Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study
BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j1892 (Published 02 May 2017) Cite this as: BMJ 2017;357:j1892
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It makes no sense to believe that long-term gluten consumption decreases the risk of coronary heart disease based on the evidence of an epidemiological study.1 In the UK wheat is the most commonly eaten overt or “masked” food allergen. 60 Charing Cross Hospital migraine patients completed elimination and reintroduction dieting after a 5-day period of withdrawal from their usual diet and medications. The commonest foods causing adverse reactions, usually an increased pulse rates, were wheat (78%), orange (65%), eggs (45%), tea and coffee (40% each), chocolate and milk (37%) each), beef (35%), and corn, cane sugar, and yeast (33% each). Of these patients, 52 (87%) had previously been using oral contraceptives, tobacco, and/or ergotamine for an average of 3 years, 22 years, and 7.4 years respectively.2 Avoiding an average of ten common foods resulted in a dramatic fall in the number of headaches per month with 85% of patients becoming headache-free and all the patients with hypertension becoming normotensive. Previously medications averaged115 tablets/month but then reduced to half a tablet. 3
I became a founder member of the British Society for Environmental Medicine (BSEM). The BSEM text book publication, Environmental Medicine in Clinical Practice, lists the results of similar dietary exclusion and reintroduction studies in a range of conditions in both adults and children and all give similar results. “Masked” allergy to wheat and corn, and also to eggs and milk, is common in both adults and children. Wheat, cow’s milk and eggs commonly cause infantile eczema in atopic families. In my experience, infantile colic can also be caused when a lactating mother eats these foods. Increased availability of gluten free food is important, especially as there may be a link with gluten intake and increased risk of dementia in older people.4
It is mysterious why the medical profession is over-dependent on prescribing drugs but is resistant to the reality that overt or masked food allergies (known to be described by Hippocrates) are important causes of numerous illnesses including vascular diseases.
1 Lebwohl, B., et al., Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ, 2017. 357: p. j1892.
2 Grant ECG. Oral contraceptives, smoking, migraine and food allergies. Lancet 1978;2:581-2.
3 Grant ECG. Food allergies and migraine. Lancet 1979;1:966-69.
4 Stetka BS, Perimutter D. Dementia: is gluten the culprit? Medscape Jan 21, 2014
Competing interests: No competing interests
There are so many studies that prove there IS a higher risk of heart disease after long term gluten exposure! I am living proof of this and yes, I'm highly disgusted by your article. Just as MANY get upset when they read an article mocking the existence of gluten. In my case, I was only 39 yrs. Old with no prior family history of heart disease and I was in excellent health. Aerobics was part of my weekly routine and I ate wheat regularly. I had no cholesterol build up of any kind, even during my hospital stay after my heart attack! Maybe some people are more at risk than others but I do believe...Scratch that, I know inflammation is a major risk to the heart and gluten causes inflammation!!!!!! I'm now gluten free for almost 5 yrs. and am a minimal risk for future heart attacks according to my doctors!! More and more young adults are having heart attacks and many have celiac disease! There is a link!!!!!
Competing interests: No competing interests
We appreciate the interest in our study and the points raised by Dr. Pijak and colleagues. We would first like to clarify that we did not find an “absence of cardiovascular benefit of strict gluten-free diet observed”. As we discussed in the manuscript, our analysis was not based on a strict gluten-free diet as 1) we excluded patients with known coeliac disease from our analysis; and 2) our food frequency questionnaire was unable to assess the extreme of an entirely gluten-free diet. To evaluate the relative extremes of dietary gluten intake, we did conduct analyses in which we classified subjects based on decile of gluten intake. We still found no difference in the incidence of coronary heart disease even comparing the lowest to highest decile of intake. However, those in the lowest decile of gluten intake consumed a median of 2.3 grams a day, the approximate equivalent of nearly one slice of bread daily. [1]
Dr. Pijak and colleagues raise questions about the protective effect of whole grains with regard to cardiovascular outcomes. Even if not every study has shown a significant cardiovascular benefit of whole grains, all studies included in the meta-analysis cited by the authors had a point estimate indicating a reduced risk of the outcome, with relative risks ranging from 0.65 to 0.90. [2] A previous analysis of the same cohorts included in our study of gluten found that whole grains were protective against cardiovascular mortality after adjusting for the Alternate Healthy Eating Index, which takes into account intake of fruits, vegetables, nuts and legumes. [3]
The adoption of a Western diet, which often results in an increase in saturated fats and refined grains, can indeed increase cardiovascular risk, but the notion that gluten is involved in the causal pathway is without foundation. The concept that wheat intake can result in leptin resistance and therefore obesity can be empirically tested, though we suspect that the form of wheat (i.e. whole versus refined) would be relevant given the effect of its composition on satiety.
While the benefits of the paleolithic diet cited in Dr. Pijak are acknowledged, it is also worth noting that the four studies in the meta-analysis used intermediate end-points (e.g. waist circumference and systolic blood pressure) and had a follow-up time of a maximum of 6 months. [4] It is premature to conclude, based on these data, that such a diet is beneficial or tenable in the long-term for the majority of individuals.
Ultimately, we agree with the authors that “a well-balanced gluten-free diet should not necessarily put people without coeliac disease at a higher risk for cardiometabolic diseases.” A gluten-free diet can be rich in whole grains, though there is a concern that this diet, particularly if done without the guidance of an experienced dietitian, is often deficient in beneficial grains and nutrients. [5] Though the subjects in our study were not asked about gluten-free substitute foods, prior studies have shown that these foods tend to have less folate and iron, and are lower in fiber, than their gluten-containing whole grain counterparts. [6] Still, a gluten-free diet can be compatible with cardiovascular health. Indeed, the increased risk of ischemic heart disease in those with coeliac disease on a gluten-free diet diminishes in the long-term, with an absolute excess risk of only 74 per 100,000 person-years. [7]
With regard to Ms. Wynne’s comment that gluten-free diets may nevertheless contain carbohydrates and sugar, we agree that the complexity of diet makes it difficult to study the isolated effects of one component. In our study, even among those in the lowest quintile of gluten intake, carbohydrates still comprised more than 40% of their caloric sources. Like the study of Wu, et al investigating whole grains, [3] we did adjust for the Alternate Healthy Eating Index (a measure of diet quality), and found that this did not change the overall finding that gluten intake is not associated with coronary heart disease. Therefore, this null association is unlikely to be masked by large differences in dietary quality between high and low gluten consumers.
1. Lebwohl, B., et al., Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ, 2017. 357: p. j1892.
2. Aune, D., 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: p. i2716.
3. Wu, H., et al., Association between dietary whole grain intake and risk of mortality: two large prospective studies in US men and women. JAMA Intern Med, 2015. 175(3): p. 373-84.
4. Manheimer, E.W., et al., Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. Am J Clin Nutr, 2015. 102(4): p. 922-32.
5. Ohlund, K., et al., Dietary shortcomings in children on a gluten-free diet. J Hum Nutr Diet, 2010. 23(3): p. 294-300.
6. Thompson, T., Folate, iron, and dietary fiber contents of the gluten-free diet. J Am Diet Assoc, 2000. 100(11): p. 1389-96.
7. Ludvigsson, J.F., et al., Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation, 2011. 123(5): p. 483-90.
Competing interests: No competing interests
Dear Sir.
We challenge the conclusions of the recent study by Lebwohl, et al (1) which reported that while long-term dietary gluten consumption in people without coeliac disease may not be related to heart disease risk, "the avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk." Their statements, which have led to a rapid spread of misinformation on social media, can be challenged from several perspectives.
Firstly, although the conclusions of the authors may appear compatible with the results of recent meta-analyses, they failed to mention that not all studies reported a clear association between cereals and cardiovascular risk.(2) Furthermore, in some studies, the associations were primarily due to a higher intake of other foods such as fruits, especially citrus, cruciferous vegetables, nuts, or occurred only in men. Moreover, randomized controlled trials (RCTs), which are usually considered to provide evidence on a cause-effect relation, on whole-grain intake and risk markers of diseases have provided less consistent results.(3,4) Interestingly, in one of the first RCTs, there was no evidence of any benefit of increased cereal fibre intake and mortality was somewhat higher although not statistically significant.(5)
Secondly, despite the biological plausibility of the protective effect of cereals on risk of cardiovascular diseases, there are many potential mechanisms through which cereals may act on individual risk factors. In this regard, the authors overlooked that it is possible to get plenty of fibre and various important nutrients from gluten-free grains, such as brown rice, corn, oats, sorghum, millet or pseudo-cereals like amaranth, buckwheat, quinoa. Also, in addition to fibre, many other potentially beneficial compounds within high fibre non-cereal foods, such as antioxidants, hormonally active lignans, phytosterols, amylase inhibitors and saponins could be responsible for their health benefits.
Thirdly, the authors overlooked the low prevalence of cardiovascular diseases in some societies that are 'horticultural' and rely on roots and tubers, as opposed to cereal grains. Indeed, studies in Okinawans, Kitavans, South American Tsimane, whose diets are based on sweet potatoes, plantain, manioc, and only small amount of rice or corn are reported to have extremely low prevalence of cardiovascular diseases.(6,7) Moreover, Okinawan seniors not only have the highest life expectancy in the world, but also the highest health expectancy. However, the traditional diets of these societies underwent „Westernisation“ i.e. an increase consumption of sugar, cereals, processed foods and, in the case of Okinawans, „Japanisation“ (an increase in white rice). All these changes are thought to be the cause of remarkable health deterioration. A typical example is the South Pacific island of Western Samoa, which saw a dramatic explosion of the prevalence of obesity and non-insulin dependent diabetes mellitus, associated with high leptin concentrations.(8)
Fourthly, it has been suggested that some environmental factors specific to agrarian societies could initiate diseases of affluence in the above mentioned societies. Although there are many such candidate environmental factors, cereals seem to be the clearest defining dietary difference between an agrarian and non-agrarian diet. As for the constituent(s) of cereals causing leptin resistance as a sign of insufficient adaptation, Jönsson et al (9) propose lectins such as wheat germ agglutinin as a candidate with sufficient properties. Indeed, several lines of evidence suggest that cereal lectins could cause leptin resistance either indirectly, through effects on metabolism central to the proper functions of the leptin system, and/or directly, through binding to human leptin or leptin receptor, thereby affecting the function.(9)
Fifthly, the hypothesis that an agrarian diet could initiate diseases of affluence was tested in prospective diet interventions comparing Paleolithic diet with non-agrarian diets. These studies have shown beneficial effects of Paleolithic diet comprising lean meat, fruits, vegetables and nuts, and excluding food types, such as dairy, legumes and cereal grains, compared with other healthy diets, on various health markers. A recent systematic review and meta-analysis, where these studies were included, showed that a Paleolithic diet improves some components of the metabolic syndrome more than guideline-based control diets.(10) Another systematic review and meta-analysis concluded that the Mediterranean diet with education decreased HbA1c more than control diets but not more than the Palaeolithic diet with education.(11)
Finally, the absence of cardiovascular benefit of strict gluten-free diet observed in study by Lebwohl et al.(1) can be explained by other factors. For example, it is generally agreed that even among patients with celiac disease up to 60% are partially non-adherent (12). Moreover, individuals following a gluten free diet because of gluten sensitivity or another health-related reason were found to have significantly lower dietary adherence than those diagnosed with celiac disease as defined by the Biagi et al dietary adherence score.(13) It is also important to note that some foods such as fish and rice, consumed by people on gluten free diet have high concentrations of metals such as arsenic, mercury, lead, cadmium, and cobalt and the association between these metals and cardiovascular disease has been recognised for years as highlighted in a recent review by Lamas et al.(14)
In summary, the current ethnographic, epidemiologic and prospective data suggest that a well-balanced gluten-free diet should not necessarily put people without coeliac disease at a higher risk for cardiometabolic diseases. Indeed, hominins consumed a grain-free diet from 2.6 million years ago to about 12,000 years ago (15), so it is highly unlikely that a gluten-free diet or Paleolithic diet is going to kill anyone long-term. In fact, grains are not essential, and contain no nutrient that cannot be obtained from other plant foods. Thus, it can be safely concluded that, whether gluten-free diet is indicated or not, it is not detrimental to avoid gluten. However, it is also important to note that recent scientific findings are beginning to lend support to a new approach to diet, science-backed "personalised" approaches to dietary recommendations. Available data warrant additional evaluations of the risks and benefits of gluten avoidance among specific groups of non-celiac population.
Michal R. Pijak, MD
Kristina Szantoova, PhD
Jan Vyjidak, LLM. MSc.
References
1. Lebwohl B, Cao Y, Zong G, et al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 2017;357:j1892. doi: 10.1136/bmj.j1892.
2. 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. doi: 10.1136/bmj.i2716.
3. Brownlee IA, Moore C, Chatfield M, et al. Markers of cardiovascular risk are not changed by increased whole-grain intake: the WHOLEheart study, a randomised, controlled dietary intervention. Br J Nutr. 2010 Jul; 104(1): 125–134. doi: 10.1017/S0007114510000644
4. Tetens I. Substituting whole grain for refined grain: what is needed to strengthen the scientific evidence for health outcomes? Am J Clin Nutr 2017;105:545-46. doi:10.3945/ajcn.117.152496.
5. Burr ML, 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;2:757-61. doi:org/10.1016/S0140-6736(89)90828-3.
6. Lindeberg S, Söderberg S, Ahrén B, Olsson T. Large differences in serum leptin levels between nonwesternized and westernized populations: the Kitava study. J Intern Med. 2001;249:553-8. doi:10.1046/j.1365-2796.2001.00845.x
7. Kaplan H, Thompson RC, Trumble BC et al. Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet 2017;389(10080):1730-1739. doi: 10.1016/S0140-6736(17)30752-3.
8. Zimmet P, Hodge A, Nicolson M, et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ 1996; 313: 965–9. doi:.org/10.1136/bmj.313.7063.965.
9. Jönsson T, Olsson S, Ahrén B, Bøg-Hansen TC, Dole A, Lindeberg S. Agrarian diet and diseases of affluence--do evolutionary novel dietary lectins cause leptin resistance? BMC Endocr Disord. 2005;10:5-10 doi: 10.1186/1472-6823-5-10.
10. Manheimer EW, van Zuuren EJ, Fedorowicz Z, Pijl H. Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. Am J Clin Nutr 2015;102:922–32. doi: 10.3945/ajcn.115.113613.
11. Carter P, Achana F, Troughton J, Gray LJ, Khunti K, Davies MJ. A Mediterranean diet improves HbA1c but not fasting blood glucose compared to alternative dietary strategies: a network meta-analysis. J Hum Nutr Diet 2014;27:280–97. doi: 10.1111/jhn.12138.
12. Hall NJ, Rubin G, Charnock A. Systematic review: adherence to a gluten-free diet in adult patients with coeliac disease. Aliment Pharmacol Ther. 2009;30(4):315-30.
13. Biagi F, Bianchi PI, Marchese A, et al. A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life. Br J Nutr. 2012 Nov 28;108:1884-8.
14. Lamas GA, Navas-Acien A, Mark DB, Lee KL. Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy. J Am Coll Cardiol. 2016;67:2411-8. doi: 10.1016/j.jacc.2016.02.066.
15. Eaton SB, Konner MJ, Shostak M. Stone Agers in the Fast Lane: Chronic Degenerative Diseases in Evolutionary Perspective. Am J Med. 1988;84:739–49.
Competing interests: No competing interests
What the authors fail to address is that going gluten-free is not the same as going sugar-free or carbohydrate-free; gluten-free bread, pizza, cookies, etc. still contain carbohydrates and sugars, which cause increased insulin levels, weight gain, type 2 diabetes, coronary heart disease, etc. What, exactly, did the participants eat as their entire diet during this study? It seems there are too many variables to draw the conclusion that the authors came to.
Competing interests: No competing interests
Dear Editor,
Lebwohl et al. [1], articulately describe why gluten free diets among people without coeliac disease should be discouraged, since this could result in reduced consumption of whole grains, which may in turn affect cardiovascular risk. However, this should not undermine the importance of a gluten free diet for people with coeliac disease whereby the ingestion of gluten not only results in villous damage but increases the risk of malabsorption, anaemia, osteoporosis and slight increase in malignancies. [2]
At a time when prescriptions of gluten free products are under review it is essential to consider the impact this would have on people with coeliac disease. Our own research based on data collected in the West Midlands (in press) revealed that there was significantly (P<0.001) better adherence to a gluten free diet by patients who received gluten free food on prescription compared to patients who did not (n=143). Furthermore work by Hall et al. [3] has shown that intentional gluten consumption was significantly lower in people who received gluten free food on prescription.
Although the current trends for a gluten free diet in people without coeliac disease is ill advised, prescriptions for gluten free food for people with coeliac disease remain key for dietary adherence and managing short and long term symptoms of the disease.
References
1. Lebwohl, B, Cao Y, Zong G, Hu FB. Green HR et al. (2017), Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 2017;357:j1892
2. Mooney P, Hadjivassiliou M, Sanders DS. Clinical review—coeliac disease. BMJ 2014;348:g1561.
3. Hall NJ, Rubin GP, Charnock A. Intentional and inadvertent non-adherence in adult coeliac disease. A cross-sectional survey. Appetite 2013; 356: 56-62. doi:10.1016/j.appet.2013.04.016 pmid:23623778.OpenUrl
Competing interests: The authors have previously received a Dr Schar Institute Nutrition Award
Letter to the editor,
Recently, I read an article entitled “Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study”[1]. This prospective cohort study was performed by Lebwohl B et al with 26 years of follow-up. I have some questions about this prospective cohort study. Firstly, how do authors perform follow-up, by coming to visit, making telephone, and online contact or other? In addition, there is no loss of follow-up in such a large sample size? How to ensure no loss to follow-up? I hope authors can answer these questions.
Competing interests: No competing interests.
References:
1. Lebwohl B, Cao Y, Zong G, et al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 2017;357 doi: 10.1136/bmj.j1892[published Online First: Epub Date].
Competing interests: No competing interests
Re: Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study
Dear Editor, I could not understand the narrowness of this research. The conclusion that cutting gluten out of the diet could leave a person short of nutrients, for instance, is simply not true. There are other grains and seeds which are full of nutrients, without the risks of gluten. Amaranth, millet, quinoa, hemp seeds, pumpkin seeds, linseeds, etc. I bake linseed bread , make porridge from amaranth, quinoa, millet and sultanas, and use millet and parsnip or courgette to create a potato-free 'mash'.
I have a deep interest in nutrition/ health and am gluten and dairy intolerant. If I eat gluten - wheat, barley, oats, rye - I bloat and feel extremely uncomfortable, developing acid reflux. If I eat dairy I suffer diarrhoea, wind, my asthma worsens and joint s ache. When I gave these things up my health improved. Gluten-free baked goods - cakes, bread - are often full of sugar and other simple carbohydrates and often create a similar response in me.
Competing interests: No competing interests