Fatty acid blend soothes the stressed brain

Protect the Brain from Stress with a Unique Lipid Blend

Fatty Acid Blend Soothes the Stressed Brain

Your brain is at least 60% pure fatty acids. These crucial molecules are necessary for your brain to perform its many functions.1 They include phospholipids, which compose the cell membrane of every neuron. Among those phospholipids, phosphatidylserine plays a special role. The sheath around your nerve cells, composed of myelin, is rich in phosphatidylserine.2 Phosphatidylserine supports memory in all its forms—both short- and longterm memory, as well as the ability to retrieve memories. Phosphatidylserine is critical to attention, concentration, problem solving, and communication. It especially supports rapid reactions and reflexes.3 It also helps protect the body and brain against stress.4 Oral phosphatidylserine is highly bioavailable and readily crosses the blood-brain barrier.5

A hallmark of the aging brain is the decreased ability to adapt to stress— including heat, cold, and chronic stress.6 Not only does age reduce stress resilience, chronic stress can accelerate the aging process, according to renowned neuroendocrinologist Robert Sapolsky, PhD, of Stanford University.7 The adrenal cortex secretes glucocorticoids in response to a variety of stressors.8 Glucocorticoids signal the brain, which then initiates a cascade of signals that may increase blood pressure and carbohydrate metabolism, as well as hormones, to improve energy and alertness. Sapolsky has found that the adrenocortical axis, which is central to the stress response, can be impaired with aging. After experiencing stress, the aged brain may continue to stimulate the secretion of stress hormones and cortisol. That continual glucocorticoid exposure can actually further impair the brain. Sapolsky calls this a “feed-forward cascade,” with potentially serious consequences. Excess secretion of cortisol is linked to depression, anxiety disorders, and metabolic syndrome (a precursor to diabetes and heart disease). Impaired cortisol secretion is linked to numerous chronic conditions, including fatigue, pain, irritability, fibromyalgia, arthritis, and chronic fatigue syndrome.9 One hallmark of aging in the human brain is decreased phosphatidylserine in the membranes of neurons.10,11,12 Given these links

between stress, aging, cortisol, and phosphatidylserine, researchers began to investigate the possibility that phosphatidylserine could act as a buffer against stress. Indeed, they soon found that it could decrease cortisol responses to acute physical and mental stress.13

One hallmark of aging in the human brain is decreased phosphatidylserine in the membranes of neurons.

A Blend of Phosphatidylserine and Phosphatic Acid Buffers Against Stress

Given the numerous studies on phosphatidylserine and stress, researchers have looked at the possible synergistic effect of a blend of phosphatidylserine with phosphatidic acid (PA), a precursor for other regulatory lipids.14 Phosphatidic acid also acts as signaling lipid, increasing in response to stress.15 Together, phosphatidic acid and phosphatidylserine can reduce cortisol levels and enhance stress resilience.16

A 2004 randomized, double-blind, placebo-controlled study found that a mixture of phosphatidylserine and phosphatic acid, a lipid messenger molecule, provides protection against stress.16 80 individuals (40 men and 40 women, aged 20–45) received the lipid blend (PAS) at either 400, 600, or 800 mg daily for three weeks. Each 100 mg PAS capsule contained 100 mg of phosphatidylserine and 125 mg of phosphatic acid, plus 270 mg of other phospholipids (phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, and others).

All volunteers were given a test to trigger a moderate amount of anxiety. Called the Trier Social Stress Test, it entails a mock job interview, a five-minute speech, and a fiveminute math challenge, all performed in front of two observers. Though both groups experienced stress (increased heart rate and elevated scores on a questionnaire regarding anxiety and mood), those receiving 400 mg/day of PAS had significantly lower levels of

stress hormones such as cortisol and adrenocorticotropic hormone (ACTH) in their saliva. This was the only effective dose—600 and 800 mg did not significantly impact stress hormones. A second study in 2014 confirmed the efficacy of 400 mg of PAS on stress.17 75 healthy male volunteers were enrolled in this double-blind, placebocontrolled study and randomly assigned to placebo, 200 mg of PAS, or 400 mg of PAS for 42 days. Before the experiment began, they were given a test to measure chronic stress levels. Stress was induced via the Trier Social Stress Test. In those individuals who had tested high on chronic stress, a daily dose of 400 mg of PAS was effective

in normalizing salivary and serum cortisol responses as well as adrenocorticotropic hormone (ACTH), which is secreted by the anterior pituitary gland in the brain and regulates levels of cortisol. PAS 200 and placebo were not effective. PAS supplementation had no significant effect on heart rate, pulse transit time, or psychological stress response.

A mixture of phosphatidylserine and phosphatic acid, a lipid messenger molecule, provides protection against stress.… Individuals receiving 400 mg/day of PAS (lipid blend of phosphatidylserine and phosphatic acid) had significantly lower levels of stress hormones in their saliva.

It is notable that 400 mg of PAS was effective in both studies, whereas 200, 600, and 800 mg were not. This is, according to lead author Juliane Hellhammer, PhD, an “inverse U-shape reaction, a quite common finding. More is not always better in terms of efficacy.”18

In related research, PAS has been found to improve memory and mood in elderly individuals. One three-month, double-blind, placebocontrolled trial in functioning, nondepressive elderly people with memory problems, found that a blend of 100 mg phosphatidylserine and 80 mg phosphatidic acid three times daily improved mood and cognition.19 A second unpublished study, a twomonth randomized, double-blind, placebo-controlled trial, found that the same dose of PAS three times daily significantly improved memory and prevented “winter blues” in patients with Alzheimer’s disease (AD). This is not surprising, given the correlations between the aging brain and resilience to stress. As the researchers note, “The data encourage long-term studies ... in AD patients and other elderly with memory or cognition problems.” PAS may have broader effects on other conditions impacted by stress, such as premenstrual syndrome. PMS patients have been shown to have lower cortisol concentrations premenstrually as compared to those without PMS.20 According to Dr. Hellhammer: “We just submitted a publication with very convincing data titled: A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces symptoms of the premenstrual syndrome (PMS): results of a randomized, placebocontrolled, double-blind clinical trial.”18

Today, when novel concerns and ways of interacting are ratcheting up our stress levels, it’s good to know there are nutrients that can help shore up our resilience, both physical and mental.21 

2 Svennerholm L. Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res. 1968;9(5):570-9. PMID: 4302302

3 Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition. 2015;31(6):781-6. PMID: 25933483

4 Benton D, Donohoe RT, Sillance B, et al. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci. 2001;4(3):169-78. PMID: 11842886

5 Rosadini G, Sannita WG, Nobili F, et al. Phosphatidylserine: Quantitative EEG effects in healthy volunteers. Neuropsychobiology. 1990-1991;24(1):42-8. PMID: 2132640

6 Sapolsky RM, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascadehypothesis. Endocr Rev. 1986;7(3):284-301. PMID: 3527687

7 Sapolsky, RM. Stress, the Aging Brain, and the Mechanisms of Neuron Death. Cambridge, MA: Bradford Books-The MIT Press; 1992.

8 Munck A, Guyre P, Holbrook N. Physiological functions of glucocorticoids during stress and their relation to pharmacological actions. Endocr Rev. 1984 Winter;5(1):25-44. PMID: 6368214

9 Nicolaides NC, Kyratzi E, Lamprokostopoulou A, et al. Stress, the stress system and the role of glucocorticoids. Neuroimmunomodulation. 2015;22(1-2):6-19. PMID: 25227402

10 Crook TH, Tinklenberg J, Yesavage J, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41(5):644-9. PMID: 2027477

11 Ball MJ. Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study. Acta Neuropathol. 1977;37(2):111-8. PMID: 848276

12 Lippa AS, Critchett DJ, Ehlert F, et al. Age related alterations in neurotransmitter receptors: An electrophysiological and biochemical analysis. Neurobiol Aging. 1981;2:3-8. PMID: 6115325

13 Monteleone P, Beinat L, Tanzillo C, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology. 1990;52:243-48. PMID: 2170852

14 Athenstaedt K, Daum G. Phosphatidic acid, a key intermediate in lipid metabolism. Eur J Biochem. 1999;266:1-16. PMID: 10542045

15 Sergeant S, Waite KA, Heravi J, et al. Phosphatidic acid regulates tyrosine phosphorylating activity in human neutrophils: enhancement of Fgr activity. J Biol Chem. 2000;276:4737-46. PMID: 11078731

16 Hellhammer J, Fries E, Buss C, et al. Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress. 2004;7(2):119-26. PMID: 15512856

17 Hellhammer J, Vogt D, Franz N, et al. A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebocontrolled study. Lipids Health Dis. 2014;13:121. PMID: 25081826

18 Personal communication, 2017 Jul 21.

19 Moré MI, Freitas U, Rutenberg D. Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer’s disease and dementia. Adv Ther. 2014;31(12):1247-62. PMID: 25414047

20 Girdler SS, Pedersen CA, Straneva PA, et al. Dysregulation of cardiovascular and neuroendocrine responses to stress in premenstrual dysphoric disorder. Psychiatry Res. 1998;81(2):163-78. PMID: 9858034

21 American Psychological Association. Stress in America [Internet]. Washington, DC: American Psychological Association; 2017 [cited 2017 Aug 7]. Available from: http://www.apa.org/news/press/releases/stress/index.aspx

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