Venous blood samples (2 ml) were obtained during all visits using a 22 G catheter inserted percutaneously into an antecubital vein. The catheter was kept patent using a saline flush following each sample collection. Additionally, during Study 1, arterialized blood from a catheter inserted into a heated hand (Forster et al., 1972) was collected into heparinized blood gas syringes (PICO 100, Radiometer, Copenhagen) from a subset of participants (n = 7) and immediately analyzed for pH and electrolytes using a clinical blood gas analyser (ABL, Radiometer, Copenhagen).
Also, it’s important to remember that just because something may be SAFE (and to reiterate, I’m not saying a long term ketogenic diet is safe), it doesn’t mean it’s good for you or beneficial. Running Marathons could be considered safe (especially if it’s on a closed race circuit), but does this mean it’s good for you? Or should you be out running marathons every day?
We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured.
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!).
Blood d-βHB, pH, bicarbonate (HCO3-) and electrolytes measured in arterialized blood samples from resting subjects (n = 7) following a ketone ester or salt drink containing 3.2 mmol.kg−1 of βHB. Shaded areas represent the normal range. Values are means ± SEM. (A) Venous blood d-βHB. (B) Arterialized blood pH. (C) Blood bicarbonate. (D) Blood potassium. (E) Blood sodium. (F) Blood chloride. †p < 0.05 difference between KE and KS, *p < 0.05 difference from baseline value.
Patrick Arnold is an organic chemist who is notorious for being the creator of several performance-enhancing steroids. He is arguably one of the strongest influencers on the advancement of sports supplementation. Currently he is focused on developing products under the KetoSports brand, which includes two exogenous ketone products – KetoForce and KetoCaNa.
After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle (which gave origin to the phrase ‘fat burns in the flame of carbohydrate') and for the supply of glucose to the central nervous system (CNS).4
When choosing an exogenous ketone supplement, make sure to read the ingredients carefully. Brands that have a “proprietary blend” don’t allow you to see the quantities of each ingredient in their mix. You should know every detail about the supplements you choose, so you know exactly what is affecting your body, and you have control over the variables of your intake.
Full disclosure: after carrying out the background research, I was already, as you might imagine, feeling a little less neutral about these products. You may have noticed a hint of that in part 1 of the 2-part video series we made about the project (watch part 2 at the top of this page!). However, and although this was by no means a controlled scientific study under laboratory conditions, we designed the experiment in a very objective way. The aim was to give the supplements the best possible chance of showing the benefits they are claimed to have.
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!
Possible GI distress (flatulence) at exceptionally high doses – In the studies referenced in this article, exogenous ketones taken in large doses occasionally resulted in GI distress, especially flatulence. However, the cause of this is hypothesized to be due to the fact that ketones were mixed in a milky fluid that wasn’t very palatable. If you’re taking a nominal dose of exogenous ketones the likelihood of GI distress is rather low. Moreover, if some GI distress is prevalent, it should improve as you become accustomed to taking ketones.
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 »
They’ve got enough science behind them to suggest they do work very well indeed, but watch out for the online ads featuring the raspberry ketone fat burners. Their name is little more than a parlour trick because this is not related in any way to ketones, a ketogenic diet or nutritional ketosis. They are merely the natural substance that gives raspberries their sweet aroma and flavour. Just because they’re marketed at the must-have fat burner, doesn’t mean they work and are one of the most widely spread Internet scams. There aren’t any human studies to back up raspberries claims so exercise a handful of caution when choosing your ketone supplier. Make sure they’re reputable, can be held accountable and are Australian made to set yourself up to become leaner while increasing your stamina.
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Increased calcium levels in the bloodstream may contribute to the hardening of arteries (atherosclerosis), which in turn can lead to a heart attack. Calcium from supplements enters the bloodstream in one bolus, whereas we usually tend to get calcium from foods in small doses from the breakdown process. This might explain why calcium from food doesn’t create the same risk that is introduced by calcium supplements. At first glance, it seems to be the case that high calcium intake –at least from supplements–may not be ideal.
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I had heard horror stories about how bad ketone esters tasted (like “rocket fuel”!) so was prepared for the worst. I followed their instructions and drank the contents of the bottle in one gulp, then chased it with a sip of sparkling mineral water. While not the most pleasant aftertaste, the flavor wasn’t any worse than after a shot of well tequila. Within 15 minutes I was already well into therapeutic ketosis, and after 30 minutes my ketone meter displayed a “HI” error message (meaning my level was greater than 8.0 mmol/L)!
As repeated KE consumption would be required to maintain nutritional ketosis, we investigated the kinetics of drinks in series and of continuous intra-gastric infusion. During starvation, the accumulation of ketones (>4 mM) reportedly inhibited ketone clearance from the blood, however the underlying mechanism is unknown (Hall et al., 1984; Wastney et al., 1984; Balasse and Fery, 1989). In Study 3, βHB uptake and elimination were identical for the second and third KE drinks, suggesting that βHB may have reached a pseudo-steady state should further identical boluses have been given at similar intervals. Furthermore, when the KE was given at a constant rate via a NG tube, blood ketone concentrations remained ~3 mM. Therefore, repeated KE drinks effectively maintain ketosis at the intervals and doses studied here.
BHB easily crosses the blood-brain barrier resulting in easily accessible energy to the brain and muscle tissues, becoming a source of energy after entering the mitochondria, being converted to Acetyl-CoA, and then ATP through the Krebs cycle (the same process that glucose goes through to become ATP). This ultimately results in many direct benefits, including:
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