Elevated LDL-cholesterol levels among lean mass hyper-responders on low-carbohydrate ketogenic diets deserve urgent clinical attention and further research

Norwitz, Nicholas G.; Mindrum, Michael R.; Giral, Philippe; Kontush, Anatol; Soto-Mota, Adrián; Wood, Thomas H.; D’Agostino, Dominic P.; Manubolu, Venkat Sanjay; Budoff, Matthew J.; Krauss, Ronald M.

doi:10.1016/j.jacl.2022.10.010

Cited by 9 publications

(13 citation statements)

References 9 publications

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“…The second point relates to the definition of the LMHR and KD. Dave Feldman initially described LMHR phenotype as presentation of low TG and high HDL‐C levels, with similar subsequent reports 2,3 . However, there are many ambiguities in this definition.…”

Section: Discussionmentioning

confidence: 99%

“…Although LMHR phenotype was proposed, there are widely varying modern dietary habits including KD 14 . In addition, there are various types of ketogenic diets which may result in diverse lipid profiles, and some cases may not meet the criteria for “typical LMHR phenotype.” LMHR phenotype is defined based on the consumption of the CRD or KD, and lipid profile 3 . Since there are various types of CRD or KD with varying amounts of proteins, carbohydrate, and fats, the definition of these diets is unclear 15–17 .…”

Section: Discussionmentioning

confidence: 99%

“…

The lean mass hyper responder (LMHR) phenotype is characterized by a pronounced increase in low-density lipoprotein cholesterol (LDL-C) levels upon reduction in dietary carbohydrate intake and substitution with fats and proteins for caloric compensation. [1][2][3] Patients with the LMHR phenotype typically have a lean physique, decreased triglyceride (TG) levels, and increased highdensity lipoprotein cholesterol (HDL-C) levels. [1][2][3] In other words, under the current definition, there are no cases of LMHR with elevated TG levels.

| CASE HISTORY/EXAMINATIONA 47-year-old man presented to our outpatient clinic with increased LDL-C levels (274 mg/dL).

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mentioning

confidence: 99%

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The impact of dietary fat type on lipid profiles in lean mass hyper‐responder phenotype

Takemura,

Inoue,

Matsunaga

et al. 2024

Clinical Case Reports

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Key Clinical MessageAlthough the lean mass hyper‐responder (LMHR) phenotype is well known, its diagnosis is impeded by the influence of fat type and intake on the lipid profile. Accordingly, a detailed assessment is warranted if LMHR is suspected.AbstractA 47‐year‐old man with suspected familial hypercholesterolemia presented with elevated triglyceride and low‐density lipoprotein cholesterol levels. He had adhered to a ketogenic diet and was suspected of a lean mass hyper‐responder phenotype; however, his lipid profile did not meet the definition. His lipid profile improved through dietary management without medication.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…

| CASE HISTORY/EXAMINATIONA 47-year-old man presented to our outpatient clinic with increased LDL-C levels (274 mg/dL).

…”

mentioning

confidence: 99%

See 1 more Smart Citation

The impact of dietary fat type on lipid profiles in lean mass hyper‐responder phenotype

Takemura,

Inoue,

Matsunaga

et al. 2024

Clinical Case Reports

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show abstract

“…A curious observation concerns lean individuals with low triglycerides and high HDL-cholesterol who may develop a marked increase in plasma LDL-cholesterol when consuming a very low-carbohydrate ketogenic diet, a phenomenon, which has been termed the lean mass hyper-responder (LMHR) phenotype [ 85 , 86 ]. This phenotype was defined as LDL-cholesterol ≥200 mg/dL, HDL-cholesterol ≥80 mg/dL, and triglycerides ≤70 mg/dL.…”

Section: Ketone Bodies and The Heart/a Double-edged Swordmentioning

confidence: 99%

Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue

Manolis

2023

IJMS

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The increased metabolic activity of the heart as a pump involves a high demand of mitochondrial adenosine triphosphate (ATP) production for its mechanical and electrical activities accomplished mainly via oxidative phosphorylation, supplying up to 95% of the necessary ATP production, with the rest attained by substrate-level phosphorylation in glycolysis. In the normal human heart, fatty acids provide the principal fuel (40–70%) for ATP generation, followed mainly by glucose (20–30%), and to a lesser degree (<5%) by other substrates (lactate, ketones, pyruvate and amino acids). Although ketones contribute 4–15% under normal situations, the rate of glucose use is drastically diminished in the hypertrophied and failing heart which switches to ketone bodies as an alternate fuel which are oxidized in lieu of glucose, and if adequately abundant, they reduce myocardial fat delivery and usage. Increasing cardiac ketone body oxidation appears beneficial in the context of heart failure (HF) and other pathological cardiovascular (CV) conditions. Also, an enhanced expression of genes crucial for ketone break down facilitates fat or ketone usage which averts or slows down HF, potentially by avoiding the use of glucose-derived carbon needed for anabolic processes. These issues of ketone body utilization in HF and other CV diseases are herein reviewed and pictorially illustrated.

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“…Increased saturated fatty acid intake has an unpredictable effect on lipids (a surrogate marker for CVD). [124][125][126][127][128] Reduced dietary fibre has potentially negative effects on gut metabolites and microbiota, which may increase the risk of CVD, gastrointestinal and other diseases. [129][130][131] Finally, the potential effect of LC/KD on medications is important.…”

Section: Westernmentioning

confidence: 99%

Efficacy of low carbohydrate and ketogenic diets in treating mood and anxiety disorders: systematic review and implications for clinical practice

et al. 2023

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Background There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. Aims To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders. Method MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367. Results The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis; diet duration: 2 weeks to 3 years; n = 389; age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some individuals. Conclusions Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.

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Elevated LDL-cholesterol levels among lean mass hyper-responders on low-carbohydrate ketogenic diets deserve urgent clinical attention and further research

Cited by 9 publications

References 9 publications

The impact of dietary fat type on lipid profiles in lean mass hyper‐responder phenotype

The impact of dietary fat type on lipid profiles in lean mass hyper‐responder phenotype

Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue

Efficacy of low carbohydrate and ketogenic diets in treating mood and anxiety disorders: systematic review and implications for clinical practice

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