Vitamin C: Crucial or Controversial

We all know that Vitamin C is important for our health. This is why it’s one of the most popular nutritional supplements around the world. We learned in school about the connection between Vitamin C and scurvy, a disease that sailors used to get from lack of Vitamin C on long voyages. Now, we know that Vitamin C does a lot more than just prevent scurvy. It’s believed to boost our immune systems, protect us from diseases like cancer, and even help prevent damage to our cells.

Especially during the Covid-19 pandemic, people are looking for ways to stay healthy and protect themselves. That’s why there’s been a 70% increase in Vitamin C sales worldwide!

In this review, we’ll talk about all the current research on Vitamin C. We’ll cover its health benefits, where to find it in food, and how our diets can affect our Vitamin C levels. Plus, we’ll explore the debate over whether taking supplements is effective and whether it’s better to take ascorbic acid or a Vitamin C complex.

Lost gene

Did you know that we actually lost the ability to make Vitamin C in our bodies about 61 million years ago? Most animals and plants have a special gene that helps them make Vitamin C in their liver, but for some reason our ancestors lost that gene. Evolution led to us inheriting this missing gene.

Our ancestors still managed to survive without being able to make their own Vitamin C because they got enough of it from their diets. While we’re often told that fruits and vegetables are the best sources of Vitamin C, did you know that meat and organ foods also have good amounts of it? These animal foods provided enough Vitamin C for our ancestors, who lived in environments with very limited access to plant foods. ^(1,2)

Vitamin C and scurvy

Back in the 16th to 18th century, scurvy was a huge problem for sailors. It’s estimated that about 2 million sailors died from scurvy during that time. This is a disease that happens when we don’t get enough Vitamin C, which is important for the production of collagen. When we don’t have enough collagen, our connective tissue breaks down, leading to gum disease, tooth loss, fragile bones, poor wound healing, bruising, and bleeding.

At that time, people didn’t know about Vitamin C, but they figured out that rations of dehydrated meat and ship biscuits were causing malnutrition.They discovered that providing sailors with daily citrus juice or fermented cabbage helped eliminate this terrible condition.³

Now, we know that an intake of less than 10 mg/day of Vitamin C can lead to scurvy. That’s why Vitamin C is also called ascorbic acid, which means “anti-scurvy.” But aside from preventing scurvy, Vitamin C has many other benefits for our health.

Vitamins are a group of organic compounds, found in minute amounts in natural foods that are essential to our survival. They provide co-factors needed for normal metabolism and catalysts for biochemical reactions that maintain the function of our cells.

The many roles of vitamin C

Vitamin C is a powerhouse nutrient that plays many important roles in keeping our bodies healthy. One of its most important functions is its role in the production of collagen, which is a crucial component of our skin, bones, and connective tissue. But that’s not all – vitamin C also helps with the production of neurotransmitters like dopamine and norepinephrine, which are important for mood regulation and cognitive function.

Another vital function of vitamin C is its ability to act as an antioxidant. Free radicals and reactive oxygen species (ROS) are molecules that can damage cells and lead to chronic diseases such as cancer, heart disease, and Alzheimer’s. Vitamin C works to neutralise these harmful molecules and protect our cells from damage.

But the benefits of vitamin C don’t stop there. It also supports our immune system, helping us to fight off infections and illnesses. It can improve iron absorption, which is important for preventing anaemia. And studies have shown that it may even reduce the risk of certain types of cancer.

It’s clear that vitamin C is an essential nutrient that plays many roles in keeping our bodies healthy. By making sure we get enough of it in our diets, we can reap the many benefits it has to offer.

• Co-factor support for hydroxylation enzyme reactions
  • Hydroxylation of collagen and lysine
    • Repair and maintenance of connective tissue, skin, and blood vessels
  • Aids in the production of neurotransmitters
    • Dopamine and serotonin
  • Helps to regulates adrenal gland hormone production                                 
    • Epinephrine, cortisol
  • Critical for cellular energy production and fatty acid oxidation
    • Carnitine synthesis
• Assists nitric oxide enzyme activity
• Increases cholesterol secretion through bile acid production
• Helps with
  • Liver detoxification
  • Reducing gluten triggered inflammation
  • Reducing heavy metal accumulation
• Regulates immune response
  • Infections
  • Viruses
  • Bacteria
• Protects cells from oxidative damage
  • Protects from and destroys cancer cells
• Supports progesterone production, reducing estrogen dominance
• Aids in iron and copper absorption, transport, and recycling

Tissue requirements for vitamin C

Although vitamin C isn’t stored in the body, it does accumulate in tissues, where it can be 5-100 times higher than blood levels. The table below shows the concentrations in different tissues and fluids.

Vitamin C is preferentially accumulated in the pituitary gland followed by the adrenal glands and eyes, highlighting its importance in the function of these organs.

How much can we use from our food and supplements?

The absorption, transport, and recycling of vitamin C involves several transporters and complex mechanisms. Ultimately, the concentration in our blood and tissues is tightly controlled by how much can be:⁴

• Absorbed from the intestines: Blood levels reach a steady state at intakes between 200-400 mg per day. Once the plasma is saturated, any additional intake is excreted in the urine.

• Transported into the tissues: There are different types of transporters that help get vitamin C into tissues. Once tissue levels are saturated no more can be taken up.

• Reabsorption by the kidneys: When our vitamin C intake is low, our kidneys can reabsorb vitamin C, to help maintain plasma and tissue stores. Once these levels are saturated, the kidneys will excrete excess vitamin C in the urine.

The body is self-regulating in the amount of vitamin C it can absorb into the blood and tissues. Once these needs are fulfilled, excess will be eliminated in the urine.

Vitamin C Controversies

There is ongoing debate over the optimal intake of vitamin C for good health and whether supplementation is necessary.⁵ While there is solid evidence supporting the role of vitamin C obtained from food in maintaining optimal levels in the blood and tissues, there is controversy over the use of high doses of vitamin C supplementation. Many proponents advocate that more is better and high doses will confer additional benefits, despite evidence that excess is simply excreted in the urine. There is also debate over vitamin C requirements in the context of differing lifestyles and ways of eating^.6

The Ascorbic Acid versus Complex C Debate

Ascorbic acid is the chemical name for vitamin C, and it is used to identify vitamin C activity in the body and in food. Ascorbic acid is the form of vitamin C used in supplemental and intravenous vitamin C, and it is typically manufactured in a laboratory from GMO corn. It is also commonly added back into fruit juices and other foods to increase their vitamin C content.

On the other hand, complex C, which is found in fruits and vegetables, is a group of compounds surrounded by an ascorbic acid shell. Nature has designed this protective layer because these compounds are fragile and easily damaged by oxidation. As a result, consuming vitamin C through whole foods can offer the benefits of complex C in addition to ascorbic acid.

Dr. Royal Lee was a prominent figure in the field of nutrition and is often regarded as one of the greatest nutritionists of the 20th century.⁷ He was a strong advocate for whole food supplementation and believed that the best way to obtain nutrients was through natural, whole food sources. He is quoted as saying:

“In nature a vitamin is never a single chemical. Rather it is a group of interdependent compounds that form a nutrient complex, so intricate that only a living cell can create it”

Dr. Lee believed that vitamins need all their cofactors to function properly, and he used the analogy of a watch to explain this concept. Just as a watch needs all its different components to keep time accurately, a vitamin needs all its interdependent compounds to form a nutrient complex, which only a living cell can create. Therefore, taking a single component from a vitamin complex and calling it a vitamin is not enough to ensure proper function. Instead, he advocated for the use of whole food supplements that contained a complex of interdependent nutrients in their natural form.

What’s inside a vitamin C complex?

The compounds found inside a vitamin C complex are well recognised as contributing to health. Some researchers believe that these are important co-factors for ascorbic acid to fulfill its functions. They suggest that long-term use of ascorbic acid only supplements will deplete the body of these other vital nutritional factors and eventually lead to deficiencies and poor health.

Tyrosinase is a multi-copper enzyme that plays a critical role in the transport and bioavailability of iron. It also plays a role in the

• Oxidative burst in white blood cells that destroy engulfed pathogens

• Production of steroid hormones in the adrenal cortex (epinephrine and norepinephrine)

• Production of the neurotransmitter, dopamine

• Regulation of our antioxidant system

• Production of melanin in our skin

Copper is vital for many physiological functions in the body. High levels of ascorbic acid supplementation may induce a copper deficiency by competing with copper absorption in intestine.

Bioflavonoids and P factors surround the tyrosinase. I mentioned the effects of scurvy and how this was treated with citric juice. When ascorbic acid was discovered, it was believed that this was responsible for making the collagen to provide structure and integrity to skin, bone, and connective tissue.

More recent laboratory investigations have led to the recognition that bioflavonoids such as rutin, and P factors that are found inside the vitamin C complex molecule are also important in this process.

Vitamin K and J -factors (choline) increase the oxygen carrying capacity of the blood and are involved in many physiological processes including metabolic function, fat transport, and neurotransmitter synthesis.

Does Supplementing Improve Health?

There is no doubt that adequate vitamin C levels are essential for health. The research shows that optimal long-term levels support a health immune system and the data shows that any intake that saturates your plasma, will maintain optimal levels. However, before supplementing with ascorbic acid, there are important questions to ask.

• Is your normal diet maintaining blood and tissue concentrations? If so, will supplementation provide further benefit?

• Will supplementation help in deficiency states? What’s causing the deficiency.

• How much supplementation is required, what’s the best form and correct dose?

• Are there benefits to supplementation in the presence of illness or chronic disease?

• Will excess supplementation cause harm?

While there is copious research on the relationship between vitamin C and ascorbic acid, falling into two categories, clinical studies, and prospective/correlational studies. When considering studies, it’s important that they measure plasma concentrations rather than rely on food questionnaires and dietary intake records. There are many reasons why food intakes are not reliable. These include

• Poor reporting

• Losses during food handling and cooking

• Differences between plant and animal-based sources

• The effect of the overall diet and health on the absorption, transport and recycling system

• Total body vitamin and mineral status

While ascorbic acid is a functional component of the vitamin C complex, it only comprises 5-8 percent of the compounds. Ascorbic acid is the marker used to identify vitamin C activity and its presence in a food source.

Clinical studies

Overall, these studies showed an inverse relationship between plasma concentrations of vitamin C and overall mortality.

Cancer is a disease of concern and plasma vitamin C was inversely related to cancer mortality in men, but not in females.

In one study, unexpectedly, females with higher levels of plasma ascorbic acid were associated with an increased risk of cancer. In gastric cancer and hospice patients, low plasma concentrations were associated with greater risk and shorter survival. However, none of these prove causation – that lower vitamin C causes disease. At best they show an association. An alternative explanation may be that plasma levels decrease in the presence of chronic diseases.

Intervention studies

In these, vitamin C supplementation was provided. There are a lot of these types of studies. This summary only considers random controlled trials (RCT’s) and meta-analysis.

• Mortality: A Cochrane review that found that supplementation of antioxidants including vitamin C had no effect.

• Common cold: High dose vitamin C supplementation has been cited as reducing the symptoms and preventing the occurrence of colds and other vital infections. A Cochrane review found there was no reduction in the occurrence of colds. However, there was a modest reduction in symptoms. It may be beneficial to take a short-term dose of vitamin C when you get a cold^.8

• Cardiovascular disease: The studies show mixed results for CVD, with some showing no effect, while others found vitamin C to be beneficial.

Although a meta-analysis of showed a decrease in systolic blood pressure (3.8 mmHg), this wasn’t considered meaningful.

Vitamin C supplements and cancer

Understanding whether supplemental vitamin C, (often administered intravenously (IV)), is an effective treatment for cancer is an important area for research that could potentially improve the quality of life, or save lives, if found beneficial.^9,10,11,12

The theory behind IV administration13 is this will bypass the tightly regulated, absorption, transport and recycling of vitamin C allowing plasma levels to increase dramatically. It is surmised from test tube studies that high levels of ascorbic acid, become pro-oxidants by increasing the formation of hydrogen peroxide that is toxic to cancer cells.

At present there is only one RCT that assessed the effects IV vitamin C therapy in cancer patients. This indicated a reduction of chemotherapy induced side effects in ovarian patients. Unfortunately, no significant effects in terms of survival were found. There are other trials, including some phase I-II clinical trials that showed some transient benefits in a few patients. Again, no long-term improvements in survival were found.¹⁴

If you have cancer, it’s quite likely you will want to investigate anything that may help. There are some case reports describing benefits of IV vitamin C. This link is to a lecture by Otago University Professor Margreet Vissers is worth a watch and it may be worthwhile contacting her. https://youtu.be/Kh7k7fx0Y1U

I would also recommend looking at the work of Paleomedicina who specialises in helping cancer patients worldwide. They take a metabolic approach, with considerable success. https://www.paleomedicina.com/en/#rolunk

Do you know your vitamin C status?

We have long been taught that supplementing with water-soluble vitamins is safe because the excess will be excreted. This seems a complete waste of time and money to me. There are many lifestyle factors that will affect your plasma and tissue levels of vitamin C. We do know from the studies that lower levels are associated with increased mortality.

There are many factors that reduce your ability to absorb vitamin C. These include the usual suspects such as smoking, high alcohol consumption, caffeine consumption, exposure to environment toxins, low dietary intake, and poor overall nutrient status.¹⁵

Diets high in carbohydrates¹⁶, particularly processed foods from grains, cereals and seed oils increase your need for vitamin C. Glucose containing foods affect the transportation of vitamin C from the small intestine to the blood and from the blood to the tissues. For many tissues, ascorbic acid is oxidized to dehydroascorbic acid and is transported into the cells via glucose transporters (GLUT1 and 3). DHA will compete with glucose to get into the cell.

• In ascorbic acid recycling, ascorbic acid is oxidised to dehydroascorbic acid (DHA).

• DHA is then transported into the cell moving with its concentration gradient using GLUT1 or 3 receptors.

• Once inside the cell, DHA is converted back to ascorbic acid.

• As a result, the cell is able to accumulate high levels of ascorbic acid.

If you’re consuming a diet that leaves you struggling to control your blood sugars, it’s going to be a lot more difficult getting adequate vitamin C. This is particularly relevant to your brain cells as they can only take up the DHA form.18 It won’t matter if you take a supplement, the absorption and transport system are the same.^19,20

Different types of vitamin C supplements

Whole-food vitamin C complex

Whole food vitamin C should be derived from plants and shouldn’t contain ascorbic acid on the label. Many of the health benefits associated with vitamin C, come from synergistic interactions of the other compounds found inside the complex. 3rd party validation should be available from the company to verify their claims and the vitamin C content.

Synthetic ascorbic acid

Ascorbic acid was discovered in 1912, isolated in 1928 and synthesised in 1933. Most synthetic ascorbic acid is produced in China from genetically modified corn and processed with chemicals such as acetone

Mineral ascorbates

These are often called buffered vitamin C. The ascorbic acid is bound to a mineral (sodium, potassium, magnesium) to make them less acidic and easier to absorb for those who experience upset stomachs from pure ascorbic acid.

Ascorbic acid with bioflavonoids

These are an attempt to add back in some of the additional compounds found in whole-food vitamin C. These are often marketed as natural. However, to qualify as natural it only has to include 10% of the plant-derived ingredients. The other 90% can be synthetic.

Liposomal vitamin C

Synthetic ascorbic acid or a mineral ascorbate is mixed with a vegetable oil. The idea is the fat in the oil helps to improve absorption. I found one study that claimed liposomal C was 1.77 times better absorbed than other forms of ascorbic acid.²¹

Dosages and bioavailability

The RDA for women is 75 mg/day and 90 mg/day for men. The upper limit of tolerance has been set at 2,000 mg. This may be sufficient to prevent deficiency, but whether these doses will achieve optimal levels hasn’t been confirmed.^22,23,24

When reviewing the literature including plasma concentrations following intake, it appears that doses between 200-400 mg/day will achieve this.

You will find most supplement recommendations are significantly higher than this, many advocating 1-2 grams/day, some going as high as 5-10 grams/day.

The adverse effects of consuming high doses include digestive stress such as cramps, nausea, and diarrhoea. Some people may be vulnerable to iron overload, copper deficiency and kidney stones.^25,26,27

The ability to absorb vitamin C is >80% at intakes between 15-100 mg/day. The higher the intake, the lower the absorption rate. At 1.2 grams/day or more this is less than 50%.28

Summary

While it is important to maintain optimal vitamin C levels for good health, research has not supported the idea that supplementing beyond what is required to achieve optimal plasma and tissue levels provides additional benefits. In fact, excessive supplementation can even be harmful in some cases. It is important to consider individual factors, such as diet, lifestyle, and overall nutrient status, before supplementing with vitamin C.

References:

• 1. https://www.sciencedirect.com/science/article/abs/pii/S0309174006002701
• 2. Voegtlin V.L. The Stone Age Diet. Vantage Press, New York, 1975
• 3. https://www.usni.org/magazines/naval-history-magazine/2021/february/finding-cure-scurvy
• 4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579624/
• 5. https://ivcjournal.com/whole-food-vitamins/
• 6. Yang J., Liu J., Parry J. Vitamin C: Daily Requirements, Dietary Sources and Adverse Effects. In: Handbook of Vitamin C Research. Eds:
• Kucharski H., Zajac J. Nova Science Publishers, Inc., 2009
• 7. https://www.drroyallee.com/what-is-a-vitamin/
• 8. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000980.pub4/full
• 9. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029794
• 10. http://link.springer.com/article/10.1007%2Fs00280-013- 2179-9
• 11. http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876- 10-189
• 12. http://www.ncbi.nlm.nih.gov/pubmed/16570523
• 13. http://ict.sagepub.com/content/13/4/280.long
• 14. http://www.nejm.org/doi/full/10.1056/NEJM197909273011303
• 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959991/
• 16. http://jn.nutrition.org/content/130/1/63.long
• 17. http://onlinelibrary.wiley.com/doi/10.1016/S0014- 5793(02)03167-8/epdf
• 18. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC508490/pdf/1002842.pdf
• 19. http://ajcn.nutrition.org/content/90/5/1252.long
• 20. http://link.springer.com/article/10.1186%2F1475-2891-6-41
• 21. https://www.tandfonline.com/doi/abs/10.1080/08982104.2020.1820521?journalCode=ilpr20
• 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783921/
• 23. https://www.ncbi.nlm.nih.gov/books/NBK225480/
• 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835439/
• 25. https://academic.oup.com/ajcn/article/82/2/488/4863023
• 26. https://pubmed.ncbi.nlm.nih.gov/10218143/
• 27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192488/
• 28. https://www.karger.com/Article/Fulltext/434757#ref26