Science of Vitamin C: Benefits Beyond the Common Cold
Vitamin C is so common today that it’s become a stock answer. Cold coming on? Someone will inevitably mention vitamin C.
With all this talk, how do you know you’re getting enough vitamin C? What does it do, and what are some good sources?
Here, we’ll look at major vitamin C benefits and how you can add more of it into your life.
What Is Vitamin C?
There is evidence that daily doses of vitamin C may shorten the duration and severity of colds, especially in children. Doses of 1,000-2,000 mg of vitamin C per day can help prevent colds in people who are very physically active, such as marathon runners and skiers, as well as individuals exposed to very cold environments. (Source 1)
However, most people don’t usually think of vitamin C beyond cold and flu season. This is a mistake — vitamin C is indispensable to our structural integrity, energy levels, and ability to handle stress. This nutrient even affects how we express our DNA and genes.
We can’t survive without vitamin C, and we most certainly can’t live well without adequate levels.
What is Vitamin C Good For?
What does vitamin C do and what is it good for? Vitamin C, or ascorbic acid (AA), is first and foremost an electron donor. This means it can directly donate electrons to function as an antioxidant.
Functioning as an antioxidant allows it to neutralize harmful free radicals and act as a cofactor, also donating electrons to enzymes containing iron or copper. This donation is a critical step in keeping these enzymes “active.”
Enzymes that use vitamin C as a cofactor have widespread influence on our energy levels, structural integrity, and DNA. They are involved in maintaining methylation/demethylation balance (or turning on gene expression), making collagen, and furnishing L-carnitine and norepinephrine.
Let’s review each one of these roles of Vitamin C in more detail.
Vitamin C is the most abundant water-soluble vitamin antioxidant in plasma and tissue, and one of the most famous antioxidant supplements.
Unfortunately, unlike 4,000 other species of mammals who can manufacture vitamin C, humans have lost the ability to make it because of a mutation in the gene that codes for the enzyme (L-gulonolactone oxidase or GLO). This mutation stops us from catalyzing the last step in vitamin C synthesis. (Source 2)
Our body’s inability to synthesize vitamin C has been called an “inborn error of metabolism.” Humans also have a very small capacity for storing vitamin C; we can only hold about a 30 day supply. Therefore, it is absolutely necessary to get our vitamin C from external dietary sources on a daily basis.
Antioxidant activity is a primary role of vitamin C, or l-ascorbic acid (AA). AA donates its electrons to scavenge for and neutralize reactive oxygen species (ROS) like superoxide. These free radicals are missing an electron and are extremely caustic, “rusting” everything with which they come into contact. Neutralizing them has many positive effects on overall health.
Vitamin C’s antioxidant power protects all of our cell structures, such as proteins, lipids, DNA, RNA, mitochondria and cell membranes, from oxidizing damage. Left unchecked, this damage can cause aging and inflammation.
Vitamin C is a “team player” as well, donating electrons to recycle other antioxidants like vitamin E and keeping them active to serve the same protective role in our bodies.
In the process of donating up to two electrons, vitamin C is oxidized to form dehydroascorbic acid (DHAA), which is then mostly hydrolyzed and eliminated.
Effects of Vitamin C as a Cofactor
Vitamin C is a cofactor to a variety of enzymes, donating electrons to metal-carrying enzymes called dioxygenases and monooxygenases, which use iron (Fe3+) and copper (Cu2+) at their center. In this way, it maintains the metals in their reduced state and keeps the entire enzyme active.
Enzymes, which use vitamin C as a cofactor in this manner, include those that make:
Collagen is the structural glue that holds us together as human beings. It's the basic building block of all connective tissue that builds and strengthens skin, teeth, bones, blood vessels, ligaments, and tendons. If vitamin C is completely removed from the diet, a condition called scurvy develops. You may have heard of this in history books, because it used to happen to sailors on long voyages who didn’t have access to fruits or other sources of vitamin C.
Scurvy is rare now because only very small amounts of vitamin C are needed to prevent it, but it manifests in some damaging ways without a sufficient daily intake of vitamin C. These symptoms can look like:
- Subcutaneous bleeding and bruising (due to weak blood vessels)
- Poor wound healing (from poor skin collagen)
- Joint pain and swelling (weak cartilage and ligaments)
- Thin hair and tooth loss
Vitamin C is a cofactor for the enzymes that make collagen. The enzymes proline and lysine hydroxylases (Fe2+ dependent) provide the last steps in completing the synthesis of all new collagen our bodies make and for stabilizing it’s final structure.
In addition, vitamin C is needed for proper collagen peptide gene expression. For example, in vitamin C deficiency, transcription and formation of pro-collagen (the molecule that leads to collagen) decreased by 50% in guinea pigs.(Source 3, Source 4)
It’s hugely important to support the body’s collagen production in order to to keep bones, blood vessels, and the whole body strong.
The fatigue seen in scurvy may also be due to a slowed ability to make L-Carnitine. This is a molecule that shuttles fat into mitochondria, where it is converted into energy in a process called “beta-oxidation.” Vitamin C donates electrons to the enzyme trimethyllysine hydroxylase, which makes L-carnitine.
Low levels of vitamin C may inhibit L-carnitine synthesis, causing symptoms such as lethargy. This is because without this enzyme, your body may not be able to burn fat — which will diminish fuel for energy production.
Norepinephrine (NE) is the “get up and go” or “get up and do” molecule in our bodies. It is also the main neurotransmitter of the entire Sympathetic Nervous System (SNS), the system activated when we need to get something accomplished quickly, when we are frightened or acutely stressed.
The SNS is part of our autonomic nervous system, our unconscious nervous system that keeps us breathing and our hearts beating. Vitamin C is actually helping us even during unconscious body functions.
In the Sympathetic Nervous System, our get up and go system, norepinephrine is the main neurotransmitter at postganglionic sympathetic neuron synapses. These neurons are the final connections for the messages originating in the brain and spinal cord. They link our nervous system to all of the major organs: the heart, liver, kidneys, eyes, sweat glands, and more.
When a stressful stimulus occurs, the typical responses from the SNS include increased heart rate and blood pressure, faster breathing, pupil dilation and sweating.
When faced with an immediate threat, the postganglionic SNS connection to the adrenal medulla causes more norepinephrine to be released. This is a system that creates our fight or flight response, like raising our hairs or causing our heart to pound.
Norepinephrine is also made in the brain in nuclei such as the locus coeruleus and allows us to be awake, alert, and able to retain information as well as recall memories.
So, where does this tie into ascorbic acid? Vitamin C catalyzes the monooxygenase enzymes that make norepinephrine (and dopamine) by donating electrons to the copper element Cu2+ at the core of the enzyme keeping it active.
It is not surprising, given its role in norepinephrine production, that during times of stress we use up more vitamin C and can become depleted. To make matters worse, this potentially weakens our immune responses.
The lesson to be learned is that prolonged periods of stress should be accompanied by increased intake of vitamin C. When we run low on vitamin C, we lose our pep, feeling lethargic and drained as a direct consequence of having less norepinephrine (and carnitine).
Also, because of norepinephrine’s role in the brain, you can avoid turning to the latest energy boosting product to enhance brain performance, and instead, add a few extra doses of vitamin C.
Vitamin C supplements can help if there’s a need to be alert, focused and energetic. They will help you maintain adequate levels of norepinephrine naturally and help you function at your best.
4. Genetic Expression and Regulation
Methylation involves the addition of a one-carbon (-CH3) unit to an existing molecular structure. This process regulates neurotransmitters that dictate energy and mood, hormone synthesis of estrogen, glutathione production, detoxification, immunity, and inflammation. At the DNA level, methylation is critical, and ensures stability of our genome.
When we think of methylation, we immediately associate it with the methionine cycle and its usual cofactors: B vitamins like folate (B9), methylcobalamin (B12), B5 and pyridoxine (B6), and magnesium and molybdenum.
But we need balance for every cell process, which is why the reverse process of methylation, called de-methylation, is so important. If methylation turns genes “off”, de-methylation turns genes expression and transcription back “on.” These two forces need to be balanced in order for our bodies to function well.
While methylation is dependent on B vitamins and minerals, de-methylation is dependent on vitamin C, which is a cofactor for a group of recently discovered Ten-Eleven Methylcytosine Dioxygenase Translocation de-methylation enzymes (or TET for short) (Source 5).
What does this mean? As mentioned above, the cycle of methylation and demethylation is the balance of genetic expression. It determines how we use our genes in response to our environment, a process called epigenetics. Once this balance shifts, we are exposed to a variety of serious consequences.
One example is cancer cells, which shift the balance too far off to the methylation side of the cycle. Cancer cells uniformly show low levels of de-methylation and hyper-methylated chromatin. In fact, low de-methylation can actually be measured.
Poor demethylation is evidenced by low levels of a molecule called 5-hydroxy-methyl-cytosine (5hmC). This molecule is the first step in de-methylation sequence and a recognized epigenetic marker of cancer. (Source 6) Mutations in the TET enzymes that carry out de-methylation result in hyper-methylation (over methylation) in cancer cells.
Since vitamin C is a cofactor (helper) of the TET family of enzymes which demethylate DNA, it suggests that low levels of vitamin C can contribute to the hyper-methylation found in cancer cells.
Results of studies looking at vitamin C’s role in cancer survival have been mixed, but one large meta-analysis study in breast cancer has indeed showed that higher vitamin C intake was correlated with lower mortality, both in breast cancer and overall. (Source 7)
The balance of methylation and demethylation is also important in embryos. After fertilization, embryonic development follows two rounds of methylation and demethylation. Both the maternal and paternal DNA have to be properly de-methylated for the normal process of division and growth to continue. Inadequate vitamin C levels and incomplete de-methylation can potentially lead to birth defects. (Source 5)
7 Health Benefits of Vitamin C Supplements
Vitamin C benefits range even beyond its skills as a cofactor and antioxidant. There is so much vitamin C can do for the whole body, from giving your immune system a boost to lowering the risk of stroke and diabetes.
Here are some of the most incredible benefits:
Low levels of vitamin C can result in impaired immunity and an increased risk of infection. Worse yet, infections further lower vitamin C levels as immune cells increase their use of vitamin C during the inflammatory process. (Source 8) This can become a vicious cycle of sickness and nutrient deficiency.
Ascorbic acid is required for the maturation of T lymphocytes, blood cells that help protect the body from infection. Vitamin C accumulates in neutrophils, or white blood cells, and facilitates their movement as they kill pathogens. (Source 9).
When supplemented in vitro, vitamin C has been shown to increase the number, proliferation, and function of T lymphocytes. (Source 10) This is especially important in cancer patients who are vitamin C depleted and who need to replenish their depleted populations of T lymphocytes.
Vitamin C is not just vital for cellular immunity; it also enhances another aspect of the immune system by strengthening its protective barrier function in:
- Skin – where vitamin C accumulates in keratinocytes and seems to prevent environmental oxidative damage caused by ozone. (Source 11)
- Lungs – ascorbic acid (AA) stimulates repair of the alveolar epithelial lining surface, damaged in acute lung injury caused by sepsis in mice. This protective mechanism in the lung alveolar epithelial surface was shown to be related to ascorbic acid’s ability to stimulate the rebuilding of cellular tight-junctions. (Source 12)
2. Lower Risk of Heart Failure and Cardiovascular Disease
Vitamin C has been studied extensively both in retrospective and prospective fashion. Retrospective studies look back and observe patterns based on answered questions about vitamin C consumption. Prospective studies look forward at correlations between higher levels of vitamin C as measured in plasma and certain diseases or high risk factors.
There is evidence from prospective cohort studies that vitamin C, as measured by plasma levels, is associated with a lower risk of cardiovascular risk factors like high blood pressure, coronary vessel disease, and stroke. Higher food sourced vitamin C intake and higher supplement based vitamin C intake (>700 mg per day) have both been shown to decrease the risk of coronary heart disease. (Source 13, Source 14)
The endothelium is the lining of our blood vessels, and in normal function it responds to the tissue’s increased oxygen demand by dilating blood vessels. It does this via a nitric oxide-mediated system that then causes increased blood flow (vasodilation).
In cases of endothelial dysfunction, the function of the endothelium becomes compromised. This endothelial dysfunction is directly related to the increased risk of heart attacks. (Source 15)
A meta-analysis of 44 studies using vitamin C concluded that vitamin C supplementation in any form had a beneficial effect on endothelial function (EF), and an improved ejection fraction (EF) — which is an important number doctors, such as cardiologists, use to measure the strength of the heart muscle. (Source 16) The ejection fraction measures how much of the volume of blood in the ventricle the heart can pump out with every contraction.
Amazingly, vitamin C appeared to have the highest benefit in those with higher cardiovascular risk.
These studies were also validated by a prospective study involving more than 20,000 men and women whose plasma vitamin C levels were followed long term. This study showed that the higher the plasma vitamin C levels were, the lower the risk of heart failure. Every 20 μmol/L increase in plasma vitamin C levels was correlated with a 9% lower risk of heart failure. (Source 17)
3. Protection During Coronary Angioplasty Procedures
Coronary arteries are the arteries that supply the heart muscle with blood and oxygen. These arteries can become occluded causing myocardial infarction (heart attack) when the heart muscle stops receiving blood. Coronary angioplasty is a procedure where a balloon is inserted inside the blood vessel to gradually stretch it open again and reestablish blood flow.
Although meant to help the heart, coronary angioplasty can itself actually be associated with damage to heart muscle cells in as many as one third of the procedures. A study of 532 patients scheduled to undergo coronary angioplasty showed that three grams of intravenous vitamin C given in the six hours before the procedures significantly prevented heart muscle injury. (Source 18)
4. Lowered Risk of Stroke and Diabetes
Beyond lowering your risk for sickness, heart failure, cardiovascular disease, and heart muscle cell damage, vitamin C can also reduce the chances of stroke and diabetes. In a Japanese study following 880 healthy individuals over 20 years, higher levels of plasma vitamin C were strongly associated with a lower risk of all types of stroke. (Source 19)
A similar study involved over 20,000 participants who were healthy at baseline and were followed for 10 years. In those whose vitamin C levels were in the top 25%, the incidence of stroke was 42% lower compared to those in the lowest 25% of vitamin C consumption. (Source 20)
A strong inverse correlation between vitamin C plasma levels and the risk of developing diabetes was discovered in a prospective study of over 20,000 participants followed over 10 years. Those with the highest levels of vitamin C had the lowest risk of developing diabetes. (Source 21)
5. Skin Protection
Skin is composed of the superficial layer called the epidermis and the deeper layer underneath called the dermis, both of which house vitamin C.
Vitamin C levels in skin are actually much higher than those circulating in blood. This suggests that vitamin C accumulates in skin preferentially. (Source 22) However, levels decrease with age, as well as with exposure to pollutants like UV light and cigarette smoke.
The upper layer of skin, the epidermis, contains cells called keratinocytes which are responsible for maintaining the barrier function of the skin. Prolonged exposure to UV sunlight is damaging to keratinocytes, causing an increase in free radical formation. This process oxidizes and damages DNA and lipids in keratinocytes, depleting their levels of Vitamin C in the process. (Source 23)
Keratinocytes increase their ability to take up vitamin C in a protective response to UV light exposure, so can topical Vitamin C application help with sun damage? It does seem that vitamin C protection can be derived from placing it directly on skin. A topical solution of vitamin C (15%) combined with vitamin E has been shown to be effective against countering the DNA damage associated with skin cancer in UV light treated skin. (Source 24)
The deeper layer of skin, called the dermis, contains high levels of collagen. Collagen is constantly broken down while fibroblast cells in the dermis layer make new collagen. As mentioned, without vitamin C, the process of making new collagen would stop in its tracks.
In addition to the actual synthesis of collagen for a healthy dermis and skin, vitamin C also works to promote and initiate collagen formation at the DNA level by boosting gene transcription. Furthermore, vitamin C provides stabilization of collagen mRNA and synthesis of the pro-collagen molecule, resulting in an overall increase in total collagen synthesis in skin.
An undesirable effect of UV light exposure is the overproduction of elastin, giving skin too much laxity. Vitamin C decreases elastin production while stimulating collagen synthesis, preventing this from occurring. (Source 25)
So, does topical vitamin C or a dietary supplement provide better protection from laxity and wrinkles?
Both seem effective. Several studies have shown that topical vitamin C applications can reduce the appearance of wrinkles in as little as 12 weeks. (Source 26) However, the effect of topical vitamin C was not seen in a study of post-menopausal women who already had high oral consumption of vitamin C. (Source 27) This suggests the effect on wrinkle prevention can also be achieved from within, simply through higher oral intake of vitamin C.
6. Wound Healing
Skin wounds require collagen synthesis and vitamin C to heal properly. Impaired wound healing is an indication of low levels of vitamin C, and supplementation with both oral and topical vitamin C is useful especially in individuals who may have a low vitamin C level baseline (such as smokers and heavy drinkers).
Smokers in particular have lower levels of vitamin C than nonsmokers, as well as slower healing. This fact is corrected with smoking cessation and improvement in baseline plasma vitamin C levels. (Source 28) The National Institutes of Health states that Vitamin C also boosts iron absorption, another nutrient necessary in wound healing.
Vitamin C supplementation does not necessarily hasten wound healing especially if we already have adequate intake, but it can certainly do so in individuals with lower vitamin C levels. It may also reduce scarring, as seen in one Asian population study. Topical application of vitamin C in a silicone gel significantly reduced permanent scar formation and pigmentation. (Source 27)
Vitamin C is required for the norepinephrine (NE) production mentioned above. In the setting of sepsis, IV norepinephrine drips in the intensive care unit are often required to support healthy blood pressure. Moreover, patients in sepsis and septic shock have very low levels of vitamin C, as has been used up due to increased oxidative stress and metabolic needs such as NE production. (Source 30)
In a study of 28 ICU patients with sepsis and shock, when 25 mg/kg of vitamin C IV was given every 6 hours, it reduced the dose of IV norepinephrine needed to maintain blood pressure. Even more importantly, it also reduced the 28-day mortality of these patients to 14% in the group receiving the vitamin versus 64% in the group which did not receive IV vitamin C.
Vitamin C vs. Cancer
What can’t vitamin C do? Could this everyday vitamin even help treat cancer?
This question became a topic of debate in 1976 through Linus Pauling, a double Nobel Prize winner. Pauling showed a 4.2 times longer survival time for terminal cancer patients who received 10 grams (10,000 mg) of intravenous (IV) vitamin C per day for 10 days, followed by 10 grams of oral vitamin C per day indefinitely. (Source 31)
Interestingly, this experiment could not be duplicated with a high oral dose of vitamin C alone. It was later discovered the route of administration of high dose vitamin C is the key factor. High doses of IV vitamin C behave very differently than high doses of oral vitamin C.
Here is the simple difference between oral and IV vitamin C supplementation:
- Taken in high oral doses, Vitamin C behaves as an antioxidant.
- When taken in high IV doses, Vitamin C becomes a pro-oxidant, acting as a metabolic stressor to cancer cells
- IV vitamin C supplementation has effects similar to standard chemotherapy, but with very few side effects.
To understand this further, it is useful to first explain bioavailability or how vitamin C plasma levels vary depending on route of administration.
Delivering Vitamin C Benefits Intravenously
When taken by mouth, vitamin C shows rapid absorption up to doses of 200 mg at a time. Doses above this level are generally poorly absorbed by intestinal system cells using the sodium dependent vitamin C transporters type 1.
Our bodies exercise high levels of control over the blood levels of vitamin C, maintaining a “steady state” between 60-80 μmol/L concentration in plasma. This “micromolar” level represents the upper range of what we can achieve by taking vitamin C orally. Large doses of plain vitamin C cause GI distress like abdominal cramping and diarrhea. Patients will not achieve higher blood concentration levels regardless of how high the oral dose is, because our bodies regulate absorption to these steady levels.
On the other hand, intravenous sources of vitamin C completely bypass the intestinal absorption limitations of oral vitamin C and the tight control based on plasma levels. IV vitamin C achieves blood concentration levels between 100-1,000 times higher than oral vitamin C!
IV vitamin C infusions between 25-100 grams are considered to be high-dose IV vitamin C. These will achieve plasma levels of 1-10 mM, or “macro molar” concentrations. 1-10 mM and is equivalent to 100-1000 μmol/L, making this a dramatically higher amount available.
Other forms of vitamin C, such as liposomal vitamin C, which also do not rely on the intestinal vitamin C transporter, increase the plasma levels of vitamin C when compared to an equivalent dose of plain vitamin C, but are still far lower than those achieved by IV infusion. (Source 32)
What Does Vitamin C Do to Cancer?
So what does vitamin C do for cancer? When different types of cancer cells are exposed to “macro molar” vitamin C levels, they are placed under stress and begin to die. Three-dimensional models of prostate, breast, ovarian and other types of cancer cells in vitro show that the higher the dose of vitamin C they are exposed to, the more their growth is inhibited and the tumor mass shrinks.
Vitamin C in these “macro molar” concentrations (which can only be achieved with IV vitamin C administration) has a direct cytotoxic effect on tumor cells. This high dose induces high levels of hydrogen peroxide in the extracellular space but not in whole blood.
For example, in a study using cancer cell cultures exposed to high “macro molar” concentrations of vitamin C (1-10 mM), the authors noted that both extracellular and intracellular H2O2 increased dramatically. (Source 33)
This is not limited to cells in a laboratory. When rats were given the equivalent doses of IV vitamin C in humans, their levels of hydrogen peroxide did indeed spike, but only between cells — or in the so called “extracellular” space.
In addition to generating hydrogen peroxide in the extracellular space, the vitamin C content administered through IV also induced the production of vitamin C radical Asc (•). This is a pro-oxidant “free radical” that forms when vitamin C readily donates electrons to the iron (Fe3+) present in extracellular proteins that contain it.
Once reduced, iron donates its electron to oxygen, thus creating superoxide, which quickly combines with hydrogen to form hydrogen peroxide, thus explaining how H2O2 levels spike. Cancer cells are more susceptible to damage from hydrogen peroxide because they lack the enzyme “catalase” which renders H202 harmless by turning it into water, H20. (Source 34)
IV administration of high doses of vitamin C is proven to help treat cancer. However, these effects of raising hydrogen peroxide and ascorbate radical at “macro molar” blood levels are only achievable by giving vitamin C as an IV. They cannot be reproduced with oral vitamin C.
Glutathione, Ascorbic Acid, and Hydrogen Peroxide
The presence of high levels of hydrogen peroxide quickly depletes “active” reduced glutathione (GSH) and turns it into oxidized “inactive” glutathione (GSSG). This causes levels of hydrogen peroxide to increase dramatically because GSH is no longer available to buffer H2O2. (Source 35)
Once the protective effect of glutathione in mitochondria and cell structures is removed, hydrogen peroxide and ascorbate radicals begin to damage the DNA of cancer cells. In addition they also reduce ATP production, leading to cancer cell death.
The temporary depletion of intracellular reduced (active) glutathione is key here and it’s the reason why oral or IV glutathione should be avoided in conjunction with high dose IV vitamin C (HDVIC). (Source 35).
Depleting “active” reduced glutathione, converting it to oxidized “inactive glutathione, and allowing hydrogen peroxide to wreak havoc on cancer cells is part of the power of IV treatments of vitamin C for cancer.
IV Vitamin C Treatment in Humans
The Riordan Clinic in Wichita, Kansas, has spearheaded the investigation into the mechanisms and safety of IV vitamin C infusions in cancer patients. Beginning in the early 80s with Dr. Hugh D. Riordan, the center has published research and treatment on many conditions like Lyme, viral infections, pain, and cancer.
The Riordan Clinic high dose IV vitamin C protocol is still considered by many to be the standard for the high dose IV vitamin C (HDIVC) therapy. (Source 36)
Riordan Clinic’s research has shown that IV vitamin C:
- Helps cancer patients with depleted plasma vitamin C levels
- Decreases angiogenesis, or the growth of new blood vessels, that feed further growth of tumors
- Decreases inflammation, lowers CRP and pro-inflammatory cytokines (such as TNF-alpha, IL-2 and IL-8)
- Increases a sense of wellbeing in cancer patients
Many other small-scale clinical trials have since also validated Riordan Clinic’s findings.
In a 2015 Phase 1-2 study, 15 patients with various types of advanced cancer received HDIVC in conjunction with chemotherapy. 6 patients showed no changes. 6 other patients showed temporary stabilization of their disease, and 3 patients actually showed unusually favorable results, stabilizing for up to a year and a half and even seeing regression of their cancer. (Source 37)
This is a typical distribution that we have also seen in our clinic. Just as with chemotherapy, not everyone responds to IV vitamin C in the same way. Furthermore, different cancer cell types have various sensitivities to high doses of IV vitamin C.
Additional conclusions derived from this clinical High Dose IV Vitamin C study were:
- High dose IV vitamin C 50-120 grams (1.5 gms/kg body weight) was well tolerated.
- Vitamin C IV is non-toxic and did not increase cancer risk.
- Short-term tissue retention of the vitamin C following chemotherapy showed no increase of uric acid, the compound feared to form kidney stones
Other studies have shown that IV vitamin C infusions are safe to use in conjunction with traditional chemotherapy, like gemcitabine and erlotinib, for pancreatic cancer. (Source 38) HDVIC is also associated with decreased toxicity associated with chemotherapy, including lessened fatigue, nausea, insomnia, constipation and depression. (Source 39)
In certain instances, as with ovarian cancer, using HDVIC has been shown to actually increase the effectiveness of traditional chemotherapeutic pro-oxidative chemotherapy agents, like carboplatin and paclitaxel. This is one situation in which IV vitamin C may inhibit ovarian cancer cell growth. (Source 40)
Mainstream Acceptance of High Dose IV Vitamin C
IV vitamin C infusions in the context of cancer are becoming more common and accepted as feasible as adjuncts to traditional cancer treatments.
The National Cancer Institute’s reference on high dose IV vitamin C (HDIVC) webpage states: (Source 41)
- High dose IV vitamin C is well tolerated alone or in conjunction with other standard cancer therapies.
- Studies have shown that HDIVC improves quality of life and decreases cancer-related toxicities.
- HDIVC appears promising and more research needs to be done with rigorous trials.
Vitamin C Deficiency
As we’ve discussed, the effects of this nutrient are astounding, but what happens if you aren’t getting the recommended dietary allowance (RDA)?
The Food and Drug Administration lists vitamin C as an often-deficient nutrient. You’re missing out on some astounding benefits, and without the right amount of vitamin C, you could be at risk of some unfortunate side effects.
Measuring Vitamin C Levels
Blood levels of vitamin C are measured in “micromolar” (μmol/L) units and are as follows:
- Severe deficiency: plasma concentrations < 11 μmol/L
- Marginally deficient: plasma concentrations < 23 μmol/L
- Optimal levels: plasma concentrations > 50 μmol/L
Very few doctors today actually test vitamin C levels even though epidemiologic studies have shown that vitamin C deficiency, or hypovitaminosis C, is very common. This state is defined as blood levels less than 11 plasma vitamin C (< 11 μmol/L).
Unsurprisingly, vitamin C deficiency is the fourth-leading vitamin deficiency in the United States. (Source 42)
Is Vitamin C Deficiency Affecting Me?
Vitamin C deficiency is common. A 2009 study of 7,277 participants showed that 7.1% of individuals were vitamin C deficient. (Source 42) The Linus Pauling Institute recommends a minimum intake of 400 mg per day for healthy adults.
However, some people are at a high risk for low levels of vitamin C, based on age, lifestyle, and illnesses. Individuals with higher risk for developing a vitamin C deficiency are:
- Smokers. These patients need higher levels of vitamin C intake due to increased oxidative stress. The more cigarettes smoked, the lower the level of vitamin C (Source 41, Source 29)
- Regular alcohol users. This demographic has low leukocyte vitamin C levels (Source 43)
- The elderly. There is evidence that aging animal liver cells have significantly decreased SCVT1 vitamin C transporters and cellular uptake (Source 44). This can prohibit vitamin C from getting to or permeating the cells.
- Cancer patients. Most cancer patients have low levels of vitamin C, and chemotherapy and radiation further lower these levels due to increased oxidative stress.
- Individuals with chronic disease and malabsorption issues.
The Best Vitamin C Sources
IV supplementation is not the only way to get your daily intake of vitamin C. It’s always wise to eat a balanced, nutrient-rich diet and to supplement if necessary.
Below, we’ll list the foods and supplements that can help you stay full of vitamin C.
Foods High In Vitamin C
You may be wondering: which foods are high in vitamin C? Many fruits and plants contain high doses of vitamin C, especially citrus fruits. Among the richest sources are:
- Kiwifruit: 70 mg in a medium-sized fruit
- Grapefruit: 48 mg in a medium-sized fruit
- Oranges: 70 mg in one medium fruit
- Bell peppers: 60 mg in a ½ cup of green pepper, and 95 mg in ½ cup of red pepper (also a good source of beta-carotene)
- Broccoli: 39 mg in ½ cup
- Brussels sprouts: 37 mg in ½ cup
- Apples: 11 mg in one fruit
- Bananas: 10 mg in one medium banana
The Best Vitamin C Supplements
Our diets are certainly the first and best “go to” modifications we can make to increase our vitamin C levels, especially during times of stress, infections, or physical trauma such as wounds, surgery, or UV overexposure.
Additional supplementation with ascorbic acid or one of its salts, such as sodium or calcium ascorbate, is also an alternative. This works especially well for those of us who tend to get upper respiratory illnesses often or are performance athletes.
2-3 grams (2000-3000 mg) of vitamin C can reduce the frequency and severity of colds when taken daily.
However, plain vitamin C has a tendency to be poorly absorbed. I recommend a liposomal formulation of vitamin C because of the enhanced absorption it provides when compared to simple vitamin C powder.
Liposomes are microscopic spheres with a shell made up of the same natural building blocks as our own cell membranes, called phospholipids. The center of the liposomes contains and protects the vitamin C needed.
Additionally, the phospholipids making the outer shell of the liposomes are predominantly made up of phosphatidylcholine (PC), a rich source of choline.
Choline is a precursor for acetylcholine (Ach) a neurotransmitter which helps improve cognition and memory. PC and choline are also integral players in liver health and help provide methyl donors for the methylation cycle. For all these reasons and more, I recommend liposomal vitamin C.
- Vitamin C aids in more than just immunity. It also helps to avoid diabetes, protects against heart disease and stroke, and is vital for skin health and wound healing.
- Without vitamin C, we cannot make collagen and our bodies begin to break down. This results in unhealthy bones, frail tendons, and ligaments, skin, teeth, gums, and blood vessels.
- Norepinephrine is an essential neurotransmitter that controls attention and memories in our brains. It’s responsible for delivering our response to stress, and it’s made with the help of vitamin C.
- Prolonged stress depletes norepinephrine, and vitamin C is needed to replenish it and avoid fatigue.
- Energy from the fat your body burns is dependent on a molecule called L-carnitine, and L-carnitine synthesis is dependent on vitamin C. Low L-carnitine levels can also manifest as chronic fatigue.
- Vitamin C has a direct effect on epigenetics, turning on gene expression and maintaining the methylation and demethylation cycle.
- There’s a big difference between oral and intravenous (IV) vitamin C. High IV doses will turn vitamin C from an antioxidant into an oxidant, releasing hydrogen peroxide (H2O2) and vitamin C free radicals in the extracellular space.
- This oxidative effect from IV vitamin C fights cancer cells, much like chemotherapy but without serious reactions, and can even diminish traditional cancer treatment’s side effects of fatigue.
- Large oral doses of Vitamin C are poorly absorbed because of easily saturated transporters in the gut.
- Higher absorption can be achieved with liposomal vitamin C , which achieves blood levels 100-1,000 times those seen with simple oral vitamin C supplementation.
- Hemilä, H., & Chalker, E. (2013). Vitamin C for preventing and treating the common cold. Cochrane database of systematic reviews, (1). Abstract: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000980.pub4/full
- Drouin, G., Godin, J. R., & Pagé, B. (2011). The genetics of vitamin C loss in vertebrates. Current genomics, 12(5), 371-378. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145266/
- May, J. M., & Harrison, F. E. (2013). Role of vitamin C in the function of the vascular endothelium. Antioxidants & redox signaling, 19(17), 2068-2083. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869438/
- Mahmoodian, F., & Peterkofsky, B. (1999). Vitamin C deficiency in guinea pigs differentially affects the expression of type IV collagen, laminin, and elastin in blood vessels. The Journal of nutrition, 129(1), 83-91. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/9915880
- Camarena, V., & Wang, G. (2016). The epigenetic role of vitamin C in health and disease. Cellular and Molecular Life Sciences, 73(8), 1645-1658. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805483/
6.Lian, C. G., Xu, Y., Ceol, C., Wu, F., Larson, A., Dresser, K., ... & Lee, C. W. (2012). Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell, 150(6), 1135-1146. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/22980977/
- Harris, H. R., Orsini, N., & Wolk, A. (2014). Vitamin C and survival among women with breast cancer: a meta-analysis. European journal of cancer, 50(7), 1223-1231. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/24613622
8.Carr, A., & Maggini, S. (2017). Vitamin C and immune function. Nutrients, 9(11), 1211. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707683/
- Fernandes, J., Arida, R. M., & Gomez-Pinilla, F. (2017). Physical exercise as an epigenetic modulator of brain plasticity and cognition. Neuroscience & Biobehavioral Reviews, 80, 443-456. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705447/
- Klein, R. W., Van, C. E., Wieten, L., Germeraad, W. T. V., & Bos, G. M. J. (2018). Influence of Vitamin C on Lymphocytes: An Overview. Antioxidants (Basel, Switzerland), 7(3). Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874527/
- Valacchi, G., Sticozzi, C., Belmonte, G., Cervellati, F., Demaude, J., Chen, N., ... & Oresajo, C. (2015). Vitamin C compound mixtures prevent ozone-induced oxidative damage in human keratinocytes as initial assessment of pollution protection. PLoS One, 10(8), e0131097. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536008/
- Fisher, B. J., Kraskauskas, D., Martin, E. J., Farkas, D., Wegelin, J. A., Brophy, D., ... & Natarajan, R. (2012). Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. American Journal of Physiology-Lung Cellular and Molecular Physiology, 303(1), L20-L32. Full text: https://www.ncbi.nlm.nih.gov/pubmed/22523283
- Ye, Z., & Song, H. (2008). Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. European Journal of Cardiovascular Prevention & Rehabilitation, 15(1), 26-34. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/18277182
- Knekt, P., Ritz, J., Pereira, M. A., O'Reilly, E. J., Augustsson, K., Fraser, G. E., ... & Pietinen, P. (2004). Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts. The American journal of clinical nutrition, 80(6), 1508-1520. https://www.ncbi.nlm.nih.gov/pubmed/15585762
- Matsuzawa, Y., Kwon, T. G., Lennon, R. J., Lerman, L. O., & Lerman, A. (2015). Prognostic value of flow‐mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta‐analysis. Journal of the American Heart Association, 4(11), e002270. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/26567372
- Ashor, A. W., Lara, J., Mathers, J. C., & Siervo, M. (2014). Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials. Atherosclerosis, 235(1), 9-20. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/24792921
- Pfister, R., Sharp, S. J., Luben, R., Wareham, N. J., & Khaw, K. T. (2011). Plasma vitamin C predicts incident heart failure in men and women in European Prospective Investigation into Cancer and Nutrition–Norfolk prospective study. American heart journal, 162(2), 246-253. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/21835284
- Wang, Z. J., Hu, W. K., Liu, Y. Y., Shi, D. M., Cheng, W. J., Guo, Y. H., ... & Zhou, Y. J. (2014). The effect of intravenous vitamin C infusion on periprocedural myocardial injury for patients undergoing elective percutaneous coronary intervention. Canadian Journal of Cardiology, 30(1), 96-101. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/24365194
- Yokoyama, T., Date, C., Kokubo, Y., Yoshiike, N., Matsumura, Y., & Tanaka, H. (2000). Serum vitamin C concentration was inversely associated with subsequent 20-year incidence of stroke in a Japanese rural community: the Shibata study. Stroke, 31(10), 2287-2294. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/11022052
20.Myint, P. K., Luben, R. N., Welch, A. A., Bingham, S. A., Wareham, N. J., & Khaw, K. T. (2008). Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer–Norfolk prospective population study. The American journal of clinical nutrition, 87(1), 64-69. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/18175738
- Harding, A. H., Wareham, N. J., Bingham, S. A., Khaw, K., Luben, R., Welch, A., & Forouhi, N. G. (2008). Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer–Norfolk prospective study. Archives of internal medicine, 168(14), 1493-1499. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/18663161
- Pullar, J., Carr, A., & Vissers, M. (2017). The roles of vitamin C in skin health. Nutrients, 9(8), 866. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579659/
- Stewart, M. S., Cameron, G. S., & Pence, B. C. (1996). Antioxidant nutrients protect against UVB-induced oxidative damage to DNA of mouse keratinocytes in culture. Journal of Investigative Dermatology, 106(5), 1086-1089. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/8618044
- Murray, J. C., Burch, J. A., Streilein, R. D., Iannacchione, M. A., Hall, R. P., & Pinnell, S. R. (2008). A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. Journal of the American Academy of Dermatology, 59(3), 418-425. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/18603326
- Davidson, J. M., LuValle, P. A., Zoia, O., Quaglino, D., & Giro, M. (1997). Ascorbate differentially regulates elastin and collagen biosynthesis in vascular smooth muscle cells and skin fibroblasts by pretranslational mechanisms. Journal of Biological chemistry, 272(1), 345-352. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/8995268
- Raschke, T., Koop, U., Düsing, H. J., Filbry, A., Sauermann, K., Jaspers, S., ... & Wittern, K. P. (2004). Topical activity of ascorbic acid: from in vitro optimization to in vivo efficacy. Skin pharmacology and physiology, 17(4), 200-206. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/15258452
- Nusgens, B. V., Colige, A. C., Lambert, C. A., Lapière, C. M., Humbert, P., Rougier, A., ... & Creidi, P. (2001). Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. Journal of Investigative Dermatology, 116(6), 853-859. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/11407971
- Sørensen, L. T., Toft, B. G., Rygaard, J., Ladelund, S., Paddon, M., James, T., ... & Gottrup, F. (2010). Effect of smoking, smoking cessation, and nicotine patch on wound dimension, vitamin C, and systemic markers of collagen metabolism. Surgery, 148(5), 982-990. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/20347467
- Schectman, G., Byrd, J. C., & Gruchow, H. W. (1989). The influence of smoking on vitamin C status in adults. American Journal of Public Health, 79(2), 158-162. Abstract: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1349925/
- Zabet, M. H., Mohammadi, M., Ramezani, M., & Khalili, H. (2016). Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock. Journal of research in pharmacy practice, 5(2), 94. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/27162802
- Cameron, E., & Pauling, L. (1976). Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proceedings of the National Academy of Sciences, 73(10), 3685-3689. Abstract: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC431183/
- Davis, J. L., Paris, H. L., Beals, J. W., Binns, S. E., Giordano, G. R., Scalzo, R. L., ... & Bell, C. (2016). Liposomal-encapsulated ascorbic acid: Influence on vitamin C bioavailability and capacity to protect against ischemia–reperfusion injury. Nutrition and metabolic insights, 9, NMI-S39764. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/27375360
- Park, S. (2013). The effects of high concentrations of vitamin C on cancer cells. Nutrients, 5(9), 3496-3505. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798917/
- Chen, Q., Espey, M. G., Sun, A. Y., Lee, J. H., Krishna, M. C., Shacter, E., ... & Levine, M. (2007). Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proceedings of the National Academy of Sciences, 104(21), 8749-8754. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885574/
- Chen, P., Stone, J., Sullivan, G., Drisko, J. A., & Chen, Q. (2011). Anti-cancer effect of pharmacologic ascorbate and its interaction with supplementary parenteral glutathione in preclinical cancer models. Free Radical Biology and Medicine, 51(3), 681-687. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/21672627
- Riordan, H. D. (2014). The Riordan intravenous vitamin C (IVC) protocol for adjunctive cancer care: IVC as a chemotherapeutic and biological response modifying agent. The orthomolecular treatment of chronic disease”, edited by AW Saul, Basic Health Publications, Inc, 750-766. Full text: https://riordanclinic.org/wp-content/uploads/2015/11/RiordanIVCprotocol_en.pdf
- Hoffer, L. J., Robitaille, L., Zakarian, R., Melnychuk, D., Kavan, P., Agulnik, J., ... & Miller Jr, W. H. (2015). High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PloS one, 10(4), e0120228. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388666/
- Monti, D. A., Mitchell, E., Bazzan, A. J., Littman, S., Zabrecky, G., Yeo, C. J., ... & Levine, M. (2012). Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PloS one, 7(1), e29794. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260161/
- Fritz, H., Flower, G., Weeks, L., Cooley, K., Callachan, M., McGowan, J., ... & Seely, D. (2014). Intravenous vitamin C and cancer: a systematic review. Integrative cancer therapies, 13(4), 280-300. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/24867961
- Ma, Y., Chapman, J., Levine, M., Polireddy, K., Drisko, J., & Chen, Q. (2014). High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Science translational medicine, 6(222), 222ra18-222ra18. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/24500406
- Integrative, P. D. Q. (2013). High-Dose Vitamin C (PDQ®). In PDQ Cancer Information Summaries [Internet]. National Cancer Institute (US). Full text: https://www.cancer.gov/about-cancer/treatment/cam/patient/vitamin-c-pdq
- Schleicher, R. L., Carroll, M. D., Ford, E. S., & Lacher, D. A. (2009). Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003–2004 National Health and Nutrition Examination Survey (NHANES). The American journal of clinical nutrition, 90(5), 1252-1263. https://www.ncbi.nlm.nih.gov/pubmed/19675106
- Baines, M. (1982). Vitamin C and exposure to alcohol. International journal for vitamin and nutrition research. Supplement= Internationale Zeitschrift fur Vitamin-und Ernahrungsforschung. Supplement, 23, 287-293. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/6126460
- Michels, A. J., Joisher, N., & Hagen, T. M. (2003). Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes. Archives of biochemistry and biophysics, 410(1), 112-120. Abstract: https://www.ncbi.nlm.nih.gov/pubmed/12559983