13 Megadosed Vitamin C Benefits: Overlooked Science, Supplements, Dosing & More

Large doses of supplementary vitamin C are one of the many forgotten health optimization biohacks.

Megadosed vitamin C acts like an amplifier:

• Neutralizing oxidative stress
• Regenerating other antioxidants
• Optimizing blood flow
• Normalizing metabolic lab values like cholesterol and triglycerides
• Supporting mitochondrial energy production

For decades, 2-time Nobel laureate Linus Pauling challenged conventional medicine by proposing that large doses of vitamin C could radically improve human health, lifespan, and performance.

Modern research is finally catching up, confirming many of his insights and exploring new frontiers like IV vitamin C for critical care, cancer support, and metabolic health.

In this post, you’ll learn the benefits of megadosed vitamin C, why and how megadosing works, what the science says, how to dose safely, and whether it’s worth it.

What Is Vitamin C?

Vitamin C, or ascorbic acid, is a water-soluble vitamin crucial for tissue repair, collagen formation, antioxidant protection, immune support, metabolic health.

Linus Pauling was one of the pioneering advocates of what modern medicine considers high-dose vitamin C.

Unlike most mammals, humans cannot synthesize or store vitamin C internally due to the evolutionary loss of the enzyme L-gulonolactone oxidase (GLO).

That’s why you must get your vitamin C through supplements or your diet.

Pauling’s work advanced the idea that exceeding conventional vitamin C recommendations, often above 6,000mg daily, confers overlooked health benefits. He considered vitamin C to be the foundational orthomolecular nutrient.

In his book How to Live Longer and Feel Better, Pauling cited countless case studies from other practitioners, researchers, and doctors:

• Albert Szent-Gyorgyi (who discovered vitamin C)
• Dr. Klenner
• Dr. Cameron
• Dr. Carl Pfieffer
• Irwin Stone

Despite strong advocacy by Pauling, much of the medical system met vitamin C megadosing with skepticism. Even today, standard daily intake recommendations are 75-90 mg, with cautions against higher doses.

Misinformation surrounding vitamin C stems from medical conservatism and confusion.

Pauling and colleagues argue that mainstream nutritional guidelines overlook the biochemical individuality of vitamin C needs and the evolutionary context of its function.

He also documents the systematic bias against natural therapeutics and the problems with the studies that “disprove” the value of higher dosed vitamin C. Not only that, but he shares his conversations with the researchers.

Despite this, both natural health advocates and researchers continue to explore this misunderstood substance.

What are the best whole food sources of vitamin C?

Whole food sources rich in ascorbic acid include many fruits and vegetables, especially Kakadu plums, acerola cherries, and camu camu berries.

Consume vitamin C-rich foods raw or minimally cooked to preserve maximal vitamin potency.

Below is a list of raw, whole foods highest in vitamin C content per 100 grams. These foods provide vitamin C in its natural and biologically active form, along with other synergistic nutrients.

Since you’re probably not eating hundreds of grams of these, many people turn to supplementation.

What are the forms of vitamin C supplements?

The main forms of vitamin C supplements include ascorbic acid, sodium ascorbate, calcium ascorbate, and liposomal vitamin C. Each has unique characteristics.

Only ascorbic acid exists naturally within food.

The other types, or chemical forms, are used in dietary supplements designed for improved absorption, reduced acidity, or enhanced delivery.

There’s no conclusive evidence that one form is systemically superior in absorption when taken orally (J Pharm Sci, Linus Pauling Inst).

Ascorbic acid remains the most studied and proven effective, especially for systemic health benefits.

Practitioners use buffered forms (sodium and calcium ascorbate) for their reduced acidity, or with patients who either have sensitive stomachs or require higher doses.

Vitamin C supplements also come in different delivery methods:

• Liquid
• Capsules
• Tablets
• Liposomal
• Gummies
• Powders
• Intravenous (IV)

Each form delivers bioavailable vitamin C but differs in gastrointestinal tolerance and absorption rates.

Of these forms, liposomal vitamin C is emerging from research as the most absorbable and efficient (J Lipos Res).

The liposomal form encapsulates ascorbic acid inside tiny lipid-based vesicles called liposomes.

Liposomes protect ascorbic acid from degradation by stomach acid and enhance its absorption into the bloodstream and cells (Nutr Metab Ins).

How Does Vitamin C Work in the Body?

Vitamin C works in the body primarily through its dual roles as a powerful antioxidant and a crucial enzyme cofactor.

Together, supporting many physiological processes essential for health and resilience.

Ascorbic acid as a powerful antioxidant

Vitamin C primarily, primarily as ascorbic acid, is a water-soluble molecule that acts as a potent reducing agent (ie it donates electrons) and neutralizes reactive oxygen species and free-radicals.

Normal metabolism results in increased levels of:

• Hydroxyl radicals
• Superoxide
• Hydrogen peroxide

Ascorbic acid’s ROS neutralization protects critical biomolecules (proteins, lipids, nucleic acids) from damage caused by this normal metabolism and environmental toxins.

This electron donation converts L-ascorbic acid to its oxidized form, dehydroascorbic acid (DHA), which is then recycled back to its reduced form inside cells. And it’s again ready to hunt down free radicals.

Pauling highlighted “redox” cycling as core to vitamin C’s biochemical functions (Am J Clin Nutr, J Am Coll Nutr).

Vitamin C notably helps recharge other antioxidants like alpha-tocopherol (vitamin E),

How vitamin C functions as a crucial cofactor

Vitamin C works as an enzymatic cofactor to synthesize collagen and carnitine, neurotransmitters, and regulation of iron metabolism.

It maintains metal ions like iron and copper in their active reduced forms within enzymes. For example, ascorbic acid keeps iron atoms in an active form inside enzymes.

These enzymes, in turn, help make collagen by adding special groups (hydroxyl groups) to the protein building blocks (amino acids) proline and lysine.

This process is important for keeping collagen strong, which supports the skin, blood vessels, and other tissues that hold the body together.

Ascorbic acid helps regulate cortisol levels and inflammation, contributing to healthy stress responses and immune system modulation.

Thus, vitamin C sustains structural integrity, cellular defense, energy production, and immune regulation through its antioxidant properties and enzyme cofactor actions.

What Are the Benefits of Megadosed Vitamin C?

Linus Pauling recommends megadosing vitamin C because modern diets lack sufficient supply and our lifestyles and environmental dramatically increase the body’s demand for beyond standard recommendations.

Megadosing compensates for amplified needs for vitamin C brought about by increased oxidative stress from:

• Pollution
• Psychosocial stress
• Toxins
• Infections
• Immune challenges

Furthermore, today’s diet provides lower levels of vitamin C due to pesticide use, poor soil quality, chemical additives, over processing, cooking, and bad food choices.

Couple this with the fact that your body can’t store or produce vitamin C (though you retain limited amounts in certain tissues for short-term needs).

Plus, vitamin C has a short half-life, depending on tissue saturation.

Linus Pauling asserts that daily intakes of 2 to 18 grams (or even higher) are necessary to rapidly:

• Boost antioxidant levels to more effectively reduce oxidative stress & reduce inflammation
• Optimize immune function to prevent & fight infections better
• Enhance metabolic functions to support longevity

This dosing range considerably exceeds the typical ‘Recommended Dietary Allowance’ (RDA) of 75–90 mg for adults.

Pauling’s recommended doses mimic those produced endogenously by other mammals. These are amounts unattainable through diet alone.

Let’s explore the benefits of megadosing vitamin C in a little more detail.

Strengthens the immune system

Famously, high-dose vitamin C bolsters immune defenses by enhancing both your body’s first line of defense (innate immune system) and memory-based defense system (adaptive immune system).

Ascorbic acid accumulates in white blood cells (up to 100X higher concentration than in plasma) and stimulates their activity.

That’s why, when sick, bowl tolerance often increases by 2-10X. When I get sick, I can easily take 20,000 mg without issue.

For example, megadose vitamin C increases neutrophils’ movement toward infection sites (chemotaxis), engulfing of microbes (phagocytosis), and microbial killing.

At the same time, it protects these cells from self-inflicted oxidative damage, improving resistance to infections and speeding recovery (Indian J Clin Biochem).

It supports the adaptive immune response by promoting lymphocyte development and antiviral cytokine production, such as interferon-A.

Linus’s analyses clearly indicated that most of the research showing no immune effect followed improper dosing protocols.

A clinical trial using hourly 1,000 mg doses of vitamin C (total 10,000 mg/day) found significantly reduced flu and cold symptoms compared to placebo (Molecules).

Similarly, a meta-analysis of 9 randomized trials concluded that extra vitamin C (above regular supplementation) shortened the duration of common colds and relieved symptoms like chest pain and fever (BMC Pub Health).

Reduces oxidative stress & inflammation

High-dose ascorbic acid dramatically lowers oxidative stress and inflammation, which are key drivers of aging and chronic diseases (Oxid Med Cell Longev).

Even in small amounts, vitamin C guards proteins, lipids, carbohydrates, and DNA from ROS.

At high concentrations it also helps “recycle” other antioxidants like vitamin E, glutathione, phenolics, and potentially vitamin A and CoQ10 back to their active forms. Further bolstering the body’s antioxidant capacity (LPI).

This effect is reflected in improved oxidative stress biomarkers.

For example, studies in patients under acute oxidative stress (such as severe infections or trauma) have reported lower levels of oxidative damage byproducts and improved organ function with intravenous vitamin C therapy (Molecules).

By mopping up excess ROS, a high dose of vitamin C mitigates inflammation, which translates to reduced tissue damage in conditions like sepsis or acute lung injury (JAMA).

Interestingly, at very high doses, vitamin C can exhibit a pro-oxidant effect in certain environments.

This pro-oxidant behavior is actually being studied for therapeutic effect (ie killing cancer cells), but it underscores that megadosing is not universally “antioxidant” in all contexts.

Lowers stress hormone cortisol & increases sex hormones like testosterone

Some research suggests that vitamin C positively impacts many key hormones, including cortisol, testosterone, thyroid, estrogen, and progesterone.

One 2024 study of 69 stressed patients found ascorbic acid supplementation improved levels of DHEA-S and cortisol by modulating the HPA axis and acting as a cofactor for the cortisol regulating enzyme 11B-hydroxylase (Stress Health).

Vitamin C supports the synthesis of steroid/sex hormones (testosterone and estrogen), protects hormone-producing cells against oxidative stress, improves blood flow (important for sexual function), and may slow the conversion of testosterone to estrogen (by inhibiting aromatase in certain circumstances).

This 2023 study found a positive correlation between ascorbic acid and higher testosterone levels in infertile males, suggesting a potential protective effect (Front Reprod Health).

A more recent 2025 study confirmed the hormone-protecting effects of vitamin C. In a rat model of lead toxicity, co-administration of vitamin C improved reproductive hormones testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and other parameters (Bioscience).

Yet another mouse study found that vitamin C deficiency also appears to worsen lipid metabolic profile, testosterone and estradiol levels, and IGF-1 regulation (J Nutr Metab).

A study of 31 humans with hypothyroidism found that vitamin C improves various biomarkers of thyroid health, including free T4, T3, and TSH (JCEM).

Another more recent 2024 study of 5,878 people found a strong correlation between vitamin C intake and thyroid function (Frontiers).

Promotes cardiovascular health

Higher vitamin C levels have been correlated with lower risk of coronary heart disease and stroke in large epidemiological studies (Am J Clin Nutr, Am Heart J).

Supplement trials, though, have been mixed on long-term outcomes (Eur J Cardiovasc Prev Rehabil). Likely due to uninformed dosing.

It may also limit oxidation of LDL cholesterol and slowing atherosclerotic plaque formation.

One meta-analysis of 13 randomized controlled trials found a −7.9 mg/dL reduction in LDL and a −20.1 mg/dL reduction in triglycerides (J Chiropr Med)

While high-dose vitamin C shows cardioprotective potential, its effects are moderate.

Also, some studies suggest vitamin C supplements benefit older or deficient individuals more than young, healthy people.

Enhances tissue repair & collagen production

Megadosed vitamin C supports rapid tissue repair by boosting collagen production (J Foot Ankle Surg). Collagen is the protein scaffold that holds skin, tendons, and blood vessels together.

Ascorbic acid acts as a cofactor for prolyl and lysyl hydroxylase enzymes, which stabilize collagen’s triple-helix structure (Genes Dis).

These enzymes need ascorbate to build strong, cross-linked collagen fibers that knit wounds and strengthen connective tissue.

When vitamin C levels drop, collagen synthesis falters. This leads to fragile tissue, poor wound closure, and bleeding gums, the hallmark signs of scurvy.

Supplying high-dose ascorbate reverses this by ensuring continuous enzymatic activity and optimal collagen cross-linking.

Clinical data reinforce this mechanism:

• After dental surgery, patients taking 1.5–2 g/day vitamin C healed faster and had fewer dry sockets than placebo groups (Antiox)
• In diabetics with foot ulcers, 500 mg twice daily for eight weeks led to full wound healing in all vitamin C-treated patients, compared to only ~55% of controls
• Among burn patients, IV high-dose vitamin C reduced edema and promoted new collagen deposition, speeding recovery (Crit Care)

These effects are most pronounced in vitamin C deficient individuals or those facing high oxidative stress.

In those already sufficient, megadoses don’t seem to significantly speed up healing.

UV protection & skin health

Vitamin C (or ascorbic acid) is commonly used in personal care products because it’s great for skin health and has properties that protect the body from damaging UV light.

One study titled, The Roles of Vitamin C in Skin Health, broke down exactly how this works (Nutrients):

• Antioxidant effects neutralize the ROS generated by UV light
• Enhanced collagen production maintains skin post exposure
• Protects against photoaging and damage
• Synergizes with other skin antioxidants like vitamin E

One of the great clues indicating its importance is that photodamaged skin has notably depleted vitamin C levels. This indicates that vitamin C gets actively consumed by the skin’s defensive processes.

Supports metabolism & energy

Megadosed vitamin C helps your body turn nutrients into energy more efficiently. It also supports brain chemicals that regulate alertness and work with B vitamins to fight fatigue (Front Med).

Vitamin C is a crucial cofactor in carnitine biosynthesis, the process that shuttles fatty acids into mitochondria for ATP (cellular energy) generation.

When vitamin C is low, this pathway falters, causing fatigue and reduced endurance (Nutr J, Nutr Metabol).

It also helps regenerate tetrahydrobiopterin (BH4), a coenzyme used for dopamine and norepinephrine synthesis. And these support focus and alertness (J Cardiovasc Pharmacol).

High-dose vitamin C enhances mitochondrial function and reduces oxidative stress, improving energy metabolism and recovery in stressed or ill individuals (Int J Mol Sci).

You can also check out other best mitochondrial supplements if you want to lean on that more.

Supports endothelial health

High-dose vitamin C benefits blood vessels through its antioxidant and enzymatic roles.

One key mechanism is improved ability of blood vessels to dilate and regulate blood flow (endothelial function).

Vitamin C protects the blood vessel lining (endothelium) by neutralizing oxidative radicals that otherwise degrade nitric oxide (a vasodilator).

By preserving nitric oxide and reducing oxidative damage to vessel walls, megadosed ascorbic acid helps arteries relax more effectively.

A 2014 meta-analysis of 44 clinical trials found that vitamin C supplementation (typically 500 mg – 2 g daily) significantly improved endothelial function in people with chronic conditions like atherosclerosis, heart failure, or diabetes (Atherosclerosis).

Notably, trials using >500 mg/day showed better vessel function, especially in older patients over 56 (Atherosclerosis).

Lowers blood pressure

Vitamin C megadosing modestly reduces blood pressure.

In a pooled analysis of 29 short-term trials (median dose ~500 mg/day), high-dose vitamin C lowered systolic blood pressure by about 3.8mmHg and diastolic by ~1.5mmHg on average (Am J Clin Nutr).

This antihypertensive effect is attributed to ascorbate’s ability to improve endothelial-dependent relaxation and act as a mild diuretic.

Reduces severity and mortality in COVID-19

Unsurprisingly, high-dose vitamin C consumption significantly lowers mortality risk and disease severity in COVID-19 patients through antioxidant and immunomodulatory actions (Front Med).

This is likely due to its strong antioxidative effects and vitamin C’s ability to help address the pro-inflammatory “cytokine storm.”

Case reports in COVID-19 patients noted improved oxygenation and lower inflammation markers after gram-dose vitamin C infusions (Rev Anti-Inf Thera).

If I had this illness, I’d certainly stack vitamin C with high-dose melatonin and methylene blue.

Potential anti-cancer effects

High-dose ascorbic acid induces oxidative stress selectively in cancer cells, promoting apoptosis and slowing tumor progression with minimal harm to normal cells (Genes Dis).

Aids in cancer therapy

Megadosed vitamin C has emerged as a potential supportive adjunct treatment for cancer.

This is backed by recent research that builds on Pauling’s initial theories.

At extremely high concentrations achievable by intravenous (IV) infusion (but too high for oral intake), ascorbic acid flips from antioxidant to pro-oxidant in the tumor microenvironment.

As a pro-oxidant, it generates hydrogen peroxide and ROS that selectively damage cancer cells while sparing normal cells (Genes Dis).

This effect exploits cancer cell vulnerabilities: Tumors often have lower antioxidant reserves and altered metabolism.

High-dose vitamin C does the following to cancer cells (Nat Rev Canc):

• Overloads their ROS defenses
• Inactivates glycolytic enzymes (like GAPDH) needed for tumor energy production (Science)
• Damages their DNA
• Depletes their ATP

Laboratory studies showed vitamin C selectively induces oxidative stress in KRAS or BRAF mutant colorectal cancer cells, impairing their growth (Science).

Clinically, there is growing evidence from small trials that IV vitamin C enhances chemotherapy and extends survival when added to standard cancer treatments.

A notable recent example is a 2024 randomized trial in patients with stage IV pancreatic cancer.

IV vitamin C (75 g, 3X/week) given alongside chemotherapy nearly doubled median overall survival (16 months vs 8.3 months on chemo alone).

They also had longer progression-free survival, without added toxicity (Redox Biol).

Other studies have reported that IV vitamin C can enhance the efficacy of chemotherapy and reduce chemo side effects such as fatigue.

Pauling’s legacy holds: NIH researchers confirmed IV delivery achieves 100X higher plasma levels than oral dosing, the threshold where vitamin C acts as an oxidative drug against tumors.

Some cancers, such as prostate cancer, show no measurable benefit, underscoring that results are tumor-specific and context-dependent. It should be viewed as a supportive therapy, not a cure.

Oncologists emphasize that while results are promising enough to warrant further trials, patients should not forgo proven treatments in favor of vitamin C megadose therapy.

Improves organ function & clinical outcomes in sepsis

IV megadose vitamin C helps reverse organ dysfunction in sepsis, especially lung and kidney impairment, while reducing the need for emergency blood-pressure–raising medications (vasopressors) to stabilize blood pressure (Brit J Pharmacol).

During sepsis, the body is flooded with free radicals and inflammatory cytokines that damage blood vessels and starve organs of oxygen.

High-dose ascorbic acid restores endothelial integrity, improves microcirculation, and supports mitochondrial energy production. Helping vital organs recover faster.

Clinical data show that when combined with thiamine and hydrocortisone, IV vitamin C can shorten ICU stays and lower mortality rates (Chest).

While researchers continue fine-tuning optimal dosing and timing, mounting evidence shows megadose vitamin C is a promising, low-risk way to support organ recovery in critically ill patients.

Accelerates recovery

Megadose ascorbic acid administered intravenously enhances recovery in critical care settings by reducing oxidative injury and supporting organ function (Brit J Pharmacol).

Studies show that high-dose IV vitamin C can:

• Shorten ICU stays (NEJM)
• Reduce vasopressor dependence
• Improve survival when combined with thiamine and hydrocortisone (JAMA)

The high plasma concentrations from Vitamin C IV infusion make ascorbic acid an even more potent antioxidant.

So that it neutralizes ROS that drives inflammation and tissue damage in sepsis and acute respiratory distress.

Is Megadosing Vitamin C Safe?

High-dose vitamin C is remarkably safe but has some contraindications.

Here’s what you should know before supplementing.

What’s the upper limit for ascorbic acid daily doses?

The US Institute of Medicine Panel on Dietary Antioxidants set 2,000 mg/day of vitamin C as the Tolerable Upper Intake Level (UL) for adults (Inst Med).

However, Pauling’s upper limit recommendation is much higher, as much as 12,000-16,000 mg/day. He reasons that,

“Our vitamin C consumption should be on par with what other animals produce by themselves, typically 10,000 mg – 12,000 mg a day.”

Pauling practiced what he preached and took 18,000 mg of ascorbic acid daily until he passed away in 1994.

He believed,

“…for different human beings the optimum intake lies between 250 mg/day and a much higher value, 5000 mg/day or more (Proc Natl Acad Sci).”

Indicating that optimal vitamin C intake varies depending on each individual’s biochemical and physiological status.

Linus Pauling suggested in the early 1970s that about 2,000 milligrams of vitamin C may be the optimum daily intake for most poeple, and that everyone should at least get 200-250mg/day (LPI).

Nick personally takes 3g of ascorbic acid, 2X daily.

What are the side effects of high-dose ascorbic acid?

Common adverse effects of vitamin C usually involve gastrointestinal discomfort.

These include:

• Diarrhea
• Nausea
• Stomach cramps
• Bloating
• Heartburn

Some have reported headaches, flushing, and dizziness.

In very rare cases, kidney stones can develop. Primarily among those predisposed or on prolonged extremely high doses with other risk factors.

Some folks believe that megadosing acidifies the urine, causing uric acid and oxalate levels to increase.

Does vitamin C interact with medications?

Vitamin C can interact with certain medications and therapies like phosphate binders, hormone therapy, and statins.

Ascorbic acid can increase aluminum absorption from phosphate binders, potentially harmful for kidney conditions.

It can raise estrogen levels when combined with birth control or hormone therapy.

It also influences the absorption or efficacy of:

• Protease inhibitors
• Statins
• Niacin
• Iron
• Warfarin

Anyone on these drugs and supplements should proceed only under doctor supervision (NIH ODS).

Who shouldn’t megadose ascorbic acid?

In the following situations, it’s best to avoid or use caution with megadosed vitamin C (NCBI):

• Individuals with kidney disease or a history of kidney stones should exercise caution as high doses of ascorbic acid acidify urine & promote stone formation (NIH ODS)
• People with blood disorders such as:
  • Thalassemia
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Sickle cell disease
  • Hemochromatosis
• Before or after angioplasty due to its potential effects on blood clotting & vascular function (NCBI)
• Diabetic patients should monitor blood sugar carefully when taking vitamin C supplements, as high doses may artificially elevate blood glucose readings (NCBI)

If you fall into those categories, certainly consult your doctor first.

Megadosed Vitamin C Questions & Answers

Questions are on the rise as interest in high-dose vitamin C increases. Here are some common ones I’ve answered for you.

Final Verdict: Is It Worth Megadosing Vitamin C?

Everyone talks about vitamin C as the “immunity vitamin.” But ascorbic acid does so much more, especially when dosed appropriately.

The evidence shows that megadosed vitamin C benefits include:

• Stronger immunity
• Better hormone levels
• Skin protection
• Faster recovery
• Accelerated wound healing
• Reduced oxidative stress
• More energy
• Improved cardiovascular health
• Therapeutic potential in severe illness

Recent findings in research point to high-dose vitamin C as one of the most underrated tools for cellular resilience.

It’s safe, orthomolecular, dirt cheap, and well documented over the decades.

If you want to go down this route, I recommend buying bulk non-GMO ascorbic acid and stacking that with a serving of whole-food-derived natural vitamin C.

That gives you the best of both worlds without the massive cost of relying exclusively on the expensive natural form.

Have you tried megadosing vitamin C? What results have you noticed in your energy, immunity, recovery, or overall health?

Share this article on your socials to help expose others to one of the simplest, low cost health optimization tools available.