Vitamin C Deficiency and Vitamin C Insufficiency: A Review for the Hair Loss Practitioner.

Vitamin C Insuficiency and Deficiency

Vitamin C deficiency, (which may lead to “scurvy”) is one of the oldest-known nutritional disorders. It remains an issue worldwide – although it is less common in developed countries compared to developing countries. It’s important to understand scurvy as it still occurs and it can be fatal if unrecognized and untreated.

It is really not clear precisely how common vitamin C deficiency is. Some studies suggest estimates of 1-2% in developed countries but other studies have suggested much higher (8-15%). In Canada the number may be around 3%. A 2009 study by Schleicher et al suggested that in the United States, the number is around 7-8% (but upwards of 10-17% in low income individuals in the US). The prevalence of vitamin C deficiency in low income countries also has a great variation depending on the study but ranges from 15-80%. Most studies in developing countries put the figure around 40-80%.

Germany, Austria, England, France Canada have populations with some of the highest vitamin C levels in the world. India, Uganda, Russia, Nigeria have populations with some of the lowest vitamin C levels.

Scurvy in Days of the Sailor

In the long transoceanic voyages of the past, sailors dreaded the disease scurvy more than any other disease. It is said that scurvy killed more than two million sailors between the 1500 and the mid 1800s.

Scurvy was so common that shipowners and governments assumed a 50% death rate from scurvy for their sailors on any major voyage. According to author and historian Stephen Bown scurvy “was responsible for more deaths at sea than storms, shipwrecks, combat, and all other diseases combined.”

The first symptom of scurvy in sailors was lethargy, irritability and a feeling not to eat. The body feels weak and the joints ache.  The bruises come later.  

It was the Scottish doctor, Dr James Lind of the British Royal Navy in the 1700s who is often credited for solving the mystery of scurvy. The reality is that others before him had identified the benefits of citrus fruits to cure scurvy but the concept didn’t really catch on all that well.

Although Dr. Lind did not discover the benefits of citrus fruits, he was the first to study it in a systematic way. This is said to be was one of the world’s first clinical trials.

Lind thought that scurvy was somehow related to a decay in the body’s tissues (called putrefaction) that might be helped out by consuming acids. He conducted a clinical study of 12 sailors with 6 groups. There were 2 people in each group. Everyone received the same basic diet but there was a modification in each group.  Group 1 received a quart of cider, group 2 received 25 drops of sulfuric acid, group 3 received 6 spoonfuls of vinegar, group 4 received seawater, group 5 received 2 oranges and 1 lemon and group 6 received a spicy paste and barley water. Group 5 ran out of fruit after 6 days but at the time 1 had full recovered and one had almost recovered. 4 groups had no effect and the cider group had some mild effect.   

Shortly after this experiment, Lind retired from the Navy and practised privately as a physician. In 1753, he published A treatise of the scurvy. Unfortunately, this document was mostly ignored.

What are the Definitions of Vitamin C Deficiency and insufficiency

The cuts off levels are  ≤23–28 µmol/L ((≤0.6 mg/dL) for hypovitaminosis C (insufficiency) and ≤11 µmol/L (≤0.2mg/dL) for vitamin C deficiency.

Who is at Risk For Vitamin C Deficiency?

There is very little ability of the body to store vitamin C. It must be taken in from the diet and therefore is said to be an ‘essential’ vitamin. Poor dietary intake will lead to insufficiency and deficiency. Signs and symptoms of scurvy usually develop after 1-3 months of insufficient vitamin C intake.

Populations at risk include:

·      Individuals with food insecurity

·      Individuals with poor nutrition

·      Individuals with alcohol use disorder,

·      individuals with eating disorders.   

·       Babies only fed cow's milk

·       Seniors only consuming tea and toast diet

·       Individuals  who are not able to afford fruits and vegetables

·       Individuals who do not consume fresh uncooked fruits and vegetables

·       Smokers

·       Type 1 diabetes who have high vitamin C requirements

·       Individuals with disorders of the GI tract like inflammatory bowel disease.

·       Individuals with iron overload, which leads to wasting of vitamin C by the kidneys

·       Individuals with restrictive diets, food allergies

·       Patients receiving dialysis

Role of  Vitamin C in Health: What does vitamin C do exactly?

In general, vitamin C has a role in wound healing, immune function, iron absorption, bone health, blood vessel health and more. Vitamin C has a key role in many of the body’s functions.

One of the more famous of the vitamin C functions is it’s role in collagen synthesis. Collagen type IV is the main constituent of blood vessel walls, skin. It is part of the basement membrane. Vitamin C has a role in making sure this is formed properly.

Vitamin C allows hydroxylation and crosslinking of pro-collagen catalyzed by lysyl hydroxylase.  Lack of vitamin C impairs collagen synthesis because it decreases transcription of pro-collagen. Additionally, a lack of ascorbic acid has other effects on collagen synthesis as well.

Vitamin C also has a role in iron absorption so many individuals who are vitamin C deficiency have evidence of iron deficiency too.

Vitamin C is also a cofactor for a family of biosynthetic and regulatory metalloenzymes, including those involved in the synthesis of catecholamine and peptide hormones. Tissues with the highest concentrations of vitamin C include the brain, adrenals and pituitary gland. This reflects a key function of vitamin C in hormone production.

In addition to effects on collagen, new research has also indicated an important role for vitamin C in regulating gene transcription and the methylation of DNA and histones- therefore having ‘genetic’ and ‘epigenetic’ effects.  As a result, vitamin C has the potential to regulate thousands of genes in the body.

Clinical Manifestations Vitamin C Deficiency

As humans, we need vitamin C to survive. The vitamin C pool in the body is usually depleted in 4 to 12 weeks if one stops the intake of this vitamin. Vitamin C is said to be an “essential” vitamin. Vitamin C deficiency itself manifests symptomatically after 8 to 12 weeks of inadequate intake and presents first as irritability, lethargy and anorexia.

This general feeling of being unwell is followed later by the classic constellation of corkscrew hairs, perifollicular hemorrhage, and gingival bleeding. This triad  is highly suggestive of vitamin C deficiency. Skin bruising is very common.

Vitamin C deficiency impacts blood vessels and bone.  The key feature of scurvy is hemorrhage which can occur in almost any organ. There can be extracutaneous hemorrhage in muscles, bones, eyes (retrobulbar hemorrhages), heart (hemopericardium, cardiac tamponade), and the nervous system (hemorrhage into nerve sheaths) .

Further, bone formation is altered and becomes brittle.

Other manifestations can occur too. These include neuropathy, joint swelling, myalgias, impaired wound healing.

Skin findings in scurvy

Because of the disruption of disulfide bond formation, both ‘corkscrew’ and ‘swan-neck’ hairs occur. Perifollicular hemorrhages are often found on the lower extremities because capillary fragility cannot withstand the gravity-dependent hydrostatic pressure.

The collagen abnormality that is part of scurvy leads to blood vessel fragility, easy bruising and poor wound healing.  Some patients have extensive bruising.

Other Clinical Findings in Patients with Vitamin C Deficiency

Patients who are deficient in vitamin C are often deficient in iron and folate. This is because vitamin C and folate are often found in the same foods and vitamin C also promotes iron absorption. The vast majority of patients with vitamin C deficiency have an anemia. In fact, anemia is seen in 75% of patients with scurvy, making it the second most most common laboratory finding in scurvy (after low vitamin C).  

Diagnosis of Vitamin C Deficiency

The diagnosis of scurvy can be confirmed by a blood test.

The cuts off levels are  ≤23–28 µmol/L ((≤0.6 mg/dL) for hypovitaminosis C (insufficiency) and ≤11 µmol/L (≤0.2mg/dL) for vitamin C deficiency.

Skin biopsies are often done to aid in diagnosis. Biopsy specimens of skin lesions often demonstrate follicular hyperkeratosis, perifollicular hemorrhage, a proliferation of blood vessels, and coiled hair follicles.

Histology findings from a patient with scurvy. Biopsy showed stratum corneum hyperkeratosis with perifollicular erythrocyte extravasation and a scant superficial perivascular mononuclear infiltrate From Tembunde Y et al. Scurvy: A Diagnosis Not to Be Missed. Cureus. 2022 Dec 28;14(12):e33050. used with creative commons license.

Serum testing for low plasma vitamin C (less than 0.2 mg/dL) is usually consistent with scurvy.

However, one must be aware that the recent intake of vitamin C or recent supplementation with vitamin C may elevate plasma levels and not be reflective of a prior prolonged deficit. The level of vitamin C in leukocytes is more accurate when assessing the sparse vitamin C stores as they are less affected by acute dietary changes. This leukocyte vitamin C testing is not available in many centers.  

Blood tests in a patient with presumed vitamin C deficiency should not stop at testing serum ascorbic acid levels but include vitamin B12, folate, calcium, zinc, and ferritin. These levels are generally also low. Many times tests for bleeding and coagulation and vasculitis are often ordered given that these hemorrhages can so closely resemble a vasculitis or bleeding issues.

Treatment and Prevention of  Vitamin C Deficiency

The treatment of vitamin C deficiency involves given iron. This can be achieved with 250-1000 mg per day of vitamin D. Symptoms start resolving within days and  spontaneous bleeding improves within days to weeks. It make take corkscrew hairs up to 1 month to resolve. Patients feel remarkably better within a few days.

Attention to a good diet or ongoing vitamin C supplementation may prove helpful. Generally speaking the goal should be to correct the underlying issue that contributed to the vitamin C deficiency in the first place.

The Recommended Dietary Allowance for adults 19 years and older is 90 mg daily for men and 75 mg for women. For pregnancy and lactation, the amount increases to 85 mg and 120 mg daily, respectively. Smoking can deplete vitamin C levels in the body, so an additional 35 mg beyond the RDA is suggested for smokers. A small orange has about 50  mg of vitamin C and large orange has about 100 mg of vitamin C.

REFERENCES

Yazmeen Tembunde et al. Scurvy: A Diagnosis Not to Be Missed. Cureus. 2022 Dec 28;14(12):e33050.

https://www.ncbi.nlm.nih.gov/books/NBK493187/

Schleicher R et al. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). Am J Clin Nutr. 2009 Nov;90(5):1252-63.

https://www.sciencehistory.org/distillations/the-age-of-scurvy

https://en.wikipedia.org/wiki/James_Lind

ROWE AND CARR. Global Vitamin C Status and Prevalence of Deficiency: A Cause for Concern?Nutrients. 2020 Jul; 12(7): 2008.