STENDEC

An American biotech company has launched clinical trials in Colombia to test a new therapy designed to reverse the aging process, and in turn, treat age-related diseases, according to news reports. But to steal a sip from this purported fountain of youth, participants in the trial must first fork over $1 million — a fee that seems even more astronomical when you consider that most clinical trials are either free or provide participants with financial compensation, according to a report by OneZero, a Medium publication about tech and science. The pricey trial is being run by Libella Gene Therapeutics, a Kansas-based company whose website proclaims that "the future is here." The company announced its intention to test its anti-aging remedies in Cartagena, Colombia, in 2018, and began recruiting for the trials in October of this year. Using a single-gene therapy, Libella aims to "prevent, delay, or even reverse" the general effects of aging, as well as treat diseases that emerge in old age, such as Alzheimer's, according to ClinicalTrials.gov. Full Live Science Article

The so-called Blue Zones are regions where there’s a high proportion of very old people, nonagenarians and centenarians. Is that really the truth about the Blue Zones? What's The Truth About Blue Zones The observation of individuals attaining remarkable ages, and their concentration into geographic sub-regions or ‘blue zones’, has generated considerable scientific interest. Proposed drivers of remarkable longevity include high vegetable intake, strong social connections, and genetic markers. Here, we reveal new predictors of remarkable longevity and ‘supercentenarian’ status. In the United States, supercentenarian status is predicted by the absence of vital registration. The state-specific introduction of birth certificates is associated with a 69-82% fall in the number of supercentenarian records. In Italy, which has more uniform vital registration, remarkable longevity is instead predicted by low per capita incomes and a short life expectancy. Finally, the designated ‘blue zones’ of Sardinia, Okinawa, and Ikaria corresponded to regions with low incomes, low literacy, high crime rate and short life expectancy relative to their national average. As such, relative poverty and short lifespan constitute unexpected predictors of centenarian and supercentenarian status, and support a primary role of fraud and error in generating remarkable human age records. Supercentenarians and the oldest-old are concentrated into regions with no birth certificates and short lifespans

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Related drug, liraglutide is indicated for obesity, specifically coincident with HTN.

Fat loss?

J Manag Care Spec Pharm. 2018 Sep;24(9-a Suppl):S14-S29. doi: 10.18553/jmcp.2018.24.9-a.s14. Glycemic Efficacy, Weight Effects, and Safety of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists. Handelsman Y1, Wyne K2, Cannon A3, Shannon M4, Schneider D5. Abstract This article provides an overview of the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic GLP-1 receptors, which increases insulin secretion, delays gastric emptying, and increases satiety. As a class, GLP-1 RAs lower A1c levels and have been associated with reductions in weight and blood pressure and reduced fluctuations in glucose levels, and they have a low risk of hypoglycemia. Exenatide extended release (ER) and dulaglutide monotherapy have shown similar or superior reductions in A1c and weight compared with various oral antidiabetic drugs (OADs). Semaglutide has been shown to reduce both A1c and body weight compared with placebo and, in head-to-head studies versus both exenatide ER and dulaglutide, showed greater reductions in A1c and body weight. Once-weekly GLP-1 RAs have also been evaluated as add-on therapy in the continuum of care for the treatment of T2DM in combination with a variety of background medications, including 1 or more OADs (metformin, sulfonylureas, and/or thiazolidinediones), basal insulin, and prandial insulin. Gastrointestinal adverse events (e.g., nausea, vomiting, and diarrhea) are the most common side effects with once-weekly GLP-1 RAs. Rates of hypoglycemia, and especially major/severe hypoglycemia, are low with once-weekly GLP-1 RAs but, as expected, are higher when used in combination with sulfonylureas or insulin. These once-weekly GLP-1 RAs provide a safe and effective treatment option for patients with T2DM and may offer improved convenience and possibly greater adherence compared with daily GLP-1 RAs. PMID: 30156445 FFT

Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. O'Neil PM1, Birkenfeld AL2, McGowan B3, Mosenzon O4, Pedersen SD5, Wharton S6, Carson CG7, Jepsen CH7, Kabisch M7, Wilding JPH8. Obesity and Endocrinology Research, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. Electronic address: j.p.h.wilding@liverpool.ac.uk. Abstract BACKGROUND: Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss. METHODS: We did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m2 or more. We randomly assigned participants (6:1) to each active treatment group (ie, semaglutide [0·05 mg, 0·1 mg, 0·2 mg, 0·3 mg, or 0·4 mg; initiated at 0·05 mg per day and incrementally escalated every 4 weeks] or liraglutide [3·0 mg; initiated at 0·6 mg per day and escalated by 0·6 mg per week]) or matching placebo group (equal injection volume and escalation schedule to active treatment group) using a block size of 56. All treatment doses were delivered once-daily via subcutaneous injections. Participants and investigators were masked to the assigned study treatment but not the target dose. The primary endpoint was percentage weight loss at week 52. The primary analysis was done using intention-to-treat ANCOVA estimation with missing data derived from the placebo pool. This study is registered with ClinicalTrials.gov, number NCT02453711. FINDINGS: Between Oct 1, 2015, and Feb 11, 2016, 957 individuals were randomly assigned (102-103 participants per active treatment group and 136 in the pooled placebo group). Mean baseline characteristics included age 47 years, bodyweight 111·5 kg, and BMI 39·3 kg/m2. Bodyweight data were available for 891 (93%) of 957 participants at week 52. Estimated mean weight loss was -2·3% for the placebo group versus -6·0% (0·05 mg), -8·6% (0·1 mg), -11·6% (0·2 mg), -11·2% (0·3 mg), and -13·8% (0·4 mg) for the semaglutide groups. All semaglutide groups versus placebo were significant (unadjusted p≤0·0010), and remained significant after adjustment for multiple testing (p≤0·0055). Mean bodyweight reductions for 0·2 mg or more of semaglutide versus liraglutide were all significant (-13·8% to -11·2% vs -7·8%). Estimated weight loss of 10% or more occurred in 10% of participants receiving placebo compared with 37-65% receiving 0·1 mg or more of semaglutide (p<0·0001 vs placebo). All semaglutide doses were generally well tolerated, with no new safety concerns. The most common adverse events were dose-related gastrointestinal symptoms, primarily nausea, as seen previously with GLP-1 receptor agonists. INTERPRETATION: In combination with dietary and physical activity counselling, semaglutide was well tolerated over 52 weeks and showed clinically relevant weight loss compared with placebo at all doses. PMID: 30122305 Weight loss of +10% in a year is hella impressive. This stuff is also now available as an oral formulation.

Running research: Heel-toe or toe-heel? December 12, 2019 Science News New research from La Trobe University suggests there is no evidence that changing a runner's strike pattern will help prevent injuries or give them a speed boost. In a bid to avoid shin splints, sore knees and other injuries, many runners have adopted a toe-to-heel trend, running on the balls of their feet. This is often encouraged by coaches and health professionals. However, in research out this week in Sports Medicine, La Trobe injury researcher and physiotherapist Dr Christian Barton found there is no evidence to suggest running on the front of your feet reduces injury risk or improves performance. "We analysed 53 studies which looked at the impact of forefoot, rearfoot and flatfoot running patterns on injury, running economy and running biomechanics," senior author of the study, Dr Barton said "Our comprehensive review suggests that telling someone to run on the ball of their foot instead of their heel may make them less efficient, at least in the short term. Additionally, there is no evidence either way on whether running on the balls of your feet reduces injury." Dr Barton said switching your running style shifts the body's loads but doesn't make them disappear. "Running toe-heel might help injuries at the knee, where loads are reduced. However, it may cause injuries to the feet and ankle, where loads are increased," Dr Barton said. "Put simply, when it comes to running style: If it ain't broke, don't fix it." Journal Reference: Laura M. Anderson, Daniel R. Bonanno, Harvi F. Hart, Christian J. Barton. What are the Benefits and Risks Associated with Changing Foot Strike Pattern During Running? A Systematic Review and Meta-analysis of Injury, Running Economy, and Biomechanics. Sports Medicine, 2019

Front Endocrinol (Lausanne). 2018 Jul 25;9:427. doi: 10.3389/fendo.2018.00427. eCollection 2018. 3,5-Diiodothyronine: A Novel Thyroid Hormone Metabolite and Potent Modulator of Energy Metabolism. Senese R1, de Lange P1, Petito G1, Moreno M2, Goglia F2, Lanni A1. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "L. Vanvitelli" , Caserta, Italy. Department of Sciences and Technologies, University of Sannio, Benevento, Italy. Abstract Over 30 years of research has demonstrated that 3,5-diiodo-L-thyronine (3,5-T2), an endogenous metabolite of thyroid hormones, exhibits interesting metabolic activities. In rodent models, exogenously administered 3,5-T2 rapidly increases resting metabolic rate and elicits short-term beneficial hypolipidemic effects; however, very few studies have evaluated the effects of endogenous and exogenous T2 in humans. Further analyses on larger cohorts are needed to determine whether 3,5-T2 is a potent additional modulator of energy metabolism. In addition, while several lines of evidence suggest that 3,5-T2 mainly acts through Thyroid hormone receptors (THRs)- independent ways, with mitochondria as a likely cellular target, THRs-mediated actions have also been described. The detailed cellular and molecular mechanisms through which 3,5-T2 elicits a multiplicity of actions remains unknown. Here, we provide an overview of the most recent literature on 3,5-T2 bioactivity with a particular focus on short-term and long-term effects, describing data obtained through in vivo and in vitro approaches in both mammalian and non-mammalian species. PMID: 30090086 FFT

3,5-diiodo-L-thyronine increases resting metabolic rate and reduces body weight without undesirable side effects. Antonelli A1, Fallahi P, Ferrari SM, Di Domenicantonio A, Moreno M, Lanni A, Goglia F. Department of Internal Medicine, University of Pisa, Pisa, Italy. alessandro.antonelli@med.unipi.it Abstract Recently, it was demonstrated that 3,5-diiodo-L-thyronine (T2) stimulates the resting metabolic rate (RMR), and reduces body-weight gain of rats receiving a high-fat diet. The aim of this study is to examine the effects of chronic T2 administration on basal metabolic rate and body weight in humans. Two euthyroid subjects volunteered to undergo T2 administration. Body weight, body mass index, blood pressure, heart rate, electrocardiogram, thyroid and liver ultrasonography, glycemia, total cholesterol, triglycerides, free T3 (FT3), free T4 (FT4), T2, thyroid stimulating hormone (TSH) and RMR were evaluated at baseline and at the end of treatment. RMR increased significantly in each subject. After continuing the T2 treatment for a further 3 weeks (at 300 mcg/day), body weight was reduced significantly (p<0.05) (about 4 percent), while the serum levels of FT3, FT4 and TSH, were unchanged. No side effects were observed at the cardiac level in either subject. No significant change was observed in the same subjects taking placebo. PMID: 22217997 n=2 FASEB J. 2005 Sep;19(11):1552-4. Epub 2005 Jul 12. 3,5-diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats. Lanni A1, Moreno M, Lombardi A, de Lange P, Silvestri E, Ragni M, Farina P, Baccari GC, Fallahi P, Antonelli A, Goglia F. Dipartimento di Scienze della Vita, Seconda Università di Napoli, Caserta, Italy. antonia.lanni@unina2.it Abstract The effect of thyroid hormones on metabolism has long supported their potential as drugs to stimulate fat reduction, but the concomitant induction of a thyrotoxic state has greatly limited their use. Recent evidence suggests that 3,5-diiodo-L-thyronine (T2), a naturally occurring iodothyronine, stimulates metabolic rate via mechanisms involving the mitochondrial apparatus. We examined whether this effect would result in reduced energy storage. Here, we show that T2 administration to rats receiving a high-fat diet (HFD) reduces both adiposity and body weight gain without inducing thyrotoxicity. Rats receiving HFD + T2 showed (when compared with rats receiving HFD alone) a 13% lower body weight, a 42% higher liver fatty acid oxidation rate, appoximately 50% less fat mass, a complete disappearance of fat from the liver, and significant reductions in the serum triglyceride and cholesterol levels (-52% and -18%, respectively). Thyroid hormones and thyroid-stimulating hormone (TSH) serum levels were not influenced by T2 administration. The biochemical mechanism underlying the effects of T2 on liver metabolism involves the carnitine palmitoyl-transferase system and mitochondrial uncoupling. If the results hold true for humans, pharmacological administration of T2 might serve to counteract the problems associated with overweight, such as accumulation of lipids in liver and serum, without inducing thyrotoxicity. However, the results reported here do not exclude deleterious effects of T2 on a longer time scale as well as do not show that T2 acts in the same way in humans. PMID: 16014396 n=rats

Licit or did you cook this up yourself?

A 50% reduction in migraine severity is a pretty dramatic finding...I don't know that most people get this kind of result from any available medication.

Inhaled cannabis reduces self-reported headache severity by 47.3% and migraine severity by 49.6%, according to a recent study. The study also found no evidence that cannabis caused 'overuse headache,' a pitfall of more conventional treatments. The researchers did see patients using larger doses of cannabis over time, indicating they may be developing tolerance to the drug. Full Article

You still doing keto?