Saturday, November 15, 2014

Functional Food Product: Cocoa Mocha (Brain Health)

Product goal
Reverse cognitive decline from aging and improve cognitive performance.

Primary Ingredients
Caffeinated coffee – 2 cups
MCT oil – 30 g 
Flavanol-rich cocoa – 500 mg flavanols
Phosphatidylserine – 300 mg


My functional food product is a beverage marketed to improve cognition in aging individuals.  The goals of the formula are to reverse cognitive decline and improve mental performance.  As a large portion of the population is entering the elderly years of life, there is an emerging market for products that can increase cognition.  Consumers particularly in the United States are becoming more aware of the potential benefits of therapeutic foods and supplements, and this is increasing demand for such products.  Beverages have historically been the most popular choice for function foods, particularly those targeting energy and mood enhancement.  

The cognitive-enhancing beverage proposed here contains several ingredients with considerable research showing their potential benefits.  Much of the research suggests that the ingredients may benefit people with specific neurodegenerative diseases, but the scope of this product is not solely on these populations.  Mild cognitive decline is more prevalent in the aging population than is dementia, Alzheimer’s disease, or Parkinson’s disease.  There is a large market for products that can enhance cognition in aging individuals, and Cocoa Mocha fits this niche perfectly.

The base of Cocoa Mocha is caffeinated coffee, America’s favorite morning beverage.  This will be supplemented with high-flavanol cocoa, medium-chain triglycerides (MCT), phosphatidylserine, lecithin (emulsifier), and stevia (sweetneer).  The beverage is to be consumed in the morning several hours before the first meal of the day.  The rationale is that the protein and carbohydrate in other foods would reduce the product’s beneficial effects, particularly in the induction of mild ketosis and the increased expression of AMPK.  It still can be consumed with other dietary supplements such as fish oil.  The ingredients are blended into a rich, foamy and delicious morning beverage that will perk up your brain and body.

I have formulated my product with the assumption that individuals are not suffering from any nutrient deficiencies.  This is despite the high prevalence of sub-optimal levels of nutrients in today’s population.  Such nutrients include magnesium, taurine, carnitine, creatine, choline, fat-soluble vitamins, docosahexaenoic acid (DHA), and soluble fiber.  I would encourage that people ensure they are getting adequate amounts of these nutrients in their diets.  Other supplements that may benefit cognition during aging include astaxanthin, cholinergenic compounds like alpha-glycerylphosphorylcholine (GPC), acetylcholine, and citicoline, and nootropic drugs like piracetam, huperzine A, and vinpocetine.(Polich & Gloria, 2001)  Other dietary strategies that can improve brain function include polyphenol-rich foods like blueberries, spices and herbs, and emphasizing whole foods over processed and refined foods. (Kennedy & Scholey, 2006),(Dwivedi, Singh, Mohd, & Jawaid, 2012),(Solfrizzi, Panza, & Capurso, 2003)

Cognitive Decline

Aging is an inevitable consequence of life.  In humans, normal aging is accompanied by gradual degeneration as the body cannot maintain regenerative processes.  There are various theories of aging that attempt to find treatable causal factors, but we have yet to devise an effective strategy to stop the inevitable.  We expect physical deterioration to occur, but we usually consider neurodegeneration and cognitive decline as preventable diseases, even in aging individuals.  Minor cognitive decline can include memory loss, reduced attention span, slower mental processing, and reduced capacity of working memory, all of which can reduce an individual’s quality of life.  Advanced neurodegeneration can eventually lead to Alzheimer’s disease, Parkinson’s disease, and dementia, all of which severely affect cognitive abilities.

Advanced neurodegenerative diseases are a major concern in the aging population.  There is no definitive cause of these diseases, and there are no reliable cures.  Nevertheless, mild cognitive impairment often precedes advanced neurodegenerative diseases, and at this stage the progression of disease may be reversible.  In a 2008 study, it was estimated that 22.2% of Americans 71 years or older have cognitive impairment without dementia.(Plassman et al., 2008)  It is often more effective to take preventative measures against a disease than to treat it once it develops.  Therefore, I propose that we target the reversal of cognitive decline as a preventative measure against advanced cognitive impairment. 

Diet and lifestyle are primary factors in the development of disease.  A healthful diet has a tremendous effect on the development of numerous diseases partly through epigenetic influence.  Aging combines various degenerative processes, many of which are influenced by diet.  Given the increasing size of the elderly population, it is important that we pay greater attention to cognitive health, including mild cognitive impairment.  I believe that the development of a functional food can be effective in reversing mild cognitive impairment and that such a product would be welcomed in today’s marketplace.

Cognitive decline does not affect all individuals equally.  There are myriad genetic and environmental influences that can lead to a decline of cognitive abilities.  It is possible that there is no single causal factor, instead requiring a combination of factors.  Such factors may include oxidative stress, inflammation, hormone imbalance, nutrient deficiency, stressful lifestyle, social and emotional health, infection, and other medical conditions.(“Age Related Cognitive Decline,” n.d.)  Some factors require special attention, such as nutrient deficiency, genetics, and underlying medical conditions, while others are a result of lifestyle.  I will limit the focus of my food product to include only those factors that are particularly influenced by diet and can benefit a majority of the population.  

The aging brain is affected on many levels.  There is a deterioration of neuronal and mitochondrial membranes, leading to impaired metabolism and neuronal function.(“Age Related Cognitive Decline,” n.d.)  Neurotransmitter synthesis and signaling decline; synaptic density and plasticity are reduced, and myelinated axons shorten.  The various segments of the brain also shrink with age.  It is estimated that anatomical changes in the brain account for 25% to 100% of the difference in cognitive ability between young and aged people.(“Age Related Cognitive Decline,” n.d.)  This shows that physical deterioration correlates with loss in cognitive ability and suggests that preventative measures that preserve brain structure may preserve cognitive ability.

Memory and motor deficits are common symptoms of degenerating brains and appear similarly in both humans and animals.(Joseph, Shukitt-Hale, & Casadesus, 2005)  In animal models, cognitive function is usually measured using a maze, and motor function is usually measured using various tests.  Maze tests assess memory acquisition, working memory, and long-term memory.  Old rats are shown to have decrements in both long-term and working memory in maze tests.(Joseph et al., 2005)  Much of the clinical research related to cognitive impairment has been performed using animal models.   

MCT oil

Medium-chain triglycerides (MCTs) are unique dietary fats that have a variety of potential health benefits.  Typically, MCTs are triacylglycerols whose fatty acid chains are 8 and 10 carbons in length.  Because of their relatively short chain lengths, medium-chain fatty acids (MFCAs) have unique properties compared to long-chain fatty acids that give them certain dietary properties. 

Unlike conventional fats, which are absorbed and transported in the lymphatic system via chylomicrons, MCTs are absorbed into the portal vein and metabolized in the liver.  Long-chain triglycerides are transported in chylomicrons and are efficiently stored in adipose tissue.  Conversely, MCTs are metabolized in the liver, where they are readily burned for energy.  Those MCFAs that are not burned for energy can then be elongated through de novo lipogenesis.  Similar to carbohydrates, MCTs are a readily accessible fuel, but do not cause blood glucose spikes and are not dependent on insulin for metabolism.  

The efficient metabolism of MCTs is partly due to their entry into mitochondria without carnitine.  This results in high levels of acetyl-coA, which then can enter the citric acid cycle to produce NADH and FADH2 for energy, act as a substrate in de novo lipogenesis, or contribute to the production of ketone bodies for metabolism in other tissues.  Ketone bodies include β-hydroxybutyric acid, acetoacetic acid, and acetone.  They are efficiently metabolized by skeletal muscle, cardiac muscle, and most neurons.  Plasma ketone bodies are elevated in people that are fasting to supply the brain and nervous system with fuel while reducing the demand for glucose from gluconeogenesis.  

Therapeutic use of MCT oil to induce ketosis can benefit aging individuals who have compromised mitochondrial function.(Henderson, 2008)  Caloric restriction, fasting, and ketosis have been shown to increase mitochondrial autophagy, which recycles damaged mitochondria and replaces them with new mitochondria upon refeeding.(Kubli & Gustafsson, 2012)  Over time, this may reverse mitochondrial dysfunction and improve mitochondrial ATP production and neuronal function, improving cognition.

There is evidence that people with neurological degeneration may in fact be insulin resistant in the brain.(Bomfim et al., 2012)  This has led some people to refer to this state as “type 3 diabetes.”  When brain cells have insufficient energy production, they can die.  This damage may accumulate and lead to brain degeneration.  Glucose is the primary fuel source for brain cells.  When brain cells become resistant to insulin, glucose utilization is inhibited and energy production decreases.

Insulin enhances the uptake of glucose into cells by signaling GLUT4 expression.  Another function of insulin is to upregulate pyruvate dehydrogenase, which converts pyruvate from glycolysis to acetyl-coA.  This promotes glucose utilization and reduces the backlog of glucose in the cytosol and blood.  Another way insulin promotes glucose utilization is to decrease plasma non-esterified fatty acids (NEFAs).  In people with insulin resistance, glucose metabolism is compromised, yet blood glucose may still remain high.  The body compensates for the perceived low glucose by releasing NEFAs as a fuel source.  Fat metabolism itself inhibits glucose metabolism via the Randle cycle through inhibition of carnitine palmitoyltransferase 1.(Bevilacqua et al., 1990)  Additionally, simultaneous elevation of blood glucose and NEFAs can damage cells, further reducing metabolic function.(El-Assaad et al., 2003)  This presents somewhat of a positive feedback loop that is encouraged by a diet with excess carbohydrate and fat.

In people with insulin resistance, the utilization of glucose in compromised.  MCTs offer an alternative fuel source because they do not require pyruvate dehydrogenase to produce acetyl-coA or require carnitine for transport into mitochondria.  MCTs have been shown to increase key metabolic enzymes involved in the citric acid cycle.(Fushiki, Matsumoto, Inoue, Kawada, & Sugimoto, 1995)  Dietary ketosis has been shown to decrease insulin resistance in brain.(Park, Kim, & Daily, 2011)  MCT oil consumed without a significant carbohydrate or protein load, such as during an intermittent fasting period can resemble a state of fasting that may improve metabolic maintenance and repair.  This suggests strategic feeding of MCT oil may help to restore metabolic function by enhancing metabolic repair and contribute to efficient aerobic metabolism.  Such maintenance may lead to improved function of neurons and improve mental function and cognition.

Research supports this hypothesis showing improvement in cognitive function in both animals and humans.  Aged dogs fed MCT oil performed better on cognitive tests.(Pan et al., 2010)  Their brains also had reduced amounts of amyloid beta plaque precursors, which are believed to contribute to Alzheimer’s disease.(Studzinski et al., 2008) Humans consuming MCT oil also performed better on cognitive tests.  Type 1 diabetics performed better after consuming MCT oil than controls.(Liu, 2008) Alzheimer’s patients fed ketones showed significant improvements in cognitive performance on the AD Assessment Scale-Cognitive Subscale.(Henderson et al., 2009)  In a study of individuals with cognitive impairment, MCT oil-induced ketosis improved cognitive abilities in all subjects relative to control.(Reger et al., 2004)  MCT oil supplementation at 30g/d in healthy humans has been shown to be safely ketogenic without side effects.(Courchesne-Loyer et al., 2012)  In such cases, ketones are estimated to contribute up to 8 – 9 % of brain energy metabolism.


Phosphatidylserine (PS) is one of the five phospholipid required by human cells, another primary one being phosphatidylcholine.  Phospholipids contribute to the structure of cell membranes.  Phosphatidylserine particularly supports cell fusion, neurotransmitter release, and signal transduction.  This is important in the proper neuronal processing of environmental stimuli.  PS is essential to maintain memory function and neuroplasticity.  Phosphatidylcholine is also very important to neuronal function.  Supplementation with phosphatidylcholine precursors such as alpha-GPC or citicoline may offer benefits, but they are expensive and not suitable for the goals of this formulation.  Instead, lecithin is included to be an emulsifier and a rich source of phosphatidylcholine.

Studies suggest that PS can benefit people of all ages.  In middle-aged and elderly individuals, PS has been shown to prevent and restore memory loss and alleviate stress and anxiety.(Crook et al., 1991),(Baumeister, Barthel, Geiss, & Weiss, 2008; Hellhammer et al., 2004)  In a double-blind, placebo-controlled trial of 425 patients aged 65-93 with moderate-to-severe cognitive decline, six months of daily supplementation of 300 mg PS resulted in consistent improvement in memory, learning, and socialization.(Cenacchi, Bertoldin, Farina, Fiori, & Crepaldi, 1993)  In a recent clinical trial of children with ADHD, 200 mg daily supplementation improved attention, short-term auditory memory, and impulsivity.(Hirayama et al., 2013)  A summary of other clinical studies appears in Table 1.(Kidd, 1996)

Brain cell membrane phospholipids also contain DHA.  Historically, PS derived from bovine brain has been used in clinical trials, but recent studies of soy-derived PS has been shown to be similarly effective.(Blokland, Honig, Browns, & Jolles, 1999)  DHA has been repeatedly shown to improve cognition, reduce cognitive decline, and improve neurological disease.(Kotani et al., 2006),(Yurko-Mauro et al., 2010),(Johnson et al., 2008),(Quinn JF, 2010)  Consuming DHA along with PS and antioxidants may improve the effectiveness of supplementation.(Kidd, 2007)  

DHA has been a highly promoted supplement recently, and it is likely that individuals looking to increase cognitive function with a functional food would already be taking such a supplement.  Therefore, the inclusion of DHA in my formulation is not necessary.  Additionally, DHA is particularly susceptible to peroxidation, and a heated environment could accelerate this process, even in the presence of antioxidants.  It should be noted that lecithin is relatively high in linoleic acid, which is also susceptible to such degradation, but it is not as susceptible as the highly-unsaturated DHA.

Phosphatidylserine has been shown to be so effective against cognitive decline that the FDA has allowed the following two label claims: "Consumption of phosphatidylserine may reduce the risk of dementia in the elderly” and "Consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly.”

Oxidative Stress

One of the most important factors affecting age-related cognitive decline is oxidative stress.(Joseph et al., 2005)  The central nervous system is particularly vulnerable to oxidative stress, and this vulnerability increases with aging.  The central nervous system is also vulnerable to damage from inflammation, and elevated levels of inflammatory markers have been measured in aged animals and humans.  Inducing neuronal inflammation through administration of lipopolysaccharide has been shown to reproduce many of the negative changes seen in the brains of individuals with Alzheimer’s disease.(Joseph et al., 2005) lipopolysaccharide has been shown to reproduce many of the negative changes seen in the brains of individuals with Alzheimer’s disease.(Joseph et al., 2005)

Antioxidants are believed to confer protective effects against oxidative damage and inflammation in the brain during aging.(Cantuti-Castelvetri, Shukitt-Hale, & Joseph, 2000; Joseph et al., 2005)  Plants synthesize a variety of photochemicals including polyphenols, some of which having antioxidant and/or anti-inflammatory properties.  Dietary polyphenols have various functions in the body, one of which is antioxidant activity.  Additionally, polyphenols can have beneficial effects by interacting with nuclear receptors to modulate enzymes involved in cell signaling and antioxidant responses.(Virgili & Marino, 2008),(Williams, Spencer, & Rice-Evans, 2004)  In the elderly, a diet high in some flavonoid-rich foods has been associated with improved cognitive performance in a dose-dependent manner.(Nurk et al., 2009)


Coffee is one of the most popular beverages in the United States.  Coffee contains a variety of extractable compounds, one of which is caffeine.  Caffeine has numerous effects on the brain and nervous system and has been shown to improve mood, reaction time, memory, and general cognitive function.(Ruxton, 2008)  Caffeine blocks the inhibitory effects of adenosine and can increase neuronal firing in the brain by increasing the release of catecholamine neurotransmitters such as dopamine and norepinepherine.(Fredholm, 1995),(Nehlig, Daval, & Debry, 1992)  Caffeine increases our metabolism and promotes the mobilization of fatty acids from adipose tissue for oxidation as fuel.(Acheson, Zahorska-Markiewicz, Pittet, Anantharaman, & Jéquier, 1980),(Arciero, Gardner, Calles-Escandon, Benowitz, & Poehlman, 1995)  Caffeine also improves the integrity of the blood-brain barrier in animal models of Alzheimer’s and Parkinson’s diseases.(Chen, Ghribi, & Geiger, 2010)  

Coffee has been associated with decreased risk of Alzheimer’s disease, Parkinson’s disease, and dementia.(Quintana, Allam, Del Castillo, & Navajas, 2007),(Hu, Bidel, Jousilahti, Antikainen, & Tuomilehto, 2007),(Ross G, 2000),(Eskelinen, Ngandu, Tuomilehto, Soininen, & Kivipelto, 2009)  These benefits may go beyond simply its caffeine content.  Caffeinated coffee specifically has been associated with significantly slower cognitive decline compared to other caffeinated products.(Vercambre, Berr, Ritchie, & Kang, 2013)  There may also be a synergistic effect, as the beneficial effects of coffee in Alzheimer’s mice was better than caffeine or decaffeinated coffee alone.(Cao et al., 2011)  Aged rats that drank coffee performed better on working memory tasks than both control rats and those supplemented with caffeine alone.(Shukitt-Hale, Miller, Chu, Lyle, & Joseph, 2013)  

Coffee consumption has been inversely associated with cognitive decline in the elderly.(van Gelder et al., 2006)  In a study of 676 individuals with an average age of 75 years, coffee consumption over a 10-year period was associated with significantly lower cognitive decline.(van Gelder et al., 2006)  Three daily cups of coffee was associated with a 4.3 times lower decline in cognitive function compared with non-consumers.  This suggests that regular coffee consumption may be protective against cognitive decline in aging brains. 

Oxidative damage is a consequence of oxidative metabolism during aging.  This may result in decreased cognitive ability as damage accumulates in neurons.  Coffee is a rich source of polyphenols, one class of phytochemicals with antioxidant activity.  Coffee has been shown to reduce oxidative damage and improve general markers of health.(Bakuradze et al., 2011),(Mišík et al., 2010)  Coffee particularly contains chlorogenic acid, which is believed to be responsible for much of the neuroprotective effects of coffee.(Chu et al., 2009)  One study showed that enrichment of coffee with chlorogenic acid showed improvements in mood and cognition.(Cropley et al., 2012)  This emphasizes the synergistic effects of compounds within foods, and the collective effects of such combinations may be more beneficial than compounds in isolation, particularly in coffee. 


Chocolate is also a rich source of polyphenols.  Flavonoids, and particularly flavanols, are the polyphenols of interest in chocolate.  Flavanols have diverse physiologic effects, particularly with regards to vascular function.(Francis, Head, Morris, & Macdonald, 2006)  In one study, healthy individuals who consumed 150 mg of cocoa flavanols for 5 days showed increased brain signaling during cognitive tasks compared to controls.(Francis et al., 2006)  This was speculated to be a result of either altered neuronal activity or a change in vascular responsiveness.  In an evaluation of the relationship between cerebral blood flow and chocolate consumption, a single acute dose of flavanol-rich cocoa showed an increase in cerebral blood flow to gray matter.(Francis et al., 2006)  This suggests that cocoa consumption may provide vascular protection including that within the brain.

In a study of the effect of cocoa on cognitive function, elderly individuals with mild cognitive impairment consumed cocoa with various levels of flavanols for 8 weeks and then were tested for cognitive function.(Desideri et al., 2012)  The high-flavanol (990mg) and intermediate-flavanol (520mg) groups showed significantly improved cognitive scores, higher insulin sensitivity, and lower blood pressure and lipid peroxidation compared to the low-flavanol (45mg) group.  The per capita chocolate consumption of countries is also significantly (p < 0.0001) associated with prevalence of Nobel laureates (Fig. 1).(Messerli, 2012)  These suggest that regular consumption of chocolate may be effective in improving cognitive function in elderly subjects with mild cognitive impairment.(Desideri et al., 2012) 


Considerable research suggests that the consumption of coffee, cocoa, MCT oil, and phosphatidylserine may support cognitive health, reverse cognitive decline in aging individuals, and improve cognitive performance.  A product that combines these ingredients may further support these outcomes and be an effective and marketable product.


Phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly and may reduce the risk of dementia in the elderly** 

Product of USA 

** Very limited and preliminary scientific research suggests that PS may reduce the risk of cognitive dysfunction in the elderly. FDA concludes that there is very little scientific evidence supporting this claim.  Very limited and preliminary scientific research suggests that PS may reduce the risk of dementia in the elderly. FDA concludes that there is little scientific evidence supporting this claim.


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