Inducing “cold” by stimulating transient receptor potential cation channel subfamily M member 8 (TRPM8) with menthol led to reduced infection and also resulted in lower levels of mitochondrial fission during infection. Additionally, menthol stabilized levels of mitochondrial antiviral signaling (MAVS) which is known to be tied to mitochondrial dynamics. Taken together, this highlights a novel pathway wherein CVB relies on TRPV1 to initiate proviral mitochondrial fission, which may contribute to the disruption of antiviral immunity.
I suppose there is no harm in trying a peppermint oil capsule supplement. Is there any possibility that it would harm an already inflamed pancreas?
Seems like this information may tie in very well with Prusty's research. Perhaps menthol would normalize the Ron Davis's nanochip.
It was reported that certain viruses induce mitochondrial fission to support infection. We documented that CVB triggers mitochondrial fission and blocking mitochondrial fission limits infection.
Our preliminary findings suggest that CVB relies on TRPV1-mediated mitochondrial fragmentation
Other viruses have also been shown to rely on mitochondrial fission and mitophagy to further infection. Hepatitis B virus induces fission and mitophagy as a method to impair antiviral apoptosis
Cytomegalovirus has been shown to induce mitochondrial fission via the viral antiapoptotic protein vMIA
Menthol treatment reduces mitochondrial fission basally and during CVB infection- HeLa cells were treated with 1 mM menthol and then examined after 6 h.
Can't find or get the full paper. This quote is from the results in google.It is possible that the activation of TRPM8 by menthol coupled sarcoplasmic reticulum Ca 2+ release to mitochondrial Ca 2+ uptake, which promotes the activity of pyruvate dehydrogenase (PDH) and mitochondrial oxidative phosphorylation (OXPHOS), inhibiting reactive oxygen species (ROS) generation.
Lots of stuff in there that sounds it might be relevant to CFS. Have to reread and read more about TRPM8. Also reread about Calcium in ME/CFS. But menthol sounds like it can act as a mitochondrial antioxidant.In vitro, we confirmed that sarcoplasmic reticulum–resident TRPM8 participated in the regulation of cellular and mitochondrial Ca2+ homeostasis in the vascular smooth muscle cells. TRPM8 activation by menthol antagonized angiotensin II induced mitochondrial respiratory dysfunction and excess reactive oxygen species generation by preserving pyruvate dehydrogenase activity, which hindered reactive oxygen species–triggered Ca2+ influx and the activation of RhoA/Rho kinase pathway.
Mitochondria, Ca2+, and reactive oxygen species (ROS) are each integral to vascular function and are thought to be involved in the development of hypertension. Pyruvate dehydrogenase (PDH) and several complexes of electron transport have been reported to be Ca2+ dependent.8 Increased physiological levels of mitochondrial Ca2+ uptake is the coordinated upregulation of the entire oxidative phosphorylation activity.9 PDH is one of the key dehydrogenases of the tricarboxylic acid cycle, the activity of which is blunted by Angiotensin II (Ang II) by increasing PDH phosphorylation in vascular smooth muscle cells (VSMCs).10 Meanwhile, mitochondrial matrix Ca2+ overload impairs mitochondrial function and leads to ROS generation.11 Excessive mitochondrial ROS is implicated in the development of vascular dysfunction.12 Ang II–induced mitochondrial ROS generation promotes Ca2+ influx and, subsequently, contraction in arterial smooth muscle.13 Under pathological conditions of cytosolic Ca2+ overload, mitochondria are capable of taking up large amounts of Ca2+.14 This vicious cycle might be an important factor contributing to the excess mitochondrial ROS production in VSMCs. Indeed, ROS‐mediated upregulation of the RhoA/Rho kinase pathway promotes vasoconstriction and contributes to high blood pressure (BP).15 It is worth investigating whether ameliorating mitochondrial dysfunction disrupts this vicious cycle and attenuates vascular dysfunction in hypertension.
Currently, application of ROS scavengers, which eliminate the total levels of tissue and cellular ROS, has not generally achieved favorable effects on ameliorating cardiovascular diseases.16 Using mitochondria‐targeted antioxidants to alleviate mitochondrial oxidative stress might efficiently attenuate hypertension.
To further examine the effect of TRPM8 activation on mitochondrial ROS mediated RhoA/Rho kinase activation, we performed studies in primary cultured aortic VSMCs. It showed that mitochondrial‐targeting ROS scavenger MitoTEMPO efficiently inhibited Ang II–induced RhoA/Rho kinase pathway activation (Figure 6G through through6J).6J). Menthol treatment similarly inhibited the activation of RhoA pathway in VSMCs from WT but not Trpm8−/− mice (Figure 6G through through6J).6J). These results suggest that the activation of TRPM8 by menthol prevents excessive mitochondrial ROS‐mediated RhoA/Rho kinase pathway activation in the vasculature from CIH.
@Hip Did you ever find anything more? Oral menthol treatment?
I have been taking 300mg menthol x2 daily, which I ground down and capsulated with gloves.
The research and mitochondrial effects sound very promising, but do you think dosing is impossible?
Thanks for the information. I would not want to take more than 600mg at a time. What kind of concentration do you believe that would achieve?
The study I mentioned used peppermint oil capsules containing 187 mg of menthol. So if 187 mg of oral menthol results in a blood concentration of 4.5 μM, then 600 mg oral will achieve about 14 μM.
Which is much lower than the 1000 μM concentration used in vitro, in the mitochondrial study. And this does not even take into account plasma protein binding effects, where ingested substances bind to proteins in the blood, and are effectively lost. Once you take into account protein binding, the effective menthol blood concentration will be even lower than 14 μM.
So unfortunately I don't think there is the remotest chance of obtaining the 1000 μM concentration used in vitro.