Health Professional – Cognitive Function

Choline, an essential nutrient that is functionally complementary to B vitamins and omega-3 fatty acids, is critical to overall health and healthy cognitive function.

Choline is a critical component of the building blocks of the nervous system, including neurotransmitters that form the mechanistic basis for memory. Choline is part of the messaging system of the brain, and functions directly and indirectly in brain activities and cognitive development for the fetus and infant.

Specifically, choline is a precursor to the neurotransmitter acetylcholine. Choline also functions as part of phosphatidylcholine, a structural component of the phospholipid membrane of all cells, including glial and neuronal cells. Choline is a precursor to sphingomyelin, which is important to the integrity of neurons and in the metabolism of molecules, including diacylglycerol and ceramide, which function in intracellular signaling.

Choline supports the communication between neurons in the brain and promotes better availability of neurotransmitters for signaling within the brain. The availability of choline at different stages of human development and aging appears to be significant in improving the density and branching of dendrites, which results in more contact points for neurotransmission (McCann et al, 2006). It also supplies the raw materials for the enzyme that generates the neurotransmitter, acetylcholine. Choline availability affects the strength of neuronal response to stimulation in the parts of the brain responsible for memory, including the hippocampus (Glen et al, 2007; Jones et al, 1999; Li et al, 2004).

The level of choline in the brain is directly affected by its levels in plasma, which is supported through dietary intake and supplementation (Wurtman et al, 2009; Babb et al, 2004; Hirsch et al, 1978). Free choline reaches the brain by crossing the blood-brain barrier (Wurtman et al, 2009). Oral intake of choline affects both blood levels of choline and acetylcholine (Hirsch et al, 1978; Cohen and Wurtman, 1975; Cohen and Wurtman, 1976; Zeisel, 1981). In deficiency states, membrane phospholipids and sphingomyelin are broken down so that free choline can support brain functions and provide for its release to the hippocampus (Molinengo et al, 1997). Choline status can also up- or down-regulate the activity of enzymes that synthesize acetylcholine, the neurotransmitter (Cermak et al, 1998). Inadequate choline intake compromises neurotransmission, and/or nerve tissue and cellular integrity as the body works to maintain a supply of free choline to the brain.

Choline's Role in Promoting Development of Human Cognitive Function

Gestational choline supply has a significant influence on the structure and cholinergic functions of the fetal and infant nervous system. Choline availability to a fetus appears to have an enduring significance in that individual at an advanced age (Meck et al, 2008). Choline is needed before birth as a precursor for the structural phospholipids needed to construct the membranes of cholinergic neurons (Wurtman et al, 2009; Wurtman, 2008). This function is similar to the effects of the omega-3 fatty acid docasahexaenoic acid (DHA). Both choline and DHA promote the extent of dendrite branching in hippocampal neurons (Li et al, 2004; Wurtman, 2008), which supports synaptic communication for neurotransmitters. Choline and DHA metabolism is related to circulating levels of phosphatides and diacylglycerol, which function in messaging capacity of the cell.

Choline supplementation and deprivation studies have been conducted in cell culture and animal models (McCann et al, 2006; Pacelli et al, 2010; Meck et al, 2003; Meck et al, 1988; Meck et al, 1999; Williams et al, 1998) and have examined the nutrient's role in cell differentiation and migration in the hippocampus and cortex, regions of the brain that regulate learning and memory. The availability of prenatal choline corresponds to morphological change and increase in the overall size of cholinergic neurons in the basal forebrain (Li et al, 2004; Williams et al, 1998), which facilitates neurotransmission. The neurophysiological development of the hippocampus is directly affected by choline intake as well (Li et al, 2004; Albright et al, 1999). In the hippocampus, choline affects the level of nerve growth factor (Sandstrom et al, 2002), a factor that is important in the refinement of neural connections that enhance communication and improve learning and memory functions (Jones et al, 1999; Pyapali et al, 1998; Sandstrom et al, 2002). Synaptic connections continue to be formed in the hippocampus and basal forebrain in the months and years after birth (Jones et al, 1999; Li et al, 2004; Yen et al, 2001; Albright et al, 1999), so choline nutrition in infancy and childhood are critically important.

Benefits of pre- and post-natal choline availability are seen in behavioral studies in animal species (McCann et al, 2006). Performance enhancement in offspring provided sufficient choline early in life is most evident in better execution of complex memory-related tasks, particularly those involving visio-spatial and serial learning and memory (Li et al, 2004; Meck et al, 2003; Meck et al, 1999).

Choline's Role in Preventing Cognitive Decline in Aging

Cognitive decline in aging is due in part to oxidative events, including an increase in reactive oxygen species, spurring the oxidation of low density lipoproteins, DNA damage, the rampant growth of smooth muscle cells, and aggregation of platelets that result in occlusive damage to tissues and organs (Ulrey et al, 2005; Kang, 1996; Gilette-Guyonnet et al, 2007). Such oxidative events occur when high levels of homocysteine are present. Homocysteine is a metabolically-generated amino acid which is directly and inversely associated with choline intake (Cho et al, 2006; Olthof et al, 2005). Homocysteine may be a biomarker, by-product, risk factor, or active agent of biochemical change (Hustad et al, 2007); however, it is widely thought to have a role in cognitive decline in normal aging, and may atrophy parts of the brain hippocampus and cortex (Garcia and Zanibbi, 2004).

It is estimated that 5-10% of the general U.S. population has elevated homocysteine (homocysteinemia), with three-fold greater incidence in people above age 65 (Lokk, 2003; Gillette-Guyonnet et al, 2007). Its relationship in cognitive decline is most apparent in older individuals. Cognitive performance testing in humans showed diminished abilities in individuals with elevated homocysteine, including compromised abstract reasoning, delayed recall in verbal and visual memory, executive performance, visual organization, object naming, concentration, and language (Elias et al, 2005). Research is ongoing to further define the relationship between dietary choline, homocysteine, and cognitive decline in aging.

Failure in cognitive functions that occur in aging include reduced synthesis of the neurotransmitter acetylcholine, breakdown or insufficient repair of neurons, loss of myelin and dendrite branches, and cell death in the hippocampus (Berry and Lockwood, 2004). If one or more of these factors affecting memory loss may be modulated by choline intake, then choline intake in normal aging may restore cognitive function in the otherwise healthy aging individual.

Importance of Cognitive Function to Consumers

Maintaining mental sharpness, including memory, as we age is the number one consumer concern in the U.S. and abroad; lack of mental sharpness is also among the top 10 consumer health concerns.

Sales of brain health supplements reached $660 million in 2013, up 5.4% vs 2012.


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