What do you think Vitamin C is for?
How much Vitamin C is enough and how much is too much?
What does Vitamin C actually do?
Most people that I ask these questions will say something like this…
“Vitamin C is for your immune system to treat or prevent colds and flus”
“take as much as possible” or “I take until my gut goes funny” or “1 or 2 grams every day or every couple of hours when sick”
“Vitamin C fixes /prevents scurvy”
Vitamin C is the greatest hoax played out in plain sight in the history of modern medicine. Vitamin C is possibly the most extensively studied vitamin, nutraceutical, complementary / natural medicine in history. We have more scientific data on vitamin C than any other ingredient. The science is solid and the data is of excellent quality and the conclusions in the white paper journal articles are real. In this case; the hoax is actually propagated by the victims of the hoax. It is a crazy situation where a lie or a hypothesis can get all the way around the world before the truth gets its pants on. It is the general public with old, wrong information, assumptions and marketing one liners and “naturopathic” rules and anecdotal reports that are insisting on using vitamin C at the wrong dose for the wrong reason. In this case the hoax is not created and propagated by “the man” or “big pharma” they are just supplying the demand.
No one needs to hide info or create fraudulent science because the general public is driving the vitamin C market and innovation. They want more! Because more is better! Right? Wrong. And in the case of vitamin C the real challenge is keeping the levels at the optimal level; too little or too much is bad for you. And furthermore Vitamin C needs other nutrients and cofactors (vitamins A, E, D, zinc, and bioflavonoids) in correct balance for it to function at its optimal level.
The Vitamin C story
Scurvy was discovered. Vitamin c deficiency was found to be the cause of scurvy. The term ascorbic acid is derived from anti-scorbutic, meaning anti-scurvy compound. Vitamin C deficiency was linked to low intake due to poor food choices, poor farming practices and food processing.
The need for vitamin C in the diet of humans is the result of an inborn error in carbohydrate metabolism. Most animals can synthesize ascorbic acid from glucose; humans, other primates and guinea pigs lack the enzyme required to make it.
Vitamins have always been consumed with the belief that they are essential and can only do good things with very little or no toxicities even at supraphysiological doses. The “more is better” philosophy is encouraged and side effects are dismissed.
Interestingly with so much research on vitamin C over so many years showing negligible effects from supplementation at doses beyond what is necessary to correct deficiencies the standard doses used by the general population far exceed what the science says we need. Furthermore research shows that vitamin C supplementation greater than 100-250mg per day for disease prevention at doses as little as 500mg daily can contribute negligible and in some cases negative results for cardiovascular disease, cancer, ageing, and all-cause mortality.
Even with all of these new discoveries in the public domain high dose supplements of various forms of vitamin C are readily purchased over the counter and with encouragement or prescription from healthcare professionals and consumed by the general public and with the assumption that it is without risk and free of side effects means that the negative effects are usually dismissed or attributed to something else.
So what does Vitamin C do?
All known and postulated actions of vitamin C are accounted for by a single chemical property: ascorbic acid is an electron donor and thus a reducing agent. The most well characterized actions are those as an enzyme cofactor, including those in which it is an actual co-substrate.
Physiological functions of vitamin C (L-ascorbic acid) include:
- Participation in hydroxylation reactions: collagen production, tyrosine, noradrenalin and serotonin, as well as L-Carnitine, steroid hormones of the adrenal glands and bile acids.
- Collagen production function is to facilitate the hydroxylation of proline and lysine residues in collagen, allowing proper intracellular folding of pro-collagen for export and deposition as mature collagen. Common symptoms of scurvy include wound dehiscence, poor wound healing and loosening of teeth, all pointing to defects in connective tissue. Collagen provides connective tissue with structural strength.
- Ascorbic acid and stress – it has been well known since 1920’s that the adrenal gland has high levels and highly active uptake of vitamin C. Previously it was believed that vitamin c was necessary for cortisol production but that has been disproven. Suggestions that vitamin C can be an anti-stress compound and correct adrenal exhaustion or adrenal fatigue oare also misleading. In the adrenal gland vitamin C works in both the chromaffin cell system of the adrenal medulla and adrenal cortex. Dopamine b-hydroxylase, found in neurosecretory vesicles and in adrenal chromaffin granules in the adrenal medulla is necessary for the synthesis of norepinephrine from dopamine in the nervous system and in the adrenal glands. Vitamin C also stimulates catecholamine release via NO-induced mechanism. During stress vitamin c helps to modulate the hepatic and adrenal CYP450 in particular CYP45011B that regulates aldosterone production and release for regulating sodium levels. Of course the antioxidant effects of vitamin C are protective to cell structures during increased physical and mental demand.
- Ascorbate has also been shown to assist in the hydroxylation of hypoxia-inducible factor 1α (HIF-1α). HIF-1α is a transcription factor responsible for the cellular response to low oxygen conditions through activation of genes controlling diverse cellular pathways including glycolysis, iron transport, angiogenesis and cell survival.
- As a reducer, it participates in biosynthesis of tetrahydrofolic acid (activated form of folic acid), hyaluronic acid (for collagen, joint and cartilage) and prostaglandins (inflammation and circulation)
- It also modulates the body’s immunity by stimulating the production of immunoglobulins and interferons
- Antioxidant Vitamin C is easily and reversibly oxidized into dehydro- L-ascorbic acid, creating a redox system which allows it to act as an antioxidant. It deactivates multiple ROS. It also regenerates vitamin E used up during similar processes. Thus, vitamin C plays an important role in eliminating oxidative stress which, in combination with its water solubility, makes it the main antioxidant of extracellular fluids.
- Pro-oxidant ascorbate can reduce metals such as copper and iron, leading to formation of superoxide and hydrogen peroxide, and subsequent generation of reactive oxidant species.
- Vitamin C also takes part in detoxification of xenobiotics contributing to the production of ROS
- Peptidylglycine a-amidating monooxygenase, found in secretory vesicles is required to amidate many peptide hormones to make them biologically active. These include many hypothalamic and gastrointestinal hormones such as gastrin, cholecystokinin, calcitonin, vasopressin and oxytocin;
- L-Carnitine synthesis – Trimethyllysine hydroxylase and c-butyrobetaine hydroxylases are required for carnitine synthesis from the essential amino acids lysine and methionine. The enzyme requires iron, alpha-ketoglutarate and a reductant, of which ascorbate is the most optimal.
- 4-Hydroxyphenylpyruvate dioxygenase is required for the catabolism of tyrosine. Ascorbate deficiency leads to impaired tyrosine catabolism and increased plasma concentrations of tyrosine.
- Elements of the antioxidant system, which are needed for the integrity of immune cells because they are subject to a high burden of reactive oxygen species (ROS)
- The hydroxylation of tryptophan in serotonin biosynthesis;
- The synthesis of catecholamines;
- Detoxification of numerous substances in the liver by stimulating the synthesis of cytochrome P450,
- A role in iron transfer from the iron transporting protein transferrin to the iron storage protein ferritin, promotion of intestinal iron absorption by reducing nearly non-absorbable Fe3+ to more easily absorbable Fe2+ and by inhibiting the production of insoluble iron-tannin and iron-phytate complexes,
- Ascorbate is proposed as a neuromodulator of glutamatergic, dopaminergic, cholinergic and GABAergic transmission and related behaviors.
Antioxidant or pro-oxidant?
Chemically, vitamin C is an electron donor, or reducing agent, and electrons from ascorbate account for all of its known physiological effects.
Vitamin C is called an antioxidant because electrons from vitamin C can reduce oxidized species, or oxidants. However, the same electrons from ascorbate can reduce metals such as copper and iron, leading to formation of superoxide and hydrogen peroxide, and subsequent generation of reactive oxidant species. Thus, under some circumstances ascorbate, is a pro-oxidant.
How much should I use?
The effect of a single oral dose of vitamin C on the intracellular ascorbate concentration of immunocompetent cells, like monocytes and neutrophils, is characterized by a sigmoidal response curve (Fig. 2). In adults, a vitamin C intake of approximately 100 mg/d results in complete intracellular saturation.
How much is too much?
Vitamin C is practically nontoxic, however, its large doses (500 mg/d or more) can cause alimentary tract disturbances (nausea, pyrosis and diarrhea), enhanced urination with a feeling of burning, and also erythrocyte hemolysis during glucose-6-phosphate dehydrogenase (G-6-PD) and vitamin B12 deficiency. To put this in perspective most people aim for 1000mg per dose with 2000 to 6000mg per day being a common dose. 500mg per day is a relatively low dose for vitamin C supplements.
By inducing severe urine acidification, such doses impair the excretion of weak acids and bases, which may result in the precipitation of cystinate and urate depositions in the urinary tract, leading to the formation of renal calculi. Vitamin C doses > 1g/d elevate blood and urinary oxalic acid concentrations to a degree increasing the risk of calculi formation from calcium oxalate. Thus, such large doses should not be administered in chronic renal failure, cystinuria, predisposition to gout, urate and oxalate calculosis. Therapeutically applied vitamin C increases blood sodium concentration and decreases potassium concentration which can lead to deficiency of the latter. Also, it negatively impacts on some drugs taken, causing vitamin B12 destruction (therefore, the two vitamins should not be administered in combination), and augments amphetamine derivative and tricyclic antidepressant drug elimination by inhibiting their reabsorption in renal tubules. Due to its chemical incompatibility, vitamin C should not be administered with drugs which have oxidizing properties. By acidifying the urine, it can lead to the crystallization of urine excreted p-aminosalicylic acid and sulphonamides. The use of high-dose vitamin C yields false results in body fluid analyses performed with the use of methods based on redox reactions, e.g. determinations of bilirubin, glucose, or creatinine concentrations, and LDH or AspAT activity.
High doses of vitamin C hamper copper absorption and inhibit copper-containing ceruloplasmin and superoxide dismutase (Cu,Zn-SOD) activities . In contrast, they enhance iron absorption to the harmful degree in individuals with its excessive intestinal absorption, and also in those with increased blood iron concentration, and with hemochromatosis, sideroblastic anemia or thalassemia (where the symptoms exacerbate. The excess unbound iron accumulates in the tissues and skin, irritates gastrointestinal mucosa, causes intoxication, and contributes to the prooxidant effects of vitamin C.
There is so much… I will keep updating as I work through the data, but here are some revioews. And just for fun check out the Cochrane database. Cochrane reviews are the gold standard for scientific validity; do a search for ascorbic acid and see what you find.
Oral Dis. 2016 Sep;22(6):463-93. doi: 10.1111/odi.12446. Epub 2016 Apr 14. Vitamin C: the known and the unknown and Goldilocks. Padayatty SJ1, Levine M1.
Strohle A, et al. Micronutrients at the Interface between Inflammation and Infection – ascorbic acid and calciferol. Part 1: General Overview with a focus on Ascorbic Acid. Inflammation and Allergy – Drug Targets, 2011, 10,54-63
Int J Occup Med Environ Health. 2012 Jun;25(2):105-21. doi: 10.2478/S13382-012-0022-x. Epub 2012 Apr 19. Adverse effects of antioxidative vitamins. Rutkowski M1, Grzegorczyk K.