Why Have the Benefits of DHA Not Been Borne Out in the Treatment and Prevention of Alzheimer's Disease? A Narrative Review Focused on DHA Metabolism and Adipose Tissue.

Rory J Heath,Thomas R Wood

doi:10.3390/ijms222111826

Abstract

Docosahexaenoic acid (DHA), an omega-3 fatty acid rich in seafood, is linked to Alzheimer’s Disease via strong epidemiological and pre-clinical evidence, yet fish oil or other DHA supplementation has not consistently shown benefit to the prevention or treatment of Alzheimer’s Disease. Furthermore, autopsy studies of Alzheimer’s Disease brain show variable DHA status, demonstrating that the relationship between DHA and neurodegeneration is complex and not fully understood. Recently, it has been suggested that the forms of DHA in the diet and plasma have specific metabolic fates that may affect brain uptake; however, the effect of DHA form on brain uptake is less pronounced in studies of longer duration. One major confounder of studies relating dietary DHA and Alzheimer’s Disease may be that adipose tissue acts as a long-term depot of DHA for the brain, but this is poorly understood in the context of neurodegeneration. Future work is required to develop biomarkers of brain DHA and better understand DHA-based therapies in the setting of altered brain DHA uptake to help determine whether brain DHA should remain an important target in the prevention of Alzheimer’s Disease.

Highlights

Alzheimer’s Disease (AD) is the most common cause of dementia [1]
PL- and Docosahexaenoic acid (DHA) esterified to triglyceride (TG-DHA) as krill oil, krill meal or fish oil with regard to incorporation into plasma phospholipids [144,145]. These results show that, while the PL form provides rapid elevation of plasma and brain DHA shortly after administration, passing time allows the effects of dietary TG-DHA to equalize and even surpass PL-DHA to be the major supplier of tissue and brain DHA
This paper has aimed to expand discussion surrounding the utilization of the metabolic fates of dietary and plasma forms of DHA to target tissue and brain uptake in both normal and diseased physiology

Summary

Introduction

Alzheimer’s Disease (AD) is the most common cause of dementia [1]. Docosahexaenoic acid (DHA) is a N3 long-chain polyunsaturated fatty acid (LCPUFA). DHA synthesis from other N3 polyunsaturated fatty acid (PUFA) precursors occurs inefficiently in the liver, with some variation determined by genetic polymorphism [6,7,8], and optimal DHA levels are largely thought to require some dietary DHA [9,10,11]. DHA is essential for proper neurological development and functioning throughout the lifespan. The brain relies on DHA supplied via plasma, and deficiency impairs proper development of vision, cognitive functioning, and behavior [12,13,14,15,16]

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