Recent Longevity News for the seven days ending 4/9/08.  You should consult your doctor if you are taking any medications.

Green Tea Ingredient, EGCG, Significantly Inhibits Breast Cancer Growth In Female Mice - Science Daily, 4/7/08 - "Green tea is high in the antioxidant EGCG (epigallocatechin-3- gallate) which helps prevent the body’s cells from becoming damaged and prematurely aged ... At the end of the five week period the researchers found that oral consumption of EGCG caused significant decreases in TCSA (66%), tumor weight (68%), IM density 155+/-6 vs.111+/-20 IM#mm^2) and VEGF protein levels (59.0+/-3.7 vs. 45.7+/-1.4 pg/mg) in the breast tumors vs. the control mice, respectively (N=8; P<0.01). Further, VEGF plasma levels were lower in EGCG mice than in control mice (40.8+/-3.5 vs. 26.5+/-3.8 pg/ml P< 0.01)"  - [WebMD] - See green tea extract at Amazon.com.

Omega-3 EPA may benefit depressives, says study - Nutra USA, 4/7/08 - [Abstract] - "were randomly assigned to receive a daily EPA supplement (1000 mg, supplied by Minami Nutrition, Belgium), or 20 mg fluoxetine daily, or a combination of the two for two months ... At the end of the study, data from the 48 people who finished the study showed a 50 per cent reduction in HDRS scores for people in the EPA group, a 56 per cent reduction in people in the fluoxetin group, and a 81 per cent reduction in people in the combined intervention group" - See Mega Twin EPA at iHerb.

Testosterone Replacement Theraphy Beneficial In Men 60 And Older, Study Suggests - Science Daily, 4/7/08 - "These preliminary data show beneficial effects of testosterone therapy on bone turnover markers in older men with low-to-normal testosterone concentrations using both continuous and monthly cycled testosterone replacement"

Red Wine, Tea, May Help Regulate Blood Sugar In Type 2 Diabetics, Research Suggests - Science Daily, 4/2/08 - "Both red and white wines were tested in the laboratory using in vitro enzyme studies to determine how well they could inhibit the activity of a target enzyme called alpha-glucosidase, responsible for triggering the absorption of glucose by the small intestine. Red wine was the winner, able to inhibit the enzyme by nearly 100 percent. Values for white wine hovered around 20 percent ... red wine contains roughly ten times more polyphenolics than white wine"

Pioglitazone May Prevent Progression of Atherosclerosis in Patients With Type 2 Diabetes - Doctor's Guide, 4/2/08 - "Two TZD agents are currently on the market -- pioglitazone and rosiglitazone. Both agents reduce inflammatory biomarkers, while pioglitazone also produces elevation of high-density lipoprotein cholesterol (HDL-C) and reduction of triglyceride levels ... Dr. Nissen said the findings of the PERISCOPE study support the conclusion that treatment with pioglitazone can prevent the progression of atherosclerosis in patients with type 2 diabetes during 18 months of treatment. These finding may have important implications for defining the optimal strategy for management of patients with type 2 diabetes and coronary atherosclerosis" - See pioglitazone at OffshoreRx1.com.

Cup Of Coffee A Day Could Help Protect Against Alzheimer's Disease, Study Suggests - Science Daily, 4/2/08 - "Caffeine appears to block several of the disruptive effects of cholesterol that make the blood-brain barrier leaky ... High levels of cholesterol are a risk factor for Alzheimer's disease, perhaps by compromising the protective nature of the blood-brain barrier. For the first time we have shown that chronic ingestion of caffeine protects the BBB from cholesterol-induced leakage"

Abstracts from this week's Doctor's Guide Nutrition/Dietetics plus abstracts from my RSS feeds (Click here for the journals, the PubMed ones at the top):

Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells - Int J Cancer. 2008 Apr 3 - "Interestingly, curcumin caused cell cycle arrest in G2-M and a significant reduction (80-97%) in H-RS cell viability. Furthermore, curcumin triggered cell death by apoptosis, as evidenced by the activation of caspase-3 and caspase-9, changes in nuclear morphology and phosphatidylserine translocation. The above findings provide a mechanistic rationale for the potential use of curcumin as a therapeutic agent for patients with HL" - See curcumin products at Amazon.com.

Effect of Rosiglitazone on Cardiac Fibroblast Proliferation, Nitric Oxide Production and Connective Tissue Growth Factor Expression Induced by Advanced Glycation End-products - J Int Med Res. 2008 Mar-Apr;36(2):329-35 - "AGEs significantly accelerated proliferation, increased CTGF expression and decreased nitric oxide production in cardiac fibroblasts. These effects of AGEs were inhibited by RGZ in a dose-dependent manner" - Note:  AGEs were the main reason I have been taking thiazolidinediones.  I've switched from rosiglitazone to pioglitazone though.  See pioglitazone at OffshoreRx1.com.

Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced Glycation End-product (AGE)-elicited Hepatic Insulin Resistance via Peroxisome Proliferator-activated Receptor-gamma Activation - J Int Med Res. 2008 Mar-Apr;36(2):237-43 - "Candesartan, another ARB, did not affect AGEs-induced serine phosphorylation of IRS-1 at serine-307 residues in Hep3B cells. Our study suggests that telmisartan could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting serine phosphorylation of IRS-1, at least in part, via activation of PPAR-gamma" - Note:  That might be another reason for considering telmisartan as a first line treatment for hypertension.  See telmisartan at OffshoreRx1.com.

Effects of niacin on glucose control in patients with dyslipidemia - Mayo Clin Proc. 2008 Apr;83(4):470-8 - "the effects of niacin (</=2.5 g/d), alone or in combination with statins, on fasting glucose (an increase of 4%-5%) and hemoglobin A1c levels (an increase of </=0.3%) are modest, transient or reversible, and typically amenable to adjustments in oral hypoglycemic regimens without discontinuing niacin. Niacin therapy was infrequently associated with incident diabetes or the need for new insulin prescriptions. Studies showed important clinical benefits of niacin or niacin-statin regimens despite modest effects on glucose control. On a population basis, significant reductions in incidences of cardiovascular events and the degree of atherosclerotic progression associated with long-term niacin (or niacin-statin) therapy in patients with diabetic dyslipidemia outweigh the typically mild effects of this therapy on glycemic regulation"

Omega-3 Fatty Acids for Major Depressive Disorder During Pregnancy: Results From a Randomized, Double-Blind, Placebo-Controlled Trial - J Clin Psychiatry. 2008 Mar 18;:e1-e8 - "As compared to the placebo group, subjects in the omega-3 group had significantly lower HAM-D scores at weeks 6 (p = .001) and 8 (p = .019), a significantly higher response rate (62% vs. 27%, p = .03), and a higher remission rate, although the latter did not reach statistical significance (38% vs. 18%" - See Mega Twin EPA at iHerb and Jarrow Max DHA at Amazon.com.

Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events - N Engl J Med. 2008 Mar 31 - "Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit" - Yeah but if you have to go with two drugs it sure seems like it's the least of all the evils regarding side effects.  See telmisartan at OffshoreRx1.com.

The glycemic index and cardiovascular disease risk - Curr Atheroscler Rep. 2007 Dec;9(6):479-85 - "dietary GI and/or glycemic load independently predict cardiovascular disease, with relative risk ratios of 1.2 to 1.7 comparing highest and lowest quintiles. In randomized controlled trials in overweight subjects, diets based on low-GI carbohydrates have produced better cardiovascular-related outcomes than conventional low-fat diets. Taken together, the findings suggest that health professionals may be able to improve cardiovascular outcomes by recommending the judicious use of low- GI/glycemic load foods"

New evidence for the cardiovascular benefits of long chain omega-3 Fatty acids - Curr Atheroscler Rep. 2007 Dec;9(6):434-40 - "The role of long chain omega-3 fatty acids (LC n-3 FAs) as cardioprotective agents has become even clearer with the recent publication of the Japan EPA Lipid Intervention Study. This was the largest randomized controlled trial in the field, and it demonstrated that even in a population with one of the highest LC n-3 FA intakes in the world, the addition of eicosapentaenoic acid could reduce cardiac events" - See Mega Twin EPA at iHerb.

Dehydroascorbic acid as an anti-cancer agent - Cancer Lett. 2008 Mar 28 - "dehydroascorbic acid has the remarkable ability to eliminate the aggressive mouse tumours, L1210, P388, Krebs sarcoma, and Ehrlich carcinoma"

• Dehydroascorbic acid - Wikipedia - "Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid"

CXCR4 and CXCL12 down-regulation: A novel mechanism for the chemoprotection of 3,3'-diindolylmethane for breast and ovarian cancers - Cancer Lett. 2008 Mar 28 - "Our data suggest that one mechanism whereby DIM protects against breast, ovarian, and possibly other cancers is through the repression of CXCR4 and/or CXCL12, thereby lowering the invasive and metastatic potential of these cells" - See diindolylmethane at Amazon.com.

Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study - Br J Nutr. 2008 Apr 1;:1-6 - "men in the highest quartile of flavonol and flavan-3-ol intakes had a relative risk of 0.55 (95 % CI 0.31, 0.99) and 0.59 (95 % CI 0.30, 1.14) for ischaemic stroke, respectively, as compared with the lowest quartile. After multivariate adjustment, the relative risk for CVD death in the highest quartile of flavanone and flavone intakes were 0.54 (95 % CI 0.32, 0.92) and 0.65 (95 % CI 0.40, 1.05), respectively"

Supplement Focus (Di-indolylmethane):

Related DIM Topics:

• Indole-3-carbinol (I3C) / Cruciferous Vegetables

DIM News & Research:

• See diindolylmethane at Amazon.com.
• Compound In Broccoli Could Boost Immune System, Says Study - Science Daily, 8/20/07 - "This study shows that there is a whole new universe of cancer regulation related to DIM ... There are virtually no other agents known that can both directly shut down the growth of cancer cells and enhance the function of the immune system at the same time"
• Broccoli, soy anti-cancer benefits suggested - Nutra USA, 4/16/07 - "this attraction between CXCR4 and CXCL12 draws cancer cells to the organs they spread to ... exposure with either DIM or genistein cut movement by 80 per cent"
• I3C & DIM - Natural, Dual-Action Protection Against Deadly Cancers - Life Extension Magazine, 1/06 - "Mounting preclinical and clinical evidence indicate[s] that indole-3-carbinol (I3C), a key bio-active food component in cruciferous vegetables, has multiple anticarcinogenic and antitumorigenic properties" - See indole-3-carbinol at Amazon.com.
• I have read that Indole-3-Carbinol (I3C) actually increases the activity of aromatase enzyme and that DIM does not - Life Extension Magazine, 3/01 - "In one study, men received I3C for one week; a profile of 13 estrogens was measured. The results were that I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol and 16 alpha-hydroxyestrone, were lower after I3C treatment [J Natl Cancer Inst 1997 May 21;89(10):718-23]. On the other hand, studies have shown that DIM can actually induce aromatase activity with a two-fold increase [Toxicol Sci 2001 May;61(1):40-8]" - The following are the two references for that statement:
• 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Diindolylmethanes Differentially Induce Cytochrome P450 1A1, 1B1, and 19 in H295R Human Adrenocortical Carcinoma Cells - Toxicol Sci 2001 May;61(1):40-8 - "DIM, but not TCDD, induced aromatase activity with an apparently maximal 2-fold increase at 10 µM; higher concentrations of DIM and many of its analogs were cytotoxic"
• Changes in levels of urinary estrogen metabolites after oral indole-3- carbinol treatment in humans - J Natl Cancer Inst 1997 May 21;89(10):718-23 - "In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16alpha- hydroxyestrone, were lower after I3C treatment" - So if C-2 estrogens are increased, is that bad in men?  I don't know. The following are all I could find:
  • Estrogen Metabolism - immunacare.com - "C-2 metabolites are essentially devoid of peripheral biological activity, as shown in studies on uterine weight, gonadotrophin secretion, and cell proliferation {1}. 2-Hydroxyestrogen has even been found to exert a modest anti-estrogenic effect {2,3}, and has been called "the good estrogen" {4}. The 16a-hydroxylated metabolites, 16a-hydroxyestrone (16OHE1) and estriol (E3), are estrogen agonists {5}."
  • Effects of Pesticides on the Ratio of 16/2-Hydroxyestrone: A Biologic Marker of Breast Cancer Risk - Environmental Health Perspectives 103, Supplement 7, October 1995 -"Estradiol metabolism proceeds by hydroxylation at one of two mutually exclusive sites at C-2 and C-16. The catechol pathway yields the weakly estrogenic 2-hydroxyestrone (2-OHE1), which inhibits breast cell proliferation" - If that means, and I think it does, that the C-2 metabolites inhibit breast cell growth, that would definitely be a good thing for men.
• I3C vs DIM - Life Extension Foundation, 1/02
• Natural estrogen replacement article by Jonathan Wright MD. - IAS - "DIM may reduce prostate cancer incidence as it has been shown to stop human cancer cells from growing by (54-61%) and provoking the cells to self-destruct (apoptosis). DIM also improves prostate function, enhances insulin sensitivity and increases abdominal fat loss."
• I3C and DIM: Keys to Cancer Prevention? - Nutrition Science News, 4/01 - "Increased 16-alpha-hydroxyestrone production has been linked to an increase in breast cancer. Based on estrogen metabolism's influence on breast-cancer risk, researchers speculate that reducing hydroxylation of estrone's 16th carbon and increasing hydroxylation of the second carbon would be a wise, protective measure ... The minimum effective dose to increase the ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone was 300 mg/day ... Most of the research thus far has focused on I3C, a phytonutrient converted by stomach acid to DIM, indolylcarbazole, and other metabolites ... A 350­500 mg dose of I3C is roughly equal to 300­500 mg of raw cabbage or brussels sprouts or about 3 cups of broccoli"
• I've heard quite a bit about a broccoli extract called indole-3-carbinol (I3C). What is the difference between it and the other broccoli extract called diindolylmethane (DIM)? - Nutrition Science News, 2/01 - "Certainly DIM by itself has an effect, but these other products may also be important for the overall cancer-inhibiting action. As most of the research to date has focused on I3C, it seems prudent at this time to use supplements containing I3C instead of DIM"
• The Cruciferous Choice: DIM or I3C? - Michael A. Zeligs, M.D. - "It is well documented that estrogen accumulates in the prostate gland starting at age 50 (42) and that estrogen is associated with the degree of prostate enlargement ... Using DIM in men avoids accelerating testosterone metabolism, especially regarding unwanted conversion of testosterone into estrogen. In the safety study reported (11), I3C and not DIM increased activity of "aromatase" (CYP19), the enzyme responsible for converting testosterone into estrogen"
• DIM FAQ - "DIM helps to eliminate active estrogen from the male body by promoting its conversion into the "good" metabolites. These metabolites then free up testosterone by bumping it off the testosterone-binding proteins. The end result is a healthier balance of testosterone to estrogen and more free testosterone circulating in the body. In scientific studies, high levels of testosterone and low levels of estrogen have been linked to lean body mass, an efficient fat-burning metabolism, and low abdominal obesity. Other benefits from testosterone are improved mood, more interest in sex, and better physical conditioning. In this chapter, we'll explore these issues in more detail."
• Di-indolylmethane - Jonathan Wright MD's, International Anti-aging Systems
• Reducing the Hormone Related Cancer Risk (Or cabbages, sex hormones and their metabolites) - Jonathan Wright M.D., International Anti-aging Systems - "Among other things, estradiol is metabolized into estrone, which in turn can be metabolized into either 2-hydroxyestrone or 16 alpha-hydroxyestrone. Importantly, there's an “inverse” relationship here: if more 2-hydroxyestrone is made, less 16 alpha-hydroxyestrone is usually made, and vice-versa. In at least one of his publications, Dr. Bradlow has termed 2-hydroxyestrone “good estrogen”, and has given us evidence that 16 alpha hydroxyestrone is “bad estrogen”. He writes: “Evidence from a long series of studies has demonstrated a specific role for 16a-hydroxyestrone as a transforming estrogen, which is more potent than estradiol itself.” (“Transforming” refers to the tendency of 16a-hydroxyestrone to increase cellular growth and proliferation, and even cancerous transformation in estrogen-responsive tissues). He goes on to note that the preponderance of evidence shows that, by contrast, 2-hydroxyestrone is non-carcinogenic or even anti-carcinogenic. He also notes that treatment which reduces the 2/16a hydroxyestrone ratio has been shown to reverse the growth of human larygneal papillomas, caused by the same family of viruses (HPV) implicated in cervical cancers.  Other researchers hypothesize that cancer in other tissues, including uterus, prostate, liver and kidney, may be affected by the 2/16a hydroxyestrone ratio as well as other estrogen metabolites"
• Estrogen Levels Linked To Head And Neck Cancers - Doctor's Guide, 9/28/99 - "Similar effects (to alter estrogen metabolic pathways) could be exerted by vegetables including broccoli and cauliflower, which contain the phytochemical compound indole-3-carbinol."
• I3C/DIM - Recurrent Respiratory Papillomatosis Foundation

DIM Abstracts:

• CXCR4 and CXCL12 down-regulation: A novel mechanism for the chemoprotection of 3,3'-diindolylmethane for breast and ovarian cancers - Cancer Lett. 2008 Mar 28 - "Our data suggest that one mechanism whereby DIM protects against breast, ovarian, and possibly other cancers is through the repression of CXCR4 and/or CXCL12, thereby lowering the invasive and metastatic potential of these cells"
• Indole-3-carbinol as a chemopreventive and anti-cancer agent - Cancer Lett. 2008 Feb 29 - "Indole-3-carbinol and its metabolite 3,3'-diindoylmethane (DIM) target multiple aspects of cancer cell-cycle regulation and survival including Akt-NFkappaB signaling, caspase activation, cyclin-dependent kinase activities, estrogen metabolism, estrogen receptor signaling, endoplasmic reticulum stress, and BRCA gene expression. This broad spectrum of anti-tumor activities in conjunction with low toxicity underscores the translational value of indole-3-carbinol and its metabolites in cancer prevention/therapy. Furthermore, novel anti-tumor agents with overlapping underlying mechanisms have emerged via structural optimization of indole-3-carbinol and DIM, which may provide considerable therapeutic advantages over the parental compounds with respect to chemical stability and anti-tumor potency. Together, these agents might foster new strategies for cancer prevention and therapy"