Yep there was some hype about 100 years ago, soon after the discovery of vitamin D by Windaus – where vitamin D / cod liver oil was used to treat tuberculosis.
Also vitamin A (also contained in high doses in cod liver oil) was used in the pre-antibiotic era as anti-infective therapy while it has lost its role being used only as some supportive add-on after during measles infection. Reliable prevention of measles by vaccination should not be confused with uncertain supportive therapy.
But what about vitamin D supplementation and cancer? A new study in the Annals last week show
7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years (1817 vs. 1943 deaths; hazard ratio [HR], 0.93 [95% CI, 0.87 to 0.99]), along with a 6% increase in CVD mortality (2621 vs. 2420 deaths; HR, 1.06 [CI, 1.01 to 1.12]).
As both risks are of borderline significance and we don’t trust P values alone, my conclusion is: vitamin D supplementation doesn’t prevent cancer.
In addition to some programming questions, I have prompted several LLMs for a summary of my longstanding research question “vitamin D supplementation in the newborn period and later allergy”. Here is the elicit response:
Research on vitamin D supplementation in infancy and its relationship to later allergy development has yielded mixed results. Some studies suggest that higher vitamin D intake during the first year of life may increase the risk of atopic conditions later in childhood (Bäck et al., 2009; Hyppönen et al., 2004). These findings are supported by animal studies and epidemiological surveys linking early vitamin D supplementation to allergy development (Wjst, 2006). However, a randomized controlled trial found that high-dose vitamin D supplementation did not prevent allergic sensitization or diseases in infants compared to standard dosage, except for an increased risk of milk allergy in the high-dose group (Rosendahl et al., 2019). Interestingly, this study also observed that infants with high cord blood vitamin D levels had a higher risk of food allergen sensitization. These conflicting results highlight the complex relationship between vitamin D and allergy development, suggesting that both insufficient and excessive vitamin D levels may potentially influence allergic outcomes.
The limitation introduced by “however” is wrong – the whole story is not really conflicting if you read my earlier paper on a paradoxical reaction. I have been a reviewer of the Rosendahl paper and asked them to change their misleading spin. It is basically a triple blind study (the authors believed the opposite fact eg that vitamin D supplementation prevents while it induces allergy). Unfortunately, as Rosendahl et al. did not respond to my complaint, we can now clearly see how the bias of the authors is being injected into the LLM.
I dont know why there is still the discussion of any genuine understanding of LLMs as there is none, see Binz et al.
even though LLMs often achieve state-of-the-art performance on existing benchmarks, it remains debated whether this reflects genuine understanding, or whether they are merely acting like stochastic parrots […] When deciding whether to use an LLM, it is important to recognize that LLMs are simply models of word form distributions extracted from text—not models of the information that people might get from reading that text
Anyway, the workflow suggested by inkenai – putting these PDFs now into NotebookML for further analysis – is excellent.
A new paper from Bristol discusses the recent explosion of low-quality two-sample Mendelian randomization studies and offers a cure.
We advise editors to simply reject papers that only report 2SMR findings, with no additional supporting evidence. For reviewers receiving such papers, we provide a template for rejection.
We know it for ages (1985) that 1,25-Dihydroxyvitamin D3 suppresses human T helper cells by blocking interleukin 2 (IL 2) production. The immune effects were our main argument 2001 against oral vitamin D supplementation of newborns as it may induce later allergy . It is now funny to find now a clinical trial that tests low-dose interleukin-2 in birch pollen allergy.
to ask also chatGPT consensus some of my lifelong research questions
nothing wrong here but clearly not weighted at all. Maybe the consensus app need to learn also rules of meta-analysis and evidence based research in particular when attention to the details is decisive for epidemiology, immunology and clinical studies.
Ich hatte direkt nach der Wende in Halle und Leipzig die erste Ost-West Allergiestudie* durchgeführt und dabei die verblüffende Entdeckung gemacht, dass es im Osten nicht mal halb so häufig Allergien gab.
Der Grund dafür war uns zunächst nicht klar, aber dann stelle sich doch bald heraus, daß es wohl die unterschiedliche Vitamin D Prophylaxe war – im Westen gab es tägliche niedrige Dosen ab der ersten Lebenswoche, im Osten wurde ab dem 2. Monat wenig hohe hohe Einzeldosen verabreicht. Wenn Kinder im Osten krank waren, dann fiel auch immer wieder die eine oder andere Dosis aus, auch wurde das Schema nach meiner Recherche nicht immer komplett durchgezogen. Leider haben wir uns damals aber nur die Impfpässe angesehen, nicht aber die im Nachinein wichtigeren Wiegekarten.
DDR Wiegekarte. Quelle https://www.ddr-museum.de/de/objects/1011262Westdeutsches Untersuchungsheft U2. Quelle https://www.g-ba.de/downloads/83-691-452/2017-05-11_GBA_Kinderuntersuchungsheft_Web-WZ.pdf
Die Befürchtung der Professoren Mai und Beuren in dem alten SPIEGEL Artikel über Vitamin D Nebenwirkungen haben sich zum Glück nicht bewahrheitet. Dafür aber stellte sich dann aber eine unerwünschte immunologische Wirkung heraus die damals noch nicht bekannt war.
Mit dem aus England bzw Amerika importierten Schema zur Supplementierung stiegen die Allergien an. In der BRD war das ab den frühen 60er Jahren , wie überhaupt die englischsprachigen Länder immer die höchsten Allergiehäufigkeiten hatten, da sie wegen der häufigen Rachitis auch viel konsequenter supplementierten (die Rachitis hiess früher einmal auch “englische Krankheit”).
Der Mechanismus der Allergieentstehung ist dabei nur teilweise aufgeklärt: Vitamin D ist jedenfalls immunsuppressiv mit vielfacher Auswirkung auf B und T Zellen was seit dem Nachweis des Vitamin D Rezeptors auf diesen Immunzellen wissen. Die Supplementierung stört offensichtlich die initiale Klassifikation ob ein Protein harmlos oder allergen ist.
Warum es aber auch schon 1989 Allergien im Osten gab? Nun, es war ja keine Vitamin D freie Zone, offensichtlich sensibilisiert man sich auch noch ausserhalb des überkritischen Intervals in den ersten Lebenswochen.
It seems that I missed an interesting 2017 paper that looked for disease-associated SNPs in canonical DR3 motifs. Only 7 out of 211 traits showed significant hits, one of these was self-reported allergy. When annotating these SNPs, there are only two genes: LINC00299 and TLR1
So are TLR1 & LINC00299 variant carriers more susceptible to vitamin D induced allergy?
LINC00299 (Long Intergenic Non-Protein Coding RNA 299) is a RNA Gene of largely unknown function, associated so far with allergy only on a genetic level in Framingham, href=”https://pubmed.ncbi.nlm.nih.gov/23817569/”>23andme and other studies. We don’t know so much here, the function of the long non coding RNAs
depends on subcellular localization. Depending on their niche, they specifically interact with DNA, RNA, and proteins and modify chromatin function, regulate transcription at various stages, forms nuclear condensation bodies and nucleolar organization. lncRNAs may also change the stability and translation of cytoplasmic mRNAs and hamper signaling pathways. Thus, lncRNAs affect the physio-pathological states and lead to the development of various disorders, immune responses, and cancer.
The TLR1 genetic association is found by many genetic studies, while the clinical association is probably more by an infectious origin. TLR1 is a pattern recognition receptor with a specificity for gram-positive bacteria and also included in my forthcoming exome paper as a protective factor for asthma/allergy. And we are also close to my earlier review of vitamin D, the microbiome and allergy…
Does any co-infection response during first vitamin D exposure influence allergic sensitisation? There are indeed some hints of an short-lived effect of lung group 2 innate lymphoid cells (ILC2s)
Laboratory mice cohoused for 2 weeks had impaired ILC2 responses and reduced lung eosinophilia to intranasal allergens, whereas these responses were restored in mice cohoused for ≥2 months. … These findings suggest that ILC2s respond dynamically to environmental cues and that microbial exposures do not control long-term desensitization of innate type 2 responses to allergens.
I have criticized in the past the milk industry sponsored research that is now operating at a similar scale like research funded by cigarette industry [1]. And well, it seems that I am not alone here when reading a new CEA paper “Are paediatric allergy services promoting or harming public health?”
There were increasing and excessive sales of specialized formula designed for infants with milk allergy—either extensively hydrolysed or amino acid formula. These represented 7.6% of formula sold in 2019 … Although pediatric allergy services cannot be held solely to blame for whole population trends, there is evidence that the clinical guidance used in pediatric allergy clinics might promote or exacerbate these trends. Moreover, many allergy, gastroenterology and pediatric societies and professionals routinely flaunt public health guidance from the World Health Organization by continuing to accept funding from formula companies, despite World Health Assembly resolutions that such conflictive relationships should be avoided.
Just tried citationgecko.com on a topic that I have been working on for 2 decades. It will find rather quickly the source paper, much faster than reading through all of it. Unfortunately reviews are rated to be more influential than original data as Citation Gecko picks articles with many references.
Here is the ultimate and comprehensive summary written by two of the best vitamin D experts – Martineau and Cantorna
… lack of a consistent protective signal from RCTs reporting so far is reflected by the absence of any recommendation relating to prophylactic or therapeutic use of vitamin D for COVID-19 in guidelines from national or international bodies … If vitamin D does have favourable immunomodulatory effects in COVID-19, then demonstrating a meaningful clinical benefit of supplementation over existing standards of care is likely to become increasingly challenging, as ever more effective pharmacological therapies and vaccines emerge.
This year vitamin D nonsense information of the year comes by a plant biologist at Rothamsted Research in Harpenden, UK who wants to block a tomatoe conversion pathway leading to an “accumulation of the vitamin D precursor” (which reminds me of the 1930 attempts of mushroom irradiation to generate high amounts of vitamin D2).
Martin and her colleagues plan to study this, and have been given permission to grow their gene-edited tomatoes in fields. The team also hopes to measure the impact of outdoor UV light exposure on conversion of provitamin D3 to vitamin D3 in the plants’ leaves and fruit …You can only edit what you understand,” he says. “And it’s only because we understand the biochemistry that we’re able to make those sorts of interventions.”
Vitamin D supplements are clearly over rated according to a recent BMJ paper. No doubts that it is a bad idea to supplement an uncontrolled amount of an pro-hormone by eating tomatoes.
Fortunately with 0.2 μg/g or 8 IU D3/g dried tomatoe we are below toxicity levels.
This is basically an update of my 2017 Allergy paper where I asked about sequelae of early vitamin D supplementation.
Two extensively examined hypotheses are the hygiene hypothesis (lack of protective bacterial exposure which leads to subsequent allergy) and the vitamin D hypothesis (early vitamin D supplementation sensitizes newborns against allergens) … The interesting question is: Are these concepts exclusive? … There is some preliminary evidence that – like many other environmental factors –vitamin D may modify the human microbiome.
Only yesterday a paper popped up during a presentation of Amelie Baud about the influence of social partners and the gut microbiome. This 2018 study tested gut microbial composition from 16S rRNA sequencing during the first year of life and subsequent risk of asthma in 690 participants
1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 year … the microbial composition was not affected by maternal asthma status suggests that only susceptible children, exposed to inappropriate microbial stimulation during the first year of life, may express their inherited asthma risk …. The five most discriminating indicator OTUs for each cluster were identified for PAM cluster 1 as Enterobacteriaceae, Staphylococcus, Streptococcus, Bifidobacterium and Enterococcus, and for PAM cluster 2 as Faecalibacterium, Bacteroides(x3), and Anaerostipes … the risk of developing persistent asthma was increased (adjusted hazard ratio (aHR) 2.87 (1.25−6.55), P = 0.013) if the microbiome remained in PAM cluster 1 at age 1.
IMHO this doesn’t look very much like direct microbiome effects but some colliding factor. The authors discuss cesarean section-birth and antibiotics as relevant factors while I wonder why the last author (who is a known pro vitamin D lobbyist ) doesn’t take into account vitamin D here?
there was a significant association between community composition and vitamin D supplementation at the genus level. The vitamin D group had a higher abundance of genus Lachnospira, and lower abundance of genus Blautia (linear discriminate analysis >3.0). Moreover, individuals with 25(OH)D >75 nmol/L had a higher abundance of genus Coprococcus and lower abundance of genus Ruminococcus compared to those with 25(OH)D <50 nmol/L.
Vitamin D supplementation significantly increased gut microbial diversity. Specifically, the Bacteroidetes to Firmicutes ratio increased, along with the abundance of the health-promoting probiotic taxa Akkermansia and Bifidobacterium. Significant variations in the two-dominant genera, Bacteroides and Prevotella, indicated a variation in enterotypes following supplementation.
So is the microbiome just an indicator of vitamin D exposure in genetic susceptible children?
Piller minimizes the rationale used to select the placebo-controlled trial design and suggests that there is agreement that such a design is unethical… The News story notes that the majority of children in the trial were Black and states that this constitutes overrepresentation… Rather than being criticized, this trial should be commended for inclusion of appropriate trial participants…. Piller writes that participants were at increased risk of fractures and that the nine bone fractures experienced by study participants were more than anticipated, without specifying the magnitude of any increased risk or the anticipated number of fractures. However, there is no consensus that any increased risk exists…
as well as the response of Dr. Celedon in the same issue
Piller misrepresents the Vitamin D Kids Asthma Study (“Vit-D-Kids” or “VDKA”) . He reports concerns about the study’s design, participant safety and selection, consent forms, and report trans-parency. These doubts are unfounded. VDKA ethically investigated a potentially important treatment for childhood asthma.
Please read also the new Medium article by Dr Berg and the medRxiv article by Dr Celedon.
For whatever reason the story surfaced again yesterday at Bluesky. For posteriority here is an unrolled thread with some interesting new details by Dr. Berg.
Unfortunately some Twitter links expired recently but the links to the printed Science paper are still correct.
This is one of the most unfair attacks of a dubious science journalist on a reputable scientist.
I know Dr Celedon for several decades and although I never agreed on his opinion on high vitamin D demand in newborns, this discussion was always fair and on a high academic level.
The motivation of Piller is unclear. Most likely and as we found with other stories he wants to establish himself as an investigative “Woodward-Bernstein style” reporter on the cost of his victims.
The so called “ethics” experts of Piller missed the biological facts of vitamin D metabolism.
