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#394583 - 05/24/10 12:58 AM Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut
jroc Offline
Decorated_AS_Kicker

Registered: 10/30/08
Posts: 728
Loc: New Zealand
Note: Leptins and lectins are nothing to do with each other. It is an unfortunate coincidence that they only have 1 letter seperating them and that they can both play a role in AS. Leptin is a hormone in the body. Lectins are glycoproteins that are found in foods. I have included links of studies for anyone who is interested in reading them.

Leptin

Leptin is a hormone that regulates body fat. It also signals to the brain that the body has had enough to eat. Obese people produce more leptin and can become leptin resistant. This happens when leptin levels are very high in the body but the message isn't getting through to the leptin receptors. Triglycerides can interfere with leptin receptors. High fructose corn syrup increases leptin resistance and increases triglycerides in rats. A diet higher than 60% carbs can also increase triglyceride levels. Rises in blood sugar from consuming sugar or high GI carbs increases the level of insulin, triglycerides, and leptin. Lectins such as wheat lectin have the ability to bind to leptin and insulin receptors through glycosylation and it is possible that they may contribute to leptin and insulin resistance. Eating a high grain,high GI carb, high sugar diet often leads to obesity and leptin resistance.

What does leptin actually do apart from regulating fat and signialling satiety?
Leptin has other important roles in the body. “New research is revealing that glucose and therefore insulin levels may be largely determined by leptin. Leptin, through the brain and hypothalamus, also controls thyroid levels and body temperature. It largely determines the accumulation of visceral fat and the ability to burn fat as indicated by triglyceride levels. It appears to control all of the other markers of longevity.” - http://www.diabeteshealth.com/read/2008/...nge-bedfellows/

High leptin levels are a risk factor for many diseases. "Leptin has a the potent effect on T cell mediated intestinal autoimmunity and may have a role in the development of such diseases" - http://gut.bmj.com/content/53/7/921.extract

Leptin levels in AS

Many studies show increased leptin levels in AS patients.

"Our results shows that leptin production is increased and its stimulation of PBMCs significantly increased the production of pro-inflammatory cytokines in patients with active AS, suggesting its pro-inflammatory effect in pathogenesis of AS."
- http://www.ncbi.nlm.nih.gov/pubmed/19059800

"Results: At baseline, patients with AS had significantly elevated serum levels of leptin, leptin adjusted for BMI (leptin/BMI), TNF&#945;, and IL&#8208;6, but not IFN&#8208;&#947;, as compared to the controls. Serum leptin/BMI levels correlated well with IL&#8208;6 levels, and both leptin/BMI and IL&#8208;6 levels correlated well with BASDAI and CRP levels in patients with AS. The changes in leptin/BMI and IL&#8208;6 levels between the baseline and follow&#8208;up measurements correlated well with one another (p<0.05) and both correlated well with the changes in BASDAI (p<0.05).
Conclusion: Serum leptin/BMI levels were increased and significantly associated with IL&#8208;6 levels and disease activity in men with AS, suggesting a possible role for leptin in the inflammatory reactions of AS."
- http://informahealthcare.com/doi/abs/10.1080/03009740600991760?journalCode=rhe

"Leptin may be considered as a therapeutic target in some clinical situations, such as proinflammatory states or autoimmune diseases, to control an excess of immune response, as well as in other clinical situations, such as starving, to control an excess of exercise, or immune deficiencies, to improve the impaired immune response. That is why the investigation of the role of leptin in the regulation of the immune response remains a challenge for the future."
- http://www.hindawi.com/journals/mi/2010/568343.html

There is one study that on a quick read of the abstract appears to conclude that people with AS have lower leptin concentrations than controls. This study found lower leptin levels in AS patients (but with a catch). They excluded subjects with hypertension, diabetes, hyperlipidemia, and obesity! In other words, those who were most likely to have elevated leptin. In the skinny AS'ers they still found significant correlations between percent body fat, body mass index, leptin, age, and BASMI (p&#8201;<&#8201;0.05; r&#8201;=&#8201;0.6, 0.75, 0.35, &#8722;0.41, respectively). Body fat percent, waist-to-hip ratio, C-reactive protein, and BASMI were significantly correlated with serum leptin levels (p&#8201;<&#8201;0.05; r&#8201; =&#8201;0.75, &#8722;0.42, &#8722;0.52, &#8722;0.47, respectively). The surprising thing was that leptin levels were lower in the AS patients than in the controls (Did they screen the AS patients for obesity but not the controls?) They concluded that the "Chronic inflammatory condition in AS may be responsible for the reduced body fat content and lower circulating leptin concentrations." - http://www.springerlink.com/content/v543723054j4pm87/

So after exluding AS patients that were likely to have high leptin levels, still finding a correlation between leptin levels, CRP, and disease activity, they then conclude (despite numerous other trials concluding the opposite) that the inflammatory process of AS may decrease body fat and leptin levels! I don't know how some of these people manage to keep their medical researching jobs.

Leptin levels also correlate to disease activity in RA, MS and other autoimmune diseases. Fasting reduces leptin levels which has been shown to help RA and MS, and some people on this site with AS report improvement through fasting. “In rheumatoid arthritis (RA) patients it was reported that fasting leads to an improvement of clinical and biological measures of disease activity, which was associated with a marked decrease in serum leptin ... we assessed serum leptin levels in RA and osteoarthritis (OA) patients and found a correlation between serum leptin level and other markers as well as bone mass density changes, activity of disease, disease duration and the age of the patients.” - http://www.springerlink.com/content/pq7143019wm6578n/

It should be noted that elevated leptin does not cause AS by itself. Inflammatory cytokines such as TNF-a do not take aim at the joints without being prompted to by the immune system. What high leptin levels do is create a tendency for the immune system to produce more inflammatory Th1 cytokines such as TNF-a. Increased leptin is a risk factor for AS, and can excacerbate the inflammatory response in someone who already has AS, but it is not the root cause of AS.

I'll finish up on leptin by quoting a study which concludes that “immune-mediated disorders such as autoimmune disorders are associated with increased secretion of leptin and production of proinflammatory, pathogenic cytokines. Leptin could represent the "missing link" among immune response, metabolic function, and nutritional status” - http://www.ncbi.nlm.nih.gov/pubmed/18552206

Vitamin D

Low Vitamin D is associated with many autoimmune diseases. It is known to be an important regulator of immune function and gene expression. One way in which it influences the immune system is by regulating leptin levels. High doses of vitamin D lower leptin levels. People in more extreme northern/southern lattitudes get less vitamin D because there is less sunlight. Wearing sunscreen prevents vitamin D synthesis by the body.

Putting it all together

High leptin levels are bad for inflammatory autoimmune disease. High leptin levels correlate to high CRP which is a measure of inflammation. Leptin and insulin are highly intertwined. The best way to get your leptin and insulin levels through the roof is to eat a high grain, high sugar diet. Not only will this create elevated leptin but the metabolism of sugar is nutrient intensive so you chew through some of your bodies vitamin and mineral stores at a greater rate. A high grain, high sugar diet is also a good way of getting an unhealthy balance of gut bacteria or intestinal dysbiosis.

One way to keep leptin levels in check is with vitamin D. Even though the main source of vitamin D comes from the sun it is still affected by dietary factors. The addition of wheat bran to the diet has been shown to increase Vitamin D depletion.

What dietary measures could help reduce leptin levels? A low sugar/carb diet, not too dissimilar to the low starch diet that many people with AS have found to be successful. A low starch diet may be useful but may not be entirely necessary. Some cultures do not have high leptin levels despite a high carb diet. Not consuming sugar helps, so does avoiding vegetable oil and getting starches from a low lectin source such as sweet potatoes. Also foods like sweet potatoes have a lower glycemic index and so don't cause a rapid rise in blood sugar which increases leptin and insulin. It seems to be a high carb diet from grains which are high in lectins that causes problems and perhaps not the carbs/starch themselves.

Factoring the gut into the equation


Not everyone with high leptin and low vit D developes autoimmune disease. What is also required is increased intestinal permeability, otherwise known as a leaky gut. Studies on AS patients show increased gut permeability.
- http://www.ncbi.nlm.nih.gov/pubmed/4032403
- http://www.ncbi.nlm.nih.gov/pubmed/8019793
What they do not show is a direct relationship between the degree of permeability and CRP, ESR and disease activity. However we know that some people with AS do not show any increase or decrease in CRP or ESR regardless of disease activity. Now factor in leptin levels which have been shown to be directly related to CRP and increase inflammatory cytokines. Also note that ESR measures agglutination in the blood and that dietary lectins can cause agglutination in the blood. Neither gut permeability, CRP, or ESR by themselves are accurate measurements of disease activity. However by factoring in leptin levels, dietary lectin intake, and gut permeability might help explain some of these discrepancies . (If you subscribe to the starch/kleb/molecular mimicry theory then you can also factor starch intake and the amount of klebs in the gut into the equation).

The influence of lectins on gut health and leptin levels

Lectins that are found in grains, dairy, beans, legumes and some other foods are capable of
a) binding to insulin receptors, contributing to insulin resistance
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC433288/
b) binding to leptin receptors, contributing to increased leptin levels
- http://www.ncbi.nlm.nih.gov/pubmed/17983356
c) binding to and damaging intestinal villi - “soy bean lectin is able to disrupt small intestinal metabolism and damage small intestinal villi via the ability of lectins to bind with brush border surfaces in the distal part of small intestine.”
http://en.wikipedia.org/wiki/Lectin
d) preventing the repair of already damaged epithelial cells
http://en.wikipedia.org/wiki/Lectin
e)increasing abnormal stimulation of the immune system towards gut bacteria.
http://www.livingglutenfreecaseinfree.com/articles/inflammation/food-lectins-in-health-and-disease/
f) accelerating depletion of vitamin D stores
- http://www.ncbi.nlm.nih.gov/pubmed/62993...Pubmed_RVDocSum
(note: it could be grain fibre that does this and not lectin)

Needless to say that is a very bad combo as far as autoimmune inflammatory disease is concerned. It is worth noting that the lectin content of food is highly dependent on the way that it is prepared and that some lectins are worse than others and that some can even be beneficial.

Summary

Leptin – Increases inflammatory cytokines such as TNF-a which play a crucial role in autoimmune inflammatory arthritis.
Factors that increase leptin – sugar, grain and lectin intake
Factors that decrease leptin – vitamin D, low sugar, low carb diet

Vitamin D – good for immune system. decreases leptin levels.
Factors that increase vitamin D - sunshine exposure, food intake e.g salmon
Factors that decrease vitamin D – wearing sunscreen, high/low latitudes, wheat bran

Lectins – May contribute to leptin and insulin resistance, known to cause gut damage.
High intake from a diet high in grains, dairy, beans, legumes.
Levels can be reduced by proper preparation techniques including soaking, fermenting and thorough cooking. Some sugars (often marketed as glyconutrients) such as glucosamine can bind to lectins and render them harmless.

Gut health – Damaged villi prevent nutrient interception and absorption. Increased permeability of epithelium initiates the exposure of gut bacteria to the immune system (abnormal antigen presentation) that is suspected to trigger the autoimmune process. (Note: Infections outside the GI tract can also initiate an autoimmune reaction such as Chlamydia in Reiter's Syndrome)
Factors that can damage villi and increase permeability – Lectins, NSAID's, Caffeine, Alcohol, Food allergy/intolerance, Bacterial dysbiosis, Stress, Physical injury/trauma.

If this was theory was somewhere in the ball park we would expect to find a high prevalence of autoimmune disease in ...
a) countries where grains and sugar make up a high percentage of calories.
b) northern (or southern) latitudes that get less sunlight
c) in places where people live highly stressed lifestyles and commonly consume gut irritants such as caffeine/alcohol/NSAID's

Anyone know of any countries like this with obesity and autoimmune epidemics?

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#394590 - 05/24/10 01:58 AM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, [Re: jroc]
Sue22 Offline
Very_Addicted_to_AS_Kickin

Registered: 01/13/08
Posts: 20633
Loc: Upstate NY
thanks for this, good info!

Originally Posted By: jroc
Anyone know of any countries like this with obesity and autoimmune epidemics?


not a clue! wink2
_________________________


sue

Spondyloarthropathy, HLAB27 negative
Humira (still methylprednisone for flares, just not as often. Aleve if needed, rarely.)
LDN/zanaflex/flector patches over SI/ice
vits C, D. probiotics. hyaluronic acid. CoQ, Mg, Ca, K.
chiro
walk, bike
no dairy (casein sensitivity), limited eggs, limited yeast (bread)

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#394603 - 05/24/10 05:15 AM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut [Re: jroc]
Gerri Offline
Colonel_AS_Kicker

Registered: 04/22/06
Posts: 2371
Loc: Kitchener, Ontario Canada
I find this information very informative, and have printed it out for myself.

Gerri

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#394606 - 05/24/10 08:07 AM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut [Re: Gerri]
Alinus Offline
Ninja_AS_Kicker

Registered: 01/09/10
Posts: 839
Loc: Romania, Suceava
an excelent post jroc. as always !
_________________________
34. Some rheumys say AS stage 1-2 some others say USpA
Also UC - rectocolitis.

UC curently in remission since feb 2011.
AS/USpA remission march-aug 2011. Flare - sept-nov 2011 (antibiotics). Remission now...

Modified NSD/SCD. Cook your own !
____________________________________________________________
Mesalazine-Salofalk 500 mg/day

And the list of my medication has become verry short after some years on this diet smile

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#394871 - 05/25/10 06:10 PM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut [Re: Alinus]
neilwilson Offline
Apprentice_AS_Kicker

Registered: 04/28/10
Posts: 97
Loc: berkshire england
whats pig weed

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#394873 - 05/25/10 06:21 PM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut [Re: neilwilson]
jroc Offline
Decorated_AS_Kicker

Registered: 10/30/08
Posts: 728
Loc: New Zealand
weed that has been confiscated by the police.

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#394913 - 05/26/10 12:07 AM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut [Re: jroc]
Alinus Offline
Ninja_AS_Kicker

Registered: 01/09/10
Posts: 839
Loc: Romania, Suceava
nop smile

Atriplex hortensis - in latin.

maybe the translation was not a good one hehe.
_________________________
34. Some rheumys say AS stage 1-2 some others say USpA
Also UC - rectocolitis.

UC curently in remission since feb 2011.
AS/USpA remission march-aug 2011. Flare - sept-nov 2011 (antibiotics). Remission now...

Modified NSD/SCD. Cook your own !
____________________________________________________________
Mesalazine-Salofalk 500 mg/day

And the list of my medication has become verry short after some years on this diet smile

Top
#394947 - 05/26/10 05:11 AM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut [Re: Alinus]
lifeworks Offline
New_Member

Registered: 05/25/10
Posts: 2
excellent report! I do wellness coaching and this is primo important when dealing with the diabetes, RA, fibromyalgia, IBS, etc.... I was thinking it was more to do with the lectin/leptin response (and it is), but you showed more importantly the impact of the sugars we consume. A pharmacist client says it's all about the sugars. She got off the HighFructose after her studies and she knows that's one major key. And yes, I do know of another country with high autoimmune, obesity, high inflammation, U.S.A!!
where the new government diet is far away from understanding the impact of gluten, very disturbing.
anyway, thanks for the post, excellent!

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#394949 - 05/26/10 06:07 AM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut [Re: lifeworks]
jroc Offline
Decorated_AS_Kicker

Registered: 10/30/08
Posts: 728
Loc: New Zealand
thanks. i've been looking into a bit of different dietary stuff recently from a few different angles such as things like ensuring adequate vitamin and mineral intake, minimising anti-nutrients such as phytic acid, avoiding common allergens, lectins, gut health, antioxidants, inflammation, cholesterol ratio, leptin, weight loss, immune system balance etc and it seems that from almost every angle you come at it from you end up with the same old suspects - sugar, grains, dairy, seed oils.

those foods aren't going to cause any major issues if eaten occasionally but when you start getting a high percentage of your calories from grains, dairy, sugar and seed oils it seems to increase the risk of many health problems. on the other hand if you base your diet around vegetables, fruit and meat then it seems to be hard to go too far wrong in any of those categories.



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#394951 - 05/26/10 06:09 AM Re: Connecting dots: Leptin, Vit D, TNF-a, Lectin, Gut [Re: jroc]
kurumi Offline
Superior_AS_Kicker

Registered: 09/01/08
Posts: 955
Loc: The Batcave
V interesting.... thanks for that. Going to look at some of those links you've posted. It has been a wee while since I've done some light wink reading.
_________________________
"Traveler, there is no road, you make your path as you walk." - Antonio Machado

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