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Vitamins and Infrastructure do the Work; Vaccines get the Credit: Critique of Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland, BMJ 2019

The PDF version is considered the final version and is located at

Inaccurate attribution of efficacy to vaccination: British Medical Journal (BMJ) published a retrospective study crediting vaccination against human papilloma virus (HPV) with reduction in HPV prevalence in Scotland[1], and as usual with positive pharmaceutical news, this study was published in headlining news outlets such as The Guardian[2] thereby influencing the opinions of hundreds of thousands and potentially millions of patients, physicians, and politicians. Retrospective studies cannot establish causation but can suggest correlation, but only if other influential variables are considered and excluded as causal or contributory. In the current situation, the authors failed to account for public health measures that have higher levels of evidence including double-blind placebo-controlled trials than does the HPV vaccination, which has never been the subject of a valid double-blind placebo-controlled trial with a true placebo. In this rebuttal, I show that their conclusion—“Routine vaccination of girls aged 12-13 years with the bivalent HPV vaccine in Scotland has led to a dramatic reduction in preinvasive cervical disease. Evidence of clinically relevant herd protection is apparent in unvaccinated women. These data are consistent with the reduced prevalence of high risk HPV in Scotland. The bivalent vaccine is confirmed as being highly effective vaccine and should greatly reduce the incidence of cervical cancer.”—is unsubstantiated. Remarkably, the entire document fails to mention the words “vitamin”, “nutrition” or “cholecalciferol” despite the facts that the Scottish Government recognized the high prevalence of vitamin D3 in its population and began recommending vitamin D3 supplementation in 2009, coincident with the HPV vaccination campaign in 2008.


Vitamin D paradigm shifts and increased usage: Our views of vitamin D3 (cholecalciferol) began to experience a complete paradigm shift that was well under way in the early part of this century with landmark publications such as Vieth’s dogma-overturning 1999 “Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety” in American Journal of Clinical Nutrition[3], Zittermann’s 2003 “Vitamin D in preventive medicine” in British Journal of Nutrition[4], and Vasquez’s 2004 “The clinical importance of vitamin D (cholecalciferol): a paradigm shift with implications for all healthcare providers” in Alternative Therapies in Health and Medicine[5] followed by an important partial summary in British Medical Journal the following year.[6] These and similarly themed articles in the peer-reviewed research have contributed to increased awareness of vitamin D3’s safety and roles in preventive medicine and public health, including preventing infectious diseases such as viral infections and various types of cancer. Consistent with this evidence of safety and benefit, along with evidence that the human daily requirement is an order of magnitude greater than previously believed[7], use of vitamin D3 supplementation began to increase slowly and then exponentially in the United States[8] and presumably other countries, especially English-speaking societies, most notably the United Kingdom.


Widespread vitamin D deficiency in Scotland, followed by widespread recommendations for vitamin D supplementation starting in 2009: Deficiency of vitamin D3 would be expected in the United Kingdom given its far northern latitude which reduces dermal production of cholecalciferol along with the cold and rainy climate that encourages use of full-length shirts, pants, and coats and structural protection from the weather and hence sun exposure. In 2006, Burleigh and Potter published in Scottish Medical Journal[9] stating that, “The prevalence of vitamin D deficiency is high in older outpatients in this geographical area. These patients may benefit from routine vitamin D and calcium, but currently many would not be targeted in recent Scottish Executive recommendations because they are not housebound and sunlight deprived.” In 2007, Hyppönen and Power[10] showed that among British adults “Prevalence of hypovitaminosis D in the general population was alarmingly high during the winter and spring, which warrants action at a population level rather than at a risk group level.” In 2008, Rhein[11] further specified that “Vitamin D deficiency is widespread in Scotland”. In 2009, the Scottish Government acknowledged the need to educate its population about the importance of vitamin D3 supplementation.[12] From that time until the present, the Scottish Government, United Kingdom National Health Services, and various advocacy groups and programs (e.g.,[13], Healthy Start, which provides vitamin D supplements to all children and pregnant women in Scotland[14]) continue assertive public health campaigns recommending vitamin D3 supplementation and increased vitamin D production via sun exposure via the “Shine on Scotland” program initiated in 2009[15] for all of its citizens.[16],[17],[18],[19],[20]


Vitamin D supplementation provides antiinflammatory, antiviral, and anticancer benefits: Unlike the HPV vaccine, vitamin D supplementation has been the subject of many high-quality placebo-controlled trials. According to human clinical trials, vitamin D supplementation and correction of vitamin D deficiency has shown significant antiinflammatory[21] and immunomodulatory[22] benefits. Vitamin D and its direct metabolites promote production of antimicrobial peptides which have antibacterial and antiviral properties, while also reducing viral replication generally by inhibiting the NF-kappaB pathway used for viral replication. In 2017, Vahedpoor and colleagues[23] published “Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial” in the peer-reviewed journal Hormones and Cancer in which they concluded, “In conclusion, vitamin D3 administration for 6 months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels.” In 2018, Vahedpoor and colleagues[24] published “Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial” in the peer-reviewed journal Annals of Nutrition and Metabolism in which they concluded, “Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.”


Vitamin D supplementation in Scotland has a stronger evidence base—as well as lower cost, greater safety, and more collateral benefits—compared to HPV vaccination: In Scotland, programs advocating HPV vaccination and vitamin D supplementation occurred at the same time. Crediting the reduction in HPV-related disease to vaccination via retrospective population study is invalid and misleading, especially when the authors make no mention whatsoever of the national program for vitamin D supplementation which started in the same timeframe. The quality of evidence supporting safety, efficacy, collateral benefits, affordability and availability all favor vitamin D supplementation over HPV vaccination.


Dr Vasquez is an international expert in nutrition, integrative/functional medicine, neuroinflammation, microbiology and dysbiosis; he is the author of numerous books and articles, including Brain Inflammation in Migraine and Fibromyalgia (2016), Mitochondrial Nutrition and Endoplasmic Reticulum Stress in Primary Care, 2nd Edition (2014), Antiviral Strategies and Immune Nutrition (2014), Mastering mTOR (2015), Autism, Dysbiosis, and the Gut-Brain Axis (2017) and the 1200-page Inflammation Mastery 4th Edition (2016) also published as a two-volume set titled Textbook of Clinical Nutrition and Functional Medicine. DrV has served as a consultant researcher for Biotics Research Corporation.


[1] Palmer T, Wallace L, Pollock KG, Cuschieri K, Robertson C, Kavanagh K, Cruickshank M. Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study. BMJ. 2019 Apr 3;365:l1161. doi: 10.1136/bmj.l1161

[2] Boseley S. HPV rates tumble after routine vaccination. Guardian 2019 Apr

[3] Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56

[4] Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr. 2003 May;89(5):552-72

[5] Vasquez A, Manso G, Cannell J. The clinical importance of vitamin D (cholecalciferol): a paradigm shift with implications for all healthcare providers. Altern Ther Health Med. 2004 Sep-Oct;10(5):28-36

[6] Vasquez A, Cannell J. Calcium and vitamin D in preventing fractures: data are not sufficient to show inefficacy. BMJ. 2005 Jul 9;331(7508):108-9

[7] Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003 Jan;77(1):204-10

[8] Rooney MR, Harnack L, Michos ED, Ogilvie RP, Sempos CT, Lutsey PL. Trends in Use of High-Dose Vitamin D Supplements Exceeding 1000 or 4000 International Units Daily, 1999-2014. JAMA. 2017 Jun 20;317(23):2448-2450. doi: 10.1001/jama.2017.4392

[9] Burleigh E, Potter J. Vitamin D deficiency in outpatients: a Scottish perspective. Scott Med J. 2006 May;51(2):27-31

[10] Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007 Mar;85(3):860-8

[11] Rhein HM. Vitamin D deficiency is widespread in Scotland. BMJ. 2008 Jun 28;336(7659):1451. doi: 10.1136/bmj.39619.479155.3A

[12] Boy wins NHS backing in vitamin D campaign. The Scotsman 2009 December Accessed April 2019

[13] “At, we believe the people of Scotland would see health improvements by taking a regular Vitamin D supplement. We think there is enough evidence currently available to make all of us take action, from health care professionals to parents and teachers.” Accessed April 2019

[14] "The United Kingdom National Health Services created a program called Healthy Start, which offers vouchers for free vitamin D supplements to qualifying pregnant women, women with a baby under one year old and children under the age of five years located in Scotland, Northern Ireland, England and Wales. In April of 2017, the Scottish government partnered with the Healthy Start program to offer free vitamin D supplements to all Scottish pregnant women, regardless of whether they qualify for vouchers. This joint effort was created to decrease the risk of rickets and other health complications caused by vitamin D deficiency. Scotland offers free vitamin D supplements for all pregnant residents. Posted on: November 28, 2017   by  Missy Sturges & John Canell, MD. See also: National Health Services Scotland. Vitamin D. Accessed April 2019

[15] Scottish warning over vitamin D levels. 19 September 2010 Accessed April 2019

[16] "Following recommendations from the Scientific Advisory Committee on Nutrition (SACN), Scottish Government advice on vitamin D for all age groups has been updated as follows: Everyone age 5 years and above should consider taking a daily supplement of 10 micrograms vitamin D, particularly during the winter months (October – March)." Scottish Government. Vitamin D.  Accessed April 2019

[17] Scottish Government. Vitamin D information for health professionals in Scotland. November 2017 Accessed April 2019

[18] "Scots should consider taking vitamin D supplements all-year round, but particularly in autumn and winter, according to new health advice." All Scots advised to take vitamin D says new health guidance. 21 July 2016. Accessed April 2019

[19] "International experts are calling for food in Scotland to be fortified with vitamin D, in an attempt to cut the large numbers of people who develop multiple sclerosis at sunshine-deprived northern latitudes." Add vitamin D to Scotland's food – experts: Dosing whole population would help cut levels of multiple sclerosis, say scientists. 23 Dec 2011 Accessed April 2019

[20] All Scottish babies should have vitamin D supplement, CMO says. The Pharmaceutical Journal 2017 Nov 30. Accessed April 2019

[21] Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D, Aganna E, Price CP, Boucher BJ. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM. 2002 Dec;95(12):787-96

[22] Luthold RV, Fernandes GR, Franco-de-Moraes AC, Folchetti LG, Ferreira SR. Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals. Metabolism. 2017 Apr;69:76-86. doi: 10.1016/j.metabol.2017.01.007. Epub 2017 Jan 13.

[23] Vahedpoor Z, Jamilian M, Bahmani F, Aghadavod E, Karamali M, Kashanian M, Asemi Z. Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial. Horm Cancer. 2017 Feb;8(1):58-67. doi: 10.1007/s12672-016-0278-x. Epub 2017 Jan 3

[24] Vahedpoor Z, Mahmoodi S, Samimi M, Gilasi HR, Bahmani F, Soltani A, Sharifi Esfahani M, Asemi Z. Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Nutr Metab. 2018;72(2):151-160. doi: 10.1159/000487270. Epub 2018 Feb 21.

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