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Poor sleep is a common issue for many.  Look at the numbers:
  • Adults who were short sleepers (less than 7 hours per 24-hour period) were more likely to report ten chronic health conditions compared to those who got enough sleep (7 or more hours per 24-hour period)
  • Adolescents need 8 to 10 hours of sleep per night.[i] But, more than two-thirds of U.S. high school students report getting less than 8 hours of sleep on school nights (see Table 4)[ii]
  • 50-70 Million Americans have a sleeping disorder[iii]
Poor sleep is directly connected to your health, too.  Adults who were short sleepers (less than 7 hours of sleep per 24-hour period) were more likely to report being obese, physically inactive, and current smokers compared to people who got enough sleep (7 or more hours per 24-hour period).[iv] Poor sleep also wreaks havoc on your immune system.  Research shows us the association between short sleep duration and infection risk.[v]  ONE night of total sleep deprivation can decrease essential immune cell function.[vi] Simultaneously, prolonged sleep curtailment and the accompanying stress response produce immunodeficiency.[vii]  Lack of sleep is directly linked to decreased immune cells and overall immune cell activity.[viii] This is no joking matter.  Combining the number of people who do not sleep well and the negative impact on immune health, we can see this is no laughing matter.

Understanding the 4-Phases of Sleep

There are four phases of sleep.
Non-Rapid Eye Movement (NREM) (first three stages)
  1. N-1- Light Sleep (1-5 minutes)
  2. N-2- Light Sleep (10-60 minutes)
  3. N-3- Deep Sleep (20-40 minutes) (Repair phase)
    • Regrowing Tissue
    • Strengthen Immune System
    • Build Bone and Muscle
  4. Rapid Eye Movement (REM) (10-60 Minutes)
The body cycles through all stages 4-6 times per night and 75% of sleep should be spent N-REM
While all four are important, the 3rd phase (N-3-Dep Sleep) is extremely important for our topic of immune health. This phase is often referred to as the “restorative” sleep phase.

Natural Solutions for Poor Sleep

Concerning sleep, there are many clinically proven ingredients from which to choose.
Below are some of the more popular sleep supplements available.  Choosing the right one can be imperative for those with immune challenges.  Depending on your sleep issues, combining ingredients that work across multiple phases may be necessary. This means that you may have trouble falling asleep and, therefore, need a supplement to decrease “sleep latency” (the time it takes to fall asleep), i.e., it works best in N-1 and N-2.  For our topic today, I suggest looking for supplements that fall into the “improve restorative sleep” category.
  • 5-HTP- known to increase REM sleep[ix]
  • GABA (PharmaGABA®)- targets GABAA receptors – increases REM sleep 99.6% and NREM 20.6%[x]
  • L-theanine (Suntheanine®)- Decreases Stage 1 and increases Stage 4[xi]
  • Magnesium- magnesium intake increased levels of melatonin and reduced levels of cortisol[xii]
  • Melatonin- REM sleep lasts longer; melatonin levels are lowest in stage 3 and highest in REM[xiii]
  • PEA (Levagen®+)- Decrease Pain, Increase NREM sleep[xiv]
  • Passionflower- inhibits the uptake of gamma-aminobutyric acid (GABA) into neuronal synapses and has an affinity for GABA(A) and GABA(B) receptors [xv]
  • Saffron (affron®)- supports the body’s melatonin production, helps with stress, and increases restorative sleep
  • Valerian- increases stages 3 & 4 while decreasing stage 1[xvi]
  • Xylaria nigripes/Cuscuta chinensis/Panax notoginseng (Zylaria®)- Research with Zylaria has shown it impacts the natural production of GABA, increasing REM sleep
  • Zea Maize (MaizinolTM)- Supports melatonin production, Increases Restorative Sleep NREM)

Immune Support

While sleep is critical to support your immune system, it wouldn’t hurt to add a supplement to support your immune system and sleep aid.  First, we need to discern what type of immune support we are trying to achieve.  Which one of these is you?
  1. A person thinks they are “coming down with something”—they need something to stimulate their immune response.
  2. A person has a chronic immune weakness such as allergies, colds, flu, etc. —they need something for long-term support of their immune functionality.
  3. A person has an autoimmune or overactive immune response—they need something to modulate or even downregulate their immune function.
  4. A person has chronic inflammation such as joint pain, cardiovascular problems, etc.—they need something to support the body’s response to inflammation (inflammation is an initial response by the immune system to harm from physical trauma, bacteria, virus, etc.)
Of these categories, the first two are what most are thinking about when a product is touted as an immune health product.  You are either sick and need acute help to stimulate the immune system or look for long-term benefits to support the immune system and its functionality.  The following are examples of both short and long-term nutraceutical ingredients for immune health.  Remember these are just a few of the numerous immune support ingredients with scientific substantiation.
The following are the top supplements which fit into these two categories:

Short-term:

  • Vitamin C- acts by increasing key immune cells activity, function, mobility, and production.[xvii] [xviii][xix] In general, high doses of vitamin C need to be consumed daily to activate the immune system. Products containing small amounts of vitamin C, i.e., under 1000mg per dose, provide little to no benefit to a person seeking an immediate immune response.
  • Echinacea– acts by activating many critical cells involved with a healthy immune response to infection.[xx] While echinacea often gets negative feedback, it is a good choice for someone seeking a quick way to rev up their immune system.
  • Elderberry- has several effects, including antiviral and immunomodulating effects. Immunomodulating ingredients enhance the body’s immune response.  This can either stimulate or suppress the immune system and may help the body fight abnormal cell production, infection, or other conditions.  Elderberry has also shown it can inhibit the replication of several strains of influenza viruses A and B[xxi], inhibits H1N1 “swine” flu[xxii].  One unique property of Elderberry is that it is a botanical extract that has both acute and long-term benefits for immune health.
  • Zinc– is essential for several types of immune cell functionality.[xxiii]. For acute use, zinc appears beneficial when used orally as a lozenge and taken frequently throughout the day[xxiv], not in one large dose that is swallowed whole.
Long-term:
  • 1,3/1,6 Beta Glucan (Wellmune), 1,3 Beta Glucan (BioGlena) or 1,3/1,6 Beta-Glucan from yeast plus postbiotic rich selenium and zinc (ABB C1®) – Beta glucans help to increase the cells known to “eat” abnormally cells in the body, increase the communication between immune cells and support the release of compounds which help fight off unhealthy cells in the body i.e., viruses, bacteria and abnormal cells produced by the body.[xxv] The combination of 1,3/1,6 Beta-Glucan from yeast plus postbiotic-rich selenium and zinc (ABB C1®) shows it positively impacts trained immunity.
  • Aloe & Rosemary (Symetrian)- Clinically shown to promote rapid immune cell activation and production of key immune cells and the all-important IgG antibodies.
  • ImmunoLin®- Clinically proven to support the immune system and gut health. It helps to neutralize key antigens which can cause infections.
  • Olive Leaf Extract (Olivactive®)- Helps support the immune system in multiple ways by increasing key immune cells to improve immune system response.
  • Probiotics- the beneficial impact of probiotics is by different mechanisms. These mechanisms include the probiotics’ capacity to increase the intestinal barrier function, prevent pathogenic (illness-causing) bacterial movement, and modulate inflammation.[xxvi] Since it is estimated that 70% of immunity originates in the gut, having a healthy microbiome will play a positive role in immune support.
  • Vitamin D- Numerous published clinical studies confirm that low vitamin D levels are associated with an increased risk of infections[xxvii]. National Institute of Health warned that low vitamin D levels are associated with frequent colds and influenza.[xxviii]   For vitamin D to be beneficial, it is advisable to get vitamin D testing done to ensure the proper amounts are consumed.

Combining sleep and stress ingredients with immune support ingredients for a powerful psycho-immunological impact

During these challenging times of increased mental wellness problems and immune health concerns, it would be beneficial to consider combining dietary supplement ingredients for both areas.   A great example would be a product combining one or more of the immune support ingredients with one or more sleep ingredients to be taken at bedtime.  This way, we achieve improved immune system support and sleep.

[i] Paruthi S, Brooks LJ, D’Ambrosio C, et al. Recommended amount of sleep for pediatric populations: a consensus statement of the American Academy of Sleep Medicine. J Clin Sleep Med. 2016;12(6):785–786.

[ii] Wheaton AG, Olsen EO, Miller GF, Croft JB. Sleep duration and injury-related risk behaviors among high school students — United States, 2007–2013. MMWR Morb Mortal Wkly Rep. 2016;65:337–341.

[iii] American Sleep Association Website “Sleep and Sleep Disorder Statistics” https://www.sleepassociation.org/about-sleep/sleep-statistics/

[iv] CDC Website “Data and Statistics Sleep” https://www.cdc.gov/sleep/data_statistics.html ,May 2 2017 Accessed July 9, 2019

[v] Besedovsky L, Lange T, Haack M, The Sleep-Immune Crosstalk in Health and Disease,  Physiological Reviews  99: 1325–1380, 2019

[vi] Morey JN, Boggero IA, Scott AB, Segerstrom SC. Current Directions in Stress and Human Immune Function. Curr Opin Psychol. 2015;5:13‐17. doi:10.1016/j.copsyc.2015.03.007

[vii] Besedovsky L, Lange T, Born J. Sleep and immune function. Pflugers Arch. 2012;463(1):121‐137. doi:10.1007/s00424-011-1044-0

[viii] Besedovsky L, Lange T, Haack M, The Sleep-Immune Crosstalk in Health and Disease,  Physiological Reviews  99: 1325–1380, 2019

[ix] Morrow JD; Vikraman S; Imeri L; Opp MR. Effects of serotonergic activation by 5-hydroxytryptophan on sleep and body temperature of C57BL/6J and interleukin-6-deficient mice are dose and time related. SLEEP 2008;31(1):21-33.

 

[x] Kim S, Jo K, Hong KB, Han SH, Suh HJ. GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharm Biol. 2019 Dec;57(1):65-73. doi: 10.1080/13880209.2018.1557698. PMID: 30707852; PMCID: PMC6366437.

 

[xi] Kim S, Jo K, Hong KB, Han SH, Suh HJ. GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharm Biol. 2019 Dec;57(1):65-73. doi: 10.1080/13880209.2018.1557698. PMID: 30707852; PMCID: PMC6366437.

 

[xii] Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci. 2012;17(12):1161-9.

 

[xiii] Luboshitzky R, Lavi S, Lavie P. The association between melatonin and sleep stages in normal adults and hypogonadal men. Sleep. 1999 Nov 1;22(7):867-74. doi: 10.1093/sleep/22.7.867. PMID: 10566905.

 

[xiv] Rao A, Ebelt P, Mallard A, Briskey D. Palmitoylethanolamide for sleep disturbance. A double-blind, randomised, placebo-controlled interventional study. Sleep Sci Pract. 2021;5(1):12. doi: 10.1186/s41606-021-00065-3. Epub 2021 Sep 10. PMID: 34522787; PMCID: PMC8428962.

 

[xv] Guerrero FA, Medina GM. Effect of a medicinal plant (Passiflora incarnata L) on sleep. Sleep Sci. 2017 Jul-Sep;10(3):96-100. doi: 10.5935/1984-0063.20170018. PMID: 29410738; PMCID: PMC5699852

[xvi] Daniel J. Buysse, Shachi Tyagi, Chapter 42 – Clinical Pharmacology of Other Drugs Used as Hypnotics,, Principles and Practice of Sleep Medicine (Sixth Edition), Elsevier, 2017,Pages 432-445.e7,  https://doi.org/10.1016/B978-0-323-24288-2.00042-8

[xvii] Leibovitz B, Siegel BV. Ascorbic acid and the immune response. Adv Exp Med Biol 1981;135:1-25.

 

[xviii] Vilter RW. Nutritional aspects of ascorbic acid: uses and abuses. West J Med 1980;133:485-92

 

[xix] Smogorzewska, E. M., Layward, L., and Soothill, J. F. T lymphocyte mobility: defects and effects of ascorbic acid, histamine, and complexed IgG. Clin.Exp.Immunol. 1981;43(1):174-179

 

[xx] Manayi A, Vazirian M, Saeidnia S. Echinacea purpurea: Pharmacology, phytochemistry, and analysis methods. Pharmacogn Rev. 2015;9(17):63–72. doi:10.4103/0973-7847.156353

 

[xxi] Zakay-Rones Z, Varsano N, Zlotnik M, et al. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med 1995;1:361-9

 

[xxii] Roschek B, Fink RC, McMichael MD, et al. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry 2009;70:1255-61.

 

[xxiii] Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 1998;68:447S-63S.

 

[xxiv] Mossad SB, Macknin ML, Medendorp SV, Mason P. Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study. Ann Intern Med 1996;125:81-8

 

[xxv] Stier, H., Ebbeskotte, V. & Gruenwald, J. Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan. Nutr J 1338 (2014). https://doi.org/10.1186/1475-2891-13-38

 

[xxvi] Plaza-Díaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A. Immune-Mediated Mechanisms of Action of Probiotics and Synbiotics in Treating Pediatric Intestinal Diseases. Nutrients. 2018;10(1):42. Published 2018 Jan 5. doi:10.3390/nu10010042

 

[xxvii] Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E, Epidemic influenza and vitamin D., Epidemiol Infect. 2006 Dec; 134(6):1129-40.

 

[xxviii] National Institutes of Health. Low Vitamin D Levels Associated with Colds and Flu. NIH website. https://www.nih.gov/news-events/nih-research-matters/low-vitamin-d-levels-associated-colds-flu. Published March 9, 2009. Accessed March 19, 2020