By: Robert A. Schinetsky

 Ketogenic diets are more popular than ever. One need only check Google Trends or see the “Keto Corner” in Vitamin Shoppe for proof that the public’s thirst for all things keto continues to swell. Due to this increasing interest, keto supplements, particularly exogenous ketones, have become the “bell of the ball” in the industry.

 Previously, we’ve discussed the topic of ketone supplements and exercise performance in our article “Ketone Sports Supplement Hype: Fact and Fiction. Do They Improve Exercise Performance?” And, in that article, we’ve shown that currently, the body of research does NOT support the idea that using exogenous ketones (BHB salts) improves exercise performance. In fact, it may even reduce performance!

 Today, we’re going to see if using BHB salts improves the most common reason people adopt a ketogenic diet -- weight loss.

 More specifically, do ketone supplements enhance weight loss, or do they stop fat loss?

 Let’s find out!

A Quick Primer on Ketosis and Exogenous Ketones

 We’ve discussed in great detailed all things keto, including the different types of ketones your body produces in our article on ketone supplements and sports performance, so see that if you want the full explanation. But, as a quick “refresher” of sorts, here’s a crash-course:

- If you’re following a relatively “standard” diet (whole grains, lean proteins, healthy fats, fruits, and veggies), your cells use glucose as their primary fuel.

- If you drastically change your diet and remove carbohydrate from it, your body no longer can run on glucose and must find another fuel to power itself.

- In the absence of carbohydrate, the body decides to use fat for fuel and enters ketosis -- a metabolic state characterized by elevated levels of blood ketones, created from the breakdown of fat.

- You don’t have to completely eliminate carbohydrates to enter ketosis. Fasting for prolonged periods of time or even strenuous exercise can transition you into ketosis.

- The body produces three ketone bodies when in ketosis -- beta-hydroxybutyrate (BHB), acetoacetate, and acetone, with BHB and acetoacetate being more prevalent.[1]

- BHB has been shown to inhibit histone deacetylase (HDAC), igniting a flurry of metabolic activity that leads to improvements in resiliency, metabolic health, and longevity.[2]

- BHB has also been shown to exert anti-aging effects via upregulation of hnRNP A1-induced Oct4-mediated Lamin B1 pathway in vascular cells.[3]

- To facilitate the transition to a ketogenic diet, many often supplement with exogenous ketones, in the form of BHB salts (acetoacetate is not stable in solution), to provide a source of readily accessible fuel, while the body “figures out” how to go from burning glucose to burning fat.[6]

- There is an insufficient amount of research regarding exogenous ketone salts and esters published demonstrating that supplementation eases the transition to ketosis or reduces symptoms of “keto flu” (i.e. brain fog, lethargy, muscle cramps, headaches, constipation)[7]

- Exogenous ketones typically involve the bonding of BHB to sodium, potassium, calcium or magnesium.

- Ketone esters are another form of exogenous ketone, but are less frequently used due to a combination of extremely poor palatability and high cost.

- One study has shown that consumption of exogenous ketones has increased blood levels of ketones by 300%[5], which many people have misinterpreted to mean that supplementing with BHB salts automatically puts them into nutritional ketosis.

- While BHB salts do increase serum BHB levels, researchers have stated that they are NOT ketogenic, and may actually inhibit the production of ketones bodies in the liver.[8]

 Now that you’ve got the basics down, let’s discuss further if consuming ketone supplements will enhance weight loss

Ketone Supplements & Weight Loss

Exogenous Ketones May Reduce Appetite

 One of the main reasons that keto enthusiasts believe that ketone supplements accelerate weight loss is based on the results of a small study involving 15 people that noted that individuals who consumed ketone esters reported feeling 50% less hungry after an overnight fast than those who drank a sugary beverage.[9] Researchers attributed this reduction in hunger to decreased levels of ghrelin. In case you weren’t aware, ghrelin is the hormone in the body that signals hunger, stimulates appetite, and increases food intake.

 What’s conveniently left out of the study’s annotations is that the lead researcher on the study, Dr. Brianna Stubbs, is also the research lead for HVMN[10], a biohacking company that sells a ketone ester product. Yet, this fact (and conflict of interest) was not mentioned in the study at all.

 Moving past this study, many people seeking to lose weight adopt a ketogenic diet due to the fact that it helps reduce appetite, even in the presence of weight loss.[11]

 However, what’s less clear is that ketone supplements will confer similar benefit in regards to appetite suppression as being in true nutritional ketosis. In fact, research notes that the ability of ketone supplements to elevate serum ketone levels is significantly impacted by whether or not you’re in a postprandial (after-meal) state.

 In other words, ketone supplements have a greater effect on increasing blood ketone levels when you’re fasted compared to when you’ve had a meal in the preceding few hours.[12,13,14]

 And, since researchers attribute the appetite suppressing effects of the ketogenic diet to elevated ketone levels in the blood, supplementing with exogenous ketones may only be beneficial in a fasted state, such as first thing in the morning.[9]

 In the end, there’s not enough evidence yet to clearly show that supplementing with exogenous ketones reduces appetite. It may help reduce appetite in a fasted state, but whether this is due to the fact that BHB salts elevate serum ketone levels and help reduce ghrelin, or simply because ketone supplements supply your body with calories remains to be seen.

Ketone Supplements Inhibit Fat Breakdown

 The main purpose people adopt a ketogenic diet for weight loss is to burn body fat. Depriving your body of carbohydrates forces it to rely on stored fat to use for energy, which it does by producing ketones.

 So, if the whole purpose of a diet is to force your body to rely on stored body fat, what sense does it make ingesting exogenous ketones. By feeding your body ketones, you’re reducing the amount of body fat your body will consume in order to power itself.

 Here’s another way to look at it. Ketone supplements increase blood levels of ketones. When blood levels of ketones are elevated, your body will autoregulate and stop cultivating fatty acids from adipose tissue to create its own ketones. Once it finishes using those supplemental ketones for energy, then it will resume ketone generation from body fat stores.

 The same would be true for the glucose-burning individual. If they have just consumed some type of carbohydrate-containing food, blood sugar levels rise, and the body will use that sugar first, instead of relying on stored glycogen in muscle or the liver.

 Furthermore, your body has feedback mechanisms that slow down ketone production if ketone levels get too high. So, if you’re constantly guzzling BHB salts all day long, your body will reduce its own ketone generation to prevent your blood from getting too acidic.[15,16,17] And when you consider that ketone supplements (BHB salts) can increase insulin secretion, thereby shutting off lipolysis, we’re hard pressed to see how ketone supplements enhance fat loss.

 In other words, if maximizing fat burning is your primary concern, supplementing with exogenous ketones shouldn’t be at the top of your priority list. Maintaining a strict calorie deficit should be.

 Speaking of calories, something you may not know about exogenous ketones is that…

Ketone Supplements Contain Calories

 To lose weight, you must be in a caloric deficit. Consuming less energy than your body requires forces your body to draw from its own energy stores (i.e. body fat). In the process, your body expends calories creating ketones, and subsequently derives energy from the ketone bodies to power its cells. This means that ketones have calories.

 In fact, exogenous ketones contain roughly 4 calories per gram -- the same number of calories as protein and carbohydrates.

 If the purpose of fat loss is to get your body to burn its own body fat and produce its own energy, what sense does it make to supplement with something that both contains calories and reduces the body's fat burning processes?

 Simply put, it doesn’t.

 And, if you think using ketone supplements helps transform you into a 24/7 fat-burning machine, think again. The effects of ketone supplements only last a few hours, meaning you’ll have to continually ingest them if you’re not truly in a state of nutritional ketosis.[15,18]

Ketone Supplements May Cause Insulin Resistance

 One other common reason people adopt a ketogenic diet is to reduce insulin secretion and improve insulin sensitivity. While, ketogenic diets have been noted to reduce plasma insulin concentrations by 50%, a pair of animal studies indicate that long term high-fat, ketogenic diets may lead to insulin resistance.[19,20]

 This suggests that in the event you do transition at some point in life to a diet that includes carbohydrates (and let’s face it, somewhere down the line you will eat some kind of carb whether it be a slice of pizza, sandwich, potato, or cupcake), you might be hindering your body’s ability to properly dispose of glucose, when the whole point of adopting a ketogenic diet in the first place was to improve insulin sensitivity.

Takeaway

 Ketone supplements are all the rage these days and viewed by many as a means to inducing ketosis and accelerating fat loss. Yet, despite the potential appetite-lowering effects of ketone supplements, their ability to significantly enhance weight loss is unproven at best, and at worst, they actually slow down the fat loss process. 

 In true ketosis, the body will make 150+ grams of ketones per day (when fully fat adapted), making the need to use ketone supplements superfluous. And, when you consider that most ketone supplements average $3 per serving (and don’t taste all that great), there really is no reason for the dieting individual to use them.

Therefore, if you’re interested in the ketogenic diet for improving health or losing weight, you’re best served to do it the right way and avoid relying on ketone supplements to mimic the effects of ketosis. Or, if you’re rather not have to go to the extremes of avoiding an entire macronutrient group, you can simply employ a moderate calorie deficit, which science has shown to be equally as effective for losing weight.

References

1. McPherson, P. A. C., & McEneny, J. (2012). The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress. Journal of Physiology and Biochemistry, 68(1), 141–151. https://doi.org/10.1007/s13105-011-0112-4
2. Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2013;25(1):42-52.
3. Young-min Han, Tatiana Bedarida, Ye Ding, Brian K. Somba, Qiulun Lu, Qilong Wang, Ping Song, Ming-Hui Zou. β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4. Molecular Cell, 2018; DOI: 10.1016/j.molcel.2018.07.036
4. Evans, M. , Cogan, K. E. and Egan, B. (2017), Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol, 595: 2857-2871. doi:1113/JP273185
5. James, S., & Kjerulf Greer, B. (2018). Influence of Exogenous beta-Hydroxybutyrate on Walking Economy and Rating of Perceived Exertion. Journal of Dietary Supplements, 1–7. https://doi.org/10.1080/19390211.2018.1471562
6. Cox, P. J., Kirk, T., Ashmore, T., Willerton, K., Evans, R., Smith, A., Clarke, K. (2016). Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metabolism, 24(2), 256–268. https://doi.org/10.1016/j.cmet.2016.07.010
7. Harvey CJDC, Schofield GM, Williden M. The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review. PeerJ. 2018;6:e4488. Published 2018 Mar 16. doi:10.7717/peerj.4488
8. Balasse & Neef (1975) Balasse EO, Neef MA. Inhibition of ketogenesis by ketone bodies in fasting humans. Metabolism: Clinical and Experimental. 1975;24(9):999–1007. doi: 10.1016/0026-0495(75)90092-X.
9. Stubbs BJ, Cox PJ, Evans RD, Cyranka M, Clarke K, de Wet H. A Ketone Ester Drink Lowers Human Ghrelin and Appetite. Obesity (Silver Spring). 2017;26(2):269-273.
10. https://hvmn.com/team/brianna-stubbs
11. Gibson, A. A., Seimon, R. V, Lee, C. M. Y., Ayre, J., Franklin, J., Markovic, T. P., … Sainsbury, A. (2015). Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obesity Reviews : An Official Journal of the International Association for the Study of Obesity, 16(1), 64–76. https://doi.org/10.1111/obr.12230
12. Stubbs BJ, Willerton K, Hyama S, et al. Concomitant meal ingestion alters levels of circulating ketone bodies following ketone ester drink [Abstract]. Proc Physiol Soc 34, PC235. Cardiff, UK; 2015
13. Stubbs BJ, Cox PJ, Evans RD, et al. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017;8:848. Published 2017 Oct 30. doi:10.3389/fphys.2017.00848
14. Pinckaers PJ, Churchward-Venne TA, Bailey D, van Loon LJ. Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype?. Sports Med. 2016;47(3):383-391.
15. Leckey JJ, Ross ML, Quod M, Hawley JA, Burke LM. Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists. Front Physiol. 2017;8:806. Published 2017 Oct 23. doi:10.3389/fphys.2017.00806
16. Evans M, Cogan KE, Egan B. Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol. 2016;595(9):2857-2871.
17. Taggart, A. K. P., Kero, J., Gan, X., Cai, T.-Q., Cheng, K., Ippolito, M., Waters, M. G. (2005). (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. The Journal of Biological Chemistry, 280(29), 26649–26652. https://doi.org/10.1074/jbc.C500213200
18. MADISON LL, MEBANE D, UNGER RH, LOCHNER A. THE HYPOGLYCEMIC ACTION OF KETONES. II. EVIDENCE FOR A STIMULATORY FEEDBACK OF KETONES ON THE PANCREATIC BETA CELLS. J Clin Invest. 1964;43(3):408-15.
19. Grandl G, Straub L, Rudigier C, et al. Short-term feeding of a ketogenic diet induces more severe hepatic insulin resistance than an obesogenic high-fat diet. J Physiol. 2018;596(19):4597-4609.
20. Jornayvaz FR, Jurczak MJ, Lee HY, et al. A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain. Am J Physiol Endocrinol Metab. 2010;299(5):E808-15.
21. Fery, F., & Balasse, E. O. (1985). Ketone body production and disposal in diabetic ketosis. A comparison with fasting ketosis. Diabetes, 34(4), 326–332.