- Ascorbic Acid 25g in 50mL.
- Sodium Ascorbate equivalent Ascorbic Acid, 26.5g in 100mL
Immune support
Treatments are generally recommended 1 – 2 times per week but can be administered more frequently at the doctor's discretion and as indicated by patient needs.
1st treatment
- Generally, 15–25g Ascorbic Acid or 15–30g Sodium Ascorbate.
- Saline 0.9%, sterile water for injection, or glucose 5%: 250mL.
2nd and subsequent treatments
- 15–60g Sodium Ascorbate / 15–50g Ascorbic Acid.
- Saline 0.9%, sterile water for injection, or glucose 5%: 250mL.
Optional
- If previous symptomatic hypocalcaemia during infusion, consider 10mL Calcium Gluconate for a patient receiving 50g Ascorbic Acid or 60g Sodium Ascorbate or greater (1g/10mL), unless hypercalcaemic.
Support for people with cancer
- The usual treatment plan is two treatments per week for 6–8 weeks initially.
- If there is indication of benefit at review – including quality of life improvements, monitoring blood tests and any available scans - patient may continue with 1-2 treatments per week for another 6 weeks. If there is ongoing benefit, patient may continue treatment every 1 to 3 weeks longer-term. The administration of a standard EORTC QLQ-C30 questionnaire to monitor each patient's quality of life throughout treatment is recommended.
- If available, plasma vitamin C levels are tested once IVC dose is up to 1–1.1 g/kg of Ascorbic Acid or 1.1–1.2 g/kg of Sodium Ascorbate, until tolerance level is achieved. Plasma vitamin C levels are used to guide tolerance dosing. Aim for 350–400 mg/dL (Mikirova, et al., 2013; Chen, et al., 2015).
- Monitoring plasma vitamin C tests are conducted every 8–10 treatments to check tolerance levels are being maintained. Adjust IVC dose as required.
1st treatment
- Generally, 15–25g Ascorbic Acid or 15–30g Sodium Ascorbate.
- Saline 0.9% or sterile water for injection: 250mL.
2nd treatment
- 25–50g Ascorbic Acid or 30–60g Sodium Ascorbate.
- Saline 0.9% or sterile water for injection: 250 mL.
3rd and subsequent treatments
- Ascorbic Acid can be increased up to 1.1 g/kg for males, and 1 g/kg for females, as tolerated.
- Sodium Ascorbate can be increased up to 1.2 g/kg for males, and 1.1 g/kg for females, as tolerated.
- See the Preparing Intravenous Solutions section below for guidance on bag volumes.
Optional
- If previous symptomatic hypocalcaemia during infusion, consider 10mL Calcium Gluconate for a patient receiving 50g Ascorbic Acid or 60g Sodium Ascorbate or greater (1g/10mL), unless hypercalcaemic.
6.3.4. Consent for intravenous treatment
It is expected that each clinic will have its own approach to gaining the patient's written informed consent before beginning IVC treatment, reflecting its own professional obligations and advice. For your interest, this section presents one possible approach used at the Clinic.
How is consent understood?
An interactive process between health practitioner and patient
- Explain options.
- Expected risks, side effects, benefits and costs of proposed treatment.
- Convey information in form, language, manner suitable for patient.
- Requires:
- Trust.
- Non-pressured environment.
- Support people if wanted.
- Opportunity to ask questions/clarify/consider.
- Can take away information if want.
A patient right
Right to make an informed choice and to give informed consent.
“right to information that a reasonable consumer, in that consumer's circumstances, would expect to receive” (Information, choice of treatment and informed consent. Medical Council of NZ, March 2011).
Consent discussion – topics to cover
- Understanding IVC treatment for patient's condition.
- Discuss safety – any known concerns/issues.
- Discuss side effects.
- Discuss available evidence.
- Advise can withdraw consent at any time.
- Discuss cost.
- Check consent to communicate with other health providers.
- Advise that this treatment is not supported by the majority of doctors.
Additional resources:
6.3.5. Managing G6PD deficiency
Some people have a genetic deficiency which may cause haemolysis with high dose intravenous vitamin C (Campbell et al., 1975; Rees et al., 1993; Quinn et al., 2017; Lo & Mok, 2020; Juneja et al., 2022). Testing the patient’s G6PD level before giving any more than 30g of Sodium Ascorbate or 25g of Ascorbic Acid is strongly recommended.
- Testing for potential G6PD genetic deficiency.
- Managing the situation appropriately if the test result is below normal range.
Testing for G6PD Deficiency
(Clinical Experience; Labtests reference range)
- Testing for G6PD deficiency is required for all patients considering having more than 30g of Sodium Ascorbate or 25g of Ascorbic Acid intravenously.
- Administering up to 30g of Sodium Ascorbate or 25g of Ascorbic Acid intravenously is considered safe in patients with G6PD deficiency.
- Normal range for G6PD is > 6.9 U/g Hb.
If Results are Below 6.9 U/g Hb
(Clinical Experience; advice from Labtests pathologist)
- Repeat G6PD test.
- Notify the patient’s regular GP (if not yourself) that they have G6PD deficiency.
- Avoid administering > 30g of Sodium Ascorbate or 25g of Ascorbic Acid intravenously.
- Refer patients to www.patient.co.uk or a similar source for further information on G6PD deficiency.
- If you have any concern of low-grade haemolysis, order a haemolytic screen shortly after IVC administration: CBC, serum bilirubin, serum LDH, reticulocyte count.
Additional resources
6.3.6. Managing renal function
Poor initial or unnoticed subsequent deterioration in patient renal function may affect ability to handle intravenous vitamin C (IVC) treatment (McAllister et al., 1984; Wong et al., 1994; Alkhunaizi et al., 1996; Malhotra et al., 2020; Maike et al., 2022; Shen et al., 2023). It is advised that the renal function of patients is monitored throughout a course of treatment and that any changes are managed.
Renal Function Testing
(BPAC, 2022; Clinical Experience)
- Obtain a baseline renal function test (RFT) on all new patients.
- For those having IVC, repeat RFT at 4 weeks, 12 weeks and then every 12 weeks.
Managing Changes in Renal Function
- If the eGFR reduces 15-20%, repeat the RFT in 1-2 weeks. If there is further reduction, stop IVC and review patient as below.
- If the drop is within normal range (eGFR > 60) and is stable at recheck, review patient for obvious cause. If examination and investigation are normal, use clinical judgement to decide whether to either:
- continue IVC with precaution of frequent RFT checks, or
- stop IVC until cause is found.
Additional resources
6.3.7. Stand-down times
This section specifies desirable intervals between intravenous vitamin C (IVC) treatment and other forms of medical treatment or investigation.
IVC excretion
Vitamin C is promptly excreted by the kidneys with a half-life of around 2 hours (Stephenson et al., 2013; Nielsen et al., 2015). After an intravenous infusion blood levels of vitamin C return to normal after 8 - 10 hours.
Summary of stand-down periods
Because of potential interactions, a clear period is recommended between IVC and other treatments.
For example, if a patient is scheduled for Chemotherapy on a Wednesday, their previous IVC treatment is recommended to be no later than Monday.
Clear period after IVC, before procedure Procedure Clear period after Procedure, before IVC 24 hours Blood tests Nil 8–10 hours Capillary glucose Nil 24 hours MRI – with contrast 24 hours Nil MRI – no contrast Nil 24 hours CT scan – with contrast 24 hours Nil CT scan – no contrast Nil 24 hours PET scan 24 hours Nil X-Ray Nil Nil Ultrasound Nil 1 whole day Chemotherapy 2 days Ask Dr Daily oral chemotherapy Ask Dr 2 whole days Radiotherapy 5 days 24 hours Surgery Nil 24 hours Iron infusion 24 hours Blood tests
High dose IVC may sometimes cause artefactual lab test results by interference in assays: decreased readings of direct bilirubin, lipase, UIBC, total cholesterol, HDL/LDL cholesterol, triglycerides, and uric acid; increased readings of sodium, potassium, calcium, and creatinine (Meng et al., 2005; Martinello et al., 2006; Yesildal & Isman, 2020).
Blood glucose test strips will show false elevation of readings with raised serum Vitamin C because vitamin C can interfere with the chemical reaction on the glucose strip (Al-Obaidi et al., 2021).
Leave at least 24 hours between IVC infusions and blood tests including renal function or creatinine tests to avoid false readings.
Diabetics
For insulin-dependent patients who rely on test-strip readings for their insulin dose, there is a risk of overdose causing hypoglycaemia (Sartor et al., 2015; Zhang et al., 2020; He et al., 2021).
Diabetic patients should not rely on finger-prick (capillary) glucose tests until 8 - 10 hours after IVC treatment due to false elevation of readings when using test strips – possibly even 12 hours after treatment.
* NOTE: A laboratory serum glucose test is not affected (Jackson et al., 2006).
Scans and imaging
PET scan
Blood glucose levels have a significant influence on PET scans as increased glucose levels can decrease 18F-FDG uptake in the brain and in tumours because of direct competition between binding sites and enzymes, which may lead to a false negative scan (Bahr & Wilson, 2014; Surasi et al., 2014; Sarikaya et al., 2019).
As IVC will cause a falsely elevated reading on point-of-care glucometers therefore, it should be avoided for 24 hours prior to PET scan.
MRI/CT with contrast
Studies showed the contrast materials currently used – e.g. gadolinium for MRI, iodine-based compounds for CT – are generally safe in patients with normal kidney function whereas the incidence of contrast-induced nephropathy (CIN) is as low as 2% (Goldfarb et al., 2009). In these patients, the contrast medium injected is almost entirely passed out of the body within 24 hours.
One study has shown a protective effect on the kidneys of oral Vit C administered before and after contrast (Spargias et al., 2004) but conflicting results were reported in another study whereas combination of vitamin C and Pentoxifylline was administered to patients undergoing angioplasty (Shakeryan et al., 2013).
There were no reported nephropathy issues with IVC at the Clinic, and the Doctors’ consensus was that stand down should be 24 hours before and after CT or MRI with contrast, but oral vitamin C could be continued.
Surgery
Before surgery
Some researchers have shown positive effects of IV vitamin C administered just before and during surgery, such as less pain relief needed after surgery, less incidence of myocardial injury and less postoperative pulmonary complications after cardiac surgery, but only at lower doses, such as a few grams (Wang et al., 2014; Ayatollahi et al., 2017; Wang et al., 2020).
As IVC can affect blood test results, it is best to avoid IVC for 24 hours before surgery.
Anaesthesia
One study has shown reduced dosage of anaesthetics in patients undergoing total knee replacement surgery who received preoperative vitamin C infusion (Li et al., 2021). Animal studies suggest that vitamin C (given intramuscularly) before anaesthetic potentiates or enhances the effects of some anaesthetic agents (Elsa et al., 2005, Najafpour et al., 2007).
Recommendations regarding IVC and anaesthetic are the same as those for surgery.
After surgery
No stand down time is needed if the patient is able to attend.
Chemotherapy and radiotherapy
The results of recent clinical trials showed that combining IVC with chemotherapy and/or radiotherapy appeared to be safe, well tolerated and could effectively decrease standard therapy associated side effects (Bael et al., 2008; Monti et al., 2012; Welsh et al., 2013; Kawada et al., 2014; Ma et al., 2014; Hoffer et al., 2015; Schoenfeld et al., 2017; Zhao et al., 2018; Carr et al., 2018; Mansoor et al., 2021).
However, due to their small sample sizes and limited studies, it is recommended patients avoid IVC one day before and two days after chemotherapy; avoid IVC two days before and five days after radiotherapy.
If oral chemotherapy is given every day, normal stand-down times do not apply. Some of the clinical trials used IVC in conjunction with oral chemotherapy which seems to be safe, well tolerated and may synergistically increase survival time in some tumours (Bael et al., 2008; Schoenfeld et al., 2017; Allen et al., 2019). IVC may be given on a case by case basis after discussion with the patient.
Iron infusion
Ferinject or other iron infusion. Mean plasma clearance range from 2.6 – 4.4 mL/min and terminal half-life from 7 – 12 h (Medsafe Ferinject Datasheet, 2021).
There are theoretical concerns that some of the circulating iron may be chelated by the vitamin C or that vitamin C and high concentrations of infused iron may enhance free radical generation via the Fenton reaction, which results in tissue damage (Kontoghiorghes et al, 2020; Pal & Jana, 2020).
In the absence of published evidence of the safety of combining these treatments, it is advisable to leave 24 hours before and after iron infusion.
Additional resources:
6.3.8. Possible Effects of IVC – Patient Guidance
The following is material the Clinic provided to patients:
Common effects
During and after an infusion of vitamin C, you may experience some common effects. Most are mild and may last up to a few hours.
- Dehydration – You may feel thirsty during and after a vitamin C infusion. Please drink plenty of fluids, unless you are on a restricted fluids regime. If so, please discuss with our doctors.
- Reduced blood sugar – A vitamin C infusion can reduce your blood glucose level. Having a meal before your treatment and snacking during treatment reduces your risk of this. Please tell the nurses if you notice yourself sweating or feeling dizzy, shaky, or nauseous. We may need to give you a glucose drink to help you feel better.
- Cramps, headaches, tingling, numbness – You may experience cramps, headaches, tingling or numbness during the infusion. Tell a nurse if you feel shaky. We may need to give you a calcium and magnesium drink to help you with this.
- Irritation or pain – If you notice any irritation or pain during your infusion, please tell a nurse immediately. Sometimes if you move around, the needle gets dislodged and the infusion fluid will cause pain. Do your best to keep your arm still throughout the infusion. Occasionally people will notice increased pain at the site of a recent injury or trauma during an IVC infusion.
- Tiredness – You may feel tired after your treatment. Rest and drink plenty of fluids. This effect usually goes away after the first few infusions.
- Blood tests – A vitamin C infusion can make some blood test results artificially high (eg: creatinine level). Do your blood test before treatment or more than 24 hours after the infusion.
- Finger-prick glucose testing – For people with diabetes, do not rely on finger-prick (capillary) glucose test results for 8–10 hours after your treatment because a vitamin C infusion can make the results artificially high. A laboratory blood serum glucose test is not affected, however.
Uncommon effects
There are also several possible effects which are not common, and require medical attention:
- Redness, pain, or swelling – If you develop any redness, pain, or swelling after treatment please contact the Clinic staff urgently. If it is outside business hours, see a doctor at A&E or your GP's after-hours service.
- Sore kidneys or blood in urine – The Clinic monitors your kidney function while you have IVC treatment because there is a reported rare risk of increased kidney stones. The Clinic has not seen this in its patients. If you do notice pain in your kidney region (flanks) or any blood in your urine, please contact the Clinic staff.
- Darkened urine or jaundice – Some people have a genetic deficiency that means higher doses of vitamin C are inadvisable. The Clinic always test your G6PD enzyme level before giving more than 25g/30g of vitamin C. If you notice darkened urine or jaundice of your skin or eyes, please contact the Clinic urgently. If it is outside of business hours, see a doctor at A&E or your GP's after-hours service.
6.4. Delivering treatment
6.4.1. Equipment needed
Prepared IV bag with additives and primed IV giving set, tourniquet, selected butterfly or cannula needle, alcohol swabs, gauze square, prepared tape and/or opsite, felt tip pen.
6.4.2. Storing supplies
Store and dispose of injectables and other supplies as directed on their packaging and datasheets.
Ascorbic Acid or Sodium Ascorbate for injection should be kept refrigerated.
6.4.3. Preparing intravenous solutions
Each clinic has its own way of managing the preparation of IV bags. These are some helpful tips the Clinic picked up during its practice:
- Follow the specified storage temperatures and disposal periods for injectables to preserve their efficacy. After Sodium Ascorbate or ascorbic acid is mixed with water, it should be used within 6 hours or disposed of.
- Keep the preparation environment clean, and also use alcohol swabs for the injection ports on IV bags and the tops of any opened vials. Use aseptic technique throughout.
- Preparing bags requires focus so discourage others from interrupting.
Using Ascorbic Acid
The two forms of injectable vitamin C used are Ascorbic Acid or Sodium Ascorbate.
Ascorbic Acid Sodium Ascorbate Concentration 25g / 50mL 30g / 100mL Vial volume 50mL 100mL Carrier solutions
The carrier solution for administration can be 0.9% saline, sterile water for injection, or glucose 5%.
The dosage of Ascorbic Acid/Sodium Ascorbate may affect which carrier is prescribed. For more details, see the Injectable Preparations section above.
Bag volumes
The following are the Clinics recommendations for preparing solutions. Bag draining may be required.
Ascorbic Acid (50 mL vial) Ascorbic Acid dose Bag preparation < 50g Use a standard 250 mL bag of carrier solution. 50–100g Use a 500 mL bag of sterile water for injection. > 100g Drain 200 mL or more from a 1,000 mL bag of sterile water for injection. Sodium Ascorbate (100 mL vial) Sodium Ascorbate dose Bag preparation < 35g Use a standard 250 mL bag of carrier solution. 35–49g Drain 50 mL from a standard 250 mL bag. 50–90g Drain 100 mL from a 500 mL bag of sterile water for injection. > 90g Drain 200 mL or more from a 1000 mL bag of sterile water for injection. Calculate drip rate
Infusion rate for intravenous vitamin C must be no faster than 1 gram per minute.
- Volume = total volume of fluid in the IV bag, including all additives.
- Drip factor is stipulated on the IV giving set.
- It is recommended that the calculated drip rate is written on the bag directly.
Calculate: minimum* time (minutes) = IVC dose (grams),
(volume (mL) × drip factor (drops/mL)) ÷ time (minutes) = drips per minute
* Adjust upwards depending on the patient. Use a lower rate for first treatment/s and monitor tolerance.
6.4.4. Administering infusions
Pre-treatment patient check
As part of our standard clinical care, the Clinic's nurses administered a brief check before each treatment session. If there are any concerns about a patient's readiness for treatment, then an urgent doctor consultation is arranged. Questions, along the lines of the following can be asked:
- Q1 – How were you after your last IV treatment?
- Q2 – Since your last visit here, have you had any change in your condition or treatment schedule?
(prompt further if needed)…- seen a doctor or specialist,
- been to hospital,
- had or planning any scans or other treatment like chemo or radiotherapy,
- changed the medication or supplements you take,
- had any abnormal events (like vomiting or fever)?
Infusing
These are The Clinic's guidelines for administering an infusion:
- Check patient name, date of birth and vitamin C dose on IV bag with patient and against treatment sheet.
- Mark bag with start time, halfway, and expected finish time.
- Do not connect the IV if you feel there is a problem. If you are concerned about the patient showing unusual pallor, breathlessness, pulse, BP, or agitation, please alert doctor.
- Wash hands and insert cannula or 23-gauge butterfly needle, secure and connect IV.
- Set IV drip rate as calculated. Monitor every 5 minutes or so, as drip rate can alter very easily.
- Keep an eye on patient's IV site for any signs of tissuing (infiltration/extravasation). Instruct patient to inform nurse when they have pain at site or feel unwell in any way.
- Provide oral fluids (water, tea, juice) as required throughout the IV process, as IVC can cause mild dehydration and thirst. At doses above 30 grams observe for signs of hypoglycaemia.
- When an IV is removed, instruct patient to press firmly on the site for three minutes (or longer if the patient is taking anticoagulants since bleeding time will be prolonged).
6.4.5. Managing infusion problems
Emergencies
If a patient's condition requires urgent medical attention, follow your emergency procedures. Examples are: anaphylaxis, choking, collapse, hypocalcaemia, hypoglycaemia.
