There have been studies done on long term ketogenic diets. This 2004 paper inn Experimental & Clinical Cardiology titled ‘Long-term effects of a ketogenic diet in obese patients’ concluded that obese patients following a ketogenic diet for 24 ‘reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.’
There have been studies done on long term ketogenic diets. This 2004 paper inn Experimental & Clinical Cardiology titled ‘Long-term effects of a ketogenic diet in obese patients’ concluded that obese patients following a ketogenic diet for 24 ‘reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.’
Although decreases in FFA, TG and glucose occurred, there were no significant differences between the KE and KS drinks or with intake amount. Ingestion of ketone drinks significantly decreased overall mean plasma FFA from 0.7 to 0.4 mM, TG from 1.1 to 0.9 mM and glucose from 5.7 to 4.8 mM after 1 h (all p < 0.05). Concentrations were the same as at baseline by 4 h, with FFA at 0.6 mM, TG at 0.9 mM and glucose 5.1 mM (Figures 2A–C). There was a rise in insulin concentrations 30 min following all drinks, probably due to the small amount of carbohydrate in the sweetener (Figure ​(Figure2D2D).
Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-βHB AUC of 1.3–1.4 moles.min.

The ‘carb-sparing’ effect from BHB suppresses the break down of muscle glycogen. This leads to lower lactate levels. When increasing exercise intensity, fat oxidation (burning) reaches a limit. At that point the muscle burns carbohydrates as fuel. But when consuming Ketone esters, the body does not make this switch. This suggests Ketones are being used instead. 11
BHB isn’t just an energy source for the brain–it has other effects which promote brain health. BHB can trigger the release of chemicals called neurotrophins, which support neuron function and synapse formation. One of these neurotrophins is called BDNF (brain-derived neurotrophic factor), which is a protein in the brain associated with cognitive enhancement, alleviation of depression and reduction of anxiety.10

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