Journal Club with Dr. Peter Attia | Effects of Light & Dark on Mental Health & Treatments for Cancer

    enJanuary 22, 2024

    Podcast Summary

    • The Importance of Light and Dark for Mental HealthGetting enough daylight and ensuring darkness at night can improve mental health and reduce symptoms of disorders. Latest cancer treatments focus on boosting the immune and autoimmune systems.

      Morning sunlight and bright light throughout the day are important for mental health, but so is darkness at night. The paper discussed expands on the importance of getting as much light in your eyes during the day and as much darkness at night as possible to reduce symptoms of mental health disorders. Additionally, Peter Atia presented a paper about novel treatments for cancer, emphasizing the role of the immune and autoimmune systems in cancer treatments. This episode provided valuable information about the importance of light and dark exposure for mental health and the advancements in cancer treatments. If you're interested in improving your mental health and understanding the latest advancements in cancer treatments, be sure to listen to this episode. And don't forget to check out the sponsors, 8 Sleep and BetterHelp, for tools to help you get a great night's sleep and access professional therapy online.

    • Daytime and nighttime light exposure impact mental healthStudy of 85k people reveals daytime light helps treat SAD, nighttime's effects less understood, maintaining balance crucial for mental health

      Both daytime light exposure and nighttime dark exposure play crucial roles in mental health, as shown in a study examining data from over 85,000 people in the UK. Daytime light exposure, often achieved through bright light therapy lamps, is known to help treat Seasonal Affective Disorder (SAD). However, the impact of nighttime light exposure on mood and health is less understood. This study suggests that both daytime and nighttime light exposure have independent effects on mental health. The biological mechanisms behind this involve retinal ganglion cells in the neural retina, which respond to different types of light and send signals to the hypothalamus, the master circadian clock, to regulate day and night cycles. Overall, maintaining a healthy balance of light and dark exposure is essential for optimal mental health. For those interested, JUVA offers medical-grade red light therapy devices with clinically proven wavelengths for improving various aspects of health, including muscle recovery, skin health, and even vision. BetterHelp provides online therapy services for those seeking support for their mental health and career goals.

    • Eyes have cells that respond to light and impact moodEyes have cells called melanopsin that respond to bright and dim light, influencing mood and circadian rhythm. Sunlight, even on cloudy days, can positively impact mood.

      Our eyes have cells called melanopsin intrinsically photosensitive retinal ganglion cells, which not only help set our circadian clock but also have a direct line to mood-controlling structures in the brain, such as the habenula and the release or suppression of neurotransmitters like dopamine and serotonin. These cells respond to two types of stimuli: bright light and dim light. Bright light, like sunlight, can trigger a strong response and is correlated with elevated mood. Cloudy days, which may not seem as bright, can still provide enough photons to impact mood, as the circadian clock sums all incoming photons. The recommended exposure to sunlight is around 10 minutes in the morning and 10 minutes in the evening, with the most beneficial light coming from low solar angles, as the risk of eye damage is minimal during this time. Indoor environments, even with large windows, may not provide enough relevant wavelengths of light to trigger this response unless the sun is directly visible through the window.

    • Comparing blue and orange/red light regulates our circadian clockExposure to morning sunlight advances our clock, making us want to sleep earlier and wake up earlier, while evening sunlight delays it, making us stay up later and wake up later. This comparison helps maintain a consistent sleep-wake cycle.

      Our eyes have a unique mechanism to compare blue and orange or red light, which helps regulate our circadian clock. This mechanism is most active during low solar angle sunlight at sunrise and sunset, advancing or delaying our clock respectively. Morning sunlight pushes the clock forward, making us want to go to bed earlier and wake up earlier, while evening sunlight pulls the clock back, making us stay up later and wake up later. This comparison of blue and orange or red light helps keep our clock stable, ensuring we don't drift and maintain a consistent sleep-wake cycle. However, midday sunlight, which contains all wavelengths of light equally, doesn't have the same effect on our circadian clock, making it the "circadian dead zone." It's important to note that getting both morning and evening light is best, but if only one can be achieved, morning light is preferred. This ancient mechanism, present in all organisms from single cells to humans, allows us to naturally adjust to the rising and setting of the sun.

    • The importance of natural light and timed artificial light for mental healthExposure to natural light in the morning and artificial light designed to mimic sunrise and sunset can improve mental health. Dark exposure at night is also crucial for mental health, especially for those with certain conditions.

      Our exposure to light throughout the day and at night plays a significant role in our mental health. The retina is less sensitive to light in the morning, requiring more photons to trigger a response. However, sensitivity increases as the day goes on, and viewing sunlight at low angles in the morning and evening can help offset the negative effects of artificial light at night. Additionally, dark exposure at night, independent of daytime light exposure, is essential for mental health outcomes, particularly for those with certain mental health issues. While it's ideal to get sunlight throughout the day, using specific lights designed to mimic sunrise and sunset can be helpful if natural light isn't an option. The contrast of short and long wavelength light during sunrise and sunset is crucial and cannot be fully replicated by regular bright lights. Overall, accurately timed light exposure is vital for maintaining good mental health.

    • Exposure to natural light impacts circadian rhythms, mood, and healthNatural light exposure in the morning and evening is essential for regulating circadian rhythms, affecting alertness, mood, and overall health. Indoor lights can help trigger circadian response when sunlight is unavailable.

      Exposure to natural light, particularly in the morning and evening, plays a crucial role in regulating our circadian rhythms, affecting our alertness, mood, and overall health. The color of our eyes does not impact our sensitivity to light. Ideally, we should aim to see the sunrise and sunset every day, but if that's not possible, indoor bright lights can help trigger the melanopsin mechanism when we wake up before sunrise. In the evening, especially during winter months, it's essential to get some sunlight in our eyes to help our brains and bodies orient in time. Most people spend approximately 90% of their daytime hours indoors, and indoor environments are often not bright enough to support optimal circadian health. Dimming the lights and avoiding blue blockers in the evening can help improve our overall well-being. The complex interplay of light sensitivity, temperature, and hormone output highlights the importance of considering the broader landscape of circadian biology. A recent study published in the journal Nature Mental Health emphasizes the significance of this research area for mental health.

    • Linking daytime sunlight and nighttime darkness to better mental healthStudy of over 85,000 people shows increased daytime sunlight and decreased nighttime light linked to lower risks for depression, anxiety, PTSD, and bipolar disorder

      Optimizing daytime sunlight exposure and nighttime darkness can significantly contribute to better mental health. A recent study published in Nature Mental Health, titled "Day and Night Light Exposure are associated with psychiatric disorders," might sound alarming, but the actual findings suggest otherwise. The study, which involved over 85,000 people, showed that increased daytime sunlight exposure and decreased nighttime light exposure were linked to lower risks for various psychiatric disorders, such as major depressive disorder, generalized anxiety, PTSD, and bipolar disorder. This builds upon previous research showing the importance of outdoor light exposure for mood, sleep, and circadian rhythms. The study used wrist-worn devices to measure light exposure and found that those who received more daytime light and less nighttime light had better mental health outcomes. The researchers suggest that actively seeking daytime sunlight exposure could be a simple, non-pharmacologic means to improve mental health. While the study's methods were not perfect, it provides valuable insights into the importance of light exposure patterns for mental health.

    • The significance of day and nighttime light exposure on mental healthStudies show consistent relationship between light exposure and depression/anxiety, regardless of age, sex, ethnicity, employment, and physical activity.

      The relationship between day and nighttime light exposure and psychiatric outcomes, such as depression and anxiety, remains consistent even when accounting for factors like age, sex, ethnicity, photo period, employment, and physical activity. This suggests that the role of light exposure in mental health is significant and robust. Additionally, the speaker, Dr. Huberman, shared his personal experience with taking AG1, a vitamin mineral probiotic drink, to ensure he gets necessary vitamins, minerals, probiotics, prebiotics, adaptogens, and critical micronutrients, which support various systems within the body involved in mental health, physical health, and performance. The study mentioned in the discussion aimed to examine the association between light exposure and psychiatric outcomes using three models, with adjustments for various factors. The results showed similar outcomes across all models, indicating less dependency on those variables. However, the greatest question still remains unanswered, which is likely to be addressed as the discussion continues.

    • Nighttime light exposure increases the risk of psychiatric challengesNighttime light exposure is linked to an increased probability of experiencing worse psychiatric symptoms, including major depressive disorder, generalized anxiety disorder, and bipolar disorder.

      That nighttime light exposure is linked to an increased risk of psychiatric challenges such as major depressive disorder, generalized anxiety disorder, and bipolar disorder. The odds ratio, which measures the probability of an outcome in one group versus another, reveals that as nighttime light exposure increases, the likelihood of experiencing worse psychiatric symptoms also increases. For instance, in the case of major depressive disorder, the odds ratio shows a linear relationship between nighttime light exposure and the probability of experiencing more severe symptoms. Similarly, for generalized anxiety disorder and bipolar disorder, the odds ratio demonstrates that nighttime light exposure worsens symptoms, especially for those in the highest quartile of exposure. It's essential to note that daytime light exposure, which is generally beneficial for mental health, does not have the same effect as nighttime light exposure. For individuals with bipolar disorder, nighttime light exposure is particularly problematic, regardless of their daytime sunlight exposure.

    • Proper daytime light and controlling sleep-wake cycles crucial for mental healthExcess nighttime light worsens depression, self-harm, and psychosis symptoms, while increased daytime sunlight reduces their likelihood and severity. Proper daytime light management and sleep-wake cycle control are vital for mental health treatment, especially in hospitalized patients.

      Excessive exposure to artificial light at night worsens symptoms of depression, self-harm, and psychosis, particularly in the upper quartile of light exposure. Conversely, increased daytime light exposure, ideally from sunlight, reduces the probability and severity of these symptoms. Notably, ICU psychosis, a condition where non-psychotic individuals develop psychotic episodes in hospitals due to nighttime light exposure and lack of daytime sunlight, highlights the importance of proper daytime light and controlling sleep-wake cycles in hospitalized patients. These findings suggest that managing exposure to light, particularly at night, could be an essential aspect of mental health treatment.

    • Nighttime light exposure linked to major depressive symptomsNighttime light exposure increases major depressive symptoms by 25% in the highest quartile, while daytime light exposure reduces symptoms by 20% in the highest quartile.

      The study revealed a significant relationship between nighttime light exposure and major depressive symptoms, with a 20% increase in symptoms moving from the second to third quartile, and a 25% increase in the fourth quartile. Conversely, daytime light exposure showed a 20% reduction in major depressive disorder in the fourth quartile. The study's error bars, which vary in size, suggest that the sample size was appropriately powered and not overpowered, reducing the likelihood of picking up statistically significant but clinically irrelevant findings. The study also highlighted the importance of considering the timing of light exposure in relation to mental health conditions.

    • Understanding the impact of light on mood regulation for individuals with bipolar disorderDistinguishing between day and nighttime light exposure is crucial for individuals with bipolar disorder, as nighttime light can exacerbate symptoms and maintaining darkness for eight hours every night could be a potential treatment, while minimizing bright nighttime light exposure is essential for everyone.

      The sensitivity to light and its impact on mood regulation varies greatly among individuals, particularly for those with bipolar disorder. The study discussed highlights the importance of distinguishing between day and nighttime light exposure, as nighttime light can significantly affect mood systems, potentially exacerbating symptoms for people with bipolar disorder. Conversely, daytime light exposure may have less impact on their overall mood regulation. Therefore, maintaining darkness for eight hours every night could be considered a potential treatment for bipolar disorder. Additionally, it's crucial for everyone to minimize bright nighttime light exposure, as it can disrupt circadian rhythms. A simple way to check the lux levels in your environment is by using a free app like Light Meter.

    • Impact of artificial light on sleepReducing overall light exposure at night, especially from devices, can improve sleep quality by aligning circadian rhythm. Consider dimming lights or using red filters.

      While the light from our devices may seem extremely bright, it's important to remember that it's not as bright as natural light sources like the sun or a campfire. However, the amount of light we expose ourselves to over time, especially in the evening, can significantly impact our circadian rhythm. It's not just about avoiding blue light, but also about reducing overall light exposure at night. This can be achieved by dimming the lights or using red light bulbs or filters. Additionally, the content we consume on our devices may have a greater impact on our sleep quality than the brightness level itself. So, it's essential to be mindful of the whole picture and consider both the brightness and the context of our device use before going to bed.

    • Using tech tools wisely for health insightsWhile tech tools offer valuable health insights, they shouldn't replace common sense and natural intuition. Use them as learning aids to inform healthier habits.

      While technology like sleep trackers and continuous glucose monitors (CGMs) can provide valuable insights into our health, it's essential to remember that they are tools, not definitive indicators of our overall well-being. Overreliance on these devices can lead to false perceptions of our health and potentially even cause unnecessary stress. Instead, it's crucial to approach these tools as learning aids and use them to inform healthier habits, such as minimizing light exposure at night, avoiding alcohol and late-night snacks, and getting regular exercise. Additionally, it's important to remember that these devices may not always accurately predict performance or behavior, and serious athletes often rely on more traditional methods like heart rate and morning resting heart rate to gauge their readiness for physical activity. Ultimately, technology should be used as a supplement to, not a replacement for, our natural intuition and common sense.

    • Impact of Light on Health and Well-beingMinimize direct light exposure at night, especially from electronic devices, to maintain a healthy circadian rhythm. Get enough natural sunlight during the day to improve mood and overall health.

      The quality and quantity of light we are exposed to, especially during nighttime, significantly impacts our health and well-being. Our bodies have evolved under the natural cycle of day and night, and the mismatch between our modern indoor environments and this ancient biological need can lead to various health issues. Direct exposure to blue light, especially at night, can suppress melatonin production and disrupt our circadian rhythms. It's crucial to minimize direct light exposure at night and limit the use of electronic devices, especially before bedtime. Additionally, getting enough natural sunlight during the day, especially in the morning and late afternoon, can improve mood and overall health. The wavelength of sunlight matters, with blue and ultraviolet light being more intense during daytime and potentially harmful at night. While it may not be practical to completely eliminate all artificial light at night, making conscious efforts to reduce exposure and maintain a consistent day-night cycle can contribute to better health and well-being.

    • The complex relationship between light and healthUnderstanding the intricacies of light's effects on health requires considering individual sensitivity, reverse causality, and limitations of measurement technology.

      Our perception of the world around us through light and our response to it can have significant impacts on our health and wellbeing. The New York Times' series on animals' natural fluorescence highlights the complexity of light and its effects on various species, but the same principles apply to humans. The technology used to measure light exposure has limitations, and our sensitivity to light varies greatly among individuals. Reverse causality, or the possibility that our health condition influences our behavior, is also important to consider when interpreting observations. For instance, the association between diet soda consumption and obesity might not necessarily mean that the drink is causing the weight gain, but rather that people who are obese are choosing diet soda as a lower-calorie alternative. Understanding these complexities can help us make informed decisions about how we use technology to monitor and improve our health, and how we respond to the light around us.

    • The complex relationship between sleep disturbances and depressionDepression can disrupt sleep, but manic episodes can also lead to sleep loss. Reducing nighttime light exposure and promoting good sleep hygiene may benefit bipolar disorder treatment. Artificial sweeteners may impact metabolism and brain/gut chemistry, use with caution.

      The relationship between sleep disturbances and depression is complex and bidirectional. While depression can disrupt sleep patterns, people experiencing manic episodes may also be up for extended periods, leading to increased nighttime light exposure. This can have implications for the treatment of conditions like bipolar disorder, as reducing nighttime light exposure and promoting good sleep hygiene practices can be beneficial. Additionally, the perception of sweetness, even without calories, can stimulate appetite and potentially impact metabolism. The use of artificial sweeteners, while not definitively linked to cancer or other catastrophic outcomes, may still have effects on brain and gut chemistry. As a result, it's important to approach their use with caution and in moderation. The relationship between diet and health is multifaceted, and more research is needed to fully understand these complex interactions.

    • Light's impact on mental health goes beyond circadian rhythmsUnderstanding the complex relationship between light exposure and mental health requires considering both direct and indirect effects, including circadian rhythms and underlying behavioral factors.

      The relationship between light exposure and mental health is complex and multifaceted. While light plays a significant role in regulating our circadian rhythms and impacting our mood and productivity, it's not the only factor. Behaviors such as lack of sleep, sedentary lifestyle, and screen time can also limit light exposure and contribute to mental health issues. According to the expert, about 65-75% of the effects are likely due to light directly, but it's impossible to tease apart the exact contribution of each factor. Disruptions in circadian rhythms, especially in the context of depression, have been linked to increased risk of suicide and other psychiatric health issues. Therefore, promoting natural daylight-night rhythms and addressing underlying behavioral issues are crucial for maintaining good mental health. Additionally, morning exposure to bright light can enhance the morning cortisol spike, leading to better sleep quality and overall wellbeing.

    • The correlation between psychiatric conditions and light exposurePrioritize light exposure for potential benefits in managing psychiatric conditions, even if it only accounts for 30% of causality.

      The correlation between psychiatric conditions and light exposure, as presented in the discussed paper, shows strong signs of causality based on the Bradford Hill criteria. The dose-response effect, monotonic relationship, and biological plausibility all support the proposed direction of causality. However, it's important to note that there might still be some reverse causality involved. The key takeaway for individuals dealing with psychiatric conditions is to prioritize incorporating light exposure into their daily routines, such as taking coffee on the balcony or getting outside for a few minutes. This simple addition, even if it only accounts for 30% of the causality, could have significant benefits. The discussed paper, which is a landmark study in cancer therapy, highlights the potential of a class of drugs that, while reducing mortality by only 8-10%, offers hope for future advancements in cancer treatment.

    • The immune system's ability to recognize and eliminate foreign antigensThe immune system is a complex system that effectively detects and eliminates foreign pathogens by recognizing tiny peptides on cell surfaces through adaptive immunity, allowing it to learn and adapt to new threats.

      The immune system is a complex and remarkable system that can detect and eliminate foreign pathogens while distinguishing the self from the non-self. It works by recognizing tiny peptides, often proteins, presented on the surface of cells through a process involving antigen-presenting cells and T cells. This process, known as adaptive immunity, allows the immune system to learn and adapt to new threats, making it highly effective in most cases. However, there are exceptions, such as autoimmune conditions, where the immune system mistakenly attacks the self. Despite these exceptions, the immune system's ability to recognize and eliminate foreign antigens is a crucial aspect of maintaining health and preventing diseases, including infections and cancers. Unfortunately, cancer cells have ways of evading the immune system, making it a significant challenge in cancer treatment. Understanding the intricacies of the immune system and how it recognizes and responds to threats is essential for developing new strategies to improve immune function and combat diseases.

    • The immune system's role in combating virusesOur immune system effectively fights viruses through T cells, antibodies, and physical barriers, with past exposures shaping our defenses. Fever and inflammation are part of the response, and the thymus helps prevent autoimmune responses.

      Our immune system is incredibly effective at recognizing and combating viruses, thanks to the T cells and the production of antibodies. This ability is largely due to our past exposures to viruses, with many of them having been encountered during our development. Our bodies can destroy some viruses without mounting a significant immune response, while others trigger a stronger response that can make us feel unwell. The immune response itself, including fever and inflammation, is a crucial part of the body's defense against viruses. Additionally, the body has physical barriers, such as the skin and nasal epithelium, that help prevent viruses from entering. The thymus plays a role in teaching T cells to recognize self and attack foreign substances, preventing autoimmune responses. While cancer is a genetic disease, most mutations are acquired during life and not inherited. A few cancers, like Lynch syndrome and hereditary polyposis, are inherited and caused by mutations in genes that are passed down through the germline.

    • Cancer cells' unique traits allow them to evade natural defensesCancer cells lack response to cell cycle signaling, can metastasize, and use Warburg Effect to hide from immune system

      Cancer cells are different from normal cells in several ways that allow them to evade the body's natural defenses and continue to grow and spread. They lose the ability to respond to cell cycle signaling, which results in uncontrolled growth, and they have the capacity to metastasize, or spread to other parts of the body. The Warburg Effect, a metabolic process that cancer cells use to produce energy, may also play a role in helping them hide from the immune system by lowering the surrounding pH and attracting immune cells. These characteristics make cancer cells uniquely challenging to eradicate, and understanding them better is key to developing effective treatments.

    • Cancer cells hide from the immune systemCancer cells evade the immune system through inhibitors like CTLA4, preventing T cell responses and effective treatment for most solid organ tumors

      Cancer cells have developed ways to hide from the immune system, making it difficult for the body to recognize and attack them. This is similar to how viruses evade the immune system. Although there are contagious cancers caused by viruses, such as HPV, the direct transmission of cancer from one organism to the next is less common. The immune system recognizes antigens, or peptides, from at least 80% of solid organ tumors, but the lack of sufficient T cells to act or their inhibition prevents remission. One way the body inhibits the immune system is through checkpoint inhibitors, which include CTLA4 on T cells and another receptor on antigen-presenting cells. These inhibitors act as a brake on the immune response, allowing cancer cells to evade detection. Despite the immune system's ability to recognize cancer cells, only a few solid organ tumors, such as testicular cancer and gastric cancer, have had significant progress in treatment in the last 50 years. The majority of cancer deaths in Americans come from solid epithelial tumors, including lung, breast, prostate, colorectal, and pancreatic cancers, and most of these cancers have antigens that the immune system can recognize. However, the lack of effective T cell responses and immune system inhibition make these cancers difficult to treat.

    • Blocking CTLA-4 to reduce immune system breaksResearchers discovered CTLA-4 as an immune checkpoint and developed an anti-CTLA-4 drug, epilimab, to reduce immune system breaks, leading to significant improvements in median and overall survival for metastatic melanoma patients. This discovery also led to the discovery of PD-1 as another checkpoint and revolutionized cancer treatment.

      Our immune system has checkpoints that help regulate its response to antigens. CTLA-4 is one such checkpoint that can inhibit the immune response. Researchers initially proposed blocking CTLA-4 to unleash the immune system's potential against cancer. Previously, efforts focused on giving more fuel to the immune system using interleukin 2, but this approach was effective only in a small percentage of patients with melanoma and kidney cancer. Instead, researchers decided to take a different approach and reduce the breaks on the immune system by blocking CTLA-4. The phase three study comparing anti-CTLA-4 treatment with a placebo in patients with metastatic melanoma showed significant improvements in median and overall survival. This study led to the development of epilimab, an anti-CTLA-4 drug, and the discovery of PD-1 as another checkpoint on T cells. The Nobel Prize in Medicine or Physiology in 2018 or 2019 was awarded to the scientists who discovered CTLA-4 and PD-1 for their groundbreaking work in immunotherapy. This research represents a significant advancement in cancer treatment, offering hope to patients with limited options.

    • Exploring the Effectiveness of Anti-CTLA4 and GP100 in Advanced Melanoma TreatmentStudy investigated adding GP100 to anti-CTLA4 treatment for advanced melanoma patients, focusing on those with poor prognosis due to high M stage, CNS metastases, and high LDH levels.

      The discussion revolves around a clinical study on the use of anti-CTLA4 and GP100 in treating advanced melanoma. The study involved three groups: a placebo group receiving GP100 alone, an anti-CTLA4 group, and an anti-CTLA4 plus GP100 group. The M staging system for melanoma includes M0 (no metastases), M1A (metastases in soft tissue), M1B (metastases in the lung), M1C (metastases in internal organs), and M1D (metastases in the CNS. The higher the M stage, the poorer the prognosis. The study population consisted mainly of patients with aggressive cancers, with few M0 cases, many M1As, M1Bs, M1Cs, and a significant number of patients with CNS metastases and high LDH levels. The patients had all progressed through standard therapy and the chemo used for melanoma can be toxic with limited efficacy. The study aimed to determine if adding GP100 to anti-CTLA4 treatment would provide any benefit. The discussion also highlighted the importance of LDH levels as a strong indicator of survival and the challenges of treating melanoma due to its aggressive nature and tendency to metastasize to various parts of the body.

    • Using a failed treatment as a placebo in a new combinationIn clinical trials, a previous treatment failure may be used as a placebo in a new drug combination, increasing the chances of novel discovery.

      In some clinical trials, a treatment that failed in previous trials may be used as a placebo, but with a new drug combination. This was the case with the GP100 treatment and anti-CTLA-4 drug in a study for metastatic melanoma. The rationale behind this was the belief that the combination might work and increase the probability for novel discovery. Initially, the primary outcome of the study was to measure the best overall response rate, but it was later changed to overall survival due to its significance. The study took place over many years and had strict protocols to ensure consistency across multiple centers. A partial response in cancer therapy is defined as a 50% reduction in tumor size, and the primary focus is often on overall survival due to the dire outcomes of most cancer treatments.

    • Significant difference in overall survival between control and treatment groups in advanced melanoma patientsAnti-CTLA4 and anti-CTLA4 plus GP100 treatments showed better survival outcomes than placebo in advanced melanoma patients who had progressed on high-dose interleukin-2 therapy, with the combination therapy showing a slight edge over monotherapy.

      The study showed a significant difference in overall survival between the control group (GP100) and the two treatment groups (anti-CTLA4 and anti-CTLA4 plus GP100) in patients with advanced melanoma who had progressed on high-dose interleukin-2 therapy. The Kaplan-Meyer survival curve illustrates that the two treatment groups had better survival outcomes compared to the placebo group, with the anti-CTLA4 plus GP100 group showing a slight separation from the anti-CTLA4 group towards the end of the study. Median survival in the GP100 group was particularly low, with only one person still alive after 44 months. The study also reported no complete responders in the placebo group, while there were partial responders in both treatment groups.

    • Focusing solely on median response rates in cancer research is misleadingMeasuring overall survival, the highest bar in cancer research, is crucial despite the emphasis on median response rates and cures

      While median response rates are important in cancer research, focusing solely on them can be misleading. The discussion highlighted that measuring lesion size and drawing boundaries around them on scans is a crude way of assessing treatment progress. The median response rates for the control and treatment groups were 50% dead in 6 months and 50% dead in 10 months, respectively. This means the drugs extended median survival by 4 months. However, the overall survival for solid epithelial tumors has not changed in the past 50 years, with everyone eventually dying. The importance of overall survival, which is the highest bar in cancer research, is often overlooked as drug companies primarily focus on median survival and cures. The discussion emphasized that an extra 8-10 months of living, even if not miserable, is still significant. The observation period in the study stopped, but some patients were still alive, underscoring the importance of overall survival as the ultimate goal in cancer research.

    • Pharmaceutical industry's pricing and marketing of drugs in oncologyDespite high costs and potential limited benefits, some drugs extend survival and offer significant advancements in understanding underlying biology. However, gender disparities in drug effectiveness and financial burdens on patients require further investigation.

      The pharmaceutical industry's approach to pricing and marketing certain drugs, particularly in oncology, can be met with skepticism due to the high costs and potential limited benefits for patients. For instance, drugs that extend median survival by only a few weeks can cost tens of thousands of dollars. While insurance may cover some of these costs, patients may still bear a significant financial burden. Additionally, the quality of life during treatment and the potential debt burden on loved ones are important considerations. However, it's important to note that not all pharmaceutical developments are negative. The first approval of an anti-CTLA4 drug for melanoma, though not the most effective one, marked a significant advancement in understanding the underlying biology and paved the way for more effective treatments. It's also worth mentioning that this drug showed less effectiveness in women than men in about half of the studies, which could be due to differences in immune response. Though the reasons for this gender disparity aren't fully understood, it's an intriguing area for further research. Overall, a nuanced perspective is necessary when evaluating the pharmaceutical industry, recognizing both its challenges and its potential contributions to patient care.

    • Findings on immunotherapy for advanced melanoma reveal differences in dosing and adverse effectsImmunotherapy drugs like anti-CTLA-4 and GP100 have varying doses based on weight and significant adverse effects, including autoimmune reactions, which can be severe and require corticosteroids to manage. These reactions may correlate with response rates.

      The study on the effectiveness of immunotherapy drugs, specifically anti-CTLA-4 and GP100, in treating advanced melanoma reveals some interesting findings. First, the dosing of these drugs varies based on weight, which could explain the observed differences between men and women. Second, the adverse effects of these treatments, particularly autoimmune reactions, are significant and more common in the treatment groups. The study reported high rates of autoimmune events, such as vitiligo, colitis, and gastrointestinal issues, which can be severe and may require corticosteroids to manage. The difference in autoimmune events between the treatment groups and the placebo group is substantial. It's important to note that these adverse effects can be challenging to distinguish from the natural progression of the disease. However, the study suggests a correlation between autoimmunity and response rate to these treatments. These findings underscore the importance of careful monitoring and management of adverse effects in patients undergoing immunotherapy.

    • No difference in autoimmunity between full and low dose immunotherapy, but significant difference in response ratesEarlier detection and effective treatment are crucial for preventing cancer from spreading, while the focus on stimulating the immune system periodically for cancer prevention in older adults needs further research

      In a phase two trial, there was no difference in autoimmunity between a full dose and a low dose of an immunotherapy treatment for metastatic melanoma. However, there was a significant difference in response rates linked to autoimmunity. Over time, doctors have become better at detecting autoimmune conditions earlier, which can be devastating. A personal anecdote was shared about a friend with pancreatic cancer, an unresectable and non-survivable type. The challenge is not in safely removing the pancreas but in the cancer's progression. The location of the tumor is predictive of survival, but the bottleneck is not the surgical procedure. The focus should be on early detection and effective treatment to prevent the cancer from spreading. Regarding the immune system, there is a thought that stimulating it periodically through medication could help eliminate potential cancerous growths in older adults, but this idea requires further research.

    • Enhancing Immunity to Fight Aging and CancerRapamycin can enhance cellular immunity and potentially reduce cancer risk. Checkpoint inhibitors have shown effectiveness against certain cancers with high mutation rates, and can lead to complete cancer regression but may cause side effects.

      As we age, our immune systems weaken and make us more susceptible to various diseases, including cancer. This susceptibility may be due to the accumulation of genetic mutations over time, but it's also possible that our immune systems are getting weaker. One potential solution to this issue is to enhance cellular immunity, as evidenced by the drug rapamycin. Rapamycin, when taken the right way, can enhance vaccine response and potentially reduce the risk of cancer. However, more research is needed to determine the exact mechanisms and long-term effects of rapamycin on cancer. Another interesting point is that certain cancers, such as melanoma and kidney cancer, have a higher number of mutations and are therefore more likely to produce antigens that can be recognized as non-self by the immune system. This is why immunotherapy, particularly checkpoint inhibitors, have been most effective against these types of cancers. An example of the power of checkpoint inhibitors is the story of a man with Lynch syndrome, who had already survived colon cancer but went on to develop pancreatic cancer. Despite the grim prognosis, he was enrolled in a clinical trial for a checkpoint inhibitor and experienced a complete regression of his cancer. However, the treatment was so effective that it destroyed his pancreas, leaving him with type 1 diabetes. While this outcome was unfortunate, it highlights the potential of immunotherapy to effectively target and destroy cancer cells.

    • Engineering T cells for effective cancer treatmentImmunotherapy, specifically CAR T cell therapy, shows promise in cancer treatment but faces challenges in recognizing antigens and increasing T cell numbers. Sun exposure and hereditary factors are potential risks for melanoma, and while physical sunscreens are generally safe, some chemical sunscreens may contain immune-disrupting endocrine disruptors.

      Immunotherapy, specifically CAR T cell therapy, holds great promise for treating cancer, although it currently focuses on targeting specific mutations rather than specific tissues. The challenge lies in engineering T cells to better recognize antigens and increasing their numbers to create a strong, effective army against cancer. Another topic discussed was the potential risks for melanoma, with sun exposure being a significant factor. While physical sunscreens are generally considered safe, some chemical sunscreens may contain immune-disrupting endocrine disruptors. Other potential risks for melanoma include hereditary factors and links to other cancers such as pancreatic cancer. Overall, the ongoing research and development in immunotherapy and cancer treatment hold great hope for improving survival rates and ultimately finding a cure.

    • Understanding the role of sunburn in melanoma riskSunburn, not just sun exposure, is linked to a higher risk for melanoma, particularly during early life and through repeated incidents.

      While genetic tests can help identify individuals with a higher sensitivity to sun exposure and potential risk for melanoma, the primary cause may not be sun exposure itself, but rather sunburn. Sunburn, which can occur from excessive UV damage, is linked to a higher risk for melanoma. The time in one's life, particularly early and repeated sunburns, may also play a role. It's important to be mindful of UV index and wear appropriate sun protection to prevent sunburn. The debate over sunscreens and their potential risks is ongoing, but the benefits of avoiding sunburn outweigh any potential concerns. Additionally, exposure to light, particularly early and late in the day, may have benefits and should not be ignored. The interaction between sunlight and the immune system is a complex and important field in cancer research. During their journal club discussion, Drs. Andrew Huberman and Peter Attia explored the nuances of a recent paper on the topic, highlighting the importance of understanding the relationship between sunlight, genetics, and cancer risk.

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    Dr. Stuart McGill: Build a Strong, Pain-Proof Back

    Dr. Stuart McGill: Build a Strong, Pain-Proof Back
    In this episode, my guest is Dr. Stuart McGill, Ph.D., a distinguished professor emeritus of spine biomechanics at the University of Waterloo and a world expert on spine anatomy and physiology, back pain, and rehabilitation. We discuss the most common sources of back pain, how back pain can be assessed (including self-assessment techniques), and how to design a personalized recovery plan to reduce back pain. We discuss how to train for lifelong fitness, reduce injury risk, and protect your back and joints based on your age and personal goals. We also discuss how to prevent back pain, build core stability, and explain how “McGill’s Big 3” exercises protect and strengthen the back. Dr. McGill, who is exceptionally fit in his late 60s, describes his low-time investment, personal training routine, and the specific exercises he uses for mobility, strength, and cardiovascular fitness. We also discuss controversial issues in the back pain and rehabilitation field, including how pain originates, the biopsychosocial model of pain, and treatments such as platelet-rich plasma (PRP). This episode provides clear, actionable tools to strengthen, prevent, and remedy back pain and injury so you can be pain-free while enjoying sports, exercise, and daily activities at any age. Access the full show notes for this episode at hubermanlab.com. Watch the clip on back pain relief and spine anatomy that accompanies this episode. Demonstration of The McGill Method Thank you to our sponsors AG1: https://drinkag1.com/huberman Helix Sleep: https://helixsleep.com/huberman BetterHelp: https://betterhelp.com/huberman Waking Up: https://wakingup.com/huberman LMNT: https://drinklmnt.com/huberman Timestamps 00:00:00 Dr. Stuart McGill 00:02:33 Sponsors: Helix Sleep, BetterHelp & Waking Up 00:06:23 What Causes Back Pain?; Genetics, Dog Breed Analogy 00:12:55 Tool: Skeleton & Body Type; Spine Flexibility & Discs 00:20:25 Flexibility & Exercises; Discs & Collagen 00:25:43 Sponsor: AG1 00:27:32 Stress & Tipping Point; Athletic Tradeoffs, Triathletes 00:36:17 Back Pain, Goals & Training Program 00:45:57 Spine Hygiene, Back Pain, Powerlifting 00:53:33 Genetics & Running 00:59:34 Sponsor: LMNT 01:00:46 Rehabilitation & Reducing Volume; Injury 01:07:42 Tool: Training for Lifelong Fitness, Injury & Joints 01:17:40 Pain Types, Biopsychosocial Model of Pain 01:26:15 Coaching, Explosivity & Endurance 01:32:43 Virtual Surgery & Rest, Pain Recovery 01:41:25 Tool: McGill’s Big 3; Building Back Strength & Stability 01:46:39 Inversion Tables & Spine Deloading, Disc Bulge, Tool: Lumbar Support 01:51:09 Tool: Daily Walking; Sitting 01:55:33 Deadlift & Bone Density, Glute-Ham Raise 02:06:20 Training & Age, Osteoporosis, Tool: Deadlift Alternatives 02:16:47 Tools: Biblical Training Week; Spine Stability & McGill’s Big 3; Shrinking & Age 02:24:16 Platelet-Rich Plasma (PRP); Disc Damage 02:27:56 Tools: Biblical Training Week & Strength Exercises, Neck Strength 02:35:24 Tools: Sword Play, Distal Limb Loading, Training for Symmetry 02:42:38 Tools: Biblical Training Week, Mobility & Cardiovascular Exercises, Athletic Panel 02:49:22 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures
    Huberman Lab
    enJuly 15, 2024

    Dr. Matthew Hill: How Cannabis Impacts Health & the Potential Risks

    Dr. Matthew Hill: How Cannabis Impacts Health & the Potential Risks
    In this episode, my guest is Dr. Matthew Hill, Ph.D., a professor of cell biology and anatomy at the Hotchkiss Brain Institute at the University of Calgary and an expert on the biology of cannabis. We discuss how cannabis affects the brain to produce its psychoactive effects (feeling “high”), including altered time perception, focus, memory, appetite, and stress. We discuss how THC vs. cannabidiol (CBD) affects the brain, the effects of different routes of cannabis administration (e.g., smoking, vaping, edibles), high-potency THC, and whether cannabis is addictive. We discuss if there is a link between cannabis use and the development of psychosis, anxiety, bipolar depression, or schizophrenia.  We discuss whether CBD has clinical benefits in regulating stress, promoting sleep, and treating certain diseases. We also discuss if there are real and consistent differences in the biological effects of different cannabis strains, if cannabis impacts hormones, and the uses of cannabis for the management of pain, stress, Post-traumatic stress disorder (PTSD), anxiety, and nausea. Listeners of this episode will get an up-to-date understanding of what is currently known about how cannabis affects the brain and body, including both its potential benefits and risks. Access the full show notes for this episode at hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman Eight Sleep: https://www.eightsleep.com/huberman LMNT: https://drinklmnt.com/huberman BetterHelp: https://betterhelp.com/huberman InsideTracker: https://insidetracker.com/huberman Timestamps 00:00:00 Dr. Matthew Hill 00:00:00 Sponsors: Eight Sleep, LMNT & BetterHelp 00:07:16 Cannabis, THC, Cannabidiol (CBD), Terpenes 00:12:08 Psychoactive Effects, Cannabis “High”; Time Perception 00:16:55 Cannabis & Brain, CB1 Receptor, Endocannabinoids 00:26:19 Endocannabinoids Types: Anandamide, 2-AG 00:33:46 “Munchies”, Cannabis & Appetite 00:42:17 Sponsor: AG1 00:44:06 THC & Anandamide, Pharmacology 00:52:37 THC & CB1 Receptors, Intoxication & Appetite 00:58:57 Cannabis & Focus, Memory 01:04:09 Routes of Administration, Concentration, Cannabis Research 01:15:12 Self-Regulation, Inhalation & THC, Tolerance; THC Concentrates 01:22:25 Sponsor: InsideTracker 01:23:36 Addiction & Cannabis, Cannabis Use Disorder 01:31:30 Cannabis Legalization & Use, Edibles & ER Visits 01:36:48 Oral Consumption, Edibles, Dosing & Time Course 01:41:12 Drug Testing & Cannabis, Exercise 01:46:04 Cannabis & Hormones, Gynecomastia, Sperm Quality 01:54:37 Cannabis & Pregnancy; Selling Recreational Cannabis 02:04:07 Vaping 02:07:05 Psychosis, Anxiety & Cannabis 02:17:17 Cannabis, Psychosis, Schizophrenia & Genetics 02:30:45 Cannabis Use & Schizophrenia, Manic Bipolar, THC Potency, Nicotine 02:40:37 Schizophrenia, Cannabis Legalization 02:45:06 Cannabis Strains, Indica, Sativa, Subjective Effects & Expectancy Bias 02:57:00 CBD, Pediatric Epilepsy, Adenosine 03:07:22 Entourage Effect; Placebo Effect, CBD & Doses 03:19:12 Cannabis Health Risks, Cardiovascular Risk, Schizophrenia  03:27:08 Cyclic Vomiting Syndrome & Hot Shower 03:31:30 Cannabis Benefits: Pain, Stress, Anxiety, Post-Traumatic Stress Disorder (PTSD) 03:40:18 Cannabis & Anxiety, Anandamide & Stress Response 03:45:55 Scientific Discussion, Clarification & Advancement 03:49:47 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer
    Huberman Lab
    enJuly 08, 2024

    How to Improve Skin Health & Appearance

    How to Improve Skin Health & Appearance
    In this episode, I discuss skin health appearance and why both are important indicators of the health status of your immune system, gut microbiome, and other organ systems. I explain why sunlight is essential for skin and hormone health and how excessive sunlight can accelerate skin aging and cause certain skin cancers. I discuss the different types of sunscreens (physical, chemical, and mineral-based) and potential health concerns of the chemicals found in some (but not all) sunscreens. I also discuss the importance of getting your skin (and not just moles) checked for pre-cancerous and cancer growths, the role of nutrition and lifestyle factors that improve skin health and appearance, and how to improve your skin by reducing local and systemic inflammation and supporting your microbiome.  I explain what works to improve your skin's youthfulness and appearance, including reducing wrinkles, sagging, and pore size. I review the data on ingesting (or topically applied) collagen, vitamin C, niacinamide, hyaluronic acid, and retinol, and what is known about the use of peptides (e.g., BPC-157, copper peptides) and red and far-red light phototherapies for improving skin health and appearance. I also discuss the causes of acne, rosacea, and psoriasis and explain nutritional, skin care, and prescription-based approaches to treating these common skin conditions. This episode ought to help everyone better understand the biology of the skin and help them make the best possible decisions for their skin health, care, and appearance according to age, goals, and current skin conditions. Access the full show notes, including referenced articles, books, people mentioned, and additional resources at hubermanlab.com. Andrew's New Book Protocols: An Operating Manual for the Human Body: https://protocolsbook.com Thank you to our sponsors AG1: https://drinkag1.com/huberman Joovv: https://joovv.com/huberman BetterHelp: https://betterhelp.com/huberman  ROKA: https://roka.com/huberman  LMNT: https://drinklmnt.com/huberman  Timestamps 00:00:00 Skin Health 00:02:59 Sponsors: Joovv, BetterHelp & ROKA  00:07:18 Skin Biology, Skin Layers 00:12:40 Sun Exposure, UV Light & Skin Cancers; Sunscreen 00:19:51 Aging, Sun Exposure, Skin Cancers, Physical Barriers 00:27:24 Sunburn & Skin Cancers 00:30:09 Sponsor: AG1 00:31:58 Vitamin D, Sun Exposure & Sunscreen 00:36:50 Organic (Chemical) Sunscreen & Inorganic (Mineral-Based) Sunscreen 00:49:20 Skin Cancers, Moles, Laser Resurfacing 00:53:59 Sponsor: LMNT 00:55:34 Sun Exposure, Melanoma & Life Expectancy 01:03:13 Tool: Youthful Skin, Collagen & Vitamin C 01:12:55 Peptides, BPC-157, Copper 01:20:58 Tool: Niacinamide (Nicotinamide), Youthful Skin, Dark Spots, Hyaluronic Acid 01:26:25 Tool: Retinol (Retin-A, Tretinoin, Retinyl Esters), Youthful Skin 01:33:07 Tool: Phototherapy, Youthful Skin, Treating Skin Conditions 01:41:10 Tool: Nutrition for Skin Health, Anti-Inflammatory Diets 01:47:54 Highly Processed Foods, Advanced Glycation End Products & Skin Health 01:52:08 Tools: Reduce Inflammation: Gut Microbiome, Sleep, Alcohol, Smoking, Stress 01:58:58 Acne, Hormones & Insulin; Tool: Low Glycemic Diet, Dairy 02:07:26 Tools: Face Cleansing & Acne; Scarring & Popping Pimples 02:13:29 Tool: Treating Rosacea, Alcohol, Skin Care, Nutrition 02:18:31 Stubborn Rosacea, Over Cleansing, Pulsed Dye Laser 02:21:04 Psoriasis Treatment, Immune System & Prescriptions 02:25:24 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer
    Huberman Lab
    enJuly 01, 2024

    Dr. Gabrielle Lyon: How to Exercise & Eat for Optimal Health & Longevity

    Dr. Gabrielle Lyon: How to Exercise & Eat for Optimal Health & Longevity
    In this episode, my guest is Dr. Gabrielle Lyon, D.O., a board-certified physician who did her clinical and research training at Washington University in geriatrics and nutrition. She is also an expert in how diet and exercise impact muscle and whole-body health and longevity. Dr. Lyon is a bestselling author and public educator. We discuss how healthy skeletal muscle promotes longevity, brain health, disease prevention, ideal body composition, and the health of other organs and bodily systems. She makes specific nutritional recommendations for optimal health: what to eat, how much to eat, the timing of meals, the essential need for adequate quality protein (including animal and plant-based options), supplementation, and how our dietary requirements change with age. She explains why specific types of resistance training are essential to build and maintain muscle and overall metabolic health. She also describes how to include resistance training as part of your exercise regimen — regardless of age or sex.  She also provides specific mindset tools to encourage sustained adherence to healthy eating and exercise practices. Women and men of all ages will benefit from Dr. Lyon’s practical, evidence-based protocols to improve muscle and whole-body appearance, function, and health. Access the full show notes, including referenced articles, books, people mentioned, and additional resources at hubermanlab.com. Andrew's New Book Protocols: An Operating Manual for the Human Body: https://protocolsbook.com Thank you to our sponsors AG1: https://drinkag1.com/huberman Maui Nui Venison: https://mauinuivenison.com/huberman  Levels: https://levels.link/huberman  Helix Sleep: https://helixsleep.com/huberman InsideTracker: https://insidetracker.com/huberman  Timestamps 00:00:00 Protocols Book; Dr. Gabrielle Lyon 00:03:23 Sponsors: Maui Nui, Levels & Helix Sleep 00:07:40 Skeletal Muscle & Longevity 00:11:25 “Under-muscled”, Leucine & Muscle Health 00:15:55 Muscle Health 00:19:45 Tool: Carbohydrate Consumption & Activity, Glycogen 00:25:14 Tools: Nutrition for Healthy Skeletal Muscle, First Meal 00:31:57 Sponsor: AG1 00:33:46 Quality Protein, Animal & Plant-Based Proteins 00:37:36 Dietary Protein Recommendations, Meal Threshold 00:41:19 Muscle Health & Aging 00:46:02 Supplements & Creatine; Dietary Protein 00:50:07 Tool: Dietary Protein Recommendation; Gout & Cancer Risk 00:52:43 Effects of Dietary Protein & Exercise on Body Composition 01:03:06 Thermic Effects, Protein  01:05:02 Sponsor: InsideTracker 01:06:14 Protein & Satiety, Insulin & Glucose 01:12:04 Tool: Older Adults, Resistance Training & Dietary Protein 01:17:48 Dietary Protein, mTOR & Cancer Risk 01:21:36 Muscle Span & Aging, Sedentary Behaviors 01:24:00 Mixed Meals, Protein Quality, Fiber 01:29:21 Inactivity & Insulin Resistance, Inflammation 01:38:43 Exercise & Myokines, Brain Health & BDNF 01:44:11 Tool: Resistance Training Protocols, Hypertrophy, “High Ground” 01:52:51 High Ground Exercises; Tendon Strength; Training Duration, Blue Zones 01:58:19 Movement, Exercise & Older Adults 02:04:25 Tool: Protein Timing & Resistance Training; VO2 Max, Aging, Blood Work 02:11:13 Supplements: Creatine, Urolithin A, Whey Protein, Fish Oil, Collagen 02:20:18 Fasting, Older Adults; Tool: Meal Timing 02:25:18 Animal Proteins & Dairy; Organ Meats, Vegan; Magnesium, Zinc 02:30:59 Medications & Muscle Health 02:32:49 Obesity & GLP-1 Analogs, Ozempic, Mounjaro, Skeletal Muscle 02:40:48 Benefits of Skeletal Muscle & Aging 02:42:16 Tools: Nutrition & Resistance Training for Muscle Health 02:45:44 Mindset Tools: Standards vs. Goals; Vulnerability Points 02:52:00 Mindset Tools: Neutrality; Health & Worth 03:01:14 Zero-Cost Support, Spotify & Apple Follow & Reviews, YouTube Feedback, Social Media, Neural Network Newsletter, Protocols Book Disclaimer
    Huberman Lab
    enJune 24, 2024

    Perform with Dr. Andy Galpin: Why Muscle Matters & How to Build It

    Perform with Dr. Andy Galpin: Why Muscle Matters & How to Build It
    I'm honored to share Episode 2 of the first season of Perform with Dr. Andy Galpin. Dr. Andy Galpin is a tenured full professor at California State University, Fullerton, where he co-directs the Center for Sport Performance and leads the Biochemistry and Molecular Exercise Physiology Laboratory. Andy is both a friend and a colleague, and I'm delighted to have assisted in the creation of this podcast. I'm certain you'll both enjoy and learn from it. Season 1 features 10 episodes, airing every Wednesday for 10 weeks. Dr. Galpin will cover everything from building strength, the importance of strength for long-term health, the science of breathing, the benefits of sleep extension, genetic testing for personalized training, and nutrition for injury recovery. While we have Episode 2 of Perform with Dr. Andy Galpin here, please be sure to subscribe and follow Perform with Dr. Andy Galpin on your preferred platform. Show notes for this episode can be found at performpodcast.com. Timestamps 00:00:00 Introduction from Dr. Andrew Huberman 00:01:06 Skeletal Muscle 00:04:06 Sponsors: Absolute Rest & Momentous 00:07:20 Quantity & Quality; Organ System; Health & Performance 00:12:58 Plasticity, “Look Good, Feel Good, Play Good”; Muscle Types 00:15:46 What is Muscle?, Muscle Fibers, Tendon 00:21:37 Muscle Fiber Number, Hyperplasia, Anabolic Steroids, Age 00:24:03 Myonuclei & Adaptability 00:26:27 Muscle Fiber Types, Variable Muscle Functions 00:32:24 Fiber Type & Lifestyle Factors 00:34:54 Sponsors: David Protein & AG1 00:37:37 Age & Muscle Loss, Slow vs. Fast-Twitch Fibers; Motor Units 00:46:36 Muscle Size vs. Muscle Strength, Quantity vs. Quality 00:50:56 Investigate: Muscle Quantity, Fat-Free Mass Index (FFMI) 00:56:21 FFMI, Elite Athletes, Muscle Mass 01:00:59 Muscle Asymmetry; Too Much Muscle Possible? 01:03:49 Interpret: Muscle Mass, FFMI Calculations & Percentiles 01:09:28 Tool: Intervene - Increase Muscle Mass, 72-Hour Rule 01:15:27 Sponsors: Maui Nui & Renaissance Periodization 01:17:51 Investigate: Muscle Quality & 4 Movement Principles 01:23:34 Muscle Quality & 3 Performance Principles  01:26:42 Interpret: Muscle Speed, Age 01:32:45 Muscle Power, Vertical Jump, Broad Jump 01:36:17 Muscle Strength, Powerlifting Elite, Bench Press, Leg Press, Grip Strength 01:44:05 Increasing Strength, Improve Health & Longevity 01:46:44 Tool: Intervene - Improve Muscle Quality, 4 Training Principles, 3-to-5 Rule 01:53:56 Zero-Cost Support, YouTube, Spotify & Apple Subscribe & Reviews, Sponsors, YouTube Feedback, Social Media 01:56:10 Conclusion from Dr. Andrew Huberman Disclaimer
    Huberman Lab
    enJune 19, 2024

    Dr. Zachary Knight: The Science of Hunger & Medications to Combat Obesity

    Dr. Zachary Knight: The Science of Hunger & Medications to Combat Obesity
    In this episode, my guest is Dr. Zachary Knight, Ph.D., a professor of physiology at the University of California, San Francisco (UCSF), and Howard Hughes Medical Institute (HHMI) investigator. We discuss how the brain controls our sense of hunger, satiety, and thirst. He explains how dopamine levels impact our cravings and eating behavior (amount, food choices, etc) and how we develop and can change our food preferences and adjust how much we need to eat to feel satisfied. We discuss factors that have led to the recent rise in obesity, such as interactions between our genes and the environment and the role of processed foods and food combinations. We also discuss the new class of medications developed for the treatment of obesity and diabetes, including the GLP-1 agonists semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro). We discuss how these medications work to promote weight loss, the source of their side effects, and the newer compounds soon to overcome some of those side effects, such as muscle loss. Dr. Knight provides an exceptionally clear explanation for our sense of hunger, thirst, and food cravings that translates to practical knowledge to help listeners better understand their relationship to food, food choices, and meal size to improve their diet and overall health. For show notes, including referenced articles and additional resources, please visit hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman  BetterHelp: https://betterhelp.com/huberman Eight Sleep: https://eightsleep.com/huberman Waking Up: https://wakingup.com/huberman LMNT: https://drinklmnt.com/huberman Timestamps 00:00:00 Dr. Zachary Knight 00:02:38 Sponsors: BetterHelp, Helix Sleep & Waking Up 00:07:07 Hunger & Timescales 00:11:28 Body Fat, Leptin, Hunger 00:17:51 Leptin Resistance & Obesity 00:20:52 Hunger, Food Foraging & Feeding Behaviors, AgRP Neurons 00:30:26 Sponsor: AG1 00:32:15 Body Weight & Obesity, Genes & POMC Neurons 00:39:54 Obesity, Genetics & Environmental Factors 00:46:05 Whole Foods, Ultra-Processed Foods & Palatability 00:49:32 Increasing Whole Food Consumption, Sensory Specific Satiety & Learning 00:58:55 Calories vs. Macronutrients, Protein & Salt 01:02:23 Sponsor: LMNT 01:03:58 Challenges of Weight Loss: Hunger & Energy Expenditure 01:09:50 GLP-1 Drug Development, Semaglutide, Ozempic, Wegovy 01:19:03 GLP-1 Drugs: Muscle Loss, Appetite Reduction, Nausea 01:23:24 Pharmacologic & Physiologic Effects; GLP-1 Drugs, Additional Positive Effects 01:30:14 GLP-1-Plus Development, Tirzepatide, Mounjaro, AMG 133 01:34:49 Alpha-MSH & Pharmacology 01:40:41 Dopamine, Eating & Context 01:46:01 Dopamine & Learning, Water Content & Food 01:53:23 Salt, Water & Thirst 02:03:27 Hunger vs. Thirst 02:05:46 Dieting, Nutrition & Mindset 02:09:39 Tools: Improving Diet & Limiting Food Intake 02:14:15 Anti-Obesity Drug Development 02:17:03 Zero-Cost Support, Spotify & Apple Follow & Reviews, YouTube Feedback, Social Media, Neural Network Newsletter Disclaimer
    Huberman Lab
    enJune 17, 2024

    Perform with Dr. Andy Galpin: How & Why to Strengthen Your Heart & Cardiovascular Fitness

    Perform with Dr. Andy Galpin: How & Why to Strengthen Your Heart & Cardiovascular Fitness
    I'm honored to share the first episode of the new podcast, Perform with Dr. Andy Galpin. Dr. Andy Galpin is a tenured full professor at California State University, Fullerton, where he co-directs the Center for Sport Performance and leads the Biochemistry and Molecular Exercise Physiology Laboratory. Andy is both a friend and a colleague, and I’m delighted to have assisted in the creation of this podcast. I'm certain you'll both enjoy and learn from it. Season 1 features 10 episodes, airing every Wednesday for 10 weeks. Dr. Galpin will cover everything from building strength, the importance of strength for long-term health, the science of breathing, the benefits of sleep extension, genetic testing for personalized training, and nutrition for injury recovery. While we have Episode 1 of Perform with Dr. Andy Galpin here, please be sure to subscribe and follow Perform with Dr. Andy Galpin on your preferred platform. Show notes for this episode can be found at performpodcast.com. Timestamps 00:00:00 Introduction from Dr. Andrew Huberman 00:01:07 Heart 00:03:55 Sponsors: Vitality Blueprint & Rhone 00:07:27 Muscle Types 00:09:54 VO2 max, Health & Mortality 00:15:49 Overall Health, Cardiorespiratory Fitness & All-Cause Mortality 00:25:23 Sponsor: AG1 00:26:54 Disease, Health & Mortality 00:30:02 Cardiac Muscle & Heart 00:38:29 Cardiac Muscle vs. Skeletal Muscle, Cardiac Advantages 00:43:53 Pacemakers & Heart Rate, Vagus Nerve 00:50:35 Why Doesn’t the Heart Get Sore? 00:54:32 Heart & Exercise, Stroke Volume, Ejection Fraction, Cardiac Output 00:59:21 Heart Rate Variability 01:02:41 Sponsors: Momentous & LMNT 01:06:54 Why Do You Breathe?: Oxygen, Carbon Dioxide & Respiratory Rate 01:13:37 Respiratory Rate & Stress 01:15:08 Tool: The “Three I’s”, Investigate: Heart Rate, Respiratory Rate, VO2 Max 01:19:53 Tool: Interpretation, Resting Heart Rate & Ranges 01:23:16 Tool: Interpretation: VO2 Max & Ranges 01:30:45 Athletes & Highest VO2 Max Scores 01:35:53 Elite Athletes & Context for VO2 Max Scores 01:41:42 Tool: Intervention, VO2 Max, Varying Exercise Intensities, SAID Principle 01:48:20 Tool: Varying Exercise Intensity; Intervals & Continuous Training; Frequency 01:58:18 Zero-Cost Support, YouTube, Spotify & Apple Subscribe & Reviews, Sponsors, YouTube Feedback, Social Media 01:59:55 Conclusion from Dr. Andrew Huberman Disclaimer
    Huberman Lab
    enJune 12, 2024

    Dr. Jonathan Haidt: How Smartphones & Social Media Impact Mental Health & the Realistic Solutions

    Dr. Jonathan Haidt: How Smartphones & Social Media Impact Mental Health & the Realistic Solutions
    In this episode, my guest is Dr. Jonathan Haidt, Ph.D., professor of social psychology at New York University and bestselling author on how technology and culture impact the psychology and health of kids, teens, and adults. We discuss the dramatic rise of suicide, depression, and anxiety as a result of replacing a play-based childhood with smartphones, social media, and video games. He explains how a screen-filled childhood leads to challenges in psychological development that negatively impact learning, resilience, identity, cooperation, and conflict resolution — all of which are crucial skills for future adult relationships and career success. We also discuss how phones and social media impact boys and girls differently and the underlying neurobiological mechanisms of how smartphones alter basic brain plasticity and function.  Dr. Haidt explains his four recommendations for healthier smartphone use in kids, and we discuss how to restore childhood independence and play in the current generation.  This is an important topic for everyone, young or old, parents and teachers, students and families, to be aware of in order to understand the potential mental health toll of smartphone use and to apply tools to foster skill-building and reestablish healthy norms for our kids. For show notes, including referenced articles and additional resources, please visit hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman  Helix Sleep: https://helixsleep.com/huberman AeroPress: https://aeropress.com/huberman Joovv: https://joovv.com/huberman LMNT: https://drinklmnt.com/huberman Timestamps 00:00:00 Dr. Jonathan Haidt 00:02:01 Sponsors: Helix Sleep, AeroPress & Joovv 00:06:23 Great Rewiring of Childhood: Technology, Smartphones & Social Media 00:12:48 Mental Health Trends: Boys, Girls & Smartphones 00:16:26 Smartphone Usage, Play-Based to Phone-Based Childhood 00:20:40 The Tragedy of Losing Play-Based Childhood 00:28:13 Sponsor: AG1 00:30:02 Girls vs. Boys, Interests & Trapping Kids 00:37:31 “Effectance,” Systems & Relationships, Animals 00:41:47 Boys Sexual Development, Dopamine Reinforcement & Pornography 00:49:19 Boys, Courtship, Chivalry & Technology; Gen Z Development 00:55:24 Play & Low-Stakes Mistakes, Video Games & Social Media, Conflict Resolution 00:59:48 Sponsor: LMNT 01:01:23 Social Media, Trolls, Performance 01:06:47 Dynamic Subordination, Hierarchy, Boys 01:10:15 Girls & Perfectionism, Social Media & Performance 01:14:00 Phone-Based Childhood & Brain Development, Critical Periods 01:21:15 Puberty & Sensitive Periods, Culture & Identity 01:23:55 Brain Development & Puberty; Identity; Social Media, Learning & Reward 01:33:37 Tool: 4 Recommendations for Smartphone Use in Kids 01:41:48 Changing Childhood Norms, Policies & Legislature 01:49:13 Summer Camp, Team Sports, Religion, Music 01:54:36 Boredom, Addiction & Smartphones; Tool: “Awe Walks” 02:03:14 Casino Analogy & Ceding Childhood; Social Media Content 02:09:33 Adult Behavior; Tool: Meals & Phones 02:11:45 Regaining Childhood Independence; Tool: Family Groups & Phones 02:16:09 Screens & Future Optimism, Collective Action, KOSA Bill 02:24:52 Zero-Cost Support, Spotify & Apple Reviews, YouTube Feedback, Social Media, Neural Network Newsletter Disclaimer
    Huberman Lab
    enJune 10, 2024

    LIVE EVENT Q&A: Dr. Andrew Huberman at the Brisbane Convention & Exhibition Centre

    LIVE EVENT Q&A: Dr. Andrew Huberman at the Brisbane Convention & Exhibition Centre
    Recently I had the pleasure of hosting a live event in Brisbane, Australia. This event was part of a lecture series called The Brain Body Contract. My favorite part of the evening was the question and answer period, where I had the opportunity to answer questions from the attendees of each event. Included here is the Q&A from our event at the Brisbane Convention & Exhibition Centre. Sign up to get notified about future events: https://www.hubermanlab.com/events Thank you to our sponsors AG1: https://drinkag1.com/huberman Eight Sleep: https://eightsleep.com/huberman Resources Mentioned Huberman Lab Non-Sleep Deep Rest Protocols Huberman Lab Guest Series with Dr. Matt Walker Huberman Lab Guest Series with Dr. Paul Conti Huberman Lab Guest Series with Dr. Andy Galpin Dr. Becky Kennedy: Protocols for Excellent Parenting & Improving Relationships of All Kinds Perform with Dr. Andy Galpin Timestamps 00:00 Introduction 00:31 Sponsors: AG1 & Eight Sleep 03:48 Nicotine Discussion 07:42 ADHD Management: Tools & Medications 12:43 Sleep Deprivation & Recovery 18:54 Understanding & Addressing Burnout 22:12 Daily Nutrition & Eating Habits 24:40 Understanding Food & Neural Pathways 26:21 The Benefits of Elimination Diets 27:21 Intermittent Fasting & Personal Diet Choices 28:23 Top Health & Fitness Recommendations 30:50 The Value of Non-Sleep Deep Rest (NSDR) 33:08 Testosterone Replacement Therapy Insights 38:02 Breathing Techniques for Stress & Focus 41:46 Morning Sunlight & Circadian Rhythms 43:18 Parenting Tips for a Healthy Start 49:03 Final Thoughts & Gratitude Disclaimer
    Huberman Lab
    enJune 07, 2024

    Dr. Mary Claire Haver: How to Navigate Menopause & Perimenopause for Maximum Health & Vitality

    Dr. Mary Claire Haver: How to Navigate Menopause & Perimenopause for Maximum Health & Vitality
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    Vitamin C for Cancer Treatment with Professor Margreet Vissers

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    The battle against cancer has been ongoing for hundreds of years now. But recently, interest in using vitamin C to improve outcomes for cancer patients has been growing. And the results of these various studies look promising.

    Biochemist and medical researcher Professor Margreet Vissers joins us in this episode to explain her current research on vitamin C and how it helps the immune system fight cancer. She also talks about the other health benefits of vitamin C, as well as some of its limitations.

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    1. You will learn about vitamin C’s role in controlling tumours.
    2. Discover how humans metabolise vitamin C differently from other animals.
    3. Know how intravenous vitamin C turned around a leukaemia patient’s relapse.



    • Watch Professor Margreet Vissers' lecture on her work on vitamin C.
    • “The power of C” on University of Otago Magazine
    • Das, A. B., Kakadia, P. M., Wojcik, D., Pemberton, L., Browett, P. J., Bohlander, S. K., & Vissers, M. C. M. (2019). Clinical remission following ascorbate treatment in a case of acute myeloid leukemia with mutations in TET2 and WT1. Blood Cancer Journal, 9, 82. doi: 10.1038/s41408-019-0242-4
    • Vissers, M. C. M., & Das, A. B. (2018). Potential mechanisms of action for vitamin C in cancer: Reviewing the evidence. Frontiers in Physiology, 9, 809. doi: 10.3389/fphys.2018.00809
    • Ang, A., Pullar, J. M., Currie, M. J., & Vissers, M. C. M. (2018). Vitamin C and immune cell function in inflammation and cancer. Biochemical Society Transactions, 46, 1147–1159. doi: 10.1042/bst20180169
    • Carr, A. C., Vissers, M. C. M., & Cook, J. S. (2015). Parenteral vitamin C relieves chronic fatigue and pain in a patient with rheumatoid arthritis and mononeuritis multiplex secondary to CNS vasculitis. Case Reports in Clinical Pathology, 2(2), 57–61. doi: 10.5430/crcp.v2n2p57
    • Dachs, G. U., Munn, D. G., Carr, A. C., Vissers, M. C. M., & Robinson, B. A. (2014). Consumption of vitamin C is below recommended daily intake in many cancer patients and healthy volunteers in Christchurch. New Zealand Medical Journal, 127(1390). Retrieved from https://www.nzma.org.nz/journal
    • Carr, A. C., Vissers, M. C. M., & Cook, J. (2014). Parenteral vitamin C for palliative care of terminal cancer patients. New Zealand Medical Journal, 127(1396). Retrieved from http://www.nzma.org.nz/journal
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    • Pullar, J. M., Carr, A. C., & Vissers, M. C. M. (2013). Vitamin C supplementation and kidney stone risk. New Zealand Medical Journal, 126(1384). Retrieved from http://www.nzma.org.nz/journal
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    Episode Highlights

    [04:50] Vitamin C and White Blood Cells

    • After killing bacteria, white blood cells destroy themselves so that the toxicity doesn’t spill into tissues.
    • Vitamin C plays a role in regulating the cell death pathway.
    • Margreet observed that white blood cells low in vitamin C did not go to resolve the end of the infection.

    [07:15] How Neutrophil Extracellular Traps (NETs) Work

    • NETs are a variation of vitamin C’s mechanism.
    • Neutrophils are cells attracted to infection and eat hundreds of bacteria. They have oxidants that kill bacteria.
    • Neutrophils eject ‘niche’ or the DNA package inside them. The niche has microbicidal proteins. The niche forms ‘traps’ that localise bacteria on the site of infection.

    [13:18] Vitamin C Production in Animals

    • All animals make their vitamin C mostly in the liver; some produce the vitamin in the kidney. Animals that can make vitamin C do it on demand. They can increase production a hundred times to keep blood levels saturated.
    • Humans lost the gene to make vitamin C; thus, we are dependent on food for supply. When we are sick or infected, our body consumes vitamin C fast. If we do not replenish our vitamin C, our body levels will decline.

    [16:35] Route of Vitamin C Administration

    • Plasma vitamin C levels go up to a maximum level of 100 micromolars.
    • Kidneys filter and regulate vitamin C. Saturated tissues will not absorb any more vitamin C; the excess will be released in the urine.
    • Oral intake is suitable for day to day intake while people with severe illnesses will need infusion.
    • Vitamin C infusion results in high plasma levels for a short period. Any excess will pass, and the plasma levels will be back to normal in 8 or 9 hours.

    [22:01] Function of Vitamin C

    • The enzyme needed to produce collagen needs vitamin C; thus, the vitamin is good for the skin.
    • It plays various roles in inflammation, wound healing, controlling infection, and even brain function.
    • Vitamin C regulates gene expression.
    • Vitamin C supports the production of serotonin, as well as other hormones that regulate mood and reproduction.

    [27:48] What Vitamin C Dosages Do We Need?

    • The Ministry of Health recommends 200 milligrammes a day for wellness.
    • Foods high in vitamin C, such as kiwi fruit, capsicum, and broccoli, are recommended. But only a few people eat a good range of fresh fruit and vegetables.
    • Margreet says if the aim of vitamin C intake is to alleviate illness, it is usually not achievable through our daily diet.
    • Each condition requires a different recommended intake.

    [34:17] The Role of HIF Protein in Cancer

    • Hypoxia-inducible factor (HIF) is a transcription factor protein that switches genes on and off.
    • HIF is present in all cells at all times and responds to low levels of oxygen.
    • Under low oxygen levels, areas with poor blood vessels are provided with oxygen by generating new blood vessels.
    • Cancer cells hijack this mechanism to have their supply of blood vessels, making the cells grow more.
    • Hijacking the HIF protein also results in switching the cancer’s energy source to sugar.

    [39:06] The Role of Vitamin C in Cancer

    • The HIF proteins need to be shut off to prevent cancer from worsening.
    • Enzymes that need vitamin C can switch off HIF proteins that need to be shut down, slowing down the tumour’s growth rate.
    • Though it is tough to prove preventive action, many cancer rates have significantly decreased to half when vitamin C status is good.
    • To maintain your well-being, keep vitamin C levels at optimum levels.

    [45:07] Does Vitamin C Pose Any Risk?

    • Vitamin C’s oxidation products need to be cleared out of the body.
    • No toxic dose has been identified, provided you have good kidney function.
    • There is no actual risk of kidney stone formation and kidney injury.
    • People getting an infusion must be tested for kidney function.

    [49:10] IV vs Oral Vitamin C Administration for Cancer

    • Any amount of oral vitamin C has not shown potential to benefit solid tumours.
    • Infusion is more advantageous than oral administration because it gets vitamin C to the core of the cancer to switch HIF protein off.
    • Margreet shares the story of Anton Kuria, a previous leukaemia patient on IV vitamin C who experienced remission for two years.
    • Vitamin C restored the normal functioning of the cells and wiped out most of the cancer cells.
    • He relapsed not because he stopped vitamin C but because the cancer cells acquired new mutations.

    [59:30] How Vitamin C Contributes to Quality of Life

    • Vitamin C regulates adrenaline and boosts energy because it is key to making molecules that help energy production.
    • It also alleviates the side effects of chemotherapy.
    • Vitamin C also improves brain fog, concentration, mood, pain, nausea and fatigue.
    • It does not interfere with other cancer treatments.

    [1:06:02] Applications in the Clinical Setting

    • Vitamin C is probably not going to kill cancer, but it can control it.
    • Vitamin C gives an insight on how to manage the disease in the clinic.
    • The excellent response to vitamin C is an opportunity to make it work better with other treatments.
    • There will almost certainly be a quality of life benefit. It can alleviate the side effects of cancer and the disease itself.
    • The beneficial effects manifest, so it is worth doing.

    [1:16:56] What Needs to Be Done?

    • We need to figure out how to apply vitamin C clinically and under specific circumstances.
    • Give people the best information so that they can make the right choices.
    • With better information, clinicians can also make informed choices for the benefit of their patients.


    7 Powerful Quotes from This Episode

    ‘All of these things that cancers do to promote their survival is mediated by this response, and right at the center of this is the vitamin C off switch’.

    ‘Vitamin C is a very labile molecule, so very easily lost. And if you're not putting in more supply, then your body level is going to drop’.

    ‘If there's any wealthy people sitting out there, if you want to support this sort of research — it is absolutely essential because we're losing people left, right and center to these horrible diseases like cancer, like sepsis’.

    ‘I'm excited about this research, I really am, because it's going to save lives’.

    ‘That's why we try to do the research — because doctors have the patient's best interests at heart’.

    ‘Our clinical people, they’re at the coalface, and they're having to make life and choice decisions for their patients all the time’.

    ‘Many cancer rates significantly decreased by up to half for a number of cancers if your vitamin C status is good rather than bad’.


    About Professor Vissers

    Professor Margreet Vissers is a biochemistry academic from Waikato University and is currently the Principal Investigator and Associate Dean (Research) at the University of Otago in Christchurch, New Zealand. She has written and published journals and books about how vitamin C can help cure and prevent cancer.

    If you want to learn more about oxidative medicine from Professor Vissers, you may contact her at margreet.vissers@otago.ac.nz.


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    To pushing the limits,



    Welcome to Pushing the Limits, the show that helps you reach your full potential with your host Lisa Tamati, brought to you by lisatamati.com.


    Lisa Tamati: Welcome everybody back to Pushing The Limits. This week I have Professor Margreet Vissers with me who is sitting in Christchurch. Now Professor Vissers, I'm just super excited. I'm a little bit nervous and excited to be talking to you today. Margreet, so can you tell us firstly, what your background is? Give us a little bit of context. You have a PhD done, free radical research and oxidant research from what I understand, and now you are very much deep into vitamin C research. Can you give us a bit of your background first?

    Professor Margreet Vissers: Okay, yeah, yeah. Morena, Lisa. it's lovely to chat with you. I've trained originally as a biochemist. So when I was at Waikato University, I had this lecturer who kind of got me excited about biochemistry, it was a new thing at that time. And so I continued, that's become my passion, just understanding how things work in our bodies. So, I became interested in white blood cells. When I was doing my PhD, my PhD was on white blood cells that fight infections. 

    And something we know about white blood cells is that they need a lot of vitamin C. They have a lot of vitamin C and we never knew why. So, all our white blood cells have a lot of vitamin C. So, there was always this question as to why do they need that. And that kind of percolated away in the background while we were researching other things. And then one day, these experiments where you added vitamin C and to kind of knock out any oxidant fixed because it's a well-known antioxidant. And it has this remarkable effects on the cells that I was working with which was the complete opposite of what I had expected. And when this happens in the lab, you usually think, ‘Are my samples in the wrong way’? I've got the best hunches. 

    So instead of acting as an antioxidant, it seemed to be enabling cell death. And which was like really paradoxical. And, and so we did it again. And you know, same thing happened again. And not only was it a really strong effect, which antioxidants usually are, they're usually more graded. It was also an on-off event. So, if there was no vitamin C, it didn't happen. And if there was just a bit, it happened really well. 

    And so we're looking for another activity. This is not an antioxidant, actually. We're looking for a different kind of function. And so this was in about 2001. And at the same timeso that wasn't work with white blood cells, that I was doing that, and that was a cancer work. 

    And so, around about the same time, there was a discovery made overseas about this new class of enzymes that regulates hypoxia, the hypoxic responses, survival response, and that those enzymes require vitamin C to function. And I realized that what I’dbecause I've been gone on thinking, ‘If it causes cells to die. Maybe it does this in white blood cells because that's the one thing that we need our white blood cells to do’. Apart from kill bacteria, we then need them to die themselves off.

    Lisa: Yes.

    Prof. Margreet: And to die tidally. Without, we need them to devastate the tissues around. It's a very controlled process. And I thought, ‘Maybe that's what vitamin C is doing in the cell. That it’s regulating the cell death pathway’. And so I did these experiments with white blood cells that didn't have any vitamin C and essentially showed that exactly to be true. That if white blood cells were low in vitamin C, they did not go on to resolve this what would be the end of an infection. So…

    Lisa: So they wouldn't end up...

    Prof. Margreet: They would end up. So, normally you have your white blood cells that kill the bacteria. They then destroy themselves in that process, because it's an endpoint reaction, and we need to clear those white cells. And so you need to clear them. They're full of all kinds of toxic things. You need to clear them in a way that doesn't spill all that toxicity into the tissues. Other white blood cells come along and eat those white blood cells. So theyit's like wrapping your garbage. 

    So that if they didn't have vitamin C, that didn't happen. So, the other white blood cells would come in, but they basically couldn't see those other cells around them. And so they get the cell death and cell leakage. And I thought, ‘Ah, so scary. There's all kinds of things that happen when you're low in vitamin C’. And so this, and then I realized also that actually, this factor that controls this process, is also the thing that allows cancer cells to grow. And, and so this is a normal response in ourselves, and we need it for survival. You know, I swear, every day survival is dependent on this process working well. 

    Cancer cells hijack the system to enable them to survive. And so, that means that it allows them to grow outside of an oxygen supply to make new blood vessels, to create a different energy source, so they can live on sugar instead of a more complex energy. It enables them to evade chemotherapy and enables them to undergo metastasis. All of these things that cancers do to promote their survival is mediated by this response, and right at the center of this is vitamin C off switch.

    Lisa: Code that. So can we just pick up just a tad there. So, I've listened to a lecture by Dr. Berry Fowler that we mentioned earlier, talking about NETs, Neutrophil Extracellular Traps. So, is that what we're talking about here? So the neutrophils are coming along, eating the bugs? 

    Prof. Margreet: That's a variation on that thing. So yes, neutrophils are astounding cells. And so, their function is to kill bacteria. The primary way that they do thatso they are attracted to any place where there's an infection. The primary way that they act is to first of all, eat the bacterium so that one neutrophil can swallow hundreds of bacteria. And then inside that pocket inside themselves, they pour onto those bugs within minutes, toxic enzymes and oxidants, including chlorine bleach that kills the bug. 

    So, what they also do is they can inject from themselves, from the cell, they can inject their DNA. They can kind of melt the nucleus inside the cell with the DNA package. They can unpackage that, and then they can inject that from the cells, and that's what we call a niche. And that niche is coated with some of those microbicidal proteins. DNA is, as you might have seen pictures of it, that's a really sticky line…

    Lisa: Yes, like egg white.

    Prof. Margreet: …molecule. And so that can basically go a long way, and it doesn't degrade very easily. So, your body doesn't have a lot of DNAs floating around that can chew up DNA. So, these traps can sit there and they trap the back. They literally physically trap the bacteria onto the site of the infection. So, that can basically help localize that infection so that it's not traveling to other parts of the body.

    Lisa: Does it even cause things like, if this infection was, say in the lungs, you'd get whiteout and that's the whiteout. Actually, what you're saying…

    Prof. Margreeet: The whiteout in the lungs is either lots of neutrophils, just a lot of neutrophils, or a lot of fluid. Where we're seeing new neutrophil NETs, or their traps, and in the lungs as in COVID patients. So, there are these peculiar things going on in the lungs of COVID patients, where they're seeing quite localized and didn't wash out. So, not the kind of diffused whiteout that you see in a pneumonia, someone with respiratory distress, but very localized pockets. And we think that looking like, as all this information’s unfolding pretty much as we speak. It looks like neutrophil NETs central to that process that enhances that cytokine storm in COVID patients who end up with severe disease. So currently, the literature is jumping with…

    Lisa: With vitamin C, and what would be helpful or not in the COVID scenario? No one's know it yet?

    Prof. Margreet: No, it's not jumping with vitamin C and COVID. The Chinese, interestingly, published protocols for how to handle COVID patients. And they have they recommend, as soon as the patient comes into, into the hospital, should be giving them intravenous vitamin Cl to keep them out of ICU. And, or as soon as they get into ICU, to prevent them progressing. They've got very careful protocols about… Actually, their protocols say that helps. This is definitely a helpful step. We haven't taken that up, the rest of the world, despite some people advocating for it.

    Lisa: So why would that be? Is it because… or we don't want to go into that? 

    Prof. Margreet: That's a very good question. I've struggled with answering that question we come up against it all the time. That people will give vitamin D before they get vitamin C. Even though people have beenwe've shown that patients who are really ill, have low vitamin C, unless you give them more. 

    Lisa: So, the sicker we get, the more vitamin Cand I've seen some of your lectures where you've shown graphs of people coming into hospital, and then the levels of plasma vitamin C are very low compared to the generally well, population. And I know from other research that I've done too, in this case, like my father's with sepsis. He would have been probably at the level of scurvy. I can't show that because they couldn't explore it, and would have been needing massive dosages of vitamin C. So the sicker we are… so, this is what's funny people is that animals produce their own vitamin C. The goat is the king of vitamin C making. I believe from Linus Pauling’s work. And the goat can produce up to 70 grams a day of vitamin C. We don't

    Prof. Margreet: So yes. All animals bear a few, make their own vitamin C in the liver, and some animals in the kidneys. There's a few miscellaneous animals, including all primates, of which we have oneso, chimpanzees and gorillas and monkeys in us, who way back, lost the gene to make it. And so we're dependent on eating it. Guinea pigs similar, and fruit bats are the other most common species. 

    So, we're dependent on eating it for our supply. Now, all animals that make their own, make it according to demand. So, they keep their blood level saturated, no matter what. So if they get sick, and their body starting to consume more, their liver makes more. And so they just keep themselves saturated. And they can increase production up to 100 times, in order to maintain that level. So we can't do that. So we're totally dependent on what we put in our mouth. 

    And so, once we get sick, and our bodies consuming more, if we're not compensating for that, then our body levels will decline. So it's totally about supply and demand. So, when you're normally well, your body's just ticking over a little bit. A good diet is good to keep you optimal under those circumstances. You get a cold, you're consuming a little bit more. Now most people, when they get a cold, they run off and get some citrus or something because that's what that feels like eating them naturally. If you get a flu, that demand goes out even more. If you get pneumonia, it goes up even more. And so the sicker you are, the more vitamin C your body's consuming. Not all. Some illnesses are more oxidative than others. 

    But any infection, like the minute you ramp that up, and that can be like a local infection. It can be burn infection. So it doesn't have to be like a whole body infection. We just recently did thishave been doing a study with people with chronic wounds like leg ulcers, and most of those people have low vitamin C status. And that won't be helping the wound. So as soon as your body has a demand to put on it, vitamin C is a very labile molecule, so very easily lost. And if you're not putting in more supply, then your body level is going to drop.

    Lisa: And then we're also limited out with the oral administration of vitamin C. Our bowels can only tolerate, before we get diarrhea, or something like that. So if our power intake to the levels that we might need if we were severely ill, we wouldn't get upbecause our plasma levels only go to 100 micromolar from what I understand. We can't actually get higher than that from all dosing.

    Prof. Margreet: Oh well, only a little bit transiently. So, if you wouldn't take a one gram tablet, your plasma level would go up to above 100 for a little while. So maybe that might get up to 150. But your kidneys will clear that. And so I always kind of give the analogy of a dry sponge. So if you imagine that you're pouring water on a dry sponge, that your body is... Your blood is only the delivery mechanism, so vitamin C is going to get from your blood into the cells. If your blood levels are low, your tissue levels will be low. So that's a dry sponge. 

    So if you pour more vitamin C onto there, it will go into circulation. But as soon as it's in the blood supply, it will be sucked out into those tissues. So your kidneys will never see that above 100 micromolar. Once your tissues are saturated, so the whole sponges which you might, if you pour more on and then you touch, and then your blood supply goes up over 100, stays over 100 because your tissues are not taking up any more than they need. Then there's a filter in the kidneys that regulates that all vitamin C passes out, and then it's like, ‘How much is in the bloodstream’? ‘Do I need any more’? ‘And then I'll take it back up’. So it gets taken back up or not. And if the body's got enough, then no more be taken up and end up down the toilet which is fine.

    Lisa: Yes, it's not going to hurt you. But if so, then intravenous vitamin C has a different mechanism though, isn't it? We can get the micromotors up quite high.

    Prof. Margreet: Intravenous delivery is such fast, express delivery. And so it's to be whatit can do two things. What we think, it can be useful in under two circumstances. So normally for your day to day health, oral intake, this is ample. If you are reallya lot people in ICU, or who are people with severe pneumonia who are turning over vitamin C at a great rate, it's really hard to get like you might need to give those people seven or eight grams of vitamin C a day, in order to restore, get their plasma level sit close to normal. So it's hard to give that amount of oral intake to people who are that sick. 

    And so under those circumstances, the easiest thing to do is just to inject that, and that's what we call infusion. So then you bypass the gut, you can just infuse it straight into the circulation. And the rate of infusion determines that that plasma level will be very high for a very short time, then it will go out into the body where it needs to be. And any excess will pass out. And then urine. So after about eight or nine hours, you're back to normal. But your tissues, your sponges.

    Lisa: Yes, so that they are in what they need. The vitamin C that's actually in the cell will stay around longer than, won't it? And do its actual job, if it's in the mix.

    Prof. Margreet: It's doing its job, that’s right. So those cells that had become depleted and now have a function restored. And what we've discovered is, it's not just one function anymore. So in the last 10 years, vitamin C has been shown to be involved in supporting... So initially thereeveryone will know about... Walk into any chemist and you'll see vitamin C creams for sale, cosmetics. Rub it on your face, or whatever. But because we all believe that vitamin C is good for our skin. And it is good for your skin, actually. It's really good for your skin. But getting a few rubber done, it doesn't actually get into your skin when you rub it on.


    Lisa: Right. Don't waste your money on expensive cream.

    Prof. Margreets: We know that... That's right. We know that it makes collagen juicy. So the enzyme that makes collagen, that needs vitamin C to work, was the first member of a family. Of about at the moment, there's about 60 members of this family. So, and apart from making collagen, they do all kinds of other things. So including regulate all about gene expression. So what we've discovered is that, it's really important to support enzymes that determine how your cell function changes. So…

    Lisa: It reads the DNA so to speak. So this enzyme, one of these enzymes..

    Prof. Margreet: These enzymes apply or remove marks from the DNA that say, ‘Read this gene, or don't read this gene’. And that's changing all the time. As cells respond to different stresses in different scenarios, and go through different growth phases. And vitamin C turns out, is absolutely critical for that process to be working well. And so you know, sort of…

    Lisa: This kind of fit everything in the body. Pretty much like every single cell in your body.

    Prof. Margreet: To greater and lesser extent.  And so that said, that's at the most fundamental level. It seems that that process is actually quite extraordinarily sensitive to changes in Vitamin C. So, I kind of make the analogy, about a car running, when running on three cylinders, or two cylinders, instead of four cylinders. Yeah, you can still get it to go along the road. But, you know you're not getting the best ride…

    Lisa: Not the best of your motor.

    Prof. Margreet: ...that you might get. And so you know, it is we're discovering so many things, so many fundamental processes that require vitamin C to work optimally. And also that they are responsive to small changes relatively small changes in vitamin C status. So there are mood enhancing enzymes that do the same thing. We've just published a study with students from Otago, who are all extremely well. Probably one of the wealthiest populations we've ever studied but they don't eat well. When we gave them kiwi fruit today, it just brought their vitamin C levels up. They felt well, then they’re already well. 

    Lisa: They're already healthy. They don't have...

    Prof. Margreet: They are surely well. So, they wereand even not at the extremes of deficiency. So it's like you can… we should be where animals areoptimal all the time.

    The dialogue around vitamin C for decades and decades was about avoiding deficiency. The only thing that became a problem was when you had scurvy, and were dying, and anything else was fine. And so what we're discovering now is thatit’s not fine. You need to be the best you can be in order to avoid all kinds of scenarios. So it's…

    Lisa: It's about optimizing…

    Prof. Margreet: Probably the most, of all the vitamins that we'vewell actually, vitamin B6 has a very fundamental… But probably the most diverse in that section of all the vitamins. So it's doing many things, in many places that affects an awful lot of functions.

    Lisa: So we're talking like inflammation, wound healing, infectious states, and controlling infection. We're talking about skin collagen production...

    Prof. Margreet: Absolutely, our brain is loaded with vitamin C.

    Lisa: Well, it is one of the biggest users of the vitamin C.

    Prof. Margreet: Yes, yes. So it's… Our brain is very hungry for vitamin C. So it's near for many reasons, including the support of molecule size serotonin, which is like your feel good moods. The production of other hormones that regulate mood reproduction. 

    Lisa: Yes. Yes. Yes. 

    Prof. Margreet: The list goes on and on.

    Lisa: My mind just goes wow. This could help with things like brain injuries, which I'm heavily into helping...

    Prof. Margreet: Yes, absolutely. Absolutely.

    Lisa: And RDA is one of the lowest in the world, isn't it? It is 45, I think milligrams or something ridiculous. That is not okay. Why can't we get this changed? You know we need 200 to 500 at least, don't we?

    Prof. Margreet: Yeah, there is a recommendation from the Ministry of Health that 200 milligrams a day as the recommended target for wellness. But RDAs are a confusing measure because they're actually the number at which 90% of people will avoid deficiency. So which is, right at the bottom, what do we need, in order to not die, basically? And so that message gets a little bit confused with, ‘This is how much we need, total’. And so 45 milligrams a day is, most countries around the world have up to the limit to at least double federal muster around 100, which is still in the minimum. But we just want bet our aims to get the New Zealand RDA… 

    Lisa: So maybe say one of your cats in a… I think it was work by Dr. Levine or [29:00] Maggie’s showing the rates from the 45 milligrams type thing up to 2.5 grams a day. It was a steep curve. Well, 50 milligrams in 500, where you get a huge benefit and then, even if you wanted to optimize, you could go even up to two and a half. 

    And of course then if you have one, oh no some horrible disease, or you have a lot of stress, or you have cognitive issues, or you have sepsis, or you have pneumonia, and then you may need like up to I don't know how many times. And that's one of the questions, isn't it? That you are trying to elucidate is that, ‘What are the dosages that we need’? 

    Prof. Margreet: That’s right, and I think we were hoping to hit, as instead of seating a whole new RDA for everything, is to have a recommended intake for different conditions. 

    Lisa: Absolutely.

    Prof. Margreet: So that you'd know if you hit a few, or if you do have a medical challenge of some sort. They use vitamin C infusions for burns patients.

    Lisa: Yes.

    Prof. Margreet: Because we know that burns patients chew through vitamin C. So that kind of massive inflammatory response does require your body who needs to be given a lot more vitamin C. So there is your, I can recommend it to intake for burns patients. 

    Well, if we knew that, when you have the flu, ‘Here's your recommended intake’. But when you have, if you have issues with this or that, you should be taking this amount. So which I think might be easier for people to get their head around than just one level, because we think that if we sit a daily intake aimed at alleviating illness, then that's normally not that achievable through our daily diet. And so you can't see it as an unachievable target for people to take vitamin C that they can't get from their diet because... So we always recommend food first and that is, so, 200 milligrams a day is what you would get if you did as you were told, an eight five plus. One of those five of the high vitamin C food, then you'll be fine. 

    Lisa: You're in the range.

    Prof. Margreet: So easily. So one kiwifruit, or some capsicum or a good amount of broccoli, or just if you can mix it up. But if you are eating a good range of fresh fruit and vegetables, you would be there.

    Lisa: But if you're eating just bananas or something that is on the five a day, but isn’t  high on the vitamin C level, you won't be meeting those recommendations. So we need to get a little bit more specific. 

    I want to go now into the cancer story, because I know like in the 1970s, Linus Pauling, who was a brilliant man, double Nobel Prize-winning scientist, sort of jumped in two feet firstif you likewith cancer. His studies that he did with cancer and vitamin C have extended the lives of these cancer patients that he was dealing with, four times as long. 

    But he sort of started a storm—if you likeof controversy, because back then there was no mechanism of action that was understood as, ‘How could this be happening’? And from there, it was sort of, plucked out of the year. Where is this vitamin C thing’? 

    You and your colleagues around the world have now sort of elucidated some of the mechanisms of action, and actually given some validity to what Linus Pauling was saying and later researchers.

    So now if we go into the cancer story, there's stillI mean I've lost two friends this week to cancer. We desperately need this research to be completed or furthered fast. So if there's any wealthy people sitting out there, if you want to support this sort of research, and is absolutely essential, because we're losing people left and right to these horrible diseases like cancer, like sepsis. We know that they're going to be beneficial. But you've actually discovered, so the HIF. I wanted to talk about the HIF protein… the HIF-1.

    Prof. Margreet: Yeah, that's the protein that I was mentioning…

    Lisa: Yes, earlier when I'm…

    Prof. Margreet: It’s also active in the white blood cells. 

    Lisa: Yes. Can you explain what the HIF protein does in regards to tumor growth, and why vitamin C is so important in regards to that.

    Prf. Margreet: Okay. So what is that, that's an acronym for Hypoxia-inducible Factor. Scientists are great at giving meaningless acronyms to meaningless terms. So, it’s a protein, it's what we call a transcription factor protein. So it's a protein that travels to the DNA, and switches genes on and off. These are master regulations proteins in these families of transcription factors. 

    So HIF is a major transcription factor that is present in all our cells all the time. Its role is to respond to low levels of oxygen. And so, if for some reason our oxygen supply is cut off. For example, if you had a tourniquet applied to a part of the end, and you cut off your blood supply, those cells in that tissue would get hypoxic. We need that not to die off. We need that to survive, that tissues, that when you restore the blood supply, that everything's actually fine. That's the normal function of the HIF protein, under conditions of low oxygen, just switch on a survival response. 

    It also does that, if you know has a lot of responses to basically regulate oxygen around your body. So it will, in areas where there are poor blood vessels, it will regenerate new blood vessel formation. You can't live without this protein. So we can't generate an animal that doesn't have it, doesn't survive beyond birth. 

    So this process is hijacked by cancer cells. So if you imagine, you will have seen pictures of a growing tumor starts off as a few cells. When that tumor, when that little clump of cells gets to be two millimeters across, it's very small, that doesn't have its own blood supply. And no oxygen will get to them, will get to the center cells, and they'll die. And this two millimeter tumor will die off. So but what happens when those cells run out of oxygen, because they switch on this HIF protein. And so when that switched on, those cancer cells now say, ‘Aha, I can make new blood vessels’.

    Lisa: They grow.

    Prof. Margreet: And it does that, it makes new blood vessels, can grow bigger. And as it grows bigger, every time it starts to run out of oxygen in the center, it makes new blood vessels. And so the tumor can grow, and grow, and grow. As well as switching on that formation of new blood vessels, it also turns those cancer cells into, ‘If I'm not getting enough oxygen, I need to get my energy from sugar now. I can't use our oxidative mechanism of energy creation’. So they become glycolytic. So then they start to depend on sugar for energy. We know that this is a property of tumors, that they're totally switched on to that. And when they get switched on to that, they stay on that. And so then they're able to become acidic, and they get all of these properties that cancer cells have. And it's all switched on initially by this protein. 

    And so the more HIF is expressed in your cancer cells, the worse offthe better off the cancer is, and the worse off patient is. So there's a huge effort being put on to trying to switch HIF off than cancer cells. Unfortunately, switching it off is not as easy as switching it on. And because it's switched off by a mechanism you have to turn on. And so the turning on of that mechanism requires either supplying of these enzymes. The switching off of HIF is done by these enzymes that need vitamin C. So when you supply vitamin C, you're then supplying energy to the off switch. And the off switch will dampen down that tough response. So that means doesn't come on as easily, you know, much how you keep it going... 

    Lisa: Not grow as fast...

    Prof. Margreet: And the HIF is ramped down and the cancer will grow more slowly. So that's one mechanism that we have now very good evidence for, indicating that giving vitamin C to cancer cells…

    Lisa: Slow tumor growth treatment 

    Prof. Margreet: … is a really good idea. 

    Lisa: So this, I saw another one of the charts with the mouse model that you had on the tumor growth showing the ones who had the vitamin C, the tumor growth was much slower than the ones who didn't, so that was because the HIF was switchedin effect switched off by the vitamin C.

    Well, I'm excited about this research, I really am. Because it's going to save lives. And this is the whole point of the call. And I don’t know if this conversation gets a little bit scientific, but hang in there with us people because this stuff's really important for life. 

    So can this prevent cancer? So if I want to be prophylactic, I want to be like, I don't want I've got cancer, perhaps genetically in the family, and I've got a higher risk. Can I take higher dosages of vitamin C with the hope of keeping the HIF from ever been switched on? Would that mean...

    Prof. Margreet: We know that having optimal vitamin C makes it harder to switch that HIF on. The other thing we know, it's very hard to prove any kind of preventative action, because you need to have huge studies to do that, with thousands of people. Those studies that… there's a lot of epidemiological work out there that has looked at people's vitamin C status, and their susceptibility to different cancers. And so, but there can be many factors can play a part in that, and we don't know whether that's just the HIF, or whether that's a boost in your immune surveillance, or whatever functions there may be. But many cancer rates significantly decreased by up to half for a number of cancers, if your vitamin C status is good rather than bad. 

    Lisa: Wow. Being over the 50 micromolar level... 

    Prof. Margreet: Yes. So if you’repeople who are that kick themselves to optimal level, have lower incidences of many diseases, actually. And they live longer, and just all measures of well-being are improved. But they also have much lower cancer rates.

    Lisa: Wow, so there's a reason, even if we don't have the whole answer yet for dosages and so on, would be to keep your vitamin C levels at the optimum, not at the minimum, your entire life, if that’s possible. What you mentioned before that there is a technology that's perhaps underway, that will be able to just, with a fingerprint, a prick of blood, be able to tell us what is in our blood, that would be amazing. I want one of those exactly where we are.

    Prof. Margreet: I think your doctor’s surgery once…

    Lisa: Yes, they definitely don't, because that would be just gold. I mean, in a situation like with my dad at the hospital, I couldn't get a vitamin C test to prove that he had a nutrient deficiency and so therefore, didn't treat the nutrient deficiency because I couldn't do the test.

    Prof. Margreet: Yeah, it's very difficult. It's a very… it's not an easy test to do. And so a lot of standard labs don't do it regularly. So you got to be fussy with the blood sample. And it's often a challenge in a clinical setting.

    Lisa: Okay, I hope that they do manage to do this because this would be very beneficial for everybody's health, because it's everything from heart disease to bloodwe mentioned collagen to having good skin, to all of these sorts of things. But we would be well advised to make sure that we are getting our optimal vitamin C dose. 

    Is there a danger, like I’ll be completely upfront, I have an intravenous vitamin C once a week at the moment and my mum's on it for once a week. I won’t keep that up forever. I'm also taking oral vitamin C as well. I usually take between two and four grams a day, and I'm not saying that I recommend that for anybody but that's just what I'm doing because I want to... There is no toxicity with vitamin C, is there? There's no risk, I mean on one hand an expensive way but that's...

    Prof. Margreet: Yes well. No, no toxic dose has never been identified, provided you have good kidney function. So you do need to be on the clear. If you can't clear it, or if you're dehydrated, and you're not producing any urine, you'd need to be on the clear because it will oxidize in your body. And when it does, those oxidation products need to be cleared out. And so you know it is, that’s the waiver. 

    So your body clears it to 100 micromolar for a reason because you don't actually want to have massive amounts running around all the time. And providing your tissues is saturated, any additional excess that you put on, it's not going anywhere, just going out.

    Lisa: So I had down Dr. Ron Hunninghake on the podcast a couple of weeks ago there. He's a doctor from the Riordan Institute. I don't know if you know the Riordan Institute. And he said he's overseen personally as a doctor over 200,000 IV, vitamin C sessions, if you'd like. And I said to him, ‘Well, you know, one of the arguments that I face with doctors with my dad, was that it could damage his kidneys’. Apart from the fact that they did damage your kidneys too, which was my argument back. They said that kidney stones could be an issue. And that was one of the problems. 

    Dr. Hunninghake, I posed that question to him. And he said in his 200,000 IVs, he's had three people with kidney stones, but they all had them previously. And he doesn't think there isagain, he hasn't done the clinical studiesbut he doesn't think that there is a huge risk for kidney stone formation that is also dependent on the calcium being in the kidneys from what I understand. So that that is one of the arguments. That is…

    Prof. Margreet: That's right. Yes. Because it’s the thing you will hear. It’s the first reason why you wouldn't want to take vitamin C. And I think we are trying to… it is important that you can clear it. So you do need, and I think for, rather than causing kidney injury, you don'tYou need a functioning kidney. You need functioning kidneys to clear it. Otherwise, you will end up with problems. But anyone who's given an infusion is usually tested or checked for that. But...

    Lisa: Or in a case, like with dad’s, there wasn't any option. So like, it was that or nothing. He wasn't going to survive.

    Prof. Margreet: You only need to clear... as long as you're making urine. Unless your body is, as you know, completely deficient. It is something that you need to lift. So it's a little bit… do say to people… if our patients are dehydrated, we give them a drink, right? Because we give them fluids if they're dehydrated, we give them fluids. So if your body is missing something that it's supposed to have to function, should give them some.

    Lisa: Yes, it would be a simple thing, especially if we can test it.

    Prof. Margreet: It would not, it's not a big deal, really, to give them some. I think the cancer story is a little more complex than that. Because what we think with solid tumors is that,  because any amount of oral vitamin C has not been shown to benefit solid tumors paricularly. And what our hypothesis was, is that if you give intravenous vitamin C, you achieve a higher level in the plasma. So you're basically trying to get the vitamin C to the place where the vasculature is poor, which is that hypoxic center of the tumor. The oxygen can't get to because the blood vessels are poor, vitamin C can't get there either. And you need both to get there. So…

    Lisa: To kill the chamber basically,

    Prof. Margreet: ...to switch that HIF off in that place. So we think that if you give infusions, then that increased dose actually gets to that core of the tumor.

    Lisa: And this is where?

    Prof. Margreet: So this is where an infusion is an advantage than oral vitamin C. This is where Linus Pauling got into, where he got into strife bit, and he was giving intravenous doses. He maintained that they had an additional benefit. The conditions at the time, didn't believe that. And they repeated his experiments with oral dosing, and found it to have no effect. And so he didn't, that time we didn't know about half, and he didn't. So he was arguing back and forth. And so it just became a bun fight, actually. There was no resolution, and a lot of acrimony, and never did the cause any good for him, or the clinicians either, and certainly not the patients.

    Lisa: This is such a shame, really, because it is also something.

    Prof. Margreet: So, kind of tone was set at that time. And, and it's taking a long time to pick that conversation. I think now we have not only the health mechanism, but we have these epigenetic, or the genetic regulatory enzymes that are also involved in many cancers. And in fact in a number of cancers, those enzymes are the mutated enzyme. They're the mutation in those enzymes that will drive the cancer. It's very common in hematological cancers, common in some glioblastoma, so brain cancer, and bowel cancer. 

    So there are two mechanisms whereby vitamin C might work. And so, we have just recently shown with myeloid leukemia that if you have a mutation in that enzyme, and you give additional vitamin C to those cancer cells, then… So if you have a mutation, you have two copies of every enzyme. If you take one out, 50% left. That 50% is trying to do the job at a hundred percent, and it isn't able to. So if that enzyme, that last 50% needs vitamin C given a vitamin C boost, within upping its level, you can upregulate it. And we think that it's now restoring normal function to thosethey didn’t stop behaving like cancer cells... 

    Lisa: And actually...

    Prof. Margreet: ...and just behave like normal cells. And so this would be a great treatment adjunct for chemotherapy.  Famous illogical cancers, because you now have cells that would respond normally rather than be these aberrant, crazy cells. 

    Lisa: I know that you had a case, so I won't mention the name in case and that's not okay. But I know that you…

    Prof. Margreet:  Oh, it is okay to mention the name.  Because Anton's family have actually asked me to mention his name.

    Lisa: Okay. So yes, I heard about Anton Kuraia's journey with leukaemia and how he had intravenous vitamin C, and that put him into remission. And he unfortunately lapsed later on and if you pick up the story there, but you got a tissue analysis, or you managed to get some tissue when he relapsed later on. In the two enzymes, the TT2, is it? And the W . . . 

    Prof. Margreet: That's one of these enzymes. So Anton is the case that we've learned a lot. And he, very generously when he read that… So he had this turn around, like a miracle response to vitamin C. And which really piqued our interest at the time we didn't know about the TT enzymes, and I almost lost my money on that. And thought, he wouldn't surprise me if he had one of these mutations, but he was in complete remission for two and a half years. And while he maintained a vitamin C regime, so he was taking it continued with intravenous vitamin C, each injectable, for couple of weeks, or something during that time. And when I spoke with him, I said, ‘You know what? I'd really like is I'd like to figure out just why this has happened and lapsed some of your cancer cells. But you haven’t got any sign’, which is great.

    Lisa: Yes, which is great. 

    Prof. Margreet: And we had no idea, quite what was going on, and how long that remission would hold for. And, unfortunately, two and a half years later, he relapsed. But at that point he said, ‘You know how you wanted some cancer cells? Well, I have some, and I don't want to know that’. But he pushed through and sent us a sample. And it was of his bone marrow, which, we had one sample, and I'm like, ‘Well, we need to think about what we do with this one’. We had a really good plan. And, and we managed to get a bit of funding from the local bone marrow cancer research trust for a project. And they're like, ‘If you got a good project’, and I’m like, ‘I do actually have a really good project’. 

    So I put a young post-doc onto that, who has been absolutely marvelous, and together with the clinicians in Auckland, we tracked down the risks of Anton samples that were in the Auckland clinic, and ran the DNA analysis, the genetic analysis on his cancer, and discovered that he had not one but two mutations that involved a requirement for TET2 activity. And so both of the clients, so myeloid leukaemia is a clonal disease. One clone can have one mutation, another clone can have another mutation or both. They're two clones, each one with a mutation that required TET2 or a feature TET2 activity. Both of those clones were wiped out by the vitamin C. 

    Lisa: Wow. So they kicked them alive?

    Prof. Margreet: Yes, yes. But what we discovered was that, that didn't wipe out the cells completely because that one of the clones came back.

    Lisa: Was it because he stopped the vitamin C, like if…

    Prof. Margreet: What we discovered was that when it came back, that clone had acquired additional mutations, as they do often. And so cancers do that, they cause you to be more and more aberrant as it continues. So the original mutation was still there, but so were additional mutations. And so the second time around, the vitamin C treatment worked a little bit. It seemed like it was trying to work. He went and had more chemotherapy. And then that didn't work, got sent home again. With weeks to live anyway, back onto the vitamin C, and got better. But the blood cell count never came down to zero again, and…

    Lisa: So basically the cancer was stronger the second time with more aberrant mutations.

    Prof. Margreet: Yes. But he didn't, he didn't seem to know what's going on. But my gut has got really good.

    Lisa: So something was, so that brings in the quality of life because that's proven, isn't it? If you're having to have chemotherapy, and having vitamin C can be very beneficial for quality of life. Least fatigue, least nausea, all of those sorts of horrible things that happened to poor chemo patients can be...

    Prof. Margreet: That’s a story we believe, of just replenishing the depleted supply in your body. So basically, you're giving your body these toxic cocktails, you're expecting your body to function, and then respond. And at the same time that's running out of a vital nutrient. And so if you, if you can restore that, then your fatigue levels… so one of the things that vitamin C does is it supports the promotion of energy. So it regulates adrenaline. Absolutely key to making adrenaline, to making molecules that support energy production, energy metabolism. 

    And so, if you're starting to run low on those things at the same time as you're undergoing the chemotherapy, what can be written off as a side effect of the chemotherapy can be alleviated. A few can restore some of those normal functions. So a lot of the kind of brain fog, things, ability to concentrate, mood things, pain, and nausea and fatigue, a lot of the measures improve.

    Lisa: Wow. So that alone is a reason to be considering it.

    Prof. Margreet: It's a very important consideration. 

    Lisa: Absolutely, it’s quality of life. 

    Prof. Margreet: Absolutely, as far as we can tell, it does not interfere with any other cancer treatments. Because that's the other worry that people have, doctors have, that, ‘I don't know, because it might interfere with the treatment I'm trying to give you for your cancer’.

    Lisa: And this is a problem when people go to their oncologist, their local oncologist. They’d be saying, ‘Don't do vitamin C’. This is why this information is so key to be able to share it.

    Prof. Margreet: Well, that's why we tried to do the research. Because doctors have the patient's best interests at heart. And they worry when patients come in and say, ‘You know, should I take this? Can I take that’?and they're throwing everything they can at the cancer. And they worry that something else that you’re doing might work against that. And so they are always very cautious and rightly so. Because we want our doctors to be working from evidence, from an evidence base. 

    And currently, we don't have those answers here. That we can absolutely say… I mean, this is why we're working so hard to try and identify the causes, and how vitamin C is working. So that then we can give that information to the clinicians, who can then put that together with their patient information and say, ‘Well, for you on this drug, this will be fine. You do that, you know, and in fact, it will help with this and this and this’. So or, ‘Under these circumstances, now, I'd rather you didn't do that, until you've got this out of the way’, or whatever. So we can manage better advice and give patients an idea as to what they can expect. 

    So like, with the haematological patients, we’re starting to identify what genetic subgroups of the cancer might respond. So then you might be able to say to you, to a cancer patient, ‘Looks like you've got this mutation. This is very likely to be helpful for you’, or ‘It looks like you don't have this mutation. It's unlikely that it's going to help you. You can try, but it's unlikely’. So we can be a little bit more…

    Lisa: more nuanced?

    Prof. Margreet: …real, rather than just a kind of blanket response.

    Lisa: The hard thing is and when people are in dire straits. You haven't got the luxury of waiting another 10 years perhaps until the research is done. And so you're in this catch 22 type of situation. And you have to, as a patient or looking after a loved one, sometimes make calls on the direction that you are going to go based on this that you acknowledge without actually having 100% proof in. This is an argument that nobody can really win because I mean, it's a really tough situation. 

    And I certainly, with it with my dad, but in with my mum's story as well. And so I understand the frustration of people and what they’re going. But with Anton for example, he obviously went and got the intravenous vitamin C, prior to it being proven to help, and it obviously gave him a few more years. 

    Prof. Margreet: That's right. And at the moment, we're at the point where we're learning a lot from patients like that. If he hadn't done that, he hadn't done that, no one would have done it. And we wouldn't know what we know now. And we're learning from other patients like that, as well. So let's see…

    Lisa: Anecdote versus...

    Prof. Margreet: So there is anecdotal evidence, what I say to people and often get asked by cancer patients, ‘Should I do this or not’? One of the things that we're learning and we've learned, we are moving the story forward. The things that we've learned, even from Anton's case, is that vitamin C is not probably not going to kill your cancer. So in his case, even when he went into complete remission, the vitamin C was controlling his cancer. That was it. It didn't eliminate it. So that knowledge is gold.

    Lisa: Yes. Actually.

    Prof. Margreet: And because that gives us an insight into how we might manage that in the clinic. If we were going to do this in the clinic. We would know that if we're seeing a response from a cancer patient, we're seeing a good response to vitamin C, there’s an opportunity. It buys you more time. But it can give us insights into how we might work better than with other treatments. So that information is gold. 

    The one thing that you know, I can understand entirely how any individual cancer patients like, ‘Well, I need the answer now. I have this in my own life, with my husband. I'm not waiting for the research. I’m not going to wait for that’.

    Lisa: Exactly.

    Prof. Margreet: ‘You need to announce it now’. But suddenly my priorities can then change upfront. I now have voice inside and I want, ‘We want an answer now’. And so, as far as, you know, the vitamin C treatment does, I often think, ‘Well, what would I do myself’? And I think from what we know now, knowing that, we know, there will be a quality of life benefit. Almost certainly. And that in itself would be worth raising payment for. So just to alleviate, as many of the horrible scientific treatments, and the disease itself. 

    Secondly, is that, if what we know is that if you are going to see a benefit from vitamin C infusions in cancer, you would see it quite quickly. So, this is not something that would take months and months to manifest. So, if it were doing something, you would notice something quite, quite soon. I mean, Anton's case was quite remarkable. In a case with a cancer like that, within two weeks he was beating it. Nearly tears. 

    Lisa: From nearly dead to better. 

    Prof. Margreet: A month later, he had a bone marrow biopsy taken. And he was back to normal. So if it's going to work, and I think even with a solid tumor, if it were having a beneficial effect, you will know quite quickly. 

    Lisa: So it's worth doing. 

    Prof. Margreet: So if you wanted to try, then you first try, but you have to pay to try. 

    Lisa: You have to find a doctor to do it. 

    Prof. Margreet: So it is, there are good people around who . . . It’s an unproven treatment.

    Lisa: And that's what you're working on. 

    Prof. Margreet: And so, we're trying to move that story forward. It's inordinately slow.

    Lisa: And it's a shame that the arguments, or the problems, the controversy that has surrounded the original research, if you like, has colored some of the reactions you get, now. You get this polarizing effect that hopefully reason will calm things down eventually. We can just talk about the scientific evidence, the evidence, the evidence, the evidence. And then perhaps we can just bring it back down to a non-emotional level. Because as a loved one who's just lost somebody, because I believe we could have had a chance to get him back, my dear back, if we had had access to vitamin C from day one, but not day 14. It's hard not to be emotional about that. 

    Prof. Margreet: Absolutely. It really is. And I can understand that entirely. And this is why we're not giving up.

    Lisa: Yes. But it's so important, the size, it’s so important.

    Prof. Margreet: But the controversy around this is what it is. I’m trying very hard to walk a line between that were drawn by either side. And my argument is always, for what do we actually know, and what if we actually measured? 

    And let's just stay with it? Because we can… I thought that's what I’m trained to do, actually. So that's what I should do. The narrative is being influenced, I think the discovery of the new enzyme activities is helping a lot. Because people are starting to see how it might work. And just showing how it's working, is very key to getting people to accept what just what they need to do. So, little by little. 

    Lisa: Little by little we’ll get there. 

    Prof. Margreet: Little by little, I hope I live long enough to...

    Lisa: Long enough to… yes. In the meantime, we can make our own educated… This is whatthat you've coming from a scientific background, I'm coming from an anecdotal background, or a background of I have to make decisions, life and death decisions for my loved ones. I'm going to take certain risks because the alternative was not a good one. And so, I think bothas a loved one of a patient, I desperately need that research to be done. I want that hurried up. We all want it, we want the results. 

    Prof. Margreet: Me too. I want it hurried up.

    Lisa: And meanwhile, I'm going to make some educated decisions myself, on what I do for me and my family. And I think that's the best approach that we can do. Because we can't always wait until, when we haven't got the timeline, when we love somebody who's sick. And so we’re headed to make those educated decisions ourselves, and then live with the consequences. 

    But what I think is important that we have informed consent, informed discussions around these things, and that we try to take the emotions out of the whole thing. And actually, instead of—in the hospital I was sort of shut down because, ‘You're not a doctor, and you don't know anything’. And that's not true. And there was no willingness to even look at the clinical studies that I presented, that they were coming from my doctor friends who are supporting me on the outside, to try to present this on the inside of the hospital. It came down to legal arguments, more than anything else. And that's frustrating to think that perhaps you lost somebody because of a legal situation. The work that Dr. Merrick has done in this area and Dr. Berry Fowler, who’s coming on the show next week. It’s really, really exciting for me.

    Prof. Margreet: Well, those two clinicians have some very compelling stories to tell. I do, I do understand. I understand entirely, that I sit here in my office just above ambulance bay watching, and above the ICU board, and seeing…

    Lisa: seeing people struggle every day,

    Prof. Margreet: …thinking, there are things we could be doing better. And it is about getting those conversations going. So far, I think we're getting good traction in New Zealand with getting with conversations. But it's, it is extremely…

    Lisa: It is extremely slow. But then you and Doctor Anitra Carr, looked at his stuff as well. And that's exciting that we are making progress. And so I just want to, we've covered a lot of ground today. And we've really gone through in all sorts of places, but I just want to thank you for your sacrifice, because I know this is a huge amount of work. This is your life's work, basically. And I don't know if everybody was recognized for what their contribution, they're actually making to humanity. And I think and what you're doing is just absolutely wonderful. So thank you, because it is going to save lives. It has, has already saved lives. 

    Prof. Margreet: Well, I don't know that I have. But we have some wonderful colleagues globally as well. And so, there is a network of people who support each other on this, and some very good people doing excellently in a lot of places. Quote Mark Levine. What that man has done is extraordinary. In terms, he has provided the best information that we've ever had on vitamin C. With his own interesting stories to tell about how his colleagues’ treated... 

    So, some wonderful work has been done, and eventually people will just see. Actually, this is just, I just keep saying, this is just a thing that we need to eat. It's a vitamin that we need, an orange to keep our bodies functioning. Just like we need food, and we need to breathe, and we need water to drink. Now, we don't argue with those things.

    But this is just one of those things, when we need to figure out how we do this, how we do this piece. And under what circumstances so, you know, let's try to take the emotion out of it…

    Lisa: Yes, you're very good at it. 

    Prof. Margreet: I think it's the only way forward. And to give people the best information so they can make fit, so they can make the right choices, so clinicians can be making informed choices that they know is for the benefit of their patients. Because our clinical people, they're at the coalface and, and they’re having to make life and choice decisions for their patients all the time. And so they have high degree of caution around that. And that's what we want from them. So we need to provide them with the best information that we can get for them to make those clinical judgments.

    Lisa: I think that's a perfect place to wrap it up. Professor Margreet Vissers, you've been absolutely wonderful. Thank you so much for the work that you and your team are doing. Please continue. And if there are any rich people out there listening, please fund this research. Continue to fund this research because it's very, very important work and we desperately need it. So thank you for your time today.

    Prof. Margreet: My pleasure. 

    That's it this week for Pushing the Limits. Be sure to rate, review, and share with your friends. And head over and visit Lisa and her team at lisatamati.com.

    The information contained in this show is not medical advice it is for educational purposes only and the opinions of guests are not the views of the show. Please seed your own medical advice from a registered medical professional



    I am SO excited to finally get my FOREVER FRIEND, one of my very best girls, Keala Kennelly on the show for you.

    This Hawaiian-born badass is the definition of high-performance, not only in athleticism but also in the way she uses the power of her voice to advocate for the change and action she wants to see made in the world. 

    Kauai born and raised, Keala grew up surfing with icons like Andy + Bruce Irons, charging some of the island's heaviest waves and eventually competing against them in youth competitions. 

    She turned pro at 17 and began competing around the world on the WQS tour, quickly moving up to surf against the best on the WCT. She spent a decade ranked in the top 10 on the ASP World Championship Tour. And by 2003, Keala peaked as number 1 in the WCT rankings before ending the year as the 2nd best female surfer in the world.

    Being the multi-passionate crusader that she is, Keala decided to take a break from her surfing career in 2007 to pursue her love for acting and music (you might recognize her from the renowned film Blue Crush or the HBO series, John from Cincinnati). 

    It was in that phase of her career, Keala then decided to depart from the WCT tour, where her surfing felt limited to a certain style, and instead chase her passion for surfing big waves. 

    Keala has since been a true pioneer in creating groundbreaking performances on some of the heaviest waves, shattering glass ceilings and proving that women are just as courageous, skilled and BADASS as men in the sport. 

    One of her most outstanding recognitions, outside of being the current WSL’s Women’s Big Wave Champion, was becoming the first woman to be invited to compete in the renowned Eddie Aikau Big Wave competition at Waimea Bay-- I cannot express how BIG of a deal this actually is, especially as a born + raised Kauai girl.  

    Since Keala has cemented her presence in the world of big wave surfing, she has used her status to help establish a Women’s Big Wave Tour and holds a vital role in the committee that was responsible for winning the fight for women's equal pay in surfing back in 2018. This was a true milestone accomplishment for Keala, in her long list of accolades, and she now has her heart set on furthering this accomplishment as an advocate for equality in pay across ALL of women’s sports. 

    Here’s the thing you guys, with ALL of those incredible facts on Keala, I literally haven't even scratched the surface to my girl’s list of accomplishments + accolades. Some of the greatest accomplishments live outside of her career. Her resilience is remarkable. Her demonstration in how she battles mental health issues, how she has faced death and risen back from traumatic injuries, and what it took her to finally come out and show the world a truth she kept locked up within her during the earlier parts of her life.  

    To be fully transparent, this copy was a bit daunting at the thought of creating not only because it is a HUGE challenge to summarize my girl’s long list of accolades with brevity but also to reverently give you an inside view on the deep-loving connection that is multiple decades longs between KK and I. 

    The reality is I can’t.

    However, I do believe this powerful conversation with my hilarious, badass, always reaching for bigger, homegirl for life; will give you a killer glimpse of how amazing she is and how much she means to me.



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    Health is About the Little Things: Rangan Chatterjee, M.D. on How to Feel Better in Five Minutes

    Health is About the Little Things: Rangan Chatterjee, M.D. on How to Feel Better in Five Minutes
    As 2020 continues to unfurl in a fashion beyond surreal, more and more are descending into the anguished abyss of distress. Awakening to acrid tangerine skies that have transformed sunny California into a Blade Runner dystopia, I myself vacillate between melancholia and a commitment to forge a better world. When the darkness descends, I find sanity in focusing only on those things I can control: my actions and reactions. Nonetheless, waves of anxiety -- and sometimes even despair -- continue to break on the shores of my consciousness. It is in these moments that I resort to a battery of simple but generally quite effective contrary actions. I spend time in nature. Double down on meditation and human connection. I eat better and move more. And I extend myself in service to others. To further explore the many practical and unexacting things we can all undertake during this stressful time to course-correct our emotional disposition, reframe our reality and sustainably serve our well-being, I'm joined by my friend Rangan Chatterjee, M.D. -- who today returns for a third spin on the RRP flywheel. One of the most influential doctors in the U.K., Rangan is a pioneer in the field of progressive, functional medicine. He is double board-certified in internal medicine and family medicine, holds an honors degree in immunology, and has appeared on seemingly every prominent media outlet from the BBC to The New York Times.  In addition, Rangan prevails over the wildly popular Feel Better, Live More podcast. His TEDx talk, How To Make Diseases Disappear, has been viewed almost 3 million times. And he is the author of three #1 Sunday Times bestselling books. The focus of today's conversation is his latest well-being tome, Feel Better In 5. A close cousin to my podcast with Atomic Habits author James Clear (RRP #401), today's exchange is all about habit change and habit formation. It's about the power of bite-sized actions. And how, when undertaken regularly, short and simple practices can rapidly and completely change your health and life. We discuss the difference between breaking bad habits versus crowding them out with new, better habits. We explore the realities of food addiction. Our epidemic of emotional eating. And Rangan's personal theory on cause and solution. We talk generally about holistic health and lifestyle medicine, and why progressive wellness should be accessible to all -- now more than ever. Interspersed throughout, Rangan shares how he has helped patients relieve stress, find fulfillment, and engender peace in these chaotic times. But most importantly, we explore his very simple, almost effortless, methods for building a new and sustainable lifestyle to serve our long-term health. The visually inclined can watch it all go down on YouTube (courtesy of Zoom). And as always, the conversation streams wild and free on Apple Podcasts and Spotify. I always enjoy time spent with Rangan, even when it's remote. My hope is that you do as well -- and put his advice into action. Peace + Plants, Rich