Functional Health Notes 

Copyright Dr. Douglas Husbands.  All material contained herein is original material written and published by Dr. Douglas Husbands.  All rights reserved.

By Dr. Douglas Husbands January 2007
In This Issue
"Therapeutic Lifestyle Progam" classes now available!
Upcoming events and free lectures
New research: Breast cancer news you NEED to know!
Featured Article

According to the National Institutes of Health, Therapeutic Lifestyle Change programs are recommended for fighting obesity, maintaining a healthy body composition, and improving and preventing chronic health conditions.  Join us for the first of our Therapeutic Lifestyle Programs this year...classes are now forming and there is limited registration. 


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"Like apples of gold in settings of silver, is a word spoken in right circumstances."

Poverbs 25:11 

Greetings!

Happy New Year! A new year is a great time to try to improve health habits...In this issue we introduce some programs to help you begin to make improvements and keep you on track!

                               Graciously,

                               Dr. Douglas Husbands

 
Stop the New Year's Weight Loss Resolution Cycle: Make Therapeutic Lifestyle Changes! 

After splurging through the Thanksgiving, Christmas and New Years holidays, many of us find our bodies heavier and our pocketbooks lighter. 

Many people make yearly resolutions to "loose weight" and often accomplish that temporarily...then gain it back, and more, before the year is out.  Additionally, many people loose weight, but many times the weight loss is a mostly a loss of muscle and a only a little fat.  That is a recipe for not only steady fat gain, but also initiation of processes leading to chronic diseases, according to research from the scientific literature.  In fact stopping this cycle and prevention of steady fat gain and muscle loss can prevent many chronic disease according to articles from the journal Diabetes, and the Journal of Applied Physiology.

Rather than weight loss programs, the National Institutes of Health recommends "Therapeutic Lifestyle Changes" for losing bodyfat while maintaining or gaining muscle.  We are having the first of our Therapeutic Lifestyle Programs classes beginning in mid to late January...to help you make permanent changes for improved body composition...for now and for a lifetime!

Register now to join Dr. Husbands and others at our office in San Carlos on Wednesday evenings from 6:30-7:30 for this fun, informative and effective 12 week program.  For the cost of a daily Starbucks and a fast food value meal, you can effectively change harmful habits to healthful habits and significantly improve your figure and your health. Click on additional details and class information. Join with a friend for additional camaraderie and accountability!

  

Upcoming Events and Lectures

Does the picture above showing intracellular signaling make no sense or seem boring to you? Does it sound like your doctor is speaking Klingon when they've explained to you about your health condition?

Take the opportunity to learn about the practical application of latest health research information in a fun, entertaining and interesting way with Dr. Husbands and to ask questions.  Because many patients often have more questions than time allows during an office visit, these forums in various locations are your chance to learn more about various health topics of interest.  Additional lectures will be updated in our website in upcoming events throughout the year, so check back at least once a month for additional lectures and presentations.

If you miss a presentation you wished to attend, check in articles in our website, for some presentations are posted there.

 New research gives breast cancer info. you NEED to know

On December 15th, 2006 all of the major news links reported a story with profound implications: A new study reveals that U.S. breast cancer rates plunged more than 7 percent in 2003 and strongly suggests that the reason is less artificial-hormone use. This equates to approximately 14,000 women that did not get breast cancer apparently as a result of not using the previously commonly prescribed drugs premarin and provera.


The study findings were reported at the San Antonio Breast Cancer Symposium(1) on December 14th by researchers from the University of Texas MD Anderson Cancer Center, the National Cancer Institute and the Harbor UCLA Medical Center. 


The implications of this is phenomenal: How many women did contract and die from breast cancer as a result of the use of the synthetic hormone replacement therapy drugs over the many years which they were commonly prescribed?  More importantly:


1. What factors can women take to decrease their risk of  developing breast cancer?...and
2. Are there treatment options that work more gently and effectively than conventional treatment?

Options with Breast Cancer
Clearly with the preponderance of research and clinical evidence, there is a significantly increased risk of breast cancer (and other cancers and diseases for that matter) associated with the use of synthetic hormones in women (2-9).
Therefore, besides cessation of synthetic hormones for prevention and treatment of breast cancer, there are other options.  From a functional medicine viewpoint, we can look at four particular aspects which, according to the research, can synergistically contribute towards decreased breast cancer risk and can be used as potential modalities for breast cancer treatment. These four particular aspects are:


1. Nutrients as biologic response modifiers (BRM's) 
2. Reduce environmental toxic load with enhanced detoxification
3. Exercise as a positive immune response mechanism
4. Structural balancing synergistic effects on biochemical and neuroendocrine modulation

We will look at a couple of promising nutrients as BRM's in this newsletter article.

Nutrients as biologic response modifiers
A biologic response modifier is a term recently used in conventional medicine typically reserved for drugs which influence immune responses.  However, the term "biologic response modifier" is exquisitely appropriate to describe the effect nutrients have on multiple responses in human physiology.  Used in this context, this author will use the term with the following definition: A biologic response modifier (BRM's) is a substance found in plants or naturally occurring in foods commonly consumed by humans which have beneficial immune modulating and genetic expression modification effects. 


Many nutrients act as biologic response modifiers with powerful effects on health and disease processes.  As BRM's, foods and specific nutrient substances and analogs used in therapeutic dosages can significantly influence immune responses and modify genetic expression of disease (10).  Research shows there are very powerful nutrient substances that when used in therapeutic dosages, have a significant influence on the etiology of breast cancer.  Two of these substances are indole-3-carbinol, and resveratrol.

Indole-3-carbinol
Indole-3-cabinol (I3C) is a compound found in high concentrations in the Brassica family vegetables, including broccoli, cauliflower, brussels sprouts, cabbage and kale. It has relatively recently become available in nutritional supplement form.  I3C has been shown to inhibit growth of breast cancer cells by several in vitro and in vivo mechanisms. (in vitro = studies conducted in test tubes; in vivo= studies conducted in animals or humans)

Several studies have shown I3C to inhibit the growth of estrogen receptor-positive and estrogen receptor-negative breast cancer cells(11,12).  I3C has been shown to work separately or cooperatively with tamoxifen by a different mechanism.

I3C also inhibits estrogenic activity by competing with estrogen for estrogen receptor binding sites on the cell(13).

A metabolite of I3C, diindolylmethane (DIM), has been shown to induce cytochrome p450 isoenzymes (14,15) .  Cytochome p450 induction by DIM modulates (modulate: to adjust to or keep in proper measure) estrogen activity.

I3C inhibits the ability of human breast cancer cells to metastasize (16).


I3C blocks estrogenic stimulation of human papilloma virus (HPV) expression (17).  HPV is implicated in the pathogenesis of cervical cancer, and also head and neck cancers.


I3C also increases the "beneficial" estrogen metabolites" and decreases the "harmful" estrogen metabolites. Many research studies show that the pathways by which estrogen is metabolized is an important etiological factor in diseases such as breast cancer, uterine, ovarian, cervical and even head and neck cancers (18-21).  To briefly explain: Estradiol undergoes oxidative conversion to estrone.  Estradiol and estrone can undergo hydroxylation by different isoenzymes...either at the 2 or 16 carbon atoms. These different metabolites have opposing effects on estrogen receptors: The 16-hydroxyestrone metabolites are associated with cancer cell proliferative effects where the 2-hydroxyestrone metabolites are associated with antiproliferative effects on cancer cells. Research shows statistically significant decreased risk for uterine, ovarian and cervical cancers in women with higher ratios of 2 to 16 hydroxyestrones.   The anti-carcinogenic 2-hydroxyestrones are increased and the pro-carcinogenic 16-hydroxyestrones are decreased, respectively, by I3C (22,23).

This effect has been verified in many patients by this author through a special laboratory test of urine.  We have seen this effect occur in as rapidly as 60 days in many patients. The therapeutic dose range of I3C is between 200-400 mg/day, though studies show safety even at higher dosages.


Resveratrol
Resveratrol is a phenolic antioxidant found in grapes, and can be isolated for supplemental use.  Resveratrol in nutraceutical dosages inhibits the activity of COX-2 inflammatory enzymes in human breast and oral epithelial cells (24). A preponderance of research implicates inflammation as an underlying etiology in many diseases, including cancer.


Resveratrol also inhibits an enzyme which is critical in the conversion of androgens to estrogens (25).  This enzyme, called the cytochrome P450 (CYP) 19, or aromatase, shows elevation in over 60% of breast carcinomas (26)  with higher levels of messenger RNA expression and activity compared with non-malignant tissue (27).  This mechanism by which therapeutic doses of resveratrol inhibits aromatase at both the enzyme and messenger RNA levels is significant in decreasing the risk, or use as adjunctive treatment, in breast cancer.

Resveratrol also has activity as an adaptogen. Simply stated, an adaptogen is a substance which raises the production of a chemical the body produces when it's too low, or lowers the production of a chemical the body produces when it's too high.  Resveratrol has an adaptogenic effect on estrogen activity (28).  Studies in humans have shown it produces an anti-estrogenic effect in endometrial cancers (29).

In this newletter, this author has briefly reviewed two nutrients which research confirms has powerful effects towards breast cancer reduction risk and may be useful in treatment.  Used judiciously with other synergistic nutrient substances, lifestyle modifications and dietary factors, this is an option to be considered for modifying breast cancer outcomes.

 References 

1. Ravdin, PM, Cronin, KA, Howlander, N, Chlebowski, RT, Berry, DA.  A sharp decrease in breast cancer incidence in the United States in 2003. Presentation of research findings at the 29th Annual Breast Cancer Symposium, Dec. 14 2006.
 2. Risks and benefits of estrogen plus progestin in healthy postmenopausal women, JAMA 2002;288:321-33.
3. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women, JAMA 2003;289:3243-53.
4. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women, JAMA 2003;289:2651-62.
5.  Estrogen carcinogenesis in breast cancer, NEJM 2006;354:270-282.
6. Short-term biologic response to withdrawal of hormone replacement therapy in patients with invasive breast carcinoma, Cancer. 2003;98:2539-2546.
7. Cardiovascular disease outcomes during 6.8 years of hormone therapy, JAMA, 2002;288:49-57
8. Menopausal hormone replacement therapy and risk of ovarian cancer JAMA, 2002;288:334-41.
9. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003;362:419-27.
10. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased Km): relevance to genetic disease and polymorphisms, AJCN, 2002:75;616-58.
11. Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res 1999;59:1244-51.
12. Inhibition of proliferation and modulation of estradiol metabolism: novel mechanisms for breast cancer prevention by the phytochemical indole-3-carbinol Proc Soc Exp Biol Med 1997;216:246-52.
13. Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res 1999;19:1673-80.
14. Structural elucidation of acid reaction products of indole-3-carbinol: detection in vivo and enzyme induction in vitro. Chem Biol Interact 1991;80:303-15.
15. The micronutrient indole-3-carbinol: implications for disease and chemoprevention. Drug Metabol Drug Interact 2000;17:159-88.
16. Inhibitory effects of indole-3-carbinol on invasion and migration in human breast cancer cells. Breast Cancer Res Treat 2000;63:147-52.
17. Anti-estrogenic activity of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res 1999;19:1673-80.
18. Antiestrogen action of 2-hydroxystrone on MCF-7 human breast cancer cells. J Biol Chem 1984;259:4840-45.
19. A pilot study of urinary estrogen metabolites (16?-OHE1 and 2-OHE1) in postmenopausal women with and without breast cancer.  Environmental Health Perspectives. 1998;106:A126-A127.
20. Estrogen metabolite ratios and risk assessment of hormone-related cancers. Assay validation and prediction of cervical cancer risk. Ann N Y Acad Sci 1995;768:312-16.
21. Estrogen metabolism as a risk factor for head and neck cancer. Otolaryngol Head Neck Surg. 2001;124:241-47.
22. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J CellBiochem Suppl 1997;28-29:111-16.
23. Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev 1994;3:591-5.
24. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J. Biol Chem 1998;273:21875-82.
25. The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells. Toxicological Sci. 2006;92:71-7.
26. Aromatase activity in breast tissue. J Steriod Biochem Molecular Biol. 1991; 39: 783-90.
27. A link between breast cancer and local oestrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clinical Endocrinol Metabolism. 1993;77:1622-28.
28. Estrogenic and antiestrogenic properties of resveratrol in mammary tumore models. Cancer Res. 2001;61:7456-63.
29. Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (Ishikawa) cells. Cancer Res. 2001;61:6137-44.