March 31, 2003 Research Update

James Bogash, D.C. Mesa, AZ
info@lifecarechiropractic.com
www.lifecarechiropractic.com

The Relative Safety of Ephedra Compared with Other Herbal Products

Alright, while I rarely recommend ephedra containing products in my office, I need to speak up on this issue. First of all, ephedra products are greatly overused and the potential for abuse is high. But, in all, there have been maybe 20 deaths associated with ephedra over its recorded history. Not to minimize 20 deaths, but Tylenol kills that many in a month, let alone over it's recorded history and yet no one is screaming for Tylenol to be pulled from the shelves. Make no mistake--the attack on ephreda is only the beginning of a slippery slope to make supplements prescription items to be prescribe only by doctors who have little or no training in these products.

Annals of Internal Medicine: Abstract

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NSAIDs as a Trigger of Clinical Heart Failure

NSAIDs double the risk of heart failure in patients with a history of heart problems. Considering their widespread use, the number of patients affected by this association is probably close to staggering. All by themselves, NSAIDs are believed to cause some 16-19,000 deaths per year via GI bleeding (kind of beats 20 over a lifetime, huh?).

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Plasma oxidized LDL: a predictor for acute myocardial infarction?

Remember that LDL cholesterol itself does not do damage to the body until it gets damaged itself through oxidation (sometimes termed oxysterols). Here we see the development of yet another tool to assess heart disease risk. Keep in mind that, even with high cholesterol, high intakes of antioxidants can serve to protect the LDL particle from being damaged.

Synergy Abstract

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Amino Acids Strongly Enhances Insulin Secretion in Type 2 DM

In patients with diabetes, the pancreas begin to putter out and ultimately produces less and less insulin (as opposed to syndrome X, where hyperinsulinemia is the damaging force). Many diabetic drugs are designed to force the pancreas to produce more insulin. Here we see that certain amino acids can have the same effects, thus giving dietary recommendations a strong therapeutic potential for treatment of diabetes. What is interesting is that the insulin response was strongest in a specific amino acid preparation along with a carbohydrate meal. This also puts a wrench in the works for those that say high protein diets work by lowering the body's response to insulin.

Dia Care -- Abstracts: van Loon et al. 26 (3): 625

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Blood Lead, BP, and Hypertension

Heavy metals are widely overlooked by mainstream medicine despite heavy research into their affects on human health. Here we see links with hypertension. Of additional note on BP is cadmium (found mainly in cigarette smoke) which damages the kidneys and can lead to hypertension.

JAMA -- Abstracts: Nash et al. 289 (12): 1523

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Magnesium, phospholipid and energy metabolism between migraine syndromes

I found it very interesting when one of my patients with seizures consulted an ER doctor friend of hers about her seizures. He basically informed her that she needed to be on antiseizure medication (with a standing order for bloodwork to check liver enzymes every two weeks...) and nothing else had any effect. Apparently he hasn't cracked a medical journal in several years, and sadly, when doctors display their ignorance on subjects they are not educated in it confuses patients and can compromise their adherence to recommendations. In this article we see that magnesium has an effect on hyperexitability of the cortex. This article relates these findings to the aura of a migraine, which is essentially seizure activity.

Synergy Abstract

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Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer

This article is interesting given the fact that men with history of prostate cancer and women with history of breast cancer are told to avoid soy products. However, the evidence seems to support the fact that soy compounds are not only non-harmful, but possibly show a benefit.

AJCN -- Abstracts: Miltyk et al. 77 (4): 875

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Saw Palmetto for Prostate Disorders

American Family Physician has been putting out some nice articles on natural products that are fair and well-balanced. Here we see further support for the use of saw palmetto for prostate enlargement. I would add to this mix lycopene (the red carotenoid that gives tomatos and watermelo their color) and cruciferous veggies (see below...) for further prostate health.

Saw Palmetto for Prostate Disorders - March 15, 2003 - American Family Physician

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2-Methoxyestradiol, a Promising Anticancer Agent

It is very interesting that researchers are viewing this compound as a potential anti cancer compound. Past issues of the Updates have reviewed the concept that estrogens are broken down by several pathways in the body, primary of which are the 16-, 4- and 2-hydroxyestradiol. The 16 pathway is well demonstrated to be genotoxic while the 2 pathway is protective. The 2/16 ratio (which is easily checked in urine or serum) has been linked with several types of cancer, including prostate, breast, endometrial and throat. The wonderful thing about this ratio is that it is modifyable by indole-3-carbinol in cruciferous veggies (unless of course you are on acid-suppressive therapy because stomach acid is needed to activate the compound from foods).

Pharmacotherapy 23(2):165-172, 2003

Estrogens occurring naturally in the body are metabolized to catecholestrogens (2- and 4-hydroxyestradiol) by the cytochrome P450 enzymes. 2-Hydroxy catecholestrogens are further metabolized by catechol-O-methyltransferase to 2-methoxyestradiol, which is known to be protective against tumor formation. 2-Methoxyestradiol exhibits potent apoptotic activity against rapidly growing tumor cells. It also possesses antiangiogenic activity through a direct apoptotic effect on endothelial cells. Other molecular mechanisms, including microtubule stabilization by inhibition of the colchicine-binding site, have been reported. The exact mechanism of action of 2-methoxyestradiol is still unclear, but it has been shown to be effective in preventing tumor growth in a variety of cell lines. 2-Methoxyestradiol also possesses cardioprotective activity by inhibiting vascular smooth muscle cell growth in arteries. It has a lower binding affinity for estrogen receptor alpha compared with that of estradiol, and its affinity for estrogen receptor-beta is even lower than that of estrogen receptor alpha, thus it has minimal estrogenic activity. 2-Methoxyestradiol is distinct because of its inability to engage estrogen receptors as an agonist, and its unique antiproliferative and apoptotic activities are mediated independently of estrogen receptors alpha and beta. A phase I clinical trial of 2-methoxyestradiol 200, 400, 600, 800, and 1000 mg/day in 15 patients with breast cancer showed significant reduction in bone pain and analgesic intake in some patients, with no significant adverse effects. Another phase I study of 2-methoxyestradiol 200-1000 mg/day in combination with docetaxel 35 mg/m2/week for 4-6 weeks performed in 15 patients with advanced refractory metastatic breast cancer showed no serious drug-related adverse effects. A phase II randomized, double-blind trial of 2-methoxyestradiol 400 and 1200 mg/day in 33 patients with hormone-refractory prostate cancer showed that it was well tolerated and showed prostate specific antigen stabilizations and declines. We have started a phase I clinical trial to explore dosages greater than 1000 mg/day.

Nutrition in Crohn Disease-Butyrate

Butyrate is a short chain fatty acid produces when healthy bacterial flora digest soluble fiber. Butyrate has long been shown to be effective with many GI disorders because it is the preferred fuel source for the cells lining the colon.

Curr Opin Gastroenterol 19(2):148-153, 2003

Butyrate is a short-chain fatty acid produced by bacterial fermentation of dietary fiber and undigested starch in the colon. It is important in maintaining the health and integrity of colonic mucosa,[55] as it provides greater than 70% of the energy supply of the colonocyte.[56] Recently, it was demonstrated that butyrate inhibits the inflammatory response in CD by inhibiting the transcription factor nuclear factor kappa B (NFkappaB) activation in immune cells.[57] NFkappaB is involved in inflammatory and immune responses and regulates TNF. By inhibiting NFkappaB, TNF is downregulated and, theoretically, inflammation will be reduced. Already demonstrated in patients with steroid-resistant CD is marked improvement in those patients treated with monoclonal antibodies to TNF.[58] Although further studies are needed to determine the best method of administering butyrate, it offers promise for an immune modulatory therapy for treating patients with CD. Of note, an oral precursor of butyrate has recently been used in ulcerative colitis and was successful in lowering corticosteroid dose. Further utility in CD might be of special interest.