Nutrition Research, Ancel Keys, and the Minnesota Starvation Experiment

Welcome back! I’m Sarah…

… and I’m Becca and you’re listening to Dietetics After Dark! 

S: Today’s episode is going to be jam-packed - Becca is will start off by telling us about nutrition research and covering some of the challenges and ethical considerations that scientists have to make when conducting nutrition research and then we’ll cover the infamous Minnesota starvation experiment that helped us understand the physiology of starvation and still has huge clinical implications today. Anything you want to chat about before we dive in? 

To start off this episode I am going to tell you a little bit about nutrition research in general, and some common issues that have either previously occurred or that currently occur when it comes to studies around dietetics; and then why it is important to understand where this data is coming from.

Now we are so used to being bombarded with headlines about nutrition, but nutrition science is still fairly young. The first vitamin (which was thiamine) was isolated and defined in 1926 - less than 100 years ago. And a lot of the initial nutrition research was around singular nutrient deficiencies like scurvy. Studies looking at how nutrition impacts chronic disease, like heart disease or cancer, are even more recent, having really only taken off in the past 30-40 years (Mozaffarian, Rosenberg & Uauy, 2018). And this can be somewhat frustrating, for sure, since guidelines and best practices continue to change as new evidence becomes available. But it is important that our practices as future healthcare professionals, and just humans in general, continues to be updated as our understanding of things evolves. This is one of the reasons I love dietetics so much. There is still a lot to uncover and learn, and it is never boring.

There are many different ways you can obtain nutrition data, but what is deemed the gold standard in forming causal relationships are Randomized Control Trials. These are where participants are randomly assigned to one of two groups - either the experimental group that receives the intervention, or the comparison group that receives an alternative or control intervention (which sometimes means no intervention at all). These are on the top of the research hierarchy since exposure to the nutrition therapy is completely random here. The participants don’t know which group they are in, therefore bias is often lower and the results are more reliable. 

However, randomized control trials are not always ethical. For instance, the participants aren’t always able to give proper consent to treatment since they are unaware of what treatment they are being given. Therefore you cannot put either of the groups at any known risk. So, for example, if we are conducting a study on the effects of gluten in individuals with celiac disease, we can’t give one group a gluten-free diet and the other group a diet with gluten since the harmful effects of gluten on these individuals is well known and documented. So doing this would be unethical.  (OR the effects of parachutes on sky divers).

Because of these ethical considerations there are some flaws that currently exist in nutrition research...and it can be really tricky to establish causal relationships between certain things. Oftentimes nutrition research will rely on self-reported data like food journals or questionnaires. This type of data will often look at things that can’t be measured using biomarkers, or that would be incredibly expensive to assess through observation - so things like food intake over time, food behaviours, and eating patterns. 

This might present some issues since participants may falsify results for a variety of reasons (like to make their answers sound more “socially acceptable”). They may not interpret the questions as they are intended to be interpreted, or they may not remember the details of what is being asked of them (Subar et al., 2015). There is even a phenomenon called the “White Coat Effect”, which is where the presence of a physician or researcher increases one’s blood pressure. So even just having participants in a research environment or waiting room may impact your results through your participants mood or anxieties.

But self-reported data can also be incredibly useful. It was actually the self-reported data of pregnant women that demonstrated the initial association between folic acid intake and neural tube defects. This was later tested and a causal relationship was found, but it started with women reporting their intake and birth outcomes (Subar et al., 2015). So despite its flaws, this type of research has many more benefits. But it is just good to question headlines that say things like “red wine decreases heart disease”. And ask yourself was a causal relationship made? Or did the researchers look at self-reported data on wine consumption and follow-up with participants at certain points to assess health outcomes?

It can also be incredibly difficult to isolate a single ingredient or nutrient from a food or from one’s diet to be able to find a cause/effect relationship in the body. This isolation likely has to happen in a petri dish, and in reality, there are MANY other factors that come into play with everything that we eat. For instance, we know that antioxidants can help delay the oxidation of cells, but there is little evidence that an antioxidant supplement will have the same health effects as foods with antioxidants. This is likely because other substances in these whole foods increase the effectiveness and benefits of the antioxidants (U.S. Department of Health and Human Services, 2013). And the same goes for fat soluble vitamins - they are better absorbed when combined with fat. So a lot of the things we eat rely on other things to help with transport and absorption - so it’s incredibly complicated.

Lastly, one other thing to consider in nutrition research is that many preliminary studies are conducted on animals. Now the results of things like rodent studies can be incredibly beneficial to establish, but before the same tests are conducted on humans, we should question them a little bit. Like would the same test setting and factors even be applicable to humans? It also leaves out a huge qualitative component that is important in human research, and that is how we feel when certain things happen. Like does our stomach hurt? Or did we get a headache? (Baker, 2008). These things are more difficult to measure in animal studies.

But one of many benefits to animal studies is that compliance is easier with animals than with humans, if you can believe it. There is also a lot of information about human health that we wouldn’t have without animal tests - such as some of the preliminary research around energetics, carbs, lipids, proteins, body composition and growth (Baker, 2008).

This whole intro isn’t to tell you that you shouldn’t trust nutrition research, because it truly is incredible what we have been able to find out so far. BUT you should evaluate where the information in the news is coming from. As we have discussed before, news headlines will often take the results of a study and spin it to sound like fact, when really more information is needed to establish a cause/effect relationship.

Content warning: We talk about hunger and starvation in the context of World War II and the Minnesota Starvation Experiment. There will be some details about calories and weight loss, so if that doesn’t feel like something you’d like to listen to today, then feel free to click off and go explore any of our other episodes! 

Shoutout to my main three sources for this story! I used an amazing book by Todd Tucker called The great starvation experiment: Ancel Keys and the men who starved for science, a journal article called They Starved So that Others Be Better Fed: Remembering Ancel Keys and the Minnesota Experiment by Leah Kalm and Richard Semba, and an article from Medium called What a 1944 Starvation Experiment Reveals About 2020 Food Insecurity by Kelsey Miller, all linked in our show notes. 

S: To set the stage for this story, I need to take you back to one of the most devastating time periods in recent human history, 1941-1945 aka World War II. Throughout the war, hunger was used as a weapon, and cities and countries around Europe experienced extreme man-made famine conditions mostly due to German blockades that cut off the food supply to major cities. Two famous examples that I’m going to very briefly discuss because they are really terrible are the Siege of Leningrad and the Dutch Famine or the Hongerwinter. Leningrad was a city of 3.5 million in the Soviet Union, today it goes by the name St. Petersburg in Russia. The Siege of Leningrad lasted 872 days, starting in September of 1941. Supplies were extremely limited and highly restrictive rations were implemented almost immediately, but even with rations, the death toll was between 1.1 and 1.3 million people. The starvation experienced was extreme - reports from Leningrad indicate that as the food supply dwindled, civilians survived by first eating pets and birds, then making soups out of leather belts and book bindings and wall paper because potato starch was used in the wall paper, and murder rates spiked as people murdered others for ration cards and, yes, some people were forced to resort to cannibalism. 

The Dutch Famine or the Hongerwinter took place over the winter of 1944-1945, again, because of a German blockade that cut off food and farm supply shipments. Again, absolutely devastating effects but not quite as severe as Leningrad because the duration was shorter. What’s interesting about the Hongerwinter is that it took place in a developed country the Netherlands) and so it was well-documented, and it actually played a role in helping to measure the effects of famine on human health. There was a famous study called the Dutch Famine Birth Cohort Study that found that the children of women who were pregnant during the famine were more susceptible to diabetes, obesity, cardiovascular disease, and other health problems and they were also smaller than average, so there were long-lasting intergenerational effects of famine even in those who weren’t technically alive to experience it!

So by the end of 1944 and early 1945, Allied forces (which includes the US) were beginning to enter these war torn countries and the militaries were encountering all the emaciated, starving civilians from these countries and they needed to know how to help them. This is also occurring at a time when relatively little was known about how to deal with refeeding people who had undergone a severe degree of deprivation. So all of this suffering and death at the hands of hunger was catching the interest of scientists and militaries around the world, including one young physiology professor at the University of Minnesota who also happened to be a consultant to the United States War Department, Ancel Keys. Ancel had two main questions 1) how are civilians affected physiologically and psychologically by extremely limited diets and 2) what would be the most effective way to provide rehabilitation after the war? To answer these questions, Ancel proposed a bold human experiment that would subject a group of 36 healthy young men to a 6-month period of semistarvation and then rehabilitate them. 

Before I dive in to the story, I want to tell you more about Ancel Keys because I knew about him in relation to this experiment but I didn’t know the significance of the contributions that Ancel Keys made to not only nutrition science, but also physiology, biology, anthropometry, epidemiology, and even ichthyology. Do you know what that is? 

Ancel Keys lived 100 years, he was born in 1904 and died in 2004, and throughout his life he made major contributions to nutrition science and public health. As a kid and a teen, he was very busy and always trying new things. He had a series of unusual jobs, including cleaning bat guano aka. Poop out of desert caves in Arizona, and working as an oiler on a ship bound for Shanghai, Manila, and Hong Kong. He then completed an undergraduate degree in economics and political sciences, then he got a Masters degree in Zoology, then he got a PhD in oceanography, and then a second PhD in physiology. Some of his major contributions to science included studying adaptation to high altitudes, uncovering the link between serum cholesterol and heart disease, coordinating the first multi-country epidemiological longitudinal study in nutrition and health (SCS), he promoted the Mediterranean diet for a healthy lifestyle, and he developed the K ration to feed the US military during WWII with energy dense but physically light food, and, of course, he formed the foundation for our understanding of the physiology of starvation. 

Let’s talk about those last two. First, the K ration. During the war, Dr. Ancel keys was asked by the US War Department to come up with a light-weight but energy-dense non-perishable meal that could be used as an emergency ration for troops. So Ancel developed the K-ration contained about 2,842 calories and 79g of protein and included breakfast, lunch, and dinner. The Breakfast K-ration contained a can of chopped ham and eggs, a dried fruit bar, some biscuits, sugar, and instant coffee, a packet of four cigarettes, water purification tablets, chewing gum, and toilet paper. The lunch K-ration contained a can of processed American cheese and bacon, biscuits, five caramel candies, some sugar, and a salt packet, 4 cigarettes, a book of matches, and a packet of powdered drink (lemon or orange) and some chewing gum. Dinner K-ration contained a can of beef and pork loaf, some biscuits, a 57g sweet chocolate bar, a packet of concentrated broth, toilet paper tissues, four cigarettes, and some chewing gum. The K-ration was designed to be used for short periods of time, as it was not nutritionally adequate to sustain active men over a long period of time, but it was really successful! Legend has it that the K-ration is named after the “K” in keys, because he invented it, but some say the letter K was actually chosen at random to differentiate it from the other rations available at the time. 

After this work with the US military creating the K ration, Ancel was hooked. He really wanted to study nutrition more, especially the physiological effects of starvation on humans. Simultaneously, the US military also had great interest in learning more about starvation, because they were preparing to enter cities in Europe and expecting to encounter emaciated civilians and they wanted to help rehabilitate them. And maybe some people don’t know this, but refeeding someone after a period of deprivation is actually quite precarious - you can’t just give someone a feast and tell them to go to town - because their bodies have been deprived of nutrients for so long that when they eat again they’re electrolyte balance can be completely thrown off and it can be fatal, it’s called refeeding syndrome. And there are long-term effects as well, which we’ll talk about today. So, there was a lot to learn in this area and Ancel proposed his daring starvation experiment and it got approved! 

In the United States in the summer of 1944, healthy young men weren’t exactly in high supply. Most were either preparing to fight in the war or they were overseas fighting in the war, however, there was a group of young men in the Civilian Public Service who were conscientious objectors! Conscientious objectors were young men that did not want to fight in the war, but that doesn’t mean they were cowards. They were exercising their right to refuse to fight on the grounds of freedom of thought, conscience, or religion, and many of them simply refused to kill another person in the name of their country. BUT that didn’t mean that they didn’t want to help their country and do their part, so they would become a conscientious objector, join the Civilian Public Service, and would contribute to the needs on American soil like fire fighting, forest maintenance, and volunteering for medical experiments. This is actually where the term “guinea pig” was first used, to describe Conscientious Objectors in medical experiments. 

So in the summer of 1944, a brochure was sent out featuring 3 children with empty food bowls and the words “Will you starve so that they be better fed?”. Despite the warnings on the brochure that said starvation could pose serious health risks and that the long-term effects were unknown, they received more than 400 applications. Ancel and his team conducted over 100 interviews, and in the end they chose 36 healthy men in their 20s that had been carefully screened for mental and physical toughness. No history of any anxiety or depression, most were in University, they were athletes, they were very well-rounded, stable young men. 

On November 19, 1944, the men moved into a large dormitory-style room located under the University of Minnesota football stadium where they would be living, eating, showering, and essentially doing everything in the same shared spaces for the next 12 months. 

The Study

The first phase of the study was a 3-month control period. Participants were fed approximately 3200kcal per day of a variety of popular foods. This was designed to get the participants to their normal, healthy baseline weight. The second part of the study was the semistarvation period, which began on February 12, 1945, during which the participants were fed about half of their previous caloric intake at approximately 1800 kcal per day. During this phase, the meals were modelled after what victims in war-torn Europe might be eating, so potatoes, turnips, rutabagas, dark bread, and macaroni. Finally, the last 12 weeks of the experiment were considered the rehabilitation phase where participants were assigned 1 of 4 rehabilitation diets that varied based on energy intake and protein and vitamin content. Remember: the primary goal of the experiment was to hopefully find the best way of rehabilitating someone after a prolonged period of starvation. 

Throughout the entire experiment, the men had to imitate regular life, so they were required to maintain an active lifestyle, including working and studying. They were actually allowed to take courses at the University of Minnesota and most did. They were also required to walk or run a minimum of 35km a week. This meant that during the starvation period, they were experiencing a daily deficit of about 1000-1200 cal which was designed to achieve a progressive decrease in weight of about 25% of their body weight throughout the 6-month semistarvation period. The men were also required to work and many got part-time jobs in town or on campus. And at the start of the experiment, participants were also allowed to have unlimited chewing gum (sugar free I assume) and black coffee. 

The men were also subjected to extensive testing throughout the experiment, including body weight and body fat assessments, physical fitness tests on a treadmill, heart size, heart rate, blood volume, hearing, vision, coordination, oxygen consumption, blood samples, and even sperm count. The men also underwent regular intelligence and personality tests from psychologists, and each participant was required to keep a personal journal. 

Ok so in phase 1, the normalization period or control period, the young men were in great spirits as they got to know each other and they felt excited about being able to contribute to the war efforts without actually going to combat and having to kill other people. They had a uniform of blue pants, white shirts, and sturdy walking shoes that distinguished them from others on campus, they were allowed to take university courses, and remember they were selected from hundreds of candidates because of their physical and mental fitness, so they really felt like a sports team, they had a purpose and it was important. Plus, they were well-fed - 3200kcal per day. During this first phase, many participants volunteered at local community centres, participated in local plays and music productions, and explored the city of Minnesota. 

Things start to go downhill pretty quickly during the semistarvation period. The men were given two meals from Monday through Saturday at 8:00 am and 6:00 pm, and one large meal on Sunday’s around 12:45 pm. The goal was that participants would lose about 2.5lbs per week (which is very high for anyone, but it’s also important to remember that these men were starting the experiment already quite lean - they were active, healthy young men at their baseline weight). 

Pretty quickly, the mood changed. Food is a basic human need and hunger hits the brain fast. Think “hangry” x 1000. In the first few weeks, the sense of camaraderie and optimism faded to a grumble. Meal times became tense and emotions were high as each participant coped with the starvation in a different way. Some gobbled down food as quickly as possible and some savoured every morsel which infuriated the other participants. One participant, Samuel Legg, would sit apart from all the other participants and add water to his food and mash it all into a grey paste before eating it, hoping to fill his stomach for longer. 

The odd behaviours continued to manifest. Some started collecting cookbooks and constantly looked at pictures of food, sex dreams completely stopped and were replaced with dreams of feasting and even of cannibalism as the semistarvation period went on. Others couldn’t stand the sight of others eating, it would make them angry! Some would go to the movies and be so distracted by the food around them or in the scenes that they couldn’t follow the plot. The subject's sense of humour and zest for life faded almost completely. The men became more irritable and impatient, more introverted, and less energetic. The participants reported reduced tolerance for the cold and requested extra blankets, and experienced dizziness, hair loss, extreme fatigue, reduced coordination, and even ringing in the ears. Many withdrew from their university classes because they were unable to concentrate. The participants also lost all interest in sex and dating, which they had been doing during the control period. Ancel Keys famously said about this part of the study “starved people cannot be taught democracy” based on what he was observing. Many measurable changes were also observed during this period, including decreased basal metabolic rate (slower metabolism), lower heart rate, loss of body fat and also of muscle mass (especially in subjects who were quite lean to begin with), shrinking of heart size, decrease in blood volume by 10%, decreased muscle strength. 

I’m going to read a quote by one participant, Samuel Legg, that describes a moment where he realized how much the semistarvation was affecting him:

“I was walking along … [with my] buddy … it was deep into the semistarvation, and we were tired … we would look for driveways when we got to a cross street … so we wouldn't have to walk up one step to get from the road to the sidewalk … And so we would walk in the gutter for a while, looking for a driveway. We were tired and weak. And so we were standing at a corner waiting for a light or something, and a kid came along on a bicycle, and he was really moving, pumping away … And I looked at him and said, “Wow, look at that boy. He's really whizzing.” And then I said to myself, “I know where he's going. He's going home for supper. And I'm not.” And then for a very brief, I hope it was brief, moment … I suddenly hated the boy … I hate at this point to tell you this, because it doesn't speak very well for me. But I remember … with … horror that I could feel such a thing. So utterly irrational, but there it was.”

The participants were slowly starting to crumble. Two volunteers broke diet and were excused from the experiment; one stopped at local shops for sundaes and malted milks and then he later stole and ate several raw rutabagas, and the other participant consumed huge amounts of gum and began eating scraps of food from the garbage. Both also suffered severe psychological distress during the semistarvation period, resulting in brief stays in the psychiatric ward of the university hospital. Another participant broke the diet and later suffered complications that prevented his data from being included. Initially the participants were allowed to chew gum, but some of the men began chewing up to 40 packages/d and so that privilege was revoked. Another of the participants was later excluded because his pattern of weight loss was not consistent with the amount of food intake and energy expenditure, and there was concern raised about excessive gum chewing. Overall, 4 participants were excluded during the semistarvation period, bringing the total included in the final study to 32 participants. 

After the first participant “broke”’diet, a buddy system was implemented. Many participants actually enjoyed the buddy system because they were held accountable by their partner, but also because they were becoming physically weaker. One participant, Jasper Garner, describes going to a store with a revolving door and being unable to open it by himself and having to wait for another person to come by and open the door and then scoot in after them. 

The participants were struggling through the semistarvation phase but they knew that they weren’t actually experiencing true starvation or persecution, and they actually felt very safe and they really trusted Ancel Keys. They would regularly have conversations with him about how the study was going and how they were doing, and there were always scientists around monitoring their health. So in follow up interviews, they participants still had an overall positive view of the experience! Regardless, on July 28, 1945, the subjects were happy to see the end of the semi-starvation part, but they quickly realized that the rehabilitation period was not the feast that they had been dreaming of. In fact, it was still very restricted given their activity levels, with some of the groups receiving only 400 extra calories a day, which is still much lower than the control period. Participants were divided into four groups, each receiving increased but restricted amounts of calories, in order to investigate the optimal number of calories for rehabilitation, and further divided into subgroups with protein and vitamin supplements in order to see if this would help rehabilitation. In the end, it was found that the most important factor in rehabilitation was providing adequate energy or kcal, as long as an adequate amount of vitamins and protein were present, the most reliable weight-gain strategy was high caloric intake.

During the rehabilitation phase, one participant, Samuel Legg, had a very interesting experience. His “buddy” had a friend in Minneapolis and they would sometimes visit for dinner, and Legg would go outside to chop wood while everyone else ate and socialized so that he could avoid any temptations to cheat or steal food. It was unclear from the description, but it seems like his buddy was NOT a participant in the study, but maybe a supervisor from the experiment. But anyways, Legg would go cut wood while everyone else ate. This particular day, Legg was feeling very weak. Not only had he undergone months of starvation, but the rehabilitation phase was just as draining and, as luck would have it, Legg was in the lowest energy rehabilitation group (400kcal more than in the semistarvation period). He also had a mangled finger on his left hand from an incident the week before where he had dropped a car on his hand during maintenance and crushed a finger. Doctors had been suspicious of his mental health and questioned if he did it on purpose or not, but Legg insisted it was an accident. 

The difference between the semi-starvation diet and the rehabilitation diet was nearly imperceptible and that was crushingly disappointing to Samuel - he was given two extra slices of bread and extra turnips and cabbage. He was actually continuing to lose weight because with this small addition of food, his body was retaining less fluid. He had been dreaming of food nearly every night and even dreamt of cannibalism one night, but yet he would not give up on this experiment which had become his purpose during the war. So he’s out there cutting wood, feeling weak, and he picks up a new log and spreads his left hand out over it to steady it and without thinking he brings the ax down... and chops off 3 of his fingers. 

Legg was later quoted as saying “I admit to being crazy messed up at the time. I am not ready to say I did it on purpose. I am not ready to say I didn’t”

The study finally ended on October 20, 1945 and participants were able to leave and eat whatever the heck they wanted. Some of the participants had gone from about 150lbs to 100lbs during the duration of the study and the pictures are shocking - they will be on our instagram. Somehow Ancel Keys was able to convince 12 of the participants to stay for another 8 weeks and track them as they went into an unrestricted period of eating. 

One of the most interesting parts of this study is the long-term impacts that semistarvation had on these men and their relationship with food. The participants were released without any instructions about how to eat once they were out in the world beyond being told not to overeat on day 1. Subjects reported strong and insatiable sensations of hunger, even after returning to their pre-experiment body weight, and they all regained more than they lost. One subject was sent to the hospital to have his stomach pumped because he over-ate too much. One participant, Harold Blickenstaff, said that he “couldn’t satisfy his craving for food by filling up his stomach”. Another participant, Jasper Garner, described it as a year-long cavity that needed to be filled. Estimates for full recovery ranged from 2 months to 2 years, but in follow up interviews none of the men believed there were any negative long-term health effects from participating in the study. 

This phenomenon of hyperphagic behaviour aka over eating after a period of deprivation with insatiable hunger and complete disconnect with hunger cues that was seen in the men from the study was also seen in studies across Europe in areas that had experienced famine during the war. 

Unfortunately, because the study ended after the war had ended, the participants weren’t able to contribute to the war relief efforts as much as they had hoped to. The final results of the study were released nearly 5 years later in 1950 as a 2-volume 1385 page book entitled The Biology of Human Starvation. It was the first comprehensive record of the physiological and psychological effects of starvation and refeeding, and to this day, it remains the most comprehensive scientific examination of the effects of starvation. Given the modern ethical restrictions on this type of study, it is unlikely that such a study will ever be reproduced, but luckily the work contains all the raw data of the experiment, so any researcher could use the data. At the time, in 1950, this was NOT common practice and Keys actually did something pretty groundbreaking because he clearly stated that “The Tables of measurements provide detailed data which might be used by other investigators for further analysis.” and this is now a common practice, so he was a bit of a trailblazer there. 

One thing I want to highlight from this story is that by the standards of many mainstream diets, 1800 kcal (the semistarvation diet for these men) doesn’t seem that restrictive but yet it had hugely significant and long-lasting impacts on the mental and physical wellbeing of these previously super healthy young men. Not just feelings of hunger, but changes in temperament and personality and the development of food obsession and these were men that had no history of anxiety or depression, no history of deprivation of any sort, and yet they were profoundly impacted long term. And in our society, it’s common to see people in the media, especially social media, but also in real life (friends, family), talking about weight loss or new diets, and I hope this story illustrated that severe calorie restriction is no joke - it is extremely difficult and can have long-term impacts on your relationship with food. So - if weight loss is one of your personal goals right now, see a registered dietitian that can help you make sustainable changes.

And that is it for Ancel Keys and the Minnesota Starvation Experiment! 

Question - I know you like coffee, but would you put it up your butt? 

NO WAY!