Science of Vitamin C: Benefits Beyond the Common Cold

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)