Are New Blood Vessels A Good Thing?

blood-vesselsAngiogenesis is the creation of new blood vessels, a process that occurs in both health and disease. When new tissue is formed, as in the healing of a wound or the creation of the placenta, blood vessel formation must occur as well. The body is awash in factors that act to signal the growth and differentiation of various cells, including those of the arteries and veins, and the arterioles, venules, and capillaries. The control of angiogenesis operates through a series of “on” and “off” switches that either stimulate or inhibit the formation of new vessels. If there are too many “ons” and insufficient “offs,” the upset of balance favors the growth of new blood vessels. The opposite also holds true. If a person is healthy, the balance is easily maintained, but in some disease states things get out of hand, in either direction—too many or too few new vessels. You see, tumors also need a blood supply. The nutrients and growth factors supplied by the new blood vessels allow tumors to grow. Because of this, the search for ways to destroy cancer cells is partly focused on anti-angiogenesis. But having too many blood vessels is not limited to tumors. Diseases of the eye (macular degeneration, for example) and chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and periodontal disease are also characterized by proliferation of vascular tissue. (Polverini. 1995) And researchers at the University of British Columbia believe that Alzheimer’s disease may be related to hypervascularization. (Biron. 2011)

Substances that prevent the formation of new blood vessels have been around for awhile. Thalidomide is one of them. This drug caused quite a stir in the 1950’s and 60‘s, after it was found to cause skeletal birth defects. Prescribed as a sedative to prevent morning sickness, thalidomide caused thousands of congenital disorders before it was reined in. Because it has benefits for leprosy patients and some inflammatory and autoimmune disorders, it’s still available. Additionally, its antiangiogenic character makes it an appropriate choice for the treatment of multiple myeloma, a primary tumor of bone marrow. (Singhal. 1999) (Bamias. 2003) If thalidomide is able to interrupt the formation of new blood vessels, you can easily see how the development of a neonate can be disrupted.

To study the effects of antiangiogenic substances, some scientists have chosen fat as the experimental system because of its remodeling capacity. Here they have learned that the manufacture of new blood vessels is important to the viability of adipose tissue, and that if the neovascularization were halted, so would be the proliferation of fat cells. (Rupnick. 2002) This transfer of concept to tumor cells is encouraging. A signaling protein termed VEGF (vascular endothelial growth factor) stimulates the growth of new blood vessels, and it helps to restore the oxygen supply to tissues when blood circulation is inadequate. Its importance in embryonic development is obvious, but its overexpression can be problematic. Solid tumors need VEGF to grow beyond their normally limited size, so they make their own. On the other hand, the body makes angiogenic inhibitors, such as thrombospondin and angiostatin to keep tumors dormant. ( Huang. 2004) Besides thalidomide, there are numerous pharmaceuticals available to interrupt angiogenesis, including bevacizumab (Avastin®) and other monoclonal antibodies, the side effects of which offer a laundry list of ills, including cancer. (Hansel. 2010) How ironic! The majority of these drugs block the activity of VEGF, but there may be other angiogenic factors about which less is known.

Working on the antiangiogenesis strategy proposed by renowned cancer researcher, Judah Folkman, Dr. William Li, of the Angiogenesis Foundation in New York, looked beyond drugs and their costs and toxicity, and identified powerful antiangiogenic molecules in dietary sources. This suggests that dietary enlightenment could offer a safe, readily available, novel strategy for preventing cancer. (Folkman. 2006) (Li. 2012)

Dr. Li discovered that nature has loaded a number of foods, beverages and herbs with naturally occurring inhibitors of angiogenesis: berries, citrus fruits, cruciferous vegetables, mushrooms, tomatoes, red wine, green tea, parsley, garlic, turmeric and dark chocolate, among others. The laboratory names extracted from these foods include brassanin, curcumin, genistein, N-acetylcysteine, resveratrol, silymarin, and selenium. The last-named is the only antioxidant mineral. ( Li. 2012)

A study in India, at the Himalayan Institute of Medical Sciences, found aberrant angiogenesis to be factored in Alzheimer’s disease and AIDS, comparing the modulation of angiogenesis in this century to the antibiotics of the twentieth century. (Bisht. 2010) Sagar, Yance and Wong, working at the McMaster University Department of Medicine, in Ontario, added a litany of herbs to Dr. Li’s initial list, citing their antiangiogenic behavior as being engaged through several interdependent processes that include effects on gene expression and enzyme activities. Besides inhibiting the formation of new vascular tissue, these may directly hinder tumor progression and reduce metastasis by way of other actions, including the interruption of epidermal growth factor reception, the blocking of the cyclooxygenase-2 enzyme, and the obstruction of nuclear factor kappa-B transcription. The herbals, artemisia annua (Chinese wormwood), viscum album (European mistletoe), curcuma longa (curcumin), resveratrol, quercitin, ginger, Panax ginseng, and proanthocyanidin (grape seed extract) are among them. (Sagar, Yance and Wang. 2006)

Not only has a soy-based diet, but also the isolated soy isoflavone, genistein, exhibited anti-cancer properties, particularly in lines of melanoma and mammary carcinoma. As is the case with most non-drug treatments, effect is dose-dependent. Its behavior suggests interference with tumor cell migration. (Farina. 2006) The medicinal mushroom, Agaricus blazei Murrill, common to the tropical rain forests near Sao Paulo, Brazil, has traditionally been used to stimulate the immune system, to treat digestive and circulatory disorders, and to lower cholesterol. But its lipid fraction, ergosterol, which is converted to vitamin D2 when exposed to UV radiation, was found to reduce tumor growth significantly in sarcoma-bearing mice at doses of 400+ mg/kg without side effects, suggesting that either ergosterol or its metabolites inhibits tumor-induced neovascularization. (Takaku. 2001) This is the first report of ergosterol’s antiangiogenic character. Later study of this mushroom found additional antiangiogenic constituents. (Kimura. 2004)

Another popular medicinal mushroom is Ganoderma lucidum, used largely in East Asia. Its attributes include the induction of programmed cell death in tumors (apoptosis), accompanied by the inhibition of cell proliferation and suppression of cell migration, especially in prostate cancer, where VEGF was down-regulated. (Stanley. 2005) It is desirable to keep cancer growth stagnant for as long a time as possible. Black raspberry extract was able to do that, as identified in research at Louisiana State University, where investigators saw potent inhibition of angiogenesis and concomitant vessel growth. Gallic acid was pinpointed as a major agent, which worked best in conjugation with less potent fractions, the synergy of which has yet to be elucidated. (Zhijun. 2005)

By disrupting the growth of new vessels from pre-existing capillaries, the green tea catechin, epigallocatechin gallate (EGCG) interrupts cell tube formation in the angiogenesis process by stopping VEGF signals from reaching their receptors. (Rodriguez. 2006) Likewise, blueberries are antiangiogenic. But these little beauties also have the distinction of being able to regenerate rhodopsin, the ocular molecule responsible for turning light energy onto nerve signals. Chinese researchers also found that blueberries can help to forestall a few age-related chronic diseases, such as diabetes, hyperlipidemia, hypertension, neurodegeneration, and even obesity through its apoptosis, antioxidant and anti-inflammation effects. (Chen. 2010)

If there is a favorite among anti-cancer alternative treatments, curcumin might hog the spotlight. Chemoprevention—the use of chemicals to prevent the development of cancer—is a promising anti-cancer approach with limited side effects compared to traditional chemotherapy. Curcumin, isolated from the kitchen spice turmeric, demonstrates the capability of suppressing, retarding, and even inverting carcinogenesis. It is able to induce apoptosis in cancer cells without cytotoxic effects on healthy cells while inhibiting the formation of tumors. It is well tolerated and is selective for cancer cells. (Lopez-Lazaro. 2008) No definitive dose has been identified, but trials using up to 8,000 mg a day have found no adverse effects. Its particular effectiveness appears to lie in colon cancer lines (Johnson. 2007), but its antiproliferative effects may extend to others (Hanif. 1997) (Lopez-Lazaro. 2008) The military can win a war by cutting off the enemy’s supplies. Could the war on cancer do the same?


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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

What Gets YOU Inflamed?

knee-inflammationAre you an adult? Would you prefer the pound(s) of cure to the ounce of prevention? One of the sad commentaries about adulthood is that we don’t take care of ourselves until something hurts, the detection of which relies on the nervous system. The nervous system is plastic, meaning that it exhibits a wide range of responses according to different conditions. The perception of pain depends on more than one factor, the environment included. With inflammation, however, there exists a hypersensitivity state that makes us aware of what’s going on. This realization is called nociception, involving a network that identifies a noxious condition that evokes responses ranging from mild to severe. Once the pain message is recognized by the nervous system it registers as an “ouch.” The greater the intensity of the stimulus, the greater is the perception of pain. In some cases, no external trigger is needed, such as one would experience with arthritis pain.

Inflammation is the body’s attempt at self-protection, the intention of which is to remove the harmful stimuli, including damaged cells, irritants or pathogens. If the stimulus comes from outside, it can be removed, although pain may linger. If it comes from inside, the body is left to its own devices. In either instance, tissue repair is the ultimate goal. To our dismay, inflammation may beget further inflammation in a self-perpetuating cascade. This occurs because of cellular alterations that cause mediator chemicals to be released and certain white cells, called macrophages, to become activated. The job of the macrophage is to swallow (-phage) the debris that comes from, or causes, tissue damage. Without inflammation, infections and wounds would never heal. In fact, too much anti-inflammatory medication, such as cortisone, slows wound healing (Goforth, 1980). The innate immunity with which we were born is always at the ready to start the inflammatory cascade and to bring healing.

Signs of overt inflammation include pain, redness, immobility (as in loss of function), swelling, and heat (more blood to the area makes it feel warm). Covert inflammation, occurring with internal organs, does not necessarily present with all these signs. Pain arises when swelling pushes on nerves, but sometimes the brain gets used to it and ignores the stimulus. The risk for inflammatory conditions rises with weight gain, as determined by an increase in white blood cells. Regardless of body mass index, C-reactive protein and homocysteine are markers for the presence of inflammatory state, which is at the center of many disorders, from arthritis, through Crohn’s disease, to various allergies and vitamin deficiencies.

Treatment for inflammation abounds in the world of allopathic medicine. Most of us know about NSAIDS, non-steroidal anti-inflammatory drugs, among which Tylenol is not, but aspirin, naproxen and ibuprofen are. Then, there are the corticosteroids—or just plain steroids—that are naturally made by the body in the adrenal glands. But these guys, given as drugs, prevent phospholipid release, and that undermines the activity of eosinophils, which are designed to fight back against allergy, for example, by releasing histamine.

Of the alternative modalities to address inflammation, ginger has accrued quite a following. For hundreds of years it’s been used to treat gastric distress, including dyspepsia and constipation. Recent research points to ginger’s role as an anti-inflammatory agent in the prevention of colon cancer, where inflammation has been identified as a precursor to the disease (Zick, 2011), the markers of which are pro-inflammatory prostaglandins—primarily PGE2—produced by cyclooxygenase (COX) as an early event in the course of the condition (Jiang, 2012).

In a British examination of pain studies, those suffering from osteoarthritis, dysmenorrhea, and acute muscle pain had been administered ginger as the sole treatment. Though additional rigorous trials are anticipated, these subjects reported a reduction in pain, as cited on subjective assessment tools (Terry, 2011). Even before interest in alternative medicine was accelerated to its present status, scientists scrutinized ginger’s reputation in the Ayurvedic community among people treated with the herb for rheumatic concerns, finding efficacy that paralleled traditional interventions (Srivastava, 1989). Applying oral powdered ginger to generalized musculoskeletal discomfort, Danish physicians realized that the safety factor of ginger far exceeded that of any known drugs, while presenting significant efficacy in the relief of pain and swelling via the inhibition of pro-inflammatory prostaglandins (Srivastava, 1992).

By sequestering these incendiary prostaglandins (PG’s), ginger proves itself to be on a par with NSAIDS, minus the concerns of adverse side effects. Similar to prostaglandins in promoting physical aberrations are leukotrienes, products of an enzyme called lipoxygenase (LOX), like COX an offspring of arachidonic acid metabolism. Leukotrienes generally work within the immune system, while PG’s almost always play a role in pure inflammation and pain. (There are beneficent PG’s, by the way.)  Leukotrienes are signaling molecules that call immune cells to the site of infiltration, as from airborne allergens. Bluntly, ginger suppresses the synthesis of leukotrienes (Grzanna, 2005), a property that separates it from NSAIDS. Other of ginger’s attributes point to an anti-oxidant character in the interruption of free radical generation (Ali, 2008), which is helpful in the fight against allergens and pain.

Nitric Oxide (NO) is one of the few signaling gases in the body. The smooth muscle that lines blood vessels is told by NO to relax, thus dilating the vessels and lowering blood pressure. In excessive concentrations, though, NO becomes a pro-oxidant as a naturally unstable free radical, especially when made by white cells (monocytes and macrophages)  during their battle against an infective agent. One logistician that maintains regulation of NO is ginger, where it was shown to control white cell activation as part of its job as an anti-inflammatory vehicle (Shimoda, 2010). Modulating inflammation is what ginger does, and not so gingerly, at that.


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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.