Should you increase your vitamin C intake? Genetics and vitamin C absorption

Vitamin C is often the first supplement most of us reach for when getting sick. Whether upping the OJ or going with a supplement, vitamin C is known for its ability to boost the immune system. It turns out, though, that vitamin C is important for more than just ‘cold and flu season’, and higher levels of vitamin C intake may protect against cardiovascular disease, gastric cancer, and neurodegenerative disorders.

Like most nutrients, our genes play a role in how vitamin C is absorbed, transported, and used by the body.  This can influence your risk for certain diseases, and it can make a difference in the minimum amount of vitamin C you need to consume each day.

Vitamin C:

Vitamin C (ascorbic acid) has a variety of functions in the body.  It is an antioxidant, as well as a co-factor in many important enzyme reactions, including the synthesis of collagen, carnitine, and some neurotransmitters. It is also important in regulating the absorption of iron and in immune function. [ref]

As an antioxidant, vitamin C donates an electron to do what is known in chemistry terms as ‘reducing an oxidant’. But vitamin C as an antioxidant isn’t quite as simple as the basic chemistry would imply.  When ascorbic acid donates an electron to a metal, such as copper or iron, it can lead to the production of superoxide and hydrogen peroxide, both of which are reactive oxygen species. Thus, in the body, vitamin C can act as an antioxidant or can cause the creation of reactive oxygen species, depending on the level and tissue concentration.[ref]

Within the body’s organs, the adrenals, brain, pituitary, spleen, eyes, and liver contain the highest levels of vitamin C. High levels of vitamin C are also found in neutrophils, monocytes, lymphocytes, and platelets – all are important in the immune response.[ref]

Vitamin C as a cofactor:

Ascorbate acts as an essential cofactor for a number of different enzymes.  Notably, vitamin C is a cofactor for the HIF (hypoxia-inducible factor), which controls a number of different genes and is important in tumor growth, heart disease, lung diseases, and diabetes. Additionally, vitamin C is a cofactor for several of the enzymes needed for collagen synthesis, and this becomes important when looking at the symptoms of deficiency.  [ref]

Absorbing and transporting vitamin C:

Most plants and animals make vitamin C and thus don’t need to get it through food. Humans, and some other primates, cannot make vitamin C and have to rely on food sources. (Yes – there are evolutionary theories on why we do not have a functioning gene for making vitamin C, but the main gist is that we don’t really need to make it since it is found in almost all plant foods. Plus, when infected with worms, they will make vitamin C for us in the intestines. eeww.)

The basic process for most vitamins and nutrients is that you eat food,  and then your body digests the food (chewing – then down the hatch to stomach, enzymes, into the intestines…). In the intestines, the nutrients – in this case, vitamin C – have to be moved from the interior of the intestines into the epithelial cells that make up the walls of the intestines.

Our bodies have vitamin C transporters that are involved in the absorption of ascorbate (vitamin C) in the intestines. When vitamin C is consumed – either through foods or through supplements – the transporters allow the absorption of vitamin C into the cells of the intestine wall and then into the bloodstream for transport throughout the body.

These vitamin C transporters are then needed for moving ascorbate from the bloodstream into the cells. Additionally, a glucose transporter (GLUT1) can transport the reduced form of vitamin C into cells, where it can be recycled back into the ascorbate form. [ref]

What happens when you don’t get enough vitamin C?

There are several major diseases associated with low vitamin C levels – with symptoms ranging from mild annoyances to, well, death from scurvy.

Scurvy is usually the first thing to come to mind with vitamin C. Made famous by sailors who went months at sea with no fresh fruits or vegetables, scurvy is caused by a vitamin C deficiency that lasts a month or more.  Symptoms of scurvy include fatigue, bleeding gums, easy bruising, poor wound healing, and bone pain. Vitamin C is needed in the synthesis of collagen, so the symptoms of scurvy are almost all related to defective collagen in the skin, blood vessels, and bones. [ref]

Vitamin C intake of less than 10 mg/day can lead to scurvy. This is rare to find in most modern countries. In the US, the average intake of vitamin C from food is around 100mg/day. [ref] Many people get additional vitamin C from multivitamins, supplements, and fortified foods.

Lower levels of vitamin C consumption are also associated with increased risk of several major diseases including cardiovascular disease, gout, and stomach cancer.

Studies show:

  • Higher intake of vitamin C is associated with a reduced risk of cardiovascular disease. Higher plasma vitamin C levels (whether due to genetics or due to higher fruit and vegetable intake) is associated with a reduced risk of both heart disease and overall mortality. [ref]
  • Reduced risk of stomach cancer is linked to higher vitamin C intake.[ref] Stomach cancer is now the third leading cause of cancer deaths worldwide.[ref] The link between vitamin C and gastric cancer may be due to the influence of vitamin C on gastric mucosa and on h. pylori replication.  H. pylori is the bacteria that can cause gastric cancer and ulcers. [ref]
  • Higher plasma vitamin C levels are linked to lower plasma urate levels and a lower risk of gout.[ref]
  • Vitamin C is important for glucose and lactate metabolism in the brain. This plays an essential role for vitamin C in neurodegenerative disorders and cognition. [ref][ref][ref]
  • Higher levels of vitamin C help to protect against pathogens such as HPV, the flu, and other viruses. Vitamin C is important for the production of interferon, which is the immune system’s first line of defense against viral pathogens. [ref][ref][ref][ref]
  • Vitamin C is important in wound healing, and higher levels of vitamin C may help with the repair of the cornea [ref]

What do your genes have to do with your vitamin C levels?

I mentioned above that there are specific transporters for vitamin C, coded for by a couple of genes (SLC23A1, SLC23A2).  The amount of vitamin C that you absorb from food varies according to genetic differences.  For example, when you and your friend eat an orange, your friend may absorb twice as much vitamin C as you do.

Understanding the different genetic variants that impact vitamin C levels can also be used to determine the effect of vitamin C on different diseases. When researchers discover that a certain variant causes low vitamin C and that same variant is linked to gastric cancer, it adds to the evidence that low vitamin C levels increase the risk of gastric cancer. [ref][ref]

SLC23A1 and SLC23A2 are the genes that code for the two vitamin C transporters. Variants in these genes are linked to altered risk of gastric cancer, cardiovascular disease, and more. The highest variation in these vitamin C transporters is found in African populations. This may be because there has traditionally been an abundance of vitamin C containing foods in the region and thus the genetic variants were not deleterious there. [ref]

Studies on vitamin C supplementation:

There have been numerous clinical trials and observational studies trying to determine the effect of vitamin C.

A meta-analysis of studies using IV vitamin C in ICU patients found that it decreased the length of stay in ICU by about 8%. Additionally, vitamin C reduces the length of time on a mechanical ventilator by 17%. The researchers commented that even though the 8% decrease in ICU time isn’t huge, the cost of vitamin C is dirt cheap and thus very cost-effective here. [ref]

Supplementing with vitamin C (oxaloacetate 100mg / ascorbic acid 150 mg) cut depression and anxiety rates by more than half for women suffering from PMS.  That is a pretty big impact from just taking some vitamin C. [ref]

A meta-analysis of a bunch of trials shows that vitamin C supplementation reduces the risk of cancer mortality by about 20%. [ref]

Studies on vitamin C for reducing the risk for the common cold show a variety of different results – depending on the study group and the amount of vitamin C taken.  One recent study in Korean army personnel found that 6g of vitamin C per day reduced the risk of colds by 80%. Note that the dose was 6 g (6000 mg) per day, so it may be that high doses of vitamin C are more effective for reducing colds. [ref]

There have been quite a few studies (dating back to 1986) showing that intravenous vitamin C reduces mortality in both sepsis and in ARDS (acute respiratory distress syndrome). The more recent trials show pretty dramatically that IV vitamin C reduces mortality in sepsis (e.g. 14% mortality rate for vit C vs 64% without).  [ref]

Vitamin C and Cancer:

This is a touchy subject for many people! The alternative medicine camp declared that high dose vitamin C can cure cancer — and there has been a big push back to censor people who say this. YouTube’s CEO has specifically mentioned taking down videos that discuss vitamin C for cancer.  I hate to even include research studies on this topic, for fear of being penalized in the Google algorithm…  but deliberately leaving out these studies would be a form of bias and censorship on my part.

So I’m going to explain some of the recent studies on using vitamin C as a therapy (often along with traditional chemo) for cancer patients. You can read the research and draw your own conclusions here. (Note – I’m not a doctor, nor am I advocating for a specific treatment here.)

A 2019 review article in the journal Nature Cancer explains that there are some anticancer properties of vitamin C that need to be further investigated with high-quality clinical trials. This review article explains that high doses of vitamin C given intravenously can be cytotoxic to some types of cancer cells. Important here is that there is no way to get vitamin C levels high enough to cause cancer cell death through oral doses, due to the saturation of the transporters in the intestines.

The Nature review article goes on to explain that in healthy cells, most vitamin C is transported in using the vitamin C transporters (SLC23A1, SLC23A2), but in cancer cells, the reduced form of vitamin C is brought into the cells at 10-20 times greater rate through the glucose transporters (GLUT1, GLUT3). This is due to low concentrations of the reduced form of vitamin C in cancer cells driving the uptake of more. Researchers think that this increased uptake of vitamin C along with iron in the cancer cell generates a lot of H2O2 (Hydrogen peroxide), which can kill the cancer cell.  [ref]

Important to note here is that IV vitamin C may work for specific types of cancer and for specific mutations in different cancers.  This isn’t a DIY thing – obviously!

Recent vitamin C  cancer studies:

  • In leukemia, vitamin C levels are low. Increasing vitamin C may only work for people with GLUT3 transporters (SLC2A3 gene) that work well.  [ref]
  • A recent (May 2020) study shows that vitamin C plus a fasting-mimicking diet may be effective in KRAS-mutant colon cancers. The fasting-mimicking diet downregulates certain genes, increasing the effectiveness of vitamin C reacting with iron to create oxidative stress that kills the cancer cell. [ref]
  • In thyroid cancer cells, blood glucose levels may be playing a role in how much vitamin C is brought into the cell. High levels of glucose don’t allow the GLUT1 and GLUT3 transporters to bring in the vitamin C. [ref]
  • Another recent study found that supplement vitamin C (oral) enhanced the effect of treatment (DNMTi-treatment) on blood cancers. [ref]

My two cents: If you have cancer and are discussing IV vitamin C with your doctor, consider the role that glucose levels play in whether vitamin C will be taken into the cancer cells via GLUT1. Talk with your oncologist about dietary options for lowering glucose (e.g. keto diet, diabetes drugs) and see if that would be helpful in your situation.

Testing Vitamin C levels:

There are various nutritional blood test panels that will measure vitamin C levels.  Generally, less than 0.2 mg/dl is considered deficient to the point of causing scurvy. [ref] But keep in mind that vitamin C levels fluctuate throughout the day, so it makes a big difference in your levels depending on the time of day when getting the testing done.


Genetic Variants:

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SLC23A1 and SLC23A2 are the genes that code for vitamin C transporters.  Variants of these genes affect the plasma levels of vitamin C.  All of these variants are very common; some are associated with higher plasma vitamin C concentrations and some with lower concentrations.

Check your genetic data for rs6133175 (23andMe v4; AncestryDNA):

  • G/G: 24% higher (on average) plasma vitamin C concentrations.[ref]
  • A/G: typical vitamin C levels
  • A/A: typical vitamin C levels

Members: Your genotype for rs6133175 is .

Check your genetic data for rs6053005 (23andMe v5 only)

  • T/T:  24% higher (on average) plasma vitamin C concentrations.[ref]
  • C/T: typical vitamin C levels
  • C/C: typical vitamin C levels

Members: Your genotype for rs6053005 is .

Check your genetic data for rs33972313 (23andMe v5 only)

  • T/T:  9% – 11% lower plasma vitamin C concentrations.[ref][ref][ref]
  • C/T: lower plasma vitamin C
  • C/C: typical

Members: Your genotype for rs33972313 is .

Check your genetic data for rs10063949 (23andMe v4, v5):

  • T/T: greater vitamin C transport, lower risk of Crohn’s [ref]
  • C/T: less vitamin C transport (most common genotype)
  • C/C: less vitamin C transport

Members: Your genotype for rs10063949 is .

Check your genetic data for rs12479919 (23andMe v4):

  • T/T: half the risk of gastric cancer[ref][ref]; higher levels of vitamin C.[ref]
  • C/T: typical risk of gastric cancer
  • C/C: typical

Members: Your genotype for rs12479919 is .

Check your genetic data for rs33972313 (23andMe v5):

  • T/T: decreased plasma vitamin C levels.[ref]
  • C/T: decreased plasma vitamin C
  • C/C: typical, reduced risk of heart disease compared to T/T [ref]

Members: Your genotype for rs33972313 is .

What about GLUT1?
SLC2A1 (also known as GLUT1) is the gene that codes for the enzyme that transports glucose across the cell wall.  This same enzyme also transports the oxidized form of vitamin c, dehydroascorbic acid, into cells where it is then reduced to ascorbic acid. [ref]  While there are studies linking GLUT1 polymorphisms to diabetes in some populations, I didn’t find any relating to vitamin C levels in the cell.


Lifehacks:

I hope you come away from this article with a realization that vitamin C is essential and needed for preventing various chronic health conditions (especially cardiovascular problems) as well as being important in the immune response. We are all different, though, in how much vitamin C we need each day.

How much do you need?

The US RDA for vitamin C is 60mg per day, which is just a little higher than what is needed to prevent scurvy (46mg/day). Many sources recommend getting more than the US RDA, and the studies on cardiovascular disease indicate that a higher intake is necessary for heart health.

At the high end of the recommendation scale, the Vitamin C Foundation recommends 3000 mg/day.[ref] A little more conservatively, the Linus Pauling Institute recommends 400mg/day.

All of those recommendations on intake are very general and don’t take into account your own personal genetic variants.  If you carry several of the variants linked to low vitamin C levels, you may want to increase your intake – and spread it out over the course of the day.

Vitamin C is a water-soluble vitamin and non-toxic, so excess vitamin C is eliminated and doesn’t build up.  You (and your bathroom) will know when you’ve had too much. The term ‘personal bowel tolerance’ applies here. Some people can take vast amounts of vitamin C orally without intestinal troubles, but for others, more than a couple of grams can cause, well… rumbling.

Eat your fruits and vegetables:

Excellent food sources of vitamin C include oranges, grapefruit, kiwi, strawberries, tomato, and red peppers.

Carnivore diet:

In general, meat is not a good source of vitamin C, unless you are regularly consuming the odd organ meats (spleen anyone?).  So if you are on a carnivore diet, you may want to either test your vitamin C level regularly – or just go ahead and supplement with ascorbic acid.

Supplements:

There are all kinds of vitamin C supplements available at your local grocery store – from the chewables to tablets to capsules to expensive liposomal forms.  Some animal studies show that vitamin C with flavonoids (quercetin, rutin) is better absorbed, but other studies show that some flavonoids inhibit vitamin C transporters. [ref]  Human studies don’t show a big difference between synthetic ascorbic acid and natural vitamin C.[ref][ref]

My recommendation here is to read the labels and avoid a bunch of junk in your supplements.

Personally, I go with just a bulk powdered ascorbic acid supplement, when I think to take it. I tend to increase my vitamin C intake in the winter for overall immune system support – and because fruits and veggies aren’t in season then.  Vitamin C powder (ascorbic acid) is really cheap and has no added ingredients. You can add a little to a smoothie or a drink – or put it in a capsule if it is too sour for you.

Research shows that at 500mg doses, saturation is reached for most people. Multiple doses per day may be more effective than one higher dose. [ref]

Topical formulas of vitamin C are available, mainly as beauty treatments, since vitamin C is needed for collagen synthesis. Studies show that it is best absorbed at a pH of 3.5 and at a concentration of 10-20%.[ref] It seems, though, that topical absorption limits the vitamin C to the top layers of the skin and it is not transported systemically. [ref]

Related Articles:

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Vitamin B12: Genes that impact your need for B12
There are several genes that can influence your absorption, transport, and need for vitamin B12. Some people need higher amounts of B12, and some people thrive on different forms of B12. Take a look at your genetic data to see if you should up your intake of B12. (Member’s article)

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.