Citrus pectin is a complex polysaccharide (long-chain carbohydrate) obtained from the peel and pulp of citrus fruits such as lemons, grapefruits, oranges and tangerines. This long chain of sugars has numerous branches with important binding capabilities that are related to pectin's unique anti-metastatic, cholesterol reducing and detoxifying attributes. Both the molecular weight and the structure of the chain influence the binding properties of the pectin.
Modified citrus pectin refers to citrus pectin which has been hydrolyzed or broken down into shorter molecular chains with smaller molecular weights resulting in a more absorbable substance with an enhanced ability to bind to its target sites. In the laboratory, this is done by heat and pH modification.
Galactose, a natural sugar found on the branches of the pectin molecule, has an affinity for galectin-3 proteins on the cancer cell surface. This naturally occurring sugar is felt to play a role in the ability of MCP to inhibit cancer metastasis.
Modified Citrus Pectin in the Prevention and Treatment of Prostate Cancer
A study published in the Journal of Agriculture and Food Chemistry suggests that a component in citrus pectin may help prevent prostate cancer. The study is the result of collaborative research among scientists at the Texas A&M-Kingsville Citrus Center at Weslaco, the University of Texas-Pan American at Edinburg and Texas A&M's Institute of Biosciences and Technology (IBT) at the Texas Medical Center in Houston.
Pectin is a complex carbohydrate found in many plants, but is most abundant in citrus and has already been shown to reduce cholesterol and blood sugar. While the current study focused mainly on prostate cancer, scientists say pectin may also inhibit other types of cancer. Dr. Bhimu Patil, a physiologist at the Citrus Center who isolated pectin from four citrus varieties, said the study is preliminary but justifies further investigations in pre-clinical animal models, then possibly in humans.
A Texas A&M-Kingsville graduate student, Yan Liu, who worked under Dr. Patil and recently completed her master's degree, conducted a major part of this study, Patil said. "This is the first study that identifies a specific molecular target by which citrus pectin may affect the development of cancer," Patil said. The study shows that a component derived from pectin can effect the mis-communication that occurs between cells of the prostate that can lead to malignancy, the life-threatening stage of cancer. "There's cross-talk among cells of the prostate that keeps the prostate healthy," said Dr. Wallace McKeehan, a cell biologist at IBT. "During malignancy, the signals get garbled and the cells don't understand each other. You end up with rogue cells that are not behaving properly because they are not getting the right signals. They begin signaling and stimulating themselves and grow too much." Overgrowth of cells, or the failure to properly stop growth, is a symptom of cancer, McKeehan said. "We've plugged the elements of citrus pectin into the signal mechanisms that have gone haywire and shown that pectin can potentially effect that system and set it back to normal," he said.
The Phase II clinical trial investigating the effects of MCP in recurrent prostate cancer has been completed and was published in Prostate Cancer and Prostatic Diseases. Since an earlier pilot trial had demonstrated the effectiveness in slowing down the rise of prostate specific anitgen (PSA) in a men with prostate cancer, a longer, more controlled study was undertaken in men where standard treatment (radical prostatectomy, radiation, or cyrosurgery) was initially successful (PSA = 0) but then subsequently PSA began to rise. This type of cancer recurrence typically represents a more aggressive form of cancer. The study results are remarkable.
Seventy percent of the men treated experienced a significant slowing of the rise in their PSA representing a slowing of disease progression. The details are as follows. Ten patients experiencing cancer recurrence were given 15 grams of modified citrus pectin per day for one year. Eight of the patients responded to the treatment. Seven out of ten patients had a statistically significant response and a eighth patient responded with a 78% lengthening of his PSA progression which was not statistically significant, but certainly clinically relevant. Six out of the ten subjects more than doubled their PSA doubling time. This increase in the PSA doubling time means a significant reduction in the chance of a premature death from cancer.
While MCP alone isn't a cure for prostate cancer, it is an important adjunct to standard treatment or a valuable nutrient for men in "watchful waiting". It also has many other health benefits which may contribute to a person's quality of life while they meet health challenges such as cancer.
While the mechanism of action of this important nutrient involves the MCP polysaccharide chain interacting with galectin molecules on the surface of cancer cells and blocking the ability of the tumor to grow and spread, new research supports a broader range of action in maintaining optimal health and preventing cancer. This year a pilot trial demonstrated that MCP increases the urinary excretion of toxic metals and additional research with pectin suggests that MCP may have a systemic effect on the immune system which will help assist immune cells in detecting and destroying cancer.
Two studies published recently in prestigious peer reviewed journals have again demonstrated the role of MCP in the prevention and treatment of cancer. These studies are significant because they represent a complementary therapeutic approach to prostate cancer that is non-toxic, all natural, and synergistic with traditional approaches.
The data from a phase II clinical trial using Modified Citrus Pectin for biochemical recurrence of prostate cancer was just published in the journal "The Prostate". The manuscript validated a new statistical method of evaluating the effectiveness of any nutritional supplement or drug. While the statistical method was satisfactorily peer reviewed, the methods and results of the clinical trial were not scrutinized. However, all the preliminary clinical data was presented and from a clinical perspective the results are very encouraging.
Twelve patients were given 15 grams of Modified Citrus Pectin per day for one year. All patients began the study after their PSA (prostate specific antigen) began to rise (biochemical relapse) following treatment designed to destroy the primary tumor in the prostate. Out of 12 patients with biochemical relapse of prostate cancer, only two patients didn't respond to the treatment. Nine out of twelve patients had a statistically significant response and a tenth patient who responded with a 78% lengthening of his PSA progression had a P value of 0.053 (close to the statistically significant response of P value<0.05). The analysis of the data shows that 75% of subjects had a statistically significant response. Six out of the twelve subjects MORE THAN DOUBLED their PSA doubling time. This translates to cancer progression slowing down by MORE THAN 50%. Increase in PSA doubling time for these patients varied between 129% and 941%. Two additional subjects had a DECREASE in their absolute PSA values.
This is an interesting and an unexpected observation. If MCP was working solely by inhibiting metastasis and tumor emboli formation, as has been hypothesized, you wouldn't expect a decrease in PSA in two out of twelve patients with recurrent disease. A decrease in PSA can only be the result of destruction or inhibition of the active cancer tumor. In addition, the researchers noticed that patients PSA levels began dropping soon after treatment with MCP was initiated. This response to MCP occurred too rapidly to be explained by the previously accepted mechanism of action for MCP. As it turns out, recent research on galectin-3 suggests an important role for this molecule in angiogenesis. If galectin-3 is involved in new blood vessel formation, it would make sense that MCP would also be an anti-angiogenesis agent. And, since galectin-3 molecules are present in a wide range of cancers, the use of MCP would not be limited only to prostate cancer.
Indeed, this is exactly what researchers at Wayne State University have shown in a study published in the Journal of the National Cancer Institute in December 2002. The paper, "Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin," clearly demonstrates that MCP reduces tumor growth, angiogenesis, as well as metastasis in tumors that contain galectin-3 molecules, notably human breast and colon cancer. This supports the hypothesis that MCP is effective against all cancer growths that contain galectin-3, not just those types that have been tested. The majority of cancers, including all breast cancers, express galectin-3 molecules.
In the realm of overly hyped "cancer cures" with little if any scientific validation, MCP is a very important agent for prevention and treatment of cancer. As a result of these two recently published reports on MCP and cancer therapy, we have gained a greater understanding on how Modified Citrus Pectin works as well as its potential benefits.
Title: Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study.
Authors: Guess BW, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI.
Source: Prostate Cancer Prostatic Dis. 2003;6(4):301-4.
Abstract: This trial investigated the tolerability and effect of modified citrus pectin in 13 men with prostate cancer and biochemical prostate-specific antigen (PSA) failure after localized treatment, that is, radical prostatectomy, radiation, or cryosurgery. A total of 13 men were evaluated for tolerability and 10 for efficacy. Changes in the prostate-specific antigen doubling time (PSADT) of the 10 men were the primary end point in the study. We found that the PSADT increased (P-value<0.05) in seven (70%) of 10 men after taking MCP for 12 months compared to before taking MCP. This study suggests that MCP may lengthen the PSADT in men with recurrent prostate cancer.
MCP and the Immune System
Components of MCP activate the immune system. in fact pectin shifts the immune system away from immune responses designed to fight bacterial infections and towards a more balanced immune system, actively searching for cancer or virus infected cells. When the immune system is focused on bacterial infections (a state sometimes called Th2 or antibody dominated immunity) a person tends towards allergies and is more reactive to pollens and food that never used to be a problem. In addition, when the immune system is focused on bacteria, pollen, and odd food particles it "forgets" to do its job looking for cancer cells. When the immune system is on the alert for cancer it is considered in a Th1 or cell mediated immunity state. Maintaining an appropriately balanced immune system is important, especially in chronic diseases and now we have evidence that MCP can make an important contribution to the class of nutrients and herbs that modulate the immune system.
MCP Removes Toxic Metals from the Body
Each day numerous cells in the body become cancerous. It is our immune system that we have to thank for detecting and destroying these cells. Still, for certain individuals, the immune system fails and a clinically relevant cancer occurs. One known suppressor of the immune system is toxic or heavy metals. MCP benefits the immune system by removing toxic metals from the body as demonstrated in a recent pilot trial investigating the metal chelation properties of MCP.
The results from the pilot trial were presented at a recent University of California, Davis Nutritional Toxicology Conference. In the study healthy individuals took 15 grams MCP a day for six days. Twenty-four hour urine samples were collected on day zero (baseline), day one and day six and tested for essential elements and toxic metals. MCP increased the urinary excretion of mercury, lead, arsenic, and cadmium but had no effect on the excretion of essential elements.
The increases in urinary excretion were modest, but the side effects typically experienced by harsher chelators were absent. The therapeutic strength of MCP is its ability to chelate and remove metals directly from the bloodstream, thereby reducing the body burden of metals over time in a slow, gentle manner. This study confirmed this by providing a report of one individual using MCP for 10 months. This person showed a dramatic reduction in the body burden of mercury, lead, arsenic, and nickel indicating ongoing removal of metals by the MCP.
Title: The effect of modified citrus pectin on the urinary excretion of toxic elements.
Authors: Isaac Eliaz, Dorena Rode
Source: Fifth Annual Conference of Environmental Health Scientists: Nutritional Toxicology and Metabolomics, August 2003, University of California, Davis
Background and Objective: Pectin is a soluble fiber effective at binding toxic and radioactive metals and has been applied to environmental clean-up and detoxification in humans. Due to its large molecular size, it is not readily absorbed and its actions are limited to the gut. Modified citrus pectin is a smaller molecular weight compound that can be absorbed into the bloodstream. This study was undertaken to evaluate the effect of modified citrus pectin on the urinary excretion of toxic elements in healthy individuals.
Methods: Seven subjects were recruited from a convenience sample. The subjects ingested 15 grams of Modified Citrus Pectin (MCP) each day for five days and 20 grams on day six. Prior to commencing with the MCP the subjects collected a 24 hour urine sample as baseline. 24 hour urine samples were collected on day one and day six for comparison. The samples were analyzed by ICP-MS (inductively coupled plasma -mass spectrophotometer) for arsenic, lead, mercury, cadmium, aluminum, antimony, beryllium, bismuth, nickle, platinum, thallium, thorium, tin, and uranium.
Results: In the first 24 hours of MCP administration the urinary excretion of arsenic increased significantly (130% of baseline levels, p<0.05). In this same period, the excretion of mercury and cadmium approached significance (150% and 230% of baseline respectively; p<0.1). On day six, urinary excretion was significantly increased for cadmium (150% of baseline, p<0.05). In addition, lead showed a dramatic increase in excretion (560% over baseline) with p<0.08.
Conclusions: Oral administration of modified citrus pectin (molecular weight < 20 kDaltons, degree of esterification <10%) resulted in significant increases in the urinary excretion of arsenic and cadmium. Mercury and lead also demonstrated increased excretion approaching significance. Further investigations into the mechanism by which the urinary excretion of toxic elements was increased is justified; although it is likely the effect is due to the known chelation properties of pectin. This preliminary work suggests that the nutritional supplement, MCP, may assist in the elimination of toxic elements from the body. These results should be verified with a larger scale trial and additional studies involving individuals with toxic element burden is also warranted.
Modified Citrus Pectin Lowers Cholesterol
A joint study by the US Department of Agriculture and KGK Synergize, a Canadian nutraceutical company, identified a class of compounds isolated from the peels of grapefruit and concentrated in citrus pectin that shows promise in animal studies as a potent, natural alternative for lowering LDL cholesterol (so-called 'bad' cholesterol), without the possible side effects, such as liver disease and muscle weakness, of conventional cholesterol-lowering drugs.
The findings, released in the Journal of Agricultural and Food Chemistry, a peer-reviewed publication of the American Chemical Society, the world's largest scientific society, show that the compounds, called polymethoxylated flavones (PMFs), are similar to other plant pigments found in citrus fruits that have been increasingly linked to health benefits, including protection against cancer, heart disease and inflammation.
The study is believed to be the first to show that PMFs can lower cholesterol, the researchers say. "Our study has shown that PMFs have the most potent cholesterol-lowering effect of any other citrus flavonoid," said Dr Elzbieta Kurowska, lead investigator of the study and vice president of research at KGK Synergize in Ontario, Canada. "We believe that PMFs have the potential to rival and even beat the cholesterol-lowering effect of some prescription drugs, without the risk of side effects."
PMFs are found in a variety of citrus fruits. The most common citrus PMFs, tangeretin and nobiletin, are found in the peels of tangerines and oranges. They are also found in smaller amounts in the juices of these fruits. Using hamster models with diet-induced high cholesterol, the researchers showed that feeding them food containing 1 per cent PMFs lowered levels of LDL cholesterol by 32 to 40 per cent. Previous animal studies by others have shown that similar flavonoids, particularly hesperidin from oranges and naringin from grapefruit, also may have the ability to lower cholesterol, although not as effectively as PMFs, according to Kurowska.
Treatment with PMFs did not appear to have any effect on levels of HDL cholesterol, or good cholesterol, the researcher said. No negative side effects were seen in the animals that were fed the compounds, she added. The researchers are currently exploring the compound's mechanism of action on cholesterol metabolism. They now suspect, based on early results in cell and animal studies, that it works by inhibiting the synthesis of cholesterol and triglycerides inside the liver.
A long-term human study of the effect of PMFs on high LDL cholesterol is now in progress. While drinking citrus fruits is full of health benefits, taking PMF supplements could be an easier way to lower cholesterol, since a person would have to drink 20 or more cups a day of orange or tangerine juice to have a therapeutic effect, Kurowska estimates. KGK Synergize already has developed a nutrition supplement containing PMFs combined with a form of vitamin E that seems to enhance the compound's effect, according to Kurowska. Marketed as a cholesterol-lowering agent under the trade name Sytrinol, the supplement recently became available in the US.