Podcast Host: Dr. Andrew Huberman (Stanford Associate Professor - brain development, brain plasticity, and neural regeneration and repair fields).
Oftentimes in conversation, podcast hosts/guests will reference a given study but aren't able to provide the entire context or citation link for listeners. To help underscore the impact of science podcasts, such as this one, we construct the posts to reference all studies discussed in their conversation as well as provide some more background/information on topics that we think the listeners may be interested in. If there are changes, you'd like to see to the format of these posts or any other feedback you'd like to provide - please let us know in the Discussion section below this post.
Note: In the ethos of Open Science and transparent publication, this is a living document that will undergo continuous improvement. If you have suggestions, expansions, or corrections please feel free to comment in this thread and we will adjust the document as well as award some RSC for your help.
An Australian study found that China produced one-fifth of the world's single-use plastic in 2019. This makes China the country that produces the most waste plastic, making it the world's largest generator of plastic garbage. According to the Minderoo Foundation in Perth, Australia, which released its first Plastic Waste Makers Index on Tuesday, only twenty corporations are responsible for producing half of the single-use plastic goods that are discarded each year throughout the world. And of those, one-quarter were companies with headquarters on the Chinese mainland. China has the largest population of any country in the world. According to Dominic Charles, the principal author and the director of finance and transparency at Minderoo, it should not come as a surprise that they produce the biggest quantity of waste consisting of single-use plastic in the world.
After China, the country of Indonesia, which has a total population of 250 million people, is the world's second-largest contributor to pollution caused by plastic. Each year, the nation generates a total of 3.2 million metric tons of plastic waste that is improperly managed, of which 1.29 million metric tons find their way into the ocean. On the other hand, the Philippines is regarded as the world's third-largest producer to plastic garbage, and it is estimated that the country is responsible for the production of 0.75 million metric tons of ocean plastic per year. Each year, Vietnam is responsible for the discharge of an estimated 3.1 million metric tons of waste plastic into its soil. At least ten percent of this improperly managed waste finds its way into the waterway, placing Vietnam among the top five countries contributing the most to the pollution of the world's seas with plastic
The National Action Plan on Plastic Waste Management 2021–2030 outlines the steps Sri Lanka must take in accordance with the 3Rs philosophy. The measures in this plan address every stage of the management of plastic trash, including import, processing, end-use, collection, and disposal [1].
Figure 1. Polluted countries in Plastic waste [2]
1. Heng, C. China’s plastic waste mountain the biggest in the world: study. 2021; Available from: https://www.scmp.com/news/china/science/article/3134480/chinas-plastic-waste-mountain-biggest-world-study.
2. The countries polluting the oceans the most with plastic waste. Available from: https://www.plasticethics.com/home/2019/3/17/the-countries-polluting-the-oceans-the-most-with-plastic-waste.
According to the paper, the lack of any published evidence that SARS-CoV-2 was circulating in animals before the pandemic supports the lab leak scenario. The virus appeared to have been spread by people rather than animals, according to samples of the virus found on refrigerators, worktops, and other surfaces at the Huanan market that was genetically similar to human samples. However, several experts argued that since China shut down the market and killed every animal before it could be tested, the lack of a diseased animal did not prove anything [3].
Pangolins were also sold in the Wuhan market since this meat is well-known for its delicacy and quality in China, where it was the subject of numerous papers published during the epidemic regarding matching the virus sequence with pangolins.
Also, SARS-CoV-2-related viruses in Malayan pangolins, in silico investigation of the ACE2 receptor polymorphism, and sequence similarities between the Receptor Binding Domain (RBD) of pangolin spike proteins and human Sarbecoviruses suggested pangolin as an intermediary. Later, the pangolin ACE2 receptor was found to bind SARS-CoV-2 RBD poorly [4].
DNA from raccoon dogs, which can contract SARS-CoV-2 and spread it to members of their species even if they don't exhibit any symptoms, was found in six samples. The "most logical hypothesis" is that raccoon dogs are carriers of SARS-CoV-2 and shed the virus, according to virologist Leo Poon. Where the pandemic originated cannot be determined with certainty because the study was unable to establish if the animals were indeed infected or whether the viral RNA in the swabs came from other sources [5]. If someone is working in a wet lab, there is a chance that they will accidentally release a virus, bacteria, or other biohazardous material from the lab despite using lab coats, following proper sterilization procedures, etc. Perhaps the virus leak was not intentional, but the notion that this virus was released from the lab simply seems to be true [6].
Figure 2. SARS-CoV-2 [7]
3. Sheryl Gay Stolberg, B.M.a.C.Z. The Origins of the Covid Pandemic: What We Know and Don’t Know. Available from: https://www.nytimes.com/article/covid-origin-lab-leak-china.html.
4. Frutos, R., et al., COVID-19: Time to exonerate the pangolin from the transmission of SARS-CoV-2 to humans. Infect Genet Evol, 2020. 84: p. 104493.
5. Graham, F. Daily briefing: COVID origin linked to raccoon dogs. Available from: https://www.nature.com/articles/d41586-023-00863-y.
6. Wolf, M.L.L. US COVID-origins hearing renews debate over lab-leak hypothesis. 2023; Available from: https://www.nature.com/articles/d41586-023-00701-1.
7. Jamison, D.A., et al., A comprehensive SARS-CoV-2 and COVID-19 review, Part 1: Intracellular overdrive for SARS-CoV-2 infection. European Journal of Human Genetics, 2022. 30(8): p. 889-898.
A scientist named Steve Quake, a postdoc from Stanford conducted an intriguing CRISPR experiment on newborn humans. Everyone believes that he essentially protects unborn children from HIV. This mutation also improved memory function. Chinese officials imprisoned him for breaking the law, yet his prison was opulent and featured a laboratory, so perhaps China is encouraging CRISPR experiments. Chinese military researchers are employing the method to manufacture albumin, a type of human blood protein, in young pigs. With their own cutting-edge light-induced editing devices, military researchers are improving CRISPR gene splicing. Improved cancer medication resistance is the subject of other investigations. The Chinese military is also researching using CRISPR to delete the DNA of the hepatitis-B virus.
The Chinese Academy of Sciences, specifically the Institute of Neuroscience at the Shanghai Institutes for Biological Sciences, appears to be connected to the majority of the civilian CRISPR research facilities. There are at least 50 scientists working on gene editing in dozens of labs at just these centers. And that figure is only for neuroscience. That does not include all of the Chinese CRISPR researchers working in animal or human biology. They are moving quickly through experiments with mice and monkeys. The Chinese CRISPR advances in human embryos this year, though, are more concerning. CRISPR research on human embryos is forbidden in the United States. China allegedly violates international human rights law by altering the human germ cell line, according to some reports from US officials [8].
Huntington's disease is brought on by a mutation that occurs in the gene that codes for the huntingtin protein. Because of the flaw, the components of DNA known as cytosine, adenine, and guanine (CAG) are replicated an abnormally high number of times compared to what would be expected. Because the HD gene in the majority of persons contains less than 27 CAG repeats, they do not have an increased chance of developing the condition. Also, Huntington's mutation, which causes a person to lose the ability to control their arms due to the degeneration of the brain regions responsible for controlling motor function, could also be saved using CRISPR. These writhing, and kinetic movements are a symptom of Huntington's disease. Since we knew which gene was responsible for the illness, we knew it was a hereditary condition. CRISPR technology allows you to restore a gene's normal function while simultaneously resurrecting it. [9].
The world needs to be informed by ethics committees as to what is appropriate behavior and what is not. It would be extremely advantageous to use CRISPR to treat Huntington's disease; for example, if you had a child and knew from his or her genes that one day he or she will get the disease, CRISPR would be the best course of action.
Figure 3. CRISPR Reverses Huntington’s Disease in Mice [10]
8. Gene-Edited Babies: What a Chinese Scientist Told an American Mentor. Available from: https://www.nytimes.com/2019/04/14/health/gene-editing-babies.html.
9. Vachey, G. and N. Déglon, CRISPR/Cas9-Mediated Genome Editing for Huntington's Disease. Methods Mol Biol, 2018. 1780: p. 463-481.
10. CRISPR Reverses Huntington’s Disease in Mice. Available from: https://www.genengnews.com/topics/translational-medicine/crispr-reverses-huntingtons-disease-in-mice/.
People who do salad dressing with mustard for multiple sclerosis have a huge inflammation e.g blurry vision etc. Mustard doesn’t necessarily cause whole-body inflammation, but if it is spicy mustard, it binds to capsaicin receptors. We had the receptor for anything e.g. hot and spicy. Heat is spicy and is very closely linked to pain and inflammation. Whereas pain relief is very closer to menthol and cool. Spicy things also can cause inflammation [11].
Additionally, consuming Carolina Reaper had given someone a Thunderclap headache. The meninges are the thick tissues that surround the brain, and this headache is characterized by severe inflammation of the meninges. This inflammation also led to brain damage in that guy, which was brought on by consuming a lot of spicy pepper [12].
Figure 4. Carolina Reaper causes headaches [13]
People who can tolerate stronger spices frequently have greater testosterone levels, and people with higher pain thresholds also tend to have higher testosterone levels. Additionally, testosterone levels were lower, activities were more strenuous, and eating spicy foods changed your perception of what is spicy. People's pain thresholds are also adjusted by this. Therefore, if people eat more hot pepper, they will be able to handle any kind of discomfort better [12].
Cold thermogenesis, ice baths and acute pain do what exactly exercise does. A sauna is normally a space heated to between 158 and 212 degrees Fahrenheit or 70 to 100 degrees Celsius. Dry heat is typically used in traditional Finnish saunas, and the relative humidity level is frequently between 10% and 20%. Other sauna styles have higher moisture levels. For instance, Turkish-style saunas have higher humidity levels. The average skin temperature after using a sauna is around 40° Celsius or 104° Fahrenheit. Heavy sweating happens in tandem with an increase in skin temperature. As the body tries to stay cool, the heart rate increases. During a brief visit to a sauna, it's not unusual to shed around a pint of perspiration [14].
At the University of Copenhagen, Susanna researched metabolism and brown fat. Her research on the physiology of deliberate cold and heat exposure is supporting what many cultures have instinctively known for thousands of years: altering our temperature is good for us. Her wonderfully illustrated book “Winter Swimming: The Nordic Way Towards a Healthier and Happier Life” explores cold-water traditions around the world and their remarkable health advantages [15]. Engaging with the cold has amazing mental health advantages. Pushing your comfort zone and braving the cold can boost your confidence and resilience. It increases our adaptability to modern life by releasing mood-boosting hormones and exposing us to "healthy stress." The ultimate mindfulness experience, it gets you out of your thoughts and into your body [15].
11. Olsen, N. Is Mustard Good for You? healthline; Available from: https://www.healthline.com/nutrition/is-mustard-good-for-you#nutrition.
12. Bègue, L., et al., Some like it hot: testosterone predicts laboratory eating behavior of spicy food. Physiol Behav, 2015. 139: p. 375-7.
13. Dr. Kaushik Bharati. Thunderclap Headaches. Available from: https://www.medindia.net/patientinfo/thunderclap-headaches.htm.
14. Yamini Ranchod, M. What are the benefits and risks of a sauna? 2019; Available from: https://www.medicalnewstoday.com/articles/313109.
15. Chatterjee, D.R. The New Science of Cold Exposure: Reduce Stress, Boost Immunity & Increase Resilience with Dr Susanna Søberg. 2023; Available from: https://drchatterjee.com/the-new-science-of-cold-exposure-reduce-stress-boost-immunity-increase-resilience-with-dr-susanna-soberg/.
A study shows, that brief-duration exposures to cold air do not cause any changes in serum levels of thyroid hormones or TSH. Long-term exposures to cold air, as those experienced in circumpolar climates, seem to hasten the thyroid's hormone consumption, which first shows up as low levels of free T3 and free T4. Reduced physical and mental performance could be related to this. Recently, it was discovered that mood disorders in people working in Antarctica were preceded by low serum-free T3 levels and that taking T4 supplements improved cognitive function. This raises the issue of whether or not thyroid hormones should be administered to those who live or work in extreme circumpolar environments. The hypothalamus-pituitary system (HPT is strongly activated by cold exposure, which results in an increase in thermogenesis and cold adaptation. This is coordinated by an increase in thyrotropin-releasing hormone (TRH) production, thyroid-stimulating hormone (TSH) release, and serum thyrotropin concentrations [16].
There has been researching on the effects of brief exposure to cold air on blood cortisol levels, with some inconsistent findings. The serum cortisol levels increased after a two-hour exposure to cold air (5–15º C), and the levels rose considerably more when physical stress and cold water showers were added. According to several investigations, blood cortisol levels in reaction to cold either dropped or stayed the same. Cortisol levels appear to decline more slowly when exposed to cold air (-5 to -2 degrees Celsius) in the winter than they do on a warm day in the summer. Studies have also looked at extended exposure to cold and darkness. Cortisol levels in some studies appeared to be unaffected by the wintertime, whereas others have shown increases. Two out of four test individuals had free-running and increased urine cortisol release during the arctic winter. Dopamine levels were shown to rise significantly and remain elevated for an extended period of time in participants of a study who submerged themselves to their necks in water with a temperature of 60 degrees Fahrenheit for around an hour while keeping their heads above water. Other studies describe large increases in epinephrine after only 20 seconds of exposure to water that was very cold (below 40 degrees Fahrenheit). The good news is that as you increase the frequency of your deliberate cold exposure, you will become more accustomed to being in colder temperatures at all times and will be able to start using colder temperatures with more confidence, just like you would with exercise.
One, two, or three minutes of extremely cold exposure result in a significant boost in dopamine, according to a study that was published in the European Journal of Physiology. These three substances, together known as catecholamines, are released by this exposure by 2X to 3X over baseline and further evoke epinephrine and non-epinephrine. Because some medications create such a significant increase, the increase is enormous. But the main distinction between these two treatments is that most medicines cause dopamine levels to rise above baseline. Such a medication that raises catecholamines to such a degree doesn't exist [17].
Figure 5. Cold exposure and hormones [18]
16. Zhang, Z., et al., TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold. European Thyroid Journal, 2018. 7(6): p. 279-288.
17. Blouquit, M.F., D. Gripois, and J. Roffi, Influence of cold exposure on dopamine content in rat brown adipose tissue. Horm Metab Res, 1996. 28(3): p. 122-7.
18. Chen, Z., et al., The underlying mechanisms of cold exposure-induced ischemic stroke. Science of The Total Environment, 2022. 834: p. 155514.
The five pillars of health include;
Resistance training reduces inflammation when your blood pressure rises and cytokines are released. Resistance training (RT) has been related to a lower risk of low-grade inflammatory illnesses such as cardiovascular disease and type 2 diabetes [20]. The body releases melatonin and human growth hormone to unwind and heal itself after exercise and when it cools. One of the hormones required for the body to go to sleep is melatonin. While in the sauna, other neurotransmitters and endorphins are released, reducing pain and soothing the mind [21].
19. My 5 practical pillars of health to help with the bigger picture. 2022; Available from: https://maysimpkin.com/the-5-pillars-of-health/.
20. Calle, M.C. and M.L. Fernandez, Effects of resistance training on the inflammatory response. Nutr Res Pract, 2010. 4(4): p. 259-69.
21. Harju, C. Sleep better with sauna. 2022; Available from: https://saunafromfinland.com/sauna-health-benefits/sleep-better-with-sauna/#:~:text=After%20exertion%2C%20and%20as%20the,pain%2C%20and%20calming%20the%20mind.
When we heat the surface of our body, we perceive that the entire body is becoming extremely warm, but when we measure the temperature of our core, the medial preoptic nucleus of the hypothalamus notices this change and sends signals to the core organs to decrease the core body temperature, causing the body to feel sleepy [22].
When we wake up in the morning, our body temperature has increased by one to three degrees, which further prompts a cortisol rise and the release of norepinephrine, which causes us to begin waking up. Falling asleep at night likewise necessitates a one-to-three-degree reduction in body temperature. Because of the strong correlation between body temperature and the capacity for falling asleep, staying asleep, and waking up, your entire circadian rhythm is temperature-driven. Thus, the greatest time of day for us to exercise is generally when we feel the most comfortable. If we looked at our body temperature, we would discover that when it is lowest, our grip strength is the weakest [23].
Our body temperature is also being lowered by the sauna; eventually, we won't be able to thermoregulate, and at that time, our body temperature will rise and we risk becoming hyperthermia. As a result, our body's internal temperature is trying to drop, and after we leave the house, it keeps falling rapidly [24].
People experience cold on the outside of their bodies when they take a chilly plunge. Their bodies move to produce a different form of shivering, shivering to make heat or release heat from specialized fat tissue, often known as brown fats, that is not under their skin in order to control their body temperature. Brown fats start to warm you up and further activate the thermogenic system. When we receive a similar cold shock in the future, this memory tissue produces heat. Brown fats had memories of that experience as well.
Figure 6. Thermogenesis [25]
22. Sharma., E.V.O.J.L.M.S. Physiology, Temperature Regulation. STATPEARLS 2022; Available from: https://www.ncbi.nlm.nih.gov/books/NBK507838/.
23. Harding, C., et al., Fever Incidence Is Much Lower in the Morning than the Evening: Boston and US National Triage Data. West J Emerg Med, 2020. 21(4): p. 909-917.
24. Siquier-Coll, J., et al., Heart Rate and Body Temperature Evolution in an Interval Program of Passive Heat Acclimation at High Temperatures (100 ± 2 °C) in a Sauna. Int J Environ Res Public Health, 2023. 20(3).
25. Saito, M., et al., Brown Adipose Tissue, Diet-Induced Thermogenesis, and Thermogenic Food Ingredients: From Mice to Men. 2020. 11.
In endotherms, the warm blood that circulates from the center of the body to the surface of the body normally loses heat to the surrounding environment as it gets closer to the surface. Vasoconstriction is a process that narrows the diameter of blood arteries that supply the skin. This limits the amount of blood that flows through the skin, which in turn helps the body retain heat.
Our cardiovascular system benefits greatly from the contrast of heat and cold because, to us, blood vessels like capillaries and arteries are merely tubes. However, they are actually endothelial cells, which are highly contractile. The pulsing of blood through them, which is the root cause of both systolic and diastolic blood pressure, requires them to do that. When there is no blood flow, it is under pressure, and when it is relaxed, it is under pressure. Cardiovascular and cerebrovascular illnesses are the leading causes of death worldwide. You need incredibly flexible blood capillaries, not hard ones. Going from heat to cold is essentially going from dilatation to vasoconstriction.
Vasomotion's effect on convection controls heat transport between the core and its surroundings in normothermic and moderately hypothermic conditions. Anesthesia compromises tonic vasoconstriction, which prevents core heat loss. By transferring heat from the core to the periphery, arteriovenous shunts lower the temperature difference between the two compartments. At core temperatures near 34 degrees C, thermoregulatory vasoconstriction re-divides the core and periphery, concentrating metabolic heat in the core. Thermoregulatory vasoconstriction protects core temperature under mild thermal stress by limiting cutaneous heat transport and functionally dividing the peripheral and core thermal compartments. Thus, anesthesia-induced vasomotor tone changes are a key contributor to core temperature in unwarmed or chilled people. Patients receiving intense cutaneous cooling or warming lack thermoregulatory tone to avoid core temperature fluctuations [26].
26. Kurz, A., et al., Thermoregulatory vasoconstriction and perianesthetic heat transfer. Acta Anaesthesiol Scand Suppl, 1996. 109: p. 30-3.
You can experience pleasure, happiness, and motivation thanks to dopamine. Dopamine levels in the brain spike when you feel good about what you have accomplished. However, it's likely that you begin to yearn for more of this dopamine "reward," which is brought on by a variety of pleasurable experiences, such as indulging in delectable cuisine, engaging in sex, succeeding at a game, and obtaining wealth. Dopamine surges are also caused by alcohol and many illegal drugs, which is one of the reasons why people become addicted to them. Dopamine is also involved in the regulation of body movements, emotion, learning, sleep, and memory. Dopamine deficiency can cause a person to lose motivation and excitement for things. It has been related to a few mental diseases, such as schizophrenia, psychosis, and depression.
Being over dopamine, or having too much dopamine concentrated in some areas of the brain while having insufficient dopamine in other areas, is associated with being impulsive, aggressive, and more competitive. You can experience pleasure, happiness, and motivation thanks to dopamine. Dopamine levels in the brain spike when you feel good about what you have accomplished. However, it's likely that you begin to yearn for more of this dopamine "reward," which is brought on by a variety of pleasurable experiences, such as indulging in delectable cuisine, engaging in sex, succeeding at a game, and obtaining wealth. Dopamine surges are also caused by alcohol and many illegal drugs, which is one of the reasons why people become addicted to them. Dopamine is also involved in the regulation of body movements, emotion, learning, sleep, and memory. Dopamine deficiency can cause a person to lose motivation and excitement for things. It has been related to a few mental diseases, such as schizophrenia, psychosis, and depression. Being over dopamine, or having too much dopamine concentrated in some areas of the brain while having insufficient dopamine in other areas, is associated with being impulsive, aggressive, and more competitive. Disorders including ADHD, binge eating, addiction, and gambling are among the disorders that can result from it.
The dopamine-producing nerve cells eventually deteriorate in Parkinson's disease. Dopamine aids in muscular control, therefore difficulties with muscle stiffness and mobility result. The dopamine-producing nerve cells eventually deteriorate in Parkinson's disease. Dopamine aids in muscular control, therefore difficulties with muscle stiffness and mobility result. If someone else is being lazy or putting off doing something that is more difficult than the state you are in, it will knock you down a notch more quickly. This is all based on the dynamics of the neurotransmitter dopamine. If someone is procrastinating and starts cleaning the home, which they generally don't want to do well, or if you do anything that is even more difficult than the item that you're trying to avoid, this will cause a surge in dopamine levels. It is all about dopamine; once you reach that level of dopamine deployment, you become a whole new person. A person will experience depression if their dopamine levels are artificially lowered by medication. And if you reduce it even further, you run the risk of developing the movement condition Parkinson's. If you give them back their dopamine, their mood will return, and they will also experience an increase in their ability to concentrate and their level of motivation [27].
Figure 7. Dopamine in Parkinson's [28]
27. The Science Behind Procrastination and What to Do About It. Neuropedia; Available from: https://neuropedia.com/dopamine-motivation-procrastination/.
28. Understanding Parkinson's Disease. Available from: https://www.ohsu.edu/brain-institute/understanding-parkinsons-disease.
Craig Heller's lab made a device called Cool MITT. They also did two very important tests. People were getting hot from the first one. When someone comes out of sleep, it turns out. It moves slowly. This is a problem for many important reasons that have to do with keeping people living. When a person comes out of anesthesia, their body temperature is very low, and as it rises, they wake up just like they did when they went to sleep. His lab made these heating devices that warmed people's hands or the bottoms of their feet. They found that this helped people wake up from anesthesia much more quickly. And the rate of recovery was much better, which is a very impressive finding and a reason why this isn't talked about much. Then, in the last few years, people have gotten into protocols because they have become more famous. His lab also showed that one of the reasons we fail, unlike a set of dips or chin-ups, is that we don't try hard enough. Local muscle failure is caused by work heating up the muscle in that area. The enzyme pyruvate kinase is very sensitive to heat. If your muscle gets too hot, pyruvate kinase can't work and your muscle dies [29].
It contributes to set failure. They discovered that cooling core body temperature increases work capacity. By lowering core body temperature with a device, they can double or more their work volume. Applying this approach to 50 push-ups will allow you to do 100. Muscle enzymatic reaction causes it. Palmer cooling's issue is that people say, "I'll hold ice packs," which constricts portals. Cooling requires the correct temperature. It needs the gadget to chill your palms without vasoconstriction. Cool MITT works, yet many sportsmen and football players still use other cooling methods. You need to cool down your body's heart. If you don't have cool MITT, you can just hold something cold between your hands for 20 to 30 seconds or put your hands in cold plunges [29].
Temperature and sleep, temperature and the release of these neurochemicals, and temperature and performance are all things that professional sports teams, psychiatrists, and scientists are trying to figure out right now. This is not a small variable, it's a very strong one, but it's not easy for a traditional gym to have. Maybe in the future, though. Every state will have a spot in the gym where you can do a cold plunge. It's all about being able to do more work and heal, and if your goal is to train again, it's clear that you need to be warm after training. Then you need to bring down your inflammation.
One thing that is not so secret about performance-enhancing drugs is that they can help you do more work. It's also the secret to getting a good night's sleep even when you're a little too fit. Also, if a person has more testosterone, he can work harder and heal faster.
29. Technology originally developed for soldiers.; Available from: https://www.coolmitt.com/company/about-us.
At levels that are considered to be therapeutic, an amphetamine produces a variety of psychological and cognitive effects, including euphoria, a shift in sexual desire, increased alertness, and enhanced cognitive control. It has a direct influence on the body, producing results such as enhanced reaction time, resistance to tiredness, and greater muscle strength. Like with all addictive substances, amphetamine use develops into dependence as a result of complex interactions between repeated drug exposure, biological (such as genetic and developmental characteristics), and environmental (such as social and economic factors, and drug availability) factors. It is crucial to distinguish between early substance use, intermittent and compulsive drug use, acute and chronic withdrawal, drug yearning, and relapse to drug-taking behavior in order to create reliable animal models.
Initial drug use is influenced by a variety of factors, including the subjective effects a drug produces. The mesocorticolimbic dopamine system is the primary reward pathway in the brain that amphetamine activates. Initial drug use may be motivated by both positive and negative reinforcement, i.e., the drug may be used for its capacity to heighten favorable subjective effects (positive reinforcement) or to lessen an already unpleasant state. (negative reinforcement).
Internal or external signals connected to drug delivery can develop secondary positive reinforcing effects through conditioning during ongoing drug use, and with repeated pairings, the cues can act as an incentive motivator for drug usage. Such drug-related cues are known to cause cravings in people, which may raise the likelihood that they may relapse and use drugs. The initial positive reinforcement benefits of drugs are thought to diminish with repeated use, and there will be a change from positive to negative reinforcement when drug intake is motivated by easing withdrawal symptoms rather than by eliciting bliss.
Catecholamine levels in the blood rise 1,000 times as a result of amphetamine use. There are many different types of users of Adderall. For example, 100% of those in the banking industry use the drug, whereas scientists and musicians hardly ever do [30].
Figure 8. Cocaine Addiction [30]References
30. Drug Misuse and Addiction. NIDA 2023; Available from: http://nida.nih.gov/publications/drugs-brains-behavior-science-addiction/drug-misuse-addiction.
Stanford has been excellent in allowing many faculty members to express their diverse opinions on everything from politics to covid. There is a petition supporting the right to free expression. That has been circulating on campus for some time. This is also accessible online. Some claim that there is pressure on Stanford employees, including students and administrators, to do this or that, but the university enables employees to create their own independent social media channels and communicate with the public whichever they feel is most comfortable.
Academic freedom at Stanford involves the right of faculty members to have their work evaluated according to the internal criteria of the discipline, and not, for example, on the basis of their personal or political views, or on the basis of the political consequences of their conclusions. This is one of the many ways in which academic freedom is exercised at Stanford. People are becoming more aware of the value of the distinctive knowledge that medical professionals, including psychologists, scientists, and public health authorities, hold. Since these specialists come in a variety of skill levels, it would be irresponsible to silence one group at the expense of the other. It poses a threat. Furthermore, there is no going back; there are numerous ways in which people search for direction [31].
31. Zalta, E.N., The Stanford Encyclopedia of Philosophy https://plato.stanford.edu/.
When they hear the word, people frequently mix supplements with vitamins, which causes confusion for us. However, there is an entire category of supplements, including food supplements, protein supplements, and so on. If you eat some water-soluble vitamins, you will excrete some of them. There is also a vast class of compounds that we classify as supplements but which have nothing to do with proteins, fats, carbs, vitamins, or minerals yet are known to have very potent effects. Right, while substances like ashwagandha can lower cortisol, they shouldn't be utilized for an extended period of time. However, in the short run, this can be really helpful for people, especially late in the day since late-day peaks in cortisol are terrible for humans. The National Institutes of Health now have a branch that is dedicated to these kinds of research because of this. It is commonly recognized that anxiety and depression are related.
We believe that the water that creatine puts into the muscle makes you stronger. The majority of the clinical evidence on creatine is for improving frontal brain function. It is a nootropic and is used for headaches, post-concussion recovery from surgery, and postpartum depression.
There are certain basic supplements. Originally known as athletic greens, they are now known as AG1. Now, the components of such herbal and plant-based compound combinations. You cannot take each supplement separately from others, such as magnesium for sleep or inositol for pre-diabetics; all of these conditions require exercise, which can also increase insulin sensitivity. Inositol is comparable to vitamin, but it functions in a manner that increases cells' sensitivity to insulin, which is advantageous. In type 2 diabetes, you are not overproducing insulin. In essence, this type of diabetes is an insulin overproduction disorder. Supplements were considered to be only nootropics prior to the epidemic, and people advised against using them. In addition, you need to be well-rested, eat well, and engage with others [32].
32. Dwyer, J.T., P.M. Coates, and M.J. Smith, Dietary Supplements: Regulatory Challenges and Research Resources. Nutrients, 2018. 10(1).
Scientific journals are run by people. And we know that the goal of these journals ultimately is to publish papers that are true but they also want people to read their papers, the more people read papers the more will be subscriptions, the more will and they sell.
Now, what makes a paper get published? During the pandemic, there were a need for papers that provide hope or fear or whatever it was exciting at that time. Because people were buying these journals like crazy. Also, the theyy had to pay their staff, so it’s a business. Also, money is what drives research. The more money you have, the more margin for error you can have in terms of people in your labs like if you only have a million-dollar year operating budget it’s a business. You can have two to three really good people. If you had a giant budget you can have 20 people.
When someone gets into the lab and realizes that the head of this lab has a hypothesis, that is really exciting to them, Actually this is not exciting for them, but they like the idea because it would allow them to renew their ffunding. Money is involved. Then researcherstartst experiments and shows the PI, the experiments that works and don’t show them the experiments that don’t work. Also, people had threw out data that didn’t fit their hypothesis and labeled it as not good [33].
33. Smith, R., The highly profitable but unethical business of publishing medical research. J R Soc Med, 2006. 99(9): p. 452-6.
Alzheimer's disease is the type of dementia that affects most people. It is a gradual condition that begins with a slight loss of memory and may eventually lead to a loss of capacity to carry on a conversation and respond to one's surroundings. Alzheimer's disease affects various regions of the brain, including those that are responsible for cognition, memory, and language. It has the potential to severely impair a person's capacity to carry out their regular activities.
The theory of Alzheimer's that is still widely accepted holds that the buildup of what are known as plaques and tangles, which can be seen under a microscope and have always been thought of as a signature of neurodegeneration that can be seen with the naked eye, causes Alzheimer's and dementia. And that's how people have determined whether a treatmt was effective or not. Whether or not it could lessen these plaques and tangles, which occasionally occur in human and mouse tissue.
To be clear, both in the brains of Alzheimer's patients and mice with mutations, plaques, and tangles do build. As a result, they serve as somewhat useful early models for Alzheimer's disease; nonetheless, research on the disease has been ongoing for more than a decade. Essentially, there was data fraud, commonly known as fudging of data. When someone essentially claimed that a specific protein plaque or tangle had a label that implied something that it didn't. And over a long period of time, this has led to a whole range of theories regarding which medications could be helpful in the treatment of Alzheimer's.
It's somewhat perplexing how the field has continued down this route for so long without seriously examining any other possibilities. Why no one suggested that we go back and evaluate the assumption on which all of this and some of that were based [34].
.
Figure 9. Plaques and tangles [34]
34. Abbott, A., Conquering Alzheimer’s: a look at the therapies of the future. Nature, 2023.
The majority of the cholesterol in your body is made up of LDL cholesterol, also known as "bad" cholesterol. LDL stands for low-density lipoprotein cholesterol. Your risk of developing cardiovascular disease and having a stroke is increased when your LDL cholesterol level is high. A high level of LDL can be brought on by a variety of factors. Meats such as cattle, hog, and lamb, as well as processed meats such as sausage, are considered to be "red meat."dairy products that are high in fat, such as cream, full milk, and butter. Baked products and desserts.
If you have a high level of low-density lipoprotein (LDL) cholesterol, you should try to make some adjustments to your day-to-day routines. These adjustments should include decreasing the amount of total and saturated fat in your diet, decreasing your weight (if you are overweight or obese), receiving regular cardiovascular activity, and making adjustments to your diet.
However, there is abundant proof that trans fats and saturated fats raise the risk of cardiovascular disease. The idea that dietary cholesterol is atherogenic may have been influenced by the fact that it is frequently found in diets that are high in saturated fatty acids. Eggs, on the other hand, are less expensive, packed with nutrients, low in saturated fatty acids, and high in protein and minerals. A range of vibrantly colored vegetables and fruits can be included in the healthy eating pattern together with nutrient-dense, calorie-controlled meals that have balanced nutrients [35].
Figure 10. Fatty acid and Cardiovascular disorder [36]
35. Soliman, G.A., Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease. Nutrients, 2018. 10(6).
36. Astrup, A., et al., Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 2020. 76(7): p. 844-857.
Additionally, scientists themselves now have the opportunity to profit financially, with some of us making six-figure salaries via royalties, stock options, or our roles as biotech company founders. As a result, we find ourselves in a very confusing time. Society simultaneously depends on us and has a growing mistrust of us and our intentions. According to one opinion, this mistrust is caused by a hidden conflict of interest that we have. We need funding for our study even as we portray science as a universally beneficial endeavor. The greatest researchers are becoming more and more famous and wealthy, and these attractants are strong motivators to further research and careers. We have also grown to be a part of the "capitalistic machinery," which is nevertheless criticized harshly, as a result of government policies. The innocent "gentlemen academics" of the previous century are a thing of the past. In extreme situations, it might even be justified to characterize some scientists' actions as "dishonest" and "hypocritical."
When a person is on their way to a university and they glance at the names that are written on the university buildings, they realize that these people are not being honored because they are outstanding. All of this was made possible by the generous donations of many people. The university is all business [37].
37. Resnik, D.B., Science, and money: problems and solutions. J Microbiol Biol Educ, 2014. 15(2): p. 159-61.
Any of the so-called mind-expanding substances that can create altered states of perception and thought often with the heightened awareness of sensory input but with less control over what is being experienced is referred to as psychedelic drugs. They are also known as psychotomimetic medications or hallucinogens. also see hallucinogenss.
One of the most prominent psychedelics, D-lysergic acid diethylamide (LSD-25), was produced in 1938 by a Swiss chemist at Sandoz Laboratories. LSD was hundreds or thousands of times stronger than mescaline, psilocin, and psilocybin. LSD may increase heart rate, however, it does not directly cause death. Psychoses, memory loss, and abstract thought can result from prolonged exposure. Psychedelic medicines may help treat psychotherapy, alcoholism, and mental illness, but their usefulness is unknown. These and other popular mood-altering drugs appear to work by mimicking or replacing neurotransmitters, but their exact mechanisms are unknown. Schizophrenia, OCD, and depression are associated with serowithnin abnormalities. LSD resembles serotonin molecularly. LSD use does not cause hallucinations, psychosis, or schizophrenic episodes, according to research [38].
In the US, psychedelics are still extensively utilized. Utilizing psychedelics is frequently justified by curiosity, spiritual encounters, and introspection. Males are more likely than females to consume psychedelics throughout their lifespan. The "baby boomers" and younger adults both consume psychedelics at roughly the same rates over the course of their lifetimes. However, LSD, mescaline, or peyote was more prevalent among older persons, whereas psilocybin was more prevalent among younger adults. Since the 1970s, both in the US and abroad, there has been an increase in the use of psilocybin mushrooms, most likely as a result of the spread of easy home cultivation methods, guides for finding wild mushrooms, and knowledge on the uses, effects, and methods of psilocybin mushroom usage [39].
According to studies, 3,4-Methylenedioxymethamphetamine or MDMA also a non-banned drug has the capacity to cause neurotoxicity in both humans and laboratory animals. Although numerous laboratories have studied MDMA, the mechanism underpinning MDMA-induced toxicity has not yet been fully understood. Serotonin levels in the cortex of rats and mice's terminal axons can be decreased by MDMA [40].
38. Jenkins, J.P. psychomimetic drug, psychotomimetic drug. 2023; Available from: https://www.britannica.com/science/psychedelic-drug.
39. Krebs, T.S. and P. Johansen, Over 30 million psychedelic users in the United States. F1000Res, 2013. 2: p. 98.
40. Sarkar, S. and L. Schmued, Neurotoxicity of ecstasy (MDMA): an overview. Curr Pharm Biotechnol, 2010. 11(5): p. 460-9.
Psilocybin can have long-lasting anti-depressant and anti-anxiety effects. Additionally, it seems to be beneficial in the management of despair and anxiety in those who are at the end of their lives. Additionally, for alcohol and nicotine addiction. The capacity of the brain to build new informational and emotional pathways may also be enhanced by psilocybin. Even while we're just starting to grasp the potential of psilocybin, there are also dangers. Psilocybin may make the symptoms of several illnesses worse, including schizophrenia and personality disorders. Additionally, we are aware that certain physical health issues, such as liver and heart disease, raise the possibility of adverse effects.
With normal doses of 0.2–0.4 mg/kg of psilocybin each session, body weight was the starting point for many previous psilocybin investigations. The treatments consisted of a single dose or two doses separated by an average washout period of three to four weeks. In clinical study protocols, the usual psilocybin dosage has changed to a fixed dose, frequently 25 mg, which is consistent with the previous 0.3 mg/kg weight-based dosing. The fixed 25 mg dose technique has been supported, and a recent secondary analysis of prior trial data indicated no discernible differences between it and weight-based doses of 0.29 mg/kg and 0.43 mg/kg for psychedelic effects. It is probably unnecessary to modify the dose for patients with mild to severe renal impairment because the secondary metabolite (psilocin-O-glucuronide), which is removed through kidney, is inactive [41].
Figure 11. Psilocybin structure [42]
41. MacCallum, C.A., et al., Therapeutic use of psilocybin: Practical considerations for dosing and administration. 2022. 13.
42. Psilocybin (Magic Mushrooms). Available from: https://www.drugscience.org.uk/drug-information/psilocybin/.
Consuming the appropriate amount of water assists your body to eliminate waste through means such as sweating, urinating, and defecating. According to the National Kidney Foundation, drinking water helps your kidneys remove waste from your blood, maintains the openness of the blood capillaries that travel to your kidneys, and filters waste products out of your body.
It has been discovered that drinking more water can boost mood, energy levels, and attention, particularly in school-aged children and the elderly. This, in turn, can have a good impact on cognitive and physical function [43]. Also men should drink approximately 15.5 cups (3.7 liters) of fluids each day, while women should drink approximately 11.5 cups (2.7 liters) of fluids each day. These guidelines refer to fluids obtained from food as well as water and other beverages. Food typically contributes about 20% of one's daily fluid intake, with the remaining 80% coming from beverages [44].
43. Dr. Osman Shabir, P. Levels of Hydration and Cognitive Function. Available from: https://www.news-medical.net/health/Levels-of-Hydration-and-CognitiveFunction.aspx#:~:text=Studies%20have%20shown%20that%20increasing,school%20children%20and%20the%20elderly.
44. Staff, M.C. Water: How much should you drink every day? ; Available from: https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/water/art-20044256#:~:text=About%2015.5%20cups%20(3.7%20liters,fluids%20a%20day%20for%20women.
Glucagon-like peptide 1 (GLP-1) is a peptide hormone with 30 amino acids that are created in the intestinal epithelial endocrine L-cells by the differential processing of proglucagon, a gene that is expressed in these cells. GLP-1 is responsible for regulating blood sugar levels. A guy in South America discovered Glucagon-like peptide-1 or glp-1 by isolating blood from some animal, he then puts it into other animals and realizes it suppresses appetite. The enteroendocrine L cells generate the insulinotropic peptide GLP-1. Similar to GIP, an incretin hormone called GLP-1 is quickly released in response to a carbohydrate meal and stimulates the release of both insulin and glucose-dependent insulin [45].
The primary functions of GLP-1 are to increase the amount of insulin that is secreted (that is, to perform the function of an incretin hormone) and to decrease the amount of glucagon that is secreted, which helps to control how much glucose is released after meals. Thus, GLP-1 medication enhances fullness and satisfaction while decreasing food intake, desire, and hunger in humans, ultimately leading to weight loss [46].
Figure 12. Glucagon-like peptide-1 [47]
45. Shim, J. and R. Yu, Chapter 7 - Gut Hormones in Pregnancy and Lactation, in Maternal-Fetal and Neonatal Endocrinology, C.S. Kovacs and C.L. Deal, Editors. 2020, Academic Press. p. 91-99.
46. Shah, M. and A. Vella, Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord, 2014. 15(3): p. 181-7.
47. Fuselier, T., et al., Efficacy of glucagon-like peptide-1 and estrogen dual agonist in pancreatic islets protection and pre-clinical models of insulin-deficient diabetes. Cell Reports Medicine, 2022. 3(4): p. 100598.
It is possible to decrease body fat by stimulating the hypothalamus with glp-1, which then causes the hypothalamus to send signals to numerous adipose tissues.
When we look at certain persons who move around, we see that they make movements. Non-Exercise Activity Thermogenesis (NEAT) refers to the portion of daily energy expenditure produced by spontaneous physical activity as opposed to exercise. NEAT levels can differ by up to 2000 kcal per day between those who are remaining at rest [48]. Simply bouncing on one's heal boosts one's resting glucose and one's sensitivity to insulin. However, they are still moving their soleus, albeit slightly more slowly. It appears that they simulate walking sufficiently throughout the day in order to experience these advantages. Based on research on animals, we can infer that the body's most metabolically expensive tissue is receiving signals to conserve or catabolize itself. If you are in a calorie deficit, resistance training is recommended for anyone looking to lose weight [49].
if you consume fewer carbohydrates. You will burn a higher percentage of the calories you consume as fat, but if you consume more fat, you will burn a higher percentage of the calories you consume as fat. You may not necessarily be shedding fat reserves.
48. Christian von Loeffelholz, M.a.A.L.B., MD., Non-Exercise Activity Thermogenesis in Human Energy Homeostasis. NIH, 2022.
49. Bird, S.R. and J.A. Hawley, Update on the effects of physical activity on insulin sensitivity in humans. BMJ Open Sport Exerc Med, 2016. 2(1): p. e000143
Hu quoted a nutritionist as saying that the Mediterranean diet emphasizes consuming fruit, vegetables, whole grains, nuts, legumes, fish, and a lot of olive oil. In addition to plant-based foods and minimal alcohol use, this dietary pattern "emphasizes healthy fats, especially monounsaturated fat," he noted. The second is referred to as the healthy plant-based diet, which likewise emphasizes consuming more plant items but deducts points for any consumption of alcohol and all animal products. He added that the eating regimen opposes unhealthy plant-based foods like potato goods and noted that it even discourages somewhat healthy options like fish and some dairy items. He said, "So you can imagine that people who eat a lot of animal products or highly processed carbohydrate foods would be at the lower end of this score, and vegetarians are probably on the higher end of this diet score."
According to the Dietary Guidelines for Americans, 45% to 65% of daily calories should come from carbs. Therefore, if you consume 2,000 calories per day, 900 to 1,300 of those calories should come from carbohydrates. That equates to 225 to 325 grams of carbohydrates each day [50]. Additionally, a diet strong in carbohydrates will inhibit the oxidation of fat, whereas a diet low in carbohydrates will promote the rapid oxidation of fat. Consuming carbohydrates in the days leading up to exercise will increase insulin levels, which will then reduce fat oxidation by roughly 35%(5) [51].
Beef, lamb, pork, chicken, fish, bone broth, and various organ types of meat (such as kidneys, liver, and intestines) are all staples of a diet composed solely of meat for a true carnivore. Eggs, butter, hard cheese, and heavy whipping cream are all examples of dairy products, even though some purists don't allow any dairy products at all. Pink Himalayan sea salt, Coffee with no milk or sugar, Water, All other foods, including fruits, vegetables, nuts, seeds, and grains, as well as alcoholic beverages, any beverage other than water and black coffee, and any and all types of seasonings are off limits for anyone following this diet [52].
50. Staff, M.C. Carbohydrates: How carbs fit into a healthy diet. Available from: https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/carbohydrates/art-20045705#:~:text=How%20many%20carbohydrates%20do%20you,grams%20of%20carbs%20a%20day.
51. Jeukendrup, A. Fat Burning: using body fat instead of carbohydrates as fuel. Available from: https://www.sportsperformancebulletin.com/training/base-endurance-training/fat-burning-using-body-fat-instead-of-carbohydrates-as-fuel#:~:text=A%20diet%20high%20in%20carbohydrate,35%25(5)%20or%20thereabouts.
52. Nina Kolbe and L. Hochwald. What Is The Carnivore Diet? ; Available from: https://www.forbes.com/health/body/what-is-the-carnivore-diet/.
NAD or nicotinamide adenine dinucleotide is critical in energy production in all cells, vital and levels of NAD tend to go down as we age, it’s an absolute requirements for health and life. Dr. David Sinclair is working to explore NAD pathways in his laboratory by extending the life span in mice and also there is some data from yeast. There are now some clinical trials in humans, you can’t just take NAD. There are two ways to increase NAD production in the body. One is to take nicotinamide mononucleotide or NMN, some people just try B vitamins but NMN, which enters into the cells and then converts into NAD. Some people are more proponents of taking NR, the end product is thought to be the same, however, there’s a lot of controversy about whether or NAD or Nicotinamide riboside or NR is better. Some people are giving NAD infusion. This is more expensive. After Dr. David explains about NMN, a lot of people started experimenting with it.
Nicotinamide riboside, often known as NR, is an extra recoverable NAD+ precursor that can be converted into NAD+ by either a two-step or a three-step pathway. The most common precursor in mammals is nicotinamide phosphoribosyltransferase (NAM), which can then be used to create nicotinamide mononucleotide (NMN) by the enzyme nicotinamide phosphoribosyltransferase that has the rate-limiting role (NAMPT).
A lot of people think if there are a lot of mouse trials and data available on the topic why not someone tries it on himself? When it comes to longevity nobody wants to be in the control group. Someone can take NMN as a powder or any form. There are people who can take both NMN and NR, then after taking these supplements person feels to be more energetic. The recommendation for taking NMN is 500mg to the gram, put under the tongue. The Route of administration of NMN includes capsules or pills, Intravenous, and electrophoretic patches are the most common routes.
There is a company called Metro International Biotech sometimes referred to as Metro Biotech. This is a company that has a trial. They are studying something similar to NMN with slight variation it is an experimental drug [53].
Figure 13. Nicotinamide mononucleotide (NMN)[54]
53. Shade, C., The Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integr Med (Encinitas), 2020. 19(1): p. 12-14.
54. Tarantini, S., et al., Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biology, 2019. 24: p. 101192.