Sponsored By
Sandy Almendarez

November 8, 2012

8 Min Read
Fat Head

Fat-based ingredients, such as omega-3 essential fatty acids and the phospholipids phosphatidylserine (PS) and alpha-glyceryl phosphoryl choline (A-GPC), can help brain health in myriad waysfrom development to mood.

The effects of polyunsaturated fatty acids (PUFAs) on the inflammatory process may impact progression of neurodegenerative diseases, according to a 2010 review.1 Researchers noted omega-3 PUFAs exert an anti-inflammatory effect on neuronal cell membranes, and have the ability to regulate prostaglandin and inflammatory cytokine production. They suggested greater levels of omega-3s in the diet could downregulate brain inflammation and protect against neurodegenerative conditions.

Another 2010 study reported omega-3s regulate brain energy levels by affecting glucose delivery and metabolism.2 Researchers at the French National Institute for Agriculture Research (INRA) said when exposed to the omega-3s DHA and eicosapentaenoic acid (EPA) or the omega-6 arachidonic acid (AA), rat brain endothelial cells rapidly incorporated the essential fatty acids (EFAs) into their membrane phospholipids. Therefore, they concluded physiological doses of omega-3 EFAs may positively impact glucose transport and utilization by cerebral cells.

An April 2012 study found people with higher intakes of omega-3 EFAs, vitamins C, D and E, and the B vitamins were less likely to have brain shrinkage associated with Alzheimers disease than people who had lower levels.3 Those nutrients were also associated with higher scores on mental thinking tests. The study involved 104 people (average age of 87) and with few risk factors for memory and thinking problems.

However, a widely publicized Cochrane Dementia and Cognitive Improvement Group review in June 2012 said supplementation with omega-3s showed no effect on the incidence of dementia in cognitively healthy older people.4 Researchers examined three randomized controlled trials of omega-3 long-chain PUFA intervention in 4,080 participants. In two studies involving 3,221 participants, the researchers reported no differences between the omega-3 and placebo group in mini-mental state examination score at final follow-up (following 24 or 40 months of intervention). In two studies involving 1,043 participants, other tests of cognitive function, such as word learning, digit span and verbal fluency, showed no beneficial effect of PUFA supplementation. Participants in both the intervention and control groups experienced either small or no cognitive declines during the studies.

However, this review did not include studies that assessed the effects of omega-3 supplementation for the prevention of dementia and cognitive decline, which are available, according to Harry B. Rice, Ph.D., vice president, regulatory and scientific Affairs, Global Organization for EPA and DHA Omega-3s (GOED). Rice noted the MIDAS5 (Memory Improvement With Docosahexaenoic Acid Study), published in 2010, demonstrated that 24-week supplementation with 900 mg/d DHA improved learning and memory function in age-related cognitive decline.5

Additionally, Aker BioMarine reported krill oil, which has omega-3s attached to phospholipids, had positive effects on children with attention deficit hyperactivity disorder (ADHD) in a pilot study conducted on 20 boys between 7 and 12 years of age in Reykjarvik, Iceland. The boys took 4 g/d of krill oil for 13 weeks, and they experienced positive effects on attention, distraction, hyperactivity, irritability, anger and communication.

PhosphatidylSerine (PS), a phospholipid component found in meats and some vegetables, assists proteins that manage membrane functions and helps funnel waste products out of cells. FDA granted two health claims for PS indicating that it may reduce the risk of cognitive dysfunction and dementia in the elderly. "May reduce" is key to that health claim, as PS is not a drug and marketing can't say it cures or treats diseases.

Soybean-derived PS improved memory function in the elderly with memory complaints after six months of use at 300 mg/d in one double blind, randomized controlled study.6 Seventy-eight elderly people with mild cognitive impairment (50 to 69 years old) were randomly allocated to take soy-PS or placebo. The memory improvements in the soy-PS-treated group was mostly attributed to the increase in delayed verbal recall.

Another 2007 review from Italy said inhibition of endogenous acetylcholine degradation through cholinesterase inhibitors, such as PS, represents a "milestone in symptomatic treatment of cognitive symptoms in mild to moderate stages of Alzheimer's disease."7

PS significantly increased cognitive function prior to exercise in a study that noted the natural ingredient could improve cognitive function in athletes and non-athletes alike.8 In this randomized, double blind, placebo-controlled, crossover study, 18 resistance-trained males, aged 18 to 30, ingested 400 mg/d of soy-derived PS (as SerinAid® from Chemi Nutra) for 14 days or a placebo. PS supplementation significantly reduced the time needed for a correct calculation on the Serial Subtraction Test (SST), a method in which subjects repeatedly subtracted the number seven from a random four-digit number, by 20 percent, reduced the total amount of errors by 39 percent and increased the amount of correct calculations by 13 percent prior to or in response to exercise compared to placebo.

PS can also help those on the other end of the age spectrum. A Japanese study showed 200 mg/d of PS reduced ADHD symptoms in children aged 6 to 12, as demonstrated by the results of DSM-IV diagnostic criteria, visual perception test, learning disorder checklist (hearing, speaking, reading, writing, calculation and inference) and continuous performance tests.9

An unpublished double blind study from Kaplan Hospital, Rehovot, Israel, noted 300 mg/d of PS for three months improved memory and mood in subjects aged 60 to 80 years old. Components of memory and cognition that were most improved by the treatment included memorizing information, visual memory and memorizing numbers.

Another phospholipid A-GPC increases formation of the neurotransmitter acetylcholine, which plays an important role in cognitive function. The Institute of Internal Medicine and Geriatrics, University of Palermo, Italy, found A-GPC increased psychic recovery in stroke victims. In the study,  71 percent of the patients reached "no cognitive decline" or "forgetfulness" when 1 g/d of it was injected after the stroke for 28 days, and then 400 mg tid was taken orally during the following five months.10

At the First Neurological Clinic, University of Messina, Italy, researchers reported A-GPC given intramuscularly at 1 g/d for 90 days to patients with mild to moderate vascular dementia produced a definite symptomatic improvement.11 A-GPC is also helpful for those who suffer from the trauma of craniocerebral injury (CCI), which produces metabolic disturbances such as mixed ischemic-hypoxic, oxidative, inflammatory and excitotoxic cascades. When 23 patients with CCI were treated with A-GPC intramuscularly with 1 g/d for 14 days, and then 0.8 g/d orally for the next 28 days, an improvement was noted in 96 percent of the patients.12

A 2003 multicenter, double blind, randomized, placebo-controlled trial found patients affected by mild to moderate dementia of the Alzheimer type who were treated with A-GPC (400-mg capsules) for three months had better scores on Alzheimer's tests than patients who took a placebo.13 A 1993 multicenter, randomized, controlled study reported A-GPC improved most neuropsychological parameters as measured by behavioral scales and psychometric tests in patients with probable senile dementia of Alzheimer's type of mild to moderate degree.14

Discover which brain health ingredients can formulate seamlessly in your new supplement, food or beverage at SupplySide West.

Find more information on brain health in INSIDER's Cognitive Content Library.

References listed on the next page.


1.       Layé S. "Polyunsaturated fatty acids, neuroinflammation and well being." Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):295-303.

2.       Pifferi F et al. "n-3 long-chain fatty acids and regulation of glucose transport in two models of rat brain endothelial cells." Neurochem Int. 2010 Apr;56(5):703-10.

3.       Annweiler C et al. " Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging." Neurology. 2012 Apr 17;78(16):1281

4.       Sydenham E et al "Omega 3 fatty acid for the prevention of cognitive decline and dementia." Cochrane Database Syst Rev. 2012 Jun 13;6:CD005379.

5.       Yurko-Mauro K. " Memory improvement with docosahexaenoic acid Study (MIDAS)" Curr Alzheimer Res. 2007 Dec;4(5):553-5.

6.       Kato-Kataoka A et al. "Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints." J Clin Biochem Nutr. 2010 Nov;47(3):246-55.

7.       Parnetti L et al. "Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?" J Neurol Sci. 2007 Jun 15;257(1-2):264-9.

8.       Parker, A et al. " The effects of phosphatidylserine supplementation on cognitive functioning prior and following an acute bout of resistance training in young males." J Int Soc Sports Nutr. 2010 Sept 15;7(Suppl 1):P2 DOI:10.1186/1550-2783-7-S1-P2

9.       S. Hirayama,Y; Masuda,R; Rabeler. "Effect of Phosphatidylserine administration on symptoms of attention-deficit/hyperactivity disorder in children." AgroFOOD. 2006 Sept/Oct;17(5):17-21

10.   Barbagallo Sangiorgi G,  et al. " alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial." Ann N Y Acad Sci. 1994 Jun 30;717:253-69.

11.   Di Perri R, et al. " A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia." J Int Med Res. 1991 Jul-Aug;19(4):330-41.

12.   Mandat T et al. "[Preliminary evaluation of risk and effectiveness of early choline alphoscerate treatment in craniocerebral injury]. [Article in Polish]" Neurol Neurochir Pol. 2003 Nov-Dec;37(6):1231-8.

13.   De Jesus Moreno Moreno M. " Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial." Clin Ther. 2003 Jan;25(1):178-93.

14.   Parnetti L et al. " Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer's type." Drugs Aging. 1993 Mar-Apr;3(2):159-64.

About the Author(s)

Sandy Almendarez

editor in chief, Informa

Sandy Almendarez entered the natural products industry in 2009 when she joined Virgo Publishing (now Informa Exhibitions) as an assistant editor. Since then, she's worked her way up to editor in chief where she writes, edits and manages content for INSIDER. Under Sandy’s direction, INSIDER has won editorial awards from Folio: every year since 2014, including B2B Editorial Team of the Year in 2015.

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