Vitamins Against Viruses (2)

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By Alex Vasquez

The text of my rapid response to the Editorial posted on BMJ.com is as follows:

“Scotland’s public health programs and trends improving nutritional status should be considered when discussing HPV trends

Julia Brotherton’s Editorial accompanying the retrospective population study crediting vaccination against human papilloma virus (HPV) with reduction in HPV prevalence in Scotland considers a variety of possibilities for the presumed success of the HPV vaccination program. However, her Editorial does not mention the concomitant public health programs organized by the Scottish Government and other groups to improve vitamin D nutriture throughout Scotland that occurred in the same time-frame.

The Scottish Government recognized the high prevalence of vitamin D deficiency in its population and began recommending vitamin D supplementation not later than 2006. By 2009, coincident with the start of the HPV vaccination campaign in 2008, numerous vitamin D supplementation (and sun exposure) campaigns were being implemented throughout Scotland to combat the documented population-wide problem of vitamin D deficiency.

Our views of vitamin D experienced a paradigm shift in the early part of this century, with key publications starting in 1999. We now have increased awareness of vitamin D’s safety and roles in preventive medicine and public health, including reducing the burden of infectious diseases such as viral infections. 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, use of vitamin D supplementation began to increase slowly and then exponentially in the United States and other countries, especially English-speaking societies, most notably the United Kingdom.

Indeed, according to the Scottish Health Survey 2003, use of dietary supplements such as vitamins (including vitamin D), fish oils (a source of vitamin D) and minerals (magnesium supplementation improves vitamin D status and is necessary for vitamin D activation, binding, transport, metabolism, and gene expression) had already begun to increase between 1998 and 2003. Certainly not later than 2006, the Scottish Government was already recommending widespread use of vitamin D supplements (and sun exposure) to combat the high prevalence of vitamin D deficiency in Scotland.

Vitamin D supplementation has been the subject of several placebo-controlled trials documenting anti-inflammatory, antiviral, and anticancer effects. Correction of vitamin D deficiency has significant anti-inflammatory and immunomodulatory benefits. Vitamin D and its direct metabolites promote production of antimicrobial peptides which have antibacterial and antiviral properties, while also reducing viral replication by inhibiting the NF-kappaB pathway.

Consistent with these immunomodulatory and antiviral mechanisms, data from several placebo-controlled trials shows that vitamin D provides benefit in a variety of infectious conditions including human immunodeficiency virus (HIV), hepatitis C virus and upper respiratory infections. Vitamin D administration displays impressive clinical effectiveness against dermal HPV as shown in case reports, clinical series, and placebo-controlled trials, with remarkable safety, high efficacy, and a consistent trend toward complete resolution of lesions.

In 2014, Schulte-Uebbing et al published ‘Chronical cervical infections and dysplasia (CIN I, CIN II): vaginal vitamin D (high dose) treatment’ showing that among 200 women with cervical dysplasia, vitamin D vaginal suppositories (12,500 IU, 3 nights per week, for 6 weeks) provided ‘very good anti-inflammatory effects’ and ‘good antidysplastic effects’ in women with CIN 1. In 2017, Vahedpoor and colleagues published ‘Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia’ in which they summarized, ‘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 published ‘Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3’ in which they noted, ‘The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively’, thereby clearly favoring treatment with vitamin D over placebo.

In Scotland, programs advocating HPV vaccination (started in 2008) and vitamin D supplementation (started not later than 2006 and again in 2009) occurred in close chronologic proximity; use of nutritional supplements that contain or potentiate vitamin D had started to increase in the population by 2003. Crediting the reduction in HPV-related disease solely to vaccination via retrospective population study is potentially misleading, especially when these authors make no account whatsoever of the national program for vitamin D supplementation which started in the same time-frame. Numerous studies have shown that vitamin D provides immunomodulatory, anti-inflammatory, microbiome-modifying, antiviral and anti-HPV benefits with high safety, good efficacy, low cost, wide availability, and clinically important collateral benefits.”

Following the posting of my rapid response critiquing the editorial (11 Apr 2019), BMJ posted my resubmitted response rebutting the original research two days later (13 Apr 2019).

Some but not all of the problems with the editorial are also noted in and originate from the primary research and therefore my critiques are similar, but not identical, with the second response a bit more refined and also with changes in a few citations.

The major errors in the primary article are as follows: First, the study design of ‘retrospective population study’ is incapable of determining causal relationships; at best such a study design can only determine temporal relationships, i.e., two events occurring together within the same time-period or one event following the other. As such, their reporting of any causal relationship is erroneous because this type of study cannot establish causality. Subsequently, the editorial and mass media derivatives are likewise erroneous.

Second, attribution of effectiveness to the vaccine while ignoring any and all education surrounding the vaccine conflates inoculation with behavior-modifying education. Telling a young girl in essence that ‘the vaccination is directed toward a sexually transmitted infection in the form of a virus that could infect her vagina and cervix if she has unprotected sex with a boy’ is a behavior-changing conversation likely to reduce sexual intercourse, with boys, especially without barrier protection; this primary study by Palmer and colleagues completely failed to account for any effect of education, instead giving all credit – indeed premature and inappropriate credit – to the vaccine.

The age correlation that they reported – less HPV with earlier vaccination – could easily be explained or confounded with earlier education that changes sexual behavior. The authors failed to consider anything other than vaccination, so of course they found a correlation between vaccination and reduced HPV-related disorders.

Third, the authors ascribe ‘herd immunity’ to the observation that unvaccinated girls also showed a reduction in HPV-related disorders; but this could have easily and perhaps more convincingly been attributed to the nationwide vitamin D supplementation programs, which were completely ignored and never mentioned despite the fact that vitamin D has been proven effective against HPV infections via a variety of levels of evidence.

Their concluding statement ‘The bivalent vaccine is confirmed as being highly effective vaccine and should greatly reduce the incidence of cervical cancer’ is overzealous and is an epidemiologic error when they failed to consider any other interpretive options. Indeed, such considerations – controlling for other possible factors – is the defining characteristic of competent epidemiology.

The authors followed their egregious overstatement (quoted previously) with a confirmatory understatement: ‘It is possible therefore that vaccine effectiveness was over-estimated.’ Neither the accompanying editorial nor the publications for the mass media mention of the probable overestimation of vaccine effectiveness.

My rapid response to the original article is as follows:

“Scotland’s public health campaigns to improve vitamin D nutriture occurred within the same timeframe as HVP vaccination

In April 2019, Palmer et al published a retrospective population study crediting vaccination against human papilloma virus (HPV) with reduction in HPV prevalence in Scotland, and the authors attributed a reduction in HPV prevalence among unvaccinated women with ‘herd protection.’

However, the authors did not mention Scotland’s population-wide public health campaigns to address endemic vitamin D deficiency. The Scottish Government recognized the high prevalence of vitamin D deficiency in its population and began recommending vitamin D supplementation not later than 2006. Vitamin D deficiency results in impaired mucosal and immune defenses and correlates in a dose-dependent manner with increased cervicovaginal HPV infection. By 2009, coincident with the start of the HPV vaccination campaign in 2008, numerous vitamin D supplementation (and sun exposure) campaigns were being implemented throughout Scotland to combat the documented population-wide problem of vitamin D deficiency.

Our views of vitamin D experienced a paradigm shift in the early part of this century with landmark publications such as Vieth’s authoritative documentation of safety in 1999, Zittermann’s ‘Vitamin D in preventive medicine’ in British Journal of Nutrition in 2003, and Vasquez’s ‘Clinical importance of vitamin D (cholecalciferol): a paradigm shift with implications for all healthcare providers’ in 2004 followed by an important partial summary of vitamin D usage guidelines in British Medical Journal in 2005.

These and similarly themed articles have contributed to increased awareness of vitamin D’s safety and roles in preventive medicine and public health, including reducing the burden of 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, use of vitamin D supplementation began to increase slowly and then exponentially in the United States and other countries, especially English-speaking societies, most notably the United Kingdom.

Indeed, according to the Scottish Health Survey 2003, use of dietary supplements such as vitamins (including vitamin D), fish oils (a source of vitamin D) and minerals (magnesium supplementation improves vitamin D status and is necessary for vitamin D activation, binding, transport, metabolism, and gene expression) had already begun to increase between 1998 and 2003. Certainly not later than 2006, the Scottish Government was already recommending widespread use of vitamin D supplements to combat the high prevalence of vitamin D deficiency in Scotland.

Widespread vitamin D deficiency in Scotland was followed by widespread recommendations for vitamin D supplementation starting in 2006 and 2009. In 2006, Burleigh and Potter published in Scottish Medical Journal stating that, ‘The prevalence of vitamin D deficiency is high in older outpatients in this geographical area.’ In 2007, Hyppönen and Power 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 further specified that ‘Vitamin D deficiencyis widespread in Scotland.’ In 2009, the Scottish Government acknowledged the need to educate its population about the importance of vitamin D3 supplementation. From that time until the present, the Scottish Government, United Kingdom National Health Services, and various advocacy groups and programs (e.g. ScotsNeedVitaminD.com, Healthy Start, which provides vitamin D supplements to all children and pregnant women in Scotland) continue assertive public health campaigns recommending vitamin D supplementation and increased vitamin D production via sun exposure via the ‘Shine on Scotland’ program initiated in 2009 for all of its citizens.

Vitamin D supplementation has been the subject of many clinical trials documenting anti-inflammatory, antiviral, and anticancer benefits. Correction of vitamin D deficiency has significant anti-inflammatory and immunomodulatory benefits. Vitamin D and its direct metabolites promote production of antimicrobial peptides which have antibacterial and antiviral properties, while also reducing viral replication by inhibiting the NF-kappaB pathway.

Vitamin D administration displays impressive clinical effectiveness against dermal HPV as shown in case reports, clinical series, and placebo-controlled trials, with remarkable safety, high efficacy, and a consistent trend toward complete resolution of lesions. In 2014, Schulte-Uebbing et al published ‘Chronical cervical infections and dysplasia (cervical intraepithelial neoplasia [CIN] 1-2): vaginal vitamin D treatment’ showing that among 200 women with cervical dysplasia, vitamin D vaginal suppositories (12,500 IU, 3 nights per week, for 6 weeks) provided ‘very good anti-inflammatory effects’ and ‘good antidysplastic effects’ in women with CIN 1.

In 2017, Vahedpoor and colleagues published a double-blind placebo-controlled trial of vitamin D in women with HPV, in which they found that vitamin D3 administration for 6 months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism and antioxidant status.
In 2018, Vahedpoor and colleagues published a double-blind placebo-controlled trial of vitamin D in women with HPV, in which they observed, ‘The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively’, thereby clearly favoring treatment with vitamin D over placebo.

In Scotland, programs advocating HPV vaccination (started in 2008) and vitamin D supplementation (started not later than 2006 and again in 2009) occurred in close chronologic proximity. Crediting the reduction in HPV-related disease solely to vaccination via retrospective population study is potentially invalid and misleading, especially when the authors make no account whatsoever of the national program for vitamin D supplementation which started in the same timeframe.

Numerous studies have shown that vitamin D provides immunomodulatory, anti-inflammatory, microbiome-modifying, antiviral and anti-HPV benefits with high safety, good efficacy, low cost, wide availability, and clinically important collateral benefits.”

Read the third part of the article

yogaesoteric
October 26, 2019