Vitamin D

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Vitamin D, curcumin may help clear amyloid plaques found in Alzheimer's
UCLA Newsroom
Early research findings may lead to new treatments for the disease
By Rachel Champeau July 15, 2009 Category: Health Sciences, Research

UCLA scientists and colleagues from UC Riverside and the Human BioMolecular Research Institute have found that a form of vitamin D, together with a chemical found in turmeric spice called curcumin, may help stimulate the immune system to clear the brain of amyloid beta, which forms the plaques considered the hallmark of Alzheimer's disease.

The early research findings, which appear in the July issue of the Journal of Alzheimer's Disease, may lead to new approaches in preventing and treating Alzheimer's by utilizing the property of vitamin D3 — a form of vitamin D — both alone and together with natural or synthetic curcumin to boost the immune system in protecting the brain against amyloid beta...
http://newsroom.ucla.edu/portal/ucla/ucla-study-finds-vitamin-d-may-94903.aspx

Higher vitamin D linked to better physical functioning in elderly

by Neha Jindal - April 27, 2010

In a notable study, researchers claim to have found that higher blood levels of vitamin D improve physical functioning in the elderly.

Researchers at Wake Forest University in Winston-Salem, U.S., established that high levels of vitamin D not only help battle cold, cancer, diabetes and heart diseases but also perk up physical activity in the aged.

Lead researcher and assistant professor, internal medicine, Wake Forest University, Denise Houston, PhD, RD, was quoted by WebMD as saying, “Those with better vitamin D levels started out better and ended up better on physical performance tests.”
http://www.themedguru.com/20100427/newsfeature/higher-vitamin-d-linked-better-physical-functioning-elderly-86134554.html

Low Vitamin D Level Tied to Cognitive Decline

Study Shows Elderly People With Higher Vitamin D Levels Performed Better on Mental Tests

By Charlene Laino
WebMD Health News
Reviewed by Louise Chang, MD

April 16, 2010 (Toronto) -- Two new studies add to evidence that older people with low levels of vitamin D may be more likely to suffer from cognitive impairment.

The hope is that vitamin D supplements may be able to slow mental decline -- an intervention that one research team plans to put to the test this summer.

Vitamin D is best known for helping the body absorb calcium, which restores and strengthens bone, protecting against fracture.

But vitamin D also seems to have anti-inflammatory effects that may help keep blood vessels healthy, ensuring nutrient- and oxygen-rich blood flow to brain cells, says Amie Peterson, MD, of Oregon Health & Science University in Portland.

In addition, the presence of vitamin D receptors throughout the brain suggests that it may directly affect brain tissue, she tells WebMD.
http://www.webmd.com/healthy-aging/news/20100416/low-vitamin-d-level-tied-to-cognitive-decline

Do Vitamin D Deficiency and Cognitive Decline Go Hand‐in‐Hand?

Neurology Today
7 January 2010; Volume 10(1); p 10
FALLIK, DAWN

Two independent research groups showed a connection between vitamin D deficiency and cognitive decline in cross-sectional studies, while the third found no statistically significant association in a longitudinal study.

While vitamin D has long been known to assist calcium absorption in the body, investigators have begun to explore, as well, its role in supporting cognitive function and preventing dementia.

But exactly what that role is requires further research, according to the lead investigators of three studies published online Nov. 25 ahead of the Jan. 5 print edition of Neurology. Two independent research groups showed a connection between vitamin D deficiency and cognitive decline in cross-sectional studies, while the third found no statistically significant association in a longitudinal study.

Although the findings were inconclusive, the investigators agreed on this point: Clinicians need to be careful in prescribing supplements, because it is unclear what dose, if any, is most effective. And they warned patients not to consider vitamin D a “wonder drug,” because, unlike vitamin C excess, which the body eliminates, vitamin D is stored in fat, and an overdose can cause problems...
http://www.aan.com/elibrary/neurologytoday/?event=home.showArticle&id=ovid.com:/bib/ovftdb/00132985-201001070-00007

1α,25-dihydroxyvitamin D_{3} Interacts with Curcuminoids to Stimulate Amyloid-β Clearance by Macrophages of Alzheimer's Disease Patients
Journal of Alzheimer's Disease
Publisher IOS Press
ISSN 1387-2877 (Print) 1875-8908 (Online)
Issue Volume 17, Number 3 / 2009
DOI 10.3233/JAD-2009-1080
Pages 703-717

Authors
Ava Masoumi1, Ben Goldenson1, Senait Ghirmai2, Hripsime Avagyan1, Justin Zaghi1, Ken Abel2, Xueying Zheng2, Araceli Espinosa-Jeffrey3, Michelle Mahanian1, Phillip T. Liu4, Martin Hewison1, Matthew Mizwicki5, John Cashman2, Milan Fiala1

Abstract

Patients with Alzheimer's disease (AD) suffer from brain amyloidosis related to defective clearance of amyloid-β (Aβ) by the innate immune system. To improve the innate immune system of AD patients, we studied immune stimulation of macrophages by 1α,25(OH)_{2}-vitamin D_{3}(1,25D3) in combination with curcuminoids. AD patients' macrophages segregate into Type I (positively stimulated by curcuminoids regarding MGAT-III transcription) and Type II (not stimulated). In both Type I and Type II macrophages, 1,25D3 strongly stimulated Aβ phagocytosis and clearance while protecting against apoptosis. Certain synthetic curcuminoids in combination with 1,25D3 had additive effects on phagocytosis in Type I but not Type II macrophages. In addition, we investigated the mechanisms of 1,25D3 and curcuminoids in macrophages. The 1,25D3 genomic antagonist analog MK inhibited 1,25D3 but not curcuminoid effects, suggesting that 1,25D3 acts through the genomic pathway. In silico, 1,25D3 showed preferential binding to the genomic pocket of the vitamin D receptor, whereas bisdemethoxycurcumin showed preference for the non-genomic pocket. 1,25D3 is a promising hormone for AD immunoprophylaxis because in Type I macrophages combined treatment with 1,25D3 and curcuminoids has additive effects, and in Type II macrophages 1,25D3 treatment is effective alone. Human macrophages are a new paradigm for testing immune therapies for AD.
http://iospress.metapress.com/content/k457101686r62685/?p=299e6f877b2848309f40294ee2a89c52&pi=20

Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent.
Pascale CL, Miller MC, Chiu C, Boylan M, Caralopoulos IN, Gonzalez L, Johanson CE, Silverberg GD.
Fluids Barriers CNS. 2011 Jul 8;8(1):21.
Abstract

ABSTRACT: BACKGROUND: Age is the major risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD). There is an accumulation of amyloid-beta peptides (Abeta) in both the AD brain and the normal aging brain. Clearance of Abeta from the brain occurs via active transport at the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). With increasing age, the expression of the Abeta efflux transporters is decreased and the Abeta influx transporter expression is increased at the BBB, adding to the amyloid burden in the brain. Expression of the Abeta transporters at the choroid plexus (CP) epithelium as a function of aging was the subject of this study. Methods: This project investigated the changes in expression of the Abeta transporters, the low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (P-gp), LRP-2 (megalin) and the receptor for advanced glycation end-products (RAGE) at the BCSFB in Brown-Norway/Fischer rats at ages 3, 6, 9, 12, 20, 30 and 36 months, using real time RT-PCR to measure transporter mRNA expression, and immunohistochemistry (IHC) to measure transporter protein on isolated rat CP. For both the RT-PCR and the IHC analyses a single-factor ANOVA followed by Tukey's pairwise comparisons were used to analyze the data. Results: There was an increase in the transcription of the Abeta efflux transporters, LRP-1 and P-gp, no change in RAGE expression and a decrease in LRP-2, the CP epithelium influx transporter, at the BCSFB with aging. Decreased Abeta42 concentration in the CP, as measured by quantitative IHC, was associated with these Abeta transporter alterations. Conclusions: Age-dependent alterations in the CP Abeta transporters are associated with a decrease in Abeta42 accumulation in the CP, and are reciprocal to the changes seen in these transporters at the BBB, suggesting a possible compensatory role for the BCSFB in Abeta clearance in aging.

PMID:21740544 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21740544
Free Full Text: http://www.fluidsbarrierscns.com/content/8/1/21/abstract

Dietary vitamin D intake and sun exposure linked to lower risk of Alzheimer’s in France

Posted on April 23, 2012 by Dr. William Grant

A paper published ahead of print on April 13 found that consumption of vitamin D-rich foods and midday sun exposure were associated with significantly reduced risk of developing Alzheimer’s disease [Annweiler et al., 2012]. The study was an add-on to the Epidemiology of Osteoporosis (EPIDOS) Toulouse cohort study at 43.6º N.

Higher vitamin D dietary intake is associated with lower risk of Alzheimer’s disease: A 7-year follow-up.
Annweiler C, et al.
J Gerontol A Biol Sci Med Sci. 2012 Apr 13.

This cohort included women over the age of 75 years at time of enrollment and was designed to study risk factors for hip fractures over a four-year period. Women who had taken vitamin D supplements in the 18 months prior to enrollment were excluded. Dietary factors and midday sun exposure habits were examined at time of enrollment. The mean dietary vitamin D intake was 334±172 IU/day. The presence of Alzheimer’s disease and other dementias was assessed seven years after enrollment.

Those in the highest fifth of vitamin D intake had one-quarter the incidence rate of Alzheimer’s disease as the other four fifths [odds ratio (OR) = 0.23 (95% confidence interval (CI), 0.08-0.69)]. In addition, those in the highest fifth of sun exposure had half the incidence rate of Alzheimer’s disease [OR = 0.45 (95% CI, 0.24-0.85)]. Neither dietary vitamin D intake nor sun exposure was significantly associated with risk of other dementia.

As mentioned in the paper, there is a considerable body of literature reporting that fish consumption is associated with reduced risk of Alzheimer’s disease, with the usual reason given that fish is an important dietary source of omega-3 fatty acids. This finding was likely first reported in an ecological study in 1997 [Grant, 1997]. Thus, it is not clear from the present study how much of the reduced risk of Alzheimer’s disease was due to omega-3 fatty acids and how much to vitamin D.

However, the finding regarding sun exposure at midday strongly supports the role of vitamin D in reducing risk. Casual sun exposure in England for those aged 45 years is sufficient to increase serum 25-hydroxyvitamin D concentrations by 38 nmol/l (15 ng/ml) [Hyppönen and Power, 2007]. This increase is equivalent to about 1500-2000 IU/day [Garland, 2011]. However, for those over the age of 75 years, vitamin D production rates would be less, perhaps one-half as much [MacLaughlin and Holick, 1985].

Thus, this study provides good evidence that fish consumption and midday sun exposure reduce the risk of Alzheimer’s disease, with vitamin D being the likely agent. The neuroprotective actions of vitamin D are discussed in the paper by Annweiler et al.

References

Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Herrmann FR, Beauchet O. Higher vitamin D dietary intake is associated with lower risk of Alzheimer’s disease: A 7-year follow-up. J Gerontol A Biol Sci Med Sci. 2012 Apr 13. [Epub ahead of print]

Garland CF, French CB, Baggerly LL, Heaney RP. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res 2011:31: 617-22.

Grant WB. Dietary links to Alzheimer’s disease. Alz Dis Rev 1997;2:42-55. (http://www.sunarc.org/JAD97.pdf)

Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007 Mar;85(3):860-8.

MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985 Oct;76(4):1536-8.

PMID: 22503994 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/22503994
http://blog.vitamindcouncil.org/2012/04/23/dietary-vitamin-d-intake-and-sun-exposure-linked-to-lower-risk-of-alzheimers-in-france/

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