The Science

Integrative Medicine. Backed by science.

Vitamin D • Vitamin C • Zinc • Quercetin

Vitamin D and Respiratory Tract Infection

The bottom line:

  • Vitamin D deficiency is common, affecting nearly one third of Australians
  • Routine vitamin D3 supplementation has also been shown to be safe and effective in preventing acute respiratory tract infections such as common cold and flu.
  • If you’d like to know more about your vitamin D status and dose requirements, we recommend talking to your doctor

The article:

Vitamin D deficiency has been recognised as a global public health concern with nearly a third of Australians over the age of 25 shown to have low levels of vitamin D. This finding was demonstrated in a large population-based study conducted in 2012 which assessed vitamin D levels in more than 11,000 Australians. Vitamin D deficiency was found to affect 31% of Australians, with the highest incidence in women (39% were deficient in vitamin D overall). Even more astonishing was the finding that nearly sixty percent of women were shown to be deficient in vitamin D over the period of winter to spring(1). So what is the link between vitamin D and immunity? And could all this deficiency be putting people at risk?

The role of vitamin D in regulating immune function has been described in various literature reports. Vitamin D receptors have been identified on various immune cells including macrophages, monocytes, dendritic cells, and T and B lymphocytes, all of which are vital to enable direct killing of pathogens and development of long standing immunity through production of antibodies(2).

Routine vitamin D3 supplementation has also been shown to be safe and effective in preventing acute respiratory tract infection. This was concluded from a large meta-analysis of 25 high quality randomised, double-blind placebo-controlled trials including 10,933 subjects. Vitamin D supplementation reduced the incidence of respiratory infection in all participants, including those with ‘adequate’ levels of vitamin D. It also had a profound effect in those who were vitamin D deficient. It is important to know that daily and weekly supplementation is effective, but larger infrequent doses (e.g. once a month) are not effective(3).

So how much vitamin D do you need?

The bottom line is that the only way to know if you are deficient in vitamin D is to see your doctor and get a simple blood test which will help determine the dose of vitamin D required to maintain healthy levels. In Australia, vitamin D deficiency refers to levels lower than 50nmol/L (or 20ng/mL for those readers in the USA) with levels greater than 75nmol/L considered optimal(4). Daily vitamin D3 doses of 1000IU (25mcg) per day can maintain people in the healthy range provided they are not already deficient in vitamin D. However, there is some evidence that optimal health benefits of vitamin D may be obtained in the range of 100-150 nmol/L which may require daily dosing of 4000-6000IU per day. Toxicity from excessive oral intake of vitamin D is possible, however, no evidence of vitamin D toxicity has been shown with doses of up to 4000IU per day. In Australia, the maximum daily dose of vitamin D recommended for general use is 1000IU per day unless advised otherwise by your doctor(5).

Ultimately, the decision to take vitamin D supplements or not rests with you. If you’d like to know more about your vitamin D status and dose requirements, we recommend talking to your doctor.

References

  1. Daly R, Gagnon C, Lu Z, Magliano D, Dunstan D, Sikaris K et al. Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study. Clinical Endocrinology [Internet]. 2012;77(1):26-35. Available from: https://pubmed.ncbi.nlm.nih.gov/22168576/
  2. Charoenngam N, Holick M. Immunologic Effects of Vitamin D on Human Health and Disease. Nutrients [Internet]. 2020;12(7):2097. Available from: https://www.mdpi.com/2072-6643/12/7/2097/htm
  3. Martineau A, Jolliffe D, Hooper R, Greenberg L, Aloia J, Bergman P et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ [Internet]. 2017:i6583. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310969/
  4. RCPA - Vitamin D [Internet]. Rcpa.edu.au. 2020 [cited 4 December 2020]. Available from: https://www.rcpa.edu.au/Manuals/RCPA-Manual/Pathology-Tests/V/Vitamin-D
  5. Vitamin D deficiency in adults [Internet]. NPS Medicinewise. 2010 [cited 4 December 2020]. Available from: https://www.nps.org.au/australian-prescriber/articles/vitamin-d-deficiency-in-adults-1
Vitamin D3

Vitamin C

The truth about vitamin C - a review of the evidence

The bottom line:

  • Dozens of studies have demonstrated the immunomodulating and antiviral effects of vitamin C as well as its potential role as an antioxidant, protecting against oxidative stress in the event of infection.
  • Regular use of vitamin C can reduce the duration and severity of common cold symptoms.
  • Clinical studies have shown vitamin C can halve the incidence of common cold following periods of extreme physical exercise (50% reduction in the incidence of common cold in select population groups).

The case for taking vitamin C supplements has long been a topic of debate among doctors and scientists and yet, vitamin C supplements remain widely used in the general community. Here, we review the evidence on the benefits of vitamin C supplementation and debunk some myths about this commonly used vitamin.

Vitamin C gained great public interest in the 1970s after Nobel prize winner Linus Pauling released a book titled ‘Vitamin C and the Common Cold’. Following this, a number of clinical trials were conducted which produced conflicting results and some confusion regarding the benefits of vitamin C supplementation in treating the common cold(1,2).

Nevertheless, dozens of studies have demonstrated the immunomodulating and antiviral effects of vitamin C as well as its potential role as a physiological antioxidant, protecting against oxidative stress in the event of infection(2). As such, the mechanism by which vitamin C may provide a protective effect during infection remains highly physiologically plausible, but what proven clinical effect (if any) has been demonstrated in humans?

In 2013, a large systematic review was conducted to determine whether vitamin C supplementation (at a dose of 200mg per day or greater) reduced the severity, duration or incidence of common cold. In this review, an analysis of 29 placebo-controlled clinical trials involving 11,306 participants revealed that regular vitamin C supplementation on a daily basis did not significantly reduce the incidence of common cold in the general population (i.e. it did not change how often people caught colds). However, regular supplementation was shown to significantly reduce the duration of common cold symptoms by 14% in children and by 8% in adults. Regular supplementation also assisted in reducing the severity of common cold symptoms. Of particular significance was the benefit observed in clinical studies which assessed participants exposed to short periods of extreme physical stress (e.g. marathon runners, skiers and soldiers) in which an analysis of 598 participants taking regular vitamin C had a greater than 50% reduction in the incidence of common cold. That is, the risk of acquiring common cold in these circumstances was halved overall compared to those taking placebo(2).

The authors of this study went on to conclude that vitamin C supplementation may be beneficial for short term use for people who engage in severe physical exercise to help prevent the occurrence of common cold. They also suggested that it may be worthwhile for patients with acquired common cold to test the benefits of vitamin C in reducing the duration and severity of their symptoms given the consistency of improvement in severity and duration of common cold symptoms with regular supplementation(2).

In summary, the findings of this comprehensive review of the literature has shown that:

  • Regular use of vitamin C has a modest but clinically significant effect in reducing common cold duration and severity in both children and adults.
  • Vitamin C supplementation may have significant benefits in select populations who engage in intense physical activity, by reducing the incidence of common cold in the post-exercise period.

References

  1. Pauling L. Vitamin C and the common cold. San Francisco: Freeman; 1970.
  2. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews [Internet]. 2013;. Available from: https://pubmed.ncbi.nlm.nih.gov/23440782

The Role of Zinc in Respiratory Infection and Immunity

The bottom line:

  • Zinc is an essential micronutrient which plays a role in the regulation of immune function.
  • Zinc deficiency is common. The World Health Organisation (WHO) estimates that up to one third of the world’s population is deficient in zinc(5).
  • In Australia, zinc deficiency is more common in older men(6).
  • Several studies suggest that zinc may assist with fighting respiratory tract infection such as common cold and flu (read on to learn more).

Zinc is an essential micronutrient which plays a role in the regulation of immune function. A substantial amount of scientific literature has documented the beneficial role of zinc in fighting respiratory tract infections such as common cold and flu. This review is intended to summarise available research on the role of zinc in immunity and respiratory infection.

In 2017, a large meta-analysis was conducted reviewing seven randomised, double-blind, placebo-controlled clinical trials of robust methodological quality including 575 participants with naturally acquired common cold. The seven clinical trials were conducted by six different research groups over three decades and all seven clinical trials concluded that supplementation with oral zinc lozenges decreased common cold duration by at least 33%(1).

In 2012, a systematic review and meta-analysis of 17 trials involving a total of 2121 participants found moderate quality evidence to suggest that orally administered zinc reduced the duration of symptoms of the common cold compared to placebo(2).

A similar systematic review conducted by Singh & Das in 2013 included 16 therapeutic trials (randomised, double-blind and placebo controlled trials) and found that zinc administered within 24 hours of symptom onset reduced the duration of common cold symptoms in healthy people, regardless of the type of preparation used (lozenges, syrup or tablets), and concluded that tablet forms of zinc were better tolerated than lozenges. It should be noted that the majority of research to date has been conducted using high dose zinc lozenges (greater than 75mg elemental zinc per day) and further clinical trials are needed to further evaluate the benefits of zinc tablets(3). In 2009, a clinical trial to assess the efficacy of zinc tablets in the treatment and prevention of common cold in 200 primary school children showed that regular supplementation with zinc tablets (equivalent to 10mg elemental zinc) reduced the frequency and severity of common colds and resulted in less missed school days and less antibiotic use when compared to children taking placebo(4).

Furthermore, zinc deficiency is common. The World Health Organisation (WHO) estimates that up to one third of the world’s population is deficient in zinc and an Australian study of 497 Tasmanian adults showed that zinc deficiency was present in 18% of men over the age of 50 and 30% of men over the age of 70(5).

A number of clinical trials have documented effects of zinc supplementation in improving cell-mediated immunity and reducing respiratory infection in elderly populations. A clinical trial conducted in 2015 involving more than a hundred nursing home residents in Italy demonstrated that 25mg elemental zinc (as zinc sulfate) improved cell-mediated immune response by increasing the number of T helper cells and cytotoxic T cells(6). Another study showed that supplementation with 45mg elemental zinc per day (as zinc gluconate) significantly reduced the occurrence of infections in older people, including respiratory infection, over a 12 month period(7).

Given the prevalence of zinc deficiency in the general community; the clear association between zinc deficiency and the incidence of respiratory infection; and the benefits of zinc supplementation in reducing infectious disease, assessment of zinc status and appropriate supplementation with zinc should be considered an issue of public health concern.

References

  1. Hemilä H. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage. JRSM Open [Internet]. 2017;8(5):205427041769429. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418896/
  2. Science M, Johnstone J, Roth D, Guyatt G, Loeb M. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. Canadian Medical Association Journal [Internet]. 2012;184(10):E551-E561. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394849/
  3. Singh M, Das R. Zinc for the common cold. Cochrane Database of Systematic Reviews [Internet]. 2013;. Available from: https://pubmed.ncbi.nlm.nih.gov/23775705/
  4. Vakili R, Vahedian M, Khodaei G, Mahmoudi M. Effects of zinc supplementation in occurrence and duration of common cold in school aged children during cold season: a double-blind placebo-controlled trial. Iranian Journal of Paediatrics [Internet]. 2009;19(4):376-380. Available from: https://www.sid.ir/en/journal/ViewPaper.aspx?ID=164643
  5. Beckett J, Ball M. Zinc status of northern Tasmanian adults. Journal of Nutritional Science [Internet]. 2015;4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463943/
  6. Fortes C, Forastiere F, Agabiti N, Fano V, Pacifici R, Virgili F et al. The Effect of Zinc and Vitamin A Supplementation on Immune Response in an Older Population. Journal of the American Geriatrics Society [Internet]. 1998;46(1):19-26. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1532-5415.1998.tb01008.x
  7. Prasad A, Beck F, Bao B, Fitzgerald J, Snell D, Steinberg J et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. The American Journal of Clinical Nutrition [Internet]. 2007;85(3):837-844. Available from: https://pubmed.ncbi.nlm.nih.gov/17344507/
Zinc

Quercetin

Quercetin - an antioxidant with antiviral activity

The bottom line:

  • Quercetin is a well-known antioxidant and an abundant flavonoid found in several foods derived from plants.
  • Laboratory and animal studies have demonstrated quercetin’s antiviral and antibacterial properties.
  • Clinical trials have shown that Quercetin can reduce the incidence of viral upper respiratory tract infection such as the common cold following periods of intensive exercise or high mental stress.

Quercetin is a well-known antioxidant and an abundant flavonoid found in several foods derived from plants. Robust scientific evidence has demonstrated Quercetin’s physiological properties including anti-inflammatory, antioxidant, anti-pathogenic and immunomodulatory effects. Having been previously identified as playing an important role in the protection of plants from bacterial and fungal infection; in vitro (i.e. laboratory-based) and animal studies have also demonstrated quercetin’s antiviral and antibacterial properties(1,2).

While research to establish the role of Quercetin in the treatment of viral disease in humans is still in its infancy, preliminary data suggest that Quercetin may be beneficial in the prevention of upper respiratory tract infections. Research has shown that Quercetin can reduce the incidence of viral upper respiratory tract infection in the immediate post-exercise period following intensive exercise and in individuals suffering from high mental stress, conditions in which it is known that immune function is decreased and the incidence of viral infections is higher(3-6).

References

  1. Patrick R. FoundMyFitness Topic - Quercetin [Internet]. FoundMyFitness. 2020. Available from: https://www.foundmyfitness.com/topics/quercetin#quercetin-bioavailability-and-safety-profile
  2. Kinker B. Quercetin: A Promising Treatment for the Common Cold. Journal of Ancient Diseases & Preventive Remedies [Internet]. 2014;02(02). Available from: https://www.longdom.org/open-access/quercetin-a-promising-treatment-for-the-common-cold-2329-8731.1000111.pdf
  3. Heinz S, Henson D, Austin M, Jin F, Nieman D. Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial. Pharmacological Research [Internet]. 2010;62(3):237-242. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128946/
  4. Li Y, Yao J, Han C, Yang J, Chaudhry M, Wang S et al. Quercetin, Inflammation and Immunity. Nutrients [Internet]. 2016;8(3):167. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808895/
  5. Nieman D, Henson D, Gross S, Jenkins D, Davis J, Murphy E et al. Quercetin Reduces Illness but Not Immune Perturbations after Intensive Exercise. Medicine & Science in Sports & Exercise [Internet]. 2007;39(9):1561-1569. Available from: https://journals.lww.com/acsm-msse/Fulltext/2007/09000/Quercetin_Reduces_Illness_but_Not_Immune.18.aspx
  6. Nieman D, Henson D, Maxwell K, Williams A, Mcanulty S, Jin F et al. Effects of Quercetin and EGCG on Mitochondrial Biogenesis and Immunity. Medicine & Science in Sports & Exercise [Internet]. 2009;41(7):1467-1475. Available from: https://journals.lww.com/acsm-msse/Fulltext/2009/07000/Effects_of_Quercetin_and_EGCG_on_Mitochondrial.15.aspx

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