The idea that grains are pro-inflammatory seems to be a ubiquitous belief nowadays. From medical professional friends to lay people to Crossfitter's at the bar (...drinking beer/vodka), I get the question a lot: are grains inflammatory?
Epidemiological evidence overwhelmingly suggest that whole grains, and dietary patterns that include whole grains, like the Mediterranean diet, are either associated with lower circulating markers of inflammation (CRP, IL-6, etc), or have a null effect (1-9). The most recent Nutrition Reviews on the topic concluded that while epidemiological evidence supports a positive effect of whole grains on inflammatory markers, intervention studies don't indicate a clear effect on markers of inflammation, and calls for additional research (10). If you're further interested in epidemiological associations with diet and inflammation, see the most recent Nutrition review (11). Since the Nutrition Reviews publication, a randomized controlled crossover trial came out(12), reporting a positive effect of whole grains on CRP and some adhesion markers adhesion markers during weight loss in obese children. However, the control group in this study, from dietary intake data, appears to have chosen refined grains in place of avoiding whole grains - not answering the begging question of the positive effects of a grainless diet versus one containing whole grains*. Some may point to Paleolithic studies, but I have yet to see one that actually matched macronutrients and/or wasn't performed during some sort of weight loss trial (expected to lower inflammatory markers), to truly isolate the effects of grains - Alan Aragon had a nice comparison table on this in his Paleo diet Powerpoint - see here. The only Paleo diet study I can find that measures CRP (13) is in pigs... This study compared the effects of feeding a pig a varied diet, rich in fruits, vegetables, beef, fish and small amounts of tubers, to pigs fed a diet of entirely cereal grains and rapeseed oil - hardly isolating the effects of grains, modeling human diets or providing any unique support for a Paleo diet. Still, people will cite this to support their cause.
Update*: stumbled onto this study - here - it reports an improvement in IL-6 due to shifts in gut microbe ecology. The study didn't have a non-grain consumer control - an arm that included non-starchy vegetable fibers would've been interesting.
Given the scant strong data on the topic, the notion that grains, whole or not, are inherently inflammatory is far from rooted in strong, causal scientific data. I'm not trying to attack Paleo here, but it can't be denied that their community are the major propagators of this claim. I've actually been trying to piece together the roots of these claims for a while now (between reading Wolf and Cordain and Kresser, etc, it's hard to see a clear, consensus opinion). A paper in Nutrients (note: I'm quite skeptical of papers published here - if they were really game changers, they would've been in any of the ASN journals) ,see here, laid out the theory of grains being pro-inflammatory for us.
As a quick side note, the Nutrients paper has some weird citations. Their citation for a benefit of n6:n3 ratios being related to inflammation links to a paper - see here - about adiposity, inflammation and depression. There's actually very little data to support the need for a reduced n6:n3 ratio and remains largely a theoretical recommendation - see here, and here. You can also find a radio interview where the lead author talks about her feelings that grains are causing disease here.
In summary, the authors of this article gather together a significant amount of in vitro data looking at the effects of gluten and other lectins, such at wheat germ agglutinin (WGA), to propose that these are causing damage to the lining of the intestine, and upregulating zonulin expression to create a 'leaky gut'/increasing intestinal permeability that ultimately plays a role in the development of auto-immune diseases (their language implicates this for both individuals with and without disease). The authors also walk through some animal data suggesting that gluten is involved in the pathogenesis of type 1 diabetes. They then walk through the data on whole grain intake and refined grain intake, and the limited ability of current research to demonstrate a clear role of grains in inflammatory processes. When discussing the health effects of Paleolithic diet, they cite that pig study that I mention above, only simply mentioning that it decreased inflammatory markers compared to a 'cereal-based' diet (making no mention that cereal based diet = grains + oil only diet). They also mention a couple of Paleo studies that have been done: both are in non-healthy populations (1 with ischaemic heart disease patients, the other with T2DM) - and the authors fail to note that the Paleo diets were very poorly matched to their controls, in no way whatsoever isolating the effects of grains. Lastly, they mention the Biesiekierski study looking at gluten in IBS - this has been expounded upon since the publication, identifying FODMAPs as the factor exacerbating IBS, not gluten - see my post on that here.
From reading that publication, one could easily get worked up and start thinking that cereal lectins, particularly from wheat, are causing a whole host of health issues in individuals, related to chronic inflammation. However, much of the evidence cited is from in vitro models, and very little comes from in vivo. I've been reading a lot of these references and finding some major holes in the theory - namely, that the in vitro data exposes cells to WGA at doses humans would never consume and the in vivo data in animal models comes from studies sourcing raw lectin. Luckily, I recently stumbled upon a recent review of wheat lectins and health, in the Journal of Cereal Science (14). The authors walk through several of the claims made about lectins, including the ones in the Nutrients review paper above. Let's look at the claims and their evidence:
1. The authors note the many claims made using in vitro data, and the paucity of in vivo data from humans.
2. The authors note that cooking significantly effects lectin structure and activity. De-husked lentils completely lose their lectin content during cooking (15). In a kitchen setting, cooking of pasta inactivated WGA. Depending on the level of pre-treated processing, the WGA activity of pasta will vary. Matucci et al, 2004 concluded that, if not already inactviated by pre-processing, all activity of WGA will be lost by consumer cooking (16).
3. The authors cite a study by Cordain and one of his students where individuals were fed 50g of wheat germ (80+ slices of bread worth) and no found WGA was detected in the plasma. Not to be too snarky but I find it mildly funny that one of the biggest anti-grain pushers performed this study and only looked at the plasma - given the proposed mechanism of action from animal models fed raw WGA, one would expect the WGA to be found in the other components of the blood (WBCs, platelets, RBCs).
4. The authors note that several have put forth data that implicated WGA in the increasing incidence/pathogenesis of Celiac Disease, but these notions have been struck down by others (17, 18).
5. Some have implicated wheat lectins as contributing to obesity. WGA has been shown to interact with the leptin receptor in vitro. While this is certainly interesting, this lacks clinical data and epidemiological support. WGA would have to be crossing the intestinal barrier, unaffected by processing/heat treatment, and bind to the leptin receptor, preventing the binding of leptin. There isn't data to support that this is happening, and the citation for this is an evolutionary theory paper found here. Leptin resistance has been more causally linked to hypothalmic inflammation (19). For the science back by data on diet and leptin resistance, see here - note that there is no mention of lectins at all in this paper. If WGA was causing leptin resistance, one would expect whole grains to be associated with overweight/obesity, and refined grains to be less so (seeing as the germ has been removed and thus, the wheat germ agglutinin). However, the opposite is seen (20).
6. As I've noted before here, some cancer researchers have looked at lectin intake in a positive light. This data is quite preliminary, however, and largely from in vitro data - I wouldn't get too excited over it.
--I would certainly like to see more data generated regarding dietary lectin intake, from in vivo models, and maybe re-do Cordain's study. However, the notion that wheat lectins are causing a whole host of inflammatory problems in living humans is unfounded.
In addition to the rebuttals of this paper, I'd like to reiterate some points about zonulin and intestinal permeability that I've discussed before. While intestinal permeability has been suggested to play a role in autoimmunity (21), this has not been shown to be causal, intestinal barrier loss can occur through several mechanisms (with or without epithelial cell damage), and loss of intestinal barrier function alone is insufficient to cause disease (as shown by the CA-MLCK transgenic mouse) (30). For those focusing just on zonulin, many factors affect its expression. Obesity associated insulin resistance increases circulating zonulin (22). The intestinal microbiota also affects zonulin expression in a complex manner not fully understood (23, 24). It's been noted that alcohol and NSAIDs increase intestinal permeability, and are not associated with any of the wide claims that alternative practitioners claim are due to a 'leaky gut' (29). The Nutrients paper cites the beneficial effects of Larazotide acetate, a zonulin inhibitor, in animal and human models; however, they don't cite the original paper, they cite a review - the review only cites a proof of concept study; Larazotide acetate failed to affect intestinal permeability in a recent RCT with Celiacs Disease patients (31). For a very critical review of leaky gut, see this review in Clinical Gastroenterology and Hepatology (30) - their conclusion is that a leaky gut is just as likely the effect of a disease as it is the cause, and that no effective therapies currently exist that restore barrier function.
As many try to understand the causes of auto-immunity, there are a few prevailing theories, and the perfect storm might be necessary. For a surprisingly good summary of the data relating to Celiacs and type 1 diabetes, see this NYT article here. In short, the perfect storm includes:
1. Genetic Predisposition - the HLA DQ2 and 8 haplotypes have been identified as predisposing individuals to both development of type 1 diabetes and Celiac's disease. However, 95% of those with this haplotype don't develop Celiacs disease.
2. Gluten, but not how much gluten - Russians, who consume significantly more wheat (of similar varieties) than the Fins, have a rate of celiac disease that is 5x lower.
3. Cleanliness of the environment/total exposure to microbes - An area known as Karelia, bisected by the Finnish-Russian border, has been studied in relation to type 1 diabetes. Whereas the Fins rank #1 in the world for type 1 diabetes, the Karelians have a prevalence 6x lower. Research has linked the Karelians exposure to a variety of microbes back to their lower rates of autoimmune diseases.
4. Intestinal Microbiota - individuals with Celiacs have significantly fewer Bifidobacterium than healthy controls, as well as higher levels of E. coli. E. coli in rats induces greater intestinal permeability. Antiobiotic use has been associated with an increased risk of developing Celiac Disease (28).
5. Breastfeeding - Breastfed infants have greater numbers of Bifidobacterium in their gut. The American Academy of Pediatrics publication supporting Breastfeeding cites a 52% reduction in the incidence of Celiac Disease when infants are consuming breast milk during the timing of gluten introduction - see here.
6. Timing of antigen exposure - Sweden experienced an increase in Celiacs Disease rates after changing guidelines that allowed for gluten introduction directly after weaning. **UPDATE: this theory has taken a recent hit, see here.
----While many of these lines of evidence are suggestive, data can be quite mixed and it's not yet understood exactly how they all interact, and if other factors play into disease development.
Another good discussion of this topic was found in a Today's Dietitian article here. In short, there is a lack of general understanding and a lack of evidence-based practice that dietitians can employ here. And the association of inflammation and autoimmune diseases is a question of which is the chicken and which is the egg. Autoimmune disorders also seem to play together - having one makes you have a higher risk for having another. There are many associations between nutrition and auto-immune disease, very few backed by research. I'm reminded of the animal models linking dairy intake and type 1 diabetes, suggesting that casein was a cause of autoimmunity that lead to pancreatic islet destruction, and we shouldn't be feeding cow's based formulas to infants (25). This theory recently took a hit when a RCT in 2000 HLA genotyped individuals showed that there was no reduction in the incidence of type 1 diabetes using extensively hydrolyzed formulas compared to controls using a conventional cow's milk based formula (26). Multiple Sclerosis, caused by grains if you believe Dr. Perlmutter's Grain Brain, was recently causally linked to Colstridium perfringens, from foodborne exposure (27). It's easy to find a lot of theory and preliminary evidence when it comes to autoimmunity and nutrition, but its hardly clinically ready - I imagine this is quite frustrating for those looking for ways they could've prevented their illness, or maybe reverse it now, and one can begin to understand why alternative theories have become so prevalent.
Our understanding of grains and inflammation is in need of some further research, particularly from RCT's. As of now, the research shows that whole grains may be protective against some markers of inflammation (for those in more inflammatory states), but that grains in general are likely pretty null in their inflammatory effects and modulated by other factors in the diet. Data regarding the role of lectins in inflammation stems largely from in vitro models, and lacks in vivo support. The notion that grains induce a leaky gut is not supported by any causal human data, and in general, there is limited evidence that a leaky gut causes disease. There remains no evidence-based reason that healthy individuals should avoid whole grain consumption (or even occasional refined grain consumption).
For those interested in grain free diets compared to grain containing diets, it'll be a challenge for researchers to determine the make up of the grain free diet - will the calories and macronutrients from grains be matched in the non-grain? If so, will this newly inserted macro- matched food contain any nutrients that might alter an inflammatory response? The study design of this future grain-free trial will be interesting to see.
Further reading about wheat can be found here: "Does Wheat Make us Fat and Sick?"
Julie Jones did a point by point analysis of Wheat Belly - see here.
As always, if you don't want to eat grains, you don't have to. But saying they're inflammatory isn't an evidence-based claim.
1.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821887/
2. http://www.ncbi.nlm.nih.gov/pubmed/17218824
3. http://ajcn.nutrition.org/content/83/6/1440.full
4. http://www.ncbi.nlm.nih.gov/pubmed/17513398
5. http://www.ncbi.nlm.nih.gov/pubmed/17374666
6. http://jama.jamanetwork.com/article.aspx?articleid=199488
7. http://care.diabetesjournals.org/content/29/2/207.long
8. http://www.ncbi.nlm.nih.gov/pubmed/17391554
9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549403/pdf/394_2012_Article_340.pdf
10. http://www.ncbi.nlm.nih.gov/pubmed/22747841
11.http://www.ncbi.nlm.nih.gov/pubmed/23865797
12. http://www.ncbi.nlm.nih.gov/pubmed/24478050
13. http://www.ncbi.nlm.nih.gov/pubmed/17081292
14. http://www.sciencedirect.com/science/article/pii/S0733521014000228
15. http://www.scopus.com/record/display.url?eid=2-s2.0-84887582175&origin=inward&txGid=05BBF860714AB0BB8C1F324986DB2BF3.ZmAySxCHIBxxTXbnsoe5w%3a2
16. http://www.sciencedirect.com/science/article/pii/S095671350300104X
17. http://www.nature.com/ajg/journal/v97/n8/full/ajg2002521a.html
18. http://www.gastrojournal.org/article/S0016-5085(09)01600-X/abstract
19. http://www.ncbi.nlm.nih.gov/pubmed/22522614
20. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0026601/
21. http://physrev.physiology.org/content/91/1/151
22. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0037160
23. http://diabetes.diabetesjournals.org/content/57/10/2555.abstract
24. http://diabetes.diabetesjournals.org/content/62/4/1238.abstract
25. http://www.ncbi.nlm.nih.gov/pubmed/12198602
26. http://jama.jamanetwork.com/article.aspx?articleid=1878718
27. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0076359
28. http://www.biomedcentral.com/1471-230X/13/109
29.http://www.nhs.uk/conditions/leaky-gut-syndrome/Pages/Introduction.aspx
30. http://www.ncbi.nlm.nih.gov/pubmed/23851019
31. http://www.ncbi.nlm.nih.gov/pubmed/23163616
 |
| Source: wellnessmama.com |
Epidemiological evidence overwhelmingly suggest that whole grains, and dietary patterns that include whole grains, like the Mediterranean diet, are either associated with lower circulating markers of inflammation (CRP, IL-6, etc), or have a null effect (1-9). The most recent Nutrition Reviews on the topic concluded that while epidemiological evidence supports a positive effect of whole grains on inflammatory markers, intervention studies don't indicate a clear effect on markers of inflammation, and calls for additional research (10). If you're further interested in epidemiological associations with diet and inflammation, see the most recent Nutrition review (11). Since the Nutrition Reviews publication, a randomized controlled crossover trial came out(12), reporting a positive effect of whole grains on CRP and some adhesion markers adhesion markers during weight loss in obese children. However, the control group in this study, from dietary intake data, appears to have chosen refined grains in place of avoiding whole grains - not answering the begging question of the positive effects of a grainless diet versus one containing whole grains*. Some may point to Paleolithic studies, but I have yet to see one that actually matched macronutrients and/or wasn't performed during some sort of weight loss trial (expected to lower inflammatory markers), to truly isolate the effects of grains - Alan Aragon had a nice comparison table on this in his Paleo diet Powerpoint - see here. The only Paleo diet study I can find that measures CRP (13) is in pigs... This study compared the effects of feeding a pig a varied diet, rich in fruits, vegetables, beef, fish and small amounts of tubers, to pigs fed a diet of entirely cereal grains and rapeseed oil - hardly isolating the effects of grains, modeling human diets or providing any unique support for a Paleo diet. Still, people will cite this to support their cause.
Update*: stumbled onto this study - here - it reports an improvement in IL-6 due to shifts in gut microbe ecology. The study didn't have a non-grain consumer control - an arm that included non-starchy vegetable fibers would've been interesting.
Given the scant strong data on the topic, the notion that grains, whole or not, are inherently inflammatory is far from rooted in strong, causal scientific data. I'm not trying to attack Paleo here, but it can't be denied that their community are the major propagators of this claim. I've actually been trying to piece together the roots of these claims for a while now (between reading Wolf and Cordain and Kresser, etc, it's hard to see a clear, consensus opinion). A paper in Nutrients (note: I'm quite skeptical of papers published here - if they were really game changers, they would've been in any of the ASN journals) ,see here, laid out the theory of grains being pro-inflammatory for us.
 |
| Source: daimanuel.com |
As a quick side note, the Nutrients paper has some weird citations. Their citation for a benefit of n6:n3 ratios being related to inflammation links to a paper - see here - about adiposity, inflammation and depression. There's actually very little data to support the need for a reduced n6:n3 ratio and remains largely a theoretical recommendation - see here, and here. You can also find a radio interview where the lead author talks about her feelings that grains are causing disease here.
In summary, the authors of this article gather together a significant amount of in vitro data looking at the effects of gluten and other lectins, such at wheat germ agglutinin (WGA), to propose that these are causing damage to the lining of the intestine, and upregulating zonulin expression to create a 'leaky gut'/increasing intestinal permeability that ultimately plays a role in the development of auto-immune diseases (their language implicates this for both individuals with and without disease). The authors also walk through some animal data suggesting that gluten is involved in the pathogenesis of type 1 diabetes. They then walk through the data on whole grain intake and refined grain intake, and the limited ability of current research to demonstrate a clear role of grains in inflammatory processes. When discussing the health effects of Paleolithic diet, they cite that pig study that I mention above, only simply mentioning that it decreased inflammatory markers compared to a 'cereal-based' diet (making no mention that cereal based diet = grains + oil only diet). They also mention a couple of Paleo studies that have been done: both are in non-healthy populations (1 with ischaemic heart disease patients, the other with T2DM) - and the authors fail to note that the Paleo diets were very poorly matched to their controls, in no way whatsoever isolating the effects of grains. Lastly, they mention the Biesiekierski study looking at gluten in IBS - this has been expounded upon since the publication, identifying FODMAPs as the factor exacerbating IBS, not gluten - see my post on that here.
 |
| Source: Paleoparents.com |
From reading that publication, one could easily get worked up and start thinking that cereal lectins, particularly from wheat, are causing a whole host of health issues in individuals, related to chronic inflammation. However, much of the evidence cited is from in vitro models, and very little comes from in vivo. I've been reading a lot of these references and finding some major holes in the theory - namely, that the in vitro data exposes cells to WGA at doses humans would never consume and the in vivo data in animal models comes from studies sourcing raw lectin. Luckily, I recently stumbled upon a recent review of wheat lectins and health, in the Journal of Cereal Science (14). The authors walk through several of the claims made about lectins, including the ones in the Nutrients review paper above. Let's look at the claims and their evidence:
1. The authors note the many claims made using in vitro data, and the paucity of in vivo data from humans.
2. The authors note that cooking significantly effects lectin structure and activity. De-husked lentils completely lose their lectin content during cooking (15). In a kitchen setting, cooking of pasta inactivated WGA. Depending on the level of pre-treated processing, the WGA activity of pasta will vary. Matucci et al, 2004 concluded that, if not already inactviated by pre-processing, all activity of WGA will be lost by consumer cooking (16).
3. The authors cite a study by Cordain and one of his students where individuals were fed 50g of wheat germ (80+ slices of bread worth) and no found WGA was detected in the plasma. Not to be too snarky but I find it mildly funny that one of the biggest anti-grain pushers performed this study and only looked at the plasma - given the proposed mechanism of action from animal models fed raw WGA, one would expect the WGA to be found in the other components of the blood (WBCs, platelets, RBCs).
4. The authors note that several have put forth data that implicated WGA in the increasing incidence/pathogenesis of Celiac Disease, but these notions have been struck down by others (17, 18).
5. Some have implicated wheat lectins as contributing to obesity. WGA has been shown to interact with the leptin receptor in vitro. While this is certainly interesting, this lacks clinical data and epidemiological support. WGA would have to be crossing the intestinal barrier, unaffected by processing/heat treatment, and bind to the leptin receptor, preventing the binding of leptin. There isn't data to support that this is happening, and the citation for this is an evolutionary theory paper found here. Leptin resistance has been more causally linked to hypothalmic inflammation (19). For the science back by data on diet and leptin resistance, see here - note that there is no mention of lectins at all in this paper. If WGA was causing leptin resistance, one would expect whole grains to be associated with overweight/obesity, and refined grains to be less so (seeing as the germ has been removed and thus, the wheat germ agglutinin). However, the opposite is seen (20).
6. As I've noted before here, some cancer researchers have looked at lectin intake in a positive light. This data is quite preliminary, however, and largely from in vitro data - I wouldn't get too excited over it.
--I would certainly like to see more data generated regarding dietary lectin intake, from in vivo models, and maybe re-do Cordain's study. However, the notion that wheat lectins are causing a whole host of inflammatory problems in living humans is unfounded.
In addition to the rebuttals of this paper, I'd like to reiterate some points about zonulin and intestinal permeability that I've discussed before. While intestinal permeability has been suggested to play a role in autoimmunity (21), this has not been shown to be causal, intestinal barrier loss can occur through several mechanisms (with or without epithelial cell damage), and loss of intestinal barrier function alone is insufficient to cause disease (as shown by the CA-MLCK transgenic mouse) (30). For those focusing just on zonulin, many factors affect its expression. Obesity associated insulin resistance increases circulating zonulin (22). The intestinal microbiota also affects zonulin expression in a complex manner not fully understood (23, 24). It's been noted that alcohol and NSAIDs increase intestinal permeability, and are not associated with any of the wide claims that alternative practitioners claim are due to a 'leaky gut' (29). The Nutrients paper cites the beneficial effects of Larazotide acetate, a zonulin inhibitor, in animal and human models; however, they don't cite the original paper, they cite a review - the review only cites a proof of concept study; Larazotide acetate failed to affect intestinal permeability in a recent RCT with Celiacs Disease patients (31). For a very critical review of leaky gut, see this review in Clinical Gastroenterology and Hepatology (30) - their conclusion is that a leaky gut is just as likely the effect of a disease as it is the cause, and that no effective therapies currently exist that restore barrier function.
As many try to understand the causes of auto-immunity, there are a few prevailing theories, and the perfect storm might be necessary. For a surprisingly good summary of the data relating to Celiacs and type 1 diabetes, see this NYT article here. In short, the perfect storm includes:
1. Genetic Predisposition - the HLA DQ2 and 8 haplotypes have been identified as predisposing individuals to both development of type 1 diabetes and Celiac's disease. However, 95% of those with this haplotype don't develop Celiacs disease.
2. Gluten, but not how much gluten - Russians, who consume significantly more wheat (of similar varieties) than the Fins, have a rate of celiac disease that is 5x lower.
3. Cleanliness of the environment/total exposure to microbes - An area known as Karelia, bisected by the Finnish-Russian border, has been studied in relation to type 1 diabetes. Whereas the Fins rank #1 in the world for type 1 diabetes, the Karelians have a prevalence 6x lower. Research has linked the Karelians exposure to a variety of microbes back to their lower rates of autoimmune diseases.
4. Intestinal Microbiota - individuals with Celiacs have significantly fewer Bifidobacterium than healthy controls, as well as higher levels of E. coli. E. coli in rats induces greater intestinal permeability. Antiobiotic use has been associated with an increased risk of developing Celiac Disease (28).
5. Breastfeeding - Breastfed infants have greater numbers of Bifidobacterium in their gut. The American Academy of Pediatrics publication supporting Breastfeeding cites a 52% reduction in the incidence of Celiac Disease when infants are consuming breast milk during the timing of gluten introduction - see here.
6. Timing of antigen exposure - Sweden experienced an increase in Celiacs Disease rates after changing guidelines that allowed for gluten introduction directly after weaning. **UPDATE: this theory has taken a recent hit, see here.
----While many of these lines of evidence are suggestive, data can be quite mixed and it's not yet understood exactly how they all interact, and if other factors play into disease development.
Another good discussion of this topic was found in a Today's Dietitian article here. In short, there is a lack of general understanding and a lack of evidence-based practice that dietitians can employ here. And the association of inflammation and autoimmune diseases is a question of which is the chicken and which is the egg. Autoimmune disorders also seem to play together - having one makes you have a higher risk for having another. There are many associations between nutrition and auto-immune disease, very few backed by research. I'm reminded of the animal models linking dairy intake and type 1 diabetes, suggesting that casein was a cause of autoimmunity that lead to pancreatic islet destruction, and we shouldn't be feeding cow's based formulas to infants (25). This theory recently took a hit when a RCT in 2000 HLA genotyped individuals showed that there was no reduction in the incidence of type 1 diabetes using extensively hydrolyzed formulas compared to controls using a conventional cow's milk based formula (26). Multiple Sclerosis, caused by grains if you believe Dr. Perlmutter's Grain Brain, was recently causally linked to Colstridium perfringens, from foodborne exposure (27). It's easy to find a lot of theory and preliminary evidence when it comes to autoimmunity and nutrition, but its hardly clinically ready - I imagine this is quite frustrating for those looking for ways they could've prevented their illness, or maybe reverse it now, and one can begin to understand why alternative theories have become so prevalent.
Our understanding of grains and inflammation is in need of some further research, particularly from RCT's. As of now, the research shows that whole grains may be protective against some markers of inflammation (for those in more inflammatory states), but that grains in general are likely pretty null in their inflammatory effects and modulated by other factors in the diet. Data regarding the role of lectins in inflammation stems largely from in vitro models, and lacks in vivo support. The notion that grains induce a leaky gut is not supported by any causal human data, and in general, there is limited evidence that a leaky gut causes disease. There remains no evidence-based reason that healthy individuals should avoid whole grain consumption (or even occasional refined grain consumption).
For those interested in grain free diets compared to grain containing diets, it'll be a challenge for researchers to determine the make up of the grain free diet - will the calories and macronutrients from grains be matched in the non-grain? If so, will this newly inserted macro- matched food contain any nutrients that might alter an inflammatory response? The study design of this future grain-free trial will be interesting to see.
Further reading about wheat can be found here: "Does Wheat Make us Fat and Sick?"
Julie Jones did a point by point analysis of Wheat Belly - see here.
As always, if you don't want to eat grains, you don't have to. But saying they're inflammatory isn't an evidence-based claim.
1.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821887/
2. http://www.ncbi.nlm.nih.gov/pubmed/17218824
3. http://ajcn.nutrition.org/content/83/6/1440.full
4. http://www.ncbi.nlm.nih.gov/pubmed/17513398
5. http://www.ncbi.nlm.nih.gov/pubmed/17374666
6. http://jama.jamanetwork.com/article.aspx?articleid=199488
7. http://care.diabetesjournals.org/content/29/2/207.long
8. http://www.ncbi.nlm.nih.gov/pubmed/17391554
9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549403/pdf/394_2012_Article_340.pdf
10. http://www.ncbi.nlm.nih.gov/pubmed/22747841
11.http://www.ncbi.nlm.nih.gov/pubmed/23865797
12. http://www.ncbi.nlm.nih.gov/pubmed/24478050
13. http://www.ncbi.nlm.nih.gov/pubmed/17081292
14. http://www.sciencedirect.com/science/article/pii/S0733521014000228
15. http://www.scopus.com/record/display.url?eid=2-s2.0-84887582175&origin=inward&txGid=05BBF860714AB0BB8C1F324986DB2BF3.ZmAySxCHIBxxTXbnsoe5w%3a2
16. http://www.sciencedirect.com/science/article/pii/S095671350300104X
17. http://www.nature.com/ajg/journal/v97/n8/full/ajg2002521a.html
18. http://www.gastrojournal.org/article/S0016-5085(09)01600-X/abstract
19. http://www.ncbi.nlm.nih.gov/pubmed/22522614
20. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0026601/
21. http://physrev.physiology.org/content/91/1/151
22. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0037160
23. http://diabetes.diabetesjournals.org/content/57/10/2555.abstract
24. http://diabetes.diabetesjournals.org/content/62/4/1238.abstract
25. http://www.ncbi.nlm.nih.gov/pubmed/12198602
26. http://jama.jamanetwork.com/article.aspx?articleid=1878718
27. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0076359
28. http://www.biomedcentral.com/1471-230X/13/109
29.http://www.nhs.uk/conditions/leaky-gut-syndrome/Pages/Introduction.aspx
30. http://www.ncbi.nlm.nih.gov/pubmed/23851019
31. http://www.ncbi.nlm.nih.gov/pubmed/23163616
Great post!
ReplyDeleteThey didn't measure inflammation markers in this new study, but the authors discuss a potential mechanism for why whole-grains could be anti-inflammatory:
«The fermentation of grain fiber takes place in the large intestine, beneficially affecting the composition of gut microbiota and decreasing the permeability of the gut barrier. An improved gut barrier reduces leakage of endotoxic bacterial lipopolysaccharides (LPS) into the circulation. Lower concentrations of LPS in the blood seem to alleviate peripheral inflammation and insulin resistance. The fermentation of grain fiber also leads to a continuous supply and absorption of metabolites, such as short chain fatty acids and ferulic acid derivatives, which may have anti-inflammatory effects and improve insulin resistance.»
http://www.nmcd-journal.com/article/S0939-4753%2814%2900038-6/abstract
Thanks Erik! Interesting paper - there was an ASN presentation (by a rep of General Mills/Whole Grain Council - I forget which one) that also made the claim that grain fiber fermentation provides anti-inflammatory effects. So many theories - need more data!
DeleteYou don't mention Dr. Alessio Fasano by name. But he is an author of the study you mention about zonulin and he's mentioned in the NYT article. I haven't read his book but I watched his YouTube video. He actually says that gluten is toxic to everybody, but few people lose the battle. He might be trying to counter some of those wild claims out there. What I'm understanding him to say is that the everybody's immune system mistakes gluten fragments for bacteria, but we're exposed to bacteria all the time so it doesn't matter for most people. However, it does seems like he is stating as fact that gluten fragments trigger some opening of the tight junctions.
ReplyDeletehttps://www.youtube.com/watch?v=VvfTV57iPUY
Ah yes I've seen a lot of Fasano's work and further seen it misconstrued by Wheat Belly/Paleo folk. His use of the word 'toxic' is a bit strong for me; i think he's just getting at the point that alpha-gliadin residues are seen as foreign by the body, and in some, it is pathogenic. Thanks for sharing the vid - had never seen him speak.
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