Vitamin D and Emerging Science: Cellular Aging and Cognitive Health

April 6, 2017
Irfan Qureshi
Volume 20, Issue 3

Two unique areas of science are emerging around vitamin D: healthy cellular aging and cognitive health.

Vitamin D is rightly regarded for its crucial role in supporting healthy bones, but its influence extends far beyond the skeletal system. As a regulator of gene expression for more than 3% of the human genome, vitamin D’s extraskeletal (acting outside of the skeletal system) potential is vast. This hormone-like vitamin is involved in a wide array of biological functions, including immune health, cardiovascular function, metabolic balance, muscle strength, and blood sugar metabolism.1

A plethora of research is showing that vitamin D participates in multiple aspects of cellular metabolism and cellular differentiation. Its influence on immune function extends to the innate and adaptive immune system, and it also has anti-inflammatory effects. In the area of cardiovascular health, numerous studies point to an increased risk of cardiovascular events with lower vitamin D levels. Similarly, elevated vitamin D levels decrease the likelihood of hypertension.2

Two unique areas of emerging science surrounding vitamin D include aging and cognitive health. As additional research is conducted in these areas, it is becoming clear that vitamin D plays a significant role in keeping cells healthy, vital, and youthful, as well as in maintaining brain function with advancing age.

 

Vitamin D and Aging

Telomeres are end caps on chromosomes that have received increased attention over the years because of their association with cellular aging and their relationship to the development of age-associated chronic conditions. In general, longer telomere length is associated with a reduced risk of chronic conditions and better cellular health. Thus, telomere length may be a potential marker of biologic aging. Telomere dysfunction in cells occurs for several reasons and is often a result of the aging process itself.3 Cardiovascular disease and diabetes, among others conditions, are characterized by an increased rate of telomere shortening, which indicates an increased effect of these disease conditions on the aging of the body.4

Vitamin D insufficiency has been linked to the onset and prevalence of numerous chronic health issues, and it is well-known that vitamin D impacts many aspects of cellular aging through its influence on various aspects of cellular metabolism. In many studies, researchers have found vitamin D to be associated with telomere length, a possible explanation for vitamin D’s potential role in delaying cellular aging.4

A newly published study led by Mohsen Mazidi of the Chinese Academy of Sciences (Beijing, China) evaluated telomere length in association with serum levels of 25-hydroxyvitamin D in participants of the National Health and Nutrition Examination Survey (NHANES).5 The study sample included 4,347 participants with an average age of 42.7 years. The authors found that for each increment increase in serum 25-hydroxyvitamin D levels (25(OH)D; a common measure of vitamin D status), there was a corresponding increase in telomere-to-single-copy gene ratio, a measure of telomere length, in both women and men. After adjusting for smoking status, BMI, and physical activity levels, however, the significant relationship went away. Despite the presence of confounding factors, the authors concluded that serum levels of vitamin D had a possible positive association with telomere length in this sample, which should be investigated further.

Taking the previous analysis a step further, researchers from Harvard Medical School (Boston, MA) and the University of Tromsoe–The Arctic University of Norway (Tromsoe, Norway) also used NHANES data from 2001-2002 and stratified their analysis of telomere length by age, dividing the subjects into young adults (age 20-39), middle age (40-59), and older age (greater than 60) segments.6 Measuring leukocyte telomere length via polymerase chain reaction techniques, the investigators found that middle-aged adults with 25(OH)D concentrations above 50 nmol/L had significantly longer telomeres than those with levels below 50 nmol/L, further suggesting genomic instability in those with lower levels of vitamin D. An earlier analysis conducted by Jason Liu and colleagues from the Harvard School of Public Health (Boston, MA) looked at participants from the Nurses’ Health Study.7 Included in the analysis were 1,424 participants who had plasma samples taken in 1989–1990. The researchers found that higher serum levels of 25-hydroxyvitamin D were significantly associated with longer telomere length. 

While the studies highlighted above indicate that vitamin D concentrations are associated with positive benefits for telomeres, a previous study assessed the impact of vitamin D supplementation on telomerase activity in African American participants. Telomerase is an essential enzyme that functions to maintain telomere length. Led by Haidong Zhu of Georgia Health Sciences University (Augusta, GA), this four-month double-blind placebo-controlled study enrolled 57 healthy African American men and women.8 Each month, participants were supplemented with 60,000 IU vitamin D3 or a placebo. As plasma 25(OH)D levels increased substantially in the supplementation group from baseline to the end of the four-month period, telomerase activity significantly increased by an average of 19%. This remained unchanged from baseline in the placebo group, indicating that vitamin D supplementation could support the function of this important enzyme in the study population. 

These studies suggest that vitamin D is an important nutrient for healthy cellular aging. Higher levels of vitamin D may, therefore, have a protective effect on cellular health and have implications for aging as well as prevention of several chronic conditions.

Vitamin D and Cognitive Health

Vitamin D plays an important role in normal brain functioning by acting on several processes relevant to brain health. Some of these mechanisms include its ability to influence neural transmission, neurogenesis, preventing neuronal death, and clearing amyloid proteins.9 Additionally, vitamin D likely has antioxidant and anti-inflammatory activity in brain tissue, which supports against degenerative processes.10

Several studies have attempted to clarify the relationship between vitamin D and cognitive function as well as vitamin D’s role in the development of dementia. The findings have been mixed. A newly published meta-analysis conducted by researchers in Austria looked at the potential role of vitamin D deficiency as a risk factor for dementia.11 Evaluating studies published between 1990 and 2015, the researchers identified five cohort studies looking at dementia risk in relation to vitamin D deficiency. The meta-analysis showed that those individuals with 25(OH)D levels below 25 nmol/L had significantly higher risk of dementia than those with levels greater than 50 nmol/L. While this was an interesting finding, the authors cautioned that the strength of the evidence is weak since the studies were only of an observational nature. Furthermore, in a cohort of 1,182 Swedish men with an average age of 71, after 18 years of follow-up, researchers found no association between serum vitamin D levels or vitamin D intake with long-term risk of dementia or cognitive impairment.12

Vitamin D has, however, recently been found to positively influence a physiological process that may be important for prevention of Alzheimer’s disease. Brendan Miller and colleagues from Arizona State University (Phoenix, AZ) conducted a randomized pilot study in which they examined the effect of vitamin D supplementation (50,000 IU/wk) for eight weeks on levels of amyloid-β protein, low plasma levels (and elevated brain levels) of which are linked to Alzheimer’s disease.13 In this small study (average age of 64), researchers found that vitamin D supplementation increased plasma amyloid-β levels, suggesting decreased brain levels of this protein.

Additional studies, including those assessing the effects of vitamin D supplementation, have shown cognitive benefit. In a randomized trial led by Jacqueline Pettersen at the University of British Columbia (Vancouver, Canada), researchers included 82 healthy adults with insufficient vitamin D levels (<75 nmol/L) to assess the effect of a low dose (400 IU/d) versus a high dose (4,000 IU/d) of vitamin D3.14 Over the course of the 18-week study, researchers assessed cognitive performance using standardized tests of cognitive function. Significant improvements were noted on a pattern-recognition memory task as well as the paired associates learning task (assessments of visual memory) in the high-dose vitamin D group. No similar changes were noted in the low-dose group. Measures of verbal memory did not change in either group. 

In another study, the same group of researchers evaluated the relationship between serum levels of vitamin D and executive functioning in 142 healthy adults.15 They stratified individuals at baseline into four groups based on vitamin D status: insufficient (<50 nmol/L), low sufficient (50 to 75 nmol/L), high sufficient (75 to 100 nmol/L), and supra-therapeutic (≥100 nmol/L). After assessing the subjects following four tasks of executive functioning, they found that those in the supra-therapeutic vitamin D group performed significantly better on verbal memory tasks than participants with lower serum levels of vitamin D. The authors proffer that higher levels of vitamin D, beyond those deemed sufficient for bone health, may be needed to achieve optimal benefits for cognitive function.

Researchers from Rutgers University (New Brunswick, NJ) and University of California, Davis (Davis, CA), recently conducted a longitudinal study in an ethnically diverse cohort to examine the association between vitamin D status and cognitive decline.16 In the study, 382 older adults with a mean age of 75.5 were followed for an average of 4.8 years. In addition to white individuals, the study included African American, Hispanic, and a small percentage of other ethnicities. Vitamin D levels were assessed at baseline and at yearly follow-up visits. The average baseline serum 25(OH)D concentration was 19.2 ng/mL (47.9 nmol/L), with 26% of the participants classified as vitamin D–deficient and 35% insufficient. Nearly 50% of the participants were classified as cognitively normal at baseline, while 33% had mild cognitive impairment and 17% had a diagnosis of dementia. At the end of the study, the researchers found that the rate of decline in executive function and episodic memory in vitamin D–deficient and insufficient groups significantly exceeded the decline in those with adequate vitamin D status. These results as well as others point to the potential significance of vitamin D in supporting healthy cognitive function with age and lend support to the possible ability of the vitamin to reduce the risk of cognitive disease.

 

Scratching the Surface

As a vitamin that functions more like a hormone and influences a broad range of physiological processes, vitamin D’s necessity for health is quite evident. Research continues to shed light on the potential actions of this unique vitamin. 

Given research indicating widespread insufficiencies in a large segment of the population coupled with potential therapeutic effects of sustaining higher levels, ensuring an adequate intake of vitamin D may be good insurance to support the body and brain against the inevitable effects of aging.

 

Also read:

2016 Vitamin Science Update

Vitamin D Defends Against Acute Respiratory Tract Infections?

Vitamin D Deficiency Associated with Low BMD in Women with Hyperparathyroidism

 

 

References:

  1. Caprio M et al., “Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects,” Eating and Weight Disorders, vol. 22, no. 1 (March 2017): 27–41
  2. Christakos S et al., “Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects,” Physiological Reviews, vol. 96, no. 1 (January 2016): 365–408
  3. Nilsson PM et al., “Telomeres and cardiovascular disease risk: an update 2013,” Translational Research: The Journal of Laboratory and Clinical Medicine, vol. 162, no. 6 (December 2013): 371–380 
  4. Pusceddu I et al., “The role of telomeres and vitamin D in cellular aging and age-related diseases,” Clinical Chemistry and Laboratory Medicine, vol. 53, no. 11 (October 2015): 1661–1678 
  5. Mazidi M et al., “The association of telomere length and serum 25-hydroxyvitamin D levels in US adults: the National Health and Nutrition Examination Survey,” Archives of Medical Science, vol. 13, no. 1 (February 1, 2017): 61–65
  6. Beilfuss J et al., “Serum 25-hydroxyvitamin D has a modest positive association with leukocyte telomere length in middle-aged US adults,” The Journal of Nutrition. Published online February 8, 2017.
  7. Liu JJ et al., “Plasma vitamin D biomarkers and leukocyte telomere length,” American Journal of Epidemiology, vol. 177, no. 12 (June 15, 2013): 1411–1417
  8. Zhu H et al., “Increased telomerase activity and vitamin D supplementation in overweight African Americans,” International Journal of Obesity, vol. 36, no. 6 (June 2012) 805–809
  9. Brouwer-Brolsma EM et al., “Vitamin D and cognition in older adults: an update of recent findings,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 18, no. 1 (January 2015) 11–16
  10. Annweiler C., “Vitamin D in dementia prevention,” Annals of the New York Academy of Sciences, vol. 1367, no. 1 (March 2016): 57–63 
  11. Sommer I et al., “Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis,” BMC Geriatrics, vol. 17, no. 1 (January 13, 2017): 16
  12. Olsson E et al., “Vitamin D is not associated with incident dementia or cognitive impairment: an 18-y follow-up study in community-living old men,” American Journal of Clinical Nutrition. Published online February 15, 2017.
  13. Miller BJ et al., “Vitamin D supplementation appears to increase plasma Aβ40 in vitamin D insufficient older adults: a pilot randomized controlled trial,” Journal of Alzheimer’s Disease, vol. 52, no. 3 (March 2016): 843–847 
  14. Pettersen JA et al., “Does high dose vitamin D supplementation enhance cognition?: a randomized trial in healthy adults,” Experimental Gerontology. Published online February 4, 2017.
  15. Pettersen JA et al., “Vitamin D and executive functioning: are higher levels better?” Journal of Clinical and Experimental Neuropsychology, vol. 38, no. 4 (2016): 467–477 
  16. Miller JW et al., “Vitamin D status and rates of cognitive decline in a multiethnic cohort of older adults,” JAMA Neurology, vol. 72, no. 11 (November 2015): 1295–1303
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