Life Extension Buffered vitamin C (454g)

In 1937, the Nobel Prize in Physiology was awarded to Albert Szent-Gyorgyi for his research on vitamin C. At the time, vitamin C was a rare commodity and could only be extracted from adrenal glands or massive amounts of orange juice.

Szent-Gyorgyi’s discoveries helped launch an onslaught of vitamin C research, especially into its ability to enhance immune function.

The human body does not produce vitamin C. It must be obtained from outside-the-body sources. Water-soluble vitamin C is quickly excreted.1 That’s why it makes sense to supplement daily with vitamin C to ensure the body has the protection it needs.

Aging individuals tend to have lower levels of vitamin C circulating in their blood stream and immune cells.2,3This can lead to impaired immune function.4,5

While vitamin C helps maintain tissue and speed wound healing, an overlooked strength is its impact on boosting immune function. As you will read in this article, people with common diseases have lower vitamin C blood levels than healthy individuals.

With the growing body of data about the role that plant-based nutrients play in healthy aging, we sometimes forget about how much documentation exists in support of vitamin C, a nutrient found in small concentrations in certain plant foods.

New evidence is corroborating what scientists long ago advocated relating to the need for humans to maintain optimal vitamin C status.

The Importance Of Vitamin C

  

Vitamin C deficiency has been associated with frequency and duration of colds, along with immune system defects.6 While colds aren’t usually dangerous in themselves, they can lead to pneumonia and other respiratory diseases, especially for aging individuals.7Colds can be an early indicator of gaps in immune function that could leave one vulnerable to a cascade of serious infections.

A deficiency of vitamin C broadly affects the various key aspects of immune function, which include the innate system we are born with, the adaptive system that develops from infancy to young adulthood, the cells that kill invaders, the cells that coordinate those attacks, and even the production of antibodies that fight known infections.

As a result of vitamin C’s wide-ranging impact on the immune system, a deficiency could leave us vulnerable to infections.5 A weakened immune system caused by low vitamin C levels can make any infection more serious. This danger becomes more ominous in older adults, in whom the phenomenon of immunosenescence(the aging of the immune system) already heightens risk.8

There are multiple causes of insufficient vitamin C. Aging is one major cause of lowered vitamin C levels.2,3The concentration of vitamin C in immune cells decreases with age, partly the result of an increasingly oxidative environment that consumes vitamin C. This can lead to damage to DNA, proteins, and fat molecules needed for normal immune function.4,5

Stress is another major trigger for reducing vitamin C levels, leaving the affected individuals vulnerable to infection at precisely the time that stronger immune support is needed.4,5,9

In some remarkable human findings, low vitamin C blood levels have been associated with a number of common human diseases.5,10 The table below shows higher plasma vitamin C levels in healthy individuals compared to those with serious diseases, most notably cancer and sepsis.

A healthy vitamin C level is considered to be between 61 and 80 micromol/L. Those afflicted with serious diseases have much lower vitamin C levels. It is likely that the inflammation and oxidative stress caused by some of these diseases contributes to this reduced vitamin C since it will rapidly be used up quenching free radicals. It’s also possible that lower levels of vitamin C contributed to the development or progression of some of these disorders.

Why The Immune System Depends On Vitamin C

One of the most important functions of vitamin C is to support and energize the body’s immune system. Immune cells have active vitamin C transporter molecules embedded in their membranes that actively pump the vitamin into the cells when more vitamin C is required.5,11

For example, during times of inflammation or infection, those transporters ramp up their activity to provide sufficient vitamin C to the cells’ inner workings, causing cells to attain levels up to 100-fold that of the plasma level. This is why blood levels of vitamin C drop during times of disease or infection (see Table above).5,11

This can create a potentially vicious cycle in which, just when you need extra vitamin C, your body’s stores are depleted. This also makes it especially important to increase one’s intake of vitamin C when sick.

The content of vitamin C within immune cells is closely related to those cells’ activity, especially in the case of specific cells that engulf and destroy infecting organisms (phagocytes) and of those that recruit, organize, and direct other immune cells (T-lymphocytes).11

Fortunately, you can improve your immune system’s function by supplementing with vitamin C.4,6,8,12 The recommended daily allowance of vitamin C is around 90 mg per day. For optimal immune function, many experts now recommend supplementing with 1 gram (1,000 mg) of vitamin C daily in addition to a diet rich in fruits and vegetables.13

Human studies have shown that this amount of vitamin C can not only reduce the duration and severity of the common cold—but can reduce the incidence of developing a cold as well. Not all common cold studies produce consistent results. This means more than vitamin C alone is needed to combat common colds, such as using the right dose of zinc acetate lozenges as soon as cold symptoms manifest.

WHAT YOU NEED TO KNOW

Vitamin C Supports The Immune System

• Older adults are at ever-increasing risk of serious infections or cancers as their immune systems age.
• An intact immune system relies upon many layers of protection from multiple cell types and a host of immunologically active signaling molecules.
• The function of those specialized cells and molecules is being increasingly found to depend on adequate supplies of vitamin C in the body.
• Roughly 23% of Americans have vitamin C depletion, causing their immune systems to not function properly.44
• Studies show that doses of vitamin C at 1,000 mg per day can effectively restore function to myriad components of the immune system.
• New studies confirm that vitamin C supplementation at 1,000 mg per day shortens the duration and mitigates the severity of colds, while also preventing colds from developing, especially in those with low vitamin C levels.
• Take a 1,000 mg per day supplement to optimize your immunity and potentially lengthen your life.

Reduce The Duration And Severity Of Colds

One of the best-known uses of vitamin C is in the prevention and treatment of the common cold.14 While for young people a cold is little more than a nuisance, in older adults, colds can herald the onset of serious bacterial infections such as pneumonia or bronchitis, both of which increase the risk of premature death.

There is no shortage of research demonstrating that vitamin C can reduce symptoms and shorten duration of the common cold.4,15 Studies show that vitamin C supplementation can reduce the duration of colds by anywhere from 5 to 21%. 15

Vitamin C supplementation has also been shown to significantly reduce the severity of cold symptoms. And in older people who require hospitalization for pneumonia and chronic bronchitis, even a dose of just 200 mg per day was shown to reduce the clinical severity of the illness.4

EMERGING AREAS OF VITAMIN C IMPORTANCE IN HUMAN HEALTH

This article primarily considered the role of vitamin C in supporting the immune system, particularly in aging or stressed individuals. There is growing support, however, for use of vitamin C in these other areas as well:

• Diabetes: Diabetes induces powerful oxidant stress throughout the body, leading to inflammation and loss of function. Studies now show that vitamin C status may influence the incidence of type II diabetes, the accelerated cognitive decline of diabetics, the anxiety, depression, and stress experienced by diabetics, and the risk of atrial fibrillation in diabetics.45-48
• Cardiovascular disease: Heart disease and stroke have many causes, but oxidant damage and inflammation lead the pack.49-53 Studies now show vitamin C improves endothelial function (function of the active lining of blood vessels that controls blood flow and pressure) and potentially other areas of cardiovascular medicine.54-56
• Anemia: There is evidence from animal studies that vitamin C can prevent the kind of anemia that arises from excessive iron, which can be seen in older adults. 57
• Periodontal disease: Bleeding gums and tooth loss were common symptoms of scurvy that were readily reversed with vitamin C supplementation. Today’s scientists are demonstrating a role of vitamin C in preventing less obvious, but still important causes of tooth loss in older adults, such as gingivitis.58
• Osteoporosis: Vitamin C is an absolute requirement for normal formation of bone proteins, and preliminary studies are showing the potential of the vitamin in preventing bone loss and fractures related to osteoporosis.59,60

Vitamin C Reduces Incidence Of Colds

While the evidence demonstrating the ability of vitamin C to reduce the duration and the severity of colds is clear, the question of whether vitamin C supplementation could also reduce the incidence (rate of occurrence) of colds has been fiercely debated.16 Newer studies using higher doses of vitamin C show that vitamin C can, in fact, reduce the incidence of colds.

Studies using 1,000 mg or more have shown that vitamin C reduces cold incidence by a remarkable 50%among people undergoing heavy stress, such as soldiers and athletes.4,15,17 These studies found that the people who had the lowest dietary intake of vitamin C had the greatest benefit.

In 2014, a study of vitamin C published in the journal Nutrients provided definitive evidence that vitamin C supplementation can reduce the incidence of the common cold in otherwise healthy people with chronic stress or obesity.6 The study included 18- to 35-year-old men who had vitamin C levels of less than 45 micromol/L(61 to 80 is considered adequate). The study lasted eight weeks, and scientists recorded scores on a physical activity scale and tracked the occurrence of cold episodes.

During the study, 85% of placebo recipients experienced a cold compared with just 47% of supplemented subjects, a statistically significant difference and a risk reduction of 45%.6

Reduction in cold duration was also significant in the supplemented versus the control group, with supplemented subjects experiencing an average of 3.2 (59%) fewer days with cold symptoms than placebo subjects. Intriguingly, supplemented subjects’ physical activity scores also rose by 40% compared with placebo recipients, strongly suggesting that supplementation was correcting hidden symptoms of vitamin C depletion, such as fatigue and malaise.

Even more impressive, at least three controlled studies also show that vitamin C supplementation can reduce the incidence of pneumonia by as much as 80%.15 This is a crucial finding for older adults since the death rate for elderly people with pneumonia exceeds 16%, even with antibiotic treatment, highlighting the urgency of prevention.18,19

Vitamin C And Immunity: Details From Laboratory Studies

The aging of the immune system (immunosenescence) can leave older individuals vulnerable to infection and disease that wouldn’t be an issue for younger people.20 Laboratory studies indicate that vitamin C can restore an aging immune system to that of younger individuals.

An abundance of laboratory studies show that vitamin C can boost immune function, particularly in older people. One particular study demonstrates this perfectly. White blood cells from elderly people typically perform poorly in response to stimulation by foreign material (antigens). However, a study published in theInternational Journal of Immunopharmacology showed that incubating these white blood cells overnight in a solution enriched with vitamin C restored the performance levels of these cells to that of normal cells from younger people.8

In fact, vitamin C produces beneficial effects on virtually all of the immune system’s cells.

• Natural killer (NK) cells. These “hit men” of the immune system move in on infectious and malignant targets that have been identified as foreign by other immune system components. Like other immune cells, NK cells’ function declines with aging.21 Detailed scientific studies show that NK function improves in the presence of adequate vitamin C, and declines without it.22-24 Vitamin C helps NK cells track and destroy tumor cells as well by reducing the shielding effect of platelets (blood clotting cell fragments) that would prevent NK cells from destroying them. This effect may help to prevent cancers from producing deadly metastases.23
• Neutrophils are the main immune system cell for fighting bacterial infections. Neutrophils engulf invading organisms, then destroy them with powerful blasts of short-lived oxygen free radicals. Vitamin C supports many aspects of neutrophil function, aiding in their ability to chase down bacterial targets and improving their ability to engulf and kill such targets.25,26 Since the bacterial killing process creates potent oxidation products, neutrophils would destroy themselves in short order without ample vitamin C, which scavenges up the dangerous oxidizing molecules once they have done their work to destroy the bacterial cell.25-27 
  A study published in the Canadian Journal of Physiology and Pharmacology showed that when human volunteers took an oral dose of 1,000 mg or more of vitamin C, neutrophils performed more vigorously than those of unsupplemented subjects.28 
  Improved function of neutrophils in the presence of adequate vitamin C is so evident that clinicians have begun to use vitamin C at 1,000 mg per day doses for people with chronic granulomatous disease, a disorder in which neutrophils lack proper killing ability once they have ingested bacteria.26,29 Similar improvements in neutrophil performance have been shown in the much larger population of people with asthma, another condition in which neutrophil impairment can worsen patients’ clinical status.26
• Lymphocytes are immune system cells that produce antibodies (called B-lymphocytes) and coordinate with other immune cells to guide them towards threats needing destruction.8,30 When they detect such an incipient threat, lymphocytes rapidly reproduce in a proliferative response that is enhanced in the presence of vitamin C. In older adults, that proliferation is impaired, but vitamin C treatment restores them to youthful levels of function.8,31 Similar enhancements of lymphocyte proliferation have been demonstrated by supplementing aging laboratory animals with vitamin C, which also boosts lymphocytes’ ability to track down threats.32 
  Diabetes, like aging, impairs the production of lymphocytes and the functioning of T-lymphocytes.33,34However, supplementing diabetic rats with vitamin C pushed lymphocyte production from 57% of that of controls to virtually 100% of control values, essentially creating “nondiabetic” immune cells within a living diabetic body.35
• Antibodies are noncellular components of the immune system that help identify and destroy invading threats and cancerous cells.36 Vitamin C benefits this portion of the immune system by raising levels of three main classes of antibody immunoglobulins: IgA, which protects against infections mainly on mucosal surfaces, such as the respiratory and digestive tracts, IgG, which provides long-term protection in the bloodstream, and IgM, which is the earliest immunoglobulin to appear in blood in response to threats.37-40Blood levels of antibodies and other protective molecules rose significantly when volunteers took 1,000 mgdoses of vitamin C daily for 75 days, demonstrating the effect in humans.41

Human Studies Confirm Vitamin C’s Immune Benefits

  

There is now copious evidence that vitamin C benefits people with impaired immune function, whether that impairment is the result of disease or simply of aging.

In patients with frequent skin infections, for example, who had known impairment inneutrophil tracking and killing of microorganisms, vitamin C was as effective as a powerful immune-regulating drug, levamisole, at improving neutrophil function and producing long-lasting remission.42 But unlike levamisole, which produced severe side effects causing 8% of subjects to drop out of the study, no patients in the vitamin C arm dropped out. Similar improvements in neutrophil function, and dramatic clinical recoveries, were seen in patients with recurrent furunculosis (boils), on a dose of 1,000 mg per day.43

This same dose of vitamin C was found to boost immune cell functions in women who were an average of 72 years old.28 In this study, lymphocyte and neutrophil function improved in all members of this group, including those who were healthy, those with major depression, and those with coronary heart disease. This study demonstrated the far-reaching effects of vitamin C in the aging body.

Summary

Few people realize the importance of having ample supplies of water-soluble vitamin C in their body.

Without regular ingestion, ascorbic acid (vitamin C) levels drop rapidly and can produce hidden effects, long before major signs of scurvy appear. Otherwise unexplained fatigue, malaise, or “mind fog” may in reality be symptoms of vitamin C depletion.

All major immune system cell lines function at their peak with ample vitamin C supplies. With inadequate intake or plasma levels, those cells are less able to detect, track, and kill invading organisms or precancerous cells. That means that vitamin C depletion can leave one vulnerable to dangerous infections.

New studies are helping to confirm that vitamin C supplementation can reduce duration and severity of the most prevalent respiratory infection, the common cold, and makes it less likely one will catch a cold in the first place.

Given the health risks associated with adults who develop pneumonia after a cold, prevention with adequatevitamin C (1,000 mg and higher daily doses) looks more promising. This dose, greater than what can fit into most multi-nutrient formulas, will assure you are obtaining sufficient vitamin C to emulate studies documenting improved immune function, protection against the common cold, and other age-related disorders.

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

References

1. Padayatty SJ, Katz A, Wang Y, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003 Feb;22(1):18-35.
2. Van der Loo B, Bachschmid M, Spitzer V, Brey L, Ullrich V, Luscher TF. Decreased plasma and tissue levels of vitamin C in a rat model of aging: implications for antioxidative defense. Biochem Biophys Res Comm. 2003 Apr 4;303(2):483-7.
3. Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes--reversal with (R)-alpha-lipoic acid supplementation. FASEB J. 1998 Sep;12(12):1183-9.
4. Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50(2):85-94.
5. Pavlovic V. A short overview of vitamin C and selected cells of the immune system. Cent. Eur. J. Med.2010 October;8(1):1-10.
6. Johnston CS, Barkyoumb GM, Schumacher SS. Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: a randomized controlled trial. Nutrients. 2014 Jul;6(7):2572-83.
7. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063028/. Accessed August 26, 2015.
8. Delafuente JC, Prendergast JM, Modigh A. Immunologic modulation by vitamin C in the elderly. Int J Immunopharmacol. 1986;8(2):205-11.
9. Berger TM, Polidori MC, Dabbagh A, et al. Antioxidant activity of vitamin C in iron-overloaded human plasma. J Biol Chem. 1997 Jun 20;272(25):15656-60.
10. McGregor GP, Biesalski HK. Rationale and impact of vitamin C in clinical nutrition. Curr Opin Clin Nutr Metab Care. 2006 Nov;9(6):697-703.
11. 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.
12. Mikirova N, Hunninghake R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit.2014;20:725-32.
13. Deruelle F, Baron B. Vitamin C: is supplementation necessary for optimal health? J Altern Complement Med. 2008 Dec;14(10):1291-8.
14. Van Straten M, Josling P. Preventing the common cold with a vitamin C supplement: a double-blind, placebo-controlled survey. Advan Ther. 2002 May-Jun;19(3):151-9.
15. Hemila H, Douglas RM. Vitamin C and acute respiratory infections. Int J Tuberc Lung Dis. 1999 Sep;3(9):756-61.
16. Hemila H. Does vitamin C alleviate the symptoms of the common cold?--a review of current evidence.Scand J Infect Dis. 1994;26(1):1-6.
17. Hemila H. Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress. Int J Sports Med. 1996 Jul;17(5):379-83.
18. Falcone M, Russo A, Cangemi R, et al. Lower mortality rate in elderly patients with community-onset pneumonia on treatment with aspirin. J Am Heart Assoc. 2015;4(1).
19. Ruiz LA, Zalacain R, Capelastegui A, et al. Bacteremic pneumococcal pneumonia in elderly and very elderly patients: host- and pathogen-related factors, process of care, and outcome. J Gerontol A Biol Sci Med Sci. 2014 Aug;69(8):1018-24.
20. Deleidi M, Jaggle M, Rubino G. Immune aging, dysmetabolism, and inflammation in neurological diseases.Front Neurosci. 2015;9:172.
21. Hazeldine J, Lord JM. The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev. 2013 Sep;12(4):1069-78.
22. Heuser G, Vojdani A. Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: the role of protein kinase-C. Immunopharmacol Immunotoxicol. 1997 Aug;19(3):291-312.
23. Toliopoulos IK, Simos YV, Daskalou TA, Verginadis, II, Evangelou AM, Karkabounas SC. Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by administration of ascorbic acid. Indian J Exp Biol. 2011 Dec;49(12):904-8.
24. Kim JE, Cho HS, Yang HS, et al. Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model. Immunobiology. 2012 Sep;217(9):873-81.
25. Leibovitz B, Siegel BV. Ascorbic acid, neutrophil function, and the immune response. Int J Vitam Nutr Res.1978;48(2):159-64.
26. Anderson R. Effects of ascorbate on normal and abnormal leucocyte functions. Int J Vitam Nutr Res Suppl. 1982;23:23-34.
27. Caldefie-Chezet F, Walrand S, Moinard C, Tridon A, Chassagne J, Vasson MP. Is the neutrophil reactive oxygen species production measured by luminol and lucigenin chemiluminescence intra or extracellular? Comparison with DCFH-DA flow cytometry and cytochrome c reduction. Int J Clic Chem. 2002 May 7;319(1):9-17.
28. De la Fuente M, Ferrandez MD, Burgos MS, Soler A, Prieto A, Miquel J. Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol. 1998 Apr;76(4):373-80.
29. Patrone F, Dallegri F, Bonvini E, Minervini F, Sacchetti C. Effects of ascorbic acid on neutrophil function. Studies on normal and chronic granulomatous disease neutrophils. Acta Vitaminol Enzymol. 1982;4(1-2):163-8.
30. Available at: http://www.ncbi.nlm.nih.gov/books/NBK27118/. Accessed August 26, 2015.
31. Kennes B, Dumont I, Brohee D, Hubert C, Neve P. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerontology. 1983;29(5):305-10.
32. Alvarado C, Alvarez P, Jimenez L, De la Fuente M. Improvement of leukocyte functions in young prematurely aging mice after a 5-week ingestion of a diet supplemented with biscuits enriched in antioxidants. Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1203-10.
33. DeFuria J, Belkina AC, Jagannathan-Bogdan M, et al. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5133-8.
34. Martinez PJ, Mathews C, Actor JK, et al. Impaired CD4+ and T-helper 17 cell memory response to Streptococcus pneumoniae is associated with elevated glucose and percent glycated hemoglobin A1c in Mexican Americans with type 2 diabetes mellitus. J Lab Clin Med. 2014 Jan;163(1):53-63.
35. Ozerkan D, Ozsoy N, Cebesoy S. Response of thymus lymphocytes to streptozotocin-induced diabetes and exogenous vitamin C administration in ratsdagger. Microscopy (Oxf). 2014 Dec;63(6):409-17.
36. Schwartz-Albiez R. Naturally occurring antibodies directed against carbohydrate tumor antigens. Adv Exp Med Biol. 2012;750:27-43.
37. Corthesy B. Multi-faceted functions of secretory IgA at mucosal surfaces. Front Immunol. 2013;4:185.
38. Available at: http://www.ncbi.nlm.nih.gov/books/NBK27162/. Accessed August 26, 2015.
39. Wang JP, Kim HJ, Chen YJ, et al. Effects of delta-aminolevulinic acid and vitamin C supplementation on feed intake, backfat, and iron status in sows. J Anim Sci. 2009 Nov;87(11):3589-95.
40. Wang A, Xie F, Wang YH, Wu JL. Effects of vitamin C supplementation on growth performance and antioxidant status of layer ducklings. J Anim Physiol Anim Nutr (Berl). 2011 Aug;95(4):533-9.
41. Prinz W, Bortz R, Bregin B, Hersch M. The effect of ascorbic acid supplementation on some parameters of the human immunological defence system. Int J Vitam Nutr Res. 1977;47(3):248-57.
42. Rebora A, Dallegri F, Patrone F. Neutrophil dysfunction and repeated infections: influence of levamisole and ascorbic acid. Br J Dermatol. 1980 Jan;102(1):49-56.
43. Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F. Vitamin C for the treatment of recurrent furunculosis in patients with imparied neutrophil functions. J Infect Dis. 1996 Jun;173(6):1502-5.
44. Hampl JS, Taylor CA, Johnston CS. Vitamin C deficiency and depletion in the United States: the Third National Health and Nutrition Examination Survey, 1988 to 1994. Am J Pub Health. 2004 May;94(5):870-5.
45. Garcia-Bailo B, El-Sohemy A, Haddad PS, et al. Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress. Biologics. 2011;5:7-19.
46. Harding AH, Wareham NJ, Bingham SA, Khaw K, Luben R, Welch A, Forouhi NG. Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer--Norfolk prospective study. Archives Int Med. 2008 Jul 28;168(14):1493-9.
47. Dakhale GN, Chaudhari HV, Shrivastava M. Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: a randomized, double-blind study. Adv Pharmacol Sce. 2011;2011:195271.
48. Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. 2007 Nov;126(5):471-4.
49. Rodrigo R, Fernandez-Gajardo R, Gutierrez R, Matamala JM, Carrasco R, Miranda-Merchak A, Feuerhake W. Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities.CNS Neurol Disord Drug Targets. 2013 Aug;12(5):698-714.
50. Elkind MS. Princeton Proceedings: Inflammatory Mechanisms of Stroke. Stroke. 2010;41(10 Suppl):S3-S8.
51. Black PH, Garbutt LD. Stress, inflammation and cardiovascular disease. J Psychom Res. 2002 Jan;52(1):1-23.
52. Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hyperten.2000 Jun;18(6):655-73.
53. Csanyi G, Miller FJ, Jr. Oxidative stress in cardiovascular disease. Int J Molec Sci. 2014;15(4):6002-8.
54. Ashor AW, Lara J, Mathers JC, Siervo M. 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.
55. Shaik-Dasthagirisaheb YB, Varvara G, Murmura G, et al. Role of vitamins D, E and C in immunity and inflammation. J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2):291-5.
56. Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011 Sep 1;51(5):1000-13.
57. Chaturvedi R, Chattopadhyay P, Banerjee S, et al. Iron-rich drinking water and ascorbic acid supplementation improved hemolytic anemia in experimental Wistar rats. Int J Food Sci Nutr. 2014 Nov;65(7):856-61.
58. Alagl AS, Bhat SG. Ascorbic acid: New role of an age-old micronutrient in the management of periodontal disease in older adults. Geriatr Gerontol Int. 2014 Nov 19.
59. Finck H, Hart AR, Jennings A, Welch AA. Is there a role for vitamin C in preventing osteoporosis and fractures? A review of the potential underlying mechanisms and current epidemiological evidence. Nutr Res Rev. 2014 Nov 21:1-16.
60. Ruiz-Ramos M, Vargas LA, Fortoul Van der Goes TI, Cervantes-Sandoval A, Mendoza-Nunez VM. 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.