Towards Natural Mimetics Of Metformin And Rapamycin.
Aging (Albany NY). 2017 Nov 15;9(11):2245-2268. doi: 10.18632/aging.101319. Towards natural mimetics of metformin and rapamycin. Insilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA. Biogerontology Research Foundation, Research Department, Oxford, United Kingdom. Department of Biomedical and Molecular Science, Queen's University School of Medicine, Queen's University, Kingston, ON K7L 3N6, Canada. Life Extension, Ft. Lauderdale, FL 33308, USA. Laboratory of Molecular Radiobiology and Gerontology, Institute of Biology of Komi Science Center of Ural Branch of Russian Academy of Sciences, Syktyvkar, 167982, Russia. Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals-safer, naturally-occurring compounds-that mimic the anti-aging effects of metformin and rapamycin without adverse effects. We applied several bioinformatic approaches and deep learning methods to the Library of Integrated Network-based Cellular Signatures (LINCS) dataset to map the gene- and pathway-level signatures of metformin and rapamycin and screen for matches among over 800 natural compounds. We then predicted the safety of each compound with an ensemble of deep neural network classifiers. The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metfor Continue reading >>
Scientists Find Natural Mimetics Of Anti-cancer & Anti-aging Drugs Metformin And Rapamycin
Scientists find natural mimetics of anti-cancer & anti-aging drugs metformin and rapamycin Scientists at the Biogerontology Research Foundation, Insilico Medicine and Life Extension use Deep Learning-based Artificial Intelligence to Score natural compounds according to safety and gene- and pathway-level similarity to metformin and rapamycin IMAGE: This figure depicts an AI-driven drug discovery workflow schematic. view more Wednesday, Nov. 29, 2017, London, UK: Researchers from the Biogerontology Research Foundation , Insilico Medicine , Life Extension and other institutions announce the publication of a landmark study in the journal Aging on the identification of natural mimetics of metformin and rapamycin. Metformin, a common type 2 diabetes drug, and rapamycin, a common anti-rejection drug, have both been shown to have substantial anti-aging and anti-cancer effects in a variety of model organisms. However, both compounds have known side effects and are regulated drugs for existing disease indications, factors that problematize their off-label use as healthspan extending drugs. In this study, the researchers applied deep-learned neural networks to profile the safety and gene- and pathway-level similarity of more than 800 natural compounds to metformin and rapamycin, in an effort to identify natural compounds that can mimic the effects of these anti-cancer and anti-aging drugs while remaining free of the adverse effects associated with them. "Earlier this year we launched Young.AI, a comprehensive system utilizing the recent advances in deep learning for tracking a variety of aging biomarkers. I hope that the consumers using the Longevity A.I. will start using it. One of the goals of our group is to identify the combinations of molecules that achieve the desired ef Continue reading >>
Scientists Find Natural Mimetics Of Anti-cancer, Anti-aging Drugs Metformin And Rapamycin
Scientists find natural mimetics of anti-cancer, anti-aging drugs metformin and rapamycin November 29, 2017, Biogerontology Research Foundation AI-driven drug discovery. Credit: Insilico Medicine Researchers from the Biogerontology Research Foundation, Insilico Medicine, Life Extension and other institutions have published a study in the journal Aging on the identification of natural mimetics of metformin and rapamycin. Metformin, a common type 2 diabetes drug, and rapamycin, a common anti-rejection drug, have both been shown to have substantial anti-aging and anti-cancer effects in a variety of model organisms. However, both compounds have known side effects and are regulated drugs for specific disease indications, factors that problematize their off-label use as healthspan-extending drugs. In this study, the researchers applied deep-learning neural networks to profile the safety and gene- and pathway-level similarity of more than 800 natural compounds to metformin and rapamycin in an effort to identify natural compounds that can mimic the effects of these anti-cancer and anti-aging drugs while remaining free of the adverse effects associated with them. "Earlier this year, we launched Young.AI, a comprehensive system utilizing the recent advances in deep learning for tracking a variety of aging biomarkers. One of the goals of our group is to identify the combinations of molecules that achieve the desired effects," said Alex Zhavoronkov, Ph.D., co-author of the study. Their analysis identified many previously unreported metformin and rapamycin mimetics. In particular, they identified allantoin and ginsenoside as strong mimetics of metformin, epigallocatechin gallate and isoliquiritigenin as strong mimetics of rapamycin, and withaferin A as a strong mimetic of both. Add Continue reading >>
Avoid The Metformin Bandwagon
From diabetes to cancer, berberine matches - or beats - this patent medicine every time! As many know, metformin is the number one prescription medication for type-2 diabetes. The patent for the name-brand of this patent medicine, Glucophage®, expired years ago and as a result generic-brand competition (metformin) brought this patent medicine’s price down so that it’s relatively inexpensive, especially when compared with nearly any other medication still covered by a patent. Mainstream medical research has found other uses for this un-natural molecule, including (but not limited to) lipid, blood pressure, and insulin resistance lowering effects, anti-cancer effects, improvement of polycystic ovarian syndrome, combatting Alzheimer’s disease, and extending life span in mice. Surprising guests on the metformin bandwagon Some proponents of natural therapies – including, surprisingly, two nationally and internationally circulated health magazines – have climbed on the metformin bandwagon, writing articles about the “health benefits” of metformin, and even advocating that otherwise healthy people take this patent medicine every day as a preventive. They admit that there are known side effects, but write that these are few, and that the benefits outweigh the risks. If there aren’t any natural treatment alternatives that are as effective, or more effective, than a patent medicine or other un-natural molecule – especially in serious or life-threatening situations – then the use of a patent medication of course makes sense. But when there are natural alternatives that work just as well or better, the rule is – and always should be – to “Copy Nature.” Human bodies are formed from the molecules of planet Earth, and powered by the energies of this planet Continue reading >>
Towards Natural Mimetics Of Metformin And Rapamycin
Towards natural mimetics of metformin and rapamycin We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Towards natural mimetics of metformin and rapamycin Alexander Aliper, Leslie Jellen, [...], and Alex Zhavoronkov Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticalssafer, naturally-occurring compoundsthat mimic the anti-aging effects of metformin and rapamycin without adverse effects. We applied several bioinformatic approaches and deep learning methods to the Library of Integrated Network-based Cellular Signatures (LINCS) dataset to map the gene- and pathway-level signatures of metformin and rapamycin and screen for matches among over 800 natural compounds. We then predicted the safety of each compound with an ensemble of deep neural network classifiers. The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metformin), epigallocatechin gallate and isoliquiritigenin (rapamycin), and withaferi Continue reading >>
8 Natural Alternatives To Actos And Metformin
If you suffer from Type 2 diabetes, there is a good chance that you’ve had a discussion with your doctor about the prescription drug Metformin. It is often initiated at the diagnosis of diabetes and helps to reduce blood sugars in an effective way. The problem however with this solution is its inability to work for everyone. Additionally, many users of Metformin may find the side effects of this drug extremely bothersome. The first thing to remember is that the development of Type 1 diabetes is not your fault, no matter what your medical providers might have you believe. Diabetes is caused by your body’s inability to process, driving up your blood sugars. However, Type 2 diabetes (adult onset) can be avoided many times and even reversed with the right diet, exercise program and proper natural herbs and vitamins. Dealing with High Blood Sugar Levels Maintaining your blood sugar levels into acceptable ranges is critically necessary to maintain your quality of life, which means your routines are going to be changing no matter what you do. High blood sugars can cause nerve and kidney damage, so it is important to act now. Whether you want to avoid prescription medication, or suffer with current side effects, many natural alternatives exist for Metformin. These options may be able to effectively treat your diabetes and help you feel back in control again 8 Natural Alternatives to Metformin 1. Lifestyle Changes: For many that suffer with Type 2 diabetes, basic lifestyle changes are often the primary thing that is necessary for treatment of their disease. For many people, this means an increased level of exercise and an improvement in their overall nutrition. The goal of these lifestyle changes is to get on an effective weight loss plan that is combined with higher levels Continue reading >>
Berberine For Diabetes – Is It A Natural Alternative To Metformin?
Incidence of insulin resistance, obesity, and other metabolic diseases have reached massive proportions in our culture. The current popular glucose-lowering drug treatment, Metformin comes with some potential serious side effects. However, there is a natural Metformin alternative that can help the body efficiently process sugar, thereby being safer than pharmaceutical interventions. It’s known as Berberine. What is Berberine and Where Does it Come From? Berberine is a plant photochemical that’s found in several different plants, including goldenseal, European barberry, phellodendron, goldthread, Oregon grape, and tree turmeric. It possesses powerful anti-diabetic properties, as well as being anti-bacterial and immune system enhancing. As well as diabetes it can be used as a treatment for a number of other health problems including hyperlipidemia, heart disease, and cancer. It can regulate blood glucose, increase insulin sensitivity as well as metabolizing fats (burning fat). Berberine has been widely studied, with nearly 1000 studies published on it in the last 5 years alone. There is a body of evidence supporting it’s efficacy in lowering blood-glucose and increasing insulin sensitivity for both humans and animals. However, Berberine is not a new discovery. For thousands of years the Chinese and Ayurvedic communities has been aware of the amazing benefits of Berberine. The blood-sugar lowering effects have been documented in China and India for hundreds of years. Although it was primarily used for treating inflammation, infections, and diarrhea, as diabetes was not as common then as it is now (1). A Natural Substitute For Metformin? However, as the incidence of diabetes has grown, the recent studies have focused on it’s ability to treat the condition. The studi Continue reading >>
Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes. It is not associated with weight gain. It is taken by mouth. Metformin is generally well tolerated. Common side effects include diarrhea, nausea and abdominal pain. It has a low risk of causing low blood sugar. High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses. It should not be used in those with significant liver disease or kidney problems. While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes. Metformin is in the biguanide class. It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues. Metformin was discovered in 1922. French physician Jean Sterne began study in humans in the 1950s. It was introduced as a medication in France in 1957 and the United States in 1995. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Metformin is believed to be the most widely used medication for diabetes which is taken by mouth. It is available as a generic medication. The wholesale price in the developed world is between 0.21 and 5.55 USD per month as of 2014. In the United States, it costs 5 to 25 USD per month. Medical uses Metformin is primarily used for type 2 diabetes, but is increasingly be Continue reading >>
Metformin For Pcos? At Least Four Natural Methods Are Equally Effective.
Several medical research studies have shown that just changing your diet and lifestyle can be just as effective as taking metformin. For example, the Universidade de So Paulo in Brazil studied 40 women who had PCOS (polycystic ovary syndrome). Fifteen women took metformin for six months and 12 just improved their lifestyle. At the end of six months, the results were virtually the same for both groups. About 67% in each group had improvements in their menstrual cycle. Both groups had smaller waists and lost weight. Of course, taking drugs to manage your PCOS symptoms and improving yourlifestyle are not mutually exclusive! So you're into taking drugs, youcan do both! OK, so maybe you're wondering what a "lifestyle" consists of. For starters, it consists of a diet especially designed to rebalance your hormones , increased exercise, better management of chronic stress, and getting enough sleep. There are several compelling reasons why you should consider a more "holistic" approach using physical activity, healthy diet, stress management, and special nutrients. A healthy diet and lifestyle is just as effective as metformin (Glucophage). You may be able to reduce your dosage or eliminate it altogether. A healthy diet and lifestyle is ultimately less expensive. A holistic approach builds your health whereas drugs does not. A holistic approach does not have drug side effects and is safer than taking drugs. The role of healthy diet, exercise and stress management is extensively described in The Natural Diet Solution to PCOS and Infertility e-book. Studies have shown that these inexpensive measures are as effective as metformin -- and, they obviously have no side effects. If you improve your diet and increase your level of exercise, you may be able to reduce or even eliminate yo Continue reading >>
Berberine Is Superior To Metformin
New findings show that berberine has antiobesity effects and that … Metformin is a widely used first-line antidiabetic drug prescribed by doctors for the treatment of type 2 diabetes, particularly in the overweight and obese. By Will Block A new review focuses on several studies showing that the plant alkaloid berberine can lower blood glucose as effectively as the drug metformin at similar doses (500 mg, taken 3 times/day), and perhaps even better in some ways.1 Berberine is found in Coptis chinensis (goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Hydrastis canadensis (goldenseal), and Berberis aristata (tree turmeric). Traditionally, it has been used for more than 2500 years in both Ayurvedic and Chinese medicine, with growing interest in its effects in metabolic and cardiovascular disease in the Western world in the last decade. Berberine has a wide range of healthful uses that include cardiovascular, anti-inflammatory, and antimicrobial (it acts against bacterial diarrhea, intestinal parasites, fungal infections, Candida albicans, yeast, and possibly methicillin-resistant Staphylococcus aureus). Berberine for Diabetes Mellitus Type 2 As we have already reported (see “Take This Dye for Diabetes” in the November 2010 issue), two recent studies (also covered in the recent review) show the effectiveness of berberine compared to metformin for type 2 diabetes.2 In the first study, 36 adults with newly diagnosed type 2 diabetes were randomly assigned to treatment with berberine or metformin (500 mg 3 times/day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Metformin is a widely used first-line antidiabetic drug prescribed by doctors for the treatment of type 2 diabetes, particularly in the Continue reading >>
For The Love Of Berberine: What It Is And Why I Take It To Lower Blood Sugar, Bad Cholesterol, And Weight (plus 5 Faqs)
Since I saw my first patient in 1989, I’ve refined my approach to health and healing. Probably the biggest needle mover is my growing respect for plant medicine and its role in healing. My enthusiasm for berberine is in lockstep with my personal and professional experience prescribing herbs, but also as the evidence continues to mount about their relative safety and benefits. In this series, I will feature my favorite herbal therapies that you may want to consider, depending on your issues, and discuss with your integrative clinician. Our first herb is the herbal superstar known as berberine. When it comes to re-balancing your hormones, I believe in starting first with targeted lifestyle changes, such as upgrading the way you eat, move, and think. Fill the likely nutritional gaps. If that doesn’t work, try herbal therapies, and if you still are suffering, consider bioidentical hormone therapy. In my book, The Hormone Reset Diet, I recommend berberine as you finish the 21-day protocol, when you liberalize your eating. Berberine is insulin-sensitizing, anti-inflammatory, and anti-oxidant activity will help you stay out of harm’s way, if it’s used strategically and wisely. What is berberine? Berberine is a naturally-occurring yellow plant extract with a long history of medicinal use in Ayurvedic and Chinese medicine. Found in the roots, rhizomes, stems, and bark of various plants including goldenseal (Hydrastis Canadensis), barberry (Berberis vulgaris), goldenthread (Coptis chinensis), Oregon grape (Berberis aquifolium), phellodendron (Phellodendron amurense, and not to be confused with the unrelated household plant, philodendron), and tree turmeric (Berberis aristata). Historically, berberine’s rich yellow color made it valuable as a natural dye. What does berbe Continue reading >>
Paleo Diet, Inflammation And Metformin
I wish life were simple. I guess it is in a way, you live, you die. But the pesky in-between parts, the details can be decidedly non-simple. Heck, they might even be complex! The paleo diet, or more accurately the paleo template, which includes thinking about sleep, lifestyle, photoperiod and socialization, is simple on the surface: Food: Fish, fowl, meat, roots, tubers, fruits, veggies, and good fats. Socialization: Have a solid support network. Dont Go Ted Kaczynski on us. Photoperiod: Get up with the chickens, go to bed with the same. See, simple! Well, until folks want to know how many carbs they need (it depends) if fruit is good or bad (again, it kinda depends) what constitutes good fats. These details can get murky, but its not that hard to navigate folks through the Paleo Template to help them dial things in for best effect. With that in mind, if you need extra help dialing things in, check out Chris Kressers Personal Paleo Code. Be your issue autoimmunity, fat loss or you just want a little hand holding, that program has the goods. With the infomercial out of the way, we can get down to the things I really want to talk about in this installment: the paleo diet, inflammation and the drug metformin. This will be at once simple, as Im going to present what I suspect is the root cause of a host of issues related to inflammation, insulin resistance, cancer, autoimmunity and neurodegeneration; namely intestinal permeability (leaky gut in the hippy circles). This is simple in that we may have a common mechanism that underlies all of these conditions. It is complex in that we have a myriad of ways to induce permeable gut and once that happens the ensuing metabolic and immunologic cascades can be tough to keep track of. If you asked me 10 years ago Whats the cause of a Continue reading >>
Can Metformin Extend Your Life?
A new research effort will try to see if the diabetes drug combats the effects the aging Three or four years ago, a buzz started building that metformin could be a potential fountain of youth. In 2011, a group of researchers in oncology in St. Petersburg, Russia, found that metformin could prevent the advancement of cancer in mice, thereby increasing their lifespans . In 2012, several online health advocates passionately accused the FDA of sinister motivations for preventing the makers of metformin from advertising it as an anti-cancer and anti-vascular disease medicine. There appears to be no such conspiracy. This year, the FDA registered a human trial of metformin for a placebo-controlled study involving people with diabetes and those without to test whether the drug can promote overall longevity. The trial will be undertaken at the Einstein College of Medicine at Yeshiva University in New York, and is at publication time still recruiting participants. If the results prove favorable, it will mark another dynamic chapter in the storied history of the drug. Metformin is said to have first been created in France in the 16th century, when it was made from an extract of the plant galega officinalis, known as goats rue or French lilac. As an herbal remedy, it was used in treating a urinary disorder with a name derived from Greek that meant sieve, which may in fact be whats known in modern times as diabetes insipidus. French pharmacy labs began to make a synthetic formulation in the 1920s, but then, according to the lore, the discovery of insulin overshadowed it as a more promising diabetes remedy. Efforts to develop the synthetic version diminished in the worldwide financial fallout from the 1929 Wall Street crash, and was abandoned during WWII German occupation of France. Continue reading >>
The Surprising Truth About Metformin
The “natural” blood-sugar remedy that had been sidelined for far too long What I’m about to tell you may be shocking. And it’s sure to ruffle the feathers of many of the “natural know-it-alls.” But the science is clear, so I’m not afraid to say it: If you have unmanaged Type II diabetes, you should consider the drug metformin as a first line of treatment. And you won’t get the full story anywhere else, since the natural health industry wouldn’t be caught dead recommending a drug. So, please allow me to do the honors here… Think of it as your emergency “get out of jail free card” Diabetes is deadly. High blood sugar coursing through your body destroys your eyes, kidneys, heart, brain, and more. So the sooner you bring it down the better. (Just like high blood pressure, for which I also recommend tried and true medications as a first-line treatment for unmanaged hypertension.) And in this case, the science is clear—the drug metformin has been proven safe and effective for most people. And since it’s now a generic drug, it’s highly cost effective, too. Now don’t get me wrong…I’m not saying diet and exercise isn’t important. In fact, they’re the best means for preventing and even reversing Type II diabetes entirely. Something metformin can’t do. And there are certainly dietary supplements that can help with maintaining healthy blood sugar (like berberine). But Type II diabetes doesn’t develop overnight. And let’s face it, changing the habits and consequences that got us there in the first place isn’t an overnight task either. So if you need additional help, this is one rare instance where you shouldn’t be afraid to look at a mainstream therapy. And when an option this effective comes along to help kick-start your efforts saf Continue reading >>
Biguanide - An Overview | Sciencedirect Topics
The biguanides are derivatives of guanidine, a naturally occurring substance found in vegetables such as turnips and cereals:Biguanides are usually supplied as polymers in the salt form, mostly as the hydrochloride. Caroline Day, Clifford J. Bailey, in xPharm: The Comprehensive Pharmacology Reference , 2007 The biguanides are derivatives of the compound biguanide (guanylguanidine) that exert a blood glucose-lowering effect in type 2 (non-insulin dependent) diabetes mellitus. The main biguanides are metformin (dimethylbiguanide) and phenformin (phenethylbiguanide), which were described in 1957 and buformin (butylbiguaninde), which was described in 1958 Schafer (1983), Bailey (1992). Phenformin and buformin were withdrawn from clinical use in most countries in the late 1970s due to a high incidence of associated lactic acidosis. Metformin, which has a much lower risk of lactic acidosis, is used widely in the treatment of type 2 diabetes. Biguanides do not increase plasma insulin concentrations and do not cause severe hypoglycemia, hence they are regarded as antihyperglycemic (rather than hypoglycemic) agents. Sigal Soferab, ... Zecharia Madara, in Nutrition in the Prevention and Treatment of Abdominal Obesity , 2014 Biguanides (mainly Metformin) are widely prescribed antihyperglycemic agents that suppress hepatic glucose production, increase peripheral glucose uptake, and moderately reduce LDL cholesterol and triglyceride levels. Glucose control with the aid of biguanides appears to decrease the risk of diabetes-related complications, and is not associated with weight gain. This medication is reportedly associated with fewer hypoglycemic episodes than other lines of drugs. Biguanides activate AMPK, thus improving insulin signaling, whole-body energy balance, and the meta Continue reading >>