We began our series on Vitamin C in Part 1 with a brief overview of the history of vitamin C. Now we can move on to important new findings and what they mean to health. How does vitamin C affect the immune system? What about vitamin C and cancer? The common cold? What should the RDA be? What is the optimal intake? What else can it do? Let’s call on vitamin expert Professor Manfred Eggersdorfer for some answers.

Manfred Eggersdorfer, Ph.D. is a professor of healthy aging at the University Medical Center Groningen (UMCG) in the Netherlands and the senior vice president of DSM Nutritional Products, in Kaiseraugst, Switzerland. He studied chemistry at the Technical University Munich and earned his Ph.D. in organic chemistry in the field of synthesis and characterization of unusual amino acids. He completed his post-doc at Stanford University, California, working with Carl Djerassi on the isolation and characterization of sterols from marine origin as potential contraceptives. He joined Roche in Basel, Switzerland, in 1999 as head of research and development of vitamins and continued in this role after Roche was acquired by DSM in 2003.

Dr. Eggersdorfer holds the chair for Healthy Ageing at the University Medical Center Groningen and is responsible for Nutrition Science and Advocacy at DSM Nutritional Products. His scientific work focuses on the role of essential nutrients for health, vitality and well-being, especially on the impact of inadequate intake and status of micro-nutrients on long term health and healthy aging. He is active as an advisory board member at the Johns Hopkins Bloomberg School of Public Health, member of the Nutrition Council of Tufts University Friedman School of Nutrition Science & Policy, board member of the Gesellschaft für Angewandte Vitaminforschung e.V. and affiliate of various other organizations. He is the author of numerous publications in the fields of vitamins, innovation in nutritional ingredients and a scientific reviewer for a variety of journals.

Passwater: Professor Eggersdorfer, as I remember in the 1970s, the interest in vitamin C centered around its role in building proteins including the collagens, its role in normalizing cholesterol levels, its anti-viral action and its antioxidant properties. What do you see as vitamin C’s most prominent roles today?

Eggersdorfer:Right. In the 1950s, the textbooks taught us that vitamin C prevents scurvy and assists in collagen formation. In the 1960s and 1970s, vitamin C was found to be the body’s major water-soluble antioxidant. And in the 1980s, much more was discovered about the essential roles of vitamin C.

Figure 1. Vitamin C is relevant in all tissues and organs. Courtesy of Professor Eggersdorfer.

Today, research in the role of vitamin C experiences a renaissance in view of its many functions and benefits for human health. The most prominent role of vitamin C is its immune stimulating effect, which is important for our body’s defense against infections. Next to this it also acts as an inhibitor of histamine, a compound that is released during allergic reactions. As a powerful antioxidant, it can neutralize harmful free radicals. The reduction of oxidative stress has a benefit in reducing risk for cardiovascular disease (CVD).

Health authorities also have started to recognize the inverse relationship between vitamin C intake and various forms of cancer, and issued guidelines to increase vitamin C intake via the diet and/or supplements. In this context, Dr. Mark Levine, one of the world experts in vitamin C, called for a re-evaluation of vitamin C as cancer therapy, especially intravenous vitamin C. Next to these prominent applications, vitamin C is required for the synthesis of collagen, the intercellular ‘cement’ substance which gives structure to muscles, vascular tissues, bones, tendons and ligaments. Due to these functions vitamin C, especially in combination with zinc, is important for the healing of wounds. Vitamin C also contributes to the health and stability of teeth and gums, preventing hemorrhage. It also improves the absorption of iron from the diet, and is needed for the metabolism of bile acids, which may have implications for blood cholesterol levels and gallstones. In addition, vitamin C plays an important role in the synthesis of several peptide hormones and neurotransmitters and carnitine.

Finally, vitamin C is also a crucial factor in the eye’s ability to deal with oxidative stress, and can delay the progression of advanced age-related macular degeneration (AMD) and vision-loss in combination with other antioxidant vitamins and zinc. So, in summary, vitamin C has a good number of important roles in health for humans.

Passwater:More specifically, what organs and systems do vitamin C affect?

Eggersdorfer:Vitamin C is relevant in all tissues and cells. The total body content of vitamin C ranges from 300 mg (less is associated with scurvy) to maximal about 2 g. High levels of vitamin C are maintained in cells and tissues, like in muscles, in the liver, in the lungs, in the kidneys and are highest in leukocytes (white blood cells), eyes, adrenal glands, pituitary gland, and the brain. Relatively low levels of vitamin C are found in extracellular fluids, such as plasma, red blood cells and saliva. Some medical conditions and drugs can reduce the absorption of vitamin C and/or increase the amount needed by the body. Figure 1 gives some typical levels of vitamin C in various tissues.

Passwater:I think both of us believe that there is scientific support for a higher RDA for vitamin C, but even in terms of the existing RDA, is vitamin C deficiency a problem?

Eggersdorfer:Right. A good number of studies and papers indicate that a higher intake of vitamin C compared to current recommendations provides many benefits. Experts in the field advocate for an RDA increase to 200 mg per person a day. Chinese health authorities have already taken this into account and have given two recommendations: 100 mg to avoid deficiency and 200 mg to reduce risks for non-communicable diseases.

Found in many fruits and vegetables, vitamin C is a delicate nutrient that is destroyed by heat. Consequently, in the modern Western diet where most people’s meals consist of processed foods, little vitamin C remains for absorption. The challenge of little vitamin C in the processed, modern diet is aggravated by the fact that the many individuals with blood sugar issues, such as hypoglycemia, require more vitamin C as this condition interferes with its metabolism by the body. In addition, alcohol consumption and common drugs, such as aspirin and the birth control pill, may reduce vitamin C levels in the body.

Although severe vitamin C deficiency is now relatively rare, the prevalence of milder or marginal deficiency is quite high. The European Nutrition and Health Survey reports mean vitamin C intakes ranging from 62 mg in women in the UK to 153 mg in German men.

However, despite the comparatively high mean intake in Germany, half the adult population has vitamin C intake below the currently recommended 100 mg per day. Using the cut-off of 60 mg/day and 50 mg/day for men and women, respectively, proportions of 8% to 40% of adults were reported to have inadequate intakes in a range of European countries. Similar rates of inadequate intakes relative to recommendations are reported from the US and Canada. (Please see figure 2.)

Passwater:What is recent research showing regarding vitamin C and health benefits?

Eggersdorfer:There is good evidence from recent research that regular use of vitamin C supplements shortens the duration and severity of the common cold. The common cold is a viral infectious disease of the upper respiratory tract. Colds can lead to the upper respiratory system becoming less resistant to bacterial infection, resulting in issues such as middle ear infection, pneumonia, bronchitis, or strep throat. There are currently no medicines available

Figure 2. Vitamin C deficiency is common in the Western World. Courtesy of Professor Eggersdorfer.

that will prevent or cure the common cold. However, in a recent Cochrane meta-analysis it was shown that vitamin C reduces the incidence, duration and severity of the common cold when ≥ 200 mg/day is taken daily when exposed to severe physical stress and/or cold.

Vitamin C is also thought to play an important role in the prevention of non-communicable diseases such as cardiovascular disease (CVD) and cancer. One difficulty is that randomized controlled trials are not necessarily suitable for detecting such a relationship between a nutrient and a disease. The link between inadequate vitamin C intake and non-communicable disease is best documented for CVD; this is well summarized in a detailed review by Dr. Balz Frei in 2012 (Crit Rev Food Sci Nutr. 2012;52(9):815-29. doi: 10.1080/10408398.2011.649149) and Dr. Melisa Moser in 2016 (Int. J. Mol. Sci. 2016, 17(8), 1328; doi:10.3390/ijms17081328). Given that atherosclerosis is an inflammatory disease, it seems likely that vitamin C plays an important role in protecting against it: Vitamin C depletion is thought to increase the susceptibility of LDL cholesterol to oxidation, a risk factor for CVD. However, it is now equally recognized that reactive oxygen species formed by the inflammatory response in an existing atherosclerotic lesion may reduce vitamin C antioxidant levels. A recent review of epidemiologic studies supports the finding that endothelial function and lipid profiles, especially in subjects with low plasma levels, are improved by vitamin C. This is in line with large prospective studies that have shown an inverse relationship between plasma, vitamin C status and the risk of CVD. Also, Langlois and colleagues showed a relationship between vitamin C concentration and the severity of atherosclerosis and inflammation in peripheral artery disease patients. Moreover, there is evidence from a meta-analysis of randomized controlled trials that vitamin C supplementation has a beneficial effect on blood pressure. (Please see figure 3 on next page.)

Passwater:The research on vitamin C and its ability to reduce infection is both interesting and important. Please discuss this with us.

Eggersdorfer:Vitamin C plays an essential role in immune function, which is impaired by insufficient supply and re-established through supplementation. It exerts its effect via the promotion of T-cell maturation by modulating the regulation of gene expression as a cofactor. For the circulating immune cells, the importance of vitamin C is highlighted by the preferential uptake and active transport by the vitamin C transporter located in the cell membranes, resulting in vitamin C concentrations 20 to 60 times higher than in the surrounding plasma. It is assumed that the high vitamin C concentration protects neutrophils from the reactive oxygen species (ROS), which kill pathogens such as bacteria and viruses.

Figure 3. Large prospective studies that have shown an inverse relationship between plasma vitamin C status and the risk of CVD. Courtesy of Professor Eggersdorfer.

Furthermore, vitamin C improves the immune function by influencing chemotaxis and chemokinesis of neutrophil leukocytes. These findings are supported by the observation that the vitamin C level is affected in people with infections, chronic diseases, and higher oxidative stress, as they lead to higher metabolic losses: e.g., during common cold. (Please see figures 4 and 5.)

Passwater:Colds are viral infections. What about the research on vitamin C and the common cold? Was Dr. Linus Pauling right?

Eggersdorfer:Indeed, given its importance for the immune system, improved vitamin C status can be expected to translate into clinical endpoints when faced with infections. There is good evidence that regular intake of vitamin C shortens the duration and severity of the common cold.

Figure 4. Vitamin C keeps neutrophils fit to protect the body from infection. Courtesy of Professor Eggersdorfer.

A Japanese study shows that the risk of getting three or more colds in a five-year period was decreased by 66% by daily intake of a 500 mg vitamin C supplement (Tomotaka Sobue et al., European Journal of Clinical Nutrition 60(1):9-17 February 2006 DOI: 10.1038/sj.ejcn.1602261). A recent Cochrane meta-analysis confirms that vitamin C reduces the incidence, duration and severity of the common cold when ≥ 200 mg/day is taken daily. (Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD000980. DOI: 10.1002/14651858.CD000980.pub4) This review investigated the effect of vitamin C intake on the common cold in adults and children. Vitamin C supplementation of ≥200 mg significantly reduced the duration of common cold symptoms in children. The effect was a reduction by ~14% and in adults, it was reduced by nearly 8%. On average, episodes of common colds last around 10 days and children tend to have 3 to 5 per year, while for adults it is 1 to 2. Consequently, it can be estimated that an adequate supply with vitamin C can reduce the days spent being ill by 4 to 6 and 1 to 2 for children and adults, respectively. In addition, the meta-analysis reported a reduction in the severity of the common cold thanks to supplementation with vitamin C. The incidence of common cold types of symptoms was reduced in participants under heavy physical or cold stress. (Please see figure 6.)

Passwater:Another contention by Dr. Pauling was that vitamin C could help prevent some cancers. What is new in this line of research?

Figure 5. Vitamin C promotes the mobility of neutrophils.
Courtesy of Professor Eggersdorfer.

Eggersdorfer:Numerous studies suggest that vitamin C plays a role in disease prevention. The role of vitamin C in cancer prevention has been studied extensively. Some prospective cohort studies and case-control studies show correlations between vitamin C serum level and incidence for cancer. In addition, it has been shown that high dose intravenous vitamin C applications in cancer patients improve quality of life, including physical, mental and emotional functions. And cancer patients might be at increased risk of vitamin C inadequacy so a higher intake is recommended. The Linus Pauling Institute has recently organized a full-day symposium with experts from all over the world to discuss the current evidence of vitamin C in cancer prevention and treatment to stimulate more research and applications in this promising field.

Prospective cohort studies and case-control studies show inverse correlations between vitamin C serum level and incidence for cancer. The higher the level of vitamin C in the blood, the lower the risk of cancer. In addition, it has been shown that high-dose intravenous vitamin C applications in cancer patients is prolonging life and improving the quality of life. This will be a topic of a future Vitamin Connection column.

Figure 6. Vitamin C reduces the duration, incidence and severity of colds.
Courtesy of Professor Eggersdorfer.

Passwater:Very interesting. Let’s discuss this more fully in a couple of future columns. The research with vitamin C and the brain is gaining interest. What is the latest here?

Eggersdorfer:There is emerging evidence that maintaining healthy vitamin C levels might offer some protection against age-related cognitive decline and Alzheimer’s disease. This is not surprising, in the light of the mounting evidence for the role of CVD and oxidative stress in the development of Alzheimer’s disease. The role and impact of vitamin C and brain development during pregnancy and over the life cycle requires more research and human studies. However, learning that infants with low levels of vitamin C have a lower number of neurons may open new and important applications for vitamin C in the future. So, in summary I am convinced that — after more than 100 years in vitamin research — we can still expect new insights and findings to the benefit of individuals and the society.

Passwater:Vitamin C is still thought of as being the anti-scurvy vitamin as if that was its only role in health. Higher levels of vitamin C over the present RDA levels offer additional health benefits. Let’s discuss more optimal nutritional levels of vitamin C in the next column and then supra nutritional (medicinal) levels in the following column.WF

For part 1 of this series please follow this link: http://bit.ly/2AlyweI