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Low-carbohydrate diets impair flow-mediated dilatation: Evidence from a systematic review and meta-analysis

Letter to the Editor
Low-carbohydrate diets impair flow-mediated dilatation: evidence
from a systematic review and meta-analysis
With great interest, we read the meta-analysis of Bueno
et al.
‘Very-low-carbohydrate ketogenic diet v. low-fat diet
for long-term weight loss: a meta-analysis of randomised con-
trolled trials’, published ahead of print in the British Journal
of Nutrition
. In their article, the authors compared the
effects of very-low-carbohydrate (VLC) diets v. low-fat (LF)
diets on the biomarkers of obesity and their associated dis-
orders. With respect to different outcomes between both
the regimens, VLC diets turned out to be more effective in
lowering body weight, TAG levels and diastolic blood press-
ure and in increasing HDL-cholesterol levels. However, one
established risk factor of CVD, i.e. LDL-cholesterol, still
turned out to be harmfully affected by the VLC regimen,
most probably attributable to the larger amounts of saturated
fat in the diet
. In their discussion, the authors stated that
future meta-analyses should investigate the impact of low
carbohydrates (LC) v. LF on other important pathological
markers, e.g. endothelial function, in order to further assess
the safety of LC dietary therapies. This is reasonable, since
evidence from prospective cohort studies has shown that
endothelial dysfunction represents an independent risk
factor for the development of many CVD including athero-
. We, therefore, carried out a meta-analysis to com-
pare the effects of LC and LF regimens on flow-mediated
dilatation (FMD). FMD of the brachial artery is a non-invasive
measure of endothelial function, furthermore reflecting the
local bioavailability of endothelium-derived vasodilators,
especially NO. Inflammation of the endothelium is regarded
to play a major role in the destabilisation of atherosclerotic
lesions, therefore paving the way for future CVD events
A literature search was performed using the electronic data-
bases MEDLINE (until April 2013), EMBASE (until April
2013) and the Cochrane Trial Register (until April 2013),
with restrictions to randomised controlled trials, but no
restriction to language using the following search terms:
low fat diet AND endothelial function and low carbohydrate
diet AND endothelial function (Supplementary material, avail-
able online). Studies were included in the meta-analysis if they
met all of the following criteria: (1) randomised controlled
design with a minimum intervention period of 3 weeks;
(2) comparing a LC diet (# 45 % carbohydrates of total
energy content, TEC) with a LF diet (# 30 % fat of TEC)
(3) report of post-intervention values with standard devi-
ations; when the results of a study were published more
than once, only the most recent or most complete article
was included in the analysis; (4) participants age . 18 years;
(5) exclusion of subjects with CHD.
A meta-analysis was carried out in order to determine
the pooled effect of the intervention in terms of weighted
mean differences (WMD) between the post-intervention
values of the LC group and those of the LF group. All data
were analysed using the Review Manager 5.1 software, pro-
vided by the Cochrane Collaboration (http://ims.cochrane.
org/revman). Overall, six trials with a sample size of 210
subjects were included
(4 9)
. Study duration ranged between
3·5 weeks and 12 months. Decreases in FMD (WMD: 2 1·01
(95 % CI 2 1·83, 2 0·19) %, P¼ 0·02) were significantly more
pronounced following consumption of LC diets than following
that of LF diets (Fig. 1). The I
test showed very low hetero-
geneity (I
¼ 10 %).
Study or subgroup
SD Total Mean SD Total
Mean difference
(95 % CI)
Mean difference
IV, random, 95 % CI
Buscemi et al.
de Roos et al.
Phillips et al.
Varady et al.
Volek et al.
Wycherley et al.
Total (95 % CI)
Heterogeneity: t
= 0·11; c
= 5·56, df = 5 (P = 0·35); I
= 10 %
Test for overall effect: Z = 2·41 (P = 0·02)
0·40 (–4·00, 4·80)
–0·67 (–2·06, 0·72)
–1·90 (–4·01, 0·21)
–2·90 (–4·98, –0·82)
–0·60 (–2·31, 1·11)
–0·20 (–1·90, 1·50)
107 103 100·0 –1·01 (–1·83, –0·19)
–4 –2 0
Fig. 1. Forest plot showing pooled weighted mean differences (WMD) with 95 % CI for flow-mediated dilatation (%) of six randomised controlled low-carbohydrate
diet studies. For each low-carbohydrate trial,
represents the point estimate of the intervention effects. The horizontal line joins the lower and upper limits of the
95 % CI of these effects. The area of
reflects the relative weight of the study in the respective meta-analysis. At the bottom of the graph, represents the
pooled WMD with 95 % CI.
British Journal of Nutrition, page 1 of 2
q The Authors 2013
British Journal of Nutrition
In our meta-analysis, LC dietary protocols were associated
with a significant decrease in FMD when compared with
their LF counterparts. A recent meta-analysis of observational
studies including a sample size of 5·547 subjects has observed
that a 1 % decrease in FMD is associated with a 13 % increase
in the risk of future cardiovascular events
. In another recent
meta-analysis of cohort studies carried out by Noto et al.
an association between LC diets and increased risk of all-cause
mortality could be observed, although not for cardiovascular
(CVD) mortality as well as CVD incidence
. It should be
noted that in direct comparison with the meta-analysis carried
out by Bueno et al.
, we had to modify the inclusion criteria,
since only a few dietary intervention trials had reported FMD
as an outcome parameter. However, in consideration of the
fact that LC was associated with a higher all-cause mortality
risk, further trials are required to confirm the mechanisms of
FMD impairment following LC regimens.
Supplementary material
To view the supplementary material for this article, please visit
Lukas Schwingshackl
Georg Hoffmann
Department of Nutritional Sciences,
Faculty of Life Sciences, University of Vienna,
Althanstreet 14 UZA II, A-1090 Vienna,
1. Bueno NB, de Melo IS, de Oliveira SL, et al. (2013) Very-low-
carbohydrate ketogenic diet v. low-fat diet for long-term
weight loss: a meta-analysis of randomised controlled
trials. Br J Nutr (Epublication ahead of print version 7 May
2. Inaba Y, Chen JA & Bergmann SR (2010) Prediction of future
cardiovascular outcomes by flow-mediated vasodilatation of
brachial artery: a meta-analysis. Int J Cardiovasc Imaging 26,
3. Hu T, Mills KT, Yao L, et al. (2012) Effects of low-
carbohydrate diets versus low-fat diets on metabolic risk
factors: a meta-analysis of randomized controlled clinical
trials. Am J Epidemiol 176, Suppl. 7, S44S54.
4. Buscemi S, Verga S, Tranchina MR, et al. (2009) Effects of
hypocaloric very-low-carbohydrate diet vs. Mediterranean
diet on endothelial function in obese women. Eur J Clin
Invest 39, 339 347.
5. de Roos NM, Bots ML, Siebelink E, et al. (2001) Flow-
mediated vasodilation is not impaired when HDL-cholesterol
is lowered by substituting carbohydrates for monounsatu-
rated fat. Br J Nutr 86, 181188.
6. Phillips SA, Jurva JW, Syed AQ, et al. (2008) Benefit of
low-fat over low-carbohydrate diet on endothelial health in
obesity. Hypertension 51, 376382.
7. Varady KA, Bhutani S, Klempel MC, et al. (2011) Improve-
ments in vascular health by a low-fat diet, but not a
high-fat diet, are mediated by changes in adipocyte biology.
Nutr J 10,8.
8. Volek JS, Ballard KD, Silvestre R, et al. (2009) Effects of
dietary carbohydrate restriction versus low-fat diet on
flow-mediated dilation. Metabolism 58, 17691777.
9. Wycherley TP, Brinkworth GD, Keogh JB, et al. (2010) Long-
term effects of weight loss with a very low carbohydrate and
low fat diet on vascular function in overweight and obese
patients. J Intern Med 267, 452 461.
10. Noto H, Goto A, Tsujimoto T, et al. (2013) Low-carbohydrate
diets and all-cause mortality: a systematic review and meta-
analysis of observational studies. PLOS ONE 8, e55030.
L. Schwingshackl and G. Hoffmann2
British Journal of Nutrition
... Endothelial dysfunction and reduced vasodilatation have been identified as an early feature of atherosclerosis. Both are linked to high levels of LDL (Schwingshackl and Hoffmann, 2013) and hyperglycemia (Kawano et al., 1999). Low-carbohydrate diets have been associated with a significant decrease in FMD when compared to a low-fat diet (Varady et al., 2011). ...
... No changes in FMD were seen after the intervention in our young healthy participants. Previous studies among dyslipidemic, overweight and obese individuals have shown a decrease in FMD after a LCHF diet (Schwingshackl and Hoffmann, 2013). Overweight and obese participants often have underlying conditions that have taken years to develop. ...
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Low-carbohydrate-high-fat (LCHF) diets are efficient for weight loss, and are also used by healthy people to maintain bodyweight. The main aim of this study was to investigate the effect of 3-week energy-balanced LCHF-diet, with >75 percentage energy (E%) from fat, on glucose tolerance and lipid profile in normal weight, young, healthy women. The second aim of the study was to investigate if a bout of exercise would prevent any negative effect of LCHF-diet on glucose tolerance. Seventeen females participated, age 23.5 ± 0.5 years; body mass index 21.0 ± 0.4 kg/m2, with a mean dietary intake of 78 ± 1 E% fat, 19 ± 1 E% protein and 3 ± 0 E% carbohydrates. Measurements were performed at baseline and post-intervention. Fasting glucose decreased from 4.7 ± 0.1 to 4.4 mmol/L (p < 0.001) during the dietary intervention whereas fasting insulin was unaffected. Glucose area under the curve (AUC) and insulin AUC did not change during an OGTT after the intervention. Before the intervention, a bout of aerobic exercise reduced fasting glucose (4.4 ± 0.1 mmol/L, p < 0.001) and glucose AUC (739 ± 41 to 661 ± 25, p = 0.008) during OGTT the following morning. After the intervention, exercise did not reduce fasting glucose the following morning, and glucose AUC during an OGTT increased compared to the day before (789 ± 43 to 889 ± 40 mmol/L∙120min–1, p = 0.001). AUC for insulin was unaffected. The dietary intervention increased total cholesterol (p < 0.001), low-density lipoprotein (p ≤ 0.001), high-density lipoprotein (p = 0.011), triglycerides (p = 0.035), and free fatty acids (p = 0.021). In conclusion, 3-week LCHF-diet reduced fasting glucose, while glucose tolerance was unaffected. A bout of exercise post-intervention did not decrease AUC glucose as it did at baseline. Total cholesterol increased, mainly due to increments in low-density lipoprotein. LCHF-diets should be further evaluated and carefully considered for healthy individuals.
... Previous studies demonstrated an amelioration of glucose metabolism and endothelial function, measured as flow-mediated dilation (FMD), in obese patients after VLCKD; however, the results are still conflicting about the effects on FMD [4][5][6][7][8][9][10]. ...
... We did not observe a significant variation in FMD mean values. Although most previous studies in obese subjects reported a significant improvement in FMD after VLCKD [8,9], a meta-analysis conducted by Schwingshackl et al. [10] reported a significant impairment. The lack of statistical significance in our results prevents us from supporting one of these two hypotheses; this might be attributable to the short duration of the observation (four to five weeks). ...
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A very low carbohydrate ketogenic diet (VLCKD) is an emerging technique to induce a significant, well-tolerated, and rapid loss of body weight in morbidly obese patients. The low activity of lysosomal acid lipase (LAL) could be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is a common feature in morbidly obese patients. Fifty-two obese patients suitable for a bariatric surgery intervention underwent a 25-day-long VLCKD. The biochemical markers of glucose and lipid metabolism, and flow-mediated dilation (FMD) of the brachial artery were measured before and after VLCKD. LAL activity was measured using the dried blood spot technique in 20 obese patients and in a control group of 20 healthy, normal-weight subjects. After VLCKD, we observed a significant reduction in body mass index, fasting glucose, insulinemia, and lipid profile parameters. No significant variation in FMD was observed. The number of patients with severe liver steatosis significantly decreased. LAL activity significantly increased, although the levels were not significantly different as compared to the control group. In conclusion, VLCKD induces the activity of LAL in morbidly obese subjects and reduces the secretion of all circulating lipoproteins. These effects could be attributed to the peculiar composition of the diet, which is particularly poor in carbohydrates and relatively rich in proteins.
... Low-carbohydrate diets may also negatively impact artery function [137,138], indicative of oxidative stress and inflammation [139]. Additionally, preliminary data suggest that an Atkins diet, characterized by very high animal protein intake, significantly reduced myocardial perfusion and increased hs-CRP and lipoprotein(a) over the course of 1 year in those with CVD [140]. ...
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Obesity affects over one-third of Americans and increases the risk of cardiovascular disease and type II diabetes. Interventional trials have consistently demonstrated that consumption of plant-based diets reduces body fat in overweight and obese subjects, even when controlling for energy intake. Nonetheless, the mechanisms underlying this effect have not been well-defined. This review discusses six major dietary mechanisms that may lead to reduced body fat. These include (1) reduced caloric density, (2) improved gut microbiota symbiosis, (3) increased insulin sensitivity, (4) reduced trimethylamine-N-oxide (TMAO), (5) activation of peroxisome proliferator-activated receptors (PPARs), and (6) over-expression of mitochondrial uncoupling proteins. Collectively, these factors improve satiety and increase energy expenditure leading to reduced body weight.
... Specifically, it is unknown whether a reduction in dietary sugars alone, at weight stability, may be more beneficial to women. Such investigations should include a comprehensive assessment of vascular health including measures of arterial stiffness, endothelial function, and microvascular reactivity because the use of a CRD to reduce cardiovascular risk may improve some outcomes, but worsen others (Jovanovski et al., 2015;Schwingshackl and Hoffmann, 2013). In this regard, recent data from the Framingham Heart Study suggest that microvascular function contributes to the relation between aortic stiffness and cardiovascular events (Cooper et al., 2016). ...
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Increased aortic stiffness, measured by carotid-to-femoral pulse wave velocity (PWV), is an independent predictor of cardiovascular disease (CVD) and past data have shown that low-fat and low-energy diets, fed for 8-24 wks lower PWV. The purpose of this study was to determine whether a reduction in PWV would be achieved by dietary carbohydrate (CHO) restriction, shown to bring about weight loss over a shorter timeframe. Men [n=10, age: 41.8 ± 3.2 y, BMI: 34.2 ± 1.0 kg/m2 (mean±SE)] and women (n=10, age: 38.6 ± 1.9 y, BMI: 33.5 ± 1.2 kg/m2) with characteristics of insulin resistance and the metabolic syndrome, consumed a structured, CHO-restricted diet (CRD) for 4 wks (energy deficit, 645 kcal/d). For the whole group, subjects lost 5.4 ± 0.5 % (P<0.001) of body weight and experienced significant reductions in blood pressure (6-8%), plasma insulin (34%) and triglycerides (34%). PWV was reduced by 6 ± 2% (7.1 ± 0.2 m/s to 6.7 ± 0.2 m/s, P=0.008) and surprisingly, in women, it fell significantly (from 7.2 ± 0.3 m/s to 6.3 ± 0.3 m/s, P=0.028), while no changes were observed in men (7.2 ± 0.3 vs 7.0 ± 0.3 m/s, P=0.144). This is the first study to demonstrate that weight loss can improve PWV in as little as 4 wks and that dietary CHO restriction may be an effective treatment for reducing aortic stiffness in women. Future studies are needed to establish the mechanisms by which dietary CHO restriction may confer more cardiovascular benefits to women compared to men.
... 10,50 Individual studies that combine regular exercise with either unrestricted or energy-restricted low-carbohydrate diets have observed similar weight loss to our intervention at 6 months: 12.0 (95% CI ± 1.8) kg; 51 and at 1 year: 10.9 (95% CI ± 1.2) kg, 52 and 12.2 (includes telemonitoring, 95% CI ± 1.3) kg reductions. 53 However, studies on the effects of low-carbohydrate diets have shown higher rates of all-cause mortality, 54 decreased peripheral flow-mediated dilation, 55 worsening of coronary artery disease, 56 and increased rates of constipation, headache, halitosis, muscle cramps, general weakness and rash. 10 Other energy-restricted diets can be effective for weight loss, for example, one study using a 1 500 kcal daily intake, with 50% carbohydrate, 30% fat and 20% protein achieved an average 17.3 (95% CI ± 1.6) kg reduction in weight at 36 weeks, which is significantly more than our results. ...
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Background/Objective There is little randomised evidence using a whole food plant-based (WFPB) diet as intervention for elevated body mass index (BMI) or dyslipidaemia. We investigated the effectiveness of a community-based dietary programme. Primary end points: BMI and cholesterol at 6 months (subsequently extended). Subjects Ages 35–70, from one general practice in Gisborne, New Zealand. Diagnosed with obesity or overweight and at least one of type 2 diabetes, ischaemic heart disease, hypertension or hypercholesterolaemia. Of 65 subjects randomised (control n=32, intervention n=33), 49 (75.4%) completed the study to 6 months. Twenty-three (70%) intervention participants were followed up at 12 months. Methods All participants received normal care. Intervention participants attended facilitated meetings twice-weekly for 12 weeks, and followed a non-energy-restricted WFPB diet with vitamin B12 supplementation. Results At 6 months, mean BMI reduction was greater with the WFPB diet compared with normal care (4.4 vs 0.4, difference: 3.9 kg m⁻² (95% confidence interval (CI)±1), P<0.0001). Mean cholesterol reduction was greater with the WFPB diet, but the difference was not significant compared with normal care (0.71 vs 0.26, difference: 0.45 mmol l⁻¹ (95% CI±0.54), P=0.1), unless dropouts were excluded (difference: 0.56 mmol l⁻¹ (95% CI±0.54), P=0.05). Twelve-month mean reductions for the WFPB diet group were 4.2 (±0.8) kg m⁻² BMI points and 0.55 (±0.54, P=0.05) mmol l⁻¹ total cholesterol. No serious harms were reported. Conclusions This programme led to significant improvements in BMI, cholesterol and other risk factors. To the best of our knowledge, this research has achieved greater weight loss at 6 and 12 months than any other trial that does not limit energy intake or mandate regular exercise.
... The study showed that in overweight and obese patients with T2DM who participated in a one-year lifestyle modification program, compared to a traditional HighCHO diet, a LowCHO diet did not affect FMD. Conversely, previous studies [5,7] and a metaanalysis [6] have reported compared to a HighCHO diet, a verylow carbohydrate diet exerts detrimental effects on FMD. The exact reason for this discrepancy is not entirely clear, but unlike the present study, the very-low carbohydrate diets used previously have been high in saturated fat, which has been previously shown to adversely alter FMD [8]. ...
Background and aims: Very-low carbohydrate diets can improve glycaemic control in patients with type 2 diabetes (T2DM). However, compared to traditional higher carbohydrate, low fat (HighCHO) diets, they have been associated with impaired endothelial function (measured by flow mediated dilatation [FMD]) that is possibly related to saturated fat. This study aimed to examine the effects of a 12-month hypocaloric very-low carbohydrate, low saturated fat (LowCHO) diet compared to an isocaloric HighCHO diet. Methods: One hundred and fifteen obese patients with T2DM (age:58.4 ± 0.7 [SEM] yr, BMI:34.6 ± 0.4 kg/m(2), HbA1c:7.33 [56.3 mmol/mol] ± 0.10%) were randomised to consume an energy restricted LowCHO diet (Carb:Pro:Fat:Sat-Fat 14:28:58: < 10% energy; n = 58) or isocaloric HighCHO diet (53:17:30: < 10%; n = 57) whilst undertaking exercise (60 min, 3/wk). Bodyweight, HbA1c and FMD were assessed. Results: Seventy eight participants completed the intervention (LowCHO = 41, HighCHO = 37). Both groups experienced similar reductions in weight and HbA1c (-10.6 ± 0.7 kg, -1.05 ± 0.10%; p < 0.001 time, p ≥ 0.48 time × diet). FMD did not change (p = 0.11 time, p = 0.20 time × diet). Conclusions: In patients with obesity and T2DM, HighCHO diet and LowCHO diet have similar effects on endothelial function.
What does the best available balance of scientific evidence show is the optimum way to lose weight? Calorie density, water content, protein source, and other components significantly influence the effectiveness of different dietary regimes for weight loss. By “walling off your calories,” preferentially deriving your macronutrients from structurally intact plant foods, some calories remain trapped within indigestible cell walls, which then blunts the glycemic impact, activates the ileal brake, and delivers prebiotics to the gut microbiome. This may help explain why the current evidence indicates that a whole food, plant-based diet achieves greater weight loss compared with other dietary interventions that do not restrict calories or mandate exercise. So, the most effective diet for weight loss appears to be the only diet shown to reverse heart disease in the majority of patients. Plant-based diets have also been found to help treat, arrest, and reverse other leading chronic diseases such as type 2 diabetes and hypertension, whereas low-carbohydrate diets have been found to impair artery function and worsen heart disease, the leading killer of men and women in the United States. A diet centered on whole plant foods appears to be a safe, simple, sustainable solution to the obesity epidemic.
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Introduction Obesity is a nutritional disease which is still a health burden particularly in Jakarta. The main treatment for obesity is nutritional intervention. Nowadays, several dietary approaches have been developed, including ketogenic diet, which is still controversial. Methods Literature search had been done within 4 databases including PubMed®, Cochrane®, Google® Scholar, and Science Direct®, using keywords: obesity, ketogenic diet, low-fat diet, and weight loss. Then, Medical Sub Heading (MeSH) was used. The search resulted in two articles which were appraised according to aspects of validity, importance, and applicability Results A randomized-controlled trial study showed similar effect of weight loss with ketogenic diet compared to low-fat diet. On the other hand, a meta-analysis study showed ketogenic diet caused more weight loss than low-fat diet. Both studies showed an increased risk of cardiovascular disease from the ketogenic diet group, which were shown by a decrease of flow-mediated dilatation and an increase of LDL-C. Conclusion Ketogenic diet shows a better long-term effect for weight loss in obese patients than low-fat diet. However, ketogenic diet may increase the cardiovascular event risk significantly.
Full-text available
Introduction Obesity is a nutritional disease which is still a health burden particularly in Jakarta. The main treatment for obesity is nutritional intervention. Nowadays, several dietary approaches have been developed, including ketogenic diet, which is still controversial. Methods Literature search had been done within 4 databases including PubMed®, Cochrane®, Google® Scholar, and Science Direct®, using keywords: obesity, ketogenic diet, low-fat diet, and weight loss. Then, Medical Sub Heading (MeSH) was used. The search resulted in two articles which were appraised according to aspects of validity, importance, and applicability Results A randomized-controlled trial study showed similar effect of weight loss with ketogenic diet compared to low-fat diet. On the other hand, a meta-analysis study showed ketogenic diet caused more weight loss than low-fat diet. Both studies showed an increased risk of cardiovascular disease from the ketogenic diet group, which were shown by a decrease of flow-mediated dilatation and an increase of LDL-C. Conclusion Ketogenic diet shows a better long-term effect for weight loss in obese patients than low-fat diet. However, ketogenic diet may increase the cardiovascular event risk significantly.
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The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30 % of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect, Scopus, LILACS, SciELO, and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was body weight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure, glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis, five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference - 0·91 (95 % CI - 1·65, - 0·17) kg, 1415 patients), TAG (weighted mean difference - 0·18 (95 % CI - 0·27, - 0·08) mmol/l, 1258 patients) and diastolic blood pressure (weighted mean difference - 1·43 (95 % CI - 2·49, - 0·37) mmHg, 1298 patients) while increased HDL-C (weighted mean difference 0·09 (95 % CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95 % CI 0·04, 0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the long term; hence, a VLCKD may be an alternative tool against obesity.
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OBJECTIVE: Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence. DATA SOURCES: MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and for relevant articles published as of September 2012. Cohort studies of at least one year's follow-up period were included. REVIEW METHODS: Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting. RESULTS: We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07-1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98-1.24) and 0.98 (0.78-1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results. CONCLUSION: Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.
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Low-fat (LF) and high-fat (HF) weight loss diets improve brachial artery flow-mediated dilation (FMD) in obese individuals, although results are conflicting. Moreover, the role that adipose tissue plays in mediating these diet-related effects are unknown. This study examined how modulations in FMD by HF and LF diets relate to changes in adipocyte parameters. Obese subjects (n = 17) were randomized to a HF diet (60% kcal as fat) or a LF diet (25% kcal as fat) for 6 weeks. Both groups were restricted by 25% of energy needs. Body weight decreased (P <0.05) in both groups (HF: -6.6 ± 0.5 kg, LF: -4.7 ± 0.6 kg). Fat mass and waist circumference were reduced (P <0.05) in the LF group only (-4.4 ± 0.3 kg; -3.6 ± 0.8 cm, respectively). FMD improved (P <0.05) in the LF group (7.4 ± 0.8% to 9.8 ± 0.8; 32% increase) and was impaired in the HF group (8.5 ± 0.6% to 6.9 ± 0.7; 19% reduction). Increases in plasma adiponectin (P <0.05, 16 ± 5%), and decreases in resistin (P <0.05, -26 ± 11%), were shown by the LF diet only. Greater decreases in leptin were observed with LF (-48 ± 9%) versus HF (-28 ± 12%) (P <0.05, diet × time). Increased FMD by the LF diet was associated with increased adiponectin, and decreased fat mass, waist circumference, leptin, and resistin. Beneficial modulations in vascular health by LF diets may be mediated by improvements in adipocyte parameters.
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Low-fat diets, in which carbohydrates replace some of the fat, decrease serum cholesterol. This decrease is due to decreases in LDL-cholesterol but in part to possibly harmful decreases in HDL-cholesterol. High-oil diets, in which oils rich in monounsaturated fat replace some of the saturated fat, decrease serum cholesterol mainly through LDL-cholesterol. We used these two diets to investigate whether a change in HDL-cholesterol would change flow-mediated vasodilation, a marker of endothelial function. We fed thirty-two healthy volunteers two controlled diets in a weeks' randomised cross-over design to eliminate variation in changes due to differences between subjects. The low-fat diet contained 59.7 % energy (en%) as carbohydrates and 25.7 en% as fat (7.8 en% as monounsaturates); the oil-rich diet contained 37.8 en% as carbohydrates and 44.4 en% as fat (19.3 en% as monounsaturates). Average (sd) serum HDL-cholesterol after the low-fat diet was 0.21 (sd 0.12) mmol/l (8.1 mg/dl) lower than after the oil-rich diet. Serum triacylglycerols were 0.22 (sd 0.28) mmol/l (19.5 mg/dl) higher after the low-fat diet than after the oil-rich diet. Serum LDL and homocysteine concentrations remained stable. Flow-mediated vasodilation was 4.8 (SD 2.9) after the low-fat diet and 4.1 (SD 2.7) after the oil-rich diet (difference 0.7 %; 95 % CI -0.6, 1.9). Thus, although the low-fat diet produced a lower HDL-cholesterol than the high-oil diet, flow-mediated vasodilation, an early marker of cardiovascular disease, was not impaired.
The effects of low-carbohydrate diets (≤45% of energy from carbohydrates) versus low-fat diets (≤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials. Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses. Data abstraction was conducted in duplicate by independent investigators. Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (2.7 mg/dL; 95% confidence interval: 0.8, 4.6), and low density lipoprotein cholesterol (3.7 mg/dL; 95% confidence interval: 1.0, 6.4), but a greater increase in high density lipoprotein cholesterol (3.3 mg/dL; 95% confidence interval: 1.9, 4.7) and a greater decrease in triglycerides (-14.0 mg/dL; 95% confidence interval: -19.4, -8.7). Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets. These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors. Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss. Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted.
We conducted a meta-analysis of observational studies which examined the association between flow-mediated dilatation (FMD) of brachial artery, a noninvasive measure of endothelial function, and future cardiovascular events. Electronic databases were searched using a predefined search strategy. Data was independently abstracted on study characteristics, study quality, and outcomes by two reviewers. The multivariate relative risks, adjusted for confounding factors, were calculated from individual studies and then pooled using random-effects models. Statistical heterogeneity was evaluated using I2 statistics. Subgroup analyses and meta-regression analyses were conducted to assess the robustness of the meta-analysis. Publication bias was examined with funnel plot analysis and Egger's test. Four population-based cohort studies and ten convenience-cohort studies, involving 5,547 participants, were included in the meta-analysis. The pooled relative risks of cardiovascular events per 1% increase in brachial FMD, adjusted for confounding risk factors, was 0.87 (95% CI, 0.83- 0.91). The significant associations between brachial FMD and cardiovascular events were consistent among all subgroups evaluated, suggesting the robustness of the meta-analysis. However, the presence of heterogeneity in study quality, the remaining confounding factors, and publication bias in the available literature prevent a definitive evaluation of the additional predictive value of brachial FMD beyond traditional cardiovascular risk factors. The meta-analysis of heterogeneous studies with moderate methodological quality suggested that impairment of brachial FMD is significantly associated with future cardiovascular events. Further prospective randomized trials are warranted to confirm the efficacy of the usage of brachial FMD in the management of cardiovascular diseases.
To compare the effects of an energy reduced very low carbohydrate, high saturated fat diet (LC) and an isocaloric high carbohydrate, low fat diet (LF) on endothelial function after 12 months. Forty-nine overweight or obese patients (age 50.0 +/- 1.1 years, BMI 33.7 +/- 0.6 kg m(-2)) were randomized to either an energy restricted ( approximately 6-7 MJ), planned isocaloric LC or LF for 52 weeks. Body weight, endothelium-derived factors, flow-mediated dilatation (FMD), adiponectin, augmentation index (AIx) and pulse wave velocity (PWV) were assessed. All data are mean +/- SEM. Weight loss was similar in both groups (LC -14.9 +/- 2.1 kg, LF -11.5 +/- 1.5 kg; P = 0.20). There was a significant time x diet effect for FMD (P = 0.045); FMD decreased in LC (5.7 +/- 0.7% to 3.7 +/- 0.5%) but remained unchanged in LF (5.9 +/- 0.5% to 5.5 +/- 0.7%). PWV improved in both groups (LC -1.4 +/- 0.6 m s(-1), LF -1.5 +/- 0.6 m s(-1); P = 0.001 for time) with no diet effect (P = 0.80). AIx and VCAM-1 did not change in either group. Adiponectin, eSelectin, tPA and PAI-1 improved similarly in both groups (P < 0.01 for time). Both LC and LF hypoenergetic diets achieved similar reductions in body weight and were associated with improvements in PWV and a number of endothelium-derived factors. However, the LC diet impaired FMD suggesting chronic consumption of a LC diet may have detrimental effects on endothelial function.
We previously reported that a carbohydrate-restricted diet (CRD) ameliorated many of the traditional markers associated with metabolic syndrome and cardiovascular risk compared with a low-fat diet (LFD). There remains concern how CRD affects vascular function because acute meals high in fat have been shown to impair endothelial function. Here, we extend our work and address these concerns by measuring fasting and postprandial vascular function in 40 overweight men and women with moderate hypertriacylglycerolemia who were randomly assigned to consume hypocaloric diets (approximately 1500 kcal) restricted in carbohydrate (percentage of carbohydrate-fat-protein = 12:59:28) or LFD (56:24:20). Flow-mediated dilation of the brachial artery was assessed before and after ingestion of a high-fat meal (908 kcal, 84% fat) at baseline and after 12 weeks. Compared with the LFD, the CRD resulted in a greater decrease in postprandial triacylglycerol (-47% vs -15%, P = .007), insulin (-51% vs -6%, P = .009), and lymphocyte (-12% vs -1%, P = .050) responses. Postprandial fatty acids were significantly increased by the CRD compared with the LFD (P = .033). Serum interleukin-6 increased significantly over the postprandial period; and the response was augmented in the CRD (46%) compared with the LFD (-13%) group (P = .038). After 12 weeks, peak flow-mediated dilation at 3 hours increased from 5.1% to 6.5% in the CRD group and decreased from 7.9% to 5.2% in the LFD group (P = .004). These findings show that a 12-week low-carbohydrate diet improves postprandial vascular function more than a LFD in individuals with atherogenic dyslipidemia.
Background Obesity is a cardiovascular risk factor associated with endothelial dysfunction, but the effect of different weight loss strategies on endothelial function is not known. The effect of diet on endothelial function in two hypocaloric diets, a very-low-carbohydrate diet (A) and a Mediterranean diet (M), was measured by brachial artery flow-mediated dilation (FMD). Design Using a longitudinal, randomized, open study design, subjects were engaged in a 2-month weight loss diet. FMD, inflammatory cytokines [interleukin-6 (IL-6) and tumour necrosis factor-α] and a marker of oxidative stress [8-iso-prostaglandin F2α (8-iso-PGF2α)] were measured in subjects on three occasions: before initiating the diet (T0), after 5–7 days of dieting (T5) and after 2 months of dieting (T60). The very short- and medium-term time points were established to discriminate respectively the effect of the diet itself (T5) from that of weight loss (T60). Twenty overweight/obese but otherwise healthy women (BMI: 27–34·9 kg m−2; age 30–50 years) completed the study. Results Group A lost more weight (mean ± SEM; −7·6 ± 0·8 kg) than group M (−4·9 ± 0·6 kg, P = 0·014) at T60. The FMD was not significantly different between the two groups at T0 (group A: 12·2 ± 2·9% vs. group B: 10·3 ± 2·3%, P = ns). In group A, FMD was significantly reduced at T5 and returned to baseline at T60; in group M, FMD increased at T5 and returned to baseline at T60 (P = 0·007 for diet × time interaction). Serum concentrations of IL-6 and 8-iso-PGF2α were not significantly different between the two groups at T0 and increased significantly at T5 only in group A (P < 0·001 and P < 0·005 respectively). Conclusion As endothelial dysfunction is known to be associated with acute cardiovascular events, this study suggests that the cardiovascular risk might be increased in the first days of a very-low-carbohydrate diet.
Obesity is associated with impaired endothelial-dependent flow-mediated dilation, a precursor to hypertension and atherosclerosis. Although dieting generally improves cardiovascular risk factors, the direct effect of different dietary strategies on vascular endothelial function is not known. The purpose of this study was to test the hypothesis that a low-fat (LF) diet improves endothelial function compared with an isocaloric low-carbohydrate (LC) diet. Obese (n=20; body mass index: 29 to 39; mean systolic blood pressure: 107 to 125 mm Hg) and otherwise healthy volunteers were randomly assigned to either the American Heart Association modeled LF (30% fat calories) diet or an isocaloric LC Atkins' style diet (20 g of carbohydrates) for 6 weeks (4-week weight loss and 2-week maintenance phase). Brachial flow-mediated dilation and dilation to nitroglycerin were measured with ultrasound using automated edge detection technology (baseline, week 2, and week 6). Blood pressure, weight loss, and cholesterol profiles were measured throughout the study. Weight loss was similar in LF (100+/-4 to 96.1+/-4 kg; P<0.001) and LC (95.4+/-4 to 89.7+/-4 kg; P<0.001) diets. Blood pressure decreased similarly in both groups (LF: 8/5 mm Hg; LC: 12/6 mm Hg) at 6 weeks. After 6 weeks, the percentage of flow-mediated dilation improved (1.9+/-0.8; P<0.05) in the LF diet but was reduced in the LC diet (-1.4+/-0.6; P<0.05) versus baseline. Dilation to nitroglycerin and lipid panels was similar at 0, 2, and 6 weeks. Despite similar degrees of weight loss and changes blood pressure, LF diets improved brachial artery flow-mediated dilation over LC diets. LF diets may confer greater cardiovascular protection than LC diets.