A Year of Legends: Best of 2024 at Dr. Kara Fitzgerald
Dr. KF SPONSORED CONTENT
I am eternally grateful to our sponsors who, by blogging, podcasting, and advertising with us, enable me and my team to devote energy and time to writing, research, and education. All the companies who sponsor us are those I trust for myself, my patients, and my fellow practitioners. Please check out their websites! – DrKF
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 the major benefits of vitamin C 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?
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.
Antioxidant Function
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:
1. Collagen
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.
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:
- Fatigue
- 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.
2. L-Carnitine
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.
3. Norepinephrine
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.
Hyper-methylation can also be measured and can be used to detect cancer. A new blood test in development that screens for 20 different types of cancer uses and assay for hyper-methylated segments of cell-free DNA released from dying cancer cells is in fact showing very promising results (Source 8) with a specificity of 99.4% and a sensitivity and a sensitivity of 76% (for stage 2), 85% (stage 3) and 32% (for stage 1). The test, developed by GRAIL, Inc., uses next-generation sequencing technology to probe DNA for tiny chemical tags (methylation) that influence whether genes are active or inactive. When applied to nearly 3,600 blood samples – some from patients with cancer, some from people who had not been diagnosed with cancer at the time of the blood draw – the test successfully picked up a cancer signal from the cancer patient samples, and correctly identified the tissue from where the cancer began (the tissue of origin).
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)
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 which is dependent purely on slow vitamin C transporters called Sodium-Dependent Vitamin C Transporters Type 1 (SCVT-1)
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. Liposomes are thought to fuse with the cell membranes of the small intestinal cells responsible for nutrient absorption thus ensuring enhanced and direct absorption of the vitamin C they contain.
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 our liposomal vitamin C.
For Dr. KF’s readers and patients you can now take 20% off with the following code: DRKF20%
References
- 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/
- 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
- New blood test capable of detecting multiple types of cancer https://www.sciencedaily.com/releases/2019/09/190928082724.htm
8 Comments
Related posts
What about the high oxalates in ascorbic acid? How do we get extra Vitamin C support and protect from oxalate toxicity? Thanks.
When dealing oxalate restrictions, ideally I would recommend working with a Functional Medicine trained nutritionist who can help address the reactivity at its root and provide guidance to maximize nutrition intake.
DrKF FxMed received this as an email from Dr. Thomas Sult:
“Towards the end the author suggests that doses in the range of 2 to 3 g per day may be difficult to absorb and so one should use liposomal vitamin C. I am unaware of any evidence to support this. It is a rare individual that will have difficulty absorbing 1 to 2 or 3 g of vitamin C per day. If one is trying to achieve goat levels of vitamin C meaning 20 g per day that’s when people might start to get into G.I. distress in fact dose is above 10 g a day and in a few cases 5 grams all at once my cause issues.”
Tom Sult, MD
Author: JUST BE WELL (goo.gl/jUbWIX)
3rdOpinion.us
The source I used is the Linus Pauling institute section on the Bioavailability of Vitamin C.
Even though higher doses than 2-3 Grams at a time are tolerated as far as GI distress is concerned, the actual absorption is fractional as you see below. It probably has to do with the sodium-dependent vitamin C transporters (SVCT1) saturation past a certain dose of Vitamin C.
Bioavailability:
Depletion-repletion pharmacokinetic experiments demonstrated that plasma vitamin C concentration is tightly controlled by three primary mechanisms: intestinal absorption, tissue transport, and renal reabsorption (22). In response to increasing oral doses of vitamin C, plasma vitamin C concentration rises steeply at intakes between 30 and 100 mg/day. Plasma concentrations of ascorbate reach steady-state at concentrations between 60 and 80 micromoles/L (μmol/L). This is typically observed at doses between 200 to 400 mg/day in healthy young adults, with some degree of individual variation (23, 24).
One hundred percent absorption efficiency is observed when ingesting vitamin C at doses up to 200 mg at a time. Higher doses (>500 mg) result in fractionally less vitamin C being absorbed as the dose increases. Once plasma vitamin C concentrations reach saturation, additional vitamin C is largely excreted in the urine.
Liposomal Vitamin C does not depend on the SCVT-1 for absorption and has a more steady, prolonged absorption than plain Vitamin C. In this study https://www.ncbi.nlm.nih.gov/pubmed/27375360 you can see the two graphs comparing a dose of 4 grams of Vitamin C powder versus 4 grams of Vitamin C liposomal. The liposomal formulation achieves higher levels than plain vitamin C and it continues to be absorbed for a longer period of time than the plain vitamin C.
I don’t think the GI tolerance of maximal doses of plain Vitamin C has to do with its absorption (which continues, but is fractional), but more to do with the osmotic effect of the Vitamin C – which at high doses will cause diarrhea and “the flush”.
Caveat: Only under the direction of a functional doctor! Step 2. Only for individuals who passed the Functional Doctor test – The preferred way of doing 20,000mg of Vitamin C, to help prevent, is 2,000mg per hour or but not more in any given hour. One way to do this safely, would be take 2,000mg Vitaman C every hour for 3 hours, 1 hour off, Every hour 2,000mg Vitamin C for 3 hours, 1 hour off, 3 hours with every hour 2,000mg Vitamin C, 1 hour off or more off and then finish the last dose of 2,000mg before bed. Step 1. is to change your diet and make it more oxalate free, support those kidneys and slowly up your vitamin C intake. Step 2 only comes in later, and under the supervision of a true functional doctor. What breaking up your intake does, is allows your body to process it better. While you do this, you drink plenty of fresh, purified water. I would do this under the direction of a Vegan dietician, as they know best how to get all of the required nutrients. Attention to Omega 3 to Omega 6 balance will also be needed. This isn’t to say you need to go Vegan. Most dieticians are well trained in pro-farmers, any vegetables will do diet. That isn’t healthy. Salads need to be more than head lettuce with a tiny amount of cabbage, carrots and radish on a plate.
Caveat: If you aren’t eating Fresh Basil leaves on your food (1/2 TB per day helps to break up smaller kidney stones), and are not eating parsley, cilantro, watermelon, garlic, apples, cucumber, asparagus, ginger but instead eating red meat, raw broccoli and cauliflower, raw spinach, lots of french fries, potato chips and other high oxalate foods, then you might as well stick to the FDA of Vitamin C because your body most likely can’t handle it. Also, if you cook broccoli in water, but dump out the water, then you get less oxalates. This should be true for most vegetables high in oxalates. Regardless, I wouldn’t take any supplements, up vitamin C intake, detox, etc. without seeing a Functional Doctor first. They will run the right tests and lead you to do all of this correctly, according to your own specific body’s needs.
Why 20,000mg of Vitamin C? Well, one family had 3 members who did this, and 2 family members who refused. Those who refused contracted covid. Those who did this, did not get covid. BUT, this is not scientific. It was only 1 family who found this out. However, not one functional doctor who has taken higher doses of Vitamin C (some unknown amount greater than the FDA amount and at least 2,000mg per day) did not get Covid. Many doctors and nurses are getting covid, in the Traditional clinics.
What is covid really? A more powerful cold of sorts. Its a virus. This isn’t really going away anymore than the flu is going to go away. Vaccines haven’t really worked very well for the flu, I doubt they’d work very well for Covid.
Alternatives: Everything Organic, non-gmo. Vegetables juice smoothies, fruit smoothies – both with red bell peppers, raw garlic (minced), fresh ginger (1 inch, minced), Leafy greens (red and green lettuce -5th or 6th on the list of being the most nutrient dense vegetables in the world, according to the cdc, watercress – the most nutrient dense vegetable in the world, according to the cdc). Every little bit helps, plus those who eat better (aka not FDA eating) tend to be healthier and have less illnesses.
I agree with you 100%
I recently read a study which reported that although natural sources of vitamin C was anti-atherogenic, that supplemental ascorbic acid could be atherogenic, causing carotid atherosclerosis and plaque. In your opinion, was that study accurate, or biased?
Pat, forward that study (or the website link to me) I honestly DOUBT it…. DrKF