The ketogenic diet, a high-fat, very-low-carbohydrate diet, has gained popularity for its potential benefits beyond weight loss. Originally developed in 1921 to treat epileptic children, it's now being explored for its impact on various neurological conditions, including traumatic brain injury (TBI), Alzheimer's disease, and Parkinson's disease. This article delves into the potential benefits and risks of the ketogenic diet on brain health, drawing on available research and expert opinions.
How the Ketogenic Diet Works
When you consume foods that contain lots of carbohydrates, the body converts those them into glucose, or blood sugar, which it then uses for energy. On a ketogenic diet, the goal is to restrict the carbohydrate intake so that the body breaks down fat for energy. The ketogenic diet requires you to achieve a state of ketosis. To achieve and maintain ketosis, you have to severely reduce the number of carbs you eat. When this happens, fat is broken down in the liver, producing ketones, which is a by-product of the metabolism. These ketones are used to fuel the body in the place of glucose.
Potential Benefits of Ketones for the Brain
Ketones produced from fatty acids are burned differently than glucose. Ketones are a neuroprotective antioxidant. Ketones increase mitochondrial efficiency and production. The ketogenic diet causes an upregulation of mitochondrial genes and genes utilized in metabolism while stimulating the increase mitochondrial mass.
- Neuroprotection: Ketones are more than 25 percent more efficient than glucose as a fuel source. They actually help to lower free radical production, first by improving mitochondrial function (the battery of your cell that gives you energy) and then by reducing free radical damage. What this means is that ketones can help spare neurons, or nerve cells, from further damage from free radicals.
- Improved Cognitive Function: A study completed in 2012 found that children with epilepsy following a ketogenic diet had improved alertness and cognitive functioning when compared to traditional anti-epileptic pharmacotherapeutics.
- Alternative Fuel Source: Under normal physiological conditions, the brain’s energy supply is mainly covered by glucose. The brain can utilise ketone bodies (KB), such as β-hydroxybutyrate (BHB) and acetoacetate (AcAc), as alternative cerebral energy substrates, supplying up to 60% of the basal cerebral energy requirements.
Ketogenic Diet and Brain Injury
Following a brain injury there is a cellular energy crisis with increased energy needs in the brain. At that same time, the injury impairs the brains ability to use glucose. This results in an energy crisis that causes secondary injury to the brain. Because TBI results in impaired glucose uptake by the brain; providing an alternate energy source such as ketones maybe beneficial. Moreover, ketones are more than 25 percent more efficient than glucose as a fuel source.
Animal studies have shown that increasing KB metabolism through fasting or diet-induced ketosis promotes brain resistance to stress and injury and attenuates acute cerebral injury.
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Clinical Studies on Ketogenic Diet and Brain Injury
Research with the KD in ABI is still in its early stages.
- Arora et al.: Ten patients with acute TBI and ventriculostomy catheter to monitor intracranial pressure were included in the study. The primary feasibility outcome was the achievement of ketosis, and the secondary outcomes were adverse effects related to the KD. Eight out of 10 patients achieved ketosis, blood glucose (BG) decreased in most patients, two patients developed hypertriglyceridaemia, one patient developed hypoglycaemia, and no other adverse effects were noted.
- White et al.: White et al. investigated feasibility and safety by administrating ketogenic enteral nutrition for 6 days to 20 mechanically ventilated critically ill patients with acute ABI, included within 48 h of admission to ICU. The primary endpoint was to investigate the possibility of inducing ketosis using ketogenic enteral nutrition, measured as BHB and AcAc concentration in plasma and cerebrospinal fluid (CSF). Secondary endpoints were to determine the effect of a KD on intracranial pressure, cerebral perfusion pressure, and metabolic and acid-base parameters. Patients were continuously monitored for any adverse effects.
- Bernini et al.: Bernini et al. used cerebral microdialysis to measure levels of BHB and AcAc interstitially in the brain of 34 patients with acute TBI, measured in a fasted state, and by half and full enteral nutrition, either with standard enteral nutrition or with enteral nutrition supplemented with MCT. They found that KB levels in the blood correlated with levels in the brain and that the onset of nutrition was associated with a significant gradual decrease in KB levels both in the blood and in the brain. Nutrition with added MCT did not increase KB in the blood but did significantly increase plasma-free C8 and C10, as well as a significant increase in C8 and C10 in the brain. Levels of KB interstitially in the brain during the fasting acute phase of TBI were associated with increasing age, and Bernini et al.
- Ritter et al.: Ritter et al. randomised 20 patients with acute TBI to either enteral nutrition without carbohydrate and with 175 g fat/L (intervention: nine patients) or enteral nutrition with 141 g carbohydrate/L and 36.8 g fat/L (control: 11 patients). In the control group, the BG level increased whilst remaining unchanged at the fasting level in the intervention group. The intervention group had lower blood lactate concentrations and higher concentrations of KB in the blood. The urine-nitrogen balance was better in the intervention group, receiving a higher protein intake. CSF lactate concentration and cerebral lactate production were not significantly different in the two groups.
- Robertson et al.: Robertson et al. randomised 21 patients in coma after acute TBI, and patients received either glucose i.v. or NaCl (0.45%) i.v. for 5 days. All patients received 3% amino acids (75 g/day), and the control group received 5% glucose (106 g/day). The intervention group got no calories besides protein. There was no difference in blood or CSF glucose concentration in the two groups, but the control group had higher plasma insulin levels. The intervention group had higher blood levels of BHB, AcAc, pyruvate, glycerol, and free fatty acids than the control group. The cerebral oxygen turnover was similar in the two groups, but in the control group, glucose was the only energy substrate for the brain. In the intervention group, BHB and AcAc replaced glucose in 16% of the brain’s total energy turnover. CSF lactate concentration and cerebral lactate production were lower in the intervention group.
MCT-KD in Subacute ABI
No clinical studies investigating the KD in subacute ABI have been published, although there is a solid basis for a hypothesis of a beneficial effect in these patients based on the experimental results. Therefore, a study was designed to investigate if MCT-KD is feasible in adult patients with subacute ABI during a 6-week intervention.
KD prevents the reduction of SIRT1 expression following mTBI
SIRT1 expression within the hippocampus- one-way ANOVA revealed significant between-group differences in SIRT1 expression [F (3,21) = 5.45, p = 0.006, η2 = 0.44]. Gabriel’s post‐hoc analysis showed that the mTBI group had significantly lower SIRT1 levels than the control (p = 0.009), KD (p = 0.038) and mTBI + KD (p = 0.025) groups.
SIRT1 expression within the cortex-one-way ANOVA revealed significant between-group differences in SIRT1 expression [F (3,21) = 6.26, p = 0.003, η2 = 0.47]. Gabriel’s post‐hoc analysis showed that the mTBI group had significantly lower SIRT1 levels than the mTBI + KD group (p = 0.002). In addition, the mTBI group showed a marginally significant trend toward lower SIRT1 levels than the than the control (p = 0.090) and KD (p = 0.077) groups.
Ketogenic Diet prevents mTBI-induced neuronal loss
The number of NeuN + neurons in the cortex and dentate gyrus-one-way ANOVA revealed significant between-group differences in the number of NeuN + neurons both within the cortex [F (3, 16) = 5.06, p = 0.012, η2 = 0.49] and the dentate gyrus [F (3, 16) = 8.51, p = 0.001, η2 = 0.61]. Gabriel’s post‐hoc analysis demonstrated that the total number of NeuN + neurons within the cortex was significantly lower in the mTBI group than in the control (p = 0.018) and mTBI + KD groups (p = 0.028). The total number of NeuN + neurons within the dentate gyrus was significantly lower in the mTBI group than in the control (p = 0.008), KD (p = 0.012), and mTBI + KD (p = 0.002) groups.
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Ketogenic Diet mitigates TBI-induced neuroinflammation by reducing reactive astrocytes
GFAP Intensity in the cortex and dentate gyrus- one-way ANOVA revealed significant between-group differences in GFAP intensity in the dentate gyrus [F (3, 16) = 3.14, p = 0.055, η2 = 0.37], but not in the cortex [F (3, 16) = 2.60, p = 088, η2 = 0.33]. Gabriel’s post‐hoc analysis demonstrated that the GFAP intensity in the dentate gyrus was higher in the mTBI group than in the mTBI + KD group (p = 0.043).
GFAP Morphology in the cortex and dentate gyrus-one-way ANOVA revealed significant between-group differences in GFAP Morphology in the dentate gyrus DGH- [F (3, 16) = 3.28, p = 0.048, η2 = 0.38], but not in the cortex [F (3, 16) = 0.52, p = 0.674, η2 = 0.09]. Gabriel’s post‐hoc analysis revealed marked alterations in astrocyte morphology in the dentate gyrus of mTBI mice versus controls (p = 0.042).
Activated microglia expression in the cortex and dentate gyrus-one-way ANOVA revealed no significant differences between groups in the number of activated microglia within the cortex [F (3, 16) = 2.37, p = 0.108, η2 = 0.31] or dentate gyrus [F (3, 16) = 2.15, p = 0.134, η2 = 0.29].
Other Potential Benefits
There is more to the keto diet than weight loss. It has been shown to help Polycystic ovarian syndrome (PCOS) is an endocrine disorder that causes enlarged ovaries with cysts. There aren't a lot of clinical studies on the ketogenic diet and PCOS. One study followed 5 women over a 24-week period found that the ketogenic diet increased weight loss and assisted in hormone balance.
Risks and Side Effects
It is common for individuals starting the diet to experience flu-like symptoms, like headaches and muscle aches. This side effect is SO common there’s a name for it: keto flu. To counter the keto flu it is recommended staying hydrated and keeping up with your electrolytes by using electrolyte tablets or Pedialyte. Other potential risks include kidney stones, vitamin and mineral deficiencies, and gastrointestinal distress. While some fats are healthy, there’s a risk in following a high-fat diet, you’ll increase your intake of unhealthy trans and saturated fats. These bad fats are found foods like red meat, poultry skin, cheese, and butter. They can lead to an increased risk of bad cholesterol and heart disease.
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Important Considerations
Despite all the positive effects of the ketogenic diet it is not appropriate for everyone, this includes people with kidney disease, or any pre-existing liver, pancreatic or kidney issues or conditions. Some rare conditions such as Muscular Dystrophy and other conditions may complicate and severely distress the pancreas, liver or kidneys. This diet may not be appropriate or safe for people who are pregnant, nursing or who have Gestational Diabetes and for anyone suffering or recovered from an eating disorder. Please check with your doctor or health professional before starting this diet to make sure it is safe and right for you.