A Better Form of Vitamin C
By Steven Cortez
Even though humans cannot synthesize vitamin C, every tissue and cell in our body needs this nutrient for healthy growth and repair.1,2
Maintaining optimal levels of vitamin C is difficult because it is water soluble and cannot be stored in the body.3 This inability to maintain high vitamin C levels is recognized by researchers as limiting its potential benefit, especially with regard to chronic illness.4
For years, scientists have been looking for ways to boost the impact of each dose of vitamin C. Fortunately, a method has been discovered to increase the speed at which vitamin C is absorbed.5 Reaching peak concentrations faster offers the edge your body needs to optimize its exposure to vitamin C following each dose.
Maximizing Your Vitamin C
Two botanical compounds, piperine and dihydroquercetin can improve your body’s utilization of vitamin C.5-7
Piperine, a unique alkaloid found in black pepper, has been shown to significantly speed up vitamin C’s absorption into the bloodstream.5
Piperine has also been shown to increase absorption of various nutrients such as curcumin by favorably altering the characteristics of the cells lining the digestive tract.8 Studies on animals and in the lab demonstrate that piperine, administered orally, boosts cellular levels of vitamin C, especially in animals undergoing excessive oxidative stress, such as those with cancer.9,10 Higher levels appear to be the result of faster absorption, the characteristic effect of piperine.
In a human clinical study, a piperine-containing oral vitamin C supplement was superior to another “enhanced” vitamin C formulation, speeding the time to peak plasma concentrations of the vitamin. This resulted in a slight but important increase in the total exposure of subjects’ bodies to vitamin C in the first 4 hours following ingestion. At 30, 60, and even at 90 minutes post-ingestion, subjects taking the piperine-enhanced formulation had significantly higher plasma vitamin C than did subjects taking the other formulation.5
By shortening the time from ingestion to peak levels, the body can reap the benefits of a given dose of vitamin C for a longer time. Given the importance of vitamin C in thousands of biochemical reactions, this apparently slight advantage may make a large difference in health outcomes.
Dihydroquercetin is a potent flavonoid molecule found in grape leaf extracts.11 It optimizes vitamin C through a mechanism of action entirely different from piperine. Like all antioxidants, vitamin C is “used up” in the process of scavenging toxic reactive oxygen and nitrogen species.12 In scientific terms, active vitamin C “reduces” oxidant molecules by donating electrons, thereby becoming oxidized (and hence, inactive) itself.
Dihydroquercetin has been shown to donate electrons back to these oxidized vitamin C molecules, essentially making them brand new and regenerating their ability to combat oxidant damage in cells and plasma.7 When tested against other protective nutrients, only dihydroquercetin was capable of providing this vitamin C-regenerative effect.7
The dual effects on vitamin C of piperine (speeding absorption) and dihydroquercetin (speeding renewal) add up to a novel formulation that reaches peak plasma levels faster to keep cellular levels optimized longer.5 This represents a new “harder working” form of vitamin C.
Let’s now examine the potential impact of such optimization by reviewing the latest on vitamin C’s expanding role in health promotion.
Oxidative damage plays a central role in development of heart disease and strokes, as oxidized low-density lipoproteins (LDL) accumulate and trigger inflammatory reactions within blood vessel walls.13 Oxidation impairs endothelial function, the measure of blood vessels’ ability to regulate blood flow and pressure, potentially starving vital tissues (such as hard-working heart muscle) of their essential blood supply.14 Aging and chronic diseases such as diabetes bring on even more oxidation and loss of normal blood vessel function.14,15
Epidemiological studies demonstrate that people with the highest blood levels and daily intakes of vitamin C are at as much as a 50% reduced risk of developing or dying from cardiovascular diseases.16-23 Men with the lowest blood levels of vitamin C have a 2.4-fold greater risk of having a stroke compared with those having the highest levels of vitamin C. That risk is enhanced in men who had additional risk factors such as being overweight or hypertensive.24 And the risk of having high blood pressure in the first place is 22% lower in people with the highest vitamin C intake, compared with those having the lowest.25
One study found that people who took more than 700 mg/day of supplemental vitamin C had a 25% lower chance of developing coronary heart disease, the precursor of a heart attack.26
Studies of vitamin C administration directly into veins or arteries in human volunteers and people with arterial disease reveal a powerful effect on endothelial function, demonstrating immediate and significant improvements in blood flow and blood pressure.27-30 And studies of oral vitamin C supplementation at doses of 1,000 mg/day provide evidence of reduced oxidative damage to LDL cholesterol in diabetics, a group at very high risk for cardiovascular complications.31 A study of older adults, published in late 2012, showed a substantial and significant improvement in endothelial function following an oral dose of vitamin C, 1,000 mg, coupled with vitamin E and alpha-lipoic acid, two other natural antioxidants.15 Since it is difficult to maintain all-day optimal vitamin C blood levels, boosting the body’s absorption of vitamin C and reducing its degradation, as seen with piperine and dihydroquercetin, has intriguing therapeutic potential.
Cancer results from the mutation of genes that regulate cellular proliferation. Some of this DNA gene damage is caused by excess oxidation. Some studies suggest that 1 in 12 cancers might be prevented by assuring higher levels of antioxidant intake.32
And indeed, some studies show that those with the highest overall antioxidant vitamin intake are protected against many forms of cancer.
The best evidence for supplementation as a cancer preventive is found in cancers of the digestive tract. Vitamin C can prevent stomach colonization with the bacterium H. pylori, a major cause of stomach and small intestinal cancers.33 It does so, in part, by blocking an oxidant-induced enzyme the organism needs in order to set up shop in the stomach lining.33
Studies of supplementation with vitamin C, in combination with other antioxidant vitamins and minerals, demonstrate prevention of recurrent intestinal polyps (adenomas), the precursors of serious colorectal cancers.34,35 Similar findings have now been reported for esophageal cancer as well.36
There’s now evidence for a vitamin C protective effect in epidemiological and lab studies of breast cancer.37-39 One study showed that women who supplemented with vitamin C for more than ten years had a 42% reduced risk of developing breast cancer.38 And higher vitamin C intake produced a 65% reduction in risk of cancer of the cervix.40 Even pancreatic cancer, one of the deadliest malignancies known, was shown to be 33% less likely in those with higher blood levels of vitamin C.32
Again, dose and bioavailability of the vitamin seem to be critical; studies of vitamin C at 500 mg/day and lower tend not to demonstrate a significant protective effect.41 Furthermore, continued supplementation is a necessity; in one large clinical trial, supplementation with antioxidant vitamins including C decreased total cancer incidence and death rates, but that benefit disappeared within 5 years of stopping supplementation.42
High dose intravenous vitamin C has convincingly been shown to reduce markers of inflammation in cancer patients; we know that inflammation is critical to sustaining cancer cell reproduction and tumor growth.43 If we are to realize these benefits, we need to find ways to get the most out of our oral dosing, a goal that may be obtained through strategies like combining vitamin C with dihydroquercetin and piperine.
One important note: While vitamin C has been shown to be a valuable adjunct to conventional cancer treatment, the antioxidant power of vitamin C is so strong that it may have the potential to interfere with certain types of chemo- and radiation therapy, both of which can rely on producing free radicals to kill malignant cells.44 Due to the sensitive nature of radio- and chemotherapy administration, those who are currently undergoing chemo- or radiation therapy for a known cancer should speak with their treating oncologist regarding the best regimen and dosing of vitamin C for their individual situation.
The epidemics of obesity and type II diabetes have so much in common that they can be referred to as a single entity, diabesity. Oxidative stress is one of the central features of diabesity, being imposed by both excessive fat stores and by chronically elevated (or even borderline) blood sugar levels.45 Once tissue damage caused by glucose (glycation reactions) has taken place, there’s yet more oxidative stress. Together these factors account for most of the complications of diabesity, including poor cardiovascular outcomes, kidney disease, and nerve damage.
There’s been keen interest in the use of antioxidant vitamins to prevent diabesity’s complications. Studies with high-dose intravenous vitamin C show an immediate and marked reduction in aortic stiffness and central blood pressure during periods of acutely elevated glucose in human volunteers.46 That’s further confirmation of the idea that reliable tissue delivery of vitamin C has protective effects.
Additional evidence for vitamin C’s benefits in diabesity comes from supplementation studies demonstrating a reduction in markers of oxidative stress in obese adults, accompanied by favorable elevations in adiponectin, a protective fat-derived signaling molecule.31,47,48 And vitamin C, 1,000 mg/day plus vitamin E, 800 IU/day, significantly reduced the after-meal memory impairment that’s so common in type II diabetes, indicating that oxidative stress is involved in producing that phenomenon.49
Of course, the central concern for those with diabesity is getting control of their blood sugar. Studies show that vitamin C improves insulin sensitivity as a result of its antioxidant effects.50 The combination of vitamin C with vitamin E produces a further improvement, increasing glucose utilization without creating oxidizing byproducts.48,50 A further benefit of the combination is a reduction in a host of adhesion molecules that increase likelihood of blocked arteries.48
Vitamin C has been the subject of endless controversy regarding its ability to prevent the common cold. Strong evidence now supports the observation that doses of about 1,000 mg/day, taken regularly, can shorten the duration of a cold.51,52
But the beneficial effects of vitamin C go much beyond the common cold. Immune system cells of almost every variety are able to concentrate vitamin C from the blood (so long as ample vitamin C is available).52,53 Cells in the immune system fight infections in part by destroying invading organisms with bursts of oxidative activity, but that puts adjacent healthy tissue at risk.54 Supplementation with bioavailable vitamin C protects normal host tissues, allowing the infecting organism to be destroyed without collateral damage.51,54
These immune-boosting functions have a clear effect on another major health concern, stomach infection with Helicobacter pylori, a major cause of gastritis and stomach cancer. Studies show that following eradication of the organism by antibiotics, sustained daily vitamin C supplements (500 to 1,000 mg/day) reduce the severity of stomach irritation and inflammation, and may help to prevent progression to stomach cancer.36,55-57
Lung tissue naturally bears the brunt of the continuous oxidant assault on the body. When oxidant damage triggers inflammation (and vice versa) in the lungs, a protective reflex called bronchospasm occurs, which we experience as asthma or chronic obstructive pulmonary disease (COPD).58
Studies show that vitamin C levels are lower in asthmatic patients, the result of excessive degradation of the vitamin as it battles oxidant damage.59 High intakes of vitamin C are associated with improved lung function and a delay in the deterioration that could lead to chronic obstructive pulmonary disease.60 Asthmatic patients challenged with drugs that can trigger bronchospasm respond less severely if they are pre-treated with antioxidant vitamins C and E.61 And vitamin C supplementation at 1,500 mg/day has been shown to attenuate the severity of exercise-induced asthma attacks in patients with known asthma.62
Bones require a strong matrix of collagen proteins in order to develop and maintain their structural integrity and proper mineralization.63 Vitamin C is essential for collagen production, and epidemiologic studies link poor vitamin C intake with bone loss.63,64 Animal studies reveal that vitamin C supplementation prevents post-menopausal bone loss by stimulating new bone formation.64
Human studies suggest that vitamin C reduces rates of bone resorption, the principle cause of osteoporosis.65 In older men and postmenopausal women, higher vitamin C intake is associated with lower long-term bone loss.63,66 This leads directly to a reduction in the risk of hip and other non-vertebral fractures in people with the highest vitamin C intake.67
Supplementation with 1,000 mg/day of vitamin C has now been convincingly demonstrated to prevent oxidant-induced bone loss in elderly people.66
Vitamin C is gaining ever-greater attention for its potential to reduce the impact of chronic, age-related diseases. Yet the modest doses found in conventional multi-vitamin formulas have not demonstrated protective effects.
Vitamin C’s levels in the blood are under tight control, making it difficult to achieve optimal levels, even with very large oral supplement doses. That tight control arises from three basic mechanisms: control of absorption, control of excretion, and control of vitamin C degradation in the tissues.
Enhancing some or all of these mechanisms may allow us to push vitamin C blood levels higher than previously thought attainable.
The nutrients piperine and dihydroquercetin, acting by different mechanisms, offer just such an opportunity: piperine for optimizing vitamin C uptake and dihydroquercetin for sustaining its activity.
And enhanced bioavailability is desirable, in light of vitamin C’s many known beneficial properties. Studies demonstrate that the proper dose of vitamin C supplementation can reduce cardiovascular risks, lower the threat of cancer, mitigate diabesity, boost immune function, improve lung function, and even prevent bone loss in osteoporosis. Imagine the added benefits that even a modest increase in the vitamin’s serum profile could provide.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- 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.
- Krajcovicová-Kudlácková M, Dusinská M, Valachovicová M, Blazícek P, Pauková V. Products of DNA, protein and lipid oxidative damage in relation to vitamin C plasma concentration. Physiol Res. 2006;55(2):227-31. Epub 2006 May 24.
- Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care. 2002 Mar-Apr;5(2):66-74.
- Li Y, Schellhorn HE. New developments and novel therapeutic perspectives for vitamin C. J Nutr. 2007 Oct;137(10):2171-84.
- Morales I, Feldman S, Krieger DR, Kalman D. A clinical evaluation comparing the relative bioavailability of three vitamin C supplements in healthy non-smoking males. ACN. Vol 2009.
- Srinivasan K. Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Crit Rev Food Sci Nutr. 2007;47(8):735-48.
- Bors W, Michel C, Schikora S. Interaction of flavonoids with ascorbate and determination of their univalent redox potentials: a pulse radiolysis study. Free Radic Biol Med. 1995 Jul;19(1):45-52.
- Han HK. The effects of black pepper on the intestinal absorption and hepatic metabolism of drugs. Expert Opin Drug Metab Toxicol. 2011 Jun;7(6):721-9. Epub 2011 Mar 24.
- Selvendiran K, Senthilnathan P, Magesh V, Sakthisekaran D. Modulatory effect of Piperine on mitochondrial antioxidant system in Benzo(a)pyrene-induced experimental lung carcinogenesis. Phytomedicine. 2004 Jan;11(1):85-9.
- Vijayakumar RS, Nalini N. Efficacy of piperine, an alkaloidal constituent from Piper nigrum on erythrocyte antioxidant status in high fat diet and antithyroid drug induced hyperlipidemic rats. Cell Biochem Funct. 2006 Nov-Dec;24(6):491-8.
- Weidmann AE. Dihydroquercetin: More than just an impurity? Eur J Pharmacol. 2012 Jun 5;684(1-3):19-26.
- Goldenberg H, Landertshamer H, Laggner H. Functions of vitamin C as a mediator of transmembrane electron transport in blood cells and related cell culture models. Antioxid Redox Signal. 2000 Summer;2(2):189-96.
- Riccioni G, Frigiola A, Pasquale S, Massimo de G, D’Orazio N. Vitamin C and E consumption and coronary heart disease in men. Front Biosci (Elite Ed). 2012;4:373-80.
- Haidara MA, Yassin HZ, Rateb M, Ammar H, Zorkani MA. Role of oxidative stress in development of cardiovascular complications in diabetes mellitus. Curr Vasc Pharmacol. 2006 Jul;4(3):215-27.
- Wray DW, Nishiyama SK, Harris RA, et al. Acute reversal of endothelial dysfunction in the elderly after antioxidant consumption. Hypertension. 2012 Apr;59(4):818-24.
- Khaw KT, Bingham S, Welch A, et al. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet. 2001 Mar 3;357(9257):657-63.
- Yokoyama T, Date C, Kokubo Y, Yoshiike N, Matsumura Y, Tanaka H. Serum vitamin C concentration was inversely associated with subsequent 20-year incidence of stroke in a Japanese rural community. The Shibata study. Stroke. 2000 Oct;31(10):2287-94.
- Brown DJ, Goodman J. A review of vitamins A, C, and E and their relationship to cardiovascular disease. Clin Excell Nurse Pract. 1998 Jan;2(1):10-22.
- 19.Myint PK, Luben RN, Welch AA, Bingham SA, Wareham NJ, Khaw KT. Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study. Am J Clin Nutr. 2008 Jan;87(1):64-9.
- Ye Z, Song H. Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. Eur J Cardiovasc Prev Rehabil. 2008 Feb;15(1):26-34.
- Myint PK, Luben RN, Wareham NJ, Bingham SA, Khaw KT. Combined effect of health behaviours and risk of first ever stroke in 20,040 men and women over 11 years’ follow-up in Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): prospective population study. BMJ. 2009;338:b349.
- Pfister R, Sharp SJ, Luben R, Wareham NJ, Khaw KT. Plasma vitamin C predicts incident heart failure in men and women in European Prospective Investigation into Cancer and Nutrition-Norfolk prospective study. Am Heart J. 2011 Aug;162(2):246-53.
- Yildiran H, Mercanligil SM, Besler HT, Tokgozoglu L, Kepez A. Serum antioxidant vitamin levels in patients with coronary heart disease. Int J Vitam Nutr Res. 2011 Jul;81(4):211-7.
- Kurl S, Tuomainen TP, Laukkanen JA, et al. Plasma vitamin C modifies the association between hypertension and risk of stroke. Stroke. 2002 Jun;33(6):1568-73.
- Myint PK, Luben RN, Wareham NJ, Khaw KT. Association between plasma vitamin C concentrations and blood pressure in the European prospective investigation into cancer-Norfolk population-based study. Hypertension. 2011 Sep;58(3):372-9.
- Knekt P, Ritz J, Pereira MA, et al. Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts. Am J Clin Nutr. 2004 Dec;80(6):1508-20.
- Bruno RM, Daghini E, Ghiadoni L, et al. Effect of acute administration of vitamin C on muscle sympathetic activity, cardiac sympathovagal balance, and baroreflex sensitivity in hypertensive patients. Am J Clin Nutr. 2012 Aug;96(2):302-8.
- de Sousa MG, Yugar-Toledo JC, Rubira M, et al. Ascorbic acid improves impaired venous and arterial endothelium-dependent dilation in smokers. Acta Pharmacol Sin. 2005 Apr;26(4):447-52.
- Munzel T. Endothelial dysfunction: pathophysiology, diagnosis and prognosis. Dtsch Med Wochenschr. 2008 Nov;133(47):2465-70.
- Pleiner J, Schaller G, Mittermayer F, et al. Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion. Atherosclerosis. 2008 Mar;197(1):383-91.
- Mazloom Z, Hejazi N, Dabbaghmanesh MH, Tabatabaei HR, Ahmadi A, Ansar H. 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.
- Banim PJ, Luben R, McTaggart A, et al. Dietary antioxidants and the aetiology of pancreatic cancer: a cohort study using data from food diaries and biomarkers. Gut. 2012 Jul 23.
- Pal J, Sanal MG, Gopal GJ. Vitamin-C as anti-Helicobacter pylori agent: More prophylactic than curative- Critical review. Indian J Pharmacol. 2011 Nov;43(6):624-7.
- Paganelli GM, Biasco G, Brandi G, et al. Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas. J Natl Cancer Inst. 1992 Jan 1;84(1):47-51.
- Bonelli L, Puntoni M, Gatteschi B, et al. Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial. J Gastroenterol. 2012 Oct 13.
- Ma JL, Zhang L, Brown LM, et al. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J Natl Cancer Inst. 2012 Mar 21;104(6):488-92.
- Singh B, Bhat HK. Superoxide dismutase 3 is induced by antioxidants, inhibits oxidative DNA damage and is associated with inhibition of estrogen-induced breast cancer. Carcinogenesis. 2012 Oct 24.
- Pan SY, Zhou J, Gibbons L, Morrison H, Wen SW. Antioxidants and breast cancer risk- a population-based case-control study in Canada. BMC Cancer. 2011;11:372.
- Greenlee H, Kwan ML, Kushi LH, et al. Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort. Cancer. 2012 Apr 15;118(8):2048-58.
- Kim J, Kim MK, Lee JK, et al. Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea. Nutr Cancer. 2010;62(2):181-9.
- Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2009 Jan 7;301(1):52-62.
- Hercberg S, Kesse-Guyot E, Druesne-Pecollo N, et al. Incidence of cancers, ischemic cardiovascular diseases and mortality during 5-year follow-up after stopping antioxidant vitamins and minerals supplements: a postintervention follow-up in the SU.VI.MAX Study. Int J Cancer. 2010 Oct 15;127(8):1875-81.
- Mikirova N, Casciari J, Rogers A, Taylor P. Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J Transl Med. 2012;10:189.
- Conklin KA. Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr Cancer. 2000;37(1):1-18.
- Fenercioglu AK, Saler T, Genc E, Sabuncu H, Altuntas Y. The effects of polyphenol-containing antioxidants on oxidative stress and lipid peroxidation in Type 2 diabetes mellitus without complications. J Endocrinol Invest. 2010 Feb;33(2):118-24.
- Mullan BA, Ennis CN, Fee HJ, Young IS, McCance DR. Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia. Am J Physiol Heart Circ Physiol. 2004 Sep;287(3):H1262-8.
- Vincent HK, Bourguignon CM, Vincent KR, Weltman AL, Bryant M, Taylor AG. Antioxidant supplementation lowers exercise-induced oxidative stress in young overweight adults. Obesity (Silver Spring). 2006 Dec;14(12):2224-35.
- Vincent HK, Bourguignon CM, Weltman AL, et al. Effects of antioxidant supplementation on insulin sensitivity, endothelial adhesion molecules, and oxidative stress in normal-weight and overweight young adults. Metabolism. 2009 Feb;58(2):254-62.
- Chui MH, Greenwood CE. Antioxidant vitamins reduce acute meal-induced memory deficits in adults with type 2 diabetes. Nutr Res. 2008 Jul;28(7):423-9.
- Rizzo MR, Abbatecola AM, Barbieri M, et al. Evidence for anti-inflammatory effects of combined administration of vitamin E and C in older persons with impaired fasting glucose: impact on insulin action. J Am Coll Nutr. 2008 Aug;27(4):505-11.
- 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.
- Strohle A, Hahn A. Vitamin C and immune function. Med Monatsschr Pharm. 2009 Feb;32(2):49-54; quiz 55-6.
- 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.
- Chatterjee M, Saluja R, Kumar V, et al. Ascorbate sustains neutrophil NOS expression, catalysis, and oxidative burst. Free Radic Biol Med. 2008 Oct 15;45(8):1084-93.
- Sasazuki S, Sasaki S, Tsubono Y, et al. The effect of 5-year vitamin C supplementation on serum pepsinogen level and Helicobacter pylori infection. Cancer Sci. 2003 Apr;94(4):378-82.
- Zullo A, Rinaldi V, Hassan C, et al. Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized study. Aliment Pharmacol Ther. 2000 Oct;14(10):1303-9.
- Correa P, Fontham ET, Bravo JC, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst. 2000 Dec 6;92(23):1881-8.
- Riccioni G, Barbara M, Bucciarelli T, di Ilio C, D’Orazio N. Antioxidant vitamin supplementation in asthma. Ann Clin Lab Sci. 2007 Winter;37(1):96-101.
- Ford ES, Mannino DM, Redd SC. Serum antioxidant concentrations among U.S. adults with self-reported asthma. J Asthma. 2004 Apr;41(2):179-87.
- McKeever TM, Scrivener S, Broadfield E, Jones Z, Britton J, Lewis SA. Prospective study of diet and decline in lung function in a general population. Am J Respir Crit Care Med. 2002 May 1;165(9):1299-303.
- Trenga CA, Koenig JQ, Williams PV. Dietary antioxidants and ozone-induced bronchial hyperresponsiveness in adults with asthma. Arch Environ Health. 2001 May-Jun;56(3):242-9.
- Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JM. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med. 2007 Aug;101(8):1770-8.
- Sahni S, Hannan MT, Gagnon D, et al. High vitamin C intake is associated with lower 4-year bone loss in elderly men. J Nutr. 2008 Oct;138(10):1931-8.
- Zhu LL, Cao J, Sun M, et al. Vitamin C prevents hypogonadal bone loss. PLoS One. 2012;7(10):e47058.
- Pasco JA, Henry MJ, Wilkinson LK, Nicholson GC, Schneider HG, Kotowicz MA. Antioxidant vitamin supplements and markers of bone turnover in a community sample of nonsmoking women. J Womens Health (Larchmt). 2006 Apr;15(3):295-300.
- 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.
- Sahni S, Hannan MT, Gagnon D, et al. Protective effect of total and supplemental vitamin C intake on the risk of hip fracture--a 17-year follow-up from the Framingham Osteoporosis Study. Osteoporos Int. 2009 Nov;20(11):1853-61.