Frog ponds, evolution, embryology, and topical magnesium; Magnesium Part 4 by DoorlessCarp.

also, reMag, a liquid magnesium product by Carolyn Dean, MD

We have had so many generations of chronic nutrient deficiency in the US that “Mom knows best/Grandma knows best” became lost — great, great, great grandma might have known but now we don’t remember what health used to be like.

After becoming replete in iodine at around age 40ish, my body gained function that it had never had → how could I have known what I was missing out on if I never had taken high dose iodine? With multi-generational lack in iodine, how could my mother have told me something she didn’t know? (*different topic > different post)

Magnesium deficiency can look like: Migraines every week for years, tinnitus, eyelid twitching - a mini muscle cramp, muscle cramps, pain, puffiness, and tearful or cranky moods. How do you know that is not normal if it is happening daily?

• Magnesium deficiency symptoms are detailed in Table 1: (Gröber, et al., 2017)

I needed topical sources of magnesium though, within 20 minutes of a magnesium salt bath, my bad mood and muscle cramps can be improved.

Chelated forms of magnesium for dietary supplements are more expensive but are better tolerated than ionic magnesium oxide. Mg oxide is the dietary supplement most likely to cause watery stools as a negative side effect, which is not pleasant but it is not a toxic effect. It is a fluid shift caused by an excess of ionic magnesium in the intestines.

In evolution, we seem to have developed with an expectation for magnesium to be in our bathing and drinking water, because in nature it is - generally. Our kidneys and intestines are set up to absorb and save calcium, because in the diet and nature, calcium is fairly rare - eat the tiny bird egg, shell and all. Eat the tiny fish, bones and all. Most or many cultures did not milk cows or goats, as adults often don’t digest lactose well.

Topical absorption of Mg is an old interest of mine. It helped my own chronic migraine problem a lot as a preventive rather than a treatment during a headache. Getting regular soaks led to fewer migraines. In this 2019 post, transcendingsquare, I tried to get interest going in Epsom salt foot soaks for emergency rooms, homeless shelters or nursing homes. From references that I found, magnesium salts are absorbed well through skin pores/hair follicles and around the finger and toenails.

Sulfate from Epsom salt penetrates skin rapidly, suggesting sulfate transporters, magnesium wasn’t readily absorbed in a brief experiment, a longer interaction was tested in a following experiment by Dr. Waring:

“To check this, 2 volunteers wore ‘patches’ where solid MgSO4 was applied directly to the skin and sealed with a waterproof plaster. Plasma/urine analysis confirmed that both Mg and sulfate levels had increased so this is potentially a valuable way of ensuring Epsom salts dosage if bathing is not available. Interestingly, both volunteers, who were > 60 years old, commented without prompting that ‘rheumatic’ pains had disappeared.” (Waring, Epsom Salt Council)

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We may be designed to absorb magnesium in our bathing and drinking water, so the liquid supplement product developed by Carolyn Dean, MD, called reMag, may be better absorbed for the same reason. Small amounts in drinking water is what our gut expects, so there would be no odd signaling, leading to no sudden watery dumping effect from TRP or calcium channels having been overactivated. (Roughly - I’m not sure of the exact details.) The product reMag provides 150 mg of elemental magnesium in 1/2 teaspoon which is supposed to be mixed in a liter of water and drunk “at once or throughout the day” - drinking a liter of water at once is really too much. (rnareset.com/remag-liquid-magnesium) Having two liters with 1 teaspoon would provide 300 mg, closer to the daily goal - but it would be drunk slowly over the whole day. But the dilution point is made, the gut wouldn’t be getting a 250-400 mg load of magnesium at once.

Carolyn Dean’s book on magnesium and magnesium product are discussed and excerpted in Doorless Carp’s Magnesium deficiency and associated pathologies: Part 4 post. The post is mostly focused on supplement types, pros and cons, but it also includes endocrinology - the interplay between magnesium and thyroid hormone and other hormones. The post also has a bonus - two free pdfs of Carolyn Dean’s books on magnesium.

Magnesium deficiency and associated pathologies: Part 4

>> Carp are swimming in magnesium water and drinking tiny amounts of Mg with the river or pond water. Humans evolved in an environment rich in liquid with magnesium. Our intestines and kidneys dump magnesium readily and preferentially absorb calcium which is more scarce in the diet. We evolved in an environment with magnesium rich bathing and drinking water and I think the body expects that environment still.

Logically, to me, if a critically essential nutrient isn't being readily absorbed in the gut from dietary sources, then it must have been available to us through another route. We don't get our daily oxygen from our food intake or gut absorption, maybe we aren't intended to get all of our magnesium through our gut either. Nature doesn't make mistakes. Our food supply isn't what it used to be, but, the kidneys and gut are set up to save calcium and waste magnesium - that logically suggests to me that the body expects to have lots and lots of magnesium and to have less access to calcium. ..... so how could that be true? If we were spending time in magnesium rich water and drinking it also. The gut wouldn't have to handle a crazy high dose amount of magnesium from crushed rock, it would be getting tiny amounts all day long - a very divided dose.

A liquid mineral supplement meant to be added to a quart of water and drunk over the day would be providing a very "divided" dose which the body might be absorbing little bits of all day instead of it causing a TRP channel shift of fluid and 'dumping' like watery stools. Maybe that is what nature expects.

The ridiculously low Tolerable Upper Limit in the US was set with guesstimates and more research was supposed to have been done, AND the only negative, the only risk involved, is the watery stool effect. Which is bad and is dehydrating.

It lasts all day, not just one watery stool after taking a Mg oxide, or staying in the bath too long (can happen). But it is hardly deadly unless you don't understand what is happening and cause yourself daily fluid loss by continuing to take a supplement that isn't being absorbed well and instead is causing a rapid trip to the bathroom with 'watery stool' - which is more descriptive than 'diarrhea'.

The adverse reaction from some magnesium supplements is not the contents of the intestines blasting out, it is body fluid being suddenly dumped into the intestines due to TRP or calcium channels having been opened by the influx of ionic magnesium from the supplement (or from staying too long in the Mg bath). *CK Masterjohn knows more about this.

Magnesium is poorly absorbed for a few reasons, as I understand it, the acidity of the intestines make it difficult for the magnesium ion to not precipitate out instead of staying in an absorbable ionic form. Also vitamin D encourages the intestines to preferentially absorb calcium over magnesium, and the kidneys preferentially hold onto calcium while readily dumping magnesium.

Regarding magnesium baths:

The 20 minute bath is very effective with Epsom salt or Mg chloride for my muscle cramp and mood symptoms. Baths are just so fast and helpful for muscle cramps or pain. It is getting everywhere in the body much faster than a dietary supplement that may or may not be well absorbed.

Cautions with topical Epsom salt or Magnesium chloride baths -

1. Sulfate sensitive folks should use magnesium chloride flakes instead of the more readily available Epsom salt. Whether a person is sulfate sensitive is important to know, because the Epsom salt, Mg sulfate bath can cause symptoms of sulfate excess in a sensitive person, especially if soaking a little longer. That includes a racing heart rate which can feel like a panic attack and it doesn’t slow very soon. Ylang Ylang essential oil can help slow the tachycardia fairly quickly, within 0 minutes if you are also laying calmly and breathing slowly.

2. If the magnesium was becoming excessive, then the heart rate would slow down, bradycardia and muscle relaxation can occur → and diarrhea.

3. . . . So don’t soak too long. Research used 20 minutes for a medicinal bath and soaking about 40 minutes or longer seems to be when I might start having a watery stool side effect day. If your body is more deficient, you can soak longer than when replete before side effects might occur of slowing heart rate and relaxing muscles - including the anal sphincter. » Get out of the bath. Twenty minutes is long enough for my muscle cramps and cranky or tearful mood to improve.

Topical magnesium absorption vs intestinal malabsorption/watery stool reaction.

In the article by Doorless Carp, Carolyn Dean is quoted extensively regarding oral magnesium supplements (she developed a liquid product that works well) - her own health needs required higher dose magnesium but the watery stool side effect that can occur did, limiting absorption of oral supplements - it goes straight through instead of being absorbed.

It is nice that Carolyn Dean was able to devise a formulation of magnesium that is better absorbed as an oral supplement, but topical absorption really can work - but I have to keep it up - every -7 days or I start feeling muscle crampy. (I need one today, I took one on the 23rd). Taking oral supplements just doesn’t seem to prevent the crampy/cry-y/cranky that happens if I put off the magnesium bath.

My problem is similar but a little different - I won’t get watery stools that readily, but oral supplements just don’t seem to do much. I have to have a topical source/bath with Epsom salt or Magnesium chloride every 5 days or so. Otherwise I get muscle cramps and moody anxiety.

What maybe missed or unknown information - is that magnesium ion channels (TRPM 6 and 7) may be dysfunctional in the gut due to a genetic difference. (Walder, et al., 2002) Without magnesium ion channel function, the intestines may not be absorbing much magnesium. Chelated forms may be absorbed differently, as the bound amino acid glycinate perhaps.

Regarding topical magnesium chloride lotions/soaps etc:

Topical magnesium products do not seem that effective or it is quite variable. But that is where a lot of research funding went - towards product development rather than testing absorption from baths.

Regarding topical products, though, I had a tip in my replies about using DMSO in the lotion mix, to increase absorption, and I tried that with Mg Chloride in a coconut based body lotion and it really does seem to help my mother quite a bit. Roughly, about a half teaspoon of DMSO with a tablespoon of Mg chloride dissolved in a tablespoon or two of hot water - mix that into some coconut oil body lotion with a hand blender. And add some essential oil drops too for aromatic and health benefits!

My mother has late stage Alzheimer's and refuses to do baths/hand or foot soaks and doesn't really like body lotion either, but will accept that better than trying to do the hand soaks. We did those for a while. Percentage of body surface and time soaking seems to count - more skin surface is better, providing a bigger dose of magnesium potentially. Can you apply the lotion over most of the body, or just the hands? >> It needs to be over more of the skin pores and hair follicles for better efficacy. A bath is better than a lower leg soak, which is better than a feet-only soak, which is better than a hands-only soak --> my impression. If I have to substitute a foot/leg soak for a bath I soak for 40 minutes/until the bucket of water is cold.

I think genetically my mother and I don't have TRPM ion channel function in our intestines and we really need the topical source over any dietary type of supplement. Lifelong high dose supplementation is the suggested treatment approach to a TRPM6 gene allele causing dysfunction. Poor intestinal absorption is the problem rather than renal loss. (Walder, et al., 2002)

A nephrologist recommends 400 mg elemental magnesium equivalent three times a day for kidney patients who are losing excess magnesium - and are not on dialysis. (Martin, et al., 2009) Magnesium was one of my earliest blogging topics. MARCH 25, 2011 BY JENNY, Hypomagnesemia symptoms and causes list.

Magnesium glycinate kind of helps me, but the baths help a lot more noticeably and are less expensive.

Topical magnesium from an evolutionary perspective - an amphibious perspective.

Our mucous membranes lining our mouth are as absorptive as amphibian skin.

Looking back in time, a long way back — life developed in the oceans and we slowly grew the ability to crawl up on land and breathe the air. Our skin had absorbed everything we needed in the ocean in early stages of simple life, pores formed for better control of nutrients and toxins, and then more complex gills for selectively absorbing some nutrients more than others.

I use the collective “we” to describe this chain of life. In embryology, we can see that we do encompass the chain of life, as the fetus visibly transforms during from a single fertilized cell to a ball of cells to a simple cylindrical form, then to a tadpole like form, then limbs sprout from the tadpole and the tail is taken back up - we are evolution - we are all of the groups in the Kingdom of life at very basic levels.

At a very basic level, at some distant point in the past, we were amphibians before mammals existed.

Within our eyes there are melanin producing cells similar to melanocytes found in frog skin, and the cells help control our circadian cycles. The cells produce a special form of melanin called melanopsin which helps regulate our internal biological clock. Light on the frog skin or light in our eye affects circadian changes in our gene expression - should we have the day time genes be active or the night-time types of genes? The melanopsin cells in the retina are likely projecting up to suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker area of the brain. (Provencio, et al, 2000) (Melanopsin and cryptochromes, Kruse interviews.)

“A new nominee for the elusive photoreceptor is melanopsin. Mark D. Rollag and Ignacio Provencio of the Uniformed Services University of the Health Sciences in Bethesda, Md., and their colleagues originally discovered this member of the opsin family in the skin, eyes, and brains of frogs. In the Jan. 15 Journal of Neuroscience, they report finding the human version of the protein and reveal that melanopsin is made by cells in the eye’s inner retina. In contrast, the eye’s rods and cones are in the outer retina.” - Protein [melanopsin] may help eyes tell time, (sciencenews.org) See: (Provencio, et al, 2000)

Melanopsin expressing cells are found in the same areas of the brain as our circadian controls

“The unique inner retinal localization of melanopsin suggests that it is not involved in image formation but rather may mediate nonvisual photoreceptive tasks, such as the regulation of circadian rhythms and the acute suppression of pineal melatonin. The anatomical distribution of melanopsin-positive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker.” (Provencio, et al, 2000)

Andrew Huberman and Jack Kruse were discussing it and seemed astonished that we have amphibian like parts ~ “We’re not amphibians!” No, we are not currently, but we were amphibians collectively before mammals existed, so the chicken or egg question here is answered - amphibians existed before mammals, therefore mammals are going to be based somewhat on amphibians . . . and prior to that on fish . . . and way earlier . . . on amoeba or other single celled critters.

And amphibians can have a tadpole phase.

And humans do have a tadpole-looking phase in our early fetal development. Not exactly, but a little like tadpole, around four weeks after conception. Convention counts from the last period and that includes two weeks of not having conceived yet.

At four weeks after conception the embryo looks kind of tadpole like. (mayoclinic.org)

• Pregnancy, Week by Week, Mayo Clinic, https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/prenatal-care/art-20045302

Ten weeks after conception the embryo looks like a tiny baby, about 2 and a half inches long, weighing only a half ounce, 14 grams. (mayoclinic.org)

Amphibians would have crawled out of the ocean/lake, prior to mammals. Exactly how that occurred is debatable (This guy is debating the current theories about how fish evolved into amphibians, digitalcommons - maybe frogs are intergalactic visitors. Apparently amphibians are more reptile like than fish like. Maybe something eel like was a transition species.)

“Tadpoles in small pond,” Photo by Patti Black on Unsplash

And what do we know about amphibian skin - that it is very absorptive. Amphibian skin is more absorptive than our skin which is meant to be protective for drier environments. But our skin is more absorptive than other examples from the kingdom of life.

Embryology is the study of how a baby grows, from one fertilized egg - one ovum that had a sperm deposit genetic material (but no mitochondria) - into a ready to be born fetus, fully developed and ready to be a newborn baby.

The very early embryo is like a hollow ball of cells that folds in on itself, creating layers and a more cylindrical hotdog bun shape which turns into an enclosed long donut shape that has a neural/head end and a tail or spine end. The mesoderm is the middle layer. The endoderm, the inner layer will form the digestive system - it is like our inner donut hole 🍩, or the center of the hotdog bun.

Three weeks after conception, the folding of the blastocyst has occurred and the ectoderm, mesoderm, and endoderm have formed. (mayoclinic.org)

mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/prenatal-care/art-20045302

The skin is part of the integumentary system which develops from the outer ectoderm layer in an embryo. That is happening during the very early lumpy blob phase of fetal development, (not at the tadpole-look-alike stage yet). Our eyes develop from several areas of the blastoderm - the ball of cells stage of fetal development. The lens, eyelid, and corneal epithelium develop from the outer, ectoderm layer. Other parts of the eye are formed from cells from the neural tube, neural crest, and middle folded layer, the mesoderm.

Uveal melanocytes in the eye that produce the pigment melanin are derived from the neural crest which is also the origin of melanocytes in skin and hair. Uveal melanocytes are pigment producing cells within the choroid of the eye, and in the stroma of the iris and ciliary body. Pigment producing epithelial cells in the ciliary, iris, and retina developed from neural ectoderm cells. (Hu, Simon and Sarna, 2008) Melanin helps protect us from oxidative stress and can store toxic metals safely, but that eventually can lead to an excess, and retinal degeneration may occur. (Hu, et al., 2002)

(Hu, Simon and Sarna, 2008)

Our skin can detect light and that signals more melanin production in melanocytes to protect our skin. Melanin acts as an antioxidant during normal function. Age or ill health may lead to it becoming a pro-oxidant.

Aside - in many of the citations I see “no known way to increase melanin production” News to Know —> beta-ionone is a way I know of, to promote melanin production and a better tan. *The fragrance of violets and other spring flowers.

Violet fragrance is the volatile carotenoid called beta-ionone.

The eyes changed position during early evolution - as we were climbing out of the ocean. They moved from a lateral to a dorsal position, better for long distance vision.

Rocky shoreline with a big eyed frog, Photo by Symmol on Unsplash

And this modification occurred sooner than limbs formed during the early development of amphibians.

“We - humans” collectively were probably amphibious before we were mammals.

Lateral eyes would be on the sides of the body and dorsal would be in the back - frog eyes stick up above the head and can see a long way in many directions. Frogs need to quickly escape a hawk that is swooping done from above or catch a fast moving fly with their tongue. They need eyes in the back of their head.

Our eyes would be considered ventral or anterior - in the front of the spine. We need to see what our hands are working on and we can be predators or need to watch for bigger predators.

Disclosure - I do like frogs.

Kruse/Huberman discussion topics:

2022 review article about opsins in the eye, skin and pineal gland. Skin color change in a frog species is the focus - circadian effects vs camouflage effects varied with direction of light. Light from above - circadian changes daily. Light reflected from below, from the surroundings led to camouflage color changes of the frog’s skin. Alpha melanocyte stimulating hormone was involved with darkening the skin during the day - more melanin, and melatonin helped with the lightening the skin at night. (Bertolesi, et al., 2022)

Kruse video topic: Muller cells are support cells in the eye, (Hu, et al., 2002)

Disclaimer This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.

Reference List

(Bertolesi, et al., 2022) Bertolesi GE, Debnath N, Malik HR, Man LLH, McFarlane S. Type II Opsins in the Eye, the Pineal Complex and the Skin of Xenopus laevis: Using Changes in Skin Pigmentation as a Readout of Visual and Circadian Activity. Front Neuroanat. 2022 Jan 21;15:784478. doi: 10.3389/fnana.2021.784478. PMID: 35126061; PMCID: PMC8814574. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814574/

(Chandrasekaran, et al., 2016) Chandrasekaran NC, Sanchez WY, Mohammed YH, et al., Permeation of topically applied Magnesium ions through human skin is facilitated by hair follicles., Magnes Res. 2016 Jun 1;29(2):35-42. https://www.ncbi.nlm.nih.gov/pubmed/27624531

(Gröber, et al., 2017) Gröber U, Werner T, Vormann J, Kisters K. Myth or Reality-Transdermal Magnesium?. Nutrients. 2017;9(8):813. Published 2017 Jul 28. doi:10.3390/nu9080813 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579607/

(Hu, et al., 2002) Hu DN, Savage HE, Roberts JE. Uveal melanocytes, ocular pigment epithelium, and Müller cells in culture: in vitro toxicology. Int J Toxicol. 2002 Nov-Dec;21(6):465-72. doi: 10.1080/10915810290169891. PMID: 12537643. https://pubmed.ncbi.nlm.nih.gov/12537643/

(Hu, Simon and Sarna, 2008) Hu DN, Simon JD, Sarna T. Role of ocular melanin in ophthalmic physiology and pathology. Photochem Photobiol. 2008 May-Jun;84(3):639-44. doi: 10.1111/j.1751-1097.2008.00316.x. Epub 2008 Mar 8. PMID: 18346089. https://pubmed.ncbi.nlm.nih.gov/18346089/

(Martin, et al., 2009) Kevin J. Martin,  Esther A. González and Eduardo Slatopolsky, Clinical Consequences and Management of Hypomagnesemia, JASN, Nov 1, 2009 vol. 20 no. 11 2291-2295, doi: 10.1681/ASN.2007111194 http://jasn.asnjournals.org/content/20/11/2291.long

Pregnancy, Week by Week, Mayo Clinic, https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/prenatal-care/art-20045302

(Waring, Epsom Salt Council) Dr RH Waring, Report on Absorption of Magnesium Sulfate, Epsom Salt Council. [(accessed on 1 October 2015)]; Available online: http://www.epsomsaltcouncil.org/wp-content/uploads/2015/10/report_on_absorption_of_magnesium_sulfate.pdf. *Reference 13 from (Gröber, et al., 2017)

(Walder, et al., 2002) Walder RY, Landau D, Meyer P, Shalev H, Tsolia M, Borochowitz Z, Boettger MB, Beck GE, Englehardt RK, Carmi R, Sheffield VC. Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet. 2002 Jun;31(2):171-4. doi: 10.1038/ng901. Epub 2002 May 28. PMID: 12032570. https://pubmed.ncbi.nlm.nih.gov/12032570/