9.3 Vitamin C

Vitamin C

Vitamin C is well-known for being a water-soluble antioxidant. Humans are one of the few mammals that don’t synthesize vitamin C, due to a mutation in our genetic code, making it an essential micronutrient. However, due to the prevalence of vitamin C in human diets, and our ability to efficiently recycle it, deficiencies are uncommon in developed countries1.

Vitamin C’s scientific names are ascorbic acid or ascorbate, and the oxidized (radicalized) form is known as dehydroascorbic acid or dehydroascorbate. The structures of ascorbic acid and dehydroascorbic acid are shown in Figures 9.31 & 9.32.

Figure 9.31 Structure of ascorbic acid2

Figure 9.32 Structure of dehydroascorbic acid3. Notice the change in the two bottom OH groups from Figure 9.31.

Figure 9.33 shows the reaction through which ascorbic acid can stabilize, or quench, 2 free radicals. The 2 circled hydrogens are lost and replaced by double bonds when ascorbic acid is

oxidized to dehydroascorbic acid. Reducing dehydroascorbic acid back to ascorbic acid is the opposite reaction.

Figure 9.33 The oxidation-reduction reaction between ascorbic acid (left) and dehydroascorbic acid (right)2,3

Ascorbic acid is believed to be a part of the antioxidant network we see in the vitamin E section (shown below) where it is oxidized to reduce alpha-tocopherol radicals. Dehydroascorbic acid can be reduced by thioredoxin reductase, a selenoenzyme, to regenerate ascorbic acid.

Figure 9.34 The theorized antioxidant network4

For more information on vitamin C, see the Required Web Link below.

Required Web LinkVitamin C Fact Sheet

Subsections:

• 9.31 Absorption and Tissue Accumulation of Vitamin C
• 9.32 Enzymatic Functions of Vitamin C
• 9.33 Vitamin C Deficiency – Scurvy
• 9.34 Vitamin C Toxicity, Linus Pauling, & the Common Cold

References & Links

• Stipanuk MH. (2006) Biochemical, Physiological, & Molecular Aspects of Human Nutrition. St. Louis, MO: Saunders Elsevier.
• http://en.wikipedia.org/wiki/File:Ascorbic_acid_structure.png
• http://en.wikipedia.org/wiki/File:Dehydroascorbic_acid.png
• Packer L, Weber SU, Rimbach G. (2001) Molecular aspects of alpha-tocotrienol antioxidant action and cell signaling. J Nutr 131(2): 369S-373S.

Links

Vitamin C Fact Sheet – https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/

Vitamin C Absorption & Tissue Accumulation

Vitamin C is found in foods primarily as ascorbic acid (80-90%), but dehydroascorbic acid is also present (10-20%). The bioavailability (amount that enters the bloodstream) of vitamin C is high at lower doses as shown below, but drops to less than 50% at higher doses.

Table 9.311 Bioavailability of vitamin C1

Ascorbic acid is actively absorbed into the enterocyte by the sodium vitamin C cotransporter (SVCT) 1. It then diffuses along its concentration gradient into the bloodstream. Vitamin C generally circulates as ascorbic acid.

Figure 9.311 Ascorbic acid (Asc) absorption

Accumulation

Most water-soluble vitamins, including vitamin C are not stored in the body. However, it does accumulate in certain tissues in the body where its levels can be 5-100x higher than those found in the plasma2. The table below shows the concentrations of vitamin C in different tissues and fluids. Make note of which tissues/fluids have the highest concentrations, and which have the lowest concentrations.

Table 9.312 Human tissue & fluid ascorbic acid concentrations1

* mg/100 g wet tissue, mg/100 mL fluids

References & Links

• Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. (2006) Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins.
• Stipanuk MH. (2006) Biochemical, Physiological, & Molecular Aspects of Human Nutrition. St. Louis, MO: Saunders Elsevier.

Enzymatic Functions of Vitamin C

In addition to its antioxidant function, vitamin C is also a cofactor for a number of enzymes that are important in the formation of the protein collagen.

Why should you care about collagen formation? Because collagen is estimated to account for 30% or more of total proteins in the body2. Collagen contains a number of hydroxylated amino acids that are needed for collagen strands to properly cross-link. This cross-linking is important for collagen to wind together like a rope, forming the strong triple helix known as tropocollagen. This process is shown in the Figure 9.321 below.

Figure 9.321 Production of cross-linked tropocollagen in the presence of adequate vitamin C

But if there isn’t enough ascorbic acid available, the collagen strands are underhydroxylated and instead of forming strong tropocollagen, the underhydroxylated collagen is degraded as shown below.

Figure 9.322 Production of underhydroxylated collagen

This weak collagen then results in the symptoms seen in scurvy that will be discussed in the next subsection.

Ascorbic Acid is also needed for2:

• Carnitine synthesis – plays a critical role in energy production
• Tyrosine synthesis and catabolism – a precursor to synthesis of the neurotransmitters norepinephrine and dopamine
• Serotonin & norepinephrine synthesis – important neurotransmitters in the body
• Adrenal hormone synthesis – responsible for multiple functions including stress management, inflammatory responses, and fight-or-flight responses

References & Links

• Di Lullo G, Sweeney S, Korkko J, Ala-Kokko L, San Antonio J. (2002) Mapping the ligand- binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. The Journal of Biological Chemistry 277(6): 4223-4231.
• Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.

Vitamin C Deficiency (Scurvy)

Why should you care about the functions of vitamin C? Because they explain the symptoms of vitamin C deficiency. While it is rare in the United States, vitamin C deficiency, known as scurvy,

displays symptoms that are a result of weak collagen, that in turn, weakens connective tissue throughout the body. Symptoms of scurvy include bleeding gums, pinpoint hemorrhages, and corkscrew hairs as shown in Figure 9.331 and Required Web Link on the next page.

Figure 9.331 Bleeding gums that occur in scurvy1

Required Web LinkCorkscrew Hairs

Additional symptoms include impaired wound and fracture healing, easy bruising, and loose or decaying teeth. Scurvy can be fatal if not treated. Scurvy was the first discovered nutrition deficiency in 1746 by James Lind, who is shown below3.

Figure 9.332 Dr. James Lind discovered that scurvy was caused by a nutrition deficiency3

Lind was a surgeon on a British navy ship. Frequently during voyages the sailors would develop scurvy for reasons that weren’t understood at the time. It was known that citrus fruits could cure or prevent scurvy, but it was believed this was due to their acidity. Lind performed clinical trials comparing citrus juice to dilute sulfuric acid and vinegar (acetic acid), and found that only citrus juice caused the sailors to recover, indicating that it was something in the citrus juice itself, and not its acidity, that prevented/cured scurvy. This is depicted in the Required Web Link, showing a sailor being treated with a lemon, below. As a result of the discovery, the British sailors became known as “Limeys” because they would drink limejuice to prevent the development of the disease4. The Required Web Link is a good video on this subject.

Required Web LinkVideo: Vitamin C and the Limeys (7:21)

References & Links

• http://en.wikipedia.org/wiki/File:Scorbutic_gums.jpg
• Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.
• http://en.wikipedia.org/wiki/File:James_lind.jpg
• Carpenter K. (2003) A short history of nutritional science: Part 3 (1912-1944). J Nutr 133(10): 638-645.

Links

Corkscrew Hairs – http://www.nlm.nih.gov/medlineplus/ency/imagepages/2345.htm Vitamin C and the Limeys – https://www.youtube.com/watch?v=Mp9II8MmuoA&feature=youtu.be

Vitamin C Toxicity, Linus Pauling & the Common Cold

Vitamin C does not have a toxicity per se, but in some people, over 2 grams/day can lead to diarrhea and gastrointestinal distress. In addition, high supplementation of vitamin C increases the excretion oxalate in urine which may lead to the formation of calcium oxalate in the kidneys1. Calcium oxalate is one of the primary forms of kidney stones. However, a direct link between excretion of oxalate and actual stone formation hasn’t been established1.

Nevertheless, high-dose vitamin C supplementation should be approached with some caution,

since it is not clear whether it increases the risk of forming kidney stones2.

The figures below show the most common sites of pain in someone with kidney stones.

Figure 9.341 Kidney stones normally cause pain in the shaded areas3

The Required Web Links below include a video that describes what kidney stones are, the symptoms of having stones, and some pictures of kidney stones.

Required Web LinksVideo: Kidney Stones (1:16) Kidney Stones

Linus Pauling and the Common Cold

The person who popularized taking mega-doses of vitamin C was Dr. Linus Pauling. Dr. Pauling was a chemist, and is the only person to receive 2 unshared Nobel Prizes. The Nobel Prize is a prestigious award, and Dr. Pauling was close to solving the structure of DNA. This would have likely netted him another Nobel prize, but Watson and Crick beat him to it.

Figure 9.344 Linus Pauling4

Later in his life Pauling became convinced that mega-doses of vitamin C could prevent the common cold. In 1970, his book Vitamin C and the Common Cold was released and became a bestseller. Later he came to believe that vitamin C could prevent cardiovascular disease, cancer, and combat aging5. However, critics of his beliefs countered that all mega-dose supplementation was doing was creating “expensive urine”. This refers to the fact that the RDA is only 75-90 mg/day for adults and Pauling recommended taking 1-2 grams of vitamin C daily6.

Thus, with vitamin C being water-soluble, most of the vitamin C that people on the regimen

were paying to consume was being excreted in the urine, thus making it “expensive”.

A recent review of vitamin C and colds found that that routine mega-doses of vitamin C do not reduce the risk of the common cold in most individuals. However, there is some evidence that it might benefit people exposed to brief periods of severe physical exercise (marathon runners) or cold environments (skiers and soldiers in subarctic conditions). There has been little research conducted in children, so it is not known whether vitamin C supplementation is beneficial in this age group7.

References & Links

• https://www.niddk.nih.gov/health-information/urologic-diseases/kidney-stones
• Massey L, Liebman M, Kynast-Gales S. (2005) Ascorbate increases human oxaluria and kidney stone risk. J Nutr 135(7): 1673-1677.
• https://commons.wikimedia.org/wiki/File:Pos-renal.png
• https://www.flickr.com/photos/oregonstateuniversity/5711642694
• http://lpi.oregonstate.edu/lpbio/lpbio2.html

• http://www.health.harvard.edu/newsletter_article/excerpts_from_vitamin_c_and_the_com mon_cold_by_linus_pauling
• Hemilä H, Chalker E, Douglas B. Vitamin C for preventing and treating the common cold.

Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD000980. DOI: 10.1002/14651858.CD000980.pub3.

Video

Kidney Stones – https://www.youtube.com/watch?v=16ewFJ-iQtw

Links

Kidney Stones – http://www.herringlab.com/photos/index.html