Research spotlight: Can dietary sources of melatonin have meaningful effects on human health?

Most individuals associate the critical hormone melatonin with the promotion of sleep and regulation of the sleep-wake cycle but less is known about its regulatory roles in other functions that promote anti-inflammatory, antioxidant, immune-enhancing, and metabolic benefits.

Produced primarily by the pineal gland in the brain, melatonin’s synthesis and release is regulated by light cues i.e. melatonin starts to be released at night with diminishing light, peaking between 2-4 am in the morning, and declines with the emerging morning light each day. Other sites of synthesis include the gastrointestinal tract, retina, bone marrow, and immune cells which is thought to contribute to its broader actions and benefits.

 

Dietary sources of melatonin

What we have come to know is that melatonin is also naturally present in low concentrations across most plant and animal tissues where it functions in similar regulatory roles as in humans.  Since this discovery, dietary sources of melatonin have been further explored to determine if they can raise melatonin concentrations in human plasma and whether this can contribute meaningfully to health outcomes.

In evaluating the melatonin content of a breadth of different foods of plant and animal origins, the highest levels in animal foods were found within fish and eggs whilst in plant foods, nuts especially pistachios and walnuts, black and red varieties of rice, tart cherries, grapes, mushrooms, and tomatoes also contained reasonable levels. With beverages, red wine and coffee from roasted coffee beans also contained an appreciable amount of naturally present melatonin.

 

Influence on plasma melatonin

There are several documented examples of how natural dietary sources of melatonin can lead to raised plasma levels in both animals and humans despite relatively low quantifiable levels. In rats fed walnuts, a four-fold increase in baseline melatonin levels was observed whilst in another rat study, consumption of germinated kidney beans significantly altered the melatonin levels in plasma and the excretion of its by-product metabolite in urine (another indicator of altered blood plasma levels of melatonin).

Similar data was observed in human studies. In a study of three groups of healthy volunteers separated by age range, an increase in urinary excretion of the by-product metabolite was observed in all groups after consumption of 200ml of grape juice twice a day (indicating raised plasma levels). Another small human study found volunteers who consumed tropical fruit and their juice (banana, orange, and pineapple), significantly increased their plasma melatonin concentration 2 hours after consumption.

 

The potential role of co-factors

Vitamins from the B complex group and minerals such as magnesium and zinc are also present in many of these foods and are essential co-factors for melatonin synthesis.  Whether the observed results from these studies were directly related to the naturally present melatonin or to the nutritional co-factors required for the body’s own endogenous production are yet to be elucidated.

With the gradual decline of endogenous melatonin production with age, there may be value in the future production of melatonin supplements from dietary sources to support some of its key functions.  As melatonin is rapidly metabolised and eliminated, intake from dietary sources is not considered to be unsafe.

 

Summary

Whether dietary sources of melatonin in supplemental form can have a meaningful effect on human health requires further research.  What these studies do represent is the diversity of natural active constituents including melatonin present in whole foods, their bioavailability in humans, and promising potential for future product development and clinical applications.

 

References

  1. Meng, X et al. Dietary Sources and Bioactivities of Melatonin. Nutrients 2017, 9, 367; doi:10.3390/nu9040367
  2. Perez-Llamas, F et al. Development of a Phytomelatonin-Rich Extract from Cultured Plants with Excellent Biochemical and Functional Properties as an Alternative to Synthetic Melatonin. Antioxidants 2020, 9, 158; doi:10.3390/antiox9020158
  3. Salehi, B et al. Melatonin in Medicinal and Food Plants: Occurrence, Bioavailability, and Health Potential for Humans. Cells 2019, 8, 681; doi:10.3390/cells8070681
  4. Arnao, M; Hernandez-Ruiz, J. The Potential of Phytomelatonin as a Nutraceutical. Molecules 2018, 23, 238; doi:10.3390/molecules23010238
  5. Bonomini, F et al. Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases. Nutrients. 2018, 10, 1135; doi:10.3390/nu10091135

Palmitoylethanolamide’s (PEA) role in the immune response to respiratory viruses including influenza.

Viruses such as influenza and other respiratory viruses activate an immune response in the human body which includes antiviral and pro-inflammatory responses.  The extent of this response is influenced by several factors and explains why one person can experience mild symptoms from the same cold or flu virus whilst another can experience more severe symptoms and illness. Infections with particularly virulent respiratory viruses may also trigger excessive and uncontrolled production of inflammation-producing chemicals contributing to a more severe illness presentation and potential complications.

Palmitoylethanolamide (PEA) is an endogenously produced molecule with well established anti-inflammatory properties for chronic and neuropathic pain. However, it was originally explored as a therapy for the common cold and influenza within six double-blind, placebo-controlled trials in adults and children. These trials were able to demonstrate the efficacy of PEA in both the prevention and treatment of colds and influenza when taken in a supplemental form.

 

Mechanisms of action

PEA is known as an autocoid, a self-produced regulatory molecule made by immune cells to counteract localised inflammation caused by various triggers including injuries, infections or other stressors.

As a critical regulatory molecule, it plays a key role in controlling inflammation-signalling pathways and delivering effective and appropriate immune responses.

Furthermore, PEA has shown an ability to inhibit overactive immune cells such as mast cells in response to viral illnesses, a contributing factor towards respiratory complications.

Through some of these key mechanisms, PEA has demonstrated clinical efficacy in reducing the incidence, severity, and duration of respiratory viral infections of various pathogenic origins in both adult and child populations. 

 

Summary of Clinical Studies

  • 223 factory workers took PEA: 1800mg/day for 12 days and experienced a 45.5% reduction of fever, headache, sore throat, number of sick days after 1 week

 

  • 436 members of an army unit took PEA: 1800mg/day for 8 weeks and experienced 40% lower incidence of acute respiratory disease in PEA group at 6 weeks and 32% lower incidence at 8 weeks compared to placebo

 

  • 901 members of an army unit took PEA: 1800mg/day for 3 weeks + 600mg/day for 6 weeks (Total treatment period of 9 weeks) and experienced a 34% lowering of acute respiratory disease cases in the PEA group vs placebo

 

  • 610 members of an army unit took PEA: 1800mg/day for 3 weeks + 600mg/day for 6 weeks (Total treatment period of 9 weeks) and experienced a 52% reduction of acute respiratory disease cases vs placebo

 

  • 335 members of an army unit took PEA: 1800mg/day for 3 weeks + 600mg/day for 6 weeks (Total treatment period of 9 weeks) and experienced a 63% reduction of acute respiratory disease cases vs placebo

 

  • 196 school children took PEA: 600mg/day for 8 weeks and experienced 15.7% reduction of disease incidence at 8 weeks in the absence of an influenza epidemic period.

 

References

Paladini A, Fusco M, Cenacchi T, et al. Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis. Pain Physician 2016; 19: 11-24

 

Murphy, E. An effective treatment strategy for cytokine storm in severe influenza. American Laboratory. 2017 (Web article)

 

J. M. Keppel Hesslink. Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-α agonist and effective nutraceutical. Journal of Pain Research 2013 (6) 625-634

 

J. M. Keppel Hesselink, Tineke de Boer, and Renger F. Witkamp, “Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold,” International Journal of Inflammation, vol. 2013

 

Disclaimer: This content is intended for general informational purposes and does not aim to address or make claims about any specific health issues. For more information on any of the included content, please contact us the Green Dispensary on 08 8363 7322 or compounding@greendispensary.com.au

Customer Update: COVID-19

Dear Customers,

 

Pharmacies have been deemed as essential services by the Australian government and for the health of the community, will remain at the frontline of the current health pandemic.  To continue to deliver a high level of service, we are committed to the safety and protection of our customers, staff and the most vulnerable in our community.

Under guidance from the Australian government and pharmacy industry bodies with respect to the COVID-19 pandemic, we are taking additional precautionary measures to minimise the spread of the 2019 novel coronavirus as well as continue to ensure fair and equitable access to medicines for all.

Following is an update to current operations across our pharmacies:

  • If you have a cough, sore throat, fever or shortness of breath, please call the pharmacy rather than coming into the store so we can assist you in the best way possible:

 

Green Dispensary Erindale  – 84316727

Green Dispensary Stirling –83391347

Green Dispensary Blackwood –82782388

Green Dispensary Compounding –83637322

 

  • All counters and contact surfaces such as EFTPOS pin pads will be frequently and hygienically cleaned with disinfectant surface spray.

 

  • Our staff is remaining vigilant around their own personal health and wellbeing and undertaking hygiene measures around infection control such as frequent hand sanitisation.

 

  • We have removed all product testers from our stores to reduce transmission risk.

 

  • There is access to hand sanitizer in all customer-facing areas.

 

 

 

Due to the constantly changing circumstances, we will endeavour to provide any critical or relevant updates via our social media (@greendispensarypharmacies) and website (greendispensary.com.au) platforms as they come to hand.

 

We are here to assist you seven days a week for reassurance and advice, medications and health supplies during the COVID-19 pandemic and through working together, we aim to ensure a healthy environment and continued wellbeing for all. Thank you for your continued support, patience, and understanding.

 

Yours in Health,

The Green Dispensary Team

 

**For the latest updates on health information and resources, we encourage you to visit the following websites:

SA Health (https://www.sahealth.sa.gov.au)

Australian Government Department of Health (https://www.health.gov.au)

 

***If you develop a fever, cough, sore throat or shortness of breath within 14 days of overseas travel or since last contact with a confirmed COVID-19 positive patient, contact your doctor or the Coronavirus Information Helpline on 1800 020 080.  For serious symptoms such as difficulty breathing, contact 000 for urgent medical help.

Bushfire Activation 20 January – 29 February 2020

The aftermath of the recent South Australian bushfires will impact for time to come. We’ve chosen to support the incredible efforts of a few organisations which are close to our hearts who have been working both at the frontline and behind the scenes to assist our affected local communities and wildlife.

Our stores will be activating the following initiatives:

*Collecting food and essential supplies for: Foodbank

Bottled water | UHT Milk | Breakfast cereals | Tinned food/meals (with ring pulls) | Pasta, rice, noodles | Grab & Go Snacks eg. Muesli bars | Pet food | Toiletries and personal hygiene products

*Collecting donations via our collection boxes for: SAVEM (South Australian Veterinary Emergency Management)

*Donating five dollars from the sale of every private-labeled Green Dispensary retail product sold for: CFS Foundation

For our Green Dispensary customers and local communities who wish to contribute, we will have all initiatives activated at every Green Dispensary pharmacy including Stirling, Erindale, Blackwood and St Peters until the 29th of February.

Our thoughts and hearts are with all who have been impacted.