VITAMINS AND MINERALSSept 10, 2014

Levine et al: Vitamin C doseand tissue levels

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

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.

LEVINE ET AL, PNAS, 2001

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

RELATION BETWEEN VITAMIN C INTAKE AND ACHIEVED PLATEAU AT EACH DOSE

FUNCTION OF KIDNEY GLOMERULUS:Fluid from the artery forms the glomerular

filtrate, and then many components arereabsorbed back to the bloodstream.

ARTERY

VEIN

URINE

Fluid from the plasma:glomerular filtratecontains vitamin C

Vitamin C is resorbed by a specific transporter

Because many water-soluble nutrients are excretedby the kidney, we will make reference to kidneyfunction many times throughout the semester.

The ability of the kidney to release nutrients into theprimary filtrate, and then re-absorb most of whatwas excreted, is basic to the function of the kidney.

Dose/response curves for vitamin C in different WBC populations

NEUTROPHIL VITAMIN C, AS A FUNCTION OF DOSE:deficiency symptoms unlikely when tissue levels reach50-75% of the maximum attainable level.

Isoprostanes are formed from the peroxidation ofhighly unsaturated fatty acids.

Vitamin C is frequently described as an antioxidant.What conclusions can be reached from this data?

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 excretemuch of that promptly in the urine.

HOWEVER: If you get sick, processes in the body can degradestored vitamin C, so we need more information on dosesneeded for people who are ill.

Smokers also need more vitamin C, since cigarette smokebreaks 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.

MARGINAL VITAMIN C STATUS

There are many people who have plasma vitamin C inthe range of 10-20 microMolar, this is frequently seen instudies of large populations.

These people do NOT have clinical scurvy, but wouldthey 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 personwas healthier, following increased vitamin C intake?These people do not have major illness, but perhaps in someways they would be healthier.

Some investigators are working on this!