By Craig Weatherby

The brains of people with Alzheimer's disease feature a “plaque” composed of amyloid-beta protein. 

It remains unclear whether buildup of amyloid plaque is a cause or effect of Alzheimer's disease … but there's no doubt that it's toxic to brain cells. 

Now, a study from the UCLA School of Medicine suggests that vitamin D3 and omega-3s may enhance the body's ability to remove amyloid plaque from the brain. 

The scientists found that genes and “signaling networks” regulated by vitamin D3 and the omega-3 fatty acid DHA may help control inflammation and improve plaque clearance. 

Last year, the UCLA team gained lab evidence affirming the idea that vitamin D3 helps the immune system clear amyloid-beta protein, and clarifying how it works to do that (Mizwicki MT et al. 2012). 

Four years ago, a brain cell study from the same team indicated that curcumin and vitamin D3 – both shown to help clear amyloid plaque from the brain – do that even better together than separately (Masoumi A et al. 2009). 

The new study extends the previous vitamin D3 findings and highlights the role of omega-3 DHA ... one of the two major omega-3 fatty acids essential to human survival and health.

The other essential omega-3 is EPA ... but DHA and EPA are found together only in seafood and in fish or other marine oils.

“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 lead author Milan Fiala (UCLA 2013). 

Human study finds anti-Alzheimer's potential in omega-3 DHA and vitamin D3 
The UCLA study focused on critical immune-system cells called macrophages, which gobble up amyloid-beta and other waste products in the brain and body (Mizwicki MT et al. 2013). 

Scientists drew blood samples from Alzheimer's patients and healthy controls, isolated macrophages, and then incubated the immune cells overnight with amyloid-beta. 

They then added either vitamin D3 or a breakdown product of omega-3 DHA called resolvin D1 to some of the cells, in order to gauge the effect (if any) they'd exert on inflammation and amyloid-beta clearance. 

(To learn more about omega-3s and their novel, substantial inflammation-moderating effects, see “Fish Oil Linked to Lower Inflammation”, “Omega-3s May Help Deter (and Cure) Gum Disease”, and “Omega-3 Findings Point to Greater Cardiovascular Potential”.) 

Both vitamin D3 and DHA-derived resolvin D1 displayed two benefits: 
  • Curbed the brain-cell death caused by amyloid-beta. 
  • Raised the ability of Alzheimer's patients' macrophages to absorb amyloid-beta. 
Each nutrient elicited these effects through distinct cell-surface receptors as well as through cell-signaling pathways affected by vitamin D3 and resolvin D1 alike. 

Importantly, the macrophages in the Alzheimer's patients tended to expressed pro-inflammatory genes more than the healthy controls. 

And previous work by the UCLA team showed that there are two genetically distinct groups of Alzheimer's patients, whose macrophages show different characteristics. 

These differences have to do with the process called transcription, which is the first step leading to expression (activation) of specific genes. 

In fact, many of the health benefits of plant foods and fish exert stem from the influence of antioxidants and other factors on the expression (or suppression) of various genes. 

The UCLA team also found distinct transcription patterns in the two groups: 
  • Group 1 showed increased transcription of pro-inflammatory genes. 
  • Group 2 showed decreased transcription of pro-inflammatory genes. 
Encouragingly, vitamin D3 and resolvin D1 greatly improved the clearance of amyloid-beta by macrophages in cells taken from patients in both groups

However, the UCLA team discovered subtle differences in the effects the two substances had on the expression of inflammatory genes in the two groups: 
  •  In Group 1 – the increased-inflammation group – their macrophages showed decreased activation of pre-inflammatory genes. 
  • In Group 2 – the reduced-inflammation group – their macrophages showed increased expression of inflammatory genes (IL1 and TLRs) when either vitamin D3 or resolvin D1 were added. 
Dr. Fiala said that these differences might be associated with patients' intake or metabolism of vitamin D3 and DHA … as well with their intake of the other major fish-derived omega-3 fatty acid, called EPA. 

“We may find that we need to carefully balance supplementation with vitamin D3 and omega-3 fatty acids, depending on each patient, in order to help promote efficient clearing of amyloid-beta,” said Fiala. “This is a first step in understanding what form and in which patients these nutrition substances might work best.” (UCLA 2013) 

The UCLA team plans a larger study to help confirm the findings, as well as a clinical trial with omega-3 DHA. 

  • Mizwicki MT et al. 1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients. Journal of Alzheimer's Disease. Volume 34, Number 1 / 2013. DOI: 10.3233/JAD-121735. Accessed at 
  • Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, Mahanian M, Weitzman R, Hayden EY, Rosenthal MJ, Nemere I, Ringman J, Teplow DB. 1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients. J Alzheimers Dis. 2013 Jan 1;34(1):155-70. doi: 10.3233/JAD-121735. 
  • Mizwicki MT, Menegaz D, Zhang J, Barrientos-Durán A, Tse S, Cashman JR, Griffin PR, Fiala M. Genomic and nongenomic signaling induced by 1α,25(OH)2-vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer's disease macrophages. J Alzheimers Dis. 2012;29(1):51-62. doi: 10.3233/JAD-2012-110560. 
  • UCLA. Vitamin D, omega-3 may help clear plaques found in Alzheimer's. February 12, 2013. Accessed at 
  • Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K, Zheng X, Espinosa-Jeffrey A, Mahanian M, Liu PT, Hewison M, Mizwickie M, Cashman J, Fiala M. 1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer's disease patients. J Alzheimers Dis. 2009;17(3):703-17. doi: 10.3233/JAD-2009-1080.