Tag: cannabinoids

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Good news/Bad news about Multiple sclerosis research

The good news about Multiple sclerosis (MS) research is that there seems to have been a major breakthrough in treatment, the bad news is that research regarding demyelinating disorders which includes MS seems to have slowed down (1) – finding a solution, a medical answer, that isn’t politically approved of or one that is able to be easily patent protected may be the reason for the bad news. Finding an answer that you don’t like shouldn’t mean we stop asking the question. Work is progressing on genetic modification of mitochondrial DNA differences that can cause demyelination disorders and success has been seen in animal models for disease. Aging increases the risk for different types of mitochondrial DNA changes that can cause a variety of symptoms and diseases. (mitoTALENS/session by Moraes/28)

(Ubiquitin (a protein, not the same as CoQ10/ubiquinone, an electron carrying quinone involved in energy metabolism, 29) is needed for identifying which mitochondria are damaged and need to be recycled in the normal way, by autophagy/mitophagy, which involves the debris being taken into a container particle called lysosomes – imagine a cellular vacuum cleaner that can then recycle any useful material and discard any non-useful, potentially toxic material. See the session on Mitochondria in Parkinson’s Disease/Youle: 28)

Cannabinoids seem to be the good news treatment for MS in humans, whether as purified extracts of medical marijuana or as the whole product which can contain many cannabinoids and medically active terpenes.  An overview published in 2016 regarding the role of cannabinoids in neurology in various types of autoimmune disease: (2). An overview of the role of cannabinoids in neuroinflammatory conditions published in 2008: (3). An opinion article published in 2018 regarding the potential role of cannabidiol ( a non-euphoric cannabinoid) to improve mobility for patients with Multiple sclerosis: (4).

What is Multiple sclerosis?

Multiple sclerosis is a chronic condition that seems to be autoimmune in nature where the body is breaking down the protective coating around the branching segments between nerves. The coating is called the myelin sheath and it acts a little like the plastic coating around an extension cord. Myelin on a nerve fiber or plastic on an extension cord keeps the electrical signals on the inside and out of danger of creating sparks elsewhere along the path of the cord or nerve fiber.

What are cannabinoids?

Cannabinoids are directly involved in making strong and flexible cell membranes as they are building blocks that make up portions of the membrane, like bricks in a wall. They can also be signaling chemicals that can be activated when released from the membrane. Excess calcium inside of a cell can be a signal that causes the release of cannabinoids. Once they are released they break down into their two basic components, phospholipids and a free fatty acid, often arachidonic acid. The problem is two part – 1) both of the components of cannabinoids once they are released from the membrane can become signaling chemicals that can lead to increased inflammation, NSAID pain killers (aspirin, naproxen, ibuprofen helped reduce level of fatigue experienced by MS patients) may help block the negative effects of excess free arachidonic acid (21); 2) if too many bricks are released from the wall, then the wall may no longer function – the plastic coating on the extension cord may allow sparks through that can be a risk for an electrical fire. In the case of Multiple sclerosis the nerve damage and lack of myelin sheathing around nerve fibers causes difficulties with muscle control and the patient may have increasing difficulty walking and doing other normal daily tasks.

Preventing the increased release of cannabinoids from the membrane walls would likely to the best plan for preventing the resulting increase in inflammatory signaling chemicals they form and the reduction in membrane function. The amount of cannabinoids present can cause opposite effects, small or medium amounts can have beneficial effects while large amounts may have significantly different effects. Mitochondria are the main energy production center of the cell, where sugar is turned into a usable form of energy with the chemical shorthand name ATP or ADP. Both are phosphochemicals differing in the number of phosphate groups, adenosine tri-phosphate and adenosine di-phosphate. The amount of calcium within the cell and within the mitochondria may be different and cannabinoid can affect the movement across the mitochondrial membrane and cause differenct effects depending on the amount of calcium in each area and the amount of cannabinoids that are present. It’s complicated is the short story. This article goes into a longer  but still simplified description of the chemistry. (23)

And part of the point is that having adequate cannabinoids and adequate phosphonutrients and adequate but not excessive calcium are all important for cellular health and the ability to produce energy – and to not be fatigued – excessively tired all of the time. And in order to have adequate calcium but not excessive the cells need adequate magnesium and adequate protein and phosphonutrients in order to hold it ready for use – like taxicabs circling the block ready to discharge magnesium as a free ion when and where it is needed. The topic of magnesium, and the need for protein and phosphonutrients was introduced in a recent post. Magnesium blocks entry of excess calcium from being able to enter the interior of the cell, where it can cause increased release of cannabinoids from their storage positions within the cell membranes. Ibuprofen, but not other NSAIDs such as naproxen, also help reduce the amount of breakdown of cannabinoids. (pp 82-83, 24)

What are oligodendrocytes?

A type of specialized brain cell called oligodendrocytes are responsible for building or repairing the myelin sheath. Multiple sclerosis involves increased loss of oligodendrocytes. The specialized cells have calcium permeable glutamate receptors and are more susceptible to oxidative stress than average cells so they are particularly at risk for being damaged by ongoing emotional or physical stress or a traumatic brain injury. (6) Sphingomyelin is one of the building blocks of the myelin sheath, (7),  and is formed by oligodendrocytes. (8)

The body is complicated and needs many/all of the nutrients for optimal health. More nutrients and other lifestyle issues that may benefit myelin production or increase risk are discussed in a list of tips for regenerating myelin, phosphatidylserine, a phospholipid, is one of the recommendations; other conditions that may include myelin breakdown besides Multiple sclerosis are also mentioned: (22). 

Problems with vitamin D availability may also be involved in the body being more prone to autoimmune reactions by the immune system (attack on our own healthy cells instead of only attacking foreign or damaged cells); and on the natural building or repair of the myelin sheath. (5) And just to keep things interesting – iron is important but too much within the oligodendrocytes may increase risk for MS; polyunsaturated fats are also important but their reactivity may increase risk to the oligodendrocytes from oxidative stress; lack of Nrf2 may be involved in the susceptibility to oxidative stress in the development of MS due to damage to the oligodendrocytes; and the oligodendrocytes have an abundance of calcium permeable glutamate receptors so excess glutamate may increase risk of excess calcium entry into the cells which can lead to cell death. (8)

Summary points for protecting oligodendrocytes –

  • all nutrients are important, (22), but balance is also important.
  • Avoid excess emotional and physical stress if possible.
  • Adequate iron is important because the oligodendrocytes need more than average in order to be able to make the myelin sheath. Some patients may have an underlying genetic difference that leads to their needing supplementation of a well absorbed form of iron throughout their life. Genetic screening and individualized metabolic guidance may be needed for optimal treatment of patients with MS as it may have differing causes. A true autoimmune antibody/antigen has not been identified. (10)
  • In general however, avoid excess iron (fortified breakfast cereals and meats for example; men and menopausal women who eat large servings of very iron-fortified foods or large servings of iron rich meats can be more at risk for iron overload. Donating blood occasionally can benefit society and may help protect against the risk of iron overload for people who do not menstruate. Food sources of iron and more information about donating blood: (9) Iron overload can be a cancer risk and tends to be more common than iron deficiency in the non-menstruating population.(11))
  • and avoid excess free glutamate (frequently used in seasonings and naturally found in fermented products such as soy sauce. It is in many processed foods, (12)).
  • Eat a balance of omega 3, (22), and omega 6 polyunsaturated fatty acids.
  • Eat plenty of antioxidant rich foods regularly that also include Nrf2 promoting phytonutrients and other phospholipid containing nutrients. Here is some Nrf2 promoting foods and menu ideas: G10: Nrf2 Promoting Foods.
  • And cannabinoids or other phospholipid/phosphonutrient containing foods include these, many of which are also Nrf2 promoting foods:

Food Sources of Phospholipids and other phospho-nutrients, a partial list:

Hemp seed kernels and oil; Artemisia turanica/wormwood leaf; amaranth seed; asparagus; avocado fruit or the inner kernel, dried and powdered; beans/legumes; cardamom seeds and powder; carrots; celery stalks and leaves; cocoa beans and cocoa powder, baker’s chocolate, dark chocolate and to a lesser amount milk chocolate and chocolate syrup; coconut; cumin seed/powder; fennel seed, flax seed, pine nuts; sesame seeds, pumpkin seed kernels, squash seeds; butternut squash and pumpkin; gingko leaf; grapefruit and orange juice with the pulp; Jerusalem artichoke (this is a root vegetable rather than a green artichoke); lettuce, spinach and mustard leaves and other leafy green vegetables and herbs; nuts/peanuts, cashews, walnuts; oats; okra seeds; onion root, leek leaves, garlic;  parsnip root; pomegranate seeds and pomegranate peel extract;rice, white or brown but the bran is the best source; rosemary; sorghum;  sweet potato or yam; buckwheat (a seed botanically that is not wheat and is gluten free); wheat. (G.26)

The current treatments for Multiple sclerosis are very costly, and may not help all patients while also tending to cause negative side effects.

Returning to the original question – why has the ratio of research being published about demyelinating disorders declined since 2013? It is possible that the answer might be that medical marijuana or a recommendation to eat more dark cocoa and beans, nuts, and seeds is not as profitable as the older MS treatments may average $60,000 per year and newer treatments cost 25-60% more than that, (13), which would be an average prescription cost of $75,000-96,000 per year per patient with Multiple sclerosis. Good quality cocoa is expensive but can fit within most grocery budgets. Being a medical marijuana patient might cost around $12,000 per year for a patient using it several times each day. Use of ibuprofen daily might cost a few hundred dollars per year depending on the amount used and whether it was a name brand or off brand. (21) (24) (Note – long term use of ibuprofen may cause intestinal problems, ginger (about 1/2 teaspoon) can be healing for the intestines and help with pain relief as well as ibuprofen and provided better pain relief when used in combination with ibuprofen in a study with arthritis patients. Ginger may be reducing inflammation by reducing the amount of cannabinoid breakdown to free arachidonic acids and preventing transformation into inflammatory eicosanoids. (27))

Efficacy and negative side effects are also worth considering – for that $60,000-96,000/year price tag only half of the patients may gain health benefits while many will experience negative side effects in addition to needing time and copays for office visits to receive some types of treatments. Fewer than half of patients receiving interferon-β treatment were found to benefit medically and many experienced side effects. (13)

The pharmaceutical industry frequently does medical research involving new drug treatments. The use of medical marijuana for the treatment of Multiple sclerosis or other demyelinating disorders is not legal at the Federal level as the herb is still scheduled as a substance with no medical benefit. Private research in states that have legalized medical use could possibly be performed however. Enrolling patients would likely need to be by self selection though, and for comparison purposes an experimental group of patients could be given a phospholipid rich diet plan to follow and a control group of patients receiving standard pharmaceutical treatments could also be followed to compare health outcomes with the current standard of care.

How many patients have Multiple sclerosis?

More math – there are about 400,000 people in the U.S. with Multiple sclerosis and about 10,000 newly diagnosed patients each year. (14) Averaging the cost of standard treatments to $78,000 per year would mean the 400,000 patients require $31,200,000,000 per year in pharmaceutical care. Thirty one billion dollars would buy a lot of cocoa. The number of patients living with the condition globally is estimated to be around 2.3 million people. (15) If they all received treatment at the average U.S. cost it would require $179.4 billion in care.

People living farther from the equator tend to have a greater risk for developing Multiple sclerosis so vitamin D deficiency may be involved.

Looking at the global distribution map on the link does visually suggest that vitamin D deficiency may be involved – it is not as much of a risk for nations around the equator where more sunshine would consistently be available.  Genetic differences may also be involved as it is more of a risk for Caucasians and people of central and northern European descent. It is rare for Inuits, Aborigines and Maoris. (14) (The Inuit native diet is rich in vitamin D from seafood sources.) A map of distribution risk across the U.S. also suggests a sunshine factor – rates below the 37th parallel are reduced compared to farther north. (15)

Sphingomyelin is found in the diet but needs to be made by the oligodendrocytes.

Why discuss eating cocoa or sources of phospholipids or vitamin D? Why not just eat sphingomyelin? We do eat some but our digestive systems break it down into smaller types of fats, (16), and then our oligodendrocytes have to rebuild it. Sphingomyelin tends to be found with cholesterol within the body, and both can affect the digestion of the other. (16)

Genetic differences may be involved in risk for MS. Variations in genes involved in Vitamin D metabolism may be a risk factor. There also may be differences in the cannabinoid metabolism involved or in other metabolic pathways.

Vitamin D can be made out of cholesterol when our skin is exposed to adequate sunshine. Genetic differences in vitamin D metabolism may be why some people are more prone to developing multiple sclerosis than others – speculatively. Genetic differences in vitamin D metabolism have been studied in relation with multiple sclerosis risk and a correlation was found however studies with supplementation have been inconclusive. (17) One nutrient solutions can not solve multiple nutrient problems – adequate iron but not too much, adequate balance of polyunsaturated fats to promote health without increasing inflammation, avoiding excess free dietary glutamate, and having adequate phospholipids and Nrf2 promoting foods in the diet may also all be important – in addition to having adequate vitamin D in the diet or from sunshine or tanning lights.

Vegetarian based diets include many foods that help reduce inflammation & protect against oxidative stress, & may save money.

Some more good news – a vegetarian based diet can provide many of those dietary factors and save money (about $750/year, (18)) compared to a meat based diet (which tends to be more inflammatory – i.e. oxidative stress promoting). More math – the economical vegetarian diet (2015 U.S. prices) was estimated to cost about $2,762/year which would add up to $6,353 million per year for the 2.3 million global population of people with MS instead of the $179.4 billion that would be needed for current pharmaceutical treatments for Multiple sclerosis. Phosholipid rich, Nrf2 promoting foods can also provide a good balance of omega 3 fatty acids and include sources of vitamin D and iron and tend to include many high quality vegetarian sources of protein such as nuts, beans, and seeds.

Cocoa has been found to reduce fatigue for MS patients and is a good source of phospholipids and Nrf2 promoting flavonoids.

Better news – cocoa, which is made from a bean that is rich in flavonoids, which are Nrf2 promoting phytonutrients, G10: Nrf2 Promoting Foods, and is a good source of phospholipids, (G.26), has been found to help reduce fatigue levels in patients with Multiple sclerosis while not increasing high blood sugar risk factors. (19)

Skip the sugar if possible, Insulin resistance may increase breakdown of the myelin sheath.

I add a spoonful of dark cocoa powder (unsweetened Baking cocoa) to my coffee – like mocha coffee without the syrup. Once you stop using sugar your taste buds adjust to not needing as much sweet taste – or add a little sugar or honey but artificial sweeteners may not be that helpful because the sweet taste is still signaling the body to increase insulin levels which then increases appetite and studies have found snacking calories are then increased -resulting in no overall reduction in calorie intake. Avoiding insulin resistance, frequently a problem with Type 2 Diabetes and Metabolic Syndrome, may also help protect against Multiple sclerosis risk as it may have something to do with the breakdown of the myelin sheath. (20)

/Disclosure: 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. James Lyons-Weiler, *A graph of all research studies regarding demylinating disorders such as Multiple sclerosis as a ratio of all medical research studies over time – there has been a significant decrease in the ratio since 2013. The graph begins with approximately 4/100,000 studies in 1944, peaks at approximately 46/100,000 in 1998/1999 and drops to approximately 7/100,000 in 2017/2018.   https://twitter.com/lifebiomedguru/status/1021794538682236929 (1)
  2. Katz D, Katz I, Shoenfeld Y,  Mini Review, Open Access, Cannabis and Autoimmunity – The Neurologic Perspective: A Brief Review. June 2, 2016, J Neurology, Neuromedicine. http://www.jneurology.com/articles/cannabis-and-autoimmunity–the-neurologic-perspective-a-brief-review.html (2)
  3. G. A. Cabral, L. Griffin-Thomas, Cannabinoids as Therapeutic Agents for Ablating Neuroinflammatory Disease. Endocr Metab Immune Disord Drug Targets. 2008 Sep; 8(3): 159–172.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750822/ (3)
  4. Thorston Rudroff, Jacob Sosnoff,Cannabidiol to Improve Mobility in People with Multiple Sclerosis. Opinion Article, Front. Neurol., 22 March 2018.   https://www.frontiersin.org/articles/10.3389/fneur.2018.00183/full (4)
  5. Cell-based study reveals that vitamin D can drive the activity of neural stem cells that promote myelin repair, MS Society of Canada, March 30, 2015, https://mssociety.ca/research-news/article/cell-based-study-reveals-that-vitamin-d-can-drive-the-activity-of-neural-stem-cells-that-promote-myelin-repair (5)
  6. Attila Köfalvi, Cannabinoids and the Brain, Springer Science & Business Media, Dec 22, 2007, pp 342 and 344, https://books.google.com/books?id=ZNIorLciZCoC&pg=PA342&lpg=PA342&dq=myelin+sheath+cannabinoid+metabolite&source=bl&ots=t0vcsRm2HK&sig=oDbCl2JBArCt9s5KT8xawwBrv5M&hl=en&sa=X&ved=0ahUKEwjf2MS3xbrcAhUBI6wKHdIEDbUQ6AEISDAE#v=onepage&q=myelin%20sheath%20cannabinoid%20metabolite&f=false (6)
  7. ElenaPosse de Chaves, Simonetta Sipione, Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction. Frontiers in Membrane Biochemistry, FEBS Letters, Vol 584, Issue 9, 3 May 2010, Pages 1748-1759, ScienceDirect,   https://www.sciencedirect.com/science/article/pii/S0014579309010564
    (7)
  8. Arundhati Jana, Kalipada Pahan, Sphingolipids in Multiple sclerosis, Neuromolecular Med. 2010 Dec; 12(4): 351–361.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987401/ (8)
  9. Iron-Rich Food-List of Meats, Vegetables and Meals, American Red Cross, https://www.redcrossblood.org/donate-blood/blood-donation-process/before-during-after/iron-blood-donation/iron-rich-foods.html (9)

  10. Susan J. van Rensburg,Maritha J. Kotze, Ronald van Toorn, The conundrum of iron in multiple sclerosis – time for an individualised approach. Metab Brain Dis. 2012 Sep; 27(3): 239–253.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402663/ (10)

  11. Iron: The Double-Edged Sword, The Physician’s Committee for Responsible Medicine, https://www.pcrm.org/health/cancer-resources/diet-cancer/nutrition/iron-the-double-edged-sword (11)
  12. Dr. Amy Yasko, Detecting Neuro-Provoking Foods, http://www.dramyyasko.com/wp-content/files_flutter/1279663001Neuroprovokers8.pdf (12)

  13. Daniel M. Hartung, PharmD, MPH, Dennis N. Bourdette, MD, Sharia M. Ahmed, MPH, Ruth H. Whitham, MD, The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: Too big to fail?,  Neurology. 2015 May 26; 84(21): 2185–2192. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451044/ (13)

  14. MS Statistics, multiplesclerosis.net, https://multiplesclerosis.net/what-is-ms/statistics/ (14)
  15. Multiple sclerosis: Facts, Statistics, and You, healthline.com, https://www.healthline.com/health/multiple-sclerosis/facts-statistics-infographic#2 (15)
  16. Åke Nilsson, Rui-Dong Duan, Absorption and Lipoprotein Transport of Sphingomyelin, January 2006, The Journal of Lipid Research, 47, 154-171, http://www.jlr.org/content/47/1/154.full (16)
  17. Shoemaker TJ, Mowry EM, A review of vitamin D supplementation as disease-modifying therapy. Multiple Sclerosis Journal, Volume: 24 issue: 1, page(s): 6-11 Jan 18, 2018, http://journals.sagepub.com/doi/full/10.1177/1352458517738131 (17)
  18. Justin Caba, A Vegetarian Diet Can Save You Around $750 Each Year When Compared To A Meat-Eating Diet. Oct. 9, 2015, MedicalDaily.com, https://www.medicaldaily.com/vegetarian-diet-can-save-you-around-750-each-year-when-compared-meat-eating-diet-356670 (18)
  19. S. Coe, E. Axelsson, V. Murphy, M. Santos, J. Collett, M. Clegg, H. Izadi, J.M. Harrison, E. Buckingham, H. Dawes, Flavonoid rich dark cocoa may improve fatigue in people with multiple sclerosis, yet has no effect on glycaemic response: An exploratory trial. Clinical Nutrition ESPEN, Oct. 2017, Volume 21, Pages 20–25   https://clinicalnutritionespen.com/article/S2405-4577(17)30280-2/abstract (19)
  20. Kristina Fiore, Does Insulin Resistance Degrade Myelin? – Imaging study suggests insulin resistance is linked to loss of myelin., Oct. 23, 2015, MedPageToday.com, https://www.medpagetoday.com/meetingcoverage/sfn/54260 (20)
  21. Sara Palumbo, Chapter 7 Pathogenesis and Progression of Multiple Sclerosis: The Role of Arachidonic Acid–Mediated Neuroinflammation. from the book edited by Zagon IS, McLaughlin PJ, editors. Multiple Sclerosis: Perspectives in Treatment and Pathogenesis [Internet]. Brisbane (AU): Codon Publications; 2017 Nov 27. https://www.ncbi.nlm.nih.gov/books/NBK470143/ (21)
  22. Jordan Fallis, 27 Proven Ways to Promote the Regeneration of Myelin. Feb. 18, 2017, Optimal Living Dynamics,  https://www.optimallivingdynamics.com/blog/25-proven-ways-to-promote-the-regeneration-of-myelin (22) 
  23. Adrian Devitt-Lee, CBD Science: How Cannabinoids Work at the Cellular Level to Keep You Healthy, Project CBD,  Dec. 15, 2016, alternet.org, https://www.alternet.org/drugs/cbd-science-mitochondria-mysteries-homeostasis-renewal-endocannabinoid-system (23)
  24. Editors, Emmanuel S. Onaivi, Takayuki Sugiura, Vincenzo Di Marzo, Endocannabinoids: The Brain and Body’s Marijuana and Beyond, (Taylor & Francis Group, 2006, Florida), pages 82 and 83 are from Chapter 3, by: E.S. Onaivi, H. Ishiguro, P. W. Zhang, Z. Lin, B. E. Akinshola, C. M. Leanoard, S. S. Chirwa, J. Gong, and G. R. Uhl, Chapter 3, Endocannabinoid Receptor Genetics and Marijuana Use. https://www.crcpress.com/Endocannabinoids-The-Brain-and-Bodys-Marijuana-and-Beyond/Onaivi-Sugiura-Di-Marzo/9780415300087 (24)
  25. J. Depew, RD, G10: Nrf2 Promoting Foods, 2018, effectivecare.info, G10: Nrf2 Promoting Foods. Particularly helpful for an overview of plant phytonutrients groups: Maria de Lourdes Reis Giada, Chapter 4: Food Phenolic Compounds: Main Classes, Sources and Their Antioxidant Power, Biochemistry, Genetics and Molecular Biology » “Oxidative Stress and Chronic Degenerative Diseases – A Role for Antioxidants”, book edited by José A. Morales-González, ISBN 978-953-51-1123-8, Published: May 22, 2013    https://www.intechopen.com/books/oxidative-stress-and-chronic-degenerative-diseases-a-role-for-antioxidants/food-phenolic-compounds-main-classes-sources-and-their-antioxidant-power (G10.11)
  26. Arlen Frank, Chemistry of Plant Phosphorus Compounds, Elsevier, Jun 3, 2013, https://books.google.com/books/about/Chemistry_of_Plant_Phosphorus_Compounds.html?id=6btpFSV1T2YC (G.26)
  27. Ginger Decreases Colon Inflammation, Prime Endoscopy Bristol, Oct. 12, 2011,  http://www.primeendoscopybristol.co.uk/ginger-decreases-colon-inflammation/ (27) 
  28. From Pediatric Encephalopathy to Alzheimer’s: Linking Mitochondria to Neurological Diseases. 2016 Neurobiology of Disease Workshops, Neuronline.sfn.org, http://neuronline.sfn.org/Articles/Scientific-Research/2017/From-Pediatric-Encephalopathy-to-Alzheimers (28)
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Cannabinoids and Alzheimer’s Disease

The body needs carbohydrates, proteins, fats, vitamins, trace minerals, and phospholipids and many other chemicals that can be made within the body if it is well-nourished and has average genetic and youthful abilities. That is a lot to expect from a body and a nutritionist can be a helpful expert to have on your team.

It is 420 day – a typical day in some circles to discuss or celebrate cannabinoids – so some celebratory news – cannabinoids have been shown to help breakdown the clumps of protein that lead to Alzheimer’s Disease – and the good news from my research for everyone who prefers to keep their distance from cannabis/marijuana itself is that cannabinoids are part of cell membranes and can be found in many foods in small quantities and in a few foods in larger quantities.   https://www.medicalmarijuanainc.com/dr-titus-insights-alzheimers-research-work-dr-schubert/ – According to this article $200 billion is spent on Alzheimer’s Disease care every year. That would buy a lot of pumpkin seeds.

The article also includes the number 192 – the number of pharmaceutical chemicals that have been anticipated and tested in hope of a cure or effective treatment for Alzheimer’s Disease that have ultimately not been successful. One hundred and ninety two chemicals tested, one hundred and ninety two chemicals found ineffective – cannabinoids however have been found effective at helping the body to naturally break down the tau and  beta-amyloid protein clumps that lead to brain damage and later symptoms of dementia in Alzheimer’s Disease and a few other neurological conditions including traumatic brain injuries and autism. (links re tau/amyloid in autism & Alzheimers) (links re tau/amyloid protein in traumatic brain injury)

So I personally don’t want to wait for number 193, 194, 195, 196, 197, 199 and 200 in hopes that a patent protected chemical treatment can be found to substitute for our body’s natural abilities – I would rather eat pumpkin seeds and other phospholipid rich foods today. Ibuprofen is a pharmaceutical that is no longer covered by a patent and it has been found to be beneficial in protecting against Alzheimer’s Disease (link: https://www.sciencedaily.com/releases/2018/03/180326140239.htm) and the underlying reason is likely that ibuprofen prevents the break down of cannabinoids (book excerpt)(a variety of links) – but you need cannabinoids first and some people might no longer be able to make them after a certain age or state of health or may never have been able to make them as well due to genetic differences.

So celebrate protecting your brain today by eating pumpkin seeds, cardamom spice, Rosemary, chocolate, or leafy green vegetables. – the brightly colored tiny inner part of a piece of corn that you can see when eating corn on the cob is also a good source.

Another source of a variety of beneficial phytonutrients that we tend to discard instead of eating is the white part around oranges and grapefruit – don’t worry about trimming it all away because it is good for us and mild in flavor. The tougher peel also has beneficial nutrients but it is strongly flavored and can be used in tiny amounts to add a lemony flavor to foods, either freshly grated as lemon or orange zest, or it can be purchased in Middle Eastern grocery markets as powdered dried lemon or lime (Citron vert Seche moulu or Limon seco molido, or Arabic, see example). For maximal flavor add the dried lemon or lime after cooking at the table. The flavor rich terpenes that give the lemony flavor can be effected by long cooking times. The boiling point of limonene is 348.8°F.

Disclosure: This information is being provided for educational purposes within the guidelines of Fair Use. While I am a Registered Dietitian is is not intended to provide individualized health care guidance. Please seek an individual health care professional for the purpose of individualized health care guidance. Thanks.

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It is not a coincidence that my phospholipid rich diet overlaps with Nrf2 promoting foods

The punchline – phospholipids are the building block of cannabinoids which are also a phytonutrient that causes an increase in production of Nrf2. (1, 3) The most concentrated source of cannabinoids or phospholipids is found in medical marijuana or the non-euphoric CBD oil which is more likely to be available legally. However there are other legal sources of phospholipids and cannabinoids. The phytonutrients are also found in cocoa beans/baking cocoa/dark chocolate (processing reduces the concentration and availability of the ‘bitter’ tasting nutrients in more processed milk chocolate and chocolate syrup.) Phospholipids add a slight bitter taste to foods which I’ve always been able to taste and tend to prefer. A genetic screening did find that I have a double/ both sets of genes/ difference in my ability to make any chemical with phosphorus – the phospho- part of phospholipids which are important in many chemicals in the body not just cannabinoids. (4 – an open access textbook on phosphorylation)

For example the original Lemonhead TM candies have more flavor to me than the more recent version of lemon flavored Chewy Lemonhead, (lemonhead.com). Bitterness is something we have a specialized set of tastebuds to detect. Our tastebuds have a few specific types and there are some that detect sweet, salty, sour, bitter, and some for Umami (fermented protein/free amino acid/a hint of soy sauce like flavor). Recently reseachers have suggested a set detect starch but sweet is also a starch so it might be similar to the sweet detecting tastebuds. The article explains that the difference between simple sugars and complex, longer chain carbohydrates called polysaccharides, can be detected suggesting there are two types of carbohydrate sensing tastebuds. (2)

Our sense of smell adds a lot more differences to our enjoyment of foods and beverages. Terpenes are particularly good smelling and other phenolic compounds also add aroma. Cinnamon and vanilla, basil, oregano and lemon are all sources of phenolic compounds or terpenes. These were discussed in more detail in the recent post on Nrf2 and diet tips for promoting Nrf2. It is a protein that causes genes that make important antioxidants to become active so it helps protect us against damage from oxidative stress which can be caused by health factors or by real world worries whether an upsetting conversation or bad traffic.

Pomegranate seeds (not the juice) and pumpkin seed kernels are also good sources of phospholipids. The spice cardamom powder is also a good source. See the section The DASH Diet and Pumpkin Seeds on the home page of my other website: effectivecare.info. A salad recipe and more information about genetics and cannabinoids are also available on that site or in the post Is it Starvation or Addiction?

Pomegranate extract has been studied in animal based research to examine in more detail how it helps hypertensive blood pressure problems and reduce oxidative stress. The mechanism was found to involve increasing Nrf2. The formation of mitochondria increased, and their function improved. Before treatment the hypertensive animals had fewer of the specialized proteins that are involved in production of mitochondria. Mitochondria are the cellular organelles primarily responsible for turning blood sugar/glucose into usable energy. (5)

This study uses a pomegranate extract that incorporates the peel, seeds and juice as all contain the bioactive phytonutrient, punicalagin, thought to be most helpful for anti-inflammatory, anti-tumor and anti-diabetic effects. The animals who received the extract were found to have better blood pressure, reduced heart hypertrophy ( a sign of worse heart health) and a lower heart rate. Neuronal/nerve cell activity and oxidative stress markers were decreased in the experimental treatment group compared to the control group which received a saline solution and no pomegranate extract. Angiotensin converting enzyme which is involved in blood pressure control was lower in the experimental group  that received pomegranate extract and may be the mechanism for the lower blood pressure. Pro-inflammatory cytokines were reduced in the experimental group after treatment, an indication that hypertensive inflammation was reduced. The pomegranate extract treatment led to increased levels of phosphorylated AMPK which then leads to an increase in Nrf2 and its resulting increases in antioxidant proteins which protect against injury and inflammation from oxidative stress chemicals. (5)

Pomegranate is referred to as an ancient fruit in a research study on its benefits against hepatocellular carcinoma. Spoiler alert – it was found beneficial. (6)

“PE (Pomegranate Extract) treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC (Hepatocellular Carcinoma).” (6)

One to ten grams per kilogram (1 to 10 g/kg) (6) gives us a quantity but that is of the extract which is made with the juice, seeds and peel. The inner peel is whitish in color while the outer peel is vibrantly colored similarly to the juice. An average adult weighs somewhere around 70 kg (68 kg ~ 150 pounds) so the animal study used an equivalent of 70 to 700 grams of pomegranate extract. Five grams is about a teaspoon so 70 grams would be slightly less than 5 Tablespoons or about 1/4-1/3 cup which is roughly a half a pomegranate worth of seeds with the juice and would be a reasonable serving size. Ten times that would be more than a typical serving at approximately two and a half to three and a third cups of pomegranate extract per day, for 22 weeks (6) – but if you have Hepatocellular Carcinoma that might sound good compared to other chemotherapy treatments.

My health and anxiety seems to be improved with a half a pomegranate worth of the seeds per day, or half in the morning and half in the evening when anxiety is worse. I have not tried using any part of the peel or interior whitish colored membranes so I don’t know what how edible they would taste. Pumpkin seed kernels are a higher fat food and the serving size is about 2 to 4 tablespoons, 1/8 to 1/4 cup as a snack my themselves or sprinkled on a salad. I prefer to have some of both foods every day. As well as other dark green leafy vegetables and herbs, beans, rice, nuts and other seeds, and ground lemon powder and/or lime or lemon juice. One healthy food alone isn’t enough to improve my health and mood on it’s own however the half a pomegranate can improve my mood when I’m having a worse anxiety moment. Pumpkin seed kernels are a higher fat and protein substance and don’t seem to have the quick acting mood lifting effect but I notice when I run out of them and don’t have any for a few days.

Regarding the “ancient fruit” reference in (6), yes pomegranate is mentioned in the Bible, Old Testament; 1 Samuel 14.2, “Saul was staying in the outskirts of Gibeah under the pomegranate tree…” and Old Testament; Haggai 2.19: “Is the seed yet in the barn? Do the vine, the fig tree, the pomegranate, and the olive tree still yield nothing? From this day on I will bless you.” Also pomegranates are mentioned as a decorative feature in a church: “House of the Lord” Jeremiah 52.17, 52.20-23 “As for the two pillars, the one sea, the twelve bronze bulls which were under the sea, and the stands, which Solomon the king had made for the House of the Lord, the bronze of all these things wre beyond weight. 21 As for the pillars, the height of the one pillar was eighteen cubits, its circumference was twelve cubits, and its thickness was four fingers and it was hollow. 22 Upon it was a capital of bronze; the height of the one capital was five cubits; a network and pomegranates, all of bronze, were upon the capital round about. And the second pillar had the like, with pomegranates. 23 There were ninety-six pomegranates on the sides; all the pomegranates were a hundred upon the network round about.”  (7)  So it seems pomegranates were thought quite valuable during Biblical times.

Menu tips to be continued later, Happy holidays!

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. Li X., Han D., Tian Z., Gao B., Fan M., Li C., Li X., Wang Y., Ma S., Cao F.,

    Activation of Cannabinoid Receptor Type II by AM1241 Ameliorates Myocardial Fibrosis via Nrf2-Mediated Inhibition of TGF-β1/Smad3 Pathway in Myocardial Infarction Mice., Cell Physiol Biochem 2016;39:1521-1536, https://www.karger.com/Article/FullText/447855 (1)

  2. Chase Purdy, The human tongue has a sixth sense and its a taste bud that loves carbs. Quartz, qz.com, Sept. 8, 2016, https://qz.com/776857/the-human-tongue-has-a-sixth-sense-and-its-a-taste-bud-that-loves-carbs/ (2)
  3. Wang Y, Ma S, Wang Q, Hu W, Wang D, Li X, Su T, Qin X, Zhang X, Ma K, Chen J, Xiong L, Cao F: Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart. Sci China Life sci 2014;57:201-208. https://www.ncbi.nlm.nih.gov/pubmed/24430557 (3)
  4. Claude Prigent, Editor, Protein Phosphorylation, Publisher: InTech, Chapters published November 29, 2017 under CC BY 3.0 license InTechOpen.com, https://www.intechopen.com/books/protein-phosphorylation (4)
  5. Wenyan Sun, Chunhong Yan, Bess Frost, Xin Wang, Chen Hou, Mengqi Zeng, Hongli Gao, Yuming Kang,and Jiankang Liu,

    Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats., Sci Rep. 2016; 6: 34246.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054377/ (5)

  6. Anupam Bishayee, Deepak Bhatia, Roslin J. Thoppil, Altaf S. Darvesh, Eviatar Nevo, and Ephraim P. Lansky.,  Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms., Carcinogenesis. 2011 Jun; 32(6): 888–896. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314278/ (6)
  7. Holy Bible, Revised Standard Version, Containing the Ole and New Testaments, Thomas Nelson & Sons, New York, 1952, 1 Samuel 14.2, page 297, Haggai 2.19, page 984 https://www.amazon.com/1952-Revised-Standard-Version-Bible/dp/B000U2L3E0 (7)
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Medical marijuana is not the same as an addiction

The need for medical marijuana may be a daily need like any other medication and physical or mental withdrawal symptoms may occur when it is not available just like many other medication.

There can be genetic reasons that someone may need an external source of phospholipids or cannabinoids from food sources throughout their lives for best health or the need may arise during an illness or later in life due to changes associated with aging. The cannabinoid system is involved with many other functions of the body so symptoms can be diverse when there is a lack and cravings for something may occur which may be interpreted incorrectly and other substances may be overused in addictive ways. Overeating food, use of alcohol, nicotine and heroin/opiates products may all be problems that occur with an underlying dysfunction in the person’s ability to make cannabinoids internally the way people of normal physiology are capable. I discuss this topic in more detail and include some legal food sources that are naturally better sources of cannabinoids or phospholipids in an section I wrote for my newer website https://effectivecare.info/addiction-or-starvation%3F

which is also copied onto this site with a few additional details about the salad recipe: Is it Addiction or Starvation?

While I am past the age of having babies, and entered grand parent age the need to reschedule marijuana for the purpose of research may be important for the fertility of younger women and men. The cannabinoid system is essential for both female and male fertility, in a U-shape need – too little or too much can be problems. Overuse of medical or recreational marijuana could interfere with fertility but an underlying deficiency could also be a cause of infertility in either gender.

Infertility problems can be caused by a problem with cannabinoid receptors or an excess or inadequate supply of cannabinoids. Research in the cannabinoid system and its effects on physiology beyond toxicity and addiction are limited due to the federal listing of the cannabis/marijuana plant as a Schedule 1 substance, something considered to have no medical value. However the listing is in error and a number of medical officials and organizations have recommended changing the federal listing. An overview of the research that is available on the cannabinoid system’s role in female and male fertility and reproduction is available here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034092/

The system is involved in the fertilized egg successfully implanting in the woman’s uterus and the cannabinoid system is involved in the male reproductive system in a few ways including the motility of the sperm – are they able to effectively get to where they need to go? A variety of cannabinoids exist and some also have effects on hormonal controls that occur within the brain that effect male reproductive health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651943/

The balance of cannabinoids is critical and too much use of an external source such as medical marijuana is linked to male infertility, however again a U shape need exists. Some is necessary, too much or too little is a problem.

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.