Exogenous ketones are becoming more popular as advancements in scientific research continue to show how they work to improve both health and performance. At first, the only options for delivering exogenous ketones were unpalatable ketone esters; however, exogenous ketones can now be taken in the form of ketone mineral salts that are more palatable and easily blended in water. Making ketone mineral salts involves combining beta-hydroxybutyrate (BHB) with mineral salts such as sodium, calcium, magnesium, or potassium. Before considering whether ketone supplements are a good option, most people immediately look at the salt load, and rightfully so. It is important to take into account the nutritional and health impact of not only the BHB but the minerals that are used to make the product.

Hi Mark, sorry this is off topic but not sure where to send a question for a future Ask Mark. I’m about to go into my yearly physical and I am wondering if there is any specific bloodwork that you like to do for your annual check up. I’m 47 year’s old and the than the basic blood work like lipid panel, etc..I’m going to ask my doctor to test my testosterone, HbA1C, fasting insulin, and Vitamin D levels. I’m also going to ask my doctor to do a stool test to check for parasites or other infections I may have picked up from open water swimming for triathlons. Can you recommend any other blood work that might be useful? Thanks!

For the first part of my experiment, I would simply record my blood ketone and glucose levels over a period of two hours after taking the ketone esters. While I am already fairly keto-adapted and can attain nutritional ketosis fairly easily (> 0.5 mmol/L), it wasn’t until the end of my Five-day Fasting Mimicking Diet that I was even close to reaching therapeutic ketosis levels (>5.0 mmol/L).

In terms of epigenetic signaling, initial studies of the effects of BOHB on class-1 histone deacetylase activity against oxidative stress (Schimazu 2013), NLRP3 inflammasome suppression (Youm 2015), mouse longevity (Roberts 2017), and other epigenetic regulatory effects suggest that levels as low as 1 mM have potent effects. Furthermore, the association between very mild ketonemia and reduced coronary mortality with SGLT2 inhibitor use in patients with type 2 diabetes (Ferranini 2016) suggests that there might be clinical benefits with chronic BOHB levels as low as 0.3 mM (Gormsen 2017. Vetter 2017).
Ketone Esters: These are not normally found in the body, but exogenous ketone esters convert into BHB once it is in the body. They are also synthetically (lab) made compounds that link an alcohol to a ketone body, which can then be metabolized by the liver into a ketone. They are like ketone salts on steroids as they have 5-10 time more BHB per serving/maximum daily intake than ketone salts. To date, pure ketone esters have been very expensive to produce and have only been available to researchers, elite athletes (Tour de France cyclists), and the US Department of Defense (people have spent more than $20,000 to have an independent lab produce a single serving!).
For the first part of my experiment, I would simply record my blood ketone and glucose levels over a period of two hours after taking the ketone esters. While I am already fairly keto-adapted and can attain nutritional ketosis fairly easily (> 0.5 mmol/L), it wasn’t until the end of my Five-day Fasting Mimicking Diet that I was even close to reaching therapeutic ketosis levels (>5.0 mmol/L).
Emerging evidence supports the therapeutic potential of the ketogenic diet (KD) for a variety of disease states, leading investigators to research methods of harnessing the benefits of nutritional ketosis without the dietary restrictions. The KD has been used as an effective non-pharmacological therapy for pediatric intractable seizures since the 1920s [1–3]. In addition to epilepsy, the ketogenic diet has elicited significant therapeutic effects for weight loss and type-2 diabetes (T2D) [4]. Several studies have shown significant weight loss on a high fat, low carbohydrate diet without significant elevations of serum cholesterol [5–12]. Another study demonstrated the safety and benefits of long-term application of the KD in T2D patients. Patients exhibited significant weight loss, reduction of blood glucose, and improvement of lipid markers after eating a well-formulated KD for 56 weeks [13]. Recently, researchers have begun to investigate the use of the KD as a treatment for acne, polycystic ovary syndrome (PCOS), cancer, amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI) and Alzheimer’s disease (AD) with promising preliminary results [14–26].

The other potentially important distinction between nutritional ketosis and chemically-induced ketosis is the potential metabolic role played by liver AcAc production and redox status. Although the ratio of BOHB to AcAc in venous blood is typically 80% to 20%, classic studies by Cahill (1975) have observed important hepatic vein and peripheral arterio-venous gradients for this ratio in keto-adapted patients. What these observations imply is that the liver produces a higher proportion of AcAc than is found in the peripheral blood, and that this is due to uptake of AcAc in peripheral cells (principally muscle) with re-release as BOHB. In the process, the reduction of AcAc to BOHB produces NAD+, which is beneficial to mitochondrial redox state and mitochondrial function (Verdin 2015, Newman 2017).
Hi. Thanks for the informative article! I have fallen down the exogenous ketone rabbit hole for the last 2 days trying to figure everything out. I am currently on a nutritional ketonic diet but after 8 months, I am finding it difficult to stay on it 100%. I would like to remain on a low-carb diet, but also have a little more flexibility in my food choices. If you take the expense out of the equation, which product would you recommend for someone who wants to use ketosis as a method of weight loss? Thank you so much.
I'm using this in conjunction with a low carb diet (40g net daily) and Adipex. Perfect Keto actually helped alleviate a lot of the keto/low carb flu symptoms I typically experience when starting a low carb diet. I can't give a full review on how this works with weight loss, because I'm just using it as a supplement (1 scoop) to help keep me in solid ketosis and have only been doing so for the past two weeks and using the low carb diet and Adipex in addition to this supplement doesn't give me a pure experience with this product. But I'm down 10 pounds in the two weeks, so I'm sure it's playing a part!
As ketone drinks can deliver nutritional ketosis without fasting, we investigated the effect of food on KE uptake and metabolism. It is well documented that food in the gut can slow, or prevent, the uptake of small hydrophilic hydrocarbons, such as βHB (Melander, 1978; Toothaker and Welling, 1980; Horowitz et al., 1989; Fraser et al., 1995), so decreased gut βHB uptake is probably the cause of lower blood βHB following the meal. Despite higher blood βHB concentrations in the fasted state, the meal did not alter plasma AcAc. This suggests that the rate of conversion of βHB to AcAc may not match the rate of appearance of βHB following KE consumption. Alternatively, meal-induced changes in the hepatic ratio of NAD+:NADH may have altered the conversion of βHB to AcAc (Himwich et al., 1937; Desrochers et al., 1992).
Skipping breakfast on a keto diet is a popular way to boost ketone levels. Despite the age-old myth that breakfast is the most important meal of the day, research shows that breakfast skipping is not only safe but beneficial. Skipping breakfast causes intermittent ketosis and also suppresses appetite [6]. Make sure your next meal of the day isn't too late in the evening as studies show that eating meals late at night causes weight gain and impairs fat metabolism [7].
Even Ben Greenfield Has Thyroid Problems While In Ketosis - “Ben describes one of the main side effects that he encountered being severe hypothyroidism… manifesting as severe sensitivity to cold, poor libido, and poor overall energy. The way they treated this was to eat a lot of liver, desiccated thyroid, and sweetbreads which seemed to fix things for him.”
If given all as a single salt, 50 grams per day of BOHB would mandate daily intakes of 5.8 g Mg++, 9.6 g Ca++, 11.0 g Na+, or 18.8 g K+. Even if divided up carefully as a mixture of these various salts, it would be problematic getting past 30 grams per day of BOHB intake. And again, most of the currently marketed ketone salt formulations are made with a mix of the D- and L-isomers of BOHB, so the actual delivered dose of the more desirable D-isomer is considerably less. The other concern with the salt formulations is that, as the salts of weak acids, they have an alkalinizing metabolic effect that might have a modest but cumulative effect on blood pH and renal function.
In a nutshell… WOW! The chart above shows each of the games/categories I played, showing my prior 5-day averages compared to the day I took the ketone esters. Compared to my baselines, my scores increased across the board, with the biggest improvements in spatial orientation (+32.2%), working memory (+23.7%), quantitative reasoning (21.5%), task switching (+14.9%), and information processing (+14.9%). Below are more detailed comparisons:
Hi Acadia, just want to clear up a few things you noted in your post: The manufacture of BHB salts involves ionic bonding of an anion (beta-hydroxybutyrate) with a cation (Na+, K+, Ca+, Mg+). At least one of the exogenous ketone products you listed does in fact contain potassium ions. People taking potassium-sparing drugs need to know this and that raises concerns about leaving it off your chart. Some people are genuinely sodium sensitive even to small amounts of salt added to otherwise healthy foods. This can hold true even for those following ketogenic diets. The term you’re looking for… Read more »

I also concluded that post by discussing the possibility of testing this (theoretical) idea in a real person, with the help of exogenous (i.e., synthetic) ketones. I have seen this effect in (unpublished) data in world class athletes not on a ketogenic diet who have supplemented with exogenous ketones (more on that, below). Case after case showed a small, but significant increase in sub-threshold performance (as an example, efforts longer than about 4 minutes all-out).

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