Wholegrain cereals for coronary heart disease (Review) - Teesside's ...

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Wholegrain cereals for coronary heart disease (Review) 

Kelly SAM, Summerbell CD, Brynes A, Whittaker V, Frost G 

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 

2009, Issue 1 

http://www.thecochranelibrary.com 


Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T A B L E O F C O N T E N T S 

HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 

ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 

PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 

BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 

OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 

METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 

Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 

RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 

DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 

AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 

ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 

REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 

CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 

DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 

Analysis 1.1. Comparison 1 Total cholesterol, Outcome 1 4 week outcomes. . . . . . . . . . . . . . . 50 

Analysis 1.2. Comparison 1 Total cholesterol, Outcome 2 All endpoint outcomes. . . . . . . . . . . . . 51 

Analysis 2.1. Comparison 2 LDL cholesterol, Outcome 1 4 week outcomes. . . . . . . . . . . . . . . 52 

Analysis 2.2. Comparison 2 LDL cholesterol, Outcome 2 All endpoint outcomes. . . . . . . . . . . . . 53 

Analysis 3.1. Comparison 3 HDL cholesterol, Outcome 1 4 week outcomes. . . . . . . . . . . . . . . 54 

Analysis 3.2. Comparison 3 HDL cholesterol, Outcome 2 All endpoint outcomes. . . . . . . . . . . . . 55 

Analysis 4.1. Comparison 4 Triglycerides, Outcome 1 4 week outcomes. . . . . . . . . . . . . . . . . 56 

Analysis 4.2. Comparison 4 Triglycerides, Outcome 2 All endpoint outcomes (Keenan data as SD). . . . . . . 57 

Analysis 4.3. Comparison 4 Triglycerides, Outcome 3 All endpoint outcomes (Keenan data as SEM). . . . . . . 58 

Analysis 5.1. Comparison 5 Body weight (kg), Outcome 1 All endpoint outcomes. . . . . . . . . . . . . 59 

WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 

HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 

CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 

DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 

SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 

INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 


Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 

i

[Intervention Review] 

Wholegrain cereals for coronary heart disease 

Sarah AM Kelly 1 , Carolyn D Summerbell 2 , Audrey Brynes 3 , Victoria Whittaker 4 , Gary Frost 5 

1 School of Dental Sciences, University of Newcastle, Newcastle upon Tyne, UK. 2 School of Medicine and Health, Wolfson Research 

Institute, Durham University, Stockton-on-Tees, UK. 3 Department of Dietetics, Hammersmith Hospital, London, UK. 4 School of 

Health and Social Care, University of Teesside, Middlesbrough, UK. 5 Department of Nutrition and Dietetics, Hammersmith Hospital, 

London, UK 

Contact address: Sarah AM Kelly, School of Dental Sciences, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK. 

s.a.m.kelly@newcastle.ac.uk. 

Editorial group: Cochrane Heart Group. 

Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009. 

Review content assessed as up-to-date: 14 January 2007. 

Citation: Kelly SAM, Summerbell CD, Brynes A, Whittaker V, Frost G. Wholegrain cereals for coronary heart disease. Cochrane 

Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005051. DOI: 10.1002/14651858.CD005051.pub2. 


Background 

A B S T R A C T 

There is increasing evidence from observational studies that wholegrains can have a beneficial effect on risk factors for coronary heart 

disease (CHD). 

Objectives 

The primary objective is to review the current evidence from randomised controlled trials (RCTs) that assess the relationship between 

the consumption of wholegrain foods and the effects on CHD mortality, morbidity and on risk factors for CHD, in participants 

previously diagnosed with CHD or with existing risk factors for CHD. 

Search strategy 

We searched CENTRAL (Issue 4, 2005), MEDLINE (1966 to 2005), EMBASE (1980 to 2005), CINAHL (1982 to 2005), ProQuest 

Digital Dissertations (2004 to 2005). No language restrictions were applied. 

Selection criteria 

We selected randomised controlled trials that assessed the effects of wholegrain foods or diets containing wholegrains, over a minimum 

of 4 weeks, on CHD and risk factors. Participants included were adults with existing CHD or who had at least one risk factor for 

CHD, such as abnormal lipids, raised blood pressure or being overweight. 

Data collection and analysis 

Two of our research team independently assessed trial quality and extracted data. Authors of the included studies were contacted for 

additional information where this was appropriate. 

Main results 

Ten trials met the inclusion criteria. None of the studies found reported the effect of wholegrain diets on CHD mortality or CHD 

events or morbidity. All 10 included studies reported the effect of wholegrain foods or diets on risk factors for CHD. Studies ranged in 

duration from 4 to 8 weeks. In eight of the included studies, the wholegrain component was oats. Seven of the eight studies reported 

lower total and low density lipoproteins (LDL) cholesterol with oatmeal foods than control foods. When the studies were combined in 



1

a meta-analysis lower total cholesterol (-0.20 mmol/L, 95% confidence interval (CI) -0.31 to -0.10, P = 0.0001 ) and LDL cholesterol 

(0.18 mmol/L, 95% CI -0.28 to -0.09, P < 0.0001) were found with oatmeal foods. However, there is a lack of studies on other 

wholegrains or wholegrain diets. 

Authors’ conclusions 

Despite the consistency of effects seen in trials of wholegrain oats, the positive findings should be interpreted cautiously. Many of 

the trials identified were short term, of poor quality and had insufficient power. Most of the trials were funded by companies with 

commercial interests in wholegrains. There is a need for well-designed, adequately powered, longer term randomised controlled studies 

in this area. In particular there is a need for randomised controlled trials on wholegrain foods and diets other than oats. 

P L A I N L A N G U A G E S U M M A R Y 

Wholegrain cereals for coronary heart disease 

Wholegrain foods encompass a range of products and examples are wholegrain wheat, rice, maize and oats. The term wholegrain also 

includes milled wholegrains such as oatmeal and wholemeal wheat. The evidence found by this review is limited to wholegrain oats, 

and to changes in lipids as an outcome. There is a lack of studies on other wholegrain foods or diets. There is some evidence from this 

review that oatmeal foods can beneficially lower lipid levels such as low density lipoproteins (LDL) cholesterol and total cholesterol in 

those previously diagnosed with risk factors for coronary heart disease (CHD) even with relatively short interventions. However, the 

results should be interpreted with caution because the trials found are small, of short duration and many were commercially funded. 

No studies were found that reported the effect of wholegrain foods or diets on deaths from, or occurrence of CHD. 

B A C K G R O U N D 

In western society, coronary heart disease (CHD) is the major 

cause of death. The prevalence of CHD is increasing worldwide 

(Murray 1997). In the UK, there were 238 deaths from CHD 

per 100,000 population in 1997 (OHE 1999). In England and 

Wales in 1996 one fifth of men and one eighth of women aged 

over 65 were treated for CHD in general practice (Carter 1999). 

CHD costs the health care system in the UK about £1750 million 

a year (BHF 2004). In addition, CHD costs the UK economy 

about £5300 million because of days lost due to death, illness and 

informal care of people with the disease (BHF 2004). 

A wholegrain contains the entire edible parts of a natural grain 

kernel. The structure of all whole grains is similar and includes 

the endosperm, germ and bran. Wholegrains are rich in dietary 

fibre, anti-oxidants, resistant starch, phyto-oestrogens and other 

important micronutrients such as vitamins and folic acid (Slavin 

2003). In the grain-refining process, most of the bran and some 

of the germ is removed, resulting in the loss of dietary fibre, vitamins, 

minerals, lignans, phyto-oestrogens, phenolic compounds 

and phytic acid. The remaining starchy endosperm is ground to 

produce refined white flours. 



Important grains in the western diet include wheat, rice, maize 

and oats. Wholemeal foods are made from wholegrains which have 

been milled to a finer texture rather than leaving them whole in 

the final product. Both wholegrain and wholemeal cereal foods 

are those grain foods which include the outer layers of the grain, 

including the bran and germ. Food Standards Australia and New 

Zealand (FSANZ 2004) have proposed a definition of the term 

wholegrain as ’ wholegrain means the intact grain, or the dehulled, 

ground, milled, cracked or flaked grain where the constituents - 

endosperm, germ and bran are present in such proportions that 

represent the typical ratio of those fractions occurring in the whole 

cereal, and includes wholemeal’ (FSANZ 2004). The proposal also 

relates to foods made from whole grains such as breads, breakfast 

cereals, pasta, biscuits, oats, rice and grain-based snack foods. Research 

has shown that such processing of whole-grains does not 

remove biologically important compounds (Slavin 2001). Nutritionally 

wholegrain and wholemeal foods are similar. 

The US Food and Drug Administration (FDA 1999) does not 

define wholegrain however since 1999 has permitted food manufacturers 

to make the following health claim on wholegrain food 

2

products ’diets rich in wholegrain foods and other plant foods and 

low in total fat, saturated fat and cholesterol may reduce the risk 

of heart disease and some cancers’ (FDA 1999). For the purpose 

of this health claim, wholegrain foods must contain 51% or more 

of wholegrain ingredients (bran, germ and endosperm) by weight 

per reference amount. 

A few epidemiological studies have specifically examined the association 

between intakes of wholegrain foods and risk of CHD. 

The Iowa Women’s Health study (Jacobs 1998; Jacobs 1999) of 

34,492 post menopausal women followed for 6 years found that 

a greater intake of wholegrain was associated with a reduced risk 

of death from CHD. The 10-year Nurses’ Health Study, a large 

prospective study of 75,521 women aged 38-63, found that increased 

wholegrain intake was associated with decreased risk of 

CHD (Liu 1999). The lower risk associated with higher wholegrain 

intake was not fully explained by its contribution to intakes 

of dietary fibre, folate, vitamin B6 and vitamin E. More recent 

trials have not demonstrated beneficial effects of vitamin E or folate/B6 

on CHD outcomes. The Atherosclerosis Risk in Communities 

(ARIC) study found a beneficial relationship between 

wholegrain consumption and the risk of total mortality and the 

incidence of coronary artery disease but not with the risk of ischaemic 

stroke (Steffen 2003). The study followed 15,792 people 

aged 45-64 for 11 years. A recent review of wholegrains and CVD 

risk (Seal 2006) concluded that there is an increasing body of evidence, 

including that from prospective population studies and 

epidemiological observational studies suggesting a strong inverse 

relationship between increased consumption of wholegrain foods 

and CVD risk. 

Other studies have focused on the relationship between cereal fibre 

and CHD. The amount of cereal fibre is much greater in wholegrain 

foods than in refined grain products so the cereal fibre intake 

is likely to mirror the wholegrain intake. In a large prospective 

study of 43,757 male health professionals, cereal fibre was associated 

with reduced risk for myocardial infarction, with a 29% 

decrease in risk for each 10 g increase in cereal fibre (Rimm 1996). 

A significant inverse association between total dietary fibre intake 

and risk of CHD was found in another large study of 68,782 

women who were followed for 10 years (Wolk 1999). There was a 

significant inverse relation with cereal fibre but not with vegetable 

or fruit fibre. Women in the highest quintile of cereal fibre had a 

34% lower risk of CHD events compared with those in the lowest 

quintile. However, the DART trial (Burr 1989) did not show any 

benefit of dietary fibre. 

Associations between wholegrain consumption and risk factors 

for CHD have also been reported. In the Framingham Offspring 

study, diets rich in wholegrains were inversely associated with total 

cholesterol, LDL cholesterol and body mass index (McKeown 

2002). A prospective study of women aged 38 to 63 years found 

that substituting wholegrain products for refined grain products 

may decrease the risk of Type 2 diabetes mellitus (Liu 2000). Di- 

abetes is a major risk factor for CHD. Reduced insulin sensitivity 

is another factor that contributes to the metabolic environment 

that predisposes to CHD (Reaven 1993). There is evidence of 

reduced insulin sensitivity at diagnosis in 60% of patients with 

CHD (Feranninni 1991). Wholegrain consumption improves insulin 

sensitivity in overweight and obese adults (Pereira 2002). 

O B J E C T I V E S 

The aim of this systematic review was to assess the effect of wholegrain 

foods or diets on total mortality from coronary heart disease 

(CHD), CHD events and morbidity or changes in major risk 

factors for CHD, in people with existing CHD or risk factors 

for CHD. All available randomised controlled trials and concurrent 

controlled trials and meta-analytic techniques were included 

where appropriate. 

M E T H O D S 

Criteria for considering studies for this review 

Types of studies 



Randomised controlled studies (RCTs). Cross-over studies and 

parallel studies were included. Trials were only included if outcome 

data could be collected (by communication with authors where 

necessary). 

Types of participants 

Non-institutionalised adults of either sex with diagnosed CHD, 

or with at least one major risk factor for CHD, were included. 

Major risk factors for CHD include overweight (body mass index 

>25), abdominal obesity, diabetes, family history of CHD, raised 

blood pressure, hypertension, abnormal lipid levels (high density 

lipoproteins (HDL) and low density lipoproteins (LDL) cholesterol, 

triglycerides or total cholesterol), impaired glucose tolerance, 

reduced insulin sensitivity, insulin resistance, hyperinsulinaemia, 

hyperglycaemia or abnormal clotting factors. Participants with 

myocardial infarction, coronary artery bypass graft, percutaneous 

transluminal coronary angioplasty, or who had angina pectoris or 

coronary artery disease defined by angiography were included. 

Participants without previously diagnosed CHD or risk factors for 

CHD were excluded. Children (age

Participants on medication were included with the exception of 

those on weight loss medication who were excluded. 

Types of interventions 

Studies were included if they compared the effect of individual 

wholegrain foods, or diets high in wholegrain foods, with other 

diets or foods with lower levels or no wholegrains. Comparisons 

were between diets with similar overall carbohydrate, fat, protein 

and energy levels. For the purpose of this review the term wholegrain 

includes foods based on milled wholegrains, such as wholemeal 

or oatmeal, where the components of the endosperm, bran 

and germ have not been removed. Studies had to have a minimum 

of four weeks intervention period (or follow-up period following 

dietary advice). 

Studies were not included if they were multiple component interventions, 

or interventions which incorporated factors other than 

wholegrain foods or diets, unless the effect of wholegrain foods 

or diets could be separated out from the other factors. Studies on 

foods which were based only on individual components (e.g. bran, 

germ or other components) of the grain were not included e.g. 

oat bran or wheatgerm. Studies that examined the effect of high 

fibre, dietary fibre or cereal fibre, but where the specific effect of 

wholegrain foods or diets could not be distinguished, were not 

included. 

Types of outcome measures 

Primary outcomes 

(1) Total CHD mortality. 

(2) Combined CHD events and morbidity (including fatal and 

non fatal myocardial infarction, angina, unplanned coronary 

artery bypass graft or percutaneous transluminal coronary angioplasty). 

(3) Changes in major risk factors for CHD including overweight, 

lipids (HDL and LDL cholesterol levels, triglycerides and total 

cholesterol), blood pressure, measures of diabetic control including 

changes in medication, glycosylated haemoglobin, glucose tolerance 

and control), insulin resistance, insulin sensitivity, clotting 

factors, hyperinsulinaemia, hyperglycaemia. 

Secondary outcomes 

(1) Measures of quality of life and attitudes to diets. 

Where reported, harms such as bloating, nausea, weight gain, difficulty 

in eating out, difficulty in preparing meals, excessive weight 

loss, intention to continue diet, were noted. 



Search methods for identification of studies 

(1) Electronic databases searched included the Cochrane Central 

Register of Controlled Trials (CENTRAL) on The Cochrane Library 

(Issue 3, 2005), MEDLINE (1966 to December Week 1 

2005), EMBASE (1980 to December Week 1 2005), CINAHL 

(1982 to December Week 1 2005) and ProQuest Digital Dissertations 

(2005). The searches were limited to studies in humans. 

There were no language restrictions for either searching or trial 

inclusion. 

(2) The reference lists of all included studies were searched in order 

to find other potentially eligible studies. 

(3) Known experts in the field were consulted to ensure completeness. 

(4) Published reviews in the area of wholegrains and CHD were 

also sought as a source of RCTs. 

The following search strategy was developed for MEDLINE, and 

used with a highly sensitive filter for identifying RCTs (Dickersin 

1994): 

1. wholegrain$.ab,ti. 

2. wholemeal$.ab,ti. 

3. wholewheat$.ab,ti. 

4. (whole adj3 grain$).ab,ti. 

5. (whole adj3 meal).ab,ti. 

6. (whole adj3 wheat).ab,ti. 

7. (whole adj3 food$).ab,ti. 

8. (wheat adj3 meal).ab,ti. 

9. cereal$.ab,ti. 

10. bread$.ab,ti. 

11. wheat$.ab,ti. 

12. oat$.ab,ti. 

13. rye$.ab,ti. 

14. barley$.ab,ti. 

15. maize$.ab,ti. 

16. corn.ab,ti. 

17. cornmeal.ab,ti. 

18. popcorn.ab,ti. 

19. sorghum$.ab,ti. 

20. (bulgar or bulghar).ab,ti. 

21. couscous$.ab,ti. 

22. grain$.ab,ti. 

23. porridge.ab,ti. 

24. rice$.ab,ti. 

25. millet$.ab,ti. 

26. exp CEREALS/ 

27. exp BREAD/ 

28. exp Dietary Fiber/ 

29. exp Coronary Disease/ 

30. exp Cardiovascular Diseases/ 

31. heart disease$.tw. 

32. coronary disease$.tw. 

33. chd.tw. 

34. cardiovascular.tw. 

4

35. angina.tw. 

36. cvd.tw. 

37. exp CHOLESTEROL/ 

38. exp Blood Pressure/ 

39. exp Obesity/ 

40. exp Insulin Resistance/ 

41. exp Diabetes Mellitus/ 

42. exp LIPIDS/ 

43. insulin resistance.ab,ti. 

44. insulin sensitivity.ab,ti. 

45. (glyc?emic adj3 control).ab,ti. 

46. or/1-28 

47. or/29-45 

48. 46 and 47 

The above search was adapted as necessary for the searches of 

EMBASE (Table 1), CINAHL (Table 2) The CENTRAL (Table 

3), and ProQuest Digital Dissertations (Table 4). 

Table 1. EMBASE search strategy 

Search terms 





5. (whole adj3 meal$).ab,ti. 





10. bread.ab,ti. 

11. breads.ab,ti. 





16. maize.ab,ti. 






22. couscous.ab,ti. 

23. grain.ab,ti. 

24. grains.ab,ti. 


26. exp Cereal/ 



29. exp Coronary Artery Disease/ 



5

Table 1. EMBASE search strategy (Continued) 

30. exp Cardiovascular Disease/ 



33. chd.tw. 



36. cvd.tw. 



39. exp OBESITY/ 




43. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 

or 25 or 26 or 27 or 28 

44. 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 

45. 43 and 44 

46. Controlled Study/ 

47. Clinical Trial/ 

48. random$.tw. 

49. compar$.ab,ti. 

50. control$.ab,ti. 

51. study.ab,ti. 

52. follow$ up.ab,ti. 

53. clinic$.ab,ti. 

54. blind$.ab,ti. 

55. Double Blind Procedure/ 

56. double$.ab,ti. 

57. 46 or 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55 or 56 

58. 45 and 57 

59. limit 58 to human 

Table 2. CINAHL search strategy 

Search terms 





5. (whole adj3 meal).ab,ti. 





10. bread$.ab,ti. 





6

Table 2. CINAHL search strategy (Continued) 



15. maize$.ab,ti. 






21. couscous$.ab,ti. 

22. grain$.ab,ti. 


24. rice$.ab,ti. 

25. millet$.ab,ti. 

26. exp CEREALS/ 



29. exp Coronary Disease/ 

30. exp Cardiovascular Diseases/ 



33. chd.tw. 



36. cvd.tw. 



39. exp Obesity/ 



42. exp LIPIDS/ 

43. insulin resistance.ab,ti. 

44. insulin sensitivity.ab,ti. 


46. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 26 

or 27 or 28 

47. 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 43 or 44 or 45 

48. 46 and 47 

49. clinical trial.pt. 

50. exp Clinical Trials/ 

51. (clin$ adj25 trial$).tw. 

52. ((singl$ or doubl$ or trebl$ or tripl$) adj (blind$ or mask$)).tw. 

53. exp PLACEBOS/ 

54. placebo$.tw. 

55. random$.tw. 

56. exp Evaluation Research/ 

57. exp Prospective Studies/ 

58. exp Random Assignment/ 

59. exp Random Sample/ 

60. exp Crossover Design/ 



7

Table 2. CINAHL search strategy (Continued) 

61. exp Comparative Studies/ 

62. 49 or 50 or 51 or 52 or 53 or 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 

63. 48 and 62 

Table 3. CENTRAL search strategy 

Search terms 

1. wholegrain$.af. 

2. wholemeal$.af. 

3. wholewheat$.af. 

4. (whole adj3 grain$).af. 

5. (whole adj3 meal$).af. 

6. (whole adj3 wheat$).af. 

7. (whole adj3 food$).af. 

8. (wheat adj3 meal$).af. 

9. cereals.af. 

10. bread$.af. 

11. wheat$.af. 

12. oat$.af. 

13. rye$.af. 

14. barley$.af. 

15. maize$.af. 

16. corn.af. 

17. cornmeal.af. 

18. popcorn.af. 

19. sorghum$.af. 

20. (bulgar or bulghar).af. 

21. couscous$.af. 

22. grain$.af. 

23. porridge$.af. 

24. (rice$:ti or rice$:ab).af. 

25. millet$.af. 

26. cereals.sh. 

27. bread.sh. 

28. dietary fiber.sh. 

29. (diet$ adj fiber$).af. 


31. or/1-30 

32. cardiovascular diseases.sh. 

33. (heart adj disease$).af. 

34. chd.af. 

35. (coronary adj3 disease$).af. 

36. cardiovascular.af. 

37. angina.af. 

38. cvd.af. 

39. cholesterol.sh. 

40. cholesterol.tw. 



8

Table 3. CENTRAL search strategy (Continued) 

41. (blood adj pressure).af. 

42. blood pressure.sh. 

43. hypertension.sh. 

44. hypertension.tw. 

45. obesity.sh. 

46. obesity.tw. 

47. obese.af. 

48. insulin resistance.af. 

49. (insulin adj resistance).af. 

50. (metabolic adj syndrome).af. 

51. diabetes mellitus.sh. 

52. diabetes.af. 

53. (insulin adj sensitivity).af. 

54. (glycemic adj3 control).af. 

55. (glycaemic adj3 control).af. 

56. hyperlipidemia.af. 

57. hyperlipidaemia.af. 

58. hyperlipidemia.sh. 

59. or/32-58 

60. 31 and 59 

1. wholegrain$.af. 

2. wholemeal$.af. 

3. wholewheat$.af. 

4. (whole adj3 grain$).af. 

5. (whole adj3 meal$).af. 

6. (whole adj3 wheat$).af. 

7. (whole adj3 food$).af. 

8. (wheat adj3 meal$).af. 

9. cereals.af. 

10. bread$.af. 

11. wheat$.af. 

12. oat$.af. 

13. rye$.af. 

14. barley$.af. 

15. maize$.af. 

16. corn.af. 

17. cornmeal.af. 

18. popcorn.af. 

19. sorghum$.af. 

20. (bulgar or bulghar).af. 

21. couscous$.af. 

22. grain$.af. 

23. porridge$.af. 

24. (rice$:ti or rice$:ab).af. 

25. millet$.af. 

26. cereals.sh. 

27. bread.sh. 

28. dietary fiber.sh. 




9

Table 3. CENTRAL search strategy (Continued) 


31. or/1-30 

32. cardiovascular diseases.sh. 

33. (heart adj disease$).af. 

34. chd.af. 

35. (coronary adj3 disease$).af. 

36. cardiovascular.af. 

37. angina.af. 

38. cvd.af. 

39. cholesterol.sh. 

40. cholesterol.tw. 

41. (blood adj pressure).af. 

42. blood pressure.sh. 

43. hypertension.sh. 

44. hypertension.tw. 

45. obesity.sh. 

46. obesity.tw. 

47. obese.af. 

48. insulin resistance.af. 

49. (insulin adj resistance).af. 

50. (metabolic adj syndrome).af. 

51. diabetes mellitus.sh. 

52. diabetes.af. 

53. (insulin adj sensitivity).af. 

54. (glycemic adj3 control).af. 

55. (glycaemic adj3 control).af. 

56. hyperlipidemia.af. 

57. hyperlipidaemia.af. 

58. hyperlipidemia.sh. 

59. or/32-58 

60. 31 and 59 

Table 4. ProQuest Digital Dissertations search strategy 

Search terms 

AB (wholegrain*)or AB (wholemeal)or AB (grain*) or AB (wheat*) or AB (cereal*) or AB ( bread* ) or AB (oat*) or AB (rye*) or AB 

(barley*) or AB (maize*) or AB (corn*) or AB ( sorghum*) or AB (bulgar*) or AB (bulghar*) or AB (couscous*)or AB (grain*) or AB 

(porridge*)or AB ( rice*) or AB (millet*) 

Data collection and analysis 

Trials selection 

For full details of the searches and selection of trials for the review 

see the Figure 1 (Moher 1999). 



10

The MEDLINE search identified 1937 potentially relevant articles, 

the EMBASE search 2286 articles and the CINAHL search 

338 articles. The potentially relevant articles from these three 

databases were imported into Endnote reference management software 

and combined. The combined articles were then de-duplicated 

using the Endnote software leaving 3976 combined hits. A 

further 968 search hits were identified from the CENTRAL search 

and 77 hits from ProQuest Digital Dissertations and screened separately. 

Figure 1. QUOROM flow chart. 



One reviewer scanned the titles and abstracts of each record retrieved 

from the searches. Articles were only rejected on initial 

screen if the reviewer could determine from the title and abstract 

that the article definitely did not meet the inclusion criteria for 

the review. 

When a title/abstract could not be rejected with certainty, the full 

text of the article was obtained for further evaluation and the entire 

article assessed. An in/out form was used to assess studies inclusion 

(or otherwise) into the review. If a trial was excluded at any time 

11

after this point, a record of both the article and exclusion reason 

was kept. 

A total of 92 potentially relevant full papers were identified:- 

81 from the combined MEDLINE, EMBASE and CINAHL 

searches; a further two full papers were identified from the CEN- 

TRAL search; a further 9 potentially relevant papers were identified 

from handsearching of relevant reviews. 

Of the 92 potentially relevant full papers, 81 were excluded and 

11 papers were included into the review. Two papers were from 

the same study (Pins 2002), so 10 studies in total were included 

in the review. 

Data extraction 

Original reports of trial results were extracted by two reviewers independently. 

Any differences between reviewers’ extraction results 

were resolved by discussion and, when necessary, in consultation 

with a third reviewer. 

The following data were extracted. 

1. General information: Published/unpublished, title, authors, 

source, country, year of publication, duplicate publications. 

2. Trial characteristics: Design, duration, randomisation (and 

method), allocation concealment (and method), blinding (outcome 

assessors), check of blinding. 

3. Intervention: Dietary information/foods provided, length of 

intervention, comparison interventions. 

4. Participants: Sampling (random/convenience), exclusion criteria, 

total number and number in comparison groups, gender/age, 

diagnosis of CHD or risk factors, similarity of groups at baseline, 

withdrawals/losses to follow-up, assessment of compliance, medications 

used, smoking status where provided. 

5. Outcomes: Outcomes as specified above including what was 

the main outcome assessed in the study, other events, length of 

follow-up. 

6. Results: For outcomes and times of assessment. 

Quality assessment of trials 

The quality of each trial was assessed based mainly on the quality 

criteria specified in the Cochrane Reviewers’ Handbook (Section 

4.1.6) (Higgins 2005). In particular the following factors were 

examined. 

1. Method of randomisation - each factor was marked as ’done’, 

’not done’ or ’unclear’. 

Could the study be described as randomised (including use of 

words such as ’random’, ’randomly’ and ’randomisation’)? 

Did the study describe the method of randomisation and was it 

an appropriate method? A method to determine the sequence of 

randomisation will be regarded as appropriate if it allows for each 

study participant to have the same chance of receiving each intervention 

and for the investigators to be unable to predict which 

treatment will be next. Methods of allocation using date of birth, 

date of admission, hospital numbers, or alternation were not regarded 

as appropriate. 

2. Concealment of allocation - this was scored A (adequate), B 

(unclear), C (inadequate), following criteria adopted from the 

Cochrane Reviewer’s Handbook (Section 4.1.6) (Higgins 2005) 

and Schulz et al (Schulz 1995). 

A - Adequate measures to conceal allocations such as central randomisation; 

serially numbered, opaque, sealed envelopes; or other 

descriptions with convincing concealment. 

B - Unclearly concealed trials, in which the authors either did not 

report allocation concealment at all, or reported an approach that 

did not fall into one of the categories in (A). 

C - Inadequately concealed trials, in which the method of allocation 

was not concealed, such as alteration methods or use of case 

record numbers. 

3. Blinding - each factor was marked as ’done’, ’not done’ or ’unclear’ 

With lifestyle interventions, such as the topic for this review, it is 

difficult to blind participants and those providing dietary advice. 

However, it is possible to blind outcome assessors and this were 

marked as ’done’, ’not done’ or ’unclear’. 

4. Intention-to-treat analysis - marked as ’done’, ’not done’ or 

’unclear’ 

Whether an intention-to-treat analysis was possible on all patients 

from the published data (i.e. whether there were any exclusions 

from the trial after randomisation) and the number of patients who 

were lost to follow-up. If there were no withdrawals this should 

have been stated in the article. An intention-to-treat analysis was 

considered adequate if outcome data was analysed for all participants 

randomised. 

Based on these criteria, studies were broadly subdivided into the 

following three categories, see Cochrane Handbook, section 6.7.1 

(Higgins 2005): 

A - all quality criteria met: low risk of bias. 

B - one or more of the quality criteria only partly met: moderate 

risk of bias. 

C - one or more criteria not met: high risk of bias. 

Data conversion 



For the purposes of pooling data, serum and plasma cholesterol 

measurements were converted to units of millimoles per litre 

(mmol/L). In some studies outcome data were reported in milligrams 

per decilitre (mg/dL). This was converted to mmol/L by 

multiplying by conversion factors of 0.0259 for total, HDL and 

LDL cholesterol; 0.0113 for triglycerides; and 0.0555 for glucose 

(JAMA 2001). When insulin was reported in µIU/mL(microunits 

of insulin per millilitre) it was converted to pmol/L (picomoles of 

insulin per litre) by multiplying by a conversion factor of 6.945 ( 

JAMA 2001). Where body weight was reported in pounds it was 

converted to kilograms by multiplying by a conversion factor of 

0.45. 

One study reported results for men and women separately ( 

Leinonen 2000). These results were combined for meta-analysis. 

12

Data analysis 

No data on CHD mortality or cardiovascular events were found 

in the studies included in the review. Relevant outcome data identified 

in the included trials were: 

(1) total cholesterol (mmol/L) Outcome 01; 

(2) LDL cholesterol (mmol/L) Outcome 02; 

(3) HDL cholesterol (mmol/L) Outcome 03; 

(4) triglycerides (mmol/L) Outcome 04; 

(5) body weight (kg) Outcome 05; 

Some data was also found on fasting glucose, fasting insulin, insulin 

resistance and blood pressure but there was insufficient data 

to combine in a meta-analysis. A number of studies also reported 

whether there were any side effects as a secondary outcome. 

When data were available, sufficiently similar and of sufficient 

quality, statistical analyses were performed using the RevMan software. 

Heterogeneity between trial results was tested for using a 

standard chi-squared test. A P value < 0.1 was used to indicate that 

significant heterogeneity was present. Heterogeneity was also examined 

using the I 2 statisitic (Higgins 2003). I 2 values over 50% 

indicate a substantial level of heterogeneity. Tests of heterogeneity 

were used for examining whether the observed variation in study 

results was compatible with variation expected with chance alone. 

If heterogeneity was found, then data were not pooled and we have 

attempted to determine potential reasons for heterogeneity by examining 

the study characteristics and populations. Where appropriate, 

recorded post treatment values were pooled using weighted 

mean differences in a fixed effects meta-analysis. No trials were 

found where participants were randomised by cluster/groups. 

Data has been pooled at the 4-week and end-of-study periods. In 

analyses using end of study data, data reported at the end of the 

study has been combined irrespective of the length of the study. 

Meta-analysis has not been performed when less than three studies 

reported outcome data, except for some sensitivity analyses where 

the exclusion of a study from the analysis results in the pooling of 

only two studies. 

Sensitivity analysis was used to take into account the influence of 

various factors e.g. (a) study quality, (b) exclusion of particularly 

small and underpowered trials. The results of sensitivity analysis 

are reported separately within each comparison section. 

Crossover studies 

One crossover study was incorporated into the meta-analysis ( 

Leinonen 2000). There was insufficient data published in the 

source paper to conduct paired analysis as recommended in the 

Cochrane Handbook (section 8.11.3) (Higgins 2005). The data 

incorporated into the meta-analysis was the final mean and standard 

deviation (SD) for the whole group at the end of each arm of 

the trial. Crossover and parallel studies have been presented separately 

within the meta-analysis and also combined. 

R E S U L T S 

Description of studies 

See: Characteristics of included studies; Characteristics of excluded 

studies; Characteristics of ongoing studies. 

Overview 



Details of the studies included in the review are shown in the 

table of characteristics of included studies. The column headed 

’methods’ presents the results of the quality assessment. 

Ten different studies were identified (from eleven papers) that met 

all the inclusion criteria for this review. No studies were found that 

reported the effect of wholegrain foods or diets on CHD mortality 

or CHD events and morbidity. All ten included studies report the 

effect of wholegrain foods or diets on major risk factors for CHD 

according to the inclusion criteria for this review outlined in the 

section on ’Types of outcome measures’. Eight of the studies were 

parallel randomised controlled trials (Davidson 1991; Johnston 

1998; Karmally 2005; Keenan 2002; Pins 2002; Reynolds 2000; 

Van Horn 1988; Van Horn 1991) and two studies were of randomised 

crossover design (Leinonen 2000; Pereira 2002). The total 

number of participants in the ten included studies was 914. 

One study (Pereira 2002) examined the effects of a varied diet 

containing wholegrain breakfast cereal, bread, rice, pasta, muffins, 

cookies and snacks and one study (Leinonen 2000) investigated the 

effects of wholegrain rye bread as part of the usual diet. However, 

in eight of the ten included studies the wholegrain component of 

the diet was oats (Davidson 1991; Johnston 1998; Karmally 2005; 

Keenan 2002; Pins 2002; Reynolds 2000; Van Horn 1988; Van 

Horn 1991; ). Three of the studies were based on a commercial 

wholegrain oat cereal (Cheerios) (Johnston 1998; Reynolds 2000; 

Karmally 2005). 

All studies included were over 4 weeks in length. In seven of the 

studies the intervention period was 6 weeks or less (Davidson 

1991;Johnston 1998; Karmally 2005; Keenan 2002; Leinonen 

2000; Pereira 2002; ; Reynolds 2000). Two studies continued for 

8 weeks (Van Horn 1988; Van Horn 1991) and one for 12 weeks ( 

Pins 2002) . All of the studies reported outcomes at the end of the 

intervention period. Some of the studies also reported outcomes 

at intermediate timescales (for example at 4 weeks). None of the 

studies reported follow-up outcomes beyond the end of the intervention 

period. 

Population and setting 

The inclusion criteria for this review specified that the participants 

should have at least one major risk factor for CHD. In six 

studies, participants were diagnosed with elevated cholesterol levels 

(Davidson 1991; Johnston 1998; Karmally 2005; Leinonen 

2000; Reynolds 2000; Van Horn 1991). Additionally, one study 

recruited a range of participants described as healthy but reports 

13

subgroup results for those with elevated cholesterol above the median 

at baseline (Van Horn 1988) and has also been included in 

the review because results for those with raised cholesterol levels 

can be separated out from the general population. In one study 

participants were diagnosed with hypertension (Pins 2002) and 

in another study, participants were both hypertensive and hyperinsulinemic 

(Keenan 2002). In one study, participants were both 

overweight and hyperinsulinemic (Pereira 2002). 

Most of the studies (nine) were conducted in the US and one 

in Finland (Leinonen 2000). Of the studies carried out in the 

US, four were carried out at the same University (University of 

Minnesota). However, it is not possible to determine from the 

published papers whether all four studies were conducted in the 

same clinic setting. 

Intervention 

The study by Leinonen et al (Leinonen 2000) determined the effects 

of wholemeal rye compared to white refined wheat bread in 

people with elevated serum cholesterol concentrations. The subjects 

were 18 men and 22 women with baseline serum cholesterol 

concentration of 6.4 +/- 0.2 mmol/L. The study design was a 2 

x 4 week crossover trial during which participants randomly consumed 

rye and refined wheat breads (20% of daily energy) as part 

of their usual diet for 4 weeks. There was a 4 week washout period 

between each intervention period. 

Pereira et al (Pereira 2002) compared diets (55% carbohydrate, 

30% fat, 15% protein) that included 6-10 servings of breakfast 

cereal, bread, rice, pasta , muffins, cookies and snacks of either 

whole or refined grains and measured the effect on insulin sensitivity 

in eleven overweight and obese adults aged 25 to 56 years. 

The study design was a crossover trial with two 6-week feeding 

periods with a washout of 6 weeks between feeding periods. The 

wholegrain diet was created by substitution of an equal volume of 

whole-grain food items for the refined grain products. 

Johnston et al (Johnston 1998) evaluated the effects of a wholegrain 

oat ready-to-eat cereal (Cheerios) in 135 men and women, 

aged 40-70 years, with elevated blood cholesterol levels (mean 

LDL-cholesterol levels of 130-190 mg/dL and triglycerides 130 mmHg, diastolic blood pressure >85 mmHg) 

and hyperinsulinaemic (>10uU/mL) men and women aged 27 to 

59 years. The study design was a randomised, controlled parallel 

group study with a 6 week intervention period. 

In a population of 88 men and women being treated for hypertension 

Pins et al (Pins 2002) compared the effect of wholegrain 

oat-based cereals with refined grain wheat-based cereals. Individuals 

in the wholegrain oats group received a daily serving of 60 

g of oatmeal and 77 g of oat squares. The cereal treatments were 

isocaloric and individuals in the control group consumed 65 g hot 

wheat cereal and 81 g of Kellog’s Crispix. The study was a randomised 

controlled parallel-group study of 12 weeks intervention 

in total, designed to determine the effect of wholegrain oat cereals 

on the need for antihypertensive medications. The study consisted 

of three 4-week phases: a baseline feeding phase, a medication reduction 

phase and a maintenance phase. The wholegrain oat and 

control cereals were administered during each of the four phases 

of the study. 

Van Horn (Van Horn 1988) examined the effect of an oatmealenhanced 

diet compared to a fat-modified diet recommended by 

the American Heart Association (AHA). All participants initially 

followed the AHA diet for 4 weeks and were then randomly assigned 

for 8 weeks to either an intervention group which continued 

to follow the AHA diet with the addition of 56 g (2 oz dry 

weight) oatmeal isocalorically substituted for other carbohydrate 

foods, or to a control group that continued to follow the AHA 

diet but consumed no oat products throughout the study. Participants 

in the study were healthy volunteers (aged 30 to 65 years) 

not taking lipid-altering medication. However, the results of the 

study are reported by subgroups with different cholesterol levels 

at baseline. The study has been included in this review because it 

reports subgroup results for those with elevated cholesterol above 

the median at baseline (n = 118) so the results for this group can 

be separated out from the overall results. 

Van Horn (Van Horn 1991) also examined the effect of an oatmeal 

enhanced diet in a study where all participants recruited to the 

trial were hypercholesterolemic (serum cholesterol levels > 5.20 

mmol/L), aged between 22 to 76 years. Individuals (n = 80) were 

randomised for 8 weeks to one of two groups, stratified by sex and 

pre-screen cholesterol level, above or below 6.34 mmol/L, prior 

to baseline visit. The intervention group was asked to consume 

two packets (56.7 g dry weight) of oatmeal per day, isocalorically 

14

substituted for other carbohydrate foods in their diet. The control 

group was asked to maintain usual intake throughout the study. 

Davidson (Davidson 1991) examined the effect of oatmeal at doses 

of either 28 g (1 oz), 56 g (2 oz) or 84 g (3 oz) dry weight in 

adults aged 30 to 60 years with elevated serum cholesterol levels, 

compared to a farina control group (farina is a refined grain made 

from the endosperm of the grain only, and does not contain bran 

or germ), over 6 weeks. The specific aim of this study was to examine 

the hypocholesterolemic effects of Beta-glucan in oatmeal, 

however, the study does meet the inclusion criteria for this review 

as oatmeal is classified as wholegrain. The study also included 

separate groups randomised to additional oatbran, however, these 

groups were not included in the meta-analysis as bran products 

are excluded from this review. 156 adults with LDL-cholesterol 

levels above 4.14 mmol/L or between 3.37 and 4.14 mmol/L with 

multiple risk factors were randomised to 6 intervention groups or 

to the farina control group. 

The study by Karmally et al (Karmally 2005) investigated the 

cholesterol-lowering effect of an oat cereal versus a corn cereal 

in mild to moderate hypercholesterolemic Hispanic Americans 

over 6 weeks. The oat cereal is described as commercial Cheerios 

in the paper and as an oat bran cereal. However, the author has 

confirmed to us (W. Karmally, personal communication) that the 

commercial Cheerios used are a wholegrain cereal. One hundred 

and fifty two men and women, ages 30 to 70 years with baseline 

LDL-cholesterol levels between 120 and 190 mg/dL (3.1 to 4.9 

mmol/L) and triglycerides < 400mg/dL (< 4.5 mmol/L). 

Funding 

Based on the details provided in the published papers, most of the 

studies included in this review were wholly or partly funded by 

commercial sources with interests in cereal products. 

The studies by Davidson and Van Horn 1991 were supported 

by Quaker Oats Company (Davidson 1991; Van Horn 1991). 

Additionally, the Pins study (Pins 2002) was supported in part 

by Quaker Oats who provided test cereals and financial support 

and Van Horn 1988 (Van Horn 1988) acknowledges assistance 

from Quaker Oats personnel but provides no further details on 

funding. 

The studies by Johnston (Johnston 1998) and Pereira (Pereira 

2002) were supported in part by General Mills Inc. The authors of 

the Karmally study acknowledge the support of General Mills Inc, 

but emphasise that the study sponsors had no role in study design, 

data collection, data analysis, data interpretation or writing of the 

report. Leinonen (Leinonen 2000) was supported in part by the 

Fazer Bakeries Ltd. and Vaasan and Vaasan Ltd. 

Two studies provided no information about funding (Keenan 

2002; Reynolds 2000). However, the first author of the Reynolds 

study gives an address based at General Mills Inc., US. The studies 

were both carried out at the University of Minnesota. General 

MIlls, the company that makes Cheerios is based in Minnesota. 

Risk of bias in included studies 

Overview 

All 10 studies had some methodological weaknesses according to 

criteria as set out in the Cochrane Handbook (Higgins 2005). 

None fulfilled all quality criteria. Two of the 10 studies were randomised 

crossover trials and 8 of the studies were parallel randomised 

controlled trials. 

Randomisation 

All of the trials mentioned randomisation without describing the 

randomisation process. None of the ten included studies reported 

on the method of randomisation so we could not tell if this was appropriate. 

Only one of the studies mentioned an attempt at allocation 

concealment (Reynolds 2000). Differences in baseline characteristics 

between intervention and control groups were discussed 

in all of the included studies, however in some studies randomisation 

does not appear to have been successful and differences in 

cholesterol levels between groups at baseline were bigger than the 

differences that the study was trying to measure (Reynolds 2000). 

Blinding 



Blinding of either the study participants or the providers of diets 

was not included in the protocol criteria for quality assessment of 

studies as it can be difficult to implement in lifestyle studies of the 

type included in the review. The original criteria for this systematic 

review only included blinding of outcome assessors. However, 

some of the included studies did report blinding of participants 

or providers of diets. 

One study reported that both the study participants and the experimental 

team who distributed the cereals were blinded (Reynolds 

2000). This was achieved by producing both the wholegrain cereal 

and the control cereal on the same commercial processing 

equipment and puffing the cereals into the same shape so that 

participants could not distinguish the cereals by shape. Both cereals 

were packaged so that the experimenter giving out the cereals 

could not tell the difference. Another study conducted by some 

of the same team members (Johnston 1998) may have used the 

same process to blind participants and the cereal providers. The 

study states the same information about using commercial cereal 

processing equipment and packaging but does not explicitly state 

that participants and providers were blinded (we have attempted 

to contact the research team for this study to clarify this without 

success). It is not clear from the published information whether 

outcome assessors were blinded in either of these studies. 

One study reported that the physician who dispensed the cereals 

and the physician responsible for BP measurement, blood draws 

and patient examinations was blinded (Pins 2002). 

15

One study was reported to be single-blinded (Davidson 1991) 

but it was not clear from the published details which part of the 

process was blinded. One study reported that blinding of outcome 

assessors was done for blood pressure but did not state whether 

the process of sampling and measuring lipids was blinded (Keenan 

2002). 

In the other five included studies no details were given about blinding 

( Karmally 2005; Leinonen 2000; Pereira 2002; Van Horn 

1988; Van Horn 1991). 

Crossover studies 

A carryover effect may occur in a crossover trial when the effects 

of the treatment in the first period of the trial continue over to the 

second period. In such cases, the results from the second period 

may be inaccurate. A washout period is the time when no intervention 

occurs between the two treatment periods and should be 

long enough to allow the effects from the first treatment period to 

completely disappear. 

Both of the included studies that were crossover trials reported 

an adequate washout period between diet phases. The washout 

periods were 4 weeks (Leinonen 2000) and 6-9 weeks (Pereira 

2002). Meta-analysis has been carried out on crossover and parallel 

studies separately to determine if the study design has any influence 

on the overall results. 

Potential confounders 

Body weight 

Of the 10 included studies, nine stated that the dietary programmes 

were designed to maintain body weight in both the 

intervention and control groups (Johnston 1998; Keenan 2002; 

Leinonen 2000; Pereira 2002; Pins 2002; Reynolds 2000; Van 

Horn 1988; Van Horn 1991). One other study does not specifically 

state this but it is implied in the text (Davidson 1991). 

Nine of the 10 included studies reported no significant change in 

body weight throughout the study in either the intervention or 

control groups (Davidson 1991; Johnston 1998; Keenan 2002; 

Leinonen 2000; Pereira 2002; Pins 2002; Reynolds 2000; Van 

Horn 1991). One study reported no difference after 8 weeks, but 

a small increase after 4 weeks in the mean weight of the oatmeal 

group (+0.2 lb) compared to the control group (-0.6 lb) (P = 0.039 

for the intergroup difference) (Van Horn 1988). 

Medication status 

Most of the studies excluded participants on lipid-lowering medication 

(Davidson 1991; Karmally 2005; Leinonen 2000; Pereira 

2002; Van Horn 1988; Van Horn 1991 ). Three studies included 

participants on beta-blockers as long as the dose was kept constant 

throughout the study (Johnston 1998; Reynolds 2000). The study 

by Johnston excluded subjects taking certain drugs e.g. corticosteroids, 

androgens or lipid-lowering drugs but did allow subjects 

to take other drugs potentially affecting lipids such as beta-blockers, 

estrogen, estrogen progestin, thiazide diuretics and thyroid 

hormones as long as they were on stable doses (Johnston 1998). 

In one study the major outcome was reduction in medication 

status and improvement in blood pressure control (Pins 2002), 

so participants were allowed no more than one anti-hypertensive 

medication and/or one diuretic medication. 

In one study medication status was not reported (Keenan 2002). 

Smoking status 

Smokers were excluded from three of the studies (Keenan 2002; 

Pereira 2002; Pins 2002) and smoking status was not reported 

in five studies (Davidson 1991; Karmally 2005; Leinonen 2000; 

Van Horn 1988; Van Horn 1991). The inclusion criteria for two 

studies allowed participants to smoke (Johnston 1998; Reynolds 

2000). In both studies, smoking remained constant throughout 

the study for both intervention and control groups. 

Dietary fibre 

Any reported differences in dietary fibre content between the treatment 

and control groups have been reported in the ’Notes’ section 

of the table of ’Characteristics of included studies’. The focus of 

this review is to assess whether wholegrain diets have a beneficial 

effect on CHD and major risk factors for CHD in order to provide 

recommendations as to whether more wholegrain foods should be 

included in the diets of the general public. All wholegrains contain 

dietary fibre. Dietary fibre content may potentially be a major 

contributing factor to any differences between wholegrain diets 

and the control diets but is not the primary focus of this review. 

Compliance to diet 

None of the studies reported any problems with compliance to 

the diets. 

Power 



Power calculations were conducted in four of the 10 studies included 

in this review (Davidson 1991; Leinonen 2000; Pins 2002; 

Reynolds 2000). The sample size of the study by Leinonen ( 

Leinonen 2000) was based on 80% power to detect a difference in 

serum total cholesterol concentration of 0.4 to 0.5 mmol/L based 

on a significance level of 0.05. The study by Davidson (Davidson 

1991) was designed to have an 90% chance of detecting a difference 

in lipid levels of 0.39 mmol/L at significance 0.05. It is not 

clear from the published details whether the power calculations in 

the Davidson study took into account that the participants were 

randomised to a total of seven groups. Such differences of 0.3- 

0.5 mmol/L are reasonable for dietary intervention studies but the 

16

differences measured in the studies included in this review were 

often lower than this. The sample size calculation in the Keenan 

study was based on a level of significance set at 0.05 and power of 

80% to detect a 15% difference in medication reduction (Keenan 

2002). While the study by Reynolds did report that power calculations 

were done before the study, the calculations showed only 

a 53% chance of detecting a 3.8% mean drop in cholesterol assuming 

25 subjects in each group at a significance level of 0.05. 

In the paper, however, the analysis was actually based on less than 

25 subjects in each group (21 and 22 subjects) so the power of the 

study is likely to have been less than 53%. None of the other five 

included studies reported power calculations. In two of the studies 

that did not report power calculations, the number of participants 

included in the analysis was very small. In the cross-over study 

by Pereira only 12 people were randomised (Pereira 2002). In the 

study by Keenan, there were only 10 in the treatment group and 

eight in the control group (Keenan 2002). 

Population 

In all 10 studies included in the review, the participants were diagnosed 

with risk factors for CHD at baseline. In seven studies 

the participants had raised cholesterol (Davidson 1991; Johnston 

1998; Karmally 2005; Leinonen 2000; Reynolds 2000; Van Horn 

1988; Van Horn 1991), in two studies they were hypertensive ( 

Keenan 2002; Pins 2002) and in one study they were overweight 

(Pereira 2002). The study by Pereira was not included in the analyses 

as it reported a different outcome (insulin sensitivity) than 

the other studies. The studies on hypertensive participants both 

reported lower baseline cholesterol levels than most of the other 

studies but the results were consistent with the studies on hypercholesterolemic 

participants with lower cholesterol reported in the 

wholegrain group than the control group. 

Intention to treat (ITT) analysis 

Only one of the 10 included studies reported an intention-totreat 

(ITT) analysis along with an analysis of those compliant 

to diet (Davidson 1991). However, the reported ITT analysis is 

considered to be inadequate because it did not incorporate data 

for all subjects randomised (156 subjects were randomised, but the 

ITT analysis only took into account data from 148 subjects). A 

further two studies (Leinonen 2000; Pins 2002) did not formally 

report an ITT analysis but in both cases all the subjects who were 

randomised were included in the analysis and no drop-outs were 

reported. None of the other studies conducted ITT analysis. 

Quality assessment 

Table 5. Summary of main results (comparison wholegrain versus control) 

None of the studies met all of the quality assessment parameters 

specified for this review based on the criteria outlined in the 

Cochrane Reviewer’s handbook (Higgins 2005) and listed above 

in the section on ’Quality Assessment of Trials’ in ’Methods of the 

review’. Based on these criteria all 10 of the included studies would 

be classified as quality C. This means that one or more quality 

criteria were not met and the studies have a high risk of bias. None 

of the studies were excluded on the basis of a low quality score 

as all of the 10 included studies were graded at the same level of 

quality (C) based on the Cochrane criteria. 

As all the trials were rated at the same level, sensitivity analysis on 

the basis of quality was not carried out. 

Effects of interventions 

Heterogeneity was not found in the pooled analyses for total 

cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. 

Heterogeneity was found for the combined body weight data so 

the results of pooled analyses are not shown in the graphs, only 

the sub-totals (Comparison 05). 

A summary of the main results is shown in additional Table 5. 

Outcome Intervention No. of studies Pooled result Type of wholegrain 

Outcome measure (sensitivity 

analyses) 

Total cholesterol All end of study outcomes 

- (without Reynolds 

study) 

All end of study outcomes 

(mmol/L) 

8 Parallel studies 0.19 (95% CI 

-0.30 to -0.08), P = 0.0005 

7 Parallel -0.22 (95% CI-0.33 

to -0.10), P = 0.0002 



Oats 

Oats 

17

Table 5. Summary of main results (comparison wholegrain versus control) (Continued) 

- (without Reynolds/ 

Keenan) 


Total cholesterol All end of study outcomes 


study) 


Keenan) 



LDL cholesterol All end of study outcomes 


study) 


study) 



LDL cholesterol All end of study outcomes 


study) 


Keenan) 



HDL cholesterol All end of study outcomes 


study) 


Keenan) 



6 Parallel -0.21 (95% CI-0.32 

to -0.09), P = 0.0006 

9 Parallel and crossover studies - 

0.20 (95% CI-0.31 to -0.10), 

P = 0.0001 


0.23 (95% CI-0.33 to -0.12), 

P < 0.0001 


0.22 (95% CI-0.33 to -0.10), 

P = 0.0002 

8 Parallel studies -0.18 (95% 

CI-0.28 to -0.09), P = 0.0001 


CI-0.30 to -0.10), P < 0.0001 


CI-0.29 to -0.09), P = 0.0002 


0.18 (95% CI-0.28 to -0.09), 

P < 0.0001 

8 Parallel and crossover studies 

-0.20 (95% CI-0.30 to 0.11), 

P < 0.0001 


0.19 (95% CI-0.29 to -0.10), 

P < 0.0001 

6 Parallel studies 0.00 (95% CI- 

0.05 to -0.05), P = 0.95 


0.06 to -0.05), P = 0.88 


CI-0.07 to -0.05), P = 0.87 



Oats 

Oats and rye 

Oats and rye 

Oats and rye 

Oats 

Oats 

Oats 

Oats and rye 

Oats and rye 

Oats and rye 

Oats 

Oats 

Oats 

18


HDL cholesterol All end of study outcomes 


study) 


Keenan) 



Triglycerides All end of study outcomes 


study) 


Keenan) 



Triglycerides All end of study outcomes 


study) 


Keenan) 




0.00 (95% CI-0.05 to 0.05), 

P = 0.95 


0.00 (95% CI-0.06 to 0.05), 

P = 0.89 


0.00 (95% CI-0.06 to 0.05), 

P = 0.87 


0.11 to 0.13), P = 0.83 


CI-0.14 to 0.11), P = 0.81 


0.13 to 0.13), P = 1.00 


0.01 (95% CI-0.09 to 0.11), 

P = 0.86 


-0.01 (95% CI-0.11 to 0.09), 

P = 0.85 


0.00 (95% CI-0.11 to 0.11), 

P = 1.00 



Oats and rye 

Oats and rye 

Oats and rye 

Oats 

Oats 

Oats 

Oats and rye 

Oats and rye 

Oats and rye 

19


Comparison 01 Total cholesterol 

4 week outcomes Comparison 01 Outcome 01 

Three parallel studies (Reynolds 2000; Van Horn 1988; Van Horn 

1991) and one crossover study (Leinonen 2000) reported outcomes 

at 4 weeks. The three parallel studies were based on wholegrain 

oatmeal and the crossover study was on wholegrain rye. 

On an intra-study basis, two of the three parallel studies in oats 

reported lower total cholesterol at 4 weeks in the wholegrain groups 

than in the control groups (Van Horn 1988; Van Horn 1991). 

In the other study (Reynolds 2000), a bigger reduction in total 

cholesterol was observed in the wholegrain group when the preand 

post-treatment data were compared. However, this effect is 

not evident from the post-treatment data presented in the metaanalysis 

because of a large baseline difference between the groups 

and insufficient power to detect the small changes in cholesterol 

observed. The crossover study on rye also reported lower total 

cholesterol at 4 weeks in the wholegrain group (Leinonen 2000). 

The difference between the groups was not significant in any of 

the studies. 

When the 4 week results from the three parallel studies (all oats) 

were pooled in a meta-analysis, there was no evidence of an effect 

on total cholesterol in the wholegrain group compared to the 

control group, although the direction of the effect favoured a reduction 

in total cholesterol on the wholegrain diets. The weighted 

mean difference was -0.12 mmol/L (95% CI -0.32 to 0.09). Addition 

of the one crossover study (rye) to the analysis did not change 

the result markedly and gave weighted mean difference of -0.16 

mmol/L (95% CI -0.34 to 0.01). 

In a sensitivity analysis, the data was re-analysed without the study 

by Reynolds et al because of the baseline differences between the 

groups. With only two parallel studies in the sensitivity analysis, 

there remained no evidence of an effect on total cholesterol with 

a weighted mean difference of -0.20 mmol/L (95% CI -0.46 to 

-0.06). However, when both parallel and crossover studies were 

included in the analysis, there was some evidence for a reduction in 



total cholesterol in the wholegrain group (effect size -0.24 mmol/L, 

95% CI -0.45 to -0.03, P = 0.03). 

All end-of-study outcomes Comparison 01 Outcome 02 

In total, eight parallel studies (Davidson 1991; Johnston 1998; 

Karmally 2005; Keenan 2002; Pins 2002; Reynolds 2000; Van 

Horn 1991; Van Horn 1988) and one crossover study (Leinonen 

2000) reported total cholesterol outcomes. All eight parallel studies 

were based on wholegrain oatmeal and the crossover study was on 

wholegrain rye. 

On an intra-study basis, seven of the eight parallel studies in oats 

reported lower total cholesterol in the wholegrain groups than 

in the control groups (Davidson 1991; Johnston 1998; Karmally 

2005; Keenan 2002; Pins 2002; Van Horn 1988; Van Horn 1991). 

The difference between the groups was significant in one study ( 

Pins 2002). In the other study (Reynolds 2000), a bigger reduction 

in total cholesterol was observed in the wholegrain group when 

the pre- and post-treatment data were compared. However, this 

effect is not evident from the post-treatment data presented in 

the meta-analysis because of a large baseline difference between 

the groups and insufficient power to detect the small changes in 

cholesterol observed. The one crossover study on rye also reported 

lower total cholesterol in the wholegrain group (Leinonen 2000) 

but the difference was not significant. 

When the results from the eight parallel studies (all oats) were 

pooled in a meta-analysis, there was evidence of an effect on total 

cholesterol in the wholegrain group compared to the control 

group, and the direction of the effect favoured lower total cholesterol 

on the wholegrain diets. The weighted mean difference was 

-0.19mmol/L (95% CI -0.30 to -0.08, P = 0.0005). Addition of 

the one crossover study (rye) to the analysis had little effect on the 

combined results (weighted mean difference -0.20, 95% CI -0.31 

to -0.10, P = 0.0001). 

Sensitivity analysis was conducted without the study by Reynolds. 

The effect increased slightly and remained significant (-0.23 95% 

CI -0.33 to -0.12). Additionally, removal of the study by Keenan 

20

ecause of the small number of subjects had little effect on the 

analysis (weighted mean difference -0.22 mmol/L, 95% CI -0.33 

to -0.10). 

Total cholesterol - summary of results 

There is evidence that total cholesterol is lower on diets containing 

oatmeal compared to diets based on refined grains. Eight of nine 

studies that reported total cholesterol as an outcome were based on 

oatmeal. When the end-of-study results from the eight studies were 

combined, the weighted mean difference was -0.19 mmol/L (95% 

CI -0.30 to -0.08, P = 0.0005) for the oatmeal diets compared 

to the refined grain diets. A similar effect was seen from three 

studies that provided data at 6 weeks intervention (weighted mean 

difference -0.23, 95% CI -0.40 to -0.05, P = 0.01), but not at 4 

weeks (except in one sensitivity analysis). 

There is insufficient evidence to make any conclusions about 

wholegrain diets other than oatmeal. Only one other study on 

other wholegrains was found. When this study on rye was pooled 

with the other data for oatmeal, it made little difference to the 

results. 

Comparison 02 LDL cholesterol 


Three parallel studies (Reynolds 2000; Van Horn 1988; Van Horn 

1991) and one crossover study (Leinonen 2000) reported LDL 

cholesterol at 4 weeks. The three parallel studies were based on 

wholegrain oatmeal and the crossover study was on wholegrain 

rye. 

On an intra-study basis, two of the three parallel studies in oats reported 

lower LDL cholesterol at 4 weeks in the wholegrain groups 

than in the control groups (Van Horn 1988; Van Horn 1991). The 

difference between the groups was significant in one of the studies 

(Van Horn 1988). In the other study by Reynolds et al, a bigger reduction 

in LDL cholesterol was observed in the wholegrain group 

when the pre- and post-treatment data were compared. However, 

this effect is not evident from the post-treatment data presented 

in the meta-analysis because of a large baseline difference between 

the groups and insufficient power to detect the small changes in 

cholesterol observed. In the one crossover study on rye, lower LDL 

cholesterol was also reported in the wholegrain group (Leinonen 

2000), but the difference was not significant. 

When the 4 week results from the three parallel studies (all oats) 

were pooled, there was no evidence of an effect on LDL cholesterol 

in the wholegrain group compared to the control group, although 

the direction of the effect favoured a reduction in LDL cholesterol 

on the wholegrain diets and was close to significance (P = 0.07). 

The weighted mean difference was -0.19 mmol/L (95% CI -0.39 

to 0.02). However, the combined analysis did become significant 



when the one crossover study (rye) was included in the analysis. 

The weighted mean difference was -0.19 mmol/L (95% CI -0.37 

to -0.01, P = 0.04). 


by Reynolds et al because of differences between groups at baseline. 

With only two parallel studies in the sensitivity analysis, there was 

evidence of an effect on LDL cholesterol with a weighted mean 

difference of -0.31 mmol/L (95% CI -0.56 to -0.05). Addition of 

the crossover study to the analysis had little effect (effect size -0.28 

mmol/L, 95% CI -0.49 to -0.06). 


In total, eight parallel studies (Davidson 1991; Johnston 1998; 

Karmally 2005; Keenan 2002; Pins 2002; Reynolds 2000; Van 

Horn 1988; Van Horn 1991) and one crossover study (Leinonen 

2000) reported LDL cholesterol outcomes. All eight parallel studies 

were based on wholegrain oatmeal and the crossover study was 

on wholegrain rye. 

On an intra-study basis, seven of the eight parallel studies in oats 

reported lower LDL cholesterol in the wholegrain groups than 

in the control groups (Davidson 1991; Johnston 1998; Karmally 

2005; Keenan 2002; Pins 2002; Van Horn 1988; Van Horn 1991). 

The difference between the groups was significant in three studies 

(Johnston 1998; Karmally 2005; Pins 2002). In the other study 

by Reynolds et al, a bigger reduction in LDL cholesterol was observed 

in the wholegrain group when the pre- and post-treatment 

data were compared. However, this effect is not evident from the 

post-treatment data presented in the meta-analysis because of a 

large baseline difference between the groups and insufficient power 

to detect the small changes in cholesterol observed. In the one 

crossover study in rye, LDL cholesterol was also lower in the wholegrain 

group (Leinonen 2000) but the difference was not significant. 

When the results from the eight parallel studies (all oats) were 

pooled in a meta-analysis, there was evidence of an effect on 

LDL cholesterol in the wholegrain group compared to the control 

group, and the direction of the effect favoured lower LDL cholesterol 

on the wholegrain diets. The weighted mean difference was 

-0.18 mmol/L (95% CI -0.28 to -0.09, P = 0.0001). Addition of 

the one crossover study (rye) to the analysis had little effect on the 

combined results (weighted mean difference -0.18, 95% CI -0.28 

to -0.09, P < 0.0001). 

Sensitivity analysis was conducted without the study by Reynolds. 

When all the studies were included, the effect increased slightly and 

remained significant. Effect size -0.20 (95% CI -0.30 to -0.11). 

Similarly, removal of the study by Keenan, because of the small 

number of subjects, had little effect on the analysis (weighted mean 

difference -0.19 mmol/L (95% CI -0.29 to -0.10, P < 0.0001). 

21

LDL cholesterol - summary of results 

Eight of nine studies that reported LDL cholesterol as an outcome 

were based on oatmeal. There is evidence that LDL cholesterol is 

lower on diets containing oatmeal compared to diets based on refined 

grains. When the end-of-study results from the eight studies 

were combined, the weighted mean difference was -0.18 mmol/L 

(95% CI -0.28 to -0.09, P < 0.0001) for the oatmeal diets compared 

to the refined grain diets. A similar effect was seen from 

three studies that provided data at 6 weeks intervention (weighted 

mean difference -0.25, 95% CI -0.39 to -0.10, p= 0.0008), but 

not at 4 weeks (except in one sensitivity analysis). 




with the other data for oatmeal, it made little difference to the 

overall results. 

Comparison 03 HDL cholesterol 


Two parallel studies ( Reynolds 2000; Van Horn 1991) and one 

crossover study (Leinonen 2000) reported outcomes at 4 weeks. 

The two parallel studies were based on wholegrain oatmeal and 

the crossover study was on wholegrain rye. 

On an intra-study basis, the two parallel studies reported slightly 

higher HDL cholesterol in the wholegrain group (Reynolds 2000; 

Van Horn 1991) and the crossover study (Leinonen 2000) showed 

no difference between groups, but the difference between the 

wholegrain and control groups was not significant in any of the 

studies. 

When the 4 week results from all three studies were pooled in a 

meta-analysis, there was no evidence of an overall effect on HDL 

cholesterol. Parallel and crossover studies are reported together 

because there are only three studies. The weighted mean difference 

between the wholegrain and control groups was 0.03 mmol/L 

(95% CI -0.06 to 0.11), slightly higher in the wholegrain group. 

The result did not differ markedly in a sensitivity analysis, without 

the study by Reynolds et al. 


In total six parallel studies (Davidson 1991; Johnston 1998; 

Karmally 2005; Keenan 2002; Reynolds 2000; Van Horn 1991) 

and one crossover study (Leinonen 2000) reported HDL cholesterol 

outcomes. All six parallel studies were based on wholegrain 

oatmeal and the crossover study was on wholegrain rye. 

On an intra-study basis, four of the six parallel studies reported 

higher HDL cholesterol in the wholegrain groups than in the 

control groups (Davidson 1991; Johnston 1998; Keenan 2002; 



Reynolds 2000), two studies reported lower HDL cholesterol in 

the wholegrain group ( Karmally 2005; Van Horn 1991). The 

one crossover study in rye reported no difference between the 

groups (Leinonen 2000). The difference between the groups was 

not significant in any of the studies. 

When the results from the six parallel studies (all oats) were 

pooled in a meta-analysis, there was no evidence of an effect on 

HDL cholesterol in the wholegrain group compared to the control 

group. The weighted mean difference was 0.00 mmol/L (95% CI 

-0.05 to 0.05, P = 0.95). Addition of the one crossover study (rye) 

to the analysis had no effect on the combined results. Also, sensitivity 

analyses without either the Reynolds study and additionally 

without the Keenan study had no effect on the combined result. 

HDL cholesterol - summary of results 

There is no evidence of a difference in HDL cholesterol on diets 

containing oatmeal compared to diets based on refined grains from 

outcome data from pooling of data at 4 weeks, 6 weeks or from 

the pooling of all end-of-study data. 




with the other data for oatmeal, it made no difference to the results. 

Comparison 04 Triglycerides 


Two parallel studies (Reynolds 2000; Van Horn 1991) and one 

crossover study (Leinonen 2000) reported outcomes at 4 weeks. 

The two parallel studies were based on wholegrain oatmeal and 

the crossover study was on wholegrain rye. 

On an intra-study basis, one of the two parallel studies in oats 

reported higher triglycerides at 4 weeks in the wholegrain groups 

than in the control groups (Van Horn 1991), one reported lower 

mean triglycerides (Reynolds 2000). The one crossover study in 

rye reported no difference between the groups (Leinonen 2000). 


the studies. 

When the 4 week results from all three studies were pooled in 

a meta-analysis, there was no evidence of an effect on triglycerides 

in the wholegrain group compared to the control group. 

The weighted mean difference was 0.01 mmol/L (95% CI -0.13 

to 0.16, P = 0.84). 


by Reynolds et al. With only two studies in the sensitivity analysis 

(one crossover and one parallel), there remained no evidence of 

an effect on triglycerides with a weighted mean difference of 0.05 

mmol/L (95% CI -0.11 to 0.20). 

22

All end-of-study outcomes (Comparison 04 Outcomes 02- 

03) 

In total, six parallel studies (Davidson 1991; Karmally 2005; 

Keenan 2002; Pins 2002; Reynolds 2000; Van Horn 1991) and 

one crossover study (Leinonen 2000) reported triglycerides as an 

outcome. All six parallel studies were based on wholegrain oatmeal 

and the crossover study was on wholegrain rye. 

On an intra-study basis, three of the parallel studies in oats reported 

lower triglycerides in the wholegrain groups than in the control 

group (Davidson 1991; Pins 2002; Reynolds 2000), three studies 

reported higher triglycerides in the wholegrain group (Karmally 

2005; Keenan 2002; Van Horn 1991). The one parallel study in 

rye reported no difference between the groups (Leinonen 2000). 


the studies. 

When the results from the six parallel studies (all oats) were pooled 

in a meta-analysis, there was no evidence of an effect on triglycerides 

in the wholegrain group compared to the control group 

(Comparison 04 Outcome 02). The weighted mean difference was 

0.01 mmol/L (95% CI -0.11 to 0.13, P = 0.83). Addition of the 

one crossover study (rye) to the analysis had little effect on the 

combined results (weighted mean difference 0.01, 95% CI -0.09 

to 0.11, P = 0.86). The study by Keenan reports the data as mean 

triglycerides and standard error of the mean (SEM). However, the 

data appears to be SD rather than SEM. The pooled data was analysed 

assuming the reported data was SD (Comparison 04 Outcome 

02) which gave weighted mean difference 0.01 (95% CI -0.09 to 

0.11) and then assuming the reported data was SEM (Comparison 

04 Outcome 03) which gave weighted mean difference -0.01 (95% 

CI -0.11 to 0.09). Little difference was seen in the pooled results 

using SD or SEM for this study. 

Sensitivity analysis was conducted without the studies by Reynolds 

and Keenan. There was little effect on the combined results and 

the weighted mean difference between the wholegrain and control 

diets was 0.00 mmol/L (95% CI -0.11 to 0.11). 

Triglycerides - summary of results 

There is no evidence of a difference in triglycerides on diets containing 

oatmeal compared to diets based on refined grains from 

outcome data from pooling of data at 4 weeks, 6 weeks or from 

the pooling of all end-of- study data. 




with the other data for oatmeal, it made no difference to the results. 

Comparison 05 Body weight 

All end-of-study outcomes (Comparison 05, Outcome 01) 

In total, five parallel studies (Johnston 1998; Karmally 2005; 

Keenan 2002; Pins 2002; Reynolds 2000 ) and two crossover studies 

(Leinonen 2000; Pereira 2002) reported body weight at the end 

of the study. All five parallel studies were based on wholegrain oatmeal 

and the crossover studies were on wholegrain rye and a general 

wholegrain diet. In all of the studies the dietary programmes 

were designed to maintain body weight in both the wholegrain 

and control participants. 

On an intra-study basis, three of the parallel studies (oats) reported 

lower final body weight in the wholegrain groups than in the control 

group (Keenan 2002; Pins 2002; Reynolds 2000) and two 

studies reported higher body weight (Johnston 1998; Karmally 

2005). The difference between the groups was significant in only 

one study (Karmally 2005). However, in the paper, a big difference 

between the groups was apparent at baseline so this effect appears 

to be due to poor randomisation. Neither of the two crossover 

studies (rye, general wholegrain diet) reported a significant difference 

in body weight between the wholegrain diets and control 

diets. 

Body weight data was not pooled because there was significant 

heterogeneity (parallel studies on oats, P =0.02, I 2 =64.2%; parallel 

and crossover studies P=0.04. I 2 =54.1%). Graphs are shown for 

information only (Comparison 05, Outcome 01). 

Body weight - summary of results 

There is no evidence of a difference in body weight on diets containing 

oatmeal compared to diets based on refined grains from 

individual studies. Data was not pooled in meta-analysis because 

significant heterogeneity was present. 


wholegrain diets other than oatmeal. Two other studies on other 

wholegrains were found. 

Other outcomes 

Insufficient evidence was found to make any conclusions about 

the effect of wholegrains on any other risk factors for CHD. A 

brief summary of findings is given below. 

Fasting glucose 



Two studies reported fasting glucose outcomes (Pereira 2002; Pins 

2002). In the Pereira study, there was a tendency for fasting glucose 

to be lower with the wholegrain diet (5.2 +/-(SE) 0.08 mmol/L) 

than with the refined grain diet (5.3 +/- (SE) 0.08 mmol/L). 

Keenan reported a significant difference in fasting glucose groups 

(change score). At baseline, the oats group was 118.4 +/- (SE) 

4.1 mg/dL and post treatment 106.1 +/- (SE) 4.2. In the control 

group it was 117.1 +/- (SE) 5.2 at baseline and 119.8 +/- (SE) 5.5 

at post-treatment. 

23

Fasting insulin 

Two studies reported fasting insulin (Keenan 2002; Pereira 2002). 

In the study by Keenan, plasma insulin increased from 12.2 +/- 

(SE) 0.24 uU/mL at baseline in the oats group to 12.8 +/- (SE) 

1.6 post-treatment. In the control group, it was 12.9 +/- (SE) 

2.5 at baseline and 12.9 +/- (SE) 3.2 post-treatment. In the other 

study, fasting insulin was significantly lower during the follow-up 

period with the wholegrain (141 +/- (SE) 3.9 pmol/L) than with 

the refined grain (156 +/-(SE) 3.9 pmol/L) diet, P = 0.03. 

Blood pressure 

Three studies reported blood pressure data (Pins 2002; Reynolds 

2000; Van Horn 1991). In the Van Horn study, systolic blood 

pressure decreased in the oats group from 127.9/80.3 +/- (SD) 

13/10 mmHg to 123.5/77.2 +/- (SD) 14/11. In the control group 

blood pressure also decreased from 129.1/79.1 +/- (SD) 20/8 to 

124.2/77.2 +/- (SD) 13/9. Blood pressure changes were not significant. 

In the other two studies SD data was missing. 

Insulin resistance 

One study reported a homeostasis model for insulin resistance 

which showed that insulin resistance was lower with the wholegrain 

diet (5.4+/-0.18 U) than with the refined grain diet (6.2 +/- 

(SE) 0.18 U) (Pereira 2002). 

Secondary Outcomes 

Of the 10 included studies, six studies reported on side effects 

associated with the consumption of wholegrain foods. The other 

four studies made no comments about side effects. In general, 

there was little difference in side effects between the intervention 

and control groups and no serious side effects. 

Pins (Pins 2002) administered a 42-question side-effect questionnaire 

to participants at the beginning of the baseline phase and at 

the end of the intervention. Participants reported the frequency 

with which they experienced side effects such as flatulence, loose 

stools, headaches, dizziness using a scale of 1 to 5 and values were 

tallied across all 42 questions. A final score was assigned to each 

participant for both time points. Mean scores by group were used 

in the analyses. The oatmeal group had a mean side effects score of 

58.2+/- 7.2 at baseline and a mean score of 47.6+/- 6.9 post-study. 

The control group had a mean side effects score of 56.7 +/- 8.1 at 

baseline and a mean score of 53.4 +/- 7.2 post-study. Side effects 

decreased by 22% in the intervention group and this change was 

significantly different from the change in the control group (at P 

< 0.05). 

Keenan (Keenan 2002) assessed side-effects by a similar method 

to Pins using a 21-question side-effect questionnaire. Mean scores 

by group were used in the analyses. The oatmeal group had a 

mean side effects score of 29.4+/- 3.4 at baseline and a mean score 



of 23.3+/- 3.8 post-study. The control group had a mean side 

effects score of 28.4 +/- 4.3 at baseline and a mean score of 24.9 

+/- 3.7 post-study. There was no statistically significant difference 

between the change in the side effects score in the intervention 

group and the change in the control group (at P < 0.05). 

The study by Pereira (Pereira 2002) included a questionnaire about 

44 side effects using a scale of 1 to 5, including gastrointestinal 

symptoms and general symptoms of acute or chronic illnesses. 

Unusual symptoms were reported more often during the refined 

grain than the wholegrain period and the authors of the study attributed 

the difference to common upper respiratory illnesses in 

two individuals and to chronic low grade abdominal pain in another 

subject. Therefore, the incidence of prescription medication 

was higher with the refined grain than with the wholegrain diet. 

Dry cough (1.4 +/- 0.13 compared with 1.1 +/- 0.13) and sweating 

(1.3 +/- 0.13 compared with 1.0 +/- 0.13) tended to be scored 

higher with the refined grain diet. Bowel movements were more 

frequent with the wholegrain than the refined grain diet (1.8+/- 

0.17 compared with 1.4 +/-0.17 movements/day; P < 0.001). No 

significant differences between treatments were reported for heartburn, 

indigestion, diarrhoea, or loose stools. 

Johnston (Johnston 1998) reported that five out of the total of 124 

participants reported mild gastrointestinal side effects. Three of the 

five were in the placebo group (one reported flatus, two reported 

increased constipation). Of the two participants in the wholegrain 

group who reported gastrointestinal complaints, one reported increased 

flatus and one reported increased stool frequency. 

Reynolds (Reynolds 2000) reported that both the wholegrain oat 

cereal and the control cereal were well tolerated with no serious 

side effects. The non serious adverse reactions reported equally in 

both groups were mild flatus. No further information was given. 

Van Horn (Van Horn 1991) reported that there were no reports 

of side effects by the participants. 

D I S C U S S I O N 

While there is growing evidence from observational studies that 

wholegrains have benefits for coronary heart disease, there is insufficient 

evidence available from randomised controlled trials to 

make any conclusions about wholegrains in general and coronary 

heart disease, except for wholegrain oats. There is some evidence 

from RCTs that wholegrain oats can lower LDL- and total cholesterol 

levels in those with pre-existing risk factors for CHD. This 

effect was seen at 4 weeks for total cholesterol so may be effective 

even with short interventions. However the results of this review 

should be treated with caution because many studies were short 

term, underpowered and funded by companies with commercial 

interests in wholegrains. 

The long-term effects of oats have not been evaluated. Well-designed, 

adequately powered studies are needed to evaluate the ef- 

24

fects of continued consumption of oats. This review found no 

studies on the effect of wholegrains on CHD mortality or events. 

There is also a lack of evidence on outcomes other than lipids. 

This review found a few studies that reported outcomes other than 

lipids such as fasting glucose, fasting insulin, blood pressure and 

insulin resistance but there was not enough evidence to make any 

conclusions about the effect of wholegrains on these outcomes. 

Studies were included in this review if there was a comparison 

between a wholegrain food or diet and a diet or food containing 

no wholegrains or fewer wholegrains. The review did not aim to 

assess the effects of dietary fibre, although the beneficial effects of 

wholegrains may well be associated with the dietary fibre content 

(Brown 1999). For information, the dietary fibre content of the 

foods or diets has been reported in the notes section of the Table of 

Included Studies and is consistently higher in the wholegrain diets 

than the control diets. Many of the studies on oats that have been 

included in the review were aimed at assessing the effect of Betaglucan 

soluble fibre in oatmeal. It has previously been reported 

that the B-glucans in oats can produce a modest reduction in blood 

cholesterol concentration in normocholesterolemic subjects and a 

greater reduction in hypercholesterolemic subjects (Ripsin 1992). 

It is possible that weight loss may account for the observed reductions 

in lipid levels. While weight data has been reported in 

this review, most of the studies had insufficient power to measure 

small changes in weight. Also, studies were only included in the 

review if the only difference in dietary composition was substitution 

of refined grains by wholegrains and therefore the macronutrient 

contents of the diets were similar. However, it is possible that 

small differences in saturated fat intake between the wholegrain 

and control diets may account for the reduction in lipid levels 

found with wholegrain diets. 

There is surprisingly little evidence available from controlled trials 

about the effects of wholegrain foods and diets other than oats and 

there is a need for studies in this area. One observation from this 

References to studies included in this review 

Davidson 1991 {published data only} 

Davidson MH, Dugan LD, Burns JH, Bova J, Story K, Drennan 

KB. The hypocholesterolemic effects of beta-glucan in oatmeal and 

oat bran. JAMA 1991;265(14):1833–9. 

Johnston 1998 {published data only} 

Johnston L, Reynolds HB, Hunninghake DB, Schultz K, 

Westereng B. Cholesterol-lowering benefits of a whole grain oat 

ready to eat cereal. Nutrition Clinical Care 1998;1(1):6–12. 

Karmally 2005 {published data only} 

∗ Karmally W, Montez MG. Cholesterol-lowering benefits of oatcontaining 

cereal in Hispanic Americans. Journal of the American 

Dietetic Association 2005;105(6):967–70. 

R E F E R E N C E S 



review is that there is some inconsistency in the use of the term 

wholegrain. For example, some reviews of wholegrain products 

have included studies on dietary fibre or oatbran and have used the 

term wholegrain interchangeably. There is a need for some clarity 

and consistency in this area. 

A U T H O R S ’ C O N C L U S I O N S 

Implications for practice 

There is some evidence from controlled trials that wholegrain oats 

can reduce LDL cholesterol and total cholesterol risk factors for 

coronary heart disease. However, there is a lack of trials on other 

wholegrain foods and diets. Of the trials that met the review criteria, 

there were many poor quality studies. Many of the trials identified 

were short-term and conducted on small sample sizes. There 

is enough evidence for wholegrain oats to suggest that healthcare 

professionals could recommend oats as part of cholesterol reduction 

programmes. 

Implications for research 

There is a need for well-designed, adequately powered studies to 

evaluate the effect of wholegrains other than oats on coronary heart 

disease and risk factors. There is a need for well designed trials to 

evaluate the long-term effects of oats. There is a need for clarity 

and consistency in the use of the terms wholegrain, bran, germ 

and fibre in published research. 

A C K N O W L E D G E M E N T S 

Margaret Burke, Cochrane Heart Group for advice on the search 

strategy and for assistance with translation of a paper. 

Lone Gale for assistance with translation of a paper. 

Keenan 2002 {published data only} 

Keenan JM, Pins JJ, Frazel C, Moran A, Turnquist L. Oat ingestion 

reduces systolic and diastolic blood pressure in patients with mild 

or borderline hypertension: A pilot trial. The Journal of Family 

Practice (Online) www.jfponline.com 2002;51(4):369. 

Leinonen 2000 {published data only} 

Leinonen KS, Poutanen KS, Mykkanen HM. Rye bread decreases 

serum total and LDL cholesterol in men with moderately elevated 

serum cholesterol. Journal of Nutrition 2000;130:164–70. 

Pereira 2002 {published data only} 

∗ Pereira MA, Jacobs JR, Pins JJ, Raatz SK, Gross MD, Slavin JL, 

Seaquist ER. Effect of whole grains on insulin sensitivity in 

overweight hyperinsulinemic adults. American Journal of Clinical 

25

Nutrition 2002;75:848–55. 

Pins 2002 {published data only} 

Keenan JM, Pins JJ, Geleva D, Frazel C, O’Connor PJ, Cherney 

LM. Whole-grain oat cereal consumption reduces antihypertensive 

medication need: a cost analysis. Preventive Medicine in Managed 

Care 2002;3(1):9–17. 

∗ Pins JJ, Geleva DRD, Keenan JM, Frazel C, O’Connor PJ, 

Cherney LM. Do whole-grain oat cereals reduce the need for 

antihypertensive medications and improve blood pressure control?. 

The Journal of Family Practice 2002;51(4):353–9. 

Reynolds 2000 {published data only} 

Reynolds HR, Quiter E, Hunninghake DB. Whole grain oat cereal 

lowers serum lipids. Topics in Clinical Nutrition 2000;15(4):74–83. 

Van Horn 1988 {published data only} 

Van Horn L, Emidy LA, Liu K, Liao Y, Ballew C, King J, et 

al.Serum lipid response to a fat-modified, oatmeal-enhanced diet. 

Preventive Medicine 1988;17:377–86. 


Van Horn L, Moag-Stahlberg A, Liu K, Ballew C, Ruth K, Hughes 

R, et al.Effects on serum lipids of adding instant oats to usual 

American diets. American Journal of Public Health 1991;81(2): 

183–8. 

References to studies excluded from this review 

Anderson 1978 {published data only} 

Anderson JW, Ward K. Long-term effects of high-carbohydrate, 

high-fiber diets on glucose and lipid metabolism: A preliminary 

report on patients with diabetes. Diabetes Care 1978;1(2):77–82. 

Anderson 1979 {published data only} 

Anderson JW, Ward KW. High-carbohydrate, high-fiber diets for 

insulin-treated men with diabetes mellitus. American Journal of 

Clinical Nutrition. 1979;32:2312–21. 

Asp 1981 {published data only} 

Asp N-G, Agardh C-D, Ahren B, Dencker I, Johansson, C-G, et 

al.Dietary fibre in Type II diabetes. Acta. Med. Scand. 1981;Suppl 

656:47–50. 

Behall 2004a {published data only} 

Behall KM, Scholfield DJ, Hallfrisch J. Diets containing barley 

significantly reduce lipids in mildly hypercholesterolemic men and 

women. American Journal of Clinical Nutrition 2004;80(5): 

1185–93. 

Behall 2004b {published data only} 

Behall KM, Scholfield DJ, Hallfrisch J. Lipids significantly reduced 

by diets containing barley in moderately hypercholesterolemic men. 

Journal of the American College of Nutrition 2004;23(1):55–62. 

Birkeland 1991 {published data only} 

Birkeland KI, Gullestad L, Torsvik H. Cholesterol-lowering effect of 

oats. Tidsskrift for Den Norske Laegeforening 1991;111(17):2081–5. 

Birketvedt 2000 {published data only} 

Birketvedt GS, Auseth J, Florholmen JR, Ryttig K. Long term effect 

of fibre supplement and reduced energy intake on body weight and 

blood lipids in overweight subjects. Acta Medica 2000;43(3): 

129–132. 



Booyens 1966 {published data only} 

Booyens J, De Waal VM, Rademeyer LJ. The effect of dietary maize 

meal supplementation on the levels of serum cholesterol and 

magnesium. South African Medical Journal. 1966;40(11):237–9. 

Bourdon 1999 {published data only} 

Bourdon I, Yokoyama W, Davis P, Hudson C, Backus R, Richter D, 

et al.Postprandial lipid, glucose, insulin, and cholecystokinin 

responses in men fed barley pasta enriched with beta-glucan. 

American Journal of Clinical Nutrition 1999;69:55–63. 

Bruttomesso 1989 {published data only} 

Bruttomesso D, Briani G, Bilardo G, Vitale E, Lavagnini T, 

Marescotti C, et al.The medium-term effect of natural or extractive 

dietary fibres on plasma amino acids and lipids in type 1 diabetics. 

Diabetes Research and Clinical Practice 1989;6:149–55. 

Burr 1989 {published data only} 

Burr ML, Gilbert JF, Holliday RM, Elwood PC, Fehily AM, Rogers 

S, et al.Effects of changes in fat, fish, and fibre intakes on death and 

myocardial reinfarction: Diet and reinfarction trial (DART). Lancet 

1989;2:757–61. 

Cairella 1995 {published data only} 

Cairella G, Cairella M, Marchini G. Effect of dietary fibre on 

weight correction after modified fasting. European Journal of 

Clinical Nutrition 1995;49(Suppl 3):S325–7. 

Chandalia 2000 {published data only} 

Chandalia M, Garg A, Lutjohann D, Von Bergman K, Grundy SM, 

Brinkley LJ. Beneficial effects of high dietary fiber intake in patients 

with type 2 diabetes mellitus. New England Journal of Medicine 

2000;342:1392–8. 

Collier 1982 {published data only} 

Collier G, O’Dea K. Effect of physical form of carbohydrate on the 

postprandial glucose, insulin, and gastric inhibitory responses in 

type 2 diabetes. American Journal of Clinical Nutrition 1982;36: 

10–14. 

Comi 1995 {published data only} 

Comi D, Brugnani M, Gianino A. Metabolic effects of hypocaloric 

high-carbohydrate/high-fibre diet in non-insulin dependent 

diabetic patients. European Journal of Clinical Nutrition 1995;49 

(Suppl 3):S242–4. 

Crapo 1981 {published data only} 

Crapo PA, Insel J, Sperling M, Kolterman OG. Comparison of 

serum glucose, insulin, and glucagon responses to different types of 

complex carbohydrate in noninsulin-dependent diabetic patients. 


Data 1980 {published data only} 

Data PG, Cacchio M, Sergiacomo P, Di Tano G. Investigation of 

the importance of dietetic fibers in the regulation of 

cholesterolemia. Bollettino della Societa Italiana di Biologia 

Sperimentale 1980;16:1545–50. 

Davy 2002a {published data only} 

Davy BM, Melby CL, Beske SD, Ho RC, Davrath LR, Davy KP. 

Oat consumption does not affect resting casual and ambulatory 24h 

arterial blood pressure in men with high-normal blood pressure to 

stage I hypertension. Journal of Nutrition. 2002;132(3):394–8. 

26

Davy 2002b {published data only} 

Davy BM, Davy KP, Ho RC, Beske SD, Davrath LR, Melby CL. 

High-fiber oat cereal compared with wheat cereal consumption 

favorably alters LDL-cholesterol subclass and particle numbers in 

middle-aged and older men. American Journal of Clinical Nutrition 

2002;76:351–8. 

Eliasson 1992 {published data only} 

Eliasson K, Ryttig KR, Hylander B, Rossner S. A dietary fibre 

supplement in the treatment of mild hypertension. A randomized, 

double-blind, placebo-controlled trial. Journal of Hypertension 

1992;10:195–9. 

Fehily 1986 {published data only} 

Fehily AM, Burr M, Butland BK, Eastham RD. A randomised 

controlled trial to investigate the effect of a high fibre diet on blood 

pressure and plasma fibrinogen. Journal of Epidemiology & 

Community Health. 1986;40:334–7. 

Fischer 2000 {published data only} 

Fischer J. Fiber-rich food improves the day-time blood glucose 

profile in patients with overweight and diabetes mellitus type 2. 

Schweizerische Rundschau fur Medizin Praxis 2000;89:1975–6. 

Fordyce-Baum 1989 {published data only} 

Fordyce-Baum MK, Langer L, Mantero-Atienza E, Crass R, Beach 

RS. Use of an expanded whole-wheat product in the reduction of 

body weight and serum lipids in obese females. American Journal of 

Clinical Nutrition 1989;50(1):30–6. 

Fraser 1981 {published data only} 

Fraser GE, Jacobs DR, Anderson JT, Foster N, Palta M, Blackburn 

H. The effect of various vegetable supplements on serum 

cholesterol. American Journal of Clinical Nutrition 1981;34: 

1272–7. 

Fung 2002 {published data only} 

Fung TT, Hu FB, Pereira MA, Liu S, Stampfer MJ, Colditz GA, et 

al.Whole-grain intake and the risk of type 2 diabetes: A prospective 

study in men. American Journal of Clinical Nutrition 2002;76: 

535–40. 

Golay 1992 {published data only} 

Golay A, Koellreutter B, Bloise D, Assal J-P, Wursch P. The effect of 

muesli or cornflakes at breakfast on carbohydrate metabolism in 

type 2 diabetic patients. Diabetes Research & Clinical Practice. 

1992;15:135–42. 

Guzic 1994 {published data only} 

Guzic B, Sundell IB, Keber I, Keber D. The effect of oat husk 

supplementation in diet on plasminogen activator inhibitor type 1 

in diabetic survivors of myocardial infarction. Fibrinolysis 1994;8 

(Suppl 2):44–6. 

Hagander 1985 {published data only} 

Hagander B, Bjorck I, Asp N-G, Lunquist I, Nilsson-Ehle P, 

Schrezenmeir J, et al.Hormonal and metabolic responses to 

breakfast meals in NIDDM: Comparison of white and whole-grain 

wheat bread and corresponding extruded products. Human 

Nutrition Applied Nutrition 1985;39A:114–23. 

Hagander 1988 {published data only} 

Hagander B, Asp N-G, Efendic S, Nilsson-Ehle P, Schersten B. 

Dietary fiber decreases fasting blood glucose levels and plasma LDL 

concentration in non-insulin-dependent diabetes mellitus patients. 




He 1995 {published data only} 

He J, Klag MJ, Whelton PK, Mo J-P, Qian M-C, Mo P-S, et 

al.Oats and buckwheat intakes and cardiovascular disease risk 

factors in an ethnic minority of China. American Journal of Clinical 

Nutrition 1995;61:366–72. 

Heaton 1976 {published data only} 

Heaton KW, Manning AP, Hartog M. Lack of effect on blood lipid 

and calcium concentrations of young men on changing from white 

to wholemeal bread. British Journal of Nutrition. 1976;35:55–60. 

Hoffman 1982 {published data only} 

Hoffman CR, Fineberg SE, Howey DC, Clark CM, Pronsky Z. 

Short-term effects of a high-fiber, high carbohydrate diet in very 

obese diabetic individuals. Diabetes Care 1982;5(6):605–11. 

Hollenbeck 1986 {published data only} 

Hollenbeck CB, Coulston AM, Reaven GM. To what extent does 

increased dietary fiber improve glucose and lipid metabolism in 

patients with noninsulin-dependent diabetes mellitus (NIDDM)?. 

American Journal of Clinical Nutrition. 1986;43:16–24. 

Hunninghake 1994 {published data only} 

Hunninghake DB, Miller VT, LaRosa JC, Kinosian B, Brown V, 

Howard WJ, et al.Hypocholesterolemic effects of a dietary fiber 

supplement. American Journal of Clinical Nutrition. 1994;59: 

1050–4. 

Jacobs 2002 {published data only} 

Jacobs DR, Pereira MA, Stumpf K, Pins JJ, Adlercreutz H. Whole 

grain food intake elevates serum enterolactone. British Journal of 

Nutrition 2002;88:111–6. 

Jang 2001 {published data only} 

Jang Y, Lee JH, Kim OY, Park HY, Lee SY. Consumption of whole 

grain and legume powder reduces insulin demand, lipid 

peroxidation, and plasma homocysteine concentrations in patients 

with coronary artery disease: Randomized controlled clinical trial. 

Arteriosclerosis Thrombosis & Vascular Biology 2001;21:2065–71. 

Jenkins 1985 {published data only} 

Jenkins DJA, Wolever TMS, Kalmusky J, Giudici S, Giordano C, 

Wong GS, et al.Low glycemic index carbohydrate foods in the 

management of hyperlipidemia. American Journal of Clinical 

Nutrition 1985;42:604–17. 

Jenkins 1993 {published data only} 

Jenkins D, Wolever T, Rao V, Hegele RA, Mitchell SJ, Ransom T, 

et al.Effect on blood lipids of very high intakes of fiber in diets low 

in saturated fat and cholesterol. New England Journal of Medicine 

1993;329:21–6. 

Judd 1981 {published data only} 

Judd PA, Truswell AS. The effect of rolled oats on blood lipids and 

fecal steroid excretion in man. American Journal of Clinical 

Nutrition 1981;34:2061–7. 

Juntunen 2002 {published data only} 

Juntunen KS, Niskanen LK, Liukkonen KH, Poutanen KS, Holst 

JJ, Mykkanen HM. Postprandial glucose, insulin, and incretin 

responses to grain products in healthy subjects. American Journal of 

Clinical Nutrition 2002;75:254–62. 

Juntunen 2003 {published data only} 

Juntunen KS, Laaksonen DE, Poutanen KS, Niskanen LK, 

Mykkanen HM. High-fiber rye bread and insulin secretion and 

27

sensitivity in healthy menopausal women. American Journal of 


Kabir 2002 {published data only} 

Kabir M, Oppert J-M, Vidal H, Bruzzo F, Fiquet C, Wursch P, 

Slama G, Rizkalla SW. Four-week low-glycemic index breakfast 

with a modest amount of soluble fibers in type 2 diabetic men. 

Metabolism: Clinical & Experimental 2002;51(7):819–26. 

Karlstrom 1984 {published data only} 

Kalstrom B, Vessby B, Asp N-G, Boberg M, Gustafsson I-B, Lithell 

H, et al.Effects of increased content of cereal fibre in the diet of 

Type 2 (non-insulin-dependent) diabetic patients. Diabetologia 

1984;26:272–7. 

Katz 2001a {published data only} 

Katz DL, Nawaz H, Boukhalil J, Chan W, Ahmadi R, Giannamore 

V, et al.Effects of oat and wheat cereals on endothelial responses. 

Preventive Medicine. 2001;33:476–84. 

Katz 2001b {published data only} 

Katz DL, Nawaz H, Boukhalil J, Giannamore V, Chan W, Ahmadi 

R, et al.Acute effects of oats and vitamin E on endothelial responses 

to ingested fat. American Journal of Preventive Medicine 2001;20(2): 

124–9. 

Kay 1977 {published data only} 

Kay RM, Truswell AS. The effect of wheat fibre on plasma lipids 

and faecal steroid excretion in man. British Journal of Nutrition 

1977;37:227–35. 

Kay 1981 {published data only} 

Kay RM, Grobin W, Track NS. Diets rich in natural fibre improve 

carbohydrate tolerance in maturity-onset, non-insulin dependent 

diabetics. Diabetologia 1981;20:18–21. 

Kesaniemi 1990 {published data only} 

Kesaniemi YA, Tarpila S, Miettinen TA. Low vs high dietary fiber 

and serum, biliary, and fecal lipids in middle-aged men. American 

Journal of Clinical Nutrition. 1990;51:1007–12. 

Kleemola 1999 {published data only} 

Kleemola P, Puska P, Vartiainnen, Roos E, Luoto R, Ehnholm C. 

The effect of breakfast cereal on diet and serum cholesterol: A 

randomized trial in North Karelia, Finland. European Journal of 


Kris-Etherton 2002 {published data only} 

Kris-Etherton PM, Shaffer-Taylor D, Smicklas-Wright H, Mitchell 

DC, Bekhuis TC, Olson BH, et al.High-soluble-fiber foods in 

conjunction with a telephone-based, personalized behavior change 

support service result in favorable changes in lipids and lifestyles 

after 7 weeks. Journal of the American Dietetic Association. 2001; 

102:503–10. 

Lakshmi 1996 {published data only} 

Lakshmi KB, Vimala V. Hypoglycemic effect of selected sorghum 

recipes. Nutrition Research 1996;16(10):1651–58. 

Leinonen 1999 {published data only} 

Leinonen K, Liukkonen K, Poutanene K, Uusitupa M, Mykkanen 

H. Rye bread decreases postprandial insulin response but does not 

alter glucose response in healthy Finnish subjects. European Journal 

of Clinical Nutrition 1999;53(4):262–7. 



Liese 2003 {published data only} 

Liese AD, Roach AK, Sparks KC, Marquart L, D’Agostino RB, 

Mayer-Davis E. Whole-grain intake and insulin sensitivity: the 

Insulin Resistance Atherosclerosis Study. American Journal of 

Clinical Nutrition 2003;78(5):965–71. 

Lousley 1984 {published data only} 

Lousley SE, Jones DB, Slaughter P, Carter RD, Jelfs R, Mann JI. 

High carbohydrate-high fibre diets in poorly controlled diabetes. 

Diabetic Medicine 1984;1(1):21–5. 

MacMahon 1998 {published data only} 

Macmahon M, Carless J. Ispaghula husk in the treatment of 

hypercholesterolaemia: a double blind controlled study. Journal of 

Cardiovascular Risk 1998;5(3):167–72. 

Manhire 1981 {published data only} 

Manhire A, Henry CL, Hartog M, Heaton KW. Unrefined 

carbohydrate and dietary fibre in treatment of diabetes mellitus. 

Journal of Human Nutrition 1981;35:99–101. 

Mathur 1968 {published data only} 

Mathur KS, Khan MA, Sharma RD. Hypocholesterolaemic effect 

of Bengal gram: a long-term study in man. British Medical Journal. 

1968;1:30–1. 

McIntosh 1991 {published data only} 

McIntosh GH, Whyte J, McArthur R, Nestel PJ. Barley and wheat 

foods: influence on plasma cholesterol concentrations in 

hypercholesterolemic men. American Journal of Clinical Nutrition 

1991;53:1205–9. 

Montonen 2003 {published data only} 

Montonen J, Knekt P, Jarvinen R, Aromaa A, Reunanen A. Wholegrain 

and fiber intake and the incidence of type 2 diabetes. 


Nielsen 1988 {published data only} 

Nielsen GL, Thuesen H. Blood glucose responses to sweetcorn and 

potato meals. Diabetic Medicine 1988;5(6):598–9. 

O’Kell 1988 {published data only} 

O’Kell RT, Duston AA. Lack of effect of dietary oats on serum 

cholesterol. Missouri Medicine 1988;85(11):726–8. 

Odes 1993 {published data only} 

Odes HS, Lazovski H, Stern I, Madar Z. Double-blind trial of a 

high dietary fiber, mixed grain cereal in patients with chronic 

constipation and hyperlipidemia. Nutrition Research 1993;13: 

979–85. 

Pacy 1986 {published data only} 

Pacy PJ, Dodson PM, Taylor MP. The effect of a high fibre, low fat, 

low sodium diet on diabetics with intermittent claudication. British 

Journal of Clinical Practice 1986;40(8):313–7. 

Poulter 1993 {published data only} 

Poulter N, Chang CL, Cuff A, Poulter C, Sever P, Thom S. Lipid 

profiles after the daily consumption of an oat-based cereal: a 

controlled crossover trial. American Journal of Clinical Nutrition 

1993;58:66–9. 

Reynolds 1989 {published data only} 

Reynolds HR, Lindeke E, Hunninghake DB. Effect of oat bran on 

serum lipids. Journal of the American Dietetic Association 1989;89 

(Suppl):A112. 

28

Rigaud 1990 {published data only} 

Rigaud D, Ryttig KR, Angel LA, Apfelbaum M. Overweight 

treated with energy restriction and a dietary fibre supplement: a 6month 

randomized, double-blind, placebo-controlled trial. 

International Journal of Obesity. 1990;14:763–9. 

Roth 1985 {published data only} 

Roth G, Leitzmann C. Long-term influence of breakfast cereals rich 

in dietary fibres on human blood lipid values [Langzeieinfluss 

ballast–stoffreicher Fruhstuck–cerealien auf die Blutlipide beim 

Menschen]. Aktuelle Ernahringsmedizin Klinik und Praxis 1985;10 

(3):106–9. 

Russ 1985 {published data only} 

Russ CS, Atkinson RL. Use of high fiber diets for the outpatient 

treatment of obesity. Nutrition Reports International 1985;32(1): 

193–8. 

Rytter 1996 {published data only} 

Rytter E, Erlanson-Albertsson C, Lindahl L, Lundquist I, Viberg U, 

Akesson B, et al.Changes in plasma insulin, enterostatin, and 

lipoprotein levels during an energy-restricted dietary regimen 

including a new oat-based liquid food. Annals of Nutrition & 

Metabolism. 1996;40:212–20. 

Saltzman 2001a {published data only} 

Saltzman E, Moriguti JC, Das SK, Corrales A, Fuss P, Greenberg 

AS, et al.Effects of a cereal rich in soluble fiber on body composition 

and dietary compliance during consumption of a hypocaloric diet. 

Journal of the American College of Nutrition 2001;20(1):50–7. 

Saltzman 2001b {published data only} 

Saltzman E, Das SK, Lichtenstein AH, Dallal GE, Corrales A, 

Schaefer EJ, et al.An oat-containing hypocaloric diet reduces 

systolic blood pressure and improves lipid profile beyond effects of 

weight loss in men and women. Journal of Nutrition. 2001;131: 

1465–70. 

Schlamowitz 1987 {published data only} 

Schlamowitz P, Halberg T, Warnoe O, Wilstrup F, Ryttig K. 

Treatment of mild to moderate hypertension with dietary fibre. 

Lancet. 1987;2:622–3. 

Turnbull 1987 {published data only} 

Turnbull WH, Leeds AR. Reduction of total and LDL-C 

cholesterol in plasma by oats. Journal of Clinical Nutrition 

Gastroenterology 1987;2:177–81. 

Turnbull 1989 {published data only} 

Turnbull WH, Leeds AR. The effect of rolled oats and a reduced/ 

modified fat diet on apolipoproteins A1 and B. J Clin Nutr 

Gastroenterol 1989;1:15–19. 

Turpeinen 2000 {published data only} 

Turpeinen AM, Juntunen K, Mutanen M, Mykkanen H. Similar 

responses in hemostatic factors after consumption of wholemeal rye 

bread and low-fiber wheat bread. European Journal of Clinical 

Nutrition 2000;54:418–23. 


Van Horn LV, Liu K, Parker D, Emidy L, Liao Y, Pan WH, et 

al.Serum lipid response to oat product intake with a fat-modified 

diet. Journal of the American Dietetic Association 1986;86(6): 

759–64. 




Van Horn L, Liu K, Gerber J, Garside D, Schiffer L, Gernhofer N, 

et al.Oats and soy in lipid-lowering diets for women with 

hypercholesterolemia: is there synergy?. Journal of the American 

Dietetic Association. 2001;101:1319–1325. 

Willms 1987 {published data only} 

Willms B, Arends J. Comparison of isolated (guar) and natural 

(Musli) dietary fiber in the treatment of type II diabetes [Verglech 

von isolierten (Guar) und naturlichen (Musli) Ballastoffen in der 

therapie des Typ–II–Diabetes]. Medizinische Klinik. 1987;12/13: 

429–31. 

Wolever 2003 {published data only} 

Wolever TMS, Tshilias EB, McBurney MI, Le N-A. Long-term 

effect of reduced carbohydrate or increased fiber intake on LDL 

particle size and HDL composition in subjects with type 2 diabetes. 

Nutrition Research 2003;23:15–26. 

Wolffenbuttel 1992 {published data only} 

Wolffenbuttel BHR, Sels J-PJE, Heesen BJ, Menheere PPCA, 

Nieuwenhuijzen-Kruseman AC. The effects of dietary fibre and 

insulin treatment on the serum levels of lipids and lipoprotein (a) in 

patients with diabetes mellitus type II. Nederlands Tijdschrift voor 

Geneeskunde 1992;136(15):739–42. 

Wursch 1991 {published data only} 

Wursch P, Koellreutter B, Haesler E, Felber JP, Golay A. Metabolic 

effects of slow release starch in non-insulin dependent diabetic 

patients. Diabetes, Nutrition & Metabolism 1991;4(3):195–9. 

References to ongoing studies 

FSA 2005a {unpublished data only} 

Food Standards Agency. FSA research project list. Available at: 

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FSA 2005b {unpublished data only} 

Food Standards Agency. FSA research projects list. Available at: 

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408–12. 

Seal 2006 

Seal CJ. Wholegrains and CVD risk. Proceedings of the Nutrition 

Society 2006;65:1–12. 

Slavin 2001 

Slavin JL, Jacobs D, Marquart L, Wiemer K. The role of whole 

grains in disease prevention. Journal of the American Dietetic 

Association 2001;101:780–5. 

Slavin 2003 

Slavin J. Why wholegrains are protective: biological mechanisms. 

Proceedings of the Nutrition Society 2003;62:129–34. 

Steffen 2003 

Steffen LM, Jacobs DR, Stevens J, Shahar E, Carithers T, Folsom A. 

Associations of whole-grain, refined grain, and fruit and vegetable 

consumption with risks of all-cause mortality and incident coronary 

artery disease and ischemic stroke: the Atherosclerosis Risk in 

Communities (ARIC) study. American Journal of Clinical Nutrition 

2003;78:383–90. 

Wolk 1999 

Wolk A, Manson JE, Stampfer MJ, Colditz GA. Long-term intake 

of dietary fiber and increased risk of coronary heart disease among 

women. JAMA 1999;281:1998–2004. 

∗ Indicates the major publication for the study 

30

C H A R A C T E R I S T I C S O F S T U D I E S 

Characteristics of included studies [ordered by study ID] 

Davidson 1991 

Methods Study design: Randomised parallel study. 

Random allocation: Unclear. 

Allocation concealment: Unclear. 

Blinding of outcome assessors: Unclear - reported to be a single-blind study but not clear who was blinded. 

Length of intervention: 6 weeks. 

Unit of allocation: Participant. 

Unit of analysis: Participant. 

Protection against contamination: Unclear. 

Intention-to-treat analysis: Reported but inadequate (only 148 of 156 patients randomised included in 

ITT analysis). 

Participants Diagnosis of CHD or risk factors: Hypercholesterolemic: LDL cholesterol >4.14 mmol/L or between 3.37 

and 4.14 mmol/L with multiple risk factors. 

Exclusion criteria: LDL cholesterol outwith the above values, women who were pregnant or lactating, 

subjects weighing more than 150% of their ideal body weight or with serious metabolic disorders, including 

alcoholism and diabetes. 

Medications used: No lipid-lowering medication used for 6 weeks prior to trial. 

Smoking status: Not reported. 

n = 156 randomised to 7 groups, 148 completed. For this review only those in the OM-28 oatmeal group 

have been included: OM-28 n = 20 (baseline and follow-up); control: n = 15 (baseline and follow-up) 

Mean age: 51.1 years (no SD). 

Male/female ratio: 7/13 

Baseline characteristics: Reported. 

Geographical location: USA. 

Interventions Intervention: This study was a dose-response study but only the OM-28 group (28g oatmeal group) has 

been included in meta-analysis for this review as a direct w/w comparison with the control. 

The intervention was a low fat, low cholesterol diet plus 28 g of dry oatmeal daily consumed as hot cereal, 

muffins or shakes as a substitute for matching servings of complex carbohydrates in the diet. (8 week runin 

on low-fat, low cholesterol diet only prior to intervention). 

Control: Low fat, low cholesterol diet as above replacing oatmeal with 28g of dry farina placebo. 

Assessment of dietary compliance: 4-day food records 

Comparison of total energy and macronutrient intakes: Reported 

Outcomes Main outcomes: Total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides 

Other outcomes: None 

Notes Dietary fibre intake - the study reports that a significant group difference and a time-by group interaction 

were detected for total dietary fibre, insoluble fibre and water-soluble fibre. This study was a dose response 

study and reports that the differences were expected and proportionally responded to the supplementation 

of oat cereal and beta-glucan. However, no specific information as to whether differences in fibre content 

were significant between the OM-28 group and control. 

Risk of bias 



31

Davidson 1991 (Continued) 

Item Authors’ judgement Description 

Allocation concealment? Unclear B - Unclear 

Johnston 1998 




Blinding of outcome assessors: Unclear. 

Blinding of participants and cereal dispensers may have been done but unclear from published details. 

Study participants and the providers of the cereals were blinded. 



Unit of analysis: Participant 

Protection against contamination: Unclear 

Intention-to-treat analysis: Not done 

Participants Diagnosis of CHD or risk factors: Mild to moderate primary hypercholesterolemia. LDL cholesterol 3.37 

- 4.9 mmol/L prior to study. 

Exclusion criteria: LDL cholesterol outwith the above values; participants outwith 40-70 years old; baseline 

triglycerides >3.39 mmol/L; body weight > 140% of ideal; history of major surgery in the previous 3 

months; clinically significant metabolic, renal, hepatic, gastrointestinal, pulmonary, hemapoietic, thyroid 

or cardiovascular diseases; history of allergic reactions to corn, wheat, oats or rice products; subjects taking 

certain corticosteroids, androgens or lipid-lowering drugs. 

Medications used: Subjects taking some drugs potentially affecting lipids i.e. estrogen, estrogen/progestin, 

thiazide diuretics, beta blockers and thyroid hormones were allowed as long as they were on stable doses. 

Smoking status: Remained constant throughout the study n = 135 randomised to 2 groups, 124 completed. 

Control group: n = 62 baseline, n = 62 end. Intervention group (Cheerios): n = 62 baseline, n = 62 end. 

Mean age: control group 57.3 years (no SD); intervention group 56.7 years. 

Male/female ratio: 38/24 (control); 40/22 (intervention). 



Interventions Intervention: Wholegrain ready-to-eat cereal (Cheerios) composed of wholegrain oat flour 3 ounces daily 

as part of ’Step One’ diet (6 week run-in on ’Step One’ diet prior to intervention). 

Control: Commercial cornflakes 3 ounces daily as part of ’Step One’ diet. 

Assessment of dietary compliance: subject interviews, daily log of cereal intake, counting returned unopened 

boxes of cereal. 

Comparison of total energy and macronutrient intakes: Reported. 

Outcomes Main outcomes: Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, body weight. 

Other outcomes: Apo A-1, Apo B, participants report of adverse reactions. 

Notes Dietary fibre intake - the study reports that minor but statistically significant differences between control 

and treatment groups were detected for posttreatment intake of total dietary fibre (20.2 g control; 24.8 g 

treatment P

Johnston 1998 (Continued) 

Risk of bias 



Karmally 2005 









Intention-to-treat analysis: Unclear. 

Participants Diagnosis of CHD or risk factors: Mild to moderate primary hypercholesterolemia. LDL-cholesterol 3.1 

to 4.9 mmol/L prior to study and triglycerides < 4.52 mmol/L. 

Exclusion criteria: LDL cholesterol outwith the above values; participants outwith 30-70 years old; baseline 

triglycerides >4.52 mmol/L; body mass index > 38, history of heart disease, stroke, liver disease, abnormal 

blood count and renal function, use of lipid-lowering drugs/ botanicals/corticosteroids, androgens and 

food allergies. Medication was allowed if subjects were on stable doses of estrogen, estrogen/progestin, 

thiazide, beta-blockers and thyroid hormones. 

Smoking status: Unclear 

n = 152 randomised to 4 groups, 146 completed. Two arms for each intervention group for each location 

i.e. Columbia University(CU)/University of Texas (UoT). In total 79 in corn cereal group (39 CU/40 

UoT); in total 73 in oat-group (35 UC/ 38 UoT). 

Mean age: Corn group: CU 46.3+/- 9.7; UoT 51.5+/- 10.5. Oat group: CU 48.4+/- 11.9; UoT 49.7+/- 

10.5 years. 

Male/female ratio: Corn group: CU 9/3; UoT 12 /28. Oat group: CU 14/21; UoT 14/24. 



Interventions Intervention: 45g of wholegrain ready to eat oat cereal (Cheerios) as part of National Cholesterol Education 

Program (NCEP) ’Step One’ diet. 

Control: 45 ounces of corn cereal daily as part of ’Step One’ diet. Both groups ate the NCEP ’Step One’ 

diet for 5 weeks before intervention. 

Assessment of dietary compliance: 3 day food records and unannounced telephone calls for 24 hour recalls. 

Compliance with cereal consumption was determined from the number of unopened and empty packages 

at each visit, daily cereal intake records and participant interviews. 


Outcomes Main outcomes: Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, body weight. 




33

Karmally 2005 (Continued) 

Notes Dietary fibre intake - the study reports that the wholegrain oat cereal provided 3.0 g of soluble fibre daily 

and the control cereal contained no soluble fibre. There was no difference in the soluble fibre content of 

the background ’Step One’ diets in the two groups. 

Risk of bias 



Keenan 2002 




Blinding of outcome assessors: Done for blood pressure but not clear if done for lipids. 





Intention-to-treat analysis: Not done. 

Participants Diagnosis of CHD or risk factors: Hypertensives with average SBP of 130 to 160 mmHg and DBP of 85 

to 100 mmHg and with at least one reading greater than 140/190 as well as moderately elevated levels of 

fasting insulin (>10 µU/mL). 

Exclusion criteria: SBP, DBP and fasting insulin outwith the specified levels for inclusion. History of 

complications of hypertension, intestinal surgery or gastrointestinal diseases, chronic use of medications 

affecting the gastrointestinal tract, excessive alcohol use, smoking, diabetes, obesity, high soluble fibre diet, 

estrogen replacement therapy dosage unstable or greater than 2mg. Medications used: Not reported. 

Smoking status: Smokers excluded. 

n = 22 randomised to 2 groups, 18 completed. 

Treatment n=10 (baseline and follow-up); control: n=8 (baseline and follow-up) 

Mean age: 44 years (SD 18) 

Male/female ratio: 50% M/50% F in both groups. 

Baseline characteristics: Reported 

Geographical location: USA 

Interventions Intervention: Whole oat cereal. 

Control: Low fibre cereal (type not specified). 

Assessment of dietary compliance: Self-report in a daily cereal calendar, 3-day food records at baseline and 

at 6 weeks. 


Outcomes Main outcomes: Systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, HDL 

cholesterol, LDL cholesterol, body weight, fasting insulin. 




34

Keenan 2002 (Continued) 

Notes Dietary fibre intake - the study reports that the treatment oat cereal was standardised to 5.52 g/day betaglucan 

and to a low fibre cereal control (less than 1.0 g/day total fibre). 

Risk of bias 



Leinonen 2000 

Methods Study design: Randomised crossover study. 








Intention-to-treat analysis: Not done formally but all 40 subjects randomised appear to have completed 

the study. 

Participants Diagnosis of CHD or risk factors: Elevated serum cholesterol concentrations. Total serum cholesterol 5.5 

- 7.5 mmol/L. 

Exclusion criteria: Serum total cholesterol outwith above values; serum total triglycerides > 2.5 mmol/L, 

body mass index outwith 20-32; subjects taking lipid-lowering medication. Medications used: None 

reported other than those on lipid-lowering medication were excluded. 


n = 40 randomised (crossover), 40 completed. 

Mean age: men 43+/- 2.0 years (SEM); women 43 +/- 1.6 years (SEM) 


Baseline characteristics: Reported 

Geographical location: Finland 

Interventions Intervention: Wholemeal rye bread based on finely milled wholemeal rye flour replaced customarily used 

breads and baked products in the usual diet. 

Control: Wheat breads made from refined wheat flour replaced customarily used breads and baked products 

in the usual diet. 

Washout interval (for crossover studies): 4 weeks. 

Assessment of dietary compliance: Daily records and 4-day food records. 


Outcomes Main outcomes: Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, body weight 

Other outcomes: Values not reported but no significant changes were found in the fasting plasma glucose 

and insulin concentrations during the study. 



35

Leinonen 2000 (Continued) 

Notes Dietary fibre intake - the study reports significant differences for both men and women between the 

wholemeal rye bread and refined wheat bread for total dietary fibre, soluble fibre and insoluble fibre (P < 

0.05). 

Risk of bias 



Pereira 2002 

Methods Study design: Randomised crossover study. 









Participants Diagnosis of CHD or risk factors: overweight and obese adults with hyperinsulinaemia. 

Exclusion criteria: outwith age 21-65 years; body mass index outwith 26-36; body weight fluctuation over 

past 6 months > 10%; smoking; consumption > 2 alcoholic drinks/day; diagnosed with diabetes, cancer 

CVD or other chronic medical conditions; those taking medications that would affect glucose, insulin, 

lipids or blood pressure; those engaging in a high level of physical activity; those following a special diet; 

those allergic to any foods. 

Medications used: None of the participants were taking medications that would affect glucose, insulin, 

lipids or blood pressure. 

Smoking status: Smokers excluded from study. 

n = 12 randomised (crossover), 11 completed. 

Mean age: 41.6+/- 2.67 years (SEM). 




Interventions Intervention: Wholegrain diet including 6-10 servings daily of wholegrain breakfast cereal, bread, rice, 

pasta, muffins, cookies and snacks of which approx. 80% were wheat and the remainder oats, rice, corn, 

barley, rye on a 6-day menu rotation. 

Control: As above but 6-10 servings of refined grain foods daily instead of wholegrain foods based on 

white bread and refined wheat, rice and corn products. 

Washout interval (for crossover studies) : 6-9 weeks. 

Assessment of dietary compliance: Daily records and all food provided to participants. All participants 

were renumerated on completion of the study. 




36

Pereira 2002 (Continued) 

Outcomes Main outcomes: Fasting insulin, fasting glucose, insulin sensitivity (insulin clamp), body weight. 

Other outcomes: Side effects reported by participants 

Notes Dietary fibre intake - the study reports higher intakes of dietary fibre in the wholegrain group than 

the refined grain group for total dietary fibre (28.0 g wholegrain; 17.8 g control); soluble fibre (7.7 g 

wholegrain; 6.7 g control) and insoluble fibre (19.7 g wholegrain; 10.8 g control) but does not report 

whether the differences were statistically significant. 

Risk of bias 



Pins 2002 




Blinding of outcome assessors: Done . 

The cereal dispenser was also blinded. 





Intention-to-treat analysis: Not done formally but all 88 subjects randomised appear to have completed 

the study. 

Participants Diagnosis of CHD or risk factors: Mild or moderate hypertension. 

Exclusion criteria: History of systolic BP >160mmHg or diastolic BP > 115 mmHg; existing complications 

of hypertension; history of major intestinal surgeries; malabsorption of the gastrointestinal tract or biliary 

disease; use of beta-blockers; diabetes mellitus; body mass index > 35; history of excessive use of alcohol; 

current smoking; high soluble fibre intake; clinical use of antacids, bulk laxatives or other medications 

affecting gastrointestinal tract; continuous treatment with estrogen replacements, participation in another 

study 3 months before randomisation. 

Medications used: No more than one anti-hypertensive medication and/or one diuretic medication. 80 

participants were on a single anti-hypertensive medication, 8 were on an anti-hypertensive drug plus a 

diuretic medication. 

Smoking status: No smokers included. 

n = 88 randomised to 2 groups, 88 completed. 

Control group: n = 43 baseline, n = 43 end. Intervention group: (Cheerios) n = 45 baseline, n = 45end. 

Mean age: Control group 46.4 years (+/- 15.3 SD); Intervention group 48.7 years (+/- 16.9 SD) 






37

Pins 2002 (Continued) 

Interventions Intervention: Whole oat cereals (oatmeal and oat squares) as part of usual diet. 

Control: Refined grain wheat-based cereals (hot wheat cereal and Kellogg’s Crispix) as part of usual diet. 

Assessment of dietary compliance: 3-day food records at baseline and end of 12 weeks, and cereal diaries 

kept. 


Outcomes Main outcomes: Total cholesterol, LDL cholesterol, triglycerides, bodyweight. 

Other outcomes: Proportion of participants reducing anti-hypertensive medication (no SD/SEM), mean 

blood pressure (no SD/SEM), plasma glucose (not clear if this is fasting glucose) 

Notes Dietary fibre intake - **still awaiting table W1 from full paper**. 

Risk of bias 



Reynolds 2000 



Allocation concealment: Done. 

Blinding of outcome assessors: Not clear. 






Participants Diagnosis of CHD or risk factors: mild to moderate hypercholesterolemia (mean baseline value 5.94+/- 

0.65 mmol/L). 

Exclusion criteria: Baseline triglyceride > 3.39 mmol/L; body weight > 30% over ideal; history of recent 

myocardial infarction; major surgery; unstable angina; congestive heart failure; significant metabolic, renal, 

hepatic or gastrointestinal disease; concurrent use of corticosteroids, thiazides, estrogens, progesterones, 

antibiotics or lipid-lowering agents. 

Medications used: Beta-adrenergic blockers were allowed if dose was kept constant during the study. 

Smoking status: Smokers included but proportion not reported. 

n = 46 randomised. Participants were paired by gender and cholesterol levels before randomisation, 43 

completed. Whole oat cereal treatment group n = 22 (baseline and follow-up); Control: n = 21 (baseline 

and follow-up). 

Mean age: 51.6 years (no SD). 






38

Reynolds 2000 (Continued) 

Interventions Intervention: American Heart Association (AHA) ’Step One’ diet plus 2 portions of 42.5g wholegrain oat 

puffs daily. 

Control: AHA ’Step One’ diet plus two portions of 42.5g commercial cornflakes daily. 

Assessment of dietary compliance: Subject interviews, counting returned unopened boxes of cereal. 


Outcomes Main outcomes: Total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, blood pressure, bodyweight. 

Notes Dietary fibre intake - the study reports that differences between control and treatment groups were detected 

for mean posttreatment intake of total dietary fibre (16.8+/-1.1 g control; 25.5 +/- 1.5 g treatment P 

< 0.001); posttreatment soluble fibre intake (5.2 +/- 0.3 g control; 8.8+/-0.4 g whole oat treatment P 

198 mg/dL (5.12 mmol/L) 

Exclusion criteria: Those taking lipid-lowering medication, pregnancy, more than 1.5 times desirable 

weight for height. 

Medications used: No lipid-lowering medication used. 


For subgroup with total cholesterol > 198 mg/dL number randomised not reported. Results reported for 

118 who completed. Control group: n = 59 baseline, n = 59 end. Intervention group (oatmeal) n = 59 

baseline, n = 59 end. 

Mean age: Mean age: 42.2 years (no SD) for whole group. 

Male/female ratio: 63.5:/36.5 for whole group. 





39

Van Horn 1988 (Continued) 

Interventions Intervention: Inclusion of 56 g dry weight of oatmeal in the American Heart Association (AHA) fatmodified 

diet, isocalorically substituted for other foods. 

Control: AHA fat-modified diet with no oat products. 

Assessment of dietary compliance: 3-day food records every 4 weeks. 


Outcomes Main outcomes: Total cholesterol, LDL cholesterol. 

Other outcomes: None. 

Notes Dietary fibre intake - not specifically reported for subgroup with baseline total cholesterol > 198mg/dL . 

For whole group the increase in soluble fibre intake was statistically significantly greater at weeks 4 and 8 

for the oatmeal group (P < 0.005). There was no significant difference in insoluble fibre intake. 

Risk of bias 



Van Horn 1991 










Participants Diagnosis of CHD or risk factors: Hypercholesterolemic individuals previously found to have serum total 

cholesterol levels above 5.20 mmol/L. 

Exclusion criteria: Those on lipid-lowering drugs or anti-hypertensive medication; diabetic, pregnant or 

lactating; body weight > 1.5 times desirable weight; on a weight loss diet. 

Medications used: No lipid-lowering medication used for 6 weeks prior to trial. 


n = 156 randomised to 7 groups, 148 completed. For this review only those in the OM-28 oatmeal group 

have been included: OM-28 n = 20 (baseline and follow-up); control: n = 15 (baseline and follow-up). 

Mean age: 51.1 years (no SD) 




Interventions Intervention: Two packets (56.7 g dry weight) of instant oats per day, substituting oats for other carbohydrate 

foods in the usual diet. 

Control: The control group was aked to maintain usual intake throughout the study. 

Assessment of dietary compliance: 3-day food records at baseline, 4 and 8 weeks. 



40

Van Horn 1991 (Continued) 


Outcomes Main outcomes: Total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, blood pressure, bodyweight, 

body mass index. 

Other outcomes: VLDL cholesterol. 

Notes Dietary fibre intake - the study reports statistically significant differences between the oatmeal (Group 

1) and control groups (Group 2) for intake of total fibre (difference = 4.2 g P < 0.001); soluble fibre ( 

difference = 1.8 g P < 0.001) and insoluble fibre (difference = 2.3 g P < 0.01) 

Risk of bias 



Karmally 2005 - the authors (W. Karmally) have confirmed to us that the wholegrain oat cereal was a wholegrain cereal even though it 

is described as an oat bran cereal in the text of the review. 



41

Characteristics of excluded studies [ordered by study ID] 

Anderson 1978 Not specifically wholegrain 

Not RCT or CCT 

Anderson 1979 Not specifically wholegrain 

Participants not free-living 


Intervention < 4 weeks 

Asp 1981 Not specifically wholegrain 

Cannot isolate the effect of wholegrain 


Behall 2004a Cannot isolate the effect of wholegrain. (Intervention groups are barley, barley and wholegrain or wholegrain. 

Not clear if all the barley based foods are wholegrain but any comparison would be wholegrain versus wholegrain). 

Behall 2004b Cannot isolate the effect of wholegrain. (Intervention groups are barley, barley and wholegrain or wholegrain. 

Not clear if all the barley based foods are wholegrain but any comparison would be wholegrain versus wholegrain). 

Birkeland 1991 From translation of paper, both the intervention and control groups were given products containing oat bran 

which does not meet the definition of wholegrain for this review. 

Birketvedt 2000 Not wholegrain 

Booyens 1966 Participants not diagnosed with CHD or risk factors 

Bourdon 1999 Not wholegrain 


Participants not diagnosed with CHD or risk factors 

Bruttomesso 1989 Not specifically wholegrain 

Burr 1989 Not specifically wholegrain 

Cairella 1995 Not specifically wholegrain 

Chandalia 2000 Not specifically wholegrain 

Collier 1982 Intervention < 4 weeks 

Comi 1995 Not specifically wholegrain 

Crapo 1981 Not wholegrain 




42

(Continued) 

Data 1980 Intervention < 4 weeks 

Davy 2002a Comparison is wholegrain versus wholegrain 

Cannot isolate effect of wholegrain 

Davy 2002b Cannot isolate the effect of wholegrain 

Eliasson 1992 Not wholegrain 

Fehily 1986 Participants not diagnosed with CHD or risk factors 

Fischer 2000 Not specifically wholegrain 

Fordyce-Baum 1989 Product is described as a whole wheat protein isolate. We contacted the authors but were unable to obtain 

any further information on the nature of the product. 

Fraser 1981 Participants not diagnosed with CHD or risk factors 


Fung 2002 Not RCT or CCT 

Golay 1992 Not specifically wholegrain 


Guzic 1994 Not wholegrain 

Hagander 1985 Intervention < 4 weeks 

Hagander 1988 Not specifically wholegrain 

He 1995 Not RCT or CCT 

Heaton 1976 Participants not diagnosed with CHD or risk factors 

Not concurrent control? 

Hoffman 1982 Not specifically wholegrain 




Hollenbeck 1986 Not specifically wholegrain 

Cannot isolate effect of wholegrain 

Hunninghake 1994 Not wholegrain 

Jacobs 2002 Outcome is serum enterolactone which was not a specified outcome for this review 



43

(Continued) 

Jang 2001 Not specifically wholegrain 


Jenkins 1985 Not specifically wholegrain 


Jenkins 1993 Not specifically wholegrain 

Judd 1981 Participants not diagnosed with CHD or risk factors 

Cannot isolate effect of wholegrains 



Juntunen 2002 Participants not diagnosed with CHD or risk factors 


Juntunen 2003 Intervention group consumed wholemeal rye bread enriched with rye bran - cannot isolate the effect of 

wholegrain. 

Confirmation of composition of bread received from authors (K. Juntunen). 

Kabir 2002 Cannot isolate the effect of wholegrain 

Karlstrom 1984 Not specifically wholegrain 



Katz 2001a Cannot isolate the effect of wholegrain 


Katz 2001b Participants not diagnosed with CHD or risk factors 


Kay 1977 Not wholegrain 




Kay 1981 Not specifically wholegrain 



Kesaniemi 1990 Not specifically wholegrain 


Kleemola 1999 Not wholegrain 

Kris-Etherton 2002 Not specifically wholegrain 

Lakshmi 1996 Intervention < 4 weeks 



44

(Continued) 

Leinonen 1999 Participants not diagnosed with CHD or risk factors 


Liese 2003 Not RCT or CCT 

Lousley 1984 Not specifically wholegrain 

Different macronutrient (carbohydrate)compositions 

MacMahon 1998 Not wholegrain 

Manhire 1981 Intervention is the effect of wholegrain plus the withdrawal of refined sugars - cannot isolate the effect of 

wholegrain. 

Mathur 1968 Not specifically wholegrain 



McIntosh 1991 Cannot specifically isolate the effect of wholegrain 

Montonen 2003 Not RCT or CCT 

Nielsen 1988 Not wholegrain 


O’Kell 1988 Participants not diagnosed with CHD or risk factors 

Odes 1993 Not wholegrain cereal 

Pacy 1986 Not RCT or CCT 

Poulter 1993 Not all participants diagnosed with CHD or risk factors 


Reynolds 1989 Abstract only - no full paper found 

Attempted to contact authors but no further information could be obtained. 

Results quoted appear to be average of 2 and 4 week results not end results after 4 weeks. 

Rigaud 1990 Not wholegrain 

Roth 1985 Participants not diagnosed with CHD or at risk of CHD 

Russ 1985 High fibre versus low fibre - not specifically wholegrain 

Rytter 1996 Not specifically wholegrain 


Saltzman 2001a Participants not diagnosed with CHD or risk factors 

Not all participants free-living 



45

(Continued) 

Saltzman 2001b Participants not diagnosed with CHD or risk factors 

Schlamowitz 1987 Not wholegrain 

Turnbull 1987 Comparison is rolled oats versus wheat but it is not clear from the paper whether the wheat products used 

in the comparison were wholegrain or refined grain. The authors were contacted but no further details were 

obtained. 

Turnbull 1989 Comparison is rolled oats versus wheat but it is not clear from the paper whether the wheat products used 

in the comparison were wholegrain or refined grain. The authors were contacted but no further details were 

obtained. 

Turpeinen 2000 Participants not diagnosed with CHD or risk factors 

Van Horn 1986 Participants not dignosed with CHD or risk factors 

Van Horn 2001 Cannot isolate the effects of wholegrain (intervention is oats and oat bran) 

Willms 1987 Participants not free-living 


Wolever 2003 Not specifically wholegrain 

Wolffenbuttel 1992 Intervention is not specifically wholegrain 

Wursch 1991 Not specifically wholegrain 


Characteristics of ongoing studies [ordered by study ID] 

FSA 2005a 

Trial name or title Randomised controlled trial to test the impact of increased consumption of wholegrain foods on cardiovascular 

disease risk (the WHOLEheart study). University of Newcastle and MRC Cambridge Human Nutrition 

Research Centre). Funded by the UK Food Standards Agency (project no. N02036). Parallel RCT study in 

free-living subjects with three treatment arms recruited in 2 cohorts in two different centres. 

Methods 

Participants 300 men and women, 150 at each of the participating centre, aged 30-65 years with a BMI>25 kg/m3. 

Interventions Treatment A - control, no intervention. 

Treatment B - Consuming 3 portions of wholegrain food per day for 3 months. 

Treatment C - Consuming 3 portions of wholegrain food per day for 2 months increasing to 6 portions per 

day for a further 2 months. 



46

FSA 2005a (Continued) 

Outcomes The primary outcome measure will be LDL cholesterol. Other outcome measures to be assessed are: 

Body composition, fasting lipid profile, insulin sensitivity, inflammatory status and markers of endothelial 

function, blood pressure, dietary change. 

Starting date Start date 01/01/2005. End date 31/12/2007 

Contact information Dr. Chris Seal, University of Newcastle, School of Agriculture, Food and Rural Development. 

(chris.seal@ncl.ac.uk) 

Notes http://www.food.gov.uk/multimedia/pdfs/reslistnov05.pdf. Also details from personal communication from 

Chris Seal and from website. 

FSA 2005b 

Trial name or title Comparison of effects of increased wholegrain foods on markers of cardiovascular disease risk. Funded by 

Food Standards Agency, UK (Project no. N02035). Collaboration between the University of Aberdeen, the 

Rowett Research Institute and The Robert Gordon University. 

Methods 

Participants Volunteers aged between 40-65 

Interventions Comparison of wheat-based wholegrain diet with an oat and wheat-based diet and a control diet. 

Outcomes Weight, blood pressure, cholesterol and other outcomes. 

Starting date Start date 01/01/2005. End date 30/06/2009. 

Contact information Dr. Frank Thies, Dept. of Medicine and Therapeutics, Polwarth Building, Foresterhill, University of Aberdeen 

AB25 2ZD. 

(f.thies@abdn.ac.uk) 

Notes http://www.food.gov.uk/multimedia/pdfs/reslistnov05.pdf. Details also from http://www.abdn.ac.uk/mediareleases/release.php?id=289 



47

D A T A A N D A N A L Y S E S 

Comparison 1. Total cholesterol 

Outcome or subgroup title 

No. of 

studies 

No. of 

participants Statistical method Effect size 

1 4 week outcomes 4 321 Mean Difference (IV, Fixed, 95% CI) -0.16 [-0.34, 0.01] 

1.1 Parallel studies (all oats) 3 241 Mean Difference (IV, Fixed, 95% CI) -0.12 [-0.32, 0.09] 

1.2 Crossover studies (rye) 1 80 Mean Difference (IV, Fixed, 95% CI) -0.30 [-0.65, 0.05] 

2 All endpoint outcomes 9 738 Mean Difference (IV, Fixed, 95% CI) -0.20 [-0.31, -0.10] 

2.1 Parallel studies (all oats) 8 658 Mean Difference (IV, Fixed, 95% CI) -0.19 [-0.30, -0.08] 


Comparison 2. LDL cholesterol 


No. of 

studies 

No. of 


1 4 week outcomes 4 321 Mean Difference (IV, Fixed, 95% CI) -0.19 [-0.37, -0.01] 



2 All endpoint outcomes 9 738 Mean Difference (IV, Fixed, 95% CI) -0.18 [-0.28, -0.09] 

2.1 Parallel studies (all oats) 8 658 Mean Difference (IV, Fixed, 95% CI) -0.18 [-0.28, -0.09] 


Comparison 3. HDL cholesterol 


No. of 

studies 

No. of 


1 4 week outcomes 3 203 Mean Difference (IV, Fixed, 95% CI) 0.03 [-0.06, 0.11] 

1.1 Parallel studies (all oats) 2 123 Mean Difference (IV, Fixed, 95% CI) 0.04 [-0.06, 0.14] 

1.2 Crossover studies (rye) 1 80 Mean Difference (IV, Fixed, 95% CI) Not estimable 

2 All endpoint outcomes 7 532 Mean Difference (IV, Fixed, 95% CI) 0.00 [-0.05, 0.05] 





48

Comparison 4. Triglycerides 


No. of 

studies 

No. of 


1 4 week outcomes 3 203 Mean Difference (IV, Fixed, 95% CI) 0.01 [-0.13, 0.16] 



2 All endpoint outcomes (Keenan 

data as SD) 

7 496 Mean Difference (IV, Fixed, 95% CI) 0.01 [-0.09, 0.11] 



3 All endpoint outcomes (Keenan 

data as SEM) 

7 496 Mean Difference (IV, Fixed, 95% CI) -0.01 [-0.11, 0.09] 



Comparison 5. Body weight (kg) 


No. of 

studies 

No. of 


1 All endpoint outcomes 7 Mean Difference (IV, Fixed, 95% CI) Subtotals only 





49

Analysis 1.1. Comparison 1 Total cholesterol, Outcome 1 4 week outcomes. 

Review: Wholegrain cereals for coronary heart disease 

Comparison: 1 Total cholesterol 

Outcome: 1 4 week outcomes 

Study or subgroup Wholegrain Control Mean Difference Weight Mean Difference 

1 Parallel studies (all oats) 

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI 

Reynolds 2000 22 5.87 (0.56) 21 5.83 (0.6) 26.5 % 0.04 [ -0.31, 0.39 ] 

Van Horn 1988 59 5.45 (0.88) 59 5.79 (1.06) 25.9 % -0.34 [ -0.69, 0.01 ] 

Van Horn 1991 42 6.28 (0.92) 38 6.32 (0.84) 21.5 % -0.04 [ -0.43, 0.35 ] 

Subtotal (95% CI) 123 118 74.0 % -0.12 [ -0.32, 0.09 ] 

Heterogeneity: Chi 2 = 2.48, df = 2 (P = 0.29); I 2 =19% 

Test for overall effect: Z = 1.10 (P = 0.27) 

2 Crossover studies (rye) 

Leinonen 2000 40 6.2 (0.8) 40 6.5 (0.8) 26.0 % -0.30 [ -0.65, 0.05 ] 

Subtotal (95% CI) 40 40 26.0 % -0.30 [ -0.65, 0.05 ] 

Heterogeneity: not applicable 


Total (95% CI) 163 158 100.0 % -0.16 [ -0.34, 0.01 ] 



Test for subgroup differences: Chi 2 = 0.78, df = 1 (P = 0.38), I 2 =0.0% 



-1 -0.5 0 0.5 1 

Favours treatment Favours control 

50

Analysis 1.2. Comparison 1 Total cholesterol, Outcome 2 All endpoint outcomes. 


Comparison: 1 Total cholesterol 

Outcome: 2 All endpoint outcomes 




Davidson 1991 20 6.54 (0.68) 15 6.79 (0.85) 3.9 % -0.25 [ -0.77, 0.27 ] 

Johnston 1998 62 6.04 (0.61) 62 6.23 (0.54) 26.1 % -0.19 [ -0.39, 0.01 ] 

Karmally 2005 73 5.14 (0.65) 79 5.21 (0.7) 23.3 % -0.07 [ -0.28, 0.14 ] 

Keenan 2002 10 4.73 (0.47) 8 5.11 (0.48) 5.5 % -0.38 [ -0.82, 0.06 ] 

Pins 2002 45 4.66 (0.87) 43 5.34 (1.11) 6.2 % -0.68 [ -1.10, -0.26 ] 

Reynolds 2000 22 5.87 (0.56) 21 5.83 (0.6) 8.9 % 0.04 [ -0.31, 0.39 ] 

Van Horn 1988 59 5.47 (0.84) 59 5.78 (1.03) 9.3 % -0.31 [ -0.65, 0.03 ] 

Van Horn 1991 42 6.15 (0.86) 38 6.3 (0.82) 7.9 % -0.15 [ -0.52, 0.22 ] 

Subtotal (95% CI) 333 325 91.3 % -0.19 [ -0.30, -0.08 ] 




Leinonen 2000 40 6.2 (0.8) 40 6.5 (0.8) 8.7 % -0.30 [ -0.65, 0.05 ] 

Subtotal (95% CI) 40 40 8.7 % -0.30 [ -0.65, 0.05 ] 



Total (95% CI) 373 365 100.0 % -0.20 [ -0.31, -0.10 ] 






-1 -0.5 0 0.5 1 


51

Analysis 2.1. Comparison 2 LDL cholesterol, Outcome 1 4 week outcomes. 


Comparison: 2 LDL cholesterol 





Reynolds 2000 22 3.99 (0.52) 21 3.96 (0.6) 28.4 % 0.03 [ -0.31, 0.37 ] 

Van Horn 1988 59 3.18 (0.79) 59 3.64 (1.14) 25.6 % -0.46 [ -0.81, -0.11 ] 

Van Horn 1991 42 4.24 (0.87) 38 4.39 (0.75) 25.4 % -0.15 [ -0.51, 0.21 ] 

Subtotal (95% CI) 123 118 79.4 % -0.19 [ -0.39, 0.02 ] 




Leinonen 2000 40 4.3 (0.9) 40 4.5 (0.9) 20.6 % -0.20 [ -0.59, 0.19 ] 

Subtotal (95% CI) 40 40 20.6 % -0.20 [ -0.59, 0.19 ] 



Total (95% CI) 163 158 100.0 % -0.19 [ -0.37, -0.01 ] 






-1 -0.5 0 0.5 1 


52

Analysis 2.2. Comparison 2 LDL cholesterol, Outcome 2 All endpoint outcomes. 


Comparison: 2 LDL cholesterol 


Study or subgroup Wholegrain Control diet Mean Difference Weight Mean Difference 



Davidson 1991 20 4.47 (0.61) 15 4.79 (0.73) 4.0 % -0.32 [ -0.78, 0.14 ] 

Johnston 1998 62 3.93 (0.49) 62 4.15 (0.42) 32.5 % -0.22 [ -0.38, -0.06 ] 

Karmally 2005 73 3.43 (0.56) 79 3.49 (0.58) 25.5 % -0.06 [ -0.24, 0.12 ] 

Keenan 2002 10 2.94 (0.63) 8 3.37 (0.45) 3.4 % -0.43 [ -0.93, 0.07 ] 

Pins 2002 45 3.03 (0.74) 43 3.41 (0.79) 8.2 % -0.38 [ -0.70, -0.06 ] 

Reynolds 2000 22 3.99 (0.52) 21 3.96 (0.6) 7.4 % 0.03 [ -0.31, 0.37 ] 

Van Horn 1988 59 3.25 (0.76) 59 3.42 (1.16) 6.7 % -0.17 [ -0.52, 0.18 ] 

Van Horn 1991 42 4.16 (0.83) 38 4.44 (0.77) 6.8 % -0.28 [ -0.63, 0.07 ] 

Subtotal (95% CI) 333 325 94.6 % -0.18 [ -0.28, -0.09 ] 

Heterogeneity: Chi 2 = 6.55, df = 7 (P = 0.48); I 2 =0.0% 



Leinonen 2000 40 4.3 (0.9) 40 4.5 (0.9) 5.4 % -0.20 [ -0.59, 0.19 ] 

Subtotal (95% CI) 40 40 5.4 % -0.20 [ -0.59, 0.19 ] 



Total (95% CI) 373 365 100.0 % -0.18 [ -0.28, -0.09 ] 






-1 -0.5 0 0.5 1 


53

Analysis 3.1. Comparison 3 HDL cholesterol, Outcome 1 4 week outcomes. 


Comparison: 3 HDL cholesterol 


Study or subgroup Wholegrain Control diet Mean Difference Weight Mean Difference 



Reynolds 2000 22 1.29 (0.33) 21 1.19 (0.27) 22.9 % 0.10 [ -0.08, 0.28 ] 

Van Horn 1991 42 1.36 (0.28) 38 1.35 (0.26) 52.9 % 0.01 [ -0.11, 0.13 ] 

Subtotal (95% CI) 64 59 75.9 % 0.04 [ -0.06, 0.14 ] 




Leinonen 2000 40 1.4 (0.4) 40 1.4 (0.4) 24.1 % 0.0 [ -0.18, 0.18 ] 

Subtotal (95% CI) 40 40 24.1 % 0.0 [ -0.18, 0.18 ] 



Total (95% CI) 104 99 100.0 % 0.03 [ -0.06, 0.11 ] 






-1 -0.5 0 0.5 1 


54

Analysis 3.2. Comparison 3 HDL cholesterol, Outcome 2 All endpoint outcomes. 


Comparison: 3 HDL cholesterol 





Davidson 1991 20 1.48 (0.33) 15 1.34 (0.45) 3.3 % 0.14 [ -0.13, 0.41 ] 

Johnston 1998 62 1.29 (0.33) 62 1.25 (0.28) 20.8 % 0.04 [ -0.07, 0.15 ] 

Karmally 2005 73 0.93 (0.26) 79 0.97 (0.23) 39.5 % -0.04 [ -0.12, 0.04 ] 

Keenan 2002 10 1.07 (0.32) 8 1.06 (0.23) 3.7 % 0.01 [ -0.24, 0.26 ] 

Reynolds 2000 22 1.29 (0.33) 21 1.19 (0.27) 7.5 % 0.10 [ -0.08, 0.28 ] 

Van Horn 1991 42 1.28 (0.29) 38 1.3 (0.25) 17.3 % -0.02 [ -0.14, 0.10 ] 

Subtotal (95% CI) 229 223 92.1 % 0.00 [ -0.05, 0.05 ] 




Leinonen 2000 40 1.4 (0.4) 40 1.4 (0.4) 7.9 % 0.0 [ -0.18, 0.18 ] 

Subtotal (95% CI) 40 40 7.9 % 0.0 [ -0.18, 0.18 ] 



Total (95% CI) 269 263 100.0 % 0.00 [ -0.05, 0.05 ] 






-1 -0.5 0 0.5 1 


55

Analysis 4.1. Comparison 4 Triglycerides, Outcome 1 4 week outcomes. 


Comparison: 4 Triglycerides 





Reynolds 2000 22 1.3 (0.47) 21 1.48 (0.78) 13.9 % -0.18 [ -0.57, 0.21 ] 

Van Horn 1991 42 1.48 (0.92) 38 1.26 (0.61) 18.1 % 0.22 [ -0.12, 0.56 ] 

Subtotal (95% CI) 64 59 32.1 % 0.05 [ -0.21, 0.30 ] 




Leinonen 2000 40 1.1 (0.4) 40 1.1 (0.4) 67.9 % 0.0 [ -0.18, 0.18 ] 

Subtotal (95% CI) 40 40 67.9 % 0.0 [ -0.18, 0.18 ] 



Total (95% CI) 104 99 100.0 % 0.01 [ -0.13, 0.16 ] 






-1 -0.5 0 0.5 1 


56

Analysis 4.2. Comparison 4 Triglycerides, Outcome 2 All endpoint outcomes (Keenan data as SD). 



Outcome: 2 All endpoint outcomes (Keenan data as SD) 




Davidson 1991 20 1.28 (0.61) 15 1.42 (0.54) 6.8 % -0.14 [ -0.52, 0.24 ] 

Karmally 2005 73 1.71 (0.71) 79 1.63 (0.75) 18.4 % 0.08 [ -0.15, 0.31 ] 

Keenan 2002 10 2.11 (0.66) 8 1.7 (0.24) 5.1 % 0.41 [ -0.03, 0.85 ] 

Pins 2002 45 1.95 (0.47) 43 2.08 (0.52) 23.1 % -0.13 [ -0.34, 0.08 ] 

Reynolds 2000 22 1.3 (0.47) 21 1.48 (0.78) 6.6 % -0.18 [ -0.57, 0.21 ] 

Van Horn 1991 42 1.54 (1.04) 38 1.22 (0.53) 7.8 % 0.32 [ -0.04, 0.68 ] 

Subtotal (95% CI) 212 204 67.7 % 0.01 [ -0.11, 0.13 ] 




Leinonen 2000 40 1.1 (0.4) 40 1.1 (0.4) 32.3 % 0.0 [ -0.18, 0.18 ] 

Subtotal (95% CI) 40 40 32.3 % 0.0 [ -0.18, 0.18 ] 



Total (95% CI) 252 244 100.0 % 0.01 [ -0.09, 0.11 ] 






-1 -0.5 0 0.5 1 


57

Analysis 4.3. Comparison 4 Triglycerides, Outcome 3 All endpoint outcomes (Keenan data as SEM). 



Outcome: 3 All endpoint outcomes (Keenan data as SEM) 




Davidson 1991 20 1.28 (0.61) 15 1.42 (0.54) 7.1 % -0.14 [ -0.52, 0.24 ] 

Karmally 2005 73 1.71 (0.71) 79 1.63 (0.75) 19.3 % 0.08 [ -0.15, 0.31 ] 

Keenan 2002 10 2.11 (2.09) 8 1.7 (0.68) 0.5 % 0.41 [ -0.97, 1.79 ] 

Pins 2002 45 1.95 (0.47) 43 2.08 (0.52) 24.2 % -0.13 [ -0.34, 0.08 ] 

Reynolds 2000 22 1.3 (0.47) 21 1.48 (0.78) 6.9 % -0.18 [ -0.57, 0.21 ] 

Van Horn 1991 42 1.54 (1.04) 38 1.22 (0.53) 8.2 % 0.32 [ -0.04, 0.68 ] 

Subtotal (95% CI) 212 204 66.2 % -0.02 [ -0.14, 0.11 ] 




Leinonen 2000 40 1.1 (0.4) 40 1.1 (0.4) 33.8 % 0.0 [ -0.18, 0.18 ] 

Subtotal (95% CI) 40 40 33.8 % 0.0 [ -0.18, 0.18 ] 



Total (95% CI) 252 244 100.0 % -0.01 [ -0.11, 0.09 ] 






-1 -0.5 0 0.5 1 


58

Analysis 5.1. Comparison 5 Body weight (kg), Outcome 1 All endpoint outcomes. 


Comparison: 5 Body weight (kg) 





Johnston 1998 62 83.4 (13.8) 62 79.2 (12) 16.2 % 4.20 [ -0.35, 8.75 ] 

Karmally 2005 73 77.58 (12.74) 79 72.72 (11.97) 21.6 % 4.86 [ 0.92, 8.80 ] 

Keenan 2002 10 84.6 (18) 8 94.9 (17.2) 1.3 % -10.30 [ -26.63, 6.03 ] 

Pins 2002 45 83 (5.9) 43 83.4 (5.8) 56.1 % -0.40 [ -2.84, 2.04 ] 

Reynolds 2000 22 69.8 (13.1) 21 75.5 (14.7) 4.8 % -5.70 [ -14.04, 2.64 ] 

Subtotal (95% CI) 212 213 100.0 % 1.10 [ -0.73, 2.93 ] 




Leinonen 2000 40 72.6 (8.1) 40 72.9 (8.4) 4.7 % -0.30 [ -3.92, 3.32 ] 

Pereira 2002 12 84.8 (1) 12 85.1 (1) 95.3 % -0.30 [ -1.10, 0.50 ] 

Subtotal (95% CI) 52 52 100.0 % -0.30 [ -1.08, 0.48 ] 



Test for subgroup differences: Chi 2 = 1.90, df = 1 (P = 0.17), I 2 =47% 

W H A T ’ S N E W 

Last assessed as up-to-date: 14 January 2007. 

9 September 2008 Amended Converted to new review format. 



-10 -5 0 5 10 


59

H I S T O R Y 

Protocol first published: Issue 4, 2004 

Review first published: Issue 2, 2007 

15 January 2007 New citation required and conclusions have changed Substantive amendment 

C O N T R I B U T I O N S O F A U T H O R S 

Dr S Kelly 

Prepared and designed the protocol for the review. Developed and ran the search strategy. Organised the retrieval of papers and screened 

papers for inclusion and exclusion. Extracted data from included papers and took the primary role in writing the review. 

Dr G Frost 

Conceived the review and provided a methodological, policy and clinical perspective on the data. 

Dr C Summerbell 

Provided a methodological, policy and clinical perspective on the data. 

Dr A Brynes 

For purposes of dual data extraction extracted data from papers and contributed to quality assessment of studies. 

Mrs V Whittaker 

Advised on statistics, meta-analysis and quality assessment of studies. 

D E C L A R A T I O N S O F I N T E R E S T 

Gary Frost is a qualified dietitian. 

Carolyn Summerbell is a qualified dietitian. 

Audrey Brynes is a qualified dietitian 

S O U R C E S O F S U P P O R T 

Internal sources 

• University of Teesside, Middlesbrough, UK. 

• Hammersmith Hospital, UK. 



60

External sources 

• No sources of support supplied 

I N D E X T E R M S 

Medical Subject Headings (MeSH) 

∗ Cereals; Cholesterol [blood]; Cholesterol, LDL [blood]; Coronary Disease [blood; ∗ diet therapy]; Randomized Controlled Trials as 

Topic; Risk Factors 

MeSH check words 

Humans 



61

Wholegrain cereals for coronary heart disease (Review) - Teesside's ...

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