Category: Research

Medical Research: Low Fat vs. Low Carbohydrate Diet–Which One Promotes Weight Loss?

The debate between following a low-fat, weight-loss diet and eating to lower carbohydrates and thereby lose weight appears to be settled after a large medical study. Some people, including many ketogenic and paleo dieters, believe cutting back on carbohydrates helps them lose weight. Others, including many physicians and medical centers, promote diets that cut back on saturated fats found in red meats and dairy products, as recommended by the US Department of Agriculture in its Food Pyramid.

food pyramid
The official USDA Food Pyramid

In a 600-person, year-long study, the two eating styles helped dieters drop almost exactly the same number of pounds — and there didn’t seem to be much rhyme or reason as to who succeeded on which plan.

Going into the study, which was published today in the Journal of the American Medical Association, researchers wanted to settle the debate but they also wanted to know if blood insulin levels or genotype had an effect on weight loss.

High blood levels of insulin are a sign of insulin resistance, which often precedes Type 2 diabetes. Many believe high serum insulin promotes storing calories as fat. Researchers looked at the genetic profile of each participant and determined which ones had particular genetic traits thought to lead to weight gain. To the researchers’ surprise, neither genetic predisposition nor high insulin levels had any effect.

Results show you can lose weight with either eating plan

People studied were between 18 and 50 years old, and all overweight or obese but otherwise healthy. They attended nutrition classes taught by a health educator. There were no calorie restrictions. Everyone was directed to minimize their intake of sugars, refined flours, and trans fats. At the same time, they were encouraged to eat vegetables and nutrient-dense foods.  Everyone was encouraged to adopt healthy habits like cooking at home and sitting down for structured meals with family members.

As you would expect, not everyone on the diets lost weight and some had dramatic losses. The outliers were one individual who gained 20 pounds and another who lost 60. However, the average weight loss in each group was almost identical: 11 pounds in the low-fat group, compared to 13 pounds in the low-carb group.

“It’s not so much about that food — it’s really about [changing] this crazy way that Americans eat.”

About 30% of people in the study had a genetic signature that, in theory, should have pointed to success on the low-fat diet, while 40% had a low-carb “profile”. But the data didn’t show any strong similarity between these genetic markers and weight loss on the corresponding diet. Neither did measures of insulin resistance, which the team also thought would be related to success.

The successful dieters, regardless of which group they were in, credited their achievement to a reframed relationship with food. They began eating more mindfully, cooking at home more often and focusing on whole foods instead of processed, packaged foodstuff.

According to the lead researcher, Christopher D. Gardner, Ph.D., “That was more powerful than differentiating between low-carb or low-fat. Just getting them to be a lot more mindful about what they were eating. It’s not so much about that food — it’s really about [changing] this crazy way that Americans eat.”

What about your diet?

These articles may also interest you.

http://aswellasicanbe.com/chronic-illness/maximize-nutrition/

http://aswellasicanbe.com/chronic-illness/a-ketogenic-diet-improves-me-cfs-symptoms/

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Pfizer Pulling Out of AD and PD Research

According to an article published today in Front Line Genomics, drug industry leader Pfizer will no longer pursue research into Alzheimer’s (AD)and Parkinson’s (PD) Diseases. The announcement comes on the heels of several failed trials of their own and other Big Pharma drugs for these devastating conditions.

Pfizer faced a major setback in 2012 when the company and its partner, Johnson & Johnson decided to discontinue the development of bapineuzumab IV following a late-stage failure. Eli Lilly and Company and Merck have also pile of pills

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been unable to develop treatments for Alzheimer’s. Lilly, after disappointing results in a late-stage study, decided in November 2016 to abandon its AD treatment, solanezumab. Merk’s AD potential drug, verubecestat, was halted in the EPOCH Phase II/III study in February 2017 after it was determined the study might fail. Another ongoing study is expected to report out in February 2019. Another drug company, Biogen, suffered a recent setback when it was found its experimental drug did not meet criteria for success.  Axovant Sciences also had a major setback in September 2017 when its AD drug candidate failed to meet the endpoints in a late-stage study.

This leaves people who live with these diseases with only a few new prescription medications in the drug pipeline. Biogen’s aducanumab is in a couple of late-stage studies. Biogen is also working on elenbecestat, a genetics-based drug in a Phase III program in collaboration with Eisai. Lilly has several AD candidates in its pipeline, including lanabecestat, developed with AstraZeneca. Novartis and Amgen are collaborating on a similar genetics-based drug, while Roche is collaborating with AC Immune in the development of AD treatments (Source).

Fortunately, there are recent findings in the areas of natural health for both brain-related diseases. Tai Chi and QiGong improve physical function, depression, and quality of life in people with PD. Coconut oil can help improve brain function in women with AD.

Let me know in the comments below if you would like more information about non-drug treatments for these and other chronic diseases.

 

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The Man Who Changed ME/CFS Treatment Recommendations

This interview with ME/CFS “knight in shining armor who rode to the rescue” was initially posted on Anil Van Der Zee’s eponymous blog.  Anil was born in Sri Lanka and grew up in the north of Holland. He studied classical ballet at the Royal Conservatory in The Hague before working in several ballet companies in the Netherlands and Switzerland. In 2007 he became ill after a viral infection and never fully recover. A few years later he was diagnosed with Myalgic Encephalomyelitis.

David Tuller and the (s)PACE cake eaters

In 2015 David Tuller, DrPH, a Senior Fellow in Public Health in Journalism at the Center of Global Public Health, School of Public Health at Berkeley University started writing 3 very detailed blogs about the flaws of the now infamous PACE-trial. The patient community has been advocating for years, if not decades against these types of trials of Cognitive Behavioural Therapy (CBT) as well as Graded Exercise Therapy (GET) for ME in general as they seem to be doing more harm than good. Unfortunately, they were mostly dismissed as militants and “vexatious”. They were not being heard or believed. That has dramatically changed since Dr. David Tuller started writing extensively about the subject. A real paradigm shift is happening and I’m beyond honored to have been able to meet him, photograph him and ask him a few questions.

David TullerPhoto by Anil Van Der Zee

Hi David, how are you? Thanks for letting me interview you. For the people who are not familiar with the subject, what is the PACE-trial and why is this trial such a big deal?

The PACE trial was the largest study of “treatments” for what the investigators called chronic fatigue syndrome. The investigators claimed it “proved” that CBT and GET were effective treatments for the illness. Given these alleged findings, the trial has had an enormous impact on what is considered the standard of care in the U.K., the U.S, the Netherlands, and many other countries. Yet the study is so flawed, it includes so many violations of core principles of scientific research that its reported findings are completely meaningless.

What was the reason you decided to start writing about the PACE-trial unlike many of your journalist colleagues? Many are reluctant to write about ME in general.

I started reading the patients’ commentaries about PACE and realized that they were right about the flaws in the trial. I understood why others weren’t interested—it’s very confusing to figure the whole thing out. As a journalist, it’s great to have a topic others aren’t covering, and no one was writing about this. I felt if I started looking into it, I could have an impact on the debate.

Could you explain what the main issues were with the PACE-trial?

There were so many issues, so it’s hard to pick just one! Probably the biggest issue is that they have been very explicit in their protocol about how they planned to measure success. But they changed the main outcome measures after collecting data, and all the changes allowed them to report better results than had they stuck to their original methods from the protocol. Then they refused to provide the analyses that they originally promised to provide so no one could tell what the results would have been had they not changed all their outcomes. When patients asked for these anonymous data, the investigators accused them of being “vexatious” and refused. They only did so after being ordered to do so by a legal tribunal.

What were the results of the reanalysis?

The authors themselves published a reanalysis for their measure of what they defined as “improvement.” The published study reported around 60 % “improvement” with CBT and GET. In the reanalysis, only about 20 % “improved” with these therapies, while 10 % “improved” with the comparison arms. That 10 % difference is most likely due to bias because the two therapies include telling patients that these treatments will make them better. Those in the two comparison arms were not told they would get better.

post trial PACE changes

An outside group reanalyzed the findings for “recovery.” They found that the “recovery” rates for the CBT and GET groups fell from 22 % to single digits. The “recovery” rates for the comparison arms were also in the single digits, and there were no statistically significant differences between the groups. In other words, by dramatically weakening their outcomes, they managed to report in the peer-reviewed “recovery” paper that people had “recovered” when in fact no one had, according to their original measures.

What are the biggest flaws in these type of trials? What is wrong with the model that is being used?

The biggest flaw is that they are conducting open-label or non-blinded trials while relying on subjective outcomes—in this case, the outcomes were self-reported questionnaires about physical function and fatigue. An open-label trial means everyone knows what treatment they’re getting. And if the outcomes are subjective, as in this case, they are always subject to significant bias—especially if the treatment arms include telling participants that they will improve with these treatments. In PACE, they had several objective outcomes—whether people got back to work, whether they got off benefits, whether they could walk farther, and whether they were more fit. All these measures failed to match the positive outcomes they reported for the subjective measures. Because of that, they dismissed their own objective measures as irrelevant or not objective after all.

Why have ME and the PACE-trial become so important to you?

I’ve seen the serious negative impact of this trial and its reported results on patients. No one except patients was really taking it on. I thought I could do something to help and demolish the credibility of the trial. I didn’t expect to keep doing this for more than two years, but it became clear that it would take more time and more reporting and more pushing to achieve the desired outcome—which is that the PACE trial and others from this cabal of “experts” are discredited and hopefully retracted.

No one would ever suggest that CBT can lead to “recovery” from Parkinson’s.

Why is ME, according to you, not a psychological illness or a behavioural disorder??

Well, I’m not a clinician or a scientist, so I’m not the one to determine what exactly is causing the illness. It’s just obvious that after 30 years of the CBT/GET paradigm, this approach doesn’t work. The science that is cited to show that it does work is completely bogus—as patients have always known and as I’ve tried to document over the last two years. So in effect, the researchers have disproven their own theory even while claiming their work proves it to be true. On top of that, many very, very smart people have found a host of physiological dysfunctions in patients that make a pretty definitive case that this is not a psychological or behavioral disorder.

CBT and exercise are recommended for other diseases, so why are they so vilified by the patient community and the ME experts?

Patients are not against CBT and exercise per se. CBT is used in many illnesses to help people adapt to their circumstances. And exercise or physical activity—even raising your arm five times from the bed, if that’s what you can do—is important for everyone. Patients object to the form of these approaches when used for ME. The CBT proposed by PACE is premised on the idea that the therapy will alleviate the patient of “unhelpful beliefs” about having an organic disease that gets worse with over-exertion. It’s not the same kind of CBT you get if you have cancer or MS. No one would ever suggest that CBT can lead to “recovery” from Parkinson’s. As far as exercise, it’s the “graded” part that is the problem—the idea that you should keep increasing your activity levels week by week, and that any symptoms are just normal reactions of the body because you’re deconditioned, not a sign that you’re making things worse. But since the core symptom of the illness is not “fatigue” but the relapses patients suffer after over-exerting themselves, then GET is clearly contra-indicated as a treatment.

In the US things are changing. There’s a real paradigm shift happening. Could you elaborate on this?

The U.S. Centers for Disease Control has removed CBT and GET from its recommendations for the illness. That’s a huge change. The NIH is finally spending more money for decent research—although of course not enough. But there is an acknowledgment now that this is a medical disease and that the patients have been poorly served by the longstanding neglect of government agencies. The change is slow and it’s far from enough, but it’s a big shift nonetheless.

quote-first-they-ignore-you-mahatma-gandhi

This is obviously amazing. Huge. Especially knowing your work has been instrumental in helping this movement shifting in the direction that it’s taking and it’s not only in the US. The same is happening in other countries, even in the Netherlands. That must be a fantastic feeling for you?

Yes, definitely. I feel really good about what I’ve done. But of course, others have played instrumental roles as well. I think I was able to help elevate the concerns patients were already expressing to a more prominent level and greater visibility among scientists not involved in the issue. So I sort of bridged a gap between patients and the academic world. Before it was much easier for the PACE team to make it seem like just crazy, anti-science patients were complaining and objecting. Now the conflict is scientists vs. scientists—and that’s a much better place to be. On the basis of the science, they will ultimately lose.

In the Netherlands scientists like Gijs Bleijenberg, Jos van der Meer or Hans Knoop still push CBT and GET as the preferential treatment for ME or rather CFS. They also claim that the PACE-trial was a one-off or that there is actually nothing wrong with it. That there is nothing wrong with the CBT and GET as a whole. Especially with the trials taking place in the Netherlands. Do you agree?

No, of course not. They are just blowing smoke out of their asses. Their studies are as bad as all the others.

So you feel that the Dutch trials, like for example FITNET contain the same flaws as the PACE-trial?

Not all the same flaws, but the basic design flaw is the same. These are mostly open-label trials relying on subjective outcomes. This design will always produce unreliable and biased results. The studies have also shown, with the use of actometers that measure how far someone walks, that the reported benefits from subjective outcomes are not matched by any improvement in this objective measure.

With everything that is currently happening in the US and honestly worldwide it seems very odd that these scientists still keep holding on to these beliefs. As a patient, I sometimes wonder if these Dutch scientists had a little too much space cake. Not the Potato eaters but the space cake eaters. Or in this case, the (s)PACE cake eaters because their claims are completely off. It’s based on smoke and mirrors. Science is moving on.

What do you think is the reason they keep coming up with these claims that are now going against the largest institutes in the world?

The s(PACE)cake eaters.

I think people are easily self-deluded. This is a paradigm shift. Those embedded or invested in the old paradigm will always have trouble giving it up, even in the face of overwhelming evidence. That’s what’s happening here, I think. If you’ve spent decades promoting a certain ideology or belief system, as they have, then acknowledging that this is fatally flawed is an overwhelming blow to their self-identity, ego, and so on. We’re asking these researchers to admit that not only have they been wrong but that their mistakes have harmed many people. That would be difficult for anyone. In that sense, I have some sympathy for them. I mean, not much sympathy, but I understand why what they have to do in order to do the right thing is a very, very difficult thing to do. They will probably keep believing that they were right even as the science tumbles all around them.

The Dutch Health Council is currently deliberating on new criteria and care for people with “CFS”. What would this report need to state in order for you to consider this a success?

It would need to do what the CDC did—remove CBT and GET from the recommended treatments. The problem is that people in health care don’t like to admit that they have nothing to offer. If CBT and GET are removed, then what treatments can take their place? We don’t really have anything yet. So I understand why that’s hard for those involved in making these decisions. Many people feel, well, better to offer something rather than nothing, and they might think these “therapies” are benign, so what’s the harm of keeping them until we have something better? But of course the recommended treatments are not benign, so they need to be removed even if something great isn’t available yet.

Professor Steve Lubet wrote a guest blog on the Virology blog about ME patients being militant. Do you feel ME patients are militant or are they simply fighting for their health and as professor Lubet mentioned are in fact pro-humanity, much like the gay community has battled against psychiatry at some point?

“Militant” can sound negative, but it’s not negative if the militancy is in service of an important cause. Of course, patients should be militant in insisting that they have not gotten the treatment they deserve. They are right to be militant, just as gay people were right to be militant about getting homosexuality removed from the list of psychiatric disorders.

Since you started writing, the discussion has shifted from patients vs.scientists to scientists vs scientists. It seems like portraying patients as militants is rather a distraction from any valid criticism?

Yes, of course, that’s the case. And it’s not just portraying patients as “militant” but as hysterical, crazy, anti-science, harassing, and death-threat-making. Of course, some patients have been so enraged that they might have expressed themselves in ways that we would prefer they hadn’t. But the PACE folks and their admirers have used that meme as a way of dismissing criticism they don’t like. They still try to do that, as Professor Esther Crawley has in her disgraceful presentations, but now it’s clear that this frame of the debate is not accurate.

 

https://youtu.be/6zWnVB_2lUU

In your “Tear it up” talk at the ‘Invest in ME conference 2017’, you mentioned how you always trusted the system almost blindly. How do you feel about that now? Some major scientific journals like the Lancet made some huge mistakes and have not yet cleaned up their act.

Well, I don’t know if I said I trusted the system “blindly”! If I did, I was probably over-emphasizing to make a point. I understood that studies had problems and often needed to be corrected and that various interests obviously would try to steer studies in their favored direction. What has shocked me is confronting an entire medical-academic establishment that absolutely has refused to acknowledge the flaws, no matter how obvious they are. I didn’t realize just how difficult it was to get journals to correct or retract what are clearly bogus findings, by any standard. That has made me much more skeptical about any studies I read.

In the conclusion of the reanalysis of the PACE-trial by Wilshire et al, they said the following: “The claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments.”

Do you feel the medical community has been misled as much as the patients by these types of treatments?

Well, the medical community has certainly been seriously misled. Most doctors don’t have time to read all the studies and patient blogs and correspondence and all that. They see headlines or just get information filtered down through clinical guidelines or recommendations from NICE or the CDC or wherever. They expect to be able to rely on this information as sound. So I don’t blame clinicians who have adopted these approaches based on what they believed was authoritative evidence.

What needs to be done to rectify this?

Changes in clinical guidelines help a lot. The current NICE guidance is up for a full review. When that happens, it will have a big impact. But these organizations also must actively disseminate news of any changes. In the U.S., the CDC has done nothing so far, from what I can tell, to inform clinicians and medical organizations about the change in recommendations. They have been dishonest brokers, and they are still dishonest brokers. Officially, the CDC says it removed CBT and GET because people were “confused” about what the agency meant in recommending them. That’s just bullshit. They won’t admit that they made a mistake, backed the wrong science, and issued terrible recommendations. And as far as I know, they are not proactively reaching out to the organizations and medical centers that continue to recommend CBT and GET.

What are you hoping that will happen next? What should happen next? Where to “PACE” from here?

Getting rid of PACE and the CBT/GET paradigm is a necessary step but won’t make patients better. It will just prevent them from being recommended treatments that can be harmful. The real advances will come when the scientists now researching the physiological parameters are able to narrow in on accurate biomarkers and effective pharmaceutical treatments. I don’t know how long that will take, but certainly, it will be easier if the CBT/GET era is behind us.

David Tuller Pac manPhoto by Anil Van Der Zee. The PACEMAN t-shirt was a present from Anil to David for talking at the Dutch premiere of the documentary Forgotten Plague in Amsterdam.

I want to thank you for taking the time to answer these questions. I also want to thank you for coming to talk at the Dutch première of the Forgotten Plague in 2016 and the screening of Unrest in Leiden 2017. I was not able to attend either event but you were so kind to come and visit me in person at my bedside. I think that I can speak for everyone in the patient community that we are eternally grateful for what you’ve done and for what you’ve accomplished. I don’t think words can describe our gratitude…

Thank you, David Tuller, or how we like to call you by your alter ego superhero name. Thank you PACEMAN!!!

Anil van der Zee

Former professional ballet dancer, teacher, aspiring choreographer & photographer.
Currently life on hold; Myalgic Encephalomyelitis. Blogging out of necessity.

You may also want to read:

ANSRewire helped me get to 80% recovery

People with ME/CFS exhausted at cellular level

How I conquered low energy and leaky gut

 

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Calcium and Vitamin D Do Not Protect Older Adults From Fractures

When I was still practicing it was strongly suggested that everyone who was chronically ill or not take calcium and vitamin D supplements to protect against bone fracture. However, a recent study examining 33 randomized trials involving 51,145 people found there was no benefit to calcium supplements at all when it came to hip or spine fractures.

According to the study released in the December 26, 2017, issue of the Journal of the American Medical Association, it didn’t matter if the calcium still life with milksupplements contained Vitamin D or not. The number of hip and spine fractures was statistically similar for people on calcium pills and those who did not take the supplement.

Researchers looked at randomized clinical trials comparing calcium,  vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fractures. The study covered community-dwelling adults older than 50 years. They did not look at people in nursing homes, hospitals, and other facilities. The results were the same regardless of gender, dietary calcium, or a previous history of fractures.

Institute of Medicine Report

The main issue is how to obtain sufficient calcium to keep bones strong and prevent osteoporosis. In 2010, the Institute of Medicine (IOM) published recommendations for dietary calcium and vitamin D following a rigorous examination of the studies on potential
health outcomes. The IOM found that the evidence supported a role for these nutrients
in bone health but not in other health conditions. Further, the IOM noted there is emerging
evidence that too much of these nutrients may be harmful. The recommendations recognized conflicting messages about other benefits of these nutrients—especially vitamin D—and also about how much calcium and vitamin D people need to be healthy.

As North Americans take more supplements and eat more of foods that have been fortified with vitamin D and calcium, it becomes more likely that people consume high amounts of these nutrients. Kidney stones have been associated with taking too much calcium from dietary supplements. Very high levels of vitamin D (above 10,000 IUs per day) are known to cause kidney and tissue damage (Source).

Not enough calcium in diets

Most Americans do not get enough calcium and vitamin D in their diets. Consequently, many foods are fortified with calcium and/or vitamin D. Dietary calcium can be obtained in dairy products and leafy greens. Small amounts of vitamin D are found in fatty fish, but most of our vitamin D comes from sunlight. Combining calcium-fortified foods with supplements that can contain upwards of 1,000 mg may lead to kidney damage from excess calcium. The upper limit for calcium in men and women older than 50 is 2,000 mg/day. Vitamin D upper limits for the same group is 4,000 units/day (Source).

Vitamin D is not really a vitamin but instead is a hormone produced by a reaction to sunlight.  It has many different roles in the body related to bones, cancer, heart disease, diabetes, immune function and reproductive health (Source).

People with concerns about this study, especially those who have been diagnosed with osteoporosis, should not stop taking their calcium supplements before speaking with their healthcare provider.

You may also want to read:

http://aswellasicanbe.com/chronic-illness/differences-in-chronic-illness-between-older-and-younger-people/

http://aswellasicanbe.com/chronic-illness/is-functional-medicine-a-viable-alternative/

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Diet and Nutrition Therapy for Chronic Illness

This is the second of a two-part post that first appeared on GreenMedInfo.com. Information about the author follows the references. If you missed the first post, read it at http://aswellasicanbe.com/chronic-illness/fight-autoimmune-diseases/

 

A Low Lectin Diet As a Therapeutic Intervention for Autoimmune Disease

In effect, researchers propose that minimizing intake of lectin-rich food substrates can lessen the persistent antigenic stimulation that results in defective immunological tolerance and causes the immune system to target the body itself (Source). Immunological tolerance is essentially the ability of the immune system to discriminate self from non-self, which is lost with autoimmune disorders (Source). This is also the rationale behind therapeutic regimens such as the paleo diet and autoimmune paleo protocol.

Whereas acute lectin toxicity in humans is insidious, manifesting with symptoms such as nausea, abdominal distention, vomiting, and diarrhea, “In experimental animals fed on diets containing plant lectins the evident symptoms are a loss of appetite, decreased body weight and eventually death” (Source). Therefore, a disease resulting from the effects of lectins can be long-latency, incubating in a sense for many years or decades before culminating in a life-threatening disorder. Thus, it is difficult to correlate symptoms with lectins, and many people may not make a connection between their health issues and the foods they are eating.

A Healthy Dose of Skepticism: More Research is Required

A well-warranted criticism of lectin science and the paleo community is that the foundations of their anti-nutrient arguments are based on animal and in vitro (cell culture) studies, which may not be fairly extrapolated to human physiology. On a ladder representing evidentiary quality, where meta-analyses and systemic reviews are positioned at the top, these study designs occupy lower rungs, are oftentimes found to be methodologically inadequate, and may not predict human reactions (Source).

Many of the studies upon which paleo advocates hang their hats are rodent models, where laboratory animals are fed disproportionately large levels of lectins or lectins from raw legumes, which may not be applicable to human health (Source). The lectin soybean agglutinin (SBA) is commonly cited as inducing intestinal permeability in paleo circles, yet piglet models have shown that disturbed barrier function only occurs when SBA is included at high levels in their diets (Source). Thus, a dose-response relationship may occur and a threshold may be reached beyond which lectin consumption is not tolerated. In addition, some of these same animal models, in fact, reveal that lectin toxicity is reduced by inclusion of oligosaccharides and simple sugars such as sucrose, which naturally occurs in the diet, given the specificity of lectins for carbohydrate moieties (Source).

Also commonly demonized is the peanut lectin, which has been shown in cell culture studies to disrupt the cytoskeletal (filaments and tubules) organization of intestinal tight junctions and lead to intestinal permeability, a phenomenon which may account for the increased allergenicity of peanuts. Paleo champions recommend avoidance of peanuts due to their atherogenic effects in animal models, yet human trials demonstrate that peanuts may improve cardiovascular risk, illustrating that animal studies may not be generalizable to human physiology (Source).

Another point with merit is that many foods included on the paleo diet, such as avocado, banana, beetroot, blackberries, broccoli, Brussels sprouts, cabbage, cantaloupe, carrots, cauliflower, cherries, cucumber, garlic, grapes, leek, mushrooms, mustard, oregano, parsley, peach, pomegranate, potato, pumpkin, taro, tea, tomato as well as various spices and nuts have all been demonstrated to exhibit lectin activity (Source)(Source). This underscores the need to distinguish between lectins and potentially toxic lectins, as the latter may predict poor physiological responses, with the immunostimulatory and gut barrier compromising effects of prolamins and agglutinins being implicated as some of the worst.

Moreover, lectin content varies, and some lectins are relatively innocuous since they are denatured by cooking (Source). Other studies, however, suggest that some lectins are not neutralized with cooking, so researchers have not yet arrived at firm conclusions in this respect. Historically, many ancestral practices, such as soaking and sprouting grains, treating corn with lye, eliminating the hull and bran of brown rice to consume the lower lectin white rice, or peeling and de-seeding vegetables, became intuitive cultural rituals in order to minimize lectin consumption. However, most of us in the industrial age have abandoned these practices and adopt mono-diets where so-called anti-nutrient rich foods are ingested in excess. Soaking, sprouting, and cooking nuts and beans, as well as fermenting vegetables, have been similarly elucidated to decrease the content of phytates, another much-maligned anti-nutrient (Source).

However, whether these approaches have scientific merit is still hotly contested. A recent randomized, cross-over trial challenges the validity of these preparation techniques and concluded not only that soaking did not improve gastrointestinal tolerance, but flatulence ratings were higher for all points for soaked nuts compared to unsoaked. Moreover, the researchers state, “Recommendations to soak nuts prior to consumption to reduce phytate concentrations and improve gastrointestinal tolerance have received much attention in the popular press. This is despite no supporting scientific evidence for the practice” (Source).

Bioindividuality May Dictate Vulnerability to Anti-Nutrients

One reason lectins may pose a problem for some individuals but not others is due to genetic variability in the cell surface glycoconjugates (carbohydrates covalently linked with other chemical species) to which lectins attach, and due to the fact that the glycoprotein tips to which lectins bind are hidden behind sialic acid molecules (Source). However, this protective screen of sialic acid molecules can be removed by the enzyme neuraminidase that accompanies pathogens such as influenza and streptococci, which cause the flu virus and Strep throat, respectively (Source). In fact, this explains the ability of infections to induce or exacerbate autoimmune disease: “This facilitation of lectins by micro-organisms throws a new light on postinfectious diseases and makes the folklore cure of fasting during a fever seem sensible” (Source).

The prevailing gut ecology may also influence susceptibility to the adverse effects of lectins. For instance, the red kidney bean lectin PHA is lethal for rats when administered in high doses, but non-toxic in germ-free animals devoid of a microbiome (Source). These findings suggest that the toxic effects of PHA could be mediated by its ability to enhance navigation of gut bacteria into systemic circulation (Source).

The centrality of the microbiota to food reactions is also applicable to another anti-nutrient frequently cited in the paleo community, phytic acid. Also known as phytate, the storage form of phosphorus in plants analogous to phosphorus in animals, phytic acid is often cited as another reason why grains and beans are excluded from a paleo diet. Phytates have been observed to bind to and inhibit absorption of minerals such as calciumzinc, and magnesium (Source). However, phytates have also been demonstrated to elicit paradoxical hormetic effects, having antioxidant, anticancer, anti-inflammatory, and anti-osteoporotic activity (Source).

Also neglected is the fact that the commensal microbes that inhabit the gut synthesize phytase, an enzyme that degrades phytate, in a dose-dependent manner (Source). In someone with dysbiosis, however, a condition applicable to almost anyone with chronic illness, this ability may be compromised. Much of the reaction to anti-nutrients may, therefore, be contingent upon the functional medicine pillar of biochemical individuality, which is a confluence of genetic proclivities, microbial terrain, environmental stressors, and the prevailing landscape of the body.

When to Implement a Low-Lectin Diet

While some lectins such as WGA and gluten are unequivocally inflammatory in most cases of chronic illness, the science on lectins is far from settled. For example, lectins may exhibit beneficial hormetic effects, as some studies reveal that lectins induce apoptosis and autophagy (self-devouring) of cancer cells, modulate endocrine and immune function, and serve as metabolic signals for the gut.

However, because of the detriment to quality of life incurred by autoimmune disorders, a therapeutic trial of a low-lectin dietary regimen like the paleo or autoimmune paleo diet is deserving of consideration. While there is a paucity of high-quality peer-reviewed human studies, the clinical experience of countless physicians supports the efficacy of these interventions. In addition, data is accruing in favor of these dietary interventions for cardiometabolic conditions and autoimmune diseases, which is further described in my article “Landmark Study Suggests Efficacy of Autoimmune Paleo Protocol”.

The success of these dietary protocols may not only be attributed to their eschewal of immunogenic foods, but also to their inclusion of bioavailable nutrients. According to the hierarchy of healing practiced by naturopathic doctors, less invasive, low-risk modalities should be attempted first when possible according to the therapeutic order, a philosophy with which dietary strategies such as these are compatible.

Researchers echo the aforementioned sentiments, with: “Although it is common knowledge that some dietary lectins can adversely affect the growth and health of young animals…it has not been rigorously established that findings with animals are also directly applicable to humans. However, because the glycosylation state of the human gut is basically similar to that of higher animals, it may be confidently predicted that the effects of dietary lectins will have similarities in both humans and animals” (Source). Self-experimentation through an elimination diet is the gold standard for identifying reactions to food constituents, and lectins are no exception.


References

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39. Kritchevsky, D., Tepper, S.A., & Klurfeld, D.M. (1998). Lectin may contribute to the atherogenicity of peanut oil. Lipids, 33(8), 821-823.

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

Fight Chronic Illness and Autoimmune Diseases with Diet

Are recommendations to avoid grains and legumes due to anti-nutrient content predicated in science or founded in fear mongering? An evidence-based analysis of the good, the bad, and the ugly when it comes to lectins, phytates and autoimmune disease recently appeared in GreenMedInfo. Due to the length of this evidence-based article, I broke it up. Another section, this one on diet for chronic illness, will be posted tomorrow.

Written by: Ali Le Vere, B.S., B.S. – Senior Researcher-GreenMedInfo

In the past decade, some paleo diet proponents have popularized the notion that anti-nutrients, or compounds in foods which undermine health, are responsible for the prevailing epidemics of chronic illness. In fact, one of the fundamental tenets of the paleo diet, that grains contribute to disease and degeneration, is due in part to arguments about their content of lectins, some of the most infamous anti-nutrients. This review will serve as a preliminary examination of the evidence and will shed light on whether fears about this and another commonly vilified anti-nutrient, phytic acid, are groundless or justified.

Lectins: A Self-Survival Mechanism

Lectins are ubiquitous carbohydrate-binding proteins, present in almost a third of our food supply, which constitutes an adaptive mechanism that plants evolved to confer protection against predation and pests. For instance, lectins act as effective biological agents against insect attack by destabilizing insect metabolism, interfering with enzyme activity, and disturbing the protective, digestive, and secretory functions of the gut (1). Due to their insecticide properties, “insect-resistant plants produced by expression of lectin genes in transgenic plants are already a reality,” which is cause for alarm due to the potential health hazards posed by artificially manipulating lectin content.

Lectins act as agglutinins, or sticky proteins, which cause particles to coagulate and form aggregate masses. While most concentrated in seeds, uncooked beans in bowlother vegetative tissues such as barks, bulbs, flowers, leaves, roots, and rhizomes also contain lectins . Two of the best-characterized families of plant-derived lectins are the leguminous lectins and cereal lectins, which is the impetus for their exclusion by paleo diet adherents due to their high levels of prolamins and agglutinins, two types of lectins which are purported to most adversely affect the barrier function of the gut. Solanaceae lectins, which occur in the nightshade vegetables potatoes and tomatoes, are also excluded on the more restrictive autoimmune paleo (AIP) protocol.

Digestive Impairments Due to Lectins

When consumed, lectins survive digestion and bind to carbohydrate moieties of cells lining the gastrointestinal tract, triggering deleterious local or systemic reactions in the animal that ingested the lectin-containing food (Source). By binding to cell surface sugars on the intestinal mucosa, lectins can interfere with stomach and intestinal architecture, and damage the luminal (inward-facing) membranes of the epithelial cell lining (Source). As a result, “Lectins may induce changes in some, or all, of the digestive, absorptive, protective or secretory functions of the whole digestive system and affect cellular proliferation and turnover” (Source).

For instance, lectin-induced changes to intestinal morphology can cause loss of brush border digestive enzymes, required for breaking down food, accelerate cell loss, and create irregularities in the microvilli, or the tiny hairlike projections from intestinal cells that increase absorptive surface area (Source). Cumulatively, these adverse changes impede carbohydrate and protein utilization and transport, which inhibits the growth of the organism (Source). As a compensatory countermeasure, trophic effects can occur, or an abnormal increase in the volume of the intestine due to cellular hyperplasia (Source).

The secretion of gastric acid, required for protein digestion, is also inhibited in some animal models due to lectins attaching to mucosal and parietal cells in the stomach, which generate hydrochloric acid. For example, lectins can result in incomplete proteolytic degradation of immune-stimulating dietary proteins, as evidenced by the ability of the lectin phytohaemagglutinin (PHA) from red kidney beans to decrease the hydrolysis of the dairy protein casein as well as bovine serum albumin.

Importantly, lectins from legumes and cereal grains, for example, can disrupt the integrity of the tight junctions which regulate trafficking of molecules across the gut barrier, causing intestinal hyperpermeability, the gateway to all autoimmune disorders. In other words, lectins can cause the spaces between cells lining our intestines to become excessively leaky and allow the entry of foreign immune-provocating agents. Violation of gut barrier integrity invites bacteria, dietary components, and toxins into systemic circulation.

Microbiome Alterations Due to Lectins

Due to its effects on epithelial cell metabolism, lectins have been demonstrated to result in dramatic overgrowths in coliform bacteria, and Escherichia coli (E. coli) in particular. Lectins also preferentially increase the growth of Lactobacillus lactis, which is associated with the development of rheumatoid arthritis along with E. coli. The lectin PHA from red kidney bean can provide increased levels of substrates upon which E. coli grow due to “PHA-mediated mucus secretion, epithelial cell loss, serum protein leakage and reduced digestion of dietary protein,” all of which serve as nutrient sources that promote bacterial replication (Source). In animal models, lectins also cause severe atrophy of the thymus, the organ where some immune cells mature, which could compromise the cell- and antibody-mediated immune responses that normally keep gut bacteria in check (Source).

This proliferation of bacteria may, in turn, promote overproduction of bacterial toxins such as lipopolysaccharide (LPS), the outer wall from gram-negative bacteria that are implicated in insulin resistance, metabolic syndrome, polycystic ovarian syndrome (PCOS), non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiovascular disease. Also relevant is that the resultant dysbiosis, or bacterial imbalance, that can occur due to lectin ingestion is a causative factor in autoimmune and allergic disorders, metabolic diseasegastrointestinal conditions such as Crohn’s disease and ulcerative colitis, and neuropsychiatric illnesses. Altering the commensal flora of the digestive tract can modulate the immune system in an unfavorable direction since the majority of the immune system interfaces directly with the gut.

Immune Derangements Due to Lectins

After binding to cells of the small intestine known as enterocytes, lectins are internalized at high rates via a process called endocytosis, where a part of the cell membrane invaginates (buds inward) and engulfs material (Source). Once present in the peripheral tissues, lectins can deposit in distant tissues and organs, promoting their enlargement or atrophy, disrupting macronutrient metabolism, and altering hormonal balance (Source). Lectins that translocate across the gut wall can also be perceived by the resident sentinel cells in the gut-associated lymphoid tissue (GALT) called macrophages, which present lectins to other immune cells called lymphocytes and evoke an immune response (Source).

Moreover, lectins can penetrate systemic circulation via regional lymph nodes and bind to glycoproteins (sugar-proteins) on diverse tissues such as that of the pancreas, thyroid, liver, kidney, nasopharynx, pituitary, eye, heart, breast, adrenal glands, myelin sheath, intestines, blood vessels, lymphatic system, cartilage or collagen (Source). This creates a neo-antigen which is perceived as a foreign entity by the immune system, potentially eliciting an immune attack. When self-tissue is caught in the crossfire of the immune response, tissue-specific autoimmune diseases manifest (Source).

Lectins stimulate the immune system via mechanisms such as T-cell proliferation, which expands the pool of autoreactive white blood cells, up-regulation of cell signaling molecules called inflammatory cytokines, which perpetuate tissue damage and recruit more inflammatory immune cells, and production of Th17-cells, which drive tissue destruction in autoimmunity (2). Similarly, lectins are known to incite release of histamine from basophils, as well as interleukin-4 (IL-4) and IL-13, which are instrumental in transitioning to a Th2-centered immune response favoring allergy and other atopic diseases such as asthma (Source).

The immune response is amplified as undigested food particles, bacterial toxins, and pathogenic byproducts that translocate across the gut barrier secondary to lectin-induced gut permeability also incite antibody production, which can, in turn, cross-react with human tissue that possesses similar amino acid sequences (Source). In this way, an immune attack against invading bacterial and food antigens can lead to the development of autoimmune disease via a process called molecular mimicry. This occurs as a result of homology, or similarity, between lectin-bound tissue and motifs (amino acid sequences) on these ‘invading’ substances which are the target of immune response (Source).

Gluten and Wheat Germ Agglutinins: Particularly Harmful Lectins for Autoimmune Disease

While the jury is still out on some lectins, the lectin wheat germ agglutinin (WGA)may be particularly problematic for health for a multitude of reasons. Humans consuming wheat germ exhibit biologically intact wheat germ agglutinin (WGA) in both their ileostomy effluent and fecal collections, indicating the ability of lectins to persist within the gut lumen (Source).

WGA has an affinity for N-acetyl glucosamine, an essential signaling molecule and structural component of the extracellular matrix of animal cells (Source). WGA also binds to the sialic acid called N-glycolylneuraminic acid (Neu5Ac) found at the terminal position of the surface-exposed sugars that comprise the glycocalyx, a fuzz-like coating on the plasma membrane of epithelial cells in the gut that plays a role in cell recognition, adhesion, and communication. Diets high in wheat, which contain the potent lectin WGA, have been shown to cause changes in the mucosal architecture of the jejunum, the middle portion of the small intestine, even in normal subjects (Source). This lectin not only causes leaky gut syndrome, jeopardizing the barrier function of the gut, but it also enables cellular entry of WGA and provokes a pro-inflammatory immune response (Source).

Gluten, on the other hand, is a mixture of prolamin lectins present in wheat, rye, barley, and oats which are evolutionarily conserved proteins that share similar ancestral origins. Prolamins are proline-rich storage proteins in plants that function in germination and are resistant to protease-mediated digestion in the human gastrointestinal tract (Source). Not only are human digestive enzymes incompatible with prolamin degradation, but prolamins also contain protease inhibitors which impair our digestive capacity. Examples of prolamins are gliadins in wheat, hordeins in barley, secalins in rye, and avenins in oat.

loaf of bread
Is bread, the staff of life, bad for you?

However, because gluten-reactive immune cells that react to gliadin, hordein, and secalin do not react to epitopes in avenin, oats are classified as inherently “gluten-free” for celiac patients. Other studies, however, have shown that consumption of oats is pathogenic in one of ten celiac patients, and the potential for gluten cross-contamination of oats is high (Source).

Gluten is particularly detrimental in autoimmune disease since it triggers the release of the intestinal peptide zonulin, which regulates the tight junctions between cells in the gastrointestinal epithelium in a manner that is rapid, reversible, and reproducible (Source). Studies have demonstrated that intestinal exposure to gliadin [the protein sub-fraction of gluten] leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability” in all individuals, not just celiac patients with active disease and in remission, but in patients with non-celiac gluten sensitivity (NCGS) and in non-celiac healthy controls (Source).

Leaky Gut Syndrome

Induction of pathologic intestinal hyperpermeability, or leaky gut syndrome, via zonulin release, is prerequisite for the development of autoimmune diseases such as rheumatoid arthritis, Hashimoto’s thyroiditis, lupus, ulcerative colitis, Type one diabetesGrave’s diseasevitiligo, Crohn’s disease, Addison’s disease, pernicious anemia, multiple sclerosis, and psoriasis. In fact, researchers state that “The autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier function” (Source).

Translocation of gluten-related peptides into the body secondary to so-called leaky gut syndrome are perceived by the gut-associated lymphoid tissue (GALT), the part of the immune system surrounding the gut. This induces innate and adaptive immune responses that can result in the production of pro-inflammatory signaling molecules which perpetuate the breach in the gut barrier and recruit more inflammatory immune cells. Eventually, these immune responses can cause “friendly fire” against our own body tissues, resulting in autoimmune disease, by processes such as the bystander effect or cross-reactivity between foreign antigens and our own tissues (Source).

Celiac disease results in increased infiltration of immune cells and villous atrophy, flattening the shag carpet of the intestines into Berber, and leading to nutrient malabsorption, chronic diarrhea, weight loss, and other adverse sequelae (Source). However, the empirical diagnosis of gluten sensitivity or NCGS is serious in its own right. NCGS can incite not only gastrointestinal symptoms but extra-intestinal manifestations such as ataxia, neuropathy, encephalopathy, autism, and mood disturbances including anxiety, depression, schizophrenia, and psychosis (Source).

This is a lot of highly detailed information for people with brain fog to take in at one reading! 🙂 Please let me know in the comments below if this is too technical and I will translate future articles like this.

Part Two will be posted tomorrow.

Additional reading:

Maximizing nutrient absorption from foods