Study: Supplements not impeded by abnormal vitamin D metabolism

Calcium, vitamin D can still compensate for low PTH in hypoparathyroidism

Joana Vindeirinho, PhD avatar

by Joana Vindeirinho, PhD |

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The use of calcium and vitamin D supplements to compensate for the low levels of parathyroid hormone (PTH) in hypoparathyroidism is not impeded by the abnormal vitamin D metabolism caused by the rare disease, a study reports.

People with hypoparathyroidism had higher levels of 25(OH)D, a marker of vitamin D levels, and calcitriol — the active form of vitamin D — than healthy individuals. They also were found to have increased production of the main inactive byproduct of vitamin D degradation.

Further, researchers found no differences in the levels of vitamin D byproducts between hypoparathyroidism patients who had adequate PTH compensation and those who did not.

Taken together, the results suggest that “the abnormality of vitamin D metabolism does not interfere with the achievement of hypoparathyroidism compensation” — and that the altered levels of vitamin D byproducts “might be a consequence of the received therapy and the pathophysiology [processes] of the disease,” the researchers wrote.

The study, “Parameters of Vitamin D Metabolism in Patients with Hypoparathyroidism,” was published in the journal Metabolites.

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Investigating vitamin D metabolism in the body

Hypoparathyroidism causes the body to have low levels of PTH, a hormone that regulates the levels of calcium, phosphorus, and vitamin D in the blood. Loss of PTH causes hypocalcemia, or low blood levels of calcium, which can lead to several symptoms, including fatigue, muscle spasms and cramps, and seizures.

Conventional hypoparathyroidism treatments include oral supplements of calcium and vitamin D.

In the body, the metabolism of vitamin D is done in three main steps. The first results in the formation of 25(OH)D by the CYP2R1 enzyme. In the second, the CYP27B1 enzyme converts 25(OH)D into calcitriol, a step that is stimulated by PTH. And finally, in the third step, the enzyme 24-hydroxylase degrades both 25(OH)D and calcitriol into inactive byproducts, removing them from the system.

Despite the importance of vitamin D in the disease and its treatment, few studies have assessed all the steps of vitamin D’s metabolism in people with hypoparathyroidism, according to a team of researchers from Moscow, Russia.

To fill this knowledge gap, the team evaluated biochemical parameters and vitamin D byproducts resulting from all three steps in blood serum samples of people with hypoparathyroidism. These were compared with samples from healthy individuals.

The study included 38 adults with hypoparathyroidism who had been treated at a single center between 2016 and 2022, and 38 healthy adults, who served as controls. Both groups were similar in age — with a median age of 48.8 in the control group and 49.6 in the patient group — and had a high proportion of women. There were 89.5% women in the patient group and 78.9% in the control group.

Hypoparathyroidism patients had a median disease duration of 61.5 months, and most were being treated with calcium (95%), alfacalcidol — an active vitamin D analog; 87% — and cholecalciferol (vitamin D3; 76%). Patients with blood calcium levels within 2.1–2.3 mmol/L and no symptoms of hypocalcemia were considered to have compensated hypoparathyroidism, whereas those who had abnormal calcium levels or symptoms of hypocalcemia were considered to have non-compensated disease.

Compared with the control group, serum samples of hypoparathyroidism patients had significantly lower concentrations of PTH, calcium, and magnesium, and significantly higher concentrations of phosphorus.

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Abnormal vitamin D metabolism not seen to interfere with compensation

In the assessment of vitamin D byproducts, the patient group had higher levels of 25(OH)D3 — including the variant form 3-epi-25(OH)D3 — calcitriol, and the inactive vitamin D byproduct (24,25(OH)2D3) compared with the control group. In fact, almost three-quarters of participants in the patient group maintained adequate 25(OH)D levels. Another difference between groups was the lower ratio of 25(OH)D3 to inactive product observed in the patient group.

Regarding the high levels of 25(OH)D, two mechanisms might be at play, the scientists noted: on the one hand, the low activity of PTH seen in hypoparathyroidism reduces the conversion of 25(OH)D into calcitriol. On the other, “due to the large amounts of active vitamin D, an increase in 24-hydroxylase activity might be expected, leading to the increased degradation of 25(OH)D3 in order to prevent toxicity,” the researchers wrote. This second hypothesis is supported by the higher concentrations of inactive byproducts and lower ratio of 25(OH)D3 to inactive product seen in the patient group.

Between the two subgroups of hypoparathyroidism, patients with non-compensated disease showed significantly lower concentrations of calcium, magnesium, and creatinine — a waste product from the normal wear and tear on muscles — than those of patients with compensated hypoparathyroidism. However, no differences were found between subgroups in the concentration of vitamin D byproducts.

“Thus, we assume that the abnormality of vitamin D metabolism does not interfere with the achievement of hypoparathyroidism compensation,” the research team wrote.

According to the investigators, although the study had several strengths, such as the use of a control group, it was still limited by the small size and high proportion of women in the groups.

“To the best of the authors’ knowledge, this is the first cohort study to evaluate the process of vitamin D inactivation in hypoparathyroidism, and the results should be confirmed in further studies with the assessment of a wider range of metabolites in large samples,” the researchers concluded.