Primary Prevention of CVD- Diet and Weight Loss

Primary prevention of CVD: diet and weight lossSearch date August 2006Lee Hooper

QUESTIONS

What are the effects of interventions in the general population to reduce sodium intake?. . . . . . . . . . . . . . . . . . 3

What are the effects of a cholesterol-lowering diet in the general population?. . . . . . . . . . . . . . . . . . . . . . . . . . 5

What are the effects of interventions to increase or maintain weight loss?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

What are the effects on reducing CVD risk in the general population of eating more fruit and vegetables?. . . 10

What are the effects on reducing CVD risk of antioxidants in the general population?. . . . . . . . . . . . . . . . . . . 10

What are the effects on reduction of CVD risk of omega 3 fatty acids in the general population?. . . . . . . . . . . 12

What are the effects on reduction of CVD risk of a Mediterranean diet in the general population?. . . . . . . . . . 12

INTERVENTIONS

ADVICE PROMOTING REDUCTION IN SALT INTAKE

Beneficial

Advice to reduce sodium intake: reduction in cardiovas-cular disease risk New . . . . . . . . . . . . . . . . . . . . . . 3

Likely to be beneficial

Advice to reduce sodium intake: reduction in sodium in-take New . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

ADVICE PROMOTING CHOLESTEROL-LOWERING


Advice to reduce saturated fat intake: reduction in car-diovascular disease risk New . . . . . . . . . . . . . . . . . 5

Advice to reduce saturated fat intake: reduction in fatintake New . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

REDUCING WEIGHT OR MAINTAINING WEIGHTLOSS

Beneficial

Diets and behavioural interventions to lose weight:weight loss (effective in combination but not alone) New. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Unknown effectiveness

Diets and behavioural interventions: reduction in cardio-vascular risk New . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Lifestyle interventions: maintainance of weight loss New. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Lifestyle interventions: preventing weight gain New . .8

Training health professionals in promoting weight loss:weight loss New . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

INCREASING FRUIT AND VEGETABLE INTAKE


Increase fruit and vegetable intake: reduction in cardio-vascular disease risk New . . . . . . . . . . . . . . . . . . . 10


Behavioural and counselling interventions: increase infruit and vegetable intake New . . . . . . . . . . . . . . . 10

ANTIOXIDANTS

Unlikely to be beneficial

High-dose antioxidant supplements: reduction in cardio-vascular risk New . . . . . . . . . . . . . . . . . . . . . . . . . 10

OMEGA 3


Omega 3 fatty acids: reduction in cardiovascular riskNew . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

MEDITERRANEAN DIET


Mediterranean diet: reduction in cardiovascular riskNew . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Covered elsewhere in Clinical Evidence

Primary prevention of CVD: physical activity

Key points

• Diet is an important cause of many chronic diseases.

Individual change in behaviour has the potential to decrease the burden of chronic disease, particularly cardio-vascular disease (CVD).

This review focuses on the evidence that specific interventions to improve diet and increase weight loss lead tochanged behaviour, and that these changes may prevent CVD.

• Intensive advice to healthy people to reduce sodium intake reduces sodium intake, as measured by sodium excretion.

Blo

od

and

lymp

h d

isord

ers

© BMJ Publishing Group Ltd 2007. All rights reserved. . . . . . . . . . . . . . . . . . . . . . 1 . . . . . . . . . . . . . . . . . . . . . Clinical Evidence 2007;10:219

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

• Reducing sodium intake reduces blood pressure, even in people without hypertension.

• Advice to reduce saturated fat intake may reduce the saturated fat intake, and multiple advice components reducesaturated fat intake more.

• Reducing saturated fat intake can reduce mortality in the longer term.

• Complex combined interventions to lose weight (physical plus dietary plus behavioural) are effective in helpingpeople lose weight. Simpler interventions are less effective.

We don't know what lifestyle interventions can maintain weight loss or what lifestyle interventions prevent weightgain, or if training health professionals is effective in promoting weight loss.

We don't know whether diets and behavioural interventions to lose weight reduce the risk of cardiovascular disease.

• Increasing fruit and vegetable intake may decrease the risk of cardiovascular disease.

We don't know whether advising people to increase their fruit and vegetable intake will actually increase theirintake.

• Taking a high dose of antioxidant supplements (vitamin E and beta carotene) does not reduce mortality or cardio-vascular events.

• We don't know whether omega 3 oil supplementation or advice to increase omega 3 intake can reduce mortality.

• We also don't know how effective a Mediterranean diet is at reducing cardiovascular events or deaths in the gen-eral population.

DEFINITION Diet is important in the cause of many chronic diseases. Individual change in behaviour has thepotential to decrease the burden of chronic disease, particularly cardiovascular disease (CVD).This review focuses on the evidence that specific interventions to improve diet and increase weightloss lead to changed behaviour, and that these changes may prevent CVD. Primary prevention inthis context is the long-term management of people at increased risk but with no evidence of CVD.Clinically overt ischaemic vascular disease includes acute myocardial infarction, angina, stroke,and peripheral vascular disease. Many adults have no symptoms or obvious signs of vasculardisease, even though they have atheroma and are at increased risk of ischaemic vascular eventsbecause of one or more risk factors. In this review, we have taken primary prevention to apply topeople who have not had clinically overt CVD, or people at low risk of ischaemic cardiovascularevents. Prevention of cerebrovascular events is discussed in detail elsewhere in BMJ Clinical Evi-dence (see review on stroke prevention).

INCIDENCE/PREVALENCE

CVD was responsible for 39% of UK deaths in 2002. Half of these were from coronary heart disease(CHD), and a quarter from stroke. CVD is also a major cause of death before 75 years of age,causing 34% of early deaths in men and 25% of deaths before 75 years of age in women. CHDdeaths rose dramatically in the UK during the 20th century, peaked in the 1970s, and have fallensince then. Numbers of people living with CVD are not falling, and the British Heart Foundationestimates that there are about 1.5 million men and 1.2 million women who have or have had amyocardial infarction or angina. [1] Worldwide, it is estimated that 17 million people die of CVDsevery year, and more than 60% of the global burden of CHD is found in resource-poor countries(10% of disability-adjusted life years [DALYs] lost in low- and middle-income countries and 18%in high-income countries). [2] The USA has a similar burden of heart disease to the UK; in 2002,18% of deaths in the USA were from heart disease, compared with 20% in the UK. The USA lost8 DALYs per 1000 population to heart disease and a further 4 DALYs per 1000 population to stroke,and the UK lost 7 DALYs per 1000 population to heart disease and 4 DALYs per 1000 populationto stroke. Afghanistan has the highest rate of DALYs lost to heart disease (36 DALYs per 1000population), and France, Andorra, Monaco, Japan, Korea, Dominica, and Kiribati have the lowest(1–3 DALYs per 1000 population). Mongolia has the highest rate for stroke (25 DALYs per 1000population lost) and Switzerland the lowest (2 DALYs per 1000 population lost).

AETIOLOGY/RISK FACTORS

Deaths from CHD are not evenly distributed across the population.They are more common in menthan in women; 67% more common in men from Scotland and the north of England than the southof England; 58% more common in male manual workers; twice as common in female manualworkers than female non-manual workers; and about 50% higher in South Asian people living inthe UK than in the average UK population. In the UK there are 14% more CHD deaths in the wintermonths than in the rest of the year. [1] CVD in the UK generally results from the slow build-up ofatherosclerosis over many decades, with or without thrombosis. The long development time ofatherosclerosis means that small changes in lifestyle may have profound effects on risk of CVDover decades. However, while there is strong evidence from epidemiological studies of the impor-tance of lifestyle factors — such as smoking, physical activity, and diet — in the process of devel-opment of CVD, [2] adjusting for confounding can be difficult, and the long timescales involvedmake proving the effectiveness of preventive interventions in trials difficult. In practice, risk fac-tors — rather than disease outcomes — are often the only practical outcomes for intervention

© BMJ Publishing Group Ltd 2007. All rights reserved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Primary prevention of CVD: diet and weight lossB

loo

d an

d lym

ph

diso

rders

studies in low-risk people. Such risk factors include blood pressure, body mass index, serum lipids,and development of diabetes.

PROGNOSIS Improvements in diet and reduction in weight may lower the risk of cardiovascular disease by ex-erting favourable changes on CVD risk factors (obesity, high blood pressure, elevated serum lipids,diabetes).

AIMS OFINTERVENTION

To change lifestyle factors, cardiovascular risk factors, and risk of CVD and death in the generalpopulation (adults without existing serious risk factors such as hypertension, dyslipidaemia, or dia-betes), with minimum adverse effects.

OUTCOMES Lifestyle change; changes in risk factors such as serum lipids, weight, blood pressure, and glucosetolerance; cardiovascular events such as myocardial infarction, angina, stroke, and heart failure;deaths (total or from CVD); adverse effects.

METHODS BMJ Clinical Evidence search and appraisal August 2006. The following databases were used toidentify studies for this review: Medline 1966 to August 2006, Embase 1980 to August 2006, andThe Cochrane Database of Systematic Reviews and Cochrane Central Register of ControlledClinical Trials 2006, Issue 3. Additional searches were carried out using these websites: NHSCentre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects(DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), andNational Institute for Health and Clinical Excellence (NICE). Abstracts of the studies retrieved wereassessed independently by two information specialists using pre-determined criteria to identifyrelevant studies. Study design criteria for inclusion in this review were: published systematic reviewsand RCTs in any language containing more than 20 individuals of whom more than 90% were fol-lowed up for a minimum of 12 months. We included open studies. In addition, we use a regularsurveillance protocol to capture harms alerts from organisations such as the US Food and DrugAdministration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA),which are added to the reviews as required.

QUESTION What are the effects of interventions in the general population to reduce sodium intake?

OPTION ADVICE TO REDUCE SODIUM INTAKE: EFFECTS ON CVD RISK. . . . . . . . . . . . . . . . . . . New

Two systematic reviews found that reducing sodium intake in people without hypertension reduced bloodpressure compared with usual diet. One subsequent RCT of very tight control of dietary sodium in peoplewith hypertension found that reducing sodium intake (as part of a low-fat and high-fruit-and-vegetable diet)reduced blood pressure.

Benefits: We found two systematic reviews [3] [4] and one subsequent RCT. [5]

Low-sodium diet for blood pressure:The first systematic review (search date not reported, 3 RCTs, 2326 adults without hypertension)found that dietary advice to people without hypertension to reduce their sodium intake comparedwith continuing on their usual diet significantly reduced mean systolic and diastolic blood pressureat 6–12 months (mean fall in systolic blood pressure: 2.3 mm Hg, 95% CI 1.6 mm Hg to 3.1 mm Hg;mean fall in diastolic blood pressure: 1.2 mm Hg, 95% CI 0.6 mm Hg to 1.8 mm Hg). [3] At 13–60months, effects of low-sodium dietary advice compared with usual diet were smaller (mean fall insystolic blood pressure: 1.1 mm Hg, 95% CI 0.3 mm Hg to 1.9 mm Hg; mean fall in diastolic bloodpressure: 0.5 mm Hg, 95% CI 0 mm Hg to 1.1 mm Hg). The advice was intensive, more than isusual in primary care.The second systematic review (search date 1996, 29 RCTs, 2 of which werein the first review, number of people not reported) compared less-intensive advice to reduce sodiumin people with normal blood pressure at baseline versus no restriction on the length of follow uprequired. [4] The review did not perform a meta-analysis, but it reported that a reduction in sodiumintake of 100 mmol daily (a reduction of about 60%) would result in reductions of about 1.0 mm Hgsystolic and 0.1 mm Hg diastolic blood pressure. We found one subsequent RCT (412 adults fromthe USA with systolic blood pressure of 120–159 mm Hg and diastolic blood pressure of80–95 mm Hg at baseline, 41% had hypertension [140–159 mm Hg systolic or 90–95 mm Hg av-erage in 3 screening visits], mean age 48 years, 56% women, 56% black, 40% non-Hispanic white).[5] This RCT is reported here despite its short length of follow up and high number of people withhypertension as it is unique in providing very tight control of dietary sodium and other constituentsby providing all food consumed for three 1-month periods, and therefore gives good estimates ofactual blood pressure response to specific changes in sodium intake. The RCT compared a dietrich in fruit, vegetables, and low-fat dairy foods and low in saturated and trans fats (the DASH diet[Dietary Approaches to Stop Hypertension]) versus a typical US diet.Within each diet, both groups

© BMJ Publishing Group Ltd 2007. All rights reserved. ........................................................... 3


loo

d an

d lym

ph

diso

rders

had 1 month periods of either high sodium (142 mmol sodium/day, which is close to the UK dailymean of 187 mmol in men and 139 mmol in women [6] ), intermediate (106 mmol/day), or low(65 mmol/day) sodium. For people without hypertension, those on the US diet had significant de-creases in systolic and diastolic blood pressure when moving from high to intermediate and fromintermediate to low sodium intakes and those on the DASH diet had smaller decreases in systolicand diastolic blood pressure when moving from high to intermediate or from intermediate to lowsodium intakes (see table 1, p 15 ). Additionally, being on a DASH diet resulted in consistentlylower blood pressure than being on the standard US diet; a dietary change to a diet high in fruit,vegetables, and low-fat dairy foods, low in saturated fat resulted in almost the same reduction inblood pressure as major salt reduction, but was likely to confer additional health benefits (e.g. onlipid levels). People on the low-sodium DASH diet had the lowest systolic blood pressure of all.

Low-sodium diet for cardiovascular disease and mortality:One systematic review compared the effect of dietary sodium advice versus usual diet on deathsand cardiovascular events. [3] It reported that there were too few events to draw any conclusions.

Harms: Low-sodium diet for blood pressure:The first review reported no adverse effects associated with advice to reduce sodium intake. [3]

The second review [4] and subsequent RCT [5] gave no information on harms.

Low-sodium diet for cardiovascular disease and mortality:The review reported no adverse effects associated with advice to reduce sodium intake. [3]

Comment: None.

OPTION ADVICE TO REDUCE SODIUM INTAKE: EFFECTS ON SODIUM INTAKE. . . . . . . . . . . . . New

One systematic review found that intensive advice to reduce sodium intake decreased sodium intake (mea-sured by sodium excretion) compared with usual diet.

Benefits: Effect on behaviour:We found one systematic review (search date 2000, 3 RCTs, 2326 adults without hypertension).[3] The review found that advice to reduce sodium intake significantly reduced excreted sodiumcompared with usual diet at 13–60 months (WMD –34 mmol sodium/24 hours, 95% CI –19 mmol/24hours to –50 mmol/24 hours).These RCTs were in healthy people, predominantly white, male, andfrom the USA, mean age 40 years, with blood pressure just below the definition of hypertension(mean diastolic blood pressure: 83–86 mm Hg; systolic blood pressure: 124–127 mm Hg). Theadvice in these three RCTs was intensive, and involved regular group and individual counsellingfor extended periods, as well as additional support materials such as recipes, lists of sodium contentsof common food brands, shopping expeditions, etc.

Harms: The review reported no adverse effects associated with advice to reduce sodium intake. [3]

Comment: Trials of dietary advice to reduce sodium in adults without hypertension found that those in the low-sodium arm had difficulties with their diets — including the diets being inconvenient, conflictingwith schedules, needing extra time to plan, and being difficult to stick to when eating out. However,in one trial, psychological wellbeing scores increased in those on the low-sodium diet comparedwith those on their usual diets. [3]

Clinical guide:This type of intensive intervention is not realistic in primary care, but we found no systematic reviewor RCTs assessing the effect of public health interventions such as reducing the sodium contentof processed foods, although this would seem a sensible way of making it easier for the wholepopulation to consume less sodium. Under highly controlled conditions, halving dietary sodium hassimilar effects in reducing blood pressure as a diet high in fruit, vegetables, low-fat dairy foods,wholegrain products, nuts, fish, and poultry, and low in saturated fat and sugars, compared with ausual US diet — and the fruit-and-vegetable diet would be expected to have additional beneficialeffects on lipids and other risk markers. There is evidence that a reduction of 20 mm Hg in systolicblood pressure is associated with halving of the risk of vascular mortality, so a reduction of 1 mm Hgsystolic resulting from intensive dietary interventions to reduce sodium intake in the studies abovewould be associated with a reduction in risk of about 2.5%. [7] This type of reduction is clinicallyimportant in a population but not in individuals. As the intensive intervention provided in the trialsis relevant to individuals, but not to populations, the results are clinically disappointing. The moreMediterranean-pattern diet is likely to have similar-sized effects through its blood pressure-loweringeffects, as well as additional benefits in promotion of healthy lipids, body weight, prevention of os-teoporosis, provision of additional fruit and vegetables, etc, and so may have a greater effect onprevention of cardiovascular disease and other chronic diseases.



loo

d an

d lym

ph

diso

rders

QUESTION What are the effects of a cholesterol-lowering diet in the general population?

OPTION ADVICE TO REDUCE SATURATED FAT INTAKE: EFFECTS ON CARDIOVASCULAR DISEASERISK. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . New

One systematic review found no significant difference in mortality between reducing dietary saturated fatintake compared with usual care at less than 2 years; however, it did find that reducing dietary saturated fatintake decreased mortality at 2 years or longer. A second systematic review found no significant differencein mortality between multiple interventions including reducing dietary saturated fat intake compared withusual care; however, the people in the RCTs were young, and follow-up was sometimes short.

Benefits: Effect on cardiovascular disease and mortality:We found two systematic reviews. [8] [9] The first systematic review (search date 1999, 27 RCTs,18,196 adults with and without cardiovascular disease [CVD], 14 RCTs of people with low CVDrisk, 6 RCTs of moderate risk, and 7 RCTs of high risk) compared low saturated fat advice or dietarysupport versus usual diet for at least 6 months. [8] The review found no significant difference intotal mortality or cardiovascular mortality between advice to reduce dietary fat compared withusual diet (total mortality: RR 0.98, 95% CI 0.86 to 1.12; cardiovascular mortality: RR 0.84, 95%CI 0.77 to 1.07). However, the review found that there were significantly fewer cardiovascularevents with advice to reduce dietary fat (RR 0.84, 95% CI 0.72 to 0.99). The review found no sig-nificant difference in cardiovascular events at 2 years or less between low saturated fat advice ordietary support compared with usual diet, but found that cardiovascular events were significantlyfewer at 2 years or more with advice to reduce fat (2 years or less: RR 0.96, 95% CI 0.75 to 1.23;2 years or more: RR 0.76, 95% CI 0.65 to 0.90). Subgroup analysis by level of cardiovascular risk(low risk: general population; medium risk: those with risk factors; high risk: those with existingCVD) and type of support (dietary advice, dietary advice plus supplements, or diet provided) seemedto make little difference to the effect size, although those at high risk showed a significant effectas there were more events in this group (cardiovascular events for those at low cardiovascularrisk: RR 0.82, 95% CI 0.56 to 1.20; high cardiovascular risk: RR 0.84, 95% CI 0.70 to 0.99). Thesecond systematic review (search date 1995, 14 RCTs with 6 months' follow-up or longer, 1,206,000person-years of observation in RCTs with risk-factor or clinical-event outcomes, and excludingthose in secondary prevention, or in children or adults under 40 years of age) compared multiple-risk-factor interventions versus no intervention. [9] The review found no significant difference inreduction in total or coronary heart disease mortality between multiple-risk-factor interventions andno intervention (total mortality: OR 0.97, 95% CI 0.92 to 1.02; coronary heart disease mortality:OR 0.96, 95% CI 0.88 to 1.04) over 903,000 person-years of observation, but the people weregenerally young (mean age 45.2–54.1 years) and follow-up was sometimes of short duration (meanfollow up 1.5–11.8 years).

Harms: The reviews gave no information on adverse effects. [8] [9]

Comment: None.

OPTION ADVICE TO REDUCE SATURATED FAT INTAKE: EFFECTS ON FAT INTAKE. . . . . . . . . . New

One systematic review found that multiple advice components to reduce saturated fat intake were associatedwith more reduction in saturated fat intake compared with simple dietary advice. A second systematic reviewfound inconclusive evidence on the effects of advice to reduce saturated fat intake compared with no advice.Four subsequent RCTs found that advice to reduce saturated fat intake was associated with reduced satu-rated fat intake.

Benefits: We found two systematic reviews [10] [11] and four subsequent RCTs. [12] [13] [14] [15] The firstsystematic review (search date 2001, 17 RCTs, more than 27,795 adults with and without riskfactors for cardiovascular disease [CVD]) compared dietary advice to reduce total or saturated fatintake for at least 3 months versus usual diet. [10] Of the 17 RCTs assessing the effect of dietarycounselling on saturated fat intake, six RCTs found a self-reported large effect size in people's re-duction in saturated fat intake (as either grams of saturated fat or percentage of calories as satu-rated fat) (a reduction of more than 3%), five RCTs found a medium effect (1.3–3.0% reduction),and six RCTs found a small effect (less than 1.3% reduction). Effect sizes were calculated using(in order of preference): net difference in change, difference at final follow-up, or relative change.In this analysis, RCTs that used more intensive interventions achieved greater effect sizes. Thosein primary care settings tended to produce small- or medium-sized effects, mainly because theyused lower-intensity interventions than those in special research clinics. Using more components(dietary assessment, family involvement, social support, group counselling, food interaction suchas taste testing and cooking, goal setting, and advice appropriate to the patient group) was asso-ciated with greater effect sizes. The authors of the review reported that baseline level of CVD risk



loo

d an

d lym

ph

diso

rders

did not seem associated with effect size after stratification for intensity of intervention. The secondsystematic review (search date 1993) identified eight RCTs, 3 of which were also identified by thefirst review [10] , assessing diets to reduce dietary fat in primary prevention of free-living adults overat least 3 months. [11] It reported that, at 9–18 months, only four RCTs noted effects in reporteddietary fat intake, two of which were trials of breast cancer prevention. The review did not performa meta-analysis because of heterogeneity between RCTs. Two RCTs found a significant reductionin dietary fat intake with advice compared with no advice — however, these were the two trials ofbreast cancer prevention. RCTs included in the review that reported both dietary saturated fat intakeand blood lipids suggested significant effects on dietary fat, but non-significant effects onlipids — suggesting that self-reported saturated fat intake may not be a good indicator of usual intake.[11] The first subsequent RCT (235 healthy people aged 30–59 years with siblings who were diag-nosed with coronary heart disease before the age of 60 years) found that nurse counselling signif-icantly reduced saturated fat intake at 2 years compared with usual care (–4.9 g/day with counsellingv +1.9 g/day with usual care; P = 0.0002). [12] The second subsequent RCT (545 premenopausalwomen, mean age 47 years) found that a 5-year cognitive behavioural programme significantlyreduced saturated fat as a percentage of total calories compared with no programme (9% withprogramme v 11% with no programme; P less than 0.05). [13] The third subsequent RCT (616healthy women aged 40–70 years) found a significant reduction in total fat as a percentage of en-ergy in the intervention group compared with control (advice for breast self-examination) at 12months (35% with counselling v 39% with control; P less than 0.001). [14] The fourth subsequentRCT (143 people with an “elevated” risk for CVD, mean age 58 years) also found a significant re-duction in energy from saturated fat 12 months after nutritional counselling by family physicianscompared with no advice (–3% with counselling v –1% with no advice; P less than 0.05). [15]

Harms: The systematic reviews [10] [11] and RCTs [12] [13] [14] [15] gave no information on adverse effects.

Comment: Once people in a trial have been told to reduce total or saturated fat, they have a tendency to un-derreport their intake to a greater extent than control groups. There is often inconsistency in effec-tiveness when trials report both changes in fat intake (which is self reported in a variety of ways)and serum lipids (which are likely to provide a better view of saturated fat intake over the past fewweeks). Trials often report significant reductions in dietary fats without significant changes in totalor low-density lipoprotein cholesterol.

QUESTION What are the effects of interventions to increase or maintain weight loss?

OPTION DIETS AND BEHAVIOURAL INTERVENTIONS: EFFECTS ON WEIGHT LOSS. . . . . . . . . New

Systematic reviews and RCTs found that combinations of interventions (physical, dietary, and behavioural)reduced body weight compared with usual care. Systematic reviews and RCTs of less complex interventionsfound that they were less effective at reducing body weight.

Benefits: Weight-reducing diets, effect on weight:We found two systematic reviews [16] [17] and one subsequent RCT. [18] The first systematic review(search date 2001, 26 RCTs, 3048 people with body mass index [BMI] of 28 kg/m2 or greater) in-cluded RCTs that compared weight-reducing diets versus usual diets, where weight was measuredafter at least 12 months. [16] Thirteen RCTs of low-fat diets compared with usual diet found thatlow-fat diets resulted in greater weight loss at 12 months (WMD –5.3 kg, 95% CI –5.9 kg to –4.8 kg),24 months (WMD –2.4 kg, 95% CI –3.6 kg to –1.2 kg), and 36 months (WMD –3.6 kg, 95% CI–4.5 kg to –2.6 kg), with no significant difference at 60 months (WMD –0.2 kg, 95% CI –2.0 kg to+1.6 kg). [16] Comparisons of low-calorie or very-low-calorie diets versus usual diet were only foundin subgroups of people with chronic illness. RCTs comparing low-calorie diets versus low-fat diets,very-low-calorie diets versus low-fat diets, and very-low-calorie diets versus low-calorie diets werefound, but studies were small and no significant differences were found at 12 months or later. [16]

The second systematic review (search date 2003, 29 RCTs) included systematic reviews and RCTsof screening for obesity, weight-reducing, and weight-maintaining interventions. [17] The reviewfound that weight loss trials most likely to succeed were high intensity (where contact was morefrequent than monthly).The subsequent RCT (160 people) compared four weight-loss diets (Atkins,Zone, Weight Watchers, and Ornish diets) and found no significant differences in weight loss at 1year or study completion (at 1 year: –2.1 kg with Atkins v –3.2 kg with Zone v –3.0 kg with WeightWatchers v –3.3 kg with Ornish; P = 0.4 between groups; at study completion: –52% with Atkinsv –65% with Zone v –65% with Weight Watchers v –50% with Ornish; P = 0.08 between groups).[18]

Behavioural interventions, effect on weight:We found one systematic review (search date 2003, 36 RCTs, 3495 overweight or obese people,BMI greater than 25 kg/m2 ) of psychological interventions for sustained weight loss in overweight



loo

d an

d lym

ph

diso

rders

or obese adults. [19] Ten of these RCTs compared a behavioural intervention versus no treatment,and two reported outcomes later than 12 months, finding that those in the behavioural-interventionarm lost more weight on average than those in the control arm (–2.0 kg, 95% CI –2.7 kg to –1.3 kg).Comparing more-intensive versus less-intensive behavioural interventions (10 RCTs, 306 people)found significantly greater weight loss in those on more-intensive interventions in studies of up to1 year (–2.3 kg, 95% CI –3.3 kg to –1.4 kg). One RCT assessed outcomes longer than 1 year andfound no significant difference in weight loss. [19] Cognitive behavioural therapy (CBT) added todiet plus exercise versus diet plus exercise alone (2 RCTs, 63 people) showed significantly moreweight loss with CBT (–4.9 kg, 95% CI –7.3 kg to –2.4 kg). Direct comparison of CBT comparedwith behavioural interventions found that CBT was associated with significantly more weight loss(1 RCT, 24 people, difference of 5.7 kg; P less than 0.01). [19] We found a second systematic reviewasking whether brief interventions using motivational interviewing were effective across severalbehavioural domains including diet and exercise (search date 1999, 29 RCTs of which 5 were ofdiet plus exercise), and which included RCTs that compared motivational interviewing versus acontrol group. [20] Using unit-free effect sizes, they suggest that three of the five trials showedstatistically significant benefit. One additional RCT of 92 overweight adults (mean BMI 33.1 kg/m2

) compared behavioural counselling plus internet-based weight-loss programme versus internet-based weight-loss programme alone, and found greater weight loss in the behavioural counsellinggroup at 12 months (–4.4 kg with behavioural counselling plus internet-based weight-loss programmev –2.0 kg with internet-based weight-loss programme alone; P = 0.04). [21]

Combined interventions, effect on weight:We found one systematic review (search date 2003), which suggested that successful interventionswere more likely to include two or three strategies (combining behavioural, dietary, and physicalactivity intervention). [17] One large RCT identified by the review (1191 men and women) comparingweight loss using dietary, physical, and social support versus usual care found that combined in-terventions reduced weight by 2.7 kg at 18 months and 2.0 kg at 36 months (no further data report-ed). [22] We also found three subsequent RCTs. [23] [24] [25] The first subsequent RCT (423overweight and obese adults) identified by the review compared the effect of participation in theWeight Watchers commercial programme of group-based dietary, physical activity, and behaviouralchange with two 20-minute nutritionist interviews and self-help materials. It found that those ran-domised to the commercial programme had lost more weight at 2 years (–2.7 kg; P less than 0.001),and had greater decreases in waist circumference and BMI. [23] The second subsequent RCT (44obese sedentary postmenopausal women) added self-control skills training to a comprehensiveprogramme of lifestyle, exercise, attitudes, relationships, and nutrition. [24] The RCT found thatself-control skills plus comprehensive programme significantly reduced weight compared withcomprehensive programme (–6.5%; no further data reported). The third subsequent RCT (110obese men with erectile dysfunction) found that detailed advice on diet and physical activity (com-pared with general advice to the control group) resulted in significant reductions in BMI in the inter-vention compared with the control group, after 2 years (no further data reported). [25]

Physical activity plus weight-reducing diets versus weight-reducing diets alone, effect onweight:One systematic review compared weight-reducing diets plus exercise versus weight-reducing dietsalone in adults with obesity (search date 2001). [26] The review found that adding exercise to dietsignificantly increased mean weight loss (at 12 months: –1.95 kg, 95% CI –3.22 kg to –0.68 kg; at36 months: –8.22 kg, 95% CI –15.27 kg to –1.16 kg).

Behavioural therapy plus weight-reducing diets with or without physical activity versusweight-reducing diets with or without physical activity, effect on weight:One systematic review found that adding behavioural therapy to weight-reducing diet significantlyimproved weight loss at 12 months, but found no significant difference at later time points (4 RCTs;at 12 months: –7.7 kg, 95% CI –12.0 kg to –3.4 kg; at 36 months: +2.9 kg, 95% CI –2.8 kg to+8.6 kg; at 60 months: –1.9 kg, 95% CI –7.6 kg to +3.8 kg). [26] However, in one cluster RCT, ad-dition of behavioural therapy to weight-reducing diets plus exercise did not improve weight loss at12 months compared with weight-reducing diets plus exercise, and addition of exercise and be-havioural therapy to diet did not significantly improve weight loss at 12 months. A second system-atic review found that adding behavioural therapy to diet plus exercise (compared with diet plusexercise alone) produced a heterogeneous result, but that five of the six studies favoured the additionof behavioural therapy (the sixth favoured diet plus exercise alone). [19]

Harms: Adverse effects were addressed in few reviews or trials. One review found that adverse effects(such as illnesses and deaths) occurred in both arms, but, as such events were rare, patterns werenot clear. [26] One subsequent RCT reported that it did not identify any serious adverse effects ofthe diets. [18]



loo

d an

d lym

ph

diso

rders

Comment: The main methodological issue in weight-reducing trials is the high level of withdrawals, particularlyin the longer trials, which can provide more useful information. People who completed trials tendedto do better, and differential withdrawal rates can misrepresent the effectiveness of interventions.Potential adverse effects that should be assessed in trials and reviews include eating disorderssuch as anorexia or bulimia (which might be precipitated by a concentration on body image, food,and exercise) and rebound binge eating (which might lead to increased weight, but would tend tooccur in those who have withdrawn from the study).

OPTION LIFESTYLE INTERVENTIONS: EFFECTS ON MAINTAINANCE OF WEIGHT LOSS. . . . . New

One systematic review found that weight-maintenance strategies can maintain weight loss; however, thereview reported few details of how the conclusion was reached. RCTs found inconclusive evidence on theeffects of different lifestyle interventions (physical, dietary, and behavioural) to maintain weight loss.

Benefits: Effects on weight:We found one systematic review (search date 2003, 29 RCTs, included systematic reviews andRCTs of screening for obesity, weight-reducing and weight-maintaining interventions). [17] It foundthat maintenance strategies helped to maintain weight loss (mentioning 2 trials) but provided fewdetails of how this conclusion was reached.We found six RCTs of weight-maintenance programmesof at least 1 year after a weight-loss programme. [27] [28] [29] [30] [31] [32] The first RCT (82 obesemen, mean body mass index [BMI] 32.9 kg/m2, mean weight 106.0 kg, who had a very-low-energydiet for 2 months, mean body weight after the diet 91.7 kg) found no significant difference in meanbody weight at 31 months between walking (45 minutes 3 times weekly for 6 months), resistancetraining (45 minutes 3 times weekly for 6 months), and no exercise (102.0 kg with walking v 99.9 kgwith resistance training v 100.7 kg with no exercise; P = 0.8 between groups). [27] The second RCT(82 obese premenopausal women, mean BMI 34.0 kg/m2, mean weight 92.0 kg, who had a very-low-energy diet for 3 months, mean weight loss after the diet 13.1 kg) found no significant differencein mean body weight between diet counselling plus a walking programme (to expend 4.2 MJ/week),diet counselling plus a more intensive walking programme (to expend 8.4 MJ/week), and dietcounselling alone (83.9 kg with lower walking programme v 87.4 kg with higher walking programmev 89.7 kg with no walking; P = 0.07 between groups). [28] The third RCT (80 obese women whosemean weight loss was 8.74 kg in an initial 20-week behavioural treatment programme, who thenhad either: problem-solving therapy, relapse prevention training, or no further treatment for 12months) found that women who had subsequent problem-solving therapy lost significantly morebody weight than women who had no further treatment (10.8 kg with problem-solving therapy v4.1 kg with no treatment; P = 0.019). [29] The RCT found no significant difference between anyother comparison (P values not reported). The fourth RCT (128 African-American people, meanBMI 37.5 kg/m2 who had a 10-week healthy eating and lifestyle programme, mean weight loss1.5 kg, mean BMI after the programme 37.0 kg/m2 ) found no significant difference at 8–20 monthsin change of body weight from baseline between people who had either further group counselling,staff-facilitated self help, or clinic visits only (–0.8 kg with group counselling v –1.3 kg with self helpv –1.4 kg with clinic visits; P = 0.90 between treatments). [30] The fifth RCT (255 people, mean BMI31.8 kg/m2, mean body weight 89.4 kg, who had a 6-month weight control programme by interactivetelevision, mean weight loss 7.8 kg) found no significant difference in overall weight loss at the endof a 12-month maintenance period between three maintenance strategies: frequent therapist contact,minimum therapist contact, and internet therapist support (5.1 kg with frequent therapist contact v5.5 kg with minimum therapist contact v 7.6 kg with internet therapist support; P = 0.23). [31] Thesixth RCT (67 people who had a 6-month weight-loss programme, mean weight loss 8.8 kg, meanBMI after the programme 30.8 kg/m2, mean body weight 85.2 kg, mean weight and BMI beforeprogramme not reported) found that people completing a weight-focused maintenance programmegained significantly less weight pver 12 months than people on an exercise-focused maintenanceprogramme (+0.8 kg with weight-focused maintenance programme v +4.4 kg with exercise-focusedmaintenance programme; P less than 0.01). [32]

Harms: The systematic review [17] and subsequent RCTs [27] [28] [29] [30] [31] [32] gave no informationon adverse effects.

Comment: None.

OPTION LIFESTYLE INTERVENTIONS: EFFECTS ON PREVENTING WEIGHT GAIN. . . . . . . . . . New

One systematic review and two RCTs found inconclusive evidence on the effects of lifestyle interventionsto prevent weight gain.



loo

d an

d lym

ph

diso

rders

Benefits: Effects on weight:We found one systematic review, [33] one additional RCT, [34] and one subsequent RCT. [35] Thesystematic review (search date not reported, 5 studies [4 controlled and 1 uncontrolled], numberof people not reported) assessed community interventions promoting physical activity for preventingweight gain. [33] It found no significant effects of the intervention on weight gain. The additionalRCT compared education (by newsletters) versus education plus incentives versus no educationto prevent weight gain. [34] It found no significant difference in a between-group comparison inweight gain at 3 years (+1.6 kg with education v +1.5 kg with education plus incentives v +1.8 kgwith no education; P = 0.80). The subsequent RCT compared a dietary and physical advice pro-gramme with no programme (assessment only) (535 premenopausal women, aged 44–50 years).[35] It found that weight gain was significantly greater with the advice programme than with noprogramme (–0.1 kg with advice v +2.4 kg with no advice; reported as significant; P value not re-ported). It also found that body mass index increase was significantly less with the advice programmethan with no programme (+0.05 kg/m2 with advice v +0.96 kg/m2 with no advice; P less than 0.001).

Harms: The review [33] and additional RCT [34] gave no information on adverse effects. The subsequentRCT found no signs of increased stress, depressive symptoms, or eating restraint among peoplein the intervention group. [35]

Comment: None.

OPTION TRAINING HEALTH PROFESSIONALS IN PROMOTING WEIGHT LOSS: EFFECTS ON WEIGHTLOSS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . New

One systematic review and one subsequent RCT found inconclusive evidence on the effects of traininghealth professionals for promoting weight loss.

Benefits: Organisational and educational interventions with healthcare staff, effect on weight (of pa-tients):We found one systematic review [36] and two subsequent RCTs. [37] [38] The systematic review(search date 2000; 5 RCTs, 1 controlled before and after study, 2992 overweight or obese people)compared interventions to improve health professionals' management of weight versus no interven-tions. [36] It did not perform a meta-analysis, as some of the studies were small and of low quality;however, the review authors suggested that reminder systems, brief training interventions, sharedcare, inpatient care, and dietician-led treatments may be effective in improving management ofweight.The first subsequent RCT cluster compared obesity management training versus no trainingin 44 general practices. [37] The RCT found no significant difference in weight change in obesepeople in the practices with training than with no training at 12 months (843 obese people; +1 kg,95% CI –1.9 kg to +3.9 kg; P = 0.5). The second subsequent RCT compared dietician counselling,dietician counselling plus doctor counselling, and no counselling. [38] It found that dietician coun-selling resulted in significantly more weight loss than no counselling (–6.6%, 95% CI –7.6% to–5.8%), and that dietician plus doctor counselling resulted in significantly more weight loss thanno counselling (–7.3%, 95% CI –8.3% to –6.5%).There was no significant difference in weight lossbetween doctor plus dietician counselling and dietician only counselling (+0.7%, 95% CI –0.42%to +1.82%).

Harms: The review [36] and RCTs [37] [38] gave no information on adverse effects.

Comment: None.

OPTION DIETS AND BEHAVIOURAL INTERVENTIONS: EFFECTS ON CVD RISK. . . . . . . . . . . . . New

We found no systematic review or RCTs assessing the effects of diets and behavioural intervention in reducingcardiovascular risk in the general population.

Benefits: Effects on cardiovascular risk:We found no systematic review or RCTs.

Harms: We found no RCTs.

Comment: None.



loo

d an

d lym

ph

diso

rders

QUESTION What are the effects on reducing CVD risk in the general population of eating more fruit andvegetables?

OPTION INCREASING FRUIT AND VEGETABLE INTAKE: EFFECTS ON CARDIOVASCULAR DISEASERISK. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . New

Two systematic reviews of cohort studies found that increasing fruit and vegetable intake decreased cardio-vascular risk.

Benefits: Effect on cardiovascular disease risk:We found no systematic review of RCTs but found two systematic reviews of cohort studies. [39]

[40] The first systematic review (search date 2002, 8 cohort studies assessing the effects of fruitand vegetable consumption on CVD, total number of people not reported) reported that seven ofthe eight cohort studies found that a higher intake of fruit and vegetables decreased CVD riskcompared with low intake — suggesting protection with higher intakes (no further data reported;results presented graphically). [39] The second systematic review (search date not reported, 11cohort studies on the effect of fruit and vegetable intake on deaths from ischaemic heart disease)found that most markers of fruit and vegetable intake (including dietary carotenoids, vitamin C, fruitfibre, and vegetable fibre) decreased ischaemic heart disease.Total fruit intake and total vegetableintake also decreased ischaemic heart disease, but less so.

Harms: The reviews gave no information on adverse effects. [39] [40]

Comment: One earlier systematic review (search date 1995, ecological, case control and cohort studies as-sessing the relationship between fruit and vegetable intake and CVD; number of people not reported)found that six of 16 cohort studies suggested a statistically significant effect. [41]

OPTION BEHAVIOURAL AND COUNSELLING INTERVENTIONS: EFFECTS ON FRUIT AND VEGETABLEINTAKE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . New

One systematic review found no significant difference in increase in fruit and vegetable intake between adviceto increase fruit and vegetable intake and usual diet. One subsequent RCT found inconclusive evidence oncounselling to increase fruit and vegetable intake. A second subsequent RCT found that computer-assistedintervention to increase fruit and vegetable intake in healthy women increased intake compared with acontrol of counselling on breast self-examination.

Benefits: We found two systematic reviews [10] [42] and one subsequent RCT [14] of dietary interventions toincrease the quantity of fruit and vegetables eaten. The first systematic review (search date notreported, included 12 controlled trials [unclear if they were RCTs], number of people not reported)assessed the effect of behavioural interventions to increase fruit and vegetable intake comparedwith control or usual diet. [42] It found no significant difference in the median “difference in deltas”of increase in quantity of fruit and vegetables eaten (+16.6, range –3.7 to +60.9). The secondsystematic review (search date 2001, 10 RCTs of counselling to increase fruit and vegetable intakecompared with no counselling; 1 of the RCTs was included in the first systematic review; [42]

number of people not recorded) found that three RCTs produced small or no increases in fruit andvegetables (less than 0.3 servings/day), five RCTs found medium increases (0.3–0.8 servings/day),and two RCTs found large effects (1.4–3.2 servings/day; no further data reported). [10] One subse-quent RCT (616 healthy women) found that a brief computer-assisted intervention to reduce dietaryfat and increase fruit and vegetable consumption compared with a control intervention (counsellingon breast self-examination) resulted in significantly higher self-reported intake of fruit and vegetableservings with computer intervention at 12 months compared with control intervention (4.33 serv-ings/day with computer intervention v 3.40 servings/day with control intervention; P less than 0.001).[14]

Harms: The systematic reviews [10] [42] and subsequent RCT [14] gave no information on harms.

Comment: None.

QUESTION What are the effects on reducing CVD risk of antioxidants in the general population?

OPTION HIGH-DOSE ANTIOXIDANT SUPPLEMENTS: EFFECTS ON CARDIOVASCULAR RISK. . New

Systematic reviews found that high-dose supplements of vitamin E and beta carotene did not reduce mor-tality or cardiovascular events.

© BMJ Publishing Group Ltd 2007. All rights reserved. .......................................................... 10


loo

d an

d lym

ph

diso

rders

Benefits: Vitamin E:We found four systematic reviews [43] [44] [45] [46] and one subsequent RCT [47] on the effects ofvitamin E on cardiovascular disease (CVD) and mortality. The first review (search date 2004, in-cluding 9 RCTs that tested vitamin E alone, and 10 that tested vitamin E in combination with othervitamins and minerals) compared vitamin E versus placebo or control in non-pregnant adults overat least 1 year. [43] This review aimed to assess any dose–response relationship between vitaminE supplementation and total mortality. Some studies included those with, or at high risk of, CVD,but most did not. The review found that, overall, there was no effect of vitamin E on total mortality(RR 1.01, 95% CI 0.98 to 1.04). Dose–response analysis suggested that all-cause mortality in-creased with dose, and high-dose vitamin E (400 IU/day or more) significantly increased deaths(risk difference: 39/10,000 people, 95% CI 3/10,000 people to 74/10,000 people). However, RCTsusing high doses tended to be small and to include people with chronic disease.The second review(search date 2002, 84 RCTs of vitamin E on CVD, risk factors, or death) found no evidence torecommend vitamin E alone or in combination for the primary prevention of CVD). [44] The primaryprevention RCTs were not pooled. One of two primary prevention RCTs showed a significant re-duction in total mortality in a trial of vitamin E plus beta carotene plus selenium in rural China(mainly owing to reductions in cancer mortality). Neither (of two) primary prevention trials of vitaminE with other vitamins showed any effect of vitamin E on total, fatal, or non-fatal myocardial infarction.There is a suggestion of statistically (but not clinically) significant reductions in total and low-densitylipoprotein cholesterol levels in those taking vitamin E in primary prevention studies, but units,confidence intervals, and P values were not reported.The third review (search date 2001, 8 RCTs,104 512 people) analysed the effects of vitamin E, beta carotene, and ascorbic acid for primaryprevention. [45] The review found no significant in CVD at 3–12 years difference between vitaminE compared with no antioxidant supplement (4 RCTs, 48 346 people: OR 0.96, 95% CI 0.88 to1.04). The fourth review (search date not reported, 7 RCTs, 106 615 people [including secondaryprevention]) found no significant difference in cardiovascular events between high-dose vitamin E(30–800 mg/day) compared with no vitamin E (any event: OR 0.98, 95% CI 0.94 to 1.03; non-fatalmyocardial infarction: OR 1.00, 95% CI 0.92 to 1.09; non-fatal stroke: OR 1.03, 95% CI 0.93 to1.14; cardiovascular death: 1.00, 95% CI 0.94 to 1.05). [46] One subsequent RCT (39,876 healthywomen in the USA) compared vitamin E (600 IU on alternate days) versus placebo for 10 years.[47] The RCT found no significant difference in myocardial infarction, stroke, or total mortality betweenvitamin E compared with placebo (myocardial infarction: RR 1.01, 95% CI 0.82 to 1.23; stroke: RR0.98, 95% CI 0.82 to 1.17; total mortality: RR 1.04, 95% CI 0.93 to 1.16). However, the RCT didfind significantly fewer cardiovascular deaths with vitamin E compared with placebo (RR 0.76, 95%CI 0.59 to 0.98).

Beta carotene:One systematic review (search date 2001, 8 RCTs, 104,512 people) analysed the effects of vitaminE, beta carotene, and ascorbic acid for primary prevention. [45] The review found no significantdifference in CVD at 3–12 years between beta carotene and no antioxidant supplement (6 RCTs,85 056 people: OR 1.02, 95% CI 0.96 to 1.08). A second systematic review (search date not report-ed, 8 RCTs, 138,113 people with and without CVD) [48] found that beta carotene 15–50 mg dailysignificantly increased all-cause mortality at 1.4–12.0 years compared with placebo (OR 1.07, 95%CI 1.02 to 1.11). However, the data for both primary and secondary prevention RCTs were pooled,and no separate meta-analysis for primary prevention RCTs was reported.

Combination of antioxidants:One RCT compared a combination of antioxidants (ascorbic acid 120 mg plus vitamin E 30 mgplus beta carotene 6 mg plus selenium 100 ìg plus zinc 20 mg) versus placebo for 7.5 years. [49]

The RCT found no significant difference in CVD events or total mortality at 7.5 years (13,017 healthymiddle-aged people in France; CVD: RR 0.97, 95% CI 0.77 to 1.20; total mortality: RR 0.77, 95%CI 0.57 to 1.00). However, subgroup analysis by sex found significantly less mortality in men, butfound no significant difference in women (men: RR 0.63, 95% CI 0.42 to 0.93; women: RR 1.03,95% CI 0.64 to 1.63).

Harms: One review reported that there were “serious adverse cardiovascular effects” with vitamin E in oneRCT, and increased risk of intracerebral haemorrhage with beta carotene (data not reported). [45]

The review also reported that, in two RCTs, risk of lung cancer was increased with beta carotenein cigarette smokers. One subsequent RCT found significantly more epistaxis with vitamin E com-pared with placebo (RR 1.06, 95% CI 1.01 to 1.11). [47] Four systematic reviews [43] [44] [46] [48]

and one RCT [49] did not report on adverse effects.

Comment: None.



loo

d an

d lym

ph

diso

rders

QUESTION What are the effects on reduction of CVD risk of omega 3 fatty acids in the general popula-tion?

OPTION OMEGA 3 FATTY ACIDS: EFFECTS ON CARDIOVASCULAR RISK. . . . . . . . . . . . . . . . . New

One systematic review found no significant difference between omega 3 supplementation or advice to increaseomega 3 intake compared with placebo in mortality.

Benefits: We found one systematic review (search date 2002, 48 RCTs, 36 913 people), which comparedhigh-dose omega 3 supplementation or dietary advice for at least 6 months versus control orplacebo. [50] If found no significant difference in mortality between omega 3 supplements or advicecompared with placebo or no advice (44 RCTs, 36,195 people; RR 0.87, 95% CI 0.73 to 1.03; in-cluding 1 RCT of people at high and low risk of cardiovascular disease [CVD], and including RCTsof fish- and plant-based omega 3 fatty acids).There was also no significant difference for the samecomparison in people with a low risk of CVD (17 RCTs, 14,599 people; RR 1.07, 95% CI 0.70 to1.64). There was no significant difference for the same comparisons in RCTs with a low risk ofbias, but any risk of CVD (RR 0.98, 95% CI 0.70 to 1.36). There was no significant difference inmortality in subgroup analyses of RCTs of advice to eat more oily fish compared with no advice,or fish oil capsules compared with placebo (advice: RR 0.91, 95% CI 0.57 to 1.44; capsules: RR0.90, 95% CI 0.76 to 1.07).

Harms: We found no evidence of increase in cancers with increased omega 3 intake, but estimates wereimprecise and a clinically important effect could not be excluded. Trials reported fewer than 400cancers (mainly cancer deaths) overall and suggested no effect of omega 3 fatty acids on cancer(10 RCTs, cancer death or diagnoses: 391/17,433 [2%]; RR 1.07, 95% CI 0.88 to 1.30).The reviewof cohort studies found no increase in cancers in those taking greater quantities of omega 3 fattyacids (10 cohort studies, number of people not reported; RR 1.02, 95% CI 0.87 to 1.19). [50]

Comment: Clinical guide:Lack of protective effects of high doses of omega 3 fatty acids in the general public does not meanthat oily fish at more usual dietary levels are not healthy. General population advice in the UK isthat people should eat two portions of fish a week, one of which should be oily. [51] The UK Com-mittee on Toxicity, which reviewed the effects of oily fish and their contaminants with the ScientificAdvisory Committee on Nutrition, set safe upper limits for intake of oily fish on the basis of a widereview of the evidence. [51]

QUESTION What are the effects on reduction of CVD risk of a Mediterranean diet in the general popula-tion?

OPTION MEDITERRANEAN DIET: EFFECTS ON CARDIOVASCULAR RISK. . . . . . . . . . . . . . . . . New

We found insufficient evidence on the effects of Mediterranean diet on risk factors for cardiovascular disease,cardiovascular events, or deaths in the general population.

Benefits: We found no systematic review or RCTs on the effects of Mediterranean diet on risk factors forcardiovascular disease, cardiovascular events, or deaths in the general population. We found onesystematic review (search date not reported; 1 prospective cohort study, 22,034 “middle-aged andolder adults” in Greece). [52] It found that, with a 2/9 increment in Mediterranean diet score (notdescribed), there was a 25% reduction in total mortality and 33% reduction in heart disease mor-tality (after adjustment for sex, smoking, education, body mass index, or physical activity) in peopleover 55 years old only (no further data reported).

Harms: The non-systematic review gave no information on adverse effects. [52]

Comment: Clinical guide:The Mediterranean diet is a pattern of eating characterised by use of olive oil for cooking and littleuse of dairy fats. Other characteristics of this diet include increased intake of oily fish, fruit, vegeta-bles, nuts, pulses (and occasionally low-fat dairy products and red wine), and a lower intake ofprocessed foods, meat, meat products, and hard fats, compared with a typical European or USdiet.

GLOSSARYAtkins diet Strictly limits carbohydrate intake while allowing free intakes of protein and fat.Body mass index (BMI) Calculated by weight (in kilograms) divided by height (in metres) squared.



loo

d an

d lym

ph

diso

rders

Ornish diet Strict diet limiting cholesterol and saturated fat (prohibiting meat), sugars, and alcohol, while promotingcomplex carbohydrates. Aims at 10% of energy from fat, 20% from protein, and 70% from carbohydrates.Weight Watchers diet Group-based restriction of portion sizes and calories based on an exchange system.Zone diet Aims at 40% of energy from carbohydrates, 30% from protein, 30% from fat from all meals and snacks.

SUBSTANTIVE CHANGESNew option added Advice to reduce sodium intake: effects on CVD risk.New option added Advice to reduce sodium intake: effects on sodium intake.New option added Advice to reduce saturated fat intake: effects on cardiovascular disease risk.New option added Advice to reduce saturated fat intake: effects on fat intake.New option added Diets and behavioural interventions: effects on weight loss.New option added Lifestyle interventions: effects on maintainance of weight loss.New option added Lifestyle interventions: effects on preventing weight gain.New option added Training health professionals in promoting weight loss: effects on weight loss.New option added Diets and behavioural interventions: effects on CVD risk.New option added Increasing fruit and vegetable intake: effects on cardiovascular disease risk.New option added Behavioural and counselling interventions: effects on fruit and vegetable intake.New option added High-dose antioxidant supplements: effects on cardiovascular risk.New option added Omega 3 fatty acids: effects on cardiovascular risk.New option added Mediterranean diet: effects on cardiovascular risk.

REFERENCES1. British Heart Foundation. British Heart Foundation Statistics Website. Available

online at: http://www.heartstats.org/ (last accessed 17 July 2007).

2. World Health Organization. The atlas of heart disease and stroke. Geneva: TheWorld Health Organization, 2004. Available online at: http://www.who.int/cardio-vascular_diseases/resources/atlas/en/index.html (last accessed 17 July 2007).

3. Hooper L, Bartlett C, Davey Smith G, et al. Advice to reduce dietary salt for pre-vention of cardiovascular disease. In: The Cochrane Library, Issue 3, 2006.Chichester, UK: John Wiley & Sons, Ltd. Search date 2000.

4. Fodor JG, Whitmore B, Leenen F, et al. Lifestyle modifications to prevent andcontrol hypertension. 5. Recommendations on dietary salt. Canadian HypertensionSociety, Canadian Coalition for High Blood Pressure Prevention and Control,Laboratory Centre for Disease Control at Health Canada, Heart and StrokeFoundation of Canada. CMAJ 1999;160:S29–S34. Search date 1996.[PubMed]

5. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduceddietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet.New Engl J Med 2001;344:3–10.[PubMed]

6. Henderson L, Irving K, Gregory J, et al. The National Diet and Nutrition Survey:adults aged 19 to 64 years. Vitamin and mineral intake and urinary analysis.Newport: HMSO, 2003.

7. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual bloodpressure to vascular mortality: a meta-analysis of individual data for one millionadults in 61 prospective studies. Lancet 2002;360:1903–1913. [PubMed]

8. Hooper L, Summerbell CD, Higgins JP, et al. Reduced or modified dietary fat forprevention of cardiovascular disease. In: The Cochrane Library, Issue 3, 2006.Chichester, UK: John Wiley & Sons, Ltd. Search date 1999.

9. Ebrahim S, Smith GD. Systematic review of randomised controlled trials of mul-tiple risk factor interventions for preventing coronary heart disease. BMJ1997;314:1666–1674.[PubMed]

10. Pignone MP, Ammerman A, Fernandez L, et al. Counseling to promote a healthydiet in adults: a summary of the evidence for the U.S. Preventive Services TaskForce. Am J Prev Med 2003;24:75–92. [PubMed]

11. Brunner E, White I, Thorogood M, et al. Can dietary interventions change dietand cardiovascular risk factors? A meta-analysis of randomized controlled trials.Am J Public Health 1997;87:1415–1422. Search date 1993.[PubMed]

12. Moy TF, Yanek LR, Raqueno JV, et al. Dietary counseling for high bloodcholesterol in families at risk of coronary disease. Prev Cardiol2001;4:158–164.[PubMed]

13. Kuller LH, Simkin-Silverman LR, Wing RR, et al. Women's Healthy LifestyleProject. A randomized clinical trial: results at 54 months. Circulation2001;103:32–37.[PubMed]

14. Stevens VJ, Glasgow RE, Toobert DJ, et al. One-year results from a brief, com-puter-assisted intervention to decrease consumption of fat and increase consump-tion of fruits and vegetables. Prev Med 2003;36:594–600.[PubMed]

15. van der Veen J, Bakx C, Van den Hoogen HV, et al. Stage-matched nutritionguidance for patients at elevated risk for cardiovascular disease: a randomizedintervention study in family practice. J Fam Pract 2002;51:751–758.[PubMed]

16. Avenell A, Brown TJ, McGee MA, et al.What are the long-term benefits of weightreducing diets in adults? A systematic review of randomized controlled trials. JHum Nutr Diet 2004;17:317–335. [PubMed]

17. McTigue KM, Harris R, Hemphill B, et al. Screening and interventions for obesityin adults: summary of the evidence for the U.S. Preventive Services Task Force.Ann Intern Med 2003;139:933–949. [PubMed]

18. Dansinger ML, Gleason JA, Griffith JL, et al. Comparison of the Atkins, Ornish,Weight Watchers, and Zone diets for weight loss and heart disease risk reduction:a randomized trial. JAMA 2005;293:43–53.[PubMed]

19. Shaw K, O'Rourke P, Del Mar C, et al. Psychological interventions for overweightor obesity. In: The Cochrane Library, Issue 3, 2006. Chichester, UK: John Wiley& Sons, Ltd. Search date 2003.

20. Dunn C, Deroo L, Rivara FP. The use of brief interventions adapted from motiva-tional interviewing across behavioral domains: a systematic review. Addiction2001;96:1725–1742.[PubMed]

21. Tate DF, Jackvony EH, Wing RR. Effects of Internet behavioral counseling onweight loss in adults at risk for type 2 diabetes: a randomized trial. JAMA2003;289:1833–1836.[PubMed]

22. Stevens VJ, Obarzanek E, Cook NR, et al. Long-term weight loss and changesin blood pressure: results of the Trials of Hypertension Prevention, phase II. AnnIntern Med 2001;134:1–11.

23. Heshka S, Anderson JW, Atkinson RL, et al.Weight loss with self-help comparedwith a structured commercial program: a randomized trial. JAMA2003;289:1792–1798.[PubMed]

24. Carels RA, Darby LA, Cacciapaglia HM, et al. Reducing cardiovascular risk factorsin postmenopausal women through a lifestyle change intervention. J WomensHealth 2004;13:412–426.

25. Esposito K, Giugliano F, Di Palo C, et al. Effect of lifestyle changes on erectiledysfunction in obese men: a randomized controlled trial. JAMA2004;291:2978–2984.[PubMed]

26. Avenell A, Brown TJ, McGee MA, et al. What interventions should we add toweight reducing diets in adults with obesity? A systematic review of randomizedcontrolled trials of adding drug therapy, exercise, behaviour therapy or combina-tions of these interventions. J Hum Nutr Diet 2004;17:293–316. [PubMed]

27. Borg P, Kukkonen-Harjula K, Fogelholm M, et al. Effects of walking or resistancetraining on weight loss maintenance in obese, middle-aged men: a randomizedtrial. Int J Obes Relat Metab Dis 2002;26:676–683.

28. Fogelholm M, Kukkonen-Harjula K, Nenonen A, et al. Effects of walking trainingon weight maintenance after a very-low-energy diet in premenopausal obesewomen: a randomized controlled trial. Arch Intern Med2000;160:2177–2184.[PubMed]

29. Perri MG, Nezu AM, McKelvey WF, et al. Relapse prevention training and prob-lem-solving therapy in the long-term management of obesity. J Consult ClinPsychol 2001;69:722–726.[PubMed]

30. Kumanyika SK, Shults J, Fassbender J, et al. Outpatient weight management inAfrican-Americans: the Healthy Eating and Lifestyle Program (HELP) study. PrevMed 2005;41:488–502.[PubMed]

31. Harvey-Berino J, Pintauro S, Buzzell P, et al. Effect of internet support on thelong-term maintenance of weight loss. Obes Res 2004;12:320–329.[PubMed]

32. Leermakers EA, Perri MG, Shigaki CL, et al. Effects of exercise-focused versusweight-focused maintenance programs on the management of obesity. AddictBehav 1999;24:219–227.[PubMed]

33. Fogelholm M, Lahti-Koski M. Community health-promotion interventions withphysical activity: does this approach prevent obesity? Scand J Nutr2002;46:173–177.

34. Jeffery RW, French SA. Preventing weight gain in adults: the pound of preventionstudy. Am J Public Health 1999;89:747–751.[PubMed]

35. Simkin-Silverman LR, Wing RR, Boraz MA, et al. Lifestyle intervention can preventweight gain during menopause: results from a 5-year randomized clinical trial.Ann Behav Med 2003;26:212–220.[PubMed]

36. Harvey EL, Glenny AM, Kirk SF, et al. Improving health professionals' manage-ment and the organisation of care for overweight and obese people. In: TheCochrane Library, Issue 3, 2006. Chichester, UK: John Wiley & Sons, Ltd. Searchdate 2000.

37. Moore H, Summerbell CD, Greenwood DC, et al. Improving management ofobesity in primary care: cluster randomised trial. BMJ2003;327:1085–1088.[PubMed]

38. Pritchard DA, Hyndman J, Taba F. Nutritional counselling in general practice: acost effective analysis.J Epidemiol Community Health 1999;53:311–316.[PubMed]

39. Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA2002;288:2569–2578.[PubMed]

40. Law MR, Morris JK. By how much does fruit and vegetable consumption reducethe risk of ischaemic heart disease? Eur J Clin Nutr 1998;52:549–556.[PubMed]

41. Ness AR, Powles JW. Fruit and vegetables, and cardiovascular disease: a review.Int J Epidemiol 1997;26:1–13.[PubMed]



loo

d an

d lym

ph

diso

rders

http://www.ncbi.nlm.nih.gov/pubmed/10333851






























42. Ammerman AS, Lindquist CH, Lohr KN, et al.The efficacy of behavioral interven-tions to modify dietary fat and fruit and vegetable intake: a review of the evidence.Prev Med 2002;35:25–41. Search date not reported.[PubMed]

43. Miller ER, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitaminE supplementation may increase all-cause mortality. Ann Intern Med2005;142:37–46. Search date 2004.[PubMed]

44. Shekelle PG, Morton SC, Jungvig LK, et al. Effect of supplemental vitamin E forthe prevention and treatment of cardiovascular disease. J Gen Intern Med2004;19:380–389. Search date 2002.[PubMed]

45. Asplund K. Antioxidant vitamins in the prevention of cardiovascular disease: asystematic review. J Intern Med 2002;251:372–392. Search date 2001. [PubMed]

46. Eidelman RS, Hollar D, Hebert PR, et al. Randomized trials of vitamin E in thetreatment and prevention of cardiovascular disease. Arch Intern Med2004;164:1552–1556. Search date not reported.[PubMed]

47. Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of car-diovascular disease and cancer. The Women's Health Study: a randomizedcontrolled trial. JAMA 2005;294:56–65.[PubMed]

48. Vivekananthan DP, Penn MS, Sapp SK, et al. Use of antioxidant vitamins for theprevention of cardiovascular disease: meta-analysis of randomised trials. Lancet2003;361:2017–2023. Search date not reported. [PubMed]

49. Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX study: a randomized,placebo-controlled trial of the health effects of antioxidant vitamins and minerals.Arch Intern Med 2004;164:2335–2342.[PubMed]

50. Hooper L, Thompson RL, Harrison RA, et al. Omega 3 fatty acids for preventionand treatment of cardiovascular disease. In:The Cochrane Library, Issue 3, 2006.Chichester, UK: John Wiley & Sons, Ltd. Search date 2002.

51. Scientific Advisory Committee on Nutrition and Committee on Toxicity. Adviceon fish consumption: benefits and risks. London: The Stationary Office, 2004.

52. Panagiotakos DB, Pitsavos C, Polychronopoulos E, et al. Can a Mediterraneandiet moderate the development and clinical progression of coronary heart disease?A systematic review. Med Sci Monit 2004;10:RA193–RA198. Search date notreported.[PubMed]

Lee HooperLecturer in Research Synthesis

University of East AngliaNorwich

UK

Competing interests: LH is the author of 3 systematic reviews quoted in this review.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate ajudgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit andharms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices.Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical researchwe strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, thecategories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimatelyit is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullestextent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to anyperson or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, inci-dental or consequential, resulting from the application of the information in this publication.



loo

d an

d lym

ph

diso

rders










TABLE 1 RCT of strictly controlled sodium intake diets and their effects on blood pressure. [5]

Low sodium (65 mmol/day)Intermediate sodium (106 mmol/day)High sodium (142 mmol/day)Diet

Black people without hypertension: change in systolic blood pressure with DASH versus control (typical US diet). Both diets included 1-month periods of either high sodium, intermediate sodium, or low sodium

–5 mm Hg; P less than 0.001–2 mm Hg; P less than 0.050 mm Hg (baseline)Control (typical US diet)

–7 mm Hg; P value unclear–6 mm Hg; P value unclear–5 mm Hg; P value unclearDASH diet

Non-black people without hypertension: change in systolic blood pressure with DASH versus control (typical US diet). Both diets included 1-month periods of either high sodium, intermediate sodium, or low sodium

–4 mm Hg; P less than 0.001–2 mm Hg; P less than 0.050 mm Hg (baseline)Control (typical US diet)

–7 mm Hg; P value unclear–6 mm Hg; P value unclear–5 mm Hg; P value unclearDASH diet

DASH diet, Dietary Approaches to Stop Hypertension (a diet rich in fruit, vegetables, and low-fat dairy foods and low in saturated and trans fats).

© BMJ Publishing Group Ltd 2007. All rights reserved. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15


loo

d an

d lym

ph

diso

rders

Primary Prevention of CVD- Diet and Weight Loss

Documents

Transcript of Primary Prevention of CVD- Diet and Weight Loss