Do dietary lectins cause disease?

I’m lifting this wholesale from the NCBI site because it’s one of the more reliable articles on lectins and as it dates back to 1999, it seems to be mostly off the radar. My emphasis added.

In 1988 a hospital launched a “healthy eating day” in its staff canteen at lunchtime. One dish contained red kidney beans, and 31 portions were served. At 3 pm one of the customers, a surgical registrar, vomited in theatre. Over the next four hours 10 more customers suffered profuse vomiting, some with diarrhoea. All had recovered by next day. No pathogens were isolated from the food, but the beans contained an abnormally high concentration of the lectin phytohaemagglutinin. Lectins are carbohydrate binding proteins present in most plants, especially seeds and tubers like cereals, potatoes, and beans. Until recently their main use was as histology and blood transfusion reagents, but in the past two decades we have realised that many lectins are (a) toxic, inflammatory, or both; (b) resistant to cooking and digestive enzymes; and (c) present in much of our food. It is thus no surprise that they sometimes cause “food poisoning.” But the really disturbing finding came with the discovery in 1989 that some food lectins get past the gut wall and deposit themselves in distant organs. So do they cause real life diseases?This is no academic question because diet is one part of the environment that is manipulable and because lectins have excellent antidotes, at least in vitro. Because of their precise carbohydrate specificities, lectins can be blocked by simple sugars and oligosaccharides. Wheat lectin, for example, is blocked by the sugar N-acetyl glucosamine and its polymers. These natural compounds are potentially exploitable as drugs should lectin induced diseases be identified.

Wheat gliadin, which causes coeliac disease, contains a lectin like substance that binds to human intestinal mucosa, and this has been debated as the “coeliac disease toxin” for over 20 years. But coeliac disease is already managed by gluten avoidance, so nothing would change were the lectin hypothesis proved. On the other hand, wheat lectin also binds to glomerular capillary walls, mesangial cells, and tubules of human kidney and (in rodents) binds IgA and induces IgA mesangial deposits. This suggests that in humans IgA nephropathy might be caused or aggravated by wheat lectin; indeed a trial of gluten avoidance in children with this disease reported reduced proteinuria and immune complex levels.

Of particular interest is the implication for autoimmune diseases. Lectins stimulate class II HLA antigens on cells that do not normally display them, such as pancreatic islet and thyroid cells. The islet cell determinant to which cytotoxic autoantibodies bind in insulin dependent diabetes mellitus is the disaccharide N-acetyl lactosamine, which must bind tomato lectin if present and probably also the lectins of wheat, potato, and peanuts. This would result in islet cells expressing both class II HLA antigens and foreign antigen together—a sitting duck for autoimmune attack. Certain foods (wheat, soya) are indeed diabetogenic in genetically susceptible mice. Insulin dependent diabetes therefore is another potential lectin disease and could possibly be prevented by prophylactic oligosaccharides.

Another suspect lectin disease is rheumatoid arthritis. The normal human IgG molecule possesses carbohydrate side chains, which terminate with galactose. In rheumatoid arthritis much of the galactose is missing, so that the subterminal sugar—N-acetyl glucosamine—is exposed instead. These deficient IgG molecules feature strongly in the circulating immune complexes that cause fever and symptoms. In diet responsive rheumatoid arthritis one of the commonest trigger foods is wheat, and wheat lectin is specific for N-acetyl glucosamine—the sugar that is normally hidden but exposed in rheumatoid arthritis. This suggests that N-acetyl glucosamine oligomers such as chitotetraose (derived from the chitin that forms crustacean shells) might be an effective treatment for diet associated rheumatoid arthritis. Interestingly, the health food trade has already siezed on N-acetyl glucosamine as an antiarthritic supplement.

Among the effects observed in the small intestine of lectin fed rodents is stripping away of the mucous coat to expose naked mucosa and overgrowth of the mucosa by abnormal bacteria and protozoa. Lectins also cause discharge of histamine from gastric mast cells, which stimulates acid secretion. So the three main pathogenic factors for peptic ulcer—acid stimulation, failure of the mucous defence layer, and abnormal bacterial proliferation (Helicobacter pylori) are all theoretically linked to lectins. If true, blocking these effects by oligosaccharides would represent an attractive and more physiological treatment for peptic ulcer than suppressing stomach acid. The mucus stripping effect of lectins also offers an explanation for the anecdotal finding of many allergists that a “stone age diet,” which eliminates most starchy foods and therefore most lectins, protects against common upper respiratory viral infections: without lectins in the throat the nasopharyngeal mucus lining would be more effective as a barrier to viruses.

But if we all eat lectins, why don’t we all get insulin dependent diabetes, rheumatoid arthritis, IgA nephropathy, and peptic ulcers? Partly because of biological variation in the glycoconjugates that coat our cells and partly because these are protected behind a fine screen of sialic acid molecules, attached to the glycoprotein tips. We should be safe. But the sialic acid molecules can be stripped off by the enzyme neuraminidase, present in several micro-organisms such as influenzaviruses and streptococci. This may explain why diabetes and rheumatoid arthritis tend to occur as sequelae of infections. This facilitation of lectins by micro-organisms throws a new light on post-infectious diseases and makes the folklore cure of fasting during a fever seem sensible.

Alternative medicine popularisers are already publishing articles about dietary lectins, often with more enthusiasm than caution, so patients are starting to ask about them and doctors need to be armed with facts. The same comment applies to entrepreneurs at the opposite end of the commercial spectrum. Many lectins are powerful allergens, and prohevein, the principal allergen of rubber latex, is one. It has been engineered into transgenic tomatoes for its fungistatic properties, so we can expect an outbreak of tomato allergy in the near future among latex sensitive individuals. Dr Arpad Pusztai lost his job for publicising concerns of this type (20 February, p 483).

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In the end, Only Calories Count: Wrong

I’ve been seeing this headline a lot lately:

Diets That Reduce Calories Lead to Weight Loss, Regardless of Carbohydrate, Protein or Fat Content

Well yes that’s true. But quite frankly, it misses the point.

A person who is overweight does not have a weight problem. She has a weight symptom. Her problem is hunger.

There is no point trying to manage weight if you do not manage hunger. There is only so long you can fight your body’s desire to reach and maintain its target weight. And by target I don’t mean the one you have for yourself that makes you look good in a bathing suit. It’s the one your body feels is necessary given your diet composition, your level of activity and your genetic propensity for fat and sugar regulation.
 

Most people don’t know why they are overweight.

They think they know why but they don’t.

The standard answer from patient and doctor alike is “over-eating” which tells you absolutely nothing. I’m here to tell you that there is no such thing as over-eating short of the kind that leaves you feeling unwell because you’ve surpassed the volume comfortable for your stomach.

Over-eating, in the most common sense, refers to any food consumption that precedes weight gain. It’s a tautology. All things being equal, if two people follow the exact same diet and one gains weight, he is said to have “over-eaten” while the other “ate in moderation.” It’s like saying the tree was green because it was green.

The goal of any weight-loss diet should not simply be to create a caloric deficit, but to adopt sustainable lifelong eating habits which make it easy to reach and maintain an ideal weight. That is not to suggest it will ever be easy to drop detrimental eating habits which have been acquired over a lifetime and are probably central to one’s eating culture. But the changes must be sustainable physiologically.

Skinny people may admonish fat ones for failing to show self control, but the fact is that a modern diet makes some people constantly hungry. Fighting that kind of psychological torture day-in day-out is not possible. Gross caloric deficits can be sustained for short periods of time but falling off the wagon is inevitable unless hunger is addressed.

So it is true that the macro-nutrient composition of a diet is irrelevant if you are simply trying to achieve a caloric deficit.

However it is completely relevant if you are trying to control hunger in order to achieve a sustained depletion of fat stores.

Genes remember sugar hit

Just because your blood sugar normalises 8 hours later, it doesn’t mean that cupcake is done with you:

Human genes remember a sugar hit for two weeks, with prolonged poor eating habits capable of permanently altering DNA, Australian research has found.

A team studying the impact of diet on human heart tissue and mice found that cells showed the effects of a one-off sugar hit for a fortnight, by switching off genetic controls designed to protect the body against diabetes and heart disease.

"We now know that chocolate bar you had this morning can have very acute effects, and those effects can continue for up to two weeks," said lead researcher Sam El-Osta, from the Baker IDI Heart and Diabetes Institute.

"These changes continue beyond the meal itself and have the ability to alter natural metabolic responses to diet," he told Australian Associated Press Friday.

Regular poor eating would amplify the effect, said El-Osta, with genetic damage lasting months or years, and potentially passing through bloodlines.

The study’s findings were reported in the Journal of Experimental Medicine.

Source: Yahoo Australia

Brain Enzyme a Factor in Weight Loss

More research on our rodent friends who by now should have every mechanism worked out in order that they stay slim.

Blocking a particlar enzyme (CaMKK2) was shown to decreases appetite And promote weight loss.

I found this observation odd:

They also studied both normal mice and mice missing CaMKK2 to learn how these types responded to low-fat and high-fat diets. After nearly 30 weeks on the specific diets, the normal mice on the high-fat diet became diabetic — they were unable to respond to insulin and weren’t able to manage blood sugar levels well. In contrast, the normal mice on a low-fat diet stayed healthy.

In mice missing CaMKK2, the scientists found that they stayed healthy regardless of whether they were on a low-fat or high-fat diet. The CAMKK2-negative mice apparently were protected from changes that lead to diabetes in a high-fat diet.

I don’t understand how a high-fat and presumeably low-carb thus low insulin producing diet would lead to diabetes. I’m open to suggestions. I assume we don’t have all the facts.

I suppose if the carb-content of the two diets remained the same it could make sense…?

Duke Medical News

Sleep and Hunger

Via Redtailblogger I found this interesting article that pulls together some of the relationships between eating and sleeping.

What I have long noticed is:

  • the more I eat, the more I need to sleep
  • when I suffer from lack of sleep, I lose my appetite

I’ve also long held the belief that there is a connection between longevity and sleep patterns. I’m not sure where I picked this up, but I’m sure it was reinforced by the movie The Hunger.

It seems like the link between sleep and hunger is the hormone Orexin.

The findings help explain orexin’s link to the metabolic system, the researchers said. The body is known to step up its production of orexin when blood sugar gets low. The researchers hypothesized that when a body has low blood sugar and gets hungry, the increase in orexin activates HIF-1 production, revving up metabolism so the body gets the most energy out of the sugar on hand.

Previous studies show that the absence of Orexin causes Narcolepsy (which is no fun, unless it’s your 9th grade English teacher who has in in which case life is full of great excitement).

None of this actually explains my observations… but they are getting there.

Alzheimer’s and Living Low Carb

The Washington Post reports on the correlation between “pre-diabetes” (high blood sugar levels not yet in the diabetic range) and alzheimer’s:

People with elevated blood sugar levels may have an increased risk of developing Alzheimer’s disease, researchers reported yesterday at an international conference. Scientists already have linked Type 2 diabetes with Alzheimer’s, which afflicts 4.5 million Americans.

Full Article

So what can you do to protect yourself? Go low carb of course… well at least according to Dr. Larry McCleary, the author of  The Brain Trust who describes ketones as “the brain’s preferred fuel.”
Via Living La Vida Low Carb 

Is Homocysteine Innocent?

Despite homocysteine levels being lowered by up to 30 per cent there was no effect on cardiovascular disease. “The homocysteine hypothesis is dead. It seems that homocysteineis an innocent bystander,” said Bønaa. Results also showed there was a 40 per cent increase in the risk of new cancers in the group taking folic acid (p=0.08), an observation warranting further investigation. Bønaa said: “It’s believed that folic acid may speed up the division of cancer cells.”

In a bit of old news recyled from 2005, this press release indicates that treating homocysteine levels has no impact on mortality from cardiovascular disease.

Previous studies had suggested that folic acid and vitaminB-6 exerted a beneficial effect on cardiovascular disease through their ability to lower blood levels of the amino acid homocysteine, thought to cause endothelial damage. This led some clinicians to prescribe B vitamins to their cardiovascular patients.

After three and a half years, results showed no difference for the primary end point of non-fatal/fatal MI and non fatal/fatal stroke between groups taking folic acid, vitamin B-6 and placebo. However, there was a 20 per cent higher risk of MI and stroke in the group taking folic acid and vitamin B-6.

The original 2005 presentation and comments are available on the website of the European Society of Cardiologists.

Homocysteine would thus be much like cholestorol: when present it’s a signal to get your act together but simply eliminating the substance from your bloodstream is pointless. It is a symptom and not the cause. The cause is your body out of balance from previous diet and lifestyle choices.

Endurance Training Can Age You

Training is no guarantee of health – Mark Sisson at slow twitch

Thinking of doing aerobics for the rest of your life to get in shape? The experience of endurance trainers is a useful guide:

Let’s get one thing straight right off the bat: Endurance training is antithetical to anti-aging. So it amazes me when guys in their 40s and 50s who are training for a marathon or Ironman suggest that doing so will keep them young. It won’t. You may feel like a stud now with your shaved legs and your magic marker biceps tattoos, but endurance training speeds up the aging process almost as fast as watching TV, drinking sodas and eating potato chips. Actually, in some cases, it speeds it up even faster.

There appears to be two pathways to adrenal exhaustion (which was discussed in the recent post on insulin resistance) – through consuming high GI meals (the way of the fat) or by endurance training (the way of the lean):

(…) not only does training and racing tend to produce [cortisol], but even the training meals can produce it. A meal high in sugar and other simple carbohydrates can cause a dramatic rise in cortisol (as part of an insulin-adrenaline cascade). That’s one reason why sugar is known as a powerful immune suppressor.

Chronic high-level training naturally depletes glycogen, which causes the body to release the adrenal hormone cortisol to cannibalize muscle tissue in order to help make new glucose (gluconeogenesis). Besides tearing down valuable muscle, chronic cortisol release carries with it a litany of negative effects. It suppresses immune function, which opens the door not only for short term upper respiratory infections, but may leave the door open for longer term, more serious issues (asthma, cancer, heart disease [which we know has a strong inflammatory component]). Chronic cortisol release also reduces calcium uptake by bones, and it’s not surprising that so many runner/triathletes — especially women — have low bone density. Anti-aging experts will tell you that among elderly, low bone density is a pretty accurate predictor of mortality. Break a hip bone when you’re older and your chances of dying skyrocket.

OK heavy stuff. So what does the author recommend as an ideal fitness program?

I prefer hiking, sprinting and weight-training today.

Neurotransmitters and Insulin Resistance

Discussion on adrenal exhaustion and the changes in other hormones as insulin resistance develops.

“This is not a lifestyle disorder. You can’t just tell people to try harder.”

The Link: Neurotransmitters and Insulin Resistance (8.7Mb 1h14min)
Warning – Highly Technical

From Sanesco
Sanesco International is a research-driven medical company whose goal is to expand knowledge of the body’s Communication System and its critical role in health.

Addiction, Food and Your Brain

Mounting evidence shows that compulsive eating and drug abuse engage some of the same brain circuits in similar ways, offering a new angle for understanding and treating obesity. In an interview with Scientific American, Nora D. Volkow, director of the National Institute on Drug Abuse and a pioneer in the study of addiction, explains. Full Article

Extract:

In the brains of both drug addicts and obese people we typically find a reduced number of D2 dopamine receptors in the striatum, compared to non-abusers and non-obese controls, respectively. Perhaps these findings reveal that the brain is somehow trying to compensate for the repeated surges inn dopamine stimulation from continuous stimulation with drugs or food. Another possibility is that these individuals had lower numbers of receptors to begin with, a biological feature that may put them at increased risk for diseases of addiction, in general. Low numbers of D2 receptors are well documented in people addicted to cocaine, alcohol, opiates and other drugs. Interestingly, a study by Dr. Gene Jack Wang and colleagues found the same type of relationship between the availability of D2 receptors and Body Mass Index (BMI) in obese individuals. In other words, the more obese a person is, the fewer receptors they have. By contrast, in normal weight subjects, the levels of D2 receptors are not associated with their BMI.

Are particular foods more reinforcing than others? Why?
Yes, absolutely. High calorie foods—particularly foods that are high in fat or sugar—are more likely to trigger compulsive eating. Again, that makes sense from nature’s perspective. As hunters, we didn’t always succeed at finding something to eat and so high-calorie foods, which pack a lot of energy, offered a survival advantage. In that environment, it was in our best interest to consume as much of this type of food as we could find. So they are very reinforcing. But today when we open up our refrigerators, we have a 100 percent chance of succeeding at finding food.

Our genes have changed little, but in our environment, we are now surrounded by high-fat, high-sugar foods. And this abundance is undoubtedly a major factor contributing to the rise in obesity Conditioning responses are incredibly powerful with food: when I go past a vending machine and I see chocolates I like very much, I desire the chocolate even though I’m not hungry. But if those chocolates weren’t there, it would be the last thing on my mind.

Are certain people at greater risk for drug or food addictions?
We know from twin studies that approximately 50 percent of the risk for both addiction and obesity is genetic. But the genes involved come into play on many different levels—from differences in the efficiency with which we metabolize drugs (or food) to differences in our likelihood of engaging in risk-taking or exploratory behaviors to more specific risks, such as the underlying sensitivity of the reward system.

In obesity, some people may be at a greater risk for compulsive eating because they may be overly sensitive to the rewarding properties of food. One study showed that some obese people have increased brain activity in response to mouth, lip and tongue sensations. For them, eating may be much more pleasurable than other natural reinforcers. Likewise, some people are not very efficient at registering or responding to internal signals of satiety, so they are possibly going to be more vulnerable to cravings triggered by food cues in their environment.

Does the overlap between addiction and obesity reveal any new targets for treatment?
There are pharmacological interventions to explore, such as medications that increase the dopamine response in the brain. Rimonabant, which boosts dopamine levels by dampening the endocannabinoid system, has shown promise in helping people who are obese and those who are smokers.

Another exciting development is the recent synthesis and preliminary testing of an orally administered drug that blocks orexin, a peptide that reinforces the “high” associated with drinking alcohol and is thought to regulate feeding. This drug could be extremely helpful in the treatment of specific brain disorders that involve aberrant food and drug taking behaviors.

But one of the major and distinct obstacles for a person trying to recover from compulsive eating is the obvious fact that you have to eat in order to survive whereas, if you are addicted to an illegal substance, you are in a way protected by the fact that that drug is not going to be environmentally available everywhere. One of the therapeutic interventions for drug addicts is to teach them to avoid places associated with their habit. But how do you do that with food? It’s impossible.

And these people suffer. In rats, it has been shown that, if you give them very high-sugar diets and then make them give them an opioid antagonist (naloxone), you can trigger a withdrawal that is similar to that you observe when you give naloxone to an animal that has received repeated injections of morphinel. This indicated that chronic exposure to high sugar diets generated physical dependence.

Addiction is not a choice. It is a reflexive response. Do you think that Pavlov’s dogs had a choice of salivating when they heard the sound that had been conditioned to the meat? They did not and had you seen inside their brains you would probably have observed that the sound would trigger dopamine increases in their striatum that would be signalling to expect the reward of the meat. The message that you get when dopamine is liberated in striatum—in this case, the dorsal striatum—is that you need to get into action to achieve a certain goal. It is a powerful motivator. It is extremely hard to overcome these impulses with sheer willpower.