28. Maestroni, GJ. T-Helper-2 lympocytes as peripheral target of melatonin signalling. J Pineal Res 1995;18:84-9.
29. Reiter RJ, et al. The role of melatonin in the pathophysiology of oxygen radical damage. In: Advances in Pineal Research. Vol. 8.
Comment [c35]: Could not find the other authors
Moller M, Pevet P, editors. London: John Libbey and Co.; 1994. p. 278.
30. Reitar RJ, Robinson J. Melatonin. New York, NY: Bantam Books; 1995. p. 166-7.
31. Shannon M. Alternative medicines toxicology: A review of selected agents. Clin Toxicol 1999;37:709-3.
32. Guardiola-Lemaitre B. Toxicology of melatonin. J Biol Rythms 1997;12:697-706.
33. Barchas J, et al. Acute Pharmacology of Melatonin. Nature 1967;214:919-220.
Comment [c36]: Could not find the other
34. Rubin RL, et al. Neuroendocrine aspects of primary indogenous depression, XI, Xerum melatonin measures in patients and matched
authors.
control subjects. Arch Gen Psychiat 1992;49:558-567.
Comment [c37]: Could not find the other
35. Peres MF, Seabra ML, Zukerman E, Tufik S. Cluster headache and melatonin. Lancet 2000;355:147[letter].
authors.
36. Blau JN, Engel HO. A new cluster headache precipitant: increased body heat. Lancet 1999;354:1001-2.
37. Lissoni P, Barni S, Cazzaniga M, Ardizzoia A, Rovelli F, Brivio F, et al. Efficacy of the concomitant administration of the pineal hormone
melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on IL-2 alone.
Oncology 1994;51(4):344-7.
38. Natural Products Encyclopedia. www.consumerslab.com: Melatonin.
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Accessory Nutrients and Essential Oils
Modified Citrus Pectin
General Features
Modified Citrus Pectin is a dietary supplement that has demonstrated an ability to prevent the spread of cancer
(metastasis), with strong evidence to support its use in the prevention and/or management of prostate cancer
metastasis. Modified Citrus Pectin is a special form of pectin that has been altered in the laboratory by a proprietary
process that shortens the length of pectin’s polysaccharide chain. This results in a lower molecular weight, enabling
the molecule to be absorbed through the intestinal wall into the bloodstream. By contrast, pectin itself cannot be
absorbed from the intestinal tract into the bloodstream and thus, is primarily categorized as a type of water-soluble
fiber with a proven ability to lower cholesterol and provide other health benefits via its actions in the intestinal tract.
Pectin is found in the peel and pulp of citrus fruits such as lemons, grapefruits, oranges and tangerines. Its long chain
of monosaccharides has numerous branches with important binding capabilities, which play a key role in pectin’s
unique anti-metastatic attributes. Therefore, researchers were interested in manipulating pectin’s structure is such a
way as to allow it to be absorbed into the bloodstream, while maintaining its ability to bind to carbohydrate-binding
proteins (glycoproteins) on the surface of metastatic cancer cells, blocking their ability to invade adjacent tissue, and
inhibiting their proliferation and colonization into new tumor masses. As explained below, Modified Citrus Pectin does
not prevent the development of cancer (cancer initiation), but rather appears to play an important role in preventing the
spread of cancer to other tissues (metastasis), which usually is the manner in which cancer death occurs.
Principle Active Constituents
The laboratory modification of citrus pectin to Modified Citrus Pectin yields a galactose-rich pectin product with a lower
molecular weight than citrus pectin in its native (original) form. This structural modification allows Modified Citrus
Pectin to be absorbed from the intestinal tract into the bloodstream, and exert an anti-metastatic effect on cancer cells,
which contain certain carbohydrate-binding proteins (galectins) on their cell surface.
Clinical Application and Mechanism of Action
1. Preventing the Spread of Cancer (Anti-metastatic)
One of the dominant carbohydrates contained within Modified Citrus Pectin is galactose. Galactose has a strong
af inity for binding to the surface of metastatic cancer cells, which express a particular cell surface receptor known
as galectin-3 (a galactoside-binding lectin). In turn, the binding of Modified Citrus Pectin to the galectin-3 receptor
on metastatic cancer cells creates a type of galectin-3 blockade. With the galectin-3 receptor blocked in this
fashion, cancer cells are less able to adhere to other healthy tissues and cells, essentially inhibiting cancer cells
from invading and spreading to new areas and tissues in the body (anti-metastatic ef ect). As well, the blockade of
the galectin-3 receptor prevents cancer cells from adhering to each other, discouraging their ability to form colonies
(tumor mass). If cancer cells are deprived of their own adhesive ability, they fail to thrive and can be more easily
destroyed by the body’s immune system. Thus, Modified Citrus Pectin has been shown to at ach to galectin-3
receptors on metastatic cancer cells, preventing their clustering and colonization into a larger tumor mass and
blocking their ability to spread to other tissues. Interestingly, non-metastatic cancer cells do not have high levels of
galectins on their cell surface. Thus, it appears that these galectins are essential for the spread of cancer
(metastasis) to a very significant degree.
Research into this area, in fact, confirms that galectin-3 receptors play a very pivotal role in the metastasis of
cancer in the body. Galectins on the surface of cancer cells are known for their carbohydrate-binding abilities,
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Accessory Nutrients and Essential Oils
playing an important role in cellular interactions during the metastatic process. In short, galectin-3 receptors bind to
the galactose molecules on neighboring cancer cells, as well as to the other sugars and monosaccharides on the
surface of healthy cells. Upon binding to other cancer cells they encourage the development of a larger tumor
mass (colonization) and upon binding to healthy cells they are able to invade these tissues and propagate further
spread of the cancer. In essence, Modified Citrus Pectin denies metastatic cancer cells of the opportunity of
at aching to other cancer cells and healthy cells, by binding to and fully saturating all of their galectin-3 cell surface
receptors. The importance of this mechanism of action is highlighted by the fact that many human cancer cells
express galectins on their cell surface, including carcinoma of the prostate, breast, colon, and larynx, as well as
lymphoma, melanoma and glioblastoma. Human studies of the colon, stomach and thyroid cancers have also
shown that the amount of galectin produced increases proportionally as the cancer progresses from its early to
advanced stages. Higher galectin levels encourage greater adhesion of cancer cells to each other, and also
facilitates the process of binding to non-cancerous cells at distant sites within the body.1,2,3,4,5,6
There is also evidence to show that Modified Citrus Pectin may augment the immune response in cancer by
enhancing cytotoxicity of CD3+ T-cells and natural killer cells, while also mediating increased monocyte cytotoxicity.
These ef ects have been shown to be due to the presence of rhamnogalacturonan, another constituent of Modified
Citrus Pectin.1
A significant number of animal trials have revealed that Modified Citrus Pectin inhibits metastasis of melanoma
cancer in mice, prostate cancer in rats 1,2,3 with other in vitro studies showing similar ef ects for cancer of the breast
and larynx.1
Human Cancer Studies - A pilot study involving prostate cancer patients who failed first-line androgen-deprivation
therapy, were in relapse after radical prostatectomy, external beam radiation therapy or cryosurgery, and were
Comment [U38]: Spelling? Prostatectomy? Yes
either untreated or of intermittent hormone blockade, demonstrated that supplementation with 15 gms per day of
, prostatectomy is correct
Modified Citrus Pectin (5 gms, three times per day) increased the length of the PSA doubling time by 30% in 4 of 7
patients, one patient had a partial response, one patient had stable disease and one patient did not respond. The
researchers conclude that Modified Citrus Pectin appears to slow the PSA doubling time in prostate cancer patients
with low levels of PSA, and that all patients were still alive three years after the of icial end of the study. This
research abstract of this study was presented at the International Conference on Diet and Prevention of Cancer;
May 28-June 2, 1999, Tampere, Finland.1 As reported by PM Kidd, Ph.D., Modified Citrus Pectin’s apparent safety
and proven anti-metastatic action, and the lack of proven therapies against metastasis would justify its inclusion
into comprehensive orthomolecular anticancer regimes.2,6