Joel Evans, MD reviews several current research papers in his January Literature Review.

by Joel M. Evans, MD

Antioxid Redox Signal. 2009 Jan;11(1):47-58.  Oral administration of blueberry inhibits angiogenic tumor growth and enhances survival of mice with endothelial cell neoplasm. Gordillo G, Fang H, Khanna S, Harper J, Phillips G, Sen CK. Division of Plastic Surgery, Department of Surgery, Davis Heart Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, USA.|

Endothelial cell neoplasms are the most common soft tissue tumor in infants. Subcutaneous injection of spontaneously transformed murine endothelial (EOMA) cells results in development of hemangioendothelioma (HE). We have previously shown that blueberry extract (BBE) treatment of EOMA cells in vitro prior to injection in vivo can significantly inhibit the incidence and size of developing HE. In this study, we sought to determine whether oral BBE could be effective in managing HE and to investigate the mechanisms through which BBE exerts its effects on endothelial cells. A dose-dependent decrease in HE tumor size was observed in mice receiving daily oral gavage feeds of BBE. Kaplan-Meier survival curve showed significantly enhanced survival for mice with HE tumors given BBE, compared to control. BBE treatment of EOMA cells inhibited both c-Jun N-terminal kinase (JNK) and NF-kappaB signaling pathways that culminate in monocyte chemoattractant protein-1 (MCP-1) expression required for HE development. Antiangiogenic effects of BBE on EOMA cells included decreased proliferation by BrdU assay, decreased sprouting on Matrigel, and decreased transwell migration. Thus, this work provides first evidence demonstrating that BBE can limit tumor formation through antiangiogenic effects and inhibition of JNK and NF-kappaB signaling pathways. Oral administration of BBE represents a potential therapeutic antiangiogenic strategy for treating endothelial cell neoplasms in children.

This article shows, once again, how healthy foods like blueberries, impart their health promoting effects by many different mechanisms. Blueberries have traditionally been thought of as antioxidants, but here Gordillo et al. demonstrate an antiangiogenic effect of actually decreasing different parameters of tumor growth with blueberry extract.

Though this study focused on an animal model of a pediatric tumor, there is no reason not to believe that there will be similar affects in a whole range of tumors. In fact, research has already been published on the anti-cancer effects of blueberry extract on breast, colon and cervical cancer cells. (Berry extracts exert different antiproliferative effects against cervical and colon cancer cells grown in vitro. McDougall GJ, Ross HA, Ikeji M, Stewart D.J Agric Food Chem. 2008 May 14;56(9):3016-23., Anticarcinogenic Activity of Strawberry, Blueberry, and Raspberry Extracts to Breast and Cervical Cancer Cells. Wedge DE, Meepagala KM, Magee JB, Smith SH, Huang G, Larcom LL. J Med Food. 2001 Spring;4(1):49-51.) In light of the scientific plausibility of effectiveness and the lack of toxicity of blueberry extract it makes sense to strongly consider adding blueberries or extract to the diet of cancer patients.
Cancer. 2009 Jan 6. [Epub ahead of print]  Body mass index and risk of ovarian cancer.
Leitzmann MF, Koebnick C, Danforth KN, Brinton LA, Moore SC, Hollenbeck AR, Schatzkin A, Lacey JV Jr.Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.

BACKGROUND:: Convincing epidemiologic evidence links excess body mass to increased risks of endometrial and postmenopausal breast cancers, but the relation between body mass index (BMI) and ovarian cancer risk remains inconclusive. Potential similarities regarding a hormonal mechanism in the etiology of female cancers highlight the importance of investigating associations according to menopausal hormone therapy (MHT) use. However, to the authors’ knowledge, data addressing whether the relation between BMI and ovarian cancer differs by MHT use are very sparse. METHODS:: The authors prospectively investigated the association between BMI and ovarian cancer among 94,525 US women who were followed between 1996 through 1997 to December 31, 2003. During 7 years of follow-up, 303 epithelial ovarian cancer cases were documented. RESULTS:: Compared with normal weight women (BMI of 18.5-24.9 kg/m(2)), the multivariate relative risk (MVRR) of ovarian cancer for obese women (BMI of >/=30 kg/m(2)) in the cohort as a whole was 1.26 (95% confidence interval [95% CI], 0.94-1.68). Among women who never used MHT, the MVRR for obese versus normal weight women was 1.83 (95% CI, 1.18-2.84). In contrast, no relation between BMI and ovarian cancer was apparent among women who ever used MHT (MVRR = 0.96; 95% CI, 0.65-1.43; P interaction = 0.02). Exploratory analyses also suggested a positive association between BMI and ovarian cancer among women without a family history of ovarian cancer (MVRR comparing obese vs normal weight women = 1.36; 95% CI, 1.00-1.86), but no relation with BMI was apparent among women with a positive family history of ovarian cancer (MVRR = 0.74; 95% CI, 0.34-1.62 [P interaction = .02]). CONCLUSIONS:: Based on the results of the current study, the authors suspect that obesity is associated with enhanced ovarian cancer risk through a hormonal mechanism.


There is a rapidly growing literature on the relationship between obesity and many different cancers. Multiple mechanisms have been proposed, the majority focusing on the endocrine and inflammatory effects of visceral adipose tissue. It has even been suggested that environmental toxins promote cancer not only by a direct effect but also by being a direct cause of obesity (Overweight/obesity and cancer genesis: More than a biological link. Irigaray et al., Biomedicine & Pharmacotherapy 61 (2007) 665-678).

This article clearly shows that obesity is a risk factor for ovarian cancer, which is important because ovarian cancer is so difficult to detect in its early stages. At long last, clinicians now have a proven strategy (obtaining ideal body weight) that can impact the incidence of this devastating disease.

 1: Aliment Pharmacol Ther. 2009 Jan 20. [Epub ahead of print]  Clinical trial: B Vitamins improve health in coeliac patients living on a gluten-free diet. Hallert C, Svensson M, Tholstrup J, Hultberg B.Coeliac Centre, Norrköping Hospital, Norrköping, Sweden.

Summary Background. Coeliac patients living on a gluten-free diet show vitamin deficiency and reduced subjective health status. Aim. To study the biochemical and clinical effects of B vitamin supplementation in adults with longstanding coeliac disease. Methods. In a double blind placebo controlled multicentre trial, 65 coeliac patients (61% women) aged 45-64 years on a strict gluten-free diet for several years were randomized to a daily dose of 0.8 mg folic acid,0.5 mg cyanocobalamin and 3 mg pyridoxine or placebo for 6 months. The outcome measures were psychological general well-being and the plasma total homocysteine (tHcy) level, marker of B vitamin status. Results. Fifty-seven patients (88%) completed the trial. The tHcy level was baseline median 11.7 mumol/L (7.4 -23.0), significantly higher than in matched population controls (10.2 mumol/L (6.7-22.6) (P<0.01). Following vitamin supplementation, tHcy dropped a median of 34% (P<0.001), accompanied by significant improvement in well-being (P<0.01), notably Anxiety (P<0.05) and Depressed Mood (P<0.05) for patients with poor well-being. Conclusions. Adults with longstanding coeliac disease taking extra B vitamins for 6 months showed normalized tHcy and significant improvement in general well-being, suggesting that B vitamins should be considered in people advised to follow a gluten-free diet.


With the increasing awareness of celiac disease and gluten sensitivity, more patients than ever are being placed on gluten free diets, often with dramatic improvement in their symptoms, whether they be extra intestinal or gut related. This article tells us that symptoms can be further improved by supplementing these patients with a B Complex Vitamin in addition to their gluten free diet. In addition, homocysteine levels, which were found to be elevated in the celiac group, were reduced by the B vitamins. Though this is not unexpected, it gives further weight to the recommendation that patients with celiac disease or gluten sensitivity be give a B Complex Vitamin daily.

Int J Gynaecol Obstet. 2009 Jan 18. [Epub ahead of print]  Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. Teran E, Hernandez I, Nieto B, Tavara R, Ocampo JE, Calle A. Experimental Pharmacology and Cellular Metabolism Unit, Biomedical Center, Central University of Ecuador, Quito, Ecuador.

OBJECTIVE: To assess whether supplementation with Coenzyme Q10 (CoQ10) during pregnancy reduces the risk of pre-eclampsia. METHODS: Women at increased risk of pre-eclampsia were enrolled in a randomized, double-blind, placebo-controlled trial. Women were assigned to receive 200 mg of CoQ10 or placebo daily from 20 weeks of pregnancy until delivery. The primary outcome was rate of pre-eclampsia. Statistical analyses were by intention-to-treat. RESULTS: Of the 235 women enrolled in the trial, 118 were randomized to receive CoQ10 and 117 received a placebo. A total of 197 (83.8%) women were followed-up. The overall rate of pre-eclampsia was 20% (n=47). Thirty women (25.6%) in the placebo group developed pre-eclampsia compared with 17 women (14.4%) in the CoQ10 group, and this reduction was significant (P=0.035) (relative risk [RR] 0.56; 95% confidence interval [CI], 0.33-0.96). CONCLUSION: Supplementation with CoQ10 reduces the risk of developing pre-eclampsia in women at risk for the condition.


The search for the cause (s) of preeclampsia (elevated blood pressure, proteinuria, and headache in pregnancy) has been the focus of many investigators for a long time. There have been many theories, but a consistent one involves free radical damage to the placental microvasculature causing an initiation of biochemical and pathologic events leading to the full blown clinical syndrome. However, recent multicenter prospective trials of different combinations of antioxidants have failed to show an real benefit in reducing the risk of preeclampsia (Poston et al., Lancet. 2006 Apr 8;367(9517):1145-54 and Rumbold et al, NEJM, 2006 Apr 27;354(17):1796-806). This is surprisingly true even in the context of the extremely powerful biologic plausibility seen in laboratory studies (Kim et al. J Obstet Gynaecol Res. 2006 Feb;32(1):32-41 Total peroxyl radical-trapping ability and anti-oxidant vitamins of the umbilical venous plasma and the placenta in pre-eclampsia).

It is this historical context of strong biologic plausibility and negative prospective randomized studies that gives this study its power. Finally we have identified the proper type of antioxidant intervention to decrease the incidence of this prevalent pregnancy complication that, when severe, has killed mothers and babies. 

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