High-Dose Vitamin C: Megadosing, Pauling, and the Upper Limit

Linus Pauling won two Nobel Prizes, and spent his later years arguing that most people should be taking vitamin C by the gram.

His own study reported terminal cancer patients on roughly 10g a day surviving more than four times as long as controls. Two randomised trials at the Mayo Clinic then tested the same dose and found nothing at all.

Both results were real. This guide explains why they disagreed, what happens inside the body at gram-level doses, and where the evidence-based ceiling actually sits.

Table of Contents

1. Where the Megadose Idea Came From
2. What Happened When the Claim Was Tested
3. The Discovery That Explained Both Results
4. What Happens at 1,000mg and Above
5. Where the 2,000mg Upper Limit Comes From
6. What Pauling Got Right
7. The Alternative to Escalating the Dose
8. Frequently Asked Questions
9. Conclusion
10. Research References

1. Where the Megadose Idea Came From

The megadose idea did not start with a supplement company. It started with a Scottish surgeon, Ewan Cameron, who thought vitamin C might slow cancer by strengthening the tissue barriers tumours break through, and with a chemist who had already won 2 Nobel Prizes and was willing to lend the hypothesis his reputation.

In 1976 they published results from 100 terminal cancer patients given roughly 10g of ascorbate a day and compared them with 1,000 matched controls. The treated patients recorded a mean survival above 210 days against 50 days in the control group, and the authors reported that about 10% of them lived more than 20 times longer than controls.

Those are extraordinary numbers, and they travelled fast. Pauling's earlier book on vitamin C and the common cold had already put gram-level dosing into ordinary medicine cabinets, and the cancer papers turned a popular idea into what looked like a medical one. The design carried a flaw that would matter later: the 1,000 controls were drawn from hospital records rather than randomly assigned, and were chosen after the fact.

2. What Happened When the Claim Was Tested

The Mayo Clinic ran the first proper test in 1979. 150 patients with advanced cancer were randomly assigned, double-blind, to 10g of vitamin C a day or a matched lactose placebo, with 60 on vitamin C and 63 on placebo evaluable at the end. There was no appreciable difference in symptoms, performance status, appetite or weight, median survival was about 7 weeks in both arms, and the survival curves essentially overlapped.

Pauling objected that the Mayo patients had already had chemotherapy, which he argued had compromised their immune systems and left them unable to respond. So Mayo built the next trial around his objection. In 1985 they randomised 100 patients with advanced colorectal cancer, none of whom had received any cytotoxic drugs, to the same 10g a day or placebo.

The answer came back the same. No advantage in the interval before disease progressed, none in survival, and among patients with measurable disease, no objective improvement in a single person. Two double-blind randomised trials, at the dose he named, in the population he specified, is about as direct a test as medicine offers.

3. The Discovery That Explained Both Results

Something in the story still did not fit. Cameron had watched real patients, and the Mayo teams had run clean trials, and both groups reported honestly. In 2004 a team at the National Institutes of Health found the difference, and it had nothing to do with immune systems.

Cameron's patients received much of their ascorbate intravenously before switching to oral doses. The Mayo trials used oral vitamin C only. Measuring 17 healthy volunteers and modelling doses from 1g to 100g, the NIH group showed that intravenous administration produces plasma concentrations up to about 70 times higher than the highest tolerated oral dose.

The reason is that oral vitamin C is controlled at three points: how much the gut absorbs, how much the tissues take up, and how quickly the kidney returns it to the blood or lets it go. Taken by mouth, peak plasma concentration stays below roughly 300 µM whatever the dose; given intravenously it can reach 20 mM. The two sets of results were never in conflict. They were measuring two different exposures, and only one of them is reachable by swallowing tablets.

4. What Happens at 1,000mg and Above

The oral ceiling is not a vague limit. It has been mapped in detail. A 1996 depletion–repletion study took 7 volunteers down to under 5mg of vitamin C a day, then gave escalating doses from 30mg up to 2,500mg. Bioavailability was complete at a single 200mg dose and declined from 500mg upward.

The NIH puts absorption at 70–90% for intakes of 30–180mg a day, falling below 50% above 1g a day. Past that point, most of the additional dose leaves in the urine rather than reaching your tissues.

• At a single 200mg dose, absorption is essentially complete
• Above 500mg in one dose, a growing share is absorbed and then excreted
• Above 1,000mg a day, less than half of what you swallow is absorbed at all
• At 1,000mg daily, the 1996 study found urinary oxalate and urate excretion elevated compared with lower doses

That last point is where megadosing stops being merely wasteful. Oxalate is a component of the commonest kind of kidney stone, and it is the mechanism behind the safety signal in the next section. The full picture of how absorption falls away is in our guide to why most of a vitamin C dose is wasted.

5. Where the 2,000mg Upper Limit Comes From

The tolerable upper intake level for adults is 2,000mg a day, and what it was based on is worth knowing. The Institute of Medicine set it in 2000 on the adverse effect of osmotic diarrhoea and gastrointestinal disturbance — unabsorbed vitamin C drawing water into the bowel. That makes it a tolerability ceiling rather than a toxicity one, which is a meaningfully weaker claim than most people assume.

The reassuring half of the picture is well supported. Vitamin C has low toxicity, and the commonest complaints at high intakes are diarrhoea, nausea and abdominal cramps rather than anything lasting. The less reassuring half concerns kidney stones. An 11-year study of 23,355 Swedish men found a relative risk of 1.95 for kidney stones among ascorbic acid supplement users (95% CI 1.35–2.81), with a dose–response of 1.66 for fewer than 7 roughly 1,000mg tablets a week and 2.23 for 7 or more. The finding is in men, and it has not been shown in women.

Caution here is worth distributing unevenly. Some groups have a good reason to stay well below the limit:

• People with a history of kidney stones — the Linus Pauling Institute suggests considering avoiding supplemental doses at or above 1g a day
• People with kidney disease, where excretion of the excess is impaired
• People with haemochromatosis or another iron-overload condition, since vitamin C increases iron absorption
• Anyone taking prescription medication, where a physician should confirm there is no interaction

If any of those apply to you, talk to a doctor before supplementing at gram level. The wider safety picture is covered in vitamin C side effects and the upper limit.

6. What Pauling Got Right

It would be tidy to end the story with Pauling wrong about everything, and he was not. He argued that official intake targets were set to prevent deficiency rather than to support health, and that argument outlived him. Plasma vitamin C reaches steady state at 60–80 µmol/L on intakes of 200–400mg a day, which is several times the 90mg recommended for adult men and a level many diets do not reach consistently.

He was also right about safety. Vitamin C at gram doses is remarkably well tolerated, which is not something you can say of most substances people take by the gram.

His most famous claim did not fail cleanly either. A 2013 Cochrane review found that regular supplementation of 0.2g a day or more shortened colds by 8% in adults and 14% in children across 31 comparisons covering 9,745 cold episodes, while therapeutic dosing started at the first sign of symptoms showed no consistent effect on duration or severity. The review noted one large adult trial reporting benefit at an 8g dose, and concluded that more therapeutic trials are needed to settle the question.

Taking it regularly appears to help a little. Taking a great deal of it once you are already ill does not. The practical version of that distinction is in our vitamin C dosage guide.

7. The Alternative to Escalating the Dose

If the constraint on oral vitamin C is that the gut stops cooperating above a certain point, then raising the number on the label is the wrong lever to pull. The more useful question is whether the same milligrams can be delivered differently.

That is what liposomal delivery attempts. The vitamin C is enclosed in a phospholipid shell taken up by routes less dependent on the saturable transporters in the gut wall. A 2025 scoping review of 10 trials found higher absorption with liposomal forms in 9 of them, with AUC values 1.3 to 7.2 times higher than non-liposomal vitamin C.

The honest framing matters more here than in most articles. That range describes blood exposure, not clinical outcome, and the same review noted the absence of health-outcome data. Better absorption is a reason to expect a given dose to go further. It is not a reason to expect a different result, and it is not a licence to megadose by another route — the 2,000mg upper limit applies to total intake whatever the format.

Bio Absorb Nutraceuticals makes its Liposomal Vitamin C in a GMP-certified Canadian facility, in two formats: a liquid that mixes with water or juice, and capsules that need no refrigeration and travel well. Both are verified corn-free, which is unusual in a category where most ascorbic acid is corn-derived, and both are non-GMO, gluten-free, nut-free, dairy-free and vegan, with every batch third-party tested. See current serving details for the liquid or the full product specification for the capsules. Background on the delivery system is in the complete guide to liposomal vitamin C.

Frequently Asked Questions

Is it safe to take 5,000mg of vitamin C a day?

That sits well above the 2,000mg tolerable upper intake level, which was set on gastrointestinal tolerance rather than organ damage, so the likeliest consequence is diarrhoea and cramping rather than lasting harm. It is also inefficient: absorption drops below 50% above 1g a day, so a large share is excreted. Men with a history of kidney stones should discuss doses at that level with a physician first.

Was Pauling's vitamin C cancer research disproved?

The oral version of it was. A 1985 Mayo Clinic trial randomised 100 patients with no prior chemotherapy to 10g daily and found no advantage in progression or survival, replicating an earlier trial in 150 patients. Later pharmacokinetic work suggested the original observations may have reflected intravenous dosing, which reaches concentrations oral dosing cannot.

Does liposomal vitamin C let me megadose safely?

That is not what the evidence supports. The 1.3–7.2× AUC range reported for liposomal forms describes how much of a given dose reaches the blood, not permission to raise the dose. The 2,000mg upper limit applies to total intake regardless of format.

Is rebound scurvy real if I stop taking high doses?

There is no good evidence of it in healthy people who stop an oral supplement. There is an active argument about a rebound effect in critically ill patients: a 2024 reanalysis of a trial in critically ill COVID-19 patients attributes excess deaths between days 5 and 7.5 to the abrupt end of a 4-day intravenous course. That is a contested reading, and a very different situation from finishing a bottle of capsules.

What is the highest dose that has been studied safely?

In cancer research, doses up to 1.5g per kilogram of body weight have been given intravenously under supervision, with screening to exclude people who have G6PD deficiency, kidney disease or a history of stones. That is a monitored clinical setting rather than something to reproduce at home, and oral dosing cannot reach those concentrations in any case. How the routes compare is covered in IV vitamin C versus oral and liposomal forms.

If megadosing does not work, is there any point taking more than the RDA?

Probably, though "more" here means a few hundred milligrams rather than several grams. Plasma levels plateau at 60–80 µmol/L on 200–400mg a day, so pushing far beyond that changes blood concentration much less than the number on the bottle suggests. Consistency at a moderate dose tends to matter more than occasional large ones.

Conclusion

Pauling was right that many people sit below optimal vitamin C status and right that the vitamin is unusually safe; where he was wrong was in believing that swallowing grams of it could reach the concentrations his hypothesis needed, when oral plasma levels stop near 300 µM regardless of dose. The useful move is not a bigger number but a better-absorbed one. See current pricing and serving details for Bio Absorb's Liposomal Vitamin C.

Research References

1. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proceedings of the National Academy of Sciences, Vol. 73, No. 10 (1976), pp. 3685–3689. The original Cameron and Pauling report of 100 terminal patients on roughly 10g daily against 1,000 non-randomised controls.
2. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer: a controlled trial. New England Journal of Medicine, Vol. 301, No. 13 (1979), pp. 687–690. Double-blind randomised trial in 150 patients finding no difference in symptoms, performance status or survival at 10g daily.
3. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy: a randomized double-blind comparison. New England Journal of Medicine, Vol. 312, No. 3 (1985), pp. 137–141. Second Mayo Clinic trial, in 100 chemotherapy-naive patients, again finding no benefit.
4. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proceedings of the National Academy of Sciences, Vol. 93, No. 8 (1996), pp. 3704–3709. Depletion–repletion study establishing complete bioavailability at a single 200mg dose, decline from 500mg, and elevated oxalate excretion at 1,000mg daily.
5. Vitamin C pharmacokinetics: implications for oral and intravenous use. Annals of Internal Medicine, Vol. 140, No. 7 (2004), pp. 533–537. Showed intravenous dosing reaches plasma concentrations approximately 70 times higher than the highest tolerated oral dose, resolving the discrepancy between the Cameron and Mayo results.
6. Ascorbic acid supplements and kidney stone incidence among men: a prospective study. JAMA Internal Medicine, Vol. 173, No. 5 (2013), pp. 386–388. Eleven-year follow-up of 23,355 men finding a relative risk of 1.95 with a dose–response trend.
7. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews, 2013, Issue 1, Art. No. CD000980. Regular supplementation shortened colds by 8% in adults and 14% in children across 31 comparisons covering 9,745 cold episodes; cold incidence was unaffected across 29 comparisons in 11,306 participants, and therapeutic dosing started at symptom onset showed no consistent effect on duration or severity.
8. Rebound effect explains the divergence in survival after 5 days in a controlled trial on vitamin C for COVID-19 patients. Frontiers in Medicine, Vol. 11 (2024), article 1391346. Contested reanalysis arguing that abrupt cessation of high-dose intravenous vitamin C depresses plasma levels below baseline in critically ill patients.
9. Do liposomal vitamin C formulations have improved bioavailability? A scoping review identifying future research directions. Basic & Clinical Pharmacology & Toxicology, Vol. 137 (2025), article e70067. Reports AUC improvements of 1.3–7.2× in 9 of 10 trials while noting the absence of clinical outcome data.
10. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Institute of Medicine, National Academies Press (2000). Source for the adult tolerable upper intake level of 2,000mg/day, set on osmotic diarrhoea and gastrointestinal disturbance.
11. High-Dose Vitamin C (PDQ®) — Health Professional Version. National Cancer Institute, National Institutes of Health. Source for the oral plasma ceiling below 300 µM, intravenous concentrations up to 20 mM, and the 1.5g/kg supervised dosing figure with its screening criteria.
12. Vitamin C — Fact Sheet for Health Professionals. National Institutes of Health, Office of Dietary Supplements (2025). Source for absorption of 70–90% at 30–180mg/day falling below 50% above 1g/day, and for the low-toxicity characterisation.
13. Vitamin C — Micronutrient Information Center. Linus Pauling Institute, Oregon State University. Source for plasma steady state of 60–80 µmol/L at 200–400mg/day and the kidney stone caution at intakes of 1g/day or above.

About the Author

David Kimbell is a health writer, digital entrepreneur and former aerospace engineer, based in Ottawa, Canada. He loves translating complex science into clear, actionable guidance for consumers seeking evidence-based solutions.

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Important Disclaimers

Medical Disclaimer: This article provides educational information only and is not intended as medical advice. Always consult with a qualified healthcare provider before starting any new supplement, especially if you have existing health conditions, take medications, or are pregnant or nursing.

FDA/Health Canada Statement: These statements have not been evaluated by the Food and Drug Administration or Health Canada. This product is not intended to diagnose, treat, cure, or prevent any disease.