Vitamin C

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The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Vitamin C has in your body, and how strong these effects are.

Level of Evidence	Effect	Change	Magnitude of Effect Size	Scientific Consensus	Comments
B	General Oxidation		Minor	50% See all 6 studies	Surprisingly mixed influences on biomarkers of oxidation, with either a decrease or no significant influence the majority of the time (with limited evidence to hint at... show an increase being possible)
B	Blood Flow		Minor	100% See all 4 studies	An increase in blood flow is seen in instances of impaired blood flow (smoking, obesity, etc.) which may be due to preservation of nitric oxide function (via reducing oxidation... show thereof); this is a phenomena general to antioxidants and not unique to Vitamin C
B	Inflammation			100% See all 4 studies	No significant alterations seen in inflammatory cytokines associated with Vitamin C supplementation
B	Muscle Damage		Minor	50% See all 4 studies	Although not acute, a possible reduction in biomarkers of muscle damage is sometimes noted with antioxidative supplementation which applies to Vitamin C; results are unreliable
B	Cortisol		Minor	66% See all 4 studies	1g of Vitamin C taken prior to exercise is associated with unreliable reductions in the cortisol spike seen during exercise
B	Exercise-induced Immune Suppression			66% See all 3 studies	More evidence suggests no significant effect than a possible protective effect, although the latter is possible
B	Protection from Smoking			66% See all 3 studies	There do not appear to be any inherent protective effects of Vitamin C against the oxidative and inflammatory changes associated with cigarette smoking, although the reduction... show in blood flow may be attenuated somewhat with antioxidants and this applies to Vitamin C
C	Glycemic control			100% See study	No significant influence on glycemic control in diabetics with Vitamin C supplementation
C	Triglycerides			100% See 2 studies	No significant influence on fasting or postprandial triglycerides seems apparent with Vitamin C
C	Lipid Peroxidation		Minor	50% See all 4 studies	Mixed and weak influences on lipid peroxidation, but a possible reduction exists
C	Heart Palpitations			100% See study	No significant influence on heart palpitations
C	Symptoms of Bacterial Vaginosis		Minor	100% See study	Vaginal bacterial infections are somewhat treatable with directly applied (via silicon coated tablets), as Vitamin C exerts some antioxidant effects against those bacterial strains
C	Microcirculation		Minor	100% See study	An increase in microcirculation has been noted secondary to increased blood flow, thought to be a general property of antioxidants
C	Fat Mass			100% See study	Does not appear to significantly influence fat mass
C	Weight			100% See 2 studies	Vitamin C does not appear to have a weight reducing effect
C	Adaptations to Exercise		Minor	50% See 2 studies	It is thought that, secondary to reducing the rate of muscular damage, that adaptations gained from exercise are attenuated; there is mixed evidence to support this, but... show is seems possible with antioxidants
C	VO2 max			100% See study	Does not appear to have a role in altering VO2 max
C	Aerobic exercise			100% See all 3 studies	No significant influence on aerobic exercise performance
C	Total Cholesterol			100% See 2 studies	No significant influence on total cholesterol seems apparent with vitamin C supplementation
C	Symptoms of Charcot-Marie-Tooth Disease			100% See study	Insufficient evidence to support a role
C	Insulin Sensitivity			100% See study	No significant influence on insulin sensitivity
C	Pre-Eclampsia Risk			100% See study	No significant influence on pre-eclampsia risk
C	Risk of Cataracts			100% See study	No significant influence on the risk of cataracts
C	Spontaneous Birth Risk			100% See study	No significant influence on spontaneous birthing
C	Upper Respiratory Tract Infection Risk			100% See 2 studies	No significant influence on the rate of acquiring sickness
C	Length of Sickness			50% See 2 studies	Mixed influences on the length one is sick for, with possibly no effect
C	Subjective Well-being		Minor	100% See study	An improvement in mood has been noted in hospitalized persons
C	Bone Mineral Density		Minor	100% See 2 studies	The rate of bone mineral density loss over time in elder women appears to be reduced with dietary antioxidants, and as such applies to Vitamin C supplementation. The protective... show effect is not remarkably large
C	Anti-oxidant Enzyme Profile		Minor	100% See study	An increase in antioxidant enzymes have been noted in elderly persons
C	C-Reactive Protein		Minor	100% See study	A possible reduction in C-Reactive Protein exists with Vitamin C supplementation
C	DNA damage			100% See 2 studies	No significant influences on DNA damage
C	Exercise-induced Oxidation			0% See 2 studies	Highly mixed interactions with the exercise:oxidation axis with Vitamin C, with both increases and decreases being noted. Unlikely to have a reliable role
C	Muscle Soreness		Minor	100% See study	A possible reduction in muscle soreness the day after exercise may result when preloading exercise with Vitamin C
C	HbA1c			100% See study	No significant influence of Vitamin C supplementation on HbA1c levels
C	Oxidation of LDL			100% See 2 studies	No significant influence on the oxidation rates of LDL cholesterol
C	HDL-C			100% See study	No significant influence on HDL cholesterol
C	LDL-C			100% See study	No significant alterations in LDL cholesterol seen with Vitamin C supplementation
C	Heart Rate		Minor	100% See study	A decrease in heart rate has been noted in exercising obese adults, a per se effect of Vitamin C on heart rate (rather than secondary to the rate of percieved exertion)... show seems unlikely.
C	Rate of Percieved Exertion		Minor	100% See study	The rate of percieved exertion in obese adults appears to be attenuated with Vitamin C supplementation
C	Fatigue		Minor	100% See study	A decrease in fatigue has been noted in obese adults given Vitamin C in conjunction with exercise
C	Fat Oxidation			100% See study	No significant influence on fat oxidation
D	Symptoms of Osteoarthritis			100% See study	No significant influence on the symptoms of osteoarthritis

Studies Excluded from Consideration

• Confounded with Vitamin E^[1]

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Edit1. Sources and Structure

1.1. Sources

1.2. Structure

1.3. Supplementation

European regulation state that any supplement with the label 'Vitamin C' may be one of five compounds; L-Ascorbic Acid (actual vitamin C), Sodium-L-Ascorbate, Potassium-L-Ascorbate, Calcium-L-Ascorbate, and L-Ascorbyl-6-Palmitate.^[2] For vitamin-related purposes, they are equipotent. They differ on some parameters such as DNA oxidation where Sodium Ascorbate and Ascorbic Acid could exert pro-oxidative effects on DNA, Calcium Ascorbate acting neutral and Ascorbyl-6-Palmitate being protective.^[3]

Edit2. Related Molecules and Compounds

2.1. Ester-C

Ester-C is a brand name product for Vitamin C that is non-acidic^[4] and consists of Vitamin C metabolites (the aldonic acids L-lyxonic, L-xylonic, and L-threonic acid) with Calcium; labelled as Calcium Ascorbate. Ester-C is more effective in preventing scurvy than basic L-Ascorbic Acid in a deficiency state.^[5] Ester-C is patented by Zila Nutraceuticals.

One pilot study noted that although L-Ascorbic Acid (basic form of vitamin C) and Ester-C were equally potent in increasing serum levels of Vitamin C up to 5 days, the group given L-Ascorbic Acid experienced a decline whereas Ester-C levels remained elevated.^[6]

This particular form of Vitamin C has been implicated in reducing both occurrence and duration of the common cold, but was not compared to L-ascorbic acid.^[7] Another study conducted on oxalate levels in vivo (most common substrate from which kidney stones are formed) found Ester-C more effective than an equal dose of L-Ascorbic Acid when both were dosed at 500mg; 25% more subjects experienced a significant decline in 24-hour oxalate with Ester-C relative to L-ascorbate.^[6][8]

One study suggests that when consuming 1g of Vitamin C, Ester-C is tolerated better due to being non-acidic; this study was conducted in persons with self-reported sensitivity to acid containing foods.^[4] 53.6% of the Vitamin C group experienced gastric upset compared to 14.3% of the Ester-C group, the latter was rated as more tolerable during follow-up.

Studies conducted using Ester-C that have been funded by Zila Nutraceuticals are cited following this sentence.^[4]

Edit3. Neurology

3.1. Dementia

Serum levels of Vitamin C appear to be inversely related with risk of Dementia, with an Odds Ratio (OR) of 0.29 after controlling for school education, intake of dietary supplements, smoking habits, body mass index, and alcohol consumption.^[9]

Edit4. Interactions with Exercise

4.1. Power Output

Vitamin C (400mg), in conjunction with Vitamin E (286mg) as a mixed anti-oxidant supplement for 6 weeks in otherwise healthy men, is not significantly better than placebo at attenuating an exercise-induced reduction of power output seen during the recovery phase of exercise.^[1]

4.2. Obesity and Fatigue

It is generally accepted that the state of obesity, relative to a non-obese state, makes the same amount of exercise more tiring to the body (perception) and uses more caloric reserves for the same amount of work.^[10] Ingestion of 500mg Vitamin C via supplementation when paired with both an exercise regimen and a caloric restriction diet was able to significantly reduce heart rate during exercise and the rate of perceived exertion, although it didn't affect success on the diet.^[11]

4.3. Delayed Onset Muscle Soreness (DOMS)

DOMS is a soreness and tenderness of the muscle tissue that arises after exercise, usually with a delay where it does not suface immediately but usually the next day or 48 hours afterwards.

One study using Vitamin C at 400mg (with Vitamin E at 264mg) failed to notice any benefit to soreness with treatment relative to placebo.^[1]

Edit5. Interactions with Bone Metabolism

5.1. Bone Mass

At least one rat study notes that supplementation with Vitamin C (5mg) is associated with an attenuation of bone loss due to ovariectomy, an animal model of menopause.^[12] After 8 weeks of supplementation, the control ovariectomy group experienced bone loss while the ovariectomy group with Vitamin C was not significantly different than control.^[12]

Edit6. Interactions with Hormones

6.1. Cortisol

An attenuation of exercise-induced cortisol release has been noted in response to mixed Vitamin C/Vitamin E supplementation at 400mg/286mg when measured one hour after exercise, with values pre-exercise and a day later not differing between groups.^[1] This reduction of exercise-induced cortisol elevations have been noted in heat-subjected marathon runners at 1,500mg daily for 12 days prior to exercise.^[13]

At least one study at 60% VO2 max cycling for 2.5 hours in trained athletes found that this attenuation of cortisol to not be statistically significant.^[14]

References

1. Oxidative stress, inflammation and recovery of muscle function after damaging exercise: effect of 6-week mixed antioxidant supplementation
2. Directive 2002/46/EC
3. Bergström T, Bergman J, Möller L. Vitamin A and C compounds permitted in supplements differ in their abilities to affect cell viability, DNA and the DNA nucleoside deoxyguanosine. Mutagenesis. (2011)
4. Gruenwald J, et al. Safety and tolerance of ester-C compared with regular ascorbic acid. Adv Ther. (2006)
5. Verlangieri AJ, Fay MJ, Bannon AW. Comparison of the anti-scorbutic activity of L-ascorbic acid and Ester C in the non-ascorbate synthesizing Osteogenic Disorder Shionogi (ODS) rat. Life Sci. (1991)
6. Moyad MA, et al. Vitamin C with metabolites reduce oxalate levels compared to ascorbic acid: a preliminary and novel clinical urologic finding. Urol Nurs. (2009)
7. Van Straten M, Josling P. Preventing the common cold with a vitamin C supplement: a double-blind, placebo-controlled survey. Adv Ther. (2002)
8. Moyad MA, et al. Vitamin C with metabolites: additional analysis suggests favorable changes in oxalate. Urol Nurs. (2009)
9. Dietary Antioxidants and Dementia in a Population-Based Case-Control Study among Older People in South Germany
10. Ekkekakis P, Lind E. Exercise does not feel the same when you are overweight: the impact of self-selected and imposed intensity on affect and exertion. Int J Obes (Lond). (2006)
11. Huck CJ, et al. Vitamin C status and perception of effort during exercise in obese adults adhering to a calorie-reduced diet. Nutrition. (2012)
12. Zhu LL, et al. Vitamin C prevents hypogonadal bone loss. PLoS One. (2012)
13. Carrillo AE, Murphy RJ, Cheung SS. Vitamin C supplementation and salivary immune function following exercise-heat stress. Int J Sports Physiol Perform. (2008)
14. Davison G, Gleeson M. The effect of 2 weeks vitamin C supplementation on immunoendocrine responses to 2.5 h cycling exercise in man. Eur J Appl Physiol. (2006)
15. Mazloom Z, et al. Effect of vitamin C supplementation on postprandial oxidative stress and lipid profile in type 2 diabetic patients. Pak J Biol Sci. (2011)
16. De Marchi S, et al. Ascorbic acid prevents vascular dysfunction induced by oral glucose load in healthy subjects. Eur J Intern Med. (2012)
17. Khemis A, et al. A randomized controlled study to evaluate the depigmenting activity of L-ascorbic acid plus phytic acid-serum vs. placebo on solar lentigines. J Cosmet Dermatol. (2011)
18. Gomes ME, et al. High dose ascorbic acid does not reverse central sympathetic overactivity in chronic heart failure. J Clin Pharm Ther. (2011)
19. Colby JA, et al. Effect of ascorbic acid on inflammatory markers after cardiothoracic surgery. Am J Health Syst Pharm. (2011)
20. Talaulikar VS, Chambers T, Manyonda I. Exploiting the antioxidant potential of a common vitamin: could vitamin C prevent postmenopausal osteoporosis. J Obstet Gynaecol Res. (2012)
21. Petersen EE, et al. Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial. Arzneimittelforschung. (2011)
22. Stewart JM, Ocon AJ, Medow MS. Ascorbate improves circulation in postural tachycardia syndrome. Am J Physiol Heart Circ Physiol. (2011)
23. Knab AM, et al. Quercetin with vitamin C and niacin does not affect body mass or composition. Appl Physiol Nutr Metab. (2011)
24. Fernandes PR, et al. Vitamin C restores blood pressure and vasodilator response during mental stress in obese children. Arq Bras Cardiol. (2011)
25. Theodorou AA, et al. No effect of antioxidant supplementation on muscle performance and blood redox status adaptations to eccentric training. Am J Clin Nutr. (2011)
26. Roberts LA, et al. Vitamin C consumption does not impair training-induced improvements in exercise performance. Int J Sports Physiol Perform. (2011)
27. Knab AM, et al. Influence of quercetin supplementation on disease risk factors in community-dwelling adults. J Am Diet Assoc. (2011)
28. Pareyson D, et al. Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial. Lancet Neurol. (2011)
29. Yfanti C, et al. Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training. Am J Physiol Endocrinol Metab. (2011)
30. Kuiper HC, et al. Vitamin C supplementation lowers urinary levels of 4-hydroperoxy-2-nonenal metabolites in humans. Free Radic Biol Med. (2011)
31. Kalpdev A, Saha SC, Dhawan V. Vitamin C and E supplementation does not reduce the risk of superimposed PE in pregnancy. Hypertens Pregnancy. (2011)
32. Christen WG, et al. Age-related cataract in a randomized trial of vitamins E and C in men. Arch Ophthalmol. (2010)
33. Lagowska-Lenard M, Stelmasiak Z, Bartosik-Psujek H. Influence of vitamin C on markers of oxidative stress in the earliest period of ischemic stroke. Pharmacol Rep. (2010)
34. Hauth JC, et al. Vitamin C and E supplementation to prevent spontaneous preterm birth: a randomized controlled trial. Obstet Gynecol. (2010)
35. Constantini NW, et al. The effect of vitamin C on upper respiratory infections in adolescent swimmers: a randomized trial. Eur J Pediatr. (2011)
36. Zhang M, et al. Vitamin C provision improves mood in acutely hospitalized patients. Nutrition. (2011)
37. Nazıroğlu M, et al. Vitamins C and E treatment combined with exercise modulates oxidative stress markers in blood of patients with fibromyalgia: a controlled clinical pilot study. Stress. (2010)
38. Ruiz-Ramos M, et al. Supplementation of ascorbic acid and alpha-tocopherol is useful to preventing bone loss linked to oxidative stress in elderly. J Nutr Health Aging. (2010)
39. Ristow M, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. (2009)
40. Chuin A, et al. Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study. Osteoporos Int. (2009)
41. Block G, et al. Vitamin C treatment reduces elevated C-reactive protein. Free Radic Biol Med. (2009)
42. Retana-Ugalde R, et al. High dosage of ascorbic acid and alpha-tocopherol is not useful for diminishing oxidative stress and DNA damage in healthy elderly adults. Ann Nutr Metab. (2008)
43. Nakhostin-Roohi B, et al. Effect of vitamin C supplementation on lipid peroxidation, muscle damage and inflammation after 30-min exercise at 75% VO2max. J Sports Med Phys Fitness. (2008)
44. Ataka S, et al. Effects of Applephenon and ascorbic acid on physical fatigue. Nutrition. (2007)
45. Guarnieri S, Riso P, Porrini M. Orange juice vs vitamin C: effect on hydrogen peroxide-induced DNA damage in mononuclear blood cells. Br J Nutr. (2007)
46. Bryer SC, Goldfarb AH. Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stress to eccentric exercise. Int J Sport Nutr Exerc Metab. (2006)
47. Camargo JL, Stifft J, Gross JL. The effect of aspirin and vitamins C and E on HbA1c assays. Clin Chim Acta. (2006)
48. Davison G, Gleeson M. Influence of acute vitamin C and/or carbohydrate ingestion on hormonal, cytokine, and immune responses to prolonged exercise. Int J Sport Nutr Exerc Metab. (2005)
49. Bryant RJ, et al. Effects of vitamin E and C supplementation either alone or in combination on exercise-induced lipid peroxidation in trained cyclists. J Strength Cond Res. (2003)
50. Fuller CJ, May MA, Martin KJ. The effect of vitamin E and vitamin C supplementation on LDL oxidizability and neutrophil respiratory burst in young smokers. J Am Coll Nutr. (2000)
51. Johnston CS, Dancho CL, Strong GM. Orange juice ingestion and supplemental vitamin C are equally effective at reducing plasma lipid peroxidation in healthy adult women. J Am Coll Nutr. (2003)
52. Kim MK, et al. Long-term vitamin C supplementation has no markedly favourable effect on serum lipids in middle-aged Japanese subjects. Br J Nutr. (2004)
53. Stamatelopoulos KS, et al. Oral administration of ascorbic acid attenuates endothelial dysfunction after short-term cigarette smoking. Int J Vitam Nutr Res. (2003)
54. Thompson D, et al. Prolonged vitamin C supplementation and recovery from eccentric exercise. Eur J Appl Physiol. (2004)
55. Kinlay S, et al. Long-term effect of combined vitamins E and C on coronary and peripheral endothelial function. J Am Coll Cardiol. (2004)
56. Van Hoydonck PG, et al. Does vitamin C supplementation influence the levels of circulating oxidized LDL, sICAM-1, sVCAM-1 and vWF-antigen in healthy male smokers. Eur J Clin Nutr. (2004)
57. Mastaloudis A, et al. Antioxidant supplementation prevents exercise-induced lipid peroxidation, but not inflammation, in ultramarathon runners. Free Radic Biol Med. (2004)

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