Low Grade Inflammation and Diet

Key messages

• There is reasonable level of evidence from 13 observational studies for an association between diets high in whole grains and lower levels of the inflammatory marker CRP.
• There is limited evidence to indicate legumes may be beneficial in reducing low-grade inflammation.
• There is evidence of an association between dietary fibre intake and lower levels of the markers of low-grade inflammation.
• Studies suggest a positive relationship between higher consumption of refined grains and inflammatory diseases and inflammatory markers.
• Whole grains may reduce low grade systemic inflammation by mediating insulin resistance, promoting weight loss or via antioxidant activity of naturally occurring key nutrients and phytochemicals.  
• Fibre is thought to reduce inflammatory marker concentrations by mediating insulin resistance and promoting weight loss.

Background

Low grade inflammation, also known as meta-inflammation or subclinical inflammation, is an immune system response to stimuli causing elevated pro-inflammatory markers in the bloodstream. In the hours following the consumption of a meal, there is an elevation in the concentrations of inflammatory markers in the bloodstream. However, in obese people and those with chronic disease these high levels of inflammation persist in a constant state. Low grade inflammation is different to acute/chronic inflammation where the latter is generally a response to high injury and trauma.

Researchers suggest, that just as the germ theory of the 19^th Century helped us understand the case and spread of infectious disease, low grade inflammation may be the key feature underpinning a wide range of chronic diseases which plague the modern era – including type 2 diabetes and depression to heart disease, many forms of cancer, and even dementia.¹ Consequently markers of low grade inflammation are beginning to be used as markers of chronic disease risk and are the targets of treatment.

Studies have established an association between lifestyle factors including diet and systemic inflammation. Among the components of a healthy diet, whole grains, vegetables, fruit, and fish are all associated with lower inflammation.² However, proponents of the paleo diet and low carbohydrate diets suggest including grains in the diet results in a state of low grade inflammation, increasing risk of chronic disease.

What does the literature say?

Markers of low grade inflammation

Markers of low grade inflammation include C-reactive protein (CRP) and fibrogen which are markers of cardiovascular disease as well as interleukins and tumour necrosis factor alpha, indicators of higher risk of metabolic disorders including obesity and Type 2 diabetes.

Relationship between dietary whole grains, key nutrients and low grade inflammation

Evidence indicates whole grains and high fibre grains may be protective against low-grade inflammation.

A review of epidemiological and intervention studies on the effect of whole grain on low-grade inflammation concluded there is a reasonable level of evidence from 13 observational studies for an association between diets high in whole grains and lower CRP concentrations. However, the same review found intervention studies do not demonstrate a clear effect of increased whole grain consumption on CRP or other markers of inflammation. This may be explained by inconsistencies in the research methodologies in the five identified studies.³

Diets higher in refined grains, processed meats and fried foods are linked to higher levels of inflammatory markers.⁴ Studies conducted by Masters et al and Lu et al, showed that frequent consumption of refined grains  increased  the release of pro-inflammatory markers as opposed to a diet higher in whole grains.^5,6 Similarly Liu et al reported an association between an increase in high glycemic loads and an increase in C- reactive protein, likely due to a diet high in refined foods.⁷

A review by Galisteo et al. of the effects of dietary fibre on metabolic syndrome outlines the evidence for the effect of fibre on inflammation.⁸ The review reports that an association between dietary fibre intakes and reduced levels of inflammatory markers has been shown in people with diabetes, hypertension or obesity, and an even stronger relationship among people with two or more of these conditions of metabolic syndrome.⁹ Two cross sectional studies and one longitudinal study indicate an association between dietary fibre intake and reduced CRP levels.^10,11 A study of diabetic women found the intake of both cereal fibre, whole grains and bran to be associated with lower levels of CRP and TNF-α receptor 2 .⁶

Intervention trials on dietary fibre also indicate a beneficial effect on proinflammatory and anti-inflammatory cytokines and adipocytokines in adipose tissue. In one study IL-18 concentration decreased after consumption of a high-carbohydrate high-fibre meal (16.8 g fibre) in both healthy subjects and those with diabetes.¹² Another study of 120 women followed for 2 years on a low energy Mediterranean-style diet including a higher intake of fibre (25 vs. 16 g/day in the control group) exhibited serum concentrations of proinflammatory markers IL-6, IL-18 and CRP.¹³

Relationship between dietary legumes and low grade inflammation

A meta-analysis of 17 intervention trials with a total of 2,300 people found the Mediterranean diet, characterised by high consumption of legumes, is linked to significantly increased levels of anti-inflammatory markers and significant decreases in anti-inflammatory markers.¹⁴

However a second meta-analysis of nine randomised controlled trials on the effects of legumes specifically (other than soy beans) on CRP found only a non-significant trend for the reduction of CRP with increasing legume intake. However, the study design appears to affect the results so more studies are needed to confirm the effect.¹⁵

There is no significant evidence of an effect of soy on low-grade inflammation. A review published in 2009 of 14 trials on soy foods found no significant effect on markers of inflammation.¹⁶ One large scale cohort study has reported an association between soy isoflavones and reduced CRP.¹⁷

Mechanism

Low-grade inflammation is a characteristic of the obese state, as obese people have higher circulating concentrations of many inflammatory markers than lean people. These markers are thought to play a role in causing insulin resistance and other metabolic disturbances. 

Higher intakes of whole grains are associated with reduction in body fat and improved insulin sensitivity, both of which are linked to reduction in inflammatory markers. It is proposed that the effect of whole grains is also likely to mediated through reduction in oxidative stress.¹⁸ Whole grains contain a range of compounds which may promote anti-inflammatory actions, preventing cellular oxidation and systemic inflammatory responses.^18,19  These inclue the phyto-chemicals lignin and phyto-oestrogen as well as the nutrients vitamin E, selenium, zinc, magnesium and folate.

Phyto-chemicals in whole grains including lignans and phyto-sterols, are thought to act as antioxidants by preventing free radical damage to cells and tissues which induce an inflammatory response.²⁰ Higher intakes of magnesium has been shown in two large studies to be linked to reduced likelihood  of inflammation.^21,22 Folate, found in whole grains, has a role in folate-homocysteine regulation⁷ which in turn mediates  the release of inflammatory proteins.²³

It has been suggested that the association between insoluble fibre intake and reduced risk of chronic disease may be explained in part by modulation of inflammatory markers. The effect of fibre may be as a result of aiding weight loss which is known to reduce inflammation, as a result of the role of fibre in modulating glycemic response or the production of butyrate as a result of fermentation in the gut.⁸

The proponents of grain avoidance suggest that grains induce inflammation by increased post-pradial insulin response which leads to fat deposition and consequently increase in inflammatory markers. In the hours following the consumption of a meal, there is an elevation in the concentrations of inflammatory mediators in the bloodstream, which is exaggerated in obese subjects and in type 2 diabetics. Both high-glucose and high-fat meals may induce postprandial inflammation.² However, it is the quality of grain food choices that is important. Whole grain, high fibre and low GI grains reduce post-prandial glycemic response and therefore insulin levels.

Conclusion

The consumption of whole grains and high fibre grains is linked to reduced low-grade inflammation which may be part of the explanation for the reduced risk of chronic disease that results from a diet high in these foods. It is thought that the protective effect of whole grains and high fibre grains is as a result of the naturally occurring vitamins, minerals, fibre and phytochemicals which play a role in anti-inflammatory mechanisms.

References

1. van Woudenbergh GJ, Theofylaktopoulou D, Kuijsten A, et al. Adapted dietary inflammatory index and its association with a summary score for low-grade inflammation and markers of glucose metabolism: the Cohort study on Diabetes and Atherosclerosis Maastricht (CODAM) and the Hoorn study. The American journal of clinical nutrition. 2014.
2. Calder PC, Ahluwalia N, Brouns F, et al. Dietary factors and low-grade inflammation in relation to overweight and obesity. The British journal of nutrition. 2011;106 Suppl 3:S5-78.
3. Lefevre M, Jonnalagadda S. Effect of whole grains on markers of subclinical inflammation. Nutrition reviews. 2012;70(7):387-396.
4. Defagó MD, Elorriaga N, Irazola VE, Rubinstein AL. Influence of Food Patterns on Endothelial Biomarkers: A Systematic Review. The Journal of Clinical Hypertension. 2014;16(12):907-913.
5. Masters RC, Liese AD, Haffner SM, Wagenknecht LE, Hanley AJ. Whole and Refined Grain Intakes Are Related to Inflammatory Protein Concentrations in Human Plasma. The Journal of nutrition. 2010;140(3):587-594.
6. Qi L, van Dam RM, Liu S, Franz M, Mantzoros C, Hu FB. Whole-Grain, Bran, and Cereal Fiber Intakes and Markers of Systemic Inflammation in Diabetic Women. Diabetes care. 2006;29(2):207-211.
7. Liu S, Manson JE, Buring JE, Stampfer MJ, Willett WC, Ridker PM. Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. The American journal of clinical nutrition. 2002;75(3):492-498.
8. Galisteo M, Duarte J, Zarzuelo A. Effects of dietary fibers on disturbances clustered in the metabolic syndrome. Journal of Nutritional Biochemistry.19(2):71-84.
9. King DE, Mainous AG, Egan BM, Woolson RF, Geesey ME. Fiber and C-Reactive Protein in Diabetes, Hypertension, and Obesity. Diabetes care. 2005;28(6):1487-1489.
10. King DE, Egan BM, Geesey ME. Relation of dietary fat and fiber to elevation of C-reactive protein. American Journal of Cardiology.92(11):1335-1339.
11. Ajani UA, Ford ES, Mokdad AH. Dietary Fiber and C-Reactive Protein: Findings from National Health and Nutrition Examination Survey Data. The Journal of nutrition. 2004;134(5):1181-1185.
12. Esposito K, Nappo F, Giugliano F, et al. Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus. The American journal of clinical nutrition. 2003;78(6):1135-1140.
13. DJ J. Lente carbohydrate: a newer approach to the dietary management of diabetes.  . Diabetes care. 1982;5:7.
14. Schwingshackl L, Hoffmann G. Mediterranean dietary pattern, inflammation and endothelial function: A systematic review and meta-analysis of intervention trials. Nutrition, Metabolism and Cardiovascular Diseases. 2014;24(9):929-939.
15. Salehi-Abargouei A, Saraf-Bank S, Bellissimo N, Azadbakht L. Effects of non-soy legume consumption on C- reactive protein: a systematic review and meta-analysis. Nutrition.
16. Beavers KM, Jonnalagadda SS, Messina MJ. Soy consumption, adhesion molecules, and pro-inflammatory cytokines: a brief review of the literature. Vol 672009.
17. Nicastro H, Mondul A, Rohrmann S, Platz E. Associations between urinary soy isoflavonoids and two inflammatory markers in adults in the United States in 2005–2008. Cancer Causes & Control. 2013;24(6):1185-1196.
18. Jacobs DR, Andersen LF, Blomhoff R. Whole-grain consumption is associated with a reduced risk of noncardiovascular, noncancer death attributed to inflammatory diseases in the Iowa Women's Health Study. The American journal of clinical nutrition. 2007;85(6):1606-1614.
19. Jensen MK, Koh-Banerjee P, Franz M, Sampson L, Grønbæk M, Rimm EB. Whole grains, bran, and germ in relation to homocysteine and markers of glycemic control, lipids, and inflammation. The American journal of clinical nutrition. 2006;83(2):275-283.
20. Slavin JL, Jacobs D, Marquart LEN, Wiemer K. The Role of Whole Grains in Disease Prevention. Journal of the American Dietetic Association. 2001;101(7):780-785.
21. Song Y, Ridker PM, Manson JE, Cook NR, Buring JE, Liu S. Magnesium intake, C-reactive protein, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes care. 2005;28(6):1438-1444.
22. King DE, Mainous AG, 3rd, Geesey ME, Woolson RF. Dietary magnesium and C-reactive protein levels. Journal of the American College of Nutrition. 2005;24(3):166-171.
23. Andersson A, Tengblad S, Karlström B, et al. Whole-Grain Foods Do Not Affect Insulin Sensitivity or Markers of Lipid Peroxidation and Inflammation in Healthy, Moderately Overweight Subjects. The Journal of nutrition. 2007;137(6):1401-1407.

Add years to life with fibre

Ask anyone why they should eat fibre and they’ll likely tell you to ‘help keep me regular’. But there are many more reasons to eat a high fibre diet including new evidence of it promoting longer life.

In recent months, with three independent meta-analyses of cohort studies being published in close succession, the academic flood gates have opened on the relationship between dietary fibre and longevity.

Two meta-analyses, published in the American Journal of Epidemiology in 2014, each pooling the data from approximately 1 million people found that compared to people eating the lowest amounts of fibre each day (15 grams per day), those eating the highest intakes (27 grams per day) had a significantly lower risk of  early death from any cause.^{(1, 2)}  Researchers of one of these studies translated the effect as a 23% reduction in risk of a premature death for people eating the highest fibre intakes.⁽¹⁾

Uniquely, the researchers of the first paper (Kim, et al) also analysed the data from these high quality studies to investigate whether different fibres (e.g. fibre from grains, vegetables or fruits) offered greater protection against an early death. They found fibre from grain foods and vegetables were significantly linked with a reduced risk of death and in comparison grains offered the greatest protection.⁽¹⁾ The researchers also found favourable effects on longevity with higher intakes of fibre from legumes such as beans; however this was only based on one study which reported the relationship between fibre from legumes and risk of death. 

This supports findings from the European Prospective Investigation Into Cancer and Nutrition cohort (EPIC)⁽³⁾ that some fibre rich foods may be more protective than others. Within the European countries included in the EPIC cohort study the main source of total fibre varies within each population, however the countries with the strongest associations linking fibre intake with reduced risk of death were observed in the Danish and Greek cohorts, which had the highest percentages of fibre from grain foods and vegetables (56% and 16%, respectively, in Denmark and 29% and 36%, respectively, in Greece). As a comparison, Australia’s most recent National Nutrition Survey showed grains foods were the leading source of dietary fibre followed by vegetable and fruits contributed (44%, 19% and 15% respectively).⁽⁴⁾

Most recently, a further meta-analysis published in Molecular Nutrition Food Research in January took this comprehensive investigation a step further and looked not only at fibre intake and risk of death, but also the risk of death from specific diseases such as cancers and heart disease. This paper pooled data from over 1.7 million people from around the world and found that compared with the lowest fibre consumers, the highest consumers had a 23% reduced risk of death from heart disease and a 17% lower risk of death from cancer.⁽⁵⁾

How does fibre protect health?

As higher fibre intakes have been linked with a reduced risk of weight gain, type 2 diabetes, some cancers and heart disease it makes sense that that a higher fibre diet also translates to a longer life. Some potential mechanisms for the protective nature of higher fibre diets include:^{(1, 2, 5)}:

• Promoting a healthy weight, through reduced energy intake and increased satiety
• Improving blood glucose responses after eating a meal  
• Decreasing cholesterol levels
• Lowering levels of inflammation  
• Promoting a healthy bacteria population in the digestive system, which in turn produce health promoting components (i.e. short-chain fatty acids)
• Lowering blood pressure

Despite the ability to add years to life and life to years with higher fibre intakes, most Australians are falling short of fibre recommendations; females (19 years and  over) eating an average of 21 grams each day (25 gram recommendation) and males eating 25 grams each day (30 grams recommendation). As such, the majority of Australian fibre intakes are nowhere near the targets for people to reduce risk of chronic disease (28 grams each day for women and 38 grams for men).

In addition to inadequate fibre intakes, a survey commissioned by the Grains & Legumes Nutrition Council (GLNC) in 2014 found that on average two in three people did not identify grain foods such as rolled oats, wholemeal breads, wholemeal pasta, brown rice or muesli as being a source of fibre.⁽⁶⁾ On the other hand, three out of four respondents to GLNC’s survey identified fruit and vegetables as a source of dietary fibre however only one in three people identify legumes foods such as kidney beans, baked beans, chickpeas, split peas, soy beans and lentils as containing dietary fibre.⁽⁶⁾ Given grains are Australia’s leading source of dietary fibre, this apparent lack of awareness of the important nutrition contribution of grain foods is concerning. In light of the recent ‘anti-grain’ messages which flooded the media via proponents of low carbohydrate diets, people may be inadvertently cutting out fibre rich grain foods and legumes to the detriment of their health and longevity.  In respect to legumes specifically, with less than 5% of Australians reporting they ate legumes on the day before the most recent National Nutrition Survey these fibre rich foods such as beans, lentils, chickpeas and peas; which deliver around 5 grams per serve (75g or half a cup cooked) have huge potential to help Australians achieve a higher fibre diet and improve health.

Boosting fibre intakes

When it comes to fibre, the evidence is clear that small changes can make a huge difference over the life span. In fact each of the recent studies concluded that every 10 gram increase in total daily fibre intake is linked with a reduced risk of an early death by at least 10%.^{(1, 2, 5)} These findings add to the already compelling body of evidence which supports dietary guidelines for people to enjoy a wide range of fibre rich plant foods each day and to reduce low fibre nutrient poor choices such as cakes, biscuits, confectionery, sweetened beverages and takeaway meals.

As the leading source of dietary fibre, GLNC encourages Australians to make smart grain choices such as enjoying grain foods 3 – 4 times per day with at least half as whole grain or high fibre options. This is an easy first step for Australians to boost their fibre intakes. To further assist Australians in achieving a higher fibre diet GLNC also recommends people eat legumes at least 2 - 3 times each week which is an achievable goal for people to start this healthy habit.

For a range of fibre rich recipes, cooking tips and snack ideas with grains and legumes visit the GLNC website.

References:

1. Kim Y, Je Y. Dietary Fiber Intake and Total Mortality: A Meta-Analysis of Prospective Cohort Studies. American Journal of Epidemiology. 2014;180(6):565-73.
2. Yang Y, Zhao L, Wu Q, Ma X, Xiang Y. Association Between Dietary Fiber and Lower Risk of All-Cause Mortality: A Meta-Analysis of Cohort Studies. American Journal of Epidemiology. 2014.
3. Chuang S-C, Norat T, Murphy N, Olsen A, Tjønneland A, Overvad K, et al. Fiber intake and total and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition cohort. The American Journal of Clinical Nutrition. 2012;96(1):164-74.
4.  ABS. Australian Health Survey: Nutrition First Results - Foods and Nutrients, 2011-12. Australian Bureau of Statistics, 2014.
5. Liu L, Wang S, Liu J. Fiber consumption and all-cause, cardiovascular, and cancer mortalities: A systematic review and meta-analysis of cohort studies. Molecular Nutrition & Food Research. 2015;59(1):139-46.
6. GLNC. 2014 Australian Grains and Legumes Consumption and Attitudinal Report. Unpublished: 2014.

Development of an Australian Whole Grain Database

By Sayne Dalton – Dietitian (APD) and PhD candidate at the Smart Foods Centre, University of Wollongong.

There are many challenges involved in getting consumers to eat more whole grain foods.  Knowing which foods contain whole grains and assisting consumers to identify these foods is part of the challenge.  Then, there is unravelling the science on the health benefits of whole grains and further contributing to the evidence-base by conducting dietary research, on specific population groups.

The development of a comprehensive whole grain database is a critical step in addressing these challenges.  A whole grain database provides information on the whole grain content of foods such as breads and breakfast cereals, which may contain a significant proportion of non-whole grain components, such as refined grains or added sugar.  This information may be used in a number of ways, for example: 

• To assist nutrition professionals to identify and direct consumers to foods higher in whole grain
• To provide a resource for nutritional monitoring of the marketplace and
• To provide data to measure whole grain intakes in dietary studies.

However, until recently there has been no such database available in Australia to assist with these activities.

To address this gap, as part of my PhD at the Smart Foods Centre, University of Wollongong, I developed a whole grain database that provides nutrition practitioners and consumers with information about the types of products containing whole grains in the Australian market and their whole grain content ⁽¹⁾. I applied the database to investigate the whole grain intakes of participants in a dietary trial (results unpublished) and further, to evaluate the whole grain content of food products in the Australian market (results unpublished).

The database is the first of its kind in Australia and one of only a handful in the world that will allow more accurate analysis of whole grain intakes and provide much needed support to research the benefits of whole grains in the diet.

The database was developed by collating data on 385 food products from 46 food companies, with support from the Grains & Legumes Nutrition Council (GLNC), who assisted in facilitating the transfer of the data. There were a variety of products containing whole grains identified in the Australian market. Key foods were raw grains, pasta, breakfast cereals, breads and savoury biscuits. Grain-based foods such as these are important sources of whole grains in the Australian diet and encouraging their consumption aligns with GLNC’s 48 gram whole grain Daily Target Intake⁽²⁾ and the 2013 Australian Dietary Guidelines⁽³⁾.

However, the study suggests that careful food choices are required to assist consumers to identify the most whole grain dense choices. Despite the variety of whole grain products identified in the market, there was marked variation in the whole grain content of products in most food categories. For instance, bread products ranged from 5.1 grams to 70.0 grams whole grain per 100 gram product; whereas, ready-to-eat breakfast cereals ranged from 6.0 grams to 100.0 grams per 100 gram product. The database developed by myself (Sayne Dalton) and colleagues (Prof Linda Tapsell, Dr Yasmine Probst and Assoc. Prof Marijka Batterham)⁽¹⁾ provides a resource for practitioners to identify the types of foods that provide the greatest contribution of whole grain ingredients and complements other tools that assist consumers to identify whole grains at the point-of-purchase; such as the GLNC Code of Practice for Whole Grain Ingredient Content Claims, a voluntary industry standard launched in 2013.

To access a copy of the published article and database click here. To identify whole grain-dense food choices in the supermarket, consumers are also advised to look out for products which are ‘high’ or ‘very high’ in whole grain which will assist Australians in meeting the 48 gram whole grain Daily Target Intake. A full list of products that are registered with GLNC as containing significant amounts of whole grain and aligned to the industry standard can be downloaded from the GLNC website. More information about the GLNC Code of Practice for Whole Grain Ingredient Content Claims may also be accessed from the website.

For further information please contact Sayne Dalton via sct20@uowmail.edu.au.

References

1. Dalton, S.M.C., Probst, Y.C., Batterham, M.J., & Tapsell, L.C., Compilation of an Australian database of manufactured and packaged food products containing wholegrain ingredients. Journal of Food Composition and Analysis, 2014. 36(1-2): p. 24-34.
2. Griffiths T and Nestel P. Developing a target for daily wholegrain intake for Australians. Food Australia. 2006;58(9):431-433
3.  National Health and Medical Research Council.  Australian Dietary Guidelines. 2013. Canberra: National Health and Medical Research Council.
4. National Health and Medical Research Council.  Eat for health.  Australian Dietary Guidelines.  Providing the scientific evidence for healthier Australian diets. 2013. Canberra: National Health and Medical Research Council.