It is a pain if public funded studies do not publish their results.
New work by Harvard colleagues shows how sunshine hormone D constrains inflammation by modulating the expression of key genes on chr17q. It builds on earlier collaborative work on the vitamin D receptor in 2004 (see their ref 5) as well on my annotation of IKZF3 (aka aiolos aka god of winds) in 2008 and again in 2022.
While our focus on allergy development was on vitamin D supplementation of newborns, the interest of Weiss et al. was on vitamin D deficiency in pregnancy. Vitamin D deficiency may not be attributed to the rise of the asthma and allergy epidemic although this remains the never ending obsession of Weiss et al.
Nevertheless, also a wrong hypothesis may lead to new insights. IKZF3 clearly is a key player where more recently heterozygous missense/LOF variants have been found in families with B-lymphopenia and EBV-associated lymphoma while the allergy proning effect is more in the 5-prime region.
The new study shows (again) that cholecalciferol suppresses the activation of the IL-2 pathway. But what is the net effect of artifical cholecalciferol exposure on naive T cells? Unfortunately the new paper narrowly focuses on cytokine production in Th2 cells only and even misses the famous Cantorna review that clearly says
Since 1983 it has been described that 1,25(OH)2D inhibited T cell proliferation and the secretion of select cytokines after mitogen stimulation. Moreover, 1,25(OH)2D directly inhibited IL-2 and IFN-γ transcription [17,18]. More recently 1,25(OH)2D has also been shown to inhibit IL-17 secretion by Th17 cells. The effects of 1,25(OH)2D on Th2 cells is more controversial with evidence that 1,25(OH)2D inhibits IL-4 transcriptionally as well as evidence that 1,25(OH)2D upregulates IL-4 in mouse and human T cells.
So we need to rephrase the finding of an “immune protective effect of vitamin D in allergic lung inflammation” to an overall “immune suppressive effect of vitamin D” which is basic textbook knowledge. Unfortunately the early origin of allergy induction remains a mystery.
It is again an U, no doubt.
we have now at least 36 studies…
Cheung and colleagues reports a survey conducted in 15 countries exploring the health and nutrition claims made in the marketing of infant formula products. The authors performed a systematic search of websites, examined packaging of formula products, and documented claims made about the formula product and citations of scientific evidence supporting those claims…
Health professionals and families lack the time to properly scrutinise claims. Industry is unlikely to change its practice given shareholder interests. Self-regulation has not worked, and responsible, ethical marketing by the formula industry seems unlikely.
There is an interesting retraction notice
The article “Vitamin D supplementation during pregnancy inhibits the activation of fetal membrane NF-κB pathway, by N. Gurkan, published in Eur Rev Med Pharmacol Sci 2022; 26 (16): 5926-5931-10.26355/eurrev_202208_29532-PMID: 36066168” has been retracted by the author as she stated that Vitamin D was used in the study as supplement and not a drug without the permission of the Ministry. Although Vitamin D is a commonly used supplement during pregnancy, the Local Ethics Committee accepted it as a drug and asked for it to be approved by the Ministry of Health. Therefore, the manuscript has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/29532
In contrast to most other endocrinologists I think that the decision is correct. Vitamin D is been chemically synthesized prohormone, underlies quality control, has benefits and side effects, could be even toxic, so it should be treated as a drug. Cudos to the Local Ethics Committee.
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
rs10174949 2:8302018 LINC00299
rs10178845 2:8303773 LINC00299
rs5743566 4:38804221 TLR1
rs2101521 4:38809830 TLR1
rs5743565 4:38804262 TLR1
rs45588337 4:38805607 TLR1
rs55830619 4:38805643 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.
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.
Das mit dem Halbwissen mag stimmen. Stand der Wissenschaft ist nicht die dubiose Modellrechnung eines Epidemiologen, sondern die Metaanalysen bzw Clinical Trials von Manson 2029, Neale 2022, O’Connor 2022 die zu der neuesten JAMA Empfehlung gestern geführt haben.
Pooled analyses also showed that vitamin D supplementation was not associated with any difference in cancer mortality (pooled OR, 0.94 [95% CI, 0.86-1.03]; 9 RCTs; n = 100 465) or cancer incidence (OR for any cancer, 0.98 [95% CI, 0.92-1.03]; 19 RCTs; n = 86 899) compared with placebo. However, the 2 largest trials of vitamin D supplementation (VITAL, n = 25 871 and D-Health, 21 310) that reported on cancer mortality had point estimates for effect size that were on opposite sides of null (ORs, 0.82 and 1.15).
Also wieder Mal ein Beispiel von “false balance”, denn Vitamin D in Nahrungsmitteln (warum auch noch in Nahrungsmitteln?) kann keine krebsbedingte Todesfälle verhindern.
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.
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.
or the 2020 Singh paper
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?
On Aug 12, Science magazine published a strange journalistic article of an ongoing vitamin D asthma study. I responded on the next day
— Matthias Wjst (@science_surf) August 13, 2021
while now also the former editor-in-chief of Science Jeremy Berg noted
This is some of the most irresponsible and intellectually lazy science journalism I have seen from a venue like @sciencemagazine that should, indeed must, do better
— Jeremy Berg (@jeremymberg) October 27, 2021
Science printed the rebuttal of Berg
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…
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.
Unfortunately the response of the news editor Tim Appenzeller is so weak that I would recommend to search now not only for a new correspondent but also a new editor.
Es gibt diverse Pro Vitamin D Webseiten, die den Gebrauch von Vitamin D als Rattengift (Rodentizid) bestreiten etwa das “Institut VitaminDelta, Dr. med. Raimund von Helden, Timmerschlade 14, 57368 Lennestadt” Zitat
… wurde ab 1984 wieder aufgegeben, weil die Ratten meist keinen Schaden nahmen.
Das ist Unsinn, Cholecalciferol wird sogar vermehrt wegen Resistenzen gegen Antikoagulantien eingesetzt. Fraßköder sind ab 2mg/kg wegen der Hypercalcämie auch für Haustiere wie Hund oder Katze tödlich.
Eine Pressemitteilung des Bundesverbandes aller Verbraucherzentralen weist auf ein Urteil des Landgerichts München I hin:
Erfolg gegen irreführende Werbung bei Nahrung für Kleinkinder: Das Landgericht München I hat einer Klage des Verbraucherzentrale Bundesverbands (vzbv) gegen die Hipp GmbH & Co. Vertrieb KG Recht gegeben. Demnach sind mehrdeutige Werbeaussagen zum angeblichen Vitamin D- und Calciumbedarf von Kindern bei Milchersatzprodukten untersagt. „Verbraucherinnen und Verbraucher müssen bei Lebensmitteln für Kleinkinder darauf vertrauen können, dass die Unternehmen besonders verantwortungsbewusst handeln. Dazu gehören klare und deutliche Informationen über Vitamine und Nährstoffe“, sagt Susanne Einsiedler, Rechtsreferentin beim vzbv. „Eltern sollten nicht den Eindruck bekommen, dass bestimmte Produkte nötig sind, damit ihr Kind ausreichend versorgt wird. Kinder über einem Jahr brauchen in der Regel keine speziellen Lebensmittel“.
Auch wenn das Urteil noch nicht rechtskräftig ist, gehe ich noch einen Schritt weiter, es braucht überhaupt keinen Vitamin D Zusatz in der Säuglingsmilch, auch nicht in der Anfangsmilch, es wird längst zuviel direkt supplementiert.
Der Vitamin D Hype schadet mehr, als dass er nützt. Orales Vitamin D kann zu späteren Allergien führen, auch wenn Fachgesellschaften die Vitamin D Supplementierung aus Tradition weiterhin unkritisch sehen.
Es ist ja ein lustiger Experte, dieser Dr. med Jürgen Hower, den HiPP da auf der Webseite in einem “Interview” präsentiert neben der hauseigenen Wissenschaftlerin. Seine wissenschaftliche Leistung in der Endokrinologie besteht darin, bei Kindern in seiner Gemeinschaftspraxis Vitamin D Spiegel bestimmt zu haben. Ansonsten vermarktet er mit Vitamin D gepanschte Schokolade als “Dr. Chococo”.
Nichts Neues also unter der Sonne – ich erinnere mich an Aktenberge im Bundesarchiv Berlin, in denen sich einschlägige Geschäftemacher schon vor 80 Jahren einen jahrelangen Streit mit den Behörden lieferten.