Category: Natural chemicals
Introduction and description
Limonene is a colourless liquid hydrocarbon classified as a cyclic terpene.
Terpenes are categorised as monoterpenes, sesquiterpenes and diterpenes. Terpene hydrocarbons tend to be antiviral and antibacterial but depending on their chemistry, they can also be [according to various sources]
“analgesic, antiallergic, anti-inflammatory and hormonal balancing!”
The scientific community are only just starting to investigate these sorts of claims methodically, however, some interesting results are starting to appear.
Limonene takes its name from the lemon, as the rind of the lemon, like other citrus fruits, contains considerable amounts of this compound, which contributes to their odour. But although citrus fruits are one known source, many others exist and we have placed a page in the science section listing all the foods that contain limonene.
Some rather dubious research that involved overdosing rats on limonene, resulted in renal failure in the poor little creatures, however, there is no evidence for carcinogenicity or genotoxicity in humans if you ingest limonene within food products. All chemicals have the potental to be toxic or poisonous at high doses. The IARC classifies D-limonene under 'Class 3: not classifiable as to its carcinogenicity to humans', unless of course you significantly overdose by using an extract and not the plants it is in.
In order to drive this point home, limonene as a pure chemical extracted from the food source and thus at the sort of concentration you might find in an essential oil, is used as a paint stripper and as a solvent in some model airplane glues!
Limonene only has medicinal qualities if it stays within the edible foods it occurs in naturally and, as a consequence, at safe concentrations.
Using the activity described in Dr Duke’s phytochemical database and combining it with information from papers on Pubmed, the uses for limonene are as follows. It needs to be noted that in some cases the research has been on an isolated property and no real explanation for the sequence in which the property is manifested has been determined as yet. As you will see from the list we really are at the beginnings of proper study, but knowing at least some of the findings is a help:
Dr James Duke has established that the limonene within plants is an Ozone-Scavenger. Ozone is a powerful oxidant (far more so than dioxygen) and this high oxidising potential causes ozone to damage mucous and respiratory tissues in animals and plants, above concentrations of about 100 ppb. This makes ozone a potent respiratory hazard and pollutant near ground level.
Ozone precursors are a group of pollutants, predominantly those emitted during the combustion of fossil fuels. Ground-level ozone pollution is created near the Earth's surface by the action of daylight UV rays on these precursors. Methane is also a natural precursor.
There is a great deal of evidence to show that ground level ozone can harm lung function and irritate the respiratory system. Exposure to ozone and the pollutants that produce it is linked to premature death, asthma, bronchitis, heart attack, and other cardiopulmonary problems.
Long-term exposure to ozone has been shown to increase risk of death from respiratory illness. A study of 450,000 people living in United States cities showed a significant correlation between ozone levels and respiratory illness over the 18-year follow-up period. The study revealed that people living in cities with high ozone levels such as Houston or Los Angeles had an over 30% increased risk of dying from lung disease.
Thus any plants that contain limonene and which are planted in profusion near the big polluting cities may have the potential to improve air quality and health
One known activity of limonene is that it is a selective adenosine A2A receptor agonist, which means it is potentially really useful as an aid to relaxation, it will be anti-stress and slightly sedating. This is born out by the research from Dr Duke’s database.
Sedative - Calming; quieting. A substance that quiets nervous excitement;
AChE-Inhibitor - An acetylcholinesterase inhibitor (often abbreviated AChEI) or anti-cholinesterase is a chemical that inhibits the acetylcholinesterase enzyme from breaking down acetylcholine, thereby increasing both the level and duration of action of the neurotransmitter acetylcholine. In cardiac tissue acetylcholine neurotransmission has an inhibitory effect, which lowers heart rate. However, acetylcholine also behaves as an excitatory neurotransmitter at neuromuscular junctions in skeletal muscle [see below]
Myorelaxant – is a muscle relaxant, a chemical that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia
Antispasmodic – any agent that prevents or alleviates muscle spasms (cramps), including agents that quieten spasm
Cancer and tumour activity
Limonene is considered by some researchers to be a significant chemopreventive agent with potential value as a dietary anti-cancer tool in humans. Cancer is caused by toxins, viruses, heavy metals, bacteria, fungi, radiation, and parasites, and since limonene has activity against all these there is every reason to believe that this belief and the research that has gone with it is true. This is further born out by the research from Dr Duke’s database:
Antimutagenic - capable of reducing the frequency of mutation
Antilymphomic – against lymphoma ie any neoplasm of lymphoid or reticuloendothelial tissues; in general use, synonymous with malignant lymphoma; present as apparently solid tumors composed of cells that appear primitive or resemble lymphocytes, plasma cells, or histiocytes. Lymphomas appear most frequently in the lymph nodes, spleen, or other normal sites of lymphoreticular cells; may invade other organs or manifest as leukemia
Apoptotic – stimulating or supporting the natural process of apoptosis. Apoptosis is programmed cell death; deletion of individual cells by fragmentation into membrane-bound particles, which are phagocytized by other cells;
Limonene displays mostly anti-parasitic action external to the body
Acaricide; -are pesticides that kill members of the arachnid subclass Acari, which includes ticks and mites
Nematicide - A nematicide is a type of chemical pesticide used to kill plant-parasitic nematodes
Insectifuge - A substance that drives off [harmful] insects
Insecticide - An agent that kills insects
Candidistat - Candida is a genus of yeasts and is the most common cause of fungal infections worldwide.
Fungistatic - Having an inhibiting action on the growth of fungi
Fungistat; - ditto
Kidney and gall bladder diseases
Antilithic - Preventing the formation of calculi or promoting their dissolution
Histaminic – inducing the immune system to produce histamine. Whether this is helpful or not depends on the context in which it occurs. In wound healing, for example, it would be considered helpful
Immunomodulator - a chemical agent that modifies the immune response or the functioning of the immune system (as by the stimulation of antibody formation or the inhibition of white blood cell activity)
Interleukin-6-Inhibitor - A cytokine derived from macrophages and endothelial cells that increases synthesis and secretion of immunoglobulins by B lymphocytes; also induces acute-phase proteins. In hepatocytes, it induces acute-phase reactants
Antimetastatic - Prevention or inhibition of the shifting of a disease or its local manifestations, from one part of the body to another, as in mumps when the symptoms referable to the parotid gland subside and the testis becomes affected.
Or the prevention or inhibition of the spread of a disease process from one part of the body to another, as in the appearance of neoplasms in parts of the body remote from the site of the primary tumor; results from dissemination of tumor cells by the lymphatics or blood vessels or by direct extension through serous cavities or subarachnoid or other spaces.
Or the prevention or inhibition of transportation of bacteria from one part of the body to another, through the bloodstream or through lymph channels
Bronchoprotectant – this is not in any medical dictionary
Expectorant - Promoting secretion from the mucous membrane of the air passages or facilitating its expulsion. Also an agent that increases bronchial secretion and facilitates its expulsion. Used to expel pathogens from the lung
The overall activity appears to be that it aids digestion
Peristaltic – relating to peristalsis, normally the wavelike muscular contractions of the digestive tract where food is forced onward toward the rectum
Enterocontractant - Entero-: Prefix referring to the intestine; contractant: one that contracts, similar meaning to that above but intestine specific
Lipolytic – supporting and aiding the breakdown of lipids and the hydrolysis of triglycerides into glycerol and free fatty acids
Antiinflammatory - Reducing inflammation by acting on body responses, without directly antagonizing the causative agent;
Antiesophagitic –soothing of inflamed esophagus - esophagitis. Gastroesophageal reflux disease, or GERD, is the most common cause of esophagitis. When you have GERD, stomach acid and juices flow backward into your esophagus.
One fascinating use that is being investigated for limonene is in a diagnostic role. The motive for this investigation is that burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics.
Researchers analysed the breath samples of 30 healthy controls and 31 patients with cirrhosis. The results were then compared. 12 of these patients had their breath analysed again after liver transplant. Although, seven volatiles were elevated in the breath of patients versus controls only five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene had the best diagnostic capability.
The conclusion was that Limonene, methanol and 2-pentanone are breath markers for a cirrhotic liver and thus as markers for early-stage liver disease. Furthermore by monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed.
Limonene is thought to accumulate in the body during liver failure because this organ is the first step in the break-down of limonene. The low water solubility of limonene allows the compound to accumulate in the body fat.
Photosensitizer - A light-absorbing substance that initiates a photochemical or photophysical reaction in another substance (molecule), and is not consumed in the reaction
Transdermal – capable of entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form
Irritant – if applied at high concentrations
Allelochemic – capable of being used by a plant in order to defend itself against herbivores or competing plants.
Antifeedant - a naturally occurring substance in certain plants which adversely affects insects or other animals which eat them
Fungiphilic – this might mean a lover of fungi or loved by fungi thus a symbiotic plant; this contradicts the entry for anti-fungal activity. But it depends on the fungi, both could be true [Ref J. Agric. Food Chem. 43: 2283]
- Cancer prevention by natural compounds 017699
- D-limonene rich volatile oil from blood oranges inhibits angiogenesis, metastasis and cell death in human colon cancer cells 016780
- D-Limonene: safety and clinical applications 020764
- Dr Duke's List of Chemicals and their Biological Activities in: Acinos suaveolens (SIBT. & SMITH) G. DON F. (Lamiaceae) 027648
- Dr Duke's list of Chemicals with Candidistat activity 021074
- Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and β-pinene 016782
- Healing actions of essential oils from Citrus aurantium and d-limonene in the gastric mucosa: the roles of VEGF, PCNA, and COX-2 in cell proliferation 016784
- Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer 016779
- Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors 016776
- Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors 017701
- Limonene, citrus fruits and rheumatoid arthritis 005660
- Limonene: safety and clinical applications. 016777
- Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties 016781
- Patent literature on mosquito repellent inventions which contain plant essential oils--a review 016774
- Plasma metabolomic profiles of breast cancer patients after short-term limonene intervention 016783
- Prevention and therapy of cancer by dietary monoterpenes 017700