Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies
BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i2716 (Published 14 June 2016) Cite this as: BMJ 2016;353:i2716All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
It is good to read a research article on "Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies". [1]
For whole grains to be effective, they must contain all components of the entire grain kernel, including the bran, the germ and the endosperm. Because when whole grains are ground into flours, most grains act like sugar in the body and thus reduce the beneficial effects.[2]
It is a well known fact that long use of whole grains reduces lipid levels, reduces blood pressure, redistributes fat and maintains weight, regulates blood sugar, provides essential minerals, vitamin B & C, may reduce asthma and reduces cancer risk. [3]
In a meta-analysis of prospective cohort studies, the inverse association is seen with whole grain consumption and is linked with longevity.[4]
There are reports from the studies that a healthy diet with whole grains, fruits, vegitables (Prudent diet) protects against cognitive decline and diminishes the adverse effects of high adherence to Western diet on cognitive decline.[5]
Studies revealed that whole grains, fruit & milk dietary pattern is associated with improved bone mineral density (BMD) in Korean healthy adults [6] and that whole grains consumption in breakfast is linked with higher test scores in elementary school students. [7]
There are different types and nomenclatures of diets (with pro and cons) that depend on prevalent regions, and composition of proteins, fats, carbohydrates, minerals, vitamins and fibre.
Regards,
Dr Rajiv Kumar, Dr Jagjit Singh.
Faculty,
Deptt. of Pharmacology.
Government Medical College & Hospital Chandigarh, 160030, India.
DRrajiv.08@gmail.com
References:
1. BMJ 2016;353:i2716
2. https://experiencelife.com/article/the-truth-about-refined-grains/
3. http://www.huffingtonpost.com/entry/whole-grains-health-benefits_n_56550...
4. Circulation. 2016 Jun 14;133(24):2370-80.
5. Alzheimers Dement. 2016 Feb;12(2):100-9.
6. European Journal of Clinical Nutrition (2015) 69, 442–448.
7. J Am Coll Nutr. 2016 May-Jun;35(4):326-33.
Competing interests: No competing interests
I completely agree with Professor Colquhoun who can’t see the point of publishing this questionable study.1 It makes no sense to claim that eating seven servings of whole grains each day is healthy. The very basis of a health giving Stone Age Diet is a varied consumption of meat, fish, vegetables and fruit. Wheat, corn, rye and cow’s milk are common food allergens increasing the risk of headache, migraine and hypertension and arthritis.2,3
It is not enough to recognize that whole grains have more nutrients than processed grains because eating excess grains of any type can interfere with the gut absorption of nutrients.4 For example, I remember a lecture from Professor Nick Solomons. His team had found that a meal of oysters quickly raised serum zinc levels but adding beans halved the increase. When beans plus corn were added to the oysters there was no increase at all in serum zinc.
Much of the inadequacies of modern diets has been blamed on excessive consumption of refined carbohydrates. However, Solomons and colleagues found no significant differences in absorption of zinc absorption in Guatemalan schoolchildren children fed low-phytate maize, either the isohybrid wild-type maize or a local maize.5
Damien Downing reviewed the history of Man’s diets.6 The apes from which we evolved had predominantly fruit-based diets 8 to 10 million years ago. The hominids then introduced starchy root vegetables. Two million years ago we started to eat more meat but it was not until 5000 years ago that dairy products and cereal became an important part of human diets. Advising patients to use a varied high protein stone age diet is the basis of drug-free management in my experience.
1 Aune D, Keum N, Giovannucci E, et al. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. BMJ 2016;353:i2716.
2 Grant ECG. Food allergies and migraine. Lancet 1979;1:966-69.
3 Darlington LG, Ramsay NW. Review of dietary changes for rheumatoid arthritis. Brit J Rheumatology 1993; 32:507-14.
4 Burk RF, Solomons NW. Trace elements and vitamins and bioavailability as related to wheat and wheat foods. Am J Clin Nutr. 1985 May;41(5 Suppl):1091-10
5 Mazariegos M1, Hambidge KM, Krebs NF, Westcott JE, Lei S, Grunwald GK, Campos R, Barahona B, Raboy V, Solomons NW. Zinc absorption in Guatemalan schoolchildren fed normal or low-phytate maize. Am J Clin Nutr 2006 Jan;83(1):59-64.
6 Downing D. The history of man in four diets. J Nutr Environ Med 2003:13:139-41.
Competing interests: No competing interests
Aune and others show an inverse, dose-dependent relationship between whole grain consumption and all-cause mortality.[1]
They assert that this provides strong evidence to increase whole grain food intake in the general population to reduce risk of chronic diseases and premature mortality.The problem drawing causation from observational studies is well described. Egger and others provide two useful examples in their text book Systematic reviews in healthcare- meta-analysis in context.[2]
Firstly, cohort studies have shown a dose-dependent response for cigarette-smoking and suicide. However, this effect is likely due to associated psycho-social factors rather than a cause of cigarette smoking. Eating whole grain, which is recommended as a healthy life-style choice, may be associated with any number of confounders such as education, exercise, and the consumption (or lack of) of other foods.
This potential problem, one of selection bias and confounding, is illustrated in a second example described by Egger and others. In a meta-analysis of observational studies beta-carotene has been shown to be associated with beneficial cardiovascular outcome, though a meta-analysis of randomised controlled trial showed a worse cardiovascular mortality.
The authors recommend a high intake of wholegrain food. In an obese patient with type two diabetes and low activity levels this advice may not be beneficial. A distinction needs to be made between the absolute and proportional intake of carbohydrate. For some, a high calorie intake of wholegrain food may be unhelpful, whilst calorie restriction, through very low calorie diets or diets low in carbohydrate and high in fat, may have health benefits.[3 4]
[1] Aune D, Keum N, Giovannucci E, et al. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. BMJ. 2016;353:i2716. PubMed PMID: 27301975.
[2] Egger M, Smith GD, Altman DG. Systematic reviews in health care, meta-analysis in context: BMJ Publishing Group; 2001.
[3] Taylor R. Type 2 diabetes: etiology and reversibility. Diabetes care. 2013 Apr;36(4):1047-55. PubMed PMID: 23520370. Pubmed Central PMCID: PMC3609491.
[4] Elhayany A, Lustman A, Abel R, et al. A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study. Diabetes, obesity & metabolism. 2010 Mar;12(3):204-9. PubMed PMID: 20151996.
Competing interests: No competing interests
The meta-analysis of Aune et al attempts to put a value on old-fashioned common sense, but risks exaggerating its value by its narrow focus on a single class of unrefined food.[1]
As David Colquhoun has noted in these responses, confounding in regard to this question is a complex problem.[2]
People who pay the extra money for whole grains and go out of their way to prepare them are, overall, a breed apart. (Indeed, one of the benefits of refined grains in the past was a shorter cooking time, and thus a lower expenditure on fuel, perhaps a critical advantage in highly populated, deforested nations). People who chose whole grains may thus have more money and leisure time, or be better educated or more interested in health, or, in some cultures, be more connected to family and cultural traditions.
Perhaps more significantly, people who use whole grains are likely to be opposed to the consumption of highly refined grains and other processed foods. Thus, they are not exposed to high-GI carbohydrates, the supplementary vitamins and minerals added to refined flour (including iron), and bleaching agents, and are perhaps less exposed to the baffling array of food additives that seem to be necessary for the modern production of bread. They are also unlikely to be people who consume deep-fried foods often.
All these factors predict good health in people who eat whole grains, without requiring that specific nutritional and non-nutritive factors in whole grains provide the benefit. In fact it may be that people who ate most whole grains when questioned at the beginning of the more recent long term diet studies were the most likely to have given up grains altogether, or to have eliminated gluten grains from their diets, by the end of the study, as these practices have partly replaced wholegrain eating as health fads.
We can reduce such confounding by looking at an RCT where whole grains (by one possible definition among many) were part of an intervention where mortality was an endpoint. The Diet and Reinfarction Trial (DART), 1989, took 2,033 British men who had already suffered from an acute MI and divided them into six groups to test dietary advice to a) decrease saturated fat and replace it with polyunsaturated fat, b) increase fish intake, c) increase cereal fibre intake by the use of wholegrain bread and extra bran. Only the higher fish group saw a significant reduction in MI and all-cause mortality; the other interventions saw large (but non-significant, given the small n= and moderate duration of 2 years) increases in MI and all-cause mortality.[3]
"Those randomized to the cereal fibre group were advised to have at least six slices of wholemeal bread per day, or the equivalent amount of cereal fibre from a mixture of wholemeal bread, high fibre breakfast cereals and wheat bran. An exchange list was provided for these items. Bran tablets (Fybranta, Norgine Ltd, UK) were offered as a supplement where necessary." These tablets were only used by two subjects, while 71 of the subjects in this intervention "added wheat bran to cereals, soups or stews.". This resulted in a doubling of cereal fibre intake, and would also have increased intake of lignans and betaine.[4]
The long term effect of the various advice, reported in 2002, is also of interest.
"By February 2000, after 21147 person years of follow-up, 1083 (53%) of the men had died. Completed questionnaires were obtained from 879 (85%) of the 1030 men alive at the beginning of 1999. Relative increases in fish and fibre intake were still present at 10 y but were much smaller. The early reduction in all-cause mortality observed in those given fish advice (unadjusted hazard 0.70 (95% CI 0.54, 0.92)) was followed by an increased risk over the next 3 y (unadjusted hazard 1.31 (95% CI 1.01, 1.70). Fat and fibre advice had no clear effect on coronary or all-cause mortality. The risk of stroke death was increased in the fat advice group - the overall unadjusted hazard was 2.03 (95% CI 1.14, 3.63)."[5]
The value of such RCT information is that it underscores the extreme difficulty of translating observational findings such as those of Aune et al into beneficial interventions or dietary advice.
It is wholly plausible - indeed, it is old-fashioned common sense - that eating whole grains in place of refined grains is a healthful habit. Medical men of the past such as TL Cleave and Sir Robert McCarrison were probably not deluded when they insisted on this.[6, 7] However, both men saw wholegrain consumption as beneficial in the context of a diet relatively high in fatty animal foods (including dairy, eggs, and organ meats), fruit, and vegetables, and low in sugar and highly processed foods. They did not say that cereal consumption needed to be increased at the expense of animal foods, as it was in the late 20th century.
It is notable that the association between wholegrain intake and diabetes mortality in Aune et al is a U-shaped curve with lowest mortality at an amount that would supply 35-45g carbohydrate/day, depending on the type of grain, which is not a biologically implausible association. A pre-existing diabetes diagnosis is usually an exclusion criteria in diet studies of the type analysed in Aune et al.
Populations which had zero grain consumption prior to the arrival of colonists did not suffer from high rates of diabetes, cancer, or cardiovascular disease, but do suffer from very high rates of these diseases today following the introduction of refined grains, sugars, and oils. Thus, if there are in fact essential protective nutrients and other factors in whole grains, these must have also been available from the other foods that make up natural and minimally processed diets, and are as likely to continue to be available from these foods today.
[1] Aune D, Keum M, Giovannucci E et al. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. BMJ 2016;353:i2716
[2] http://www.bmj.com/content/353/bmj.i2716/rr-0
[3} Burr ML1, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989 Sep 30;2(8666):757-61.
[4] Fehily AM, Vaughan-Williams E, Shiels K et al. The effect of dietary advice on nutrient intakes: evidence from the diet and reinfarction trial (DART). Journal of Human Nutrition and Dietetics. Volume 2, Issue 4, pages 225–235, August 1989
[5] Ness AR, J Hughes J, Elwood PC et al. The long-term effect of dietary advice in men with coronary disease: follow-up of the Diet and Reinfarction trial (DART). EJCN. June 2002, Volume 56, Number 6, Pages 512-518
[6] http://journeytoforever.org/farm_library/Cleave/cleave_toc.html
[7} http://journeytoforever.org/farm_library/McC/McCToC.html
Competing interests: No competing interests
The authors themselves say
"People with a high intake of whole grains might have different lifestyles, diets,
or socioeconomic status than those with a low intake, thus confounding by
other lifestyle factors is a potential source of bias. "
The confounding is very obvious. That being the case, I can't see the point in publishing studies like this at all. They merely add to the confusion that does so much to discredit science.
It might be better to read John Ioannidis (BMJ 2013;347:f6698 doi: 10.1136/bmj.f6698 ), on Implausible Results in Human Nutrition Research. As he says
"Almost every single nutrient imaginable has peer reviewed publications associating it with almost any outcome"
The subtitle of his paper is
"“Definitive solutions won’t come from another million observational papers or small randomized trials“.
That being the case, is it really worth publishing yet another analysis of observational data?
Competing interests: No competing interests
What about gluten-free diets in coeliac disease and Bariatric surgery and strict diets for weight loss? Do they also suffer from various diseases (like cardiovascular diseases, cancer, diabetes, etc) those get lowered by taking whole grains. The article is not complete without making a mention of these particular categories. Or else, research should be undertaken for these categories of people.
Competing interests: No competing interests
Remarks concerning the presentation of search strategy
The benefits of whole grain consumption is surely an interesting and important topic for a systematic review. However, as an information specialist I do have some remarks concerning how the search strategy is presented in Appendix 1.
In short, this search strategy is not reproducible based on your documentation. In Appendix 1, you supply a long list of the search terms used (which is, I should say, a good start). Nonetheless, without a proper presentation how field codes were used (e.g. title and abstract only), which terms are free text and which are MeSH (in PubMed) or Emtree (Embase) terms, the searches can't be repeated.
For instance in line 70 to 80, you are using a lot of phrases. However, if you search for phrases using quotations marks in PubMed, the phrase is not automatically mapped to the corresponding MeSH term, e.g. Heart Diseases[MeSH].
Several redundant phrases are also included, e.g. "grain" and "grains" (#20–21) make #22-23 unnecessary; the same with "fiber" #40 and #41–25; and "diet" #52 and #51, #57, #58, #61.
According to your flow chart (Fig 1) for study selection, the search strategy yielded a quite huge amount of references (n=48,380), which suggests that the search was highly sensitive (necessary for a systematic review). With that said, I wondering why you retrieve so many more references in PubMed (n=39,741) in comparison to Embase (n=8,639); in general, it's always the another way around. However, without a complete documentation for each database, this can't be explained.
Did you include a librarian/information specialist in the project?
Competing interests: No competing interests