Highlight HEALTH

As 2007 comes to a close, I would like to thank you for your readership. Just over one year ago, I launched two websites, Highlight HEALTH and the Highlight HEALTH Web Directory. Here at Highlight HEALTH, my goal was to write about biomedical research I found interesting and to make it easier for people to understand research findings, empowering them to have more productive discussions with their physicians and to make informed decisions about healthcare. The Highlight HEALTH Web Directory is my endeavor to catalog and make available health-related websites I find to be informative and useful. More recently, I’ve also started writing about Web 2.0 in Health, Fitness and Medicine, and plan to publish a series of review articles on a number of health-focused social networks.

This past month, I started the Highlight HEALTH Network, an aggregation of content from both sites to allow readers to keep up with the latest articles on Highlight HEALTH and the newest additions to the Highlight HEALTH Web Directory, all from a single source.

Here are the most popular articles for 2007 (top 20 based on the number of page views/number of days posted):

1. The Highlight HEALTH Network RSS Dashboard Widget
2. Smoking Cessation Timeline: What Happens When You Quit
3. Dichloroacetate Not Ready for Therapeutic Use
4. The Highlight HEALTH Network
5. New Common Cold Virus Variant Deadly
6. Common Therapy for Prostate Cancer May Promote Metastasis
7. Overweight Kids and TV: An Advertising Epidemic
8. Saline Nasal Irrigation More Effective than Spray for Chronic Sinus Symptoms
9. Pediatric Grand Rounds 2.8
10. The Genetics of Panic Disorder
11. Smoking Duration vs. Intensity and the Impact on Lung Cancer Risk
12. Social Networks and Health - The Research and the Reviews
13. Quercetin
14. American Obesity Rate Levels Off
15. Biodegradable Polymers for Drug and Gene Delivery
16. Individual Genetics, Coffee Consumption, BRCA1 and Breast Cancer
17. The Flu, Your Health and the Importance of Vaccination
18. SCHIP Funding and Fiscal Irresponsibility
19. DNA Amplification by Polymerase Chain Reaction (PCR)
20. Sinus Congestion

Thank you and Best of Health in the coming year!

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In February 2007, researchers at Appalachian State University announced the results of a clinical study on the flavonoid quercetin at the Southeastern Regional Meeting of the American College of Sports Medicine, held in Charlotte, N.C. Their results showed that quercetin may help reduce illness and maintain mental performance in physcially stressed test subjects. I’ve written about the antioxidant quercetin in a previous article as an alternative to dichloroacetate (DCA), a chemotherapeutic agent that was recently shown to selectively inhibit cancer cell growth in lung, breast and brain tumor cells grown in culture and lung tumors grown in immunocompromisted rats.

In December 2005, the Defense Advanced Research Projects Agency (DARPA) awarded Appalachian State University 1.1 million to fund a two-year study of the effects of quercetin [1]. DARPA is seeking ways to maintain troop immune systems during times of physical and cognitive stress. Dr. David Nieman is the principal investigator of the study and a professor in the Department of Health, Leisure and Exercise Science at Appalachian State University. He has been investigating the influence of exercise and nutrition on the immmune system for the last 23 years.

The double-blind, randomized, placebo-controlled study provided 1,000 mg/day of high-purity quercetin, a polyphenol, plus niacin and vitamin C to aid in absorption, to 20 trained cyclists for five weeks. A second group of 20 cyclists received a placebo. Three weeks into the study, participants rode a bicycle to the point of exhaustion three hours per day for three days. Blood and tissue samples were collected and analyzed to track any physicological changes that occurred.

Only 5% of the group that received quercetin reported illness after being physically stressed, compared with 45% of the participants who received placebo. No adverse side effects were observed. Surprisingly, the immune-boosting properties of quercetin weren’t readily observable until after the three-day intense exercise period. Additionally, when given an alertness test, those participants that were given quercetin better maintained their ability to react after exhaustion.

Said Dr. Nieman [2]:

It appears that it takes significant stress to bring out quercetin’s infection-fighting properties. This all happened when athletes were under high oxidative stress, when stress hormones were high, and they were also undergoing muscle damage.

Nieman plans a follow-up study to see if quercetin has any benefits for people who are undergoing everyday mental stress.

More about quercetin can be found in these posts:

• Quercetin
• Alternative to Dichloroacetate

References

1. Defense Dept Funds $1.1 Million for Research. The College of Fine & Applied Arts, Appalicain State University. 2005 Dec 7.
2. Research at Appalachian State Indicates Natural Plant Substance Helps Reduce Illness in Physically Stressed Athletes; Findings May Have Military Application. Appalachian State University News. 2007 Feb 8.
3. Sampson et al. Flavonol and flavone intakes in US health professionals. J Am Diet Assoc. 2002 Oct;102(10):1414-20.
   View abstract

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It’s been three months since an article on dichloroacetate (DCA), the chemotherapeutic agent that selectively inhibits cancer cell growth in lung, breast and brain tumor cells grown in culture and lung tumors grown in immunocompromised rats, was published on Highlight HEALTH. Since then, thousands of people have read the article. Indeed, the blogosphere has been buzzing about DCA, unfortunately focusing on a conspiracy theory accusing big pharma of suppressing a cure for cancer instead of recognizing the study for what it is — a preliminary study in cell culture and rats that cannot be translated to humans without further research and clinical trials.

Safe alternative to DCA?

I was curious to see if there were any new developments regarding DCA use in either cancer prevention or the treatment of cancer. A Google search for “dichloroacetate” returned 340,000 pages, but before I had a chance to start browsing, one of the Sponsored Links at the top of the page caught my eye. In addition to a site where you can buy DCA, another site advertised a “safe alternative” to dichloroacetate.

Intrigued, I clicked on the link. The alternative is a “new flavonoid cancer treatment protocol”, which involves nothing more than dissolving 1000 mg of vitamin C in 0.5 L of water and adding the contents of 1 — 2 quercetin (pronounced “kwer-see-tin”) capsules (500 mg — 1000 mg).

Quercetin

A polyphenol, quercetin is one of a number of water-soluble plant pigments called flavonoids (meaning class of plant secondary metabolites known for their antioxidant activity) and is largely responsible for the color of many flowers, fruits and vegetables. High concentrations of quercetin are found in apples, onions, tea and red wine [1]. Quercetin and other flavonoids (also referred to as bioflavonoids) cannot be produced in the human body.

Quercetin is a powerful antioxidant; from a range of dietary flavonoids, quercetin was found to be the most effective inhibitor of oxidative damage to LDL (bad) cholesterol in vitro [2]. In contrast, another study found that quercetin had mostly prooxidant effects [3]. However, when mixed with other phenolic compounds, significant antioxidant capacity was identified, indicating a synergistic effect.

A number of research studies have demonstrated that quercetin is a natural antihistamine and anti-inflammatory [4-6]. Indeed, quercetin is unique in its ability to inhibit TNF-alpha (a cytokine involved in systemic inflammation) gene expression [7]. Studies have also shown that quercetin exhibits anticancer effects [8].

Clinical trials

A number of phase I clinical trials have been performed with quercetin evaluating pharmacokinetics [9] and adenoma regression [10]. A combination of curcumin and quercetin was evaluated to regress adenomas in patients with familialadenomatous polyposis (FAP), an autosomal-dominant disorder characterized by the development of colorectal adenomas and eventual colorectal cancer. The study found that the combination appeared to decreased polyp number and size from baseline after 6 months of treatment [10].

Epidemiologic data indicates that reduction in colorectal cancer risk associated with the highest 25% of data vs. the lowest 25% was largest for quercetin and catechin [11]. Overall, flavonoids showed strong and linear inverse associations with colorectal cancer risk. Large-scale genomic studies in colon cancer cells suggest that quercetin affects the expression of genes involved in cell cycle control [12-13]. Flavonoids also modulate cell cycle progression in prostate cancer cells [14-15].

Antioxidants and cancer

In September 2005, an article published in CA: A Cancer Journal for Clinicians warned against the use of antioxidants in combination with radiotherapy and chemotherapy [16]. Indeed, quercetin may alter the effects of chemotherapy medications used to treat cancer [17]. However, this position has been refuted by others [18] and a recent meta-analysis suggests that antioxidant supplementation does not interfere with therapeutic modalities for cancer and instead enhances the killing of therapeutic cancer agents, decreases modality side effects and protects normal tissue [19-20]. Another meta-analysis reviewing the evidence from randomized controlled trials on the impact of antioxidant supplementation on chemotherapeutic efficacy, although limited by lack of statistical power, found that many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumor responses or both, as well as fewer toxicities than controls [21].

A recent review assessing the contribution of dietary flavonoids to the total antioxidant capacity of plasma in humans concluded that the large increase in plasma total antioxidant capacity observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, but is likely the consequence of increased uric acid levels [22]. A potent antioxidant, uric acid is a normal constituent of the body and is the end product of purine (meaning the nucleotides adenine and guanine, two of the four building blocks of RNA and DNA) metabolism. Because the increased plasma concentration of uric acid is much greater than the concentration of flavonoids, the change in uric acid levels is thought to be responsible for the relatively large increase in plasma total antioxidant capacity after consumption of flavonoid-rich foods. Most uric acid produced in the body is excreted by the kidneys. However, it has been proposed that renal uric acid clearance is regulated by an unknown signal that is issued in response to the level of oxidative stress [23], allowing the kidneys to reabsorb the potent antioxidant when needed.

Flavonoids have been shown to induce detoxifying Phase II enzymes [24-25], indicating that they are recognized by the body as foreign compounds. Thus, it has been proposed that the ability of flavonoids to induce detoxifying enzymes may be a major mechanism by which flavonoids protect against mutagens and carcinogens, and act as cancer chemopreventive agents [22].

References

1. Sampson et al. Flavonol and flavone intakes in US health professionals. J Am Diet Assoc. 2002 Oct;102(10):1414-20.
   View abstract
2. O’Reilly et al. Flavonoids protect against oxidative damage to LDL in vitro: use in selection of a flavonoid rich diet and relevance to LDL oxidation resistance ex vivo? Free Radic Res. 2000 Oct;33(4):419-26.
   View abstract
3. Cirico and Omaye. Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation. Food Chem Toxicol. 2006 Apr;44(4):510-6. Epub 2005 Oct 10.
   View abstract
4. Middleton and Drzewiecki. Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem Pharmacol. 1984 Nov 1;33(21):3333-8.
   View abstract
5. Taguchi et al. Pharmacological studies of Houttuyniae herba: the anti-inflammatory effect of quercitrin. Yakugaku Zasshi. 1993 Apr;113(4):327-33.
   View abstract
6. Loggia Della et al. Anti-inflammatory Activity of Benzopyrones that are Inhibitors of Cyclo- and Lipo-oxygenase. Pharmacol Res Commun. 1988 Dec;20 Suppl 5:91-4.
   View abstract
7. Wadsworth et al. Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha. Biochem Pharmacol. 2001 Oct 1;62(7):963-74.
   View abstract
8. Morrow et al. Dietary supplementation with the anti-tumour promoter quercetin: its effects on matrix metalloproteinase gene regulation. Mutat Res. 2001 Sep 1;480-481:269-76.
   View abstract
9. Ferry et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res. 1996 Apr;2(4):659-68.
   View abstract
10. Cruz-Correa et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006 Aug;4(8):1035-8. Epub 2006 Jun 6.
    View abstract
11. Theodoratou et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):684-93.
    View abstract
12. van Erk et al. Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. Epub 2004 Apr 30.
    View abstract
13. Murtaza et al. A preliminary investigation demonstrating the effect of quercetin on the expression of genes related to cell-cycle arrest, apoptosis and xenobiotic metabolism in human CO115 colon-adenocarcinoma cells using DNA microarray. Biotechnol Appl Biochem. 2006 Jul;45(Pt 1):29-36.
    View abstract
14. Kobayashi et al. Effect of flavonoids on cell cycle progression in prostate cancer cells. Cancer Lett. 2002 Feb 8;176(1):17-23.
    View abstract
15. Knowles et al. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer. 2000;38(1):116-22.
    View abstract
16. D’Andrea GM. Use of antioxidants during chemotherapy and radiotherapy should be avoided. CA Cancer J Clin. 2005 Sep-Oct;55(5):319-21.
    View abstract
17. Desai et al. Human liver microsomal metabolism of paclitaxel and drug interactions. Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):417-24.
    View abstract
18. Moss RW. Should patients undergoing chemotherapy and radiotherapy be prescribed antioxidants? Integr Cancer Ther. 2006 Mar;5(1):63-82.
    View abstract
19. Simone et al. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1. Altern Ther Health Med. 2007 Jan-Feb;13(1):22-8.
    View abstract
20. Simone et al. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, Part 2. Altern Ther Health Med. 2007 Mar-Apr;13(2):40-7.
    View abstract
21. Block et al. Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev. 2007 Mar 14; [Epub ahead of print].
    View abstract
22. Lotito and Frei. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free Radic Biol Med. 2006 Dec 15;41(12):1727-46. Epub 2006 Jun 3.
    View abstract
23. Kirschbaum B. Renal regulation of plasma total antioxidant capacity. Med Hypotheses. 2001 Jun;56(6):625-9.
    View abstract
24. Kong et al. Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE). Drug Metab Rev. 2001 Aug-Nov;33(3-4):255-71.
    View abstract
25. Walle and Walle. Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements. Drug Metab Dispos. 2002 May;30(5):564-9.
    View abstract

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