FoundMyFitness - #054 Vitamin C: Oral vs. Intravenous, Immune Effects, Cancer, Exercise Adaptation & More

Episode Date: May 13, 2020

In this episode, Dr. Rhonda Patrick discusses all things vitamin C. This episode covers oral bioavailability, intravenous vitamin C bioavailability, immune cell function, common cold and other viral infections, lung function, sepsis, pneumonia, inflammation, intravenous vitamin C and cancer, role in exercise, safety concerns, and so, so much more! In this episode, you'll discover: (00:00) Introduction (07:33) Background on vitamin C, an antioxidant and immune booster (17:09) Bioavailability of vitamin C and dose frequency (22:53) Vitamin C in the context of the common cold (28:09) Vitamin C improves lung function and immunity (35:54) Vitamin C and exercise - does it blunt exercise adaptation? (45:51) Vitamin C and fatty acid oxidation, including relevance in obesity (48:44) Vitamin C and the brain - memory, learning, and executive function (51:15) Intravenous Vitamin C and its use for the treatment of certain kinds of infection (55:33) Intravenous Vitamin C as an adjunct cancer therapy (57:40) Effect of Vitamin C on fertility and reproduction (58:36) Intravenous vitamin C and cardiovascular health (01:00:42) Vitamin C and inflammation (01:02:38) Vitamin C's mechanisms of action  (01:08:34) Intravenous and Oral vitamin C safety (01:10:20) Vitamin C intake and kidney stone risk (01:13:57) Conclusions If you're interested in learning more, you can read the full show notes here. Join over 300,000 people and get the latest information straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

Hello everyone. Today I'm going to talk to you about vitamin C, a vitamin that nearly everyone has heard about for its potent immunity boosting qualities. Although I've been wanting to talk to you in a comprehensive way about vitamin C for a long time, the timing of this podcast released in the midst of a global pandemic might be just a little bit serendipitous. Despite the serendipity, it's really important that we emphasize that this conversation, even though it brushes up against topics like improved viral immunity is not meant to suggest in any way that vitamin C is somehow an outright cure for COVID-19. There's just no evidence of that yet. It's really important to say that in the background of everything going on in the world right now. Trials are ongoing to see if there's a role,

particularly for intravenous administration, but the data isn't there yet. The entire research community is scrambling, looking for serious treatments for people often in life-threatening conditions. Let's support them as a community by taking that search seriously and soberly approaching the evidence as it exists rather than as we'd like it to be. Having said that, my hope is to at least overturn some of the contention that Dr. Linus Pauling, a brilliant figure well-known in the vitamin C world, was somehow a little bit off his rocker in old age. For those of you who don't know, Dr. Pauling was the Nobel Prize-winning chemist who found clinical evidence suggesting that high-dose intravenous administration of vitamin C is useful as a supportive

treatment for cancer, as well as a method for mitigating the side effects of chemotherapy. In other words, Pauling was the vitamin C guy. While it may be undeniable that when it came to vitamin C, Pauling was definitely, shall we say, an enthusiast, at least one of the problems of critiques of his, work on vitamin C is the apples to oranges comparison of his claims, which often used intravenous dosing, with that of research on oral dosing. Oral and intravenous supplementation of vitamin C, both potentially merit-worthy in different contexts, are in some ways worlds apart in biological activity because of the sheer concentrated increase in plasma levels that happens when you take

something intravenously. If a person eats between five and nine servings of biolns, vitamin C rich fruits and vegetables a day, their steady-state plasma vitamin C concentrations will be around 80 micromoles per liter or less. A person's peak plasma vitamin C concentrations won't exceed 220 micromoles per liter from oral vitamin C intake, even if they take a maximum oral dose of 3 grams six times daily. By contrast, intravenous vitamin C can produce plasma concentrations as high as 15,000 micromoles per liter. There are three important things to take home from that statement. First, there is a maximum plasma concentration of vitamin C achieved orally,

which is 220 micromole per liter of blood. Second, three grams of oral vitamin C taken six times per day can sustain maximum plasma levels, whereas a single three gram dose cannot. third, the maximum plasma vitamin C concentration from intravenous vitamin C can be as high as 15,000 micromoles per liter, which is 68 times higher than can be achieved through oral consumption. I'll go into more specifics on this study later in the podcast. But I digress. In today's discussion of vitamin C will cover a few broad areas. I'll give you a general overview of vitamin C that includes food sources of vitamin C,

recommended oral intakes, which vary across the lifespan, and what happens when a person is deficient? I'll talk about the many roles, and there's a lot, that vitamin C plays in the body, especially as a co-factor, in antioxidant, and as a critical component of immune function. I'll describe the metabolic disposition of vitamin C, in other words, how the body metabolizes the vitamin and where it ends up, which is quite a bit different from most other small molecules. Then I'll talk about some really interesting data on intravenous administration of vitamin C. Although it's not the typical means of getting this essential vitamin, it offers promise as a therapeutic strategy against cancer and some other serious health concerns. As I alluded to earlier, I'll drill down

on the role that vitamin C plays in viral defense. Then I'll get into some really cool stuff, some of which was news to me, like differences in bioavailability in the various forms of vitamin C, and whether oral liposomal vitamin C is better than the regular oral form. I'll bring up some concerns about whether vitamin C can blunt the effects of exercise, especially in terms of mitochondrial biogenesis and function, improved insulin sensitivity, glucose utilization, and enhanced immune function. I'll describe some of the ways in which vitamin C can improve outcomes of severe viral infections in ways you might not have thought about, like reducing the number of days spent on mechanical

ventilation. I'll talk about how vitamin C plays a role in fatty acid oxidation, which could have implications for people trying to lose weight. I'll also address one of the big questions that people often have about vitamin C. Does it cause kidney stones? Of course, I'd be remiss if I didn't talk about safety, so I'll discuss that too. And absolutely no discussion about vitamin C would be complete without mentioning the common cold. It's probably the most extensively studied infection regarding the effects of vitamin C. Most of the controlled trials used a pretty modest dose of just one gram per day. But before we get started, I want to quickly mention a couple of things. My team and I literally spent several months combing over the scientific literature on vitamin C. We read hundreds of studies,

peer-reviewed each other's conclusions, went through study design and methods with a fine comb in order to get to the bottom of inconsistent findings. We went through dozens and dozens of rough drafts and finally published a 28-page article with 190 references on all things vitamin C. This episode you're listening to is actually a derivative of that document. You can find that amazing, fully referenced article on the website in the topic section, or by just hitting Google and searching Found My Fitness, Vitamin C. That's Found My Fitness, Vitamin C. Creating podcasts and resources like these are a monumental effort.

One of the really cool ways we've devised to do this type of work is to offer a premium membership option. If you appreciate the work we are doing at Found My Fitness, this is a great way to give back and actually get a plethora of great benefits that get better by the day. For example, twice per month we send out a special email with write-ups on recent science news or things that piqued the team's interest. In fact, there's a lot of other great benefits. If you would like to take a moment and check out the great offering we are growing for our audience, I'd so appreciate it. It really is getting better all of the time. You can find more information on that at foundmyfitness.com forward slash premium. That's foundmyfitness.com forward slash P-R-E-M-I-U-M premium. Now on to the podcast. Let's start with a little bit of background.

vitamin C, also known as escorbic acid, is an essential nutrient widely recognized for its antioxidant properties. What does that actually mean? Well, oxidation is a normal process in the body. It occurs as a result of day-to-day cellular activities involving normal metabolism, immune function, and a slew of other things. Having too many oxidized molecules hanging around promotes oxidative stress, a key driver of many chronic diseases. vitamin C can donate electrons to oxidized molecules to deoxidize them, officially known as reduction in chemical terms. Hence, the term antioxidant.

Even in small quantities, vitamin C can protect critical molecules in the body, such as proteins, lipids, carbohydrates, and nucleic acids, DNA and RNA, from oxidative damage. Vitamin C also plays a critical role as a co-factor. Co-factors are molecules that help enzymes involved in chemical reactions. This means that vitamin C supports a ton of physiological processes, including immune function, wound healing, fatty acid metabolism, neurotransmitter production, and blood vessel formation, as well as lots of other key processes and pathways.

Vitamin C's role in immune function in particular is crucial, but we'll talk about that in detail later. An interesting thing about vitamin C is that most animals can synthesize their own vitamin C, but humans can't. We have to get it from our body. our diets or from supplements. So let's talk a little bit about dietary sources of vitamin C. Most people probably automatically think of citrus fruits like oranges and lemons when it comes to vitamin C, but it's in a lot of fruits and vegetables, with the highest amounts found in guavas,

kiwis, and bell peppers. Unfortunately, cooking and exposure to oxygen can destroy 25% or more of the vitamin C in foods, so it's best to eat vitamin C rich foods raw and immediately after cutting or peeling. Worth a special mention is the fact that, generally speaking, meat is a very poor source of vitamin C. In fact, of more than 950 beef items listed in the USDA's food and nutrition database, only 21 items contain any vitamin C at all, and most contain tiny amounts that would be lost in cooking. Some organ meats, like beef spleen, lungs, and thymus, contain a little bit of vitamin C, but most people don't eat those kinds of vitamin C. But most people don't eat those cuts of meat. Eating an overly restrictive diet focused exclusively on meat could feasibly cause

vitamin C deficiency. Recommended intakes of vitamin C for healthy people. How much vitamin C do you actually need? Well, that depends on a lot of factors, such as age, sex, and life stage. For example, needs are fairly high in infancy. They decrease slightly durings childhood, and then they peak in early adulthood. Pregnancy increases a woman's vitamin C needs, but so does breastfeeding. That's because vitamin C is present in breast milk, where it acts as an antioxidant, which is pretty cool if you think about it. The recommended dietary allowance, or RDA, for healthy men, is 90 milligrams per day. For women, it's 75 milligrams per day. Taking really large doses of oral vitamin C can cause some GI issues, such as diarrhea. So at the other end of the recommendations

is the tolerable upper intake limit, 2,000 milligrams per day, the amount that experts believe reduces the risk of these GI problems. It's interesting, however, that there really isn't any scientific evidence that vitamin C administered in doses up to 10 grams per day in adults is toxic or detrimental to health. A person's overall health or lifestyle factors influences how much they need too. For example, if a person smokes or drinks alcohol, they'll have higher needs than someone who doesn't. That's because smoking increases oxidative stress, increasing antioxidant needs. alcohol consumption increases urinary vitamin C losses by nearly 50%, so higher intake might be needed to prevent deficiency.

A few medical conditions increase a person's needs, including inflammatory bowel diseases like Crohn's or ulcerative colitis. And kidney failure really takes a toll on vitamin C levels, especially if a person is undergoing dialysis. A study involving 22 patients with renal failure and their matched healthy controls found that a single dialysis session decreased the patient's plighton's pletions. plasma vitamin C levels to roughly half of their pre-diolysis levels. The idea behind the different RDAs is that research shows that consuming these amounts will maintain the optimal blood

concentration of approximately 50 micromoles per liter of blood, a concentration necessary to prevent oxidation of LDL cholesterol. The RDA also incorporates some data on levels needed for neutrophils. When neutrophils are activated in response to infection, they consume massive amounts of vitamin C because they release a ton of oxidants to kill foreign invaders. But these oxidants damage the neutrophils themselves, so they soak up vitamin C to prevent this damage. That probably seems a little abstract. You can't know what your blood concentration levels are without a blood test, but the symptoms of full-blown deficiency are not abstract at all. The classic manifestation of severe vitamin C deficiency is scurvy, a terrible condition characterized

by bleeding, swollen gums, poor wound healing, joint pain, and bruising. These early features of scurvy show up in as little as three months of vitamin C depletion, which is why sailors, who were often at sea for long periods without access to fresh foods and vegetables, often developed scurvy. As scurvy progresses, a person might experience shortness of breath, dry eyes, joint swelling, weakness, fatigue, and depression. Getting less than 10 milligrams of vitamin C daily is thought to cause scurvy. It's interesting that some disease states can induce scurvy-level vitamin C status. A population-based cross-sectional study of 149 patients admitted to a large teaching hospital

found that 60% of the patients had low vitamin C levels, and 19% were deficient with levels approaching those associated with scurby. But scurby is pretty rare these days, so there's a new school of thought that says the RDA should be increased, with less emphasis. on preventing scurvy and more emphasis on preventing chronic diseases. In fact, some scientists think there is enough evidence to support increasing the RDA for vitamin C to 200 milligrams per day for adults. This level of intake could elevate tissue levels potentially reducing the risk for chronic diseases such as heart disease, stroke, cancer, and metabolic dysfunction. Let's move on to vitamin C

absorption and transport. The absorption, distribution, metabolism, and excretion of vitamin C are complex and differ quite a bit from other low molecular weight compounds. Vitamin C is present in the body in two different forms, either its reduced state, escorbate, or its oxidized state, dehydroescorbic acid. Dehydroescorbic acid undergoes frequent intracellular recycling back to the reduced state. This cycle happens about four times for every vitamin C molecule. Oral vitamin C is absorbed in the small intestine, primarily via sodium-dependence, vitamin C transporters and to a lesser extent, glucose transporters. Absorption of the vitamin C via sodium-dependent vitamin C transporters is dose-dependent and subject to transporter saturation.

There are single nucleotide polymorphisms in genes that encode for the sodium-dependent vitamin C transporters, and these genetic variations affect vitamin C absorption. This brings me to an interesting side note. During the time when scurvy was rampant among sailors who all pretty much ate a similar diet, only about half of them came down with scurvy while the other half were unaffected, perhaps due to the genetic variation in the genes that encode for the transporters. For example, one polymorphism in the sodium-dependent vitamin C transporter results in a protein with 40 to 50% decreased ability to transport vitamin C into the cell. That could make a huge difference in a person's susceptibility to scurvy on a low vitamin C diet.

So back to transport and how vitamin C gets into the body's tissues. Dehydroescorbic acid competes with glucose for uptake via glucose transporters in the gut. That means its uptake might be impeded in a person with high blood glucose levels, like in diabetes. Fortunately, most tissues, including those in the gut, don't transport dehydroascorbic acid. Instead, with the exception of a blood, with the exception of blood, red blood cells, they use sodium-dependent vitamin C transporters to transport escorbate. Red blood cells transport dehydroscarbic acid only, and they generate their own escorbate via

recycling. After vitamin C is absorbed, it enters the plasma and then gets distributed throughout the body's tissues. The concentration in different tissues varies, with the lowest amounts found in muscle, heart, and kidneys, and the highest amounts found in the brain and adrenal glands. In a classic example of body triaging based on needs, the brain retains vitamin C during times of deficiency at the expense of other tissues. Vitamin C can be broken down in the liver into various intermediate molecules, and in the end, vitamin C and its metabolites accumulate in the kidneys and are excreted in urine. Urinary excretion is directly proportional to plasma concentrations. So that's how vitamin C gets into the body, but more importantly, how much gets it.

in other words, how bioavailable is it? Well, that depends. It turns out that the bioavailability of oral vitamin C is both frequency and dose dependent. For example, a person who gets roughly 200 milligrams per day from food or supplements will have plasma concentrations averaging around 70 micromoles per liter of blood. That's because vitamin C's bioavailability maxes out at about 200 milligrams when given as a single dose. 500 milligrams, the bioavailability decreases and excess vitamin C gets excreted in the urine. But that's not the end of the story. Even though bioavailability is diminished after 500 milligrams per day, plasma levels still increase after higher oral doses up to 3 grams, producing transient

peak plasma concentrations that are two to threefold higher than those with 200 milligrams of oral vitamin C. The plasma levels peak at around 220 micromoles per liter and return to baseline after 24 hours. It's important to note that multiple high doses of vitamin C supplements in the 2 to 3 gram range given 4 to 6 times per day maintain plasma levels 2 to 3 times higher throughout a 24 hour period. A few studies suggest that oral bioavailability of vitamin C can be increased when consumed in liposomal form, but only in doses higher than 5 grams. Liposomal vitamin C doses less than 5 grams achieve similar plasma vitamin C concentrations as non-liposomal vitamin C. Liposomes are lipid particles that can encapsulate water-soluble

substances like vitamin C. There aren't tons of studies along these lines, but a very small, single-blinded study with just two people showed that liposomal vitamin C, dramatically increased plasma levels in a dose-dependent manner. Whereas 20 grams of liposomal vitamin C increased peak plasma levels to approximately 320 micromoles per liter of blood, a 36 gram liposomal dose increased levels to 400 micromoles per liter. A slightly larger study with 20 people showed that a single 10-gram dose of liposomal vitamin C increased plasma levels to 300 micromoles, a concentration that is higher than the established peak concentration of 220 micromoles per liter. Not only that, the liposomal form took about an hour

longer to reach the maximum vitamin C blood concentration, and its half-life was two hours longer, compared to free vitamin C, indicating increased bioavailability. Not only that, the liposomal form took about an hour longer to reach maximum vitamin C blood, concentration and its half-life was two hours more compared to regular vitamin C, indicating increased bioavailability. On the other hand, intravenous vitamin C bypasses intestinal absorption, which means that it also bypasses the saturable transport mechanisms. That means that the bioavailability of intravenous vitamin C is a lot higher than oral vitamin C, potentially reaching blood concentrations that are 30 to 70 times higher than can be achieved orally. For example,

A clinical study involving 12 young adults found that plasma levels of vitamin C after taking a 1.25 gram dose of oral vitamin C reached about 135 micromoles per liter of blood, but they reached 885 micromoles per liter of blood with an intravenous administration of the same dose. Even when they increase the dose to 3 grams taken every 4 hours, peak blood concentrations with oral vitamin C only reached 220 micromoles per liter, but they reached 1,760 micromoles per liter for a single 3 gram intravenous dose. As I mentioned earlier, vitamin C is critical to immune function. Immune cells actively participate in eliminating pathogens such as bacteria or viruses from the body. Vitamin C is highly concentrated in immune cells, with neutrophils and

leukocytes having roughly 50 to 100 times higher vitamin C concentration. than plasma. One of the early stages of the body's immune response to viral or bacterial infection involves neutrophil infiltration into an affected tissue, where the cells engulf the pathogens and initiate their removal. Nutrophils generate large quantities of reactive auction species, but the high levels of vitamin C present in immune cells protect them from reactive oxygen species-induced DNA damage while also promoting Nutrophil reactive auction species production. Vitamin C also appears to boost the immune system by promoting the proliferation of T cells and preventing T cell death. T cells are lymphocytes. They play a major role in driving

immune response against pathogens, such as bacteria or viruses. Lots of in vitro studies in mouse and human cell lines have shown that growing T cells in culture with vitamin C decreases cell death and might even enhance T cell development. Another aspect of immune function that vitamin C might be important for is modulating cytokine levels. Cytokines are really important signaling molecules that are produced in response to inflammation and infection. Lots of immune cells secrete cytokines. In studies in which mice are vitamin C deficient, the mice have increased pro-inflammatory cytokines, but giving the mice vitamin C normalizes cytokine production. Let's talk about some specific ways in which vitamin C might affect immunity. As I already mentioned, the common cold

is probably the most extensively studied infection regarding the effects of vitamin C, with varied results. Much of this variation is due to the fact that a slew of factors such as age, dose, frequency, and duration of supplementation can affect the degree to which vitamin C can prevent or decrease episodes of the common cold. A med analysis of 23 clinical studies involving more than 6,000 participants sifted through these different factors and found that supplementation of at least two grams per cent, day of vitamin C during a cold had a greater benefit compared to a dose of one gram per day.

A sub-analysis of five of those studies showed that a higher dose of vitamin C supplementation was more effective against colds in children under 16 compared to adults. In adults, cold duration decreased 21% with 2 grams daily and decreased 6% with just 1 gram daily. But in children, cold duration decreased 26% with 2 grams daily and 17% with 1 gram daily. Another meta-analysis of nine studies compared the administration of vitamin C as a prophylactic measure. In other words, before you get sick versus a therapeutic measure. One group of participants took prophylactic doses of 1 to 3 grams every day over the course of several months, and then they took a therapeutic dose of up to 6 grams a day on the onset of cold symptoms.

symptoms. Another group only took the therapeutic dose. The prophylactic therapeutic combo reduced both the symptoms and the duration of a cold episode by about a half a day, but the therapeutic doses given only at the onset of symptoms had no effect. A larger meta-analysis of 29 trials involving more than 11,000 participants also looked into the use of vitamin C as a prophylactic. Doses ranged from 200 milligrams to 2 grams per. day for two weeks to six months. The relative risk of catching a cold when taken the prophylactic dose only decreased by 4%. Not much of an effect. But the 200 milligram dose used in some of these studies was a very low dose compared to the other studies. And it's possible that a higher

dose could have prevented more colds as demonstrated in the other studies. As I mentioned earlier, most people eating a varied diet have steady state plasma levels of vitamin C around 70 to 85 micromoles per liter. From pharmacokinetic studies, we know that 200 milligrams of oral vitamin C produces plasma levels of about 90 micromoles per liter, not much of an increase over baseline levels. A single 1.25 gram oral dose produced plasma vitamin C levels of 187 micromoles per liter, which is a bit more significant. With both amounts, plasma concentrations return to baseline values after 24 hours. A 3 gram oral vitamin C dose raised plasma levels to 220 micromoles per liter, a level much higher than steady state levels.

When that 3 gram dose was taken every 4 hours, the plasma concentration of 220 micromoles per liter was maintained throughout the 24-hour period. The pharmacokinetic studies are very important to keep in mind when trying to interpret inconsistent data, and even more important when designing a clinical trial. To get a measurable effect, you are going to have to significantly raise plasma vitamin C levels over their normal steady state levels. Two groups that seem to really benefit from prophylactic doses are endurance athletes and children. Six trials involving more than 600 marathon runners, skiers, and soldiers reported 50% fewer colds among those who took supplemental vitamin Cs.

suggesting that people who frequently participate in high-endurance exercise might be more responsive to supplemental vitamin C than others. And a comparison of 12 trials found a 13.5% reduction in cold duration among children compared to an 8% reduction in adults. Clearly, there are a lot of factors such as participants age as well as supplement dose and duration that can affect the outcome of vitamin supplementation on the incidence and duration of the common cold. These factors contribute to a lot of the inconsistencies in the findings among the various trials. A lot of these inconsistencies can be attributed to the shortcomings in the trial's designs, especially those utilizing low and or infrequent dosing schedules.

But despite the widespread inadequacies, meta-analyses broadly demonstrate in effect, particularly with higher doses. newer understandings of bioavailability might ultimately inform new trial designs that could still show a stronger effect, especially since plasma increases of low-dose vitamin C treatments are both transient and diminished, especially in trials that don't establish rigorous frequent dosing schedules. Ideal trial designs will assess blood kinetics based on dosing every few hours after symptom onset and utilize larger doses up to three grams. So let's shift from cold to conditions that affect the lower respiratory system, primarily the lungs.

The innate immune system of the lungs plays a really important role in the body's defense system because it protects the body from inhaled oxidants and pathogens. Vitamin C might help protect the lungs by boosting immune cell function and reducing oxidative stress. Some evidence shows that certain bacteria, like the ones that cause pneumonia, release large quantities of hydrogen peroxide into cells, inactivating inflammisomes. Inflamazomes are massive intracellular protein complexes that detect and respond to pathogens. Inactivating inflammisomes early on could weaken the immune response to lung infection. Vitamin C's role as an antioxidant could prevent hydrogen peroxide producing bacteria

from inactivating the immune response in the lungs. As it turns out, vitamin C might be protective against many respiratory diseases, the fifth leading cause of death among people living in the United States. One very large study looked at the relationship between blood vitamin C concentrations and incidence of respiratory disease in more than 19,000 people between the ages of 40 and 79 years without histories of respiratory diseases. The participants were categorized based on their baseline blood vitamin C levels, less than 41, between 42 and 54, between 54, between 54, and 66 and more than 66 micromoles per liter of blood. And then they were followed for about 16 and a half years. The people with the highest blood vitamin C concentrations were 15% less likely to develop

respiratory conditions and were 46% less likely to die of lung cancer compared to those with the lowest blood vitamin C levels. To be fair, it's important to note that the people who had the highest baseline vitamin C levels also had lower risk factors for development. developing respiratory diseases. They were generally younger and healthier. We're less likely to smoke, consumed less alcohol, were physically more active and had lower prevalence of other chronic illnesses than those with lower vitamin C levels. Let's look at mechanical ventilation, a process that's in the news a lot lately due to COVID-19. Mechanical ventilation is a strategy used to treat people experiencing respiratory failure. Vitamin C has proven to be effective at decreasing the amount of time

that patients are kept on mechanical ventilation. A meta-analysis of six studies found a significant difference in the effect of vitamin C on the duration of mechanical ventilation between patients on ventilation for more than 24 hours compared to those on ventilation for less than 24 hours. In three of those trials, two of which utilized intravenous vitamin C, patients were ventilated for more than 24 hours and given vitamin C spent 18% less time on mechanical ventilation compared to controls. But in trials where patients were on ventilators for less than 24 hours,

neither intravenous nor oral vitamin C had any effect on the duration of ventilation. So it seems that fewer than 24 hours on a ventilator is not enough time for vitamin C to exert its protective effects. Pneumonia is another big concern lately because it's a fairly common complication of viral infections. Although anybody can get pneumonia, it tends to be more severe in kids under the age of five and adults over the age of 65 years. evidence from observational studies suggests that vitamin C might be effective at preventing or treating pneumonia related to viral or bacterial lower respiratory infection,

especially in people with low baseline vitamin C levels. The evidence supporting vitamin C's effectiveness in reducing the risk of pneumonia in healthy men and women isn't as strong, though. Only five randomized controlled trials have explored whether the use of vitamin C can lower the incidence or severity of pneumonia. Three of the studies investigated the use of vitamin C. as a prophylactic treatment against pneumonia, and each found the incidence of pneumonia was 80% lower in people who took vitamin C compared to those who do not. But two of those studies involve people who were probably vitamin C deficient, a group of male students during World War II whose dietary vitamin C intake was very low, 10 to 15 milligrams

per day, and some military recruits in the former Soviet Union. A therapeutic trial involving 57 elderly patients diagnosed with, with either bronchitis or bronchone pneumonia, found that patients who took 200 milligrams of vitamin C per day showed improvements in respiratory function compared to the patients who were not administered vitamin C. It's important to note that these patients had baseline blood vitamin C levels that were roughly half the optimal concentrations of at least 50 micromoles per liter. Remember, 200 micrograms has been shown to raise plasma levels to 90 micromoles per liter, which might make a difference in someone with very low vitamin C levels, but perhaps not so much in someone that already

has a steady state level of 70 to 80 micromoles per liter. Taken together, these studies suggest that vitamin C might decrease the incidence of pneumonia in people who already have very low plasma levels of vitamin C. All right, let's look at asthma. Asma is a common long-term inflammatory disease of the airways of the lungs that affects a person's ability to breathe. Roughly one in 13 people living in the U.S. has asthma, which is quite a lot of people. Unfortunately, very few studies have looked at the role of vitamin C in reducing the symptoms and severity of asthma attacks, and the findings have been mixed. One study involved 41 asthma patients whose average age was 26 years old. The patients took one gram of vitamin C or a placebo daily for 14 weeks.

The patients who took vitamin C had fewer, less severe asthma attacks compared to the placebo group. But a separate study involved 300 asthma patients between the ages of 18 and 60 years who took one gram of vitamin C and 450 milligrams of magnesium chelate or a placebo daily for 16 weeks. Low blood magnesium levels have been implicated in the severity of asthma. At the end of the study, there was no evidence of beneficial effects on any outcome measure of asthma control. So obviously, more randomized placebo-controlled studies are needed to determine whether vitamin C might improve symptoms and reduce the severity of asthma attacks. These studies also need to determine if

outcomes of asthma are altered by different doses of vitamin C, age, demographics, or varying baseline levels of vitamin C. Some evidence suggests that vitamin C might be protective against lung cancer, the second most common form of cancer among men and women living in the United States. A meta-analysis of 14 studies, comprising more than 6,000 lung cancer cases, found that vitamin C was not only protective, but also showed a dose-dependent effect. For every 100 milligram increase in daily vitamin C intake among men, the risk of developing lung cancer decreased 7%. Let's shift gears and talk about exercise-induced bronchonstriction for a moment. It turns out that supplemental vitamin C might also mitigate some of the symptoms associated with exercise-induced bronchonstriction,

a problem that affects roughly one-tenth of the general population, and as a many, as half of some of the competitive athletes. Basically, it's a narrowing of the airways that occurs in response to intense exercise. Sports physiologists typically characterize it as 10% or greater decline in the exercise-induced forced expiratory volume, known as FEV-1, which is a measure of respiratory capacity. A meta-analysis of three placebo-controlled studies found that when men and women between the ages of 7 and 28 years, took between 0.5 and 2 grams of vitamin C immediately before exercise for two weeks, vitamin C reduced the FEV1 declined by more than 8%, indicating that vitamin C might help

alleviate respiratory problems caused by exercise. Which brings me to the topic of exercise in general. vitamin C might enhance exercise performance by reducing the potential negative consequences of excess reactive auction species, but there may be a flip side to that, which we will get to in a minute. Reactive auction species are highly reactive molecules produced not only during normal metabolic processes, but also during exercise, as a consequence of exercise-induced immune activation. Excessive exercise-induced reactive auction species can promote immune dysfunction. But the extent varies according to the duration and extent of exercise. For example, high-intensity exercise such as long-distance running, where you'd expect a lot of

reactive auction species production, is linked to an increased incidence of upper respiratory infection. The flip side of this is that reactive auction species might actually mediate beneficial training adaptations as a part of a biologically useful signaling cascade. That means that vitamin C could blunt the beneficial training adaptations that reactive auction species might induce, such as increased mitochondrial number and function, improved insulin sensitivity and glucose utilization, and enhanced immune function among others. Lots of studies have looked at the role that vitamin C supplementation has on exercise performance

and physiological adaptations with varying results. Supplemental doses ranging from 400-millimeter. to 3 grams per day, decreased markers of muscle damage, such as creatine kinase activity and myoglobin concentrations, and reduced muscle soreness after exercise. But some studies using lower doses between 200 milligrams and 1 gram per day suggests that vitamin C has no effect on physical adaptations to exercise. If we take that a step further and look at vitamin C taken in combination with other antioxidants such as vitamin E, it actually appears to blunt cellular, adaptations to exercise. For example, in a randomized controlled trial of 54 young men and women

who took either one gram of vitamin C with 235 milligrams of vitamin E or a placebo for 11 weeks, both groups saw similar improvement in VO2 max compared to their pre-supplementation levels. But markers of mitochondrial biogenesis decreased in those who took vitamin C and E and increased in the placebo group, suggesting that the supplementation of vitamin C and E together might attenuate some of the beneficial cellular adaptations associated with exercise. What's driving the variation in these findings? It's likely multiple confounding factors, such as the dose and duration of vitamin C supplementation, or whether vitamin C is taken alone or with other antioxidants like vitamin E. On the other hand, the studies participants' physical fitness and baseline

vitamin C levels could also contribute to the varying results. A separate study found that low vitamin C levels might be linked to poor physical performance and increase oxidative stress. The study involved 100 men who were screened for vitamin C baseline values in blood. The 10 men having the lowest levels, about 35 micromoles per liter, and the 10 men with the highest levels, about 78 micromoles per liter, were assigned to two groups. The 20 participants performed a aerobic exercise to exhaustion before and after 30 days of supplementation with either one gram of vitamin C or a lactose control. At the end of the study, the men with low baseline vitamin C levels had lower VO2 max levels

compared to the high vitamin C group. However, the men with the low baseline levels did show some improvement in that they had reduced biomarkers of oxidative stress. Let's shift gears a bit and talk about another benefit of exercise that might be affected by vitamin C, improved insulin sensitivity. Just a single bout of exercise rapidly improves the body's ability to take up and utilize glucose. Some studies show that when vitamin C is taken with other supplemental antioxidants, it might attenuate these beneficial effects. For example, a study involving 40 men, 20 untrained, and 20 pre-trained, found that 500 milligrams of vitamin C taken twice a day,

along with 400 IUs of vitamin E, reduced insulin sensitivity compared to a placebo. All the men in this study participated in an exercise training program of approximately one hour of cycling or running plus circuit training five days a week for four weeks, along with daily supplementation. The exercise improved the men's insulin sensitivity only in the absence of antioxidants. But another study in 21 physically active men between the ages of 18 and 40, years who took 500 milligrams of vitamin C and 400 I use of vitamin E or a placebo every day for 16 weeks showed that antioxidant supplementation had no effect on insulin sensitivity.

The differences in these findings of these two studies might be due to the dose and duration of vitamin C and vitamin E supplementation in relation to exercise. The first study looked at supplemental vitamin C and E taken at two separate occasions during the day. but the second study supplemented vitamin C and E at breakfast only, likely a few hours before exercise. Since the half-life of oral vitamin C is only a few hours, it's possible that sustaining vitamin C plasm levels by consuming multiple doses of vitamin C throughout the day can blunt exercise-mediated improvements in insulin sensitivity. It will be important to uncouple the effects of supplemental

vitamin C from vitamin E, since both trials included both anti-oxygen, it is unclear whether vitamin C alone would blunt exercise-induced insulin sensitivity. Taken together, the inconsistencies in the findings of all these studies looking at the effects of exercise and vitamin C might be attributable to differences in the conditions of vitamin C intake, such as the dose, duration, and timing, as well as the exercise protocol. Another important variable is the addition of supplemental antioxidants, such as vitamin E, at doses that are considerably higher, as in 17 times higher than the RDA. Furthermore, supplementation of vitamin C might affect exercise-induced oxidative stress

and training adaptations differently depending on an individual's baseline vitamin C levels. One of the things I alluded to before is how exercise influences immune function. Studies show that frequent, moderate to vigorous acute exercise sessions lasting about an hour can boost the body's immune system, but repeated high-intensity training or competition in endurance activities such as long-distance running can actually diminish it due to exercise-induced oxidative stress. In fact, quite a few epidemiological studies have linked endurance activities to a higher risk of upper respiratory infections. Some research has looked at the effectiveness of vitamin C alone or in combination with vitamin E as a means to increase immune cell function and

oxidative capacity to protect against exercise-induced immune dysfunction. And the findings weren't that impressive. Generally, they found that supplemental vitamin C doses of one to two grams per day for one to two weeks didn't cause any improvements in immune function before or after prolonged exercise. But the results among those participating in high endurance training were a little more promising, especially if vitamin C was given along with additional antioxidants such as vitamin E and beta carotene. As I mentioned before, a meta-analysis of six trials involving more than 600 marathon runners, skiers, and soldiers reported 50% fewer colds, suggesting that people who frequently participate in high-endurance exercise might be more responsive to supplemental vitamin C than others.

For example, a randomized controlled study in 20 athletes in their early 20s who participated in duathlon-like competitions found that antioxidant supplementation increased the antioxidant defenses of neutrophils. The athletes took either an antioxidant cocktail consisting of 250 milligrams of vitamin E and 15 milligrams of beta carotene or a placebo every day for 90 days. During the final 15 days of the study, the athletes took an additional supplement of 1 gram of vitamin C or a placebo. At the end of the study period, plasma antioxidant concentrations were considerably higher among the supplemented group than those of the placebo group. The activity of catalase, superoxide dismutase, glutathione peroxidease, and glutathione reductase in the

supplemented group's neutrophils increased, too, good indicators of enhanced neutrophil function. Several other studies in trained runners have shown that vitamin C doses ranging from 150 to 900 milligrams per day, in conjunction with vitamin E and beta carotene, enhanced neutrophil function, and reduced exercise-induced oxidative damage in lymphocytes. Again, there seems to be a fine line between exercise intensity, duration and frequency, vitamin C dose, and whether other antioxidants were taken. Let's move on and discuss vitamin C and fatty acid oxidation. Now this is something that I found really interesting. Vitamin C influences fatty acid oxidation, which is a mechanism to utilize fat as an energy source and is commonly referred to as fat burning.

Vitamin C levels are inversely correlated with body fat, particularly among people who are obese. Given that vitamin C is essential for the synthesis of carnitine, which plays an important role in the utilization of fatty acids as energy, it's possible that low vitamin C levels contribute to increased fat storage. A study in mice that were fed a high fat, high sugar diet, also known as a Western diet, with or without vitamin C found that vitamin C reduced weight gain in the mice, particularly in terms of fat mass compared to mice fed the Western diet alone. In addition, a mouse model of Werner syndrome, a genetic disorder characterized by premature aging,

demonstrated that vitamin C supplementation lengthened the average lifespan of the mice and corrected many of their age-related metabolic diseases. The supplemented mice also exhibited increased levels of PPAR. alpha, a protein that regulates fat metabolism by increasing uptake and utilization. But let's talk about some human data along these lines. A clinical study in 22 men and women between the ages of 18 and 38 years looked at this relationship between vitamin C status and fat oxidation during exercise. Fifteen of the people in the study had marginal vitamin C blood levels, less than 34 micromoles per liter, and seven had adequate vitamin C

levels, greater than 34 micrormoles per liter. As a part of the study, all participants completed a 60-minute treadmill walk at 50% of their VO2 max. Fat utilization during exercise was 25% lower among the people with marginal vitamin C status, suggesting that vitamin C affects fuel utilization during exercise. The authors of the study took it a step further, though. After four weeks of vitamin C depletion, they gave the participants either 500 milligrams of vitamin C or a placebo every day for four additional weeks. At the end of the eighth week, the average blood vitamin C levels in the supplemented group were about 42 micromoles per liter versus about 10 micromoles per liter in the depleted group. Not only that, but fatty acid utilization in the supplemented group was about four times greater

than in the vitamin C depleted group. These animal and human studies provide some pretty convincing evidence that vitamin C participates in fat metabolism, and having a higher vitamin C status may be necessary for effective fat utilization and weight management. Let's move on and discuss vitamin C in the brain. Vitamin C is found in high concentrations in the brain, especially in the hippocampus and frontal cortex regions, areas that are important for memory consolidation, learning, and aspects of executive function. In fact, the brain is kind of greedy. It retains vitamin C during times of deficiency at the expense of other tissues.

But that's important because evidence suggests that vitamin C might play roles in the brain throughout the lifespan from development all the way up through older age. For example, studies in newborn guinea pigs have demonstrated that prenatal and postnatal vitamin C deficiency stunted hippocampal development in newborn guinea pigs by 10 to 30 percent. studies in human fetuses and stillborn babies suggest an important role of vitamin C in brain development during gestation. For example, vitamin C levels were up to 11 times higher at 11 weeks gestation compared to adults, and full-term babies had at least three times higher vitamin C levels compared to adults. Vitamin C's antioxidant capacity might be beneficial in decreasing the risk

of neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington disease, and multiple sclerosis by reducing brain oxidative damage, a key driver of neurodegenerative disease. A 10-year-long study involving nearly 5,400 participants who were at least 55 years of age, looked at whether dietary intake of antioxidants was related to the risk of developing Alzheimer's disease. after a mean follow-up of six years, 146 of the participants had been diagnosed with Alzheimer's disease, and the average intake of vitamin C was approximately 122 milligrams per day. For every 54 milligram increase in vitamin C intake,

there was an 18% reduction in the risk of Alzheimer's disease. In smokers, the protective effect of vitamin C was even more robust, with a 35% decrease in Alzheimer's disease risk for every 54 milligram increase. Vitamin C is also important for the regulation of neurotransmitters, the formation of neurocircuits, and lots of key brain functions. I go into more detail about the role of vitamin C in the brain in my overview article that can be found at foundmyfitness.com. So far, most of the studies I've described have used oral vitamin C. Let's swim, which gears now and talk about intravenous vitamin C. For the past several decades, intravenous

vitamin C has been used as a treatment for many types of viral infections, such as shingles, cold source, chickenpox, mononucleosis, and a lot of others. It's interesting that although intravenous vitamin C is widely acclaimed as a successful treatment for patients with oral and genital herpes, there really aren't any clinical studies supporting these claims. However, there are multiple case studies and observational reports that suggest intravenous vitamin C might be useful in reducing pain in people who have chicken pox or shingles. As far as mononucleosis goes, a retrospective study found that patients with mono who were given intravenous vitamin C show decreased viral titers and replication, but their antibody levels decreased 42%, probably due to

the reduced viral replication. A really serious complication of viral infection, particularly in children, is myocarditis. Inflammation of the heart muscle. A really large meta-analysis found that intravenous vitamin C combined with conventional therapy is better than conventional therapy alone for the treatment of viral myocarditis in children. Myocarditis can be caused by direct infiltration of the virus, but can also be secondary to severe hypoxia and the cytokine storm mounted in response to systemic infection. There has been preliminary evidence suggesting that myocarditis may occur in some severe cases of COVID-19, but it remains to be determined whether intravenous vitamin C can help with this. However, what I really want to focus on here in

terms of how vitamin C is useful in infection is the evidence supporting its use in the treatment of sepsis. Sepsis is a life-threatening condition that can arise when the body responds to a bacterial or viral infection. It can cause severe injury to multiple tissues or organs. At least one recent paper has suggested that Sarge-Cove 2, the virus responsible for COVID-19, causes sepsis. People with sepsis often have low vitamin C levels, which might be predictive of increased risk for organ failure. Some evidence suggests intravenous vitamin C might be an effective treatment for sepsis. For example, experimental studies in mice have demonstrated that intravenous vitamin C lessens the pro-inflammatory state associated with sepsis and preserves organ function.

In clinical studies, intravenous vitamin C reduced the number of hospital deaths among patients with sepsis. One study involved more than 160 patients admitted to the ICU for treatment of sepsis-induced acute respiratory failure. The patients were randomized to receive either a placebo or intravenous vitamin C at 50 milligrams per kilogram of body weight every six hours. hours for 96 hours. What's interesting is that the study revealed no differences in the primary outcomes of organ failure, inflammation, or vascular injury. But 28 days after beginning of the study, nearly half of the patients in the placebo group died compared to less than 30% in the intravenous vitamin C treated group. Furthermore, patients in the vitamin C treated group had more

ventilator-free days were transferred out of the ICU at a higher rate and had seven more hospital-free days compared to the placebo group. A separate study treated 47 sepsis patients with six grams of intravenous vitamin C four times per day for four days along with hydrochortizone, a type of steroid medication, and thiamine, a type of B vitamin. A control group of 47 other sepsis patients received the standard of care. Roughly 40% of the patients in the control group died, but roughly 8% of the patients in the vitamin C treated group died. In addition, the treated group exhibited improved organ function compared to the control group. These studies suggest that intravenous vitamin C alone or in combination with other treatments like thymann decrease the risk of organ failure and death in patients diagnosed

with sepsis. Let's move on and talk about intravenous vitamin C, as an adjunctive treatment to chemotherapy. I mentioned Dr. Linus Pauling earlier. Pauling was a Nobel Prize winning chemist who found clinical evidence suggesting that high-dose intravenous administration of vitamin C is useful as a supportive treatment for cancer, as well as a method to reduce the side effects of chemotherapy.

He pretty much put vitamin C on the nutritional map. Although Pauling's studies were heavily criticized due to lack of proper controls and standardization, many clinical studies have said, suggested a beneficial use for intravenous vitamin C as adjunctive therapy for cancer, with many of the findings suggesting a trend in overall survival rate for patients administered intravenous vitamin C in conjunction with the standard therapy. Ongoing and future research will likely determine specific types and stages of cancer,

along with an appropriate chemotherapy regimen that would call for the use of intravenous vitamin C. That being said, intravenous vitamin C seems to improve cancer patients' quality of life. A study involving 39 patients diagnosed with terminal cancer who received 10 grams of intravenous vitamin C twice a week and four grams of oral vitamin C daily for a week found that patients reported improvements in physical, emotional, and cognitive status, as well as reduced fatigue, nausea, vomiting, pain, and appetite loss. another observational study of a 125 patients diagnosed with breast cancer, 53 of whom received 7.5 grams of intravenous vitamin C once per week in conjunction with their

standard chemotherapy and radiation therapies, noted improved quality of life compared to patients who only received chemotherapy and radiation. Although these studies are purely observational, other clinical studies have indicated that intravenous vitamin C, when taken with standard chemotherapies might improve the quality of life for patients. So again, more studies are needed along these lines. Let's change topics and talk about fertility and reproduction. So here's another interesting thing I learned about vitamin C. It appears to play a role in fertility. Infertility affects more than 180 million people worldwide. One of the contributors to male infertility is excess reactive auction species. Evidence suggests that vitamin C

decreases reactive oxygen species and increases fertility due to its antioxidant activity. A study in 13 infertile men between the ages of 25 and 35 years who took one gram of oral vitamin C twice today for two months found that compared to baseline measurements, the men's sperm count increased 58 percent and sperm motility increased 48 percent, indicating improved semen quality. Other studies showed that one gram of oral vitamin C increased sperm quality and men exposed to toxins such as lead or those found in cigarette smoke. Let's move on to cardiovascular health now. High blood pressure is a major risk factor for heart disease and stroke,

two leading causes of death among people living in the U.S. Nearly half of all adults living in the U.S. have high blood pressure, and only about one-fourth of those have their blood pressure under control. Large population-based studies have found that vitamin C might protect against high blood pressure. A meta-analysis of 29 randomized placebo-controlled clinical trials involving more than 1,400 participants demonstrated that patients with high blood pressure who took an average of 500 milligrams of oral vitamin C per day for about eight weeks showed significant decreases in blood pressure compared to those who took a placebo.

Recent research suggests that intravenous vitamin C can reduce blood pressure in patients diagnosed with pre-hypertension, which is having blood pressure between 120 over 80 and 139 over 89 over 89. A study involving 26 patients who received 15 to 100 grams of intravenous vitamin C over the course of 80 minutes measured blood pressure at baseline and every 10 minutes during treatment. They found that the infusion reduced blood pressure 10 to 15 points in the first 10 to 20 minutes, but blood pressure returned to baseline by 30 minutes. The authors of the studies suggested that this might have been due to the physiological effects of the infusion itself, a phenomenon known as benodialation.

However, by 75 minutes of infusion, intravenous vitamin C administered at doses above 30 grams, significantly reduced systolic blood pressure up to six points, and diastolic blood pressure up to approximately seven points when compared to blood pressure pre-infusion, likely due to the effects of vitamin C. While intravenous vitamin C shows promise in acutely reducing blood pressure, more randomized placebo-controlled studies are needed to determine the degree to which intravenous vitamin C is effective as well as the duration of its effects. Let's move on and talk about inflammation. We talk a lot about inflammation here at Found My Fitness. That's because it plays such an integral role in the pathogenesis of so many diseases. Inflammation is

Inflammation is a biological response triggered by the immune system in response to physical injury or infection. Vitamin C's immune boosting in antioxidant properties mediate the body's inflammatory response, reducing the symptoms or risk of various diseases. A randomized study of nearly 400 healthy adults who took one gram of vitamin C, 800 I use of vitamin E, or a placebo every day for two months, looked at whether antioxidants could lower. C-reactive protein, an inflammatory biomarker associated with cardiovascular disease risk. The vitamin C and E decrease C-reactive protein nearly 17% compared to pre-treatment measurements, but only in people who had elevated baseline levels of C-reactive protein. That's roughly the same amount that statins reduce C-reactive protein. Rumatoid arthritis is an autoimmune disorder characterized by widespread systemic inflammation.

Some studies have tested the effect of intravenous vitamin C in reducing inflammation and pain in patients with rheumatite arthritis due to its capacity to modulate the immune system and decrease oxidative stress. A study involving 11 female patients between the ages of 45 and 69 years who were diagnosed with rheumatoid arthritis and had been given intravenous vitamin C for varying durations, found that women's C-reactive protein levels decreased 44% compared to. levels before treatment. While more studies are needed to determine if decreasing C-reactive protein in patients with arthritis leads to improvements in joint and bone health, vitamin C might be useful

in decreasing some aspects of inflammation. So how does it work? Well, vitamin C uses a lot of mechanisms to promote health. First of all, it directly influences immune activity. Immune cells actively participate in eliminating pathogens such as bacteria or viruses from the body. As I mentioned earlier, vitamin C is highly concentrated in immune cells, with neutrophils and leukocytes having 50 to 100 times higher vitamin C concentrations than plasma. The role of vitamin C in neutrophils is to serve as a potent antioxidant. One of the early stages of the body's immune response to viral or bacterial infection involves neutrophil infiltration into an affected tissue, where the cells engulf the pathogens and initiate

their removal. Studies in animals and humans suggest that vitamin C plays an important role in facilitating neutrophil migration to sites of infection and overall neutrophil function. Nutrophils also generate large quantities of reactive auction species. As I mentioned before, this is important for neutrophil function, but it can damage the neutrophils in the process. The high levels of vitamin C present in immune cells promote the neutrophils reactive of auction species production, while also protecting them from damage. Aside from enhancing immune cell function, in vivo studies have shown that vitamin Codulate cytokine levels.

Cytokines are a class of protein secreted by many types of immune cells. They are important signaling molecules produced in response to inflammation and infection. In mouse models in which mice are vitamin C deficient and have increased pro-inflammatory cytokines, giving the mice vitamin C normalized. cytokine production. Vitamin C is also involved in the production of interferon in mice. Interferon is a type of cytokine that signals the body to initiate antiviral defenses. Vitamin C works through a variety of other mechanisms, such as blocking glucose uptake,

which is really important in terms of cancer, generating hydrogen peroxide and inhibiting viral replication. Most cancers rely primarily on glucose to generate energy through the process of glycolysis. Consequently, many types of cancers have increased glucose uptake. As I mentioned earlier, vitamin C is transported across cellular membranes by sodium-dependent vitamin C transporters and glucose transporters. The glucose transporters primarily import dehydroscorbic acid, deoxidized form of vitamin C, into cells. An in vitro study suggested that the import of dehydroescorbic acid into cancer cells can cause.

cause oxidative stress and decrease cancer cell viability. Some of the glucose transporters have a greater propensity to transport dehydroascorbic acid into cells over glucose. As a result, high concentrations of dehydroscorbic acid derived from vitamin C might inhibit glucose uptake into cancer cells and therefore hinder cancer cell fuel utilization needed for survival and growth. While vitamin C acts primarily as an antioxidant at physiological concentrations of approximately 50 micromoles per liter, pharmacologic doses of intravenous vitamin C greater than 1 gram generates hydrogen peroxide, a type of reactive oxygen species that can damage DNA, RNA, and proteins leading to tissue damage.

Multiple studies suggest that high-dose intravenous vitamin C can assist in cancer cell death primarily due to the formation of hydrogen peroxide. Some evidence suggests that vitamin C generates hydrogen peroxide by interacting with high levels of iron found in cancer cells. Cancer cells often have lower levels of enzymes involved in the detoxification of reactive oxygen species compared to healthy cells, potentially increasing oxidative stress in causing cancer cells to die. It's important to note that successive treatments with high dose intravenous vitamin C do not

increase pro-oxidative markers in healthy people, suggesting that normal cells aren't damaged by the burst of hydrogen peroxide produced by the intravenous vitamin C. Vitamin C also interferes with the replication of viral particles. One in vitro study showed that intravenous vitamin C infected cells that were incubated for four days with a 150 micrograms per milliliter of vitamin C decreased parameters of virus production such as reverse transcriptase activity by 99% and P24 antigen levels by 13% compared to untreated cells. Another in vitro study showed a dose-dependent effect of vitamin C to kill influenza viruses, with a vitamin C concentration of 2.5 milamoles per liter eliminating 90% of the virus present

and a concentration of 20 milamoles per liter fully blocking viral replication. A really interesting study using a vitamin C defecision. Mousinousant mouse model demonstrated that these mice had increased pro-inflammatory cytokines and a 10-to-15-fold increase in viral titers in their lungs during viral infection compared to normal mice. One week after the mice developed a viral infection, all of the vitamin C deficient mice had died, but all of the normal mice survived. When vitamin C deficient mice were supplemented with vitamin C prior to viral infection to achieve plasma levels of approximately 80, to 100 micromoles, similar to that of normal mice, there was no increase in viral tithers in

their lungs, and the production of antiviral cytokines increased. This study showed that supplementation with vitamin C prior to viral infection protected the formerly deficient mice from death. Let's talk safety. As I mentioned earlier, a tolerable upper intake of 2,000 milligrams of oral vitamin C per day has been established because vitamin C can sometimes cause GI problems such as diarrhea. For most people, however, vitamin C intakes at doses above the RDA for oral vitamin C are well tolerated and safe. But vitamin C supplementation is not a good idea in some medical conditions. For example, people who have hemachromatosis or whose iron levels are abnormally high should exercise caution when considering vitamin C supplementation due to its propensity to improve the absorption

of dietary iron. Intervenous vitamin C is well tolerated and has low toxicity. The most commonly reported side effects include mild to moderate nausea, headache, and dry mouth. Less common side effects include fatigue, hypertension, loss of appetite, and hyperglycemia. Some serious side effects have been reported with high dose intravenous vitamin C in patients. with cancer. In addition, people who have a deficiency in the enzyme, glucose-6 phosphate dehydrogenase, are at risk of hemolysis, the rupturing of red blood cells when given high doses of intravenous vitamin C. It's worth noting that the intravenous doses used in these studies were 40 grams or higher. Other case reports have indicated that when given at a dose between 1 to 10 grams, intravenous vitamin C can

reduce hemolysis. Therefore, it's possible that at lower doses, intravenous vitamin C is safe in people with glucose 6 phosphate dehydrogenase deficiency. Let's talk about kidney stone risk. A huge concern for many people is the perceived risk of developing kidney stones when taking high oral doses of vitamin C. Some studies have suggested that vitamin C intake is a risk factor for kidney stones due to the formation of oxalate, which is an end product of vitamin C. metabolism. The kidneys typically filter oxalate and excrete it in the urine, but when high amounts of oxalate are present, it can form crystal structures with calcium. These crystal structures can lead to the formation of solid masses that can promote the formation of kidney stones. A small number of case

reports indicate that a condition called oxalate nephropathy in which oxalate calcium crystals form in the kidney has been observed when patients with kidney impairment were given high doses of intravenous vitamin C. Two large prospective cohort studies involving tens of thousands of people found that high vitamin C intake increases the relative risk of kidney stones. But the findings are slightly misleading because they didn't report the actual incidence rate of kidney stones. The higher risk was only found after statistical manipulation of the data,

and the patients with higher vitamin C intake actually did not have more kidney stones. I'm going to go in a little statistical tangent because I find it very misleading that two studies found no association between vitamin C intake and kidney stone risk doing a univariate analysis, but then went on to do a multivariate analysis. Normally, multivariate analysis is great, but if you find no statistical significance on univariate analysis, there is no point in going to do multivariate analysis. When you do a multivariate analysis, you transition from actual patients

who experienced actual events to theoretical patients, who experienced theoretical events. Who cares if there is a theoretical risk of vitamin C and kidney stones when in reality, those with high vitamin C intake did not experience any more events of kidney stones

than those with lower vitamin C intake. These findings make me think that the body has a compensatory mechanism to prevent kidney stones when high amounts of vitamin C are consumed. The increased risk is theoretical when factoring out those compensatory factors. Okay, end of rant. Another prospective cohort study in more than 48,000 Swedish men found that the men's risk of developing kidney stones was 0.16% per year among men who did not supplement, but was 0.3% per year among those who did, which is a statistical difference with no clinical significance. In other words, a person in this study who supplemented with vitamin C can expect a kidney stone every 323 years, whereas a person who did not supplement

with vitamin C can expect a kidney stone every 613 years. Studies of high-dose intravenous vitamin C in cancer patients have not reported any impairments in kidney function. Taken together, these studies suggest that high-dose vitamin C might lead to kidney stones in patients with pre-existing kidney impairments, but vitamin C poses a relatively low risk of developing kidney stones in most healthy people. Woo! Let's round this up.

Vitamin C is widely recognized as a potent antioxidant. and a critical component of the immune system. It participates in a boatload of biological processes and pathways and affects multiple organ systems. Recommended intakes for vitamin C vary according to age, sex, and life stages of healthy people. But higher intakes, especially in quantities achieved with supplemental vitamin C, are associated with reduced risk of developing a vast array of acute and chronic diseases ranging in severity from the common cold to cancer, cardiovascular disease, disease and nerve degenerative disorders. On the other hand, low vitamin C intake and subsequent

deficiencies impair key biological processes and pose increased risk for certain conditions, such as decreased fat utilization during exercise and increased severity of Alzheimer's disease. Vitamin C might be especially beneficial for critically ill people, particularly those with viral infections who commonly have lower blood levels of vitamin C compared to healthy people. The effects of intravenous vitamin C differ considerably from those achieved with oral intake because of the huge concentrated increase in plasma levels that occurs with intravenous administration. As a result, intravenous vitamin C offers promise as a therapeutic strategy against certain types of cancer and infections that oral supplementation cannot achieve.

With some exceptions, both oral and intravenous vitamin C supplementation have been shown to be safe, well-tolerated and have low toxicity. The seemingly contradictory findings from much of the research on vitamin C appears to arise from differences in study design, populations, dose, and delivery modalities, as well as a host of other factors. Future studies based on consistent, equivocal study designs are necessary to elucidate the full potential of vitamin C in benefiting human health. That's it. Thank you so much for listening today. If you know someone who can benefit from this information, please share this podcast with them. To learn more about vitamin C and other topics, visit my website at foundmyfitness.com and look for the

topics drop down at the top of the homepage. In addition, we created a video with illustrated visuals to complement this podcast, which you can access on my website's episode page at foundmyfitness.com forward slash episodes. Here at Found My Fitness, we understand that getting accurate information is difficult. During a time with a lot of noise and misinformation online, our team wants to make sure that you're getting well-sighted, accurate, and trusted information. If you value what the team and I are doing, please consider becoming a premium member. When you become a Found My Fitness supporter, not only will you get additional member-exclusive

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test out there, such as 23 and me, then in all likelihood they have provided you with raw genetic data file that you can mine for additional goodies using our website. In particular, and especially notable in this context, there are genetic polymorphisms that affect vitamin C transport. As I mentioned in the podcast, you could run a totally free report with this SNIP and others like it by going to foundmyfitness.com forward slash genetics and selecting the basic report entitled Micronutrient Report. That's Micronutrient Report. Better still, if you like that free sample enough, you can get the upgraded experience by running the larger comprehensive report. The comprehensive report, which we charge for, grows by a double-digit percentage in terms

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