DO KETONE SUPPLEMENTS INCREASE BDNF LEVELS?

Ketosis Diet Plan and its Benefits

The ketogenic diet is a high-fat, low-carbohydrate diet that induces a state of ketosis. Ketosis is a metabolic state in which the body burns ketones (i.e., fat for energy), a byproduct of fat breakdown, instead of glucose for energy. Healthy fats ketogenic diet foods include avocado, coconut oil, olive oil, MCT oil salad dressing, butter or ghee, and nuts and seeds (e.g., almonds, walnuts, chia seeds, flaxseeds).

When people think of “ketosis,” they often associate ketogenic diets with losing weight. However, in addition to weight loss, dietary ketosis through low-carb diets and ketone supplements has also been found to positively affect cognitive function. (EVANS & EGAN, 2018; Gyorkos et al., 2019; Jensen et al., 2020)

Ketosis and Neurprotection

In addition to its potential cognitive benefits, ketosis has been proposed to have neuroprotective effects in acute brain injury and various neurological disorders, such as stroke, traumatic brain injury, and multiple sclerosis. (Rusek et al., 2019)  A 2022 study found that the ketogenic diet could counteract neuroinflammation in multiple sclerosis.(Di Majo et al., 2022)

A ketosis diet results in the increase of blood metabolite beta-hydroxybutyrate (BHB). BHB is a type of ketone body produced by the liver when the body is in a state of ketosis. It is an alternative energy source when carbohydrates are unavailable for the heart, muscles, and brain.

Beta-hydroxybutyrate (BHB) has been associated with various health benefits, such as improved cognitive function. This was covered in another article on Evidence Based Muscle. Interestingly, BHB has been found to increase another protein called brain-derived neurotrophic factor (BDNF). BDNF plays a crucial role in neurons’ growth, development, and maintenance, essential for learning and memory.

Exercise and BDNF

BDNF plays a crucial role in neurons’ growth, development, and maintenance, essential for learning and memory. It’s levels can be influenced by various factors such as diet (i.e., reduced carb intake and intermittent fasting diets), exercise, and environmental stimuli. (Phillips, 2017; Scarmeas et al., 2018) A meta-analysis of 29 studies found a moderate effect size for increases in BDNF following a single exercise session. Regular exercise intensified the effect of a session of exercise on BDNF levels.(Szuhany et al., 2015)

The increase in BDNF levels depends on exercise intensity (Marquez et al., 2015). High-intensity and moderate-intensity aerobic exercise can increase BDNF levels, with shorter bouts being more effective and responsiveness varying based on physical fitness and age. (Antunes et al., 2019) Another study found that high-intensity exercise had a significantly greater increase in BDNF levels compared to low-intensity exercise.

Higher levels of BDNF are generally associated with better brain health, cognitive function, and resilience to neurological disorders. Conversely, reduced BDNF levels have been linked to neurodegenerative diseases, such as Alzheimer’s, and mood disorders, like depression.(Zuccato & Cattaneo, 2009)

BDNF Supplements

Research results suggest that several supplements may increase BDNF levels. Omega-3 fatty acids are among the most extensively researched supplements and have shown to elevate BDNF levels in both animal models and humans (Matsuoka et al., 2015). Other supplements, including curcumin, resveratrol, acetyl-L-carnitine, and ginseng, have also demonstrated potential in increasing BDNF levels. Nonetheless, further studies are essential to comprehensively understand their impact on human BDNF levels.

The relationship between ketosis and BDNF Levels

It has been suggested that high-fat, high-calorie, western diets increase Inflammation and oxidative stress and are known to contribute to cognitive decline and neurodegenerative diseases. Some studies suggest that ketosis may have anti-inflammatory and antioxidant effects, potentially explaining its cognitive benefits. (Youm et al., 2015)

While the ketogenic diet has been the primary focus in the literature on ketosis and cognitive function, recent studies have begun to investigate the potential cognitive benefits of exogenous ketone supplements, such as ketone esters and salts. (Stubbs et al., 2017) A ketogenic diet for beginners can cause several unwanted side effects, such as the keto flu in the first few weeks. These supplements can elevate blood ketone levels without following a ketogenic diet, allowing a less stringent dietary approach to achieving ketosis.

In 2016, an animal study found that exercise increases in BHB increased BDNF. (Sleiman et al., 2016) Furthermore, exogenous supplements (i.e., ketone salts and ketone esters) have also been shown to increase BDNF. (Walsh et al., 2020) These findings indicate that ketosis may enhance cognitive function by promoting BDNF expression.

The question is, if a ketogenic diet plan increases BDNF, can following a long-term diet boost BDNF more than someone not following a keto diet? Additionally, does exercise combined with a ketone supplement boost BDNF more than a placebo? These are some of the questions tested in a study in the Journal of Brain Sciences. This study had 3 sections so I will summarize each of the key points of the study.

STUDY 1: How does a ketone supplement affect BDNF in keto-adapted subjects vs. those consuming a mixed Western diet?

Resting ketones were 2-fold higher in the keto-adapted subjects than the mixed diet. The ketogenic supplement resulted in higher ketone levels than water in both groups. The increase in BHB was greater in the keto-adapted participants during and after exercise.

BDNF levels increased after exercise in all groups; however, there were no differences between the keto-adapted and mixed-diet groups.

STUDY 2: How does a keto diet versus a mixed diet impact metabolic and performance outcomes during a 12-week resistance training program?

Insulin was lower in the keto group vs. the mixed diet. Insulin sensitivity was improved in the keto group compared to the mixed diet. The keto diet also lost more weight than the mixed diet. After 12 weeks, BDNF levels did not differ between the ketogenic and mixed diets.

STUDY 3: How does a low-calorie ketogenic diet, with and without daily use of a ketone salt, affect BDNF levels in overweight/obese adults compared to or calorie-controlled low-fat diet?

Both ketogenic diet groups experienced an increase in fasting ketone levels compared to baseline and compared to the low-fat diet group.  Interestingly, BDNF levels decreased throughout the trial in all three groups, with no differences between the groups. Interestingly, the low-fat group had the greatest drop in BDNF (83.4%), followed by the keto diet with no supplement (65.5%), and the keto diet with supplement had the least drop in BDNF (53.4). Again, these changes did not reach statistical significance.

The results of these studies suggest that raising ketosis will not elevate BDNF. (Kackley et al., 2022) All the studies found that ketogenic diets and ketone supplements raised BHB levels, but there were no increases in BDNF compared to the mixed Western diet. It also shows that exercise increases BDNF acutely, but after 12 weeks on a ketogenic diet, there are resting increases in BDNF. A notable finding was that a calorie-restricted diet decreased BDNF regardless of the type of diet followed.

SUMMARY

In conclusion, researchers and health enthusiasts have focused on the ketogenic diet and ketone supplements for their potential cognitive benefits, especially their effect on BDNF. While ketosis increases BHB levels, which many associate with health benefits like enhanced cognitive function, current studies indicate that neither ketosis nor ketone supplements raise BDNF levels significantly more than a mixed Western diet does.

Exercise, however, does acutely increase BDNF levels, but long-term ketogenic diets do not lead to resting increases in BDNF. Interestingly, calorie restriction decreases BDNF levels regardless of the diet type. For now, it is important to consider a holistic approach to brain health that encompasses a balanced diet, exercise, and other lifestyle factors.

REFERENCES

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Di Majo, D., Cacciabaudo, F., Accardi, G., Gambino, G., Giglia, G., Ferraro, G., Candore, G., & Sardo, P. (2022). Ketogenic and Modified Mediterranean Diet as a Tool to Counteract Neuroinflammation in Multiple Sclerosis: Nutritional Suggestions. Nutrients, 14(12), 2384. https://www.mdpi.com/2072-6643/14/12/2384

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