Khedidja
Mekki
*a,
Nassima
Bouzidi-bekada
a,
Abbou
Kaddous
b and
Malika
Bouchenak
a
aLaboratoire de Nutrition Clinique et Métabolique, Département de Biologie, Faculté des Sciences, Université d'Oran, 31100, Algeria. E-mail: khmekki@hotmail.com; Fax: +213 41 58 19 44; Tel: +213 41 58 19 44
bService de Néphrologie, Etablissement Hospitalo-Universitaire Oran, Algeria
First published on 22nd September 2010
Dyslipidemia, oxidative stress (OS) and inflammation increase the risk of cardiovascular disease in chronic renal failure (CRF) patients. The aim of this study was to evaluate the effect of nutritional advice on dyslipidemia and biomarkers in CRF patients. 40 CRF patients with dyslipidemia, hypertriglyceridemia and/or hypercholesterolemia were randomly assigned to either the control or the intervention group. The intervention group received nutritional advice adapted to a Mediterranean diet (MD). Patients were assessed at baseline (T0) and after 30 (T1), 60 (T2) and 90 (T3) days for dietary intake and biomarkers. In the intervention group compared to the control group, TG concentrations were decreased by 26% at T3 (p < 0.05), TC concentrations were diminished by 14% at T2 and by 35% at T3 (p < 0.05). A decrease in LDL-C was noted at T2 and T3 (p < 0.05). The TC/HDL-C ratio was diminished at T1, T2 and T3 (p < 0.05). The apo A-I/apo B ratio was elevated at T3 (p < 0.05). HDL-C, apo A-I, apo B concentrations and the TC/LDL-C ratio were similar in the both groups at T1, T2 and T3. Creatinine, urea, glomerular filtration rate (GFR), urate, iron and bilirubin values remained unchanged in both groups. Haemoglobin concentrations were elevated at T1 (p < 0.05). Increased albumin values were observed at T2 (p < 0.05). CRP concentrations were decreased by 29% at T1 (p < 0.05) and 40% (p < 0.01) at T3. Fibrinogen (p < 0.01) concentrations were decreased at T3. In the intervention group compared to control group (p < 0.01), TBARS values were decreased by 16% at T2 and 21% at T3 (p < 0.05). In this study, we demonstrate that the nutritional management of CRF patients before dialysis based on the MD improves food consumption, reduces dyslipidemia and protects against lipid peroxidation and inflammation, allowing patients to enter dialysis with an acceptable nutritional and cardiovascular state.
The increased prevalence of both CVD morbidity and mortality is evident at all ages among patients with CRF. Both traditional risk factors, including diabetes, dyslipidemia and hypertension, and non-traditional risk factors associated with CRF, including inflammation, oxidant stress and malnutrition, may further increase CVD risk.1–3
Dyslipidemia enhances lipid peroxidation and activates free radical reactions.2 Hypertriglyceridemia, hypercholesterolemia and elevated levels of low-density lipoprotein-cholesterol (LDL-C) are identified as key factors for CVD risk in CRF patients. Observational and epidemiological data have suggested the potential predictive role of C-reactive protein (CRP) in coronary heart disease.4–6
Beneficial outcomes can be strengthened through dietary interventions. Nutritional intervention plays a major role in preserving the overall well-being of CRF patients. In preparation for RRT, dietary monitoring aims to reduce cardiovascular risk factors, prevent malnutrition and slow the progression of renal disease,1–3 all of which can contribute to positive outcomes for patients. There are several potential advantages to prescribing a carefully designed low-protein diet (0.75 g kg−1 BW d−1) for the treatment of CRF patients.7 Low-protein diets reduce the generation of nitrogenous wastes and inorganic ions, which cause many of the clinical and metabolic characteristics of uremia. Moreover, low-protein diets can diminish the effects of hyperphosphatemia, metabolic acidosis, hyperkalemia and other electrolyte disorders that are the consequence of renal function loss.7
During the past decade, a large body of evidence has related the adherence to a Mediterranean diet (MD) to a decrease in all the causes of mortality, as well as the incidence of coronary heart diseases.8 An MD has long been recommended for its antiatherosclerotic properties.9 Among the effects of an MD diet, the suppression of lipoprotein peroxidation10 and the normalization of endothelial function are observed.11,12 Such diets do not need to be restricted in total lipid intake as long as there is no excess of energy intake over expenditure and vegetable oils are emphasized as the main source of lipids, which are low in saturated fats and partially hydrogenated oils.13 The traditional MD includes the high consumption of olive oil, legumes, unrefined cereals and cereal products (whole grain bread, pasta and brown rice), fruits and vegetables, the moderate to high consumption of fish and dairy products (cheese and yogurt), the low consumption of meat and meat products, and moderate wine consumption.14,15 The ratio of monounsaturated (MUFA) to saturated fats is much higher in the MD than in other places of the world, including northern Europe and North America.14,15
The aim of this study is to evaluate the effect of appropriate nutritional advice based on the MD, on feeding, dyslipidemia and biomarkers in dyslipidemic CRF patients. We hypothesize that nutritional management based on a healthy and varied diet will enhance food intake and reduce cardiovascular risk through an adjustment of dyslipidemia and biomarker abnormalities, suggesting that an MD diet may have a preventive role against CVD.
CRF patients | Control group | Intervention group | |
---|---|---|---|
a Data are expressed as mean ± standard error. BMI: body mass index (weight kg/height m2); SBP: systolic blood pressure; DBP: diastolic blood pressure. | |||
Patients (n) | 40 | 20 | 20 |
Age/years | 61 ± 14 | 59 ± 12 | 60 ± 10 |
Weight/kg | 74 ± 15 | 73 ± 11 | 76 ± 14 |
BMI | 26.2 ± 5.6 | 25.1 ± 4.2 | 26.9 ± 3.9 |
Sex ratio (M/F) | 22/18 | 10/10 | 11/9 |
Smokers (%) | 32 | 29 | 30 |
Employed (%) | 50 | 45 | 38 |
SBP/mm Hg | 125 ± 10 | 135 ± 8 | 128 ± 11 |
DBP/mmHg | 84 ± 1 | 80 ± 2 | 83 ± 2 |
Glucose/g L−1 | 0.90 ± 0.06 | 0.86 ± 0.01 | 0.95 ± 0.02 |
Triacylglycerols/mmol L−1 | 3.8 ± 0.1 | 3.2 ± 0.3 | 3.8 ± 0.1 |
Total cholesterol/mmol L−1 | 6.1 ± 0.7 | 6.5 ± 0.4 | 6.1 ± 0.7 |
To control the recommendation monitoring, nutritional surveys were carried out at baseline and at 30 (T1), 60 (T2) and 90 (T3) days after the beginning of nutritional intervention.
All patients received intervention instructions at the Nephrology ward of the University Hospital of Oran. The purpose of this study was explained to the subjects, and the investigation was carried out with their consent. The experimental protocol was approved by the Committee for Research on Human Subjects of Oran.
Triacylglycerols (TG) and total cholesterol (TC) were determined by colorimetric methods (BioMérieux Kits, France). Urea and creatinine were analyzed by colorimetric methods (Kits Biocon). Serum high-density lipoprotein-cholesterol (HDL-C) was determined enzymatically using a CHOD-PAP kit after precipitation of the chylomicrons, very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) with phosphotungstic acid and Mg2+ (BioMérieux Kits, SA-France). Serum LDL-C was determined enzymatically using a CHOD-PAP kit after precipitation of LDL. Serum apolipoproteins (apo) A-I and B were measured by the immunoturbidimetric method (Human kit, Allemagne). Serum lipid peroxidation was estimated by measuring the concentrations of thiobarbituric acid reactive substances (TBARS) according to the method of Quintanilha et al.,18 using tetramethoxypropane (Prolabo) as a precursor of malondialdehyde. C-Reactive Protein (CRP) was measured by the immunoturbidimetric method (Fumouze, France). Colorimetric methods were used for the determination of albumin, urate (Kits Boehringer, Mannheim, Germany), iron and bilirubin (Biolabo kits, France). Fibrinogen levels were measured using automatic nephelometry.
Baseline | Control group | Intervention group | DR | |||||
---|---|---|---|---|---|---|---|---|
T0 | T1 | T2 | T3 | T1 | T2 | T3 | ||
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. DR: dietary recommendations. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05. | ||||||||
TEI/MJ | 6.8 ± 0.3 | 6.0 ± 1.5 | 6.1 ± 0.3c | 6.1 ± 0.2c | 7.5 ± 0.6 | 7.9 ± 0.4d | 7.6 ± 0.1d | 8 |
Proteins/MJ | 0.6 ± 0.02 | 0.60 ± 0.1 | 0.6 ± 0.01 | 0.6 ± 0.04 | 0.6 ± 0.07 | 0.7 ± 0.09 | 0.7 ± 0.07 | 0.8 |
% of TEI | 8 | 9 | 9 | 9 | 9 | 9 | 10 | 10 |
Carbohydrates/MJ | 4.1 ± 0.1 | 4.2 ± 2.1 | 3.9 ± 0.2 | 3.3 ± 0.1c | 4.5 ± 0.2 | 4.3 ± 0.1 | 4.4 ± 0.1d | 4.4 |
% of TEI | 65 | 70 | 63 | 64 | 60 | 56b | 55b | 55 |
Lipids/MJ | 1.8 ± 0.1 | 1.3 ± 0.6 | 1.9 ± 0.2c | 1.9 ± 0.2 | 2.4 ± 0.2 | 2.7 ± 0.2d | 2.6 ± 0.3d | 2.8 |
% of TEI | 27 | 21 | 28 | 27 | 32 | 35d | 35d | 35 |
An improvement in animal protein intake (Table 3) was noted only at T3 in the intervention group compared to the controls and to T0 (p < 0.05). In parallel, the consumption of vegetable protein decreased at T1 and T3 compared to the controls (p < 0.05). An increase in sugar intake was noted at T2 and T3 (p < 0.05) in the intervention group compared to the control group. Starch consumption decreased at T3 in the intervention group compared to the control group and to T0 (p < 0.05). Fiber and cholesterol intakes were in accordance with nutritional requirements. PUFA and SFA intakes were, respectively, lowered and increased at T1, T2 and T3 in the intervention group compared to the control group (p < 0.05). An increase in MUFA intake was noted at T2 and T3 (p < 0.05). In the intervention group, a decrease was noted in PUFA intake at T1, T2 and T3 compared to T0 (p < 0.05).
Baseline | Control group | Intervention group | DR | |||||
---|---|---|---|---|---|---|---|---|
T0 | T1 | T2 | T3 | T1 | T2 | T3 | ||
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. DR: dietary recommendations. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05. | ||||||||
Animal (%) | 38 | 41 | 55 | 69 | 58c | 52 | 57d | 60 |
Vegetable (%) | 62 | 59 | 45 | 31 | 42b | 48c | 43d | 40 |
Sugar (%) | 18 | 20 | 19 | 21 | 25 | 30b | 29b | 40 |
Starch (%) | 82 | 80 | 81 | 79 | 75 | 70c | 61d | 60 |
Fiber/g | 36 | 35 | 30 | 29 | 35 | 34 | 33 | 30 |
PUFA (%) | 30 | 35 | 32 | 30 | 25d | 26d | 23d | 25 |
MUFA (%) | 37 | 36 | 35 | 33 | 38 | 44b | 49d | 50 |
SFA (%) | 33 | 29 | 23 | 37 | 37b | 30b | 28b | 25 |
Cholesterol/mg | 180 | 190 | 175 | 225 | 230 | 225 | 228 | <300 |
At T3, the qualitative distribution of nutrients had a tendency to be closer to the recommended diet. In the intervention group compared to the control group (Table 4), a high consumption of cooked vegetables, fruit, bread, cereals, rice, pasta, milk and dairy products was noted at T3 in the intervention group compared to the control group (p < 0.05). However, a significant decrease was noted in fat intake at T3 (p < 0.01) in the intervention group compared to the control group and to T0 (p < 0.05).
Food group | Baseline | Control group | Intervention group | DR | ||||
---|---|---|---|---|---|---|---|---|
T0 | T1 | T2 | T3 | T1 | T2 | T3 | ||
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. DR: dietary recommendations. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05. | ||||||||
Cooked vegetables and fruit | 255 ± 66 | 230 ± 15 | 238 ± 72 | 238 ± 65 | 262 ± 85 | 393 ± 108 | 462 ± 99d | 500 |
Bread, cereals, rice and pasta | 278 ± 55 | 270 ± 95 | 267 ± 56 | 298 ± 15 | 302 ± 26 | 326 ± 89 | 411 ± 85b | 400 |
Milk and dairy products | 85 ± 9 | 95 ± 14c | 99 ± 28c | 95 ± 12 | 121 ± 14c | 137 ± 14c | 160 ± 35d | 180 |
Meat, poultry and fish | 35 ± 12 | 32 ± 4.0 | 39 ± 23 | 45 ± 10 | 40 ± 0.64b | 48 ± 14 | 70 ± 25 | 50 |
Raw vegetables and fruits | 125 ± 26 | 130 ± 75 | 139 ± 13 | 167 ± 62 | 138 ± 15 | 198 ± 10d | 255 ± 92 | 50 |
Fat | 80 ± 12 | 85 ± 12 | 79 ± 32 | 95 ± 15 | 77 ± 25 | 45 ± 33 | 55 ± 0.75c | 60 |
Sweet products | 95 ± 18 | 87 ± 13 | 79 ± 8.6 | 89 ± 8 | 78 ± 22 | 69 ± 8.6 | 59 ± 16 | 60 |
Baseline | Control group | Intervention group | |||||
---|---|---|---|---|---|---|---|
T0 | T1 | T2 | T3 | T1 | T2 | T3 | |
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05. e p < 0.01. | |||||||
TG/mmol L−1 | 3.2 ± 0.3 | 2.8 ± 0. 6 | 3.0 ± 0.1 | 3.9 ± 0.1 | 3.4 ± 0.4 | 3.1 ± 0.8 | 2.9 ± 0.1d |
TC/mmol L−1 | 6.5 ± 0.4 | 5.3 ± 1.0 | 6.3 ± 1.0 | 5.4 ± 0.4 | 6.1 ± 0.02 | 5.4 ± 0.9b | 4.1 ± 0.5d |
HDL-C/mmol L−1 | 2.1 ± 0.5 | 2.7 ± 0.2 | 2.5 ± 0.2 | 3.0 ± 0.2 | 2.5 ± 0.2 | 2.5 ± 0.4 | 2.8 ± 0.6 |
LDL-C/mmol L−1 | 3.5 ± 1.0 | 3.3 ± 0.2 | 3.6 ± 0.2 | 3.0 ± 0.2 | 3.6 ± 0.2 | 2.8 ± 0.1b | 2.0 ± 0.02b,e |
Apo AI/g L−1 | 0.9 ± 0.2 | 1.2 ± 0.6 | 1.3 ± 0.6 | 1.3 ± 0.5 | 1.3 ± 0.1 | 1.1 ± 0.1 | 1.2 ± 0.1 |
Apo B/g L−1 | 0.9 ± 0.1 | 1.0 ± 0.2 | 1.0 ± 0.3 | 1.0 ± 0.1 | 1.1 ± 0.1 | 1.1 ± 0.3 | 1.0 ± 0.1 |
TC/HDL-C | 2.9 ± 0.1 | 2.6 ± 0.1 | 2.8 ± 0.2 | 2.7 ± 0.4 | 2.1 ± 0.2d | 1.8 ± 0.1d | 1.7 ± 0.2b,e |
TC/LDL-C | 2.1 ± 0.2 | 2.6 ± 0.8 | 2.3 ± 0.1 | 2.3 ± 0.4 | 2.8 ± 0.9 | 3.2 ± 0.1d | 2.1 ± 0.5 |
Apo AI/Apo B | 0.8 ± 0.1 | 1.5 ± 0.5 | 0.9 ± 0.1 | 1.1 ± 0.2 | 1.6 ± 0.4 | 0.8 ± 0.4 | 1.8 ± 0.1d |
Baseline | Control group | Intervention group | |||||
---|---|---|---|---|---|---|---|
T0 | T1 | T2 | T3 | T1 | T2 | T3 | |
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05. e p < 0.01. | |||||||
Creatinine/μmol mL−1 | 189.0 ± 70.0 | 150.0 ± 49.0 | 169.0 ± 49.0 | 110.0 ± 33.0 | 151.0 ± 57.0 | 170.0 ± 56.0 | 109.0 ± 47.0 |
Urea/mmol L−1 | 14.2 ± 4.8 | 12.0 ± 5.0 | 12.0 ± 2.1 | 11.8 ± 4.4 | 11.0 ± 4.8 | 11.5 ± 3.0 | 12.1 ± 3.4 |
GRF/mL L−1 | 75.0 ± 15.0 | 69.0 ± 9.0 | 72.0 ± 6.0 | 75.0 ± 8.0 | 70.0 ± 10.0 | 72.0 ± 6.0 | 77.0 ± 0.9 |
Urate/mmol L−1 | 0.4 ± 0.1 | 0.4 ± 0.1 | 0.4 ± 0.1 | 0.6 ± 0.2 | 0.6 ± 0.1 | 0.5 ± 0.1 | 0.6 ± 0.1 |
Iron/μmol L−1 | 33.0 ± 17.7 | 38.1 ± 15.0 | 35.0 ± 0.1 | 37.2 ± 0.8 | 36.0 ± 0.1 | 34.6 ± 0.1 | 35.1 ± 0.3 |
Bilirubin/μmol L−1 | 6.2 ± 2.6 | 5.6 ± 2.1 | 7.0 ± 0.1 | 8.1 ± 0. 7 | 7.3 ± 0.1 | 6.8 ± 1.3 | 7.6 ± 0.1 |
Haemoglobin/g dL−1 | 12.1 ± 0.1 | 10.0 ± 0.1c | 12.9 ± 0.1 | 14.1 ± 2.2 | 13.5 ± 0.1d | 13.9 ± 1.1 | 13.9 ± 5.0 |
Albumin/g L−1 | 32.2 ± 5.0 | 30.4 ± 6.0 | 35.0 ± 2.1 | 38.0 ± 10.0 | 38.0 ± 6.3 | 42.2 ± 5.0c | 44.1 ± 5.2 |
CRP/mg L−1 | 6.5 ± 0.9 | 7.0 ± 0.2 | 7.8 ± 0.8 | 7.0 ± 0.1 | 6.4 ± 0.1b | 5.8 ± 1.0 | 4.2 ± 0.2e |
Fibrinogen/g L−1 | 3.5 ± 0.7 | 3.0 ± 0.7 | 3.2 ± 1.9 | 3.4 ± 0.9 | 2.9 ± 0.5 | 2.9 ± 1.5 | 2.0 ± 0.1e |
TBARS/μmol L−1 | 8.4 ± 0.5 | 9.5 ± 0.2 | 8.0 ± 0.7 | 7.8 ± 0.3 | 7.9 ± 1.5 | 6.7 ± 0.3d | 6.3 ± 0.01d |
It has been shown that there is an association between elevated CRP levels and the risk of cardiovascular events and peripheral vascular disease that is independent of traditional risk factors.4–6 In our study, the CRP level was greater than 5 mg L−1 at the beginning of the study and then was modified by the diet. Elevated serum CRP levels are correlated with increased risk of death due to stroke.4 With levels of CRP above 5.5 mg L−1, the risk is 1.67-times higher than that at levels below 2.1 mg L−1; moreover, this is independent of other risk factors.4 In our patients, CRP concentrations were inversely associated with cooked vegetables, fruit and fish; fish being the best source of omega-3 fatty acids. Indeed, in our patients, sardines were the most frequently consumed fish (twice a week). A strong inverse relationship was found between fish consumption and levels of inflammatory markers related to CV.22 Similarly, it has been demonstrated that a greater adherence to a traditional MD is independently associated with a reduction in CRP and fibrinogen levels.21 The association between elevated plasma fibrinogen and coronary risk may also partly reflect an ongoing inflammatory process.27 However, the exact association between these proinflammatory markers and diet was not clear. Therefore, because fish consumption has been associated with decreased concentrations of these proinflammatory markers, it can be suggested that regular fish intake may suppress inflammation and have beneficial effects on human health. Recently, we also showed that omega-3 fatty acid supplementation (2.1 g day−1) was inversely associated with hypertriglyceridemia and CRP in CRF patients eating a balanced diet.20 Zampelas et al. (2005)22 suggested that the benefit is more pronounced if omega-3 fatty acids are consumed in the form of fish rather than in the form of a supplement.
In conclusion, the nutritional management of CRF patients before dialysis based on an MD improves food consumption, reduces dyslipidemia and protects against lipid peroxidation and inflammation, allowing patients to enter dialysis with an acceptable nutritional and cardiovascular state.
This journal is © The Royal Society of Chemistry 2010 |