ketogenic diet
About 15 years ago, one of the runners in our training group announced that he was going on a carbohydrate free diet. I thought he was mad. Initially, I thought he was just giving up sugar, but when questioned he said he was also giving up rice, potatoes, pasta, bread - basically all carbohydrate. This simply didn't make any sense; it was crazy. Where was he going to get his energy from? How would he be able to run?

Skip forward about seven years, and I started to hear a lot more about low-carb, high-fat diets. It seemed that quite a lot of athletes were adopting this, particularly those in the ultra-running community. Perhaps it wasn't so crazy after all. After doing a bit of research, I came to the conclusion that there may well be benefits, not just for weight loss (which I wasn't interested in) but for improving the immune system and, better still, helping my running. I was keen both to boost my immune system, as repeated coughs and colds had jeopardised training over the years, and keen to avoid hitting the wall in marathons. So, with this in mind, I stuck to a low-carb, high-fat diet for about a year, just to see how things went and how easy or difficult it was. This happened to coincide with a period of plantar fasciitis, which meant I wasn't able to run much, perhaps a good thing as it was quite difficult to stick to the diet even without the complication of competitive training. What I did find was that I was not troubled by coughs or colds for most of that year, and when I did catch a bug at the start of my summer holiday, I recovered much more quickly than normal and was able to do some light running by the end of the week.

In all my research and during my own travels into the world of the low-carb, high-fat diet, the fact that this type of diet might also help those with mental illness had fallen below my radar. So, I was interested to read a case report in the Frontiers of Nutrition this month about three people who had achieved full remission of major depression and generalised anxiety disorder on adopting this diet (ketogenic metabolic therapy).

Psychiatric conditions such as schizophrenia, depression, bipolar disorder and binge eating disorder, are neurometabolic diseases involving glucose hypometabolism, neurotransmitter imbalances, oxidative stress and inflammation. These disturbances can be modified by use of ketogenic metabolic therapy (KMT), otherwise known as a low-carb, high-fat diet. So, what you eat can directly affect how you feel. I think that, at heart, we all know this even if just from eating too many travel sweets on a long car journey and feeling a bit rubbish for the rest of the day.

Insulin resistance in the brain results in glucose hypometabolism and a vicious cycle of unmet energy needs. Unmet energy needs in the brain manifest themselves in cognitive impairment (mental fatigue, memory problems, confusion), emotional symptoms (irritability, anxiety, depression) and physical symptoms (headaches, dizziness, weakness). Although the brain primarily uses glucose for its energy needs, it can adapt to using ketones as an alternative fuel.

In a low-carb, moderate protein, high-fat diet, there is a shift from using glucose to using ketone bodies as the primary fuel source. The ketones provide the brain with a more efficient energy source than glucose and may be exerting other beneficial effects on the brain. Studies have shown that a ketogenic diet improves mitrochondrial metabolism, neurotransmitter function and oxidative stress/inflammation, while also increasing neural network stability and cognitive function.

Low-carb, high-fat diets can be very strict, with the fat to non-fat ratio as high as 4:1. Interestingly, these diets have been shown to have some usefulness in paediatric epilepsy, and reports of this go back as far as the 1920s. But lower fat-to-non-fat ratio diets, which provide more variety, have also been shown to alleviate many mental disorders. There is evidence that they may be effective in schizophrenia, anxiety, autism spectrum disorder, major depressive disorder, binge eating disorder, ADHD and obesity.
keto diet slide information
© Norwitz, Nicholas G.; Sethi, Shebani; et al.Slide from summary of the Norwitz paper
All three cases in the current study involved complex presentations, including major depression, generalised anxiety, other anxiety disorders, and comorbid psychiatric conditions. The subjects underwent a personalised, whole food, animal-based, low-carb, high-fat diet (KMT) for 12-16 weeks. The treatment plan included twice-weekly visits with a dietician, daily photo journaling and regular blood tests. Additionally, they received support through virtual groups and family and friends. The regimen was complemented by nature walks several times a week, as well as community-building activities.

It is difficult to evaluate how much the added extras in the treatment plan contributed to the results - perhaps if people had more time with family and friends, and spent a bit more time out in the countryside, they would feel a lot better too. The effects of exercise on mental wellbeing can't be underestimated. In his book Spark: The Revolutionary New Science of Exercise and the Brain, John Ratley details several case studies involving anxiety, depression, attention deficit disorder and addiction, demonstrating the effectiveness of exercise in these cases. So, the walks in nature are a definite plus in this case. However, this can only partly explain the results, which were quite startling.

In case one, the subject reported "increased mental focus, increase energy, renewed confidence and motivation to return to work. Within four weeks of initiating KMT, he secured a demanding full-time position exceeding his previous experience; after eight weeks, he was given additional responsibilities, handled them well and began three online college courses."

The second case reported "increased mental focus, more patience with co-workers and family and stated he no longer felt a general pull of anger all the time". While, for the third case, complete remission of depression occurred. After a total of eight weeks of consistent nutritional ketosis, she said: "I don't have it anymore. I've just noticed, I'm happy all the time, which is funny."

In this study, the participants were very heavily supported, e.g. they got more than a 5-10 min appointment with their GP and a prescription for anti-depressants. However, the time invested was well spent. When I worked as a community pharmacist, I was shocked by how many anti-depressant prescriptions I was fulfilling. On one occasion, hearing that the price of a popular anti-depressant was about to rise dramatically, I purchased the wholesaler's entire stock. I didn't need to worry that I would end up with out-of-date stock; those hundreds of packets of anti-depressants weren't on the storeroom shelf for long. I felt that there must be something wrong if I was dispensing repeat prescriptions for these drugs; either they work or they don't. The repeat nature of the prescriptions suggested to me that they didn't work. But at the time, I didn't know what the answer was; could something as simple as a change in diet be the solution?

Adopting a low-carb, high-fat diet is not easy. If you go down to the shops on the ground floor of our hospital, you will be hard-pressed to find anything that you can buy for lunch if you are on this kind of diet - perhaps a packet of cheese from M&S, but you can't eat that every day. I found that you had to be super organised (possibly not something that comes naturally to most of us, especially while depressed) and you have to be quite determined, even stubborn, to stick to it in the face of colleagues birthdays ("come on, have a piece of cake"), restaurant visits ("so you want the burger but you not the bun or the fries?") and family meals (the kids don't want to eat that kind of food). It was also more expensive than a normal diet and I found it a little difficult to find the variety of things that I wanted to eat. Maybe I should have done what my husband does and just eat more cheese and nuts, but at that time I was the only member of my family adopting this diet, so I found it quite challenging. If there were a bit more support, as the people in the case studies had, then I think it would be a lot easier for people to stick to the diet and see the benefits. It was notable that at times the subjects of the study required some supplements, e.g. acetyl-L-carnitine, vitamin D and magnesium glycinate, and these additions would not be something everybody would necessarily consider if they adopted this diet without support.

This might not be the solution for everybody. As the authors note: "this case series is limited by describing only three patients, which limits the generalisability of our results as well as the inherent selection bias, as they were interested in KMT after failing standard therapies." Certainly, without support and without the desire to see change, it will be a non-starter. But for those who are determined to beat their mental disorders, it provides a relatively simple, drug free solution.

The "Patient Perspectives" in this paper are well worth reading if you want any encouragement that this can be an effective approach to treating these mental disorders.

Wouldn't it be better for the NHS to invest in good nutrition rather than investing in drugs that clearly aren't working? Major depressive disorder and anxiety are neurometabolic disorders. Doesn't it make sense, then, to treat them with nutrition rather than medication? The NHS might like to start by changing the Eatwell Guidance, where fats are a tiny slither on the chart, instead of >50% of the dietary intake that they probably need to be.
Dr. Maggie Cooper is a pharmacist and research scientist.