Phosphatidylserine and L-ornithine would probably not be the first nutrients that spring to mind when it comes to addressing complaints of stress and sleeplessness, but this article will help to shed some light on why you should prescribe them to certain patients. This article also explores some of the most relevant supplements and pairings for neurotransmitter and hypothalamic-pituitary-adrenal (HPA) axis support.

Phosphatidylserine for Stress

Phosphatidic acid and phosphatidylserine complex (PAS) or phosphatidylserine, taken at a dose of either 300 or 400 mg/day, has been shown to alleviate stress across several double-blind, randomised, placebo-controlled studies. Favourable effects on mood, the feelings of stress¹ and distress,² and on hormones involved in the endocrine stress response (namely cortisol) have been observed in highly stressed individuals.^2,3

Some patients who might fall into this category include university students, businesspeople, parents - especially single parents, those suffering from burnout, or those feeling weighed down by the stress of losing their job, divorce or the loss of a loved one.

L-Ornithine for Ageing Adults, Sleep Problems, Mood, and Memory

In three double-blind, randomised, placebo-controlled studies, in healthy participants up to 61 years of age, ornithine monohydrochloride 500 mg (equiv. L-ornithine 400 mg) per day demonstrated beneficial effects on mood and potentially sleep. Thus, L-ornithine might help some patients struggling with mood and sleep disturbance, though strong evidence to support this theory is lacking. In one of these studies, dim light melatonin onset (DLMO) was delayed by 15 minutes after ingestion of L-ornithine. DLMO is recognised as a marker of central circadian phase.⁴

As we age, our pineal gland naturally produces less melatonin. Consequently, older adults tend to go to sleep and wake up earlier. This is accompanied by other changes in sleep architecture, like getting less deep sleep and waking more frequently throughout the night.^5,6 This new normal can be made even more difficult during the transition into menopause (perimenopause) because of symptoms such as night sweats and other hormonal changes.⁶

By slightly delaying DLMO, L-ornithine could be used to help realign circadian rhythm in older patients who have an internal body clock that is timed too early. It should be considered in those struggling to settle into a suitable sleep schedule due to early evening sleepiness and early morning waking, clinically known as advanced sleep phase disorder (ASPD).⁷

Other research suggests that this patient picture may extend to those with depression, young and old. While circadian advancement (earlier DLMO) and alterations to sleep timing are evident in older people with lifetime major depression,⁸ younger women (18 to 28 yo) with unmedicated major depression are also reported to have advanced DLMO relative to sleep onset, associated with poorer mood. This is consistent with early morning awakenings often seen in depression.^9,10 Such patients may theoretically benefit from L-ornithine, though direct evidence is lacking.

Unlike caffeine or nighttime light exposure that also delay the sleep-wake circadian clock,⁴ L-ornithine does not disturb quality of sleep. In fact, L-ornithine improves sleep quality, as reported in two trials.^11,12 Other findings from these studies included significantly increased sleep length and significantly reduced anger, fatigue, salivary cortisol levels (on awakening) [in flushers the morning after alcohol consumption],¹² and cortisol/dehydroepiandrosterone sulphate (DHEA-S) ratio (in healthy workers)¹¹ in the L-ornithine group, compared to the placebo group. Taken together, improvements in sleep and stress can be expected when taking L-ornithine.

The psychoneuroendocrine interplay of cortisol (stress) and melatonin (sleep) and its effects^13-16 are known to most practitioners but what may not be front of mind is that changes in cortisol and melatonin levels can predict various behavioural symptoms, such as sleep efficiency, physical activity and disinhibition in older adults living with dementia.¹⁷ This alone can justify the use of nutrients that help to support sleep and stress regulation but deserves to be explored in more depth.

Messengers of Brain Health

Brain-derived neurotrophic factor (BDNF) is a neuroprotective protein important in learning, memory and behaviour. BDNF is highly involved in the regulation of HPA axis activity and neuroplasticity, but its levels are altered in the stressed brain.^18-20 Lower levels of BDNF have been associated with depression,²¹ burnout²² and cognitive impairment^22-24 in some studies. And so, enhancing BDNF levels may offer a therapeutic strategy for treating mood disorders²⁵ and even Alzheimer’s disease.^26,27

Each in their own way, L-ornithine, phosphatidylserine, and vitamins B5 and B6 support BDNF synthesis and signalling. These ingredients plus tyrosine also play foundational roles in neurotransmitter and hormone synthesis, notably gamma-aminobutyric acid (GABA), catecholamines (dopamine, adrenaline and noradrenaline) and cortisol. * To review each of their roles and for further information refer to the Eagle Clinical Advanced Nutritional Support For Hypothalamic-Pituitary-Adrenal (HPA) Axis Health tech sheet.

Translating neuroscience to effects relevant to patients is perhaps best exemplified when tyrosine is used as an example. Tyrosine increases dopamine availability that, in turn, can enhance cognitive performance (episodic memory, working memory and fluid intelligence) in those young and old.²⁸

Highly Indicated Companion Products

L-ornithine, phosphatidylserine, vitamins B5 and B6, and tyrosine can be co-prescribed with a range of other nutrients, perhaps none more important than magnesium. Stress increases magnesium loss, causing a deficiency and, in turn, magnesium deficiency worsens susceptibility to stress.²⁹ On the other hand, a clinical trial has shown greater benefit of magnesium combined with vitamin B6 in adults experiencing severe/extremely severe stress, compared to magnesium alone.³⁰ Moreover, magnesium supplementation has been shown to significantly increase sleep time, sleep efficiency and serum melatonin; significantly decrease sleep onset latency and serum cortisol concentrations; and marginally reduce early morning awakening in elderly individuals with insomnia.³¹

Multivitamin, mineral and amino acid complexes, particularly B group vitamins, also benefit stressed individuals.^32,33 Glycine would be well placed to support the relief of insomnia, having been shown to improve subjective sleep quality and sleep efficacy, shorten sleep onset latency, lessen daytime sleepiness, and improve performance on memory recognition tasks.³⁴

L-theanine is another highly indicated companion product for patients experiencing stress and sleeplessness.^35-39

Nutrient-Only Formulations Allow for Flexible Herbal Prescribing

So far, this discussion has only captured the most pertinent nutritional prescriptions; however, herbs are equally deserving of merit and attention.

Practitioners dispensing herbal remedies have the luxury of prescribing nutritional products alongside herbal tinctures or supplements. One might even choose to dispense a ‘day mix’ to support energy production and a ‘night mix’ to promote relaxation, complementing circadian rhythm fluctuations.

The list of adaptogens, adrenal tonics, anxiolytic, sedative, hypnotic, nervine tonic, thymoleptic, cognition enhancing, and neuroprotective herbs suitable for stressed and sleepless patients is long and is not defined by these complaints alone. For example, herbs with a crossover of analgesic and sedative actions may refine this list down to Californian Poppy, Jamaican Dogwood, Kava, and/or Corydalis for patients experiencing insomnia and dysmenorrhoea, or insomnia and lower back pain. Remember, treating the patient is key.

On that note, a holistic treatment plan should be complete with advice on sleep hygiene around a consistent bedtime, natural light exposure and/or light therapy, exercise, social activity, stress management, and of course diet and nutrition. Practitioners should also review the patient’s intake of caffeine and use of other stimulants, alcohol and drugs.⁵

Treating the Cause, Helping the Patient

L-ornithine, phosphatidylserine, vitamins B5 and B6, and tyrosine plus other indicated nutrients (especially magnesium and other B group vitamins) and herbs, ought to feature in the treatment of sleep-, mood- and energy-related complaints. Such a prescription is best suited to highly stressed individuals and older adults suffering from disturbed sleep.

Taken even further, and connecting the dots between sleep and its effects on overall brain health, symptoms such as irritability, depressed mood and memory problems could be nipped in the bud by supporting quality sleep and reducing the physiological impact of stress on the brain.

References

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