplement intake, including both vitamins E and C, and the incidence of diabetic eye damage (retinopathy).²⁶⁰ A surprising finding was that people with extensive retinopathy had a greater likelihood of having taken vitamin C and vitamin E supplements. The outcome of this study, however, does not fit with most other published data and might simply reflect the fact that sicker people are more likely to take supplements in hopes of getting better. For the present, most doctors remain relatively unconcerned about the outcome of this isolated report.

As with vitamin E, vitamin C may reduce glycosylation.²⁶¹ Vitamin C also lowers sorbitol levels in people with diabetes.²⁶² Sorbitol is a sugar that can accumulate inside the cells and damage the eyes, nerves, and kidneys of people with diabetes. Vitamin C may improve glucose tolerance in type 2 diabetes,^{263 , 264} although not every study confirms this benefit.²⁶⁵ Vitamin C supplementation (500 mg twice a day for one year) has significantly reduced urinary protein loss in people with diabetes. Urinary protein loss (also called proteinuria) is associated with poor prognosis in diabetes.²⁶⁶ Many doctors suggest that people with diabetes supplement with 1 to 3 grams per day of vitamin C. Higher amounts could be problematic, however. In one person, 4.5 grams per day was reported to increase blood sugar levels.²⁶⁷

One study examined antioxidant supplement intake, including both vitamins E and C, and the incidence of diabetic retinopathy (damage to the eyes caused by diabetes).²⁶⁸ Surprisingly, people with extensive retinopathy had a greater likelihood of having taken vitamin C and vitamin E supplements. The outcome of this trial, however, does not fit with most other published data and might simply reflect the fact that sicker people are more likely to take supplements in hopes of getting better. For the present, most doctors remain relatively unconcerned about the outcome of this isolated report.

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.²⁶⁹ 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,²⁷⁰ 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.²⁷¹

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).²⁷² Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.

The daily combination of 3 grams of vitamin C, 3 grams of niacin, 600 mg of vitamin B6, and 600 IU of vitamin E has been used by researchers from the University of Mississippi Medical Center in an attempt to reduce anxiety and depression in alcoholics.²⁷³ Although the effect of vitamin supplementation was no better than placebo in treating alcohol-associated depression, the vitamins did result in a significant drop in anxiety within three weeks of use. Because of possible side effects, anyone taking such high amounts of niacin and vitamin B6 must do so only under the care of a doctor.

Although the incidence of B-complex deficiencies is known to be high in alcoholics, the incidence of other vitamin deficiencies remains less clear.²⁷⁴ Nonetheless, deficiencies of vitamin A, vitamin D, vitamin E, and vitamin C are seen in many alcoholics. While some reports have suggested it may be safer for alcoholics to supplement with beta-carotene instead of vitamin A,²⁷⁵ potential problems accompany the use of either vitamin A or beta-carotene in correcting the deficiency induced by alcoholism.²⁷⁶ These problems result in part because the combinations of alcohol and vitamin A or alcohol and beta-carotene appear to increase potential damage to the liver. Thus, vitamin A-depleted alcoholics require a doctor’s intervention, including supplementation with vitamin A and beta-carotene accompanied by assessment of liver function. Supplementing with vitamin C, on the other hand, appears to help the body rid itself of alcohol.²⁷⁷ Some doctors recommend 1 to 3 grams per day of vitamin C.

Vitamin C alone, at 400 mg daily, had no effect on amenorrhea in one preliminary trial, although it was associated with the return of ovulation in some women who were menstruating regularly but not ovulating. In a second phase of the trial, the same amount of vitamin C was combined with a drug that affects female hormone levels, and this combination was associated with return of ovulation in almost half of amenorrheic women who had not benefited from the drug alone.²⁷⁸ More studies of the effect of vitamin C on amenorrhea are needed.

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.²⁷⁹ 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.²⁸⁰ 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.²⁸¹ 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.²⁸² 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.

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.²⁸³ 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.²⁸⁴ 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.²⁸⁵ Until more is known, people with bipolar illness should avoid supplements containing vanadium and consider supplementing with vitamin C.

Vitamin C has been demonstrated in test tube, animal, and human studies to have immune-enhancing and direct antiviral properties.²⁸⁶ Preliminary observations made on the effect of vitamin C on viral infections have involved both measles and chicken pox.²⁸⁷ An active immune system uses vitamin C rapidly, and blood levels fall in children with bacterial or viral infections.²⁸⁸ 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.²⁸⁹ 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.

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.²⁹⁰ As yet, the effects of supplementing with vitamin C in people with COPD have not been studied.

Women, but not men, who took vitamin C supplements were reported to have a reduced risk of colon cancer, according to a preliminary report.²⁹¹

Familial polyposis is a disease that usually leads to colon cancer. In a double-blind study, supplementation with 3 grams per day of vitamin C for nine months led to a reduction in the number of precancerous polyps in people with familial polyposis.²⁹² In another controlled trial, combining vitamin C with vitamin A and vitamin E led to a dramatic reduction in the recurrence of adenomatous polyps—another precancerous condition of the colon.²⁹³ However, other trials attempting to prevent recurrence of adenomatous polyps using vitamin C alone or in combination with other vitamins have reported no therapeutic effect²⁹⁴ or only weak trends favoring the group given supplements.^{295 , 296}

Therefore, the ability of vitamin C supplementation to reduce recurrences of precancerous polyps remains unproven. Whether long-term supplementation with vitamin C would directly help in the prevention of colon cancer has not yet been studied.

Cancer patients’ white blood cells (WBCs) have been reported to contain low levels of vitamin C when compared with WBCs of healthy people.²⁹⁷ In the 1970s, Linus Pauling and Ewan Cameron, a Scottish surgeon, gave 100 terminal cancer patients 10 grams of vitamin C per day (2.5 grams four times per day) and followed them until death.²⁹⁸ These patients lived an average of 210 days, compared with an average of 50 days for similar cancer patients who did not receive vitamin C. A follow-up report on the same patients revealed an even greater gap in survival time between the two groups.²⁹⁹

Mayo Clinic researchers studied the effect of vitamin C in terminal cancer patients, but unlike Pauling and Cameron, they gave about half of the patients a placebo. The Mayo Clinic findings showed that vitamin C had no therapeutic effect.³⁰⁰ Pauling claimed that his trial differed from the Mayo Clinic study because his patients had received much less chemotherapy. In theory, chemotherapy might inactivate vitamin C’s anticancer effects.

The Mayo Clinic therefore conducted a second controlled study, this time in colon cancer patients who had not received chemotherapy.³⁰¹ Again, the Mayo Clinic reported that vitamin C was ineffective. In response, Pauling said that his patients had been given vitamin C supplements until they died. The Mayo Clinic’s colon cancer patients, in contrast, were no longer given vitamin C once their cancers progressed. Thus Pauling’s premise—that vitamin C would increase survival in terminal cancer patients if they continued to take vitamin C until they died—had not been adequately tested by the Mayo Clinic.

Pauling was also concerned that some of the colon cancer patients assigned to the placebo group may have been taking vitamin C supplements even though they had been instructed not to. The Mayo Clinic had made only limited attempts to monitor whether people in the control group were surreptitiously taking vitamin C.

In an attempt to duplicate Pauling’s findings, Japanese researchers conducted a trial with terminal cancer patients.³⁰² As with the Pauling trial, a control group existed but was not given placebo. Patients assigned to vitamin C lived an average of 246 days compared with 43 days in those not receiving vitamin C. Thus, the Japanese research results independently confirmed the outcome of the Pauling and Cameron trial. Nonetheless, the negative reports from the controlled Mayo Clinic trials—despite criticisms of those trials—leave the issue unresolved. None of these studies investigated what effect, if any, vitamin C might have in patients with early stage colon cancer.

Vitamin C supplementation has been reported to stimulate immune function.^{303, 304} 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.

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.³⁰⁵ 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.

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.³⁰⁶ Although this does not prove that vitamin C supplements can prevent or treat gallstones, some researchers believe this is plausible.³⁰⁷ 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.³⁰⁸ 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.³⁰⁹ While many doctors recommend vitamin C supplementation to people with a history of gallstones, supportive evidence remains preliminary.

Nutritional supplements recommended by some doctors for prevention and treatment of periodontitis include vitamin C (people with periodontitis are often found to be deficient),³¹⁰ vitamin E, selenium, zinc, coenzyme Q10, and folic acid.³¹¹ Folic acid has also been shown to reduce the severity of gingivitis when taken as a mouthwash.³¹²

Although vitamin C has antihistamine activity, and supplementation, in preliminary research,^{313 , 314} 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.³¹⁵ Thus, while some doctors recommend that hay fever sufferers take 1,000–3,000 mg of vitamin C per day, supportive evidence remains weak.

Vitamin C in the amount of 2 grams per day was reported in a preliminary trial to prevent hepatitis infection in individuals receiving blood transfusions.³²⁴ This report was followed up by a double-blind trial, in which 3.2 grams per day of vitamin C was reported to have no protective effect against post-transfusion hepatitis.³²⁵ (However, in the latter trial, vitamin C actually reduced the incidence of hepatitis by 29%, although this reduction was not statistically significant.) An older trial suggested that injections of vitamin C may be helpful in treating viral hepatitis.³²⁶

Vitamin C has been shown to inhibit HIV replication in test tubes.³²⁷ Intake of vitamin C by HIV-positive persons may be associated with a reduced risk of progression to AIDS.³²⁸ Some doctors recommend large amounts of vitamin C for people with AIDS. Reported benefits in preliminary research include greater resistance against infection and an improvement in overall well-being.³²⁹ The amount of vitamin C used in that study ranged from 40 to 185 grams per day. Supplementation with such large amounts of vitamin C must be monitored by a doctor. This same researcher also reports some success in using a topical vitamin C paste to treat herpes simplex outbreaks and Kaposi’s sarcoma in people with AIDS.

In theory, high amounts of vitamin C might help people with hives by lowering histamine levels.³³⁰ Amounts of at least 2,000 mg daily appear necessary to produce these effects.³³¹ No research trials have yet explored the clinical effects of vitamin C supplementation in people with hives.

Five double-blind trials have found that vitamin C supplementation reduces blood pressure, but the reduction was statistically significant in only three of the five, and in most cases reductions were modest.^{332 , 333} Some doctors recommend that people with elevated blood pressure supplement with 1,000 mg vitamin C per day.

Research has shown that supplementing with chromium (200 mcg per day)³³⁴ or magnesium (340 mg per day)³³⁵ 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.³³⁶ Other nutrients, including vitamin C, vitamin E, zinc, copper, manganese, and vitamin B6, may help control blood sugar levels in diabetics.³³⁷ 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.

According to a review of clinical trials, the combination of beta-carotene and vitamin E has led to complete or partial remissions in six of eight trials studying people with leukoplakia.³³⁸ In one trial, administration of 50,000 IU of beta-carotene, 1 gram of vitamin C, and 800 IU of vitamin E per day for nine months led to improvement in 56% of people with leukoplakia, with stronger effects in those who also stopped using tobacco and alcohol.³³⁹ In a double-blind trial, a group of men with leukoplakia was given a combination of vitamin A (100,000 IU per week), beta-carotene approximately 67,000 IU per day), and vitamin E (80 IU per week).³⁴⁰ A 38% decrease in the incidence of leukoplakia was observed after six months of treatment.

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.³⁴¹ No controlled research has been done to examine this claim further.

Sunlight triggers oxidative damage in the eye, which in turn can cause macular degeneration.³⁴² Animals given antioxidants—which protect against oxidative damage—have a lower risk of this vision problem.³⁴³ People with high blood levels of antioxidants also have a lower risk.³⁴⁴ Those with the highest levels (top 20th percentile) of the antioxidants selenium, vitamin C, and vitamin E may have a 70% lower risk of developing macular degeneration, compared with people with the lowest levels of these nutrients (bottom 20th percentile).³⁴⁵ People who eat fruits and vegetables high in beta-carotene, another antioxidant, are also at low risk.³⁴⁶ Some doctors recommend antioxidant supplements to reduce the risk of macular degeneration; reasonable adult levels include 200 mcg of selenium, 1,000 mg of vitamin C, 400 IU of vitamin E, and 25,000 IU of natural beta-carotene per day. However, a preliminary study found no association between age-related macular degeneration and intake of antioxidants, either from the diet, from supplements, or from both combined.³⁴⁷ Moreover, in a double-blind study of male cigarette smokers, supplementing with vitamin E (50 IU per day), synthetic beta-carotene (about 33,000 IU per day), or both did not reduce the incidence of age-related macular degeneration.³⁴⁸

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.³⁴⁹ 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.

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.³⁵⁰ In another study, 70% of women with excessive menstrual bleeding experienced at least a 50% reduction in bleeding after taking a flavonoid product.³⁵¹ 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.

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.³⁵² 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.

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.

Test tube studies have shown that vitamin C inhibits the growth of E.coli, ³⁵³ the most common cause of ABP and CBP. Results from preliminary human studies indicate vitamin C supplementation can cause changes in urine composition that may inhibit the growth of urinary E. coli. ^{354 , 355} Although vitamin C has not been studied in bacterial prostatitis, the association of this condition with urinary tract infections leads many nutritionally oriented doctors to recommend its use, in the form of ascorbic acid, for bacterial prostatitis due to E. coli infection.

Antioxidant nutrients protect the body’s cells from oxygen-related damage. Many studies show that sickle cell anemia patients tend to have low blood levels of antioxidants, including carotenoids, vitamin A, vitamin E, and vitamin C, despite adequate intake.^{356, 357, 358, 359, 360, 361} Low blood levels of vitamin E in particular have been associated with higher numbers of diseased cells in children³⁶² and with greater frequency of symptoms in adults.³⁶³ A small, preliminary trial reported a 44% decrease in the average number of diseased cells in six sickle cell anemia patients given 450 IU vitamin E per day for up to 35 weeks. This effect was maintained as long as supplementation continued.³⁶⁴

In another preliminary trial, 13 patients with sickle cell anemia were given two supplement combinations for seven to eight months each. The first combination included 109 mg zinc, 153 IU vitamin E, 600 mg vitamin C, and 400 ml (about 14 ounces) of soybean oil containing 11 grams of linoleic acid and 1.5 grams of alpha linolenic acid. The second combination included 140 IU vitamin E, 600 mg vitamin C, and 20 grams of fish oil containing 6 grams of omega-3 fatty acids. Reduction in diseased cells was observed only during the administration of the first protocol. The authors concluded that zinc was the important difference between the two combinations and may be a protector of red blood cell membranes.³⁶⁵

Fish oil alone has also been studied. In a double-blind trial, supplementation with menhaden oil, in the amount of 250 mg per 2.2 pounds of body weight per day for one year, reduced the frequency of severe pain episodes by approximately 45%, compared with placebo.³⁶⁶ This treatment may work by correcting an imbalance between omega-3 and omega-6 fatty acids that occurs in people with sickle cell anemia.³⁶⁷

Histamine is associated with increased nasal and sinus congestion. In one study, vitamin C supplementation (1,000 mg three times per day) reduced histamine levels in people with either high histamine levels or low blood levels of vitamin C.³⁶⁸ Another study found that 2,000 mg of vitamin C helped protect people exposed to a histamine challenge test.³⁶⁹ Not every study reported reductions in histamine.³⁷⁰ Although preliminary evidence supports the use of vitamin C when injected into the sinuses of people suffering with acute sinusitis, the effect of oral vitamin C on symptoms of sinusitis has yet to be formally studied.³⁷¹

During a ten-year period, doctors at the North Nassau Mental Health Center in New York treated approximately 11,000 people with schizophrenia with a megavitamin regimen that included vitamin C (up to 4 grams per day), vitamin B3—either as niacin or niacinamide—(up to 4 grams per day), vitamin B6 (up to 800 mg per day), and vitamin E (up to 1,200 IU per day). During that time, not a single new case of TD was seen, even though many of the people were taking neuroleptic drugs.³⁷² Another psychiatrist who routinely used niacinamide, vitamin C, and vitamin B-complex over a 28-year period rarely saw TD develop in her patients.³⁷³ Further research is needed to determine which nutrients or combinations of nutrients were most important for preventing TD. The amounts of niacinamide and vitamin B6 used in this research may cause significant side effects and may require monitoring by a doctor.

A clinical report describes the use of vitamin supplements in the treatment of vitiligo.³⁷⁷ Folic 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.³⁷⁸ This combined regimen was more effective than either vitamin supplementation or sun exposure alone.