Lactobacillus Sporogenes Ruscus Aculeatus Vitamina C

Lactobacillus Sporogenes Ruscus Aculeatus Vitamina C

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Hepatitis is a condition that causes inflammation of your liver. Currently, there are an estimated 6 million people living with hepatitis in the United States, and more than 50,000 people are diagnosed with this disease every year. There are three primary types of hepatitis, and while their symptoms can be similar, they vary largely in the ways they're transmitted. Learning more about each type of hepatitis can help you better understand the condition as a whole.

Hepatitis A is the most easily transmitted of the three viruses. It affects approximately 2,500 people every year in the United States. It typically spreads through feces-contaminated food or water and is found in the feces of people who have the virus. Hepatitis A causes a short-term, acute sickness that most people heal from without treatment. However, it can cause serious illness in some people. This virus is more common in places with underdeveloped sanitation systems.

While doctors can't treat hepatitis A with medication, people who get this virus can manage its symptoms with fluids, rest and good nutrition. There's also a safe and effective vaccine available to protect you against hepatitis A.

What Is Hepatitis B?

Hepatitis B can occur both acutely (meaning it develops quickly and lasts a short time) and chronically (meaning it develops slowly over time and worsens over months or years). According to the Centers for Disease Control and Prevention, up to 2 million people in the United States are chronically affected with hepatitis B. Hepatitis B can be transmitted through sexual activity and exposure to infected blood. It can also be passed from a parent to their newborn child during birth.

Hepatitis B usually causes short-term discomfort that many people recover from completely after about four to eight weeks. However, it can turn into a chronic condition that lasts for years; this is more likely in older adults. Doctors can treat severe chronic hepatitis B with antiviral medications. However, in most cases, treatments focus on proper hydration and nutrition. There's a safe vaccine available to protect you against hepatitis B, too.

What Is Hepatitis C?

Photo Courtesy: BSIP/Getty Images

Approximately 4 million people in the United States are affected with hepatitis C. This form of hepatitis causes a chronic illness in over 50% of people who get this type of the virus. It's the least transmissible of the three viruses and can spread through contact with infected blood.

Hepatitis C occurs more commonly in people who engage in intravenous drug use. If you received a blood transfusion before 1992, you should also get tested for hepatitis C if you haven't previously. Hepatitis C can spread through unprotected sexual intercourse, but this is a less common way to transmit it. While there's no vaccine for chronic hepatitis C, treatments that are available today offer a 95% cure rate.

Chronic hepatitis C can significantly affect how your liver works. It can cause cirrhosis, which means that your normal liver tissue is replaced with scar tissue. It can also cause liver cancer. However, there are medications that can help keep this disease in check. Making lifestyle changes, such as reducing or eliminating alcohol from your diet, can also decrease your chances of experiencing complications. In severe cases, hepatitis C may require a liver transplant.

The varying forms of viral hepatitis affect millions of people in the United States. Chronic hepatitis often has few symptoms in its early stages, so recognizing the associated dangers and getting tested if you've been exposed may save your life. Although there are five types of viral hepatitis, only A, B and C are the forms commonly found in the United States.

Resource Links:

"Hepatitis A, B, and C: Learn the Differences," Immunization Action Coalition

"What's the Difference Between Hepatitis A, B and C?," UNC Health Talk

"The ABCs of Hepatitis," Centers for Disease Control and Prevention

"What's the Difference: Hepatitis B vs Hepatitis C?," Hepatitis B Foundation

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Lactobacillus Sporogenes Ruscus Aculeatus Vitamina C

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Is Vitamin C Good For Ckd Patients

Is Vitamin C Good For Ckd Patients

• Review
• Open Access
• Published: 12 February 2020

Dosing vitamin C in critically ill patients with special attention to renal replacement therapy: a narrative review

Annals of Intensive Care volume 10, Article number:23 (2020) Cite this article

• 9518 Accesses

• 9 Citations

• Metrics details

Abstract

Rationale/methods

The primary aim of the present contribution is to find a literature-based agreement on dose adjustments of vitamin C in critically ill patients undergoing renal replacement therapy (RRT).

Available data/study results

Critical illness is frequently accompanied by severe vitamin C deficiency. High-dose supplementation beneficially affects clinical outcome in small cohorts of patients with sepsis, burn injury, and trauma. There are no specific data on clinical outcomes in patients receiving renal replacement therapy (RRT). Vitamin C plasma concentrations in patients on RRT are comparable to critically ill patients not receiving RRT. Vitamin C is cleared from the circulation during RRT at a rate dependent on the plasma concentration, dose and duration of RRT. Sieving coefficient is about 1. While the dose of RRT is lower than normal renal function, tubular reabsorption is absent. Sparse evidence suggests that vitamin C dosing during continuous RRT should not exceed the dose administered to critically ill patients not receiving continuous RRT. Low plasma concentrations are expected during prolonged RRT because of persistent extracorporeal removal, absent renal reabsorption and enhanced metabolic loss due to circuit-induced oxidative stress. A dosage of twice 1 g vitamin C daily may be necessary to achieve normal plasma concentrations during RRT, but more studies are needed. There is no available evidence that high doses of vitamin C administered over a short period can induce oxalate stones or has pro-oxidant effects.

Conclusions

Supplementing vitamin C 1 g twice daily to critically ill patients has a solid pathophysiological rationale and a good safety profile. Patients on RRT probably need similar doses as critically ill patients not receiving RRT. Intravenous vitamin C in a dose of 2 g/day may be necessary to achieve normal plasma concentrations during RRT. However, data on dose adjustment of vitamin C during intermittent or chronic RRT are sparse and require more thorough pharmacokinetic and dose–response studies.

Rationale for supplementing vitamin C in critically ill patients

Vitamin C has anti-oxidant, anti-inflammatory, and immune-enhancing capacities, and acts as a cofactor for the synthesis of collagen, cortisol, catecholamines, and vasopressin [1]. Plasma vitamin C concentrations frequently flirt with scurvy levels in septic, trauma, and burn patients, after major surgery, and in any condition characterized by overwhelming systemic oxidative and inflammatory stress [2]. Diminished intake, increased consumption, and reduced recycling all contribute to this vitamin C deficiency. In line with its biological modulator functions and continued depletion in severe disease, restoring normal circulating vitamin C levels is thought to improve hemodynamics [3], limit organ failure, and benefit survival of critically ill patients. Promising results have been reported in small cohorts of patients receiving a repletion dose of vitamin C in combination with vitamin E. High-dose intravenous (IV) vitamin C significantly reduced fluid requirements, weight gain, and wound edema and improved renal and pulmonary function in the acute phase after burn injury [4]. Vitamin C infusion, alone [5,6,7] or in combination with thiamine and hydrocortisone [8], reduced biomarkers of inflammation and endothelial injury and had a positive impact on shock reversal, recovery from organ failure, and survival in severe sepsis and septic shock in a landmark before after trial [8], but not in the most recent vitamins trial which randomized septic shock patients to the above-mentioned cocktail or to hydrocortisone alone [9]. Apart from the hydrocortisone in all control patients, the vitamins trial differs from the before–after trial by a later timing of vitamin C (median more than 24 h after admission), and by less comorbidity. The value of early high-dose IV vitamin C treatment in ischemia/reperfusion injury has been extensively documented in animal experiments [10], but requires confirmation in clinical trials. Altogether, evidence on vitamin C supplementation is still fragmentary or inconclusive and does not support a widespread use in critically ill patients [11, 12]. For instance, regarding the CITRUS-ALI study which is widely quoted and promoted as a negative study; in actuality it is a double-positive study [13]. Indeed, the authors have recalculated the Sequential Organ Failure Assessment (SOFA) score as several errors did occur like for instance imputing the SOFA score prior to death in those patients who died prior to 96 h [5]. This reanalysis demonstrates a significant difference in SOFA scores between the two groups at 96 h and this reanalysis should be published soon [13]. Nevertheless, adjuvant vitamin C therapy holds particular promise in sepsis because of its apparent involvement in sepsis-related pathophysiological processes and the remarkably positive results in small clinical studies. A large number of randomized controlled trials (RCTs) are currently recruiting patients with sepsis and septic shock [14] to assess the benefit of vitamin C alone or in combination with hydrocortisone and thiamine.

Considerations on dosing of vitamin C in critical illness

The recommended daily dietary intake of vitamin C in healthy individuals is approximately 100 mg and produces plasma vitamin C levels between 60 and 100 µmol/L [15]. Vitamin C dosing in critically ill patients, however, is still an issue under debate. Also, it is unclear whether the dosing strategy should attempt to achieve normal or supraphysiologic (up to 1000 µmol/L) plasma vitamin C levels.

Some items pertaining to vitamin C dosing are known. First, intravenous (IV) dosing is crucial. Enteral uptake is unpredictable and may be seriously limited because the enteral transporter is satiable [1] and gut function often is impaired during critical illness. Second, high vitamin C doses (2–3 g/day) must be administered to restore plasma concentrations to normal [16, 17] and sustained therapy is needed to prevent reoccurrence of hypovitaminosis [17]. Third, a very high dose (100–200 mg/kg/day) is required to obtain supranormal plasma concentrations [4, 17]. Studies which showed beneficial effects on biological and clinical outcome parameters used very high vitamin C doses (66 mg/kg/h or 1584 mg/kg/day) on the first day of admission in burn patients [4] and 3 g, 6 g or 200 mg/kg daily in septic or trauma patients [5,6,7,8].

a. Pharmacokinetics of vitamin C

Vitamin C pharmacokinetics are best described by a two-compartment model with body weight and creatinine clearance as independent covariates [17]. In normal kidneys, vitamin C is filtered in the glomerulus and (partly) reabsorbed in the proximal convoluted tubule and the descending loop of Henle (see Fig. 1). Like enteral absorption, tubular reabsorption is satiable which accounts for a higher loss when plasma concentrations are high. Although the kidneys excrete about half of the administered vitamin C dose, the dose–concentration relationship is linear, implying that an x-times higher dose results in x-times higher plasma concentration [17]. Plasma concentrations following IV administration are expected to be significantly higher in anuric patients. Nearly half of critically ill patients have or develop acute kidney injury (AKI), and more than 20% need renal replacement therapy (RRT) within the first week of intensive care stay [18].

Fig. 1

Removal of vitamin C

Full size image

b. Pharmacokinetics of vitamin C during RRT

As a small (176 Da) water-soluble molecule, vitamin C concentration in ultrafiltrate or dialysate is equal to plasma (sieving coefficient around 1) [18]. Vitamin C removal during RRT, therefore, depends on the dose and duration of RRT, and on plasma concentrations (see Fig. 1) [19, 20]. During RRT, clearance is less than by glomerular filtration because the dose of standard RRT is lower than normal renal function. However, as vitamin C is not reabsorbed during CRRT, losses persist even in case of overt deficiency due to absent reabsorption. Furthermore, the decline in vitamin C plasma concentration during RRT is higher than expected when based on loss by filtration or dialysis, probably because of consumption related to substantial oxidative stress induced by the extracorporeal circuit [21], which leads to insufficient recycling of the oxidized vitamin C.

c. Clinical studies on plasma concentrations and loss of vitamin C during RRT

We have summarized the data of the five studies on vitamin C during RRT in Table 1. Vitamin C plasma concentrations in patients on RRT were found to be lower than in healthy controls, but comparable to critically ill patients not receiving RRT (see Table 1). Story et al. reported a daily median loss of 93 (range: 0–372) mg vitamin C in patients on continuous veno-venous hemofiltration (CVVH) [22]. Plasma vitamin C levels were reduced by 50% during a single intermittent hemodialysis session [19, 20]. Morena et al. observed a mean loss of 66 (range 8–230) mg vitamin C per session (200 mg/week) of intermittent chronic hemodiafiltration [19]. Pronounced vitamin C deficiency was reported in 80% of patients receiving continuous RRT (CRRT) for a mean duration of 2 weeks despite a daily IV dose of 500–1.000 mg supplemented for 7 days prior to vitamin C sampling [22].

Table 1 Table describing the pertinent studies examining vitamin C dosing in RRT

Full size table

Supplementing vitamin C during RRT by giving 1 g twice daily

Optimal plasma concentrations of vitamin C in critically ill patients on RRT are not known. Furthermore, symptoms of deficiency are difficult to diagnose during critical illness and are probably different from classical scurvy. The dose for supplementation of vitamin C during RRT to prevent scurvy or scurvy-like plasma concentrations of vitamin C is much lower as compared to pharmacological dosing. Apparently, doses of 1000 mg were not enough to avoid low plasma concentrations during RRT in a retrospective study [22]. The plasma vitamin C concentrations of the above described patient on CVVH receiving twice 1 g daily were within the normal range [22], suggesting that a twice daily dose of 1 g vitamin C may be sufficient to maintain normal plasma concentrations during CVVH [23]. However, more pharmacokinetic data are needed for an evidence-based recommendation of vitamin C to prevent deficiency. Plasma vitamin C concentrations in a patient on CVVH receiving 2 g/day were also similar to patients not on CRRT. In this case, the estimated daily effluent loss was 830 mg/day or 41% of the administered dose, which tended to be less than by the native kidney [23].

d. Pharmacological dosing of vitamin C to manipulate severe oxidative stress during RRT

Dosages of vitamin C should be higher if the goal is to influence redox homeostasis and enzyme function in sepsis and other conditions as severe burns [24]. A recent small case series reported plasma concentrations in CRRT patients supplemented with 6-g vitamin C daily [24]. Trough and peak concentrations were intentionally high (263 and 461 μmol/L resp.), but comparable to patients not receiving CRRT. Estimated effluent losses were 1680 mg/day or 28% of the administered dose. Plasma concentrations in patients with chronic renal insufficiency on intermittent hemodialysis were even higher [24]. Thus, based on the sparse available evidences, vitamin C dosing during CRRT should not exceed the dose administered to critically ill patients not on CRRT. Obviously, more pharmacokinetic data and dose–response studies are needed to settle this issue and randomized controlled trials (RCTs) are needed to evaluate clinical effects in septic AKI needing RRT.

e. Should a patient on RRT receive IV supplementation if they are on full enteral nutrition?

The answer is yes. Patients on RRT have similar plasma concentrations to critically ill patients not on RRT [23]. Critically ill patients exhibit hypovitaminosis C and vitamin C deficiency despite recommended enteral and parenteral intakes along with nutrition [25, 26]. Based on the scarce clinical data, a twice 1 g dose of intravenous vitamin C is needed to maintain normal plasma concentrations in critically ill patients with or without RRT on full nutrition [23], whereas 1 g/day seems insufficient [21].

f. Vitamin C dosing during peritoneal dialysis (PD)

Vitamin C deficiency is common in patients undergoing maintenance hemodialysis (MHD) and continuous ambulatory peritoneal dialysis (CAPD). Vitamin C losses are lower in CAPD than in MHD [27]. Patients with chronic kidney disease (CKD) undergoing CAPD, however, are prone to increased oxidative stress (OS) which is associated with enhanced cardiovascular risk, peritoneal membrane changes, and ultrafiltration failure. Supplementation of vitamin C and E in CAPD patients significantly attenuated OS as reflected by an increase in erythrocyte antioxidant enzyme activity and total antioxidant capacity (TAC) and lower MDA and carbonyl compound concentrations [28].

g. Dosing considerations for patients with renal failure who are not on RRT

Removal of vitamin C by the kidney depends on plasma concentration. In case of hypovitaminosis tubular reabsorption is maximal and removal is minimal while losses are higher when plasma concentrations are high. In patients with severe AKI, plasma concentrations following IV administration are expected to be significantly higher, especially in anuric patients. Thus, dose reduction is needed in patients with renal failure who do not require RRT. Since no guidelines are found in the literature, dosing 1–2 g/day vitamin C dosing seems to be most appropriate to avoid overdosing in this population.

Renoprotective effects of vitamin C

In a recent animal study, 24 adult male Wistar rats were randomly distributed into three groups: Group I received sevoflurane only, whereas Groups II and III additionally received moderate (150 mg/kg) and high (300 mg/kg) doses of ascorbic acid. The study found a dose-dependent reduction of acute tubular necrosis in the ascorbic acid group [29]. In patients with severe sepsis and septic shock treated with colistin according to a modified pharmacokinetics–pharmacodynamics (PK/PD)-based dosing strategy, Dalfino et al. identified baseline renal impairment and older age as strong predictors of AKI occurrence. Concomitant administration of ascorbic acid markedly reduced AKI risk [30]. In the before–after study of Marik, less patients received RRT for AKI in the group receiving ascorbic acid (in combination with hydrocortisone and thiamine) [8].

Possible side-effects of treatment with vitamin C

Significant toxicity of high-dose vitamin C has not been reported in published clinical trials. However, in view of a potential increase in vitamin C supplementation in critical illness, vigilance remains imperative.

Some potential side-effects must be emphasized:

(A) Oxalate stones and nephropathy

High-dose vitamin C increases oxalate excretion [17] and may cause oxalate crystallization, stone formation and nephropathy in susceptible patients. Several cases have been reported in patients receiving vitamin C supplements [31, 32]. Gender is a risk factor for dose-dependent oxalate stone formation [32]. A vitamin C dose above 1000 mg/day was not associated with renal stone formation in women, yet 700 mg/day sufficed to induce stones in men [33]. Apart from primary hyperoxaluria, a rare inborn error of metabolism, risk factors include fat malabsorption due to small bowel resection, inflammatory bowel disease, chronic pancreatitis or gastric bypass (decreasing fecal oxalate excretion), underlying chronic kidney disease, urinary outflow obstruction [34]. However, in a recent prospective case series exploring high-dose vitamin C (up to 100 g IV thrice weekly), no renal stones or kidney injury were reported [35].

(B) Pro-oxidant effects

Theoretical concerns exist that high-dose vitamin C may exert pro-oxidant effects. By donating an electron during radical scavenging, vitamin C is converted to the ascorbate radical and after a further electron donation to dehydroascorbic acid (DHA). During this process, a more aggressive radical (i.e., superoxide) is converted to the less aggressive ascorbate radical which predominantly reacts with itself, thereby dismutating to DHA and ascorbate [1]. In addition, electrons from ascorbate can reduce copper and iron, and generate superoxide and hydrogen peroxide (H₂O₂). This pro-oxidant effect occurs when large doses are infused. Some cancers are susceptible to H₂O₂, while human cells are less so possibly because of the large reducing capacity of erythrocytes [1]. Significant toxicity of high-dose vitamin C has not been reported in published clinical trials. However, given that relatively few patients have been enrolled to date, additional side-effects cannot be excluded.

(C) Incorrect glucose readings

Amongst other factors, high concentration of ascorbic acid interfere with glucose readings from finger stick blood glucose (FSBG) meters [36]. A classic case of marked interference with FSBG readings is due to intravenous ascorbic acid, because the devices recognized ascorbic acid as glucose and erroneously detects hyperglycemia if ascorbic acid levels are high. Factitious hyperglycemia may expose the patient to unwarranted insulin dosing errors. Spectrophotometric methods can be used to avoid unnecessary insulin with the risk of hypoglycemia.

(D) Hemolysis in G6PD deficiency

Several cases of hemolysis induced by pharmacological doses of IV ascorbic acid (> 60 g) in patients with G6PD deficiency have been published [36]. However, as recently reported low–moderate dose IV vitamin C may be the treatment of choice for drug-induced hemolysis in patients with G6PD deficiency [36]. Extrapolated from in vitro data, a dose of up to 6 g/day is not contraindicated in patients with G6PD deficiency [37]. Higher doses should be avoided in these patients [38].

Safety

Important side-effects of vitamin C are not reported in any of the mentioned controlled trials, also not in the most recent VITAMIN randomized trial [9]. Furthermore, vitamin C has been evaluated for treating atrial fibrillation in RCTs after cardiac surgery [39]. Meta-analyses also evaluated adverse events. They concluded that vitamin C was safe [40], although meta-analyses upon vitamin C should be taken with caution as recently shown [41].

Conclusions and future directions

Vitamin C is closely involved in pathophysiological processes related to ischemia–reperfusion, immunomodulation, and inflammation. Critical illness leads to a rapid exhaustion of vitamin C stores. Adjuvant therapy with vitamin C has been shown to mitigate organ injury in burn, sepsis, and post-cardiac surgery patients. The optimal dosing strategy in critically ill patients is unknown and a most effective or specific pathology-related dosing schedule remains to be established. However, at least 2–3 g IV vitamin C must be supplemented daily during the acute phase to normalize plasma concentrations. Preliminary clinical experience suggests that high-dose vitamin C therapy (≥ 6 g daily) in the acute phase is associated with better outcome and no significant toxicity. The promising results of adjuvant high-dose vitamin C alone or in combination with thiamine and hydrocortisone are currently being evaluated in large RCTs.

Scarce available data remain inconclusive regarding dose adjustments during RRT. However, vitamin C dosing during CRRT should probably not exceed the dose administered to critically ill patients not on CRRT, though this hypothesis needs to be confirmed in RCTs. Low plasma concentration can be expected during RRT for a prolonged time period due to persistent extracorporeal removal and metabolic loss due to circuit-induced oxidative stress accentuating the need for further pharmacokinetic and dose–response studies in the setting of CRRT. However, a dosage of about 1 g twice daily may be needed to obtain normal plasma concentration during RRT.

Availability of data and materials

Not applicable.

Abbreviations

IV:

Intravenous

SOFA Score:

Sequential Organ Failure Assessment Score

RCTs:

Randomized controlled trials

RRT:

Renal replacement therapy

CRRT:

Continuous renal replacement therapy

CVVH:

Continuous veno-venous hemofiltration

OS:

Oxidative stress

DHA:

Dehydroascorbic acid

H₂O₂ :

Hydrogen peroxide

MHD:

Maintenance hemodialysis

CAPD:

Continuous ambulatory peritoneal dialysis

PD:

Peritoneal dialysis

TAC:

Total antioxidant capacity

CKD:

Chronic kidney disease

PK/PD:

Pharmacokinetic/pharmacodynamics

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Author information

Affiliations

1. ICU Dept, Centre Hospitalier Universitaire Brugmann/Brugmann University Hospîtal, Place Van Gehuchtenplein, 4, 1020, Brussels, Belgium

   Patrick M. Honore

2. Development, Ageing & Pathology Research Department, Vrije Universiteit Brussel, Brussels, Belgium

   Herbert D. Spapen

3. Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, 825 Fairfax Av, Suite 410, Norfolk, VA, 23507, USA

   Paul Marik

4. Dept. of Anesthesiology, Intensive Care Medicine, Emergency Medicine & Pain Medicine, Ziekenhuis Oost-Limburg Genk, Genk, Belgium

   Willem Boer

5. Department of Intensive Care Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

   Heleen Oudemans-van Straaten

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PMH, HDS, PM, WB, and HOVS designed the paper and participated in drafting and reviewing. All authors read and approved the final manuscript.

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Correspondence to Patrick M. Honore.

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Honore, P.M., Spapen, H.D., Marik, P. et al. Dosing vitamin C in critically ill patients with special attention to renal replacement therapy: a narrative review. Ann. Intensive Care 10, 23 (2020). https://doi.org/10.1186/s13613-020-0640-6

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• Received: 27 August 2019

• Accepted: 06 February 2020

• Published: 12 February 2020

• DOI : https://doi.org/10.1186/s13613-020-0640-6

Keywords

• Vitamin C
• Renal replacement therapy
• Sepsis
• Burns
• Trauma
• High-dose vitamin C
• Peritoneal dialysis
• Prevention of acute kidney injury

Is Vitamin C Good For Ckd Patients

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How Much Vitamin C Can I Take At Once

How Much Vitamin C Can I Take At Once

The Benefits of Vitamin B Supplements

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Vitamin B is a crucial resource in your body, yet many people don't consume enough vitamin B with diet alone. Vitamin B vitamins are necessary for both men and women, especially older adults and those with certain medical conditions. Because vitamin B comes in many forms, it can be confusing to figure out exactly how to take for the most health benefits.

Types of Vitamin B Supplements

Vitamin B complex is a supplement that contains a combination of essential B vitamins so you don't have to take multiple pills each day. Some of the most effective vitamin brands include other vitamins as well, such as biotin, zinc, vitamin C and vitamin E. If you only want to take certain B vitamins, look for individual B1, B2, B3, B5, B6 and B12 supplements. If you're pregnant or obese, you need more of these vitamins, but it's good to check with your doctor for specific requirements.

Kidney Health

B Complex is one of the best vitamins for kidney health because each vitamin it contains has an important job. Vitamins B6, B12 and folic acid help prevent anemia, and the other B vitamins, such as riboflavin, thiamine and niacin, turn the food you eat into energy. If you have kidney disease, your vitamin requirements are different than someone who doesn't have it. Vitamin B6 works to make protein and red blood cells, vitamin B12 makes red blood cells and folate maintains nerve cells and assists in making new cells.

Anxiety and Depression

Vitamin B complex vitamins help with depression and anxiety. It's believed that when you're not getting enough B vitamins in your diet, it causes an imbalance in the brain neurotransmitters that create a signal to your brain, leading to depression. Vitamins B3 and B6 added with some folic acid can help improve your mood and reduce anxiety. You can visit your local natural vitamin shop to see what they have, but if you have questions, you should speak to a physician first or do some research to make sure you're taking the right supplements.

Other Conditions

Trials using vitamins B2, B9 and B12 have shown to benefit conditions such as rheumatoid arthritis and osteoarthritis. The reason these B vitamins are the best vitamins for arthritis is because they help reduce inflammation and improve joint mobility. Vitamin B12 is one of the best vitamins for fibromyalgia because low levels of the vitamin in your body can increase symptoms, making your pain and discomfort worse and causing muscle weakness, pins and needles, and unexplained aches and pains. B vitamins are some of the best vitamins to help tinnitus, or ringing in the ear. Many patients who have chronic ringing in their ears are deficient in B12. B vitamins are also the best vitamins for older men and heart health.

What to Buy

What to buy depends on what your body needs. It's helpful to determine your vitamin requirements based on age and sex before increasing your vitamin intake with your diet. Take time to learn about the top 10 vitamin brands and search vitamin company ratings to find something that works best for you. Vitamin E is good as an antioxidant, which protects the cells, so it's another vitamin that is worth considering. Vitamin G is good for improving healing capabilities and reducing inflammation. Vitamin D3 is used for treating and preventing bone disorders by assisting the body in absorbing calcium.

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Harga Cebion Vitamin C

Harga Cebion Vitamin C

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Whether in the form of a fizzy drink or flavored lozenges, cold and flu preventative supplements almost always highlight vitamin C as one of their key ingredients. So, what's so magical about vitamin C? Also known as ascorbic acid, vitamin C is critical to living healthily. Since the human body cannot spontaneously generate this nutrient, vitamin C must instead be absorbed from outside sources, such as vitamin supplements or foods that are naturally rich in it.

Commonly found in cold and flu preventative supplements, vitamin C strengthens and speeds up immune system functionality. Though research does not indicate that vitamin C intake alone can prevent the onset of cold or flu, adequate daily intake may shorten the duration of an infection or lessen the severity of symptoms.

Photo Courtesy: Catherine Falls Commercial/Moment/Getty Images

Vitamin C is crucial for the maintenance of well being. For example, it plays a role in wound healing and helps maintain many essential body tissues. It also acts as a potent antioxidant and can repair damage from free radicals, which are linked to aging effects, and disease vulnerability. Additionally, vitamin C can also prevent anemia, since it helps the body increase absorption of dietary iron, another vital mineral that the body cannot spontaneously create.

Foods that contain high concentrations of vitamin C have been linked with a lower risk of cardiovascular disease, like heart attack and stroke. Vitamin C can also increase levels of nitric oxide, a compound that widens blood vessels and, in turn, lowers blood pressure. In addition, regular intake of vitamin C, along with other vitamins, has been linked to a decreased risk for developing age-related cataracts, a leading cause of visual impairment in the United States.

Common Sources of Vitamin C

Vitamin C can be easily obtained through the many different foods, including:

Photo Courtesy: Akaradech Pramoonsin/Moment/Getty Images

• Citrus fruits and juices (orange, grapefruit, lemon, lime and tangerine)
• Berries
• Melons
• Mangoes
• Kiwi
• Tomato
• Broccoli
• Red peppers
• Spinach
• Squash
• Potatoes

Cooking these foods may result in the loss of some of the vitamin content, so it is ideal to ingest them raw, either whole or juiced. Nowadays, there are also numerous packaged food products, like cereals, that have been enriched and fortified with vitamin C, so that the nutrient can be easily obtained.

Vitamin C may also be labeled as "L-ascorbic acid" in supplement form, and most over-the-counter multivitamins contain the recommended daily amount of the vitamin. While it is a good source when an individual is in need of a vitamin C boost, supplements are not meant to replace a diet rich in naturally derived vitamin C.

What Happens When You Have Too Much — or Too Little — Vitamin C?

Vitamin C is a water-soluble vitamin that can be easily flushed out of the body via urination when it is not needed. Therefore, if the main source of vitamin C is from naturally occurring foods, it is near-impossible for excess vitamin C to produce side effects. However, taking excessive concentrated vitamin C supplements may lead to diarrhea or stomach upset.

Photo Courtesy: Violeta Stoimenova/E+/Getty Images

Since vitamin C-rich foods are so readily available nowadays, symptoms of inadequate vitamin C intake are also rare in the United States. However, malnourished individuals can experience symptoms of vitamin C deficiency over time, including:

• Weakness
• Fatigue
• Anemia
• Easy bruising
• Joint pain
• Skin breakdown
• Weakened tooth enamel
• Gum inflammation

Severe vitamin C deficiency is referred to as scurvy. Scurvy can be easily treated with increased dietary or supplemental vitamin C. Since vitamin C is crucial in the detoxification of the body, a lack of vitamin C can compromise the immune system and make an individual more susceptible to diseases and infections. Individuals with insufficient vitamin C may find that it takes longer than usual to recover from a cold or a physical wound.

Daily Dosage Recommendations:

The daily dosage recommendation for vitamin C is different for everyone, depending on factors such as gender, age, lifestyle and current health condition. The recommended daily dosage for vitamin C is at least 75 mg daily for women and 90 mg for men. Since people who are pregnant, breast feeding, smoking or using oral contraceptives have a lower blood level of vitamin C than others, larger doses of vitamin C may be needed to achieve optimal results in these individuals. Those who have prior or current medical conditions may also require bigger or smaller dosage levels, as recommended by their healthcare providers.

Resource Links:

• "Vitamin C" via MedlinePlus
• "Vitamin C and Infections" via MDPI
• "Extra Dose of Vitamin C Based on a Daily Supplementation Shortens the Common Cold: A Meta-Analysis of 9 Randomized Controlled Trials" via Hindawi, BioMed Research International
• "Vitamin C" via National Institutes of Health
• "Scurvy" via U.S. Department of Health & Human Services, National Institutes of Health
• "Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies" via The American Journal of Clinical Nutrition
• "Dietary vitamin and carotenoid intake and risk of age-related cataract" via The American Journal of Clinical Nutrition
• "Cardiovascular System" via Department of Anatomy, Seoul National University College of Medicine (via Springer)

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Harga Cebion Vitamin C

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Food Sources High In Vitamin C

Food Sources High In Vitamin C

This is a fact sheet intended for health professionals. For a reader-friendly overview of Vitamin C, see our consumer fact sheet on Vitamin C.

For information on vitamin C and COVID-19, see Dietary Supplements in the Time of COVID-19.

Introduction

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement. Humans, unlike most animals, are unable to synthesize vitamin C endogenously, so it is an essential dietary component [1].

Vitamin C is required for the biosynthesis of collagen, L-carnitine, and certain neurotransmitters; vitamin C is also involved in protein metabolism [1,2]. Collagen is an essential component of connective tissue, which plays a vital role in wound healing. Vitamin C is also an important physiological antioxidant [3] and has been shown to regenerate other antioxidants within the body, including alpha-tocopherol (vitamin E) [4]. Ongoing research is examining whether vitamin C, by limiting the damaging effects of free radicals through its antioxidant activity, might help prevent or delay the development of certain cancers, cardiovascular disease, and other diseases in which oxidative stress plays a causal role. In addition to its biosynthetic and antioxidant functions, vitamin C plays an important role in immune function [4] and improves the absorption of nonheme iron [5], the form of iron present in plant-based foods. Insufficient vitamin C intake causes scurvy, which is characterized by fatigue or lassitude, widespread connective tissue weakness, and capillary fragility [1,2,4,6-9].

The intestinal absorption of vitamin C is regulated by at least one specific dose-dependent, active transporter [4]. Cells accumulate vitamin C via a second specific transport protein. In vitro studies have found that oxidized vitamin C, or dehydroascorbic acid, enters cells via some facilitated glucose transporters and is then reduced internally to ascorbic acid. The physiologic importance of dehydroascorbic acid uptake and its contribution to overall vitamin C economy is unknown.

Oral vitamin C produces tissue and plasma concentrations that the body tightly controls. Approximately 70%–90% of vitamin C is absorbed at moderate intakes of 30–180 mg/day. However, at doses above 1 g/day, absorption falls to less than 50% and absorbed, unmetabolized ascorbic acid is excreted in the urine [4]. Results from pharmacokinetic studies indicate that oral doses of 1.25 g/day ascorbic acid produce mean peak plasma vitamin C concentrations of 135 micromol/L, which are about two times higher than those produced by consuming 200–300 mg/day ascorbic acid from vitamin C-rich foods [10]. Pharmacokinetic modeling predicts that even doses as high as 3 g ascorbic acid taken every 4 hours would produce peak plasma concentrations of only 220 micromol/L [10].

The total body content of vitamin C ranges from 300 mg (at near scurvy) to about 2 g [4]. High levels of vitamin C (millimolar concentrations) are maintained in cells and tissues, and are highest in leukocytes (white blood cells), eyes, adrenal glands, pituitary gland, and brain. Relatively low levels of vitamin C (micromolar concentrations) are found in extracellular fluids, such as plasma, red blood cells, and saliva [4].

Recommended Intakes

Intake recommendations for vitamin C and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine (IOM) of the National Academies (formerly National Academy of Sciences) [8]. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender [8], include:

• Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
• Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.
• Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.
• Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.

Table 1 lists the current RDAs for vitamin C [8]. The RDAs for vitamin C are based on its known physiological and antioxidant functions in white blood cells and are much higher than the amount required for protection from deficiency [4,8,11]. For infants from birth to 12 months, the FNB established an AI for vitamin C that is equivalent to the mean intake of vitamin C in healthy, breastfed infants.

Table 1: Recommended Dietary Allowances (RDAs) for Vitamin C [8]

Age	Male	Female	Pregnancy	Lactation
0–6 months	40 mg*	40 mg*
7–12 months	50 mg*	50 mg*
1–3 years	15 mg	15 mg
4–8 years	25 mg	25 mg
9–13 years	45 mg	45 mg
14–18 years	75 mg	65 mg	80 mg	115 mg
19+ years	90 mg	75 mg	85 mg	120 mg
Smokers	Individuals who smoke require 35 mg/day more vitamin C than nonsmokers.

* Adequate Intake (AI)

Sources of Vitamin C

Food

Fruits and vegetables are the best sources of vitamin C (see Table 2) [12]. Citrus fruits, tomatoes and tomato juice, and potatoes are major contributors of vitamin C to the American diet [8]. Other good food sources include red and green peppers, kiwifruit, broccoli, strawberries, Brussels sprouts, and cantaloupe (see Table 2) [8,12]. Although vitamin C is not naturally present in grains, it is added to some fortified breakfast cereals. The vitamin C content of food may be reduced by prolonged storage and by cooking because ascorbic acid is water soluble and is destroyed by heat [6,8]. Steaming or microwaving may lessen cooking losses. Fortunately, many of the best food sources of vitamin C, such as fruits and vegetables, are usually consumed raw. Consuming five varied servings of fruits and vegetables a day can provide more than 200 mg of vitamin C.

Table 2: Vitamin C Content of Selected Foods [12]

Food	Milligrams (mg) per serving	Percent (%) DV*
Red pepper, sweet, raw, ½ cup	95	106
Orange juice, ¾ cup	93	103
Orange, 1 medium	70	78
Grapefruit juice, ¾ cup	70	78
Kiwifruit, 1 medium	64	71
Green pepper, sweet, raw, ½ cup	60	67
Broccoli, cooked, ½ cup	51	57
Strawberries, fresh, sliced, ½ cup	49	54
Brussels sprouts, cooked, ½ cup	48	53
Grapefruit, ½ medium	39	43
Broccoli, raw, ½ cup	39	43
Tomato juice, ¾ cup	33	37
Cantaloupe, ½ cup	29	32
Cabbage, cooked, ½ cup	28	31
Cauliflower, raw, ½ cup	26	29
Potato, baked, 1 medium	17	19
Tomato, raw, 1 medium	17	19
Spinach, cooked, ½ cup	9	10
Green peas, frozen, cooked, ½ cup	8	9

*DV = Daily Value. The U.S. Food and Drug Administration (FDA) developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for vitamin C is 90 mg for adults and children age 4 years and older [13]. FDA does not require food labels to list vitamin C content unless vitamin C has been added to the food. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

The U.S. Department of Agriculture's (USDA's) FoodData Central lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin C arranged by nutrient content and by food name.

Dietary supplements

Supplements typically contain vitamin C in the form of ascorbic acid, which has equivalent bioavailability to that of naturally occurring ascorbic acid in foods, such as orange juice and broccoli [14-16]. Other forms of vitamin C supplements include sodium ascorbate; calcium ascorbate; other mineral ascorbates; ascorbic acid with bioflavonoids; and combination products, such as Ester-C®, which contains calcium ascorbate, dehydroascorbate, calcium threonate, xylonate and lyxonate [17].

A few studies in humans have examined whether bioavailability differs among the various forms of vitamin C. In one study, Ester-C® and ascorbic acid produced the same vitamin C plasma concentrations, but Ester-C® produced significantly higher vitamin C concentrations in leukocytes 24 hours after ingestion [18]. Another study found no differences in plasma vitamin C levels or urinary excretion of vitamin C among three different vitamin C sources: ascorbic acid, Ester-C®, and ascorbic acid with bioflavonoids [17]. These findings, coupled with the relatively low cost of ascorbic acid, led the authors to conclude that simple ascorbic acid is the preferred source of supplemental vitamin C [17].

Vitamin C Intakes and Status

According to the 2001–2002 National Health and Nutrition Examination Survey (NHANES), mean intakes of vitamin C are 105.2 mg/day for adult males and 83.6 mg/day for adult females, meeting the currently established RDA for most nonsmoking adults [19]. Mean intakes for children and adolescents aged 1-18 years range from 75.6 mg/day to 100 mg/day, also meeting the RDA for these age groups [19]. Although the 2001–2002 NHANES analysis did not include data for breastfed infants and toddlers, breastmilk is considered an adequate source of vitamin C [8,14]. Use of vitamin C-containing supplements is also relatively common, adding to the total vitamin C intake from food and beverages. NHANES data from 1999–2000 indicate that approximately 35% of adults take multivitamin supplements (which typically contain vitamin C) and 12% take a separate vitamin C supplement [20]. According to 1999–2002 NHANES data, approximately 29% of children take some form of dietary supplement that contains vitamin C [21].

Vitamin C status is typically assessed by measuring plasma vitamin C levels [4,14]. Other measures, such as leukocyte vitamin C concentration, could be more accurate indicators of tissue vitamin C levels, but they are more difficult to assess and the results are not always reliable [4,9,14].

Vitamin C Deficiency

Acute vitamin C deficiency leads to scurvy [7,8,11]. The timeline for the development of scurvy varies, depending on vitamin C body stores, but signs can appear within 1 month of little or no vitamin C intake (below 10 mg/day) [6,7,22,23]. Initial symptoms can include fatigue (probably the result of impaired carnitine biosynthesis), malaise, and inflammation of the gums [4,11]. As vitamin C deficiency progresses, collagen synthesis becomes impaired and connective tissues become weakened, causing petechiae, ecchymoses, purpura, joint pain, poor wound healing, hyperkeratosis, and corkscrew hairs [1,2,4,6-8]. Additional signs of scurvy include depression as well as swollen, bleeding gums and loosening or loss of teeth due to tissue and capillary fragility [6,8,9]. Iron deficiency anemia can also occur due to increased bleeding and decreased nonheme iron absorption secondary to low vitamin C intake [6,11]. In children, bone disease can be present [6]. Left untreated, scurvy is fatal [6,9].

Until the end of the 18^th century, many sailors who ventured on long ocean voyages, with little or no vitamin C intake, contracted or died from scurvy. During the mid-1700s, Sir James Lind, a British Navy surgeon, conducted experiments and determined that eating citrus fruits or juices could cure scurvy, although scientists did not prove that ascorbic acid was the active component until 1932 [24-26].

Today, vitamin C deficiency and scurvy are rare in developed countries [8]. Overt deficiency symptoms occur only if vitamin C intake falls below approximately 10 mg/day for many weeks [5-8,22,23]. Vitamin C deficiency is uncommon in developed countries but can still occur in people with limited food variety.

Groups at Risk of Vitamin C Inadequacy

Vitamin C inadequacy can occur with intakes that fall below the RDA but are above the amount required to prevent overt deficiency (approximately 10 mg/day). The following groups are more likely than others to be at risk of obtaining insufficient amounts of vitamin C.

Smokers and passive "smokers"

Studies consistently show that smokers have lower plasma and leukocyte vitamin C levels than nonsmokers, due in part to increased oxidative stress [8]. For this reason, the IOM concluded that smokers need 35 mg more vitamin C per day than nonsmokers [8]. Exposure to secondhand smoke also decreases vitamin C levels. Although the IOM was unable to establish a specific vitamin C requirement for nonsmokers who are regularly exposed to secondhand smoke, these individuals should ensure that they meet the RDA for vitamin C [4,8].

Infants fed evaporated or boiled milk

Most infants in developed countries are fed breastmilk and/or infant formula, both of which supply adequate amounts of vitamin C [8,14]. For many reasons, feeding infants evaporated or boiled cow's milk is not recommended. This practice can cause vitamin C deficiency because cow's milk naturally has very little vitamin C and heat can destroy vitamin C [6,12].

Individuals with limited food variety

Although fruits and vegetables are the best sources of vitamin C, many other foods have small amounts of this nutrient. Thus, through a varied diet, most people should be able to meet the vitamin C RDA or at least obtain enough to prevent scurvy. People who have limited food variety—including some elderly, indigent individuals who prepare their own food; people who abuse alcohol or drugs; food faddists; people with mental illness; and, occasionally, children—might not obtain sufficient vitamin C [4,6-9,11].

People with malabsorption and certain chronic diseases

Some medical conditions can reduce the absorption of vitamin C and/or increase the amount needed by the body. People with severe intestinal malabsorption or cachexia and some cancer patients might be at increased risk of vitamin C inadequacy [27]. Low vitamin C concentrations can also occur in patients with end-stage renal disease on chronic hemodialysis [28].

Vitamin C and Health

Due to its function as an antioxidant and its role in immune function, vitamin C has been promoted as a means to help prevent and/or treat numerous health conditions. This section focuses on four diseases and disorders in which vitamin C might play a role: cancer (including prevention and treatment), cardiovascular disease, age-related macular degeneration (AMD) and cataracts, and the common cold.

Cancer prevention

Epidemiologic evidence suggests that higher consumption of fruits and vegetables is associated with lower risk of most types of cancer, perhaps, in part, due to their high vitamin C content [1,2]. Vitamin C can limit the formation of carcinogens, such as nitrosamines [2,29], in vivo; modulate immune response [2,4]; and, through its antioxidant function, possibly attenuate oxidative damage that can lead to cancer [1].

Most case-control studies have found an inverse association between dietary vitamin C intake and cancers of the lung, breast, colon or rectum, stomach, oral cavity, larynx or pharynx, and esophagus [2,4]. Plasma concentrations of vitamin C are also lower in people with cancer than controls [2].

However, evidence from prospective cohort studies is inconsistent, possibly due to varying intakes of vitamin C among studies. In a cohort of 82,234 women aged 33–60 years from the Nurses' Health Study, consumption of an average of 205 mg/day of vitamin C from food (highest quintile of intake) compared with an average of 70 mg/day (lowest quintile of intake) was associated with a 63% lower risk of breast cancer among premenopausal women with a family history of breast cancer [30]. Conversely, Kushi and colleagues did not observe a significantly lower risk of breast cancer among postmenopausal women consuming at least 198 mg/day (highest quintile of intake) of vitamin C from food compared with those consuming less than 87 mg/day (lowest quintile of intake) [31]. A review by Carr and Frei concluded that in the majority of prospective cohort studies not reporting a significantly lower cancer risk, most participants had relatively high vitamin C intakes, with intakes higher than 86 mg/day in the lowest quintiles [2]. Studies reporting significantly lower cancer risk found these associations in individuals with vitamin C intakes of at least 80–110 mg/day, a range associated with close to vitamin C tissue saturation [2,22,32].

Evidence from most randomized clinical trials suggests that vitamin C supplementation, usually in combination with other micronutrients, does not affect cancer risk. In the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study, a randomized, double-blind, placebo-controlled clinical trial,13,017 healthy French adults received antioxidant supplementation with 120 mg ascorbic acid, 30 mg vitamin E, 6 mg beta-carotene, 100 mcg selenium, and 20 mg zinc, or placebo [33]. After a median follow-up time of 7.5 years, antioxidant supplementation lowered total cancer incidence in men, but not in women. In addition, baseline antioxidant status was related to cancer risk in men, but not in women [34]. Supplements of 500 mg/day vitamin C plus 400 IU vitamin E every other day for a mean follow-up period of 8 years failed to reduce the risk of prostate or total cancer compared with placebo in middle-aged and older men participating in the Physicians' Health Study II [35]. Similar findings were reported in women participating in the Women's Antioxidant Cardiovascular Study [36]. Compared with placebo, supplementation with vitamin C (500 mg/day) for an average of 9.4 years had no significant effect on total cancer incidence or cancer mortality. In a large intervention trial conducted in Linxian, China, daily supplements of vitamin C (120 mg) plus molybdenum (30 mcg) for 5–6 years did not significantly affect the risk of developing esophageal or gastric cancer [37]. Moreover, during 10 years of follow-up, this supplementation regimen failed to significantly affect total morbidity or mortality from esophageal, gastric, or other cancers [38]. A 2008 review of vitamin C and other antioxidant supplements for the prevention of gastrointestinal cancers found no convincing evidence that vitamin C (or beta-carotene, vitamin A, or vitamin E) prevents gastrointestinal cancers [39]. A similar review by Coulter and colleagues found that vitamin C supplementation, in combination with vitamin E, had no significant effect on death risk due to cancer in healthy individuals [40].

At this time, the evidence is inconsistent on whether dietary vitamin C intake affects cancer risk. Results from most clinical trials suggest that modest vitamin C supplementation alone or with other nutrients offers no benefit in the prevention of cancer.

A substantial limitation in interpreting many of these studies is that investigators did not measure vitamin C concentrations before or after supplementation. Plasma and tissue concentrations of vitamin C are tightly controlled in humans. At daily intakes of 100 mg or higher, cells appear to be saturated and at intakes of at least 200 mg, plasma concentrations increase only marginally [2,10,22,31,37]. If subjects' vitamin C levels were already close to saturation at study entry, supplementation would be expected to have made little or no difference on measured outcomes [22,23,41,42].

Cancer treatment

During the 1970s, studies by Cameron, Campbell, and Pauling suggested that high-dose vitamin C has beneficial effects on quality of life and survival time in patients with terminal cancer [43,44]. However, some subsequent studies—including a randomized, double-blind, placebo-controlled clinical trial by Moertel and colleagues at the Mayo Clinic [45]—did not support these findings. In the Moertel study, patients with advanced colorectal cancer who received 10 g/day vitamin C fared no better than those receiving a placebo. The authors of a 2003 review assessing the effects of vitamin C in patients with advanced cancer concluded that vitamin C confers no significant mortality benefit [40].

Emerging research suggests that the route of vitamin C administration (intravenous vs. oral) could explain the conflicting findings [1,46,47]. Most intervention trials, including the one conducted by Moertel and colleagues, used only oral administration, whereas Cameron and colleagues used a combination of oral and intravenous (IV) administration. Oral administration of vitamin C, even of very large doses, can raise plasma vitamin C concentrations to a maximum of only 220 micromol/L, whereas IV administration can produce plasma concentrations as high as 26,000 micromol/L [47,48]. Concentrations of this magnitude are selectively cytotoxic to tumor cells in vitro [1,67]. Research in mice suggests that pharmacologic doses of IV vitamin C might show promise in treating otherwise difficult-to-treat tumors [49]. A high concentration of vitamin C may act as a pro-oxidant and generate hydrogen peroxide that has selective toxicity toward cancer cells [49-51]. Based on these findings and a few case reports of patients with advanced cancers who had remarkably long survival times following administration of high-dose IV vitamin C, some researchers support reassessment of the use of high-dose IV vitamin C as a drug to treat cancer [3,47,49,52].

As discussed below, it is uncertain whether supplemental vitamin C and other antioxidants might interact with chemotherapy and/or radiation [53]. Therefore, individuals undergoing these procedures should consult with their oncologist prior to taking vitamin C or other antioxidant supplements, especially in high doses [54].

Cardiovascular disease

Evidence from many epidemiological studies suggests that high intakes of fruits and vegetables are associated with a reduced risk of cardiovascular disease [1,55,56]. This association might be partly attributable to the antioxidant content of these foods because oxidative damage, including oxidative modification of low-density lipoproteins, is a major cause of cardiovascular disease [1,4,56]. In addition to its antioxidant properties, vitamin C has been shown to reduce monocyte adherence to the endothelium, improve endothelium-dependent nitric oxide production and vasodilation, and reduce vascular smooth-muscle-cell apoptosis, which prevents plaque instability in atherosclerosis [2,57].

Results from prospective studies examining associations between vitamin C intake and cardiovascular disease risk are conflicting [56]. In the Nurses' Health Study, a 16-year prospective study involving 85,118 female nurses, total intake of vitamin C from both dietary and supplemental sources was inversely associated with coronary heart disease risk [58]. However, intake of vitamin C from diet alone showed no significant associations, suggesting that vitamin C supplement users might be at lower risk of coronary heart disease. A much smaller study indicated that postmenopausal women with diabetes who took at least 300 mg/day vitamin C supplements had increased cardiovascular disease mortality [59].

A prospective study in 20,649 British adults found that those in the top quartile of baseline plasma vitamin C concentrations had a 42% lower risk of stroke than those in the bottom quartile [60]. In male physicians participating in the Physicians' Health Study, use of vitamin C supplements for a mean of 5.5 years was not associated with a significant decrease in total cardiovascular disease mortality or coronary heart disease mortality [61]. A pooled analysis of nine prospective studies that included 293,172 subjects free of coronary heart disease at baseline found that people who took ≥700 mg/day of supplemental vitamin C had a 25% lower risk of coronary heart disease incidence than those who took no supplemental vitamin C [62]. The authors of a 2008 meta-analysis of prospective cohort studies, including 14 studies reporting on vitamin C for a median follow-up of 10 years, concluded that dietary, but not supplemental, intake of vitamin C is inversely associated with coronary heart disease risk [55].

Results from most clinical intervention trials have failed to show a beneficial effect of vitamin C supplementation on the primary or secondary prevention of cardiovascular disease. In the Women's Antioxidant Cardiovascular Study, a secondary prevention trial involving 8,171 women aged 40 years or older with a history of cardiovascular disease, supplementation with 500 mg/day vitamin C for a mean of 9.4 years showed no overall effect on cardiovascular events [63]. Similarly, vitamin C supplementation (500 mg/day) for a mean follow-up of 8 years had no effect on major cardiovascular events in male physicians enrolled in the Physicians' Health Study II [64].

Other clinical trials have generally examined the effects on cardiovascular disease of supplements combining vitamin C with other antioxidants, such as vitamin E and beta-carotene, making it more difficult to isolate the potential contribution of vitamin C. The SU.VI.MAX study examined the effects of a combination of vitamin C (120 mg/day), vitamin E (30 mg/day), beta-carotene (6 mg/day), selenium (100 mcg/day), and zinc (20 mg/day) in 13,017 French adults from the general population [33]. After a median follow-up time of 7.5 years, the combined supplements had no effect on ischemic cardiovascular disease in either men or women. In the Women's Angiographic Vitamin and Estrogen (WAVE) study, involving 423 postmenopausal women with at least one coronary stenosis of 15%–75%, supplements of 500 mg vitamin C plus 400 IU vitamin E twice per day not only provided no cardiovascular benefit, but significantly increased all-cause mortality compared with placebo [65].

The authors of a 2006 meta-analysis of randomized controlled trials concluded that antioxidant supplements (vitamins C and E and beta-carotene or selenium) do not affect the progression of atherosclerosis [66]. Similarly, a systematic review of vitamin C's effects on the prevention and treatment of cardiovascular disease found that vitamin C did not have favorable effects on cardiovascular disease prevention [67]. Since then, researchers have published follow-up data from the Linxian trial, a population nutrition intervention trial conducted in China [38]. In this trial, daily vitamin C supplements (120 mg) plus molybdenum (30 mcg) for 5–6 years significantly reduced the risk of cerebrovascular deaths by 8% during 10 years of follow-up after the end of the active intervention.

Although the Linxian trial data suggest a possible benefit, overall, the findings from most intervention trials do not provide convincing evidence that vitamin C supplements provide protection against cardiovascular disease or reduce its morbidity or mortality. However, as discussed in the cancer prevention section, clinical trial data for vitamin C are limited by the fact that plasma and tissue concentrations of vitamin C are tightly controlled in humans. If subjects' vitamin C levels were already close to saturation at study entry, supplementation would be expected to have made little or no difference on measured outcomes [22,23,41,42].

Age-related macular degeneration (AMD) and cataracts

AMD and cataracts are two of the leading causes of vision loss in older individuals. Oxidative stress might contribute to the etiology of both conditions. Thus, researchers have hypothesized that vitamin C and other antioxidants play a role in the development and/or treatment of these diseases.

A population-based cohort study in the Netherlands found that adults aged 55 years or older who had high dietary intakes of vitamin C as well as beta-carotene, zinc, and vitamin E had a reduced risk of AMD [68]. However, most prospective studies do not support these findings [69]. The authors of a 2007 systematic review and meta-analysis of prospective cohort studies and randomized clinical trials concluded that the current evidence does not support a role for vitamin C and other antioxidants, including antioxidant supplements, in the primary prevention of early AMD [70].

Although research has not shown that antioxidants play a role in AMD development, some evidence suggests that they might help slow AMD progression [71]. The Age-Related Eye Disease Study (AREDS), a large, randomized, placebo-controlled clinical trial, evaluated the effect of high doses of selected antioxidants (500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene, 80 mg zinc, and 2 mg copper) on the development of advanced AMD in 3,597 older individuals with varying degrees of AMD [72]. After an average follow-up period of 6.3 years, participants at high risk of developing advanced AMD (i.e., those with intermediate AMD or those with advanced AMD in one eye) who received the antioxidant supplements had a 28% lower risk of progression to advanced AMD than participants who received a placebo. A follow-up AREDS2 study confirmed the value of this and similar supplement formulations in reducing the progression of AMD over a median follow-up period of 5 years [73].

High dietary intakes of vitamin C and higher plasma ascorbate concentrations have been associated with a lower risk of cataract formation in some studies [2,4]. In a 5-year prospective cohort study conducted in Japan, higher dietary vitamin C intake was associated with a reduced risk of developing cataracts in a cohort of more than 30,000 adults aged 45–64 years [74]. Results from two case-control studies indicate that vitamin C intakes greater than 300 mg/day reduce the risk of cataract formation by 70%–75% [2,4]. Use of vitamin C supplements, on the other hand, was associated with a 25% higher risk of age-related cataract extraction among a cohort of 24,593 Swedish women aged 49–83 years [75]. These findings applied to study participants who took relatively high-dose vitamin C supplements (approximately 1,000 mg/day) and not to those who took multivitamins containing substantially less vitamin C (approximately 60 mg/day).

Data from clinical trials are limited. In one study, Chinese adults who took daily supplements of 120 mg vitamin C plus 30 mcg molybdenum for 5 years did not have a significantly lower cataract risk [76]. However, adults aged 65–74 years who received 180 mg vitamin C plus 30 mcg molybdenum combined with other nutrients in a multivitamin/mineral supplement had a 43% significantly lower risk of developing nuclear cataracts than those who received a placebo [76]. In the AREDS study, older individuals who received supplements of 500 mg vitamin C, 400 IU vitamin E, and 15 mg beta-carotene for an average of 6.3 years did not have a significantly lower risk of developing cataracts or of cataract progression than those who received a placebo [77]. The AREDS2 study, which also tested formulations containing 500 mg vitamin C, confirmed these findings [78].

Overall, the currently available evidence does not indicate that vitamin C, taken alone or with other antioxidants, affects the risk of developing AMD, although some evidence indicates that the AREDS formulations might slow AMD progression in people at high risk of developing advanced AMD.

The common cold

In the 1970s Linus Pauling suggested that vitamin C could successfully treat and/or prevent the common cold [79]. Results of subsequent controlled studies have been inconsistent, resulting in confusion and controversy, although public interest in the subject remains high [80,81].

A 2007 Cochrane review examined placebo-controlled trials involving the use of at least 200 mg/day vitamin C taken either continuously as a prophylactic treatment or after the onset of cold symptoms [81]. Prophylactic use of vitamin C did not significantly reduce the risk of developing a cold in the general population. However, in trials involving marathon runners, skiers, and soldiers exposed to extreme physical exercise and/or cold environments, prophylactic use of vitamin C in doses ranging from 250 mg/day to 1 g/day reduced cold incidence by 50%. In the general population, use of prophylactic vitamin C modestly reduced cold duration by 8% in adults and 14% in children. When taken after the onset of cold symptoms, vitamin C did not affect cold duration or symptom severity.

Overall, the evidence to date suggests that regular intakes of vitamin C at doses of at least 200 mg/day do not reduce the incidence of the common cold in the general population, but such intakes might be helpful in people exposed to extreme physical exercise or cold environments and those with marginal vitamin C status, such as the elderly and chronic smokers [81-83]. The use of vitamin C supplements might shorten the duration of the common cold and ameliorate symptom severity in the general population [80,83], possibly due to the anti-histamine effect of high-dose vitamin C [84]. However, taking vitamin C after the onset of cold symptoms does not appear to be beneficial [81].

Health Risks from Excessive Vitamin C

Vitamin C has low toxicity and is not believed to cause serious adverse effects at high intakes [8]. The most common complaints are diarrhea, nausea, abdominal cramps, and other gastrointestinal disturbances due to the osmotic effect of unabsorbed vitamin C in the gastrointestinal tract [4,8].

In postmenopausal women with diabetes who participated in the Iowa Women's Health Study, supplemental (but not dietary) vitamin C intake (at least 300 mg/day) was significantly associated with an increased risk of cardiovascular disease mortality [59]. The mechanism for this effect, if real, is not clear and this finding is from a subgroup of patients in an epidemiological study. No such association has been observed in any other epidemiological study, so the significance of this finding is uncertain. High vitamin C intakes also have the potential to increase urinary oxalate and uric acid excretion, which could contribute to the formation of kidney stones, especially in individuals with renal disorders [8]. However, studies evaluating the effects on urinary oxalate excretion of vitamin C intakes ranging from 30 mg to 10 g/day have had conflicting results, so it is not clear whether vitamin C actually plays a role in the development of kidney stones [8,85-87]. The best evidence that vitamin C contributes to kidney stone formation is in patients with pre-existing hyperoxaluria [23].

Due to the enhancement of nonheme iron absorption by vitamin C, a theoretical concern is that high vitamin C intakes might cause excess iron absorption. In healthy individuals, this does not appear to be a concern [8]. However, in individuals with hereditary hemochromatosis, chronic consumption of high doses of vitamin C could exacerbate iron overload and result in tissue damage [4,8].

Under certain conditions, vitamin C can act as a pro-oxidant, potentially contributing to oxidative damage [8]. A few studies in vitro have suggested that by acting as a pro-oxidant, supplemental oral vitamin C could cause chromosomal and/or DNA damage and possibly contribute to the development of cancer [8,88,89]. However, other studies have not shown increased oxidative damage or increased cancer risk with high intakes of vitamin C [8,90].

Other reported effects of high intakes of vitamin C include reduced vitamin B12 and copper levels, accelerated metabolism or excretion of ascorbic acid, erosion of dental enamel, and allergic responses [8]. However, at least some of these conclusions were a consequence of assay artifact, and additional studies have not confirmed these observations [8].

The FNB has established ULs for vitamin C that apply to both food and supplement intakes (Table 3) [8]. Long-term intakes of vitamin C above the UL may increase the risk of adverse health effects. The ULs do not apply to individuals receiving vitamin C for medical treatment, but such individuals should be under the care of a physician [8].

Table 3: Tolerable Upper Intake Levels (ULs) for Vitamin C [8]

Age	Male	Female	Pregnancy	Lactation
0–12 months	Not possible to establish*	Not possible to establish*
1–3 years	400 mg	400 mg
4–8 years	650 mg	650 mg
9–13 years	1,200 mg	1,200 mg
14–18 years	1,800 mg	1,800 mg	1,800 mg	1,800 mg
19+ years	2,000 mg	2,000 mg	2,000 mg	2,000 mg

*Formula and food should be the only sources of vitamin C for infants.

Interactions with Medications

Vitamin C supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss their vitamin C intakes with their healthcare providers.

Chemotherapy and radiation

The safety and efficacy of the use of vitamin C and other antioxidants during cancer treatment is controversial [53,91,92]. Some data indicate that antioxidants might protect tumor cells from the action of radiation therapy and chemotherapeutic agents, such as cyclophosphamide, chlorambucil, carmustine, busulfan, thiotepa, and doxorubicin [54,91,93,94]. At least some of these data have been criticized because of poor study design [52]. Other data suggest that antioxidants might protect normal tissues from chemotherapy- and radiation-induced damage [91,93] and/or enhance the effectiveness of conventional cancer treatment [95]. However, due to the physiologically tight control of vitamin C, it is unclear whether oral vitamin C supplements could alter vitamin C concentrations enough to produce the suggested effects. Individuals undergoing chemotherapy or radiation should consult with their oncologist prior to taking vitamin C or other antioxidant supplements, especially in high doses [54].

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)

Vitamin C, in combination with other antioxidants, may attenuate the increase in high-density lipoprotein levels resulting from combination niacin–simvastatin (Zocor®) therapy [96,97]. It is not known whether this interaction occurs with other lipid-altering regimens [54]. Healthcare providers should monitor lipid levels in individuals taking both statins and antioxidant supplements [54].

Vitamin C and Healthful Diets

The federal government's 2020-2025 Dietary Guidelines for Americans notes that "Because foods provide an array of nutrients and other components that have benefits for health, nutritional needs should be met primarily through foods. ... In some cases, fortified foods and dietary supplements are useful when it is not possible otherwise to meet needs for one or more nutrients (e.g., during specific life stages such as pregnancy)."

For more information about building a healthy dietary pattern, refer to the Dietary Guidelines for Americans and the U.S. Department of Agriculture's MyPlate.

The Dietary Guidelines for Americans describes a healthy dietary pattern as one that:

• Includes a variety of vegetables; fruits; grains (at least half whole grains); fat-free and low-fat milk, yogurt, and cheese; and oils.

  Fruits, particularly citrus fruits, fruit juices, and many vegetables are excellent sources of vitamin C. Some ready-to-eat breakfast cereals are fortified with vitamin C.

• Includes a variety of protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products.
• Limits foods and beverages higher in added sugars, saturated fat, and sodium.


• Limits alcoholic beverages.


• Stays within your daily calorie needs.

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Disclaimer

This fact sheet by the Office of Dietary Supplements (ODS) provides information that should not take the place of medical advice. We encourage you to talk to your healthcare providers (doctor, registered dietitian, pharmacist, etc.) about your interest in, questions about, or use of dietary supplements and what may be best for your overall health. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice.

Food Sources High In Vitamin C

Source: https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/#:~:text=Citrus%20fruits%2C%20tomatoes%20and%20tomato,)%20%5B8%2C12%5D.

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