Do exogenous ketones have benefits for a generally healthy adult, particularly for weight loss or athletic performance, considering potential risks and interactions with medical conditions such as diabetes?

Exogenous Ketones: Limited Evidence for Weight Loss or Athletic Performance in Healthy Adults

For generally healthy adults seeking weight loss or athletic performance enhancement, exogenous ketone supplements lack convincing evidence of benefit and should not be routinely recommended. The available research shows these products can safely elevate blood ketone levels but fail to demonstrate meaningful improvements in the outcomes that matter most.

Weight Loss: No Demonstrated Benefit

Exogenous ketones do not promote weight loss in healthy adults. A 28-day safety study of ketone monoester supplementation (25 ml three times daily) found no effect on body weight or body composition despite consistently elevating blood β-hydroxybutyrate to 4.1 mM 1. This contrasts sharply with endogenous ketosis from ketogenic diets, which produces weight loss primarily through caloric restriction and metabolic changes 2.

Key Distinction: Exogenous vs. Endogenous Ketosis

• Endogenous ketosis (from ketogenic diets) creates a metabolic state with decreased insulin levels, reduced ghrelin and leptin, 57% reduction in insulin resistance, and increased energy expenditure by approximately 52 kcal/day per 10% decrease in carbohydrate intake 2
• Exogenous ketones elevate blood ketones without these broader metabolic adaptations, producing "a similar, but far from identical, metabolic state" 3
• The weight loss benefits attributed to ketogenic diets come from the dietary restriction itself, not simply from elevated ketone levels 2

Athletic Performance: Insufficient Evidence

The evidence base for athletic performance enhancement is inadequate. While exogenous ketones are "rapidly entering the commercial marketspace" with "significant potential" claims, the research focuses primarily on safety and metabolic responses rather than performance outcomes 4. No high-quality studies demonstrate improved athletic performance in healthy adults.

Safety Profile: Generally Well-Tolerated

Exogenous ketone supplements appear safe for short-term use in healthy adults based on available data:

• 28-day consumption showed no adverse effects on kidney function, blood gases, electrolytes, cholesterol, triglycerides, or glucose 1
• Mild nausea occurred in only 6 of 2,016 drinks consumed (0.3%) 1
• Both ketone monoester (KME) and ketone monoester/salt (KMES) formulations are well-tolerated, with KMES having slightly better acceptability due to less aftertaste 4

Metabolic Effects

• Single doses elevate blood β-hydroxybutyrate to 2-3 mM within 15-30 minutes, returning to baseline within 3-4 hours 5, 4
• Acutely lower blood glucose, free fatty acids, and triglycerides 5
• KME drinks decrease blood pH by 0.10; KS drinks increase urinary pH from 5.7 to 8.5 5
• Less than 1.5% of ingested ketones are excreted in urine 5

Critical Considerations for Diabetes

For adults with type 2 diabetes, exogenous ketones do not improve glycemic control. The highest quality recent evidence shows:

• Acute ketone monoester ingestion (0.3 g/kg) did not lower fasting blood glucose in 18 adults with type 2 diabetes 6
• 14 days of thrice-daily premeal supplementation (15 g) did not improve glycemic control as measured by serum fructosamine in 15 adults with type 2 diabetes 6
• While acute ingestion increased insulin and lowered free fatty acids, this did not translate to improved glucose control 6

Diabetes-Specific Warnings

Ketogenic diets (not exogenous ketones specifically) carry serious risks in diabetes:

• Metabolic ketoacidosis is a hazard, particularly when combined with SGLT2 inhibitors 7
• Heart failure and neurological problems from thiamine deficiency have been reported with ketogenic diets 7
• Ketonemia from ketoacidosis or starvation ketosis must be avoided in pregnancy with diabetes 7
• Postoperative ketoacidosis can occur even when SGLT2 inhibitors are withheld for >72 hours 7

Special Populations to Avoid

Do not recommend exogenous ketones or ketogenic approaches for:

• Adolescents: Restrictive diets can trigger disordered eating patterns and should be limited to those >120% ideal body weight with serious medical complications 8
• Pregnant women with diabetes: Ketonemia must be avoided; it has been associated with lower intelligence scores in offspring at ages 2-5 years 7
• Malnourished individuals or cancer patients: Restrictive diets may worsen malnutrition 2
• Patients on SGLT2 inhibitors: Significantly increased ketoacidosis risk 7

Bottom Line

The evidence does not support recommending exogenous ketone supplements to healthy adults for weight loss or athletic performance. While safe for short-term use, they lack demonstrated efficacy for the outcomes patients seek. For weight management, evidence-based approaches include caloric restriction through balanced diets, increased physical activity, and behavioral modifications 7. The metabolic benefits attributed to ketosis are achieved through dietary ketogenic approaches, not by simply consuming ketone supplements 2, 3.