Does Vitamin D Aggravate Dementia? New Research Faces 2 Controversies

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Vitamin D is a health supplement that many people take regularly, but a recent study found that one type of vitamin D may exacerbate Alzheimer’s disease. In light of this finding, how should we supplement vitamin D correctly?

Alzheimer’s disease (AD) has complex mechanisms, of which much is still unknown.

For instance, vitamin D deficiency has been found in Alzheimer’s patients. So, is their insufficient intake of vitamin D causing AD? A recent Taiwanese study published in the journal Aging Cell suggests that a low level of vitamin D is a consequence of AD, and that supplementation of vitamin D may even exacerbate the disease.

The Taiwanese researchers fed AD mice (transgenic mice) a diet containing sufficient vitamin D3 (cholecalciferol), or a D3-supplemented diet, and the animals subsequently showed significantly lower levels of serum vitamin D, and their AD worsened more quickly than in the control group.

Besides animal models, the scientists also conducted a large-scale analysis of data from Taiwan’s National Health Insurance Research Database (NHIRD). Their findings included:

• Dementia-free adults 65 years or older taking active vitamin D3 supplements (calcitriol) for over 146 days per year were 1.8 times more likely to develop dementia than those not taking the supplements.
• Dementia patients taking active vitamin D3 supplements over the long term had 2.17 times the risk of mortality than those not taking the supplements.

The report researchers warn that AD patients should not use vitamin D supplements for a prolonged period.

However, this research raises two important points that must be considered:

1. Active vitamin D3, calcitriol, should not be equated with inactive vitamin D supplements

The vitamin D that people obtain from basking in the sun, consuming food, and taking supplements is an inactive vitamin D called cholecalciferol. It must first be converted into calcifediol in the liver before being metabolized by the kidneys to become the active vitamin D, calcitriol.

Calcitriol was used in the study of the older AD patients. It is commonly used by patients with kidney diseases, parathyroid diseases, rickets, and severe osteoporosis.

“To endocrinology, calcitriol and inactive vitamin D are two completely different things, and we will never think that taking active vitamin D is supplementing inactive vitamin D,” said Dr. Chieh-Li Wang, a hemodialysis physician and director of the Bo-An Dialysis Clinic in Taiwan.

He pointed out that inactive vitamin D needs to be metabolized by the liver and kidneys to become effective. And the human body has precise regulation: When the body’s demand for vitamin D is high, it will be converted into calcitriol quickly and rapidly metabolized.

The blood test for serum vitamin D refers to calcifediol, not calcitriol, because calcifediol has the longest half-life in the body and its inventory is the best indicator of vitamin D deficiency.

Dr. Wang said that if people with insufficient vitamin D in the body are given active calcitriol, their blood test results will still show vitamin D deficiency.

2. Patients who need to take calcitriol are also at high risk of Alzheimer’s disease

This study did not observe real-world patients, but instead analyzed Taiwan’s health insurance database, which has its limitations and blind spots.

Dr. Shih-Heng Chang, director of Precise Holistic Medical Clinic in Taipei, Taiwan, observed that the database shows that patients taking calcitriol have a higher chance of being diagnosed with Alzheimer’s disease in the future. However, their AD is not necessarily caused by calcitriol; the patients’ own chronic diseases could also be the cause.

For example, people with kidney diseases often need to take calcitriol to treat their thyroid problems. Dr. Chih-Hao Lin, director of the Department of Neurosurgery of Lin Shin Hospital in Taiwan, said that patients with kidney diseases are prone to dementia due to poor circulation and strokes caused by vascular problems. People with kidney diseases may also suffer from diabetes and high blood pressure, which are also risk factors for dementia.

At the same time, due to their illness, chronic disease patients who take calcitriol often tend to have a low level of physical and social activity, or poor sleep quality, which are also risk factors for dementia.

The database used for the study only records the use of calcitriol, but does not have data on inactive vitamin D; it doesn’t show a correlation between inactive vitamin D intake and Alzheimer’s disease.

Dr. Chang said that although animal experiments have shown that inactive vitamin D intake could worsen dementia, there is a gap between animals and humans. “There are results observed in animals that are actually not seen in humans,” he said.

Is Vitamin D Supplementation Good or Bad for Alzheimer’s Disease?

There has been much research on the relationship between vitamin D and Alzheimer’s disease. A 2021 study by Harvard Medical School concluded that inactive vitamin D supplementation was not associated with cognitive decline.

The researchers asked the participants, aged 60 years and older, and free of cardiovascular disease and cancer, to take vitamin D3 (2,000 IU of cholecalciferol) every day. The researchers then performed cognitive assessments by phone or in person. As it turned out, over a period of two to three years, generally well-educated participants’ supplementation of vitamin D3 was unrelated to their cognitive decline; no correlated effects were observed in their verbal memory, executive functioning, attention, and overall cognitive functions.

However, a slight cognitive benefit of vitamin D3 supplementation was observed in older Black individuals.

Another study over 7.8 years with over 4,000 participants discovered that after an intake of 400 IU of vitamin D3 and 1,000 mg of calcium per day, no association was observed between the supplementation and cognitive impairment or dementia.

Some People Need Vitamin D Supplements

Active vitamin D (calcitriol) as a medicine can be used for the treatment of hypocalcemia, osteoporosis, rickets, osteomalacia, and psoriasis. Dialysis patients and chronic kidney disease patients need calcitriol to control their hypocalcemia and thyroid problems.

Each medicine has its side effects, and calcitriol may, in fact, cause hypercalcemia, the increased calcification of blood vessels or tissues. Dr. Wang cautioned that patients on calcitriol should not stop taking the medicine without their doctor’s approval.

Absorbing sunlight and consuming certain foods are the best way to supplement the body if it’s deficient in inactive vitamin D. According to Dr. Chang, we shouldn’t shy away from the supplement because of the study results. The human body cannot live without vitamin D—a very important hormone essential to our bones, muscles, and many of our organs and physiological systems.

For instance, vitamin D promotes calcium absorption in the intestines. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts. Without sufficient vitamin D, our bones can become thin, brittle, or deformed.

The normal development and growth of our muscles also requires vitamin D. Inadequate vitamin D levels in the body can adversely affect muscle strength and lead to muscle weakness and pain.

Vitamin D also plays other roles in the body, including reduction of inflammation and regulation of cell growth, and is essential to neuromuscular and immune function and glucose metabolism.

Some people are especially at risk for vitamin D deficiency, especially those who stay indoors for long periods with little sunlight exposure and elderly people who are less active. The ability of the skin to synthesize vitamin D decreases with age in the elderly.

In addition to getting vitamin D from food, people can also use health supplements, because natural foods contain little vitamin D. Food and supplements contain two main forms of vitamin D: vitamin D2 from plant sources and vitamin D3 from animal sources. Vegetarians can opt for vitamin D2.

According to Dr. Chang, it is dangerous if the concentration of vitamin D in the body is too low, and it doesn’t bring additional benefit if it is too high. Therefore, vitamin D can be supplemented in moderation. The average person supplements about 500 IU a day, but people who are less exposed to the sun can supplement 1,000 to 2,000 IU per day.