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 MediaDec 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 sclerosisNeuromolecular 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 Foodshttp://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, 154-171http://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 182018, 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)

Average Autism and Alzheimer’s Rates Differ by Gender

Autism is more of a risk for boys than girls by a factor of four boys for every one girl or three boys for every one girl diagnosed with autism depending on the type of study and diagnostic criteria. There is some speculation that autism in girls presents with less obvious symptoms than in boys. Girls with autism may have less repetitive behavior and be able to fit in socially better than boys with autism and may have less obvious focus on one main topic of interest. (1)

At the other end of the age spectrum females have a greater rate of Alzheimer’s Disease than males. (13)

The difference has been shown to be significant, not just a difference in diagnostic criteria. Estrogen is a female hormone that may be protecting girls from the risk of developing autism but then in menopause is no longer protecting older females from the risk of developing Alzheimer’s Disease. Patients with Autism and Alzheimer’s have been shown to have a tendency to have increased amounts of protein clusters (amyloid beta) in the brain which in normal health would be cleared away. An animal based study found a genetic strain of mice with a clear gender and age difference. Young male mice developed autism like symptoms and older female mice developed Alzheimer’s like symptoms.

A different study found a gender difference in the amount of a protective protein (ADNP) in young male mice with autism like symptoms and older female mice with Alzheimer’s like symptoms. (6) Complete lack of the protective protein leads to very early death with neural tube defects in animal studies.  (7) The neuroprotective protein (ADNP) seems to promote autophagy (our body’s recycling method, it makes us more energy efficient and helps detoxify/remove old cells or material such as the beta-amyloid protein for reuse, read more:  14) and the deficit of it may also be involved in schizophrenia. (8) The protein is involved with control of the dendritic branching of brain cells which is typically found to be  different in children with autism. The protein also plays a role in regulating over 400 genes involved in embryo development including ApoE and the tau protein which is found to collect in the brains of patients with Alzheimer’s Disease in addition to beta-amyloid protein. (9)

The role of apoE involves membranes, cholesterol, cannabinoid receptors and lipid rafts – chemistry geeks have fun, three dimensional drawings and a discussion of cholesterol within the brain and its role in several neurodegenerative diseases is available online in full text, the brain includes 25% of the body’s cholesterol even though the brain only accounts for 2% of the total body weight, on average. (10).  A briefer description of the role apoE plays in the brain and with estrogen and Alzheimer’s risk is available with a discussion of the gene differences that are known to increase but not guarantee risk of developing Alzheimer’s Disease. (11)

Disclosure: a genetic screening suggests I do have one of the higher risk differences in the ApoE gene. (rs2254958)

Strategies to help increase autophagy may help reverse some of the risk factors associated with reduced ApoE/reduced ADNP levels –

  1. vigorous exercise,
  2. a ketosis promoting, low carbohydrate diet, regularly or occasionally,
  3. fasting for a day or a partial day occasionally. (14)

The activity of the apoE protein on other genes can be affected by cannabinoids, too little cannabinoids may be a problem or too much.

The take home point – magnesium and adequate cannabinoids seem to be involved in helping clear the protein clusters during normal health.

  • Nutritional strategies recommended to help prevent Alzheimer’s disease include increasing intake of magnesium. Research has found that low levels of magnesium promoted build up of  beta amyloid protein while high levels of magnesium promoted breakdown of the misshapen proteins.

“Lab studies show that magnesium modulates enzymes involved in amyloid beta production; at low levels, magnesium favors amyloid beta buildup, while at higher levels it favors amyloid beta breakdown.101,102″ [2]  (from a  2014 post)

Certain genetic conditions and chronic health conditions or older age can make the body less able to make cannabinoids endogenously/internally. External sources of cannabinoids have been shown to be helpful for clearing the protein clusters involved in Alzheimer’s Disease. (https://www.sciencedaily.com/releases/2016/06/160629095609.htm)

An underlying infection with bacteria or yeast may be involved in the buildup of the protein clusters as they have a protective effect against some types of infection, so addressing low grade chronic infection may be needed to help stop the over production of the amyloid beta protein clusters in addition to providing adequate magnesium and cannabinoids. Note that there are non-euphoric cannabinoids and legal food sources in addition to medical marijuana. Pumpkin seeds are a good source, $200 billion per year is estimated to be spent on Alzheimer’s care annually at our current rate of the disease prevalence – that would buy a lot of pumpkin seeds. (15 )

That article also mentions that 192 pharmaceutical chemicals have been anticipated and tested in hope of a cure or effective treatment for Alzheimer’s Disease but which have ultimately not been found to be successful. One hundred and ninety two chemicals tested, one hundred and ninety two chemicals found ineffective – magnesium and 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. (15 ) (links re tau/amyloid in autism & Alzheimers) (links re tau/amyloid protein in traumatic brain injury)

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: 16) and the underlying reason is likely that ibuprofen prevents the break down of cannabinoids (17)(Search term: “ibuprofen prevents break down of cannabinoids”) – 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, the herb rosemary, chocolate, or leafy green vegetables. – and 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.

  • The misshapen tau/amyloid-beta proteins have a protective effect against bacteria and the yeast Candida albicans so a chronic lowgrade infection may be an underlying cause of the accumulation of beta amyloid placques. [3] [4] (from a  2014 post)

There are many more legal food sources of cannabinoids or a precursor available, a longer list is included below. The progression of Alzheimer’s Disease can take twenty years before symptoms are obvious, so getting an early start on protecting against the tau/beta-amyloid protein build-up makes sense to me (Disclosure, I have a direct family history of the disease in older relatives and a genetic screening suggests that I am more at risk, so I am biased towards preventing the disease in my own brain or other family members.)

Phospholipids are part of cannabinoids and other phosphorus containing nutrients are important in energy production. The phospholipids and cannabinoids are important for the health and function of skin and other membranes lining cells and organs, and/or if you care more about having a good hair day than whether you might get Alzheimer’s Disease in several decades, then the phospholipids are also important for hair growth: *The phospholipid mixture in this animal-based study was applied on the skin surface for hair loss associated with inflammatory skin dermatitis: (18)

(Additional Discloure: I am also genetically at risk for Male Pattern Baldness which became visibly apparent when my autoimmune disease was more severe, however with my switch to phospholipid rich foods my hair has since grown back and my autoimmune condition is in remission as long as I continue with my new health habits).

Other nutrients including the B vitamins, vitamin E, and zinc are also important for healthy hair growth (read more) but many of the following list would also be good sources of B vitamins, vitamin E, zinc and other trace minerals and essential omega 3 and omega 6 fatty acids. Pumpkin seeds are a good vegetarian source of zinc, otherwise the mineral is more commonly available in meats.

  • Food Sources of Phospholipids and other phospho-nutrients: 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)

That topic took a walk around the block and picked some daisies along the way but the important message might be that eating well and exercising regularly may promote healthy hair, a fit body right now while helping maintain healthy brain function into the future. Genetic susceptibility may be involved in the rate of young males with autism and older females with autism and prevention might include more magnesium and phospholipid rich foods in the diet with a diet that is moderate in carbohydrates and regular vigorous exercise to promote autophagy to help promote the natural recycling of tau and beta-amyloid protein that tends to accumulate in the brains of people with autism and Alzheimer’s Disease. Lack of ADNP protein may lead to lack of ApoE or a genetic difference may cause reduced ApoE and the deficiency may lead to a reduced level of autophagy.

Fasting for a day or partial day occasionally or a low carbohydrate diet, even just a diet balance as low as 30% of calories, and vigorous exercise are three natural ways that may help promote autophagy – our body’s natural method for removing and reusing old cellular material. (14) Those strategies might help a woman with Alzheimer’s risk but for an infant or toddler may need to be adapted to simply allowing vigorous, safe play, and a diet that with a greater percentage of healthy fats than average. The list of phosphonutrient rich foods are generally healthy and safe for prenatal diets or other stages of life and would likely promote a fit body and healthy hair for a person of any age and gender – and what is good for the hair is good for other membranes throughout the body and is also good for the brain. The hair is a protein that is a modified form of skin tissue and so is fingernail protein – beauty is more than skin deep.

Some daisies.

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. Thanks.

  1. Sarah Deweerdt,  Estimate of autism’s sex ratio reaches new low, April 27, 2017,  spectrumnews.org https://www.spectrumnews.org/news/estimate-autisms-sex-ratio-reaches-new-low/ 
  2. Liam Hawkins, Nutritional Strategies and Alzheimers, March 2013 lifeextension.com, http://www.lifeextension.com/magazine/2013/3/Nutritional-Strategies-to-Combat-Alzheimers/Page-02
  3. Lisa Conrick, What is Causing Beta-Amyloid Production in Alzheimer’s and Autism?, Oct. 23, 2012, ageofautism.com, http://www.ageofautism.com/2012/10/what-is-causing-beta-amyloid-production-in-alzheimers-and-autism.html
  4. Molnar Mark, Alzheimer’s Disease Emerging Role of Infection,  http://miklossy.ch/
  5. Why women have more Alzheimer’s disease than men: gender and mitochondrial toxicity of amyloid-beta peptide. J Alzheimers Dis. 2010;20 Suppl 2:S527-33. https://www.ncbi.nlm.nih.gov/pubmed/20442496
  6. Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer’s pathologies. Transl Psychiatry. 2015 Feb 3;5:e501. https://www.ncbi.nlm.nih.gov/pubmed/25646590
  7. Shmuel Mandel, Gideon RechaviIllana Gozes, Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis. Developmental Biology, Volume 303, Issue 2, 15 March 2007, Pages 814-824. https://www.sciencedirect.com/science/article/pii/S0012160606013960

  8. Shlomo Sragovich, Avia Merenlender‐Wagner, Illana Gozes, ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer’s Disease. BioassaysVolume39, Issue 11, November 2017, Pages 1700054 https://onlinelibrary.wiley.com/doi/pdf/10.1002/bies.201700054

  9. Gozes Illana, (2015) Activity-dependent neuroprotective protein (ADNP): from autism to Alzheimer’s disease. SpringerPlus. 4. L37. 10.1186/2193-1801-4-S1-L37.  https://www.researchgate.net/publication/282802744_Activity-dependent_neuroprotective_protein_ADNP_from_autism_to_Alzheimer’s_disease
  10. M Maccarrone, G Bernardi, A Finazzi Agrò, and D Centonze, Review: Cannabinoid receptor signalling in neurodegenerative diseases: a potential role for membrane fluidity disturbance. British Journal of
    Pharmacology, Themed Issue: Cannabinoids in Biology and Medicine, Part I, Nov. 16, 2010. http://files.iowamedicalmarijuana.org/petition/2012/bjp-aug-2011-1379-1390.pdf
  11. Hilary Lampers, ND, 5 Reasons to Know Your APOE:  Understanding Your Alzheimer’s Disease Risk. June 13, 2016 thenatpath.com
  12. http://thenatpath.com/body/5-reasons-to-know-your-apoe/
  13. Maxwell A. Ruby, Daniel K. Nomura, Carolyn S. S. Hudak, Lara M. Mangravite, Sally Chiu, John E. Casida, and Ronald M. Krauss, Overactive endocannabinoid signaling impairs apolipoprotein E-mediated clearance of triglyceride-rich lipoproteins. Proc Natl Acad Sci U S A. 2008 Sep 23; 105(38): 14561–14566. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567196/

  14. Nick English, Autophagy: The Science-Backed Way to Cleanse Your Body, July 4, 2016, greatist.com, https://greatist.com/live/autophagy-fasting-exercise
  15. Stuart W Titus, PhD, Dr. Titus’ Insights: Alzheimer’s Research and the Work of Dr. Schubert, Aug. 5, 2016, medicalmarijuanainc.com,  https://www.medicalmarijuanainc.com/dr-titus-insights-alzheimers-research-work-dr-schubert/
  16.  Neuroscientists say daily ibuprofen can prevent Alzheimer’s disease., March 26, 2018, sciencedaily.com,   https://www.sciencedaily.com/releases/2018/03/180326140239.htm

  17. K. D. Rainsford, IbuprofenDiscovery, Development and Therapeutics. 
    John Wiley & Sons, June 25, 2015, page 134, https://books.google.com/books?id=CAcLCgAAQBAJ&pg=PA134&lpg=PA134&dq=ibuprofen+prevents+break+down+of+cannabinoids&source=bl&ots=oJ_cjSrWXr&sig=yQgwSrdZOkA1MNDkbf7EF7waItY&hl=en&sa=X&ved=0ahUKEwjf7ZKPrcnaAhVlneAKHeDyAuAQ6AEIlQEwCA#v=onepage&q=ibuprofen%20prevents%20break%20down%20of%20cannabinoids&f=false
  18. Seong-Hyun Choi, Jeong-Su Moon, Byung-Suk Jeon, Yeon-Jeong Jeon, Byung-Il Yoon, and Chang-Jin Lim, Hair Growth Promoting Potential of Phospholipids Purified from Porcine Lung Tissues. Biomol Ther (Seoul). 2015 Mar; 23(2): 174–179. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354319/
  19. ADNP related syndrome FTNW, *lack of ADNP genetically leads to reduced muscle tone and can cause eating problems in children. https://www.rarechromo.org/media/information/Chromosome%2020/ADNP%20related%20syndrome%20FTNW.pdf

Genetic Screenings can give guidance about potential medication adverse reactions.

I had a more complete ancestry.com genetic screening done and an independent (for research/personal use only) analysis of the raw data showed that I have an impaired ability to process drugs including olanzapine. (Note for new readers, I had a very bad reaction to that drug, and am not alone per some patient forum feedback by others who had trouble with it causing very bad mood changes when trying to stop using it. Get the genetic screening done first would be my strongly worded advice – suicide and homocide has been associated with withdrawal from the drug and it can cause diabetes and significant weight gain while using it.)  https://www.snpedia.com/index.php/gs155

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 it 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.

Chronic illnesses that I may be more prone to include inflammatory intestinal disease https://www.snpedia.com/index.php/rs2241880 and other autoimmune conditions and Type 1 diabetes. I may produce less insulin than average. https://www.snpedia.com/index.php/rs7574865

and suicidal ideation with depression and/or bipolar disorder. https://www.snpedia.com/index.php/rs10748045

I may have reduced MOAO activity which means reduced breakdown of brain neurotransmitters that affect mood. rs6323(T;T)

And reduced drug metabolism which could affect dosage of some immune suppressing and cancer treatment drugs. https://www.snpedia.com/index.php/rs1800460

A few areas may increase my risk of heart disease, especially with a high fat diet, and especially if stress-related, cortisol induced,  https://www.snpedia.com/index.php/rs6318   and I may have increased risk for aortic or brain aneurysm (weak blood vessels bursting – lovely – but not really a surprise with my severe migraine history – it always felt like something was wrong with my blood vessels in one area of my brain that MRI showed I had “tortuous” twisted shaped vessels – okay – meditating calmly about all that, thanks.)   https://www.snpedia.com/index.php/rs10757278

Heart attack/cardiac arrest is at increased risk if I also have hypertension (which I don’t – magnesium rich diets are associated with reduced risk of high blood pressure). https://www.snpedia.com/index.php/rs187238

while other genetic differences may decrease my heart disease risk; and vigorous exercise may be needed for me to be able to maintain a healthy weight. I may be able to lose weight easier on a low fat diet; and more likely to gain on a high saturated fat diet. https://www.snpedia.com/index.php/rs5082

Another is associated with increased obesity risk, there may be a disruption/decrease “loss of mitochondrial thermogenesis.” – in other words, inefficient energy production by the cellular structures that turn glucose sugar into usable energy. https://www.snpedia.com/index.php/rs1421085

It involves a protein that is an enzyme and is called more simply the FTO protein or more chemically, the – “alpha-ketoglutarate-dependent dioxygenase FTO is an enzyme that in humans is encoded by the FTO gene located on chromosome 16” – Wikipedia/FTO gene. FTO stands for Fat mass and obesity-associated protein. The protein is involved in demethylating DNA/RNA strands – which means it is involved in activating other genes. Methyl groups are an Oxygen-Hydrogen group, potentially one part of the water molecule when combined with one more Hydrogen, and when a DNA/RNA genetic strand is fully methylated in any potential bonding areas then the gene is inactive, methyl groups are a little like an off switch for the gene. So to not have the FTO enzyme I would be unable to turn some genes to the active/on phase. Clinical trials/observation of patients with the genetic difference found what was not turned off was the appetite, significantly more calories (125-280 Kcal) were eaten each day compared to control group subjects who didn’t have the difference. The difference is also associated with decreased verbal fluency, frontal lobe size and an increased risk for Alzheimer’s Disease. Wikipedia/FTO gene. What to do about it is not mentioned.

I do have genes associated with an increased childhood sensitivity to bitter flavors that may become as an adult, taste that is more accustomed to the flavor. https://www.snpedia.com/index.php/gs227

The screening does show a folate, B vitamin, difference similar to that found in a more specific genetic screening designed to reveal autism related differences that I had done with a different company a few years ago. The difference would increase my need for folate as my ability to process it may be only 10-20% of normal, and the lack of folate can increase the risk of excess build up of a chemical (homocysteine) associated with heart disease risk, especially if I was also low in B12 and B6.  https://www.snpedia.com/index.php/rs1801133

I may have increased risk for breast cancer. rs2981582(C;T)

Genetic screenings are just a possibility, not a sure thing. I have a 99% likelihood of having blue eyes – but I don’t, I have green eyes.   https://www.snpedia.com/index.php/rs12913832 

Although I may have increased risk of scoliosis – which I do have a slight case of – https://www.snpedia.com/index.php/rs11190870

There is an increased chance that I’m optimistic and handle stress well – isn’t that swell? rs53576(G,G) (No link because this is a long file and it is starting to not respond, I am using a slow internet speed.)

Normal (A2/A2) Better avoidance of errors. Normal OCD risk, normal Tardive Dyskinesia risk, lower ADHD risk. Less Alcohol dependence. Higher risk of Postoperative Nausea. Lower obesity. Bupropion is effective.”  – Bupropion is a psychiatric medication that I did find helpful for years but eventually developed some side effects and stopped using it.

The genetic screening was done by ancestry.com and the raw data from the screening was processed independently (small fee) by the promethease.com website.

It may be clear that genetic screening is a complex topic and is for general health guidance rather than diagnostic purposes although the drug sensitivity information is used by medical professionals in some areas of treatment.

A couple other positive gene differences may provide me a better than average memory and muscle fibers that are better for moving fast – sprinting.

  • 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. 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.