Skip to main content Accessibility help


  • Access
  • Cited by 9


      • Send article to Kindle

        To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Nutritional management of hyperapoB
        Available formats

        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Nutritional management of hyperapoB
        Available formats

        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Nutritional management of hyperapoB
        Available formats
Export citation


Plasma apoB is a more accurate marker of the risk of CVD and type 2 diabetes (T2D) than LDL-cholesterol; however, nutritional reviews targeting apoB are scarce. Here we reviewed eighty-seven nutritional studies and present conclusions in order of strength of evidence. Plasma apoB was reduced in all studies that induced weight loss of 6–12 % using hypoenergetic diets (seven studies; 5440–7110 kJ/d; 1300–1700 kcal/d; 34–50 % carbohydrates; 27–39 % fat; 18–24 % protein). When macronutrients were compared in isoenergetic diets (eleven studies including eight randomised controlled trials (RCT); n 1189), the diets that reduced plasma apoB were composed of 26–51 % carbohydrates, 26–46 % fat, 11–32 % protein, 10–27 % MUFA, 5–14 % PUFA and 7–13 % SFA. Replacement of carbohydrate by MUFA, not SFA, decreased plasma apoB. Moreover, dietary enriching with n-3 fatty acids (FA) (from fish: 1·1–1·7 g/d or supplementation: 3·2–3·4 g/d EPA/DHA or 4 g/d EPA), psyllium (about 8–20 g/d), phytosterols (about 2–4 g/d) or nuts (30–75 g/d) also decreased plasma apoB, mostly in hyperlipidaemic subjects. While high intake of trans-FA (4·3–9·1 %) increased plasma apoB, it is unlikely that these amounts represent usual consumption. Inconsistent data existed on the effect of soya proteins (25–30 g/d), while the positive association of alcohol consumption with low plasma apoB was reported in cross-sectional studies only. Five isoenergetic studies using Mediterranean diets (including two RCT; 823 subjects) reported a decrease of plasma apoB, while weaker evidence existed for Dietary Approaches to Stop Hypertension (DASH), vegetarian, Nordic and Palaeolithic diets. We recommend using a Mediterranean dietary pattern, which also encompasses the dietary components reported to reduce plasma apoB, to target hyperapoB and reduce the risks of CVD and T2D.


Atherogenic lipoproteins are chylomicrons, VLDL, intermediate-density lipoproteins, LDL and lipoprotein (a) (Lp(a)). Each of these particles contains one molecule of apoB, which encircles the particle providing an external supportive skeleton within which the particle exists( 1 ). Since each particle contains one molecule of apoB, whether as apoB48 carried on intestinal chylomicron particles or apoB100 carried on hepatic lipoproteins, plasma apoB represents the number of all atherogenic apoB-lipoproteins. Of these, LDL make up by far the largest percentage (about 90 % on average), and therefore plasma apoB is driven by LDL apoB( 2 4 ). Plasma total cholesterol, non-HDL-cholesterol (non-HDL-C) and LDL-cholesterol (LDL-C) are all highly correlated with apoB and the risk of vascular disease increases exponentially as the concentrations of all four increase in plasma. However, the lipid content and therefore the size of all the apoB particles can vary substantially( 5 ).

In particular, LDL particles can contain an average mass of cholesterol or be cholesterol-enriched or cholesterol-depleted. When LDL particles are either cholesterol-enriched or cholesterol-depleted, LDL-C is an inaccurate measure of LDL number, particularly if plasma TAG is more than 1·5 mmol/l( 1 ). Hyperapobetalipoproteinaemia (or hyperapoB) was defined by Sniderman et al. ( 6 ) in 1980 as a proatherogenic lipoprotein phenotype characterised by elevated numbers of apoB-lipoproteins but normal or near-normal plasma LDL-C. In this phenotype, the discordance between the LDL-C and apoB is due to cholesterol-depleted LDL particles. Of note, in contrast to plasma TAG used for the calculation of LDL-C in the Friedewald equation, plasma apoB can be measured in non-fasting samples( 1 ). A plasma apoB of ≥1·2 g/l, which is about the 75th percentile of plasma apoB concentrations in a Canadian population( 7 ), identifies subjects with hyperapoB( 8 ).

Plasma apoB and CVD

Plasma apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C( 9 ). A recent meta-analysis, comparing the number of clinical events prevented by different treatment strategies, revealed that over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy( 9 ). The measurement of plasma apoB was recommended in 2009 by the American Association for Clinical Chemistry Lipoproteins and Vascular Diseases Division Working Group on Best Practices as a more reliable indicator of risk than LDL-C( 10 ). It was also introduced to the Canadian dyslipidaemia guidelines in the same year as an alternative primary target of therapy( 11 ) and continues to be recommended in the latest update of the guideline in 2014( 1 , 12 ). Particularly for subjects with intermediate CVD risk and/or insulin resistance, an apoB ≥1·2 g/l identifies patients at increased CVD risk who may benefit from pharmacotherapy despite a plasma LDL-C of <3·5 mmol/l( 1 ). Similarly in 2011, the European Atherosclerosis Society and European Society of Cardiology stated that non-HDL-C or apoB may better estimate the concentration of atherogenic particles than LDL-C, especially in high risk patients with diabetes or the metabolic syndrome( 13 ). The recent 2013 guidelines of the American College of Cardiology and the American Heart Association, however, do not encompass the use of plasma apoB for the screening and treatment target for CVD( 14 ). Since then a series of reports using discordance analysis have all shown that apoB is superior to either LDL-C or non-HDL-C to estimate cardiovascular risk( 15 , 16 ).

Plasma apoB and type 2 diabetes

Emerging clinical and epidemiological evidence also links hyperapoB to the development of type 2 diabetes (T2D), in addition to CVD, in humans. Both diseases are viewed as chronic inflammatory disease, and apoB-lipoproteins, primarily LDL, are known to induce multiple derangements in inflammatory cascades that lead to atherosclerosis( 17 , 18 ). However, evidence from our laboratory( 19 ), as well as others( 20 22 ), has shown that plasma apoB, not total cholesterol or LDL-C, correlates strongly with plasma inflammatory markers in human subjects. Moreover, in non-diabetic obese subjects, plasma apoB but not LDL-C correlates positively with dysfunctional white adipose tissue ex vivo and delayed plasma clearance of dietary fat, hyperinsulinaemia, insulin resistance and activation of the IL-1β system in vivo ( 19 , 23 25 ), all of which are known risk factors for T2D. Epidemiological studies support that hyperapoB predicts the development of T2D before the onset of the disease by 3–10 years in Turkish( 26 ), Canadian( 27 ), Finnish( 28 ) and South Korean( 29 ) populations, independent of traditional risk factors such as central adiposity( 26 , 27 ), inflammation( 26 ), fasting glucose and glycated Hb( 27 , 29 ).

Despite the central role of hyperapoB in the prediction and promotion of CVD and T2D and the inaccurate prediction of plasma apoB by lipids particularly in subjects with hyperlipidaemia, nutritional reviews and guidelines( 11 ) for the treatment of dyslipidaemias have not addressed the regulation of apoB-particle number in plasma and focused mainly on their lipid content. Moreover, recent reviews on this topic mainly focused on the effect of dietary fatty acids (FA) and weight loss on plasma apoB-lipoproteins( 30 32 ). Accordingly, we reviewed recent published literature (within the last 10 years) on the effects of multiple dietary interventions and components on plasma apoB and other parameters (VLDL-cholesterol (VLDL-C), LDL-C, non-HDL-C, TAG, apoA1 and apoB:apoA1). All human studies in an adult population (>18 years old) that were written in English and corresponded to the search criteria ‘diet and apoB’ on PubMed on 25 May 2015 were included. Genetic variations affecting plasma lipoprotein-related parameters are reported to affect the response efficiency to dietary interventions or components( 33 36 ). However, as the present review aims to guide nutritional interventions targeting hyperapoB in clinical practice where data on the genetic background may not be readily available, studies examining specific gene–diet interactions were not included in this analysis. Given that the definitions of very-low- to high-carbohydrate (CHO) diets differ between studies, we used the definitions suggested by Feinman et al. ( 37 ), mostly driven from the American Diabetic Association Guidelines, and unified the definitions for CHO intake throughout the eighty-seven studies examined. Very-low, low-, moderate- and high-CHO diets were those providing less than 10 %, 10–25 %, 26–45 % and >45 % of energy from CHO, respectively( 37 ). Special emphasis was placed on data generated from randomised controlled trials (RCT) to determine the strength of evidence; however, prospective interventional and association studies were also included for completeness.

A comprehensive comparison of the eighty-seven studies included in the present review is provided in Table 1. When enough data were reported, the 95 % CI for the changes in plasma apoB and other lipoprotein parameters were calculated for the individual studies (Table 1). A table summarising the overall direction of changes in lipoprotein parameters based on the number of RCT supporting the findings is also provided (Table 2). Of note, the studies examined here that are summarised in Table 2 use data from the eighty-seven studies that examined plasma apoB in addition to other lipoprotein parameters to allow comparison between the parameters. Thus, the present review may not be comprehensive for the effect of the dietary components and patterns on plasma cholesterol, TAG and apoA1.

Table 1 Summary of nutritional interventions affecting plasma apoB and other lipoprotein-related parameters*

↓, Significant decrease in the plasma parameter examined; ↑, significant increase in the plasma parameter examined; –, no significant effect; AMR101, eicosapentaenoic acid ethyl ester; CHO, carbohydrates; CLA, conjugated linoleic acid; cross-sect., cross-sectional study; CRP, C-reactive protein; DASH, Dietary Approaches to Stop Hypertension; dyslipid, dyslipidaemic; FA, fatty acids; FCR, fractional catabolic rate; HbA1c, glycated Hb; HDL-C, HDL-cholesterol; HFCS, high-fructose corn syrup; hyperchol, hypercholesterolaemic; hyperlipid, hyperlipidaemic; LDL-C, LDL-cholesterol; M, men; MCFA, medium-chain fatty acids; Med, Mediterranean; NCEP ATP III, National Cholesterol Education Program Adult Treatment Panel III; N/E, not examined; non-HDL-C, non-HDL-cholesterol; normolipid, normolipidaemic; MS, metabolic syndrome; P-OM3, prescription omega-3-acid ethyl esters; Pros, prospective intervention study; RCT, randomised controlled trial; Ref, reference; RESMENA, Reduction of the Metabolic Syndrome in Navarra-Spain; RLP, remnant-like particles; ROH, alcohol; RT, resistance training; T2D, type 2 diabetes; TRL, TAG-rich lipoproteins; VAT, visceral adipose tissue; VLDL-C, VLDL-cholesterol; W, women.

a Significant effect v. baseline; b significant effect v. control, placebo or other test diets. For cross-sectional studies, the effects were based on differences in group means. When more than two diets were compared, each diet was labelled by a letter to indicate the diets compared.

* The Table summarises the effects of each dietary component or intervention presented in the horizontal subtitles on plasma concentrations of apoB and other lipoprotein-related parameters.

n Represents the number of subjects analysed in each study for plasma apoB, except when indicated as either enrolled or completed.

Percentage macronutrient represents percentage of total daily energy intake of each nutrient. Percentages of energy intake from macronutrients were estimated, when necessary, using Atwater coefficients (4 kcal/g for carbohydrates and protein, 9 kcal/g for lipids). To convert energy intake to kJ, multiply by 4·184.

§ When enough data were provided, the effect size was calculated as a 95 % CI based on the change during the intervention in comparison with control, placebo or other test diets.

Non-HDL-C refers to non-HDL-C, LDL-C and/or VLDL-C depending on the data provided in each paper. To convert cholesterol concentrations to mg/dl, multiply by 38·67.

To convert TAG concentrations to mg/dl, multiply by 88·57.

Table 2 Summary of the effects of dietary components and healthy dietary patterns on plasma apoB and lipoprotein parameters based on the original human studies examined in the present review

Non-HDL-C, non-HDL-cholesterol; HDL-C, HDL-cholesterol; ↓, majority of the studies reviewed (>50 %) reported a decrease; ↔, lack of effect, controversial findings (<50 % in agreement) or insufficient data (≤2 studies); CHO, carbohydrates; ↑, majority of the studies reviewed (>50 %) reported an increase; LDL-C, LDL-cholesterol; N/E, not examined; FA, fatty acids; DASH, Dietary Approaches to Stop Hypertension; VLDL-C, VLDL-cholesterol; RCT, randomised controlled trial.

* Non-HDL-C includes non-HDL-C, LDL-C and/or VLDL-C depending on the data provided.

Marks the dietary component or pattern with consistent effect based on >3 RCT.

Marks the dietary component or pattern with consistent effect based on 2–3 RCT.

§ Effects examined in subjects with the metabolic syndrome and/or dyslipidaemia only.

Includes conclusions reported in a previous meta-analysis.

Evidence derived from cross-sectional studies and association analysis.

Effect of hypoenergetic diet-induced weight loss on plasma apoB

Obesity promotes cardiometabolic disease, and weight loss as modest as 5–10 % has been reported to ameliorate the risks of T2D and CVD( 38 40 ). Hypoenergetic diet (about 5440–7110 kJ; 1300–1700 kcal)-induced weight loss of about 6–12 % was reported to decrease plasma apoB, whether on a low-fat/high-CHO diet (≤30 % fat; >45 % CHO)( 37 , 41 , 42 ), a higher-fat/moderate-CHO diet (>30 % fat; 26–45 % CHO)( 37 , 43 , 44 ) or when combined with resistance training (4 % weight loss)( 45 ). Similar effects were reported for a very-low-energy diet (2510–3350 kJ (600–800 kcal); 6 % weight loss)( 46 ). Reduction in plasma apoB is proposed to be due to the reduction in VLDL production rate and conversion to LDL and to the increase in LDL catabolic rate( 43 ), and appears to mirror that of TAG particularly in subjects with dyslipidaemia or the metabolic syndrome. Addition of ezetimibe (a cholesterol-lowering agent) to a hypoenergetic diet did not have an additional benefit on plasma TAG and VLDL-apoB100 concentrations and secretion rates( 41 ). Moreover, increasing the frequency of meals in RESMENA dietary pattern (seven v. five meals/d) did not induce a further decrease in plasma apoB( 44 ). (Note that The RESMENA-S study (Reduction of the Metabolic Syndrome in Navarra-Spain) is an RCT comparing two hypoenergetic diets with an energy deficit of 30 % of requirements; the RESMENA dietary pattern has a macronutrient distribution of 40/30/30 (CHO/fat/protein) and high meal frequency (seven meals/d), while the control diet is based on the American Heart Association guideline and has a macronutrient distribution of 55/30/15 and a lower meal frequency (three to five meals/d)( 41 ).)

Of note, the effect of changes in fat depots on plasma apoB may be sex-dependent. In a 1-year study using a hypoenergetic diet combined with aerobic training in 107 obese men with dyslipidaemia, reduction in plasma apoB was dependent on the reduction in visceral adipose tissue( 47 ). In a study by our group in fifty-six postmenopausal obese women, a 6-month hypoenergetic diet induced a reduction in plasma apoB that was independent of changes in adiposity or visceral adipose tissue but dependent on baseline apoB( 42 ), which in turn was negatively associated with the diet quality( 48 , 49 ).

Thus, in all four RCT and three prospective interventional studies examining 335 healthy or dyslipidaemic overweight and obese subjects in total, hypoenergetic diet-inducing weight loss (about 6–12 % alone or 4 % with resistance training) over 4–52 weeks induced a reduction in plasma apoB and TAG (six studies for TAG), with less consistent changes in non-HDL-C, LDL-C and HDL-C, and no data for VLDL-C( 41 47 ). When examined, there was no effect on plasma apoA1 (four studies) and a decrease in plasma apoB:apoA1 (two studies) (Table 2). More studies are needed to evaluate whether sex differences exist in the regulation of plasma apoB by changes in body fat distribution, and to confirm whether plasma apoB:apoA1 is decreased with weight loss in overweight and obese subjects.

Effects of macronutrients on plasma apoB


Current Canadian and American guidelines for the prevention of chronic diseases recommend a balanced diet with 45–65 % CHO, 20–35 % fat and 10–35 % protein( 50 52 ). However, high CHO/low-fat-diets are associated with higher plasma total, VLDL- and chylomicrons-TAG in the fasting and postprandial states( 14 , 53 ) and with higher apoB and Lp(a)( 54 56 ). For example, switching 140 healthy men from 4 weeks on a moderate CHO (45 %)/high-fat (40 %) diet to 4 weeks on a high CHO (65 %)/low-fat-diet (20 %) with equivalent 50:50 ratio of simple to complex CHO, increased plasma apoB, TAG, Lp(a) as well as apoC-III (an inhibitor of lipoprotein lipase, whose activity is vital to hydrolyse and clear plasma TAG)( 56 ) (Table 1). The effects of these diets on plasma apoB and TAG are believed to be primarily due to higher CHO flux to the liver increasing de novo lipogenesis and production of apoB-lipoproteins( 57 ). Moreover, elevated TAG promotes cholesteryl ester transfer protein activity (CETP)( 58 ), which favours the exchange of cholesterol on HDL and LDL particles with TAG on TAG-rich lipoproteins (TRL, namely VLDL and chylomicrons) and may explain lower plasma LDL-C and HDL-C with these diets( 54 56 ).

Compared with high-CHO diets (49–65 %), moderate-CHO (26–45 %)/high-fat diets (38–46 %) were reported to improve plasma apoB, TAG and HDL-C but produced less consistent effects on plasma LDL-C( 56 , 59 62 ) (Table 1). Notably, compared diets within each study( 56 , 59 62 ) contained equivalent amounts of fibre (about 25–30 g/d) or equivalent simple:complex CHO ratio (50:50), excluding the confounding effects of these nutrients (as discussed in the Simple sugars and Dietary fibres sections below). The benefit of the reduction in CHO content, especially in regards to plasma apoB, appears to be dependent on the type of nutrient used to replace CHO. When the types of FA were compared concomitantly in a large RCT on 178 healthy overweight and obese men and compared with a high-CHO diet (54 % CHO), a moderate-CHO diet (26 % CHO) reduced plasma apoB (95 % CI –0·05, –0·16 g/l adjusted for weight) only in combination with a higher MUFA content (27 % MUFA, 9 % SFA, which also induced weight loss) not a higher SFA content (20 % MUFA, 15 % SFA)( 59 ). In line in a smaller cross-over RCT on forty healthy men, the reduction in CHO intake alone (50 % to 31 %) without a change in the percentage of fat, MUFA and SFA content (38, 15 and 15 %, respectively) did not affect plasma apoB( 62 ). Plasma apoB was only reduced when MUFA content was increased to 21 % and that of SFA was decreased to 8 % in the same moderate-CHO diet (31 %)( 62 ). Even within a high-CHO diet, a decrease in CHO content (55 to 50 %), accompanied by an increase in MUFA content (11 to 17 %) and equivalent amount of fibre, was reported to decrease plasma apoB, VLDL-C, TAG and increase HDL-C in hypercholesterolaemic men( 63 ). Larger studies are needed to determine which nutritional component has the largest effect on plasma apoB: the reduction in CHO, the increase in MUFA, or the decrease in SFA intake.

Further restriction in CHO intake to less than 10 % in very-low-CHO diets does not appear to influence plasma apoB, particularly when with high SFA intake usually associated with these diets (about 20 %) despite additional benefits on plasma TAG and HDL-C( 64 , 65 ) (Table 1). This may explain why compared with the very-low-CHO Atkins diet (58 % fat; 30 % SFA), weight maintenance for 4 weeks on the very-high-CHO Ornish diet (9 % fat; 3 % SFA) decreased plasma apoB (95 % CI –0·03, –0·19 g/l)( 66 ). Notably, lowering SFA intake is also reported to increase flow-mediated vasodilatation (i.e. a measure of endothelial function)( 67 ), which may add to the benefits of low-SFA diets.

Thus, in all four RCT and two prospective interventional studies examined including 452 subjects in total, plasma apoB was consistently reduced in healthy or hyperlipidaemic subjects with isoenergetic diets composed of 26–50 % CHO, 36–46 % fat, 14–32 % protein, 11–27 % MUFA, 5–14 % PUFA and 7–13 % SFA consumed over 3–4 weeks only( 56 , 59 63 ). Plasma TAG and HDL-C were also improved, while inconsistent or insufficient data were observed for non-HDL-C, LDL-C, VLDL-C and apoA1. None of the studies evaluated plasma apoB:apoA1 (Table 2). The macronutrient composition of these six studies( 56 , 59 63 ) was used to generate the summary of the isoenergetic diets observed to reduce plasma apoB (reported in the Abstract and Conclusion).

Simple sugars

The American Heart Association recently issued a strict recommendation to limit the intake of added sugars to 630 and 420 kJ/d (150 and 100 kcal/d) for men and women, respectively (about 6–7 % of total energy)( 68 ). The Dietary Intake Reference for Canadians remains more permissive with a maximal intake of ≤25 % of total energy( 51 ). However, neither guideline distinguishes between the types of simple sugars. Compared with glucose, fructose intake is known to be a poor stimulant of insulin secretion due to the low expression of its receptor, GLUT5, in the pancreas( 69 ). A high-fructose diet decreases hepatic insulin sensitivity and raises de novo lipogenesis and plasma TAG, effects which hinder hepatic degradation of apoB and enhance VLDL secretion( 70 ).

Human research on the differential effects of fructose and glucose on plasma apoB is limited to two non-RCT studies (55 % CHO, 30 % fat and 15 % protein), small sample size (n 7–48) and short duration (2–10 weeks) (Table 1). Nevertheless, their results are consistent with present knowledge on the negative effects of fructose metabolism on plasma apoB and postprandial TAG( 69 , 71 ). In addition, increased fasting glucose and decreased postprandial insulin secretion were also reported in one study with fructose v. glucose intake( 69 ). Notably, however, both studies used 25 % of energy from fructose alone( 69 , 71 ), which may not represent usual intake. More RCT are needed to determine the effect of habitual fructose intake on plasma apoB, apoB:apoA1 and other lipoprotein-related parameters.

Dietary fibres

Epidemiological and clinical studies suggest that high intake of dietary fibre is associated with reduced risk of T2D and CVD( 72 ). Soluble fibres, such as psyllium, reduce the reabsorption of bile acids, thus increasing cholesterol excretion( 73 ). Moreover, in guinea-pigs, psyllium was reported to decrease the secretion of VLDL particles and their conversion to LDL, and to enhance VLDL and LDL apoB turnover by increasing hepatic LDL receptor expression( 74 ). Soluble fibre consumption up to 10–25 g/d is recommended for hypercholesterolaemic patients by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)( 75 ) as it consistently lowers LDL-C( 76 79 ). It has, however, little, if any, effect on plasma TAG and HDL-C( 76 79 ).

Human research examining the effect of dietary fibres on plasma apoB is limited to four RCT, the results of which are, however, promising (Table 1). One RCT reported that psyllium soluble fibre (7·68 g/d), in combination with plant sterols (2·6 g/d), decreased plasma apoB in subjects with hypercholesterolaemia( 76 ) due to reduction in intermediate-density lipoprotein and LDL numbers. Interestingly, there was also a reduction in small HDL particles possibly adding to the anti-atherogenic effects of this diet. Similarly, cocoa cream enriched with hazelnuts, phytosterols (2 g/d) and soluble fibre (20 g/d) reduced plasma apoB100 and LDL-C compared with a control cocoa cream in hypertensive and hypercholesterolaemic subjects( 78 ). Concordant results were drawn from another RCT where the addition of Metamucil (11 g/d psyllium soluble fibre) to simvastatin therapy (10 mg, cholesterol-lowering agent) had a similar hypocholesterolaemic effect as a higher dose of simvastatin (20 mg)( 77 ). Soluble fibres also include α-cyclodextrin, which is derived from maize and is known to form a complex with dietary fat, reducing its bioavailability. In contrast to psyllium, no effect of α-cyclodextrin intake was observed on plasma apoB in one RCT on healthy subjects despite lower plasma LDL-C( 79 ).

Thus, in all three out of four RCT conducted on dyslipidaemic subjects (n 214 in total) and ranging from 4 to 8 weeks, the intake of soluble fibre (about 8–20 g psyllium) on a dietary background of 44–50 % CHO, 36–41 % fat and 15–17 % protein reduced plasma apoB and LDL-C but did not affect TAG( 76 79 ). Less consistent or no data exist for VLDL-C, HDL-C, apoA1 and apoB:apoA1 (note that the macronutrient composition of these diets fits within the range reported to reduce plasma apoB in the Abstract and Conclusion). More RCT are needed to examine the independent effects of the quantity and/or types of soluble fibres on plasma apoB and apoB:apoA1.



High intake of SFA is known to increase plasma total, LDL-C and HDL-C and to be associated with a higher risk of cardiometabolic disease compared with the intake of unsaturated fats( 54 ). Current FAO/WHO guidelines limit SFA intake to less than 10 % of total energy, with the remaining fat sources as PUFA (6–11 %) or MUFA( 80 ). Notably, the higher limit of PUFA at <11 % was set as the risk for lipid peroxidation may increase with higher intake, particularly when tocopherol (vitamin E) intake is low( 80 ).

A meta-analysis on twenty-five RCT( 81 ) together with four more recent RCT and a controlled parallel trial confirmed that decreasing SFA intake by increasing MUFA intake lowers plasma apoB and LDL-C, but are less consistent in regards to plasma TAG, HDL-C, apoA1 and apoB:apoA1( 62 , 82 86 ) (Table 1). In the largest RCT on 548 individuals at high risk of the metabolic syndrome, 24 weeks on a high-MUFA diet (16 %) decreased plasma apoB compared with an isoenergetic diet with high-SFA (16 %) on a similar moderate-CHO (about 42–45 %) and -fat (36–38 %) backgrounds( 82 ). Of note, however, an even greater effect of a combination of low fat (26–28 %) and low SFA (8–9 %) was observed on plasma apoB in that study that counterbalanced the effect of higher CHO (about 51–52 %), suggesting that lowering SFA intake is key( 82 ). Similar effects were also observed in eighty-five dyslipidaemic subjects at risk for T2D within high-CHO diets, where a high-CHO (55 %)/low-fat (29 %)/low-SFA (8 %) diet did not increase plasma apoB when compared with a lower-CHO (49 %)/high-fat (36 %)/high-SFA (16 %) diet with similar MUFA (16 and 14 %) and PUFA (6 %) backgrounds( 83 ), underlying the effects of low SFA. This further underscores the need for head-to-head comparison between the specific effects of CHO, SFA and MUFA on plasma apoB. The beneficial effects of replacing SFA by MUFA were also observed in healthy men following a moderate-CHO diet (31 %)( 62 ), in healthy subjects following a high-CHO diet (48 %)( 84 ), in subjects at risk for T2D following a high-CHO diet (49 %)( 83 ), and in healthy abdominally obese subjects following moderate- to high-CHO diets (41 and 46 % CHO; 95 % CI –0·09, –0·21 and –0·03, –0·17 g apoB/l, respectively)( 85 , 86 ). Finally, in the same meta-analysis by Mozaffarian & Clarke( 81 ) on twenty-five RCT, while isoenergetic replacement of SFA by PUFA reduced plasma apoB, LDL-C and HDL-C, and induced a greater reduction in LDL-C than MUFA, the two types of unsaturated FA had similar effects on plasma apoB. This is also in line with another RCT on hypercholesterolaemic subjects( 87 ). No additional studies were found on the effect on PUFA on plasma apoB except for those examined in the section on n-3 PUFA.

A recent review on lipoprotein kinetics in humans suggests that the intake of SFA increases the pool size of LDL-apoB100 particles by decreasing their fractional catabolic rate( 30 ). SFA may also be linked to cardiometabolic risk through the activation of inflammatory cascades via Toll-like receptors 2 and 4 and the NF-κB-dependent pathway in murine and human cells, as reviewed( 88 ). This is believed to promote systemic inflammation and insulin resistance, both of which are known to reduce insulin-mediated degradation of apoB by the liver and TRL clearance by adipose tissue( 70 , 89 ). SFA can also amplify lipopolysaccharide response by promoting the generation of ceramides that activate protein kinase C–ζ and mitogen-activated protein kinases in monocytes( 90 , 91 ). Reducing SFA intake is associated with an increase in the expression of LDL receptors on mononuclear cells in humans, promoting LDL uptake( 89 , 92 ). It should be noted, however, that the association of SFA intake with chronic inflammation in humans remains controversial and may be dependent on the inflammatory marker examined( 93 , 94 ). A recent systemic analysis reported that, while positive associations were found between SFA intake with soluble intercellular adhesion molecule-1 and IL-6, no significant association or insufficient data were found with other markers such as E-selectin, TNFα and C-reactive protein( 93 ).

In summary, in four RCT and one controlled parallel trial examined in the present review including 737 healthy or dyslipidaemic subjects, a consistent beneficial effect of reducing SFA intake (from 19 % to 8 %) by increasing MUFA intake (from 10 % to 21 %) was observed on plasma apoB and LDL-C using diets composed of 31–51 % CHO, 26–40 % fat and 11–32 % protein( 62 , 82 86 ). These findings support an earlier meta-analysis published to date( 81 ). Plasma HDL-C was reduced with these diets, probably a reflection of the reduction in plasma cholesterol, while less consistent or insufficient data exist for VLDL-C, TAG, apoA1 and apoB:apoA1 in these studies( 62 , 82 86 ). Of note, in addition to the six diets in the section on CHO (Carbohydrates section), the macronutrient composition of the five studies examined here were used to generate the summary of the isoenergetic diets observed to reduce plasma apoB (reported in the Abstract and Conclusion).

Marine- and plant-derived n-3 PUFA

Fish oil and n-3 FA found in fish oil, EPA and DHA, have been reported to improve dyslipidaemia, inflammation, insulin resistance and hepatic steatosis in mice and humans( 95 , 96 ). The American Heart Association recommends fish consumption, at least two servings per week, or fish oil supplementation to reduce the risk of CVD( 97 ). Similarly, the Canadian Cardiovascular Society Guidelines indicates that the intake of n-3 FA (2–4 g/d of both EPA and DHA), under a physician’s care, can lower plasma TAG by 25–30 % in patients with hypertriacylglycerolaemia( 1 ). Increasing n-3 FA intake decreases plasma TAG and frequently VLDL-C, but rarely affects LDL-C and HDL-C( 98 104 ).

Reduction in plasma apoB and TAG has been reported by all four RCT and one parallel trial reviewed using marine-derived n-3 FA supplementation (3·2 and 3·4 g/d of EPA:DHA at a 1·2:1 ratio( 99 , 103 , 104 ) or 4 g/d EPA alone( 98 )) or high fish intake (1·1–1·7 g n-3 FA/d)( 101 , 105 ), for 6–24 weeks in hyperlipidaemic subjects not taking hypolipidaemic agents (Table 1). Less consistent effects have been reported for LDL-C, VLDL-C, non-HDL-C and HDL-C and insufficient data exist for apoA1 or apoB:apoA1 in these studies. When added to statins (i.e. cholesterol-lowering agents), P-OM3 (prescription omega-3-acid ethyl esters; 3·4 g/d; EPA:DHA at a 1·2:1 ratio) further decreased plasma apoB in hyperlipidaemic patients, when simvastatin (40 mg; n 254)( 99 ) not atorvastatin (10–40 mg/d; n 219)( 100 ) was used. However, it is reported that atorvastatin induces a greater reduction in plasma apoB than simvastatin( 106 , 107 ), which may limit additional benefits of the n-3 FA. Using a cross-over design, modulating the ratio of n-6:n-3 in a diet supplemented with 2·2 g/d marine-derived n-3 FA had no effect on plasma apoB in eleven hypercholesterolaemic subjects on statin treatment( 102 ).

Kinetics studies have demonstrated that the reduction in plasma TAG and apoB by n-3 FA in human subjects is mainly due to the reduction in the production rate of apoB100 and apoB48 TRL( 103 105 ), as recently reviewed( 30 32 ). When combined with weight loss, n-3 FA induce a greater reduction in fasting apoB48 production rate and postprandial apoB48 concentrations( 104 ). As secretion of TRL-TAG and TRL-apoB are closely linked, decreased TRL apoB100 secretion may be due to the inhibition of enzymes involved in TAG synthesis such as diacylglycerol acyltransferase and FA synthase, suppression of sterol regulatory element binding protein-1c gene transcription, and activation of β-oxidation( 105 , 108 ). In addition, both n-3 FA and n-6 PUFA favour hepatic apoB degradation in the post-endoplasmic reticulum pre-secretory proteolysis pathway through reactive oxygen species-induced autophagy( 109 ).

Observational studies also support that higher intakes of plant-derived n-3 FA (α-linolenic acid), but not plasma levels( 110 ), are significantly associated with moderately lower risk of CVD( 97 , 110 ). The use of vegetable oils is encouraged to increase the intake of α-linolenic acid up to 0·6–1·2 % of total energy, the acceptable macronutrient distribution range established by the Institute of Medicine( 111 ). While few studies have examined the effect of plant-derived n-3 FA on apoB, a recent RCT on 179 healthy postmenopausal women reported that the intake of 40 g/d of flaxseeds with high α-linolenic acid compared with an equal amount of wheat germ had a small but modest benefit on plasma apoB (95 % CI –0·00, –0·09 g/l; Table 1)( 112 , 113 ). However, the conversion of plant- into marine-derived n-3 FA is at less than 1 %( 114 ) and the mechanism by which α-linolenic acid benefits cardiometabolic health in humans may not involve plasma lipids and apoB.

In summary, for all four RCT and one parallel study conducted mostly on hyperlipidaemic subjects (n 411 in total) and ranging from 6 to 24 weeks, the intake of marine-derived n-3 FA, from oily fish (1·1–1·7 g/d) or supplementation (3·2–3·4 g/d EPA and DHA or 4 g/d EPA alone) reduced plasma apoB and TAG with less consistent benefits or insufficient data on the other lipids( 98 , 101 , 103 105 ). Insufficient data also exist for the additional benefit of n-3 FA in combination with statins (two RCT; n 473) (note that not all studies reported the macronutrient or FA composition of the background diets to provide their summary). More RCT examining the additional effects of n-3 FA in combination with hypolipidaemic agents on plasma apoB and the apoB:apoA1 ratio are needed.

Trans-fatty acids

A higher consumption of trans-FA from industrial partially hydrogenated fats, a characteristic of the Western diet with high intake of processed food, is associated with higher risk of CVD( 31 ). Isoenergetic substitution of trans-FA by SFA reduces plasma apoB and apoB:apoA1 and increases HDL-C and apoA1, as reported in a meta-analysis of thirteen trials( 81 ). Only two more recent RCT were found, in both of which decreasing trans-FA (from 7·5 and 4·3 % to <0·5 %) by increasing cis-PUFA( 115 ) or cis-MUFA( 116 ) also led to a decrease in plasma apoB. Trans-FA increase the pool size of LDL apoB100 by decreasing their fractional catabolic rate, but have no effect on VLDL apoB100( 30 ).

Trans-FA can also be produced naturally during the biohydrogenation of dietary PUFA by anaerobic bacteria in the rumen, and thus exist in small amounts (about 2–5 %) in meat and dairy products derived from ruminants( 117 ). Contradictory findings exist regarding the impact of natural trans-FA on CVD risk; while observational studies found no association( 118 ), a cross-over trial reported that a diet high in conjugated linoleic acids and naturally occurring double-bonds increased plasma apoB and LDL-C and decreased HDL-C compared with a high-MUFA diet( 116 ). Contradictory findings also exist as to whether industrial trans-FA have a higher( 116 ) or a lower( 119 ) impact on plasma apoB than natural trans-FA. However, sex-specific effects of natural trans-FA on increasing plasma LDL-C, HDL-C, apoB and apoA1 in women but not in men have been reported and may need to be accounted for in future studies( 119 ).

Of importance to note is that, in 2007, Health Canada recommended that the content of trans-FA in vegetable oils and soft, spreadable margarines should be limited to 2 % of the total fat, while that of all other foods including ingredients sold to restaurants should be limited to 5 %. It also gave the food industry a 2-year window to achieve these recommendations( 120 ). This strategy appears to have achieved a positive impact, as the Canadian consumption of trans-FA has declined by 40 % over the past decade (from 8·4 to 4·9 g/d)( 120 ). Moreover, in June 2015, the US Food and Drug Administration removed partially hydrogenated oils, the main source of artificial trans-FA in processed foods, from the ‘generally recognized as safe’ list and gave food manufacturers 3 years to remove them from their products( 121 ). The current recommendation to promote cardiovascular health by both the American( 52 ) and the Canadian( 51 ) guidelines is to reduce trans-FA to the least possible. This is also in line with the recommendation of the WHO of <1 % of total energy per d( 120 ). Thus, while plasma apoB was increased in the two RCT examined, the amounts of trans-FA used (4·3 % or about 11 g/d( 115 ) and 7·5 % or about 20 g/d( 116 )) are unlikely to represent current habitual intake.

Medium-chain fatty acids

Medium-chain FA (MCFA) contain 6–12 carbons. Unlike long-chain FA, MCFA are usually absorbed directly into the portal circulation without the need for being incorporated in the chylomicron particles. Accordingly, oil made from MCFA is prescribed to treat patients with familial hyperchylomicronaemia( 122 ).

Only two studies with limited sample size (n 28 and 51) and duration (4 and 12 weeks) were reported on the effect of MCFA on plasma apoB in human subjects. Nevertheless, both studies reported no effect of high MCFA intake, as pure oil (20 g/d) or milk fat (8·5 v. 6·9 g/d), on fasting or postprandial plasma apoB, TAG, LDL-C, VLDL-C or apoA1( 123 , 124 ) in subjects with abdominal obesity alone( 124 ) or with secondary hypertriacylglycerolaemia( 123 ). No data were reported on plasma apoB:apoA1 in either study. These findings are also in line with the lack of an effect of MCFA on apoB reported in a recent review on the effect of dietary FA on lipoprotein metabolism( 30 ). As MCFA are suggested to increase fat oxidation( 125 ), more RCT comparing different types and higher doses of MCFA (with attention to possible gastrointestinal symptoms) or in combination with weight-loss intervention may be needed.

Dietary cholesterol

The impact of dietary cholesterol on plasma lipids and CVD risk remains controversial. To reduce the risk of CVD, the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) recommends limiting the intake of dietary cholesterol to 200 mg/d for subjects with hyperlipidaemia( 75 ). However, the recent American Heart Association/American College of Cardiology guidelines to reduce CVD concluded that there is insufficient evidence to determine whether lowering cholesterol intake reduces LDL-C( 126 ). Studies examining the specific effect of cholesterol on plasma apoB are also scarce and limited in size( 127 , 128 ). Consumption of a high-cholesterol diet (804 mg/d; three eggs/d) in twenty-five normolipidaemic healthy young men increased plasma LDL-C, HDL-C and apoB, without affecting plasma TAG, apoA1 and Lp(a) compared with a low-cholesterol diet( 127 ). In contrast in patients with T2D or prediabetes (42 % on lipid-lowering medications), consumption of a high- or low-cholesterol (590 v. 228 mg/d)/hypoenergetic/high-protein diet led to similar reductions in weight and plasma apoB, non-HDL-C, TAG, glucose, and insulin and blood pressure, whereas only the high-cholesterol diet led to an increase in HDL-C( 128 ). However, weight loss and improved insulin sensitivity on both diets may have masked the effects of high cholesterol per se on plasma apoB. More RCT are needed to determine the independent effect of dietary cholesterol on plasma apoB and apoB:apoA1.


Phytosterols are plant-derived steroid compounds similar in structure and function to cholesterol( 129 ). Current recommendations for hyperlipidaemic patients( 75 ) include 2 g/d of phytosterols, which is known to reduce LDL-C( 130 , 131 ). Dietary sources of phytosterols include vegetable oils, cereals and nuts and provide about 300 mg/d, as reported in a British population( 132 ). Only three RCT explored the effects of phytosterol-enriched foods in subjects with the metabolic syndrome( 133 ), hypertension and/or hypercholesterolaemia (n 254 in total)( 76 , 78 ). All three RCT reported a consistent improvement in plasma apoB and LDL-C when phytosterols were added to a yogurt drink (4 g/d)( 133 ), a cocoa–hazelnut cream (2 g/d)( 78 ) or in combination with soluble fibres (7·68 g/d psyllium and 2·6 g/d phytosterols( 76 )). It is thus not possible to isolate an independent effect of phytosterol alone in these RCT. Of note, the background dietary composition of the phytosterol-enriched diets was 37–50 % CHO, 36–44 % fat and 15–17 % proteins, which is within the range observed to reduce plasma apoB (reported in the Abstract and Conclusion). More studies are needed to confirm the effect of phytosterols per se on plasma apoB and other lipids.


Soya proteins

Following the publication of a meta-analysis supporting the negative association of soya protein intake with plasma cholesterol( 134 ), the US Food and Drug Administration permitted the food industry to claim that ‘25 grams of soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease’( 135 ). Soya proteins are reported to increase the clearance of apoB-lipoproteins by enhancing the synthesis of bile acid, increasing LDL receptor activity, and reducing hepatic particle secretion( 136 , 137 ). On the other hand, increased insulin growth factor binding protein-3 has also been reported with soya protein intake, which suggests reduced bioavailability of insulin growth factor-1 and increased CVD risk( 138 ).

Eight RCT explored the impact of isolated soya proteins, in comparison with isolated milk proteins, on plasma apoB and lipids and their findings are inconsistent. Replacement of isolated milk proteins by isolated soya proteins (25–30 g/d) reduced plasma apoB, LDL-C and non-HDL-C in hypercholesterolaemic or hyperlipidaemic patients without( 139 ) or with haemodialysis( 140 , 141 ), but had no effect on plasma LDL-C or apoB in normolipidaemic subjects( 140 ). However, accumulation of isoflavones due to lack of renal excretion and unavailability of isoflavones for dialysis have been reported, which may limit the applicability of the results( 142 ). In contrast, no benefits on plasma apoB were reported in healthy men( 143 145 ) or patients with diet-controlled T2D( 146 ) consuming isolated soya proteins in comparison with isolated milk proteins, nor in healthy subjects supplemented with black soya peptide in comparison with casein( 147 ). On the other hand, an RCT in hypercholesterolaemic postmenopausal women reported an increase in plasma apoB, which was, however, accompanied by an increase in weight with both soya and casein proteins( 138 ).

It should be noted, however, that an interaction was identified between plasma apoB and equol urinary excretion status( 146 ). Equol is a type of isoflavone produced endogenously in the intestine, which not all humans have the ability to synthesise( 148 , 149 ). It has a greater oestrogen receptor-binding affinity and antioxidant capacity than other types of isoflavones. This may add to the inter-subject variability in the response to isoflavones. Moreover, as isoflavones are known to bind oestrogen receptors( 150 ), sex differences may also need to be explored. In addition to isoflavones, soya protein isolates contain other components such as saponins, phytic acid and trypsin inhibitors, which are biologically active molecules that may influence lipid profile( 136 ). While the specific effect of isoflavones on plasma apoB and lipids is yet to be demonstrated( 143 145 ), that of the other components have not yet been examined.

Finally, the effect of non-soya protein was also examined in one RCT in comparison with casein protein in thirty-eight hypercholesterolaemic subjects. The intake of 25 g/d of cowpea protein isolate was reported to decrease plasma apoB, non-HDL-C and LDL-C and to increase plasma HDL-C( 151 ).

In summary, inconsistent findings were observed in eight RCT (n 341; 4–52 weeks) examining the effect of replacing isolated milk proteins or casein with soya proteins on plasma apoB and lipids( 138 147 ). However, three out of the four RCT conducted with 121 hyperlipidaemic subjects reported a decrease in plasma apoB and LDL-C with the intake of 25–30 g/d isolated soya protein over 4–12 weeks. More RCT are needed to confirm whether the effects of soya proteins are specific to subjects with hyperlipidaemia, are restricted to a specific soya protein component (i.e. isoflavones) or include other non-soya legume proteins.

Whey proteins

Milk proteins comprise a soluble fraction named whey and an insoluble fraction named casein( 152 ). Whey proteins are recognised as immunomodulators, antioxidants and nutrient carriers (FA, retinol and Fe). Studies on the effect of whey proteins on lipid metabolism are scarce. However, consumption of 60 g/d whey protein, compared with an equal amount of casein, on a similar background diet of milk fat (63 g/d) with low or high MCFA reduced postprandial apoB48 in fifty-one subjects with abdominal obesity, an effect that remained significant after adjustment for age, sex, blood pressure, statin intake and weight change( 124 ). More RCT are needed to explore the effect of whey protein v. casein or other types of proteins on lipoprotein profile in healthy and hyperlipidaemic subjects.


The Canadian Low-Risk Alcohol Drinking Guidelines recommend moderate alcohol consumption, defined as less than fifteen drinks for men and ten drinks for women per week( 153 ). The protective effect of alcohol consumption, ranging from low to high, on plasma HDL-C was reported in the Atherosclerosis Risk in Communities (ARIC) cross-sectional study in 8932 middle-aged subjects( 154 ). In contrast, only low-to-moderate alcohol consumption (about 1·5 drinks/d), compared with lack of, was associated with a lower plasma apoB and TAG in that study, and the effect was limited to wine drinkers who were also white women( 154 ). In another cross-sectional study in 2907 Swedish adults, total ethanol intake (about one drink/d) correlated with lower plasma apoB in women only and higher HDL in all subjects after adjustment for multiple confounders( 155 ). In the larger Third National Health and Nutrition Examination Survey (NHANES III) study on 8708 adults, plasma apoB decreased across the quartiles of higher alcohol consumption (>2 and 1–2 drinks/d), although no adjustment was made for potential confounders such as the types of alcohol or sex( 156 ). In contrast, in a smaller cross-sectional study on 636 postmenopausal women, alcohol consumption was not associated with plasma apoB per se but with a lower plasma apoB:apoA1 ratio( 157 ).

Heavy alcohol consumption promotes alcoholic fatty liver disease, elevated hepatic apoB mRNA and higher plasma TAG( 158 , 159 ). This may explain why in the ARIC study, heavy alcohol consumption (>210 g/week or about >3 glasses/d for men, >105 g/week or about >1·5 glasses/d for women) did not have beneficial association with plasma apoB( 154 ). Moreover, a J-shaped relationship has been described in regards to plasma TAG, where low-moderate alcohol consumption is associated with lower plasma TAG while heavy alcohol consumption is associated with higher plasma TAG( 159 ). A similar relationship may exist in regards to plasma apoB.

Only two studies employed an RCT design to examine the effect of alcohol or grape extract on plasma apoB. In one RCT, daily consumption of red wine (about three glasses), though not dealcoholised red wine, reduced fasting plasma LDL-C and increased HDL-C, but had no effect on plasma apoB in forty-five postmenopausal women( 160 ). This is in contrast to in vitro findings where incubation of HepG2 cells( 161 ) or Caco-2 intestinal cells( 162 ) with either red wine or dealcoholised red wine, but not ethanol, reduced apoB100 synthesis and apoB48 secretions, respectively. Of note, red wine may provide a greater health benefit compared with other alcoholic beverages due to its high resveratrol content, a polyphenol recognised for its cardioprotective properties. In another RCT, resveratrol-enriched (8 mg) grape extract reduced plasma apoB and oxidised LDL without any effect on plasma TAG or HDL-C in statin-treated patients( 163 ). Finally, the few studies that examined the effect of alcohol on apoA1 (four studies) and apoB:apoA1 (two studies) reported a benefit on these parameters.

Thus, most evidence to date on the association of alcohol consumption with reduced plasma apoB is derived from three out of four cross-sectional population studies (20 547 in total( 154 157 )), while the available RCT on forty-five women reported no effect( 160 ). More research employing the RCT design is needed to explore the role of the quantity and the type of alcohol consumed on the regulation of plasma apoB, apoB:apoA1 and other lipoprotein-related parameters in healthy and hyperlipidaemic subjects.

Effects of micronutrients on plasma apoB

In line with their antioxidant properties that combat oxidative stress involved in the pathogenesis of T2D, high dietary intake of vitamins A, C and E and Mg have been associated with lower risk of diabetes( 164 , 165 ). Moreover, a protective role for a higher intake of vitamin D on the development of the metabolic syndrome has been reported in association studies( 166 , 167 ). However, interventional studies using these micronutrients reported conflicting results( 164 , 168 ) and none addressed plasma apoB. Much more research is needed in this area.

Effects of specific foods and healthy dietary patterns on plasma apoB

Studying the effect of healthy food items and dietary patterns is essential and may have a greater benefit on atherogenic apoB-lipoproteins than the individual components described above. This is due to their high complexity, possible nutrient interactions and presence of other non-nutritive bioactive components such as phytochemicals. Moreover, the effects of nutrients that may remain unidentified are also considered.

Specific foods

Nuts contain a high amount of fat of favourable FA composition, which would be expected to reduce plasma apoB. These food items are low in SFA and have almost half of their total fat content in the form of MUFA, except for walnuts that are predominantly composed of PUFA( 169 ). Nuts are also rich in fibre, several vitamins and minerals and phytochemicals including phenols (particularly walnuts), phytosterols, proanthocyanidins and carotenoids( 170 ). High intake of such phytochemical-rich foods has been associated with lower risk for abdominal obesity and hypertriacylglycerolaemia( 171 ).

Three RCT reported that the consumption of mixed nuts (75 g/d or half a portion in 117 T2D subjects)( 172 ), walnuts (43 g/d in forty healthy subjects)( 173 ) or hazelnuts (30 g/d in forty-six hypercholesterolaemic subjects)( 174 ) reduces plasma apoB, with no effect on TAG and inconsistent effects on the other lipoprotein parameters. In contrast, one RCT reported no effect of hazelnuts (30 g/d) when added to a cocoa cream alone, and a decrease in plasma apoB100 and LDL-C when combined with phytosterols and soluble fibre( 78 ). Of note, these studies used a background diet of 39–45 % CHO, 34–41 % fat, 15–19 % protein, 11–22 % MUFA, 9–12 % SFA and 5–14 % PUFA, which is within the ranges observed to reduce plasma apoB (summarised in the Abstract and Conclusion). More RCT are needed to confirm the effect of nuts on plasma apoB and other lipoprotein parameters.

Higher consumption of soya nuts and products is believed to favour a lower incidence of CVD in the Asian compared with the Western population( 175 177 ). However, results are inconsistent in regards to the effects of different soya products on plasma apoB. Consumption of soya nuts instead of equal amounts of non-soya products was reported to reduce plasma apoB and LDL-C in hypertensive, though not normotensive, postmenopausal women( 178 ). In contrast, no improvement in plasma apoB was reported in subjects on peritoneal dialysis with the consumption of soya flour that provided more soya proteins and fibres compared with a control meat diet( 179 ). On the other hand, fermented soyabean reduced plasma apoB, though not lipids, in healthy subjects( 180 ); however, fermentation of isoflavones is known to increase their bioavailability by carrying out their conversion from glycones to bioactive aglycones( 181 ).

Studies examining the effects of whole-grain- and legume-rich diets on plasma apoB are scarce and inconsistent. In one RCT in forty-six healthy women, a diet rich in whole-grain barley and legumes reduced plasma apoB and LDL-C in comparison with a diet with equivalent macronutrients and fibres( 182 ). In another study, no effects of mixed whole-grain cereal products on plasma apoB were reported in fifty-four subjects with the metabolic syndrome( 183 ). However, these specific foods contain prebiotics such as dietary fibre, resistant starch, α-galactosides and β-glucans, as well as polyphenols and phenolic acids, all of which can be used as substrates for colonic fermentation. The subsequent production of SCFA and their influence on lipid metabolism deserve further studies.

Other specific food items explored in regards to their effects on plasma apoB include: partially skimmed 2 % fat milk (3·2 servings/d) in twenty-seven postmenopausal women with abdominal obesity( 184 ), buttermilk (45 g/d) in thirty-four subjects with low risk of CVD( 185 ), kiwifruit (two per d) in seventy men with hypercholesterolaemia( 186 ), raw tomato (200 g/d) in thirty-two men with T2D( 187 ), and garlic powder (2·4 g/d allicin) in fifty-six subjects with severe coronary artery disease( 188 ). None of these foods had an effect on plasma apoB, and had only a minor, if any, effect on the other plasma lipoprotein parameters.

Mediterranean diet

The Mediterranean diet (Med diet) captured the interest of many scientists in the early 1960s because of longer life expectancy and lower prevalence of CVD observed in Greece and southern Italy( 189 ). These populations have a high consumption of fruits, vegetables, cereal products, potatoes, beans, nuts and seeds, use olive oil as the principal source of fat, have frequent intake of fish and sea products, moderate intake of wine, dairy products, poultry and eggs, and low intake of red meat and sweets. This dietary pattern translates into a diet that is moderate in alcohol, CHO and fat content, low in SFA and cholesterol, and high in MUFA, n-3 PUFA and fibre, all of which promote a lower plasma apoB. In addition to its high nutritional quality, a Med diet may reduce plasma apoB as it supports weight loss secondary to its low energy density and high satiety effect.

Of the seven studies examining the effect of a Med diet on plasma apoB, only two employed an RCT design. They reported a decrease in fasting plasma apoB (95 % CI –0·001, –0·056 g/l( 190 )) or postprandial apoB48( 191 , 192 ) on 13 weeks of a Med diet (45–46 % CHO, 35 % fat, and 18–20 % protein, 9–10 % SFA, 16–17 % MUFA, 6 % PUFA) in a total of 686 subjects at risk for CVD. A reduction in plasma TAG was also induced with both diets, while insufficient data exist for the other lipoprotein parameters. Notably, the high-MUFA/low-SFA content of the Med diet appears to play a major role. In a controlled parallel trial, a Western-type diet (46 % CHO, 40 % fat, 11 % protein) also reduced plasma apoB, LDL-C and TAG when MUFA intake was increased (11 to 20 %) and that of SFA was reduced (19 to 11 %) in abdominally obese subjects, and to a similar extent as a Med diet (average –0·10 v. –0·15 g/l, respectively)( 85 , 86 ). Results from two prospective intervention studies also support a favourable impact on plasma apoB and LDL-C, independent of weight loss( 193 195 ), which was attributed to increased LDL-apoB fractional catabolic rate( 194 , 195 ). Similarly, a large cross-sectional study (n 20 986) reported an association between a Med diet score and lower apoB:apoA1 and TAG and higher HDL-C, even after adjustment for BMI and nine other confounders( 196 ). The impact of a hypoenergetic Med diet as a weight-loss intervention is less clear; prospective intervention studies found either a reduction of( 194 , 195 ), or no impact on( 197 ), plasma apoB. However, the first population was in nineteen men with the metabolic syndrome( 194 , 195 ), while the other was in twenty-six healthy women( 197 ). Thus the heterogeneity and small sample size of the populations examined probably affected the outcomes.

In summary, two RCT and three intervention studies reported the reduction in plasma apoB, LDL-C and TAG using a Med dietary pattern (41–50 % CHO, 32–40 % fat, 15–20 % protein, 16–21 % MUFA, 7–11 % SFA, 5–7 % PUFA) over 4–13 weeks in a total of 823 subjects, the majority of whom (>94 %) were at risk for CVD( 85 , 86 , 190 195 ). Of note, the composition of these Med diets used fits within the macronutrient ranges observed to reduce plasma apoB (summarised in the Abstract and Conclusion). Furthermore, a large cross-sectional study also reported that higher adherence to a Med diet is associated with lower plasma apoB:apoA1 and TAG and higher HDL-C in 20 986 British subjects. More RCT are needed to confirm the beneficial effect of a weight-maintenance or a hypoenergetic Med diet on plasma apoB, apoB:apoA1 in comparison with other lipoprotein parameters in healthy and hyperlipidaemic subjects.

Vegetarian diet

Vegetarian diets are associated with lower plasma cholesterol and prevalence of CVD and T2D( 198 ). Vegetarian diets exclude meat, poultry and/or fish, while vegan diets exclude all animal products, resulting in lower SFA and cholesterol and higher MUFA, PUFA and fibre intake, which is expected to reduce plasma apoB. While this hypothesis is yet to be proven by RCT, three cross-sectional studies on vegetarian/vegan diets reported lower plasma apoB in Europeans (n 1694)( 199 ) and Buddhist monks (men) (n 296)( 198 ), even after adjustment for confounders such as BMI, while adjustment for BMI in sixty-two women eliminates their significance( 200 ). Vegetarian diets were also associated with lower HDL-C and apoA1 after adjustment for many confounders, probably secondary to their higher CHO content compared with the omnivorous control diets in these studies( 198 , 199 ). They were also associated with lower apoB:apoA1 in men( 200 ), while their association with lower apoB:apoA1 in women was eliminated after adjustment for BMI( 200 ). These findings need to be confirmed by RCT.

Moreover, indole-3-carbinol, which is produced from the breakdown of the glucosinolate glucobrassicin found at relatively high levels in cruciferous vegetables such as broccoli, cabbage, and cauliflower was reported to reduce apoB production in HepG2 cells( 201 ). Human studies are lacking and the role of the vegetarian diet and its components needs to be explored.

Nordic diet

Consumption of traditional Nordic foods has been associated with lower total mortality( 202 ). Though limited, two recent RCT using Nordic diets that mainly included higher intake of whole-grain products, berries, fruits, vegetables, rapeseed oil, fish and low-fat dairy products, and lower intake of sugar-sweetened products, reported a reduction in either plasma apoB (95 % CI –0·19, –0·31 g/l)( 203 ) or apoB:apoA1 ratio (95 % CI –0·01, –0·11 g/l)( 203 , 204 ) in subjects with hypercholesterolaemia or the metabolic syndrome. A less consistent effect was observed for LDL-C, HDL-C and apoA1, while no effect was reported for plasma TAG. The beneficial effects of Nordic diets may be attributed to higher intakes of fibre and PUFA and a lower intake of SFA( 203 , 204 ). Other dietary benefits include increased micronutrient intake (β-carotene, vitamin C, vitamin E, K, Mg) and/or decreased cholesterol and Na intake; although the specific effects of these nutrients on plasma apoB remain unclear. More RCT are needed to explore the effects of a Nordic diet on weight loss or maintenance in various populations.

Dietary Approaches to Stop Hypertension diet

The Dietary Approaches to Stop Hypertension (DASH) encourage higher intake of fruit and vegetables, whole-grain cereals, low-fat dairy products and nuts, and lower intake of salt, refined CHO and SFA. Two trials, one of which was a RCT, reported that a DASH diet led to a reduction in plasma apoB with variable effects on plasma lipids( 45 , 205 ). However, the impact of reduced Na intake per se on plasma apoB is rarely explored. One study that examined this reported no effect of a 7 d low-Na diet on plasma apoB, LDL-C and TAG with a decrease in HDL-C in normotensive men( 206 ). More RCT are also needed exploring the effects of a DASH diet on plasma apoB.

Palaeolithic diet

During the Palaeolithic period, our ancestors lived as hunter–gatherers, eating wild animal-source foods (lean meats, fish, eggs, no dairy) and uncultivated plant-source foods (fruits, vegetables, nuts, no cereal grains and legumes)( 207 ). This period was followed by agriculture (predominantly of cereals) and animal domestication and more recently, by the industrial revolution (refined fats and sugar, added salt), which introduced major dietary changes. One hypothesis states that time was insufficient for evolutionary adaptation and that a Palaeolithic diet would optimise our metabolism and reduce risk of contemporary chronic diseases. The only study that examined this hypothesis only included ten women with a short duration (5 weeks), not allowing any solid conclusion. Nevertheless, this study reported a reduction in plasma apoB, LDL-C, TAG, HDL-C, together with weight loss, in ten postmenopausal women following an ad libitum Palaeolithic diet( 208 ), which may be related to the high MUFA and PUFA and low CHO and SFA content of this diet. More RCT are needed exploring the effects of a Palaeolithic diet in comparison with a Western diet or healthy dietary patterns on plasma apoB and other lipoprotein parameters in various populations.


We analysed eighty-seven recent original studies published within the past 10 years on the concomitant modulation of plasma apoB and other lipoprotein parameters by nutritional components and dietary patterns. When an effect of a dietary component or pattern was reported by the majority of ≥3 interventional studies, the effect was indicated as significant in Table 2. Effects derived from association studies were also highlighted.

Consistent data from seven studies, three of which were RCT, in a total of 335 overweight and obese healthy or hyperlipidaemic subjects indicated that plasma apoB was reduced with hypoenergetic diet-induced weight loss of 6 to 12 %, using diets composed of 5440–7110 kJ (1300–1700 kcal/d), 34–50 % CHO, 27–39 % fat, and 18–24 % protein( 41 47 ). Eleven interventional studies, eight of which were RCT, compared macronutrients in isoenergetic diets in a total of 1189 healthy or hyperlipidaemic subjects. These were the studies that compared the effects of different amounts of CHO (see the Carbohydrates section( 56 , 59 63 )) or replacing SFA by MUFA (see the MUFA and PUFA v. SFA section( 62 , 82 86 )). The diets that reduced plasma apoB over 3–24 weeks were composed of 26–51 % CHO, 26–46 % fat, 11–32 % protein, 10–27 % MUFA, 5–14 % PUFA and 7–13 % SFA. Notably, among these diets, those that used higher CHO also used higher MUFA and/or lower SFA; thus it is not clear which of these macronutrients has the largest effect on plasma apoB. Nevertheless, replacement of CHO in high- or moderate-CHO diet by MUFA, not SFA, decreased plasma apoB. Few studies were found comparing the effect of MUFA v. PUFA on plasma apoB; however, this may be due to the recent meta-analysis reporting the lack of difference between these two types of unsaturated FA( 81 ).

Five studies, including four RCT, reported that the intake of marine-source n-3 FA from natural fish sources (1·1–1·7 g/d) or supplementation (3·2–3·4 g/d, EPA:DHA, 1·2:1 or 4 g/d EPA alone) decreased plasma apoB( 98 , 101 , 103 105 ). This was examined mostly in hyperlipidaemic subjects (n 411). Additional effects of n-3 FA (3·4 g/l) on plasma apoB was reported with simvastatin( 99 ), but not with atorvastatin( 100 ). While fewer RCT exist (three or four per component), they indicate that enriching the diet with soluble fibre such as psyllium (about 8–20 g/d)( 76 79 ), phytosterols (about 2–4 g/d)( 76 , 78 , 133 ) or nuts (30–75 g/d)( 172 174 ) decreases plasma apoB (examined only in hyperlipidaemic subjects for psyllium and phytosterol). A high intake of trans-FA (4·3–9·1 %)( 115 , 116 ) has been reported to increase plasma apoB. However, with the worldwide recommendation to reduce trans-FA intake to <1 %, it is unlikely that these elevated doses represent usual consumption. While inconsistent data were found in eight RCT regarding the replacement of milk proteins with soya proteins (25–30 g/d)( 138 147 ), the effect of soya protein may be specific to patients with hyperlipidaemia. Differential regulation of plasma apoB and TAG v. non-HDL-C, LDL-C and VLDL-C by weight loss, moderate CHO and high n-3 FA intake was noted, as these appear to benefit plasma apoB and TAG only.

Solid evidence from five studies( 85 , 86 , 190 195 ), including two RCT( 190 192 ), in a total of 823 subjects mostly at risk for CVD indicates that following an isoenergetic Med diet decreases plasma apoB, LDL-C and TAG. Cross-sectional studies suggest that alcohol consumption( 154 157 ) and vegetarian diets( 198 200 ) are associated with lower plasma apoB in 20 547 and 2052 subjects, respectively. However, RCT are lacking to confirm these observations and clarify the quantities and types of alcohol with the biggest effect of plasma apoB. Few other studies examined the regulation of the plasma apoB:apoA1 ratio; thus findings were insufficient. No effect or insufficient data were found using specific dietary components (MCFA as oil or in dietary items, fructose v. glucose, α-cyclodextrin v. psyllium fibre, plant-derived PUFA α-linolenic acid, whey or cowpea protein), dietary patterns (DASH, Nordic or Palaeolithic diet), food items (soya products, barley, legumes, whole grains, buttermilk, milk fat, kiwifruit, tomato, garlic powder) and vitamins and minerals. Future RCT need to explore the effects of these dietary components and patterns on plasma apoB and apoB:apoA1, and confirm the beneficial roles of soya protein, moderate alcohol intake, and vegetarian diets in healthy and hyperlipidaemic subjects during weight-loss or weight-maintenance interventions.

In summary, the healthy dietary pattern with the strongest reported evidence to reduce plasma apoB is a Mediterranean diet. This is probably because it encompasses the overall macronutrient composition (moderate CHO and fat, high n-3 FA, MUFA and PUFA, low SFA, and moderate alcohol) and dietary components (high psyllium, phytosterols and nuts) individually observed to reduce plasma apoB in the present review. It is this overall dietary pattern of a Mediterranean diet, rather than its individual components, that needs to be encouraged for optimal nutritional management of hyperapoB and for reducing the risk of CVD and T2D in humans.


The present review is supported by an operating grant from the Canadian Institute of Health Research (CIHR, MOP# 93581) to M. F.; M. F. is the recipient of salary support from the CIHR and Fonds de recherche du Québec (FRQ); V. L. is the recipient of a Vanier Canada Graduate Scholarship.

V. L. and M. F. conducted the literature review and manuscript writing; A. S. and M. F. reviewed and edited the manuscript. All authors read and approved the final manuscript.

There are no conflicts of interest.


1. Anderson, TJ, Gregoire, J, Hegele, RA, et al. (2013) 2012 Update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 29, 151167.
2. Lewis, GF, Uffelman, KD, Szeto, LW, et al. (1993) Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. Diabetes 42, 833842.
3. Malmstrom, R, Packard, CJ, Caslake, M, et al. (1997) Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia 40, 454462.
4. Ginsberg, HN, Zhang, YL & Hernandez-Ono, A (2005) Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res 36, 232240.
5. Sniderman, AD, St-Pierre, AC, Cantin, B, et al. (2003) Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk. Am J Cardiol 91, 11731177.
6. Sniderman, A, Shapiro, S, Marpole, D, et al. (1980) Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc Natl Acad Sci U S A 77, 604608.
7. Connelly, PW, Poapst, M, Davignon, J, et al. (1999) Reference values of plasma apolipoproteins A-I and B, and association with nonlipid risk factors in the populations of two Canadian provinces: Quebec and Saskatchewan. Canadian Heart Health Surveys Research Group. Can J Cardiol 15, 409418.
8. Holewijn, S, Sniderman, AD, den Heijer, M, et al. (2011) Application and validation of a diagnostic algorithm for the atherogenic apoB dyslipoproteinemias: ApoB dyslipoproteinemias in a Dutch population-based study. Eur J Clin Invest 41, 423433.
9. Sniderman, AD, Williams, K, Contois, JH, et al. (2011) A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes 4, 337345.
10. Contois, JH, McConnell, JP, Sethi, AA, et al. (2009) Apolipoprotein B and cardiovascular disease risk: position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices. Clin Chem 55, 407419.
11. Genest, J, McPherson, R, Frohlich, J, et al. (2009) 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations. Can J Cardiol 25, 567579.
12. Anderson, TJ, Gregoire, J, Hegele, RA, et al. (2014) Are the ACC/AHA guidelines on the treatment of blood cholesterol a game changer? A perspective from the Canadian Cardiovascular Society Dyslipidemia Panel. Can J Cardiol 30, 377380.
13. Catapano, AL, Reiner, Z, De Backer, G, et al. (2011) ESC/EAS Guidelines for the management of dyslipidaemias The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 217, 346.
14. Stone, NJ, Robinson, JG, Lichtenstein, AH, et al. (2014) 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 63, 28892934.
15. Pencina, MJ, D’Agostino, RB, Zdrojewski, T, et al. (2015) Apolipoprotein B improves risk assessment of future coronary heart disease in the Framingham Heart Study beyond LDL-C and non-HDL-C. Eur J Prev Cardiol 22, 13211327.
16. Sniderman, AD, Lamarche, B, Contois, JH, et al. (2014) Discordance analysis and the Gordian Knot of LDL and non-HDL cholesterol versus apoB. Curr Opin Lipidol 25, 461467.
17. Williams, KJ & Tabas, I (2005) Lipoprotein retention – and clues for atheroma regression. Arterioscler Thromb Vasc Biol 25, 15361540.
18. Fan, J & Watanabe, T (2003) Inflammatory reactions in the pathogenesis of atherosclerosis. J Atheroscler Thromb 10, 6371.
19. Faraj, M, Messier, L, Bastard, JP, et al. (2006) Apolipoprotein B: a predictor of inflammatory status in postmenopausal overweight and obese women. Diabetologia 49, 16371646.
20. Ridker, PM, Rifai, N, Rose, L, et al. (2002) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347, 15571565.
21. Schlitt, A, Blankenberg, S, Bickel, C, et al. (2005) Prognostic value of lipoproteins and their relation to inflammatory markers among patients with coronary artery disease. Int J Cardiol 102, 477485.
22. Bermudez, EA, Rifai, N, Buring, J, et al. (2002) Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol 22, 16681673.
23. Wassef, H, Bissonnette, S, Saint-Pierre, N, et al. (2015) The apoB-to-PCSK9 ratio: a new index for metabolic risk in humans. J Clin Lipidol 9, 664675.
24. Bissonnette, S, Salem, H, Wassef, H, et al. (2013) Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue. J Lipid Res 54, 14661476.
25. Bissonnette, S, Saint-Pierre, N, Lamantia, V, et al. (2015) Plasma IL-1Ra: linking hyperapoB to risk factors for type 2 diabetes independent of obesity in humans. Nutr Diabetes 5, e180.
26. Onat, A, Can, G, Hergenc, G, et al. (2007) Serum apolipoprotein B predicts dyslipidemia, metabolic syndrome and, in women, hypertension and diabetes, independent of markers of central obesity and inflammation. Int J Obes (Lond) 31, 11191125.
27. Ley, SH, Harris, SB, Connelly, PW, et al. (2010) Association of apolipoprotein B with incident type 2 diabetes in an aboriginal Canadian population. Clin Chem 56, 666670.
28. Salomaa, V, Havulinna, A, Saarela, O, et al. (2010) Thirty-one novel biomarkers as predictors for clinically incident diabetes. PLoS ONE 5, e10100.
29. Hwang, YC, Ahn, HY, Park, SW, et al. (2014) Apolipoprotein B and non-HDL cholesterol are more powerful predictors for incident type 2 diabetes than fasting glucose or glycated hemoglobin in subjects with normal glucose tolerance: a 3.3-year retrospective longitudinal study. Acta Diabetol 51, 941946.
30. Lamarche, B & Couture, P (2015) Dietary fatty acids, dietary patterns, and lipoprotein metabolism. Curr Opin Lipidol 26, 4247.
31. Ooi, EM, Ng, TW, Watts, GF, et al. (2013) Dietary fatty acids and lipoprotein metabolism: new insights and updates. Curr Opin Lipidol 24, 192197.
32. Chan, DC, Barrett, PH & Watts, GF (2014) The metabolic and pharmacologic bases for treating atherogenic dyslipidaemia. Best Pract Res Clin Endocrinol Metab 28, 369385.
33. Gammon, CS, Minihane, AM, Kruger, R, et al. (2014) TaqIB polymorphism in the cholesteryl ester transfer protein (CETP) gene influences lipid responses to the consumption of kiwifruit in hypercholesterolaemic men. Br J Nutr 111, 10771084.
34. Gammon, CS, Kruger, R, Minihane, AM, et al. (2013) Kiwifruit consumption favourably affects plasma lipids in a randomised controlled trial in hypercholesterolaemic men. Br J Nutr 109, 22082218.
35. Hu, M, Li, Z & Fang, DZ (2012) A high-carbohydrate diet effects on the A allele of hepatic lipase polymorphism on the apoB100/apoAI ratio in young Chinese males. Adv Clin Exp Med 21, 751757.
36. Curti, ML, Rogero, MM, Baltar, VT, et al. (2013) FTO T/A and peroxisome proliferator-activated receptor-γ Pro12Ala polymorphisms but not ApoA1 -75 are associated with better response to lifestyle intervention in Brazilians at high cardiometabolic risk. Metab Syndr Relat Disord 11, 169176.
37. Feinman, RD, Pogozelski, WK, Astrup, A, et al. (2015) Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 31, 113.
38. Tuomilehto, J, Lindstrom, J, Eriksson, JG, et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344, 13431350.
39. Dattilo, AM & Kris-Etherton, PM (1992) Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr 56, 320328.
40. Poobalan, A, Aucott, L, Smith, WC, et al. (2004) Effects of weight loss in overweight/obese individuals and long-term lipid outcomes – a systematic review. Obes Rev 5, 4350.
41. Chan, DC, Watts, GF, Gan, SK, et al. (2010) Effect of ezetimibe on hepatic fat, inflammatory markers, and apolipoprotein B-100 kinetics in insulin-resistant obese subjects on a weight loss diet. Diabetes Care 33, 11341139.
42. Faraj, M, Lavoie, ME, Messier, L, et al. (2010) Reduction in serum apoB is associated with reduced inflammation and insulin resistance in post-menopausal women: a MONET study. Atherosclerosis 211, 682688.
43. Ng, TW, Watts, GF, Barrett, PH, et al. (2007) Effect of weight loss on LDL and HDL kinetics in the metabolic syndrome: associations with changes in plasma retinol-binding protein-4 and adiponectin levels. Diabetes Care 30, 29452950.
44. de la Iglesia, R, Lopez-Legarrea, P, Crujeiras, AB, et al. (2014) Plasma irisin depletion under energy restriction is associated with improvements in lipid profile in metabolic syndrome patients. Clin Endocrinol (Oxf) 81, 306311.
45. Valente, EA, Sheehy, ME, Avila, JJ, et al. (2011) The effect of the addition of resistance training to a dietary education intervention on apolipoproteins and diet quality in overweight and obese older adults. Clin Interv Aging 6, 235241.
46. Vasudevan, M, Tchoua, U, Gillard, BK, et al. (2013) Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma of patients with metabolic syndrome. J Clin Lipidol 7, 661670.
47. Pelletier-Beaumont, E, Arsenault, BJ, Almeras, N, et al. (2012) Normalization of visceral adiposity is required to normalize plasma apolipoprotein B levels in response to a healthy eating/physical activity lifestyle modification program in viscerally obese men. Atherosclerosis 221, 577582.
48. Lavoie, ME, Faraj, M, Strychar, I, et al. (2013) Synergistic associations of physical activity and diet quality on cardiometabolic risk factors in overweight and obese postmenopausal women. Br J Nutr 109, 605614.
49. Haghighatdoost, F, Sarrafzadegan, N, Mohammadifard, N, et al. (2013) Healthy eating index and cardiovascular risk factors among Iranians. J Am Coll Nutr 32, 111121.
50. Health Canada (2011) Eating Well with Canada’s Food Guide: A Resource for Educators and Communicators. Ottawa: Health Canada.
51. Hellwig, JP, Otten, JJ, Meyers, LD, et al. (2006) Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: National Academies Press.
52. United States Department of Agriculture and United States Deparment of Health and Human Services (2010) Dietary Guidelines for Americans 2010, 7th ed. Washington, DC: United States Government Printing Office.
53. Parks, EJ (2001) Effect of dietary carbohydrate on triglyceride metabolism in humans. J Nutr 131, 2772s2774s.
54. Lichtenstein, AH (2006) Thematic review series: patient-oriented research. Dietary fat, carbohydrate, and protein: effects on plasma lipoprotein patterns. J Lipid Res 47, 16611667.
55. Schwingshackl, L & Hoffmann, G (2013) Comparison of effects of long-term low-fat vs high-fat diets on blood lipid levels in overweight or obese patients: a systematic review and meta-analysis. J Acad Nutr Diet 113, 16401661.
56. Shin, MJ, Blanche, PJ, Rawlings, RS, et al. (2007) Increased plasma concentrations of lipoprotein(a) during a low-fat, high-carbohydrate diet are associated with increased plasma concentrations of apolipoprotein C-III bound to apolipoprotein B-containing lipoproteins. Am J Clin Nutr 85, 15271532.
57. Parks, EJ & Hellerstein, MK (2000) Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms. Am J Clin Nutr 71, 412433.
58. Sacks, FM (2006) The apolipoprotein story. Atheroscler Suppl 7, 2327.
59. Krauss, RM, Blanche, PJ, Rawlings, RS, et al. (2006) Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 83, 10251031; quiz 1205.
60. Labonte, ME, Jenkins, DJ, Lewis, GF, et al. (2013) Adding MUFA to a dietary portfolio of cholesterol-lowering foods reduces apoAI fractional catabolic rate in subjects with dyslipidaemia. Br J Nutr 110, 426436.
61. Faghihnia, N, Tsimikas, S, Miller, ER, et al. (2010) Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet. J Lipid Res 51, 33243330.
62. Mangravite, LM, Chiu, S, Wojnoonski, K, et al. (2011) Changes in atherogenic dyslipidemia induced by carbohydrate restriction in men are dependent on dietary protein source. J Nutr 141, 21802185.
63. Mercanligil, SM, Arslan, P, Alasalvar, C, et al. (2007) Effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles in hypercholesterolemic adult men. Eur J Clin Nutr 61, 212220.
64. Brinkworth, GD, Noakes, M, Buckley, JD, et al. (2009) Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Am J Clin Nutr 90, 2332.
65. Tay, J, Brinkworth, GD, Noakes, M, et al. (2008) Metabolic effects of weight loss on a very-low-carbohydrate diet compared with an isocaloric high-carbohydrate diet in abdominally obese subjects. J Am Coll Cardiol 51, 5967.
66. Miller, M, Beach, V, Sorkin, JD, et al. (2009) Comparative effects of three popular diets on lipids, endothelial function, and C-reactive protein during weight maintenance. J Am Diet Assoc 109, 713717.
67. Keogh, JB, Grieger, JA, Noakes, M, et al. (2005) Flow-mediated dilatation is impaired by a high-saturated fat diet but not by a high-carbohydrate diet. Arterioscler Thromb Vasc Biol 25, 12741279.
68. Johnson, RK, Appel, LJ, Brands, M, et al. (2009) Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation 120, 10111020.
69. Swarbrick, MM, Stanhope, KL, Elliott, SS, et al. (2008) Consumption of fructose-sweetened beverages for 10 weeks increases postprandial triacylglycerol and apolipoprotein-B concentrations in overweight and obese women. Br J Nutr 100, 947952.
70. Semenkovich, CF (2006) Insulin resistance and atherosclerosis. J Clin Invest 116, 18131822.
71. Stanhope, KL, Bremer, AA, Medici, V, et al. (2011) Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women. J Clin Endocrinol Metab 96, E1596E1605.
72. Lattimer, JM & Haub, MD (2010) Effects of dietary fiber and its components on metabolic health. Nutrients 2, 12661289.
73. Theuwissen, E & Mensink, RP (2008) Water-soluble dietary fibers and cardiovascular disease. Physiol Behav 94, 285292.
74. Fernandez, ML, Vergara-Jimenez, M, Conde, K, et al. (1997) Regulation of apolipoprotein B-containing lipoproteins by dietary soluble fiber in guinea pigs. Am J Clin Nutr 65, 814822.
75. National Cholesterol Education Program (NCEP) Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106, 31433421.
76. Shrestha, S, Volek, JS, Udani, J, et al. (2006) A combination therapy including psyllium and plant sterols lowers LDL cholesterol by modifying lipoprotein metabolism in hypercholesterolemic individuals. J Nutr 136, 24922497.
77. Moreyra, AE, Wilson, AC & Koraym, A (2005) Effect of combining psyllium fiber with simvastatin in lowering cholesterol. Arch Intern Med 165, 11611166.
78. Sola, R, Valls, RM, Godas, G, et al. (2012) Cocoa, hazelnuts, sterols and soluble fiber cream reduces lipids and inflammation biomarkers in hypertensive patients: a randomized controlled trial. PLOS ONE 7, e31103.
79. Comerford, KB, Artiss, JD, Jen, KL, et al. (2011) The beneficial effects of α-cyclodextrin on blood lipids and weight loss in healthy humans. Obesity (Silver Spring) 19, 12001204.
80. Food and Agriculture Organization of the United Nations (2010) Fats and Fatty Acids in Human Nutrition: Report of an Expert Consultation, no. 9789251067338]. Geneva: Food and Agriculture Organization of the United Nations.
81. Mozaffarian, D & Clarke, R (2009) Quantitative effects on cardiovascular risk factors and coronary heart disease risk of replacing partially hydrogenated vegetable oils with other fats and oils. Eur J Clin Nutr 63, Suppl. 2, S22S33.
82. Jebb, SA, Lovegrove, JA, Griffin, BA, et al. (2010) Effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk: the RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial. Am J Clin Nutr 92, 748758.
83. Berglund, L, Lefevre, M, Ginsberg, HN, et al. (2007) Comparison of monounsaturated fat with carbohydrates as a replacement for saturated fat in subjects with a high metabolic risk profile: studies in the fasting and postprandial states. Am J Clin Nutr 86, 16111620.
84. Allman-Farinelli, MA, Gomes, K, Favaloro, EJ, et al. (2005) A diet rich in high-oleic-acid sunflower oil favorably alters low-density lipoprotein cholesterol, triglycerides, and factor VII coagulant activity. J Am Diet Assoc 105, 10711079.
85. van Dijk, SJ, Feskens, EJ, Bos, MB, et al. (2012) Consumption of a high monounsaturated fat diet reduces oxidative phosphorylation gene expression in peripheral blood mononuclear cells of abdominally overweight men and women. J Nutr 142, 12191225.
86. Bos, MB, de Vries, JH, Feskens, EJ, et al. (2010) Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity. Nutr Metab Cardiovasc Dis 20, 591598.
87. Binkoski, AE, Kris-Etherton, PM, Wilson, TA, et al. (2005) Balance of unsaturated fatty acids is important to a cholesterol-lowering diet: comparison of mid-oleic sunflower oil and olive oil on cardiovascular disease risk factors. J Am Diet Assoc 105, 10801086.
88. Lee, JY, Zhao, L & Hwang, DH (2010) Modulation of pattern recognition receptor-mediated inflammation and risk of chronic diseases by dietary fatty acids. Nutr Rev 68, 3861.
89. Flock, MR, Green, MH & Kris-Etherton, PM (2011) Effects of adiposity on plasma lipid response to reductions in dietary saturated fatty acids and cholesterol. Adv Nutr 2, 261274.
90. Schwartz, EA, Zhang, WY, Karnik, SK, et al. (2010) Nutrient modification of the innate immune response: a novel mechanism by which saturated fatty acids greatly amplify monocyte inflammation. Arterioscler Thromb Vasc Biol 30, 802808.
91. Chait, A & Kim, F (2010) Saturated fatty acids and inflammation: who pays the toll? Arterioscler Thromb Vasc Biol 30, 692693.
92. Mustad, VA, Etherton, TD, Cooper, AD, et al. (1997) Reducing saturated fat intake is associated with increased levels of LDL receptors on mononuclear cells in healthy men and women. J Lipid Res 38, 459468.
93. Santos, S, Oliveira, A & Lopes, C (2013) Systematic review of saturated fatty acids on inflammation and circulating levels of adipokines. Nutr Res 33, 687695.
94. Teng, KT, Chang, CY, Chang, LF, et al. (2014) Modulation of obesity-induced inflammation by dietary fats: mechanisms and clinical evidence. Nutr J 13, 12.
95. Cave, MC, Hurt, RT, Frazier, TH, et al. (2008) Obesity, inflammation, and the potential application of pharmaconutrition. Nutr Clin Pract 23, 1634.
96. Bays, HE, Tighe, AP, Sadovsky, R, et al. (2008) Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther 6, 391409.
97. Kris-Etherton, PM, Harris, WS & Appel, LJ (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 27472757.
98. Bays, HE, Ballantyne, CM, Kastelein, JJ, et al. (2011) Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol 108, 682690.
99. Davidson, MH, Stein, EA, Bays, HE, et al. (2007) Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther 29, 13541367.
100. Bays, HE, McKenney, J, Maki, KC, et al. (2010) Effects of prescription omega-3-acid ethyl esters on non--high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc 85, 122128.
101. Zhang, J, Wang, C, Li, L, et al. (2012) Dietary inclusion of salmon, herring and pompano as oily fish reduces CVD risk markers in dyslipidaemic middle-aged and elderly Chinese women. Br J Nutr 108, 14551465.
102. Lee, SP, Dart, AM, Walker, KZ, et al. (2012) Effect of altering dietary n-6:n-3 PUFA ratio on cardiovascular risk measures in patients treated with statins: a pilot study. Br J Nutr 108, 12801285.
103. Wong, AT, Chan, DC, Ooi, EM, et al. (2013) Omega-3 fatty acid ethyl ester supplementation decreases very-low-density lipoprotein triacylglycerol secretion in obese men. Clin Sci (Lond) 125, 4551.
104. Wong, AT, Chan, DC, Barrett, PH, et al. (2014) Effect of omega-3 fatty acid ethyl esters on apolipoprotein B-48 kinetics in obese subjects on a weight-loss diet: a new tracer kinetic study in the postprandial state. J Clin Endocrinol Metab 99, E1427E1435.
105. Ooi, EM, Lichtenstein, AH, Millar, JS, et al. (2012) Effects of therapeutic lifestyle change diets high and low in dietary fish-derived FAs on lipoprotein metabolism in middle-aged and elderly subjects. J Lipid Res 53, 19581967.
106. Forster, LF, Stewart, G, Bedford, D, et al. (2002) Influence of atorvastatin and simvastatin on apolipoprotein B metabolism in moderate combined hyperlipidemic subjects with low VLDL and LDL fractional clearance rates. Atherosclerosis 164, 129145.
107. Karalis, DG, Ross, AM, Vacari, RM, et al. (2002) Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease. Am J Cardiol 89, 667671.
108. Watts, GF, Chan, DC, Ooi, EM, et al. (2006) Fish oils, phytosterols and weight loss in the regulation of lipoprotein transport in the metabolic syndrome: lessons from stable isotope tracer studies. Clin Exp Pharmacol Physiol 33, 877882.
109. Pan, M, Maitin, V, Parathath, S, et al. (2008) Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality control. Proc Natl Acad Sci U S A 105, 58625867.
110. Pan, A, Chen, M, Chowdhury, R, et al. (2012) α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr 96, 12621273.
111. Institute of Medicine (2002) Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids . Washington, DC: National Academies Press.
112. Dodin, S, Cunnane, SC, Masse, B, et al. (2008) Flaxseed on cardiovascular disease markers in healthy menopausal women: a randomized, double-blind, placebo-controlled trial. Nutrition 24, 2330.
113. Dodin, S, Lemay, A, Jacques, H, et al. (2005) The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. J Clin Endocrinol Metab 90, 13901397.
114. Brenna, JT, Salem, N Jr., Sinclair, AJ, et al. (2009) α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 80, 8591.
115. Vega-López, S, Matthan, NR, Ausman, LM, et al. (2009) Substitution of vegetable oil for a partially-hydrogenated fat favorably alters cardiovascular disease risk factors in moderately hypercholesterolemic postmenopausal women. Atherosclerosis 207, 208212.
116. Wanders, AJ, Brouwer, IA, Siebelink, E, et al. (2010) Effect of a high intake of conjugated linoleic acid on lipoprotein levels in healthy human subjects. PLoS ONE 5, e9000.
117. Martin, CA, Milinsk, MC, Visentainer, JV, et al. (2007) Trans fatty acid-forming processes in foods: a review. An Acad Bras Cienc 79, 343350.
118. Brouwer, IA, Wanders, AJ & Katan, MB (2013) Trans fatty acids and cardiovascular health: research completed? Eur J Clin Nutr 67, 541547.
119. Chardigny, JM, Destaillats, F, Malpuech-Brugere, C, et al. (2008) Do trans fatty acids from industrially produced sources and from natural sources have the same effect on cardiovascular disease risk factors in healthy subjects? Results of the trans Fatty Acids Collaboration (TRANSFACT) study. Am J Clin Nutr 87, 558566.
120. Health Canada (2009) General Questions and Answers on Trans Fat. (accessed February 2016).
121. United States Food and Drug Administration (2015) The FDA takes step to remove artificial trans fats in processed foods. (accessed June 2016).
122. Rouis, M, Dugi, KA, Previato, L, et al. (1997) Therapeutic response to medium-chain triglycerides and omega-3 fatty acids in a patient with the familial chylomicronemia syndrome. Arterioscler Thromb Vasc Biol 17, 14001406.
123. Tremblay, AJ, Lamarche, B, Labonte, ME, et al. (2014) Dietary medium-chain triglyceride supplementation has no effect on apolipoprotein B-48 and apolipoprotein B-100 kinetics in insulin-resistant men. Am J Clin Nutr 99, 5461.
124. Bohl, M, Bjornshave, A, Rasmussen, KV, et al. (2015) Dairy proteins, dairy lipids, and postprandial lipemia in persons with abdominal obesity (DairyHealth): a 12-wk, randomized, parallel-controlled, double-blinded, diet intervention study. Am J Clin Nutr 101, 870878.
125. Rego Costa, AC, Rosado, EL & Soares-Mota, M (2012) Influence of the dietary intake of medium chain triglycerides on body composition, energy expenditure and satiety: a systematic review. Nutr Hosp 27, 103108.
126. Eckel, RH, Jakicic, JM, Ard, JD, et al. (2014) 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129, S76S99.
127. Cesar, TB, Oliveira, MR, Mesquita, CH, et al. (2006) High cholesterol intake modifies chylomicron metabolism in normolipidemic young men. J Nutr 136, 971976.
128. Pearce, KL, Clifton, PM & Noakes, M (2011) Egg consumption as part of an energy-restricted high-protein diet improves blood lipid and blood glucose profiles in individuals with type 2 diabetes. Br J Nutr 105, 584592.
129. AbuMweis, SS, Marinangeli, CP, Frohlich, J, et al. (2014) Implementing phytosterols into medical practice as a cholesterol-lowering strategy: overview of efficacy, effectiveness, and safety. Can J Cardiol 30, 12251232.
130. Demonty, I, Ras, RT, van der Knaap, HC, et al. (2009) Continuous dose–response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J Nutr 139, 271284.
131. Abumweis, SS, Barake, R & Jones, PJ (2008) Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials. Food Nutr Res 52, 10.3402/fnr.v52i0.1811.
132. Klingberg, S, Andersson, H, Mulligan, A, et al. (2008) Food sources of plant sterols in the EPIC Norfolk population. Eur J Clin Nutr 62, 695703.
133. Sialvera, TE, Pounis, GD, Koutelidakis, AE, et al. (2012) Phytosterols supplementation decreases plasma small and dense LDL levels in metabolic syndrome patients on a Westernized type diet. Nutr Metab Cardiovasc Dis 22, 843848.
134. Anderson, JW, Johnstone, BM & Cook-Newell, ME (1995) Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 333, 276282.
135. Anonymous (1999) Food labeling: health claims; soy protein and coronary heart disease. Food and Drug Administration, HHS. Final rule. Fed Regist 64, 5700057733.
136. Potter, SM (1995) Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J Nutr 125, 606s611s.
137. Baum, JA, Teng, H, Erdman, JW Jr, et al. (1998) Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am J Clin Nutr 68, 545551.
138. Campbell, SC, Khalil, DA, Payton, ME, et al. (2010) One-year soy protein supplementation does not improve lipid profile in postmenopausal women. Menopause 17, 587593.
139. Maki, KC, Butteiger, DN, Rains, TM, et al. (2010) Effects of soy protein on lipoprotein lipids and fecal bile acid excretion in men and women with moderate hypercholesterolemia. J Clin Lipidol 4, 531542.
140. Chen, ST, Ferng, SH, Yang, CS, et al. (2005) Variable effects of soy protein on plasma lipids in hyperlipidemic and normolipidemic hemodialysis patients. Am J Kidney Dis 46, 10991106.
141. Chen, ST, Chen, JR, Yang, CS, et al. (2006) Effect of soya protein on serum lipid profile and lipoprotein concentrations in patients undergoing hypercholesterolaemic haemodialysis. Br J Nutr 95, 366371.
142. Fanti, P, Sawaya, BP, Custer, LJ, et al. (1999) Serum levels and metabolic clearance of the isoflavones genistein and daidzein in hemodialysis patients. J Am Soc Nephrol 10, 864871.
143. Santo, AS, Santo, AM, Browne, RW, et al. (2010) Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. Lipids 45, 11271138.
144. Santo, AS, Cunningham, AM, Alhassan, S, et al. (2008) NMR analysis of lipoprotein particle size does not increase sensitivity to the effect of soy protein on CVD risk when compared with the traditional lipid profile. Appl Physiol Nutr Metab 33, 489500.
145. McVeigh, BL, Dillingham, BL, Lampe, JW, et al. (2006) Effect of soy protein varying in isoflavone content on serum lipids in healthy young men. Am J Clin Nutr 83, 244251.
146. Pipe, EA, Gobert, CP, Capes, SE, et al. (2009) Soy protein reduces serum LDL cholesterol and the LDL cholesterol:HDL cholesterol and apolipoprotein B:apolipoprotein A-I ratios in adults with type 2 diabetes. J Nutr 139, 17001706.
147. Kwak, JH, Ahn, CW, Park, SH, et al. (2012) Weight reduction effects of a black soy peptide supplement in overweight and obese subjects: double blind, randomized, controlled study. Food Funct 3, 10191024.
148. Axelson, M, Kirk, DN, Farrant, RD, et al. (1982) The identification of the weak oestrogen equol [7-hydroxy-3-(4’-hydroxyphenyl)chroman] in human urine. Biochem J 201, 353357.
149. Setchell, KD, Brown, NM & Lydeking-Olsen, E (2002) The clinical importance of the metabolite equol – a clue to the effectiveness of soy and its isoflavones. J Nutr 132, 35773584.
150. Barton, M (2013) Cholesterol and atherosclerosis: modulation by oestrogen. Curr Opin Lipidol 24, 214220.
151. Frota, KMG, dos Santos, RD, Ribeiro, VQ, et al. (2015) Cowpea protein reduces LDL-cholesterol and apolipoprotein B concentrations, but does not improve biomarkers of inflammation or endothelial dysfunction in adults with moderate hypercholesterolemia. Nutr Hosp 31, 16111619.
152. Pereira, PC (2014) Milk nutritional composition and its role in human health. Nutrition 30, 619627.
153. Butt, P, Beirness, D, Gliksman, L, et al. (2011) Alcohol and Health in Canada: A Summary of Evidence and Guidelines for Low Risk Drinking. Ottawa, ON: Canadian Centre on Substance Abuse.
154. Volcik, KA, Ballantyne, CM, Fuchs, FD, et al. (2008) Relationship of alcohol consumption and type of alcoholic beverage consumed with plasma lipid levels: differences between Whites and African Americans of the ARIC study. Ann Epidemiol 18, 101107.
155. Tognon, G, Berg, C, Mehlig, K, et al. (2012) Comparison of apolipoprotein (apoB/apoA-I) and lipoprotein (total cholesterol/HDL) ratio determinants. Focus on obesity, diet and alcohol intake. PLOS ONE 7, e40878.
156. Liangpunsakul, S, Qi, R, Crabb, DW, et al. (2010) Relationship between alcohol drinking and aspartate aminotransferase:alanine aminotransferase (AST:ALT) ratio, mean corpuscular volume (MCV), γ-glutamyl transpeptidase (GGT), and apolipoprotein A1 and B in the U.S. population. J Stud Alcohol Drugs 71, 249252.
157. Simonsson, M, Schmidt, C, Sigurdadottir, V, et al. (2007) Life style habits such as alcohol consumption and physical activity in relation to serum apoB/apoA-I ratio amongst 64-year-old women with varying degrees of glucose tolerance. J Intern Med 262, 537544.
158. Kawata, S, Fukuda, K, Inui, Y, et al. (1993) Molecular biology in development of fatty liver – regulation of apolipoprotein B synthesis [article in Japanese]. Nihon Rinsho 51, 414422.
159. Klop, B, do Rego, AT & Cabezas, MC (2013) Alcohol and plasma triglycerides. Curr Opin Lipidol 24, 321326.
160. Naissides, M, Mamo, JC, James, AP, et al. (2006) The effect of chronic consumption of red wine on cardiovascular disease risk factors in postmenopausal women. Atherosclerosis 185, 438445.
161. Pal, S, Ho, N, Santos, C, et al. (2003) Red wine polyphenolics increase LDL receptor expression and activity and suppress the secretion of ApoB100 from human HepG2 cells. J Nutr 133, 700706.
162. Pal, S, Ho, SS & Takechi, R (2005) Red wine polyphenolics suppress the secretion of ApoB48 from human intestinal CaCo-2 cells. J Agric Food Chem 53, 27672772.
163. Tomé-Carneiro, J, Gonzálvez, M, Larrosa, M, et al. (2012) Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Mol Nutr Food Res 56, 810821.
164. Martini, LA, Catania, AS & Ferreira, SR (2010) Role of vitamins and minerals in prevention and management of type 2 diabetes mellitus. Nutr Rev 68, 341354.
165. Montonen, J, Knekt, P, Jarvinen, R, et al. (2004) Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care 27, 362366.
166. Al-Daghri, NM, Alkharfy, KM, Al-Saleh, Y, et al. (2012) Modest reversal of metabolic syndrome manifestations with vitamin D status correction: a 12-month prospective study. Metabolism 61, 661666.
167. McGill, AT, Stewart, JM, Lithander, FE, et al. (2008) Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J 7, 4.
168. Czernichow, S, Vergnaud, AC, Galan, P, et al. (2009) Effects of long-term antioxidant supplementation and association of serum antioxidant concentrations with risk of metabolic syndrome in adults. Am J Clin Nutr 90, 329335.
169. Ros, E & Mataix, J (2006) Fatty acid composition of nuts – implications for cardiovascular health. Br J Nutr 96, Suppl. 2, S29S35.
170. Chen, CY & Blumberg, JB (2008) Phytochemical composition of nuts. Asia Pac J Clin Nutr 17, Suppl. 1, 329332.
171. Bahadoran, Z, Golzarand, M, Mirmiran, P, et al. (2013) The association of dietary phytochemical index and cardiometabolic risk factors in adults: Tehran Lipid and Glucose Study. J Hum Nutr Diet 26, Suppl. 1, 145153.
172. Jenkins, DJ, Kendall, CW, Banach, MS, et al. (2011) Nuts as a replacement for carbohydrates in the diabetic diet. Diabetes Care 34, 17061711.
173. Wu, L, Piotrowski, K, Rau, T, et al. (2014) Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: a randomized controlled cross-over clinical trial. Metabolism 63, 382391.
174. Tey, SL, Brown, RC, Chisholm, AW, et al. (2011) Effects of different forms of hazelnuts on blood lipids and α-tocopherol concentrations in mildly hypercholesterolemic individuals. Eur J Clin Nutr 65, 117124.
175. Zhang, X, Shu, XO, Gao, YT, et al. (2003) Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J Nutr 133, 28742878.
176. Nagata, C (2000) Ecological study of the association between soy product intake and mortality from cancer and heart disease in Japan. Int J Epidemiol 29, 832836.
177. Kokubo, Y, Iso, H, Ishihara, J, et al. (2007) Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations: the Japan Public Health Center-based (JPHC) study cohort I. Circulation 116, 25532562.
178. Welty, FK, Lee, KS, Lew, NS, et al. (2007) Effect of soy nuts on blood pressure and lipid levels in hypertensive, prehypertensive, and normotensive postmenopausal women. Arch Intern Med 167, 10601067.
179. Tabibi, H, Imani, H, Hedayati, M, et al. (2010) Effects of soy consumption on serum lipids and apoproteins in peritoneal dialysis patients: a randomized controlled trial. Perit Dial Int 30, 611618.
180. Back, HI, Kim, SR, Yang, JA, et al. (2011) Effects of Chungkookjang supplementation on obesity and atherosclerotic indices in overweight/obese subjects: a 12-week, randomized, double-blind, placebo-controlled clinical trial. J Med Food 14, 532537.
181. Hati, S, Vij, S, Singh, BP, et al. (2015) β-Glucosidase activity and bioconversion of isoflavones during fermentation of soymilk. J Sci Food Agric 95, 216220.
182. Tovar, J, Nilsson, A, Johansson, M, et al. (2014) Combining functional features of whole-grain barley and legumes for dietary reduction of cardiometabolic risk: a randomised cross-over intervention in mature women. Br J Nutr 111, 706714.
183. Giacco, R, Costabile, G, Della Pepa, G, et al. (2014) A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome. Nutr Metab Cardiovasc Dis 24, 837844.
184. Drouin-Chartier, JP, Gagnon, J, Labonte, ME, et al. (2015) Impact of milk consumption on cardiometabolic risk in postmenopausal women with abdominal obesity. Nutr J 14, 12.
185. Conway, V, Couture, P, Richard, C, et al. (2013) Impact of buttermilk consumption on plasma lipids and surrogate markers of cholesterol homeostasis in men and women. Nutr Metab Cardiovasc Dis 23, 12551262.
186. Gammon, CS, Kruger, R, Conlon, CA, et al. (2014) Inflammatory status modulates plasma lipid and inflammatory marker responses to kiwifruit consumption in hypercholesterolaemic men. Nutr Metab Cardiovasc Dis 24, 9199.
187. Shidfar, F, Froghifar, N, Vafa, M, et al. (2011) The effects of tomato consumption on serum glucose, apolipoprotein B, apolipoprotein A-I, homocysteine and blood pressure in type 2 diabetic patients. Int J Food Sci Nutr 62, 289294.
188. Mahdavi-Roshan, M, Zahedmehr, A, Mohammad-Zadeh, A, et al. (2013) Effect of garlic powder tablet on carotid intima-media thickness in patients with coronary artery disease: a preliminary randomized controlled trial. Nutr Health 22, 143155.
189. Willett, WC, Sacks, F, Trichopoulou, A, et al. (1995) Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr 61, 1402s1406s.
190. Sola, R, Fito, M, Estruch, R, et al. (2011) Effect of a traditional Mediterranean diet on apolipoproteins B, A-I, and their ratio: a randomized, controlled trial. Atherosclerosis 218, 174180.
191. Defoort, C, Vincent-Baudry, S & Lairon, D (2011) Effects of 3-month Mediterranean-type diet on postprandial TAG and apolipoprotein B48 in the Medi-RIVAGE cohort. Public Health Nutr 14, 23022308.
192. Vincent-Baudry, S, Defoort, C, Gerber, M, et al. (2005) The Medi-RIVAGE study: reduction of cardiovascular disease risk factors after a 3-mo intervention with a Mediterranean-type diet or a low-fat diet. Am J Clin Nutr 82, 964971.
193. Bedard, A, Riverin, M, Dodin, S, et al. (2012) Sex differences in the impact of the Mediterranean diet on cardiovascular risk profile. Br J Nutr 108, 14281434.
194. Richard, C, Couture, P, Desroches, S, et al. (2011) Effect of the Mediterranean diet with and without weight loss on cardiovascular risk factors in men with the metabolic syndrome. Nutr Metab Cardiovasc Dis 21, 628635.
195. Richard, C, Couture, P, Ooi, EM, et al. (2014) Effect of Mediterranean diet with and without weight loss on apolipoprotein B100 metabolism in men with metabolic syndrome. Arterioscler Thromb Vasc Biol 34, 433438.
196. Sotos-Prieto, M, Luben, R, Khaw, KT, et al. (2014) The association between Mediterranean Diet Score and glucokinase regulatory protein gene variation on the markers of cardiometabolic risk: an analysis in the European Prospective Investigation into Cancer (EPIC)-Norfolk study. Br J Nutr 112, 122131.
197. Beltaifa, L, Chaouachi, A, Zerifi, R, et al. (2011) Walk–run transition speed training as an efficient exercise adjunct to dietary restriction in the management of obesity: a prospective intervention pilot study. Obes Facts 4, 4552.
198. Zhang, HJ, Han, P, Sun, SY, et al. (2013) Attenuated associations between increasing BMI and unfavorable lipid profiles in Chinese Buddhist vegetarians. Asia Pac J Clin Nutr 22, 249256.
199. Bradbury, KE, Crowe, FL, Appleby, PN, et al. (2014) Serum concentrations of cholesterol, apolipoprotein A-I and apolipoprotein B in a total of 1694 meat-eaters, fish-eaters, vegetarians and vegans. Eur J Clin Nutr 68, 178183.
200. Karelis, AD, Fex, A, Filion, ME, et al. (2010) Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women. Br J Nutr 104, 222226.
201. Maiyoh, GK, Kuh, JE, Casaschi, A, et al. (2007) Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells. J Nutr 137, 21852189.
202. Olsen, A, Egeberg, R, Halkjaer, J, et al. (2011) Healthy aspects of the Nordic diet are related to lower total mortality. J Nutr 141, 639644.
203. Adamsson, V, Reumark, A, Fredriksson, IB, et al. (2011) Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET). J Intern Med 269, 150159.
204. Uusitupa, M, Hermansen, K, Savolainen, MJ, et al. (2013) Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome – a randomized study (SYSDIET). J Intern Med 274, 5266.
205. Hodson, L, Harnden, KE, Roberts, R, et al. (2010) Does the DASH diet lower blood pressure by altering peripheral vascular function? J Hum Hypertens 24, 312319.
206. Krikken, JA, Dallinga-Thie, GM, Navis, G, et al. (2012) Short term dietary sodium restriction decreases HDL cholesterol, apolipoprotein A-I and high molecular weight adiponectin in healthy young men: relationships with renal hemodynamics and RAAS activation. Nutr Metab Cardiovasc Dis 22, 3541.
207. Frassetto, LA, Schloetter, M, Mietus-Synder, M, et al. (2009) Metabolic and physiologic improvements from consuming a Paleolithic, hunter–gatherer type diet. Eur J Clin Nutr 63, 947955.
208. Ryberg, M, Sandberg, S, Mellberg, C, et al. (2013) A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women. J Intern Med 274, 6776.