Category Archives: Vitamins

U shape is good and bad

I did not expect that serum vitamin D levels are associated with mortality at both ends of the distribution as now shown by Dorup et al.

Out of 247,574 a total of 16.645 subjects died in the ensuing 0 -7 years. … 25-hydroxyvitamin D level of 70 nmol/L was associated with the lowest cardiovascular disease mortality risk … At the higher extreme (125 nmol/L), the hazard ratio of cardiovascular disease mortality was 1.3 (95% CI 1.2-1.4), with similar risk among men and women.

Following our first paper on U shaped vitamin D effects there are now many more papers show that effect. Vitamin D is not just good or bad, it is both depending on timing, dose, application, whatever.

 

U

A jubilee – today we have 1000 papers on allergy and vitamin D

It is a long time period from our first paper in July 1999 in Allergy, but more than 15 years later there is now a huge list of papers.

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When looking for potential paradigm shift in research, however, vitamin D is still largely ignored.

    • Professional organizations that give legitimacy to the paradigm: NONE
    • Dynamic leaders who introduce and purport the paradigm: FEW
    • Journals and editors who write about the system of thought: FEW
    • Government agencies who give credence to the paradigm: NONE
    • Educators who propagate the paradigm’s ideas by teaching it to students: NONE
    • Conferences conducted that are devoted to discussing ideas central to the paradigm: YES
    • Media coverage: MINOR
    • Lay groups, or groups based around the concerns of lay persons, that embrace the beliefs central to the paradigm: FEW
    • Sources of funding to further research on the paradigm: NONE

 

A large inter-individual variation for the efficiency of vitamin D3 supplementation

I believe this already since my first step into the vitamin D field but only now a review shows that

The integration of all these genome-wide data facilitates the identification of the most important VDR binding sites and associated primary 1,25(OH)2D3 target genes. Expression changes of these key genes can serve as biomarkers for the actions of vitamin D3 and its metabolites in different tissues and cell types of human individuals. Analysis of primary tissues obtained from vitamin D3 intervention studies using such markers indicated a large inter-individual variation for the efficiency of vitamin D3 supplementation.

It is a continuous medical malpractice to supplement newborn children with vitamin D without taking into account variation of the inter-individual response, body weight, or any co-medication.

Cycling is good for you (and vitamin D is an activity marker)

Vitamin D level is an activity or lifestyle marker, although this has been largely neglected in the medical literature, maybe except Gannage 2000, Hyppönen 2007, Sohl 2013 and Choi 213. A new paper by de Rui in PLoS now shows that

serum 25OHD levels were significantly higher in individuals who engaged in outdoor pastimes … compared to those who did not. In particular, subjects regularly practicing gardening or cycling had higher serum 25OHD levels than those who did not, whereas 25OHD levels differed little between subjects who did or did not undertake indoor activities.

While these are good news for older cyclists Continue reading Cycling is good for you (and vitamin D is an activity marker)

Take care of your last sentence

I have been told long ago to take care of the last sentence in a paper, avoiding any unjustified conclusion or any unwarranted speculation. Let’s start with a fully justified last sentence in the new volume of  “International Nutrition: Achieving Millennium Goals and Beyond

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It says that Continue reading Take care of your last sentence

Vitamin D “priming”

We have recently put forward the hypothesis, that an early intra-uterine may be priming the vitamin D system – I will soon send also another abstract to the forthcoming Vitamin D Workshop.
Today I found a new paper that may also support this view although it examines vitamin D toxicity:

Recent cases of intoxication relate to errors in manufacturing, formulation or prescription, involve high total intake in the range of 240,000 to 4,500,000 IU and present with severe hypercalcemia, hypercalciuria or nephrocalcinosis. However, mild hypercalcemia and hypervitaminosis using currently recommended doses has been reported in infants with rickets.

My interpretation is that children adjusted to live with very low vitamin levels get even mild hypercalcemia with recommended vitamin D doses, yea, yea.

The best vitamin D paper in 2013

I have probably two candidates here. The first one is by the Cantorna group in October 2013 and provides for the first time a link between between the gut microbiome and oral vitamin D exposure. We all thought that vitamin D has no influence on bacteria as they cannot utilize it. But that doesn’t seem to be true as the composition of the microbiome may change.

Mice that cannot produce 1,25(OH)2D3 [Cyp27b1 (Cyp) knockout (KO)], VDR KO as well as their wild-type littermates were used. Cyp KO and VDR KO mice had more bacteria from the Bacteroidetes and Proteobacteria phyla and fewer bacteria from the Firmicutes and Deferribacteres phyla in the feces compared with wild-type. In particular, there were more beneficial bacteria, including the Lactobacillaceae and Lachnospiraceae families, in feces from Cyp KO and VDR KO mice than in feces from wild-type … Our data demonstrate that vitamin D regulates the gut microbiome and that 1,25(OH)2D3 or VDR deficiency results in dysbiosis, leading to greater susceptibility to injury in the gut.

So while I always thought, oral vitamin D supplementation may have a direct effect on the gut mucosal system, this paper opens a completely new avenue. Continue reading The best vitamin D paper in 2013

Reference values should be based on reference populations and not on politics

For a long time this has been a general rule. Just take the mean and substract two standard deviations and you get some useful reference values. Or whatever algorithm you like. This changed considerably where commercial or any other personal interests come into play. The cholesterin discussion settled only by studies showing that people with a history of cardiovascular disease may derive benefit from statins irrespective of their cholesterol levels.
I see some analogy in the vitamin D field. There is a German dermatologist who believes that 60% of all Germans are vitamin D deficient (the comments following the interview highlight this as an epiphany “totale Erleuchtung”). And a more recent paper showed that “89.9%” of all healthy newborns being insufficient. Really looks like a mix-up of some basic concepts in clinical medicine, yea, yea.

The first proven risk factor for allergy

After more than a century of research, the first successful clinical trial of an allergy risk factor has been performed. It looks like the authors even did not anticipate such an effect (known as triple blind design). But read what the Pubmed article about the Norizoe et al. paper says

To elucidate whether maternal vitamin D supplementation during lactation improves infantile eczema and other subsequent allergic disorders, a randomized, double-blind, placebo-controlled trial was performed.
Mothers (n=164) of infants with facial eczema at one-month checkup were randomly assigned to receive vitamin D3 supplements (n=82; 800 IU/day) or placebo (n=82) for 6 weeks from May 2009 to January 2011. The primary outcome was infantile eczema quantified by Scoring Atopic Dermatitis (SCORAD) index at the three-month checkup, and the secondary outcomes were atopic dermatitis, food allergy, and wheeze diagnosed by doctors up to 2 years of age.
There was no significant difference in SCORAD at 3-month checkup between two comparative groups. Doctor-diagnosed food allergy was significantly more common up to age 2 years in vitamin D group (10/39: 25.7%) than in placebo group (3/40: 7.5%; RR=3.42, 95%CI=1.02 to 11.77, P=0.030). Moreover, at least one secondary outcome was also significantly more common in vitamin D group (17/39: 43.6%) than in placebo group (7/40: 17.5%; RR=2.49, 95%CI=1.16 to 5.34, P=0.012).
These results suggest that vitamin D supplementation may not decrease the severity of infantile eczema at three months of age, but may rather increase the risk of later food allergy up to two years of age. Because a large number of subjects was lost to follow-up, further study is needed to confirm the findings.

Of course, there may be some weakness in the study design, a large loss to follow-up and the way how food allergy was diagnosed will be critized. I think, however, that this is a major breakthrough that raises the hope that we will finally understand how allergy develops.

Addendum Dec 23th, 2013

I should have added “true” risk factor, as there are positive trials on probiotics and atopic dermatitis. The meta-analysis by Lee immediately lead to a rebuttal

Their review fails to meet published standards for the quality of systematic reviews on several criteria, and this has led to inappropriate conclusions. […] These defects in methodologic rigor have led to an exaggeration of the clinical benefits of probiotics for eczema prevention.

The Cochrane Summaries are also negativ

There is not enough evidence to recommend using probiotics for the treatment of eczema.

Same situation with asthma

We found no evidence to support a protective association between perinatal use of probiotics and doctor diagnosed asthma or childhood wheeze

The best vitamin D paper in 2012

The turn of the year may not only indicate many new chances but also allow a higher standpoint. IMHO the best paper in the vitamin field was published by Rousseau Gama in the BMJ 2012;345 :e5706.

We measured serum C reactive protein and 25-hydroxyvitamin D concentrations before and two days after elective knee or hip surgery in 30 patients. After surgery the mean serum concentration of C reactive protein increased (5.0 (SD 5.5) v 116.0 (81.2) mg/L; P <0.0001), whereas serum 25-hydroxyvitamin D decreased (56.2 (30.3) v 46.0 (27.6) nmol/L; P <0.0006).

The reasons are not fully clear but the results are consistent with two other studies reporting a fall in serum 25-hydroxyvitamin D concentration during a systemic inflammatory response. So, it looks like 1 simple study will make 1000 other studies useless. That seems to be the beauty of science… although I do not understand how that related to a serum half-life of two weeks?
So far I argued that vitamin D is always a lifestyle proxy e.g. pubmed/22698792) but there maybe also biological reasons.
BTW I would also have a candidate for the worst vitamin D paper, just in case, ….

Prevision

In my recent review on vitamin D and allergy I introduced the rather new concept of epigenetic priming of the offspring’s vitamin D system. I could find only a limited number of studies supporting this view. Fortunately, there is a new study published today that gives me some support. Using a twin design the authors (AJCN. First published ahead of print May 30, 2012 as doi: 10.3945/ajcn.112.035683) find

Our results suggest that maternal circulating 25(OH)D is the most significant regulator of neonatal circulating 25(OH)D concentrations, with underlying genetic factors playing a limited role.

The 5 most important papers on vitamin D and respiratory infections in asthma

Ginde AA et al., Vitamin D, respiratory infections, and asthma, Current Allergy and Asthma Reports 2009:

Substantial evidence now indicates that vitamin D may enhance the innate immune response and protect against respiratory infection. The human cathelicidin hCAP- 18 appears to have a particularly important role in the vitamin D–mediated mechanism against infection. Additionally, early evidence suggests that vitamin D modulates regulatory T-cell activity and IL-10 production, which are critical to the Th1–Th2 balance. These findings may be particularly important in the pathogenesis, control, and severity of asthma. However, Continue reading The 5 most important papers on vitamin D and respiratory infections in asthma

Deadly vitamin D

A German newspaper ( Ärztezeitung ) reports that vitamin D deficiency apparently increases all-time death rate.

Ein Mangel an Vitamin D erhöht offenbar die Sterberate.
Eine Studie in den USA hat ergeben, dass 70 Prozent der knapp 11.000 untersuchten Erwachsenen einen Vitamin-D-Mangel hatten.
Das Sterberisiko war in dieser Gruppe dreimal so hoch wie bei Personen ohne einen Mangel an dem Sonnenvitamin.

Looking at the original paper it appears Continue reading Deadly vitamin D

Handout text 2011 AAAAI Seminar San Francisco Vitamin D deficiency

2011 AAAAI Annual Meeting Handout

Session Number: 3523
Session Title: Vitamin D: Vitamin D Deficiency Causes Asthma -> CON
Session Start: 3/20/2011 12:45 AM
Matthias Wjst, Munich

Welcome to the third major symposium on vitamin D and asthma at the AAAAI. Continue reading Handout text 2011 AAAAI Seminar San Francisco Vitamin D deficiency

Will they ever read the literature?

Although the authors of this new JACI paper claim to having done a systematic review they even missed two key papers that even contradict the statement above Continue reading Will they ever read the literature?