NICE, Vitamin D & Covid-19

Executive Summary

* The UK National Institute for Care & Health Excellence (NICE) undertook a rapid review of vitamin D for the treatment and prevention of Covid-19. The review was published in December 2020.

* Three research questions were asked about 1) vitamin D as a treatment for Covid-19, 2) vitamin D for prevention of Covid-19 and 3) any associations observed between vitamin D and Covid-19 outcomes.

* NICE found one randomised controlled trial (RCT) to consider for question 1, no RCTs for question 2 and 12 population/case control type studies for question 3.

* The one RCT examining vitamin D for treatment of Covid-19 found that administration of vitamin D at hospital admission significantly reduced the likelihood of being admitted to ICU and no one treated with vitamin D died. The odds ratios were striking.

* The 12 studies examining the association between vitamin D levels and incidence of Covid-19 and/or severity of Covid-19 (including survival from) were conducted in many different countries by many different research teams. Vitamin D levels were reviewed as absolute levels and as deficient or sufficient levels.

* Two UK studies (using Biobank data) found nothing statistically significant. The other 10 studies all concluded that higher/sufficient vitamin D levels were associated with significantly better outcomes from Covid-19. The risk ratios for lower/insufficient vitamin D levels were striking in many cases – up to 15-fold difference in one study and often beyond the 2-fold difference used as a starting point for causality with the Bradford Hill criteria.

* Every single study, every single piece of evidence, was dismissed in the NICE document as “very low” in quality and at “serious risk of bias” or “very serious risk of bias.”

* I saw a lot of evidence to support vitamin D being a valuable intervention to lessen the likelihood of bad outcomes (including death) from Covid-19. NICE essentially concluded “move along – there’s nothing to see here.”

Introduction

The UK National Institute for Care & Health Excellence (NICE) undertook a rapid review of vitamin D for the treatment and prevention of Covid-19. The review was published in December 2020 (Ref 1). The committee undertaking the work asked three research questions:

Research questions

1) What is the clinical effectiveness and safety of vitamin D supplementation for the treatment of Covid-19 in adults, young people, and children?

2) What is the clinical effectiveness and safety of vitamin D supplementation for the prevention of SARS CoV2 infection (and subsequent Covid-19) in adults, young people, and children?

3) Is vitamin D status independently associated with susceptibility to developing Covid-19, severity of Covid-19, and poorer outcomes from Covid-19 in adults, young people, and children?

The three key words in these research questions are 1) treatment 2) prevention and 3) association. The search for evidence was conducted on the period 2002 to October 27th, 2020. This allowed for other coronaviruses, such as SARS CoV1 (symptomatic) and MERS, to be included as indirect evidence. It transpired that only Covid-19 studies were included.

Outcomes of interest

The main outcomes of interest for research questions 1 and 2 were mortality (all-cause and Covid-19 related) and Intensive Care Unit (ICU) admissions. There were a number of secondary outcomes of interest including hospitalization, ventilation, time to clinical cure, complications, and others. I haven’t listed all the secondary outcomes of interest because, as you will see, only one study ended up being considered as evidence for Question 1 and no studies ended up being considered as evidence for question 2.

The outcomes of interest for research question 3 were:

– Incidence of Covid-19 (laboratory/virologically confirmed)

– Covid-19 rate (laboratory/virologically confirmed)

– Severity of confirmed Covid-19 (for example, but not limited to, Centers for Disease Control and Prevention definition, World Health Organization definition, proxy such as hospitalisation, ventilation, ICU admission, and others)

– Poor outcomes (for example, mortality, complications, morbidities post infection, long Covid).

Inclusion & exclusion criteria

The inclusion criteria for research questions 1 and 2 were: systematic review of randomised controlled trials (RCTs); RCTs; and controlled clinical trials. The exclusion criteria for research questions 1 and 2 were: case-control studies; cross section studies; case series and case reports; and qualitative studies (Ref 2).

The inclusion criteria for research question 3 were: systematic review of non-randomised studies; prospective and retrospective cohort studies; case-control studies; cross-sectional studies; and case series. The exclusion criteria for research question 3 were case reports.

Studies found meeting criteria

For research question 1, one study was included (Entrenas Castillio et al 2020 RCT Spain) (Ref 3).

For research question 2, no studies were included.

For research question 3, 12 studies were included (see below).

I checked the studies found with a vitamin D expert, who knows the literature far better than I do, and he thought that the committee had found the studies that met their criteria. I am proceeding on the basis that the studies available for each of these research questions are as presented in the report.

The results

Research question 1

The one study included to answer this research question was conducted in a hospital in Spain. This study involved 76 patients who were hospitalised with lab-confirmed Covid-19. They were randomised in a 2:1 ratio to the treatment arm or the control arm; so 50 people ended up in the treatment arm and 26 in the control arm. The treatment was administration of oral calcifediol (vitamin D3) (0.532 mg) on the day of admission. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on days 3 and 7, and then weekly until discharge or ICU admission. People in the control arm were not given any vitamin D. Other treatment between the patients remained the same.

Of the 50 patients treated with calcifediol, 1 required admission to ICU (2%) while, of 26 untreated patients, 13 required admission (50%). That was a statistically significant and clinically significant difference. Of the patients treated with calcifediol, none died, and all were discharged without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, 2 died and the remaining 11 were discharged.

The odds ratio (OR) for ending up in ICU was 0.02 (95 %CI 0.002−0.17) for the treatment group vs the no-treatment group. That was almost a 0% chance of the vitamin D group ending up in ICU. When the results were adjusted for differences between the two groups for hypertension and type 2 diabetes, the odds ratio was still 0.03 (95 %CI: 0.003-0.25).

The NICE document dismissed this evidence as “very low” in quality and at “very serious risk of bias” for ICU admission and as “very low” in quality and at “very serious risk of bias” for mortality.

Research question 2

NICE found nothing to examine for the research question about prevention.

Research question 3

NICE found 12 studies to help with the research question – is there any evidence for vitamin D being associated with developing Covid-19 or the severity of Covid-19 if diagnosed? The 12 studies were all from 2020. Two studies each came from France, the UK, the US, and from Spain and one each came from China, Germany, Israel, and Turkey. The studies were mainly of population studies and case-control studies.

We’ll whizz through them – extracting the salient point from the original papers. (I’m going to keep numbers and confidence intervals to a minimum for ease of reading. All of these can be found in the paper abstracts, which the references can point you to. Many of the findings are so significant in the normal sense of the word, that confirmation of the statistical significance will just clutter the narrative).

1) Annweiler et al. Retrospective quasi-experimental study France (Ref 4).

The first Annweiler et al study involved 66 frail elderly residents in a French nursing home with an average age of 88. The intervention group was defined as all residents diagnosed with Covid-19 who received an oral dose of 80,000 IU vitamin D3 either in the week following the suspicion or diagnosis of Covid-19, or during the previous month. This definition placed 57 people in the intervention group and 9 in the control. 82.5% of participants in the Intervention group survived Covid-19, compared to 44.4% in the Comparator group.

The researchers concluded that vitamin D supplementation was independently associated with less severe Covid-19 and better survival rate.

The NICE document dismissed this evidence as “very low” in quality and at “very serious risk of bias.”

2) Annweiler et al. Retrospective cohort study France (Ref 5).

The second Annweiler et al study involved 77 patients hospitalised for Covid-19 in a geriatric unit with an average age of 88. Group 1 (29 people) regularly supplemented with vitamin D over the previous year. Group 2 (16 people) were supplemented with vitamin D after Covid-19 diagnosis and the comparator group (Group 3 – 32 people) received no vitamin D supplementation. In Group 1, 93% of Covid-19 participants survived at day 14, compared to 81% survivors in Group 2 and 69% survivors in Group 3.

The researchers concluded that vitamin D supplementation was independently associated with less severe Covid-19 and better survival rate.

The NICE document dismissed this evidence as “very low” in quality and at “very serious risk of bias.”

3) Hastie et al. Retrospective cohort study UK (Ref 6).

The Hastie et al study examined the UK Biobank data between 16th March and 14th April 2020 for lab confirmed Covid-19 and patient vitamin D levels. Complete data were available for 348,598 participants. Of these, 449 had confirmed Covid-19. After adjustments, vitamin D was not associated with infection rates. The most interesting finding is surely how low the incidence of Covid-19 was given that the peak of the UK Covid-19 curve was 8th April, 2020.

The researchers’ findings did not support a potential link between vitamin D concentrations and risk of Covid-19 infection.

The NICE document dismissed this evidence as “very low” in quality and at “very serious risk of bias.”

4) Hernández et al. Case-control study Spain (Ref 7).

The Hernández et al study examined 216 Covid-19 patients and 197 population-based controls (average age 60-61) to see if vitamin D levels were associated with the incidence of Covid-19. Vitamin D deficiency was found in 82% of Covid-19 cases and 47% of population-based controls (Ref 8).

The researchers concluded that vitamin D levels were lower in hospitalised Covid-19 patients than in population-based controls and that these patients had a higher prevalence of deficiency.

The NICE document dismissed this evidence as “very low” in quality and at “serious risk of bias.”

5) Karahan and Katkat. Case-control study Turkey (Ref 9).

The Karahan and Katkat study examined 149 patients (average age 64) hospitalised with Covid-19 for severity and/or mortality. 47 patients had moderate Covid-19; 102 patients were severe-critical. Average blood vitamin D levels were significantly lower in patients with severe-critical Covid-19, compared with moderate Covid-19 (Ref 10). Vitamin D insufficiency was present in 93% of the patients with severe-critical Covid-19.

The researchers concluded that vitamin D was independently associated with mortality in Covid-19 patients.

The NICE document dismissed this evidence as “very low” in quality and at “serious risk of bias.”

6) Kaufman et al. Retrospective cohort study US (Ref 11).

The Kaufman et al study examined over 190,000 patients (average age 54) from the 50 US states and matched them with vitamin D level results (25(OH)D) from the preceding 12 months. The SARS-CoV-2 positivity rate was higher (at 12.5%) in the 39,190 patients with “deficient” vitamin D (<20 ng/mL) than in the 27,870 patients with “adequate” vitamin D (30–34 ng/mL) (8.1%) and the 12,321 patients with values ≥55 ng/mL (5.9%). The association between 25(OH)D levels and SARS-CoV-2 positivity produced an R2 value of 0.96, which indicated strong correlation in the total population (strong is an understatement with an R2 of 0.96).

The researchers concluded that SARS-CoV-2 positivity was strongly and inversely associated with circulating vitamin D levels, a relationship that persisted across latitudes, races/ethnicities, both sexes, and age ranges.

The NICE document dismissed this evidence as “very low” in quality and at “very serious risk of bias.”

7) Macaya et al. Case series Spain (Ref 12).

The Macaya et al study examined 80 patients with lab confirmed Covid-19 seen at the emergency department of a hospital where recent vitamin D (25(OH)D) levels were known. Vitamin D deficiency was associated with an increased risk of developing severe Covid-19 (after adjusting for all relevant factors.) The odds ratio was 3.2 – which is beyond a level at which causation can start to be assessed.

The researchers concluded that vitamin D deficiency did show an association with severe Covid-19 infection.

The NICE document dismissed this evidence as “very low” in quality and at “very serious risk of bias.”

8) Meltzer et al. Retrospective cohort study US (Ref 13).

The Meltzer et al study examined 489 patients (average age 49) at an urban medical centre for whom vitamin D levels had been measured within the previous year. Between March 3rd, and April 10th, 2020, 71 of these patients tested positive for Covid-19. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. Testing positive for Covid-19 was associated with vitamin D deficiency (relative risk 1.77) when compared with vitamin D sufficiency. Predicted Covid-19 rates in the deficient group were 21.6% vs 12.2% in the sufficient group.

The researchers concluded that vitamin D deficiency was associated with increased Covid-19 risk.

The NICE document dismissed this evidence as “very low” in quality and at “serious risk of bias.”

9) Merzon et al. Case-control study Israel (Ref 14).

The Merzon et al Israeli study examined 14,000 members of a health service who were tested for Covid-19 between Feb 1st, and April 30th, 2020, who had at least one previous blood test for their 25(OH)D level. Suboptimal vitamin D levels in this study were defined as < 30 ng/mL. The 782 people who tested positive for Covid-19 had significantly lower average vitamin D levels. People with low vitamin D levels had an increased likelihood of Covid-19 infection (1.58 times) and increased likelihood of hospitalization (2.09 times).

The researchers concluded that “low plasma 25(OH)D levels appear to be an independent risk factor for COVID-19 infection and hospitalization.”

The NICE document dismissed this evidence as “very low” in quality and at “serious risk of bias.”

10) Radujkovic et al. Retrospective cohort study Germany (Ref 15).

The Radujkovic et al study examined 185 patients diagnosed with Covid-19 who presented at a German health centre. Vitamin D status was assessed at the time of admission. Vitamin D (25(OH)D) deficiency was set at a low bar of < 12 ng/mL. During an average period of 66 days, 93 patients required hospitalisation; 28 patients had a severe outcome (IMV/D – invasive mechanical ventilation and/or death). Among these 28 severe outcomes, there were 16 deaths. A total of 41 patients were vitamin D deficient. When adjusted for age, gender, and comorbidities, vitamin D deficiency was associated with higher risk of IMV/D and death. The risk ratios were 6.12 for IMV/D and 14.73 for death.

The researchers concluded that “our study demonstrates an association between vitamin D deficiency and severity/mortality of COVID-19.”

The NICE document dismissed this evidence as “very low” in quality and at “serious risk of bias.”

11) Raisi-Estabragh et al. Nested case-control study UK (Ref 16).

The Raisi-Estabragh et al studywas the second study to use the UK Biobank data. This study specifically examined men and Black, Asian, and Minority Ethnic (BAME) individuals, as these were patients identified as at higher risk of a poor outcome from Covid-19 than women and non-BAME individuals. This study asked a different research question and I’m not sure that it should have been included. It sought to see if any factors (of which vitamin D was just one) could explain why men and BAME individuals were having worse outcomes.

A total of 4,510 people were assessed. The study confirmed "there was over-representation of men and BAME ethnicities in the COVID-19 positive group." However, the study couldn’t explain why. The conclusion was: “In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors.”

This mattered little anyway as the NICE document dismissed this evidence as “very low” in quality and at “very serious risk of bias.”

12) Ye et al. Case-control study China (Ref 17).

The Ye et al study compared the vitamin D (25(OH)D) levels and rates of vitamin D deficiency between 80 healthy controls and 62 patients diagnosed with Covid-18 and admitted to a hospital in China. Cases were categorized into asymptomatic, mild/moderate, and severe/critical disease. The vitamin D concentration in Covid-19 patients was much lower than that in healthy controls. Vitamin D levels were the lowest in severe/critical cases, compared with mild cases. Significantly higher rates of vitamin D deficiency were found in Covid-19 cases (42%) compared to healthy controls (11%). Vitamin D deficiency was the greatest in severe/critical cases (80%), compared with mild cases (36%).

The researchers concluded that vitamin D was associated with Covid-19 severity and added "a potential threshold of 25(OH)D (41.19nmol/L) to protect against COVID-19 was identified.”

The NICE document dismissed this evidence as “very low” in quality and at “very serious risk of bias.”

Summary

The one RCT examining vitamin D for treatment of Covid-19 found that administration of oral calcifediol (vitamin D) at hospital admission significantly reduced the likelihood of being admitted to ICU and no one treated with vitamin D died. The odds ratios were striking.

There were 12 studies (largely population and case control studies) examining the association between vitamin D levels and incidence of Covid-19 and/or severity of Covid-19 (including survival from). The studies were conducted in many different countries by many different research teams. Vitamin D levels were reviewed as absolute levels and as deficient or sufficient levels. The two UK studies using Biobank found nothing statistically significant. The other 10 studies all concluded that higher/sufficient vitamin D levels were associated with significantly better outcomes from Covid-19. The risk ratios for lower/insufficient vitamin D levels were striking in many cases – up to 15-fold difference in one study and often beyond the 2-fold difference used as a starting point for causality with the Bradford Hill criteria (Ref 18).

Every single study, every single piece of evidence, was dismissed in the NICE document as “very low” in quality and at “serious risk of bias” or “very serious risk of bias.”

Look at the evidence for yourself and decide if NICE were right to dismiss it all as they did. Look at the evidence for yourself and ask – can I (or my loved ones) really risk having low or insufficient vitamin D levels right now? Ask yourself – is there anything to lose by taking a vitamin D supplement for the foreseeable future and for my loved ones to do the same? (Ref 19). You may also like to ponder, as I found myself doing, why NICE would dismiss such a cheap, safe, and effective nutrient, which seems highly likely to help and does no harm.

 

References

Ref 1: https://www.nice.org.uk/guidance/ng187/evidence/evidence-reviews-for-the-use-of-vitamin-d-supplementation-as-prevention-and-treatment-of-covid19-pdf-8957587789
Ref 2: https://www.zoeharcombe.com/2020/08/the-hierarchy-of-evidence/
Ref 3: Entrenas Castillo et al. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study.; J Steroid Biochem Mol Biol. 2020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456194/
Ref 4: Annweiler et al. Vitamin D and survival in COVID-19 patients: A quasi-experimental study. 2020. The Journal of steroid biochemistry and molecular biology.
https://pubmed.ncbi.nlm.nih.gov/33065275/
Ref 5: Annweiler et al. Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study. Nutrients. 2020.
https://pubmed.ncbi.nlm.nih.gov/33147894/
Ref 6: Hastie et al. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes & metabolic syndrome. 2020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204679/
Ref 7: Hernandez et al. Vitamin D Status in Hospitalized Patients With SARS-CoV-2 Infection. The Journal of Clinical Endocrinology & Metabolism. 2020.
https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgaa733/5934827
Ref 8: In COVID-19 patients, mean ± standard deviation 25OHD levels were 13.8 ± 7.2 ng/mL, compared with 20.9 ± 7.4 ng/mL in controls (P < .0001).
Ref 9: Karahan, S. and Katkat, F. Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey. Journal of Nutrition, Health and Aging. 2020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533663/
Ref 10: The differences were quite striking 10.1 ± 6.2 vs. 26.3 ± 8.4 ng/mL, respectively, p<0.001.
Ref 11: Kaufman et al. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PloS one. 2020.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239252
Ref 12: Macaya et al. Interaction between age and vitamin D deficiency in severe COVID-19 infection. Nutricion hospitalaria. 2020.
https://pubmed.ncbi.nlm.nih.gov/32960622/
Ref 13: Meltzer et al. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA network open. 2020.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770157
Ref 14: Merzon et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. The FEBS journal. 2020.
https://pubmed.ncbi.nlm.nih.gov/32700398/
Ref 15: Radujkovic et al. Vitamin D Deficiency and Outcome of COVID-19 Patients. Nutrients. 2020.
https://pubmed.ncbi.nlm.nih.gov/32927735/
Ref 16: Raisi-Estabragh et al. Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank. Journal of public health (Oxford, England). 2020.
https://academic.oup.com/jpubhealth/article/42/3/451/5859581
Ref 17: Ye et al. Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity? A Case-Control Study. Journal of the American College of Nutrition. 2020.
https://www.tandfonline.com/doi/full/10.1080/07315724.2020.1826005
Ref 18: https://www.zoeharcombe.com/2016/09/the-bradford-hill-criteria/
Ref 19: Eating a 200g tin of oily fish with the bones and skin will provide approximately 15mcg of vitamin D, which is a basic intake. Who consumes this daily? Sunbathing is a natural way to acquire vitamin D, but not possible for most people for many months of the year.

30 thoughts on “NICE, Vitamin D & Covid-19

  • avatar
    April 13, 2021 at 8:10 pm
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    Of course while there is a lot of talk about vitamin D and Covid the thing that is being missed or forgotten is that good levels of D will help with how your body copes with flu and other virus’s that will no doubt be back when Covid dies down.

    Colin

    Reply
  • avatar
    March 25, 2021 at 1:32 pm
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    Somebody must be paying some attention to Vitamin D as a friend of mine who is recovering from breast cancer and still on prescription drugs found that her GP had added vitamin D to her prescription! Didn’t say why or even inform her!

    Reply
    • avatar
      March 25, 2021 at 3:28 pm
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      Hi Casie
      That’s a nice story! Thanks for sharing that :-)
      Best wishes – Zoe

      Reply
  • avatar
    March 8, 2021 at 1:30 pm
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    Pre-print of article (not peer reviewed) analyzing the Castillo Spanish small trial. It goes into the possible reasons NICE found the trial unconvincing, concluding through mathematical analysis that the strength of the trial results overcome the perceived weaknesses in randomization.

    https://www.medrxiv.org/content/10.1101/2020.11.08.20222638v2

    Abstract
    A randomized controlled trial of calcifediol (25-hydroxyvitamin D3) as a treatment for hospitalized COVID-19 patients in Córdoba, Spain, found that the treatment was associated with reduced ICU admissions with very large effect size and high statistical significance, but the study has had limited impact because it had only 76 patients and imperfect blinding, and did not measure vitamin D levels pre- and post-treatment or adjust for several comorbidities. Here we reanalyze the reported results of the study using rigorous and well established statistical techniques, and find that the randomization, large effect size, and high statistical significance address many of these concerns. We show that random assignment of patients to treatment and control groups is highly unlikely to distribute comorbidities or other prognostic indicators sufficiently unevenly to account for the large effect size. We also show that imperfect blinding would need to have had an implausibly large effect to account for the reported results. Finally, comparison with two additional randomized clinical trials of vitamin D supplementation for COVID-19 in India and Brazil indicates that early intervention and rapid absorption may be crucial for the observed benefits of vitamin D. We conclude that the Córdoba study provides sufficient evidence to warrant immediate, well-designed pivotal clinical trials of early calcifediol administration in a broader cohort of inpatients and outpatients with COVID-19.

    Reply
    • avatar
      March 8, 2021 at 11:36 pm
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      Well, here is an interesting follow up. A scathing take-down of the Jungreis and Kellis article.

      http://compbio.mit.edu/calcifediol/PachterBlogPostCopy_Calcifediol_2020-11-17.pdf

      Here is a taste:

      Unfortunately, the “mathematical analysis” of Jungreis and Kellis is deeply flawed, and their “theorem” is vacuous.
      Their analysis cannot be used to conclude that the Córdoba study shows that calcifediol significantly reduces ICU
      admission of hospitalized COVID- 19 patients. Moreover, the Córdoba study is fundamentally flawed, and therefore
      there is nothing to learn from it.

      Reply
      • avatar
        March 9, 2021 at 10:09 am
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        Hi Steven
        Many thanks for these finds – much appreciated
        Best wishes – Zoe

        Reply
  • avatar
    February 27, 2021 at 7:03 pm
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    I wonder what the NICE judgement would be on the evidence supporting the USDA food guidelines. It is too bad that there will never be such a review. If the same “preponderance of the evidence” standard employed by the USDA were applied to vitamin D, vaccines would not even have been pursued. And the ramifications for population health might be similar in severity.

    Reply
  • avatar
    February 26, 2021 at 7:23 pm
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    If the NICE reject the role of Vit D in the prevention/symptom reduction of COVID 19, why is our local prison giving it to prisoners for free ?
    Ok, the dose is low (one 1000iu tablet a day), but surely a waste of public money if NICE think there is “nothing to report”.

    Reply
    • avatar
      February 26, 2021 at 8:28 pm
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      Hi Andrew
      Many thanks for your comment – I didn’t know that.
      1000iu is pretty good = 25mcg – which is ahead of the current SACN 15mcg recommendation. This used to be only 10mg until a couple of years ago.
      Lucky prisoners!
      Best wishes – Zoe

      Reply
  • avatar
    February 24, 2021 at 9:58 am
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    I have written to the Welsh Government about this many times …. no response. The real question is one of dosage. Is 4000iu/day safe ? The answer is yes and within UK regulatory guidelines. In this terrible pandemic would the average person wish to take 400iu/day [NICE guidelines] or 4000iu/day ? I cannot speak for the average person but then neither should the Government. Give them the information and let them decide for themselves.

    Dr Peter Hilton …. retired ITU Consultant.

    Reply
    • avatar
      February 24, 2021 at 2:55 pm
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      Hi Peter
      Many thanks for your comment. I saw some correspondence with the Welsh government which was basically “we’ll do whatever NICE says”

      What was the point of devolution then?!

      I’m totally with you – share the evidence and let people decide. Instead of why take vitamin D, my view now is – why not?!

      I’ve been on 2,000iu all winter daily – same for mum. Hubby is on 4,000iu. Brother is on 10,000iu – his choice…

      Best wishes – Zoe

      Reply
  • avatar
    February 24, 2021 at 9:41 am
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    Been testing and supplementing last 4 years and N=1 results suggest massive reduction respiratory virus symptoms despite very regular exposures.
    It was the one thing that could have been implemented rapidly when CoV2 arrived. Just imagine the number of lives that could have been saved by effective Vit D doses. Disappointing that the government dismissed it but sadly our health care system fails to understand its true significance.
    Benefits go beyond Covid19 too, eg vascular health, autoimmune disease and some cancers.

    Reply
    • avatar
      February 24, 2021 at 2:51 pm
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      Hi Jenny
      Good points – thank you. Vitamin D has many functions.
      Best wishes – Zoe

      Reply
  • avatar
    February 24, 2021 at 9:32 am
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    Thank you Zoe. Plain common sense. In the northern hemisphere most people are vitamin D deficient during the winter months hence why there is so much more illness. I’ve been upping my levels for years after I had a very bad respiratory condition one winter. I now recommended it to anyone I meet or know. I’m surprised NICE have taken their stance against Vitamin D as it is a cheap alternative but may be they too are on the vaccine payroll.

    Reply
  • avatar
    February 23, 2021 at 4:12 pm
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    I would urge people to look at the actual NICE paper, which I did. I haven’t read it in any detail, which would be hard in the time I had available, but I did look at the bits relevant to the Spanish study, and if there is any explanation of how this paper was at high risk of bias, I didn’t see it. Yes, they concluded that there was a high risk of bias, but they didn’t say why. had they said – there was a high risk of bias, for the following reasons, a, b, c, etc, I would accept that. As it is, I am left wondering if NICE have a bias themselves.

    Reply
  • avatar
    February 23, 2021 at 2:41 pm
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    Slowly but surely, seems to me that ” too much too late” is not working. However, if your d level is routinely OK, your chance to get infection is smaller. It would count. It should count. Do measure d level while healthy; at hospital door is too late…actually instead of measuring, take some for security.
    JR

    Reply
  • avatar
    February 23, 2021 at 9:17 am
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    I seem to remember Malcolm Kendrick writing about the use of Vit D about a year ago and recommending it. He probably wasn’t alone. There has been plenty of time for NICE to organise a proper RTC. I wonder why they haven’t – ££££££££££££££££ ?

    Reply
    • avatar
      May 30, 2021 at 11:07 am
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      There is only one reason: if there is an available first-line treatment they would not have gotten the emergency approval for the vaccinations.

      Reply
  • avatar
    February 22, 2021 at 11:02 pm
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    Dear Zoe.

    Are you aware that the authors of the study acknowledge that it was not an RCT?
    https://pubpeer.com/publications/DAF3DFA9C4DE6D1B7047E91B1766F0#11

    “In summary, it is not a RCT as we explain in methods, although patients were randomly assigned to treated or non-treated group.”
    “All comments about RCT are not applicable here since the study does not have a placebo group that it is clearly specified in limitations. It is an observational study as is clearly specified in introduction and methods.”

    So, if this was not an RCT and you mention that “The inclusion criteria for research questions 1 and 2 were: systematic review of randomised controlled trials (RCTs); RCTs; and controlled clinical trials” does this count as a controlled clinical trial, so as to be included in answering question 1?

    It also seems that the pre print has been removed:
    https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3771318
    “Dear Preprints with the Lancet Readers,

    We have removed this preprint due to concerns about the description of the research in this paper. This has led us to initiate an investigation into this study.”

    By the way I don’t disagree with the statement that Vitamin D is “cheap, safe, and effective nutrient, which seems highly likely to help and does no harm.”

    I just want to make sure that the one principal study that you cite in your note has a high level of scrutiny as you are well known to do on so many other studies.

    Reply
  • avatar
    February 22, 2021 at 9:55 pm
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    Very good analysis. I fear that many people simply read that NICE has found against using vitamin D and assume that they are right without reading the report(s). They are after all the “authority”, no matter how implausible the assessment. The proper response of NICE if they were really unconvinced would have been to recommend the commissioning of a carefully designed rigorous RCT. Instead the two applications for government funding were turned down.

    Reply
    • avatar
      February 24, 2021 at 5:21 pm
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      I think they decided to down play the possible benefits in case people started to neck down 4000iu per day then meet 50 friends for a rave. See the quote in “…” in the excerpt from the Guardian article.

      Reply
    • avatar
      February 24, 2021 at 5:39 pm
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      Hello David Davis, MP? If it is you, thank you for taking up the case for vitamin D in parliament, and would writing to my MP to ask for a fuller explanation from NICE be helpful?

      It seems to me that the only rationale for the NICE conclusions is to manipulate the behaviour of people so that they stick to lockdown rules and do not engage in activities likely to spread the virus because they have taken vitamin D. Sometime in the future it is likely that vitamin D will be adopted internationally as a preventative measure against COVID-19, and then the government will be held responsible for lives lost because they did not seize the opportunity to implement a programme of supplementation.

      I think NICE report is deliberately and cynically lying to the public on this issue because somebody has decided that the public is not to be trusted with this information.

      Reply
  • avatar
    February 22, 2021 at 9:36 pm
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    Thanks Zoe for a wonderful Blog, as usual.
    How can NICE keep claiming that “there is not enough evidence to support using vitamin D in the Covid-19 pandemic”? If you do not look, you do not see. Zoe certainly looks, and she certainly sees. Zoe, you put NICE to shame.
    See also my Blog from today : “NICE demands more human sacrifice”:
    http://www.drdavidgrimes.com/2021/02/covid-19-vitamin-d-after-barcelona-more.html

    Reply
  • avatar
    February 22, 2021 at 7:11 pm
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    NICE needs to be held responsible for the consequences.

    Reply
  • avatar
    February 22, 2021 at 12:39 pm
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    Unbelievable. Is it possible for you to send your article to NICE, or to your MP? There are questions to be answered about bias, not to mention a huge waste of public money if there is no actual discussion of the results.

    I am wondering what they meant by ‘risk of bias’? Everyone would like to find something to mitigate the effects of the virus, surely that isn’t bias? Or maybe NICE is biased against vitamin D in case people decide to not have the vaccine but just take a supplement instead. Thanks to you, we are aware that there is a specialist in human behaviour on SAGE.

    Reply
    • avatar
      February 22, 2021 at 12:54 pm
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      Okay, so here is a paragraph from an article from 10 January 21 which explains NICE’s stance, I think:

      ‘For UK public health experts, perhaps wary of overstated claims of vitamin D’s benefits, the case for downplaying the link to coronavirus initially mostly depended on retrospective studies and there was no official call for more research. One such recent paper considered by Nice, using vitamin D levels measured up to 14 years ago, found no link between vitamin D levels and more severe illness or mortality from Covid-19, but in another paper the lead author called for high-quality trials to ascertain whether vitamin D plays a beneficial role in the prevention of severe coronavirus reactions. “For now, recommendations for vitamin D supplementation to lessen Covid-19 risks appear premature and, although they may cause little harm, they could provide false reassurance leading to changes in behaviour that increase risk of infections,” they (NICE people?) concluded. This baffles Davis and Huq. And they believe that now is the chance to begin to erode the UK’s deficiency.’

      Davis is David Davis and Hui is Rupa Huq, both MPs. I’m so glad there are independent thinkers in parliament.

      Reply
      • avatar
        February 22, 2021 at 12:54 pm
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        And the article is in The Guardian

        Reply
        • avatar
          February 22, 2021 at 2:44 pm
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          So what is your explanation of why NICE would overlook Vit D evidence?

          Presumably due to the criteria for assessing the quality of evidence? And lack of balance with an evaluation of (limited) potential harms. NICE have to be seen to use a standardised approach to evaluating evidence. And there’s no “big vitamin” industry lobbying those on the committee to recommend vit D?

          Reply
  • avatar
    February 22, 2021 at 12:22 pm
    Permalink

    Thank you for this superb review

    Study No 6 is an excellent example of how an observational study can give us useful information

    See my comment below about “Observation of 190,000 people” and take time to read the original paper

    Then ask yourself – why did NICE reject this paper ?

    In addition I think that NICE missed 2 significant studies that did not match their strict search criteria for Randomised Control Trials

    1. Bradford Hill Criteria

    2. Causal Inference

    Observation of 190,000 people
    ========================
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239252

    190,000 people in USA matched 3 criteria:
    1. They had a test for COVID-19 between March-June 2020
    2. They had a blood test for Vitamin D in the 12 months previous
    3. Their ZIP code was available

    Results:
    1. If their blood level for Vitamin D was > 30 ng/ml they had half the COVID-19 positivity than people whose blood level was < 20 ng/ml
    2. People with darker skin had lower blood levels, so likely to have worse outcomes

    Note:
    UK definition of deficiency is < 10 ng/ml, so the effect would be greater in UK

    More here:
    http://vitaminduk.com/vitamin-d-big-news-about-coronavirus/

    Benefit: R-number reduced by half ?

    Bradford Hill Criteria
    ================
    http://www.drdavidgrimes.com/2020/11/covid-19-vitamin-d-demonstration-of.html

    Please see the commentary by Dr David Grimes that Bradford Hill’s Criteria had been met
    http://vitaminduk.com/vitamin-d-big-news-about-coronavirus/

    Causal Inference
    =============
    https://www.medrxiv.org/content/10.1101/2020.05.01.20087965v2

    I think that this is stronger than an RCT ( & worthy of a Nobel prize for medicine ! )
    1.4 million observations from 239 locations in the northern hemisphere:
    http://vitaminduk.com/vitamin-d-big-news-about-coronavirus/

    All this information is from my Zoom conference of September 24th
    http://vitaminduk.com/vitamin-d-big-news-about-coronavirus/

    A report about this was sent to NICE on September 27th
    http://vitaminduk.com/vitamin-d-correspondence-with-nice-phe-sacn/

    Were NICE and their experts correct, or were they “influenced” to publish this Guidance, or were they incompetent ?
    .

    Reply

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