Vitamin C, Cancer, and Kidney Stones, Part II

Vitamin C

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin. Unlike most mammals and other animals, humans do not have the ability to make their own vitamin C. Therefore, we must obtain vitamin C through our diet.

Function

Vitamin C is required for the synthesis of collagen, an important structural component of blood vessels, tendons, ligaments, and bone. Vitamin C also plays an important role in the synthesis of the neurotransmitter, norepinephrine. Neurotransmitters are critical to brain function and are known to affect mood. In addition, vitamin C is required for the synthesis of carnitine, a small molecule that is essential for the transport of fat into cellular organelles called mitochondria, where the fat is converted to energy (1). Research also suggests that vitamin C is involved in the metabolism of cholesterol to bile acids, which may have implications for blood cholesterol levels and the incidence of gallstones (2).

Vitamin C is also a highly effective antioxidant. Even in small amounts vitamin C can protect indispensable molecules in the body, such as proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA), from damage by free radicals and reactive oxygen species that can be generated during normal metabolism as well as through exposure to toxins and pollutants (e.g., cigarette smoke). Vitamin C may also be able to regenerate other antioxidants such as vitamin E (1). One recent study of cigarette smokers found that vitamin C regenerated vitamin E from its oxidized form (3).

Role in Immunity

Vitamin C affects several components of the human immune system; for example, vitamin C has been shown to stimulate both the production  and function  of leukocytes (white blood cells), especially neutrophils, lymphocytes, and phagocytes. Specific measures of functions stimulated by vitamin C include cellular motility,   chemotaxis , and phagocytosis.  Neutrophils, which attack foreign bacteria and viruses, seem to be the primary cell type stimulated by vitamin C, but lymphocytes and other phagocytes are also affected ). Additionally, several studies have shown that supplemental vitamin C increases serum levels of antibodies  and C1q complement proteins  guinea pigs, which—like humans—cannot synthesize vitamin C and hence depend on dietary vitamin C. However, some studies have reported no beneficial changes in leukocyte production or function with vitamin C treatment. Vitamin C may also protect the integrity of immune cells. Neutrophils, mononuclear phagocytes, and lymphocytes accumulate vitamin C  to high concentrations, which can protect these cell types from oxidative damage.  In response to invading microorganisms, phagocytic leukocytes release non-specific toxins, such as superoxide radicals, hypochlorous acid (“bleach”), and peroxynitrite; these reactive oxygen species kill pathogens and, in the process, can damage the leukocytes themselves. Vitamin C, through its antioxidant functions, has been shown to protect leukocytes from such effects of autooxidation. Phagocytic leukocytes also produce and release cytokines, including interferons, which have antiviral activity. Vitamin C has been shown to increase interferon levels in vitro.

It is widely thought by the general public that vitamin C boosts the function of the immune system, and accordingly, may protect against viral infections and perhaps other diseases. While some studies suggest the biological plausibility of vitamin C as an immune enhancer, human studies published to date are conflicting. Further, controlled clinical trials of appropriate statistical power would be necessary to determine if supplemental vitamin C boosts the immune system.

Food Sources of Vitamin C

As shown in the table below, different fruits and vegetables vary in their vitamin C content, but five servings (2½ cups) of fruits and vegetables should average out to about 200 mg of vitamin C. If you wish to check foods for their nutrient content, search the USDA food composition database.

Food                                     Serving                 Vitamin C (mg)
Orange juice                  ¾ cup (6 ounces)                62-93
Grapefruit juice              ¾ cup (6 ounces)                62-70
Orange                              1 medium                           70
Grapefruit                        ½ medium                             38
Strawberries                   1 cup, whole                          85
Tomato                             1 medium                             16
Sweet red pepper         ½ cup, raw chopped               95
Broccoli                            ½ cup, cooked                       51
Potato                               1 medium, baked                 17

Vitamin C Supplements

Vitamin C (L-ascorbic acid) is available in many forms, but there is little scientific evidence that any one form is better absorbed or more effective than another. Most experimental and clinical research uses ascorbic acid or sodium ascorbate.

Natural vs. synthetic vitamin C

Natural and synthetic L-ascorbic acid are chemically identical and there are no known differences in their biological activities or bioavailabilities

Kidney Stones

Because oxalate is a metabolite of vitamin C, there is some concern that high vitamin C intake could increase the risk of oxalate kidney stones. Some, but not all, studies have reported that supplemental vitamin C increases urinary oxalate levels. Whether any increase in oxalate levels would translate to an elevation in risk for kidney stones has been examined in epidemiological studies. Two large prospective studies, one following 45,251 men for six years and the other following 85,557 women for 14 years, reported that consumption of ≥1,500 mg of vitamin C daily did not increase the risk of kidney stone formation compared to those consuming <250 mg daily. However, a more recent prospective study that followed 45,619 men for 14 years found that those who consumed ≥1,000 mg/day of vitamin C had a 41% higher risk of kidney stones compared to men consuming <90 mg of vitamin C daily—the current recommended dietary allowance (see RDA). In this study, low intakes (90-249 mg/day) of vitamin C (primarily from the diet) were also associated with a significantly elevated risk. Supplemental vitamin C intake was only weakly associated with increased risk of kidney stones in this study. Despite conflicting results, it may be prudent for individuals predisposed to oxalate kidney stone formation to avoid high-dose vitamin C supplementation.

Linus Pauling Institute Recommendations

For healthy men and women, the Linus Pauling Institute recommends a vitamin C intake of at least 400 mg daily—the amount that has been found to fully saturate plasma and circulating cells with vitamin C in young, healthy nonsmokers. Consuming at least five servings (2½ cups) of fruits and vegetables daily provides about 200 mg of vitamin C. Most multivitamin supplements provide 60 mg of vitamin C. To make sure you meet the Institute’s recommendation, supplemental vitamin C in two separate 250-mg doses taken in the morning and evening is recommended.

Older adults (65 years and older)

Although it is not yet known with certainty whether older adults have higher requirements for vitamin C than younger people, some older populations have been found to have vitamin C intakes considerably below the RDA of 75 and 90 mg/day for women and men, respectively. A vitamin C intake of at least 400 mg daily may be particularly important for older adults who are at higher risk for chronic diseases. In addition, a meta-analysis of 36 publications examining the relationship between vitamin C intake and plasma concentrations of vitamin C concluded that older adults (age 60-96 years) have considerably lower plasma levels of vitamin C following a certain intake of vitamin C compared with younger individuals (age 15-65 years), suggesting that older adults may have higher vitamin C requirements. Studies conducted at the National Institutes of Health indicated that plasma and circulating cells in healthy, young subjects attain maximal concentrations of vitamin C at a dose of about 400 mg/day—a dose much higher than the current RDA. Pharmacokinetic studies in older adults have not yet been conducted, but evidence suggests that the efficiency of one of the molecular mechanisms for the cellular uptake of vitamin C declines with age. Because maximizing blood levels of vitamin C may be important in protection against oxidative damage to cells and biological molecules, a vitamin C intake of at least 400 mg daily is particularly important for older adults who are at higher risk for chronic diseases caused, in part, by oxidative damage, such as heart disease, stroke, certain cancers, and cataract.

References:

1.  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(6):1086-1107.

2.  Simon JA, Hudes ES. Serum ascorbic acid and gallbladder disease prevalence among US adults: the Third National Health and Nutrition Examination Survey (NHANES III). Arch Intern Med. 2000;160(7):931-936.

3.  Bruno RS, Leonard SW, Atkinson J, et al. Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radic Biol Med. 2006;40(4):689-697.

4. Kennes B, Dumont I, Brohee D, Hubert C, Neve P. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerontology. 1983;29(5):305-310

5.   U.S. Department of Agriculture, Agricultural Research Service. USDA National Nutrient Database for Standard Reference, Release 22. 2009. Available at: http://www.nal.usda.gov/fnic/foodcomp/search/. Accessed 11/7/09.

6.  Michels AJ, Joisher N, Hagen TM. Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes. Arch Biochem Biophys. 2003;410(1):112-120