Tag: magnesium

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Helping others is a way of life; TRP channels

“Whenever we see something which could be done to bring benefit to others, no matter how small, then we should do it.” — Tai Situ Rinpoche

(SamyeLing.org)

Sometimes getting started is the hardest part.

Notes & links for TRP channel enthusiasts, on chronic pain, gender differences with migraine, IBS/colitis, and the role of magnesium and TRP channels in fetal development:

The condensed version – women are more prone to migraines then men possibly due to a protective effective of testosterone. Estrogen may increase or decrease risk of migraine depending on amounts/balance with progesterone. Either way, magnesium deficiency can increase chronic pain and other TRP channel problems because it is a mineral that helps keep them closed – they are like gates in the cell membrane.

Magnesium deficiency in very early stages of pregnancy or conception can have a negative impact on development of the embryo which can cause problems with physical and/or brain growth which can affect the infant throughout life. Pumpkin seeds has been the short answer I’ve given for years (post) – they are a good source of magnesium and many other nutrients, about one to two ounces, 2-4 tablespoons per day is a healthy serving. Like many things in life too much regularly may not be as healthy. Epsom salt baths are a topical source of magnesium and sulfate which would bypass any problems with digestion making it a good source for people with Irritable Bowel Syndrome or colitis, both of which can be problems linked to overactive TRP channels. (More about magnesium sources.)

Stress can be a cause of overactive TRP channels in addition to the risk of changes occurring during early conception/embryological development.

Other triggers for TRP channels include hot pepper (capsaicin), vitamin D/ and curcumin (a vitamin D analog) a phytonutrient found in turmeric, the yellow spice used in curry powder, ginger, horseradish; volatile chemicals such as formaldehyde, gasoline fumes, cigarette smoke, ammonia; very cold temperatures or very hot temperatures; increased pressure such as might occur during carnival rides or from overeating a large meal or gassy meals with large servings of raw vegetables such as cabbage or broccoli. Cinnamon, mint, vanilla can also activate some types of TRP channels – there is a large variety of TRP channels and they don’t all react to the same triggers and not all types are found in the same organ systems within the body so migraines and bowel troubles may not share the same triggers, but having a place to start can be helpful instead of feeling that everything you eat or do might be a problem.

Interesting hot pepper trivia: “Although both sexes showed sensitivity to capsaicin, males required a four-fold higher dose of capsaicin than females for a similar response (Lu et al., 2009)” (ref 2)

Quotes from an excerpt of ref 1,
(https://www.researchgate.net/figure/Involvement-of-TRP-channels-in-stress-TRPV1-a-member-of-TRP-channel-is-present-in_fig2_234019431) )
Importance of TRP channels in pain:

  • Implications for stress, causal or strong correlation: “altered expression, function and/or regulation of TRPs are key changes which induce patho-physiological conditions like stress, neuropathic pain and cancer.”  
  • “TRPM2 and TRPV4 are involved in oxidative stress- induced cell death of hippocampal neurons (121).” – the hippocampus is an area involved in short term memory and is damaged early in Alzheimer’s disease.
  • “several TRPs can also be activated by estrogen, endrogen, testosterone, cortisol and many other steroids (Table 1)”– so stress could increase TRP channel activity due to inc levels of cortisol. /Speculation: Estrogen mimetics might also be over activating TRP channels./
  • Overactivating TRP channels can also cause IBS symptoms: “over-stimulation of TRPs leads to an influx of excess Ca 2+ which is generally associated with the cell death (126)”
  • “TRPV1 regulates food absorption, emesis, colitis and also regulates the gut – brain axis mainly by responding to endovanilloids and endocannabinoids (132-133).” – colitis is a more severe bowel condition than IBS, has similarities in symptoms though

Re reference 2:
Migraines are 3 times more likely to be a problem for women than men and it may be due to the sex hormone’s ability to activate TRPV1 channels https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102492/ … this info may help with developing more targeted treatments.
“migraineur women exhibited a thicker posterior insula and precuneus cortices compared to male migraineurs & the healthy controls of both sexes (Maleki et al., 2012)”
Testosterone may help protect men from migraines or as severe a migraine if they do have one. It helps modulate activity of TRPM8 channels. Over expression of TRPM8 channels “by a testosterone-mediated mechanism” is seen in prostate cancer.

Re reference 3:
Genetic differences in gene for TRPM8 channels (transient receptor potential melastatin 8) have been identified that are more common in people w migraine sensitivity. They are activated by cold temperatures and/or menthol (mint).

Re reference 4:
TRPM6 & TRPM7 channels and magnesium are known to be critical in embryological development, inc pigmentation/melanin. Mg deficiency during pregnancy can cause significant problems.
TRPM7 & magnesium also critical for dopaminergic cells/Parkinson’s disease. other embryo dev differences w Mg deficiency were seen in the gut & spine (less straight). – a review: TRPM Channels and Magnesium in Early Embryonic Development (4)

TRP channels may become overly active from stress or during fetal development. The symptoms can be difficult to notice a pattern of triggers because the TRP channels have many different ways of being activated. See the G3 excerpt in this document for more details, Child Trauma, Possible Relationship or Chronic Physical Symptoms as an Adult – or for a more condensed version see the graphic below.


“If I had more time, I would have written a shorter letter.” ~ Blaise Pascal

(QuoteInvestigator)
Things that may overstimulate TRP channels.

“Well begun is half done.” – Aristotle

Disclaimer: This information is provided for educational purposes within the guidelines of fair use. It is not intended to provide individual health care guidance. Please seek a health care professional for individualized health care guidance.

References:

  1. Kumar, Ashutosh & Goswami, Luna & Goswami, Chandan. (2013). Importance of TRP channels in pain: Implications for stress. Frontiers in bioscience (Scholar edition). S5. 19-38. https://www.researchgate.net/publication/234019431_Importance_of_TRP_channels_in_pain_Implications_for_stress
  2. Artero-Morales M, González-Rodríguez S, Ferrer-Montiel A. TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain. Front Mol Biosci. 2018;5:73. Published 2018 Aug 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102492/doi:10.3389/fmolb.2018.00073 Interesting hot pepper trivia: “Although both sexes showed sensitivity to capsaicin, males required a four-fold higher dose of capsaicin than females for a similar response (Lu et al., 2009)”
  3. Dussor G, Cao YQ. TRPM8 and Migraine. Headache. 2016;56(9):1406-1417. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335856/
  4. Komiya Y, Runnels LW. TRPM channels and magnesium in early embryonic development. Int J Dev Biol. 2015;59(7-9):281-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685952/

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Fonia- sustainable grain

Our changing world and growing population can benefit from changing what we put on our menu plans – change what we eat often. Fonia is a drought tolerant grain in the millet family which can be harvested in just six to eight weeks from planting and it tolerates poor soil conditions.

Fonia is native to West African countries and may also have been used by ancient Egyptian cultures as the grain has been found in archeological sites.

Fonia is cooked similarly to rice but is a smaller grain. It would be good as a hot breakfast porridge or used like rice in salads or side dishes. It is gluten free, rich in fiber, protein, magnesium, zinc, and B vitamins. For more information and a couple recipes see: “Whole Grains- Fonio,” By Jessica Levinson, Today’s Dietitian, https://www.todaysdietitian.com/newarchives/0918p12.shtml

Disclaimer: Information provided for educational purposes within the guidelines of fair use, not intended for individual health care guidance.

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High blood pressure and possible ethnic differences

On page 66 of a new book Plagues and the Paradox of Progress: Why the World is Getting Healthier in Worrisome Ways, by Thomas Bollyky, it is mentioned that early Western medical personal working in Africa in the 1920s were surprised to find no cases of hypertension/high blood pressure among the native African people. Only one native woman was known to be overweight and it was noted that she worked in a brewery which led the medical person in the document to speculate whether beer drinking could be fattening (yes it can). The first case of hypertension in a native African person wasn’t noted until the 1940s.

Question: Does the Western style of living or working or export of Western products cause hypertension in native Africans? If native Africans living in their traditional environment using their traditional diet have no risk for hypertension then what changed that caused an increased risk? This topic is also important for prenatal health as preeclampsia can include hypertension/high blood pressure and it does tend to be an increased risk for women with African American ancestry. The DASH diet may be helpful, for more on preeclampsia risk factors and possible tips for prevention or management, see Preeclampsia & TRP Channels, effectivecare.info. 

Dr. Agbai’s discovery that helps protect against symptoms of Sickle Cell Anemia – Thiocyanate.

Yes per Dr Agbai who has worked with patients in Africa and in the U.S., the standard diets are different. There is a difference in type of starch and amount of starch in typical African or Jamaican diet and western U.S. style diet, and there is a difference in amounts of foods that contain thiocyanate. The yams commonly grown in Africa are larger and woodier/less sweet than sweet potatoes and they are also a good source of thiocyanate.

Thiocyanate is a phytonutrient that helps protect against Sickle cell anemia by preventing the red blood cells from forming the sickle shape instead of the normal round indented shape (like a tire or doughnut shape that has a filled in shallower center). It is important to eat adequate iodine and protein rich foods that contain methionine (found more in animal product protein sources than in a vegan diet) in order to protect thyroid health.

Listen to interviews with Dr. Agbai by the radio show Your Own Health and Fitness: http://www.yourownhealthandfitness.org/?page_id=509

Agbai O. Anti-sickling effect of dietary thiocyanate in prophylactic control of sickle cell anemia. J Natl Med Assoc. 1986;78(11):1053-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571427/

There may be a slight difference in retention of calcium and loss of magnesium that would be protective with a diet low in calcium might may increase risk of metabolic syndrome type conditions when excess calcium.

I’ve discussed this topic of potential differences between western style diet and traditional African culture and possible differences in health in my early days of blogging when I found a research article from ~ 1970s that noted ethnic differences in health outcomes but did not take into account possible differences in average ethnic diet at the time. (I haven’t found that article in my files yet. I will update this post if I do find it.) To get to the point directly – people with native African ancestry may have kidney differences that conserve calcium better, and possibly not conserve as much magnesium, as other ethnic groups. This would be protective when calcium was not very available in the diet but then would be an increased negative health risk if the diet contained a lot of calcium or phosphorus.

There is known problems in medical research in the U.S. with bias in research studies towards use of white males as study participants with less information gathered about minority groups and females.

Before discussing calcium and magnesium and kidney health in more detail – briefly – there is bias in medical research towards white males. Research studies over the years have often had more limited numbers of minorities and females among the experimental and control groups or as a focus of research. A summary of the issue was included in a recent article in the New York Times that is focused on the potential benefits and risk of bias in the use of Artificial Intelligence (AI) in medical diagnostic processes or other medical roles.

” Medicine has long struggled to include enough women and minorities in research, despite knowing they have different risk factors for and manifestations of disease. Many genetic studies suffer from a dearth of black patients, leading to erroneous conclusions. Women often experience different symptoms when having a heart attack, causing delays in treatment. Perhaps the most widely used cardiovascular risk score, developed using data from mostly white patients, can be less precise for minorities. ” – Dhruv Khullar

“A.I. Could Worsen Health Disparities,” by Dhruv Khullar, The New York Times, Opinion, Jan. 31, 2019

It is not racist or sexist to discuss differences in physiology and the potential effects those differences might have on health. It is discriminatory to only study one group of people primarily and then try to treat everyone else as if they weren’t individuals but were all instead exactly like the group that had been studied. It is discrimination to not treat individuals as individuals or to pretend that differences don’t exist.

Adequate magnesium is needed for preventing high blood pressure, cardiovascular disease, and many other chronic conditions including dementia.

Low magnesium levels, particularly when there is also plenty of phosphorus may increase cardiovascular risks. Adequate magnesium levels are protective and elevated magnesium is unusual and may be increase cardiovascular risks. In good health the body maintains magnesium and other electrolyte levels within specific ranges. (5) Higher magnesium levels have also been associated with higher levels of potassium and of albumin, a blood plasma protein, (6), which is important for fluid balance and transport of a variety of chemicals in addition to magnesium (such as steroids, fatty acids, and thyroid hormones (wikipedia/serum albumin), about 30% of serum magnesium is carried in a non-electrically active form on proteins, primarily albumin (Clinical Biochemistry/serum magnesium) (9).

Alzheimer’s dementia and other types of dementia are more common in blacks than whites in the U.S. and may be a risk earlier in life too, early onset Alzheimer’s can occur in the forties and fifties instead of the more frequent age of diagnosis after age 60. See: African Americans Face Greater Risk of Alzheimer’s Disease than Whites, usatoday.. The reason is not known but the increased frequency on high blood pressure in blacks is thought to be a risk factor.

There may be differences in rate of urinary loss of albumin in different ethnic groups. With the presence of excess abdominal weight participants in a renal study of Hindustani-Surinamese, or African-Surinamese ancestry had an increased likelihood of albuminuria than participants of Dutch ancestry with the greatest risk found in the Hindustani-Surinamese group. (7) Asian Americans and African Americans were found to have better blood albumin levels in a renal study and the Asian Americans had better renal biomarkers compared to other ethnic groups in the study. (8)

When looking at hypertension and high blood pressure risk with the same diet in modern research there is a significant increased risk for African Americans to have high blood pressure and to have it occur earlier in life than in whites. (prevalence in the U.S. of hypertension in adults was “42 % for blacks and 28 % for whites,” (2011-2012)). (2)

So it is a good question – how did hypertension frequency in Africans in the 1920s change from zero to 42% for African Americans in the United States, in 2011-2012? Diet differences that were noted in 2009-2010 between white groups and African American groups were more cholesterol and sugar and less fiber, whole grains, nuts/beans/seeds, fruits and vegetables for the African Americans on average. Dairy intake was not mentioned as being significantly difference. In another research comparison calcium intake was lower on average in African Americans but so was magnesium (Table 1). (2)

Within the introduction and Diet and Blood Pressure sections of the article it is mentioned that ethnic differences in cardiovascular metabolism has been noted in African American groups and that their reduction in blood pressure when following the DASH diet was even better than the reduction in people of other ethnic background who followed the diet (it includes a magnesium rich Beans/Nuts/Seeds group as a daily/weekly recommendation). The INTERMAP study found an increased Sodium to Potassium ratio in urinary excretion and less total Potassium urinary excretion for the African American participants than white participants. (2)

Other research has also supported the idea that high blood pressure may have more to do with excess sodium (salt) intake in relation to low potassium intake than just having to do with the amount of sodium in the diet. Potassium is found in all vegetables and fruits in varying amounts, beans/nuts/seeds, and in liquid milk and yogurt. (Kidney dialysis and other patients with Chronic Kidney Disease have to avoid excess potassium so this article includes a list of potassium rich foods for the purpose of educating regarding what needs to be limited but for people of average kidney health it is a list of good sources to include in the diet: Potassium and Your CKD Diet, National Kidney Foundation.

Learning is an ongoing process, in the meantime some possible health tips for people of any ancestry:

  1. Adequate magnesium is essential for kidney and heart health and high blood pressure is an early symptom of low magnesium levels. Dietary sources may not be sufficient if intestinal absorption is poor or if renal losses are excessive. Epsom salt baths or footsoaks or magnesium chloride are topical forms. Adequate protein and phospholipids in the diet are also important to provide the albumin and other specialized transport molecules that carry magnesium and other chemicals within the vascular or other fluids of body tissue. More information about magnesium sources and symptoms of deficiency are available in a previous post: To have optimal Magnesium needs Protein and Phospholipids too.
  2. Adequate calcium and vitamin D are needed for health however excess may cause an imbalance between calcium and magnesium levels as magnesium is excreted along with excess calcium by the kidneys and less magnesium may be absorbed by the intestines as vitamin D causes increased absorption of calcium and magnesium but calcium may be more available in a modern processed food diet. For more information about vitamin D sources see: Light up your life with Vitamin D, peace-is-happy.org. Deficiency of calcium or of vitamin D can cause secondary hyperparathyroidism which can also be more common in renal failure due to excess phosphorus buildup and deficiency of active vitamin D. The healthy kidney is involved in activating vitamin D. (Secondary hyperparathyroidism, National Kidney Foundation) Calcium is plentiful in most dairy products and is also found in almonds, sesame seeds, beans, dark green leafy vegetables and other produce. Variations of a 2000 calorie menu plan shows that even a vegan diet can provide 1000 milligrams of calcium per day and a menu with dairy products can provide an excess with over 1600 milligrams of calcium, see: Healthy Hair is the Proof-of a healing diet.
  3. The DASH diet (Dietary Approach to Stop Hypertension) may help because it encourages potassium and magnesium rich vegetables, fruits, beans, nuts and seeds. Calcium is provided without being over recommended with two to three servings of dairy group foods. See example daily/weekly diet plan recommendations here: What is the DASH diet?, dashdiet.org.
  4. Adequate without excess protein helps protect the kidneys from having to overwork excreting nitrogen from excess protein breakdown. Adequate water is essential for kidney and vascular health as it helps with excretion of toxins and transport of nutrients and oxygen in the vascular system. More information about protein and water recommendations are available in a previous post: Make every day Kidney Appreciation Day.

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

  1. Thomas Bollyky, Plagues and the Paradox of Progress: Why the World is Getting Healthier in Worrisome Ways, 2018, MIT Press, https://mitpress.mit.edu/books/plagues-and-paradox-progress
  2. Chan Q, Stamler J, Elliott P. Dietary factors and higher blood pressure in African-Americans. Curr Hypertens Rep. 2015;17(2):10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315875/“Marked ethnic differences exist in bone metabolism and development of calcified atherosclerotic plaque (CP). Relative to European-Americans, African-Americans have lower rates of osteoporosis (despite ingesting less dietary calcium), form fewer calcium-containing kidney stones and manifest skeletal resistance to PTH (1,2,3). Systemic differences in regulation of calcium and phosphorus appear to be involved (4). Related phenomena may include the markedly lower amounts of calcified CP in African-Americans, despite the presence of more severe conventional cardiovascular disease risk factors (5,6,7,8,9). Together these observations suggest biologically mediated ethnic differences in the regulation of bone and vascular health.” […]  “The DASH/DASH-Na diet BP reduction was more pronounced for blacks compared to whites [31, 36, 37]. Although the DASH dietary approach has been incorporated into lifestyle changes recommended for patients with HTN [3], data show that few hypertensive Americans consume diets even modestly concordant with the DASH diet and less so for blacks [38]. Only about 19 % of individuals with known HTN from NHANES 1999–2004 had DASH-concordant diets.”
  3. Barry I. Freedman, et al, Vitamin D, Adiposity, and Calcified Atherosclerotic Plaque in African-Americans,J Clin Endocrinol Metab. 2010 March; 95(3): 1076–1083. [ncbi.nlm.nih.gov/pmc/articles/PMC2841532/?tool=pubmed]  
  4. Potassium and Your CKD Diet, National Kidney Foundation, https://www.kidney.org/atoz/content/potassium
  5. Ryota Ikee, Cardiovascular disease, mortality, and magnesium in chronic kidney disease: growing interest in magnesium-related interventions, Renal Replacement Therapy, 2018 4:1,   https://rrtjournal.biomedcentral.com/articles/10.1186/s41100-017-0142-7
  6. Noriaki Kurita, Tadao Akizawa, Masafumi Fukagawa, Yoshihiro Onishi, Kiyoshi Kurokawa, Shunichi Fukuhara; Contribution of dysregulated serum magnesium to mortality in hemodialysis patients with secondary hyperparathyroidism: a 3-year cohort study, Clinical Kidney Journal, Volume 8, Issue 6, 1 December 2015, Pages 744–752, https://doi.org/10.1093/ckj/sfv097
  7. van Valkengoed IG, Agyemang C, Krediet RT, Stronks K. Ethnic differences in the association between waist-to-height ratio and albumin-creatinine ratio: the observational SUNSET study. BMC Nephrol. 2012;13:26. Published 2012 May 7. doi:10.1186/1471-2369-13-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492102/
  8. Frankenfield DL, et al., Differences in intermediate outcomes for Asian and non-Asian adult hemodialysis patients in the United States, Kidney International, Vol 64, Issue 2, Aug. 2003, pp 623-631 https://www.sciencedirect.com/science/article/pii/S0085253815493706
  9. M H Kroll, R J Elin, Relationships between magnesium and protein concentrations in serum. Clinical Chemistry Feb 1985, 31 (2) 244-246; http://clinchem.aaccjnls.org/content/31/2/244.long
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Pumpkin seeds – rich in zinc

Pumpkin seed kernels, raw, unsalted.

Pumpkin seed kernels are a good source of protein, essential fats, fiber, magnesium and other vitamins and minerals – and a great source of zinc which may be lacking in vegetarian or vegan diets. (Pumpkin Seeds – Benefits, nutrition and dietary tips.) (Other vegetarian sources of zinc.)

Work is progressing on the development of pumpkin seed flour for use as a food thickening substance for use in gravies or other sauces or stews. It would increase the protein, essential fatty acids, and other trace nutrient content of the resulting foods. (10) The use of pumpkin seeds in the diet may also prove to be protective against cancer and liver or kidney injury; and as a good source of antioxidants such as carotenoids (vitamin A family of nutrients) the use of pumpkin seeds in the diet may prove to be helpful against many conditions that involve excess oxidative stress. (4, 5, 6, 7, 8, 9) They are also a source of vitamin E (tocopherols), other phytosterols, and linoleic acid, a beneficial polyunsaturated fat. Pumpkin seed oil may be helpful in wound healing. (15) Pumpkin seeds are also a good source of phospholipids, (16), which are important for skin and membrane health.

Pumpkins are considered a drought tolerant plant for gardeners. Adequate water is needed to grow larger pumpkin and squash but the vines can survive limited water conditions. The seeds of other summer and winter squash are also nutrient rich and also may be more drought tolerant plants. (11, 12) Enough but not too much water at the right times are critical. Flooding or severe drought may both harm the garden yield. Mulching and drip irrigation or other watering methods applied at optimal stages of growth can be the water thrifty solution for best yield. (13, 14)

The seeds of butternut squash and some types of winter squash can be collected when trimming the squash and later toasted and eaten as a crunchy nutritious snack. India grocery markets may also have shelled squash seeds available for sale. They are slightly smaller and paler in color than the shelled pumpkin kernels in the image above.

Magnesium is one of the beneficial nutrients found in pumpkin seeds. It is a mineral that is needed in greater quantity during pregnancy and high blood pressure/hypertension can be a symptom of deficiency. Preeclampsia and the more severe eclampsia are complications characterized by high blood pressure and edema/swelling that can occur during pregnancy. Toxins collect in the excess fluid buildup and can risk a brain condition similar to hypertension encephalopathy in the more severe eclampsia. Seizure activity can result and death for the woman and expected infant are risks. Magnesium is used as an intravenous or intramuscular injection to reduce risk of the seizures during eclampsia. The mineral seems to help protect the blood brain barrier and reduce swelling in the brain during eclampsia. It’s role as an antioxidant to reduce free radical toxins may be involved but the exact mechanism for its benefit in eclampsia is not known. (2, page 139)

More information about preclampsia is available in a previous post, and more information about food sources and supplement sources of magnesium is also available in a previous post.

I have several writing projects in draft mode however they overlap – pumpkin seeds, a good source of magnesium and zinc, helped my previous prenatal clients who had a history of preeclampsia or high blood pressure in a previous pregnancy prevent a reocurrence of the problem. Why? Possibly because of the magnesium and other beneficial nutrients which could be protecting the blood brain barrier and might then also be helpful for preventing harm to oligodendrocytes and protect against demyelination – a risk that can occur with some types of encephalopathy (3).

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

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827242/Megan Ware, What are the health benefits of pumpkin seeds?, July 24, 2018, https://www.medicalnewstoday.com/articles/303864.php
  2. Mehmet Kaya, Bulent Ahishali, Chapter 9: The role of magnesium in edema and blood brain barrier disruption, page 139, in the book edited by Robert Vink, Mihai Nechifor, Magnesium in the Central Nervous System, University of Adelaide Press, 2011, adelaide.edu.au, free ebook pdf, https://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf  (2) 
  3. S. Love, Demyelinating Diseases, J Clin Pathol. 2006 Nov; 59(11): 1151–1159.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860500/ (3)
  4. Scientific Studies collection on a commercial website by Pepo Farms, https://pepofarms.com.au/scientificstudies/ (4) which includes:
  5. M. Gossell-Williams, A. Davis, N. O’Connor, Inhibition of Testosterone-Induced Hyperplasia of the Prostate of Sprague-Dawley Rats by Pumpkin Seed Oil. Jun 2006, Vol. 9, No. 2 : 284 -286. 
  6. C. Z. Nkosi, A. R. Opoku, S. E. Terblanche, Antioxidative effects of pumpkin seed (Cucurbita pepo) protein isolate in CCl4-Induced liver injury in low-protein fed rats.
  7. Fahim AT Abd-el Fattah AA Agha AM Gad MZ
    Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats.
    In: Pharmacol Res (1995 Jan) 31(1):73-9 ISSN: 1043-6618
  8. Suphakarn VS Yarnnon C Ngunboonsri P, The effect of pumpkin seeds on oxalcrystalluria and urinary compositions of children in hyperendemic area. In: Am J Clin Nutr (1987 Jan) 45(1):115-21 ISSN: 0002-9165
  9. Matus Z Molnar P Szabo LG [Main carotenoids in pressed seeds (Cucurbitae semen) of oil pumpkin (Cucurbita pepo convar. pepo var. styriaca)] Olajtok (Cucurbita pepo convar. pepo var. styriaca) magjabol nyert presmaradek ossz-karotinoid-tartalmanak es karotinoid-osszetetelenek meghatarozasa. In: Acta Pharm Hung (1993 Sep) 63(5):247-56 ISSN: 0001-6659 (Published in Hungarian)  * The main carotenoids included per the Pepo Farms site: “The main components of the press-residue were lutein [3,3′-dihydroxy-alpha-carotene = (3R,3’R,6’R)-beta,epsilon-carotene-3,3′-diol; 52.5%] and beta- carotene (beta,epsilon-carotene; 10.1%). In addition to the above- mentioned pigments it was successful to reveal the presence of violaxanthin, luteoxanthin, auroxanthin epimers, lutein epoxide, flavoxanthin, chrysanthemaxanthin, 9(9′)-cis-lutein, 13(13′)-cis- lutein, 15-cis-lutein (central-cis)-lutein, alpha-cryptoxanthin, beta- cryptoxanthin and alpha-carotene (beta,epsilon-carotene) in small quantities.”  (4)
  10. Initial food technology research on the preparation and use of pumpkin seed flour for use in more nutritious gravy type sauces: Sharma G, Lakhawat S., Development, Quality Evaluation and Acceptability of Pumpkin Seed Flour Incorporated in Gravy. J Nutr Food Sci 7:613. doi: 10.4172/2155-9600.1000613      https://www.omicsonline.org/open-access/development-quality-evaluation-and-acceptability-of-pumpkin-seed-flourincorporated-in-gravy-2155-9600-1000613.php?aid=91345
  11. EllenB, Growing Drought Tolerant Vegetables, June 9, 2009, ThriftyFun.com, https://www.thriftyfun.com/Growing-Drought-Tolerant-Vegetables.html (11)
  12. Troy Scott, Drought Tolerant Vegetables for your Garden, July 9 2018, HeavenlyGreens.com http://www.heavenlygreens.com/blog/drought-tolerant-vegetables-for-your-garden (12)
  13. Joan Morris, Vegetable Gardening in a Drought, mercurynews.com, April 1, 2015,  https://www.mercurynews.com/2015/04/01/vegetable-gardening-in-a-drought/ (13)
  14. Extension Utah State University, Vegetable Irrigation: Squash and Pumpkin, Horticulture/Vegetables/2015-4,   https://digitalcommons.usu.edu/cgi/viewcontent.cgi?article=1744&context=extension_curall (14)
  15. Bardaa S, Ben Halima N, Aloui F, et al. Oil from pumpkin (Cucurbita pepo L.) seeds: evaluation of its functional properties on wound healing in rats. Lipids in Health and Disease. 2016;15:73. doi:10.1186/s12944-016-0237-0. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827242/ (15)
  16. Zh.Y. Petkova, G.A. Antova, Changes in the composition of pumpkin seeds (Cucurbita moschata) during development and maturation. Grassas Y Aceites, 66 (1), Jan–March 2015, e058. http://grasasyaceites.revistas.csic.es/index.php/grasasyaceites/article/viewFile/1523/1658 (16)