Docosahexaenoic Acid: A Potential Modulator of Brain Tumors and

Although not specific to any particular region in the brain, primary tumors and/or metastases from other organs are life threatening and mortality is rapid. Treatment options for patients with primary brain tumors or metastases are limited and include (either alone or combined) whole-brain radiotherapy, cranial stereotactic radiosurgery, neurosurgery, and steroids [1,2]. However, the standard treatment for multiple brain lesions remains whole-brain radiation (WBRT) for symptom control. For cancer patients treated with WBRT, median survival is 3–6 months; in patients treated with steroids alone, 6–8 weeks; and for untreated patients with symptomatic brain metastasis, median survival is less than one month [3,4]. Furthermore, these treatments do not improve the quality of life and adversely affect cognitive functions. Clearly, patients who have brain tumors or are at risk of developing metastatic tumors need other treatment options. The human brain contains nearly 60% fat, mostly in the cellular membranes. The lipid composition of the cellular membrane varies among cells of different organs and tissues. The lipid composition within cells also varies among plasma membranes, endoplasmic reticulum, mitochondrial membranes, and nuclear membranes. The biophysical properties of a membrane are regulated by the relative amounts and types of fatty acids present within the membrane’s phospholipid bilayer. Since the membranes are home to nearly 1/3 of all cellular proteins, including enzymes, transport proteins, ion channels, receptors, adhesion proteins, and components of cellular signaling pathways, the composition of these cellular membranes is extremely critical for cell responsiveness under normal and pathological situations. In the brain, neuronal membranes contain phospholipids that are predominantly rich in docosahexaenoic acid (DHA), the most unsaturated of the long-chain omega-3 fatty acids [5-7]. DHA, particularly abundant in cold-water fatty fish, has been excellently reviewed in recent articles for its role in brain development and intelligence [8-12]. Some authors have suggested that early humans who lived near water sources and ate seafood experienced a significant change in their brains, acquiring learning capabilities and intelligence that has revolutionized life on planet earth [13,14]. In contrast, Australopithecines did not have access to omega-3 fatty acids and, for 3 million years, got stuck at a brain capacity that was not much bigger than a chimpanzee’s.