1. VITAMINS AND MINERALS Sept 10, 2014 Levine et al: Vitamin C dose and tissue levels

2. DEVELOPING KNOWLEDGE OF VITAMIN C: THE OLD AND THE NEW The older knowledge: Key role in promoting healthy connective tissue, esp collagen Daily intake to prevent scurvy - 20 mg appears to be fully adequate, for most people (exceptions?) High oral doses are excreted, because renal threshold is exceeded Roles in synthesis of stress hormones and carnitine

3. The newer knowledge and controversy: Role as biological antioxidant - NOT SHOWN in animal studies??? Guinea pig studies critical, don’t support the hypothesis Low tissue levels may reflect ILLNESS as well as diet (inflammation may accelerate vitamin C catabolism) Major role in supporting the absorption of dietary iron: will be examined further later this semester High levels are pro-oxidant, and may be useful for cancer treatment.

4. LEVINE ET AL, PNAS, 2001

5. Time course to achieve plateau vitamin C in one subject, given 60 mg of vitamin C/day

6. RELATION BETWEEN VITAMIN C INTAKE AND ACHIEVED PLATEAU AT EACH DOSE

7. FUNCTION OF KIDNEY GLOMERULUS: Fluid from the artery forms the glomerular filtrate, and then many components are reabsorbed back to the bloodstream. ARTERY VEIN URINE Fluid from the plasma: glomerular filtrate contains vitamin C Vitamin C is resorbed by a specific transporter

8. Because many water-soluble nutrients are excreted by the kidney, we will make reference to kidney function many times throughout the semester. The ability of the kidney to release nutrients into the primary filtrate, and then re-absorb most of what was excreted, is basic to the function of the kidney.

9. Dose/response curves for vitamin C in different WBC populations

10. NEUTROPHIL VITAMIN C, AS A FUNCTION OF DOSE: deficiency symptoms unlikely when tissue levels reach 50-75% of the maximum attainable level.

11. Isoprostanes are formed from the peroxidation of highly unsaturated fatty acids. Vitamin C is frequently described as an antioxidant. What conclusions can be reached from this data ?

12. THESE STUDIES ALL POINT TO ONE CONCLUSION: Vitamin C in plasma reaches a maximum at ~100 microMolar, when diet is the source of the vitamin C. You might absorb 1 gram from the diet, but you will excrete much of that promptly in the urine. HOWEVER: If you get sick, processes in the body can degrade stored vitamin C, so we need more information on doses needed for people who are ill. Smokers also need more vitamin C, since cigarette smoke breaks down vitamin C in the lung tissues. LATER IN THE SEMESTER, WHEN WE DISCUSS IRON, WE WILL DISCUSS USE OF VITAMIN C AS A PRO-OXIDANT TO KILL TUMOR CELLS. IT WORKS WITH IRON FOR THIS PURPOSE. THE VITAMIN C IS GIVEN IV, TO REACH VERY HIGH LEVELS IN TISSUES.

13. MARGINAL VITAMIN C STATUS There are many people who have plasma vitamin C in the range of 10-20 microMolar, this is frequently seen in studies of large populations. These people do NOT have clinical scurvy, but would they be healthier with better intake of vitamin C? This question has been discussed for more than 20 years, but has not been resolved. What CLINICAL INDICATORS would indicate that a person was healthier, following increased vitamin C intake? These people do not have major illness, but perhaps in some ways they would be healthier. Some investigators are working on this!