The ketogenic diet: fad or phenomenon?

Danielle Gruber
10 min readOct 4, 2020


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Disclaimer: I am not endorsing nutritional ketosis as a supplement to or replacement for medication. More research is needed to better understand both the potential benefits and side effects of the ketogenic diet (KD).

Would you be surprised if your doctor put you on a diet allowing you to eat an entire block of cream cheese, a pile of crispy bacon, or a nice, juicy, T-bone steak — in order to lose weight? I know I would!

All of these foods and more proudly hold the KD stamp of approval. High in saturated fat and extremely low in carbohydrates, the diet is adopted by a growing number of people to promote weight loss and physical health. Swapping fruit for bacon on your breakfast plate, or sugar for a slab of butter in your coffee, are some of the counterintuitive changes followers of the keto cult make on a daily basis.

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But weight-loss is not the only touted benefit of KD. Versions of the diet have successfully treated drug-resistant epilepsy in children since the 1920s, and emerging evidence suggests it could prove useful for various other diseases, ranging from diabetes to cancer.

How? Why? You may be asking. Well, I’ll tell you.

Ketosis in a nutshell 🥜

Human bodies are typically sugar-driven machines: we ingest carbohydrates, break them down into glucose, and then use this as energy or store it as glycogen in liver and muscle tissue. When carbohydrate supply runs low, the body enters a metabolic state of ketosis, in which fat becomes the primary source of fuel.

Here’s how it works:

  • When your body is deprived of carbohydrates, it eventually burns through glucose (blood sugar) and glycogen stores (stored sugars), and needs an alternative source of fuel.
  • Your body starts to break down dietary and body fat into fatty acids. Your liver converts the fatty acids into ketones, molecules that can be used for fuel.
  • These ketones are released into your bloodstream, taken up by the brain and other organs, shuttled into energy-producing mitochondria, and used up as fuel.
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Ketones to the rescue!

KD has been promoted as a way to treat everything ranging from high blood sugar to inflammation. Here’s why:

  • Ketones provide an alternative energy source when the body and brain cannot use glucose.

Many neurological diseases share one major problem: deficient energy production. For example, insulin resistance — usually developed in older individuals or those with diabetes — makes the body and brain unable to use glucose from your blood for energy. In cases like these, ketones provide an alternative, and possibly more efficient, energy source.

  • Ketones improve your body’s glycemic control.

In diseases such as diabetes, cells can no longer suck up all the tasty glucose in your blood, leaving you with high levels of blood sugar. Because KD can be very effective at lowering blood glucose, it has been used as a method to regulate blood sugar and improve glycemic control.

  • KD increases the number of “energy factories” in your cells, creating greater access to fuel.

A recent study found that KD increased mitochondria volume in liver and skeletal muscle and median lifespan in rats — all without changes in oxidative damage or antioxidant protein levels in the muscle, liver, or brain.

This could have big implications for people who suffer from disorders such as mitochondrial disease, in which mitochondria are unable to completely burn food and oxygen to generate energy.

  • KD may starve off cancer cells dependent on glucose.

There is some evidence that KD may be beneficial after initial cancer therapy due to its anti-tumor effects. Since tumor cells depend on glucose for energy production, it should be possible by means of a KD to selectively “starve them out.”

In normal cells, KD leads to decreased blood glucose and increased ketone-use. Cells must shift from glycolysis to respiration to continue extracting energy. However, cancer cells should be unable to undergo this shift (due to their alterated oxidative phosphorylation) and, therefore, die.

  • Ketones break down oxidants, which can be harmful to protein and membrane structure.

A ketogenic diet may also directly inhibit oxidants — highly reactive oxygen species that are the byproducts of cellular metabolism. Unlike oxygen gas, oxidants have a single electron that increases their tendency to interact with proteins and membranes, often wrecking their structure.

Ketones help break down these violent molecules by increasing the activity of glutathione peroxidase, a part of our innate anti-oxidant system.

  • KD reduces inflammation.

Due to its high fat nature, KD increases poly-unsaturated fatty acids (PUFAs). PUFAs target inflammation by inhibiting the expression of genes encoding for pro-inflammatory factors. Additionally, ketolytic metabolism elevates levels of the neuromodulator adenosine, which has anti-inflammatory properties.

  • KD improves the quality of your gut microbiota.

Your gut microbiota is the collection of microorganisms that dwell inside your digestive tracts. While you may not think much of the community of bacteria, archaea, and fungi living within you, these tiny squatters play a significant role in physiology, metabolism, nutrition, immune function, and even the brain and behavior. Disruption to the gut microbiota has been linked with gastrointestinal conditions such as inflammatory bowel disease and obesity, as well as mental illnesses such as depression.

A study investigating the link between gut microbiota and the anti-seizure effects of KD found that KD modifies the gut microbiota, increasing the putatively beneficial bacteria Akkermansia muciniphila and Parabacteroides spp.

In addition to increasing the good/bad bacteria ratio in your gut, this microbiota transformation (indirectly) increases the GABA/glutamate ratio in the brain. Read the next section to see why that’s important 👇

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The balance-restoring powers of ketones ⚖️

Balance and regulation are essential in the human body. Sixth grade science teaches us about homeostasis, which refers to an organism’s ability to keep a constant internal environment. We usually learn about this in the context of temperature regulation or regulation of the amounts of water and minerals in the body.

But there is another type of regulation that goes on in your brain, one that seeks an optimal balance between excitation and inhibition. This is primarily achieved through two neurotransmitters: the excitatory glutamate and the inhibitory GABA. Tilt the scale towards glutamate — which occurs in stroke, seizures, and neurodegeneration — and you get toxic hyper-activity.

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Studies have indicated that ketones may help restore the excitatory/inhibitory (E/I) balance by

  1. Limiting a neuron’s ability to package and release glutamate for excitatory transmission (decreasing the E), and
  2. Increasing GABA in the synapses, where neurotransmitters are released (increasing the I)

The lab I currently work at, LCNeuro at the University of Stony Brook, has been investigating how diet modulates yet another measure of balance in the brain: brain network stability, which refers to sustained functional communication between brain regions. Check it out!

The fat-fueled brain 🧠

Although research on the link between KD and cognitive function are still limited, several potential benefits have been identified:

  • Memory: A study of 23 older adults at risk of Alzheimer’s disease showed improvement in memory after following a very-low-carb diet for six weeks.
  • Brain function: In one study, older and obese rats fed a KD for three weeks showed improved cognitive performance during T-maze and object recognition tests.
  • Migraine headaches: An observational study of migraine sufferers showed that the KD reduced the frequency and number of headaches.
  • Parkinson’s disease: In a pilot study, five out of seven people with Parkinson’s disease who completed a four-week ketogenic diet experienced a 43% improvement in self-reported symptoms.
  • Amyotrophic Lateral Sclerosis (ALS): In an animal model of ALS, a ketogenic diet led to delayed motor neuron death and histological and functional improvements.
  • Traumatic brain injury: A study of twenty severely head-injured patients showed that those who were fed a carb-free formula were able to obtain nourishment while avoiding high blood sugar, which can hinder recovery.
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Too good to be true?

KD doesn’t come without its fair share of side effects and risks. Take the following into consideration before going keto:

  • The “keto flu”

As your body adapts to its new, carb-deprived state, you may experience symptoms similar to withdrawal, such as irritability and strong cravings for sugar.

Additionally, as your ketone levels increase, your body will try to flush them out through frequent urination. This may lead to dehydration and flu-like symptoms, such as dizziness, fatigue, nausea, and muscle soreness. The inevitable loss of electrolytes can exacerbate these symptoms.

For most people, the keto flu only lasts about a week.

  • Kidney and heart damage

The loss of electrolytes such as sodium, magnesium, and potassium through increased urination can make people prone to acute kidney injury. This may put you at risk of a cardiac arrhythmia, as electrolytes are necessary for the normal beating of the heart.

  • Nutritional concerns

KD is extremely low in certain fruits, vegetables, grains, and legumes that are important sources of fiber, vitamins, minerals, and phytochemicals. Eliminating these nutrient-rich foods from your diet can lead to bone loss and increased risk of chronic diseases.

Hundreds of studies suggest that whole-food, plant-based diets are linked with lower levels of diseases such as type 2 diabetes and heart disease. While you can use keto for health benefits in the short-term, you may want to switch to something like the MIND diet, in the long-term.

  • Other side effects

Other potential side effects of KD include bad breath, fatigue, constipation, irregular menstrual cycles, decreased bone density, and sleep issues. Read this article for a more a comprehensive list.

The future of KD

KD holds exciting potential as supplemental treatment to a range of disorders affecting the global population. The possibility that we can reduce symptoms of diseases such as ALS and Alzheimer’s through diet is quite incredible.

But don’t be too quick to place KD on a pedestal and fall prey to its seductive promises. We have yet to perform large-scale placebo-controlled clinical trials, and are mostly in the early stages of research on its positive and negative implications for health.

If you are planning on trying KD, consult with your doctor first. As with any diet or medication, KD is not right for everyone.

Sources and further reading

👋 I am Danielle Gruber and I am a 17-year-old innovator at The Knowledge Society, with particular interests in neuroscience, computer science, math, and everything in-between.

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Danielle Gruber

👋 I am a freshman at Yale University majoring in electrical engineering. I’m interested in neuroscience, computer science, math, and everything in between!