Magnetic resonance imaging (MRI) of brain lesions in adrenoleukodystrophy (ALD) patients has shown that the lesions resemble those observed in MS patients. Because of this, researchers are exploring the potential benefit of vitamin D supplementation in ALD patients.
Vitamin D insufficiency and ALD
A study assessed the link between vitamin D levels, and brain and spinal cord demyelination in boys with ALD. Blood samples were obtained from young boys with ALD to measure their vitamin D levels. Cerebral demyelination was monitored using brain imaging.
Vitamin D is converted to 25-hydroxyvitamin D by the liver, so the researchers compared 25-hydroxyvitamin D levels in 8 boys with ALD who developed cerebral demyelination, with 8 boys who showed no myelin damage by the end of the follow-up period.
They found that vitamin D levels were significantly lower in the boys with ALD who later went on to develop cerebral demyelination compared with those with no demyelination.
The team concluded that although further detailed studies are required, low vitamin D levels may be a risk factor for childhood cerebral ALD (CALD).
Vitamin D in clinical trials for ALD
An ongoing Phase 1 study (NCT02595489) is testing the effect of two high doses of vitamin D3 on markers of oxidative stress and inflammation in the blood and brain of ALD patients. Vitamin D3 or cholecalciferol is one of the forms of vitamin D available as a dietary supplement, and it is the form that is made in the body through sun exposure.
The three-year pilot Stanford University study is recruiting 20 ALD patients, from 18 months to 25 years old. Patients will receive an oral dose of 2,000 international units (IU) of vitamin D3 daily for the first six months. Thereafter, the dose will increase to 4,000 IU daily for at least the next six months.
Blood samples will be collected every three months during the first year to measure 25-hydroxyvitamin D levels, monitor oxidative stress markers, and detect any toxicity issues associated with vitamin D intake. Previous studies have shown that damage to myelin sheath occurs due to oxidative stress caused by highly reactive molecules (free radicals). The Stanford pilot study will evaluate whether an increase in vitamin D3 levels can lower oxidative stress, justifying its use as a dietary supplement for patients with ALD.
Brain MRI will be performed every six months for the 36-month study period, especially for boys with ALD, ages 3 to 12. It will be used to identify cerebral involvement by checking for any abnormalities and lesions in the brain. Then vitamin D levels and brain MRIs will be compared to determine a possible correlation between the two.
The researchers hope to use the results for future large-scale studies assessing the use of vitamin D supplementation therapy in ALD patients.
Excessive use of vitamin D
Vitamin D is generally safe within the advised dosage limits, which is 4,000 IU maximum a day for adults, according to the National Institute of Health. Excessive use may cause side effects such as constipation, nausea, confusion, and weakness. Vitamin D is necessary for calcium uptake by the body, but taking too much of it may cause hypercalcemia — excessive calcium in the blood — which can result in kidney damage, irregular heart rhythms, and disorientation.
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