I have been retired for two years, however, prior to that my expertise was in the treatment of headaches.
First - CGRP is related to calcitonin primarily in their names. Treating migraine with CGRP-inhibiting drugs, whether pill or monoclonal antibodies does not affect calcitonin levels.
Second - I put pretty much all my patients on magnesium. It was rare that magnesium alone was sufficient to suppress migraines, although it sometimes reduced frequency and severity.
Migraine is a complex disorder, and not everyone responds to simple things like magnesium or propranolol (which has a significant adverse effect profile for many people). I would not personally prescribe a drug with such outrageous costs unless it was literally the last option, and there are many others available. I recall that Merck had a CGRP small molecule pill, and never took it to market because of liver enzyme elevations. The anti-CGRP monoclonal antibodies are huge molecules, and are metabolized differently.
Capsaicin products have been tried; most patients don't tolerate them.
Thank you for your feedback on this. Agreed about complexity and tolerance issues. The crime here is withholding information about potentially more effective, cheaper alternatives that may help.
I can help them with magnesium and vascular disease. Adequate magnesium can help reverse vascular plaques. Cholesterol seems to be more of a waxy spackle used by the body to try to control excess calcium in a way that contains its electrical activity. We need adequate protein to make mineral transport and adequate magnesium to keep calcium out of cells and to help the kidneys excrete excess.
"A self-reported dietary intake report from 2012 by Ozawa et al revealed the link between potassium, calcium, magnesium, and the risk of dementia. A long-term study, a statistically significant link between intake and reduced risk of dementia was found, especially with vascular dementia, but not with Alzheimerās Disease." [...] "The mechanism through which the risk of VaD decreased with higher intakes of these minerals is unclear." https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2012.04061.x
Very welcome and thanks for your links. I updated two posts and wrote one. Magnesium was my initial focus of research when I became unemployed. Workaholics who are unemployed have way too much time on their hands.
Extracellular magnesium, if elevated will cause more CGRP production, which can help heal a bone fracture. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats, https://pubmed.ncbi.nlm.nih.gov/27571347/
I started looking into pain when I still had chronic migraines. When I learned about Substance P, I wondered what the P stood for 'Pain'? No, it was early discovery in the history of peptides and proteins. It was P for peptide or protein. I forget which. I have Blog about it maybe.
I am nowhere near done reading yet, Doorless Carp, but I wrote a _ini opus for you in return with what I did think about some of the links and _issing letter of the alphabet.
Thank you. I need to present this all to my doc, who is about as good as they get.
I have a question for the science folks (I am a cellular-mag deficient 'client'). Hypomagnesemia is the word for low serum mag. What is the word...IS there a word?..for low cellular mag?
I need to make sure my understanding is as thorough as it can be.
Some of these studies make me wonder. "...obesity caused by high fat... diet..." I thought that one had been laid to rest.
I wonder about the aging/OA caused by mag deficiency. I had both hips replaced, due to OA, they tell me, at 45. I, now at 60, have no gray hair, and little in the way of wrinkles. As they were replacing my hips, the doctor noted that I had no sign of osteoporosis, despite very little physical activity (recall the 2 rotten hips), for the previous 1.5 years.
Anyway, I will be getting my rbc mag tested again soon. Always interesting
I would call low cellular magnesium "chronic magnesium deficiency". When magnesium is low in the blood stream than it is an acute situation or an extreme chronic deficiency. the body will keep blood levels within a narrow range. Chronic low magnesium can show up as low calcium or potassium blood levels too because the body keeps them in balance with each other within the blood - unless extremely unhealthy.
There can be genetic or gut issues that make gut absorption poor. I need topical magnesium for my best health. Every 4-5 days ideally. Too much isn't good either - that was the message I took from the Rh arthritis study - U shaped curve of risk/benefit. Goldilocks nutrient. We need the just right for us amount.
I wish they'd be more precise. As I understand it, serum mag levels won't vary much before someone has a heart attack, because mag in serum is, in itself, serving a specific purpose to help regulate electrical signals. My serum mag has always been exactly mid-range, even when RBC showed WAY below range.
I think this imprecision clouds the issue. Or maybe that's the point? T'sall good if 98% of folks show perfect serum levels?
I have been retired for two years, however, prior to that my expertise was in the treatment of headaches.
First - CGRP is related to calcitonin primarily in their names. Treating migraine with CGRP-inhibiting drugs, whether pill or monoclonal antibodies does not affect calcitonin levels.
Second - I put pretty much all my patients on magnesium. It was rare that magnesium alone was sufficient to suppress migraines, although it sometimes reduced frequency and severity.
Migraine is a complex disorder, and not everyone responds to simple things like magnesium or propranolol (which has a significant adverse effect profile for many people). I would not personally prescribe a drug with such outrageous costs unless it was literally the last option, and there are many others available. I recall that Merck had a CGRP small molecule pill, and never took it to market because of liver enzyme elevations. The anti-CGRP monoclonal antibodies are huge molecules, and are metabolized differently.
Capsaicin products have been tried; most patients don't tolerate them.
https://practicalneurology.com/articles/2014-may/migraine-spray-aims-to-reduce-headache-pain-with-capsaicin
I know your preference is for natural treatments, but that is just not practical for the majority of migraineurs.
Thank you for your feedback on this. Agreed about complexity and tolerance issues. The crime here is withholding information about potentially more effective, cheaper alternatives that may help.
I can help them with magnesium and vascular disease. Adequate magnesium can help reverse vascular plaques. Cholesterol seems to be more of a waxy spackle used by the body to try to control excess calcium in a way that contains its electrical activity. We need adequate protein to make mineral transport and adequate magnesium to keep calcium out of cells and to help the kidneys excrete excess.
"A self-reported dietary intake report from 2012 by Ozawa et al revealed the link between potassium, calcium, magnesium, and the risk of dementia. A long-term study, a statistically significant link between intake and reduced risk of dementia was found, especially with vascular dementia, but not with Alzheimerās Disease." [...] "The mechanism through which the risk of VaD decreased with higher intakes of these minerals is unclear." https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2012.04061.x
I updated one of my vascular calcification blogs https://open.substack.com/pub/denutrients/p/calcification-of-soft-tissue-hardening-organs-and-softening-bone?r=os7nw&utm_campaign=post&utm_medium=web
Thank you for these links. So many lives could be saved...if only.
Very welcome and thanks for your links. I updated two posts and wrote one. Magnesium was my initial focus of research when I became unemployed. Workaholics who are unemployed have way too much time on their hands.
CGRP being inhibited by capsaicin means that adequate niacin would help migraine sufferers. The method of action is activation of TRPV1 channels. Acidity activating them can cause an increase in CRPP though - at a glance. https://search.brave.com/search?q=CGRP+niacin+TRPV+channel+pubmed&source=desktop
TRPV1 controls acid- and heat-induced calcitonin gene-related peptide release and sensitization by bradykinin in the isolated mouse trachea
https://pubmed.ncbi.nlm.nih.gov/19473241/
Nicotinic acid is a common regulator of heat-sensing TRPV1-4 ion channels https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894441/
Extracellular magnesium, if elevated will cause more CGRP production, which can help heal a bone fracture. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats, https://pubmed.ncbi.nlm.nih.gov/27571347/
CBD/(2AG) may also be involved in CGRP expression. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670541/
Good calls, thanks. It's really worth it's own Substack. CBD:
Preclinical effects of cannabidiol in an experimental model of migraine
https://pubmed.ncbi.nlm.nih.gov/37310430/
I started looking into pain when I still had chronic migraines. When I learned about Substance P, I wondered what the P stood for 'Pain'? No, it was early discovery in the history of peptides and proteins. It was P for peptide or protein. I forget which. I have Blog about it maybe.
I am doubly wrong. P for Powder
"History note: Substance P was one of the first neuropeptides/ brain proteins discovered and it was initially purified in powder form and so was called Substance P for powder. (Neuropeptide Substance P and the Immune Response, https://www.researchgate.net/publication/303895601_Neuropeptide_Substance_P_and_the_Immune_Response)" >> easier for me to find things on my WordPress site https://transcendingsquare.com/2018/09/25/migraines-trp-channels-and-cinnamon/
P for powder? Makes sense š¤£.
Etiology of naming SMAD shows that biochemists cast their nets widely for inspiration. "Mothers against #". Of course.
Another great write-up. Sometimes CADTH can be quite good...other times they are very wishy washy.
I am nowhere near done reading yet, Doorless Carp, but I wrote a _ini opus for you in return with what I did think about some of the links and _issing letter of the alphabet.
https://open.substack.com/pub/denutrients/p/_agnesium-_atters-part-3-by-doorless?r=os7nw&utm_campaign=post&utm_medium=web&showWelcomeOnShare=true
I love your use of positive imagery, that's a great idea for Part 4 on _agnesium
* Carp with no doors would have a beautiful river.
**To be specific about my use in this post. I had a koi in my first post and that didn't feel doorless enough to me.
Much like interpreting a Led Zeppelin album cover you have uncovered the deeper meaning of being doorless and free ;-)
Cyprinus carpio, part 3 another tour de force in the Mag-num Opus.
Well... I've sent this to my endocrinologist!!
She sees me for acromegaly, however I thought the sections on hypothyroid and peripheral neuropathy alone worth her time and attention!!
Another banner, carp!!
I do get particularly enthused when a simple, natural, adjustment to one's diet or lifestyle can be the salve of so much misery!!
Just be grateful you also donāt have to contend with aibohphobia.
Oh, and I'll be swatting ypu about the head and dhouldrts should I see you in person again, sir squire... palindrome
Iāll be sure to armour up first
š
I'm grateful for a good many things!
Thank you. I need to present this all to my doc, who is about as good as they get.
I have a question for the science folks (I am a cellular-mag deficient 'client'). Hypomagnesemia is the word for low serum mag. What is the word...IS there a word?..for low cellular mag?
I need to make sure my understanding is as thorough as it can be.
Some of these studies make me wonder. "...obesity caused by high fat... diet..." I thought that one had been laid to rest.
I wonder about the aging/OA caused by mag deficiency. I had both hips replaced, due to OA, they tell me, at 45. I, now at 60, have no gray hair, and little in the way of wrinkles. As they were replacing my hips, the doctor noted that I had no sign of osteoporosis, despite very little physical activity (recall the 2 rotten hips), for the previous 1.5 years.
Anyway, I will be getting my rbc mag tested again soon. Always interesting
Am I just weird?
I would call low cellular magnesium "chronic magnesium deficiency". When magnesium is low in the blood stream than it is an acute situation or an extreme chronic deficiency. the body will keep blood levels within a narrow range. Chronic low magnesium can show up as low calcium or potassium blood levels too because the body keeps them in balance with each other within the blood - unless extremely unhealthy.
There can be genetic or gut issues that make gut absorption poor. I need topical magnesium for my best health. Every 4-5 days ideally. Too much isn't good either - that was the message I took from the Rh arthritis study - U shaped curve of risk/benefit. Goldilocks nutrient. We need the just right for us amount.
Hypomagnesemia seems to be used as the catchall term, but routine tests wouldn't be of your tissues or bone.
Keep us updated on your progress!
I wish they'd be more precise. As I understand it, serum mag levels won't vary much before someone has a heart attack, because mag in serum is, in itself, serving a specific purpose to help regulate electrical signals. My serum mag has always been exactly mid-range, even when RBC showed WAY below range.
I think this imprecision clouds the issue. Or maybe that's the point? T'sall good if 98% of folks show perfect serum levels?
73 minute read per Substackš¤ is that still a novelette? Or a novella? š¤š
It's borderline novella length. Hopefully a page-turner ;-)
It was. The funny parts helped and the quest for magnesium on websites gave it an action adventure feel.