CASE REPORT

published: 14 April 2022

doi: 10.3389/fendo.2022.830325

Case Report: Hypercholesterolemia

“Lean Mass Hyper-Responder”
Phenotype Presents in the Context
of a Low Saturated Fat
Carbohydrate-Restricted Diet
Nicholas G. Norwitz 1*, Adrian Soto-Mota 2, David Feldman 3, Stefanos Parpos 4,5
and Matthew Budoff 6
Edited by: 1 Harvard Medical School, Boston, MA, United States, 2 Metabolic Diseases Research Unit, National Institute for Medical
Liqing Yu,
Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico, 3 Citizen Science Foundation, Las Vegas, NV, United States,
University of Maryland, United States 4 Elfers Cardiovascular Center, Mass-General Brigham Newton-Wellesley Hospital, Newton, MA, United States,

Reviewed by: 5 Department of Medicine, Tufts University School of Medicine, Boston, MA, United States, 6 Lundquist Institute at Harbor-

Fengmei Lian, UCLA Medical Center, Torrance, CA, United States

China Academy of Chinese Medical
Sciences, China
Massimiliano Ruscica, Emerging evidence suggests that “leanness” and good metabolic health markers may
University of Milan, Italy predict larger increases in LDL cholesterol (LDL-C) in response to carbohydrate
*Correspondence: restriction. Specifically, a recent cohort study demonstrated an inverse association
Nicholas G. Norwitz
[email protected] between BMI and LDL-C change among individuals on carbohydrate-restricted diets
and identified a subgroup of “Lean Mass Hyper-Responders” (LMHR) who exhibit
Specialty section: exceptional increases in LDL-C, in the context of low triglycerides and high HDL-C. We
This article was submitted to
Obesity,
present the case of one subject, LM, who adopted a ketogenic diet for management of
a section of the journal ulcerative colitis. He subsequently experienced an increase in LDL-C from 95 to 545 mg/
Frontiers in Endocrinology
dl, at peak, in association with HDL-C >100 mg/dl and triglycerides ~40 mg/dl, typical of
Received: 07 December 2021
the emergent LMHR phenotype. Assessments of LM’s dietary intake, lipid panels, and
Accepted: 09 March 2022
Published: 14 April 2022 BMI are consistent with prior data and suggest that the LMHR phenomenon is not
Citation: dependent on saturated fat intake but inversely associates with BMI changes. Finally,
Norwitz NG, Soto-Mota A, computed tomography angiography conducted on LM after over 2 years of
Feldman D, Parpos S and
Budoff M (2022) Case Report:
hypercholesterolemia revealed no evidence of calcified or non-calcified plaque.
Hypercholesterolemia “Lean
Keywords: carbohydrate restriction, coronary computed tomography angiography (CCTA), ketogenic diet, lean
Mass Hyper-Responder”
mass hyper-responder, LDL cholesterol, HDL cholesterol, triglycerides
Phenotype Presents in the
Context of a Low Saturated Fat
Carbohydrate-Restricted Diet. Abbreviations: CCTA, Coronary Computed Tomography Angiography; CRD, Carbohydrate-restricted diet; HDL-C, HDL
Front. Endocrinol. 13:830325. cholesterol; LDL-C, LDL cholesterol; LMHR, Lean Mass Hyper-Responder; NEFA, Non-esterified fatty acids; TG,
doi: 10.3389/fendo.2022.830325 Triglycerides; TGRL, TG-rich lipoproteins; VLDL, Very-low-density lipoprotein.

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Norwitz et al. Lean Mass Hyper-Responder: Case Report

GRAPHICAL ABSTRACT | A recent cohort study of 548 persons on carbohydrate-restricted diets (CRDs) revealed inverse associations between triglyceride/HDL-C
ratio (TG/HDL-C) and LDL-C change, and between BMI and LDL-C change, on CRD. This means leaner persons with lower TG/HDL-C ratios generally exhibit larger
increases in LDL-C on CRD. Individuals with a particularly pronounced high LDL-C, high HDL-C, low TG ratio are termed "Lean Mass Hyper-Responders." This report
provides a clinical vignette of a patient who exhibits the Lean Mass Hyper-Responder phenotype, with LDL-C as high as 545 mg/dl, despite normal pre-CRD LDL-C of
95 mg/dl and consuming a CRD with a high unsaturated/saturated fat ratio. Coronary CT angiography conducted after 2.5 years of extremely elevated LDL-C reveals no
detectable plaque development.

INTRODUCTION mood disorders, autoimmune and inflammatory bowel disease,

as well as for general wellbeing or athletic performance. Indeed,
In 2017, co-author Dave Feldman observed a trend: individuals there has been the emergence of an LMHR Facebook group of
who were lean and athletic tended to observe larger increases in ~8,000 members and growing. However, whether the prevalence
LDL cholesterol (LDL-C) on carbohydrate-restricted diets of this population is increasing, or we are simply now
(CRDs). He also noted that these cases of diet-induced recognizing its existence, discussion of the phenotype has
increases in LDL-C co-occurred with increases in HDL-C and achieved medical community recognition as represented by
decreases in triglycerides (TG), giving rise to a combination lipid reference to LMHR in prior case series by others (2, 3).
profile opposite to that of atherogenic dyslipidemia. The cut However, until recently, the actual link between “leanness” and
points chosen to characterize this phenotype included LDL-C ≥ the aforementioned high LDL-C, high HDL-C, low TG lipid triad
200, HDL-C ≥ 80, and TG ≤ 70 mg/dl, and were selected on the had not been systematically assessed.
basis of empiric observation and based on the fact that each We recently performed a hypothesis-naïve exploratory
threshold is rare in the general population and, thus, the chance analysis on data drawn from a cohort of 548 people on CRD
that any individual would pass all three cut points and demonstrated that there is an inverse relationship between
simultaneously—rather than as part of a triad—is highly BMI and changes in LDL-C (as well as between TG/HDL-C
unlikely. This lipid triad was termed the “Lean Mass Hyper- ratio and changes in LDL-C), in the context of carbohydrate
Responder” (LMHR) phenotype (1), given the apparent lean restriction. Otherwise stated, leaner individuals with lower TG/
nature of individuals in whom it presented. HDL-C ratios are at greater risk for increases in LDL-C on a
Since the proposal of the LMHR phenotype almost 5 years CRD (4). Notably, 18% (n = 100) of participants in this study
ago, an increasing number of people have been self-reporting to fulfilled all three cut points of the LMHR phenotype, and were
meet all three LMHR criteria. This trend may be, in part, driven significantly leaner than other participants (Mean BMI, 22.0 ±
by the increasing popularity of CRD and ketogenic diets for the 2.7 kg/m2 for LMHR vs. 24.6 ± 4.1 kg/m2 for non-LMHR, p =
management of non-obesity-related conditions, such as epilepsy, 1.2 × 10−10). These data were the first to formally characterize

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Norwitz et al. Lean Mass Hyper-Responder: Case Report

cumulative over the week and BMI was measured the morning of each test using the same Withings Smart Body Cardio scale. Lipid data prior to ketogenic diet are included for comparison, though dietary data were not collected prior to
Calculations were performed using LM's dietary records (provided in Supplemental Information) and data extracted from USDA food central database in combination with brand-specific nutritional data, where applicable. Exercise volume is
LMHR as a unique metabolic sub-group, paving the way for

Dietary Fat Profile (%)

PUFA

13

14

20

9
–
future study of LMHR individuals.
We herein present the case of a 26-year-old LMHR male, LM,

MUFA
who adopted a ketogenic diet prioritizing unsaturated fat for the

70

71

62

46
–
management of ulcerative colitis and subsequently exhibited an
increase in LDL-C of over 400 mg/dl, along with increases in

Saturated
HDL-C and decreases in TG. LM’s case possesses distinctive and

17

15

18

45
–
useful features, including detailed information on dietary intake,
longitudinal lipid panels, and a recent Coronary Computed

Macronutrient
Tomography Angiography (CCTA) scan, that collectively

(% Calories)

Fat

83

84

83

82
–
provide a valuable clinical vignette in the context of the recent

Protein
classification of the LMHR phenotype. LM’s case also

14

14

14

16
–
demonstrates the challenges associated with the clinical
management of LMHRs and highlights the need for further

Net Carb
study of those with this phenotype.

2
–
Fiber

16

18

15

13
CASE DESCRIPTION

–
Macronutrients (g)

305

304

302

248
Fat
LM is a 26-year-old man with a medical history significant for

–
ulcerative colitis, diagnosed at age 21. Despite treatment with

Protein

112

113

116

115
TABLE 1 | Macronutrient intake and dietary fatty acid profile correspond to average daily intake over the 7 days prior to each blood test.
oral and suppository mesalamine and hydrocortisone enemas, he

–
was unable to remain in remission for longer than 8 weeks. At 23,
he experimentally adopted a Mediterranean-style ketogenic diet

Net Carb
[with an emphasis on intake of fatty seafood, extra virgin olive

24

18

25

12
–
oil, and low-carbohydrate fibrous fruits and vegetables (5)] and
entered a 6-month period of remission, following which he
Exercise (h)

elected to discontinue all medications and has largely remained

10.75

10.75

10.75

6.0
–
in remission. Since adopting a ketogenic diet two and a half years
ago, LM has only experienced colitis flares on three occasions:
twice when trying to reintroduce carbohydrates in the form of
Calories

3,272

3,225

3,265

2,783
honey, fruit, and/or starchy vegetables, and once following acute
–

mold exposure.
As previously reported (5), in the first 6 months following
BMI (kg/m2)

carbohydrate restriction, LM’s LDL-C increased from 95 mg/dl

19.3
18.8

18.7

19.6

20.2

to 321 mg/dl, along with low TG and an increase in HDL-C from

48 to 109 mg/dl. This change occurred despite LM’s self-reported
prioritization of foods rich in unsaturated fats, restricted intake
Weight (lb)

of saturated fat-rich foods, such as red meat and dairy, and

123
120

119

125

129

moderate fiber intake of ~30 g/day. Of note, LM subsequently

reduced intake of fiber in order to manage constipation, and
current intake is ~15 g/day.
(mg/dl)
TG

When statin therapy was recommended to LM upon first

76
47

58

40

39

LM measured food, raw mass, using a kitchen gram scale.

presentation with hypercholesterolemia, he declined. While he

(mg/dl)
HDL-C

expressed concern about his LDL-C levels, he also conveyed

113

116

116
48

94

reluctance about consenting to potentially lifelong

pharmacotherapy without first attempting to address his
(mg/dl)
LDL-C

hypercholesterolemia with diet and lifestyle change. LM

521

545

393

411
95

attempted on two occasions to reintroduce carbohydrates to

lower his LDL-C. On both occasions, he experienced near-
160
649

655

522

535
TC

immediate gastrointestinal discomfort and blood in the stool

May 2019 (Pre-keto)

within a week. Although he initially declined statins, he

consented to trial ezetimibe but experienced gastrointestinal
discomfort and discontinued treatment.
August 2020.

To further investigate potential contributing dietary factors to

his hypercholesterolemia within the context of his ketogenic diet,
Date

2020

2020

2021

2021
Sept
Aug

Jan

Oct

in August 2020, LM began measuring his dietary intake using a

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Norwitz et al. Lean Mass Hyper-Responder: Case Report

gram food scale and by keeping fastidious dietary records in the 7 was recommended to reduce dietary cholesterol intake, eliminating
days prior to scheduled lipid testing. Nutritional information liver, shellfish, and egg yolks from his diet (in substitution for lean
extracted from these records, using data exported from the chicken, fish, and egg whites). One month later, in September 2020,
USDA Food Central database along with brand-specific his LDL-C was re-measured at 545 mg/dl (HDL-C 94 mg/dl, TG 58
nutrition information, is provided with photographs of mg/dl). In January 2021, following a weight gain of 6 lbs and
representative meals in Supplemental Information. elevated intake of polyunsaturated fatty acid in the form of ~3 Tbsp
Lipid and metabolic panels over the years have been notable for toasted sesame oil daily, LDL-C was measured at 393 mg/dl (HDL-
elevated LDL-C-related markers, LDLp and apoB, and elevated C 116 mg/dl, TG 40 mg/dl). Finally, testing in October 2021
Lp(a) ranging from 109 to 168 mg/dl. Despite his low LDL-C while following further weight gain of 4 lbs (BMI 20.2 kg/m2), and in
consuming a mixed diet (95 mg/dl), Lp(a) was elevated in LM prior the context of a diet far richer in saturated fat, LDL-C measured at
to starting a ketogenic diet and is also elevated in LM’s father, who 411 mg/dl (HDL-C 116 mg/dl, TG 39 mg/dl) (Table 1
has a history of coronary artery disease manifesting in 99% left and Figure 1).
anterior descending stenosis at age 44, although the father presented After two and a half years of persistently elevated LDL-C
with a profile in strong contrast to his son: unremarkable LDL-C levels, and a prior CAC of 0, LM was again counseled to initiate
(70–92 mg/dl), atherogenic dyslipidemia (HDL-C 33–39 mg/dl, TG statin therapy. He considered, and a compromise was reached
199–294 mg/dl, with a preponderance of sdLDL), and history of whereby he agreed to initiate pharmacotherapy if “it was first
obesity. (NB: Subsequent to his event, the father adopted a CRD and proven” that he was developing measurable atherosclerotic
has lost 50 lbs and reversed metabolic syndrome, while maintaining plaque. Given consideration of data available at the time in
LDL-C <100 mg/dl on atorvastatin and ezetimibe). LM exhibits young people at elevated risk for ASCVD (6), and LM’s
normal thyroid and testosterone, HbA1c (4.8–5.0%), and fasting significant exposure (LDL-C ~400–550 for ~2.5 years), a CCTA
insulin (<3 mIU/ml), low hsCRP (<1.0 mg/L), Pattern A phenotype, was ordered for calcified and non-calcified plaques. No plaque or
and an extremely low TG/HDL-C ratio (~0.3) characteristic of the stenosis was observed in any vessels CAD-RADS = 0 (Figure 2).
LMHR phenotype. Whole exome sequencing performed by Veritas
Genetics, and independent dyslipidemia and ASCVD genetic risk
testing by GB Healthwatch, revealed no pathogenic or likely DISCUSSION
pathogenic variants that could account for LM’s phenotype.
Results of lipid panels conducted between August 2020 and In LM, LDL-C More Tightly
October 2021, in conjunction with data extracted from LM’s dietary Associated With Body Weight
records, are presented in Table 1 and Figure 1. In August 2020, Than With Saturated Fat Intake
LDL-C was 521 mg/dl (HDL-C 113 mg/dl, TG 47 mg/dl). This time LM’s BMI and LDL-C data reveal that an increase of 6–10 lb
point corresponds to LM’s BMI nadir of 18.8 kg/m2 and 83% body weight was associated with a >100 mg/dl drop in LDL-C.
unsaturated fat intake (17% saturated). In the following month, LM This presentation is consistent with prior cohort data (4), in

FIGURE 1 | Patient timeline. Above: LM experienced his first colitis flare in March 2017. Episodic flares persisted, despite treatment with oral and suppository
mesalamine and hydrocortisone enemas. LM commenced a ketogenic diet in June 2019, followed by a period of continued remission associated with ketosis.
Medications for colitis were discontinued. Below: Between August 2020 and October 2021, LM began a practice of fastidiously recording dietary intake (see
Supplemental Information) prior to scheduled lipid panels. Pie graphs represent fat pro!le of LM’s diet in the 7 days prior to testing. Further details provided in text,
Supplemental Information, and Table 1.

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Norwitz et al. Lean Mass Hyper-Responder: Case Report

Lean Mass Hyper-Responders on

Carbohydrate-Restricted Diets
Constitute a Unique Subgroup of
Individuals Not Represented in
NHANES Population-Level Data
While it may be self-evident that the LMHR triad of LDL-C ≥ 200,
HDL-C ≥ 80, and TG ≤ 70 mg/dl represents an atypical lipid
profile, it is worth emphasizing that patients bearing this
phenotype are extraordinarily rare among the general
population. For example, our analysis of the 70,310 patients in
the NHANES 1999–2020 database for which there are LDL-C,
HDL-C, and TG data reveals 513 patients with LDL-C ≥ 200,
4,641 with HDL-C ≥ 80, and 19,345 with TG ≤ 70 mg/dl.
However, only 3 cases passed the combined three criteria of the
LMHR phenotype (the publicly available code for this analysis can
be accessed at this link: https://github.com/AdrianSotoM/LMHR/
blob/main/LMHRSinNHANEScode.R). By contrast, our study of
548 people consuming CRD revealed that 18% (n = 100
individuals) were LMHR (4). The juxtaposition of the rarity of
LMHR throughout the general population (composed mostly of
people who are overweight, metabolically unhealthy, and/or eating
carbohydrate-rich diets) with the relative prevalence of LMHR in
leaner people consuming CRD is consistent with the notion that
the LMHR triad may reflect a unique underlying metabolic state.
FIGURE 2 | Computed tomographic angiogram demonstrating no coronary
artery disease. Left column: Volume-rendered reformations. Middle column: The Lipid Energy Model: An
Multiplanar reformation cross-sectional views. Right column: Curved
multiplanar reformations. LAD, Left anterior descending artery; LCx, Left Explanation for the Lean Mass
circumflex artery; RCA, Right coronary artery. Hyper-Responder Phenomenon
If low BMI, or perhaps more accurately low relative adiposity,
rather than elevated saturated fat intake drives the LMHR
which there was an inverse correlation between BMI and LDL-C phenotype, the question that inevitably follows is “why?” The
among 548 people on CRD. However, as LM’s records are Lipid Energy Model is a hypothesis that could explain the LMHR
longitudinal, they provide the logical extension of our prior phenomenon in patients like LM. While a formal description of
observation: they suggest that, for an LMHR on a CRD, the model is beyond the scope of this manuscript, we here offer a
becoming less lean could decrease LDL-C. The health brief primer.
implications of this potential strategy—weight gain—for In the context of carbohydrate restriction, there is a greater
lowering LDL-C in LMHR are unknown. demand by peripheral tissues for fat-based fuel. Aside from
More notably, LM’s data demonstrate that the LMHR ketone bodies, this can come from one of two sources: (i) non-
phenotype can exist in the context of a CRD that is relatively esterified fatty acids (NEFAs) released from adipocytes and (ii)
low in saturated fat. While this possibility was suggested by our TG-rich lipoproteins (TGRLs), including VLDL secreted by the
cohort data (given the low likelihood that lean metabolically liver. In the latter scenario, TGRLs undergo lipoprotein-lipase
healthy participants selectively consumed CRDs richer in (LPL)-mediated hydrolysis to supply TG from the lipoprotein
saturated fat, as compared with those with higher BMI and particles. The process of LPL-mediated remodeling of VLDL
TG/HDL-C ratio on CRDs), we were previously unable to yields surface remnants and core remnants, which contribute to
demonstrate that high relative intake of saturated fat is not increases in HDL-C and LDL-C, respectively (7).
required to produce the LMHR phenotype. However, LM’s In brief, the Lipid Energy Model postulates that, in leaner
dietary fat profiles were >80% unsaturated prior to the metabolically healthy individuals, there is an increase in VLDL
drawings of his two highest LDL-C (August and September secretion, LPL-mediated TG hydrolysis and VLDL turnover,
2020). Conversely, LM’s most recent labs, drawn following resulting in a profile of low TG, elevated HDL-C, and elevated
both weight gain and a marked increase saturated fat intake, LDL-C. Furthermore, the Lipid Energy Model predicts that the
reveal a relative decrease in LDL-C from peak. Thus, saturated fat rate of LPL-mediated VLDL turnover is related to energy
intake is not a primary driver of LDL-C change in LM. demands and inversely related to body fat mass, and thereby
Although LM’s data cannot be said to be generalizable to all provides a useful framework for hypothesis generation and
LMHR, they are consistent with prior data and suggest that BMI testing (Figure 3). Details and lines of evidence supporting this
is a more important determinant of LDL-C in LMHR than is Lipid Energy Model will be the subject of an upcoming review
saturated fat intake. (Norwitz et al. in preparation).

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Norwitz et al. Lean Mass Hyper-Responder: Case Report

FIGURE 3 | The Lipid Energy Model. (A) In the context of carbohydrate restriction, (1) glycogen depletion and (2) changes in circulating hormones stimulate
hormone-sensitive lipase (HSL)-mediated secretion of non-esterified fatty acids (NEFA) by adipocytes to fuel oxidative tissues. (3) The liver captures circulating NEFA
and repackages them into triglycerides (TG), (4) secreted aboard VLDL. (5) Increased lipoprotein-lipase (LPL)-mediated VLDL turnover generates increase of LDL-C
and HDL-C. (B) The magnitude of carbohydrate restriction, adiposity, and energy expenditure each contribute as independent variables to the degree of LPL-
mediated VLDL turnover and, thereby, to the magnitude of the high LDL-C, high HDL-C, low TG triad. Details and lines of evidence supporting this Lipid Energy
Model, along with suggestions for future experiments to assess the model, will be the subject of an upcoming review (Norwitz et al. in preparation).

Computed Tomography Angiography ordered (for the purposes of directing pharmacotherapy), it was
Shows No Evidence of Atherosclerotic reasonable to assume that he might exhibit plaque development
Plaque in LM based on the available data. This includes a study on young
LM’s CCTA data are difficult to interpret given his young age and adults with type II diabetes, mean HbA1c 7.9%, in which 80% of
the relative paucity of comparator data. At the time the scan was those above 25 years exhibited measurable plaque burden (6),

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Norwitz et al. Lean Mass Hyper-Responder: Case Report

and, of course, that children with homozygous familial PATIENT PERSPECTIVE

hypercholesterolemia and LDL-C levels comparable to LM can
present with xanthoma and suffer from myocardial infarctions in When I started my ketogenic diet, I regained a quality of life that
the first decade of life (8). For a direct example, patient 2 in I thought I had lost forever. Over the two prior years, my colitis
Luirink et al. (9) was diagnosed with homozygous familial symptoms were getting steadily worse, and I was losing the
hypercholesterolemia at age 0.9 years, with LDL-C of 548 mg/ ability to function, both academically and socially. Imagine a life
dl (similar to levels achieved by LM) and xanthomas (not present in which you had to continuously worry about having an
in LM). Following dual treatment with rosuvastatin and embarrassing and painful bathroom emergency at any time:
ezetimibe at 2.2 years and lipoprotein apheresis at 5.5 years, during an exam, or a car trip, on a date. How would you feel?
ultimately lowering LDL-C to 139 mg/dl, this patient’s first My ketogenic lifestyle did not just erase my physical symptoms,
CCTA at age 8 years revealed RCA and LAD plaques. His it gave me back a life.
years exposure to LDLC ~548 mg/dl (2.2 years) is similar to The rise in my LDL-C was an unforeseen consequence. At the
that of LM. Thus, without the benefit of hindsight, it was time, I had never heard of “Lean Mass Hyper-Responders”, and
reasonable to assume LM, age 26, could exhibit plaque on did not believe LDL-C could increase as high as mine did as a
CCTA. In retrospect, however, it can of course also reasonably result of diet. To my surprise, this phenomenon is somewhat
be argued that, despite the magnitude of his exposure, two and common and, as it turns out, there are thousands of people like
half years is insufficient for any measurable atherosclerotic me who are lean individuals who adopted a ketogenic diet and
plaque to precipitate. The absence of comparator data itself found that they felt better than they had in years, but at the “cost”
highlights the need for further study on the LMHR population. of exorbitantly high LDL-C.
As someone who considers himself scientifically inclined, I find
the LMHR phenotype both scary and fascinating. This appears to be
LIMITATIONS AND STRENGTHS a reproducible phenomenon in which lean people specifically are
able to manipulate their lipid levels to an astonishing degree by
LM’s case is subject to all the interpretive limitations of any case shifting the macronutrient composition of their diet. What is the
report. As singular patient data, his results cannot be assumed mechanism and what are the implications?
to be generalizable and are subject to the potential influences of I have also noticed that for many others who share my
individual genetics, diets, medication, disease stage, situation, this is neither something we have actively chosen nor
confounding lifestyle factors, and so on. These data should is it an issue most of us take lightly. Like myself, many have
also not be taken out of context and analogized to conditions of sought other means of reducing LDL-C but have conditions
high LDL-C/apoB in people consuming mixed diets. making it uniquely challenging for them. Speaking for myself, I
Furthermore, LM’s age obscures interpretation of his negative only want answers as to why my LDL-C increased and, more
CCTA and it is possible that he is at significantly increased risk importantly, greater insight into the risk associated with my
of ASCVD relative to other young adults. Nevertheless, LM’s LDL-C levels in myself as an individual patient. One can
case is notable for that patient’s fastidious records, which certainly and fairly argue the preponderance of evidence
suggest that the LMHR phenotype can exist in the context of supports lowering LDL-C, but I would also argue that LMHR
a CRD low in saturated fat, and for his negative CCTA data, are a unique subgroup that at least deserves further study so that
which are difficult to interpret but highlight the value of an patients like me can make more informed decisions, rather than
upcoming double-blinded prospective study that is already feeling like we are getting brushed under the rug.
underway to assess atherosclerotic plaque progression in a
sample of 100 LMHR.
DATA AVAILABILITY STATEMENT
CONCLUSION The original contributions presented in the study are included in
the article/Supplementary Material. Further inquiries can be
As suggested by our recent cohort data, the LMHR phenotype is directed to the corresponding author.
unique in that their high LDL-C appears (i) to be dependent on
dietary fuel preference, (ii) to be independent of known genetic
factors, (iii) to be inversely related to BMI, and (iv) to occur ETHICS STATEMENT
particularly in the context of low TG/HDL-C ratio. The
phenotype is also becoming increasingly common and more Ethical review and approval were not required for the study on
widely recognized in conjunction with the increasing popularity human participants in accordance with the local legislation and
of CRD and ketogenic diets. The case of LM is consistent with institutional requirements. The patients/participants provided
features of the phenotype as noted above (including independence their written informed consent to participate in this study.
from saturated fat intake in this individual) and further provides a Written informed consent was obtained from the individual(s)
clinical vignette emphasizing the mechanistic curiosities and for the publication of any potentially identifiable images or data
clinical complexities associated with LMHR phenotype. included in this article.

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Norwitz et al. Lean Mass Hyper-Responder: Case Report

AUTHOR CONTRIBUTIONS SUPPLEMENTARY MATERIAL

All authors listed have made a substantial, direct, and The Supplementary Material for this article can be found online
intellectual contribution to the work and approved it at: https://www.frontiersin.org/articles/10.3389/fendo.2022.
for publication. 830325/full#supplementary-material

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Identification of Noncalcified Plaque in Young Persons With Diabetes: An endorsed by the publisher.
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Frontiers in Endocrinology | www.frontiersin.org 8 April 2022 | Volume 13 | Article 830325