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Vitamin C: For optimal therapeutic benefit

 
Lisa Costa-Bir's picture

Vitamin C, well known for its immune support action, forms a major part of most Australian diets, leading to presumptions that clients are meeting nutritional requirements. While this essential vitamin has a plethora of other health benefits, more Australians may be deficient than we realise with the re- emergence of scurvy in modern day populations.

Vitamin C (also known ascorbic acid, AA) is a hydrophilic molecule that is vital for optimal functioning. Humans cannot synthesise vitamin C endogenously as they do not make the enzyme L-gulono-1,4 lactone oxidase which is essential for the biosynthesis of vitamin C.1 Instead, dietary vitamin C must be obtained to ensure daily adequate intake.

Measurement of vitamin C

  • Intake and storage of vitamin C may be measured by both plasma and leucocyte levels.

  • Leucocytes hold 50-100-fold higher vitamin C versus plasma.

  • Plasma is reflective of recent intake and does not reflect tissue and body stores reliably when compared to leucocyte ascorbic acid.3

The reference interval for vitamin C used by the Royal College of Pathologists of Australasia is generally between:

    • Plasma: 30-80 μmol/L

    • Leucocytes: 1.1-3.0 μmol/109 4

Vitamin C deficiency – a rarity?

It is generally assumed that vitamin C deficiency is rare, however, research suggests otherwise highlighting a rising incidence in Australia.

A 2023 retrospective study examining serum vitamin C status in 13,000 individuals tested in a public hospital in NSW, observed vitamin C insufficiency in 29.9% and deficiency in 24.5% of individuals.5 Several studies looking at serum vitamin C levels found sub-optimal levels in the following cohorts:

  • 50% of individuals with diabetic foot ulcers visiting Westmead Hospital, Sydney.6

  • 50% of a cohort of patients in a mental health setting in South Australian had vitamin C levels lower than 26 μmol/L.7

  • 30% of individuals with periodontal disease consulting a periodontal clinic in Sydney.8

The rising incidence of vitamin C insufficiency may be due to several factors including dietary changes (e.g. inadequate consumption of fruit and vegetables), increased chronic illness causing malabsorption, and/or increased requirements.9

Modern agricultural practices are considered to be a contributing factor to reduced vitamin C sufficiency, with research suggesting a 15-30% decrease in vitamin C content in a variety fruits and vegetables over the last 50 years due to nutrient depletion as a result of poor soil quality due to over farming.10

Absorption of vitamin C

Plasma and tissue concentrations of vitamin C are mediated by gastrointestinal absorption. Absorption takes place primarily in the distal ileum,18 followed by renal reabsorption and excretion via the urine.19 Subsequently it is unsurprising that individuals with irritable bowel disease commonly exhibit insufficient serum vitamin C levels.20,21

Bioavailability

  • Vitamin C bioavailability declines rapidly as the dose increases.

  • Small frequent doses appear more efficacious than large doses. Low dose of 200-400 mg results in 100% absorption, however if 500 mg is exceeded, bioavailability reduces, decreasing to approximately 30% when 1000 mg

    is consumed orally in one bout. This is due to maximal saturation of the intestinal transporter SVCTI.22

  • Because vitamin C is water soluble, almost all the absorbed dose is excreted in urine within 24 hours.23 It is therefore important to be aware of a person’s daily vitamin C intake and ensure they are replenishing levels daily.

PERFECT PAIRINGS

Bioflavonoids

The benefits of vitamin C are enhanced when used in combination with bioflavonoids compared to the use of vitamin C alone.38

Glutathione regeneration: prescribing vitamin C and glutathione together

As powerful antioxidants, both vitamin C and glutathione play an important role in cellular antioxidant defence systems. Both antioxidants appear to augment each other, assisting with the transformation from their reduced forms and the recycling

of one another.39 Supplementation with vitamin C has been shown to increase plasma glutathione levels, enhancing antioxidant activity. Deficiency of either vitamin C or glutathione appears to impede the action of the other.39

SAFETY CONSIDERATIONS

  • Vitamin C is generally well tolerated when used at low doses.40

  • Vitamin C 5–10 g/day orally may produce transient osmotic diarrhea.41

  • There is conflicting data regarding increased risk of oxalate containing kidney stones with use of vitamin C, however at low doses this is unlikely to occur.42

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References

1 Caritá AC, et al. Vitamin C: One compound, several uses. Advances for delivery, efficiency, and stability. Nanomedicine. 2020Feb;24:102117.
2 Eat For Health.gov.au, Vitamin C (Internet). Available from:https://www.eatforhealth.gov.au/nutrient-reference-values/nutrients/vita...
3 Plevin D & Galletly C. The neuropsychiatric effects of vitamin C deficiency: a systematic review. BMC Psychiatry. 2020 Jun18;20(1):315.
4 Vitamin C RCPA Pathology Manual (Internet). Available from: https://www.rcpa.edu.au/Manuals/RCPA-Manual/PathologyTests/V/Vitamin-C#:...,(may%20vary%20by%20laboratory).
5 Bhattacharyya P, et al. Serum vitamin C status of people in New South Wales: retrospective analysis of findings at a public referral hospital. Med J Aust. 2023 Nov 20;219(10):475-481.
6 Gunton JE, Girgis CM, Lau T, Vicaretti M, Begg L, Flood V. Vitamin C improves healing of foot ulcers: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 2021 Nov 28;126(10):1451-1458. doi: 10.1017/S0007114520003815. Epub 2020 Sep 28. PMID:32981536.
7 Plevin D & Galletly C. The neuropsychiatric effects of vitamin C deficiency: a systematic review. BMC Psychiatry. 2020 Jun 18;20(1):315
8 Munday MR et al. A Pilot Study Examining Vitamin C Levels in Periodontal Patients. Nutrients. 2020 Jul 28;12(8):2255
9 Carr AC & Rowe S. Factors Affecting Vitamin C Status and Prevalence of Deficiency: A Global Health Perspective. Nutrients. 2020 Jul 1;12(7):1963.
10 Bhardwaj RL, et al. An Alarming Decline in the Nutritional Quality of Foods: The Biggest Challenge for Future Generations' Health. Foods. 2024 Mar 14;13(6):877
11 Lee E, et al. Vitamin C and glutathione supplementation: a review of their additive effects on exercise performance. Phys Act Nutr. 2023 Sep;27(3):36-43.
12 Gunton JE, Bechara N. Vitamin C insufficiency in Australia: underrated and overlooked? Med J Aust. 2023 Nov 20;219(10):463-464
13 Yosaee S, et al. The effect of vitamin C supplementation on mood status in adults: a systematic review and meta-analysis of randomized controlled clinical trials. Gen Hosp Psychiatry. 2021 Jul-Aug;71:36-42.
14 Plevin D & Galletly C. The neuropsychiatric effects of vitamin C deficiency: a systematic review. BMC Psychiatry. 2020 Jun 18;20(1):315.
15 Doseděl M et al. On Behalf Of The Oemonom. Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients. 2021 Feb 13;13(2):615.
16 Loganathan V, et al. Treatment efficacy of vitamin C or ascorbate given as co-intervention with iron for anemia - A systematic review and meta-analysis of experimental studies. Clin Nutr ESPEN. 2023 Oct;57:459-468.
17 Maxfield L, et al. Vitamin C Deficiency. [Updated 2023 Nov 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493187/
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19 Padayatty SJ, et al. Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone. Am J Clin Nutr. 2007 Jul;86(1):145-9.
20 Gordon BL, et al. Prevalence and factors associated with vitamin C deficiency in inflammatory bowel disease. World J Gastroenterol. 2022 Sep 7;28(33):4834-4845.
21 Dunleavy KA, et al. Vitamin C Deficiency in Inflammatory Bowel Disease: The Forgotten Micronutrient. Crohns Colitis 360. 2021 Feb 23;3(1):otab009.
22 Cerullo G, et al. The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19. Front Immunol. 2020 Oct 28;11:574029.
23 Padayatty SJ & Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis. 2016 Sep;22(6):463-93.
24 Plevin D & Galletly C. The neuropsychiatric effects of vitamin C deficiency: a systematic review. BMC Psychiatry. 2020 Jun 18;20(1):315.
25 Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov 3;9(11):1211
26 Bozonet SM, et al. Enhanced human neutrophil vitamin C status, chemotaxis and oxidant generation following dietary supplementation with vitamin C-rich SunGold kiwifruit. Nutrients (2015) 7:2574–88.
27 Yingcharoenthana, S. et al. A split-mouth randomized clinical trial to evaluate the effect of local and systemic administration of vitamin C on extraction wound healing. J. Oral Sci. 2021, 63, 198–200
28 Loganathan V, et al. Treatment efficacy of vitamin C or ascorbate given as co-intervention with iron for anemia - A systematic review and meta-analysis of experimental studies. Clin Nutr ESPEN. 2023 Oct;57:459-468.
29 Low, M. et al. Daily iron supplementation for improving anaemia, iron status and health in menstruating women. Cochrane Database of Systematic Reviews 2016, Issue 4, No:CD009747
30 Hurrell R. How to ensure adequate iron absorption from iron-fortified food. Nutr. Rev. 2002;60:S7–S15.
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33 Moritz, B., et al. The role of vitamin C in stress-related disorders. J Nutr Biochem. 2020 Nov;85:108459
34 Brody S, et al. A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress. Psychopharmacology (Berl). 2002 Jan;159(3):319-24
35 Bechara N, et al. A Systematic Review on the Role of Vitamin C in Tissue Healing. Antioxidants (Basel). 2022 Aug 19;11(8):1605.
36 Gunton, J.E. et al. Vitamin C improves healing of foot ulcers: A randomised, double-blind, placebo-controlled trial. Br. J. Nutr. 2021, 126, 1451–1458
37 Kaźmierczak-Barańska J, Boguszewska K, Adamus-Grabicka A, Karwowski BT. Two Faces of Vitamin C-Antioxidative and ProOxidative Agent. Nutrients. 2020 May 21;12(5):1501.
38 Murray, M. 81 - Flavonoids—Quercetin, Citrus Flavonoids, and Hydroxyethylrutosides (Pg 613-619.e2) in Pizzorno, J. & Murray, M. (2020) Textbook of Natural Medicine (5th Ed.) Churchill-Livingstone
39 Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999 Apr 21;281(15):1415-23
40 Olczak-Pruc M, et al. Vitamin C Supplementation for the Treatment of COVID-19: A Systematic Review and Meta-Analysis. Nutrients. 2022 Oct 10;14(19):4217..
41 Doseděl M, et al. On Behalf of The Oemonom. Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients. 2021 Feb 13;13(2):615
42 Chmiel JA, Stuivenberg GA, Al KF, Akouris PP, Razvi H, Burton JP, Bjazevic J. Vitamins as regulators of calcium-containing kidney stones - new perspectives on the role of the gut microbiome. Nat Rev Urol. 2023 Oct;20(10):615-637

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Lisa Costa-Bir's picture
Lisa Costa-Bir
Lisa is a practicing naturopath based in Sydney, Australia. She specialises in women’s health and auto-immunity in her clinical work, as well as working as an academic lecturer and clinical supervisor at Torrens University and Endeavour College of Natural Therapies in Sydney. She is also an Adjunct Fellow of the National Centre for Naturopathic Medicine (SCU). She has a Masters of Women’s Health (UNSW), as well as Graduate Diploma of Applied Science in Naturopathy (UWS), and a Bachelor of Applied Science in Naturopathy (UWS). Lisa has written numerous naturopathic articles and was a contributing author for the widely used naturopathic textbooks “Clinical Naturopathic Medicine” and “Advanced Clinical Naturopathic Medicine”. Her greatest passion is psycho-neuro-immunology and understanding how natural interventions can be used to modulate neuro-endocrine-immune responses for optimal patient heath. In her spare time, Lisa enjoys doing Muay Thai, spending time out in nature and making TikTok videos with her daughter and her cat Milo.