An article from _Contemporary Pediatrics_, June 2006

*What’s the evidence on treating disease with vitamin C and megavitamins?*
_by Sandra F. Braganza, MD, MPH, Philip O. Ozuah, MD, PhD_

A classic example of the use of food to treat disease, absent understanding of how the components in these foods acted, is the British Navy’s use of citrus fruit to prevent scurvy during the late 18th century—more than 100 years before vitamin C was identified as the protective micronutrient. Not until 1912 was the word “vitamin” defined in dictionaries as “organic substances in food essential for chemical processes in the body.” In 1970, the use of vitamin supplementation for a variety of conditions was popularized in a book _Vitamin C and the common cold_, written by Nobel Prize-winning chemist, Linus Pauling.

Vitamins are, simply, compounds necessary for the function, growth, and maintenance of tissue. These compounds act as cofactors for enzymes, which catalyze cellular metabolic reactions. Most vitamins are obtained from food or supplements; exceptions are vitamin D, which is activated by ultraviolet light on skin, and vitamin K, which can be manufactured by bacteria in the gut. The 13 recognized essential vitamins are either fat soluble or water soluble. The fat-soluble vitamins A, D, E and K are stored in body fat and used as needed, whereas excess amounts of water-soluble vitamins C, B, B1, B2, B3, B5, B6, B12, folic acid, and biotin are excreted in the urine.

The use of vitamins is common, and the use of high-dose vitamins—known as megavitamin supplementation—is reported to be the sixth most common form of alternative therapy. Researchers studying the use of alternative medicine in children in Washington, D.C., found that of children who used alternative medicine, 53% used vitamin C; 26%, vitamin A; 19%, vitamin B; and 13%, an antioxidant. A study of alternative therapies in adolescents found that megavitamins were used by 22%. In this article, we discuss the use of two common vitamin supplementations: vitamin C and megavitamins.

*Vitamin C*
Americans obtain approximately 90% of their intake of vitamin C (ascorbic acid) from fruits and vegetables; particularly good sources include kiwi, mango, papaya, pineapple, citrus, broccoli, spinach, cabbage, peppers, and yams. The amount of micronutrient obtained in a given item may be influenced by growing conditions and maturity or ripeness, duration of storage before consumption, and cooking method. Table 1 provides a snapshot of estimated vitamin C content in common foods. Vitamin C is also widely available in syrup, capsule, and tablet form—including chewable, effervescent, and extended-release tablets. The concentration of vitamin C in these formulations varies.

The National Academy of Sciences’s recommended dietary allowance (RDA) is the daily dietary intake sufficient to meet the individual nutrient requirements of at least 97% of individuals of a given age and gender. The RDA of vitamin C for children and adults is shown in Table 2.

Vitamin C is involved in many biochemical actions and is necessary for wound healing, strengthening blood vessel walls, and helping the body use carbohydrate, fat, and protein. Because of its broad involvement, it has been suggested that vitamin C has a role in the treatment and prevention of several conditions, particularly asthma and upper respiratory infections (URIs).

*Asthma*
The role of nutrition in preventing asthma is controversial. It has been proposed that diet and nutrition—particularly antioxidant vitamins—play a role in the rising incidence of asthma. Vitamin C, an antioxidant that is abundant in the extracellular fluid that lines the lung, can convert oxidative insults such as inhaled and infectious agents that are potential asthma triggers, thereby decreasing their adverse effects. Thus, it is thought that a low level of vitamin C is associated with pulmonary dysfunction.

The Third National Health and Nutrition Examination Survey (NHANES III) found that children who have a low vitamin C level have a greater risk of asthma, even when confounders such as socioeconomic status, weight, smoke exposure, urban environment, and ethnicity are taken into account. Although these findings suggest that vitamin C supplementation can reverse or ameliorate the symptoms of asthma, further research has yielded conflicting evidence. A cross-sectional study found that infrequent consumption of fruits with high vitamin C content in children was associated with reduced lung function, whereas a meta-analysis of vitamin C supplementation for the treatment of asthma found insufficient evidence to recommend a specific role for vitamin C in treatment. The research is limited regarding the dosage of vitamin C to improve symptoms of asthma, and further research is needed, including randomized, controlled trials in children, to evaluate the role of vitamin C in asthma.

*Upper respiratory infection*
The role of vitamin C in the prevention and treatment of URI remains debatable. The leading advocate for high-dosage vitamin C intake was, as noted, Pauling, who reported that a daily dose of 1 to 3 g of vitamin C would halve the incidence of URI and greatly reduce the overall severity of infections. Although the results of a 2003 meta-analysis of the literature do not support long-term use of vitamin C supplementation to prevent URI, some data do show that 1,000 g/day of vitamin C during an acute infection diminishes symptoms of URI and shortens the course of illness. Limited studies in children have also demonstrated similar improvements, but additional, carefully designed trials in children are needed to more fully explore the effects of vitamin C supplementation.

*Megavitamin therapy for ADHD?*
The use of vitamins in amounts usually more than 10 times greater than the RDA also was popularized by Pauling. His theory of orthomolecular psychiatry—that certain nutrient deficiencies caused brain dysfunction—led him to recommend the use of megavitamins for many different conditions, including schizophrenia, alcoholism, and depression. We focus this discussion on the use of megavitamins for children with attention-deficit hyperactivity disorder (ADHD).

Megavitamin therapy was used during the 1980s to treat learning disorders and ADHD; early studies showed improved behavior and school performance in subjects. A double-blind placebo-controlled, crossover study of a combination of vitamin B6, niacinamide, vitamin C, and calcium pantothenate, however, demonstrated that, not only did the behavior of children on the megavitamin protocol not improve, but the subjects were, as measured, 25% more disruptive than the control group. Further research is needed to clarify any role for megavitamins in the management of ADHD.

We must also consider the potential adverse effects of megavitamins; case reports have identified episodes of vitamin A intoxication in children and adults; sensory neuropathy secondary to high doses of vitamin B6; fatal hypermagnesemia from unsupervised use of high doses of magnesium oxide administered as part of a regimen of megavitamins to a child with mental retardation; spastic quadriplegia; and seizures. These reports, together with other known toxic effects of megavitamins, such as elevated liver enzyme levels, has led to discontinuation of megavitamins for conditions such as ADHD and learning disorders.

In short, what is the bottom line?
First, there is no clear evidence that long-term daily vitamin C supplementation prevents asthma or a URI—although high-dosage vitamin C during the course of a URI may have some benefit. Second, there is no evidence of a beneficial effect of megavitamins in ADHD.