Glymphatic system – yes- sleep helps protect against Alzheimer’s dementia

Following up on Friday’s easy answer day (previous post) – yes, the glymphatic system of the brain does help protect against Alzheimer’s dementia, (7, 8, 14, 17), and sleep, especially one of the deeper stages of sleep (low-delta), is important. (10, 11, 13) Sleeping on your right side may help promote better fluid drainage through the glymphatic system of the brain (sleeping on your right side puts the left side of your body with your heart farther up above the rest of your body, a pillow between your knees and a neck support may also help). (Social media link, reference source: Neurology Reviews, 2) (12) The circulation by the heart can help move fluid through the brain but only indirectly due to the on/off pressure of the arterial pulse. The regular lymphatic system of the body is a drainage system for the brain fluid system but the blood brain barrier prevents direct interaction. Specialized water pumps in some types of brain glial cells help provide circulation within the brain by pumping water in two directions within the second layer of thick membranes that separate the soft brain tissue from the bony skull. (3)(4)(15)(16)

Overall the fluid within the brain does circulate and there is a visible, small, pulsing movement that has been amplified and can be observed in a video: (5). The spread of a dye within the brain can be observed in a different type of brain scan, the fluid diffusion is not rapid taking 24 hours to reach a maximal point, and the movement of the dye was most prevalent (see color chart) near the skull: (6). The glymphatic system as defined as the specialized glial cells with water pump channels is located in the area near the skull. (4) Diffusion of fluid throughout deeper areas of the brain where the blood brain barrier is not found can occur to a small extent through membranes. (9)

Exercise may also help the glymphatic system function better. (18) The lymphatic vessels and lymph nodes in the neck are the initial drainage route for the glymphatic system cleansing of the various fluid filled areas of the brain. Stretching exercises and rhythmic walking type exercise can help move lymphatic fluid from farther areas of the body to the torso and urinary system for eventual excretion.

Small amounts of alcohol – one third of a serving; to moderate – one or two servings per day (too much may not be helpful); may help the detoxification of the brain fluid by mechanisms that are not well understood yet but which seem to involve the glymphatic system. (19, 20) The mechanism may involve the effect of alcohol on GABA receptors, it can activate them which in general would have a calming/inhibitory effect, (23), however GABA receptors also are involved in promoting more production of the water pump Aqaporin 4 channels in neural stem cells within the subependymal zone. (24) The subependymal zone is in the lateral part of the lateral ventricle which is a cerebrospinal fluid filled area near the center of the brain, (27), which is involved in fluid balance and drainage of the glymphatic system. (25) GABA receptors are also involved with flow of chloride ions across membranes (for an inhibitory effect on nerve signaling, (pp 126-131, 1), and affect fluid balance in areas of the brain without the blood brain barrier which makes diffusion of water across the brain membranes more possible. (26)

Alcohol also inhibits the action of the excitatory neurotransmitter glutamate, particularly at the NMDA receptor, (23), which is an excitatory ion channel and also allows calcium to enter the cell where the mineral can activate many functions within the cell. (pp 120-126, 1) If drinking alcohol is not preferred or legal due to age or advised due to pregnancy or possibility of becoming pregnant then GABA (gamma-aminobutyric acid) is available as an over the counter supplement, typically in a form that melts in the mouth to promote more direct absorption. While it is not typically referred to as an amino acid due to its role as a neurotransmitter, it is simply an amino acid, a smaller molecule from which proteins can be formed. The level of GABA a has been found to be reduced in the brains of patients with severe Alzheimer’s Disease and its use as a treatment has been studied, (29), levels in other abnormal brain cells were found to be elevated in a specific area of the brain of patients with Alzheimer’s Disease and treatment to increase transport of GABA has also been studied. (30)

Or sleep, in the form of a short nap, may also help promote GABA. Naps may benefit our health in part because of a beneficial effect on GABA promotion by increased glymphatic action in the brain – twenty minutes of sleep may be adequate. (28)

An overview of the glymphatic system and lifestyle and dietary tactics that might improve its function are described in a video by a nutritionist: (21); and also in a self-help style article by a different person: (22).

Some types of magnesium supplements including magnesium threonate may also help. Magnesium within the brain has many functions including inhibiting the NMDA glutamate receptor which would prevent excess calcium from entering the cell. (pp 120-126, 1)

We tend to hear about neurotransmitters such as serotonin for depression or dopamine and Parkinson’s disease, yet we rarely hear that calcium is the mineral that signals the release of both of those and over one hundred other neurotransmitters that are involved in nerve signals within the brain or throughout the body (page 85, 1.Neuroscience, 6th Ed.). Neurotransmitters include excitatory and inhibitory chemicals and they activate or inhibit the firing of a nerve signal. GABA can be a calming/inhibitory neurotransmitter that may be low when anxiety is a problem. Magnesium is the mineral inside cells which helps control how much calcium will be allowed to enter. Excess calcium can cause excess release of neurotransmitters. Magnesium deficiency can also be involved when anxiety is a symptom.

Adequate fluid is also likely important for adequate cleansing of waste from the brain by the glymphatic system. Problems with edema/swelling in other areas of the body or problems with hypertension may indicate problems with the lymphatic system in general. Moderate exercise helps the muscle power of movement also move extracellular fluid and lymphatic fluid through the lymphatic vessels to lymph nodes to be filtered by blood cells. Waste is removed into blood vessels for later excretion by the kidneys.

Additional note – adenosine was mentioned in the series on demyelination as a chemical that may lead to more breakdown of cells or myelin. It is produced as a metabolite of normal energy production and increased levels seem to be involved in our beginning to feel sleepy, signaling a need for rest – which would then give the brain clean up glymphatic system a chance to work on decreasing levels — so feeling sleepy? Your brain may be trying to tell you it is time to clean up after a strenuous workout whether physical or mental.  (See the What Makes You Sleep? section in the NHLBI article about Sleep Deprivation and Deficiency)

For more general information about promoting sleep and coping with insomnia see the post “Sleep and Health.”

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326841/Reference: pp 85-112, “Synaptic Transmission,” Neuroscience, 6th Edition, Editors D. Purves, G.J. Augustine, D. Fitzpatrick, W.C. Hall, A.S. LaMantia, R.D. Mooney, ML. Platt, L.E. White, (Sinauer Associates, Oxford University Press, 2018, New York) (Barnes&Noble)
  2. Glymphatic System May Play Key Role in Removing Brain Waste, Neurology Reviews, 2016 October;24(10):13   https://www.mdedge.com/neurologyreviews/article/114150/alzheimers-cognition/glymphatic-system-may-play-key-role-removing
  3. Understanding the Glymphatic System, Neuronline, adapted from the SfN Short Course The Glymphatic System by Nadia Aalling, MSc, Anne Sofie Finmann Munk, BSc, Iben Lundgaard, PhD, and Maiken Nedergaard, MD, DMSc http://neuronline.sfn.org/Articles/Scientific-Research/2018/Understanding-the-Glymphatic-System
  4. Tsutomu Nakada, Ingrid L. Kwee, Fluid Dynamics Inside the Brain Barrier: Current Concept of Interstitial Flow, Glymphatic Flow, and Cerebrospinal Fluid Circulation in the Brain. The Neuroscientist, May 24, 2018, http://journals.sagepub.com/doi/10.1177/1073858418775027#articleCitationDownloadContainer
  5. Bruce Goldman, The beating brain: A video captures the organ’s rhythmic pulsations. Scope, Stanford Medicine, July 5, 2018, https://scopeblog.stanford.edu/2018/07/05/the-beating-brain-a-video-captures-the-organs-rhythmic-pulsations/?linkId=53912604
  6. Geir Ringstad, Lars M. Valnes, Anders M. Dale, et al., Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. JCI Insight. 2018;3(13):e121537 https://insight.jci.org/articles/view/121537?utm_content=buffer13f62&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer
  7. Brain discovery could block aging’s terrible toll on the mind. University of Virginia Health System, EurekAlert! Science News, July 25, 2018, https://www.eurekalert.org/pub_releases/2018-07/uovh-bdc072518.php
  8. Da Mesquita S., Louveau A., Vaccari A., et al., Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease, Nature, 185,191, Vol 560, Issue 7717, 2018/08/01. https://www.nature.com/articles/s41586-018-0368-8
  9. Albargothy N. J., Johnston D. A., MacGregor‑Sharp M., Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. Acta Neuropathologica (2018) 136:139–152 https://link.springer.com/epdf/10.1007/s00401-018-1862-7?shared_access_token=oYhOYaeYOAlkFhECIjAc6Pe4RwlQNchNByi7wbcMAY7lrBk-VqU01OilsaKMVR9FXaHRKmFQ1tkD03g-Q04DmsYSxRC_gucPZRYlFW0xfyU2pYNfhmwcokVbMCreuzU3wBLsjKpRasKo-6HXTJLMHNXMqFbaSsQVIB34EgzIUsc%3D
  10. Tamara Bhandari, Lack of Sleep Boosts Levels of Alzheimer’s Proteins, The Source, Washington University in St. Louis, Dec. 27, 2017, https://source.wustl.edu/2017/12/lack-sleep-boosts-levels-alzheimers-proteins/
  11. Yo-El S Ju, Sharon J Ooms, Courtney Sutphen, et al., Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain, Vol 140, Issue 8, 1 August 2017, Pages 2104–2111, Oxford Academic, https://academic.oup.com/brain/article/140/8/2104/3933862
  12. Krista Burns, American Posture Institute: Proper Sleeping Posture for ‘Brain Drain,’ April 5, 2017, https://americanpostureinstitute.com/proper-sleeping-posture-for-brain-drain/
  13. Patricia Farrell, Sleep: Everyone Needs It and So Do You, March 16, 2017, https://www.amazon.com/dp/152061294X
  14. Melanie D. Sweeney, Berislav V. Zlokovic, A lymphatic waste-disposal system implicated in Alzheimer’s disease. July 25, 2018, https://www.nature.com/articles/d41586-018-05763-0?utm_source=twt_na&utm_medium=social&utm_campaign=NNPnature
  15. Nadia Aalling Jessen, Anne Sofie Finmann Munk, Iben Lundgaard, Maiken Nedergaard, The Glymphatic System – A Beginners Guide, Neurochem Res. 2015 Dec; 40(12): 2583–2599. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/
  16. Maiken Nedergaard, Steven A. Goldman, Brain Drain, Sci Am. 2016 Mar; 314(3): 44–49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347443/
  17. Rainey-Smith S. R., Mazzucchelli G. N., Villimagne V. L., et al. Genetic Variation in Aquaporin-4 Moderates the Relationship Between Sleep and Brain Aβ-amyloid burden. Translational  Psychiatry, (2018) 8:47 https://www.nature.com/articles/s41398-018-0094-x.epdf?author_access_token=iK09AkugOzYXUjXJCpGfIdRgN0jAjWel9jnR3ZoTv0P4SU0l7P8A1C64dg2xJ-HX7jlpuvyMeHzBYm6I5D0yMRBsx023MtG5Y3KNpj4EoNEqA4ELFuByqeysfTCRKZdGegxohMN9WLBb_S6H0UZYpw%3D%3D
  18. Brown B., Rainey-Smith S. R., Dore V., et al., Self-Reported Physical Activity is Associated with Tau Burden Measured by Positron Emission Tomography. Journal of Alzheimer’s Disease, vol. 63, no. 4, pp. 1299-1305, May 30, 2018 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad170998
  19. Chloe Chaplain, Drinking wine every day could help prevent Alzheimer’s, experts say. London Evening Standard, June 6, 2018, https://www.standard.co.uk/news/health/drinking-wine-every-day-could-help-prevent-alzheimers-experts-say-a3856646.html
  20. In Wine, There’s Health: Low Levels of Alcohol Good for the Brain. Feb. 2, 2018, University of Rochester Medical Center, https://www.urmc.rochester.edu/news/story/5268/in-wine-theres-health-low-levels-of-alcohol-good-for-the-brain.aspx
  21. Brianna Diorio, Glymphatic System 101, video,August 8, 2018,  https://vimeo.com/283708099?ref=tw-share
  22. Sydney, How To Detox Your Brain By Hacking Your Glymphatic System. A Healthy Body, May 18, 2018, http://www.a-healthy-body.com/how-to-detox-your-brain-by-hacking-your-glymphatic-system/
  23. The Effects of Alcohol on the Brain, The Scripps Research Institute, https://www.scripps.edu/newsandviews/e_20020225/koob2.html
  24. Li Y, Schmidt-Edelkraut U, Poetz F, et al. γ-Aminobutyric A Receptor (GABAAR) Regulates Aquaporin 4 Expression in the Subependymal Zone: RELEVANCE TO NEURAL PRECURSORS AND WATER EXCHANGE. The Journal of Biological Chemistry. 2015;290(7):4343-4355. doi:10.1074/jbc.M114.618686. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326841/ (24)
  25. Plog BA, Nedergaard M. The glymphatic system in CNS health and disease: past, present and future. Annual review of pathology. 2018;13:379-394. doi:10.1146/annurev-pathol-051217-111018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803388/ (25)
  26. Cesetti Tiziana, Ciccolini Francesca, Li Yuting, GABA Not Only a Neurotransmitter: Osmotic Regulation by GABAAR Signaling. Frontiers in Cellular Neuroscience, Vol. 6, 2012, https://www.frontiersin.org/article/10.3389/fncel.2012.00003 DOI=10.3389/fncel.2012.00003 ISSN=1662-5102 (26)
  27. Kazanis I. The subependymal zone neurogenic niche: a beating heart in the centre of the brain: How plastic is adult neurogenesis? Opportunities for therapy and questions to be addressed. Brain. 2009;132(11):2909-2921. doi:10.1093/brain/awp237. (27)
  28. Robert I Henkin, Mona Abdelmeguid, Sleep, glymphatic activation and phantosmia inhibition. The FASEB Journal, Vol 31, No. 1_supplement, April 2017, https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.749.4  (28)
  29. Solas M, Puerta E, Ramirez MJ. Treatment Options in Alzheimer’s Disease: The GABA Story., Curr Pharm Des. 2015;21(34):4960-71. https://www.ncbi.nlm.nih.gov/pubmed/26365140 (29)
  30. Zheng Wu, Ziyuan Guo, Marla Gearing, Gong Chen, Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model. Nature Communications, 5,  Article number: 4159 (2014) https://www.nature.com/articles/ncomms5159 (30)

Pomegranate extract update – has similar mechanism to NSAIDs

Update, 8/18/2018, for anyone interested in phytonutrient biochemistry or herbal medicinal foods: Wintergreen and wintergreen berries are also a natural source of a painkiller in the NSAID group – aspirin. The plant can also be a source of phytonutrients that activate TRPA1 channels which can affect fluid balance and other symptoms. Winterberries are in the cranberry family and have a minty flavor. They are in season currently and eating more of them seems to increase my symptoms of inflammation and swelling more than the pomegranate extract or pomegranate seeds. Having too many variables in an experiment makes it unclear which factor might be a cause or if both may be involved. Experimental method tries to narrow variables to one factor at a time. Stopping both pomegranate products and wintergreen berries helped but other symptoms got worse, adding pomegranate back to my diet didn’t make the inflammation/swelling symptoms much different but more recently adding the wintergreen berries back into my diet did make the symptoms of lower leg inflammation/swelling and pain worse.

An excerpt from one of my other websites, G3.6.1.5: People with overactive TRPA1 channels may be sensitive to:

  • “(Winter-green),” (G3.67); Wintergreen is a natural flavoring herb in the mint family. It is typically used as an essential oil as a flavoring in many foods and other types of products. It has medicinal benefits related to it containing the chemical that acts as the pain killing ingredient of aspirin.(G3.73) (effectivecare.info, G3)

My ongoing self study of pomegranate extract for my mental and physical health symptoms has led me to use a fairly small dose, daily though is still best. Missing even a few days seems to increase mood and anxiety problems but using a very large serving has some side effects. Lower leg and foot swelling is associated with some physical health problems but it can also be a side effect of NSAIDs pain killers such as ibuprofen. (7) Pomegranate extract has been shown to reduce pain and inflammation by the same mechanism as NSAIDS – inhibition of cyclooxygenase enzymes (COX1 and COX2,  with more inhibition of COX2 than COX1). It also may have an anti-inflammatory effect by reducing inflammatory cytokines that signal increase in production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2). (1) Prostaglandin E2 is made from arachidonic acid and is involved in the inflammation associated with rheumatoid arthritis and osteoarthritis. (2) Nitric oxide can be beneficial but it can also transform into reactive oxidative species and add to the antioxidant burden of metabolism. (5) (9) Other studies including an animal study on obesity found pomegranate extract reduced inflammatory biomarkers and increased nitric oxide, which might make it helpful for Metabolic Syndrome. (6)

Pomegranate extract was found helpful in a dose related level against mammary tumerogenesis in an animal study, (0.2-5 gram/Kg body weight was used). Reducing COX2, heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) pathways, and increasing Nrf2 pathways were found to be part of the mechanism for benefit. (4) That amount could be quite a lot. Equivalent amounts for a 75 kilogram/165 pound human would be 15-375 grams per day or roughly one tablespoon (15 grams approximately)-13.4 ounces/27 tablespoons per day. (Mammary tumerogenesis means the initial onset of breast cancer tumors.)

It helps to prop my feet when sitting or even lay down with my feet above my heart. I’m getting better at typing while laying down. Better mood and having feeling in my fingertips is worth it. There may some other health or diet issues affecting the leg swelling. Heart or kidney or vein problems can be a cause. (7) I do have vein problems and may have heart issues, which can be an increased risk with hyperthyroidism. Cutting back on salt, daily exercise, and elevating the lower legs above the level of the heart several times per day for a half an hour is recommended, wearing compression socks is also a recommendation and that makes me feel old. (7) Maybe 52 is old.

Lymphedema – lower leg swelling due to reduced drainage from vein problems may be the best fit for my personal history, and lack of stretching exercises lately may be part of the reason the problem has become worse lately. Physical therapists explain the problem and provide exercise, massage and compression wrapping suggestions in a free video available online. (8) The exercise routine is similar to what I generally do when I do stretching exercises – so that seems like a good habit to return to my daily schedule.

Lower leg swelling has been a symptom for me at various stages of previous ill health and with some other medications I’ve used in the past, but currently it does seem worse when I use larger amounts of the pomegranate extract. One teaspoon a day helps with the stable mood and I haven’t had numbness in my fingertips in months with the ongoing daily use of pomegranate extract in larger amounts, 2-3 tablespoons was typical. I stopped use of it altogether when the leg swelling became a problem to see if the swelling would get better but the mood symptoms got worse again after having seemed fine for quite a while – quite a while while using pomegranate extract daily and the leg swelling didn’t get a lot better. Being not well is unpleasant and some side effects can be better than being unwell.

Breast cancer treatments currently may cause hair loss, severe vomiting and may leave the patient with cognitive decline afterwards, and pomegranate extract doesn’t cause any of those symptoms in the amounts that I’ve tried. It is a diuretic and causes increased urination which I cope with by drinking extra fluids and using the pomegranate extract early in the day rather than at night. I may be preventing breast cancer tumor development (4) while drinking extra fluid and urinating in increased amounts – getting old isn’t great but the alternative isn’t better. I may go buy my first pair of compression socks and feel young at heart if not in body.

Industry math – one pomegranate peel makes about six cups of extract by my method which would provide 288 teaspoons/96 tablespoons. It may have improved somewhat but the worsening in mood was more obvious.  From an industry perspective getting 288 servings of a mood and nerve treatment from one pomegranate peel seems like it could be profitable. Dehydrating one teaspoon into a capsule serving also seems possible. Side effects with psychiatric medications are unfortunately common and can include swelling/edema of the lower legs or more severe edema including facial edema.

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./  

  1. Shukla, Meenakshi & Gupta, Kalpana & Rasheed, Zafar & A Khan, Khursheed & Haqqi, Tariq. (2008). Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX-II activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes in vitro. Journal of inflammation (London, England). 5. 9. 10.1186/1476-9255-5-9.
  2. Jean Y. Park, Michael H. Pillinger, Steven B. Abramson, Prostaglandin E2 synthesis and secretion: The role of PGE2 synthases, Clinical Immunology, Vol 119, Iss 3, 2006, pp 229-240, ISSN 1521-6616, https://doi.org/10.1016/j.clim.2006.01.016.
    https://www.sciencedirect.com/science/article/pii/S1521661606000453 (2)
  3. Arachidonic Acid – an overview, ScienceDirect, https://www.sciencedirect.com/topics/neuroscience/arachidonic-acid (3)
  4. Mandal A, Bhatia D, Bishayee A. Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling PathwaysNutrients. 2017;9(5):436. doi:10.3390/nu9050436. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452166/ (4) From Abstract: “Mammary tumor samples were harvested from our previous chemopreventive study in which PE (0.2–5.0 g/kg) was found to reduce mammary tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF-κB, inhibitory κBα (IκBα) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IκBα, hindered the translocation of NF-κB from cytosol to nucleus and increased the expression and nuclear translocation of Nrf2 during DMBA-induced mammary tumorigenesis.” From Introduction:”During the last decade, pomegranate fruit has been gaining a widespread reputation as a dietary supplement as well as a functional food due to emerging scientific evidence on potential health benefits, including prevention and/or treatment of cardiovascular ailments, neurological disorders, oncologic diseases, dental problems, inflammation, ulcer, arthritis, microbial infection, obesity, diabetes, acquired immune deficiency syndrome and erectile dysfunction [,,,,,]. Pomegranate fruit contains phytochemicals, including flavonoids (e.g., anthocyanins and catechins), flavonols (e.g., kaempferol and quercetin), flavones (e.g., apigenin and luteolin), conjugated fatty acids, hydrolyzable tannins and related compounds which are thought to be responsible for various biological and pharmacological activities [,,,,,]. Based on preclinical and clinical studies conducted by various laboratories worldwide, pomegranate-derived substances, such as juice, extracts and phytoconstituents exhibited cancer preventive and therapeutic effects against colon, liver, lung, prostate and skin cancer [,,,,]. Various extracts, fractions and phytochemicals from pomegranate fruit, peel, seed and flower demonstrated cytotoxic, antiproliferative, proapoptotic, antiangiogenic, anti-invasive, and antimetastatic properties against estrogen receptor-positive and ‑negative breast cancer cells [,,,,,,,,,,,,,]” (4)
  5. Matsubara K, Higaki T, Matsubara Y, Nawa A. Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia. Miller FJ, ed. International Journal of Molecular Sciences. 2015;16(3):4600-4614. doi:10.3390/ijms16034600. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394437/ (5)
  6. Filomena de Nigris, Maria Luisa Balestrieri, Sharon Williams-Ignarro, Francesco P. D’Armiento, Carmela Fiorito, Louis J. Ignarro, Claudio Napoli,
    The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats, Nitric Oxide, Volume 17, Issue 1, 2007, pp 50-54, ISSN 1089-8603, https://doi.org/10.1016/j.niox.2007.04.005.
    (http://www.sciencedirect.com/science/article/pii/S1089860307000432) (6)
  7. Swollen Legs: Causes and Treatments, WebMD, https://www.webmd.com/dvt/why-legs-puffy#1 (7)
  8. Bob Schrupp, Brad Heineck, 10 Exercises for Leg Lymphedema (Swelling or Edema of the Lower Extremities). physicaltherapyvideo, https://www.youtube.com/watch?v=3t8Kp99e50k&feature=youtu.be (8)

  9. Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative Stress in Preeclampsia and Placental Diseases. International Journal of Molecular Sciences. 2018;19(5):1496. doi:10.3390/ijms19051496.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983711/ (9)

Translational Research – translating research into patient care strategies

“The answer is 17 years, what is the question: understanding time lags in translational research” – Morris, et al, 2011 (1)

It takes far too long for research findings to be ‘translated’ into health messages or techniques that reach the patient in need of health care guidance – 17 years on average according to the review of research study by Morris et al (2011). The team’s conclusion is that translational research is in need of further study but with more well defined terms and types of measurements so research by different teams can be compared. Twenty three studies were reviewed but the research parameters were diverse and not readily comparable. (1)

As a person with training and experience as a health care professional I followed general recommendations for general health and weight loss for many years but they didn’t help and I kept getting more sick with problems that didn’t show up on lab tests. Being told regularly that my symptoms must therefore be psychosomatic (mentally based) and that I should see a talk therapist did lead me to spending time with talk therapists and it helped somewhat but I kept getting more sick.

I knew I was physically sick, not just mentally making myself sick from stress or anxiety because I wasn’t always stressed or anxious and had always had some minor but chronic health problems as a child. So I eventually gave up on the standard not-helping-much answers and instead paid closer attention to my daily routine and dietary choices and slowly stopped doing any of the things that seemed to make me feel worse the next day. With the pay attention method I got somewhat better. Fibromyalgia and chronic fatigue symptoms were improved. Iodine supplements helped me with weight loss and a low dose antibiotic protocol developed for an autoimmune type of condition helped relieve my severe migraine problem.

Prescriptions can be quick and easy answers but they don’t always work, sometimes makes things worse, can delay trying other strategies that might work better – and can be expensive in insurance co-pays or be an out of pocket self pay expense. Health needs adequate sleep, with black out curtains and no lights, not even a digital alarm clock – keep it in a bedside table drawer or cover it with a towel. Even a little light at night can interfere with our production of melatonin and it helps with a variety of health needs throughout the body.

Health requires regular stretching and exercise that works out the heart and lungs and builds the other muscles somewhat. To maintain bone density requires weight bearing exercise – lifting weights in a warehouse or digging in a garden or in a gymnasium. Having the freedom to read text documents on your laptop while standing and using hand weights can multitask physical fitness needs with work or school needs. Varying positions and going for short walks occasionally is healthier than any type of job that requires too much of the same motions or having to stay in the same position for long periods of time.

Standing desks that can easily transition to a sitting desk can be as simple as a couple boxes under your laptop. Standing can allow some leg and arm stretches and then the boxes can be removed for some time spent sitting to type more intensively. Eight full hours in either position might be more of a health risk than being able to switch between the two options. (2)

Health requires all of the nutrients and additional fiber and antioxidants and other phytonutrients that aren’t considered essential in the same way vitamins are but may be necessary for more optimal health.

If it is reasonable to want to prevent measles or chickenpox, or other infectious diseases, then it seems reasonable to want to prevent age related degenerative disease by providing the body more of what it needs to remove toxins and rebuild tissue as it wears out. Even brain cells are replaced with new ones  – our entire body is not the same body that we had as a newborn. We are regularly removing old cells and growing new ones.

All truths are easy to understand once they are discovered. The point is to discover them. ~ Galileo

And the point of translational research is to improve the process of translating research findings into effective strategies for patient care. If research is still in early stages it may not be safe for all patients, finding out how to identify which patients it might help would then be a necessary step before translating the findings into patient education messages or health care protocols. How to guides ideally will always include safety warnings about which patients the health messages might harm if they were to use or be ineffective for their use.

As an individual it is good to know your rights as a patient and to seek health care professionals that take the time to listen. As a patient seeking a second opinion may be helpful and it can be helpful to write down your symptoms and mood changes, your daily diet or sleep habits, and any other routine habits in order to look back occasionally to see if any patterns show up in what is helping or not helping you feel better. We all need to remember that we are the ones living our lives and that makes us the ones in charge of taking care of our own health as best as we can.

It can take three weeks or more to build a habit and that suggests the reverse is likely true – and keeping a written tally sheet about the habit you want to change can help stay on track and help show where you may be veering off track. For more guidance, see Changing Habits, The Learning Center, University of North Carolina. (3)

Your Health Insurance agent is not your mother (probably), and in the current system large bills can lead to more profit for health insurance companies – so watch out for your  own budget by taking care of exercise, diet, and sleep habits and send your Health Insurance agent a nice card at the holidays instead of having them on speed dial for questions about your enormous co-pays. Insurance is nice but 10 or 20% of an enormous bill is still more than most of us have in the bank or can easily borrow. (4)

Bankruptcy due to health care costs has become too common – stay out of bankruptcy court by spending more time on daily health care habits – the research is fairly conclusive regarding the basics –

  • ideally at least 30-60 minutes of exercise 3-5 times per week,
  • drink plenty of water for thirst
  • and eat 5-9 servings of vegetables/whole fruit per day, get adequate protein, whole grains and essential omega 3 fatty acids without too much saturated and trans fats each day. Trying to include a serving of fatty fish three times per week can be a source of omega 3 fatty acids or vegetarian sources include walnuts, hemp seed kernels or ground flax seeds. Including a serving of beans, nuts and seeds on most days may increase the amount of magnesium and other important trace nutrients in the daily/weekly diet.
  • Six hours of sleep seems to be a minimum need for most people and more than eight hours on a regular basis may be too much or a sign of health or depression problems in adults once they are out of the teen years, (teens may benefit from ten hours of sleep per day, (6)). Short naps during the day can be a healthful activity and may increase work productivity, 20-30 minutes may be ideal. Longer naps may lead to waking up groggy instead of refreshed. (5)
  • Social activity and other relaxing hobbies also seem to be helpful for health.

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes. Thanks./

  1. Zoë Slote Morris, Steven Wooding, and Jonathan Grant,

    The answer is 17 years, what is the question: understanding time lags in translational research., J R Soc Med. 2011 Dec; 104(12): 510–520. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241518/

  2. Robert H. Shmerling, MD, The Truth Behind Standing Desks, Sept. 23, 2016, Harvard Health Blog, Harvard Health Publishing, health.harvard.edu,  https://www.health.harvard.edu/blog/the-truth-behind-standing-desks-2016092310264?utm_campaign=shareaholic&utm_medium=twitter&utm_source=socialnetwork
  3. Changing Habits, The Learning Center, University of North Carolina, https://learningcenter.unc.edu/tips-and-tools/changing-habits/
  4. Why Your Health Insurer Doesn’t Care About Your Big Bills, propublica.org, https://www.propublica.org/article/why-your-health-insurer-does-not-care-about-your-big-bills
  5. Napping, sleepfoundation.org, https://sleepfoundation.org/sleep-topics/napping
  6. See Chapter Two: The Lost Hour, Po Bronson and Ashley Merryman, NurtureShock: New Thinking About Children, Twelve, Hatchette Book Group, New York, 2009 http://www.nurtureshock.com/

Additional references for more information on translational medicine:

Excerpt from a post about my own genetic screening (Genetic Screening can give guidance about potential medication adverse reactions, 2018):

Additional reference for further discussion of the advances in the use of genetic screenings for medication risk is available in a book that is already slightly dated with the rapid advances in technology but as a starting point it is helpful for an overview on the history of technological advances in the area of medical care: The Creative Destruction of Medicine: How the Digital Revolution will Create Better Health Care, by Eric Topol, M.D., 2013. Basic Books. ISBN: 978-0465061839. (1) (“Book Review…,” and summary, by Jung A Kim, RN, PhD, PubMed_2)

One of the pioneers in personal genetic screening was Esther Dyson, a venture capitalist. She quoted a colleague regarding why she agreed to be one of the first ten participants in the Personal Genome Project:

“You would no more take a drug without knowing the relevant data from your genome than you would get a blood transfusion without knowing your blood type.” [128] (1)

The future of individualized health care will include genetic screening for everyone and what isn’t addressed in the book by cardiologist and translational research specialist Eric Topol, M.D. is the use of genetic screening for individualized nutrition guidance. In addition to discovering what medications may work better or be more dangerous for an individual genetic screening can target which types of exercise or diet plans may be more or less beneficial and which nutrients may need to be restricted or supplemented more than the average guidance.

My previous genetic screening was for fewer genes but which were chosen as most commonly a problem for children on the autism spectrum – I had 11 of the 30 and the guidance led to supplements and diet changes that have helped me feel better and have better mood stability – Methylation Cycle Defects – in me, Genetic Screening “For Research Purposes Only” – at this stage “For Research Purposes Only” is a legal phrase as genetic screening is not considered consistent enough for use as a diagnostic tool, but my personal health is of significant interest to me.

  1. Eric Topol, M.D,, The Creative Destruction of Medicine: How the Digital Revolution will Create Better Health Care, 2013. Basic Books. ISBN: 978-0465061839.  (1) Chapter 5, Biology: Sequencing the Genome, page 117: [128]
  2. Jung A Kim, RN, PhD, Book Review: The Creative Destruction of Medicine: How the Digital Revolution will Create Better Health CareHealth Inform Res. 2013 Sep; 19(3): 229–231.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810531/ PubMed_2)

[128] Esther Dyson, “Full Disclosure,” Wall Street Journal, July 25, 2007, A15.