James B. LaValle, RPh, CCN, MT, ND(trad), is an internationally recognized clinical pharmacist, author, board certified clinical nutritionist and naturopathic doctorate with more than 35 years of clinical experience. In addition to his LaValle Metabolix Practice he works with players and teams from the NFL, NBA, MLB, MLS, NHL and is the Clinical Director of the Hall of Fame Performance Health Program. He is best known for his expertise in metabolic and integrative medicine, with an extensive background in natural products, lifestyle drug/nutrient depletion and uncovering the underlying metabolic issues that keep people from feeling healthy and vital. LaValle is an appointed faculty member and course educator for the Integrative Medicine postgraduate program at George Washington University School of health sciences. He is author of more than 22 books including, Your Blood Never Lies, and serves as a scientific adviser for the Organic & Natural Health Assocation. His cloud-based laboratory assessment system can be reviewed at http://metaboliccode.com/. (Altern Ther Health Med. 2020;26(S2):46-48)
Introduction
The recent global outbreak of COVID-19 has inflicted devastating impact around the world, specifically among elderly and chronically ill populations. Currently, no treatment or vaccine against the virus is available. Consequently, there is a significant need to search for potential therapeutic approaches that can reduce the number of severe COVID-19 cases and thus reduce the mortality rate associated with the disease.
The objective of this article is to inform and educate the healthcare professional about vitamin D, the science behind its immune function and its potential beneficial effects on COVID-19 patients. Vitamin D is an important supplement in the practitioner’s therapeutic arsenal.
Background
All clinicians have studied what vitamin D is and the benefits are in the human body. We learned that vitamin D supports immunity, but do we understand how important this single hormone/nutrient can be for protecting the lives of our patients in everyday life, especially during times such as these – the COVID-19 pandemic? Let’s look at some of the potential causes of low levels of vitamin D and how adequate levels can support public health during a pandemic.
Depleted Vitamin D
Currently more than 1 billion people worldwide are considered vitamin D deficient (< 20 ng/ml) and nearly half of all Americans are vitamin D deficient.1 Age, season, northern latitudes, liver and kidney function, obesity/overweight, poor dietary intake, dark skin tone and certain medications (see below) all contribute to low vitamin D levels.
Vitamin D3 deficiency is linked to chronic health conditions including:2
- Obesity
- Diabetes, insulin resistance
- Hypertension and other cardiovascular issues
- Depression
- Fibromyalgia,
- Chronic fatigue syndrome
- Osteoporosis
- Neuro-degenerative diseases including Alzheimer’s disease.
- Cancers, especially breast, prostate, and colon cancers.
The following drugs can cause a depletion of vitamin D, which may increase an individual’s need for vitamin D:3
- Anticonvulsants: barbiturates, carbamazepine, fosphenytoin and phenytoin
- Cholesterol lowering drugs: statins (Lipitor, Mevacor, Lescol, Pravachol, Zocor) and Bile acid sequestrants (cholestyramine and colestipol) and fibrates (Tricor, Lopid/gemfibrazole)
- Corticosteroids: prednisone (Decadron), cortisone, hydrocortisone, methylprednisolone
- H-2 receptor antagonists: Tagamet, Zantac, Pepcid and Axid
- Proton-pump inhibitors: Prevacid, Protonic, Zegerid, Prilosec and Nexium
- Mineral oil
- Isoniazid
- Rifampin
- Orlistat (Xenical)
Vitamin D in COVID-19 Patients
The beneficial effects of vitamin D on protective immunity from COVID-19 and other viruses are due in part to its effects on the innate immune system.4 Vitamin D has immunomodulatory properties that include downregulation of pro‐inflammatory cytokines. In vitro data reports that in addition to modulating innate immune cells, vitamin D also promotes a more “tolerant” immunological status.5 Importantly in our current pandemic situation, studies report vitamin D attenuates lipopolysaccharide‐induced acute lung injury in mice by blocking effects on the angiopoietin (Ang)‐2‐Tie‐2 signaling pathway and on the renin‐angiotensin pathway.6 Vitamin D is also reported to increase the antiviral activity of bronchial epithelial cells in laboratory studies.7
There have been multiple cross-sectional studies associating lower levels of vitamin D with increased respiratory infections.
- One study in 19 000 subjects between 1988 and 1994 reported individuals with lower vitamin D levels (<30 ng/ml) were more likely to self-report a recent upper respiratory tract infection than those with sufficient levels, even after adjusting for variables including season, age, gender, body mass and race.8
- Another cross-sectional study of 800 military recruits in Finland stratified men by serum vitamin D levels reported those with lower vitamin D levels lost significantly more days from active duty secondary to upper respiratory infections than recruits with higher vitamin D levels.9
- A 2017 systematic review and meta-analysis published in the BMJ, looked at vitamin D supplementation in 25 randomized trials and over 11 300 participants in preventing acute respiratory tract infections. The authors concluded vitamin D supplementation was safe and it protected against acute respiratory tract infection overall.10
- There have been a number of other cross-sectional studies looking at vitamin D levels and rates of influenza11 as well as other infections including bacterial vaginosis and HIV.12,13 All have reported an association of lower vitamin D levels and increased rates of infection.
- In 2017, a large analysis of prospective clinical trials reported that taking vitamin D reduces the odds of developing a respiratory infection by approximately 42% in people with low baseline levels of 25-hydroxyvitamin D below 25 ng/mL.14
And more recent studies of vitamin D in COVID-19 patients include:
- COVID-19 patients with severe vitamin D deficiency are twice as likely to experience major complications than those not infected.15
- COVID-19 has a mortality rate that is currently higher in Northern latitudes, with Italy the highest (11.9%). Deaths and hospitalizations have to date occurred in 5.2% and 22% of patients in Northern latitudes; in 3.1% and 9.5% close to the Equator; and in 0.7% and 8.7% in Southern latitudes, respectively – pointing to a direct correlation with vitamin D levels and mortality in Northern populations with inherently lower vitamin D levels.16
- In a 2020 study that has not been peer reviewed, researchers analyzed patient data from 10 countries and found a direct correlation between low vitamin D levels and hyperactive immune systems, creating the “cytokine storm” and increasing mortality in vulnerable patients.17 This research suggests adequate vitamin D levels may cut the mortality rate in half.
- Researchers at Medical University of South Carolina (MUSC) College of Medicine, led by world-renowned vitamin D research experts Dr. Bruce Hollis, PhD, are currently performing focused research in an effort to determine if individuals with sufficient baseline levels of vitamin D have more protection against severe COVID-19 infection.18
Testing and Dosing Vitamin D
All patients should have adequate vitamin D levels, not only for bone, cardiovascular, neurological and metabolic health, but for immune support during COVID-19 pandemic. Patients should be tested for vitamin D levels (which can be done at home with in-home testing kits).
Vitamin D testing should analyze TOTAL vitamin D levels in the body, which includes Vitamin D2 (ergocalciferol) and D3 (cholecalciferol). According to Cannel et al, 2006, total vitamin D levels of 50 ng/ml and greater appear to protect against viral respiratory infection.19
Total vitamin D levels are trending low at 20-50 ng/ml and at low less than 20 ng/ml.
If levels are between 20 and 50ng/ml, consider using:
- Vitamin D3, 5 000 IU (125 mcg) daily
If levels are less than 20ng/ml, consider using:
- Vitamin D3, 10 000 IU (250 mcg) daily for 2-3 months, then recheck.
Adults who are vitamin D deficient who are at high risk because of being obese, taking certain medications, having a malabsorption syndrome or identifying as African American or Hispanic are recommended to take at least 10 000 IU daily. Vitamin D calculators are available that can help in getting correct dosages of vitamin D3 supplementation, such as the one offered by Organic & Natural Health Association at http://www.nutrientpower.org/.
Supplementing vitamin D3 doses with vitamin K2 (menaquinone) is a good idea, although if you recommend a proper diet, enough K2 is consumed. There’s a reported synergistic relationship between the two for bone health and cardiovascular health.20 In general 100 mcg vitamin K2 as menaquinone is sufficient.
Note this article is part of a forum for sharing information concerning the practical use of alternative, complementary and cross-cultural therapies in preventing and treating disease, healing illness and promoting health. It encourages the integration of alternative therapies with conventional medical practices in a way that provides for a rational, individualized, comprehensive approach to healthcare. This article is not meant to diagnose or treat any disease or illness and is for educational purposes only.
References
- Parva NR, et al. Prevalence of vitamin D deficiency and associated risk factors in the US population (2011-2012). Cureus. 2018;10(6):e2741.
- Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86(1).50-60.
- Lavalle JB, Pelton R, Hawkins EB. Drug-Induced Nutrient Depletion Handbook, 2001. LexiComp Publishing, Hudson OH.
- Aranow C. Vitamin D and the Immune system. J Investig Med. 2011;59(6):881-86.
- Prietl B, et al. Vitamin D and immune function. Nutrients. 2013;5(7):2502-21.
- Arboleda JF, et alo. Vitamin D mediated attenuation of miR-155 in human macrophages in jected with dengue virus: Implications for the cytokine respoinse. Infect Genert Evol. 2019;69:12-21.
- Telcian AG, et al. Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro. Antiviral Res. 2017;137:L93-101.
- Ginde AA, Mansbach JM, Camargo CA., Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384–90.
- Laaksi I, et al. An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. 2007;86(3):714–7.
- Martineau AR, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
- Cannell JJ, et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006;134(6):1129–40.
- Rodriguez M, et al. High frequency of vitamin D deficiency in ambulatory HIV-Positive patients. AIDS Res Hum Retroviruses. 2009;25(1):9–14.
- Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr. 2009;139(6):1157–61.
- Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. 2017;356:i6583.
- Daneshkhah A, et al The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. MedRxiv. https://doi.org/10.1101/2020.04.08.20058578.
- Panarese A. Letter: Covid-19 and vitamin D. Aliment Pharmacol Therap. 2020;51(10): https://doi.org/10.1111/apt.15752.
- Daneshkhah A, et al The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. MedRxiv. https://doi.org/10.1101/2020.04.08.20058578
- https://web.musc.edu/about/leadership/institutional-offices/communications/pamr/news-releases/2020/musc-world-class-vitamin-d-research-team-to-study-connection-to-covid-19-prevention-and-treatment. Accessed May 2020.
- Cannel JJ, et al. Epidemic Influenza and vitamin D. Epidemiol Infect. 2006;134(6):1129-40.
- vanBallegooijen AJ, et al. The synergistic interplay between vitamin D and K for bone and cardiovascular health: a narrative review. Int J Endocrinol. 2017;2017:74543786.