Limonene Reduces Serotonin During Stress

[murdoc]

Hi!

This is my first post, but I have been following this forum for some months now. I came from Germany so English is not my mother tongue.

I just wanted to share my findings about Limonene and its anti-stress properties. I was interested in essential oils due to their antimicrobial components, but according to Ray and other it seems to be that these oils are often estrogenic. I read somewhere that citrus essential oils are the only essential oils that have antiestrogenic properties.
I could not find much evidence for this, but I stumbled across some studies about Limonene which makes up 90% of orange oil and its effect on brain neurotransmitters.

The first study is free available.

https://www.jstage.jst.go.jp/article/jn ... 4_367/_pdf

Sub-Chronic Effects of s-Limonene on Brain Neurotransmitter Levels and Behavior of Rats

Summary: The present study was designed to gain insight into the effects of s-limonene on the brain after 1-wk administration. For this purpose, neurotransmitters such as dopamine (DA), serotonin (5-HT), μ-aminobutyric acid (GABA), glutamic acid (Glu) and some of their metabolites (DOPAC and 5-HIAA) were determined by HPLC-ECD and amino acid analyzer after 1-wk administration of s-limonene of different concentrations (0, 5, 25, 50 mg/ kg). Significant changes, such as GABA, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT, were confirmed. At the same time, basal hypothalamic-pituitary-adrenal (HPA) activity after 1-wk administration of s-limonene was evaluated by corticosterone. Considering the increment of GABA and the changes of other neurotransmitters, anti-stress effects after 1- wk administration were observed. The experimental results showed that s-limonene could inhibit HPA activity under physical stress and this anti-stress effect of s-limonene may act through the GABAA receptor.

Results

In conclusion, this study has shown that, after 1-wk administration of s-limonene, GABA contents in the brain increased significantly, while the glutamate concentration decreased significantly. These changes did not affect the basal activity of HPA, but when rats were given an acute stress, foot shock, s-limonene showed a strong ability to attenuate the stress responses. The increased corticosterone contents in serum and 5-HT contents in brains declined. This process may be mediated through the GABAA receptor; however, the reason why GABA content was enhanced after s-limonene administration is still unclear. This will be explored in further studies.


Unfortunatly I have no access to this one:

http://www.ncbi.nlm.nih.gov/pubmed/24462212

Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release

Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported to induce sedative effects. In this study, we demonstrated that limonene administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)-induced head twitch response in mice. In rats, pretreatment with limonene decreased hyperlocomotion induced by methamphetamine injection. In addition, limonene reversed the increase in dopamine levels in the nucleus accumbens of rats given methamphetamine. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function.

Any thoughts on this? Orange oil could be a cheap supplement and it gives every food a nice fresh orange flavor.

 

[charlie]

 

[murdoc]

I have looked up some more articles in terms of Limonene.

http://www.altmedrev.com/publications/12/3/259.pdf

It seems to be not toxic.
"In an early study, five healthy males received a single dose of 20 g d-limonene. Although subjects complained about increased bowel movements (2-3 times
daily) and tenesmus, blood tests showed no abnormalities in liver (total protein, bilirubin, cholesterol, AST, ALT, and alkaline phosphatase), kidney (BUN), or pancreatic (amylase) functions."

Furthermore it was used for a variety of clinical studys.
According to them it can disslove gallstones and lead to a relief of heartburn/gastroesophageal reflux disorder symptoms.
"In vitro study suggests it may neutralize the effect of gastric acid by coating the stomach wall and protecting the mucosal lining from gastric acid exposure.Some researchers believe d-limonene may support healthy peristalsis. In a study with guinea pig ileum and rat vas deferens, d-limonene increased the resting tone of these tissues."

It also shows some promising anticancer activities, although it could cause kidney cancer in male rats due to a certain protein. But this is not valid for humans.
"Several experiments demonstrated inhibition of chemically-induced mammary cancer in rodents administered either orange peel oil or pure d-limonene."
It was also used in some clincal trails for breast cancer and colorectal cancer patients and inhibited the growth of tumors to a certrain degree.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585035/#B8
"Its outstanding antimicrobial activities have already been proven against different species of food-related microorganisms, such as Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica, Saccharomyces bayanus"


http://www.lib.okayama-u.ac.jp/www/acta ... _2_111.pdf

Neurite Outgrowth of PC12 Mutant Cells Induced by Orange Oil and d-Limonene via the p38 MAPK Pathway

The presence of d-limonene greatly changes intracellular environments by activating p38 MAPK, resulting in the promotion of the synthesis of a series of proteins. p38 MAPK contributes to the survival of cells. In other words, the kinase plays an important role in stress-dependent differentiation. Furthermore, ERK and p38 MAPK have a greater effect on cell differentiation and protection than does JNK since d-limonene more strongly activates ERK and p38 MAPK than JNK. The results of our study revealed that d-limonene. functions to prevent cell death and circumventing stress.

The illustrations in this study demonstrate the outgrowth of neurite quiet impressive, but to be honest I am not into this kind of research.

Im just curious about this stuff. Maybe it works in very comprehensive way like all the other peat friendly drugs and treatments.
It could lower serotonin, glutamatic acid but also dopamine during stress and act mainly on the GABA-receptor.
It seems to be bowel protective and has some antimicrobial properties. On top of that it could inhibit the growth of tumors.

 

[Parsifal]

I wonder why Ray didn't look further into phyto compounds of plants like essential oils (other than apigenin and naringenin), terpenes, phytotherapy, herbal medicine...
It's really and interesting field but hard to know what is estrogenic or not (a lot of flavonoids seems to be estrogenic, I've even read some studies saying that apigenin and naringenin are estrogenic and it seems that Ray still love them...).

 

[Mmmaurshmallows]

Murdoc,
Thank you for posting this. I too am pretty new here...just started the diet a couple weeks ago. Of course I am already feeling better! Unfortunately my stomach is so broken at this point that adding a little decaf coffee and fresh squeezed oj to my diet caused some bad reflux, which affects my breathing. Very scary!
I've been eating broth for a year or so, but obviously I need extra 'medicine' to heal my gut lining, and I think limonene could do the trick.
Funny thing, I was in Florida over Thanksgiving and our hosts had a kumquat tree on their property. It's like an orange that's been shrunk down to the size of a grape...and you only eat the sweet juicy rind. I love biting into it as you can taste the orange oil as it bursts in your mouth. Something inside me told me I needed to keep eating these delicious little gems. I finally got some more at an upscale store by my house, and have been eating two a day. But they are very seasonal...just during the holiday season. So I ordered some limonene online and now I'll really be able to put it to the test.
I will post in a month or so my (hopefully) good progress and healing for my stomach. I now understand that my lifetime of mental and physical problems have everything to do with my poor broken gut...especially the high serotonin I've always been suffering from.
So thank you again Murdoc for posting this very important research! As a nutritionist I don't know anyone living in toxic chemical and PUFA-filled America today who wouldn't benefit from taking limonene.

 

[murdoc]

Hi,

I have used some organic orange oil in the past to test the influence of limonene. just a few drops definitely increases bowel movements and it works quite well for constipation. i dont have GERD, heartburn or gall bladder issues but it seems to be effective in this area. It is also advertised as a detox supplement because it induces "the liver’s Phase I and Phase II detoxifying enzyme systems and supports normal immune function."

I found out that it binds to adenosine A2A receptors. this explains the calming effect because on the cellular level it has the opposite effect of caffeine. therefore it will also lower dopamine and increase the calcium uptake of cells, which is not good in terms of Peat. But maybe i have taken this out of context.

Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A2A receptors

i am also curious about the solvent properties. Since it dissolve cholesterol, it might be a solvent for orally taken steroids like dhea and pregnenolone. I would rather smell like oranges than DMSO. I dont have access to pure powdered forms of dhea or pregnenolone, so i could not varify this . but it would be interesting... although on the skin it seems to be irritating.

Anyway, i am not sure if this is could be taken without downsides like i have mentioned above.

 

[ddjd]

Hi!

This is my first post, but I have been following this forum for some months now. I came from Germany so English is not my mother tongue.

I just wanted to share my findings about Limonene and its anti-stress properties. I was interested in essential oils due to their antimicrobial components, but according to Ray and other it seems to be that these oils are often estrogenic. I read somewhere that citrus essential oils are the only essential oils that have antiestrogenic properties.
I could not find much evidence for this, but I stumbled across some studies about Limonene which makes up 90% of orange oil and its effect on brain neurotransmitters.

The first study is free available.

https://www.jstage.jst.go.jp/article/jn ... 4_367/_pdf

Sub-Chronic Effects of s-Limonene on Brain Neurotransmitter Levels and Behavior of Rats

Summary: The present study was designed to gain insight into the effects of s-limonene on the brain after 1-wk administration. For this purpose, neurotransmitters such as dopamine (DA), serotonin (5-HT), μ-aminobutyric acid (GABA), glutamic acid (Glu) and some of their metabolites (DOPAC and 5-HIAA) were determined by HPLC-ECD and amino acid analyzer after 1-wk administration of s-limonene of different concentrations (0, 5, 25, 50 mg/ kg). Significant changes, such as GABA, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT, were confirmed. At the same time, basal hypothalamic-pituitary-adrenal (HPA) activity after 1-wk administration of s-limonene was evaluated by corticosterone. Considering the increment of GABA and the changes of other neurotransmitters, anti-stress effects after 1- wk administration were observed. The experimental results showed that s-limonene could inhibit HPA activity under physical stress and this anti-stress effect of s-limonene may act through the GABAA receptor.

Results

In conclusion, this study has shown that, after 1-wk administration of s-limonene, GABA contents in the brain increased significantly, while the glutamate concentration decreased significantly. These changes did not affect the basal activity of HPA, but when rats were given an acute stress, foot shock, s-limonene showed a strong ability to attenuate the stress responses. The increased corticosterone contents in serum and 5-HT contents in brains declined. This process may be mediated through the GABAA receptor; however, the reason why GABA content was enhanced after s-limonene administration is still unclear. This will be explored in further studies.


Unfortunatly I have no access to this one:

Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release. - PubMed - NCBI

Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release

Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported to induce sedative effects. In this study, we demonstrated that limonene administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)-induced head twitch response in mice. In rats, pretreatment with limonene decreased hyperlocomotion induced by methamphetamine injection. In addition, limonene reversed the increase in dopamine levels in the nucleus accumbens of rats given methamphetamine. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function.

Any thoughts on this? Orange oil could be a cheap supplement and it gives every food a nice fresh orange flavor.

Thanks for posting this. So is it actually anti Estrogenic??

And does Limonene contain Naringonen?

 

[LeeLemonoil]

Hard to say if D-Limonene affects estrogen, I'm not aware of any studies.
No, Limonene is a compound/molecule in itself, it does'nt contain anything.
Both Naringenin and Limonene are present in the skin of oranges and lemons though.

 

[ddjd]

Hard to say if D-Limonene affects estrogen, I'm not aware of any studies.
No, Limonene is a compound/molecule in itself, it does'nt contain anything.
Both Naringenin and Limonene are present in the skin of oranges and lemons though.

so a product like this which says its natural orange peel oil probably wont have any naringenin?

Jarrow Formulas, d-Limonene, 1000 mg, 60 Softgels

 

[LeeLemonoil]

so a product like this which says its natural orange peel oil probably wont have any naringenin?

Jarrow Formulas, d-Limonene, 1000 mg, 60 Softgels

Again, no. Limonene is 1 molecule, nothing else.

 

[LeeLemonoil]

Again, no. Limonene is 1 molecule, nothing else.

And Naringenin is not lipophilic, it is therefore not in essential oils.
Probably a little residue though because in contrast to other EOs Citrus oils sometimes are pressed and not distilled. Just eat the peel of organic oranges or Drink orange juice or buy melanon for naringenin

 

[ddjd]

And Naringenin is not lipophilic, it is therefore not in essential oils.
Probably a little residue though because in contrast to other EOs Citrus oils sometimes are pressed and not distilled. Just eat the peel of organic oranges or Drink orange juice or buy melanon for naringenin

ill try eating some peel lol!!

 

[Wagner83]

ill try eating some peel lol!!

You could make marmelade with it, ecstatichamster and Ray mentioned this.

 

[LeeLemonoil]

Good way to eat peel is to sclice the whole fruit and further in mouth-portions then put them in the freezer. Frozen sclices with peel are easier to eat and are a fresh snack. With the benefit that the pulp does'nt squirt all over and you get a little sugar and pulp-nutrients with every slice
Can also Substitute for ice-cubes in Drinks

 

[ddjd]

Hi!

This is my first post, but I have been following this forum for some months now. I came from Germany so English is not my mother tongue.

I just wanted to share my findings about Limonene and its anti-stress properties. I was interested in essential oils due to their antimicrobial components, but according to Ray and other it seems to be that these oils are often estrogenic. I read somewhere that citrus essential oils are the only essential oils that have antiestrogenic properties.
I could not find much evidence for this, but I stumbled across some studies about Limonene which makes up 90% of orange oil and its effect on brain neurotransmitters.

The first study is free available.

https://www.jstage.jst.go.jp/article/jn ... 4_367/_pdf

Sub-Chronic Effects of s-Limonene on Brain Neurotransmitter Levels and Behavior of Rats

Summary: The present study was designed to gain insight into the effects of s-limonene on the brain after 1-wk administration. For this purpose, neurotransmitters such as dopamine (DA), serotonin (5-HT), μ-aminobutyric acid (GABA), glutamic acid (Glu) and some of their metabolites (DOPAC and 5-HIAA) were determined by HPLC-ECD and amino acid analyzer after 1-wk administration of s-limonene of different concentrations (0, 5, 25, 50 mg/ kg). Significant changes, such as GABA, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT, were confirmed. At the same time, basal hypothalamic-pituitary-adrenal (HPA) activity after 1-wk administration of s-limonene was evaluated by corticosterone. Considering the increment of GABA and the changes of other neurotransmitters, anti-stress effects after 1- wk administration were observed. The experimental results showed that s-limonene could inhibit HPA activity under physical stress and this anti-stress effect of s-limonene may act through the GABAA receptor.

Results

In conclusion, this study has shown that, after 1-wk administration of s-limonene, GABA contents in the brain increased significantly, while the glutamate concentration decreased significantly. These changes did not affect the basal activity of HPA, but when rats were given an acute stress, foot shock, s-limonene showed a strong ability to attenuate the stress responses. The increased corticosterone contents in serum and 5-HT contents in brains declined. This process may be mediated through the GABAA receptor; however, the reason why GABA content was enhanced after s-limonene administration is still unclear. This will be explored in further studies.


Unfortunatly I have no access to this one:

Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release. - PubMed - NCBI

Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release

Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported to induce sedative effects. In this study, we demonstrated that limonene administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)-induced head twitch response in mice. In rats, pretreatment with limonene decreased hyperlocomotion induced by methamphetamine injection. In addition, limonene reversed the increase in dopamine levels in the nucleus accumbens of rats given methamphetamine. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function.

Any thoughts on this? Orange oil could be a cheap supplement and it gives every food a nice fresh orange flavor.

did you ever test the serotonin lowering effect?

 

[ddjd]

Again, no. Limonene is 1 molecule, nothing else.

What's the difference between s-limonene and d-limonene?

 

[LeeLemonoil]

They are enantiomers. Scent and taste are different. We are talking about D-Limonene here which can be found in citrus peels mainly but many other plants too, the enantiomer is found in them too but in smaller amounts.

 

[EIRE24]

Is there vitamin C in D limonene? I've found this supplement to be awesome for gut problems

 

[LeeLemonoil]

Perceive think act

 

[Wagner83]

Microcapsule of sweet orange essential oil changes gut microbiota in diet-induced obese rats. - PubMed - NCBI