Vitamin C Reduces Human Mortality

Humans do not internally produce vitamin C.

Diets provide enough vitamin C to avoid scurvy, but nowhere near what may be optimal doses.

Researchers have found that vitamin C promotes a longer lifespan and can help prevent many of the disorders related to aging, including cancer.

In a major new study, people with higher blood levels of vitamin C were at significantly lower risk for heart disease and cancer death—and were up to 25% less likely to die from any cause.¹

Vitamin C shows potential to significantly improve the quality of life.

Effect of Vitamin C on Mortality

In a new study, researchers examined vitamin C blood levels and their relationship with patients' health.¹

The study involved 948 randomly selected, healthy men and women aged 53 to 84, whose blood was collected in 1999-2000.¹ Subjects were closely followed for the next 16 years, and their health was tracked.

What the study showed was that people whose 16-year-old blood samples contained the highest levels of vitamin C back then had significantly lower risks of dying now.¹

The differences were dramatic. Those in the highest quartile of baseline blood vitamin C levels were 25% less likely to die than those in the lowest quartile.¹

Finally, when the researchers analyzed data by disease type, they found that those in the top quartile of blood vitamin C levels in 1999-2000 were at a lower risk for both heart disease and cancer deaths 16 years later.¹

Many other studies also show a clear link between vitamin C and leading a long, healthy life.

While higher vitamin C levels are associated with people who practice healthier behavior patterns, this study nonetheless shows striking reductions in mortality rates in those with the highest blood levels of vitamin C.

Boosting Longevity

Animal studies show that vitamin C can reverse several age-related abnormalities in tissues. This includes reducing inflammatory responses, protecting DNA integrity, and reducing biomarkers of cellular stress. When left unaddressed, all of these are associated with rapid aging.^2-5

Research demonstrates that vitamin C supplementation can extend lifespan in a primitive worm often used in longevity testing.⁵

Studies in mice show even more dramatic results. Humans are among the very few mammals not capable of making their own vitamin C and so they must obtain it from their diet. Scientists did a series of studies using mice that were genetically engineered to age prematurely and require dietary vitamin C.^2-4

These studies found that in the absence of significant dietary vitamin C, the mice have a severe reduction in lifespan, and have numerous metabolic abnormalities that resemble those of older humans.^2-4

But when vitamin C is added to their diet, the animals' lifespans were significantly increased, and all metabolic abnormalities were resolved.^2-4

The evidence is clear: Vitamin C is an important component to healthy longevity. The results are even more remarkable when scientists examine the role of vitamin C in specific diseases that cause premature death in humans.

Vitamin C and Cancer

Vitamin C is powerful in reducing the oxidative stress that can trigger DNA damage, leading to cancer initiation, and it can inhibit the inflammatory response that promotes tumor growth.^6,7

Taking vitamin C supplements reduces markers of oxidative stress in non-smokers exposed to second-hand smoke. Vitamin C supplements have also been shown to reduce damage to human cells that was caused by exposure to radiation.^6,8

In fact, some recent studies recommend vitamin C and other antioxidants as ideal protection for patients before undergoing imaging studies that use radiation (like X-rays and CT scans).⁸

The vitamin may act directly on developing malignancies as well. Vitamin C can generate hydrogen peroxide, which destroys rapidly-replicating cancer cells.^7,9

Gastrointestinal cancers are among the most common and most preventable malignancies.

A large clinical study found that higher vitamin C levels were strongly linked to a lower risk of stomach cancer (gastric adenocarcinoma). For each 0.35 mg/dL increase in blood levels of vitamin C, there was a 14% reduction in risk of this tumor. Compared to people with the lowest vitamin C levels, those with normal concentrations had an overall 27% reduction in stomach cancer risk.¹⁰

Breast cancer studies show a similar result: Women with the highest intake of vitamin C prior to a cancer diagnosis were 25% less likely to die from the disease compared to those with the lowest levels.¹¹

In experiments with normal mice and those genetically engineered to express human genes (including lack of vitamin C synthesis), all normal animals developed mammary cancers after implantation with human breast cancer cells. In mice bearing human genes there was a reduced growth when given modest vitamin C supplementation. Moreover, in the engineered mice on higher-dose vitamin C, none developed tumors. ¹²

Vitamin C Adds Cardio Protection

Research into vitamin C and cardiovascular disease has shown that the vitamin can act at multiple pathways involved in the development of atherosclerosis, arterial blockage, and the resulting heart attacks and strokes.

Lipid peroxidation, free radical damage to fats, is a crucial step in the development of atherosclerosis and heart disease. Studies show that vitamin C at doses of 1,000 mg per day lowers levels of oxidative-stress markers in blood, even during the high oxidative-stress period following a meal.^6,13

Vitamin C has shown many beneficial effects in preventing cardiovascular disease:

• Vitamin C preserved crucial cardiac stem cells, required for healing damaged heart tissue, in a lab study.¹⁴
• Two grams per day of vitamin C fully restored an important cardiovascular repair system in smokers after just 2 weeks of supplementation, giving them the same healing capacity as non-smokers.¹⁵
• A meta-analysis of 44 clinical trials showed that vitamin C supplementation improved endothelial function. The effect was stronger in those with higher cardiovascular risk.¹⁶
• Vitamin C reduces the tendency to form harmful plaque and clots. A modest 500 mg per-day dose for 3 months in overweight and obese subjects triggered the release of a natural clot-busting protein, tissue plasminogen activator (tPA) in endothelial cells.¹⁷
• A human double-blind study found that vitamin C supplementation for 6 weeks resulted in a 37% reduction in the numbers of monocytes sticking to endothelial cells—reducing the risk that atherosclerotic plaque would form.¹⁸
• A clinical study of older men showed that a dietary intervention to increase vitamin C levels slowed the progression in thickening of the carotid artery.¹⁹

The overall impact of vitamin C on cardiovascular disease risk is potentially life-saving, and studies suggest that daily supplementation with ample amounts can optimize protection of the heart and major arteries.

Boost Immune Function, Cut Infection Risk

Vitamin C is especially beneficial to the immune system, helping to prevent viral respiratory infections like the common cold.^20,21 Immune system cells accumulate vitamin C, using it to create chemical "weapons" which destroy invading bacteria and viruses.^22,23

Diminished levels of vitamin C leave us vulnerable to specific disease-causing microbes.²¹

Vitamin C's immune-boosting effects arise from multiple mechanisms:^21,22,24-27

• Promoting the actions of phagocytes, the cellular "eating machines" that chew up bacterial and fungal cells.
• Activating T-cells, white blood cells, that scan the body for abnormalities and infections and direct both antibody-producing cells and killer cells to work against viruses and bacteria.
• Mitigating oxidative stress and reducing unneeded inflammatory responses.

In addition, vitamin C slows the gradual shrinkage of the thymus gland in mice.²⁵ A shrinking thymus is closely associated with immunosenescence, in which a declining immune system leaves older people at higher risk for infection and autoimmune disorders.²⁸

A meta-analysis of 7 randomized, controlled trials found that, at the onset of an upper respiratory tract infection such as a cold, the addition of doses greater than one gram of vitamin C per day, on top of an ongoing daily preventive vitamin C regimen, significantly shortened the duration of illness and the severity of symptoms.²⁹

Bone Health

Large population studies have found that higher vitamin C intake is associated with greater bone mass, and that lower vitamin C intake correlates with bone loss.³⁰ And clinical studies have shown positive associations between vitamin C supplementation and improved bone mineral density.^31-33

A 2018 systematic review and meta-analysis found that overall, greater vitamin C intake was associated with a 33% lower risk of osteoporosis, a lower risk of hip fractures, and greater bone mineral density.³⁴ This isn't surprising, given that vitamin C is required by enzymes that produce the protein matrix in bones. Thus, vitamin C is required for healthy, strong bones.³¹

The study used mice with genetic defects that make them reliant on dietary vitamin C, as humans are. Multiple bone abnormalities were uncovered when the animals were fed a C-deficient diet. However, when vitamin C supplements were given, those abnormalities were resolved.^30,35-37

Vitamin C has a tremendous impact on bone, including restoring normal development of critical bone-forming cells (osteoblasts).³⁸

May Help Boost Mood, Fight Depression

Clinical studies are revealing that supplemental vitamin C, alone or in combination with anti-anxiety drugs, improves mood-related disorders.

In a randomized, controlled trial, two weeks of vitamin C treatment reduced anxiety compared to a placebo.⁴⁸ In another controlled, clinical trial, 6 weeks of supplementation with vitamin C at a dosage of 1,000 mg daily significantly reduced anxiety levels.⁴⁹

Another placebo-controlled clinical trial in children with major depression found that with the addition of vitamin C to fluoxetine drug therapy the children had lower depression scores than those who received the fluoxetine plus a placebo.⁵⁰ Remarkably, a short-term trial found that a single dose of 1,000 mg of vitamin C significantly reduced anxiety, compared to baseline levels, among the subjects in the top one-quarter of anxiety scores.⁵¹

Several mechanisms are being explored to explain vitamin C's mood-improving effects — beyond its ability to combat oxidative stress. One recent animal study showed that vitamin C may activate receptors for the neurotransmitter GABA, which boosts mood.⁵¹ Another provided evidence that vitamin C modulates human opioid-like receptors as it exerts its anti-depressant effects.⁵²

Summary

Multiple, large studies have shown that individuals with higher blood levels of vitamin C are less likely to die from any cause. Vitamin C has important preventive effects on a range of age-associated disorders.

Studies show that vitamin C supplementation can help prevent many kinds of cancers, protect the heart and blood vessels, boost the immune system and fight immune senescence. It has even shown the ability to help prevent osteoporosis and promote healthy bone formation.

Daily vitamin C supplementation plays a vital role in optimizing our body's ability to combat oxidative stress and protect against many of the diseases associated with aging.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

1. Wang SM, Fan JH, Taylor PR, et al. Association of plasma vitamin C concentration to total and cause-specific mortality: a 16-year prospective study in China. J Epidemiol Community Health. 2018 Dec;72(12):1076-82.
2. Aumailley L, Dubois MJ, Brennan TA, et al. Serum vitamin C levels modulate the lifespan and endoplasmic reticulum stress response pathways in mice synthesizing a nonfunctional mutant WRN protein. FASEB J. 2018 Jul;32(7):3623-40.
3. Aumailley L, Warren A, Garand C, et al. Vitamin C modulates the metabolic and cytokine profiles, alleviates hepatic endoplasmic reticulum stress, and increases the life span of Gulo-/- mice. Aging (Albany NY). 2016 Mar;8(3):458-83.
4. Son YS, Ullah HMA, Elfadl AK, et al. Preventive Effects of Vitamin C on Diethylnitrosamine-induced Hepatotoxicity in Smp30 Knockout Mice. In Vivo. 2018 Jan-Feb;32(1):93-9.
5. Dallaire A, Proulx S, Simard MJ, et al. Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span. BMC Genomics. 2014 Oct 27;15:940.
6. Dietrich M, Block G, Benowitz NL, et al. Vitamin C supplementation decreases oxidative stress biomarker f2-isoprostanes in plasma of nonsmokers exposed to environmental tobacco smoke. Nutr Cancer. 2003;45(2):176-84.
7. Du J, Cullen JJ, Buettner GR. Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim Biophys Acta. 2012 Dec;1826(2):443-57.
8. Velauthapillai N, Barfett J, Jaffer H, et al. Antioxidants Taken Orally prior to Diagnostic Radiation Exposure Can Prevent DNA Injury. J Vasc Interv Radiol. 2017 Mar;28(3):406-11.
9. Vissers MCM, Das AB. Potential Mechanisms of Action for Vitamin C in Cancer: Reviewing the Evidence. Front Physiol. 2018;9:809.
10. Lam TK, Freedman ND, Fan JH, et al. Prediagnostic plasma vitamin C and risk of gastric adenocarcinoma and esophageal squamous cell carcinoma in a Chinese population. Am J Clin Nutr. 2013 Nov;98(5):1289-97.
11. Harris HR, Bergkvist L, Wolk A. Vitamin C intake and breast cancer mortality in a cohort of Swedish women. Br J Cancer. 2013 Jul 9;109(1):257-64.
12. Cha J, Roomi MW, Kalinovsky T, et al. Lipoprotein(a) and vitamin C impair development of breast cancer tumors in Lp(a)+; Gulo-/- mice. Int J Oncol. 2016 Sep;49(3):895-902.
13. Mazloom Z, Hejazi N, Dabbaghmanesh MH, et al. Effect of vitamin C supplementation on postprandial oxidative stress and lipid profile in type 2 diabetic patients. Pak J Biol Sci. 2011 Oct 1;14(19):900-4.
14. Sumanasekera WK, Dao HT, Shekhovtsova V, et al. The mechanistic role of oxidative stress in cigarette smoke-induced cardiac stem cell dysfunction and prevention by ascorbic acid. Cell Biol Toxicol. 2018 Jul 13.
15. Stadler N, Eggermann J, Voo S, et al. Smoking-induced monocyte dysfunction is reversed by vitamin C supplementation in vivo. Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):120-6.
16. Ashor AW, Lara J, Mathers JC, et al. Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials. Atherosclerosis. 2014 Jul;235(1):9-20.
17. Van Guilder GP, Hoetzer GL, Greiner JJ, et al. Acute and chronic effects of vitamin C on endothelial fibrinolytic function in overweight and obese adult humans. J Physiol. 2008 Jul 15;586(14):3525-35.
18. Woollard KJ, Loryman CJ, Meredith E, et al. Effects of oral vitamin C on monocyte: endothelial cell adhesion in healthy subjects. Biochem Biophys Res Commun. 2002 Jun 28;294(5):1161-8.
19. Ellingsen I, Seljeflot I, Arnesen H, et al. Vitamin C consumption is associated with less progression in carotid intima media thickness in elderly men: A 3-year intervention study. Nutr Metab Cardiovasc Dis. 2009 Jan;19(1):8-14.
20. Gorton HC, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther. 1999 Oct;22(8):530-3.
21. Strohle A, Hahn A. [Vitamin C and immune function]. Med Monatsschr Pharm. 2009 Feb;32(2):49-54; quiz 5-6.
22. Strohle A, Wolters M, Hahn A. Micronutrients at the interface between inflammation and infection--ascorbic acid and calciferol: part 1, general overview with a focus on ascorbic acid. Inflamm Allergy Drug Targets. 2011 Feb;10(1):54-63.
23. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov 3;9(11).
24. Manning J, Mitchell B, Appadurai DA, et al. Vitamin C promotes maturation of T-cells. Antioxid Redox Signal. 2013 Dec 10;19(17):2054-67.
25. Uchio R, Hirose Y, Murosaki S, et al. High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice. Br J Nutr. 2015 Feb 28;113(4):603-9.
26. Chen Y, Luo G, Yuan J, et al. Vitamin C mitigates oxidative stress and tumor necrosis factor-alpha in severe community-acquired pneumonia and LPS-induced macrophages. Mediators Inflamm. 2014;2014:426740.
27. de la Fuente M, Ferrandez MD, Burgos MS, et al. Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol. 1998 Apr;76(4):373-80.
28. Bauer ME, Wieck A, Petersen LE, et al. Neuroendocrine and viral correlates of premature immunosenescence. Ann N Y Acad Sci. 2015 Sep;1351:11-21.
29. Ran L, Zhao W, Wang J, et al. Extra Dose of Vitamin C Based on a Daily Supplementation Shortens the Common Cold: A Meta-Analysis of 9 Randomized Controlled Trials. Biomed Res Int. 2018;2018:1837634.
30. Zhu LL, Cao J, Sun M, et al. Vitamin C prevents hypogonadal bone loss. PLoS One. 2012;7(10):e47058.
    
31. Hall SL, Greendale GA. The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int. 1998 Sep;63(3):183-9.
32. Chuin A, Labonte M, Tessier D, et al. Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study. Osteoporos Int. 2009 Jul;20(7):1253-8.
33. Ruiz-Ramos M, Vargas LA, Fortoul Van der Goes TI, 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 Jun;14(6):467-72.
34. Malmir H, Shab-Bidar S, Djafarian K. Vitamin C intake in relation to bone mineral density and risk of hip fracture and osteoporosis: a systematic review and meta-analysis of observational studies. Br J Nutr. 2018 Apr;119(8):847-58.
35. Park JK, Lee EM, Kim AY, et al. Vitamin C deficiency accelerates bone loss inducing an increase in PPAR-gamma expression in SMP30 knockout mice. Int J Exp Pathol. 2012 Oct;93(5):332-40.
36. Lai CW, Chen HL, Tu MY, et al. A novel osteoporosis model with ascorbic acid deficiency in Akr1A1 gene knockout mice. Oncotarget. 2017 Jan 31;8(5):7357-69.
37. Nishijima K, Ohno T, Amano A, et al. Bone Degeneration and Its Recovery in SMP30/GNL-Knockout Mice. J Nutr Health Aging. 2017;21(5):573-8.
38. Gabbay KH, Bohren KM, Morello R, et al. Ascorbate synthesis pathway: dual role of ascorbate in bone homeostasis. J Biol Chem. 2010 Jun 18;285(25):19510-20.
39. Findik RB, Ilkaya F, Guresci S, et al. Effect of vitamin C on collagen structure of cardinal and uterosacral ligaments during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2016 Jun;201:31-5.
40. Panwar P, Butler GS, Jamroz A, et al. Aging-associated modifications of collagen affect its degradation by matrix metalloproteinases. Matrix Biol. 2018 Jan;65:30-44.
41. Wilson S, Guilbert M, Sulé-Suso J, et al. The effect of collagen ageing on its structure and cellular behavior. Vol 82222012.
42. DePhillipo NN, Aman ZS, Kennedy MI, et al. Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review. Orthop J Sports Med. 2018 Oct;6(10):2325967118804544.
43. Kavitha O, Thampan RV. Factors influencing collagen biosynthesis. J Cell Biochem. 2008 Jul 1;104(4):1150-60.
44. Murad S, Grove D, Lindberg KA, et al. Regulation of collagen synthesis by ascorbic acid. Proc Natl Acad Sci U S A. 1981 May;78(5):2879-82.
45. Schwarz RI, Bissell MJ. Dependence of the differentiated state on the cellular environment: modulation of collagen synthesis in tendon cells. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4453-7.
46. Kawashima S, Funakoshi T, Sato Y, et al. Protective effect of pre- and post-vitamin C treatments on UVB-irradiation-induced skin damage. Sci Rep. 2018 Nov 1;8(1):16199.
47. Jeong JH, Kim MB, Kim C, et al. Inhibitory effect of vitamin C on intrinsic aging in human dermal fibroblasts and hairless mice. Food Sci Biotechnol. 2018 Apr;27(2):555-64.
48. de Oliveira IJ, de Souza VV, Motta V, et al. Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial. Pak J Biol Sci. 2015 Jan;18(1):11-8.
49. Mazloom Z, Ekramzadeh M, Hejazi N. Efficacy of supplementary vitamins C and E on anxiety, depression and stress in type 2 diabetic patients: a randomized, single-blind, placebo-controlled trial. Pak J Biol Sci. 2013 Nov 15;16(22):1597-600.
50. Amr M, El-Mogy A, Shams T, et al. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013 Mar 9;12:31.
51. Moritz B, Schwarzbold ML, Guarnieri R, et al. Effects of ascorbic acid on anxiety state and affect in a non-clinical sample. Acta Neurobiol Exp (Wars). 2017;77(4):362-72.
52. Rosa PB, Neis VB, Ribeiro CM, et al. Antidepressant-like effects of ascorbic acid and ketamine involve modulation of GABAA and GABAB receptors. Pharmacol Rep. 2016 Oct;68(5):996-1001.