The ketogenic diet (KD) has gained significant popularity for its potential benefits in weight loss, improved insulin sensitivity, and even neurological conditions. This diet, characterized by very low carbohydrate intake, moderate protein intake, and high-fat intake, shifts the body's metabolism towards burning fat for fuel, producing ketone bodies. While the KD itself has potential side effects, the use of keto drops and other ketogenic supplements also warrants careful consideration due to their own set of potential adverse effects.
The Ketogenic Diet: A Metabolic Shift
A ketogenic diet (KD) typically involves a macronutrient mass ratio of 4:1 of fat to non-fat, with a carbohydrate intake of less than 50 g per day. This drastic reduction in carbohydrate intake forces the body to rely on fatty acids rather than glucose for energy, mimicking a starvation state. This process leads to increased ketogenesis, primarily in the liver, where ketone bodies such as β-hydroxybutyrate (βHB), acetoacetate (AcAc), and acetone are produced. These ketone bodies can then be used as an alternative fuel source by the body's cells, including the brain, which can derive up to 70% of its energy from ketone bodies during periods of reduced glucose availability.
Nutritional ketosis (NK) is a natural state that humans have relied on throughout evolution during times of low carbohydrate availability. It is important to distinguish NK from ketoacidosis, a pathological and dangerous state resulting from metabolic dysregulation seen in conditions like alcoholism and uncontrolled type 1 diabetes.
Keto Drops and Exogenous Ketones: An Overview
Keto drops, along with other keto supplements, often contain exogenous ketones, which are ketones derived from an external source. The intention behind taking these supplements is to elevate blood ketone levels, potentially mimicking the metabolic state of ketosis without adhering to a strict ketogenic diet. While the FDA does not regulate ketone supplements for their purity, safety, and effectiveness, they are readily available over the counter.
There are two main types of exogenous ketone supplements:
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- Ketone Salts: These are created by binding artificial ketones to electrolytes like sodium, calcium, magnesium, and potassium. While they can induce ketosis, they also carry the risk of electrolyte imbalances, particularly harmful for individuals with kidney disease.
- Ketone Esters: Considered the purest and most potent form of ketones, ketone esters work faster and maintain ketosis for a longer duration compared to ketone salts. They also pose a lower risk of electrolyte imbalances and may cause fewer gastrointestinal issues.
Medium-chain triglyceride (MCT) oil is another supplement often used in conjunction with ketogenic diets. While MCTs are rapidly absorbed and converted into ketones by the liver, they do not independently induce ketosis. They require the presence of a ketogenic diet or other exogenous ketone supplements to fully achieve a state of ketosis.
Potential Side Effects of Keto Drops and Ketogenic Supplements
While exogenous ketones may offer some benefits, it's crucial to be aware of the potential side effects associated with their use:
- Electrolyte Imbalance: Ketone salts, in particular, can lead to elevated electrolyte levels, which can be dangerous for individuals with medical conditions like kidney disease that affect electrolyte regulation.
- Gastrointestinal Distress: Some individuals may experience stomach upset, nausea, and diarrhea when taking ketone supplements. This can be due to the presence of sorbitol, a known laxative, in some keto gummies.
- Hypoglycemia: Ketogenic diets, and potentially the addition of keto supplements, can lower blood sugar levels, potentially leading to hypoglycemic responses. This is particularly concerning for individuals with diabetes who are taking medications to lower blood glucose levels.
- "Keto Flu": The transition into ketosis, whether through diet alone or with the aid of supplements, can trigger a cluster of symptoms known as the "keto flu." These symptoms may include headache, lightheadedness, fatigue, lethargy, "brain fog," decreased exercise capacity, mood changes, constipation, muscle cramps, diarrhea, and halitosis. These symptoms typically occur within the first few days of initiating a KD and usually resolve within 2-4 weeks.
- Halitosis: Bad breath, or halitosis, is a reported side effect of keto-induction.
- Constipation: A common side effect, especially in the pediatric population.
- Nausea and Vomiting: These are also common side effects, particularly in children.
- Decreased Energy: Feelings of fatigue, weakness, or lethargy are frequently reported during keto-induction.
- Light-headedness and Dizziness: These are relatively common transient symptoms in adults.
- Headache: Relatively frequent in adults.
- Reduced Exercise Performance: Impairment seems to last 3-4 weeks, with return to normal exercise capacity and performance upon “keto-adaptation” for most if not all adults
- Mood Changes: Studies reported in pediatric patients show an occurrence of irritability of 6.7 and 10% for the KD initiated with a gradual increase in calories or at goal calories, respectively.
- Muscle Cramps: A common symptom of keto-induction for the adult population
- Kidney Stones: A well-noted potential side effect of the ketogenic diet.
- Serious Muscle Loss: People on the ketogenic diet lose muscle even when they continue resistance training.
- Dehydration and a Loss of Electrolytes: The brain's favorite fuel is glucose, which is most easily created from carbohydrates. In very low carb diets, the brain has to adjust to using ketones from digested fats for energy. To add to this discomfort, your kidneys release more electrolytes as insulin levels fall.
- Nutrient Deficiencies: When carbohydrate intake is low, fiber consumption tends to be low, too.
- Bowel Problems: Many of the richest sources of fiber, like beans, fruit, and whole grains, are restricted on the ketogenic diet.
- Changes in Menstrual Cycle: Periods may become irregular or completely stop on the keto diet.
- High Cholesterol and an Increased Risk of Heart Disease: The ketogenic diet doesn’t put a cap on saturated fat, which has been associated with adverse health effects.
Potential Benefits of Keto Drops and Ketogenic Supplements
Despite the potential risks, some studies suggest potential benefits of exogenous ketones:
- Induction of Ketosis: Exogenous ketones can effectively induce ketosis, as demonstrated in studies where participants consuming ketone esters or ketone salts experienced elevated ketone levels.
- Potential Effects on Athletic Performance: Some research suggests that exogenous ketones may have an effect on the brain, heart, and skeletal muscle, which may have benefits to athletes.
- Potential for Psychiatric Disorders and Epilepsy treatment: Some experts theorize that the metabolism-altering effects of exogenous ketones may help treat these disorders.
However, it's important to note that the evidence supporting these benefits is still limited, and more research is needed to determine the long-term effects and safety of ketone supplements.
Cautions and Recommendations
Before considering keto drops or any ketogenic supplements, it is crucial to consult with a healthcare professional. This is especially important for individuals with pre-existing health conditions, such as diabetes, kidney disease, or heart disease, as well as those who are pregnant or breastfeeding.
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It's also important to remember that keto supplements are not a substitute for a healthy diet and lifestyle. Relying solely on supplements without making necessary dietary changes may not be effective and could potentially lead to adverse health outcomes.
Consider the following recommendations:
- Prioritize a well-formulated ketogenic diet: Focus on whole, unprocessed foods that are naturally low in carbohydrates and high in healthy fats.
- Address underlying reasons for difficulty staying in ketosis: If you're struggling to maintain ketosis, evaluate your carbohydrate intake, calorie intake, and overall dietary choices.
- Introduce keto supplements gradually: If you choose to try keto supplements, start with a small dose and monitor your body's response.
- Stay hydrated and replenish electrolytes: Drink plenty of water and consider supplementing with electrolytes like sodium, potassium, and magnesium to prevent dehydration and imbalances.
- Be mindful of potential interactions: If you're taking any medications, be aware of potential interactions with keto supplements. For example, raspberry ketone may reduce the effects of warfarin, a blood thinner.
The Importance of a Holistic Approach
The ketogenic diet and the use of keto supplements should be approached with caution and a comprehensive understanding of the potential benefits and risks. A holistic approach that prioritizes a well-formulated diet, regular exercise, and consultation with a healthcare professional is essential for achieving optimal health outcomes.
Hypoglycemia and the Ketogenic Diet
There has been a few case reports and case series of individuals developing hypoglycemia due to the ketogenic diet, with most of those reported in children
In one report of children treated for epilepsy with the ketogenic diet, about 28% were found to develop hypoglycemia (defined in this age population as serum glucose < 40 mg/dL), with younger age being a risk factor
Important work published by Cryer and colleagues in the past 50 years have described the counterregulatory responses to hypoglycemia, and defined the hypoglycemia-associated autonomic failure (HAAF) syndrome as hypoglycemia unawareness, when individuals do not perceive neurogenic warning symptoms of hypoglycemia.
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A recent study in mice showed that there was blunting of glucagon release to hypoglycemia in mice fed a ketogenic diet, suggesting a mechanism for increased risk of hypoglycemia on this diet. On the other hand, the ketogenic diet has been found to protect against hypoglycemia-induced neuronal damage in animals and humans.
In normal alcohol metabolism, the ingested ethanol is oxidized to acetaldehyde and then to acetic acid with the enzyme alcohol dehydrogenase, and nicotinamide adenine dinucleotide (NAD+) is reduced to NADH. An increased NADH/NAD+ ratio has been shown to suppress hepatic gluconeogenesis and reduce free glucose, perpetuating ketogenesis and hypoglycemia