Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
(find topics using search [upper left] or index [lower right]), and
more articles by Prof. Ayers on Suite101 .

Monday, July 20, 2015

HELLP, Preeclampsia, Antiphospholipid Antibodies and Basic Triplets

—-the other 200 posts —-
Clotted RBCs in Capillary
Some of my research involves the unique properties of milk and the development of the immune system, so I talk to medical people, lactation researchers and occasionally discuss the control of inflammation involved in ovulation, fertilization, implantation, gestation, labor and lactation.  It is clear to me that there are a few trends in disruption of these pregnancy processes resulting from the modern increase in inflammation and gut-related problems linked with immune tolerance.  Infertility is increasing, because women are becoming more chronically inflamed.  Miscarriages and premature births/low birth weight are increasing, because chronic inflammation enhances labor.  Pre-eclampsia (high blood pressure and protein leaking into the urine) results from chronic inflammation and omega-3 fatty acid depletion.  Now an even scarier form of pre-eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) is on the rise.  I want to discuss HELLP to put all of these pregnancy-related problems into perspective.

HELLP, Cause and Cure Unknown?
HELLP is an autoimmune disease and I have repeatedly discussed the cause of autoimmune diseases:  1) inflammation, 2) deficiency of Tregs (immune tolerance) and 3) antigen basic triplets (antigen presentation).  When HELLP was recently brought to my attention with a sudden rise in local hospitals, I decided to see if it could be easily explained and cured, just by examining the available medical literature.  Wikipedia indicated that the cause and cure was not known and that was confirmed by local doctors, who just treat the symptoms by early deliveries and long stays for the babies in neonatal intensive care units.  My work was cut out for me.

Autoimmune Disease with Unknown Autoantigen 
An examination of the symptoms, rupture of blood cells (fibrin production), liver damage, clotting (low serum heparin), high blood pressure (capillary apoptosis), proteinuria (low heparan sulfate (HS) to prevent protein loss), pointed to some obvious treatments and the causes.  Infertility is often treated by in vitro fertilization/insemination, supported with aspirin and heparin injections to maintain gestation.  These treatments are consistent with high levels of chronic inflammation that block implantation and stimulate labor.  Infertility is also associated with antiphospholipid antibodies.  A closer look at the antiphospholipid antibodies showed that they were directed against β2-glycoprotein-I.  So, I expected the β2-glycoprotein-I protein to be the original target for the antibodies, the initiating antigen, but when I looked up the sequence of that protein, it lacked the expected basic triplet I have found in all  other autoantigens and allergens.  This meant to me that there was a different protein with a related sequence that started the HELLP autoimmune disease.

Attack on P-Selectin Starts Immune Autoimmunity
I checked for other proteins with related sequences and basic triplets (RKR in the carboxy terminal sequence below), and found P-selectin that is produced most abundantly in liver and on the surface of blood cells.  A quick search of the literature showed that P-selectin reacts with anti-phospholipid antibodies and has a pair of basic triplets that enhance immune presentation and make this protein a strong candidate for becoming an autoantigen.  Antibodies against P-selectin will cause clotting as seen in HELLP.

ref|NP_002996.2| P-selectin precursor [Homo sapiens]:

Antibiotics and Liver Damage
I suspect that HELLP is caused by a combination of liver damage and prior exposure to antibiotics (or common drugs that have antibiotic activity) that cause gut dysbiosis, i.e. loss of gut bacteria that stimulate development of the suppressive part of the immune system, e.g. deficiency in regulatory T cells, Tregs.  Examples of the type of liver damage that may lead to HELLP are excessive consumption of alcohol (alcoholic fatty liver) or high fructose corn syrup (non-alcoholic fatty liver).

HELLP from Cause to Cure

  • Diet and/or infection causes liver inflammation.
  • Antibiotics/drugs and/or processed foods lacking prebiotic fiber produce gut dysbiosis.
  • Lack of gut bacteria needed for development of the immune system in the gut produces a deficiency of Tregs and dysfunction of immune tolerance.
  • Liver inflammation, deficiency of Tregs and availability of antigens with basic triplets leads to antibodies against liver proteins.
  • Chronic inflammation leads to decrease in HS production and leaky kidneys/proteinuria.
  • Chronic inflammation/liver damage produces fibrin production.
  • Fibrin production and low HS enhances clotting and leads to apoptosis/cell death in capillaries.
  • Loss of capillaries leads to high blood pressure.
  • Cure of HELLP, anti-phospholipid antibodies and pre-ecampsia, involves lowering chronic inflammation (aspirin and heparin treatment) with an Anti-Inflammatory Diet, fixing vitamin D deficiency, increasing omega 3/6 ratio,  and repairing gut dysbiosis to fix immune tolerance.
  • Without these interventions, HELLP symptoms will become more severe, especially in subsequent pregnancies and additional autoimmune diseases will develop.


Anna said...

You just provided me with answers to my unanswered questions. I had a healthy boy after 5 miscarriages. He was conceived after I adopted a paleo lifestyle. I didn't really understand why. Nor did I get why morning sickness and the sheer inability to eat the right way led to me feeling as ill I ever have in my life. I know now why my asthma and joint pains floored me in pregnancy. Those nine months were tough and if I'd known what you've just told me in five mins I'd have made myself eat those veggies. This little man almost didn't make it. He's got immense strength, and forever I'll be teaching my family the right way to eat because of what you've taught me. Thank you.

Anonymous said...

Always interesting to read this blog even if the science is more often than not beyond me. Like a lot of people who read these posts, they've probably arrived here trying to find a solution to ill health that their doctors have failed to solve. In my situation I have had both chronic rhinitis which gives me nocturnal headaches and a generalised inflammation in the pelvic area, never properly diagnosed beyond being told that I have "Pelvic pain syndrome". 15 years of burning, ED and headaches is no fun! As I trawl the net looking for advice one comes across all sorts of suggestions for good health. Prof Ayers protocol is one. My question is how can we know that this is correct? For example I recently came across Dr McDougal's "Starch Solution", a low protein, very low fat, very high starch diet. Anecdotally, many people have responded well to this diet, losing weight (not a problem for me, I am skinny) and more interestingly for me, finding long standing health issues, including inflammation, improving to the point of cure. This diet is at odds with the suggestions of Prof Ayers that starch should be extremely limited if not avoided. The science all seems very murky to me. I remain confused. Tom

william duffin said...

Hi Dr Ayers

I read with interest your recent comments on Tim's blog, and I don't know if you noticed in the earlier comments or not, that I've been trying to treat ankylosing spondylitis with potato starch, inulin and psyllium alongside soil based probiotics for the last 2-3 months - mainly based upon your recommendations in your curing autoimmune and allergies post.

I'm assuming the fact that the above approach has resulted in a worsening of my symptoms therefore indicates that my gut flora is in pretty poor shape at this point in time. Is there anything additional - to following a low starch diet and eliminating the usual trigger foods/increasing fermented vegetables - that you could suggest, with particular focus on lowering klebsiella whilst increasing the healthy bacteria species at the same time?

Many thanks

Dr. Art Ayers said...

The first two things to do are to fix your vitamin D: test, supplement and retest until you are at least in the mid range.
Make sure that you don't have any dental/oral infections or sources of inflammation.

Check that you are following my guidelines for The Anti-Inflammatory Diet on my blog.

Most soil based probiotic supplements don't have Clostridium butyricum, so check.
Besides the diet, what are the sources of bacteria that you are using to replace the bacteria missing in your gut? What about hygiene, family, pets, gardening?

Dr. Art Ayers said...

I know little about Dr McDougal's "Starch Solution". It just seems like an adaptation of Tim's potato diet. If you have the gut flora to adapt to the prebiotic fiber that is presented, then the resultant improvement in gut flora diversity should produce health benefits. If not, then the vegetables will just make your gut uncomfortable and your symptoms will be the same or worse. I didn't see any provision for or mention of gut flora. The emphasis on a vegan diet isn't to me supported by the literature for general use. It requires gut flora adapted to vegetable prebiotics and rapid development of functional biofilms to avoid vitamin deficiencies.

I don't try to provide any medical treatments. I just try to explain what is happening in sickness and health. I communicate my understanding of the science literature and hope that is helpful. I am not selling vegetarian food or health resort stays.

I don't think that starch should be eliminated or drastically reduced, but I do find wheat flour a potential problem. I think that Mark Sisson has wise guidelines on his site. I merely try to provide the insight that all of the blood sugar needed for minimal survival can be provided by the liver from dietary protein. Starch is normally a simple dietary inclusion, but for people with diabetes, for example, it is much easier to reduce starch consumption. Carbohydrates in the form of prebiotic fiber is essential, however, to feed gut flora. So low carb can make sense, if it just means low starch, but it should never mean low dietary fiber.

Thanks for your questions.

Anonymous said...

Thanks for your reply Dr Ayers.

william duffin said...

Hi Dr Ayers

I've been taking a 5000iu vitamin D tablet for the last few years, but haven't actually ever had my levels tested so I'll look into getting this done. The UK climate certainly doesn't help with regards to vit D levels either.

As far as other bacterial sources go - I was taking the Probiotic 3 for a month in May, followed by a month of Prescript Assist and I'm now a week or so into Primal Defence Ultra. As good as these products are, I dare say that any benefits have been adversely affected however, by my taking large amounts of PS, inulin and psyllium powder when my gut wasn't ready for this,

I do follow your anti-inflammatory diet guidelines, except for the fermented vegetables part, so this is something that I really need to focus on from here on in. Hopefully this shall be the missing link in repairing my gut flora.

Thanks again

antonio sabarro jr said...

FMT is the answer

Anonymous said...

Anonymous said...

Dr Art,

not sure if you have seen this:

Missing link found between brain, immune system; major disease implications

Natasha said...

Hello! I just wanted to share this recently published article. Researching T1D, microbiome and antibiotic use. Testing it out on mice.

My husband is still struggling with his collection of autoimmune diseases. Which likely has a great deal to do with the fact that his mother never breatfed, raised him on canned milk and he had easy access to antibiotics.

Anonymous said...

Dr Ayers

Nebivolol.....a beta blocker , has been shown to make significant decreases in endothelial dysfunction, partly by inhibiting P Selectin.

I am not advocating Nebivolol except it is an approved treatment for HTN, which happens to restore vasculars dysfunction through production of NOS and inhibition of adhesion and other signaling molecules.

I'll post the article when I get a chance.

Anonymous said...

Celik T, Iyisoy A, Kursaklioglu H, et al. Comparative effects of nebivolol and metoprolol on oxidative stress, insulin resistance, plasma adiponectin and soluble P-selectin levels in hypertensive patients. J Hypertens. 2006;24:591–6. [PubMed]

Dr. Art Ayers said...

I don't get the point of trying to address hypertension by playing with beta blockers. It seems to me that hypertension is a symptom of the breakdown of capillaries beds via chronic inflammation. Thus, fiddling with salt or NO to lower blood pressure, just seems to be bypassing the homeostatic mechanisms rather than fixing the problem of inflammation. I leave complex symptoms to doctors and try to address causes and related cures, which have simpler solutions.

Natasha said...

Dear Dr. Ayers,

I read something recently. T-reg treatment for humans.

They are taking T-reg from "recently" diagnosed T1D, multiplying them in the lab and then infusing them back to the patient. They say that it lasts for one year - no injected insulin is then needed (no insulin or little insulin, it is not clear).

I am pretty excited. My husband has T1D and Sarcoidosis. All autoimmune. As you might guess, he was raised on baby formula. :-( This allowed him to physically grown up, but he has had nothing but immune system problems. I digress...

News article:

Dr. Bluestone USC profile:

Bluestone Lab Research

Would like to know your thinking on it. Does it seem like a reasonable treatment?

Kind regards,

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Anonymous said...

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Anonymous said...

I am thankful for the article.Really looking forward to read more

Anonymous said...

Hi Dr Ayers -

I accidentally stumbled on this post about HELLP after you were listed on this site:

EVERY symptom you mentioned was what I went thru while trying to get pregnant and after going on the GAPS diet, I finally was able to conceive and delivered a baby boy. But, my pre-eclampsia was so bad along with rising blood pressure at an alarming rate during the delivery that the side effects of epidural actually was a life-saver for me.

I'm so grateful for your post and to finally understand what was going on in my body. NO ONE was able to connect the dots for me.

You are, indeed, the BEST! Keep it up!!


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