A ketogenic diet is characterized by keeping carbohydrate intake to a maximum of approximately 50 grams/day, or 5% of daily energy intake, while protein consumption is moderate or high (e.g. ~1.2 to 1.5 g/kg/d).
The remaining 80% of energy intake is mostly from fats, with relative fat intake depending on the degree of displacement of carbohydrates and proteins. [1]
This type of macronutrient distribution leads to an increase in the production of ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone, which leads to a state of physiological ketosis, which is where ketone body concentrations in the plasma are elevated as compared to a mixed diet. [2]
Testosterone, the primary male sex hormone is vital for reproductive development and function.
Low endogenous testosterone is associated with an increased risk of chronic disease, including type 2 diabetes [3] and cardiovascular disease. [4]
In many respects, cortisol is biochemically opposed to testosterone, as the administration of exogenous cortisol lowers testosterone. The relationship between testosterone and cortisol likely stems from their respective anabolic and catabolic properties.
What are the traditionally known benefits of a low-carb diet?
Low-carb diets have been controversial for decades. Some people assert that these diets raise cholesterol and cause heart disease due to their high fat content. However, in most scientific studies, low-carb diets prove their worth as healthy and beneficial.
Here are 10 proven health benefits of low-carb and ketogenic diets:
How a keto / low carb diet impacts testosterone
A recent systematic review and meta-analysis demonstrated that moderate protein, low carb diets had no consistent effect on resting total testosterone, however high protein, low carb diets caused a large decrease (37%) in resting total testosterone. [11]
The mechanism behind this is that protein intake over 35% may outstrip the urea cycle's capacity to convert nitrogen derived from amino acid catabolism into urea, leading to hyperammonaemia and its toxic effects [12].
Testosterone has been shown to suppress the urea cycle [13] whereas glucocorticoids upregulate the urea cycle. In addition, the most pronounced decrease in resting cortisol was on the longest high protein, low carb diet study.
Therefore, the decrease in testosterone and increase in cortisol on high protein diets, may serve to upregulate the urea cycle and increase nitrogen excretion, thereby limiting the adverse effects of excess protein consumption.
Research also indicates that post-exercise total testosterone was higher on long-term moderate protein, low carb, and lower on short-term high protein, low carb diets.
The finding above that high protein, low-carb diets caused a large decrease in resting total testosterone, whereas long-term low carb diets had no effect on resting total testosterone, suggests the observed subgroup effects in post-exercise total testosterone are explained by protein intake rather than diet duration.
High protein intakes may depress post-exercise total testosterone to maintain upregulation of the urea cycle and increased nitrogen excretion, as previously mentioned above.
The finding that long-term moderate protein, low carb diets increased post-exercise total testosterone, may be due by the increase in blood cholesterol on low carb diets providing greater substrate for testosterone production, which is utilized in times of increased anabolic signaling, such as during exercise. [14]
The higher post-exercise total testosterone on moderate protein, low carb diets may signal an increased anabolic response to exercise, which would be advantageous, particularly in individuals with strength, power, or hypertrophy goals.
The indication that low carb diets increase post-exercise testosterone should be taken with caution due to the small sample size in these studies. This finding should be confirmed by future research.
How a keto / low carb diet impacts cortisol
The increase in resting cortisol on short but not long-term low carb diets, is likely tied to glucocorticoids’ roles in glucose homeostasis. Cortisol, glucagon, and gluconeogenesis [i.e., generation of glucose from certain non-carbohydrate carbon substrates (e.g. amino acids)] all increase on short, but not long-term low carb diets [15].
As glucocorticoids increase gluconeogenesis, the initial rise in cortisol may be partly responsible for a transient increase in gluconeogenesis, on short low carb diets.
Additionally, cortisol may rise to spare glucose for brain function, as the brain cannot significantly use fatty acids for fuel.
Glucocorticoids inhibit glucose uptake and oxidation in adipose tissue and skeletal muscle, thereby conserving glucose for brain function.
In contrast, endogenous ketone production increases sharply over the first 3 weeks of a very low carb diet [16], and ketones can be used for fuel by the brain. Thus, when ketones replace glucose for the majority of brain fuel, cortisol's glucose sparing effects are not needed, and thus levels may return to baseline.
Evidence also demonstrates the increase in cortisol during exercise was greater on low carb diets.
Moreover, this effect appears to persist post-adaptation to a low carb diet, although somewhat lessened. Interestingly, the rise in post-exercise cortisol was reduced in studies using carbohydrate supplements during exercise on high carb diets [17].
Thus, it appears the rise in cortisol during exercise is increased during times of low carbohydrate availability.
There are three possible, complementary explanations for this. Firstly, as glycogen stores are partially depleted on a low carb diet, cortisol may increase more sharply on low carb diets to facilitate increased gluconeogenesis during exercise.
Secondly, fat oxidation is higher on low carb versus high carb diets during exercise [15], and thus cortisol may increase to facilitate increased fat oxidation via inducing lipolysis in adipose tissue.
Thirdly, exercise upregulates skeletal muscle glucose uptake [18], thus cortisol may increase to preserve glucose for brain function.
The higher increase in cortisol during exercise on low carb vs high carb diets appears to persist post-adaptation. Classically, cortisol is thought to have immunosuppressive effects, however in spite of elevated post-exercise cortisol, low carb diets do not appear overtly immunosuppressive, according to other immune-markers [19].
The potential immunosuppressive effects of higher post-exercise cortisol may be intensified in athletes undergoing high volume training, and some caution may be advisable, until further research is undertaken.
Summary
The majority of evidence in the literature indicates an increase in resting and post-exercise cortisol on short-term low carb diets (<3 weeks). In addition, research shows that resting cortisol levels return to baseline after ∼3 weeks on a low carb diet, whereas post-exercise cortisol remains elevated.
However, due to the low number of studies and unexplained discrepancy in long-term low carb diets, more research is needed to confirm the latter effects.
Moderate protein, low carb diets appear to have no effect on resting total testosterone, although the decrease in resting total testosterone on randomized moderate protein, low carb studies, emphasizes the need for further randomized controlled trials.
Finally, high protein, low carb diets caused a large decrease in resting total testosterone, which indicates that individuals consuming such diets may need to be cautious about adverse endocrine effects.
What I recommend is that if a low carb diet is something you can adhere to and control your calories and lose weight, then it is fine. It is possible that you may lose some lean body mass but it won’t be dramatic.
However, if your goal is to maintain or gain the maximum amount of muscle possible, then a low carb diet is not recommended. You can learn more
here.
References:
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2. Hall, K.D., et al., Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men. Am J Clin Nutr, 2016. 104(2): p. 324-33.
3. Yao, Q.M., et al., Testosterone level and risk of type 2 diabetes in men: a systematic review and meta-analysis. Endocr Connect, 2018. 7(1): p. 220-231.
4. Corona, G., et al., Endogenous Testosterone Levels and Cardiovascular Risk: Meta-Analysis of Observational Studies. J Sex Med, 2018. 15(9): p. 1260-1271.
5. Wood, R.J., et al., Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL, and HDL subfraction distribution and size in overweight men. J Nutr, 2006. 136(2): p. 384-9.
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10. Volek, J., et al., Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutr Metab (Lond), 2004. 1(1): p. 13.
11. Whittaker, J. and M. Harris, Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis. Nutr Health, 2022: p. 2601060221083079.
12. Bilsborough, S. and N. Mann, A review of issues of dietary protein intake in humans. Int J Sport Nutr Exerc Metab, 2006. 16(2): p. 129-52.
13. Lam, T., et al., Testosterone prevents protein loss via the hepatic urea cycle in human. Eur J Endocrinol, 2017. 176(4): p. 489-496.
14. Pasiakos, S.M., Exercise and amino acid anabolic cell signaling and the regulation of skeletal muscle mass. Nutrients, 2012. 4(7): p. 740-58.
15. Webster, C.C., et al., Gluconeogenesis during endurance exercise in cyclists habituated to a long-term low carbohydrate high-fat diet. J Physiol, 2016. 594(15): p. 4389-405.
16. Vidic, V., et al., Effects of calorie restricted low carbohydrate high fat ketogenic vs. non-ketogenic diet on strength, body-composition, hormonal and lipid profile in trained middle-aged men. Clin Nutr, 2021. 40(4): p. 1495-1502.
17. Moreira, A., et al., Nutritional modulation of exercise-induced immunodepression in athletes: a systematic review and meta-analysis. Eur J Clin Nutr, 2007. 61(4): p. 443-60.
18. Evans, P.L., et al., Regulation of Skeletal Muscle Glucose Transport and Glucose Metabolism by Exercise Training. Nutrients, 2019. 11(10).
19. Shaw, D.M., et al., Adaptation to a ketogenic diet modulates adaptive and mucosal immune markers in trained male endurance athletes. Scand J Med Sci Sports, 2021. 31(1): p. 140-152.
