Vitamin D is one of the most utilised ingredients in supplement formulas, with clinical research suggesting its benefits in immunomodulation, calcium absorption and reducing inflammation. Knowing that the vitamin could positively alter the immune system through various mechanisms, the Medical University of Graz proposed that it might also influence cellular pathways of MS disease pathology.
To test this theory, the institute investigated the effects of vitamin D supplementation on a rat model that mimicked the cortical pathology of progressive MS (PMS).
To find out more, Annabel Kartal-Allen spoke to Michaela Tanja Haindl from the Department of Neurology, Medical University of Graz.
The study
During the trial, male rats aged 10–12 weeks were used to determine the impact of vitamin D on disease progression, oxidative stress levels and cortical demyelination — all hallmarks present in PMS — during a 45 day period.1
The animal model was specifically developed to accurately depict the cortical pathology observed in patients with the disease, as other rat models don’t exhibit this trait.
By utilising this model, the disease characteristics of human PMS are more accurately replicated, which enhances the translatability of the findings to the human situation, allowing more accurate and informed conclusions to be drawn from the study. 
The results
PLP loss reduction: In the group of rats supplemented with vitamin D (VD+), researchers at the Medical University of Graz found that the loss of proteolipid protein (PLP) — commonly associated with maintaining the structural integrity of myelin — was significantly reduced compared with the un supplemented (VD–) group.
Maintaining PLP levels that are closer to those seen in healthy individuals has the potential to lead to a reduced breakdown of the myelin sheath, which could notably impact the symptoms of patients with PMS. This is because of the significance that demyelination has in the disease’s pathology.2
Owing to this phenomenon, it’s feasible that vitamin D could work to alleviate the impacts of PMS by modulating myelin-influencing mechanisms.
VD+ animals exhibited a reduction in the activation of microglial cells
Reduction in microglial activation: As well as diminishing PLP loss, the VD+ animals exhibited a reduction in the activation of microglial cells. These specialised cells are heavily involved in propagating immune responses to protect the nervous system; but, they’re often associated with the instigation of symptoms in MS patients owing to their heightened and disproportionate immune response to self-antigen cells in traditional disease phenotypes.3
Vitamin D may reduce the impact of these aberrant microglial forms by suppressing their activation or facilitating the neuroprotective phenotype and reducing the disease burden in patients.
Presence of apoptotic cells: Cells undergoing apoptosis are another relevant piece of the puzzle when discussing the pathology of MS; they result from the inflammatory attacks on nerve cells that are characteristic of the disease’s progression in various models.4
The study results indicated that the VD+ rats experienced a significant reduction in the prevalence of apoptotic cells compared with the VD– group, suggesting that with regular supplementation, vitamin D may also potentially reduce the number of apoptotic cells in humans with PMS by positively influencing the mechanisms leading to apoptosis.
Neuronal preservation: The final positive influence that vitamin D had in the study was its ability to preserve neuronal structures.
Though this phenomenon was observed in study participants, the reasoning behind it is currently unknown, though researchers at the Medical University of Graz propose the role of astrocytes. Further research is currently exploring the mechanisms behind the neuronal preservation seen in this study.
How vitamin D may benefit MS patients
The positive impacts that vitamin D elicits on MS progression in this study most likely result from a multitude of factors, Michaela explains: “Vitamin D’s role in modulating the immune system, as well as human neurobiology, is multifaceted; our study supports this sentiment. The vitamin appears to be able to support neuroprotective mechanisms and may inhibit pathways that can exacerbate disease progression.”
“The wide range of mechanisms by which vitamin D can influence immunity and neuronal functionality give it the potential to be a valuable agent in reducing disease activity and progression. However, the efficacy and optimal dosage in a therapeutic context is currently subject of controversial discussion, so further research is required to fully elucidate its benefits and possible side-effects.” 
Michaela Tanja Haindl from the Department of Neurology, Medical University of Graz
Starting supplementation early
With positive results seen in the later disease stages of MS, it raises the question: could this effect ward off progression better if supplementation begins early? Michaela believes that this would be a sensible approach: “It’s highly advisable to monitor the vitamin D levels present in the body and supplement as necessary, especially for the early stages of MS. If given at an appropriate dosage, it could help to manage debilitating symptoms and improve general quality of life.”
“I would recommend this practice to anyone, whether they are ill or healthy. However, it’s important to be aware that vitamin D is a fat-soluble vitamin, which means that it’s possible to overdose. Therefore, no one should supplement with high doses without knowing their own serum levels.”
“It’s also important to note that the mechanisms of action of vitamin D can vary among healthy and ill individuals, age groups and genders, so a one-size-fits-all measurement of optimal vitamin D dosage isn’t realistic.”
Difficulties when studying vitamin D
Although the study by the Medical University of Graz points towards vitamin D supplementation being beneficial for patients with PMS, the lack of standardisation throughout the study groups could be painting an unrealistic picture:
“The challenges associated with researching the effects of vitamin D in clinical studies are manifold and contribute to often contradictory results. Owing to the lack of standardisation in measurement methods, different laboratories will employ various analytical parameters, leading to a high variability in results. Experimental models, on the other hand, offer the desired standardisation, but results cannot be directly extrapolated to humans.”
There are no unified standards for normal vitamin D levels in the population, which can complicate the interpretation of research findings
Another challenge is the intricacy of the vitamin itself: “Vitamin D and its metabolites further complicate the research process. It has several structurally similar forms that may differ in biological activity, which can often alter measurement outcomes and skew interpretation of the results."
"Furthermore, there are no unified standards for normal vitamin D levels in the population, which can complicate the interpretation of research findings. Studies will use different definitions for adequate, insufficient or deficient vitamin D levels, which makes things difficult when trying to compare studies.”
The combination of these factors leads to well-designed studies producing seemingly contradictory results, underscoring the need to enhance and standardise research methods to achieve more reliable and consistent outcomes.
Determining vitamin D’s full impact
There are multiple indications that vitamin D could be beneficial when treating PMS, although there is still a long way to go before this claim can be substantiated. Michaela stresses: “The findings from various studies present a complex picture. Some suggest that high levels of vitamin D might have protective effects against MS progression and could potentially reduce the relapse rate, but we need to do more to confirm the accuracy of these statements.”
“Determining the true impact of the vitamin on well-being and disease progression in patients with PMS could prove highly beneficial for a group that traditionally has few treatment options and poor outcomes. Therefore, we believe it’s important that the industry bands together to standardise study protocols and figure out the true story.”
References
1 www.mdpi.com/2072-6643/15/15/3309.
2 https://pubmed.ncbi.nlm.nih.gov/32973782/.
3 www.ncbi.nlm.nih.gov/pmc/articles/PMC5499932/.
4 www.ncbi.nlm.nih.gov/pmc/articles/PMC9316123/.
