A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity

doi:10.1016/j.amjmed.2004.04.009

The American Journal of Medicine

Volume 117, Issue 6, 15 September 2004, Pages 398-405

https://doi.org/10.1016/j.amjmed.2004.04.009 Get rights and content

Purpose

To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects.

Methods

We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months.

Results

Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference = −0.26 mg/dL, P = 0.03) but more frequently developed detectable chylomicrons (44% vs. 22%, P = 0.04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = −30 nmol/L, P = 0.74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, P = 0.63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (>3 mg/dL, n = 48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference = −2.0 mg/dL, P = 0.005), independent of weight loss.

Conclusion

In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions, and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions.

Section snippets

Methods

The enrollment criteria, randomization process, and study design of the primary study have been previously described (3). This study was approved by the Institutional Review Committee at the Philadelphia Veterans Affairs Medical Center, and all participating subjects gave informed consent. We enrolled 132 subjects from the outpatient practices of the Philadelphia Veterans Affairs Medical Center who had a body mass index ≥35 kg/m² and randomly assigned them to either a low-carbohydrate (n = 64)

Results

Many subjects had diabetes (40% [31/78]), and among those without diabetes, an additional 36 subjects had metabolic syndrome (Table 1). There were no significant differences in baseline characteristics between diet groups for the 78 subjects included in the study. When compared with those who had dropped out, the 78 subjects who remained in the study were slightly older and more likely to use lipid-lowering medications. Women who had been assigned to the low-carbohydrate diet were more likely

Discussion

In this randomized 6-month trial, we compared the effects of a low-carbohydrate diet with those of a conventional diet on lipoprotein subfractions and C-reactive protein levels in severely obese subjects. It is important that these factors be evaluated, especially given the concerns that improvements in conventional lipid parameters with a low-carbohydrate diet might obscure the deleterious effects on lipid subfractions and inflammation resulting from liberalized fat intake (22).

We found that

Acknowledgment

The authors gratefully acknowledge Dr. James Otvos and LipoScience Inc for technical contributions, Dr. David Freedman for his helpful comments on the analyses, and Megan L. Wolfe for assistance with the C-reactive protein assays.

References (32)

R.L. Karvetti et al.
Validity of the 24-hour dietary recall
Contin Educ
(1985)
S.M. Grundy et al.
Hepatic lipase influences high density lipoprotein subclass distribution in normotriglyceridemic mengenetic and pharmacological evidence
J Lipid Res
(1999)
M. Ai et al.
Relationship between plasma insulin concentration and plasma remnant lipoprotein response to an oral fat load in patients with type 2 diabetes
J Am Coll Cardiol
(2001)
N.E. Miller
Associations of high density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis
Am Heart J
(1987)
A. Festa et al.
LDL particle size in relation to insulin, proinsulin, and insulin sensitivityThe Insulin Resistance Atherosclerosis Study
Diabetes Care
(1999)
H.S. Kang et al.
Low-density lipoprotein particle size, central obesity, cardiovascular fitness, and insulin resistance syndrome markers in obese youths
Int J Obes Relat Metab Disord
(2002)
F.F. Samaha et al.
Low carbohydrate as compared to low fat diet in severe obesity
N Engl J Med
(2003)
G.D. Foster et al.
A multi-center, randomized, controlled trial of a low-carbohydrate diet for obesity
N Engl J Med
(2003)
Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection,...
J.D. Otvos et al.
Measurement issues related to lipoprotein heterogeneity
Am J Cardiol
(2002)

G.J. Blake et al.

Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women

Circulation

(2002)

P.T. Williams et al.

Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men

Circulation

(1990)

A. Festa et al.

Chronic subclinical inflammation as part of the insulin resistance syndromethe Insulin Resistance Atherosclerosis Study (IRAS)

Circulation

(2000)

ATP III Final Report. II. Rationale for intervention. Circulation....

M. Laimer et al.

Markers of chronic inflammation and obesitya prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention

Int J Obes Relat Metab Disord

(2002)

A. Tchernof et al.

Weight loss reduces C-reactive protein levels in obese postmenopausal women

Circulation

(2002)

Cited by (142)

Increased low-density lipoprotein cholesterol on a low-carbohydrate diet in adults with normal but not high body weight: A meta-analysis
2024, American Journal of Clinical Nutrition
Low-density lipoprotein (LDL) cholesterol change with consumption of a low-carbohydrate diet (LCD) is highly variable. Identifying the source of this heterogeneity could guide clinical decision-making.
To evaluate LDL cholesterol change in randomized controlled trials involving LCDs, with a focus on body mass index (BMI) in kg/m².
Three electronic indexes (Pubmed, EBSCO, and Scielo) were searched for studies between 1 January, 2003 and 20 December, 2022. Two independent reviewers identified randomized controlled trials involving adults consuming <130 g/d carbohydrate and reporting BMI and LDL cholesterol change or equivalent data. Two investigators extracted relevant data, which were validated by other investigators. Data were analyzed using a random-effects model and contrasted with results of pooled individual participant data.
Forty-one trials with 1379 participants and a mean intervention duration of 19.4 wk were included. In a meta-regression accounting for 51.4% of the observed variability on LCDs, mean baseline BMI had a strong inverse association with LDL cholesterol change [β = –2.5 mg/dL/BMI unit, 95% confidence interval (CI): –3.7, –1.4], whereas saturated fat amount was not significantly associated with LDL cholesterol change. For trials with mean baseline BMI <25, LDL cholesterol increased by 41 mg/dL (95% CI: 19.6, 63.3) on the LCD. By contrast, for trials with a mean of BMI 25–<35, LDL cholesterol did not change, and for trials with a mean BMI ≥35, LDL cholesterol decreased by 7 mg/dL (95% CI: –12.1, –1.3). Using individual participant data, the relationship between BMI and LDL cholesterol change was not observed on higher-carbohydrate diets.
A substantial increase in LDL cholesterol is likely for individuals with low but not high BMI with consumption of an LCD, findings that may help guide individualized nutritional management of cardiovascular disease risk. As carbohydrate restriction tends to improve other lipid and nonlipid risk factors, the clinical significance of isolated LDL cholesterol elevation in this context warrants investigation.
This trial was registered at PROSPERO as CRD42022299278.
Dietary pattern in women with polycystic ovary syndrome with and without associated non-alcoholic fatty liver disease: A cross-sectional study
2023, Clinics
Women with Polycystic Ovary Syndrome (PCOS) have a higher prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) than the general population. PCOS and NAFLD have common metabolic risk factors, however, the role of diet in NAFLD development is still uncertain in PCOS women.
To evaluate and compare the dietary patterns and nutritional intake in patients with PCOS with and without NAFLD.
Cross-sectional study that included patients with PCOS diagnosed according to Rotterdam criteria. All participants were submitted to abdominal ultrasound to investigate liver steatosis. Dietary profile was assessed by 24-hour food recall (24hR), and Food Frequency Questionnaire (FFQ). Diet quality was assessed by the Healthy Eating Index (HEI) adapted for the Brazilian population. Physical activity practice was also assessed.
87 participants were included (average age 35.2 ± 5.7 years), among whom, 67 (77%) had NAFLD. The group with PCOS and NAFLD presented higher body mass index (BMI) (34.9 ± 4.5 vs. 30.4 ± 4.9 kg/m2; p = 0.001), Waist Circumference (WC) (103 [97‒113] vs. 95 [87.5‒100] cm; p < 0.001) and were considered physically active less frequently than those without NAFLD (34.3% vs. 60%; p = 0.04). Food intake and dietary patterns assessed by 24hR, FFQ and HEI presented no difference between the groups.
PCOS women with coexistent NAFLD had higher BMI, WC and were less physically active than those without NAFLD. Dietary evaluation showed that PCOS women with NAFLD had no significant difference in macro and micronutrients or food group intake and diet quality in comparison to those without NAFLD.
Sugar-Sweetened Beverage Consumption and Plasma Lipoprotein Cholesterol, Apolipoprotein, and Lipoprotein Particle Size Concentrations in US Adults
2022, Journal of Nutrition
Prospective cohort studies have found a relation between sugar-sweetened beverage (SSB) consumption (sodas and fruit drinks) and dyslipidemia. There is limited evidence linking SSB consumption to emerging features of dyslipidemia, which can be characterized by variation in lipoprotein particle size, remnant-like particle (RLP), and apolipoprotein concentrations.
To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults.
We examined participants from the Framingham Offspring Study (FOS; 1987–1995, n = 3047) and the Women’s Health Study (1992, n = 26,218). Concentrations of plasma LDL cholesterol, apolipoprotein B (apoB), HDL cholesterol, apolipoprotein A1 (apoA1), triglyceride (TG), and non–HDL cholesterol, as well as total cholesterol:HDL cholesterol ratio and apoB:apoA1 ratio, were quantified in both cohorts; concentrations of apolipoprotein E, apolipoprotein C3, RLP-TG, and RLP cholesterol (RLP-C) were measured in the FOS only. Lipoprotein particle sizes were calculated from nuclear magnetic resonance signals for lipoprotein particle subclass concentrations (TG-rich lipoprotein particles [TRL-Ps]: very large, large, medium, small, and very small; LDL particles [LDL-Ps]: large, medium, and small; HDL particles [HDL-Ps]: large, medium, and small). SSB consumption was estimated from food frequency questionnaire data. We examined the associations between SSB consumption and all lipoprotein and apoprotein measures in linear regression models, adjusting for confounding factors such as lifestyle, diet, and traditional lipoprotein risk factors.
SSB consumption was positively associated with LDL cholesterol, apoB, TG, RLP-TG, RLP-C, and non–HDL cholesterol concentrations and total cholesterol:HDL cholesterol and apoB:apoA1 ratios; and negatively associated with HDL cholesterol and apoA1 concentrations (P-trend range: <0.0001 to 0.008). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes; lower concentrations of large LDL-Ps and medium HDL-Ps; and higher concentrations of small LDL-Ps, small HDL-Ps, and large TRL-Ps (P-trend range: <0.0001 to 0.001).
Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.
Elevated LDL Cholesterol with a Carbohydrate-Restricted Diet: Evidence for a "lean Mass Hyper-Responder" Phenotype
2022, Current Developments in Nutrition
People commencing a carbohydrate-restricted diet (CRD) experience markedly heterogenous responses in LDL cholesterol, ranging from extreme elevations to reductions.
The aim was to elucidate possible sources of heterogeneity in LDL cholesterol response to a CRD and thereby identify individuals who may be at risk for LDL cholesterol elevation.
Hypothesis-naive analyses were conducted on web survey data from 548 adults consuming a CRD. Univariate and multivariate regression models and regression trees were built to evaluate the interaction between body mass index (BMI) and baseline lipid markers. Data were also collected from a case series of five clinical patients with extremely high LDL cholesterol consuming a CRD.
BMI was inversely associated with LDL cholesterol change. Low triglyceride (TG) to HDL cholesterol ratio, a marker of good metabolic health, predicted larger LDL cholesterol increases. A subgroup of respondents with LDL cholesterol ≥200 mg/dL, HDL cholesterol ≥80 mg/dL, and TG ≤70 mg/dL were characterized as “lean mass hyper-responders.” Respondents with this phenotype (n = 100) had a lower BMI and, remarkably, similar prior LDL cholesterol versus other respondents. In the case series, moderate reintroduction of carbohydrate produced a marked decrease in LDL cholesterol.
These data suggest that, in contrast to the typical pattern of dyslipidemia, greater LDL cholesterol elevation on a CRD tends to occur in the context of otherwise low cardiometabolic risk.
Addition of oat bran reduces HDL-C and does not potentialize effect of a low-calorie diet on remission of metabolic syndrome: A pragmatic, randomized, controlled, open-label nutritional trial
2019, Nutrition
It is unclear whether addition of soluble fiber to a low-calorie diet potentializes weight loss and amelioration of metabolic syndrome (MetS). The aim of this study was to analyze the effects of oat bran on prevalence of MetS and associated disorders.
A pragmatic, randomized controlled, 6-wk nutritional trial was carried out with 154 outpatients (mean age 47.6 ± 12.6 y of age). The intervention group (n = 83) received a low-calorie diet plus 40 g/d of oat bran; the control group (n = 71) received a low-calorie diet only. MetS parameters and prevalence were calculated and compared (using two-tailed statistical tests) before and after follow-up.
After follow-up, a significant but similar reduction was observed in MetS prevalence (40% reduction, 63% and 64.8% prevalence in intervention and control groups, respectively; P = 0.226), body mass index, body weight, waist circumference, systolic and diastolic blood pressures, triacylglycerides, and blood glucose levels in both groups (P < 0.05). Mean high-density lipoprotein cholesterol (HDL-C) was reduced in the intervention group (43.6 ± 9.6 to 41.2 ± 9.5 mg/dL; P = 0.025), but not in the control group (44.6 ± 10.5 to 44.5 ± 12.1 mg/dL; P = 0.890). There was no significant difference in any of the variables between the groups, although the P-value for HDL-C was almost significant (P = 0.078). Calorie and dietetic fiber intake during the 6-wk period were similar in both groups.
Daily consumption of oat bran did not potentialize the beneficial effects of a traditional low-calorie diet on the prevalence of MetS and associated disorders. Additionally, it reduced HDL-C.
Weight loss is a critical factor to reduce inflammation
2018, Clinical Nutrition ESPEN
Chronic inflammation is a process sustained by the augmentation of circulating cytokines level and C-reactive protein (CRP). Adipocytes and adipose tissue infiltration with inflammatory cells, are an important source of adipokines production, and their expansion due to overnutrition is responsible for increased in inflammation. The reduction of body fat following both controlled diets or gastric surgery can be favorable in the reduction of pro-inflammatory cytokines.
A systematic literature search performed using PubMed, Google Scholar and Cochrane Library database screened for clinical and randomized controlled trials (RCTs) using the combination of the following keywords: “weight loss, inflammation,” “restricted diet, anti-inflammatory effect.” Studies including diet intervention, weight loss after gastric surgery have been included. Multidisciplinary program with the addition of food supplements, exercise, or drugs have been excluded to avoid their interference with the regulation inflammatory markers.
Out of 967 articles found, 76 were selected, including a total of 6742 patients with a mean age of 44.0 ± 3,3 years and a BMI of 33 ± 6.6. The observation period ranged from 3 weeks up to two years with an average weight loss per month of 1.1 kg. In most of the studies, it was found that weight loss caused a significant reduction of plasma level of inflammatory cytokines although three studies did not see any effect.
In obese and overweight subjects weight loss, induced both by energy-restricted diet or surgery, is a determinant factor for reducing the level of pro-inflammatory markers. Hypocaloric diet has an anti-inflammatory effect independent of the diet composition which can play an important role in the prevention of chronic diseases.

View all citing articles on Scopus

: Supported by funding from the Veterans Affairs Healthcare Network Competitive Pilot Project Grant.

View full text

A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity

Purpose

Methods

Results

Conclusion

Section snippets

Methods

Results

Discussion

Acknowledgment

Contin Educ

J Lipid Res

J Am Coll Cardiol

Am Heart J

LDL particle size in relation to insulin, proinsulin, and insulin sensitivityThe Insulin Resistance Atherosclerosis Study

Diabetes Care

Low-density lipoprotein particle size, central obesity, cardiovascular fitness, and insulin resistance syndrome markers in obese youths

Int J Obes Relat Metab Disord

Low carbohydrate as compared to low fat diet in severe obesity

N Engl J Med

A multi-center, randomized, controlled trial of a low-carbohydrate diet for obesity

N Engl J Med

Measurement issues related to lipoprotein heterogeneity

Am J Cardiol

Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women

Circulation

Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men

Circulation

Chronic subclinical inflammation as part of the insulin resistance syndromethe Insulin Resistance Atherosclerosis Study (IRAS)

Circulation

Markers of chronic inflammation and obesitya prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention

Int J Obes Relat Metab Disord

Weight loss reduces C-reactive protein levels in obese postmenopausal women

Circulation