Dr. Peter Attia, Journal Club

Sponsors: Eight Sleep, BetterHelp & Joovv

Light, Dark & Mental Health; Retina

Outdoor vs. Indoor Light, Cataracts, Sunglasses

Tools: Sunrise & Sunsets, Circadian Rhythm; Midday Light

Tools: Night & Light Exposure; Waking Before Sunrise

Article #1, Light/Dark Exposure & Mental Health

Sponsor: AG1

Odds Ratio, Hazard Ratio

Night vs. Daylight Exposure, Mental Health Disorders

Major Depression & Light Exposure; Error Bars & Significance

Sponsor: LMNT

Prescriptions; Environmental & Artificial Light; Red Lights

Nighttime Light Exposure; Sleep Trackers & Belief Effects

Light Directionality, Phone, Night

Light Wavelengths & Sensors; Sunglasses

Hawthorne Effect, Reverse Causality, Genetics

Artificial Sweeteners, Appetite

Natural Light Cycles, Circadian Rhythm & Mental Health

Article #2, Immune System & Cancer

T-Cell Activation; Viruses

Autoimmunity; Cancer & Immune System Evasion

Checkpoint Inhibitors, CTLA-4

Anti-CTLA-4 Study Drug (Ipilimumab), Melanoma

Patient Population, Randomization, GP100

Response Rate

Overall Survival & Response

Median Survival vs. Overall Survival, Drug Development

Gender & Dose

Adverse Events; Autoimmunity

Pancreatic Cancer; Aging & Immune System Health

Melanoma; Lynch Syndrome, Keytruda

Immunotherapy & Cancer Treatment; Melanoma Risk

Zero-Cost Support, Spotify & Apple Reviews, YouTube Feedback, Sponsors, Momentous, Social Media, Neural Network Newsletter

- The Huberman Lab Podcast's Journal Club series discusses papers on light exposure and mental health, as well as advancements in cancer treatments.
- Bright light exposure during the day and dark exposure at night are emphasized for mental health.
- A study found that both daytime light exposure and nighttime dark exposure have independent roles in mental health.
- Morning light exposure is prioritized over evening light exposure.
- Light exposure at night is important for mental health outcomes and is correlated with depression, self-harm, and worsened symptoms in bipolar disorder and PTSD.
- Diet soda consumption and obesity are used as an example of reverse causality.
- Caution is recommended when consuming artificial sweeteners, with a preference for xylitol and allulose.
- Immunotherapy is considered the most important hope for treating cancer, and engineering T-cells to be better at recognizing antigens is the next step.

- The transcript is from the Huberman Lab Podcast's Journal Club series with Andrew Huberman and Dr. Peter Atiyah.
- Andrew discusses a paper on the positive effects of light exposure during the day and dark exposure at night on mental health.
- He emphasizes the importance of getting bright light in one's eyes throughout the day and being in darkness at night.
- Peter presents a paper on novel treatments for cancer, highlighting the current and future technology and the role of the immune system.
- The episode provides valuable information on light and dark exposure for mental health and advancements in cancer treatments.

- The podcast is separate from the speaker's teaching and research roles at Stanford.
- The speaker wants to provide free information about science and science-related tools to the general public.
- The podcast is sponsored by Eight Sleep, which makes smart mattress covers that control temperature for better sleep.
- The podcast is also sponsored by BetterHelp, an online therapy platform.
- The podcast is additionally sponsored by Juve, a company that makes red light therapy devices for various health benefits.

- The transcript discusses the relationship between light exposure at night and various mental health conditions.
- It highlights that there is a strong correlation between increasing light at night and depression, as well as self-harm in the upper quartile.
- The relationship between light exposure during the day and PTSD and psychosis is also mentioned.
- Anxiety and bipolar disorder do not show as strong of a relationship with light exposure.
- The study's error bars indicate that the sample size is not overpowered, and the statistical significance of the findings is reliable.

- Element is an electrolyte drink with zero sugar and the correct ratios of electrolytes (sodium, magnesium, and potassium).
- Electrolytes are important for proper cell functioning, especially nerve cells.
- Drinking Element improves mental and physical functioning when well hydrated.
- The speaker drinks one packet of Element in the morning and during exercise, and an additional packet after sweating a lot.
- Element comes in various flavors and can be heated up in the winter months.

- People with a sensitive circadian mood system may need less daytime light exposure to feel good, but also need very little light at night to negatively impact their mood.
- Drugs used to treat bipolar disorder may be effective because they reduce the sensitivity of the light sensing circadian system.
- Certain antidepressants may suppress the ability for daytime light to positively impact mood.
- Darkness at night should be viewed as a treatment for bipolar disorder, and bright nighttime light exposure should be avoided.
- Different light sources have different lux levels, with moonlight and candlelight being relatively low, campfires being brighter but still not as bright as a densely overcast day, and phones or tablets at maximum light intensity being around 500 to 1000 lux.

- The speaker used to be strict about avoiding blue light in the evening, but now believes that the content on the phone matters more than the brightness.
- The speaker emphasizes the importance of considering the context and overall picture when it comes to sleep and light exposure.
- It is suggested that staying up late should be for enjoyable reasons, but acknowledges that there will be unavoidable situations that disrupt sleep.
- The impact of social media and sleep trackers on sleep quality and perception is discussed.
- The speaker believes that sleep trackers can provide valuable insights and act as behavioral tools, but recovery scores are not reliable predictors of performance.

- The speaker emphasizes the importance of natural light for our biology and overall health.
- They mention that people spend most of their time indoors, which leads to insufficient sunlight exposure during the day and excessive artificial light exposure at night.
- The speaker acknowledges that brief exposure to bright light at night, such as using the bathroom light, is not a major concern for disrupting circadian rhythms.
- They discuss the difference in light exposure when looking directly at a light source versus tilting it away, highlighting the importance of directionality.
- The speaker shares a story about their friend who tries to minimize light exposure from their phone at night by tilting it away.

- Sunlight includes the visible spectrum from 470 nanometers to 650 nanometers, which is blue and ultraviolet light.
- Red light is around 680 nanometers, while far red light is above 7720 nanometers.
- Humans can perceive light lower than 470 nanometers and higher than 650 nanometers.
- The study may have been limited by the narrow band of the wrist sensors used.
- Sunglasses filter out too much light, causing a significant decrease in the lux count reaching the retina.

- The transcript discusses the possibility of reverse causality in observations and correlations.
- The Hawthorne effect is mentioned, which refers to people changing their behavior when they are being observed.
- The example of diet soda consumption and obesity is given as an illustration of reverse causality.
- The question is raised about how much of the observed effects are a result of the condition being studied.
- The potential for examining the issue from a Mendelian standpoint is mentioned.

- The speaker believes that both body habitus and gut biome can influence beverage choice and metabolism.
- Some individuals find that diet soda stimulates their appetite, possibly due to the perception of sweetness.
- The speaker mentions a paired association between the sweetness of sucralose and insulin response.
- The speaker recommends caution when consuming artificial sweeteners, suggesting limited use and preferring xylitol and allulose.
- The speaker personally drinks diet soda occasionally and uses stevia, but generally avoids sucralose.

- The speaker believes that 65-75% of the effects discussed are likely due to direct exposure to light.
- The speaker acknowledges the possibility of behavioral factors limiting light exposure in depressed individuals.
- Circadian disruption and psychiatric health are closely linked.
- Bright sunlight in the morning increases the amplitude of the morning cortisol spike, which is beneficial.
- The speaker agrees with the assessment that there is a causal relationship between light exposure and mental health, possibly even at an 80-20 ratio.

- The selected paper is a landmark study on a class of drugs in cancer therapy.
- These drugs have only reduced mortality by 8-10%, but their method gives hope for the future.
- The human immune system is remarkable in its ability to detect harmful pathogens without prior knowledge.
- Autoimmune conditions are exceptions where the immune system attacks the self.
- The immune system's effectiveness against cancer and why it often fails to destroy it is a question.

- The transcript is from a Journal Club meeting discussing a research paper on light exposure behavior and its impact on mental health.
- The paper examined light exposure behavior in over 85,000 people in the UK.
- Seasonal affective disorder (SAD) is a well-known condition that is treated with exposure to bright light.
- The study suggests that both daytime light exposure and nighttime dark exposure have independent roles in mental health.
- The biological mechanisms involving retinal ganglion cells and the hypothalamus play a significant role in regulating mood and circadian rhythms.

- T cells recognize antigens, which are small peptides that can be proteins or carbohydrates.
- Antigen presenting cells sample peptides and present them to T cells using MHC class receptors.
- MHC class one is for antigens coming from inside the cell, while MHC class two is for antigens coming from outside the cell.
- T cells recognize antigens presented on MHC class one receptors and mount an immune response.
- Our ability to fight off viruses is a result of our immune system's constant vigilance and ability to destroy viruses without causing a systemic inflammatory response.

- Thymic selection occurs in infancy to teach T-cells to recognize self and not attack the body.
- Most cancers are genetic, but not necessarily inherited.
- Cancer cells behave differently from normal cells by not responding to cell cycle signaling and having the ability to metastasize.
- Cancer cells trick the immune system by secreting factors that dampen the immune response and by altering the surrounding pH.
- Contagious cancers are rare, but there are examples of cancers being transmitted between animals through physical interaction.

- Oncology has made significant progress in blood tumors and some lymphomas, but very little progress in solid organ tumors.
- The two breakthroughs in solid organ tumors have been in testicular cancer and a rare gastric cancer called GI stromal tumor.
- The top five causes of cancer death in Americans are lung, breast, prostate, colorectal, and pancreatic cancer.
- More than 80% of these cancers have antigens recognized by the immune system, but there are not enough T-cells or they are being inhibited from acting.
- One way the body inhibits the immune system is through checkpoint inhibitors, specifically CTLA-4, which can be targeted to unleash the immune system.

- The transcript discusses a phase three study comparing an anti-CTLA-4 drug called ipilimumab to a placebo in patients with metastatic melanoma.
- The study aimed to determine the impact on median survival and overall survival.
- The patients in the study had progressed through all standard therapies and had advanced stage three or stage four melanoma.
- Melanoma has a complex staging system called the TNM staging system, which includes factors such as tumor size, lymph node status, and the presence or absence of metastases.
- The prognosis for melanoma worsens as the staging increases.

- The study involved a three to one to one randomization, with three groups including a placebo group, an anti-CTLA-4 group, and an anti-CTLA-4 plus GP100 group.
- GP100 is a known cancer vaccine that has shown no efficacy in previous trials.
- The patient population consisted of individuals with melanoma, many of whom had aggressive cancers and a high likelihood of not surviving more than a year.
- The majority of patients had visceral metastases, and a significant portion had CNS metastases.
- The use of GP100 as a placebo was justified by the belief that it may have a different effect when combined with a checkpoint inhibitor, and it made it easier to enroll patients in the study.

- The primary outcome of the study changed from best overall response rate to overall survival.
- The study took place over a long period of time and across multiple centers.
- Patients had to undergo scans to measure their response to treatment.
- A complete response means the cancer disappears completely, while a partial response is at least a 50% reduction in tumor size.
- The overall survival rate for metastatic melanoma is very low, except for those who respond to high dose interleukin-2.

- The transcript discusses Figure 1, which is a Kaplan-Meier survival curve showing overall survival over time for three groups: control group, anti-CTLA-4 group, and anti-CTLA-4 plus GP100 group.
- The Kaplan-Meier curve shows a clear distinction between the control group and the two treatment groups.
- The transcript mentions the tail of the graph, which represents true overall survival, and notes that one person in the control group survived for 44 months.
- The median survival for the control group is mentioned as being low, but the exact value is not provided.
- Table 2 is mentioned as providing information on the evaluation of therapy, including complete responders, partial responders, stable disease, and progressive disease.

- The median response rate is an important metric that should be prominently displayed.
- Median survival for metastatic cancer has increased, thanks to treatments.
- Overall survival for solid epithelial tumors has not changed.
- Cancer drugs often focus on extending median survival rather than overall survival.
- There is skepticism about the pharmaceutical industry due to high costs and potential negative impacts on quality of life.

- The transcript discusses the approval of a drug called Keytruda, which has shown better results in terms of survival rates compared to another drug.
- The speaker highlights figure two in the paper, which shows that GP100 is not effective, particularly in females.
- The primary outcome of the trial was overall survival, and there was a 31% risk reduction in overall mortality when comparing the treatment group to the placebo group.
- The hazard ratio for the anti-CTLA-4 plus GP100 subgroup shows a 36% reduction in risk of death, but it does not reach significance in females.
- Other studies have also found that anti-CTLA-4 is less effective in women, and possible explanations include differences in immune response and dosing based on weight.

- Table three in the paper discusses the adverse outcomes of the drug.
- The majority of people in all three groups experienced some adverse events.
- There was not a significant difference in grade four toxicities between the groups.
- The NTC TLA-4 groups had higher rates of autoimmune events compared to the placebo group.
- Autoimmunity has been observed to correlate with response to the drug.

- There are two types of stimuli that cells respond to: bright light and long wavelengths of light.
- Daytime sunlight is correlated with elevated mood because it provides a lot of bright light.
- The sun provides over 100,000 lux on a sunny day at noon, while most indoor environments only have around 4,000-6,000 lux.
- The circadian clock sums photons and is an integration mechanism, not triggered in a moment.
- Sunglasses should be avoided in the early and later parts of the day to maximize exposure to sunlight.

- Keytruda was released around 2013-2014 for the treatment of metastatic melanoma.
- Pancreatic cancer can be non-survivable, especially if it is unresectable.
- The Whipple procedure is a surgical procedure to remove the head of the pancreas, but it may not be effective if the cancer has spread too far.
- Removing the whole pancreas is not a viable option because the cancer has already spread.
- Modulating the immune system as we age may be important in preventing cancer, and drugs like rapamycin could potentially enhance cellular immunity.

- Melanoma and kidney cancer have more mutations, making them more likely to produce antigens recognized as non-self.
- Checkpoint inhibitors were initially studied in metastatic melanoma due to the higher chance of success.
- A patient with Lynch syndrome, a hereditary mutation that increases cancer risk, had a complete regression of pancreatic cancer after receiving Keytruda.
- The treatment activated the patient's immune system to the point where it destroyed his pancreas, resulting in type 1 diabetes.
- The paper mentioned did not comment on any correlation between autoimmunity and treatment response.

- Immunotherapy is considered the most important hope for treating cancer.
- The overall survival rate for patients with metastatic solid organ tumors has increased by about 8% due to immunotherapy.
- The next step in immunotherapy is to engineer T-cells to be better at recognizing antigens.
- Tumor-infiltrating lymphocytes (TIL) are wise but too old to effectively combat cancer.
- Sunburn, rather than sun exposure, is a significant risk factor for melanoma.

- The speaker asks listeners to subscribe to their YouTube channel, Spotify, and Apple podcast.
- They mention the importance of leaving a five-star review on Spotify and Apple.
- The speaker encourages listeners to check out the sponsors mentioned in the episode.
- They discuss the benefits of supplements and direct listeners to livemomentous.com/huberman for more information.
- The speaker promotes their social media platforms and encourages listeners to follow them for science-related content.

- There are four types of light that are important for optimal health, particularly mental health.
- Cells in the eye compare and contrast blue light and longer wavelength light to trigger signals to the circadian clock.
- Low solar angle sunlight in the morning advances the circadian clock, while low solar angle sunlight in the evening delays the clock.
- Midday sun is not effective for shifting the circadian clock.
- It is better to prioritize morning light exposure over evening light exposure, as most people already have some artificial light exposure in the evening.

- Dark exposure at night is important for mental health outcomes, even if not enough sunlight is received during the day.
- Accurately timed light exposure to the eyes is valuable for mental health.
- Some people are more resilient to light effects than others.
- Light exposure to the eyes is relevant, not the color or darkness of one's eyes.
- Morning and evening sunlight exposure is especially important for kids, as they spend most of their time indoors.

- A recent study published in Nature Mental Health suggests that getting ample sunlight exposure during the day and avoiding excessive light exposure at night can greatly benefit psychiatric health.
- The study builds upon a previous study that established the positive effects of spending time outdoors on mood, sleep, and circadian rhythm.
- The new study specifically focused on individuals with major depressive disorder, generalized anxiety, PTSD, and bipolar disorder.
- The researchers equipped participants with wrist accelerometers to measure ambient light, although measuring light at eye level would have been more ideal.
- The study found that greater light exposure during the day was associated with a lower risk of psychiatric disorders, while greater light exposure at night was associated with a higher risk and poorer mood.

- AG1 is a vitamin mineral probiotic drink that contains adaptogens.
- The speaker started taking AG1 in 2012 and continues to take it daily to meet vitamin and mineral quotas and support gut health.
- Gut health is important for the immune system and brain functioning.
- AG1 provides specific micronutrients that are hard to get from whole foods.
- The speaker recommends AG1 as a supplement that supports mental health, physical health, and performance.

- The study examined the association between light exposure and psychiatric outcomes.
- Three models were used to analyze the data, with adjustments made for factors such as age, sex, ethnicity, photo period, employment, physical activity, and shift work.
- The results of the three models were very similar, indicating that the adjustments did not significantly affect the outcomes.
- The odds ratio was used to compare the probability of psychiatric challenges in different quartiles of light exposure.
- The study suggests that there may be less dependency on the adjusted variables, but further questions remain.

- The probability of having worse major depressive symptoms increases as nighttime light exposure increases.
- Bipolar symptoms worsen with nighttime light exposure, especially in the fourth quartile.
- Light exposure at night is especially problematic for individuals with bipolar disorder, independent of sunlight exposure during the day.
- PTSD symptoms and self-harm increase with increasing light exposure at night.
- Daytime light exposure, particularly from sunlight, generally reduces the probability and severity of symptoms for major depressive disorder, generalized anxiety, bipolar symptoms, PTSD, and self-harm.

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