The ketogenic diet (KD), characterized by its high-fat, low-carbohydrate composition, has gained considerable attention over the last decade for its potential health benefits. This dietary approach induces complex systemic and metabolic changes, sparking innovative hypotheses that attempt to link biochemical adaptations to clinical effects. The ultimate goal for many researchers is to encapsulate the benefits of the KD into a convenient pill. However, the question remains: can the KD be effectively packaged into a pill?
The Quest for a Keto Pill: A Historical Perspective
The idea of simplifying the KD into a pill is not new. The KD experienced an initial surge of interest in the early 1920s, but its popularity waned with the advent of drugs like phenytoin. Over the past decade, significant progress has been made in understanding the mechanisms underlying the anticonvulsant and potentially neuroprotective effects of the KD. Researchers have embarked on a journey to reduce the "difficult" KD regimen to a simple pill, echoing the early history of the KD in the United States.
Understanding the Ketogenic Diet and Ketosis
The keto diet is a high-fat diet that keeps your body in a state of ketosis. It can help your metabolism speed up, increase your muscle mass and improve your blood pressure - all while helping you lose fat.
Ketosis is when your body uses ketones, a fatty acid, for energy instead of glucose. Keeping your body in ketosis can be hard - doing so includes eating a restricted list of foods like meat, eggs, nuts and fish and avoiding foods like fruit, sugar, beans and high-carb veggies.
The Allure of Keto Pills and Supplements
Given the challenges of adhering to a strict KD, it's not surprising that manufacturers have created keto supplements claiming to help you boost energy, burn fat, and lose weight fast. These supplements are marketed to help ameliorate the so-called "keto flu," an unofficial term referring to flu-like symptoms that can develop when switching to a keto diet.
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Types of Keto Supplements
The three most common types of keto diet supplements are:
- Keto pills: Many keto pills contain BHB salts or BHB esters and are promoted as a natural weight loss supplement.
- Keto powders: Similar to keto pills, keto powders contain some form of BHB. Many keto powder supplements may also include electrolytes to help people stay hydrated and remain in ketosis.
- Keto gummies: One of the newer keto supplements on the market, keto gummies are deceiving because many don’t actually contain any ketones. Instead, they are often made with apple cider vinegar, which companies say boosts metabolism and, therefore, promotes weight loss. However, there’s not enough scientific evidence to support this claim. Some keto gummies may also contain MCT oil and are sweetened with a non-nutritive sweetening agent, such as stevia.
Examining the Claims: Do Keto Pills Work?
The critical question is whether keto pills and supplements deliver on their promises. Despite the marketing hype, there's insufficient research to support the claim that taking keto pills, powders, or gummies will help you achieve ketosis or significant weight loss.
One small 2021 study found that people with obesity who followed a low-calorie ketogenic diet and took 24 grams of a BHB salt supplement per day for six weeks experienced enhanced ketosis. However, having higher levels of ketones in the blood didn’t seem to boost these participants' weight loss when compared to other groups, such as those following only the keto diet without the supplement.
Other research, such as this 2020 study, suggests that taking exogenous ketones can help boost concentrations of ketones in the blood quickly. Whether they have an appreciable effect on weight loss, however, is still murky, and more robust studies with strong evidence are lacking.
One of the reasons why supplementation may not be all that effective is that the body seeks to maintain an even level of ketones to prevent a potentially toxic buildup of these chemicals in the bloodstream. When the body senses that ketone levels are high, the liver stops making its own and will try to flush out excess ketones in your urine, a process called ketonuria.
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Ultimately, the jury is still out on whether or not these supplements work. But one thing is for certain: Experts do not recommend keto pills - or any diet pill, for that matter.
Potential Benefits and Risks of Keto Gummies
Keto gummies typically contain medium-chain triglycerides (MCTs), a type of saturated fat that helps give your body energy, in addition to exogenous ketones. Some may also contain gelatin or natural sweeteners like Stevia.
Potential benefits include:
- Increase weight loss.
- Improve athletic performance.
- Decrease your appetite.
However, whether keto gummies or other keto supplements can actually keep you in ketosis has been inconclusive, according to research.
Potential risks include:
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- Nausea and vomiting.
- Gastrointestinal issues, like diarrhea.
- Low blood sugar.
It's important to slowly introduce keto gummies to see how you do because you don’t want to all sudden just kind of overdo it and have those side effects and not be very happy. The keto diet - and the addition of a keto supplement like gummies - can potentially lower your blood sugar, leading to hypoglycemic responses and can dehydrate you as well.
The Role of Ketone Bodies
Ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone, are produced during ketosis and are believed to play a role in the KD's effects. Some studies have explored the direct effects of ketone bodies on brain function. Keith demonstrated in the early 1930s that acetoacetate prevented seizures induced by thujone in rabbits. Likhodii and colleagues (2003) later showed the broad anticonvulsant properties of acetone in four different animal models.
However, packaging acetoacetate or acetone into a pill presents significant challenges. Acetoacetate is highly unstable, and acetone can cause mucosal irritation. Oral ingestion of β-hydroxybutyrate formulations to achieve comparable concentrations observed in clinical practice may not be readily achievable.
Furthermore, recent studies have suggested that blood levels of ketones do not always correlate well with anticonvulsant effects. Ketone levels are known to vary considerably during the circadian cycle, influenced by feeding schedules and metabolism of foodstuffs.
Keto Pills and Fraud
In addition to health concerns, there’s a risk of scams with some keto products, namely supplements being pushed heavily on social media. In July 2020, AARP reported that two women in their 80s had been scammed out of more than $200 each when they purchased keto diet pills.
Scammers are using fake Shark Tank celebrity testimonials and endorsements - complete with doctored photos and videos - to generate buzz and profits.
Be wary of marketing text, such as “quick fix,” “guaranteed results” and “scientific breakthrough.” They’re usually a red flag of false advertising.
Because dietary supplement products are not regulated by the FDA, it can be difficult to know whether you’re getting what you pay for. If you're intent on purchasing a keto supplement, do your homework and ask the company to provide its research or evidence that the supplement does what the company is saying it does. A reputable manufacturer should be able to provide information about how its product has been tested and what it contains.
Alternative Mechanisms of KD Action
Beyond ketone bodies, other mechanisms have been proposed to explain the KD's effects. One theory suggests that increased ATP synthesis due to the KD produces a positive bioenergetic balance, stabilizing the resting membrane potential. Studies have shown that the KD can increase the total quantity of bioenergetic substrates and elevate the energy charge in the brain.
Another potential mechanism involves mitochondrial uncoupling proteins (UCPs), which are activated by fatty acids and decrease reactive oxygen species (ROS) formation. Upregulation of UCP2 expression has been linked to reduced seizure-induced neuronal cell death and enhanced ATP levels.
However, directly replicating these effects with interventions like chemical uncouplers (e.g., 2,4-dinitrophenol) is not feasible due to significant side effects.
The Role of Glutathione and Antioxidant Activity
The KD has been shown to enhance antioxidant activity in the brain. In rats fed a KD, studies have found increased glutathione peroxidase activity and upregulation of GSH biosynthesis. These changes may prevent mitochondrial DNA from oxidant-induced damage.
However, taking glutathione supplements is not an effective substitute for the KD, as available formulations are largely digested before they can reach the bloodstream and brain.
Glucose Restriction and Sirtuins
Glucose restriction is believed to be a key mechanism of KD action. Calorie restriction has been shown to reduce seizure susceptibility in rodents, and 2-deoxyglucose, which inhibits glycolysis, has demonstrated anticonvulsant activity in animal models.
One highly studied mechanism implicated in the clinical benefits of calorie restriction involves sirtuins, a family of enzymes that regulate gene expression. Calorie restriction increases the expression of Sirt1, the mammalian ortholog of Sir2, in various tissues, including the brain.
Cautions and Recommendations
Before you hop on the keto gummy bandwagon, consider making the necessary tweaks to your keto diet so you’re getting enough calories or fiber. Doing so can be a healthier option instead of turning to keto gummies. If you’re following the keto diet, everything seems to be running fine and you want to see a boost to your weight loss, then you could certainly try keto gummies.
If you’re considering the keto diet, ask yourself why you’re doing it and if it’s really worth it. Very restrictive diets are hard to follow, and they’re not sustainable. With the keto diet specifically, when we look at it for weight loss, most of that weight you’re losing quickly at the beginning is water weight. You’re not losing fat. It’s very exciting to see that number drop, but it’s not going to be metabolically better for you.