I’ve been getting questions about whether to take supplements, which to take, how much to take, what form, and so forth. The short (and slightly annoying) answer is: it’s different for everyone, and you should consult with your healthcare provider for personalized nutrition and supplement advice. While they are widely available to all of us, supplements can actually interact with medications that some of us are taking, so it’s always safest to check. Supplements are usually most effective for those with a deficiency, and are not necessary (or necessarily appropriate) for everyone. With that said, I will now talk you through the evidence for and against certain supplements in viral and respiratory infections, and give you some details on each so that you can decide for yourself whether or not they might be helpful for you. The main three micronutrients for immune support are well known: the vitamins C and D, and the mineral zinc. There are also some lesser known substances (a polyphenol, a trace mineral, an amino acid and a hormone) that are currently getting attention in the current COIVD-19 pandemic, which I’ll touch on briefly after talking about the big three. Vitamin C
Vitamin C is a powerful antioxidant, and it is important to get enough for healthy immune function. However, the evidence for taking vitamin C supplements to prevent colds is mixed - in those at risk for low vitamin C status (e.g. smokers and the elderly), or those under extreme physical stress, supplementation may reduce the incidence of colds, but there isn’t compelling evidence that it does much preventively for the rest of us. That being said, those who do supplement with vitamin C seem to have shorter colds and suffer with fewer symptoms than those who don’t (1). While this might sound contradictory, what it essentially means is: if you take vitamin C, you may still get just as many colds as other people, but they might not last as long or be as bad. Dosage is important here too: studies on lower dose supplementation (<1000 mg/day) typically report fewer benefits than studies at higher doses (2). Research on vitamin C for pneumonia and other lower respiratory diseases goes back decades, with clinical trials finding an 80% lower incidence of pneumonia in those subjects receiving oral vitamin C (> 1 g/d) (3). Based on this background evidence and their own clinical observations of benefit, doctors in China are currently running multiple clinical trials to assess the efficacy of high dose IV vitamin C against COVID-19 (4), where pneumonia is a primary complication of infection (5). Just this week, news emerged that hospitals in the USA are now starting to use high dose vitamin C for COVID-19 patients too (6) (less than a week after claims that it might be useful were uproariously ‘debunked’ by the same publications, I might add.) Adult RDA: males 90 mg/d, females 75 mg/d (smokers + 35 mg/d). These are minimums needed to prevent deficiency (scurvy) - there are some who believe it should be higher than this, due to the amount of oxidative stress we experience in modern life (7). Food sources: bell peppers (1/2 cup = 95 mg), oranges (1 medium = 70 mg), kiwi fruit (1 medium = 64 mg), broccoli (1/2 cup, cooked = 51 mg), strawberries (1/2 cup = 49 mg), Brussels sprouts (1/2 cup, cooked= 48 mg), grapefruit (1/2 medium = 39 mg) and cauliflower (1/2 cup = 26 mg). Risk of deficiency: Low. Deficiency is extremely rare in the USA. Even those with suboptimal diets manage to get enough vitamin C from foods, on the whole. Risk of toxicity with supplementation: Low. Vitamin C is water soluble, excess will be eliminated in urine. Excessively high doses may cause nausea and loose stools. Official safe upper intake level is 2 g/d, but many studies report using doses of 4-8 g/d with no adverse effects. Form: If you decide to take larger amounts, try taking in divided doses throughout the day for better absorption, and with food, otherwise they might make you feel nauseous. Buffered vitamin C is designed to minimize the risk of nausea. Vitamin DThe ‘sunshine vitamin’ is not technically a vitamin, it’s a steroid hormone that our skin synthesizes when exposed to sunlight. It supports the immune system by stimulating production of antimicrobial peptides that live in the respiratory tract (and throughout the body), and also by preventing excessive expression of inflammatory cytokines (8) (AKA a ‘cytokine storm’). There is compelling evidence that taking vitamin D reduces the risk of common respiratory infections: a thorough review of clinical studies found that vitamin D supplementation reduced the incidence of colds by around 50% compared with placebo (9), and those who are deficient received the greatest benefits from supplementation (10). Most respiratory infections (including COVID-19) occur in the winter months, when vitamin D levels dip with fewer daylight hours. An Italian researcher (11) recently noted that the incidence of severe vitamin D deficiency in Italy is high, where the death toll from COVID-19 has also been high. Vitamin D deficiency is known to be associated with worse outcomes in critical illnesses, with higher rates of acute respiratory failure and more time needed on a ventilator, as well as higher fatality rates (12). The good news, is, interventional trials suggest that supplementation with high dose vitamin D3 (the active form) may improve outcomes for patients critically ill patients in ICUs (13); it remains to be seen if that will be true for COVID-19. Unfortunately, this isn’t like vitamin C, where deficiency is a rare phenomenon: more than 40% of US adults have vitamin D deficiency, and those percentages soar for those with darker skin tones (~70% of Hispanic Americans and ~80% of African Americans) (14). Blood levels lower than 30 nmol/L (or <12 ng/mL) are considered deficient, leading to rickets in young children and osteomalacia (soft bones) in adults. Levels between 30-50 nmol/L (or 12-20 ng/mL) are considered insufficient, and could also use a top up. Adult RDAs: under 50 years old = 600 IU/d; over 50 years old = 800 IU/d. Food sources: very few foods contain vitamin D3. Oily fish is one source (3 oz of salmon = 570 IU) along with fish oils (1 tbsp cod liver oil = 1,260 IU). A little bit can be found in egg yolks (I large egg = 45 IU) and cheese (1 oz cheddar = 12 IU). Mushrooms contain D2, an inferior form that the body has to convert (1/2 cup white mushrooms = 365 IU). Most milks in the US are fortified with vitamin D (1 cup = 100-140 IU), but check that it’s with D3 not D2, and know that vitamin D is fat soluble, which means that you probably won’t absorb as much vitamin D from fortified fat-free milk than fortified whole milk. Sun exposure is the most effective method of getting adequate vitamin D (15). The amount of exposure needed is highly variable based on personal circumstances, but it is estimate that 10-30 minutes per day between 10am and 3pm, a couple of times per week, with face and limbs exposed, will maintain adequate blood levels. Apps like DMinder can calculate personalized recommendations for sun exposure time based on an individuals D levels, current latitude, skin tone, and local weather reports. Risk of deficiency: High. Deficiency is very common in the US, particularly for those with darker skin, high BMI, the elderly, those living at more northern latitudes, and during the winter months. Risk of toxicity with supplementation: Low. Vitamin D is fat soluble, so it can accumulate in tissues and lead to toxicity. However, the blood level considered toxic is >500 nmol/L (>200 ng/mL), ten times the recommended level that most people are struggling to reach, meaning that toxicity is fairly unlikely. Some adverse effects are reported when blood levels exceed 75-100 nmol/L, so keeping within that limit is probably sensible. For supplementation, the safe upper limit is set at 4,000 IU/d for adults, but taking higher doses for short periods is not shown to cause problems, and therapeutic dosing (in cases of deficiency) is often in the region of 2,000-10,000 IU/d. Form: D3 is the ideal form; because it’s fat-soluble, oil-based drops are a great option for optimal absorption. If your levels are within normal range then supplementing with the RDA may be sufficient for maintenance, but doses of 2000 IU/d are often recommended to maintain borderline levels (if you are diagnosed with a deficiency your healthcare provider can advise the right amount for you). ZincZinc plays a role in almost every facet of the immune system, and may reduce the duration of respiratory infections and the severity of symptoms, particularly for those who are deficient. Having low zinc status depresses immune function and leaves you with increased susceptibility to pneumonia and other infectious diseases (16), so it is important to get enough. The elderly are one group at risk for inadequate zinc due to lower intakes and decreased absorption associated with aging (17), and the elderly are the demographic hardest hit by COVID-19. One observational study looked at the relationship between zinc levels in the elderly and rates of pneumonia over the course of a year, finding that those with low levels were more likely to get pneumonia and took longer to recover, plus they used twice the antibiotics of their peers with adequate zinc status (18). As for common colds, zinc lozenges and nasal preparations act as effective anti-virals by interfering with the ability of the rhinovirus to attach to the nose and throat, working particularly well if used in the first 24 hours (19). That being said, nasal zinc products have now been withdrawn from the market because overuse can lead to losing the sense of smell. This side effect is interesting because losing the sense of smell and taste is a common sign of zinc deficiency (a classic example of the Goldilocks principle of nutrition, where getting too much or not enough can cause the same unwanted effects). This sign of deficiency is of interest in the context of COVID-19, where loss of sense of smell and taste has recently been emerging as an early symptom of infection (20). I haven’t seen illness-induced zinc deficiency touted as a possible explanation, yet, but the idea isn’t without basis: zinc levels have been shown to drop at the onset of infections causing fever, and after pathogen exposure (21). The immune system responds in a variety of ways in this acute phase, many of which increase uptake of zinc (21), which could deplete stores fast. If someone’s zinc levels were low when they got exposed to the virus, this could accelerate a slide into deficiency during the initial stages of infection. Adult RDAs: males = 11 mg/d; females = 8 mg/d (likely higher for the elderly). Food sources: seafood and meat are good sources of zinc. Oysters (3 oz, fried = 74 mg), beef (3 oz, braised chuck roast = 7 mg), crab (3 oz, cooked = 6.5 mg), and chicken (3 oz, dark meat = 2.5 mg). For vegetarians, top sources are baked beans (1/2 cup = 3 mg), pumpkin seeds (1 oz = 2.2 mg), chickpeas (1/2 cup = 1.3 mg) and oatmeal (1/2 cup = 1 mg). Risk of deficiency: Moderate. Deficiency is not common in the US, but quite a few categories of people are at higher risk due to insufficient intake or absorption: vegetarians, pregnant and lactating women, people with gastrointestinal diseases and digestive disorders, alcoholics and the elderly. Risk of toxicity with supplementation: Moderate. The safe upper intake level is 40 mg/d. Higher levels for short periods are likely fine, but taking too much for too long can interfere with iron and copper status, as well as reduce immune function and HDL levels (the ‘good’ cholesterol). (22) Form: If you’re interested in taking zinc because your intake is low or marginal, supplements in tablet form are fine; if you’re interested in taking it because you feel like you’re coming down with something, lozenges are ideal, as they will coat the throat (which is where you want the zinc to go to work). If you can’t find lozenges, liquid zinc drops are also a good option - you can take straight, or mix with 1-2 oz of water and gargle. Other emerging nutrients in the fight against COVID-19![]() There are a few other compounds being explored as being potentially beneficial in COVID-19 infections. There is insufficient research at this stage to draw reliable conclusions about their benefits, but they are interesting nonetheless. Quercetin is a potent polyphenol with antioxidant and antiviral properties which appears to modulate immunity and inflammation in animal and lab studies (23). The shape of the quercetin molecule allows it to sit on the surfaces of cell walls and prevent the virus from docking. It has shown promise in the context of influenza A viruses (like H1N1), both preventively and therapeutically (24, 25, 26, 27) . In the context of coronaviruses, quercetin was identified as having potential for new drug development against the SARS coronavirus, as it interferes with an enzyme that is key to the viral life cycle in vitro (28). In human studies, quercetin (and other polyphenols) have a protective effect in smokers, lowering the odds of them getting lung cancer (29), and have also been suggested as a promising treatment for the common cold (30). Where can you find it? A plant compound, it is found in relatively low amounts in foods. Red onions, particularly the skins, are a source of quercetin - if you’re in the habit of making broth, put your onions in unpeeled. Grapes (and red wine) are another source, and raspberries, broccoli and black tea all contain some quercetin too (31). Supplementary quercetin is available in much greater quantities, and has a good safety profile (32); I would recommend talking to your healthcare provider before taking if you are on any medications. N-acetyl-cysteine (NAC) is an essential amino acid (a component of proteins) that plays a role in lung health. It is helpful in a couple of different ways: it can break up mucus, reduce inflammation, and serves as a precursor to glutathione (the most abundant antioxidant in the lungs). Studies have found that supplementation with NAC can decrease airway inflammation in asthma (33), reduce complications of bronchitis and COPD (34), and improve lung function in post-operative patients (35). That being said, there is no evidence of its effectiveness in the acute respiratory distress syndrome that we see in COVID-19 infection. Right now we can’t say whether it’s likely to be helpful for the current pandemic, but its benefits for general lung health and support of glutathione production makes it worth considering. Where can you find it? In food form, cysteine can be found in high protein foods like meats, fish, eggs, dairy products, lentils, seeds, and also onions (another reason to use them in stock). The supplementary form, NAC, can be found at health food stores and it has a relatively good safety profile. (That being said, consult with your health professional before taking if you are on any medications.) Melatonin is a hormone made in the brain that regulates sleep and wake cycles. It might seem a little out of place in a conversation about lung and immune health, but melatonin also acts as an anti-inflammatory and anti-oxidant. It has been shown to alleviate respiratory distress induced by viruses, bacteria and radiation, and authors of a recent paper suggest that it be considered in the treatment of COVID-19 on this basis (36). In other illnesses, melatonin supplementation has been convincingly shown to significantly reduce inflammatory cytokines (37). Perhaps by improving sleep, it allows the body to mount its own anti-inflammatory response. One other thing of note here is that melatonin levels tend to decrease as we age, with children having the highest levels and the elderly having the lowest (38). This could be a possible explanation for why children seem to be escaping relatively unscathed in the current pandemic, while the elderly are being hit the hardest (though this is likely multifactorial). Where can you find it? Many foods actually contain a little melatonin (e.g. eggs, milk, fish, grapes, tart cherries, tomatoes, peppers, pistachios and oats) (39). The amount of natural light that you’re exposed to during the day has a big influence on the production of melatonin at night, while blue light frequencies emitted from screens can interfere with melatonin production (40). To boost your melatonin without supplements, get outside during the day and steer clear of screens for a couple of hours before bedtime. References1. Hemila & Chalker (2007). Cochrane Database Syst Rev. (1):CD000980. doi: 10.1002/14651858.CD000980.pub4.
2. Hemilä (1999). Med Hypotheses. 1999 Feb;52(2):171-8. OI: 10.1054/mehy.1997.0639 3. Hemilä & Louhiala (2013). Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD005532. DOI: 10.1002/14651858.CD005532.pub3. 4. https://www.medicinenet.com/script/main/art.asp?articlekey=228745 5. Cascella, Rajnik, Cuomo, Dulebohn & Di Napoli (2020). https://www.ncbi.nlm.nih.gov/books/NBK554776/ 6. https://nypost.com/2020/03/24/new-york-hospitals-treating-coronavirus-patients-with-vitamin-c/ 7. Carr & Frei (1999). The American Journal of Clinical Nutrition, Volume 69, Issue 6, Pages 1086–1107, https://doi.org/10.1093/ajcn/69.6.1086 8. Cannell, Vieth, Umhau, Holick, Grant, Madronich, Garland & Giovannucci (2006). Epidemiol Infect. 2006 Dec;134(6):1129-40. Epub 2006 Sep 7. 9. Charan, Goyal, Saxena & Yadav (2012). J Pharmacol Pharmacother. 3(4):300-3. doi: 10.4103/0976-500X.103685. 10. Rondanelli, Miccono, Lamburghini, Avanzato, Riva, Allegrini, Faliva, Peroni, Nichetti & Perna (2018). Evidence-based complementary and alternative medicine : eCAM, 2018, 5813095. https://doi.org/10.1155/2018/5813095 11. https://www.bmj.com/content/368/bmj.m810/rr-36 12. Amrein, Papinutti, Mathew, Vila, & Parekh, (2018). Endocrine connections, 7(12), R304–R315. https://doi.org/10.1530/EC-18-0184 13. Christopher (2015). Curr Opin Clin Nutr Metab Care. 2015 Mar;18(2):187-92. doi: 10.1097/MCO.0000000000000147. 14. Forrest & Stuhldreher (2011). Nutr Res. 2011 Jan;31(1):48-54. doi: 10.1016/j.nutres.2010.12.001. 15. Haddad, Matsuoka, Hollis, Hu & Wortsman (1993). The Journal of clinical investigation, 91(6), 2552–2555. https://doi.org/10.1172/JCI116492 16. Black (2003). J Nutr. 133:1485S-9S. 17. Ervin & Kennedy-Stephenson (2002). J Nutr;132:3422-7. 18. Meydani, Barnett, Dallal, Fine, Jacques, Leka, et al. (2007). Am J Clin Nutr; 86:1167-73 19. Hulisz (2003). J Am Pharm Assoc. 2004;44:594-603 20. https://www.npr.org/sections/goatsandsoda/2020/03/26/821582951/is-loss-of-smell-and-taste-a-symptom-of-covid-19-doctors-want-to-find-out 21. Brown (1998). Am J Clin Nutr.; 68(suppl):425S–9S. 22. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2001. 23. Li, Yao, Han, Yang, Chaudry, Wang, Lui & Yin (2016). Nutrients.15;8(3):167. doi: 10.3390/nu8030167. 24. Davis, Murphy, McClellan, Carmichael & Gangemi (2008). Am J Physiol Regul Integr Comp Physiol. 295(2):R505-9. doi: 10.1152/ajpregu.90319.2008. 25. Wu, Li, Li, He, Jiang, Liu & Yang (2016). Viruses. 2016 Jan; 8(1): 6. doi: 10.3390/v8010006 26. Kim, Narayanan & Chang (2010). Antiviral Res. 2010 Nov;88(2):227-35. doi: 10.1016/j.antiviral.2010.08.016. 27. Kumar, Khanna, Srivastava, Tyagi, Raj & Ravi (2005). Exp Lung Res. 2005 Jun;31(5):449-59. 28. Chen, Li, Luo, Xu, Chen, Liew, Zhu, Puah, Shen & Jiang (2006). Bioorg Med Chem. 2006 Dec 15;14(24):8295-306 29. Woo, & Kim (2013). PloS one, 8(9), e75604. https://doi.org/10.1371/journal.pone.0075604 30. Kinker, Comstock & Sajjan (2014). J Anc Dis Prev Rem. 2 DOI: 10.4172/2329-8731.1000111 31. https://www.integrativepro.com/Resources/Integrative-Blog/2017/Quercetin-Food-Compared-Supplementation 32. Andres, Pevny, Ziegenhagen, Bakhiya, Schafer, Hirsch-Ernst & Lampen (2018). Mol Nutr Food Res. 62(1). doi: 10.1002/mnfr.201700447. 33. Lee, Hong & Jang (2020). Korean J Intern Med. doi: 10.3904/kjim.2019.105 34. Matera, Calzetta & Cazzola (2016). Expert Rev Respir Med. 10(1):89-97. doi: 10.1586/17476348.2016.1121105. 35. Li, Wei, Chen, Zhang, Liu, Hei & Yao (2018). Biosci Rep. 2018 Sep 28;38(5). pii: BSR20180858. doi: 10.1042/BSR20180858 36. Zhang, Wang, Ni et al. (2020). Life Sciences. https://doi.org/10.1016/j.lfs.2020.117583 37. Zarezadeh, Khorshidi, Emami, Janmohammadi, Kord-Varkaneh, Mousavi, Mohammed, Saedisomeolia & Alizadeh (2019). Eur. J. Nutr. (2019), 10.1007/s00394-019-02123-0 38. Waldhauser, Kovacs & Reiter (1998). Exp Gerontol. 33(7-8):759-72. 39. Meng, Li, Li, Zhou, Gan, Xu & Li (2017). Nutrients, 9(4), 367. https://doi.org/10.3390/nu9040367 40. https://www.health.harvard.edu/staying-healthy/blue-light-has-a-dark-side
3 Comments
Karen Stidston
3/29/2020 12:29:58 am
Thanks Amy. I found both articles very interesting and most informative.
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Amy Burkholder
3/30/2020 11:01:43 am
Thanks, Karen!
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AuthorHi, I'm Amy. I'm a nutritionist in the DC area, working with clients of all ages, focusing on prenatal and pediatrics. I'm all about straightforward, evidence-based health & wellness advice - because life/parenting in the modern world is complicated enough! Categories
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November 2022
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