Journal Club with Dr. Peter Attia | Effects of Light & Dark on Mental Health & Treatments for Cancer
- Guest
- Dr. Peter Attia
- Read time
- ~5 min
- Uploaded
- 22 Jan 2024
- Duration
- 3:08:31
- Views
- 246.7K
KEYPOINTS
- 01
Bright days and dark nights are linked to better mental health in 86,000 people
Huberman presents a Nature Mental Health paper that used wrist light sensors on roughly 86,000 UK Biobank participants. It builds on an earlier study of 400,000 Biobank participants linking outdoor time to better mood and sleep. The authors conclude that avoiding light at night and seeking light during the day may be a simple, effective non-drug way to broadly improve mental health. Huberman criticizes the title, which makes it sound as if light itself is harmful.
- 02
Night light showed a dose-response with depression, self-harm and PTSD
Against the quartile with the least night light, the depression risk rose to almost 20% higher in the third quartile and about 25% higher in the fourth. Self-harm was flat across the first three quartiles, then jumped about 30% in the top one. The highest daytime-light quartile had about a 20% lower risk of depression. The associations held largely independent of sleep duration and exercise. Attia singled out the links between night light and PTSD and between daytime light and psychosis, and found anxiety and bipolar results less striking.
- 03
In bipolar disorder, night light looked harmful even with plenty of daytime light
The authors emphasize that for bipolar symptoms, light at night appeared especially problematic regardless of how much daytime light people got. Huberman ties this to ICU psychosis: non-psychotic patients in windowless, constantly lit, noisy units can develop psychosis that clears once they go home.
- 04
The mechanism runs through melanopsin cells wired to mood centers
Intrinsically photosensitive retinal ganglion cells signal the circadian clock and, one synapse away, the habenula and other mood areas. They sit mostly in the lower two-thirds of the retina, so they sample light from above. They add up photons over time rather than switching on instantly. Huberman credits David Berson at Brown for showing these cells can fire for hours under bright light.
- 05
Indoor light is far dimmer than it seems
Huberman says a bright indoor space is about 4,000 to 6,000 lux, while noon sun is over 100,000 and can reach 300,000. An overcast day can still beat indoors. Light through a window you can't see the sun through is largely filtered, skylights help, and glasses or contacts are fine while sunglasses cut a lot. He notes people now spend about 90% of their daytime indoors.
- 06
Low-sun light sets the clock and midday light lifts mood
Color-opponent cells compare blue with yellow and orange at sunrise and sunset. Morning light advances the clock and evening light delays it, and the two balance. Midday is a circadian dead zone for shifting the clock, but bright light then still boosts mood. If you can only manage one, choose morning. If you miss a day, get roughly twice as much the next morning, because the system averages over two to three days.
- 07
Most solid tumors are visible to the immune system but evade it
Attia says lung, breast, prostate, colorectal and pancreatic cancers cause more than half of US cancer deaths, and at least 80% of solid tumors make antigens the immune system recognizes. They escape by secreting suppressors such as IL-10 and TGF-beta and by heavy glycolysis (the Warburg effect), which may serve cell building blocks per a 2009 paper by Vander Heiden, Thompson and Cantley, and acidify their surroundings to repel immune cells.
- 08
Checkpoint inhibitors take the brakes off T cells
CTLA-4 on T cells acts as a brake after antigen recognition. Earlier, high-dose interleukin-2 added gas, helping only about 10% of patients with melanoma or kidney cancer. Blocking CTLA-4 (ipilimumab) or PD-1 (pembrolizumab) removes the brake. The discoverers of these checkpoints won a Nobel Prize, which Attia believes is the only one for immunotherapy.
EXAMPLES
- 01
The ipilimumab phase 3 trial in metastatic melanoma
Patients had run out of standard options. They were randomized 3:1:1 to ipilimumab plus a gp100 peptide vaccine, ipilimumab alone, or gp100 alone, so about 80% got the drug. Median survival was about 10 months on either ipilimumab arm versus 6.4 months on gp100. Roughly 20% of treated patients were alive at about 56 months, while essentially all controls had died by about 44 months.
- 02
Median survival versus overall survival
Attia argues that treatments have extended median survival for metastatic solid cancers, but the long-term cure rate is still essentially 0%, as in 1970. Exceptions include testicular cancer and GIST. He criticizes drugs that cost $50,000 to $100,000 for weeks of benefit, citing a pancreatic cancer drug that added days.
- 03
Side effects track the mechanism
Nearly everyone in all arms had some adverse event, and grade 4 events were similar (about 6 to 8%), likely reflecting the advanced disease. Immune-related events were about 60% on ipilimumab versus about 30% on gp100, with grade 3 to 4 events in 10 to 15% versus 3%. These included colitis severe enough to need IV fluids, rashes and vitiligo. Attia once co-wrote a paper suggesting autoimmunity predicts response, and wished this trial had tested that. He also notes weight-based dosing (3 mg/kg) means men get larger doses, which may explain sex differences.
- 04
A Lynch syndrome patient cured, and left without a pancreas
Attia's friend with Lynch syndrome survived colon cancer, then developed unresectable pancreatic cancer about five years later. Because mismatch-repair defects create many mutations, he joined a pembrolizumab trial. His cancer vanished and he is cancer-free about 10 years later, but his immune system also destroyed his pancreas, leaving him insulin-dependent. Melanoma and kidney cancer responded early for a similar reason: high mutation counts.
- 05
Rick Rubin's red bulbs
While staying in Attia's guest house, Rubin replaced every bulb with red light, and Attia later took the bulbs home. Huberman notes cheap red bulbs work. Attia has softened on blue light: what he does on his phone at night, like doomscrolling or email, matters more to him than screen brightness.
OTHER RELEVANT
- 01
Huberman's four light habits
See low-angle sun in the morning and again in the late afternoon or evening; the sun doesn't need to cross the horizon. Get as much bright light as you safely can through the day; midday sunglasses are fine, but blink and don't stare. Keep nights dim but not pitch black, so you don't trip. Huberman says evening sunlight can halve melatonin suppression from later artificial light, citing a Scientific Reports study.
- 02
Read the study, not the headline
Attia's journal-club tips: redraw confusing figures with arrows, check whether error bars cross the 1.0 line (an odds ratio of 0.7 means about 30% lower odds), and expect large samples to give tight error bars. Remember that observational light data can't rule out reverse causality or a Hawthorne effect from wearing a sensor.
- 03
For hospitalized loved ones, get them near a window
Huberman's standard advice when people with a relative in the hospital contact him: get them near a window and protect their sleep-wake cycle as much as possible, given ICU psychosis.