Vitamin D intake and multiple sclerosis risk in the Norwegian Mother, Father and Child cohort, 2025, Kapali et al.

[SNT Gatchaman]

Vitamin D intake and multiple sclerosis risk in the Norwegian Mother, Father and Child cohort

Spoiler: Authors

Akash Kapali; Anne Kjersti Daltveit; Kjell-Morten Myhr; Kjetil Bjornevik; Karine Eid; Marte-Helene Bjørk; Anne Lise Brantsæter; Trond Riise; Marianna Cortese

BACKGROUND
Higher vitamin D has consistently been associated with a lower multiple sclerosis (MS) risk, but some controversy remains about whether this is due to vitamin D itself or sunlight.

METHODS
We conducted a prospective study among women participating in the Norwegian Mother, Father and Child Cohort Study, recruited in 2002–2008 and followed until 2022. We identified incident MS cases through data linkage with the Norwegian MS Registry. Total vitamin D intake from food and supplements was obtained from validated food frequency questionnaires completed in pregnancy. We estimated HRs for MS and 95% confidence intervals (CI) using Cox regression.

RESULTS
Among 78 074 participants, 349 developed MS during follow-up. Their median daily vitamin D intake was 296 international units (IU) compared with 333 IU among women who did not develop MS. Higher total vitamin D intake was associated with a 42% lower MS risk (HR comparing top vs bottom quintile 0.58, 95% CI 0.38 to 0.89, ptrend<0.01). The results were similar when adjusting for age at delivery, total energy intake, pre-pregnancy body mass index and smoking. The associations were similar for vitamin D intake from food (HR for top vs bottom quintile 0.70, 95% CI 0.47 to 0.1.04, ptrend=0.02) and supplements (HR for ≥600 IU/day vs <200 IU/day 0.65, 95% CI 0.41 to 1.04, ptrend=0.01).

CONCLUSIONS
In this prospective study, higher vitamin D intake was associated with lower MS risk in women living in Norway, where there is insufficient sun-induced vitamin D production during most of the year. This supports the hypothesis that vitamin D itself modifies MS risk.

Web | DOI | PDF | Journal of Neurology, Neurosurgery & Psychiatry | Paywall

 

[Midnattsol]

The difference in median intake is not particularly high. For reference the typical supplemental dose sold in Norway is 400IU/10mcg.

The associations were similar for vitamin D intake from food (HR for top vs bottom quintile 0.70, 95% CI 0.47 to 0.1.04, ptrend=0.02) and supplements (HR for ≥600 IU/day vs <200 IU/day 0.65, 95% CI 0.41 to 1.04, ptrend=0.01)

This throws me. The highest intake from food would likely not be close to intake og someone who supplements, so if you find an association between the highest and lowest quintiles for food but not supplements then a) the dose needed for the effect is lower than the lowest supplement or b) other nutrients in the food that also contains vitamin D might be responsible for the effect. Vitamin D is found mainly in seafood which include other relevant nutrients such as selenium and omega 3s.

 

[Utsikt]

Did they correct for date of birth to account for sum exposure during pregnancy?

What about place of birth? Northern Norway gets substantially less sun than the south.

 

[Mij]

The D-lay MS trial had their participants take 100,000ius every 2 weeks for 24 months.

Conclusions and Relevance Oral cholecalciferol 100 000 IU every 2 weeks significantly reduced disease activity in CIS and early relapsing-remitting MS. These results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy.

 

[Dolphin]

The difference in median intake is not particularly high. For reference the typical supplemental dose sold in Norway is 400IU/10mcg.


This throws me. The highest intake from food would likely not be close to intake og someone who supplements, so if you find an association between the highest and lowest quintiles for food but not supplements then a) the dose needed for the effect is lower than the lowest supplement or b) other nutrients in the food that also contains vitamin D might be responsible for the effect. Vitamin D is found mainly in seafood which include other relevant nutrients such as selenium and omega 3s.

Not sure why you are saying this when the associations for food and supplements were very similar?

The associations were similar for vitamin D intake from food (HR for top vs bottom quintile 0.70, 95% CI 0.47 to 0.1.04, ptrend=0.02) and supplements (HR for ≥600 IU/day vs <200 IU/day 0.65, 95% CI 0.41 to 1.04, ptrend=0.01)

 

[Utsikt]

Not sure why you are saying this when the associations for food and supplements were very similar?

The associations were similar for vitamin D intake from food (HR for top vs bottom quintile 0.70, 95% CI 0.47 to 0.1.04, ptrend=0.02) and supplements (HR for ≥600 IU/day vs <200 IU/day 0.65, 95% CI 0.41 to 1.04, ptrend=0.01)

Wouldn’t you expect a stronger association with the higher dose (i.e. supplements)?

 

[Utsikt]

The D-lay MS trial had their participants take 100,000ius every 2 weeks for 24 months.

Conclusions and Relevance Oral cholecalciferol 100 000 IU every 2 weeks significantly reduced disease activity in CIS and early relapsing-remitting MS. These results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy.

Made a thread:

https://www.s4me.info/threads/high-dose-vitamin-d-in-clinically-isolated-syndrome-typical-of-multiple-sclerosis-2025-thouvenot-et-al.47427/

 

[Dolphin]

Wouldn’t you expect a stronger association with the higher dose (i.e. supplements)?

Perhaps (though the post I replied to didn’t seem to say that) though perhaps only a fraction of it is properly absorbed and active if co-factors from appropriate food aren’t ingested at the same time? Lots of supplement studies in general (not specifically on vit D) seem to have poor results.

 

[Mij]

We need sufficient levels of magnesium for converting vit D into its active form. I had very low vit D levels over 25 years ago but taking supplements didn't help much until I took magnesium shots and my D levels went up by taking 1000iu to 2000iu/daily.

 

[Midnattsol]

Not sure why you are saying this when the associations for food and supplements were very similar?

The associations were similar for vitamin D intake from food (HR for top vs bottom quintile 0.70, 95% CI 0.47 to 0.1.04, ptrend=0.02) and supplements (HR for ≥600 IU/day vs <200 IU/day 0.65, 95% CI 0.41 to 1.04, ptrend=0.01)

What I find odd is that the groups are so similar and I see no reason to separate them if it is only vitamin D intake, and not the behavior of taking supplements, that is studied.

Wouldn’t you expect a stronger association with the higher dose (i.e. supplements)?

The intakes here are low and I would not expect huge differences in blood concentrations to be honest. Norway is restrictive on vitamin D, it's only been a few years since it was allowed to sell supplements with 20mcg/800IU in pharmacies for example.

The recommended intake in Norway for the general population is 10mcg/400IU, and that is to achieve a blood concentration of ~50nmol/L (Norwegian reference range, Canada for example has >75 or 80 nmol/L, which has been recommended by the endocrine society for over 10 years). The differences in the reference ranges between countries is part of problem with vitamin D studies, as comparisons between a vitamin D sufficient group vs the insufficient control is often based on national reference guidelines. So one study that finds a difference could have a vitamin D sufficient group that has a vitamin D concentration of >75 nmol/L, while another looks at 50 nmol/l and finds not difference. This study does not add anything to alleviate those issues.

The results were similar when adjusting for age at delivery, total energy intake, pre-pregnancy body mass index and smoking

These adjustment does not take into account that intake of the food that contain vitamin D, and the behavior of taking supplements, is very different across different parts of the population and we are selecting for women of high socioeconomic status beyond just smoking/non smoking. Though for pregnant women in Norway, there has been numerous arguments for not eating fatty fish when pregnant due to environmental toxins so it's a toss if high socioeconomic status and presumed higher health literacy would mean lower vitamin D intake from seafood (but then this group would likely get more sunlight. It's a complicated field )

They also adjusted for total energy intake and when this is done someone who eats 5mcg vitamin D would be seen as similar to someone who eats 20 mcg vitamin D as long as the vitamin D intake relative to energy consumption is the same. These two individuals would have different vitamin D blood concentrations which is what is important for the biological effect (wholly made up numbers just to show how this works!). I do believe vitamin D can be helpful for the immune system (I also believe the same for near infrared light), but doing analysis like this is not making the matter clearer.

 

[forestglip]

I see no reason to separate them if it is only vitamin D intake, and not the behavior of taking supplements, that is studied.

I think it's meant to double check that it's really vitamin D. They saw the association when combined, but weren't really sure if it might be only due to nutritional vitamin D or only due to supplemental D. If the association holds no matter what the source, that adds some confidence that it's not a confounder like people who take supplements in general have less MS.

They also adjusted for total energy intake and when this is done someone who eats 5mcg vitamin D would be seen as similar to someone who eats 20 mcg vitamin D as long as the vitamin D intake relative to energy consumption is the same.

I think you might be thinking of normalizing based on total energy intake. Where 5 mcg in someone with a 1000 calorie diet might be considered equal to 10 mcg in someone with a 2000 calorie diet.

But when controlling for energy, they're seeing what effect a change in D causes if the energy intake is held constant. Basically, in people with identical calorie diets, does 10 mcg of D lead to less MS than 5 mcg?