D-Limonene: Help for Digestion, Metabolism, Detoxification, Anxiety & Breast Cancer Prevention

Wednesday, February 27, 2013
By: Byron J. Richards,
Board Certified Clinical Nutritionist
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D-Limonene, an oil nutrient called a terpene, is an amazing natural compound found in lemon and orange peels. It has potent antioxidant and anti-inflammatory properties, offers assistance for a variety of metabolic and health problems, has anti-cancer properties, and even helps with weight management.

As a health compound, it has shown a wonderful ability to help with a variety of health issues including improving indigestion, acid reflux, and sluggish bowel. It is a unique fat cleanser and helps clear cholesterol sludge including the sludge in the gall bladder that can form stones. Another aspect of cleansing assistance is that it also helps liver detoxification enzymes. Its calming properties help settle anxiety and therefore can be used as a natural sleep aid. It helps reduce appetite and improve metabolism, making it one more nutrient to assist with healthy weight management. And of great importance, it is a superior nutrient for breast cancer prevention.

All plants synthesize terpenes and they are used by the plant as a natural defense against insects and environmental stress and to repair injuries and wounds. People naturally ingest a wide variety of terpenes in the diet, which is essential for good health. For example, all carotenes are terpenes. Many of the medicinal properties of herbs and plants are based on their terpene activity. Common to terpene activity is the interaction of terpenes with NF-kappaB, the core gene signal that regulates immunity and cellular inflammation in plants and humans.

D-Limonene is a type of terpene called a monoterpene. A person consuming 1 - 2 servings of citrus per day is likely to get 15 - 40 mg of d-Limonene; if the peels are consumed in some way this level may rise to 50 - 90 mg. 

Dietary supplements of d-Limonene are typically produced from the peels of oranges, with a typical dose of 1,000 mg per capsule. This natural compound is safe in high doses and offers assistance for a variety of metabolic and health problems. 

Antioxidant and Anti-inflammatory Properties

Because d-Limonene has potent antioxidant and anti-inflammatory properties, it can be used by any person as part of a general health program. In this case a dose ranging from 1,000 mg to 3,000 mg per day is adequate to significantly support your natural defense systems. Many nutrients contain antioxidant and anti-inflammatory properties, thus d-Limonene is simply another member of your team. The reason to add it to your team is to support specific health issues that it improves, wherein you actually notice the improvement. Let’s review some of these important topics.

Bowel Motility & Digestive Balance of Power

Your bowels must move forward in a timely manner. Preferably you should have a bowel movement shortly after getting up and another after breakfast or lunch. To help move your bowels forward 1,000 mg of d-Limonene per day can be enough, although higher doses may be desired. 

Part of sluggish bowels is often due to an overgrowth of bacteria or Candida albicans that produce toxic metabolites that slow down your colon. Remember, d-Limonene is designed by plants to kill pathogens. It has antibacterial and anti-fungal properties.

Use enough d-Limonene to notice an improvement in the flow of your bowels.

Reflux Indigestion / GERD

Reflux occurs partly because motility is not moving forward at the optimal pace, partly because contents in the stomach are irritating, and often because bile is backing up into the stomach. D-Limonene appears to help all three aspects of this issue. Human studies have found that 1,000 mg per day or even every other day has a beneficial impact on reflux within 10 doses. 

I would like to point out that while acid blocking medication is typically used to suppress symptoms of indigestion, a great deal of reflux is actually caused by bile acids moving backwards into the stomach. This is typically caused by excess food consumption, wherein your liver makes extra bile and stuffs cholesterol in it as a last ditch effort to avoid being overwhelmed by too much food. This readily causes bile stagnation in the gall bladder and bile surges into the digestive tract at the wrong times, which move backwards and cause reflux. 

Because d-Limonene actually dissolves the sludge buildup in the gall bladder it can help solve the problem at its source, along with not eating too often or meals that are too large.

Detoxification & Gallstones

D-Limonene activates several of the Phase I and Phase II liver detox enzymes responsible for clearing toxins. However, I believe its greatest detoxification effect is its ability to clear fat sludge all around the body. The terpenes of d-Limonene literally dissolve fat sludge. For example, turpentine is nonfood terpenes used to dissolve oil based paint. Similarly, terpenes are one of the best compounds for dissolving cholesterol. This is why they have been shown to dissolve cholesterol gallstones. This is more common in women, because estrogen helps to supersaturate the cholesterol into a stagnant condition.

D-Limonene is also active in the lymphatic system where fat-soluble sludge often builds up and causes “plumbing problems.” These include excess mucous, shoulder stiffness, and many types of headaches. Of course, a stagnant lymph system is an immune system handicap.

An overweight person tends to build up stagnant fat in all the wrong places, which needs to be cleansed and metabolized. D-Limonene offers tremendous promise in this regard. At this time no studies evaluate whether or not it can clear out stagnant fat buildup in the arteries or damaged fat accumulation in white adipose tissue (extra pounds of stubborn fat), however, theoretically it would be quite good at these cleansing activities. 

Metabolism & Weight Loss

D-Limonene has a mild appetite suppressant effect, which can be used by anyone to help settle down their appetite.

In a recent animal experiment with diabetic rats, d-Limonene treatment for 45 days was found to significantly improve all major antioxidant enzymes, reducing serious health ramifications from having this metabolic problem. Other animal studies with oils rich in d-Limonene show that it reduces food intake and body weight, and can help lower blood lipids such as cholesterol. In animals fed a high fat diet d-Limonene prevented the buildup in fat that results in a fatty liver while also preventing insulin resistance.

The ability of d-Limonene to act as an antioxidant, suppress food intake, and help fat flow along in metabolism are all attributes that help to solve the type of metabolic problems an overweight person is experiencing.

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 nerves as well as allergic reactions

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

A Novel Nutrient for Breast Cancer Prevention

The intake of d-Limonene deserves serious consideration by any woman concerned about the breast cancer issue. There is almost three decades of animal research, along with some human cancer data. The mechanism of benefit is not limited to breast cancer. The basic nutritional value of d-Limonene and its lack of toxicity, combined with its powerful modes of operation, make it a novel nutritional tool with a great deal of upside potential. It should be considered as part of a healthy diet, exercise, and lifestyle program toward the goal of reducing breast cancer risk.

NF-kappaB is Central to Cell Regulation and Cancer Prevention

The NF-kappaB gene signaling system is essentially a local intelligence within your cells that helps your cells adapt to stress and resolve challenges to survival. When your cells are cruising along in a happy metabolic state, then NF-kappaB has little to do beyond baseline functions. When an attack occurs on a cell, be it a pathogen, a toxin, an injury, stress chemicals, an excess amount of free radicals, or even a shortage of fuel (food) then the NF-kappaB system swings into action to orchestrate the response, similar to a 911 operator helping in a time of need. This system is vital for survival. Many of its initial steps are inflammatory in nature. 

Problems occur when the NF-kappaB system cannot orchestrate a full resolution, often caused by ongoing stress, poor diet, lack of sleep, ongoing infection, ongoing toxin exposure, or other wear and tear factors. You might say the 911 operator is getting frustrated with daily calls from the same person, leaving the system chronically inflamed. Since the NF-kappaB gene signaling system is central to all other types of inflammation of any kind, this is a rather big issue. 

In cancer, cells with a confused and inefficient NF-kappaB system are hijacked—it hijacks the NF-kappaB system itself, which is now used to forward the survival of the cancer cells. 

Many nutrients help calm down NF-kappaB, helping it to do its job more efficiently so that it is less susceptible to being hijacked. For example, the polyphenols in green tea, quercetin, resveratrol, grape seed extract, curcumin, and blueberries all help regulate and calm down NF-kappaB.  Likewise, another broad array of nutrients from the plant kingdom are called terpenes. All carotenes (beta carotene, lyopene, lutein, astaxanthan) are forms of terpenes. The tocotrienol form of vitamin E has a terpene attached to the vitamin E molecule, making it highly biologically active against breast cancer. The NF-kappaB regulating property of terpenes is widely believed as a primary mode of operation for their anticancer properties. In fact, many nutrients can tell the difference between a healthy cell and a cancer cell; they help the healthy cell survive and help to kill the cancer cell, all by “intelligent” interaction with the NF-kappaB signaling system. 

What makes d-Limonene so interesting is that it is highly fat soluble and readily accumulates in fatty tissue such as breast tissue. Once it is in position it helps to fortify healthy NF-kappaB function, a useful tool for promoting breast tissue health. It is unknown what dose of d-Limonene is needed to enable enough breast tissue accumulation of d-Limonene to actually prevent breast cancer. However, researchers at the University of Arizona have proven that even 500 mg of d-Limonene per day readily accumulates in white adipose tissue, indicating that breast tissue accumulation of d-Limonene is likely at doses typical from d-Limonene dietary supplements. If people manage many aspects of their health well, then they have less inappropriate activation of NF-kappaB and would likely need a lower dose to maintain health. If a person is overweight and/or has multiple other risk factors and health issues, then a higher dose of d-Limonene makes sense. 

Animal Tumor Research

Researchers demonstrated in 1984, 1986, 1989, and 1994 that d-Limonene could prevent the formation of experimentally induced breast tumors as well as eradicate existing breast tumors. It did so with very low toxicity, either from the d-Limonene or from the manner in which the cancer was being killed.

In terms of preventing the start of breast cancer, it was found that d-Limonene assisted the liver with detoxification of chemical toxins, preventing the toxins from inducing DNA damage, which led to cancer. In established cancer, d-Limonene utilizes its solvent properties to enter tumors and directly influence cell signaling to help kill the tumor. While it acts as an antioxidant for healthy cells it seems to know the difference when cancer has taken hold. It actually turns up free radical production in cancer cells to help kill them. While this seems to be yet another example of a nutrient displaying intelligent operation within the body, it is more likely that the gene signaling of the human body is quite adept at using common nutrients that have been around since the beginning of human evolution to defend itself.

Other researchers have shown that d-Limonene has anti-cancer properties for gastric cancer, liver cancer, lung cancer, pancreatic cancer, and prostate cancer.

A recent study shows that d-Limonene improves important aspects in the NF-kappaB signaling pathways, thereby preventing and reducing skin cancer. The researchers showed that d-Limonene also restored antioxidant enzyme function for healthy function. 

Human Research

Extensive human research on d-Limonene and cancer is lacking.

In a 2000 study researchers at the University of Arizona found that people living in the sunny Southwest who consumed lemon peels as part of their diet, but not lemons or lemonade, had significantly reduced occurrence of skin cancer.

A few specific patients with advanced breast and colon cancer, taking high dose d-Limonene, were able to hold off progression of the cancer for up to six months. General excitement in the scientific community led to initial human clinical trials using a secondary metabolite of d-Limonene called perillyl alcohol, most likely because this compound could be made into a drug.  Results were disappointing because it is rapidly cleared in the urine, requiring high doses that had too many uncomfortable side effects. D-Limonene does not have these types of problems, but there is a lack of funding for expensive human trials since no drug will result. 

The anti-breast cancer properties of d-Limonene have been extensively reviewed in 1999 by researchers at Purdue University and in 2010 by researchers at the University of Arizona. Read either full-length paper by following the preceding links. These papers explain that d-Limonene exerts its anti-cancer activity by multiple mechanisms including improved immune response, improved antioxidant defense system, improved detoxification, reduction in inflammation, better regulation of the cell cycle, and induction of death signals in cancer cells.

Safety and Absorption of D-Limonene

D-Limonene is rapidly and easily absorbed by the human digestive tract. The oil is spread throughout the body with a preference for fatty tissues such as white adipose tissue, breast tissue, the liver and brain. It exerts direct metabolic activity as well as combines with oxygen to produce a variety of secondary metabolites that are also biologically active. 

An oral dose of 1.6 grams (1,600 mg) in humans was mostly cleared through the urine within 48 hours. A dose of 500 mg from specially prepared lemonade was cleared within 24 hours. The biological activity of a dose of d-Limonene lasts from 12 - 24 hours. A single dose of 20 grams of d-Limonene in healthy men was found to have no toxic effects. Ongoing supplementation with 100 mg per kilogram (about 7 grams per day for an average adult) was found to have no toxic effects. Doses up to 15 grams per day have been used in human breast cancer studies with no toxic effects. High doses of d-Limonene are considered safe for human consumption, with no toxicity to the liver or kidneys. 

At these higher doses a person may experience belching of the oil, which is annoying but is not a health problem. Because the nutrient has relaxing and anti-anxiety properties, higher doses may make a person tired, (which may be quite useful as a sleep aid). Because the nutrient moves peristaltic motion forward, higher doses could cause diarrhea. Because the nutrient unclogs sludge in the gall bladder, higher doses could move stagnant bile rapidly into the digestive tract, which could cause nausea. Because d-Limonene has anti-fungal properties some individuals with an overgrowth of Candida albicans could experience a “die off” from a high dose (nausea or flu-like symptoms). These symptoms have been reported in human studies, in some people, when doses reach 7 - 15 grams per day. In other words, most uncomfortable symptoms with very high dose d-Limonene are not toxic symptoms but reflect a dose that is higher than can be easily metabolized based on a person’s existing metabolic situation. If any of these should occur when taking d-Limonene, cut back the dose or discontinue for a few days, then try a lower dose.

Useful metabolic doses of d-Limonene range from 1,000 mg to 6,000 mg per day (1 – 6 grams per day). 

Summary

The scientific basis to use d-Limonene as an anti-cancer nutrient, especially for breast cancer prevention and treatment, is well established in literature. It is unfortunate that billions of dollars are spent researching toxic cancer drugs when so much benefit could be had by doing the needed human research to prove the most effective dose of d-Limonene for cancer prevention as well as to help treatment in various situations. It is clear that we have a rather sick cancer industry, where putting patents on profitable drugs trumps safe and effective natural health options for people in need. 

Nevertheless, no harm is done by incorporating d-Limonene into your diet, especially if it can be of assistance for other health issues that may also benefit from it. Terpenes are basic components of the human diet, used by our bodies throughout evolution to promote human health.

Originally published 10-12-2012

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