Health Benefits of Vitamin D and Sunlight - Cognitive Benefits

Link between vitamin D, dementia risk confirmed

Adults in a recent study who were moderately deficient in vitamin D had a 53 per cent increased risk of developing dementia of any kind, and the risk increased to 125 per cent in those who were severely deficient. Vitamin D deficiency is associated with a substantially increased risk of dementia and Alzheimer's disease in older people, according to the most robust study of its kind ever conducted.


An international team found that study participants who were severely Vitamin D deficient were more than twice as likely to develop dementia and Alzheimer's disease.

The team studied elderly Americans who took part in the Cardiovascular Health Study. They discovered that adults in the study who were moderately deficient in vitamin D had a 53 per cent increased risk of developing dementia of any kind, and the risk increased to 125 per cent in those who were severely deficient.

Similar results were recorded for Alzheimer's disease, with the moderately deficient group 69 per cent more likely to develop this type of dementia, jumping to a 122 per cent increased risk for those severely deficient.

The study was published in Neurology, the medical journal of the American Academy of Neurology. It looked at 1,658 adults aged 65 and over, who were able to walk unaided and were free from dementia, cardiovascular disease and stroke at the start of the study. The participants were then followed for six years to investigate who went on to develop Alzheimer's disease and other forms of dementia.

The researchers expected to find an association between low Vitamin D levels and the risk of dementia and Alzheimer's disease, but the results were surprising -- they actually found that the association was twice as strong as anticipated.

Increasing evidence of an association between low vitamin D levels and cognitive decline

Vitamin D deficiency and cognitive impairment are common in older adults, but there isn't a lot of conclusive research into whether there's a relationship between the two.

A new study from Wake Forest Baptist Medical Center published online ahead of print this month in the Journal of the American Geriatrics Society enhances the existing literature on the subject.

"This study provides increasing evidence that suggests there is an association between low vitamin D levels and cognitive decline over time," said lead author Valerie Wilson, M.D., assistant professor of geriatrics at Wake Forest Baptist. "Although this study cannot establish a direct cause and effect relationship, it would have a huge public health implication if vitamin D supplementation could be shown to improve cognitive performance over time because deficiency is so common in the population."

Wilson and colleagues were interested in the association between vitamin D levels and cognitive function over time in older adults. They used data from the Health, Aging and Body composition (Health ABC) study to look at the relationship. The researchers looked at 2,777 well-functioning adults aged 70 to 79 whose cognitive function was measured at the study's onset and again four years later. Vitamin D levels were measured at the 12-month follow-up visit.

The Health ABC study cohort consists of 3,075 Medicare-eligible, white and black, well-functioning, community-dwelling older adults who were recruited between April 1997 and June 1998 from Pittsburgh, Pa., and Memphis, Tenn.

"With just the baseline observational data, you can't conclude that low vitamin D causes cognitive decline. When we looked four years down the road, low vitamin D was associated with worse cognitive performance on one of the two cognitive tests used," Wilson said. "It is interesting that there is this association and ultimately the next question is whether or not supplementing vitamin D would improve cognitive function over time."

Wilson said randomized, controlled trials are needed to determine whether vitamin D supplementation can prevent cognitive decline and definitively establish a causal relationship.

"Doctors need this information to make well-supported recommendations to their patients," Wilson said. "Further research is also needed to evaluate whether specific cognitive domains, such as memory versus concentration, are especially sensitive to low vitamin D levels."

Vitamin D may help clear amyloid plaques found in Alzheimer's

A team of academic researchers has identified the intracellular mechanisms regulated by vitamin D3 that may help the body clear the brain of amyloid beta, the main component of plaques associated with Alzheimer's disease.

Published in the March 6, 2012 issue of the Journal of Alzheimer's Disease, the early findings show that vitamin D3 may activate key genes and cellular signaling networks to help stimulate the immune system to clear the amyloid-beta protein.

Previous laboratory work by the team demonstrated that specific types of immune cells in Alzheimer's patients may respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, by stimulating the innate immune system to clear amyloid beta. But the researchers didn't know how it worked.

"This new study helped clarify the key mechanisms involved, which will help us better understand the usefulness of vitamin D3 and curcumin as possible therapies for Alzheimer's disease," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.

For the study, scientists drew blood samples from Alzheimer's patients and healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for gobbling up amyloid beta and other waste products in the brain and body.

The team incubated the immune cells overnight with amyloid beta. An active form of vitamin D3 called 1a,25–dihydroxyvitamin D3, which is made in the body by enzymatic conversion in the liver and kidneys, was added to some of the cells to gauge the effect it had on amyloid beta absorption.

Previous work by the team, based on the function of Alzheimer's patients' macrophages, showed that there are at least two types of patients and macrophages: Type I macrophages are improved by addition of 1a,25–dihydroxyvitamin D3 and curcuminoids (a synthetic form of curcumin), while Type II macrophages are improved only by adding 1a,25–dihydroxyvitamin D3.

Researchers found that in both Type I and Type II macrophages, the added 1a,25–dihydroxyvitamin D3 played a key role in opening a specific chloride channel called "chloride channel 3 (CLC3)," which is important in supporting the uptake of amyloid beta through the process known as phagocytosis. Curcuminoids activated this chloride channel only in Type I macrophages.

The scientists also found that 1a,25–dihydroxyvitamin D3 strongly helped trigger the genetic transcription of the chloride channel and the receptor for 1a,25–dihydroxyvitamin D3 in Type II macrophages. Transcription is the first step leading to gene expression.

The mechanisms behind the effects of 1a,25–dihydroxyvitamin D3 on phagocytosis were complex and dependent on calcium and signaling by the "MAPK" pathway, which helps communicate a signal from the vitamin D3 receptor located on the surface of a cell to the DNA in the cell's nucleus.

The pivotal effect of 1a,25–dihydroxyvitamin D3 was shown in a collaboration between Dr. Patrick R. Griffin from the Scripps Research Institute and Dr. Mathew T. Mizwicki from UC Riverside. They utilized a technique based on mass spectrometry, which showed that 1a,25–dihydroxyvitamin D3 stabilized many more critical sites on the vitamin D receptor than did the curcuminoids.

"Our findings demonstrate that active forms of vitamin D3 may be an important regulator of immune activities of macrophages in helping to clear amyloid plaques by directly regulating the expression of genes, as well as the structural physical workings of the cells," said study author Mizwicki, who was an assistant research biochemist in the department of biochemistry at UC Riverside when the study was conducted.

According to the team, one of the next stages of research would be a clinical trial with vitamin D3 to assess the impact on Alzheimer's disease patients. Previous studies by other teams have shown that a low serum level of 25–hydroxyvitamin D3 may be associated with cognitive decline. It is too early to recommend a definitive dosage of vitamin D3 to help with Alzheimer's disease and brain health, the researchers said. They add that ongoing studies are showing that vitamin D3 may be beneficial in reducing the incidence of a growing number of human diseases.

Vitamin D Tied to Women's Cognitive Performance

Two new studies appearing in the Journals of Gerontology Series A: Biological Sciences and Medical Sciences show that vitamin D may be a vital component for the cognitive health of women as they age.

Higher vitamin D dietary intake is associated with a lower risk of developing Alzheimer's disease, according to research conducted by a team led by Cedric Annweiler, MD, PhD, at the Angers University Hospital in France.

Similarly, investigators led by Yelena Slinin, MD, MS, at the VA Medical Center in Minneapolis found that low vitamin D levels among older women are associated with higher odds of global cognitive impairment and a higher risk of global cognitive decline.

Slinin's group based its analysis on 6,257 community-dwelling older women who had vitamin D levels measured during the Study of Osteopathic Fractures and whose cognitive function was tested by the Mini-Mental State Examination and/or Trail Making Test Part B.

Very low levels of vitamin D (less than 10 nanograms per milliliter of blood serum) among older women were associated with higher odds of global cognitive impairment at baseline, and low vitamin D levels (less than 20 nanograms per milliliter) among cognitively-impaired women were associated with a higher risk of incident global cognitive decline, as measured by performance on the Mini-Mental State Examination.

Annweieler's team's findings were based on data from 498 community-dwelling women who participated in the Toulouse cohort of the Epidemiology of Osteoporosis study.

Among this population, women who developed Alzheimer's disease had lower baseline vitamin D intakes (an average of 50.3 micrograms per week) than those who developed other dementias (an average of 63.6 micrograms per week) or no dementia at all (an average of 59.0 micrograms per week).

These reports follow an article published in the Journals of Gerontology Series A earlier this year that found that both men and women who don't get enough vitamin D -- either from diet, supplements, or sun exposure -- may be at increased risk of developing mobility limitations and disability.

Low vitamin D levels associated with cognitive decline

Older adults with low levels of vitamin D appear more likely to experience declines in thinking, learning and memory over a six-year period, according to a report in the July 12, 2010 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

An estimated 40 percent to 100 percent of older adults in the United States and Europe are deficient in vitamin D, according to background information in the article. This deficiency has been linked to fractures, various chronic diseases and death. Vitamin D may help prevent the degeneration of brain tissue by having a role in formation of nervous tissue, maintaining levels of calcium in the body, or clearing of beta-amyloid, the substance that forms the brain plaques and tangles associated with Alzheimer's disease.

David J. Llewellyn, Ph.D., of University of Exeter, England, and colleagues assessed blood levels of vitamin D in 858 adults who were age 65 or older when the study began in 1998. Participants completed interviews and medical examinations and provided blood samples. At the beginning of the study and again after three and six years, they repeated three tests of cognitive function—one assessing overall cognition, one focusing on attention and one that places greater emphasis on executive function, or the ability to plan, organize and prioritize.

Participants who were severely deficient in vitamin D (having blood levels of 25-hydroxyvitamin D of less than 25 nanomoles per liter) were 60 percent more likely to have substantial cognitive decline in general over the six-year period and 31 percent more likely to experience declines on the test measuring executive function than those with sufficient vitamin D levels. "The association remained significant after adjustment for a wide range of potential confounders and when analyses were restricted to elderly subjects who were non-demented at baseline," the authors write. However, no significant association was seen for the test measuring attention.

"If future prospective studies and randomized controlled trials confirm that vitamin D deficiency is causally related to cognitive decline, then this would open up important new possibilities for treatment and prevention," the authors conclude.

Vitamin D Promotes Mental Agility in Elders

At a time when consumer interest in health-enhancing foods is high, Agricultural Research Service (ARS)-funded scientists have contributed to a limited but growing body of evidence of a link between vitamin D and cognitive function.

Cognitive function is measured by the level at which the brain is able to manage and use available information for activities of daily life. Alzheimer's disease, the most common form of age-related dementia, affects about 47 percent of adults aged 85 years or older in the United States. Identifying nutritional factors that lower cognitive dysfunction and help preserve independent living provides economic and public health benefits, according to authors.

Metabolic pathways for vitamin D have been found in the hippocampus and cerebellum areas of the brain involved in planning, processing, and forming new memories. This suggests that vitamin D may be implicated in cognitive processes.

The study involved more than 1,000 participants receiving home care. The researchers evaluated associations between measured vitamin D blood concentrations and neuropsychological tests. Elders requiring home care have a higher risk of not getting enough vitamin D because of limited sunlight exposure and other factors.

The participants, ages 65 to 99 years, were grouped by their vitamin D status, which was categorized as deficient, insufficient, or sufficient. Only 35 percent had sufficient vitamin D blood levels. They had better cognitive performance on the tests than those in the deficient and insufficient categories, particularly on measures of "executive performance," such as cognitive flexibility, perceptual complexity, and reasoning. The associations persisted after taking into consideration other variables that could also affect cognitive performance.

Lack of 'Sunshine vitamin' linked to cognitive problems in older people

Researchers from the Peninsula Medical School, the University of Cambridge and the University of Michigan, have for the first time identified a relationship between Vitamin D, the "sunshine vitamin", and cognitive impairment in a large-scale study of older people. The importance of these findings lies in the connection between cognitive function and dementia: people who have impaired cognitive function are more likely to develop dementia. The paper appeared in the Journal of Geriatric Psychology and Neurology.

The study was based on data on almost 2000 adults aged 65 and over who participated in the Health Survey for England in 2000 and whose levels of cognitive function were assessed. The study found that as levels of Vitamin D went down, levels of cognitive impairment went up. Compared to those with optimum levels of Vitamin D, those with the lowest levels were more than twice as likely to be cognitively impaired.

Vitamin D is important in maintaining bone health, in the absorption of calcium and phosphorus, and in helping our immune system. In humans, Vitamin D comes from three main sources – exposure to sunlight, foods such as oily fish, and foods that are fortified with vitamin D (such as milk, cereals, and soya drinks). One problem faced by older people is that the capacity of the skin to absorb Vitamin D from sunlight decreases as the body ages, so they are more reliant on obtaining Vitamin D from other sources.

According to the Alzheimer's Society, dementia affects 700,000 people in the UK and it is predicted that this figure will rise to over 1 million by 2025. Two-thirds of sufferers are women, and 60,000 deaths a year are attributable to the condition. It is believed that the financial cost of dementia to the UK is over £17 billion a year.

Dr. Iain Lang from the Peninsula Medical School, who worked on the study, commented: "This is the first large-scale study to identify a relationship between Vitamin D and cognitive impairment in later life. Dementia is a growing problem for health services everywhere, and people who have cognitive impairment are at higher risk of going on to develop dementia. That means identifying ways in which we can reduce levels of dementia is a key challenge for health services."

Dr Lang added: "For those of us who live in countries where there are dark winters without much sunlight, like the UK, getting enough Vitamin D can be a real problem – particularly for older people, who absorb less Vitamin D from sunlight. One way to address this might be to provide older adults with Vitamin D supplements. This has been proposed in the past as a way of improving bone health in older people, but our results suggest it might also have other benefits. We need to investigate whether vitamin D supplementation is a cost-effective and low-risk way of reducing older people's risks of developing cognitive impairment and dementia."

Vitamin D, Omega-3 May Help Clear Amyloid Plaques Found in Alzheimer's

A team of academic researchers has pinpointed how vitamin D3 and omega-3 fatty acids may enhance the immune system's ability to clear the brain of amyloid plaques, one of the hallmarks of Alzheimer's disease.

In a small pilot study published in the Feb. 5, 2013 issue of the Journal of Alzheimer's Disease, the scientists identified key genes and signaling networks regulated by vitamin D3 and the omega-3 fatty acid DHA (docosahexaenoic acid) that may help control inflammation and improve plaque clearance.

Previous laboratory work by the team helped clarify key mechanisms involved in helping vitamin D3 clear amyloid-beta, the abnormal protein found in the plaque. The new study extends the previous findings with vitamin D3 and highlights the role of omega-3 DHA.

"Our new study sheds further light on a possible role for nutritional substances such as vitamin D3 and omega-3 in boosting immunity to help fight Alzheimer's," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA.

For the study, scientists drew blood samples from both Alzheimer's patients and healthy controls, then isolated critical immune cells called macrophages from the blood. Macrophages are responsible for gobbling up amyloid-beta and other waste products in the brain and body.

The team incubated the immune cells overnight with amyloid-beta. They added either an active form of vitamin D3 called 1alpha,25–dihydroxyvitamin D3 or an active form of the omega-3 fatty acid DHA called resolvin D1 to some of the cells to gauge the effect they had on inflammation and amyloid-beta absorption.

Both 1alpha, 25-dihydroxyvitamin D3 and resolvin D1 improved the ability of the Alzheimer's disease patients' macrophages to gobble-up amyloid-beta, and they inhibited the cell death that is induced by amyloid-beta. Researchers observed that each nutrition molecule utilized different receptors and common signaling pathways to do this.

Previous work by the team, based on the function of Alzheimer's patients' macrophages, showed that there are two groups of patients and macrophages. In the current study, researchers found that the macrophages of the Alzheimer's patients differentially expressed inflammatory genes, compared with the healthy controls, and that two distinct transcription patterns were found that further define the two groups: Group 1 had an increased transcription of inflammatory genes, while Group 2 had decreased transcription. Transcription is the first step leading to gene expression.

"Further study may help us identify if these two distinct transcription patterns of inflammatory genes could possibly distinguish either two stages or two types of Alzheimer's disease," said study author Mathew Mizwicki, an assistant researcher at the David Geffen School of Medicine at UCLA.

While researchers found that 1alpha,25-dihydroxyvitamin D3 and resolvin D1 greatly improved the clearance of amyloid-beta by macrophages in patients in both groups, they discovered subtleties in the effects the two substances had on the expression of inflammatory genes in the two groups. In Group 1, the increased-inflammation group, macrophages showed a decrease of inflammatory activation; in Group 2, macrophages showed an increase of the inflammatory genes IL1 and TLRs when either 1alpha,25-Dihydroxyvitamin D3 or resolvin D1 were added.

More study is needed, Fiala said, but these differences could be associated with the severity of patients' nutritional and/or metabolic deficiencies of vitamin D3 and DHA, as well as the omega-3 fatty acid EPA (eicosapentaenoic acid).

"We may find that we need to carefully balance the supplementation with vitamin D3 and omega-3 fatty acids, depending on each patient in order to help promote efficient clearing of amyloid-beta," Fiala said. "This is a first step in understanding what form and in which patients these nutrition substances might work best."

According to Fiala, an active (not oxidized) form of omega-3 DHA, which is the precursor of the resolvin D1 used in this study, may work better than more commercially available forms of DHA, which generally are not protected against the oxidation that can render a molecule inactive.