Thread by @Willyintheworld

1/ Since chronic diseases & nutrition science are in the news, want to share my fave nutritional experiment: the Minnesota Starvation Experiment.

2/ Context: during WWII, as Allied forces liberated German-occupied Europe, they encountered tons of starving people - but the science of refeeding them was very uncertain. So they did an experiment.

3/ thirty-six male conscientious objectors (volunteers!) were starved to 75% of original body weight over 24 wks, closely observed/measured, & refed back to their original weight.

Ofc, starvation has been very common, esp in war, but actually studying it rigorously - rare!

4/ Prior work had focused on anorexia, or observed patients w/ cancer, certain gastrointestinal disorders, & type 1 diabetes, who had, to varying degrees, some of the features of starvation. The inter-war period also saw a lot of work on specific vitamin deficiencies.

5/ The big contributions of the Minnesota Experiment were 1) how controlled the conditions were; 2) how thorough the physiological and behavioral testing was; 3) tracking the same subjects through both starvation & refeeding

6/ Side note: I love how optimistic and generally experiment/acc the authors are - they're laser-focused on how useful the knowledge gained will be for all of mankind

7/ The volunteers were fully informed of the risks, and ~60 yrs later later the remaining participants, were very proud of having participated. (bioethicists who forget to count this benefit of altruism as a benefit to participants should take note...)

8/ The scientists who designed the experiment wanted to have high "external validity" - they wanted to make sure it was similar to real-world famine conditions - so they used prolonged & moderate caloric deprivation instead of 100% fasting for a few days

9/ BMI of the participants at the start was ~ normal, averaging about 22 (overweight is >25). They worked ~15 hrs/week, classes 25 hrs/week, & had to walk a few miles

10/ In total, there was a 12-week control period where subjects were closely measured, weight was constant, followed by 24 weeks of semi-starvation, and 12 wks of rehab/refeeding; with measurements throughout and also a few months after the experiment ended

11/ Diets were strictly controlled, and in the later stages of the semi-starvation period, a buddy system was instituted so that anytime participants left their rooms, they weren't alone, and couldn't cheat on their diet.

Control diet ~ 3500 cals; semi-starvation ~1600 cals

12/ In the graph below you can see how a drastic cut in calories leads to rapid weight loss among participants, which slows as bodyweight drops & as metabolic rate on a per-weight basis also drops.

13/ in the rehab stage, different "speeds" of refeeding were tested. When subjects were allowed to control their intake, they sometimes reached 7-10k calories per day (!), though generally averaging around 3-4.5k calories per day

14/ Because edema (retention of fluid) can develop with starvation, refeeding can sometimes cause paradoxical weight loss, as the edema resolves with more calories.

15/ More interesting: researchers could predict w/ good accuracy trajectory of particapants' weight loss. Calories in/out vindicated - though note participants in recovery period ended up roughly at pre-starvation weight; so set-point theory is also vindicated!

@sguyenet

@sguyenet 16/ Consequences of the starvation they observed: (--) in body fat; (-) in muscle; (-) heart rate; (-) in blood pressure; (--) drop in motivation, & participants felt much dumber/apathetic, though IQ scores & sensory testing results were *unchanged*

@sguyenet 17/ the neurological results were interesting: sensory acuity was unchanged, reaction time was mostly fine; but motivation takes a huge hit, movement is slow & half-hearted.

@sguyenet 18/ Hearing seems to get *better* during starvation - not sure if we understand why.

@sguyenet 19/ physical performance, unsurprisingly, is hit hard during starvation. Muscular endurance suffers the most, then strength (eg, grip strength), & coordination is only modestly impaired. Recovery took a while: ~30 wks (!) after refeeding commenced for grip strength to normalize

@sguyenet 20/ psychologically, as starvation set in, participants became increasingly irritable, low energy, and obsessed with food. Their libidos dissapeared. Two of the participants (of the original 36) were briefly hospitalized for psychiatric symptoms and left the experiment early.

@sguyenet 21/ None of the participants felt they'd suffered permanent harm from the experience, though it probably took a year or two for their full strength to return. They generally agreed they would "do it again", and were proud of having helped the world.

@sguyenet 22/ Many of the participants went on to very distinguished careers, but still took immense pride in their wartime service. Reminiscient of undirected kidney donors who take satisfication in their donation. @dylanmatt @joshcmorrison

@sguyenet @dylanmatt @joshcmorrison 23/ If you like this thread, recommend checking out Stephn Guyenet's book, The Hungry Brain, for an overview of obesity science. Also check out @KevinH_PhD who does randomized trials on diff types of diets in in-patient (controlled) settings.

@sguyenet @dylanmatt @joshcmorrison @KevinH_PhD 24/ you can find the book (source of most of the images) on Internet Archive; the other study I quote is the June 2005 paper by Leah M. Kalm and Richard D. Semba

25/ my other favorite caloric restriction studies are the CRON cohort & Biosphere 2. Calorie restriction in humans: an update by Fontana et al is a nice overview