LONGECITY

Anyone have experience with d-limonene as an anxiolytic or mood enhancer? I have seen studies (abstracts) that would suggest it has the capacity, but cant find any user experiences to reflect that.

I've used it for GERD- cured it for me, BTW, but wasn't paying attention to possible anxiolytic activity. Interesting, though. I may give it a try.

I must have misremembered. Looking at the anxiolytic study again, it appears s-limonene was used. I can find nothing on d-limonene in that regard.

LEF used to include a bit of limonene in with their CoQ10 - presumably to enhance absorption?

Limonene is a solvent, correct?

Would taking a limonene capsule with fat soluble nutrients (D, K2, lycopene, luteine, zeaxantin, tocotrienols) enhance their absorption?
Edited by blood, 29 September 2013 - 07:45 AM.

I must have misremembered. Looking at the anxiolytic study again, it appears s-limonene was used. I can find nothing on d-limonene in that regard.

Byron J Richards is very enthusiastic about D-Limonene (and sells a D-Limonene product).

Snippet from an article from Byron J Richard's Wellness Resources site:

http://www.wellnessr...ty_breast_canc/

Anxiety, Sleep & Mood

D-Limonene is a selective activator of the adenosine A(2A) receptor on cell membranes, which senses molecules outside the cell and in turn triggers activity within the cell. These receptors are vital for nervous system function. The lack of their activation is associated with anxiety, insomnia, and impaired dopamine transmission (addictive tendencies and lack of motivation). A lack of activation of adenosine A(2A) receptors on immune cells results in a hyperimmune response (allergic reactions).

Various doses of d-Limonene have a potent anti-anxiety effect. Even inhaling the vapors of d-Limonene can calm down nervesas well as allergic reactions.

Taking d-Limonene before bedtime will help calm nerves and promote restful sleep, yet another benefit of this multitalented nutrient.

I take a 500 mg capsule of limonene with my evening meal. Around 45 mins after the meal, I do typically feel a sense of relaxation (that feels cleaner somehow than e.g., the sleepiness you get from say eating a bunch of carbs). I'd vaguely wondered what might be causing it. But I take so many supplements with my evening meal - narrowing down what is causing the relaxation response would be a chore.

Some of the studies referenced in Byron J Richard's article - this all seems to be work with mice:

http://www.wellnessr...reduces_anxiety

D-Limonene Reduces Anxiety


Byron's Comments:

D-Limonene has a nerve relaxing effect.

Study Title:

Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action.
Study Abstract:

The aim of the study is to determine the acute toxicity and anxiolytic-like effects of a mixture of cis and trans of (+)-limonene epoxide in animal models of anxiety. After acute treatment with (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg (i.p.) no mortality was noted during 14 days of observation. In general, behavior, food and water consumption showed no significant changes. In open field test, (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg, after intraperitoneal administration, significantly decreased the number of crossings, grooming and rearing (p<0.001). All these effects were reversed by the pre-treatment with flumazenil (25 mg/kg, i.p.), similar to those observed with diazepam used as a positive standard. In the elevated-plus-maze test, (+)-limonene epoxide increased the time of permanence and the number of entrances in the open arms. All these effects were reversed by flumazenil, an antagonist of benzodiazepine receptors. In addition, (+)-limonene epoxide (75 mg/kg) also produced a significant inhibition of the motor coordination (p<0.01), that was reversed by flumazenil. In conclusion, the present work evidenced sedative and anxiolytic-like effects of (+)-limonene epoxide, which might involve an action on benzodiazepine-type receptors. These results indicate that the properties of (+)-limonene epoxide should be more thoroughly examined in order to achieve newer tools for management and/or treatment of central nervous system diseases and anxiolytic-like effects. The LD50 obtained for the acute toxicity studies using intraperitoneal route of administration was 4.0 g/kg. These findings suggest that acute administration of the (+)-limonene epoxide exerts an anxiolytic-like effect on mice, and it could serve as a new approach for the treatment anxiety, since it practically does not produce toxic effects.

Study Information:

de Almeida AA, Costa JP, de Carvalho RB, de Sousa DP, de Freitas RM. Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action. Brain Res. 2012 April 11;1448:56-62.
Department of Chemistry of Federal University of Piauí, CEP 64.049-550, Teresina, Piauí, Brazil.

Anti-Anxiety Properties of D-Limonene


Byron's Comments:

Data showing the nerve relaxing effects of D-Limonene.

Study Title:

Anxiolytic-like activity and GC-MS analysis of ®-(+)-limonene fragrance, a natural compound found in foods and plants.
Study Abstract:

The traditional use of essential oils in aromatherapy has offered numerous health benefits. However, few scientific studies have been conducted with these oils to confirm their therapeutic efficacy. (+)-Limonene is a chemical constituent of various bioactive essential oils. The present study reports on the anxiolytic-like effects of (+)-limonene in an elevated maze model of anxiety in mice. At concentrations of 0.5% and 1.0%, (+)-limonene, administered to mice by inhalation, significantly modified all the parameters evaluated in the elevated plus maze test. The pharmacological effect of inhaled (+)-limonene (1%) was not blocked by flumazenil. Analysis of (+)-limonene using gas chromatography-mass spectrometry (GC-MS) showed its volatility to be high. These data suggest possible connections between the volatility of (+)-limonene and its anxiolytic-like effect on the parameters evaluated in the elevated plus maze test. The data indicate that (+)-limonene could be used in aromatherapy as an antianxiety agent.

Study Information:

Lima NG, De Sousa DP, Pimenta FC, Alves MF, De Souza FS, Macedo RO, Cardoso RB, de Morais LC, Melo Diniz MD, de Almeida RN. Anxiolytic-like activity and GC-MS analysis of ®-(+)-limonene fragrance, a natural compound found in foods and plants. Pharmacol Biochem Behav. 2012 September
Departamento de Ciências Farmacêuticas da Universidade Federal da Paraíba, CEP 58051-970, João Pessoa, Paraíba, Brazil.

D-Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors.


Byron's Comments:

D-Limonene helps an important receptor work better, helping to calm nerves.

Study Title:

Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors.
Study Abstract:

Limonene is a major aromatic compound in essential oils extracted from citrus rind. The application of limonene, especially in aromatherapy, has expanded significantly, but its potential effects on cellular metabolism have been elusive. We found that limonene directly binds to the adenosine A(2A) receptor, which may induce sedative effects. Results from an in vitro radioligand binding assay showed that limonene exhibits selective affinity to A(2A) receptors. In addition, limonene increased cytosolic cAMP concentration and induced activation of protein kinase A and phosphorylation of cAMP-response element-binding protein in Chinese hamster ovary cells transfected with the human adenosine A(2A) receptor gene. Limonene also increased cytosolic calcium concentration, which can be achieved by the activation of adenosine A(2A) receptors. These findings suggest that limonene can act as a ligand and an agonist for adenosine A(2A) receptors.

Study Information:

Park HM, Lee JH, Yaoyao J, Jun HJ, Lee SJ. Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors. Biochem Biophys Res Commun. 2011 January 7;404(1):345-8.
Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, South Korea.

As a bonus, you might get an anti-glycation effect:

Anti-glycation Activity of Limonene


Byron's Comments:

A novel mechanism of health protection.

Study Title:

A novel mechanism for antiglycative action of limonene through stabilization of protein conformation.
Study Abstract:

Inhibition of protein glycation is known to ameliorate secondary complications in diabetes. In the present study antiglycative properties of limonene, a natural product, were evaluated using BSA as a model protein. AMG (aminoguanidine) was used as a positive control. Measurement of total AGEs (Advanced Glycation End-products) and specific AGEs revealed that limonene could inhibit protein glycation to the extent of 56.3% and 75.1% respectively at 50 μM concentration as against 54.4% and 82.2% by AMG at 1 mM. Congo red binding and CD (Circular Dichroism) analysis revealed inhibition of α-helix to β-sheet transition wherein 18.5% β-sheet structures were observed in glycated BSA (bovine serum albumin) as against 4.9% with limonene. Glycation of protein in the presence of urea was enhanced by 18%, while in the presence of limonene it was reduced by 23% revealing the stabilizing effect of limonene. Electrophoretic mobility was similar to the normal control and a zeta potential value of -12.1 mV as against -15.1 mV in diabetic control was observed. Inhibition of glycation in limonene treated samples was confirmed through LC-MS analysis wherein AGEs such as pentosidine, CML (Nε-(carboxymethyl)lysine), CEL (Nε-(carboxyethyl)lysine), MOLD (methylglyoxal-lysine dimer) and imidazolone observed in glycated samples were absent in limonene treated samples. PatchDock studies revealed that limonene could bind to the major glycation sites IB, IIA and IIB sub domains and AMG to the IIIA sub domain. Thus limonene is a potent protein glycation inhibitor that prevents protein glycation through a novel mechanism of stabilization of protein structure through hydrophobic interactions.

Study Information:

Joglekar MM, Panaskar SN, Chougale AD, Kulkarni MJ, Arvindekar AU. A novel mechanism for antiglycative action of limonene through stabilization of protein conformation. Mol Biosyst 2013 July
Department of Biochemistry, Shivaji University, Kolhapur, 416004, Maharashtra, India.

Edited by blood, 29 September 2013 - 07:47 AM.

Might be something to this: I've been taking it again recently, and it does seem to male me less anxious.

A poster on an online forum says that limonene is a 5-HT1A agonist and therefore causes oxytocin release. I can't find a credible source for this, but this kind of makes sense, since oxytocin is known as an anxiolytic.

tintinet, which brand are you taking ?

Here's another study on the effects on 5-HT1A-receptors. No mention of oxytocin though.
http://www.biomedcen...-6882-13-42.pdf

Here's another study on the effects on 5-HT1A-receptors. No mention of oxytocin though.
http://www.biomedcen...-6882-13-42.pdf

Stimulation of 5-HT1A and 5-HT2/5-HT1C receptors induce oxytocin release in the male rat.
http://www.ncbi.nlm..../pubmed/8334526

Better use it for dmt extractions

A poster on an online forum says that limonene is a 5-HT1A agonist and therefore causes oxytocin release. I can't find a credible source for this, but this kind of makes sense, since oxytocin is known as an anxiolytic.

http://www.biomedcen...1472-6882/13/42 maybe?

A poster on an online forum says that limonene is a 5-HT1A agonist and therefore causes oxytocin release. I can't find a credible source for this, but this kind of makes sense, since oxytocin is known as an anxiolytic.

yeah oxycontin would definitely explain the effect

A poster on an online forum says that limonene is a 5-HT1A agonist and therefore causes oxytocin release. I can't find a credible source for this, but this kind of makes sense, since oxytocin is known as an anxiolytic.

yeah oxycontin would definitely explain the effect

Lol?
Edited by mmats, 12 October 2013 - 09:09 PM.

Just might turn out to the the best supplement I've ever taken.

Just might turn out to the the best supplement I've ever taken.

Details? And how much are you taking daily?

I'm taking Swanson 250 mg gels, usually twice a day. I taken many supplements (resveratrol, C60 EVOO, ALT-711, the list is nearly endless), but I've only perceived benefits from very few, e.g., uridine.

Limonene, I think:

1. cured my GERD, some years ago.

2. does seem to help with anxiety.

3. has possible anti-cancer effects: MSK:

"Clinical Summary


Derived from the peels of citrus fruits, D-limonene is used by patients to prevent and treat cancer and has been promoted as a treatment for gastroesophageal reflux. Following oral administration, D-limonene is rapidly metabolized to limonene-1,2-diol, perillic acid, dihydroperillic acid, and uroterpenol ^{(1) (2) (3)}.
In vitro and animal studies suggest that D-limonene has anti-inflammatory ⁽¹³⁾, bactericidal ⁽¹⁹⁾ and anticancer effects ^{(14) (16) (17) (18)}. It was also shown to enhance the activity of docetaxel against prostate cancer cells ⁽¹⁵⁾.
An epidemiological study reported an inverse relationship between citrus peel consumption and squamous cell carcinoma ⁽⁴⁾, but an early clinical trial in breast cancer patients failed to support the observations ⁽⁵⁾⁽⁶⁾.

Further research is necessary to determine if D-limonene has a role in the prevention or treatment of cancer."

I tried d-limonene for GERD and unfortunately it didn't seem to help me at all. I took 500 mg every other day for 16 days; the course is supposed to be 20 days, but since it wasn't helping, I gave up on it.

I didn't notice an anxiolytic effect, and I do have anxiety problems. Since I have plenty on hand, though, I might try it the next time I feel overwhelmed. Otherwise I'll just use it to clean the grease off of the kitchen cupboards.

Can't remember how long I took it before my GERD went away. At the time I was on PPIs and H2 blockers without complete relief. I just took it daily, though- no EOD, IIRC.

Can't remember how long I took it before my GERD went away. At the time I was on PPIs and H2 blockers without complete relief. I just took it daily, though- no EOD, IIRC.

Do you remember how long it took to start feeling better? How much d-limonene did you take? Did you make any dietary modifications/ can you eat what you want now?

When a solvent of fats dissolves those fats, are the fats damaged in any way? Is it safe to take my limonene alongside my fish oil?

http://en.wikipedia.org/wiki/Limonene

Limonene is increasingly being used as a solvent for cleaning purposes, such as the removal of oil from machine parts, as it is produced from a renewable source (citrus oil, as a byproduct of orange juice manufacture). It is used as a paint stripper and is also useful as a fragrant alternative to turpentine.

Can't remember how long I took it before my GERD went away. At the time I was on PPIs and H2 blockers without complete relief. I just took it daily, though- no EOD, IIRC.

Do you remember how long it took to start feeling better? How much d-limonene did you take? Did you make any dietary modifications/ can you eat what you want now?

I think I took 500 mg, maybe up to 4 times a day. I think I usually got some relief fairly quickly. Now I can eat whatever I want and don't get GERD, but I still have irritable bowel issues at times.

I have to say, I'm a little scared of taking that much d-limonene. As blood pointed out, it can be used as paint stripper. I might get desperate enough to try it soon, though. I've got my endoscopy tomorrow; I think all that's for is to rule out anything really awful.

As blood pointed out, it can be used as paint stripper.

I wasn't suggesting that limonene's solvent properties were a bad thing.

I don't have enough knowledge of chemistry to understand what limonene is doing to fats when it dissolves them. Maybe nothing bad.

LEF used to put limonene in one of their CoQ10 products - from an out of date product description text:

Life Extension's new Super Absorbable CoQ10 with d-Limonene is a super-emulsified formulation that significantly increases the amount of CoQ10 absorbed. d-Limonene is a natural compound in orange oil that disperses and breaks down the CoQ10 particles, which reduces their size and makes CoQ10 more absorbable by the body.

Unlike other supplements that contain micronized CoQ10 particles, Super Absorbable CoQ10 with d-Limonene contains smaller, nano-sized CoQ10 particles that enhance this absorption. Research shows that people taking this formula have higher blood levels of CoQ10 than those taking other formulas.

The patent-pending emulsifying system breaks down the fat-soluble CoQ10 particles into millons of microscopic droplets, allowing the body to absorb the CoQ10 much more effectively. Life Extension uses only naturally extracted, cold-pressed orange oil to yield d-Limonene, which has been shown in clinical studies to promote healthy cell division.

Here is the current product:
http://www.lef.org/V...d-Limonene.html

It has about 100 mg of d-limonene per 100 mg of ubiquinone.

I would like to know if limonene taken in conjunction with fat soluble nutrients could enhance the absorption of those nutrients. Does the process of dispersion, emulsification of fat soluble nutrients described by LEF need to take place in e.g., a vat/test tube under controlled conditions, or can it occur in the intestines?
Edited by blood, 14 October 2013 - 07:21 AM.

I'm worried about it stripping the lipids out of my cell membranes. Of course, I drink alcohol occasionally, and that can dissolve lipids, so perhaps not a problem. On the other hand I don't drink turpentine. I'm a worrier, hence the need for an anxiolytic.
Edited by lemonhead, 14 October 2013 - 11:18 AM.

When a solvent of fats dissolves those fats, are the fats damaged in any way? Is it safe to take my limonene alongside my fish oil?

http://en.wikipedia.org/wiki/Limonene

Limonene is increasingly being used as a solvent for cleaning purposes, such as the removal of oil from machine parts, as it is produced from a renewable source (citrus oil, as a byproduct of orange juice manufacture). It is used as a paint stripper and is also useful as a fragrant alternative to turpentine.

Good question.

is this a good product to buy http://www.amazon.co...ords=d-limonene
says pure d-limonene cleansing agent but it mentions YOU CAN SAFELY DRINK IT dunno if it should be consumed very little or it gets bad.

is this a good product to buy http://www.amazon.co...ords=d-limonene
says pure d-limonene cleansing agent but it mentions YOU CAN SAFELY DRINK IT dunno if it should be consumed very little or it gets bad.

Yes, that is a good product to buy. That bottle looks exactly like the bottle I bought from ebay. I used it for cleaning mostly, but I consumed some to kill the body odor of DMSO. That plastic bottle is pretty durable(PET), it will last well over a year before it starts to collapse. Putting it in a glass container from the beginning is a good idea if you aren't going to use it up.quickly.

d-limonene goes through cheaper plastic in a few months, caustic is an accurate description., It is strong stuff. I pour my doses on bread to buffer it. I wasn't looking for an anxiolytic effect so if there was one, I missed it.

When a solvent of fats dissolves those fats, are the fats damaged in any way? Is it safe to take my limonene alongside my fish oil?

Generally speaking, solvents don't harm the thing they dissolve. The sorts of compounds that we usually call "solvents" are not typically very reactive, although there are exceptions. Limonene is an unsaturated hydrocarbon, and fish oil is mostly unsaturated hydrocarbon, with the exception of the glycerol triester part. As long as you don't heat them or expose them to light, I wouldn't expect limonene and fish oil to react. Both of them are susceptible to oxidation; fish oil more so than limonene.

is this a good product to buy http://www.amazon.co...ords=d-limonene
says pure d-limonene cleansing agent but it mentions YOU CAN SAFELY DRINK IT dunno if it should be consumed very little or it gets bad.

Yes, that is a good product to buy. That bottle looks exactly like the bottle I bought from ebay. I used it for cleaning mostly, but I consumed some to kill the body odor of DMSO. That plastic bottle is pretty durable(PET), it will last well over a year before it starts to collapse. Putting it in a glass container from the beginning is a good idea if you aren't going to use it up.quickly.

d-limonene goes through cheaper plastic in a few months, caustic is an accurate description., It is strong stuff. I pour my doses on bread to buffer it. I wasn't looking for an anxiolytic effect so if there was one, I missed it.

why would you consume if you werent looking for the anxyolytic effect ?