(continued from yesterday)
The Migraine
Connection to Sulfite
The air pollutant sulfur dioxide, a sulfiting agent, appears
linked to migraine occurrence.[1]
[2]
Chemically induced sulfite oxidase deficiency is toxic to the brain, primarily
to the cerebral cortex and striatum,[3]
which first area is connected to migraine susceptibility.[4]
Sulfite is a catabolic product of hydrogen sulfide (H2S), an gasotransmitter
found in the brain[5]
that is connected to vasodilation,[6]
and vasodilation has been repeatedly observed in connection with migraines. It
is still unclear exactly how H2S is
broken down in the body; it was recently discovered that there appears to be a previously-unknown
H2S catabolic pathway using neuroglobin.[7]
In most people, sulfite oxidase typically seems able to
handle the amount of sulfite resulting from endogenous hydrogen sulfide
production. However, in the absence of molybdenum, magnesium,[8]
or P5P (active vitamin B6 is involved in making heme, which is part of sulfite
oxidase),[9]
sulfite oxidase might not reach necessary levels of activity, as those three
nutrients are needed to form sulfite oxidase and its component, the molybdenum
cofactor. Moreover, when sulfite oxidase is dealing with a high level of
sulfite, nitrites also are substrates of the enzyme;[10]
the connection between nitrites and migraines has much evidence behind it.[11]
There is also evidence connecting sulfite consumption to migraines.[12]
mARC 1 and mARC 2
Two relatively recently discovered molybdenum-utilizing
enzymes are the mARC 1 and mARC 2 enzymes. They appear to be involved with
nitric oxide (NO) production,[13]
and nitric oxide has long been reported to be involved with headaches,
including migraines.[14]
Molybdenum supplementation might, by facilitating optimal functioning of the
mARC1 and mARC2 enzymes, contribute to appropriate NO production and possibly
less migraine incidence. There is also evidence that interaction of NO and H2S is
connected to migraine pathophysiology,[15]
and NO and H2S cooperatively interact in many ways.[16]
Conclusion
I have written this because I have seen molybdenum help with
migraines in several women with different etiologies (for example, one
connected to hormonal fluctuation, one connected to neck injury and exacerbated
by air pressure changes, and one of unknown causation), and I think current
research supports a hypothesis that molybdenum does so by supporting optimal
activity of the molybdenum-utilizing enzymes sulfite oxidase, mARC 1, and mARC
2. Because chronic migraines could be causing brain damage,[17]
I think it urgent to explore whether molybdenum has potential to alleviate
migraines.
References
[1] Szyszkowicz
M, Rowe BH, Kaplan GG. Ambient sulphur dioxide exposure and emergency
department visits for migraine in Vancouver, Canada. Int J Occup Med Environ Health 2009;22(1):7-12.
[2] Szyszkowicz
M, Porada E. Ambient Sulphur Dioxide and Female ED Visits for Migraine. ISRN Neurology 2012;2012:279051.
[3] Grings
M, Moura AP, Parmeggiani B, Motta MM, Boldrini RM, August PM, Matté C, Wyse AT,
Wajner M, Leipnitz G. Higher susceptibility of cerebral cortex and striatum to
sulfite neurotoxicity in sulfite oxidase-deficient rats. Biochim Biophys Acta 2016;1862(11):2063-2074.
[4] Lang
E, Kaltenhäuser
M, Neundörfer B, Seidler S. Hyperexcitability of the primary somatosensory
cortex in migraine--a magnetoencephalographic study. Brain 2004;127(Pt 11):2459-2469.
[5] Gheibi S,
Aboutaleb N, Khaksari M, Kalalian-Moghaddam H, Vakili A, Asadi Y, Mehrjerdi FZ,
Gheibi A. Hydrogen sulfide protects the brain against ischemic reperfusion
injury in a transient model of focal cerebral ischemia. J Mol Neurosci 2014;54(2):264-70.
[6] Bhatia, M. Hydrogen sulfide as a vasodilator. IUBMB Life 2005;57:603–606.
[7] Bilska-Wilkosz
A, Iciek M, Górny M, Kowalczyk-Pachel D. The Role of Hemoproteins: Hemoglobin,
Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes. Int
J Mol Sci 2017;18(6). pii: E1315. doi: 10.3390/ijms18061315.
[8] Mendel
RR. The Molybdenum Cofactor. J Bio Chem
2013;288:13165-13172.
[9] Heinemann
IU, Jahn M, Jahn D. Arch. The biochemistry of heme biosynthesis. Biochem Biophys 2008;474(2):238-251.
[10] Wang J,
Krizowski S, Fischer-Schrader K, et al. Sulfite Oxidase Catalyzes
Single-Electron Transfer at Molybdenum Domain to Reduce Nitrite to Nitric
Oxide. Antioxidants & Redox Signaling
2015;23(4):283-294.
[11] D'Amico
D, Ferraris A, Leone M, Catania A, Carlin A, Grazzi L, Bussone G. Increased
plasma nitrites in migraine and cluster headache patients in interictal period:
basal hyperactivity of L-arginine-NO pathway? Cephalalgia 2002 Feb;22(1):33-6.
[12] Millichap JG, Yee MM. The diet factor in pediatric and
adolescent migraine. Ped Neurology 2003;28(1):9-15.
[13] Sparacino-Watkins
CE, Tejero J, Sun B, Gauthier MC, Thomas J, Ragireddy V, Merchant BA, Wang J,
Azarov I, Basu P, Gladwin MT. Nitrite reductase and nitric-oxide synthase
activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. J Biol
Chem 2014; 289(15):10345-10358.
[14] Thomsen
LL, Olesen J. A pivotal role of nitric oxide in migraine pain. Ann N Y Acad
Sci 1997;835:363-372.
[15] Wild
V, Messlinger K, Fischer MJ. Hydrogen sulfide determines HNO-induced
stimulation of trigeminal afferents. Neurosci Lett 2015; 602:104-109.
[16] Szabo
C. Hydrogen sulfide, an enhancer of vascular nitric oxide signaling: mechanisms
and implications. Am J Physiol Cell Physiol 2017 Jan 1;312(1):C3-C15.
[17]
Asma Bashir, Richard B. Lipton, Sait Ashina, Messoud Ashina. Migraine and
structural changes in the brain: A systematic review and meta-analysis. Neurology
2013;81(14):1260–1268.
(Disclaimer: I do not prescribe the use of pharmaceutical drugs in any way. I am not a physician, and I reject out of hand any attempt to hold me liable for what boils down to a discussion of food. Any use of a molybdenum supplement should be prudent and guided by the tested tolerable upper intake levels for its usage (see http://lpi.oregonstate.edu/mic/minerals/molybdenum for those limits). Any use of an isolated molybdenum supplement during pregnancy should be under the direction of a medical professional as such supplements have apparently not been tested during pregnancy.)
(Disclaimer: I do not prescribe the use of pharmaceutical drugs in any way. I am not a physician, and I reject out of hand any attempt to hold me liable for what boils down to a discussion of food. Any use of a molybdenum supplement should be prudent and guided by the tested tolerable upper intake levels for its usage (see http://lpi.oregonstate.edu/mic/minerals/molybdenum for those limits). Any use of an isolated molybdenum supplement during pregnancy should be under the direction of a medical professional as such supplements have apparently not been tested during pregnancy.)
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