Monoterpenes & Cancer Prevention

limonene

Essential oils, the highly concentrated volatile, aromatic essences of plants, are a mainstay of aromatherapy but are also used in flavoring, perfumes and even as solvents. Researchers now think that two components of orange oil and lavender oil are a good bet to prevent and treat cancer.

Most essential oils contain monoterpenes--compounds that contain 10 carbon molecules often arranged in a ring. Monoterpenes are formed in the mevalonic acid pathway in plants. This is the same pathway that makes cholesterol in animals and humans. Early on, cancer researchers realized that some aspects of cholesterol metabolism were involved in cancer growth. They then discovered that plant monoterpenes interfered with animal cholesterol synthesis, thereby reducing cholesterol levels and reducing tumor formation in animals.1

Limonene and Perillyl Alcohol
Two widely studied monoterpenes are being evaluated for their anticancer activity--limonene from orange peel (Citrus sinensis) and perillyl alcohol from lavender (Lavandula angustifolia), cherries and peppermint.
Because limonene and perillyl affect the pathway that produces cholesterol, they can inhibit cholesterol synthesis, thereby eliminating a minor contributor to cancer formation.2

Monoterpenes also increase the levels of liver enzymes involved in detoxifying carcinogens, an effect that decreases the possibility carcinogens will cause cellular damage.2 In addition, monoterpenes stimulate apoptosis, a cellular self-destruction mechanism triggered when a cell's DNA is badly damaged.3 This safety feature is generally activated before a cell becomes cancerous. Finally, monoterpenes inhibit protein isoprenylation. The cell uses this process to help a protein--in this case the ras protein involved in cell growth--find its proper location within the cell.4 If ras is not in the right place, it becomes overactive and can spur cancerous cell growth.

Laboratory animal studies demonstrate that these two monoterpenes inhibit the formation of chemically induced breast, colon, liver, skin and pancreatic tumors.5 For example, animals fed a diet containing 5 percent orange peel oil had a significantly reduced risk of developing mammary tumors when treated with the chemical tumor inducer DMBA.6 Similarly, animals fed a 5-percent limonene diet had less chance of mammary tumor growth. Researchers noticed that in this experiment rat tumors also regressed, suggesting limonene may treat existing cancer as well as prevent it.

New drugs typically undergo three phases of clinical tests, each more rigorous than the previous: Phase I trials establish a toxic human dose, phase II trials determine a therapeutic dose and how it is metabolized, and phase III trials determine drug effectiveness. Extensive animal studies are done before phase I trials begin.

Phase I trials have so far shown that limonene is well tolerated by cancer patients and has little toxicity.7 Phase II trials, to test how well limonene actually works to reduce cancer, are under way at several institutions including the National Cancer Institute (NCI) in Bethesda, Md.

In other research, perillyl alcohol, a related compound, was found to be five times as active as limonene in regressing tumors.7 A diet of 2.5 percent perillyl alcohol caused 75 percent of chemically induced rat mammary tumors to regress.8 Perillyl alcohol is now being tested in NCI-sponsored phase I clinical trials as a treatment for advanced breast, ovarian and prostatic cancers at the University of Wisconsin, Madison.9 Researchers speculate that perillyl alcohol may also be effective against pancreatic cancer, which is extremely difficult to treat.10

The amount of monoterpenes needed to prevent cancer in humans is not established. Toxicity studies are incomplete, but the high doses required for chemotherapy may cause kidney damage and gastrointestinal problems. Both orange and lavender essential oils are safe to ingest; in fact, orange oil is a common food additive used for flavoring.

Few drugs have been developed that effectively treat cancer, so NCI is constantly searching for potential drug candidates. Many of these candidates, like limonene and perillyl alcohol, are natural products from herbs. For now though, these two concentrated substances remain in the realm of the laboratory--the doses being used in clinical trials are intended for treating cancer and must be monitored by a physician.



References
1. Elson CE, Yu SG. The chemoprevention of cancer by mevalonate-derived constituents of fruits and vegetables. J Nutr 1994;124:607-14.
2. Gould MN. Cancer chemoprevention and therapy by monoterpenes. Environ Health Perspect 1997;105:S977-9.
3. Mills JJ, et al. Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol. Cancer Res 1995; 55:979-83.
4. Hohl RJ. Monoterpenes as regulators of malignant cell proliferation. In: American Institute for Cancer Research. Dietary Phytochemicals in Cancer Prevention and Treatment. New York: Plenum Press;1996.
5. Elson CE. Suppression of mevalonate pathway activities by dietary isoprenoids: protective roles in cancer and cardiovascular disease. J Nutr 1995;125:1666S-72S.
6. [Anonymous]. Clinical Development Plan: l-Perillyl Alcohol, J Cellular Biochem 1996;26S:137-48.
7. Crowell PL, et al. Antitumor effects of limonene and perillyl alcohol against pancreatic and breast cancer. In: American Institute for Cancer Research. Dietary Phytochemicals in Cancer Prevention and Treatment. New York: Plenum Press;1996.
8. Vigushin DM, et al. Phase I and pharmacokinetic study of d-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. Cancer Chemother & Pharmacol 1998;42:111-17.
9. Ziegler J. Raloxifen, retinoids and lavender: "me too" tamoxifen alternatives under study. J Natl Canc Inst 1996;88:1100-1.
10. Stark MJ, et al. Chemotherapy of pancreatic cancer with the monoterpene perillyl alcohol. Cancer Letters 1995; 96:15-21.

Lemon Balm: Do you Know this Herb?

I love herbs that grow prolifically and lemon balm (Melissa officinalis) is one of those. Its in the mint family which explains why it grows so well. Here are some of the other properties I like about lemon balm:

1. Melissa is a great herb to decrease stress and anxiety. It is a mild sedative that promotes sleep. One study found that volunteers who sucked on a lozenge containing lavender oil, extracts from hops, lemon balm and oat showed changes in their EEG that were indicative of relaxation. These changes were similar to those seen in patients taking tranquilizers (1). Another study found that a supplement containing a combination of Melissa officinalis and Valeriana officinalis was able to decrease anxiety in the test participants (2). These results support its uses as a sleep aid, to reduce nervous tension, to reduce infant colic as well as gastrointestinal complaints.

2. Lemon balm has antiviral activity, particularly against the herpes virus (HSV) that causes cold sores. I get cold sores from the stress that I forget to treat with lemon balm. Aqueous (water) extracts of lemon balm inhibit the HSV-1, HSV-2 as well as HSV that is resistant to a popular antiviral drug, acyclovir. This activity is aimed at inhibiting absorption of the virus to cells rather than viral replication which allows it to be effective topically (3,4). Because it is the aqueous extract that works best, it can be used as a simple tea that can be both drank and applied directly to the lips. However, I also find oil based extracts used in a lip balm is also effective. In Germany lemon balm is widely used as a treatment for herpes and cold sores. Studies have found that a cream containing lemon balm can prevent recurrence of cold sores, interrupt the progression of cold sores as well as promote healing (5). Extracts from lemon balm also have antibacterial and antifungal activity (6).

3. Lemon balm is a good source of antioxidants. Water extracts of lemon balm contain phenolic compounds such as hydroxycinnamic acids, rosmarinic acid, chlorogenic acid, ferulic acid and caffeic acids as well as flavonoids (7). Some flavonoids that have been identified in lemon balm include luteolin, luteolin 7-O-beta-D-glucopyranoside, apigenin 7-O-beta-D-glucopyranoside, luteolin 7-O-beta-D-glucuronopyranoside, luteolin 3'-O-beta-D-glucuronopyranoside and luteolin 7-O-beta-D-glucopyranoside-3'-O-beta-D-glucuronopyranoside (8). The internal benefits of antioxidants and flavonoids on the body are well established and so won’t be discussed here, but their benefits to the skin are less well known. Flavonoids have the ability to absorb UV light and so can play a role in protecting the skin against UV damage. One study found that extracts from Melissa were able to decrease the amount of lipid oxidation caused by UV irradiation (9). This is especially important due to the high lipid content of skin and its protective role in preventing moisture loss. I suspect we may be seeing more botanical extracts such as Melissa in our skin care products in the near future.

4. Lemon balm helps improve memory so by consuming it you are better able to remember its previous three benefits. Several studies have found Melissa extracts to improve demented states including Alzheimer’s Disease. In one study, patients with Alzheimer’s Disease who took 60 drops per day of a Melissa extract showed improved cognition after 4 months (10). Dementias such as Alzheimer’s can be associated with agitation, aggression, depression, delusions, wandering, sleep disturbance and hallucinations as well as memory loss. Several of these conditions may be helped with Melissa. A study from the UK, involving severely demented patients, found that rubbing a lotion containing Melissa essential on the hands daily affected several indices tested including decreased agitation and better quality of life (11). Another study, again from the UK found that volunteers taking 1600 mg capsules of dried Melissa leaf had increased memory performance and increased calmness compared to controls (12). The effects of Melissa apparently are due to its ability to increase the activity of acetylcholine, an important neurotransmitter in the nervous system.

These effects on memory combined with its anti-anxiolytic effects also make lemon balm a mood lifter and it can be used for mild depression. The benefits of lemon balm are probably best attained by using it as a tea. I like to blend a little lemon balm with green tea for an afternoon break. Taking some lemon balm at this time of the day better prepares me for the more stressful time of day when my concerns focus on children and preparing a meal. Even though lemon balm tea is best fresh, dried lemon balm is also fine for winter use.

Try these Colorado Aromatics products with Lemon Balm:
Herbal Relief Lip Balm with Lemon Balm
Oasis Spray on Lotion w Lemon Balm
Lemon Balm Face and Body Mist (Hydrosol)


References:
1. Dimpfel W, Pischel I, Lehnfeld R. Effects of lozenge containing lavender oil, extracts from hops, lemon balm and oat on electrical brain activity of volunteers. Eur J Med Res. 2004, 9:423-31.
2. Kennedy, D. O., Little, W., Haskell, C. F., Scholey, A. B., Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress. Phytother. Res. 2006, 20:96-102.
3. Nolkemper S, Reichling J, Stintzing FC, Carle R, Schnitzler P.Antiviral Effect of Aqueous Extracts from Species of the Lamiaceae Family against Herpes simplex Virus Type 1 and Type 2 in vitro. Planta Med. 2006 Nov 7;
4. Dimitrova Z, Dimov B, Manolova N, et al. Antiherpes effect of Melissa officinalis L. extracts. Acta Microbiol Bulg. 1993;29:65–72.
5. Mazzanti G, Battinelli L, Pompeo C, et al. Inhibitory activity of Melissa officinalis L. extract on Herpes simplex virus type 2 replication.Nat Prod Res. 2008;22(16):1433-40.
6. Mimica-Dukic, N., Bozin, B., Sokovic, M., Simin, N., Antimicrobial and antioxidant activities of Melissa officinalis L. (Lamiaceae) essential oil. J Agric Food Chem. 2004, 52(9):2485-9.
7. Dr. Dukes Phytochemical and Ethnobotanical Database, www.ars-grin.gov/duke/
8. Patora J., Klimek, B. Flavonoids from lemon balm (Melissa officinalis L., Lamiaceae). Acta Pol. Pharm. 2002 59:139-143.
9. Trommer, H., Neubert, R.H.H., Screening for new antioxidative compounds for topical administration using skin lipid model systems. J. Pharm. Pharmaceut. Sci. 2005; 8:494-506.
10. Akhondzadeh, S., Noroozian, M., Mohammadi, M., et al., Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomized, placebo controlled trial. J. Neurology Neurosurgery and Psychiatry. 2003; 74:863-866.
11. Ballard CG, O'Brien JT, Reichelt K, Perry EK. Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. J Clin Psychiatry. 2002 Jul;63(7):553-8.
12. Kennedy DO, Wake G, Savelev S, et al. Modulation of Mood and Cognitive Performance Following Acute Administration of Single Doses of Melissa Officinalis (Lemon Balm) with Human CNS Nicotinic and Muscarinic Receptor-Binding Properties. Neuropsychopharmacology 2003; 28:1871-1881.

Microbiology & Cosmetics

Many people do not realize that any cosmetic product that is good for your skin is also a good breeding ground for microorganisms; bacteria and fungus. The reason they are called ‘microorganisms’ is because they are so small that they cannot be seen with the naked eye. They are ‘seen’ by growing them on a petri dish filled with nutrient rich agar to promote their growth. One unseen bacterial or fungal cell will reproduce rapidly in the right conditions to form a colony or clump of cells that is seen by the naked eye on the petri dish. Results of microbiology tests are given as colony forming units which represents each cell that reproduced to form that colony.

Excessive amounts of bacteria and fungus can affect the cosmetic in a number of ways; cause odors, destabilize the emulsion, cause color changes. Microorganisms can also affect the consumer negatively in ways ranging from harmless itching of the skin to serious infection; even blindness if the product is used around the eyes.

The most common microbiology tests for cosmetics are the APC and fungal/yeast test. APC stands for aerobic plate count. This involves diluting the cosmetic product and plating a portion of it on an agar plate with specific nutrients that favor bacterial growth. This test will tell you how many bacteria are in the product at the time of testing. The fungal/yeast test is similar but the sample is plated on an agar plate with nutrients specific to favor fungal growth as well as an antibiotic to prevent bacterial growth. This is used because bacteria can grow faster, overgrowing a plate blocking out the fungi growth making it hard to identify. Plates are placed in an incubator and observed at 48 hours for bacterial growth and 7 days for fungal/yeast colonies. Colonies appear as spots on the plates that are small communities of tens of thousands of individual cells that grew from one cell that came from the cosmetic sample.

Interestingly, the FDA does not require any microbiology testing of cosmetics, but it is the responsible thing to do to protect both consumers and products.

Another important test is the Challenge Test or Preservative Efficacy Test. Although expensive ($500 or more) this test is important for products that are widely sold commercially. It will tell you how well your preservative works in your specific formula. For this test, 5 or more known microbes (both bacteria and fungus) are individually added to the cosmetic sample. Plate counts are done at various time points over 28 days or more. The counts in the product should decrease 90% or more over a 14 day period and not increase again after that.

A less effective version of this test can be called the “common usage test”. For this you would first have your product tested to assure it is without significant contamination initially, then use and abuse a sample for 2-3 weeks (sticking fingers into it) knowing that you are introducing bacteria and fungus into it. Then have it tested again to see how your product holds up to that insult. The counts for the second testing should be as low as the first testing. These tests will give information on how well the preservative you use is working in your system.
All cosmetic products containing water or watery substances (aloe, hydrosols, water based extracts, etc) require a preservative to prevent microorganisms from growing. And all such products should be tested to make sure they are relatively free of these microbes. Products that do not contain preservatives will sooner or later begin to grow microbes just as food products will and could become unsafe for the consumer.

Boulder County Farmers Market Meeting

Today we had the annual meeting for the Boulder County Farmers Market of which I am a member. The Boulder County Farmers market consists of both the Longmont Market and the Boulder Market (two cities in the county). The executive director, Bob D'Alessandro, made some good points about farmers markets that I thought were important enough to share.

He said that farmers markets are important because consumers now have an interest in:
knowing where their food comes from, how it was grown, how far it traveled, how fresh it is, how it was processed and what additives it contains.
Farmers markets are also important because they support local agriculture. This is important to local communities because agriculture provides jobs, brings in sales tax and money to the community. But it also supports our quality of life in a number of ways; farm tours, land conservation, small farms ecologically friendly and importantly farmers markets are fun! They are a great place to socialize, get a bite to eat and see what's new.
Thankfully there are more farmers markets in the country than there are Walmarts!

Boulder County Farmers Market is critical in supporting local agriculture and its mission includes being a place for local farms to sell product and providing support and encouragement for small farmers. The Boulder Market celebrates its 25th year this year and has been named as one of the top 10 markets in the country.
How do you feel about Farmers Markets?