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Keto-flu, ketogenesis, and Carb-Tolerance: Part 2

A Summary of Our Research: How did people ‘feel’ on a keto diet?

Very little research has been conducted on people’s subjective experiences of diet. The study of this is incredibly important because if we are to properly understand diet and prescribe, based on holistic effects, we need to know how people feel!

Subjective perceptions of people on a keto-diet

We analysed this in a qualitative study.  We identified our participants subjective mood and experiences related to the ketogenic diet from daily diary entries and focus group findings.


Read more & listen to the audio below

A summary of our keto research, part 2.


Despite some initial challenges with the diet, especially gastrointestinal effects (mostly related to high levels of MCTs!), the overall perception of the diet was positive.

There were appreciable benefits for wellbeing, mood, sleep, and sugar cravings reported, with negative experiences decreasing as participants adapted to the keto-diet.3

These findings suggested that the overall experience of a very-low-carb keto diet is positive, but varies markedly between individuals.

The preceding studies suggested that increased ketonaemia might positively affect symptoms of carbohydrate withdrawal during keto-induction, and mood, but it is unclear whether diets differing in carbohydrate content and resulting in differing levels of ketonaemia would elicit similar effects.

Ketosis and keto-flu in non-keto low-carb diets

The final study of this collective body of work was a randomised clinical trial comparing a ketogenic diet, a low-carb diet and moderate-low-carb diet consisting of 5%, 15%, and 25% of total energy (TE) from carbohydrate respectively, over 12 weeks.4 The first three weeks of this study was used to compare blood ketones, symptoms of carbohydrate withdrawal (keto-flu), and mood between the dietary intervention groups.

Average blood levels of ketones (BOHB) were increased by 0.27 ± 0.32, 0.41 ± 0.38, and 0.62 ± 0.49 mmol/Lfor the moderate, low, and very-low-carb groups respectively (p = 0.013).

Ketosis was achieved consistently for both the keto-, and low-carb groups and sporadically for people in the moderate-low carb group.

Ketone levels between moderate (MCD), low (LCD), and very low (VLCKD) carb diet groups.


Overall, symptoms of ‘keto-flu’ between the groups were trivial, and while symptoms were increased most in the keto-diet group the differences between all groups were small and non-significant. Only halitosis (p = 0.039) and muscle weakness (p = 0.005) differed significantly between the groups with the largest effects seen in the keto-diet group.

Mood improved significantly from baseline

Mood improved significantly overall, with no significant difference between groups.

Change in mood disturbance by diet group. Note: a downward trend indicates less mood disturbance and better mood.

In perhaps the most interesting finding, although participants were instructed to maintain their habitual energy (calorie) intake, some people did restrict their eating. When calorie restriction DID occur, it was strongly associated with keto-flu. So, this suggests that any restriction of carbohydrate, not just ‘keto’ diets, if calorie-restricted can result in what was previously thought to be the ‘keto-flu’. I.e. it might have more to do with energy restriction, rather than just being from drastic carb-restriction.

There were only small differences observed between symptoms of carbohydrate withdrawal and mood between the diets ranging from 5-25% TE from carbohydrate

Which diet performed best overall?

In completers of our 12-week study, there were significant reductions in triglycerides (‘fat in the blood’), weight, and body mass index and increases in HDL, LDL, and total cholesterol.

Changes in key measures from different low-to-moderate carb diets.

It was more difficult for those in the VLCKD group to achieve the carbohydrate allocation of 5% calories from carbs, whereas those in the moderate-, and low-carb groups achieved their allocations more easily. Despite this, the positive effect on markers of health trended towards greater improvement from greater carbohydrate restriction with the largest improvements in HDL and triglycerides (perhaps THE most important of the health markers that we measured).

Change in carbohydrate intake as a % of overall energy intake. Line indicates 50th percentile.

What was the effect of baseline metabolic health?

Outcomes from lower- or higher-carbohydrate diets might be predicted by baseline metabolic health (i.e. how metabolically ‘disordered’ someone is).

Because adverse effects like keto-flu and mood differed by only a small amount between the diets, we also compared the effect of baseline cardiometabolic measures (lipid and other blood panels) on results, compared to the diet allocation.  

Participants with ‘poorer’ baseline measures benefitted most from greater carbohydrate restriction, with 7 of 11 measures improved most by a keto-diet. If these results were purely due to chance, we would only expect 3 or 4 of the measures to be most improved by keto.

Only HDL reached significance and initially indicated that poorer baseline (lower) HDL was more likely to be improved by a moderate carb restriction. On closer examination, it was seen that HDL worsened in as many people (only two in each group) regardless of diet, and the keto group had the greatest improvements in HDL overall.

This was the first study to compare a keto-diet to a low-carb diet and a more moderate restriction.

Although the effects need to be confirmed in research with larger numbers, the findings suggest that those with poorer baseline measures of cardiometabolic health might benefit most from greater carbohydrate restriction.

The findings suggest that those with poorer baseline measures of cardiometabolic health might benefit most from greater carbohydrate restriction.

References

1.          Balasse EO, Neef MA. Inhibition of ketogenesis by ketone bodies in fasting humans. Metabolism. 1975;24(9):999-1007.

2.          Harvey CJdC, Schofield GM, Williden M, McQuillan JA. The effect of medium chain triglycerides on time to nutritional ketosis and symptoms of keto-induction in healthy adults: a randomised controlled clinical trial. J Nutr Metab. 2018;2018:9.

3.          Harvey C, Schofield G, Williden M. The lived experience of healthy adults following a ketogenic diet: A qualitative study. J Holist Perf. 2018;7782018(1):3638.

4.          Harvey CJdC, Schofield GM, Zinn C, Thornley SJ, Crofts C, Merien FLR. Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial. PeerJ. 2019;7:e6273.

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