Targeted Natural Interventions
The natural interventions outlined in this protocol are limited to those supported by evidence for memory modulation. Since overall brain health can significantly impact the acquisition, consolidation, and recall of memories, readers are encouraged to review the Age-Related Cognitive Decline protocol for additional suggestions.
Choline and Phosphatidylserine
Choline and phosphatidylserine are lipid components that support the structure and function of neurons involved in memory acquisition and recall. Choline plays an important role in the neuronal processes underlying memory via two different mechanisms. First, choline serves as a precursor for the neurotransmitter acetylcholine, which is important for neuronal signaling involved in memory (Poly 2011). Consequently, drugs that increase acetylcholine levels are an important part of treatment for Alzheimer’s disease. Second, the neurons in the brain have high levels of phosphatidylcholine, a lipid found in cell membranes. It is thought that diminished levels of phosphatidylcholine in neurons may contribute to memory loss and other forms of cognitive decline (Kullenberg 2012).
In animal models of memory loss, choline supplementation relieved memory impairment by improving the process of memory consolidation (Blake 2012). Trials in humans have also yielded promising results. Supplementation with alpha-glycerylphosphorylcholine (also known as alpha-GPC), a form of choline, has been found to improve memory and concentration. In young, healthy individuals, alpha-GPC has been shown to prevent drug-induced amnesia (Kidd 2005). Over 23 clinical trials on alpha-GPC have been performed. Some of the benefits observed include improved attention, memory, concentration, and cognition (Brady 2011). This compound has also been found to reduce memory loss and other signs of neurological damage due to stroke (Parnetti 2001; Barbagallo 1994). Another study found that individuals with higher choline intake performed better on memory tests, such as those that measured visual and verbal memory, and other measures of cognitive function (Poly 2011).
Phosphatidylserine, another lipid important for neuron health, is one of the most extensively studied compounds for memory impairment (Kullenberg 2012). Animal studies have found that phosphatidylserine lessened drug-induced amnesia (Vaisman 2009; Claro 2006). In addition, multiple studies show that supplementation with phosphatidylserine, either on its own or complexed with other fats, improves memory in elderly individuals with memory problems (Richter 2010; Kato-Kataoka 2010; Vakhapova 2010). Specifically, phosphatidylserine improves verbal recall of information and may improve cognitive deficits in elderly individuals with memory complaints but without signs of dementia (Richter 2010; Vakhapova 2010). Phosphatidylserine may also improve memory in people with attention deficit hyperactive disorder (Hirayama 2013). In addition to preserving neuron health, phosphatidylserine may be able to improve memory by increasing the levels of both glucose (aiding in the energy consumption of neurons) and acetylcholine in the brain (Kullenberg 2012). Another clinical study found that phosphatidylserine may enhance the effects of Ginkgo biloba, a plant well known for its benefits on brain health (Kennedy 2007).
Life Extension Study: Nutrient Complex May Positively Impact Cognitive Performance
A 2012 study conducted by Life Extension Clinical Research, Inc. assessed the impact of daily dosing of a dietary supplement containing alpha-glycerylphosphorylcholine (alpha-GPC), phosphatidylserine, vinpocetine, grape seed extract, wild blueberry extract, ashwagandha extract, and uridine-5’-monophosphate on cognitive performance in forty middle-aged to elderly subjects with subjective memory complaints.
An online cognitive assessment tool (Computerized Neuropsychological Test) was used to assess the change in cognitive performance from baseline to day 30 and day 60; the Global Impression Improvement (CGI-I) scale provided an overall clinically determined summary measure.
Twenty-nine subjects completed the study with no significant adverse events being reported. This study found a statistically significant improvement in three tests: working memory, inspection time, and executive function. Based on the CGI-I scale, improvement was noted after 30 and 60 days of product dosing.
The study was presented at the Experimental Biology 2012 multidisciplinary scientific conference in San Diego, California April 21-25, 2012.
B vitamins, including folate, thiamine, pyridoxine (vitamin B6), and vitamin B12, may also have an important role in preventing amnesia. Vitamin B12’s role in maintaining the health of the nervous system is particularly well established, since a lack of vitamin B12 may cause damage to the peripheral nervous system (Tangney 2012). Along with vitamin B12, the importance of folate and vitamin B6 for cognitive function has also come into focus. All of these vitamins are needed to reduce the levels of homocysteine in the brain; homocysteine contributes to vascular dysfunction (Morris 2005; Parletta 2013). Homocysteine levels tend to rise as people age and are associated with an increased risk of Alzheimer’s disease (Seshadri 2002; Tangney 2012).
In addition to its role as a risk factor for stroke, homocysteine is directly toxic to neurons, both in people with Alzheimer’s disease and in healthy individuals. One of the ways in which B vitamins may help prevent amnesia and other forms of cognitive decline is by lowering the levels of homocysteine. They may also help in the synthesis of different neurotransmitters needed for the brain to function properly (Parletta 2013). Low levels of several vitamin B12-related markers are also associated with low brain volume and decreased cognitive function (Tangney 2011; Tangney 2012). A study reported that supplementation with folate, vitamin B12, and vitamin B6 for 2 years slows cognitive decline and improves the clinical status (de Jager 2011), while other studies reported that they can also slow brain atrophy (Tangney 2012; Smith 2010). Ensuring adequate intake of thiamine is an important consideration in the prevention of amnesia, since lack of thiamine can cause Korsakoff’s syndrome, a symptom of which is amnesia (PubMed Health 2013).
The death of neurons within the hippocampus and other regions of the brain is thought to play a role in the development of amnesia. Acetyl-L-carnitine is a substance naturally produced by the body that may have a variety of neuroprotective effects. One of its main roles is to help the mitochondria, colloquially referred to as “cellular powerhouses,” produce energy more efficiently (Goo 2012; Malaguarnera 2011; Barwhal 2009). Moreover, it may help increase the levels of acetylcholine within the brain (Imperato 1989; White 1990; Jiang 2011; Schaevitz 2012). Supplementation with acetyl-L-carnitine has improved neurodegenerative dysfunction in many different animal models, including Alzheimer’s disease (Jiang 2011; Zhou 2011), age-related learning and memory impairment (Kobayashi 2010), poor blood flow/stroke (Barwhal 2009; Goo 2012; Zhang R 2012), and head trauma (Scafidi 2010). Acetyl-L-carnitine also improved cognitive function, including memory, in people with hepatic encephalopathy, a disease caused by liver damage (Malaguarnera 2011).
Coenzyme Q10 and Pyrroloquinoline quinone
Coenzyme Q10 (CoQ10), a naturally occurring vitamin-like substance involved in the cellular production of energy, may have some neuroprotective properties (Massaad 2011; Ishrat 2006). A related compound, pyrroloquinoline quinone (PQQ), may have neuroprotective effects as well (Zhang 2002; Ohwada 2008; Scanlon 1997). Studies of neuron cell cultures and animal models of amnesia have found that both of these substances may improve cognitive function and prevent cell death leading to amnesia (Hassanshahi 2012; Zhang 2002; Hassanshahi 2013; Massaad 2011; Ishrat 2006; Scanlon 1997; Zhang L 2012; Ohwada 2008). One potential cause of amnesia is stroke, which damages the hippocampus and other parts of the brain by depriving them of oxygen (a form of damage known as ischemia). CoQ10 protects the hippocampus and other parts of the brain from ischemic damage, suggesting that it could help prevent amnesia due to stroke (Hassanshahi 2012; Hassanshahi 2013). In animal models, CoQ10 and PQQ have reduced the behavioral effects of amnesia due to traumatic brain injury and amnesia-inducing medications (Zhang L 2012; Ohwada 2008; Ishrat 2006).
Omega-3 Fatty Acids
Omega-3 fatty acids are a class of fats that include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). In an animal model, these fats were shown to reverse ischemia-induced amnesia, and the improvement was maintained even after treatment was stopped (Fernandes 2008). Increasing intake of these fats, either by eating foods rich in omega-3 fatty acids (such as fatty fish) or taking fish oil supplements, may help protect the brain from amnesia. Studies on animal models of amnesia suggest that long-term treatment with omega-3 fatty acids can protect the brain from amnesia caused by low oxygen levels, medications, and lead poisoning (Fernandes 2008; Ajami 2012; Yadav 2012; Sharma 2012). Moreover, in humans, EPA and DHA supplementation has been shown to improve working memory (Narendran 2012).
Magnesium levels are higher in the fluid surrounding the brain and spine, called cerebrospinal fluid, than in the blood. This suggests magnesium plays an important role in the central nervous system (Slutsky 2010). In an animal model, a diet deficient in magnesium increased memory deficits after brain injury, and the administration of magnesium following acute brain injury significantly reduced tissue damage and improved behavioral outcome. In addition, a study showed that animals undergoing traumatic brain injury and receiving a diet with less magnesium had a higher mortality and worse neurological outcome (Hoane 2008). Evidence also suggests that people with mild-to-moderate Alzheimer’s disease often have diminished magnesium concentrations in their blood (Barbagallo 2011).
Magnesium supplementation also improves memory and reduces memory loss in many animal models of amnesia, suggesting that it could be an effective therapy for treating or preventing memory loss (Liu 2012; Slutsky 2010; Sarreshtehdari 2012; Uysal 2013). Although it is difficult for regular magnesium supplements to gain access to the brain, scientists have developed a modified form of magnesium, called magnesium-L-threonate, which is better able to get into the brain and may be more efficacious (Slutsky 2010).
Ginkgo biloba is one of the most extensively researched medicinal plants. It contains two different types of compounds, called flavone glycosides and terpene lactones, which have a variety of health benefits (Blecharz-Klin 2009). Importantly, ginkgo biloba may be able to improve brain health in a variety of ways: by improving energy utilization, preventing neuron death, and modulating neurotransmission (Blecharz-Klin 2009; Tobinaga 2012; Walesiuk 2009; Abdel-Wahab 2012). Trials on humans have yielded promising results: this plant improved memory in healthy middle-aged volunteers and slowed cognitive decline in the elderly (Amieva 2013; Kaschel 2011; Wesnes 2000). Another study reported that ginkgo biloba caused, after 14 days of administration, specific brain activity changes that resulted in improved working memory (Silberstein 2011).
Ashwagandha, also known as Indian ginseng, has been used in Ayurvedic medicine for centuries (Sandhu 2010). Studies suggest it may promote the growth, repair, and regeneration of damaged neurons, especially those that were damaged by Alzheimer’s and Parkinson’s disease and other neurodegenerative conditions (Singh 2011; Konar 2011).
Huperzine A is a compound derived from the Chinese plant Huperzia serrata. Its role in treating amnesia mainly stems from its ability to reversibly and selectively inhibit acetylcholinesterase. Inhibition of acetylcholinesterase leads to elevation of the neurotransmitter acetylcholine, which is important for memory; some Alzheimer’s disease medications also work by this mechanism (Ye 1999; Malkova 2011; Rafii 2011). In several animal models, huperzine A improved memory and cognitive function (Wang 2010; Shi 2012). It was also shown that, after oral administration for 8-24 weeks, 300-500 mcg of huperzine A daily improved the mental state of Alzheimer’s disease patients and was well tolerated (Wang 2009). It may also benefit people with cognitive deficiencies due to vascular disease (Xu 2012). In addition, huperzine A was shown in animal models to promote the growth of neurons within the hippocampus (Ma 2013).
Vinpocetine, a derivative of the periwinkle plant, may be useful in treating amnesia due to underlying neurological problems. In addition to having neuroprotective effects, vinpocetine may be able to enhance memory by improving the function of neurons in the hippocampus and other parts of the brain that control memory (Deshmukh 2009; Ratra 2011). Animal and cell culture studies have shown that vinpocetine can improve memory and protect neurons from a variety of different types of damage (Deshmukh 2009; Ratra 2011; Solanki 2011; Nyakas 2009; Groó 1987).