MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Intravenous (IV) vitamin C seems to be recommended more and more, particularly by practitioners of so-called alternative medicine (SCAM). At least this is what this survey suggests:

We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA’s Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25g/50ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers’ yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue.

Yet, the potential harm associated with the use of IV vitamin C has not been systematically assessed. An international team of researchers aimed to fill this gap by reviewing the available evidence on harm related to such treatment. They included studies in adult populations that reported harm related to IV high-dose vitamin C which they defined as greater than or equal to 6 g/d, greater than or equal to 75 mg/kg/d, or greater than or equal to 3 g/m/d.

They identified 8,149 reports, of which 650 full text were assessed for eligibility, leaving 74 eligible studies. In these studies, 2,801 participants received high-dose vitamin C at a median (interquartile range) dose of 22.5 g/d (8.25-63.75 g/d), 455 mg/kg/d (260-925 mg/kg/d), or 70 g/m/d (50-90 g/m/d); and 932 or more adverse events were reported. Among nine double-blind randomized controlled trials (2,310 patients), adverse events were reported in three studies with an event rate per patient for high-dose vitamin C identical to placebo group in one study (0.1 [1/10] vs 0.1 [1/10]), numerically lower in one study (0.80 [672/839] vs 0.82 [709/869]), and numerically higher in one study (0.33 [24/73] vs 0.23 [17/74]). Six double-blind randomized controlled trials reported no adverse event in either group. Five cases of oxalate nephropathy, five cases of hypernatremia, three cases of hemolysis in glucose-6-phosphate dehydrogenase deficiency patients, two cases of glucometer error, and one case of kidney stones were also reported overall.

The authors concluded that there is no consistent evidence that IV high-dose vitamin C therapy is more harmful than placebo in double-blind randomized controlled trials. However, reports of oxalate nephropathy, hypernatremia, glucometer error, and hemolysis in glucose-6-phosphate dehydrogenase deficiency patients warrant specific monitoring.

So, is IV vitamin C safe or not?

I would interpret these findings as follows:

  • Clinical trials are often very poor yard-sticks for estimating safety; they are too small and often neglect to mention adverse effects.
  • When it come to evaluating the safety of therapeutic interventions, we must therefore often rely on case-reports, case series and other uncontrolled data.
  • Such data show that IV vitamin C has been associated with adverse effects, some of which are serious.
  • The incidence of such event remains unclear.

8 Responses to Intravenous high-dose vitamin C therapy: what are the dangers?

  • There are pharmacokinetic reasons for expecting harms and no benefits from high-dose vitamin C (https://pubmed.ncbi.nlm.nih.gov/11135611/). First, its absorption from the gut is saturable at low doses, so most of it is not absorbed after oral administration, leading to high concentrations in the gut. Even if it is given intravenously, its tissue uptake from the blood is also saturable, and therefore little of the dose enters the tissues. And thirdly, it is rapidly excreted by the kidneys and its reabsorption from the renal tubules is saturable, leading to high concentrations in the urine and a risk of renal damage.

    • thanks Jeffrey, most informative and concise.

      • Review some parenteral Vitamin C case studies from Klenner from 1936 through the 1970s. Magne or Dalton in the 1960s or Cathcart in the 1980s. Current medical establishment tries to reinvent the wheel, and clutches their pearls about potential toxicity and “high doses” which are a fraction of the doses used successfully in the past. I’ve been in medicine for 31 years, there is an increasing closed-mindedness and elitism, especially if clinical wisdom contradicts what is espoused in “accepted” textbook or journals.

  • Serious, but most conditions easily reversible with simple hydration, it seems. And it seems like the doctors doing the therapy werent paying attention.

    • “…it seems…”
      And your medical/biological qualifications Roger, that make you competent to form an opinion are…?

  • It appears (see below) that in some advanced cases, vitamin C can work too well, suddenly releasing an overwhelming toxic load from necrotic cancer cells, killing the patient – it must be introduced cautiously.

    From Here:
    https://ia803008.us.archive.org/18/items/Linus_Pauling_PDF/Cancer%20and%20vitamin%20C%20_%20a%20discussion%20of%20the%20-%20Cameron%2C%20Ewan%3BPauling%2C%20Linus%2C%201901-1994%2C%20j.pdf

    [Quote, page 164 – 165 (Chapter 21) of Cancer and Vitamin C by Pauling and Cameron]
    “Case Y (cancer of the testicle)
    Mr. Y was a 42-year-old railroad booking clerk, who had been previously investigated for infertility and azoospermia (absence of living sperm in his semen).

    He reappeared in August 1971 with rapidly developing painless enlargement of the left testicle. Orchidectomy (removal of the diseased testicle) was performed, and, as clinically expected, it proved to be malignant. Surgery was followed by a standard course of radiotherapy to the inguinal and paraaortic lymph nodes, but even before this course of treatment had been completed lung metastases had appeared on his chest x-ray photographs.

    He was readmitted to the hospital in December 1971, still reasonably fit, but with multiple lung metastases and in particular with a large fleshy metastasis growing from the upper gum. (This was in the days before cis-platinum, which now appears to offer significant help in such difficult situations.) He was commenced on intravenous ascorbate. 8 g per day, with disastrous results.

    Within 36 hours (at which time his ascorbate infusion was stopped) the metastasis within his mouth disintegrated, with hemorrhage that could barely be controlled. He became extremely confused, with high fever, and soon lapsed into unconsciousness, and in spite of all the usual resuscitative measures died some 15 days later. An autopsy was performed and the appearances were quite remarkable. He had innumerable metastases scattered throughout the brain, the lungs, and the abdomen, but the striking feature was that all these metastases were dead, and could easily be scooped out.”
    [end of quote]

    • It appears (see below) that in some advanced cases, BS can be dangerous.

    • That is a strange and sad story. I wold be interested to know what kind of testicular cancer this was. In a 42-year-old seminoma is by a long way the most common, and ought to be curable by the combination of surgery and radiotherapy (though these days we know that it is unnecessary to treat the inguinal nodes unless the scrotum has been breached by doing the wrong operation, and we also know that chemotherapy with carboplatin is equally effective and less toxic than radiotherapy).

      However, although these tumours mainly affect men in their 20’s, the rapid progression and the strange pattern of metastases (I have never seen testicular cancer spread to the gum) is more in keeping with NSGCT (non-seminomatous germ-cell tumour). They tend to spread in a more haphazard way than seminoma, including to the brain, which means that radiotherapy to the regional nodes is often not helpful in stage I disease, and current management is either combination chemotherapy (based on cisplatin) or else careful monitoring with a view to chemotherapy only if the disease relapses.

      With combination chemotherapy, metastatic NSGCT is considered to be curable in virtually every case, although the response to treatment is so rapid that if a metastasis has eroded into a major vessel, or (as occasionally happens) into the bowel, then it can leave behind a hole with consequent massive bleeding or perforation of the gut in a severely immunosuppressed patient, both of which are difficult situations to manage successfully. Of course this can happen without the tumour shrinking, and death resulting from a tumour eroding an artery is relatively common; sometimes this can be quite dramatic, for instance when a neck tumour invades the carotid. Another problem with bulky tumours responding well to treatment is tumour lysis syndrome, where dying tumour cells release their contents into the blood with serious metabolic consequences; happily we don’t see this very often due to prophylactic measures such as aggressive hydration and administration of allopurinol.

      It is interesting that he had a high fever. Many tumour cells are quite temperature-sensitive. William Coley, in the 1890’s, observed that cancers sometimes resolved dramatically following a serious infection, and he developed a mixture of bacteria, known as Coley’s Toxins, which he injected into cancer patients, sometimes with dramatic effect. However, the results were unpredictable and the treatment was quite dangerous. Other methods of inducing generalised or regional hyperthermia have been used since then in clinical trials, with varying success. Generalised hyperthermia is difficult to achieve and very unpleasant for the patient. Local hyperthermia is also problematic as the applied heat is usually conducted away from the area very quickly by the blood, meaning that this approach is only really suitable for superficial tumours, such as chest wall metastases from breast cancer. Various delivery systems have been tried, including microwaves, focused ultrasound (though more often this involves heating the affected structure to temperatures approaching 100 C, which ablates all tissue) and various implantable devices. So far all of these have remained experimental.

      [Trans-rectal focused ultrasound for prostate cancer is an exception – this was widely adopted by certain urologists as a treatment for prostate cancer after an aggressive marketing campaign by the manufacturers of the equipment in the absence of any trial data as to its efficacy, or even safety, and was a clear moneyspinner. After the cancers recurred, a number of these patients, many of them rendered impotent and incontinent by their treatment, came my way. Most of them would have been much better off having radiotherapy in the first place, or indeed nothing at all in some cases. This does show that experienced doctors aren’t immune to SCAM.]

      Coming back to your case history, I wonder whether the haemorrhage itself might also have played a role. Tumours have a very poor blood supply and most of the cells within them are ischaemic and non-viable. The profound hypotension lthat follows massive blood loss would have reduced their perfusion still further. Presumably he died as a result of multiple organ failure, either from ischaemia or sepsis, or probably both.

      It is a leap of faith in what appears to be an inadequately-documented case from 50 years ago to regard this as evidence in favour of high-dose intravenous vitamin C. When it comes to testicular NSGCT, nothing so far has proven to be any better than the combination of of the three chemotherapy drugs bleomycin, etoposide and cisplatin (known as BEP) which (with minor modifications) has been standard treatment since 1983 and is highly effective.

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