"Calcium supplementation should be accompanied by vitamin D, and vitamin D deficiency increases dementia risk" is a widely held belief, leading many to take additional vitamin D supplements. However, the causal relationship has not been fully validated by science. Research from the National Health Research Institutes (NHRI) reveals that vitamin D deficiency is not a cause of dementia but rather a consequence. Long-term high-dose vitamin D supplementation in older adults may actually increase dementia risk by 1.8 times, while in elderly individuals with dementia, it may raise mortality risk by 2.17 times.

Chih-Li Chuang, Deputy Director of the NHRI Institute of Molecular and Genomic Medicine, and Chih-Ching Hsu, Executive Director of the NHRI Center for Geriatric and Gerontology, analyzed National Health Insurance data. They found that among adults aged 65 and older without dementia, those who took prescription active vitamin D3 (calcitriol) for more than 146 days per year had a 1.8 times higher risk of developing dementia compared to non-users. For dementia patients who supplemented for over 146 days annually, the mortality risk was 2.17 times higher than non-users. These findings were published in 2021 and 2022 in the renowned aging research journal *Aging Cell*.

Chuang explained that mouse studies confirmed vitamin D does not play a protective role in dementia but instead contributes to "harmful processes (neuropathology)." He emphasized that this does not mean vitamin D is inherently bad but serves as a reminder for the public to reconsider its use—benefits come from proper timing, while excessive intake may have adverse effects.

The research team observed that under vitamin D-sufficient conditions, Alzheimer's disease (AD) mice had significantly lower blood vitamin D levels compared to wild-type mice. Surprisingly, in the brains of AD mice and postmortem AD patients (from the U.S. brain bank), vitamin D receptor (VDR) protein levels were "not reduced but increased," overlapping with amyloid plaques associated with neurodegeneration.

Chuang noted that despite vitamin D deficiency, VDR protein expression increased, indicating that vitamin D's original cellular mechanism is altered in AD. "Alzheimer's disease is the cause of low vitamin D levels, not the result of vitamin D deficiency."

Further research revealed that in healthy brains, VDR proteins enter the nucleus to perform neuroprotective gene transcription. However, in AD mice, VDR proteins bind with tumor suppressor protein p53 in the cytoplasm, promoting neuronal apoptosis.

While p53 is typically a beneficial protein that suppresses tumors, how can we prevent VDR from "going down the wrong path" with p53? Chuang explained that vitamin D has both beneficial and harmful pathways in the brain, with the harmful route potentially increasing with age. Inhibiting p53 could alleviate brain pathology, but continued vitamin D supplementation in AD mice worsened neurodegeneration and cognitive decline.

Beyond the mouse studies, Hsu's analysis of health insurance data from 14,648 dementia-free and 948 dementia-afflicted elderly individuals (2000–2010) yielded startling results.

The study found that those taking active vitamin D3 (calcitriol) for over 146 days per year (assuming 0.25 mcg/day, equivalent to 10 IU) had a 1.8 times higher dementia risk. For dementia patients, long-term supplementation increased mortality risk by 2.17 times.Hsu Chih-cheng stated that according to the National Health Insurance regulations, there are three conditions under which elderly individuals can be prescribed vitamin D3: "those with altered bone density due to hypothyroidism," "dialysis patients (dialysis-induced hormonal changes can also lead to hypothyroidism)," and "those with osteoporosis who have previously experienced fractures." Since the number of people in the first category is too small, this analysis only included the latter two.

"It should be noted that the above study only found a correlation and cannot prove causation," Hsu emphasized. Based on randomized controlled trials published in reputable international journals, no harm from vitamin D supplementation has been observed, but there is also no evidence that vitamin D can prevent dementia.

Hsu advised the elderly and dementia patients not to take high doses of vitamin D over the long term solely to prevent dementia. If supplementation is needed for other medical conditions but concerns about increasing dementia risk exist, he recommended discussing the pros and cons with their primary physician.

For children or young adults with a family history of dementia, is long-term vitamin D supplementation safe? Hsu explained that children's brains are still developing, which differs from the elderly. There is also more evidence supporting that adequate intake of vitamin D and calcium in children can prevent rickets and support normal growth. As for young people with a family history of dementia, whether long-term vitamin D supplementation is harmful requires further research.

Hsu reminded the public that vitamin D3 supplements are easily accessible—not just through health insurance prescriptions but also widely available for purchase. Those considering self-supplementation should pay attention to dosage and ideally consult a doctor first. Natural methods such as diet, exercise, and sun exposure can also help the body synthesize vitamin D and are less likely to lead to high-dose-related issues.

Source: https:/ / udn. com/ news/ story/ 7……dn- referralnews_ch2artbottom