Vitamin D could reduce case fatality rates during an influenza pandemic
William B. Grant, Sunlight, Nutrition and Health Research Center (SUNARC)
5 August 2009
The recent paper on use of antivirals during an influenza pandemic suggests that priority for antiviral use during influenza pandemics be given to younger people since in the 1918-1919 influenza pandemic, mortality rates were much higher among the young than the elderly [1]. This was the case in Denmark [2] as well as the United States [3]. The reason for the disparity with respect to age may be that the elderly have antibodies for such viruses based on exposure to similar viruses earlier in life [4].
Use of antivirals is generally limited to, perhaps, 25% of the population due to cost considerations. However, there is another, inexpensive approach to reducing case-fatality rates during an influenza pandemic, raising serum 25-hydroxyvitamin D [25(OH)D] levels of the population. Vitamin D was hypothesized to reduce the risk of seasonal influenza in paper in 2006 [5]. The proposed mechanism was induction of human cathelicidin, LL-37, which has both antimicrobial and antiendotoxin effects [6]. A post-hoc analysis of influenza and rhinovirus cases during a randomized controlled trial of vitamin D supplementation found that those taking 800 IU/day of vitamin D had a 60% reduction and those taking 2000 IU/day had a 90% reduction in cases [7]. While there is no evidence that vitamin D reduces the risk of influenza pandemic infection, there is evidence that vitamin D reduces case-fatality rates. In an ecological analysis of case fatality rates in 12 U.S. cities during the 1918-1919 influenza pandemic using summertime and wintertime solar ultraviolet-B (UVB) indices, high inverse correlations were found (for case fatality rate with respect to July UVB, r = -0.72; for pneumonia as a complication of influenza with respect to July UVB, r = -0.77) [8]. The proposed mechanisms were reduction of the cytokine storm by 1,25-dihydroxyvitamin D and reduction of bacterial pneumonia by cathelicidin. Increasing serum 25(OH)D levels from population mean values of 20-30 ng/mL to 40-60 ng/mL should greatly reduce the case-fatality rate during an influenza pandemic. Such increases could be made with large doses (50,000 IU/day) for a short period, followed by daily doses of about 4000 IU/day [9]. Long-term vitamin D doses of 10,000 IU/day are considered safe for most people [10]. There are many other health benefits of vitamin D [11], so increasing serum 25(OH)D levels at the population level would have many additional benefits [12].
References 1. Merler S, Ajelli M, Rizzo C: Age-prioritized use of antivirals during an influenza pandemic. BMC Infectious Diseases 2009, 9:117
2. Andreasen V, Viboud C, Simonsen L: Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies. Journal of Infectious Diseases 2008, 197(2):270–278.
3. Britten RH. The incidence of epidemic influenza, 1918–19. Public Health Reports 1932, 47:303-339.
4. Yu X, Tsibane T, McGraw PA, House FS, Keefer CJ, Hicar MD, Tumpey TM, Pappas C, Perrone LA, Martinez O, Stevens J, Wilson IA, Aguilar PV, Altschuler EL, Basler CF, Crowe JE Jr. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 2008, 455(7212):532-536.
5. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiology and Infection 2006, 134(6):1129-1140.
6. Mookherjee N, Rehaume LM, Hancock RE. Cathelicidins and functional analogues as antisepsis molecules. Expert Opininion on Therapeutic Targets 2007, 11(8):993-1004.
7. Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin D. Epidemiology and Infection 2007, 135(7):1095-1096; author reply 1097-1098.
8. Grant WB, Giovannucci E. The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918–1919 influenza pandemic in the United States. Dermato-Endocrinology 2009, 1(4) epub
9. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. American Journal of Clinical Nutrition 2003, 77(1):204-210.
10. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. American Journal of Clinical Nutrition 2007, 85(1):6-18.
11. Holick MF. Vitamin D deficiency. New England Journal of Medicine 2007, 357(3):266-281.
12. Grant WB, Cross HS, Garland CF, Gorham ED, Moan J, Peterlik M, Porojnicu AC, Reichrath J, Zittermann A. Estimated benefit of increased vitamin D status in reducing the economic burden of disease in Western Europe. Progress in Biophysics and Molecular Biology 2009 Mar 3. [Epub ahead of print]
Competing interests
Disclosure I receive funding from the UV Foundation (McLean, VA), the Vitamin D Society (Canada), and the European Sunlight Association (Brussels).
Vitamin D could reduce case fatality rates during an influenza pandemic
5 August 2009
The recent paper on use of antivirals during an influenza pandemic suggests that priority for antiviral use during influenza pandemics be given to younger people since in the 1918-1919 influenza pandemic, mortality rates were much higher among the young than the elderly [1]. This was the case in Denmark [2] as well as the United States [3]. The reason for the disparity with respect to age may be that the elderly have antibodies for such viruses based on exposure to similar viruses earlier in life [4].
Use of antivirals is generally limited to, perhaps, 25% of the population due to cost considerations. However, there is another, inexpensive approach to reducing case-fatality rates during an influenza pandemic, raising serum 25-hydroxyvitamin D [25(OH)D] levels of the population. Vitamin D was hypothesized to reduce the risk of seasonal influenza in paper in 2006 [5]. The proposed mechanism was induction of human cathelicidin, LL-37, which has both antimicrobial and antiendotoxin effects [6]. A post-hoc analysis of influenza and rhinovirus cases during a randomized controlled trial of vitamin D supplementation found that those taking 800 IU/day of vitamin D had a 60% reduction and those taking 2000 IU/day had a 90% reduction in cases [7]. While there is no evidence that vitamin D reduces the risk of influenza pandemic infection, there is evidence that vitamin D reduces case-fatality rates. In an ecological analysis of case fatality rates in 12 U.S. cities during the 1918-1919 influenza pandemic using summertime and wintertime solar ultraviolet-B (UVB) indices, high inverse correlations were found (for case fatality rate with respect to July UVB, r = -0.72; for pneumonia as a complication of influenza with respect to July UVB, r = -0.77) [8]. The proposed mechanisms were reduction of the cytokine storm by 1,25-dihydroxyvitamin D and reduction of bacterial pneumonia by cathelicidin. Increasing serum 25(OH)D levels from population mean values of 20-30 ng/mL to 40-60 ng/mL should greatly reduce the case-fatality rate during an influenza pandemic. Such increases could be made with large doses (50,000 IU/day) for a short period, followed by daily doses of about 4000 IU/day [9]. Long-term vitamin D doses of 10,000 IU/day are considered safe for most people [10]. There are many other health benefits of vitamin D [11], so increasing serum 25(OH)D levels at the population level would have many additional benefits [12].
References
1. Merler S, Ajelli M, Rizzo C: Age-prioritized use of antivirals during an influenza pandemic. BMC Infectious Diseases 2009, 9:117
2. Andreasen V, Viboud C, Simonsen L: Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies. Journal of Infectious Diseases 2008, 197(2):270–278.
3. Britten RH. The incidence of epidemic influenza, 1918–19. Public Health Reports 1932, 47:303-339.
4. Yu X, Tsibane T, McGraw PA, House FS, Keefer CJ, Hicar MD, Tumpey TM, Pappas C, Perrone LA, Martinez O, Stevens J, Wilson IA, Aguilar PV, Altschuler EL, Basler CF, Crowe JE Jr. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 2008, 455(7212):532-536.
5. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiology and Infection 2006, 134(6):1129-1140.
6. Mookherjee N, Rehaume LM, Hancock RE. Cathelicidins and functional analogues as antisepsis molecules. Expert Opininion on Therapeutic Targets 2007, 11(8):993-1004.
7. Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin D. Epidemiology and Infection 2007, 135(7):1095-1096; author reply 1097-1098.
8. Grant WB, Giovannucci E. The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918–1919 influenza pandemic in the United States. Dermato-Endocrinology 2009, 1(4) epub
9. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. American Journal of Clinical Nutrition 2003, 77(1):204-210.
10. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. American Journal of Clinical Nutrition 2007, 85(1):6-18.
11. Holick MF. Vitamin D deficiency. New England Journal of Medicine 2007, 357(3):266-281.
12. Grant WB, Cross HS, Garland CF, Gorham ED, Moan J, Peterlik M, Porojnicu AC, Reichrath J, Zittermann A. Estimated benefit of increased vitamin D status in reducing the economic burden of disease in Western Europe. Progress in Biophysics and Molecular Biology 2009 Mar 3. [Epub ahead of print]
Competing interests
Disclosure
I receive funding from the UV Foundation (McLean, VA), the Vitamin D Society (Canada), and the European Sunlight Association (Brussels).