Tag: phospholipids

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Cannabinoids are made with the BHMT gene (and others).

Cannabinoids are complex molecules we can make when genetically and nutritionally, healthy and nourished. Various genetic differences are known that cause a deficiency in endogenously made cannabinoids – phospholipids. Lack of cannabinoids negatively effects many areas of health throughout the body and brain, the mood and decision making, and appetite, and movement are all affected by cannabinoid availability.

It is discrimination to prevent research from occurring into the medical benefits of cannabis and cannabinoids and to prevent people who need an external source from having access to it. Covid and LongCovid may be increasing the number of people who might benefit from an external source as epigenetic changes or some other effects of the viral infection may be causing dysfunction in normal production of cannabinoids or some other problem.

Cannabinoids and the Cannabinoid receptors perform many functions in the body.

Membranes and growth of tissue is affected directly as building blocks that are part of the membranes, and indirectly as messenger chemicals that help promote and guide growth.

Cannabinoids also have widespread effects on immune function in addition to brain and nerve function. Cannabinoid receptors are found throughout the brain and also on white blood cells, leukocytes. Our immune function also needs endogenous, internally made, cannabinoids, or would benefit from an external source if endogenous cannabinoids were not able to be made normally.

“In human leukocytes the expression of cannabinoid receptor mRNA has been reported to be lower than that found in brain tissue. The message has, however, been detected in all subsets of leukocytes examined. The message levels are greatest in S cells, followed sequentially by natural killer cells (NK), polymorphonuclear neutrophils (PMN), T8 cells, monocytes and T4 cells.” (11)

Leukocytes help us fight viral infections and patrol for other infectious pathogens or precancerous or cancerous cells. Nutrients work together, synergy – increased power together than any on their own. We need magnesium for leukocytes to be able to perform the killing, apoptosis, and we need niacin to help with the safe removal of debris or engulfing of virus or small cells. Cell contents that are spilt into surrounding tissue has to be removed or it causes more inflammatory damage and can lead to death of other cells.

Niacin reduces inflammation for us in some direct ways and indirectly by inhibiting the NF-kB inflammatory pathway. Deficiency may increase neurodegeneration as well as reduce immune function for fighting virus or cancer.

“Reports suggest that deficiency of niacin can increase the risk of neurodegeneration, immunological disorder and inflammation stress [14]. Additionally, niacin exerts its anti-inflammatory effect by suppressing the NF-κB pathway [15].” (18)

The cannabinoid system is also involved in neurotransmitter levels.

“According to previous studies, CB1r [Cannabinoid Receptor type 1] is located in the locus coeruleus (LC) and in the dorsal raphe nucleus (DRN), and it regulates noradrenaline (NA) and serotonin (5HT) release, respectively, by the modulation of GABAergic and glutamatergic terminals (117, 118).” (17)

Problems with the endocannabinoid system can affect mood such as changes in serotonin leading to anxiety or depression. Adequate niacin intake helps preserve our serotonin levels by sparing tryptophan.

“Genetic studies pointed out interesting results regarding the involvement of polymorphisms or epigenetic modifications of CNR1 as susceptibility/risk biomarkers to develop anxiety disorders. Lazary and cols. analyzed the interaction of the promoter regions of the serotonin transporter (5HTT; SLC6A4) and CNR1 genes on anxiety. Specific constellations of CB1r and 5HTT promoters were closely associated with high or low synaptic 5HT concentrations, which could result critically in the vulnerability to experience an anxiety disorder (124). Hay and cols. employed CRISPR/CAS9 technology to disrupt a highly conserved regulatory sequence (ECR1) of the gene encoding CB1r (CNR1).” (17)

Cannabinoid system differences occur in ethnic & gender groups. We may be equal but we are not all the same.

Who has the gene differences may vary with ethnicity. “With 60 DNA samples (120 alleles) for each of the 4 ethnic groups studied, we had 90% power to detect a variant allele with a true population frequency of ≥ 2% [16]. ” “Twenty-five SNPs were observed in BHMT — 17 in AA, 8 in CA, 9 in HCA, and 10 in MA subjects (Table 1 and Fig. 2 upper panel).” (1) Number of cannabinoid receptors has been found to vary based on ethnicity and gender with people of Caucasian background having the most, people with African/black background having slightly fewer, and Asian having significantly fewer than those of people with Caucasian or African ethnicity. (11)

“The relative levels of the 58 kDa CBI protein 1070 E.S. Onaivi et al. from the male volunteers were, 47.4%; 39.0% and 13.6% for the White, Black and Asian blood samples respectively as shown in Fig. 3. The relative levels of the Cl31 protein in the male and female volunteers were 49.6%, 32.2% and 18.2% for the white and black females in comparison to the black male blood samples respectively as shown in Fig. 4. Therefore in both males and females, the cannabinoid receptors appear to vary by gender and ethnicity, for example Fig. 3 show white male > black male > Asian male and Fig. 4 show white female > black female > black male.” (11)

African Americans were found to have variations in the BHMT gene almost twice as often than Caucasian and Mexican-American ethnic groups and Hans Chinese American were least likely (small group study). (1)

The BHMT gene and Endogenous Cannabinoid production & breakdown.

The BHMT gene encodes an enzyme involved in homocysteine metabolism and the production of amino acids methionine, and dimethylglycine from betaine. (2) The BHMT enzyme is visualized in a graphic of the folded shape, made up of four parts, monomers, coupled into two sets of dimers, figure C: (1.1).

The BHMT enzyme is also involved in about 60% of the glycerophospholipid production pathway (2) which means important cannabinoids may not be able to be made internally and would need to be obtained in the diet or other sources or suffer deficiency symptoms chronically. People with Cystic Fibrosis also can’t make cannabinoids however the fatty acid end of the molecule is what can’t be made normally. The BHMT gene difference would disrupt production of the glycerophosphate end of the larger cannabinoid molecule. PA, PE, PI, and PS production might be reduced or dysfunctional and breakdown of LPC and LPE which might lead to some types of cannabinoids being unavailable and others unable to be broken down and remove normally so excess might collect -unknown by me. (3)

  • Phospholipids: PA, phosphatidic acid; PE, phosphatidylethanolamine; PC, phosphatidylcholine; PS, phosphatidylserine; PG, phosphatidylglycerol; CL, cardiolipin; PI, phosphatidylinositol. (15)
  • LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine, (19)

Research in cannabinoid chemistry was limited to toxicity or addiction due to the rescheduling of marijuana by the Nixon administration as nonmedical. Since the differences in function of the endocannabinoid system varies with ethnic group it is somewhat genetic discrimination to as well as racial discrimination to target an ethnic group with a law that wouldn’t affect all ethnic groups equally. Someone unable to make cannabinoids would have more craving and physical need for a rich source of phospholipids or cannabinoids, than a person with normal ability to make cannabinoids and/or a low or normal amount of cannabinoid receptors compared to someone with many of them.

Cannabinoid receptors effect mood, & may be involved in anxiety, depression, and possibly suicide.

Lysophosphatidylcholine, LPC, can cause an increase in calcium flow into cells at an atypical cannabinoid receptor GPR55 (4, 5) which is excitatory. Over activity, excess calcium entry, might be a negative to cell health. During normal activation levels the atypical cannabinoid receptor has anti-depressant effects and may help prevent suicide as the brains of suicide victims have fewer GPR55 receptors than typical. (14)

“This result, plus the observation that GPR55 increases intracellular calcium, suggests that GPR55 activation enhances neuronal excitability. These findings, together with the preferential expression of GPR55 on large-diameter DRG neurons, which can be involved in nociception, particularly in neuropathic or inflammatory pain states (29–31), suggest that GPR55 may have a pronocioceptive [pain increasing] role.” (5)

So overactivity of the GPR55 receptors might be perceived as chronic pain and might affect mood and suicidal ideation. Cannabinoid receptors in the prefrontal cortex (CB1) are also known to be involved with suicide risk from research with people suffering from anorexia (17) or alcoholism and depression. (16)

Cannabinoids also can reduce oxidative stress & inflammation, and may be helpful for preventing or treating neurocognitive degeneration conditions.

Calcium can cause oxidative stress damage and would be increased during times of strenuous activity or infection or other times of increased metabolism. THC can cross the blood brain barrier and can help reduce oxidative stress and may be helpful for treatment of neurocognitive degeneration. It was found to improve glucose use within cells and improve brain function in other ways with no toxicity problems in an animal based study. (12)

“In silico analysis predicted THC to be permeable across the blood-brain-barrier. THC was also predicted to have an oral LD50 and toxicity class values of 482 mg/kg and 4 respectively. These results indicate that C. sativa improves glucose consumption with concomitant suppression of oxidative stress and cholinergic dysfunction, and modulation of purinergic and gluconeogenic activities in brain tissues.” (12)

Personal experience – I have a double BHMT allele – it isn’t something I would recommend trying yourself.

I have experience of a lifetime without typical cannabinoid production and the symptoms that may cause. There is a double allele of my BHMT gene which means I can not make some endocannabinoids and can’t break down others. A double allele means both copies contain the same difference from typical. (post, see # 3 in the first list) So I can’t make the BHMT enzyme at all. I supplement with dimethylglycine and methionine since finding out and it helped. I need to continue daily though as genetic metabolic differences mean lifelong symptoms of deficiency of the nutrients that are affected, or an excess of a chemical metabolite that normally would be broken down sooner so it wouldn’t collect.

Post: Clinical Endocannabinoid Deficiency, (CED), and phospholipids. Excerpt:

Conditions that may involve Clinical Endocannabinoid Deficiency, (CED):

Conditions that may involve a deficiency in cannabinoids chronically may include symptoms of pain, muscle spasms, nerve numbness, mood disorders, movement disorders, digestive and appetite problems, appetite and growth failure in infants or colic, menstrual problems and infertility/miscarriages and hyperemesis prenatally.

  • Pain/inflammation: Migraines, Fibromyalgia.
  • Mental health: Anxiety, PTSD, Major Depression, Bipolar disorder, Motion Sickness, The balance of cannabinoids (2-AG ~ noneuphoric CBD and anandamide ~ euphoric THC) is a problem in schizophrenia. There is too much of the anandamide, excess THC can cause schizophrenia like symptoms, and providing CBD may help patients. *See this post for more nutritional deficiencies that cause schizophrenia like symptoms, five or more may be involved, suggesting the problem is a symptom rather than a condition with a single cause – and a single cure: The voices that people with schizophrenia are hearing are probably their own inner thoughts.
  • Nervous system: Multiple sclerosis, Diabetic Neuropathy, Brachial plexopathy, Causalgia, Phantom limb pain, Glaucoma, Huntington’s, Parkinson’s, Cystic Fibrosis,
  • Appetite/digestive system: Anorexia & Bulimia, Neonatal Failure to Thrive, infantile Colic, Irritable Bowel Syndrome.
  • Fertility/reproductive system: Dysmenorrhea, Hyperemesis, repeated miscarriages (Russo 2016), (anandamide is needed for implantation of a fertilized egg in the uterus and development of the placenta to occur normally, too much or too little can disrupt the process, Fonseca 2013), male infertility due to sperm motility problems is associated with low levels of anandamide (AEA) (Amoako 2013), (too much can also negatively affect male or female fertility). *See this post for more details about infertility and phospholipids: (Phospholipid or phosphorylation deficiency: Potential symptoms)
  • Other food sources of cannabinoids exist in addition to marijuana or hemp however the amount provided is in lower concentrations so you might need a large salad that includes several sources at one meal, and other sources in beverages, supplements, or at other meals.

— Addition to the excerpt – the amount of cannabinoids in medical marijuana is a lot more, and more likely to be obviously helpful, than the amount of phospholipids or cannabinoids found in a few foods and spices. Sadly medical marijuana has been stigmatized and illegal for many decades. Research into medical benefits was prevented with Richard Nixon’s administration rescheduled cannabis as having no medical value. Research was only possible on addiction or toxicity. Marijuana/cannabis not only has medical value, it has been used medicinally or in other ways by humans for thousands of years. Paper and rope made from hemp fiber was also a large industry prior to making cannabis illegal.

Conditions I’ve had symptoms of which might be due to Clinical Endocannabinoid Deficiency.

The conditions/symptoms I’ve had over my life from the above list include: Migraines, Fibromyalgia; Anxiety, PTSD, Major Depression, Bipolar disorder; Anorexia & Bulimia, Irritable Bowel Syndrome; and some nerve/numbness symptoms since childhood – dystonia.

The amount of cannabinoids a human needs if they are unable to make them internally/endogenously is not readily available information due to the lack of research. The amount of medical marijuana that I find necessary to feel nerve flow in my fingers and throughout my body and to have other symptoms improve is quite a bit each day. It adds up in money to buy, and time and stigma to use.

Smoking is frowned upon by society and cannabis use is still treated as if it is just an addiction or even criminal (which it still is at the Federal level), so it frightens some people to even learn that you use it, or have used it recently. Chronic users have adapted a tolerance to it (8), and mentally may be more used to functioning with some than going without. The type of strain is important for the terpenes that provide different aroma also provide different health effects. Some can be calming for anxiety (limonene), and another sleep inducing and pain relieving (myrcene).

Daily use every 2-4 hours is what I find helpful and smoking has benefits for dosing. Edibles take longer to feel an effect and then suddenly can be too much. Inhalation effects are fairly immediate and easy to know then when enough has been absorbed. The forms of cannabinoids that are absorbed may vary too with the different intake routes, and inhalation may be more effective for some types of health problems than edible/intestinal absorption. The healthiest I’ve ever felt was when I combined eating some fresh trim or immature buds everyday or edibles along with some smoked bud.

Smoke toxins are a negative that causes the “dopey” effect of the stereotypical marijuana user. Vaping devices exist that heat the bud to a lower temperature so the burnt toxins are not created, however some of the THC conversion occurs at higher temperatures so symptoms may not be helped as much. The vape oil products may have other negative effects on the lungs due to the oil and flavorings being inhaled into the lungs where it can add to pneumonia risk.

How much THC am I getting throughout a day then? Possibly 40% of whatever was in the marijuana you smoked – a lot is lost when you burn the buds. 8 There is approximately 525 mg in an eighth of good medical grade marijuana with 15% THC. (6) That eighth ounce might cost $45-60. One gram per day of 10% THC marijuana might provide 40% of the 100 mg of THC it contains, if smoked vs made into an edible. A quarter to half of a one gram joint every 2-4 hours might be giving 10-20 milligrams of THC each time. Strains that also provide some CBD are important as the cannabinoids work together to do somethings in the body such as inhibit mast cell activation.

Eighty to hundred milligrams of THC is suggested as possibly feeling like an excessive dose all at once for someone with increased tolerance, while 25-80 range might be the typical preferred dose. (8)

I have not calculated this for myself before so it does bring up an interesting question of whether I’m getting too much, or enough, or not enough – the fact that I felt best while also eating fresh trim and other edibles regularly would suggest to me that it is not enough when only smoking and that I do need quite a bit daily.

The non-euphoric CBD has been found safe for use even at 1500 mg per day, though 20-40 mg might be more typically used. (7)

Dronabinol is a capsule form of a THC like medication and it might be prescribed at a 2.5 mg dose twice per day. That might seem like a lot to a new user and not that big of a dose to someone else, although the lack of CBD may be a problem if anxiety is a side effect.

Tolerance levels can reduce after not using for a while and then build back up again. Doses that would seem intense for a new user would not really affect a long term user. (8) Genetics may play more of a role in these differences too, lack of research leaves some questions unasked.

Genetic differences occur in the number of cannabinoid receptors which can effect tolerance for a concentrated source such as medical marijuana.

There can be genetic differences where a person doesn’t make cannabinoids well and has lots of extra cannabinoid receptors, all wanting/ready for cannabinoid activation – but with none or to little available. They might tolerate and prefer a larger dose of THC. Other people might have normal amounts of cannabinoid production and like a smaller dose or none, might not like it. For me it provides feeling throughout my body in a way that I don’t have otherwise. It helps me for muscle knots or spasms and pain. Mentally it helps me with PTSD and anxiety and prevents mast cell histamine excess and hyperexcitability.

Cannabinoids help with learning & forgetting – reshaping nerve pathways – neural plasticity. Pain signal pathways can also be remade more easily with cannabinoids.

Cannabinoids help with learning and nerve flow, and with forgetting – changing nerve pathways to build new as needed and remove the old as they are not needed (old phone number for example). Neural plasticity – changing nerve pathways and synapses between nerves is a function involving cannabinoids. Pain and movement, appetite and growth, cannabinoids affect many functions of the body and neural plasticity can affect pain pathways too – remembered pain in an amputee’s healed wound, and maybe feelings of the missing limb still being there also.

“The same team noted a baseline fragility of serotonergic systems in migraine and fibromyalgia [89], plus the co-occurrence of primary headache in 97% of 201 fibromyalgia patients. In a later study [67], they supported the concept that both disorders represented a failure of serotonergic analgesia and NMDA-mediated neuronal plasticity.” (9)

Synergy – many nutrients work together to perform any action in the body. Magnesium also helps inhibit excess pain nerve signals.

Pain conditions can be caused by deficiency of nutrients or chemicals that inhibit pain sensing nerves. Magnesium is needed to inhibit them as well as cannabinoids. Migraine pain may be not responsive to opiate pain killers. (9)

“A trigeminovascular system has long been implicated as integral to the pain, inflammation and secondary vascular effects of migraine, linked through the NMDA/glutamate system [49]. Cannabinoid agonists inhibit voltage-gated calcium channels, and activate potassium channels to produce presynaptic inhibition of glutamate release [50], without dissociative effects noted with other NMDA inhibitors, such as ketamine.” (9)

*Having adequate potassium and magnesium in the diet and avoiding excess glutamate in seasonings and other dietary sources can also help avoid migraines – in addition to the cannabinoids or cannabinoid receptor agonists – activators.

Diabetes pain may also not be helped by opiates unless magnesium is also provided – and providing magnesium in a larger dose helped even more! (10)

Give the body what it needs to function and it functions. Miracle!

Sunshine might be part of the miracle too – vitamin D represents a group of chemicals which may aid us in ways we don’t know yet. Supplementing with one – vitamin D, may not be providing us others that we would have made if sun or full spectrum/UVB containing light is available. (13)

We need cannabinoids too – and some of us genetically can’t make them – since birth, and potentially – epigenetic changes might be occurring that cause dysfunction in a person’s ability to make cannabinoids at some point later in their life. Is that happening in LongCovid survivors? -discussed in the last post.

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.

Reference List

  1. Li F, Feng Q, Lee C, et al. Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization. Molecular Genetics and Metabolism. 2008 Jul;94(3):326-335. DOI: 10.1016/j.ymgme.2008.03.013. https://europepmc.org/article/med/18457970
    1. Figure 3, https://europepmc.org/articles/PMC2515933/figure/F3/
  2. BHMT Gene (Protein Coding), Betaine–Homocysteine S-Methyltransferase: BHMT Pathways & Interactions, genecards.org, https://www.genecards.org/cgi-bin/carddisp.pl?gene=BHMT#pathways_interactions
  3. Glycerophospholipid biosynthesis, reactome.org, https://reactome.org/PathwayBrowser/#/R-HSA-1483206
  4. Drzazga A, Sowinska A, Krzeminska A, Rytczak P, Koziolkiewicz M, Gendaszewska-Darmach E. Lysophosphatidylcholine elicits intracellular calcium signaling in a GPR55-dependent manner. Biochem Biophys Res Commun. 2017 Jul 22;489(2):242-247. doi: 10.1016/j.bbrc.2017.05.145. Epub 2017 May 26. PMID: 28552522. https://pubmed.ncbi.nlm.nih.gov/28552522/
  5. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A. 2008;105(7):2699-2704. doi:10.1073/pnas.0711278105 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268199/
  6. Understand Cannabis Weights & Calculate THC Dose, June 5, canuvo.org, https://canuvo.org/cannabis-weight-calculate-thc-dose/
  7. CBD Dosage: Figuring Out How Much to Take, healthline.org, https://www.healthline.com/health/cbd-dosage#safety-and-side-effects
  8. Barreda AR, De Leon K and Urmasa S., A simple guide to pot, THC and how much is too much. April 20, 2018, latimes.com, https://www.latimes.com/projects/la-me-weed-101-thc-calculator/
  9. Russo, Ethan. (2008). Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?. Neuro endocrinology letters. 29. 192-200. 10.1522/cla.roj.let. https://www.researchgate.net/publication/5448843_Clinical_Endocannabinoid_Deficiency_CECD_Can_this_Concept_Explain_Therapeutic_Benefits_of_Cannabis_in_Migraine_Fibromyalgia_Irritable_Bowel_Syndrome_and_other_Treatment-Resistant_Conditions
  10. M. Bujalska, H. Makulska-Nowak, S.W. Gumuka,  Magnesium ions and opioid agonists in vincristine-induced neuropathy, Pharmacol Rep. 2009 Nov-Dec;61(6):1096-104. http://www.ncbi.nlm.nih.gov/pubmed/20081245
  11. Onaivi ES, Chaudhuri G, Abaci AS, Parker M, Manier DH, Martin PR, Hubbard JR. Expression of cannabinoid receptors and their gene transcripts in human blood cells. Prog Neuropsychopharmacol Biol Psychiatry. 1999 Aug;23(6):1063-77. doi: 10.1016/s0278-5846(99)00052-4. PMID: 10621950 https://www.researchgate.net/publication/12692236_Expression_of_cannabinoid_receptors_and_their_gene_transcripts_in_human_blood_cells
  12. Erukainure OL, Matsabisa MG, Salau VF, Islam MS. Tetrahydrocannabinol-Rich Extracts From Cannabis Sativa L. Improve Glucose Consumption and Modulate Metabolic Complications Linked to Neurodegenerative Diseases in Isolated Rat Brains. Front Pharmacol. 2020;11:592981. Published 2020 Nov 24. doi:10.3389/fphar.2020.592981 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774498/
  13. Vitamin D and your health: Breaking old rules, raising new hopes. Updated May 17, 2019, Published Feb. 2007, health.harvard.edu, https://www.health.harvard.edu/staying-healthy/vitamin-d-and-your-health-breaking-old-rules-raising-new-hopes
  14. Wróbel A, Serefko A, Szopa A, Ulrich D, Poleszak E, Rechberger T. O-1602, an Agonist of Atypical Cannabinoid Receptors GPR55, Reverses the Symptoms of Depression and Detrusor Overactivity in Rats Subjected to Corticosterone Treatment. Front Pharmacol. 2020;11:1002. Published 2020 Jul 8. doi:10.3389/fphar.2020.01002 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360849/
  15. Image/ Figure “General structure of phospholipids and common head groups.” source: Membrane lipids in Agrobacterium tumefaciens: Biosynthetic pathways and importance for pathogenesis researchgate.net, https://www.researchgate.net/figure/General-structure-of-phospholipids-and-common-head-groups-PLs-contain-two-fatty-acids_fig1_261605192
  16. Hungund BL, Vinod KY, Kassir SA,, et al., Upregulation of CB1 receptors and agonist-stimulated [35S]GTPS binding in the prefrontal cortex of depressed suicide victims. March 2004, Mol Psychiatry 9(2):184-90 DOI: 10.1038/sj.mp.4001376 https://www.researchgate.net/publication/8692237_Upregulation_of_CB1_receptors_and_agonist-stimulated_35SGTPS_binding_in_the_prefrontal_cortex_of_depressed_suicide_victims
  17. Navarrete Francisco, García-Gutiérrez María Salud, Jurado-Barba Rosa, et al., Endocannabinoid System Components as Potential Biomarkers in Psychiatry. Frontiers in Psychiatry Vol 11, 2020, 31 pp, DOI=10.3389/fpsyt.2020.00315 https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00315/full
  18. Li R, Li Y, Liang X, Yang L, Su M, Lai KP. Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets [published online ahead of print, 2020 Nov 10]. Brief Bioinform. 2020;bbaa300. doi:10.1093/bib/bbaa300 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717147/
  19. Lysophosphatidylethanolamine, sciencedirect.com, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/lysophosphatidylethanolamine
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Phospholipids and infant formula

In the last post I stated my long term goal regarding phospholipids and infant or adult complete diet formulas in simplified terms. The primary complicating factor is the limits that are placed on cannabinoids by the U.S. rating of cannabis/marijuana as a plant with no medical value. As a Schedule 1 controlled substance research is only allowed to be performed regarding toxic or addictive aspects of the plant or substance. Many groups including physician groups have stated that the underlying premise that there is no medical value for cannabis/marijuana is wrong. Phospholipids form one part of the more complex group of molecules called cannabinoids and cannabinoids are found in every cell of the body and in most species of animals and many plants and even a few types of insects. The group of chemicals form a flexible part of cell membranes and also act as messenger chemicals that are important in immunity, appetite control and mood to name a few roles. For infants the nutrients are found in a well nourished woman’s breast milk and it helps promote a good appetite and weight gain for the baby. A chronically ill, elderly, or genetically not average person might also need a dietary source of phospholipids or cannabinoids.

So having a goal of establishing an additional ingredient for infant or adult formula is simplifying the need to have the same group of molecules stated to be of medical value within the controlled substance regulations of the U.S. and other countries. Mexico has changed regulations to state medical value so advances in infant and adult formulas with research to show safety and effectiveness might start there unless or until the U.S. companies work with the simpler phospholipids or the Schedule 1 regulation is changed for cannabis/marijuana at the Federal level.

Disclosure: This information is being 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 care guidance. Please seek an individual health care provider for individualized health care guidance.

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Foods that are good sources of phospholipids or other phospho-nutrients

This is not a list of all foods but a list of some good sources mentioned recently and a few additions.

  • Artemisia turanica (wormwood) an herb I take as a supplement I had forgotten that my new bottle uses the botanical name.
  • Amaranth Seed – a grain that can be cooked as a breakfast porridge like dish or is available as a flour. It is gluten free.
  • Asparagus stems
  • Avocado, the fruit, or the inner kernel which can be dried and ground into a powder to use in baking perhaps, I haven’t seen the recipe and having tried to cut one it doesn’t seem like an easy task for the average home kitchen equipment.
  • Beans, common green beans, Adzuki beans, Lentils, Lima Beans, Mung Beans, Green Peas, Split Peas – probably all the bean family.
  • Cardamom – a seed pod available whole or powdered and is generally used as a powdered spice in baked goods or in savory dishes in India style curries.
  • Carrots
  • Cashew nuts, Peanuts, Walnuts, – probably all the nuts, seeds, beans, peas and legumes.
  • Celery stems and leaves
  • Coconut
  • Cumin seed – generally available as a powdered spice and used in bean dishes in Mexican or Indian cooking.
  • Gingko Leaf, available as an herbal supplement called Gingko biloba
  • Grapefruit juice and orange juice.
  • Hemp Seed, Fennel Seed, Flax seed, Squash Seed, Pine Seeds, Pumpkin Seed kernel.
  • Butternut squash and pumpkin.
  • Jerusalem Artichoke (this is a root, not an artichoke, but artichokes are probably a source to as a green leafy type vegetable)
  • Lettuce Leaf, Spinach leaves, Mustard leaves, – many leafy green vegetables.
  • Oats, – most grains like the bean, nut, seed group contain some as phospho-nutrients are part of membranes.
  • Okra seeds (eaten as a green vegetable with the seeds left in the vegetable)
  • Onion root, Garlic, Leek leaves
  • Parsnip root,
  • Pomegranate seeds
  • Rice, white or brown, the bran contains more though.
  • Sesame Seeds (also available as tahini, a sesame paste that is oilier than peanut butter but can be used similarly if used in less quantity)..
  • Sorghum, a grain available whole or as a flour
  • Sweet Potato or Yams
  • Buckwheat, a grain that is not wheat and is gluten free, available as a grain or flour
  • Wheat – a grain typically used a flour but also available in whole wheatberries or cracked wheat or more refined breakfast cereal versions.

Source: Table 4.15 and Table 8.2 Chemistry of Plant Phosphorus Compounds, by Arlen Frank, (1)

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. 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 (1)

 

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It is not a coincidence that my phospholipid rich diet overlaps with the 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.” (7)

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)