Insulin Resistance: Leptin and Lectins

by Catherine M. Haug,  August 2007; updated April 2021 [note: red text indicates updates/changes yet to be made]

Leptin is a hormone that signals:

• satiety–sense of fullness–as a signal to stop taking in food; and 
• hunger when fuel storage drops below a ‘set point.

To a certain extent, release of insulin into the bloodstream is controlled by leptin. It is possible for cells to become resistant to leptin as well as to insulin (in fact, cells can also become resistant to other hormones, but that is not the topic here). Refer to Insulin Resistance: the Leptin Connection for more.

Lectins are needed by plants to preserve the species; lectin toxicity keeps spiders, insects, birds, rodents and other animals – including humans – from eating un-sprouted seeds by making them sick. The process of germination begins to break down the lectins, removing the toxicity. By the time the young sprout produces its first leaves, the lectins are all gone until the plant’s blossom produces new seeds.

For those plant seeds whose lectins are toxic to humans, they should be removed or sprouted (to break down the lectins) before eating the plant. Tomatoes are a perfect example, as their seeds contain lectins toxic to humans. Refer to Lectins: what they are, and how to deal with them for more.

• See also (this site): 1. Diet and Health Menu*; 2. Notes on Insulin Resistance (IR); 3. Choline, Inositol, and Insulin Resistance; 4. Ketogenic Diet; 5. Cyclical Ketogenic Diet (CKD) and Metabolic Mitochondrial Therapy (MMT)

‘*See Diet and Health Menu under “Insulin, Insulin Resistance, and Metabolic Syndrome” for list of other articles about Insulin Resistance (some still need to be moved to Cat’s Kitchen)

Leptin and Lectins:

There is evidence that the lectin proteins in all plants may play a role in leptin resistance. Especially lectins in grains such as Wheat Germ Agglutinin or WGA. Also, gliadin – a component of gluten in the endosperm – has a lectin as part of the molecule). See the following for more: 

• Mercola: The Critical Role of Wheat in Human disease (1g)
• Whole Health Source articles: Leptin and Lectins Part I (8a), Part II (8b)and Part III (8c)
• Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance? (8) published in BMC Endocrine Disorders, 2005 by T. Jonsson, et. al.

The hypothesis here is that cereal lectins may bind to the leptin receptors (as they are already known to bind to insulin receptors, making the receptors insensitive to the presence of insulin. And that this binding alters leptin sensitivity, leading to weight gain.

I was curious whether sprouting the grains before consumption or grinding to flour, would break down the lectins before the grains are consumed (as sprouting is known to affect phytates and certain other enzyme inhibitors). Fermenting (as in sourdough) may also break down or neutralize lectins in grain. I sent a query to Sally Fallon (Nourishing Traditions author), who in turn sent it to Chris Masterjohn. His response (from his email):

“[Lectins] are quite definitely problematic if they are not appropriately neutralized, whether by [natural] processing of the food [fermentation, sprouting, pre-soaking] or by interception in the digestive tract.  Some lectins are broken down during cooking or other processing, some are not. 

The two main lectins in wheat are WGA in the germ and alpha-gliadin in the endosperm.  WGA is an N-acetyl-glucosamine-binding lectin and alpha-gliadin is a mannose-binding lectin.  Cooking does not neutralize either of them; long-rise sourdough culture neutralizes alpha-gliadin but I do not know about WGA.  

Both lectins can be intercepted by their respective sugars or by polyreactive or specific IgA antibodies in the digestive tract.  The sugars can be provided in the diet but also circulate in digestive secretions; their concentration in digestive secretions will vary between individuals, as will IgA antibody secretions, leading to individual differences in susceptibility to their harmful biological activity.”

Thus, sprouting certainly helps, but having a healthy intestinal mucosa is also important; as is a diet that includes the sugars that would bind to these lectins to carry them out of the body before they could be absorbed. [Cat’s note: my original sources for the following bullet items are no longer available.]

• N-acetyl-glucosamine (NAG), is not available in the diet, but must be synthesized by the body from glucose. However, it is a constituent of chitin, from which supplements can be made. It is also present in bovine and shark cartilage, neither of which are really edible. As glucosamine, it is a readily available supplement.
• Mannose is much easier to obtain in the diet. It is found in polysaccharides present in the following foods: aloe vera, fenugreek, and shiitake mushrooms, red or black currants, gooseberries, green beans, cayenne, cabbage, eggplant, tomatoes, turnips and kelp. 

Cat’s notes, April 2021: I currently take d-mannose to help keep my urinary tract healthy. I stopped taking any form of glucosamine (including NAG) because I read is not good for those with insulin resistance. However, Mayo Clinic (12) and Diabetes Library (13) articles refute that, based on more recent studies.

“Introduction to Lectin” by Jun Hirabayashi (11) offers a brief description of lectins.

Adiponectin (Hormone)

Adiponectin is another hormone involved in regulation of sugar and fat metabolism. It is produced primarily in adipose tissue, but also in muscle, and even in the brain, and circulates in the bloodstream, acting as a messenger. (4a, 14)

It increases insulin sensitivity of cells, so that they respond better to the signaling of insulin, to uptake and metabolize blood sugar.  A curiosity is that as one becomes more obese, the less the fat cells produce adiponectin; while there are theories about this phenomenom, none have been proven. (4)

This inverse relationship between obesity and adiponectin levels is especially troubling because obesity is closely tied to insulin sensitivity: as insulin sensitivity decreases, the tendency to gain weight (especially abdominal fat) increases.  This increase in abdominal fat further lowers insulin sensitivity, and a cyclic situation develops.

No one really knows which comes first: decreased insulin sensitivity or tendency to gain weight in the abdominal region.  Allopathic medicine is firmly in the camp that believes obesity and lack of exercise causes insulin resistance and leads to type-2 diabetes.  However, there is no proof of this.  Many researchers believe that something else, perhaps something in the modern diet of synthetic foods, causes the initial decrease in insulin sensitivity, thus stimulating weight gain, which then in turn further lowers insulin sensitivity.

One study suggests that “adiponectin concentrations are more closely related to differences in insulin-mediated disposal than [to] obesity.” (5)  This means that while levels of adiponectin decrease as obesity (as measured by BMI) increases, the primary effect of adiponectin is to decrease insulin sensitivity, rather than to increase fat storage.

Fat Hormones and Weight Control

In laboratory experiments on animals, administration of leptin causes weight loss by suppressing appetite and increasing metabolism.  Similar results have not been obtained with human subjects, but research continues.

When injected into lab animals, adiponectin also causes weight loss, but does not appear to affect appetite; rather, weight loss is a result of increased metabolism alone.  

Both leptin and adiponectin are made in adipose (fat) tissue, and affect glucose (sugar) and lipid (fat) metabolism by exerting their influence on the brain. (3)

Researchers, at this point, are not indicating that the fat hormones such as leptin and adiponectin will be administered as drugs for long term weight loss.  Indeed, they have not been able to produce the same weight loss by injecting these hormones into humans, as they have effected with lab animals.  But a better understanding of the weight control mechanisms may lead to new drugs for safe weight control.

In the meantime, Mary G. Enig believes that including coconut oil in the diet can be used to stimulate long term weight loss.  The medium chain fatty acids in tropical oils like coconut, have the ability to increase metabolism and to stimulate satiety, for appetite suppression.  The exact mechanism by which these effects happens is not yet known.  Another weight-benefit of coconut and other tropical oils is that the medium chain fatty acids are more readily metabolized (burned for fuel) than other, longer chain fats, because they do not need to be processed in the liver first.  This makes them an excellent source of quick energy, ensuring that they will not be converted into body fat for storage. (5) 

A Disease of Nutrition

Drs Mercola and Rosedale believe that diabetes (and insulin resistance) is a disease of nutrition, and I agree, including the dietary changes they recommend [April 2021 update].  Mercola suggests a diet devoid of starchy carbs (grains, breads, sweets), but high in vegetables (and fruits to a lesser extent), and balanced for protein and what they call “good” fats. (1a) 

“Science is telling us that we must eat a diet that maximizes the accuracy of insulin and leptin signaling allowing cells, you, to better listen to their life-giving messages. (The need for those hormones to have to “yell” to be heard is reduced and the levels of insulin and leptin are therefore lowered.)” (1a) 

I’ve not purchased their books on diet (The Rosedale Diet; Mercola’s Total Health Program), so I’m not familiar with the details, but I do think a total ban on whole grains is a little extreme; a better option is to convert to sprouted whole grains, as sprouting breaks down the lectins.  

Sally Fallon, in her book Nourishing Traditions, advises using whole grains that have first been sprouted or soaked in whey, which makes the nutrients in the grain more bioavailable, thus increasing their nutritional value. This is an ancient technique which has historical merit; traditional peoples are free of the modern diseases of nutrition by which we are so troubled.  Sprouted or soaked whole grains provide fiber which slows down the absorption of sugar, to avoid blood-sugar spikes.  They also provide enzymes, vitamins and minerals to assist in proper assimilation of the nutrients provided by the grain, as well as those provided by other foods ingested at the same time. (6) 

Mary Enig, coauthor of Eat Fat Lose Fat (with Sally Fallon) cites a need for increasing the amount of certain fats in the diet, specifically medium-chain fatty acids in fats such as coconut and palm oils, and Omega-3 fats in cod liver oil, butter (from pasture-fed cows), eggs (from pasture-fed hens), and raw dairy.  Coconut oil consumed before a meal provides many benefits, not the least of which is to incite the secretion of leptin, signaling satiety, so that one doesn’t eat too much.  Cod liver oil provides, in addition to the Omega-3 fats, vitamins A and D.  All fats slow down the rate of absorption of sugars, to avoid blood-sugar spikes; hence the importance of buttering your bread (or dipping in olive oil); of dressing your veggies with an oily salad dressing or melted butter; and of dipping fruits in creme fraiche or yogurt. (7)

See also Livestrong’s article: Adiponectin and Diet (14). As I review that article, I will add important notes here.

References, Sources:

NOTE: numbers in parenthesis, such as (1), are my old reference numbers, prior to reorganizing the list.

1. Mercola (the following are his old format which is not secure, and may no longer be available; I provide related secure links to check out instead):
   1. (1) mercola.com/2005/may/31/diabetes_disease.htm; try this instead: mercola.com/ebook/diabetes-symptoms.aspx 
   2. (2) mercola.com/2005/apr/2/leptin_diabetes.htm; try this instead: articles.mercola.com/sites/articles/archive/2014/07/14/type-2-diabetes-insulin-leptin.aspx or articles.mercola.com/sites/articles/archive/2014/01/05/dr-johnson-leptin-resistance.aspx 
   3. (3) mercola.com/2004/dec/1/leptin1.htm; try this instead: articles.mercola.com/sites/articles/archive/2010/01/28/many-ignorant-of-waist-fat-risk.aspx
   4. (4) mercola.com/2004/jun/5/obese_brains.htm; try this instead: articles.mercola.com/sites/articles/archive/2010/05/04/how-the-us-government-contributes-to-the-obesity-epidemic.aspx
   5. (5) mercola.com/2000/oct/1/leptin_sugar.htm; see reference 1B, above (with Dr. Johnson) instead. check out reference 1f, next.
   6. (6) mercola.com/2000/mar/5/exercise_lowers_fat_hormone.htm
   7. articles.mercola.com/sites/articles/archive/2010/01/16/The-Critical-Role-of-Wheat-in-Human-Disease.aspx
2. Mercola (newer format)
   1. (12) http://articles.mercola.com/sites/articles/archive/2010/01/16/The-Critical-Role-of-Wheat-in-Human-Disease.aspx
3. (7) www.1is2fat.com/fat_hormone_adiponectin.htm is no longer valid; try this: curejoy.com/content/natural-treatments-low-fat-hormone-adiponectin/
4. wikipedia:
   1. (8) en.wikipedia.org/wiki/Adiponectin
5. (9) medscape.com/viewarticle/470735
6. (10) Nourishing Traditions by Sally Fallon with Mary G. Enig, Ph.D.
7. (11) Eat Fat Lose Fat by Mary G. Enig, Ph.D. with Sally Fallon
8. (15) bmcendocrdisord.biomedcentral.com/articles/10.1186/1472-6823-5-10
9. Whole Health Source; note: as of April 2021, these are not secure:
   1. (13) wholehealthsource.blogspot.com/2008/04/leptin-and-lectins.html and
   2. (14) wholehealthsource.blogspot.com/2008/04/leptin-and-lectins-part-ii.html 
   3. (16) wholehealthsource.blogspot.com/2008/04/leptin-and-lectins-part-iii.html
10. heartspring.net/glyconutrient_sources.html; link no longer valid – heartspring.net domain is for sale
11. Glycoforum article, Introduction to Lectin: glycoforum.gr.jp/glycoword/lectin/LEA00E.html
12. mayoclinic.org/diseases-conditions/osteoarthritis/expert-answers/glucosamine/faq-20058151
13. diabeteslibrary.org/glucosamine-and-diabetes/
14. Livestrong on adiponectin and diet: livestrong.com/article/313879-adiponectin-and-diet/