My answer has always been: “Exercise.” It hasn’t always been a popular answer though.
Physical exercise is beneficial for the body and the mind. A recent (2015) report of the Academy of Medical Royal Colleges highlighted that regular exercise (30 minutes/day, 5 days/week) reduces the risk of breast cancer (by ~25%), bowel cancer (~45%), dementia (~30%), stroke (~30%), and heart disease (~40%). These are remarkable effects – no drug could achieve this across such a spectrum of diseases. Exercise is a powerful medicine.
Exercising your body will help keep your brain fit. This is a known. Another known, from laboratory studies at least, is that caloric restriction (mild starvation but with adequate nutrition) is good for the brain and longevity. This is true across species. Weight stabilises even with caloric restriction because the body adapts its basal metabolic rate. However, such a strategy is not appealing to most humans (including me), especially in our age of abundance.
It is thought that it is not so much the calorie restriction per se, but rather the increase in ketones that calorie restriction causes, that underlies the benefits of such a diet. The high-fat low-carbohydrate ketogenic diet also raises ketone levels, and so may confer similar results to calorie restriction.
So now, the answer I give to that question is: “Exercise, and a ketogenic diet.”
Lets see what a ketogenic diet (KD) might do for the brain. I will concentrate on two disorders: Epilepsy (in which a KD is an established therapy) and Alzheimer’s disease (in which a KD might be a therapy and our high-carbohydrate diet a contributing cause).
It has been known for centuries that fasting can reduce the frequency of seizures in epilepsy (Hippocrates even mentions it). But, this is not a practical long-term strategy. Around the 1920s, doctors noticed that seizures remained under control when they broke the fast with fats, but that seizures rapidly returned when the fast was broken with carbohydrates. Indeed, seizures can return within an hour of injecting glucose. This led to the idea of a high-fat low-carbohydrate (HFLC) diet for seizure control in epilepsy.
The use of a HFLC diet to mimic fasting in epilepsy was suggested by Dr Russell Wilder in 1921. He was the first to coin the term KD, since blood ketones rise both with fasting and with HFLC eating. In its earliest form it was a severely restricted glucose diet, usually preceded by a period of fasting: 90% of calories from fat, 8% from protein, and 2% from carbohydrates. A diet such as this needs to be administered under medical supervision. This is a therapeutic KD. The diet I have been discussing so far on 6XC is a nutritional KD that induces mild ketosis in a safe and sustainable way.
The therapeutic KD turned out to be highly effective, and it became widely administered because, at the time, drug options were limited and not very effective (bromine, phenobarbital). Real progress had to await the development of animal models of epilepsy in the 1930s, which could be used to trial anti-epileptic drugs (AEDs). This led to the discovery of phenytoin (Dilantin) which was effective for a variety of seizures. With this, and subsequently developed drugs, medication became the treatment of choice and the KD was sidelined, mainly because of the challenges the diet imposed (pills were easier, and more in keeping with the medical model).
However, many epileptics remain treatment-resistant or develop complications. This has led to a recent resurgence of interest in the KD as a treatment option. Remarkably, a KD can be effective in drug-resistant epilepsy, attesting to its powerful effect (about a third of drug-resistant epileptics can expect a 90% reduction in seizures). Furthermore, seizures can sometimes remain under control even after the diet is terminated, which means the diet may have modified the disease itself not just the symptoms (something that no AED can do).
How a KD reduces seizures is not fully understood. The KD may reduce neuronal excitability or alter the levels of excitatory and inhibitory neurotransmitters, or be multifactorial. There is interest in better understanding the mechanisms, as this could lead to the development of new and novel AEDs. Meanwhile, its success in epilepsy is definitive evidence that a KD can alter brain function, in this case profoundly.
The cause and mechanisms of Alzheimer’s disease (AD) are not yet certain. One thought-provoking possibility, from a public health perspective, is that AD might be a metabolic disorder. That is, a disorder of energy (glucose) metabolism, perhaps brought on by high carbohydrate consumption.
As a metabolic disorder, there is evidence to suggest that AD combines aspects of type 1 diabetes (insulin deficiency) and type 2 diabetes (insulin resistance). Some researchers are sufficiently convinced to propose that AD be renamed type 3 diabetes, however this is not a majority view. Even if insulin/glucose dysfunction is not the primary cause of AD, there is strong evidence that glucose utilisation in the brain begins to decline early in AD (decades before clinical signs), and it is likely to contribute to the progression of symptoms.
1. Insulin deficiency. It was not until 1978 that insulin was even known to be in the brain. It is now recognised that brain insulin performs many critical functions – some of which are: cell growth and survival; neurotransmitter synthesis (neuronal signalling molecules); synaptogenesis (new connections between neurones, important for memory and learning); brain cholesterol synthesis (cholesterol is crucial for healthy brain function). In the metabolic model of AD, insulin levels decline with the development of insulin resistance.
2. Insulin resistance. Under normal conditions, the brain is dependent on glucose for energy. This makes the brain vulnerable if glucose metabolism becomes dysfunctional. Whether this could arise from high dietary glucose is not known, however, diabetes (and obesity) are risk-factors for AD. In time, dysfunction in glucose metabolism in some brain cells becomes entwined with a developing insulin-resistance in a spiralling and self-reinforcing cascade. This limits glucose transport into the cells, and as well, cells lose their ability to oxidise glucose for energy in the normal way. With progressive decline in energy there is increased inflammation and oxidative stress. Finally, cells sense they are at a tipping point, and kill themselves by a pre-programmed process called apoptosis to minimise damaging nearby cells with their inflammatory and oxidative waste.
Reducing the brain’s dependence on glucose may circumvent some of these problems. However, fatty-acids and amino acids are not realistic alternative fuels because their entry into the brain is regulated by the blood-brain barrier (BBB) – mostly essential fatty acids and amino acids (that the brain cannot synthesise itself) cross in any great numbers. Ketones, however, will easily cross the BBB, and in a dose-dependent way – the more ketones there are in the blood, the more that will cross into the brain. The brain can readily use ketones for energy – ketones bypass insulin resistance. Furthermore, ketones are messenger molecules that up-regulate systems to reduce oxidative stress and inflammation. They are neuro-protective. A keto-adapted metabolism arising from a KD might help rescue stressed brain cells, or be protective for healthy ones.
Little is known of the role, if any, of ketones on the availability of insulin in the brain (the type 1 problem). However, insulin levels might improve with improving cellular metabolism.
The brain won’t be too surprised to find itself being fed ketones, because that’s what it started out with. The developing brain of a foetus and the brain of a new-born breast-feeding infant are keto-adapted. The switch to glucose occurs with weaning, as high-fat mothers’ milk is steadily withdrawn and replaced with low-fat high-carbohydrate food, by convention. At that point the infant brain becomes gluco-adapted and, under normal circumstances, presumably stays that way for life.
Research into KDs in AD is in its infancy – most of what we know about ketones and AD comes from laboratory studies. In an interesting case study (one patient), ketones were administered orally to a person with advanced AD to raise ketone levels above what a KD could reach. There were improvements of memory, cognition and function, none of which could be achieved by conventional medication. It remains to be seen whether this can be replicated.
I have chosen to focus on the metabolic hypothesis of AD because of its clear relevance to diet, however, this is not the only model of AD. Other mechanisms being explored (often in combination) include genetic, mitochondrial dysfunction (the power generators in the cell), inflammation, non-neuronal mechanisms (microglia), protein abnormalities, and reduced availability of fatty acids and cholesterol (from our low fat diet and use of statins). For nearly all of these, a case could be made for also administering a KD.
Considerations supporting a metabolic model for AD include:
- Glucose utilisation is abnormal early in AD and throughout its progression.
- The incidence of AD has increased as our high-carbohydrate low-fat diet became established, and our diet is now higher in glucose than it has ever been historically.
- Plausible mechanisms have been identified.
- A known metabolic disorder, diabetes, is a risk-factor for AD.
Considerations supporting a role for a KD in AD include:
- Ketones are an alternative and efficient fuel for the brain.
- They bypass problems in glucose metabolism.
- Ketones are neuroprotective and anti-inflammatory.
- They were our brain fuel in infancy.
- A KD can improve diabetes (risk-factor) and other health markers.
Other brain disorders
There is increasing interest for a KD in other neurodegenerative disorders such as Parkinson’s disease (PD) and motor neurone disease. PD and AD have some commonalities despite differences in symptoms (which arise from disorders of differing neurotransmitter networks). A KD may be effective in some brain cancers (my post for cancer here). There is developing interest in KDs’ protective role in stroke and traumatic brain injury (TBI), including in recovery. It has been applied or proposed in multiple sclerosis, pain, mitochondrial disorders, depression, mild cognitive impairment, behavioural disorders, Huntington’s disease… The list keeps getting longer. This is the early exploratory phase that science goes through. Nothing is certain yet. The role of a KD in these conditions will take time to determine. That a KD is being so widely investigated by science points to its potential significance.
Meanwhile, a KD may be neuroprotective for people without a neurological disorder, and has benefits that go beyond the brain and address other serious health issues (such as diabetes and obesity). An intriguing observation is that those who have success with a KD frequently take on a more cheerful mood and report a new ‘clarity of thought’, both of which are functions of the brain.
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For more information, visit my KETO-DIET Page
While the research for this post came from multiple sources, the following articles give a good detailed overview of KDs and the brain.
Gassier et al., (2006) Neuroprotective and disease modifying effects of the ketogenic diet.
Ruskin et al., (2012) The nervous system and metabolic dysregulation: Emerging evidence converges on ketogenic diet therapy.
Beds et al., (2015) Aberrant insulin signalling in Alzheimer’s disease: current knowledge.
Acevedo de Lima et al., (2014) Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy