Send response to journal:
Re: Can influenza vaccine overcome vitamin D deficiency?
 

Tom Jefferson points out that, for ethical reasons, it is difficult to conduct a truly random interventional study of influenza vaccine effectiveness. That is, given current recommendations, it is difficult for investigators to take a large group of well-matched elderly people, deny half of them a flu shot, and then wait to see who dies.

Another way to look at his argument is to ask if influenza related deaths have decreased in age groups most likely to be immunized (persons over age 65) more than in age groups less likely to be immunized (persons under age 65). If influenza vaccines are effective, then death rates should be falling over time in the heavily-vaccinated elderly but unchanged over time in lightly-vaccinated younger persons – all other things being equal.

In fact, influenza mortality and the influenza related hospitalization rates significantly increased for elderly Americans between 1980 and 2000, a phenomenon only partly explained by the aging population.(1,2) Increasing hospitalization and death rates among the elderly stands in stark contrast to annual mortality changes in persons less likely to be immunized. Excess pneumonia and influenza (P&I) deaths for persons under age 65 dramatically decreased between 1975 and 1994.(3) Childhood mortality rates due to all respiratory illnesses fell markedly in the 1990’s.(4)

If flu shots are effective - and if more older Americans have been getting them - why have more older Americans been dying of the flu? Furthermore, why has the P&I death rate in the younger - and less likely to be immunized - population declined so dramatically during this same time?

All other things being equal, such changes in P&I death rates are inconsistent with vaccine effectiveness, indeed they suggest the vaccine is dangerous. As is often the case in medicine, all other things are not equal.

Recently, in Epidemiology and Infection, my co-authors and I reviewed the substantial evidence that suggests vitamin D favorably affect influenza infection.(5) Indeed, the extant epidemiological and interventional evidence is so suggestive that we asked, “Is influenza infection a sign of vitamin D deficiency as much as Pneumocystis carinii pneumonia is a sign of AIDS.”

As 25(OH)D levels are dependent on surface UVB radiation, increased surface UVB radiation over time will tend to increase 25(OH)D levels over time. Surface UVB radiation, as inferred from satellite-based measurements, has increased since 1990, probably due to ozone depletion.(6)

Furthermore, the incidence of non-melanoma skin cancer, the skin cancer most closely associated with sunlight, dramatically increased in the 1980’s and 1990’s.(7,8) Likewise, cataracts are thought to be related to UVB radiation. Cataract extraction rates in Minnesota quadrupled between 1980 and 1992.(9)

Both the increasing incidence of non-melanoma skin cancers and increasing cataract extraction rates suggest that surface UVB radiation has significantly increased in the last 20 years. Increasing surface UVB should also increase average 25(OH)D levels, assuming no change in sun avoidance or global weather patterns. To my knowledge, no serial measurements of 25(OH)D levels in stored sera exist to confirm the hypothesis that increasing surface UVB radiation has translated into higher year-over-year 25(OH)D levels.

As surface UVB radiation increased, 25(OH)D levels would only have increased in those whose sun-exposure habits had either increased or not changed over time. Despite recent government campaigns to limit sun exposure, the young often ignore that advice while the elderly follow it.(10) Indeed, one estimate of sun exposure in the young actually showed it increased during the 1990’s.(11) That is, there are age- discrepant time trends in sun exposure habits over the last 20 years.

The vitamin D theory of influenza would predict that, despite influenza vaccines, P&I mortality among the elderly would have serially increased due to falling 25(OH)D levels, while P&I mortality among the young would have serially decreased due to increasing 25(OH)D levels. The age-discrepant time trends in P&I mortality that are being observed are exactly what the vitamin D theory of influenza would predict.

As Mr. Jefferson reported, "a messy blend of truth conflicts and conflicts of interest making it difficult to separate factual disputes from value disputes" in the debate about influenza vaccines. Perhaps the elderly, virtually all of whom are vitamin D deficient, would be better off getting an injection of vitamin D in the fall, rather than a flu shot?(12)

1. Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, et al. Influenza-associated hospitalizations in the United States. JAMA. 2004 Sep 15;292(11):1333-40.

2. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179-86.

3. Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, et al. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J Infect Dis. 1998;178:53-60.

4. Panickar JR, Dodd SR, Smyth RL, Couriel JM. Trends in deaths from respiratory illness in children in England and Wales from 1968 to 2000. Thorax. 2005;60:1035-8.

5. Cannell JJ, et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006 Dec;134(6):1129-40. Epub 2006 Sep 7.

6. Pinker RT, Zhang B, Dutton EG. Do satellites detect trends in surface solar radiation? Science. 2005;308:850-4.

7. Christenson LJ, Borrowman TA, Vachon CM, Tollefson MM, Otley CC, et al., Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005;294:681-90.

8. Karagas MR, Greenberg ER, Spencer SK, Stukel TA, Mott LA. Increase in incidence rates of basal cell and squamous cell skin cancer in New Hampshire, USA. New Hampshire Skin Cancer Study Group. Int J Cancer. 1999 May 17;81(4):555-9.

9. Baratz KH, Gray DT, Hodge DO, Butterfield LC, Ilstrup DM. Cataract extraction rates in Olmsted County, Minnesota, 1980 through 1994. Arch Ophthalmol. 1997 Nov;115(11):1441-6.

10. Stoebner-Delbarre A, Thezenas S, Kuntz C, Nguyen C, Giordanella JP, et al. [Sun exposure and sun protection behavior and attitudes among the French population] Ann Dermatol Venereol. 2005;132:652-7. (abstract only)

11. Robinson JK, Rigel DS, Amonette RA. Trends in sun exposure knowledge, attitudes, and behaviors: 1986 to 1996. J Am Acad Dermatol. 1997;37:179-86.

12. Kaplan M. Sunshine may beat the winter flus. Seasonal illnesses could be down to lack of vitamin D. Nature. 3 November 2006; | doi:10.1038/news061030-12