Since Semaglutide arrived on the pharmaceutical scene, a medication originally developed to treat diabetes, the drug has morphed into the anti-obesity medication of choice for millions.
Semaglutide, developed by the Danish pharmaceutical company, Novo Nordisk, is available under two names: Ozempic and Wegovy. A similar drug called Tirzepatide, from U.S.-based Eli Lilly, is sold as Mounjaro and Zepbound. The results of taking these drugs related to weight loss have been astounding.
For people classified as morbidly obese, the taking of these drugs has given them a new lease on life. Losing weight has reversed prediabetic diagnoses.
In 2021, an article in The New England Journal of Medicine described the results of a double-blind trial using semaglutide and a placebo. All participants fit the body-mass profile of obesity. Over 68 weeks, both semaglutide and the placebo were administered using subcutaneous injections. Weight loss results for those taking semaglutide averaged 14.9%. Those on the placebo lost 2.4%. Some participants went off the semaglutide during the trial because of its side effects.
The trial didn’t follow the participants after the 68 weeks. What would have been interesting is to see how many who stopped taking semaglutide saw their weight loss vanish.
In an article appearing on ABC News on March 6, 2024, health reporter Jonel Aleccia wrote about the trials of those who have been prescribed these weight-loss drugs and then gone off them.
Obesity is a chronic condition treated by doctors who are weight loss specialists. Obesity leads to chronic conditions such as diabetes and high blood pressure. Obesity can lead to strokes, congestive heart failure, and heart attacks.
Currently, in the U.S. more than 3 million prescriptions of Semaglutide and Tirzepatide drugs are dispensed monthly. In worst cases, these drugs cause a condition called gastroparesis with symptoms including severe nausea, vomiting, and abdominal pain. That’s why many who have been prescribed these drugs try to get off them after achieving their targeted weight loss. Some try to combine exercise with reduced use of the drugs. Or they cut down to twice-monthly injections. However, obesity researchers note, that used intermittently, Semaglutide and Tirzepatide don’t work very well.
Administered weekly these drugs can cost$1,000 to $1,300 U.S. per month. This puts a financial strain on a segment of the population that is most susceptible to obesity, the poor. That’s because low-income diets often include cheap, high-fat, high-sugar fast foods. As well, low-income earners may not have health insurance coverage to pay for the drugs making their cost an added burden.
So going off the drugs and hoping the benefits will last ignores the reality of obesity as a chronic condition. The ABC article notes: “Many people dropping off the medications report a sharp rise in symptoms of obesity. They include so-called food noise or intrusive thoughts of food; raging hunger; and decreased feelings of fullness when they eat.”
Why is this happening? Dr. Amy Rothberg is a University of Michigan endocrinologist who directs a weight-management and diabetes treatment program. She told ABC News, “These drugs are just a super-suppressor of…native signals and we should expect that’s going to occur” referring to increased weight gain.
When I was diagnosed as being prediabetic, my doctor offered me Ozempic. I read the literature and decided to stick to portion control, less meat, and more exercise in my life. I haven’t been sorry.
]]>I’ve been taking statins for more than 14 years. Finding the right pill was torturous because of the side effects I experienced. The first statin I was prescribed made me feel like someone was punching me in the kidneys. It took several weeks after I stopped taking the statin for the pain to go away. When I was given a second option, the pain in my lower back was more manageable but it wasn’t until a pharmacist suggested I take a CoQ10 supplement along with the statin, that I finally found relief. My cholesterol levels have been under control now for a long time.
My wife recently was prescribed a statin for high cholesterol. Her side effects have been more alarming and she has had the prescription changed and twice has gone off the daily pill taking.
My brother-in-law uses an alternative injectable medication to control his cholesterol levels. He couldn’t tolerate statins either.
So much for putting the stuff in drinking water.
Combatting high cholesterol, however, is vital because as a chronic condition, it can double your risk of having a heart attack or stroke.
Recently, I read about an American company working on a vaccine to treat high cholesterol. The company is Vaxxinity, Inc., and so far, in non-human primate studies, their product, VXX-401, is demonstrating good results in treating hypercholesterolemia (high cholesterol) and preventing atherosclerotic cardiovascular disease. The study results have recently been published in The Journal of Lipid Research. The company is now in Phase 1 clinical trials.
VXX-401 vaccine, when administered to cynomolgus monkeys, showed that it stimulated their immune systems to produce antibodies to target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), a natural protein associated with the production of cholesterol in the body. By blocking PCSK9, the vaccine lowered cholesterol levels in the blood.
It is a waxy substance found in all cells in the body. It plays a significant role in the production of hormones, vitamin D, and bile acids. It comes in two forms: Low-Density Lipoprotein (LDL-C) and High-Density Lipoprotein (HDL).
The former, LDL-C, has been given the moniker “bad cholesterol” because when there is too much of it, it can build up on arterial walls where it can block blood flow and compromise the heart. Both cholesterols are produced in the liver and small intestine.
HDL, the “good cholesterol” controls LDL-C levels in the blood helping the body to get rid of too much.
High LDL-C levels can have a genetic component, but most often lifestyle, diet, and weight are the cause.
VXX-401, so far, has demonstrated it reduces LDL-C levels on average by 44% in animal studies. It also appears to be well tolerated. Across three separate preclinical studies in cynomolgus monkeys, VXX-401 induced a strong and durable antibody response against PCSK9 and robust, sustained reduction of LDL-C over time. Prolonged exposure with VXX-401 resulted in an average of 44% LDL reduction. VXX-401 was well tolerated and did not induce any toxicity or pathology beyond mild injection site reactions. These results suggest that VXX-401 could be a safe and effective anti-PCSK9 immunotherapy.
VXX-401 was designed using Vaxxinity’s proprietary synthetic peptide vaccine platform Mei Mei Hu, Vaxxinity’s CEO, in a press release announcing the publication of the latest non-human primate results stated, “Despite multiple approved medications for LDL-C reduction, heart disease remains the number one killer in the world. A cholesterol vaccine like VXX-401 may provide a cost-effective and widely deployable solution that could potentially benefit hundreds of millions of people at risk. A well-tolerated intervention that people can start early in life, and remain on for many years, lowering the cholesterol ‘area under the curve,’ has the potential to help us win the fight against heart disease.”
Phase 1 of the clinical trial of VXX-401 is focused on determining the safety of its administration and how well it is tolerated in humans. We should see preliminary results by late summer.
Vaxxinity isn’t just looking at treating hypercholesterolemia. The company’s mission is to democratize healthcare through the pioneering of a new class of medicines aimed at disrupting existing treatments for several chronic diseases while reducing the cost to patients. The company is using its novel synthetic peptide immunotherapy vaccine candidates to treat Alzheimer’s, Parkinson’s, migraine, and COVID-19.
]]>Permafrost covers 20% of the Northern Hemisphere. By definition, it is ground that stays frozen for at least two consecutive years. In the Arctic, Antarctica and alpine areas, permafrost persists.
Some areas of permafrost go through seasonal partial thaws. Much never does until recent years as polar regions and mountainous areas are increasingly impacted by global atmospheric warming.
What’s stored in permafrost is about what we need to be concerned. It contains an enormous amount of biomass, which is a natural carbon sink. That’s a good thing as long as the permafrost doesn’t melt. But biomass also contains what is being referred to as zombie viruses and bacteria.
In 2016, an anthrax outbreak in Siberia killed thousands of reindeer. The cause was traced to thawing permafrost that exposed a 75-year-old infected reindeer. The thaw had revived Bacillus anthracis, the anthrax bacterium that unfortunate reindeer ingested or inhaled.
It could just as well have been:
Here are some recent permafrost discoveries.
Today, scientists are increasingly concerned about the potential pandemic threat coming from the equatorial and polar areas of the planet. We know that mosquitoes, ticks, fleas and other wildlife can be common carriers of many equatorial diseases posing a threat: Malaria, Dengue, Zika, and Chikungunya, to name a few. But now we need to be on guard for viruses and bacteria emerging from the permafrost.
Today, we have a vaccine for smallpox and one for bubonic plague. We annually update influenza vaccines. But the zombie viruses and bacteria that have been buried in permafrost pose a threat because we have no recent exposure to them, meaning we won’t immediately have medical treatments to contain outbreaks. We won’t have built-up immunity either. That’s why there is an emerging Arctic monitoring network of scientists looking for viruses and bacteria that could come from permafrost and meltwater.
Although thawed permafrost contains traces of genomic information from viruses, Dr. Jonathan Stoye, a retrovirus researcher at the Francis Crick Institute in London, UK, notes that the “inherent instability of the viral nucleic acids” makes the likelihood of infection transmission less. He believes the greater threat would come from an awakening bacteria.
COVID-19 may have done humanity a favour. Our rapid response to it including new vaccines, and comprehensive global reporting, has us much better organized to recognize and fight an outbreak. Add permafrost to the list of disease vectors that include mosquitoes, ticks, fleas, rodents, snails, monkeys, bats, and other forms of wildlife posing a pandemic-starting threat.
]]>Periodically, cures for tinnitus appear in the media. They can be classified into four categories: sound therapy, behaviour therapy, medication, and surgery. The first two involve retraining the brain. By focusing on the sounds, some therapists believe you can learn to ignore them. Others believe that using cognitive-behaviour therapy can desensitize you to the sounds. Neither of these two have worked for me. I haven’t gone the medical or surgical route and don’t intend to.
Medical professionals who deal with tinnitus include audiologists and otolaryngologists. When you talk to them about the condition, most will admit that no treatment for tinnitus eliminates it in its entirety. Trying to measure the condition is nearly impossible with the advanced medical technologies we have today. Instead, hearing specialists only have a patient’s descriptions of the condition to use for treatment guidance.
In December of last year, I posted to this blog site an article on new research into the cause of tinnitus. I wrote about a technological cure called Lenire which had received US FDA approval. It featured 30-minute sessions which involved a tongue pulse stimulation device designed to retrain the brain to ignore the condition.
Lenire is an example of a medical device that uses bimodal neuromodulation which refers to a simultaneous or sequential application of two different neuromodulation techniques to target specific neural circuits in the brain and modulate or switch off the transmission of signals like the sounds experienced by those with tinnitus.
Bimodal neuromodulation today is being used with a combination of deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) to treat Parkinson’s disease, a neuromuscular disorder. Another example being used to treat neurological disorders involves combining optogenetics and chemogenetics. Optogenetics uses a technique to genetically modify neurons to express light-sensitive proteins to precisely control neural activity related to light. Chemogenetics activates genetically engineered receptors to control neural activity. The combination is showing promising results in treating epilepsy, addiction, and depression.
An article in The Washington Post that appeared on January 19th of this year caught my attention and led me to revisit the subject. It described the latest bimodal neuromodulation treatments for tinnitus. One of them was Lenire which uses a combination of headphones playing a range of high and low sounds along with background noises while wearing a mouthpiece that sends electrical pulses to the tongue. In theory, the combination causes our brains to focus more on the high and low sounds rather than on the background tinnitus.
According to the Washington Post article, Lenire is one of three bimodal neuromodulation devices and treatments being hailed as game changers in tinnitus treatment. Neosensory’s Duo uses a haptic wristband to produce vibrations that get transmitted through the skin which when combined with synchronized sounds creates a similar treatment outcome. A third technology being developed at the University of Michigan delivers electrical pulses to the neck or jaw while the wearer listens to sounds through a headset.
These bimodal neuromodulation treatments are very different from anything offered to tinnitus sufferers. Studies reported in peer-reviewed journals, however, have used tiny sample sizes for tests. In the case of both Lenire and Duo, these studies have not used a placebo-control group as a means of comparison. Does that matter? As one tinnitus researcher described the Lenire and Duo results, the patients enrolled in these studies may have been experiencing a placebo effect, just being grateful for having been offered any kind of treatment. As one sufferer described tinnitus, “You get to the point where you’d give up your right arm to get rid of the noise.” I couldn’t concur more.
]]>A 2022 study published in the Lancet used health statistics from 2019 to show that 7.7 million deaths globally that year were linked to 33 types of bacterial infections. The number was only second to ischemic heart disease as the cause of death in humans. The five leading bacteria include Staphylococcus aureus (SA), Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa accounting for almost 55% of the total.
The MIT researchers used AI to select and predict the best molecules for producing drug compounds that could work on killing SA. James Collins, Professor of Medical Engineering at the MIT Institute for Medical Engineering and Science, describes deep learning as “time-efficient, resource-efficient, and insightful.”
The results appear in the December 20, 2023 issue of Nature, and show that the deep-learning identified drug compounds kill methicillin-resistant SA. The researchers also report that they can see what the deep-learning AI is doing as it searches through millions of molecular combinations to find candidates that show good potency and very low toxicity when in contact with human cells to make them good antibiotic candidates.
SA causes skin infections, sepsis, a fatal bloodstream infection, and pneumonia in more than 80,000 people in the United States every year leading to 10,000 deaths. It is not the only targeted bacteria the MIT researchers are looking at through the lens of AI deep learning. Recently they identified a compound to treat the drug-resistant bacteria, Acinetobacter baumannii (AB) commonly found in hospitals.
Before the discovery of a potential drug compound to deal with SA, AI searches suffered from the “black box” effect. Black boxes don’t reveal how they draw their conclusions. But with SA research the deep-learning AI was wide open to see the connections and calculations the neural network was doing. The use of expanded datasets was key to training the AI and used 39,000 compounds and their chemical and molecular structures. Shuffling the atoms and bonds around also allowed the AI to discern in percentages the probabilities of antibacterial success.
A Monte Carlo algorithm was used. It relies on repeated random sampling to obtain numerical results and gets its name from the Monaco casino where it was first used to simulate roulette games. Monte Carlo works by generating large numbers of random samples to determine the probability of a desired output. The AI-deep learning used the algorithm to generate estimates of a molecule’s antimicrobial activity and predictions about which substructures of the molecule likely accounted for the activity. To predict human toxicity to identified compound candidates, the researchers trained three additional deep-learning models. The combination of these AIs provided a short list of desirable compounds that not only killed SA but also did no harm to humans.
Twelve million commercially available compounds were reviewed by the AI. It identified five class types exhibiting the right chemistry. A total of 280 were available for purchase off the shelf. These were tested with two showing considerable promise. Each showed in the laboratory that they could disrupt SA bacteria in infected mice by disrupting the electrochemical gradient across cellular membranes, critical to cell function. In exposure to human cells, there was no disruption.
The MIT results have been shared with Phare Bio, a nonprofit company that has participated in the project. The company and MIT will work on turning these promising compounds into a drug for clinical use. They will continue to work using AI deep learning to discover other candidates to fight drug-resistant bacteria. This should lead to new antibiotics to fight bacterial infections that no longer respond to the drugs we have in our current medical arsenal.
]]>What is BMI? The American Centers for Disease Control (CDC) defines it as a number calculated using a formula that combines height and weight.
A confession from me: Last spring my BMI climbed over 30. I was obese. My blood tests indicated I was prediabetic. My doctor offered me a pharmacological remedy rather than dieting and exercise. She handed me a brochure about Ozempic and told me she was getting great results with other patients.
I asked her if Ozempic was a diabetes treatment. She said yes, but the side effect was rapid weight loss. I told her I would think about it. A diabetic friend prescribed Ozempic dropped weight faster than I had ever seen anyone do before. But what accompanied the weight loss was severe nausea, vomiting, diarrhea, and a change in appearance. I’m not talking just about changes to body shape, but also to his face making him appear much older.
I decided to decline my doctor’s offer and forego the quick fix. The cost was another deterrent but I will talk about that later in this posting. I changed how I eat using portion control. I then added swimming to my activities when we moved to an apartment with a pool. Today, I swim 1.6 kilometres (1 mile) every other day. My weight has dropped steadily and my BMI no longer has me as obese. I’m still overweight but it steadily is coming down. Finally, my recent blood tests indicate I’m no longer pre-diabetic. I intend to continue down this path.
The acceptance by modern society to treat many medical complaints, and even things not medical, is to look for a drug. Ozempic and other drugs classified as semaglutides or glucagon-like peptide 1 (GLP-1) agonists are the latest way modern society is attacking bad eating and living habits. We overeat and we are not active enough. During the pandemic with lockdowns and people working from home, overall BMIs went way up.
Being overweight is bad but being obese produces many more self-inflicted wounds. Obesity causes higher incidents of diabetes, heart and liver disease, high blood pressure, cancer, osteoarthritis, gallstones, high cholesterol, sleep apnea, reproductive health issues and more.
Treating obesity through diet and exercise according to the National Institute of Health in best-case scenarios produces an average weight loss of between 5 and 10%. Keeping the weight off, however, is never guaranteed. I am one of those people who has fought being overweight for much of my adult life. I have tried diets, and calorie restrictions, and have seen wildly swinging losses and gains over the years. The only meat, vegetables and fruit diet worked for me for a while. But you can’t stay on a diet that excludes carbs forever. Eventually, you will want to eat a toasted bagel.
So why not take the drug panacea offered to treat the condition? That’s what millions with obesity have decided to do, with GLP-1 agonists taking the planet by storm. Ozempic has been joined by other new brands including Wegovy, Rybelsus, Trulicity, Mounjara, Saxenda and Bydureon BCise.
I am sure, with obesity now no longer a weight condition but rather a disease, it will, like its predecessor disease, erectile dysfunction and cure in the form of Viagra become the driver of profit margins for biopharmaceutical firms for the foreseeable future.
When Viagra was first being developed by Pfizer it hoped to use it to treat high blood pressure and angina. It turned out it didn’t do either very well but it had an interesting side effect. It caused erections in male clinical trial subjects.
Could the side effect be a cure for something else? Pfizer decided to turn having and not having erections into a thing. When young, sexual potency is at its highest. It doesn’t last forever and by age 40, 40% of males experience erectile declines. This increases by 10% per decade as men age. Not all changes to erections are related to aging. In some cases, they are indicators of serious medical conditions.
Pfizer, however, having invested heavily in developing Viagra, chose to create erectile dysfunction as a disease. An ad campaign was hatched to promote the disease and the cure. Sales soared.
Ozempic’s right of passage is far more legitimate than Viagra’s. Obesity is a real problem. Treating it with drugs in the past has been problematic. Amphetamines and diuretics were the choices back in the 1950s, but they came with significant health risks.
The search for an effective alternative took decades until GLP-1, a 30-amino acid peptide hormone was identified in L-cells that reside in our intestinal tract. L-cells secreted glucagon which affected blood sugar levels. If GLP-1 could be isolated and used like insulin, it could become a way to control Type 2 Diabetes. But to perfect the drug took more than 30 years to achieve.
The first GLP-1 agonist drug to get U.S. Federal Drug Administration (FDA) approval was Byetta in 2005. Victoza came five years later. Both were approved for treating Type 2 diabetes. Two years ago Ozempic followed aimed at treating Type 2 diabetes while helping diabetics to lose weight. Ozempic clinical trials produced weight reductions of 15% over 16 months.
Since then, the advertising campaign asking “Is Ozempic right for me?” has led to soaring usage as a weight-loss drug. But there is more. Now, because of results obtained in large-scale clinical trials, GLP-1 agonists like Ozempic are being prescribed for treating heart failure. Clinical trials have shown that GLP-1 agonists delay kidney disease in patients with diabetes. There are even clinical trials with GLP-1 agonists to cure drug addiction, alcoholism, and nicotine dependency. What do GLP-1 agonists do to make it work on so many different medical problems? GLP-1 binds to receptors in the brain related to pleasure seeking. So if not food, why not wine, recreational hard drugs, opioid addiction, and cigarettes? And because GLP-1 agonists have an influence on inflammation within the brain, clinical trials for treating Alzheimer’s and Parkinson’s disease are also underway.
The body weight loss benefits for many taking GLP-1 agonist drugs outweigh the side of nausea, vomiting, and diarrhea. But there are side effects that are showing up that cannot be ignored. They include incidents of intestinal obstruction and pancreatitis.
Then there is the “forever” drug issue. There is a reasonable fear of Ozempic rebound happening with those taken off the drug. Recent studies show that after stopping its use for a year the weight returns.
Finally, there is both the delivery and cost of Ozempic, which if you don’t have health benefits or a drug plan can run to US $1,000 per month. The delivery method is a weekly self-administered injection. Only one of the GLP-1 agonists, Rybelsus, is a pill to be taken daily. But even it costs $1,000 per month.
]]>The US $101 million raised so far will be awarded to solutions that treat the conditions that limit healthy lifespans. The contest will last for seven years. Novel therapies to stop ageing-related diseases, eliminate muscle and bone mass loss, and address mental acuity issues will share the money.
Peter Diamandis, Founder and Executive Chairman of the XPrize, states, “Adding decades of health is the greatest gift we can offer humanity. I believe that converging exponential technologies will enable us to make 100 years old the new 60.”
Currently, medicine is focused on treating injuries, illnesses and diseases. This is a reactive model to extend life. It is not proactive to improve the quality of life and reduce the risk of chronic age-related diseases. And yet, our current medical model has doubled global life expectancy from where it was at the dawn of the 20th century.
The problem isn’t one that we are living longer, but rather that we are living longer with chronic illnesses in the latter part of our lives that leave us in poorer health. The challenge this represents as the world’s population ages could overwhelm healthcare as practiced today. By 2050, the number of 60-year-olds as a percentage of total world population is expected to grow from 12 to 22%. It is, therefore, urgent to find solutions to extend our healthy lives for more years. This will bring revolutionary change to the ageing experience.
Although Peter Diamandis talks about extending the human lifespan well beyond where we are today, the XPrize Healthspan’s focus is very different. It is less about longevity, and more about quality of life as we age. It is about eliminating the degradation that accompanies us as we grow older. It’s about developing a better understanding of the biomarkers of ageing and developing cost-effective therapies to restore musculoskeletal strength, cognition and immune function for a minimum of 10 years, with an ultimate goal of 20, for those between the ages of 65 and 80. It’s about ensuring that healthcare has the means to support the therapies and services coming out of XPrize Healthspan. What it is not about is extending the human lifespan to 150 or beyond.
All entries competing for the XPrize Helathspan will provide along with their novel therapies, one-year clinical trials involving people between the ages of 65 and 80 who are generally healthy even though they may be experiencing age-related functional declines. Examples of functional declines include slower walking speeds, more difficulty getting up from a sitting position, climbing stairs, and cognitive memory challenges. The obvious challenges in this age group range are issues like mobility-related falls, or the onset of Alzheimer’s and other dementias, as well as cardiovascular disease and cancer.
Novel therapies include drugs, biologic, devices, nutritional supplements, and dietary changes either alone or in combination. The drugs could be new or repurposed. The participants in the competition may come from current biotechnology companies, universities and hospitals, or from anyone anywhere. Governments are not allowed to enter the competition.
Peter Diamandis has stated in the past, “The day before something is truly a breakthrough, it’s a crazy idea.” Was it crazy to think about how semaglutides, developed for treating Type 2 Diabetes, have become a novel therapy for dealing with obesity because physicians noticed dramatic weight loss in patients taking the drug?
When you realize that obesity is one of the leading contributors to cardiovascular disease, cancer and shortened lifespans, you can see how crazy can turn into a breakthrough.
Today, 32% of Americans are overweight. Of those, 40% are obese. A drug developed to treat diabetes may do more to treat obesity than all the diets and exercise programs ever instituted in the past. As a person about to turn 75, I will be very much engaged in watching the progress made as this competition unfolds.
]]>Ozempic and Wegovy are self-administered injectables. Rybelsius is a pill. The drug classification is called a Glucagon-Like Peptide-1 Agonist. These are administered to patients along with advice to use with dieting and more exercise. These drugs control blood sugar levels making them effective for the treatment of diabetes. They can also be used to prevent major cardiovascular events such as heart attacks and strokes.
Earlier this year I was diagnosed as pre-diabetic. My blood sugar levels were above the normal range. In the three-plus years of COVID-19, I had gained over 15 kilograms (33 pounds). That’s when my new and very young family doctor offered to put me on Ozempic telling me she was seeing great results in terms of weight loss and reversing blood sugar levels. I knew people who had been put on Ozempic after being diagnosed with Type 2 Diabetes. They described the side effects which included significant weight loss along with some very negative effects. They suffered from nausea, extreme bowel discomfort, vomiting, diarrhea or constipation. I politely told my doctor, no thanks. Instead, I went on a diet and exercise program and have shed all the weight in the last six months. I am no longer pre-diabetic.
The World Health Organization (WHO) describes obesity as one of the most neglected public health problems. Being overweight is malnutrition’s opposite of which the latter is related to food insecurity. But obesity which the WHO calls globesity is a growing threat not just to Global North countries but also to those in the Global South.
Close to 2 billion out of nearly 8 billion today on this planet are considered overweight with 13% of adults classified as obese. In the United States today, 34% of adults and 15 to 20% of children and adolescents are obese.
Diet and exercise, plus a plethora of pills have been the traditional ways humans have approached weight loss. This has spawned a global weight-loss industry which in 2021 was valued at US $224 billion annually with projected growth to $405 billion by 2030.
Semaglutides have made Novo Nordisk a very rich company and possibly the biggest disrupter to the weight-loss industry. The side effects, however, remain the biggest inhibitor to growth in use. Based on current sales, however, it appears doctors and patients have fully bought into using semaglutides to drop significant body mass.
At the University of Massachusetts Amherst, S. Thai Thayumananavan, Professor of Chemistry and Biomedical Engineering, has invented a treatment for obesity and Type-2 Diabetes using a nanogel infused with a synthetic thyroid hormone or thyromimetic. Thyromimetics are drugs first developed to treat liver disease. But in this case, they are being used to treat obesity, high cholesterol and metabolic disease.
The test subjects for the study were mice fed a high-fat diet for weeks. They soon became obese. When given the thyromimetic packaged inside a nanogel and delivered daily by intraperitoneal injection (the needle goes directly into the liver, a much deeper injection than a typical vaccine) the mice quickly lost weight even though they were still being fed a high-fat diet.
Delivered this way, the thyromimetic activates the beta receptor hormone which causes fat oxidation, reverses cholesterol levels and increases metabolic rate. Originally intended for liver disease treatment, the results point to a “nanopartical-mediated pharmaceutical” alternative for treating weight loss.
For this to become a weight loss treatment, the delivery mechanism will have to be less invasive than intraperitoneal injection. If this issue can be solved, then move over semaglutide, you have a strong competitor in the wings.
The study results were published in August this year in an issue of PNAS Nexus, a journal of the National Academy of Sciences of the United States.
]]>Genetics is a fundamental part of our understanding of who we are as a species. Genetic variation, however, causes changes we call mutations that subsequently affect future generations. Good, bad, or ugly, mutations play a critical role in our evolution. Some genetic mutations negatively impact our health. Some affect how we process nutrition.
Genetics isn’t the lone player in our life health experience. Epigenetics has a role to play as well. Current research is uncovering nutrition-affecting mutations that play a greater role in our health, and how what we eat, where we live, and other environmental factors can play a role in altering gene expression and becoming the heritable triggering factor of mutations seen in following generations.
Genetic mutations are not uncommon. Hundreds of genetic mutations cause a variety of effects, some well-known, others not so much. Often, people associate genetic mutations with cancers and other rare diseases, but mutations are responsible for many other conditions and observed traits. Not all are welcome. This is particularly true when it comes to nutrition and gut health. Genetic mutations are responsible for so many of the nutritional issues that a substantial portion of humans face.
From a nutrition perspective, a mutation that impacts nutrient intake can lead to a complete and total lifestyle change. For instance, there are a variety of mutations that impede the body from processing proteins we ingest. Lacking the ability to absorb proteins can impact proper growth and function. A chronic lack of protein can lead to limited muscle mass, muscle weakness, low blood pressure and heart rates, and slow recovery from injuries.
Another common genetic factor so many face is related to nutrition and cholesterol. High cholesterol runs in families. It can lead to a greater likelihood of a heart attack or stroke at a young age. You can try to manage high cholesterol through lifestyle changes such as eating a low-fat diet, doing more cardio exercise, and managing your weight. Advances in DNA editing, however, may start to change the way we deal with cholesterol.
Cholesterol comes in two forms: HDL and LDL. HDL stands for high-density-density lipoproteins. LDL stands for low-density lipoproteins. When you have a blood test to check your cholesterol levels, each type is measured. Think of HDL as the good, and LDL as the bad. High HDL levels protect us from heart attacks and strokes. High LDL levels lead to the narrowing of arteries and increase the risk of heart attacks and strokes. High LDL cholesterol levels are linked to obesity which may have genetic roots. For patients with obesity, however, modifying their lifestyles can introduce epigenetics into the health equation.
What is epigenetics? It is the story of cause and effect, that modifying behaviours or changes to your environment can impact.
Epigenetics studies how behaviour and changes in the environment impact how genes work. It is proving to be an important addition to our study of our health and the role genetics plays. Epigenetic profiles, today, are being used to not only predict disease risk but also how long we will live. An epigenetic lifespan predictor called DNAm GrimAge is an epigenetic clock that can accurately predict how long we will live, barring accidents, from testing umbilical cord blood taken from a newborn.
How epigenetics impacts obesity looks at the influences of environment and lifestyle including what you eat and how that alters gene expression. Essentially, the genes in your body take regulatory cues from the environment in which you live. How they do so is heritable. That means your genetic makeup can be inhibited or activated by environmental factors.
When it comes to obesity, your diet and gut microbiota, together with environmental factors such as where you live and how sedentary you are, influence the expression of certain genes. In turn, this influence contributes to things such as cholesterol levels and how susceptible you are to various diseases.
Like genes, epigenetic mechanisms affect health. Your microbiome provides a good example of how this works. Microbiota are inextricably linked with mental and physical health. Your microbiome is shaped by who you live with, your mother’s microbiome (and how she gave birth to you), antibiotic usage, the community in which you live, as well as what you eat. Your microbiome affects gene expression. That’s why what you choose to eat can be consequential.
Diet is a strong epigenetic influencer on gene expression and mutation. Some research suggests that a healthy diet plays a role in limiting the impact of mutations, possibly even hiding their effects. As we better understand epigenetic diet influencers, it could play a role in helping us to develop customized nutritional plans that will manage genetic changes.
Aside from cholesterol, scientists are discovering all sorts of nutrition-based outcomes that are related to genetics ranging from obesity to maintaining a strict vegetarian or vegan diet. Managing a diet is complicated and a lot of different factors come into play. When you consider developing a personalized nutrition plan, therefore, here are some steps to take:
Customized nutrition plans can prove to be a challenge. Consider keeping a food journal and note how you are being impacted, not just in terms of weight and body mass, but also mood and happiness. Finding the right balance between the genes you inherit and the epigenetic influencers that alter gene expression is part of your journey through life and one you can, now that you have read all the above, to a great degree, own and control.
]]>“Osteoarthritis is the most common form of arthritis, affecting millions of people worldwide. It occurs when the protective cartilage that cushions the ends of the bones wears down over time. Although osteoarthritis can damage any joint, the disorder most commonly affects joints in your hands, knees, hips and spine. Osteoarthritis symptoms can usually be managed, although the damage to joints can’t be reversed.”
The Mayo says the only thing that those who have osteoarthritis can do is stay active, maintain a healthy weight, and try treatments to slow the progression of the disease while helping to improve pain and joint function.
Bone and Joint Canada (BJC), a not-for-profit organization that racks osteoarthritis notes that 4.6 million out of 40 million, that is more than 10% of the population, suffer from osteoarthritis. And that number is expected to grow in thirty years to 10 million.
In the United States, the Centers for Disease Control have calculated that osteoarthritis affects 32.5 million, and as in Canada, that number is expected to grow as the population of the country ages.
No country on the planet, in fact, is spared because osteoarthritis seems to come with aging. But is the Mayo Clinic right? Is osteoarthritis uncurable?
University of Adelaide researchers in Australia where one in five over the age of 45 suffer from the condition, beg to disagree with the Mayo. These researchers are working to restore Grem1 stem cells which disappear as we age coincident with cartilage thinning and degeneration.
A paper published in Nature Communications on October 31, 2023, describes the efforts of the research being done at the University’s Medical School. It describes osteoarthritis as the dysfunction of mature cartilage cells combined with an imbalance of Grem1 stem progenitor cells. Dr. Jia Ng from the Adelaide Medical School, is the lead author of the paper. In a news release from the University, he states:
“The findings of our study reimagine osteoarthritis not as a ‘wear and tear’ condition but as an active, and pharmaceutically reversible loss of critical articular cartilage stem cells.” With the discovery of the role of Grem-1 stem cells related to cartilage thinning, “are now able to explore pharmaceutical options to directly target the stem cell population that is responsible for the development of articular cartilage and progression of osteoarthritis.”
Research with stem cell injections so far has not effectively repaired osteoarthritis. A five-year clinical trial using Fibroblast Growth Factor 18 (FGF18), encoded by the FGF18 gene in humans and first discovered in 1998, has shown promise. A current Phase 3 trial using Sprifermin, a recombinant human FGF19 analog, has been encouraging.
Until recently regenerating cartilage medically has been next to impossible. Surgical efforts have been tried. These include:
A pharmaceutical solution would be a welcome change and could prove the Mayo Clinic’s pronouncement about osteoarthritis being irreversible false.
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