Dr. Ron’s Research Review – June 10, 2010

This week’s research focuses on metabolic syndrome and insulin resistance:

The effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women

Metabolic syndrome after menopause and the role of hormones

Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins

Yacon syrup: beneficial effects on obesity and insulin resistance in humans

In the news: Tocotrienols

Can supplement limit stroke damage? By Jane Glenn Haas, Seattle Times, June 7, 2010 Link

In the news: Eribulin and Halichondrin B

Experimental drug prolongs survival in treatment-resistant breast cancer, study finds, By Thomas H. Maugh, Seattle Times, June 7, 2010 Link

Eribulin (INN, codenamed E7389) is an investigational anticancer drug. Structurally, eribulin is a fully synthetic macrocyclic ketone analogue of the marine sponge natural product halichondrin B, a potent mitotic inhibitor with a unique mechanism of action found in the Halichondria genus of sponges. Link Link2

Dr. Ron

Yacon syrup

From Wikipedia, the free encyclopedia

The tuberous roots of the yacón plant (Smallanthus sonchifolius)Yacón syrup is a sweetening agent extracted from the tuberous roots of the yacón plant (Smallanthus sonchifolius) indigenous to the Andes mountains.[1]It was used by the Incas. In Peru people eat yacon because of its nutritional properties—few calories and low sugar levels. In Bolivia yacón roots are eaten by people with diabetes or other digestive and renal disorders. Where as In Brazil the dried leaves are used to make yacón tea, said to be antidiabetic.[2]The syrup contains up to 50% of FOS (fructooligosacharides). The consumption of FOS does not increase blood glucose. However, since any inulin-derived sweetener has large amounts of fructose, the same concerns about the health effects of fructose apply.It is usually made with an evaporator, like the ones used to make maple syrup.[1]. It has a taste similar to molasses or caramelized sugar.[3] In a study by Yoshida et al. (2002), an enzyme solution of yacon was determined to be a better antioxidant than enzyme solutions of potato, mushroom, eggplant and edible burdock.[4]

Abstracts

Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women

            (Salpeter, Walsh et al. 2006) Download

AIM: To quantify the effects of hormone-replacement therapy (HRT) on components of the metabolic syndrome in postmenopausal women. METHODS: Comprehensive searches of electronic databases were performed from April 1966 to October 2004. We included randomized controlled trials that were of at least 8 weeks duration and evaluated the effect of HRT on metabolic, inflammatory or thrombotic components. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Subgroup analysis evaluated the effects for transdermal and oral treatment and for diabetic and non-diabetic women. RESULTS: Pooled results of 107 trials showed that HRT reduced abdominal fat [-6.8% (CI, -11.8 to -1.9%)], HOMA-IR [-12.9% (CI, -17.1 to -8.6%)] and new-onset diabetes [relative risk 0.7 (CI, 0.6-0.9)] in women without diabetes. In women with diabetes, HRT reduced fasting glucose [-11.5% (CI, -18.0 to -5.1%)] and HOMA-IR [-35.8% (CI, -51.7 to -19.8%)]. HRT also reduced low-density lipoprotein/high-density lipoprotein cholesterol ratio [-15.7% (CI, -18.0 to -13.5%)], lipoprotein(a) [Lp(a)] [-25.0% [CI, -32.9 to -17.1%)], mean blood pressure [-1.7% (CI, -2.9 to -0.5%)], E-selectin [-17.3% (CI, -22.4 to -12.1%)], fibrinogen [-5.5% (CI, -7.8 to -3.2%)] and plasminogen activator inhibitor-1 [-25.1% (CI, -33.6 to -15.5%)]. Oral agents produced larger beneficial effects than transdermal agents, but increased C-reactive protein (CRP) [37.6% (CI, 17.4-61.3%)] and decreased protein S [-8.6% CI, -13.1 to -4.1%)], while transdermal agents had no effect. CONCLUSIONS: HRT reduces abdominal obesity, insulin resistance, new-onset diabetes, lipids, blood pressure, adhesion molecules and procoagulant factors in women without diabetes and reduced insulin resistance and fasting glucose in women with diabetes. Oral agents adversely affected CRP and protein S, while transdermal agents had no effects.

Metabolic syndrome after menopause and the role of hormones

(Lobo 2008) Download

OBJECTIVES: The purpose of this review is to focus on the importance of metabolic syndrome (MBS) and its increased prevalence in postmenopausal (PM) women. Also the role of hormonal therapy in PM women with MBS will be discussed. METHODS: Review of the relevant literature and results from recent clinical trials. RESULTS: MBS may occur in 40% of PM women and is largely determined by overweight status and obesity. Weight gain, particularly an increase in central fat mass increases in PM women, beginning a few years prior to menopause. Hormonal Therapy (HT) in normal PM women, generally decreases abdominal fat, but the effect of transdermal estrogen is preferable to oral therapy in this regard. In women with MBS, oral therapy was found to increase leptin and the leptin/adiponectin ratio, while transdermal therapy showed no changes. HT has been found to improve insulin resistance in PM women, although the data are mixed. In women with MBS, oral therapy was found to worsen parameters of insulin resistance, while transdermal therapy had minimal effects overall. Women with MBS have elevations in several inflammation and coagulation factors. Both oral and transdermal HT reduce inflammation markers except for levels of CRP and MMP-9, which increase with oral therapy, but are unaffected by the transdermal route. Oral estrogen has a small pro-coagulant effect, not observed with transdermal therapy, in both normal PM women and those with MBS. The beneficial effects of HT on lipids occur in PM women with and without MBS, although the changes in the latter are minimal. Blood pressure was not affected by HT in women with MBS. CONCLUSIONS: Weight gain and obesity largely drives the increased prevalence of MBS in PM women. Use of HT is beneficial overall for reducing many of the parameters of MBS. Our own data would suggest that in MBS, transdermal therapy may be preferable to oral therapy, at least in standard doses.

Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins

            (Gonzalez-Periz, Horrillo et al. 2009) Download

Omega-3-polyunsaturated fatty acids (omega-3-PUFAs) have well-documented protective effects that are attributed not only to eicosanoid inhibition but also to the formation of novel biologically active lipid mediators (i.e., resolvins and protectins). In this study, we examined their effects on ob/ob mice, an obesity model of insulin resistance and fatty liver disease. Dietary intake of omega-3-PUFAs had insulin-sensitizing actions in adipose tissue and liver and improved insulin tolerance in obese mice. Genes involved in insulin sensitivity (PPARgamma), glucose transport (GLUT-2/GLUT-4), and insulin receptor signaling (IRS-1/IRS-2) were up-regulated by omega-3-PUFAs. Moreover, omega-3-PUFAs increased adiponectin, an anti-inflammatory and insulin-sensitizing adipokine, and induced AMPK phosphorylation, a fuel-sensing enzyme and a gatekeeper of the energy balance. Concomitantly, hepatic steatosis was alleviated by omega-3-PUFAs. A lipidomic analysis with liquid chromatography/mass spectrometry/mass spectrometry revealed that omega-3-PUFAs inhibited the formation of omega-6-PUFA-derived eicosanoids, while triggering the formation of omega-3-PUFA-derived resolvins and protectins. Moreover, representative members of these lipid mediators, namely resolvin E1 and protectin D1, mimicked the insulin-sensitizing and antisteatotic effects of omega-3-PUFAs and induced adiponectin expression to a similar extent that of rosiglitazone, a member of the thiazolidinedione family of antidiabetic drugs. Taken together, these findings uncover beneficial actions of omega-3-PUFAs and their bioactive lipid autacoids in preventing obesity-induced insulin resistance and hepatic steatosis.

Yacon syrup: beneficial effects on obesity and insulin resistance in humans

            (Genta, Cabrera et al. 2009) Download

BACKGROUND & AIMS: Syrup obtained from yacon roots could be well positioned as a nutraceutical product due to its high fructooligosaccharides content. We examined the beneficial effects and tolerance of yacon syrup on human health. METHODS: Obese and slightly dyslipidemic pre-menopausal women were studied over a 120-day period in a double-blind placebo-controlled experiment. We used two doses of yacon syrup, 0.29 g and 0.14 g fructooligosaccharides/kg/day. At the start and end of the study, anthropometric measurements, blood glucose, calcium, lipid and insulin concentrations and Homeostasis Model Assessment index were determined. RESULTS: The recommended daily consumption of yacon syrup with no undesirable gastrointestinal effects is 0.14 g fructooligosaccharides/kg. Daily intake of yacon syrup produced a significant decrease in body weight, waist circumference and body mass index. Additionally, decrease in fasting serum insulin and Homeostasis Model Assessment index was observed. The consumption of yacon syrup increased defecation frequency and satiety sensation. Fasting glucose and serum lipids were not affected by syrup treatment and the only positive effect was found in serum LDL-cholesterol levels. CONCLUSIONS: Yacon syrup is a good source of fructooligosaccharides and its long-term consumption produced beneficial health effects on obese pre-menopausal women with insulin resistance.

References

Genta, S., W. Cabrera, et al. (2009). "Yacon syrup: beneficial effects on obesity and insulin resistance in humans." Clin Nutr 28(2): 182-7.

Gonzalez-Periz, A., R. Horrillo, et al. (2009). "Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins." FASEB J 23(6): 1946-57.

Lobo, R. A. (2008). "Metabolic syndrome after menopause and the role of hormones." Maturitas 60(1): 10-8.

Salpeter, S. R., J. M. Walsh, et al. (2006). "Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women." Diabetes Obes Metab 8(5): 538-54.