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—-Important Message—-
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This natural terpene cures heartburn better than prilosec
If you are taking heartburn stuff, or if you know someone who is (everyone is) read this carefully.
This includes stuff you buy over the counter (and some of it is really bad.)
Pharmacological treatments for heartburn basically fall into three categories: proton pump inhibitors (PPIs), natural terpenes, and antibiotics.
Of the possible treatments, natural terpenes are probably the most rational choice.
PPIs (e.g. omeprazole, prilosec) are strongly associated with osteoporosis, while antibiotics tend towards Candida overgrowth.
And of the natural terpenes, limonene has most consistently been shown to work against heartburn.
Limonene is the major component in the oil of the peels of citrus fruits.
Personal testimonies of this limonene working for heartburn are convincing. The science is too: Limonene does have a plausible mechanism-of-action.
Some of the best proof that limonene works can be found in a U.S. patent, applied for in 2000 and granted in 2002.
The patent author conducted a study using adults with heartburn, 1,000 mg pills of D-limonene, and a rating scale to gauge the effect.
“The inventor, who has had a long history of severe heartburn, has discovered that when he has taken limonene (from 500 mg to 1,000 mg) every other day for 8-20 days, the severity and frequency of his symptoms were alleviated permanently.”
This study was fairly simple, and the results are easy to view as a bar graph.
The percentage of participants rating their heartburn severity as very low, or between 1 and 2, significantly increased in the groups taking D-limonene and NOT in the placebo group.
He got a similar result in his other experiment that included 19 participants.
Symptoms decreased as much in the severe heartburn group as in the mild heartburn group – it just took a few days longer.
And strangely, the group taking D-limonene every other day had a slightly faster resolution of heartburn than those taking it every day.
This seems odd and inexplicable, so it’s probably just the combined effect of randomness and the study’s low statistical power.
Regardless, this does imply that you don’t have to take it every single day. And it hints towards its mechanism.
Nobody is really certain about how D-limonene works… But there are quite a few proposed mechanisms to account for its anti-heartburn activity.
Limonene has been proposed to act as a surfactant, thereby lowering the surface tension of stomach acid and reducing “splashing.”
Yet I find that somewhat unrealistic because hard alcohol does the same but often increases heartburn…
So there must be something else responsible.
Moreover: If limonene acted physically as a surfactant it would have to be taken more often than once every other day to work – perhaps with every single meal.
And there are hundreds of other surfactants that aren’t known to reduce heartburn.
Others suspect that it works to “coat the esophagus” – but, for a low-molecular-weight terpene, it is actually slightly irritating on its own.
Most commercial tablets of D-limonene are simply repackaged orange oil, which is roughly 90% D-limonene… But they do work to reduce heartburn.
There are other reasons to assume that it doesn’t work by “coating the esophagus”’ directly but that it maybe works systemically through its metabolites.
Limonene really appears to work as a painkiller, and here’s why:
In this study, the researchers injected a few groups of rats with high-dose R-(+)-limonene. Then they subjected them to a series of standardized pain tests 30 minutes later.
As others had before, these researchers showed that D-limonene acts as a veritable painkiller when given to rats.
The R-(+)-isomer used here is synonymous with D-limonene, the only isomer found in orange oil.
The opposite isomer of this terpene (S-limonene, (−)-limonene, or l-limonene) also exists naturally, but it’s in mint species, not in citrus fruit.
As a positive control against pain, the researchers used morphine. And they also used its classic antagonist, naloxone.
They found D-limonene to be nearly as effective as morphine in inhibiting pain in the “formalin test” – at the doses used.
(Formalin is a mixture of formaldehyde with other stuff. It can be used as a disinfectant, but it’s also used to cause tissue pain in the lab.)
And when they checked out the effect of naloxone, it predictably abolished the effect of morphine. But it did nothing in regards to D-limonene.
Of course, this doesn’t prove much. But it does indicate that D-limonene works somewhere besides the μ-opioid receptors.
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Limonene was also more effective than indomethacin, a cyclooxygenase inhibitor, at inhibiting acetic acid-induced pain.
This also implies a different mechanism of action than through cyclooxygenase inhibition…
Because hardly anything blocks that enzyme better than indomethacin.
The best hint towards the molecular target of limonene are the types of pain it prevents:
- Limonene was a very effective painkiller against formaldehyde and acetic acid, two pain-inducing molecules.
- But it did nothing to counter the pain during the “hot plate test.”
The membrane receptor TRPV1 is the “heat sensor.” (It is also activated by capsaicin, by the way.)
Since D-limonene failed to reduce heat-induced pain, it’s probably not inhibiting TRPV1 – and not blocking an opioid receptor either.
So it seems this is not a general anesthetic but a specific one.
Formalin-induced pain, on the other hand, is mediated through the similar TRPA1 receptor.
The TRPA1 ion channel mediates acid-induced pain, which is notable insofar as limonene has also been shown to prevent that.
“In conclusion, the study demonstrates the antinociceptive activity of the R-(+)-limonene in the models of chemical nociception induced by acetic acid and formalin.”
Since D-limonene inhibits these two specific types of pain – and not heat-induced pain – it seems like it must be a specific blocker of the TRPA1 ion channel and not the TRPV1 channels.
And this has actually been verified… well, almost.
The full name of TRPA1, when expanded, is transient receptor potential ankyrin one.
A long name like that sounds like something out of Star Wars, which is why it’s almost always abbreviated.
This study showed that TRPA1 pain receptors are central to limonene’s mechanism of action.
But, because they used the L-isomer, the results are not 100% conclusive.
Nonetheless, the two enantiomers of limonene are quite similar and would be identical – if it weren’t for the double bond between the #1 and 2 carbons.
Although you’d expect any two stereoisomers to behave differently in a drug/receptor paradigm, or in any drug/enzyme interaction…
The enantiomers of limonene are more similar to each other than most.
(An enantiomer is a pair of molecules that mirror each other…)
And since they found racemic limonene to have 85% the potency of the L-isomer and not 50% as you’d expect if one were inactive, both the L- and D-isomers should have similar effects on TRPA1.
(A racemic mixture is one that has equal amounts of right-handed and left-handed enantiomeric isomers…)
And like the study with D-limonene, this one showed the same painkilling effect – but with L-limonene.
This natural compound significantly inhibited pain in rats after injections of H2O2 (hydrogen peroxide).
This is another molecule in which its effects are mediated through TRPA1 ion channels.
And they went one step further:
They used genetic engineering to create a group of mice lacking the TRPA1 ion channels and another group lacking the heat-sensitive TRPV1 channels.
The mice lacking TRPA1 were absolutely unresponsive to L-limonene…
This implicates TRPA1 ion channels in executing limonene’s effects.
On the other hand, the mice lacking TRPV1 ion channels showed no difference compared to wild-type mice in their response to limonene.
But now things get somewhat complicated – and a bit weird.
This is because L-limonene actually activates the TRPA1 ion channel in isolated cells and induces pain when injected directly…
Which makes a person wonder how it achieves the opposite effect when given orally!
It must be that a metabolite is responsible…
Not only for that reason but also because it becomes perillic acid when ingested:
In this study, they gave human subjects D-limonene and used high-pressure chromatography (a very sensitive method) to determine its concentration in the plasma afterward.
They also checked for limonene metabolites.
They discovered that essentially all D-limonene is rapidly converted into perillic acid, uroterpinol, and perillyl alcohol soon after ingestion.
This could be how limonene: (1) activates TRPA1 in vitro, (2) induces pain when applied directly, yet (3) has the opposite effect after enough time has elapsed.
In a similar fashion, limonene induces pain in humans yet reduces heartburn when taken for a few days.
“Perillic acid was present in plasma at levels higher than d-limonene and other d-limonene-derived metabolites. Plasma d-limonene concentrations were between 20 and 50% of perillic acid concentrations.”
This may seem a bit speculative, but there’s actually a study showing a metabolite of limonene inhibiting pain:
This study was very similar to the one above using D-limonene – both used similar dose levels and pain tests.
This study also used a formalin test (among others) for pain and compared the results against morphine as a positive control.
They showed perillyl alcohol to be as effective as D-limonene – demonstrating that perillyl alcohol could account for the antinociceptive (inhibits the sensation of pain) effects attributed to D-limonene.
Besides formalin, they also injected capsaicin, a molecule derived from peppers that induces a warmish pain sensation through TRPV1 receptors.
Surprisingly, perillyl alcohol reduced capsaicin-induced pain as well.
This implies that this metabolite, in particular, could be inhibiting both the TRPA1 and TRPV1 receptors.
Yet perillic acid is actually the primary metabolite of D-limonene. And, unfortunately, there are no pain studies published using that.
But when all the evidence is taken together, it really does seem that perillic acid is a potent inhibitor of TRPA1 pain receptors – and perhaps also TRPV1 receptors as well.
The TRPA1 ion channels are expressed in the throat.
Scientists assume that is the reason for the burning sensation after drinking virgin olive oil.
Olive trees produce oleocanthal, a specific activator of TRPA1 ion channels.
Cinnamaldehyde also activates TRPA1 ion channels… If you’ve ever had a shot of cinnamon liqueur it’s clear that these receptors are expressed in the throat.
The only other mechanism, besides this one, that could plausibly account for the time-delayed effects of limonene are bacterial and/or fungal in nature.
But despite H. pylori (bacteria) and C. albicans (fungus) contributing to heartburn in some cases, that would imply antibiotics should be effective…
In that case, colloidal silver, fluconazole, penicillin, and oregano oil should work too.
But of the dozens of terpenes tested for antibacterial activity, limonene is actually one of the weakest.
Thus it really seems that limonene reduces heartburn symptoms (1) not by reducing stomach acidity, (2) not by preventing gastric reflux, and (3) not by killing pathogens…
…but actually through its metabolites accumulating and blocking TRPA1 pain receptors in the throat.
“The percentage of participants achieving complete relief of symptoms gradually increased over time, with 79% of the participants achieving complete relief by day 14”
—-Important Message—-
Use this to amplify your sex drive x10
You only need 3 drops of this natural mineral – but it has to go in the right place…
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And then your libido gets a boost and you’re full of confidence.
And all you have to do is paint it on and watch it grow.
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- Wilkins Jr, Joe. "Method for treating gastrointestinal disorders." U.S. Patent No. 6,420,435. 16 Jul. 2002. https://patents.google.com/patent/US6420435
- Al-Saadi, Narjis Hadi Mansoor. "Determination of some chemical compounds and the effect of oil extract from orange peel on some pathogens." Journal of Kerbala University (2009) https://www.iasj.net/iasj?func=fulltext&aId=46160
- Tomaz-Morais, J. F. "Orofacial antinociceptive activity of (S)-(−)-perillyl alcohol in mice: a randomized, controlled and triple-blind study." International Journal of Oral and Maxillofacial Surgery (2017) https://www.sciencedirect.com/science/article/pii/S0901502717300449
- Kaimoto, T. "Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene." European Journal of Pain (2016) https://onlinelibrary.wiley.com/doi/abs/10.1002/ejp.840
- do Amaral, Jeferson Falcao. "Antinociceptive effect of the monoterpene R-(+)-limonene in mice." Biological and Pharmaceutical Bulletin (2007) https://www.researchgate.net/profile/Brinell_Moura/publication/6234771_Antinociceptive_Effect_of_the_Monoterpene_R--Limonene_in_Mice/links/09e4150cb21cf8e208000000.pdf
- Chow, Sherry. "Pharmacokinetics of perillic acid in humans after a single dose administration of a citrus preparation rich in d-limonene content." Cancer Epidemiology and Prevention Biomarkers (2002) http://cebp.aacrjournals.org/content/cebp/11/11/1472.full.pdf
- Heartburn | Pyrosis | MedlinePlus https://medlineplus.gov/heartburn.html
- Heartburn - Symptoms and causes - Mayo Clinic https://kcms-prod-mcorg.mayo.edu/diseases-conditions/heartburn/symptoms-causes/syc-20373223